Outcomes after surgical ventricular restoration for ischemic cardiomyopathy.

OBJECTIVE: The study objective was to evaluate the short- and long-term outcomes of patients with ischemic cardiomyopathy after surgical ventricular restoration and to identify risk factors related to poor results. METHODS: Between August 2002 and April 2016, 62 patients affected by ischemic cardiomyopathy underwent surgical left ventricular restoration at our unit. Patients' mean age at operation was 63 years (39-79 years). Mean ejection fraction was 29.6%. The Surgical Treatment for Ischemic Heart Failure trial criteria have been used as indications for surgery. Fifty-seven patients (91%) received surgical myocardial revascularization. Mitral valve repair was performed in 39 patients (63%). The surgical technique consisted of the classic Dor operation or a different approach reducing the equatorial diameter of the left ventricle and avoiding the use of a patch. The data were analyzed retrospectively for perioperative results and short- and long-term clinical outcomes. RESULTS: One patient died of noncardiac causes within 30 days (1.6%). All-cause death occurred in 36 patients (58%) during follow-up (0.6-14.7 years; median follow-up time, 7.02 years), of whom 15 died of cardiac causes. Age, need for preoperative intra-aortic balloon pump, reduction less than 35% of postoperative left ventricular end-diastolic and end-systolic volumes, type of surgical technique, and ejection fraction less than 25% were identified as risk factors for late cardiac mortality. Perioperative levosimendan administration and presence of preoperative moderate to severe mitral regurgitation influenced early and intermediate-term outcomes, but no statistical relevance on long-term results was demonstrated. CONCLUSIONS: Patients with ischemic dilative cardiomyopathy have favorable short- and long-term outcomes after ventricular restoration. Age, preoperative ejection fraction less than 25%, inadequate left ventricular surgical reverse remodeling, and type of surgical technique negatively affect long-term survival.

Pathogenic Variants Associated With Dilated Cardiomyopathy Predict Outcome in Pediatric Myocarditis.

BACKGROUND: Myocarditis is one of the most common causes leading to heart failure in children and a possible genetic background has been postulated. We sought to characterize the clinical and genetic characteristics in patients with myocarditis ≤18 years of age to predict outcome. METHODS: A cohort of 42 patients (Genetics in Pediatric Myocarditis) with biopsy-proven myocarditis underwent genetic testing with targeted panel sequencing of cardiomyopathy-associated genes. Genetics in Pediatric Myocarditis patients were divided into subgroups according to the phenotype of dilated cardiomyopathy (DCM) at presentation, resulting in 22 patients without DCM (myocarditis without phenotype of DCM) and 20 patients with DCM (myocarditis with phenotype of DCM). RESULTS: Myocarditis with phenotype of DCM patients (median age 1.4 years) were younger than myocarditis without phenotype of DCM patients (median age 16.1 years; P<0.001) and were corresponding to heart failure-like and coronary syndrome-like phenotypes, respectively. At least one likely pathogenic/pathogenic variant was identified in 9 out of 42 patients (22%), 8 of them were heterozygous, and 7 out of 9 were in myocarditis with phenotype of DCM. Likely pathogenic/pathogenic variants were found in genes validated for primary DCM (BAG3, DSP, LMNA, MYH7, TNNI3, TNNT2, and TTN). Rare variant enrichment analysis revealed significant accumulation of high-impact disease variants in myocarditis with phenotype of DCM versus healthy individuals (P=0.0003). Event-free survival was lower (P=0.008) in myocarditis with phenotype of DCM patients compared with myocarditis without phenotype of DCM and primary DCM. CONCLUSIONS: We report heterozygous likely pathogenic/pathogenic variants in biopsy-proven pediatric myocarditis. Myocarditis patients with DCM phenotype were characterized by early-onset heart failure, significant enrichment of likely pathogenic/pathogenic variants, and poor outcome. These phenotype-specific and age group-specific findings will be useful for personalized management of these patients. Genetic evaluation in children newly diagnosed with myocarditis and DCM phenotype is warranted.

Stem cell therapy for dilated cardiomyopathy.

BACKGROUND: Stem cell therapy (SCT) has been proposed as an alternative treatment for dilated cardiomyopathy (DCM), nonetheless its effectiveness remains debatable. OBJECTIVES: To assess the effectiveness and safety of SCT in adults with non-ischaemic DCM. SEARCH METHODS: We searched CENTRAL in the Cochrane Library, MEDLINE, and Embase for relevant trials in November 2020. We also searched two clinical trials registers in May 2020. SELECTION CRITERIA: Eligible studies were randomized controlled trials (RCT) comparing stem/progenitor cells with no cells in adults with non-ischaemic DCM. We included co-interventions such as the administration of stem cell mobilizing agents. Studies were classified and analysed into three categories according to the comparison intervention, which consisted of no intervention/placebo, cell mobilization with cytokines, or a different mode of SCT. The first two comparisons (no cells in the control group) served to assess the efficacy of SCT while the third (different mode of SCT) served to complement the review with information about safety and other information of potential utility for a better understanding of the effects of SCT. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all references for eligibility, assessed trial quality, and extracted data. We undertook a quantitative evaluation of data using random-effects meta-analyses. We evaluated heterogeneity using the I² statistic. We could not explore potential effect modifiers through subgroup analyses as they were deemed uninformative due to the scarce number of trials available. We assessed the certainty of the evidence using the GRADE approach. We created summary of findings tables using GRADEpro GDT. We focused our summary of findings on all-cause mortality, safety, health-related quality of life (HRQoL), performance status, and major adverse cardiovascular events. MAIN RESULTS: We included 13 RCTs involving 762 participants (452 cell therapy and 310 controls). Only one study was at low risk of bias in all domains. There were many shortcomings in the publications that did not allow a precise assessment of the risk of bias in many domains. Due to the nature of the intervention, the main source of potential bias was lack of blinding of participants (performance bias). Frequently, the format of the continuous data available was not ideal for use in the meta-analysis and forced us to seek strategies for transforming data in a usable format. We are uncertain whether SCT reduces all-cause mortality in people with DCM compared to no intervention/placebo (mean follow-up 12 months) (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.54 to 1.31; I² = 0%; studies = 7, participants = 361; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection in people with DCM (data could not be pooled; studies = 7; participants = 361; very low-certainty evidence). We are uncertain whether SCT improves HRQoL (standardized mean difference (SMD) 0.62, 95% CI 0.01 to 1.23; I² = 72%; studies = 5, participants = 272; very low-certainty evidence) and functional capacity (6-minute walk test) (mean difference (MD) 70.12 m, 95% CI -5.28 to 145.51; I² = 87%; studies = 5, participants = 230; very low-certainty evidence). SCT may result in a slight functional class (New York Heart Association) improvement (data could not be pooled; studies = 6, participants = 398; low-certainty evidence). None of the included studies reported major adverse cardiovascular events as defined in our protocol. SCT may not increase the risk of ventricular arrhythmia (data could not be pooled; studies = 8, participants = 504; low-certainty evidence). When comparing SCT to cell mobilization with granulocyte-colony stimulating factor (G-CSF), we are uncertain whether SCT reduces all-cause mortality (RR 0.46, 95% CI 0.16 to 1.31; I² = 39%; studies = 3, participants = 195; very low-certainty evidence). We are uncertain whether SCT increases the risk of procedural complications associated with cells injection (studies = 1, participants = 60; very low-certainty evidence). SCT may not improve HRQoL (MD 4.61 points, 95% CI -5.62 to 14.83; studies = 1, participants = 22; low-certainty evidence). SCT may improve functional capacity (6-minute walk test) (MD 140.14 m, 95% CI 119.51 to 160.77; I² = 0%; studies = 2, participants = 155; low-certainty evidence). None of the included studies reported MACE as defined in our protocol or ventricular arrhythmia. The most commonly reported outcomes across studies were based on physiological measures of cardiac function where there were some beneficial effects suggesting potential benefits of SCT in people with non-ischaemic DCM. However, it is unclear if this intermediate effects translates into clinical benefits for these patients. With regard to specific aspects related to the modality of cell therapy and its delivery, uncertainties remain as subgroup analyses could not be performed as planned, making it necessary to wait for the publication of several studies that are currently in progress before any firm conclusion can be reached. AUTHORS' CONCLUSIONS: We are uncertain whether SCT in people with DCM reduces the risk of all-cause mortality and procedural complications, improves HRQoL, and performance status (exercise capacity). SCT may improve functional class (NYHA), compared to usual care (no cells). Similarly, when compared to G-CSF, we are also uncertain whether SCT in people with DCM reduces the risk of all-cause mortality although some studies within this comparison observed a favourable effect that should be interpreted with caution. SCT may not improve HRQoL but may improve to some extent performance status (exercise capacity). Very low-quality evidence reflects uncertainty regarding procedural complications. These suggested beneficial effects of SCT, although uncertain due to the very low certainty of the evidence, are accompanied by favourable effects on some physiological measures of cardiac function. Presently, the most effective mode of administration of SCT and the population that could benefit the most is unclear. Therefore, it seems reasonable that use of SCT in people with DCM is limited to clinical research settings. Results of ongoing studies are likely to modify these conclusions.

HE4 Predicts Progressive Fibrosis and Cardiovascular Events in Patients With Dilated Cardiomyopathy.

Background Cardiac fibrosis plays a crucial role in the pathogenesis of dilated cardiomyopathy (DCM). HE4 (human epididymis protein 4) is a secretory protein expressed in activated fibroblasts that exacerbates tissue fibrosis. In the present study, we investigated the clinical utility of HE4 measurement in patients with DCM and its pathophysiological role in preclinical experiments in vivo and in vitro. Methods and Results We measured serum HE4 levels of 87 patients with DCM. Endomyocardial biopsy expressed severe fibrosis only in the high HE4 group (P<0.0001). Echocardiography showed that left ventricular end-diastolic diameter tends to decrease over time (58±7.3 to 51±6.6 mm; P<0.0001) in the low HE4 group (<59.65 pmol/L [median value]). HE4 was significantly associated with risk reduction of mortality and cardiovascular hospitalization in multivariate Cox model. In vivo, HE4 was highly expressed in kidney and lung tissue of mouse, and scarcely expressed in heart. In genetically induced DCM mouse model, HE4 expression increased in kidney but not in heart and lung. In vitro, supernatant from HE4-transfected human embryonic kidney 293T cells enhanced transdifferentiation of rat neonatal fibroblasts and increased expression of fibrosis-related genes, and this was accompanied by the activation of extracellular signal-regulated kinase signaling in cardiac fibroblasts. Treatment with an inhibitor of upstream signal of extracellular signal-regulated kinase or a neutralizing HE4 antibody canceled the profibrotic properties of HE4. Conclusions HE4 functions as a secretory factor, activating cardiac fibroblasts, thereby inducing cardiac interstitial fibrosis. HE4 could be a promising biomarker for assessing ongoing fibrosis and a novel therapeutic target in DCM. Registration URL: https://upload.umin.ac.jp/cgi-open-bin/ctr; Unique identifier: UMIN000043062.

Association of Left Ventricular Systolic Dysfunction Among Carriers of Truncating Variants in Filamin C With Frequent Ventricular Arrhythmia and End-stage Heart Failure.

Importance: Truncating variants in the gene encoding filamin C (FLNCtv) are associated with arrhythmogenic and dilated cardiomyopathies with a reportedly high risk of ventricular arrhythmia. Objective: To determine the frequency of and risk factors associated with adverse events among FLNCtv carriers compared with individuals carrying TTN truncating variants (TTNtv). Design, Setting, and Participants: This cohort study recruited 167 consecutive FLNCtv carriers and a control cohort of 244 patients with TTNtv matched for left ventricular ejection fraction (LVEF) from 19 European cardiomyopathy referral units between 1990 and 2018. Data analyses were conducted between June and October, 2020. Main Outcomes and Measures: The primary end point was a composite of malignant ventricular arrhythmia (MVA) (sudden cardiac death, aborted sudden cardiac death, appropriate implantable cardioverter-defibrillator shock, and sustained ventricular tachycardia) and end-stage heart failure (heart transplant or mortality associated with end-stage heart failure). The secondary end point comprised MVA events only. Results: In total, 167 patients with FLNCtv were studied (55 probands [33%]; 89 men [53%]; mean [SD] age at baseline evaluation, 43 [18] years). For a median follow-up of 20 months (interquartile range, 7-60 months), 29 patients (17.4%) reached the primary end point (19 patients with MVA and 10 patients with end-stage heart failure). Eight (44%) arrhythmic events occurred among individuals with baseline mild to moderate left ventricular systolic dysfunction (LVSD) (LVEF = 36%-49%). Univariable risk factors associated with the primary end point included proband status, LVEF decrement per 10%, ventricular ectopy (≥500 in 24 hours) and myocardial fibrosis detected on cardiac magnetic resonance imaging. The LVEF decrement (hazard ratio [HR] per 10%, 1.83 [95% CI, 1.30-2.57]; P < .001) and proband status (HR, 3.18 [95% CI, 1.12-9.04]; P = .03) remained independent risk factors on multivariable analysis (excluding myocardial fibrosis and ventricular ectopy owing to case censoring). There was no difference in freedom from MVA between FLNCtv carriers with mild to moderate or severe (LVEF ≤35%) LVSD (HR, 1.29 [95% CI, 0.45-3.72]; P = .64). Carriers of FLNCtv with impaired LVEF at baseline evaluation (n = 69) had reduced freedom from MVA compared with 244 TTNtv carriers with similar baseline LVEF (for mild to moderate LVSD: HR, 16.41 [95% CI, 3.45-78.11]; P < .001; for severe LVSD: HR, 2.47 [95% CI, 1.04-5.87]; P = .03). Conclusions and Relevance: The high frequency of MVA among patients with FLNCtv with mild to moderate LVSD suggests that higher LVEF values than those currently recommended should be considered for prophylactic implantable cardioverter-defibrillator therapy in FLNCtv carriers.

Measurement of multiple cytokines for discrimination and risk stratification in patients with Chagas' disease and idiopathic dilated cardiomyopathy.

Chagas' disease (CD), caused by the hemoflagellate protozoan, Trypanosoma cruzi, is endemic in most countries of Latin America. Heart failure (HF) is often a late manifestation of chronic CD, and is associated with high morbidity and mortality. Inflammatory processes mediated by cytokines play a key role in the pathogenesis and progression of CD. Keeping in view the inflammatory nature of CD, this study investigated the possible role of 21 different inflammatory cytokines as biomarkers for prediction and prognosis of CD. The plasma concentration of these cytokines was measured in a group of patients with CD (n = 94), and then compared with those measured in patients with dilated cardiomyopathy (DCM) from idiopathic causes (n = 48), and with control subjects (n = 25). Monovariately, plasma levels of cytokines such as stem cell growth factor beta (SCGF beta), hepatocyte growth factor (HGF), monokine induced by interferon gamma (CXCL9), and macrophage inhibitory factor (MIF) were significantly increased in CD patients with advanced HF compared to control group. None of the cytokines could demonstrate any prognostic potency in CD patients, and only MIF and stromal derived factor-1 alpha (CXCL12) showed significance in predicting mortality and necessity for heart transplant in DCM patients. However, multivariate analysis prognosticated a large proportion of CD and DCM patients. In CD patients, HGF and Interleukin-12p40 (IL-12p40) together separated 81.9% of 3-year survivors from the deceased, while in DCM patients, CXCL12, stem cell factor (SCF), and CXCL9 together discriminated 77.1% of survivors from the deceased. The significant increase in plasma concentrations of cytokines such as HGF and CXCL9 in CD patients, and the ability of these cytokines to prognosticate a large proportion of CD and DCM patients multivariately, encourages further studies to clarify the diagnostic and prognostic potential of cytokines in such patients.

Efficacy of Pulmonary Artery Pulsatility Index as a Measure of Right Ventricular Dysfunction in Stable Phase of Dilated Cardiomyopathy.

BACKGROUND: Right ventricular dysfunction (RVD) in the setting of left ventricular (LV) myocardial damage is a major cause of morbidity and mortality, and the pulmonary artery pulsatility index (PAPi) is a novel hemodynamic index shown to predict RVD in advanced heart failure. However, it is unknown whether PAPi can predict the long-term prognosis of dilated cardiomyopathy (DCM) even in the mild to moderate phase. This study aimed to assess the ability of PAPi to stratify DCM patients without severe symptoms.Methods and Results:Between April 2000 and March 2018, a total of 162 DCM patients with stable symptoms were evaluated, including PAPi, and followed up for a median of 4.91 years. The mean age was 50.9±12.6 years and the mean LV ejection fraction (EF) was 30.5±8.3%. When divided into 2 groups based on median value of PAPi (low, L-PAPi [<3.06] and high, H-PAPi [≥3.06]), even though there were no differences in B-type natriuretic peptide or pulmonary vascular resistance, the probability of cardiac event survival was significantly higher in the L-PAP than in the H-PAP group by Kaplan-Meier analysis (P=0.018). Furthermore, Cox's proportional hazard regression analysis revealed that PAPi was an independent predictor of cardiac events (hazard ratio: 0.782, P=0.010). CONCLUSIONS: Even in patients identified with DCM in the mild to moderate phase, PAPi may help stratify DCM and predict cardiac events.

Serum Chemerin Predicts the Prognosis of Patients With Dilated Cardiomyopathy.

BACKGROUND: Chemerin is a newly discovered adipokine, which has been reported to be associated with the presence of dilated cardiomyopathy (DCM). The present study aims to evaluate the prognostic value of serum chemerin in patients with DCM. METHODS: A total of 214 patients with DCM was recruited and divided into 4 groups, according to quartiles of chemerin levels. Kaplan-Meier analysis was conducted to compare the survival rates among patients with different levels of chemerin, using the log-rank test. Multivariate Cox regression analysis was performed to assess the association of serum chemerin levels and occurrence of major adverse cardiac events (MACEs), including cardiac mortality, stroke and myocardial infarction. RESULTS: The Kaplan-Meier survival analysis indicated that patients with higher concentration of chemerin had shorter event-free survivals for MACEs (P < .01). Cox regression analysis showed that chemerin was a significant predictor of MACEs (Quartile 3 versus Quartile 1: HR=1.79, 95% CI: 1.31-2.79; Quartile 4 versus Quartile 1: HR=2.87, 95% CI: 1.79-4.25) and all-cause death (Quartile 3 versus Quartile 1: HR=1.56, 95% CI: 1.20-2.42; Quartile 4 versus Quartile 1: HR=2.28, 95% CI: 1.52-3.96) after adjusting for potential risk factors. CONCLUSION: Serum chemerin should be a potential prognostic indicator in patients with DCM.

Left Ventricular Stroke Work Index Associated With Outcome After Mitral Valve Surgery for Functional Regurgitation in Nonischemic Dilated Cardiomyopathy.

The indications for mitral valve surgery in patients with advanced nonischemic dilated cardiomyopathy and functional mitral regurgitation are still unclear. We reviewed our experience of mitral valve surgery in such patients and explored factors that were predictive of outcomes. Fifty-three consecutive patients with nonischemic dilated cardiomyopathy and an ejection fraction <35% who underwent mitral valve surgery were reviewed. Thirty five patients (66%) suffered all-cause death or underwent admission for heart failure or left ventricular assist device implantation after mitral valve surgery during follow-up (37 ± 27 months); freedom from these events at 3 years was 45%. Mitral valve surgery significantly reduced left ventricular volume (P < 0.01) and pulmonary vascular resistance (P < 0.01) in survivors. New York Heart Association functional class also improved significantly (P < 0.01) at 1 year after surgery. By multivariate analysis, preoperative left ventricular stroke work index (P < 0.04) was the sole significant predictor of composite outcomes including all-cause mortality, admission for heart failure or left ventricular assist device implantation after mitral valve surgery, with a cut-off value of 25.9 g-m/m2/beat. A higher tethering height (≥11 mm, P < 0.01) was a significant predictive factor for mitral regurgitation recurrence (P = 0.02). Mitral valve surgery for significant functional mitral regurgitation associated with nonischemic cardiomyopathy is still challenging. However, thorough hemodynamic investigations prior to surgery could provide useful indications regarding mitral valve surgery in these patients, contributing to an improvement in their clinical outcomes.

Pediatric ventricular assist device therapy for advanced heart failure-Hong Kong experience.

Ventricular assist devices (VADs) are life-saving options for children with heart failure unresponsive to medical therapy as a bridge to transplantation or cardiac recovery. We present a retrospective review of 13 consecutive children who underwent implantation of VAD between 2001 and 2018 in our center. The median age was 12 years (1-17 years), weight was 45 kg (10-82 kg). Etiologies of heart failure were dilated cardiomyopathy (CMP) (n = 8), myocarditis (n = 2), ischemic CMP (n = 1), restrictive CMP (n = 1) and congenital heart disease (n = 1). Pre-implantation ECMO was used in 5, mechanical ventilation in 4, renal replacement therapy in 2 and IABP in 1. Devices used were: Berlin Heart EXCOR left VAD (LVAD), biventricular VAD (BIVAD) (n = 5, 2), CentriMag LVAD, BIVAD (n = 1, 2), HeartWare (n = 2), HeartMate II (n = 1). Median duration of support was 45 days (3-823 days). Overall survival was 85%. Four patients were successfully bridged to transplantation, 2 died while on a device, 4 remain on support and 3 were weaned from VAD. Late death occurred in 2 transplanted patients. Complications included bleeding requiring reoperation in 1, neurologic events in 3, driveline infections and pericardial effusion in 2 each. In one patient, CentriMag BIVAD provided support for 235 days, which is longest reported duration on such a VAD in the Asia Pacific region. Survival for pediatric patients of all ages is excellent using VADs. Given the severity of illness in these children morbidity and mortality is acceptable. VADs could potentially be used as a long-term bridge to transplantation in view of the donor shortage in the pediatric population.

Genetic determinants of responsiveness to mesenchymal stem cell injections in non-ischemic dilated cardiomyopathy.

BACKGROUND: Non-ischemic dilated cardiomyopathy (NIDCM) responds variably to intramyocardial injection of mesenchymal stem cells (MSCs). We hypothesized that NIDCM genotype may influence responsiveness to MSC therapy and performed genotyping on all patients in the POSEIDON-DCM trial. METHODS: POSEIDON-DCM patients (n = 34) underwent genetic sequence analysis and deletion/duplication testing. The results were classified as positive for pathological variants (PV+; n = 8), negative for any variants (V-; n = 6), or as variants of uncertain significance (VUS; n = 20). All outcomes of therapy were analysed for each category of genetic results. FINDINGS: The 3 groups were indistinguishable at baseline with regard to ejection fraction (EF), demographics, medication use, or functional parameters. V- patients had an increase in EF at 12 months: +13.6% (IQR = +7.8%; +20.5%; p = 0.002), compared with VUS (+6.5%; IQR = +0.9%, +11.1%; p = 0.005) and PV+(-5.9%; IQR = -12.7%, +1.0; p = 0.2; p = 0.01 between groups). Six-minute walk distance improved in V- patients, but not in VUS and PV+. V- patients improved MLHFQ, compared to the other 2 groups, which did not improve over time. EPCCFUs increased by 9.7 ±â€¯1.9 in V- (p = 0.009) compared to VUS and PV+ patients. V- patients had one-year survival (100%) compared with VUS (85%) and PV+ (40%; p = 0.015 log-rank). Similarly, MACE rates were lower in V- (0%) than PV+ (61.9%) or VUS (42.2%; p = 0.021 log-rank). INTERPRETATION: Our findings support the concept that the genetic profile of NIDCM patients plays a role in responsiveness to MSC therapy, with V- patients more likely to benefit and the converse for PV+. This observation emphasizes the need for further genetic studies, because of important implications for the management of NIDCM syndromes.

Efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy: a systematic appraisal and meta-analysis.

BACKGROUND: The clinical significance of stem cell therapy in the treatment of dilated cardiomyopathy remains unclear. This systemic appraisal and meta-analysis aimed to assess the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. After searching the PubMed, Embase, and Cochrane library databases until November 2017, we conducted a meta-analysis to evaluate the efficacy and safety of stem cell therapy in patients with dilated cardiomyopathy. METHODS: The weighted mean difference (WMD), standard mean difference (SMD), relative risk (RR), and 95% confidence interval (CI) were summarized in this meta-analysis. Both fixed effects and random effects models were used to combine the data. Sensitivity analyses were conducted to evaluate the impact of an individual dataset on the pooled results. RESULTS: A total of eight randomized controlled trials, which involved 531 participants, met the inclusion criteria in this systematic appraisal and meta-analysis. Our meta-analysis showed that stem cell therapy improves left ventricular ejection fraction (SMD = 1.09, 95% CI 0.29 to 1.90, I2 = 92%) and reduces left ventricular end-systolic volume (SMD = - 0.36, 95% CI - 0.61 to - 0.10, I2 = 20.5%) and left ventricular end-diastolic chamber size (SMD = - 0.48, 95% CI - 0.89 to - 0.07, I2 = 64.8%) in patients with dilated cardiomyopathy. However, stem cell therapy has no effect on mortality (RR = 0.72, 95% CI 0.50 to 1.02, I2 = 30.2%) and 6-min-walk test (WMD = 51.52, 95% CI - 24.52 to 127.55, I2 = 94.8%). CONCLUSIONS: This meta-analysis suggests that stem cell therapy improves left ventricular ejection fraction and reduces left ventricular end-systolic volume and left ventricular end-diastolic chamber size in patients with dilated cardiomyopathy. However, future well-designed large studies might be necessary to clarify the effect of stem cell therapy in patients with dilated cardiomyopathy.

ECG in dilated cardiomyopathy: specific findings and long-term prognostic significance.

OBJECTIVE: The objective was to provide an exhaustive characterization of ECG features in a large cohort of dilated cardiomyopathies (DCMs) and then investigate their possible prognostic role in the long term. BACKGROUND: ECG is an accessible, reproducible, low-cost diagnostic and prognostic tool. However, an extensive description of ECG features and their long-term prognostic role in a large cohort of DCM is lacking. METHODS: All available baseline ECGs of DCM patients enrolled from 1992 to 2013 were systematically analysed. Patients underwent to a complete clinical-laboratory evaluation. The study outcome measures were death or heart transplant (D/HT) and sudden death or malignant ventricular arrhythmias (SD/MVA). RESULTS: Four hundred and fourteen DCM patients were enrolled. During a median follow-up of 125 months, 55 and 57 patients experienced D/HT and SD/MVA, respectively. At multivariate analysis, left ventricular hypertrophy (P = 0.017), heart rate (HR, P = 0.005) and anterolateral T-wave inversion (P = 0.041) predicted D/HT. Regarding SD/MVA, S wave amplitude in V2 (P = 0.008), R wave amplitude in DIII (P = 0.007), anterolateral T-wave inversion (P = 0.017) emerged as predictors. At receiver-operating curve analyses, the addition of ECG models to the clinical-laboratory evaluation significantly increased the area under the curve both for D/HT (from 0.68 to 0.74, P = 0.042) and SD/MVA (from 0.70 to 0.77, P = 0.048). CONCLUSION: The exhaustive systematic evaluation of ECG has an incremental impact in the prognostication of a large cohort of DCM patients, also regarding the arrhythmic stratification.

Decompensated congestive heart failure - treatment with levosimendan

The Guidelines Project, an initiative of the Brazilian Medical Association, aims to combine information from the medical field in order to standardize producers to assist the reasoning and decision-making of doctors. The information provided through this project must be assessed and criticized by the physician responsible for the conduct that will be adopted, depending on the conditions and the clinical status of each patient.

Improvement of the outcome in patients with infantile dilated cardiomyopathy over three decades - The usefulness of long-term gradually medical supportive care.

BACKGROUND: The treatment of heart failure has changed with the use of angiotensin-converting enzyme inhibitors (ACEIs) and beta-blockers since the middle of the 1990s. However, the outcome in infantile dilated cardiomyopathy (DCM) when treated with them remains poorly understood. METHODS: We reviewed the medical records of infants with DCM within 24 months old in our hospital between 1979 and 2012, and compared the outcome in the later group (1997-2012) with that in the early group (1979-1996). The survival and cardiac event (CE)-free survival rates were calculated by the Kaplan-Meier method. RESULTS: There were 20 patients in the early group and 24 patients in the later group. The median left ventricular fractional shortening at the onset of disease in the early and later groups were 11% (range 4-17%) and 12% (range 4-25%), respectively. In the later group, ACEIs and beta-blockers were administered in 22 and 21 patients, respectively. An usual low-dose induction of carvedilol therapy (0.01-0.02mg/kg/day) sometimes worsened the heart failure in 9 patients (43%) after the successful initial conventional treatment for acute heart failure. Nineteen patients died and 25 survived. The CEs were as follows: heart transplantation 4, mitral valvuloplasty 1, Batista operation with mitral valve replacement 1, and cardiac resynchronization therapy in the late period 1. The 20-year survival rate in the early and later groups were 5% (95% CI 0.7-28) and 100%, respectively (p<0.001). The 2-year CE-free survival rate in the early and later groups were 5% (95% CI 0.7-28) and 83% (95% CI 59-91), respectively (p<0.001). CONCLUSIONS: The outcome in patients with infantile DCM has significantly improved with careful acute and chronic treatments using ACEIs and beta-blockers since the 2000s. Adopting a long-term supportive treatment during a period of low ventricular function and the use of beta-blockers corresponding to each patient's condition were key to survival.

Arrhythmic risk stratification in patients with dilated cardiomyopathy and intermediate left ventricular dysfunction.

AIMS: Arrhythmic risk stratification is a challenging issue in patients with dilated cardiomyopathy (DCM), particularly when left ventricular ejection fraction (LVEF) is more than 35%. We studied the prevalence and predictors of sudden cardiac death or malignant ventricular arrhythmias (SCD/MVAs) in DCM patients categorized at low arrhythmic risk because of intermediate left ventricular dysfunction under optimal medical treatment (OMT). METHODS: DCM patients considered at low arrhythmic risk (LVEF >35% and New York Heart Association class I-III after 6 ±â€Š3 months of OMT) were analysed. An arrhythmogenic profile was defined as the presence of at least one among a history of syncope, nonsustained ventricular tachycardia, at least 1000 premature ventricular contractions/24 h, at least 50 ventricular couplets/24 h at Holter ECG monitoring. SCD/MVAs was considered as the study end-point. RESULTS: During a median follow-up of 152 months (interquartile range 100-234), 30 out of 360 (8.3%) patients at low arrhythmic risk (LVEF 47 ±â€Š7%) experienced the study end-point [14 (3.9%) SCD and 16 (4.4%) MVA]. Compared with survivors, patients who experienced SCD/MVAs had more frequently an arrhythmogenic profile and a larger left atrium. Their LVEF at the last available evaluation before the arrhythmic event was 36 ±â€Š12%. At multivariable analysis, left atrial end-systolic area [hazard ratio 1.107; 95% confidence interval (95% CI) 1.039-1.179, P = 0.002 for 1 mm increase] and arrhythmogenic profile (hazard ratio 3.667; 95% CI 1.762-7.632, P = 0.001) emerged as predictors of SCD/MVAs during follow-up. CONCLUSION: A consistent quota of DCM patients with intermediate left ventricular dysfunction receiving OMT experienced SCD/MVA during follow-up. Left atrial dilatation and arrhythmogenic pattern were associated with a higher risk of SCD/MVA.

Dilated cardiomyopathy in 151 Irish Wolfhounds: Characteristic clinical findings, life expectancy and causes of death.

Dilated cardiomyopathy (DCM) is an important cause of morbidity in Irish Wolfhounds (IW), a breed also predisposed to neoplastic and orthopedic diseases that shorten life expectancy. The objective of this study was to investigate survival and causes of death in IW with DCM and to characterise the clinical findings of DCM over time. Data from cardiovascular examinations performed in 1591 IW, including echocardiography and electrocardiography, were retrospectively evaluated. IW with DCM on medical therapy with long term longitudinal follow-up were included in this study (n=151; 95 males, 56 females). Based on their clinical status at initial diagnosis, IW were classified into one of three groups: preclinical DCM with sinus rhythm (PC-DCM-SR, n=35), preclinical DCM with atrial fibrillation (PC-DCM-AF, n=87), and congestive heart failure with DCM and AF (CHF-DCM-AF, n=29). Survival data were analyzed using cumulative incidence functions, Kaplan-Meier and Cox regression. CHF was predominantly characterized by chylous pleural and mild pericardial effusions. Causes of death were cardiac (CD) in 73/151 and non-cardiac (non-CD) in 62/151; 16 dogs remained alive at study end. The majority of deaths in both preclinical DCM groups were non-CD (PC-DCM-AF=51.9% non-CD, 48.1% CD; PC-DCM-SR, 65.5% non-CD, 34.5% CD). In the CHF-DCM-AF group most dogs (89.6%) experienced a CD. Median survival of the CHF-DCM-AF group (7.3 months) was significantly shorter than in the PC-DCM-AF group (21.9 months) or PC-DCM-SR group (29.1 months, P=0.001). CHF-DCM-AF in IW was associated with reduced life expectancy and CD, while most IW with preclinical DCM died from non-cardiac causes.

Outcomes of heart transplantation in patients with human immunodeficiency virus.

Human immunodeficiency virus-positive (HIV+) patients are not routinely offered heart transplantation (HT) due to lack of adequate outcomes data. Between January 2004 and March 2017, we identified 41 adult (≥18 years) HT recipients with known HIV+ serostatus at the time of transplant in UNOS and evaluated post-HT outcomes. Overall, Kaplan-Meier (KM) estimates of survival at 1 and 5 years were 85.9% and 77.3%, respectively, with no significant difference in bridge-to-transplant ventricular-assist device (BTT-VAD, n = 22) and no-BTT-VAD (n = 19). KM estimates of cardiac allograft vasculopathy (CAV) and malignancy at 5 years were 32% and 19%, respectively. Using propensity scores, 41 HIV+ HT recipients were matched to 41 HIV- HT recipients for idiopathic dilated-cardiomyopathy; and there was no significant difference in post-HT survival up to 5 years. Furthermore, only 24 centers in the United States had performed HIV+ HT during the study period, indicating that >80% of HT centers in the United States had not performed any HIV+ HT. In a cohort representative of the current status of HIV+ HTs in the United States, we found that the posttransplant survival was excellent and rates of CAV and malignancy were comparable to the overall HT population. These results should encourage greater number of centers to offer HT to suitable HIV+ candidates and help reduce unequal access to HT for HIV+ patients.