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April 2018Volume 9 No 1

Cardiology Newsletter

• Cryptogenicstrokeandatrialfibrillation:Whatisthelink?

• Bloodpressuretargets:ImplicationsofthenewAmericanHeartAssociation(AHA)HypertensionGuidelines

• STEMI:S-TElevationMyocardialInfarction

• Hearttransplantation

SAZA.SA.18.02.0072

Assuring Originator Qualit

y

Helps save lives1

When quality, efficacy2 and cost3 matter

Due to its possible, substantial toxicity, Arycor® is only intended for use in patients with the indicated life-threatening arrhythmias.

References: 1. Arycor® Package Insert. February 2007. 2. Connolly SJ. Evidence-Based Analysis of Amiodarone Efficacy and Safety. Circulation 1999;100:2025-2034. 3. South African Medicine Price Registry. Database of Medicine Prices 20th May 2016. Available at: http://www.mpr.gov.za/PublishedDocuments.aspx. Accessed June 2016.SCHEDULING STATUS: S4 PROPIETARY NAME (and dosage form): ARYCOR® 100 (tablets); ARYCOR® 200 (tablets). COMPOSITION: ARYCOR® 100 tablets: Each tablet contains 100 mg amiodarone hydrochloride. ARYCOR® 200 tablets: Each tablet contains 200 mg amiodarone hydrochloride. PHARMACOLOGICAL CLASSIFICATION: A.6.2.Cardiac depressants. REGISTRATION NUMBERS: ARYCOR® 100: 32/6.2/0513. ARYCOR® 200: 32/6.2/0514.

For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority.

Marketed by Zentiva, a sanofi company. Applicant: Winthrop Pharmaceuticals (Pty) Ltd, a sanofi company. Reg. no. 1931/002901/07. Sanofi House, 2 Bond Street, Grand Central Ext. 1 Midrand 1685. Tel: (011) 256 3700. Fax: (011) 256 3707. www.zentiva.com.SAZA.GAMD.16.05.041810

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10908 Arycor ADVERT.indd 1 2016/07/01 4:09 PM

Volume 9 No 1 April 2018

Dr Adrian HorakCardiologist

Vincent Pallotti Hospital, Pinelands, Cape Town

e certainly are living in “interesting times”. There are so many new d e v e l o p m e n t s occurring on all fronts

(political, economic and medical). There is however one constant of which we can be certain and that is that things will always be changing. Indeed, I have heard it said that the half-life of medical knowledge is about 6 months. If we are not constantly keeping abreast of the changes, we will certainly be out of date within 6 months and we will be woefully inadequate within a year. This alone is enough incentive for us to keep striving for excellence.

This issue of Heart Matters presents 4 articles, all of which underline significant changes which have been occurring in different aspects of cardiology.

In his article on STEMI, Dr Adriaan Snyders presents data on the changing landscape of STEMI which is now the new epidemic to be faced by Sub-Saharan Africa. Measures are being made to put in place the STEMI project in order to improve recognition, treatment and outcomes of STEMI. This project certainly deserves full recognition and has the potential of having major impact on the mortality and morbidity of patients suffering from STEMI.

people. The goalposts are constantly changing but Professor Brian Rayner presents an excellent overview of the latest hypertension guidelines from the American Heart Association and he gives his own personal insights as to how these should be applied and how BP should be accurately measured.

Stroke is yet another debilitating condition. Recent developments have outlined the importance of atrial fibrillation as an etiologic factor for cryptogenic stroke. Dr Mike Allison’s succinct and insightful article on recognising and diagnosing subclinical atrial fibrillation and the approach to cryptogenic stroke highlights the importance of diagnosing atrial fibrillation and the mechanisms that we have to bring this matter to light. New technologies, such as the implantable loop recorder (ILR) are now gaining huge prominence.

Finally, we revisit heart transplantation. The 50th anniversary of the first heart transplant was celebrated last year. Professor Johan Brink has an overview of the state of the art of heart transplantation currently worldwide and in South Africa.

We trust that this issue of Heart Matters will be stimulating and will also assist in keeping us abreast of all the constant changes which are occurring in our wonderful profession.

DisclaimerThe content contained in this publication contains medical or health sciences information and is intended for professional use within the medical field. No suggested test or procedure should be carried out unless, in the reader’s judgement, its risk is justified. Because of rapid advances in the medical sciences, we recommend that the independent verification of diagnoses and drug dosages should be made. Discussions views, and recommendations as to medical procedures, products, choice of drugs, and drug dosages are the views of the authors. The views expressed by the editor or authors in this newsletter do not necessarily reflect those of the sponsors or publishers. The sponsors, publishers and editor will not be liable for any damages or injuries of any kind arising from the use or misuse of information provided in this publication and do not support the use of products for off label indications.

If you have any suggestions or topics you would like to see published or have articles and/or

case studies for publishing, please email us at: [email protected].

Production Editors: Ann Lake, Helen Gonçalves Design: Jane Gouveia

Enquiries: Ann Lake Publications 011 802 8847 Email: [email protected]

Editorial

Constant Change

Dr Adrian HorakCardiologist, Vincent Pallotti Hospital, Pinelands, Cape Town

Assuring Originator Qualit

y

Helps save lives1

When quality, efficacy2 and cost3 matter

Due to its possible, substantial toxicity, Arycor® is only intended for use in patients with the indicated life-threatening arrhythmias.

References: 1. Arycor® Package Insert. February 2007. 2. Connolly SJ. Evidence-Based Analysis of Amiodarone Efficacy and Safety. Circulation 1999;100:2025-2034. 3. South African Medicine Price Registry. Database of Medicine Prices 20th May 2016. Available at: http://www.mpr.gov.za/PublishedDocuments.aspx. Accessed June 2016.SCHEDULING STATUS: S4 PROPIETARY NAME (and dosage form): ARYCOR® 100 (tablets); ARYCOR® 200 (tablets). COMPOSITION: ARYCOR® 100 tablets: Each tablet contains 100 mg amiodarone hydrochloride. ARYCOR® 200 tablets: Each tablet contains 200 mg amiodarone hydrochloride. PHARMACOLOGICAL CLASSIFICATION: A.6.2.Cardiac depressants. REGISTRATION NUMBERS: ARYCOR® 100: 32/6.2/0513. ARYCOR® 200: 32/6.2/0514.

For full prescribing information, refer to the package insert approved by the Medicines Regulatory Authority.

Marketed by Zentiva, a sanofi company. Applicant: Winthrop Pharmaceuticals (Pty) Ltd, a sanofi company. Reg. no. 1931/002901/07. Sanofi House, 2 Bond Street, Grand Central Ext. 1 Midrand 1685. Tel: (011) 256 3700. Fax: (011) 256 3707. www.zentiva.com.SAZA.GAMD.16.05.041810

908

10908 Arycor ADVERT.indd 1 2016/07/01 4:09 PM

At the end of his article, Dr Snyders includes a number of unrelated “health tips” which are based on his extensive experience and are certainly well worth reading. Hypertension is another problem which impacts the health and wellbeing of the massive numbers of

Stroke is yet another debilitating condition. Recent developments have outlined the importance of atrial fibrillation as an etiologic factor for cryptogenic stroke.


Cryptogenic stroke and atrial fibrillation: What is the link?

Dr Mike AlisonCardiologist, Sunninghill Hospital, Johannesburg

troke is a leading cause of mortality and serious long-term disability. Patients with atrial fibrillation (AF) are at especially high risk. In the presence of AF

the risk of ischaemic stroke increases five-fold and in comparison to non-AF-related strokes, the risk of mortality doubles. In contrast, anticoagulation in patients with AF reduces the risk of stroke by 67%.1

Cryptogenic stroke is defined as brain infarction not clearly attributable to a definite cardioembolism, large artery atherosclerosis or small artery disease, despite extensive investigation.

In the USA, approximately 200 000 cryptogenic strokes occur annually, accounting for approximately 30% of all ischaemic strokes. Most occur in patients who are receiving antiplatelet therapy for secondary prevention.

Long-term monitoring reveals atrial fibrillation (AF) in approximately 30% of patients with cryptogenic stroke - patients who would have benefitted from anticoagulant therapy. In these individuals, the risk of recurrent stroke is high, where up to 20% will have a second stroke within 4 years of the initial event.

Diagnosis of cryptogenic stroke is one of exclusion. Investigations include brain CT/MR, 12-lead ECG, precordial electrogram, extra- and intravascular imaging and cardiac monitoring for at least 24 hours. Nevertheless, unless the patient has an episode of AF during the assessment, that diagnosis is likely to be missed.

Monitoring to detect AF after cryptogenic strokeConventional monitoring strategies may not be sensitive enough to detect AF, especially since up to 80% of AF episodes

Figure 1. Time to first detection of atrial fibrillation in the CRYSTAL AF study.Adapted from Sanna T, et al. N Engl J Med 2014; 370(26): 2478-2486.2

are asymptomatic. Patient compliance with Holter monitors and event recorders is poor and, although it may be improved with mobile cardiac telemetry, given the paroxysmal nature of AF, a duration of monitoring limited to 30 days may not be sufficient.

Long-term monitoring with insertable cardiac monitors (ICM) may increase the detection of AF. The CRYSTAL AF study randomised 441 patients with a diagnosis of cryptogenic stroke and no evidence of AF during at least 24 hours of ECG monitoring to either an insertable (REVEALTM) cardiac monitor or conventional follow up.2 The primary endpoint was time to first detection of AF at 6 months. Secondary endpoints included time to first detection of AF at 12 months, recurrent stroke or transient ischaemic attack (TIA) and change in use of oral anticoagulant drugs.

By 6 months, AF had been detected in 19 patients (8.9%) in the ICM group and 3 patients (1.4%) in the control group (hazard ratio, HR 6.4; CI95% 1.9-21.7;


P<0.001). Rates of detection at 12 and 36 months were 2.4% vs. 2.0% and 30.0% vs. 3.0% in the ICM and control groups, respectively (Figure 1).

In the ICM group, the median time from randomisation to detection of AF was 41 days (interquartile range 14-84 days) at 6 months and 84 days (interquartile range 18-265 days) at 12 months. Seventy nine percent of first episodes were asymptomatic during the first year.

By 12 months, 97% of patients in whom AF was detected were receiving oral anticoagulants. Ischaemic stroke or TIA occurred in 15 patients (7.1%) in the ICM group as compared with 19 patients (9.1%) in the control group.

Of 208 ICMs that were inserted, 5 (2.4%) were removed due to infection of the insertion site or pocket erosion. The device remained inserted in 98% of patients at 6 months and 97% at 12 months.

Numerous additional studies of ICM mirror these observations from the CRYSTAL AF study, with AF detection yields of up to 33% and median times to detection ranging from 48 to 161 days.3-7

Similar observations have also been documented in real-world clinical practice. Using data from the de-identified Medtronic DiscoveryLink™ database, AF detection rates (episodes ≥2 minutes) were quantified using Kaplan-Meier survival estimates at 1 and 6 months for patients who received an ICM (Reveal LINQ™) for the purpose of AF detection following a cryptogenic stroke.8 Eighty five patients were monitored for a mean of 569 days and paroxysmal AF was detected by ICM in 16% at a mean of 109 days after stroke onset. In all cases, AF was asymptomatic and occurred in episodes lasting predominantly between 1 and 4 hours. Four patients suffered recurrent stroke, 3 of whom had AF and were on oral anticoagulation.

Used with permission from Matthew C. Holtzman, MD. Neurology Michigan P.C. This pathway represents Dr. Holtzman’s clinical practice. Medical judgment should be used to determine if adopting pathway is appropriate.

STROKE

Lacunar infraction: small vessel disease

Embolic appearing stroke with no history of AF: • Multiple foci of infarction • Cortical watershed

distribution • Cerebellar

History of AF?

Standard stroke work-up

Standard stroke work-up

Antiplatelet agent Anticoagulation Standard stroke work-up

MRA or CTA of intracranial vessels Transesophageal Echocardiogram (TEE)

Symptomatic carotid stenosis greater than 50%

Intracranial stenosis Positive TEE All testing

negative?

CEA or stent Anticoagulant No medical contraindications

to insertion

Refer patient for ILR insertion

Multifocal Monofocal

Medical management Antiplatelet agents

Angiogram Lumbar puncture Vasculitis work-up

Figure 2. A suggested algorithm for management of a patient with ischaemic stroke and the place of ICM.Standard stroke workup includes carotid dopplers, telemetry bed, fasting lipogram, glucose control, blood pressure management and

hypercoagulation screen (if age <50 years). From http://www.medtronicdiagnostics.com.9

Where does ILR fit in the pathway for ischaemic stroke?

Overall, the message from these studies is clear: AF is common and the majority of first episodes are asymptomatic. Short- and intermediate-term monitoring may miss many patients with paroxysmal AF, whereas diagnosis is much more likely with long-term continuous monitoring.

In CRYSTAL AF, ICM reduced the incidence of stroke by approximately 40 per 1000 patients and improved quality-adjusted life years (QALYs). The probability that the ICM strategy would be cost-effective under a threshold of 30 000 Euros per QALY was 81%, and cost-effectiveness is likely to be greater in patients with higher CHADS score.

A suggested management algorithm when considering ICM insertion is illustrated in Figure 2.

This article was first published in Neuron SA Special Review Edition 2017.

References on request.


Blood pressure targets: Implications of the new American Heart Association (AHA) Hypertension Guidelines

rior to 2009 there was unanimity on blood pressure (BP) targets in all major guidelines. For uncomplicated essential hypertension it was

< 140/90 mmHg and for high risk patients, diabetics and those with established cardiovascular disease (CVD) < 130/80 mmHg.1 However, in 2009 in a reappraisal of the European Society of Hypertension Guidelines the authors found no evidence to suggest the lower target for high risk patients.2 For example, in patients with diabetes no study that randomised patients to conventional vs. intensive targets showed benefit in lowering BP to < 130/80 mmHg. There were also several observational studies to suggest that there was a U-shaped relationship between BP and outcome with patients with both low and high systolic and diastolic had worse CV outcomes.3,4 Low diastolic BP was of special concern as myocardial perfusion occurs during diastole and this could be potentially compromised especially in those with coronary artery disease and left ventricular hypertrophy. The major drawback of observational studies is that they suffer from bias, unaccounted confounding factors and reverse causality i.e. the low BP was a manifestation of underlying cardiac disease.

In view of these concerns major guidelines in 2013 and 2014 revised BP targets and abandoned the lower target for patients with diabetes and high CV risk.5-7 All major guidelines now recommended a unitary target of < 140/90 mmHg for all hypertensives apart from the elderly where this was increased to < 150/90 in the elderly in 2 of these publications.5,7

The SPRINT and ACCORD studiesThe only scientific way to determine BP targets is to conduct a randomised controlled trial that randomises patients to conventional or intensive BP targets.

With this in mind two major studies the ACCORD and SPRINT were planned and conducted to test the hypothesis that lower targets resulted in superior outcomes without adverse effects.

The SPRINT Study enrolled patients with hypertension > 50 years at higher CV risk without diabetes, but including those with chronic kidney disease (CKD), with a systolic BP between 130 - 180 mmHg. Patients were randomised to intense control BP control (< 120 mmHg) vs. usual control (< 140mm Hg).8 Importantly evidence based antihypertensive drugs namely diuretics, calcium channel blockers and ACE inhibitors/angiotensin receptor blockers were recommended.

The study was stopped prematurely because in the intensive arm there was significant reduction in major adverse cardiovascular events (MACE) (hazard ratio (HR) 0.75 (0.64 - 0.89), p<0.001) particularly in CV mortality (HR 0.57 (0.38 - 0.85), p = 0.005) and heart failure (HR 0.62 (0.45 - 0.84), p = 0.002). There was no signal for increased myocardial infarction (HR 0.83 (0.64 - 1.09), p = 0.13). Benefit was seen in all subgroups but importantly there was no adverse signal in patients > 75 years even if they were frail.

The ACCORD study was a similar study conducted in diabetics at higher CV risk but included an intensive glucose lowering arm.9 In this study there was a non-significant reduction in MACE (HR 0.88 (0.73 -1.06), p = 0.2) but no signal for increased non-fatal myocardial infarction (HR 0.87 (0.68 - 1.10), p = 0.25). There was also a small but significant reduction in non-fatal stroke (HR 0.63 (0.41 - 0.96), p = 0.03) and fatal stroke (HR 0.59 (0.39 - 0.89, p = 0.01). ACCORD differed from SPRINT in 2 important respects. ACCORD was underpowered to meet the study objectives and secondarily there was significant more use β-blockers in the

intensively treated arm. Sub-analysis of the study suggested an interaction between β-blockers, hypoglycaemia and adverse CV outcomes.10

On the flip side important adverse were reported in SPRINT and ACCORD mostly attributed to too low BP and off target side effects of antihypertensive treatment. These were dizziness, falls, syncope, electrolyte abnormalities, bradycardia (ACCORD only) and acute kidney injury. However, there were no injurious falls, no excess of patients requiring acute or chronic dialysis for end stage chronic kidney disease in the intensively treated group. These adverse effects are predictable and reversible by adjustment of antihypertensive therapy.

The major controversy arising from ACCORD and especially SPRINT was the way the BP was measured. This was done by automated devices and a mean of 3 readings were taken. In SPRINT the measurements were unobserved. This method of BP measurement is termed automated office blood pressure (AOBP) and more accurately reflects day time ambulatory BP by reducing the white coat effect.11 It also correlates better with target organ damage than conventional office BP.11 Office BP in the standard clinical setting is inaccurate in up to 30% of cases often due to deviations from the recommended procedure. Furthermore, the white effect is often exaggerated especially in elderly patients. For example, in the HYVET study performed in patients > 80 years the difference between conventional office systolic BP and day time mean ambulatory BP in was 36 mmHg!12

In the author’s opinion it is critical that an accurate assessment BP is undertaken especially if intensive targets of BP are being considered to balance the benefits vs. adverse effects described in SPRINT and ACCORD. This was must be done by routinely using a combination of AOBP, self BP monitoring and 24-hour ambulatory monitoring.

Professor Brian RaynerDivision of Nephrology and Hypertension, University of Cape Town


The New AHA Hypertension GuidelinesIn January 2018 the AHA Hypertension were published in Hypertension.13 This was a major overview on the management of hypertension, and there were 2 fundamental changes in recommendations from previous guidelines. These were the definitions of hypertension and target BPs.

Hypertension was defined as a BP ≥ 130 or 80 mmHg and normal BP < 120 and 80 mmHg. (Table 1) An algorithm for the treatment and follow up of patients is shown in Figure 1, and target BP in Table 2. It is important to note that for adults with confirmed hypertension and known CVD or atherosclerotic CVD event risk > 10% a BP target < 130/80 is strongly recommended and includes patients with diabetes even though the ACCORD study did not meet its primary endpoint. However, in those without additional markers of increased CVD risk the recommendation for target BP < 130/80 is more muted and considered reasonable. There is no study that has tested targets in this group.

The reader is referred to the full publication for further information.

Should I adopt the new AHA Hypertension Guidelines in my practice?The South African Hypertension Practice guidelines published in 20141 are unlikely to be updated in the next 12 months and recommended a standard target of < 140/90 mmHg in all hypertensive patients. The new Canadian Hypertension Guidelines recommends a target of < 120/80 mmHg in those patients meeting the SPRINT entry criteria.11

The AHA recommends a target BP of < 130/80 mmHg for all hypertensives including diabetics.13 The slightly higher target is presumably recommended as analysis of the results of SPRINT showed that in weighing risks vs. benefits the best results were achieved at a systolic BP of 132 mmHg.8

In the author’s view the AHA new definitions and targets for hypertension are to be supported, but there needs to be a fundamental change in our practice especially in relation to BP measurement.

Table 1. Classification of hypertension according to the AHA Hypertension Guidelines

BP Category* SBP DBP

Normal <120 and <80

Elevated 120-129 and <80

Hypertension

Stage 1 130-139 or 80-89

Stage 2 ≥140 or ≥90

*Individuals with SBP and DBP in 2 categories should be designated to higher. BP based on ≥2 careful readings obtained on ≥2 occasions

Table 2. BP targets according to the AHA Hypertension Guidelines

Level of recommendation BP Goal for Patients with Hypertension

IFor adults with confirmed hypertension and known

CVD or ASCVD* event risk > 10% a BP target < 130/80 is recommended

IIbFor adults with confirmed hypertension without additional markers of increased CVD risk a BP target < 130/80 maybe

reasonable

*ASCVD = atherosclerotic cardiovascular disease

Figure 1. BP thresholds and recommendations for treatment and follow up*HT = hypertension; Class refers to level of recommendation


Practitioners should invest in a quality automated BP device that is durable for high volumes of BP measurements. AOBP should be instituted in the practice and the diagnosis and target BPs based on the mean of stable three readings. In addition, there should be more frequent visits and attention must be paid to symptoms of hypotension like dizziness, sexual dysfunction, postural hypotension, unexplained feelings of anxiety and tiredness. Kidney function and electrolytes need to be monitored more regularly to detect deterioration in kidney function and electrolyte abnormalities.

Assessment of BP must also be combined with self BP and ambulatory BP measurement. Adjustment of treatment must be based on these assessments.

Whether this is appropriate in the public sector at present is a matter for debate. In the author’s view AOBP saves considerable physician time enabling the practitioner to spend more time with the patient. This in fact may benefit patients in very busy public-sector clinics, and we have been doing this at the Hypertension Clinic at Groote Schuur Hospital for more than 15 years. Investing in automated BP devices in public sectors clinics should be a priority for health authorities.

If AOBP is unavailable to the practitioner and conventional office BP is performed, then in the author’s view a target of BP < 140/90 mmHg is more appropriate for the reasons outlined above regarding accuracy and white coating.

ConclusionsThe AHA Hypertension guidelines is ma-jor departure from previous definitions of hypertension and target BP and are reasonably evidence based. It is recom-mended that practitioners adopt these new norms especially if access to AOBP, self and ambulatory BP is readily avail-able. There is no increased risk of ad-verse CV events. Kidney function and electrolytes need to be monitored more frequently and careful attention paid to symptoms of hypotension.

References1. Seedat YK, Rayner BL, Veriava Y.

South African hypertension practice guideline 2014. Cardiovascular journal of Africa 2014; 25(6): 288-94.

2. Mancia G, Laurent S, Agabiti-Rosei E, et al. Reappraisal of European guidelines on hypertension management: a European Society of Hypertension Task Force document. Journal of hypertension 2009; 27(11): 2121-58.

3. McEvoy JW, Chen Y, Rawlings A, et al. Diastolic Blood Pressure, Subclinical Myocardial Damage, and Cardiac Events: Implications for Blood Pressure Control. Journal of the American College of Cardiology 2016; 68(16): 1713-22.

4. Vidal-Petiot E, Ford I, Greenlaw N, et al. Cardiovascular event rates and mortality according to achieved systolic and diastolic blood pressure in patients with stable coronary artery disease: an international cohort study. Lancet (London, England) 2016; 388(10056): 2142-52.

5. 2013 Practice guidelines for the management of arterial hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology (ESC): ESH/ESC Task Force for the Management of Arterial Hypertension. Journal of hypertension 2013; 31(10): 1925-38.

6. Weber MA, Schiffrin EL, White WB, et al. Clinical practice guidelines for the management of hypertension in the community a statement by the American Society of Hypertension and the International Society of Hypertension. Journal of hypertension 2014; 32(1): 3-15.

7. James PA, Oparil S, Carter BL, et al. 2014 evidence-based guideline for the management of high blood pressure in adults: report from the panel members appointed to the Eighth

Joint National Committee (JNC 8). Jama 2014; 311(5): 507-20.

8. Wright JT, Jr., Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. The New England journal of medicine 2015; 373(22): 2103-16.

9. 9. Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. The New England journal of medicine 2010; 362(17): 1575-85.

10. Tsujimoto T, Sugiyama T, Shapiro MF, Noda M, Kajio H. Risk of Cardiovascular Events in Patients With Diabetes Mellitus on beta-Blockers. Hypertension 2017; 70(1): 103-10.

11. Leung AA, Daskalopoulou SS, Dasgupta K, et al. Hypertension Canada’s 2017 Guidelines for Diagnosis, Risk Assessment, Prevention, and Treatment of Hypertension in Adults. The Canadian journal of cardiology 2017; 33(5): 557-76.

12. Bulpitt CJ, Beckett N, Peters R, et al. Does white coat hypertension require treatment over age 80?: Results of the hypertension in the very elderly trial ambulatory blood pressure side project. Hypertension 2013; 61(1): 89-94.

13. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Hypertension 2017.

Key points:

• The AHA Hypertension guidelines have redefined the definition of hypertension and lowered target BP to < 130/80 mmHg in all patients

• Accurate assessment of BP is essential in adopting these new guide-lines, and AOBP, self and ambulatory BP should be included in patient management

• Careful attention needs to be paid to symptoms of hypotension, and kidney function and electrolytes need to be monitored more regularly to avoid adverse effects of the lower targets.


TEMI is an important diagnosis, potentially fatal, not difficult to diagnose and be treated effectively, thus saving lives and improving morbidity. Being the

core of acute coronary syndrome (ACS) and coronary artery disease, it ranks number one under non-communicable diseases in South Africa. Despite the presence of HIV and other infections, this will soon be the case in the rest of Africa.

Until recently, we were not doing well in managing STEMI. In public health, 60% of patients do not receive appropriate therapy in time, and 30% of those who die of STEMI could have been saved if treated according to the international guidelines. Understanding the diagnosis and treatment of STEMI also assists in treating patients with ACS and those who present with chest pain.

We know how to diagnose and treat STEMI, why then are we failing, considering that many documents and guidelines are available and frequently discussed? Our STEMI management systems fail to provide the necessary care. Vital to improving STEMI management is at the first medical contact (FMC), where the diagnosis needs to be made immediately including timely medication and transfer to a central capable hospital. In STEMI management, the clinic doctor, professional nurse and healthcare workers, porters, administrators and emergency services play a more important role than the specialist.

The South African Heart Association (SA Heart) and South African Society of Cardiovascular intervention (SASCI) run a project called “STEMI SA – Time is Muscle”, working with the international project “Stent Save a Life” to improve systems of care and particularly assist those at the FMC. Should there be a need for more information about educational opportunities or you wish to participate/

contribute to this programme, you are invited to locate the STEMI SA activities’ link and contact details on the www.SASCI.co.za website.

Typical chest pains are central to the diagnosis of STEMI. A central retrosternal, pressing, burning, discomfort spreading to the shoulder, neck, jaw and left arm associated with sweating, nausea and dizziness can hardly be anything else than myocardial infarction. Atypical chest pains, however, do not exclude the presence of an infarct, particularly in high-risk patients and those who have already had an event. Certain females are unique, so be careful not to miss an infarct when they present with symptoms one cannot explain! Any person experiencing similar symptoms should immediately seek medical assessment.

Management most often goes astray at the FMC. All patients with chest pains should immediately have an ECG done. Clear S-T elevation, particularly with a typical history, is all that is needed to make the diagnosis. No need to wait for blood results or chest X-rays. Apart from routine resuscitation therapy, a decision as to how to reperfuse the blocked coronary artery must be taken. Any reperfusion beyond 120 minutes of artery blockage will save very little heart muscle from undergoing necrosis. The guidelines are clear.

The guidelines on this are clear:• If the symptoms started within less than

60 minutes and the patient can be at a cath lab for primary intervention, this strategy should be followed. Direct communication with the treating cardiologist and emergency healthcare workers would be needed. If the transfer time to the cath lab is more than 30 minutes, alternative therapy is indicated.

• If this is not possible or the pain per-sists for more than 6–12 hours or comes and goes, thrombolysis needs to be ad-

ministered if no contraindications are present. Administering thrombolysis requires knowing the indications and contraindications. Thrombolysis should be available, and confidence in ad-ministering exist at FMC. Assistance is only a phone call away, and you should know whom to phone.

STEMI SA can provide a wall poster guiding you through the algorithm and is finalising a one-day training course that will be presented at centres participating in our drive. This initiative for speedy, appropriate systems to open a blocked coronary artery, saves lives leaving the victim with a much better prognosis to continue working and being part of the economy for years to come.

To make a difference, healthcare workers at FMC need to be competent in taking and interpreting an ECG. The STEMI SA training course will assist in doing just that. To treat STEMI efficiently, having thrombolytics available should not be an option but obligation. Adjunctive therapy includes aspirin 300 mg, low-molecular-weight heparin 30–40 mg IV and 60–80 mg subcutaneous, and clopidogrel 300 mg. A beta-blocker like bisoprolol 5 mg, if not contraindicated, is not as critical as thought previously but still recommended. Oxygen is only necessary when needed with low O

2 saturation.

Morphine is given only in the presence of severe pain and discomfort but beware of nausea. Observe restless patients with/without neurologic derangement and those with a very weird-looking ECG. Do not turn your back as you may need to start resuscitation. Consider ventilation if the patient is very restless. Knowledge about the renal function is important. Nevertheless, blood tests should not delay treatment. When in a central hospital, statin will be given.

What if you do not have thrombolysis and cannot have your patient at a cath lab in less than 30 minutes? The patient will surely suffer damage to the heart muscle because effective management was not available. Be informed and confident to manage the STEMI and have the

STEMI: S-T Elevation Myocardial Infarction

Dr Adriaan Snyders Cardiologist, Wilgers Hospital, PretoriaSTEMI SA National Co-ordinator and Regional co-ordinator for Stent Save a Life Africa


necessary medication at hand to avoid contributing to unnecessary morbidity. In such a case do what you can, i.e. administer the adjunctive medication and transfer to a centre capable of managing STEMI – preferably a cath lab as soon as possible. Know where to find a cath lab and whom to contact.

What if thrombolysis was administered? After haemodynamically stabilising the patient, transfer him/her to a cath lab hospital as soon as possible. Thrombolysis is not the end of therapy. Follow-up angiography is necessary even if reperfusion occurred, as reperfusion may not be optimal with adequate free coronary flow (TIMMI III) an assessment of the other arteries is important for future management. If angiography is not done within 24 hours of the event, only ischaemia-driven interventions would be of any benefit.

Post-coronary intervention management includes optimised medication, good lifestyle counselling, physical activity and regular evaluation. Target LDL cholesterol needs treatment to a level <1,8 mmol/L. Smoking is out, i.e. not negotiable! The early morning blood pressure reading, before medication, should be 130/80 mmHg in hypertensive cases. Regular, moderate exercise is the key to a symptom- and event-free future.

With effective management, the patient can be home and return to everyday life within a short time. However, delaying treatment causes frequent complications, which include renal impairment, pneumonia, decreased functional status, depression and emotional strain, and unfortunately also creating medically unfit persons who become a burden to others.

To summarise the Key Rules• Educate patients to recognise STEMI

symptoms and understand the urgency of immediate treatment.

• Patients should preferably contact EMS (Emergency Medical Services) and/or go to the nearest PCI-capable hospital or emergency room .

• Immediately perform an ECG on all patients presenting with chest pain unless a very clear alternative cause is obvious.

S A # H E A R T # E A R L Y # R E P E R F U S I O N # P I L O T # P R O J E C T#

Symptoms,of,a,heart,aBack,Most#typical#discomfort/pain#

zones#

Other#possible#discomfort/pain#

zones#

There#may#be#a#rapid,#weak#pulse#

Sharp#stabbing#pain#in#the#leM#side#of#the#chest#is#usually#NOT#heart#pain##

This#may#feel#like#indigesAon,#spread#to#shoulders,#arms,#neck#or#jaw#and/or##last#for#more#than##15#minutes.##It#may#stop#or##weaken#and##then#return#SweaAng,#sickness,#

faintness#or#shortness#of#breath#may#be#experienced#

hRp://www.hearToundaAon.co.za/howUyourUheartUworks/symptomsUheartUaRack#(accessed#on#7#Feb#2013#

Heavy#pressure,#Aghtness,#crushing#pain#or#unusual#discomfort#in#the#centre#of#the#chest#

Symptom onset


• Healthcare professionals should be able to diagnose STEMI, based on clinical observations and supported by ECG findings.

• Healthcare professionals should be familiar with the treatment options for STEMI and immediately commence appropriate therapy, depending on the time of onset of pain and the PCI-capability of the hospital. Transfer of the patient to a PCI-capability hospital for rescue PCI should be considered.

• Tenecteplase, actilyse or streptokinase should be available at all second-ary healthcare facilities for primary thrombolysis.

• Healthcare professionals should have access to a cardiologist or other trained professionals to assist with decision making and appropriate transfer.

• All specialist facilities should contribute to the SA Heart/SASCI STEMI Early Reperfusion Registry to monitor treatment and outcome of STEMI cases for the optimisation of STEMI care nationally.

A Few Heart Health Tips from my back pocket• Everyone needs to spend time to

ensure that he/she obtains a good cardiovascular health prognosis.

• Exercise at least 3–5 hours per week.• If smoking, you are wasting your time.• Spend time to monitor your blood

S A H E A R T S A S C I E A R L Y R E P E R F U S I O N P R O J E C T

http://www.heartfoundation.co.za/how-your-heart-works/symptoms-heart-attack (accessed on 7 Feb 2013)SYMPTOMS OF A HEART ATTACK

This may feel like indigestion, spread to shoulders, arms, neck

or jaw and/or last for more than

15 minutes. It may stop or weaken and then return.

There may be a rapid, weak

pulse

Sharp stabbing pain in the left side

of the chest is usually NOT

heart pain

Heavy pressure, tightness, crushing

pain or unusual discomfort in the

centre of the chest

Sweating, sickness, faintness

or shortness of breath may be experienced

most typical discomfort / pain zones

other possible discomfort / pain zones

Symptoms in women are often different than in men. Women are more likely to experience nausea, dizziness, and anxiety.

Important Telephone Numbers Ambulance

Time to reperfusion is critical

082 911 / 10111

Diagnose with 12 lead ECG immediately (< 10 min)

STEMI diagnosis

Successful Fibrinolysis

Preferably < 30 min

Reference: 1. ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation, European Heart Journal (2012) 33, 2569–2619 doi:10.1093/eurheartj/ehs215

Monitor every 10 min if chest pain persists

Primary-PCI capable centre EMS or non-primary-PCI capable centre

Immediate Fibrinolysis“Drip & Ship”

Preferably 3-24 hours

Primary-PCI

Coronary angiography

YES NO

Rescue PCI

Immediately

• LBBB• Ventriular paced rhythm• Patients without diagnostic ST-segments

elevation but with persistent ischaemic symptoms

• Isolated posterior myorcardial infarction• ST-segment elevation in lead aVR

EMS = Emergency Medical System; FMC = First Medical Contact; PCI = Percutaneous Coronary Intervention; STEMI = ST-Segment Elevation Myocardial Infarction

Preferably < 60 min

Immediate transfer to PCI center

For PCI as soon as possible

Transfer to PCI centre as soon as possible

Patient has chest pain

PCI possible in < 120 min?

NO

YES

Preferably ≤ 90 min / ≤ 60 min for early presenters

Atypical ECG presentations requiring prompt management

This project was made possible by an educational grant from the following companies

pressure, glucose and cholesterol levels.• Early morning blood pressure readings

should not be more than 135/85 mmHg before taking medication.

• LDL cholesterol above 4 mmol/L car-ries a high risk. With cardiovascular risk factors like hypertension this should be less than 3 mmol/L; having diabetes, this should be less than 3,5 mmol/L. If you al-ready have had a cardiovascular event, the LDL should be less than 1,8 mmol/L.

• Get enough hours of sleep but rise early.• Take time to finish your meals, do not

rush!• Recognise danger signs in time.• Any symptoms, even if benign but

progressive or associated with others or affecting your quality of life, are serious and should be reported to your doctor.

• Any symptom that improves or does not worsen with activity is unlikely to be significant.

• An occluded coronary artery should be opened within 120 minutes or less to limit damage to the heart.

• Do not delay seeking help if you wake up with a burning pressing discomfort in the chest, feeling as if someone is sitting on your chest and associated with nausea, sweating, dizziness, weakness or discomfort in the arms, particularly without improving within minutes. Report and have an ECG done within 10 minutes.

• Most overweight persons have insulin resistance (no testing is necessary), rather start losing weight and exercise regularly.

• Everybody has heart arrhythmias at times, which is unlikely to be significant if this improves with activity, (only robots never have heart palpitations/arrhythmias).

• Tiredness is rarely of cardiac origin, but the inappropriate shortness of breath during activity should always be investigated.

• Do not ignore early morning headaches not associated with the previous night’s activities as these may indicate uncontrolled hypertension.

• The most important risk factor for vascular events is a family history of vascular disease before age 50 or 60 years.

• Smoking and hormone replacement medication carry a high risk for cerebral infarction, particularly in women.

• Smoking 20 cigarettes/day costs as much as a week’s holiday in Seychelles.

• Having a home blood-pressure monitor costs less than spending one night in hospital.

• You are not paying your doctor for the minutes or hours spent with you, but for the years of training and experience.

• The effect of years of bad lifestyle habits cannot be reversed within hours or days.


lmost 50 years ago, on 3rd December 1967, the world's first human to human heart transplant was performed by Dr Christiaan Barnard at

Groote Schuur Hospital. This was, and probably will remain, the most publicised medical event of all-time, headlining nearly every international newspaper, magazine and tabloid within days of the transplant. The idea of transplanting a heart from one human to another captured the minds and imaginations of the public like no other medical event before or since. The only other iconic event in that era which was equally well-publicised was man’s first landing on the moon 18 months later.

Brain-dead donor - an emotional debateThis first heart transplant placed Groote Schuur Hospital, the University of Cape Town and South Africa firmly on the international medical map. A heart transplant was seen by the public as transplanting the very soul of an individual from one person into another and provoked tremendous debate, some very emotional, around the ethics of transplantation and spurred on the International medical and philosophy community to develop the concept of brain death into law. Many countries around the world took many decades to adopt laws - most notably Japan, which took another thirty years (until 1997) to allow organ transplantation from brain dead donors. Japan’s first heart transplantation in 1968 led to the arrest of the surgeon who was charged with the murder of the donor, and similar incidents occurred around the world in the decade following the first transplant until brain death was more widely accepted. Even today many countries do not accept brain death, preventing organ transplantation as a therapeutic option.

Immunosuppression - the biggest challengeThis tremendous publicity generated by the first heart transplant occurred despite kidney and liver transplantation having preceded heart transplantation by many years. These prior surgical innovations were instrumental in paving the way for immu-nosuppression, vital for modifying the re-cipient immune response and preventing rejection from a genetically non-identical donor. The suppression of host-rejection as well as the prevention and treatment of subsequent side-effects remains the biggest challenge in organ transplantation.

Length and quality of life - the ultimate goalUltimately, the goal of a heart transplant is to improve both the length and quality of life and is indicated when medication and conventional cardiac surgery will not adequately alleviate symptoms of heart failure. As far as possible, transplant teams strive to help a recipient lead a life as simi-lar in quality to that of his or her peers, unconstrained by the limitations of heart failure. Although transplantation remains a successful procedure for the vast majority of patients, the ongoing care of heart trans-plant recipients is a challenge and requires intense follow-up by the transplant team and diligent compliance by the patient.

Technical variationsThe operation itself has changed very little since Dr Shumway from Stanford University in the USA, first described the technique in animals in the early 1960’s. Small technical variations, the use of heart preservation so-lutions, as well as the improvement in the heart-lung machine have optimised this procedure through the decades. The lack of donors has also been offset by the use of im-plantable assist devices (miniature mechan-ical pumps that help the heart) as a bridge to transplantation as well as the recent use

of donors whose hearts have stopped (do-nation after circulatory death, DCD), which would have been previously deemed un-suitable for transplantation. DCD donor hearts require resuscitative equipment and infrastructure that is not presently available in South Africa and long-term implantable assist devices are currently only accessible to patients with excellent health insurance.

Progress in post-operative care in the in-tensive care unit has made a significant improvement to early outcomes of heart transplantation, where patients without complications stay less than four days. In the last year, Groote Schuur hospital insti-tuted a long term extra-corporeal mem-brane oxygenation (ECMO) service, which brings the unit in-line with international standards for post-operative care in com-plicated cases. ECMO was also a pre-req-uisite for the re-commencement of a lung transplant programme and since mid-De-cember 2017 we have performed 3 double lung transplants. Once stabilised, patients are transferred to a general ward, where the post-transplant stay depends on the patient's general health and the function of the new heart. Age, general health, and response to the transplant all play a role in rehabilitation. However, most patients mobilise within a few days after surgery and are home within two weeks. Contin-ued, regular outpatient follow-up and re-habilitation is essential for a good outcome.

New drug innovationsApproximately 15 years after the first heart transplant, in the early 1980’s a “miracle” drug called Cyclosporine was discovered by Jean Borel, earning him a Nobel Prize. This drug was a significant breakthrough in the management of donor organ re-jection and transformed transplantation from an experimental operation in lead-ing academic medical centres to stand-ard medical treatment for end-stage organ failure with reproducible results which could be applied more widely. The numbers of all organ transplants rapidly escalated in the early 1980’s and reached a plateau a decade later when the avail-ability of donor organs became the major constraint. Cyclosporine is within the class of drugs called calcineurin inhibitors and

Heart transplantation

Prof Johan Brink, Cardiothoracic SurgeonDr Tim Pennel, Cardiothoracic SurgeonDr Karen Seele, Transplant Medical OfficerHeart Transplant Unit, Christiaan Barnard Division of Cardiothoracic Surgery University of Cape Town and Groote Schuur Hospital


the other commonly used drug within this class is Tacrolimus.

Calcineurin inhibitors are still the mainstay of treatment in organ transplantation, and its use has led to significantly fewer rejection episodes and a longer life expectancy. However, unwanted side-effects are a concern with this more effective immune suppression. Higher incidences of infection, hypertension, kidney damage and in some instances, long term kidney failure, diabetes, hyperlipidaemia and cancers are some of the side effects of immunosuppression. Some of the newer immunosuppressive drugs show promise of a reduction of some of these side effects, although these remain an ongoing challenge in the period immediately post-transplant, as well as in the long term.

Psychological wellbeingOver the years it became evident that psychological well-being is vital to successful outcomes in transplantation. In the first six months when steroid dosages are at their highest, feelings of anxiety, depression and in some extreme cases mania can develop. The importance of patient and family education as well as destigmatising these potential emotional problems is imperative. Carers have also learnt that patients who (for whatever reason), are unable to re-join work, have the potential to become despondent which may lead to depression. Those who are fortunate enough to return to work are sometimes regarded as chronically ill employees who take more time off work due to illness. Psychological and social support systems as well as treatment for depression need to be prioritised.

Major successes in the last 50 yearsFollowing the significant milestone 50 years ago, the Christiaan Barnard Division of Cardiothoracic Surgery at the University of Cape Town have transplanted 539 hearts and remains the only heart transplant facil-ity for state patients in South Africa, whilst also offering transplantation to private pa-tients at UCT Private Academic Hospital. Despite the challenges that exist with heart transplantation, the outcome has improved significantly over the past twenty years. The functional status of the recipient after the procedure is generally excellent, depending upon the individual’s motivation, with an anticipated survival of 85% at one year, de-creasing to 75% at five years.

The ongoing shortage of donor organs has fueled the search for alternative therapies for the failing heart. These therapies include mechanical artificial assist devices, which have been increasingly successful over the last few years - both as a bridge to heart transplantation and as so-called permanent destination therapy.

Assist devices and Xeno-transplantation The cost of these devices, with an initial outlay of over R2 million, and ongoing maintenance of a few hundred thousand Rand annually (and with the occasional need for replacement of the devices), places this outside the reach of the vast majority of South Africans. However, a few fortunate South Africans have had the financial resources available to pay for these devices in the private sector.

The holy grail of organ transplantation will remain the development of genetically engineered animals to provide organs compatible with the immune system of humans (xenotransplantation). Much research in this field has taken place over the last 20 to 30 years and although various immunological barriers have been overcome, and genetic breakthroughs

have been made to the point that organs from genetically discordant animal species have been successfully transplanted into primates, there is still a long way to go before xenotransplantation becomes a clinical reality for humans with organ failure.

International Commemoration (2-4 December 2017)The Christiaan Barnard Division of Cardiothoracic Surgery at the University of Cape Town, were proud hosts of an international celebration to commemorate the 50th anniversary of the world’s first heart transplant and to give thanks to the donor families from the 2nd to the 4th of December 2017 at Groote Schuur Hospital. We hope that the celebration of this courageous and innovative event will not only ensure the long-term treatment of heart failure patients but inspire young academics to follow in the legacy of Christiaan Barnard and his team five decades later.

This article was orginally published in Transplant News Vol 16 No 3 and is republished here with permission.

The Christiaan Barnard Division of Cardiothoracic Surgery at the University of Cape Town, were proud hosts of an international celebration to commemorate the 50th anniversary of the world’sfirst heart transplant and to give thanks to the donor families from the 2nd to the 4th of December 2017 at Groote Schuur Hospital.


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All this functionality is available at no cost on MPC.

Healthcare professionals can acquire CPD points with this newsletter by completing an online multiple-choice questionnaire on www.mpconsulting.co.za. All queries should be directed at [email protected] | 012 001 0452.

Register today on www.mpconsulting.co.za.

As a healthcare professional (HCP), you can effortlessly complete all your CPD compliance requirements on the SAMA accredited, Medical Practice Consulting (MPC) Online Education System, without having to leave the comfort of your own home or practice.

The MPC System provides a comprehensive CPD compliance solution that offers accredited CPD events, journals and courses, as well as industry leading CPD management services such as automatic issuing and secure storage of all your CPD certificates within the MPC CPD Manager.

What sets the MPC CPD Manager apart is its unique functionality that enables HCPs to elec-tronically submit your CPD activity records directly to the HPCSA at the click of the button when audited.

All this functionality is available at no cost on MPC.

Healthcare professionals can acquire CPD points with this newsletter by completing an online multiple-choice questionnaire on www.mpconsulting.co.za. All queries should be directed at [email protected] | 012 001 0452.

Register today on www.mpconsulting.co.za.

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LVEF-Left ventricular ejection fraction; ARBs - Angiotensin II receptor blockers

Zentiva South Africa (Pty) Ltd, a sanofi company. Reg no. 1931/002901/07. Sanofi House, 2 Bond Street, Grand Central Ext. 1 Midrand 1685. Tel: (011) 256 3700. Fax: (011) 256 3707. www.zentiva.com. SAZA.GCANW.17.03.0177 (05/17)

For full prescribing information, please refer to the package insert approved by the Medicines Regulatory Authority.

References: 1. Aterwin® (candesartan cilexetil) package insert. Zentiva South Africa (Pty) Ltd. 2. Zentiva a sanofi company webpage. 3. Seedat Y, Rayner B, Veriava Y. South African hypertension practice guideline 2014. Cardiovascular Journal of Africa. 2014;25(6):288-294. doi:10.5830/CVJA-2014-062. 4. Cernes R, Mashavi M, Zimlichman R. Differential clinical profile of candesartan compared to other angiotensin receptor blockers. Vasc Health Risk Manag. 2011;7:749-59. doi: 10.2147/VHRM.S22591. Epub 2011 Dec 12. 5. Zentiva Data on File. 14 March 2017.

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