Heart failure with preserved ejection fraction (HFpEF) is a complex pathology that has undergone a paradigm shift in the last few years. As technology develops and diagnosis algorithms become more refined, early diagnosis leads to prompt medical management. This management has also changed in recent years. Moreover, HFpEF phenotyping attempts further nuance the management of patients with this disease. Whereas guidelines are not so firm on the medical classes of drugs that should be employed in HFpEF compared to HFrEF, new trials are on the way to change this. This literature review focuses on the evolution of diagnosis criteria for HFpEF, the clinical scores proposed by current guidelines, and also on the medical management of this pathology, focusing on medical management and how it has changed recently, by highlighting landmark trials that have been published on the topic or that are going to be published on the topic.
Two major trials, EMPA-REG OUTCOME trial (with Empagliflozin) and CANVAS trial (with Canagliflozin) have demonstrated the beneficial effects of SGLT2 inhibitors in patients with type 2 diabetes at risk for heart failure. SGLT2 inhibitors possess a unique pharmacological profile and have shown a significant reduction of hospitalization for heart failure in diabetic patients, immediately after treatment commencement. It seems that their effects are beneficial both in heart failure with reduced ejection fraction and heart failure with preserved ejection fraction. SGLT2 inhibitors reduce cardiovascular endpoints in patients with diabetes and high cardiovascular risk, most likely through a reduction of heart failure-related events. Empagliflozin treatment exerts beneficial effects on vascular function and central haemodynamics. Various mechanisms seem to contribute to the beneficial effects of SGLT2 inhibitors in heart failure. Taking into consideration their cardiovascular benefits and the number of ongoing trials with these drugs, there is a possibility to expand their indication to nondiabetic patients with heart failure. This review focuses on the newest insights into the beneficial effects of SGLT2 inhibitors on the cardiovascular system.
Cardiovascular-kidney-metabolic (CKM) syndrome describes the complex, bidirectional interplay among cardiovascular, renal, and metabolic dysfunctions, where impairment in one system accelerates decline in the others. This interconnected pathophysiology significantly elevates the risk and progression of heart disease, particularly heart failure, through mechanisms involving insulin resistance, systemic inflammation, neurohormonal activation, and endothelial dysfunction. In this context, therapeutic strategies targeting heart disease must address the multifaceted drivers of CKM. Recent advances highlight the need for an integrated, patient-centered approach that combines lifestyle interventions with pharmacological treatments tailored to individual cardiovascular risk. While foundational therapies such as RAAS inhibitors and statins remain essential, novel agents now offer additional prognostic and quality-of-life benefits. SGLT2 inhibitors have emerged as a cornerstone therapy, improving outcomes in heart failure with both preserved and reduced ejection fraction, independent of glycemic control. GLP-1 receptor agonists and dual GLP-1/GIP agonists like tirzepatide demonstrate cardiometabolic and renal protection, while finerenone shows promise in diabetic kidney disease and several heart failure phenotypes. These therapies not only target glycemic control but also reduce cardiovascular mortality, hospitalizations, and renal decline. Optimizing cardiovascular outcomes in CKM syndrome requires early, multifactorial therapeutic intervention, informed by evolving evidence and a deeper understanding of the heart–kidney–metabolism axis.
Chemotherapy is an important treatment in oncological disease, with a vast number of side effects. The cardiotoxicity of several chemotherapeutic agents and appropriate risk stratification and patient follow-up must be ensured by a multidisciplinary team which must include an oncologist and a cardiologist. Lynch syndrome is associated with younger-onset malignant tumors of various localizations, requiring aggressive chemotherapy. FOLFOX chemotherapy which is frequently used in Lynch syndrome-associated colorectal cancer has several cardiotoxic effects with mechanisms ranging from increased reactive oxidative species to Krebs cycle blockade or coronary vasospasm. These complex effects on the cardiovascular system have varied clinical effects, such as heart failure, arrhythmias, or acute ischemic events.
