The 2016 International Society for Heart Lung Transplantation listing criteria for heart transplantation: A 10-year update

The ISHLT Infectious Diseases, Pediatric and Heart Failure and Transplantation Councils Councils, and on behalf of the International Society for Heart Lung Trans transplantation (ISHLT) Infectious diseases, pediatric and heart failure and transplantation councilss are represented.

Abstract

In 2005, the International Society for Heart and Lung Transplantation (ISHLT) Board of Directors commissioned the development of the first International Listing Criteria for Heart Transplantation, published in 2006.1Mehra M.R. Kobashigawa J. Starling R. et al.Listing criteria for heart transplantation: International Society for Heart and Lung Transplantation guidelines for the care of cardiac transplant candidates—2006.J Heart Lung Transplant. 2006; 25: 1024-1042Abstract Full Text Full Text PDF PubMed Scopus (648) Google Scholar Subsequently, the ISHLT commissioned a focused update to concentrate on evolving areas of importance, not fully addressed previously. These include congenital heart disease (CHD), restrictive cardiomyopathy, and infectious diseases. In addition, we undertook a review of all 2006 guidelines to update those where new information was evident or evolution in practice demanded significant changes. All recommendations from the prior guideline were reviewed and the details of the older and newer versions are comprehensively summarized in Table 1. Specific areas of changes are discussed with the supporting evidence.Table 1A Comparison of the 2006 vs 2016 Guidelines for Section I (General Considerations)2006 Guideline recommendation2016 Guideline recommendation1.1. Cardiopulmonary stress testing to guide transplant listing1.1. Cardiopulmonary stress testing to guide transplant listingA maximal cardiopulmonary exercise test is defined as one with a respiratory exchange ratio (RER) > 1.05 and achievement of an anaerobic threshold on optimal pharmacologic therapy (Class I, Level of Evidence: B).Continuing approval without change.The presence of a CRT device does not alter the current peak Vo2 cutoff recommendations (Class I, Level of Evidence: B).In patients intolerant of a β-blocker, a cutoff for peak oxygen consumption (Vo2) of ≤ 14 ml/kg/min should be used to guide listing (Class I, Level of Evidence: B).Continuing approval without change.In the presence of a β-blocker, a cutoff for peak Vo2 of ≤ 12 ml/kg/min should be used to guide listing (Class I, Level of Evidence: B).Continuing approval without change.In young patients ( 35 as a determinant in listing for transplantation may be considered (Class IIb, Level of Evidence: C).Continuing approval without change.In obese (body mass index [BMI] > 30 kg/m2) patients, adjusting peak Vo2 to lean body mass may be considered. A lean body mass–adjusted peak Vo2 of 12 and 3Wood units while maintaining a systolic arterial blood pressure > 85 mm Hg (Class I, Level of Evidence: C).Continuing approval without change.When an acute vasodilator challenge is unsuccessful, hospitalization with continuous hemodynamic monitoring should be performed, as often the PVR will decline after 24 to 48 hours of treatment consisting of diuretics, inotropes and vasoactive agents such as inhaled nitric oxide (Class I, Level of Evidence: C).Continuing approval without change.If medical therapy fails to achieve acceptable hemodynamics, and if the left ventricle cannot be effectively unloaded with mechanical adjuncts, including an intra-aortic balloon pump (IABP) and/or left ventricular assist device (LVAD), it is reasonable to conclude that the pulmonary hypertension is irreversible (Class IIb, Level of Evidence: C).If medical therapy fails to achieve acceptable hemodynamics and if the left ventricle cannot be effectively unloaded with mechanical adjuncts, including an intra-aortic balloon pump (IABP) and/or left ventricular assist device (LVAD), it is reasonable to conclude that the pulmonary hypertension is irreversible. After LVAD, reevaluation of hemodynamics should be done after 3 to 6 months to ascertain reversibility of pulmonary hypertension (Class IIA, Level of Evidence: C).1.4. Comorbidities and their implications for heart transplantation listing1.4. Comorbidities and their implications for heart transplantation listing1.4.1. Age, obesity, and cancer1.4.1. Age, obesity, and cancerPatients should be considered for cardiac transplantation if they are ≤ 70 years of age (Class I, Level of Evidence: C).Continuing approval without change.Carefully selected patients > 70 years of age may be considered for cardiac transplantation. For centers considering these patients, the use of an alternate-type program (i.e., use of older donors) may be pursued (Class IIb, Level of Evidence: C).Carefully selected patients > 70 years of age may be considered for cardiac transplantation (Class IIb, Level of Evidence: C).Overall, pre-transplant BMI > 30 kg/m2 or percent ideal body weight (PIBW) > 140% are associated with poor outcome after cardiac transplantation. For obese patients, it is reasonable to recommend weight loss to achieve a BMI of 35 kg/m2 is associated with a worse outcome after cardiac transplantation. For such obese patients, it is reasonable to recommend weight loss to achieve a BMI of ≤ 35 kg/m2 before listing for cardiac transplantation (Class IIa, Level of Evidence: C).Pre-existing neoplasms are diverse, and many are treatable with excision, radiotherapy, or chemotherapy to induce cure or remission. In these patients needing cardiac transplantation, collaboration with oncology specialists should occur to stratify each patient as to their risk of tumor recurrence. Cardiac transplantation should be considered when tumor recurrence is low based on tumor type, response to therapy, and negative metastatic work-up. The specific amount of time to wait to transplant after neoplasm remission will depend on the aforementioned factors and no arbitrary time period for observation should be used (Class I, Level of Evidence: C).Continuing approval without change.1.4.2. Diabetes, renal dysfunction, and peripheral vascular disease1.4.2. Diabetes, renal dysfunction, and peripheral vascular diseaseDiabetes with end-organ damage other than non-proliferative retinopathy or poor glycemic control (glycosylated hemoglobin [HbA1c] > 7.5%) despite optimal effort is a relative contraindication for transplant (Class IIa, Level of Evidence: C).Diabetes with end-organ damage (other than non-proliferative retinopathy) or persistent poor glycemic control (glycosylated hemoglobin [HbA1c] > 7.5% or 58 mmol/mol) despite optimal effort is a relative contraindication for transplant (Class IIa, Level of Evidence: C).Renal function should be assessed using estimated glomerular filtration rate (eGFR) or creatinine clearance under optimal medical therapy. Evidence of abnormal renal function should prompt further investigation, including renal ultrasonography, estimation for proteinuria, and evaluation for renal arterial disease, to exclude intrinsic renal disease. It is reasonable to consider the presence of irreversible renal dysfunction (eGFR 70 years of age may be considered for cardiac transplantation (Class IIb, Level of Evidence: C). Goldstein et al10Goldstein D.J. Bello R. Shin J.J. et al.Outcomes of cardiac transplantation in septuagenarians.J Heart Lung Transplant. 2012; 31: 679-685Abstract Full Text Full Text PDF PubMed Scopus (16) Google Scholar reported the outcomes of cardiac transplantation in septuagenarians who were carefully evaluated and underwent HT in the United States. These patients derived benefit from this therapy, suffering less rejection but a higher mortality than those slightly younger. Most programs that are performing transplantation in patients aged >70 years are doing so with both specific donor and recipient criteria in place. Therefore, the need to state use of an “alternative allocation” program was felt to be unnecessary and adds to confusion. Nevertheless, local policies to define the upper age limit for eligibility to transplant should be placed into the context of local organ availability and quality in order to maintain acceptable transplant outcomes and a reasonable chance to transplant all listed patients. Recommendation: A pre-transplant body mass index (BMI) >35 kg/m2 is associated with a worse outcome after cardiac transplantation. For such obese patients, it is reasonable to recommend weight loss to achieve a BMI of ≤35 kg/m2 before listing for cardiac transplantation (Class IIa, Level of Evidence: C). Several reports have been published since the 2006 guidelines regarding the effect of BMI on outcomes after HT.11Weiss E.S. Allen J.G. Russell S.D. Shah A.S. Conte J.V. Impact of recipient body mass index on organ allocation and mortality in orthotopic heart transplantation.J Heart Lung Transplant. 2009; 28: 1150-1157Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar, 12Russo M.J. Hong K.N. Davies R.R. et al.The effect of body mass index on survival following heart transplantation: do outcomes support consensus guidelines?.Ann Surg. 2010; 251: 144-152Crossref PubMed Scopus (66) Google Scholar, 13Macha M. Molina E.J. Franco M. et al.Pre-transplant obesity in heart transplantation: are there predictors of worse outcomes?.Scand Cardiovasc J. 2009; 43: 304-310Crossref PubMed Scopus (12) Google Scholar BMI in the obese range but 35 kg/m2 had longer waiting times, were less likely to find a suitable donor, and in some reports had an increase in post-transplant morbidity and mortality. On the basis of these data, the guideline has been amended to recommend that patients achieve a BMI ≤ 35 kg/m2 for listing. Because BMI is the parameter used most often, we opted to remove percentage ideal body weight 7.5% or 58 mmol/mol), despite optimal effort, is a relative contraindication for transplant (Class IIa, Level of Evidence: C). The addition of a HbA1c value of 58 mmol/mol was added to be comprehensive and internationally relevant. Recommendation: Renal function should be assessed using the estimated glomerular filtration rate (eGFR) or creatinine clearance under optimal medical therapy. Evidence of abnormal renal function should prompt further investigation, including renal ultrasonography, estimation of proteinuria, and evaluation for renal arterial disease, to exclude intrinsic renal disease. It is reasonable to consider the presence of irreversible renal dysfunction (eGFR < 30 ml/min/1.73 m2) as a relative contraindication for HT alone (Class IIa, Level of Evidence: C). Renal dysfunction continues to play an important role in outcomes after HT. More often than not, committees are forced to make decisions regarding HT alone, heart-kidney transplant, or deferring transplantation altogether. Unfortunately, which test or formula required to determine irreversible renal dysfunction has not been fully elucidated, with several prevalent formulas to measure eGFR. In the current guidelines, the eGFR, a measure of renal function, was reduced to < 30 ml/min/1.73 m2 to be considered as a relative contraindication for HT. Recommendation: Clinically severe symptomatic cerebrovascular disease (CVD) may be considered a contraindication to transplantation. Peripheral vascular disease may be considered a relative contraindication for transplantation when its presence limits rehabilitation and revascularization is not a viable option (Class IIb, Level of Evidence: C). Cerebrovascular accidents are a devastating complication after transplant surgery and can greatly alter quality of life and survival. The prior guideline included “not amenable to revascularization” in its