Left ventricular assist device implantation after acute anterior wall myocardial infarction and cardiogenic shock: A two-center study

ObjectiveLeft ventricular assist device (LVAD) insertion after anterior wall myocardial infarction complicated by cardiogenic shock is an accepted modality of support in select patients. Results of primary revascularization for these patients are poor. We seek to determine the outcomes of patients with myocardial infarction and shock who undergo LVAD insertion alone versus surgical revascularization before LVAD insertion.MethodsSeventy-four patients at 2 institutions underwent LVAD implantation for myocardial infarction and shock over a 12-year period. Twenty-eight underwent direct LVAD placement, and 46 underwent revascularization through coronary artery bypass grafting before LVAD placement. Variables examined included patient demographics, myocardial infarction–LVAD interval, bridge to transplantation, early mortality (≤30 days), survival after LVAD placement, and posttransplantation survivals.ResultsThere were no differences in demographics between the 2 groups. The group undergoing revascularization before LVAD placement had a lower bridge to transplantation, higher early mortality, and lower overall 6- and 12-month survivals after LVAD placement compared with the group undergoing direct LVAD placement (45.50% vs 70.40%, P = .041; 39.10% vs 14.30%, P = .020; 89.3% and 82.1% vs 54.4% and 52.2%, respectively, P = .006). Posttransplantation survival and LVAD explantation rates were equivalent in both groups.ConclusionsCoronary artery bypass grafting before LVAD insertion for cardiogenic shock complicating myocardial infarction adversely affects survival. Confirmation of these findings would require conducting a large, multicenter, randomized clinical trial comparing revascularization versus LVAD support as primary therapy in this setting

Dysferlin mediates the cytoprotective effects of TRAF2 following myocardial ischemia reperfusion injury

BACKGROUND: We have demonstrated that tumor necrosis factor (TNF) receptor‐associated factor 2 (TRAF2), a scaffolding protein common to TNF receptors 1 and 2, confers cytoprotection in the heart. However, the mechanisms for the cytoprotective effects of TRAF2 are not known. METHODS/RESULTS: Mice with cardiac‐restricted overexpression of low levels of TRAF2 (MHC‐TRAF2(LC)) and a dominant negative TRAF2 (MHC‐TRAF2(DN)) were subjected to ischemia (30‐minute) reperfusion (60‐minute) injury (I/R), using a Langendorff apparatus. MHC‐TRAF2(LC) mice were protected against I/R injury as shown by a significant ≈27% greater left ventricular (LV) developed pressure after I/R, whereas mice with impaired TRAF2 signaling had a significantly ≈38% lower LV developed pressure, a ≈41% greater creatine kinase (CK) release, and ≈52% greater Evans blue dye uptake after I/R, compared to LM. Transcriptional profiling of MHC‐TRAF2(LC) and MHC‐TRAF2(DN) mice identified a calcium‐triggered exocytotic membrane repair protein, dysferlin, as a potential cytoprotective gene responsible for the cytoprotective effects of TRAF2. Mice lacking dysferlin had a significant ≈39% lower LV developed pressure, a ≈20% greater CK release, and ≈29% greater Evans blue dye uptake after I/R, compared to wild‐type mice, thus phenocopying the response to tissue injury in the MHC‐TRAF2(DN) mice. Moreover, breeding MHC‐TRAF2(LC) onto a dysferlin‐null background significantly attenuated the cytoprotective effects of TRAF2 after I/R injury. CONCLUSION: The study shows that dysferlin, a calcium‐triggered exocytotic membrane repair protein, is required for the cytoprotective effects of TRAF2‐mediated signaling after I/R injury

Mechanical Circulatory Support for Right Ventricular Failure

Right ventricular (RV) failure is associated with significant morbidity and mortality, with in-hospital mortality rates estimated as high as 70–75%. RV failure may occur following cardiac surgery in conjunction with left ventricular failure, or may be isolated in certain circumstances, such as inferior MI with RV infarction, pulmonary embolism or following left ventricular assist device placement. Medical management includes volume optimisation and inotropic and vasopressor support, and a subset of patients may benefit from mechanical circulatory support for persistent RV failure. Increasingly, percutaneous and surgical mechanical support devices are being used for RV failure. Devices for isolated RV support include percutaneous options, such as micro-axial flow pumps and extracorporeal centrifugal flow RV assist devices, surgically implanted RV assist devices and veno-arterial extracorporeal membrane oxygenation. In this review, the authors discuss the indications, candidate selection, strategies and outcomes of mechanical circulatory support for RV failure

Functional significance of the discordance between transcriptional profile and left ventricular structure/function during reverse remodeling

To elucidate the mechanisms for reverse LV remodeling, we generated a conditional (doxycycline [dox] off) transgenic mouse tetracycline transactivating factor-TRAF2 (tTA-TRAF2) that develops a dilated heart failure (HF) phenotype upon expression of a proinflammatory transgene, TNF receptor-associated factor 2 (TRAF2), and complete normalization of LV structure and function when the transgene is suppressed. tTA-TRAF2 mice developed a significant increase in LV dimension with decreased contractile function, which was completely normalized in the tTA-TRAF2 mice fed dox for 4 weeks (tTA-TRAF

17β-estradiol effects on human coronaries and grafts employed in myocardial revascularization: a preliminary study

Background: This study was undertaken to compare the in vitro effects of 17β-estradiol on human epicardial coronary arteries, resistance coronary arteries and on arterial vessels usually employed as grafts in surgical myocardial revascularization. Methods: Coronary artery rings (descending coronary artery, right coronary artery, circumflex coronary artery, first septal branch) and arterial graft rings (internal thoracic artery, gastro-epiploic artery) obtained from human heart donors with heart not suitable to cardiac transplantation were connected to force transducer for isometric force recording. Precontracted specimens with and without endothelium were exposed to increasing concentration of 17β-estradiol (3–30–300–3000 nmol/l) and to vehicle (0.1% v/v ethanol). We also evaluated the effects of 17β-estradiol on vessels before and 20 minutes after exposure to L-monomethyl-arginine and indomethacin. Results: 17β-estradiol induced a significant relaxation in all precontracted vessels (mean maximum effect: 78,6% ± 8,5). This effect was not different among the different rings and was not related to the presence of endothelium. N-monomethyl-L-arginine and indomethacin did not modify 17β-estradiol relaxant effect. Conclusion: The vasodilator action of the 17β-estradiol is similar on coronary arteries, resistance coronary arteries and arterial vessels usually employed as grafts in myocardial revascularization

Rad Regulation of CaV12 Channels Controls Cardiac Fight-or-Flight Response

Fight-or-flight responses involve β-adrenergic-induced increases in heart rate and contractile force. In the present study, we uncover the primary mechanism underlying the heart\u27s innate contractile reserve. We show that four protein kinase A (PKA)-phosphorylated residues in Rad, a calcium channel inhibitor, are crucial for controlling basal calcium current and essential for β-adrenergic augmentation of calcium influx in cardiomyocytes. Even with intact PKA signaling to other proteins modulating calcium handling, preventing adrenergic activation of calcium channels in Rad-phosphosite-mutant mice (4SA-Rad) has profound physiological effects: reduced heart rate with increased pauses, reduced basal contractility, near-complete attenuation of β-adrenergic contractile response and diminished exercise capacity. Conversely, expression of mutant calcium-channel β-subunits that cannot bind 4SA-Rad is sufficient to enhance basal calcium influx and contractility to adrenergically augmented levels of wild-type mice, rescuing the failing heart phenotype of 4SA-Rad mice. Hence, disruption of interactions between Rad and calcium channels constitutes the foundation toward next-generation therapeutics specifically enhancing cardiac contractility

Double vs single internal thoracic artery harvesting in diabetic patients: role in perioperative infection rate

Background: The aim of this prospective study is to evaluate the role in the onset of surgical site infections of bilateral internal thoracic arteries harvesting in patients with decompensated preoperative glycemia. Methods: 81 consecutive patients with uncontrolled diabetes mellitus underwent elective CABG harvesting single or double internal thoracic arteries. Single left ITA was harvested in 41 patients (Group 1, 50.6%), BITAs were harvested in 40 (Group 2, 49.4%). The major clinical end points analyzed in this study were infection rate, type of infection, duration of infection, infection relapse rate and total hospital length of stay. Results: Five patients developed sternal SSI in the perioperative period, 2 in group 1 and 3 in group 2 without significant difference. All sternal SSIs were superficial with no sternal dehiscence. The development of infection from the time of surgery took 18.5 ± 2.1 and 7.3 ± 3.0 days for Groups 1 and 2 respectively. The infections were treated with wound irrigation and debridement, and with VAC therapy as well as with antibiotics. The VAC system was removed after a mean of 12.8 ± 5.1 days, when sterilization was achieved. The overall survival estimate at 1 year was 98.7%. Only BMI was a significant predictor of SSI using multivariate stepwise logistic regression analysis (Odds Ratio: 1.34; 95%Conficdence Interval: 1.02–1.83; p value: 0.04). In the model, the use of BITA was not an independent predictor of SSI. Conclusion: CABG with bilateral pedicled ITAs grafting could be performed safely even in diabetics with poor preoperative glycaemic control