Citations

AbstractBackgroundAmyloidosis is a systemic disorder of abnormal protein folding and deposition resulting in a range of symptoms including neuropathy, heart failure, renal disease, and dermatologic findings. The two most common types of amyloidosis that affect the heart are transthyretin (ATTR) amyloidosis and light chain (AL) amyloidosis, which vary in clinical presentation. Skin findings such as periorbital purpura are considered more specific for AL amyloidosis. However, there are rare cases of ATTR amyloidosis causing the same dermatologic findings.Case SummaryA 69-year-old female presented for evaluation of amyloidosis after cardiac imaging done at the time of a recent atrial fibrillation ablation showed signs of infiltrative disease. On examination, she had periorbital purpura which she reportedly had for years without receiving a diagnosis, as well as macroglossia with teeth indentation. These exam findings, in addition to her transthoracic echocardiogram showing apical sparing, are typically considered characteristic of AL amyloidosis. Subsequent workup revealed the presence of hereditary ATTR (hATTR) amyloidosis with a heterozygous pathogenic variant in the TTR gene producing the p.Thr80Ala mutation.ConclusionSpontaneous periorbital purpura is thought to be pathognomonic for AL amyloidosis. However, we describe a case of hereditary ATTR amyloidosis with the Thr80Ala TTR genetic variant presenting initially with periorbital purpura, the first case documented in the literature to our knowledge.

Abstract Aims Current non-invasive screening methods for cardiac allograft rejection have shown limited discrimination and are yet to be broadly integrated into heart transplant care. Given electrocardiogram (ECG) changes have been reported with severe cardiac allograft rejection, this study aimed to develop a deep-learning model, a form of artificial intelligence, to detect allograft rejection using the 12-lead ECG (AI-ECG). Methods and results Heart transplant recipients were identified across three Mayo Clinic sites between 1998 and 2021. Twelve-lead digital ECG data and endomyocardial biopsy results were extracted from medical records. Allograft rejection was defined as moderate or severe acute cellular rejection (ACR) based on International Society for Heart and Lung Transplantation guidelines. The extracted data (7590 unique ECG-biopsy pairs, belonging to 1427 patients) was partitioned into training (80%), validation (10%), and test sets (10%) such that each patient was included in only one partition. Model performance metrics were based on the test set (n = 140 patients; 758 ECG-biopsy pairs). The AI-ECG detected ACR with an area under the receiver operating curve (AUC) of 0.84 [95% confidence interval (CI): 0.78–0.90] and 95% (19/20; 95% CI: 75–100%) sensitivity. A prospective proof-of-concept screening study (n = 56; 97 ECG-biopsy pairs) showed the AI-ECG detected ACR with AUC = 0.78 (95% CI: 0.61–0.96) and 100% (2/2; 95% CI: 16–100%) sensitivity. Conclusion An AI-ECG model is effective for detection of moderate-to-severe ACR in heart transplant recipients. Our findings could improve transplant care by providing a rapid, non-invasive, and potentially remote screening option for cardiac allograft function.

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.

AbstractBackgroundAs targeted treatments for amyloid transthyretin cardiomyopathy (ATTR‐CM) are becoming available, we aim to characterize the rates of ventricular arrhythmias (VAs), implantable cardioverter‐defibrillator (ICD) utilization, and their impact on survival.MethodsThis is a retrospective cohort study of 130 patients with ATTR‐CM diagnosed at Emory University's Cardiac Amyloidosis Center between April 2012 and September 2020. VAs were defined as nonsustained or sustained ventricular tachycardia and ventricular fibrillation.ResultsOf 130 patients, 42 had wild‐type disease (wtATTR) and 88 had hereditary variants (hATTR), most commonly Val122Ile (89%). At ATTR‐CM diagnosis, 80 (62%) patients had EF ≤ 40% consistent with systolic heart failure. Of the 69 (53%) patients with documented VAs significantly higher rates occurred among those with EF ≤ 40% compared with EF > 40% (67% vs. 28%, p = .001). Thirty‐two patients (25 hATTR, 7 wtATTR) had primary prevention ICDs implanted. Eight (25%) of these patients received appropriate ICD therapy while two (6%) experienced inappropriate therapy. Comparing patients with EF ≤ 35% with and without ICDs did not reveal any survival difference (3.3 ± 0.5 vs. 2.8 ± 0.4 years, p = .699).ConclusionsHigh rates of VAs and appropriate ICD therapy were found among a unique cohort of largely hereditary ATTR‐CM patients with a high rate of systolic heart failure.

Background The prognosis of left ventricular noncompaction (LVNC) remains elusive despite its recognition as a clinical entity for >30 years. We sought to identify clinical and imaging characteristics and risk factors for mortality in patients with LVNC. Methods and Results 339 adults with LVNC seen between 2000 and 2016 were identified. LVNC was defined as end‐systolic noncompacted to compacted myocardial ratio >2 (Jenni criteria) and end‐diastolic trough of trabeculation‐to‐epicardium (X):peak of trabeculation‐to‐epicardium (Y) ratio <0.5 (Chin criteria) by echocardiography; and end‐diastolic noncompacted:compacted ratio >2.3 (Petersen criteria) by magnetic resonance imaging. Median age was 47.4 years, and 46% of patients were female. Left ventricular ejection fraction <50% was present in 57% of patients and isolated apical noncompaction in 48%. During a median follow‐up of 6.3 years, 59 patients died. On multivariable Cox regression analysis, age (hazard ratio [HR] 1.04; 95% CI, 1.02–1.06), left ventricular ejection fraction <50% (HR, 2.37; 95% CI, 1.17–4.80), and noncompaction extending from the apex to the mid or basal segments (HR, 2.11; 95% CI, 1.21–3.68) were associated with all‐cause mortality. Compared with the expected survival for age‐ and sex‐matched US population, patients with LVNC had reduced overall survival ( P <0.001). However, patients with LVNC with preserved left ventricular ejection fraction and patients with isolated apical noncompaction had similar survival to the general population. Conclusions Overall survival is reduced in patients with LVNC compared with the expected survival of age‐ and sex‐matched US population. However, survival rate in those with preserved left ventricular ejection fraction and isolated apical noncompaction was comparable with that of the general population.