Stephane Mahr

Viennese approach to minimize the invasiveness of ventricular assist device implantation

OBJECTIVE Avoiding full sternotomy and cardiopulmonary bypass (CPB) could significantly reduce the invasiveness of left ventricular assist device (LVAD) implantation. Therefore, we developed minimally invasive implant strategies for the Heartware® VAD (HVAD) and the Thoratec® HeartMate II (HMII) covering isolated LVAD implantation as well as concomitant valve procedures (aortic/tricuspid). We present the surgical techniques and the initial clinical experience. METHODS From February 2012 to March 2013, 27 patients (mean age 58 ± 8 years; male 85%; Ischemic Cardiomyopathy 63%; redo surgery 22%; Interagency Registry for Mechanically Assisted Circulatory Support Level I: 29%, II: 22%, III: 33%, IV-VII: 16%) underwent minimally invasive LVAD implantation at our department. Apical cannulation was performed via a left lateral minithoracotomy in HVAD patients (n = 20) or a left subcostal incision in HMII patients (n = 7). The outflow graft anastomosis was performed to the ascending aorta via a right minithoracotomy in the second intercostal space (n = 22) or the right subclavian artery (n = 2). If additional valve procedures (aortic/tricuspid) were necessary (n = 3), a hemisternotomy was performed to access the valve and perform the outflow graft anastomosis. Circulatory support for LVAD implantation was CPB (33%), extracorporeal membrane oxygenation (48%) or off-pump (19%). RESULTS The minimally invasive approach was feasible in all patients with no need for conversions. Thirty-day and in-hospital mortality were 7.4 and 14.8%, respectively. In-hospital stay was 30.0 ± 22.5 days. One patient (4%) died during follow-up from pump thrombus formation. Three patients (11%) underwent surgical revision for bleeding. CONCLUSIONS Minimally invasive LVAD implantation is feasible and safe. The very encouraging results obtained in this initial series justify a broad application of this technique.

Preoperative patient optimization using extracorporeal life support improves outcomes of INTERMACS Level I patients receiving a permanent ventricular assist device.

OBJECTIVES Interagency Registry for Mechanical Assisted Circulatory Support (INTERMACS) Level I patients have the highest early mortality after ventricular assist device (VAD) implantation. This is determined by the exposure of patients in shock with acutely damaged end-organs and high catecholamine support to a significant surgical trauma. We report our experience with a bridge-to-bridge concept consisting of initial veno-arterial extracorporeal life support (ECLS) and deferral of VAD implantation to recovery of end-organ function in INTERMACS Level I patients. METHODS We reviewed the concept of initial ECLS implantation and deferral of VAD implantation to end-organ recovery in 22 consecutive patients (mean age 54 ± 14 years; 72.2% males; 50% ischemic cardiomyopathy; 100% INTERMACS Level I; 18.2% Heartmate II, 68.2% Heartware HVAD, 4.5% Heartware BiVAD, 9.1% DeBakey LVAD) receiving a VAD for refractory cardiogenic shock between June 2004 and February 2013. Study endpoints were end-organ recovery during ECLS and survival. RESULTS ECLS significantly improved renal (creatinine 1.86 ± 0.91 vs 1.32 ± 0.52 mg/dl, P = 0.02), hepatic (aspartate aminotransferase 1426 ± 2176 vs 277 ± 259 U/l, P = 0.04; alanine aminotransferase 982 ± 1466 vs 357 ± 447 U/l, P = 0.04) and pulmonary functions (fraction of inspired oxygen 52 ± 18 vs 26 ± 23%, P < 0.01; positive end-expiratory pressure 7 ± 3 vs 5 ± 4 mbar, P = 0.02) over a period of 8 ± 7 days. Catecholamines could be reduced during ECLS (levosimendan 0.056 ± 0.085 vs 0.010 ± 0.032 μg/kg/min, P = 0.06; dobutamine 4.362 ± 5.268 vs 0.056 ± 0.097 μg/kg/min, P = 0.06; noradrenaline 0.408 ± 0.355 vs 0.056 ± 0.097 μg/kg/min, P < 0.01). Thirty-day and in-hospital mortality after VAD implantation were 4.5 and 9.1%, respectively, and 1-year survival was 86.4%. CONCLUSIONS Preoperative patient optimization using ECLS improves outcomes of INTERMACS Level I patients receiving a permanent VAD.

Effect of cerebral protection strategy on outcome of patients with Stanford type A aortic dissection

OBJECTIVE The aim of the present study was to assess the efficacy and mid- to long-term results of different cerebral protection techniques in the treatment of acute type A aortic dissection. METHODS Between April 1987 and January 2011, 329 patients (220 male patients; median age, 60 years; range, 16-87) with type A aortic dissection underwent replacement of the ascending aorta or aortic arch with an open distal anastomosis. Either hypothermic circulatory arrest alone at 18 °C (n = 116; 35%) or combined with retrograde cerebral perfusion (n = 122; 37%) or antegrade cerebral perfusion at 25 °C (n = 91; 28%) was used. RESULTS The median circulatory arrest time was 30 minutes (range, 12-92). The overall 30-day mortality was 19% (62 of 329). The 30-day mortality stratified by group was 26% (30 patients) in the hypothermic circulatory arrest group, 16% in the retrograde cerebral perfusion group (20 patients), and 13% (12 patients) in the antegrade cerebral perfusion group (P = .047). Permanent neurologic dysfunction occurred in 53 patients (16%), with statistically significant differences among the 3 groups (23% for hypothermic circulatory arrest, 12% for retrograde cerebral perfusion, and 12% for antegrade cerebral perfusion; P = .033). Univariate analysis showed a significant effect of the brain protection strategy on 30-day mortality and neurologic outcome. Multivariate analysis revealed preoperative hemodynamic instability, preoperative resuscitation, age, and operative year as independent predictors of 30-day mortality. Regarding permanent neurologic dysfunction, the multivariate analysis could not identify any independent predictors. Kaplan-Meier analyses revealed statistically significant differences among the 3 groups with a 1-, 3-, and 5-year survival rate of 84%, 79%, and 77% with antegrade cerebral perfusion, 75%, 72%, and 66% with retrograde cerebral perfusion, and 66%, 62%, and 60% with hypothermic circulatory arrest alone. CONCLUSIONS Patients in the antegrade cerebral perfusion group had the best short- and long-term survival rates. However, during the study period, several significant improvements in the treatment of patients with type A aortic dissection were achieved; therefore, independent predictors of mortality and permanent neurologic dysfunction were difficult to identify.

Safety and efficacy of statin therapy in patients switched from cyclosporine a to sirolimus after cardiac transplantation.

Introduction. Statins are an established therapy after cardiac transplantation. Sirolimus (Srl) has been used successfully in cardiac transplant patients. However, potential side effects are hyperlipidemia and interactions with statins. The aim of the study was to evaluate the safety and efficacy of statin therapy after switch to a Srl-based immunosuppression. Patients and Methods. Ninety-eight long-term patients were switched from Cyclosporine A to Srl. Also all patients received mycophenolate mofetil alone or mycophenolate mofetil plus steroid therapy. Reasons for switch were renal dysfunction, graftvasculopathy, or skin cancer. Patients were switched 7.8±4.7 years after transplant. Total observation period was 12 months before and after switch, respectively. Safety evaluation consisted of regular measurements of CPK and liver enzymes to evaluate the incidence myopathy and hepatoxicity. Efficacy analysis was performed by serial blood lipid assessments (low-density lipoprotein, high-density lipoprotein, total cholesterol, and triglycerides). Results. Forty-three percentage of patients received atorvastatin, 38% pravastatin, and 18% other drugs or therapy changes. Most lipid blood levels increased significantly after switch (cholesterol: 192.9±38.6 mg/dL vs. 221.8±49.2 mg/dL, P<0.0001; low-density lipoprotein: 108.0±35.6 mg/dL vs. 123.8±37.9 mg/dL, P<0.0001; and triglycerides: 178.3±88.2 mg/dL vs. 225.5±139.1 mg/dL, P<0.0001). Blood lipid levels after switch were not associated with statin type. Overall safety was acceptable, although incidence of myopathy doubled after switch (n=20 vs. 40; P<0.01). However, most cases were asymptomatic CPK elevations in the pravastatin group. Hepatotoxicity rate was 4% and only temporary. Conclusion. Statin therapy after switch from cyclosporine A to Srl in long-term cardiac transplant patients is safe. However, regular testing of blood lipids and CPK should be mandatory.

Low-molecular-weight heparin for anti-coagulation after left ventricular assist device implantation

BACKGROUND Anti-coagulation is required in patients with left ventricular assist devices (LVADs). We evaluated the feasibility of low-molecular-weight heparin (LMWH) for initiation of anti-coagulation and transitioning to oral anti-coagulation after LVAD implantation. METHODS This single-center study included 78 consecutive patients who underwent either Thoratec HeartMate II LVAD (n = 27) or HeartWare ventricular assist device (HVAD, n = 51) implantation. The LMWHs enoxaparin (n = 50) and dalteparin (n = 28) were used. LMWH was started within 24 hours post-operatively in 79.5% of patients. No anti-coagulation was given before starting LMWH therapy. LMWH activity was monitored by determination of anti-factor Xa levels in plasma. RESULTS The majority of patients (80.7%) had peak anti-Xa activity within the defined range of efficacy of 0.2 to 0.4 IU/ml by the second day of treatment. Mean effective peak anti-Xa activity was 0.28 ± 0.06 IU/ml. Mean duration of anti-coagulation with LMWH was 25.8 ± 18 days. Ischemic strokes were observed in 3 patients (3.8%), with a total of 4 events. Three events occurred while on LMWH, and 1 event occurred during follow-up on oral anti-coagulation. There was 1 fatal stroke. No pump thrombus was observed. Major bleeding was observed in 5 patients (6.4%), with a total of 6 events. Gastrointestinal bleeding was the most common complication (n = 3). There were no fatal bleeding events. CONCLUSIONS LMWH in the setting of LVAD shows rapid and constant biologic efficacy. Anti-coagulation with LMWH appears feasible after LVAD implantation. These findings support further evaluation of LMWH as an alternative to unfractionated heparin in this patient cohort.

Off-Pump HeartWare Ventricular Assist Device Implantation With Outflow Graft Anastomosis to the Left Subclavian Artery

A novel, off-pump implantation technique for the HeartWare ventricular assist device with outflow graft anastomosis to the left subclavican artery is described. Cannulation of the left ventricular apex is performed through an incision in the left fourth or fifth intercostal space. The outflow graft is anastomosed to the left subclavian artery after tunneling through the left thoracic cavity and the first intercostal space. This technique is especially appealing in redo cases as well as in patients with significant calcifications of the ascending aorta or in destination-therapy patients.

Unexpected low incidence of vertebral fractures in heart transplant recipients: analysis of bone turnover.

Heart transplantation (HTX) is associated with a reduction in bone mineral density (BMD). Different markers of bone metabolism have been used, and the applied immunosuppressive regimens have also changed over time. This study was performed to re‐investigate bone metabolism in HTX recipients. Twenty‐five HTX recipients were compared with 25 HTX candidates in respect of biochemical parameters of bone metabolism, BMD, and the frequency of fractures for 1 year. Osteopenia or osteoporosis was observed in approximately two‐thirds of the HTX recipients. Nevertheless, only three (12%) HTX recipients developed a vertebral fracture within 1 year after transplantation; no peripheral fractures occurred. Compared with HTX candidates, HTX recipients had lower serum levels of osteocalcin, and higher serum levels of cross‐linked‐N‐telopeptide of type I collagen (NTX). In HTX recipients, osteocalcin initially reached a nadir, increased during the first 3 months, and decreased thereafter. Bone‐specific alkaline phosphatase initially increased and then decreased. Serum levels of NTX and parathyroid hormone remained high throughout the year. Despite a high bone turnover, an unexpectedly low rate of vertebral fractures was registered. Nevertheless, each fragility fracture is a serious complication and we need to take steps to prevent this complication.

Investigation of hemodynamics in the assisted isolated porcine heart

Background Currently, the interaction between rotary blood pumps (RBP) and the heart is investigated in silico, in vitro, and in animal models. Isolated and defined changes in hemodynamic parameters are unattainable in animal models, while the heart-pump interaction in its whole complexity cannot be modeled in vitro or in silico. Aim The aim of this work was to develop an isolated heart setup to provide a realistic heart-pump interface with the possibility of easily adjusting hemodynamic parameters. Methods A mock circuit mimicking the systemic circulation was developed. Eight porcine hearts were harvested using a protocol similar to heart transplantation. Then, the hearts were resuscitated using Langendorff perfusion with rewarmed, oxygenated blood. An RBP was implanted and the setup was switched to the “working mode” with the left heart and the RBP working as under physiologic conditions. Both the unassisted and assisted hemodynamics were monitored. Results In the unassisted condition, cardiac output was up to 9.5 L/min and dP/dtmax ranged from 521 to 3621 mmHg/s at a preload of 15 mmHg and afterload of 70 mmHg. With the RBP turned on, hemodynamics similar to heart-failure patients were observed in each heart. Mean pump flow and flow pulsatility ranged from 0 to 11 L/min. We were able to reproduce conditions with an open and closed aortic valve as well as suction events. Conclusions An isolated heart setup including an RBP was developed, which combines the advantages of in silico/vitro methods and animal experiments. This tool thus provides further insight into the interaction between the heart and an RBP.

Interaction of a Transapical Miniaturized Ventricular Assist Device With the Left Ventricle: Hemodynamic Evaluation and Visualization in an Isolated Heart Setup.

New left ventricular assist devices (LVADs) offer both important advantages and potential hazards. VAD development requires better and expeditious ways to identify these advantages and hazards. We validated in an isolated working heart the hemodynamic performance of an intraventricular LVAD and investigated how its outflow cannula interacted with the aortic valve. Hearts from six pigs were explanted and connected to an isolated working heart setup. A miniaturized LVAD was implanted within the left ventricle (tMVAD, HeartWare Inc., Miami Lakes, FL, USA). In four experiments blood was used to investigate hemodynamics under various loading conditions. In two experiments crystalloid perfusate was used, allowing visualization of the outflow cannula within the aortic valve. In all hearts the transapical miniaturized ventricular assist device (tMVAD) implantation was successful. In the blood experiments hemodynamics similar to those observed clinically were achieved. Pump speeds ranged from 9 to 22 krpm with a maximum of 7.6 L/min against a pressure difference between ventricle and aorta of ∼50 mm Hg. With crystalloid perfusate, central positioning of the outflow cannula in the aortic root was observed during full and partial support. With decreasing aortic pressures the cannula tended to drift toward the aortic root wall. The tMVAD could unload the ventricle similarly to LVADs under conventional cannulation. Aortic pressure influenced central positioning of the outflow cannula in the aortic root. The isolated heart is a simple, accessible evaluation platform unaffected by complex reactions within a whole, living animal. This platform allowed detection and visualization of potential hazards.

Heart transplantation in Vienna: 25 years of experience

SummarySince the beginning of the University of Vienna Cardiac Transplant Program in 1984, 1113 heart transplant procedures have been performed through August of 2008. One- and five-year survival has increased steadily over time (82% and 76%). Ten-year survival is 65%. Over the past 25 years our program has seen dramatic changes in patient selection, accepting now patients with more risk factors (e.g. age, diabetes, elevated pulmonary resistance). Developments in immunosuppression have decreased incidence of infection, rejection and graftarteriosclerosis continuously. Our program continues to pursue novel strategies to improve the survival and quality of life of our heart transplant patients.