Cardiovascular diseases are a major cause of complications in pregnancy worldwide, and the number of patients who develop cardiac problems during pregnancy is increasing. Peripartum cardiomyopathy ...(PPCM) is a potentially life-threatening heart disease that emerges towards the end of pregnancy or in the first months postpartum, in previously healthy women. Symptoms and signs of PPCM are similar to those in patients with idiopathic dilated cardiomyopathy. The incidence varies geographically, most likely because of socioeconomic and genetic factors. The syndrome is associated with a high morbidity and mortality, and diagnosis is often delayed. Various mechanisms have been investigated, including the hypothesis that unbalanced peripartum or postpartum oxidative stress triggers the proteolytic cleavage of the nursing hormone prolactin into a potent antiangiogenic, proapoptotic, and proinflammatory 16 kDa fragment. This theory provides the basis for the discovery of disease-specific biomarkers and promising novel therapeutic targets. In this Review, we describe the latest understanding of the epidemiology, pathophysiology, and novel treatment strategies for patients with PPCM.
Sex differences in heart failure Lam, Carolyn S P; Arnott, Clare; Beale, Anna L ...
European heart journal,
12/2019, Volume:
40, Issue:
47
Journal Article
Peer reviewed
Open access
Abstract
The overall lifetime risk of heart failure (HF) is similar between men and women, however, there are marked sex differences in the landscape of this condition that are both important and ...under-recognized. Men are predisposed to HF with reduced ejection fraction (HFrEF), whereas women predominate in HF with preserved ejection fraction (HFpEF). Sex differences are also notable in the penetrance of genetic cardiomyopathies, risk factors, e.g. breast cancer which may be associated with cancer treatment-induced cardiomyopathy, as well as sex-specific conditions such as peripartum cardiomyopathy (PPCM). This review outlines the key sex differences with respect to clinical characteristics, pathophysiology, and therapeutic responses to HF treatments. Finally, we address important differences in the prognosis of HF. A central hypothesis is that the higher risk of HFrEF in men compared to women may be attributable to their predisposition to macrovascular coronary artery disease and myocardial infarction, whereas coronary microvascular dysfunction/endothelial inflammation has been postulated to play a key role in HFpEF and maybe the common link among HF syndromes that women are predisposed to Takotsubo cardiomyopathy, PPCM, and breast cancer radiotherapy-induced cardiomyopathy. Under-pinning current sex disparities in HF, there is a paucity of women recruited to HF clinical trials (20–25% of cohorts) and thus treatment guidelines are predominantly based on male-derived data. Large gaps in knowledge exist in sex-specific mechanisms, optimal drug doses for women and sex-specific criteria for device therapy.
Abstract
Peripartum cardiomyopathy (PPCM) is a disease that occurs globally in all ethnic groups and should be suspected in any peripartum women presenting with symptoms and signs of heart failure, ...towards the end of pregnancy or in the months following delivery, with confirmed left ventricular dysfunction. After good history taking, all women should be thoroughly assessed, and alternative causes should be excluded. Urgent cardiac investigations with electrocardiogram and natriuretic peptide measurement (if available) should be performed. Echocardiography follows as the next step in investigation. Patients with abnormal cardiac investigations should be urgently referred to a cardiology team for expert management. Referral for genetic work-up should be considered if there is a family history of cardiomyopathy or sudden death. PPCM is a disease with substantial maternal and neonatal morbidity and mortality. Maternal mortality rates range widely, from 0% to 30%, depending on the ethnic background and geographic region. Just under half of women experience myocardial recovery. Remarkable advances in the comprehension of the pathogenesis and in patient management and therapy have been achieved, largely due to team efforts and close collaboration between basic scientists, cardiologists, intensive care specialists, and obstetricians. This review summarizes current knowledge of PPCM genetics, pathophysiology, diagnostic approach, management, and outcome.
Graphical Abstract
Non-communicable diseases (NCDs) are the second common cause of death in sub-Saharan Africa (SSA) accounting for about 35% of all deaths, after a composite of communicable, maternal, neonatal, and ...nutritional diseases. Despite prior perception of low NCDs mortality rates, current evidence suggests that SSA is now at the dawn of the epidemiological transition with contemporary double burden of disease from NCDs and communicable diseases. In SSA, cardiovascular diseases (CVDs) are the most frequent causes of NCDs deaths, responsible for approximately 13% of all deaths and 37% of all NCDs deaths. Although ischemic heart disease (IHD) has been identified as the leading cause of CVDs mortality in SSA followed by stroke and hypertensive heart disease from statistical models, real field data suggest IHD rates are still relatively low. The neglected endemic CVDs of SSA such as endomyocardial fibrosis and rheumatic heart disease as well as congenital heart diseases remain unconquered. While the underlying aetiology of heart failure among adults in high-income countries (HIC) is IHD, in SSA the leading causes are hypertensive heart disease, cardiomyopathy, rheumatic heart disease, and congenital heart diseases. Of concern is the tendency of CVDs to occur at younger ages in SSA populations, approximately two decades earlier compared to HIC. Obstacles hampering primary and secondary prevention of CVDs in SSA include insufficient health care systems and infrastructure, scarcity of cardiac professionals, skewed budget allocation and disproportionate prioritization away from NCDs, high cost of cardiac treatments and interventions coupled with rarity of health insurance systems. This review gives an overview of the descriptive epidemiology of CVDs in SSA, while contrasting with the HIC and highlighting impediments to their management and making recommendations.
- The burden of non-communicable diseases including cardiovascular diseases is rising in SSA.- Levels of hypertension diagnosis, treatment, and control are low at <40%, <35%, and 10-20%, respectively, and more than 40% of patients with diabetes are not aware of their diagnosis in SSA.- SSA has 23% of the world's prevalent rheumatic heart disease cases.- The leading causes of heart failure in SSA are hypertensive heart disease, cardiomyopathy, and rheumatic heart disease, with ischemic heart disease accounting for <10% of cases compared to >50% in high-income countries.
Summary Background Studies have challenged the appropriateness of accepted blood pressure targets. We hypothesised that different levels of low blood pressure are associated with benefit for some, ...but harm for other outcomes. Methods In this analysis, we assessed the previously reported outcome data from high-risk patients aged 55 years or older with a history of cardiovascular disease, 70% of whom had hypertension, from the ONTARGET and TRANSCEND trials investigating ramipril, telmisartan, and their combination, with a median follow-up of 56 months. Detailed descriptions of randomisation and intervention have already been reported. We analysed the associations between mean blood pressure achieved on treatment; prerandomisation baseline blood pressure; or time-updated blood pressure (last on treatment value before an event) on the composite outcome of cardiovascular death, myocardial infarction, stroke, and hospital admission for heart failure; the components of the composite outcome; and all-cause death. Analysis was done by Cox regression analysis, ANOVA, and χ2 . These trials were registered with ClinicalTrials.gov , number NCT00153101. Findings Recruitment for ONTARGET took place between Dec 1, 2001, and July 31, 2008. TRANSCEND took place between Nov 1, 2001, and May 30, 2004. 30 937 patients were recruited from 733 centres in 40 countries and followed up for a median of 56 months. In ONTARGET, 25 127 patients known to be tolerant to angiotensin-converting-enzyme (ACE)-inhibitors were randomly assigned after a run-in period to oral ramipril 10 mg/day (n=8407), telmisartan 80 mg/day (n=8386), or the combination of both (n=8334). In TRANSCEND, 5810 patients who were intolerant to ACE-inhibitors were randomly assigned to oral telmisartan 80 mg/day (n=2903) or placebo (n=2907). Baseline systolic blood pressure (SBP) 140 mm Hg or higher was associated with greater incidence of all outcomes compared with 120 mm Hg to less than 140 mm Hg. By contrast, a baseline diastolic blood pressure (DBP) less than 70 mm Hg was associated with the highest risk for most outcomes compared with all DBP categories 70 mm Hg or more. In 4052 patients with SBP less than 120 mm Hg on treatment, the risk of the composite cardiovascular outcome (adjusted hazard ratio HR 1·14, 95% CI 1·03–1·26), cardiovascular death (1·29, 1·12–1·49), and all deaths (1·28, 1·15–1·42) were increased compared with those in whom SBP was 120–140 mm Hg during treatment (HR 1 for all outcomes, n=16099). No harm or benefit was observed for myocardial infarction, stroke, or hospital admission for heart failure. Mean achieved SBP more accurately predicted outcomes than baseline or time-updated SBP, and was associated with the lowest risk at approximately 130 mm Hg, and at 110–120 mm Hg risk increased for the combined outcome, cardiovascular death, and all-cause death except stroke. A mean DBP less than 70 mm Hg (n=5352) during treatment was associated with greater risk of the composite primary outcome (HR 1·31, 95% CI 1·20–1·42), myocardial infarction (1·55, 1·33–1·80), hospital admission for heart failure (1·59, 1·36–1·86) and all-cause death (1·16, 1·06–1·28) than a DBP 70–80 mm Hg (14 305). A pretreatment and mean on-treatment DBP of about 75 mm Hg was associated with the lowest risk. Interpretation Mean achieved SBP less than 120 mm Hg during treatment was associated with increased risk of cardiovascular outcomes except for myocardial infarction and stroke. Similar patterns were observed for DBP less than 70 mm Hg, plus increased risk for myocardial infarction and hospital admission for heart failure. Very low blood pressure achieved on treatment was associated with increased risks of several cardiovascular disease events. These data suggest that the lowest blood pressure possible is not necessarily the optimal target for high-risk patients, although it is not possible to rule out some effect of reverse causality. Funding Boehringer Ingelheim.
Peripartum cardiomyopathy (PPCM) is a potentially life‐threatening condition typically presenting as heart failure with reduced ejection fraction (HFrEF) in the last month of pregnancy or in the ...months following delivery in women without another known cause of heart failure. This updated position statement summarizes the knowledge about pathophysiological mechanisms, risk factors, clinical presentation, diagnosis and management of PPCM. As shortness of breath, fatigue and leg oedema are common in the peripartum period, a high index of suspicion is required to not miss the diagnosis. Measurement of natriuretic peptides, electrocardiography and echocardiography are recommended to promptly diagnose or exclude heart failure/PPCM. Important differential diagnoses include pulmonary embolism, myocardial infarction, hypertensive heart disease during pregnancy, and pre‐existing heart disease. A genetic contribution is present in up to 20% of PPCM, in particular titin truncating variant. PPCM is associated with high morbidity and mortality, but also with a high probability of partial and often full recovery. Use of guideline‐directed pharmacological therapy for HFrEF is recommended in all patients respecting contraindications during pregnancy/lactation. The oxidative stress‐mediated cleavage of the hormone prolactin into a cardiotoxic fragment has been identified as a driver of PPCM pathophysiology. Pharmacological blockade of prolactin release using bromocriptine as a disease‐specific therapy in addition to standard therapy for heart failure treatment has shown promising results in two clinical trials. Thresholds for devices (implantable cardioverter‐defibrillators, cardiac resynchronization therapy and implanted long‐term ventricular assist devices) are higher in PPCM than in other conditions because of the high rate of recovery. The important role of education and counselling around contraception and future pregnancies is emphasised.
Summary Background The Heart of Soweto Study aims to increase our understanding of the characteristics and burden imposed by heart disease in an urban African community in probable epidemiological ...transition. We aimed to investigate the clinical range of disorders related to cardiovascular disease in patients presenting for the first time to a tertiary-care centre. Methods From Jan 1 to Dec 31, 2006, we recorded data for 4162 patients with confirmed cases of cardiovascular disease (1593 newly diagnosed and 2569 previously diagnosed and under treatment) who attended the cardiology unit at the Chris Hani Baragwanath Hospital in Soweto, South Africa. We developed a prospectively designed registry and gathered detailed clinical data relating to the presentation, investigations, and treatment of all 1593 patients with newly diagnosed cardiovascular disease. Findings Most patients were black Africans (n=1359 85%), and the study population contained more women (n=939 59%) than men. Women were slightly younger than were men (mean 53 SD 16 years vs 55 15 years; p=0·031), with 399 (25%) patients younger than 40 years. Heart failure was the most common primary diagnosis (704 cases, 44% of total). Moderate to severe systolic dysfunction was evident in 415 (53%) of 844 identified cases of heart failure, 577 (68%) of which were attributable to dilated cardiomyopathy or hypertensive heart disease, or both. Black Africans were more likely to be diagnosed with heart failure than were the rest of the cohort (739 54% vs 105 45%; odds ratio OR 1·46, 95% CI 1·11–1·94; p=0·009) but were less likely to be diagnosed with coronary artery disease (77 6% vs 88 38%; OR 0·10, 0·07–0·14; p<0·0001). Prevalence of cardiovascular risk factors was very high, with 897 (56%) patients diagnosed with hypertension (190 44% of whom were also obese). Only 209 (13%) patients had no identifiable risk factors, whereas 933 (59%) had several risk factors. Interpretation We noted many threats to the present and future cardiac health of Soweto, including a high prevalence of modifiable risk factors for atherosclerotic disease and a combination of infectious and non-communicable forms of heart disease, with late clinical presentations. Overall, our findings provide strong evidence that epidemiological transition in Soweto, South Africa has broadened the complexity and spectrum of heart disease in this community. This registry will enable continued monitoring of the range of heart disease.
An anti-angiogenic cleaved prolactin fragment is considered causal for peripartum cardiomyopathy (PPCM). Experimental and first clinical observations suggested beneficial effects of the prolactin ...release inhibitor bromocriptine in PPCM.
In this multicentre trial, 63 PPCM patients with left ventricular ejection fraction (LVEF) ≤35% were randomly assigned to short-term (1W: bromocriptine, 2.5 mg, 7 days) or long-term bromocriptine treatment (8W: 5 mg for 2 weeks followed by 2.5 mg for 6 weeks) in addition to standard heart failure therapy. Primary end point was LVEF change (delta) from baseline to 6 months assessed by magnetic resonance imaging. Bromocriptine was well tolerated. Left ventricular ejection fraction increased from 28 ± 10% to 49 ± 12% with a delta-LVEF of + 21 ± 11% in the 1W-group, and from 27 ± 10% to 51 ± 10% with a delta-LVEF of + 24 ± 11% in the 8W-group (delta-LVEF: P = 0.381). Full-recovery (LVEF ≥ 50%) was present in 52% of the 1W- and in 68% of the 8W-group with no differences in secondary end points between both groups (hospitalizations for heart failure: 1W: 9.7% vs. 8W: 6.5%, P = 0.651). The risk within the 8W-group to fail full-recovery after 6 months tended to be lower. No patient in the study needed heart transplantation, LV assist device or died.
Bromocriptine treatment was associated with high rate of full LV-recovery and low morbidity and mortality in PPCM patients compared with other PPCM cohorts not treated with bromocriptine. No significant differences were observed between 1W and 8W treatment suggesting that 1-week addition of bromocriptine to standard heart failure treatment is already beneficial with a trend for better full-recovery in the 8W group.
ClinicalTrials.gov, study number: NCT00998556.
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