Edwin C. McGee

Use of an Intrapericardial, Continuous-Flow, Centrifugal Pump in Patients Awaiting Heart Transplantation

Background— Contemporary ventricular assist device therapy results in a high rate of successful heart transplantation but is associated with bleeding, infections, and other complications. Further reductions in pump size, centrifugal design, and intrapericardial positioning may reduce complications and improve outcomes. Methods and Results— We studied a small, intrapericardially positioned, continuous-flow centrifugal pump in patients requiring an implanted ventricular assist device as a bridge to heart transplantation. The course of investigational pump recipients was compared with that of patients implanted contemporaneously with commercially available devices. The primary outcome, success, was defined as survival on the originally implanted device, transplantation, or explantation for ventricular recovery at 180 days and was evaluated for both noninferiority and superiority. Secondary outcomes included a comparison of survival between groups and functional and quality-of-life outcomes and adverse events in the investigational device group. A total of 140 patients received the investigational pump, and 499 patients received a commercially available pump implanted contemporaneously. Success occurred in 90.7% of investigational pump patients and 90.1% of controls, establishing the noninferiority of the investigational pump (P<0.001; 15% noninferiority margin). At 6 months, median 6-minute walk distance improved by 128.5 m, and both disease-specific and global quality-of-life scores improved significantly. Conclusions— A small, intrapericardially positioned, continuous-flow, centrifugal pump was noninferior to contemporaneously implanted, commercially available ventricular assist devices. Functional capacity and quality of life improved markedly, and the adverse event profile was favorable. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00751972.

Results of the Post-U.S. Food and Drug Administration-Approval Study With a Continuous Flow Left Ventricular Assist Device as a Bridge to Heart Transplantation: A Prospective Study Using the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support)

OBJECTIVES The aim of this study was to determine whether results with the HeartMate (HM) II left ventricular assist device (LVAD) (Thoratec Corporation, Pleasanton, California) in a commercial setting are comparable to other available devices for the same indication. BACKGROUND After a multicenter pivotal clinical trial conducted from 2005 to 2008, the U.S. Food and Drug Administration approved the HM II LVAD for bridge to transplantation (BTT). A post-approval study was required by the U.S. Food and Drug Administration to determine whether results with the device in a commercial setting are comparable to other available devices for the same indication. METHODS The study was a prospective evaluation of the first 169 consecutive HM II patients enrolled in the national INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) who were listed for transplant or likely to be listed. Patients were enrolled from April through August 2008 at 77 U.S. centers and followed for at least 1 year after implant. A comparison group (COMP) included all patients (n = 169 at 27 centers) enrolled in the INTERMACS registry with other types of LVADs (79% HeartMate XVE, 21% Implantable Ventricular Assist Device [Thoratec Corporation]) for the same BTT indication in the same time period. Survival rates, adverse events, and quality of life with the EuroQol EQ-5D visual analog scale were obtained in the INTERMACS registry. RESULTS Baseline characteristics were similar, but creatinine and blood urea nitrogen were lower in the HM II versus COMP groups, and there were fewer patients in the highest-risk INTERMACS patient profile Number 1 (24% for HM II vs. 39% for COMP). Adverse event rates were similar or lower for HM II versus COMP for all events. Bleeding was the most frequent adverse event for both groups (1.44 vs. 1.79 events/patient-year). Operative 30-day mortality for HM II was 4% versus 11% for COMP. The percentage of patients reaching transplant, cardiac recovery, or ongoing LVAD support by 6 months was 91% for HM II and 80% for COMP, and the Kaplan-Meier survival for patients remaining on support at 1 year was 85% for HM II versus 70% for COMP. Quality of life was significantly improved at 3 months of support and sustained through 12 months in both groups compared with baseline. CONCLUSIONS The results in a post-market approval, actual patient care setting BTT population support the original findings from the pivotal clinical trial regarding the efficacy and risk profile of the HM II LVAD. These data suggest that dissemination of this technology after approval has been associated with continued excellent results.

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.

HeartWare ventricular assist system for bridge to transplant: Combined results of the bridge to transplant and continued access protocol trial

BACKGROUND The HeartWare Ventricular Assist System (HeartWare Inc, Framingmam, MA) is a miniaturized implantable, centrifugal design, continuous-flow blood pump. The pivotal bridge to transplant and continued access protocols trials have enrolled patients with advanced heart failure in a bridge-to-transplant indication. METHODS The primary outcome, success, was defined as survival on the originally implanted device, transplant, or explant for ventricular recovery at 180 days. Secondary outcomes included an evaluation of survival, functional and quality of life outcomes, and adverse events. RESULTS A total of 332 patients in the pivotal bridge to transplant and continued access protocols trial have completed their 180-day primary end-point assessment. Survival in patients receiving the HeartWare pump was 91% at 180 days and 84% at 360 days. Quality of life scores improved significantly, and adverse event rates remain low. CONCLUSIONS The use of the HeartWare pump as a bridge to transplant continues to demonstrate a high 180-day survival rate despite a low rate of transplant. Adverse event rates are similar or better than those observed in historical bridge-to-transplant trials, despite longer exposure times due to longer survival and lower transplant rates.

Contemporary Perioperative Results of Isolated Aortic Valve Replacement for Aortic Stenosis

BACKGROUND Transcatheter aortic valve implantation may become a potential treatment for high-risk patients with aortic stenosis (AS). We analyzed our contemporary series of isolated aortic valve replacement (AVR) for AS to determine implications for patients referred for AVR. METHODS From April 2004 through December 2008, 190 patients (mean age, 68 years; 68% men) underwent isolated AVR for AS. Mean ejection fraction was 0.58. Sixty-one percent underwent minimally invasive AVR and 18% were reoperations. Twenty-one percent were aged 80 years or older, and 34% were in New York Heart Association functional class III-IV. Estimated operative mortality was 3.6%. RESULTS Thirty-day mortality was 0%. One in-hospital death (0.5%) occurred from complications of an esophageal perforation. Reoperation for bleeding occurred in 4.7%. Acute renal failure developed in 2.1%. Actuarial survival was 97% at 1 year and 94% at 3 years. Hospital length of stay was 7.0 days for patients aged 80 and older vs 5.0 days (p < 0.001), and they were less likely to be discharged to home (50% vs 83%, p < 0.001). CONCLUSIONS Contemporary results show that AVR for AS can be performed with low operative mortality and morbidity, although patients aged 80 years and older are at increased risk of prolonged recovery. Transcatheter aortic valve implantation may be an alternative for high-risk patients, but AVR is still appropriate for low-risk patients. The low risk of AVR supports the argument that asymptomatic patients who have a high likelihood of progression of AS may be considered for earlier surgical referral.

Cardiac Magnetic Resonance T2 Mapping in the Monitoring and Follow-up of Acute Cardiac Transplant Rejection A Pilot Study

Background—Acute rejection is a major factor impacting survival in the first 12 months after cardiac transplantation. Transplant monitoring requires invasive techniques. Cardiac magnetic resonance (CMR), noninvasive testing, has been used in monitoring heart transplants. Prolonged T2 relaxation has been related to transplant edema and possibly rejection. We hypothesize that prolonged T2 reflects transplant rejection and that quantitative T2 mapping will concur with the pathological and clinical findings of acute rejection. Methods and Results—Patients were recruited within the first year after transplantation. Biopsies were graded according to the International Society for Heart Lung Transplant system for cellular rejection with immunohistochemistry for humoral rejection. Rejection was also considered if patients presented with signs and symptoms of hemodynamic compromise without biopsy evidence of rejection who subsequently improved with treatment. Patients underwent a novel single-shot T2-prepared steady-state free precession 4-chamber and 3 short axis sequences and regions of interest were drawn overlying T2 maps by 2 independent blinded reviewers. A total of 74 (68 analyzable) CMRs T2 maps in 53 patients were performed. There were 4 cellular, 2 humoral, and 2 hemodynamic rejection cases. The average T2 relaxation time for grade 0R (n=46) and grade 1R (n=17) was 52.5±2.2 and 53.1±3.3 ms (mean±SD), respectively. The average T2 relaxation for grade 2R (n=3) was 59.6±3.1 ms and 3R (n=1) was 60.3 ms (all P value <0.05 compared with controls). The T2 average in humoral rejection cases (n=2) was 59.2±3.3 ms and the hemodynamic rejection (n=2) was 61.1±1.8 ms (P<0.05 versus controls). The average T2 relaxation time for all-cause rejection versus no rejection is 60.1±2.1 versus 52.8±2.7 ms (P<0.05). All rejection cases were rescanned 2.5 months after treatment and demonstrated T2 normalization with average of 51.4±1.6 ms. No difference was found in ventricular function between nonrejection and rejection patients, except in ventricular mass 107.8±10.3 versus 127.5±10.4 g (P < 0.05). Conclusions—Quantitative T2 mapping offers a novel noninvasive tool for transplant monitoring, and these initial findings suggest potential use in characterizing rejections. Given the limited numbers, a larger multi-institution study may help elucidate the benefits of T2 mapping as an adjunctive tool in routine monitoring of cardiac transplants.

Tricuspid valve repair with left ventricular assist device implantation: is it warranted?

BACKGROUND Tricuspid regurgitation is common in patients with advanced heart failure. The ideal operative strategy for managing tricuspid valve regurgitation (TR) in patients undergoing left ventricular assist device (LVAD) implantation is unclear. This study was designed to evaluate the effect on outcomes of concomitant tricuspid valve repair (TVR) for moderate to severe (3(+)/4(+)) TR at the time of LVAD implantation. METHODS Patients with >3(+) TR who underwent LVAD implantation from 2005 to 2009 were retrospectively evaluated. Pre-, intra- and post-operative data, including hemodynamics, inotrope requirements and end-organ function parameters, were considered. Outcomes of patients receiving TVR were compared with those who did not receive TVR (NTVR). RESULTS Seventy-two LVADs were implanted during the study period. Forty-two (58%) patients had ≥ 3(+) TR prior to LVAD implantation. Eight patients underwent TVR and 34 patients did not undergo TVR (NTVR). There were no significant differences in baseline characteristics or severity of TR between the two groups. The TVR group had a longer cardiopulmonary bypass time (p < 0.01) and required more blood products (p < 0.05). Higher post-operative creatinine and blood urea nitrogen (BUN) values were noted in the TVR group. One patient in the TVR group and 3 patients in the NTVR group required right-sided mechanical assistance (p = 0.6). There was no significant difference in short- or long-term mortality between the two groups. CONCLUSIONS TVR for ≥ 3(+) TR prolonged operative time and showed similar outcomes compared with LVAD implantation alone. A benefit of performing TVR was not demonstrated. As such, TVR may not be necessary at the time of LVAD implantation.

The HVAD Left Ventricular Assist Device: Risk Factors for Neurological Events and Risk Mitigation Strategies.

OBJECTIVES The purpose of this study was to determine the risk factors for ischemic in hemorrhage cerebrovascular events in patients supported by the HeartWare ventricular assist device (HVAD). BACKGROUND Patients supported with left ventricular assist devices are at risk for both ischemic and hemorrhagic cerebrovascular events. METHODS Patients undergoing implantation with a HVAD as part of the bridge-to-transplant trial and subsequent continued access protocol were included. Neurological events (ischemic cerebrovascular accidents [ICVAs] and hemorrhagic cerebrovascular accidents [HCVAs]) were assessed, and the risk factors for these events were evaluated in a multivariable model. RESULTS A total of 382 patients were included: 140 bridge-to-transplant patients from the ADVANCE (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure) clinical trial and 242 patients from the continued access protocol. Patients had a mean age of 53.2 years; 71.2% were male, and 68.1% were white. Thirty-eight percent had ischemic heart disease, and the mean duration of support was 422.7 days. The overall prevalence of ICVA was 6.8% (26 of 382); for HCVA, it was 8.4% (32 of 382). Pump design modifications and a protocol-driven change in the antiplatelet therapy reduced the prevalence of ICVA from 6.3% (17 of 272) to 2.7% (3 of 110; p = 0.21) but had a negligible effect on the prevalence of HVCA (8.8% [24 of 272] vs. 6.4% [7 of 110]; p = 0.69). Multivariable predictors of ICVA were aspirin ≤81 mg and atrial fibrillation; predictors of HCVA were mean arterial pressure >90 mm Hg, aspirin ≤81 mg, and an international normalized ratio >3.0. Eight of the 30 participating sites had established improved blood pressure management (IBPM) protocols. Although the prevalence of ICVA for those with and without IBPM protocols was similar (5.3% [6 of 114] vs. 5.2% [14 of 268]; p = 0.99), those with IBPM protocols had a significantly lower prevalence of HCVA (1.8% [2 of 114] vs. 10.8% [29 of 268]; p = 0.0078). CONCLUSIONS Anticoagulation, antiplatelet therapy, and blood pressure management affected the prevalence of cerebrovascular events after implantation of the HVAD. Attention to these clinical parameters can have a substantial impact on the occurrence of serious neurological events. (Evaluation of the HeartWare Left Ventricular Assist Device for the Treatment of Advanced Heart Failure [ADVANCE]; NCT00751972).

Midterm survival in patients treated for atrial fibrillation: A propensity-matched comparison to patients without a history of atrial fibrillation

OBJECTIVE Patients undergoing cardiac surgery with a history of untreated atrial fibrillation have reduced survival compared with similar patients without atrial fibrillation. We sought to compare the midterm survival of patients who received concomitant surgical ablation treatment for atrial fibrillation (atrial fibrillation ablated) with that of matched patients without a history of atrial fibrillation (no atrial fibrillation). METHODS We evaluated 3262 consecutive patients (813 [25%] with atrial fibrillation and 2449 [75%] without preoperative atrial fibrillation) undergoing cardiac surgery at a single institution from April 2004 to April 2009. Of patients with atrial fibrillation, 565 (70%) were treated with a concomitant surgical ablation procedure. Propensity scores were calculated on the basis of 37 known preoperative risk factors and yielded 744 patients. Midterm survival was compared between patients with atrial fibrillation ablation (n = 372) and patients without atrial fibrillation (n = 372). Survival was also compared between patients with successful vs unsuccessful ablation, and a matched analysis was performed at 1 year between the 2 groups. RESULTS Mean follow-up was 2.7 ± 1.6 years. Patients without atrial fibrillation and patients with treated atrial fibrillation had similar early 30-day mortality (1.2% vs 0.3%, P = .37) and overall mortality rates (11.6% vs 9.4%, P = .344), respectively. Survival analysis showed no differences at 1, 3, and 5 years between the 2 groups (log-rank P = .22). At last follow-up, 78% of treated patients were free of atrial fibrillation. At 1 year, 68% of patients were free of atrial fibrillation and antiarrhythmic medication. Freedom from atrial fibrillation and antiarrhythmic medication at 1 year predicted improved midterm survival (P = .03) compared with patients in atrial fibrillation or taking antiarrhythmic medication. Propensity-matched analysis after 1 year demonstrated improved survival for patients who were successfully treated (P = .016). CONCLUSIONS Patients undergoing surgical treatment of atrial fibrillation had survival similar to that of patients without a history of atrial fibrillation. Those with successful sinus restoration had improved survival compared with those who were treated but remained in atrial fibrillation.

Improvements in Health-Related Quality of Life Before and After Isolated Cardiac Operations

BACKGROUND Our study compared health-related quality of life (HRQOL) among cardiac surgical patient groups before and after cardiac operations for isolated surgical procedures and examined cardiac surgical patient HRQOL within the context of United States population norms. METHODS Of 2524 patients undergoing cardiac operations, 370 underwent isolated procedures (coronary artery bypass grafting, 136; aortic valve repair or replacement, 96; mitral valve repair or replacement, 92; Maze procedures, 46) between April 18, 2004, and June 30, 2008. They completed Short Form 36 questionnaires at baseline, at 3, 6, and 12 months postoperatively, and annually thereafter. Statistical analyses included χ(2), analysis of variance, longitudinal modeling, and longitudinal multivariable analyses. RESULTS Overall, the 370 cardiac surgical patients were 61.5 ± 11.9 years old, 70% men, and 76% white. Significant baseline differences in HRQOL existed among the cardiac surgical groups. Physical and mental components of the Short Form 36 improved from baseline to within 3 to 6 months postoperatively and remained stable through 3 years for all groups. When demographic and clinical covariates were held constant, the effect of cardiac surgical type on postsurgical HRQOL changes was not significant. CONCLUSIONS HRQOL improves early after cardiac operations and remains relatively constant long-term, independently of procedure type.