Advertisement
Heart, Lung and Circulation

Impact of Ischaemic and Dilated Cardiomyopathy on Short-Term and Long-Term Survival After Ventricular Assist Device Implantation: A Single-Centre Experience

Published:September 28, 2021DOI:https://doi.org/10.1016/j.hlc.2021.08.017

      Background

      Prognosis of patients with end-stage heart failure is known to be impacted by the aetiology of heart failure (HF). Ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the most frequent pathologies necessitating ventricular assist device (VAD) support in these patients. However, the specific impact of ICM and DCM in clinical outcomes after VAD implantation remains unclear. Therefore, this study aimed to analyse clinical differences in ICM and DCM patients after LVAD surgery from the current institution.

      Methods

      All consecutive patients from the LVAD centre were included in this retrospective study. To analyse specific differences in in-hospital outcomes, patients were divided into two groups: ICM and DCM. Long-term follow-up was calculated by Kaplan-Meier estimation of survival.

      Results

      Between January 2010 and July 2020, 60 consecutive patients underwent LVAD implantation at the institution: 36 patients (60%) were supported due to end-stage ICM and 24 patients (40%) in regard of therapy-refractory DCM. Baseline characteristics showed no between-group differences. The ICM patients showed a clear trend to higher amount of additional cardiac procedures during VAD surgery (36% ICM vs 12% DCM; p=0.052). In-hospital mortality was comparable between ICM and DCM patients (36% ICM vs 21% DCM; p=0.206). A trend towards higher frequency of pump thrombosis was seen in DCM patients (p=0.080). Long-term survival was comparable between the groups.

      Conclusion

      The aetiology of heart failure did not impact short-term or long-term clinical outcomes after VAD surgery. Multicentre registry data are necessary to substantiate these findings.

      Keywords

      Introduction

      A decrease in organ donors has led in an increase in waiting times for heart transplantation, and left ventricular assist device (LVAD) therapy has switched from bridge to transplant to bridge to destination in the majority of implantations performed over the last few years [
      • Gustafsson F.
      • Rogers J.G.
      Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes.
      ]. Meanwhile, LVAD surgery is an established treatment option for patients with advanced cardiomyopathy [
      • Lietz K.
      • Long J.W.
      • Kfoury A.G.
      • Slaughter M.S.
      • Silver M.A.
      • Milano C.A.
      • et al.
      Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection.
      ,
      • Null N.
      • Hunt S.A.
      • Abraham W.T.
      • Chin M.H.
      • Feldman A.M.
      • Francis G.S.
      • et al.
      2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults.
      ,
      • Radovancevic B.
      • Vrtovec B.
      • Frazier O.H.
      Left ventricular assist devices: an alternative to medical therapy for end-stage heart failure.
      ]. Depending on the form of heart failure (HF), prognosis is influenced by aetiology, age, comorbidities, and individual progression of HF [
      • Kheirbek R.E.
      • Alemi F.
      • Fletcher R.
      Heart failure prognosis: comorbidities matter.
      ]. Among the variety of HF forms, ischaemic cardiomyopathy (ICM) and dilated cardiomyopathy (DCM) are the main causes of chronic HF [
      • Cowie M.R.
      • Wood D.A.
      • Coats A.J.
      • Thompson S.G.
      • Poole-Wilson P.A.
      • Suresh V.
      • et al.
      Incidence and aetiology of heart failure; a population-based study.
      ]. Congruent with epidemiological data, ICM and DCM patients present the largest group of patients treated with LVAD [
      • Tyminska A.
      • Kaplon-Cieslicka A.
      • Balsam P.
      • Ozieranski K.
      • Wancerz A.
      • Peller M.
      • et al.
      Ischemic versus dilated cardiomyopathy - differences in clinical characteristics and prognosis depending on heart failure etiology.
      ]. In 2002, Heerdt et al. demonstrated LVAD-induced reverse ventricular remodelling in ICM patients, but not in DCM patients [
      • Heerdt P.M.
      • Schlame M.
      • Jehle R.
      • Barbone A.
      • Burkhoff D.
      • Blanck T.J.
      Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device.
      ]. Symons et al. showed in their multicentre trial that coronary artery endothelial function was significantly more improved in LVAD-supported ICM patients compared with DCM patients [
      • Symons J.D.
      • Deeter L.
      • Deeter N.
      • Bonn T.
      • Cho J.M.
      • Ferrin P.
      • et al.
      Effect of continuous-flow left ventricular assist device support on coronary artery endothelial function in ischemic and nonischemic cardiomyopathy.
      ]. Translation of these findings into clinical outcomes is necessary to identify the impact of the underlying HF after LVAD implantation. In this context, data comparing clinical outcomes of ICM and DCM patients after LVAD surgery are scarce and lacking in current literature.
      Therefore, this study aimed to analyse clinical differences in ICM and DCM patients after LVAD surgery, from the current institution, with respect to in-hospital and long-term outcomes.

      Methods

      The Institutional Review Board approved this study. Informed written consent was waived due to the retrospective design. It included 60 consecutive patients who received continuous-flow, centrifugal pump LVAD for either destination or bridge to transplant therapy between February 2010 and December 2020. All patients met the medical policy guideline of New York Heart Association (NYHA) class IV HF. Patients were divided into two groups depending on type of HF: ICM, n=36 and DCM, n=24.

      Endpoints and Definitions

      The primary endpoint was in-hospital mortality. Long-term survival was assessed by Kaplan-Meier-survival curve. In-hospital mortality was defined as death from any cause within the in-patient stay. Acute kidney injury was defined by increases in serum creatinine and/or the need for dialysis. The current Kidney Disease: Improving Global Outcomes (KDIGO) guidelines modified the RIFLE criteria
      Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease.
      to include changes in creatinine as small as 0.3 mg/dL. In general, INTERMACS
      Interagency Registry for Mechanically Assisted Circulatory support.
      profiles I–III present inotrope-dependent patients from ‘crash and burn’ (INTERMACS class I) to those who are haemodynamically stable on inotrope medication (INTERMACS class III), and profiles IV–VII demonstrate non-inotrope-dependent patients with diverse forms of severe HF symptoms. According to the INTERMACS registry, right ventricular failure is defined as symptoms and signs of sustained right ventricular (RV) dysfunction (defined as central venous pressure >18 mmHg with a cardiac index <2.0 L/min/m2 in the absence of pulmonary capillary wedge pressure >18 mmHg, malignant arrhythmias or pneumothorax), necessitating right ventricular assist device (RVAD) or inotropic therapy for >7 days any time after LVAD implantation.

      Follow-Up

      Patients were followed up systematically at the University Hospital of Cologne during their regular outpatient care. Mean follow-up among survivors was 50.4 months (range, 36–64.8 months).

      Statistical Analysis

      Statistical analysis was performed using Statistical Package for Social Sciences, version 23.0 (SPSS IBM., Armonk, NY, USA). Baseline, intraprocedural, and follow-up data up to 30 days were retrospectively collected and entered into a standardised database and analysed. Data are presented as absolute numbers and percentages for categorical variables. Continuous data were evaluated for normality using one sample Kolmogorov-Smirnov test and were expressed as the mean±standard deviation (SD) in cases of normally distributed or median (interquartile range) in cases of non-normally distributed continuous variables. Univariate analysis was performed using either Student t-test or Mann-Whitney U test for normally and non-normally distributed continuous variables, respectively. Pearson’s χ2 or Fisher exact tests were used for comparison of categorical data, depending on the minimum expected count in each cross-tab. Long-term data were estimated by Kaplan-Meier-survival curve and Log-rank-test. A level of significance was set at two-tailed p<0.05.

      Results

      Between January 2010 and July 2020, 60 consecutive patients underwent LVAD implantation at the current institution. Thirty-six (36) patients (60%) were supported due to end-stage ICM and 24 patients (40%) due to therapy-refractory DCM. Baseline characteristics are presented in Table 1. Age did not differ between the groups (58±11 ICM vs 58±10 DCM; p=0.976). Furthermore, ICM (92%) and DCM (87%) were more frequent in men than in women. The aim of surgery showed no difference regarding HF. Comorbidities were generally comparable between the groups. Previous myocardial infarction (p=0.079) and pulmonary hypertension (p=0.076) showed a trend towards a higher incidence in ICM patients and chronic kidney disease (p=0.085) in DCM patients. Previous cardiac surgery procedures showed no between-group difference.
      Table 1Baseline characteristics of patients supported with LVAD.
      ICM (n=36)DCM (n=24)P-value
      Age (yr)58±1158±100.976
      Male33 (92)21 (87)0.598
      Height (m)176 (170;180)176 (175;180)0.989
      Weight (kg)79 (73;89)81 (75;90)0.917
      BMI (kg/m2)26 (24;29)26 (23;31)0.200
      Aim of surgery
       Bridge to transplant8 (22)7 (29)0.543
       Destination therapy18 (50)13 (54)0.752
       Ultima ratio10 (28)4 (17)0.319
      Comorbidities
       NYHA IV34 (100)26 (100)0.688
       COPD8 (22)8 (33)0.290
       Pulmonary hypertension16 (44)5 (21)0.076
       Peripheral vascular disease13 (36)6 (25)0.203
       Coronary artery disease23 (67)13 (54)0.571
       Chronic kidney disease18 (50)18 (75)0.085
       Atrial fibrillation16 (44)10 (42)0.942
       Diabetes mellitus II10 (28)9 (37)0.507
       Cerebral vascular disease11 (31)6 (25)0.427
       Prior myocardial infarction24 (67)10 (42)0.079
      Previous cardiac surgery
       Re-do surgery9 (25)6 (25)0.611
       Single CABG6 (17)6 (25)0.309
       Tricuspid valve repair/replacement1 (3)0 (0)0.174
       Aortic valve replacement4 (11)3 (12)0.775
       Mitral valve replacement2 (6)1 (4)0.208
      Abbreviations: ICM, ischaemic cardiomyopathy; DCM, dilated cardiomyopathy; BMI, body mass index; NYHA, New York Heart Association class; COPD, chronic obstructive pulmonary disease; LVAD, left ventricular assist device; CABG, coronary artery bypass graft.
      Laboratory parameters (creatinine, albumin, bilirubin) prior to LVAD surgery did not differ (Table 2). Echocardiographic data were comparable, resulting in 19±7% left ventricular ejection fraction in ICM patients, and 17±7% in DCM patients. DCM patients showed a trend towards a higher cardiac index (p=0.062). INTERMACS profile distribution was comparable between the groups. Most patients were in INTERMACS profile 1–3 (47% ICM vs 42% DCM; p=0.778).
      Table 2Laboratory parameter, echocardiographic data, and INTERMACS profile prior to surgery.
      ICM (n=36)DCM (n=24)P-value
      Laboratory parameter
       Serum creatinine (mg/dL)1.6 (1.1;2,1)1.5 (1.2;2)0.784
       Albumin (g/L)30±1032±140.693
       Total bilirubin (mg/dL)1.2 (0.5;2.1)1.3 (0.7;3.9)0.956
      Echocardiographic data
       LVEDD (mm)67±1071±90.342
       TAPSE (mm)14±413±40.811
       sPAP (mmHg)53±855±120.435
       Cardiac index (L/min/m2)1.25 (1.2;1.3)1.4 (1.2;1.7)0.062
       LVEF (%)19±717±70.435
      INTERMACS profile
       Profile 1–317 (47)10 (42)0.778
       Profile 47 (19)4 (17)0.843
       Profile 56 (17)6 (25)0.381
       Profile 66 (17)4 (17)0.942
       Profile 70 (0)0 (0)-
      Abbreviations: LVEDD, left ventricular end diastolic diameter; TAPSE, tricuspid annular plane systolic excursion; sPAP, systolic pulmonary artery pressure; LVEF, left ventricular ejection fraction; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory support.
      Intraoperative data are summarised in Table 3. The majority of patients were supported with Heart Ware HVAD (Heart Ware International Inc., Framingham, MA, USA) (81% ICM vs 75% DCM; p=0.542). DCM patients significantly more often received HeartMate III (Abbott, Chicago, IL, USA) (p<0.001). ICM patients showed a clear trend to higher amounts of additional cardiac procedures during LVAD surgery (36% ICM vs 12% DCM; p=0.052). Incidences of temporary RVAD due to right ventricular failure and concomitant ECMO support were comparable.
      Table 3Intraoperative data.
      ICM (n=36)DCM (n=24)P-value
      Heart Ware HVAD29 (81)18 (75)0.542
      Heart Mate III1 (3)6 (25)<0.001
      BiVAD (Berlin Heart)1 (3)0 (0)0.174
      CPB time (min)86 (64;126)89 (71;121)0.787
      Cross-clamp time (min)0 (0)0 (0)-
      Procedure time (min)182 (143;227)187 (148;211)0.787
      Combined surgery13 (36)3 (12)0.052
      Chest packing6 (17)6 (25)0.391
      IABP6 (17)2 (8)0.417
      Temporary RVAD4 (11)1 (4)0.340
      ECMO11 (31)4 (17)0.296
      Abbreviations: BiVAD, bi-ventricular assist device; CPB, cardiopulmonary bypass; IABP, intra-aortic balloon pump; RVAD, right ventricular assist device; ECMO, extracorporeal membrane oxygenation.
      Postoperative inotropic therapy with milrinone significantly differed between the groups (0.2 (0.05;0.2) μg/kg/min ICM vs. 0.25 (0.2;0.3) μg/kg/min DCM; p<0.001). Laboratory parameters showed no difference postoperatively (Table 4).
      Table 4Postoperative catecholamine therapy and laboratory parameters.
      ICM (n=36)DCM (n=24)P-value
      Inotropic and vasoactive supports
       Adrenalin (μg/kg/min)0.1 (0.1;0.2)0.2 (0.1;0.2)0.280
       Milrinone (μg/kg/min)0.2 (0.05;0.2)0.25 (0.2;0.3)<0.001
       Noradrenalin (μg/kg/min)0.25 (0.18;0.37)0.25 (0.19;0.4)0.979
      Laboratory parameter
       Creatinine (mg/dL)2.1 (1.5;2.5)1.6 (1.2;2.2)0.053
       ASAT (U/L)126 (59;582)91 (44;158)0.406
       ALAT (U/L)67 (29;372)39 (24;119)0.782
       Albumin (g/L)23 (16;29)24 (20;29)0.904
       Platelets (g/L)123±67126±740.894
       Haematocrit (%)28 (26;32)28 (26;31)0.861
      Transfusions
       RBC (units)13 (6;26)10 (2;33)0.791
       Platelets (units)2 (0;4)1 (0;4)0.346
       FFP (units)4 (1;9)4 (0.25;12)0.878
      Abbreviations: ASAT, aspartate aminotransferase; ALAT, alanine aminotransferase; RBC, red blood cells; FFP, fresh frozen plasma.
      Outcomes are presented in Table 5. In-hospital mortality was comparable between ICM and DCM patients (36% ICM vs 21% DCM; p=0.206). Median hospital stay was 28 (6;53) days in ICM patients and 38 (24;83) days in DCM patients (p=0.349). Moreover, there was a trend towards more frequent pump thrombosis in DCM patients (p=0.080). Other adverse in-patient outcomes did not differ between the groups. No other differences were noted between ICM and DCM patients in terms of adverse events.
      Table 5In-hospital outcomes after LVAD surgery.
      ICM (n=36)DCM (n=24)P-value
      In-hospital mortality13 (36)5 (21)0.206
      ICU stay (d)12 (5;30)20 (9;57)0.349
      Hospital stay (d)28 (6;53)38 (24;83)0.349
      Adverse outcomes
       Bleeding volume in 24 hr (mL)1,300 (1,020;2,140)1,200 (1,100;1,250)0.350
       Re-thoracotomy7 (19)5 (21)0.807
       Pump thrombosis2 (6)2 (8)0.080
       RVAD thrombosis1 (3)0 (0)0.410
       Right heart failure12 (33)5 (21)0.448
       RI requiring dialysis17 (42)8 (33)0.503
       Stroke3 (8)3 (12)0.174
       Hepatic dysfunction6 (17)4 (17)0.820
       Cardiac arrhythmias13 (36)9 (37)0.614
       Worsening HF7 (19)1 (4)0.124
       Haemolysis7 (19)3 (12)0.621
       Driveline infection6 (17)3 (12)0.812
       Sepsis8 (22)6 (25)0.591
      Abbreviations: ICU, intensive care unit; RVAD, right ventricular assist device; RI, renal insufficiency; HF, heart failure; ICM, ischaemic cardiomyopathy; DCM, dilated cardiomyopathy.

      Overall Long-Term Survival and Survival for ICM and DCM Patients After LVAD Implantation

      Kaplan-Meier analysis (Figure 1) from day 90 showed no difference in survival between patients with ICM compared with those with DCM (log-rank test, p=0.197). Kaplan-Meier estimation for long term-survival showed no significant difference between patients suffering from ischaemic and dilated cardiomyopathy (Figure 2) (log-rank test; p=0.105).
      Figure thumbnail gr1
      Figure 1Kaplan-Meier analysis from day 90 showed no difference in survival between patients with ischaemic cardiomyopathy (ICM) compared with those with dilated cardiomyopathy (DCM) (log-rank test, p=0.197).
      Abbreviation: LVAD, left ventricular assist device.
      Figure thumbnail gr2
      Figure 2Kaplan-Meier estimation for long term-survival showed no significant difference between patients suffering from ischaemic cardiomyopathy and dilated cardiomyopathy (log-rank test; p=0.105).
      Abbreviations: DCM, dilated cardiomyopathy; ICM, ischaemic cardiomyopathy; LVAD, left ventricular assist device.

      Discussion

      This study was performed to investigate whether aetiology of HF impacts either short-term or long-term outcomes in LVAD patients. From observation, no significant differences were obvious, indicating comparable results for both group of patients in mid-volume centres. Additionally, long-term survival up to 5 years was comparable.
      Diverse studies have shown that patients with ischaemic cardiomyopathy have reduced survival compared with patients with dilated cardiomyopathy [
      • Tyminska A.
      • Kaplon-Cieslicka A.
      • Balsam P.
      • Ozieranski K.
      • Wancerz A.
      • Peller M.
      • et al.
      Ischemic versus dilated cardiomyopathy - differences in clinical characteristics and prognosis depending on heart failure etiology.
      ]. Both cardiomyopathies are characterised by some degree of fibrosis, remodelling, and a variable amount of viable myocardium, with a higher risk of sudden cardiac death in ICM patients [
      • Tompkins B.A.
      • Rieger A.C.
      • Florea V.
      • Banerjee M.N.
      • Natsumeda M.
      • Nigh E.D.
      • et al.
      Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy.
      ]. The observed survival in the current cohort was similar, despite a trend towards a higher amount of pulmonary hypertension and prior myocardial infarction in ICM patients.
      In contrast to the current findings, some studies have shown that ICM patients have diminished survival compared with DCM patients. Likoff et al. reported significantly higher mortality at 12 months for patients with ICM compared with DCM (36% vs 24%, respectively; p<0.001) [
      • Likoff M.J.
      • Chandler S.L.
      • Kay H.R.
      Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.
      ]. Another study showed that an ischaemic aetiology for HF was an independent predictor of mortality [
      • Stevenson L.W.
      • Tillisch J.H.
      • Hamilton M.
      • Luu M.
      • Chelimsky-Fallick C.
      • Moriguchi J.
      • et al.
      Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy.
      ]. However, Chou et al. reported, concomitant with the current analysis, similar survival between both groups, with a 1-year survival of 72% for ICM patients versus 74% for DCM patients [
      • Chou B.
      • Lamba H.K.
      • Long G.
      • Parikh V.
      • Chatterjee S.
      • George J.
      • et al.
      Outcomes of LVAD implantation in ischemic versus nonischemic cardiomyopathy.
      ]. Moreover, the aetiology of HF in the Studies of Left Ventricular Dysfunction (SOLVD) registry also did not affect mortality [
      • Sisti N.
      • Mandoli G.E.
      • Sciaccaluga C.
      • Valente S.
      • Mondillo S.
      • Cameli M.
      Insight into atrial fibrillation in LVAD patients: from clinical implications to prognosis.
      ]; this is a registry of 6,336 patients with congestive HF or LV dysfunction that is designed to describe the clinical course of an unselected group of patients.
      In addition, Tsiouris et al. presented data from their LVAD program, comparing results of patients regarding the aetiology of HF [
      • Tsiouris A.
      • Borgi J.
      • Karam J.
      • Nemeh H.W.
      • Paone G.
      • Brewer R.J.
      • et al.
      Ischemic versus nonischemic dilated cardiomyopathy: the implications of heart failure etiology on left ventricular assist device outcomes.
      ]. Survival was similar in both groups within 30 days, 6 months, and 1 year after LVAD surgery (p=0.743) [
      • Tsiouris A.
      • Borgi J.
      • Karam J.
      • Nemeh H.W.
      • Paone G.
      • Brewer R.J.
      • et al.
      Ischemic versus nonischemic dilated cardiomyopathy: the implications of heart failure etiology on left ventricular assist device outcomes.
      ]. Moreover, the type of cardiomyopathy was not an independent predictor of survival in multivariate logistic regression analysis. Therefore, the authors corroborated the current findings and stated that aetiology of cardiomyopathy does not influence outcomes after LVAD surgery. It is believed that the current study is the first to describe these results and also for a follow-up period of 5 years. Additionally, clinical parameters and short-term outcomes in this analysis were comparable and did not indicate a difference between the analysed cohorts. In this context, several questions arise about why outcomes appear similar, despite known differences in structural myocardial remodelling following LVAD surgery regarding underlying cardiomyopathy [
      • Bruggink A.H.
      • van Oosterhout M.F.
      • de Jonge N.
      • Ivangh B.
      • van Kuik J.
      • Voorbij R.H.
      • et al.
      Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern.
      ]. There is evidence for specific downregulation and upregulation of extracellular matrix-associated proteins during VAD circulation, depending on the aetiology of HF [
      • de Weger R.A.
      • Schipper M.E.
      • Siera-de Koning E.
      • van der Weide P.
      • van Oosterhout M.F.
      • Quadir R.
      • et al.
      Proteomic profiling of the human failing heart after left ventricular assist device support.
      ]. However, available data suggest that sequential beneficial effects diminish regarding in-hospital outcomes.

      Limitations

      This study had several limitations. First, it was an observational, non-randomised study and subject to limitations inherent to any retrospective study. Second, statistical tests may have been insufficiently powered due to the relatively small sample size. Third, the potential inaccuracy of data retrieved from medical records reduced the power of the study. Finally, it was a single institutional study and selection bias may have been introduced.

      Conclusion

      Aetiology of heart failure did not impact short-term or long-term clinical outcomes in mid-volume assist device centres after VAD surgery. To translate known pathophysiologic differences into clinical outcomes, experimental data might be necessary. Moreover, multicentre registry data could substantiate these findings, which are congruent with the majority of current studies.

      Disclosures

      The authors have nothing to disclose.

      Conflicts of Interest

      The authors declare no conflicts of interest.

      Funding Sources

      This research did not receive any specific grant from funding.

      Acknowledgements

      None.

      References

        • Gustafsson F.
        • Rogers J.G.
        Left ventricular assist device therapy in advanced heart failure: patient selection and outcomes.
        Eur J Heart Failure. 2017; 19: 595-602
        • Lietz K.
        • Long J.W.
        • Kfoury A.G.
        • Slaughter M.S.
        • Silver M.A.
        • Milano C.A.
        • et al.
        Outcomes of left ventricular assist device implantation as destination therapy in the post-REMATCH era: implications for patient selection.
        Circulation. 2007; 116: 497-505
        • Null N.
        • Hunt S.A.
        • Abraham W.T.
        • Chin M.H.
        • Feldman A.M.
        • Francis G.S.
        • et al.
        2009 Focused update incorporated into the ACC/AHA 2005 Guidelines for the Diagnosis and Management of Heart Failure in Adults.
        Circulation. 2009; 119: e391-e479
        • Radovancevic B.
        • Vrtovec B.
        • Frazier O.H.
        Left ventricular assist devices: an alternative to medical therapy for end-stage heart failure.
        Curr Opin Cardiol. 2003; 18: 210-214
        • Kheirbek R.E.
        • Alemi F.
        • Fletcher R.
        Heart failure prognosis: comorbidities matter.
        J Palliat Med. 2015; 18: 447-452
        • Cowie M.R.
        • Wood D.A.
        • Coats A.J.
        • Thompson S.G.
        • Poole-Wilson P.A.
        • Suresh V.
        • et al.
        Incidence and aetiology of heart failure; a population-based study.
        Eur Heart J. 1999; 20: 421-428
        • Tyminska A.
        • Kaplon-Cieslicka A.
        • Balsam P.
        • Ozieranski K.
        • Wancerz A.
        • Peller M.
        • et al.
        Ischemic versus dilated cardiomyopathy - differences in clinical characteristics and prognosis depending on heart failure etiology.
        Eur Heart J. 2017; 38
        • Heerdt P.M.
        • Schlame M.
        • Jehle R.
        • Barbone A.
        • Burkhoff D.
        • Blanck T.J.
        Disease-specific remodeling of cardiac mitochondria after a left ventricular assist device.
        Ann Thorac Surg. 2002; 73: 1216-1221
        • Symons J.D.
        • Deeter L.
        • Deeter N.
        • Bonn T.
        • Cho J.M.
        • Ferrin P.
        • et al.
        Effect of continuous-flow left ventricular assist device support on coronary artery endothelial function in ischemic and nonischemic cardiomyopathy.
        Circ Heart Fail. 2019; 12: e006085
        • Tompkins B.A.
        • Rieger A.C.
        • Florea V.
        • Banerjee M.N.
        • Natsumeda M.
        • Nigh E.D.
        • et al.
        Comparison of mesenchymal stem cell efficacy in ischemic versus nonischemic dilated cardiomyopathy.
        J Am Heart Assoc. 2018; 7
        • Likoff M.J.
        • Chandler S.L.
        • Kay H.R.
        Clinical determinants of mortality in chronic congestive heart failure secondary to idiopathic dilated or to ischemic cardiomyopathy.
        Am J Cardiol. 1987; 59: 634-638
        • Stevenson L.W.
        • Tillisch J.H.
        • Hamilton M.
        • Luu M.
        • Chelimsky-Fallick C.
        • Moriguchi J.
        • et al.
        Importance of hemodynamic response to therapy in predicting survival with ejection fraction less than or equal to 20% secondary to ischemic or nonischemic dilated cardiomyopathy.
        Am J Cardiol. 1990; 66: 1348-1354
        • Chou B.
        • Lamba H.K.
        • Long G.
        • Parikh V.
        • Chatterjee S.
        • George J.
        • et al.
        Outcomes of LVAD implantation in ischemic versus nonischemic cardiomyopathy.
        J Heart Lung Transplant. 2019; 38: S449
        • Sisti N.
        • Mandoli G.E.
        • Sciaccaluga C.
        • Valente S.
        • Mondillo S.
        • Cameli M.
        Insight into atrial fibrillation in LVAD patients: from clinical implications to prognosis.
        Pulse. 2020; 8: 2-14
        • Tsiouris A.
        • Borgi J.
        • Karam J.
        • Nemeh H.W.
        • Paone G.
        • Brewer R.J.
        • et al.
        Ischemic versus nonischemic dilated cardiomyopathy: the implications of heart failure etiology on left ventricular assist device outcomes.
        Asaio J. 2013; 59: 130-135
        • Bruggink A.H.
        • van Oosterhout M.F.
        • de Jonge N.
        • Ivangh B.
        • van Kuik J.
        • Voorbij R.H.
        • et al.
        Reverse remodeling of the myocardial extracellular matrix after prolonged left ventricular assist device support follows a biphasic pattern.
        J Heart Lung Transplant. 2006; 25: 1091-1098
        • de Weger R.A.
        • Schipper M.E.
        • Siera-de Koning E.
        • van der Weide P.
        • van Oosterhout M.F.
        • Quadir R.
        • et al.
        Proteomic profiling of the human failing heart after left ventricular assist device support.
        J Heart Lung Transplant. 2011; 30: 497-506