Advertisement

Comparison of Frequency of Ventricular Tachyarrhythmia in Men-Versus-Women in Patients with Implantable Cardioverter-Defibrillator for Primary Prevention

      Current guidelines do not account for possible sex differences in the risk of ventricular tachyarrhythmia (VTA). We sought to identify specific factors associated with increased risk for VTA in women implanted with a primary prevention implantable cardioverter-defibrillator (ICD). Our study cohort consisted of 4,506 patients with an ICD or cardiac resynchronization therapy-defibrillator who were enrolled in the 4 landmark MADIT studies - MADIT-II, MADIT-RISK, MADIT-CRT and MADIT-RIT (1,075 women [24%]). Fine and Gray regression models were used to identify female-specific risk factors for the primary end point of VTA, defined as ICD-recorded, treated, or monitored, sustained ventricular tachycardia ≥170 beats per minute or ventricular fibrillation. At 3.5 years of follow-up, the cumulative incidence of VTA was significantly lower in women than men (17% vs 26%, respectively; p <0.001 for the entire follow-up). Use of amiodarone at enrollment, Black race, and history of previous myocardial infarction without previous revascularization was found to be independent risk factors of VTA in women. Of these factors, only Black race was associated with a statistically significant risk increase in men. At 3.5 years, the cumulative incidence of VTA in women with one or more of these risk factors was 27% compared with 14% in women with none of the risk factors (hazard ratio [confidence interval] = 2.08 [1.49 to 2.91]). In conclusion, our study, comprising 4 landmark ICD clinical trials, shows that sex and race have the potential to be used for improved risk stratification of patients who are candidates for primary prevention ICD.
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Bardy GH
        • Lee KL
        • Mark DB
        • Poole JE
        • Packer DL
        • Boineau R
        • Domanski M
        • Troutman C
        • Anderson J
        • Johnson G
        • McNulty SE
        • Clapp-Channing N
        • Davidson-Ray LD
        • Fraulo ES
        • Fishbein DP
        • Luceri RM
        • Ip JH
        Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT) Investigators. Amiodarone or an implantable cardioverter-defibrillator for congestive heart failure.
        N Engl J Med. 2005; 352: 225-237
        • Buxton AE
        • Lee KL
        • Fisher JD
        • Josephson ME
        • Prystowsky EN
        • Hafley G.
        A randomized study of the prevention of sudden death in patients with coronary artery disease. Multicenter unsustained tachycardia Trial Investigators.
        N Engl J Med. 1999; 341: 1882-1890
        • Kadish A
        • Dyer A
        • Daubert JP
        • Quigg R
        • Estes NA
        • Anderson KP
        • Calkins H
        • Hoch D
        • Goldberger J
        • Shalaby A
        • Sanders WE
        • Schaechter A
        • Levine JH
        Defibrillators in Nonischemic Cardiomyopathy Treatment Evaluation (DEFINITE) Investigators. Prophylactic defibrillator implantation in patients with nonischemic dilated cardiomyopathy.
        N Engl J Med. 2004; 350: 2151-2158
        • Moss AJ
        • Hall WJ
        • Cannom DS
        • Daubert JP
        • Higgins SL
        • Klein H
        • Levine JH
        • Saksena S
        • Waldo AL
        • Wilber D
        • Brown MW
        • Heo M.
        Improved survival with an implanted defibrillator in patients with coronary disease at high risk for ventricular arrhythmia. Multicenter Automatic Defibrillator Implantation Trial Investigators.
        N Engl J Med. 1996; 335: 1933-1940
        • Moss AJ
        • Hall WJ
        • Cannom DS
        • Klein H
        • Brown MW
        • Daubert JP
        • Estes 3rd, NA
        • Foster E
        • Greenberg H
        • Higgins SL
        • Pfeffer MA
        • Solomon SD
        • Wilber D
        • Zareba W
        MADIT-CRT Trial Investigators. Cardiac-resynchronization therapy for the prevention of heart-failure events.
        N Engl J Med. 2009; 361: 1329-1338
        • Moss AJ
        • Zareba W
        • Hall WJ
        • Klein H
        • Wilber DJ
        • Cannom DS
        • Daubert JP
        • Higgins SL
        • Brown MW
        • Andrews ML
        Multicenter Automatic Defibrillator Implantation Trial II Investigators. Prophylactic implantation of a defibrillator in patients with myocardial infarction and reduced ejection fraction.
        N Engl J Med. 2002; 346: 877-883
        • Conen D
        • Arendacká B
        • Röver C
        • Bergau L
        • Munoz P
        • Wijers S
        • Sticherling C
        • Zabel M
        • Friede T.
        Gender differences in appropriate shocks and mortality among patients with primary prophylactic implantable cardioverter-defibrillators: systematic review and meta-analysis.
        PLoS ONE. 2016; 11e0162756
        • MacFadden DR
        • Crystal E
        • Krahn AD
        • Mangat I
        • Healey JS
        • Dorian P
        • Birnie D
        • Simpson CS
        • Khaykin Y
        • Pinter A
        • Nanthakumar K
        • Calzavara AJ
        • Austin PC
        • Tu JV
        • Lee DS
        Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database.
        Ann Intern Med. 2012; 156: 195-203
        • Zaman S
        • Deshmukh T
        • Aslam A
        • Martin C
        • Kovoor P.
        Sex differences in electrophysiology, ventricular tachyarrhythmia, cardiac arrest and sudden cardiac death following acute myocardial infarction.
        Heart Lung Circ. 2020; 29: 1025-1031
      1. Zareba W. Risk Stratification in MADIT II Type Patients; 2011.

        • Moss AJ
        • Schuger C
        • Beck CA
        • Brown MW
        • Cannom DS
        • Daubert JP
        • Estes 3rd, NA
        • Greenberg H
        • Hall WJ
        • Huang DT
        • Kautzner J
        • Klein H
        • McNitt S
        • Olshansky B
        • Shoda M
        • Wilber D
        • Zareba W
        MADIT-RIT Trial Investigators. Reduction in inappropriate therapy and mortality through ICD programming.
        N Engl J Med. 2012; 367: 2275-2283
        • Albert CM
        • Quigg R
        • Saba S
        • Estes 3rd, NA
        • Shaechter A
        • Subacius H
        • Howard A
        • Levine J
        • Kadish A
        DEFINITE Investigators. Sex differences in outcome after implantable cardioverter defibrillator implantation in nonischemic cardiomyopathy.
        Am Heart J. 2008; 156: 367-372
        • Russo AM
        • Poole JE
        • Mark DB
        • Anderson J
        • Hellkamp AS
        • Lee KL
        • Johnson GW
        • Domanski M
        • Bardy GH.
        Primary prevention with defibrillator therapy in women: results from the sudden cardiac death in Heart Failure Trial.
        J Cardiovasc Electrophysiol. 2008; 19: 720-724
        • van der Heijden AC
        • Thijssen J
        • Borleffs CJ
        • van Rees JB
        • Höke U
        • van der Velde ET
        • van Erven L
        • Schalij MJ.
        Gender-specific differences in clinical outcome of primary prevention implantable cardioverter defibrillator recipients.
        Heart. 2013; 99: 1244-1249
        • Santangeli P
        • Pelargonio G
        • Dello Russo A
        • Casella M
        • Bisceglia C
        • Bartoletti S
        • Santarelli P
        • Di Biase L
        • Natale A
        Gender differences in clinical outcome and primary prevention defibrillator benefit in patients with severe left ventricular dysfunction: a systematic review and meta-analysis.
        Heart Rhythm. 2010; 7: 876-882
        • Loring Z
        • Strauss DG
        • Gerstenblith G
        • Tomaselli GF
        • Weiss RG
        • Wu KC.
        Cardiac MRI scar patterns differ by sex in an implantable cardioverter-defibrillator and cardiac resynchronization therapy cohort.
        Heart Rhythm. 2013; 10: 659-665
        • Fischer TH
        • Herting J
        • Eiringhaus J
        • Pabel S
        • Hartmann NH
        • Ellenberger D
        • Friedrich M
        • Renner A
        • Gummert J
        • Maier LS
        • Zabel M
        • Hasenfuss G
        • Sossalla S.
        Sex-dependent alterations of Ca2+ cycling in human cardiac hypertrophy and heart failure.
        Europace. 2016; 18: 1440-1448
        • Li Y
        • Kishimoto I
        • Saito Y
        • Harada M
        • Kuwahara K
        • Izumi T
        • Hamanaka I
        • Takahashi N
        • Kawakami R
        • Tanimoto K
        • Nakagawa Y
        • Nakanishi M
        • Adachi Y
        • Garbers DL
        • Fukamizu A
        • Nakao K.
        Androgen contributes to gender-related cardiac hypertrophy and fibrosis in mice lacking the gene encoding guanylyl cyclase-A.
        Endocrinology. 2004; 145: 951-958
        • de Sousa MR
        • Morillo CA
        • Rabelo FT
        • Nogueira Filho AM
        • Ribeiro AL
        Non-sustained ventricular tachycardia as a predictor of sudden cardiac death in patients with left ventricular dysfunction: a meta-analysis.
        Eur J Heart Fail. 2008; 10: 1007-1014
        • Verma A
        • Sarak B
        • Kaplan AJ
        • Oosthuizen R
        • Beardsall M
        • Wulffhart Z
        • Higenbottam J
        • Khaykin Y.
        Predictors of appropriate implantable cardioverter defibrillator (ICD) therapy in primary prevention patients with ischemic and nonischemic cardiomyopathy.
        Pacing Clin Electrophysiol. 2010; 33: 320-329
        • Middlekauff HR
        • Stevenson WG
        • Stevenson LW.
        Prognostic significance of atrial fibrillation in advanced heart failure. A study of 390 patients.
        Circulation. 1991; 84: 40-48
        • Fender EA
        • Henrikson CA
        • Tereshchenko L.
        Racial differences in sudden cardiac death.
        J Electrocardiol. 2014; 47: 815-818
      2. Zhao D, Post WS, Blasco-Colmenares E, Cheng A, Zhang Y, DEO, Deo R, Pastor-Barriuso R, Michos ED, Sotoodehnia N, Guallar E. Racial differences in sudden cardiac death. Circulation Sotoodehnia N, Guallar E, ed. 2019;139:1688–1697.

        • Ackerman MJ
        • Splawski I
        • Makielski JC
        • Tester DJ
        • Will ML
        • Timothy KW
        • Keating MT
        • Jones G
        • Chadha M
        • Burrow CR
        • Stephens JC
        • Xu C
        • Judson R
        • Curran ME
        Spectrum and prevalence of cardiac sodium channel variants among Black, White, Asian, and Hispanic individuals: implications for arrhythmogenic susceptibility and Brugada/long QT syndrome genetic testing.
        Heart Rhythm. 2004; 1: 600-607
        • Ackerman MJ
        • Tester DJ
        • Jones GS
        • Will ML
        • Burrow CR
        • Curran ME.
        Ethnic differences in cardiac potassium channel variants: implications for genetic susceptibility to sudden cardiac death and genetic testing for congenital long QT syndrome.
        Mayo Clin Proc. 2003; 78: 1479-1487
      3. Akylbekova EL, Payne JP, Newton-Cheh C, May WL, Fox ER, Wilson JG, Sarpong DF, Taylor HA, Maher JF. Gene-environment interaction between SCN5A-1103Y and hypokalemia influences QT interval prolongation in African Americans: the Jackson Heart Study. Am Heart J2014;167:116–122.e1.

        • Burke A
        • Creighton W
        • Mont E
        • Li L
        • Hogan S
        • Kutys R
        • Fowler D
        • Virmani R.
        Role of SCN5A Y1102 polymorphism in sudden cardiac death in blacks.
        Circulation. 2005; 112: 798-802
        • Fang J
        • Alderman MH.
        Gender differences of revascularization in patients with acute myocardial infarction.
        Am J Cardiol. 2006; 97: 1722-1726
        • Khera S
        • Kolte D
        • Gupta T
        • Subramanian KS
        • Khanna N
        • Aronow WS
        • Ahn C
        • Timmermans RJ
        • Cooper HA
        • Fonarow GC
        • Frishman WH
        • Panza JA
        • Bhatt DL.
        Temporal trends and sex differences in revascularization and outcomes of ST-segment elevation myocardial infarction in younger adults in the United States.
        J Am Coll Cardiol. 2015; 66: 1961-1972