Lyle, Melissa A

AbstractBackgroundThe prognosis in patients with advanced cardiac amyloidosis (CA) remains poor.ObjectivesWe sought to describe survival post heart transplantation (HT) in amyloid compared with non‐amyloid recipients, highlight waitlist times within the new allocation system across three Organ Procurement and Transplantation Network (OPTN) regions, and describe multiorgan transplantation (MOT) in hereditary amyloidosis.MethodsThis is a retrospective review of end‐stage CA patients who underwent HT at Mayo Clinic from January 2007 to December 2020. Wait time was compared in the new versus old OPTN allocation era starting December 18, 2018 by Wilcoxon rank sum test. All‐cause mortality for those with and without CA was compared using Kaplan–Meier estimates with log rank analysis, censoring December 16, 2022.ResultsFifty‐five patients with CA underwent HT between 2007 and 2020, 8 light chain amyloidosis (AL) (14.5%), 28 hereditary transthyretin (ATTRv) (50.9%), 17 wildtype transthyretin (ATTRwt) (30.9%), and 2 hereditary apolipoprotein A1 (AApoA1) amyloidosis patients (3.6%). No significant difference in overall survival post‐transplant was seen in amyloid compared with non‐amyloid (p = 0.816). Median time to HT was shorter in the new system, 45 days (IQR 24, 78) versus 174 days (IQR 76.5, 483.5), p = 0.006. There was a decline in MOT in hereditary amyloidosis over time with the concomitant rise in disease‐targeted therapies.ConclusionsHT survival in CA patients was similar to non‐amyloid patients. The new allocation system benefits this cohort with shorter wait times. There is less MOT in hereditary amyloidosis with increased utilization of disease‐targeted therapy.

Objective. To determine the prevalence of monoclonal gammopathy of undetermined significance (MGUS) in patients with PH as well as precapillary PH. Methods. Olmsted County residents with PH, diagnosed between 1/1/1995 and 9/30/2017, were identified, and age and sex were matched to a normal control group. The PH group and normal control group were then cross-referenced with the Mayo Clinic MGUS database. Charts were reviewed to verify MGUS and PH. Heart catheterization data were then analyzed in these patients for reference to the gold standard for diagnosis. Results. There were 3419 patients diagnosed with PH by echocardiography between 1995 and 2017 in Olmsted County that met the criteria of our study. When the PH group (N = 3313) was matched to a normal control group (3313), a diagnosis of MGUS was significantly associated with PH 10.2% (OR = l.84 [95% CI 1.5–2.2], p < 0.001 ), compared with controls 5.8% based on echo diagnosis. Using heart catheterization data (484 patients), a diagnosis of MGUS was associated with PH 13.0% (OR = 3.94 [95% CI 2.28–6.82], p < 0.001 ). For pulmonary artery hypertension (N = 222), a diagnosis of MGUS was associated with PH at similar 12.2% (OR = 4.50 [95%CI 1.86–10.90], p < 0.001 . Conclusions. There is a higher prevalence of MGUS in patients with PH and precapillary PH compared with normal controls. This association cannot be explained fully by other underlying diagnoses associated with PH. Assessing for this in patients with PH of unclear etiology may be reasonable in the workup of patients found to have PH.

AbstractLittle is known about the post heart transplantation management of extra cardiac manifestations in patients with hereditary transthyretin amyloid cardiomyopathy (hATTR‐CM) in the new era of disease modifying treatment for ATTR amyloidosis. This is a retrospective study of all patients with hATTR‐CM associated with the Val142Ile variant who underwent heart transplantation (HT) from January 2014 to February 2022. All 10 patients with the Val142Ile mutation were successfully transplanted, with a 1 year survival post heart transplantation (HT) of 90%, comparable to an age, sex, and race matched cohort of patients transplanted for non‐amyloid indications. However, 4 (40%) of these patients developed progressive extracardiac manifestations requiring initiation of TTR silencer therapy with the small interfering RNA (siRNA) drug patisiran, which was well tolerated with no significant side effects in this population. We recommend formal neurologic evaluation and assessment of extracardiac manifestations annually as part of routine post‐transplant care, and disease modifying therapy, aimed at TTR stabilization or silencing, should be initiated in the context of previously untreated extracardiac manifestations or evidence of subclinical neuropathy to prevent progression.