Background: The search for reliable cardiac functional parameters is crucial in patients with mitral regurgitation (MR). In the Italian arm of the European Registry of MR, we compared the ability of global longitudinal strain (GLS) and left ventricular (LV) ejection fraction (LVEF) to detect cardiac damage in MR. Methods: Five hundred four consecutive patients with MR underwent a complete echo-Doppler exam. A total of 431, 53 and 20 patients had degenerative, secondary and mixed MR, respectively. The main echocardiographic parameters, including LV and left atrial (LA) size measurements, pulmonary artery systolic pressure (PASP) and GLS were compared between patients with mild MR (n = 392) vs. moderate to severe MR (n = 112). Results: LVEF and GLS were related one another in the pooled population, and separately in patients with mild and moderate/severe MR (all p < 0.0001). However, a certain number of patients were above the upper or below the lower limits of the 95% confidence interval (CI) of the normal relation in the pooled population and in patients with mild MR. Only 2 patients were below the 95% CI in moderate to severe MR. After adjusting for confounders by separate multivariate models, LVEF and GLS were independently associated with LV and left atrial size in the pooled population and in mild and moderate/severe MR. GLS, but not LVEF, was also independently associated with PASP in patients with mild and moderate to severe MR. Conclusions: Both LVEF and GLS are independently associated with LV and LA size, but only GLS is related to pulmonary arterial pressure. GLS is a powerful hallmark of cardiac damage in MR.

Background: Left ventricular (LV) and right ventricular (RV) dysfunction is recognized in idiopathic pulmonary fibrosis (IPF). Little is known about cardiac involvement in non-idiopathic pulmonary fibrosis (no-IPF). This issue can be explored by advanced echocardiography. Methods: Thirty-three clinically stable and therapy-naive fibrotic IPF and 28 no-IPF patients, and 30 healthy controls were enrolled. Exclusion criteria were autoimmune systemic diseases, coronary disease, heart failure, primary cardiomyopathies, chronic obstructive lung diseases, pulmonary embolism, primary pulmonary hypertension. Lung damage was evaluated by diffusion capacity for carbon monoxide (DLCO_sb). All participants underwent an echo-Doppler exam including 2D global longitudinal strain (GLS) of both ventricles and 3D echocardiographic RV ejection fraction (RVEF). Results: We observed LV diastolic dysfunction in IPF and no-IPF, and LV GLS but not LV EF reduction only in IPF. RV diastolic and RV GLS abnormalities were observed in IPF versus both controls and no-IPF. RV EF did not differ significantly between IPF and no-IPF. DLCO_sb and RV GLS were associated in the pooled pulmonary fibrosis population and in the IPF subgroup (β = 0.708, p < 0.001), independently of confounders including pulmonary arterial systolic pressure. Conclusion: Our data highlight the unique diagnostic capabilities of GLS in distinguishing early cardiac damage of IPF from no-IPF patients.

Background: The coupling of the right ventricle (RV) to the pulmonary circulation is an indicator of RV performance that can be non-invasively estimated by echocardiography. There are no data about its use in patients affected by fibrotic interstitial lung diseases (f-ILD). Methods: Fifty f-ILD patients, including 27 cases with idiopathic pulmonary fibrosis (IPF) (M = 37; mean age 67 ± 7 years), were studied with standard and speckle-tracking echocardiography and compared with 30 age-matched healthy volunteers. The mean patient follow-up was 70 ± 4 months. Results: Fibrotic ILD patients had a larger right ventricle (RV) and worse diastolic function because the RV global longitudinal strain (GLS) was significantly lower and the systolic pulmonary artery pressure (sPAP) estimates were higher in comparison with those of controls. Conversely, tricuspid annular systolic excursion (TAPSE) did not differ between controls and patients. Median values of TAPSE/sPAP and RV GLS/sPAP were significantly reduced in f-ILD patients (p < 0.0001). Patients with an RV GLS/sPAP below the median value had a shorter survival time (61 vs. 74 months, p = 0.01); this parameter was an independent predictor of a worse outcome. Conclusion: Low estimates of RV GLS/sPAP are predictive of worse outcomes in f-ILD patients. RV coupling seems to be a promising surrogate biomarker of RV performance to discriminate the patient phenotype with significant management and prognosis implications.

Obesity is a multidimensional condition characterized by autonomic imbalance, metabolic inflexibility, impaired physical resilience, and ectopic adiposity, pathophysiological alterations that arise long before overt cardiometabolic disease becomes clinically detectable. Despite this, current cardiometabolic risk scores continue to rely predominantly on biochemical and anthropometric variables, such as BMI, waist circumference, glucose, and lipid levels. While these markers are practical, inexpensive, and validated across large population cohorts, growing evidence shows that they offer limited incremental predictive value and fail to capture early functional and structural abnormalities. The recent literature highlights the prognostic importance of autonomic dysfunction, reduced metabolic flexibility, diminished cardiorespiratory fitness, impaired muscular strength, and ectopic fat depots including visceral and epicardial adiposity, independently of the traditional anthropometric indices. The domains remain absent from traditional algorithms such as the Metabolic Syndrome criteria, the Framingham Risk Score, and SCORE2. As a result, cardiometabolic risk is frequently underestimated in key subgroups, including young adults with obesity, individuals with high visceral adiposity but normal BMI, those with subclinical myocardial dysfunction, and metabolically unhealthy normal-weight phenotypes. This narrative review synthesizes current evidence on obesity-related cardiometabolic impairment, highlights major gaps in established risk scores, and supports the conceptual development of the C.O.R.E. (Cardio-Obesity Risk Evaluation) Indicator Model—a hypothesis-generating, non-validated multidomain framework integrating autonomic, metabolic, functional, and structural markers to enable earlier risk phenotyping in future studies.

Cardiometabolic diseases remain the leading cause of morbidity and mortality worldwide, despite major advances in pharmacological and lifestyle interventions. Exercise training is a cornerstone of prevention and treatment; however, adherence to traditional aerobic programs remains suboptimal. Isometric handgrip (IHG) training has emerged as a simple, time-efficient, and potentially effective strategy for improving cardiovascular and metabolic outcomes. This state-of-the-art review synthesizes current evidence on the physiological mechanisms underlying IHG training, including autonomic modulation, vascular function improvement, endothelial adaptation, and metabolic regulation. We summarize clinical data regarding its effects on blood pressure, arterial stiffness, endothelial function, insulin sensitivity, and inflammatory markers. Special attention is given to its applicability in specific populations, including hypertensive patients, individuals with metabolic syndrome, heart failure patients, and cancer survivors. We also discuss methodological heterogeneity across studies, safety considerations, and knowledge gaps. Finally, we outline future research directions needed to define optimal protocols and clarify long-term cardiometabolic benefits. IHG training represents a promising adjunctive strategy within cardiometabolic prevention and rehabilitation programs.

The management of severe asthma has shifted from symptom control to the ambition of remission, a goal borrowed from rheumatology. Biologics targeting immunoglobulin E, interleukin-5 and its receptor, the interleukin-4 receptor alpha subunit, and thymic stromal lymphopoietin have made sustained quiescence realistic for many patients, yet estimates that roughly one-third achieve remission shift by tens of percentage points depending on the definition used. This narrative review advances two linked arguments. First, that the heterogeneity of definitions, not any shortage of effective agents, is the central obstacle to using remission as a treatment target. Second, that remission is best read as a multidimensional construct in which clinical, functional and biological quiescence are distinct axes, reached independently and often discordantly, with complete remission denoting their convergence rather than the last step of a sequence. Where each biologic acts within the type 2 cascade determines which biomarkers move under treatment and, only hypothetically, how deep remission can reach. Structural remodeling and the fact that current agents suppress rather than reset inflammation cap that depth, so remission remains a pharmacologically maintained state on treatment. Concomitant chronic rhinosinusitis with nasal polyps is treated as a modifier of asthma remission rather than a separate endpoint. The framework is conceptual and unvalidated. The priority is a harmonized, depth-resolved definition, explicit about treatment burden and patient-centered outcomes, against which any therapy can be judged.