Lerman, Amir

Introduction: Blood pressure (BP) is a complex physiological marker. Cuffless devices, often based on photoplethysmography (PPG), enable frequent or continuous BP monitoring without arterial occlusion, enhancing comfort and usability in both inpatient and outpatient settings. Various devices have received regulatory clearance, but they are not yet included in clinical guidelines due to evolving validation standards. Aim: To evaluate accuracy of the Biobeat WP613 device for continuous BP monitoring using invasive intra-arterial pressure (IAP) monitoring in ICCU patients. Methods: This prospective, single-center study enrolled adults undergoing cardiac surgery at Chaim Sheba Medical Center (June 2020–January 2023) who had radial artery catheters for standard BP monitoring. Severe shock patients were excluded. Demographics and Fitzpatrick skin tone were recorded. ClinicalTrials.gov NCT04071015. Post-op, patients were simultaneously monitored with the standard IAP system and the Biobeat device. Continuous BP and HR were collected for up to five days. Data analyzed post hoc. Tested device The WP613 (Biobeat, Israel) is FDA-cleared, chest-worn, PPG-based device that uses multi-wavelength light and a sensor to monitor vital signs. It wirelessly transmits data to a cloud based algorithms to measure BP, cardiac output, stroke volume, and more. It also records a single-lead ECG and has a 5-day battery life. Results: A total of 96 patients were enrolled, with 88 included in the final BP analysis after excluding 8 due to technical issues. Of those, 80 received inotropic support. The average age was 63.2±12.2 years, with 33% female. Monitoring lasted an average of 25.6±17.2 hours, yielding over 78000 readings for each BP parameter and over 92000 HR readings (Fig 1) . Patients represented the full range of skin tones, classified using the Fitzpatrick scale I–VI. The Biobeat device showed excellent correlation with IAP monitoring: r=0.959 for SBP, 0.973 DBP, and 0.962 HR. Bland-Altman showed minimal bias (e.g., 0.1±4.8 for SBP) (Fig 2) . Correlation remained strong across BP ranges and skin tones. Heatmaps and representative cases confirmed close tracking between Biobeat and IAP (Fig 3) . Conclusion: The tested cuffless device (Biobeat) offers a high level of accuracy and agreement for BP and HR compared to data obtained by IAP monitoring in post-cardiac surgery patients. Further studies are needed to validate these findings in various populations and clinical settings.

Background: An increasing recognition of angina and nonobstructive coronary artery disease (ANOCA) underscores the importance of this patient group. While inflammation is a well-established key driver in the initiation and progression of atherosclerosis, its role in early stage is less clear. The current study was designed to assess the predictive value of monocyte-lymphocyte ratio(MLR) in comparison with hs-CRP in these patients. Method: This observational cohort study included patients with chest pain and nonobstructive coronary artery disease <40% stenosis in major coronary arteries on clinically indicated elective coronary angiography who underwent invasive physiological coronary reactivity testing for evaluation of coronary vasomotor function between 1997-2021. Preprocedural MLR was categorized as high (≥0.30) or low (<0.30) using the best cutoff value for predicting major adverse cardiovascular and cerebrovascular events (MACCE) determined by ROC curves. Preprocedural Hs-CRP levels ≥1 and <1 mg/L were classified as high or low, respectively. MACCE comprised cardiovascular death, nonfatal myocardial infarction, heart failure, stroke, and late revascularization. Kaplan-Meier plots, Log-rank test, and Cox regression analysis were used for analysis. Result: Among 892 patients (median age 52 [IQR: 43- 61] years, 69% females), 40% had high MLR and 49% had high hs-CRP, respectively. Over a 10-year follow-up, 125 patients (14%) experienced MACCE. In univariable analysis, high MLR level ( p < 0.001 ) and high hs-CRP ( p = 0.045) were associated with worse outcomes. (Figure 1) In multivariate Cox regression after adjusting for age, body mass index, creatinine, hypertension, hyperlipidemia, and diabetes mellitus, MLR remained a significant predictor of MACCE (HR=1.75, 95% CI=1.20- 2.55, p = 0.004), whereas hs-CRP lost its significance (HR=1.26, 95% CI=0.857- 1.848, p=0.241). Stratifying patients into four groups of high MLR/high hs-CRP (21%), high MLR/low hs-CRP (19%), low MLR/high hs-CRP (28%), and low MLR/low hs-CRP (32%) revealed that high MLR was associated with increased MACCE in both groups with high and low hs-CRP, while in both high MLR and low MLR groups, hs-CRP levels made no difference in MACCE incidences. (Figure 2). Conclusion: elevated MLR is a strong independent predictor of MACCE in patients with ANOCA, superior to hs-CRP. These findings highlight the potential of MLR as a valuable, readily available marker for risk stratification in early atherosclerosis.

Background: Sex differences in coronary physiology have been reported, particularly with regard to higher resting coronary flow in women. Resting flow is independently associated with clinical outcomes, irrespective of the presence of coronary microvascular dysfunction (CMD), but its sex-specific prognostic significance remains unclear. Aims: This study aimed to compare the prognostic implications of resting flow and CMD between sexes among patients with angina and non-obstructive coronary arteries (ANOCA). Methods: We studied 1194 patients with ANOCA undergoing coronary reactivity testing. Endothelium-independent microvascular function was assessed by coronary flow reserve (CFR) during adenosine-induced hyperemia, and endothelium-dependent function by coronary blood flow (CBF) increase during intracoronary acetylcholine infusion. Endothelium-dependent CMD was defined as <50% CBF increase, and endothelium-independent CMD as CFR <2.5. Cardiovascular events were defined as a composite of all-cause death, myocardial infarction and heart failure. Results: The median age of the study population was 52 years, and 71.1% were women. Resting average peak velocity (rAPV) and baseline CBF (bCBF) were significantly higher in women (p<0.001 and p=0.006, respectively). Survival analysis revealed that both elevated rAPV and bCBF were significantly associated with worse outcomes in men (p<0.001 and p=0.036, respectively, Figure 1), whereas no such associations were observed in women. In Cox proportional hazard analysis, sex showed a significant interaction effect with elevated rAPV (interaction p=0.014). Furthermore, endothelium-independent CMD was significantly associated with adverse outcomes in both men and women (p=0.011 and p=0.004, respectively), whereas endothelium-dependent CMD was significantly associated with prognosis only in men (p=0.006). Among men with endothelium-dependent CMD, the subtype characterized by higher bCBF was particularly associated with worse prognosis (p=0.001, Figure 2). Conclusions: In patients with ANOCA, men had lower resting coronary flow than women. However, its association with adverse outcomes was observed only in men, especially in those with impaired endothelial function. These results suggest that coronary physiology should be interpreted differently by sex, and that clinical decisions should be adjusted accordingly.

Purpose of review This paper reviews the current understanding of coronary vascular dysfunction (CVDys) in patients with angina and no obstructive coronary artery disease (ANOCA), based on recent findings from a comprehensive, large-scale study. It also discusses potential future directions for research and clinical practice. Recent findings CVDys involves enhanced vasoconstriction or impaired vasodilation caused by endothelium-dependent and/or -independent dysfunction in the epicardial or microvascular coronary arteries. It is classified into four subtypes based on anatomical location and underlying mechanisms, and can be assessed using coronary reactivity testing (CRT). Previous studies have evaluated their prognostic implications separately or in limited populations. A recent study assessed all subtypes within a single ANOCA cohort and confirmed that endothelium-dependent epicardial dysfunction and both types of microvascular dysfunction are associated with worse prognosis. Moreover, it demonstrated that microvascular function – both endothelium-dependent and -independent – serves as an independent prognostic factor for major adverse cardiovascular events. These findings emphasize the value of CRT-based comprehensive evaluation for risk stratification. Summary While evidence regarding the prognostic impact of CVDys has become increasingly robust, effective treatment strategies remain undefined. Future efforts should focus on developing CRT-guided interventions targeting coronary dysfunction, with the goal of improving clinical outcomes.

Abstract Importance Mesenchymal stromal cells (MSCs) possess therapeutic properties that mediate repair. Obesity impairs MSC functionality and therapeutic efficacy, possibly by eliciting dynamic modifications of epigenetic markers, like 5-hydroxymethylcytosine (5hmC). Objective We hypothesized that human obesity alters the 5hmC landscape and anti-inflammatory capacity of adipose tissue-derived MSCs to activate the prominent inflammatory signaling mediator Interleukin (IL)-1β. Design, Setting, Participants, Intervention Adipose tissue samples were collected from obese and lean individuals (body mass index ≥30 or &lt;30 kg/m2, respectively, n = 11 each) during weight-loss or kidney donation surgery. Main Outcomes and Measures MSCs were harvested and analyzed for 5hmC profiles (MeDIP-seq) and mRNA expression (RNA-seq) (n = 5 each). Subsequently, MSCs or a vehicle were injected into mice, (n = 6 each) and two-weeks later, kidneys were evaluated using in-vivo magnetic resonance imaging and ex vivo studies. The role of IL-1β was then studied in-vitro in MSC-induced immunomodulation using siRNA in macrophages. Results Compared to MSC from lean patients, obese-MSC genes showed 2087 differential 5hmC modifications and 175 differential mRNA expression. Among them, 14 genes with overlapping alterations were involved in regulation of cytokine production, prominently IL-1β. Injecting obese MSCs elevated renal expression of IL-1β and M1 macrophage count but lowered kidney perfusion. Silencing IL-1β in obese-MSCs in vitro reduced M1 phenotype switching in co-incubated macrophages. Conclusions and Relevance Obesity induces epigenetic and gene expression changes in MSCs, particularly in IL-1β, associated with impaired anti-inflammatory functionality of MSCs. Targeting IL-1β could be a useful therapeutic approach to modulate the decline in MSC functionality resulting from obesity.

Background: Previous studies have linked pericoronary artery adipose tissue attenuation to major adverse cardiac event (MACE). However, the association between pericarotid artery fat and prognosis remains underexplored. This study aimed to investigate the association between preoperative pericarotid fat characteristics and the subsequent prognosis in patients undergoing carotid endarterectomy (CEA). Methods: This study included patients with preoperative computed tomography angiography (CTA) followed by CEA. Preoperative neck CTA images were obtained and analyzed with novel methods using 3D Slicer software. We segmented the common and internal carotid arteries. The segment was horizontally trimmed, isolating the region around the bifurcation, extending 15 mm above and 10 mm below. Pericarotid fat was defined as adipose tissue within a 5 mm radial distance from the outer vessel wall, with Hounsfield units (HU) between -190 and -30 (Figure 1, carotid segmentation [green] and pericarotid fat [yellow]) . For each patient, we calculated the HU average and the volume (mm3) of the pericarotid fat. MACE was defined as a composite of all-cause mortality, myocardial infarction, and cerebrovascular events. The relationship between both pericarotid fat characteristics and MACE was investigated. Results: Of the 43 patients initially included, one was excluded due to an inability to perform segmentation caused by chronic total occlusion, leaving 42 patients (age 73 [67-78] years, 33 [76.7%] male). The comparison of mean pericarotid fat HU between the ipsilateral and contralateral sides showed no significant difference (-60.3±11.0 HU vs. -60.9 ±11.3 HU, p=0.437). However, the median ipsilateral fat volume was significantly higher than the contralateral volume (528 [248, 1100] mm3 vs. 328 [184, 697] mm3, p=0.020). When comparing patients with and without MACE, those with MACE had a significantly lower ipsilateral fat density (-59.4±10.2 HU vs. -66.8 ±11.1 HU, p=0.022) and a higher fat volume (468 [233, 746] mm3 vs. 845 [458, 1451] mm3, p=0.044). Kaplan-Meier analysis revealed that higher volume and lower fat density than the median were significant predictors of MACE (log-rank p=0.015 and p=0.042, respectively) (Figure 2). Conclusions: Assessment of pericarotid fat using a novel CTA analytic method in patients undergoing CEA identified ipsilateral lower fat density and higher fat volume as predictors of adverse outcomes.

Background: Atherosclerotic carotid artery disease is associated with a high risk of major adverse cardiac events (MACE) even with optimal risk factor management and surgical interventions such as carotid endarterectomy (CEA). Aortic stenosis (AS) is an age-related valve disease that is associated with a high rate of MACE. An artificial intelligence-based AS estimation algorithm (AI-AS) can identify AS with high accuracy using electrocardiogram. This study evaluates the prognostic value of AI-AS in patients with carotid artery disease undergoing CEA. Methods: We included patients with carotid artery disease undergoing CEA at Mayo Clinic from 2002-2023 if they had >30 days of follow-up and an electrocardiogram within one year before CEA. The electrocardiogram closest to the CEA date was used to calculate AI-AS (AS probability ranging from 0-1). MACE was defined as the composite of cardiac events, ischemic cerebrovascular accidents, and all-cause mortality during follow-up after CEA. A receiver operating characteristic curve and the Youden index were used to identify the optimal AI-AS cut-off value for predicting MACE. Kaplan Meier plot was used to depict MACE-free survival. Regression models were used to evaluate the predictive value of AI-AS for future MACE adjusting for clinical covariates. Results: A total of 665 patients with a median age of 72 [IQR:66, 78] years and 438 (65.9%) males were included. Over a median follow-up time of 7.1 [IQR:2.7, 11.5] years, MACE occurred in 419 (63%) of the patients, including 187 (44.6%) mortality, 161 (38.4%) cardiac events, and 71 (16.9%) cerebrovascular accidents. Median AI-AS was 0.32 [IQR:0.09, 0.55] in the total cohort, 0.34 [IQR:0.12, 0.56] in patients with MACE, and 0.30 [IQR:0.07, 0.53] in patients without MACE (P=0.038). AI-AS was a significant predictor of MACE (HR:2.38, 95%CI:1.64-3.46, P<0.001) in univariate Cox regression analysis. The optimal cut-off value of AI-AS for MACE was 0.419 (area under the curve: 0.55). Patients with high AI-AS (≥0.419) had a significantly lower MACE-free survival in the Log-rank test ( Figure 1 ) and in the multivariable Cox regression model adjusted for covariates compared to low AI-AS (<0.419) patients ( Table 1 ). Conclusion: AI-AS is an independent predictor of MACE in patients with carotid artery disease after CEA and can be used as a risk-stratifying tool in this patient population. Additional studies are needed to elucidate the mechanistic link between AS and MACE in these patients.

Background: The bovine aortic arch is a vascular variant in which the left common carotid artery originates from the brachiocephalic trunk rather than directly from the aortic arch. The bovine anatomical variation may alter the blood flow dynamics, potentially contributing to the formation and progression of carotid plaques. In this study, we evaluated the association of the bovine aortic arch and the severity of carotid stenosis. Methods: In this retrospective study, we included patients with carotid artery disease undergoing carotid endarterectomy (CEA) and pre-surgical computed tomography angiography (CTA). CTAs were reviewed to assess the carotid stenosis and the anatomy of the aortic arch. The left carotid artery was classified as normal if it originated from the aortic arch and as bovine if it originated from the brachiocephalic trunk (Figure 1) . Unlimited propensity score matching was performed to balance baseline characteristics between patients with bovine and normal anatomies. The Mann-Whitney U test was applied to compare carotid stenosis between bovine and normal arteries. Results: A total of 203 patients (bovine:23, normal:180) were initially enrolled. Using propensity score matching, 20 patients with bovine anatomy were matched to 45 patients with normal anatomy (Figure 2) . Among the 65 patients included, 47 (74.6%) were male, with a median age of 70 [IQR:65.0-76.0] years. Left-sided carotid artery disease was more prevalent in the bovine compared to normal group (N=12, 66.7% vs. N=16, 36.4%; p=0.030). Additionally, the severity of carotid stenosis in CEA-treated side was higher in patients with bovine arch compared to normal controls (82.5% [76.2-88.7] vs. 70.0% [50.0-95.0]; p=0.030) (Figure 3) . Conclusions: The association of a bovine aortic arch with more severe carotid stenosis suggests that this anatomical variant may be a marker for increased cerebrovascular risk.