Alessandra Greco

The right ventricle (RV) is a load-dependent chamber whose performance reflects myocardial reserve, loading conditions and ventricular interdependence. Volume overload, pressure overload and intrinsic myocardial dysfunction produce distinct, often overlapping remodelling trajectories and therapeutic targets. This review integrates contemporary imaging and prognostic evidence into a mechanism-to-decision framework. Its clinical contribution is to explain how deformation and chamber geometry should be interpreted with regurgitant burden and forward flow in volume overload, vascular load and coupling in pressure overload, and regional motion and tissue injury in intrinsic disease. Echocardiography combines these measurements with valve assessment, pulmonary outflow Doppler, left-heart filling phenotype and systemic venous congestion. Cardiovascular magnetic resonance, computed tomography, right heart catheterisation and stress testing resolve selected anatomical or physiological uncertainty. Automated measurements can support serial phenotyping but require image and contour review. Reverse remodelling describes favourable structural change; meaningful recovery additionally requires preserved or restored effective forward performance and improvement in clinical or venous consequences after treatment of the causal load, lesion or myocardial substrate. This framework helps recognise discordant findings, select further assessment and judge treatment response without equating a single load-dependent index with myocardial recovery.

Aims: The right ventricle (RV) is a major determinant of outcome in pulmonary arterial hypertension (PAH), but its assessment has not been completely incorporated in the risk of mortality scores. We therefore evaluated the added value of echocardiography of the RV to risk scores in a large multicentre European prospective cohort of patients with prevalent PAH enrolled in the ULTRAsound RIGHt venTricular eVALUation in PAH (ULTRA RIGHT VALUE) study. Methods and results: A total of 401 patients with prevalent PAH enrolled between January 2022 and December 2023 underwent an echocardiography and a risk assessment by Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) 2.0 and European Society of Cardiology (ESC)/European Respiratory Society (ERS) scoring systems. For both the ESC/ERS and REVEAL scores a one-unit decrease in any morphological parameter increased up to 69% and 92%, respectively, the odds for achieving/maintaining a low-risk status. Similarly, a one-unit increase in any RV functional parameter increased up to 1.28 and 1.78, respectively, the odds for achieving/maintaining a low-risk status. For this purpose, echocardiographic assessments of RV-PA coupling were the most performant. The inclusion of echocardiographic variables into the ESC/ERS and REVEAL 2.0 scores improved the c-index for morbi-mortality prediction from 0.73 [95% confidence interval (CI) 0.69–0.76] to 0.78 (95% CI 0.75–0.81; P < 0.01) and from 0.74 (95% CI 0.67–0.83) to 0.79 (95% CI 0.76–0.82; P < 0.01), respectively, with machine learning techniques showing indexes of RV-PA coupling having the highest influence on the c-index. Conclusion: Incorporation of echocardiographic parameters improves risk scores in PAH.

Background: Fluoropyrimidines are among the most common chemotherapeutic agents associated with cardiotoxicity, typically presenting as angina due to coronary vasospasm. Severe manifestations such as myocarditis and cardiogenic shock are rare, and rechallenge after cardiotoxicity is generally discouraged. We report a case of acute 5-fluorouracil–induced myocarditis with successful rechallenge after multidisciplinary evaluation. Case summary: A 30-year-old man with unresectable rectal adenocarcinoma developed acute cardiotoxicity during the first FOLFOX-6 cycle, presenting with abdominal pain and palpitations. ECG showed atrial fibrillation and ST-segment elevation. Echocardiography revealed severe biventricular dysfunction with elevated cardiac biomarkers. Coronary angiography excluded obstructive disease, and cardiac magnetic resonance confirmed acute myocarditis with diffuse oedema and non-ischaemic late gadolinium enhancement. Guideline-directed heart failure therapy led to rapid functional recovery within days. Following multidisciplinary cardio-oncology assessment, chemotherapy rechallenge under continuous monitoring was performed without recurrence of major adverse events. Subsequent cycles were well tolerated, and follow-up CMR showed preserved ventricular function with residual non-ischaemic LGE. Discussion: This case highlights the importance of early recognition of fluoropyrimidine cardiotoxicity, the role of multidisciplinary cardio-oncology management, and the potential feasibility of rechallenge in carefully selected patients.

BACKGROUND: Right ventricular functional adaptation to afterload is a major determinant of outcome in pulmonary arterial hypertension (PAH). We aimed to investigate if right ventricular-pulmonary artery (PA) coupling evaluated by the ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic pulmonary artery pressure (sPAP) improves risk assessment scores for survival prediction. METHODS: A total of 677 consecutive patients with PAH (55% idiopathic) were prospectively enrolled with follow-up clinical, right heart catheterization, and echocardiographic evaluations within 12 months (interquartile range, 180–344 days) after initiation of targeted therapies in 11 Italian centers. European Society of Cardiology/European Respiratory Society guidelines-derived risk scores and REVEAL 2.0 (US Registry to Evaluate Early and Long-Term PAH Disease Management 2.0) risk scores were collected at baseline and follow-up. 254 consecutive patients with PAH retrospectively enrolled in a German reference center served as a validation cohort. RESULTS: A low-risk status at a median of 3.7 years (interquartile range, 1.2–6.8) follow-up was significantly associated with each unit (0.1 mm/mm Hg) increase in TAPSE/sPAP under targeted therapies (European Society of Cardiology/European Respiratory Society score: odds ratio, 1.78; P ≤0.001; REVEAL 2.0 score: odds ratio, 1.43; P ≤0.001). At follow-up, the TAPSE/sPAP ratio increased the prognostic information of each risk stratum of the European Society of Cardiology/European Respiratory Society risk score, except the highest risk stratum, with 0.5 mm/mm Hg, 0.35 mm/mm Hg, and 0.30 mm/mm Hg, from the lowest to the intermediate-high risk score, identified as the best cutoff value. TAPSE/sPAP ratio increased the prognostic information of the REVEAL 2.0 score at follow-up, with 0.35 mm/mm Hg identified as the best cutoff value to discriminate within a score of 5 to 8, with no added value for scores 8. These results were confirmed in the validation cohort. CONCLUSIONS: Assessment of right ventricular-PA coupling by the TAPSE/sPAP ratio in PAH improves risk assessment scores except in the lowest or most advanced stage of the disease

Immunotherapy improved survival in a significant number of cancer patients as never before. Its benefits spread across cancer types and stages, and new drugs, new combination, and new indications are on the way. Both atherosclerosis and cancer are associated with the same risk factors, molecular processes, and a persistent inflammatory state that is attributed to immune system dysregulation. Clinicians are now facing a new category of patients that are long survivors/cured by immunotherapy. While short-to-medium-term side effects of immunotherapy are well characterized, long-term exposure to immune checkpoint inhibitors could be associated with new and unpredicted toxicity with a potential impact on survival, reducing the clear advantage of immunotherapy. Because of this, it is clear that the worsening of atherosclerosis emerges as the most relevant long-term side effect, translating into an increased incidence of atherosclerosis-related cardiovascular events, such as myocardial infarction, ischemic stroke, and peripheral artery disease. We review the available evidence of this relevant association, providing an overview for all clinicians involved in the multidisciplinary cancer care process.

Patients with active cancer and cancer survivors are at a markedly increased risk for developing cardiovascular comorbidities, including heart failure, coronary artery disease, and renal dysfunction, which are often compounded by the cardiotoxic effects of cancer therapies. This heightened cardiovascular vulnerability underscores the urgent need for effective, safe, and evidence-based cardioprotective strategies to reduce both cardiovascular morbidity and mortality. Sodium-glucose cotransporter 2 inhibitors (SGLT2is), a class of drugs originally developed for the treatment of type 2 diabetes, have demonstrated significant cardiovascular and renal benefits in high-risk populations, independent of glycemic control. Among the currently available SGLT2i, such as empagliflozin, canagliflozin, dapagliflozin, and sotagliflozin, there is growing evidence supporting their role in reducing major adverse cardiovascular events (MACEs), hospitalization for heart failure, and the progression of chronic kidney disease. Recent preclinical and clinical data suggest that SGLT2is exert cardioprotective effects through multiple mechanisms, including the modulation of inflammasome activity, specifically by reducing NLRP3 inflammasome activation and MyD88-dependent signaling, which are critical drivers of cardiac inflammation and fibrosis. Moreover, SGLT2is have been shown to enhance mitochondrial viability in cardiac cells, promoting improved cellular energy metabolism and function, thus mitigating cardiotoxicity. This narrative review critically evaluates the emerging evidence on the cardiorenal protective mechanisms of SGLT2is, with a particular focus on their potential role in cardio-oncology. We explore the common pathophysiological pathways between cardiovascular dysfunction and cancer, the molecular rationale for the use of SGLT2is in cancer patients, and the potential benefits in both primary and secondary prevention of cardiovascular toxicity related to oncological treatments. The aim is to propose a therapeutic paradigm utilizing SGLT2is to reduce cardiovascular mortality, MACE, and the burden of cardiotoxicity in high-risk oncology patients, fostering an integrated approach to cardio-oncology care.

Aim: Significant tricuspid regurgitation (TR) may be a confounding factor when assessing right ventricular (RV) function with imaging techniques. Global myocardial work (GMW) has been proposed as a non-invasive surrogate of RV pressure–volume loops, and it might provide a more accurate evaluation of RV performance than standard echocardiographic parameters, accounting for both afterload and myocardial work efficiency. The aim of this study was to assess the relationship between RV GMW and hemodynamic indices of prognostic significance in pulmonary hypertension (PH) and to compare RV GMW in PH patients with or without TR. Methods: This was a proof-of-concept study. Thirty consecutive patients with PH undergoing diagnostic right heart catheterization (RHC) in sinus rhythm were enrolled. Echocardiography was performed in all patients within two hours of RHC. Results: Global work efficiency (GWE) was directly correlated (r = 0.562, p = 0.006), whereas global wasted work (GWW) was inversely correlated with stroke volume index (r = –0.447, p = 0.037). Poorer correlation was observed with tricuspid annular plane systolic excursion (TAPSE), and no correlation was observed with TAPSE/sPAP (ratio of TAPSE to systolic pulmonary artery pressure). Patients with moderate/severe TR had lower GWE [83% (77–89%) vs. 96% (94–96%), p < 0.001] and higher GWW [137% (90–179%) vs. 25% (18–89%), p = 0.002]. Similar results were obtained when the analysis was applied to subgroups of patients stratified according to either preserved or poor TAPSE/sPAP. Conclusions: RV myocardial work is more strongly associated with hemodynamic indicators of prognosis in PH than standard echocardiographic parameters. Patients with moderate/severe TR have significantly lower values of work efficiency and higher values of wasted work as compared to those without significant TR.

Cancer patients, especially long cancer survivors, are exposed to several cardio-metabolic diseases, including diabetes, heart failure, and atherosclerosis, which increase their risk of cardiovascular mortality. Therapy with glucagon-like peptide 1 (GLP1) receptor agonists demonstrated several beneficial cardiovascular effects, including atherosclerosis and heart failure prevention. Cardiovascular outcome trials (CVOTs) suggest that GLP-1 RA could exert cardiorenal benefits and systemic anti-inflammatory effects in patients with type-2 diabetes through the activation of cAMP and PI3K/AkT pathways and the inhibition of NLRP-3 and MyD88. In this narrative review, we highlight the biochemical properties of GLP-1 RA through a deep analysis of the clinical and preclinical evidence of the primary prevention of cardiomyopathies. The overall picture of this review encourages the study of GLP-1 RA in cancer patients with type-2 diabetes, as a potential primary prevention strategy against heart failure and atherosclerosis.

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Background: The incidence of breast cancer is rising worldwide. Recent advances in systemic and local treatments have significantly improved survival rates of patients having early breast cancer. In the last decade, great attention has been paid to the prevention and early detection of cardiotoxicity induced by breast cancer treatments. Systemic therapy-related cardiac toxicities have been extensively studied. Radiotherapy, an essential component of breast cancer treatment, can also increase the risk of heart diseases. Consequently, it is important to balance the expected benefits of cancer treatment with cardiovascular risk and to identify strategies to prevent cardiotoxicity and improve long-term outcomes and quality of life for these patients. Objective: This CardioTox Breast study aims to investigate the use of cardiac imaging, based on cardiac magnetic resonance and echocardiography, and to identify associated circulating biomarkers to assess early tissue changes in chemo-induced and radiation-induced cardiotoxicity in the time window of 12 months after the end of radiotherapy in patients with breast cancer. Methods: The CardioTox Breast trial is a multicenter observational prospective longitudinal study. We aim to enroll 150 women with stage I-III unilateral breast cancer, treated with breast conserving surgery, who planned to receive radiotherapy with or without systemic therapy. Baseline and follow-up data include cardiac measurements based on cardiac magnetic resonance imaging, echocardiography, and circulating biomarkers of cardiac toxicity. Results: This study details the protocol of the CardioTox Breast trial. Recruitment started in September 2020. The results of this study will not be published until data are mature for the final analysis of the primary study end point. Conclusions: The CardioTox Breast study is designed to investigate the effects of systemic and radiation therapy on myocardial function and structure, thus providing additional evidence on whether cardiac magnetic resonance is the optimal screening imaging for cardiotoxicity.