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AHA 2012:
Highlights of Interest to ISHLT Members

maryl johnson

ISHLT Links Senior Editor
Medical Director of Heart Failure and Transplantation
University of Wisconsin School of Medicine
Madison, Wisconsin, USA

The 2012 Scientific Sessions of the American Heart Association were held in Los Angeles, CA from November 3-7, 2012. Even for ISHLT members who attended, the size of the meeting makes it impossible to attend all sessions relevant to Advanced Heart Failure and Transplantation, so a summary of significant presentations is valuable for all ISHLT members. The size of the meeting also makes it impossible for one person to adequately summarize important studies that were presented. Therefore, I have solicited the assistance of other ISHLT members who attended the meetings to help compile a Top Hits list of presentations of interest and importance to ISHLT members. My sincere thanks to Eugene DePasquale, Kathy Grady, and Michael Kiernan, the behind the scenes reporters who helped compile these meeting highlights.

Three late breaking clinical trial presentations have the potential to significantly impact the care of patients with advanced heart disease including:

  1. CARRESS-HF (Cardiorenal Rescue Study in Acute Decompensated Heart Failure): This randomized trial, performed by the Heart Failure Clinical Trials Network and sponsored by the National Heart, Lung, and Blood Institute, compared ultrafiltration to stepped pharmacologic care in 188 patients admitted to the hospital with acute heart failure and worsened renal function, defined as an increase in creatinine of at least 0.3 mg/dl (26.5 micromoles/liter) in the 12 weeks before or 10 days following admission. Ultrafiltration offered no benefit in regards to weight loss at 96 hours compared to an intensive regimen of diuretics +/- vasodilator therapy. Ultrafiltration, however, resulted in worsening renal function. The CARRESS-HF study, therefore, does not support using this mechanical approach to fluid removal among patients who are responsive to diuretic therapy. This study has subsequently been published in the New England Journal of Medicine (NEJM 2012;367:2296-304).

  2. RELAX-HF (RELAXin in Acute Heart Failure): The RELAX-HF study compared the use of recombinant human relaxin 2 (seralaxin) and placebo in 1160 patients with acute heart failure. Seralaxin, compared to placebo, significantly improved signs and symptoms of heart failure at day 5. Seralaxin use was also associated with a 37% reduction in all-cause mortality at 6 months, although the overall event rate was small and thus the defined mortality benefit must be viewed cautiously. However, the study suggests that further evaluation of seralaxin use in patients with acute heart failure, for whom little evidence based therapy exists, is warranted.

  3. FREEDOM (Future Revascularization Evaluation in Patients with Diabetes Mellitus: Optimal Management of Multivessel Disease): The FREEDOM trial evaluated the relative benefits of coronary artery bypass grafting (CABG) and Drug Eluting Stent-Percutaneous Coronary Intervention (DES-PCI) in 1900 patients with multivessel CAD and diabetes mellitus. CABG patients had fewer composite outcomes (all-cause mortality, nonfatal MI or stroke) than DES-PCI patients (147 vs 205). All-cause mortality and myocardial infarction were independently decreased in the CABG patients, while stroke was slightly increased. Additionally, at 5 years, CABG improved quality adjusted life expectancy by approximately 0.03 years while increasing total costs by $3,600 per patient. This trial has also now been published in the New England Journal of Medicine (NEJM 2012;367:2375-84).

Additional presentations of interest to ISHLT members include the following:

  1. Cardiologist Involvement in Heart Failure Hospitalizations is Associated with Reduced Rates of Readmissions and Increased Severity of Illness.
    (Griffin A, Strauss C, Rutten-Ramos S, et al. Abstract #19554).

    Researchers from Abbott Northwestern Hospital, Minneapolis, MN reported a retrospective study of heart failure (HF) admissions in 2311 patients (median age 75 years), comparing characteristics and outcomes of HF patients cared for by cardiologists versus hospitalists. Patients cared for by cardiologists had more severe HF and increased costs of care than patients treated by hospitalists. Median hospital length of stay was similar between the groups, but, despite the increased severity of HF in patients cared for by cardiologists, HF readmissions were significantly reduced when an attending cardiologist managed inpatient care rather than an attending hospitalist (16% vs 27%, p<0.001). This suggests that the expertise of cardiologists is beneficial in decreasing readmissions for patients with HF, despite the increased severity of HF in such patients. It would have been nice if the study had defined how patients cared for by heart failure cardiologists fared compared to patients cared for by general cardiologists, but this analysis was not reported.

  2. Trends and Outcomes in Mechanical Circulatory Support Among Medicare Beneficiaries.
    (Khazanie P, Hammill BG, Eapen ZJ, et al. Abstract #19522).

    Investigators from Duke performed an analysis of 1835 Medicare patients who received mechanical circulatory support (MCS) from 2006 - 2010. A Cox proportional hazards model was used to examine temporal changes in mortality, readmission, and associated site volume of patients with heart failure who received an implantable VAD. Early and long term mortality decreased over time, in part due to increasing site volume. Better outcomes were noted at higher volume centers. Readmission decreased over time but remained common, indicating that continued improvement of the technology, processes of care and close management by VAD centers is needed.

  3. Ventricular Arrhythmias in Patients Following Continuous Flow Left Ventricular Assist Device Implantation.
    (Garan AR, Morrison K, Letarte L, et al. Abstract #19448).

    Investigators from Columbia presented a study designed to examine the need for internal cardioverter defibrillator (ICD) placement in patients with continuous flow left ventricular assist devices (LVADs). Of 69 patients with both an LVAD and ICD, 17.4% met the primary endpoint of hemodynamically significant ventricular arrhythmia or admission due to ventricular arrhythmia. Predictors of ventricular arrhythmia included ventricular arrhythmias prior to surgery and use of antiarrhythmic drugs. Patients with prior VT ablation and ischemic cardiomyopathy also tended to have more arrhythmic events. This study may serve to help develop an algorithm to identify those patients who truly warrant ICD implantation on MCS, a question commonly faced by MCS centers.

  4. Pre-Transplant Circulating Antibodies Predict Development of Antibody-Mediated Rejection after Heart Transplant Using the New ISHLT Antibody-Mediated Rejection Pathology Grading Scale.
    (Kittleson M, Patel J, Rafiei M, et al. Abstract #9369).

    Kittleson and colleagues from Cedars-Sinai presented a study of 106 patients designed to define whether an elevated pre-transplant peak PRA led to more antibody-mediated rejection (AMR) as assessed by the new ISHLT AMR grading scale. A PRA >10% increased the incidence of pathologic AMR and treated AMR in the first year. Although the results of the study might be considered to be "as expected", the study helps to identify transplant recipients in whom closer monitoring for AMR, and possibly pre-emptive treatment to prevent AMR (once an effective treatment has been defined) might be considered.

  5. Risk Factors for Long Term Morbidity After Pediatric Heart Retransplantation: Analysis from the International Society of Heart and Lung Transplantation Registry.
    (Conway J, Edwards LB, McCrindle BW, et al. Abstract #18474).

    ISHLT Registry data from 1998-2010 were analyzed to define risk factors for long term morbidities following retransplantation (ReTX) in patients receiving a primary transplant (PTX) at < 18 years of age. The analysis included 9248 PTX, 602 first ReTX, and 32 second ReTX. Several morbidities were more common in ReTX vs. PTX including allograft vasculopathy (AV) (HR 2.8), late rejection (HR 2.0), and late renal dysfunction (HR 2.6). Risk factors for AV after ReTX included pre-ReTX hypertension and AV as the indication for ReTX; donor hypertension, diabetes, cocaine use, and male donor to female recipient; and post-ReTX renal dysfunction, hospitalization for infection, and hypertension. Risk factors for late rejection after ReTX included CMV + recipient or donor, early rejection post-ReTX, documented non-compliance, and later year of ReTX. Risk factors for late renal dysfunction included higher pre-ReTX creatinine, later year of ReTX, dialysis post-ReTX, drug treated hypertension, development of AV, and hospitalization for infection. In a multivariate model, no associations were found between the duration of PTX and ReTX morbidities. Thus, ReTX in patients with PTX while in the pediatric age range is not only associated with inferior outcomes, but also with significant long term morbidities. Further analysis and attention to risk factors for common post-ReTX morbidities may improve recipient and donor selection for ReTX with the potential to improve outcomes.

  6. Outcomes after Pediatric Heart Transplantation with Use of the Berlin Heart EXCOR Pediatric Ventricular Assist Device.
    (Eghtesady P, Almond C, Tjossem C, et al. Abstract #11140).

    Although data suggests that the Berlin Heart EXCOR Pediatric VAD improves waiting list survival for pediatric heart transplant (PHT) candidates, little is known about how use of the EXCOR affects posttransplant outcomes. Data from 95 patients < 16 years of age implanted with the EXCOR from 10/07-11/11 were compared with a similarly aged Status 1A cohort (n=840) from the Organ Procurement and Transplant Network database from 5/07-12/10. Survival at one year posttransplant for the EXCOR group (87%) was similar to status 1A children not on VAD support at transplant (89%) and significantly better than patients on ECMO at transplant (60%). The most common causes of death posttransplant in the EXCOR group were rejection (50%), infection (17%), and stroke (17%). Survival of the EXCOR congenital heart disease patients was less than EXCOR cardiomyopathy patients, but similar to other OPTN Status 1A congenital heart disease patients. For patients that were transplanted off the EXCOR device, adverse events on the pump (infection, bleeding, and stroke) did not affect posttransplant survival.

Disclosure Statement: The author has no conflicts of interest to declare related to this meeting highlights report. The only disclosure is that many other noteworthy studies of interest to the ISHLT membership were presented at the American Heart meetings, but time and space do not allow them to be individually reported upon here.