Search Results (94)

Objectives: Connective tissue dysplasia (CTD) is associated with disorders of collagen synthesis and is widely spread among the healthy population and people with disabilities. In the heart, primarily in the left ventricle (LV), CTD manifests itself as the formation of false tendons (LVFTs) to maintain close-to-normal LV pump function. This exploratory work is devoted to the search for general patterns of cardiac response to physical activity in athletes with disabilities, CTD, and LVFTs. The extent to which “the type of sports or the type of disability” determines the involvement of the heart’s functional reserve is the main testable question of the proposed research. Methods: The group under this study included 610 individuals with disabilities aged from 6 to 60 years with at least two transverse and/or oblique FTs per LV. Participants represented different sports disciplines (n = 10) and various forms of disabilities (n = 4). Cardiovascular indicators were obtained by means of standard TTE, impedance cardiography for hemodynamic monitoring in active orthotest, resting, and stress 12-lead ECG. Exercise testing of the athletes was performed with the use of appropriate methods of physical loading. In total, 141 parameters of cardiorespiratory function and exercise performance per participant were recorded. Statistical analysis of the dataset obtained across sports types or disability types was performed using one-way ANOVA or the Kruskal-Wallis test, depending on the assumptions of normality and homogeneity of variance. Results: Most importantly, it was found that only maximum relative oxygen consumption (VO₂max, mL·kg⁻¹·min⁻¹) as a reliable indicator of the heart’s functional reserve and the corrected QT (QTc, ms) interval as an integral measure of the heart’s electrical activity demonstrated statistically significant differences across the sports specialization or the disability type. In particular, significance values (P) for VO₂max across athletic disciplines and nosology categories were equal to 0.00063 and 0.01028 (one-way ANOVA), while for QTc they were 0.00001 and 0.02185 (Kruskal-Wallis), respectively. Furthermore, the type of disability had a lower impact on VO₂max and QTc than the type of athletic activity. Conclusions: In athletes with disabilities and CTD, sport specialization may involve the heart’s functional reserve to a greater extent than the type of disability. To prescribe training loads for people with disabilities and CTD, individual cardiology screening with an emphasis on VO₂max and QTc is necessary. Full article

Mitochondria serve as an essential component in the maintenance of cardiac function, and targeting them may represent a promising approach to handling heart failure (HF). HF in this review refers to various etiologies, including ischemic cardiomyopathy, dilated cardiomyopathy, and hypertrophic cardiomyopathy, unless otherwise specified. Mitochondrial dysfunction, a distinctive feature of HF, leads to a progressive decrease in bioenergetic reserves due to switching of energy production from oxidation of fatty acids in mitochondria to glycolytic pathways. The main problem in developing methods to improve mitochondrial function lies in the fact that protein preparations injected through the bloodstream cannot enter cells through the plasma membrane. Modern gene therapy involving the delivery of missing genes to cells using adeno-associated virus (AAV) vectors has the potential to improve the function of cardiomyocytes (CMCs). This type of therapy aims to target proteins that have been lost, damaged, or altered due to pathological conditions in the myocardium. This review summarizes pathophysiological mechanisms associated with mitochondrial dysfunction, which is mainly caused by increased oxidative stress and impaired mitochondrial biodynamics under HF progression. It also addresses possible ways to modulate these processes using gene therapy. Special attention is paid to modern characteristics of AAVs that can be used as vectors for the efficient delivery of desired genes to CMCs. Full article

Coronary artery disease (CAD) remains the leading cause of cardiovascular mortality worldwide. Accurate and non-invasive quantification of coronary hemodynamics, namely in the right coronary artery (RCA), is essential for clinical decision-making but remains challenging due to the complex interaction among vessel geometry, pulsatile flow, and blood rheology. This study presents and validates a transparent computational framework for non-invasive fractional flow reserve (FFR) estimation using patient-specific RCA geometries reconstructed from coronary computed tomography angiography (CCTA) using SimVascular 27-03-2023. The proposed workflow integrates realistic boundary conditions through a Womersley velocity profile and a three-element Windkessel outlet model, coupled with a viscoelastic blood rheology formulation (sPTT) implemented via user-defined functions (UDFs). This work integrates all clinically relevant conditions of invasive FFR assessment into a single patient-specific computational framework, while delivering results within a time frame compatible with clinical practice, representing a meaningful methodological advance. The methodology was applied to seven patient-specific cases, and the resulting non-invasive FFR values were compared with both invasive wire-based measurements and commercial HeartFlow^® outputs (Mountain View, CA, USA). Under hyperemic conditions, the computed FFR values showed strong agreement with invasive references, with a mean relative error of 8.4% ± 6.3%, showing diagnostic consistency similar to that of HeartFlow^® (8.3% ± 8.1%) for the selected dataset. These findings demonstrate the ability of the proposed CFD-based pipeline to accurately replicate physiological coronary behavior under hyperemia. This novel workflow provides a fully on-site, open-source, reproducible, and cost-effective framework. Ultimately, this study advances the clinical applicability of non-invasive CFD tools for the functional assessment of CAD, particularly in the RCA. Full article

Heart failure (HF) remains a major cause of morbidity and mortality worldwide, with its prevalence continuing to rise due to an aging population and the increasing burden of cardiometabolic diseases. Advances in understanding HF pathophysiology—neurohormonal, inflammatory, and metabolic mechanisms—have led to significant improvements in diagnosis and management, emphasizing earlier detection and patient-centered approaches. Novel biomarkers have the potential to enhance risk assessment beyond traditional natriuretic peptides. Imaging advances can enhance structural and functional assessment, enabling more accurate phenotyping, disease characterization, and risk stratification. Recent advances and real-world data have been used to implement and optimize guideline-directed medical therapy (GDMT) for HF to reduce HF hospitalizations and cardiovascular mortality across the spectrum of HF etiologies. Adjunctive therapies are reserved for select patients with persistent symptoms or high-risk features despite optimal GDMT. Device- and transcatheter-based interventions include established and emerging technologies that address persistent symptoms, structural abnormalities, and hemodynamic abnormalities despite optimal GDMT, thereby expanding treatment options for high-risk patients. Collectively, these advancements highlight a paradigm shift toward precise, personalized approaches to HF management, thereby improving long-term outcomes across the spectrum of HF etiologies. Full article

Background/Objectives: Frailty, a syndrome characterized by diminished physiological reserves and increased vulnerability to stressors, is a strong predictor of adverse outcomes in heart failure. The MECKI (Metabolic Exercise Cardiac Kidney Index) score, derived from cardiopulmonary exercise testing and renal function parameters, has demonstrated prognostic value in HF patients. This study aimed to evaluate the prognostic value of physical frailty on mortality in patients with advanced heart failure and to compare it directly with the MECKI score. Methods: A total of 104 patients with advanced HF receiving optimized guideline-directed medical therapy were prospectively enrolled. At baseline, all patients underwent clinical, echocardiographic, and laboratory assessment and CPET for MECKI score calculation. Physical frailty was assessed using a modified Fried phenotype tailored for HF. The composite endpoint comprised all-cause mortality, urgent heart transplantation, or LVAD implantation. Results: Over a mean follow-up of 30.0 ± 15.3 months, there were 25 deaths, 5 urgent heart transplants, and 1 LVAD implantation. Patients who experienced the composite outcome had significantly worse NYHA class, higher NT-proBNP, lower VO₂max, higher VE/VCO₂ slope, higher frailty, and higher MECKI score (all p < 0.001). Frailty was significantly correlated with all MECKI score components, as demonstrated by Spearman’s rank correlation analysis. Both frailty (HR = 1.89; 95% CI 1.22–2.93; p = 0.005) and MECKI score (HR = 1.04; 95% CI 1.00–1.08; p = 0.037) independently predicted outcomes. ROC analysis showed high and comparable discriminative performance (AUC = 0.86 for frailty; AUC = 0.88 for MECKI). Conclusions: Physical frailty and MECKI scores independently predict mortality and adverse events in advanced HF. Physical frailty, despite its simplicity and low cost, provides prognostic insight comparable to the MECKI score and may represent a practical alternative when CPET is unavailable. Full article

Background/Objectives: The diagnosis and risk stratification of valvular heart disease have traditionally relied on resting echocardiography. However, in a significant portion of patients, resting findings do not fully reflect the hemodynamic severity of the condition, particularly in asymptomatic individuals with severe valvular disease or those with nonspecific symptoms. In this context, stress echocardiography emerges as a vital imaging modality, providing a dynamic assessment of valvular, ventricular, and pulmonary function under hemodynamic load (from physical exercise or pharmacological agents). Methods: We conducted a comprehensive synthesis and critical evaluation of the current landscape, recent advancements, and future directions regarding the application of stress echocardiography in valvular heart disease. Results: This comprehensive review explores the incremental role of stress echocardiography in valvular heart disease, analyzing the evolution of its clinical applications, from low-flow, low-gradient aortic stenosis to the evaluation of contractile reserve and exercise-induced pulmonary hypertension in mitral stenosis and regurgitation. We discuss standardized protocols, key parameters to monitor, and the diagnostic and prognostic outcomes from major clinical trials and current guidelines. Attention is given to stress echocardiography’s ability to unmask the true severity of the disease and to identify patients at high risk for adverse events, thereby guiding crucial clinical decisions, such as the optimal timing for surgical or transcatheter intervention. Conclusions: The review evaluates the limitations of modality and outlines future research directions, including its integration with new technologies like 3D echocardiography and speckle tracking techniques, to further optimize the role of stress echocardiography as a decision-making tool in the multidisciplinary management of valvular heart disease. Full article

Severe aortic stenosis represents a significant prognostic burden, particularly in symptomatic patients. The advent of transcatheter aortic valve replacement (TAVR) has revolutionized the treatment of patients previously considered ineligible for surgical aortic valve replacement (SAVR). TAVR provides a relatively safe intervention that leads to improvements in survival, symptoms, and functional status within months of implantation. A major complication following TAVR is the occurrence of paravalvular leaks (PVLs), which have been associated with increased mortality and higher rates of heart failure-related hospitalizations. PVLs refer to abnormal blood flow between the implanted valve and the aortic wall, which can compromise the functionality of the device. Careful pre-procedural planning enables the identification of patients at higher risk for PVL development. Although the incidence of PVLs has decreased with the introduction of newer-generation transcatheter valves, the condition remains clinically relevant. Due to the complex anatomy of the aortic valve apparatus and interference from the prosthetic frame, accurate evaluation of PVLs requires a multimodal diagnostic approach. Current evidence on PVL management is limited. In most cases, a conservative approach is adopted, while interventional strategies (such as pre- and post-dilatation, percutaneous PVL closure, and TAVR-in-TAVR) are reserved for selected patients. We performed a systematic literature review to summarize the incidence, predictors, diagnostic techniques, and management strategies of PVLs following TAVR. Full article

Background: Orthotopic heart transplantation (OHT) remains the gold standard for end-stage heart failure, yet individualized risk assessment for postoperative mortality remains challenging. We aimed to develop and interpret random forest-based models for predicting 30-day and 1-year mortality and to examine whether the key predictors differ between the 30-day and 1-year models. Methods: We analyzed 581 patients who underwent OHT between 2012 and 2024. The 30-day and 1-year mortality rates were 9.9% and 17.6%, respectively. Eighty-seven preoperative and forty-eight postoperative variables were considered as input features for model development. Random forest models were trained and validated using five-fold cross-validation, and explainability was assessed using SHapley Additive exPlanations (SHAP). Results: Using preoperative features only, the random forest models achieved AUCs of 0.62 (95% CI, 0.48–0.75) for 30-day and 0.67 (95% CI, 0.56–0.78) for 1-year mortality. SHAP analysis revealed that early mortality predictions were primarily driven by features reflecting acute physiological stress—hepatic dysfunction, inflammation, and hemodynamic instability—whereas long-term predictions were increasingly influenced by renal function, metabolic reserve, and frailty. Incorporating postoperative features improved performance (AUC 0.98 [95% CI, 0.97–0.99] and 0.86 [95% CI, 0.80–0.92], respectively), with model predictions dominated by the severity and persistence of organ dysfunction: short-term risk driven by hepatic injury, hemodynamic compromise, and critical illness, and long-term risk by sustained hepatic and renal impairment, metabolic resilience, and duration of circulatory support. Conclusions: Random forest models integrating preoperative and immediate postoperative data could predict short- and mid-term mortality after OHT. SHAP analysis demonstrated temporal shifts in the most important predictors, supporting the role of dynamic, data-driven risk assessment in transplant care. Full article

Background/Objectives: Cancer Therapy-Related Cardiac Dysfunction (CTRCD) is a major complication in patients with non-Hodgkin lymphoma (NHL), potentially leading to heart failure and other severe cardiovascular events. Early identification of patients at risk is crucial for timely interventions. Methods: A prospective analytical cohort study was conducted on 127 adult NHL patients to evaluate chemotherapy-related cardiac dysfunction over a 6-month period, with the aim of assessing early adverse cardiac effects. Assessments included echocardiography, cardiorespiratory exercise testing, 24-h Holter monitoring, and measurement of cardiac-specific biomarkers (troponin I and NT-proBNP) to identify early subclinical cardiac changes. Results: A predictive model for CTRCD was developed using clinical, serological, echocardiographic, cardiopulmonary, and treatment-related parameters in patients with non-Hodgkin lymphoma. The model demonstrated high overall accuracy (94.2%) and strong discriminative ability (AUC 0.95; precision-sensitivity AUC 0.824) for 6-month cardiotoxicity. SHAP analysis identified the most influential predictors as baseline SDNNi, mean daily heart rate, total doxorubicin dose, NT-proBNP, QT corrected interval, hemoglobin, age, left atrial volume, and diastolic function indices (E/e′, E/A). Lower cardiopulmonary reserve was also associated with increased risk. Conclusions: The predictive model developed in this study serves as a practical and robust tool for assessing the risk of cancer therapy-related cardiac dysfunction. Full article

The prevalence of advanced heart failure (AdHF) is increasing globally, driven by population aging and improved survival rates in chronic heart failure (CHF). Durable Mechanical Circulatory Support (DMCS), particularly Left Ventricular Assist Devices (LVADs), has become a cornerstone in AdHF management. However, its successful implantation requires a comprehensive preoperative evaluation integrating cardiac, hemodynamic, and systemic assessments. Echocardiography and cardiac magnetic resonance (CMR) provide critical data for risk stratification—e.g., LV ejection fraction < 25%, LV end-diastolic diameter < 60 mm, or free wall RV longitudinal strain (fwRVLS) > −14% predict poorer outcomes. Right heart catheterization (RHC) identifies hemodynamic contraindications (PVR > 6 WU, PAPi < 1.5, cardiac index < 2 L/min/m²), while cardiopulmonary exercise testing (CPET) remains pivotal for assessing functional reserve (peak VO₂ < 12 mL/kg/min or <50% predicted). Systemic assessment must address renal, hepatic, oncologic, and psychiatric comorbidities that influence surgical risk. Integrating these multimodal data within a multidisciplinary framework—spanning cardiologists, cardiac surgeons, anesthesiologists, and psychologists—optimizes selection and outcomes for DMCS candidates. Full article

The relationship of diabetes mellitus (DM) with cardiovascular mortality and morbidity has been widely established. Diabetic cardiomyopathy (DBCM) has been increasingly recognized as the development of cardiac dysfunction accompanied by heart failure (HF) symptoms in the absence of obvious causes like coronary artery disease (CAD), hypertension (HTN) or valvular diseases. The objective of this review is to critically appraise the role of echocardiography in the diagnosis and prognostic stratification of DBCM. Echocardiography remains the first-line imaging modality due to its availability, repeatability, non-invasive nature and ability to assess structural and functional changes. Classical echocardiographic indices such as left ventricular hypertrophy and systolic and diastolic dysfunction assessment provide valuable information but they lack sensitivity, often remaining normal until advanced stages of DBCM. Recently developed echocardiographic modalities, including strain imaging, myocardial work indices and left atrial strain, may allow for earlier detection of subclinical myocardial dysfunction, having important prognostic implications. However, these advanced modalities require high imaging quality, expertise and standardization, being subject to technical and physio-logical limitations. Stress echocardiography, particularly exercise-based protocols, is an increasingly recognized, valuable tool for unmasking exertional abnormalities in filling pressures, myocardial reserve and pulmonary pressures that are not evident at rest. Until now, stress echocardiography requires validation in large cohorts to assess its prognostic power. This review highlights the importance of timely recognition of DBCM, underscores the advantages and disadvantages of current echocardiographic approaches and outlines future perspectives in multimodality imaging to improve patient outcomes. Full article

Purpose: While peak oxygen uptake ($\stackrel{.}{\mathrm{V}}$O_2peak) is the gold standard method for assessing exercise tolerance, there is a tendency for underestimation. Several other cardiopulmonary exercise testing (CPET) variables may provide additive prognostic value beyond $\stackrel{.}{\mathrm{V}}$O_2peak alone. The aim of this study was to examine if alternative CPET indices of exercise tolerance are (a) impaired in people with T2D and (b) independently associated with measures of cardiovascular structure and function measured via echocardiography and cardiac MRI. Methods: Participants with type 2 diabetes (T2D) and healthy controls underwent cardiac magnetic resonance imaging, transthoracic echocardiography, and a CPET. Multiple linear regression was used to determine the relationship between indices of exercise tolerance and markers of cardiovascular structure and function. Results: A total of 84 people with T2D and 36 healthy volunteers were included in the analysis. All CPET outcomes were worse in those with T2D vs. the controls. Three CPET outcomes were associated with markers of cardiovascular structure and function: $\stackrel{.}{\mathrm{V}}$O₂ recovery with mean aortic distensibility (β = 0.218, p = 0.049); heart rate recovery with early filling velocity on transmitral Doppler/early relaxation velocity (β = −0.270, p = 0.024), left ventricular mass/volume ratio (β = −0.248, p = 0.030) and mean aortic distensibility (β = 0.222, p = 0.029); and $\stackrel{.}{\mathrm{V}}$O₂ at the ventilatory threshold with myocardial perfusion reserve (β = 0.273, p = 0.018). Perspective: These lesser-used CPET indices could be used to identify which people with T2D are at elevated risk of progression to symptomatic heart failure. However, larger longitudinal studies are required to confirm these findings and their potential clinical application. Full article

Transient receptor potential canonical channel type 6 (TRPC6), a non-selective cation channel that mediates Ca²⁺ influx, is expressed in the heart and implicated in pathological cardiac hypertrophy. However, the role of TRPC6 in regulating cardiac mitochondrial metabolism and contributing to development of HFpEF remains unclear. We examined whether TRPC6 deficiency prevents mitochondrial dysfunction and offers cardiac protection in a mouse model of HFpEF induced by high-fat diet (HFD) for 12 weeks combined with L-NAME administration during the final 8 weeks in TRPC6 knockout (KO) and wild-type (WT) control mice. Cardiac systolic and diastolic functions were assessed at baseline, 4 and 8 weeks after HFD+L-NAME. Dobutamine-induced stress test and treadmill exercise test were performed at the end of the protocol to evaluate cardiac reserve capacity and exercise tolerance. Mitochondrial oxygen consumption rate (OCR) and mitochondrial-derived reactive oxygen species (ROS) generation were examined in isolated cardiac fibers. WT mice subjected to HFD+L-NAME developed cardiac hypertrophy, diastolic dysfunction, and exercise intolerance, whereas TRPC6 KO mice, under the same conditions, maintained preserved diastolic function, exercise tolerance, and cardiac reserve. We also observed increased TRPC6 in mitochondria, as well as caspase-9 activation and impaired mitochondrial respiration in WT mice. In contrast, TRPC6 KO mice exhibited preserved mitochondrial OCR and attenuated mitochondrial ROS generation. In summary, TRPC6 deficiency prevents the development of HFpEF by mitigating diastolic dysfunction, preserving cardiac reserve capacity, and attenuating mitochondrial dysfunction. Full article

During pregnancy, physiological adaptations occur in the respiratory and cardiovascular systems to support the increased metabolic needs of both mother and fetus. Key respiratory changes include mechanical adjustments of the chest wall and diaphragm to accommodate the growing uterus; decreases in functional residual capacity and its components—expiratory reserve volume and residual volume—with minimal or no change in total lung capacity; and an increase in minute ventilation. Major cardiovascular adaptations involve elevated cardiac output, stroke volume and heart rate, and decreased mean arterial pressure and systemic vascular resistance. During exercise in pregnancy, there is an increase in ventilation, alveolar diffusion, elevated oxygen consumption, greater carbon dioxide production and changes in respiratory volumes and capacities, as well as increases in cardiac output, stroke volume and heart rate. Understanding these normal physiological changes during pregnancy and exercise in pregnancy is essential for healthcare providers to develop and adapt exercise programs according to the gestational age and physical fitness level of the pregnant woman. Full article

Background: Cardiopulmonary exercise testing (CPET) is increasingly recognized as a key tool for evaluating patients with congenital heart disease (CHD). While traditional assessments focus on resting parameters, CPET provides dynamic, integrated insight into cardiovascular, respiratory, and muscular function during exertion. Objectives: This review explores the clinical value of CPET across the spectrum of CHD, with dedicated focus on its applications in both adult and paediatric populations. We analyse the prognostic significance of key CPET parameters—particularly peak oxygen consumption (peak VO₂), ventilatory efficiency (VE/VCO₂ slope), and heart rate dynamics—within distinct anatomical and physiological categories of CHD. Findings: CPET reliably detects exercise intolerance, guides intervention timing, informs exercise prescription, and stratifies risk. Peak VO₂ and heart rate reserve are consistently associated with adverse outcomes across most CHD types. However, the prognostic utility of other variables, such as the VE/VCO₂ slope, varies with pathophysiology—being less reliable in cyanotic lesions like Eisenmenger syndrome. In paediatric patients, CPET must be adapted to growth-related physiological variability and is increasingly used to assess quality of life, functional limitation, and response to therapy. Conclusions: CPET is a powerful, non-invasive tool that should be integrated into routine management of CHD patients across all ages. It enhances risk assessment, supports tailored care, and promotes safe physical activity, ultimately contributing to improved long-term outcomes and quality of life. Full article