Nader Moazami

Extended Mechanical Circulatory Support With a Continuous-Flow Rotary Left Ventricular Assist Device

OBJECTIVES This study sought to evaluate the use of a continuous-flow rotary left ventricular assist device (LVAD) as a bridge to heart transplantation. BACKGROUND LVAD therapy is an established treatment modality for patients with advanced heart failure. Pulsatile LVADs have limitations in design precluding their use for extended support. Continuous-flow rotary LVADs represent an innovative design with potential for small size and greater reliability by simplification of the pumping mechanism. METHODS In a prospective, multicenter study, 281 patients urgently listed (United Network of Organ Sharing status 1A or 1B) for heart transplantation underwent implantation of a continuous-flow LVAD. Survival and transplantation rates were assessed at 18 months. Patients were assessed for adverse events throughout the study and for quality of life, functional status, and organ function for 6 months. RESULTS Of 281 patients, 222 (79%) underwent transplantation, LVAD removal for cardiac recovery, or had ongoing LVAD support at 18-month follow-up. Actuarial survival on support was 72% (95% confidence interval: 65% to 79%) at 18 months. At 6 months, there were significant improvements in functional status and 6-min walk test (from 0% to 83% of patients in New York Heart Association functional class I or II and from 13% to 89% of patients completing a 6-min walk test) and in quality of life (mean values improved 41% with Minnesota Living With Heart Failure and 75% with Kansas City Cardiomyopathy questionnaires). Major adverse events included bleeding, stroke, right heart failure, and percutaneous lead infection. Pump thrombosis occurred in 4 patients. CONCLUSIONS A continuous-flow LVAD provides effective hemodynamic support for at least 18 months in patients awaiting transplantation, with improved functional status and quality of life. (Thoratec HeartMate II Left Ventricular Assist System [LVAS] for Bridge to Cardiac Transplantation; NCT00121472).

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

Right ventricular failure in patients with the HeartMate II continuous-flow left ventricular assist device: incidence, risk factors, and effect on outcomes.

OBJECTIVE The aim of this study was to evaluate the incidence, risk factors, and effect on outcomes of right ventricular failure in a large population of patients implanted with continuous-flow left ventricular assist devices. METHODS Patients (n = 484) enrolled in the HeartMate II left ventricular assist device (Thoratec, Pleasanton, Calif) bridge-to-transplantation clinical trial were examined for the occurrence of right ventricular failure. Right ventricular failure was defined as requiring a right ventricular assist device, 14 or more days of inotropic support after implantation, and/or inotropic support starting more than 14 days after implantation. Demographics, along with clinical, laboratory, and hemodynamic data, were compared between patients with and without right ventricular failure, and risk factors were identified. RESULTS Overall, 30 (6%) patients receiving left ventricular assist devices required a right ventricular assist device, 35 (7%) required extended inotropes, and 33 (7%) required late inotropes. A significantly greater percentage of patients without right ventricular failure survived to transplantation, recovery, or ongoing device support at 180 days compared with patients with right ventricular failure (89% vs 71%, P < .001). Multivariate analysis revealed that a central venous pressure/pulmonary capillary wedge pressure ratio of greater than 0.63 (odds ratio, 2.3; 95% confidence interval, 1.2-4.3; P = .009), need for preoperative ventilator support (odds ratio, 5.5; 95% confidence interval, 2.3-13.2; P < .001), and blood urea nitrogen level of greater than 39 mg/dL (odds ratio, 2.1; 95% confidence interval, 1.1-4.1; P = .02) were independent predictors of right ventricular failure after left ventricular assist device implantation. CONCLUSIONS The incidence of right ventricular failure in patients with a HeartMate II ventricular assist device is comparable or less than that of patients with pulsatile-flow devices. Its occurrence is associated with worse outcomes than seen in patients without right ventricular failure. Patients at risk for right ventricular failure might benefit from preoperative optimization of right heart function or planned biventricular support.

Unexpected Abrupt Increase in Left Ventricular Assist Device Thrombosis

BACKGROUND We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (±SD) age of the patients was 55±14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

Low Thromboembolism and Pump Thrombosis With the HeartMate II Left Ventricular Assist Device: Analysis of Outpatient Anti-coagulation

BACKGROUND The HeartMate II (Thoratec, Pleasanton, CA) is an effective bridge to transplantation (BTT) but requires anti-coagulation with warfarin and aspirin. We evaluated the risk of thromboembolism and hemorrhage related to the degree of anti-coagulation as reflected by the international normalized ratio (INR). METHODS INRs were measured monthly for 6 months in all discharged HeartMate II BTT patients and at an event. Each INR was assigned to ranges of INRs. Adverse events analyzed were ischemic and hemorrhagic stroke, pump thrombosis, and bleeding requiring surgery or transfusion. Events were correlated to the INR during the event and at the start of the month. RESULTS In 331 patients discharged on support, 10 had thrombotic events (9 ischemic strokes, 3 pump thromboses), and 58 had hemorrhagic events (7 strokes, 4 hemorrhages requiring surgery, and 102 requiring transfusions). The median INR was 2.1 at discharge and 1.90 at 6 months. Although the incidence of stroke was low, 40% of ischemic strokes occurred in patients with INRs < 1.5 and 33% of hemorrhagic strokes were in patients with INRs > 3.0. The highest incidence of bleeding was at INRs > 2.5. CONCLUSIONS The rate of thromboembolism during long-term outpatient support with the HeartMate II is low. The low number of thrombotic events appears to be offset by a greater number of hemorrhagic events. An appropriate target INR is 1.5 to 2.5 in addition to aspirin therapy. In patients having recurrent episodes of bleeding, the risk of lowering the target INR appears to be small.

Transmural dispersion of repolarization in failing and nonfailing human ventricle.

Rationale: Transmural dispersion of repolarization has been shown to play a role in the genesis of ventricular tachycardia and fibrillation in different animal models of heart failure (HF). Heterogeneous changes of repolarization within the midmyocardial population of ventricular cells have been considered an important contributor to the HF phenotype. However, there is limited electrophysiological data from the human heart. Objective: To study electrophysiological remodeling of transmural repolarization in the failing and nonfailing human hearts. Methods and Results: We optically mapped the action potential duration (APD) in the coronary-perfused scar-free posterior-lateral left ventricular free wall wedge preparations from failing (n=5) and nonfailing (n=5) human hearts. During slow pacing (S1S1=2000 ms), in the nonfailing hearts we observed significant transmural APD gradient: subepicardial, midmyocardial, and subendocardial APD80 were 383±21, 455±20, and 494±22 ms, respectively. In 60% of nonfailing hearts (3 of 5), we found midmyocardial islands of cells that presented a distinctly long APD (537±40 ms) and a steep local APD gradient (27±7 ms/mm) compared with the neighboring myocardium. HF resulted in prolongation of APD80: 477±22 ms, 495±29 ms, and 506±35 ms for the subepi-, mid-, and subendocardium, respectively, while reducing transmural APD80 difference from 111±13 to 29±6 ms (P<0.005) and presence of any prominent local APD gradient. In HF, immunostaining revealed a significant reduction of connexin43 expression on the subepicardium. Conclusions: We present for the first time direct experimental evidence of a transmural APD gradient in the human heart. HF results in the heterogeneous prolongation of APD, which significantly reduces the transmural and local APD gradients.

Randomized, Double-Blind Trial of Inhaled Nitric Oxide in LVAD Recipients With Pulmonary Hypertension

BACKGROUND Pulmonary vascular resistance is often elevated in patients with congestive heart failure, and in those undergoing left ventricular assist device (LVAD) insertion, it may precipitate right ventricular failure and hemodynamic collapse. Because the effectiveness of inotropic and vasodilatory agents is limited by systemic effects, right ventricular assist devices are often required. Inhaled nitric oxide (NO) is an effective, specific pulmonary vasodilator that has been used successfully in the management of pulmonary hypertension. METHODS Eleven of 23 patients undergoing LVAD insertion met criteria for elevated pulmonary vascular resistance on weaning from cardiopulmonary bypass (mean pulmonary artery pressure > 25 mm Hg and LVAD flow rate < 2.5 L x min[-1] x m[-2]) and were randomized to receive either inhaled NO at 20 ppm (n = 6) or nitrogen (n = 5). Patients not manifesting a clinical response after 15 minutes were given the alternative agent. RESULTS Hemodynamics for the group at randomization were as follows: mean arterial pressure, 72 +/- 6 mm Hg; mean pulmonary artery pressure, 32 +/- 4 mm Hg; and LVAD flow, 2.0 +/- 0.3 L x min(-1) x m(-2). Patients receiving inhaled NO exhibited significant reductions in mean pulmonary artery pressure and increases in LVAD flow, whereas none of the patients receiving nitrogen showed hemodynamic improvement. Further, when the nitrogen group was subsequently given inhaled NO, significant hemodynamic improvements ensued. There were no significant changes in mean arterial pressure in either group. CONCLUSIONS Inhaled NO induces significant reductions in mean pulmonary artery pressure and increases in LVAD flow in LVAD recipients with elevated pulmonary vascular resistance. We conclude that inhaled NO is a useful intraoperative adjunct in patients undergoing LVAD insertion in whom pulmonary hypertension limits device filling and output.

An analysis of pump thrombus events in patients in the HeartWare ADVANCE bridge to transplant and continued access protocol trial

BACKGROUND The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. METHODS The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. RESULTS There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose ≤ 81 mg, international normalized ratio ≤ 2, and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile level of ≥ 3 at implant. CONCLUSIONS Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.

Infectious complications in patients with left ventricular assist device: etiology and outcomes in the continuous-flow era.

BACKGROUND Continuous-flow left ventricular assist devices (LVAD) are increasingly being used in patients with end-stage heart failure and have largely replaced older generation pulsatile devices. While significant rates of infection have been reported in patients with pulsatile device support, incidence and outcomes of this complication for the continuous-flow device patients remain unknown. METHODS Between June 2005 and August 2009, 81 patients were implanted with continuous-flow LVADs at Washington University School of Medicine either as bridge to transplantation or as destination therapy. Outcomes of this study included incidence of postimplantation infection, types of infection, microbiologic profile, and association of postimplantation infections with clinical endpoints. RESULTS Forty-two patients (51.9%) had at least one type of infection on continuous-flow LVAD support with a mean follow-up period of 9.2 ± 9.2 months. Patients who had an infection on LVAD support had a significantly prolonged hospital stay (37.9 ± 32.0 versus 20.7 ± 23.0 days, p = 0.008) and a trend toward increased mortality (33.1% versus 18.7% at 2 years, respectively, log rank p = 0.102) compared with patients who did not. Subgroup analysis revealed that postimplantation sepsis was significantly associated with increased mortality in the continuous-flow LVAD cohort (61.9% versus 18.0% at 2 years, respectively, in septic and nonseptic patients, log rank p = 0.001). The majority of the sepsis cases occurred before hospital discharge, whereas most of the device related infections occurred after discharge. Resistant Staphylococcus and Pseudomonas species were the most common pathogens leading to device- and nondevice-related local infections. Development of driveline or pocket infection had no effect on survival in patients with continuous-flow assist device support (p = 0.193). CONCLUSIONS Even though better clinical outcomes have been achieved with the newer generation continuous-flow devices, infection complications-in particular sepsis-are still a major risk for patients with continuous-flow LVAD implantation. Prevention strategies with aggressive medical and surgical management of infections may increase survival and decrease morbidity among continuous-flow LVAD patients.

Axial and centrifugal continuous-flow rotary pumps: A translation from pump mechanics to clinical practice

The recent success of continuous-flow circulatory support devices has led to the growing acceptance of these devices as a viable therapeutic option for end-stage heart failure patients who are not responsive to current pharmacologic and electrophysiologic therapies. This article defines and clarifies the major classification of these pumps as axial or centrifugal continuous-flow devices by discussing the difference in their inherent mechanics and describing how these features translate clinically to pump selection and patient management issues. Axial vs centrifugal pump and bearing design, theory of operation, hydrodynamic performance, and current vs flow relationships are discussed. A review of axial vs centrifugal physiology, pre-load and after-load sensitivity, flow pulsatility, and issues related to automatic physiologic control and suction prevention algorithms is offered. Reliability and biocompatibility of the two types of pumps are reviewed from the perspectives of mechanical wear, implant life, hemolysis, and pump deposition. Finally, a glimpse into the future of continuous-flow technologies is presented.