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1.
Heart Rhythm ; 2024 Apr 07.
Article in English | MEDLINE | ID: mdl-38588995

ABSTRACT

BACKGROUND: The CONVERGE trial demonstrated that hybrid epicardial and endocardial ablation was more effective than catheter ablation for the treatment of persistent atrial fibrillation (AF) at 1 year. Long-term real-world outcome data are scarce. OBJECTIVE: We described a single-center experience by evaluating the long-term effectiveness and safety of hybrid epicardial-endocardial ablation. METHODS: This is a retrospective single-center study. Patients were followed up to 4 years. The primary end point was the rate of AF recurrence up to 4 years postablation. Secondary end points included reduction in antiarrhythmic therapy use, the effect of the ligament of Marshall removal, epicardial posterior wall, 3-dimensional mapping during epicardial ablation, and left atrial appendage exclusion as adjunct intraoperative interventions for AF recurrence. RESULTS: Of the 170 patients, 86.5% had persistent AF and 13.5% had long-standing persistent AF. AF-free survival was 87.6% at 1 year, 76.9% at 2 years, 70.4% at 3 years, and 59.3% at 4 years. Antiarrhythmic drug use was 87.6% at baseline and reduced to 21%, 20.6%, 18%, and 14.1% at year 1, 2, 3, and 4, respectively (P < .01 for all). Three-dimensional epicardial mapping showed a significant reduction in combined recurrence from 42% to 25% over 4 years of follow-up (P = .023). Ligament of Marshall and left atrial appendage exclusion showed numerical reduction in AF recurrence from 35% to 26% (P = .49) and from 44% to 30% (P = .07). CONCLUSION: The hybrid convergent procedure reduces AF recurrence and the need for antiarrhythmic drugs and, while maintaining a good safety profile, for the treatment of persistent and long-standing persistent AF.

2.
J Card Fail ; 29(4): 473-478, 2023 04.
Article in English | MEDLINE | ID: mdl-36195201

ABSTRACT

BACKGROUND: Cardiologists performing coronary angiography (CA) and percutaneous coronary intervention (PCI) are at risk of health problems related to chronic occupational radiation exposure. Unlike during CA and PCI, physician radiation exposure during right heart catheterization (RHC) and endomyocardial biopsy (EMB) has not been adequately studied. The objective of this study was to assess physicians' radiation doses during RHC with and without EMB and compare them to those of CA and PCI. METHODS: Procedural head-level physician radiation doses were collected by real-time dosimeters. Radiation-dose metrics (fluoroscopy time, air kerma [AK] and dose area product [DAP]), and physician-level radiation doses were compared among RHC, RHC with EMB, CA, and PCI. RESULTS: Included in the study were 351 cardiac catheterization procedures. Of these, 36 (10.3%) were RHC, 42 (12%) RHC with EMB, 156 (44.4%) CA, and 117 (33.3%) PCI. RHC with EMB and CA had similar fluoroscopy time. AK and DAP were progressively higher for RHC, RHC with EMB, CA, and PCI. Head-level physician radiation doses were similar for RHC with EMB vs CA (P = 0.07). When physicians' radiation doses were normalized to DAP, RHC and RHC with EMB had the highest doses. CONCLUSION: Physicians' head-level radiation doses during RHC with EMB were similar to those of CA. After normalizing to DAP, RHC and RHC with EMB were associated with significantly higher physician radiation doses than CA or PCI. These observations suggest that additional protective measures should be undertaken to decrease physicians' radiation exposure during RHC and, in particular, RHC with EMB.


Subject(s)
Heart Failure , Percutaneous Coronary Intervention , Physicians , Radiation Exposure , Humans , Percutaneous Coronary Intervention/adverse effects , Radiation Dosage , Radiation Exposure/adverse effects , Cardiac Catheterization/adverse effects , Cardiac Catheterization/methods , Biopsy/adverse effects , Coronary Angiography/adverse effects
3.
JAMA Netw Open ; 5(7): e2220597, 2022 07 01.
Article in English | MEDLINE | ID: mdl-35797046

ABSTRACT

Importance: Transesophageal echocardiography during percutaneous left atrial appendage closure (LAAO) and transcatheter edge-to-edge mitral valve repair (TEER) require an interventional echocardiographer to stand near the radiation source and patient, the primary source of scatter radiation. Despite previous work demonstrating high radiation exposure for interventional cardiologists performing percutaneous coronary and structural heart interventions, similar data for interventional echocardiographers are lacking. Objective: To assess whether interventional echocardiographers are exposed to greater radiation doses than interventional cardiologists and sonographers during structural heart procedures. Design, Setting, and Participants: In this single-center cross-sectional study, radiation doses were collected from interventional echocardiographers, interventional cardiologists, and sonographers at a quaternary care center during 30 sequential LAAO and 30 sequential TEER procedures from July 1, 2016, to January 31, 2018. Participants and study personnel were blinded to radiation doses through data analysis (January 1, 2020, to October 12, 2021). Exposures: Occupation defined as interventional echocardiographers, interventional cardiologists, and sonographers. Main Outcomes and Measures: Measured personal dose equivalents per case were recorded using real-time radiation dosimeters. Results: A total of 60 (30 TEER and 30 LAAO) procedures were performed in 60 patients (mean [SD] age, 79 [8] years; 32 [53.3%] male) with a high cardiovascular risk factor burden. The median radiation dose per case was higher for interventional echocardiographers (10.6 µSv; IQR, 4.2-22.4 µSv) than for interventional cardiologists (2.1 µSv; IQR, 0.2-8.3 µSv; P < .001). During TEER, interventional echocardiographers received a median radiation dose of 10.5 µSv (IQR, 3.1-20.5 µSv), which was higher than the median radiation dose received by interventional cardiologists (0.9 µSv; IQR, 0.1-12.2 µSv; P < .001). During LAAO procedures, the median radiation dose was 10.6 µSv (IQR, 5.8-24.1 µSv) among interventional echocardiographers and 3.5 (IQR, 1.3-6.3 µSv) among interventional cardiologists (P < .001). Compared with interventional echocardiographers, sonographers exhibited low median radiation doses during both LAAO (0.2 µSv; IQR, 0.0-1.6 µSv; P < .001) and TEER (0.0 µSv; IQR, 0.0-0.1 µSv; P < .001). Conclusions and Relevance: In this cross-sectional study, interventional echocardiographers were exposed to higher radiation doses than interventional cardiologists during LAAO and TEER procedures, whereas sonographers demonstrated comparatively lower radiation doses. Higher radiation doses indicate a previously underappreciated occupational risk faced by interventional echocardiographers, which has implications for the rapidly expanding structural heart team.


Subject(s)
Cardiologists , Occupational Exposure , Radiation Exposure , Aged , Cross-Sectional Studies , Female , Humans , Male , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control , Radiation Dosage
4.
Catheter Cardiovasc Interv ; 100(2): 207-213, 2022 08.
Article in English | MEDLINE | ID: mdl-35621166

ABSTRACT

OBJECTIVE: This study was performed to investigate the efficacy and safety of robotic diagnostic coronary angiography. BACKGROUND: Robotic percutaneous coronary intervention is associated with marked reductions in physician radiation exposure. Development of robotic diagnostic coronary angiography might similarly impact occupational safety. METHODS: Stable patients referred for coronary angiography were prospectively enrolled. After obtaining vascular access, diagnostic catheters were manually advanced over a wire to the ascending aorta. All subsequent catheter movements were performed robotically. The primary endpoint was procedural success, defined as robotic completion of coronary angiography without conversion to a manual procedure and the absence of procedural major adverse cardiovascular events (MACE-cardiac death, cardiac arrest, or stroke) and major angiographic complications (coronary/aortic dissection or embolization). The primary hypothesis was that the observed rate of the primary endpoint, evaluated at the completion of coronary angiography, would meet a pre-specified performance goal of 74.5%. RESULTS: Among 46 consecutive patients (age 67 ± 12 years; 69.6% male), diagnostic coronary angiography was completed robotically in all cases without the need for manual conversion and without any MACE or major angiographic complications. Thus, procedural success was 100%, which was significantly higher than the pre-specified performance goal (p < 0.001). Robotic coronary angiography was completed using 2 [2, 3] catheters per case with a median procedural time of 15 [11, 20] minutes. CONCLUSIONS: Robotic diagnostic coronary angiography was performed with 100% procedural success and no observed complications. These results support the performance of future studies to further explore robotic coronary angiography.


Subject(s)
Percutaneous Coronary Intervention , Robotics , Aged , Coronary Angiography/adverse effects , Female , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Percutaneous Coronary Intervention/methods , Stents , Treatment Outcome
5.
Am J Cardiol ; 169: 18-23, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35045930

ABSTRACT

Fewer ST-elevation myocardial infarctions (STEMIs) presentations and increased delays in care occurred during the COVID-19 pandemic in urban areas. Whether these associations occurred in a more rural population has not been previously reported. Our objective was to evaluate the impact of COVID-19 on time-to-presentation for STEMI in rural locations. Patients presenting to a large STEMI network spanning 27 facilities and 13 predominantly rural counties between January 1, 2016 and April 30, 2020 were included. Presentation delays, defined as time from symptom onset to arrival at the first medical facility, classified as ≥12 and ≥24 hours from symptom onset were compared among patients in the pre-COVID-19 and the early COVID-19 eras. To account for patient-level differences, 2:1 propensity score matching was performed using binary logistic regression. Among 1,286 patients with STEMI, 1,245 patients presented in the pre-COVID-19 era and 41 presented during the early COVID-19 era. Presentation delays ≥12 hours (19.5% vs 4.0%) and ≥24 hours (14.6% and 0.2%) were more common in COVID-19 than pre-COVID-19 cohorts (p <0.001 for both), despite a low COVID-19 prevalence. Similar results were seen in propensity-matched comparisons (≥12 hours: 19.5% vs 2.4%, p = 0.002; ≥24 hours 14.6% vs 0.0%, p = 0.001). In a predominantly rural STEMI population, delays in seeking medical care after symptom onset were markedly more frequent during the COVID-19 era, despite low COVID-19 prevalence. Considering delays in reperfusion have multiple adverse downstream consequences, these findings may have important implications in rural communities during future pandemic resurgences.


Subject(s)
COVID-19 , Myocardial Infarction , Percutaneous Coronary Intervention , ST Elevation Myocardial Infarction , COVID-19/epidemiology , Humans , Myocardial Infarction/epidemiology , Pandemics , Percutaneous Coronary Intervention/methods , Prevalence , Rural Population , ST Elevation Myocardial Infarction/diagnosis , ST Elevation Myocardial Infarction/epidemiology
6.
Catheter Cardiovasc Interv ; 99(4): 981-988, 2022 03.
Article in English | MEDLINE | ID: mdl-34967086

ABSTRACT

OBJECTIVE: This study was performed to evaluate physician radiation doses with the use of a suspended lead suit. BACKGROUND: Interventional cardiologists face substantial occupational risks from chronic radiation exposure and wearing heavy lead aprons. METHODS: Head-level physician radiation doses, collected using real-time dosimeters during consecutive coronary angiography procedures, were compared with the use of a suspended lead suit versus conventional lead aprons. Multiple linear regression analyses were completed using physician radiation doses as the response and testing patient variables (body mass index, age, sex), procedural variables (right heart catheterization, fractional flow reserve, percutaneous coronary intervention, radial access), and shielding variables (radiation-absorbing pad, accessory lead shield, suspended lead suit) as the predictors. RESULTS: Among 1054 coronary angiography procedures, 691 (65.6%) were performed with a suspended lead suit and 363 (34.4%) with lead aprons. There was no significant difference in dose area product between groups (61.7 [41.0, 94.9] mGy·cm2 vs. 64.6 [42.9, 96.9] mGy·cm2 , p = 0.20). Median head-level physician radiation doses were 10.2 [3.2, 35.5] µSv with lead aprons and 0.2 [0.1, 0.9] µSv with a suspended lead suit (p < 0.001), representing a 98.0% reduced dose with suspended lead. In the fully adjusted regression model, the use of a suspended lead suit was independently associated with a 93.8% reduction (95% confidence interval: -95.0, -92.3; p < 0.001) in physician radiation dose. CONCLUSION: Compared to conventional lead aprons, the use of a suspended lead suit during coronary angiography was associated with marked reductions in head-level physician radiation doses.


Subject(s)
Fractional Flow Reserve, Myocardial , Occupational Exposure , Physicians , Radiation Exposure , Coronary Angiography/adverse effects , Coronary Angiography/methods , Humans , Occupational Exposure/adverse effects , Occupational Exposure/prevention & control , Radiation Dosage , Radiation Exposure/adverse effects , Radiation Exposure/prevention & control , Radiography, Interventional/adverse effects , Treatment Outcome
7.
Am J Med ; 135(3): 331-333, 2022 03.
Article in English | MEDLINE | ID: mdl-34715063
8.
Am J Cardiol ; 161: 108-114, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34794607

ABSTRACT

Early repolarization pattern (ERP) is associated with increased mortality in case-control studies, but the mechanism and role of left ventricular mass (LVM) remain unclear. Our objectives were to understand (1) whether ERP associates with adverse outcomes in a multiethnic population and (2) to explore the role of LVM in these associations. Participants from the Dallas Heart Study with an electrocardiogram interpretable for ERP, defined as J point elevation ≥1 mm in 2 contiguous leads, were included. Combined all-cause mortality and nonfatal cardiovascular disease (CVD) events and individual components were assessed using Cox proportional hazards modeling after adjustment for demographics, traditional CVD risk factors, electrocardiogram intervals, and cardiac magnetic resonance imaging-derived factors. Cardiac magnetic resonance imaging-defined LVM was then added to the most fully adjusted model. Of the 2,686 participants, 240 (8.9%) demonstrated ERP. Participants with ERP were more likely to be male and Black, with lower body mass index, greater left ventricular end-diastolic volumes, and LVM. Over a median follow-up of 11 years, the combined end point occurred in 326 patients. Multivariable modeling demonstrated ERP was associated with the combined end point (HR [95% CI] 1.61 [1.14 to 2.26]), all-cause mortality (1.67 [1.00 to 2.80]). However, further adjusting for LVM attenuated the associations of ERP with the primary end point (HR [95% CI] 1.22 [0.85 to 1.77]) and secondary end points of mortality (1.39 [0.80 to 2.41]) and nonfatal CVD (1.05 [0.68 to 1.64]). ERP was associated with increased mortality and nonfatal CVD events, which was attenuated after adjusting for LVM, a previously under-recognized clinical phenotype. Previous associations of ERP with adverse cardiovascular outcomes may be partially explained by greater LVM in those with ERP.


Subject(s)
Cardiovascular Diseases/diagnosis , Electrocardiography , Heart Conduction System/physiopathology , Heart Ventricles/pathology , Magnetic Resonance Imaging, Cine/methods , Ventricular Function, Left/physiology , Adult , Aged , Cardiovascular Diseases/physiopathology , Female , Heart Ventricles/physiopathology , Humans , Male , Middle Aged , Prognosis , Survival Rate/trends , Texas/epidemiology
12.
J Am Heart Assoc ; 8(15): e010401, 2019 08 06.
Article in English | MEDLINE | ID: mdl-31337251

ABSTRACT

Background Habitual high-intensity endurance exercise is associated with increased atrial fibrillation (AF) risk and impaired cardiac conduction. It is unknown whether these observations extend to prior strength-type sports exposure. The primary aim of this study was to compare AF prevalence in former National Football League (NFL) athletes to population-based controls. The secondary aim was to characterize other conduction system parameters. Methods and Results This cross-sectional study compared former NFL athletes (n=460, age 56±12 years, black 47%) with population-based controls of similar age and racial composition from the cardiovascular cohort Dallas Heart Study-2 (n=925, age 54±9 years, black 53%). AF was present in 28 individuals (n=23 [5%] in the NFL group; n=5 [0.5%] in the control group). After controlling for other cardiovascular risk factors in multivariable regression analysis, former NFL participation remained associated with a 5.7 (95% CI: 2.1-15.9, P<0.001) higher odds ratio of AF. Older age, higher body mass index, and nonblack race were also independently associated with higher odds ratio of AF, while hypertension and diabetes mellitus were not. AF was previously undiagnosed in 15/23 of the former NFL players. Previously undiagnosed NFL players were rate controlled and asymptomatic, but 80% had a CHA2DS2-VASc score ≥1. Former NFL players also had an 8-fold higher prevalence of paced cardiac rhythms (2.0% versus 0.25%, P<0.01), compared with controls. Furthermore, former athletes had lower resting heart rates (62±11 versus 66±11 beats per minute, P<0.001), and a higher prevalence of first-degree atrioventricular block (18% versus 9%, P<0.001). Conclusions Former NFL participation was associated with an increased AF prevalence and slowed cardiac conduction when compared with a population-based control group. Former NFL athletes who screened positive for AF were generally rate controlled and asymptomatic, but 80% should have been considered for anticoagulation based on their stroke risk.


Subject(s)
Adaptation, Physiological , Atrial Fibrillation/epidemiology , Atrial Fibrillation/physiopathology , Football/physiology , Heart Conduction System/physiopathology , Adult , Black or African American/statistics & numerical data , Aged , Cross-Sectional Studies , Humans , Male , Middle Aged , Prevalence , United States , White People/statistics & numerical data
15.
Circulation ; 139(12): 1507-1516, 2019 03 19.
Article in English | MEDLINE | ID: mdl-30586729

ABSTRACT

BACKGROUND: Moderate intensity exercise is associated with a decreased incidence of atrial fibrillation. However, extensive training in competitive athletes is associated with an increased atrial fibrillation risk. We evaluated the effects of 24 months of high intensity exercise training on left atrial (LA) mechanical and electric remodeling in sedentary, healthy middle-aged adults. METHODS: Sixty-one participants (53±5 years) were randomized to 10 months of exercise training followed by 14 months of maintenance exercise or stretching/balance control. Fourteen Masters athletes were added for comparison. Left ventricular (LV) and LA volumes underwent 3D echocardiographic assessment, and signal-averaged electrocardiographs for filtered P-wave duration and atrial late potentials were completed at 0, 10, and 24 months. Extended ambulatory monitoring was performed at 0 and 24 months. Within and between group differences from baseline were compared using mixed-effects model repeated-measures analysis. RESULTS: Fifty-three participants completed the study (25 control, 28 exercise) with 88±11% adherence to assigned exercise sessions. In the exercise group, both LA and LV end diastolic volumes increased proportionately (19% and 17%, respectively) after 10 months of training (peak training load). However, only LA volumes continued to increase with an additional 14 months of exercise training (LA volumes 55%; LV end diastolic volumes 15% at 24 months versus baseline; P<0.0001 for all). The LA:LV end diastolic volumes ratio did not change from baseline to 10 months, but increased 31% from baseline in the Ex group ( P<0.0001) at 24 months, without a change in controls. There were no between group differences in the LA ejection fraction, filtered P-wave duration, atrial late potentials, and premature atrial contraction burden at 24 months and no atrial fibrillation was detected. Compared with Masters athletes, the exercise group demonstrated lower absolute LA and LV volumes, but had a similar LA:LV ratio after 24 months of training. CONCLUSIONS: Twenty-four months of high intensity exercise training resulted in LA greater than LV mechanical remodeling with no observed electric remodeling. Together, these data suggest different thresholds for electrophysiological and mechanical changes may exist in response to exercise training, and provide evidence supporting a potential mechanism by which high intensity exercise training leads to atrial fibrillation. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02039154.


Subject(s)
Atrial Function, Left/physiology , Atrial Remodeling , Exercise , Ventricular Function, Left/physiology , Athletes , Cardiovascular Diseases/diagnosis , Echocardiography, Three-Dimensional , Female , Humans , Male , Middle Aged , Postural Balance , Risk Factors
16.
Am J Cardiol ; 119(11): 1877-1882, 2017 06 01.
Article in English | MEDLINE | ID: mdl-28395892

ABSTRACT

Gender differences in J point height exist. Previous studies suggest male sex hormones mediate effects on cardiovascular disease through myocardial repolarization. Our objective was to assess whether male and female sex hormones are associated with J point amplitude in healthy subjects. We conducted a cross-sectional study of 475 healthy, mixed racial population of men, and premenopausal women (age 33 ± 9 years, 56% male). Baseline J point amplitude (JPA) was obtained from continuous surface electrocardiograms. Plasma testosterone (T), dihydrotestosterone, estrone, 17-estradiol (E2), and sex hormone-binding globulin were measured. A free testosterone index (FTI) was calculated. Multivariate regression analysis stratified by gender and electrocardiographic lead location was used to determine independent predictors of maximum JPA. Regression analysis demonstrated FTI levels were positively associated with JPA in lateral leads (ß = +0.01, p <0.05) in men but not in women. Total testosterone was positively associated with anterior electrocardiographic lead JPA in women (ß = +0.5, p <0.02), but not in men. E2 was positively associated with inferior lead JPA (ß = +1.2, p <0.03) in men but not in women. Total testosterone levels were positively associated with JPA in anterior leads (ß = +0.054, p <0.05) in women. Male volunteers in the highest tertile of FTI demonstrated greater lateral JPA compared with the lowest tertile (p <0.05). Women in the highest tertile of FTI demonstrated greater anterior lead JPA compared with the lowest tertile (p <0.05). In conclusion, in a young, healthy population, the female sex hormone E2 and an FTI are independent determinants of JPA in men, whereas T is associated with JPA in women.


Subject(s)
Aging , Cardiovascular Diseases/blood , Electrocardiography/methods , Gonadal Steroid Hormones/blood , Adult , Biomarkers/blood , Cardiovascular Diseases/physiopathology , Cross-Sectional Studies , Female , Fluoroimmunoassay , Healthy Volunteers , Humans , Male , Sex Factors
18.
Cochrane Database Syst Rev ; (10): CD011168, 2015 Oct 07.
Article in English | MEDLINE | ID: mdl-26445202

ABSTRACT

BACKGROUND: Sudden cardiac death is a significant cause of mortality in both the US and globally. However, 5% to 15% of people with sudden cardiac death have no structural abnormalities, and most of these events are attributed to underlying cardiac ion channelopathies. Rates of cardiac ion channelopathy diagnosis are increasing. However, the optimal treatment for such people is poorly understood and current guidelines rely primarily on expert opinion. OBJECTIVES: To compare the effect of implantable cardioverter defibrillators (ICD) with antiarrhythmic drugs or usual care in reducing the risk of all-cause mortality, fatal and non-fatal cardiovascular events, and adverse events in people with cardiac ion channelopathies. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL, 2015, Issue 6), EMBASE, MEDLINE, Conference Proceedings Citation Index - Science (CPCI-S), ClinicalTrials.gov, and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) in July 2015. We applied no language restrictions. SELECTION CRITERIA: We included all randomized controlled trials of people aged 18 years and older with ion channelopathies, including congenital long QT syndrome, congenital short QT syndrome, Brugada syndrome, or catecholaminergic polymorphic ventricular tachycardia. Participants must have been randomized to ICD implantation and compared to antiarrhythmic drug therapy or usual care. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies for inclusion and extracted the data. We included all-cause mortality, fatal and non-fatal cardiovascular events, and adverse events for our primary outcome analyses and non-fatal cardiovascular events, rates of inappropriate ICD firing, quality of life, and cost for our secondary outcome analyses. We calculated risk ratios (RR) and associated 95% confidence intervals (CIs) for dichotomous outcomes, both for independent and pooled study analyses. MAIN RESULTS: From the 468 references identified after removing duplicates, we found two trials comprising 86 participants that met our inclusion criteria. Both trials included participants with Brugada syndrome who were randomized to ICD versus ß-blocker therapy for secondary prevention for sudden cardiac death. Both studies were small, were performed by the same investigators, and exhibited a high risk of bias across multiple domains. In the group randomized to ICD therapy, there was a nine-fold lower risk of mortality compared with people randomized to medical therapy (0% with ICD versus 18% with medical therapy; RR 0.11, 95% CI 0.01 to 0.83; 2 trials, 86 participants). There was low quality evidence of a difference in the rates of combined fatal and non-fatal cardiovascular events, and the results were imprecise (26% with ICD versus 18% with medical therapy; RR 1.49, 95% CI 0.66 to 3.34; 2 trials, 86 participants). The rates of adverse events were higher in the ICD group, but these results were imprecise (28% with ICD versus 10% with medical therapy; RR 2.44, 95% CI 0.92 to 6.44; 2 trials, 86 participants). For secondary outcomes, the risk of non-fatal cardiovascular events was higher in the ICD group, but these results were imprecise and were driven entirely by appropriate ICD-termination of cardiac arrhythmias (26% with ICD versus 0% with medical therapy; RR 11.4, 95% CI 1.57 to 83.3; 2 trials, 86 participants). Approximately 25% of the ICD group experienced inappropriate ICD firing, all of which was corrected by device reprogramming. No data were available for quality of life or cost. We considered the quality of evidence low using the GRADE methodology, due to study limitations and imprecision of effects. AUTHORS' CONCLUSIONS: Among people with Brugada syndrome who have survived a prior episode of sudden cardiac death, ICD therapy appeared to reduce mortality when compared to ß-blocker therapy, but the true magnitude may be substantially different from the estimate of the effect because of study limitations and imprecision. Due to the large magnitude of effect, it is unlikely that there will be additional studies evaluating the role of ICDs for secondary prevention in this population. Further studies are necessary to determine the optimal treatment, if any, to prevent an initial episode of sudden cardiac death in people with cardiac ion channelopathies.


Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Brugada Syndrome/therapy , Channelopathies/therapy , Death, Sudden, Cardiac/prevention & control , Defibrillators, Implantable , Secondary Prevention/methods , Adrenergic beta-Antagonists/adverse effects , Brugada Syndrome/etiology , Channelopathies/complications , Death, Sudden, Cardiac/etiology , Defibrillators, Implantable/adverse effects , Heart Diseases/therapy , Humans , Randomized Controlled Trials as Topic
20.
Infect Immun ; 77(12): 5389-99, 2009 Dec.
Article in English | MEDLINE | ID: mdl-19752036

ABSTRACT

Changes in airway dynamics have been reported in the rat model of pulmonary cryptococcosis. However, it is not known if Cryptococcus neoformans-induced changes in lung functions are related to the immunophenotype that develops in response to cryptococcal infection in the lungs. In this study we performed a parallel analysis of the immunophenotype and airway resistance (standard resistance of the airways [SRAW]) in BALB/c mice infected with highly virulent C. neoformans strain H99 and moderately virulent strain 52D. H99 infection evoked a Th2 response and was associated with increased SRAW, while the SRAW for 52D infection, which resulted in a predominantly Th1-skewed response, did not differ from the SRAW for uninfected mice. We found that an altered SRAW in mice did not positively or negatively correlate with the pulmonary fungal burden, the magnitude of inflammatory response, the numbers of T cells, eosinophils or eosinophil subsets, neutrophils, or monocytes/macrophages, or the levels of cytokines (interleukin-4 [IL-4], IL-10, gamma interferon, or IL-13) produced by lung leukocytes. However, the level of a systemic Th2 marker, serum immunoglobulin E (IgE), correlated significantly with SRAW, indicating that the changes in lung functions were proportional to the level of Th2 skewing in this model. These data also imply that IgE may contribute to the altered SRAW observed in H99-infected mice. Lung histological analysis revealed severe allergic bronchopulmonary mycosis pathology in H99-infected mice and evidence of protective responses in 52D-infected mice with well-marginalized lesions. Taken together, the data show that C. neoformans can significantly affect airflow physiology, particularly in the context of a Th2 immune response with possible involvement of IgE as an important factor.


Subject(s)
Cryptococcosis/immunology , Cryptococcus neoformans/immunology , Lung Diseases, Fungal/immunology , Lung/pathology , Lung/physiopathology , Th1 Cells/immunology , Th2 Cells/immunology , Animals , Brain/microbiology , Colony Count, Microbial , Cryptococcosis/pathology , Female , Immunoglobulin E/blood , Inflammation/pathology , Inflammation Mediators/analysis , Leukocytes/immunology , Lung/chemistry , Lung/microbiology , Lung Diseases, Fungal/pathology , Mice , Mice, Inbred BALB C , Rats , Respiratory Function Tests
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