Predictors of cardiovascular implantable electronic device dependence at long-term follow-up after alcohol septal ablation in hypertrophic cardiomyopathy patients.

BACKGROUND: The most common complication of alcohol septal ablation (ASA) is transient periprocedural high-grade AV block (HGAVB). To date, no long-term follow-up of cardiovascular implantable electronic device (CIED) utilization after ASA has been reported. We hypothesized that CIED dependence on long-term follow-up can be predicted by ECG or procedural characteristics. METHODS: We analyzed all patients with HCM who underwent ASA from December 1998 to December 2019 and received their first CIED within 30 days after ASA for HGAVB. All follow-up interrogations were reviewed. CIED dependence was defined as ventricular pacing of ≥ 5%. RESULTS: A total of 138 patients with HCM underwent ASA. Of these, 35 had a prior device and were excluded. Of the remaining 103 patients, 25 patients received a CIED for HGAVB within 30 days after ASA. Average follow-up duration was 10.1 years. On long-term follow-up, 16 patients (64%) were found to be CIED-dependent. Baseline characteristics, including pre- and post-ASA ECG, were not significantly different between dependent and non-dependent patients. The only predictor for CIED dependence was > 1 ml of alcohol injected (OR 6.0, p = 0.031). CONCLUSIONS: CIED implantation after ASA is common. Almost two thirds of patients who received a CIED for post-procedural HGAVB were CIED-dependent on long-term follow-up. CIED dependence can be predicted by the amount of injected alcohol > 1 ml.

Cell type-specific roles of PAR1 in Coxsackievirus B3 infection.

Protease-activated receptor 1 (PAR1) is widely expressed in humans and mice, and is activated by a variety of proteases, including thrombin. Recently, we showed that PAR1 contributes to the innate immune response to viral infection. Mice with a global deficiency of PAR1 expressed lower levels of CXCL10 and had increased Coxsackievirus B3 (CVB3)-induced myocarditis compared with control mice. In this study, we determined the effect of cell type-specific deletion of PAR1 in cardiac myocytes (CMs) and cardiac fibroblasts (CFs) on CVB3-induced myocarditis. Mice lacking PAR1 in either CMs or CFs exhibited increased CVB3 genomes, inflammatory infiltrates, macrophages and inflammatory mediators in the heart and increased CVB3-induced myocarditis compared with wild-type controls. Interestingly, PAR1 enhanced poly I:C induction of CXCL10 in rat CFs but not in rat neonatal CMs. Importantly, activation of PAR1 reduced CVB3 replication in murine embryonic fibroblasts and murine embryonic cardiac myocytes. In addition, we showed that PAR1 reduced autophagy in murine embryonic fibroblasts and rat H9c2 cells, which may explain how PAR1 reduces CVB3 replication. These data suggest that PAR1 on CFs protects against CVB3-induced myocarditis by enhancing the anti-viral response whereas PAR1 on both CMs and fibroblasts inhibits viral replication.

The use of MitraClip to prevent posttranscatheter aortic valve replacement left ventricular "suicide".

Patients with concomitant severe aortic stenosis (AS) and left ventricular outflow tract (LVOT) obstruction undergoing transcatheter aortic valve replacement (TAVR) are at risk for hemodynamic collapse due to a sudden decrease in afterload causing worsening LVOT obstruction. We present a case of an 88-year-old female with symptomatic, severe AS, and LVOT obstruction with systolic anterior motion (SAM) of the mitral leaflet in whom alcohol septal ablation was contraindicated secondary to a chronic total occlusion of the right coronary artery that filled retrograde via septal collaterals. MitraClip at the time of TAVR was successfully performed to treat SAM with subsequent stabilization of LVOT gradients despite treatment of the patient's AS. This novel approach may represent a feasible option to prevent hemodynamic complications after TAVR in patients with significant LVOT obstruction secondary to SAM and AS.

Correction to: Integrating basic science in academic cardiology training: two international perspectives on a common challenge.

Unfortunately, the + and - signs marking the benefits and challenges in Table 1 have been omitted during the typesetting of the article.

Integrating basic science in academic cardiology training: two international perspectives on a common challenge.

Political bodies and professional societies acknowledge that translational research benefits from researchers trained in both, clinical medicine and basic science. Yet, few physicians undergoing clinical training in cardiology seek this dual career (Milewicz et al. J Clin Invest 125:3742-3747, 2015). The reasons are likely manifold, but with cardiology having become increasingly interventional and facing economic pressure, how much attention, credit, and encouragement is given to physicians interested in basic cardiovascular science? Having studied and worked in hospitals and laboratories, in both Germany and the USA, we aim to compare in this article how basic science education is currently integrated into cardiology training at German and US university hospitals, from medical school to more advanced career stages. By doing so, we hope to provide some outside perspectives to young physicians and decision makers alike, that may inspire changes to curricula in the respective countries and around the world.

The factor Xa inhibitor rivaroxaban reduces cardiac dysfunction in a mouse model of myocardial infarction.

INTRODUCTION: Rivaroxaban selectively inhibits factor Xa (FXa), which plays a central role in blood coagulation. In addition, FXa activates protease-activated receptor-2 (PAR-2). We have shown that PAR-2-/- mice exhibit less cardiac dysfunction after cardiac injury. MATERIAL AND METHODS: Wild-type (WT) and PAR-2-/- mice were subjected to left anterior descending artery (LAD) ligation to induce cardiac injury and heart failure. Mice received either placebo or rivaroxaban chow either starting at the time of surgery or 3 days after surgery and continued up to 28 days. Cardiac function was measured by echocardiography pre-surgery and 3, 7 and 28 days after LAD ligation. We also measured anticoagulation, intravascular thrombi, infarct size, cardiac hypertrophy and inflammation at various times. RESULTS: Rivaroxaban increased the prothrombin time and inhibited the formation of intravascular thrombi in mice subjected to LAD ligation. WT mice receiving rivaroxaban immediately after surgery had similar infarct sizes at day 1 as controls but exhibited significantly less impairment of cardiac function at day 3 and beyond compared to the placebo group. Rivaroxaban also inhibited the expansion of the infarct at day 28. Rivaroxaban did not significantly affect the expression of inflammatory mediators or a neutrophil marker at day 2 after LAD ligation. Delaying the start of rivaroxaban administration until 3 days after surgery failed to preserve cardiac function. In addition, rivaroxaban did not reduce cardiac dysfunction in PAR-2-/- mice. CONCLUSIONS: Early administration of rivaroxaban preserves cardiac function in mice after LAD ligation.

A combined deficiency of tissue factor and PAR-4 is associated with fatal pulmonary hemorrhage in mice.

INTRODUCTION: Mice with a complete absence of tissue factor (TF) die during embryonic development whereas mice with low levels of TF (Low-TF mice) survive to adulthood. Low-TF mice exhibit spontaneous hemorrhage in various organs, including the lung. In contrast, mice can survive without protease-activated receptor (PAR)-4, which is the major thrombin receptor on mouse platelets. We determined the effect of combining a deficiency PAR-4 (primary hemostasis) with a deficiency in TF (secondary hemostasis) on embryonic development and survival of adult mice. MATERIALS AND METHODS: Low-TF mice (mTF-/-, hTF+/+) were crossed with PAR-4-/- mice to generate heterozygous mice (mTF+/-, hTF+/-, PAR-4+/-). These mice were intercrossed to generate Low-TF mice lacking PAR-4. Mice surviving to wean were genotyped and survival was monitored for 6months. RESULTS: We observed the expected number of Low-TF,PAR-4-/- mice at wean indicating survival in utero and after birth. However, an absence of PAR-4 was associated with premature death of all Low-TF,PAR-4-/- mice in the 6month observational period. This compares with 40% death of the Low-TF,PAR-4+/+ mice (p=0.003). Low-TF,PAR-4+/- mice had an intermediate phenotype with 55% of the mice dying within 6months. The primary cause of mortality of Low-TF,PAR-4-/- mice was pulmonary hemorrhage. CONCLUSIONS: Low-TF,PAR-4-/- mice survive into adulthood, but combining a deficiency of primary hemostasis (PAR-4 deficiency) with secondary hemostasis (low levels of TF) leads to premature death primarily due to pulmonary hemorrhage.

Prominent R wave in ECG lead V1 predicts improvement of left ventricular ejection fraction after cardiac resynchronization therapy in patients with or without left bundle branch block.

BACKGROUND: QRS morphology on postprocedural ECG indicating posterolateral left ventricular pacing may be predictive of response to cardiac resynchronization therapy (CRT). OBJECTIVE: The purpose of this study was to assess whether a positive vector in V1 and/or negative vector in lead I on the first postprocedural ECG, suggesting posterolateral capture from CRT, correlates with improvement in left ventricular ejection fraction (LVEF). METHODS: A retrospective chart review was conducted on all patients who underwent CRT implantation at our institution between April 2008 and December 2011. Biventricular (BiV) paced QRS morphology was defined as R/S ≥1 in V1 and/or R/S ≤ 1 in lead I. The primary outcome was improvement of LVEF ≥7.5%. The χ(2) and t tests were used for analysis. RESULTS: Of 68 patients, 49 (72%) met our BiV paced QRS morphology criteria. Thirty-four of these 49 patients (69%) had improvement in LVEF. Of the 19 patients who did not meet our criteria, 17 (89%) did not have an improvement in LVEF (sensitivity 94%, specificity 53%, χ(2) = 19.04, P < .0001). The average LVEF improvement in patients who met our BiV paced QRS morphology criteria was significantly greater than in those who did not (14.27% vs 2.63%, P = .0001). Preprocedural left bundle branch block was not a predictor of echocardiographic response. CONCLUSION: Our results highlight the importance of periprocedural ECG analysis to optimize response to CRT. Moreover, patients without left bundle branch block still benefited from CRT if they met our BiV paced morphology criteria. This suggests that postprocedural left ventricular activation as reflected on the ECG may supersede the baseline conduction delay.

Binary orbits as the driver of γ-ray emission and mass ejection in classical novae.

Classical novae are the most common astrophysical thermonuclear explosions, occurring on the surfaces of white dwarf stars accreting gas from companions in binary star systems. Novae typically expel about 10(-4) solar masses of material at velocities exceeding 1,000 kilometres per second. However, the mechanism of mass ejection in novae is poorly understood, and could be dominated by the impulsive flash of thermonuclear energy, prolonged optically thick winds or binary interaction with the nova envelope. Classical novae are now routinely detected at gigaelectronvolt γ-ray wavelengths, suggesting that relativistic particles are accelerated by strong shocks in the ejecta. Here we report high-resolution radio imaging of the γ-ray-emitting nova V959 Mon. We find that its ejecta were shaped by the motion of the binary system: some gas was expelled rapidly along the poles as a wind from the white dwarf, while denser material drifted out along the equatorial plane, propelled by orbital motion. At the interface between the equatorial and polar regions, we observe synchrotron emission indicative of shocks and relativistic particle acceleration, thereby pinpointing the location of γ-ray production. Binary shaping of the nova ejecta and associated internal shocks are expected to be widespread among novae, explaining why many novae are γ-ray emitters.