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Background: Patients with heart failure with reduced ejection fraction (HFrEF) and central sleep apnea (CSA) are at a very high risk of fatal outcomes., Objective: To test whether the circulating miRNome provides additional information for risk stratification on top of clinical predictors in patients with HFrEF and CSA., Methods: The study included patients with HFrEF and CSA from the SERVE-HF trial. A three-step protocol was applied: microRNA (miRNA) screening (n = 20), technical validation (n = 60), and biological validation (n = 587). The primary outcome was either death from any cause, lifesaving cardiovascular intervention, or unplanned hospitalization for worsening of heart failure, whatever occurred first. MiRNA quantification was performed in plasma samples using miRNA sequencing and RT-qPCR., Results: Circulating miR-133a-3p levels were inversely associated with the primary study outcome. Nonetheless, miR-133a-3p did not improve a previously established clinical prognostic model in terms of discrimination or reclassification. A customized regression tree model constructed using the Classification and Regression Tree (CART) algorithm identified eight patient subphenotypes with specific risk patterns based on clinical and molecular characteristics. MiR-133a-3p entered the regression tree defining the group at the lowest risk; patients with log(NT-proBNP) ≤ 6 pg/mL (miR-133a-3p levels above 1.5 arbitrary units). The overall predictive capacity of suffering the event was highly stable over the follow-up (from 0.735 to 0.767)., Conclusions: The combination of clinical information, circulating miRNAs, and decision tree learning allows the identification of specific risk subphenotypes in patients with HFrEF and CSA., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Heart failure (HF) is a global challenge, with lower- and middle-income countries (LMICs) carrying a large share of the burden. Treatment for HF with reduced ejection fraction (HFrEF) improves survival but is often underused. Economic factors might have an important effect on the use of medicines., Methods and Results: This analysis assessed prescription rates and doses of renin-angiotensin system (RAS) inhibitors, β-blockers, and mineralocorticoid receptor antagonists at discharge and 6-month follow-up in 8669 patients with HFrEF (1458 from low-, 3363 from middle-, and 3848 from high-income countries) hospitalized for acute HF in 44 countries in the prospective REPORT-HF study. We investigated determinants of guideline-recommended treatments and their association with 1-year mortality, correcting for treatment indication bias.Only 37% of patients at discharge and 34% of survivors at 6 months were on all three medication classes, with lower proportions in LMICs than high-income countries (19 vs. 41% at discharge and 15 vs. 37% at 6 months). Women and patients without health insurance, or from LMICs, or without a scheduled medical follow-up within 6 months of discharge were least likely to be on guideline-recommended medical therapy at target doses, independent of confounders. Being on ≥50% of guideline-recommended doses of RAS inhibitors, and β-blockers were independently associated with better 1-year survival, regardless of country income level., Conclusion: Patients with HFrEF in LMICs are less likely to receive guideline-recommended drugs at target doses. Improved access to medications and medical care could reduce international disparities in outcome., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The left ventricular ejection fraction (LVEF) is the most commonly used measure describing pumping efficiency, but it is heavily dependent on loading conditions and therefore not well-suited to study pathophysiologic changes. The novel concept of echocardiography-derived myocardial work (MyW) overcomes this disadvantage as it is based on LV pressure-strain loops. We tracked the in-hospital changes of indices of MyW in patients admitted for acute heart failure (AHF) in relation to their recompensation status and explored the prognostic utility of MyW indices METHODS AND RESULTS: We studied 126 patients admitted for AHF (mean 73 ± 12 years, 37% female, 40% with a reduced LVEF [<40%]), providing pairs of echocardiograms obtained both on hospital admission and prior to discharge. The following MyW indices were derived: global constructive and wasted work (GCW, GWW), global work index (GWI), and global work efficiency. In patients with HF with reduced ejection fraction with decreasing N-terminal prohormone B-natriuretic peptide levels during hospitalization, the GCW and GWI improved significantly, whereas the GWW remained unchanged. In patients with HF with preserved ejection fraction, the GCW and GWI were unchanged; however, in patients with no decrease or eventual increase in N-terminal prohormone B-natriuretic peptide, we observed an increase in GWW. In all patients with AHF, higher values of GWW were associated with a higher risk of death or rehospitalization within 6 months after discharge (per 10-point increment hazard ratio 1.035, 95% confidence interval 1.005-1.065)., Conclusions: Our results suggest differential myocardial responses to decompensation and recompensation, depending on the HF phenotype in patients presenting with AHF. The GWW predicted the 6-month prognosis in these patients, regardless of LVEF. Future studies in larger cohorts need to confirm our results and identify determinants of short-term and longer term changes in MyW., Competing Interests: Declaration of Competing Interest Floran Sahiti receives financial support from IZKF Würzburg (MD/PhD program scholarship). Caroline Morbach reports a research cooperation with the University of Würzburg and Tomtec Imaging Systems funded by a research grant from the Bavarian Ministry of Economic Affairs, Regional Development and Energy, Germany, speakers honorarium from Amgen and Tomtec, a travel grant from Orion Pharma and Alnylam, and participation in Advisory and Patient Eligibility Boards sponsored by AKCEA, Alnylam, Pfizer, and EBR Systems outside the submitted work. Carsten Henneges has nothing to disclose. Ulrich Stefenelli has nothing to disclose. Nina Scholz has nothing to disclose. Vladimir Cejka has nothing to disclose. Judith Albert has nothing to disclose. Peter U. Heuschmann reports grants from the German Ministry of Research and Education, European Union, Charité – Universitätsmedizin Berlin, Berlin Chamber of Physicians, German Parkinson Society, University Hospital Würzburg, Robert Koch Institute, German Heart Foundation, Federal Joint Committee (G-BA) within the Innovationfond, University Hospital Heidelberg (within RASUNOA-prime; RASUNOA-prime is supported by an unrestricted research grant to the University Hospital Heidelberg from Bayer, BMS, Boehringer-Ingelheim, Daiichi Sankyo), grants from Charité – Universitätsmedizin Berlin (within Mondafis; Mondafis is supported by an unrestricted research grant to the Charité from Bayer), from University Göttingen (within FIND-AF randomized; FIND-AF randomized is supported by an unrestricted research grant to the University Göttingen from Boehringer Ingelheim), outside the submitted work. Georg Ertl reports significant honoraria for trial leadership from Abbott, and Novartis; has been a consultant for Abbott, Boehringer Ingelheim, Novartis, ResMed, and Vifor (modest); and received significant grant support from Boehringer Ingelheim, Thermo Fisher, Siemens Healthineers, Vifor, and Federal Ministry of Education and Research. Stefan Frantz reports research grants from the German Ministry of Education and Research. He received honoraria from and was on advisory boards for AMGEN Europe, AstraZeneca, Bayer Vital, Boehringer Ingelheim, Bristol-Meyers Squibb GmbH, Daiichi Sankyo, MSD, Novartis, Pfizer, Sanofi, Servier, Vifor. Christiane Angermann reports honoraria for trial leadership from Abbott, Boehringer Ingelheim, and Novartis; has been a consultant for Abbott, Boehringer Ingelheim, Novartis, ResMed, Springer, and Vifor; and received significant grant support from Boehringer Ingelheim, Thermo Fisher, Siemens Healthineers, Vifor, Competence Network Heart Failure, Würzburg, and the Federal Ministry of Education and Research. Stefan Störk reports research grants from the German Ministry of Education and Research, European Union, University Hospital Würzburg; participation in Data Safety Monitoring or Event Adjudication in studies sponsored by Roche and Medtronic; participated on Advisory Boards for Novartis, Bayer, Boehringer Ingelheim, Thermo-Fisher, and Boston Scientific; principal investigator in trials (co-) sponsored by Boehringer Ingelheim, Novartis, and Bayer; and received speaker honoraria from Boehringer Ingelheim, Servier, Novartis, Astra-Zeneca, Pfizer, Bayer, and Thermo-Fisher, outside the submitted work., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Heart failure remains a frequent cause of death and is the leading reason for hospitalization in Germany although therapeutic options have significantly increased over the past years particularly in heart failure with reduced ejection fraction. Clinical symptoms are usually preceded by cardiac remodeling, which was originally defined only by left ventricular dilatation and depressed function but is also associated with typical cellular and molecular processes. Healing after acute myocardial infarction is characterized by inflammation, cellular migration and scar formation. Cardiac remodeling is accompanied by adaptive changes of the peripheral cardiovascular system. Since prevention is the primary goal, rapid diagnosis and treatment of myocardial infarction are mandatory. Early reperfusion therapy limits infarct size and enables the best possible preservation of left ventricular function. Standard pharmacotherapy includes angiotensin-converting enzyme inhibitors, angiotensin-1-receptor blockers and beta blockers. In addition, mineralocorticoid receptor antagonists have proven beneficial. Compounds specifically targeting infarct healing processes are currently under development.

Background: Peripartum cardiomyopathy (PPCM) is an idiopathic heart disease that develops in the last month of pregnancy and/or the first months following delivery in previously healthy women and may lead to acute heart failure. A cleaved fragment of the nursing hormone prolactin is considered essential in the pathophysiology of PPCM. To date, no specific therapy has been tested for PPCM in a randomized controlled trial of adequate size., Aims: The purpose of this trial is to investigate the safety of the dopamin-D2-receptor agonist bromocriptine and its effects on left ventricular (LV) function in women with PPCM., Methods: This is an 11 center German trial with a prospective randomized controlled open-label design. The trial enrolls females with newly diagnosed PPCM according to European Society of Cardiology criteria with a LV ejection fraction (LVEF) <35 %. Patients are randomized 1:1 to either best supportive care (BSC) including standard heart failure therapy plus 8 weeks of bromocriptine therapy (2.5 mg b.i.d. for 14 days and 2.5 mg q.d. from day 15 to 56) or to BSC plus 1 week of low-dose bromocriptine (2.5 mg q.d.) with anticoagulant therapy at a prophylactic dose administered during the period of bromocriptine treatment in both groups. The primary endpoint is change in LVEF from baseline to 6 months follow-up as assessed by cardiac magnetic resonance imaging (or echocardiography if CMR is not tolerated). The secondary endpoints are hospitalization for worsening heart failure, heart transplantation, and all-cause mortality during follow-up or a combination of these endpoints. A total of 60 patients will be recruited (including 6 potential dropouts) giving a power of 0.9 for an expected LVEF change of 10.8 % between treatment groups at 6 months., Perspective: This trial will provide important knowledge on potential benefits and safety of prolonged inhibition of prolactin release with bromocriptine in addition to standard heart failure therapy in newly diagnosed PPCM., Trial Registration: ClinicalTrials.gov Identifier: NCT00998556.

Background: To assess heart failure therapies in diabetic patients with preserved as compared to impaired systolic ventricular function., Methods: 3304 patients with heart failure from 9 different studies were included (mean age 63 ± 14 years); out of these, 711 subjects had preserved left ventricular ejection fraction (≥ 50%) and 994 patients in the whole cohort suffered from diabetes., Results: The majority (>90%) of heart failure patients with reduced ejection fraction (SHF) and diabetes were treated with an ACE inhibitor (ACEi) or angiotensin receptor blocker (ARB) or with beta-blockers. By contrast, patients with diabetes and preserved ejection fraction (HFNEF) were less likely to receive these substance classes (p < 0.001) and had a worse blood pressure control (p < 0.001). In comparison to patients without diabetes, the probability to receive these therapies was increased in diabetic HFNEF patients (p < 0.001), but not in diabetic SHF patients. Aldosterone receptor blockers were given more often to diabetic patients with reduced ejection fraction (p < 0.001), and the presence and severity of diabetes decreased the probability to receive this substance class, irrespective of renal function., Conclusions: Diabetic patients with HFNEF received less heart failure medication and showed a poorer control of blood pressure as compared to diabetic patients with SHF. SHF patients with diabetes were less likely to receive aldosterone receptor blocker therapy, irrespective of renal function.

Objective: To study the association of circulating markers of fibrosis: procollagen type III amino-terminal propeptide (PIIINP), procollagen type I carboxy-terminal propeptide (PIP) and collagen type I carboxy-terminal telopeptide (CITP): with left (LV) and right ventricular (RV) longitudinal and LV radial systolic function in patients with heart failure in the course of essential hypertension., Methods: The study population consisted of 81 patients with hypertension divided into four groups according to NYHA classification and 20 healthy controls. Cardiac function was estimated by myocardial deformation indices assessed by tissue Doppler imaging. Serum PIIINP, PIP and CITP levels were quantified by radioimmunoassay., Results: Progressive LV longitudinal function impairment was demonstrated in all hypertension groups as indicated by reduced peak systolic strain and strain rate and increased postsystolic strain index. The respective indicators of LV radial function were deteriorated only in NYHA classes III-IV. Concurrently, RV longitudinal function was found abnormal in NYHA classes II-IV. PIIINP concentration was higher in NYHA class III and IV, whereas CITP level was increased and PIP/CITP ratio was decreased in the NYHA IV individuals. PIIINP was an independent correlate of LV and RV longitudinal strain (R = 0.52, beta = -0.34, P < 0.001; R = 0.25, beta = -0.27, P < 0.01, respectively). PIP/CITP ratio independently determined LV radial strain in patients with LV ejection fraction less than 50% (R = 0.44, beta = 0.52, P < 0.008)., Conclusion: In hypertensive patients, the progressive decline in cardiac longitudinal function is related to increased collagen III synthesis, whereas the changes in collagen I turnover favoring its increased degradation might contribute to LV radial and global systolic dysfunction seen in the advanced hypertensive heart disease.

Rising prevalence and disease-related costs render chronic heart failure a rapidly growing socioeconomic challenge. Guideline-adjusted diagnosis and appropriate therapy are successful in improving mortality, morbidity, functional status and quality of life of patients with chronic left ventricular failure. Corresponding state-of-art recommendations were recently published in the updated European and American treatment guidelines. They determine a stepwise escalation of pharmacological and surgical treatment measures according to increasing disease severity. Still, the complexity of the heart failure syndrome demands to tailor diagnostic procedures and therapy to the patients' individual needs and circumstances.

Objective: Two-dimensional (2-D) strain imaging is a novel echocardiographic technique for myocardial function evaluation. We sought to investigate left ventricular (LV) systolic function in patients with heart failure caused by hypertension using a 2-D strain approach and to validate this method against Doppler strain measurements., Methods: The study population comprised 81 patients (66.4 +/- 7.4 years) with hypertension in New York Heart Association (NYHA) class I to IV and 20 healthy controls., Results: Decreased longitudinal strain was demonstrated in the basal septal segment in NYHA I, in the basal and mid septal and basal lateral segments in NYHA II, and in all segments in NYHA III and IV. Radial and circumferential strain were reduced in patients with NYHA III and IV. Independent predictors of strain were duration of HT, LV mass index, LV end-diastolic volume index, and systolic blood pressure. The agreement between 2-D and Doppler strain remained within acceptable ranges (mean difference +/- 1 standard deviation: 0.61%-1.92% +/- 2.38%-2.92% for longitudinal strain in particular segments and 4.98% +/- 5.26% for radial strain)., Conclusion: In hypertensive patients, (1) LV longitudinal systolic function progressively deteriorates from NYHA I to IV and abnormalities commence in the basal septum, (2) LV radial and circumferential systolic impairment appears in NYHA III and IV, and (3) 2-D strain measurement provides a feasible tool for the quantitation of LV systolic performance.

Background: Statins reduce cardiomyocyte hypertrophy in animal models of hypertrophic cardiomyopathy, aortic banding and heart failure after myocardial infarction. We investigated the effect of the hydroxymethylglutaryl coenzyme A reductase inhibitor atorvastatin on left ventricular (LV) mass in patients with hypertrophic cardiomyopathy in a randomized placebo-controlled double-blind pilot study., Materials and Methods: Patients with hypertrophic cardiomyopathy were randomized to be treated once daily by atorvastatin 80 mg or placebo for nine months. LV mass was assessed by serial cardiac magnetic resonance imaging. LV systolic and diastolic function was determined by echocardiography. Markers of collagen metabolism and inflammation were also assessed., Results: Out of 78 screened patients with hypertrophic cardiomyopathy 28 (2 x 14) patients were eligible for randomization. Eleven patients in each group completed the study with cardiac magnetic resonance imaging assessments meeting the evaluation standards at baseline and at follow-up. Low-density lipoprotein cholesterol levels in the atorvastatin group decreased from 3.24 +/- 1.14 mmol L(-1) (125 +/- 44 mg dL(-1)) at baseline to 1.37 +/- 0.49 mmol L(-1) (53 +/- 19 mg dL(-1)) at follow-up (P < 0.001), but were unchanged in the placebo group. Baseline LV mass was 228 +/- 51 g in the placebo and 232 +/- 67 g in the atorvastatin group. The primary endpoint of change in LV mass from baseline to follow-up was 2 +/- 10% in the atorvastatin group versus 0 +/- 13% in the placebo group (P = NS). Parameters of LV volumes and diameters, systolic and diastolic function, and markers of collagen metabolism were also unchanged in both groups., Conclusion: In patients with hypertrophic cardiomyopathy, this randomized placebo-controlled double-blind pilot study did not demonstrate an effect of 9-month treatment with atorvastatin 80 mg on LV mass reduction.

Aims: The present study aims to compare the change of left ventricular deformation during dobutamine stress echocardiography (DSE) with the reference standard of invasive myocardial fractional flow reserve (FFR) to assess the haemodynamic significance of intermediate coronary lesions., Methods and Results: In 30 patients with an intermediate coronary artery stenosis in one epicardial coronary artery, FFR measurements were performed during coronary catheterization. In case of an FFR < 0.75 after intracoronary adenosine administration, the stenosis was considered significant, indicating ischaemia. In addition, during DSE, peak systolic strain rate and systolic strain of the region of interest (supplied by the stenotic vessel) and of a non-ischaemic remote region were assessed at baseline and at peak stress. Thirteen patients had an FFR >or= 0.75, indicating normal flow reserve (non-ischaemic group). The remaining 17 patients with an FFR < 0.75 comprised the ischaemic group. At baseline DSE, mean values of strain rate (-1.2 +/- 0.3 s(-1)) and strain (-17 +/- 8%) were not significantly different between both groups. In the ischaemic group, in the target region, strain at peak stress decreased to - 10 +/- 8%, whereas strain rate remained unchanged. In contrast, in the non-ischaemic group, strain at peak stress remained unchanged (-18 +/- 7%), whereas strain rate increased to - 2.5 +/- 1.1 s(-1). The receiver operating characteristic curve analysis revealed the change in strain rate as the best parameter to detect ischaemia, with a sensitivity of 89% and a specificity of 86%. In the remote region, in both groups, strain rate (-1.4 +/- 0.4 s(-1)) and strain values (-20 +/- 7%) were not significantly different at baseline, and strain rate doubled and strain remained unchanged at DSE peak stress., Conclusion: Non-invasive evaluation of regional deformation, using strain rate imaging during DSE, predicted the relevance of intermediate coronary stenosis. In this context, strain rate is superior to strain measurements for the quantification of the contractile reserve.

Chronic heart failure is an increasingly frequent clinical syndrome, characterized by reduced physical performance, dyspnea and an adverse prognosis. It is associated with age, indicating that it will become more common. Diagnosis requires the characterization of cardiac dysfunction and a precise definition of the underlying cardiac disease. Treatment guidelines of the cardiac societies, which were updated 2005, recommend therapy with ACE-inhibitors, AT1 receptor antagonists, beta-blockers, aldosterone antagonists and digitalis. It is essential, however, to consider the individual circumstances such as underlying disease, age as well as the frequent complications and comorbidities.