Prior Revascularization Research Articles

Abstract P232: Toxic Stress is Associated With Greater Odds of Cardiovascular Disease Among Younger but Not Older Women in the Go Red for Research Dataset

Introduction: The incidence of certain cardiovascular diseases (CVD) such as heart attack and stroke have been increasing among younger women (ages 35-54 years). Psychosocial stress may be an important risk factor for CVD among this group of women. We examined whether toxic stress was associated with an increased odds CVD and whether this association was greater among younger women (< 55 years of age) compared to older women (≥ 55 years of age). Hypothesis: Toxic stress would only be associated with CVD among younger women. Methods: We utilized data from participants enrolled in the American Heart Association Research Goes Red Registry, an online research platform powered by Verily. Women were asked if they had been diagnosed with any of the following heart related conditions (heart attack, hemorrhagic stroke, prior revascularization, or blocked arteries). Women were also asked whether they had experienced toxic stress defined as a significant life-defining stressful activity over a prolonged period unaccompanied by sufficient social resources or support such as loss of a child, racial discrimination, or job loss. Logistic regression models were used to estimate odds ratios between toxic stress and CVD as well as differences by age (< 55 versus ≥ 55 years of age) using an interaction term. Results: The analytic dataset included 1,354 women who completed both the RGR Survey and the Healthcare and Experience Survey. The mean age of participants was 47.8 (SD: 12.6), 70% were less than 55 years of age, 83% were Non-Hispanic White, 59% indicated that they had experienced toxic stress, and 12% had CVD. In final multivariable models, there were significant differences in the association between toxic stress and CVD by age group (toxic stress-by-age interaction = 0.05) such that toxic stress was only significantly associated with an increased odds of CVD among women < 55 years of age (OR: 2.00; 95% CI: 1.17, 3.44; p-value: 0.0119). In contrast, toxic stress was not significantly associated with an increased odds of CVD among older women ≥ 55 years of age (OR: 0.97; 95% CI: 0.59, 1.61; p-value: 0.9052). Conclusions: Toxic stress was associated with an increased odds of cardiovascular disease among younger, but not older women in this cross-sectional study. Stress may be an underrecognized risk factor for CVD, especially among younger women who may benefit from interventions to mitigate and prevent stress. These findings should be corroborated in future longitudinal or other study designs that can establish temporality and stronger inferences of causality.

The Use and Impact of Cilostazol on Patients Undergoing Endovascular Peripheral Interventions

ObjectivesCilostazol is used for the treatment of intermittent claudication. The impact of cilostazol on the outcomes of peripheral vascular interventions (PVI) remains controversial. This study assesses the use and impact of cilostazol on patients undergoing PVI for peripheral arterial disease (PAD). MethodsThe Vascular Quality Initiative (VQI) database files for PVI were reviewed. Patients with PAD who underwent PVI for CLTI or claudication were included and divided based on the use of cilostazol preoperatively. After propensity matching for patient demographics and comorbidities, the short-term and long-term outcomes of the two groups (preoperative cilostazol use versus no pre-operative cilostazol use) were compared. The Kaplan-Meier method was used to determine outcomes. ResultsA total of 245,309 patients underwent PVI procedures and 6.6% (N=16,366) were on cilostazol prior to intervention. Patients that received cilostazol were more likely to be male (62% vs 60%; P < .001), White (77% vs 75%; P < .001), and smokers (83% vs 77%; P < .001). They were less likely to have diabetes mellitus (50% vs 56%; P < .001) and congestive heart failure (14% vs 23%; P < .001). Patient on cilostazol were more likely to be treated for claudication (63% vs 40%, P < .001), undergo prior lower extremity revascularization (55% vs 51%, P<.001) and less likely to have undergone prior minor and major amputation (10% vs 19%; P < .001) compared to patients who did not receive cilostazol. After 3:1 propensity matching, there were 50,265 patients included in the analysis with no differences in baseline characteristics. Patients on cilostazol were less likely to develop renal complications and more likely to be discharged home. Patients on cilostazol had significantly lower rates of long-term mortality (11.5% vs 13.4%, P <.001 and major amputation (4.0% vs 4.7%, P=0.022). However, there were no significant differences in rates of reintervention, major adverse limb events, or patency after PVI. Amputation-free survival rates were significantly higher for patients on cilostazol, after four years of follow-up (89% vs 87%, P=0.03). ConclusionCilostazol is underutilized in the VQI database and seems to be associated with improved amputation-free survival. Cilostazol therapy should be considered in all patients with PAD who can tolerate it prior to PVI.

A Practical Approach to the Management of Residual Cardiovascular Risk: United Arab Emirates Expert Consensus Panel on the Evidence for Icosapent Ethyl and Omega-3 Fatty Acids.

Patients with hyperlipidemia treated with statins remain at a residual cardiovascular (CV) risk. Omega-3 polyunsaturated fatty acids hold the potential to mitigate the residual CV risk in statin-treated patients, with persistently elevated triglyceride (TG) levels. We reviewed the current evidence on the use of icosapent ethyl (IPE), an omega-3 fatty acid yielding a pure form of eicosapentaenoic acid. REDUCE-IT reported a significant 25% reduction in CV events, including the need for coronary revascularization, the risk of fatal/nonfatal myocardial infarction, stroke, hospitalization for unstable angina, and CV death in patients on IPE, unseen with other omega-3 fatty acids treatments. IPE was effective in all patients regardless of baseline CV risk enhancers (TG levels, type-2 diabetes status, weight status, prior revascularization, or renal function). Adverse events (atrial fibrillation/flutter) related to IPE have occurred mostly in patients with prior atrial fibrillation. Yet, the net clinical benefit largely exceeded potential risks. The combination with other omega-3 polyunsaturated fatty acids, in particular DHA, eliminated the effect of EPA alone, as reported in the STRENGTH and OMEMI trials. Adding IPE to statin treatment seems to be cost-effective, especially in the context of secondary prevention of CVD, decreasing CV event frequency and subsequently the use of healthcare resources. Importantly, IPE has been endorsed by 20 international medical societies as a statin add-on treatment in patients with dyslipidemia and high CV risk. Robust medical evidence supports IPE as a pillar in the management of dyslipidemia.

Surgery and transcatheter intervention for degenerative mitral regurgitation in the United States

ObjectivesWe evaluated practice trends and 3-year outcomes of transcatheter edge-to-edge repair (TEER) and surgical repair for degenerative mitral regurgitation in the United States. MethodsFrom the Centers for Medicare and Medicaid Services data (2012-2019), 53,117 mitral valve interventions (surgery or TEER) were performed for degenerative mitral regurgitation, identified by excluding rheumatic and congenital disease, endocarditis, myocardial infarction, cardiomyopathy, and concomitant or prior coronary revascularizations. Median follow-up was 2.9 years (interquartile range, 1.2-5.1 years). End points were 3-year survival, stroke, mitral reinterventions, and heart failure readmissions. ResultsVolume of total annual mitral interventions did not significantly change (P = .18) between 2012 and 2019. However, surgical cases decreased by one-third, whereas TEER increased. Among 27,170 patients (52.5% men; mean age, 73.5 years) who underwent TEER (n = 7755) or surgical repair (n = 19,415), surgical patients were younger (71.8 vs 80.8 years; P < .001), with less comorbidity and frailty. In 4532 patient pairs matched for age, frailty, and comorbidity, 3-year survival after TEER was 65.9% (95% CI, 64.3%-67.6%) and 85.7% (95% CI, 84.5%-86.9%) after surgery (P < .001). Three years after TEER or surgery, stroke rates were 1.8% (95% CI, 1.5%-2.2%) and 2.0% (95% CI, 1.6%-2.4%) (P = .49); heart failure readmission rates were 17.8% (95% CI, 16.7%-18.9%) and 11.2% (95% CI, 10.3%-12.2%) (P < .001); and mitral reintervention rates were 6.1% (95% CI, 5.5%-6.9%) and 1.3% (95% CI, 1.0%-1.7%) (P < .001), respectively. ConclusionsAmong Medicare beneficiaries with degenerative mitral regurgitation, an increase in TEER utilization was associated with worse survival, increased heart failure readmissions, and more mitral reinterventions. Randomized trials are needed to better inform treatment choice.

FEATURES OF THE COURSE OF MYOCARDIAL INFARCTION IN PATIENTS WITH NOVEL CORONAVIRUS INFECTION

HighlightsAccording to a single-center comparative registry study, patients with myocardial infarction and new coronavirus infection can be characterized by a higher frequency and severity of hyperglycemia, as well as acute heart failure (alveolar pulmonary edema) upon admission to the hospital against with severe comorbidity (due to type 2 diabetes mellitus and a previous stroke). Type 2 diabetes mellitus can be considered a disease that makes a significant contribution to a more unfavorable course of myocardial infarction against the background of a new coronavirus infection, as well as presumably to the structure of long-term adverse outcomes in this group of patients. AbstractAim. To comparatively analyze the period of inpatient care in patients with myocardial infarction (MI) complicated by the novel coronavirus infection (COVID-19).Methods. The retrospective single-center register study involved 591 patients with MI. Of them 399 (67.5%) were men, and 192 (32.5%) were women, the mean age was 64.5 (58.0; 72.0) years. Taking into account the verified COVID-19, two groups of patients were formed. The first group included 478 (80.9%) patients with isolated MI, the second group included 113 (19.1%) patients with MI and COVID-19. A comparative assessment of demographic, clinical and anamnestic characteristics, the results of laboratory and instrumental tests and the frequency of adverse events during hospitalization in both groups was carried out. Moreover, the data of patients with a fatal outcome were analyzed as well.Results. Patients with MI and COVID-19 were characterized by a higher frequency of prior revascularizations (23.9 vs. 12.7, p = 0.025), including coronary artery bypass grafting (7.1 vs. 2.9%, p = 0.049), stenting (16.8 vs. 9.8%, p = 0.034), and bleeding (9.8 vs. 2.7%, p = 0.002). Patients with MI and COVID-19 presented with a higher level of hyperglycemia (7.7 (6.0; 11.4) versus 6.0 (5.2; 8.0) mmol/L, p&lt;0.001) and a comparable prevalence of type 2 diabetes mellitus. During the period of index hospitalization, patients with COVID-19 developed pulmonary edema 1.8 times more often, despite the fact that the incidence of acute heart failure ≥ class II according to Killip was 1.7 times higher in the group with isolated MI. Among all patients with MI, fatal outcome was registered in 89 (18.6%) cases, with the comparable frequency in the groups – 14.6 and 18.6%, respectively. At the same time, patients with MI and COVID-19 who died during hospitalization were characterized by a higher frequency of type 2 diabetes mellitus (3.6 times) and a prior stroke (3.7 times). The most common cause of fatal outcomes was pulmonary edema, which developed 2.3 times more often in patients with MI and COVID-19 than in patients with isolated MI.Conclusion. There were no significant clinical differences between patients with MI and COVID-19 and patients with isolated MI, except for higher glycemia levels. A similar pattern has been discovered for in-hospital mortality. At the same time, the frequency of type 2 diabetes mellitus, prior stroke and pulmonary edema was higher in deceased patients with COVID-19.

Angiogenic gene therapy for refractory angina: results of the epicardial delivery of XC001 gene therapy for refractory angina coronary treatment (EXACT) phase 2 trial

Abstract Background Refractory or "no option" angina (RA) is a debilitating condition with increasing global prevalence. Exogenous transduction of vascular endothelial growth factor (VEGF) induces angiogenesis and improves perfusion of ischemic myocardium in preclinical studies. XC001 (AdVEGFXC1) is a novel adenoviral-5 vector expressing the three major isoforms of VEGF (-121, -165, -189) in ratios shown to enhance potency and improve safety. Purpose EXACT is a single-arm, multicenter, open-label, phase 2 trial to explore the safety, tolerability, and preliminary efficacy of trans-epicardial delivery of XC001 to improve exercise capacity and ischemic burden in RA patients. Methods Patients were required to have stable Canadian Cardiovascular Society (CCS) class II-IV angina on maximally tolerated medical therapy with exercise limited by angina after 90 but before 540 seconds on a modified Bruce protocol, demonstrable ischemia on stress positron emission tomography (PET) and lack revascularization options. XC001 (1x1011 viral particles) was injected directly into ischemic myocardium via surgical transthoracic epicardial access. The primary outcome was safety by adverse event monitoring. Efficacy assessments included difference from baseline to six months in total exercise time (TET), myocardial ischemia by PET, angina class, angina frequency, and quality of life. Results Thirty-two patients (mean/median ages of 64/64, 34% female) were enrolled at 13 sites between March 2021 and July 2022. Median anti-anginal use was 3, 75% had prior revascularization with CABG and 88% with PCI. Fifty-five serious adverse events (SAEs) were observed in 21 patients (66%). None were attributed to study drug. Twenty-one SAEs in 14 patients were related to the surgical procedure, all of which were expected. One non-CV death occurred in month 3 following respiratory infection (Covid) deemed unrelated to surgery or study drug. Compared to baseline, total exercise time at 6-months increased by 85.5 seconds (95% CI 31.3-139.7) [Figure 1A] while total myocardial ischemic deficit in the treated region on PET decreased by 14.4% (95% CI, 3.01–25.73) [Figure 1B]. Angina frequency and nitroglycerin use measured during a two-week diary decreased by 6.6 episodes (95% CI, 3.5–9.7) and 4.1 doses (95% CI, 1.3–6.9), respectively. Canadian Cardiovascular Society angina grade decreased from 3.1 to 1.8, mean difference 1.3 classes (95% CI, 1.0–1.6) [Figure 2] while Seattle Angina Questionnaire Frequency score improved from 41.3 to 67.4, mean difference of 26.1 (95% CI, 16.3–35.9). Conclusions VEGF gene therapy with XC001 administered via minimally invasive epicardial delivery appears safe and well tolerated. Improvements in objective and subjective measures including total exercise time, myocardial perfusion, angina frequency and quality of life support a clinically meaningful biologic effect. This therapy warrants study in larger randomized studies.

Life expectancy in women and men after STEMI: a comparison to a matched general population

Abstract Background/Introduction ST-elevation myocardial infarction (STEMI) is considered a risk factor for short- and long-term mortality. Further, studies indicate that female sex is associated with increased mortality among STEMI patients. Our aim was to assess the impact of female and male sex on short- and long-term excess mortality in comparison to matched general populations. Methods We identified all patients undergoing first-time percutaneous coronary intervention (PCI) who were treated with primary PCI (pPCI) for STEMI from 2003 to 2018 in the Western Denmark Heart Registry (covering approximately 3.3 million inhabitants). Each patient was matched in a 1:5 ratio by age and sex with individuals from the Western Denmark general population without prior myocardial infarction or coronary revascularization. To assess excess mortality after STEMI, we compared mortality in women and men to their matched general population using a stratified Cox proportional hazards model. Excess mortality was assessed in the periods from 0-30 days, 31-90 days, and 91 days – 4 years of follow-up. Results A total of 18,216 pPCI-treated STEMI patients were included, 4,833 (26.5%) women and 13,382 (73.5%) men. The matched general population cohort consisted of 91,075 individuals, 24,165 women and 66,910 men. Median age at STEMI diagnosis was 68 years (IQR 58-78) in women and 62 years (54-71) in men. Excess mortality was markedly higher in the first 30 days after STEMI with the relative risk being 35 times higher for both women (hazard ratio (HR) 34.63, 95% CI 26.11-45.95) and men (HR 35.18, 28.48-43.48) compared to their matched general populations. From 31-90 days, the excess mortality remained higher after STEMI for women (HR 3.58, 2.58-4.97) and men (HR 2.00, 1.58-2.55). However, in the 91 days - 4 years follow-up period there was only a marginal unadjusted 13% excess mortality in women (HR 1.13, 1.02-1.25) while an 8% lower mortality was observed in men (HR 0.92, 0.86-0.98; p for interaction&amp;lt;0.05). After adjusting for comorbidities in the 91 days - 4 years period, an excess mortality in women was no longer observed (HR 1.03, 0.93-1.14), while men with STEMI remained at lower risk than the general population (HR 0.87, 0.81-0.94). Conclusions In a large, contemporary STEMI cohort mortality within the first 30 days were 35 times higher in both women and men when compared to mortality in an age- and sex- matched general population. However, STEMI patients surviving the first 90 days were no longer at higher risk than their matched general population individuals; the latter most likely reflecting guideline-directed prophylactic interventions.Excess mortality in women with STEMIExcess mortality in men with STEMI

High-sensitivity troponin-i and risk of heart failure in individuals with suspected acute coronary syndrome

Abstract Background Serial high-sensitivity cardiac troponin-I (hsTnI) concentrations are associated with short- and long-term mortality and recurrent ischemic events in individuals with suspected acute coronary syndrome. However, the relation to subsequent heart failure events is less well established. Purpose To examine the association between single and serial hsTnI concentrations and subsequent hospitalization or outpatient contact for heart failure in subjects with suspected acute coronary syndrome. Methods Using Danish national registries, we identified persons without known heart failure who underwent two hsTnI measurements (Siemens TnI Flex® Reagent, 99th percentile upper reference limit, 45 ng/l) separated by 1-7 hours, during hospitalization for myocardial infarction, unstable angina, observation for suspected myocardial infarction, or chest pain from 2012 through 2019. Individuals were stratified according to their hsTnI concentration pattern from first to second measurement (main groups: normal, rising, persistently elevated, or falling) and the magnitude of hsTnI concentration change (secondary groups: &amp;lt;20%, &amp;gt;20 to 50%, or &amp;gt;50% in either direction). Finally, they were grouped into quantiles based on the first hsTnI measurement (&amp;lt; = 15 ng/l, 16-30 ng/l, 31-44 ng/l, &amp;gt; = 45 ng/l) to explore whether the risk of heart failure was greater with higher hsTnI concentrations. We calculated standardized risks of hospitalization or outpatient contact for heart failure using multivariable logistic regression with average treatment effect modeling. Results A total of 18,939 individuals were included of whom 21.9% were discharged with a diagnosis of myocardial infarction, 4.8% with unstable angina, and 73.3% with observation for suspected myocardial infarction or chest pain. Median age was 61.9 years, and 52.5% were male. With respect to known cardiovascular disease, 17.6% had coronary artery disease, 5.4% had undergone prior coronary revascularization, and 8.0% had atrial fibrillation or flutter. A total of 429 individuals received a diagnosis of heart failure within the first 30 days while an additional 526 were diagnosed from days 31-365. The standardized absolute risk was lowest in subjects with two normal hsTnI values (days 0-30: 0.45%; days 31-365: &amp;lt;0.01%) and highest in those with persistently elevated concentrations (days 0-30: 8.56%; days 31-365: 9.50%) (Figure). The degree of hsTnI within each main group did not appear to affect the risk of heart failure. Conversely, the risk of heart failure was positively associated with hsTnI concentrations measured on the first sample. Conclusions Among individuals with suspected acute coronary syndrome, those with a persistently elevated hsTnI concentration consistently had the highest risk of a subsequent hospitalization or outpatient contact for heart failure. In addition, there appeared to be a dose-response relationship between hsTnI concentrations and the risk of heart failure.Figure

Abstract 14894: The Impact of Coronary Artery Disease on Cardiovascular Events Differs Between Men and Women in the PARTNER Trials

Introduction: Among individuals with severe aortic stenosis (AS), there is significant heterogeneity in the burden of coronary artery disease (CAD). Hypothesis: We hypothesize that a greater CAD burden will be associated with increased adverse events after AS treatment. Methods: Patients with severe AS in the PARTNER (Placement of Aortic Transcatheter Valves) 1, 2 and 3 trials and registries were categorized by CAD burden. Clinical characteristics, imaging, treatment, and outcomes were compared between those with obstructive CAD [defined invasively as coronary stenosis ≥50%, prior myocardial infarction (MI) or revascularization] and patients with no or non-obstructive CAD (all stenoses &lt;50% and no prior MI or revascularization). The primary endpoint was cardiovascular (CV) death or heart failure (HF) hospitalization at 2 years. Results: Among 8058 patients with severe AS, 2200 (27.3%) had non-obstructive or no CAD and were more likely to be female (61.2%) with fewer CAD risk factors. Left ventricular (LV) mass index and LV dimensions were smaller and LV ejection fraction was higher among those with non-obstructive or no CAD. TAVR was performed in 72.0% of non-obstructive or no CAD patients and in 81.3% of patients with obstructive CAD (p&lt;0.0001); the remaining patients received SAVR. After adjustment for clinical, imaging, and AS treatment differences, the rate of CV death or HF hospitalization was higher among those with obstructive CAD (HR 1.16, 95% CI: 1.03-1.30, p=0.01). However, there was a significant sex-related difference in the primary outcome particularly between males and females with non-obstructive or no CAD, p interaction =0.003 (Figure). Conclusions: Patients with a greater burden of CAD had worse clinical outcomes after treatment for severe AS. However, there was a significant interaction by sex. Further study is needed to understand the increased CV risk among females compared to males with non-obstructive or no CAD.

Abstract 17625: Comparative Analysis of Mortality and Amputation Rates in Patients Undergoing Atherectomy for Infra-Popliteal Peripheral Arterial Disease: Insight From the VQI

Introduction: Infra-popliteal peripheral arterial disease (IPPAD) poses challenges due to complex vasculature. The BASIL-2 trial demonstrated superiority in endovascular treatment compared with surgical bypass in patients with IPPAD. However, the choice of endovascular modality has not been conclusive. Hypothesis: Combining plain balloon angioplasty (POBA)+atherectomy is associated with improved clinical outcomes compared to POBA. Methods: Patients that underwent POBA vs POBA+Atherectomy for IPPAD from the Vascular Quality Initiative database were identified. Propensity score matching (PSM) was employed to balance the distribution of confounding variables for mortality identified on multivariable logistic regression. Patient characteristics and long-term outcomes between the two treatment groups were compared. Results: A total of 10,494 individuals (74.6%) were treated with POBA, while 3,569 (25.4%) were treated with POBA+atherectomy. PSM ensured minimal differences in baseline characteristics, such as indication for procedure and prior revascularization. The atherectomy group was associated with higher technical success and lower perioperative complications, such as renal complications and hematoma, at the expense of higher rates of distal embolization. During long term follow up, patients who underwent atherectomy had lower rates of major amputation but lower freedom from reintervention. There were no differences in major adverse limb events and mortality. Conclusion: Combining POBA with atherectomy appears to be a safe approach in IPPAD, with lower rates of long-term amputation at the cost of higher risk for future re-intervention.

Abstract 14577: Electrocardiogram Parameters for Predicting the Severity of Coronary Artery Disease in Non-ST Segment Elevation Acute Coronary Syndrome

Background: Quantitative electrocardiogram (ECG) parameters have been found to correlate with severity of coronary artery disease (CAD). Thus, it may serve the purpose of risk stratifying patients with non-ST segment elevation acute coronary syndrome (NSTEACS). But little is known about the accuracy of each parameter.So, this study was done to assess the correlation of ECG parameters with severity of CAD in patients with NSTEACS and to compare the diagnostic accuracy among them. Methods: 178 patients with NSTEACS with left ventricular ejection fraction &gt;50% were selected for the study after excluding patients with heart failure, arrhythmia, prior myocardial infarction or revascularisation. P wave peak time (PWPT), corrected QT dispersion (cQTd) and QT dispersion ratio (QTDR) was calculated in all patients. CAD severity was assessed visually by coronary angiography and calculating the syntax score. Results: PWPT, cQTd and QTDR were increased significantly in patients with left main (LM) or triple vessel disease (TVD) than others. These parameters also showed a strong positive correlation with the syntax score ( P&lt;.001 ). Among these parameters, cQTd showed the best diagnostic accuracy (76% sensitivity and 64% specificity) to detect LM or TVD with a cut-ff value of 74 ms. Conclusion: PWPT, cQTd and QTDR may help to identify high risk patients with NSTEACS and early invasive procedure can be done to salvage a large area of myocardium at jeopardy. These may be particularly helpful to the physicians in periphery who have limited resources. Keywords: coronary artery disease, non-ST segment elevation acute coronary syndrome, P wave peak time, corrected QT dispersion, QT dispersion ratio

Abstract 16126: Sex Differences in the Relationship Between Left Ventricular Global Longitudinal Strain and Abnormal Myocardial Flow Reserve in a Patient Population With Sleep Disordered Breathing

Introduction: Obstructive sleep apnea (OSA), a form of sleep disordered breathing (SDB), is associated with abnormal myocardial flow reserve (MFR), a precursor to heart failure with preserved ejection fraction (HFPEF). Sex differences have been reported in the prevalence of abnormal MFR and OSA. However, it is unknown if there are sex differences in the relationship between left ventricular (LV) global longitudinal strain (GLS) and abnormal MFR in a patient population with SDB. Methods: We compared LV GLS among patients in our institution who had sleep testing for obstructive sleep apnea (OSA), cardiac PET stress test and an echocardiogram between 2015 and 2019. We reprocessed the echocardiograms using a vendor neutral software to obtain the two-dimensional LV GLS. Results: Among the 148 participants, 59% were female. Compared with females, males had lower BMIs, a higher prevalence of prior myocardial infarction or revascularization, and a greater severity of nocturnal airway obstruction and hypoxia. Males also had a greater proportion with abnormal LV GLS (≥ -17). See Table. The prevalence of abnormal MFR (&lt; 2.0) was higher among participants with abnormal LV GLS ( P = 0.031). This association was persistent among males but was lost among females (see Figure ). In age and sex adjusted logistic regression persons with abnormal LV GLS had 2X the odds of abnormal MFR (OR 2.3; 95% CI: 1.02 - 5.03). Among males, this association was significant (OR 4.8; 95%CI:1.5 - 13.7). No association observed among females. Formal interaction analyses did not meet statistical significance ( P int = 0.106). Conclusions: In this patient population with SDB, there was a significant association between LV GLS and abnormal MFR. The sex differences in the relationship may be due to differences in the severity of OSA and prevalence of ischemic heart disease. Future studies should clarify these relationships and elucidate the drivers of the sex disparities observed in these findings.

Abstract 14745: Stem Cell Factor Associated With Critical Limb Ischemia in Patients With Peripheral Artery Disease

Introduction: Critical limb ischemia (CLI) and related amputation (AMP) are severe manifestations of peripheral artery disease (PAD). The pathobiology of CLI/AMP is multifactorial including chronic ischemia in the context of large vessel and microvascular disease. Novel biomarkers may identify potential pathways for new therapies to prevent and treat CLI. Hypothesis: Exploration of the proteome will yield insights into new proteins and hence pathways relevant in the pathogenesis and complications of PAD. Methods: A nested case-control study including 50 patients with CLI/AMP and 83 without was assembled from patients with PAD in the TRA2P-TIMI 50 trial for proteomic exploration using the Olink CVDII panel. Candidate markers were identified based on a false discovery rate (FDR) p-value &lt;0.05 and then validated among 7,077 patients with PAD from TRA2P-TIMI 50 and FOURIER trials. Biomarkers were evaluated continuously &amp; by quartile and analyses adjusted for age, sex, diabetes mellitus, and prior peripheral revascularization. Results/Data: A total of 12 protein biomarkers were significantly associated with CLI/AMP in the case-control sample at an FDR of 5% (Fig-Panel A). Three remained significantly associated with CLI/AMP in the validation step, the strongest of which was stem cell factor (SCF), a cytokine expressed by endothelial cells and involved in vasculogenesis. There was a significant inverse association between SCF and CLI/AMP (p-Bonferroni 0.00047). Examined by quartiles and adjusting for baseline differences (Panel B), a graded inverse association between SCF and CLI/AMP was observed (Q4 vs Q1 Adjusted OR 0.52, 95% CI: 0.34, 0.77; p=0.002). Conclusions: A proteomic approach to identifying novel biomarkers associated with CLI/AMP revealed a strong inverse risk relationship with SCF levels. These data suggest that SCF and its effects on vasculogenesis warrant further investigation as a pathway to prevent and treat CLI/AMP in patients with PAD.

Clinical and procedural outcomes of percutaneous coronary intervention for de novo lesions involving the ostial left circumflex coronary artery.

Percutaneous treatment for ostial left circumflex artery (LCx) lesions is known to be associated with suboptimal results. The present study aims to assess the procedural and long-term clinical outcomes of percutaneous coronary intervention (PCI) for de novo ostial LCx lesions overall and according to the coronary revascularization strategy. Consecutive patients undergoing PCI with second generation drug eluting stents or drug coated balloons for de novo ostial LCx lesions in three high-volume Italian centers between 2012 and 2021 were retrospectively evaluated. The primary endpoint was target-vessel revascularization (TVR) at 2 years. Secondary endpoints included major adverse cardiovascular and cerebrovascular events (MACCE), target lesion revascularization, myocardial infarction, stroke, all-cause death, and repeat revascularization. A total of 366 patients were included in the analysis with a median follow-up of 901 (IQR: 450-1728) days. 79.5% of the patients were male, 33.6% were diabetic, 49.7% had a previous PCI, and 23.1% a prior surgical revascularization. Very ostial LCx stenting was performed in 34.1%, crossover from left main to LCx in 17.3%, and a two-stent strategy in 48.6% of cases, respectively. In the overall population, the incidence of TVR at 2 years was 19.0% while MACCE rate was 25.7%. No major differences in clinical outcomes were found according to the stenting strategy. Use of intracoronary imaging was associated with fewer MACCE (HR: 0.47, 95% CI: 0.25-1.13, p = 0.01), while the diameter of the stent implanted in the ostial LCx was associated with less TVR (HR: 0.43, 95% CI: 0.25-0.75, p = 0.002). Percutaneous revascularization of the ostial LCx is associated with a high rate of TVR, regardless of the stenting strategy. Intracoronary imaging and proper stent sizing may reduce the failure rates.

Intravascular lithotripsy compared to rotational atherectomy for the treatment of calcified distal left main coronary artery disease: A single center experience.

The safety and efficacy of intravascular lithotripsy (IVL) for the treatment of calcified distal left main (LM) disease remains unclear, especially compared to rotational atherectomy (RA). We retrospectively analyzed the baseline clinical, angiographic, intravascular ultrasound (IVUS) characteristics and procedural outcomes of 107 patients who underwent distal LM percutaneous coronary intervention (PCI) with IVL (with or without adjunct atherectomy) versus RA alone for plaque modification before stenting at a single center between 2020 and 2022. A total of 50 patients underwent calcium modification with IVL with or without adjunct atherectomy and 57 with RA only. The mean age was 73 years and with a high prevalence of diabetes (58.9%), chronic kidney disease (42.1%), prior revascularization (coronary artery bypass graft surgery [36.4%] or prior PCI [32.7%]). Acute coronary syndrome was the primary indication for PCI in over 50% of the patients in both groups. Medina 1-1-1 LM bifurcation disease was identified in 64% and 60% of the IVL and RA groups (p = 0.64) respectively. Final minimum stent area in distal LM (>8.2 mm2 ), ostial LAD (>6.3 mm2 ) and ostial LCX (>5.0 mm2 ) were achieved in 96%, 85% and 89% of cases treated with IVL respectively and 93%, 93% and 100% of cases treated with RA respectively (LM p = 1.00; LAD p = 0.62; LCX; p = 1.00 for difference between the two groups). Procedural success (technical success without in-hospital major adverse events) was achieved in 98% of the IVL group and 86% of the RA-only group (p = 0.04). There were eight procedural complications (flow-limiting dissection, perforation, or slow/no-reflow) in the RA group compared to four in the IVL group (NS), and one patient in the RA required salvaged mechanical support compared to none in the IVL group. Plaque modification with coronary IVL appears to be efficacious and safe for the treatment of severely calcified distal LM lesions compared to RA only. Larger randomized studies are needed to confirm these findings.

Choroid plexus vascular reactivity in moyamoya: Implications for choroid plexus regulation in ischemic stress.

Choroid plexus (ChP) hyperemia has been observed in patients with intracranial vasculopathy and to reduce following successful surgical revascularization. This observation may be attributable to impaired vascular reserve of the ChP or other factors, such as the ChP responding to circulating markers of stress. We extend this work to test the hypothesis that vascular reserve of the ChP is unrelated to intracranial vasculopathy. We performed hypercapnic reactivity (blood oxygenation level-dependent; echo time=35ms; spatial resolution=3.5×3.5×3.5mm, repetition time=2000ms) and catheter angiography assessments of ChP reserve capacity and vascular patency in moyamoya patients (n=53) with and without prior surgical revascularization. Time regression analyses quantified maximum cerebrovascular reactivity and reactivity delay time in ChP and cortical flow territories of major intracranial vessels with steno-occlusion graded as <70%, 70%-99%, and occlusion using Warfarin-Aspirin-Symptomatic-Intracranial-Disease stenosis grading criteria. Analysis of variance (significance: two-sided Bonferroni-corrected p<.05) was applied to evaluate cortical and ChP reactivity, after accounting for end-tidal carbon dioxide change, for differing vasculopathy categories. In patients without prior revascularization, arterial vasculopathy was associated with reduced cortical reactivity and lengthened reactivity delay (p≤.01), as expected. Regardless of surgical history, the ChP reactivity metrics were not significantly related to the degree of proximal stenosis, consistent with ChP reactivity being largely preserved in this population. Findings are consistent with ChP reactivity in moyamoya not being dependent on observed vasculopathy. Future work may investigate the extent to which ChP hyperemia in chronic ischemia reflects circulating markers of glial or ischemic stress.

Impact of Positron Emission Tomographic Myocardial Perfusion Imaging on Patient Selection for Revascularization

BackgroundPositron emission tomography (PET) myocardial perfusion imaging (MPI) quantifies left ventricular ejection fraction (LVEF) at peak stress. PET LVEF reserve (LVEF-R = stress LVEF − rest LVEF) offers diagnostic and prognostic value. ObjectivesThe purpose of this study was to determine if PET LVEF-R identifies patients with survival benefit postrevascularization. MethodsWe followed 14,649 unique consecutive patients undergoing 82Rb rest/stress PET MPI from January 2010 to January 2016 (excluding known cardiomyopathy). Adjusted Cox models were built to predict all-cause death, and the 3-way interaction of known coronary artery disease (CAD) (prior myocardial infarction/revascularization), LVEF-R, and 90-day revascularization was tested. ResultsKnown CAD was present in 4,982 (34.0%). Ischemia was detected in 5,396 (36.8%; ≥10% in 1,909 [13%]). Mean LVEF-R was 4.2% ± 5.7%, and was ≤0, 1 to 5, and >5 in 3,349 (22.9%), 5,266 (35.9%), and 6,034 (41.2%). Over median follow-up of 3.4 years (IQR: 1.9-5.2 years), 1,324 (8.1%) had 90-day revascularization, and there were 2,192 (15.0%) deaths. In multivariable modeling, there was a significant 3-way interaction among known CAD, LVEF-R, and 90-day revascularization (P = 0.025), such that LVEF-R ≤0 identified patients with survival benefit with 90-day revascularization in those without prior CAD (interaction P = 0.005), independently beyond percent ischemia and myocardial flow reserve. Among patients with known CAD, LVEF-R was not prognostic of death (HR: 0.99; 95% CI: 0.98-1.02; P = 0.98). ConclusionsA lack of augmentation or drop in LVEF with vasodilator stress on PET MPI independently identifies patients who have better survival with revascularization within 90 days post-MPI compared with medical therapy, in absence of prior myocardial infarction or revascularization. Multiparametric assessment of ischemia with PET can optimize post-test management.

Vascularized Toe Proximal Interphalangeal Joint Transfer in Posttraumatic Fingers: Analysis of Prognostic Factors for Suboptimal Outcomes.

Posttraumatic finger osteoarthritis of the proximal interphalangeal joint (PIPJ) is a difficult problem. Over the past decade, we have reported several methods for improving the outcomes of vascularized toe joint transfer (VJT). In this study, we focused on determining poor prognostic factors which lead to a suboptimal outcome. A consecutive series of patients with posttraumatic osteoarthritis of the PIPJ who received VJT between January 2008 and January 2021 were enrolled in this study. The senior surgeon (Y.-T.L.) performed the surgery in all cases. In this retrospective study, we reexamine the initial trauma-related soft tissue and bony structure injuries of the recipient finger, to assess the baseline tissue quality before VJT. The injuries were classified into five major categories according to their anatomic region. The functional outcome parameters (including range of motion, percentage of use, and extensor lag of the transferred PIPJ) were collected. Univariate and multivariate linear regression analyses were performed using the generalized estimated equation model to identify the correlation between the injury category involved and functional outcome. A total of 59 digits were enrolled. Our results revealed that the fingers with previous vascular injury that received revascularization procedures had relatively suboptimal functional outcomes. These fingers had a significantly lower percentage of use both before (β = -0.222, P = 0.006) and after (β = -0.177, P = 0.006) receiving secondary procedures to improve functional outcome. Patients with prior revascularization surgery were associated with a poor functional outcome after VJT.

The diagnostic accuracy of two-dimensional strain imaging echocardiography to detect the severity of coronary artery disease in non-ST segment elevation acute coronary syndrome

ObjectiveStrain imaging by two-dimensional speckle tracking echocardiography can detect severe coronary artery disease (CAD). This study aims to assess the diagnostic accuracy of various strain parameters in patients with non-ST segment acute coronary syndrome to detect the angiographic severity of CAD and also to compare among them. MethodsThis hospital-based observational study was conducted on 178 patients with NSTEACS and preserved left ventricular ejection fraction who presented in emergency or outdoor from July 2021 to December 2022. We excluded patients with prior coronary revascularization, heart failure, arrhythmia, more than trivial valvular heart disease, or poor acoustic window. Global longitudinal strain (GLS), peak systolic strain (SS), post systolic index (PSI), and systolic strain rate (SR) were calculated by speckle tracking with automated function imaging. Coronary angiography was done in all patients, and the syntax score was calculated. ResultsThe strain parameters showed a significant correlation with the syntax score. There was a statistically significant difference in strain parameters between patients with left main (LM) or triple vessel disease (TVD) and others. Receiver operating characteristic (ROC) curve analysis showed that GLS had a better diagnostic accuracy for detecting LM or TVD than other strain parameters. GLS with a cut-off value of −11.2% had a sensitivity of 85.7% and specificity of 53.5% for detecting LM or TVD. ConclusionStrain imaging can be a helpful bedside adjunct to conventional investigations for detecting severe CAD in patients with NSTEACS.

Comparison of tirzepatide and dulaglutide on major adverse cardiovascular events in participants with type 2 diabetes and atherosclerotic cardiovascular disease: SURPASS‐CVOT design and baseline characteristics

Tirzepatide, a once-weekly GIP/GLP-1 receptor agonist, reduces blood glucose and body weight in people with type 2 diabetes. The cardiovascular (CV) safety and efficacy of tirzepatide have not been definitively assessed in a cardiovascular outcomes trial. Tirzepatide is being studied in a randomized, double-blind, active-controlled CV outcomes trial. People with type 2 diabetes aged ≥40 years, with established atherosclerotic CV disease, HbA1c ≥7% to ≤10.5%, and body mass index ≥25 kg/m2 were randomized 1:1 to once weekly subcutaneous injection of either tirzepatide up to 15 mg or dulaglutide 1.5 mg. The primary outcome is time to first occurrence of any major adverse cardiovascular event (MACE), defined as CV death, myocardial infarction, or stroke. The trial is event-driven and planned to continue until ≥1,615 participants experience an adjudication-confirmed component of MACE. The primary analysis is noninferiority for time to first MACE of tirzepatide vs dulaglutide by demonstrating an upper confidence limit <1.05, which will also confirm superiority vs a putative placebo, and also to determine whether tirzepatide produces a greater CV benefit than dulaglutide (superiority analysis). Over 2 years, 13,299 people at 640 sites in 30 countries across all world regions were randomized. The mean age of randomized participants at baseline was 64.1 years, diabetes duration 14.7 years, HbA1c 8.4%, and BMI 32.6 kg/m2. Overall, 65.0% had coronary disease, of whom 47.3% reported prior myocardial infarction and 57.4% had prior coronary revascularization. 19.1% of participants had a prior stroke and 25.3% had peripheral artery disease. The trial is fully recruited and ongoing. SURPASS-CVOT will provide definitive evidence as to the CV safety and efficacy of tirzepatide as compared with dulaglutide, a GLP-1 receptor agonist with established CV benefit.