Heart Failure Subtypes and Cardiomyopathies in Women.

Heart failure affects over 2.6 million women and 3.4 million men in the United States with known sex differences in epidemiology, management, response to treatment, and outcomes across a wide spectrum of cardiomyopathies that include peripartum cardiomyopathy, hypertrophic cardiomyopathy, stress cardiomyopathy, cardiac amyloidosis, and sarcoidosis. Some of these sex-specific considerations are driven by the cellular effects of sex hormones on the renin-angiotensin-aldosterone system, endothelial response to injury, vascular aging, and left ventricular remodeling. Other sex differences are perpetuated by implicit bias leading to undertreatment and underrepresentation in clinical trials. The goal of this narrative review is to comprehensively examine the existing literature over the last decade regarding sex differences in various heart failure syndromes from pathophysiological insights to clinical practice.

An Updated Review on the Role of Non-dihydropyridine Calcium Channel Blockers and Beta-blockers in Atrial Fibrillation and Acute Decompensated Heart Failure: Evidence and Gaps.

PURPOSE: The 2021 European Society of Cardiology guidelines on acute and chronic heart failure (HF) recommend that non-dihydropyridine calcium channel blockers (NDCC) should be avoided in patients with HF with reduced ejection fraction. It also emphasizes that beta-blockers only be initiated in clinically stable, euvolemic patients. Despite these recommendations, NDCC and beta-blockers are often still employed in patients with AF with rapid ventricular response and acute decompensated HF. The relative safety and efficacy of these therapies in this setting is unclear. METHODS: To address the question of the safety and efficacy of NDCC and beta-blockers for acute rate control in decompensated HF, we provide a perspective on the literature of NDCC and beta-blockers in chronic HF with reduced and preserved ejection fraction and AF, including trials on the management of AF with rapid ventricular response with and without HF. RESULTS: Robust data demonstrates mortality benefits when beta-blockers are used in patients with chronic HF with reduced ejection fraction. The data that inform the contraindication of NDCC in HF with reduced ejection fraction are outdated and were not primarily designed to address the efficacy and safety of rate control of AF in patients with HF. Several studies indicate that for acute rate control, NDCC and beta-blockers are both efficacious therapies, especially in the setting of tachycardia-induced cardiomyopathy. CONCLUSION: Future studies are needed to assess the safety and efficacy of beta-blockers and NDCC in both acute and chronic AF with HF with reduced and preserved ejection fraction.

Hypertensive disorders of pregnant women with heart disease: the ESC EORP ROPAC Registry.

AIMS: Hypertensive disorders of pregnancy (HDP) occur in 10% of pregnancies in the general population, pre-eclampsia specifically in 3-5%. Hypertensive disorders of pregnancy may have a high prevalence in, and be poorly tolerated by, women with heart disease. METHODS AND RESULTS: The prevalence and outcomes of HDP (chronic hypertension, gestational hypertension or pre-eclampsia) were assessed in the ESC EORP ROPAC (n = 5739), a worldwide prospective registry of pregnancies in women with heart disease.The overall prevalence of HDP was 10.3%, made up of chronic hypertension (5.9%), gestational hypertension (1.3%), and pre-eclampsia (3%), with significant differences between the types of underlying heart disease (P < 0.05). Pre-eclampsia rates were highest in women with pulmonary arterial hypertension (PAH) (11.1%), cardiomyopathy (CMP) (7.1%), and ischaemic heart disease (IHD) (6.3%). Maternal mortality was 1.4 and 0.6% in women with vs. without HDP (P = 0.04), and even 3.5% in those with pre-eclampsia. All pre-eclampsia-related deaths were post-partum and 50% were due to heart failure. Heart failure occurred in 18.5 vs. 10.6% of women with vs. without HDP (P < 0.001) and in 29.1% of those with pre-eclampsia. Perinatal mortality was 3.1 vs. 1.7% in women with vs. without HDP (P = 0.019) and 4.7% in those with pre-eclampsia. CONCLUSION: Hypertensive disorders of pregnancy and pre-eclampsia rates were higher in women with CMP, IHD, and PAH than in the general population. Adverse outcomes were increased in women with HDP, and maternal mortality was strikingly high in women with pre-eclampsia. The combination of HDP and heart disease should prompt close surveillance in a multidisciplinary context and the diagnosis of pre-eclampsia requires hospital admission and continued monitoring during the post-partum period.

Genetic and Phenotypic Landscape of Peripartum Cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) occurs in ≈1:2000 deliveries in the United States and worldwide. The genetic underpinnings of PPCM remain poorly defined. Approximately 10% of women with PPCM harbor truncating variants in TTN (TTNtvs). Whether mutations in other genes can predispose to PPCM is not known. It is also not known if the presence of TTNtvs predicts clinical presentation or outcomes. Nor is it known if the prevalence of TTNtvs differs in women with PPCM and preeclampsia, the strongest risk factor for PPCM. METHODS: Women with PPCM were retrospectively identified from several US and international academic centers, and clinical information and DNA samples were acquired. Next-generation sequencing was performed on 67 genes, including TTN, and evaluated for burden of truncating and missense variants. The impact of TTNtvs on the severity of clinical presentation, and on clinical outcomes, was evaluated. RESULTS: Four hundred sixty-nine women met inclusion criteria. Of the women with PPCM, 10.4% bore TTNtvs (odds ratio=9.4 compared with 1.2% in the reference population; Bonferroni-corrected P [P*]=1.2×10-46). We additionally identified overrepresentation of truncating variants in FLNC (odds ratio=24.8, P*=7.0×10-8), DSP (odds ratio=14.9, P*=1.0×10-8), and BAG3 (odds ratio=53.1, P*=0.02), genes not previously associated with PPCM. This profile is highly similar to that found in nonischemic dilated cardiomyopathy. Women with TTNtvs had lower left ventricular ejection fraction on presentation than did women without TTNtvs (23.5% versus 29%, P=2.5×10-4), but did not differ significantly in timing of presentation after delivery, in prevalence of preeclampsia, or in rates of clinical recovery. CONCLUSIONS: This study provides the first extensive genetic and phenotypic landscape of PPCM and demonstrates that predisposition to heart failure is an important risk factor for PPCM. The work reveals a degree of genetic similarity between PPCM and dilated cardiomyopathy, suggesting that gene-specific therapeutic approaches being developed for dilated cardiomyopathy may also apply to PPCM, and that approaches to genetic testing in PPCM should mirror those taken in dilated cardiomyopathy. Last, the clarification of genotype/phenotype associations has important implications for genetic counseling.

Society for Maternal-Fetal Medicine Consult Series #61: Anticoagulation in pregnant patients with cardiac disease.

Pregnancy in individuals with a mechanical heart valve has been classified as very high risk because of a substantially increased risk of maternal mortality or severe morbidity. Lifelong therapeutic anticoagulation is a principal component of the medical management of mechanical heart valves to prevent valve thrombosis. Anticoagulation regimens indicated outside of pregnancy for patients with mechanical valves should be continued during pregnancy with the possibility of modifications based on the type of valve, the trimester of pregnancy, individual risk tolerance, and circumstances around the time of delivery. The purpose of this document is to provide recommendations regarding the management of anticoagulation for common cardiac conditions complicating pregnancy, including mechanical heart valves, atrial fibrillation, systolic heart failure, and congenital heart disease.

Cardiovascular effects of preeclampsia.

PURPOSE OF REVIEW: Preeclampsia complicates 3-5% of first and 15% of subsequent pregnancies. This study reviews the evidence of increase cardiovascular risk in these women. RECENT FINDINGS: Women with preeclampsia are at two-fold higher risk for development of coronary artery disease, stroke and death, and four-fold increased risk of heart failure. Preeclampsia developed in early part of pregnancy confers greater risk than later in pregnancy. Common factors that predispose women to preeclampsia also confer high risk for developing cardiovascular disease include obesity, metabolic abnormalities, dyslipidaemia, insulin resistance, heightened inflammatory responses, hypercoagulable states and endothelia dysfunction. SUMMARY: Patients with preeclampsia should be screened at regular intervals by a preventive cardiologist and treated accordingly.

Pregnancy outcomes in women with cardiovascular disease: evolving trends over 10 years in the ESC Registry Of Pregnancy And Cardiac disease (ROPAC).

AIMS: Reducing maternal mortality is a World Health Organization (WHO) global health goal. Although maternal deaths due to haemorrhage and infection are declining, those related to heart disease are increasing and are now the most important cause in western countries. The aim is to define contemporary diagnosis-specific outcomes in pregnant women with heart disease. METHODS AND RESULTS: From 2007 to 2018, pregnant women with heart disease were prospectively enrolled in the Registry Of Pregnancy And Cardiac disease (ROPAC). Primary outcome was maternal mortality or heart failure, secondary outcomes were other cardiac, obstetric, and foetal complications. We enrolled 5739 pregnancies; the mean age was 29.5. Prevalent diagnoses were congenital (57%) and valvular heart disease (29%). Mortality (overall 0.6%) was highest in the pulmonary arterial hypertension (PAH) group (9%). Heart failure occurred in 11%, arrhythmias in 2%. Delivery was by Caesarean section in 44%. Obstetric and foetal complications occurred in 17% and 21%, respectively. The number of high-risk pregnancies (mWHO Class IV) increased from 0.7% in 2007-2010 to 10.9% in 2015-2018. Determinants for maternal complications were pre-pregnancy heart failure or New York Heart Association >II, systemic ejection fraction <40%, mWHO Class 4, and anticoagulants use. After an increase from 2007 to 2009, complication rates fell from 13.2% in 2010 to 9.3% in 2017. CONCLUSION: Rates of maternal mortality or heart failure were high in women with heart disease. However, from 2010, these rates declined despite the inclusion of more high-risk pregnancies. Highest complication rates occurred in women with PAH.

Shared Genetic Predisposition in Peripartum and Dilated Cardiomyopathies.

Background Peripartum cardiomyopathy shares some clinical features with idiopathic dilated cardiomyopathy, a disorder caused by mutations in more than 40 genes, including TTN, which encodes the sarcomere protein titin. Methods In 172 women with peripartum cardiomyopathy, we sequenced 43 genes with variants that have been associated with dilated cardiomyopathy. We compared the prevalence of different variant types (nonsense, frameshift, and splicing) in these women with the prevalence of such variants in persons with dilated cardiomyopathy and with population controls. Results We identified 26 distinct, rare truncating variants in eight genes among women with peripartum cardiomyopathy. The prevalence of truncating variants (26 in 172 [15%]) was significantly higher than that in a reference population of 60,706 persons (4.7%, P=1.3×10(-7)) but was similar to that in a cohort of patients with dilated cardiomyopathy (55 of 332 patients [17%], P=0.81). Two thirds of identified truncating variants were in TTN, as seen in 10% of the patients and in 1.4% of the reference population (P=2.7×10(-10)); almost all TTN variants were located in the titin A-band. Seven of the TTN truncating variants were previously reported in patients with idiopathic dilated cardiomyopathy. In a clinically well-characterized cohort of 83 women with peripartum cardiomyopathy, the presence of TTN truncating variants was significantly correlated with a lower ejection fraction at 1-year follow-up (P=0.005). Conclusions The distribution of truncating variants in a large series of women with peripartum cardiomyopathy was remarkably similar to that found in patients with idiopathic dilated cardiomyopathy. TTN truncating variants were the most prevalent genetic predisposition in each disorder.

Peripartum cardiomyopathy: approach to management.

PURPOSE OF REVIEW: To provide recommendations for the diagnosis and management of patients with peripartum cardiomyopathy (PPCM). RECENT FINDINGS: PPCM is pregnancy-associated myocardial disease that occurs during pregnancy or postpartum and is characterized by the development of heart failure due to marked left ventricular (LV) systolic dysfunction. The disease is relatively uncommon, but its incidence is increasing, and it remains an important cause of cardiac-related maternal morbidity and mortality in previously healthy young women. With early diagnosis and treatment, the majority of the patients demonstrate recovery. SUMMARY: The review provides information on the clinical presentation, prognosis and contemporary management of PPCM as well as the approach to subsequent pregnancies, labor and delivery and long-term psychological consequences of the disease.

Peripartum Cardiomyopathy.

Peripartum cardiomyopathy is a potentially life-threatening pregnancy-associated disease that typically arises in the peripartum period and is marked by left ventricular dysfunction and heart failure. The disease is relatively uncommon, but its incidence is rising. Women often recover cardiac function, but long-lasting morbidity and mortality are not infrequent. Management of peripartum cardiomyopathy is largely limited to the same neurohormonal antagonists used in other forms of cardiomyopathy, and no proven disease-specific therapies exist yet. Research in the past decade has suggested that peripartum cardiomyopathy is caused by vascular dysfunction, triggered by late-gestational maternal hormones. Most recently, information has also indicated that many cases of peripartum cardiomyopathy have genetic underpinnings. We review here the known epidemiology, clinical presentation, and management of peripartum cardiomyopathy, as well as the current knowledge of the pathophysiology of the disease.

Echocardiography in Pregnancy: Part 2.

The prevalence of pregnant women with cardiovascular heart disease is increasing. Transthoracic echocardiography is safe during pregnancy, and it is an important diagnostic tool in pregnant women with established heart disease in order to monitor ventricular and valvular anatomy and function. In addition, it can be used to delineate cardiac anatomy in complex congenital heart disease and help stratify maternal risk during pregnancy. This review will focus on the use of echocardiography in the diagnosis and management of pregnant women with common congenital lesions and with prosthetic valves.

Echocardiography in Pregnancy: Part 1.

Cardiovascular disease (CVD) remains the leading cause of maternal mortality, and clinical diagnosis of CVD in women during pregnancy is challenging. Pregnant women with known heart disease require careful multidisciplinary management by obstetric and medical teams to assess for maternal and fetal risk. Echocardiography is a safe and effective diagnostic tool indicated in pregnant women with cardiac symptoms or women with known cardiac disease for appropriate selection of women who require close monitoring of cardiac condition and valvular function. Echocardiography is the single most important clinical tool to diagnose and manage heart disease during pregnancy. Echocardiography is able to characterize cardiac structural abnormalities and corresponding hemodynamic changes, identifies heart diseases that are poorly tolerated in pregnancy, and helps select patients who may require a cesarean delivery because of hemodynamic instability. An understanding of the physiologic alterations including increased heart rate, blood volume, and cardiac output as well as the decreased vascular resistance is important for early recognition and monitoring of the consequences of cardiac disease in pregnancy. This review will focus on common acquired cardiac lesions encountered during pregnancy and the role of echocardiography in the diagnosis and management of these diseases.

Cardiorenal interactions in acute decompensated heart failure: contemporary concepts facing emerging controversies.

Simultaneous dysfunction of the heart and the kidney represents a distinct spectrum of disease states composed of complex clinical scenarios with adverse outcomes. Worsening renal function (WRF) in the setting of acute decompensated heart failure (ADHF) is one such clinical setup for which the underlying mechanisms are poorly understood. Apparent discrepancies exist between the emerging data on the cardiorenal interactions of patients with ADHF and contemporary concepts such as the low forward flow or the high backward pressure hypotheses. The findings of recent retrospective studies also suggest that apparent "improvement in renal function" might be yet another risk factor for untoward outcomes in this patient population, further challenging our current understanding of the cardiorenal interactions. Besides, these data do not seem to fully support our conventional thinking about other aspects of these interactions such as the independent adverse impact of WRF on the outcomes of patients with ADHF, pointing to congestion as a possibly overlooked factor. In this article, we provide an overview of these emerging controversial issues with the goal of identifying the areas where clinical research could be most helpful, because it is of paramount importance to characterize the pathways leading to WRF in ADHF to develop a mechanistically relevant management strategy. Although the paucity of data coupled with the complexity of this field precludes any firm conclusion, these discussions are meant to prompt clinicians and researchers to revisit a number of long-believed concepts surrounding the cardiorenal interactions in ADHF.

Association of hyponatremia to diuretic response and incidence of increased serum creatinine levels in hospitalized patients with acute decompensated heart failure.

OBJECTIVES: Although hyponatremia is a prognostic factor in acute heart failure (AHF), its influence on the acute clinical course of heart failure is unknown. Our objective was to evaluate the association of hyponatremia with diuretic response, renal function, and clinical outcomes in AHF. METHODS: A retrospective study included 499 hospitalized AHF patients treated with intravenous loop diuretics for ≥48 h. Patients were grouped by nadir sodium concentrations (normonatremic, NN) ≥135 mEq/l, (mild hyponatremia, MHN) 130-134 mEq/l, and (moderate to severe hyponatremia, MSHN) <130 mEq/l. Association to diuretic response and clinical outcome was assessed. RESULTS: The incidence of hyponatremia was 54% (36% MHN, 18% MSHN). Maximum diuretic dose (furosemide equivalents: NN 84 ± 132 mg/day vs. MHN 114 ± 165 mg/day vs. MSHN 249 ± 450 mg/day, p < 0.001) and incidence of diuretic regimen escalation (NN 11% vs. MHN 16% vs. MSHN 44%, p < 0.001) were significantly higher in patients experiencing hyponatremia. Hyponatremia was also associated with a higher incidence of acute increases in serum creatinine (NN 27% vs. MHN 45% vs. MSHN 63%, p < 0.001), greater increases in blood urea nitrogen, longer hospital stay, and higher mortality. Outcome disparities to NN patients were similar whether hyponatremia was acute or present upon admission. CONCLUSIONS: Acute or admission hyponatremia, especially <130 mEq/l, in AHF patients is associated with greater diuretic requirements, higher incidence of serum creatinine increases, and a poorer outcome. Alternative treatments warrant evaluation in these patients.

Successful Pregnancy After Left Ventricular Assist Device Explantation for Myocardial Recovery.

A 36 year old woman with history of heart failure and left ventricular assist device (LVAD) implantation, with subsequent explantation after myocardial recovery, presented for management of preconception counseling and subsequent pregnancy. To our knowledge, this case represents the first documented successful pregnancy after LVAD explantation. Management details are provided, and relevant literature is reviewed.

Differences in clinical profile of African-American women with peripartum cardiomyopathy in the United States.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare and heterogeneous disease with a higher prevalence in African Americans (AAs) in the USA. The clinical features and prognosis of PPCM in AAs have not been sufficiently characterized. METHODS: We studied 52 AA patients with PPCM and compared clinical characteristics and outcome with those of 104 white patients. RESULTS: AA patients were significantly younger (26 ± 7 vs 30 ± 6 years; P < .001), had a higher prevalence of gestational hypertension (61% vs 41%; P = .03), and were diagnosed more commonly postpartum rather then antepartum (83% vs 64%; P = .03). The rate of left ventricular (LV) recovery (LV ejection fraction [LVEF] ≥50%) was significantly lower in AAs (40% vs 61%; P = .02). AA women also had a larger LV end-diastolic diameter (57 ± 10 vs 51 ± 6 mm; P = .004) as well as lower LVEF (40% ± 16.7% vs 46% ± 14%; P = .002) at the last follow-up. Moreover, AA patients had a significantly higher incidence of the combined end points of mortality and cardiac transplantation (P = .03) and showed a strong trend (P = .09) for increased mortality. CONCLUSIONS: AA patients with PPCM in the USA have a different clinical profile and worse prognosis compared with white patients. Further research to evaluate potentially correctable causes for these differences is warranted.

Cardiovascular imaging of the pregnant patient.

OBJECTIVE: The purpose of this review is to describe the selection and methods of imaging of pregnant women with cardiovascular conditions. CONCLUSION: Common cardiovascular conditions may occur in 1% of all pregnant women. The selection and methods of imaging studies require thoughtful planning. Use of radiation, radiopharmaceuticals, and contrast agents should be minimized. Pulmonary and cardiac CT angiography deliver minimal fetal radiation, and ventilation-perfusion scintigraphy presents relatively low fetal irradiation. Cardiac catheterization, coronary angiography, and electrophysiologic procedures, including complex interventions, also cause relatively low fetal exposure. Even nuclear cardiology procedures are unlikely to exceed negligible-risk (50 mGy cutoff) fetal radiation doses.

Mechanical heart valve thrombosis in pregnancy.

Effective anticoagulation is critical in patients with mechanical prosthetic heart valve (MPHV), but remains challenging in pregnancy because both oral anticoagulation and heparins are associated with important fetal and maternal risks. A 33-year-old high-risk pregnant woman presented with MPHV thrombosis during early pregnancy. Resolution of the thrombus and eventual resumption of normal prosthetic mitral valve function was obtained through treatment with low-molecular weight heparin (LMWH). This case of early pregnancy MPHV thrombosis emphasized the importance of adequate initial coagulation prior to pregnancy and the potential need to extend measurements to both peak and trough levels to assure an adequate level of anticoagulation in women with MPHV treated with LMWH during pregnancy.