Citations

Introduction: The physiological changes associated with aging have deleterious effects on cardiovascular function. In addition, increasing evidence showed the effect of exercise on improving cardiovascular health and reducing the aging process. The present study sought to demonstrate the association between exercise and biological age, estimated by our previously reported method using artificial intelligence-enabled electrocardiography (ECG). Methods: This retrospective observational study enrolled adults aged ≥18 years who have been evaluated at Mayo Clinic between 2019-2022 and completed the exercise questionnaire. The total time spent in moderate to strenuous exercise was calculated by multiplying the number of days engaging in exercise per week by the average minutes per day. The biological age was determined by applying our previously developed convolutional neural network model on the 12-lead ECG records (AI-ECG). The ECG records were within one year of subjects’ visits (in case of multiple visits, the closest one to the questionnaire was chosen). Positive Age-Gap (AI-ECG minus chronological age) reflects a person identified as being older by AI-ECG compared to his/her chronological age. Results: A total of 268,002 subjects (51% female) were recruited (mean age 59.7±16.4 years). Of those, 25.7% were not engaged in any exercise. The median day of engaging in exercise was 3 (Interquartile range, 2,5) per week, and the average time of exercising was 31.3±30 minutes/day. Age-Gap diminished progressively with increased duration of moderate to strenuous exercise (Figure 1). Linear regression analysis revealed exercise is an independent predictor of Age-Gap, (β= -0.043, 95%CI, -0.045 and -0.041, p<0.001). Conclusions: Engaging in moderate to strenuous exercise is associated with slower biological aging relative to chronological age as determined by AI-enabled ECG.

Introduction: Peripheral microvascular endothelial dysfunction (PMED) is a marker and precursor of atherosclerosis and is associated with an increased risk of cardiovascular events. The present study aims to identify the best cut-off value of PMED, assessed by the reactive hyperemia index, in predicting major adverse cardiovascular events (MACE). Additionally, we investigate whether integrating PMED to CHA2DS2-Vasc score improves the predicting accuracy of cardiovascular disease. Methods: this is a retrospective study of patients who underwent reactive hyperemia peripheral arterial tonometry (PAT). The optimal cut-off value of reactive hyperemia index associated with MACE was calculated using the area under the receiver-operating curve and the maximum Youden index. Traditional cardiovascular risk factors such as age, sex, congestive heart failure, hypertension, diabetes, stroke, vascular disease were determined to calculate the CHA2DS2-VASc score. MACE was defined as myocardial infarction, heart failure hospitalization, and cerebrovascular events. Results: 1,690 patients were enrolled (average age 51.1±13.9, 64.1% female). The optimal cut-off value of the reactive hyperemia index was 2.0 in the overall population and females and 2.17 in males. The risk of MACE during 10 (Interquartile range: 4,16) years of follow-up was 15.3%. Multivariable logistic regression revealed that PMED as an independent predictor of MACE (PMED: OR, 3.6, 95% CI, 2.6-4.9, p<0.001) (Table1). Furthermore, integrating PMED to CHA2DS2-VASc significantly improved the predictive accuracy (area under the curve, 0.747 vs. 0.708, p<0.001). Conclusion: PMED is a strong predictor of cardiovascular events. Non-invasive assessment of peripheral endothelial function may be useful in early detection and improving the stratification of high-risk patients for cardiovascular events.

Introduction: Newly developed Systematic Coronary Risk Evaluation-2 (SCORE-2) and the version for older people [(SCORE2-OP) ≥70 years] algorithms for 10-yr incident cardiovascular disease (CVD) have been derived incorporating European and US populations. Its performance has not been externally validated in community-based populations representative of real-world clinical practice. Hypothesis: We tested the hypothesis that the SCORE-2 and SCORE2-OP algorithms will accurately estimate 10-yr risk of first-onset CVD in this population. Methods: Consecutive patients who, between 1998-2000, sought primary care in Olmsted county, MN, and were followed-up using the Rochester Epidemiology Project. Inclusion criteria were set as those used in the derivation of the original algorithm. The composite outcome of CVD was defined as first myocardial infarction, ischemic stroke, or cardiovascular mortality. We compared predicted and observed events and generated C-statistics across predefined risk subgroups. Results: We included 22,858 adults, mean age of 55.11±11.58 (13.50% >70 yr) 54% females. After a mean follow-up of 9.55±1.5 yr, 2,145 events were observed. 6.39% of subjects for SCORE-2 and 59.88% using SCORE2-OP were considered at high risk. Overall, the SCORE-2 had better discrimination than the SCORE2-OP (C-statistic: 0.72 and 0.64, respectively) (Fig B-D). The algorithms performed better in individuals 50-69 yr while underpredicting in younger individuals and overpredicting CVD in ages above 70 (in the low and moderate risk group) (Fig A-C). Prediction was mostly similar between men, women and middle-aged individuals but demonstrated pronounced underprediction in older men (Fig B-D). Conclusions: The SCORE-2 Risk prediction tool performed with marginal results whereas the SCORE2-OP had poor performance when predicting CVD events in a community cohort representing real-world clinical practice in a non-European population.

Introduction: Mechanisms underlying bioprosthetic valve deterioration (BVD) are multifactorial and incompletely elucidated. Reparative circulating progenitor cells (CPCs), and conversely calcification-associated osteocalcin expressing CPCs (CPC-OCN), have been linked to native aortic valve deterioration. However, their role in BVD remains elusive. This study sought to evaluate the contribution of different subpopulations of CPCs in BVD. Methods: This prospective study enrolled 121 patients who had peripheral blood mononuclear cells (PBMC) isolated prior to bioprosthetic aortic valve replacement (surgical 104, transcatheter 17) and had an echocardiographic follow-up ≥2 years after the procedure. Using flow cytometry, fresh PBMC were analyzed for the surface markers CD34, CD133, and osteocalcin (OCN). BVD was evaluated by hemodynamic valve deterioration (HVD) using echocardiography, which was defined as an elevated mean transprosthetic gradient ≥30mmHg and/or at least moderate intraprosthetic regurgitation. Multivariable models were constructed to evaluate the association of each subpopulation of CPCs and other clinical characteristics with HVD. Results: Sixteen patients (13.2%) developed HVD during follow-up for a median of 5.9 years. Patients with HVD showed significantly lower levels of reparative CD34 + CD133 + cells and higher levels of OCN + cells than those without HVD (CD34 + CD133 + cells: 125 [80, 210] vs 270 [130, 420], P=0.002; OCN + cells: 3060 [523, 5528] vs 670 [180, 1930], P=0.005 respectively). Decreased level of CD34 + CD133 + cells was a significant predictor of HVD. Conclusions: Circulating levels of CD34 + CD133 + cells and OCN + cells were significantly associated with the subsequent occurrence of HVD in patients undergoing bioprosthetic aortic valve replacement. CPCs might play a vital role in the mechanism, risk stratification and a potential therapeutic target for patients with bioprosthetic valve deterioration.

Introduction: Recent studies have indicated high rates of future major adverse cardiovascular events in patients with Takotsubo cardiomyopathy (TTC). This study sought to evaluate the prognostic value of our institutional artificial intelligence-augmented electrocardiography (AI-ECG) algorithms in patients with TTC. Methods: This study enrolled consecutive patients in the prospective and observational Mayo Clinic Takotsubo syndrome registry. TTC was diagnosed according to the Mayo Clinic diagnostic. Our clinic’s previously developed and validated AI-ECG algorithms were used for detection of ECG-Age, probability of low ejection fraction, and probability of atrial fibrillation.Multivariable models were constructed to evaluate the association of AI-ECG and other clinical characteristics with major adverse cardiac events (MACE), defined as cardiac death, recurrence of TTC, nonfatal myocardial infarction, hospitalization for congestive heart failure, and stroke. Results: In the final analysis, 305 patients were studied over a median follow-up of 4.8 years. Patients with MACE were more likely to be older, have history of hypertension and chronic heart failure (CHF), worse renal function as well as having high-risk AI-ECG findings compared to those without. In the multivariate Cox proportional hazard analysis, the presence of 3 or 4 high-risk findings detected by AI-ECG, remained a significant predictor of MACE in the patients with TTC after adjusted by conventional risk factors (hazard ratio (HR) 2.17, 95% CI [1.33, 3.53], P=0.002; HR 2.44, 95% CI [1.38, 4.29], P=0.002, respectively). Conclusions: The combined use of developed AI-ECG algorithms derived from a single 12-lead ECG might identify ECG correlates of underlying non-transient myocardial dysfunction and detect subtle underlying patterns associated with worse outcomes in patients with TTC. This approach might be beneficial for stratifying high-risk patients with TTC.

Introduction: Physical activity is protective against cardiovascular (CV) disease and mortality, yet more than 25% of adults do not perform any regular exercise. Whole body electronic muscle stimulation (WB-EMS) is a novel FDA-approved device used for physical training that simultaneously stimulates all major muscle groups using percutaneous electrical impulse transmission during exercise. Preliminary studies demonstrated increased muscle mass, reduced fat mass, and improved functional capacity in elderly individuals who trained with WB-EMS. We evaluated the effects of training with WB-EMS on measures of CV health. Methods: Healthy adults were randomized to physical training with versus without WB-EMS for one 20-minute session each week for 16 weeks. Participants wore a specifically designed vest and arm and leg straps connected to the WB-EMS device (Miha Bodytec, Germany). Biphasic electrical stimulation was delivered through the vest and straps (4 sec on, 4 sec off) at a frequency that elicited a score of 5-6 on the Borg perceived exertion scale when each major muscle group was stimulated. Individuals randomized to no WB-EMS wore the same equipment but received no stimulation. Sessions were provided by trainers certified in WB-EMS training and consisted of a fixed protocol of simple exercises such as squats and lunges. Temporal changes in measures of CV health were compared between groups. Results: Forty-one individuals were recruited between 02/2021 and 02/2022 (n=24 WB-EMS, n=17 no WB-EMS; mean age 35.9±11.2 yrs; 61.3% females; median BMI 24.3 (21.8, 28.1) kg/m 2 . After 16 weeks there were significant and favorable differences in the intervention group compared to controls in waist: hip ratio (-1.2 cm vs. 0.9, p=0.05); total cholesterol (-1.1 mg/kg vs. 14.2 mg/kg, p=0.02); anaerobic threshold (68.2% vs. 30.8%, p=0.03); breathing efficiency (VE/VCO2: -10.36 vs -7.38, p=0.01); and peripheral endothelial function, measured with reactive hyperemia peripheral arterial tonometry (-0.009 vs. -0.29, p=0.06). Conclusions: Once weekly training with WB-EMS yielded more favorable changes in CV biomarkers compared to conventional training alone in healthy adults, and thus may offer an effective and time-efficient method of physical training.

A 41-year-old female with hyperlipidemia presented with typical exertional angina, dyspnea, and pre-syncope of 6 months duration. Physical examination was unremarkable. ECG showed low voltage QRS (Figure A), and Chest CTA was negative for obstructive-CAD, pulmonary emboli, aortic, and lung disease. Cardiac MRI was negative for myocarditis/pericarditis . Resting TTE was unremarkable with normal systolic and diastolic function. NT-Pro BNP, hs-CRP, serum/ urine protein electrophoresis, and free light chains ratio were normal. Regadenoson PET myocardial perfusion test showed a medium-sized area of stress-induced ischemia in mid/apical segments (Figure B) . Resting right heart Cath showed mean RA pressure (9mmHg) and RVEDP (10mmHg), mean PA pressure (19mmHg), and PCWP (15mmHg) with large v-waves, PCWP increased to 28mmHg with limited supine bike exercise, diagnostic of HFpEF (Figure C) . Angiography showed normal coronary arteries while coronary reactivity testing was diagnostic of severe epicardial and microvascular endothelial dysfunction (60% mid/distal LAD constriction and 19% decreased blood flow in response to intracoronary (IC) acetylcholine), and endothelial-independent microvascular dysfunction (coronary flow reserve 2.4 in response to IC adenosine), diagnostic of HFpEF due to coronary endothelial and microvascular disease (Figure D) . The patient’s symptoms improved at 2 weeks follow-up after initiation of furosemide, diltiazem, isosorbide mononitrate, and atorvastatin.

Abstract Background and Aims Arterial hypertension (HTN) in association with chronic kidney disease (CKD) is a global healthcare burden, yet clinically proven treatments are limited. electro-Hydraulic Acoustic Therapy (eHAT), using ∼10% of the energy used in shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. eHAT has been demonstrated to enhance healing in tissues such as bone, muscle, and myocardium, via several mechanisms, particularly by promoting neovascularization. Furthermore, previous animal studies demonstrated that eHAT reduces blood pressure (BP) and preserves renal function after ischemic kidney injury. The present pilot study explored the clinical safety and efficacy of eHAT and tested the hypothesis that eHAT would reduce BP and preserve renal function in patients with medically-treated hypertension and CKD. Method So far, a total of 15 patients with HTN and Stage III a/b CKD were enrolled in this prospective, single-arm study. The patients were treated with six sessions of eHAT during a 3-week period. At each session, 2400 shockwaves were applied to each kidney with 0.09 mJ/mm2 at 2.66Hz (NephrospecTM by Curespec LTD, Yehud, Israel). Follow-up (FU) visits were performed at 1, 3, and 6 months. Results The treatment was well tolerated with no major adverse events or need for analgesic treatment. Average Automated Office BP (AOBP) showed a strong tendency for a decrease in diastolic BP from baseline to the Primary Efficacy Objective at FU II (3 months post last treatment), which progressively decreased further at FU III (6 months) (Table 1). Similarly, average Office BP (OBP) detected a strong trend for a progressive decrease in systolic BP from baseline to the Primary Efficacy Objective (Table 1). Levels of eGFR appeared to slightly rise throughout the study, but this change has not reached statistical significance levels (Table 1). Conclusion The current study demonstrates that the eHAT procedure is tolerable and safe in this cohort. Moreover, a 3-week regimen tended to reduce BP and preserve eGFR in patients with controlled HTN and CKD. Therefore, electro-Hydraulic Acoustic Therapy may emerge as a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.

Injection of A-MSC-derived EVs harvested from patients who are lean can resolve myocardial injury in mice with experimental renovascular hypertension more effectively than A-MSC-derived EVs from patients with obesity. These observations underscore and might have important ramifications for the self-healing capacity of patients with obesity and for the use of autologous EVs as a regenerative tool.

Objective: Electro-Hydraulic Acoustic Therapy (eHAT), using ∼10% of the energy used in shockwave lithotripsy, is a promising technique to ameliorate ischemia and regenerate tissues. eHAT has been demonstrated to enhance healing in tissues such as bone, muscle, and myocardium, via several mechanisms, particularly by promoting neovascularization. Furthermore, previous animal studies demonstrated that eHAT reduces blood pressure (BP) and preserves renal function after ischemic kidney injury. The present pilot study explored the clinical safety and efficacy of eHAT and tested the hypothesis that eHAT would reduce BP and preserve renal function in patients with medically-treated hypertension and CKD. Design and method: So far, a total of 15 patients with HTN and Stage III a/b CKD were enrolled in this prospective, single-arm study. The patients were treated with six sessions of eHAT during a 3-week period. At each session, 2400 shockwaves were applied to each kidney with 0.09 mJ/mm2 at 2.66Hz (NephrospecTM by Curespec LTD, Yehud, Israel). Follow-up (FU) visits were performed at 1, 3, and 6 months. Results: The treatment was well tolerated with no major adverse events or need for analgesic treatment. Average Automated Office BP (AOBP) showed a strong tendency for a decrease in diastolic BP from baseline to the Primary Efficacy Objective at FU II (3 months post-last treatment), which progressively decreased further at FU III (6 months) (Table 1). Similarly, average Office BP (OBP) detected a strong trend for a progressive decrease in systolic BP from baseline to the Primary Efficacy Objective (Table 1). Levels of eGFR appeared to slightly rise throughout the study, but this change has not reached statistical significance levels (Table 1). Conclusions: The current study demonstrates that the eHAT procedure is tolerable and safe in this cohort. Moreover, a 3-week regimen tended to reduce BP and preserve eGFR in patients with controlled HTN and CKD. Therefore, electro-Hydraulic Acoustic Therapy may emerge as a novel, safe, and non-invasive alternative therapeutic approach in the management of HTN in the context of CKD.