Introduction: Cardiopulmonary exercise testing (CPET) is a prognostic tool for advanced heart failure. Whether exercise metrics can provide incremental mortality prediction in ATTRwt-CM has not been well-studied. Hypothesis: We hypothesize CPET metrics improve mortality prediction in ATTRwt-CM. Methods: A retrospective review was conducted in ATTRwt-CM patients evaluated at the BU Amyloidosis Center between 2009-2019 who underwent CPET testing. Baseline demographic, clinical, and mortality data was collected. Continuous and categorical variables were compared using paired t-testing and chi-square testing, respectively. Baseline variable association with mortality was evaluated using logistic regression. Kaplan-Meier curves were used for survival estimation and Hazard ratios (HR) were estimated using Cox proportional hazards regression analysis. Results: A total of 136 patients with ATTRwt-CM were analyzed with median follow-up of 4 years (IQR 2.4, 5.6) with 43% deaths (n=59) during follow-up. Differences in baseline characteristics and metrics between individuals with and without mortality are shown in the table. Peak VO 2 , V E /VCO 2 , ventilatory threshold, heart rate recovery, and OUES were significantly associated with mortality. Using backwards stepwise regression, only OUES remained significantly associated with mortality among CPET variables. Using multivariable Cox survival analysis (adjusting for age, NYHA, eGFR, LVEF, troponin I, and BNP), OUES remained significantly associated with mortality (HR 0.25, 95% CI 0.08 - 0.77; p=0.02). The addition of OUES to troponin I, BNP, GLS, and eGFR increased the Wald chi-square statistic from 22.5 to 26.5 (p=0.01). Conclusions: The addition of OUES in ATTRwt-CM improves mortality prediction when added to current disease staging biomarkers: troponin I, BNP, GLS, and eGFR. This study highlights the incremental strength in outcome prediction using an exercise parameter, OUES, in ATTRwt-CM.
A 29-year-old man presented to our institution with acute, severe substernal chest pain. An ECG on arrival revealed 3mm ST-elevations in the lateral leads with reciprocal depressions in the inferior leads. Troponin-I was above assay (>50 ng/mL). Emergent coronary angiography showed normal coronary arteries, and left ventriculogram showed no wall motion abnormalities. A transthoracic echocardiogram showed normal biventricular size, wall thickness, and ejection fraction (EF). This was his fifth episode of chest pain over the past 10 years, consistent with prior presentations of ST-elevation myocardial infarction and angiographically normal coronary arteries. A prior cardiac magnetic resonance imaging (MRI, 6 years before the current presentation) revealed increased T2 signal intensity and subepicardial late gadolinium enhancement (LGE) in the septum, inferior, and inferolateral walls, suggestive of nonischemic acute myocardial injury. A repeat cardiac MRI during the current presentation showed mildly reduced biventricular systolic function (LVEF 52%, RVEF 36%), and again showed increased T2 signal intensity and subepicardial LGE involving the septum, inferior and inferolateral walls. The anterior and anterolateral walls were also now involved. Endomyocardial biopsy (EMB) showed focal interstitial fibrosis with no evidence of active myocarditis. On telemetry he was noted to have runs of non-sustained ventricular tachycardia (NSVT). Serologic evaluation was negative for parvovirus, cytomegalovirus, and Chagas disease. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Genetic testing was performed at our newly established cardiovascular genetics program, which showed a pathogenic truncating mutation in the desmoplakin gene (DSP). DSP cardiomyopathy (CM) is an LV-predominant arrhythmogenic CM, which can present with episodic myocardial injury, and has a high disposition for ventricular arrhythmias with subepicardial LGE pattern often proceeding LV systolic dysfunction. A primary prevention implantable cardioverter-defibrillator was placed given extent of LGE and NSVT burden in the context of DSP variant. This case illustrates the importance of genetic testing in identifying rare CM phenotypes.
High-dose melphalan and stem cell transplantation (HDM/SCT) is an effective treatment for selected patients with AL amyloidosis. We report the long-term outcomes of 648 patients with AL amyloidosis treated with HDM/SCT over 25 years. Hematologic CR was achieved by 39% of patients. The median duration of hematologic CR was 12.3 years, and 45% of patients with a hematologic CR had no evidence of a recurrent plasma cell dyscrasia at 15 years after HDM/SCT. With a median follow-up interval of 8 years, the median event-free survival (EFS) and overall survival (OS) were 3.3 and 7.6 years, respectively. Patients with a hematologic CR had a median OS of 15 years, and 30% of these patients survived >20 years. On multivariable analysis, dFLC >180 mg/L and BM plasma cells >10% were independently associated with shorter EFS, whereas BNP >81 pg/mL, troponin I > 0.1 ng/mL, and serum creatinine >2.0 mg/dL were independently associated with shorter OS. We developed a prognostic score for EFS, which incorporated dFLC >180 mg/L and BMPC% >10% as adverse risk factors. Patients with low-risk (0 factors), intermediate-risk (1 factor), and high-risk (2 factors) disease had median EFS estimates of 5.3, 2.8, and 1.0 years, respectively (p < .001). The 100-day treatment-related mortality rate was 3% in the latest treatment period (2012-2021), and the 25-year risk of t-MDS/AML was 3%. We conclude that HDM/SCT induces durable hematologic responses and prolonged survival with improved safety in selected patients with AL amyloidosis.
