Maria João Ferreira

Heart failure with preserved ejection fraction (HFpEF) remains a major health concern with limited therapeutic options. Growing evidence supports the multiple benefits of ketones in heart disease, but their impact on HFpEF remains unknown. We investigated whether increasing ketones can help to manage HFpEF. Using the ZSF1 rat model of HFpEF, 16‐week‐old rats were randomly assigned to one of three subgroups: (i) control diet; (ii) ketogenic diet (KD); or (iii) control diet with added exogenous ketone salts (KS) in their drinking water for 10 weeks. We found that both KD and KS ameliorated the HFpEF phenotype by improving structural echocardiographic parameters, lowering glycaemia and lipid profiles, and reducing HFpEF‐related fibrosis and hypertrophy without impacting in vivo diastolic function. Nevertheless, ex vivo cardiomyocyte preparations showed improved calcium handling and myofilament relaxation, suggesting benefits at the cellular level. Interestingly, KD still proved effective, despite the potentially adverse increase in fat mass. There was decreased myofilament Ca²⁺ sensitivity and normalized active and passive tension in both groups, especially KS. These results suggest that providing ketone through the diet or supplements could be a valuable strategy to complement HFpEF treatment. Given the well‐known challenges of implementing dietary changes, exogenous KS offer a more practical and effective option to achieve these benefits. image Key points: Ketogenic diet and ketone salts effectively reversed the cardiac structural impairments associated with the ZSF1 Obese heart failure with preserved ejection fraction (HFpEF) phenotype by ameliorating left ventricular mass. Both treatments reduced fibrosis and hypertrophy, leading to improved or, in the case of ketone salts, even reversed cardiomyocyte contractile and relaxation performance. Ketone salts also reversed HFpEF‐related cardiomyocyte stiffness and prevented a reduction in the development of maximum force. Both treatments improved myofilament Ca²⁺ sensitivity. Both treatments also improved the metabolic profile, reducing hyperglycaemia, blood triglycerides and levels of NT‐proBNP, a well‐known biomarker of worsening heart failure.

Hypertrophic cardiomyopathy (HCM) is a heterogeneous cardiac disease and one of its major challenges is the limited accuracy in stratifying the risk of sudden cardiac death (SCD). Positron emission tomography (PET), through the evaluation of myocardial blood flow (MBF) and metabolism using fluorodeoxyglucose (FDG) uptake, can reveal microvascular dysfunction, ischemia, and increased metabolic demands in the hypertrophied myocardium. These abnormalities are linked to several factors influencing disease progression, including arrhythmia development, ventricular dilation, and myocardial fibrosis. Fibroblast activation can also be evaluated using PET imaging, providing further insights into early-stage myocardial fibrosis. Conflicting findings underscore the need for further research into PET’s role in risk stratification for HCM. If PET can establish a connection between parameters such as abnormal MBF or increased FDG uptake and SCD risk, it could enhance predictive accuracy. Additionally, PET holds significant potential for monitoring therapeutic outcomes. The aim of this review is to provide a comprehensive overview of the most significant data on disease progression, risk stratification, and prognosis in patients with HCM using cardiac PET-CT imaging.

Introduction: High-sensitivity troponin (hsTn) has a very high diagnostic accuracy for myocardial infarction (MI), and patients who were formerly diagnosed with unstable angina (UA) are being reclassified as having NSTEMI in the era of hsTn. This paradigm shift has changed the clinical features of UA, which remain poorly characterized, specifically the occurrence of obstructive coronary artery disease (CAD) and the need for myocardial revascularization. The main purpose of this study was to clinically characterize contemporary UA patients, assess predictors of obstructive CAD, and develop a risk model to predict significant CAD in this population. Methods: We conducted a retrospective cohort study of 742 patients admitted to the hospital with UA. All patients underwent coronary angiography. The endpoint of the study was the presence of obstructive CAD on angiography. The cohort was divided into two groups: patients with significant coronary artery disease (CAD+) and those without CAD (CAD–). We developed a score (UA CAD Risk) based on the multivariate model and compared it with the GRACE, ESC, and TIMI risk scores using ROC analysis. Results: Obstructive CAD was observed on angiography in 53% of the patients. Age, dyslipidemia, troponin level, male sex, ST-segment depression, and wall motion abnormalities on echocardiography were independent predictors of obstructive CAD. hsTn levels (undetectable vs. nonsignificant detection) had a negative predictive value of 81% to exclude obstructive CAD. We developed a prediction model with obstructive CAD as the outcome (AUC: 0.60). Conclusions: In a contemporary UA cohort, approximately 50% of the patients did not have obstructive CAD on angiography. Commonly available cardiac tests at hospital admission show limited discrimination power in identifying patients at risk of obstructive CAD. A revised diagnostic and etiology algorithm for patients with UA is warranted.

Background Chronic coronary total occlusion (CTO) is a common finding in patients referred to coronary angiography. To sustain blood flow distally to the occlusion site, collateral circulation is formed from preexisting vessels. While these collaterals may partial or completely preserve perfusion at rest, they may be insufficient when increased blood flow is needed. According to current guidelines, percutaneous coronary intervention (PCI) is recommended solely in patients with resistant angina despite optimal medical therapy or when a large area of documented ischemia in the territory of the occluded vessel is present. Randomised controlled trials (RCTs) suggest its benefit in the improvement of patients’ quality of life and symptoms, despite their conflicting results concerning prognosis and left ventricular function. However, most of these studies often lack data regarding myocardial ischemic burden and viability, assessed by imaging methods. Therefore, the purpose of the systematic review is to comprise and analyse the literature on whether viability or ischemia-guided PCI of CTO, identified by imaging methods, has an impact on the clinical outcomes of the patients. Methods We will conduct a thorough research in different databases, including PubMed/MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science Core Collection, Clinical trials in the European Union, and ClinicalTrials.gov. We will include RCTs, cohort studies, cross-sectional studies, and case-control studies, in which patients with established CTO were tested for viability and/or ischemia before the decision to perform PCI and were evaluated by post-intervention testing or clinical endpoint follow-up. Two authors will independently review the selected studies, and any discrepancies will be solved by a third element. Subsequently, data from the various eligible studies will be extracted and analysed by two different authors. No subgroup analysis is planned. Ethics and disclosure Ethical approval will not be required for this study as it is an analysis of previously published articles (i.e., secondary data). The results will be published in a peer-reviewed journal. PROSPERO registration CRD42023426858.

With advances in scanner technology, postprocessing techniques, and the development of novel positron emission tomography (PET) tracers, the applications of PET for the study of coronary heart disease have been gaining momentum in the last few years. Depending on the tracer and acquisition protocol, cardiac PET can be used to evaluate the atherosclerotic lesion (plaque imaging) and to assess its potential consequences—ischemic versus nonischemic (perfusion imaging) and viable versus scarred (viability imaging) myocardium. The scope of this review is to summarize the role of PET in coronary heart disease.