Curr Atheroscler Rep (2015) 17: 33 DOI 10.1007/s11883-015-0512-y
WOMEN AND ISCHEMIC HEART DISEASE (M GULATI, SECTION EDITOR)
ICD and CRT Use in Ischemic Heart Disease in Women Nishaki Kiran Mehta 1 & William T. Abraham 2 & Melanie Maytin 3
Published online: 29 April 2015 # Springer Science+Business Media New York 2015
Abstract Although the role of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) in improving outcomes in ischemic cardiomyopathy (ICM) has been described, the data regarding gender-based survival outcomes are limited. There is a higher preponderance of nonischemic cardiomyopathy (NICM) in women, and most of the ICM literature is derived from sub-study analysis. This review summarizes the current body of literature on prognosis, pathophysiology, and the present clinical practice for device implantation in women with ICM. Keywords Cardiac resynchronization therapy . Gender differences . Implantable cardioverter defibrillator . Ischemic cardiomyopathy
Introduction The role of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) is well established in improving clinical outcomes in patients with ischemic This article is part of the Topical Collection on Women and Ischemic Heart Disease
cardiomyopathy (ICM) [1–7]. The Multicenter Automatic Defibrillator Implantation Trial (MADIT II trial) is one of the several landmark trials that have demonstrated a marked mortality reduction in post-infarction patients with severely depressed left ventricular function [8]. Despite the demonstrated overall survival benefit with cardiac implantable electronic device (CIED) therapy, data regarding sex-based survival differences are limited. Studies have suggested that women tend to benefit less from primary prevention ICD therapy [9, 10] and, yet, derive more benefit from CRT, with echocardiographic evidence of reverse remodeling [11, 12••, 13, 14]. Whether these data are accurate remains to be understood. The major caveats that limit a complete understanding of the role of sex in ICM stem from: under-representation of women in clinical trials (20 % of CRT trial participants are women) [15–17], and a preponderance of non-ICM (NICM) among women in clinical trials [18]. Therefore, available data on CIED therapy in women with ICM is limited and largely based upon subgroup analyses. This review will focus on the ICD and CRT use in ischemic heart disease in women, with emphasis on prognosis, pathophysiology, and hypotheses for lower implantation rates among females. The interaction of women with NICM and CIED therapy has not been extensively discussed and is beyond the scope of this review.
* Nishaki Kiran Mehta [email protected] Melanie Maytin [email protected]
Review of Primary Prevention Trials
1
Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43220, USA
2
Division of Cardiovascular Medicine, 473 West 12th Avenue, Room 110P, Columbus, OH 43210-1252, USA
3
Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 70 Francis Street, Shapiro Center, Boston, MA 02115, USA
This assertion has been highly debated, with studies both supporting and contradicting sex disparities. Sex-based analyses from several primary prevention CIED trials (MADIT-II, Sudden Cardiac Death in Heart Failure (SCD-HeFT), the Defibrillators in Non-Ischemic Cardiom y o p a t h y Tr e a t m e n t E v a l u a t i o n ( D E F I N I T E ) )
33 Page 2 of 7
demonstrated no significant difference in survival between men and women with ICM and NICM, although there was a trend towards better outcomes among men [19–21]. The Registry to Improve the Use of EvidenceBased Heart Failure Therapies in the Outpatient Setting (IMPROVE-HF), a study to assess the efficacy of a heart failure quality improvement initiative applied in outpatient setting, reviewed the mortality outcomes in ICD/ CRT-D and CRT-D/CRT-P eligible and implanted outpatient populations over 2 years. They reported substantial and notably equal benefit between men and women for both groups. Given the previous finding of higher benefit with CRT-D in women [22••], the study investigators looked at the ICD-only group and established similar benefit for men and women. The analysis of device and sex interaction was not significant [11, 23••]. Unfortunately, women comprised only a fraction of the study populations (15–30 %) making it difficult to draw definitive conclusions. In contrast, several meta-analyses have suggested that ICD therapy for the primary prevention of SCD in women did not improve survival [10, 24, 25]. The question of whether a sex difference exists in ICD therapy remains unanswered. Currently available data are retrospective and underpowered with short duration of follow-up to detect if a divergence exists. Future, prospective randomized clinical ICD trials designed to include more women are needed. Current guidelines do not distinguish indications based upon sex [6]. Among the ICD recipients, women are less likely than men to receive appropriate ICD therapy, suggesting lower arrhythmic mortality among this group. Several studies have demonstrated a lower incidence of SCD and ventricular arrhythmias among women [26, 27]. This observation is consistent among the NICM and CRT-D subgroups also [28•].
Lower Arrhythmic Events in Women The Multicenter Unsustained Tachycardia Trial (MUSTT) was one of the first studies to report an arrhythmic sex disparity. On retrospective subgroup analysis, women had lower inducibility of ventricular tachycardia (VT) compared to men (24 vs. 36 %, p
WOMEN AND ISCHEMIC HEART DISEASE (M GULATI, SECTION EDITOR)
ICD and CRT Use in Ischemic Heart Disease in Women Nishaki Kiran Mehta 1 & William T. Abraham 2 & Melanie Maytin 3
Published online: 29 April 2015 # Springer Science+Business Media New York 2015
Abstract Although the role of implantable cardioverter defibrillator (ICD) and cardiac resynchronization therapy (CRT) in improving outcomes in ischemic cardiomyopathy (ICM) has been described, the data regarding gender-based survival outcomes are limited. There is a higher preponderance of nonischemic cardiomyopathy (NICM) in women, and most of the ICM literature is derived from sub-study analysis. This review summarizes the current body of literature on prognosis, pathophysiology, and the present clinical practice for device implantation in women with ICM. Keywords Cardiac resynchronization therapy . Gender differences . Implantable cardioverter defibrillator . Ischemic cardiomyopathy
Introduction The role of implantable cardioverter-defibrillator (ICD) and cardiac resynchronization therapy (CRT) is well established in improving clinical outcomes in patients with ischemic This article is part of the Topical Collection on Women and Ischemic Heart Disease
cardiomyopathy (ICM) [1–7]. The Multicenter Automatic Defibrillator Implantation Trial (MADIT II trial) is one of the several landmark trials that have demonstrated a marked mortality reduction in post-infarction patients with severely depressed left ventricular function [8]. Despite the demonstrated overall survival benefit with cardiac implantable electronic device (CIED) therapy, data regarding sex-based survival differences are limited. Studies have suggested that women tend to benefit less from primary prevention ICD therapy [9, 10] and, yet, derive more benefit from CRT, with echocardiographic evidence of reverse remodeling [11, 12••, 13, 14]. Whether these data are accurate remains to be understood. The major caveats that limit a complete understanding of the role of sex in ICM stem from: under-representation of women in clinical trials (20 % of CRT trial participants are women) [15–17], and a preponderance of non-ICM (NICM) among women in clinical trials [18]. Therefore, available data on CIED therapy in women with ICM is limited and largely based upon subgroup analyses. This review will focus on the ICD and CRT use in ischemic heart disease in women, with emphasis on prognosis, pathophysiology, and hypotheses for lower implantation rates among females. The interaction of women with NICM and CIED therapy has not been extensively discussed and is beyond the scope of this review.
* Nishaki Kiran Mehta [email protected] Melanie Maytin [email protected]
Review of Primary Prevention Trials
1
Division of Cardiovascular Medicine, The Ohio State University Wexner Medical Center, Columbus, OH 43220, USA
2
Division of Cardiovascular Medicine, 473 West 12th Avenue, Room 110P, Columbus, OH 43210-1252, USA
3
Division of Cardiovascular Medicine, Brigham and Women’s Hospital, 70 Francis Street, Shapiro Center, Boston, MA 02115, USA
This assertion has been highly debated, with studies both supporting and contradicting sex disparities. Sex-based analyses from several primary prevention CIED trials (MADIT-II, Sudden Cardiac Death in Heart Failure (SCD-HeFT), the Defibrillators in Non-Ischemic Cardiom y o p a t h y Tr e a t m e n t E v a l u a t i o n ( D E F I N I T E ) )
33 Page 2 of 7
demonstrated no significant difference in survival between men and women with ICM and NICM, although there was a trend towards better outcomes among men [19–21]. The Registry to Improve the Use of EvidenceBased Heart Failure Therapies in the Outpatient Setting (IMPROVE-HF), a study to assess the efficacy of a heart failure quality improvement initiative applied in outpatient setting, reviewed the mortality outcomes in ICD/ CRT-D and CRT-D/CRT-P eligible and implanted outpatient populations over 2 years. They reported substantial and notably equal benefit between men and women for both groups. Given the previous finding of higher benefit with CRT-D in women [22••], the study investigators looked at the ICD-only group and established similar benefit for men and women. The analysis of device and sex interaction was not significant [11, 23••]. Unfortunately, women comprised only a fraction of the study populations (15–30 %) making it difficult to draw definitive conclusions. In contrast, several meta-analyses have suggested that ICD therapy for the primary prevention of SCD in women did not improve survival [10, 24, 25]. The question of whether a sex difference exists in ICD therapy remains unanswered. Currently available data are retrospective and underpowered with short duration of follow-up to detect if a divergence exists. Future, prospective randomized clinical ICD trials designed to include more women are needed. Current guidelines do not distinguish indications based upon sex [6]. Among the ICD recipients, women are less likely than men to receive appropriate ICD therapy, suggesting lower arrhythmic mortality among this group. Several studies have demonstrated a lower incidence of SCD and ventricular arrhythmias among women [26, 27]. This observation is consistent among the NICM and CRT-D subgroups also [28•].
Lower Arrhythmic Events in Women The Multicenter Unsustained Tachycardia Trial (MUSTT) was one of the first studies to report an arrhythmic sex disparity. On retrospective subgroup analysis, women had lower inducibility of ventricular tachycardia (VT) compared to men (24 vs. 36 %, p
