Cardiology TodayCover May-June 2017 - CIMS · Dr. Monica Bhatia EDITOR IN CHIEF OP Yadava SECTION...

Cardiology TODAY

VOLUME XXI No. 3MAY-JUNE 2017

PAGES 93-128

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MANAGING DIRECTOR & PUBLISHERDr. Monica Bhatia

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EDITORIALTaxing the Vice = Good Health? 95OP YADAVA

REVIEW ARTICLEOSA and Heart Failure 97SN ROUTRAY, SASMITA SWAIN

REVIEW ARTICLEAsymptomatic Severe Mitral Regurgitation 105ROHIT TANDON, SATISH K PARASHAR

REVIEW ARTICLETake Home Messages from a Meeting on "Innovations in Thrombosis Management" Held on January 7-8, 2017 at Mumbai organized by Academy of

Cardiology (AOC 2017), www.acadcard.com 112SATYAVAN SHARMA, NIKHIL RAUT

Cardiology Today VOL.XXI NO. 3 MAY-JUNE 2017 93

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IMAGEBiventricular Hypertrophic Obstructive Cardiomyopathy in a Neonate 117SR MITTAL

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PICTORIAL CMECoronary Artery Thrombus 126MONIKA MAHESHWARI

94 Cardiology Today VOL. XXI NO. 3 MAY-JUNE 2017


Taxing the Vice = Good Health ?

EDITORIAL

That public measures and community activities work has been conclusively demonstrated by a recent study published in Journal of American Medical Association, Cardiology in April 2017.1 A lot has been said about banning transfats and adding soda taxes to reduce the consumption of sugary beverages with the aim of reducing incidence of atherosclerotic diseases. The current study demonstrated that following

cant decline in hospital admissions for myocardial infarction (MI) and strokes (Table 1). And this is when it is in effect a partial ban because this law still does not apply to the whole food industry and is applicable only to the restaurants. If the grocery products

Taking the bar next notch higher, if other ancillary measures like stimulating more physical activity and walking, control of visceral obesity and diabetes – important components of metabolic syndrome in India, too are paid due attention, virtually the landscape of cerebrovascular and coronary atherosclerosis of this country can be reversed, with consequent huge social, economic and physical impact. The additional

t demonstrated in this study, over the already downward trends of atherosclerotic

over and above other health stimulating issues like tobacco ban etc.

Table 1: Additional Decline in Outcomes in Counties with vs without a trans-fat banOutcome % (95% CI) ‘p’ Value

MI or stroke -6.2 (-9.2 to -3.2) <0.001

MI -7.8 (-12.7 to -2.8) 0.002

Stroke -3.6 (-7.6 to 0.4) 0.08

To add substance to the matter, another study published in journal PLoS Medicine2

ts of sugar tax imposed in November 2014 in

One must realize that sugar is the main reason for hypercholesterolaemia and is an addictive substance, in the same league as alcohol and tobacco. Sugar, therefore, should not be taken as a benign ingredient of diet. It’s high time that our country be cognizant of these studies and the measures introduced by other countries and follow suit. Even countries like Fiji and Mexico have levied prohibitive taxes on tobacco, alcohol and sugary beverages.

DR. OP YADAVACEO and Chief Cardiac Surgeon

National Heart Institute,New Delhi


EDITORIAL

Infact diet soda drinks are even worse culprits and have been shown to increase the incidence of strokes. In an MRI-based study,including cognitive testing, in around 4000 subjects aged 30 and above, the authors found that consuming diet soda led to poorermemory, smaller size of the lower hippocampus and overall brain volumes leading to a three times higher risk of developing strokeand dementia.3 nding was independent of the risk of developing diabetes and its role in dementia and similar associations were not found for sugar-sweetened drinks.

ned sugar with low sugar alternatives, one should better alter ones taste buds and get used to consuming less sweet food. A sweet tooth is an acquired malady and can very easily be altered specially in children. Right from the early years of life, one must be wary of inculcating the habit of high sugar consumption in infants, toddlersand children. Once rights habits are initiated and developed, they carry through rest of the life. In parallel, the industry too should be encouraged to not reduce just the sugar content, but also the sweet taste of the beverages. Unsweetened beverages should be encouraged. These broad-based community level initiatives will reap a much bigger dividend than chasing the diseases they cause.

REFERENCES1. Brandt RJ, Myerson R, Coca M et al. Hospital admissions for myocardial infarction and stroke before and after the trans-fatty acid restrictions in New York. JAMA Cardiol 2017. doi:10.1001/

jamacardio.2017.04912. Silver LD, Ng SW, Ryan-Ibarra S et al. Changes in prices, sales, consumer spending and beverage consumption one year afer a tax on sugar-sweetened beverages in Berkeley, California, US: A

before-and-after study. PLoS Med 2017;14(4):e100.22833. Pase MP, Himali JJ, Beiser AS et al. Sugar and artificially sweetened beverages and the risks of incident stroke and dementia: A prospective cohort study. Stroke 2017, Apr 20; (E Pub, Ahead

of print).


OSA and Heart Failure

REVIEW ARTICLE

SN ROUTRAY, SASMITA SWAINKeywords � ST segment elevation myocar-dial Infarction

� OSA � heart failure

Dr S.N. Routray Professor and HOD Cardiology, S.C.B. Medical College, Cuttack; Dr Sasmita Swain, Associate profes-sor O&G, S.C.B. Medical College, Cuttack

INTRODUCTIONSleep is a naturally recurring state of mind and body characterised by altered consciousness, relatively inhibited sensory activity, inhibition of nearly all voluntary muscles, reduced interaction with the surrounding and a decreased ability to react to stimuli. Physiological sleep plays an important role in maintaining good physical and mental health. It promotes normal growth and development improves memory, help maintain a healthy balance of hormones and immune system. Prior to early 1920s, scientists regarded sleep as an inactive brain state; however modern research has shown that brain is quite active, many formative works are designed and damages are repaired during sleep. Six to eight hours of sleep in a day is essential. Chronic sleep deprivation leads to increase in BMI and obesity (particularly central obesity), risk of hypertension, diabetes, cardiovascular disorders,

depression and stroke. 20% of US adults are affected by insomnia but only 10% are chronic. One 38 year longitudinal study of 1409 adults, concluded that persistent, but not intermittent insomnia, was associated with increased all-cause and cardiopulmonary mortalities and steeper increase in infl ammatory markers.1

Sleep disordered breathing, particularly obstructive sleep apnea (OSA) is an emerging important public health problem worldwide including India.2 Awareness among public and primary care health personnel is very low in India. OSA is common among obese individuals, children and post menopausal women. It is usually associated with co-morbidities such as metabolic syndrome, diabetes mellitus, hypertension, stroke, coronary artery disease, heart failure and various psychiatric disorders.

OSA is caused by repetitive collapse of upper airways that leads to snoring, frequent episodes of sleep interruption,

AbstractWorldwide sleep disordered breathing, particularly obstructive sleep apnea (OSA) is an emerging important public health problem including India. In this article we intended to cover the entire spectrum of the disease starting from the prevalence, defi nition, classifi cation, diagnosis, pathogenesis, clinical features, treatment approaches.


hypoxemia, hypercapnia, swings in intra-thoracic pressure, surges in sympathetic nervous system activity and blood pressure and frequent awakenings, all of which many have adverse cardiovascular consequences.3 Prevalence of OSA in heart failure (HF) is very common however, there is no defi nite evidence suggesting any causal relationship. Management of OSA needs a long term multidisciplinary approach. Once diagnosed, patient and family members should be counselled to manage their illness including co-morbidities through their active partitipation.

DEFINITION, CLASSIFICATION AND DIAGNOSISApnea is defi ned as complete cessation of respiration for 10 seconds or more. If it is during sleep, it is sleep apnea. Sleep apnea due to central cause is called central sleep apnea (CSA) and due to obstruction of pharyngeal airway is called obstructive sleep apnea (OSA). In OSA respiratory (ventilator) effort persists during apnea which is not present in CSA. Obstructive hypopneas are decreases in ventilation (reduction of tidal volume of 50% to 90%, lasting more than 10 seconds) associated with fall in oxygen saturation (≥ 3%

decrease in oxyhemoglobin saturation)or terminated by arousal from sleep. A diagnosis of OSA is accepted when a patient has apnea-hypopnea index (AHI) i.e, no. of apneas and hypopneas per hour of sleep more than 5. If it is associated with

excessive daytime sleepiness (EDS) or at least two episodes of choking or gasping during sleep it is called obstructive sleep apnea syndrome (OSAS)4,5,6 (Figure 1, Table 1).

Severity of OSA is graded according to AHI (mild: AHI 6-14, moderate: 15-29 and severe: 30 or more). While judging severity, degree of sleep disturbance and oxygen desaturation are also to be considered.

OSA is usually confi rmed by overnight polysomnography in a sleep laboratory during which sleep architecture (apnea, hypopnea etc), cardiac rhythm, SaO2, airfl ow and thoracoabdominal movements are recorded. Because of limited availability of polysomnography, portable cardiorespiratory monitoring devices have been developed for home screening and diagnosis of OSA. However, many different devices are on the market, several of which have not undergone rigorous validation, particularly in the HF population. Therefore, more research is required to demonstrate their validity in HF patients.7

PATHOGENESIS OF OSAMultiple factors are responsible for

REVIEW ARTICLE

Table 1 - Definition of termsTERM DEFINITION

Apnea Cessation of airflow for > 10 s

Hypopnea A reduction in but not complete cessation of airflow to < 50% of normal,

usually in association with a reduction in oxyhemoglobin saturation

AHI The frequency of apneas and hypopneas per hour of sleep : a measure of

the severity of sleep apnea

OSA and hypopnea Apnea or hypopnea resulting from complete or partial collapse,

respectively, of the pharynx during sleep

CSA and hypopnea Apnea or hypopnea resulting from complete or partial withdrawal of

central respiratory drive, respectively, to the muscles of respiration

during sleep

Oxygen desaturation Reduction in oxyhemoglobin saturation, usually as a result of an apnea or

hypopnea

Sleep apnea syndrome At least 10 to 15 apneas and hypopneas per hour of sleep associated

with symptoms of sleep apnea, including loud snoring, restless sleep,

nocturnal dyspnea, headaches in the morning, and excessive daytime

sleepiness

Polysomnography Multichannel electrophysiological recording of electroencephalographic,

electroculographic, electromyographic, ECG, and respiratory activity to

detect disturbance of breathing during sleep

NREM sleep Non–rapid eye movement or quiet sleep

REM sleep Rapid eye movement or active sleep; associated with skeletal muscle

atonia, rapid movements of the eyes, and dreaming

Arousal Transient awakening from sleep lasting <10s

Figure 1. Normal, partial and complete airway obstruction resulting in hypopnea and apnea, respectively.


pathogenesis of OSA with inter-individual variation. OSA patients have repeated narrowing or obstruction of pharyngeal airway during sleep. It has been suggested that pathophysiological mechanisms, such as anatomic compromise, pharyngeal dilator muscle dysfunction, lowered arousal threshold, ventilatory control instability and /or reduced lung volume tethering are the pathophysiological mechanisms leading to OSA.

Patients with OSA generally have a narrow pharynx related to fat accumulation in the neck that compromises the pharyngeal lumen. During sleep, loss of pharyngeal dilator muscle tone causes complete or partial pharyngeal collapse resulting obstructive apneas and hypopneas, respectively.10

Although OSA probably contributes to the development or progression of HF, HF might also contribute to causation of OSA. According to this view, fl uid accumulation in the legs while upright during the day could shift into the neck when recumbent during sleep. Such fl uid displacement might cause distension of the neck veins and/or oedema of the peripharyngeal soft tissue that increases peripharyngeal tissue pressure, predisposing to pharyngeal obstruction. Overnight rostral fl uid displacement from the legs contributes to the severity of OSA by causing fl uid accumulation in the neck that narrows the pharynx and increases its collapsibility during sleep. The volume of fl uid displacement is related to sedentary living and leg oedema. Nevertheless, whether OSA precedes or arises secondary to HF, once present, it is likely to provoke adverse cardiovascular effects.

Night-to-night variations in rostral fl uid displacement may help to explain some of the internight variability in the AHI that has been described in OSA patients without HF. Therefore, alterations in volume status in HF patients might also be accompanied by alterations in the AHI. However, there are few data on night-to-night variability of AHI in patients with HF.

Both OSA and CSA are common in patients with HF and can coexist in the same patient,11 and the predominant type can change over time.12 Data from

the CANPAP (Canadian continuous Positive Airway Pressure for patients with heart failure and central sleep apnea) trial demonstrated a spontaneous conversion from predominantly CSA to predominantly OSA in 18% of subjects in the control arm in association with an improvement in left ventricular ejection fraction (LVEF).13 If the improvement in LVEF was accompanied by decreased fl uid retention and overnight rostral fl uid shift, this might be one mechanism through which this conversion occurred.

PATHOPHYSIOLOGY OF OSAPathophysiologic effects and

consequences are given schematically (Figure 2).

CARDIOVASCULAR EFFECTS OF OSAEffects of sleep Normally, metabolic

rate, sympathetic nerve activity (SNA), BP, and heart rate (HR) decrease, and cardiac vagal activity increases during non-rapid eye movement (REM) sleep. Although intermittent surges in SNA, BP, and HR occur in REM sleep, in general, the average BP and HR remain below

Figure 2. Schematic outlining proposed pathophysiological components of OSA, activation of cardiovascular disease mechanisms, and consequent development of established cardiovascular disease.

Table 2. Pathophysiologic consequences of OSA


waking levels. Thus, sleep is characterised by cardiovascular quiescence. However, this is disrupted by OSA with potentially adverse consequences. In addition, patients with HF have sleep approximately 1.3 h less than subjects without HF, and may not enjoy fully the restorative effects of sleep.7

Mechanical effects. During obstructive apneas, negative inspiratory intrathoracic pressure generated against the occluded pharynx increases LV transmural pressure, and hence afterload (Figure 3).14 It also increases venous return, augmenting right ventricular (RV) pre-load, whereas OSA induced hypoxic pulmonary vasoconstriction increases RV afterload. Consequent RV distension and leftward septal displacement during diastole impairs LV fi lling. This combination of increased LV afterload and diminished preload reduces stroke volume and cardiac output more in HF patients than in healthy subjects. Whereas stroke volume recovers abruptly to baseline in

healthy subjects at apnea termination, recovery is delayed in patients with HF. Increased LV transmural pressure also increases myocardial oxygen demand while simultaneously reducing coronary blood fl ow during which apnea-related hypoxia reduces oxygen delivery.15 This can precipitate myocardial ischemia and impair cardiac contractility and diastolic relaxation.7 Over time, such stresses may contribute to development or progression of cardiac remodelling, hypertrophy, and failure.

Autonomic effects. Intermittent hypoxia and CO2 retention stimulate central and peripheral chemoreceptors that augment SNA. Apnea also enhances SNA by eliminating refl ex inhibition of SNA arising from pulmonary stretch receptors. Reductions in stroke volume and BP during obstructive apneas unload carotid sinus baroreceptors and refl exively augment SNA. This is exaggerated in patients with HF. Arousal from sleep at apnea termination also augments SNA

and reduces cardiac vagal activity that precipitates post-apneic surges in BP and HR. These adverse autonomic effects of OSA may persist into wakefulness.16

VASCULAR ENDOTHELIAL EFFECTSIntermittent hypoxia and post-apneic reoxygenation induce oxidative stress, generate reactive oxygen species, and provoke infl ammation. Reactive oxygen species diminishes nitric oxide levels and hence, impairs endothelially mediated vasodilation that could contribute to development of hypertension. Patients with OSA have low plasma nitrite concentrations and attenuated endothelium-dependent vasodilatation.

Reactive oxygen species can also activate nuclear transcriptional factors, including nuclear factor-kappa B (NF-kB), which stimulates production of infl ammatory mediators such as tumor necrosis factor-α interleukin [IL]-6, IL-8, and C-reactive protein, as well as adhesion molecules such as intracellular and vascular cell adhesion molecules, E selectin, and CD15.17 Such effects could facilitate endothelial damage and atherogenesis. Nonrandomized studies reported that treatment of OSA by CPAP lowered levels of several infl ammatory mediators, and a randomized trial demonstrated that treatment of OSA by CPAP reduced carotid intima-media thickness, supporting a cause–effect relationship between OSA and atherosclerosis.18 Therefore, promotion of coronary atherosclerosis, the commonest cause of HF, is another means by which OSA could contribute to the development of HF.

ARRHYTHMOGENIC EFFECTS Although epidemiological studies have not demonstrated an increased prevalence of bradyarrhythmias in OSA, apnea induced hypoxia can provoke atrioventricular block and asystole that is reversible by atropine or treatment of OSA. These observations demonstrate a role for OSA in their causation. Compared with subjects without OSA, those with severe OSA are more likely to have AF, nonsustained ventricular tachycardia, ventricular bigeminy, and trigeminy. Several studies showed that OSA predicts

REVIEW ARTICLE

Figure 3. Effects of OSA on the RV and LV. During obstructive sleep apnea (OSA), negative intrathoracic pressure generated against the occluded upper airway (UA) increases left ventricular (LV) transmural pressure (intracardiac minus intrathoracic pressure) and LV afterload. It also increases venous return, augmenting right ventricular (RV) pre-load, whereas OSA-induced hypoxia causes PA vasoconstriction and pulmonary hypertension. These cause RV distension and leftward displacement of the interventricular septum during diastole, which impairs LV filling and diminishes LV pre-load and stroke volume. PA =pulmonary artery; + = positive intracardiac pressure; - = negative intrathoracic pressure.


new-onset AF or its recurrence following cardioversion to sinus rhythm.

In a randomised trial, treatment of OSA by CPAP in patients with HF reduced the frequency of nocturnal ventricular ectopy. In HF patients with cardioverterdefi brillators, device discharges occurred more frequently in patients with than those without sleep apnea, particularly during sleep time, suggesting a link between OSA and nocturnal malignant arrhythmias.19

EPIDEMIOLOGY AND CLINICAL FEATURES OF OSA AND HFIn US 24% of adult men and 9% of adult women have OSA (AHI > 5); and 4% of adult men and 2% of adult women have OSAS (AHI>5+EDS). Community based epidemiological studies from several parts of India have estimated that the prevalence of OSAS is 2.4 to 4.96% in men and 1 to 2% in women.20 However 85% of patients with clinically signifi cant and treatable OSA have never been diagnosed, and referred population of OSA patients only represent the tip of the iceberg.

Data from the Sleep Heart Health Study showed that OSA with an AHI ≥ 11 was independently associated with 2.38 relative odds of having HF.5 Hypertension is likely an intermediate step between OSA and HF. Nondippers have greater risk for LV hypertrophy and failure than dippers. Since OSA causes nondipping of BP at night, it may contribute to this increased risk. Other factors, described above, may also contribute to the development of HF.

Several polysomnographic studies in HF patients reported prevalences of OSA (12% to 53%) higher than in the general population.11,21 Risk factors for OSA in patients with HF include older age, male sex, and greater body mass index (BMI).11 Compared with the general population, in whom AHI increases as a function of BMI, HF patients have lower BMI for any given AHI, with a much weaker correlation between AHI and BMI. Consequently, factors other than obesity, such as nocturnal rostral fl uid displacement, must play a greater role in the pathogenesis of OSA in the HF than in the general population.22

In patients with HF, OSA is more common in men than in women,11 and most are habitual snorers. However, compared with the general population, HF patients with OSA complain of hypersomnolence less often, and have lower Epworth Sleepiness Scale scores at any given AHI.22 In contrast to the general population, there is no signifi cant relationship between the Epworth score and increasing AHI. Furthermore, for any given AHI, patients with HF have a longer sleep-onset latency, and less sleep than the general population despite being less sleepy.22 (For detail risk factors, warning symptoms and screening tools the tables at the end of the chapter may be referred)

Untreated severe OSA patients (AHI >30) had higher cardiovascular mortality, independent of presence of absence of HF.7 Patients with ischemic HF are more susceptible to the adverse effects of apnea-related hypoxia, elevated SNA, and/or cardiac arrhythmias, possibly related to

worsening of myocardial ischemia, than those with nonischemic HF.23 In contrast, Roebuck et al. did not fi nd increased mortality associated with OSA in patients with HF.24 However, since they did not analyse separately those with treated and untreated OSA, conclusions are diffi cult to draw.

Prevalence of OSA in HF: In a systematic review by Krawczyk et al in 2013, prevalence of OSA is about 50% in heart failure, however, moderate to severe OSA (AHI> 15) was detected in 20% of heart failure patients.25 In one large series OSA was detected in 37% of 450 patients with HF26. In men, the main risk factor for OSA was obesity, whereas in women it was older age.26 In another prospective study by Wang et al. The prevalence of OSA was 26%.27 OSA also has been noted in >50% of heart failure patients with preserved systolic function.28 Three months of CPAP improved the diastolic function suggesting a potential etiologic role of OSA in diastolic heart failure.

OSA & progression of heart failure: The most important direct mechanism by which longstanding OSA might induce LV systolic dysfunction is by raising blood pressure. Increased sympathetic outfl ow, increased LV afterload and hypoxia may also contribute to LV dysfunction. OSA patients have higher production of cytokines, catecholamines, endothelin and other growth factors and can contribute to ventricular hypertrophy independent of hypertension.

Adrenergic activation increases myocardial oxygen demand at time of recurrent hypoxia. Consequent metabolic mismatch can directly reduce myocardial contractility. These stress may place the patients with OSA with HF at greater risk of myocardial ischaemia, worsening ventricular function, arrhythmia and death.

However, it is yet to be established whether OSA can cause HF. In addition whether the presence of OSA in HF accelerates mortality remain unclear.

TREATMENT OF OSA AND HF

Treatment of HF, effects on OSA:-Theoretically treatment of HF results in decrease of intravascular volume and

What symptoms should prompt consideration of OSA?OSA can affect anyone, but is more common in some people, including those who:

• snore

• intermittently stop breathing when sleeping

• are male and middle aged

• are a woman past menopause

• are overweight or obese

• have a large neck size (17 inches or more)

• have a small airway

• have a set-back or small lower jaw

• have large tonsils

• have a large tongue

• have an abnormal face shape, or nasal blockage

• have a medical condition that make some of these factors more likely, such as Down’s

syndrome.


attenuation of venous congestion, thereby could potentially reduce OSA severity. However there is no systematic evidence that treatment of HF (general measures and specifi c drugs) have any direct effect on severity of OSA,29 apart from an increase in AHI reported in the setting of a cough and airway infl ammation with angiotensin converting enzyme inhibitors.30

Recently in one prospective an observational study involving patients with optimally treated HF, prevalences of OSA, and CSA were unchanged over a 7 year period despite increasing use of beta-blockers and spironolactone during that time.11 These fi ndings suggest that these drugs have little effect on prevalence of OSA in stable HF patients.

In one study after 7 months of cardiac resynchronization therapy in 13HF patients with OSA, the AHI decreased signifi cantly (p = 0.04) in association with a reduction in circulation time.31 In contrast, Oldenburg et al.32 reported that in HF patients after 5 months of cardiac resynchronization therapy, whereas the AHI fell in patients with CSA, it did not change in patients with OSA. In another uncontrolled trial, the AHI decreased by 30% in 8 HF patients with OSA following a 4-month exercise program.32 However, none of these studies examined the effect of interventions on nocturnal fl uid displacement. In addition, because of their uncontrolled nature, results of these studies are inconclusive. Accordingly, randomised trials are needed to determine whether, and by what mechanisms, treatment of HF can alleviate OSA.

Treatment of OSA, effects on HF: OSA patients are advised to reduce weight and to abstain from alcohol and sedatives that predispose to pharyngeal collapse during sleep; these general measures may reduce the severity of heart failure and the severity of OSA. No pharmacologic treatment has been found to be benefi cial. Oral devices may be helpful in some cases. Currently, the treatment of choice in OSA is positive airway pressure (PAP) therapy. Three types of PAP devices are available for treatment of OSA: continuous PAP (CPAP), bi-level PAP (BPAP), and automatic self-adjusting

PAP (APAP). CPAP is considered the gold standard treatment and is indicated in moderate to severe OSA and mild OSA with symptoms or co-morbidities. There have been no controlled studies of mandibular advancement devices or upper airway surgery involving OSA patients with heart failure. Bariatric surgery to reduce morbid obesity has been tried in some cases.

CPAP acutely alleviates OSA, abolishes intrathoracic pressure swing and reduces nocturnal BP and heart rate, thereby results in reduction of LV afterload. The fi rst study to examine the effects of CPAP on left ventricular function during the awake state was uncontrolled. Eight patients with idiopathic dilated cardiomyopathy and coexisting OSA were studied. After 1 month of CPAP, mean left ventricular ejection fraction increased from 37% to 49% and dyspnea was reduced signifi cantly34 but these responses dissipated within a week of withdrawal of CPAP. In the fi rst randomised trial involving 24 patients with heart failure (mean left ventricular ejection fraction < 45%) and moderate to severe OSA (mean AHI > 20), 30 days of CPAP lowered daytime heart rate and systolic BP and increased ejection fraction by 9%. In contrast, there was no change in any of these variables in the 12 patients in the control group.35

In a second larger randomised cohort with heart failure (mean left ventricular ejection fraction< 55%) and OSA (mean AHI> 5), there was a more modest 5% increase in ejection fraction after 3 months of CPAP treatment in the 71% of randomized patients who completed this trial.36 Mean BP did not fall. It is notable, however, that a third randomised study, and the only one that used a crossover design, showed no effects of autotitrating CPAP compared with subtherapeutic

CPAP on peak V O2, 6-minute walk distance, plasma catecholamines, or left ventricular ejection fraction, although there was a decrease in daytime sleepiness.37 Recent observational data suggest a trend (p=0.07) to a lower mortality rate in heart failure patients with CPAP treated OSA compared with untreated OSA.27

Two nonrandomised observational studies addressed the effects of treating OSA on morbidity and mortality in HF patients. In the fi rst, there was a trend to lower mortality in the 14 who accepted CPAP than in the 37 who did not (p = 0.007) over 2.9 years.27 In the second involving 88 HF patients with OSA, hospitalisation-free survival was signifi cantly greater in the 65 CPAP-treated patients than in the 23 untreated patients over 2.1 years.38 Although promising, these results are not conclusive due to the nonrandomised nature of the studies and their small sample sizes.

In the recently published SAVE trial,39 which randomised 2717 eligible adults between 45 and 75 years of age who had moderate to severe obstructive sleep apnea and coronary or cerebrovascular disease to receive CPAP treatment plus usual care(CPAP group) or usual care alone (usual-care group). The primary composite end point was death from cardiovascular cause, myocardial infarction, stroke or hospitalisation for unstable angina, heart failure or transient ischemic attack. Secondary end points included other cardiovascular outcomes, health related quality-of-life, snoring symptoms, daytime sleepiness and mood.

Most of the participants were men who had moderate-to-severe obstructive sleep apnea and minimal sleepiness. In the CPAP group, the mean duration of adherence to CPAP therapy was 3.3 hours per night, and the mean apnea–hypopnea

American Academy of Sleep Medicine (AASM) recommendations for surgical treatment of OSA• If non-invasive types of therapy have not worked or are rejected by the patient

• Tracheostomy is the only operation shown to be nearly 100% effective as a sole procedure

for OSA.

• UPPP (Uvulopalatopharyngeoplasty) is indicated for retropalatal obstruction.

• For retrolingual (type II and III), mandibular maxillary advancement is the most promising

(>90%) surgical approach.

• Role of bariatric surgery for weight management is not well defined.

REVIEW ARTICLE


1.10; 95% confi dence interval, 0.91 to 1.32; P = 0.34). No signifi cant effect on any individual or other composite cardiovascular end point was observed. CPAP signifi cantly reduced snoring and daytime sleepiness and improved health-related quality-of-life and mood.

The evidence in the preceeding text suggests that, just as in the non-

HF population, the main indication for treating OSA in HF patients in hypersomnolence, where treating OSA reduces sleepiness and improves QOL.36 However, most HF patients with OSA are not hypersomnolent.22 In such patients, indications for treating OSA have not been clearly defi ned. Adequately powered randomised trials will be required to assess whether treating OSA in nonsleepy HF patients improves cardiovascular outcomes.

Ongoing clinical trials such as the ISAACC study (Clinical Trials. gov number, NCT01335087) will shed further light on the effect of CPAP in nonsleepy patients with obstructive sleep apnea and acute coronary syndromes. Furthermore, although improving CPAP technology to maximize adherence is important, we believe that there is also a need for novel treatment options that allow for better adherence.

CONCLUSIONOSA is a common chronic disorder which is often unrecognized. Prevalence of moderate to severe OSA in HF is around 20%. It is independently associated with increased risk of death of any cause. Direct causal relationship of OSA with HF is not established. OSA has adverse cardiovascular effects and is associated with reduced survival in patients with HF. At present CPAP along with general measures is the treatment of choice, though there is symptomatic improvement, long-term benefi cial effect is not well proven. Future research will throw more light on disease understanding and provide more effective management options.

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Table II. Risk factors for obstructive sleep apnoeaDemographic characteristics

Older age

Male gender

Pregnancy

Risk factors linked to OSA by strong published evidence

Obesity

Central body fat distribution

Neck circumference

Anatomical abnormalities of the craniofacial region and upper airway specific syndromes

(e.g., Treacher-Collins syndrome, Pierre Robbins syndrome)

Retroposed mandible/maxillae, hypertrophied tonsils, tongue

Other suspected (potential) risk factors

Familial aggregation

Tobacco smoking

Menopause

Alcohol use

Night time nasal congestion

Endocrine abnormalities: hypothyroidism/acromegaly

Polycystic ovarian syndrome

Down’s syndrome

Drugs e.g., benzodiazepines, muscle relaxants, testosterone therapy

index (the number of apnea or hypopnea events per hour of recording) decreased from 29.0 events per hour at baseline to 3.7 events per hour during follow-up. After a mean follow-up of 3.7 years, a primary end-point event had occurred in 229 participants in the CPAP group (17.0%) and in 207 participants in the usual-care group (15.4%) (hazard ratio with CPAP,

Who should be screened for OSA?All adults who answer yes to either question:

� Are they dissatisfied with their sleep?

� Do they have daytime sleepiness?

Patients with risk factors

� Obesity, especially BMI >35 kg/m2

� Family history of obstructive sleep apnea

� Retrognathia

� Treatment-resistant hypertension

� CHF, atrial fibrillation, stroke

� Type 2 diabetes

Patients with high-risk driving occupations or daytime sleepiness + motor vehicle crash

What are the screening tools?Berlin questionnaire (primary care setting)

� 10 items

� Snoring severity, significance of daytime sleepiness, witnessed apnea, obesity, hypertension

STOP-BANG screening test (preoperative setting)

� 8 items

� STOP: Snoring, Tired, Observed apnea, high blood Pressure history

� BANG: elevated BMI, Age > 50, increased Neck circumference, Gender male

Neither tool precludes formal sleep testing


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12. Tkacova R, Wang H, Bradley TD. Night-to-night alterations in sleep apnea type in patient with heart failure. J Sleep Res 2006;15:321-8.

13. Ryan CM, Floras JS, Logan AG, et al. Shift in sleep apnoea type in heart failure patients in the CANPAP trial. Eur Respir J 2010;35:592-7.

14. Bradley TD, Hall MJ, Ando S, Floras JS. Hemodynamic effects of simulated obstructive apneas in humans with and without heart failure. Chest 2001;119:1827-35.

15. Bradley TD, Floras JS. Sleep apnea and heart failure: part I: obstructive sleep apnea. Circulation 2003;107:1671-8.

16. Somers VK, Dyken ME, clary MP. Abboud FM. Sympathetic neural mechanisms in obstructive sleep apnea. J Clin Invest 1995;96:1897-904.

17. Gravey JF, Taylor CT, McNicholas WT. Cardiovascular disease in obstructive sleep apnoea syndrome: the role of intermittent hypoxia and inflammatory. Eur Respir J 2009;33:1195-205.

18. Drager LF, Bortolotto LA, Figueiredo AC, Krieger EM, Lorenzi GF. Effects of continuous positive airway pressure

on early signs of atherosclerosis in obstructive sleep apnea. Am J Respir Crit Care Med 2007;176:706-12.

19. Serizawa N, Yumino D, Kajimoto K, et al. Impact of sleep disordered breathing on life threatening ventricular arrhythmia in heart failure patients with implantable cardioverter defibrillator. Am J Cardiol 2008;102:1064-8.

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22. Arzt M, Young T, Finn L, et al. Sleepiness and sleep in patients with both systolic heart failure and obstructive sleep apnea. Arch Intern Med 2006;166:1716-22.

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27. Wang H, Parker JD, Newton JE, Floras JS, Mak S. Chui KL, Ruttanaumpawan P, Tomlison G, Bradley TD. Influence of obstructive sleep apnea on mortality in patients with heart failure. J Am Coll Cardiol. 2007;49:1625-1631.

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32. Oldenburg O, Faber L, Vogt J, et al. Influence of cardiac resynchronization therapy on different types of sleep disordered breathing. Eur J Heart Fail 2007;9:820-6.

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36. Mansfield DR, Gollogly NC, Kaye DM, Richardson M, Bergin P, Naughton MT. Controlled trial of continuous positive airway pressure in obstructive sleep apnea and heart failure. Am J. Respir Crit Care Med 2004;169:361-366.

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Asymptomatic Severe Mitral Regurgitation

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ROHIT TANDON, SATISH K PARASHARKeywords � mitral regurgitation � LV ejection fraction � effective regurgitant orifi ce area

� color fl ow mapping � PISA

Dr. Rohit Tandon is Senior Consultant Physician, Dayanand Medical College & Hospital, Unit Hero DMC Heart Insti-tute, Ludhiana; Dr. Satish K Parashar is Senior Consultant Cardiologist & Director, Non-Invasive Cardiac Laboratory, Metro Hospital & Heart Institute, New Delhi

AbstractMitral regurgitation ( MR ) is one of the commonest valvular disorders encountered in routine clinical practice with estimated prevalence of around 2-3% in general population. While a careful history and physical examination remain essential in the overall evaluation of patients with MR, echocardiography is essential for establishing the aetiology, mechanism, hemodynamic consequences, assessment of severity, and timing of intervention in asymptomatic severe MR. However in doubtful cases, a stress echo may be helpful to unmask symptoms.Corrective surgery is indicated only in selected patients with asymptomatic severe chronic MR. As such it is imperative to assess if MR is severe. Echocardiography has emerged as one of the leading non-invasive diagnostic technique in assessing severity. Doppler and colour fl ow mapping provide various semiquantitative and quantitative criteria to assess severe MR. Some of the important criteria of severity include (a) Regurgitant jet area >40-50% of LA (b) Vena contracta width >7.0 mm (c) Proximal Isovelocity Surface Area (PISA) or Flow Convergence, details have been mentioned in the text (d) Pulmonary vein Doppler: In severe MR, the systolic jet impinges on systolic wave of pulmonary vein causing systolic fl ow reversal in more than one vein. Systolic blunting is suggestive but not specifi c for signifi cant MR (e) Regurgitant orifi ce area: which is a fundamental measure of severity. A value ≥0.40 cm2 indicates severe MR of a primary aetiology. Some other methods include regurgitant volume and fraction. It is also important to have knowledge of role of stress echocardiography, three dimensional echocardiography, strain parameters, in improving upon the risk stratifi cation. Irrespective of echo Doppler grading, severe chronic MR does not exist (with rare exceptions) without clear evidence of left atrial or


when the annulus is calcifi ed leading to MR. Annulus is dilated if it is >35 mm or > 21mm/m2

• Infective cause like endocarditis or perforation of the leafl et (Figure 3)

• Rupture of chorda tendineae (Figure 4)

• Congenital causes like cleft mitral valve, Parachute mitral valve, Atrio - ventricular canal defects, Hypertrophic obstructive cardiomyopathy (Figure 5)

MECHANISMS OF MITRAL REGURGITATIONCarpentier classifi cation depicts various mechanisms based on leafl et apparatus abnormality leading to mitral regurgitation is shown below:

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INTRODUCTIONMitral regurgitation ( MR ) is one of the commonest valvular disorders encountered in routine clinical practice with estimated prevalence of around 2-3% in general population. While a careful history and physical examination remain essential in the overall evaluation and management of patients with suspected MR, diagnostic methods are often needed and are crucial to assess the aetiology and severity of MR, the associated remodelling of cardiac chambers in response to the volume overload, and the optimal timing of intervention.

CLASSIFICATION OF MITRAL REGURGITATIONMR is basically classifi ed as (a) Primary or organic MR which is due to a structural or degenerative abnormality of the mitral valve apparatus (b) Secondary or functional MR in which the mitral valve is structurally normal. It is mainly due to regional and global remodelling of the left ventricle, which interferes with the function and integrity of the mitral valve apparatus. This classically includes ischemia due to coronary artery disease , dilated cardiomyopathy and any condition leading to mitral annular dilatation like atrial fi brillation, restrictive cardiomyopathy etc. The signifi cant LV remodelling leads to apical displacement of papillary muscles, thereby pulling one or both mitral leafl ets apically leading to incomplete closure of leafl ets and MR. In this article we shall keep our focus of discussion mainly on primary mitral regurgitation.

AETIOLOGY OF CHRONIC PRIMARY MITRAL REGURGITATIONThe functional components of mitral valve apparatus comprise of the following:

� Mitral annulus � Mitral leafl ets � Chordae � Papillary muscles � Left ventricular myocardium

underlying the papillary musclesA lesion in any of the components can lead to MR. As such some of the common causes of primary MR, as encountered in daily practice, include the following:1. Infl ammatory causes: Rheumatic

heart disease, Systemic Lupus, drugs2. Degenerative causes: Myxomatous

degeneration like mitral valve prolapse, (Figure 1, 2) isolated or associated with Marfan syndrome, Ehlers-Danlos syndrome. Mitral annulus calcifi cation – a normal mitral annulus contracts by about 25% in systole. This is deranged

left ventricular enlargement. If the left ventricular end-diastolic dimension (by echocardiography) is less than 60 mm, (approximately 35 mm/m2), the diagnosis of severe chronic MR should be seriously questioned. Left atrial size may refl ect the severity and duration of chronic MR and degree of LA complianceThe various criteria for surgery in severe asymptomatic MR have been discussed. A brief review of percutaneous techniques and mitral valve repair is mentioned.

Figure. Carpentier classification depicts various mechanisms


Asymptomatic severe MR: Understanding of following factors is extremely important in relation to the title of the paper:

� Natural history of MR � Is the patient really asymptomatic � In doubt can stress test be of help in

unmasking symptoms � Criteria for severe MR � Functional state of LV & management

issues : Repair vs replacement

NATURAL HISTORYNatural history of MR depends upon volume of regurgitation, myocardium state, and aetiology. Rapid progression is expected in connective tissue diseases, such as Marfan’s syndrome, than in those with chronic MR of rheumatic origin. In asymptomatic severe MR patients, the rate of progression to symptoms, LV dysfunction, pulmonary hypertension or AF is 30% to 40% at 5 years. All studies uniformly indicate that asymptomatic patients with severe MR and normal left ventricular functions have high likelihood of requiring surgery over the next 5 to 10 years and long-term survival after successful surgical repair of primary

MR is reduced in patients with even mild preoperative symptoms compared to those who had undergone surgery when they are completely asymptomatic. These considerations have prompted recommendations for earlier surgery in patients who are candidates for repair. Enriquez et al calculated 5 year survival and mortality rates in asymptomatic patients with severe MR based on ERO and concluded 58±9% survival rate and 36±9% risk of cardiovascular mortality over 5-years in patients having asymptomatic MR with ERO>40 mm2.

IS THE PATIENT TRULY ASYMPTOMATIC?Patients of severe MR may remain asymptomatic due to compensatory mechanisms and a dilated compliant LA. As mentioned earlier, a careful history is extremely important as sometimes patient’s involuntarily limit their activity to create an asymptomatic state. In an exhaustive study, though pertaining to asymptomatic severe aortic stenosis, Pai etal reported that 4% of patients with LV ejection fraction (LVEF) of < 20%, 12% with LVEF of about 30% or less and

10% with pulmonary artery pressure of > 60mm Hg. claimed no symptoms. As such due importance should be given in eliciting symptoms. According to AHA /ACC 2014 guidelines on valvular heart disease, classifi cation of primary mitral regurgitation, asymptomatic severe mitral regurgitation falls into stage C which is further divided into C1 and C2 stages. This defi nition includes consideration of valve anatomy, valve hemodynamic and its hemodynamic consequences as assessed by echocardiography and symptoms due to pathophysiological changes brought about by the lesion. The criteria of severity are discussed below:

Confi rmation of asymptomatic status ‒ Is there any role of stress echocardiography?Stress echocardiography although class 2A recommendation, is very useful in elucidating symptoms in patients who are otherwise deemed to be asymptomatic. 20% of asymptomatic severe MR patients exhibit sub-maximal functional capacity on cardiopulmonary exercise testing and have lower event-free survival despite good LV function and normal LV dimensions. Exercise capacity (lower than 100% age/sex predicted (METs) achieved), heart rate recovery (heart rate response <18 beats within 1 min after exercise) after stress, EROA of more than 13 mm2 during exercise, increase in EF <4%,increase in LV end systolic volume >25 ml/m2 ,increase in global longitudinal strain <2% are markers of adverse outcome, poorer symptom-free survival and worse outcomes after

Figure 1. Left sided image shows mitral valve prolapse of posterior leaflet with partially flail leaflet. Right sided image shows eccentric jet of MR

Figure 2. Shows value of transesophageal echo showing mulltiscallop MV prolapse with three jets ofMR . On transthoracic echo a single jet of MR was seen

Figure 3. Shows perforation of anterior mitral leaflet (arrowed) in a case of left atrial myxoma with infective endocarditis. LA: left atrium, LV: left ventricle, MV: mitral valve

Figure 4. Flail anterior mitral (arrowed) with the whole leaflet prolapsing in LA including tip

Figure 5. A case of hypertrophic obstructive cardiomyopathy showing systolic anterior motion of anterior mitral leaflet (vertical arrow). The interventricular septum (IVS) shows asymmetrical septal hypertrophy (horizontal arrow). MV: anterior mitral leaflet


MV surgery in primary MR. In those with normal exercise stress test delay in surgery does not impair outcome at one year . Measurement of MR severity and pulmonary artery pressure during exercise may also be helpful. Figure 6 shows a brief summary of role of stress echo.

CRITERIA OF SEVERE MRCorrective surgery is indicated only in selected patients with severe chronic MR. As such it is imperative to assess if MR is severe. Echocardiography has emerged as one of the leading non-invasive diagnostic technique in cardiology and provides diagnostic and decision making algorithms in a large number of cardiac disorders including valvular regurgitation. As such echo Doppler is an

important modality to assess the severity. The role of echocardiography in MR is to determine aetiology of MR, assessing mechanism of MR which should not be confused with aetiology, determining its severity, and assessing the overall impact on cardiac chambers. Irrespective of echo Doppler grading, severe chronic MR does not exist (with rare exceptions) without clear evidence of left atrial or left ventricular enlargement. If the left ventricular end-diastolic dimension (by echocardiography) is less than 60 mm, (approximately 35 mm/m2), the diagnosis of severe chronic MR should be seriously questioned. Left atrial size may refl ect the severity and duration of chronic MR and degree of LA compliance. Besides these 2-D fi ndings, few important criteria of severe MR is as follows:

Color fl ow mapping (CFM)CFM is mainly used to get a visual estimate of severity of MR. (a) Regurgitant jet area (Figure 7): Earlier methods were used (i) to assess the percentage ratio of the maximum size of jet with the area of the left atrium (LA) in the same cardiac cycle and using multiple imaging planes. MR was considered to be severe if over 40 -50% of LA was occupied by the jet (ii) a central MR jet area of more than 8.0 cm2 was considered to be severe. However, there are several fallacies in the methods as its reproducibility was poor and several hemodynamic variables affected the jet areas. The MR jet depends on the driving force, which is LV, and depends on the pressure gradient between LV and LA. As such if LV dysfunction is present or blood pressure is low or LA pressure is high, then the jet area will appear smaller. Similarly in a hypertensive patient with mild MR, the jet area will appear larger. As such it is imperative to record blood pressure in cases of MR. Similarly the color gain is important. A high color gain will accentuate the jet size and decreasing it will reduce it. The Nyquist limit setting of the equipment also controls the colour fi lter which infl uences the size of the regurgitant jet by cutting off or allowing lower velocity fl ow signals. Thus a lower Nyquist limit will artifactually increase

the jet size and vice versa. Usually the Nyquist limit is kept around 50 cm/s. Eccentric wall-impinging jets appear signifi cantly smaller than centrally directed jets of similar hemodynamic severity. Though a larger jet area usually implies larger regurgitation, sole reliance on this parameter may be misleading. Similarly an eccentrically directed jet impinging on LA appears smaller due to loss of momentum and energy (Coanda effect). (b) Vena Contracta Width: The vena contracta (VC) is the narrowest portion of the regurgitant fl ow that occurs at or immediately downstream of the regurgitant orifi ce (Figure 8, 9). It refl ects the regurgitant orifi ce area which is a good parameter of regurgitant severity. Despite some limitations of fl ow rate

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Figure 6. Shows the role of stress echo in MR. HTN – Hypertension, LV- left ventricle

Figure 7. A case of severe MR ( arrowed) occupying most of the left atrium with an area of > 20.0 cm2

Figure 8. A diagrammatic depiction of vena contract (red arrow).

Figure 9. A case of severe MR with a vena contracta width of 10.2 mm (arrowed)

Figure 10. This is a transesophageal imaging to depicting a PISA hemisphere and radius is measured from first aliasing velocity (yellow arrow)

Figure 11. Diagrammatic representation of measurement of PISA radius


it remains a good method of assessing severity of MR. The technical details are not discussed here. A width of more that 7 mm is indicative of severe MR, while a value of < 3 mm indicates mild MR. Intermediate values between 3-7 mm may need more quantitative methods. 3-D echo now allows direct measurement of vena contracta area.

(c) Proximal Isovelocity Surface Area (PISA) or Flow Convergence: The fl ow convergence method has been recommended by many for quantitation of severity of MR. It is based on the principle that when fl ow is directed towards a regurgitant or stenotic orifi ce, then it leads to fl ow acceleration forming hemispherical shells of decreasing radius and increasing velocity (Figure 10). The radius is measured from the point of fi rst colour aliasing to the vena contracta. The larger the radius, measured from the fi rst aliasing hemisphere to the regurgitant orifi ce, the larger is the MR. It involves various assumptions and calculations. Hence a simplifi ed method is that a radius (r) greater than 10 mm at a Nyquist limit

of 40 cm/sec is indicative of severe MR. (Figure 11) Another simplifi ed approach has been validated. Assuming an MR jet velocity of 5m/sec, then as per modifi ed Bernoulli equation (gradient = 4x velocity2) it gives a 100 mmHg gradient between LV and LA in systole. With a Nyquist limit of 40 cm /sec, the effective regurgitant orifi ce area is calculated as r2 / 2. This is reasonable because majority of MR jets are between 4-6 m/sec.Pulmonary vein Doppler: In severe MR, the systolic jet impinges on systolic wave of pulmonary vein causing systolic fl ow reversal in more than one vein. Systolic blunting is suggestive but not specifi c for signifi cant MR (Figure 12-14).

QUANTITATIVE METHODSThe quantitative methods are useful, but usually all of them are not employed in day to day practice as they require multiple calculations which may be a source of error and could be time consuming. These include:

ce area: which is a fundamental measure of severity. A value ≥0.40 cm2 indicates severe MR of a primary aetiology.

Regurgitant volume per beat: which provides a measure of the severity of the volume overload. A value of ≥60 ml

indicates severe MRRegurgitant fraction: provides

a ratio of the regurgitant volume to the forward stroke volume. ≥ 50% is indicative of severe MR

Role of transesophageal (TEE) & 3-D echo: TEE is usually indicated in case the transthoracic echo is inconclusive due to patient characteristics or technical factors (Figure 2). TEE is also utilised to identify the underlying mechanism of MR and for planning MV surgery or percutaneous valve procedures and provides overall a better accuracy in localising MV pathology. 3-D echo provides better evaluation of LV/RV volumes calculation, measuring EROA and possibly automated quantitation of fl ow and regurgitant volume by 3D color fl ow Doppler. Table I summarises some of the criteria of severe MR.

MANAGEMENT ISSUESMedical Treatment: No generally accepted treatment options exist in asymptomatic patients as long term studies have not suggested benefi t of after load reduction in absence of hypertension. ACE inhibitors are started only if patient is hypertensive. Atrial fi brillation requires rate control, anticoagulation and single attempt at restoration of sinus rhythm.

SURGICAL TREATMENT OF ASYMPTOMATIC SEVERE PRIMARY MITRAL REGURGITATIONTables 2 & 3, for an easy reference, show classifi cation of recommendations and level of evidence based on clinical trials. In any severe valvular regurgitation there is a general agreement for surgery if the patient is symptomatic. However, there is general disagreement regarding surgery in asymptomatic severe valvular

Table 1: Summary of some of the criteria for severe MR Criteria Severe

Jet area >8.0-10 cm sq or large central jet (>40-50% of LA areas)

Vena contracts >7mm

PISA radlus >10 mm at Nyquist 30-40 cm/sec

Pul. Vein Systolic blunting/Reversal

LV, LA Enlarged (Chronic MR)

EROA >0.4 cm sq

Regurgitant volume >60ml /beat

Regurgitant fraction >50%

Figure 12. Shows systolic (S) and diastolic wave (D) which are timed with ECG systole and diastole Ar: atrial reversal wave, onset of which is at P wave of ECG

Figure 13. A case of severe MR showing reversal of systolic wave Doppler of pulmonary vein. It coincides with ECG systole (onset of ORS complex to end of T wave)

Figure 14. A case of severe MR showing blunting of systolic wave (S). This is suggestive but not specific for severe MR but is a supportive finding. D: diastolic wave.


regurgitation. Although surgical repair is nowadays considered gold standard but depends on patient selection for suitability for repair, associated co - morbidities, experience of surgeon with an expected success rate of about 95% and expected mortality rate of < 1% as per ACC/AHA criteria. Various factors act as guide to intervention. These include LV systolic function, LV end systolic diameter (LVESD), LA volume indexed to body surface area, degree of pulmonary hypertension, development of atrial fi brillation (AF), effective regurgitation orifi ce area (EROA) etc.

In patients with asymptomatic severe MR with normal LV functions ( EF >60%)and LV-ESV less than 40 mm are usually followed and managed conservatively and reviewed by echo every 6-12 months and followed very closely for any early symptoms. But such patients , if associated with, new onset atrial fi brillation and /or resting PASP >50 mm of Hg management guidelines suggest surgical repair (class II A, evidence B ) only as mentioned earlier, if the referral centre assures > 95% likelihood of successful repair and <1% expected mortality risk. Recent data from studies on outcome of mitral valve

repair suggest early repair than periodic monitoring as it has been proven to be safe. But proponents for watchful waiting suggest improving patient selection for surgery using natriuretic peptides (BNP value of ≥105 pg/ ml is associated with 4.6 times greater risk of heart failure in asymptomatic severe primary MR), strain parameters (Global Longitudinal strain <-20%) and 3D TEE for suitability of repair because posterior leafl et prolapse has higher success of durable repair than anterior or severe bileafl et multiscallop disease.

However, guidelines clearly indicate surgery (class I) for asymptomatic patients with severe MR and LVEF >30% and ≤60% with left ventricular end systolic diameter >40mm. Concomitant MV repair or replacement is also indicated in patients with chronic severe primary MR undergoing cardiac surgery for other indications

LA volume: In the last few years, the left atrial volume indexed to body surface area has gained signifi cance both as a guide to long-term prognosis , predictor of mortality & cardiac events and hence possibly an indication for early surgery. Tourneau et al showed that patients with

LA volume index > 60 ml/m2 had a lower fi ve year survival (53% ) as compared to 90% with LA index < 40 ml/m2. LA volume index remained a signifi cant predictor of mortality and cardiac events after adjustment by EROA

EROA : An ERO >40 mm2 has been associated with 2.9 times increased risk of total mortality, cardiac mortality 5.2 times increased risk, and cardiac events 5.7 times increased risk. Clearly, compared to expected survival, patients with an ERO >40 mm2 incur excess mortality. In patients with an ERO >40 mm2, under medical management the mortality and morbidity is considerably increased and there is excess mortality. Surgery normalises life expectancy. As such early surgery could be offered to patients based on an ERO >40 mm2.

Summary of Watchful waiting: Watchful waiting is indicated or reasonable in many patients with chronic severe MR. Such patients should undergo careful physical examination and echocardiography every 6 to 12 months or any time symptoms occur. The six month interval is preferred if stability has not been documented, there is evidence of progression, or measurements are close to the echocardiographic cut off values. A decision about watchful waiting must consider patient preference, the presence or absence of other risk factors, and whether mitral valve repair, the preferred approach which can be performed. Surgery may be offered earlier in patients with borderline values in patients in whom access to such monitoring is limited.

� Watchful waiting is recommended in asymptomatic patients with severe chronic MR who do not meet the criteria for mitral valve surgery (Grade 1B).

� Because there is variability in measurement of LVEF and end-systolic size, watchful waiting is suggested as an alternate strategy in asymptomatic patients with borderline values of LV function (LVEF 55 to 60 percent and LV end-systolic dimension 40 to 45 mm) on a single study. (Grade 2C). These patients should have repeat studies at 6 months intervals to determine

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Table 2. Classes of recommendation for management of MRClasses of Definition Suggested working to use

recommendations

Class I Evidence and/or grneral agreement Is recommended/is indicated

that a given treatment or procedure

is beneficial, useful, effective.

Class II Conflicting evidence and/or a

divergence of opinion about the

usefulness/efficacy of the given

treatment or precedure.

Class IIa Weight of evidence/opinion is in Should be considered

favour of usefulness/efficacy.

Class IIb Usefulness/efficacy is less well May be considered

established by evidence/opinion.

Class III Evidence or general agreement that Is not recommended

the given treatment or procedure

is not useful/effective, and in some

cases may be harmful.

Table 3. Levels of evidence based on clinical trialsLevel of Evidence A Data derived from multiple randomized clinical trials or meta-analyses

Level of evidence B Data derived from a single randomized clinical trial or large non-

randomised studies

Level of evidence C Consensus of opinion of the experts and/or small studies, retrospective

studies, registries


if there are consistent, reproducible changes in LV size or systolic function that would warrant intervention per the guidelines above.

� Because there is considerable variability in the accuracy of quantitation of regurgitation severity, some patients classifi ed as having moderate MR may have hemodynamically severe disease. If symptoms are present, alternate causes for symptoms should be sought. If no other cause is evident, then watchful waiting is suggested in patients with mild symptoms (NYHA functional class II ) and moderate MR who have preserved LV function (LVEF >60 percent and LV end-systolic dimension <40 mm) and no other risk factors, such as early pulmonary hypertension (Grade 2C).

OUTCOMES OF SURGICAL MITRAL REPAIRMitral valve repair has equivalent long-term outcomes to age- and gender-matched controls at >20-year follow-up. Both prospective and registry data support early repair before class 1 indications are reached as results of MV repair is superior to replacement. Prosthetic valve replacement is associated with higher operative mortality, reduced life expectancy, lifelong anticoagulation higher long-term risk of stroke and complications specifi c to valve replacement such as valve thrombosis and structural valve degeneration.

EMERGING ROLE OF PERCUTANEOUS TECHNIQUESAlthough surgery still remains as the gold standard in patients with severe primary mitral regurgitation, many patients requiring this type of treatment are

usually elderly with several comorbidities and surgery is deemed high-risk or even contraindicated in most of these cases.Recent trials using percutaneous mitral valve repair in candidates not fi t for surgery have yielded promising results. Percutaneous transcatheter mitral valve intervention is done with Mitra clip with basic principle based on Alfi eri edge to edge repair technique. The device is deployed into left atrium via transatrial approach by clipping together the free edges of valve leafl ets at the mid-portion of the leafl ets. The MV morphology suitable for Mitra-Clip, as defi ned by the Everest criteria is suffi cient leafl et tissue for mechanical coaptation, resting MV effective orifi ce area >4.0 cm2, coaptation length >2 mm, and in case of fl ail leafl et fl ail gap <10 mm, and fl ail width <15 mm. Rheumatic aetiology of MR and patients with calcifi ed leafl ets are excluded. Main drawback concluded after deployment was residual mitral regurgitation in 2/3rd of the cases although clinical follow up showed improvement in symptoms in most of the cases. Moreover, cost is also a limiting factor.

Final Caveat: Many recommenda-tions, mentioned above, may not be ap-plicable to our country because we have more of rheumatic heart disease (RHD) – and that too mixed lesion. This is in contrast to Western population, where predominant aetiology of severe MR is more of MVPS, fl ail leafl ets. MV repair is not very feasible due to technical limita-tions, but it is now gaining ground in our country. Minimally invasive percutane-ous technique for complete mitral valve repair is being performed in some centers in India now.

SUGGESTED READING1. Enriquez-Sarano M. Burden of valvular heart diseases: A

population-based study. Lancet 2006;368:1005–11.

2. Braunwald’s Heart Disease . A textbook of cardiovascular medicine 10th Ed. Chapter 63’ P1480-1487

3. Rick A Nishimura, Alec Vahanian, Mackram F Eleid, et al. Mitral valve disease—current management and future challenges- Valvular heart disease- 2 Lancet 2016;387:1324–34

4. Vahanian A, Alfieri O, Andreotti F, et al, Joint Task Force on the management of valvular heart disease , Eur Heart J 2012;33:2451–96.

5. Nishimura RA, Otto CM, Bonow RO, et al. AHA/ACC Guideline for the management of patients with valvular heart disease. Circulation 2014;129:e521–643.

6. Enriquez-Sarano M, Akins CW, Vahanian A. Mitral regurgitation. Lancet 2009;373:1382–1394.

7. Enriquez-Sarano M, Tajik AJ, Schaff HV, et al. Echocardiographic prediction of survival after surgical correction of organic mitral regurgitation. Circulation 1994;90:830–837. (10.1161/01.CIR.90.2.830

8. Tribouilloy C, Grigioni F, Avierinos JF, et al. Survival implication of left ventricular end-systolic diameter in mitral regurgitation due to flail leaflets. A long-term follow-up multicenter study. J Am Coll Cardiol 2009;54: 1961–1968.

9. Remenyi B, ElGuindy A, Smith SC Jr, et al. Valvular heart disease - 3. Valvular aspects of rheumatic heart disease. Lancet 2016;387:1335–46.

10. Shiv K. Choudhary, Sachin Talwar,Bharat Dubey, et al. Mitral valve repair in a predominantly rheumatic population: Long-term results. Tex Heart Inst J 2001;28:8-15.

11. Kang DH, Park SJ, Sun BJ, et al . Early surgery versus conventional treatment for asymptomatic severe mitral regurgitation. J Am Coll Cardiol 2014 ; 63: 2398–2407.

12. Suri RM, Vanoverschelde JL, Grigioni F, et al . Association between early surgical intervention vs watchful waiting and outcomes for mitral regurgitation due to flail mitral valve leaflets. JAMA 2013, 310 609–616.

13. Le Tourneau T, Messika-Zeitoun D, Russo A, et al . Impact of left atrial volume on clinical outcome in organic mitral regurgitation. J Am Coll Cardiol 2010,56: 570–578.

14. Messika-Zeitoun D, Johnson BD, Nkomo V, Avierinos et al 2006. Cardiopulmonary exercise testing determination of functional capacity in mitral regurgitation: physiologic and outcome implications. J Am Coll Cardiol 2006; 47:2521–2427.

15. Supino PG, Borer JS, Schuleri K, et al . 2007. Prognostic value of exercise tolerance testing in asymptomatic chronic nonischemic mitral regurgitation. Am J Card 2007;100:1274–1281.

16. Naji 16. Griffin BP, Asfahan F, Barr T, et al. Predictors of long-term outcomes in patients with significant myxomatous mitral regurgitation undergoing exercise echocardiography. Circulation 2014;129:1310–1319.

17. Zoghbi, William A Adams, David,. Bonow, Robert O et al, Recommendations for noninvasive evaluation of native valvular regurgitation.: ASE Guidelines and Standards. J Am Soc Echocardiogr. April, 2017

18. Ramdas Pai : Malignant natural history of asymptomatic aortic stenosis : Benefit of aortic valve replacement . Ann Thoracic Surg 2006;82:2116


Take Home Messages from a Meeting on “Innovations in Thrombosis Management”Held on January 7-8, 2017 at Mumbai organized by Academy of Cardiology (AOC 2017), www.acadcard.com

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SATYAVAN SHARMA, NIKHIL RAUT Keywords � thrombosis management � stent thrombosis � multi-modality imaging � prosthetic valve thrombosis

Dr. Satyavan Sharma is Professor and Head of Cardiology and Interventional Cardiologist and Dr. Nikhil Raut is Senior Registrar, Department of Cardiology, Bombay Hospital Institute of Medical Sciences, Mumbai, India

The international faculty for the meeting included Dr Charanjeet S. Rihal, Rochester, Minnesota, USA and Dr Gina Larocca from Mount Sinai, New York, USA addressed the role of multi-modality imaging in diagnosis, novel oral anticoagulants and left atrial appendage closure devices. A galaxy of national speakers enlightened on different subjects to enhance our knowledge and improve patient care.

The theme of the meeting was “Innovations in Thrombosis Management” and covered various aspects beginning from Basics in Thrombosis, Clinical Dilemmas, How to manage Stent Thrombosis?, Debates in Thrombus Therapeutics, Current scenario in Interventions, Advances in Pharmacotherapy, How to approach? (case-based) and a number of Guest lectures.The take home messages are summarised as follows:

1) SESSION 1- “BASICS IN THROMBOSIS”A. How to investigate hyper-coagulable state? (Dr M B Agarwal)a) Every patient with venous thrombo-

embolism (VTE) presenting either with deep vein thrombosis (DVT) or pulmonary embolism (PE) should be thoroughly investigated.

b) There is always an underlying cause for VTE and identifi cation is key to proper treatment. Thrombophilia profi le and screening for occult malignancy should be an integral part of investigative work-up.

c) It is also important to realize that there can be an underlying hematological abnormality (protein C, S, antithrombin III defi ciency) in a patient who is bed ridden due to a prolonged illness.

d) Another evolving area of research is that risk factors for arterial thrombosis may also contribute to venous thrombosis and there may be a role of aspirin in VTE management.


B. Risk factors for arterial thrombosis (Dr Hetan Shah)a) Every patient should be investigated

for conventional risk factorsb) Thrombophilia, polycythemia work-

up and investigations for emerging and rare risk factors should be individualized

C. Lab tests for P2Y-12 inhibitors and novel oral anticoagulant (NOAC) (Dr Uday Jadhav)a) The lab tests for P2Y-12 inhibitors

(Clopidogrel, Prasugrel, or Ticagrelor) are needed to see the effi cacy of platelet inhibition. The most popular test is Verify Now P2Y-12 system (Accumetrics) to see platelet inhibition. These tests are not recommended for day to day clinical practise but are used in some institutions prior to coronary artery bypass surgery or prior to non-cardiac surgery.

b) The NOAC (Dabigatran, Rivaroxaban, Apixaban, Edoxaban) are increasingly used and the need to check anticoagulant effect arises when patient presents with bleeding or needs a surgery.

c) The available laboratory tests include prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (APTT), thrombin time (TT) and anti- Xa assay.

d) PT and INR have a non-linear drug response and not useful. APTT values over three times usually correlates with bleeding in patients on dabigatran. Anti- Xa inhibition assays are specifi c, but expensive and at present not widely available.

2) SESSION 2: “CLINICAL DILEMMAS?”A. How to approach a patient with AF on NOAC needs a non-cardiac surgery? (Dr Amit Vora)a) Categorise the bleeding risk and risk

of vascular events while stopping NOAC.

b) If procedures are low bleeding risk, continue the drug.

c) NOAC should be discontinued 24-48 hours before if bleeding risk is

moderate and 5 days prior if bleeding risk is severe.

d) Bridging with low molecular weight heparin is not recommended.

e) Time to restart will depend on various factors. Once NOAC is re-statrted, maximum anticoagulation is obtained within 2 hours.

B) How to treat a patient on Coumadin who presents with ACS? (Dr Ajit Desai)a) Challenges in these patients include

choice of antiplatelet, thrombolysis and access site for coronary angiography. Immediately check the INR and avoid thrombolysis.

b) Do not interrupt anticoagulation and avoid bridging with heparin if INR is 2 or below.

c) Radial access is the technique of choice. Newer generation DES or BMS can be used.

d) Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel is preferable. Triple therapy (Coumadin + DAPT) should be used for a short period.

e) Bivalirudin can be used as an anticoagulant during PCI instead of heparin + IIb/ IIIa inhibitor.

C) How to deal with bleeding in a patient with mitral valve prosthesis on Coumadin? (Dr Akshay Mehta)a) Stop Coumadin. Assess the clinical

picture, degree of bleeding, Hb, INR and other necessary tests.

b) The reversal of anticoagulation is needed if there is uncontrollable, severe or intra-cranial bleeding.

c) Use of fresh frozen plasma (FFP) or prothrombin complex concentrate is recommended.

d) Cautious use of low dose vitamin k (oral or IV) is recommended.

e) The need to restart anticoagulation and bridge therapy with heparin should be decided depending on clinical picture.

D) IVC fi lters for whom? (Dr Bhavesh Vajifdar)a) Filters can be permanent or temporary

(retrievable).b) The main indication is in patients with

proximal DVT and contraindication for anticoagulation. There are several other controversial indications.

c) Filter insertion is quite safe but there can be long term complications including increased risk of subsequent DVT and IVC thrombosis.

d) Anticoagulation use is required with fi lters in selected clinical scenarios.

3) SESSION 3: “NOVEL ORAL ANTICOAGULANTS (NOAC)”- GUEST LECTURE BY DR CHARANJEET S. RIHAL, USA.a) All NOAC are not similar. The ease

of administration (once or twice a day), clinical characteristics and availability of antidote can be factors in agent selection.

b) All agents are equally effective in reducing the incidence of intracranial bleeding as compared to warfarin.

c) In patients with prosthetic valves and chronic kidney disease (CKD), vitamin k antagonists are preferred. European society of cardiology (ESC) allows use of NOAC in selected cases of tissue valves. American college of cardiology does not endorse it.

d) GI bleeding is maximum with dabigatran and least with edoxaban

e) At present, antidote is available only for dabigatran.

4) SESSION 4: “HOW TO MANAGE STENT THROMBOSIS?”A. Biovascular scaff old (BVS) (Dr D B Pahlajani)a) There have been valid concerns

regarding increased incidence of BVS thrombosis particularly from Ghost registry and Absorb II.

b) To avoid and minimize the incidence of BVS thrombosis meticulous attention to procedural details (lesion preparation, post dilatation, imaging choice), indications and antiplatelet therapy are needed.

c) Newer design BVS are being developed to address this problems.

B. DES thrombosis (Dr Anand Rao)a) The incidence of DES thrombosis

has markedly reduced in current generation DES with thinner struts.


b) Clinical characteristics, angiographic fi ndings and procedural variables determine the incidence.

C. Role of Imaging: (Dr Kirti Punamiya)a) The value of optical coherence

tomography (OCT) and intravascular ultrasound (IVUS) in understanding the mechanism of stent thrombosis (ST) was emphasized by case presentations.

b) Early ST is invariably related to procedure factors (e.g: under expansion, improper sizing, uncovered dissection).

c) Late and very late ST is mostly due to neo-atherosclerosis or DAPT interruption.

5) SESSION 5: “MULTI-MODALITY IMAGING IN INTRACARDIAC THROMBI”- GUEST LECTURE BY DR GINA LA ROCCA, USAa) Echocardiographic modalities (TTE,

TE, tissue Doppler, contrast, speckle tracking) are extremely useful, widely available but lack ability to delineate tissue characteristics. Myocardial contrast echo can be extremely useful.

b) Computed tomography (CT) imaging is extremely useful but radiation is an issue if repeated images are required.

c) High quality magnetic resonance imaging (MRI) images on advanced equipments can provide amazing information in tissue characterization.

d) Dr La Rocca showed high resolution MRI images of several diffi cult cases where a rare diagnosis can be accomplished.

6) SESSION 6: “LEFT ATRIAL APPENDAGE (LAA) OCCLUSION”- GUEST LECTURE BY DR CHARANJEET S RIHAL, USAa) Several techniques (occlusion

devices, percutaneous ligation and clip) are developing for LAA occlusion.

b) TEE and CT imaging play a crucial role in procedure planning.

c) At present maximum data is with ‘Watchman’ devices which have been

FDA approved.d) The main indication for this

specialized intervention is for patients with a high stroke risk and contraindication to long term anticoagulation.

7) SESSION 7: “DEBATES IN THROMBUS THERAPEUTICS”Debate 1: “Anticoagulation in valvar AF without prosthetic valves” (For NOAC: Dr Robin Pinto; for Vitamin k antagonist: Dr Amit Vora)The messages from the lively debate were:a) First important argument was the

defi nition of “valvar AF”. The defi nition is inconsistent in the literature. It is important to understand that when valve disease causes AF, it should be termed as valvar AF. In trials of NOAC in AF patients with valve abnormalities (mitral or aortic regurgitation, aortic stenosis, tricuspid stenosis or regurgitation of variable severity) have been included. There is a controversy whether these patients can be termed as valvar AF.

b) NOAC should not be used in patients with prosthetic valves, signifi cant mitral stenosis. There is no data to support their use in signifi cant rheumatic mitral regurgitation.

c) ESC guidelines support the use of NOAC in tissue valves but the ACC does not endorse them.

d) Vitamin K antagonists are time tested, less expensive and their use can be made safe by proper INR monitoring. Home monitoring equipments are now available.

e) Despite lack of strong data, NOAC are in use in mild to moderate valve abnormalities.

Debate 2: “Sub-massive Pulmonary Embolism” (Thrombolyse: Dr Uday Jadhav; Anticoagulation is enough: Dr Bhavesh Vajifdar)The conclusions from the heated debate were:a) Risk stratify the patient by clinical

picture, evidence of Myocyte necrosis (Trop T, MB-CPK), hemodynamic

stress (NT-pro BNP) and 2 D echocardiography

b) Thrombolysis should be considered in patients with high risk features like troponin elevation and right ventricular dysfunction on clinical or echocardiography assessment.

c) Heparin anticoagulation is suffi cient in patients not displaying high risk features.

8) SESSION 8: “CURRENT SCENARIO IN INTERVENTION”A) Thrombus aspiration in ST elevation

myocardial infarction (STEMI) and non ST elevation myocardial infarction (NSTEMI) (DR Rajiv Bhagwat)

a) Data from TASTE and TOTAL trials does not support the routine use of thrombus aspiration before primary PCI (ACC 2015 focused update have downgraded the class of recommendation to III, No benefi t).

b) Dr Bhagwat strongly justifi ed utility of thrombus aspiration in selected patients for bail out (ACC- II b, C) by showing case scenarios of patients with large thrombus burden.

B) Immediate versus deferred stenting in STEMI (Dr Anil Potdar)a) The current practice of immediate

stenting is justifi ed in majority of the cases.

b) Data from DEFER STEMI trial have advocated use of deferred stenting in primary PCI in high risk STEMI patients to prevent no refl ow and to increase myocardial salvage

9) SESSION 9: “ADVANCES IN PHARMACOTHERAPY”A) Future of anti-thrombotics in ACS (Dr Anand Rao)a) Antiplatelet agents: Use of

clopidogrel will decline for PCI in ACS. Ticagrelor, prasugrel and IV Cangrelor will be the front runners. Glycoprotein IIb/ IIIa inhibitors will be used only in limited circumstances.

b) Anticoagulants: Low molecular weight heparin (LMWH) and unfractionated heparin will continue to be used. Bivalirudin may be

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preferred in situations where there is high bleeding risk.

c) Vorapaxar is an orally active selective inhibitor of thrombin receptor PAR-1. This drug has been approved by FDA in reducing ischemic events in patient with a history of myocardial infarction (MI). The benefi t of vorapaxar in addition to aspirin and clopidogrel is modest and must be weighed against the increase in bleeding events.

d) There is a data emerging with rivaroxaban and edoxaban in addition to dual antiplatelet for reducing ischemic events.

B) Newer oral anticoagulants in VTE (Dr S B Gupta)a) NOACs have potential to replace

warfarin for majority of patients with VTE

b) In acute symptomatic VTE, NOACs are non-inferior to conventional anticoagulation treatment with less bleeding.

c) NOAC have been extensively evaluated for thromboprophylaxis in medical and surgical patients.

C) Antidotes to NOAC (Dr Milind Phadke)a) The specifi c antidotes to NOAC are

developing, very expensive and not available in our country

b) The bleeding should be categorized as mild, moderate or severe. If the bleeding is mild, discontinuation of the agent and local measures are enough.

c) If the bleeding is moderate, supportive measures (volume expansion), RBC or platelet transfusion are needed.

d) For life threatening bleeding, haemodialysis may be needed. Fresh frozen plasma is very effective. Idarucizumab (Praxbind) is commercially available as a specifi c antidote to dabigatran.

10) SESSION 10: “HOW DO I APPROACH?”A) LV thrombus in STEMI, dilated cardiomyopathy (Dr Akshay Mehta)a) LV thrombus can occur within 24

hours of STEMI. New thrombus can occur after discharge in patients with dyskinesia or ventricular aneurysm.

b) Trans-esophageal echocardiography (TEE), apical wall motion score and myocardial contrast echo are extremely useful in diagnosis.

c) Anticoagulation with warfarin (ACC Class IIa, C recommendation) with DAPT is needed. Triple therapy should be given for brief period and INR of 2 should be aimed. Aspirin dose can be lowered to 75mg daily.

d) There are scattered reports with NOAC.

B) LA thrombus in patient evaluated for BMV (Dr Milind Phadke)a) TEE is crucial for delineation of

clot and defi ning the details. A classifi cation is available to categorize the clot and choose selected patients in whom BMV (balloon mitral valvotomy) is feasible.

b) An experienced interventional cardiologist can safely perform BMV in selected cases of LA clot with meticulous attention to trans-septal puncture and other technical details.

C) Right Heart Thrombi: (Dr Robin Pinto)a) Right heart thrombi are rare. The

mobile thrombi are associated with increased mortality in patients with pulmonary emboli.

b) Right atrium (RA) should be screened routinely in patients with AF to diagnose RA thrombi.

c) TEE is extremely useful, whereas CT and MRI help in differentiation with other mass lesions.

D) Thrombus on Central Venous Catheters (CVC) (Dr Satyavan Sharma)a) CVC related thrombosis can occur in

patients undergoing dialysis, therapy for cancer, etc.

b) Thrombotic complication can occur in any vein- subclavian, internal jugular or femoral.

c) Loss of catheter function, pulmonary embolism are presenting features.

Diagnosis can be made by ultrasonography, echocardiography, CT, MRI or venography.

d) Therapy includes removal of catheter, anticoagulation, thrombolysis or surgical intervention.

11) SESSION 11: “HOW TO MANAGE AND PREVENT PROSTHETIC VALVE THROMBOSIS (PVT)?”- GUEST LECTURE BY DR O. P. YADAVAa) The fi rst important question to

answer is whether prosthetic valve is obstructed or not? Clinical examination, fl uoroscopy, TTE (if feasible TEE) and Doppler interrogation provide useful information.

b) For majority of patients with thrombotic obstruction of mitral or aortic prosthesis, re-operation is the best choice.

c) There is increasing role of lower dose, sustained infusion of tissue plasminogen activator (tpa) thrombolysis in selected cases.

d) Optimal anticoagulation, addition of aspirin (specially in mitral valve prosthesis) and meticulous attention to surgical techniques are crucial in prevention of PVT.

Session 12: “Innovations in interventional therapies for structural heart disease”- Guest lecture by Dr Charanjeet S. Rihal, USAa) Percutaneous interventions play an

increasingly role in structural heart disease. Advanced imaging (TEE, 3D and CT, fl uoroscopy) and meticulous application to procedural planning remain key to success

b) Transcatheter aortic valve replacement (TAVR) is a new and transformational technology in patients with severe aortic valve stenosis (AVS). The safety and effi cacy in high risk patients have been proved by short and long term data. The technique is now utilized in selected intermediate risk patients and it is likely that in future this will be applied to low risk groups. Several new valve designs are being


developed and the procedure can be done from various routes.

c) Paravalvar leak (PVL) is a common problem after prosthetic valve surgery. Various types of vascular plugs and devices have been successfully used for aortic and mitral PVL.

d) Mitraclip is a transcatheter mitral valve repair procedure which has proved effective and safe in selected patients in degenerative mitral regurgitation (MR) at high risk for surgery. The technique also has a role in severe secondary MR. Several other devices are being developed for percutaneous repair or replacement.

e) Coronary arterial fi stulas and several other rare structural malformations can be treated percutaneously by experienced interventional cardiologists.

12) SESSION 13: “ROLE OF MULTI-MODALITY IMAGING IN DIAGNOSIS OF LEFT ATRIAL APPENDAGE (LAA) THROMBUS (WITH DIAGNOSIS,

PROGNOSIS, TREATMENT AND NEW OPTIONS)”- GUEST LECTURE BY DR GINA LAROCCA, USAa) LAA thrombus is a common problem

and can occur even in patients with intermittent atrial fi brillation

b) Assessment of LAA velocities by Doppler and morphology by TEE, cardiac CT or MRI provide crucial information. Chicken wing type of LAA is seen in 50% and less common caulifl ower variety is frequently associated with thrombi.

c) Anticoagulation by NOAC is an attractive treatment option. LA occlusion devices, percutaneous plication and surgical ligation are options in selected cases.

13) SESSION 14: “ADVANCES IN THE MANAGEMENT OF ACUTE ISCHEMIC STROKE (AIS)”- GUEST LECTURE BY DR RAKESH SINGHa) AIS is amenable to early intervention.

Till date, there has been lack of awareness on part of medical

profession and public in recognizing AIS as potentially treatable emergency. Improved education together with better organization (stroke units) may improve recovery from this potentially devastating condition.

b) Intravenous tpa is of proven benefi t for selected patients with acute ischemia. Thrombolysis should be delivered in speciality hospital setting after prompt imaging.

c) Patients with occlusions of large intracranial arteries may also undergo intervention with intra-arterially deployed devices.

d) The risk of life threatening intra-cranial hemorrhage exists.

e) The management of AIS is moving in the direction of STEMI treatment although slowly and with major differences in antithrombotic regimens and preservation of brain tissue.

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Biventricular Hypertrophic Obstructive Cardiomyopathy in a Neonate

IMAGE

SR MITTAL

Keywords � bilateral hypertrophic obstructive

cardiomyopathy � pulmonary artery hypertension � asymmetrical septal hypertrophy � chromosomal disorders

Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

BIVENTRICULAR HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY IN A NEONATEHypertrophic cardiomyopathy is rarely reported in neonates.1-4 Concomitant right ventricular involvement is reported only in two cases.1,4 We report a case of biventricular hypertrophic cardiomyopa-thy with mild biventricular outfl ow tract obstruction in a neonate.

CASE REPORTA 2 days old neonate was referred for echocardiography. ECG showed right axis deviation and clockwise rotation. Visceral situs was normal. Systemic and pulmo-nary veins drained normally. Atrio-ven-tricular and ventriculo-arterial relations

were normal. All valves were structurally normal. Th ere was no shunt. Interven-tricular septum (IVS) measured 6.6 mm in end diastole(Figure 1, D1). Left ven-tricular posterior wall (LVPW) thickness was 3.3 mm in end diastole (Figure 1, D3). Right ventricular anterior wall (RVAW) measured 6.3 mm in end diastole (Figure 1, D2). Th ere was diastolic as well as sys-tolic fl attening of interventricular septum (Figure 2). Right ventricular papillary muscle was hypertrophied (Figure 3 a & b). Th ere was mild gradient across right ventricular outfl ow tract (RVOT) (Fig-ure 4) and left ventricular outfl ow tract (LVOT) (Figure 5). Pulmonary artery peak velocity was 0.95m/s with an ac-celeration time of 89 ms. Th ere was mild

AbstractBiventricular hypertrophic obstructive cardiomyopathy is rarely reported in neonates. We report a case of biventricular hypertrophic cardiomyopathy with mild biventricular outfl ow tract gradient and moderate pulmonary artery hypertension in a neonate of 2days. Intraventricular septal thickness was 6.6 mm and right ventricular anterior wall measured 6.3 mm. Right ventricular papillary muscle was also hypertrophied. There was diastolic as well as systolic fl attening of interventricular septum. Right ventricular systolic pressure was 32.2 mm Hg as calculated from mild Tricuspid regurgitation (TR) jet. Tissue Doppler imaging of lateral tricuspid annulus revealed a’>e’. Part of PAH and RV hypertrophy could be secondary to incomplete regression of circulatory changes of intrauterine life. Maternal diabetes and chromosomal disorders are common causes. Beta blockers are the treatment of choice.


TR (Figure 6 a). Right ventricular systolic pressure as calculated from TR jet was 32.2 mm Hg (Figure 6b). Interatrial sep-tum (IAS) was deviated to left (Figure 7). Inferior vena cava (IVC) was normal with normal inspiratory collapse (Figure 8). Hepatic vein fl ow was normal (Figure 9). Doppler evaluation of tricuspid fl ow (Fig-ure 10) showed alternating prominence of A wave suggesting impaired relaxation of right ventricle. Tissue Doppler imaging of lateral mitral annulus (LMA) (Figure 11a) revealed a’>e’. Tissue Doppler imaging of medial mitral annulus (MMA) (Figure 11b) showed a normal pattern. Tissue Doppler imaging of medial tricuspid an-nulus (MTA) was normal (Figure 12 a) where as lateral tricuspid annulus(LTA)

(Figure 12b) revealed a’>e’.

DISCUSSIONIVS thickness of 6.6 mm and LVPW thickness of 3.3 mm was suggestive of asymmetrical septal hypertrophy of left ventricle (HCM). RVAW thickness of 6.3 mm and hypertrophy of right ventricular papillary muscle were suggestive of RV HCM. PA fl ow acceleration time of 89ms, RVSP 32.2 mm Hg and systolic and dias-tolic fl attening of IVS were suggestive of raised RV pressure. a’>e’ on tissue Dop-pler evaluation of lateral mitral and lat-eral tricuspid annuli were suggestive of diminished compliance of LV and RV respectively.

As the neonate was only 2 days old, it is possible that pulmonary artery hy-pertension (PAH) and right ventricular hypertrophy were due to incomplete re-gression of circulatory changes of intrau-terine life. LVHCM can also contribute to PAH.5 However, hypertrophy of IVS and RV papillary muscle support diagno-sis of HCM. IVS thickness of >4.5 mm is considered suggestive of foetalHCM6. In infants, IVS thickness of > 6mm is consid-ered abnormal.7

Foetal HCM is reported in diabetic mothers.6 It is attributed to increased in-sulin like growth factor 1 in neonates.8

Figure 1. M-mode echocardiogram from parasternal long axis view showing thickened IVS(D1) and thickened right ventricular anterior wall (AW) (D2) with normal thickness of LV posterior wall (PW) (D3).

Figure 2. Parasternal short axis view in diastole(ED) and systole (ES) showing thickened interventricular septum (IVS) and right ventricular (RV) anterior wall (AW). IVS is flat in diastole as well as systole. RV papillary muscle is thickened (arrow). LV- Left ventricle.

Figure 3a. Subcostal short axis view showing thickened right ventricular (RV) papillary muscle (arrow). Ao- Aorta, RA- Right atrium, RVOT- Right ventricular outflow tract, TV- Tricuspid valve. b. Parasternal RV inflow view showing thickened papillary muscle (arrow). RA- Right atrium, RVOT- Right ventricular outflow tract, Ao—Aorta.

Figure 4. Pulsed Doppler evaluation across right ventricular outflow tract (RVOT) showing mild gradient across RVOT. RV- Right ventricle, PA- Main pulmonary artery.

Figure 5. Pulsed Doppler evaluation across left ventricular outflow tract (LVOT) showing gradient across LVOT. LV- Left ventricle, Ao- Aorta, RA- Right atrium, RV- Right ventricle.

IMAGE


Such foetal HCM can regress over months. HCM in infants is usually a part of chro-mosomal disorders eg. Down syndrome,9 Noonan syndrome,10 Noonan syndrome with multiple lentigines (Leopard syn-drome),7,11 Costello syndrome.12 Other rare mutations that have been reported to

be associated with HCM include PTPN 11 Q 5 10 E mutation7, GTBPP 3 muta-tion,13 COA 62 and PRKAG 2 gene mu-tation15. Metabolic diseases e.g., Pompe’s disease15,16 and Tyrosinemia type 1 can also produce HCM in infants.17 HCM as-sociated with Tyrosinemia type 1 is also reversible with management of disease.17

HCM may progress rapidly in Noonan syndrome with multiple lentigines7 and those with PTPN 11 Q5 10 E mutation.7 Primary HCM may be associated with VSD or TOF.18 Noonan syndrome is usu-ally associated, with dysplastic pulmonary valve Myeloproliferative disorder has been reported in a neonate with Noonan syndrome and HCM.3 Down syndrome is usually associated with atrio-ventricular septal defects. Pulmonary vein stenosis has been reported with down syndrome.9 Infants with Costello syndrome can have additional pulmonary stenosis, ASD or VSD.12

Neonates with severe RVOT obstruc-tion may show mean frontal plane QRS axis in right upper quadrant, right atrial enlargement and abnormal right ventric-ular dominance.4 In such cases, skiagram of chest may reveal abnormal prominence of main pulmonary artery.4 Pulsed Dop-pler tissue imaging and cardiac MRI are useful in detecting right ventricular in-volvement in apparently left -sided dis-ease.19,20,21

Figure 6. Fig. 6 a. Colour Doppler evaluation in apical four chamber view showing mild tricuspid regurgitation(TR). LV- left ventricle, LA- Left atrium, RV- right ventricle, RA-right atrium. b. Pulsed Doppler evaluation of TR jet showing calculated right ventricular systolic pressure of 32.2 mm Hg. RA- Right atrium, RV- Right ventricular , LV- Left ventricle.

Figure 7. Subcostal four chamber view showing leftward shift of interatrial septum (arrow) LA- Left atrium, LV- Left ventricle, RA- Right atrium, RV- Right ventricle.

Figure 8. M-mode echocardiogram of inferior vena cava (IVC) showing normal dimension and inspiratory collapse.

Figure 9. Pulsed Doppler evaluation of hepatic vein (HV) showing normal flow. S-systolic, D-Diastolic, A-atrial reversal.

Figure 10. Pulsed Doppler evaluation of tricuspid flow showing A>E in alternate beats.

Figure 11a. Doppler tissue imaging of lateral mitral annulus showing a’>e’. b. Doppler tissue imaging of medial mitral annulus showing normal pattern.


Figure 12. a. Doppler tissue imaging of medial tricuspid annulus showing normal pattern. b. Doppler tissue imaging of lateral tricuspid annulus showing a’>e’.

Cardiac catheterization can be hazardous in infants and may precipitate hypoxic crisis or cardiac arrest.8 Beta blockers are the treatment of choice.4 Treatment with rapamycin analogue has been shown to improve heart failure symptoms in an in-fant with Noonan syndrome with multiple lentigines.6 However, there was no rever-sal of cardiac hypertrophy. Alcohol septal ablation is not very eff ective in infants. Surgery is usually not rewarding and post operative period is complicated by heart failure or arrhythmias.1,4 Extracorporeal membrane oxygenation support may be helpful in severe HOCM associated with persistent pulmonary hypertension.4 It allows time for an amelioration of PAH in patients with reversible HCM. Infants with progressive obstruction and severe heart failure may need cardiac transplan-tation.6

REFERENCES1. Jivanji SG, Daubency P, Franklin R, Sheppard M. Right

ventricular cavity near obliteration in neonatal severe bi-ventricular hypertrophic cardiomyopathy. BMJ Case Rep 2014; PMID 25336549 DOI 10.1136/ber-2014-205041.

2. Baertling F, van den Brand MAM, Hertecant JL. Al- shamsi A, P van den Heuvel L, Distelmaier F, et al. Mutations in COA 6 cause cytochrome C oxidase deficiency and neo-natal hypertrophic cardiomyopathy. Hum Mutat 2015; 36:34-8.

3. Yogasaki H, Nakane T, Hasebe Y, Watanabe A, Kise H, Toda T, et al. Co-occurrence of hypertrophic cardiomyo-pathy and myeloproliferative disorder in a neonate with Noonan syndrome carrying Thr 73 tle mutation in PTPN 11. Am J Med Genet A 2015;167 A:3144-7.

4. Barr PA, Celermajer JM, Bowdler JD, Cartmill TB. Idi-opathic hypertrophic obstructive cardiomyopathy caus-ing severe right ventricular outflow tract obstruction in infancy. Br Heart J 1973; 35:1109-15.

5. Goldberg JF, Mery CM, Griffitho PS, Parekh DR, Welty SE, Bruonicki RA, et al. Extracorporeal membrane oxygena-tion support in severe hypertrophic obstructive cardiomy-opathy associated with persistent pulmonary hyperten-sion in an infant of a diabetic mother. Circulation 2014; 130:1923-5.

6. Elmekkawi SF, Mansour GM, Elsafty MSE, Hassanin AS, Laban M, Elsayed HM. Prediction of foetalhypertrophic cardiomyopathy in diabetic pregnancies compared with postnatal outcome. Clinical Medicine Insights : Women’s Health 2015: 8:39-43.

7. Hahn A, Lauriol J, Thul J, Behnke – Hall K, Logeswaran T, Schanzer A, et al. Rapidly progressive hypertrophic car-diomyopathy in an infant with Noonan syndrome with multiple lentigines. Palliative treatment with a Rapamy-cin analog. Am J Med Genet 2015; 0(4) : 744-51.

8. Gonzalez AB, Young L, Doll JA, Morgan GM, Crawford SE, Plunkett BA. Elevated neonatal insulin like growth factor 1 is associated with foetalhypertrophic cardiomyopathy in diabetic women. Am J obstet gynecol 2014; 211:290.e 1-7.

9. Mahadevaiah G, Gupta M, Ashwath R. Down syndrome with complete atrioventricular septal defect, hypertrophic cardiomyopathy and pulmonary vein stenosis. Tex Heart Inst J 2015;42:458-61.

10. Schinkel AFL, Vos J. Biventricular hypertrophic obstruc-tive cardiomyopathy in Noonan syndrome. Int J Cardiol 2007; 115: E 22- E23.

11. Carcavilla A, Santome JL, Pinto I, Sanchez- Pozo J, Na-varro EG. Martin – Frias M, et al LEOPARD syndrome: A variant of Noonan syndrome strongly associated with hypertrophic cardiomyopathy. Revista Espanola de car-diologia (English edition) 2013; 66: 350-6.

12. Guvene O, Sengul FS, Saygi M, Ergul Y, Guzeltas A. Hyper-trophic cardiomyopathy and Costello syndrome : review of recent related literature with case report. Turk Kardiyol Dern Ars 2014;42:767-70.

13. Kopajtich R, Nicholls TJ, Rorbach J, Metodiev MD, Fre-isinger P, Mandel H, et al. Mutation in GTPBP 3 cause a mitochondrial translation defect associated with hyper-trophic cardiomyopathy, lactic acidosis and encepha-lopathy. Am J Hum Genet 2014;95:708-20.

14. Kelly BP, Russell MW, Hennessy JR, Ensing GJ. Severe hypertrophic cardiomyopathy in an infant with a novel PRKAG 2 gene mutation: potential difference between infantile and adult onset presentation. Pediatr Cardiol 2009; 30:1176-9.

15. Ekici F, Cevik BS, Gunduz M. Biventricular hypertrophic cardiomyopathy in a baby diagnosed with pompe dis-ease. Turk Kardiyol Dern Ars- Arch Turk Soc Cardiol 2012; 40:558.

16. Patra S, Subramanium A, Mahimaiha J, Sastry UM, Nanjappa MC. Apical hypertrophic cardiomyopathy in an infant :first presentation of Pompe’s disease. World J Pediatr Congenit Heart Surg 2014;5:491-3.

17. Mohamed S, Kambal MA, Al Jurayyan NA, Al- Nemri A, Babiker A, Hasanato R et al. Tyrosinemia type 1 : a rare and forgotten cause of reversible hypertrophic cardio-myopathy in infancy. BMC Res Notes 2013;6:362.

18. Somerville J, Beuo L. Congenital heart disease associ-ated with hypertrophic cardiomyopathy. Br Heart J 1978; 40:1034- 9.

19. Maron MS, Hauser TH, Dubrow E, Horst TA, Kissinger KV. Udelson JE, et al. Right ventricular involvement in hyper-trophic cardiomyopathy. Am J Cardiol 2007;100:1293-8.

20. Severino S, Caso P, Cicala S, Galderisi M, De Simon L, D’ Andrea A, et al. Involvement of right ventricle in left ven-tricular hypertrophic cardiomyopathy: Analysis by pulsed Doppler tissue imaging. Eur J Echocardiography 2000; 1:281-8.

21. Morner S, Lindquist P, Waldenstrom A, Kazzam E. Right ventricular dysfunction in hypertrophic cardiomyopathy as evidenced by the myocardial performance index. Int J Cardiol 2008;124:57-63.

IMAGE


‘J’ Point

ECG OF THE MONTH

SR MITTAL

Abstract'J' point is the junction of end of depolarization (QRS) and onset of repolarization (ST segment). When J point is elevated above baseline, it is termed as early repolarization. Elevation can be in the form of slurring of terminal QRS or a distinct dome-shaped wave (J wave). When early repolarization is associated with documented polymorphic ventricular tachycardia (VT), ventricular fi brillation (VF) or aborted sudden death, it is termed as early repolarization syndrome. RBBB pattern with ST segment elevation and T wave inversion in leads V1 and V2 are termed as Brugada syndrome. It can be associated with VF and sudden cardiac death.

Keywords � Brugada syndrome � early repolarization � idiopathic VF � J wave � sudden cardiac death

‘J’ POINTJ point is the point of junction of end of depolarization (QRS) with onset of re-polarization (ST Segment). Th is is usu-ally not a sharp point because end of QRS smoothly merges in ST segment. Nor-mally J point is at the level of P-R segment smoothly (baseline). If it is elevated above the baseline, it forms a smooth dome shaped wave at the end of QRS (J wave). J wave has the same polarity as preceding QRS complex.1 J wave should be diff er-entiated from terminal notch produced due to intraventricular conduction defect. Notch due to intraventricular conduc-tion defect are relatively sharp and show tachycardia or prematurity-dependent augmentation.2 Structural heart disease is common. On the other hand J wave is smooth, dome-like and shows bradycar-dia or pause dependent augmentation.2 It is usually seen in absence of structural heart disease. At times J wave may not be distinct but may be buried inside the QRS resulting in slurring of terminal part Dr. SR Mittal is Head, Department of Cardiology at Mittal Hospital and Research Centre, Ajmer, Rajasthan

Figure 1. Electrocardiogram showing ‘J’ waves (arrows) in leads I, V1-V6 followed by rapid upsloping ST segment.


of QRS.2 Mostly J wave is a normal variant especially in vagotonic indi-viduals e.g. young athletes or hard manual workers. Normally it is most prominent in left precordial leads (V4-V6), is < 0.2 mv and is followed by rapidly upsloping ST segment (Figure 1). When variations in J wave are associated with polymorphic VT, Idiopathic VF, arrhythmic syncope or aborted sudden cardiac death, these are called “J wave syndrome”. Arrhyth-mic syncope are characterised by absence of prodromes or specifi c triggers e.g. hot, crowded surrounding, pain, sight of blood or prolonged standing.2 Arrhyth-mic syncope are more likely to have uri-nary incontinence.2Clinically important J wave syndromes include(1) Early repolarization syndrome(2) Brugada syndrome(3) Acute myocardial ischemia(4) Arrhythmogenic right ventricular

cardiomyopathy.

(1) EARLY REPOLARIZATION SYN-DROMEEarly repolarization of endocardium as compared to epicardium results in gen-esis of J wave3 (Figure 2 a, b). Th e term ‘early repolarization syndrome” is used only when the ECG fi nding is associ-ated with idiopathic VF.4 Idiopathic VF is more frequently associated with following electrocardiographic features-(a) J wave > 0.2 mv5

(b) Presence of J wave in inferior (II, III, aVF) as well as lateral (I, aVL, V4-V6) leads (Figure 3). Global (inferior, lat-eral and right precordial leads (Fig-ure 4)) presence of J wave is more frequently associated with idiopathic VF6.

(c) Horizontal or downsloping ST seg-ment7 (Figure 1,5,6).

(d) Transient increase in the amplitude of J point elevation specially during epi-sodes of myocardial ischemia.

(e) Association of prominent J wave with notching of QRS8 (Figure 7, 8).

(f) Presence of co-existing Brugada ECG pattern or short QT interval.2

Although these fi ndings are more fre-quently associated with idiopathic VF, etiological relation is not proved.9 Fur-

ther, patients with above-mentioned fea-tures alone need not necessarily have a risk of VF. Electrophysiological study is not justifi ed in asymptomatic patients. Similarly implantable cardiovertor-de-fi brillator is not to be considered unless there is documented VF or patient is a survivor of sudden cardiac death. Vagoto-nia (e.g., during sleep) increases chances of early repolarization associated VF.10 Sympathetic stimulation suppresses early repolarization and associated arrhythmi-as.10 Quinidine is eff ective in suppressing arrhythmias in early repolarization syn-

(b)(a)

ECG OF THE MONTH

Figure 2. Diagramatic representation of genesis of J wave (a) Normal action potentials from epicardium and endocardium with normal QRS (b) Early repolarization of endocardium producing ‘J’ wave (J) -Epicardium, ----Endocardium.

Figure 3. Electrocardiogram showing ‘J’ waves (arrows) in leads II, III, aVF with horizontal ST segment.

Figure 4. Electrocardiogram showing ‘J’ wave (arrow) in lead V2.

Figure 5. Diagramatic representation of various types of ST segment following a ‘J’ wave (a) rapidly upsloping (b) horizontal (c) downsloping.

Figure 6. Electrocardiogram showing early repolarization with upsloping ST segment (arrows) in leads II, III, aVF. There is slurring of terminal QRS in leads III and aVF.

Figure 7. Electrocardiogram showing fragmented QRS (arrows) with early repolarization.


drome.2 Beta blockers, verapamil, mexile-tine, Amiodarone and class Ic agents are not eff ective. An idiopathic VF should be considered to be associated with early repolarization only aft er excluding other etiologies by detailed evaluation. Other causes of VF without structural heart dis-ease also need to be excluded. Th ese in-clude long QT-syndrome, short QT syn-drome, catecholaminergic arrhythmias and Brugada syndrome.

(2) BRUGADA SYNDROME It is produced by delayed depolarization over anterior aspect of the Th e right ven-tricular outfl ow tract (RVOT) epicardi-um.2 Classical electrocardiographic fi nd-ings (Type I) include right bundle branch

block pattern with ST-segment elevation of >2 mm and inverted T waves in right precordial leads V1,V2

11(Figure 9a). Sensi-tivity is increased by recording these leads in 2nd and 3rd intercostal spaces.2 Saddle back types T segment elevation of more than 2 mm with a positive or biphasic T wave has been termed as type 2 (Figure 9b). Saddleback ST-segment elevation of less than 2 mm with positive T wave is termed type 3 (Figure 9c). Type 2 and 3 are not classical and do not carry same signifi cance as type I. However, in a given patient all three patterns may be recorded at diff erent times. Type 1 pattern may be transient and appear spontaneously or aft er administration of sodium channel blockers e.g., Procainamide, Flecainide, Azmalin or Pilsicainide.12 Hypokalemia and oral steroid may also act as proar-rhythmic triggers in Brugada and early repolarization syndrome.13 Fever can also unmask ECG signs of Brugada syn-drome. Several other drugs can produce Brugada-like ECG pattern. Th ese include phenothiazines, tricyclic antidepressants, calcium channel blockers (verapamil, diltiazem), beta blockers (Propranolol, Nadolol).2 Clinical signifi cance of such an ECG change is not clear. In contrast, Qui-nidine cilostazol, isoproterenol and orci-prenaline normalise the ECG and help in controlling arrhythmias. Amiodarone is ineff ective.2 As the classical pattern may appear only transiently, Holter monitor-ing may be required to detect classical fi ndings in patients with strong clini-

cal suspicion.12 Brugada-like ECG can also occur in right bundle branch block (RBBB), pectus excavatum, arrhythmo-genic right ventricular cardiomyopathy, occlusion of left anterior descending ar-tery or conus branch of right coronary artery which supplies the RVOT. Right bundle branch block pattern of Brugada syndrome may not be accompanied by S wave in the left precordial leads. It sug-gests that R’ in right precordial leads is an accentuation of J wave. It can be an asymptomatic ECG fi nding. Term’ “Bru-gada syndrome” should be used only when such electrocardiographic fi nding is associated with (a) Arrhythmogenic syncope or aborted

sudden death or (b) Documented polymorphic VT or idi-

opathic VF(c) Family history of sudden cardiac

death in young (less than 45 years) or (d) Presence of classical ECG fi ndings in

other family membersInducibility of VT or VF during electro-physiological study is important only in presence of clinical fi ndings. Presence of QRS fragmentation correlates with worse prognosis.14 Other electrocardiographic markers for greater risk of arrhythmias include(a) Coexistence of type 1 Brugada pat-

tern with early repolarization in infe-rolateral leads.2

(b) Dynamic changes in the prominence of J wave and ST-segment elevation and confi guration.15

(c) Wide (> 40 ms) and / or large S wave in lead I. It is thought to be due to signifi cant delay in anterolateral right ventricular outfl ow tract.16

(3) Other conditions where the J wave can be prominent2

(a) Acute myocardial ischemia(b) Acidosis(c) Hyperkalemia(d) Hypercalcemia17

(e) Arrhythmogenic right ventricular cardiomyopathy

(f) Hypoxia (g) Hypothermia

REFERENCES1. Mirvis DM, Goldberger AL. Electrocardiography. In Mann

DL, Zipes D P, Libby P, Bonow RO(eds). Braunwald’s Heart Disease. Elsevier, Philadelphia ; 2015: 44-152.

Figure 8. Diagramatic representation of electrocardiographic features of early repolarization syndrome likely to be associated with idiopathic ventricular fibrillation. N- notch in QRS, J- prominent ‘J’ wave and downsloping ST segment.

Figure 9. Electrocardiographic types of Brugada syndrome (a) Type 1 (b) Type 2 (c) Type 3.


ECG OF THE MONTH

2. Antzelevitch C, Yan GX, Ackerman MJ, Borggrefe M, Cor-rado D, Guo J, et al. J wave syndrome expert consen-sus conference report: Emerging concepts and gaps in knowledge. Heart Rhythm 2016; 13: e296- e324.

3. Sethi KK, Sethi K. Chutani SK. Early repolarization and J wave syndromes. Indian Heart J 2014; 66:443-52.

4. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inher-ited primary arrhythmia syndromes. Europace 2013;15: 1389-406.

5. Haissaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016-23.

6. Antzelevitch C, Yan JX. J wave syndromes – contempo-rary review. Heart Rhythm 2010;7:549-58.

7. Rosso R, Glikson E, Belhassen B, Katz A, Halkin A, Steinvil A, et al. Distinguishing “benign” from “malignant early repolarization “ ‘ the value of ST segment morphology. Heart Rhythm 2012;9:225-9.

8. Merchant FM, Noseworthy PA, Weiner RB, Singh SM, Ruskin JN, Reddy VY. Ability of terminal QRS notching to distinguish benign from malignant electrocardiographic forms of early repolarization. Am J Cardiol 2009;104: 1402-6.

9. Olgin JE, Zipes DP. Specific arrhythmias : Diagnosis and treatment. In Mann DL, Zipes DP, Libby P, Bonow RO(eds). Braunwald’s Heart Disease. Elsevier, Philadelphia; 2015: 748-97.

10. Satish OS, Srivastav KS. Early repolarization changes in ECG: Are they benign or malignant? J Assoc Physicians India 2016; 64 : 51-4.

11. Brugada P, Brugada J. Right bundle branch block, per-sistent ST segment elevation and sudden cardiac death: a distinct clinical and electrocardiographic syndrome: a multicenter report. J Am Coll Cardiol 1992; 20:1391-6.

12. Priori SG, Napolitano C. Genetics of channelopathies and clinical implications. In Fuster V, Walsh RA, Harrington RA (eds) Hurst’s The Heart. Mc Graw Hill, New York; 2011: 897-910.

13. Talib AK, Sato N, Myojo T, Sugiyama E, Nakagawa N, Sakamato N, et al. Insight into specific pro-arrhythmic triggers in Brugada and early repolarization syndromes: results of long-term follow up. Heart Vessels 2016; doi10.1007/s00380-016-0828-8.

14. Morita H, Kusano KF, Miura D, et al. Fragmented QRS as a marker of conduction abnormality and a predictor of prognosis of Brugada syndrome. Circulation 2008; 118: 1697-704.

15. Postema PG, Wilde AA. Do J waves constitute a syn-drome? J Electrocardiol 2013; 46: 461-5.

16. Calo L, Giustetto C, Martino A, Sciarra L, Cerrato N, Mar-ziali M, et al. A new electrocardiographic marker of sud-den death in Brugada syndrome. The S wave in lead I. J Am Coll Cardiol 2016; 67: 1427-40.

17. Sonoda K, Watanabe H, Hisamatsu T, Ashihara T, Ohno S, Hayashi H, et al. High frequency of early repolarization and Brugada – type electrocardiograms in hypercalce-mia. Ann Noninvasive Electrocardiol 2016; 21:30-40.

Q1. Normally J point is (A) Isoelectric(B) Elevated(C) Depressed (D) Dome-shaped

Q2. Polarity of J wave is (A) Isoelectric (B) Same as preceding QRS(C) Opposite to preceding QRS(D) Some as following ST-segment

Q3. J wave is produced by early repo-larization of

(A) Epicardium (B) Endocardium (C) ‘M’- layer(D) All layers

Q4. J wave is a normal variant (A) In athletes(B) In hard manual workers (C) In anxiety(D) Aft er exercise

Q5. “Early repolarization syndrome” is diagnosed by

(A) ECG (B) Clinical profi le(C) ECG + clinical profi le (D) Electrophysiological study

Q6. Which ECG fi ndings of “early repolarization syndrome” are

MCQsrecurrent VF in a case of early repolarization syndrome-

(A) Quinidine(B) Procainamide (C) Isoproterenol (D) Amiodarone

Q11. Brugada syndrome is caused by delayed depolarization over

(A) Anterior aspect of RVOT epicar-dium

(B) LVOT epicardium (C) Apex of RV(D) Interventricular septum

Q12. In classical Brugada syndrome (Type 1) ST segment is

(A) Horizontal (B) Elevated (C) Depressed (D) Saddleback type

Q13. In classical Brugada syndrome T wave is

(A) Flat (B) Upright (C) Inverted(D) Biphasic

Q14. ECG fi ndings of Brugada syn-drome are seen in which leads

(A) V1 & V2(B) V3 & V4(C) V3R to V6R (D) II, III, aVF

more likely to be associated with VF?

(A) J wave in inferior leads(B) J wave followed by rapid upslop-

ing ST-segment (C) J wave in setting of myocardial is-

chemia. (D) J wave recorded during sleep

Q7. Which association strongly fa-vours possibility of “early repo-larization syndrome” ?

(A) Presyncope(B) Documented idiopathic VF(C) VF in setting of acute myocardial

ischemia. (D) Inducibility of VT during electro-

physiological study.

Q8. Arrhythmogenic syncope are characterised by

(A) Presence of prodromes(B) Absence of prodromes (C) Presence of specifi c triggers(D) Urinary incontinence

Q9. VF in absence of structural heart disease can occur in

(A) Vagotonia(B) Athelets (C) Short QT syndrome(D) Exercise

Q10. Drug eff ective in suppressing

‘J’ Point


Q15. Sensitivity of ECG in diagnosing Brugada syndrome is increased by recording leads in V1 & V2

(A) 2nd intercostal space(B) 3rd intercostal space(C) 4th intercostal space (D) 5th intercostal space

Q16. Diagnosis of Brugada syndrome is made by

(A) ECG(B) Clinical profi le(C) ECG + clinical profi le(D) Electrophysiologic study

Q17. ECG manifestations of Brugada syndrome are unmasked by

(A) Sodium channel blockers(B) Fever(C) Exercise(D) Beta blockers

Q18. Which of the following is diag-nostic feature of Brugada syn-drome ?

(A) Type 2 or Type 3 ECG changes(B) Conversion of type 3 to type 2 (C) Conversion of type 2 to type 1(D) Spontaneous appearance of type 1

during sleep

type 1 Brugada like ECG ?(A) LBBB(B) Arrhythmogenic right ventricular

cardiomyopathy (C) Pectus excavatum (D) RBBBQ24. Which drugs can be useful in

management of Brugada syn-drome ?

(A) Quinidine(A) Propranolal (B) Verapamil (C) Nicorandil

Q25. Which condition can produce J wave ?

(A) Acidosis (B) Hyperkalemia (C) Hypercalcemia(D) All

Q26. Occlusion of which coronary ar-tery can produce type 1 Brugada like ECG?

(A) LAD(B) LCX(C) Distal RCA(D) Conus branch of RCA

Q19. ECG fi ndings of Brugada syn-drome are unmasked by

(A) Sodium Channel blockers (B) Calcium channel blockers(C) Potassium channel operers (D) Isoprenaline

Q20. Arrhythmias of Brugada syn-drome are suppressed by

(A) Quinidine(B) Procainamide(C) Ajmalin(D) Amiodarone

Q21. Which drugs are eff ective in con-trolling arrhythmias in Brugada syndrome ?

(A) Beta blockers(B) Cliostazole (C) Orciprenaline(D) Amiodarone

Q22. Which drug does not produce Brugada like ECG pattern ?

(A) Flecainide(B) Ajmaline(C) Quinidine(D) ProcainamideQ23. Which conditions can produce

Answers:(1) A, (2) B, (3) B, (4) A,B, (5) C, (6) C, (7) B, (8)B,D, (9)C, (10) A,C, (11)A, (12)B, (13) C, (14) A, (15) A,B, (16) C, (17) A,B, (18) C,D, (19) A,B,C, (20) A, (21)B,C, (22) C, (23) B,C,D (24)A, (25)D, (26) A,D.


PICTORIAL CME

MONIKA MAHESHWARI

Dr. Monika Maheshwari is Associate Professor at Jawahar Lal Nehru Medical College, Ajmer, Rajasthan

Coronary Artery Thrombus

Figure 2. Left coronary angiogram showing extensive thrombus of grade 5 in left anterior descending artery (LAD).

Unusual extensive intracoronary thrombus, remains a therapeutic challenge. Despite advances in interventional technology and adjunctive pharmacology, these lesions represent a substantial risk for short- and long-term complications. Periprocedural myocardial infarction, distal embolisation leading to no re-fl ow and long-term reocclusion can occur. While there is no evidence-based algorithm available for the treatment of (extensive) coronary thrombosis, a variety of techniques have been applied, including balloon angioplasty and stent placement preceded by thrombus aspiration, intracoronary thrombolytic treatment, excimer laser coronary angioplasty, bypass surgery or medical treatment including glycoprotein IIb/IIIa receptor antagonists.

Th rombus grading scales are essential tools used for quantifi cation of the throm-bus burden. Th ey provide a platform for clinical assessment and management deci-sions prior to and during interventions. Th e widely used Th rombolysis in myocardial infarction (TIMI) thrombus grading scale ranges from grade 0 (no thrombus), grade 2 (thrombus greatest dimension is <1/2 vessel diameter), grade 3 (thrombus greatest dimension ranges between >1/2 to <2 vessel), grade 4 (thrombus greatest dimension >2 vessel diameter) (Figure 1) and grade 5 (very large thrombus content that completely occludes vessel fl ow) (Figure 2).

Figure 1. Right coronary angiogram showing thrombus of grade 4 in right coronary artery (RCA).

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tions. Identify precisely all drugs and chemicals used, includ-ing generic name(s), dose(s), and route(s) of administration.Authors submitting review manuscripts should include a sec-tion describing the methods used for locating, selecting, ex-tracting, and synthesizing data. These methods should also be summarised in the abstract.Statistics: Describe statistical methods with enough detail to enable a knowledgeable reader with access to the original data to verify the reported results. When possible, quan-qfcv� ä�kafkdp� ^ka� mobpbkq� qebj � t fqe� ^mmol mof qb� fkaf ^ql op�l c� j b^pr obj bkq� bool o� l o� r k` boq fkqv� %pr ` e� ^p� ` l kä�abk` b�intervals). Avoid relying solely on statistical hypothesis test-ing, such as P values, which fail to convey important informa-tion about effect size. References for the design of the study and statistical methods should be to standard works when ml ppf_ib�%t fqe�m dbp�pq qba&+�Abä�kb�pq qfpqf î�qboj p)�^__ob*viations, and most symbols. Specify the computer software used.Results: Present your results in logical sequence in the text, tables, and illustrations, giving the main or most important ä�kafkdp� ä�opq+� Al � kl q� obmb^q� îi� qeb� a^q � fk� qeb� q _ibp� l o� fi*lustrations in the text; emphasise or summarise only the most important observations. Extra or supplementary materials and technical detail can be placed in an appendix where they t fii� _b� ^` ` bppf_ib� _r q� t fii� kl q� fkqboor mq� qeb� ã�l t � l c� qeb� qbuq)�or they can be published solely in the electronic version of the journal.When data are summarised in the Results section, give nu-meric results not only as derivatives (for example, percent-ages) but also as the absolute numbers from which the de-rivatives were calculated, and specify the statistical methods r pba� ql � ^kîvpb� qebj +� Obpqof q� q _ibp� ^ka� ä�dr obp� ql � qel pb�needed to explain the argument of the paper and to assess supporting data. Use graphs as an alternative to tables with many entries; do not duplicate data in graphs and tables. Avoid nontechnical uses of technical terms in statistics, such as “random” (which implies a randomising device), “normal,” Üpfdkfä�` ^kq)î�Ü l oobi^qfl kp)î�^ka�Üp^j mib+îT ebob�p` fbkqfä�` îiv�^mmol mof qb)�^kîvpbp�l c�qeb�a^q �_v�pr ` e�variables as age and sex should be included.Discussion: Emphasise the new and important aspects of the study and the conclusions that follow from them in the context of the totality of the best available evidence. Do not repeat in detail data or other information given in the Introduction or the Results section. For experimental studies, it is useful ql �_bdfk�qeb�afp` r ppfl k�_v�_ofbã�v�pr j j ôfpfkd�qeb�j ^fk�ä�ka*ings, then explore possible mechanisms or explanations for qebpb�ä�kafkdp)� ` l j m ob�^ka� ` l kqo pq�qeb�obpr iqp� t fqe� l qebo�relevant studies, state the limitations of the study, and ex-mil ob�qeb�fj mif ^qfl kp�l c�qeb�ä�kafkdp�cl o�cr qr ob�obpbô e�^ka�for clinical practice.Link the conclusions with the goals of the study but avoid r knr îfä�ba�pq qbj bkqp�^ka�` l k` ir pfl kp�kl q�âbnr ^qbiv�pr m*ported by the data. In particular, avoid making statements on b` l kl j f �_bkbä�qp�^ka�` l pqp�r kibpp�qeb�j ^kr p` ofmq�fk` ir abp�the appropriate economic data and analyses. Avoid claiming priority or alluding to work that has not been completed. State new hypotheses when warranted, but label them clearly as such.Examples:1. Malik V, Roy D. Management of locally advanced breast

cancer. Cardiology Today 1997;2(5):45-51.(for Journal)2. Sambasivan M. References to central nervous system in

the ancient texts: In: S. Venkatraman (ed). Progress in Clinical Neurosciences, 11th Ed, Mediworld Publications 1996:116-118. (for Chapter in a Book)

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Cardiology TodayCover May-June 2017 - CIMS · Dr. Monica Bhatia EDITOR IN CHIEF OP Yadava SECTION...

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