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Infections related to cardiac implantable electronic devices (CIED) are associated with significant morbidity and mortality. Antibiotic-eluting envelopes have been introduced as a technology to prevent CIED infections. The aim of this study was to evaluate the effectiveness of the antibacterial envelope in the real-world population of a tertiary center. This cohort study includes consecutively enrolled patients undergoing a device procedure from 01/2014 to 12/2020 at the University Hospital in Zurich. During period A (01/2014-12/2019) antibacterial envelopes were not used, whereas during period B (01/2020-12/2020) antibacterial envelopes were used in all device interventions. Follow-up was conducted by assessing all available patient records from patient visits and hospitalization. 1757 patients (male 70.5%, mean age 67.1 ± 16 years), were analyzed during a follow-up of 24 months. In 302 patients (17.2%) an antibacterial envelope was used. The overall occurrence of a device infection was low (n = 15, 0.85%). Factors that were associated with the incidence of an infection were not undergoing a primary implantation procedure (p = 0.024) and a CRT-P/D intervention (p = 0.022). There was no difference in the rate of infection between patients in whom a bacterial envelope was implanted vs. those in whom it was not used (0.6 vs. 0.9%, p = 0.693). In a contemporary cohort of consecutive, unselected patients undergoing a device intervention at a large tertiary care center, the rate of device infection was low and not significantly different with vs. without the use of an antibacterial envelope. The data have important practical as well as economic implications for physicians performing such procedures.

Purpose: Transcatheter heart valve replacements (TVR) are typically designed in a closed shape with initial leaflet coaptation. However, recent studies suggest a semi-closed geometry without a predefined coaptation zone, relying on diastolic pressure and clinical oversizing of 10–20 % for closure. This approach may minimize pinwheeling, a phenomenon linked to early valve degeneration. Method: Seven valve geometries were assessed: one closed design (G0) and six semi-closed variations (G1–G6). The semi-closed designs differed in free edge shape (linear, concave, convex) and opening degree, defined as the relative distance from the leaflet to the valve center in the unloaded state. The opening degree was systematically increased across G1–G6, with G6 exhibiting the highest value. 30 mm valves were fabricated using porcine pericardium and self-expanding nitinol stents. Performance was assessed in a pulse duplicator system, evaluating transvalvular pressure gradient (TPG), effective orifice area (EOA), regurgitation fraction (RF) and a novel pinwheeling index (PI) which was validated by finite element simulations. Results: Finite element simulations demonstrated that semi-closed geometries achieve valve closure at a diameter reduction of >5%. In vitro tests confirmed these findings with more homogeneous coaptation and reduced pinwheeling. With increased opening degree the RF reduced significantly (RFG0 = 18.54 ± 8.05%; RFG6 = 8.22 ± 1.27%; p < 0.0001), while valve opening remained comparable (p = 0.4519). Conclusions: A semi-closed leaflet geometry enhances valve closure, reducing regurgitation and pinwheeling while preserving effective opening. With clinical oversizing, a higher opening degree improves coaptation and may enhance durability by mitigating structural deterioration, ultimately improving the long-term performance and lifespan of transcatheter valve replacements.

Inflammation plays a key role in atherosclerosis. Sirt1 regulates transcription factors involved in inflammatory processes and blunts atherosclerosis in mice. However, its role in humans remains to be defined. This study was therefore designed to investigate the role of Sirt1 in the development of atherosclerosis. 48 male subjects admitted for cardiac catheterization were subdivided into healthy subjects, patients with stable coronary artery disease (CAD), and with acute coronary syndromes (ACS). Monocytes were isolated and Sirt1 mRNA levels were determined. Sirt1 gene expression was higher in healthy subjects as compared to patients with CAD or ACS (P<0.05), respectively. Interestingly, HDL levels correlated positively with Sirt1 expression. Thus, HDL from the three groups was isolated and incubated with THP-1 monocytes to determine the effects of HDL on Sirt1 protein in controlled experimental conditions. HDL from healthy subjects stimulated Sirt1 expression in THP-1 monocytes to a higher degree than HDL from CAD and ACS patients (P<0.05). Paraoxonase-1 (PON-1), a HDL-associated enzyme, showed a reduced activity in HDL isolated from CAD and ACS patients as compared to the controls (P<0.001). Monocytic Sirt1 expression is reduced in patients with stable CAD and ACS. Experiments on THP-1 monocytes suggest that this effect is HDL-dependent and is mediated by a reduced activity of HDL-associated enzyme PON1.

Left atrial (LA) fibrosis in patients with atrial fibrillation (AF) is associated with an increased risk of AF recurrence after catheter ablation. Therefore, we searched for clinical risk factors that confer an increased risk of LA fibrosis, which can influence the treatment strategy. We included 94 patients undergoing 3-dimensional electroanatomical voltage mapping-guided catheter ablation of AF. LA low-voltage areas during sinus rhythm as a surrogate parameter of fibrosis were measured with the CARTO3 mapping system and adjusted for LA volumes obtained by computed tomography. Blood tests including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and echocardiographic parameters of left ventricular function were also analyzed. Patients were 62.5 ± 11.4 years old, and 29% were female. LA fibrosis was present in 65%, with 50% having a fibrotic area > 5% (≥ Utah-Stage 1). Mean left ventricular ejection fraction (LVEF) was 53.9 ± 10.5%. Patients with LA fibrosis had higher NT-proBNP levels (869 ± 1056 vs. 552 ± 859 ng/L, p = 0.001) and larger LA volumes (body surface area-corrected 63.3 ± 19.3 vs. 80 ± 27.1 mL/m2, p = 0.003). In univariable analyses, LA fibrosis was significantly associated with female gender, older age, increased LA volumes, hypertension, statin therapy, higher NT-proBNP values, and echocardiographic E/e'. In bivariable analyses, higher NT-proBNP, echocardiographic parameters of diastolic dysfunction, female gender, older age, and higher DR-FLASH scores remained as independent predictors of LA fibrosis. In this single-center longitudinal study, surrogate parameters of elevated left-sided cardiac filling pressures such as higher NT-proBNP levels and higher echocardiographic E/e' values as well as female gender independently predicted the prevalence of LA fibrosis in patients referred for catheter ablation of AF.

Background Cardiac resynchronization therapy (CRT) is a key intervention for patients with heart failure. The choice between a CRT with defibrillator therapy (CRT‐D) and a CRT with pacemaker (CRT‐P) is influenced by individual clinical characteristics. This study explores the interaction between these clinical variables and the benefit of CRT‐D versus CRT‐P on all‐cause mortality. Methods All patients who underwent CRT implantation in three European centres were included in a multicentre, retrospective registry. The impact of clinical variables on all‐cause mortality was analysed using interaction tests within multivariable Cox proportional hazard models. Significant interactions were explored to assess how patient characteristics modify the effect of CRT‐D compared with CRT‐P. Results A total of 2271 patients with CRT implantation were included. CRT‐D was associated with a 35% reduction in all‐cause mortality compared with CRT‐P [hazard ratio (HR) 0.65; 95% confidence interval (CI) 0.53–0.80]. Significant interactions were observed for left bundle branch block (LBBB) morphology (P = 0.028), left ventricular ejection fraction (LVEF, P = 0.025) and renal function (P = 0.019). The survival benefit of CRT‐D was pronounced in patients with LBBB (HR 0.57; 95% CI 0.44–0.73) but was not significant in those without LBBB (HR 0.81; 95% CI 0.59–1.10). For LVEF at implant, CRT‐D provided benefit between 17.9% and 37.6%. Similarly, CRT‐D improved outcomes in patients with an estimated glomerular filtration rate >31.8 mL/min but not in those with more advanced renal impairment. No interaction was observed with age at implant (P = 0.286). Conclusions This study provides insights into the benefits of CRT‐D over CRT‐P, identifying LBBB morphology, LVEF and renal function as key covariates associated with implantable cardioverter–defibrillator (ICD) therapy's benefit.

His bundle (HB) potentials vary in amplitude and duration in patients with and without slow pathways. The aim of this study was to determine the characteristics of HB potentials and to elucidate whether they can provide clues for identification of slow pathway (SP). The present research prospectively studied the electrophysiological findings of 162 patients with symptomatic atrioventricular nodal reentrant tachycardia (AVNRT) due to slow-fast or fast-slow type and atrioventricular reentrant tachycardia (AVRT). Maximal HB potential (HBmax, HB with the highest amplitude) among HB cloud was recorded in both groups. For AVNRT patients, the following were measured: (1) AH interval at the \"jump\" during programmed atrial stimulation (A2H2, taken as a reflection of SP conduction time); (2) Distance from HBmax to the successful SP ablation site (HBmax-ABL) and from HBmax to the ostium of coronary sinus (HBmax-CSO). HBmax was 0.29 ± 0.10 mV in AVNRT patients, whereas it was 0.17 ± 0.05 mV in AVRT group (p < 0.0001). Likewise, the HBmax duration was 22 ± 5 ms in AVNRT group and 16 ± 3 ms in AVRT group (p < 0.0001). The area under the receiver operating characteristic curve of HBmax amplitude in AVNRT patients was 0.86 and the optimal HBmax cut-off to predict AVNRT was ≥ 0.22 mV with a sensitivity of 0.78 and specificity of 0.84. HBmax-CSO was positively correlated with HBmax-ABL, and HBmax-ABL was positively correlated with A2H2. HBmax amplitudes were higher and durations longer in patients with AVNRT, as compared to those with AVRT. Moreover, the distance between HBmax and successful ablation site was positively correlated with the SP conduction time and with the distance from HBmax to the CSO.

Background: Antiproliferative strategies have emerged as a potential therapeutic option for pulmonary arterial hypertension (PAH). Objective: To evaluate the long-term efficacy and safety of imatinib. Methods: This is an observational study of 15 patients with idiopathic PAH (n = 13) or PAH associated with connective tissue disease (n = 2) treated off-label with imatinib 400 mg daily. Pulmonary hypertension-specific therapy was established in all patients (triple therapy in 10, dual therapy in 3, and monotherapy in 2 patients). Results: After 6 months, improvement in hemodynamics (p < 0.01), functional class (p = 0.035), and quality of life (p = 0.005) was observed. After a median follow-up of 37 months, there was a sustained improvement in functional class (p = 0.032), quality of life (p = 0.019), and echocardiographic parameters of right ventricular function (p < 0.05). Three patients (20%) presented with completely normal echocardiography, absent tricuspid regurgitation, and normal pro-brain natriuretic peptide levels, indicative of ‘hemodynamic remission'. Of note, however, only 1 case was assessed by invasive hemodynamics. The overall 1- and 3-year survival was 100 and 90%, respectively. Two patients experienced a subdural hematoma (SDH), which in both cases resolved without sequelae. After careful consultation of the potential risks and benefits, all patients as well as a safety cohort of 9 subsequent cases decided to continue the imatinib therapy. After adjusting the target international normalized ratio (INR) to around 2.0, no further cases of SDH occurred during 50 patient-years. Conclusions: Long-term treatment with imatinib may improve the functional class and quality of life. Single cases might even attain hemodynamic remission. The occurrence of 5% SDH per patient-years is concerning. However, adjusting the INR to around 2.0 might obviate this complication.

Introduction: Hypertrophic cardiomyopathy (HCM) patients with left ventricular (LV) mid-cavity obstruction (LVMCO) often experience severe drug-refractory symptoms thought to be related to intraventricular obstruction. We tested whether ventricular pacing, guided by invasive haemodynamic assessment, reduced LVMCO and improved refractory symptoms. Methods: Between December 2008 and December 2017, 16 HCM patients with severe refractory symptoms and LVMCO underwent device implantation with haemodynamic pacing study to assess the effect on invasively defined LVMCO gradients. The effect on the gradient of atrioventricular (AV) synchronous pacing from sites including right ventricular (RV) apex and middle cardiac vein (MCV) was retrospectively assessed. Results: Invasive haemodynamic data were available in 14 of 16 patients. Mean pre-treatment intracavitary gradient was 77 ± 22 mmHg (in sinus rhythm) versus 21 ± 21 mmHg during pacing from optimal ventricular site (95% CI: −70.86 to −40.57, p < 0.0001). Optimal pacing site was distal MCV in 12/16 (86%), RV apex in 1/16 and via epicardial LV lead in 1/16. Pre-pacing Doppler-derived gradients were significantly higher than at follow-up (47 ± 15 versus 24 ± 16 mmHg, 95% CI: −37.19 to −13.73, p < 0.001). Median baseline NYHA class was 3, which had improved by ⩾1 NYHA class in 13 of 16 patients at 1-year post-procedure (p < 0.001). The mean follow-up duration was 4.6 ± 2.7 years with the following outcomes: 8/16 (50%) had continued symptomatic improvement, 4/16 had symptomatic decline and 4/16 died. Contributors to symptomatic decline included chronic atrial fibrillation (AF) (n = 5), phrenic nerve stimulation (n = 3) and ventricular ectopy (n = 1). Conclusion: In drug-refractory symptomatic LVMCO, distal ventricular pacing can reduce intracavitary obstruction and may provide long-term symptomatic relief in patients with limited treatment options. A haemodynamic pacing study is an effective strategy for identifying optimal pacing site and configuration.

Pulmonary veno-occlusive disease (PVOD) is a rare condition of pulmonary arterial hypertension (PAH), in which post-capillary veins are affected. Since the therapeutic approach in PVOD differs from other forms of PAH, it is crucial to establish the diagnosis. Due to the fact that affected patients are often hemodynamically unstable, minimal invasive procedures are necessary for the diagnostic work-up. Chronic alveolar haemorrhage has been observed during bronchoalveolar lavage in PVOD cases. This study therefore investigates whether signs of alveolar haemorrhage can also be found in the sputum of these patients. Six patients suffering from PVOD were included in this analysis. As controls, patients with idiopathic PAH (n = 11), chronic thromboembolic PH (n = 9) and with sclerodermia-associated PH (n = 10) were assessed. Sputum from every patient was obtained by a non-invasive manner. The amount of haemosiderin-laden macrophages was determined using the Golde score. There were statistically significant more haemosiderin-laden macrophages in the sputum of patients suffering from PVOD as compared to the other groups (P<0.05). Assuming a cut-off of 200 on the Golde score, all of the 6 PVOD patients surpassed this value compared with only 1 out of the 30 cases with precapillary PH. Thus, sensitivity and specificity with respect to the diagnosis of PVOD was 100% and 97%, respectively. The content of haemosiderin-laden macrophages in the sputum of patients suffering from PVOD is significantly higher as compared to other forms of PH and may be useful in the non-invasive diagnostic work-up of these patients.