Search Results (554)

Background and Objectives: SGLT2 inhibitors are foundational in heart failure therapy, yet their impact on left ventricular (LV) remodeling immediately following acute coronary syndrome (ACS) remains less defined. This study evaluated the association between early SGLT2 inhibitor initiation and structural recovery in a real-world post-ACS cohort. Materials and Methods: We conducted a retrospective observational study including 238 revascularized ACS patients, stratified into an SGLT2 inhibitor group (n = 71) and a control group (n = 167). Changes in LV ejection fraction (LVEF) and indexed LV mass (LVMi) were assessed by echocardiography at baseline and follow-up (mean 286 days). Multivariable regression models were adjusted for baseline imbalances and tested for interactions with diabetes status. Results: A significant “confounding by indication” was observed; the SGLT2 group presented a high-risk phenotype with higher diabetes prevalence (56.3% vs. 25.7%, p < 0.001), lower baseline LVEF (38.3% vs. 43.3%), and greater hypertrophy. After adjustment, statistical independence was attenuated by baseline severity, yet the SGLT2 group achieved follow-up structural outcomes comparable to lower-risk controls. Interaction analysis indicated these trends were consistent regardless of diabetes status (p > 0.05). Conclusions: In this high-risk ACS population, early SGLT2 inhibitor therapy was associated with stabilization of cardiac structure. Despite a profound baseline disadvantage, the recovery trajectory effectively aligned with that of a lower-risk population, highlighting a clinically relevant pattern of structural stabilization consistent across metabolic subgroups. Full article

Background: There exists some inconsistent evidence on the relationship between altered cardiac morphology, its function, and frailty. Therefore, this study aimed to assess the associations among frailty, lean body mass, central arterial stiffness, and cardiac structure and geometry in older people with a normal ejection fraction. Methods: A total of 205 patients >65 years were enrolled into this ancillary analysis of the FRAPICA study and were assessed for frailty with the Fried phenotype scale. Left ventricular dimensions and geometry were assessed with two-dimensional echocardiography. Fat-free mass was measured using three-site skinfold method. Parametric and non-parametric statistics and analysis of covariance were used for statistical calculations. Results: Frail patients were older and women comprised the majority of the frail group. Frail men and women had comparable weight, height, fat-free mass, blood pressure, central blood pressure, and carotid–femoral pulse wave velocity to their non-frail counterparts. There was a linear correlation between the sum of frailty criteria and left ventricular end-diastolic diameter (Spearman R = −0.17; p < 0.05) and relative wall thickness (Spearman R = 0.23; p < 0.05). In the analysis of covariance, frailty and gender were independently associated with left ventricular mass (gender: β of −0.37 and 95% CI of −0.50–−0.24 at p < 0.001), the left ventricular mass index (gender: β of −0.23 and 95% CI of −0.37–−0.09 at p < 0.001), and relative wall thickness (frailty: β of −0.15 and 95% CI of −0.29–−0.01 at p < 0.05; gender: β of 0.23 and 95% CI of 0.09–0.36 at p < 0.01). Frailty was associated with a shift in heart remodeling toward concentric remodeling/hypertrophy. Conclusions: Frailty is independently associated with thickening of the left ventricular walls and a diminished left ventricular end-diastolic diameter, which are features of concentric remodeling or hypertrophy. This association appears to be more pronounced in women. Such adverse cardiac remodeling may represent another phenotypic feature linked to frailty according to the phenotype frailty criteria. Full article

Low QRS voltage relative to left ventricle (LV) thickness is one of the red flag characteristics in the diagnosis of cardiac amyloidosis, and it can be measured by specific indexes. Few studies have clearly defined the diagnostic threshold of voltage indexes for light chain amyloidosis cardiomyopathy (AL-CA) patients and other patients with LV hypertrophy. This case–control study analyzed electrocardiograms and echocardiograms of patients with AL-CA, hypertrophic cardiomyopathy (HCM), and hypertension left ventricular hypertrophy (HTN-LVH) seen at a single university center from 2008 to 2022. Low QRS voltage and three different precordial voltage indexes were evaluated. Diagnostic thresholds for rule-in and rule-out were calculated for AL-CA against each control group. A single voltage–mass ratio based on cross-sectional area (CSA) exhibited most accurate diagnostic accuracy, and the value of ≤1.72 aids the rule-in of AL-CA against other causes of left ventricular hypertrophy, providing a positive predictive value (PPV) of 86% versus HCM and 75% versus HTN-LVH. Full article

Background: Hemodynamic overload induces left ventricular remodeling and heart failure across various clinical presentations. While geometric remodeling is classically associated with increased vascular resistance in hypertension, distinct patterns emerge under the mechanical stress of aortic stenosis (AS). Concept: The “Stress Septal Sign” (Triple S) represents a marker of stress-mediated hemodynamic overload driven by diverse stimuli, ranging from mechanical stress in AS to emotional triggers in acute stress cardiomyopathy. Within this spectrum, Stressed Heart Morphology describes a specific phenotype characterized by a predominant and hyperdynamic LV septal base. Results: Chronic hemodynamic stress in severe AS results in prominent basal septal hypertrophy. This remodeling is characterized by distinct tissue energetics: hypermetabolic activity at the basal septum contrasted with reduced metabolic activity or hypokinesis in the apical regions. These findings on myocardial geometry, function, and energetics align with the adaptive phase of LV remodeling. Conclusions: The presence of adaptive myocardial basal tissue suggests an advanced remodeling stage that may require timely therapeutic intervention in severe AS. Therefore, identifying these specific tissue characteristics offers a unifying imaging paradigm (Triple S) for assessing cardiac stress, independent of the primary etiology. Full article

Left ventricular (LV) apical obliteration represents a convergent imaging phenotype arising from diverse cardiac conditions, including thrombotic, hypertrophic, infiltrative, congenital, and neoplastic diseases. These conditions, despite sharing overlapping morphological features, require profoundly different management strategies. In this context, an accurate characterization of the LV apex is a cornerstone point, and can be performed through various techniques. Advances in multimodality imaging have substantially improved diagnostic precision, allowing clinicians to differentiate true obliteration from mimicking conditions such as hypertrabeculation, apical hypertrophy, or subendocardial fibrosis. This review provides a comprehensive overview of the anatomical variability of the LV apex and its implications for imaging interpretation. We appraise the role of echocardiography, including contrast-enhanced and speckle-tracking studies—alongside cardiac magnetic resonance (CMR), computed tomography (CT), and selective nuclear imaging in the evaluation of apical pathology. For each principal cause of apical obliteration—LV thrombus, apical hypertrophic cardiomyopathy, left ventricular non-compaction, endomyocardial fibrosis, cardiac amyloidosis, and intracardiac tumors—we outline key diagnostic clues, imaging red flags, and distinguishing tissue characteristics. Special emphasis is given to the incremental value of CMR for tissue characterization, thrombus detection, and fibrosis mapping, as well as to the interpretative challenges posed by apical foreshortening, near-field artefacts, and suboptimal acoustic windows. A practical, stepwise imaging framework is proposed to guide clinicians through the differential diagnosis of apical obliteration using an integrated multimodality approach. Future directions include the incorporation of 4D flow, advanced mapping techniques, and artificial intelligence-powered analysis to refine apical phenotyping and identify early disease signatures. Recognizing the full spectrum of apical pathology and its imaging manifestations is essential to prevent misdiagnosis, enable timely therapeutic decisions, and improve risk stratification. Full article

Background/Objectives: Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder driven by mutations in the NF1 gene, whose pathogenesis centers on the loss of neurofibromin function and subsequent hyperactivation of the RAS/MAPK pathway. Notably, to the best of our knowledge and following a systematic literature search conducted by our research team, no cases of NF1 complicated by severe cardiac structural abnormalities that ultimately lead to cerebral infarction have been reported to date. Thus, it is of paramount importance to avoid missed diagnosis by performing comprehensive cardiac-related examinations in patients with NF1. Case Presentation: A 20-year-old male patient diagnosed with NF1 presented with right-sided limb weakness and was initially identified with cerebral infarction. To clarify the underlying etiology, a comprehensive clinical evaluation was performed, including cardiac imaging assessments (to characterize cardiac structural changes) and whole-exome sequencing (to identify the presence of procoagulant gene mutations). Comprehensive evaluation revealed a spectrum of cardiac structural abnormalities in the patient: aortic valve prolapse with severe regurgitation, non-infective vegetations on the aortic valve leaflets, mild-to-moderate mitral regurgitation, left ventricular hypertrophy and dilation, and left atrial dilation. Whole-exome sequencing detected exclusively a pathogenic variant in the NF1 gene, with no other pathogenic/likely pathogenic variants or thrombophilia-associated polymorphisms being found. Laboratory investigations ruled out infectious etiologies, supporting the notion that NF1-mediated cardiac structural and developmental anomalies are the primary driver of cardiac vegetation formation, given the absence of other identified contributing factors; embolization of one such vegetation ultimately led to both splenic and cerebral infarction. Conclusions: This case emphasizes the necessity of implementing early and proactive cardiac evaluations in patients with NF1. Additionally, for NF1 individuals—particularly those presenting with suggestive vascular or cardiac symptoms—a comprehensive multifactorial assessment of thrombotic risk is critical. Collectively, maintaining clinical vigilance for cardiac abnormalities in NF1 patients and avoiding diagnostic oversight is essential to reduce life-threatening risks. Full article

Background/Objectives: Numerous studies have documented cardioprotective effects of adiponectin in animal models of cardiometabolic disease (CMD). Adiponectin receptor agonist ALY688 has demonstrated functional significance against pressure overload-induced cardiac remodeling events in a mouse model of heart failure with reduced ejection fraction (HFrEF), potentially through modulation of the systemic metabolome. However, the specific metabolites and their pathophysiological contribution to cardioprotection in cardiac hypertrophy or heart failure remain unclear. This study aimed to characterize systemic metabolic alterations across five tissues in HFrEF and determine how ALY688 modifies these pathways to mediate cardioprotection in the transverse aortic constriction (TAC) model. Methods: Targeted metabolic profiling was performed on heart, liver, muscle, epididymal white adipose tissue (eWAT), and serum collected five weeks post-surgery from wild-type male C57BL/6 mice. Mice underwent either Sham or TAC-induced left ventricular pressure overload, with or without daily subcutaneous ALY688 administration. Metabolites were quantified using liquid chromatography–tandem mass spectrometry (LC–MS/MS) and statistically analyzed at the tissue level. Results: Consistent with pathological cardiac remodeling, the comprehensive metabolomic analysis revealed that TAC induced widespread disruption of systemic metabolic homeostasis. ALY688 treatment significantly modified several key metabolite classes, including triglycerides (TGs) and glycosylceramides (HexCer). Notably, ALY688 also altered multiple gut-derived metabolites, including trimethylamine N-oxide (TMAO), 5-aminovaleric acid (5-AVA), and glycodeoxycholic acid (GDCA), highlighting a potential gut–liver–heart axis mediating its cardioprotective effects. Conclusions: These findings demonstrate that ALY688 mitigates TAC-induced metabolic dysregulation across multiple tissues. The identified metabolic signatures suggest that ALY688 exerts cardioprotective effects, at least in part, through restoration of systemic metabolic homeostasis and engagement of a gut–liver–heart metabolic axis. These results provide mechanistic insight into adiponectin receptor agonism and support further exploration of ALY688 as a potential therapeutic strategy for HFrEF. Full article

Hypertrophic cardiomyopathy (HCM), the most common inherited cardiac disorder, is usually caused by pathogenic variants in sarcomeric genes and is inherited in an autosomal dominant manner. Around 5% of cases are caused by variants in non-sarcomeric genes, which may involve alternative modes of inheritance. This study presents the first reported case of HCM associated with digenic contribution of heterozygous variants in two non-sarcomeric genes: ALPK3 and TRIM63. The patient was incidentally diagnosed with non-obstructive HCM in childhood and developed extreme myocardial hypertrophy with moderate heart failure at the age of 18. Rapid progressive left ventricular dysfunction promptly resulted in death at the age of 26. Genetic testing with an extended HCM panel identified no sarcomeric variants but revealed two truncating variants in the ALPK3 and TRIM63 genes. Whole-genome sequencing excluded any other causes of the disease. Heterozygous ALPK3 variants are typically associated with late-onset HCM, whereas TRIM63 variants are only considered pathogenic in a recessive state. This case, therefore, suggests a synergistic contribution of both variants to the development of a severe phenotype. The potential mechanisms of interaction between the protein products of ALPK3 and TRIM63 within the M-band of the sarcomere are discussed. Full article

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article

Coarctation of the aorta is a localized narrowing of the aortic lumen. This pathology leads to hypertension in upper extremity vessels, left ventricular hypertrophy and to impaired perfusion of the abdominal cavity and lower extremities. Along with traditional diagnostic methods, mathematical modeling is used for risk assessment and the prediction of disease outcomes. However, when applying numerical models to describe hemodynamic parameters, the choice of turbulence model to describe swirling flow occurring in the aorta in this pathology must be justified. Thus, three turbulence models, namely k-ε, k-ω, and SST were analyzed for the description of swirling flows in the study of coarctation’s effect on hemodynamic parameters and analysis of the mechanisms leading to various cardiovascular diseases caused by altered hemodynamics. The results revealed significant differences in swirling flow patterns between the k-ε and k-ω models, while the k-ω and SST models showed consistent results over the cardiac cycle. In the peak systolic phase, average velocity rises to 1.07–1.98 m·s⁻¹ for the k-ε model, 0.82–2.12 m·s⁻¹ for the k-ω model, 1.22–2.12 m·s⁻¹ for the SST model and 0.8–2.12 m·s⁻¹ for laminar flow. WSS values increase rapidly to 11–22 Pa in k-ε, 25–50 Pa in k-ω and SST models of turbulence, and 30–55 Pa for laminar flow. Significant differences were also evident in the prediction of wall shear stress, with the k-ε model giving values more than twice as high as the k-ω and SST models. The data obtained confirm the necessity of careful model selection for accurate hemodynamic parameter estimation, especially in coarctation. The findings of this study can be used for further physics-informed neural network analysis of evaluation of treatment evaluations for congenital heart disease patients. Full article

Background: The aim of this study is to assess the safety of sodium channel blocker (SCB) therapy in patients with atrial fibrillation (AF). Methods: The REGUEIFA registry is a prospective, observational, multicenter registry from a Community Health Area in Spain that recruited patients with AF, whom it followed for 2 years. Results: From the 997 patients, 632 were assigned to a rhythm control strategy and analyzed. Patients exposed to SCBs demonstrated a risk ratio (RR) of 0.38 (95% CI: 0.18–0.79; p = 0.007) for worsening heart failure (HF), and 0.40 (95% CI: 0.21–0.78; p = 0.005) for the composite endpoint (death, ischemic stroke, or worsening HF), with no significant differences in all-cause mortality, cardiovascular (CV) mortality, ischemic stroke, or bleeding compared with patients not exposed to SCBs. In the subgroup of patients with structural heart disease, no differences were observed between those exposed and those not exposed to SCBs across all the clinical outcomes analyzed (all-cause mortality, CV mortality, ischemic stroke, bleeding and composite event). However, a lower event trend was observed across all these variables. The rate of sinus rhythm at 2 years follow-up was significantly higher in the SCB group (81.8% vs. 63.9%; p < 0.001). During Cox regression analysis for all-cause mortality, SCB exposure was not identified as an independent factor (HR: 0.82; 95% CI 0.17–3.87; p = 0.802). Age (HR: 1.10; 95% CI: 1.04–1.17; p < 0.001) and HF (HR: 4.23; 95% CI: 1.63–11.00; p = 0.003) were the only predictors of mortality. Conclusions: SCB therapy appears to be safe and effective, both in the overall cohort and in the patient subgroup with AF and structural heart disease. These agents may play a role in AF management in patients with revascularized coronary heart disease, left ventricular hypertrophy, and HF with preserved left ventricular ejection fraction. Full article

Background: ^99mTc pyrophosphate scintigraphy (^99mTc-PYP) is useful for diagnosing transthyretin amyloid cardiomyopathy (ATTR-CA). We examined the characteristics of ^99mTc-PYP-positive patients at our institution. Methods: A total of 76 patients who underwent ^99mTc-PYP from December 2020 and March 2022 were grouped into ^99mTc-PYP-positive (P) and -negative (N) groups and compared. Results: Nine of seventy-six patients were positive (11.8%), and all patients were diagnosed with ATTR-CA by myocardial biopsy or clinical findings. The heart-to-contralateral lung ratio in the P group was significantly higher (N Group: 1.15, P Group: 1.92, p < 0.001). In the P group, the left ventricular posterior wall thickness was significantly thickened (N Group; 12.5 mm, P Group; 15.5 mm, p = 0.003). Electrocardiogram showed left ventricular hypertrophy (LVH) was observed more frequently in the N group (N Group; 30 patients (44.8%) and the P Group; 1 patient (11.1%), p < 0.001). In addition, the QTc interval was significantly prolonged in the P group (N Group; 422 msec, P Group; 456 msec, p = 0.001). Conclusions: In patients who have significant LVH on echocardiogram but not on electrocardiogram, ^99mTc-PYP may be useful for diagnosing ATTR-CA. However, the present study is a single-center retrospective study with a small number of patients, and the results are exploratory and hypothesis-generating. Prospective studies with a larger number of subjects are needed. Full article

Neurodegenerative synucleinopathies—including Parkinson’s disease, multiple system atrophy, pure autonomic failure, and dementia with Lewy bodies—often feature cardiovascular autonomic dysfunction. Neurogenic orthostatic hypotension (nOH) is common and symptomatic, while neurogenic supine hypertension (nSH) is less frequent but may carry long-term cardiovascular risks. Lifestyle measures are first-line for managing nSH, yet persistent hypertension unresponsive to nonpharmacological strategies presents a treatment dilemma. Limited trial data and unclear guidelines make it difficult to determine when antihypertensive therapy is appropriate. Evidence from studies on hypertension-mediated organ damage (HMOD)—assessed through markers such as carotid intima-media thickness, pulse wave velocity, left ventricular hypertrophy, estimated glomerular filtration rate, and white matter hyperintensities—suggests that nSH, rather than the underlying neurodegenerative disorder, drives vascular, cardiac, renal, and cerebral injury. Therefore, treatment decisions should be individualized. While antihypertensive therapy may help prevent subclinical organ damage, clinicians must balance this benefit against the risk of worsening nOH and further compromising overall prognosis. Full article

Background: Aging elevates reactive oxygen species (ROS) and weakens antioxidant defenses, contributing to cardiac dysfunction. The objective of this study was to determine whether sustained activation of skeletal muscle (SkM) Nrf2 preserves cardiac function during aging and to explore the underlying mechanisms, focusing on myocardial antioxidant pathways. Methods: Tamoxifen-induced SkM-specific Keap1 knockout male mice (iMS-Keap1^flox/flox; SkM-Nrf2 overexpression) were divided into young wild-type (Y-WT), aged wild-type (A-WT), and aged knockout (A-KO) groups. Cardiac performance was evaluated by echocardiography and invasive hemodynamics. Myocardial proteomics identified differentially expressed proteins (DEPs) and enriched biological pathways. Results: Compared with Y-WT, A-WT mice showed impaired left ventricular function, including reduced ejection fraction, prolonged isovolumic relaxation time, blunted inotropic response to dobutamine, and elevated Tau index. These age-related deficits were partially reversed in A-KO mice. Proteomic analysis revealed 561 DEPs between A-WT and Y-WT, and 741 DEPs between A-KO and A-WT, enriched in calcium signaling, Nrf2-mediated oxidative stress response, oxidative phosphorylation, ROS detoxification, and cardiac-specific processes, such as hypertrophy, conduction, and dilated cardiomyopathy. Conclusions: Lifelong SkM-Nrf2 activation strengthens myocardial antioxidant capacity and alleviates age-related cardiac dysfunction. These data support an antioxidant crosstalk between skeletal muscle and the heart, highlighting a potential therapeutic target for aging-associated heart failure. Full article

Heart Failure with Preserved Ejection Fraction (HFpEF) is an increasingly prevalent clinical syndrome that poses a significant public health challenge due to its complex pathophysiology, diagnostic limitations, and lack of effective therapies. Central to its development are multifactorial and interrelated mechanisms, including left ventricular diastolic dysfunction, myocardial fibrosis, inflammation, endothelial dysfunction, and cardiomyocyte hypertrophy. In recent years, noncoding RNAs (ncRNAs)—particularly microRNAs (miRNAs) and long noncoding RNAs (LncRNAs)—have emerged as critical regulators of these cellular and molecular pathways. This review outlines the major pathophysiological mechanisms underlying HFpEF and highlights the noncoding RNAs most extensively studied in this context. Several ncRNAs have shown promise as biomarkers for the diagnosis and prognosis of HFpEF, owing to their tissue specificity, stability in circulation, and involvement in disease-relevant pathways. However, their integration into routine clinical practice remains limited. Importantly, the regulatory functions of ncRNAs in HFpEF pathophysiology also position them as potential therapeutic targets. Early experimental studies demonstrate encouraging results, suggesting that ncRNA-targeted interventions may support the development of personalized treatment strategies tailored to the diverse clinical phenotypes observed in HFpEF. Full article