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Effect of Coronary Artery Bypass Grafting on Left Ventricular Ejection Fraction in Men Eligible for Implantable Cardioverter–Defibrillator
Effect of Coronary Artery Bypass Grafting on Left Ventricular Ejection Fraction in Men Eligible for Implantable CardiovertereDefibrillator Kairav Vakil, MDa,b,*, Viorel Florea, MDa,b, Ryan Koene, MDb, Jessica Voight Kealhofer, MDb, Inderjit Anand, MD, D Phil (Oxon)c, and Selcuk Adabag, MD, MSa,b Implantable cardioverteredefibrillator (ICD) therapy for primary prevention of sudden cardiac death is not routinely recommended within 90 days of coronary artery bypass grafting (CABG) because of the possibility of an improvement in left ventricular ejection fraction (EF) to>35% after revascularization. We sought to determine the incidence and predictors of EF improvement to >35% after isolated CABG in patients who had a preoperative EF £35%. We studied 375 patients who underwent CABG at a tertiary institution and had an echocardiogram preoperatively and postoperatively. Of these, 74 patients (20%) with a preoperative EF £35% were included in this analysis. Improvement in EF was defined as postoperative EF >35%. In the overall study population (n [ 74), mean EF improved from 28 – 6% preoperatively to 36 – 12% postoperatively (p <0.0001). A total of 38 patients (51%) had postoperative improvement in EF to >35% (mean EF in these patients increased from 30 – 5% to 46 – 8%; p <0.0001). Patients with EF improvement had a higher preoperative EF than those with no improvement (30 – 5% vs 26 – 7%, p <0.005). Improvement in EF was 5 times more likely in patients with preoperative EF 26% to 35% (odds ratio 4.95, 95% CI 1.73 to 14.1; p [ 0.003) than those with preoperative EF £25%. Other clinical characteristics were not significantly different between patients with versus without EF improvement. In conclusion, more than half of the ICD-eligible patients who underwent CABG improved their EF to >35% after surgery and became ineligible for a primary prevention ICD. EF improvement was unlikely in patients with preoperative EF <25%. Published by Elsevier Inc. (Am J Cardiol 2016;117:957e960) Implantable cardioverteredefibrillator (ICD) therapy for primary prevention of sudden cardiac death (SCD) is not routinely recommended within 90 days of coronary artery bypass grafting (CABG).1 Instead, it is recommended that patients with preoperative ejection fraction (EF) 35% undergo a reassessment of left ventricular (LV) systolic function 90 days after CABG to assess improvement in EF after revascularization.2 Although it may be reasonable to expect that elimination of ischemia and recovery of hibernating myocardium might improve LV systolic function,3 the actual evidence that EF improves after CABG and exceeds 35%, obviating implantation of an ICD, is sparse. To address this question, we examined the incidence and predictors of improvement in LV EF to >35% after isolated CABG in patients who were otherwise eligible for primary prevention ICD implantation based on a preoperative EF of 35%.
a Division of Cardiology, Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota; bDivision of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota; and cDivision of Cardiology, Department of Medicine, Veterans Affairs Medical Center, San Diego, California. Manuscript received September 14, 2015; revised manuscript received and accepted December 17, 2015. Drs. Vakil and Floreahave equally contributed to the manuscript. See page 959 for disclosure information. *Corresponding author: Tel: (612) 467-3662; fax: (612) 727-5668. E-mail address: [email protected] (K. Vakil).
0002-9149/16/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjcard.2015.12.029
Methods A total of 2,838 patients underwent isolated CABG at the Minneapolis Veterans Affairs Health Care System from January 1, 2001, to December 31, 2014, and were recorded in our cardiac surgery database.4e6 In 375 of these patients, an echocardiogram was performed preoperatively (within 6 months) and postoperatively (within 3 to 24 months) based on clinical indications. Of these 375 patients, we examined 74 patients (20%) who had a preoperative LV EF 35%. This study was approved by the Institutional Review Board at the Minneapolis Veterans Affairs Health Care System. The 2-dimensional echocardiograms were performed by experienced cardiac sonographers and interpreted by boardcertified cardiologists experienced in echocardiography. In addition to visual estimation, LV EF was calculated based on the American Society of Echocardiography guidelines for EF quantification.7 Improvement in LV function was defined as an increase in LV EF to >35% after revascularization. Continuous and categorical variables are summarized as mean SD and frequency (%), respectively. We compared the baseline characteristics of patients with improved postoperative EF (>35%) versus those with unchanged postoperative EF (35%) using t test for continuous variables that were normally distributed and ManneWhitney U test for continuous variables that were non normally distributed. For categorical variables, we used the chi-square test and Fisher’s exact test. We used logistic regression analysis to examine www.ajconline.org
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The American Journal of Cardiology (www.ajconline.org)
Table 1 Baseline characteristics of study patients in relation to perioperative change in left ventricular ejection fraction Variable
All Ejection Fraction p-value patients n¼74 Improved Unchanged (>35%) (35%) n¼38 n¼ 36
Age (years) Men Preoperative left ventricular ejection fraction Prior myocardial infarction Hypertension Diabetes mellitus Atrial fibrillation Chronic kidney disease stage 3 Obstructive lung disease Prior stroke Peripheral arterial disease Prior cardiac surgery Laboratory Values Glomerular filtration rate (ml/min/1.73m2) Hemoglobin (g/dL) Perfusion Imaging Infarction Ischemia Viability Medications Beta blocker ACE-inhibitors or Angiotensin receptor blockers Spironolactone Hydralazine and ISDN Digoxin Diuretics Operative Parameters Number of grafts Arterial grafts Complete revascularization Bypass time (minutes) Ischemic time (minutes)
659 100% 286%
659 100% 305%
659 100% 267%
0.97 1.00 <0.005
85% 82% 28% 10% 22% 39% 24% 45% 5%
82% 84% 24% 11% 16% 40% 21% 42% 3%
89% 81% 33% 8% 28% 39% 28% 47% 8%
0.52 0.77 0.36 1.00 0.26 0.96 0.50 0.66 0.35
8631
9233
8027
0.09
13.61.8 13.71.9 13.61.7
0.97
64% 56% 52%
61% 67% 50%
67% 40% 54%
0.69 0.21 0.86
95% 81%
97% 89%
94% 75%
0.62 0.14
18% 10% 20% 66%
14% 8% 19% 60%
22% 11% 22% 75%
0.37 0.71 0.73 0.16
2.90.8 92% 85% 12343 7528
3.00.7 100% 90% 12329 7819
2.80.9 83% 81% 12455 7135
0.47 0.01 0.28 0.88 0.30
Table 2 Magnitude of change in left ventricular ejection fraction post revascularization Variable All patients (n¼74) Ejection fraction improved to >35% (n¼38) Unchanged ejection fraction 35% (n¼36)
Figure 1. Distribution of preoperative and postoperative EF in the overall study cohort (n ¼ 74) and the subgroups with improved (n ¼ 38) and unchanged (n ¼ 36) EF.
Preoperative Postoperative p-value ejection fraction ejection fraction 286% 305%
3612% 468%
<0.0001 <0.0001
267%
267%
0.91
the variables associated with perioperative improvement in EF. We compared the changes in preoperative versus postoperative echocardiographic parameters with paired t test. All p values were 2-sided with a significance of <0.05. Analyses were performed using SPSS, version 19.0 (IBM Corp, Armonk, New York).
Figure 2. Likelihood of EF improvement after surgery in relation to preoperative EF.
Results Mean age of the 74 patients included in the analysis was 65 9 years. Mean preoperative EF was 28 6% (range 15% to 35%). A total of 63 patients (85%) had a history of myocardial infarction. Patients were on excellent medical therapy for heart failure with reduced EF; with 95% taking a b blocker and 81% taking either an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker. Baseline characteristics of the study patients are presented in Table 1. In the overall study population, mean EF improved from 28 6% (range 15% to 35%) preoperatively to 36 12% (range 10% to 65%) postoperatively (p <0.0001; Table 2; Figure 1). Thirty-eight patients (51%) had postoperative improvement in EF to >35%. In these 38 patients, the mean LV EF increased from 30 5% to 46 8% (p <0.0001; Table 2; Figure 1). In the other 36 patients (49%), the EF remained unchanged after CABG (26 7% vs 26 7%; p ¼ 0.91). Patients who improved their EF to >35% postoperatively had a higher preoperative EF than those who did not improve their EF to >35% (30 5% vs 26 7%, p <0.005). Improvement in EF to >35% postoperatively was more likely in patients with a preoperative EF of 26% to 35% (n ¼ 48) than those with EF 25% (65% vs 27%, p ¼ 0.002; Figure 2). Consequently, patients with a
Heart Failure/CABG-Related Improvement in LV EF
preoperative EF of 26% to 35% were 5 times more likely to improve their EF to >35% after CABG (odds ratio 4.95, 95% CI 1.73 to 14.1; p ¼ 0.003) than those with a preoperative EF 25%. A total of 44 patients had myocardial perfusion imaging or viability study. Infarct, ischemia, viability, and other clinical characteristics were not significantly different between patients with versus without improvement in EF after CABG (Table 1). Discussion This study showed that approximately 50% of the ICDeligible patients who underwent CABG with a preoperative EF 35% improved their EF to >35% after CABG and were no longer candidates for an ICD for primary prevention of SCD. Improvement in EF to >35% was 5 times more likely in patients with a preoperative EF of 26% to 35% compared to those with a preoperative EF 25%. Although these results support the current practice guideline recommendation of reassessing EF 90 days after CABG in ICDeligible patients, they also suggest that it is less likely for patients with a preoperative EF 25% to become ineligible for a primary prevention ICD after CABG. Although CABG is a widely available and a frequently performed surgical procedure, little is known about the evolution of LV EF perioperatively. In part, this is because follow-up echocardiograms are not routinely performed after CABG unless indicated by clinical circumstances. Previously, in relatively small case series of patients with LV systolic dysfunction, revascularization was associated with a significant improvement in LV EF.8,9 Elefteriades et al9 studied 83 patients with a preoperative EF <30% and found that the mean EF improved from 25% preoperatively to 33% postoperatively. Similarly, in patients with EF <50% undergoing CABG, Cornel et al8 reported that mean EF improved from 32% to 42%. Similar results were noted in a subgroup analysis of the Surgical Treatment for Ischemic Heart Failure trial, which showed a significant improvement in LV size after revascularization in patients that had severely dilated LV preoperatively.10,11 However, none of the previous studies have used a 35% cut-off point in EF to assess the impact of revascularization with CABG on ICD eligibility. Thus, the results of the present study provide novel information within this context. Previously, in subgroup analyses of major ICD trials, patients who underwent coronary artery revascularization within 6 to 18 months before ICD implantation did not benefit from device implantation.12e14 Furthermore, in the CABG-Patch trial, where patients with LV EF of 35% and abnormal signal average electrocardiogram were randomly assigned to ICD versus medical therapy at the time of CABG, there was no difference in mortality between the 2 treatment groups.15 Perhaps, one possible explanation for the absence of mortality benefit with ICD in CABG-Patch trial may be the perioperative improvement in LV function in some patients. The results of the present study support such a hypothesis. Although ICD therapy for primary prevention of SCD is currently limited to patients with EF 35%, there is some evidence that patients with EF >35% may also benefit. Studying patients with an existing ICD for primary
959
prevention of SCD, Naksuk et al,16 and Kini et al17 found that 27% and 26% of ICD patients had improvement of EF to >35% at the time of generator replacement. Despite that, after generator replacement, the risk of appropriate ICD shocks in patients with improved EF was similar to those with unchanged EF in the study by Naksuk et al,16 and lower, but not negligible, in the study by Kini et al.17 Thus, improvement in EF to >35% may not necessarily be synonymous with abolishment of SCD risk.18,19 This study has the disadvantages of being retrospective and uncontrolled and is thus hypothesis-generating, rather than definitive. Because echocardiograms were not routinely obtained after CABG, this could have introduced a selection bias in our patient sample. Echocardiographic measurements in individual patients were made on only 2 occasions. Thus, we cannot say whether the changes in EF remained consistent in the longer term. Furthermore, the pre-CABG and post-CABG echocardiograms were not performed at predefined time points and were not reinterpreted for the purposes of this study. Thus, some of the changes in EF could be due to interreader variability. Finally, the study was carried out at the Minneapolis Veterans Affairs Medical Center and was therefore limited to men only. Disclosures The authors have no conflicts of interest to disclose. 1. Kusumoto FM, Calkins H, Boehmer J, Buxton AE, Chung MK, Gold MR, Hohnloser SH, Indik J, Lee R, Mehra MR, Menon V, Page RL, Shen WK, Slotwiner DJ, Warner Stevenson L, Varosy PD, Welikovitch L. HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. Heart Rhythm 2014;11:1271e1303. 2. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51: e1ee62. 3. Colbert RW, Holley CT, Stone LH, Crampton M, Adabag S, Garcia S, Iaizzo PA, Ward HB, Kelly RF, McFalls EO. The Recovery of Hibernating Hearts Lies on a Spectrum: from Bears in Nature to Patients with Coronary Artery Disease. J Cardiovasc Transl Res 2015;8:244e252. 4. Garcia S, Ko B, Adabag S. Contrast-induced nephropathy and risk of acute kidney injury and mortality after cardiac operations. Ann Thorac Surg 2012;94:772e776. 5. Jain R, Duval S, Adabag S. How accurate is the eyeball test?: a comparison of physician’s subjective assessment versus statistical methods in estimating mortality risk after cardiac surgery. Circ Cardiovasc Qual Outcomes 2014;7:151e156. 6. Raza SS, Li JM, John R, Chen LY, Tholakanahalli VN, Mbai M, Adabag AS. Long-term mortality and pacing outcomes of patients with permanent pacemaker implantation after cardiac surgery. Pacing Clin Electrophysiol 2011;34:331e338.
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7. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440e1463. 8. Cornel JH, Bax JJ, Elhendy A, Maat AP, Kimman GJ, Geleijnse ML, Rambaldi R, Boersma E, Fioretti PM. Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy. J Am Coll Cardiol 1998;31:1002e1010. 9. Elefteriades JA, Tolis G Jr, Levi E, Mills LK, Zaret BL. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol 1993;22:1411e1417. 10. Michler RE, Rouleau JL, Al-Khalidi HR, Bonow RO, Pellikka PA, Pohost GM, Holly TA, Oh JK, Dagenais F, Milano C, Wrobel K, Pirk J, Ali IS, Jones RH, Velazquez EJ, Lee KL, Di Donato M; STICH Trial Investigators. Insights from the STICH trial: change in left ventricular size after coronary artery bypass grafting with and without surgical ventricular reconstruction. J Thorac Cardiovasc Surg 2013;146: 1139e1145 e1136. 11. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, Ali IS, Pohost G, Gradinac S, Abraham WT, Yii M, Prabhakaran D, Szwed H, Ferrazzi P, Petrie MC, O’Connor CM, Panchavinnin P, She L, Bonow RO, Rankin GR, Jones RH, Rouleau JL; STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607e1616.
12. Barsheshet A, Goldenberg I, Moss AJ, Huang DT, Zareba W, McNitt S, Klein HU, Guetta V. Effect of elapsed time from coronary revascularization to implantation of a cardioverter defibrillator on long-term survival in the MADIT-II trial. J Cardiovasc Electrophysiol 2011;22: 1237e1242. 13. Barsheshet A, Goldenberg I, Narins CR, Moss AJ, McNitt S, Wang PJ, Huang DT, Hall WJ, Zareba W, Eldar M, Guetta V. Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm 2010;7:1421e1427. 14. Goldenberg I, Moss AJ, McNitt S, Zareba W, Hall WJ, Andrews ML, Wilber DJ, Klein HU; MADIT II Investigators. Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol 2006;47:1811e1817. 15. Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997;337:1569e1575. 16. Naksuk N, Saab A, Li JM, Florea V, Akkaya M, Anand IS, Benditt DG, Adabag S. Incidence of appropriate shock in implantable cardioverter-defibrillator patients with improved ejection fraction. J Card Fail 2013;19:426e430. 17. Kini V, Soufi MK, Deo R, Epstein AE, Bala R, Riley M, Groeneveld PW, Shalaby A, Dixit S. Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met? J Am Coll Cardiol 2014;63: 2388e2394. 18. Adabag S, Smith LG, Anand IS, Berger AK, Luepker RV. Sudden cardiac death in heart failure patients with preserved ejection fraction. J Card Fail 2012;18:749e754. 19. Adabag S, Rector TS, Anand IS, McMurray JJ, Zile M, Komajda M, McKelvie RS, Massie B, Carson PE. A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 2014;16:1175e1182.
a Division of Cardiology, Department of Medicine, Veterans Affairs Medical Center, Minneapolis, Minnesota; bDivision of Cardiology, Department of Medicine, University of Minnesota, Minneapolis, Minnesota; and cDivision of Cardiology, Department of Medicine, Veterans Affairs Medical Center, San Diego, California. Manuscript received September 14, 2015; revised manuscript received and accepted December 17, 2015. Drs. Vakil and Floreahave equally contributed to the manuscript. See page 959 for disclosure information. *Corresponding author: Tel: (612) 467-3662; fax: (612) 727-5668. E-mail address: [email protected] (K. Vakil).
0002-9149/16/$ - see front matter Published by Elsevier Inc. http://dx.doi.org/10.1016/j.amjcard.2015.12.029
Methods A total of 2,838 patients underwent isolated CABG at the Minneapolis Veterans Affairs Health Care System from January 1, 2001, to December 31, 2014, and were recorded in our cardiac surgery database.4e6 In 375 of these patients, an echocardiogram was performed preoperatively (within 6 months) and postoperatively (within 3 to 24 months) based on clinical indications. Of these 375 patients, we examined 74 patients (20%) who had a preoperative LV EF 35%. This study was approved by the Institutional Review Board at the Minneapolis Veterans Affairs Health Care System. The 2-dimensional echocardiograms were performed by experienced cardiac sonographers and interpreted by boardcertified cardiologists experienced in echocardiography. In addition to visual estimation, LV EF was calculated based on the American Society of Echocardiography guidelines for EF quantification.7 Improvement in LV function was defined as an increase in LV EF to >35% after revascularization. Continuous and categorical variables are summarized as mean SD and frequency (%), respectively. We compared the baseline characteristics of patients with improved postoperative EF (>35%) versus those with unchanged postoperative EF (35%) using t test for continuous variables that were normally distributed and ManneWhitney U test for continuous variables that were non normally distributed. For categorical variables, we used the chi-square test and Fisher’s exact test. We used logistic regression analysis to examine www.ajconline.org
958
The American Journal of Cardiology (www.ajconline.org)
Table 1 Baseline characteristics of study patients in relation to perioperative change in left ventricular ejection fraction Variable
All Ejection Fraction p-value patients n¼74 Improved Unchanged (>35%) (35%) n¼38 n¼ 36
Age (years) Men Preoperative left ventricular ejection fraction Prior myocardial infarction Hypertension Diabetes mellitus Atrial fibrillation Chronic kidney disease stage 3 Obstructive lung disease Prior stroke Peripheral arterial disease Prior cardiac surgery Laboratory Values Glomerular filtration rate (ml/min/1.73m2) Hemoglobin (g/dL) Perfusion Imaging Infarction Ischemia Viability Medications Beta blocker ACE-inhibitors or Angiotensin receptor blockers Spironolactone Hydralazine and ISDN Digoxin Diuretics Operative Parameters Number of grafts Arterial grafts Complete revascularization Bypass time (minutes) Ischemic time (minutes)
659 100% 286%
659 100% 305%
659 100% 267%
0.97 1.00 <0.005
85% 82% 28% 10% 22% 39% 24% 45% 5%
82% 84% 24% 11% 16% 40% 21% 42% 3%
89% 81% 33% 8% 28% 39% 28% 47% 8%
0.52 0.77 0.36 1.00 0.26 0.96 0.50 0.66 0.35
8631
9233
8027
0.09
13.61.8 13.71.9 13.61.7
0.97
64% 56% 52%
61% 67% 50%
67% 40% 54%
0.69 0.21 0.86
95% 81%
97% 89%
94% 75%
0.62 0.14
18% 10% 20% 66%
14% 8% 19% 60%
22% 11% 22% 75%
0.37 0.71 0.73 0.16
2.90.8 92% 85% 12343 7528
3.00.7 100% 90% 12329 7819
2.80.9 83% 81% 12455 7135
0.47 0.01 0.28 0.88 0.30
Table 2 Magnitude of change in left ventricular ejection fraction post revascularization Variable All patients (n¼74) Ejection fraction improved to >35% (n¼38) Unchanged ejection fraction 35% (n¼36)
Figure 1. Distribution of preoperative and postoperative EF in the overall study cohort (n ¼ 74) and the subgroups with improved (n ¼ 38) and unchanged (n ¼ 36) EF.
Preoperative Postoperative p-value ejection fraction ejection fraction 286% 305%
3612% 468%
<0.0001 <0.0001
267%
267%
0.91
the variables associated with perioperative improvement in EF. We compared the changes in preoperative versus postoperative echocardiographic parameters with paired t test. All p values were 2-sided with a significance of <0.05. Analyses were performed using SPSS, version 19.0 (IBM Corp, Armonk, New York).
Figure 2. Likelihood of EF improvement after surgery in relation to preoperative EF.
Results Mean age of the 74 patients included in the analysis was 65 9 years. Mean preoperative EF was 28 6% (range 15% to 35%). A total of 63 patients (85%) had a history of myocardial infarction. Patients were on excellent medical therapy for heart failure with reduced EF; with 95% taking a b blocker and 81% taking either an angiotensin-converting enzyme inhibitor or angiotensin-II receptor blocker. Baseline characteristics of the study patients are presented in Table 1. In the overall study population, mean EF improved from 28 6% (range 15% to 35%) preoperatively to 36 12% (range 10% to 65%) postoperatively (p <0.0001; Table 2; Figure 1). Thirty-eight patients (51%) had postoperative improvement in EF to >35%. In these 38 patients, the mean LV EF increased from 30 5% to 46 8% (p <0.0001; Table 2; Figure 1). In the other 36 patients (49%), the EF remained unchanged after CABG (26 7% vs 26 7%; p ¼ 0.91). Patients who improved their EF to >35% postoperatively had a higher preoperative EF than those who did not improve their EF to >35% (30 5% vs 26 7%, p <0.005). Improvement in EF to >35% postoperatively was more likely in patients with a preoperative EF of 26% to 35% (n ¼ 48) than those with EF 25% (65% vs 27%, p ¼ 0.002; Figure 2). Consequently, patients with a
Heart Failure/CABG-Related Improvement in LV EF
preoperative EF of 26% to 35% were 5 times more likely to improve their EF to >35% after CABG (odds ratio 4.95, 95% CI 1.73 to 14.1; p ¼ 0.003) than those with a preoperative EF 25%. A total of 44 patients had myocardial perfusion imaging or viability study. Infarct, ischemia, viability, and other clinical characteristics were not significantly different between patients with versus without improvement in EF after CABG (Table 1). Discussion This study showed that approximately 50% of the ICDeligible patients who underwent CABG with a preoperative EF 35% improved their EF to >35% after CABG and were no longer candidates for an ICD for primary prevention of SCD. Improvement in EF to >35% was 5 times more likely in patients with a preoperative EF of 26% to 35% compared to those with a preoperative EF 25%. Although these results support the current practice guideline recommendation of reassessing EF 90 days after CABG in ICDeligible patients, they also suggest that it is less likely for patients with a preoperative EF 25% to become ineligible for a primary prevention ICD after CABG. Although CABG is a widely available and a frequently performed surgical procedure, little is known about the evolution of LV EF perioperatively. In part, this is because follow-up echocardiograms are not routinely performed after CABG unless indicated by clinical circumstances. Previously, in relatively small case series of patients with LV systolic dysfunction, revascularization was associated with a significant improvement in LV EF.8,9 Elefteriades et al9 studied 83 patients with a preoperative EF <30% and found that the mean EF improved from 25% preoperatively to 33% postoperatively. Similarly, in patients with EF <50% undergoing CABG, Cornel et al8 reported that mean EF improved from 32% to 42%. Similar results were noted in a subgroup analysis of the Surgical Treatment for Ischemic Heart Failure trial, which showed a significant improvement in LV size after revascularization in patients that had severely dilated LV preoperatively.10,11 However, none of the previous studies have used a 35% cut-off point in EF to assess the impact of revascularization with CABG on ICD eligibility. Thus, the results of the present study provide novel information within this context. Previously, in subgroup analyses of major ICD trials, patients who underwent coronary artery revascularization within 6 to 18 months before ICD implantation did not benefit from device implantation.12e14 Furthermore, in the CABG-Patch trial, where patients with LV EF of 35% and abnormal signal average electrocardiogram were randomly assigned to ICD versus medical therapy at the time of CABG, there was no difference in mortality between the 2 treatment groups.15 Perhaps, one possible explanation for the absence of mortality benefit with ICD in CABG-Patch trial may be the perioperative improvement in LV function in some patients. The results of the present study support such a hypothesis. Although ICD therapy for primary prevention of SCD is currently limited to patients with EF 35%, there is some evidence that patients with EF >35% may also benefit. Studying patients with an existing ICD for primary
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prevention of SCD, Naksuk et al,16 and Kini et al17 found that 27% and 26% of ICD patients had improvement of EF to >35% at the time of generator replacement. Despite that, after generator replacement, the risk of appropriate ICD shocks in patients with improved EF was similar to those with unchanged EF in the study by Naksuk et al,16 and lower, but not negligible, in the study by Kini et al.17 Thus, improvement in EF to >35% may not necessarily be synonymous with abolishment of SCD risk.18,19 This study has the disadvantages of being retrospective and uncontrolled and is thus hypothesis-generating, rather than definitive. Because echocardiograms were not routinely obtained after CABG, this could have introduced a selection bias in our patient sample. Echocardiographic measurements in individual patients were made on only 2 occasions. Thus, we cannot say whether the changes in EF remained consistent in the longer term. Furthermore, the pre-CABG and post-CABG echocardiograms were not performed at predefined time points and were not reinterpreted for the purposes of this study. Thus, some of the changes in EF could be due to interreader variability. Finally, the study was carried out at the Minneapolis Veterans Affairs Medical Center and was therefore limited to men only. Disclosures The authors have no conflicts of interest to disclose. 1. Kusumoto FM, Calkins H, Boehmer J, Buxton AE, Chung MK, Gold MR, Hohnloser SH, Indik J, Lee R, Mehra MR, Menon V, Page RL, Shen WK, Slotwiner DJ, Warner Stevenson L, Varosy PD, Welikovitch L. HRS/ACC/AHA expert consensus statement on the use of implantable cardioverter-defibrillator therapy in patients who are not included or not well represented in clinical trials. Heart Rhythm 2014;11:1271e1303. 2. Epstein AE, DiMarco JP, Ellenbogen KA, Estes NA 3rd, Freedman RA, Gettes LS, Gillinov AM, Gregoratos G, Hammill SC, Hayes DL, Hlatky MA, Newby LK, Page RL, Schoenfeld MH, Silka MJ, Stevenson LW, Sweeney MO, Smith SC Jr, Jacobs AK, Adams CD, Anderson JL, Buller CE, Creager MA, Ettinger SM, Faxon DP, Halperin JL, Hiratzka LF, Hunt SA, Krumholz HM, Kushner FG, Lytle BW, Nishimura RA, Ornato JP, Page RL, Riegel B, Tarkington LG, Yancy CW; American College of Cardiology/American Heart Association Task Force on Practice Guidelines; American Association for Thoracic Surgery; Society of Thoracic Surgeons. ACC/AHA/HRS 2008 guidelines for device-based therapy of cardiac rhythm abnormalities: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (writing committee to revise the ACC/AHA/NASPE 2002 guideline update for implantation of cardiac pacemakers and antiarrhythmia devices) developed in collaboration with the American Association for Thoracic Surgery and Society of Thoracic Surgeons. J Am Coll Cardiol 2008;51: e1ee62. 3. Colbert RW, Holley CT, Stone LH, Crampton M, Adabag S, Garcia S, Iaizzo PA, Ward HB, Kelly RF, McFalls EO. The Recovery of Hibernating Hearts Lies on a Spectrum: from Bears in Nature to Patients with Coronary Artery Disease. J Cardiovasc Transl Res 2015;8:244e252. 4. Garcia S, Ko B, Adabag S. Contrast-induced nephropathy and risk of acute kidney injury and mortality after cardiac operations. Ann Thorac Surg 2012;94:772e776. 5. Jain R, Duval S, Adabag S. How accurate is the eyeball test?: a comparison of physician’s subjective assessment versus statistical methods in estimating mortality risk after cardiac surgery. Circ Cardiovasc Qual Outcomes 2014;7:151e156. 6. Raza SS, Li JM, John R, Chen LY, Tholakanahalli VN, Mbai M, Adabag AS. Long-term mortality and pacing outcomes of patients with permanent pacemaker implantation after cardiac surgery. Pacing Clin Electrophysiol 2011;34:331e338.
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7. Lang RM, Bierig M, Devereux RB, Flachskampf FA, Foster E, Pellikka PA, Picard MH, Roman MJ, Seward J, Shanewise JS, Solomon SD, Spencer KT, Sutton MS, Stewart WJ; Chamber Quantification Writing Group; American Society of Echocardiography’s Guidelines and Standards Committee; European Association of Echocardiography. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr 2005;18:1440e1463. 8. Cornel JH, Bax JJ, Elhendy A, Maat AP, Kimman GJ, Geleijnse ML, Rambaldi R, Boersma E, Fioretti PM. Biphasic response to dobutamine predicts improvement of global left ventricular function after surgical revascularization in patients with stable coronary artery disease: implications of time course of recovery on diagnostic accuracy. J Am Coll Cardiol 1998;31:1002e1010. 9. Elefteriades JA, Tolis G Jr, Levi E, Mills LK, Zaret BL. Coronary artery bypass grafting in severe left ventricular dysfunction: excellent survival with improved ejection fraction and functional state. J Am Coll Cardiol 1993;22:1411e1417. 10. Michler RE, Rouleau JL, Al-Khalidi HR, Bonow RO, Pellikka PA, Pohost GM, Holly TA, Oh JK, Dagenais F, Milano C, Wrobel K, Pirk J, Ali IS, Jones RH, Velazquez EJ, Lee KL, Di Donato M; STICH Trial Investigators. Insights from the STICH trial: change in left ventricular size after coronary artery bypass grafting with and without surgical ventricular reconstruction. J Thorac Cardiovasc Surg 2013;146: 1139e1145 e1136. 11. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, Ali IS, Pohost G, Gradinac S, Abraham WT, Yii M, Prabhakaran D, Szwed H, Ferrazzi P, Petrie MC, O’Connor CM, Panchavinnin P, She L, Bonow RO, Rankin GR, Jones RH, Rouleau JL; STICH Investigators. Coronary-artery bypass surgery in patients with left ventricular dysfunction. N Engl J Med 2011;364:1607e1616.
12. Barsheshet A, Goldenberg I, Moss AJ, Huang DT, Zareba W, McNitt S, Klein HU, Guetta V. Effect of elapsed time from coronary revascularization to implantation of a cardioverter defibrillator on long-term survival in the MADIT-II trial. J Cardiovasc Electrophysiol 2011;22: 1237e1242. 13. Barsheshet A, Goldenberg I, Narins CR, Moss AJ, McNitt S, Wang PJ, Huang DT, Hall WJ, Zareba W, Eldar M, Guetta V. Time dependence of life-threatening ventricular tachyarrhythmias after coronary revascularization in MADIT-CRT. Heart Rhythm 2010;7:1421e1427. 14. Goldenberg I, Moss AJ, McNitt S, Zareba W, Hall WJ, Andrews ML, Wilber DJ, Klein HU; MADIT II Investigators. Time dependence of defibrillator benefit after coronary revascularization in the Multicenter Automatic Defibrillator Implantation Trial (MADIT)-II. J Am Coll Cardiol 2006;47:1811e1817. 15. Bigger JT Jr. Prophylactic use of implanted cardiac defibrillators in patients at high risk for ventricular arrhythmias after coronary-artery bypass graft surgery. Coronary Artery Bypass Graft (CABG) Patch Trial Investigators. N Engl J Med 1997;337:1569e1575. 16. Naksuk N, Saab A, Li JM, Florea V, Akkaya M, Anand IS, Benditt DG, Adabag S. Incidence of appropriate shock in implantable cardioverter-defibrillator patients with improved ejection fraction. J Card Fail 2013;19:426e430. 17. Kini V, Soufi MK, Deo R, Epstein AE, Bala R, Riley M, Groeneveld PW, Shalaby A, Dixit S. Appropriateness of primary prevention implantable cardioverter-defibrillators at the time of generator replacement: are indications still met? J Am Coll Cardiol 2014;63: 2388e2394. 18. Adabag S, Smith LG, Anand IS, Berger AK, Luepker RV. Sudden cardiac death in heart failure patients with preserved ejection fraction. J Card Fail 2012;18:749e754. 19. Adabag S, Rector TS, Anand IS, McMurray JJ, Zile M, Komajda M, McKelvie RS, Massie B, Carson PE. A prediction model for sudden cardiac death in patients with heart failure and preserved ejection fraction. Eur J Heart Fail 2014;16:1175e1182.