A large language model-based generative natural language processing framework fine-tuned on clinical notes accurately extracts headache frequency from electronic health records.

OBJECTIVE: To develop a natural language processing (NLP) algorithm that can accurately extract headache frequency from free-text clinical notes. BACKGROUND: Headache frequency, defined as the number of days with any headache in a month (or 4 weeks), remains a key parameter in the evaluation of treatment response to migraine preventive medications. However, due to the variations and inconsistencies in documentation by clinicians, significant challenges exist to accurately extract headache frequency from the electronic health record (EHR) by traditional NLP algorithms. METHODS: This was a retrospective cross-sectional study with patients identified from two tertiary headache referral centers, Mayo Clinic Arizona and Mayo Clinic Rochester. All neurology consultation notes written by 15 specialized clinicians (11 headache specialists and 4 nurse practitioners) between 2012 and 2022 were extracted and 1915 notes were used for model fine-tuning (90%) and testing (10%). We employed four different NLP frameworks: (1) ClinicalBERT (Bidirectional Encoder Representations from Transformers) regression model, (2) Generative Pre-Trained Transformer-2 (GPT-2) Question Answering (QA) model zero-shot, (3) GPT-2 QA model few-shot training fine-tuned on clinical notes, and (4) GPT-2 generative model few-shot training fine-tuned on clinical notes to generate the answer by considering the context of included text. RESULTS: The mean (standard deviation) headache frequency of our training and testing datasets were 13.4 (10.9) and 14.4 (11.2), respectively. The GPT-2 generative model was the best-performing model with an accuracy of 0.92 (0.91, 0.93, 95% confidence interval [CI]) and R2 score of 0.89 (0.87, 0.90, 95% CI), and all GPT-2-based models outperformed the ClinicalBERT model in terms of exact matching accuracy. Although the ClinicalBERT regression model had the lowest accuracy of 0.27 (0.26, 0.28), it demonstrated a high R2 score of 0.88 (0.85, 0.89), suggesting the ClinicalBERT model can reasonably predict the headache frequency within a range of ≤ ± 3 days, and the R2 score was higher than the GPT-2 QA zero-shot model or GPT-2 QA model few-shot training fine-tuned model. CONCLUSION: We developed a robust information extraction model based on a state-of-the-art large language model, a GPT-2 generative model that can extract headache frequency from EHR free-text clinical notes with high accuracy and R2 score. It overcame several challenges related to different ways clinicians document headache frequency that were not easily achieved by traditional NLP models. We also showed that GPT-2-based frameworks outperformed ClinicalBERT in terms of accuracy in extracting headache frequency from clinical notes. To facilitate research in the field, we released the GPT-2 generative model and inference code with open-source license of community use in GitHub. Additional fine-tuning of the algorithm might be required when applied to different health-care systems for various clinical use cases.

The impact of moderate aortic stenosis in acute myocardial infarction: A multicenter retrospective study.

BACKGROUND: Aortic stenosis (AS) is associated with myocardial ischemia through different mechanisms and may impair coronary arterial flow. However, data on the impact of moderate AS in patients with acute myocardial infarction (MI) is limited. AIMS: This study aimed to investigate the impact of moderate AS in patients presenting with acute myocardial infarction (MI). METHODS: We conducted a retrospective analysis of all patients who presented with acute MI to all Mayo Clinic hospitals, using the Enterprise Mayo PCI Database from 2005 to 2016. Patients were stratified into two groups: moderate AS and mild/no AS. The primary outcome was all cause mortality. RESULTS: The moderate AS group included 183 (13.3%) patients, and the mild/no AS group included 1190 (86.7%) patients. During hospitalization, there was no difference between both groups in mortality. Patients with moderate AS had higher in-hospital congestive heart failure (CHF) (8.2% vs. 4.4%, p = 0.025) compared with mild/no AS patients. At 1-year follow-up, patients with moderate AS had higher mortality (23.9% vs. 8.1%, p < 0.001) and higher CHF hospitalization (8.3% vs. 3.7%, p = 0.028). In multivariate analysis, moderate AS was associated with higher mortality at 1-year (odds ratio 2.4, 95% confidence interval [1.4-4.1], p = 0.002). In subgroup analyses, moderate AS increased all-cause mortality in STEMI and NSTEMI patients. CONCLUSION: The presence of moderate AS in acute MI patients was associated with worse clinical outcomes during hospitalization and at 1-year follow-up. These unfavorable outcomes highlight the need for a close follow-up of these patients and for timely therapeutic strategies to best manage these coexisting conditions.

Migraine with aura associates with a higher artificial intelligence: ECG atrial fibrillation prediction model output compared to migraine without aura in both women and men.

OBJECTIVE: To compare the artificial intelligence-enabled electrocardiogram (AI-ECG) atrial fibrillation (AF) prediction model output in patients with migraine with aura (MwA) and migraine without aura (MwoA). BACKGROUND: MwA is associated with an approximately twofold risk of ischemic stroke. Longitudinal cohort studies showed that patients with MwA have a higher incidence of developing AF compared to those with MwoA. The Mayo Clinic Cardiology team developed an AI-ECG algorithm that calculates the probability of concurrent paroxysmal or impending AF in ECGs with normal sinus rhythm (NSR). METHODS: Adult patients with an MwA or MwoA diagnosis and at least one NSR ECG within the past 20 years at Mayo Clinic were identified. Patients with an ECG-confirmed diagnosis of AF were excluded. For each patient, the ECG with the highest AF prediction model output was used as the index ECG. Comparisons between MwA and MwoA were conducted in the overall group (including men and women of all ages), women only, and men only in each age range (18 to <35, 35 to <55, 55 to <75, ≥75 years), and adjusted for age, sex, and six common vascular comorbidities that increase risk for AF. RESULTS: The final analysis of our cross-sectional study included 40,002 patients (17,840 with MwA, 22,162 with MwoA). The mean (SD) age at the index ECG was 48.2 (16.0) years for MwA and 45.9 (15.0) years for MwoA (p < 0.001). The AF prediction model output was significantly higher in the MwA group compared to MwoA (mean [SD] 7.3% [15.0%] vs. 5.6% [12.4%], mean difference [95% CI] 1.7% [1.5%, 2.0%], p < 0.001). After adjusting for vascular comorbidities, the difference between MwA and MwoA remained significant in the overall group (least square means of difference [95% CI] 0.7% [0.4%, 0.9%], p < 0.001), 18 to <35 (0.4% [0.1%, 0.7%], p = 0.022), and 35 to <55 (0.5% [0.2%, 0.8%], p < 0.001), women of all ages (0.6% [0.3%, 0.8%], p < 0.001), men of all ages (1.0% [0.4%, 1.6%], p = 0.002), women 35 to <55 (0.6% [0.3%, 0.9%], p < 0.001), and men 18 to <35 (1.2% [0.3%, 2.1%], p = 0.008). CONCLUSIONS: Utilizing a novel AI-ECG algorithm on a large group of patients, we demonstrated that patients with MwA have a significantly higher AF prediction model output, implying a higher probability of concurrent paroxysmal or impending AF, compared to MwoA in both women and men. Our results suggest that MwA is an independent risk factor for AF, especially in patients <55 years old, and that AF-mediated cardioembolism may play a role in the migraine-stroke association for some patients.

National Cardiovascular Data Registry Model Predicts Long-Term Mortality in Patients Undergoing Percutaneous Coronary Interventions.

National Cardiovascular Data Registry (NCDR)-based logistic regression model is available for clinicians to predict in-hospital all-cause mortality after a percutaneous coronary intervention (PCI). However, this model has never been used to predict long-term all-cause mortality after PCI. Therefore, we sought to test the ability of the NCDR model to predict the short- and long-term risk of all-cause mortality in patients undergoing PCI. All patients undergoing PCI in the Mayo Clinic Health System were enrolled in the Mayo Clinic CathPCI registry. Patient-level demographic, clinical, and angiographic data from January 2006 to December 2017 were extracted from the registry. Patients who underwent coronary artery bypass graft surgery (CABG) were excluded. The area under the receiver operator characteristic curve (AUC) was calculated to assess the ability of the NCDR model to predict outcomes of interest (6-month, 1-year, 2-year, and 5-year all-cause mortality) after PCI. A total of 17,356 unique patients were included for the final analysis after excluding 165 patients who underwent CABG surgery. The mean age was 66.9 ± 12.5 years, and 71% were men. The 6-month, 1-year, 2-year, and 5-year all-cause mortality rates were 4.2% (n = 737), 5.8% (n = 1,005), 8.06% (n = 1,399), and 14.2% (n = 2,472), respectively. The AUCs of the NCDR model to predict 6-month, 1-year, 2-year, and 5-year all-cause mortality were 0.84 (95% CI: 0.82-0.86), 0.82 (95% CI: 0.80-0.84), 0.80 (95% CI: 0.79-0.81), and 0.78 (95% CI: 0.77-0.79), respectively. The NCDR model was able to accurately predict both short- and long-term all-cause mortality after PCI.

New pathological illuminations on 3D transillumination transesophageal echocardiography imaging.

The use of 3D technology has significantly improved the diagnostic accuracy of echocardiography by overcoming the limitation of 2D echocardiography. Transillumination 3D image post processing technique enhances shadows and contrast of cardiac structures with a movable virtual light source improving further the clarity and detail provided by conventional 3D imaging. In this report, we present 3 cases, one of mobile atherosclerotic aortic root plaque, another of small thrombi on ICD lead, and a third case of bicuspid aortic valve perforation due to infective endocarditis in whom TEE 3D transillumination further improved the diagnostic quality of conventional 3D imaging and lead to accurate clinical diagnosis.

Reversible cardiac dysfunction in severe COVID-19 infection, mechanisms and case report.

A previously healthy 49-year-old male patient presented with COVID-19 infection and required mechanical ventilation and extracorporeal membrane oxygenation due to severe hypoxemia. Echocardiography showed cardiac dysfunction with an apical sparing strain pattern, which rapidly normalized within a week. Apical sparing myocardial strain in patients with COVID-19 infection may suggest reverse-type stress cardiomyopathy.

Comparison of echocardiographic parameters with cardiac magnetic resonance imaging in the assessment of right ventricular function.

INTRODUCTION: The right ventricle (RV) strain measured by speckle tracking (RVS) is an echocardiographic parameter used to assess RV function. We compared RVS to RV fractional area change (FAC%), tricuspid annular plane systolic excursion (TAPSE) and Doppler tissue imaging-derived peak systolic velocity (S') in the assessment of right ventricular (RV) systolic function measured using cardiac magnetic resonance imaging (MRI). METHODS: We enrolled consecutive patients who underwent cardiac MRI between Jan 2012 and Dec 2017 and a transthoracic echocardiogram (TTE) within 1 month of the MRI with no interval event. Baseline clinical characteristics and MRI parameters were extracted from chart review. Echocardiographic parameters were measured prospectively. TTE parameters including RVS, TAPSE, S', and FAC% were tested for accuracy to identify impaired RV EF (EF < 45% & <30%) using receiver operator curves. RESULTS: The study cohort included 500 patients with mean age 55 years ± 18 and peak tricuspid regurgitation velocity 2.7 ± 1.4 m/s. The area under ROC for RVS was 0.69 (95% CI 0.63-0.75) and 0.78 (95% CI 0.70-0.88) to predict RVEF < 45% & RVEF < 30%, respectively. The RV FAC% had second highest accuracy of predicting RVEF among all the TTE parameters tested in study. CONCLUSION: Right ventricular strain is the most accurate echocardiographic method to detect impaired right ventricular systolic function when using MRI as the gold standard.

Quantitation of valve regurgitation severity by three-dimensional vena contracta area is superior to flow convergence method of quantitation on transesophageal echocardiography.

BACKGROUND: Quantitation of regurgitation severity using the proximal isovelocity acceleration (PISA) method to calculate effective regurgitant orifice (ERO) area has limitations. Measurement of three-dimensional (3D) vena contracta area (VCA) accurately grades mitral regurgitation (MR) severity on transthoracic echocardiography (TTE). METHODS: We evaluated 3D VCA quantitation of regurgitant jet severity using 3D transesophageal echocardiography (TEE) in 110 native mitral, aortic, and tricuspid valves and six prosthetic valves in patients with at least mild valvular regurgitation. The ASE-recommended integrative method comprising semiquantitative and quantitative assessment of valvular regurgitation was used as a reference method, including ERO area by 2D PISA for assigning severity of regurgitation grade. RESULTS: Mean age was 62.2±14.4 years; 3D VCA quantitation was feasible in 91% regurgitant valves compared to 78% by the PISA method. When both methods were feasible and in the presence of a single regurgitant jet, 3D VCA and 2D PISA were similar in differentiating assigned severity (ANOVAP<.001). In valves with multiple jets, however, 3D VCA had a better correlation to assigned severity (ANOVAP<.0001). The agreement of 2D PISA and 3D VCA with the integrative method was 47% and 58% for moderate and 65% and 88% for severe regurgitation, respectively. CONCLUSION: Measurement of 3D VCA by TEE is superior to the 2D PISA method in determination of regurgitation severity in multiple native and prosthetic valves.

Role of lipoprotein(a) concentrations in bioprosthetic aortic valve degeneration.

OBJECTIVES: Lipoprotein(a) (Lp(a)) is associated with an increased incidence of native aortic stenosis, which shares similar pathological mechanisms with bioprosthetic aortic valve (bAV) degeneration. However, evidence regarding the role of Lp(a) concentrations in bAV degeneration is lacking. This study aims to evaluate the association between Lp(a) concentrations and bAV degeneration. METHODS: In this retrospective multicentre study, patients who underwent a bAV replacement between 1 January 2010 and 31 December 2020 and had a Lp(a) measurement were included. Echocardiography follow-up was performed to determine the presence of bioprosthetic valve degeneration, which was defined as an increase >10 mm Hg in mean gradient from baseline with concomitant decrease in effective orifice area and Doppler Velocity Index, or new moderate/severe prosthetic regurgitation. Levels of Lp(a) were compared between patients with and without degeneration and Cox regression analysis was performed to investigate the association between Lp(a) levels and bioprosthetic valve degeneration. RESULTS: In total, 210 cases were included (mean age 74.1±9.4 years, 72.4% males). Median time between baseline and follow-up echocardiography was 4.4 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.7%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in patients affected by degeneration versus non-affected cases: 50.0 (IQR 72.0) vs 15.6 (IQR 48.6) mg/dL, p=0.002. In the regression analysis, high Lp(a) levels (≥30 mg/dL) were associated with degeneration both in a univariable analysis (HR 3.6, 95% CI 1.7 to 7.6, p=0.001) and multivariable analysis adjusted by other risk factors for bioprostheses degeneration (HR 4.4, 95% CI 1.9 to 10.4, p=0.001). CONCLUSIONS: High serum Lp(a) is associated with bAV degeneration. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) levels could slow bioprostheses degradation.

Echocardiography-Based Deep Learning Model to Differentiate Constrictive Pericarditis and Restrictive Cardiomyopathy.

BACKGROUND: Constrictive pericarditis (CP) is an uncommon but reversible cause of diastolic heart failure if appropriately identified and treated. However, its diagnosis remains a challenge for clinicians. Artificial intelligence may enhance the identification of CP. OBJECTIVES: The authors proposed a deep learning approach based on transthoracic echocardiography to differentiate CP from restrictive cardiomyopathy. METHODS: Patients with a confirmed diagnosis of CP and cardiac amyloidosis (CA) (as the representative disease of restrictive cardiomyopathy) at Mayo Clinic Rochester from January 2003 to December 2021 were identified to extract baseline demographics. The apical 4-chamber view from transthoracic echocardiography studies was used as input data. The patients were split into a 60:20:20 ratio for training, validation, and held-out test sets of the ResNet50 deep learning model. The model performance (differentiating CP and CA) was evaluated in the test set with the area under the curve. GradCAM was used for model interpretation. RESULTS: A total of 381 patients were identified, including 184 (48.3%) CP, and 197 (51.7%) CA cases. The mean age was 68.7 ± 11.4 years, and 72.8% were male. ResNet50 had a performance with an area under the curve of 0.97 to differentiate the 2-class classification task (CP vs CA). The GradCAM heatmap showed activation around the ventricular septal area. CONCLUSIONS: With a standard apical 4-chamber view, our artificial intelligence model provides a platform to facilitate the detection of CP, allowing for improved workflow efficiency and prompt referral for more advanced evaluation and intervention of CP.

Efficacy of Sacubitril-Valsartan on Survival and Cardiac Remodeling in Hypotensive Heart Failure With Reduced Ejection Fraction: A Multicenter Study.

OBJECTIVE: To investigate whether hypotensive patients diagnosed with heart failure and reduced ejection fraction (HFrEF) might benefit from angiotensin receptor-neprilysin inhibitors (ARNis) in real-world practice because patients with baseline systolic blood pressure (SBP) of less than 100 mm Hg have been excluded from landmark trials. PATIENTS AND METHODS: In this multicenter study conducted between January 1, 2013, and December 31, 2021, a total of 7562 symptomatic patients with HFrEF were enrolled and grouped by SBP (hypotension was defined as an SBP of less than 100 mm Hg) and ARNi use as follows: group 1, hypotensive/non-ARNi users (n=484); group 2, hypotensive/ARNi users (n=308); group 3, nonhypotensive/non-ARNi users (n=4560); and group 4, nonhypotensive/ARNi users (n=2210). Inverse probability of treatment weighting was used to balance baseline characteristics for survival analysis. RESULTS: Diverse baseline characteristics and lower rates of medication use were found among non-ARNi users compared with ARNi users. Hypotensive/ARNi users had lower ARNi initiation doses than nonhypotensive/ARNi users. We observed significantly lower mortality, composite heart failure hospitalization, and CV death for hypotensive/ARNi and the other 2 nonhypotensive groups (groups 3 and 4) during a median follow-up of 3.43 years (all P<.05), with a similar effect on reverse remodeling for the hypotensive/ARNi group compared with the hypotensive/non-ARNi group. The event-free survival benefits of ARNi vs renin-angiotensin system inhibitors were consistent with the lower boundary of SBP for clinical benefits found until 88 mm Hg (spline curves) after inverse probability of treatment weighting. CONCLUSION: Patients with HFrEF and hypotension may still benefit from ARNi treatment. Patients with hypotensive HFrEF should not be routinely excluded from ARNi use in a real-world setting.

Disproportionately High Aortic Valve Calcium Scores in Atrial Fibrillation: Implications for Transcatheter Aortic Valve Replacement.

AIMS: Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR), potentially delaying intervention in AF. This study compared outcomes in patients with AF and SR following transcatheter aortic valve replacement (TAVR) and investigated delay in TAVR based on computed tomography aortic valve calcium score (AVCS). METHODS AND RESULTS: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. Baseline characteristics and overall survival were compared between those in SR and AF. There were 820 patients (mean age 81 years; 41.6% female) included. AF was present in 356 patients. Patients in AF were older (82.2 vs. 80.5, p = 0.003), had lower MG compared to SR patients (42.0 vs. 44.9, p = 0.002) with similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Median AVCS was higher in AF (males: AF 2850.0 vs. SR 2561.0, p = 0.044; females: AF 1942.0 vs. SR 1610.5, p = 0.025). Projected AVCS assuming same age of diagnosis was similar between AF and SR. Median survival post-TAVR was worse in AF compared to SR (3.2 vs 5.4 years, log rank p < 0.001). AF, lower MG, higher RVSP, dialysis, diabetes, and significant TR were associated with higher mortality (p < 0.05 for all). CONCLUSION: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at TAVR referral.

Association between echocardiographic velocity time integral ratio of mitral valve and left ventricular outflow tract and clinical outcomes post transcatheter edge-to-edge mitral valve repair.

Background: Residual mitral regurgitation (MR) is frequent after transcatheter edge-to-edge repair (TEER). There is controversy regarding the clinical impact of residual MR and its quantitative assessment by transthoracic echocardiography (TTE), which is often challenging with multiple eccentric jets and artifact from the clip. The utility of the velocity time integral (VTI) ratio between the mitral valve (MV) and left ventricular outflow tract (LVOT), (VTIMV/LVOT), a simple Doppler measurement that increases with MR, has not been assessed post TEER. Methods: Baseline characteristics, clinical outcomes, and TTE data from patients who underwent TEER between 2014 and 2021 across three academic centers were retrospectively analyzed. Post-procedure TTEs were evaluated for VTIMV/LVOT in the first three months after TEER. One-year outcomes including all-cause and cardiac mortality, major adverse cardiac events, and MV reintervention were compared between patients with high VTIMV/LVOT (≥2.5) and low (<2.5). Results: In total, 372 patients were included (mean age 78.7 ± 8.8 years, 68 % male, mean pre-TEER ejection fraction of 50.5 ± 14.7 %). Follow up TTEs were performed at a median of 37.5 (IQR 30-48) days post-procedure. Patients with high VTIMV/LVOT had significantly higher all-cause mortality (HR 2.10, p = 0.003), cardiac mortality (HR 3.03, p = 0.004) and heart failure admissions (HR 2.28, p < 0.001) at one-year post-procedure. There was no association between raised VTIMV/LVOT and subsequent MV reintervention. Conclusion: High VTIMV/LVOT has clinically significant prognostic value at one year post TEER. This tool could be used to select patients for consideration of repeat intervention.

Opportunistic screening for coronary artery calcium deposition using chest radiographs - a multi-objective models with multi-modal data fusion.

Background: To create an opportunistic screening strategy by multitask deep learning methods to stratify prediction for coronary artery calcium (CAC) and associated cardiovascular risk with frontal chest x-rays (CXR) and minimal data from electronic health records (EHR). Methods: In this retrospective study, 2,121 patients with available computed tomography (CT) scans and corresponding CXR images were collected internally (Mayo Enterprise) with calculated CAC scores binned into 3 categories (0, 1-99, and 100+) as ground truths for model training. Results from the internal training were tested on multiple external datasets (domestic (EUH) and foreign (VGHTPE)) with significant racial and ethnic differences and classification performance was compared. Findings: Classification performance between 0, 1-99, and 100+ CAC scores performed moderately on both the internal test and external datasets, reaching average f1-score of 0.66 for Mayo, 0.62 for EUH and 0.61 for VGHTPE. For the clinically relevant binary task of 0 vs 400+ CAC classification, the performance of our model on the internal test and external datasets reached an average AUCROC of 0.84. Interpretation: The fusion model trained on CXR performed better (0.84 average AUROC on internal and external dataset) than existing state-of-the-art models on predicting CAC scores only on internal (0.73 AUROC), with robust performance on external datasets. Thus, our proposed model may be used as a robust, first-pass opportunistic screening method for cardiovascular risk from regular chest radiographs. For community use, trained model and the inference code can be downloaded with an academic open-source license from https://github.com/jeong-jasonji/MTL_CAC_classification . Funding: The study was partially supported by National Institute of Health 1R01HL155410-01A1 award.

Role of Genetics in Diagnosis and Management of Hypertrophic Cardiomyopathy: A Glimpse into the Future.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiomyopathy. It follows an autosomal dominant inheritance pattern in most cases, with incomplete penetrance and heterogeneity. It is familial in 60% of cases and most of these are caused by pathogenic variants in the core sarcomeric genes (MYH7, MYBPC3, TNNT2, TNNI3, MYL2, MYL3, TPM1, ACTC1). Genetic testing using targeted disease-specific panels that utilize next-generation sequencing (NGS) and include sarcomeric genes with the strongest evidence of association and syndrome-associated genes is highly recommended for every HCM patient to confirm the diagnosis, identify the molecular etiology, and guide screening and management. The yield of genetic testing for a disease-causing variant is 30% in sporadic cases and up to 60% in familial cases and in younger patients with typical asymmetrical septal hypertrophy. Genetic testing remains challenging in the interpretation of results and classification of variants. Therefore, in 2015 the American College of Medical Genetics and Genomics (ACMG) established guidelines to classify and interpret the variants with an emphasis on the necessity of periodic reassessment of variant classification as genetic knowledge rapidly expands. The current guidelines recommend focused cascade genetic testing regardless of age in phenotype-negative first-degree relatives if a variant with decisive evidence of pathogenicity has been identified in the proband. Genetic test results in family members guide longitudinal clinical surveillance. At present, there is emerging evidence for genetic test application in risk stratification and management but its implementation into clinical practice needs further study. Promising fields such as gene therapy and implementation of artificial intelligence in the diagnosis of HCM are emerging and paving the way for more effective screening and management, but many challenges and obstacles need to be overcome before establishing the practical implications of these new methods.

The prognostic value of artificial intelligence to predict cardiac amyloidosis in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement.

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.

Lipoprotein(a) and Long-term In-stent Restenosis after Percutaneous Coronary Intervention.

AIM: Lipoprotein(a) [Lp(a)] has demonstrated its association with atherosclerosis and myocardial infarction. However, its role in the development of in-stent restenosis (ISR) after percutaneous coronary intervention (PCI) is not clearly established. The aim of this study is to investigate the association between Lp(a) and ISR. METHODS: A retrospective study of adult patients who underwent successful PCI between January 2006 and December 2017 at the three Mayo Clinic sites and had a preprocedural Lp(a) measurement was conducted. Patients were divided into two groups according to the serum Lp(a) concentration (high Lp(a) ≥50 mg/dl and low Lp(a) <50 mg/dl). Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) versus those with low Lp(a). RESULTS: A total of 1209 patients were included, with mean age 65.9 ±11.7 years and 71.8% were male. Median follow-up after baseline PCI was 8.8 (IQR 7.4) years. Restenosis was observed in 162 (13.4%) patients. Median serum levels of Lp(a) were significantly higher in patients affected by ISR versus non-affected cases: 27 (IQR 73.8) vs. 20 (IQR 57.5) mg/dL, p=0.008. The rate of ISR was significantly higher among patients with high Lp(a) versus patients with low Lp(a) values (17.0% vs 11.6%, p=0.010). High Lp(a) values were independently associated with ISR events (HR 1.67, 95%CI 1.18 to 2.37, p=0.004), and this association was more prominent after the first year following the PCI. CONCLUSION: Lipoprotein(a) is an independent predictor for long-term in-stent restenosis and should be considered in the evaluation of patients undergoing PCI.

The role of Lp(a) in the development of in-stent restenosis is not clearly established. In this study including 1209 patients who underwent successful percutaneous coronary intervention and had a preprocedural Lp(a) measurement between 2006 and 2017, the rates of restenosis were significantly higher among patients with high Lp(a) versus patients with low Lp(a) values and high Lp(a) concentrations were independently associated with restenosis events. Lp(a) should be considered as a risk factor for long term in-stent restenosis in the evaluation of patients undergoing percutaneous coronary intervention and assessed as a potential therapeutic target for reducing residual cardiovascular risk in this population.

Identifying the Causes of Unexplained Dyspnea at High Altitude Using Normobaric Hypoxia with Echocardiography.

Exposure to high altitude results in hypobaric hypoxia, leading to physiological changes in the cardiovascular system that may result in limiting symptoms, including dyspnea, fatigue, and exercise intolerance. However, it is still unclear why some patients are more susceptible to high-altitude symptoms than others. Hypoxic simulation testing (HST) simulates changes in physiology that occur at a specific altitude by asking the patients to breathe a mixture of gases with decreased oxygen content. This study aimed to determine whether the use of transthoracic echocardiography (TTE) during HST can detect the rise in right-sided pressures and the impact of hypoxia on right ventricle (RV) hemodynamics and right to left shunts, thus revealing the underlying causes of high-altitude signs and symptoms. A retrospective study was performed including consecutive patients with unexplained dyspnea at high altitude. HSTs were performed by administrating reduced FiO2 to simulate altitude levels specific to patients' history. Echocardiography images were obtained at baseline and during hypoxia. The study included 27 patients, with a mean age of 65 years, 14 patients (51.9%) were female. RV systolic pressure increased at peak hypoxia, while RV systolic function declined as shown by a significant decrease in the tricuspid annular plane systolic excursion (TAPSE), the maximum velocity achieved by the lateral tricuspid annulus during systole (S' wave), and the RV free wall longitudinal strain. Additionally, right-to-left shunt was present in 19 (70.4%) patients as identified by bubble contrast injections. Among these, the severity of the shunt increased at peak hypoxia in eight cases (42.1%), and the shunt was only evident during hypoxia in seven patients (36.8%). In conclusion, the use of TTE during HST provides valuable information by revealing the presence of symptomatic, sustained shunts and confirming the decline in RV hemodynamics, thus potentially explaining dyspnea at high altitude. Further studies are needed to establish the optimal clinical role of this physiologic method.

Cardiac Allograft Vasculopathy: Challenges and Advances in Invasive and Non-Invasive Diagnostic Modalities.

Cardiac allograft vasculopathy (CAV) is a distinct form of coronary artery disease that represents a major cause of death beyond the first year after heart transplantation. The pathophysiology of CAV is still not completely elucidated; it involves progressive circumferential wall thickening of both the epicardial and intramyocardial coronary arteries. Coronary angiography is still considered the gold-standard test for the diagnosis of CAV, and intravascular ultrasound (IVUS) can detect early intimal thickening with improved sensitivity. However, these tests are invasive and are unable to visualize and evaluate coronary microcirculation. Increasing evidence for non-invasive surveillance techniques assessing both epicardial and microvascular components of CAV may help improve early detection. These include computed tomography coronary angiography (CTCA), single-photon emission computed tomography (SPECT), positron emission tomography (PET), and vasodilator stress myocardial contrast echocardiography perfusion imaging. This review summarizes the current state of diagnostic modalities and their utility and prognostic value for CAV and also evaluates emerging tools that may improve the early detection of this complex disease.