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19 pages, 989 KB  
Systematic Review
Right Ventricular Strain and RV–Pulmonary Artery Coupling in Systemic Sclerosis: A Systematic Review
by Elena Cealera, Maria-Magdalena Gurzun, Alexandra-Cristiana Gache, Monica Steluta Marc, Irinel Raluca Parepa and Elena Dantes
J. Clin. Med. 2026, 15(9), 3368; https://doi.org/10.3390/jcm15093368 - 28 Apr 2026
Viewed by 42
Abstract
Background: Right ventricular (RV) dysfunction is a key contributor to morbidity and mortality in systemic sclerosis (SSc), emerging from the combined effects of microvascular disease, myocardial fibrosis, interstitial lung involvement, and increasing pulmonary vascular load. Conventional echocardiography frequently fails to detect early [...] Read more.
Background: Right ventricular (RV) dysfunction is a key contributor to morbidity and mortality in systemic sclerosis (SSc), emerging from the combined effects of microvascular disease, myocardial fibrosis, interstitial lung involvement, and increasing pulmonary vascular load. Conventional echocardiography frequently fails to detect early RV impairment, prompting growing interest in deformation-based parameters such as RV free-wall longitudinal strain (RV-FWS), global longitudinal strain (RV-GLS), and RV–pulmonary artery (PA) coupling indices. Although natriuretic peptides reflect myocardial stress and are widely used in cardiopulmonary diseases, their integration with advanced RV imaging has been inconsistently reported in SSc. This systematic review synthesizes available evidence on RV strain, RV–PA coupling, and their relationship with clinical outcomes and biomarkers in SSc. Methods: A systematic search was conducted to identify clinical studies evaluating RV strain (RV-FWS, RV-GLS), right atrial strain, or RV–PA coupling indices in adult patients with SSc or SSc-associated pulmonary arterial hypertension (SSc-PAH). Eligible studies included those using speckle-tracking echocardiography or cardiac magnetic resonance feature-tracking. Study selection and data extraction were performed in accordance with PRISMA guidelines. Results: Seven studies met the eligibility criteria. Across unselected SSc cohorts, early disease without pulmonary hypertension (PH), and right-heart-catheterization-confirmed SSc-PAH, RV strain consistently detected myocardial impairment even when conventional echocardiographic indices remained normal. RV-FWS and RV-GLS were commonly reduced, and longitudinal data demonstrated progressive deterioration independent of standard measures. Strain-derived RV–PA coupling, particularly RV-FWS/PASP, significantly improved prognostic stratification when added to established PAH risk models. Two studies identified impaired RV deformation as a predictor of mortality, and CMR-derived right atrial strain provided additional prognostic value. Biomarker integration was limited, with only one study reporting an association between natriuretic peptide elevation (NT-proBNP) and impaired RV–PA coupling suggesting that biomarkers may reflect the hemodynamic load, although evidence remains limited captured by strain abnormalities. Conclusions: RV strain and RV–PA coupling indices are more sensitive than conventional echocardiography for detecting early RV dysfunction, monitoring disease progression, and predicting adverse outcomes in SSc. Although biomarker evidence remains limited, available data suggest that natriuretic peptides may provide complementary information to deformation-based assessment, although current evidence remains limited by reflecting combined myocardial and pulmonary vascular load. Standardized prospective studies including both strain imaging and biomarkers are needed to clarify the integrated diagnostic and prognostic value of advanced RV assessment in SSc. Full article
(This article belongs to the Special Issue Advances in Pulmonary Disease Management and Innovation in Treatment)
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27 pages, 1434 KB  
Article
Prognostic Role of Immunonutritional Indices in Elderly Patients with HFpEF: Long-Term Follow-Up of the CONUT, PNI, and CALLy Scores
by Andrea Sonaglioni, Chiara Lonati, Andrea Donzelli, Federico Napoli, Gian Luigi Nicolosi, Massimo Baravelli, Michele Lombardo and Sergio Harari
J. Clin. Med. 2026, 15(9), 3245; https://doi.org/10.3390/jcm15093245 - 24 Apr 2026
Viewed by 109
Abstract
Background: Malnutrition and systemic inflammation are increasingly recognized as important determinants of prognosis in patients with heart failure. Several immunonutritional indices, including the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, and the C-reactive protein–albumin–lymphocyte (CALLy) index, have been proposed as [...] Read more.
Background: Malnutrition and systemic inflammation are increasingly recognized as important determinants of prognosis in patients with heart failure. Several immunonutritional indices, including the Prognostic Nutritional Index (PNI), the Controlling Nutritional Status (CONUT) score, and the C-reactive protein–albumin–lymphocyte (CALLy) index, have been proposed as markers of nutritional and inflammatory status. However, their prognostic value in elderly patients with heart failure with preserved ejection fraction (HFpEF) remains incompletely defined. This study aimed to evaluate the prognostic significance of these immunonutritional indices in elderly patients with HFpEF over a long-term follow-up period. Methods: This retrospective observational study included 200 elderly patients hospitalized with HFpEF (mean age 86.6 ± 6.5 years). Clinical, laboratory, and echocardiographic parameters were collected at admission. Nutritional status was assessed using PNI, CONUT score, and CALLy index. Patients were followed for mortality during long-term follow-up. Survival analyses were performed using Cox regression models, receiver operating characteristic (ROC) curves, and Kaplan–Meier analysis. Median follow-up was 3.8 years (IQR 2.1–5.9). Results: During follow-up, 123 patients (61.5%) died, while 77 patients (38.5%) were alive at the end of observation. In univariate analysis, PNI, CONUT score, left ventricular ejection fraction (LVEF), and the tricuspid annular plane systolic excursion to systolic pulmonary artery pressure (TAPSE/sPAP) ratio were significantly associated with mortality. In multivariate analysis, the CONUT score, LVEF, and the TAPSE/sPAP ratio remained independent predictors of mortality. ROC analysis showed strong prognostic performance for the TAPSE/sPAP ratio (AUC 0.932), CONUT score (AUC 0.925), and LVEF (AUC 0.897). Optimal cut-off values for mortality prediction were CONUT ≥ 6, LVEF ≥ 65%, and TAPSE/sPAP ≤ 0.55 mm/mmHg. Kaplan–Meier analysis confirmed significantly reduced survival among patients with higher CONUT scores, higher LVEF, and an impaired TAPSE/sPAP ratio. Conclusions: In elderly patients with HFpEF, nutritional status and cardiopulmonary functional parameters are important determinants of long-term prognosis. The CONUT score emerged as the most informative immunonutritional index, while echocardiographic parameters reflecting ventricular function and right ventricular–pulmonary arterial coupling provided additional prognostic information. Integrating nutritional assessment with echocardiographic evaluation may improve risk stratification in elderly patients with HFpEF. Full article
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27 pages, 2628 KB  
Systematic Review
Unmasking Risk in Mitral Regurgitation: Prognostic Value of Exercise Stress Echocardiography—A Systematic Review
by Andrea Sonaglioni, Massimo Baravelli, Giulio Francesco Gramaglia, Gian Luigi Nicolosi and Michele Lombardo
J. Clin. Med. 2026, 15(9), 3253; https://doi.org/10.3390/jcm15093253 - 24 Apr 2026
Viewed by 115
Abstract
Background: Risk stratification of patients with mitral regurgitation (MR), including both primary (degenerative) and secondary (functional) forms, remains challenging, particularly in asymptomatic or minimally symptomatic stages, as clinical assessment and resting echocardiography may underestimate disease severity and functional impairment. Exercise stress echocardiography (ESE) [...] Read more.
Background: Risk stratification of patients with mitral regurgitation (MR), including both primary (degenerative) and secondary (functional) forms, remains challenging, particularly in asymptomatic or minimally symptomatic stages, as clinical assessment and resting echocardiography may underestimate disease severity and functional impairment. Exercise stress echocardiography (ESE) enables dynamic evaluation of regurgitation severity, ventricular performance, and cardiopulmonary response, potentially improving prognostic assessment. Methods: A systematic review was conducted according to PRISMA guidelines. PubMed, Scopus, and EMBASE were searched from inception to March 2026. Studies including adult patients with primary or secondary MR undergoing exercise-based stress echocardiography and reporting clinical outcomes were selected. Studies using exclusively pharmacological stress were excluded. Data were qualitatively synthesized, and continuous variables were summarized as weighted medians and interquartile ranges. In addition, emerging and non-conventional prognostic markers, including anatomical indices such as the modified Haller index (MHI), were explored to provide a more comprehensive risk stratification framework. Results: Nineteen studies were included, encompassing a heterogeneous population in terms of MR etiology, severity, and clinical presentation. During follow-up, a substantial proportion of patients experienced adverse events, including heart failure, mitral valve intervention, or death. Exercise-derived parameters consistently showed strong prognostic value. In particular, exercise-induced worsening of MR severity (increase in effective regurgitant orifice area and regurgitant volume), absence of contractile reserve, elevated filling pressures (E/e’), and exercise-induced pulmonary hypertension were associated with worse outcomes. Reduced functional capacity and impaired right ventricular–pulmonary arterial coupling provided additional prognostic information. Emerging markers, including chest wall configuration assessed by MHI, appeared to further refine risk stratification in selected patient subsets. In contrast, resting parameters were less consistently predictive. Conclusions: ESE provides incremental prognostic information in patients with MR by identifying dynamic abnormalities not evident at rest. Its integration into clinical evaluation, together with novel anatomical and functional markers, may improve risk stratification and support earlier identification of high-risk patients who could benefit from timely intervention. Further studies are needed to standardize methodologies and define clinically relevant thresholds. Full article
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26 pages, 1127 KB  
Review
Redox Imbalance in the Cardiohepatic Syndrome: The Emerging Role of Oxidative Stress in Cirrhosis-Associated Cardiac Dysfunction
by Nikola Blagojevic, Dragana Blagojevic, Ana Matovic, Marko Cvrkotic, Marija Marjanovic-Haljilji, Aleksandra Sljivic, Ana Ilic, Natasa Cvetinovic, Irina Nenadic, Marko Djuric, Nemanja Dimic, Milica Aleksic, Jovana Bojicic, Aleksandra Djokovic, Snezana Lukic and Branka Filipovic
Antioxidants 2026, 15(4), 490; https://doi.org/10.3390/antiox15040490 - 15 Apr 2026
Viewed by 432
Abstract
Cirrhosis is no longer viewed solely as an isolated hepatic disorder but rather as a complex multisystemic disease that affects cardiovascular, renal, pulmonary, metabolic, and immune systems. One of its most clinically relevant but under-recognized consequences is cardiac dysfunction, manifesting as cirrhotic cardiomyopathy, [...] Read more.
Cirrhosis is no longer viewed solely as an isolated hepatic disorder but rather as a complex multisystemic disease that affects cardiovascular, renal, pulmonary, metabolic, and immune systems. One of its most clinically relevant but under-recognized consequences is cardiac dysfunction, manifesting as cirrhotic cardiomyopathy, portopulmonary hypertension, right ventricular (RV) failure, and impaired myocardial strain. Oxidative stress (OS) has recently emerged as a fundamental mechanistic link between hepatic fibrogenesis and myocardial remodeling, acting through mitochondrial injury, NADPH oxidase activation, nitric oxide dysregulation, iron-mediated ferroptosis, and inflammatory cytokines. These alterations lead to diastolic dysfunction, autonomic imbalance, myocardial fibrosis, electrophysiological abnormalities (including QTc prolongation), and impaired RV–pulmonary artery coupling. Redox biomarkers such as malondialdehyde (MDA), NOX2-derived peptides, GSH/GSSG ratio, sST2, NT-proBNP, and 8-isoprostanes hold promise in detecting early subclinical cardiac involvement in cirrhosis. Novel antioxidant therapies, including mitochondrial-targeted molecules, NOX inhibitors, and ferroptosis blockers, may improve myocardial remodeling and hemodynamic stability. This review explores the central role of redox imbalance in the cardiohepatic syndrome and its potential utility in diagnosis, monitoring, and therapy. Full article
(This article belongs to the Special Issue Roles of Oxidative Stress in Human Pathophysiology)
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15 pages, 2073 KB  
Article
Prognostic Value of the RVFWLS/PASP Ratio in Pulmonary Arterial Hypertension
by Hongjie Bian, Qinhua Zhao, Fengling Ju, Lan Wang, Yupei Han, Hongling Qiu, Cijun Luo, Pei Gang, Ke Li and Xumeng Ding
J. Cardiovasc. Dev. Dis. 2026, 13(4), 151; https://doi.org/10.3390/jcdd13040151 - 30 Mar 2026
Viewed by 386
Abstract
Background: The right ventricular free wall longitudinal strain to pulmonary arterial systolic pressure (RVFWLS/PASP) ratio is an emerging echocardiographic index for evaluating right ventricular–pulmonary artery (RV-PA) coupling. This study aimed to evaluate its prognostic significance and incremental value in risk stratification for patients [...] Read more.
Background: The right ventricular free wall longitudinal strain to pulmonary arterial systolic pressure (RVFWLS/PASP) ratio is an emerging echocardiographic index for evaluating right ventricular–pulmonary artery (RV-PA) coupling. This study aimed to evaluate its prognostic significance and incremental value in risk stratification for patients with pulmonary arterial hypertension (PAH). Methods: We conducted a retrospective–prospective cohort study of 149 adult PAH patients (87 idiopathic PAH and 62 connective tissue disease-associated PAH). RVFWLS was measured via speckle tracking echocardiography, and PASP was estimated using Doppler. The primary endpoint was event-free survival, defined as the first occurrence of all-cause mortality, lung transplantation, or rehospitalization for right heart failure. Kaplan–Meier and multivariate Cox regression analyses were performed to identify independent predictors. Results: During a median follow-up of 32 months, 78 primary events occurred. Patients in the lower RVFWLS/PASP group (<0.246%/mmHg) exhibited significantly worse exercise capacity, higher NT-proBNP levels, and poorer hemodynamics compared with the higher group (≥0.246%/mmHg) (all p < 0.001). The event-free survival rate for the composite endpoint was significantly lower in the group with reduced RVFWLS/PASP compared with that observed in the higher RVFWLS/PASP group (log-rank p < 0.05). Multivariate Cox regression analysis demonstrated RVFWLS/PASP ≥ 0.246%/mmHg was independently predictive of reduced risk for the primary endpoint (HR = 0.46, 95%CI 0.23–0.93, p < 0.05). Moreover, RVFWLS/PASP facilitated additional risk stratification among patients classified as low risk based on established models (FPHN, COMPERA 2.0, and REVEAL Lite 2). Conclusions: RVFWLS/PASP is a robust, independent determinant of long-term prognosis in patients with PAH. As a noninvasive measure of RV-PA coupling, it provides significant incremental value for clinical risk assessment and treatment monitoring. Full article
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17 pages, 840 KB  
Article
Estimated Pulse Wave Velocity as a Marker of Blood-Pressure-Dependent Arterial Load and Ventricular–Vascular Interaction in Severe Aortic Stenosis Before and After Transcatheter Aortic Valve Replacement
by Simina Mariana Moroz, Alina Gabriela Negru, Mirela Baba, Silvia Luca, Mihaela Valcovici, Alina Maria Lupu, Darius Buriman, Daniel-Dumitru Nișulescu, Ana Lascu, Daniel Florin Lighezan and Ioana Mozos
J. Cardiovasc. Dev. Dis. 2026, 13(4), 149; https://doi.org/10.3390/jcdd13040149 - 25 Mar 2026
Viewed by 423
Abstract
Background: Severe aortic stenosis (AS) increases left ventricular afterload and disrupts ventricular–vascular coupling. Transcatheter aortic valve replacement (TAVR) promptly relieves valvular obstruction, but its immediate effects on blood pressure-dependent arterial load and ventricular–vascular interactions are not fully clarified. Estimated pulse wave velocity (ePWV), [...] Read more.
Background: Severe aortic stenosis (AS) increases left ventricular afterload and disrupts ventricular–vascular coupling. Transcatheter aortic valve replacement (TAVR) promptly relieves valvular obstruction, but its immediate effects on blood pressure-dependent arterial load and ventricular–vascular interactions are not fully clarified. Estimated pulse wave velocity (ePWV), derived from age and mean arterial pressure, is a convenient surrogate of global arterial load. The study aimed to assess ePWV before and after TAVR and its relationship with ventricular function and inflammatory biomarkers. Methods: In this retrospective observational study, 100 elderly patients with severe AS undergoing TAVR underwent detailed clinical, laboratory, and echocardiographic assessments before and after the procedure. Arterial stiffness was quantified using ePWV, while left ventricular geometry and systolic function were evaluated by standard echocardiography. Post-procedural reassessment was performed at hospital discharge (median 8 days after TAVR). Results: TAVR led to a modest but significant reduction in ePWV (from 12.79 ± 1.54 to 12.39 ± 1.54 m/s, p < 0.01) and improvement in left ventricular ejection fraction (LVEF) (from 44.89 ± 9.2% to 46.7 ± 7.95%, p < 0.01). Higher baseline ePWV correlated with unfavorable left ventricular remodeling and systolic dysfunction, and post-procedural ePWV remained linked to right ventricular performance. Before TAVR, ePWV and LVEF were both associated with inflammatory biomarkers, relationships that disappeared after intervention. Conclusions: Overall, ePWV functioned as an integrated measure of ventricular–vascular interaction and global hemodynamic load, though its interpretation post-TAVR requires caution due to direct blood pressure dependence and confounding by acute procedural inflammation. Full article
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27 pages, 2553 KB  
Systematic Review
Echocardiographic Assessment of Right Ventricular–Pulmonary Arterial Coupling in Heart Failure: Prognostic Insights from a Systematic Review
by Andrea Sonaglioni, Michele Lombardo, Giulio Francesco Gramaglia, Gian Luigi Nicolosi, Alessandro Lucidi, Massimo Baravelli and Sergio Harari
J. Clin. Med. 2026, 15(6), 2334; https://doi.org/10.3390/jcm15062334 - 18 Mar 2026
Viewed by 510
Abstract
Background: Prognostic heterogeneity in heart failure (HF) is substantial and not fully captured by conventional left-sided echocardiographic parameters. Growing evidence highlights the importance of right ventricular–pulmonary arterial (RV–PA) interaction in HF pathophysiology and outcomes. The echocardiographic tricuspid annular plane systolic excursion-to-systolic pulmonary [...] Read more.
Background: Prognostic heterogeneity in heart failure (HF) is substantial and not fully captured by conventional left-sided echocardiographic parameters. Growing evidence highlights the importance of right ventricular–pulmonary arterial (RV–PA) interaction in HF pathophysiology and outcomes. The echocardiographic tricuspid annular plane systolic excursion-to-systolic pulmonary artery pressure (TAPSE/sPAP) ratio has been proposed as a simple noninvasive surrogate of RV–PA coupling, yet its prognostic value across the HF spectrum remains incompletely defined. Methods: This systematic review followed PRISMA guidelines and was registered in INPLASY. PubMed, Scopus, and EMBASE were searched from inception through January 2026 for observational studies evaluating the prognostic value of TAPSE/sPAP in adult patients with HF. Study selection, data extraction, and risk-of-bias assessment were performed independently by two reviewers. Owing to substantial heterogeneity, a qualitative synthesis with weighted pooled descriptive statistics was performed. Results: Fifteen observational studies including 5389 patients were analyzed, with a median follow-up of approximately 1.9 years, ranging from in-hospital outcomes to long-term follow-up of up to 15 years. Study populations encompassed a wide range of HF phenotypes and clinical settings, including acute and chronic HF, preserved and reduced ejection fraction, valvular heart disease, infiltrative cardiomyopathies, and advanced HF. Across studies, reduced TAPSE/sPAP was generally associated with adverse outcomes, including all-cause mortality and HF-related events, with reported hazard ratios ranging from approximately two- to five-fold. Prognostically relevant TAPSE/sPAP cut-off values tended to cluster within a relatively narrow range, with most thresholds between 0.36 and 0.40 and a weighted median of approximately 0.36. When reported, TAPSE/sPAP showed favorable discriminative performance for adverse outcomes. Overall methodological quality was predominantly fair. Conclusions: Across heterogeneous HF populations, impaired TAPSE/sPAP appears to be a consistent marker of adverse prognosis. These findings support TAPSE/sPAP as a practical, noninvasive indicator of RV–PA uncoupling that may contribute to risk stratification and phenotyping in heart failure. Prospective studies focusing on specific HF phenotypes are needed to clarify its role in longitudinal monitoring and therapeutic decision-making. Full article
(This article belongs to the Special Issue Visualizing Cardiac Function: Advances in Modern Imaging Diagnostics)
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12 pages, 920 KB  
Article
Prevalence and Prognostic Value of Right Ventricular–Pulmonary Artery Uncoupling in Adults with Right-Sided Congenital Heart Disease
by Giulia Iannaccone, Alessandro Olimpieri, Maria C. Meucci, Rosa Lillo, Maria Grandinetti, Alessio Cianci, Claudio Di Brango, Angelica B. Delogu, Massimo Massetti, Gaetano A. Lanza, Antonella Lombardo, Francesca Graziani and Francesco Burzotta
J. Pers. Med. 2026, 16(3), 164; https://doi.org/10.3390/jpm16030164 - 16 Mar 2026
Viewed by 392
Abstract
Background: Right-sided congenital heart diseases (R-CHDs) are frequently associated with right ventricular (RV) dysfunction and heterogeneous clinical trajectories, underscoring the need for individualized risk assessment. RV–pulmonary artery (RV–PA) coupling has emerged as an important prognostic marker in several cardiovascular conditions. However, its role [...] Read more.
Background: Right-sided congenital heart diseases (R-CHDs) are frequently associated with right ventricular (RV) dysfunction and heterogeneous clinical trajectories, underscoring the need for individualized risk assessment. RV–pulmonary artery (RV–PA) coupling has emerged as an important prognostic marker in several cardiovascular conditions. However, its role in adults with R-CHD has not been well established. Methods: We retrospectively reviewed consecutive adults with R-CHD evaluated at our outpatient clinic between October 2013 and November 2023. RV–PA uncoupling was defined by echocardiography as a tricuspid annular plane systolic excursion (TAPSE) to pulmonary artery systolic pressure (PASP) ratio ≤0.55. The primary composite endpoint included all-cause mortality, major supraventricular and ventricular arrhythmias, unplanned cardiac hospitalizations, and need for (re)-interventions. Results: A total of 132 patients (mean age 41.6 ± 15.7 years; 51.5% male) were included. RV–PA uncoupling was identified in 48 patients (36.4%). Over a median follow-up of 40.3 months, the primary composite endpoint occurred in 71 patients (53.8%). Patients experiencing adverse outcomes were older and showed lower TAPSE, higher PASP, larger RV and right atrial dimensions, and a significantly higher prevalence of RV–PA uncoupling (p < 0.001). Multivariable Cox regression analysis demonstrated that RV–PA uncoupling was a strong independent predictor of adverse outcomes (HR 4.478, p < 0.001), outperforming its individual components. In addition, RV–PA uncoupling and RV mid-diameter independently predicted the need for surgical or interventional procedures during follow-up. Conclusions: RV–PA uncoupling provides robust and independent prognostic information in adults with R-CHD and represents a practical tool for personalized risk stratification, potentially guiding tailored surveillance strategies and timing of therapeutic interventions. Full article
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18 pages, 675 KB  
Article
Prognostic Value of Non-Invasively Determined Right Ventricular–Arterial Coupling Surrogate Parameters in Patients with Dilated Cardiomyopathy
by Maria Iovănescu, Diana-Ruxandra Hădăreanu, Despina Toader, Oana Munteanu-Mirea and Ionuț Donoiu
J. Clin. Med. 2026, 15(6), 2239; https://doi.org/10.3390/jcm15062239 - 16 Mar 2026
Viewed by 399
Abstract
Background/Objectives: Right ventricular dysfunction is frequent in patients with dilated cardiomyopathy (DCM) and contributes significantly to prognosis. This study evaluated the prognostic value of echocardiography-determined surrogate parameters of right ventricular–arterial (RV–PA) coupling in patients with DCM. Methods: A total of 88 [...] Read more.
Background/Objectives: Right ventricular dysfunction is frequent in patients with dilated cardiomyopathy (DCM) and contributes significantly to prognosis. This study evaluated the prognostic value of echocardiography-determined surrogate parameters of right ventricular–arterial (RV–PA) coupling in patients with DCM. Methods: A total of 88 patients admitted between January 2019 to September 2023 were retrospectively and prospectively assessed and followed for a mean of 14 months. The primary endpoint was rehospitalization for decompensated heart failure (HF); the secondary endpoint was all-cause mortality. The parameters studied included TAPSE/PASP, RVFAC/PASP, RVFWLS/PASP, and RVEF/PASP. Results: In univariate analysis, all indices were associated with rehospitalization, but multivariate analysis retained only RVFWLS/PASP and RVEF/PASP as independent predictors. Optimal cut-offs were identified as 1.2 for RVEF/PASP (sensitivity 72%, specificity 80%) and 0.46 for RVFWLS/PASP (sensitivity 72%, specificity 76%). None of the parameters correlated significantly with all-cause mortality. Conclusions: These findings highlight the prognostic utility of non-invasively derived RV–PA coupling indices for rehospitalization risk stratification in DCM. Full article
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18 pages, 1559 KB  
Review
Stress Echocardiography in the Diagnosis and Evaluation of Pulmonary Hypertension: Practical Recommendations, Haemodynamic Phenotyping, and Application in Adults and Children
by Dafni Charisopoulou, George Koulaouzidis, Panagiota Kleitsioti, Nikolaos Antoniou, Christos Mantzios, Orestis Grammenos and Sotiria Iliopoulou
Diagnostics 2026, 16(5), 792; https://doi.org/10.3390/diagnostics16050792 - 6 Mar 2026
Viewed by 755
Abstract
Pulmonary hypertension (PH) is a complex condition in which early diagnosis remains challenging, particularly in patients with exertional symptoms and normal or borderline resting haemodynamics. Although right heart catheterisation is the diagnostic gold standard, transthoracic echocardiography is the recommended first-line non-invasive test. However, [...] Read more.
Pulmonary hypertension (PH) is a complex condition in which early diagnosis remains challenging, particularly in patients with exertional symptoms and normal or borderline resting haemodynamics. Although right heart catheterisation is the diagnostic gold standard, transthoracic echocardiography is the recommended first-line non-invasive test. However, resting echocardiography provides only a static assessment and may underestimate disease severity in early or latent pulmonary vascular disease due to preserved pulmonary vascular compliance and adaptive right ventricular responses. Because pulmonary haemodynamics are intrinsically flow-dependent, pathological abnormalities may only emerge during increased cardiac output. Stress echocardiography, performed using exercise or pharmacological stress, enables dynamic evaluation of pulmonary pressure responses, cardiac output augmentation, right ventricular contractile reserve, and ventricular interaction. Increasing evidence indicates that stress echocardiography can unmask abnormal pulmonary pressure–flow relationships, impaired pulmonary vascular reserve, and reduced right ventricular–pulmonary arterial coupling that are not apparent at rest, thereby improving functional and haemodynamic characterisation in selected patients. This Diagnostic Review outlines the physiological basis for stress echocardiographic assessment of pulmonary circulation, proposes practical recommendations for patient selection and testing protocols, and provides a framework for interpretation centered on pressure–flow relationships rather than absolute pulmonary pressure thresholds. Particular attention is given to clinical scenarios with high diagnostic yield, including unexplained exertional dyspnoea, systemic sclerosis, suspected heart failure with preserved ejection fraction, at-risk relatives of patients with pulmonary arterial hypertension, selected athletes, and paediatric populations. Stress echocardiography should not be considered a standalone diagnostic test for PH but, when performed in experienced centers and integrated within structured diagnostic pathways, it represents a valuable non-invasive adjunct to guide referral for invasive haemodynamic confirmation. Full article
(This article belongs to the Special Issue Beyond the Image: Cardiac Imaging at the Service of the Patient)
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16 pages, 543 KB  
Review
Pleiotropic Effects of Cardiac Resynchronization Therapy on Cardiometabolic Modulation in Heart Failure
by Panagiotis Theofilis, Panagiotis Iliakis, Aikaterini-Eleftheria Karanikola, Michail Botis, Kyriaki Mavromoustakou, Panagiotis Xydis, Nikolaos Ktenopoulos, Paschalis Karakasis, Ioannis Leontsinis, Christina Chrysohoou and Konstantinos Tsioufis
Medicina 2026, 62(3), 465; https://doi.org/10.3390/medicina62030465 - 28 Feb 2026
Viewed by 540
Abstract
Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency [...] Read more.
Cardiac resynchronization therapy (CRT) is a cornerstone intervention for patients with heart failure (HF) and electrical dyssynchrony, improving quality of life, functional capacity, and survival. Beyond mechanical synchrony, mounting evidence suggests CRT exerts systemic and myocardial cardiometabolic benefits. CRT acutely enhances mechanical efficiency and shifts substrate utilization toward greater oxidation of fatty acids and ketones, effects that correlate with long-term reverse remodeling on cardiac magnetic resonance imaging. Earlier metabolomic profiling demonstrated that CRT normalizes circulating energy metabolites, improving Krebs cycle intermediates and substrate balance between glucose and lipids, while baseline metabolite patterns may differentiate responders from non-responders. These metabolic adaptations accompany favorable changes in diastolic performance, right ventricular function, and ventriculo-arterial coupling. In parallel, improved splanchnic perfusion and reduced congestion may ameliorate gut dysbiosis and endotoxemia, mitigating systemic inflammation. Collectively, these findings position CRT as a therapy capable of both mechanical and metabolic restoration in advanced HF. In this review, we discuss the emerging data on how CRT reconditions myocardial energy metabolism, influences ventricular–arterial interactions, and modulates peripheral and gut-derived metabolic pathways. Full article
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12 pages, 826 KB  
Article
External Validation of Two Different Cardiac Damage Staging Systems for Aortic Stenosis in Patients Treated with Surgical Aortic Valve Replacement
by Carlos Gil, Carmen Olmos, Patrick O’Neill, Ricardo Román, Manuel Carnero, Daniel Pérez-Camargo, Lourdes Montero, María Rivadeneira, Sandra Gil-Abizanda, Eduardo Pozo and Fabián Islas
J. Clin. Med. 2026, 15(5), 1795; https://doi.org/10.3390/jcm15051795 - 27 Feb 2026
Viewed by 299
Abstract
Background: Several cardiac damage staging systems for aortic stenosis (AS) have been proposed, but their usefulness in patients undergoing surgical aortic valve replacement (SAVR) remains unknown. Objectives: We aim to externally validate two staging systems in patients who underwent SAVR. Methods [...] Read more.
Background: Several cardiac damage staging systems for aortic stenosis (AS) have been proposed, but their usefulness in patients undergoing surgical aortic valve replacement (SAVR) remains unknown. Objectives: We aim to externally validate two staging systems in patients who underwent SAVR. Methods: Single-centre prospective cohort of patients treated with SAVR (2017–2022). Based on baseline echocardiographic parameters, patients were classified into the different stages of two published staging systems (Généreux et al. and Gutiérrez et al.), and the discriminatory yield of these systems for 1-year mortality was evaluated. Results: In total, 350 patients were analysed (mean age 69 (9.4) years, 37.8% were female). The median EuroSCORE II was 1.7 (1.1–3.1), and 1-year mortality occurred in 17 (4.8%) patients. The staging system developed by Gutiérrez et al. had an area under the ROC curve (AUC) of 0.687 (95% CI: 0.571–0.803) and was superior to Généreux et al.’s system (AUC of 0.554; 95% CI: 0.439–0.669; p = 0.008). Applying Gutiérrez et al.’s system, 1-year mortality rates progressively increased with higher damage staging: 1.9% (2/103) for Stage 0; 5.1% (5/175) for Stage 1; 12.5% (5/40) for Stage 2; and 15.6% (5/32) for Stage 3 (which represents right-sided damage measured by right ventricular–arterial coupling (RVAc); p= 0.038). No significant differences in outcomes between stages were found when using the staging proposed by Généreux et al. (p = 0.218). Conclusions: In a surgical cohort of patients with AS, a cardiac staging system that included RVAc showed greater discriminatory power for 1-year mortality. Assessing the interrelation between right ventricular function and afterload could help in better risk stratification in this context. Full article
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16 pages, 1626 KB  
Article
Evolution of Cardiac Damage Across Clinically Defined Stages of Aortic Stenosis in Patients Undergoing TAVR: A Single-Center Retrospective Cohort Study
by María Rivadeneira-Ruiz, Carmen Olmos, Sandra Gil-Abizanda, Pilar Jiménez-Quevedo, Eduardo Pozo-Osinalde, Luis Nombela-Franco, José Alberto de Agustín and Fabián Islas
J. Clin. Med. 2026, 15(4), 1575; https://doi.org/10.3390/jcm15041575 - 17 Feb 2026
Viewed by 384
Abstract
Background: Echocardiography is essential for diagnosing and guiding therapy in aortic stenosis (AS). Cardiac damage staging systems may better characterize myocardial and extracardiac involvement. We aim to evaluate the presence and progression of cardiac damage across the clinical course of AS. Methods: A [...] Read more.
Background: Echocardiography is essential for diagnosing and guiding therapy in aortic stenosis (AS). Cardiac damage staging systems may better characterize myocardial and extracardiac involvement. We aim to evaluate the presence and progression of cardiac damage across the clinical course of AS. Methods: A single-center retrospective cohort study was conducted, which included consecutive patients who ultimately underwent TAVR and had retrievable serial echocardiograms at moderate AS, first severe AS, and pre-TAVR symptomatic severe AS (2017–2021). A total of 179 patients were evaluated (mean age 82.7 [5.9] years at moderate AS; 46% male, p = 0.27). Cardiac damage was classified according to two established staging systems. Results: The median time from moderate to severe AS was 32 months (IQR 18–48). Most echocardiographic parameters deteriorated primarily at symptom onset, whereas moderate AS and first severe (asymptomatic) AS showed broadly similar profiles. However, left ventricular global longitudinal strain (LV GLS) was already impaired at the first severe stage, and right ventricular–arterial coupling (RVAc, TAPSE/sPAP) progressively worsened as AS advanced to the severe stage, independently of symptom status (LV GLS −18.1%, n = 163; −17.1%, n = 143; and −14.9%, n = 143; RVAc 1.0, n = 131; 0.8, n = 130; and 0.7, n = 130), respectively; overall p < 0.05. Both staging systems demonstrated increasing cardiac damage with AS progression. Conclusions: Cardiac damage may occur early in AS. The marked deterioration at symptom onset underscores the importance of systematic myocardial assessment and supports prospective studies to evaluate whether integrating LV GLS and RVAc as sensitive early markers of disease progression improves risk stratification. Full article
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25 pages, 4813 KB  
Article
Cardiac and Vascular Adaptation During Pregnancy in Asian and Caucasian Women: Insights from a Prospective Cohort Study
by Andrea Sonaglioni, Irene Sutti, Giuditta Ferrara, Marta Ruggiero, Giovanna Margola, Gian Luigi Nicolosi, Stefano Bianchi, Michele Lombardo and Massimo Baravelli
J. Clin. Med. 2026, 15(2), 756; https://doi.org/10.3390/jcm15020756 - 16 Jan 2026
Cited by 1 | Viewed by 423
Abstract
Background/Objectives: Ethnicity is associated with differences in cardiac structure and function in non-pregnant populations, but pregnancy-specific data—particularly for myocardial deformation—remain limited. We investigated whether ethnicity influences cardiac geometry, biventricular and biatrial mechanics, hemodynamics, and carotid vascular indices in healthy women during the third [...] Read more.
Background/Objectives: Ethnicity is associated with differences in cardiac structure and function in non-pregnant populations, but pregnancy-specific data—particularly for myocardial deformation—remain limited. We investigated whether ethnicity influences cardiac geometry, biventricular and biatrial mechanics, hemodynamics, and carotid vascular indices in healthy women during the third trimester of pregnancy. Methods: In this prospective, monocentric study, 80 healthy women with singleton third-trimester pregnancies were enrolled, including 40 Asian and 40 Caucasian women matched for age and body mass index. All participants underwent standardized clinical and laboratory evaluation, comprehensive transthoracic echocardiography with Doppler, speckle-tracking analysis of both ventricles and atria, and bilateral carotid ultrasonography. Logistic regression analyses were performed in Asian women to identify correlates of supranormal left ventricular ejection fraction (LVEF ≥ 70%) and enhanced left ventricular global longitudinal strain (LV-GLS > 20%). Results: Age and gestational age were similar between groups, whereas body surface area was lower in Asian women (1.65 ± 0.12 vs. 1.77 ± 0.15 m2, p < 0.001). Asian women exhibited smaller left ventricular dimensions and volumes but higher LVEF (median 71.6% vs. 66.4%, p < 0.001). Heart rate and blood pressure were comparable, whereas stroke volume [45.5 ± 9.6 vs. 68.0 (48.9–110) mL, p < 0.001] and cardiac output (3.9 ± 0.9 vs. 4.9 ± 0.8 L/min, p < 0.001) were lower in Asian women, who also demonstrated higher total peripheral resistance and lower ventricular–arterial coupling (0.31 ± 0.09 vs. 0.37 ± 0.07, p = 0.001). Speckle-tracking echocardiography revealed higher LV-GLS (21.9 ± 1.9% vs. 20.5 ± 2.0%, p = 0.002), higher LV global circumferential strain, enhanced right ventricular longitudinal strain, and higher reservoir strain of both atria in Asian women. Carotid ultrasonography showed smaller common carotid diameter and cross-sectional area in Asian women (10.7 ± 2.5 vs. 13.7 ± 2.3 mm2, p < 0.001). In regression analyses, supranormal LVEF was independently associated with smaller LV end-diastolic diameter (OR 0.39, 95% CI 0.16–0.97), while enhanced LV-GLS was independently associated with lower neutrophil-to-lymphocyte ratio (OR 0.04, 95% CI 0.00–0.87). Conclusions: Ethnicity is associated with multidimensional differences in cardiac geometry, myocardial mechanics, vascular load, and carotid structure in healthy third-trimester pregnancy. Ethnicity-aware interpretation and tailored reference ranges may improve the accuracy of echocardiographic assessment during late gestation. Full article
(This article belongs to the Section Cardiology)
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13 pages, 460 KB  
Review
Right Ventricular–Pulmonary Artery Coupling as a Prognostic Marker in Cardiac Amyloidosis: A Comprehensive Review
by Nikolaos Tsiamis, Dimitrios Afendoulis, Christos Tountas, Fotios Toulgaridis, Flora Tsakirian, Sotirios Tsalamandris, Maria Drakopoulou, Kostas Tsioufis, Anastasia Kitsiou and Konstantinos Toutouzas
Life 2026, 16(1), 109; https://doi.org/10.3390/life16010109 - 12 Jan 2026
Viewed by 1117
Abstract
Background: Cardiac amyloidosis (CA) is characterized by progressive myocardial infiltration leading to restrictive cardiomyopathy and heart failure. While left ventricular assessment has traditionally dominated prognostic evaluation, right ventricular (RV) dysfunction and RV–pulmonary artery (PA) coupling have emerged as critical determinants of outcomes. Objectives: [...] Read more.
Background: Cardiac amyloidosis (CA) is characterized by progressive myocardial infiltration leading to restrictive cardiomyopathy and heart failure. While left ventricular assessment has traditionally dominated prognostic evaluation, right ventricular (RV) dysfunction and RV–pulmonary artery (PA) coupling have emerged as critical determinants of outcomes. Objectives: This review synthesizes current evidence on RV–PA coupling as a prognostic marker in cardiac amyloidosis, examining measurement methodologies, prognostic significance, pathophysiological mechanisms, and clinical applications. Methods: We comprehensively reviewed the recent literature on RV–PA coupling in CA, focusing on studies published from 2020 to 2025, including both AL and ATTR subtypes. We analyzed data from multicenter cohorts, prospective registries, and validation studies examining the relationship between RV–PA coupling indices and clinical outcomes. Results: RV–PA coupling, most commonly assessed using the tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP) ratio, consistently demonstrates strong independent prognostic value for mortality and heart failure outcomes in CA patients. Impaired coupling (TAPSE/PASP < 0.45 mm/mmHg) identifies high-risk patients with hazard ratios ranging from 1.98 to 4.17 for adverse outcomes. In a multicenter cohort of 283 patients, TAPSE/PASP < 0.45 mm/mmHg was independently associated with death or heart failure hospitalization (HR 1.98, 95% CI 1.32–2.96, p = 0.001) and significantly improved risk reclassification (NRI 0.46–0.49). In ATTR-specific populations receiving disease-modifying therapy, impaired coupling (TAPSE/PASP ≤ 0.382 mm/mmHg) predicted three-year mortality with an adjusted HR of 2.99. The coupling index provides incremental value over individual RV parameters by accounting for afterload conditions and demonstrates consistent prognostic performance across both AL and ATTR subtypes. Conclusions: RV–PA coupling represents a robust, easily obtainable prognostic marker that should be routinely assessed in CA patients for risk stratification and clinical decision-making. The TAPSE/PASP ratio can be calculated from standard echocardiographic examinations without additional cost or time, making it practical for widespread implementation. Future research should focus on standardizing measurement protocols, establishing disease-specific thresholds, evaluating coupling trajectories with novel therapies, and integrating coupling assessment into staging systems and management algorithms. The strong prognostic signal, pathophysiological relevance, and ease of measurement position RV–PA coupling as an essential component of comprehensive cardiac amyloidosis evaluation. Full article
(This article belongs to the Special Issue Innovation and Translation in Cardiovascular Interventions)
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