After progressively receding for decades, cardiovascular mortality due to coronary artery disease has recently increased, and the associated healthcare costs are projected to double by 2030. While the 2019 European Society of Cardiology guidelines for chronic coronary syndromes recommend non-invasive cardiac imaging for patients with suspected coronary artery disease, the impact of non-invasive imaging strategies to guide initial coronary revascularization and improve long-term outcomes is still under debate. Recently, the ISCHEMIA trial has highlighted the fundamental role of optimized medical therapy and the lack of overall benefit of early invasive strategies at a median follow-up of 3.2 years. However, sub-group analyses excluding procedural infarctions with longer follow-ups of up to 5 years have suggested that patients undergoing revascularization had better outcomes than those receiving medical therapy alone. A recent sub-study of ISCHEMIA in patients with heart failure or reduced left ventricular ejection fraction (LVEF <45%) indicated that revascularization improved clinical outcomes compared to medical therapy alone. Furthermore, other large observational studies have suggested a favorable prognostic impact of coronary revascularization in patients with severe inducible ischemia assessed by stress cardiovascular magnetic resonance (CMR). Indeed, some data suggest that stress CMR-guided revascularization assessing the extent of the ischemia could be useful in identifying patients who would most benefit from invasive procedures such as myocardial revascularization. Interestingly, the MR-INFORM trial has recently shown that a first-line stress CMR-based non-invasive assessment was non-inferior in terms of outcomes, with a lower incidence of coronary revascularization compared to an initial invasive approach guided by fractional flow reserve in patients with stable angina. In the present review, we will discuss the current state-of-the-art data on the prognostic value of stress CMR assessment of myocardial ischemia in light of the ISCHEMIA trial results, highlighting meaningful sub-analyses, and still unanswered opportunities of this pivotal study. We will also review the available evidence for the potential clinical application of quantifying the extent of ischemia to stratify cardiovascular risk and to best guide invasive and non-invasive treatment strategies.

Background: Studies have shown significant benefits of exercise therapy in heart failure (HF) with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF). The mechanisms responsible for the beneficial effect of exercise in HFrEF and HFpEF are still unclear. We hypothesized that the effect of exercise on myocardial remodeling may explain its beneficial effect. Methods: IMAGING-REHAB-HF is a single-center, randomized, controlled clinical trial using cardiac magnetic resonance imaging, vasomotor endothelial function, cardiac sympathetic activity imaging and serum biomarkers to compare the effect of exercise therapy in HFpEF (LVEF ≥ 45%) and HFrEF (LVEF < 45%). Subjects will be assessed at baseline and after 4 months. The exercise program will consist of three 60-min exercise sessions/week. The primary endpoints are the effect of exercise on myocardial extracellular volume (ECV), left ventricular (LV) systolic function, LV mass, LV mass-to-volume and LV cardiomyocyte volume. Secondary endpoints include the effect of exercise on vasomotor endothelial function, cardiac sympathetic activity and plasmatic biomarkers. Patients will be allocated in a 2:1 fashion to supervised exercise program or usual care. A total sample size of 90 patients, divided into two groups according to LVEF:HFpEF group (45 patients:30 in the intervention arm and 15 in the control arm) and HFrEF group (45 patients:30 in the intervention arm and 15 in the control arm) – will be necessary to achieve adequate power. Conclusion: This will be the first study to evaluate the benefits of a rehabilitation program on cardiac remodeling in HF patients. The unique design of our study may provide unique data to further elucidate the mechanisms involved in reverse cardiac remodeling after exercise in HFpEF and HFrEF patients.

Aims Despite of recent advances in the pharmacological treatment, heart failure (HF) maintains significant morbidity and mortality rates. While serum potassium disorders are common and associated with adverse outcomes, the exact recommended potassium level for patients with HF are not entirely established. We aimed to investigate the prognostic role of potassium levels on a cohort of patients with symptomatic chronic HF. Methods and results Patients with symptomatic chronic HF were identified at the referral to 6 min walking test (6MWT) and were prospectively followed up for cardiovascular events. Clinical and laboratorial data were retrospectively obtained. The primary endpoint was the composite of cardiovascular death, hospitalization due to HF, and heart transplantation. The cohort included 178 patients with HF with the mean age of 51 ± 12.76 years, 39% were female, 85% of non-ischaemic cardiomyopathy, and 38% had New York Heart Association Class III with a relatively high Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) score (12.91 ± 6.6). The mean left ventricular ejection fraction was 39.98 ± 15.79%, and the mean 6MWT distance was 353 ± 136 m. After a median follow-up of 516 days, there were 22 major cardiovascular events (4 cardiovascular deaths, 13 HF admissions, and 5 heart transplants). Patients were stratified according to cut-point level of serum potassium of 4.7 mmol/L to predict combined cardiac events based on receiver operating characteristic analysis. Individuals with higher potassium levels had worse renal function (glomerular filtration rate, K ≤ 4.7: 102.8 ± 32.2 mL/min/1.73 m 2 vs. K > 4.7: 85.42 ± 36.2 mL/min/1.73 m 2 , P = 0.004), higher proportion of New York Heart Association Class III patients (K ≤ 4.7: 28% vs.

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Introduction: Physiological and pathological cardiac hypertrophy differ in terms of mechanisms, phenotypes, and outcomes. We aimed to characterize the cardiac tissue phenotype of athletes and HF patients. Methods: Prospectively enrolled participants underwent CMR and CPET. HF patients (NYHA class II-III) were classified as HFpEF (LVEF>=45%) or HFrEF (LVEF<45%). Results: One-hundred and eighty participants were categorized in four groups: athletes (n=44, 32±12 years), HFpEF (n=47, 61±11 years, H2FPEF score 5±2), HFrEF (n=47, 54±10 years), and healthy controls (n=42, 41±13 years). LVEF was markedly reduced in HFrEF (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p<.001). LV mass index (athletes 65±6%, HFpEF 59±11, HFrEF 29±9, controls 66±4, p<.001) and cardiomyocyte mass index (athletes 64±15g/m 2 , HFpEF 66±24, HFrEF 82±36, controls 42±8, p<.001) were greater in athletes and in HF patients (Fig 1A). Athletes and HFpEF patients had concentric LV remodeling, while HFrEF patients showed eccentric remodeling (Fig 1B). Intracellular lifetime of water was longer in athletes and shorter in HFrEF (athletes .17±.07s, HFpEF .15±.05, HFrEF .13±.05, controls .14±.05, p<.001) (Fig 2A). ECV was similarly increased in both HF groups (athletes .28±.04%, HFpEF .31±.05, HFrEF .31±.05, controls .28±.04, p<.001) (Fig 2B). Native T1 (athletes 1175±55ms, HFpEF 1261±61, HFrEF 1274±61, controls 1229±75, p=.01) correlated with CPET maximal oxygen consumption (VO 2 max) in HF patients (r=-.023, p=.048) (athletes 52±10, HFpEF 18±6, HFrEF 17±4, controls 29±9, p<.001). Conclusion: Physiological hypertrophy was characterized by increased cardiomyocyte diameter, normal ECV, and shorter native T1 due to its greater cardiomyocyte volume. Contrastingly, pathological hypertrophy’s longer native T1 was a result of its higher ECV and correlated with VO 2 max in HF. Cardiomyocyte diameter was smaller in HFrEF than in HFpEF.