Predictors of myocardial recovery in arrhythmia-induced cardiomyopathy: A multicenter study.

BACKGROUND: Arrhythmia-induced cardiomyopathy (AIC) is characterized by improvement in left ventricular ejection fraction (LVEF) following arrhythmia treatment. Predictors of recovery in LVEF are not well understood. OBJECTIVE: We evaluated predictors of AIC recovery in a large multicenter cohort. METHODS: In total, 243 patients (age 65 ± 11, 73% male) with AIC caused by atrial fibrillation (49%), atrial tachycardia (20%), and premature ventricular contractions (PVCs; 31%) were treated and included. LVEF was assessed before and after treatment. Patients were stratified by arrhythmia duration (known [KN, n = 132] vs. unknown [UKN, n = 111]), arrhythmia type, LVEF, and presence of structural heart disease (SHD). RESULTS: Arrhythmia treatment was rhythm control in 95%. Median arrhythmia duration in the KN group was 47 months (25-75th percentile, 24-80 months). Post treatment LVEF was higher in KN group (55.9 ± 7 vs. 46.2 ± 12%; p < .0001) but the degree of LVEF improvement was similar (21.2 ± 9 vs. 19.4 ± 11; p = .16). Comparing highest quartile (longest arrhythmia duration) versus the rest of the KN group, the extent of LVEF improvement was similar (21.5 ± 8 vs. 21 ± 9%; p = .1). Patients in lowest index LVEF quartile (n = 74) had more PVC-induced AIC, greater EF improvement after treatment (24 ± 17 vs. 19 ± 7%; p < .0001) but lower post treatment EF (45 ± 14 vs. 54 ± 8%; p < .0001) versus other patients. Patients with SHD had lower index EF (28 ± 8 vs. 34 ± 8%; p < .0001) and lower final EF (47 ± 12 vs. 56 ± 7; p ≪ .0001). In multivariate regression, low index LVEF predicted myocardial recovery (odds ratio, 11.4; p < .005). CONCLUSIONS: In this AIC cohort, LVEF improved regardless of arrhythmia duration or type but those with PVCs had lower index LVEF and had less recovery. Low index LVEF predicted LVEF recovery following arrhythmia treatment.

Sex-based differences in procedural complications associated with atrial fibrillation catheter ablation: A systematic review and meta-analysis.

BACKGROUND: Women undergoing atrial fibrillation catheter ablation (AFCA) have higher rates of vascular complications and major bleeding. However, most studies have been underpowered to detect differences in rarer complications such as stroke/transient ischemic attack (TIA) and procedural mortality. METHODS: We performed a systematic review of databases (PubMed, World of Science, and Embase) to identify studies published since 2010 reporting AFCA complications by sex. Six complications of interest were (1) vascular/groin complications; (2) pericardial effusion/tamponade; (3) stroke/TIA; (4) permanent phrenic nerve injury; (5) major bleeding; and (6) procedural mortality. For meta-analysis, random effects models were used when heterogeneity between studies was ≥50% (vascular complications and major bleeding) and fixed effects models for other endpoints. RESULTS: Of 5716 citations, 19 studies met inclusion criteria, comprising 244,353 patients undergoing AFCA, of whom 33% were women. Women were older (65.3 ± 11.2 vs. 60.4 ± 13.2 years), more likely hypertensive (60.6% vs. 55.5%) and diabetic (18.3% vs. 16.5%), and had higher CHA2 DS2 -VASc scores (3.0 ± 1.8 vs. 1.4 ± 1.4) (p < .0001 for all comparisons). The rates of all six complications were significantly higher in women. However, despite statistically significant differences, the overall incidences of major complications were very low in both sexes: stroke/TIA (women 0.51% vs. men 0.39%) and procedural mortality (women 0.25% vs. men 0.19%). CONCLUSION: Women experience significantly higher rates of AFCA complications. However, the incidence of major procedural complications is very low in both sexes. The higher rate of complications in women may be partially attributable to older age and a higher prevalence of comorbidities at the time of ablation. More detailed studies are needed to better define the mechanisms of increased risk in women and to identify strategies for closing the sex gap.

Global, Regional, and National Burden of Calcific Aortic Valve and Degenerative Mitral Valve Diseases, 1990-2017.

BACKGROUND: Nonrheumatic valvular diseases are common; however, no studies have estimated their global or national burden. As part of the Global Burden of Disease Study 2017, mortality, prevalence, and disability-adjusted life-years (DALYs) for calcific aortic valve disease (CAVD), degenerative mitral valve disease, and other nonrheumatic valvular diseases were estimated for 195 countries and territories from 1990 to 2017. METHODS: Vital registration data, epidemiologic survey data, and administrative hospital data were used to estimate disease burden using the Global Burden of Disease Study modeling framework, which ensures comparability across locations. Geospatial statistical methods were used to estimate disease for all countries, because data on nonrheumatic valvular diseases are extremely limited for some regions of the world, such as Sub-Saharan Africa and South Asia. Results accounted for estimated level of disease severity as well as the estimated availability of valve repair or replacement procedures. DALYs and other measures of health-related burden were generated for both sexes and each 5-year age group, location, and year from 1990 to 2017. RESULTS: Globally, CAVD and degenerative mitral valve disease caused 102 700 (95% uncertainty interval [UI], 82 700-107 900) and 35 700 (95% UI, 30 500-42 500) deaths, and 12.6 million (95% UI, 11.4 million-13.8 million) and 18.1 million (95% UI, 17.6 million-18.6 million) prevalent cases existed in 2017, respectively. A total of 2.5 million (95% UI, 2.3 million-2.8 million) DALYs were estimated as caused by nonrheumatic valvular diseases globally, representing 0.10% (95% UI, 0.09%-0.11%) of total lost health from all diseases in 2017. The number of DALYs increased for CAVD and degenerative mitral valve disease between 1990 and 2017 by 101% (95% UI, 79%-117%) and 35% (95% UI, 23%-47%), respectively. There is significant geographic variation in the prevalence, mortality rate, and overall burden of these diseases, with highest age-standardized DALY rates of CAVD estimated for high-income countries. CONCLUSIONS: These global and national estimates demonstrate that CAVD and degenerative mitral valve disease are important causes of disease burden among older adults. Efforts to clarify modifiable risk factors and improve access to valve interventions are necessary if progress is to be made toward reducing, and eventually eliminating, the burden of these highly treatable diseases.

Pro-Angiogenic Actions of CMC-Derived Extracellular Vesicles Rely on Selective Packaging of Angiopoietin 1 and 2, but Not FGF-2 and VEGF.

While the fundamental mechanism by which cardiac cell therapy mitigates ventricular dysfunction in the post ischemic heart remains poorly defined, donor cell paracrine signaling is presumed to be a chief contributor to the afforded benefits. Of the many bioactive molecules secreted by transplanted cells, extracellular vesicles (EVs) and their proteinaceous, nucleic acid, and lipid rich contents, comprise a heterogeneous assortment of prospective cardiotrophic factors-whose involvement in the activation of endogenous cardiac repair mechanism(s), including reducing fibrosis and promoting angiogenesis, have yet to be fully explained. In the current study we aimed to interrogate potential mechanisms by which cardiac mesenchymal stromal cell (CMC)-derived EVs contribute to the CMC pro-angiogenic paracrine signaling capacity in vitro. Vesicular transmission and biological activity of human CMC-derived EVs was evaluated in in vitro assays for human umbilical vein endothelial cell (HUVEC) function, including EV uptake, cell survival, migration, tube formation, and intracellular pathway activation. HUVECs incubated with EVs exhibited augmented cell migration, tube formation, and survival under peroxide exposure; findings which paralleled enhanced activation of the archetypal pro-survival/pro-angiogenic pathways, STAT3 and PI3K-AKT. Cytokine array analyses revealed preferential enrichment of a subset of prototypical angiogenic factors, Ang-1 and Ang-2, in CMC EVs. Interestingly, pharmacologic inhibition of Tie2 in HUVECs, the cognate receptors of angiopoietins, efficiently attenuated CMC-EV-induced HUVEC migration. Further, in additional assays a Tie2 kinase inhibitor exhibited specificity to inhibit Ang-1-, but not Ang-2-, induced HUVEC migration. Overall, these findings suggest that the pro-angiogenic activities of CMC EVs are principally mediated by Ang-1-Tie2 signaling.

Percutaneous left ventricular assist device support during ablation of ventricular tachycardia: A meta-analysis of current evidence.

INTRODUCTION: Catheter ablation of ventricular tachycardia (VT) can be an effective therapy to reduce VT burden, but often it is limited by the potential for hemodynamic instability. Percutaneous left ventricular assist devices (pLVADs) have been used to maintain hemodynamic support during VT ablation but the evidence regarding its clinical impact has been inconclusive. METHODS AND RESULTS: We sought to assess the clinical impact of pLVAD when used in VT ablation by conducting a meta-analysis of the current evidence. We searched Pubmed and found nine observational studies that compared clinical outcomes of VT ablation in patients with pLVAD support to controls with no pLVAD support. The pooled data did not show a significant difference in mortality between both groups, nor a difference in acute procedural success or in recurrence of VT. There was also no difference in the number of patients receiving a cardiac transplant or being enrolled in the transplant list. Although there was no difference in the ablation time between the groups, patients in the pLVAD group had a longer total procedural time and more procedure-related adverse effects. CONCLUSION: This meta-analysis did not show clinical benefits from using pLVAD support during VT ablation, whereas it was associated with longer procedure times and more complications. This study was, however, limited by the observational nature of the data. In view of these data, the risk and benefit of pLVAD support during VT ablation should be considered on an individual basis.

Exit sites on the epicardium rarely subtend critical diastolic path of ischemic VT on the endocardium: Implications for noninvasive ablation.

BACKGROUND: Noninvasive electrocardiographic mapping of ventricular tachycardia (VT) and ablation using stereotactic radiotherapy was recently reported. This strategy does not directly evaluate the critical diastolic components and assumes that the epicardial exit site of VT subtends closely over the endocardial mid-diastolic isthmus. OBJECTIVE: To determine if the epicardial exit site of VT spatially corresponds to the critical diastolic components of ischemic scar-related VT. MATERIALS AND METHODS: Intraoperative simultaneous endocardial and epicardial mapping were performed during VT using a 112-bipole endocardial balloon and 112-bipole epicardial sock array. In eight patients, nine VTs having entire diastolic circuit mapped were included in the study. The diastolic path and VT-exit sites (epicardial and endocardial) were determined. RESULTS: The diastolic path was mapped in the endocardium for all nine VTs (median length, 50; interquartile range [IQR], 28 mm). The tachycardia cycle length ranged from 210-500 ms. The VT-exit site was early in the endocardium for six VTs and on the epicardium for three VTs. The mid-diastolic isthmus and endocardial exit site of the six endocardial VTs were spatially distant from their epicardial exit site by a median distance of 32 and 27 mm, respectively. For the three VTs with an early epicardial exit, the isthmus and endocardial exit sites were distant from the epicardial exit site by a median distance of 34 and 38 mm, respectively. CONCLUSION: The epicardial exit site and the mid-diastolic isthmus sites were spatially distant and discrepant. Surface electrocardiography (ECG)-derived strategy in identifying epicardial exit site to select noninvasive ablation targets is prone to identify epicardial exit sites and may not identify critical targets in ischemic scar VT.

Oxygen Administration Does Not Influence the Prognosis of Acute Myocardial Infarction: A Meta-Analysis.

BACKGROUND: The safety and efficacy of supplemental oxygen in acute myocardial infarction (AMI) remains unclear. STUDY QUESTION: To evaluate the safety and efficacy of supplemental oxygen in patients who present with AMI. DATA SOURCES: We systematically searched PubMed, Embase, Cochrane Central Register of Controlled Trials, ISI Web of Science, Scopus, and conference proceedings from inception through January 2016. STUDY DESIGN: Eligible studies were randomized trials that evaluated the role of oxygen compared with room air in AMI. The clinical outcome measured was 30-day mortality, and odds ratio (OR) was calculated for the measured outcome. The Mantel-Haenszel method was used to pool 30-day mortality in a random-effects model. Sensitivity analysis was carried out to evaluate the effect of revascularization of the culprit artery on the outcome. RESULTS: The pooled analysis suggested no difference in 30-day mortality [OR 1.09; 95% confidence interval (CI), 0.30-4.00; P = 0.89] between oxygen and room air. Metaregression demonstrated that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). A subgroup analysis suggested a trend toward increased mortality with oxygen (OR 3.26; 95% CI, 0.94-11.29; P = 0.06) when less than half of the patient population underwent revascularization. On the other hand, there was a nonsignificant numerical decrease in mortality with oxygen (OR 0.41; 95% CI, 0.14-1.19; P = 0.10) in the presence of coronary revascularization. Metaregression confirmed that all the between-study variance was because of coronary revascularization (P = 0.01, R = 1.0). CONCLUSIONS: In this meta-analysis, we found that the evidence on the safety and efficacy of oxygen was not only weak and inconsistent but also had modest statistical power. The variation in results was mainly because of the presence or absence of revascularization of the culprit artery. Adequately powered studies are needed to further delineate the role of oxygen in patients undergoing coronary revascularization.

The Burden of Cardiovascular Diseases Among US States, 1990-2016.

Importance: Cardiovascular disease (CVD) is the leading cause of death in the United States, but regional variation within the United States is large. Comparable and consistent state-level measures of total CVD burden and risk factors have not been produced previously. Objective: To quantify and describe levels and trends of lost health due to CVD within the United States from 1990 to 2016 as well as risk factors driving these changes. Design, Setting, and Participants: Using the Global Burden of Disease methodology, cardiovascular disease mortality, nonfatal health outcomes, and associated risk factors were analyzed by age group, sex, and year from 1990 to 2016 for all residents in the United States using standardized approaches for data processing and statistical modeling. Burden of disease was estimated for 10 groupings of CVD, and comparative risk analysis was performed. Data were analyzed from August 2016 to July 2017. Exposures: Residing in the United States. Main Outcomes and Measures: Cardiovascular disease disability-adjusted life-years (DALYs). Results: Between 1990 and 2016, age-standardized CVD DALYs for all states decreased. Several states had large rises in their relative rank ordering for total CVD DALYs among states, including Arkansas, Oklahoma, Alabama, Kentucky, Missouri, Indiana, Kansas, Alaska, and Iowa. The rate of decline varied widely across states, and CVD burden increased for a small number of states in the most recent years. Cardiovascular disease DALYs remained twice as large among men compared with women. Ischemic heart disease was the leading cause of CVD DALYs in all states, but the second most common varied by state. Trends were driven by 12 groups of risk factors, with the largest attributable CVD burden due to dietary risk exposures followed by high systolic blood pressure, high body mass index, high total cholesterol level, high fasting plasma glucose level, tobacco smoking, and low levels of physical activity. Increases in risk-deleted CVD DALY rates between 2006 and 2016 in 16 states suggest additional unmeasured risks beyond these traditional factors. Conclusions and Relevance: Large disparities in total burden of CVD persist between US states despite marked improvements in CVD burden. Differences in CVD burden are largely attributable to modifiable risk exposures.

Identification and Ablation of Dormant Conduction in Atrial Fibrillation Using Adenosine.

BACKGROUND: Ablation is used for treatment of atrial fibrillation (AF) but recurrence is common. Dormant conduction is hypothesized to be responsible for these recurrences, and the role of adenosine in identification and ablation of these pathways is controversial with conflicting results on AF recurrence. MATERIALS AND METHODS: We conducted a meta-analysis for studies evaluating AF ablation and adenosine use. Included in the meta-analysis were human studies that compared ablation using adenosine or adenosine triphosphate (ATP) and reported freedom from AF in patients beyond a minimum follow-up of 6 months. RESULTS: Our analysis suggests that the use of adenosine leads to a decrease in recurrence of AF compared to the cohort which did not utilize adenosine. Subgroup analysis showed no difference in the recurrence of AF with the modality used for ablation (cryoablation vs. radiofrequency ablation) or with the preparation of adenosine used (ATP vs. adenosine). There was a significant benefit in delayed administration of ATP over early administration. Pooling results of only randomized control trials did not show any significant difference in AF recurrence. CONCLUSIONS: Adenosine-guided identification and ablation of dormant pathways may lead to a decrease in recurrence of AF.

The effect of left ventricular pacing on transmural activation delay in myopathic human hearts.

Aims: Left ventricular (LV) epicardial pacing (LVEpiP) in human myopathic hearts does not decrease global epicardial activation delay compared with right ventricular (RV) endocardial pacing (RVEndoP); however, the effect on transmural activation delay has not been evaluated. To characterize the transmural electrical activation delay in human myopathic hearts during RVEndoP and LVEpiP compared with global epicardial activation delay. Methods and results: Explanted hearts from seven patients (5 male, 46 ± 10 years) undergoing cardiac transplantation were Langendorff-perfused and mapped using an epicardial sock electrode array (112 electrodes) and 25 transmural plunge needles (four electrodes, 2 mm spacing), for a total of 100 unipolar transmural electrodes. Electrograms were recorded during LVEpiP and RVEndoP, and epicardial (sock) and transmural (needle) activation times, along with patterns of activation, were compared. There was no difference between the global epicardial activation times (LVEpiP 147 ± 8 ms vs. RVEndoP 156 ± 17 ms, P = 0.46). The mean LV transmural activation time during LVEpiP was significantly shorter than that during RVEndoP (125 ± 44 vs. 172 ± 43 ms, P < 0.001). During LVEpiP, of the transmural layers endo-, mid-myocardium and epicardium, LV endocardial layer was often the earliest compared with other transmural layers. Conclusion: In myopathic human hearts, LVEpiP did not decrease global epicardial activation delays compared with RVEndoP. LV epicardial pacing led to early activation of the LV endocardium, revealing the importance of the LV endocardium even when pacing from the LV epicardium.

Stent thrombosis with bioabsorbable polymer drug-eluting stents: insights from the Food and Drug Administration database.

BACKGROUND: SYNERGY, a bioabsorbable polymer-based, everolimus-eluting stent (BP-DES), recently received regulatory approval in the USA for use in percutaneous coronary interventions. Yet, information on the safety of BP-DES in routine clinical practice is limited. Our aim was to compare the safety of the recently approved BP-DES with current durable polymer drug-eluting stents (DP-DES) by analyzing adverse events, namely, stent thrombosis (ST), reported to the Manufacturer and User Facility Device Experience (MAUDE) database. MATERIALS AND METHODS: The MAUDE database requires nationwide mandatory notification for adverse events on devices approved for clinical use. This database was searched for adverse events reported between 1 October 2015 and 25 December 2016, encountered after the placement of either BP-DES or DP-DES. Only those adverse events were included where the exposure period to the stents was comparable after the index procedure. Of all the adverse events reported, the event of interest was ST. RESULTS: A total of 951 adverse events were reported. ST occurred in 48/951 of all events, 31/309 and 17/642 when BP-DES or DP-DES were used, respectively (P=0.00001). Of the 31 ST events with BP-DES, 68% (21/31) occurred within less than or equal to 24 h of the index procedure and 52% (16/31) occurred within less than or equal to 2 h. CONCLUSION: Our results raise the possibility of an increased risk of ST, particularly early ST (within 24 h), with the recently approved BP-DES. However, because of the inherent limitations of reporting within the MAUDE database, these data merely highlight a potential need for additional surveillance and randomized trials to assess further the safety of the bioabsorbable platform.

Stability of pacing indices and need for pacing in cardiac transplant patients over 1 year of follow-up.

BACKGROUND: A significant minority of cardiac transplant patients require permanent pacemaker (PPM) implant, primarily for sinus node dysfunction. The stability of pacing indices has not been determined in this unique patient population, and data regarding ongoing need for pacing are limited. METHODS: Pacing indices (sensing, threshold, and impedance) as well as the percentage of time patients required pacing were recorded, from 30 cardiac transplant patients that underwent PPM implant, over 1 year of follow-up. Repeated measure ANOVA (analysis of variance) was used to compare pacing indices and the percentage of time patients required pacing in each cardiac chamber (right atrium (RA) and right ventricle (RV)) and at different time points. RESULTS: There was no difference in sensing among the follow-up time points (p = 0.9). Thresholds at 3 months were significantly higher compared to the day of implant (p = 0.005) and the day after implant (p = 0.03). Impedances at implant were significantly higher compared to day 1 (p < 0.001), 3 months (p < 0.003), and 12 months (p < 0.001) post-implant. The mean percentage of RA pacing was 85 ± 6% the day after implant, 74 ± 6% at 3 months, and 80 ± 6% at 1 year (p = 0.17). CONCLUSION: In cardiac transplant patients, pacing impedances decrease and thresholds trend up in short-term follow-up, but subsequent sensing, threshold, and impedance remain stable at 1 year. This is comparable to the pattern observed among noncardiac transplant PPM recipients. The atrial pacing percentage was stable over 1 year, suggesting continued relative sinus node dysfunction.

Increased Risk of Adverse Neurocognitive Outcomes With Proprotein Convertase Subtilisin-Kexin Type 9 Inhibitors.

BACKGROUND: There is encouraging evidence of the efficacy of proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors; however, their long-term safety remains unclear. We performed a meta-analysis of studies to evaluate the long-term safety of PCSK9 inhibitors. METHODS AND RESULTS: Our search strategy yielded 11 studies (9 smaller early-phase and 2 larger outcome trials). The outcomes assessed were cumulative serious adverse events, musculoskeletal adverse events, neurocognitive adverse events, and stroke. Odds ratio (OR) was calculated using the Mantel-Haenszel method. Subgroup analysis was done to assess the difference in safety between the smaller early-phase studies and the larger outcome studies. Our meta-analysis suggested no difference in the incidence of serious adverse events (OR, 1.00; 95% confidence interval [CI], 0.88-1.15), musculoskeletal adverse events (OR, 1.01; 95% CI, 0.87-1.13), neurocognitive adverse events (OR, 1.29; 95% CI, 0.64-2.59), or stroke (OR, 1.44; 95% CI, 0.57-3.65) with the use of PCSK9 inhibitors. Subgroup analysis of the 2 large outcome studies did suggest an increased incidence of neurocognitive adverse events (OR, 2.85; 95% CI, 1.34-6.06) with the use of PCSK9 inhibitors. However, the overall incidence of neurocognitive adverse events and stroke was <1%, whereas the cumulative incidence of serious adverse events and musculoskeletal events was >10% in both the groups. CONCLUSIONS: Our analysis suggests that PCSK9 inhibitors are not associated with an increased risk of cumulative severe adverse effects, musculoskeletal effects, or stroke. There is a signal toward adverse neurocognitive effects, seen in the outcome studies with a larger sample size and longer follow-up. There should be close monitoring, for the increased risk of neurocognitive events in the ongoing outcome studies and post-marketing surveillance.

Burden of Diarrhea in the Eastern Mediterranean Region, 1990-2013: Findings from the Global Burden of Disease Study 2013.

Diarrheal diseases (DD) are leading causes of disease burden, death, and disability, especially in children in low-income settings. DD can also impact a child's potential livelihood through stunted physical growth, cognitive impairment, and other sequelae. As part of the Global Burden of Disease Study, we estimated DD burden, and the burden attributable to specific risk factors and particular etiologies, in the Eastern Mediterranean Region (EMR) between 1990 and 2013. For both sexes and all ages, we calculated disability-adjusted life years (DALYs), which are the sum of years of life lost and years lived with disability. We estimate that over 125,000 deaths (3.6% of total deaths) were due to DD in the EMR in 2013, with a greater burden of DD in low- and middle-income countries. Diarrhea deaths per 100,000 children under 5 years of age ranged from one (95% uncertainty interval [UI] = 0-1) in Bahrain and Oman to 471 (95% UI = 245-763) in Somalia. The pattern for diarrhea DALYs among those under 5 years of age closely followed that for diarrheal deaths. DALYs per 100,000 ranged from 739 (95% UI = 520-989) in Syria to 40,869 (95% UI = 21,540-65,823) in Somalia. Our results highlighted a highly inequitable burden of DD in EMR, mainly driven by the lack of access to proper resources such as water and sanitation. Our findings will guide preventive and treatment interventions which are based on evidence and which follow the ultimate goal of reducing the DD burden.

Impact of Cell Therapy on Myocardial Perfusion and Cardiovascular Outcomes in Patients With Angina Refractory to Medical Therapy: A Systematic Review and Meta-Analysis.

RATIONALE: The effect of stem/progenitor cells on myocardial perfusion and clinical outcomes in patients with refractory angina remains unclear because studies published to date have been small phase I-II trials. OBJECTIVE: We performed a meta-analysis of randomized controlled trials to evaluate the effect of cell-based therapy in patients with refractory angina who were ineligible for coronary revascularization. METHODS AND RESULTS: Several data sources were searched from inception to September 2015, which yielded 6 studies. The outcomes pooled were indices of angina (anginal episodes, Canadian Cardiovascular Society angina class, exercise tolerance, and antianginal medications), myocardial perfusion, and clinical end points. We combined the reported clinical outcomes (myocardial infarction, cardiac-related hospitalization, and mortality) into a composite end point (major adverse cardiac events). Mean difference (MD), standardized mean differences, or odds ratio were calculated to assess relevant outcomes. Our analysis shows an improvement in anginal episodes (MD, -7.81; 95% confidence interval [CI], -15.22 to -0.41), use of antianginal medications (standardized MD, -0.59; 95% CI, -1.03 to -0.14), Canadian Cardiovascular Society class (MD, -0.58; 95% CI, -1.00 to -0.16), exercise tolerance (standardized MD, 0.331; 95% CI, 0.08 to 0.55), and myocardial perfusion (standardized MD, -0.49; 95% CI, -0.76 to -0.21) and a decreased risk of major adverse cardiac events (odds ratio, 0.49; 95% CI, 0.25 to 0.98) and arrhythmias (odds ratio, 0.25; 95% CI, 0.06 to 0.98) in cell-treated patients when compared with patients on maximal medical therapy. CONCLUSIONS: The present meta-analysis indicates that cell-based therapies are not only safe but also lead to an improvement in indices of angina, relevant clinical outcomes, and myocardial perfusion in patients with refractory angina. These encouraging results suggest that larger, phase III randomized controlled trials are in order to conclusively determine the effect of stem/progenitor cells in refractory angina.

Feeding the fibrillating heart: Dichloroacetate improves cardiac contractile dysfunction following VF.

Ventricular fibrillation (VF) is an important cause of sudden cardiac arrest following myocardial infarction. Following resuscitation from VF, decreased cardiac contractile function is a common problem. During and following myocardial ischemia, decreased glucose oxidation, increased anaerobic glycolysis for cardiac energy production are harmful and energetically expensive. The objective of the present study is to determine the effects of dichloroacetate (DCA), a glucose oxidation stimulator, on cardiac contractile dysfunction following ischemia-induced VF. Male Sprague-Dawley rat hearts were Langendorff perfused in Tyrode's buffer. Once stabilized, hearts were subjected to 15 min of global ischemia and 5 min of aerobic reperfusion in the presence or absence of DCA. At the 6th min of reperfusion, VF was induced electrically, and terminated. Left ventricular (LV) pressure was measured using a balloon. Pretreatment with DCA significantly improved post-VF left ventricular developed pressure (LVDP) and dp/dtmax. In DCA-pretreated hearts, post-VF lactate production and pyruvate dehydrogenase (PDH) phosphorylation were significantly reduced, indicative of stimulated glucose oxidation, and inhibited anaerobic glycolysis by activation of PDH. Epicardial NADH fluorescence was increased during global ischemia above preischemic levels, but decreased below preischemia levels following VF, with no differences between nontreated controls and DCA-pretreated hearts, whereas DCA pretreatment increased NADH production in nonischemic hearts. With exogenous fatty acids (FA) added to the perfusion solution, DCA pretreatment also resulted in improvements in post-VF LVDP and dp/dtmax, indicating that the presence of exogenous FA did not affect the beneficial actions of DCA. In conclusion, enhancement of PDH activation by DCA mitigates cardiac contractile dysfunction following ischemia-induced VF.

Tracking rotors with minimal electrodes: modulation index-based strategy.

BACKGROUND: High-frequency periodic sources during cardiac fibrillation can be detected by phase mapping techniques. To enable practical therapeutic options for modulating periodic sources (existing techniques require high density multielectrode arrays and real time simultaneous mapping capability), a method to identify electrogram morphologies colocalizing to rotors that can be implemented on few electrograms needs to be devised. METHOD AND RESULTS: Multichannel ventricular fibrillation electrogram data from 7 isolated human hearts using Langendorff setup and intraoperative clinical data from 2 human hearts were included in the analysis. The spatial locations of rotors were identified using phase maps constructed from 112 electrograms. Electrograms were analyzed for repeating patterns and discriminating signal morphologies around the locations of rotors and nonrotors were identified and quantified. Features were extracted from the unipolar electrogram patterns, which corroborated well with the spatial location of rotors. The results suggest that using the proposed modulation index feature, and as low as 1 sample point in the vicinity of the rotors, an accuracy as high as 86% (P<0.001) was obtained in separating rotor locations versus nonrotor locations. The analysis of bipolar electrogram signatures in the vicinity of the rotor locations suggest that 62.5% of the rotors occur at locations where the bipolar electrogram demonstrates continuous activities during ventricular fibrillation. CONCLUSIONS: Unipolar electrogram extracted modulation index-based detection of rotors is feasible with few electrodes and has greater detection rate than bipolar approach. This strategy may be suitable for nonarray-based single mapping catheter enabled detection of rotors.