Salpy V. Pamboukian

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

The presence of HLA-directed antibodies after heart transplantation is associated with poor allograft outcome.

Background. The clinical significance of HLA-directed antibodies newly detected after transplantation (HT) is controversial. Methods. Seventy-one HT recipients consented to enroll. Mean follow-up time was 28 months (range 6-48). Panel reactive antibody (PRA) analysis was performed on posttransplant sera (2 weeks, 1, 2, 3, 6, and 12 months and annually thereafter) using Flow-PRA. A mean of 6.9±1.2 serum samples per patient were obtained. Severity of cellular rejection was measured using the ISHLT grading system. Coronary angiography and intravascular ultrasound (IVUS) studies were performed annually to evaluate severity of allograft vasculopathy. Results. Twenty-five recipients had newly detected HLA-directed antibodies during the first year postHT. HLA class I antibodies were detected in 18 patients (25.4%), and class II in 11 patients (15.5%). The majority of donor recipient pairs were HLA mismatched (4.6±1.2 of the six major HLA antigens). Only mismatches at HLA-A locus had significant association with de novo posttransplant antibody formation. Length of ischemia time was correlated with early and sustained presence of de novo HLA-directed antibodies postheart transplant. Importantly, an association between de novo HLA-directed antibodies and cellular rejection was notes (P=0.0002). De novo HLA class II directed antibodies are also associated with IVUS documented vasculopathy (P<0.002). Finally, death due to allograft failure is associated with the presence of de novo formed HLA class II directed antibodies (P=0.008). Conclusions. Identifying the formation of de novo HLA-directed antibodies following heart transplantation may predict allograft outcome. This, in turn, may serve as a tool for individualization of immunosuppression protocols in heart transplant recipients.

Continuous-flow devices and percutaneous site infections: Clinical outcomes

BACKGROUND Although continuous-flow left ventricular assist device (LVAD) support has become standard therapy, the complexities of device and patient management remain a challenge. In particular, percutaneous site infections (PSI) are a serious complication during the post-implant course. We sought to study the incidence, risk factors, and clinical effect of PSI. METHODS Data were obtained from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) Registry. All adult patients who received a primary intracorporeal continuous flow LVAD between June 2006 and September 2010 were included. Descriptive statistics, Kaplan-Meier depictions, and multivariable analysis in the parametric hazard domain were used for statistical analysis. RESULTS A total of 239 PSIs were documented in 197 of 2,006 recipients (9.8%) of a continuous-flow LVAD. Mean follow-up was 8.1 months. Mean time to development of a PSI was 6.6 months. At 1 year after implant, nearly 19% of continuous-flow LVAD recipients developed a PSI. Multivariate analysis showed younger age (hazard ratio, 1.20; p < 0.0001) was the only factor predicting a PSI. Continuous-flow LVAD recipients who did not develop a PSI had improved survival (p = 0.004). Twenty-three patients died after development of a PSI. Sepsis was the most common cause of death (26.1%). CONCLUSIONS PSIs occur in approximately 19% of continuous-flow LVAD recipients by 12 months after implant. Young age is the only predictor of PSI. Importantly, development of a PSI adversely affects survival. Efforts to enhance driveline integration and to develop future totally implantable systems are warranted.

Comparison of outcomes in women versus men using a continuous-flow left ventricular assist device as a bridge to transplantation.

BACKGROUND The use of large, pulsatile left ventricular assist devices (LVADs) has been limited in women because of their small body size. METHODS We compared the survival outcomes, quality of life, and adverse events in 465 patients (104 women, 361 men) with advanced systolic heart failure in their first 18 months of support with the HeartMate II (Thoratec Corp, Pleasanton, CA) continuous-flow LVAD for bridge to transplantation. RESULTS During the first 18 months, there were no differences in survival between women and men while on LVAD support (73% ± 3% vs 73% ± 5%, p = 0.855) but fewer women (40%) underwent heart transplantation than did men (55%; p = 0.001). More women continued on support after 18 months (p = 0.007). Median duration of support was 238 days for women and 184 days for men (p = 0.003). Mortality was 20% for women and 19% for men (p = 0.89). Adverse events were similar, with the exception of hemorrhagic stroke, which occurred more frequently in women (0.10 vs 0.04 events/patient-year, p = 0.02), and device-related infections, which occurred less frequently in women (0.23 vs 0.44, p = 0.006). Functional capacity and quality of life at 6 months improved significantly in women and men. CONCLUSIONS Continuous-flow left ventricular assistance as a bridge to transplantation is associated with similar survival rates in women and men. Differences observed in higher stroke rates and fewer infections among women require further study.

Treprostinil-Based Therapy in the Treatment of Moderate-to-Severe Pulmonary Arterial Hypertension: Long-term Efficacy and Combination With Bosentan

BACKGROUND Treprostinil, a long-acting prostacyclin analog, diminished the symptoms of pulmonary arterial hypertension (PAH) in controlled 12-week clinical efficacy studies. This retrospective, single-center, open-label study was designed to assess the efficacy of long-term, subcutaneously administered, treprostinil-based therapy alone or in combination with bosentan for the treatment of moderate-to-severe PAH. METHODS Thirty-eight patients with pulmonary hypertension treated with subcutaneous treprostinil were followed up for a mean (+/-SD) duration of 984+/-468 days (range, 165 to 1,847 days). Oral bosentan was added to the treprostinil regimen if patients remained in New York Heart Association (NYHA) functional class III or II with intolerable prostacyclin side effects that limited therapy. Hemodynamic studies, Borg dyspnea score evaluations, 6-min walk (6MW) tests, and NYHA functional class determinations were performed at approximately 6-month intervals. RESULTS Mean pulmonary artery pressure decreased from 59.7 to 50.5 mm Hg (p<0.001). Significant and sustained improvement in 6MW distance (p=0.022) and Borg dyspnea score (p=0.023) were observed. At the final observation, the mean dose of treprostinil was 37.8 ng/kg/min (range, 7.5 to 115 ng/kg/min). At baseline, 5% of patients were in NYHA functional class 2 or lower vs 58% at the last follow-up. Bosentan was added to the regimens of 19 patients. In those patients, significant additional improvement occurred in the pulmonary arterial pressure (p<0.001), 6MW distance (p=0.001), and Borg dyspnea scale (p=0.020) compared to baseline. CONCLUSIONS Long-term treatment with subcutaneous treprostinil-based therapy improved functional parameters and hemodynamics in patients with moderate-to-severe PAH. In patients requiring combination therapy, the addition of oral bosentan to treprostinil-based therapy was safe, well-tolerated, and associated with further clinical improvements.

Minimizing infection and rejection death: Clues acquired from 19 years of multi-institutional cardiac transplantation data

BACKGROUND The purpose of this study was to estimate the relationship of age, race and gender to rejection and infection across time with respect to age at time of transplant, year of transplantation and immunosuppressive era. METHODS The study group consisted of 10,131 patients from 29 institutions in the Cardiac Transplant Research Database (n = 7,368, from 1990 to 2008) and 32 institutions in the Pediatric Heart Transplant Study (n = 2,763, from 1993 to 2008). The probabilities of rejection death and infection death were estimated with a parametric time-related model and adjusted for gender, ethnicity, date of transplant and age. RESULTS Actuarial survival by age at transplant showed that, when compared with the majority of patients transplanted between the ages of 30 to 60 years, death due to rejection at 5 years was highest among those transplanted at 10 to 30 years of age (p < 0.0001) and lowest in those transplanted at >60 years of age. Death due to infection at 5 years was highest among patients >60 years of age. Risk factors for death from rejection included age (p < 0.0001), female gender (p = 0.0001), black race (p < 0.0001) and transplant date (p < 0.0001); for infection death, risk factors were age (p < 0.0001), date of transplant (p < 0.0001), age (p = 0.002) and black race (p = 0.01). Modeling with respect to age at time of transplant showed an inverse relationship between infection and rejection death. Among patients transplanted at >60 years of age, there was a steep increase in infection-related deaths and a decrease in rejection deaths. Risk for rejection was elevated among young adults 10 to 30 years of age at time of transplant, particularly for black females. CONCLUSION Death from rejection affects adolescents and young adults preferentially, especially black recipients, whereas death from infection preferentially affects patients >60 years of age. Relative risk of infection vs rejection death with respect to recipient age should be considered in therapeutic plans for recurrent rejection, particularly in adolescents and the elderly.

Safety and accuracy of a wireless pulmonary artery pressure monitoring system in patients with heart failure.

BACKGROUND Implantable hemodynamic monitoring to guide heart failure (HF) therapy is a promising area of active research. The goal of this investigation was to evaluate the safety and technical performance of a novel wireless pulmonary artery pressure monitoring system in 17 patients with symptomatic HF. METHODS The monitoring system consists of a sensor, delivery catheter, interrogator, and home monitoring device. The HF sensor was implanted into a distal branch of the pulmonary artery. Pulmonary artery pressures were monitored using the external device, which powers the HF sensor and transmits the hemodynamic data from the patients home to a secure Internet database. The accuracy of the system was assessed by comparison with standard right heart catheterization (RHC). RESULTS The HF sensor was safely and successfully implanted in all patients. Agreement between the HF sensor and RHC for systolic, diastolic, and mean pulmonary artery pressures was excellent, with correlation coefficients of 0.94, 0.85, and 0.95, respectively (all P < .0001). Using Bland-Altman plots, the average differences for systolic, diastolic, and mean pulmonary artery pressures for the HF sensor vs RHC were -4.4 ± 0.3, 2.5 ± 1.0, and -0.8 ± 1.3 mm Hg, respectively. There were no serious device-related adverse events. A postmortem analysis of the HF sensor in a patient who died 12 months after implant demonstrated complete endothelialization and no evidence of thrombosis. CONCLUSIONS This trial supports the safety and accuracy of this pulmonary artery pressure monitoring system in patients with HF and the conduct of randomized trials of implantable hemodynamic monitoring in HF, using this system.

Clinical Characteristics and Outcomes of Intravenous Inotropic Therapy in Advanced Heart Failure

Background—Inotrope use in heart failure treatment was associated with improved symptoms, but worse survival in clinical trials. However, these studies predated use of modern heart failure therapies. This study evaluates contemporary outcomes on long-term inotropes. Methods and Results—We collected baseline and postinotrope data on 197 patients discharged on inotropes between January 2007 and March 2013. Baseline characteristics, hemodynamic and clinical changes on inotropes, and survival were evaluated. Patients initiated on inotropes had refractory heart failure, with median baseline New York Heart Association class IV, cardiac index of 1.7 L/min per m2, pulmonary capillary wedge pressure of 25.6 mm Hg, and left ventricular ejection fraction of 18.7%. Inotropes were used in patients listed for transplant or scheduled for left ventricular assist device (LVAD; 60 patients), in patients being evaluated for LVAD/transplant (20 patients), for stabilization pending cardiac resynchronization therapy/percutaneous coronary intervention (4 patients), in patients who were offered LVAD but chose inotropes (15 patients), and for palliation (98 patients). Milrinone was used in 84.8% and dobutamine in 15.2%. At the end of the study, 68 patients had died, 24 were weaned off inotropes, 23 were transplanted, 32 received LVADs, and 50 remained on inotropes. Patients who received inotropes for palliation or those who preferred inotropes over LVAD had median survival of 9.0 months (interquartile range, 3.1–37.1 months), actuarial 1-year survival of 47.6%, and 2-year survival of 38.4%. Of 60 patients who were placed on inotropes as a bridge to transplant/LVAD, 55 were successfully maintained on inotropes until transplant/LVAD. Conclusions—Survival on inotropes for patients who are not candidates for transplant/LVAD is modestly better than previously reported, but remains poor. Inotropes are effective as a bridge to transplant/LVAD.

Octreotide in the management of recurrent gastrointestinal bleed in patients supported by continuous flow left ventricular assist devices.

Gastrointestinal (GI) bleeding is the most common cause of readmission in patients supported by continuous flow left ventricular assist devices (CF-LVAD). We describe our experience in the off-label use of octreotide in the management of recurrent GI bleed in this population. Of 116 patients implanted with a CF-LVAD at our institution, seven had recurrent GI bleeding unresponsive to conventional management and were started in chronic octreotide injections. Hospitalizations due to GI bleeding, number of packed red blood cells transfused, and number of endoscopic procedures were compared 3 months before and after octreotide treatment. In the overall cohort, there were no differences in these three endpoints. When one patient with differing characteristics was excluded from the analysis there was a trend (p = 0.06) to a reduction of hospitalizations due to GI bleeding, number of blood transfusions, and number of endoscopic procedures. Octreotide exhibit a favorable trend in the frequency of admissions, blood transfusions, and endoscopic procedures in most patients with recurrent GI bleed. Further prospective studies are needed to clarify its benefits in this population.

Beyond survival: Recommendations from INTERMACS for assessing function and quality of life with mechanical circulatory support

From the Division of Cardiac Surgery, Northwestern University, Chicago, Illinois; Cardiovascular Division, Brigham & Women’s Hospital, Boston, Massachusetts; Department of Cardiac Surgery, University of Michigan, Ann Arbor, Michigan; Heart and Vascular Institute, University of Pittsburgh, Pittsburgh, Pennsylvania; Division of Cardiovascular Diseases, University of Alabama at Birmingham, Birmingham, Alabama; Division of Cardiovascular Medicine, University of Louisville, Louisville, Kentucky; Division of Cardiology, Harvard Medical School, Boston, Massachusetts; and the Department of Cardiothoracic Surgery, University of Alabama at Birmingham, Birmingham, Alabama.