Arsanjani, Reza

Current management of patients with congenital heart disease has increased their survival into adulthood. This is accompanied by potential cardiac complications, including pulmonary hypertension associated with congenital heart disease (PAH-CHD). PAH-CHD constitutes a challenging subgroup of pulmonary hypertension and requires expert management to improve quality of life and prognosis. Novel agents have shown a significant improvement in morbidity and mortality in patients with pulmonary arterial hypertension. However, the long-term effects of these medications on PAH-CHD patients remain somewhat uncertain, necessitating treatment plans largely founded on the clinical experience of the healthcare providers. The aim of this review is to summarize the current evidence and future perspectives regarding treatment strategies for PAH-CHD to help better guide management of this complex disease.

Introduction: Cardiac amyloidosis (CA) has been suggested to be common (up to 16%) in patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR). CA has poorer outcomes and its assessment in all TAVR patients may be costly and challenging. Hypothesis: CA may be screened for with an artificial intelligence (AI) clinical predictive model applied to pre-TAVR ECGs, and high probability (>50%) for CA may be associated with worse clinical outcomes. Methods: In this retrospective analysis of the Mayo institutional National Cardiovascular Disease Registry (NCDR)-TAVR, patients undergoing a TAVR between Jan-2012 and Dec-2017 were included. Pre-TAVR ECGs were analyzed by the AI predictive model for CA embedded in the EMR. EMRs were reviewed to assess for a clinical diagnosis of CA in those identified as high probability (>50%) by the AI tool. Clinical outcomes on 1 year follow-up were extracted from the NCDR-TAVR database and Kaplan-Meier curves were created to compare patients with high CA probability (≥50%) versus those with low probability (<50%). Results: Of 1070 patients who underwent TAVR (mean age 81.1± 8.5 years, 58.2% male), 263 (24.6%) had ≥50% probability for CA on pre-procedure ECG. Only 18 (1.7%) of these had clinical diagnosis of CA. In the survival analysis, high probability of CA by AI tool was associated with higher all-cause mortality (HR 1.60, 95%CI 1.09-2.34, p=0.01) and greater HF admissions (HR 1.59, 95%CI 1.08-2.35, p<0.01). Neither TIA/stroke nor myocardial infarction were statistically significant. MACE (TIA/stroke, myocardial infarction, heart failure admissions) was higher in the ≥50% CA probability group (HR 1.68, 95%CI 1.17-2.40, p<0.01), (Figure) . Conclusion: CA is clinically underdiagnosed in patients undergoing TAVR. AI applied to pre-TAVR ECGs suggesting higher probability for CA identifies a subgroup at higher risk of clinical events, who may benefit from further diagnostic evaluation for CA.

Introduction: Doppler mean gradient (MG) can underestimate the severity of aortic stenosis (AS) in patients with atrial fibrillation (AF) compared to patients in sinus rhythm (SR). Patients with AF and severe AS may experience delayed diagnosis and more advanced disease at time of referral for transcatheter aortic valve replacement (TAVR). Methods: Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. MG and aortic valve calcium score (AVCS) at time of referral were compared in patients in AF and SR. Retrospective theoretical AVCS in AF patients were derived assuming an average progression of 152 AU/year (published data). Results: There were 820 patients included; mean age was 81.3+/- 8.2 years and 41.6% were female. AF was present in 356 patients at time of referral. 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) and a lower peak velocity (4.1 vs. 4.2, p = 0.010) with a similar indexed aortic valve area (0.4 vs. 0.4, p = 0.17). Stratified by sex, the median calcium score for AF patients was higher (by around 300 AU) among both males (AF 2850.0 vs. SR 2561.0, p = 0.044) and females (AF 1942.0 vs. 1610.5, p = 0.025) ( figure 1 ). A density plot of retrospective theoretical AVCS in AF patients (projected assuming referral to TAVR approximately two years prior) resulted in nearly identical median AVCS between the two cohorts ( figure 2 ). Conclusions: Older age and higher AVCS in patients with AF compared to SR suggests that AS was both underestimated and more advanced at time of referral to TAVR. Patients in AF may have severe AS as early as 2 years prior to TAVR referral.

Background: Despite advancements in the management of cardiac amyloidosis, the contemporary estimates of the cardiovascular deaths (CVDs) in amyloidosis are not well-established. Objective: This study sought to assess the longitudinal trends of CVDs with comorbid amyloidosis and analyze the disparities in mortality in terms of race, gender, and geographical location. Methods: We queried the Centers for Disease Control and Prevention's Wide-Ranging Online Data for Epidemiologic Research database and performed serial cross-sectional analyses of national death certificate data for cardiovascular mortality with comorbid amyloidosis among patients aged 25 and above. Diseases of the circulatory system (ICD-10 I00-I99) were listed as the underlying cause of death, and amyloidosis (ICD-10 E85) as contributing cause of death. We calculated age-adjusted mortality rates (AAMRs) per 1,000,000 individuals and determined the trends over time by estimating the annual percent change using the Joinpoint Regression Program. Results: In the 22-year study period, 4,145 CVDs with comorbid amyloidosis in the United States were identified between 1999 and 2020. The AAMRs increased significantly from 0.69 per 1,000,000 individuals in 1999 to 2.13 per 1,000,000 individuals in 2020 (p< 0.05), with an annual percent increase of +3.92. The AAMRs for the span of 22 years were higher in males than females (1.66 vs. 0.75, p<0.05). When stratified by race, African American populations had the highest cumulative AAMR (2.34) compared to other racial groups. In terms of urbanization, the AAMR was significantly higher in the urban regions compared to the rural areas (1.15 vs. 0.91, p<0.05). Conclusion: The AAMRs from CVDs with comorbid amyloidosis have increased significantly over the past two decades, with significant disparities in male and African American individuals. This emphasises the need of further research in the development of effective treatments for amyloid heart disease.

Introduction: Exposure to high altitude results in hypobaric hypoxia, leading to physiological changes in the cardiovascular system that may result in dyspnea. Hypoxic simulation testing (HSTs) simulates changes in physiology that occur at a specific altitude. Hypothesis: The use of transthoracic echocardiography (TTE) during HST can detect the raise in right-sided pressures revealing underlying causes of high-altitude dyspnea. Methods: We performed a prospective observational study of consecutive patients with unexplained dyspnea at high altitude who were referred to an aerospace medicine program at a single institution between August 2021 and March 2023. Reduced FiO 2 was administered for 20 minutes to simulate altitude levels specific to patients’ history. TTE images were obtained at baseline and during peak hypoxia to evaluate right ventricular (RV) function, RV systolic pressure, and any possible shunts. Result: The study included 27 patients, with a mean age of 64.7 ±14.4 years and 14 (51.9%) females. No significant abnormalities were seen on baseline TTE and no significant differences in blood pressure and heart rate between baseline and hypoxia simulation were detected. Notably, RV systolic pressure increased at peak hypoxia, while RV systolic function declined as shown by a decrease in S’ wave and TAPSE ( Figure 1 ). Additionally, right to left shunts were present in 19 (70.4%) patients. Of these, four patients (21.1%) had shunts present at baseline with no changes at peak hypoxia, while the severity of shunts increased at peak hypoxia in eight cases (42.1%) and the shunts were only evident during hypoxia in seven patients (36.8%). Conclusion: TTE during HST provides valuable information by revealing the presence of symptomatic, sustained shunts and confirming the decline in RV hemodynamics explaining dyspnea at altitude. Further studies are necessary to establish the optimal clinical role of this physiologic method.

Introduction: The consequences of external cardiovascular compression and cardiac displacement from pectus excavatum (PEx) are debated. The complex geometry of the right (RV) and left ventricle (LV) along with distortion from the extrinsic chest deformity pose significant limitations to reliable assessment of LV and RV volumes and function using transthoracic 2D-echocardiography in this population. Hypothesis: A 3D-echocardiography approach can reliably assess the effects of external cardiac compression and the benefits of surgical correction on RV and LV function in PEx patients. Methods: Adult patients undergoing minimally invasive repair of PEx between Oct-2021 and Feb-2023 were included in this prospective study. Intraoperative transesophageal (TEE) 6 beat full volume video loops incorporating LV and RV were captured and compared before and after surgical correction of the PEx. TomTec Software® was used for offline 3D/4D reconstruction ( Figure 1 shows changes in 3D RV and LV shape pre- and post-surgery). Result: The study included 102 patients (mean age of 32.1 ±11.8 years; Haller index 4.9 ±2.5; 60.8% males). Post PEx repair, there was a significant (p<0.001) increase in the 3D RV volumes, RV ejection fraction (EF), RV stroke volume and RV strain ( Figure 1 ). Additionally, there was a significant improvement in 3D LVEF, 3D LV strain (longitudinal and circumferential), LV twist, and torsion ( Figure 1 ). Conclusion: In this PEx cohort, 3D/4D TEE imaging demonstrated significant increases in RV volumes and in RV and LV systolic function after surgical repair. These findings support the negative cardiovascular consequences of PEx compression and benefits of surgical repair.

Aortic valve stenosis (AS) is increasing in prevalence due to the aging population, and severe AS is associated with significant morbidity and mortality. Echocardiography remains the mainstay for the initial detection and diagnosis of AS, as well as for grading of severity. However, there are important subgroups of patients, for example, patients with low-flow low-gradient or paradoxical low-gradient AS, where quantification of severity of AS is challenging by echocardiography and underestimation of severity may delay appropriate management and impart a worse prognosis. Aortic valve calcium score by computed tomography has emerged as a useful clinical diagnostic test that is complimentary to echocardiography, particularly in cases where there may be conflicting data or clinical uncertainty about the degree of AS. In these situations, aortic valve calcium scoring may help re-stratify grading of severity and, therefore, further direct clinical management. This review presents the evolution of aortic valve calcium score by computed tomography, its diagnostic and prognostic value, as well as its utility in clinical care.

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

Chest radiography (CXR) is the most frequently performed radiological test worldwide because of its wide availability, non-invasive nature, and low cost. The ability of CXR to diagnose cardiovascular diseases, give insight into cardiac function, and predict cardiovascular events is often underutilized, not clearly understood, and affected by inter- and intra-observer variability. Therefore, more sophisticated tests are generally needed to assess cardiovascular diseases. Considering the sustained increase in the incidence of cardiovascular diseases, it is critical to find accessible, fast, and reproducible tests to help diagnose these frequent conditions. The expanded focus on the application of artificial intelligence (AI) with respect to diagnostic cardiovascular imaging has also been applied to CXR, with several publications suggesting that AI models can be trained to detect cardiovascular conditions by identifying features in the CXR. Multiple models have been developed to predict mortality, cardiovascular morphology and function, coronary artery disease, valvular heart diseases, aortic diseases, arrhythmias, pulmonary hypertension, and heart failure. The available evidence demonstrates that the use of AI-based tools applied to CXR for the diagnosis of cardiovascular conditions and prognostication has the potential to transform clinical care. AI-analyzed CXRs could be utilized in the future as a complimentary, easy-to-apply technology to improve diagnosis and risk stratification for cardiovascular diseases. Such advances will likely help better target more advanced investigations, which may reduce the burden of testing in some cases, as well as better identify higher-risk patients who would benefit from earlier, dedicated, and comprehensive cardiovascular evaluation.