Denervated Myocardium Is Preferentially Associated With Sudden Cardiac Arrest in Ischemic Cardiomyopathy: A Pilot Competing Risks Analysis of Cause-Specific Mortality
James A Fallavollita, Jonathan D Dare, Randolph L Carter, Sunil Baldwa, John M Canty Jr, James A Fallavollita, Jonathan D Dare, Randolph L Carter, Sunil Baldwa, John M Canty Jr
Abstract
Background: 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.
Methods and results: 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.
Conclusions: 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.
Clinical trial registration: URL: https://ichgcp.net/clinical-trials-registry/NCT01400334" title="See in ClinicalTrials.gov">NCT01400334.
Keywords: coronary artery disease; death, sudden, cardiac; defibrillators, implantable; heart failure; positron-emission tomography; risk factors.
© 2017 American Heart Association, Inc.
Figures
![Figure 1. Cumulative Distribution Functions for Sudden…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f1.jpg)
![Figure 2. Cumulative Distribution Functions for Variables…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f2.jpg)
![Figure 3. Cumulative Distribution Functions for Variables…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f3.jpg)
Figure 4. Cumulative Distribution Functions for Variables…
Figure 4. Cumulative Distribution Functions for Variables Preferentially Associated with Non-Sudden Cardiac Death
Resting heart…
Figure 5. Estimated Event Rates from the…
Figure 5. Estimated Event Rates from the Competing Risks Analysis for Variables Preferentially Associated with…
Figure 6. Estimated Event Rates from the…
Figure 6. Estimated Event Rates from the Competing Risks Analysis for Variables Preferentially Associated with…
- Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy.Fallavollita JA, Heavey BM, Luisi AJ Jr, Michalek SM, Baldwa S, Mashtare TL Jr, Hutson AD, Dekemp RA, Haka MS, Sajjad M, Cimato TR, Curtis AB, Cain ME, Canty JM Jr. Fallavollita JA, et al. J Am Coll Cardiol. 2014 Jan 21;63(2):141-9. doi: 10.1016/j.jacc.2013.07.096. Epub 2013 Sep 25. J Am Coll Cardiol. 2014. PMID: 24076296 Free PMC article. Clinical Trial.
- Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.Wu KC, Gerstenblith G, Guallar E, Marine JE, Dalal D, Cheng A, Marbán E, Lima JA, Tomaselli GF, Weiss RG. Wu KC, et al. Circ Cardiovasc Imaging. 2012 Mar;5(2):178-86. doi: 10.1161/CIRCIMAGING.111.968024. Epub 2012 Jan 20. Circ Cardiovasc Imaging. 2012. PMID: 22267750 Free PMC article.
- Impact of denervated myocardium on improving risk stratification for sudden cardiac death.Cain ME. Cain ME. Trans Am Clin Climatol Assoc. 2014;125:141-53; discussion 153. Trans Am Clin Climatol Assoc. 2014. PMID: 25125727 Free PMC article.
- Ambulatory blood pressure monitoring, 2D-echo and clinical variables relating to cardiac events in ischaemic cardiomyopathy following cardioverter-defibrillator implantation.Antonini L, Pasceri V, Mollica C, Ficili S, Poti G, Aquilani S, Santini M, La Rocca S. Antonini L, et al. J Cardiovasc Med (Hagerstown). 2011 May;12(5):334-9. doi: 10.2459/JCM.0b013e3283410368. J Cardiovasc Med (Hagerstown). 2011. PMID: 21487343
- Electrophysiology testing for risk stratification of patients with ischaemic cardiomyopathy: a call for action.Katritsis DG, Zografos T, Hindricks G. Katritsis DG, et al. Europace. 2018 Sep 1;20(FI2):f148-f152. doi: 10.1093/europace/eux305. Europace. 2018. PMID: 29236981 Review.
- Comorbid Hypertension Reduces the Risk of Ventricular Arrhythmia in Chronic Heart Failure Patients with Implantable Cardioverter-Defibrillators.Huang H, Deng Y, Cheng S, Zhang N, Cai M, Niu H, Chen X, Gu M, Liu X, Yu Y, Hua W. Huang H, et al. J Clin Med. 2022 May 17;11(10):2816. doi: 10.3390/jcm11102816. J Clin Med. 2022. PMID: 35628944 Free PMC article.
- Study on Risk Factors for Death from Cardiomyopathy and Effectiveness of Health Information Management.Wang L, Zhang S, Wang Y, Xuan J, Han Y, Ke J. Wang L, et al. J Healthc Eng. 2021 Dec 7;2021:3922611. doi: 10.1155/2021/3922611. eCollection 2021. J Healthc Eng. 2021. PMID: 34917304 Free PMC article.
- Does quantification of [11C]meta-hydroxyephedrine and [13N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.Wang JZ, Zelt JGE, Kaps N, Lavallee A, Renaud JM, Rotstein B, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Wang JZ, et al. J Nucl Cardiol. 2022 Apr;29(2):413-425. doi: 10.1007/s12350-021-02732-5. Epub 2021 Aug 2. J Nucl Cardiol. 2022. PMID: 34341953 Free PMC article.
- Molecular Imaging Using Cardiac PET/CT: Opportunities to Harmonize Diagnosis and Therapy.Thackeray JT. Thackeray JT. Curr Cardiol Rep. 2021 Jul 1;23(8):96. doi: 10.1007/s11886-021-01526-y. Curr Cardiol Rep. 2021. PMID: 34196821 Free PMC article. Review.
- Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy.Zelt JGE, Wang JZ, Mielniczuk LM, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Zelt JGE, et al. Circ Cardiovasc Imaging. 2021 Jun;14(6):e012549. doi: 10.1161/CIRCIMAGING.121.012549. Epub 2021 Jun 9. Circ Cardiovasc Imaging. 2021. PMID: 34102857 Free PMC article. Clinical Trial.
- Aged
- Cardiomyopathies / diagnosis
- Cardiomyopathies / mortality
- Cardiomyopathies / physiopathology
- Cardiomyopathies / therapy*
- Cause of Death
- Chi-Square Distribution
- Clinical Decision-Making
- Death, Sudden, Cardiac / etiology
- Death, Sudden, Cardiac / prevention & control*
- Defibrillators, Implantable
- Disease Progression
- Echocardiography
- Electric Countershock* / adverse effects
- Electric Countershock* / instrumentation
- Electric Countershock* / mortality
- Electrocardiography
- Female
- Heart / innervation*
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Multivariate Analysis
- Myocardial Ischemia / diagnosis
- Myocardial Ischemia / mortality
- Myocardial Ischemia / physiopathology
- Myocardial Ischemia / therapy*
- Myocardium / pathology
- Patient Selection
- Pilot Projects
- Positron-Emission Tomography
- Primary Prevention / instrumentation
- Primary Prevention / methods*
- Risk Assessment
- Risk Factors
- Time Factors
- Tissue Survival
- Treatment Outcome
- Ventricular Function, Left
- ClinicalTrials.gov/NCT01400334
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
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![Figure 4. Cumulative Distribution Functions for Variables…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f4.jpg)
![Figure 5. Estimated Event Rates from the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f5.jpg)
Figure 6. Estimated Event Rates from the…
Figure 6. Estimated Event Rates from the Competing Risks Analysis for Variables Preferentially Associated with…
- Regional myocardial sympathetic denervation predicts the risk of sudden cardiac arrest in ischemic cardiomyopathy.Fallavollita JA, Heavey BM, Luisi AJ Jr, Michalek SM, Baldwa S, Mashtare TL Jr, Hutson AD, Dekemp RA, Haka MS, Sajjad M, Cimato TR, Curtis AB, Cain ME, Canty JM Jr. Fallavollita JA, et al. J Am Coll Cardiol. 2014 Jan 21;63(2):141-9. doi: 10.1016/j.jacc.2013.07.096. Epub 2013 Sep 25. J Am Coll Cardiol. 2014. PMID: 24076296 Free PMC article. Clinical Trial.
- Combined cardiac magnetic resonance imaging and C-reactive protein levels identify a cohort at low risk for defibrillator firings and death.Wu KC, Gerstenblith G, Guallar E, Marine JE, Dalal D, Cheng A, Marbán E, Lima JA, Tomaselli GF, Weiss RG. Wu KC, et al. Circ Cardiovasc Imaging. 2012 Mar;5(2):178-86. doi: 10.1161/CIRCIMAGING.111.968024. Epub 2012 Jan 20. Circ Cardiovasc Imaging. 2012. PMID: 22267750 Free PMC article.
- Impact of denervated myocardium on improving risk stratification for sudden cardiac death.Cain ME. Cain ME. Trans Am Clin Climatol Assoc. 2014;125:141-53; discussion 153. Trans Am Clin Climatol Assoc. 2014. PMID: 25125727 Free PMC article.
- Ambulatory blood pressure monitoring, 2D-echo and clinical variables relating to cardiac events in ischaemic cardiomyopathy following cardioverter-defibrillator implantation.Antonini L, Pasceri V, Mollica C, Ficili S, Poti G, Aquilani S, Santini M, La Rocca S. Antonini L, et al. J Cardiovasc Med (Hagerstown). 2011 May;12(5):334-9. doi: 10.2459/JCM.0b013e3283410368. J Cardiovasc Med (Hagerstown). 2011. PMID: 21487343
- Electrophysiology testing for risk stratification of patients with ischaemic cardiomyopathy: a call for action.Katritsis DG, Zografos T, Hindricks G. Katritsis DG, et al. Europace. 2018 Sep 1;20(FI2):f148-f152. doi: 10.1093/europace/eux305. Europace. 2018. PMID: 29236981 Review.
- Comorbid Hypertension Reduces the Risk of Ventricular Arrhythmia in Chronic Heart Failure Patients with Implantable Cardioverter-Defibrillators.Huang H, Deng Y, Cheng S, Zhang N, Cai M, Niu H, Chen X, Gu M, Liu X, Yu Y, Hua W. Huang H, et al. J Clin Med. 2022 May 17;11(10):2816. doi: 10.3390/jcm11102816. J Clin Med. 2022. PMID: 35628944 Free PMC article.
- Study on Risk Factors for Death from Cardiomyopathy and Effectiveness of Health Information Management.Wang L, Zhang S, Wang Y, Xuan J, Han Y, Ke J. Wang L, et al. J Healthc Eng. 2021 Dec 7;2021:3922611. doi: 10.1155/2021/3922611. eCollection 2021. J Healthc Eng. 2021. PMID: 34917304 Free PMC article.
- Does quantification of [11C]meta-hydroxyephedrine and [13N]ammonia kinetics improve risk stratification in ischemic cardiomyopathy.Wang JZ, Zelt JGE, Kaps N, Lavallee A, Renaud JM, Rotstein B, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Wang JZ, et al. J Nucl Cardiol. 2022 Apr;29(2):413-425. doi: 10.1007/s12350-021-02732-5. Epub 2021 Aug 2. J Nucl Cardiol. 2022. PMID: 34341953 Free PMC article.
- Molecular Imaging Using Cardiac PET/CT: Opportunities to Harmonize Diagnosis and Therapy.Thackeray JT. Thackeray JT. Curr Cardiol Rep. 2021 Jul 1;23(8):96. doi: 10.1007/s11886-021-01526-y. Curr Cardiol Rep. 2021. PMID: 34196821 Free PMC article. Review.
- Positron Emission Tomography Imaging of Regional Versus Global Myocardial Sympathetic Activity to Improve Risk Stratification in Patients With Ischemic Cardiomyopathy.Zelt JGE, Wang JZ, Mielniczuk LM, Beanlands RSB, Fallavollita JA, Canty JM Jr, deKemp RA. Zelt JGE, et al. Circ Cardiovasc Imaging. 2021 Jun;14(6):e012549. doi: 10.1161/CIRCIMAGING.121.012549. Epub 2021 Jun 9. Circ Cardiovasc Imaging. 2021. PMID: 34102857 Free PMC article. Clinical Trial.
- Aged
- Cardiomyopathies / diagnosis
- Cardiomyopathies / mortality
- Cardiomyopathies / physiopathology
- Cardiomyopathies / therapy*
- Cause of Death
- Chi-Square Distribution
- Clinical Decision-Making
- Death, Sudden, Cardiac / etiology
- Death, Sudden, Cardiac / prevention & control*
- Defibrillators, Implantable
- Disease Progression
- Echocardiography
- Electric Countershock* / adverse effects
- Electric Countershock* / instrumentation
- Electric Countershock* / mortality
- Electrocardiography
- Female
- Heart / innervation*
- Humans
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Multivariate Analysis
- Myocardial Ischemia / diagnosis
- Myocardial Ischemia / mortality
- Myocardial Ischemia / physiopathology
- Myocardial Ischemia / therapy*
- Myocardium / pathology
- Patient Selection
- Pilot Projects
- Positron-Emission Tomography
- Primary Prevention / instrumentation
- Primary Prevention / methods*
- Risk Assessment
- Risk Factors
- Time Factors
- Tissue Survival
- Treatment Outcome
- Ventricular Function, Left
- ClinicalTrials.gov/NCT01400334
- Full Text Sources
- Other Literature Sources
- Medical
![Figure 6. Estimated Event Rates from the…](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/5555076/bin/nihms890818f6.jpg)
Source: PubMed