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Background: Left ventricular assist devices are increasingly used to treat patients with advanced and otherwise refractory heart failure as bridge to transplant or destination therapy. We evaluated a new miniaturized left ventricular assist device that requires minimal surgery for implantation, potentially allowing implantation in earlier stage heart failure., Methods: HeartWare (Miami Lakes, Fla) developed transapical miniaturized ventricular assist device. Acute (n = 4), 1-week (n = 2), and 30-day (n = 4) bovine model experiments evaluated hemodynamic efficacy and biocompatibility of the device, which was implanted through small left thoracotomy with single insertion at apex of left ventricle without cardiopulmonary bypass. The device outflow cannula was positioned across the aortic valve. The international normalized ratio was maintained between 2.0 and 2.5 with warfarin. Hemodynamic, echocardiographic, fluoroscopic, hematologic, and blood chemistry measurements were evaluated., Results: The device was successfully implanted through the left ventricular apex in all 10 animals. The device was operated at 15,000 ± 1000 rpm (power consumption, 3.5-6.0 W). The device maintained normal end-organ perfusion with no significant hemolysis (0-30 mg/dL). There were no pump failures or device-related complications. At autopsy, no abnormalities were seen in endocardium, aortic valve leaflets, or aortic root. There was no evidence of thromboembolism or abnormalities in any peripheral end organs., Conclusions: We successfully demonstrated feasibility of a novel intraventricular assist device that can be completely implanted through left ventricular apex. This transapical surgical approach eliminates needs for sternotomy, device pocket, cardiopulmonary bypass, ventricular coring, and construction of an outflow graft anastomosis., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Preclinical hemolysis testing is a critical requirement toward demonstrating device safety for U.S. Food and Drug Administration (FDA) 510(k) approval of mechanical circulatory support devices (MCSD). FDA and ASTM (formerly known as the American Society for Testing and Materials) have published guidelines to assist industry with developing study protocols. However, there can be significant variability in experimental procedures, study design, and reporting of data that makes comparison of test and predicate devices a challenge. To overcome these limitations, we present a hemolysis testing protocol developed to enable standardization of hemolysis testing while adhering to FDA and ASTM guidelines. Static mock flow loops primed with fresh bovine blood (600 mL, Hematocrit = 27±5%, heparin titrated for ACT >300 sec) from a single-source donor were created as a platform for investigating test and predicate devices. MCSD differential pressure and temperature were maintained at 80 mmHg and 25°±2° C. Blood samples (3 ml) were collected at 0, 5, 90, 180, 270, 360 minutes to measure CBC and plasma free hemoglobin. This protocol led to 510(k) approval of two adult MCSD and has been used to test novel cannulae and a pediatric MCSD. Standardization of hemolysis testing procedures and transparency of results may enable better blood trauma characterization of MCS devices to facilitate the FDA 510(k) and PMA submission processes and improve clinical outcomes.

Objective: Thromboembolic events have been observed in heart failure (HF) patients supported by long-term mechanical circulatory support (MCS) devices. It has been hypothesized that these adverse events may be the result of platelet activation associated with high rotational speeds common to axial flow pumps. In this study, markers of platelet activation were investigated in HF patients supported by a HeartMate II left ventricular assist device (LVAD)., Methods: The study group consisted of 34 HF patients supported by a HeartMate II axial flow LVAD implanted for destination therapy (DT). This patient population was 94% male (31 M, 3 F), supported by LVAD for 30 to 723 days (average 268 days), and with an anticoagulation regimen of Coumadin (0-8 mg daily dose) and aspirin (0-325 mg daily dose). Platelet adhesion markers (soluble P-selectin and solube CD40 ligand), platelet count (PC), hematocrit (Hct), and creatinine (Cr) were measured., Results: The soluble P-selectin marker was within normal platelet activity limits for all end points. The soluble CD40 ligand marker indicated platelet inactivity for all end points. Despite high shear stresses associated with a high-speed axial flow pump, the HeartMate II had no discernable effect on platelet activation. Current clinical doses of aspirin also appear to have little effect on platelet activation. Platelet count, hematocrit, and creatinine were normal in these patients over duration of support., Conclusions: There were no discernable changes in platelet activation markers soluble P-selectin and soluble CD40 ligand in HF patients support by HeartMate II LVAD independently of length of support, anti-platelet, and anti-coagulation regimens.

Purpose of Review: Destination therapy with a left ventricular assist device (LVAD) has the potential to effectively treat a large number of patients with advanced heart failure who are not eligible for heart transplantation. With the advent of continuous-flow LVADs, safe and effective long-term circulatory support is available for properly identified candidates., Recent Findings: The highest mortality following LVAD implant is observed in the sickest patients (INTERMACS profile 1); therefore, there is an increasing trend toward selecting patients with INTERMACS profiles 2-5. The less-ill patients will be studied in the planned REVIVE-IT trial. The Heart Failure Survival Score, Seattle Heart Failure Model, and Destination Therapy Risk Score may provide guidance for patient selection and preoperative optimization therapy, but these tools need to be updated for current LVAD technology. The current 1-year survival rate for patients supported for destination therapy with a continuous-flow LVAD is 74%, which represents an increase of 6% since the clinical trial was completed 2 years ago., Summary: Substantial progress has been made concerning survival and quality of life since destination therapy was first introduced 10 years ago. Advances in patient selection, improved LVAD technology, and optimized treatment strategies provide much optimism for the treatment of more heart failure patients in the future.

Background: Patients listed for heart transplant have a prolonged wait time, with continued deterioration, poor quality of life, and 10% mortality. Although recent bridge to transplant (BTT) studies demonstrated 1-year survival similar to heart transplantation, doubt remains about overall effectiveness as a treatment strategy compared with waiting and implanting a left ventricular device (LVAD) only as a last resort. We evaluated 1-year outcome and effectiveness of LVAD vs heart transplantation., Methods: Patients on the heart transplantation list, either receiving an allograft or LVAD for BTT from January 2009 to December 2009 were evaluated. Of 43 patients treated, 1 received both LVAD and an allograft during same admission was removed from the analysis. All patients but one who received an allograft had prior LVAD. Descriptive and univariate (t test) statistics and Kaplan-Meier survival curve were used for analyses., Results: LVAD for BTT was used in 29 patients (51.4±12.8 years, 6.9% women), and 13 (51.1±11.6 years, 15.38% women) underwent heart transplantation. Initial hospital length of stay was 17.5±14.4 days in BTT group and 14.3±4.6 days in heart transplant group (p=0.44) At 1 year, the total number of days spent in the hospital (operation and related complications), including index hospitalization was 11.6±14.3 days/100 days in BTT and 7.9±9.0 days/100 days in heart transplantation (p=0.38). A total of 41% BTT and 46% heart transplant patients had one readmission within 3 months of the index hospitalization. Infection was the most common cause of readmission in both groups. The 1-year survival was similar for both groups (no hospital death in either group; 3 late deaths in the BTT group)., Conclusions: One-year outcomes for patients eligible for heart transplantation were similar whether they received an allograft or LVAD for BTT. Heart transplant outcome for patients with LVAD were not adversely affected. Improving outcomes for patients treated with LVAD suggest that current decision models for patients eligible for heart transplantation may need to be reevaluated., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Perioperative red blood cell transfusion is a risk factor for postoperative mortality and morbidity in coronary artery bypass grafting (CABG). Females have a higher risk of red blood cell transfusion, but few previous studies have accounted for preoperative hematocrit and female sex together as risk factors for red blood cell transfusion. We evaluated female sex as an independent risk factor for red blood cell transfusion in CABG, while accounting for hematocrit., Study Design: A cardiac surgery database was reviewed for isolated, primary, first-time CABG operations from a single center from January 2005 to June 2009. Demographic and clinical variables were evaluated as risk factors of red blood cell transfusion using univariate (Student t-test and chi-square test) and multivariate (logistic regression) analyses., Results: Of 2,107 patients (ALL-patients) reviewed, 640 had known hematocrit (KNOWN-Hct). Women had lower hematocrit (35.77% ± 4.07% vs 40.06% ± 4.79% for men). On multivariate analysis of ALL-patients, older age, smaller body surface area, and female sex were risk factors; higher ejection fraction and off-pump surgery were associated with less red blood cell transfusion. On multivariate analysis of KNOWN-Hct, older age, lower hematocrit, smaller body surface area, and lower ejection fraction were risk factors of red blood cell transfusion and sex was not a significant risk factor in this group., Conclusions: Female sex is not an independent risk factor for red blood cell transfusion in CABG when preoperative hematocrit is included as a covariate in a multivariable model. A lower hematocrit could explain some of the sex-specific disparities in outcomes after CABG and should be included in future analyses., (Copyright © 2011 American College of Surgeons. Published by Elsevier Inc. All rights reserved.)

The extent of hematologic effects of the new continuous flow left ventricular assist devices (CF-LVAD) has not been studied. Recent clinical studies have demonstrated that hemolysis and thrombosis are not common during CF-LVAD support, however, the incidence of bleeding remains a concern. The rate of postoperative bleeding is similar to that of the prior generation pulsatile LVAD, but gastrointestinal bleeding due to angiodysplasia and arteriovenous malformations is more common and appears to be related to the blood flow rheology of these devices. New evidence suggests that acquired von Willebrand's disease develops in some patients due to the reduction in high molecular weight (HMW) multimers of von Willebrand's factor (vWF). Similar to acquired von Willebrand's disease seen in patients with aortic stenosis, the shear stress of the CF-LVAD may cause proteolysis of the HMW multimers of vWF. In addition to acquired von Willebrand's disease, there is activation of the fibrinolytic system and a loss of platelet numbers and function during CF-LVAD support. The hematologic responses during CF-LVAD support are constantly changing, and antiplatelet therapy may need to be adjusted accordingly. Considerable research is needed to better define the complex hematologic effects during CF-LVAD support. Screening of patients for angiodysplasia and von Willebrand's disease before CF-LVAD implant may allow for effective preemptive treatment. Because bleeding causes significant morbidity for this population, more effective treatment strategies need to be developed.

Background: Rotary blood pumps used as left ventricular assist devices (LVADs) allow for long-term support and may become suitable alternatives to heart transplantation. Effects of this technology on the coagulation system are not completely understood, leading to controversial anticoagulation protocols. Thus, we investigated the primary hemostasis in patients with chronic LVAD therapy., Methods and Results: Twenty-six outpatients received axial flow LVAD (HeartMate II; Thoratec) for a median support time of 4.5 months. In a cross-sectional protocol, platelet aggregation in response to ADP and epinephrine, von Willebrand antigen (vWF:AG), and collagen-binding capacity (vWF:CB) were obtained. Von Willebrand factor (vWF) multimer analyses were performed, and patients were screened for bleeding events. This analysis was repeated after removal of the device for transplantation or recovery (n=12) and after a median of 15.5 months in ongoing patients (n=11). In all patients on devices, severe impairment of platelet aggregation as well as a loss of large vWF multimers were found. In 10 patients, a decreased vWF:CB/vWF:AG ratio was observed. Bleeding episodes occurred with an incidence of 0.17 per patient-year. After removal of the device, normal patterns of platelet aggregation, multimer analysis, and vWF:CB/vWF:AG ratio were recorded. In the second analysis of ongoing patients, impairment of platelet aggregation and loss of large vWF multimers were verified., Conclusions: A diagnosis of von Willebrand syndrome type 2 was established in all patients after LVAD implantation, and bleeding events confirmed this finding. Reversibility of this condition was found after removal of the device.

We report the first case of percutaneous radio-frequency (RF) ablation procedure in a patient implanted with a HeartMate II left ventricular assist device for refractory heart failure. This procedure was performed for poorly tolerated recurrent atrial arrhythmias. No harmful consequence happened during or after the procedure despite the potential electromagnetic interferences existing between the RF delivery and the functioning of the device.

Debate exists regarding the merits and limitations of continuous versus pulsatile flow mechanical circulatory support. To characterize the hemodynamic differences between each mode of support, we investigated the acute effects of continuous versus pulsatile unloading of the failing left ventricle in a bovine model. Heart failure was induced in male calves (n = 14). During an acute study, animals were instrumented through thoracotomy for hemodynamic measurement. A continuous flow (n = 8) and/or pulsatile flow (n = 8) left ventricular assist device (LVAD) was implanted and studied during maximum support ( approximately 5 L/min) and moderate support ( approximately 2-3 L/min) modes. Pulse pressure (PP), surplus hemodynamic energy (SHE), and (energy equivalent pressure [EEP]/mean aortic pressure (MAP) - 1) x 100% were derived to characterize hemodynamic energy profiles during the different support modes. Standard hemodynamic parameters of cardiac performance were also derived. Data were analyzed by repeated measures one-way analysis of variance within groups and unpaired Student's t-tests across groups. During maximum and moderate continuous unloading, PP, SHE, and (EEP/MAP - 1) x 100% were significantly decreased compared with baseline and compared with pulsatile unloading. As a result, continuous unloading significantly altered left ventricular peak systolic pressure, aortic systolic and diastolic pressure, +/-dP/dt, and rate x pressure product, whereas pulsatile unloading preserved a normal profile of physiologic values. As continuous unloading increased, the pressure-volume relationship collapsed, and the aortic valve remained closed. In contrast, as pulsatile unloading increased, a comparable decrease in left ventricular volumes was noted. However, a normal range of left ventricular pressures was preserved. Continuous unloading deranged the physiologic profile of myocardial and vascular hemodynamic energy utilization, whereas pulsatile unloading preserved more normal physiologic values. These findings may have important implications for chronic LVAD therapy.

Pulsatile flow left ventricular assist devices (PF-LVADs) have successfully supported patients with severe heart failure for bridge-to-transplant (BTT) and destination therapy (DT). End-organ dysfunction is often reversed, optimizing the patient's condition to enhance survival, and quality of life. Questions have been raised regarding the potential for continuous flow LVADs (CF-LVADs) to provide the same quality of circulatory support. Prior research showing that PF is superior to continuous, non-PF does not appear to be relevant with CF-LVADs for BTT and DT. Under most clinical conditions, arterial pulsatility is present during CF-LVAD support, and this type of support should not be termed "nonpulsatile." Clinical studies have shown that renal, hepatic, and neurocognitive function is either maintained within a normal range, or is significantly improved, during CF-LVAD support for durations up to 15 months. Results of the randomized clinical trial between the CF HeartMate II and the pulsatile HeartMate XVE (both by Thoratec Corp, Pleasanton, CA, USA) are pending final US Food and Drug Administration (FDA) review and are not yet published. Studies of microcirculation during CF-LVAD support indicate that capillary blood flow is adequate to support cellular function. There are anecdotal cases of patients being supported with a CF-LVAD for over seven years with preserved end-organ function. Presently, there are no clinical reports indicating that end-organ function is not well maintained. Current clinical evidence indicates that end-organ perfusion and function can be well maintained for extended durations of support with a CF-LVAD.

The miniaturization of mechanical assist devices and less invasive implantation techniques may lead to earlier intervention in patients with heart failure. As such, we evaluated the effectiveness of a novel, minimally invasive, implantable counterpulsation device (CPD) in augmenting cardiac function during impaired hemodynamics. We compared the efficacy of a 32-mL stroke volume CPD with a standard 40-mL intra-aortic balloon pump (IABP) over a range of clinically relevant pathophysiological conditions. Male calves were instrumented via thoracotomy, the CPD was anastomosed to the left carotid artery, and the IABP was positioned in the descending aorta. Hemodynamic conditions of hypertension, hypotension, and heart failure were pharmacologically simulated and data were recorded during CPD and IABP support (off, 1:2, 1:1 modes) for each condition. In all three pathophysiological conditions, the CPD and IABP produced similar and statistically significant (P < 0.05) increases in coronary artery blood flow normalized to the left ventricular (LV) workload. During hypotension and heart failure conditions, however, the CPD produced significantly greater reductions in LV workload and myocardial oxygen consumption as compared with the IABP. A novel 32-mL CPD connected to a peripheral artery produced equivalent or greater hemodynamic benefits than a standard 40-mL IABP during pharmacologically induced hypertension, hypotension, and heart failure conditions.

A growing population experiencing heart failure (100,000 patients/year), combined with a shortage of donor organs (less than 2200 hearts/year), has led to increased and expanded use of mechanical circulatory support (MCS) devices. MCS devices have successfully improved clinical outcomes, which are comparable with heart transplantation and result in better 1-year survival than optimal medical management therapies. The quality of perfusion provided during MCS therapy may play an important role in patient outcomes. Despite demonstrated physiologic benefits of pulsatile perfusion, continued use or development of pulsatile MCS devices has been widely abandoned in favor of continuous flow pumps owing to the large size and adverse risks events in the former class, which pose issues of thrombogenic surfaces, percutaneous lead infection, and durability. Next-generation MCS device development should ideally implement designs that offer the benefits of rotary pump technology while providing the physiologic benefits of pulsatile end-organ perfusion.

A totally implantable mechanical circulatory support system would be very desirable for destination therapy. However, implanting all components of a pulsatile total artificial heart (TAH) or left ventricular assist device (LVAD) is complex because of the requirement for a continuous electrical power supply and the need for volume compensation. Implantable compliance chambers were developed for early LVAD designs, and although they functioned properly during initial laboratory tests, air loss by diffusion and the development of fibrous tissue around the sac eventually rendered them ineffective. Because these problems have not yet been overcome, volume displacement LVADs are currently designed with either a direct communication to an external drive console or an atmospheric vent. Transcutaneous energy transmission systems (TETSs) were also developed, but because the skin was being penetrated for volume compensation, it seemed more efficient to transmit electrical power through wires incorporated into the venting apparatus. More recently, TETSs were used clinically for both a pulsatile TAH and LVAD in a small number of patients, but for reasons unrelated to the TETS, neither of these devices is presently in use. Because the newer continuous-flow LVADs do not require a compliance chamber, they present a potential future application for TETS technology, because infections of the percutaneous tube continue to be one of the most important limitations of long-term circulatory support. A totally implantable LVAD with an incorporated TETS for destination therapy could become an important advance in the treatment of end-stage heart failure.

The circadian rhythm of varying blood pressure and heart rate is attenuated or absent in patients with severe heart failure. In 28 patients supported by a left ventricular assist device (LVAD) for at least 30 days, a restoration of the circadian rhythm was demonstrated by a consistent nocturnal decrease, and then increase, of the LVAD flow while at a constant LVAD speed. The return of the circadian rhythm has implications for cardiac recovery, and the observation indicates that the continuous-flow LVAD has an intrinsic automatic response to physiologic demands., (Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: Anti-coagulation with heparin is often used after left ventricular assist device implantation as a transition to long-term warfarin therapy. We retrospectively evaluated the effects of heparin use on thromboembolic and bleeding complications after implantation of the HeartMate II left ventricular assist device (LVAD)., Methods: LVAD patients (n = 418) implanted as a bridge to transplant were divided into three groups: Group A patients (therapeutic, n = 118) received heparin and had a partial thromboplastin time (PTT) of >50 seconds on two or more occasions; Group B patients (sub-therapeutic, n = 178) had at least one PTT value in the range of 40 to 55 seconds; and Group C patients (no heparin, n = 122) had no PTT values >40 seconds. All patients were transitioned to warfarin and aspirin therapy. The following adverse events were evaluated: ischemic stroke; hemorrhagic stroke; pump thrombosis; bleeding requiring surgery; and bleeding requiring > or = 2 units of packed red blood cells in 24 hours., Results: There was no difference in the percentages of patients with ischemic (5%, 4%, 3%) or hemorrhagic (3%, 3%, 5%) strokes or pump thrombosis (3%, 2%, 2%) after post-operative day (POD) 3 among Groups A, B and C, respectively. From PODs 3 to 30, the percentage of patients requiring transfusion for bleeding was significantly lower for Group C (18%) than for Groups A (32%) and B (26%) (p = 0.04); differences after 30 days were not significant. Multivariate analysis revealed that post-operative heparin use, low post-operative platelet count and low baseline hematocrit value were independent risk factors for bleeding events between PODs 3 and 30., Conclusions: In patients receiving the HeartMate II LVAD who were directly transitioned to warfarin and aspirin therapy without intravenous heparin there was no short-term increase in risk of thrombotic or thromboembolic events, and bleeding requiring transfusion was significantly reduced. Additional long-term follow-up is needed to evaluate possible late effects., (Copyright 2010 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to assess the impact of continuous flow left ventricular assist devices (LVADs) on functional capacity and heart failure-related quality of life., Background: Newer continuous-flow LVAD are smaller and quieter than pulsatile-flow LVADs., Methods: Data from advanced heart failure patients enrolled in the HeartMate II LVAD (Thoratec Corporation, Pleasanton, California) bridge to transplantation (BTT) (n = 281) and destination therapy (DT) (n = 374) trials were analyzed. Functional status (New York Heart Association [NYHA] functional class, 6-min walk distance, patient activity scores), and quality of life (Minnesota Living With Heart Failure [MLWHF] and Kansas City Cardiomyopathy Questionnaires [KCCQ]) were collected before and after LVAD implantation., Results: Compared with baseline, LVAD patients demonstrated early and sustained improvements in functional status and quality of life. Most patients had NYHA functional class IV symptoms at baseline. Following implant, 82% (BTT) and 80% (DT) of patients at 6 months and 79% (DT) at 24 months improved to NYHA functional class I or II. Mean 6-min walk distance in DT patients was 204 m in patients able to ambulate at baseline, which improved to 350 and 360 m at 6 and 24 months. There were also significant and sustained improvements from baseline in both BTT and DT patients in median MLWHF scores (by 40 and 42 U in DT patients, or 52% and 55%, at 6 and 24 months, respectively), and KCCQ overall summary scores (by 39 and 41 U, or 170% and 178%)., Conclusions: Use of a continuous flow LVAD in advanced heart failure patients results in clinically relevant improvements in functional capacity and heart failure-related quality of life., (Copyright (c) 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Continuous-flow left ventricular assist devices (LVAD) have emerged as the standard of care for advanced heart failure patients requiring long-term mechanical circulatory support. Evidence-based clinical management of LVAD-supported patients is becoming increasingly important for optimizing outcomes. In this state-of-art review, we propose key elements in managing patients supported with the new continuous-flow LVADs. Although most of the presented information is largely based on investigator experience during the 1,300-patient HeartMate II clinical trial, many of the discussed principles can be applied to other emerging devices as well. Patient selection, pre-operative preparation, and the timing of LVAD implant are some of the most important elements critical to successful circulatory support and are principles universal to all devices. In addition, proper nutrition management and avoidance of infectious complications can significantly affect morbidity and mortality during LVAD support. Optimizing intraoperative and peri-operative care, and the monitoring and treatment of other organ system dysfunction as it relates to LVAD support, are discussed. A multidisciplinary heart failure team must be organized and charged with providing comprehensive care from initial referral until support is terminated. Preparing for hospital discharge requires detailed education for the patient and family or friends, with provisions for emergencies and routine care. Implantation techniques, troubleshooting device problems, and algorithms for outpatient management, including the diagnosis and treatment of related problems associated with the HeartMate II, are discussed as an example of a specific continuous-flow LVAD. Ongoing trials with other continuous-flow devices may produce additional information in the future for improving clinical management of patients with these devices., (Copyright 2010 Elsevier Inc. All rights reserved.)

Left ventricular assist devices (LVADs) are slowly gaining acceptance as the treatment of choice in appropriately selected patients with end-stage heart failure who are not transplant candidates. Obesity is a well-known risk factor for increased cardiovascular morbidity and mortality, and frequently can be the reason some patients are turned down for heart transplantation. Because of this experience in transplant patients, many centers have also been reluctant to offer these patients an LVAD for destination therapy (DT). Subsequently, the 1-year outcomes of obese patients receiving LVADs for DT at our center were reviewed. Fifty-eight consecutive patients (83% men) were implanted with HeartMate XVE (n = 22) or HeartMate II (n = 36) LVAD. Patients were divided into normal (body mass index [BMI] or= 30 kg/m(2), n = 20) groups according to their BMI. Preoperatively, there were statistically significant differences (P < 0.05) between normal and obese groups in age (65.9 years vs. 54.7 years), weight (72.9 kg vs. 107.5 kg), BMI (24.1 kg/m(2) vs. 35.2 kg/m(2)), and incidence of diabetes (37% vs. 60%). At 1-year follow-up, there were no statistically significant differences (P > 0.5) between normal and obese groups: creatinine levels (1.4 vs. 1.5), New York Heart Association classification (1.2 vs. 1.6), and survival (63% vs. 65%). Our initial results demonstrate that morbidly obese patients with end-stage heart failure with a contraindication for transplant may successfully undergo implantation of an LVAD for DT.

Background: Patients with advanced heart failure have improved survival rates and quality of life when treated with implanted pulsatile-flow left ventricular assist devices as compared with medical therapy. New continuous-flow devices are smaller and may be more durable than the pulsatile-flow devices., Methods: In this randomized trial, we enrolled patients with advanced heart failure who were ineligible for transplantation, in a 2:1 ratio, to undergo implantation of a continuous-flow device (134 patients) or the currently approved pulsatile-flow device (66 patients). The primary composite end point was, at 2 years, survival free from disabling stroke and reoperation to repair or replace the device. Secondary end points included survival, frequency of adverse events, the quality of life, and functional capacity., Results: Preoperative characteristics were similar in the two treatment groups, with a median age of 64 years (range, 26 to 81), a mean left ventricular ejection fraction of 17%, and nearly 80% of patients receiving intravenous inotropic agents. The primary composite end point was achieved in more patients with continuous-flow devices than with pulsatile-flow devices (62 of 134 [46%] vs. 7 of 66 [11%]; P<0.001; hazard ratio, 0.38; 95% confidence interval, 0.27 to 0.54; P<0.001), and patients with continuous-flow devices had superior actuarial survival rates at 2 years (58% vs. 24%, P=0.008). Adverse events and device replacements were less frequent in patients with the continuous-flow device. The quality of life and functional capacity improved significantly in both groups., Conclusions: Treatment with a continuous-flow left ventricular assist device in patients with advanced heart failure significantly improved the probability of survival free from stroke and device failure at 2 years as compared with a pulsatile device. Both devices significantly improved the quality of life and functional capacity. (ClinicalTrials.gov number, NCT00121485.), (2009 Massachusetts Medical Society)

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.

Background: More than 400 patients with end-stage heart failure underwent left ventricular assist device (LVAD) implantation of LVAD as destination therapy (DT) after the US Food and Drug Administration approval of DT in 2002. Because most of these patients had surgeries at hospitals that were newly accredited, we sought to examine the impact of LVAD center volume on the outcomes of DT., Methods and Results: From July 1998 through December 2005, a total of 377 patients underwent implantation of HeartMate I LVAD as DT at 68 centers in the United States. Using data from the Thoratec DT Registry, we examined the association between LVAD center volume at the time of surgery and 1-year survival with DT. Of the studied 377 DT recipients, 53% underwent device implantation at centers that performed 9th DT implant; P=0.009). However, the DT center volume was not an independent predictor of 1-year survival with DT when adjusted for the preoperative DT Risk Score, suggesting that other factors, such as improved candidate selection, may have accounted for the institutional learning curve., Conclusions: The institutional experience with DT may have a significant impact on outcomes of this therapy. Better selection of candidates, systemic approach to surgical and postoperative care, as well as the long-term medical management most likely all contribute to these improvements.

Background: Direct measurement of blood flow output has been incorporated into ventricular assist devices (VADs), but long-term reliability of the additional device components has raised concerns regarding sensor drift and failure. As an alternative approach, the HeartMate II axial VAD (Thoratec Corp, Pleasanton, CA) estimates device flow output from power consumption and rotational speed of the device motor. This study evaluated the accuracy of HeartMate II flow estimation at the time of implantation., Methods: In 20 patients, intraoperative blood flow measurement of the HeartMate II flow estimator was compared with flow values obtained with an ultrasonic flow probe placed around the device outflow graft. Estimated and measured VAD flow data were simultaneously recorded and digitally stored while the device motor speed varied from 7,800 to 11,000 rpm and while achieving device flow outputs of 2 to 7 liters/min. Estimated and measured flows were compared using linear regression analyses and root mean square error., Results: HeartMate II flow estimation (FE) demonstrated a linear correlation with ultrasonic flow probe (FP) measurements: FE = 0.74 FP + 0.99 (R(2) = 0.56, p = 0.0001). A root mean square error of 0.8 liters/min was observed between flow estimation and direct flow measurement and suggests a 15% to 20% difference at flows of 4 of 6 liters/min., Conclusions: These results suggest that HeartMate II flow estimation may be used to provide directional information for trend purposes rather than absolute values of device blood flow output. Patient management should include but not be limited to this information.

Pulsatile ventricular assist devices have successfully provided circulatory support for many patients throughout the past quarter century; however, persistent complications have hindered expanded clinical application of this technology. Although the use of smaller, continuous-flow ventricular assist device pumps has reduced the frequency and severity of some adverse events, design enhancement may further improve outcomes for patients who require long-term left ventricular support. One new product, the HeartWare, Inc., miniature ventricular assist device, features a wide-bladed rotor design in an axial-flow pump with a strong, passively suspended magnetic rotor. The operating range of 16,000 to 28,000 rpm can provide up to 10 L/min of flow. The wide blades portend minimal cellular trauma.This new device has not yet been approved for use in human beings. As a test, we implanted it in a calf, and we continuously monitored the device's performance and the hemodynamic results over 30 days. No mechanical failure occurred, and no thrombi were noted upon explantation of the device. The animal's circulation was stable during the test period, and no end-organ abnormalities were found upon autopsy. The potential benefits of this miniature ventricular assist device are its increased availability to a broader patient population, a lower risk of infection, simplified implantation procedures, and improved durability. Further in vivo testing is planned. Herein, we discuss the unique design of the HeartWare miniature ventricular assist device, our feasibility study of its performance, and the possibilities for its use in human beings.

Background: Advanced therapies for heart failure (HF), such as mechanical circulatory support (MCS) devices and xenotransplantation, are usually tested in bovine and porcine models. This approach assumes a priori that animal (patho)physiology will closely match that of humans. Systemic aortic input impedance (Z(ART)) is an important physiologic determinant of left ventricular (LV) performance. We tested the hypothesis that Z(ART) is lower in bovine and porcine than in humans with normal or failing hearts., Methods: High-fidelity aortic pressure and flow waveforms were recorded intra-operatively at native and paced heart rates of 100 beats per minute (bpm) in adult human patients with normal LV function (n = 13) or end-stage HF (n = 15), and normal calves (n = 10) and pigs (n = 18). Fast Fourier transformation was used to calculate Z(ART), and arterial resistance and compliance were estimated using a 4-element Windkessel model., Results: Humans with HF had greater Z(ART) than those with normal LV function, characterized by higher resistance (1.16 +/- 0.12 vs 1.00 +/- 0.10 mm Hg x s/ml, p < 0.05) and lower compliance (1.53 +/- 0.21 vs 1.88 +/- 0.33 ml x mm Hg, p < 0.05). Healthy calves and pigs had significantly lower resistance (calf: 0.63 +/- 0.07 mm Hg x s/ml; pig: 0.90 +/- 0.07 mm Hg x s/ml) and higher compliance (calf: 2.79 +/- 0.37 ml x mm Hg; pig: 2.80 +/- 0.64 ml x mm Hg) when compared to humans (p < 0.05) with normal or failing hearts., Conclusions: Z(ART) is significantly lower in calves and pigs than in humans with or without HF. This finding has important implications for the pre-clinical testing of MCS devices and xenotransplants, which are usually examined in bovine and porcine models, respectively. Specifically, these therapies may respond differently in humans than animals due to non-equivalence of systemic after-load.

The acute hemodynamic efficacy of an implantable counterpulsation device (CPD) was evaluated. The CPD is a valveless single port, 32-ml stroke volume blood chamber designed to be connected to the human axillary artery using a simple surface surgical procedure. Blood is drawn into the pump during systole and ejected during diastole. The acute hemodynamic effects of the 32-ml CPD were compared to a standard clinical 40-ml intra-aortic balloon pump (IABP) in calves (80 kg, n = 10). The calves were treated by a single oral dose of Monensin to produce a model of diminished cardiac function (DCF). The CPD and IABP produced similar increases in cardiac output (6% CPD vs. 5% IABP, p > 0.5) and reduction in left ventricular external work (14% CPD vs. 13% IABP, p > 0.5) compared to DCF (p < 0.05). However, the ratio of diastolic coronary artery flow to left ventricular external work increase from DCF baseline (p < 0.05) was greater with the CPD compared to the IABP (15% vs. 4%, p < 0.05). The CPD also produced a greater reduction in left ventricular myocardial oxygen consumption from DCF baseline (p < 0.05) compared to the IABP (13% vs. 9%, p < 0.05) despite each device providing similar improvements in cardiac output. There was no early indication of hemolysis, thrombus formation, or vascular injury. The CPD provides hemodynamic efficacy equivalent to an IABP and may become a therapeutic option for patients who may benefit from prolonged counterpulsation.

Particulate embolization remains a serious complication of cardiac surgery. Adverse events associated with particulate embolization affect patient morbidity and long-term survival, and increase the length of hospital stay and the cost of health care. Today, atherosclerosis plays a role in at least two-thirds of all adverse events after coronary artery revascularization, and postoperative stroke is the second most common cause of operative mortality. Because many lower-risk patients now undergo interventional revascularization, higher-risk patients are now typically referred for surgical revascularization. These patients are older and sicker, and have multiple comorbidities, making them more susceptible to adverse events. For these high-risk patients, surgeons should be proactive in attempting to reduce the possibility of emboli. Patients must be carefully assessed before surgery to determine their risk, and if the risk is high, surgeons should consider using newer, innovative devices, and techniques in their operative strategy that have proven to be effective in mitigating some of the potential embolic adverse events. A multifaceted, preventive strategy can make a difference, not only in reducing particulate emboli, but also in reducing morbidity and in lowering the economic burden on the health-care system. This brief review will address three areas of focus that are important for the prevention of particulate embolization: (i) prevalence and morbidity of atherosclerotic disease; (ii) risk factors for adverse neurologic events; and (iii) prevention/mitigation of adverse events for patients undergoing cardiac surgery.

Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) is the leading cause of in-hospital death for patients admitted with acute coronary syndromes. Expert guidelines for the care of AMI-CS patients recommend early revascularization with intra-aortic balloon pump support. Ventricular assist devices (VADs) offer the advantages of providing greater and longer-term cardiac support than an intra-aortic balloon pump and may improve outcomes when inserted early after heart failure symptoms begin. Pulsatile VADs are versatile and can provide biventricular support but are associated with a higher incidence of serious complications. The newer percutaneous VADs can normalize cardiac index and can be implanted without surgery. Therefore, early implementation of percutaneous VADs and early revascularization may reduce the high mortality of AMI-CS. However, access to revascularization and VAD support, including percutaneous VADs, is currently limited and must improve to more effectively treat AMI-CS patients.

Sustained myocardial recovery and reversal of heart failure has been reported with the use of left ventricular assist devices (LVADs). However, clinical predictors of sustained recovery have not been clearly defined, and little information exists regarding exercise improvement in LVAD patients. Therefore, we sought to determine whether peripheral oxygen delivery and utilization were improved with LVAD support. Eleven patients with available pre- and post-LVAD cardiopulmonary exercise (CPX) data were studied retrospectively. Five patients received a HeartMate XVE for destination therapy (DT) and six patients received a Thoratec PVAD pneumatic LVAD for bridge-to-recovery (BTR). Oxygen uptake kinetics was assessed by fitting a single exponential function to the VO2 response. There was a significant improvement in several key parameters of cardiac performance including peak VO2, VO2 at anaerobic threshold (AT), oxygen kinetics as measured by mean response time (MRT), and oxygen deficit during LVAD support. Oxygen deficiency improved from 0.29 +/- 0.16 ml/kg to 0.16 +/- 0.06 ml/kg (p = 0.023), as did MRT 68 +/- 47.7 seconds to 35.8 +/- 13.3 seconds (p = 0.046) with LVAD support. Improved oxygen kinetics suggests improved peripheral utilization of oxygen, and may offer an additional clinical parameter to predict the likelihood of sustained recovery.

Results for Destination Therapy (DT) continue to improve with advanced technology, better patient selection, and experienced clinical management. Quality of life for these patients is an important component of the overall success of DT, and traveling is becoming more common. We reviewed our experience with long-distance travel in our DT population. All patients implanted with a left ventricular assist device for DT were followed prospectively. Long-distance travel was considered to be >200 miles, one way from their homes. There were 15 patients (14 men) with an average age of 66 years (range, 30-82) who traveled a combined total of 40 long-distance trips. Four trips were international (Spain, Canada (2), and Puerto Rico), 35 within the continental U.S., and one to Hawaii. The average one way distance traveled was 925 miles with a range of 218-4256 miles. The average time away from home was 8.3 days (range, 2-30). Patients traveled by airplane (17), car (23), and one trip included a 5 day cruise. Five complications occurred: driveline trauma, delay of reentry into the United States, missed flight, red heart alarm from bearing wear, and dehydration. All patients returned home safely for routine follow-up. Long-distance travel is possible for DT patients. Anticipating potential problems and careful planning is necessary for safe national and international travel.

The use of cardiopulmonary bypass (CPB) is associated with the development of a significant systemic inflammatory response syndrome (SIRS) which can affect patient outcomes. Multiple pathways are involved in initiating and maintaining SIRS. We studied whether a single dose of steroids (dexamethasone) after the induction of anesthesia could blunt the SIRS from CPB. A prospective, randomized, double-blinded, placebo control trial of 28 patients (13 study vs. 15 control). The study group received 100 mg of dexamethasone whereas the control group received sterile saline. Inclusion criteria were the following: elective coronary artery bypass grafting, less than 80 years old, normal ejection fraction, no acute myocardial infarction. Serum levels of C3a, interleukin (IL)-6, and plasma norepinephrine (PNE) were measured after intubation, 30 minutes after initiation of CPB, 24 and 72 hours after termination of bypass. The study group demonstrated significantly lower levels of IL-6 (p = 0.0005) at 24 hours and PNE (p = 0.05) at 72 hours post-CPB. There were no differences in the C3a levels between the groups. No infections occurred in either group. A single dose of dexamethasone reduces IL-6 and PNE levels associated with CPB. Despite the significant reductions in IL-6 and PNE, there was no effect on clinical outcomes. Additional studies are needed to demonstrate a clinically significant effect on patient outcomes.

Neurologic events during left ventricular assist device (LVAD) support are associated with significant morbidity and death. To evaluate this problem, we analyzed neurocognitive function and the frequency and incidence of neurologic events in 21 consecutive patients who were undergoing long-term support with the HeartMate XVE LVAD (Thoratec Corporation; Pleasanton, Calif). The mean duration of LVAD support was 531 days (range, 55-1, 309 d); the cumulative support time was 11,188 days (30.7 yr). No patients received anticoagulant therapy, and most received aspirin. None experienced strokes or transient ischemic attacks. Twenty patients were discharged from the hospital; 2 were later readmitted because of transient changes in neurologic status (metabolic encephalopathy) that ultimately resolved. Neurologic function, as measured by the National Institutes of Health Stroke Scale (NIHSS) and the Modified Rankin Score (MRS), was abnormal before LVAD implantation but normal 6 and 12 months after (mean NIHSS, 23.6 before vs 0 after; mean MRS, 0.68 before vs 0.18 after). Neurocognitive function, as evaluated by the Boston Naming Test, Trail Making Test part B, and Block Design Test, also improved during LVAD support. Together, these findings indicate that few neurologic events occur during long-term HeartMate XVE LVAD support in the absence of anticoagulation therapy. They also suggest that modifications made to the HeartMate LVAD since the REMATCH trial have resulted in fewer complications, and that better patient selection and supportive care have improved outcomes.

Human physiologic responses to pulsatile left ventricular assist devices (LVADs) are well understood; responses to the newer continuous flow pumps are not. Therefore, we evaluated the long-term effects of continuous flow LVAD support on fibrinolytic activation. Twelve recipients of an axial flow LVAD as destination therapy were assessed for fibrinolytic activation at 1, 3, 6, 9, and 12 months postimplantation. The fibrinolytic response and changes were assessed in terms of fibrinogen, D-dimer, plasma free hemoglobin, international normalized ratio (INR), and red blood cell (RBC) sedimentation rate. Bleeding and thromboembolic events were recorded. All fibrinolytic response parameters were elevated at baseline; mean RBC sedimentation rate was 51.8 mm/h, mean D-dimer was 3.95 nmol/L, and the mean fibrinogen was 356 mg/dl. The D-dimer and fibrinogen levels increased after LVAD implantation but returned to near-normal levels by 12 months. Red blood cell sedimentation rates increased indicating ongoing inflammation. Plasma free hemoglobin values decreased and remained low, an indicator of low shear rates and hemolysis. Three nonfatal bleeding events but no thromboembolic events were observed. Fibrinolytic responses initially increase after LVAD implantation but then gradually normalize.

The choice of replacement heart valve has alternated many times during the past 40 years. The reason for the change is related to the balance between prosthesis longevity and the need for anticoagulation therapy. Bioprosthetic valves do not require continuous anticoagulation therapy but their expected life can be less than the patient's. Anticoagulation therapy for mechanical valves carries the risk of bleeding or thromboembolism. Research shows progress toward a mechanical valve that has a reduced thrombotic risk which may reduce the anticoagulation therapy requirements. Patient self-management of anticoagulation therapy results in more effective therapy with lower doses of anticoagulants. The current trend is more frequent use of bioprosthetic valves; however, this trend may again reverse as therapy for mechanical valves is refined.

Background: As outcomes for destination therapy continue to improve, many patients are requiring left ventricular assist device (LVAD) exchange due to end-of-life of their LVAD. Current techniques to identify and diagnose device end-of-life issues usually require invasive testing or off-site filter dust analysis. In this study we assess a non-invasive technique using acoustic signals generated from the HeartMate XVE LVAD to potentially identify impending device end-of-life issues., Methods: Nine patients were prospectively followed after implantation of the HeartMate XVE LVAD as destination therapy between May 2004 and July 2006. Acoustic signals were collected using an aquatic hydrophone system interfaced with a data acquisition system and a standard laptop computer. Data were collected at pre-set intervals. All data/acoustic signals were prospectively interpreted by a blinded independent reviewer skilled at interpreting acoustic signals. Acoustic data suggesting possible device failure were then correlated with clinical findings and LVAD examination at the time of device removal., Results: All patients survived long enough to develop signs of impending device end-of-life. Four of 9 (44%) patients developed inflow valve incompetence, 4 (44%) were identified as having significant bearing wear, and 1 (12%) had both. All acoustically identified device issues were confirmed by standard clinical examinations and testing (echocardiography, angiography, laboratory tests and filter dust analysis). The acoustic findings were subsequently confirmed at time of device exchange. All patients ultimately had their device successfully exchanged and have continued to live with their new apparatus., Conclusions: Acoustic signal monitoring can successfully identify HeartMate XVE device end-of-life. This new method provides a low-cost, reproducible, non-invasive technique that may be used to identify possible impending device failure.

Objective: The Thoratec Implantable Ventricular Assist Device (Thoratec Corporation, Pleasanton, Calif) can be used for univentricular or biventricular support in patients with a body surface area as low as 1.3 m(2). Results of the multicenter clinical trial are reviewed., Methods: Between October 2001 and June 2004, a total of 39 patients at 12 institutions were supported with the Thoratec Implantable Ventricular Assist Device. Twenty-four patients (62%) received left ventricular assist devices and 15 (38%) received biventricular assist devices. Indications included bridge to transplantation (n = 30) and postcardiotomy failure (n = 9). The control group included 100 patients from the Food and Drug Administration approval submissions for the paracorporeal version of the ventricular assist device., Results: Twenty-eight male and 11 female patients, with mean age of 48 years (16-71 years) and body surface area of 1.9 m(2) (1.3-2.4 m2) were supported for 3938 patient-days (10.8 patient-years). Mean left ventricular assist device flow index on the first postoperative day was 2.5 +/- 0.5 L/(min x m2). Mean duration of support was 101 days (9-597 days). Eighteen patients were discharged after a mean duration of 96 days. There were no ventricular assist device failures. Complications included 13 cases of bleeding requiring reexploration (33.3%), 1 embolic and 2 hemorrhagic strokes (7.7%), 5 driveline infections (12.8%), and 2 pocket infections (5%). Support to successful outcomes was 70% for bridge to transplantation and 67% for postcardiotomy recovery, versus historical results for the paracorporeal ventricular assist device of 69% for bridge to transplantation and 48% for postcardiotomy recovery., Conclusion: The Thoratec Implantable Ventricular Assist Device is a new implantable pulsatile ventricular assist device that allows hospital discharge for patients as a bridge to transplantation or for postcardiotomy failure. It is the first Food and Drug Administration-approved implantable ventricular assist device with biventricular capability.

With the growing success and expanded use of ventricular assist devices, home discharge with independent ambulation and self-care are now important issues. We describe our initial home discharge experience with the Thoratec TLC-II portable drive. Patients discharged home were required to have five outpatient excursions (three monitored) before discharge and were seen weekly after discharge. Between August 2000 and December 2004, 14 patients (average age, 57 years) were placed on the TLC-II portable driver. One patient on the TLC-II portable driver had left ventricular assist device removal after 50 days of support but before discharge. Thirteen patients were discharged from the hospital with average time at home of 62 days (range, 16 to 243 days). After discharge, the TLC-II portable driver was maintained in the auto mode at average settings of 78 beat rate, 5.1 L/min flow rate, 204 mm Hg ejection pressure, and -8.4 mm Hg fill vacuum. A total of 5852 alarms (average, 6.7 per day) were recorded with 2373 battery reminders (41%), 1922 occlusion alarms during sleep (33%), and 1461 no-fill signals (25%). There were no readmissions for device malfunction, emergency battery utilization or back-up unit use. These results demonstrate that the Thoratec TLC-II portable driver is safe, reliable, and can be effectively managed at home.

Objective: We sought to investigate differences in indices of pulsatility between patients with normal ventricular function and patients with heart failure studied at the time of implantation with continuous-flow or pulsatile-flow left ventricular assist devices., Methods: Eight patients with normal ventricular function and 22 patients with heart failure were studied. A high-fidelity aortic and left ventricular pressure catheter was inserted retrograde through the aortic valve into the left ventricle, and transit-time flow probes were placed on the aorta and device outflow graft. Hemodynamic waveforms were recorded at native heart rate before cardiopulmonary bypass and over a range of device flow rates controlled by adjusting beat rate or rpm. These data were used to calculate vascular input impedance and 2 indices of vascular pulsatility: energy-equivalent pressure and surplus hemodynamic energy., Results: At low support levels, pulsatile support restored surplus hemodynamic energy to within 2.5% of normal values, whereas continuous support diminished surplus energy by more than 93%. At high support levels, pulsatile support augmented surplus energy by 49% over normal values, whereas continuous support further diminished surplus energy by 97%. Pulsatile support diminished vascular impedance from baseline failure values, whereas continuous support increased impedance. Vascular impedances at baseline for patients undergoing pulsatile and continuous support and during pulsatile support revealed normal vascular compliance, whereas impedance during continuous support indicated a loss of compliance (or "stiffening") of the vasculature., Conclusion: These results suggest that selection of device type and flow rate can influence vascular pulsatility and input impedance, which might affect clinical outcomes.

There are several methods for surgical management of aortic insufficiency in patients with end-stage congestive heart failure who are undergoing implantation of a left ventricular assist device (LVAD). To date, little is known about the long-term outcome of bioprosthetic valves for aortic insufficiency in patients with continuous flow LVADs. We report on two patients with bioprosthetic aortic valve replacement for aortic insufficiency at the time of HeartMate II LVAD insertion.

Background: The use of left ventricular assist devices (LVADs) as an alternative to transplant, or destination therapy (end of life support), is an increasingly important option for patients with end-stage heart failure. Prior studies have examined hospital costs for LVAD implants performed during investigational studies (e.g., REMATCH), but none has been published since that trial was completed., Methods: We performed a retrospective analysis of 23 consecutive patients who had a HeartMate XVE pump implanted as destination therapy at 2 high-volume ventricular assist device implant centers after US Food and Drug Administration approval in October 2003. We evaluated survival to discharge during the implantation hospitalization, hospital length of stay, and hospital costs, and compared them with outcomes reported from the REMATCH (RM) trial., Results: All patients in this cohort implanted post-REMATCH (PRM) had class IV heart failure and were similar in age, gender, and nearly all other pre-implantation clinical measures to the RM subjects. Mean hospital costs for PRM patients were 40% lower than for RM patients when measured from implantation to discharge (dollar 128,084 vs dollar 210,187, p < 0.01). PRM patients who survived implantation hospitalization had 48% lower costs than those who did not survive (dollar 114,979 vs dollar 215,456, p < 0.01), a finding similar to the RM experience. PRM patients in this cohort were more likely to survive to discharge compared with RM patients (87.0% vs 67.3%, p = 0.09). Mean hospital length of stay was 25% lower in the PRM group (44 vs 33 days) but did not reach statistical significance (p = 0.50)., Conclusions: Outcomes with use of LVADs as destination therapy have improved in the post-REMATCH era, including significantly lower hospital costs as well as strong trends toward better survival to hospital discharge and shorter average length of stay.

Clinical evidence of myocardial recovery in a small cohort of patients supported with a left ventricular assist device (LVAD) has been reported. Development of an optimal LVAD weaning protocol is needed for these patients to sustain recovery after device explant. In this study, we tested the hypothesis that LVAD stroke volume reduction produces a steady-state mechanical reloading of left ventricular (LV) pressures and volumes compared with LVAD rate reduction that results in transient mechanical reloading of the heart due to beat-to-beat variation in LV pressures and volumes. The relationship of LVAD flow to LVAD stroke volume and systolic interval over a range of LVAD rates (60, 80, 100, 120, and 140 bpm) was validated in a mock circulatory flow loop. In six acute experiments, calves were implanted with a pneumatic paracorporeal LVAD (PVAD, Thoratec, Pleasanton, CA). The PVAD was operated asynchronously in the auto volume mode (full decompression) for 30 minutes to establish a baseline control condition. The calf hearts were then mechanically reloaded by LVAD rate reduction (80, 60, and 40 bpm) or LVAD stroke volume reduction (100, 120, and 140 bpm) protocols consisting of 30 minutes of support at each LVAD beat rate. The order of weaning protocols was randomized with a 30-minute recovery period (LVAD volume mode to fully decompress heart allowing it to rest) between protocols to enable return to baseline control state. Aortic pressure and flow, LV pressure and volume, pulmonary artery flow, and LVAD flow waveforms were recorded for each test condition. The LVAD stroke volume reduction protocol produced steady-state mechanical reloading compared with VAD rate reduction that resulted in transient LV mechanical reloading. This distinction is due to differences in their temporal relationships between LVAD and LV filling and emptying cycles. The acute hemodynamic benefit of LVAD stroke volume reduction was greater reduction in LV end-diastolic pressure and increase in LV segmental shortening than LVAD rate reduction. The long-term effects of steady-state and transient LV mechanical reloading on myocardial structure and function toward achieving sustained myocardial recovery warrant further investigation.

Background and Aim of the Study: This ongoing, longitudinal, multi-center, North American study was designed to evaluate the safety and effectiveness of the On-X valve., Methods: The On-X valve was implanted in isolated aortic (AVR) and mitral (MVR) valve replacement patients at nine North American centers. Follow up was 98.6% complete. Anticoagulation compliance was evaluated by collection of international normalized ratio (INR) results in all patients throughout their postoperative follow up. Adverse events were recorded according to the AATS/STS guidance criteria. Hematologic studies were conducted postoperatively to evaluate hemodynamics and hemolysis., Results: In total, 142 AVR and 142 MVR implants were performed; the mean follow up was 4.5 years; total follow up was 1,273 patient-years (pt-yr). At implant, the mean patient age was 59.2 years (range: 28 to 85 years); 71.8% of patients who underwent AVR and 33.1% who underwent MVR were males. Preoperatively, 89.4% of AVR patients and 56.3% of MVR patients were in sinus rhythm. The cardiac disease etiology was primarily stenotic, calcific degeneration in AVR and rheumatic or degenerative regurgitation in MVR. Hemolysis represented by postoperative elevation of serum lactate dehydrogenase was very low (median 217 IU after AVR and 251 IU after MVR at one year (82% AVR and 98% MVR of upper normal). Late adverse event rates were low, most notably thromboembolism (0.9%/pt-yr after AVR; 1.6%/pt-yr after MVR) and thrombosis. Kaplan-Meier event-free rates at five years were correspondingly high. Anticoagulation compliance analysis showed only about 40% of INR readings to be within target ranges postoperatively; thus, the control range achieved was much greater than the desired target, as might generally be expected for clinic-controlled INR., Conclusion: The On-X valve performed well in this study, confirming the original design intent of minimal hemolysis and low adverse event rates.

We sought to evaluate the effectiveness of using an intra-aortic filtration system for the prevention of particulate emboli transport and the minimization of significant postoperative complications associated with particulate emboli. Between October of 2000 and October 2001, a total of 146 patients were enrolled at Advocate Christ Medical Center as part of the multi-institutional randomized trial (1289 patients at 22 centers). A total of 74 patients (51%) received the Embol-X intra-aortic filter and 72 patients (49%) were enrolled in the control group. Patients were evaluated for neurological deficit, myocardial infarction, renal insufficiency/failure, limb ischemia, and death at 12-hour, 24-hour, 72-hour, 7-day, and 30-day postoperative intervals. All filters received histological examination for particulate matter. Particulate matter was isolated in 70 (94.5%) of the filters successfully deployed. There was no statistically significant difference in the device related events between the filter and conventional cannulation groups (9/74 = 12.1% vs. 7/72 = 9.7%). Although not clinically evident, the primary event for both groups was ascending aortic intimal tears. There was one death in each of the groups not related to the filter or cannula used. The use of the Embol-X intra-aortic filter system has proven to be a safe and effective means to reduce the introduction of particulate emboli into the systemic circulation. Clearly, the reduction of particulate matter by as much as 95% justifies its use in cardiac surgery patients identified with an increased pre-operative embolic risk.

The Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure (REMATCH) trial demonstrated increased 1- and 2-year survival and improved quality of life for end-stage heart failure patients implanted with the HeartMate VE Left Ventricular Assist Device (LVAD) (Thoratec Corporation, Pleasanton, CA) compared with optimal medical management. This is the first report of Destination Therapy (DT) experience since REMATCH and incorporates improvements with the HeartMate XVE LVAD and patient management. Forty-two patients with end-stage heart failure at higher volume institutions were supported with the LVAD over a duration of 26.7 patient years (mean 232 days). Compared with REMATCH, DT patients had a 40% lower rate of death (0.49 vs. 0.84 deaths per patient year). Kaplan-Meier estimates of survival in the DT and REMATCH LVAD groups at 30 days were 90% and 81%, and at 1 year were 61% and 52%. The death rate due to sepsis was 8.3 times lower in DT patients (risk ratio, 0.12; 95% confidence interval, 0.02-0.90). DT patients were 2.1 times less likely to experience an adverse event (risk ratio, 0.47; 95% confidence interval, 0.35-0.63). These results demonstrate continued improvement with outcomes in long-term DT with LVADs. Given that these DT patients were similar to those in the REMATCH trial, the improved outcomes likely reflect improvements in the HeartMate XVE LVAD and experience with patient management.