Contemporary Outcomes of Pediatric Restrictive Cardiomyopathy: A Single-Center Experience.

BACKGROUND: Pediatric restrictive cardiomyopathy (RCM) has high mortality in historical cohorts, and traditional management often involves early referral for heart transplantation (HTx). This study sought to determine outcomes of pediatric RCM at a center that has favored medical management over early listing for HTx. METHODS: All patients (N = 43) with pure RCM phenotype (RCM, N = 26) and hypertrophic cardiomyopathy with restrictive physiology (RCM/HCM, N = 17) managed at our center over a 15-year period were investigated. Outcomes of those listed for HTx (N = 18) were compared to a benchmark of contemporaneous pediatric RCM patients in the UNOS database (N = 377). Proportional hazards models were used to determine predictors of adverse outcomes. RESULTS: The mean age was 11 ± 9 years and 49% were male. 14 of 18 patients listed received HTx. Overall mortality (12%) was identical between the phenotypes; however, RCM patients were more likely to be listed (P = 0.001) and receive HTx (P = 0.02) compared to RCM/HCM. Prior to HTx, 60% had documented arrhythmia, 16% had cardiac arrest, and 7% required mechanical circulatory support. 4 of 17 patients with an ICD/PM received device therapies (four of five shocks appropriate for VT/VF, and two effective anti-tachycardia pacing interventions). Outcomes of those listed for HTx at our center were similar to the UNOS benchmark. In multivariate analysis, markers of congestive heart failure were associated with adverse outcomes. CONCLUSION: Heart failure and arrhythmia treatments can delay or possibly prevent the need for HTx in some cases of pediatric RCM. Survival post-HTx is not compromised using this approach.

Spirometric impairments, cardiovascular outcomes, and noncardiovascular death in older persons.

BACKGROUND: In prior work involving older persons, the reported associations of spirometric impairments with cardiovascular outcomes may have been confounded by age-related changes in lung function. Hence, using more age-appropriate spirometric criteria from the Global Lung Function Initiative (GLI), we have evaluated the associations of spirometric impairments, specifically restrictive-pattern and airflow-obstruction, with cardiovascular death (CV-death) and hospitalization (CV-hospitalization). In these analyses, we also evaluated the competing outcome of noncardiovascular death (nonCV-death) and calculated measures of relative and absolute risk. METHODS: Our study sample was drawn from the Cardiovascular Health Study (CHS), including 4232 community-dwelling white persons aged ≥65 years. Multivariable regression models included the following baseline predictors: GLI-defined restrictive-pattern and airflow-obstruction, age, male gender, obesity, waist circumference, current smoker status, ≥10 pack-years of smoking, hypertension, dyslipidemia, diabetes, and cardiovascular and cerebrovascular disease. Outcomes included adjudicated CV-death, CV-hospitalization, and nonCV-death, ascertained over 10 years of follow-up. Measures of association included hazard ratios (HRs), rate ratios (RRs), and average attributable fraction (AAF), each with 95% confidence intervals. RESULTS: Restrictive-pattern and airflow-obstruction were associated with CV-death (adjusted HRs: 1.57 [1.18, 2.09] and 1.29 [1.04, 1.60]) and with nonCV-death (adjusted HRs: 2.10 [1.63, 2.69] and 1.79 [1.51, 2.12]), respectively. Airflow-obstruction, but not restrictive-pattern, was also associated with CV-hospitalization (adjusted RRs: 1.18 [1.02, 1.36] and 1.20 [0.96, 1.50], respectively). The adjusted AAFs of restrictive-pattern and airflow-obstruction were 1.68% (0.46, 3.06) and 2.35% (0.22, 4.72) for CV-death, and 3.44% (1.97, 5.08) and 7.77% (5.15, 10.60) for nonCV-death, respectively. CONCLUSION: Assessment of GLI-defined spirometric impairments contributes to broad geriatric risk stratifications for both cardiovascular and non-cardiovascular outcomes.

Idiopathic Restrictive Cardiomyopathy in Children and Young Adults.

Idiopathic restrictive cardiomyopathy (IRC) is a rare condition characterized by reduced ventricular compliance. Children with IRC have poor outcomes with most patients proceeding to cardiac transplantation. We sought to analyze our institutional experience and assess contemporary outcomes for children with IRC. We reviewed the medical record for patients (<21 years old) evaluated for a primary diagnosis of IRC between 1975 and 2013 at our institution. Demographic, clinical, echocardiographic, and catheterization data were abstracted. The patients were divided into 2 groups comprising a historical cohort (HC) (diagnosis: 1975 to 1993, n = 8) and a contemporary cohort (CC) (diagnosis: 1994 to 2013, n = 12). Twenty children were identified with IRC (mean age at presentation 9.7 ± 6.5 years, 55% female). Mean length of follow-up was 6.5 ± 8.4 years (range 0.1 to 35.6 years). In the CC, 7 of 12 patients (58%) progressed to cardiac transplantation (mean age of 9 ± 4 years at transplant, mean interval from diagnosis of IRC: 1.5 ± 0.9 years). Overall survival was improved significantly in the CC compared with the HC (80% vs. 38%, p = 0.02), but transplantation free survival was no different between the CC and HC over 5 years (38% vs 38%, p = 0.65). In the CC, elevation of mitral valve Doppler E/e' ratio on echocardiography was associated with increased mortality (p = 0.01). In conclusion, IRC continues has a poor prognosis. Early referral for transplantation was associated with improved overall survival in the modern era. Patients with markedly elevated E/e' ratio may have increased risk of death.

Survival and prognostic factors in cats with restrictive cardiomyopathy: a review of 90 cases.

OBJECTIVES: Large studies focusing on restrictive cardiomyopathy (RCM) in the cat are scarce. The aims of this retrospective study were to describe epidemiological characteristics and to analyse prognostic factors affecting survival in cats with RCM. METHODS: The clinical archives of the Gran Sasso Veterinary Clinic (Milan, Italy) and of the cardiology unit of the Department of Veterinary Medicine (University of Milan, Italy) from 1997-2015 were reviewed for all cats diagnosed with RCM based on an echocardiographic examination (left atrial/biatrial enlargement, normal left ventricle wall thickness, normal or mildly decreased systolic function and restrictive left ventricle filling pattern with pulsed Doppler echocardiography). RESULTS: The study population comprised 90 cats (53 male, 37 female) with an echocardiographic diagnosis of RCM. Most were domestic shorthairs (n = 60) with a mean ± SD age of 10.0 ± 4.3 years and a median weight of 3.8 kg (interquartile range 3.2-5 kg). Most cats were symptomatic (n = 87). The most common clinical sign was respiratory distress (n = 75). Follow-up was available for 60 cats and the median survival time (MST) was 69 days (95% confidence interval [CI] 0-175 days). Cardiac-related death occurred in 50 cats. In the multivariate Cox analysis only respiratory distress showed a statistically significant effect on survival. The cats without respiratory distress showed an MST of 466 days (95% CI 0-1208); cats with respiratory distress showing an MST of 64 days (95% CI 8-120; P = 0.011). CONCLUSIONS AND RELEVANCE: RCM can be considered an end-stage condition associated with a poor prognosis, with few cats not showing clinical signs and surviving >1 year. Most cats died of cardiac disease within a very short time.

Antimalarial-induced cardiomyopathy: a systematic review of the literature.

Background Antimalarials (AMs) are widely used in the treatment of connective tissue diseases. Their main side effect is retinal damage, while heart disease has been described in isolated cases. The aim of this study is to systematically review the existing literature on AM-induced cardiomyopathy (AMIC). Methods The PubMed database was searched for heart biopsy-confirmed AMIC cases. Information on demographics, clinical presentation, concomitant AM-related toxicity, cardiological investigations, treatment and outcome were collected. Descriptive statistics were used. Results Forty-seven cases (42 females) were identified with a mean age at diagnosis 56.4 ± 12.6 and mean AM treatment duration 12.7 ± 8.2 years. Systemic lupus erythematosus ( n = 19) and rheumatoid arthritis ( n = 18) were the most common primary diseases. Clinical presentation was that of congestive heart failure in 77%, while eight patients presented with syncope (17%). Complete atrioventricular block was reported in 17 patients; 24 received a permanent pacemaker (51%). Impaired systolic function was detected in 52.8%, bi-ventricular hypertrophy in 51.4% and restrictive filling pattern of the left ventricle in 18 patients. Cardiac magnetic resonance showed late gadolinium enhancement in seven cases, with a non-vascular pattern in the interventricular septum. Cardiomyocyte vacuolation was reported in all cases; intravacuolar lamellar and curvilinear bodies were observed in 46 (98%) and 42 (89.4%) respectively. Mortality rate was 45% (18/40). Conclusion AMIC is a rare, probably under-recognized, complication of prolonged AM treatment. It presents as a hypertrophic, restrictive cardiomyopathy with or without conduction abnormalities. Early recognition and drug withdrawal are critical with a survival rate of almost 55%.

Clinical features of idiopathic restrictive cardiomyopathy: A retrospective multicenter cohort study over 2 decades.

Idiopathic restrictive cardiomyopathy (RCMP) has not been fully understood because this disease is difficult to diagnose. The present study aimed to assess the clinical profile and outcome of idiopathic RCMP from a multicenter cohort.This investigation is a retrospective study of consecutive patients with idiopathic RCMP at 10 centers in Korea between 1990 and 2010. We evaluated the clinical characteristics of the patients and prognostic factors associated with mortality using multivariate Cox proportional hazards regression analyses.The study included 53 patients (26 men, 49.1%). During a median follow-up of 1.7 years, 17 patients (32.1%) died and 5 patients (9.4%) received a heart transplant. The 5-year survival rate of the overall patients was 64.4% ±â€Š7.8%. In multivariable analyses, the predictors of mortality were tricuspid regurgitation (TR) ≥ moderate (hazard ratio [HR] 32.55, P < .001) and left ventricular end-diastolic diameter (LVEDD) (HR 0.85, P < .001).Idiopathic RCMP showed unfavorable prognosis. Advanced TR and lower LVEDD are independent adverse predictors of mortality in patients with idiopathic RCMP.

Heart and heart-liver transplantation in patients with hemochromatosis.

BACKGROUND: Hemochromatosis predisposes to dilated or restrictive cardiomyopathy which can progress to end-stage heart failure, requiring the use of advanced heart therapies including heart (HT) and heart liver (HLT) transplantation. Little is known about the characteristics and outcomes of these patients. METHODS AND RESULTS: We queried the United Network for Organ Sharing (UNOS) registry for all patients listed for HT or HLT for a diagnosis of 'hemochromatosis' between 1987 and 2014. Waitlist and post-transplantation outcomes were compared between patients with hemochromatosis (HT vs HLT) and other etiologies. Of the 81,356 adults listed for heart transplantation, 23 patients with hemochromatosis were identified (16 listed for HLT; and 7 listed for HT). Compared with other etiologies, HC patients were younger (39 vs 51years, p<0.0001), and more likely to need inotropes (56.5% vs 25.6%, p=0.003) and mechanical ventilation (13% vs 3.4%, p=0.041). Cumulative hazards of waitlist mortality or delisting were higher in hemochromatosis patients than for other etiologies of heart failure (p<0.001). There were 4 HT and 4 HLT during the study period. Post-transplantation, patients with HC had a 1- and 2-year cumulative survival of 88% and 75%, respectively. CONCLUSIONS: Both HT and HLT are viable options for patients with hemochromatosis. Patients with hemochromatosis are younger with increased wait-list mortality compared with other etiologies.

Does Survival on the Heart Transplant Waiting List Depend on the Underlying Heart Disease?

OBJECTIVES: The aim of this study was to identify differences in survival on the basis of type of heart disease while awaiting orthotopic heart transplantation (OHT). BACKGROUND: Patients with restrictive cardiomyopathy (RCM), congenital heart disease (CHD), or hypertrophic cardiomyopathy (HCM) may be at a disadvantage while awaiting OHT because they often are poor candidates for mechanical circulatory support and/or inotropes. METHODS: The study included all adults in the Scientific Registry of Transplant Recipients database awaiting OHT from 2004 to 2014, and outcomes were evaluated on the basis of type of heart disease. The primary endpoint was time to all-cause mortality, censored at last patient follow-up and time of transplantation. Multivariate Cox proportional hazards modeling was performed to evaluate survival by type of cardiomyopathy. RESULTS: There were 14,447 patients with DCM, 823 with RCM, 11,799 with ischemic cardiomyopathy (ICM), 602 with HCM, 964 with CHD, 584 with valvular disease, and 1,528 in the "other" category (including 1,216 for retransplantation). During median follow-up of 3.7 months, 4,943 patients died (1,253 women, 3,690 men). After adjusting for possible confounding variables including age, renal function, inotropes, mechanical ventilation, and mechanical circulatory support, the adjusted hazard ratios by diagnoses relative to DCM were 1.70 for RCM (95% confidence interval [CI]: 1.43 to 2.02), 1.10 for ICM (95% CI: 1.03 to 1.18), 1.23 for HCM (95% CI: 0.98 to 1.54), 1.30 for valvular disease (95% CI: 1.07 to 1.57), 1.37 for CHD (95% CI: 1.17 to 1.61), and 1.51 for "other" diagnoses (95% CI: 1.34 to 1.69). Sex was a significant modifier of mortality for ICM, RCM, and "other" diagnoses (p < 0.05 for interaction). CONCLUSIONS: In the United States, patients with RCM, CHD, or prior heart transplantation had a higher risk for death while awaiting OHT than patients with DCM, ICM, HCM, or valvular heart disease.

Heart Transplantation Outcomes in Radiation-Induced Restrictive Cardiomyopathy.

BACKGROUND: Some cancer therapies can cause advanced heart failure requiring heart transplantation. Although dilated cardiomyopathy is the most common phenotype, those who receive radiation may develop restrictive cardiomyopathy. The characteristics and transplantation outcomes patients with radiation-induced restrictive cardiomyopathy are not established. METHODS AND RESULTS: We used United Network for Organ Sharing registry to identify adults who were listed for heart transplantation between 2000 and 2015 for radiation-induced restrictive cardiomyopathy (RT-RCM) and compared their characteristics and transplant outcomes to restrictive cardiomyopathies of other etiologies (RCM) and all other patients listed for heart transplantation (others). Of 45,041 adults, 87 (0.2%) of transplantations were due to RT-RCM, 1049 (2.3%) were due to RCM, and there were 44,805 others. Compared with patients with RCM and other etiologies, those with RT-RCM were younger, less likely male, more likely to be white, listed as status 2, and were also more likely to have had previous cardiac surgeries. Posttransplant, patients with RT-RCM had longer lengths of stay and higher early mortality; 1-, 3-, and 5-year cumulative survival were as follows for RT-RCM (76%, 66%, 58%), RCM (88%, 79%, 73%; P = .025 compared with RT-RCM), and other etiologies (88%, 82%, 76%; P = .012 compared with RT-RCM). CONCLUSIONS: Patients with end-stage RT-RCM are predominantly younger females with previous cardiac surgeries. Posttransplantation survival in these patients appears to be lower than in those with other forms of restrictive cardiomyopathies and heart failure etiologies, mainly because of higher early postoperative mortality. Further studies are needed to confirm these findings.

Anterior Aortic Plane Systolic Excursion: A Novel Indicator of Transplant-Free Survival in Systemic Light-Chain Amyloidosis.

BACKGROUND: Anterior aortic plane systolic excursion (AAPSE) was evaluated in the present pilot study as a novel echocardiographic indicator of transplant-free survival in patients with systemic light-chain amyloidosis. METHODS: Eighty-nine patients with light-chain amyloidosis were included in the post-hoc analysis. A subgroup of 54 patients with biopsy-proven cardiac amyloid infiltration were compared with 41 healthy individuals to evaluate the discriminative ability of echocardiographic findings. AAPSE is defined as the systolic excursion of the anterior aortic margin. To quantify AAPSE, the M-mode cursor was placed on the aortic valve plane in parasternal long-axis view at end-diastole. Index echocardiography had been performed before chemotherapy. Median follow-up duration was 2.4 years. The primary combined end point was heart transplantation or overall death. RESULTS: Mean AAPSE was 14 ± 2 mm in healthy individuals (mean age=57 ± 10 years; 56% men; BMI=25 ± 4 kg/m2). AAPSE < 11 mm separated patients from age-, gender-, and BMI-matched control subjects with 93% sensitivity and 97% specificity. Median transplant-free survival of patients with AAPSE < 5 mm was 0.7 versus 4.8 years (P = .0001). AAPSE was an independent indicator of transplant-free survival in multivariate Cox regression (echocardiographic model: hazard ratio=0.72 [P = .03]; biomarker model: hazard ratio=0.62 [P = .0001]). Sequential regression analysis suggested incremental power of AAPSE as a marker of transplant-free survival. An ejection fraction-based model with an overall χ2 value of 22.8 was improved by the addition of log NT-proBNP (χ2 = 32.6, P < .005), troponin-T (χ2 = 39.6, P < .01), and AAPSE (χ2 = 54.0, P < .0001). CONCLUSIONS: AAPSE is suggested as an indicator of transplant-free survival in patients with systemic light-chain amyloidosis. AAPSE provided significant incremental value to established staging models.

Novel Phenotype-Genotype Correlations of Restrictive Cardiomyopathy With Myosin-Binding Protein C (MYBPC3) Gene Mutations Tested by Next-Generation Sequencing.

BACKGROUND: MYBPC3 dysfunctions have been proven to induce dilated cardiomyopathy, hypertrophic cardiomyopathy, and/or left ventricular noncompaction; however, the genotype-phenotype correlation between MYBPC3 and restrictive cardiomyopathy (RCM) has not been established. The newly developed next-generation sequencing method is capable of broad genomic DNA sequencing with high throughput and can help explore novel correlations between genetic variants and cardiomyopathies. METHODS AND RESULTS: A proband from a multigenerational family with 3 live patients and 1 unrelated patient with clinical diagnoses of RCM underwent a next-generation sequencing workflow based on a custom AmpliSeq panel, including 64 candidate pathogenic genes for cardiomyopathies, on the Ion Personal Genome Machine high-throughput sequencing benchtop instrument. The selected panel contained a total of 64 genes that were reportedly associated with inherited cardiomyopathies. All patients fulfilled strict criteria for RCM with clinical characteristics, echocardiography, and/or cardiac magnetic resonance findings. The multigenerational family with 3 adult RCM patients carried an identical nonsense MYBPC3 mutation, and the unrelated patient carried a missense mutation in the MYBPC3 gene. All of these results were confirmed by the Sanger sequencing method. CONCLUSIONS: This study demonstrated that MYBPC3 gene mutations, revealed by next-generation sequencing, were associated with familial and sporadic RCM patients. It is suggested that the next-generation sequencing platform with a selected panel provides a highly efficient approach for molecular diagnosis of hereditary and idiopathic RCM and helps build new genotype-phenotype correlations.

Role of ventricular assist therapy for patients with heart failure and restrictive physiology: Improving outcomes for a lethal disease.

BACKGROUND: Restrictive cardiomyopathy (RCM) patients have poor prognosis due to progressive heart failure characterized by impaired ventricular filling of either or both ventricles. The goal of this study was to evaluate the outcome of end-stage RCM patients after left ventricular assist device (LVAD) implantation and to determine factors that may be associated with improved survival. METHODS: This investigation is a retrospective study of prospectively collected data that include 28 consecutive patients with end-stage RCM who received continuous-flow LVADs at the Mayo Clinic, Rochester, Minnesota. Outcome was assessed by survival with LVAD support until heart transplantation or all-cause mortality. RESULTS: The mean follow-up time post-LVAD implantation was 448 ± 425 days. The mean hospitalization time was 29 ± 19 days and was complicated mainly by post-operative right ventricular (RV) failure requiring short-term medical support. The short-term in-hospital mortality was 14%. Ten patients underwent heart transplantation with 100% survival post-transplant during the follow-up period. One-year survival for patients with LVADs without transplantation was 64%, and was not significantly different between amyloidosis and non-amyloidosis patients. Larger left ventricle (LV) end-diastolic and end-systolic dimensions were significantly associated with improved survival rates (RR = 0.94 and 0.95, p < 0.05, respectively), and left ventricular end-diastolic diameter (LVEDD) ≤46 mm was associated with increased mortality post-LVAD implantation. CONCLUSIONS: LVAD is a feasible, life-saving therapy for end-stage heart failure related to RCM, especially as a bridge to transplant and in patients with larger LV dimensions.

Pediatric heart transplantation for congenital and restrictive cardiomyopathy.

BACKGROUND: Recent reports suggest worse outcomes in pediatric orthotopic heart transplantation (OHT) for congenital heart disease (CHD) and restrictive cardiomyopathy (RCM). We examined early outcomes in these diverse groups of patients in comparison with patients with dilatated cardiomyopathy (DCM). METHODS: From 2000 to 2011, 209 patients were included: 50 with CHD, 23 with RCM, and 136 with DCM. Early survival was studied, as was the occurrence of acute rejection, donor-specific antibodies (DSAs) and nondonor-specific antibodies (NSDAs), incidence of pulmonary hypertension (PHT), right ventricular failure (RVF), and the need for mechanical circulatory support (MCS). RESULTS: The incidence of preoperative PHT was greatest in the RCM group (χ(2)p = 0.0006); the requirement for mechanical support before OHT was greatest in patients with DCM. Thirty-day survival was 92.0%, 97.1%, and 100% for patients with CHD, DCM, and RCM respectively. The incidence of RVF was highest for patients with RCM (43.5%; versus CHD, 26.0%; versus DCM, 14.7%). One-year survival estimates for patients with CHD, DCM, and RCM were 92.0%, 97.8%, and 82.6%, respectively (log-rank p = 0.165). Multivariable analysis revealed 4 significant risk factors for mortality: age, incidence of acute rejection, preoperative PHT, and the presence of NDSAs. The occurrence of DSAs was similar, although there was a significantly higher incidence of NDSAs in the CHD and RCM groups (36.0% and 30.4%, respectively, versus 14.0% in the DCM group; χ(2)p = 0.0024). CONCLUSIONS: Equivalent outcomes are achievable in pediatric OHT despite marked heterogeneity in anatomic and physiologic complexity in recipients. Physiologic factors such as PHT are likely to be more important than anatomic complexities in determining survival. The potential relevance of NDSAs warrants further investigation.

[The donor's heart 22 years after the orthotopic transplantation].

The orthotopic heart transplantation is an acknowledge method for the treatment of cardiomyopathies of various etiology. Specific vasculopathy of the transplanted heart is considered to be a significant problem of the long-term postoperative period and serves the reason of low 10-years survival rates (not more then 50%). The issue unites the experience of follow-up and intravital electronic microscopy of transplantated heart's biopsies from 20 patients. Previously unknown data can help the clarification of posttransplantational cardiomyopathy.

Outcomes of adults with restrictive cardiomyopathy after heart transplantation.

BACKGROUND: Restrictive cardiomyopathy (RCM) represents a spectrum of disorders with a common physiology but divergent etiologies. RCM commonly leads to progressive heart failure and the need for heart transplantation (HTx). Pediatric RCM is a more homogeneous disorder with post-HTx outcomes comparable to those for non-RCM patients. However, post-HTx outcomes in adult RCM patients have not been studied to date. METHODS: Demographic, clinical and survival outcomes of 38,190 adult HTx-only recipients from 1987 to 2010 were acquired from the registry of the United Network of Organ Sharing. The study population included 544 RCM patients (1.4%) and 37,646 non-RCM patients (98.6%). RCM diagnoses included idiopathic (n = 227, 42%), amyloid (n = 142, 26%), sarcoid (n = 81, 15%), radiation/chemotherapy (XRT) (n = 35, 6%) and other (n = 59, 11%). RESULTS: Follow-up began at the time of HTx (74±64 months). During the follow-up period, 224 (41%) patients in the RCM group died, whereas 18,791 (50%) in the non-RCM group died. Crude 1-, 5- and 10-year survival for RCM patients was 84%, 66% and 45%, and for non-RCM patients was 85%, 70% and 50%, respectively. The overall unadjusted hazard ratio of RCM vs non-RCM for all-cause mortality was 1.07 (confidence interval [CI] 0.93 to 1.22). Multivariate Cox proportional hazards regression analysis yielded a hazard ratio of 1.06 (CI 0.91 to 1.25). RCM subgroup analysis showed decreased survival at 1, 5 and 10 years in the XRT (71%, 47% and 32%) and amyloid (79%, 47% and 28%) patient groups. The unadjusted hazard ratio for the XRT and amyloid subgroups vs RCM for all-cause mortality was 1.81 (p = 0.002) and 1.85 (p = 0.0004), respectively. CONCLUSIONS: Outcomes for RCM patients post-HTx are comparable to those of non-RCM patients. However, RCM subgroup analysis suggests increased mortality for XRT and amyloid subgroups. Further analysis is warranted to understand the contributing factors.

Current outcomes in US children with cardiomyopathy listed for heart transplantation.

BACKGROUND: Previous studies have reported worse outcomes in children with nondilated cardiomyopathy (CMP) listed for heart transplant compared with children with dilated CMP. We sought to compare wait-list and posttransplant outcomes in these groups in the current era. METHODS AND RESULTS: We analyzed all children <18 years of age with a diagnosis of CMP listed for heart transplant in the United States between July 2004 and December 2010. Multivariable risk factors for death on the wait-list (or becoming too sick to transplant) and posttransplant graft loss (median follow-up 2 years) were assessed using Cox models. Of the 1436 children analyzed, 1197 (83%) had dilated CMP and 239 (17%) had nondilated CMP (167 restrictive CMP, 72 hypertrophic CMP). In adjusted analysis, children with nondilated CMP were at higher risk of wait-list mortality only if they were on a ventilator support at listing (hazard ratio, 2.3; CI, 1.2-4.5). The risk was similar among children not on a ventilator support (hazard ratio, 0.6; CI, 0.3-1.1). Posttransplant 30-day and 1-year survival was 98% and 94%, respectively, in children with dilated CMP versus 95% and 89%, respectively, in children with nondilated CMP (P=0.17, log-rank test). In adjusted analysis, the risk of posttransplant graft loss was higher in nondilated CMP (hazard ratio, 1.8; CI, 1.2-2.7) versus dilated CMP. CONCLUSIONS: The increased risk of wait-list mortality in children with nondilated CMP is limited to those on ventilator support at listing. Although the risk of graft loss is modestly higher in children with nondilated forms of CMP, their short-term transplant outcomes are good.

Outcomes of restrictive cardiomyopathy in childhood and the influence of phenotype: a report from the Pediatric Cardiomyopathy Registry.

BACKGROUND: Restrictive cardiomyopathy (RCM) has been associated with poor prognosis in childhood. The goal of the present analysis was to use the Pediatric Cardiomyopathy Registry to analyze outcomes of childhood RCM, with a focus on the impact of phenotype comparing pure RCM with cases that have additional features of hypertrophic cardiomyopathy (HCM). METHODS AND RESULTS: We analyzed the Pediatric Cardiomyopathy Registry database (1990-2008; N=3375) for cases of RCM. Cases were defined as pure when RCM was the only assigned diagnosis. Additional documentation of HCM at any time was used as the criterion for RCM/HCM phenotype. RCM accounted for 4.5% of cases of cardiomyopathy. In 101 (66%), pure RCM was diagnosed; in 51 (34%), there was a mixed phenotype. Age at diagnosis was not different between groups, but 10% of the pure RCM group was diagnosed in infancy versus 24% of the RCM/HCM group. Freedom from death was comparable between groups with 1-, 2-, and 5-year survival of RCM 82%, 80%, and 68% versus RCM/HCM 77%, 74%, and 68%. Transplant-free survival was 48%, 34%, and 22% and 65%, 53%, and 43%, respectively (P=0.011). Independent risk factors at diagnosis for lower transplant-free survival were heart failure (hazard ratio 2.20, P=0.005), lower fractional shortening z score (hazard ratio 1.12 per 1 SD decrease in z score, P=0.014), and higher posterior wall thickness in the RCM/HCM group only (hazard ratio 1.32, P<0.001). Overall, outcomes were worse than for all other forms of cardiomyopathy. CONCLUSIONS: Transplant-free survival is poor for RCM in childhood. Survival is independent of phenotype; however, the RCM/HCM phenotype has significantly better transplant-free survival. CLINICAL TRIALS REGISTRATION: URL: http://www.clinicaltrials.gov. Unique Identifier: NCT00005391.

Clinical experience with Berlin Heart Excor in pediatric patients in Argentina: 1373 days of cardiac support.

The objective of this study was to describe our experience (1373 days of support) with the Berlin Heart Excor (BH) ventricular-assist device (VAD) as bridging to cardiac transplantation in pediatric patients with end-stage cardiomyopathy. This study involved a retrospective observational cohort. Records of patients supported with the BH VAD were reviewed. Data regarding age, sex, weight, diagnosis, preoperative condition, single versus biventricular support, morbidity, and mortality were collected. Criteria for single versus biventricular support and intensive care unit management were registered. The procedure was approved by our Institutional Ethics Committee, and informed consent was obtained. Between March 2006 and March 2010, 12 patients with diagnosis of dilated (n = 10) and restrictive (n = 2) cardiomyopathy were supported. Median age was 56.6 months (range 20.1-165.9); mean weight was 18.3 kg (range 8.5-45); and nine patients were female. Every patient presented with severe heart failure refractory to pharmacological therapy. Biventricular support was necessary in four patients. Nine patients underwent heart transplantation. No child was weaned off the BH VAD because of myocardial recovery. Mean length of support was 73 days (range 3-331), and the total number of days of support was 1373. Three patients had fatal complications: 2 had thrombo-hemorrhagic stroke leading to brain death, and one had refractory vasoplegic shock. The BH VAD is a useful and reasonable safe device for cardiac transplantation bridging in children with end-stage heart failure. Team experience resulted in less morbidity and mortality, and time for implantation, surgical procedure, anticoagulation monitoring, and patient care improved.

Elective cardiac retransplantation: a viable option that can be repeated.

OBJECTIVE: Our hypothesis is that cardiac retransplantation is a viable option for selected recipients. Furthermore, in some patients multiple retransplantations are reasonable. METHODS: We studied 23 patients who had all received an elective second, third, or fourth cardiac transplant over a 25-year period. Comparisons were made with 792 primary transplantations. Subsequent retransplantations (third and fourth time) were elective and included in the evaluation. RESULTS: Twenty-three patients electively received a second, 4 a third, and 1 a fourth transplant for coronary vasculopathy or chronic graft failure. Sixteen (70%) patients were men, and 7 (30%) were women. Median survival in years for primary cardiac recipients was 10.7 years; for a second transplantation, median survival from the date of retransplantation was 9.3 years. Average age at the time of first transplantation was 47.8 years, and it was 44.3 years at the time of second transplantation. No significant difference was noted in Kaplan-Meier survival curves between patients undergoing primary transplantation and elective retransplantation. Survival at 1 year for patients undergoing a first transplantation was 88.8%, and it was 81.8% for patients undergoing retransplantation. Patient survival at 10 years was nearly identical for patients undergoing first-time transplantation and those undergoing retransplantation (58%). All 5 third- and fourth-time transplant recipients survived. CONCLUSIONS: Cardiac retransplantation is a reasonable option for elective recipients with coronary vasculopathy or chronic graft failure. Survival for groups undergoing primary transplantation and retransplantation is similar. Careful selection of this small group of cardiac recipients (3% of the total) might be the key to success.