Pregnancy and Heart Failure TRP 2021

P R E G N A N C Y A N D H E A R T FA I L U R E

E V E R Y B O D Y ’ S M O S T F E A R E D T O P I C … .

W H AT K I N D O F Q U E S T I O N S T O E X P E C T ? ?

• “If I were a Royal College Examiner, what questions would I ask?”

• “What types of questions have been asked before?”

• “How might this year be different given the lack of an OSCE exam?”

L I S T 5 N O R M A L C A R D I O VA S C U L A R C H A N G E S I N P R E G N A N C Y

L I S T 5 N O R M A L C A R D I O VA S C U L A R C H A N G E S I N P R E G N A N C Y

• Systemic vasodilation resulting in a drop in SVR

• Increase in cardiac output

• Decreased blood pressure

• Increased heart rate

• Dilated cardiac chambers

L I S T 7 N O R M A L E C H O F I N D I N G S I N P R E G N A N C Y

L I S T 7 N O R M A L E C H O F I N D I N G S I N P R E G N A N C Y

• Dilated LV

• Dilated RV

• Dilated LA

• Dilated RA

• Increased LV mass

• Increased cardiac output

• Increased stroke volume

Increased aortic distensibility Trivial physiologic MR Trivial physiologic TR

6 N O R M A L C A R D I A C P H Y S I C A L E X A M F I N D I N G S I N P R E G N A N C Y

6 N O R M A L P H Y S I C A L E X A M F I N D I N G S I N P R E G N A N C Y

• Low-normal blood pressure

• Sinus tachycardia

• Systolic flow murmur

• Displaced Apex

• Elevated JVP

• S3

(Edema)

H E A R T FA I L U R E I N P R E G N A N C Y

• What kind of questions??

H E A R T FA I L U R E I N P R E G N A N C Y

• Pre-existing heart failure and pregnancy (ie DCM)

• Peri-partum cardiomyopathy

• Safety of heart failure medications in pregnancy

• Risk of recurrent peri-partum cardiomyopathy in those with a history thereof

• Counselling of risk (canmeds non medical expert roles still need to be tested even though no oral exam!!)

• Safety of cardiac tests in pregnancy

O T H E R P R E G N A N C Y I S S U E S N O T C O V E R E D H E R E :

• What to do with warfarin (ie mechanical heart valves)

• Congenital heart disease - contraindications to pregnancy

• Conditions with maternal mortality >50% (Read and study the modified WHO criteria)

• What valvular lesions or conditions are tolerated well in pregnancy

• Different choices in women of child bearing age (meds, valves) eg. statins

• Management of common cardiac conditions in pregnancy (pericarditis for example)

• SCAD

• Aortic aneurysm risk.

R E S O U R C E :

*There were no pregnancy related updates in 2021 guideline

P O T E N T I A L Q U E S T I O N S :

• List 5 classes of medications which are safe to use to treat HFrEF in a pregnant patient.

•

Numerous prespecified and post hoc analyses of theTOPCAT trial have been performed to guide the clinicalinterpretation and application of these data. Notably, 28.5%of participants were enrolled in the trial on the basis ofelevated NP levels. In this group, participants randomized tospironolactone had a 35% reduction in the primary end pointcompared with those who received placebo. This benefit ofspironolactone was not observed among patients who enteredthe trial on the basis of a previous HF hospitalization. Markeddifferences in baseline demographic characteristics wereobserved between inclusion criteria groups; those enrolled onthe basis of elevated NP levels were older, had worse renalfunction at baseline (higher serum creatinine and lowereGFR), and were less likely to be recruited at centres in Russiaor Georgia. A significant proportion of patients recruited inthe latter region might not have received the assigned studytreatment and thus reliable results from TOPCAT mightcome mainly from the Americas.175 The observed geographicvariation analysis showed a 15% RRR in the primary endpoint favouring spironolactone in patients enrolled in theAmericas vs those enrolled in Russia or Georgia.86

7.1.2.3. b-Blockers in HFpEF

Although b-blockers provide a plausible physiologicalmechanism of action for improved outcomes by prolongationof diastolic filling time, reduction of myocardial ischemia,control of hypertension, and arrhythmia prophylaxis, theavailable quality of evidence and heterogeneity of findingsfrom meta-analyses precludes a firm recommendation for useof this medication class in HFpEF at this time.176-179 As anexample, an LVEF subgroup analysis of the Study of theEffects of Nebivolol Intervention on Outcomes and Reho-spitalization in Seniors With Heart Failure (SENIORS)trial180 showed a 19% reduction in the combined primary endpoint of all-cause mortality and cardiovascular hospitalization(HR, 0.81; 95% CI, 0.63-1.04; P for subgroup interaction ¼0.043) among study participants with an LVEF " 35% whoreceived nebivolol compared with placebo. However, becauseof the small effect size of nebivolol in the main SENIORStrial, this analysis lacks power to definitively rule out a sig-nificant interaction between outcomes of interest and EF.

High dropout rates in the main trial, small sample size, andlow event rate in the nonreduced EF group raise furtherquestions about the reproducibility of these findings.

7.1.2.4. Nitrates in HFpEF

Nitrates have been broadly used in patients with establishedCVD, however, the role of long-acting nitrates in patients withHFpEF is unclear. TheNitrate’s Effect on ActivityTolerance inHeart Failure With Preserved Ejection Fraction (NEAT-HFpEF) trial181 enrolled 110 patients to a long-acting nitrate(isosorbide mononitrate 120 mg/d) or placebo into a 6-weekcrossover trial to test the efficacy and safety of this approach.There was no beneficial effect of nitrates seen in this groupon biomarkers, exercise tolerance, activity level, or clinicaleventsdand there was a nonsignificant trend toward a lower rateof daily activity for patients who received long-acting nitrates.

Practical tip. Excessive diuretic use can lead to decreasedcardiac output and compromise of renal function. Everyattempt should be made to use the lowest possible dose ofdiuretic to achieve and maintain euvolemia.

Practical tip. There is insufficient quality of data to pro-vide strong recommendations regarding statin therapy inHFpEF, so the decision to treat should be customized and onthe basis of existing guidelines for primary and secondaryprevention of CVD.

Practical tip. After an MRA or ARB is initiated and with achange in dose, serum potassium and creatinine should be

Table 35. Medications that might be useful for pregnant women withHF

Medication Use in pregnancy*

b-Blockers Should be continued or initiated during pregnancyRequires close fetal monitoring for growth retardationВ-1 selective antagonists preferred to avoid potential

increased uterine tone and decreased uterine perfusionDigoxin May be used if volume overload symptoms persist despite

vasodilator and diuretic therapyDiuretics May be used, but with caution regarding excessive volume

contraction leading to reduced placental perfusionHydralazine May be used for management of HF symptoms or elevated

blood pressureNitrates May be used to treat decompensated HF pregnancy

HF, heart failure.* Avoid all renin-angiotensin-aldosterone system inhibitors (angiotensin-

converting enzyme inhibitors, angiotensin receptor blockers, mineralocorti-coid receptor antagonists, angiotensin receptor neprilysin inhibitors, renininhibitors).

RECOMMENDATION

46. We suggest candesartan be considered to reduce HFhospitalizations in patients with HFpEF (WeakRecommendation; Moderate-Quality Evidence).

47. We recommend systolic/diastolic hypertension becontrolled according to current Canadian Hyperten-sion Education Program hypertension guidelines(2017) (http://www.onlinecjc.ca/article/S0828-282X(17)30110-1/abstract) to prevent and treat HFpEF(Strong Recommendation; High-Quality Evidence).

48. We recommend loop diuretics be used to controlsymptoms of congestion and peripheral edema (StrongRecommendation; Moderate-Quality Evidence).

49. We suggest that in individuals with HFpEF, serum po-tassium< 5.0 mmol/L, and an eGFR> 30mL/min, anMRA like spironolactone should be considered, withclose surveillance of serum potassium and creatinine(Weak Recommendation;Moderate-Quality Evidence).

Values and preferences. These recommendations placea high value on the known etiologic factors for HFpEFand less on known outcome-modifying treatments which,unlike in HFrEF, are still limited.

The MRA recommendation is on the basis of post hocgeographic subgroup analyses of the TOPCAT trial con-ducted within North and South America mentionedpreviously.

Ezekowitz et al. 13752017 CCS HF Guidelines Update

Metoprolol OK Avoid Atenolol

VA R I AT I O N S :

• Heart failure medications NOT safe in pregnancy

• Renal anomalies with ACE/ARB/ARNI

• SGLT-2 renal anomalies in animals

• A patient with DCM (FC I, EF >30, well compensated etc) on the following medications wants to conceive. What are you going to do? (stop the bad stuff, put her on the OK stuff, counsel her about risks etc)

P E R I PA R T U M C A R D I O M Y O PAT H Y

• What kind of questions do you think the RC might ask?

D E F I N I T I O N O F P P C M ( 3 )

• Development of heart failure with EF <45% within 1 month of delivery or 5 months post partum. No obvious other cause of LV dysfunction.

L I S T S I X R I S K FA C T O R S F O R T H E D E V E L O P M E N T O F P P C M ( 6 )

• Multiparity

• Multiple fetal gestation

• Advanced maternal age

• Family history

• Diabetes

• HTN

Preeclampsia Smoking Ethnicity

Prolonged tocolytic therapy

P R O G N O S I S A N D R I S K O F R E C U R R E N C E

• EF returns to normal in 23 - 72% of patients (almost exclusively in first 6 months)

• Risk of recurrence about 1/3 in those whose EF has returned to normal

• Women should be advised against future pregnancy if EF does not return to normal.

7.5.3.1. Diagnosis and management

Hemodynamic changes in normal pregnancy can precipi-tate HF in patients who are susceptible or have another un-derlying etiology (Table 33). Decompensation can occur atany time; however it is more common in the late stages ofpregnancy and peripartum. Physical examination for HF-related physical signs can be challenging in pregnancy. It isimportant for clinicians to recognize cardiovascular symptomsand signs that are not normally present in pregnancy(Table 34). Echocardiography remains the preferred imagingmodality for HF during pregnancy. Women with AHF duringpregnancy should be managed according to the guidelines forAHF and should be referred to a tertiary care centre withexpertise in advanced HF management, including MCS andcardiac transplantation.515,516

7.5.3.2. Medical therapy of HF in pregnancy

HF in pregnancy should be treated according to theCCS HF guidelines for acute and chronic HF. However,many standard therapies of HF are considered fetotoxic andshould not be used during pregnancy including ACEis,ARBs, and MRAs.517,518 There are no data on the use ofARNIs and thus they are not recommended during preg-nancy. When b blockade is used, b1-selective drugs (eg,metoprolol) should be preferred. Atenolol should not beused.519 Diuretics can be used if pulmonary congestion ispresent. Medications that might be used for pregnantwomen with HF are shown in Table 35. An additionalcomprehensive list of medications is available at www.motherrisk.org.515,516

7.5.3.3. PPCM

PPCM is a diagnosis of exclusion typically defined as HFwith an LVEF of < 45% within 1 month before delivery to 5months postpartum. Pathophysiologic mechanisms are notclearly defined but might include genetic predisposition,520

oxidative stress, and immune mechanisms,521,522 as well asviral infections521 and prolactin.523 Risk factors for the de-velopments of PPCM include multiparity and multiple fetalgestation, advanced maternal age, family history, ethnicity,hypertension, preeclampsia, smoking, diabetes, and prolongedtocolytic therapy.524

In addition to standard diagnostic tests for HF and preg-nancy, there is now data to support the use of biomarkers fordiagnosis as well as prognosis in PPCM.525,526 There havebeen several case reports and a small RCT to evaluatebromocriptine527 with inconclusive results and uncertainsafety.528-530

Despite advances in HF treatment mortality as well asmorbidity related to PPCM remains high. In case series, LVsystolic function returns to normal in 23%-72% ofpatients.524,531-533 Less is known about the risk of subsequentpregnancy; however, the 2 largest studies of PPCM suggestrelapse occurs in almost one-third of the cases.534,535 Thusmost would agree that individualized counselling should occurin individuals with PPCM and they should be advised againstfuture pregnancy particularly if recovery of LVEF has notoccurred.524,536

Practical tip. Vaginal delivery is preferred in women withstable cardiac conditions.

RECOMMENDATION

142. We recommend that pregnant women (or those inthe peripartum period) with AHF should bemanaged according to the CCS guidelines for AHFand should be referred to a tertiary centre withexpertise in advanced HF management, includingMCS and cardiac transplantation (Strong Recom-mendation; Low-Quality Evidence).

143. We recommend that NPs be used for diagnostic andprognostic purposes in peripartum cardiomyopathy(PPCM) (Strong Recommendation; Low-QualityEvidence).

144. We recommend that bromocriptine not be usedroutinely for PPCM (Strong Recommendation;Low-Quality Evidence).

Values and preferences. Adequately powered andappropriately designed RCTs have not been completed.The safety of bromocriptine is not well established.

145. We recommend that echocardiography be performedin women with worsening or suspected new-onsetHF during pregnancy (Strong Recommendation;Low-Quality Evidence).

146. We recommend prepregnancy counselling in allwomen with a known history of HF or PPCM(Strong Recommendation; Low-Quality Evidence).

147. We recommend preconception genetic counsellingin women with inheritable cardiac diseases that canaffect cardiac function, including inheritable car-diomyopathies (Strong Recommendation; Low-Quality Evidence).

148. We recommend maternal risk assessment and fre-quency of expert follow-up should be determinedusing the modified WHO risk classification (StrongRecommendation; Low-Quality Evidence).

149. We recommend that decisions regarding timing andmode of delivery should be on the basis of obstetricalfactors (StrongRecommendation; Low-Quality Evidence).

Values and preferences. Cesarean deliveries are notroutinely necessary and might additional risk to patientswith HF. Delivery before term for cardiac decompensationis rarely required.

RECOMMENDATION

150. We recommend that patients with PPCM who donot recover normal LV function should be advisedagainst future pregnancies because of the high risk ofworsening HF and death (Strong Recommendation;Moderate-Quality Evidence).

151. We recommend that patients with PPCM whorecover normal LV function should be advisedregarding the potential for recurrent LV dysfunctionin subsequent pregnancies (Strong Recommenda-tion; Moderate-Quality Evidence).

Ezekowitz et al. 14072017 CCS HF Guidelines Update

R E C O M M E N D AT I O N S F O R M O N I T O R I N G A N D A R O U N D D E L I V E R Y

R E C O M M E N D AT I O N S F O R M O N I T O R I N G A N D A R O U N D D E L I V E R Y

• Should be followed by cardiologist/heart function clinic in a tertiary care centre with access to mechanical support/transplant if possible (and co-managed by high risk obstetrics/MFM)

• Echocardiography and BNP for monitoring (new symptoms, change in chronic symptoms)

• Bromocriptine not recommended CCS 2017 (not enough evidence). Is recommended as ‘may be considered’ ESC 2018.

• Vaginal delivery is preferred in women with stable heart conditions.

D I S C U S S I O N

• Management of SCAD in pregnancy

• Antiarrhythmics safety in pregnancy

• Genetic counselling for patients with inherited heart disease wanting to conceive

M AY 2 0 2 0

June 9, 2020 Circulation. 2020;141:e884–e903. DOI: 10.1161/CIR.0000000000000772e884

Laxmi S. Mehta, MD, FAHA, Chair

Carole A. Warnes, MD, FAHA, Vice Chair

Elisa Bradley, MDTina Burton, MDKatherine Economy, MDRoxana Mehran, MDBasmah Safdar, MDGarima Sharma, MDMalissa Wood, MDAnne Marie Valente, MDAnnabelle Santos Volgman,

MD, FAHAOn behalf of the American

Heart Association Council on Clinical Cardiology; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular and Stroke Nursing; and Stroke Council

© 2020 American Heart Association, Inc.

AHA SCIENTIFIC STATEMENT

Cardiovascular Considerations in Caring for Pregnant PatientsA Scientific Statement From the American Heart Association

Circulation

https://www.ahajournals.org/journal/circ

ABSTRACT: Cardio-obstetrics has emerged as an important multidisciplinary field that requires a team approach to the management of cardiovascular disease during pregnancy. Cardiac conditions during pregnancy include hypertensive disorders, hypercholesterolemia, myocardial infarction, cardiomyopathies, arrhythmias, valvular disease, thromboembolic disease, aortic disease, and cerebrovascular diseases. Cardiovascular disease is the primary cause of pregnancy-related mortality in the United States. Advancing maternal age and preexisting comorbid conditions have contributed to the increased rates of maternal mortality. Preconception counseling by the multidisciplinary cardio-obstetrics team is essential for women with preexistent cardiac conditions or history of preeclampsia. Early involvement of the cardio-obstetrics team is critical to prevent maternal morbidity and mortality during the length of the pregnancy and 1 year postpartum. A general understanding of cardiovascular disease during pregnancy should be a core knowledge area for all cardiovascular and primary care clinicians. This scientific statement provides an overview of the diagnosis and management of cardiovascular disease during pregnancy.

Key Words: AHA Scientific Statements ◼ cardiovascular disease ◼ maternal mortality ◼ obstetrics ◼ pregnancy

Cardiovascular disease (CVD) is the leading cause of pregnancy-related mortal-ity in the United States and has gradually increased over time (from 7.2 to 17.2 deaths per 100 000 live births from 1987–2015).1 The rise in maternal

mortality has been attributed to increasing numbers of women at advanced mater-nal age undertaking pregnancy, comorbid preexisting conditions such as diabetes mellitus and hypertension, and the growing number of women with congenital heart disease surviving to childbearing age.1,2 Racial and ethnic disparities in preg-nancy-related mortality are significant, peaking among black non-Hispanic women followed by American Indian/Alaskan Native non-Hispanic women, Asian/Pacific Islander non-Hispanic women, white non-Hispanic women, and Hispanic women (42.8, 32.5, 14.2, 13.0, and 11.4 deaths per 100 000 live births, respectively).1

Early and specialized multidisciplinary care in the antepartum, peripartum, and postpartum time frames is essential to improve cardiovascular outcomes and to reduce maternal mortality up to the first year postpartum (Figure 1). The cardio-obstetrics team (also referred to as the pregnancy heart team)3,4 should provide a compre-hensive review of maternal cardiovascular risk, obstetric risk, and fetal risk and outcomes. This includes expectant management and prepregnancy counseling on cardiac medication safety throughout pregnancy and lactation phases. The cardio-obstetrics team is often made up of obstetricians, cardiologists, anesthesiologists,

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M O D I F I E D W H O C R I T E R I A

appears valuable to predict maternal risk, although overestimationcan occur.57,73 The CARPREG risk score is described in Table 4 . Inwomen with congenital heart disease, the CARPREG score12 mayalso be associated with a higher risk of late cardiovascular events post-pregnancy.74 The predictors from the ZAHARA study57 (Table 5 )have not yet been validated in other studies. It should be noted thatpredictors and risk scores from the CARPREG and ZAHARAstudies are highly population dependent. Important risk factorsincluding pulmonary arterial hypertension (PAH) and dilated aortawere not identified because they were under-represented in thesestudies. The CARPREG study included acquired and congenitalheart disease, while the ZAHARA study investigated a populationwith congenital heart disease only.

The Task Force recommends that maternal risk assessment iscarried out according to the modified World Health Organization(WHO) risk classification.72 This risk classification integrates allknown maternal cardiovascular risk factors including the underlyingheart disease and any other co-morbidity. It includes contraindica-tions for pregnancy that are not incorporated in the CARPREGand ZAHARA risk scores/predictors. The general principles ofthis classification are depicted in Table 6 . A practical applicationis given in Table 7 . In women in WHO class I, risk is very low,and cardiology follow-up during pregnancy may be limited toone or two visits. Those in WHO II are at low or moderate risk,and follow-up every trimester is recommended. For women inWHO class III, there is a high risk of complications, and frequent(monthly or bimonthly) cardiology and obstetric review duringpregnancy is recommended. Women in WHO class IV should beadvised against pregnancy but, if they become pregnant and willnot consider termination, monthly or bimonthly review is needed.

Neonatal complications occur in 20–28% of patients with heartdisease12,56,57,75,76 with a neonatal mortality between 1% and4%.12,56,57 Maternal and neonatal events are highly correlated.57

Predictors of neonatal complications are listed in Table 8 .

Table 7 Modified WHO classification of maternalcardiovascular risk: application

Conditions in which pregnancy risk is WHO I

� Uncomplicated, small or mild - pulmonary stenosis - patent ductus arteriosus - mitral valve prolapse

� Successfully repaired simple lesions (atrial or ventricular septal defect, patent ductus arteriosus, anomalous pulmonary venous drainage).

� Atrial or ventricular ectopic beats, isolated

Conditions in which pregnancy risk is WHO II or III

WHO II (if otherwise well and uncomplicated)

� Unoperated atrial or ventricular septal defect

� Repaired tetralogy of Fallot

� Most arrhythmias

WHO II–III (depending on individual)

� Mild left ventricular impairment

� Hypertrophic cardiomyopathy

� Native or tissue valvular heart disease not considered WHO I or IV

� Marfan syndrome without aortic dilatation� Aorta <45 mm in aortic disease associated with bicuspid aortic valve

� Repaired coarctation

WHO III

� Mechanical valve

� Systemic right ventricle

� Fontan circulation

� Cyanotic heart disease (unrepaired)

� Other complex congenital heart disease

� Aortic dilatation 40� 45 mm in Marfan syndrome� Aortic dilatation 45� 50 mm in aortic disease associated with bicuspid aortic valve

Conditions in which pregnancy risk is WHO IV (pregnancy contraindicated)

� Pulmonary arterial hypertension of any cause

� Severe systemic ventricular dysfunction (LVEF <30%, NYHA III� IV)

� Previous peripartum cardiomyopathy with any residual impairment of left ventricular function

� Severe mitral stenosis, severe symptomatic aortic stenosis

� Marfan syndrome with aorta dilated >45 mm� Aortic dilatation >50 mm in aortic disease associated with bicuspid aortic valve

� Native severe coarctation

Adapted from Thorne et al.73

LVEF ¼ left ventricular ejection fraction; NYHA ¼ New York Heart Association;WHO ¼World Health Organization.

Table 6 Modified WHO classification of maternalcardiovascular risk: principles

Risk class Risk of pregnancy by medical condition

INo detectable increased risk of maternal mortality and no/mild increase in morbidity.

IISmall increased risk of maternal mortality or moderate increase in morbidity.

III

Signi� cantly increased risk of maternal mortality or severe morbidity. Expert counselling required. If pregnancy is decided upon, intensive specialist cardiac and obstetric monitoring needed throughout pregnancy, childbirth, and the puerperium.

IV

Extremely high risk of maternal mortality or severe morbidity; pregnancy contraindicated. If pregnancy occurs termination should be discussed. If pregnancy continues, care as for class III.

Modified from Thorne et al.72

WHO ¼World Health Organization

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P R E G N A N C Y C O N T R A I N D I C AT E D

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Pregnancy and Heart Failure TRP 2021

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