Barry, Timothy

Background: A key determinant of prognosis in pulmonary hypertension (PH) is the right ventricle’s (RV) ability to adapt to increased pulmonary vascular resistance. Consequently, markers of RV-pulmonary artery (PA) coupling may improve prognostic prediction in PH. The ratio of tricuspid annular plane systolic excursion (TAPSE) to systolic PA pressure (sPAP) has been proposed as a surrogate for RV-PA coupling and a reliable prognostic marker, however, the existing data on the prognostic value of the ratio between RV longitudinal strain (RVLS) and sPAP as a surrogate for RV-PA coupling is scarce. Hypothesis: To evaluate the prognostic role of RVLS/RVSP in PH patients and to compare this novel marker with established markers of RV-PA coupling. Methods: This is a single-center study that included adult patients with PH classified as group I or IV, all of whom had undergone a transthoracic echocardiogram (TTE) within one year prior to the initiation of PH-specific treatment. Certified sonographers procured RV strain measurements using a specific software (Epsilon Imaging, Ann Arbor, MI). Receiver operating characteristic (ROC) analysis was used to determine the best cutoff for predicting all-cause mortality at one-year for RVLS/RVSP and TAPSE/RVSP. The association of RVLS/RVSP and TAPSE/RVSP with mortality at one year was assessed using the Kaplan-Meier analysis and multivariate Cox regression analysis (adjusted for REVEAL LITE 2.0 risk score). Results: A total of 160 patients were included with a median age of 67.2 (56.8, 73.7) years and 47 (29.2%) were male . ROC analysis revealed optimal cutoffs of 0.265 (AUC = 0.83) for RVLS/RVSP and 0.185 (AUC = 0.77) for TAPSE/RVSP to predict all-cause mortality at one year. One-year cumulative incidence of all-cause mortality was lower among patients with RVLS/RVSP ≥ 0.265 (0 % vs 13.7 %, p = 0.001) and patients with TAPSE/RVSP ≥ 0.185 (1.8 % vs 16.7 %, p = 0.001) (Figure 1) . In the multivariate analysis, RVLS/RVSP < 0.265 was associated with higher risk of mortality at one year (HR: 2.38, 95 % CI: 1.05 to 5.38, p = 0.036) while TAPSE/RVSP < 0.185 was not (HR: 2.01, 95 % CI: 0.93 to 4.31, p = 0.072). Conclusions: RVLS/ RVSP may be a valuable prognostic marker in PH patients and could outperform conventional TTE parameters as a surrogate for detecting RV-PA coupling.

Abstract Background/Introduction Access to timely healthcare in disadvantaged areas remains essential to achieving equitable health outcomes, especially in regions facing structural and social vulnerabilities. Purpose To assess wait times for cardiovascular disease consultations in US-Mexico border regions compared to non-border regions among US Veterans. Methods This cross-sectional analysis included all veteran cardiovascular consultations referred through the Veterans Choice Program to community healthcare centers from 2014 to 2020. We obtained the average wait times in days for consultation approval, scheduling, completion, and total wait time from approval to consultation completion. All consultations were classified by county of residence as either within a US-Mexico border region or a non-border region, as per the La Paz Agreement. Multivariable linear regression analyses were performed to evaluate the impact of border status on average wait times. ARIMA modeling was completed to estimate forecasted wait times during the COVID-19 pandemic. Results A total of 485,158 consultations related to outpatient cardiovascular disease were retrieved from the VA Healthcare System. Amongst these, 461,696 of the consultations were placed in non-border regions whereas 23,462 consultations were placed in US-Mexico border regions. The most common consultation requests were made for general cardiology clinic (n=365,227), echocardiography (n=32,017), cardio-pulmonary rehabilitation (n=40,699), and cardiac stress testing (n=16,258). Wait times for cardiovascular disease consultations were not higher in US-Mexico border counties than in non-border regions. For electrophysiology consultations specifically, border counties exhibited significantly shorter total wait times (coeff = -10.81, p=0.008). Additionally, while the COVID-19 pandemic led to increased total wait times in non-border areas (Figure 1), total wait times in border regions remained stable during this period (Figure 2). Conclusions Our findings suggest that US-Mexico border region status does not result in longer wait times for cardiovascular disease consultations, with the exception of shorter wait times for electrophysiology services. This study provides important insights into the unique dynamics of healthcare access in structurally disadvantaged regions, highlighting that wait times are not a significant barrier to cardiovascular care in border areas, and emphasizes the need to consider regional differences in healthcare delivery policies.

Abstract Background Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) have emerged as a vital component in the management of heart failure (HF), demonstrating significant improvements in cardiac function. However, their impact on outcomes in patients with acute myocardial infarction (AMI) remains poorly characterized. This study aimed to evaluate the long-term outcomes of SGLT2-Is among patients with AMI. Methods We conducted a retrospective cohort study using data from the TriNetX Banner Health Network platform in the United States, including patients aged ≥18 years with AMI identified through ICD-10 codes. Patients were categorized into two cohorts based on SGLT2-I use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities (e.g., hypertension, diabetes, chronic kidney disease, heart failure, and hyperlipidemia), and medication use (e.g., heart failure therapies, antiplatelet agents, anticoagulants). Risk ratios (RRs) and 95% confidence intervals (95% CIs) were estimated for the following cardiovascular outcomes: acute HF hospitalizations, stroke, all-cause hospitalizations, recurrent AMI, cardiac arrest, and new-onset atrial fibrillation (AF). Kaplan-Meier analysis was completed to estimate survival probability from all-cause hospitalizations. Results After PSM, 2,440 patients were analyzed (1,220 SGLT2-I users; 1,220 non-users). Both cohorts had similar characteristics without any residual imbalance: mean age 67.7 years in the SGLT2-I group vs. 67.5 years in non-users, and both groups included 85.2% White and 33.6% female patients. Mean follow-up duration was 608 days for SGLT2-I users and 1,013.5 days for non-users. SGLT2-I use was associated with significantly lower rates of all-cause hospitalizations (RR: 0.712; 95% CI: 0.652–0.777), HF-related hospitalizations (RR: 0.878; 95% CI: 0.781–0.987), recurrent AMI (RR: 0.821; 95% CI: 0.703–0.959), and cardiac arrest (RR: 0.500; 95% CI: 0.345–0.725). No significant differences were observed in stroke (RR: 0.909; 95% CI: 0.702–1.178) or new-onset AF (RR: 0.889; 95% CI: 0.782–1.010) between the cohorts. Conclusions SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in all-cause and HF-related hospitalizations, recurrent AMI, and cardiac arrest. While these findings are hypothesis-generating, they emphasize the need for prospective clinical trials to confirm these results.Kaplan-Meier Analysis.

Abstract Aims Sodium-glucose cotransporter 2 inhibitors (SGLT2-Is) improve heart failure (HF) outcomes but their effects on acute myocardial infarction (AMI) remain poorly characterized. This study aimed to evaluate the 1-year cardiovascular outcomes of SGLT2-Is among patients with AMI. Methods and results We conducted an observational, retrospective cohort study using TriNetX data, including patients aged ≥18 with AMI identified via ICD-10 codes regardless of left ventricular ejection fraction (LVEF), categorized by SGLT2-Is use. Propensity score matching (PSM) was performed to balance baseline demographics, comorbidities, and medication use. Adjusted odds ratios (aORs) were estimated for the primary outcome (recurrent AMI) and the secondary outcomes (acute HF hospitalizations, stroke, all-cause hospitalizations, all-cause mortality, new-onset atrial fibrillation, and cardiac arrest). After PSM, 89 554 patients were analysed (44 777 SGLT2-Is users; 44 777 non-users). The mean age was ∼68 years in both cohorts with a similarly high burden of cardiovascular comorbidities. Mean follow-up duration was 290.854 days for SGLT2-Is users and 284.465 days for non-users. SGLT2-Is use was linked to lower rates of recurrent AMI [aOR: 0.459; 95% confidence interval (CI): 0.367–0.551], all-cause hospitalizations (aOR: 0.782; 95% CI: 0.762–0.803), all-cause mortality (aOR: 0.640; 95% CI: 0.612–0.670), and cardiac arrest (aOR: 0.834; 95% CI: 0.773–0.900). No differences were observed in acute HF hospitalizations, new-onset atrial fibrillation, or stroke. Conclusion SGLT2-Is are associated with improved cardiovascular outcomes in patients with AMI, including reductions in recurrent AMI, all-cause hospitalizations and mortality, and cardiac arrest. These findings emphasize the need for prospective clinical trials involving patients with AMI and other cardiovascular comorbidities, regardless of LVEF, to confirm these results.

Abstract Aims Atrial fibrillation (AF) is the most common cardiac arrhythmia. Although lipoprotein(a) [Lp(a)] is known to be a well-established risk factor for atherosclerotic cardiovascular disease, its role in the development of AF, independent of this association, remains unclear. Methods and results Adult patients from the three Mayo Clinic sites with a baseline Lp(a) and without AF history were included. Patients were categorized into two groups based on their Lp(a) levels: high Lp(a) (≥50 mg/dL) and low Lp(a) (&lt;50 mg/dL). Survival probabilities free from incident AF were compared between Lp(a) groups, during a follow-up period up to 15 years, using the Kaplan–Meier curve and the log-rank test. Multivariable Cox regression analysis was also conducted. A total of 75 376 patients were included (median age: 55 years, 59% males), with a median follow-up duration of 8.8 (inter-quartile range: 3.4, 14.8) years. Incident AF was detected in 5738 (7.6%) patients. Survival probability free from incident AF was significantly lower in patients with elevated Lp(a) (86%) compared with those with low Lp(a) (88%, log-rank P &lt; 0.001). Multivariable analysis adjusted for potential risk factors of AF showed a statistically significant association of elevated Lp(a) with an 11% increase in AF risk (adjusted hazard ratio: 1.11, 95% confidence interval: 1.05–1.18). Conclusion Our study suggests that elevated Lp(a) (≥50 mg/dL) is an independent risk factor for incident AF. Future prospective studies are warranted to validate our results and to test if reducing Lp(a) could mitigate the burden of AF.

Abstract Aims 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 and results 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) &lt; 50 mg/dL]. Univariable and multivariable analyses were performed to compare risk of ISR between patients with high Lp(a) vs. those with low Lp(a). 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 [interquartile range (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 vs. 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) vs. patients with low Lp(a) values (17.0% vs. 11.6%, P = 0.010). High Lp(a) values were independently associated with ISR events (hazard ratio 1.67, 95% confidence interval 1.18–2.37, 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 ISR and should be considered in the evaluation of patients undergoing PCI.

Abstract Background Bicuspid aortic valve (BAv) is associated with increased oxidative stress and inflammation, resulting in valve fibrosis, calcification, and ultimately early degenerative valve disease, often necessitating premature aortic valve intervention. In recent years, growing evidence has been published supporting the role of lipoprotein(a) [Lp(a)], an important carrier of oxidized phospholipids, in the development of aortic valve disease in the general population. However, the specific influence of Lp(a) levels in patients with BAv remains to be firmly established. Purpose To assess the role of Lp(a) levels in the development of aortic valve disease and the necessity for aortic valve interventions among individuals with BAv. Methods This retrospective multicenter study encompassed consecutive patients diagnosed with BAv from January 1997 to December 2022, all of whom had undergone serum Lp(a) measurement. This study evaluated the association between Lp(a) concentrations and the occurrence of aortic valve interventions. A cutoff point of ≥30 mg/dl for high Lp(a) levels was established. Binary logistic regression was utilized to calculate the odds ratio (OR) for an aortic intervention according to high versus low Lp(a) levels. Additionally, Kaplan Meier curves were employed to estimate the cumulative requirement for an aortic valve replacement based on Lp(a) concentrations. Results A total of 452 patients with BAv and a Lp(a) measurement were included in the study, with a mean age of 37.2 ±10.5 years at the time of BAv diagnosis, with 71.2% being male. Among these, 101 (22.3%) patients underwent an aortic valve replacement. In 72 cases (71.3%) aortic stenosis was the primary indication for intervention, while aortic regurgitation accounted for 29 cases (28.7%). The presence of elevated Lp(a) levels (≥30 mg/dl) demonstrated a significant association with the requirement for an aortic valve intervention (OR 2.2, 95%CI 1.4-3.6, p&lt;0.001) in both the regression analysis and using the Kaplan-Meier estimator (Figure). High Lp(a) concentrations posed a risk factor for aortic valve replacements regardless of whether the primary indication for intervention was significant stenosis (OR 1.8, 95%CI 1.1-3.1, p=0.028) or regurgitation (OR 2.5, 95%CI 1.2-5.4, p=0.018). Conclusion Increased concentrations of Lp(a) may influence the clinical trajectory of patients with a BAv and may be a significant risk factor for aortic valve replacement, irrespective of the primary indication for intervention. Further investigations will be critical in unveiling the precise pathological mechanisms of Lp(a) in BAv. Confirming whether reducing Lp(a) levels could slow the progression of aortic disease in this demographic requires further exploration. Kaplan-Meier estimator.

Abstract Introduction Lipoprotein(a) [Lp(a)] is associated with an increased incidence of aortic stenosis. Bioprosthetic aortic valve degeneration and native aortic stenosis share similar pathological mechanisms. Evidence regarding the role of serum Lp(a) concentrations in bioprosthetic aortic valve degeneration is lacking. Purpose To evaluate the association between serum Lp(a) concentrations and bioprosthetic aortic valve degeneration. Methods In this retrospective multicenter study, consecutive patients who underwent a bioprosthetic aortic valve replacement between Jan-2010 and Dec-2020 and had a preoperatory serum Lp(a) measurement were included. A baseline transthoracic echocardiography (TTE) was performed following the aortic valve replacement and a follow-up TTE was performed at least 24 months after the baseline study to determine the presence of bioprosthetic valve degeneration. Significant degeneration was defined as: (a) an increase &gt;10 mmHg in mean bioprosthetic aortic valve gradient from baseline status + a decrease in effective orifice area + a decrease in Doppler velocity index + exclusion of clinically thrombotic leaflet thickening, OR (b) new moderate or severe prosthetic aortic regurgitation (if the main component was periprosthetic, then it was not considered). Lp(a) concentrations were compared between patients with and without degeneration and regression analysis was conducted to investigate the association between bioprosthetic valve degeneration and Lp(a) levels. Results In total, 211 cases were included (mean age 74.1 ±9.4 years, 72.0% males, 29.9% transcatheter aortic valve replacements) (Figure 1). Median time between baseline and follow-up TTE was 5.0 (IQR 3.7) years. Bioprostheses degeneration was observed in 33 (15.6%) patients at follow-up. Median serum levels of Lp(a) were significantly higher in the patients affected by degeneration versus non-affected cases (50.0 vs 15.7 mg/dl, p=0.003). In the regression analysis, high Lp(a) levels (≥30 mg/dl) were associated with degeneration both in a univariate analysis (OR 4.8, 95%CI 2.2-10.9, p&lt;0.001) and multivariate analysis adjusted by other risk factors for bioprostheses degeneration (age, sex, hypertension, smoking, patient prosthesis mismatch, creatinine levels, and body surface area) (OR 5.2, 95%CI 2.1-12.8, p&lt;0.001). Conclusion Serum Lp(a) concentrations seem to be a risk factor for bioprosthetic aortic valve degeneration (Figure 2). There is an increasing need to accurately predict bioprosthetic aortic valve degeneration and to develop novel methods and treatments to increase their durability. Prospective studies are needed to confirm these findings and to investigate whether lowering Lp(a) could slow bioprostheses degradation.Population characteristicsLp(a) and bioprostheses degeneration

Abstract Funding Acknowledgements Type of funding sources: Private hospital(s). Main funding source(s): Mayo Clinic Background/Introduction Syncope is a common presentation in heart failure (HF) patients. However, the associations between syncope and prognosis in HF patients with the cardiac implantable electronic device (CIED) have not been demonstrated. It is unclear whether syncope increases all-cause mortality in HF patients with CIED. Purpose We aimed to examine the association between syncope and all-cause mortality in the largest cohort of HF with reduced ejection fraction (HFrEF), mid-ranged ejection fraction (HFmEF), and preserved ejection fraction (HFpEF) patients with and without CIED. Methods A retrospective cohort of patients with HF and syncope at our hospital between 2010 and 2015 were identified, and 1:1 propensity was matched with a control group of HF patients without syncope. A chart review was conducted. The multivariate Cox regression model was applied to estimate the association between syncope and the all-cause mortality endpoint. Results 3,449 HF patients were diagnosed with syncope (mean age, 72.8±14.5 years; 41.5% women), and the propensity-matched control HF patients without syncope (n=3,449) aged 72.8±14.3 years, and 42.5% women were selected. Cardiac implantable electronic devices were implanted more in HF patients with syncope (32.5% versus 13.7%, p&lt;0.001). Implantable cardioverter defibrillators were implanted more in HF patients with syncope (15.6% versus 8.3%, p&lt;0.001) as well as pacemakers (16.9% versus 7.5%, p&lt;0.001) and cardiac resynchronization therapy devices (6.9% versus 4.8%, p=0.015). Among HF patients with CIED, syncope significantly increased the risk of all-cause mortality in HFrEF patients (hazard ratio [HR]=1.479, 95% confidence interval [CI]: 1.197-1.828, p&lt;0.001) but not in HFpEF (HR=0.980, 95%CI: 0.793-1.210, p=0.849)(Figure 1). Syncope also tended to increase the risk of all-cause mortality in HFmEF patients with CIED but was not significant (HR=1.193, 95%CI: 0.762-1.865, p=0.762)(Figure 1). Among HF patients without CIED, syncope did not increase the risk of all-cause mortality in HFrEF (HR=0.923, 95%CI: 0.806-1.057, p=0.247), HFmEF (HR=1.074, 95%CI: 0.848-1.360, p=0.554), or HFpEF (HR=0.964, 95%CI: 0.883-1.052, p=0.406). Conclusions Syncope significantly increased the risk of all-cause mortality in HFrEF patients but not in HFmEF or HFpEF patients with CIED. The association of syncope and increased mortality in HFrEF patients with CIED suggests that syncope may be a marker and a factor of mortality and warrants further investigation.

Abstract Funding Acknowledgements Type of funding sources: None. Background/Introduction Immune checkpoint inhibitor (ICI) myocarditis is a life-threatening condition characterized by lymphocytic myocardial infiltration[1]. Complete heart block (CHB) occurs in 15% of cases and is often fatal[2-4]. The nature and optimal management of this often-malignant condition is poorly understood[5]. Purpose This case series assesses prognostic factors associated with survival at 90 days among people with ICI myocarditis and CHB. Methods The electronic patient record system was used to identify patients admitted with ICI myocarditis. A two-physician review was used to assess the presence of ICI-associated CHB. Wilcoxon rank sum and Spearman’s rank correlation were used for categorical and quantitative variables respectively. Data was analysed using STATA/IC 16.1. The primary outcome was person-day survival 90 days after presenting symptom onset. Results Six patients were included in the final analysis. Mean survival was 47 person days. All had metastatic disease and presented 15 to 32 days after the first ICI infusion. All had muscle weakness. Other common self-symptoms were shortness of breath (4), blurred vision (4), double vision (3), collapse (3), and leg swelling (1). Proximal myopathy (2), fatigable myopathy (1), ptosis (3), and peripheral oedema (1) were present on examination. Raised troponin T and white blood cell count (WBC) were associated with 90-day survival (see Table 1). Nt-pro BNP, AST, and CK levels were raised in all patients. Two patients were tested for anti-striated muscle antibody titres, and both were strongly positive. Increase in QRS duration compared to baseline ECG was associated with lower survival at 90 days. Only one patient had CHB on admission. Steroid dose, IVIG, and plasmapheresis weren’t associated with survival. One patient declined device therapy. One declined permanent pacemaker (PPM) after insertion of transvenous pacemaker (TVP). Both died within 2 weeks. Three people underwent insertion of a transvenous pacemaker (TVP) followed by PPM insertion (table 2). All three eventually died within 100 days. One person received isoproterenol and immunosuppression as a bridge to PPM and survived. One patient was managed initially with TVP but subsequently declined PPM insertion. TVP removal resulted in CHB recurrence, and they died shortly after discharge. One person declined device therapy and died while receiving comfort care. Lead malfunction was frequent. One patient experienced bradycardia arrest with failure of a TVP lead to capture, while another experienced lead dislodgement. Conclusion CHB secondary to ICI is often fatal. It should be considered in patients presenting with symptoms of myositis, raised troponin and increased QRS duration. Despite a small sample size, this study identifies several prognostic factors which can guide both patients and physicians with decision-making. Larger studies are needed to better understand the role of device therapy in this population.