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Diagnostic information retrieved from a pacemaker offers the ability to improve patient care. Pacemaker diagnostic data provides information regarding pacemaker function and activity, lead function, arrhythmia occurrence, and data to aid in optimal pacemaker programming. Current pacemakers incorporate greater storage capabilities, more efficient means of storing and presenting data between follow-up visits, and more options for programming diagnostic functions and algorithms. The cardiac rhythm of the paced patient can be evaluated via real-time intracardiac electrograms at interrogation, surface electrocardiograms, ambulatory electrocardiograms, and by pacemaker stored diagnostic function that may include stored intracardiac electrograms. This article focuses on the various methods of obtaining diagnostic information regarding pacemaker activity, pacemaker function, and diagnostic information on cardiac arrhythmias. The current clinical applicability and limitations of these methods and the use of stored diagnostic data in the clinical follow-up and study of patients with pacemakers is discussed. [ABSTRACT FROM AUTHOR]

Background: Long-term anticoagulation (AC) therapy reduces the risk of stroke in patients with Atrial Fibrillation (AF). However, data on the impact of AC on in-hospital stroke outcomes is lacking., Methods: The National Inpatient Sample was used to identify adult inpatients with AF and a primary diagnosis of ischemic stroke between 2016 and 2020. Data was stratified between AC users and nonusers. A multivariate regression model was used to describe the in-hospital outcomes, adjusting for significant comorbidities., Results: A total of 655,540 hospitalizations with AF and a primary hospitalization diagnosis of ischemic stroke were included, of which 194,560 (29.7 %) were on long-term AC. Patients on AC tended to be younger (mean age, 77 vs. 78), had a higher average CHA2DS2VASc score (4.48 vs. 4.20), higher rates of hypertension (91 % vs. 88 %), hyperlipidemia (64 % vs. 59 %), and heart failure (34 % vs. 30 %) compared to patients not on long-term AC. Use of AC was associated with decreased in-hospital mortality (aOR [95 % CI]: 0.62 [0.60-0.63]), decreased stroke severity (mean NIHSS, 8 vs. 10), decreased use of tPA (aOR 0.42 [0.41-0.43]), mechanical thrombectomy (aOR 0.85 [0.83-0.87]), intracranial hemorrhage (aOR 0.69 [0.67-0.70]), gastrointestinal bleeding (aOR 0.74 [0.70-0.77]), and discharge to skilled nursing facilities (aOR 0.90 [0.89-0.91]), compared to patients not on AC (P<0.001 for all comparisons)., Conclusion: Among patients with AF admitted for acute ischemic stroke, AC use prior to stroke was associated with decreased in-hospital mortality, decreased stroke severity, decreased discharge to SNF, and fewer stroke-related and bleeding complications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Success rates for catheter ablation of atrial fibrillation (AF), particularly persistent AF, remain suboptimal. Pulmonary vein isolation has been the cornerstone for catheter ablation of AF for over a decade. While successful for most patients, pulmonary vein isolation alone is still insufficient for a substantial minority. Frustratingly, multiple clinical trials testing a diverse array of additional ablation approaches have led to mixed results, with no current strategy that improves AF outcomes beyond pulmonary vein isolation in all patients. Nevertheless, this large collection of data could be used to extract important insights regarding AF mechanisms and the diversity of the AF syndrome. Mechanistically, the general model for arrhythmogenesis prompts the need for tools to individually assess triggers, drivers, and substrates in individual patients. A key goal is to identify those who will not respond to pulmonary vein isolation, with novel approaches to phenotyping that may include mapping to identify alternative drivers or critical substrates. This, in turn, can allow for the implementation of phenotype-based, targeted approaches that may categorize patients into groups who would or would not be likely to respond to catheter ablation, pharmacological therapy, and risk factor modification programs. One major goal is to predict individuals in whom additional empirical ablation, while feasible, may be futile or lead to atrial scarring or proarrhythmia. This work attempts to integrate key lessons from successful and failed trials of catheter ablation, as well as models of AF, to suggest future paradigms for AF treatment., Competing Interests: Dr Goldberger is a co-inventor on a patent for electrogram morphology recurrence analysis. Dr Narayan is a co-inventor on intellectual property owned by University of California regents and Stanford University on atrial fibrillation mapping.

Introduction: Multiple analysis techniques evaluate electrograms during atrial fibrillation (AF), but none have been established to guide catheter ablation. This study compares electrogram properties recorded from multiple right (RA) and left atrial (LA) sites., Methods: Multisite LA/RA mapping (281 ± 176/239 ± 166 sites/patient) was performed in 42 patients (30 males, age 63 ± 9 years) undergoing first (n = 32) or redo-AF ablation (n = 10). All electrogram recordings were visually reviewed and artifactual signals were excluded leaving a total of 21 846 for analysis. Electrogram characteristics evaluated were cycle length (CL), amplitude, Shannon's entropy (ShEn), fractionation interval, dominant frequency, organizational index, and cycle length of most recurrent morphology (CL R ) from morphology recurrence plot analysis., Results: Electrogram characteristics were correlated to each other. All pairwise comparisons were significant (p < .001) except for dominant frequency and CL R (p = .59), and amplitude and dominant frequency (p = .38). Only ShEn and fractionation interval demonstrated a strong negative correlation (r = -.94). All other pairwise comparisons were poor to moderately correlated. The relationships are highly conserved among patients, in the RA versus LA, and in those undergoing initial versus redo ablations. Antiarrhythmic drug therapy did not have a significant effect on electrogram characteristics, except minimum ShEn. Electrogram characteristics associated with ablation outcome were shorter minimum CL R , lower minimum ShEn, and longer mimimum CL. There was minimal overlap between the top 10 sites identified by one electrogram characteristic and the top 10 sites identified by the other 10 characteristics., Conclusion: Multiple techniques can be employed for electrogram analysis in AF. In this analysis of eight different electrogram characteristics, seven were poorly to moderately correlated and do not identify similar locations. Only some characteristics were predictive of ablation outcome. Further studies to consider electrogram properties, perhaps in combination, for categorizing and/or mapping AF are warranted., (© 2023 The Authors. Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: There are no standard mapping approaches for patients with persistent atrial fibrillation (PeAF), particularly after failed prior catheter ablation (CA). In this study, we assess the feasibility of using Electrogram Morphology Recurrence (EMR) to guide ablation., Methods: Ten patients with recurrent PeAF after prior CA underwent detailed mapping of both atria during PeAF using the PentaRay (4 mm interelectrode spacing) and 3D mapping with CARTO. At each site, 15 s recordings were made. Custom software identified each electrogram and cross-correlation was used to identify the most recurrent electrogram morphology from which the % recurrence and cycle length of the most repeatable morphology (CL R ) was calculated. Sites of shortest CL R and sites within 5 ms of shortest CL R with recurrence ≥ 80% were used to inform CA strategy., Results: A mean of 342.9 ± 131.9 LA and 328.6 ± 91.5 RA sites were recorded per patient. Nine had PV reconnection. Shortest CL R sites guided ablation in 6/10 patients while 1 patient failed to fulfill shortest CL R criteria, and another 3 did not undergo CA guided by shortest CL R due to operator preference. On 12-month follow-up, all 4 patients without shortest CL R guided CA had recurrent PeAF. Of the 6 patients with shortest CL R guided CA, 5 patients did not have recurrent PeAF (p = 0.048), although 1 had paroxysmal AF and 2 had atypical atrial flutter., Conclusion: EMR is a feasible, novel technique to guide CA in patients with PeAF. Further evaluation is needed to provide an electrogram-based method for mapping guided targeted ablation of key areas., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms., (Copyright © 2022. Published by Elsevier Inc.)

Background: Single-chamber leadless intracardiac pacemaker (LICP) implantation was approved in 2016 in the United States. However, little is known regarding trends in real-world utilization and complication rates., Objective: The purpose of this study was to assess nationwide demographics, trends, and outcomes among hospitalizations with LICP implantation in the United States., Methods: Using the National Inpatient Sample, we identified all hospitalizations with LICP or transvenous pacemaker implantation as a comparator between 2017 and 2019. We evaluated baseline patient characteristics, admitting diagnoses, procedural complications, lengths of stay, discharge dispositions, and all-cause mortality., Results: The majority of LICP recipients were elderly (75.4 ± 12.8 years), male (55.2%), and White (76.8%) compared to Black (9.8%), or Hispanic (7.3%). Between 2017 and 2019, the average age increased along with the prevalence of heart failure, atrial fibrillation, and malignancy among recipients. Most hospitalizations were emergent (84.5%). Between 2017 and 2019, pooled procedural complications decreased significantly (10.8% vs 7.9%; P <.001), primarily due to declining infection and device retrieval rates. In-hospital mortality also decreased significantly (8.2% vs 4.2%; P <.001). History of cardiogenic shock or cardiac device infection was associated with the greatest mortality or complication risk. Compared to transvenous pacemaker, LICP implantation was associated with lower complication rates (8.6% vs 11.2%) but greater mortality (5.2% vs 1.3%; P <.001)., Conclusion: Nationwide LICP implantations were performed in patients of increasing age, comorbidities, and acuity of illness. In-hospital mortality and procedure-related complications declined in the first 3 years after approval of LICP implantation and may reflect improving operator experience. Increased mortality compared with transvenous pacemaker implant remains a concern., (Copyright © 2022 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Introduction/purpose: SARS-CoV-2 infection (COVID-19) can result in myocarditis. Protocols were developed to allow competitive athletes to safely return to play (RTP) after a COVID-19 infection, but the financial impact of these protocols is unknown. Our objective was to determine the differential cost of post-COVID-19 RTP protocols for competitive collegiate athletes., Methods: This multicenter retrospective cohort study of clinical evaluation of 295 athletes after COVID-19 infection was performed at four institutions with three RTP protocols. Costs were calculated using adjusted Center for Medicare and Medicaid Services pricing. All athletes underwent electrocardiogram and clinical evaluation. A tiered approach performed cardiac imaging and biomarker analysis for major symptoms. A universal transthoracic echocardiogram (TTE) approach performed TTE and biomarkers for all athletes. A universal exercise stress echocardiogram (ESE) approach performed ESE and biomarkers for all athletes., Results: The cost per athlete was $632.51 ± 651.80 ($44,908 total) in tiered group (n = 71), $1,072.30 ± 517.93 ($87,928 total) in the universal TTE group (n = 82), and $1357.38 ± 757.05 ($192,748 total) in the universal ESE group (n = 142) (P < 0.001). Extrapolated national costs for collegiate athletes would be $39 to 64 million higher for universal imaging approaches versus a tiered approach. Only seven athletes had probable/possible myocarditis with no significant difference between approaches., Conclusions: Cardiac screening in collegiate athletes after COVID-19 infection resulted in significant cost to the health care system. A tiered-based approach was more economical, and a universal exercise echocardiogram group detected slightly more myocardial abnormalities by cardiac magnetic resonance imaging. The clinical consequences of these approaches are unknown., (Copyright © 2022 by the American College of Sports Medicine.)

Purpose: This study assessed a functional protocol to identify myocarditis or myocardial involvement in competitive athletes following SARS-CoV2 infection., Methods: We prospectively evaluated competitive athletes (n = 174) for myocarditis or myocardial involvement using the Multidisciplinary Inquiry of Athletes in Miami (MIAMI) protocol, a median of 18.5 (IQR 16-25) days following diagnosis of COVID-19 infection. The protocol included biomarker analysis, ECG, cardiopulmonary stress echocardiography testing with global longitudinal strain (GLS), and targeted cardiac MRI for athletes with abnormal findings. Patients were followed for median of 148 days., Results: We evaluated 52 females and 122 males, with median age 21 (IQR: 19, 22) years. Five (2.9%) had evidence of myocardial involvement, including definite or probable myocarditis (n = 2). Three of the 5 athletes with myocarditis or myocardial involvement had clinically significant abnormalities during stress testing including ventricular ectopy, wall motion abnormalities and/or elevated VE/VCO2, while the other two athletes had resting ECG abnormalities. VO2 max , left ventricular ejection fraction and GLS were similar between those with or without myocardial involvement. No adverse events were reported in the 169 athletes cleared to exercise at a median follow-up of 148 (IQR108,211) days. Patients who were initially restricted from exercise had no adverse sequelae and were cleared to resume training between 3 and 12 months post diagnosis., Conclusions: Screening protocols that include exercise testing may enhance the sensitivity of detecting COVID-19 related myocardial involvement following recovery from SARS-CoV2 infection., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. The University of Miami is an equity owner in Longeveron Inc., which has licensed intellectual property from the University of Miami., (© 2022 The Authors.)

Background: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) reduce hospitalizations and death from heart failure (HF), but their effect on arrhythmia expression has been poorly investigated., Objective: The purpose of this study was to evaluate the association of SGLT2is with arrhythmias in patients with type 2 diabetes mellitus (T2DM) or HF., Methods: We searched PubMed and ClinicalTrials.gov. Two independent investigators identified randomized double-blind trials that compared SGLT2is with placebo or active control for adults with T2DM or HF. Primary outcomes were incident atrial arrhythmias, ventricular arrhythmias (VAs), and sudden cardiac death (SCD)., Results: We included 34 randomized (25 placebo-controlled and 9 active-controlled) trials with 63,166 patients (35,883 SGLT2is vs 27,273 control: mean age 53-67 years; 63% male). Medications included canagliflozin, dapagliflozin, empagliflozin, or ertugliflozin. Except for 1 study of HF, all patients had T2DM. Follow-up ranged from 24 weeks to 5.7 years. The cumulative incidence of events was low: 3.6, 1.4, and 2.5 per 1000 patient-years for atrial arrhythmias, VAs and SCD, respectively. SGLT2i therapy was associated with a significant reduction in the risk of incident atrial arrhythmias (odds ratio 0.81; 95% confidence interval 0.69-0.95; P = .008) and the "SCD" component of the SCD outcome (odds ratio 0.72; 95% confidence interval 0.54-0.97; P = .03) compared with control. There was no significant difference in incident VA or the "cardiac arrest" SCD component between groups., Conclusion: SGLT2is are associated with significantly reduced risks of incident atrial arrhythmias and SCD in patients with T2DM. Prospective trials are warranted to confirm the antiarrhythmic effect of SGLT2is and whether this is a class or drug-specific effect., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: CONCERT-HF is an NHLBI-sponsored, double-blind, placebo-controlled, Phase II trial designed to determine whether treatment with autologous bone marrow-derived mesenchymal stromal cells (MSCs) and c-kit positive cardiac cells (CPCs), given alone or in combination, is feasible, safe, and beneficial in patients with heart failure (HF) caused by ischaemic cardiomyopathy., Methods and Results: Patients were randomized (1:1:1:1) to transendocardial injection of MSCs combined with CPCs, MSCs alone, CPCs alone, or placebo, and followed for 12 months. Seven centres enrolled 125 participants with left ventricular ejection fraction of 28.6 ± 6.1% and scar size 19.4 ± 5.8%, in New York Heart Association class II or III. The proportion of major adverse cardiac events (MACE) was significantly decreased by CPCs alone (-22% vs. placebo, P = 0.043). Quality of life (Minnesota Living with Heart Failure Questionnaire score) was significantly improved by MSCs alone (P = 0.050) and MSCs + CPCs (P = 0.023) vs. placebo. Left ventricular ejection fraction, left ventricular volumes, scar size, 6-min walking distance, and peak oxygen consumption did not differ significantly among groups., Conclusions: This is the first multicentre trial assessing CPCs and a combination of two cell types from different tissues in HF patients. The results show that treatment is safe and feasible. Even with maximal guideline-directed therapy, both CPCs and MSCs were associated with improved clinical outcomes (MACE and quality of life, respectively) in ischaemic HF without affecting left ventricular function or structure, suggesting possible systemic or paracrine cellular mechanisms. Combining MSCs with CPCs was associated with improvement in both these outcomes. These results suggest potential important beneficial effects of CPCs and MSCs and support further investigation in HF patients., (© 2021 European Society of Cardiology.)

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy., (© 2021 The Authors. Published by Elsevier Inc.)

Background: Anthracycline-induced cardiomyopathy (AIC) may be irreversible with a poor prognosis, disproportionately affecting women and young adults. Administration of allogeneic bone marrow-derived mesenchymal stromal cells (allo-MSCs) is a promising approach to heart failure (HF) treatment., Objectives: SENECA (Stem Cell Injection in Cancer Survivors) was a phase 1 study of allo-MSCs in AIC., Methods: Cancer survivors with chronic AIC (mean age 56.6 years; 68% women; NT-proBNP 1,426 pg/ml; 6 enrolled in an open-label, lead-in phase and 31 subjects randomized 1:1) received 1 × 10 8 allo-MSCs or vehicle transendocardially. Primary objectives were safety and feasibility. Secondary efficacy measures included cardiac function and structure measured by cardiac magnetic resonance imaging (CMR), functional capacity, quality of life (Minnesota Living with Heart Failure Questionnaire), and biomarkers., Results: A total of 97% of subjects underwent successful study product injections; all allo-MSC-assigned subjects received the target dose of cells. Follow-up visits were well-attended (92%) with successful collection of endpoints in 94% at the 1-year visit. Although 58% of subjects had non-CMR compatible devices, CMR endpoints were successfully collected in 84% of subjects imaged at 1 year. No new tumors were reported. There were no significant differences between allo-MSC and vehicle groups with regard to clinical outcomes. Secondary measures included 6-min walk test (p = 0.056) and Minnesota Living with Heart Failure Questionnaire score (p = 0.048), which tended to favor the allo-MSC group., Conclusions: In this first-in-human study of cell therapy in patients with AIC, transendocardial administration of allo-MSCs appears safe and feasible, and CMR was successfully performed in the majority of the HF patients with devices. This study lays the groundwork for phase 2 trials aimed at assessing efficacy of cell therapy in patients with AIC.

Up to 20%-30% of patients hospitalized with coronavirus disease 2019 (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment of COVID-19 may affect the convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk of cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19-associated cardiac injury is needed. The type of testing and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of "post-COVID-19 cardiac syndrome.", (Copyright © 2020 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Sex differences impact the occurrence, presentation, prognosis, and response to therapy in heart disease. Particularly, the phenotypic presentation of patients with non-ischaemic dilated cardiomyopathy (NIDCM) differs between men and women. However, whether the response to mesenchymal stem cell (MSC) therapy is influenced by sex remains unknown. We hypothesize that males and females with NIDCM respond similarly to MSC therapy., Methods and Results: Male (n = 24) and female (n = 10) patients from the POSEIDON-DCM trial who received MSCs via transendocardial injections were evaluated over 12 months. Endothelial function was measured at baseline and 3 months post-transendocardial stem cell injection (TESI). At baseline, ejection fraction (EF) was lower (P = 0.004) and end-diastolic volume (EDV; P = 0.0002) and end-systolic volume (ESV; P = 0.0002) were higher in males vs. females. In contrast, baseline demographic characteristics, Minnesota Living with Heart Failure Questionnaire (MLHFQ), and 6-min walk test (6MWT) were similar between groups. EF improved in males by 6.2 units (P = 0.04) and in females by 8.6 units (P = 0.04; males vs. females, P = 0.57). EDV and ESV were unchanged over time. The MLHFQ score, New York Heart Association (NYHA) class, endothelial progenitor cell-colony forming units, and serum tumour necrosis factor alpha improved similarly in both groups., Conclusion: Despite major differences in phenotypic presentation of NIDCM in males and females, this study is the first of its kind to demonstrate that MSC therapy improves a variety of parameters in NIDCM irrespective of patient sex. These findings have important clinical and pathophysiologic implications regarding the impact of sex on responses to cell-based therapy for NIDCM., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

While AF most often occurs in the setting of atrial disease, current assessment and treatment of patients with AF does not focus on the extent of the atrial myopathy that serves as the substrate for this arrhythmia. Atrial myopathy, in particular atrial fibrosis, may initiate a vicious cycle in which atrial myopathy leads to AF, which in turn leads to a worsening myopathy. Various techniques, including ECG, plasma biomarkers, electroanatomical voltage mapping, echocardiography, and cardiac MRI, can help to identify and quantify aspects of the atrial myopathy. Current therapies, such as catheter ablation, do not directly address the underlying atrial myopathy. There is emerging research showing that by targeting this myopathy we can help decrease the occurrence and burden of AF., Competing Interests: Disclosure: JJG and RDM receive funding from the Miami Heart Research Institute and Grant 1R01HL145165-01 from the National Heart, Lung, and Blood Institute. HR has no conflicts of interest to declare., (Copyright © 2020, Radcliffe Cardiology.)

Introduction: Although right ventricular pacing (RVP) may impair ventricular function, it is commonly used for advanced atrioventricular block (AVB) and normal or mildly reduced ejection fraction (EF). We aimed to compare His bundle pacing (HBP), biventricular pacing (BiVP), and RVP for advanced AVB in patients with normal or mildly reduced EF., Methods and Results: MEDLINE, Embase, Cochrane CENTRAL, ClinicalTrials.gov, Scopus, and Web of Science were searched. Outcomes were all-cause death, heart failure hospitalizations (HFH), EF, left ventricular volumes, 6-minute walk test, and QRS duration. HBP or BiVP was compared with RVP. Subsequently, network meta-analysis compared the three pacing options. Our protocol was registered in PROSPERO (CRD42018094132). Six studies compared BiVP and RVP (704 vs 614 patients) and four compared HBP and RVP (463 vs 568 patients). Follow-up was 6 months to 5 years. There was significantly lower mortality and HFH with HBP or BiVP as compared with RVP (odds ratio [OR], 0.66, [0.51-0.85], P = .002; OR, 0.61 [0.45-0.82], P < .001, respectively]. HBP or BiVP also showed significant increase in EF and decrease in QRS duration (mean difference [MD], 5.27 [3.86-6.69], P < .001; MD -42.2 [-51.2 to -33.3], P < .001, respectively). In network meta-analysis, HBP and BiVP were associated with significantly improved survival compared to RVP, with surface under the cumulative ranking curve (SUCRA) probability of 79.4%, 69.4%, and 1.2% for HBP, BiVP, and RVP, respectively. For HFH, SUCRA probability was 91.5%, 57.2%, and 1.3%, respectively., Conclusion: HBP or BiVP were the superior strategies to reduce all-cause death and HFH for advanced AVB with normal or mildly reduced EF, with no significant difference between BiVP and HBP., (© 2020 Wiley Periodicals, Inc.)

Introduction: The electrophysiologic impact of cell-based therapy on the injured myocardium remains highly controversial. We aimed to perform a meta-analysis of studies comparing arrhythmia burden following transendocardial stem cell therapy vs placebo in patients with chronic ischemic heart disease (CIHD)., Methods and Results: PubMed, Embase, and Cochrane Central Register of Controlled Trials were searched. No restriction of stem cell type was specified. The outcomes included sustained supraventricular or ventricular arrhythmias (VAs), sudden cardiac death (SCD), and resuscitated sudden cardiac arrest (SCA). Effect sizes were reported as odds ratio (OR) and 95% CI. Poisson regression was used to account for zero-events data. Twelve randomized trials that included 736 patients (384 in the cell therapy group and 352 in the placebo group) were analyzed. Six different cell types were used. Follow-up ranged from 6 to 12 months. There was a significant decrease in risk of SCD in the cell therapy group, (FE OR, 0.19 [0.04, 0.93]; P = .04). In subgroup analysis, there was a significantly lower risk of SCD or resuscitated SCA in the cell therapy group limited to studies that did not use skeletal myoblasts, (FE OR, 0.23 [0.06, 0.83]; P = .03). There was no significant difference in the incidence of sustained VA between groups (FE OR, 0.91 [0.47, 1.77]; P = .8), even after stratifying by cell type. There was no difference in supraventricular arrhythmias between groups., Conclusion: Nonskeletal myoblast transendocardial cell therapy was associated with a significantly lower risk of SCD or resuscitated SCA compared to control, with no proarrhythmic effects., (© 2019 Wiley Periodicals, Inc.)

Background: Ablation approaches have been described for the management of symptomatic ventricular arrhythmias in patients with Brugada syndrome, but this treatment is still considered experimental., Objective: We aimed to perform a systematic review of the current evidence on the use of catheter ablation in Brugada syndrome., Methods: MEDLINE, Embase, and Scopus were searched for articles describing the use of catheter ablation for ventricular arrhythmia management in Brugada syndrome., Results: We included 11 case series and 11 case reports including a total of 233 patients. Ablation strategies included epicardial mapping with substrate modification (n = 180; 77.3%), endocardial-only mapping with substrate modification (n = 17; 7.3%), ventricular fibrillation (VF)-triggering premature ventricular complex ablation (n = 5; 2.1%), and mixed approaches (n = 31; 13.3%). During a 2.5- to 78-month follow-up period, the success rates in preventing ventricular tachycardia or VF (VT/VF) were 96.7%, 70.6%, and 80% with epicardial, endocardial, and triggering premature ventricular complex ablation approaches, respectively. Among patients who underwent both epicardial and endocardial mapping, there was no identifiable endocardial substrate in 92.9% of cases. Elimination of type 1 Brugada-pattern electrocardiogram was attained in 98.3% and 34.8% of the epicardial and endocardial ablation groups, respectively. VT/VF occurred in 7 of 9 patients (77.8%) who had persistent or recurrent J-ST elevation and in none of the 24 patients with complete resolution during follow-up. Pharmacologic provocation augmented the abnormal area., Conclusion: Epicardial substrate modification appears to be more effective than endocardial-only approach in preventing VT/VF. Persistent or recurrent J-ST elevation appears to represent a marker of failure of ablation. Ablation seems to be an acceptable strategy for patients with Brugada syndrome and VT/VF., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Rationale: Autologous bone marrow mesenchymal stem cells (MSCs) and c-kit + cardiac progenitor cells (CPCs) are 2 promising cell types being evaluated for patients with heart failure (HF) secondary to ischemic cardiomyopathy. No information is available in humans about the relative efficacy of MSCs and CPCs and whether their combination is more efficacious than either cell type alone., Objective: CONCERT-HF (Combination of Mesenchymal and c-kit + Cardiac Stem Cells As Regenerative Therapy for Heart Failure) is a phase II trial aimed at elucidating these issues by assessing the feasibility, safety, and efficacy of transendocardial administration of autologous MSCs and CPCs, alone and in combination, in patients with HF caused by chronic ischemic cardiomyopathy (coronary artery disease and old myocardial infarction)., Methods and Results: Using a randomized, double-blinded, placebo-controlled, multicenter, multitreatment, and adaptive design, CONCERT-HF examines whether administration of MSCs alone, CPCs alone, or MSCs+CPCs in this population alleviates left ventricular remodeling and dysfunction, reduces scar size, improves quality of life, or augments functional capacity. The 4-arm design enables comparisons of MSCs alone with CPCs alone and with their combination. CONCERT-HF consists of 162 patients, 18 in a safety lead-in phase (stage 1) and 144 in the main trial (stage 2). Stage 1 is complete, and stage 2 is currently randomizing patients from 7 centers across the United States., Conclusions: CONCERT-HF will provide important insights into the potential therapeutic utility of MSCs and CPCs, given alone and in combination, for patients with HF secondary to ischemic cardiomyopathy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02501811., (© 2018 American Heart Association, Inc.)

Background: This study was designed to estimate the costs of index hospitalizations after cardiac arrest in the United States., Methods and Results: We used the US Nationwide Inpatient Sample (2003-2012) to identify patients with cardiac arrest. Log transformation of inflation-adjusted cost was determined for care to patient outcomes. Overall, an estimated 1 387 396 patients were hospitalized after cardiac arrest. The mean age of the cohort was 66 years, 45% were women, and the majority were white. Inpatient procedures included coronary angiography (15%), percutaneous coronary intervention (7%), intra-aortic balloon pump (4.4%), therapeutic hypothermia (1.1%), and mechanical circulatory support (0.1%). The rates of therapeutic hypothermia increased from zero in 2003 to 2.7% in 2012 ( P <0.001). Both hospital charges and inflation-adjusted cost increased linearly over time. In a multivariate analysis, predictors of inflation-adjusted cost included large hospital size, urban teaching hospital, and length of stay. Among comorbidities, atrial fibrillation or fluid and electrolytes imbalance was most associated with cost. Among selected interventions, the cost was significantly increased with automatic implantable cardioverter defibrillators (odds ratio, 1.83; P <0.001), intra-aortic balloon pump (odds ratio, 1.50; P <0.001), hypothermia (odds ratio, 1.28; P <0.001), and extracorporeal membrane oxygenation (odds ratio, 2.38; P <0.001)., Conclusions: In the period between 2003 and 2012, postcardiac arrest hospitalizations resulted in a steady rise in associated health care cost, likely related to increased length of stay, medical procedures, and systems of care. Although targeted cost containment for postarrest interventions may reduce the finance burden, there is an increasing need for funding research into prediction and prevention of cardiac arrest, which offers greater societal benefit., (© 2018 American Heart Association, Inc.)

Rationale: Cell dose and concentration play crucial roles in phenotypic responses to cell-based therapy for heart failure., Objective: To compare the safety and efficacy of 2 doses of allogeneic bone marrow-derived human mesenchymal stem cells identically delivered in patients with ischemic cardiomyopathy., Methods and Results: Thirty patients with ischemic cardiomyopathy received in a blinded manner either 20 million (n=15) or 100 million (n=15) allogeneic human mesenchymal stem cells via transendocardial injection (0.5 cc per injection × 10 injections per patient). Patients were followed for 12 months for safety and efficacy end points. There were no treatment-emergent serious adverse events at 30 days or treatment-related serious adverse events at 12 months. The Major Adverse Cardiac Event rate was 20.0% (95% confidence interval [CI], 6.9% to 50.0%) in 20 million and 13.3% (95% CI, 3.5% to 43.6%) in 100 million ( P =0.58). Worsening heart failure rehospitalization was 20.0% (95% CI, 6.9% to 50.0%) in 20 million and 7.1% (95% CI, 1.0% to 40.9%) in 100 million ( P =0.27). Whereas scar size reduced to a similar degree in both groups: 20 million by -6.4 g (interquartile range, -13.5 to -3.4 g; P =0.001) and 100 million by -6.1 g (interquartile range, -8.1 to -4.6 g; P =0.0002), the ejection fraction improved only with 100 million by 3.7 U (interquartile range, 1.1 to 6.1; P =0.04). New York Heart Association class improved at 12 months in 35.7% (95% CI, 12.7% to 64.9%) in 20 million and 42.9% (95% CI, 17.7% to 71.1%) in 100 million. Importantly, proBNP (pro-brain natriuretic peptide) increased at 12 months in 20 million by 0.32 log pg/mL (95% CI, 0.02 to 0.62; P =0.039), but not in 100 million (-0.07 log pg/mL; 95% CI, -0.36 to 0.23; P =0.65; between group P =0.07)., Conclusions: Although both cell doses reduced scar size, only the 100 million dose increased ejection fraction. This study highlights the crucial role of cell dose in the responses to cell therapy. Determining optimal dose and delivery is essential to advance the field, decipher mechanism(s) of action and enhance planning of pivotal Phase III trials., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02013674., (© 2017 American Heart Association, Inc.)

Background: The outcomes related to chest pain associated with cocaine use and its burden on the healthcare system are not well studied., Methods: Data were collected from the Nationwide Inpatient Sample (2001-2012). Subjects were identified by using the International Classification of Diseases, Ninth Revision, Clinical Modification codes. Primary outcome was a composite of mortality, myocardial infarction, stroke, and cardiac arrest., Results: We identified 363,143 admissions for cocaine-induced chest pain. Mean age was 44.9 (±21.1) years with male predominance. Left heart catheterizations were performed in 6.7%, whereas the frequency of acute myocardial infarction and percutaneous coronary interventions were 0.69% and 0.22%, respectively. The in-hospital mortality was 0.09%, and the primary outcome occurred in 1.19% of patients. Statistically significant predictors of primary outcome included female sex (odds ratio [OR], 1.16; confidence interval [CI], 1.00-1.35; P = .046), age >50 years (OR, 1.24, CI, 1.07-1.43; P = .004), history of heart failure (OR, 1.63, CI, 1.37-1.93; P <.001), supraventricular tachycardia (OR, 2.94, CI, 1.34-6.42; P = .007), endocarditis (OR, 3.5, CI, 1.50-8.18, P = .004), tobacco use (OR, 1.3, CI, 1.13-1.49; P <.001), dyslipidemia (OR, 1.5, CI, 1.29-1.77; P <.001), coronary artery disease (OR, 2.37, CI, 2.03-2.76; P <.001), and renal failure (OR, 1.27, CI, 1.08-1.50; P = .005). The total annual projected economic burden ranged from $155 to $226 million with a cumulative accruement of more than $2 billion over a decade., Conclusion: Hospital admissions due to chest pain and concomitant cocaine use are associated with low rates of adverse outcomes. For the low-risk cohort in whom acute coronary syndrome has been ruled out, hospitalization may not be beneficial and may result in unnecessary cardiac procedures., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Transendocardial stem cell injection in patients with ischemic cardiomyopathy (ICM) improves left ventricular function and structure but has ill-defined effects on ventricular arrhythmias. We hypothesized that mesenchymal stem cell (MSC) implantation is not proarrhythmic. Post hoc analyses were performed on ambulatory ECGs collected from the POSEIDON and TAC-HFT trials. Eighty-eight subjects (mean age 61 ± 10 years) with ICM (mean EF 32.2% ± 9.8%) received treatment with MSC (n = 48), Placebo (n = 21), or bone marrow mononuclear cells (BMC) (n = 19). Heart rate variability (HRV) and ventricular ectopy (VE) were evaluated over 12 months. VE did not change in any group following MSC implantation. However, in patients with ≥ 1 VE run (defined as ≥ 3 consecutive premature ventricular complexes in 24 hours) at baseline, there was a decrease in VE runs at 12 months in the MSC group (p = .01), but not in the placebo group (p = .07; intergroup comparison: p = .18). In a subset of the MSC group, HRV measures of standard deviation of normal intervals was 75 ± 30 msec at baseline and increased to 87 ± 32 msec (p =.02) at 12 months, and root mean square of intervals between successive complexes was 36 ± 30 msec and increased to 58.2 ± 50 msec (p = .01) at 12 months. In patients receiving MSCs, there was no evidence for ventricular proarrhythmia, manifested by sustained or nonsustained ventricular ectopy or worsened HRV. Signals of improvement in ventricular arrhythmias and HRV in the MSC group suggest a need for further studies of the antiarrhythmic potential of MSCs. Stem Cells Translational Medicine 2017;6:1366-1372., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Differences in implantable cardioverter defibrillator (ICD) utilization based on insurance status have been described, but little is known about postimplant follow-up patterns associated with insurance status and outcomes. We collected demographic, clinical, and device data from 119 consecutive patients presenting with ICD shocks. Insurance status was classified as uninsured/Medicaid (uninsured) or private/Health Maintenance Organization /Medicare (insured). Shock frequencies were analyzed before and after a uniform follow-up pattern was implemented regardless of insurance profile. Uninsured patients were more likely to present with an inappropriate shock (63% vs 40%, p = 0.01), and they were more likely to present with atrial fibrillation (AF) as the shock trigger (37% vs 19%, p = 0.04). Uninsured patients had a longer interval between previous physician contact and index ICD shock (147 ± 167 vs 83 ± 124 days, p = 0.04). Patients were followed for a mean of 521 ± 458 days after being enrolled in a uniform follow-up protocol, and there were no differences in the rate of recurrent shocks based on insurance status. In conclusion, among patients presenting with an ICD shock, underinsured/uninsured patients had significantly longer intervals since previous physician contact and were more likely to present with inappropriate shocks and AF, compared to those with private/Medicare coverage. After the index shock, both groups were followed uniformly, and the differences in rates of inappropriate shocks were mitigated. This observation confirms the importance of regular postimplant follow-up as part of the overall ICD management standard., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: Radiofrequency (RF) and cryoballoon (CB) catheter ablation are effective for pulmonary vein isolation (PVI) in atrial fibrillation (AF). This report presents an updated meta-analysis comparing the efficacy and safety of CB versus RF ablations in AF., Methods: Databases and conference abstracts were systematically searched for studies that directly compared CB and RF PVI, and reported safety or efficacy outcomes in follow-up ≥12 months. Recurrent atrial tachyarrhythmias (AT) were defined as AF, atrial flutter, or atrial tachycardia., Results: Twenty-two studies and 8,668 patients were included. Freedom from AT was not significantly different between CB and RF ablations in the pooled population (OR 1.12; 95%CI 0.97-1.29; P = 0.13) and in randomized trials (OR 1.0; 95%CI 0.65-1.56; P = 0.99). Second-generation CB (CB2; 78.1%) and contact-force (CF) sensing RF (78.2%) have improved procedure success rate as compared to first-generation technology (57.9% CB, 58.1% RF). As compared to CF-RF, CB2 demonstrated similar freedom from recurrent AT (OR 1.04; 95%CI 0.71-1.51; P = 0.84). The incidence of pericardial effusions (OR 0.44; 95%CI 0.28-0.69; P < 0.01), tamponade (OR 0.31; 95%CI 0.15-0.64; P < 0.01), and non-AF AT (OR 0.46; 95%CI 0.26-0.83; P < 0.01) were significantly lower with CB ablation, whereas transient phrenic nerve palsy was more incident after CB (OR 7.40; 95%CI 2.56-21.34; P < 0.01)., Conclusion: There was comparable freedom from AT between CB and RF in patients with AF undergoing PVI. Additionally, freedom from AT was similar between CB2 and CF-RF. However, CB was associated with a lower incidence of pericardial effusions or tamponade, albeit with a higher rate of transient phrenic nerve palsies., (© 2016 Wiley Periodicals, Inc.)

Catheter ablation for atrial fibrillation (AF) has emerged as a popular procedure. The purpose of this study was to examine whether there exist differences or disparities in ablation utilization across gender, socioeconomic class, insurance, or race. Using the Nationwide Inpatient Sample (2000 to 2012), we identified adults hospitalized with a principal diagnosis of AF by ICD 9 code 427.31 who had catheter ablation (ICD 9 code-37.34). We stratified patients by race, insurance status, age, gender, and hospital characteristics. A hierarchical multivariate mixed-effect model was created to identify the independent predictors of AF ablation. Among an estimated total of 3,508,122 patients (extrapolated from 20% Nationwide Inpatient Sample) hospitalized with a diagnosis of AF in the United States from the year 2000 to 2012, 102,469 patients (2.9%) underwent catheter ablations. The number of ablations was increased by 940%, from 1,439 in 2000 to 15,090 in 2012. There were significant differences according to gender, race, and health insurance status, which persisted even after adjustment for other risk factors. Female gender (0.83 [95% CI 0.79 to 0.87; p <0.001]), black (0.49 [95% CI 0.44 to 0.55; p <0.001]), and Hispanic race (0.64 [95% CI 0.56 to 0.72; p <0.001]) were associated with lower likelihoods of undergoing an AF ablation. Medicare (0.93, 0.88 to 0.98, <0.001) or Medicaid (0.67, 0.59 to 0.76, <0.001) coverage and uninsured patients (0.55, 0.49 to 0.62, <0.001) also had lower rates of AF ablation compared to patients with private insurance. In conclusion we found differences in utilization of catheter ablation for AF based on gender, race, and insurance status that persisted over time., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background/objectives: Chagas' disease (CD) has been associated with atrial fibrillation (AF) and electrocardiographic (ECG) conduction defects. However, prior studies have shown conflicting results. We performed a meta-analysis comparing the prevalence of AF and conduction abnormalities between CD and non-CD patients., Methods: PubMed, EMBASE, Cochrane Central, and Latin American databases were searched for studies that directly compared the prevalence of AF and conduction defects in CD and non-CD patients. Odds ratios (OR) were computed using random-effects model due to anticipated heterogeneity. We further performed subanalyses limited to studies that included only patients with cardiomyopathy., Results: A total of 17,238 patients from 30 studies were included, of whom 6,840 (40%) had a positive serology for CD. In the pooled data, AF was significantly more prevalent in the CD group (OR 1.62; 95%CI 1.21-2.15; P = 0.001). However, no significant difference was observed between groups when the analysis included only patients with cardiomyopathy (OR 1.21; 95%CI 0.97-1.50; P = 0.08) or heart failure (OR 1.09; 95%CI 0.81-1.47; P = 0.55). The combination of right bundle branch block (RBBB) and left anterior fascicular block (LAFB) had the highest OR for increased prevalence in patients with Chagas' cardiomyopathy compared to non-CD etiologies (OR 5.31; 95%CI 1.23-22.86; P = 0.03)., Conclusions: Our meta-analysis suggests that the prevalence of AF in patients with Chagas' cardiomyopathy is not significantly different from non-CD cardiomyopathies. The pattern of RBBB and LAFB in patients with cardiomyopathy of unknown etiology and epidemiologic risk factors should raise the possibility of CD and prompt specific diagnostic testing., (© 2015 Wiley Periodicals, Inc.)

Prior studies have highlighted disparities in cardiac lifesaving procedure utilization, particularly among women and in minorities. Although there has been a significant increase in implantable cardioverter-defibrillator (ICD) insertion, socioeconomic disparities still exist in the trend of ICD utilization. With the use of the Nationwide Inpatient Sample from 2003 through 2011, we identified subjects with ICD insertion (procedure code 37.94) and cardiac resynchronization defibrillator (procedure code 00.50, 00.51) as codified by the International Classification of Diseases, Ninth Revision, Clinical Modification. Overall, 1 020 076 ICDs were implanted in the United States from 2003 to 2011. We observed an initial increase in ICD utilization by 51%, from 95 062 in 2003 to 143 262 in 2006, followed by a more recent decline. The majority of ICDs were implanted in men age ≥65 years. Implantation of ICDs was 2.5× more common in men than in women (402 per million vs 163 per million). Approximately 95% of the ICDs were implanted in insured patients, and 5% were used in the uninsured population. There has been a significant increase in ICD implantation in blacks, from 162 per million in 2003 to 291 per million in 2011. We found a significant difference in the volume of ICD implants between the insured and the uninsured patient populations. Racial disparities have narrowed significantly in comparison with those noted in earlier studies and are now more reflective of the population demographics at large. On the other hand, significant gender disparities continue to exist., (© 2016 Wiley Periodicals, Inc.)

Recent advances in the field of sudden cardiac death (SCD) include the recognition that 50% of SCD occurs as initial presentation of any heart disease and that many of these individuals may have been considered to be low risk. The presenting dysrhythmia in patients with cardiac arrests has changed over time such that pulseless electrical activity and asystole is more frequently encountered as compared with ventricular tachyarrhythmias. While the use of implantable defibrillators has been a tremendous advance in patients at risk for ventricular tachyarrhythmias, the use of automatic external defibrillators and wearable defibrillators is a recent advance that allows for potential SCD prevention in more patients. Finally, the area of medical genetics is an evolving discipline, which may enable clinicians to better individualize therapy for patients with genetic predispositions to cardiac dysrhythmias., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: There are limited data on prognosis and outcomes of patients with new-onset atrial fibrillation (AF) compared with those with a prior history of AF., Methods and Results: We conducted a comparison of these 2 groups in the AFFIRM trial. New-onset AF was the qualifying arrhythmia in 1,391 patients (34%). Compared with patients with prior history of AF, patients with new-onset AF were more likely to have a history of heart failure. There was no mortality difference between rate control (RaC) and rhythm control (RhC) among patients with new-onset AF (17% vs 20%, P = .152). In the univariate model, new-onset AF was associated with increased risk of mortality compared with history of prior AF (RaC unadjusted hazard ratio [HR] 1.36 [P = .010], RhC unadjusted HR 1.39 [P = .003]). However, after multivariate adjustments, new-onset AF did not carry an increased risk of mortality (RaC adjusted HR 1.14 [P = .370], RhC adjusted HR 1.16 [P = .248]). Subjects with new-onset AF randomized to the RhC arm were more likely to remain in normal sinus rhythm at follow-up (adjusted HR 0.79, P = .012) compared with patients with prior history of AF., Conclusions: In a multivariable analysis adjusting for confounders, new-onset AF was not associated with increased mortality compared with prior history of AF regardless of the treatment strategy. Patients with new-onset AF treated with the rhythm control strategy were more likely to remain in normal sinus rhythm on follow-up., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Many medications used to treat atrial fibrillation (AF) also reduce blood pressure (BP). The relation between BP and mortality is unclear in patients with AF. We performed a post hoc analysis of 3,947 participants from the Atrial Fibrillation Follow-Up Investigation of Rhythm Management trial. Systolic blood pressure (SBP) and diastolic blood pressure (DBP) at baseline and follow-up were categorized by 10-mm Hg increments. The end points were all-cause mortality (ACM) and secondary outcome (combination of ACM, ventricular tachycardia and/or fibrillation, pulseless electrical activity, significant bradycardia, stroke, major bleeding, myocardial infarction, and pulmonary embolism). SBP and DBP followed a "U-shaped" curve with respect to primary and secondary outcomes after multivariate analysis. A nonlinear Cox proportional hazards model showed that the incidence of ACM was lowest at 140/78 mm Hg. Subgroup analyses revealed similar U-shaped curves. There was an increased ACM observed with BP <110/60 mm Hg (hazard ratio 2.4, p <0.01, respectively, for SBP and DBP). In conclusion, in patients with AF, U-shaped relation existed between BP and ACM. These data suggest that the optimal BP target in patients with AF may be greater than the general population and that pharmacologic therapy to treat AF may be associated with ACM or adverse events if BP is reduced to <110/60 mm Hg., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Transient variations in physiological parameters may forewarn of life-threatening cardiac events, but are difficult to identify clinically. Implantable cardioverter defibrillators (ICD) designed to measure transthoracic impedance provide a surrogate marker for pulmonary congestion., Objective: The aim of this study is to determine if the frequency of changes in transthoracic impedance (TTI) is associated with congestive heart failure (CHF) exacerbation and predicts mortality., Methods: We followed 109 consecutive patients (pts) with ICDs (n=58) or CRT-ICDs (n=51) for a mean of 21.3 (+10.2) months. Using 80 ohm-days as a reference, we correlated the frequency of TTI changes above this index to CHF hospitalizations or death., Results: There was at least one TTI threshold crossing in 79 (72%) pts over 23.3 months follow-up, with a mean of 1.8 ± 3.4 per year. There were 18 pts with CHF hospitalizations who had a mean of 4.3 TTI threshold crossings/year (S.D.=±7.3; median=2.8), compared to 1.3 (S.D.=±1.5; median=0.8) among pts without CHF hospitalizations (p=0.0006). Among 20 patients who died during follow-up, there were 4.2 (S.D.=±7.0; median=2.9) TTI threshold crossings/year, compared with 1.3 (S.D.=±1.3; median=0.9) threshold crossings/year among survivors (p=0.0004). Using Cox Proportional Hazard modeling, after adjusting for age, baseline EF, and number of shocks, TTI threshold crossing was an independent predictor of death (HR 1.72, 95% CI 1.26-2.36, p=0.001)., Conclusions: Increased frequency of TTI threshold crossings may be a useful predictor of transient risk for identifying a subgroup of ICD recipients at greater individual risk for death or CHF hospitalizations., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) patients with left ventricular hypertrophy (LVH) and diastolic dysfunction may derive benefit from being in sinus rhythm but no data are available to support this strategy in them. We sought to investigate effect of left ventricular remodeling on cardiovascular outcomes in AF patients undergoing rhythm control strategy., Methods: We identified 1088 patients with echocardiographic data on left ventricular mass (LVM) enrolled in the AFFIRM trial. Using the American Society of Echocardiography (ASE) criteria, patients were divided into 4 categories: 1) normal geometry, 2) concentric remodeling, 3) eccentric hypertrophy, and 4) concentric hypertrophy. The primary endpoint was AF recurrence and the secondary endpoint was cardiovascular hospitalization (CVH)., Results: In rhythm control arm, median time to recurrence in patients with concentric LVH was 13.3 months (95% CI 8.2-24.5) vs. 28.3 months (95% CI 20.2-48.6) in patients without LVH. Concentric left ventricular hypertrophy (LVH) was independently predictive of AF recurrence (HR 1.49, 95% CI 1.10-2.01, p=0.01) in rhythm control arm, but not in overall population or rate control arm. Both concentric and eccentric LVH were independently predictive of cardiovascular hospitalization (CVH) in the overall population, with respective HRs of 1.36 (1.04-1.78, p=0.03) and 1.38 (1.02-1.85, p=0.04)., Conclusion: Concentric LVH is predictive of AF recurrences when a predominantly pharmacologic rhythm-control strategy is employed. Different patterns of LVH seem to be important determinants of outcomes (AF recurrence and CVH). These findings may have important clinical implications for the management of patients with AF and LVH. Further studies are warranted to confirm our findings., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia. The associated morbidity and mortality make AF a major public health burden. Hospitalizations account for the majority of the economic cost burden associated with AF. The main objective of this study is to examine the trends of AF-related hospitalizations in the United States and to compare patient characteristics, outcomes, and comorbid diagnoses., Methods and Results: With the use of the Nationwide Inpatient Sample from 2000 through 2010, we identified AF-related hospitalizations using International Classification of Diseases, 9th Revision, Clinical Modification code 427.31 as the principal discharge diagnosis. Overall AF hospitalizations increased by 23% from 2000 to 2010, particularly in patients ≥65 years of age. The most frequent coexisting conditions were hypertension (60.0%), diabetes mellitus (21.5%), and chronic pulmonary disease (20.0%). Overall in-hospital mortality was 1%. The mortality rate was highest in the group of patients ≥80 years of age (1.9%) and in the group of patients with concomitant heart failure (8.2%). In-hospital mortality rate decreased significantly from 1.2% in 2000 to 0.9% in 2010 (29.2% decrease; P<0.001). Although there was no significant change in mean length of stay, mean cost of AF hospitalization increased significantly from $6410 in 2001 to $8439 in 2010 (24.0% increase; P<0.001)., Conclusions: Hospitalization rates for AF have increased exponentially among US adults from 2000 to 2010. The proportion of comorbid chronic diseases has also increased significantly. The last decade has witnessed an overall decline in hospital mortality; however, the hospitalization cost has significantly increased., (© 2014 American Heart Association, Inc.)

Objectives: This study sought to determine the incidence of new-onset atrial fibrillation (AF) associated with different methods of isolated aortic valve replacement (AVR)-transfemoral (TF), transapical (TA), and transaortic (TAo) catheter-based valve replacement and conventional surgical approaches., Background: The relative incidences of AF associated with the various access routes for AVR have not been well characterized., Methods: In this single-center, retrospective cohort study, we evaluated a total of 231 consecutive patients who underwent AVR for degenerative aortic stenosis (AS) between March 2010 and September 2012. Patients with a history of paroxysmal, persistent, or chronic AF, with bicuspid aortic valves, and patients who died within 48 h after AVR were excluded. A total of 123 patients (53% of total group) qualified for inclusion. Data on documented episodes of new-onset AF, along with all clinical, echocardiographic, procedural, and 30-day follow-up data, were collated., Results: AF occurred in 52 patients (42.3%). AF incidence varied according to the procedural method. AF occurred in 60% of patients who underwent surgical AVR (SAVR), in 53% after TA-TAVR, in 33% after TAo-TAVR cases, and 14% after TF-TAVR. The episodes occurred at a median time interval of 53 (25th to 75th percentile, 41 to 87) h after completion of the procedure. Procedures without pericardiotomy had an 82% risk reduction of AF compared with those with pericardiotomy (adjusted odds ratio: 0.18; 95% confidence interval: 0.05 to 0.59)., Conclusions: AF was a common complication of AVR with a cumulative incidence of >40% in elderly patients with degenerative AS who underwent either SAVR or TAVR. AF was most common with SAVR and least common with TF-TAVR. Procedures without pericardiotomy were associated with a lower incidence of AF., (Copyright © 2014 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Although left ventricular (LV) hypertrophy has been proposed as a factor predisposing to atrial fibrillation (AF), its relevance to prognosis and selection of therapeutic strategies is unclear. We identified 2,105 patients with echocardiographic data on LV mass enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. LV hypertrophy was defined as increased LV mass, stratified by American Society of Echocardiography criteria. The primary end point was all-cause mortality, secondary end point was as per AFFIRM trial definition, and tertiary end point was cardiovascular hospitalizations. We compared "strict" versus "lenient" rate control in patients with increased LV mass, and studied association of heart failure (HF) with preserved and decreased systolic function in patients with increased LV mass. Over 6 years, 332 deaths (15.7%) were reported. Adjusted hazard ratio (HR) of severely increased LV mass for all-cause mortality was 1.34 (95% confidence interval [CI] 1.01 to 1.79, p=0.045) for the overall population and 1.61 (95% CI 1.09 to 2.37, p=0.016) for the rhythm-control arm. Increased LV mass was a predictor of cardiovascular hospitalizations in the lenient rate-control group (HR 1.72, 95% CI 1.05 to 2.82, p=0.03) but not in the strict rate-control group. Severely increased LV mass was predictive of cardiovascular hospitalizations in patients with HF with preserved (HR 1.8, 95% CI 1.0 to 3.2, p=0.03) and decreased LV systolic function (HR 2.4, 95% CI 1.1 to 5.2, p=0.02). Thus, LV hypertrophy is a significant independent predictor of mortality in patients with AF, especially those managed with rhythm control. In patients with LV hypertrophy, strict rate control may be associated with better outcomes than lenient rate control. LV hypertrophy portends higher cardiovascular morbidity in patients with AF and HF., (Copyright © 2014 Elsevier Inc. All rights reserved.)