Current state of total artificial heart therapy and introduction of the most important total artificial heart systems.

Due to the declining instances of organ donation, total artificial heart (TAH) therapy is of increasing importance for the management of end-stage biventricular heart failure. We introduce the currently most important established and novel TAH systems (SynCardia, CARMAT, ReinHeart, BiVACOR), report clinical outcomes and discuss technical requirements for the successful implementation of TAH therapy as an alternative to cardiac transplantation.

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Liver failure in total artificial heart therapy.

BACKGROUND: Congestive hepatopathy (CH) and acute liver failure (ALF) are common among biventricular heart failure patients. We sought to evaluate the impact of total artificial heart (TAH) therapy on hepatic function and associated clinical outcomes. METHODS: A total of 31 patients received a Syncardia Total Artificial Heart. Preoperatively 17 patients exhibited normal liver function or mild hepatic derangements that were clinically insignificant and did not qualify as acute or chronic liver failure, 5 patients exhibited ALF and 9 various hepatic derangements owing to CH. Liver associated mortality and postoperative course of liver values were prospectively documented and retrospectively analyzed. RESULTS: Liver associated mortality in normal liver function, ALF and CH cases was 0%, 20% (P=0.03) and 44.4% (P=0.0008) respectively. 1/17 (5.8%) patients with a normal liver function developed an ALF, 4/5 (80%) patients with an ALF experienced a markedly improvement of hepatic function and 6/9 (66.6%) patients with CH a significant deterioration. CONCLUSIONS: TAH therapy results in recovery of hepatic function in ALF cases. Patients with CH prior to surgery form a high risk group with increased liver associated mortality.

A simplified technique for implantation of left ventricular epicardial leads for biventricular re-synchronization using video-assisted thoracoscopy (VATS).

OBJECTIVE: Cardiac re-synchronization therapy for treatment of heart failure requires transvenous insertion of both a right ventricular and left ventricular pacing lead. Implantation of the latter by way of the coronary sinus often fails. Therefore, alternative techniques for insertion are required. We applied a simple video-assisted surgical technique (VATS) using only two ports for the insertion of left-ventricular screw-in electrodes. METHODS: Fifteen patients (M: 10; F: 5; mean age: 62.2 years; range: 46-76 years) with heart failure meeting the ACC/AHA guidelines for implantation of biventricular pacing underwent transvenous insertion of the right atrial sensor lead and the right ventricular pacing lead. In all of them transvenous implantation of the left ventricular pacing lead failed, and they were planned for VATS. In right-lateral decubitus position and under single-lung ventilation a camera port and a flexible instrumentation port were inserted in the forth intercostal space. By using routine instruments, a T-shaped incision was made lateral to the phrenic nerve and an electrode was screwed in. The lead was guided subcutaneously to the pacemaker. RESULTS: Mean skin-to-skin operating time was 55+/-16 min, no conversion to thoracotomy was necessary. All patients were extubated in the operating room and remained in the intensive care unit for less than 24h. Chest tubes were removed after a mean of 1.6+/-0.5 days and the patients were discharged after a mean of 4+/-1.3 days. Intraoperative and postoperative pacing thresholds at 1 and 7 months were satisfactory in all cases and there was no lead dislocation. All but two patients had an improvement of their NYHA function class. There was neither surgical morbidity nor mortality. CONCLUSIONS: Video-assisted thoracoscopy over two ports seems to be an excellent alternative procedure for epicardial lead implantation. It is readily available and produces good pacing results at a short intervention time and tolerable stress for the patients.

Urapidil reduces elevated pulmonary vascular resistance in patients before heart transplantation.

BACKGROUND: Elevated pulmonary vascular resistance is a major limitation for heart transplantation. Urapidil is a centrally and peripherally acting anti-hypertensive drug, able to decrease elevated pulmonary vascular resistance in patients with either chronic obstructive pulmonary disease or heart failure. Urapidil is available as an oral or intravenous drug. In this study, we evaluated the possible beneficial effects of intravenous urapidil in patients with reversible, elevated pulmonary vascular resistance who were scheduled for heart transplantation. METHODS: After approval by the Ethics Committee and written consent, 22 consecutive patients with end-stage heart failure and history of pulmonary vascular resistance >3 Wood units were enrolled into an open, prospective study. Using a (right ventricular ejection fraction) REF-Swan-Ganz catheter, hemodynamics were determined during administration of nitric oxide, and before and after 3 repeated intravenous applications of 10 mg urapidil. The treatment goal was reduction of pulmonary vascular resistance by at least 30%. RESULTS: Twenty-two patients were included to obtain complete data for 14 patients. Eight patients were not treated with urapidil: 7 patients had normal pulmonary vascular resistance at baseline, and 1 patient experienced moderate pulmonary edema before the study began. Two patients did not reach the treatment goal. In patients who responded to urapidil, the following hemodynamic changes were observed: decreased pulmonary vascular resistance (-48%), decreased transpulmonary gradient (20.0 to 13.7 mm Hg), decreased mean pulmonary arterial pressure (40 to 31 mm Hg), decreased systemic vascular resistance (-27%), mean arterial pressure (80 to 72 mm Hg), and increased right heart ejection fraction (21% to 27%). Heart rate remained unchanged. CONCLUSIONS: Intravenous urapidil lowered elevated pulmonary vascular resistance in patients before heart transplantation. In comparison with other vasodilative drugs, the major benefit of urapidil is its oral formulation.

Functional effects of glucose transporters in human ventricular myocardium.

AIMS: Insulin-dependent positive inotropic effects (PIE) are partially Ca(2+) independent. This mechanism is potentially glucose dependent. In contrast to most animal species, human myocardium expresses high levels of sodium-glucose-transporter-1 (SGLT-1) mRNA besides the common glucose-transporters-1 and -4 (GLUT1, GLUT4). METHODS AND RESULTS: We used ventricular myocardium from 61 end-stage failing human hearts (ischaemic cardiomyopathy, ICM and dilated cardiomyopathy, DCM) and 13 non-failing donor hearts. The effect of insulin on isometric twitch force was examined with or without blocking of PI3-kinase, GLUT4-translocation, or SGLT-1. Substrate-dependent (glucose vs. pyruvate vs. palmitoyl-carnitine) effects were tested in atrial myocardium. mRNA expression of glucose transporters was analysed. Insulin increased developed force by 122 + or - 7.4, 121.7 + or - 2.5, and 134.1 + or - 5.7% in non-failing, DCM, and ICM (P < 0.05 vs. DCM), respectively. Positive inotropic effect was partially blunted by inhibition of PI-3-kinase, GLUT4, or SGLT1. Combined inhibition of PI3-kinase and glucose-transport completely abolished PIE. Positive inotropic effect was significantly stronger in glucose-containing solution compared with pyruvate or palmitoyl-carnitine containing. mRNA expression showed only a tendency towards elevated GLUT4-expression in ICM. CONCLUSIONS: Positive inotropic effect of insulin is pronounced in ICM, but underlying mechanisms are unaltered. The Ca(2+)-independent PIE of insulin is mediated via glucose-transporters. Together with the Ca(2+)-dependent PI-3-kinase mediated pathway, it is responsible for the entire PIE. Substrate-dependency affirms a glucose-dependent part of the PIE.

Myeloperoxidase and carbonyl proteins: promising markers for non-invasive monitoring of graft rejection after heart transplantation.

BACKGROUND: After heart transplantation (HTx), endomyocardial biopsy (EMB) is currently the standard method to diagnose acute graft rejection. A non-invasive marker of rejection would be desirable as an alternative or to permit more selective use of the costly and invasive EMB. METHODS: In this retrospective study, outcomes of routinely taken EMBs were used to select 28 patients after HTx EMB Grade 0R (8 patients), 1R (9 patients) or 2R (11 patients). For these patients, myeloperoxidase (MPO) and carbonyl proteins (CP) in serum were measured using enzyme-linked immunoassay (ELISA). RESULTS: MPO and CP levels in post-HTx patients with Grade 2R rejection were significantly (MPO: p < 0.01; CP: p < 0.001) elevated at the time of rejection compared with levels 1 month earlier. MPO and CP levels predicted Grade 2R rejection and the best cut-off point was 237.5 µg/l for MPO and 222.5 pmol/mg for CP, respectively. Clinically most important was the marked increase (doubling of basic values within 1 month) of MPO and CP levels in cases of Grade 2R rejection in post-HTx patients. CONCLUSIONS: MPO and CP seem to be appropriate parameters to monitor rejection events non-invasively and to minimize the application of EMBs after HTx.