Tseng, Andrew S.

Abstract Aims The increasing need for diagnostic echocardiography tests presents challenges in preserving the quality and promptness of reports. While Large Language Models (LLMs) have proven effective in summarizing clinical texts, their application in echo remains underexplored. Methods and results Adult echocardiography studies, conducted at the Mayo Clinic from 1 January 2017 to 31 December 2017, were categorized into two groups: development (all Mayo locations except Arizona) and Arizona validation sets. We adapted open-source LLMs (Llama-2, MedAlpaca, Zephyr, and Flan-T5) using In-Context Learning and Quantized Low-Rank Adaptation fine-tuning (FT) for echo report summarization from ‘Findings’ to ‘Impressions.’ Against cardiologist-generated Impressions, the models’ performance was assessed both quantitatively with automatic metrics and qualitatively by cardiologists. The development dataset included 97 506 reports from 71 717 unique patients, predominantly male (55.4%), with an average age of 64.3 ± 15.8 years. EchoGPT, a fine-tuned Llama-2 model, outperformed other models with win rates ranging from 87% to 99% in various automatic metrics, and produced reports comparable to cardiologists in qualitative review (significantly preferred in conciseness (P < 0.001), with no significant preference in completeness, correctness, and clinical utility). Correlations between automatic and human metrics were fair to modest, with the best being RadGraph F1 scores vs. clinical utility (r = 0.42) and automatic metrics showed insensitivity (0–5% drop) to changes in measurement numbers. Conclusion EchoGPT can generate draft reports for human review and approval, helping to streamline the workflow. However, scalable evaluation approaches dedicated to echo reports remains necessary.

AbstractIntroductionAlthough prior studies indicate that a QTc > 500 ms on a single baseline 12‐lead electrocardiogram (ECG) is associated with significantly increased risk of arrhythmic events in long QT syndrome (LQTS), less is known about the risk of persistent QT prolongation. We sought to determine QTc persistence and its prognostic effect on breakthrough cardiac events (BCEs) among pediatric patients treated for LQTS.MethodsWe performed a retrospective analysis of 433 patients with LQTS evaluated, risk‐stratified, and undergoing active guideline‐based LQTS treatment between 1999 and 2019. BCEs were defined as arrhythmogenic syncope/seizure, sudden cardiac arrest (SCA), appropriate VF‐terminating ICD shock, and sudden cardiac death (SCD).ResultsDuring the median follow‐up of 5.5 years (interquartile range [IQR] = 3–9), 32 (7%) patients experienced a total of 129 BCEs. A maximum QTc threshold of 520 ms and median QTc threshold of 490 ms were determined to be strong predictors for BCEs. A landmark analysis controlling for age, sex, genotype, and symptomatic status demonstrated models utilizing both the median QTc and maximum QTc demonstrated the highest discriminatory value (c‐statistic = 0.93–0.95). Patients in the high‐risk group (median QTc > 490 ms and maximum QTc > 520 ms) had a significantly lower BCE free survival (70%–81%) when compared to patients in both medium‐risk (93%–97%) and low‐risk (98%–99%) groups.ConclusionsThe risk of BCE among patients treated for LQTS increases not only based upon their maximum QTc, but also their median QTc (persistence of QTc prolongation). Patients with a maximum QTc > 520 ms and median QTc > 490 ms over serial 12‐lead ECGs are at the highest risk of BCE while on guideline‐directed medical therapy.

Introduction: Peripheral artery disease impacts 202 million patients worldwide and is commonly diagnosed via ankle-brachial index. PAD is associated with endothelial dysfunction, which is also common to venous thromboembolism formation. Despite the suspected overlap in pathogenesis, few studies exist investigating the association between these pathologies. We investigated whether PAD with low or elevated ABI is an independent risk factor for VTE. Methods: We reviewed medical records of patients ≥18 years old undergoing ABI measurement with or without PAD symptoms from 01/01/1996 to 08/31/2018 and classified patients by ABI: severely low (ABI 0.00-0.39), moderately low (0.40-0.69), mildly low (0.70-0.90), borderline (0.91-0.99), normal (1.00-1.40), and elevated (>1.40). The primary outcome was incident VTE event after ABI measurement, defined as deep vein thrombosis or pulmonary embolism. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals after adjusting for age, sex, active smoking, cancer or VTE history, thrombophilia, anticoagulation, and revascularization within 14 days of VTE. Results: In 39,384 unique patients (mean age 66.3±14.2 years, median follow-up 34 months), 5,141 VTE events were observed. Increased VTE risk was observed in PAD patients with severely low ABI (HR 1.26, 95%CI [1.02, 1.29]) compared to patients with normal ABI after multivariable regression. Patients with elevated ABI did not demonstrate an increased risk of VTE. Conclusions: Patients with severe PAD are at higher risk for VTE than patients with normal ABI, which may be due to a multifactorial pathophysiology of profound endothelial injury as well as immobility due to claudication. Further exploration of VTE incidence in patients with severe PAD stratified by functional status is warranted to determine the optimal strategy to minimize thromboembolic morbidity and mortality in this population.

Summary: Background: Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that coexists with type 1 (T1) and 2 (T2) diabetes mellitus (DM). Little is known about comparative risk of LE and CVE in T1/T2 DM patients with PAD. Patients and methods: We queried our database of 40,144 patients ≥18 years old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated T1/T2 DM patients with PAD diagnosed by ankle brachial index (ABI; low [<1.0] or elevated [>1.4]) and retrieved demographics including glycated hemoglobin (HbA1c). Primary outcomes were LE (critical limb ischemia/vascular amputation) and CVE (myocardial infarction/ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for pertinent risk factors including age, hypertension, hyperlipidemia, smoking, and HbA1c. Results: Our study found 10,156 patients with PAD and DM (34% T1DM, 66% T2DM) with median follow-up time 34 mo (IQR 85 mo). T1DM patients were younger than T2DM (mean age 67 vs. 70 years), with higher median HbA1c (7.7 [IQR 1.9] vs. 6.7% [IQR 1.6]), and more prevalent hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use was equivocal. Elevated ABI was more common in T1DM (47 vs. 28%). LE occurred in 23% and CVE in 12% patients. LE risk was higher in T1 than T2 DM patients (HR 1.58 [95% CI 1.44, 1.73], p<0.0001), but CVE and all-cause mortality were equivocal. These observations were preserved across ABI and HbA1c subgroup analyses. Conclusions: PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for glycemic control and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed.

Introduction: Pathogenic loss-of-function variants in the RBM20 -encoded RNA-binding motif 20 splicing regulator cause a severe form of arrhythmogenic dilated cardiomyopathy (DCM). Erroneous splicing of TTN -encoded titin contributes to the pathogenesis of RBM20 -mediated disease. However, studies exploring the clinical course of RBM20 -mediated arrhythmogenic DCM alone or in comparison to TTN -mediated DCM, the most common familial cause of DCM, are lacking. Methods: The Mayo Clinic Genetic Arrhythmogenic Cardiomyopathy Registry (n=391) was used to identify all patients with a pathogenic/likely pathogenic (P/LP) variant in either RBM20 or TTN . For the purposes of this study, a ventricular arrhythmia (VA) event was defined as sudden cardiac arrest, sustained ventricular arrhythmia, or an appropriate ICD shock and an advanced heart failure (AHF) event was defined as ventricular assist device implantation or heart transplantation. Results: Overall, 40 patients with a P/LP variant in RBM20 (50% female) and 70 patients with a P/LP variant in TTN (43% female) were identified. The prevalence of a cardiac phenotype in patients with RBM20- and TTN -mediated disease was 88% and 83%, respectively. RBM20 patients were more likely to have a family history of sudden cardiac arrest (78% vs 34%; p < 0.0001) and cardiomyopathy (90% vs 61%; p=0.001). No difference in rate of ICD implantation (35% versus 33%) was observed. Interestingly, the prevalence of AHF events (10% vs 6%; p=0.5) and VA events (28% vs 24%; p=0.7) was similar between RBM20 - and TTN -positive patients. However, RBM20 patients were younger than TTN patients at the time of their event (37 ± 18 years vs 50 ± 17; p=0.0004). Time-to-event analysis showed RBM20 patients had an earlier time to AHF event (p=0.05) and time to VA event (p=0.03) than TTN patients. The mean age for AHF events was 25 years for RBM20 patients (N=4) and 47 years for TTN patients (N=4). The mean age for VA events was 29 years for RBM20 patients (N=10) and 42 years for TTN patients (N=14). Conclusions: RBM20 -mediated arrhythmogenic DCM represents a highly penetrant genetic heart disease with potentially life-threatening VAs and end stage heart failure manifestations occurring at a significantly younger age in comparison to TTN -mediated DCM.

Introduction: Myocardial inflammation likely contributes to the pathogenesis of arrhythmogenic cardiomyopathy (ACM), a clinically and genetically heterogenous disorder characterized by ventricular dysfunction and potentially life-threatening ventricular arrhythmias. Due to phenotypic overlap, some patients with genetic ACM may have been evaluated for an underlying inflammatory cardiomyopathy, namely cardiac sarcoidosis. However, the cardiac fludeoxyglucose (FDG) positron emission tomography (PET) findings in ACM patients have not been assessed systematically. Methods: All genotype-positive patients in the Mayo Clinic ACM registry who received a cardiac FDG PET were included in this study. The cardiac FDG PET scan consisted of a resting myocardial perfusion scan with N13-ammonia as well as a F18-FDG scan after a high-fat diet to suppress physiologic FDG uptake. Pertinent demographic, genetic, imaging, and outcome data were extracted from the medical record. Results: Collectively, 12 (75% female) genotype-positive ACM patients received a cardiac PET FDG scan as part of their clinical evaluation (median age at scan 45.3 years [IQR 38.9-62.1]). Amongst these patients, pathogenic/likely pathogenic variants were detected in LMNA (n=7), DSP (n=3), FLNC (n=1), and PLN (n=1). Of note, 6/12 (50%) had abnormal myocardial FDG uptake, including diffuse (entire myocardium) uptake in 2/6 (33%), focal (1-2 segments) uptake in 2/6 (33%) and patchy (3+ segments) in 2/6 (33%). Median myocardial standardized uptake value ratio was 2.1 (IQR 1.5-2.6). Interestingly, LMNA -positive patients accounted for 3 out of 6 (50%) positive studies (diffuse uptake in 2 and focal uptake in 1). Conclusion: Myocardial FDG uptake is common in genetic ACM patients undergoing cardiac FDG PET. This finding further supports the role of myocardial inflammation in genetic ACM and demonstrates the ability of cardiac FDG PET to readily detect this phenomenon. Further investigation is needed to determine (i) the role of cardiac FDG PET in the evaluation of genetic ACM, (ii) if FDG uptake in genetic ACM has prognostic value and (iii) whether the attenuation of myocardial inflammation with immunosuppressive agents can impact the clinical course of inflammatory genetic ACMs.

Introduction: Peripheral artery disease (PAD) is a risk factor for adverse limb events (LE) and cardiovascular events (CVE) that often coexists with type 1 (T1) and type 2 (T2) diabetes mellitus (DM), which differ mechanistically. There is a paucity of data on comparative risk of LE and CVE in T1DM and T2DM patients with PAD. Methods: We queried our database of 40,144 patients ≥18y old who underwent ankle brachial index (ABI) measurement from 01/1996-02/2020. We isolated patients with T1DM or T2DM and with PAD diagnosed by ABI (low [<1.0] or elevated [>1.4]). We retrieved demographics including hemoglobin A1c (A1c). Primary outcomes were LE (critical limb ischemia or vascular amputation) and CVE (myocardial infarction or ischemic stroke). All-cause mortality was a secondary outcome. Multivariable Cox proportional regression yielded hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, A1c, hypertension, hyperlipidemia, coronary artery disease (CAD), chronic kidney disease (CKD), and tobacco use. Results: Our study found 9,271 patients with PAD and DM (36% T1DM, 64% T2DM) with median follow-up time 34 mo (interquartile range [IQR] 85 mo). T1DM patients were younger than T2DM (mean age 67 vs 70y), with higher median A1c (7.7 [IQR 1.9] vs 6.7% [IQR 1.6]), and higher prevalence of hypertension, hyperlipidemia, CAD, and CKD. Antiplatelet and statin use did not differ. Elevated ABI was more common in T1DM (47 vs 27%). LE occurred in 23% and CVE in 12% of patients. LE risk was higher in T1DM patients than T2DM (HR 1.59[95% CI 1.45,1.74], p<0.0001), but CVE and all-cause mortality did not differ significantly. Conclusions: PAD patients with T1DM had a higher LE risk than those with T2DM, even after adjustment for A1c and pertinent risk factors, but CVE risk and all-cause mortality were equivocal. These data suggest a potential role for more intensive LE risk modification in PAD patients with T1DM, but further investigation is needed to minimize limb morbidity.

Summary: Background: Peripheral artery disease (PAD) impacts 3–12% of patients worldwide and is characterized by endothelial dysfunction and inflammatory pathways which are also common to venous thromboembolism (VTE), but there is a paucity of evidence regarding VTE risk in PAD patients. We investigated whether PAD is an independent risk factor for VTE. Patients and methods: We reviewed medical records of patients undergoing ABI studies at Mayo Clinic from 01/1996-02/2020. We classified patients by ABI (low [<1.0], normal [1.0–1.4], or elevated [>1.4]), as well as by specific low ABI subgroup: severely reduced (ABI: 0.00–0.39), moderately reduced (0.40–0.69), mildly reduced (0.70–0.90), and borderline reduced (0.91–0.99). The primary outcome was incident VTE event (acute lower extremity deep vein thrombosis or pulmonary embolism) after ABI measurement. Multivariable Cox proportional regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI) after adjusting for age, sex, active smoking, cancer, previous VTE, thrombophilia, anticoagulation, and revascularization. Results: 39,834 unique patients (mean age 66.3±14.3 years, median follow-up 34 months) were identified. 2,305 VTE events occurred in patients without PAD (13.0%), 2,218 in low ABI patients (13.0%), and 751 in elevated ABI patients (14.8%). After risk factor adjustment, VTE risk was modestly increased for PAD overall (HR: 1.12, 95% CI [1.06, 1.18]), including low ABI (HR: 1.11, 95% CI [1.04, 1.18]) and elevated ABI groups (HR: 1.15, 95% CI [1.04, 1.26]), compared to patients without PAD. The greatest VTE risk was in severely low ABI patients (HR: 1.46, 95% CI [1.31, 1.64]). Conclusions: In a large longitudinal cohort, we present strong clinical evidence of PAD, with low and elevated ABI, as an independent VTE risk factor, with the highest risk seen in patients with severely low ABI. Continued research is required to further investigate this relationship and its intersection with functional performance status to optimize VTE risk reduction or anticoagulation strategies in the PAD population.