Sex Differences in Heart Failure With Reduced Ejection Fraction in the GALACTIC-HF Trial.

BACKGROUND: Women with heart failure with reduced ejection fraction (HFrEF) receive less guideline-recommended therapy and experience worse quality of life than men. OBJECTIVES: The authors sought to assess differences in baseline characteristics, outcomes, efficacy, and safety of omecamtiv mecarbil between men and women enrolled in the GALACTIC-HF (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction) study. METHODS: In GALACTIC-HF, patients with symptomatic heart failure with EF of 35% or less, recent heart failure event, and elevated natriuretic peptides were randomized to omecamtiv mecarbil or placebo. The current analysis investigated differences in baseline characteristics, clinical outcomes, and efficacy and safety of omecamtiv mecarbil between men and women. RESULTS: Of 8,232 patients analyzed, 21.2% were women. Women more likely self-identified as being Black, had worse symptoms (lower Kansas City Cardiomyopathy Questionnaire Total Symptom Score [KCCQ-TSS]), and were less likely to be treated with angiotensin receptor/neprilysin inhibitor and devices at baseline. Compared with men, women had lower rates of the primary endpoint (adjusted HR: 0.80, 95% CI: 0.73-0.88). Sex did not significantly modify omecamtiv mecarbil's treatment effect (P interaction = 0.68). Women also had 20% less risk of cardiovascular death, heart failure event, and all-cause death. Women participants had lower rates of serious adverse events. CONCLUSIONS: Women participants of the GALACTIC-HF trial had worse quality of life and were less likely to be treated with guideline-based therapies at baseline. Despite KCCQ-TSS being predictive of poor outcomes in this population, women had a 20% lower risk of an HF event or cardiovascular death compared with men. The beneficial effect of omecamtiv mecarbil did not significantly differ by sex. (Registrational Study With Omecamtiv Mecarbil [AMG 423] to Treat Chronic Heart Failure With Reduced Ejection Fraction [GALACTIC-HF]; NCT02929329).

Omecamtiv Mecarbil in Black Patients With Heart Failure and Reduced Ejection Fraction: Insights From GALACTIC-HF.

BACKGROUND: Omecamtiv mecarbil improves cardiovascular outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Consistency of drug benefit across race is a key public health topic. OBJECTIVES: The purpose of this study was to evaluate the effect of omecamtiv mecarbil among self-identified Black patients. METHODS: In GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) patients with symptomatic HF, elevated natriuretic peptides, and left ventricular ejection fraction (LVEF) ≤35% were randomized to omecamtiv mecarbil or placebo. The primary outcome was a composite of time to first event of HF or cardiovascular death. The authors analyzed treatment effects in Black vs White patients in countries contributing at least 10 Black participants. RESULTS: Black patients accounted for 6.8% (n = 562) of overall enrollment and 29% of U.S. enrollment. Most Black patients enrolled in the United States, South Africa, and Brazil (n = 535, 95%). Compared with White patients enrolled from these countries (n = 1,129), Black patients differed in demographics, comorbid conditions, received higher rates of medical therapy and lower rates of device therapies, and experienced higher overall event rates. The effect of omecamtiv mecarbil was consistent in Black vs White patients, with no difference in the primary endpoint (HR = 0.83 vs 0.88, P-interaction = 0.66), similar improvements in heart rate and N-terminal pro-B-type natriuretic peptide, and no significant safety signals. Among endpoints, the only nominally significant treatment-by-race interaction was the placebo-corrected change in blood pressure from baseline in Black vs White patients (+3.4 vs -0.7 mm Hg, P for interaction = 0.02). CONCLUSIONS: GALACTIC-HF enrolled more Black patients than other recent HF trials. Black patients treated with omecamtiv mecarbil had similar benefit and safety compared with White counterparts.

Efficacy of omecamtiv mecarbil in heart failure with reduced ejection fraction according to N-terminal pro-B-type natriuretic peptide level: insights from the GALACTIC-HF trial.

AIM: N-terminal pro-B-type natriuretic peptide (NT-proBNP) is predictive of both outcomes and response to treatment in patients with heart failure with reduced ejection fraction (HFrEF). The aim of this study was to examine the effect of the cardiac myosin activator omecamtiv mecarbil according to baseline NT-proBNP level in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure trial (GALACTIC-HF). METHODS AND RESULTS: The primary outcome was the composite of a worsening heart failure event (urgent clinic visit, emergency department visit, or hospitalization) or cardiovascular death. We prespecified analysis of the effect of treatment according to baseline NT-proBNP (≤ median, > median), excluding individuals with atrial fibrillation/flutter (AF/AFL). Of the 8232 patients analysed, 8206 had an available baseline NT-proBNP measurement. Among the 5971 patients not in AF/AFL, the median (Q1-Q3) NT-proBNP level was 1675 (812-3579) pg/ml. Hazard ratios (HR) for the effect of omecamtiv mecarbil, compared with placebo, for the primary endpoint in patients without AF/AFL were: ≤ median 0.94 (95% confidence interval [CI] 0.80-1.09), > median 0.81 (0.73-0.90) (p-interaction = 0.095); for the overall population (including patients with AF/AFL) the HRs were ≤ median 1.01 (0.90-1.15) and > median 0.88 (0.80-0.96) (p-interaction = 0.035). There was an interaction between treatment and NT-proBNP, examined as a continuous variable, with greater effect of omecamtiv mecarbil on the primary outcome in patients with a higher baseline NT-proBNP (p-interaction = 0.086). CONCLUSIONS: In GALACTIC-HF, the benefit of omecamtiv mecarbil appeared to be larger in patients with higher baseline NT-proBNP levels, especially in patients without AF/AFL. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02929329; EudraCT number, 2016-002299-28.

Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR): design and methodology.

BACKGROUND: Cardiac disease in pregnancy is a major contributor to maternal mortality in high, middle and low-income countries. Availability of data on outcomes of pregnancy in women with heart disease is important for planning resources to reduce maternal mortality. Prospective data on outcomes and risk predictors of mortality in pregnant women with heart disease (PWWHD) from low- and middle-income countries are scarce. METHODS: The Tamil Nadu Pregnancy and Heart Disease Registry (TNPHDR) is a prospective, multicentric and multidisciplinary registry of PWWHD from 29 participating sites including both public and private sectors, across the state of Tamil Nadu in India. The TNPHDR is aimed to provide data on incidence of maternal and fetal outcomes, adverse outcome predictors, applicability of the modified World Health Organization (mWHO) classification of maternal cardiovascular risk and the International risk scoring systems (ZAHARA and CARPREG I & II) in Indian population and identify possible gaps in the existing management of PWWHD. Pregnancy and heart teams will be formed in all participating sites. Baseline demographic, clinical, laboratory and imaging parameters, data on counselling received, antenatal triage and management, peripartum management and postpartum care will be collected from 2500 eligible participants as part of the TNPHDR. Participants will be followed up at one, three and six-months after delivery/termination of pregnancy to document study outcomes. Predictors of maternal and foetal outcome will be identified. DISCUSSION: The TNPHDR will be the first representative registry from low- and middle-income countries aimed at providing crucial information on pregnancy outcomes and risk predictors in PWWHD. The results of TNPHDR could help to formulate steps for improved care and to generate a customised and practical guideline for managing pregnancy in women with heart disease in limited resource settings. TRIAL REGISTRATION: The TNPHDR is registered under Clinical Trials Registry-India ( CTRI/2020/01/022736 ).

Contemporary Diagnosis and Management of Rheumatic Heart Disease: Implications for Closing the Gap: A Scientific Statement From the American Heart Association.

The global burden of rheumatic heart disease continues to be significant although it is largely limited to poor and marginalized populations. In most endemic regions, affected patients present with heart failure. This statement will seek to examine the current state-of-the-art recommendations and to identify gaps in diagnosis and treatment globally that can inform strategies for reducing disease burden. Echocardiography screening based on World Heart Federation echocardiographic criteria holds promise to identify patients earlier, when prophylaxis is more likely to be effective; however, several important questions need to be answered before this can translate into public policy. Population-based registries effectively enable optimal care and secondary penicillin prophylaxis within available resources. Benzathine penicillin injections remain the cornerstone of secondary prevention. Challenges with penicillin procurement and concern with adverse reactions in patients with advanced disease remain important issues. Heart failure management, prevention, early diagnosis and treatment of endocarditis, oral anticoagulation for atrial fibrillation, and prosthetic valves are vital therapeutic adjuncts. Management of health of women with unoperated and operated rheumatic heart disease before, during, and after pregnancy is a significant challenge that requires a multidisciplinary team effort. Patients with isolated mitral stenosis often benefit from percutaneous balloon mitral valvuloplasty. Timely heart valve surgery can mitigate the progression to heart failure, disability, and death. Valve repair is preferable over replacement for rheumatic mitral regurgitation but is not available to the vast majority of patients in endemic regions. This body of work forms a foundation on which a companion document on advocacy for rheumatic heart disease has been developed. Ultimately, the combination of expanded treatment options, research, and advocacy built on existing knowledge and science provides the best opportunity to address the burden of rheumatic heart disease.

Influence of socioeconomic factors on pregnancy outcome in women with structural heart disease.

OBJECTIVE: Cardiac disease is the leading cause of indirect maternal mortality. The aim of this study was to analyse to what extent socioeconomic factors influence the outcome of pregnancy in women with heart disease. METHODS: The Registry of Pregnancy and Cardiac disease is a global prospective registry. For this analysis, countries that enrolled ≥10 patients were included. A combined cardiac endpoint included maternal cardiac death, arrhythmia requiring treatment, heart failure, thromboembolic event, aortic dissection, endocarditis, acute coronary syndrome, hospitalisation for cardiac reason or intervention. Associations between patient characteristics, country characteristics (income inequality expressed as Gini coefficient, health expenditure, schooling, gross domestic product, birth rate and hospital beds) and cardiac endpoints were checked in a three-level model (patient-centre-country). RESULTS: A total of 30 countries enrolled 2924 patients from 89 centres. At least one endpoint occurred in 645 women (22.1%). Maternal age, New York Heart Association classification and modified WHO risk classification were associated with the combined endpoint and explained 37% of variance in outcome. Gini coefficient and country-specific birth rate explained an additional 4%. There were large differences between the individual countries, but the need for multilevel modelling to account for these differences disappeared after adjustment for patient characteristics, Gini and country-specific birth rate. CONCLUSION: While there are definite interregional differences in pregnancy outcome in women with cardiac disease, these differences seem to be mainly driven by individual patient characteristics. Adjustment for country characteristics refined the results to a limited extent, but maternal condition seems to be the main determinant of outcome.

Organisation of care for pregnancy in patients with congenital heart disease.

Improvements in surgery have resulted in more women with repaired congenital heart disease (CHD) surviving to adulthood. Women with CHD, who wish to embark on pregnancy require prepregnancy counselling. This consultation should cover several issues such as the long-term prognosis of the mother, fertility and miscarriage rates, recurrence risk of CHD in the baby, drug therapy during pregnancy, estimated maternal risk and outcome, expected fetal outcomes and plans for pregnancy. Prenatal genetic testing is available for those patients with an identified genetic defect using pregestational diagnosis or prenatal diagnosis chorionic villus sampling or amniocentesis. Centralisation of care is needed for high-risk patients. Finally, currently there are no recommendations addressing the issue of the delivery. It is crucial that a dedicated plan for delivery should be available for all cardiac patients. The maternal mortality in low-income to middle-income countries is 14 times higher than in high-income countries and needs additional aspects and dedicated care.

A global view of pulmonary hypertension.

Pulmonary hypertension is a substantial global health issue. All age groups are affected with rapidly growing importance in elderly people, particularly in countries with ageing populations. Present estimates suggest a pulmonary hypertension prevalence of about 1% of the global population, which increases up to 10% in individuals aged more than 65 years. In almost all parts of the world, left-sided heart and lung diseases have become the most frequent causes of pulmonary hypertension. About 80% of affected patients live in developing countries, where pulmonary hypertension is frequently associated with congenital heart disease and various infectious disorders, including schistosomiasis, HIV, and rheumatic heart disease. These forms of pulmonary hypertension occur predominantly in those younger than 65 years. Independently of the underlying disease, the development of pulmonary hypertension is associated with clinical deterioration and a substantially increased mortality risk. Global research efforts are needed to establish preventive strategies and treatments for the various types of pulmonary hypertension.

The way forward for clinical research in Cameroon: first scientific and research day in Douala, 2014.

There is a huge need for health research to support contextually relevant health service and policy solutions to better the health of populations in sub-Saharan Africa. This need contrasts with the very timid engagement of healthcare practitioners in research in the region.It is against this background that the Douala General Hospital (a tertiary-care hospital in Cameroon), under the stewardship of its chief executive officer, organised the first annual scientific and research day in October 2014. This maiden event saw the participation of local research leaders and the eminent director of the South African Hatter Institute for Cardiovascular Research in Africa, who co-chaired the event. The aim was to educate students, clinicians and junior researchers on the importance of clinical research and evidence-based medicine around the leading theme of the event: action for clinical research and good medical practice.Several abstracts were presented, covering various aspects of medicine, including cardiology, rheumatology, paediatrics, pulmonology, HIV medicine, and obstetrics and gynaecology, together with key lectures on cardiac disease and pregnancy, and plenary sessions on research methodology, scientific writing and publishing. It is hoped that this event will enhance clinical research and the dissemination of research findings to improve evidence-based clinical practice in the country.