Advanced Dilated Cardiomyopathy Research Articles

Non-heart transplant surgical approaches with mitral valve operation and surgical ventricular reconstruction for non-ischaemic dilated cardiomyopathy: a Japanese multicenter study.

There is uncertainty over the efficacy of additional surgical ventricular reconstruction (SVR) associated with mitral valve operation for non-ischaemic dilated cardiomyopathy (DCM). This study aims to assess mid-term outcomes of these non-heart transplant surgical approaches for DCM. We reviewed retrospectively 106 patients (median age 64, 44 females) who underwent isolated mitral annular plasty (MAP; n = 34), mitral valve replacement (MVR; n = 29), and SVR associated with MAP (SVR + MAP; n = 43) for DCM, in 11 Japanese hospitals. We analysed mid-term outcomes, specifically freedom from cardiac death and cardiac event. Hospital deaths occurred in 16 patients (15.1%) and cardiac deaths in 36 patients (34.0%) during the study period of 4.4 ± 3.5years. Freedom from cardiac death at 7years in patients undergoing MAP, MVR, and SVR + MAP were, respectively, 79.1%, 82.6%, and 29.5% (P < 0.0001). Freedom from cardiac event at 7years in patients undergoing MAP, MVR, and SVR + MAP were, respectively, 42.8%, 59.9%, 22.6% (P = 0.0004). In the multivariable analyses, preoperative tricuspid regurgitation (TR) grade was the only risk factor for both cardiac death and event, whereas MVR for DCM emerged as a protective factor for cardiac event. This study could not show any benefit of additional SVR, by means of volume reduction, to MAP, because the baseline characteristics were different even after the stratification of DCM grade. MVR can be performed with favorable mid-term outcomes even in patients with advanced DCM, while patients undergoing MAP with/without SVR had more frequent MR recurrence or cardiac events. Interestingly, the right ventricular feature is a predictor of both cardiac death and events, with the TR grade being a predictor of poor mid-term outcomes.

P595Characteristics of the right ventricle in patients with nonischemic dilated cardiomyopathy

Abstract Background In nonischemic dilated cardiomyopathy (DCM), diagnosis and prognosis is based on left ventricular function. Although concomitant right ventricular (RV) dysfunction is frequently observed, the underlying mechanism is currently not fully understood. Purpose We aimed to describe the characteristics of right ventricular function in DCM patients with cardiac magnetic resonance (CMR) imaging using cine and late-gadolinium enhancement (LGE) imaging. Methods Patients with DCM and left ventricular (LV) dysfunction (ejection fraction (EF) &lt;50%) on LGE-CMR were included prospectively. LV and RV volumes and function were quantified and RV systolic dysfunction was defined as RV ejection fraction (RVEF)&lt;45%. The presence and pattern of LGE were assessed visually and the extent was quantified using the full-width half maximum method. Septal midmyocardial LGE pattern was defined as midwall striae or hinge-point myocardial hyperenhancement. Moreover, left atrial (LA) volumes were calculated using the bi-plane area-length method. Results The study included 214 DCM patients (42% female, age 58±14 years) with a mean LVEF of 34±12% and RVEF of 46±12%. RV systolic dysfunction was present in 39% and was associated with the presence of septal midwall LGE (OR 1.96 (95% CI 1.09–3.54) p=0.026). In patients with RV dysfunction, LV dilation was more severe (LV end diastolic volume (EDV) 242±97mL vs. 212±58mL, p=0.011) and LVEF was lowere (26±12% vs. 39±8%, p&lt;0.001) (figure A). There was a weak correlation between septal LGE amount and LVEDV and RVEDV (respectively r=0.36, p=0.003 and r=0.35, p=0.005) In patients with RV dysfunction, left atrial volumes were enlarged (56±23mL/m2 vs. 46±14mL/m2, p&lt;0.001) and LA emptying fraction was moderately correlated to RVEF (figure B), also after exclusion of patients with a history of atrial fibrillation. RVEF in DCM patients Conclusion In DCM, reduced RVEF predominantly occurred in patients with a) LVEF lower than 30%, b) septal midwall enhancement, indicating progressive LV remodeling, c) LA dilation and d) LA dysfunction. This suggests that RV dysfunction in advanced DCM is drive by LV diastolic dysfunction resulting in increased afterload of the RV.

Metabolic Profiling Associates with Disease Severity in Nonischemic Dilated Cardiomyopathy

BackgroundMetabolomic profiling may have diagnostic and prognostic value in heart failure. This study investigated whether targeted blood and urine metabolomics reflects disease severity in patients with nonischemic dilated cardiomyopathy (DCM) and compared its incremental value on top of N-terminal prohormone of brain natriuretic peptide (NT-proBNP). Methods and ResultsA total of 149 metabolites were measured in plasma and urine samples of 273 patients with DCM and with varying stages of disease (patients with DCM and normal left ventricular reverse remodeling, n = 70; asymptomatic DCM, n = 72; and symptomatic DCM, n = 131). Acylcarnitines, sialic acid and glutamic acid are the most distinctive metabolites associated with disease severity, as repeatedly revealed by unibiomarker linear regression, sparse partial least squares discriminant analysis, random forest, and conditional random forest analyses. However, the absolute difference in the metabolic profile among groups was marginal. A decision-tree model based on the top metabolites did not surpass NT-proBNP in classifying stages. However, a combination of NT-proBNP and the top metabolites improved the decision tree to distinguish patients with DCM and left ventricular reverse remodeling from symptomatic DCM (area under the curve 0.813 ± 0.138 vs 0.739 ± 0.114; P = 0.02). ConclusionFunctional cardiac recovery is reflected in metabolomics. These alterations reveal potential alternative treatment targets in advanced symptomatic DCM. The metabolic profile can complement NT-proBNP in determining disease severity in nonischemic DCM.

Acute circulatory failure in two cardiology departments in Dakar: 44 cases.

Acute circulatory failure is a life-threatening emergency whose prognosis depends on early management and aetiological diagnosis. The aim of our study was to assess the epidemiological, aetiological, therapeutic and prognostic aspects of acute circulatory failure in two cardiology departments in Dakar. This was a longitudinal, multicentre, descriptive study over a period of six months from October 2014 to March 2015. We included all patients with acute circulatory failure (systolic blood pressure < 90 mmHg, oligoanuria, tachycardia, tachypnoea, onset of altered consciousness) either on admission or during hospitalisation during the study period. A long-term survival survey (six months to one year) was conducted on all included patients. Forty-four patients were enrolled. The average age was 54.9 years, ranging from 20 to 83 years. The gender ratio was 1.1. Acute circulatory failure occurred most often during hospitalisation (63%), with known cardiomyopathy in 47.7% of cases. Consciousness was impaired in 11 patients while oligoanuria was present in 27.3% of cases. Inflammatory syndrome was mostly found in 63.6% of cases and renal insufficiency and acute liver failure were reported in 45.5 and 29.5% of patients, respectively. Left ventricular dysfunction was the most common echocardiographic feature (70%). Acute circulatory failure was cardiogenic in most cases, with a predominance of advanced dilated cardiomyopathy (44.9%). Septic shock was found in 25% of patients, with pulmonary infection as the main location (20%). Nine per cent of patients had hypovolaemic shock. The most used inotropic drug was dobutamine in 79.5% of cases, followed by adrenaline (18.2%) and norepinephrine (4.5%). Intra-hospital mortality rate was high (52.3%) and one-year survival rate was 27.2%. Poor prognostic factors such as advanced age and renal impairment were associated with a higher overall mortality rate of 18 to 90%, with no statistical significance. Acute circulatory failure is a diagnostic and therapeutic emergency with a high mortality rate.

Novel Genetic Variants in BAG3 and TNNT2 in a Swedish Family with a History of Dilated Cardiomyopathy and Sudden Cardiac Death

Familial dilated cardiomyopathy is a rare cause of dilated cardiomyopathy (DCM), especially in childhood. Our aim was to describe the clinical course and the genetic variants in a family where the proband was a four-month-old infant presenting with respiratory problems due to DCM. In the family, there was a strong family history of DCM and sudden cardiac death in four generations. DNA was analyzed initially from the deceased girl using next-generation sequencing including 50 genes involved in cardiomyopathy. A cascade family screening was performed in the family after identification of the TNNT2 and the BAG3 variants in the proband. The first-degree relatives underwent clinical examination including biochemistry panel, cardiac ultrasound, Holter ECG, exercise stress test, and targeted genetic testing. The index patient presented with advanced DCM. After a severe clinical course, the baby had external left ventricular assist as a bridge to heart transplantation. 1.5 months after transplantation, the baby suffered sudden cardiac death (SCD) despite maximal treatment in the pediatric intensive care unit. The patient was shown to carry two heterozygous genetic variants in the TNNT2 gene [TNNT2 c.518G>A(p.Arg173Gln)] and BAG3 [BAG3 c.785C>T(p.Ala262Val)]. Two of the screened individuals (two females) appeared to carry both the familial variants. All the individuals carrying the TNNT2 variant presented with DCM, the two adult patients had mild or moderate symptoms of heart failure and reported palpitations but no syncope or presyncopal attacks prior to the genetic diagnosis. The female carriers of TNNT2 and BAG3 variants had more advanced DCM. In the family history, there were three additional cases of SCD due to DCM, diagnosed by autopsy, but no genetic analysis was possible in these cases. Our findings suggest that the variants in TNNT2 and BAG3 are associated with a high propensity to life-threatening cardiomyopathy presenting from childhood and young adulthood.

Imaging and 1-day kinetics of intracoronary stem cell transplantation in patients with idiopathic dilated cardiomyopathy

BackgroundStem cell transplantation is an emerging method of treatment for patients with cardiovascular disease. There are few studies completed or ongoing on stem cell therapy in patients with idiopathic dilated cardiomyopathy (IDCM). Information on stem cell homing and distribution in the myocardium after transplantation might provide important insight into effectiveness of transplantation procedure. AimTo assess early engraftment, retention and migration of intracoronarily transplanted stem cells in the myocardium of patients with advanced dilated cardiomyopathy of non-ischaemic origin using stem cell labeling with 99mTc-exametazime (HMPAO). Materials, methodsThirty-five patients with IDCM and advanced heart failure were included in the study. Autologous hematopoietic (CD34+) stem cells were harvested by peripheral blood apheresis after bone marrow stimulation, labeled with 99mTc-HMPAO, tested for viability and injected into coronary vessel supplying areas of myocardium selected by myocardial perfusion scintigraphy as dysfunctional yet viable. Imaging was performed 1h and 18h after transplantation. ResultsMyocardial stem cell retention ranged from 0 to 1.44% on early and 0–0.97% on delayed imaging. Significant efflux of stem cells occurred from site of delivery in this time period (p<0.001). Stem cell viability was not affected by labeling. ConclusionStem cell labeling with 99mTc-HMPAO is a feasible method for stem cell tracking after transplantation in patients with IDCM.

Adrenergic receptor genotype influences heart failure severity and β-blocker response in children with dilated cardiomyopathy.

Background:Adrenergic receptor (ADR) genotypes are associated with heart failure (HF) and β-blocker response in adults. We assessed the influence of ADR genotypes in children with dilated cardiomyopathy (DCM).Methods:Ninety-one children with advanced DCM and 44 with stable DCM were genotyped for three ADR genotypes associated with HF risk in adults: α2cdel322-325, β1Arg389, and β2Arg16. Data were analyzed by genotype and β-blocker use. Mean age at enrollment was 8.5 y.Results:One-year event-free survival was 51% in advanced and 80% in stable DCM. High-risk genotypes were associated with higher left ventricular (LV) filling pressures, higher systemic and pulmonary vascular resistance, greater decline in LV ejection fraction (P < 0.05), and a higher frequency of mechanical circulatory support while awaiting transplant (P = 0.05). While β-blockers did not reduce HF severity in the overall cohort, in the subset with multiple high-risk genotypes, those receiving β-blockers showed better preservation of cardiac function and hemodynamics compared with those not receiving β-blockers (interaction P < 0.05).Conclusion:Our study identifies genetic risk markers that may help in the identification of patients at risk for developing decompensated HF and who may benefit from early institution of β-blocker therapy before progression to decompensated HF.

Cardiac rehabilitation of a patient with an advanced dilated cardiomyopathy: a case report.

The dilated cardiomyopathy is the common type of cardiomyopathy, and its distinctive characteristic is the systolic dysfunction. Not many reports were issued about the efficacy of cardiac rehabilitation in patients with an advanced dilated cardiomyopathy until yet. A 50-year-old man who was diagnosed with dilated cardiomyopathy with congestive heart failure was admitted to the emergency room after a sudden collapse and a ventricular fibrillation was presented in the actual electrocardiogram. After three months, the patient participated in an 8-week cardiac rehabilitation program with electrocardiogram monitoring for 50 minutes per session at five times per week. The maximal oxygen consumption improved from 13.5 to 19.4 mL/kg/min during this time. At 3.9 metabolic equivalents, the myocardial oxygen demand decreased from 21,710 to 12,669 mmHg.bpm and the Borg's scale of perceived exertion decreased from 15 to 9. The left ventricular ejection fraction improved from 14% to 19%. So in this case report will be presented a patient after a successful cardiac rehabilitation program. Before this the patient suffered from a much more advanced dilated cardiomyopathy and was resuscitated from cardiac arrest.

Baseline QRS width and mitral regurgitation behavior after cardiac resynchronization therapy among patients with dilated cardiomyopathy

Background The effect of cardiac resynchronization therapy (CRT) on functional mitral regurgitation (FMR) is reflected on both clinical and echocardiographic response. We sought to assess the behavior of FMR and the response to CRT implantation in relation to the baseline width of the QRS complex among patients with dilated cardiomyopathy (DCM). Patients and methods This is a prospective observational case-control study, including forty patients with advanced DCM who had left bundle branch block (LBBB), QRS ⩾ 130 ms (group 1) and 10 patients with QRS < 130 ms (group 2) both with echocardiographic evidence of dyssynchrony and subjected to CRT in our center. Results Evidence of response to CRT at 6 months, was observed in 31 patients (77.5%) of group 1 Vs 2 (20%) patients of group 2 (p. 0.001). MR improvement was higher among responders to CRT in 31/33 (93.9%) Vs 2/17 patients (11.7%) of the non responders (p. 0.003). FMR improvement was observed in 31 patients of group 1 (77.5%) Vs 2 patients of group 2 (20%) p. value 0.001. Conclusion Among patients with DCM, the degree of FMR regression after CRT seems to be more clear in patients with a baseline QRS width ⩾130 ms and this seems to be associated with better response of the patients to CRT.

Circulation: Cardiovascular Interventions Editors’ Picks

<i>Circulation: Cardiovascular Interventions</i> Editors’ Picks

Mitral Replacement or Repair for Functional Mitral Regurgitation in Dilated and Ischemic Cardiomyopathy: Is it Really the Same?

This was a study to compare the results of mitral valve (MV) repair and MV replacement for the treatment of functional mitral regurgitation (MR) in advanced dilated and ischemic cardiomyopathy (DCM). One-hundred and thirty-two patients with severe functional MR and systolic dysfunction (mean ejection fraction 0.32 ± 0.078) underwent mitral surgery in the same time frame. The decision to replace rather than repair the MV was taken when 1 or more echocardiographic predictors of repair failure were identified at the preoperative echocardiogram. Eighty-five patients (64.4%) received MV repair and 47 patients (35.6%) received MV replacement. Preoperative characteristics were comparable between the 2 groups. Only ejection fraction was significantly lower in the MV repair group (0.308 ± 0.077 vs 0.336 ± 0.076, p = 0.04). Hospital mortality was 2.3% for MV repair and 12.5% for MV replacement (p = 0.03). Actuarial survival at 2.5 years was 92 ± 3.2% for MV repair and 73 ± 7.9% for MV replacement (p = 0.02). At a mean follow-up of 2.3 years (median, 1.6 years), in the MV repair group LVEF significantly increased (from 0.308 ± 0.077 to 0.382 ± 0.095, p < 0.0001) and LV dimensions significantly decreased (p = 0.0001). On the other hand, in the MV replacement group LVEF did not significantly change (from 0.336 ± 0.076 to 0.31 ± 0.11, p = 0.56) and the reduction of LV dimensions was not significant. Mitral valve replacement was identified as the only predictor of hospital (odds ratio, 6; 95% confidence interval, 1.1 to 31; p = 0.03) and overall mortality (hazard ratio, 3.1; 95% confidence interval, 1.1 to 8.9; p = 0.02). In patients with advanced dilated and ischemic cardiomyopathy and severe functional MR, MV replacement is associated with higher in-hospital and late mortality compared with MV repair. Therefore, mitral repair should be preferred whenever possible in this clinical setting.

The extent of early left ventricular reverse remodelling is related to midterm outcomes after restrictive mitral annuloplasty in patients with non-ischaemic dilated cardiomyopathy and functional mitral regurgitation

Restrictive mitral annuloplasty (RMA) can often improve heart failure symptoms and induce left ventricular (LV) reverse remodelling in patients with non-ischaemic dilated cardiomyopathy (DCM) and functional mitral regurgitation. However, it is unknown whether the observed LV reverse remodelling translates into better outcomes or not. Fifty patients with advanced non-ischaemic DCM (age, 64 ± 10 years, 74% men) underwent RMA and were followed up with a mean of 2 years. Preoperatively, all had 3 to 4+ functional mitral regurgitation (MR), an ejection fraction (EF) of 26 ± 8.6 %, an indexed LV end-systolic volume (LVESVI) of 112 ± 47 ml/m(2). All patients received complete semi-rigid undersized ring annuloplasty. Correlations between early reduction in LVESVI at 1 month after the operation and mid-term clinical outcomes were analysed. There was no 30-day mortality. LVESVI significantly decreased to 96 ± 53 ml/m(2) and LVEF improved to 31 ± 15%. During follow-up, 16 (32%) recurred heart failure, of whom 7 (14%) died. The receiver operating characteristic (ROC) curve found that a reduction in LVESVI >8.3% had a sensitivity of 80% and a specificity of 78% in predicting all adverse events. With this cut-off value, there were 30 (60%) responders to reverse remodelling. Responders had significantly better survival (96.4 versus 68.7%, P = 0.007) and freedom from heart failure rate (85.4 versus 31.8%, P = 0.0003) than non-responders at 3 years. In a 1-year follow-up echocardiographic study, non-responders had shown no significant LV reverse remodelling with greater degree of residual MR than responders. The extent of early LV reverse remodelling is related to mid-term mortality, heart failure events and late reverse remodelling and repair durability after RMA for non-ischaemic DCM.

Desmosomal protein gene mutations in patients with idiopathic dilated cardiomyopathy undergoing cardiac transplantation: a clinicopathological study

BackgroudIdiopathic dilated cardiomyopathy (DCM) is the most frequent indication for orthotopic heart transplantation. It has been suggested that mutations in genes encoding desmosomal proteins, more typically associated with arrhythmogenic right...

Exenatide Improves Glucose Homeostasis and Prolongs Survival in a Murine Model of Dilated Cardiomyopathy

BackgroundThere is growing awareness of secondary insulin resistance and alterations in myocardial glucose utilization in congestive heart failure. Whether therapies that directly target these changes would be beneficial is unclear. We previously demonstrated that acute blockade of the insulin responsive facilitative glucose transporter GLUT4 precipitates acute decompensated heart failure in mice with advanced dilated cardiomyopathy. Our current objective was to determine whether pharmacologic enhancement of insulin sensitivity and myocardial glucose uptake preserves cardiac function and survival in the setting of primary heart failure.Methodology/Principal FindingsThe GLP-1 agonist exenatide was administered twice daily to a murine model of dilated cardiomyopathy (TG9) starting at 56 days of life. TG9 mice develop congestive heart failure and secondary insulin resistance in a highly predictable manner with death by 12 weeks of age. Glucose homeostasis was assessed by measuring glucose tolerance at 8 and 10 weeks and tissue 2-deoxyglucose uptake at 75 days. Exenatide treatment improved glucose tolerance, myocardial GLUT4 expression and 2-deoxyglucose uptake, cardiac contractility, and survival over control vehicle-treated TG9 mice. Phosphorylation of AMP kinase and AKT was also increased in exenatide-treated animals. Total myocardial GLUT1 levels were not different between groups. Exenatide also abrogated the detrimental effect of the GLUT4 antagonist ritonavir on survival in TG9 mice.Conclusion/SignificanceIn heart failure secondary insulin resistance is maladaptive and myocardial glucose uptake is suboptimal. An incretin-based therapy, which addresses these changes, appears beneficial.

The GeoForm annuloplasty ring for the surgical treatment of functional mitral regurgitation in advanced dilated cardiomyopathy☆☆☆

To assess the results of the three-dimensional (3D)-shaped GeoForm ring for the treatment of functional mitral regurgitation (FMR). Seventy-four patients with severe FMR and systolic dysfunction underwent GeoForm ring implantation. Forty-six patients (62%) were in the New York Heart Association (NYHA) class III-IV. Concomitant procedures were coronary artery bypass grafting (CABG) (33 patients (pts)), tricuspid repair (23 pts), atrial fibrillation ablation (20 pts), aortic valve replacement (eight pts) and left-ventricular (LV) reconstruction (five pts). Hospital mortality was 9%. Three more patients died after hospital discharge. Overall survival was 81.1 ± 6.6% at 3.5 years. The 67 hospital survivors underwent clinical and echocardiographic follow-up at a mean follow-up period of 1.9 ± 1.25 years (median 1.7 years). MR was absent or mild in 83% of the patients (56/67), moderate in 7% (5/67), and moderate to severe in the remaining 9% (6/67). At 3.5 years, overall freedom from MR ≥ 3+ was 85.1 ± 8% and freedom from MR ≥ 2+ was 75.1 ± 8.6%. Statistical analysis identified preoperative asymmetric tethering with prevalent restricted motion of the posterior leaflet as the only predictor of recurrence of MR ≥ 2+ (hazard ratio (HR) 6.1, p=0.005). Reverse LV remodeling was demonstrated in 31 of the 54 patients eligible for this specific analysis (31/54, 57%): Both LV end-diastolic and end-systolic volumes indexed significantly decreased (both p=0.0001) as well as systolic pulmonary artery pressure (SPAP) (p=0.006). Ejection fraction increased from 33 ± 8% to 43 ± 8% (p<0.0001). Stress echocardiography was performed in a subgroup of eight patients. Mean mitral area at rest was 2.2 ± 0.3 cm² and did not change during stress. Cardiac output significantly increased in all patients during exercise. Although mean and peak transmitral gradients were 3.3 ± 1.3 and 8.1 ± 2.2 mmHg at rest and 6.6 ± 2.5 and 14.8 ± 3.9 mmHg under stress, respectively (both p<0.003), the increase in SPAP was not statistically significant (28 ± 3.0 vs 31 ± 7.5 mm Hg, p=0.17), revealing a preserved cardiac adaptation to exercise. The GeoForm ring is effective in relieving FMR in most of the patients with dilated cardiomyopathy. In presence of prevalent restricted motion of the posterior leaflet, recurrence of significant MR is more likely to occur. Clinically relevant mitral stenosis was not detected during exercise.

The Berlin Heart EXCOR Pediatrics—The SickKids Experience 2004–2008

The ventricular assist device (VAD) Berlin Heart EXCOR Pediatrics was utilized at our institution since 2004 for bridging pediatric patients to cardiac transplantation or myocardial recovery. The present study reviewed our results following VAD implantation. We retrospectively reviewed patients that underwent implantation of a VAD between October 2004 and October 2008. Data collected included age at implantation, gender, weight, underlying disease, pre- and postdevice clinical status, complications, and outcome. Fifteen patients were identified (9 female and 6 male, average age: 8.8 years, range 0.3-14.8; average weight 31.1 kg, range 5.2-86.4). Indications for VAD support were dilated cardiomyopathy in 14 patients and progressing heart failure with a single ventricle physiology (bidirectional Glenn shunt) in one patient. Three patients (20%) were bridged from extracorporeal membrane oxygenation to VAD. Average support was 29 (1-108) days. Fourteen patients were on a bi-VAD, one patient (single ventricle) had single VAD support. Three patients developed mediastinal/pericardial fluid collections, requiring surgical exploration in two, and drain insertion in one. Three patients presented with neurological symptoms. In two patients, a total of three blood pumps were exchanged due to thrombus formation. No patient was weaned off the VAD; two patients (13%) died on the VAD. All surviving patients are neurologically intact at follow-up. In our experience, VAD support provides an effective means of bridging children with advanced dilated cardiomyopathy or heart failure to transplantation with a relatively small number of complications and deaths given the complexity of the patient population.

Not always HIV

A 78-year-old man with a history of hypertension, advanced dilated cardiomyopathy, and longstanding type 2 diabetes mellitus was admitted to hospital because of heart failure. Besides clinical signs of ventricular dysfunction, physical examination showed multiple asymptomatic reddish-purple macular, papular, and nodular skin lesions with surrounding lymphoedema in the man's hands, arms (figure), and legs, which had been present for the past 6 months. Exploration was otherwise unremarkable.

Expression of Extracellular Matrix Genes During Myocardial Recovery From Heart Failure After Left Ventricular Assist Device Support

Abnormalities in the extracellular matrix (ECM) can occur in heart failure. In this study we analyzed ECM gene expression in patients with advanced dilated cardiomyopathy who did and did not develop sustained myocardial recovery after left ventricular assist device (LVAD) unloading combined with pharmacologic therapy. Myocardial gene expression of collagens (COL1A1 and COL3A1), fibronectin (FN), matrix metalloproteinases (MMPs 1 to 14), tissue inhibitors of metalloproteinases (TIMPs 1 to 4), connective tissue growth factor (CTGF), transforming growth factor-beta1 (TGF-beta1) and THY1 was measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) at LVAD implantation and again at explantation (recovery, n = 11) or transplantation (non-recovery, n = 5). The non-recovery group had higher levels of pro-fibrotic markers (COL1A1, TGF-beta1 and THY1) at implantation compared with the recovery group (1.82 +/- 0.74-, 1.81 +/- 0.69- and 3.01 +/- 1.70-fold, respectively; p <or= 0.05). Both recovery and non-recovery groups showed no significant difference in gene expression after treatment, but levels of pro-fibrotic genes (COL1A1, COL3A1, FN and THY1) correlated negatively with post-explant ejection fraction in the recovery group. Of all genes analyzed only TIMP4 showed a significant change, with expression reduced during recovery (0.55 +/- 0.25-fold at explant vs implant, p = 0.001). All other genes showed complex patterns between individuals with both increased and decreased expression of pro-fibrotic markers, MMPs and TIMPs in recovery patients. Patients who did not recover had higher myocardial expression of pro-fibrotic genes at LVAD implantation, and in recovered patients higher levels at explant were negatively associated with subsequent ejection fraction. However, individual patients showed complex expression patterns and a decrease in pro-fibrotic markers was not required for recovery.

Heart Transplantation in a Patient With Systemic Mastocytosis

Systemic mastocytosis is a hematologic disorder characterized by mast-cell proliferation and organ infiltration. A variety of stimuli and drugs can cause severe anaphylaxis in these patients. We report the case of a female patient diagnosed with systemic mastocytosis and advanced dilated cardiomyopathy in whom a heart transplant was successfully performed.

Description of a local cardiac adiponectin system and its deregulation in dilated cardiomyopathy

Despite recent advances in medical therapy, heart failure remains a leading cause for cardiovascular mortality, and its complex pathogenesis is incompletely understood. This study was performed to identify possible new therapeutic targets in dilated cardiomyopathy (DCM). Oligonucleotide microarray analysis was performed on endomyocardial biopsies (EMBs) from patients with early DCM (LVEDD > or = 55 mm, LVEF < or = 55%, n = 5) and control subjects (LVEDD < 55 mm, LVEF > 60%, no cardiac pathology, n = 4). Adiponectin, an adipocytokine involved in cellular metabolism, survival, and immunmodulation, was six-fold downregulated in DCM patients. Microarray data for adiponectin were confirmed by TaqMan-PCR (9.2-fold downregulation, control n= 9 vs. DCM n= 9, respectively, P < 0.05). Immunohistological analysis of EMBs showed significant downregulation of cardiac adiponectin protein expression independent of serum adiponectin (P = 0.36, ns) or serum TNFalpha concentrations (P = 0.46, ns). Neither the adiponectin receptor 1 (adipo-R1) nor adipo-R2 was deregulated in early DCM. Adiponectin mRNA and protein downregulation were confirmed in explanted hearts of patients with advanced DCM (LVEF < 25%, n= 8). In vitro, adiponectin incubation of neonatal rat ventricular myocytes led to activation of the pro-survival kinase PKB/Akt, increased eNOS-phosphorylation, and prevented stress-induced apoptosis of cardiomyocytes in an Akt-dependent manner. Moreover, inhibition of adiponectin secretion was accompanied by an increase in the expression of the cytokine and its receptors. These data indicate the existence of a local cardiac adiponectin system regulated independent of adiponectin and TNFalpha serum levels and its disturbance in cardiac pathology. The study suggests a role for adiponectin in the pathogenesis of DCM and implicates the adipocytokine as a possible future therapeutic target in DCM.