Orthostatic hypotension is associated with higher levels of circulating endostatin.

Aims: The pathophysiology of orthostatic hypotension (OH), a common clinical condition, associated with adverse outcomes, is incompletely understood. We examined the relationship between OH and circulating endostatin, an endogenous angiogenesis inhibitor with antitumour effects proposed to be involved in blood pressure (BP) regulation. Methods and results: We compared endostatin levels in 146 patients with OH and 150 controls. A commercial chemiluminescence sandwich immunoassay was used to measure circulating levels of endostatin. Linear and multivariate logistic regressions were conducted to test the association between endostatin and OH. Endostatin levels were significantly higher in OH patients (59 024 ± 2513 pg/mL) vs. controls (44 090 ± 1978pg/mL, P < 0.001). A positive linear correlation existed between endostatin and the magnitude of systolic BP decline upon standing (P < 0.001). Using multivariate analysis, endostatin was associated with OH (adjusted odds ratio per 10% increase of endostatin in the whole study population = 1.264, 95% confidence interval 1.141-1.402), regardless of age, sex, prevalent cancer, and cardiovascular disease, as well as traditional cardiovascular risk factors. Conclusion: Circulating endostatin is elevated in patients with OH and may serve as a potential clinical marker of increased cardiovascular risk in patients with OH. Our findings call for external validation. Further research is warranted to clarify the underlying pathophysiological mechanisms.

Revisiting Diagnosis and Treatment of Hypertrophic Cardiomyopathy: Current Practice and Novel Perspectives.

Sarcomeric hypertrophic cardiomyopathy (HCM) is a prevalent genetic disorder characterised by left ventricular hypertrophy, myocardial disarray, and an increased risk of heart failure and sudden cardiac death. Despite advances in understanding its pathophysiology, treatment options for HCM remain limited. This narrative review aims to provide a comprehensive overview of current clinical practice and explore emerging therapeutic strategies for sarcomeric HCM, with a focus on cardiac myosin inhibitors. We first discuss the conventional management of HCM, including lifestyle modifications, pharmacological therapies, and invasive interventions, emphasizing their limitations and challenges. Next, we highlight recent advances in molecular genetics and their potential applications in refining HCM diagnosis, risk stratification, and treatment. We delve into emerging therapies, such as gene editing, RNA-based therapies, targeted small molecules, and cardiac myosin modulators like mavacamten and aficamten, which hold promise in modulating the underlying molecular mechanisms of HCM. Mavacamten and aficamten, selective modulators of cardiac myosin, have demonstrated encouraging results in clinical trials by reducing left ventricular outflow tract obstruction and improving symptoms in patients with obstructive HCM. We discuss their mechanisms of action, clinical trial outcomes, and potential implications for the future of HCM management. Furthermore, we examine the role of precision medicine in HCM management, exploring how individualised treatment strategies, including exercise prescription as part of the management plan, may optimise patient outcomes. Finally, we underscore the importance of multidisciplinary care and patient-centred approaches to address the complex needs of HCM patients. This review also aims to encourage further research and collaboration in the field of HCM, promoting the development of novel and more effective therapeutic strategies, such as cardiac myosin modulators, to hopefully improve the quality of life and outcome of patients with sarcomeric HCM.

Interchangeability in Left Ventricular Ejection Fraction Measured by Echocardiography and cardiovascular Magnetic Resonance: Not a Perfect Match in the Real World.

Comparisons of transthoracic echocardiography (TTE) and cardiovascular magnetic resonance (CMR) derived left ventricular ejection fraction (LVEF) have been reported in core-lab settings but are limited in the real-world setting. We retrospectively identified outpatients from 4 hospital sites who had clinically indicated quantitative assessment of LVEFTTE and LVEFCMR and evaluated their concordance. In 767 patients (mean age 47.6 years; 67.9% males) the median inter-modality interval was 35 days. There was significant positive correlation between the 2 modalities (r = 0.75; P < 0.001). Median LVEF was 54% (IQR 47%, 60%) for TTE and 59% (IQR 51%, 64%) for CMR, (P < 0.001). Normal LVEFTTE was confirmed by CMR in 90.6% of cases. Of patients with severely impaired LVEFTTE, 42.3% were upwardly reclassified by CMR as less severely impaired. The overall proportion of patients that had their LVEF category confirmed by both imaging modalities was 64.4%; Cohen's Kappa 0.41, indicating fair-to-moderate agreement. Overall, CMR upwardly reclassified 28% of patients using the British Society of Echocardiography LVEF grading, 18.6% using the European Society of Cardiology heart failure classification, and 29.6% using specific reference ranges for each modality. In a multi-site "real-worldˮ clinical setting, there was significant discrepancy between LVEFTTE and LVEFCMR measurement. Only 64.4% had their LVEF category confirmed by both imaging modalities. LVEFTTE was generally lower than LVEFCMR. LVEFCMR upwardly reclassified almost half of patients with severe LV dysfunction by LVEFTTE. Clinicians should consider the inter-modality variation before making therapeutic recommendations, particularly as clinical trial LVEF thresholds have historically been guided by echocardiography.

Cardiovascular Morbidity and Mortality Related to Non-alcoholic Fatty Liver Disease: A Systematic Review and Meta-analysis.

Whether non-alcoholic fatty liver disease (NAFLD) is a cardiovascular (CV) risk factor is debated. We performed a systematic review and meta-analysis to assess the CV morbidity and mortality related to NAFLD in the general population, and to determine whether CV risk is comparable between lean and non-lean NAFLD phenotypes. We searched multiple databases, including PubMed, Embase, and the Cochrane Library, for observational studies published through 2022 that reported the risk of CV events and mortality. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) for all-cause mortality, CV mortality, myocardial infarction (MI), stroke, atrial fibrillation (AF), and major adverse cardiovascular and cerebrovascular events (MACCE) were assessed through random-effect meta-analysis. We identified 33 studies and a total study population of 10,592,851 individuals (mean age 53±8; male sex 50%; NAFLD 2, 9%). Mean follow-up was 10±6 years. Pooled ORs for all-cause and CV mortality were respectively 1.14 (95% CI, 0.78-1.67) and 1.13 (95% CI, 0.57-2.23), indicating no significant association between NAFLD and mortality. NAFLD was associated with increased risk of MI (OR 1.6; 95% CI, 1.5-1.7), stroke (OR: 1.6; 95% CI, 1.2-2.1), atrial fibrillation (OR: 1.7; 95% CI, 1.2-2.3), and MACCE (OR: 2.3; 95% CI, 1.3-4.2). Compared with non-lean NAFLD, lean NAFLD was associated with increased CV mortality (OR: 1.50; 95% CI, 1.1-2.0), but similar all-cause mortality and risk of MACCE. While NAFLD may not be a risk factor for total and CV mortality, it is associated with excess risk of non-fatal CV events. Lean and non-lean NAFLD phenotypes exhibit distinct prognostic profiles and should receive equitable clinical care.

Stalactites in the Right Ventricle.

Heart metastatic tumors are more frequent than primary heart tumors. Cardiac metastasis is a rare phenomenon, occurring mainly by direct spread, especially from lung cancer. Cardiac metastases may be asymptomatic or cause arrhythmias, nonspecific electrocardiographic alterations, or mimic a myocardial infarction. In this case report, we illustrate a rare case of pulmonary adenocarcinoma, which through the bloodstream developed a stalactite-shaped metastasis within the right ventricle of conspicuous size (20 mm × 34 mm × 12 mm). In addition, the tumor compressed the right pulmonary trunk, causing pulmonary hypertension. It is essential to characterize metastasis with multimodality imaging. Such lesions within the right cavities can cause massive pulmonary embolism, as in our case, leading to the patient's death, thrombolytic therapy not being effective.