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1.
Circulation ; 141(21): 1670-1680, 2020 05 26.
Article in English | MEDLINE | ID: mdl-32223336

ABSTRACT

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.


Subject(s)
Aortic Valve Insufficiency/epidemiology , Aortic Valve Stenosis/epidemiology , Aortic Valve/pathology , Calcinosis/epidemiology , Global Health , Mitral Valve Insufficiency/epidemiology , Mitral Valve Prolapse/epidemiology , Age Distribution , Aortic Valve/diagnostic imaging , Aortic Valve/surgery , Aortic Valve Insufficiency/diagnostic imaging , Aortic Valve Insufficiency/mortality , Aortic Valve Insufficiency/surgery , Aortic Valve Stenosis/diagnostic imaging , Aortic Valve Stenosis/mortality , Aortic Valve Stenosis/surgery , Calcinosis/diagnostic imaging , Calcinosis/mortality , Calcinosis/surgery , Cost of Illness , Female , Health Status Disparities , Healthcare Disparities , Humans , Male , Mitral Valve Insufficiency/diagnostic imaging , Mitral Valve Insufficiency/mortality , Mitral Valve Insufficiency/surgery , Mitral Valve Prolapse/diagnostic imaging , Mitral Valve Prolapse/mortality , Mitral Valve Prolapse/surgery , Prevalence , Quality of Life , Risk Assessment , Risk Factors , Time Factors
2.
Am J Ther ; 26(1): e151-e160, 2019.
Article in English | MEDLINE | ID: mdl-27846023

ABSTRACT

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.


Subject(s)
Myocardial Infarction/therapy , Oxygen Inhalation Therapy , Oxygen/administration & dosage , Humans , Myocardial Infarction/mortality , Odds Ratio , Prognosis , Randomized Controlled Trials as Topic , Survival Analysis , Treatment Outcome
4.
Coron Artery Dis ; 28(7): 564-569, 2017 Nov.
Article in English | MEDLINE | ID: mdl-28731889

ABSTRACT

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.


Subject(s)
Absorbable Implants , Coronary Thrombosis/etiology , Drug-Eluting Stents , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/instrumentation , United States Food and Drug Administration , Cardiovascular Agents/administration & dosage , Coronary Thrombosis/diagnostic imaging , Databases, Factual , Everolimus/administration & dosage , Humans , Prosthesis Design , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United States
5.
J Interv Card Electrophysiol ; 49(1): 27-32, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28181107

ABSTRACT

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.


Subject(s)
Arrhythmia, Sinus/diagnosis , Arrhythmia, Sinus/etiology , Cardiac Pacing, Artificial/methods , Electrocardiography/methods , Heart Transplantation/adverse effects , Needs Assessment , Arrhythmia, Sinus/prevention & control , Female , Follow-Up Studies , Humans , Male , Middle Aged , Reproducibility of Results , Retrospective Studies , Sensitivity and Specificity , Treatment Outcome
6.
Article in English | MEDLINE | ID: mdl-28073851

ABSTRACT

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.


Subject(s)
Cognition Disorders/chemically induced , Cognition/drug effects , Dyslipidemias/drug therapy , Hypolipidemic Agents/adverse effects , Lipids/blood , PCSK9 Inhibitors , Serine Proteinase Inhibitors/adverse effects , Stroke/chemically induced , Adolescent , Adult , Aged , Biomarkers/blood , Chi-Square Distribution , Clinical Trials as Topic , Cognition Disorders/diagnosis , Cognition Disorders/epidemiology , Cognition Disorders/psychology , Dyslipidemias/blood , Dyslipidemias/diagnosis , Dyslipidemias/enzymology , Female , Humans , Incidence , Male , Middle Aged , Odds Ratio , Proprotein Convertase 9/metabolism , Risk Assessment , Risk Factors , Stroke/diagnosis , Stroke/epidemiology , Stroke/physiopathology , Treatment Outcome , Young Adult
7.
Circ Res ; 118(6): 984-93, 2016 Mar 18.
Article in English | MEDLINE | ID: mdl-26838794

ABSTRACT

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.


Subject(s)
Angina Pectoris/physiopathology , Angina Pectoris/therapy , Cell- and Tissue-Based Therapy/methods , Percutaneous Coronary Intervention/methods , Angina Pectoris/diagnosis , Cardiovascular Agents/pharmacology , Cardiovascular Agents/therapeutic use , Exercise Tolerance/drug effects , Exercise Tolerance/physiology , Humans , Randomized Controlled Trials as Topic/methods , Treatment Outcome
8.
J Cardiovasc Electrophysiol ; 24(7): 813-21, 2013 Jul.
Article in English | MEDLINE | ID: mdl-23647964

ABSTRACT

INTRODUCTION: Transplantation of mesenchymal stem cells (MSCs) has shown therapeutic potential for cardiovascular diseases, but the electrophysiological implications are not understood. The purpose of this study was to evaluate the impact of MSC transplantation on adverse electrophysiological remodeling in the heart following myocardial infarction (MI). METHODS AND RESULTS: Three weeks after coronary ligation to induce MI in rats, MSCs or culture medium were directly injected into each infarct. One to two weeks later, hearts were excised, Langendorff-perfused, and optically mapped using the potentiometric fluorescent dye Di-4-ANEPPS. Quantitative real-time PCR was also performed to assess gene expression. Optical mapping showed that post-MI reduction in conduction velocity (from 0.70 ± 0.04 m/s in 12 normal controls to 0.47 ± 0.02 m/s in 11 infarcted hearts, P < 0.05) was attenuated with MSC transplantation (0.65 ± 0.04 m/s, n = 18, P < 0.05). Electrophysiological changes correlated with higher vascular density and better-preserved ventricular geometry in MSC-transplanted hearts. A number of ion channel genes showed changes in RNA expression following infarction. In particular, the expression of Kir2.1, which mediates the inward rectifier potassium current, I(K1), was reduced in infarcted tissues (n = 7) to 13.8 ± 3.7% of normal controls, and this post-MI reduction was attenuated with MSC transplantation (44.4 ± 11.2%, n = 7, P < 0.05). CONCLUSION: In addition to promoting angiogenesis and limiting adverse structural remodeling in infarcted hearts, MSC transplantation also alters ion channel expression and mitigates electrophysiological remodeling. Further understanding of the electrophysiological impact of MSC transplantation to the heart may lead to the development of cell-based therapies for post-MI arrhythmias.


Subject(s)
Mesenchymal Stem Cell Transplantation , Myocardial Infarction/surgery , Ventricular Remodeling , Animals , Disease Models, Animal , Electrophysiological Phenomena , Female , Male , Rats , Rats, Inbred Lew , Ventricular Remodeling/physiology
9.
Circ Res ; 109(11): 1309-18, 2011 Nov 11.
Article in English | MEDLINE | ID: mdl-21980123

ABSTRACT

RATIONALE: Ventricular fibrillation (VF) leads to global ischemia. The modulation of ischemia-dependent pathways may alter the electrophysiological evolution of VF. OBJECTIVE: We addressed the hypotheses that there is regional disease-related expression of K(ATP) channels in human cardiomyopathic hearts and that K(ATP) channel blockade promotes spontaneous VF termination by attenuating spatiotemporal dispersion of refractoriness. METHODS AND RESULTS: In a human Langendorff model, electric mapping of 6 control and 9 treatment (10 µmol/L glibenclamide) isolated cardiomyopathic hearts was performed. Spontaneous defibrillation was studied and mean VF cycle length was compared regionally at VF onset and after 180 seconds between control and treatment groups. K(ATP) subunit gene expression was compared between LV endocardium versus epicardium in myopathic hearts. Spontaneous VF termination occurred in 1 of 6 control hearts and 7 of 8 glibenclamide-treated hearts (P=0.026). After 180 seconds of ischemia, a transmural dispersion in VF cycle length was observed between epicardium and endocardium (P=0.001), which was attenuated by glibenclamide. There was greater gene expression of all K(ATP) subunit on the endocardium compared with the epicardium (P<0.02). In an ischemic rat heart model, transmural dispersion of refractoriness (ΔERP(Transmural)=ERP(Epicardium)-ERP(Endocardium)) was verified with pacing protocols. ΔERP(Transmural) in control was 5 ± 2 ms and increased to 36 ± 5 ms with ischemia. This effect was greatly attenuated by glibenclamide (ΔERP(Transmural) for glibenclamide+ischemia=4.9 ± 4 ms, P=0.019 versus control ischemia). CONCLUSIONS: K(ATP) channel subunit gene expression is heterogeneously altered in the cardiomyopathic human heart. Blockade of K(ATP) channels promotes spontaneous defibrillation in cardiomyopathic human hearts by attenuating the ischemia-dependent spatiotemporal heterogeneity of refractoriness during early VF.


Subject(s)
Cardiomyopathy, Dilated/complications , KATP Channels/physiology , Ventricular Fibrillation/physiopathology , Action Potentials/drug effects , Animals , Endocardium/metabolism , Glyburide/pharmacology , Humans , In Vitro Techniques , Lidocaine/pharmacology , Male , Myocardial Ischemia/etiology , Pacemaker, Artificial , Perfusion , Pericardium/metabolism , RNA, Messenger/biosynthesis , Rats , Rats, Sprague-Dawley , Refractory Period, Electrophysiological/drug effects , Ventricular Fibrillation/etiology
10.
Article in English | MEDLINE | ID: mdl-19963772

ABSTRACT

The aim of this study is to determine if some of the characteristics of reconstructed unipolar electrograms from the noncontact mapping system can be used to detect epicardial electrical activation in a canine heart. This would help the electrophysiologist know where exactly the origin or the critical point in tissue is located. Following this, arrhythmia can be successfully treated by ablating that part of the tissue of heart. Virtual electrograms were recorded while pacing the right ventricle of an open-chest dog at multiple endocardial and epicardial sites using the commercially available noncontact mapping system (EnSite 3000). The endocardial and epicardial paced virtual electrograms from the juxtaposing sites allow for analyzing systematically the differences in their morphologies. Maximal dV/dt, area under the depolarization curve and latency extracted from unipolar electrograms demonstrated significant difference between epicardial and endocardial pacing sites with a p-value of less than 0.01 in all three cases. The above features were fed to a linear discriminant analysis based classifier and high classification accuracy was achieved. In conclusion, reliable criteria can be proposed to allow for discrimination of an endocardial versus epicardial origin of electrical activation.


Subject(s)
Arrhythmias, Cardiac/physiopathology , Electrocardiography/methods , Epicardial Mapping/methods , Animals , Arrhythmias, Cardiac/diagnosis , Body Surface Potential Mapping/methods , Dogs , Endocardium/physiology , ROC Curve , User-Computer Interface
11.
Circ Arrhythm Electrophysiol ; 2(5): 562-70, 2009 Oct.
Article in English | MEDLINE | ID: mdl-19843925

ABSTRACT

BACKGROUND: Action potential duration (APD) variation is an important determinant of wave break and reentry. The determinants of APD variability during early ventricular fibrillation (VF) in myopathic human hearts have not been studied. The objective of this study was to study the role of APD restitution and short-term cardiac memory on variation in human VF. METHODS AND RESULTS: The study consisted of 7 patients (67+/-9 years old) with ejection fraction <35%. Monophasic action potentials were recorded from the right and/or left ventricular septum during VF. APD(60/90) was measured in sinus beat preceding induction of VF, and its amplitude was used to define 60%/90% repolarization in VF. The monophasic action potential upstroke (dV/dt(max)) was used to characterize local excitability. Simple linear regression showed that variability in APD(n60) was determined by APD/diastolic interval restitution (R(2)=0.48, P<0.0001) and short-term memory (APD(60) n-1, n-2, n-3, n-4; R(2)=0.55, 0.40, 0.33, and 0.27 respectively; P<0.001). Using multiple stepwise regression, short-term memory and restitution accounted for 62% of variance in APD(60) (P<0.001). Individually, memory effect had the greatest contribution to APD variability (R(2)=0.55, P<0.0001). CONCLUSIONS: In early human VF, short-term memory and APD/diastolic interval restitution explain most of the APD variability, with memory effects predominating. This suggests that in early human VF, short-term cardiac memory may provide a novel therapeutic target to modulate progression of VF in myopathic patients.


Subject(s)
Action Potentials/physiology , Heart Conduction System/physiopathology , Ventricular Fibrillation/physiopathology , Aged , Aged, 80 and over , Cardiac Catheterization , Defibrillators, Implantable , Electrocardiography , Humans , Linear Models , Male , Middle Aged , Ventricular Fibrillation/prevention & control
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