Focus on cardiomyopathy and heart failure

This edition of the Journal presents the important topic of risk stratification in patients with hypertrophic cardiomyopathy undergoing sport participation. Also, the issue of heart failure stratification and treatment is addressed in different settings. Finally, the role of pre-eclampsia is presented in two studies. Hypertrophic cardiomyopathy (HCM) has long been regarded as the leading cause of sudden cardiac death (SCD) in young athletes. However, despite the abundance of studies examining the relationship between HCM and SCD in athletes,1,2 significant gaps in our understanding continue to exist. This has been attributed to the lack of prospective studies, including the influence of sustained exercise and sport on cardiac remodelling in HCM athletes and the impact of sport participation on clinical outcome.3 In addition, investigations to manage comorbidities have been sparked by concern about the negative effects of a sedentary lifestyle and the alarming prevalence of obesity in HCM cohorts. The most recent studies on the effects of exercise on cardiac remodelling and outcomes in HCM patient are here reviewed and discussed.4 The authors conclude that the risk associated with sport was previously overestimated, and that tailored exercise programmes represent an important strategy to counteract the deleterious effects of sedentary behaviour and obesity. Although the risk of SCD cannot be predicted solely based on conventional risk factors, especially in athletes due to the dearth of data derived from this population, it is crucial to estimate the baseline risk of SCD: individuals without any known risk factors, free from symptoms and arrhythmias, and with normal physical function should be considered at very low risk. Thus, after an individual evaluation, these people should have no restrictions on leisurely sport and exercise regimens. For all the remaining individuals, with the probable exception of those activities where the incidence of syncope may be connected with harm or death (such as scuba diving, rock climbing, motor racing, and free downhill skiing), choosing a discipline still primarily depends on the patient's desire and motivation. Furthermore, according to current recommendations, vigorous exercise regimens and involvement in competitive sports may be considered only following individual assessment and collaborative decision-making (Class IIb, LOE C). Cardiac rehabilitation (CR) is defined as a multidisciplinary program that includes exercise training, cardiac risk factor modification, psychosocial assessment, and outcomes assessment. In patients with heart failure (HF), exercise training and other components of CR are recommended because they lead to considerable improvements in quality of life, functional ability, exercise performance, and hospitalisations linked to HF.5,6 However, there are still a lack of cohort studies that comprehensively evaluate the efficacy of CR in real-world settings. Using a very large Japanese administrative database, the authors were here interested in exploring the multifactorial effects of outpatient CR in patients who had been hospitalised for acute HF, including morbidity, rehospitalization, and utilisation of medical resources.7 Among 250 528 patients, 17 884 received outpatient CR. After propensity score matching, the CR group was linked with a lower risk of all-cause mortality and rehospitalization for HF. At 1 year, the proportion of HF patients using medications based on guidelines was greater in the CR group. Similar costs were spent by both groups from the index hospitalisation to 1.5 years following admission. Ventilatory disturbances are clearly recognized as a marker of severity in HF.8 Since the first description of Cheyne–Stokes respiration, the attention has been shifted to the exercise oscillatory ventilation (EOV) observed during effort. Despite the understanding of the main pathophysiological mechanisms, a large incertitude still exists in defining the diagnostic criteria with the optimal sensitivity and specificity.9 In this issue, Cunha et al.10 tried to overcome the problem testing the prognostic significance of loop gain (LG) in a cohort of HF subjects with reduced ejection fraction. LG is a measure of the magnitude of ventilatory correction after a disturbance, estimated with additional mathematical analysis of raw ventilatory data. Using this approach, the authors were able to show the independent prognostic significance of LG, outperforming the EOV variable, even after correcting for the most important cardiopulmonary exercise test variables and NTproBNP. The paper is remarkable for the new and promising approach in identifying ventilatory disturbances with prognostic impact in HF. Degenerative aortic valve disease is a gradual process starting with valve thickening, progressing with fibrosis and calcification until severe restriction of leaflets. Even the early stage of the process, called aortic valve sclerosis (AVS), has been associated with cardiovascular morbidity and mortality. In this issue, Yoshida et al.11 explored the pathophysiological mechanisms underlying AVS, examining 962 subjects with normal left ventricle (LV) geometry. They identified no AVS in 767 (79.7%) individuals, AV thickening in 74 (7.7%), calcification on one leaflet in 87 (9.0%), and calcification on ≥2 leaflets in 34 (3.5%). Interestingly, multivariable logistic regression showed that earlier (thickening) and later (calcification) stages of valve disease were associated with subclinical LV diastolic impairment (E/e’ ≥ 13), whilst only the latest stage of AVS (calcification on ≥2 leaflets) conferred an increased risk of reduced LV global longitudinal strain. The study nicely remarks the importance of subclinical diastolic and systolic dysfunction and its relevance in AVS progression. The ability of anti-diabetic drugs in preventing cardiovascular events is a raising matter of interest. Several classes of drugs have been shown to exert a protective effect, also in subjects without diabetes. In the present issue, He et al.12 focused on glimepiride, a low-cost sulfonylurea widely used to treat diabetes. They presented a prospective cohort study on 509 subjects with type II diabetes and chronic HF with reduced ejection fraction (EF < 40%) receiving glimepiride, matched with 509 subjects treated with different anti-diabetic drugs. They were able to show a significant protective effect on all-cause mortality (adjusted HR, 0.47; 95% CI 0.35–0.63; P < 0.001), cardiovascular mortality (adjusted HR, 0.34; 95% CI, 0.24–0.48; P < 0.001), and also hospitalizations for HF, myocardial infarct, and stroke. Interestingly, they found a dose-related effect and a positive association with high levels of epoxyeicosatrienoic acid, an endogenous factor inhibiting inflammation, endothelial dysfunction, cardiac remodelling, and fibrosis. The study expands the evidence for the use of anti-diabetic drugs to prevent cardiovascular events. Pregnancy is frequently considered a cardiometabolic stress test, with pregnancy complications indicating early cardiovascular risk.13 In fact, pregnancy complications like hypertensive disorders, gestational diabetes mellitus, preterm birth, and delivery of a small-for-gestational-age infant increase the risk of chronic hypertension, type 2 diabetes mellitus, dyslipidemia, and chronic kidney disease in women.14 Furthermore, there are important ethnic differences in the incidence of both pregnancy complications and cardiovascular risk. However, little is known about the potential value of pregnancy complications as an indicator of high cardiovascular risk among ethnic minority populations. Here, the study by J. Burger et al.15 examined this association in 2466 parous women of Dutch, South-Asian Surinamese, African Surinamese, Ghanaian, Turkish, and Moroccan origin. High blood pressure during pregnancy or premature delivery increased the risk of persistent hypertension or renal disease later in life by double. Diabetes in pregnancy increased the risk of type 2 diabetes eightfold. South-Asian, African, and Ghanaian women in the Netherlands experienced greater pregnancy problems and cardiovascular risk factors than Dutch women. Pre-eclampsia, a dangerous obstetric complication that affects 2–8% of all pregnancies, is defined by incident hypertension as well as other symptoms of organ failure. Women with a history of pre-eclampsia are two times more likely to develop cardiovascular disease, including acute myocardial infarction (AMI) and ischemic stroke in comparison to women without a history. However, little is known about when to initiate monitoring for cardiovascular disease in this group of women. In this issue of the Journal, in a nationwide register data from more than 1 million Danish women having a live birth or stillbirth between 1978 and 2017, the timing and trajectory of AMI and ischemic stroke risk were compared between women with and without a history of pre-eclampsia.16 In comparison to women who did not experience pre-eclampsia in their first pregnancy, up to twice as many women with a first pregnancy complicated by pre-eclampsia had AMI or ischemic stroke within 20 years of delivery. Although the risk was highest in women aged 30–39 and within ten years after pre-eclampsia, the relative hazards persisted even 20 years later and in older women.