Journal of Cardiovascular Development and Disease最新文献

Cardiovascular diseases (CVDs) remain the leading cause of mortality worldwide [...].

The limited capacity for cardiomyocyte proliferation in the adult human heart restricts its ability to recover from injury. Building on discoveries in regenerative model systems, such as zebrafish and neonatal mice, reactivation of a latent potential for cardiomyocyte proliferation is a strategy to promote therapeutic heart regeneration. Although cardiomyocyte proliferation remains modest even with the most effective mitogenic stimuli identified to date, evidence for a potential functional benefit in pre-clinical model systems has led to the initiation of several early-phase clinical programs. Here, we review insights from model organisms that inform the potential efficacy and limitations of therapeutic cardiomyocyte proliferation, systems to study human cardiomyocyte proliferation, and the natural history of cardiomyocyte proliferation in the human heart. We also examine the translational trajectory of selected discoveries, including therapeutic delivery modalities, and attendant safety concerns. Finally, we discuss critical challenges that will need to be addressed to enable successful clinical translation.

(1) Background: Prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR) impairs left ventricular (LV) recovery and is more common in women due to smaller aortic dimensions. Although the Perceval sutureless valve provides larger effective orifice areas, sex-specific PPM outcomes remain unclear. This study evaluated sex-related differences in PPM incidence, severity, and early impact after Perceval AVR. (2) Methods: We retrospectively analyzed 139 patients (68 males, 71 females) who underwent Perceval AVR between 2016 and 2020. PPM was defined per Valve Academic Research Consortium-3 (VARC-3) criteria using indexed effective orifice area (EOAi) and stratified by body-mass-index (BMI) (<30 vs. ≥30 kg/m²). Echocardiography assessed hemodynamic performance. (3) Results: PPM was markedly more frequent in women than men (74.6% vs. 22.1%, p < 0.001). Among non-obese patients, 47.9% of females versus 16.2% of males developed PPM (p < 0.001). Women received smaller valves and consistently exhibited lower EOAi despite similar gradients. Postoperatively, females had reduced EOAi (0.8 vs. 0.9 cm²/m², p < 0.001) but higher LV ejection fraction (55.8% vs. 49.5%, p = 0.004). Early clinical outcomes were comparable between sexes. (4) Conclusions: Despite favorable hemodynamics of sutureless AVR, anatomical sex differences result in persistently higher PPM rates in women, predominantly of moderate severity. Tailored strategies-including aortic root enlargement and sex-specific EOAi thresholds-may improve prosthesis selection and outcomes in female patients.

Durable left ventricular assist devices (LVADs) are an established and highly effective therapy for patients with advanced heart failure. Ongoing technological improvements and structured follow-up programs have significantly enhanced device durability, reduced complications, and improved long-term survival. Consequently, a growing number of patients with LVAD support require long-term outpatient care and increasingly present to both specialized and non-specialized hospitals, including for admissions unrelated to heart failure. In this context, echocardiography plays a central role. It is essential not only for routine follow-up at dedicated LVAD clinics but also for the assessment of cardiac status during inpatient admissions for extracardiac conditions. However, echocardiographic evaluation in LVAD patients is technically demanding and requires a solid understanding of LVAD physiology, device-heart interactions, and the specific hemodynamic conditions of continuous-flow support. Without this knowledge, standard echocardiographic parameters may be misleading. This review provides sonographers and cardiologists with a practical, clinically oriented framework for routine transthoracic echocardiography in patients with durable LVAD support. We summarize key principles of LVAD hemodynamics, discuss interpretation of LVAD console parameters, propose a standardized imaging protocol, and outline a structured approach to common echocardiographic findings in routine ambulatory and inpatient settings.

The severity of viral myocarditis in humans and mice is variable between individuals. Numerous observations demonstrate the influence of host genetics on disease course, but few genes have actually been identified to have such properties. In past work, mouse strains that are sensitive or resistant to severe disease were used to map the viral myocarditis susceptibility locus Vms1. Here, we demonstrate that Tnni3k, one of the genes within the Vms1 locus, influences the severity of disease following inoculation with coxsackievirus CVB3. Compared to disease-resistant C57BL/6J wild-type mice, strain-matched Tnni3k knockout mice showed higher cardiac inflammation and, in particular, a greater infiltration of macrophages into the heart. Long-term damage associated with viral infection was comparable in mice of both genotypes. Use of a second mouse line engineered with a point mutation to encode a kinase-dead version of Tnni3k showed the same elevated inflammation as the full null. These results identify Tnni3k and its kinase activity as being protective in modulating the acute phase of inflammatory response to CVB3 infection in the heart.

We greatly appreciate the thoughtful and detailed comments provided by Bruno Marino and his colleagues [...].

We read with great interest the recent and important paper by Othman et al [...].

Neonatal arrhythmias, though relatively uncommon, can range from benign self-limiting conditions to life-threatening disorders requiring intensive management. Data on their clinical spectrum, management, and outcomes remain limited. This study aimed to evaluate the types, frequency, clinical characteristics, treatment strategies, and prognosis of neonatal arrhythmias in a tertiary pediatric cardiac center. We retrospectively reviewed neonates diagnosed with arrhythmia within the first 28 days of life at Basaksehir Cam and Sakura City Hospital between 1 January 2021 and 1 May 2025. Demographic data, electrocardiographic and echocardiographic findings, treatment modalities, recurrence, morbidity, and mortality were analyzed. Patients were categorized as having benign or non-benign arrhythmias. A total of 65 neonates (57% male, mean weight 3.2 kg) were included. Non-benign arrhythmias were more frequent (77%) compared to benign arrhythmias (23%). Supraventricular tachycardia (35%) was the most common non-benign arrhythmia, followed by long QT syndrome (10.7%) and complete atrioventricular block (9.2%). Antiarrhythmic therapy was required in 55% of patients. Pacemaker implantation was performed in seven infants with conduction disorders. Recurrence occurred in 3% of cases, exclusively among patients with supraventricular tachycardia. During a median follow-up of 12.8 months, no mortality was observed. Prenatal diagnosis and early management contribute to favorable outcomes, as reflected in the absence of mortality in this cohort. Larger, prospective studies are warranted to define optimal management strategies and treatment durations for neonatal arrhythmias.

Background: Endothelial dysfunction is a key player in stroke pathophysiology. The Endothelial Activation and Stress Index (EASIX) is a biomarker of endothelial injury validated in hematology, sepsis, and cardiovascular cohorts; however, its prognostic role in stroke remains unclear. This retrospective cohort study aims to provide preliminary evidence on the potential utility of EASIX levels as a biomarker for assessing stroke severity and predicting outcomes.

Methods: We retrospectively studied 100 patients aged ≥ 18 years admitted with acute ischemic stroke (AIS) or transient ischemic attack (TIA) between January 2020 and July 2024. EASIX was calculated on admission as LDH × creatinine/platelets. Outcomes included in-hospital and 12-month mortality, stroke severity assessed by the NIHSS score, and disability assessed as a modified Rankin score (mRS).

Results: Median age was 82 years; 56% were female. The in-hospital and 12-month mortality rates were 47.9% in patients with AIS and 17.2% in patients with TIA, respectively. Overall, EASIX was not associated with NIHSS, mRS, or mortality in the total cohort. Ιn the subgroup of patients with small vessel disease (n = 10), higher EASIX was associated with worse mRS at 12 months (β = 2.383, p = 0.02) and increased mortality (β = 0.653, p = 0.02). EASIX correlated positively with WBC (p < 0.001) and CRP (p = 0.01). Female sex was associated with lower EASIX values.

Conclusions: EASIX was not associated with outcomes in the overall AIS/TIA cohort, but it demonstrated potential prognostic relevance in small vessel disease (SVD), which has not been reported previously in the literature. Further prospective research is warranted to validate the potential association between systemic endothelial stress and small vessel disease before the implementation of EASIX as a prognostic tool in patients with stroke due to SVD.

Background: Neurodegeneration and dementia are key factors in Alzheimer's disease (AD). The deposition of amyloid-ß into senile plaques in the brain parenchyma and in cerebral vessels known as cerebral amyloid angiopathy (CAA) are the main clinical parameters of AD. Acute myocardial infarction (AMI) and AD share a comparable pathophysiology. However, the underlying mechanisms and the consequences of AMI in AD patients are unclear to date.

Methods: AD transgenic APP23 mice were analyzed in experimental AMI using the closed-chest model.

Results: APP23 mice displayed significantly decreased left ventricular function as detected by FS/MPI (fractional shortening/myocardial performance index) after 24 h and 3 weeks after ligation of the LAD compared to WT controls. No differences have been observed in infarct and scar size. The analysis of cardiac remodeling after 3 weeks showed an altered composition of the collagen tissue of the scar with elevated tight but reduced fine collagen in APP23 mice. Altered scar formation was accompanied by elevated degranulation of platelets following activation of the collagen receptor GPVI.

Conclusions: These results suggest that AD patients are at higher risk for cardiac damage after AMI. This implies the need for a personalized therapy of AMI in AD patients.