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Background: The feasibility of spironolactone withdrawal in dilated cardiomyopathy patients with improved ejection fraction remains unknown. This study sought to determine whether spironolactone can be withdrawn safely in this circumstance.Methods: Consecutive patients with idiopathic dilated cardiomyopathy and prescribed spironolactone at discharge were included in this prospective, observational cohort using the Risk Evaluation and Management in Heart Failure Trial (NCT02998788) database. Those patients who experienced an absolute left ventricular ejection fraction (LVEF) improvement ≥10% and a second measurement of LVEF >40% would choose whether to continue spironolactone therapy and be included in final analysis. The primary endpoint was dilated cardiomyopathy relapse within 12 months, defined as a more than 10% reduction in LVEF, a 15% or greater increase in LVESVi, a 2-fold rise in NT-proBNP, or clinical signs of heart failure.Results: Seventy patients achieved an ejection fraction improvement and were included in the final analysis, of whom 30 chose to continue spironolactone and 40 decided to withdraw. In primary endpoint analysis, 23 (58%) patients from the withdrawal group and 4 (13%) patients from the continuation group relapsed (relative risk for relapse: 4.31; 95% CI: 1.67–11.11; p < 0.001). Patients from the withdrawal group experienced more symptom aggravation than the continuation group. No secondary safety endpoint was recorded. Improvements in cardiac structure parameters were no longer observed after spironolactone withdrawal, while improvements persisted in continuation group.Conclusions: Most dilated cardiomyopathy patients with improved ejection fraction will relapse after spironolactone withdrawal. These results should be weighed before spironolactone withdrawal was attempted.

Myocardial fibrosis and ventricular remodeling were the key pathology factors causing undesirable consequence after myocardial infarction. However, an efficient therapeutic method remains unclear, partly due to difficulty in continuously preventing neurohormonal overactivation and potential disadvantages of cell therapy for clinical practice. In this study, a rhACE2-electrospun fibrous patch with sustained releasing of rhACE2 to shape an induction transformation niche in situ was introduced, through micro-sol electrospinning technologies. A durable releasing pattern of rhACE2 encapsulated in hyaluronic acid (HA)—poly(L-lactic acid) (PLLA) core-shell structure was observed. By multiple in vitro studies, the rhACE2 patch demonstrated effectiveness in reducing cardiomyocytes apoptosis under hypoxia stress and inhibiting cardiac fibroblasts proliferation, which gave evidence for its in vivo efficacy. For striking mice myocardial infarction experiments, a successful prevention of adverse ventricular remodeling has been demonstrated, reflecting by improved ejection fraction, normal ventricle structure and less fibrosis. The rhACE2 patch niche showed clear superiority in long term function and structure preservation after ischemia compared with intramyocardial injection. Thus, the micro-sol electrospun rhACE2 fibrous patch niche was proved to be efficient, cost-effective and easy-to-use in preventing ventricular adverse remodeling.

Coronary artery disease (CAD) and associated comorbidities such as heart failure (HF) remain the leading cause of morbidity and mortality worldwide attributed to, at least partially, the lack of biomarkers for efficient disease diagnosis. Here, we evaluated the diagnostic potential of serum peptidoglycan recognition protein 1 (PGLYRP1), an important component of the innate immunity and inflammation system, for both CAD and HF. A machine-learning method (random forest) was used to evaluate the clinical utility of circulating PGLYRP1 for diagnosis of CAD and HF in a total of 370 individuals. Causal links of chronic serum PGLYRP1 elevation to both diseases were further explored in ApoE 2/2 mice. The serum levels of PGLYRP1 were significantly higher in individuals with either chronic CAD or acute coronary syndrome than those in those without coronary artery stenosis (the control group) and even more pronounced in CAD individuals with concomitant HF. Our random forest classifier revealed that this protein performed better than other recommended clinical indicators in distinguishing the CAD from the control individuals. In addition, this protein associates more with the biomarkers of HF including left ventricular ejection fraction than inflammation. Notably, our mice experiment indicated that longterm treatment with recombinant PGLYRP1 could significantly impair the cardiovascular system as reflected from both increased atherogenic lesions and reduced fractional shortening of the left ventricle. Our findings, therefore, supported the circulating levels of PGLYRP1 as a valuable biomarker for both CAD and HF.

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This study aimed to identify microbial signatures that contribute to the shared etiologies between chronic heart failure (CHF), type 2 diabetes, and chronic kidney disease. The serum levels of 151 microbial metabolites were measured in 260 individuals from the Risk Evaluation and Management of heart failure cohort, and it was found that those metabolites varied by an order of 10 5 fold. Out of 96 metabolites associated with the three cardiometabolic diseases, most were validated in two geographically independent cohorts. In all three cohorts, 16 metabolites including imidazole propionate (ImP) consistently showed significant differences. Notably, baseline ImP levels were three times higher in the Chinese compared with the Swedish cohorts and increased by 1.1-1.6 fold with each additional CHF comorbidity in the Chinese population. Cellular experiments further supported a causal link between ImP and distinct CHF relevant phenotypes. Additionally, key microbial metabolite-based risk scores were superior in CHF prognosis than the traditional Framingham or Get with the Guidelines-Heart Failure risk scores. Interactive visualization of these specific metabolite-disease links is available on our omics data server (https://omicsdata.org/Apps/REM-HF/).

Introduction Lung cancer is a major global health problem because of its high incidence and mortality. Targeted therapies have transformed treatment of driver-mutated metastatic non-small cell lung cancer (NSCLC). Nevertheless, recent studies demonstrated that cardiovascular disease (CVD) was the second leading cause of mortality in cancer survivors now, management of patients’ cardiovascular health during the course of anticancer therapy has become a great challenge faced by the oncologists. Anticancer related cardiovascular (CV) complications are not limited to traditional chemotherapy, but are also increasingly recognized in targeted therapy. Case Report We present a case of pulmonary embolism (PE) and bradycardia in a 91-year-old NSCLC patient treated with crizotinib for a rare MET Y1003S mutation. To our knowledge, this is the second report to show antitumor response of crizotinib in lung cancer patients with such a rare mutation. However, the patient complained chest tightness and shortness of breath after a month of standard dose crizotinib therapy. Non-invasive examination revealed new onset bradycardia and PE. Management & Outcome Such clinical manifestations were associated with targeted therapy-related CV toxicity, on which the emerging discipline cardio-oncology focused, and a multidisciplinary investigation and treatment was conducted. Discussion This case highlights the CV adverse events of novel therapies and the current challenges to be tackled in cardio-oncology.

Background Insulin resistance is an overlapping risk factor for both heart and breast cancer, while its interaction with cardiotoxicity in breast cancer (BC) patients is not clear. This study investigated the impact of insulin resistance on cardiac remodeling in patients with human epidermal growth factor receptor 2 (HER2)-positive BC during and after trastuzumab therapy in real-world clinical practice. Methods HER2-positive BC patients who received trastuzumab treatment between December 2012 and December 2017 were reviewed and 441 patients with baseline metabolic indices and serial echocardiographic measurements (baseline, 6, 12, and 18 months) after trastuzumab therapy initiation were included. Repeated measurement analysis of variance was used to evaluate temporal trends in multiparameter echocardiography. Linear mixed model was applied to further evaluate the role of insulin resistance in forementioned changes. Correlation of homeostasis model assessment-estimated insulin resistance (HOMA-IR) and triglyceride-glucose index (TyG) levels to changes in echocardiography parameters was explored. Results Of 441 patients (mean age 54 ± 10 [SD] years), 61.8% received anthracycline-based chemotherapy, 33.5% received left-sided radiotherapy, 46% received endocrine therapy. No symptomatic cardiac dysfunction was observed over the therapy course. A total of 19 (4.3%) participants experienced asymptomatic cancer therapy-related cardiac dysfunction (CTRCD), and the peak onset time was 12 months after the initiation of trastuzumab. Albeit relatively low CTRCD incidence, cardiac geometry remodeling, especially left atrial (LA) dilation over therapy was notable and was more severe in high HOMA-IR and TyG level groups (P < 0.01). Noteworthy, a partial reversibility of cardiac remodeling was observed with treatment cessation. Additionally, HOMA-IR level positively correlated to changes in LA diameter from baseline to 12 months (r = 0.178, P = 0.003). No significant association (all P > 0.10) was detected between HOMA-IR or TyG level and dynamic left ventricular parameter evaluation. Multivariate linear regression analysis demonstrated that higher HOMA-IR level was an independent determinant for LA enlargement in BC patients during anti-HER2 targeted therapy course after adjusting for confounding risk factors (P = 0.006). Conclusion Insulin resistance was associated with left atrial adverse remodeling (LAAR) in HER2-positive BC patients that received standard trastuzumab therapy, indicating that insulin resistance could be a supplementation to baseline cardiovascular risk stratification proforma for HER2-targeted antitumor therapies.