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Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

ABSTRACT: Previous studies have identified multiple risk factors that are associated with total cardiac mortality. Nevertheless, identifying specific factors that distinguish patients at risk of arrhythmic death versus heart failure could better target patients likely to benefit from implantable cardiac defibrillators, which have no impact on nonsudden cardiac death.We performed a pilot competing risks analysis of the National Institutes of Health-sponsored PAREPET trial (Prediction of Arrhythmic Events with Positron Emission Tomography). Death from cardiac causes was ascertained in subjects with ischemic cardiomyopathy (n=204) eligible for an implantable cardiac defibrillator for the primary prevention of sudden cardiac arrest after baseline clinical evaluation and imaging at enrollment (positron emission tomography and 2-dimensional echo). Mean age was 67±11 years with an ejection fraction of 27±9%, and 90% were men. During 4.1 years of follow-up, there were 33 sudden cardiac arrests (arrhythmic death or implantable cardiac defibrillator discharge for ventricular fibrillation or ventricular tachycardia >240 bpm) and 36 nonsudden cardiac deaths. Sudden cardiac arrest was correlated with a greater volume of denervated myocardium (defect of the positron emission tomography norepinephrine analog 11C-hydroxyephedrine), lack of angiotensin inhibition therapy, elevated B-type natriuretic peptide, and larger left ventricular end-diastolic volume index. In contrast, nonsudden cardiac death was associated with a higher resting heart rate, older age, elevated creatinine, larger left atrial volume index, and larger left ventricular end-diastolic volume index.Distinct clinical, laboratory, and imaging variables are associated with cause-specific cardiac mortality in primary-prevention candidates with ischemic cardiomyopathy. If prospectively validated, these multivariable associations may help target specific therapies to those at the greatest risk of sudden and nonsudden cardiac death.URL: https://clinicaltrials.gov. Unique identifier: NCT01400334.

SUBMITTER: Fallavollita JA

PROVIDER: S-EPMC5555076 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature

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Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

Fallavollita James A JA Dare Jonathan D JD Carter Randolph L RL Baldwa Sunil S Canty John M JM

Circulation. Cardiovascular imaging 20170801 8

<h4>Background</h4>Previous studies have identified multiple risk factors that are associated with total cardiac mortality. Nevertheless, identifying specific factors that distinguish patients at risk of arrhythmic death versus heart failure could better target patients likely to benefit from implantable cardiac defibrillators, which have no impact on nonsudden cardiac death.<h4>Methods and results</h4>We performed a pilot competing risks analysis of the National Institutes of Health-sponsored P ...[more]

PMID: 28794139

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Project description:OBJECTIVES:The PAREPET (Prediction of ARrhythmic Events with Positron Emission Tomography) study sought to test the hypothesis that quantifying inhomogeneity in myocardial sympathetic innervation could identify patients at highest risk for sudden cardiac arrest (SCA). BACKGROUND:Left ventricular ejection fraction (LVEF) is the only parameter identifying patients at risk of SCA who benefit from an implantable cardiac defibrillator (ICD). METHODS:We prospectively enrolled 204 subjects with ischemic cardiomyopathy (LVEF ?35%) eligible for primary prevention ICDs. Positron emission tomography (PET) was used to quantify myocardial sympathetic denervation ((11)C-meta-hydroxyephedrine [(11)C-HED]), perfusion ((13)N-ammonia) and viability (insulin-stimulated (18)F-2-deoxyglucose). The primary endpoint was SCA defined as arrhythmic death or ICD discharge for ventricular fibrillation or ventricular tachycardia >240 beats/min. RESULTS:After 4.1 years follow-up, cause-specific SCA was 16.2%. Infarct volume (22 ± 7% vs. 19 ± 9% of left ventricle [LV]) and LVEF (24 ± 8% vs. 28 ± 9%) were not predictors of SCA. In contrast, patients developing SCA had greater amounts of sympathetic denervation (33 ± 10% vs. 26 ± 11% of LV; p = 0.001) reflecting viable, denervated myocardium. The lower tertiles of sympathetic denervation had SCA rates of 1.2%/year and 2.2%/year, whereas the highest tertile had a rate of 6.7%/year. Multivariate predictors of SCA were PET sympathetic denervation, left ventricular end-diastolic volume index, creatinine, and no angiotensin inhibition. With optimized cut-points, the absence of all 4 risk factors identified low risk (44% of cohort; SCA <1%/year); whereas ?2 factors identified high risk (20% of cohort; SCA ?12%/year). CONCLUSIONS:In ischemic cardiomyopathy, sympathetic denervation assessed using (11)C-HED PET predicts cause-specific mortality from SCA independently of LVEF and infarct volume. This may provide an improved approach for the identification of patients most likely to benefit from an ICD. (Prediction of ARrhythmic Events With Positron Emission Tomography [PAREPET]; NCT01400334).

Project description:IntroductionParotid-gland carcinoma (PGC) is a relatively rare tumor that comprises a group of heterogeneous histologic subtypes. We used the Surveillance, Epidemiology, and End Results (SEER) program database to apply a competing-risks analysis to PGC patients, and then established and validated predictive nomograms for PGC.MethodsSpecific screening criteria were applied to identify PGC patients and extract their clinical and other characteristics from the SEER database. We used the cumulative incidence function to estimate the cumulative incidence rates of PGC-specific death (GCD) and other cause-specific death (OCD), and tested for differences between groups using Gray's test. We then identified independent prognostic factors by applying the Fine-Gray proportional subdistribution hazard approach, and constructed predictive nomograms based on the results. Calibration curves and the concordance index (C-index) were employed to validate the nomograms.ResultsWe finally identified 4,075 eligible PGC patients who had been added to the SEER database from 2004 to 2015. Their 1-, 3-, and 5-year cumulative incidence rates of GCD were 10.1%, 21.6%, and 25.7%, respectively, while those of OCD were 2.9%, 6.6%, and 9.0%. Age, race, World Health Organization histologic risk classification, differentiation grade, American Joint Committee on Cancer (AJCC) T stage, AJCC N stage, AJCC M stage, and RS (radiotherapy and surgery status) were independent predictors of GCD, while those of OCD were age, sex, marital status, AJCC T stage, AJCC M stage, and RS. These factors were integrated for constructing predictive nomograms. The results for calibration curves and the C-index suggested that the nomograms were well calibrated and had good discrimination ability.ConclusionWe have used the SEER database to establish-to the best of our knowledge-the first competing-risks nomograms for predicting the 1-, 3-, and 5-year cause-specific mortality in PGC. The nomograms showed relatively good performance and can be used in clinical practice to assist clinicians in individualized treatment decision-making.

Dataset Information

Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

Publications

Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality.

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