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Review Article

Left Ventricular Assist Device Implantation in Hypertrophic and Restrictive Cardiomyopathy: A Systematic Review

Sreenivasan, Jayakumar*; Kaul, Risheek*; Khan, Muhammad Shahzeb; Ranka, Sagar; Demmer, Ryan T. ME§; Yuzefpolskaya, Melana; Aronow, Wilbert S.*; Warraich, Haider J.‖,#; Pan, Stephen*; Panza, Julio A.*; Cooper, Howard A.*; Naidu, Srihari S.*; Colombo, Paolo C.

Author Information
doi: 10.1097/MAT.0000000000001238



The advent of left ventricular assist devices (LVADs) has dramatically changed the medical landscape for patients with advanced heart failure (HF) refractory to medical therapy. LVAD implantation has become a standard therapeutic option to improve quality of life and survival in patients with dilated or ischemic cardiomyopathies (DCM/ICM) awaiting heart transplantation1–3 or as destination therapy.4,5 In contrast, patients with hypertrophic or restrictive cardiomyopathies (HCM/RCM) do not seem to have benefited to the same extent.6 HCM/RCM patients have small left ventricular (LV) cavities and thick, fibrotic ventricles, making LVAD implantation surgically and physiologically challenging.7,8 Importantly, patients with HCM/RCM are typically excluded from clinical trials of LVADs, and only very few HCM/RCM patients undergoing LVAD implantation have been described in small observational studies. As a result, the outcomes of this population are not well defined. Accordingly, we aimed to describe the utilization and clinical outcomes of LVAD placement in patients with HCM/RCM and compare these to patients with DCM/ICM, using a systematic review of observational studies of advanced HF management.


Data Sources and Search Strategy

We performed this systematic review in accordance with Preferred Reporting Items of Systematic Review and Meta-Analysis (PRISMA) guidelines.9 We systematically searched MEDLINE, EMBASE, and Scopus using the keywords “hypertrophic cardiomyopathy” OR “restrictive cardiomyopathy” AND “ventricular assist device” from inception through May 2019 for articles describing the use of LVAD in patients with HCM/RCM. Details of search strings used for each database are provided as a supplemental online file Study references, review articles, and book chapters were other data sources screened for additional studies. Search results were directly exported to Endnote Reference Manager version X8 (Clarivate Analytics) for removal of duplicates.

Study Selection Criteria

Original English-language articles describing the use of LVAD in patients with HCM/RCM were included in this study. After removal of duplicates, two coauthors (JS and RK) independently screened all titles, abstracts, and keywords to identify studies satisfying predetermined inclusion/exclusion criteria. Case reports, review articles, small case series with description of fewer than five patients with HCM/RCM, and abstracts without full text were excluded. References of included studies were manually reviewed to identify any additional relevant articles not captured in our search. Discrepancies regarding the inclusion or exclusion of a study were resolved after consultation with a third coauthor (MSK).

Data Extraction and Assessment of Study Quality

Baseline study characteristics, patient demographics, burden of comorbidities, pre-LVAD echocardiographic and hemodynamic parameters, perioperative and short-term in-hospital outcomes, and LVAD-related complications were extracted by two independent study investigators (JS and RK). Differences in LVAD outcomes between DCM/ICM and HCM/RCM cohorts were obtained from two of the included studies. Results were tabulated into predetermined categories and pooled for total outcomes. Study quality for biases was independently ascertained by two coauthors (JS and RK) using the New Castle Ottawa Scale for case control and cohort studies.6,8,10–13 Studies were assessed for three independent categories, including participant selection, comparability, and predefined outcomes with adequate follow-up.

Statistical Analysis

Meta-analysis was deferred because of study heterogeneity. Extracted data were pooled and tabulated for qualitative analysis. Continuous variables are expressed as mean ± standard deviation, and categorical variables are expressed as numbers with percentages. Categorical variables were compared using χ2 test, and continuous variables were compared using Student’s t-test.


Literature Search, Study Characteristics, and Quality Assessment

Using the predetermined search strategy, we identified 794 relevant studies. After removing duplicates, 368 studies were screened and assessed for eligibility criteria. After applying inclusion and exclusion criteria, six nonrandomized retrospective studies were selected for qualitative analysis. A summary of the literature search is provided in the PRISMA format (Figure, Supplemental Digital Content 1, A total of three studies described the outcomes of LVAD in HCM/RCM patients,8,10,13 two studies compared outcomes of LVAD implantation between HCM/RCM and DCM/ICM groups,8,13 and three studies described the utilization of LVADs in patients listed for transplant.6,11,12 The study by Grupper et al.10 included the patients from the study by Topilsky et al.13 in its analysis. Duplication was avoided in the descriptive analysis of baseline characteristics and outcomes. The study by Grupper et al.10 lacked a comparison group, and hence only the studies by Topilsky et al.13 and Patel et al.8 were pooled to compare LVAD-related outcomes between HCM/RCM and DCM/ICM groups. Most of the studies had a moderate to high risk of bias because of the lack of a comparison group (Table 1).

Table 1. - Study Quality Assessment Using the New Castle Ottawa Scale
Study Year Selection Comparability Outcomes
S1 S2 S3 S4 C1 C2 O1 O2 O3
Topilsky et al.13 2012 * * * * *
Grupper et al.10 2015 * * * *
Rowin et al.11 2017 * * * *
Patel et al.8 2017 * * * * * *
Sridharan et al.12 2018 * * *
Zuniga et al.6 2018 * * * *
*Each star awarded represents a low risk for bias in that particular category.
S1, representativeness of the exposed cohort; S2, selection of nonexposed cohort; S3, method of ascertainment of exposure; S4, demonstration that the outcome of interest was not present at the beginning of study; C1, comparability of cohorts based on study design; C2, any additional control factor in the study design; O1, method of outcome assessment; O2, duration of follow-up; O3, adequacy of follow-up.

Baseline Clinical Characteristics, Hemodynamics, and Echocardiographic Findings

A total of six retrospective studies were included in the systematic review.6,8,10–13 The details of each study and baseline clinical characteristics of the populations are shown in Table 2. The studies included a total of 2,766 HCM/RCM patients with advanced HF. The mean age was 51.3 ± 4.5 years, and women constituted 37.6% of the study sample. Patients within the RCM group included those with amyloid, sarcoid, or chemoradiation-related heart disease. A total of 338 patients with HCM/RCM received an LVAD, comprising 12.2% of the study population. Among these, 224 were implanted with an axial flow LVAD, whereas two of them received a centrifugal flow LVAD. The type of LVAD used was not specified for 112 patients. Among the patients listed for transplant, 4.4% (95% confidence interval [CI], 3.6%–5.2%) of the HCM/RCM patients received an LVAD compared to 18.2% (95% CI, 17.9%–18.5%) of the patients with DCM/ICM (p < 0.001).

Table 2. - Baseline Study and Patient Clinical Characteristics
Characteristic Study
Topilsky et al. Grupper et al. Rowin et al. Patel et al. Sridharan et al. Zuniga et al.
Year 2012 2015 2017 2017 2018 2018
Design Retrospective single center Retrospective single center Retrospective single center Retrospective multicenter Retrospective multicenter Retrospective multicenter
No. of patients with HCM/RCM 8 28 52 198 1,562 926
No. of patients with HCM/RCM who received LVAD 8 28 10 198 77 25
Patient characteristics
Age, mean (SD or range), y 63 (44.5–68) 57 ± 13 47 ± 13 54.9 ± 12.8 50.8 ± 13.1 47 (35.5–54.5)
No. of females (%) 2 (25) 8 (29) 22 (44) 46 (23) 570 (36.5) 396 (42.7)
African American (%) NR NR NR 38 (19.1) 258 (16.5) NR
White (%) NR NR NR 151 (76.2) 1,178 (75.4) NR
Other/unknown (%) NR NR NR 9 (4.5) 127 (8.1) NR
Diabetes mellitus NR NR NR NR 206 (13.2) 70 (7.5)
Chronic kidney disease NR NR NR NR 451 (28.9) 382 (41.2)
Creatinine, mean (mg/dl) 1.4 (0.97–2.0) 1.4 ± 0.6 NR NR NR NR
BMI (SD or range) NR 26.9 ± 3.9 NR NR NR 26.4 (22.9–30.0)
NYHA class III (%) 3 (38) NR NR 46 (23.2) NR NR
NYHA class IV (%) 5 (62) NR NR 133 (67.1) NR NR
Hemoglobin (g/dl) 12.1 ± 1 11 ± 1.8 NR NR NR NR
BMI, body mass index; HCM, hypertrophic cardiomyopathy; LVAD, left ventricular assist device; NR, not reported; NYHA, New York Heart Association; RCM, restrictive cardiomyopathy.

Hemodynamic and echocardiographic parameters of patients with HCM/RCM who received an LVAD were reported in four of the six studies8,10,12,13 (Table 3). In this group, the LV demonstrated increased wall thickness (mean septal thickness, 15 mm; 95% CI, 14.4–15.7) without significant dilation (mean left ventricular end diastolic diameter, 54.4 mm; 95% CI, 47.2–61.6). The ejection fraction (mean, 24.5%; 95% CI, 21.0–28.0) and cardiac index (mean, 1.7 L/min/m2; 95% CI, 1.6–1.7) were severely reduced. Mean pulmonary artery pressures were moderately elevated (mean, 35.3 mm Hg; 95% CI, 32.1–38.5) and right atrial pressures were severely elevated (mean, 15.0 mm Hg; 95% CI, 13.5–16.5). Severe right ventricular (RV) systolic dysfunction (22.5%; 95% CI, 9.5–35.5) and severe tricuspid regurgitation (TR) (21.8%; 95% CI, 11.6–32.0) were common.

Table 3. - Hemodynamics and Echocardiographic Characteristics of HCM/RCM Patients Who Received LVAD
Characteristics Study
Topilsky et al. (n = 8) Grupper et al. (n = 28) Patel et al. (n = 198) Rowin et al. (n = 10)
1 NR 7 (25) 28 (14.4) NR
2 NR 19 (68) 65 (33.0) NR
3 NR 2 (7) 42 (21.2) NR
4 NR NR 48 (24.2) NR
Leitz-Miller score 12 NR NR NR
Ejection fraction (%) 21 27 NR 22
LVEF <20% NR NR 99 (50) NR
LVEDD (mm) 52.5 53.7 62 47.6
LVESD (mm) 43.1 46.8 NR NR
E/e’ ratio 35 24 NR NR
Deceleration time (ms) 119 153 NR NR
RVSWI (mm Hg/ml/m2) 3.9 0.45 NR NR
Mean PA pressure (mm Hg) 33.3 33 NR 37.6
Mean RA pressure (mm Hg) 17.5 16 NR 13.9
Mean wedge pressure (mm Hg) 24.1 23 NR 26.3
Cardiac index (l/min/m2) 1.6 1.7 NR 1.7
Cardiac output (l/min) 3.2 NR NR NR
Septal thickness (mm) 16 NR NR 14
Severe RV dysfunction (%) 5 (62) 10 (35.5) 19 (9.5) NR
Pulmonary arteriolar resistance NR 5.8 NR NR
Severe MR (%) 1 (12) NR 30 (15.1) NR
Severe TR (%) 3 (37) 9 (32) 23 (11.6) NR
Destination therapy (%) 2 (25) 11 (39) 63 (32.0) 3 (30)
Bridge to transplant (%) 6 (75) 17 (61) 59 (30.0) 7 (70)
HCM/RCM, hypertrophic or restrictive cardiomyopathy; INTERMACS, Interagency Registry for Mechanically Assisted Circulatory Support; LV, left ventricle; LVAD, left ventricular assist device; LVEDD, left ventricular end diastolic diameter; LVEF, left ventricular ejection fraction; LVESD, left ventricular systolic diameter; MR, mitral regurgitation; NR, not reported; PA, pulmonary artery; RA, right atrium; RV, right ventricle; RVSWI, right ventricular stroke work index; TR, tricuspid regurgitation.

Outcomes After LVAD Implantation

Perioperative and short-term outcomes following LVAD implantation in patients with HCM/RCM are summarized in Table 4.8,10,13 Perioperative or short-term mortality was significantly higher among patients with HCM/RCM compared to that among patients with DCM/ICM (14.0% vs. 9.0%, p<0.001) (Figure 1). The incidence of postoperative RV failure requiring inotropic support was higher in the HCM/RCM group than in the DCM/ICM group (50.0% vs. 21.0%, p<0.001), and one patient with HCM/RCM required durable right ventricular assist device implantation.10,13 Postoperative complications following LVAD implantation occurred significantly more frequently among the HCM/RCM cohort compared to the DCM/ICM cohort (infection 15.5% vs. 11.2%, bleeding 40.2% vs. 12.5%, acute renal failure 15.0% vs. 5.1%, arrhythmias 18.0% vs. 7.7%, stroke 5.0% vs. 2.4%, all p<0.001) (Figure 1).

Table 4. - Outcomes of LVAD in HCM/RCM Patients
Parameters Study
Topilsky et al. (n = 8) Grupper et al. (n = 28) Patel et al. (n = 198)
Operative or short-term mortality (%) 1 (12) 4 (14) 27 (14)
Right ventricular failure (%) 4 (50) 11 (39) NR
Need for RVAD (%) 1 (12) 1 (3.5) NR
Infection (%) 7 (88) NR 25 (13)
Bleeding (%) 3 (37) 7 (25) 80 (40)
Acute renal failure (%) 3 (37) 7 (25) 28 (14)
Thromboembolic events (%) 1 (12) 2 (7) NR
Stroke (%) 1 (12) NR 9 (4.5)
Arrhythmia (%) 2 (25) 5 (18) 35 (18)
Duration of ionotropic support (h) 157 408 NR
Duration of hospital stay (d) 11 10 NR
HCM/RCM, hypertrophic or restrictive cardiomyopathy; LVAD, left ventricular assist device; NR, not reported; RVAD, right ventricular assist device.

Figure 1.
Figure 1.:
Utilization and postoperative outcomes of LVAD in HCM/RCM vs. DCM/ICM. DCM, dilated cardiomyopathy; HCM, hypertrophic cardiomyopathy; ICM, ischemic cardiomyopathy; LVAD, left ventricular assist device; RCM, restrictive cardiomyopathy.


In this systematic review of the utilization and outcomes of LVAD implantation among patients with advanced HF resulting from HCM/RCM, we report that while LVADs are used in only a minority of patients with refractory HF from HCM/RCM, perioperative and short-term mortality, RV failure, infection, bleeding, stroke, renal failure, and arrhythmias are all substantially higher in this population compared to patients with DCM/ICM. These findings have important implications for the use of LVADs in patients with HCM/RCM.

HCM/RCM patients typically have thick, fibrotic ventricles with small LV cavities, leading to surgical challenges in the placement of an LVAD as well as physiologic challenges in adapting to LVAD physiology. Outcomes were markedly worse in the HCM/RCM than in the DCM/ICM population, a finding most likely due to significant differences in the anatomy, and the underlying pathophysiology. The burned-out phase of HCM is characterized by extensive ventricular remodeling with replacement fibrosis resulting in elevated ventricular stiffness.7 This might contribute to continued diastolic dysfunction following LVAD implantation and result in recurrence of congestion. In the study by Grupper et al.,10 a smaller LV cavity size (<46 mm) did indeed correlate with an increased risk of postoperative morbidity and mortality. Novel pump designs or alternative surgical strategies such as routine myectomy at the time of LVAD placement may help to overcome some of the challenges of LVAD implantation in select patients with HCM/RCM.13

It is notable that the HCM/RCM patients who received LVADs appear to have a “burned-out” phenotype,8,10,12,13 with severely reduced LV systolic function and moderate hypertrophy.12–14 These patients seem to have progressed closer to a DCM phenotype with relatively dilated LV, reduced EF, and thinner septum compared to typical HCM/RCM patients. Despite the change in phenotype, outcomes were significantly worse in patients with HCM/RCM. It is possible that these patients were implanted later during their disease course given the hesitancy posed by anatomic and physiologic challenges. This may lead to worsening hemodynamics, poor RV function and also a decline in functional and nutritional status. Furthermore, in patients with restrictive cardiomyopathy, multiorgan dysfunction by the underlying systemic disease process might have led to worse outcomes, a possibility supported by our study findings that the incidence of noncardiac complications like infections, bleeding, and acute renal failure were higher among the HCM/RCM cohort. Future studies investigating outcomes of patients with RCM separately from that of HCM cohort compared to DCM/ICM will be needed to further delineate the underlying cause of worse outcomes following LVAD among these patients.

The present analysis also reveals a high risk of RV failure following LVAD implantation in HCM/RCM patients. Postoperative RV failure seems to be in part a consequence of significant preexisting RV systolic dysfunction. In our review, at least one-fourth of the patients with HCM/RCM had severe RV systolic dysfunction and severe TR before LVAD implantation. LVAD mechanics cause shifting of the interventricular septum towards the LV cavity, potentially worsening the severity of TR and resulting in further compromise of RV systolic function. In addition, enhancing cardiac output with the LVAD increases the hemodynamic demands on the RV. This may lead to unmasking or worsening of preexisting RV function. These mechanisms may explain the common need for prolonged inotropic support of the RV—and occasionally right ventricular assist device implantation—following LVAD in patients with HCM/RCM.

In current clinical practice, LVAD use in HCM/RCM patients appears to be limited to highly selected cases with advanced HF who might have exhausted all possible alternative therapeutic options, constituting a comparatively sicker cohort compared to that of DCM/ICM patients. This may explain the increased risk of perioperative complications such as renal failure (including the need for dialysis), serious infections, higher bleeding risk, arrhythmias, and stroke. Specifically, the increased incidence of postoperative arrhythmias may be related to extensive cardiac fibrosis (or granulomas in the case of sarcoidosis) in patients with HCM/RCM.

Both the 2011 American College of Cardiology/American Heart Association (ACC/AHA) guidelines on the diagnosis and management of HCM and the 2016 International Society for Heart and Lung Transplantation guidelines recommend transplantation, but not LVAD implantation, as an option available to patients with HCM/RCM who develop medically refractory HF.15–17 Although outcomes after heart transplantation in patients with HCM/RCM are similar, and perhaps even favorable, compared to patients with other cardiovascular diseases,14,18 waitlist mortality of up to 42.3% remains a challenging issue.6,13 Under the current United Network of Organ Sharing heart allocation system in the United States, patients on mechanical circulatory support are generally deemed higher priority than those not requiring, or ineligible, for mechanical circulatory support. Consequently, given the aforementioned challenges with, and limited utilization of LVADs in patients with HCM/RCM, this subgroup may not be well accommodated by the current allocation system.11

This systematic review has several limitations. First, the original reports included were retrospective and observational in design, which may have resulted in a selection bias. Second, since there may be preconceived notions about the futility of LVAD implantation in HCM/RCM patients, it is likely that patients represented in these studies were at the very end of the HF syndrome spectrum, which in turn could lead to worse outcomes. Third, although HCM and RCM were grouped together in the original investigations given their small LV cavity size and LVAD physiology, morbidity and mortality outcomes between the two groups can be quite different, which we were unable to separate. Fourth, the majority of the studies that provided data on the type of LVAD employed used axial flow LVADs (HeartMate II). The differences in unloading conditions between axial versus centrifugal flow LVADs and also LVAD design can greatly influence outcomes. Fifth, study quality assessment suggests a moderate to high risk of bias, mostly due to lack of control groups. Sixth, our review was generally limited to short-term clinical outcomes following LVAD implantation, as long-term comparative outcomes were only reported in a single study. Finally, heterogeneity of studies and the fact that not all baseline variables and outcomes of interest were consistently reported among all studies preclude a quantitative meta-analysis on this topic. Notwithstanding these limitations, this review serves as the best available systematic scientific summary of the literature on this topic.


In this systematic review, we found that LVADs are used infrequently for refractory HF in patients with HCM/RCM. Compared with DCM/ICM, LVAD implantation in HCM/RCM is associated with a higher risk of perioperative and short-term mortality, RV failure, infection, bleeding, stroke, renal failure, and arrhythmias. Prospective studies with novel LVAD designs and alternative surgical strategies, tailored for patients with HCM/RCM, are warranted with the goal of improving outcomes for these challenging patients.


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hypertrophic cardiomyopathy; restrictive cardiomyopathy; dilated cardiomyopathy; mechanical circulatory support; left ventricular assist devices; refractory heart failure

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