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Sequential synchronized atrioventricular (AV) pacing provides enhanced electrophysiologic parameters which contribute to improved hemodynamic parameters and increased cardiac performance to subsequently confer a clinical advantage over traditional ventricular pacing. Current temporary transvenous pacemaker catheters are limited to only one electrode which paces solely the right ventricle, thus lacking the capability to provide the optimal pacing mode. A new multilead pacemaker device was developed in response to the need for improved temporary pacing through the utilization of sequential synchronized atrioventricular pacing (TAVSP). It consists of seven preformed, preshaped nitinol wires electrodes, of which four are for intra-atrial and three for intraventricular positioning and endocardial contact, respectively. Each wire carries a ball tip designed to minimize tissue trauma and provide a high current density for adequate myocardial capture. The device is not yet Food and Drug Administration approved.To present the unique structural components and mechanical properties of a novel sequential synchronized AV pacing device for temporary insertion and to report its first-in-human application with an analysis of the early clinical experience.Following a process of development and proof of concept of the novel pacing modality in an animal model which demonstrated feasibility and safety, a series of patients who were candidates for the device application was identified. During left and right heart catheterization, the novel temporary pacing catheter was inserted transvenously and delivered in most patients under fluoroscopy or echocardiography. The catheter was deployed to its target right heart anatomic sites and then activated in an AV sequential mode. The technical aspects, the corresponding clinical utilization, and device performance were documented and analyzed.The series included 10 enrolled subjects. During planned left and right heart catheterization, the novel TAVSP device was inserted transvenously and then delivered and deployed successfully in a timely fashion in all patients. The pacing catheter achieved proper threshold and impedance in all (100%) patients. The performance of all ventricular leads was adequate; however, in 1 (10%) patient poor performance of the atrial leads was detected. The device was successfully retrieved in all patients. No adverse arrhythmia, impaired hemodynamics, or clinical adverse events occurred. No technical difficulties, component failure, or wires thrombosis were detected. All patients sustained the device application without sequala and were discharged home.Initial clinical experience with the utilization of a novel TAVSP demonstrates feasibility and safety in humans. The TAVSP modality potentially offers improved pacing capability and subsequent hemodynamic benefits over the current temporary pacing catheters. Further experience with the clinical application of this pacing catheter is warranted.

Supplemental Digital Content is available in the text., Background: Cardiac involvement among hospitalized patients with severe coronavirus disease 2019 (COVID-19) is common and associated with adverse outcomes. This study aimed to determine the prevalence and clinical implications of COVID-19 cardiac involvement in young competitive athletes. Methods: In this prospective, multicenter, observational cohort study with data from 42 colleges and universities, we assessed the prevalence, clinical characteristics, and outcomes of COVID-19 cardiac involvement among collegiate athletes in the United States. Data were collected from September 1, 2020, to December 31, 2020. The primary outcome was the prevalence of definite, probable, or possible COVID-19 cardiac involvement based on imaging definitions adapted from the Updated Lake Louise Imaging Criteria. Secondary outcomes included the diagnostic yield of cardiac testing, predictors for cardiac involvement, and adverse cardiovascular events or hospitalizations. Results: Among 19 378 athletes tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, 3018 (mean age, 20 years [SD, 1 year]; 32% female) tested positive and underwent cardiac evaluation. A total of 2820 athletes underwent at least 1 element of cardiac triad testing (12-lead ECG, troponin, transthoracic echocardiography) followed by cardiac magnetic resonance imaging (CMR) if clinically indicated. In contrast, primary screening CMR was performed in 198 athletes. Abnormal findings suggestive of SARS-CoV-2 cardiac involvement were detected by ECG (21 of 2999 [0.7%]), cardiac troponin (24 of 2719 [0.9%]), and transthoracic echocardiography (24 of 2556 [0.9%]). Definite, probable, or possible SARS-CoV-2 cardiac involvement was identified in 21 of 3018 (0.7%) athletes, including 15 of 2820 (0.5%) who underwent clinically indicated CMR (n=119) and 6 of 198 (3.0%) who underwent primary screening CMR. Accordingly, the diagnostic yield of CMR for SARS-CoV-2 cardiac involvement was 4.2 times higher for a clinically indicated CMR (15 of 119 [12.6%]) versus a primary screening CMR (6 of 198 [3.0%]). After adjustment for race and sex, predictors of SARS-CoV-2 cardiac involvement included cardiopulmonary symptoms (odds ratio, 3.1 [95% CI, 1.2, 7.7]) or at least 1 abnormal triad test result (odds ratio, 37.4 [95% CI, 13.3, 105.3]). Five (0.2%) athletes required hospitalization for noncardiac complications of COVID-19. During clinical surveillance (median follow-up, 113 days [interquartile range=90 146]), there was 1 (0.03%) adverse cardiac event, likely unrelated to SARS-CoV-2 infection. Conclusions: SARS-CoV-2 infection among young competitive athletes is associated with a low prevalence of cardiac involvement and a low risk of clinical events in short-term follow-up.

Background. Current temporary transvenous pacemaker catheters lack sequential atrioventricular (AV) pacing in synchrony. Therefore, a catheter that could provide sequential AV pacing and maintain synchrony may be useful for patients in sinus rhythm who need temporary pacing. Objective. The purpose of this study was to describe the first in human experience with a novel temporary AV sequential pacing catheter (TAVSP). Methods. We prospectively identified eligible patients undergoing elective cardiac catheterization in whom the TAVSP catheter was delivered and used for temporary AV sequential pacing. Safety endpoints and device performance data were obtained. Results. Ten subjects were screened and enrolled in the study. TAVSP was delivered in all ten subjects, and AV sequential synchronous pacing was successfully obtained. The pacing catheter achieved an excellent pacing threshold and impedance in all ten patients except for one. There were no adverse events during the pacing procedure. Conclusion. Temporary AV sequential pacing using TAVSP catheter is safe and feasible and may be an alternative to conventional temporary pacing catheters to maintain AV synchrony during temporary pacing.

Background: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial. Methods: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n = 8), negative for any variants (V−; n = 6), or as variants of uncertain significance (VUS; n = 20). All outcomes of therapy were analysed for each category of genetic results. Findings: The 3 groups were indistinguishable at baseline with regard to ejection fraction (EF), demographics, medication use, or functional parameters. V− patients had an increase in EF at 12 months: +13.6% (IQR = +7.8%; +20.5%; p = 0.002), compared with VUS (+6.5%; IQR = +0.9%, +11.1%; p = 0.005) and PV+(−5.9%; IQR = −12.7%, +1.0; p = 0.2; p = 0.01 between groups). Six-minute walk distance improved in V- patients, but not in VUS and PV+. V− patients improved MLHFQ, compared to the other 2 groups, which did not improve over time. EPCCFUs increased by 9.7 ± 1.9 in V− (p = 0.009) compared to VUS and PV+ patients. V− patients had one-year survival (100%) compared with VUS (85%) and PV+ (40%; p = 0.015 log-rank). Similarly, MACE rates were lower in V− (0%) than PV+ (61.9%) or VUS (42.2%; p = 0.021 log-rank). Interpretation: Our findings support the concept that the genetic profile of NIDCM patients plays a role in responsiveness to MSC therapy, with V− patients more likely to benefit and the converse for PV+. This observation emphasizes the need for further genetic studies, because of important implications for the management of NIDCM syndromes. Keywords: Precision medicine, Variants of uncertain significance, Positive for pathologic/likely pathologic variant, Dilated cardiomyopathy

Background: While pulmonary vein isolation (PVI) for treatment of persistent atrial fibrillation (PeAF) is successful in approximately 50%, acute termination of PeAF is rarely observed. Prolongation of cycle length (CL) by 10% is often utilized as an indicator of successful catheter ablation (CA). Objective: To evaluate coronary sinus (CS) cycle length (CL) before and after CA for PeAF. Methods: CA for PeAF was performed in 31 patients (24males, age 63±9 yrs, CHA2DS2-VASc 2.3±1.7, LVEF 49±10%) with PVI, with 4 (13%) also having posterior wall isolation. A multielectrode catheter was placed in the CS and maintained throughout the procedure. CS electrograms were recorded for 10 seconds prior to CA and after completion of CA. No patient reverted to sinus rhythm during CA. CS CL was determined using customized software for activation detection and verified visually, excluding ventricular activation and low quality signals (n=3). The shortest CL among the recording electrodes was used for analysis. Results: CS CL pre- and post-CA were 182.4±23.0 and 191.6± 29.9 ms (p= 0.04) with change from baseline of 5.4±12.7%. The figure shows the histogram for change in CS CL from baseline. Only 7/28 (25%) of patients had CS CL prolongation >10%. Of ten patients who were free of AF off anti-arrhythmic drugs at 1 year, CS CL increased 4.0±6.1%; 2/10 had CS CL prolongation >10%. Of 6 patients with recurrent AF, CS CL increased 13.8±20.7%; 4/6 had CS CL prolongation >10%. Conclusion: Our data demonstrate that CS CL prolongation >10% is not a useful marker of outcomes in patients undergoing catheter ablation for PeAF. This highlights the need to identify other indicators of acute ablation success.

Introduction: Although preclinical studies of cell delivery in models of ischemic heart failure (HF) suggest a beneficial interaction between mesenchymal stromal cells (MSCs) and c-kit+ cardiac progenitor cells (CPCs) resulting in additive therapeutic effects, no clinical trial has examined a combination of different cell types in ischemic HF. Furthermore, comparative studies of different cell products in humans are rare. CONCERT-HF (NCT02501811) is an NHLBI-sponsored, randomized, double-blind, placebo-controlled, Phase II trial of the Cardiovascular Cell Therapy Research Network (CCTRN) investigating feasibility, safety, and efficacy of MSCs and CPCs, alone and in combination, in patients with chronic ischemic HF. Objectives: To address the following questions: Is combined treatment with MSCs and CPCs feasible and safe in patients with ischemic HF? Do MSCs and CPCs, given alone or in combination, alleviate LV dysfunction, reduce scar size, improve quality of life, and/or augment functional capacity? Is either cell type more effective than the other? Is the combination of MSCs and CPCs more efficacious than MSCs alone or CPCs alone? Methods: Patients were randomized (1:1:1:1) to receive i) the combination of autologous bone marrow-derived MSCs and autologous CPCs, ii) MSCs alone, iii) CPCs alone, or iv) placebo. Target doses were 150 x 10 6 MSCs and 5 x 10 6 CPCs. All patients underwent bone marrow aspiration and right heart catheterization. Endomyocardial biopsy was performed only in the MSC + CPC and CPC alone groups; a “sham biopsy” was performed in the MSC alone and placebo groups. All patients underwent study product injection using the NOGA ® XP Mapping System and were followed for 12 months. Results: A total of 125 patients (116 M, 9 F), 62.5 ± 8.9 years old, were enrolled at 7 CCTRN centers between Nov 2016 and Oct 2018. Baseline LVEF (cardiac MRI) was 28.6 ± 6.1% with a mean scar size of 31.8 ± 10.9 g and NYHA class II (80%) or class III (15.2%). Conclusions: CONCERT-HF is the first cell therapy trial to assess a combination of different cell types and to directly compare two different cell products in patients with HF. All patients will complete follow-up by the end of June and final primary (12-month) safety and outcomes data will be available in August 2020.

Background: Electrogram (EGM) morphology recurrence (EMR) mapping of persistent atrial fibrillation (PeAF) quantifies consistency of activation at each site and is expected to be high and rapid near drivers of PeAF. Objective: To compare EMR in the left (LA) and right atrium (RA) in patients undergoing first- vs second-time PeAF catheter ablation (CA). Methods: Multisite bipolar EGM mapping of the LA (265±153 sites) and RA (224±148 sites) prior to CA for PeAF was performed in 40 patients (29 males, age 63±9 yrs, CHA2DS2-VASc 2.4±1.5, LVEF 48±12%) undergoing first (Group 1, n=31) or second-time (Group 2, n=9) CA. After cross-correlation of each automatically detected EGM with every other EGM in the recording, the most recurrent EGM morphology was identified and its frequency (Rec%) and cycle length of recurrence (CL R ) were computed (figure). The minimum CL R sites were identified. Results: In group 1, shortest CL R was in the LA in 26 patients (84%) and RA in 5 patients (16%). In the LA, there were 1 (n=23), 2 (n=2), or 3 (n=1) areas of shortest CL R , most commonly in the pulmonary veins (PV; n=19). In the RA, there was only 1 area of shortest CL R . Minimum CL R was 174.1±25.4 ms (LA-179.6±37.4 vs RA-207.9±34.5, p=0.0004), with Rec% 95±10%. In group 2, shortest CL R was in the LA in 5 patients and RA in 5 patients (56%)– one had both LA and RA. In the LA/RA, there were 1 (n=3/4) or 2 (n=2/1) areas of shortest CL R . The most common LA site was non-PV (6/7, 85.7%). The minimum CL R was 182.1±26.2ms (LA-190.8±36.2 vs RA-196.0±30.5, p=0.6), with Rec% 96±5%. Conclusion: In 61% of patients undergoing initial CA for PeAF, EMR identified LA drivers in the PVs which may explain why PV isolation has been reported to have 50-60% success rates in PeAF. In patients undergoing a 2 nd ablation for PeAF, EMR identified predominantly nonPV drivers with even distribution of shortest CL R between RA and LA and diminished CL R gradient between the LA and RA. EMR may be a useful mapping tool to characterize potential drivers of PeAF.

Background The combination of autologous mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) synergistically reduces scar size and improves cardiac function in ischemic cardiomyopathy. Whereas allogeneic (allo-)MSCs are immunoevasive, the capacity of CSCs to similarly elude the immune system remains controversial, potentially limiting the success of allogeneic cell combination therapy (ACCT). Objectives This study sought to test the hypothesis that ACCT synergistically promotes cardiac regeneration without provoking immunologic reactions. Methods Gottingen swine with experimental ischemic cardiomyopathy were randomized to receive transendocardial injections of allo-MSCs + allo-CSCs (ACCT: 200 million MSCs/1 million CSCs, n = 7), 200 million allo-MSCs (n = 8), 1 million allo-CSCs (n = 4), or placebo (Plasma-Lyte A, n = 6). Swine were assessed by cardiac magnetic resonance imaging and pressure volume catheterization. Immune response was tested by histologic analyses. Results Both ACCT and allo-MSCs reduced scar size by −11.1 ± 4.8% (p = 0.012) and −9.5 ± 4.8% (p = 0.047), respectively. Only ACCT, but not MSCs or CSCs, prevented ongoing negative remodeling by offsetting increases in chamber volumes. Importantly, ACCT exerted the greatest effect on systolic function, improving the end-systolic pressure-volume relation (+0.98 ± 0.41 mm Hg/ml; p = 0.016). The ACCT group had more phospho-histone H3+ (a marker of mitosis) cardiomyocytes (p = 0.04), and noncardiomyocytes (p = 0.0002) than did the placebo group in some regions of the heart. Inflammatory sites in ACCT and MSC-treated swine contained immunotolerant CD3+/CD25+/FoxP3+ regulatory T cells (p Conclusions ACCT demonstrates synergistic effects to enhance cardiac regeneration and left ventricular functional recovery in a swine model of chronic ischemic cardiomyopathy without adverse immunologic reaction. Clinical translation to humans is warranted.

Background Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM). Objectives The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM. Methods Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers. Results There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (>80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05). Conclusions These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625)

Introduction Both transfemoral (TF) and transapical (TA) routes are utilized for Transcatheter Aortic Valve Replacement (TAVR) using Edwards SAPIEN & SAPIEN XT valves. We intended to perform a meta-analysis comparing the complication rates between these two approaches in studies published before and after the standardized Valve Academic Research Consortium (VARC) definitions. Methods We performed a comprehensive electronic database search for studies published until January 2014 comparing TF and TA approaches using the Edwards SAPIEN/SAPIEN XT aortic valve. Studies were analyzed based on the following endpoints: 1-year mortality, 30-day mortality, stroke, new pacemaker implantation, bleeding, and acute kidney injury. Results Seventeen studies were included in the meta-analysis. Patients undergoing TA TAVR had a significantly higher logistic EuroSCORE (24.6 ± 12.9 vs. 21.3 ± 12.0; P

Right ventricular pacing (RVP) may impair left ventricular function, but is often used for advanced atrioventricular block and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP) and RVP for advanced atrioventricular block without

Background— Atrial fibrillation ablation has made tremendous progress with respect to innovation, efficacy, and safety. However, limited data exist regarding the burden and trends in adverse outcomes arising from this procedure. The aim of our study was to examine the frequency of adverse events attributable to atrial fibrillation (AF) ablation and the influence of operator and hospital volume on outcomes. Methods and Results— With the use of the Nationwide Inpatient Sample, we identified AF patients treated with catheter ablation. We investigated common complications including cardiac perforation and tamponade, pneumothorax, stroke, transient ischemic attack, vascular access complications (hemorrhage/hematoma, vascular complications requiring surgical repair, and accidental arterial puncture), and in-hospital death described with AF ablation, and we defined these complications by using validated International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes. An estimated 93 801 AF ablations were performed from 2000 to 2010. The overall frequency of complications was 6.29% with combined cardiac complications (2.54%) being the most frequent. Cardiac complications were followed by vascular complications (1.53%), respiratory complications (1.3%), and neurological complications (1.02%). The in-hospital mortality was 0.46%. Annual operator ( Conclusions— The overall complication rate was 6.29% in patients undergoing AF ablation. There was a significant association between operator and hospital volume and adverse outcomes. This suggests a need for future research into identifying the safety measures in AF ablations and instituting appropriate interventions to improve overall AF ablation outcomes.

Although human mesenchymal stem cells (hMSCs) have been tested in ischemic cardiomyopathy, few studies exist in chronic nonischemic dilated cardiomyopathy (NIDCM).The authors conducted a randomized comparison of safety and efficacy of autologous (auto) versus allogeneic (allo) bone marrow-derived hMSCs in NIDCM.Thirty-seven patients were randomized to either allo- or auto-hMSCs in a 1:1 ratio. Patients were recruited between December 2011 and July 2015 at the University of Miami Hospital. Patients received hMSCs (100 million) by transendocardial stem cell injection in 10 left ventricular sites. Treated patients were evaluated at baseline, 30 days, and 3-, 6-, and 12-months for safety (serious adverse events [SAE]), and efficacy endpoints: ejection fraction, Minnesota Living with Heart Failure Questionnaire, 6-min walk test, major adverse cardiac events, and immune biomarkers.There were no 30-day treatment-emergent SAEs. Twelve-month SAE incidence was 28.2% with allo-hMSCs versus 63.5% with auto-hMSCs (p = 0.1004 for the comparison). One allo-hMSC patient developed an elevated (80) donor-specific calculated panel reactive antibody level. The ejection fraction increased in allo-hMSC patients by 8.0 percentage points (p = 0.004) compared with 5.4 with auto-hMSCs (p = 0.116; allo vs. auto p = 0.4887). The 6-min walk test increased with allo-hMSCs by 37.0 m (p = 0.04), but not auto-hMSCs at 7.3 m (p = 0.71; auto vs. allo p = 0.0168). MLHFQ score decreased in allo-hMSC (p = 0.0022) and auto-hMSC patients (p = 0.463; auto vs. allo p = 0.172). The major adverse cardiac event rate was lower, too, in the allo group (p = 0.0186 vs. auto). Tumor necrosis factor-α decreased (p = 0.0001 for each), to a greater extent with allo-hMSCs versus auto-hMSCs at 6 months (p = 0.05).These findings demonstrated safety and clinically meaningful efficacy of allo-hMSC versus auto-hMSC in NIDCM patients. Pivotal trials of allo-hMSCs are warranted based on these results. (Percutaneous Stem Cell Injection Delivery Effects on Neomyogenesis in Dilated Cardiomyopathy [PoseidonDCM]; NCT01392625).

Tricuspid valve (TV) perforation is a rare complication after implantable cardioverter defibrillator (ICD) and permanent pacemaker implantation. In reported cases of lead-related TV perforations, patients' present with symptoms months to years postimplantation. We describe a case where a patient presented with signs of severe TV regurgitation secondary to traumatic perforation of the septal leaflet two weeks after ICD implantation and review of the literature associated with this complication.

Ablation techniques have been described for the management of symptomatic Brugada syndrome, but this treatment is still considered experimental. We performed a systematic review of the current evidence on substrate modification to manage patients with symptomatic Brugada syndrome. PubMed, Embase

Background: Sudden cardiac deaths (SCD) are important clinical end points to assess the outcomes of many cardiovascular conditions. Examination of seasonal variation of certain diseases has led to new insights into pathophysiologic triggers. We assessed the seasonal variations in SCD. Methods: The

Background: Syncope is one of the most common reasons for emergency department visits and hospitalizations. We investigated the implications of such presentations from a large volume, nation-wide perspective, particularly to determine the trends in admissions, cost, and mortality. Methods: Data

Background: The outcomes related to chest pain associated with cocaine use and its burden on healthcare system are not well studied. Methods: Data were collected from the Nationwide Inpatient Sample (2001 — 2012). Subjects were identified by using the ICD-9-CM codes. Primary outcome was a

Background: Almost 25% of patients with Chagas disease (CD) have some degree of cardiac compromise, including rhythm disturbances, which ultimately may require permanent pacemaker (PPM) implantation. CD has been shown to be an independent risk factor for mortality in heart failure. In PPM patients the prognostic significance of CD seropositivity is yet to be determined. Methods: Patients from a highly endemic region for CD with a PPM were divided into two groups: those with CD confirmed by immunofluorescence and those without CD. Patients were followed for a 3-year period. Cox proportional-hazards model and Kaplan-Meier method with log-rank test for mortality were calculated. Results: A total of 75 patients aged 65.3±12 years were included, of which 31 (41%) were males and 49 (65%) had positive serology for CD. Age, gender, diabetes, hypertension, ejection fraction, reason for PPM implantation and prior myocardial infarction were not significantly different between groups. After a 3-year follow up, 8 patients in the CD group and 1 in the control group died. Although mortality rate was higher in patients with CD seropositivity, the difference was not statistically significant (HR 3.86; p=0.17). Kaplan-Meier survival plot is illustrated bellow. Conclusions: CD was associated with a non-significant increased mortality rate in PPM patients. Larger prospective studies may reveal a significant prognostic role for CD seropositivity in this population.

Tricuspid valve (TV) perforation is a rare complication after implantable cardioverter defibrillator (ICD) and permanent pacemaker implantation. In reported cases of lead-related TV perforations, patients' present with symptoms months to years postimplantation. We describe a case where a patient presented with signs of severe TV regurgitation secondary to traumatic perforation of the septal leaflet two weeks after ICD implantation and review of the literature associated with this complication.

Cardiac conduction abnormalities, including left bundle branch block (LBBB), are not uncommon after TAVR. We aimed to evaluate the need for permanent pacemaker (PPM) insertion after development of new LBBB. This is a single center study of TAVR patients. Twelve-lead ECGs were acquired pre- and

This review discusses the treatment of ventricular arrhythmias and bradyarrhythmias. Recent studies addressing the management of nonsustained ventricular arrhythmias in patients with congestive heart failure and those recovering from myocardial infarction are discussed. Determination of the origin of wide QRS complex tachycardia is usually possible at the bedside and the diagnostic criteria are provided. Therapy to prevent recurrent ventricular tachycardia or ventricular fibrillation is difficult and controversial. A widely accepted approach based on electrophysiologic testing and implantable defibrillators appears to be the most effective. Recognition and management of common bradyarrhythmias including the indications for pacemakers are discussed.

Management of cardiac arrhythmias has undergone major changes in the last few years. In the first part of this review, general principles of arrhythmia diagnosis are discussed. New techniques such as event recording and signal-averaged electrocardiography have a significant role in the clinical management of arrhythmias. Many new antiarrhythmic drugs are now available. Suppression of premature ventricular contractions to prevent malignant ventricular arrhythmias has been demonstrated to be an ineffective strategy. Implantable defibrillators and radio frequency ablation have revolutionized the treatment of arrhythmias. Differentiation of various supraventricular tachycardias has become very important since some these arrhythmias may be cured by radiofrequency ablation. Diagnosis and treatment of common supraventricular arrhythmias are discussed.

Importance Whether culture-expanded mesenchymal stem cells or whole bone marrow mononuclear cells are safe and effective in chronic ischemic cardiomyopathy is controversial. Objective To demonstrate the safety of transendocardial stem cell injection with autologous mesenchymal stem cells (MSCs) and bone marrow mononuclear cells (BMCs) in patients with ischemic cardiomyopathy. Design, setting, and patients A phase 1 and 2 randomized, blinded, placebo-controlled study involving 65 patients with ischemic cardiomyopathy and left ventricular (LV) ejection fraction less than 50% (September 1, 2009-July 12, 2013). The study compared injection of MSCs (n=19) with placebo (n = 11) and BMCs (n = 19) with placebo (n = 10), with 1 year of follow-up. Interventions Injections in 10 LV sites with an infusion catheter. Main outcomes and measures Treatment-emergent 30-day serious adverse event rate defined as a composite of death, myocardial infarction, stroke, hospitalization for worsening heart failure, perforation, tamponade, or sustained ventricular arrhythmias. Results No patient had a treatment-emergent serious adverse events at day 30. The 1-year incidence of serious adverse events was 31.6% (95% CI, 12.6% to 56.6%) for MSCs, 31.6% (95% CI, 12.6%-56.6%) for BMCs, and 38.1% (95% CI, 18.1%-61.6%) for placebo. Over 1 year, the Minnesota Living With Heart Failure score improved with MSCs (-6.3; 95% CI, -15.0 to 2.4; repeated measures of variance, P=.02) and with BMCs (-8.2; 95% CI, -17.4 to 0.97; P=.005) but not with placebo (0.4; 95% CI, -9.45 to 10.25; P=.38). The 6-minute walk distance increased with MSCs only (repeated measures model, P = .03). Infarct size as a percentage of LV mass was reduced by MSCs (-18.9%; 95% CI, -30.4 to -7.4; within-group, P = .004) but not by BMCs (-7.0%; 95% CI, -15.7% to 1.7%; within-group, P = .11) or placebo (-5.2%; 95% CI, -16.8% to 6.5%; within-group, P = .36). Regional myocardial function as peak Eulerian circumferential strain at the site of injection improved with MSCs (-4.9; 95% CI, -13.3 to 3.5; within-group repeated measures, P = .03) but not BMCs (-2.1; 95% CI, -5.5 to 1.3; P = .21) or placebo (-0.03; 95% CI, -1.9 to 1.9; P = .14). Left ventricular chamber volume and ejection fraction did not change. Conclusions and relevance Transendocardial stem cell injection with MSCs or BMCs appeared to be safe for patients with chronic ischemic cardiomyopathy and LV dysfunction. Although the sample size and multiple comparisons preclude a definitive statement about safety and clinical effect, these results provide the basis for larger studies to provide definitive evidence about safety and to assess efficacy of this new therapeutic approach. Trial registration clinicaltrials.gov Identifier: NCT00768066.

The epidemiology of ventricular tachycardia/fibrillation (VT/VF) and sudden cardiac death (SCD) must be explored from multiple aspects, each of which contributes insights into the problem and no one of which exerts exclusive dominance for preventive or therapeutic strategies. These include: (1) population dynamics, using conventional epidemiologic approaches; (2) risk as a function of time from an index event; (3) conditioning risk factors, based on the presence of underlying disease states; (4) transient risk factors that are dynamic and trigger a potentially fatal event at a specific point in time; and (5) “response risk,” which refers to individual susceptibility (possibly determined genetically) to the adverse effects of longitudinal and/or dynamic risk factors. Major inroads into profiling individual or population risk of SCD will require better understanding of each of these epidemiologic-clinical-physiologic interactions. The disciplines range from epidemiology, through clinical medicine, to membrane channel physiology, genetic determinants, and molecular biology.

We aim to evaluate the health care associated cost of Sudden Cardiac Death (SCD) in the United States. We used the US National Inpatient Sample (2003 to 2012) to identify patients with SCD. Total health care inflation adjusted cost was the primary outcome. Overall, an estimated 1,387,396 patients

Cirrhotic patients are considered a high risk group for coronary revascularization. We assessed in-hospital mortality in these patients with myocardial infarction (MI) undergoing coronary revascularization. We used the National Inpatient Sample from 2003-2012 to identify cirrhotic patients with MI

Arrhythmias in women may be affected by phases of the menstrual cycle. This study was designed to determine the prevalence of perimenstrual clustering of spontaneous episodes of paroxysmal supraventricular tachycardia (SVT) in women. It also tested the hypothesis that women with this temporal pattern of events have an altered probability of induction of paroxysmal SVT during electrophysiologic testing at higher estrogen states (midcycle or with estrogen replacement therapy) than at low estrogen states (perimenstrual or without estrogen replacement). A structured history of the relation of spontaneous paroxysmal SVTs to phases of the menstrual cycle was obtained prospectively among 42 women referred during a 3-year period. Patients with cyclical patterns of spontaneous tachycardias, who had had negative electrophysiologic studies at midcycle or while receiving estrogen replacement therapy, had repeat procedures (1) when premenstrual or at the onset of menses, or (2) after stopping estrogen replacement therapy. Seventeen of 42 consecutive female patients (40%) had histories of perimenstrual clustering of arrhythmias. Six women (4 with normal menstrual cycles, 2 on estrogen replacement therapy), who qualified for paired electrophysiologic studies because of a negative initial electrophysiologic study that included provocation with isoproterenol, had inducibility into SVTs during the second study. All 6 had dual atrioventricular (AV) nodal pathway physiology, 4 had AV nodal reentrant tachycardia (AVNRT) induced, 1 had both AVNRT and reciprocating AV tachycardias, and 1 had nonsustained AVNRT and an atrial tachycardia induced. Successful ablation procedures were performed in 5 of the 6 patients. Thus, among women with a history of perimenstrual clustering of paroxysmal SVT and among those receiving estrogen replacement therapy, scheduling of elective electrophysiologic procedures at times of low estrogen levels (premenstrual or off estrogen replacement therapy) may facilitate the probability of a successful procedure.

The results of the Cardiac Arrhythmia Suppression Trials (CAST and CAST II) were a watershed in attitudes about management of cardiac arrhythmias.1 2 3 On the basis of the then-prevailing assumption that premature ventricular contractions (PVCs) in the presence of recent myocardial infarction identified a risk for life-threatening arrhythmias and that they also served as the trigger for fatal arrhythmias, it was logical to determine whether suppression of ambient arrhythmias would protect against fatal events.4 Despite the outcomes of these trials, ambient arrhythmias are still viewed as a marker of risk (perhaps somewhat lower than previously thought) and as pathophysiological triggers under proper conditions.5 However, the concept that suppression of asymptomatic PVCs is an appropriate preventive strategy has fallen under the weight of evidence from those studies.6 In addition, new concepts of proarrhythmia emerged from CAST and other sources of information.7 After CAST, a variety of trials testing therapy with other drugs and with implantable devices were implemented, some of which are now completed. The various trials differ in regard to therapeutic strategies, designs, and patient populations. With the flow of new information that has been forthcoming and is anticipated to continue during the next few years, it is important to keep the strengths and limitations of clinical trial designs in perspective and to consider the extent to which the results of any one trial or group of trials can be generalized. This review is intended to analyze general features of trial design that influence their interpretation, application, and clinical impact. It is not intended as a critique of individual trials. The factors discussed include (1) specific outcomes measures; (2) the type of controls used; (3) intention-to-treat versus on-therapy analysis; (4) comparison of therapeutic efficacy, efficiency, and equilibrium; (5) significant negative outcomes; and (6) population …