|Year : 2017 | Volume
| Issue : 2 | Page : 68-73
Ischemic cardiomyopathy is an independent predictor of mortality in patients presenting for Heart Mate II left ventricular assist device implantation
Sanjay Kumar1, Charisse Ward2, Lynn Wilson2, Abeel A Mangi2
1 Department of Cardiothoracic Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi, Uttar Pradesh, India; Division of Cardiac Surgery, Yale University Medical Centre, New Haven, CT, USA
2 Division of Cardiac Surgery, Yale University Medical Centre, New Haven, CT, USA
|Date of Web Publication||20-Jun-2017|
Department of Cardiovascular and Thoracic Surgery, Institute of Medical Sciences, Banaras Hindu University, Varanasi - 221 005, Uttar Pradesh
Source of Support: None, Conflict of Interest: None
Objective: No clinical study compares outcomes of left ventricular assist device (LVAD) implantation in patients with end-stage heart failure secondary to ischemic cardiomyopathy (ICM) and non-ICM (NICM). The purpose of this study is to analyze the outcome of LVAD therapy in these 2 cohorts of patients.
Materials and Methods: Forty-four patients had HeartMate II LVAD implantation between September 2012 and August 2014. Charts were retrospectively reviewed and data accumulated were statistically analyzed.
Results: A total of 23 (52%) patients were presented with ICM. Average age in ICM was 63.7 ± 6.8 years as opposed to 53.9 ± 16.3 in NICM (P = 0.017). About 78% of ICM and 67% of NICM group were male (P = 0.388). 43.5% of ICM had undergone previous cardiac operation versus 9.5% of NICM (P = 0.012). Implant strategy was bridge to transplant in 78% of ICM and 67% of NICM (P = NS) and destination therapy in 22% of ICM and 33% of NICM (P = NS). A thirty-day mortality rate was 17% in the ICM and 0% in the NICM (P = 0.06). One-year mortality was 39% for ICM and 19% for NICM (P = 0.14). On multivariate analysis, ICM emerged as an independent predictor of mortality (odds ratio: 3.19). Variables such as serum creatinine, inotropic or vasopressor requirement, intraaortic balloon pump use, or complex operations involving aortic or tricuspid valves at the time of LVAD placement did not impact mortality.
Conclusions: This report, based on a nonmatched cohort of 44 patients, demonstrates that in an era of selective criteria for LVAD implantation, ICM emerges as an independent predictor of mortality. These patients tend to be older and are more likely to be undergoing reoperative sternotomy. These results should form the basis for a larger scale investigation of LVAD implantation in ICM patients.
Keywords: Cardiomyopathy, HeartMate II, ischemic cardiomyopathy, left ventricular assist device
|How to cite this article:|
Kumar S, Ward C, Wilson L, Mangi AA. Ischemic cardiomyopathy is an independent predictor of mortality in patients presenting for Heart Mate II left ventricular assist device implantation. Heart India 2017;5:68-73
|How to cite this URL:|
Kumar S, Ward C, Wilson L, Mangi AA. Ischemic cardiomyopathy is an independent predictor of mortality in patients presenting for Heart Mate II left ventricular assist device implantation. Heart India [serial online] 2017 [cited 2017 Aug 16];5:68-73. Available from: http://www.heartindia.net/text.asp?2017/5/2/68/208550
| Introduction|| |
Multiple trials and epidemiologic surveys have shown that ischemic cardiomyopathy (ICM) has decreased survival compared to patients with nonischemic dilated cardiomyopathy (NIDCM). Increased age, multivessel arteriopathy, potent neurohormonal stimulation, and arrhythmias associated with sudden death predispose patients with ICM to greater morbidity and mortality compared to patients with NIDCM.
Myocardial response to left ventricular assist device (LVAD) therapy has been of particular interest. Left ventricular (LV) unloading is characterized by changes in proteomic expression with subsequent improvement in contractile functions of cardiomyocytes, normalization of LV geometry, and neurohormonal function, a process termed reverse remodeling. These changes are more likely to occur in the dysfunctional, yet viable, myocardium of patients with NIDCM.,,
Observed improvement in LV function with LVAD therapy led to patients being explanted. Unfortunately, myocardial recovery at cellular and molecular level has not been associated with analogous bridge to recovery rates.,
The effect that heart failure etiology may have on patients with continuous-flow LVADs as a bridge to transplantation (BTT) or destination therapy (DT) has not been fully investigated.
The term NIDCM includes various subtypes of cardiomyopathy including idiopathic dilated, hypertrophic, restrictive, postpartum, and viral. From this group of NIDCM, LVADs at our institution were only implanted for idiopathic dilated cardiomyopathy (IDCM).
So far, no clinical study systematically compares outcomes of HeartMate II LVAD implantation in patients with end-stage heart failure secondary to ICM and non-ICM (NICM). The purpose of this study is to analyze the outcomes following continuous-flow LVAD implantation in these 2 cohorts of patients.
| Materials and Methods|| |
The Institutional Review Board approved this retrospective study. We retrospectively reviewed our institutions' LVAD dataset and analyzed patients who underwent continuous-flow LVAD implantation as a BTT or a DT from September 2012 to August 2014. A total of 44 patients were identified and formed the cohort of this study.
Patients were stratified into two groups (ICM and NIDCM) based on the etiology of heart failure. Stratification of ICM versus NIDCM was based on a history of angina or myocardial infarction, coronary angiography findings, and echocardiography results.
Forty-four patients had received HeartMate II LVAD implantation (Thoratec Corp., Pleasanton, CA, USA) between September 2012 and August 2014. Data accumulated were statistically analyzed.
Patient's demographics included age, gender, race, body surface area, body mass index (BMI), previous sternotomy, days in hospital before LVAD implantation, preoperative creatinine, liver function tests, and associated comorbidities, for example, hypertension, diabetes mellitus, chronic renal insufficiency (CRI), dialysis, chronic obstructive pulmonary disease, and peripheral vascular disease. CRI was defined as glomerular filtration rate <60 ml/min/m 2.
Operative characteristics analyzed were cardiopulmonary bypass time and indication (BTT or DT). Hemodynamic and echocardiographic data included pre- and post-LVAD (at 1 and 6 months) central venous pressure, pulmonary artery pressure, pulmonary capillary wedge pressure, LV ejection fraction, cardiac output, cardiac index, LV end-diastolic diameter and right ventricular (RV) end-diastolic diameter, and mitral regurgitation and tricuspid regurgitation.
Outcome variables were complications; postoperative survival at 1 month, 6 months, and 1 year; Intensive Care Unit and overall length of stay; transplantation; reoperation for aortic insufficiency; readmission rates; and cause of death.
Complications included reexploration for bleeding, driveline infections, pocket infections, pneumonia, RV failure, postoperative RV assist device (RVAD) implantation, dialysis, ventilator-dependent respiratory failure (VDRF), tracheostomy, hemorrhagic or ischemic stroke, and gastrointestinal bleeding (GIB). RV failure was defined as (1) need for inotropic support for more than 1 week or (2) need for RVAD support. VDRF was defined as inability to wean from the ventilator for at least 1 week.
Every effort is made preoperatively to optimize the patient's condition diuresis, improve peripheral perfusion, protect against RV ischemia, and correct coagulopathy.
The general criteria for LVAD implantation at our institution include the following: Patients not candidates for heart transplantation (only DT patients), with ejection fraction <25%, New York Heart Association Class 4 for 3 months or 30 days with inotrope dependence, peak exercise oxygen consumption <12 ml/kg/min, BMI between 18 and 40.
The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) scores for our patients were as follows: Class 1: 7%, Class 2: 40%, Class 3: 26%, Class 4: 20%, Class 5: 5%, and Class 6: 2%. Average waiting time for heart transplantation for our BTT patients is 125 days ± 52 when they are listed as status 1B.
Patient's demographics, operative characteristics, postoperative complications, and hemodynamic data were compared between the two groups in a univariate analysis. Continuous variables were reported as mean, standard deviation, minimum, and maximum and were compared using two-sided two-sample t-tests. Alternatively, Wilcoxon rank-sum tests were used if normality could not be assumed.
Categorical variables were reported as count and percent and were compared using Chi-square tests. Alternatively, Fisher's exact tests were used if expected cell counts were not sufficiently large. Survival at 30 days, 180 days, and 360 days was compared between ICM and IDCM using a log-rank test. Once patients were transplanted, they were censored from the survival plot.
Variables were placed in a multiple Cox proportional hazards model with 30 days, 180 days, and 360 days survival as the outcome. Variables included in the model were restricted to those that had at least 95% nonmissing values. A backward selection process was used to restrict each of the models to contain all significant predictors. Adjusted hazard ratios and 95% confidence intervals for hazard ratios were reported. Tests were considered statistically significant at P< 0.05. All analyses were performed using SAS 9.2 (Statistical Analysis System version 9 (SAS 9) - SAS Institute for advanced analytics, North Carolina State University).
| Results|| |
A total of 23 (52%) patients were presented with ICM. Average age in ICM was 63.7 ± 6.8 years as opposed to 53.9 ± 16.3 in NICM (P = 0.017). About 78% of ICM and 67% of NICM group were male (P = NS). 43.5% of ICM had undergone previous cardiac operation versus 9.5% of NICM (P = 0.012). Implant strategy was bridge to transplant in 78% of ICM and 67% of NICM (P = NS) and DT in 22% of ICM and 33% of NICM (P = NS) [Table 1].
|Table 1: Compiles the patient's demographics, comorbidities, medications, operative procedures, New York Heart Association and Interagency Registry for Mechanically Assisted Circulatory Support class|
Click here to view
Post-LVAD complications and improvements in postoperative hemodynamic measurements were also similar for both groups [Table 2] and [Table 3]. A thirty-day mortality rate was 17% in the ICM and 0% in the NICM (P = 0.06). One-year mortality was 39% for ICM and 19% for NICM (P = 0.14).
|Table 2: Details of preoperative transthoracic echo findings in patients with ischemic cardiomyopathy and nonischemic cardiomyopathy|
Click here to view
|Table 3: Details of postoperative transthoracic echo findings in patients with ischemic cardiomyopathy and nonischemic cardiomyopathy|
Click here to view
Bleeding requiring reoperation occurred in two cases (33.3%), one in each group. There were no driveline infections and no device failure.
On multivariate analysis, ICM emerged as an independent predictor of mortality (odds ratio: 3.19) [Figure 1]. Variables such as serum creatinine, inotropic or vasopressor requirement, and intraaortic balloon pump use or complex operations involving aortic or tricuspid valves at the time of LVAD placement did not impact mortality.
|Figure 1: Kaplan–Meier survival analysis of patients with ischemic cardiomyopathy versus nonischemic cardiomyopathy status postleft ventricular assist device placement|
Click here to view
| Discussion|| |
Continuous-flow LVADs have become the standard of care for patients with advanced heart failure. Comparisons of tissue samples taken at the time of implantation and at the time of transplantation showed a marked reduction in myocytolysis. Calcium uptake, calcium-binding rates, and lipid levels normalized in patients studied. Plasma norepinephrine levels decreased to near-normal levels.
Plasma brain natriuretic peptide and endotelin-1 levels correlate with both LV function and myocardial morphological improvement following LVAD implantation. However, results showed comparable reduction in the dilated cardiomyopathy and ICM groups (both P< 0.03).
Relative myocardial perfusion has been found to increase >5% from baseline in only one of six patients when Mechanical Circulatory Support (MCS) was used. These pilot study findings suggest that the decreased metabolic requirements induced by ventricular unloading correspondingly decreased blood flow requirements to physiologically inactive myocardium.
The HeartMate II device provides excellent hemodynamic support with low device-related thromboembolic events. Despite morbidity, use of the HeartMate II LVAD as bridge to transplant therapy is associated with excellent survival and low mortality rates. However, the requirements for anticoagulation therapy may be associated with increased mediastinal and GIB. The driveline infection remains a potential complication.,,,,,
Patients requiring ventricular assist device support for myocardial failure can undergo significant reverse remodeling. Explantation can lead to optimal outcome with minimal morbidity.
Some study suggested that survival at 30, 180, and 360 days after LVAD implantation is similar between the resternotomy and primary sternotomy group. No major differences in complications or hemodynamic measurements were observed.
In epidemiological surveys and in large-scale therapeutic trials, the prognosis of patients with ischemic heart failure is worse than in patients with a nonischemic etiology. Even heart transplant candidates may respond better to intensified therapy if they have nonischemic heart failure. The term “nonischemic heart failure” includes various subgroups such as hypertensive heart disease, myocarditis, alcoholic cardiomyopathy, and cardiac dysfunction due to rapid atrial fibrillation. Some of these causes are reversible. The therapeutic effect of essential drugs such as angiotensin converting enzyme inhibitors, beta blockers, and diuretics does not, in general, significantly differ between ischemic and nonischemic heart failure. However, in some trials, response to certain drugs (digoxin, tumor necrosis factor-alpha, inhibition with pentoxifylline, growth hormone, and amiodarone) was found to be better in nonischemic patients. Patients with ischemic heart failure and noncontracting ischemic viable myocardium may, on the other hand, considerably improve following revascularization. In view of prognostic and possible therapeutic differences, the etiology of heart failure should be determined routinely in all patient.
The effect of heart failure etiology on outcomes after LVAD implantation has not been fully investigated. Tsiouris et al. have shown that survival was similar for both groups with 30-day, 6-month, and 1-year survivals of 94.1%, 85.3%, and 82.4%, respectively, for ICM patients versus 95.5%, 92.4%, and 89.4%, respectively, for NIDCM patients (P = 0.743). Unlike our report, etiology of heart failure was not an independent predictor of survival in multivariate logistic regression analysis (P = 0.505). Post-LVAD complications and improvements in postoperative hemodynamic measurements were also similar for both groups. The etiology of heart failure did not appear to affect postoperative outcomes significantly.
Limitations of this study include a retrospective, single-institutional analysis and an observational, nonrandomized study subject to limitations inherent to any retrospective study. Statistical tests may have been insufficiently powered due to our relatively small sample size. Duration of follow-up was relatively short. There is a potential of inaccuracy of data retrieved retrospectively from medical records. A single-institutional study leads to selection bias.
| Conclusions|| |
This report, based on a nonmatched cohort of 44 patients, demonstrates that in an era of selective criteria for LVAD implantation, ICM emerges as an independent predictor of mortality. These patients tend to be older and are more likely to be undergoing reoperative sternotomy. These results should form the basis for a larger-scale investigation of LVAD implantation in ICM patients looking into INTERMACS/IMACS database.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Follath F. Ischemic versus non-ischemic heart failure: Should the etiology be determined? Heart Fail Monit 2001;1:122-5.
Frazier OH, Benedict CR, Radovancevic B, Bick RJ, Capek P, Springer WE, et al.
Improved left ventricular function after chronic left ventricular unloading. Ann Thorac Surg 1996;62:675-81.
Thompson LO, Skrabal CA, Loebe M, Lafuente JA, Roberts RR, Akgul A, et al.
Plasma neurohormone levels correlate with left ventricular functional and morphological improvement in LVAD patients. J Surg Res 2005;123:25-32.
Letsou GV, Sdringola S, Gregoric ID, Patel V, Myers TJ, Delgado RM, et al.
Myocardial perfusion as assessed by positron emission tomography during long-term mechanical circulatory support. Congest Heart Fail 2006;12:69-74.
Lamarche Y, Kearns M, Josan K, Bashir J, Ignaszewski A, Kaan A, et al.
Successful weaning and explantation of the HeartMate II left ventricular assist device. Can J Cardiol 2011;27:358-62.
John R, Kamdar F, Liao K, Colvin-Adams M, Boyle A, Joyce L. Improved survival and decreasing incidence of adverse events with the HeartMate II left ventricular assist device as bridge-to-transplant therapy. Ann Thorac Surg 2008;86:1227-34.
McCarthy PM, Smedira NO, Vargo RL, Goormastic M, Hobbs RE, Starling RC, et al.
One hundred patients with the HeartMate left ventricular assist device: Evolving concepts and technology. J Thorac Cardiovasc Surg 1998;115:904-12.
Ertugay S, Engin C, Nalbantgil S, Kocabas S, Balcioglu O, Engin Y, et al.
Postoperative outcomes of the largest HeartMate-II experience in Turkey. Transplant Proc 2015;47:1499-502.
Loforte A, Montalto A, Ranocchi F, Casali G, Luzi G, Monica PL, et al.
HeartMate II axial-flow left ventricular assist system: Management, clinical review and personal experience. J Cardiovasc Med (Hagerstown) 2009;10:765-71.
Granfeldt H, Peterzén B, Hübbert L, Jansson K, Ahn H. A single center experience with the HeartMate II left ventricular assist device (LVAD). Scand Cardiovasc J 2009;43:360-5.
Lim CP, Sivathasan C, Tan TE, Lim CH, Kerk KL, Sim DK. Use of left ventricular assist device (HeartMate II): A Singapore experience. Artif Organs 2014;38:543-8.
Tsiouris A, Borgi J, Karam J, Nemeh HW, Paone G, Brewer RJ, et al.
Ischemic versus nonischemic dilated cardiomyopathy: The implications of heart failure etiology on left ventricular assist device outcomes. ASAIO J 2013;59:130-5.
Tsiouris A, Brewer RJ, Borgi J, Hodari A, Nemeh HW, Cogan CM, et al.
Is resternotomy a risk for continuous-flow left ventricular assist device outcomes? J Card Surg 2013;28:82-7.
[Table 1], [Table 2], [Table 3]