David C. Naftel

Seventh INTERMACS annual report: 15,000 patients and counting

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.

Sixth INTERMACS annual report: a 10,000-patient database.

The sixth annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes the first 8 years of patient enrollment. The analysis is based on data from >10,000 patients and updates demographics, survival, adverse events and risk factors. Among patients with continuous-flow pumps, actuarial survival continues to be 80% at 1 year and 70% at 2 years. The report features a comparison of two eras of continuous-flow durable devices in the USA in terms of device strategy, patient profiles, adverse event burden, survival and quality of life.

Fifth INTERMACS annual report: Risk factor analysis from more than 6,000 mechanical circulatory support patients

The 5th annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 6 years of patient and data collection. The current analysis includes more than 6000 patients and updated risk factors for continuous flow pumps. Among continuous flow pumps, actuarial survival is 80% at 1 year and 70% at 2 years. Quality of life indicators are generally favorable and adverse event burden will likely influence patient selections of advanced heart failure therapies.

Replacement of the Aortic Root in Patients with Marfan's Syndrome

BACKGROUND Replacement of the aortic root with a prosthetic graft and valve in patients with Marfans syndrome may prevent premature death from rupture of an aneurysm or aortic dissection. We reviewed the results of this surgical procedure at 10 experienced surgical centers. METHODS A total of 675 patients with Marfans syndrome underwent replacement of the aortic root. Survival and morbidity-free survival curves were calculated, and risk factors were determined from a multivariable regression analysis. RESULTS The 30-day mortality rate was 1.5 percent among the 455 patients who underwent elective repair, 2.6 percent among the 117 patients who underwent urgent repair (within 7 days after a surgical consultation), and 11.7 percent among the 103 patients who underwent emergency repair (within 24 hours after a surgical consultation). Of the 675 patients, 202 (30 percent) had aortic dissection involving the ascending aorta. Forty-six percent of the 158 adult patients with aortic dissection and a documented aortic diameter had an aneurysm with a diameter of 6.5 cm or less. There were 114 late deaths (more than 30 days after surgery); dissection or rupture of the residual aorta (22 patients) and arrhythmia (21 patients) were the principal causes of late death. The risk of death was greatest within the first 60 days after surgery, then rapidly decreased to a constant level by the end of the first year. CONCLUSIONS Elective aortic-root replacement has a low operative mortality. In contrast, emergency repair, usually for acute aortic dissection, is associated with a much higher early mortality. Because nearly half the adult patients with aortic dissection had an aortic-root diameter of 6.5 cm or less at the time of operation, it may be prudent to undertake prophylactic repair of aortic aneurysms in patients with Marfans syndrome when the diameter of the aorta is well below that size.

The Decomposition of Time-Varying Hazard into Phases, Each Incorporating a Separate Stream of Concomitant Information

Abstract The hazard function of time-related events, such as death or reoperation following heart valve replacement, often is time-varying in a structured fashion, as is the influence of risk factors associated with the events. A completely parametric system is presented for the decomposition of time-varying patterns of risk into additive, overlapping phases, descriptively labeled as early, constant-hazard, and late. Each phase is shaped by a different generic function of time constituting a family of nested equations and is scaled by a separate logit-linear or log-linear function of concomitant information. Model building uses maximum likelihood estimation. The resulting parametric equations permit hazard function, survivorship function, and probability estimates and their confidence limits to be portrayed and adjusted for concomitant information. These provide a comprehensive analysis of time-related events from which inferences may be drawn to improve, for example, the management of patients with valva...

Second INTERMACS annual report: more than 1,000 primary left ventricular assist device implants.

The Interagency Registry For Mechanical Circulatory Support (INTERMACS)1 an NHLBI-sponsored collaboration between the National Heart, Lung, and Blood Institute (NHLBI), the Food and Drug Administration (FDA), the Center for Medicaid and Medicare Services (CMS), and the advanced heart failure/mechanical circulatory support professional community, began prospective patient enrollment and data collection on June 23, 2006. On 3/27/09, CMS mandated that all United States hospitals approved for mechanical circulatory support as Destination Therapy (DT) must enter mechanical circulatory support patient data into a national database, INTERMACS. The power of INTERMACS data stems from the mandatory data submission on all durable mechanical circulatory devices, a formal process for adverse event adjudication, dedicated innovative electronic data submission, data element design to create a template for comparison with medical therapy, rigorous data monitoring, hospital auditing through the United Network of Organ Sharing, and a formal process for data access and publications. Since the inception of INTERMACS, an ongoing evolution of both strategies for device application and the types of available devices has continued to refine the landscape of mechanical circulatory support. Throughout this experience, the only device approved in the United States for permanent “destination” therapy was the HeartMate XVE2, a pulsatile ventricular assist device which is now known to frequently develop bearing wear and require device replacement within 2 years of implantation. Yet, in many countries outside the United States, newer axial flow and centrifugal flow rotary pumps provide chronic circulatory support. INTERMACS only collects data on devices which are FDA-approved for clinical use, and no adult rotary pump was approved in the United States for the first several years of the INTERMACS experience. The spectrum of devices entered into INTERMACS must also be viewed in the context of multiple concurrent U.S. clinical trials of continuous flow pumps implanted as bridge-to-transplant therapy as well as permanent support. Thus, for the first 2 years, despite the rigorous requirements for data completeness and accuracy, INTERMACS suffered from its inability to collect data on newer, more promising rotary pumps which were not yet FDA approved. The INTERMACS playing field changed dramatically in April of 2008, when the HeartMate II axial flow pump received FDA approval for clinical use as bridge-to-transplant therapy in the United States. A portion of this report will examine the changing practice patterns in the application of device type (continuous flow vs. pulsatile) and device strategies over the past three years. In fact, the genesis of INTERMACS, partly by chance and partly by design, uniquely positioned this database to observe, record, and analyze this historical transition (at least for the immediate future) from larger, powerful pulsatile pumps to the world of continuous flow technology, with the unproven promise of greater durability while retaining long-term patient functionality. This report begins the process of long-term evaluation of continuous flow technology against the background of a large registry of detailed patient and device data based on pulsatile pump technology.

The Fourth INTERMACS Annual Report: 4,000 implants and counting

The Fourth Annual Report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) summarizes and analyzes the first 5 years of patient and data collection. With more than 4,000 patients entered into the database, the evolution of pump technology, strategy at implant, and pre-implant patient profiles are chronicled. A risk factor analysis of the entire adult primary implant population is provided, and the recent composition of patient profiles is examined. Current actuarial survival with continuous-flow pumps exceeds 80% at 1 year and 70% at 2 years.

Prospective Trial of a Pediatric Ventricular Assist Device

BACKGROUND Options for mechanical circulatory support as a bridge to heart transplantation in children with severe heart failure are limited. METHODS We conducted a prospective, single-group trial of a ventricular assist device designed specifically for children as a bridge to heart transplantation. Patients 16 years of age or younger were divided into two cohorts according to body-surface area (cohort 1, <0.7 m(2); cohort 2, 0.7 to <1.5 m(2)), with 24 patients in each group. Survival in the two cohorts receiving mechanical support (with data censored at the time of transplantation or weaning from the device owing to recovery) was compared with survival in two propensity-score-matched historical control groups (one for each cohort) undergoing extracorporeal membrane oxygenation (ECMO). RESULTS For participants in cohort 1, the median survival time had not been reached at 174 days, whereas in the matched ECMO group, the median survival was 13 days (P<0.001 by the log-rank test). For participants in cohort 2 and the matched ECMO group, the median survival was 144 days and 10 days, respectively (P<0.001 by the log-rank test). Serious adverse events in cohort 1 and cohort 2 included major bleeding (in 42% and 50% of patients, respectively), infection (in 63% and 50%), and stroke (in 29% and 29%). CONCLUSIONS Our trial showed that survival rates were significantly higher with the ventricular assist device than with ECMO. Serious adverse events, including infection, stroke, and bleeding, occurred in a majority of study participants. (Funded by Berlin Heart and the Food and Drug Administration Office of Orphan Product Development; ClinicalTrials.gov number, NCT00583661.).

Third INTERMACS Annual Report: The evolution of destination therapy in the United States

The third annual report of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) provides documentation of the current landscape of durable mechanical circulatory support in the United States. With nearly 3,000 patients entered into the database, the transition to continuous-flow pump technology is evident and dramatic. This report focuses on the rapidly expanding experience with mechanical circulatory support as destination therapy. The current 1-year survival of 75% with continuous-flow destination therapy provides a benchmark for the evolving application of this therapy.

Outcomes of Children Bridged to Heart Transplantation With Ventricular Assist Devices A Multi-Institutional Study

Background— Current ventricular assist devices (VADs) in the United States are designed primarily for adult use. Data on VADs as a bridge to transplantation in children are limited. Methods and Results— A multi-institutional, prospectively maintained database of outcomes in children after listing for heart transplantation (n=2375) was used to analyze outcomes of VAD patients (n=99, 4%) listed between January 1993 and December 2003. Median age at VAD implantation was 13.3 years (range, 2 days to 17.9 years); diagnoses were cardiomyopathy (78%) and congenital heart disease (22%). Mean duration of support was 57 days (range, 1 to 465 days). Seventy-three percent were supported with a long-term device, with 39% requiring biventricular support. Seventy-seven patients (77%) survived to transplantation, 5 patients were successfully weaned from support and recovered, and 17 patients (17%) died on support. In the recent era (2000 to 2003), successful bridge to transplantation with VAD was achieved in 86% of patients. Peak hazard for death while waiting was the first 2 weeks after VAD placement. Risk factors for death while awaiting a transplant included earlier era of implantation (P=0.05), female gender (P=0.02), and congenital disease diagnosis (P=0.05). There was no difference in 5-year survival after transplantation for patients on VAD at time of transplantation as compared with those not requiring VAD. Conclusions— VAD support in children successfully bridged 77% of patients to transplantation, with posttransplantation outcomes comparable to those not requiring VAD. These encouraging results emphasize the need to further understand patient selection and to delineate the impact of VAD technology for children.