The prevalence of pacing-induced cardiomyopathy (PiCMP) has been reported to be 9% 1 year after implantation. As long-term data are sparse, the aim of our study was to evaluate the prevalence of PiCMP in a cohort of patients with at least 15 years of right ventricular (RV) pacing. Inclusion criteria were RV stimulation for at least 15 years due to atrioventricular block III° and absence of structural heart disease at the time of initial implantation. All patients were examined by echocardiography and spiroergometry. Pacing-induced cardiomyopathy was pre-defined as left ventricular (LV) ejection fraction (LVEF) ≤45%, dyskinesia during RV pacing and absence of other known causes of cardiomyopathy. Twenty-six patients from our outpatient department met the inclusion criteria. Pacing-induced cardiomyopathy was diagnosed in four patients (15.4%). Echocardiography showed significant LV remodelling in PiCMP patients [LVEF 41.0 ± 4.5%, LV end-diastolic diameter (LVEDD) 54.0 ± 2.7 mm] compared with patients with preserved LVEF (LVEF 61.2 ± 5.8%, P = 0.002, LVEDD 45.6 ± 4.0 mm, P= 0.004). There were no significant differences regarding age, gender, duration of RV pacing, heart rate, interventricular mechanical delay, QRS duration or prevalence of sinus rhythm, and arterial hypertension between both groups. The longest intraventricular delay was significantly shorter in patients with preserved LVEF (65.5 ± 43.0 ms) compared with PiCMP patients (112.5 ± 15.0 ms, P= 0.043). Exercise capacity and quality of life did not differ significantly between both groups. Considering the very long duration of RV stimulation in our study population (24.6 ± 6.6 years), the prevalence of PiCMP was remarkably low. Pacing-induced cardiomyopathy was associated with more pronounced intraventricular dyssynchrony.

Isovolumetric acceleration (IVA) is a novel tissue Doppler parameter for the assessment of systolic function. The aim of this study was to evaluate IVA as an early parameter for the detection of right ventricular (RV) systolic dysfunction in patients with systemic sclerosis (SSc) without pulmonary hypertension.

Rupture of the fibrous cap (RFC) and erosion of an intact fibrous cap (IFC) are the two predominant mechanisms causing acute coronary syndromes (ACS). It is uncertain whether clinical outcomes are different following RFC-ACS vs. IFC-ACS and whether this is affected by a specific inflammatory response. The prospective, translational OPTIcal-COherence Tomography in Acute Coronary Syndrome study programme investigates the impact of the culprit lesion phenotype on inflammatory profiles and prognosis in ACS patients. This analysis included 398 consecutive ACS patients, of which 62% had RFC-ACS and 25% had IFC-ACS. The primary endpoint was a composite of cardiac death, recurrent ACS, hospitalization for unstable angina, and target vessel revascularization at 2 years [major adverse cardiovascular events (MACE⁺)]. Inflammatory profiling was performed at baseline and after 90 days. Patients with IFC-ACS had lower rates of MACE⁺ than those with RFC-ACS (14.3% vs. 26.7%, P = 0.02). In 368-plex proteomic analyses, patients with IFC-ACS showed lower inflammatory proteome expression compared with those with RFC-ACS, including interleukin-6 and proteins associated with the response to interleukin-1β. Circulating plasma levels of interleukin-1β decreased from baseline to 3 months following IFC-ACS (P < 0.001) but remained stable following RFC-ACS (P = 0.25). Interleukin-6 levels decreased in patients with RFC-ACS free of MACE⁺ (P = 0.01) but persisted high in those with MACE⁺. This study demonstrates a distinct inflammatory response and a lower risk of MACE⁺ following IFC-ACS. These findings advance our understanding of inflammatory cascades associated with different mechanisms of plaque disruption and provide hypothesis generating data for personalized anti-inflammatory therapeutic allocation to ACS patients, a strategy that merits evaluation in future clinical trials. ACS, acute coronary syndrome; IFC, intact fibrous cap; IL-6, interleukin-6; LDLC, low-density lipoprotein cholesterol; MACE⁺, major adverse cardiovascular events, MΦ, macrophage; RFC, ruptured fibrous cap; TCFA, thin-cap fibro-atheroma. ns, not significant; *P < 0.05.

Participation of amateur runners in endurance races continues to increase. Previous studies of marathon runners have raised concerns about exercise-induced myocardial and renal dysfunction and damage. In our pooled analysis, we aimed to characterize changes of cardiac and renal function after marathon running in a large cohort of mostly elderly amateur marathon runners. A total of 167 participants of the BERLIN-MARATHON (female n = 89, male n = 78; age = 50.3 ± 11.4 years) were included and cardiac and renal function was analyzed prior to, immediately after and 2 weeks following the race by echocardiography and blood tests (including cardiac troponin T, NT-proBNP and cystatin C). Among the runners, 58% exhibited a significant increase in cardiac biomarkers after completion of the marathon. Overall, the changes in echocardiographic parameters for systolic or diastolic left and right ventricular function did not indicate relevant myocardial dysfunction. Notably, 30% of all participants showed >25% decrease in cystatin C-estimated glomerular filtration rate (GFR) from baseline directly after the marathon; in 8%, we observed a decline of more than 50%. All cardiac and renal parameters returned to baseline ranges within 2 weeks after the marathon. The increase in cardiac biomarkers after completing a marathon was not accompanied by relevant cardiac dysfunction as assessed by echocardiography. After the race, a high proportion of runners experienced a decrease in cystatin C-estimated GFR, which is suggestive of transient, exercise-related alteration of renal function. However, we did not observe persistent detrimental effects on renal function.

The histone methyltransferase enhancer of zeste homolog 2 (Ezh2) mediates trimethylation of lysine 27 in histone 3, which acts as a repressive epigenetic mark. Ezh2 is essential for maintaining pluripotency of stem cells, but information on its role in differentiated cells is sparse. Whole-genome mRNA expression arrays identified 964 genes that were regulated by >2-fold 72 hours after small interfering RNA-mediated silencing of Ezh2 in human umbilical vein endothelial cells. Among them, genes associated with the gene ontology terms cell communication and cell adhesion were significantly overrepresented, suggesting a functional role for Ezh2 in the regulation of angiogenesis. Indeed, adhesion, migration, and tube formation assays revealed significantly altered angiogenic properties of human umbilical vein endothelial cells after silencing of Ezh2. To identify direct target genes of Ezh2, we performed chromatin immunoprecipitation experiments followed by whole-genome promoter arrays (chromatin immunoprecipitation-on-chip) and identified 5585 genes associated with trimethylation of lysine 27 in histone 3. Comparative analysis with our mRNA expression data identified 276 genes that met our criteria for putative Ezh2 target genes, upregulation by >2-fold after Ezh2 silencing and association with trimethylation of lysine 27 in histone 3. Notably, we observed a striking overrepresentation of genes involved in wingless-type mouse mammary tumor virus integration site (WNT) signaling pathways. Epigenetic regulation of several of these genes by Ezh2 was specifically confirmed by polymerase chain reaction analysis of DNA enrichment after chromatin immunoprecipitation using an antibody specific for trimethylation of lysine 27 in histone 3. Combining mRNA expression arrays and chromatin immunoprecipitation-on-chip analysis, we identified 276 Ezh2 target genes in endothelial cells. Ezh2-dependent repression of genes involved in cell adhesion and communication contributes to the regulation of angiogenesis.

Transcatheter tricuspid valve replacement (TTVR) has been recently approved for the treatment of patients with severe tricuspid regurgitation (TR). Real-world evidence regarding the commercial use of TTVR is lacking. The aim of this study was to investigate the real-world safety and efficacy of the EVOQUE TTVR system in patients with severe TR treated at 12 experienced heart valve centers in 5 European countries. Consecutive patients treated with the EVOQUE system since approval in Europe (October 2023 to February 2025) were included in this retrospective analysis. Clinical outcomes were assessed at 30-day follow-up. The study included 176 patients (mean age 77.8 years, 72.0% women, median TRI-SCORE 5 points [IQR: 2 points]). At a median follow-up time of 30 days (IQR: 2 days), severe or greater TR was reduced to mild or none in 126 of 128 patients (98.4%; P < 0.001). NYHA functional class improved from 20.2% (28 of 138) class I or II at baseline to 79.7% (110 of 138; P) at 1 month (P < 0.001), with signs of improved hepatorenal function (estimated glomerular filtration rate 47.0 ± 19.9 mL/min/1.73 m² vs 53.7 ± 23.3 mL/min/1.73 m² [P < 0.001]; bilirubin 14.2 ± 8.8 μmol/L vs 11.0 ± 9.8 μmol/L [P < 0.001]). Massive or torrential TR at baseline was more common among patients who improved compared with those with stable or worsening NYHA functional class (75 of 98 [76.5%] vs 20 of 40 [50.0%]; P = 0.004). Permanent pacemaker implantation was required in 21 of 111 pacemaker-naive patients (18.9%), in particular those with conduction disturbances at baseline (OR: 4.53; 95% CI: 1.73-11.82; P = 0.002). Moderate or severe right ventricular dysfunction was an independent predictor of clinical failure at 1-month follow-up (OR: 3.60; 95% CI: 1.39-9.32, P = 0.008). TR elimination following TTVR in a real-world setting was associated with significant symptom and end-organ functional improvement. Patients with massive or torrential TR were more likely to experience functional improvement. Pre-existing conduction disturbances are associated with increased risk for pacemaker implantation, while baseline right ventricular dysfunction is a strong predictor of adverse clinical outcomes.