Evgenij V. Potapov

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Long-Term Results in Patients With Idiopathic Dilated Cardiomyopathy After Weaning From Left Ventricular Assist Devices

Background—Since our first successful left ventricular assist device (LVAD) explantation in a patient with idiopathic dilated cardiomyopathy (IDCM) in 1995, an additional 31 IDCM patients have been weaned in our department. Echocardiographic evaluations during repeated “off-pump” trials were the cornerstone for weaning decisions. After 9 years of experience, we assessed the reliability of our weaning criteria in light of the long-term results. Methods and Results—We evaluated all of the IDCM patients who were weaned between March 1995 and March 2004 with regard to preservation of cardiac function without LVAD support and survival after weaning. Additionally, we reviewed our echocardiographic data to assess their predictive value for long-term stability of cardiac function after weaning. The 32 weaned IDCM patients showed a survival rate of 78.3%±8.1 at 5 years after LVAD explantation. Heart failure (HF) recurred during the first 3 years after weaning in 31.3%. Only 2 patients died because of HF after weaning; the other patients with HF recurrence were successfully transplanted. Off-pump LV end-diastolic diameter >55 mm and/or LVEF <45% before LVAD removal, as well as history of HF ≥5 years before LVAD implantation, appeared to be major risk factors for early recurrence of HF. Patients without any of these 3 risk factors showed no HF recurrence during the first 3 years after weaning, but at the same time, all of those with at least 2 of these 3 risk factors developed early recurrence of HF. In patients with HF recurrence during the first 3 postweaning years, a significant LVEF decrease already occurred during the first month after weaning, whereas in those with long-term stable cardiac function even at the end of the sixth postweaning month, the LVEF was not different from that before LVAD removal. Conclusions—For selected patients with IDCM, weaning from LVADs is a clinical option with good results over >9 years and should, therefore, be considered in those with cardiac recovery after LVAD implantation. Off-pump echocardiographic data are reliable for the detection of LV recovery and prediction of long-term cardiac stability after weaning.

Tricuspid Incompetence and Geometry of the Right Ventricle as Predictors of Right Ventricular Function After Implantation of a Left Ventricular Assist Device

BACKGROUND Implantation of a left ventricular assist device (LVAD) is an established treatment for end-stage heart failure. Right ventricular (RV) dysfunction develops in 20% to 50% of patients after LVAD implantation, leading to prolonged ICU stay and elevated mortality. However, the prediction of RV failure remains difficult. METHODS The pre-operative echocardiographic parameters, tricuspid incompetence (TI), RV end-diastolic diameter (cut-off >35 mm), RV ejection fraction (cut-off <30%), right atrial dimension (cut-off >50 mm) and short/long axis ratio (cut-off >0.6), were analyzed retrospectively in 54 patients. Patients were divided into two groups. One group consisted of patients with RV failure (n = 9), as defined by the presence of two of the following criteria in the first 48 hours after surgery: mean arterial pressure < or =55 mm Hg; central venous pressure > or =16 mm Hg; mixed venous saturation < or =55%; cardiac index 20 units; or need for an RVAD. The other patients comprised the non-RV-failure group (n = 45). RESULTS The RV failure group had a significantly higher short/long axis ratio of the RV (0.63 vs 0.52, p = 0.03; odds ratio 4.4, p = 0.011). For patients with a short/long axis ratio of the RV of <0.6, RV failure occurred in 7% of patients, as compared with 50% for patients with a ratio > or =0.6 (p = 0.013). Among patients with TI Grade III or IV, 75% developed RV failure as compared with 12% in patients with TI Grade I or II (p = 0.054). The odds ratio for RV failure after LVAD implantation for TI Grade III or IV was 4.7 (p = 0.012). CONCLUSIONS Pre-operative evaluation of tricuspid incompetence and RV geometry may help to select patients who would benefit from biventricular support.

Tissue-Engineering Bioreactors: A New Combined Cell-Seeding and Perfusion System for Vascular Tissue Engineering

One approach to the tissue engineering of vascular structures is to develop in vitro conditions in order ultimately to fabricate functional vascular tissues before final implantation. In our experiment, we aimed to develop a new combined cell seeding and perfusion system that provides sterile conditions during cell seeding and biomechanical stimuli in order to fabricate autologous human vascular tissue in vitro. The cell seeding and perfusion system is made of Plexiglas and is completely transparent (Berlin Heart, Berlin, Germany; University Hospital Benjamin Franklin, Berlin, Germany). The whole system consists of a cell seeding chamber that can be incorporated into the perfusion system and an air-driven respirator pump connected to the bioreactor. The cell culture medium continuously circulates through a closed-loop system. We thus developed a cell seeding device for static and dynamic seeding of vascular cells onto a polymeric vascular scaffold and a closed-loop perfused bioreactor for long-term vascular conditioning. The cell seeding chamber can be easily connected to the bioreactor, which combines continuous, pulsatile perfusion and mechanical stimulation to the tissue-engineered conduit. Adjusting the stroke volume, the stroke rate, and the inspiration/expiration time of the ventilator allows various pulsatile flows and different levels of pressure. The whole system is a highly isolated cell culture setting, which provides a high level of sterility and a gas supply and fits into a standard humidified incubator. The device can be sterilized by ethylene oxide and assembled with a standard screwdriver. Our newly developed combination of a cell seeding and conditioning device provides sterile conditions and biodynamic stimuli for controlled tissue development and in vitro conditioning of an autologous tissue-engineered vessel.

Prediction of Cardiac Stability After Weaning From Left Ventricular Assist Devices in Patients With Idiopathic Dilated Cardiomyopathy

Background— During ventricular assist device (VAD) unloading, cardiac recovery is possible even in patients with chronic heart failure (HF). We sought parameters predictive of cardiac stability after VAD removal. Methods and Results— Among 81 patients weaned since March 1995, a homogenous group of 35 with idiopathic dilated cardiomyopathy weaned from left VADs was selected. We evaluated echo data obtained before left VAD implantation and during “off-pump” trials before explantation, histological changes, and serum anti-&bgr;1-adrenoceptor-autoantibody disappearance during unloading, duration of unloading, and HF duration. Postweaning 10-year survival with native hearts reached 70.7±9.2%. During the first 5 years, HF recurred in 13 patients (37.1%). Only 6 (17.1%) died after HF recurrence or noncardiac complications related to left VAD explantation. Comparison of patients with and without long-term cardiac stability showed that stable patients were younger, HF history and recovery time during unloading shorter, and preweaning left ventricular assessment revealed higher left ventricular ejection fraction, lower short/long axis ratios, and higher end diastolic relative wall thicknesses. For left ventricular ejection fraction ≥45% at end diastolic diameter of ≤55 mm, predictive value for ≥5-year cardiac stability was 87.5%. Left ventricular ejection fraction time course during the first 6 postweaning months appeared predictive for long-term stability. HF history >5 years and preweaning instability of cardiac improvement appeared predictive for HF recurrence. Conclusions— In idiopathic dilated cardiomyopathy, left VAD removal can be successful for >12 years even with incomplete cardiac recovery. Pre-explantation left ventricular ejection fraction, left ventricular end diastolic diameter and relative wall thicknesses, stability of unloading-induced cardiac recovery, duration of left VAD support, and HF duration before left VAD insertion allow identification of patients able to remain stable for >5 years. Time course of left ventricular ejection fraction during the first 6 postweaning months allows prognostic assessment.

Application of stereolithography for scaffold fabrication for tissue engineered heart valves.

A crucial factor in tissue engineering of heart valves is the functional and physiologic scaffold design. In our current experiment, we describe a new fabrication technique for heart valve scaffolds, derived from x-ray computed tomography data linked to the rapid prototyping technique of stereolithography. To recreate the complex anatomic structure of a human pulmonary and aortic homograft, we have used stereolithographic models derived from x-ray computed tomography and specific software (CP, Aachen, Germany). These stereolithographic models were used to generate biocompatible and biodegradable heart valve scaffolds by a thermal processing technique. The scaffold forming polymer was a thermoplastic elastomer, a poly-4-hydroxybutyrate (P4HB) and a polyhydroxyoctanoate (PHOH) (Tepha, Inc., Cambridge, MA). We fabricated one human aortic root scaffold and one pulmonary heart valve scaffold. Analysis of the heart valve included functional testing in a pulsatile bioreactor under subphysiological and supraphysiological flow and pressure conditions. Using stereolithography, we were able to fabricate plastic models with accurate anatomy of a human valvular homograft. Moreover, we fabricated heart valve scaffolds with a physiologic valve design, which included the sinus of Valsalva, and that resembled our reconstructed aortic root and pulmonary valve. One advantage of P4HB and PHOH was the ability to mold a complete trileaflet heart valve scaffold from a stereolithographic model without the need for suturing. The heart valves were tested in a pulsatile bioreactor, and it was noted that the leaflets opened and closed synchronously under subphysiological and supraphysiological flow conditions. Our preliminary results suggest that the reproduction of complex anatomic structures by rapid prototyping techniques may be useful to fabricate custom made polymeric scaffolds for the tissue engineering of heart valves.

Biventricular Circulatory Support With Two Miniaturized Implantable Assist Devices

Background— Up to 30% of patients with end-stage heart failure experience biventricular failure that requires biventricular mechanical support. For these patients, only bulky extracorporeal or implantable displacement pumps or the total artificial heart have been available to date, which enables only limited quality of life for the patients. It was our goal to evaluate a method that would allow the use of 2 implantable centrifugal left ventricular assist devices as a biventricular assist system. Methods and Results— Seventeen patients have been implanted with 2 HeartWare HVAD pumps, 1 as a left ventricular assist device and 1 as a right ventricular assist device. Seventy-seven percent of the patients had idiopathic dilated or ischemic cardiomyopathy. Their age ranged from 29 to 73 years (mean 51.8±14.5 years), and 11 (64.7%) received intravenous catecholamine support preoperatively. The right ventricular assist device pump was implanted into the right ventricular free wall. The afterload of this pump was artificially increased by local reduction of the outflow graft diameter, and the effective length of its inflow cannula was reduced by the addition of two 5-mm silicon suture rings to the original HVAD implantation ring. All right ventricular assist device devices could be operated in appropriate speed ranges and delivered a flow of between 3.0 and 5.5 L/min. Thirty-day survival was 82%, and 59% of the patients could be discharged home after recovering from the operation. There was no clinically relevant hemolysis in any of the patients. Conclusions— Two HeartWare HVAD pumps can be used as a biventricular assist system. This implantable biventricular support gives the patients more comfort and mobility than usual biventricular ventricular assist devices with large and noisy displacement pumps.

First Experiences With the HeartWare Ventricular Assist System in Children

PURPOSE The purpose of this study is to describe initial experience with a new continuous flow, ventricular assist system in the pediatric population. DESCRIPTION Seven children (aged 6 to 16 years) received implantation of a novel third-generation, continuous flow, ventricular assist device (HeartWare, HeartWare Inc, Miami Lakes, FL) as a bridge to cardiac transplantation. EVALUATION All children were in terminal heart failure despite inotropic support, and signs of renal or hepatic impairment developed. Six children had dilatative cardiomyopathy and 1 had congenital heart disease (hypoplastic left heart, total cavopulmonary connections with extracardiac conduit). Six patients have been successfully bridged to transplantation. Median support time was 75 days (range, 1 to 136 days). One child is still under continuous mechanical support. None of the patients suffered a thromboembolic event or an infection. CONCLUSIONS The HeartWare assist system can be successfully used as a bridge to transplantation in children and adolescents with end-stage heart failure.

Right-to-left ventricular end-diastolic diameter ratio and prediction of right ventricular failure with continuous-flow left ventricular assist devices.

BACKGROUND Left ventricular assist device (LVAD) implantation is an accepted therapy for patients with end-stage heart failure. Post-operative right ventricular failure (RVF) still remains a major cause of morbidity and mortality in these patients. This study sought to identify echocardiography parameters to select patients with high risk of RVF after LVAD implantation. METHODS Prospectively collected pre-operative transesophageal echocardiography (TEE) and clinical data were evaluated in patients pre-selected for isolated LVAD or biventricular assist device (BiVAD) implantation. According to prevalence of RVF during the first post-operative 48 hours, patients were divided into those who developed RVF (isolated LVAD with RVF) and those who did not (isolated LVAD without RVF). Echocardiographic parameters for RV geometry, RV function, LV geometry, and the RV-to-LV end-diastolic diameter ratio (R/L ratio) were evaluated. For identification of the optimal cutoff of R/L ratio, receiver operating characteristics curves were constructed. RESULTS An isolated LVAD was implanted in 115 patients and BiVAD in 22 patients. RVF developed in 15 patients (13%) after isolated LVAD implantation. The R/L ratio was markedly increased in the isolated LVAD with RVF and BiVAD groups compared with the isolated LVAD without RVF group. According to the receiving operating curve, the cutoff for the R/L ratio to predict RVF was 0.72. The odds ratio that RVF will develop is 11.4 in patients with an R/L ratio >0.72 (p = 0.0001). CONCLUSIONS Increased R/L ratio successfully identifies patients with high risk of RVF after isolated LVAD implantation. Beyond standard measurements of RV function, the consideration of R/L ratio may be useful to improve risk stratification in patients before isolated LVAD implantation.

Heart failure reversal by ventricular unloading in patients with chronic cardiomyopathy: criteria for weaning from ventricular assist devices

Aims Unloading-promoted reversal of heart failure (HF) allows long-term transplant-free outcome after ventricular assist device (VAD) removal. However, because few patients with chronic cardiomyopathy (CCM) were weaned from VADs (the majority only recently), the reliability of criteria used for weaning decisions to predict long-term post-weaning success is barely known. After 15 years of weaning experience, we assessed this issue. Methods and results In 47 patients with CCM as the underlying cause for HF, who were part of a total of 90 patients weaned from bridge-to-transplant-designed VADs since 1995, we analysed data on cardiac morphology and function collected before VAD implantation, echocardiographic parameters recorded during ‘off-pump’ trials, duration of HF before implantation, and stability of recovery before and early after VAD removal. Post-weaning 5 year freedom from HF recurrence reached 66%. Only five patients (10.6%) died due to HF recurrence or weaning-related complications. Pre-explantation off-pump left ventricular ejection fraction (LVEF) of ≥50 and ≥45% revealed predictive values for cardiac stability lasting ≥5 years after VAD removal of 91.7 and 79.1%, respectively. With each unit of LVEF reduction, the risk of HF recurrence became 1.5 times higher. The predictive value of LVEF ≥45% also became >90% if additional parameters like pre-explantation LV size and geometry, stability of unloading-induced cardiac improvement before VAD removal, and HF duration before VAD implantation were also considered. Definite cut-off values for certain parameters (including tissue-Doppler-derived LV wall motion velocity) allowed formulation of weaning criteria with high predictability for post-weaning stability, also in patients with incomplete cardiac recovery. Conclusions Ventricular assist device removal in CCM patients is feasible and can be successful even after incomplete cardiac recovery. Parameters of pre-explantation cardiac function, LV size and geometry, their stability during final off-pump trials, and HF duration allow detection of patients with the potential to remain stable for >5 post-weaning years.