Jeffrey J. Teuteberg

Statement Regarding the Pre and Post Market Assessment of Durable, Implantable Ventricular Assist Devices in the United States

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients who have advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and Interagency Registry of Mechanically Assisted Circulatory Support.

Statement Regarding the Pre and Post Market Assessment of Durable, Implantable Ventricular Assist Devices in the United States: Executive Summary

The incorporation of complex medical device technologies into clinical practice is governed by critical oversight of the US Food and Drug Administration. This regulatory process requires a judicious balance between assuring safety and efficacy, while providing efficient review to facilitate access to innovative therapies. Recent contrasting views of the regulatory process have emphasized the difficulties in obtaining an optimal balance. Mechanical circulatory support has evolved to become an important therapy for patients with advanced heart failure with the advent of more durable, implantable ventricular assist devices. The regulatory oversight of these new technologies has been difficult owing to the complexities of these devices, associated adverse event profile, and severity of illness of the intended patient population. Maintaining a regulatory environment to foster efficient introduction of safe and effective technologies is critical to the success of ventricular assist device therapy and the health of patients with advanced heart failure. Physicians representing key surgical and cardiology societies, and representatives from the Food and Drug Administration, National Heart, Lung, and Blood Institute, Centers for Medicare and Medicaid Services, Interagency Registry of Mechanically Assisted Circulatory Support, and industry partners gathered to discuss relevant issues regarding the current regulatory environment assessing ventricular assist devices. The goal of the meeting was to explore innovative ways to foster the introduction of technologically advanced, safe, and effective ventricular assist devices. The following summary reflects opinions and conclusions endorsed by The Society of Thoracic Surgeons, American Association for Thoracic Surgery, American Heart Association, Heart Failure Society of America, International Society for Heart and Lung Transplantation, and the Interagency Registry of Mechanically Assisted Circulatory Support.

Right ventricular load adaptability metrics in patients undergoing left ventricular assist device implantation

Objective: Several right load adaptability metrics have been proposed as predictors of right heart failure (RHF) following left ventricular assist device implantation. This study sought to validate and compare the prognostic value of these indices. Methods: This retrospective study included 194 patients undergoing continuous‐flow left ventricular assist device implantation. The primary end point was unplanned right atrial assist device (RVAD) need within 30 days after left ventricular assist device implantation; the secondary end points included clinical RHF syndrome without RVAD need and the composite of RHF or RVAD need. Load adaptability indices or interventricular ratios were divided into surrogates of ventriculoarterial coupling (RV area change:end‐systolic area), indices reflecting adaptation proportionality (Dandels index = tricuspid regurgitation velocity‐time integral normalized for average RV radius in diastole or systole), and simple ratios (eg, pulse pressure:right atrial pressure or right arterial pressure:pulmonary arterial wedge pressure). Results: Mean age was 55 ± 13 years with 77% of men. RHF occurred in 75 patients with 30 patients requiring RVAD implantation. Among right heart metrics, right arterial pressure (normalized odd ratio, 1.62; 95% confidence interval, 1.15‐2.38), right arterial pressure:pulmonary arterial wedge pressure (normalized odds ratio, 1.59; 95% confidence interval, 1.08‐2.32) and pulse pressure:right arterial pressure < 2.0 (normalized odds ratio, 2.56; 95% confidence interval, 1.16‐5.56) were associated with RVAD need (all P values < .02). These 3 metrics significantly added incremental prognostic value to the Interagency Registry for Mechanically Assisted Circulatory Support classification score in a similar range, whereas only RAP was incremental to the Michigan score. Correlates of RHF not requiring RVAD included RV end‐systolic area index and the Dandel indices, which provided similar incremental value to the Interagency Registry for Mechanically Assisted Circulatory Support, Michigan, and European Registry for Patients with Mechanical Circulatory Support scores. Conclusions: Although associated with outcome, right load adaptability indices do not appear to provide strong incremental value when compared with simple metrics.

A Bayesian Model to Predict Survival After Left Ventricular Assist Device Implantation

OBJECTIVESnThis study investigates the use of a Bayesian statistical models to predict survival at various time points in patients undergoing left ventricular assist device (LVAD) implantation.nnnBACKGROUNDnLVADs are being increasingly used in patients with end-stage heart failure. Appropriate patient selection continues to be key in optimizing post-LVAD outcomes.nnnMETHODSnData used for this study were derived from 10,277 adult patients from the INTERMACS (Inter-Agency Registry for Mechanically Assisted Circulatory Support) who had a primary LVAD implanted between January 2012 and December 2015. Risk for mortality was calculated retrospectively for various time points (1, 3, and 12 months) after LVAD implantation, using multiple pre-implantation variables. For each of these endpoints, a separate tree-augmented naïve Bayes model was constructed using the most predictive variables.nnnRESULTSnA set of 29, 26, and 31 pre-LVAD variables were found to be predictive at 1, 3, and 12 months, respectively. Predictors of 1-month mortality included low Inter-Agency Registry for Mechanically Assisted Circulatory Support profile, number of acute events in the 48 h before surgery, temporary mechanical circulatory support, and renal and hepatic dysfunction. Variables predicting 12-month mortality included advanced age, frailty, device strategy, and chronic renal disease. The accuracy of all Bayesian models was between 76% and 87%, with an area under the receiver operative characteristics curve of between 0.70 and 0.71.nnnCONCLUSIONSnA Bayesian prognostic model for predicting survival based on the comprehensive INTERMACS registryxa0provided highly accurate predictions of mortality based on pre-operative variables. These models may facilitatexa0clinical decision-making while screening candidates for LVAD therapy.

Accepting hepatitis C virus-infected donor hearts for transplantation: Multistep consent, unrealized opportunity, and the Stanford experience

The current mismatch between supply and demand of organs has prompted transplant clinicians to consider innovative solutions to broaden the donor pool. Advancements of direct‐acting antiviral agent (DAA) therapy for hepatitis C virus (HCV) have allowed entertaining the use of viremic donor organs in nonviremic recipients. In this report, we describe the evolution of HCV treatment, ethics and informed consent, cost‐effectiveness of HCV medications in treating acute HCV post‐transplantation, and the Stanford experience with two HCV‐viremic donor heart transplantations. We describe excellent short‐term outcomes post–heart transplantation with HCV NAT‐positive organs. The availability of this therapy may expand the donor pool. While we await larger‐scale clinical data on the effectiveness and safety of DAA therapy in patients after heart transplantation, many transplant centers have already started accepting organs from HCV‐infected donors, balancing the unknown long‐term risks versus the benefits of shorter wait times and expansion of the donor pool. Protocols and multidisciplinary teams are needed to effectively communicate risk to potential recipients, to ensure timely DAA access, and to implement appropriate clinical follow‐up in order to achieve excellent clinical outcomes and to maximize the donor pool by utilizing HCV‐infected organs for heart transplantation.

The 2018 ISHLT/APM/AST/ICCAC/STSW Recommendations for the Psychosocial Evaluation of Adult Cardiothoracic Transplant Candidates and Candidates for Long-term Mechanical Circulatory Support

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs unique needs and goals.

The 2018 ISHLT/APM/AST/ICCAC/STSW recommendations for the psychosocial evaluation of adult cardiothoracic transplant candidates and candidates for long-term mechanical circulatory support

The psychosocial evaluation is well-recognized as an important component of the multifaceted assessment process to determine candidacy for heart transplantation, lung transplantation, and long-term mechanical circulatory support (MCS). However, there is no consensus-based set of recommendations for either the full range of psychosocial domains to be assessed during the evaluation, or the set of processes and procedures to be used to conduct the evaluation, report its findings, and monitor patients receipt of and response to interventions for any problems identified. This document provides recommendations on both evaluation content and process. It represents a collaborative effort of the International Society for Heart and Lung Transplantation (ISHLT) and the Academy of Psychosomatic Medicine, American Society of Transplantation, International Consortium of Circulatory Assist Clinicians, and Society for Transplant Social Workers. The Nursing, Health Science and Allied Health Council of the ISHLT organized a Writing Committee composed of international experts representing the ISHLT and the collaborating societies. This Committee synthesized expert opinion and conducted a comprehensive literature review to support the psychosocial evaluation content and process recommendations that were developed. The recommendations are intended to dovetail with current ISHLT guidelines and consensus statements for the selection of candidates for cardiothoracic transplantation and MCS implantation. Moreover, the recommendations are designed to promote consistency across programs in the performance of the psychosocial evaluation by proposing a core set of content domains and processes that can be expanded as needed to meet programs unique needs and goals.

Substantial Reduction in Driveline Infection Rates With the Modification of Driveline Dressing Protocol

BACKGROUNDnDriveline infection (DLI) is a cause of morbidity and mortality in patients with continuous-flow left ventricular assist devices (CF-LVADs). We hypothesized that an alternate dressing protocol would decrease the rate of DLIs.nnnMETHODS AND RESULTSnA retrospective review of CF-LVAD implants at a single institution from January 2010 to October 2015 was conducted. Patients were divided into implants before (group 1) and after (group 2) the introduction of the new protocol on September 1, 2012. Patients were followed until death, transplantation, change in dressing type, or 2 years. 153 patients were included: 61 in group 1 and 92 in group 2. Group 1 had fewer HVADs than group 2 (27.9% vs 71.7%; P < .001) and more destination therapy, although the latter was not statistically significant (50.8% vs 34.8%; Pu202f=u202f.118). At 24 months, the freedom from DLI was 53% in group 1 and 89% in group 2 (Pu202f=u202f.01). Group 1 had a significantly greater risk of DLI than group 2 (incident rate ratio 3.18, 95% confidence interval 1.23-8.18; Pu202f=u202f.016).nnnCONCLUSIONSnDramatic improvement in freedom from DLI at 2 years was achieved with a new driveline dressing protocol. This demonstrates that DLI rates can be improved with alternate percutaneous site care techniques in CF-LVAD patients.

New Horizons on the 50th Anniversary of Heart Transplantation in Canada: “Where There Is Death, There Is Hope”

Journal News and Commentary New Horizons on the 50th Anniversary of Heart Transplantation in Canada: “Where There Is Death, There Is Hope” Yasbanoo Moayedi, MD, Mosaad Alhussein, MD, Juan G. Duero Posada, MD, Stella Kozuszko, RN(EC), MN, NP-Adult, Kiran K. Khush, MD, MAS, Jeffrey J. Teuteberg, MD, Mitesh V. Badiwala, MD, PhD, and Heather J. Ross, MD, MHSc Ted Rogers Centre of Excellence in Heart Function, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada Department of Cardiovascular Medicine, Heart Transplant Program, Stanford University, Stanford, California, USA Department of Cardiovascular Surgery, Peter Munk Cardiac Centre, University Health Network, Toronto, Ontario, Canada