Explore the vast range of titles available.

The optimal timing of aortic valve replacement in asymptomatic patients with aortic stenosis is uncertain. Replacement fibrosis, as assessed by midwall (nonischemic) late gadolinium enhancement (LGE) on cardiac magnetic resonance (CMR) imaging, is an irreversible marker of left ventricular decompensation in aortic stenosis. Once established, it progresses rapidly and is associated with poor long-term prognosis in a dose-dependent manner. The objective of this multicenter prospective randomized controlled trial is to determine whether early aortic valve replacement in asymptomatic patients with severe aortic stenosis can improve the adverse prognosis associated with midwall LGE. Patients will be screened for likelihood of having LGE with electrocardiography or high-sensitivity troponin I. Those at high risk will proceed to CMR imaging. Approximately 400 patients with midwall LGE will be randomized 1:1 to early valve replacement or routine care. Those who do not exhibit midwall LGE will continue with routine care and be randomized to a study registry or no further follow-up. Follow-up will be annual for approximately 3 years until the number of required outcome events is achieved. The primary endpoint is a composite of all-cause mortality and unplanned aortic stenosis–related hospitalization. The expected event rate is 25.0% in the routine care arm and 13.4% in the early intervention arm over the first 2 years; 88 observed primary outcome events will give 90% power at 5% significance level. Key secondary endpoints include all-cause mortality, sudden cardiac death, stroke, and symptomatic status. The EVOLVED trial is the first multicenter randomized controlled trial to compare early aortic valve replacement to routine care in asymptomatic patients with severe aortic stenosis and midwall LGE.

Introduction Arrhythmia‐induced cardiomyopathy (AIC) is an underrecognized condition resulting in left ventricular systolic dysfunction (LVSD) that is primarily caused by atrial fibrillation (AFib). The relationship between AIC, right ventricular (RV) function, and quality of life (QoL) has not been well studied. Methods We performed a post‐hoc analysis of our AIC trial in which we prospectively screened for patients with tachyarrhythmia and newly diagnosed, otherwise unexplained LVSD. Following rhythm restoration, patients were followed up at 2, 4, and 6 months. Only patients with persistent sinus rhythm were analyzed. RV function was assessed via echocardiography (tricuspid annular plane systolic excursion [TASPE] and fractional area change [FAC]) and QoL by the Minnesota Living with Heart Failure Questionnaire. Results Of a total of 50 patients recovering from LVSD, 41 were diagnosed with AIC and 9 with non‐AIC. Initially, RV function was reduced in the AIC group and recovered after rhythm restoration, whereas no relevant changes were noted in the non‐AIC group. QoL was reduced in both groups and also improved after rhythm restoration. Regression analysis identified low TAPSE as a predictive parameter for AIC diagnosis and worse QoL in AIC patients. Conclusion We demonstrated that RV function and QoL are impaired in patients with AIC. Six months after rhythm restoration, TAPSE may serve as an early indicator of AIC while also correlating with QoL. This underscores the importance of detailed echocardiographic evaluation with a focus on RV function in patients with concomitant tachyarrhythmia and LVSD. Initial tricuspid annular plane systolic excursion (TAPSE), quality of life (QoL) as measured by the Minnesota Living with Heart Failure Questionnaire and left ventricular ejection fraction (LVEF) during atrial fibrillation (AFib) or atrial flutter (AFlut) were reduced in patients with arrhythmia‐induced cardiomyopathy (AIC) compared with values at the end of 6 months of follow‐up in sinus rhythm. In this paper we show that low TAPSE (optimal cut‐off 18.5 mm) has good predictive power for the diagnosis of AIC and that a low quality of life is associated with low TAPSE. Values in red indicate the relative percent the baseline values were reduced compared with the post‐recovery measurement at the end of follow‐up.

PurposeTo investigate the impact of soccer training on cardiac adaptations in mildly hypertensive middle-aged women.MethodsHypertensive premenopausal women (n = 41; age (mean ± SD): 44 ± 7 years; height: 166 ± 6 cm; weight: 78.6 ± 11.6 kg; body fat: 43.3 ± 5.2%) were randomized to soccer training (SOC, n = 21) or control (CON, n = 20). SOC performed three weekly training sessions for 15 weeks, whereas CON had no training or lifestyle changes during the same period. Cardiac structure and function were assessed by echocardiography pre-intervention and post-intervention.ResultsSoccer training increased (P = 0.001) left ventricular mass index by 10% [95% CI 4; 15], while no changes occurred in CON (time × group interaction, P = 0.005). In addition, only SOC demonstrated a within-group increase (P = 0.01) of 8% [95% CI 2; 14] in left ventricular septum diameter. For markers of right ventricular remodelling, a within-group increase (P = 0.02) occurred for tricuspid annulus plane systolic excursion of 8% [95% CI 1; 14] in SOC only. Left atrial diameter index increased (P < 0.001) by 6% [95% CI 3; 10] after SOC, while it was unaffected in CON (time × group interaction, P = 0.02). For makers of diastolic function, SOC demonstrated a within-group increase (P = 0.02) in the average early diastolic mitral annulus velocity of 10% [95% CI 2; 19]. In addition, a reduction (P < 0.001) in mitral valve A velocity of − 19% [95% CI − 29; − 10] was observed following soccer training, which manifested in increased (P < 0.001) mitral valve E/A ratio of 34% [95% CI 16; 53] in SOC. No within-group changes were apparent in CON.ConclusionIn sedentary, mildly hypertensive, middle-aged women, 15 weeks of soccer training increases left ventricular mass and left atrial diameter and improves indices of left ventricular diastolic function.

•Cardiovascular aging is associated with myocardial dysfunction, with consequent atrial fibrillation and heart failure.•STAREE-HEART is a clinical trial assessing the effect of atorvastatin compared with placebo on markers of cardiovascular aging in a healthy older population.•A total of 369 participants underwent a comprehensive cardiac evaluation before randomization, which will be repeated at 3 years.•Atorvastatin may provide a population-wide prevention strategy for cardiovascular aging. Statins may prevent myocardial dysfunction associated with aging, and consequent atrial fibrillation (AF) and heart failure (HF). STAREE-HEART is a randomized, double-blind, placebo-controlled clinical trial assessing atorvastatin on markers of cardiovascular aging in a healthy older population. This ancillary study is nested in the STAtins in Reducing Events in the Elderly (STAREE) primary prevention trial. Participants ≥ 70 years (n = 369) have been randomized to atorvastatin or placebo. Assessment at baseline and 3-years includes echocardiogram, electrocardiography and blood collection for biomarker assessment. The primary endpoint is change in global longitudinal strain (GLS), a measure of left ventricular systolic function. An estimated 184 participants per group enables detection of mean GLS at 3 years in the placebo group being 2.0 percentage points lower than mean GLS in the statin group at 3 years, assuming SD = 5 percentage points and a 15% attrition rate, with power >90%. We present summary statistics describing participants at baseline. The mean age of the 369 STAREE-HEART participants was 73.0 years (SD 3.4). Mean left ventricular (LV) ejection fraction was 64.0% (SD 6.1), and mean GLS was 19.2% (SD 2.2). Mean GLS was similar between females and males (19.4% vs 19.0%) and slightly higher in those aged 70 to 74 compared to ≥75 years (19.4% vs 18.6%). AF was detected on screening in 4.5% of participants. The STAREE-HEART ancillary study will provide mechanistic detail concerning myocardial dysfunction and its consequences, to determine if atorvastatin affects left ventricular systolic function associated with aging. clinicaltrials.gov. Unique identifier: NCT04536870.

Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use. This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points. Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183). X = vital status/events (CV death, HF hospitalization, worsening HF), physical examination, blood sampling, urine sampling, HF symptom assessment, KCCQ-23. *Standard HF therapy is continued throughout the study. †At day 45, KCCQ-23 was not administered. At selected sites, samples will be collected in protease inhibitor tubes at each timepoint (n = 180). [Display omitted]

Sacubitril/valsartan (LCZ696) is an angiotensin receptor neprilysin inhibitor approved for the treatment of adult heart failure (HF); however, the benefit of sacubitril/valsartan in pediatric HF patients is unknown. This global multi-center study will use an adaptive, seamless two-part design. Part 1 will assess the pharmacokinetics/pharmacodynamics of single ascending doses of sacubitril/valsartan in pediatric (1 month to <18 years) HF patients with systemic left ventricle and reduced left ventricular systolic function stratified into 3 age groups (Group 1: 6 to <18 years; Group 2: 1 to <6 years; Group 3: 1 month to <1 year). Part 2 is a 52-week, efficacy and safety study where 360 eligible patients will be randomized to sacubitril/valsartan or enalapril. A novel global rank primary endpoint derived by ranking patients (worst-to-best outcome) based on clinical events such as death, initiation of mechanical life support, listing for urgent heart transplant, worsening HF, measures of functional capacity (NYHA/Ross scores), and patient-reported HF symptoms will be used to assess efficacy. The PANORAMA-HF study, which will be the largest prospective pediatric HF trial conducted to date and the first to use a global rank primary endpoint, will determine whether sacubitril/valsartan is superior to enalapril for treatment of pediatric HF patients with reduced systemic left ventricular systolic function. Design of the two-stage, seamless, adaptive PANORAMA-HF study assessing the PK/PD, safety, and efficacy of sacubitril/valsartan versus enalapril in pediatric heart failure patients with systemic left ventricle and reduced left ventricular systolic function. bid, twice-weekly; m, month; mg, milligram; kg, kilogram; PD, pharmacodynamics; PK, pharmacokinetics. [Display omitted]

BackgroundTo determine whether granulocyte colony-stimulating factor (G-CSF) improves clinical outcomes after large ST-elevation myocardial infarction (STEMI) when administered early in patients with left ventricular (LV) dysfunction after successful percutaneous coronary intervention (PCI).MethodsSTEM-AMI OUTCOME was designed as a prospective, multicentre, nationwide, randomised, open-label, phase III trial (ClinicalTrials.gov ID: NCT01969890) to demonstrate the efficacy and safety of early G-CSF administration in reducing 2-year cardiac mortality and morbidity in patients with STEMI with LV ejection fraction ≤45% after PCI. The primary outcome was a composite of all-cause death, recurrence of myocardial infarction and hospitalisation for heart failure. Due to low recruitment and event rates, the study was discontinued and did not achieve adequate statistical power to verify the hypothesis.ResultsPatients were randomly allocated to G-CSF (n=260) or standard of care (SOC; n=261). No difference was found in the composite primary outcome between study groups (HR 1.20; 95% CI 0.63 to 2.28). The 2-year mortality was 2.31% in the G-CSF and 2.68% in the control group (HR 0.88; 95% CI 0.29 to 2.60). Adverse events did not differ between the G-CSF (n=65) and SOC groups (n=58; OR 1.17; 95% CI 0.78 to 1.75). In post hoc analyses on the intervention group, we observed a trend towards fewer composite primary outcomes in patients with low bone marrow (BM) cell mobilisation (n=108) versus those with high mobilisation (n=152, with peak leucocyte count >50×109/L; HR 2.86; 95% CI 0.96 to 8.56). Primary outcomes were lower in patients with severe LV systolic dysfunction at discharge treated with G-CSF than in controls (interaction β±SE, −0.08±0.04; p=0.034).ConclusionsAlthough inconclusive, this is the largest trial in the field of cell-based cardiac repair after STEMI providing evidence of the tolerability and long-term safety of G-CSF treatment. The results prompt further studies to understand which patient can benefit most from BM cell mobilisation.Trial registration number NCT01969890.

Background: Minors are considered the main consumer group of energy drinks (EDs). The aim of this study was to investigate the acute effects of ED consumption on left ventricular (LV) hemodynamics and efficiency in healthy children and teenagers. Methods: This study was a randomized, single-blind, placebo-controlled, crossover clinical trial. Study participants consumed a weight-adjusted amount of an ED or a placebo on two consecutive days. LV hemodynamics and efficiency parameters were evaluated non-invasively by generating LV pressure–volume loops (PVLs) through simultaneous echocardiography and blood pressure measurement. Results: A total of 24 children and teenagers (14.90 ± 2.27 years, 13 male) were included in the present study. Conventional echocardiographic parameters of LV function did not show significant differences between both beverage groups. The non-invasive generation of LV PVLs revealed a significantly lower cardiac efficiency 240 min after the ED consumption compared to the placebo intake (140.72 (133.21–149.73) mmHg vs. 135.60 (124.78–140.33) mmHg, p < 0.01). Conclusions: Acute ED consumption is associated with a significantly lower cardiac efficiency in healthy minors. The generation of non-invasive LV PVLs might be beneficial in the assessment of subtle changes in LV efficiency. Further studies need to investigate the influence of chronic ED consumption on LV function and morphology.

Myocardial infarction with non-obstructive coronary arteries (MINOCA) is common and occurs in 6–8% of all patients fulfilling the diagnostic criteria for acute myocardial infarction (AMI). This paper describes the rationale behind the trial ‘Randomized Evaluation of Beta Blocker and ACE-Inhibitor/Angiotensin Receptor Blocker Treatment (ACEI/ARB) of MINOCA patients’ (MINOCA-BAT) and the need to improve the secondary preventive treatment of MINOCA patients. MINOCA-BAT is a registry-based, randomized, parallel, open-label, multicenter trial with 2:2 factorial design. The primary aim is to determine whether oral beta blockade compared with no oral beta blockade, and ACEI/ARB compared with no ACEI/ARB, reduce the composite endpoint of death of any cause, readmission because of AMI, ischemic stroke or heart failure in patients discharged after MINOCA without clinical signs of heart failure and with left ventricular ejection fraction ≥40%. A total of 3500 patients will be randomized into four groups; e.g. ACEI/ARB and beta blocker, beta blocker only, ACEI/ARB only and neither ACEI/ARB nor beta blocker, and followed for a mean of 4 years. While patients with MINOCA have an increased risk of serious cardiovascular events and death, whether conventional secondary preventive therapies are beneficial has not been assessed in randomized trials. There is a limited basis for guideline recommendations in MINOCA. Furthermore, studies of routine clinical practice suggest that use of secondary prevention therapies in MINOCA varies considerably. Thus results from this trial may influence future treatment strategies and guidelines specific to MINOCA patients.

Older patients with acute decompensated heart failure (ADHF) have persistently poor outcomes including frequent rehospitalization despite guidelines-based therapy. We hypothesized that such patients have multiple, severe impairments in physical function, cognition, and mood that are not addressed by current care pathways. We prospectively examined frailty, physical function, cognition, mood, and quality of life in 27 consecutive older patients with ADHF at 3 medical centers and compared these with 197 participants in 3 age-matched cohorts: stable heart failure (HF) with preserved ejection fraction (n = 80), stable HF with reduced ejection fraction (n = 56), and healthy older adults (n = 61). Based on Fried criteria, frailty was present in 56% of patients with ADHF versus 0 for the age-matched chronic HF and health cohorts. Patients with ADHF had markedly reduced Short Physical Performance Battery score (5.3 ± 2.8) and 6-minute walk distance (178 ± 102 m) (p <0.001 vs other cohorts), with severe deficits in all domains of physical function: balance, mobility, strength, and endurance. In the patients with ADHF, cognitive impairment (78%) and depression (30%) were common, and quality of life was poor. In conclusion, older patients with ADHF are frequently frail with severe and widespread impairments in physical function, cognition, mood, and quality of life that may contribute to their persistently poor outcomes, are frequently unrecognized, are not addressed in current ADHF care paradigms, and are potentially modifiable with targeted interventions.