Exercise intolerance, indicated by dyspnea and fatigue during exertion, is a cardinal manifestation of heart failure (HF). Cardiopulmonary exercise testing (CPET) precisely defines maximum exercise capacity through measurement of peak oxygen uptake (VO2). Peak VO2 values have a critical role in informing patient selection for advanced HF interventions such as heart transplantation and ventricular assist devices. Oxygen uptake and ventilatory patterns obtained during the submaximal portion of CPET are also valuable to recognize because of their ease of ascertainment during low-level exercise, relevance to ability to perform activities of daily living, independence from volitional effort, and strong relationship to prognosis in HF. The ability of peak VO2 and other CPET variables to be measured reproducibly and to accurately reflect HF severity is increasingly recognized and endorsed by scientific statements. Integration of CPET with invasive hemodynamic monitoring and cardiac imaging during exercise provides comprehensive characterization of multisystem reserve capacity that can inform prognosis and the need for cardiac interventions. Here, we review both practical aspects of conducting CPETs in patients with HF for clinical and research purposes as well as interpretation of gas exchange patterns across the spectrum of preclinical HF to advanced HF.

Purpose We evaluated whether the severe acute respiratory syndrome coronavirus 2 pandemic was associated with changes in the pattern of acute cardiovascular admissions across European centres. Methods We set-up a multi-centre, multi-national, pan-European observational registry in 15 centres from 12 countries. All consecutive acute admissions to emergency departments and cardiology departments throughout a 1-month period during the COVID-19 outbreak were compared with an equivalent 1-month period in 2019. The acute admissions to cardiology departments were classified into 5 major categories: acute coronary syndrome, acute heart failure, arrhythmia, pulmonary embolism and other. Results Data from 54331 patients were collected and analysed. Nine centres provided data on acute admissions to emergency departments comprising 50384 patients: 20226 in 2020 vs 30158 in 2019 – incidence rate ratio (IRR) with 95% confidence interval (95%CI): 0.66(0.58-0.76). The risk of death at the emergency departments was higher in 2020 vs 2019: odds ratio (OR) with 95%CI: 4.1(3.0-5.8), P<0.0001. All 15 centers provided data on acute cardiology departments admissions: 3007 patients in 2020 vs 4452 in 2019, respectively, IRR(95%CI): 0.68(0.64-0.71). In 2020, there were less admissions with IRR(95%CI): acute coronary syndrome: 0.68(0.63-0.73), acute heart failure: 0.65(0.58-0.74), arrhythmia: 0.66(0.60-0.72), other: 0.68(0.62-0.76); we found a relatively higher percentage of pulmonary embolism admissions in 2020: OR(95%CI): 1.5(1.1-2.1), P=0.02. Among patients with acute coronary syndrome there were fewer admissions with unstable angina: 0.79(0.66-0.94), non-ST segment elevation myocardial infarction: 0.56(0.50-0.64) and ST-segment elevation myocardial infarction: 0.78(0.68-0.89). Conclusion In the European centres during the COVID-19 outbreak, there were fewer acute cardiovascular admissions. Also, fewer patients were admitted to the emergency departments with 4-times higher death risk at the emergency departments.

The autonomic nervous system, the renin-angiotensin-aldosterone system, and the natriuretic peptide system represent critical regulatory pathways in heart failure and as such have been the major targets of pharmacological development. The introduction and approval of angiotensin receptor neprilysin inhibitors (ARNi) have broadened the available drug treatments of patients with chronic heart failure with reduced ejection fraction. Neprilysin catalyses the degradation of a number of vasodilator peptides, including the natriuretic peptides, bradykinin, substance P, and adrenomedullin, as well as vasoconstrictor peptides, including endothelin-1 and angiotensin I and II. We review the multiple, potentially competing, substrates for neprilysin inhibition, and the resultant composite clinical effects of ARNi therapy. A mechanistic understanding of this novel therapeutic class may provide important insights into the expected on-target and off-target effects when this agent is more widely prescribed.

Heart failure (HF) with preserved ejection fraction (HFpEF) is a heterogeneous clinical syndrome characterized by cardiovascular, metabolic, and pro‐inflammatory diseases associated with advanced age and extracardiac comorbidities. All of these conditions finally lead to impairment of myocardial structure and function. The large phenotypic heterogeneity of HFpEF from pathophysiological underpinnings presents a major hurdle to HFpEF therapy. The new therapeutic approach in HFpEF should be targeted to each HF phenotype, instead of the ‘one‐size‐fits‐all’ approach, which has not been successful in clinical trials. Unless the structural and biological determinants of the failing heart are deeply understood, it will be impossible to appropriately differentiate HFpEF patients, identify subtle myocardial abnormalities, and finally reverse abnormal cardiac function. Based on evidence from endomyocardial biopsies, some of the specific cardiac structural phenotypes to be targeted in HFpEF may be represented by myocyte hypertrophy, interstitial fibrosis, myocardial inflammation associated with oxidative stress, and coronary disease. Once the diagnosis of HFpEF has been established, a potential approach could be to use a panel of biomarkers to identify the main cardiac structural HFpEF phenotypes, guiding towards more appropriate therapeutic strategies. Accordingly, the purpose of this review is to investigate the potential role of biomarkers in identifying different cardiac structural HFpEF phenotypes and to discuss the merits of a biomarker‐guided strategy in HFpEF.