Impaired mitochondrial biogenesis is a common feature to myocardial hypertrophy and end-stage ischemic heart failure

Mitochondrial (mt) DNA depletion and oxidative mtDNA damage have been implicated in the process of pathological cardiac remodeling. Whether these features are present in the early phase of maladaptive cardiac remodeling, that is, during compensated cardiac hypertrophy, is still unknown. We compared the morphologic and molecular features of mt biogenesis and markers of oxidative stress in human heart from adult subjects with compensated hypertrophic cardiomyopathy and heart failure. We have shown that mtDNA depletion is a constant feature of both conditions. A quantitative loss of mtDNA content was associated with significant down-regulation of selected modulators of mt biogenesis and decreased expression of proteins involved in mtDNA maintenance. Interestingly, mtDNA depletion characterized also the end-stage phase of cardiomyopathies due to a primary mtDNA defect. Oxidative stress damage was detected only in failing myocardium

Novel compound mutations in the mitochondrial translation elongation factor (TSFM) gene cause severe cardiomyopathy with myocardial fibro-adipose replacement

Primary mitochondrial dysfunction is an under-appreciated cause of cardiomyopathy, especially when cardiac symptoms are the unique or prevalent manifestation of disease. Here, we report an unusual presentation of mitochondrial cardiomyopathy, with dilated phenotype and pathologic evidence of biventricular fibro-adipose replacement, in a 33-year old woman who underwent cardiac transplant. Whole exome sequencing revealed two novel compound heterozygous variants in the TSFM gene, coding for the mitochondrial translation elongation factor EF-Ts. This protein participates in the elongation step of mitochondrial translation by binding and stabilizing the translation elongation factor Tu (EF-Tu). Bioinformatics analysis predicted a destabilization of the EF-Ts variants complex with EF-Tu, in agreement with the dramatic steady-state level reduction of both proteins in the clinically affected myocardium, which demonstrated a combined respiratory chain enzyme deficiency. In patient fibroblasts, the decrease of EF-Ts was paralleled by up-regulation of EF-Tu and induction of genes involved in mitochondrial biogenesis, along with increased expression of respiratory chain subunits and normal oxygen consumption rate. Our report extends the current picture of morphologic phenotypes associated with mitochondrial cardiomyopathies and confirms the heart as a main target of TSFM dysfunction. The compensatory response detected in patient fibroblasts might explain the tissue-specific expression of TSFM-associated disease

Use of Mechanical Circulatory Support Devices in End-Stage Heart Failure Patients

BACKGROUND: Mechanical circulatory support (MCS) is the standard therapy for the management of acute or chronic end-stage heart failure. We report on our two-center experience with MCS therapy. METHODS: Between January 2000 and December 2012, 116 adult patients (mean age 56.8 ± 9.9 years, range: 31 to 76 years) were primarily supported on temporary or long-term ventricular assist devices (VADs) or total artificial hearts (TAHs) at our institutions. Temporary extracorporeal radial VAD support was established in 50 patients (43.1%) (Group A) whereas 66 (56.8%) patients received long-term paracorporeal and intracorporeal VAD or TAH (Group B). LVAD support was established in 63 patients (54.3%), with BVAD/TAH support in 29 (25%). A temporary CentriMag was the only device adopted as an isolated RVAD support, being placed in 24 patients (20.6%). RESULTS: In Group A, the overall mean support time was 10.2 ± 6.6 days (range: 3 to 43 days) and the overall success rate was 55.1% (27 patients). The mean LVAD support time was 357 ± 352.3 days (range: 1 to 902 days) in Group B and 98 ± 82.6 days (range: 8 to 832 days) in BVAD/TAH patients, with success rates of 72.5% (37 patients) and 46.6% (seven patients), respectively. The heart transplantation (Htx) rate for both groups combined was 25.8% (n = 30). The overall one- and five-year survival rates after Htx were 73.3% and 60%, respectively. CONCLUSIONS: When a decision to treat with VAD or TAH is made early, either modality can be used as an alternative to Htx, affording comparable early to mid-term outcomes

ASAIO 2017 DEF.pptx

Presentation given at the ASAIO 2017 Meeting on ALMA score coming out from a multiistitutional experience of LVAD and BiVAD.<div>The factors entering in the ALMA score are analysed regarding their potential reversal before implantation.</div

Primary Cardiac Kaposiform Hemangioendothelioma: The Rare Adult-Onset. Review of the Literature

Hemangioendothelioma (HE) is the term used to name vascular neoplasms that show a borderline biological behaviour, intermediate between entirely benign hemangiomas and highly malignant angiosarcomas. The HE are classified in several types (papillary intralymphatic, kaposiform, epithelioid, retiform, pseudomyogenic and composite). Each of them have characteristic histo-pathological features and in the most of cases they present in childhood. The current scientific literature about HE is limited: infant and child case reports but lack of adult cases. In particularly no reported primary cardiac kaposiform HE has been described in the adult within nowadays. We analyzed all scientific literature and reported an outstanding and extremely rare case of primary cardiac kaposiform HE in the adult and make a comprehensive analysis of the scientific literature of this unusual interesting but not enough known issue

Optimizing the Safety Profile of Everolimus by Delayed Initiation in De Novo Heart Transplant Recipients: Results of the Prospective Randomized Study EVERHEART

Background Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization.Methods This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate 30/mL/min per 1.73 m(2)) in de novo HTx recipients receiving immediate everolimus (EVR-I) (144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint.Results Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02).Conclusions Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy

Extracorporeal Membrane Oxygenation Support in Refractory Cardiogenic Shock: Treatment Strategies and Analysis of Risk Factors

Two centrifugal pumps, the RotaFlow (Maquet, Jostra Medizintechnik AG, Hirrlingen, Germany) and Levitronix CentriMag (Levitronix LCC, Waltham, MA, USA), used in central or peripheral veno-arterial extracorporeal membrane oxygenation (ECMO) support systems have been investigated, in terms of double-center experience, as treatment for patients with refractory cardiogenic shock (CS). Between January 2006 and December 2012, 228 consecutive adult patients were supported on RotaFlow (n=213) or CentriMag (n=15) ECMO, at our institutions (155 men; age 58.3±10.5 years, range: 19-84 years). Indications for support were: failure to wean from cardiopulmonary bypass in the setting of postcardiotomy (n=118) and primary donor graft failure (n=37); postacute myocardial infarction CS (n=27); acute myocarditis (n=6); and CS on chronic heart failure (n=40). A peripheral ECMO setting was established in 126 (55.2%) patients while it was established centrally in 102 (44.7%). Overall mean support time was 10.9±9.7 days (range: 1-43 days). Eighty-four (36.8%) patients died on ECMO. Overall success rate, in terms of survival on ECMO (n=144), weaning from mechanical support (n=107; 46.9%), bridge to mid-long-term ventricular assist device (n=6; 2.6%), and bridge to heart transplantation (n=31; 13.5%), was 63.1%. One hundred twenty-two (53.5%) patients were successfully discharged. Stepwise logistic regression identified blood lactate level and MB isoenzyme of creatine kinase (CK-MB) relative index at 72 h after ECMO initiation, and number of packed red blood cells (PRBCs) transfused on ECMO as significant predictors of mortality on ECMO (P=0.010, odds ratio [OR]=2.94; 95% confidence interval [CI]=1.10-3.14; P=0.010, OR=2.82, 95% CI=1.014-3.721; and P=0.011, OR=2.69; 95% CI=1.06-4.16, respectively). Central ECMO population had significantly higher rate of continuous veno-venous hemofiltration need and bleeding requiring surgery events compared with the peripheral ECMO setting population. No significant differences were seen by comparing the RotaFlow and CentriMag populations in terms of device performance. At follow-up, persistent heart failure with left ventricle ejection fraction (LVEF)≤40% was a risk factor after hospital discharge. Patients with a poor hemodynamic status may benefit from rapid central or peripheral insertion of ECMO. The blood lactate level, CK-MB relative index, and PRBCs transfused should be strictly monitored during ECMO support. In addition, early ventricular assist device placement or urgent listing for heart transplant should be considered in patients with persistent impaired LVEF after ECMO