Allen S. Anderson

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.

Gene-Expression Profiling for Rejection Surveillance after Cardiac Transplantation

BACKGROUND Endomyocardial biopsy is the standard method of monitoring for rejection in recipients of a cardiac transplant. However, this procedure is uncomfortable, and there are risks associated with it. Gene-expression profiling of peripheral-blood specimens has been shown to correlate with the results of an endomyocardial biopsy. METHODS We randomly assigned 602 patients who had undergone cardiac transplantation 6 months to 5 years previously to be monitored for rejection with the use of gene-expression profiling or with the use of routine endomyocardial biopsies, in addition to clinical and echocardiographic assessment of graft function. We performed a noninferiority comparison of the two approaches with respect to the composite primary outcome of rejection with hemodynamic compromise, graft dysfunction due to other causes, death, or retransplantation. RESULTS During a median follow-up period of 19 months, patients who were monitored with gene-expression profiling and those who underwent routine biopsies had similar 2-year cumulative rates of the composite primary outcome (14.5% and 15.3%, respectively; hazard ratio with gene-expression profiling, 1.04; 95% confidence interval, 0.67 to 1.68). The 2-year rates of death from any cause were also similar in the two groups (6.3% and 5.5%, respectively; P=0.82). Patients who were monitored with the use of gene-expression profiling underwent fewer biopsies per person-year of follow-up than did patients who were monitored with the use of endomyocardial biopsies (0.5 vs. 3.0, P<0.001). CONCLUSIONS Among selected patients who had received a cardiac transplant more than 6 months previously and who were at a low risk for rejection, a strategy of monitoring for rejection that involved gene-expression profiling, as compared with routine biopsies, was not associated with an increased risk of serious adverse outcomes and resulted in the performance of significantly fewer biopsies. (ClinicalTrials.gov number, NCT00351559.)

Acute Heart Failure Syndromes: Emergency Department Presentation, Treatment, and Disposition: Current Approaches and Future Aims A Scientific Statement From the American Heart Association

With a prevalence of 5 800 000 (≈2% of the entire populace) in 2009 and an estimated yearly incidence of 550 000, the burden of heart failure (HF) in the United States is tremendous.1 Although HF is largely a condition defined by chronic debility, virtually all patients experience, at some point, acute symptoms that trigger a visit to the emergency department (ED). These symptoms may vary in severity but, for the most part, they necessitate early intervention, often with intravenous medication and, less frequently, respiratory support. As shown by combined data from the National Ambulatory Medical Care Survey (NAMCS) and the National Hospital Ambulatory Medical Care Survey (NHAMCS), this is a common occurrence; there are nearly 658 000 annual ED encounters primarily for acute HF in the United States—a figure that represents almost 20% of the total HF-specific ambulatory care delivered each year.2 It is noteworthy that few settings other than the ED can offer open access to treatment or provide the level and intensity of care required to effectively manage the acute phase of decompensation, also referred to as episodes of acute heart failure syndromes (AHFS). Nearly 80% of those treated for AHFS in the ED are ultimately admitted to the hospital and, accordingly, the ED serves as the principal portal of entry for hospitalized AHFS patients.34 The ED therefore plays a unique role in the continuum of AHFS treatment, functioning for most patients as the initial point of definitive healthcare contact, the location where primary stabilization is achieved, and the site where disposition decisions are generally made.4 Whereas the ED is a pivotal place for the vast majority of hospitalized patients with acute HF, the evidence base on which this foundation of acute care is built is astonishingly thin. The purpose of this …

Intrapericardial Left Ventricular Assist Device for Advanced Heart Failure.

Background Mechanical circulatory support with a left ventricular assist device (LVAD) is an established treatment for patients with advanced heart failure. We compared a newer LVAD design (a small intrapericardial centrifugal‐flow device) against existing technology (a commercially available axial‐flow device) in patients with advanced heart failure who were ineligible for heart transplantation. Methods We conducted a multicenter randomized trial involving 446 patients who were assigned, in a 2:1 ratio, to the study (centrifugal‐flow) device or the control (axial‐flow) device. Adults who met contemporary criteria for LVAD implantation for permanent use were eligible to participate in the trial. The primary end point was survival at 2 years free from disabling stroke or device removal for malfunction or failure. The trial was powered to show noninferiority with a margin of 15 percentage points. Results The intention‐to treat‐population included 297 participants assigned to the study device and 148 participants assigned to the control device. The primary end point was achieved in 164 patients in the study group and 85 patients in the control group. The analysis of the primary end point showed noninferiority of the study device relative to the control device (estimated success rates, 55.4% and 59.1%, respectively, calculated by the Weibull model; absolute difference, 3.7 percentage points; 95% upper confidence limit, 12.56 percentage points; P=0.01 for noninferiority). More patients in the control group than in the study group had device malfunction or device failure requiring replacement (16.2% vs. 8.8%), and more patients in the study group had strokes (29.7% vs. 12.1%). Quality of life and functional capacity improved to a similar degree in the two groups. Conclusions In this trial involving patients with advanced heart failure who were ineligible for heart transplantation, a small, intrapericardial, centrifugal‐flow LVAD was found to be noninferior to an axial‐flow LVAD with respect to survival free from disabling stroke or device removal for malfunction or failure. (Funded by HeartWare; ENDURANCE ClinicalTrials.gov number, NCT01166347.)

Cardiovascular complications of malignant carcinoid disease

Carcinoid tumors are endocrinologic malignancies often associated with a characteristic syndrome-the malignant carcinoid syndrome. Cardiovascular manifestations of this rare illness result from unique pathophysiologic characteristics, are associated with poor prognosis, and are difficult to treat medically. The hemodynamic consequences of this disease present unique management problems perioperatively. New pharmacologic and surgical therapies for malignant carcinoids have improved quality of life for patients to the extent that carcinoid heart disease now has more impact on morbidity and mortality rates. Cardiologists may be called on to diagnose and treat this rare cardiac disease. We review, for consulting cardiologists, the pathophysiologic characteristics, cardiovascular manifestations, and management of this disease.

Current State of Combined Heart–Liver Transplantation in the United States

BACKGROUND Combined heart-liver transplantation (CHLT) has been increasingly performed in the USA, but published data on overall patient and graft outcomes have been limited. METHODS This study aimed to review the indications, immunosuppression, complications and outcomes of CHLT in the USA. From October 1987 to December 2005, a total of 47 cases of combined heart-liver (n = 41) and heart-liver-kidney transplantation (n = 6) were reported to the United Network for Sharing (UNOS) database. One pediatric case was excluded from the analysis. The mean age of recipients was 46 years (range, 22 to 65 years) and included 31 (67%) men and 16 (33%) women. RESULTS The most common indication for both heart and liver transplantation was amyloidosis (30%). Patients were followed for a mean duration of 1,362 days or 3.7 years (range, 1 to 4,598 days or 0 to 12.6 years). Patient, heart and liver graft survival rates were 84.8%, 84.8% and 82.4% at 1 year, and 75.6%, 75.6% and 73.5% at 5 years, respectively. At the latest follow-up of patients who survived at least 6 months after transplantation (n = 39), 28.2% of patients were on a single immunosuppressive agent. CONCLUSIONS Combined heart-liver transplantation is a viable option for candidates who require the combined transplantation, with outcomes comparable to those of single-organ recipients.

Percutaneous Transcatheter Aortic Valve Closure Successfully Treats Left Ventricular Assist Device–Associated Aortic Insufficiency and Improves Cardiac Hemodynamics

OBJECTIVES This study sought to assess the effectiveness of a novel percutaneous method to treat left ventricular assist device (LVAD)-associated severe aortic insufficiency (AI) in a series of patients determined to be poor reoperative candidates. BACKGROUND The increased use of continuous-flow LVAD in advanced heart failure has led to marked changes in the management of patients with this condition. However, secondary AI can become a significant complication. METHODS Five patients with continuous-flow LVAD and severe post-LVAD AI underwent percutaneous transcatheter aortic valve closure from September to October 2011 at a single quaternary care academic medical center. All patients had LVAD implanted as destination therapy. LVAD parameters, hemodynamics, and echocardiographic measurements were obtained before and after aortic valve closure. RESULTS All patients underwent successful closure with the Amplatzer cribriform device (AGA Medical, Plymouth, Minnesota) via a percutaneous transcatheter femoral approach with a significant reduction of AI from severe to trivial. Cardiac hemodynamics improved, and the pulmonary capillary wedge pressure was reduced in all patients. There was no change in mitral or tricuspid regurgitation, LVAD power, or pulsatility index. CONCLUSIONS Percutaneous transcatheter closure of the aortic valve effectively treats LVAD-associated AI and reduces pulmonary capillary wedge pressure. This procedure should be considered to treat LVAD-associated AI in patients who are poor candidates for repeat operation. Further data are needed to assess long-term results.

TCT-379 Percutaneous Transcatheter Aortic Valve Closure Successfully Treats Left Ventricular Assist Device-Associated Aortic Insufficiency and Improves Cardiac Hemodynamics

The increased use of continuous-flow LVADs in advanced heart failure has led to marked changes in the management of patients with this condition. However, secondary AI can become a significant complication. Our objective was to assess the effectiveness of a novel percutaneous method to treat left

Risk assessment in pulmonary hypertension associated with heart failure and preserved ejection fraction

BACKGROUND Pulmonary hypertension (PH) is common in patients with left heart failure (HF), especially those with HF and preserved ejection fraction (HFpEF). However, there is limited data on risk stratification in these patients. METHODS Baseline clinical and hemodynamic variables of 339 patients with World Health Organization (WHO) Group 2 PH, 90% of whom had HFpEF, were studied to derive a multivariate Cox proportional hazards model. A simplified prognostic risk score was created based on the outcome of all-cause mortality. Nine predictors, significant after stepwise multivariable regression (p < 0.05), were used to create the risk score. Components of the risk score were functional class, diastolic blood pressure, pulmonary artery saturation, interstitial lung disease, hypotension on initial presentation, right ventricular hypertrophy, diffusion capacity of the lung for carbon monoxide, and 2 serum creatinine variables (≤ 0.9 mg/dl and ≥ 1.4 mg/dl). RESULTS Overall 2-year survival was 73.8% ± 2.4% in the derivation cohort, and 87.5% ± 2.3%, 66.4% ± 4.9%, and 24.4% ± 6.7% for risk scores of 0 to 2, 3 to 4, and 5+, respectively (p < 0.0001 for the trend), with a C-index of 0.76 (95% confidence interval [CI], 0.71-0.81). The risk score was validated in 2 independent PH-HFpEF cohorts: 179 patients with a C-index of 0.68 (95% CI, 0.55-0.80) and 117 patients with a C-index of 0.68 (95% CI, 0.53-0.83). For the 3 cohorts combined (N = 635), the overall C-index was 0.72 (95% CI 0.68-0.76). In all 3 cohorts individually and in the 3 cohorts combined, the risk score predicted death (hazard ratio, 1.4-1.6; p < 0.01). CONCLUSIONS Several clinical factors independently predict death in PH-HFpEF confirmed by validation. A novel risk score composed of these factors can be used to determine prognosis and may be useful in making therapeutic decisions.

SUCCESSFUL COMBINED LIVER-HEART TRANSPLANTATION IN ADULTS: REPORT OF THREE PATIENTS AND REVIEW OF THE LITERATURE

BACKGROUND Three patients received liver/heart transplantation, and we report their successful outcome. METHODS Two patients had alcoholic cirrhosis and dilated cardiomyopathy; one had cryptogenic liver disease and idiopathic cardiomyopathy. RESULTS All patients had evidence of portal hypertension and coagulopathy. The cardiac transplants were performed first. Cardiopulmonary bypass was discontinued in favor of venovenous bypass, and liver transplantation was then performed. All patients developed acute tubular necrosis; two required a brief period of hemodialysis. There was only one episode of acute cellular rejection of the liver. Protocol endomyocardial biopsies in all three patients revealed no evidence of rejection. All patients are currently using low doses of immunosuppressive medications and have normal liver chemistry tests and cardiac function; two patients have mild renal insufficiency. CONCLUSION In selected patients with severe cardiac dysfunction and advanced liver disease, liver/heart transplantation can be successfully performed even in the face of portal hypertension and coagulopathy.