Showing papers in "Journal of Heart and Lung Transplantation in 2015"
TL;DR: The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment and a detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented.
Abstract: The seventh annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 9 years of patient enrollment. The Registry includes >15,000 patients from 158 participating hospitals. Trends in device strategy, patient profile at implant and survival are presented. Risk factors for mortality with continuous-flow pumps are updated, and the major causes/modes of death are presented. The adverse event burden is compared between eras, and health-related quality of life is reviewed. A detailed analysis of outcomes after mechanical circulatory support for ambulatory heart failure is presented. Recent summary data from PediMACS and MedaMACS is included. With the current continuous-flow devices, survival at 1 and 2 years is 80% and 70%, respectively.
1,229 citations
Stanford University1, University of Zurich2, Freeman Hospital3, Duke University4, University of Toronto5, Columbia University6, University of Washington7, Washington University in St. Louis8, Alfred Hospital9, Katholieke Universiteit Leuven10, University of Colorado Denver11, St. Vincent's Health System12
TL;DR: Recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation.
Abstract: The appropriate selection of lung transplant recipients is an important determinant of outcomes. This consensus document is an update of the recipient selection guidelines published in 2006. The Pulmonary Council of the International Society for Heart and Lung Transplantation (ISHLT) organized a Writing Committee of international experts to provide consensus opinion regarding the appropriate timing of referral and listing of candidates for lung transplantation. A comprehensive search of the medical literature was conducted with the assistance of a medical librarian. Writing Committee members were assigned specific topics to research and discuss. The Chairs of the Writing Committee were responsible for evaluating the completeness of the literature search, providing editorial support for the manuscript, and organizing group discussions regarding its content. The consensus document makes specific recommendations regarding the timing of referral and of listing for lung transplantation. These recommendations include discussions not present in previous ISHLT guidelines, including lung allocation scores, bridging to transplant with mechanical circulatory and ventilator support, and expanded indications for lung transplantation. In the absence of high-grade evidence to support decision making, these consensus guidelines remain part of a continuum of expert opinion based on available studies and personal experience. Some positions are immutable. Although transplant is rightly a treatment of last resort for end-stage lung disease, early referral allows proper evaluation and thorough patient education. Subsequent waiting list activation implies a tacit agreement that transplant offers a significant individual survival advantage. It is both the challenge and the responsibility of the transplant community globally to ensure organ allocation maximizes the potential benefits of a scarce resource, thereby achieving that advantage.
1,063 citations
TL;DR: This Registry Report focuses on an overall theme of recipient early graft failure, and reports data for donor and recipient characteristics, transplant events, and recipient treatments and outcomes.
Abstract: This section of the 32nd official International Society for Heart and Lung Transplantation (ISHLT) Registry Report of 2015 summarizes data from 51,440 adult lung and 3,820 adult heart-lung transplants that occurred through June 30, 2014. This publication reports data for donor and recipient characteristics, transplant events, and recipient treatments and outcomes. This Registry Report focuses on an overall theme of recipient early graft failure. The Registry’s online full slide set provides more detail, additional analyses, and other information not included in this publication.
503 citations
TL;DR: Data are submitted to the ISHLT Registry by national and multinational organ/data exchange organizations and individual centers.
Abstract: Data are submitted to the ISHLT Registry by national and multinational organ/data exchange organizations and individual centers. Since the Registry’s inception, 418 heart transplant centers, 242 lung transplant centers and 174 heart–lung transplant centers have reported data. The Registry website (www.ishlt.org/registries) provides spread sheets that show data elements collected in the Registry. The online slide set (http://www.ishlt.org/registries/slides.asp? slides=heartLungRegistry) provides POWERPOINT slides of figures and tables that support this study. The site contains additional slides for this report and slide sets from the previous annual reports.
432 citations
TL;DR: In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit, and data support its probable benefit in this gravely ill patient population.
Abstract: Background Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP (Abiomed, Danvers, MA), in a prospective, multicenter trial. Methods Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy. Results The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m 2 ( p p Conclusions In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.
302 citations
TL;DR: The anatomy and physiology of the RV and how it changes in the setting of LVAD support are reviewed and proposed mechanisms and describe biochemical, echocardiographic, and hemodynamic predictors of RVF in LVAD patients are described.
Abstract: Most patients with advanced systolic dysfunction who are assessed for a left ventricular assist device (LVAD) also have some degree of right ventricular (RV) dysfunction. Hence, RV failure (RVF) remains a common complication of LVAD placement. Severe RVF after LVAD implantation is associated with increased peri-operative mortality and length of stay and can lead to coagulopathy, altered drug metabolism, worsening nutritional status, diuretic resistance, and poor quality of life. However, current medical and surgical treatment options for RVF are limited and often result in significant impairments in quality of life. There has been continuing interest in developing risk models for RVF before LVAD implantation. This report reviews the anatomy and physiology of the RV and how it changes in the setting of LVAD support. We will discuss proposed mechanisms and describe biochemical, echocardiographic, and hemodynamic predictors of RVF in LVAD patients. We will describe management strategies for reducing and managing RVF. Finally, we will discuss the increasingly recognized and difficult to manage entity of chronic RVF after LVAD placement and describe opportunities for future research.
301 citations
TL;DR: The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014, which was most apparent during the first 3 months post-implant.
Abstract: Background Pump thrombosis in durable continuous-flow pumps is a barrier to long-term mechanical circulatory support. Earlier Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data identified an increasing risk of pump thrombosis in recent years with the HeartMate II (HMII) left ventricular assist device. The current analysis examines pump thrombosis in the patient cohort extended through June 2014. Methods The INTERMACS identified 9,808 adult patients from 144 institutions receiving a primary HMII implant between April 2008 and June 30, 2014. Pump thrombosis was identified at time of explant, transplant or death. Risk factors for pump thrombosis were examined by multivariable analysis in the hazard function domain. The association between pump thrombosis and implant year was modeled in the hazard domain. Results Parametric hazard modeling of thrombosis by year of implant identified an increasing risk of pump thrombosis from 2009 through 2013, followed by a decrease in the risk during the first half of 2014, which was most apparent during the first 3 months post-implant. Risk factors for pump thrombosis included younger age ( p p = 0.02), history of non-compliance ( p = 0.004), severe right heart failure ( p = 0.02), later date of implant ( p p p Conclusions The small, but progressive increase in the incidence of pump thrombosis observed between 2010 and 2013 with the HMII pump had reversed somewhat in the first half of 2014. Identification of marked elevation of lactate dehydrogenase during the first month offers an opportunity for early intervention strategies.
168 citations
TL;DR: This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors, and the mechanism of donor death within the DCD group seemed to influence recipient early survival.
Abstract: BACKGROUND: The objective of this study was to review the international experience in lung transplantation using lung donation after circulatory death (DCD).METHODS: In this retrospective study, data from the International Society for Heart and Lung Transplantation (ISHLT) DCD Registry were analyzed. The study cohort included DCD lung transplants performed between January 2003 and June 2013, and reported to the ISHLT DCD Registry as of April 2014. The participating institutions included 10 centers in North America, Europe and Australia. The control group was a cohort of lung recipients transplanted using brain-dead donors (DBDs) during the same study period. The primary end-point was survival after lung transplantation.RESULTS: There were 306 transplants performed using DCD donors and 3,992 transplants using DBD donors during the study period. Of the DCD transplants, 94.8% were Maastricht Category whereas 4% were Category IV and 1.2% Category V (euthanasia). Heparin was given in 54% of the cases, donor extubation occurred in 90% of the cases, and normothermic ex vivo lung perfusion (EVLP) was used in 12%. The median time from withdrawal of life support therapy (WLST) to cardiac arrest was 15 minutes (5th to 95th percentiles of 5 to 55 minutes), and from WLST to cold flush was 33 minutes (5th to 95th percentiles of 19.5 to 79.5 minutes). Recipient age and medical diagnosis were similar in DCD and DBD groups (p = not significant ENS]). Median hospital length of stay was 18 days in DCD lung transplants and 16 days in DBD transplants (p = 0.016). Thirty-day survival was 96% in the DCD group and 97% in the DBD group. One-year survival was 89% in the DCD group and 88% in the DBD group (p = NS). Five-year survival was 61% in both groups (p = NS). The mechanism of donor death within the DCD group seemed to influence recipient early survival. The survival rates through 30 days were significantly different by donor mechanism of death (p = 0.0152). There was no significant correlation between the interval of WLST to pulmonary flush with survival (p = 0.11).CONCLUSION: This large study of international, multi-center experience demonstrates excellent survival after lung transplantation using DCD donors. It should be further evaluated whether the mechanism of donor death influences survival after DCD transplant. (C) 2015 International Society for Heart and Lung Transplantation. All rights reserved.
162 citations
TL;DR: A case report of the first implantation of the HeartMate III LVAD to support a patient with severe heart failure, a 55-year-old man with the diagnosis of dilated cardiomyopathy and a recent history of multiple hospital admissions due to worsening heart failure symptoms is presented.
Abstract: Outcomes of heart failure patients supported by a continuous-flow left ventricular assist device (LVAD) have steadily improved during the past decade, largely due to better patient selection and management. Nevertheless, adverse events, such as bleeding, infection, stroke, and thrombus, persist and limit the overall effectiveness of this therapy. Bleeding is the most common serious adverse event that results from the extensive surgery required for implantation and blood component damage due to shear forces in the small blood flow paths of current design axialflow and centrifugal-flow pumps. Excessive bleeding results in reoperations, intensive care time, and total hospital stay, which greatly increases a patient’s exposure for infection. The current clinically used pumps create levels of shear force that can activate platelets and damage von Willebrand factor, causing a disruption in the coagulation system that can manifest as thrombosis or gastrointestinal bleeding. The HeartMate III LVAD (Thoratec Corp, Pleasanton, CA) is a new compact intrapericardial centrifugal-flow pump with a full magnetically levitated rotor (Figure 1). The design differs from currently used devices due to actively controlled rotation and levitation of the rotor allowing gaps in the blood flow that are 10 to 20 times wider, which may minimize blood component trauma and result in more stable coagulation. The HeartMate III is now under clinical investigation, and we present here a case report of the first implantation of the device to support a patient with severe heart failure. The patient is a 55-year-old man with the diagnosis of dilated cardiomyopathy and a recent history of multiple hospital admissions due to worsening heart failure symptoms. With multiple medications, the mean arterial blood pressure was 70 mm Hg, cardiac index was 2.1 liters/min/m, and the left ventricular ejection fraction was 10% to 15%. He was classified as Interagency Registry for Mechanically Assisted Circulatory Support Profile 3. After meeting the HeartMate III Conformite Europeene Mark Study inclusion criteria, the patient gave informed consent, and the implantation was performed by Dr. Schmitto and his team at Hannover Medical School, Hanover, Germany on June 25, 2014. After a median sternotomy, the pericardium was only partially opened to help protect right heart function yet allowing access to the vena cava and aorta for cardiopulmonary bypass cannulation. Once full cardiopulmonary bypass was started, the pericardium was fully opened, the heart was elevated, and the myocardium was cored with the HeartMate coring knife approximately 1 cm medial to the left ventricular apex. The sewing cuff was attached around the apical opening with 2-0 Ethibond pledgeted sutures. The inflow conduit was inserted into the left ventricle, and the device was quickly secured to the heart with a locking mechanism. The outflow graft was trimmed for length and anastomosed to the ascending aorta. The percutaneous lead (driveline) was externalized with a doubletunnel technique and exited through the right upper quadrant of the abdominal wall. Cardiopulmonary bypass lasted 59 minutes, and the total operative time was 149 minutes.
146 citations
TL;DR: Data are submitted to the ISHLT Registry by national and multinational organ/data exchange organizations and individual centers.
Abstract: Data are submitted to the ISHLT Registry by national and multinational organ/data exchange organizations and individual centers. Since the Registry’s inception, 418 heart transplant centers, 242 lung transplant centers and 174 heart–lung transplant centers have reported data. The Registry website (www.ishlt.org/registries) provides spread sheets that show data elements collected in the Registry. The online slide set (http://www.ishlt.org/registries/slides.asp? slides=heartLungRegistry) provides POWERPOINT slides of figures and tables that support this study. The site contains additional slides for this report and slide sets from the previous annual reports.
141 citations
TL;DR: Late RHF is common after continuous-flow LVAD implantation, but does not affect survival during LVAD support, however, it is associated with worse overall outcomes in the bridge-to-transplant (BTT) population.
Abstract: Background Right heart failure (RHF) is an unresolved issue during continuous-flow left ventricular assist device (LVAD) support. Little is known about the incidence and clinical significance of late RHF during LVAD support. Methods Between May 2004 and December 2013, 336 patients underwent continuous-flow LVAD implantation. Of these, 293 patients (87%) discharged with isolated LVAD support were included in this study. Late RHF was defined as HF requiring re-admission and medical or surgical intervention after initial surgery. Results Late RHF occurred in 33 patients (11%) at a median of 99 days after discharge (range 19 to 1,357 days). Freedom from late RHF rates were 87%, 84% and 79% at 1, 2 and 3 years, respectively. RHF recurred in 15 patients. Three patients required right ventricular assist device insertion. Univariable Cox proportional hazards regression model showed diabetes mellitus (HR 2.05, 95% CI 1.03 to 4.06, p = 0.04), body mass index >29 (HR 2.47, 95% CI 1.24 to 4.94, p = 0.01) and blood urea nitrogen level >41 mg/dl (HR 2.19; 95% CI 1.10 to 4.36; p = 0.025) as significant predictors for late RHF. Estimated on-device survival rates at 2 years were 73% in the RHF group and 82% in the non-RHF group ( p = 0.20). However, overall survival at 2 years was significantly worse in patients who developed late RHF (60% vs 85%, p = 0.016). This reduction was mostly attributed to worse overall outcomes in the bridge-to-transplant (BTT) population. Conclusions Late RHF is common after continuous-flow LVAD implantation, but does not affect survival during LVAD support. However, it is associated with worse overall outcomes in the BTT population.
Stanford University1, Duke University2, Boston Children's Hospital3, University of Colorado Boulder4, Cincinnati Children's Hospital Medical Center5, Washington University in St. Louis6, University of Alabama at Birmingham7, University of Pittsburgh8, Medical University of South Carolina9, Children's Hospital of Wisconsin10
TL;DR: There were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population, and the most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection.
Abstract: Background Ventricular assist devices (VADs) have been used in children on an increasing basis in recent years. One-year survival rates are now >80% in multiple reports. In this report we describe adverse events experienced by children with durable ventricular assist devices, using a national-level registry (PediMACS, a component of INTERMACS) Methods PediMACS is a national registry that contains clinical data on patients who are Results This report comprises data from 200 patients with a median age of 11 years (range 11 days to 18 years), and total follow-up of 783 patient-months. The diagnoses were cardiomyopathy ( n = 146, 73%), myocarditis ( n = 17, 9%), congenital heart disease ( n = 35, 18%) and other ( n = 2, 1%). Pulsatile-flow devices were used in 91 patients (45%) and continuous-flow devices in 109 patients (55%). Actuarial survival was 86% at 6 months. There were 418 adverse events reported. The most frequent events were device malfunction ( n = 79), infection ( n = 78), neurologic dysfunction ( n = 52) and bleeding ( n = 68). Together, these accounted for 277 events, 66% of the total. Although 38% of patients had no reported adverse event and 16% of patients had ≥5 adverse events. Adverse events occurred at all time-points after implantation, but were most likely to occur in the first 30 days. For continuous-flow devices, there were broad similarities in adverse event rates between this cohort and historic rates from the INTERMACS population. Conclusions In this study cohort, the overall rate of early adverse events (within 90 days of implantation) was 86.3 events per 100 patient-months, and of late adverse events it was 20.4 events per 100 patient-months. The most common adverse events in recipients of pulsatile VADs were device malfunction, neurologic dysfunction, bleeding and infection. For continuous-flow VADs, the most common adverse events were infection, bleeding, cardiac arrhythmia, neurologic dysfunction and respiratory failure. Compared with an adult INTERMACS cohort, the overall rate and distribution of adverse events appears similar.
TL;DR: Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival, suggesting serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications.
Abstract: Background Data from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) were used previously to develop a risk score calculator to predict 1-year survival. We evaluated prognostic implications of changes in the risk score and individual risk-score parameters over 12 months. Methods Patients were grouped by decreased, unchanged, or increased risk score from enrollment to 12 months. Kaplan-Meier estimates of subsequent 1-year survival were made based on change in the risk score during the initial 12 months of follow-up. Cox regression was used for multivariable analysis. Results Of 2,529 patients in the analysis cohort, the risk score was decreased in 800, unchanged in 959, and increased in 770 at 12 months post-enrollment. Six parameters (functional class, systolic blood pressure, heart rate, 6-minute walk distance, brain natriuretic peptide levels, and pericardial effusion) each changed sufficiently over time to improve or worsen risk scores in ≥5% of patients. One-year survival estimates in the subsequent year were 93.7%, 90.3%, and 84.6% in patients with a decreased, unchanged, and increased risk score at 12 months, respectively. Change in risk score significantly predicted future survival, adjusting for risk at enrollment. Considering follow-up risk concurrently with risk at enrollment, follow-up risk was a much stronger predictor, although risk at enrollment maintained a significant effect on future survival. Conclusions Changes in REVEAL risk scores occur in most patients with pulmonary arterial hypertension over a 12-month period and are predictive of survival. Thus, serial risk score assessments can identify changes in disease trajectory that may warrant treatment modifications.
TL;DR: Survival after LTx from DCD is comparable to survival afterLTx from DBD in observational cohort studies, and DCD appears to be a safe and effective method to expand the donor pool.
Abstract: Background Lung transplantation (LTx) can extend life expectancy and enhance the quality of life for select patients with end-stage lung disease. In the setting of donor lung shortage and waiting list mortality, the interest in donation after cardiocirculatory death (DCD) is increasing. We performed a systematic review and meta-analysis to compare outcomes between DCD and conventional donation after brain death (DBD). Methods PubMed, CINAHL, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Scopus, Web of Science, and ClinicalTrials.gov were searched. We identified original research studies with 1-year post-transplant survival data involving >5 DCD transplants. We performed meta-analyses examining 1-year survival, primary graft dysfunction, and acute rejection after LTx. Results We identified 519 citations; 11 observational cohort studies met our inclusion criteria for systematic review, and 6 met our inclusion criteria for meta-analysis. There were no differences found in 1-year mortality after LTx between DCD and DBD cohorts in individual studies or in the meta-analysis (DCD [ n = 271] vs DBD [ n = 2,369], relative risk [RR] 0.88, 95% confidence interval [CI] 0.59–1.31, p = 0.52, I 2 = 0%). There was also no difference between DCD and DBD in a pooled analysis of 5 studies reporting on primary graft dysfunction (RR 1.09, 95% CI 0.68–1.73, p = 0.7, I 2 = 0%) and 4 studies reporting on acute rejection (RR 0.72, 95% CI 0.49–1.05, p = 0.09, I 2 = 0%). Conclusions Survival after LTx from DCD is comparable to survival after LTx from DBD in observational cohort studies. DCD appears to be a safe and effective method to expand the donor pool.
TL;DR: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure.
Abstract: BACKGROUND: Mutations in the telomerase complex (TERT and TR) are associated with pulmonary fibrosis and frequent hematologic manifestations. The aim of this study was to characterize the prognosis of lung transplantation in patients with TERT or TR mutations. METHODS: Patients with documented TERT or TR mutations who received a lung transplant between 2007 and 2013 in France were identified via an exhaustive search of the lung transplantation network, one expert genetic laboratory, and the clinical research network on rare pulmonary diseases. RESULTS: There were 9 patients (7 men) with TERT (n = 6) or TR (n = 3) mutations who received a single (n = 8) or a double (n = 1) lung transplant for pulmonary fibrosis. Median age was 50 years (range, 35-61 years) at diagnosis and 52 years (range, 37-62 years) at the time of lung transplantation. Thrombocytopenia was present in 7 patients before lung transplantation. After lung transplantation, 6 patients developed myelodysplasia and/or bone marrow failure, directly contributing to death in 4 cases. Anemia was observed in 9 patients, and neutropenia was observed in 3 patients. The median survival after lung transplantation was 214 days (range, 59-1,709 days). CONCLUSIONS: Patients with mutations of the telomerase complex are at high risk of severe hematologic complications after lung transplantation, in particular, bone marrow failure. Specific recommendations should be developed for appropriate guidance regarding hematologic risk assessment before transplantation and management of the post-transplantation immunosuppressive regimen.
TL;DR: Evaluated ex vivo lung perfusion is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.
Abstract: Background Ex vivo lung perfusion (EVLP) is an effective method to assess and improve the function of otherwise unacceptable lungs, alleviating the shortage of donor lungs. The early results with EVLP have been encouraging, but longer-term results, including functional and patient-reported outcomes, are not well characterized. Methods This retrospective single-center study included all lung transplants performed between September 2008 and December 2012. We investigated whether survival or rate of chronic lung allograft dysfunction (CLAD) differed in recipients of EVLP-treated lungs compared with contemporaneous recipients of conventional donor lungs. We also studied functional (highest forced expiratory volume in 1 second predicted, change in 6-minute walk distance, number of acute rejection episodes) and quality of life outcomes. Results Of 403 lung transplants that were performed, 63 patients (15.6%) received EVLP-treated allografts. Allograft survival for EVLP and conventional donor lung recipients was 79% vs 85%, 71% vs 73%, and 58% vs 57% at 1, 3, and 5 years after transplant, respectively (log-rank p = not significant). Freedom from CLAD was also similar (log-rank p = 0.53). There were no significant differences in functional outcomes such as highest forced expiratory volume in 1 second predicted (76.5% ± 23.8% vs 75.8% ± 22.8%, p = 0.85), change in 6-minute walk distance (194 ± 108 meters vs 183 ± 126 meters, p = 0.57), or the number of acute rejection episodes (1.5 ± 1.4 vs 1.3 ± 1.3, p = 0.36). The EVLP and conventional donor groups both reported a significantly improved quality of life after transplantation, but there was no intergroup difference. Conclusion EVLP is a safe and effective method of assessing and using high-risk donor lungs before transplantation and leads to acceptable long-term survival, graft function, and improvements of quality of life that are comparable with conventionally selected donor lungs.
TL;DR: One-year survival estimates were higher for patients with a baseline 6MWD above vs below a threshold, although no specific threshold was more prognostic than another, and no 6 MWD improvement threshold carries particular prognostic value.
Abstract: Background Clinical studies of pulmonary arterial hypertension have used the change in the 6-minute walk distance (6MWD) as a clinical end point; however, its association with survival outcomes has not been well established. In this analysis, we examined the prognostic value of the baseline 6MWD, absolute thresholds of the 6MWD, and change in the 6MWD. Methods Patients in the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL) with 6MWD at enrollment, with or without a follow-up assessment within the first year of observation, were included. Kaplan-Meier survival estimates were computed for sub-sets with baseline 6MWD results that were above or below all possible thresholds and for sub-sets with a change in the 6MWD that was 10 percentage points above or below all possible thresholds, including improvement thresholds and worsening thresholds. Multivariable Cox regression models assessed the effect of improvement and worsening in the 6MWD on 1-year survival, adjusted for baseline factors. Results One-year survival estimates were higher for patients with a baseline 6MWD above vs below a threshold, although no specific threshold was more prognostic than another. In a model adjusted for the baseline 6MWD and risk score, worsening of the 6MWD over time significantly predicted decreased survival, but improvement in the 6MWD did not affect survival. Conclusions No 6MWD improvement threshold carries particular prognostic value. Improvement in the 6MWD was not associated with survival, but worsening of the 6MWD was strongly and significantly associated with poor prognosis.
Houston Methodist Hospital1, Columbia University2, Hannover Medical School3, Yonsei University4, Mayo Clinic5, Tohoku University6, University of Bologna7, Johns Hopkins University8, University of Cambridge9, Golden Jubilee National Hospital10, University of Regensburg11, Duke University12, University of Texas at Dallas13, Sapienza University of Rome14, Novartis15, University of Giessen16
TL;DR: In this paper, the authors evaluated the safety and efficacy of imatinib in a controlled trial (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy Study [IMPRES]), among pulmonary arterial hypertension patients inadequately responsive to 2 to 3 PAH-specific therapies.
Abstract: Background Imatinib is an oral inhibitor of several protein kinases implicated in the pathophysiology of pulmonary hypertension. Treatment with imatinib resulted in improved hemodynamics and exercise capacity in a controlled trial (Imatinib [QTI571] in Pulmonary Arterial Hypertension, a Randomized Efficacy Study [IMPRES]), among pulmonary arterial hypertension (PAH) patients inadequately responsive to 2 to 3 PAH-specific therapies. Methods The long-term (up to 204 weeks) safety and efficacy of imatinib in this open-label extension study were reviewed until early study termination on April 16, 2014. Of 202 IMPRES-enrolled patients, 66 imatinib and 78 placebo recipients entered the extension. Results Overall, 93.8% (135 of 144) of patients discontinued the extension study; administrative issues (i.e., sponsor termination; 32.6%) and adverse events (31.3%) were the primary reasons for discontinuation. Nine patients completed the extension study before it was terminated. Serious and unexpected adverse events were frequent. These included 6 subdural hematomas in the extension study and 17 deaths during or within 30 days of study end. Although the patients who tolerated imatinib and remained in the extension for a longer duration did experience an improvement in functional class and walk distance, most discontinued the drug and the study. Conclusions Severe adverse events, significant side effects, and a high discontinuation rate limit the utility of imatinib in the treatment of PAH. These risks outweigh any possible improvements in hemodynamics and walk distance seen in those patients able to remain on drug. The off-label use of this compound in PAH is discouraged.
TL;DR: AV closure was associated with increased mortality when compared with repair or replacement in patients with existing aortic insufficiency who underwent LVAD insertion, and the reasons for this association require further investigation.
Abstract: Background Management of existing aortic insufficiency (AI) and mechanical aortic valves in patients undergoing left ventricular assist device (LVAD) implantation remains controversial. Surgical options to address these issues include closure, repair or replacement of the valve. Methods Continuous-flow LVAD/biventricular VAD patients entered into the INTERMACS database between June 2006 and December 2012 were included ( n = 5,344) in this analysis. Outcomes were compared between patients who underwent aortic valve (AV) closure ( n = 125), repair ( n = 95) and replacement ( n = 85). Results Among patients who underwent an AV procedure, actuarial survival was significantly reduced for AV closures (63.2%) compared with AV repairs (76.8%) and replacements (71.8%) ( p = 0.0003). Differences were greater between groups when only INTERMACS Level 1 or 2 patients were analyzed ( p = 0.003). After multivariate adjustment, AV closure remained a significant risk factor for mortality (hazard ratio=1.87, 95% confidence interval 1.39 to 2.53, p p Conclusions AV closure was associated with increased mortality when compared with repair or replacement in patients with AI who underwent LVAD insertion. The reasons for this association require further investigation. This is the largest study to date to examine concomitant AV procedures in patients undergoing LVAD insertion.
TL;DR: Current schemes for post-LVAD RVF risk prediction perform only modestly when applied to external populations, and the Kormos model performed best with this definition.
Abstract: Background Several clinical prediction schemes for right ventricular failure (RVF) risk after left ventricular assist device (LVAD) implantation have been developed in both the pulsatile- and continuous-flow LVAD eras. The performance of these models has not been evaluated systematically in a continuous-flow LVAD cohort. Methods We evaluated 6 clinical RVF prediction models (Michigan, Penn, Utah, Kormos et al, CRITT, Pittsburgh Decision Tree) in 116 patients (age 51 ± 13 years; 41.4% white and 56.0% black; 66.4% men; 56.0% bridge to transplant, 37.1% destination therapy, 17.4% bridge to decision) who received a continuous-flow LVAD (HeartMate II: 79 patients, HeartWare: 37 patients) between 2008 and 2013. Results Overall, 37 patients (31.9%) developed RVF, defined: as pulmonary vasodilator use for ≥48 hours or inotrope use for ≥14 days post-operatively; re-institution of inotropes; multi-organ failure due to RVF; or need for mechanical RV support. Median (Quartile 1 to Quartile 3) time to initial discontinuation of inotropes was 6 (range 4 to 8) days. Among scores, the Michigan score reached significance for RVF prediction but discrimination was modest (C = 0.62 [95% CI 0.52 to 0.72], p = 0.021; positive predictive value [PPV] 60.0%; negative predictive value [NPV] 75.8%), followed by CRITT (C = 0.60 [95% CI 0.50 to 0.71], p = 0.059; PPV 40.5%; NPV 72.2%). Other models did not significantly discriminate RVF. The newer, INTERMACS 3.0 definition for RVF, which includes inotropic support beyond 7 days, was reached by 57 patients (49.1%). The Kormos model performed best with this definition (C = 0.62 [95% CI 0.54 to 0.71], p = 0.005; PPV 64.3%; NPV 59.5%), followed by Penn (C = 0.61), Michigan (C = 0.60) and CRITT (C = 0.60), but overall score performance was modest. Conclusion Current schemes for post-LVAD RVF risk prediction perform only modestly when applied to external populations.
TL;DR: To design interventions to improve functional capacity in patients treated with modern durable LVADs, a detailed understanding of exercise physiology in a continuous-flow circulatory system is necessary.
Abstract: After implantation of a continuous-flow left ventricular assist device (CF-LVAD), exercise capacity in heart failure patients remains reduced with peak oxygen uptake (peak VO2) values averaging from 11 to 20 ml/kg/min. Total cardiac output in CF-LVAD patients during exercise is predominantly determined by pump speed, the pressure difference across the pump, and in some cases ejection through the aortic valve. Fixed pump speed utilized in CF-LVADs may provide insufficient support, resulting in a moderate cardiac output increase during increased physical strain. Ongoing studies are evaluating whether pump speed changes in response to varied loading conditions may enable LVADs to provide sufficient support even during strenuous exercise. In the currently used devices, evidence suggests that focus on optimizing non-cardiac peripheral parameters is vital. Extra-cardiac potentially reversible factors are anemia with low oxygen-carrying capacity, obesity and general deconditioning with low muscle mass. In addition, exercise training in CF-LVAD patients can improve peak VO2. To design interventions to improve functional capacity in patients treated with modern durable LVADs, a detailed understanding of exercise physiology in a continuous-flow circulatory system is necessary. In this review we address the different components of exercise physiology in LVAD patients and point out potential solutions or areas of future research.
TL;DR: A unique pattern of adverse pulmonary vascular remodeling in patients with a long-standing Fontan circulation who had died during follow-up is observed, suggesting that this remodeling pattern may play a major role in long-term attrition of theFontan circulation.
Abstract: Background The Fontan circulation is a palliation for patients with a functionally univentricular heart. It is characterized by gradual attrition over time. An increase in pulmonary vascular resistance could be a key factor in the long-term failure of the Fontan circulation. In this study we aimed to identify pulmonary vascular remodeling in patients with a Fontan circulation. Methods Pulmonary vascular histomorphometric analysis and immunohistochemistry were performed in lung tissue obtained at autopsy from 12 Fontan patients. These patients had died either peri-operatively (Group A: death during or n = 5) or in mid to long-term follow-up (Group B: death >5 years after Fontan completion; n = 7). Two age-matched control groups ( n = 10 and n = 14, respectively) were included. Results Intra-acinar pulmonary vessels in the Fontan Group B patients showed decreased medial thickness ( p = 0.028) compared with age-matched controls, whereas intimal thickness was increased ( p = 0.002). Intimal thickness in the Fontan Group B patients correlated with age at death ( r = 0.964, p r = 0.714, p = 0.036). Immunohistochemistry revealed a reduction of vascular smooth muscles cells in the medial layer of the intra-acinar pulmonary vessels. The eccentric intimal thickening was composed of mainly acellular fibrosis with collagen deposition. Conclusions We observed a unique pattern of adverse pulmonary vascular remodeling in patients with a long-standing Fontan circulation who had died during follow-up. This remodeling pattern may play a major role in long-term attrition of the Fontan circulation.
TL;DR: After lung transplantation, 5-year survival in Canadians with CF is 67%, and 50% of patients live >10 years, despite these impressive probabilities, age at transplant, pancreatic sufficiency and B cepacia infection remain important determinants of survival after lung transplation.
Abstract: BACKGROUND: Contemporary studies evaluating post-transplant survival are limited and often include data from single centers or selected sub-groups. The purpose of this study was to evaluate overall transplant survival and to identify risk factors associated with death after transplant. METHODS: The Canadian Cystic Fibrosis Registry, a population-based cohort, was used to describe survival after lung transplant. Pre-transplant factors associated with post-transplant survival were estimated using Cox proportional hazards models. RESULTS: Between 1988 and 2012, 580 patients received a lung transplant. In the entire cohort, post– lung transplant 1-year survival was 87.8%, 5-year survival was 66.7%, and 10-year survival was 50.2%. Median post-transplant survival was 3.3 years (95% confidence interval [CI] ¼ 2.13–6.56) in patients infected with Burkholderia cepacia complex compared with 12.36 years (95% CI ¼ 10.34–17.96) in patients without B cepacia infection (hazard ratio [HR] ¼ 2.63, 95% CI ¼ 2.0–3.44). After adjustment, there was a non-significant trend toward better post-transplant survival with increasing year of transplant (HR ¼ 0.98, 95% CI ¼ 0.96–1.00). Pancreatic sufficiency (HR ¼ 2.13, 95% CI ¼ 1.41–3.20) and age at transplant such that youngest and oldest had the poorest survival (p o 0.001) were significant negative predictors of survival. The risk of death after transplant for patients infected with B cepacia was highest within the first year (HR ¼ 6.29, 95% CI ¼ 3.87–10.21) but remained elevated 41 year after transplant (HR ¼ 1.92, 95% CI ¼ 1.33–2.77) compared with patients without B cepacia infection. CONCLUSIONS: After lung transplantation, 5-year survival in Canadians with CF is 67%, and 50% of patients live 410 years. Despite these impressive probabilities, age at transplant, pancreatic sufficiency and B cepacia infection remain important determinants of survival after lung transplantation. J Heart Lung Transplant 2015;34:1139–1145 r 2015 International Society for Heart and Lung Transplantation. All rights reserved.
TL;DR: Prognosis after late AMR is poor despite aggressive immunosuppressive therapies, and Fulminant CAV is a common condition in patients with proven and treated late acute AMR.
Abstract: Background Late antibody-mediated rejection (AMR) after heart transplantation is suspected to be associated with a poor short-term prognosis. Methods A retrospective single-center observational study was performed. Late AMR was defined as AMR occurring at least 1 year after heart transplantation. The study included all consecutive patients with proven and treated late acute AMR at the authorsʼ institution between November 2006 and February 2013. The aim was to analyze the prognosis after late AMR, including mortality, recurrence of AMR, left ventricular ejection fraction, and cardiac allograft vasculopathy (CAV). Selected endomyocardial biopsy specimens obtained before AMR were also blindly reviewed to identify early histologic signs of AMR. Results The study included 20 patients treated for late AMR. Despite aggressive immunosuppressive therapies (100% of patients received intravenous methylprednisolone, 90% received intravenous immunoglobulin [IVIg],85% received plasmapheresis, 45% received rituximab), the prognosis remained poor. Survival after late AMR was 80% at 1 month, 60% at 3 months, and 50% at 1 year. All early deaths ( n = 8) were directly attributable to graft dysfunction or to complication of the intense immunosuppressive regimen. Among survivors at 3 months ( n = 12), histologic persistence or recurrence of AMR, persistent left ventricular dysfunction, and fulminant CAV were common (33%, 33%, and 17% of patients). Microvascular inflammation was detected in at least 1 biopsy specimen obtained before AMR in 13 patients (65%). Conclusions Prognosis after late AMR is poor despite aggressive immunosuppressive therapies. Fulminant CAV is a common condition in these patients. Microvascular inflammation is frequent in endomyocardial biopsy specimens before manifestation of symptomatic AMR.
TL;DR: From the Department of Cardiology, St. Vincent Heart Center of Indiana, Indianapolis, Indiana; Division of Cardiac Surgery, Peter Munk Cardiac Centre, Toronto, Ontario, Canada; Department of Surgery, University of Rochester, Rochester, New York; and the department of cardiology, Houston Methodist Hospital, Houston, Texas.
Abstract: From the Department of Cardiology, St. Vincent Heart Center of Indiana, Indianapolis, Indiana; Division of Cardiac Surgery, Peter Munk Cardiac Centre, Toronto, Ontario, Canada; Department of Surgery, University of Rochester, Rochester, New York; Department of Cardiothoracic Surgery, Abbott Northwestern Hospital, Minneapolis, Minnesota; Bioengineering Program, San Diego State University, San Diego, California; Division of Cardiology, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, New York; and the Department of Cardiology, Houston Methodist Hospital, Houston, Texas.
TL;DR: A fibrin scaffold loaded with ESC-derived cardiac progenitors resulted in sustained improvement in contractility and attenuation of remodeling without sustained donor cell engraftment.
Abstract: BACKGROUND: Cardiac-committed cells and biomimetic scaffolds independently improve the therapeutic efficacy of stem cells. In this study we tested the long-term effects of their combination.
METHODS: Eighty immune-deficient rats underwent permanent coronary artery ligation. Five to 7 weeks later, those with an echocardiographically measured ejection fraction (EF) ≤55% were re-operated on and randomly allocated to receive a cell-free fibrin patch (n = 25), a fibrin patch loaded with 700,000 human embryonic stem cells (ESC) pre-treated to promote early cardiac differentiation (SSEA-1+ progenitors [n = 30]), or to serve as sham-operated animals (n = 25). Left ventricular function was assessed by echocardiography at baseline and every month thereafter until 4 months. Hearts were then processed for assessment of fibrosis and angiogenesis and a 5-component heart failure score was constructed by integrating the absolute change in left ventricular end-systolic volume (LVESV) between 4 months and baseline, and the quantitative polymerase chain reaction (qPCR)-based expression of natriuretic peptides A and B, myosin heavy chain 7 and periostin. All data were recorded and analyzed in a blinded manner.
RESULTS: The cell-treated group consistently yielded better functional outcomes than the sham-operated group (p = 0.002 for EF; p = 0.01 for LVESV). Angiogenesis in the border zone was also significantly greater in the cell-fibrin group (p = 0.006), which yielded the lowest heart failure score (p = 0.04 vs sham). Engrafted progenitors were only detected shortly after transplantation; no grafted cells were identified after 4 months. There was no teratoma identified.
CONCLUSIONS: A fibrin scaffold loaded with ESC-derived cardiac progenitors resulted in sustained improvement in contractility and attenuation of remodeling without sustained donor cell engraftment. A paracrine effect, possibly on innate reparative responses, is a possible mechanism for this enduring effect.
TL;DR: Reducing anti-thrombotic therapies in response to bleeding among HMII patients was achievable but may be associated with a higher risk for device thrombosis.
Abstract: Background Patients with bleeding complications during left ventricular assist device (LVAD) support often require a reduction in the recommended warfarin plus aspirin regimen. To characterize those who can be safely managed with a reduced anti-thrombotic strategy, the TRACE (STudy of Reduced Anti-Coagulation/Anti-platelEt Therapy in Patients with the HeartMate II LVAS) study was initiated in the United States (U.S.) and Europe. Methods The TRACE U.S. arm enrolled HeartMate II (HMII; Thoratec) outpatients on a regimen of reduced anti-thrombotic therapy (RT), defined as vitamin K antagonist (warfarin) only, aspirin only, or no anti-thrombotic agent. The indication for RT, changes in anti-thrombotic therapies, and patient outcomes after RT were documented. Results for patients reaching 12 months or outcome are presented here. Results Between April 2012 and June 2013, 100 HMII outpatients (85% men) on RT (median age 64.5 [interquartile range, 32, 82] years, 61% with ischemic etiology, 69% destination therapy) were enrolled from 9 U.S. sites. The primary reason for RT initiation was in response to a bleeding event (82%). Pharmacotherapy at RT initiation included warfarin only (38%), aspirin only (28%), or no anti-thrombotic agent (34%). Freedom from ischemic stroke at 1 year was 93.8% ± 2.5%, and freedom from device thrombosis was 92.7% ± 2.7%. Despite RT, a subsequent bleeding event occurred in 52%. Conclusions Reducing anti-thrombotic therapies in response to bleeding among HMII patients was achievable but may be associated with a higher risk for device thrombosis. Furthermore, despite an RT strategy, bleeding often will persist in those prone to such events.
TL;DR: Standardized angiographic criteria show CMV infection is associated with the development of CAV, and these patients died because of it.
Abstract: Background Cardiac allograft vasculopathy ( CAV) is a major cause of long-term morbidity and mortality after heart transplantation (HTx), whose relationship with CMV infection is uncertain. This study evaluated the influence of CMV infection in the development of CAV. Methods We enrolled 166 consecutive HTx recipients who underwent their first transplant from January 1995 to July 2002. All patients received 14 days of intravenous ganciclovir and were prospectively monitored for CMV infection during the first year after HTx. CAV was diagnosed by coronary angiography performed at 1, 5, and 10 years after HTx, following the new criteria of the International Society for Heart and Lung Transplantation. We collected all variables potentially related with the development of CAV. Risk factors were studied using a complementary log-log model. Results After a median follow-up of 11 years (range, 1–17 years), 72 patients (43%) developed CAV (63.8% CAV 1 , 15.2% CAV 2 , 20.8% CAV 3 ). Symptoms secondary to CAV were present in 32% of these patients, and 8% died because of it. In the regression multivariate analysis, independent variables associated with the development of CAV were donor age (hazard ratio [HR], 1.028; 95% confidence interval [CI], 1.002–1.053; p p p p Conclusions Standardized angiographic criteria show CMV infection is associated with the development of CAV.
TL;DR: The potential for recovery of native LV function after long-term continuous-flow LVAD support should encourage a more aggressive approach to ventricular reconditioning with the goal of device explantation and a return to medical management, particularly in young patients with dilated cardiomyopathy.
Abstract: Background The potential for myocardial reconditioning and device explantation after long-term continuous-flow left ventricular assist device (LVAD) support presents an opportunity to delay or avoid transplantation in select patients. Methods Thirty of 657 patients with end-stage heart failure supported with continuous-flow LVADs were assessed for device explantation. Each patient underwent an individualized process of weaning focused on principles of ventricular unloading, gradual reconditioning, and transition to medical therapy. Results After varying reconditioning periods, 27 patients (16 men, 11 women; age, 39 ± 12 years) underwent LVAD explant, and 3 patients (2 men, 1 woman; age, 22 ± 6 years) were evaluated for explantation but could not be weaned. The duration of LVAD support was 533 ± 424 days (range, 42–1,937 days) for the explant cohort and 1,097 ± 424 days (range, 643–1,483) for the non-explant cohort. The LV end-diastolic dimension, LV ejection fraction, systolic pulmonary artery pressure, cardiac output, and cardiac index in the explant cohort were significantly improved at explantation (all, p Conclusions The potential for recovery of native LV function after long-term continuous-flow LVAD support should encourage a more aggressive approach to ventricular reconditioning with the goal of device explantation and a return to medical management, particularly in young patients with dilated cardiomyopathy.
TL;DR: Individuals with Fontan physiology have a high prevalence of hepatic fibrosis, and signs and symptoms of liver disease did not predict histopathologic findings, and few risk factors for advanced disease were identified.
Abstract: Background The Fontan operation redirects venous blood flow directly to the pulmonary circulation in subjects with single ventricle anatomy. Congestive hepatopathy and cirrhosis have been described in subjects with Fontan circulation, but the prevalence of and predictors for liver disease remain unknown. Methods We performed a retrospective study of liver histopathology in Fontan subjects who had liver biopsy or autopsy. All specimens were graded using a pre-determined protocol. Additional data were collected through chart review. Among 68 subjects, specimens were obtained at a median age of 23.2 years (range 5.0 to 52.7 years). Median time since Fontan was 18.1 years (range 1.2 to 32.7 years). Results Centrilobular fibrosis was seen in every specimen, with 41.2% showing Grade 4 centrilobular fibrosis. Portal fibrosis was seen in 82.3% of specimens, with 14.7% showing cirrhosis. Megamitochondria were seen in 58.8% of specimens. Centrilobular fibrosis grade was greater in those with a dominant left or right ventricle than in those with a combined right and left systemic ventricle (p = 0.008). Portal fibrosis grade correlated with alkaline phosphatase (p = 0.04) and mode of biopsy (p = 0.02). Neither centrilobular fibrosis nor portal fibrosis grade was predictive of transplant-free survival or overall survival. Conclusions Individuals with Fontan physiology have a high prevalence of hepatic fibrosis. Signs and symptoms of liver disease did not predict histopathologic findings. Few risk factors for advanced disease were identified. Histopathology findings did not predict transplant-free survival. The role of liver biopsy in this population remains uncertain.