Cardiovascular Disease in Pregnancy

Stephen Wasemiller, MD

10/22/2020

Disclosures

• None

Objectives

• To understand the presentations and treatments of commonly encountered cardiovascular issues during pregnancy

• To understand the risks and implications of maternal adult congenital heart disease during pregnancy

Outline

• Case

• Impact

• Physiology

• Congenital Disease

• Cardiovascular Complications

• Risk Assessment

• Counselling

Case

Case

• 21 year old female with history of systemic lupus erythematosus (SLE) with associated severe primary mitral regurgitation

• Multi-organ SLE involvement (cerebritis, nephritis, pericarditis)

• Primary mitral regurgitation by echo since 2015

Case

• Medications (July, 2018)• Plaquenil 200mg PO daily

• Prednisone 15mg PO daily

• CellCept 500mg PO BID

• Lisinopril 20mg daily

• Topical minoxidil QHS

• Gabapentin 100mg PO BID

• Norco 5/325

• Vitamin D3

• PPI

• Iron tablets

• Medical Hx• SLE with systemic involvement

(cerebritis, pleuritis, nephritis, pericarditis)

• Primary MR, TR, secondary to valvulitis

versus non-infectious endocarditis (Libman-Sacks)

• Fibromyalgia

• Raynaud’s phenomenon

• Depression

• Surgical history• None

• Family history• No family history of cardiovascular

disease or congenital heart defects

• Social history• No tobacco, EtOH, or drug use. Works

at a retail grocery store. Lives with her boyfriend.

Case

• TTE dated 2/2/2018: EF 65-70%, mild LV dilation, severe LA dilation with severe mitral regurgitation, MVA 4.1cm2, no mitral stenosis, moderate to severe tricuspid regurgitation

Case History

• Decision made to pursue surgery July of 2018

• Found out about pregnancy 3 days after visit with surgeon in July, 2018 (1st pregnancy)

• Was taken off CellCept, minoxidil, and lisinopril

• Established with ACHD/MFM

• Dyspneic throughout pregnancy

Case History

• Patient developed pre-eclampsia in late January, 2019. Was induced and ultimately delivered by C-section 1/25/19

• Tolerated delivery well with post-procedural tachycardia

• Received oral loop diuretic therapy and stress-dose steroids, discharged 1/30/19

Case History

• Readmitted 2/1/19-2/7/19 for pulmonary edema

• TEE obtained 2/5/19: LVEF 65% with posterior leaflet thickening, restriction, flail appearance

Impact of Cardiovascular Disease

Impact of Cardiovascular Disease

• Cardiovascular disease (CVD) affects 1-3% of pregnancies

• 16% of maternal mortality caused by cardiovascular disease

• Adult congenital heart disease (CHD) implicated in 2/3 of CVD deaths in pregnancy

• CHF, ischemia, arrhythmias

Nanna M, Stergiopoulos K. J Am Heart Assoc 2014

Maternal Mortality

Lancet 2016

Obstet Gynecol 2017

Impact of Cardiovascular Disease

• Maternal mortality is increasing in the US

• Increasing incidence in CVD

• Care needed to identify patients at risk and target therapy to reduce pregnancy-related cardiovascular issues

Physiologic Changes of Pregnancy

Physiologic Changes of Pregnancy

• Increase in cardiac output up to 50%

• Increased volume

• Increased HR (late)

• BP maintained due to decreased SVR

Physiologic Changes During Labor/Delivery

• Further increased CO leading up to delivery (25%)

• Initial increased in blood volume from uterine contraction

• IVC decompression

J Am Heart Assoc 2014

Physiologic Changes of Pregnancy

• Variations in physiology during pregnancy have profound effect on cardiovascular function• Systemic vasodilation can worsen symptoms with valvular stenosis

• Can improve symptoms in patient with regurgitant valvular lesions

• Exacerbate cyanotic heart conditions

• Risk stratification is essential in patients with known heart disease• ZAHARA

• Modified WHO Classification

• ROPAC

• CARPREG

Congenital Heart Disease in Pregnancy

Congenital Heart Disease

• 2 out of 3 patients with pregnancy-related cardiovascular complications are due to congenital heart defects

• Other CVD-implicated complications• Valvular disease 25%

• Cardiomyopathy 7%

• Ischemic heart disease 2%

• Increased survivability of CHD in the adult population has lead to increased incidence

Common CHD Defects

Acyanotic

• Ventricular Septal Defect (VSD)

• Atrial Septal Defect (ASD)

• Patent Ductus Arteriosis (PDA)

• Bicuspid Aortic Valve

• Coarctation of the Aorta

• AV Septal Defect

Cyanotic

• Transposition of the Great Arteries (TGA)

• Tetralogy of Fallot

• Tricuspid Atresia

• Pulmonary Atresia

• Total Anomalous Pulmonary Venous Return

• Single Ventricle Physiology

• (Connective tissue disorders such as Marfan’s)

Eisenmenger’s Syndrome

• Chronic left-to-right (high pressure to low pressure) shunting increasing pulmonary blood flow and leads to irreversible remodeling of pulmonary vasculature and pulmonary hypertension

• Leads to right-to-left shunting

• May develop from acyanotic congenital defects over time

• Mortality very high in pregnancy (20-50%)

• Elective termination should be discussed

Cardiovascular Complications

Peripartum Cardiomyopathy

• Incidence approximately 1 in 2000 pregnancies

• Etiology unclear

• Some associated characteristics• Advanced maternal age

• African American ethnicity

• Hypertension

• Multiparity

• Past history of peripartum cardiomyopathy

• LV recovery is possible in over 50% of patients

Peripartum Cardiomyopathy

• Treatment targeted toward guideline heart failure therapy, although therapy may need to be altered with breastfeeding/pregnancy• Diuretics

• Beta-blockers

• Vasodilators (ACE inhibitors/ARBs contraindicated with pregnancy)

• Aldosterone antagonists (contraindicated with pregnancy)

• Recovery less likely with LVEDD of >6cm or LVEF <35%

• Limited data on continuing therapy after LV recovery

• Lifelong follow-up

Hypertension

• Defined with absolute BP values SBP ≥ 140 or DBP ≥ 90

• HTN may be masked early in pregnancy due to early physiologic drop in BP

• Pre-existing HTN in 1-5%

• Medical therapy recommended for SBP ≥ 150 or DBP ≥ 95

• The earlier the onset of HTN in pregnancy, risk of recurrence higher

Pre-eclampsia

• New-onset hypertension with proteinuria occurring in second half of pregnancy

• More common in first pregnancy

• Affects 5-7% of pregnancies

• If pre-existing HTN present, risk of pre-eclampsia increases to 25%

• Symptoms• Headache

• Visual disturbance

• HELLP syndrome

• Edema

• Hyperreflexia

• Treatment: delivery of the fetus

Arrhythmias

• Atrial flutter/fibrillation• Relatively rare

• Can treat with rhythm control agents (limited data)

• Anticoagulation (LMWH) recommended prior to cardioversion

• TEE required if duration unknown or >48 hours

• Should remain on lifelong anticoagulation if risk profile (CHA2DS2-VASC) warrants it

• Rate control• Digoxin

• Metoprolol, propranolol

• Verapamil

• Dronedarone contraindicated

Arrhythmias

• SVT• Common, occurs 20-44% of pregnancies

• Responsive to adenosine or IV metoprolol

• Standing treatment with metoprolol, flecainide if symptomatic

• VT• Idiopathic RVOT most frequent type

• Acute treatment• Cardioversion if unstable and sustained VT

• Medical therapy with procainamide can be considered in stable cases

• Beta blockers usually effective in absence of structural heart disease

Acute Coronary Syndrome

• Relatively rare but on the rise• Occurs up to 6 out of 100,000 deliveries

• Risks• Hypertension

• Tobacco use

• Diabetes mellitus

• Family history

• Thrombophilia

• Severe post-partum hemorrhage

• Prompt diagnosis essential, maternal mortality 5-10%

• Referral to PCI center

Acute Coronary Syndrome

• Treatment• Heparin

• Beta blockers

• Aspirin

• Nitrates

• IIb/IIIa inhibitor therapy safety not clear • Peripartum bleed risk may preclude long-term treatment

• PCI treatment of choice• Bare metal stent versus drug-eluting stent

• Thrombolytic therapy if timely PCI not available

Spontaneous Coronary Artery Dissection (SCAD)

• Occurs proximately 1 in 16,000 pregnancies

• Up to one quarter of SCAD cases associated with pregnancy

• Can occur almost any time during pregnancy to several months post-partum

• Separation of the intima from the arterial wall

• Can lead to luminal disruption

Vijayaraghavan et al, Circulation 2014

Spontaneous Coronary Artery Dissection (SCAD)

• Treatment primarily supportive• ASA, beta blockers

• Unstable cases may require invasive revascularization• Risk of worsening dissection

• Majority of cases heal spontaneously over time

• Can recur in up to 18% of cases

Hypertrophic Cardiomyopathy

• Typically well tolerated• Mortality 0.5%

• Management mirrors general HCM management

• Beta-blockers should be continued, start if symptomatic

• Avoid hypovolemia• Use care with epidural anesthesia

Valvular Disease

• Complications caused by increase gradients across valves

• Murmurs are very common

• Important to determine normal from pathologic

• Pathology examples• Stenosis

• Rheumatic disease

• Congenital disease

• Radiation

• Degenerative (calcification)

• Regurgitation• Endocarditis

• Congenital

• Systemic illness (Carcinoid)

Mitral Stenosis

• Associated with rheumatic disease

• Severe mitral stenosis (MVA <1.5 cm2) • Mortality approaches 3% with pregnancy

• Can lead to intrauterine growth retardation

• Intervention should be done prior to pregnancy

• Percutaneous mitral commissurotomy should be considered in select patients after 20 weeks• High fetal risk of open heart surgery

Aortic Stenosis

• Mortality rare

• Bicuspid most common, then rheumatic

• Restriction of activity if HF occurs

• Diuretics for symptoms

• Pregnancy not advised for symptomatic severe AS or asymptomatic severe AS with reduced EF• Percutaneous valvuloplasty may be performed in select patients who

are symptomatic despite medical therapy

• Intervention recommended prior to pregnancy• Symptomatic (with exercise or at rest)

• LVEF <50%

Valvular Regurgitation

• Acute regurgitation lesions not well tolerated

• Heart failure commonly develops

• Severe MV/AV regurgitation should undergo repair prior to pregnancy

Prosthetic Valves

• Mechanical and bioprosthetic

• Advantages and disadvantages to both

• Mechanical• More durable

• Associated with lower event-free pregnancy (58%)

• Requires anticoagulation

• Bioprosthetic• Less durable, risk of deterioration and eventual reoperation higher

• Does not require anticoagulation

• Discussion regarding pregnancy planning essential if patient pregnant or planning to be come pregnant

Anticoagulation

• Indicated for mechanical valves, thromboembolism, atrial fibrillation, etc.

• Limited options• VKA (warfarin)

• LMWH

• Heparin

• VKA use in first trimester associated with increase risk of miscarriage and teratogenicity

• Management dependent on dose

Risk Assessment

ZAHARA

• Cardiac complications occurred in 7.6% of CHD patients during pregnancy

• Arrhythmias and heart failure most common cardiovascular complications in CHD patients

• Particular types of ACHD found to be associated with cardiac complications• Moderate or severe AV valvular regurgitation

• Presence of a mechanical prosthetic valve

• Cyanotic CHD (corrected or uncorrected)

• Use of cardiac medications prior to pregnancy

• Left heart obstruction

Drenthen W, et al. ZAHARA. Eur Heart J, 2010

CARPREG II

• Prospective study assessing maternal cardiovascular risk factors in pregnancy

• 1,938 women recruited 1994 through 2014• Congenital heart disease

• Acquired heart disease

• Arrhythmias

CARPREG II

• Adverse events occurred in 307 pregnancies (16%)

• Maternal death very rare, 11 cases (0.6%)

• Event occurrence• Antepartum 73%

• Labor and delivery 4%

• Postpartum 32%

Silversides CK, et al. CARPREG II Study. J Am Coll Cardiol, 2018

Silversides CK, et al. CARPREG II Study. J Am Coll Cardiol, 2018

CARPREG II

• From the CARPREG II study came predictors of adverse cardiovascular events• Past cardiac events/arrhythmias

• NYHA class III/IV or cyanosis

• Mechanical valve

• Ventricular dysfunction

• LVOT obstruction/left-sided valve disease (MS, AS)

• Pulmonary HTN

• CAD

• Aortopathy

• Late pregnancy assessment

• No prior cardiac intervention (for significant CAD)

CARPREG II

• Validated weighted scoring system for predicting maternal cardiac events with pregnancy

• Predicted risks for cardiac events• 0 – 1 point = 5%

• 2 points = 10%

• 3 points = 15%

• 4 points = 22%

• >4 points = 41%

Silversides CK, et al. CARPREG II Study. J Am Coll Cardiol, 2018

WHO Classification

• Classifies maternal risk by condition I-IVI - No detectable increase in mortality

II - Small increase in mortality, moderate increase in morbidity

III - Significant increase in mortality, severe increase in morbidity

IV - Extremely high mortality, pregnancy contraindicated

Regitz-Zagrosek V, et al. Eur Heart J, 2011

Roos-Hesselink J, et al. ROPAC. Eur Heart J, 2013

WHO Classification

• Higher classes associated with • Increased maternal mortality

• Increased hospital admissions

• Lower birthweight

• Higher risk of fetal demise

• Increased incidence of heart failure

• Increased likelihood of cesarian section

Stout, et al. Circulation 2019

Risk Classification Take-Aways

• Incorporates all information regarding maternal risk with regard to ACHD, structural heart disease, and acquired heart disease

• Should be incorporated in assessing all women with cardiovascular issues

• Maternal cardiac events are still relatively rare despite the increased relative risk of cardiovascular issues with pregnancy

• Early referral to multidisciplinary team (e.g. ACHD cardiologist, MFM physician, cardiac surgeon)

Summary

• CVD is on the rise leading to increases in maternal complications in pregnancy

• Pregnant adults with CHD require detailed risk assessment and close monitoring, typically at a large ACHD center with multidisciplinary support

• Different cardiovascular complications may occur during pregnancy making early recognition and diagnosis cornerstone of effective care

• Multiple risk assessment tools are available

Thank You

References

• Silversides CK, Grewal J, Mason J, Sermer M, Kiess M, Rychel V, Wald RM, Colman JM, Siu SC. Pregnancy Outcomes in Women With Heart Disease: The CARPREG II Study. J Am Coll Cardiol. 2018 May 29;71(21):2419-2430.

• Regitz-Zagrosek V, Roos-Hesselink JW, Bauersachs J, Blomström-Lundqvist C, Cífková R, De Bonis M, Iung B, Johnson MR, Kintscher U, Kranke P, Lang IM, Morais J, Pieper PG, Presbitero P, Price S, Rosano GMC, Seeland U, Simoncini T, Swan L, Warnes CA; ESC Scientific Document Group. 2018 ESC Guidelines for the management of cardiovascular diseases during pregnancy. Eur Heart J. 2018 Sep 7;39(34):3165-3241.

• Vijayaraghavan R, Verma S, Gupta N, Saw J. Pregnancy-related spontaneous coronary artery dissection. Circulation. 2014 Nov 18;130(21):1915-20.

• Hayward RM, Foster E, Tseng ZH. Maternal and Fetal Outcomes of Admission for Delivery in Women With Congenital Heart Disease. JAMA Cardiol. 2017 Jun 1;2(6):664-671.

• Stout KK, Daniels CJ, Aboulhosn JA, Bozkurt B, Broberg CS, Colman JM, Crumb SR, Dearani JA, Fuller S, Gurvitz M, KhairyP, Landzberg MJ, Saidi A, Valente AM, Van Hare GF. 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: Executive Summary: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Apr 2;139(14):e637-e697.

• Shaw D, Guise JM, Shah N, Gemzell-Danielsson K, Joseph KS, Levy B, Wong F, Woodd S, Main EK. Drivers of maternity care in high-income countries: can health systems support woman-centred care? Lancet. 2016 Nov 5;388(10057):2282-2295.

• Creanga AA, Syverson C, Seed K, Callaghan WM. Pregnancy-Related Mortality in the United States, 2011-2013. ObstetGynecol. 2017 Aug;130(2):366-373.

• Roos-Hesselink JW, Ruys TP, Stein JI, Thilén U, Webb GD, Niwa K, Kaemmerer H, Baumgartner H, Budts W, Maggioni AP, Tavazzi L, Taha N, Johnson MR, Hall R; ROPAC Investigators. Outcome of pregnancy in patients with structural or ischaemicheart disease: results of a registry of the European Society of Cardiology. Eur Heart J. 2013 Mar;34(9):657-65.