Grogan, Martha

Abstract Background Cardiopulmonary exercise testing (CPET) has emerged as an important tool for risk stratification and prognosis assessment in patients with cardiac diseases. The Weber and Ventilatory Functional Classification have been correlated with outcomes in patients with Heart Failure (HF). Weber classification is based on VO2: Weber class A, peak VO2 >20 mL/kg per minute; class B, peak VO2 16–20 mL/kg per minute; class C, peak VO2 10–16 mL/kg per minute; and class D, peak VO2 ≤10 mL/kg per minute and Ventilatory classification on VE/VCO2 slope I-IV (Figure A). Although VO2 and VE/VCO2 variables have found altered in the amyloidosis population, the applicability of this classification in a cohort of amyloidosis patients and its correlation with all-cause mortality have not been explored. Purpose To evaluate if the Weber and Ventilatory Classification of HF predicts mortality amyloidosis patients. Methods 194 with diagnosis of amyloidosis who underwent CPET from February 2010 to February 2024 were included in this retrospective cohort study. Patients with at least one CPET complete data were included in the analysis. Data on the type of amyloidosis, comorbidities, and echocardiogram were retrieved from medical records. Cohort was divided into two groups according to the Weber Classification: Weber Class A/B and Weber Class C/D. Individuals with CPET studies after heart transplant were excluded from the analysis. Statistical analyses including Fisher’s exact test, chi-square, Tukey-Kramer (TK), Cox regression model analysis, proportional hazards model for time to event, and Kaplan–Meier curves were performed. A p-value <0.05 was considered significant. Results Out of the 194 patients, 94 were classified as Weber A-B and 100 as Weber B-C. The age at stress test was similar between the groups: Weber A/B 62.9 ± 11.7 years and Weber C/D 62.3 ± 10.7 years (p=0.087). Ejection Fraction was similar between groups, 32% and 28.9% in A-B and C-D respectively (p =0.207). Higher levels of NT-proBNP were found in the Weber C/D group. The prevalence of comorbidities was balanced among the groups except chronic kidney disease, which was higher in Weber Class C/D (40%) vs (20.2%) in Weber Class A/B (Table 1). Cox analysis revealed a strong association between higher Weber class and the outcome HR 2.36 (1.18 – 4.71) p=0.014. For Higher Ventilatory Class (Group III-IV) similar results were found HR 2.95 (1.60 – 5.45) p=0.005(Table 2). Mortality was significantly higher during the follow-up in the Weber C/D group (25%) vs (10%) in the Weber A-B group p=0.007(Figure D). Conclusion Weber and ventilatory Classification based on CPET, besides predicting outcomes in patients with cardiac disease, are strong predictors of mortality in patients with amyloidosis. These findings suggest that this patient group benefits from earlier stratification to assess prognosis and the potential requirement for transplant independently from other factors.

Abstract Background Cardiopulmonary exercise testing (CPET) is a widely used tool for risk stratification and prognosis in patients with chronic heart failure. In amyloid patients, cardiac amyloid deposits are associated with poor prognosis, increased risk for arrhythmias, sudden death, and subsequent exercise limitation due to restrictive cardiomyopathy. The type of amyloidosis and its affectation of the heart are different, and little is known about the CPET parameters according to the type of cardiac amyloidosis. Purpose In this study, we aim to compare CPET data in different types of amyloidosis to determine if CPET variables evaluated could have a significant difference that could impact the follow-up or prognosis of the patients based on the type of amyloidosis. Methods We conducted a retrospective cohort study of 194 patients with a diagnosis of cardiac amyloidosis referred for CPET from February 2010 to February 2024. Patients with at least one CPET data were included in our analysis. The type of amyloidosis, comorbidities, and echocardiogram data were retrieved from medical records. Patients were divided into 3 different groups according to the type of amyloidosis: AL Amyloidosis(AL), Variant TTR Amyloidosis (vTRR), and Wild Type TTR Amyloidosis (wtTTR). Individuals with CPET studies after heart transplant were excluded from the analysis. Fisher’s exact test or chi-square was used to compare categorical variables. ANOVA and Tukey-Kramer (TK) were used to compare continuous variables. Adjustment using General Linear Models (GLM) procedure was used to identify any confounder that could affect the results. A p-value <0.05 was considered significant. Results Out of the 194 patients, 66 had AL Amyloidosis, 40 had vTTR Amyloidosis, and 88 had wtTTR Amyloidosis. Most of the patients were male, and the male predominance was higher in the wtTRR group. There were 41 (62.1%) males in the AL group, 35 (87.5%) in the vTRR group, and 83 (94.3%) in the wtTTR group (p<0.0001). Comorbidities were balanced among the groups. Additional demographic and comorbidities data are shown in Table 1. From the evaluated CPET variables, VE/VCO2 nadir and slope were significantly higher in the wtTTR group when compared to the other groups, as well as Peak VE and Peak TV(Figure A). However, after adjusting for sex, BMI, and age, VE/VCO2 nadir was still significantly higher in the wtTRR group (p=0.003) compared to the other groups, as well as Peak VE, which was higher again in vTTR patients (p=0.001), and Peak TV (Table 2). Conclusion Ventilation variables evaluated in CPET showed alterations in the wtTTR group. These findings suggest that wtTRR amyloid patients could have a severe problem in ventilation that could be of significant relevance in future prognosis.

Abstract Background/Introduction Patients with ATTR-CM can have lower circulating TTR levels, which is associated with worsening of cardiac function and increased risk of cardiovascular mortality.[1] Acoramidis has been shown to reduce cardiovascular mortality and hospitalization, while increasing circulating TTR levels, in the ATTRibute-CM phase 3 study.[2] Purpose I. Evaluate serum TTR levels in participants (pts) receiving acoramidis vs those who received tafamidis in the placebo group in ATTRibute-CM at Month 30. II. Evaluate serum TTR levels in pts who transitioned from placebo+tafamidis to acoramidis in the open-label long term extension (OLE) study. Methods ATTRibute-CM study: Eligible pts with ATTR-CM were randomized in a 2:1 ratio to receive acoramidis or placebo for 30 months. Pts in both groups had the option of initiating open-label, commercially available tafamidis after 12 months in the study. Upon completion of Month 30, pts were invited to participate in the OLE study. In OLE, pts who had previously received acoramidis continued acoramidis, and those who had previously received placebo+tafamidis were switched to acoramidis-only treatment. All pts in the OLE study received acoramidis only. Change in serum TTR levels in ATTRibute-CM and OLE at data cutoff (Oct 9, 2023) are summarised using descriptive statistics. Results In the phase 3 study, efficacy analyses were performed in 611 pts, of which 61 of 409 (14.9%) and 46 of 202 (22.8%) received tafamidis in acoramidis and placebo groups, respectively. The median time until tafamidis initiation was 17.8 and 16.1 months, respectively; median exposure duration was 11.6 and 10.5 months, for acoramidis and placebo groups, respectively.[3] Change from baseline (CFB) in serum TTR levels remained unchanged at Month 30 in the placebo-only group (mean [SD] = –0.4 [4.92] mg/dL). Characteristics of pts analysed are described in Fig. 1. A total of 380/611 pts (62.2%) entered the OLE study (229 pts continued acoramidis only, and 23 switched from placebo+tafamidis to acoramidis). At the time of data cutoff, 214 pts who had received acoramidis only completed Month 6 in OLE versus 18 who switched from placebo+tafamidis to acoramidis. At Month 30 in ATTRibute-CM, CFB in serum TTR levels were higher for patients who received acoramidis only than those receiving placebo+tafamidis (Fig 2A). Serum TTR levels increased further in pts who switched from placebo+tafamidis to acoramidis in OLE (Fig. 2B). The OLE study is ongoing, and this analysis includes pts who completed the Month 6 visit at time of data-cut. Conclusion(s) CFB in serum TTR levels were higher in pts receiving acoramidis only than those receiving placebo+tafamidis at Month 30 in the double-blind study. A further significant increase in serum TTR levels was observed in those who received placebo+tafamidis and switched to acoramidis in OLE.

Abstract Aims We aim to determine if our previously validated, diagnostic artificial intelligence (AI) electrocardiogram (ECG) model is prognostic for survival among patients with cardiac amyloidosis (CA). Methods A total of 2533 patients with CA (1834 with light chain amyloidosis (AL), 530 with wild-type transthyretin amyloid protein (ATTRwt) and 169 with hereditary transthyretin amyloid (ATTRv)] were included. An amyloid AI ECG (A2E) score was calculated for each patient reflecting the likelihood of CA. CA stage was calculated using the European modification of the Mayo 2004 criteria for AL and Mayo stage for transthyretin amyloid (ATTR). Risk of death was modelled using Cox proportional hazards, and Kaplan–Meier was used to estimate survival. Results Median age of the cohort was 67 [inter-quartile ratio (IQR) 59, 74], and 71.6% were male. The median overall survival for the cohort was 35.6 months [95% confidence interval (CI) 32.3, 39.5]. For AL, ATTRwt and ATTRv, respectively, median survival was 22.9 (95% CI 19.2, 28.2), 47.2 (95% CI 43.4, 52.3) and 61.4 (95% CI 48.7, 75.9) months. On univariate analysis, an increasing A2E score was associated with more than a two-fold risk of all-cause death. On multivariable analysis, the A2E score retained its importance with a risk ratio of 2.0 (95% CI 1.58, 2.55) in the AL group and 2.7 (95% CI 1.81, 4.24) in the ATTR group. Conclusions Among patients with AL and ATTR amyloidosis, the A2E model helps to stratify risk of CA and adds another dimension of prognostication.

Background: Cardiac amyloidosis (CA) is associated with sinus node dysfunction (SND) and conduction system disease (CSD) yet data on pacing indications and outcomes is scarce. Methods: Retrospective review of patients (pts) with CA who had device implantation due to pacing indication at our institution. Results: At total of 51 (mean age 67.2±9.2 years, 90.2% male) pts with immunoglobulin light chain (n=27, 52.9%), hereditary transthyretin (n=7, 13.7%) and wild-type transthyretin (n=17, 33.3%) CA were included. Indication for pacing was exercise intolerance (n=16, 31.4%), syncope (n=16, 31.4%), congestive heart failure (n=5, 9.8%) and palpitation (n=2, 3.9%) with SND (n=23, 45.1%), CSD (17=33.3%) and uncontrolled atrial fibrillation (n=11, 21.6%). 16 (31.4%) pts received defibrillators (ICD) for primary prevention, of whom 8 (15.7%) had left ventricular ejection fraction (LVEF) ≤35%. Atrial (P wave: 1.7±1.2mV, threshold: 1.1±0.5mV/0.5±0.2ms) and right ventricular (RV) (R wave: 7.9±3.8mV, threshold: 0.8±0.4mV/0.4±0.1ms) lead parameters were satisfactory at implantation. During follow-up (mean 36.6±33.6 months), 26 (51%) pts reported symptomatic improvement (SI). Syncope was the only predictor of SI (OR 16.4, 95%CI 1.8-145.2, p=0.01) while exercise intolerance was not (OR 0.09, 95%CI 0.02-0.44, p=0.003). First-time life-threatening ventricular arrhythmias (VA) occurred in 6 (11.8%) pts, 3 (5.9%) had ICD implanted for LVEF ≤35%, 3 (5.9%) without ICD and LVEF ≥35%. Syncope was not predictive of first-time VA. RV lead noise led to inappropriate ICD shocks in 1 patient. Atrial lead sensing failure occurred in 6 (11.8%) and loss of capture in 5 (9.8%). Conclusion: Device implantation in patients with cardiac amyloidosis is safe but atrial lead failure is common. Syncope usually improves with pacing whereas other factors should be considered in those presented with exercise intolerance. Selection of pts who need pacing for prophylactic ICD implantation is challenging as neither left ventricular ejection fraction nor syncope are predictive of arrhythmic events.

Introduction: The subcutaneous implantable cardioverter defibrillator (S-ICD) is an attractive option for patients with congenital heart disease (CHD) in whom a transvenous system is contraindicated. However, more than 10% of adult patients with CHD fail S-ICD screening due to a large T- to R-wave ratio. We hypothesized right-sternal electrodes may permit S-ICD placement in patients who fail left-sternal screen. Methods: We prospectively screened 40 patients with CHD for S-ICD using the standard proprietary approach. We also screened with right sternal electrodes (with left can electrode position). Results: The mean age of the cohort was 46+/-15 years; 24 males were enrolled. CHD anomalies consisted of tetralogy of Fallot (n=11), Ebstein’s anomaly (n=7), atrial septal defect (n=6), dextro-looped transposition of the great artery (n=5) and other (n=11). Left side screening ECG failed in 9 patients (23%), five of whom passed with right sternal electrodes, increasing the pass rate from 77% to 90%. Figure shows the screening ECG and chest x-ray of a patient who failed in all three vectors on the left side but passed in the alternative vector on the right side and underwent right sided implantation. Conclusions: The addition of right sternal electrodes during screening increases S-ICD eligibility and may avoid thoracotomy for high risk patients with CHD.

Abstract Aims Cardiac amyloidosis (CA) is common in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). Cardiac amyloidosis has poor outcomes, and its assessment in all TAVR patients is costly and challenging. Electrocardiogram (ECG) artificial intelligence (AI) algorithms that screen for CA may be useful to identify at-risk patients. Methods and results In this retrospective analysis of our institutional National Cardiovascular Disease Registry (NCDR)-TAVR database, patients undergoing TAVR between January 2012 and December 2018 were included. Pre-TAVR CA probability was analysed by an ECG AI predictive model, with >50% risk defined as high probability for CA. Univariable and propensity score covariate adjustment analyses using Cox regression were performed to compare clinical outcomes between patients with high CA probability vs. those with low probability at 1-year follow-up after TAVR. Of 1426 patients who underwent TAVR (mean age 81.0 ± 8.5 years, 57.6% male), 349 (24.4%) had high CA probability on pre-procedure ECG. Only 17 (1.2%) had a clinical diagnosis of CA. After multivariable adjustment, high probability of CA by ECG AI algorithm was significantly associated with increased all-cause mortality [hazard ratio (HR) 1.40, 95% confidence interval (CI) 1.01–1.96, P = 0.046] and higher rates of major adverse cardiovascular events (transient ischaemic attack (TIA)/stroke, myocardial infarction, and heart failure hospitalizations] (HR 1.36, 95% CI 1.01–1.82, P = 0.041), driven primarily by heart failure hospitalizations (HR 1.58, 95% CI 1.13–2.20, P = 0.008) at 1-year follow-up. There were no significant differences in TIA/stroke or myocardial infarction. Conclusion Artificial intelligence applied to pre-TAVR ECGs identifies a subgroup at higher risk of clinical events. These targeted patients may benefit from further diagnostic evaluation for CA.