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AHA 2013: Highlights of Interest to ISHLT Members

Rakesh K. Singh, MD
Assistant Professor of Pediatrics
Program for Pediatric Cardiomyopathy, Heart Failure and Transplantation
Columbia University
New York, New York, USA

Ryan J. Tedford, MD
Assistant Professor of Medicine
Heart Failure, Mechanical Circulatory Support and Cardiac Transplantation
Johns Hopkins University
Baltimore, Maryland, USA

Eugene C. DePasquale, MD
Clinical Instructor
Associate Director, Outpatient Heart Transplantation
Advanced Heart Failure, Heart Transplantation and Mechanical Circulatory Support Program
David Geffen School of Medicine at University of California, Los Angeles
Los Angeles, California, USA

The 2013 Scientific Sessions of the American Heart Association were held in Dallas, TX from November 16-20, 2013. The sheer size of the meeting makes it impossible to discuss all abstracts of importance for ISHLT members. Below are a few of the highlights from another great meeting.

Renal Optimization Strategies Evaluation in Acute Heart Failure (ROSE AHF) Trial
This multicenter, double-blind, placebo-controlled trial studied 360 hospitalized patients with acute heart failure and renal dysfunction randomizing these patients, compared to placebo, in a 1:1 allocation ratio the addition of low dose dopamine (2mcg/kg/min) or low-dose nesiritide (0.005 mcg/kg/min) to diuretic therapy and whether decongestion is enhanced and renal function is preserved. Within each strategy, there was a 2:1 ratio to active treatment or placebo. Coprimary endpoints included 72-hour cumulative urine volume (decongestion endpoint) and change in serum cystatin C to 72 hours (renal function endpoint). Ultimately neither strategy enhanced decongestion or improved renal function when added to diuretic therapy.
JAMA 2013; doi:10.1001/jama.2013.282190

Mitral-Valve Repair versus Replacement for Severe Ischemic Mitral Regurgitation
This study randomized 251 patients with severe ischemic mitral regurgitation to undergo mitral-valve repair or chordal-sparing replacement in order to evaluate efficacy and safety. The primary endpoint was left ventricular end-systolic volume index at 12 months. There was no significant difference in left ventricular reverse remodeling or survival at 12 months between either strategies. The rate of moderate or severe recurrence of mitral regurgitation at 12 months was higher in the repair group than in the replacement group suggesting a more durable correction of mitral regurgitation with replacement. However, there was no significant between groups in outcomes.
NEJM; DOI: 10.1056/NEJMoa1312808

Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT)
In this randomized placebo controlled trial, patients with heart failure with preserved ejection fraction were randomized to spironolactone (titrated up to 45mg). Primary endpoint was time to first event mortality, aborted cardiac arrest or heart failure hospitalization. There was no significant difference in heart failure hospitalization, all-cause hospitalization or all-cause death. Compared with placebo the spironolactone group exhibited more hyperkalemia and were 50% more likely to experience doubling of creatinine above the upper limit of normal. This study failed to demonstrate a benefit in heart failure with preserved ejection fraction patients.

Diastolic Pulmonary Artery Pressure to Pulmonary Capillary Wedge Pressure Gradient (DPG) in over 5700 Patients with an Elevated Transpulmonary Gradient does Not Predict Survival after Cardiac Transplantation - Abstract 7084
(Tedford RJ, Beaty CA, Shah AS, et al.)

Using the United Network for Organ Sharing (UNOS) database, Tedford and colleagues from Johns Hopkins University studied the ability of the pre-transplant diastolic pulmonary gradient (diastolic pulmonary artery pressure minus pulmonary capillary wedge pressure) to predict survival after cardiac transplantation. All patients with pulmonary hypertension and an elevated transpulmonary gradient (n=5777) were included in the analysis. The results show no difference in survival between high (defined as >3, >5, >7, or >10mmHg) and low DPG groups (≤3, ≤5, ≤7, or ≤10mmHg), p = 0.94, 0.76, 0.29, 0.66, respectively. DPG did also not predict survival in those with pulmonary hypertension and an elevated pulmonary vascular resistance (PVR). The authors urge caution before DPG is incorporated into pre-transplant or pulmonary hypertension-related clinical decision making.

High Pre-Operative Right Atrial Pressure to Pulmonary Capillary Wedge Ratio is Not Associated with Right Ventricular Dysfunction After LVAD Implantation - Abstract 7086
(Cogswell RJ, Masri, SC)

Studying the pre- and post-LVAD hemodynamics of 69 patients, Cogswell and colleagues from the University of Minnesota found that an elevated right atrial pressure (RAP) to pulmonary capillary wedge pressure (PCWP) ratio did not predict right ventricular dysfunction after implantation. In fact, the tertile with the highest pre-LVAD RAP:PCWP ratios showed the greatest decline in RAP after LVAD implantation (p<0.0001). Overall, there was no difference in cardiac index, RAP, or PCWP in the three tertiles post-LVAD. This study suggests that an elevated RAP:PCWP ratio should not alone preclude LVAD implantation.

Incidence and Outcomes Related to Pre-Transplant Anti-Vimentin Antibodies in the Cardiac Transplantation Population - Abstract 5126
(Young R, Dale B, Tedford R, et. al.)

Young and colleagues from Johns Hopkins University analyzed 50 adult and pediatric patients who underwent de novo cardiac transplant for the presence of pre-transplant anti-vimentin antibodies (AVA). The incidence of AVA in pre-transplant samples was found to be high (34%). Pre-transplant AVA positivity did not predict rejection in the 1st year post-transplant, including time to first episode (31 vs. 13 days p=0.41) compared to AVA negative patients. There was no difference in rejection-free graft survival (53 vs. 52%, p=0.85), graft survival at 1 year (82 vs. 88%, p=0.56) or graft survival at a median follow up of 23 and 26 months (76 vs. 85%, p=0.41). The significance of pre-transplant AVA on outcomes should be validated in a larger cohort and with longer duration of follow-up.

Comparison of Difference Strategies of LVAD implantation for Bridging Patients to Heart Transplantation: An Analysis of the United Network for Organ Sharing - Abstract 5125
(Schulze PC, Kato ST, Mancini DM, et al)

Schulze and colleagues from Columbia University Medical Center utilized the UNOS database to study the impact of early versus late left ventricular assist device (LVAD) support on likelihood of successful heart transplant and post-transplantation outcomes. Patients (n=14,198) were classified into three groups: patients listed UNOS status 1A and 1B medically treated from the time of listing until heart transplantation (Group M), patients medically treated at listing but requiring LVAD implantation while listed (Group M-to-V), and patients on LVAD support at the time of listing for heart transplant (Group V). Patients on medical therapy had the highest waitlist mortality. Group M-to-V had similar waitlist mortality compared to Group V. Among the 1A status candidates Group M-to-V showed the highest likelihood of heart transplant (OR: 3.59 95% CI: 1.073-11.993; p=0.038). Post-transplant 1-year survival was worse in Group V compared to Group M (89.4% vs. 91.1% p=0.036). LVAD support at the time or during listing as a bridge to transplant was associated with lower waitlist mortality. The authors conclude that LVAD implantation in response to clinical deterioration during heart transplant listing is safe and not associated with increased mortality compared to patients with prior LVAD placement.

Echocardiographic Normalization in Children With Idiopathic Dilated Cardiomyopathy: Results From the Pediatric Cardiomyopathy Registry - Abstract 9783
(Everitt MD, Sleeper LA, Lu M, et al)

Everitt and colleagues analyzed the Pediatric Cardiomyopathy Registry (PCMR) database for the incidence and predictors of echocardiographic normalization of ventricular size and systolic function in children with idiopathic dilated cardiomyopathy (IDCM). The study cohort consisted of 773 children from 98 pediatric cardiac centers in the United States and Canada. Echo normalization occurred in 25% by 2 years, at a median of 9.4 months. About half (51%) of the cohort died or received a heart transplant by 2 years. Younger age (RR=0.9, 95% CI=0.86-0.94, p<0.001) and lower LVEDD z-score (RR=0.74, 95% CI=0.66-0.82, p<0.001) were independent predictors for normalization. Interestingly, 9 patients who had echo normalization within 2 years of diagnosis later went on to either die or undergo heart transplantation, suggesting that continued follow-up is needed in these children even after echo normalization.

Outpatient Milrinone Therapy as a Bridge to Pediatric Heart Transplantation: A Large Single Center Experience - Abstract 18457
(Auerbach SR, Cavanaugh J, Pietra B, et al)

Auerbach and colleagues from Children's Hospital Colorado presented a retrospective review of all their pediatric patients that have received outpatient milrinone between February 2000 and June 2013. A total of 53 patients were on milrinone as an outpatient as a bridge to heart transplantation. The median age was 9.7 years [IQR=2-16] and included infants with single ventricle physiology after failed stage 1 palliative surgery. The cardiac diagnoses included graft failure (n=17), dilated cardiomyopathy (n=16), congenital heart disease (n=15), and restrictive cardiomyopathy (n=5). The mean dose of milrinone was 0.5+0.02 mcg/kg/min. There were few complications and all patients survived to transplantation, with a median duration of milrinone infusion of 28 days (IQR=2-16). This study supports the use of home milrinone therapy as a bridge to transplant, even in our youngest patients.

Use of Sirolimus in Pediatric Heart Transplant Patients: A Multi-Institutional Study From the Pediatric Heart Transplant Study Group - Abstract 11572
(Rossano JW, Jefferies JL, Pahl E, et al)

Rossano and his colleagues analyzed the Pediatric Heart Transplant Study (PHTS) registry for the use of sirolimus in pediatric heart transplant recipients. There were 2,085 patients from 46 pediatric heart transplant centers in the United States, Canada and England who underwent transplant between 2004 and 2010. Overall, 18% of patients were on sirolimus at some point (8% at 30 days post-transplant, 10% at 1 year, and 16% at 5 years). The use of sirolimus has increased over time, from 13% in 2005 to 17% in 2011 (p=0.02). Some factors associated with sirolimus use at 1 year included renal insufficiency and a history of rejection (p<0.05). Sirolimus treated patients had similar overall survival, 1-year conditional survival, and 5-year conditional survival in propensity matched analysis. Sirolimus use by 30 days post-transplant was associated with a decreased freedom from rejection (p=0.02) and infection (p=0.02), suggesting that early use of sirolimus may be associated with an increased risk of rejections and infections.

Disclosure Statement: the authors have no conflicts of interest to disclose.

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