Citations

Background: Refractory angina(Ang) effects 150 –250,000 pts in the US alone. These individuals have exhausted options for revasc and continue to have lifestyle limiting ang despite optimal medical Rx. Pre-clinical studies provided evidence that human CD34+ cells(CD34) can stimulate new blood vessel formation in ischemic myocardium(Myo), improving perfusion and function. We performed a phase 2 study of intraMyo injection of autologous CD34 in pts with CCS Class 3 and 4 Ang to obtain evidence for feasibility, safety and bioactivity. Methods: A phase 2 randomized, double-blind, placebo-controlled clinical trial was performed at 26 centers in the United States. There were 3 treatment groups: placebo, low dose (1×10^5 CD34/kg body wt) and high dose (5×10^5 CD34/kg). All pts underwent mobilization with GCSF 5 mcg/kg/day SC for 5 d, followed by apheresis on d5 to collect mononuclear cells. On day 6 CD34 were purified from the collected cells using the Isolex 300i device. After lot release testing, CD34 were injected endocardially at 10 locations in the ischemic Myo using the Myostar catheter following NOGA mapping. Placebo injections consisted of identical volumes of the diluent only. Results: A total of 167 pts were randomized and completed the injection procedure and 162 completed the 6 mo evaluation. The mean age of subjects was 61.0±8.9, there were 22 female and 145 male subjects. Trop was elevated in 26 pts at baseline and in 71 at some point following GCSF or injection. At 6 mo CD34 treated pts showed more reduction in ang frequency (−8.6 placebo vs 14.2 low dose) and improved ETT time (+69 sec placebo vs. +138 low dose). At 12m CD34 treated continue to show more reduction in angina (−8.2 placebo vs. −15.0 low dose) and improved ETT (+58 sec placebo vs. + 139 sec low dose). For key endpoints the high dose group results were inferior to low dose. The 12m data set has been locked and is being analyzed and the results of the completed analysis will be presented. Conclusions: Autologous CD34 cell therapy was associated with improved exercise tolerance and reduced angina in no-option pts with intractable angina. Ongoing analysis will determine endpoints, sample size and suitability of this therapy for a phase III study in no-option pts with refractory angina.

Background Percutaneous heart valve procedures have been increasingly performed over the past decade, yet real‐world mortality data on valvular heart disease (VHD) in the United States remain limited. Methods and Results We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database among patients ≥15 years old from 1999 to 2020. VHD and its subtypes were listed as the underlying cause of death. We calculated age‐adjusted mortality rate (AAMR) per 100 000 individuals and determined overall trends by estimating the average annual percent change using the Joinpoint regression program. Subgroup analyses were performed based on demographic and geographic factors. In the 22‐year study, there were 446 096 VHD deaths, accounting for 0.80% of all‐cause mortality (56 014 102 people) and 2.38% of the total cardiovascular mortality (18 759 451 people). Aortic stenosis recorded the highest mortality of VHD‐related death in both male (109 529, 61.74%) and female (166 930, 62.13%) populations. The AAMR of VHD has declined from 8.4 (95% CI, 8.2–8.5) to 6.6 (95% CI, 6.5–6.7) per 100 000 population. Similar decreasing AAMR trends were also seen for the VHD subtypes. Men recorded higher AAMR for aortic stenosis and aortic regurgitation, whereas women had higher AAMR for mitral stenosis and mitral regurgitation. Mitral regurgitation had the highest change in average annual percent change in AAMR. Conclusions The mortality rate of VHD among the US population has declined over the past 2 decades. This highlights the likely efficacy of increasing surveillance and advancement in the management of VHD, resulting in improved outcomes.

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

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.

Abstract Percutaneous Coronary Intervention (PCI) is a widely utilized standard ofcare and efficacious intervention in the management of coronary artery disease,improving prognosis and symptoms for many patients. Prediction of post-PCIoutcomes contributes to effective patient management and quality improvementinitiatives in healthcare. Our study focuses on comparative performance analysisfor state-of-the-art vision transformer (ViT) and convolutional neural network(CNN) on multimodal data analysis in a joint fusion framework. We integrateimages of electrocardiogram (ECG) data and tabular electronic health records(EHR) to predict 3 clinically relevant post-PCI (6 months) endpoints - heart failure hospitalization, all-cause mortality, and ischemic stroke. To design a comparativemodel for ViT, we proposed a new joint fusion architecture that consistsof a convolutional neural network (CNN) with a convolutional block attentionmodule (CBAM). The learned representations are combined at an intermediatelayer followed by processing these representations using a fully connectedlayer. The proposed model demonstrates excellent performance with the highestAUROC scores of 0.849, 0.913, and 0.794 for predicting heart failure hospitalization,all-cause mortality, and stroke, respectively. Surpassing the baseline EHRmodel and ViT, the proposed CNN+CBAM fusion model showcases superiorpredictive capabilities for heart failure prediction.

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.

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

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.