Multivessel Coronary Function Testing Increases Diagnostic Yield in Patients With Angina and Nonobstructive Coronary Arteries.

BACKGROUND: Invasive CFT is the gold standard for diagnosing coronary vasomotor dysfunction in patients with ANOCA. Most institutions recommend only testing the left coronary circulation. Therefore, it is unknown whether testing multiple coronary territories would increase diagnostic yield. OBJECTIVES: The aim of this study was to evaluate the diagnostic yield of multivessel, compared with single-vessel, invasive coronary function testing (CFT) in patients with angina and nonobstructive coronary arteries (ANOCA). METHODS: Multivessel CFT was systematically performed in patients with suspected ANOCA. Vasoreactivity testing was performed using acetylcholine provocation in the left (20 to 200 µg) and right (20 to 80µg) coronary arteries. A pressure-temperature sensor guidewire was used for coronary physiology assessment in all three epicardial vessels. RESULTS: This multicenter study included a total of 228 vessels from 80 patients (57.8 ± 11.8 years of age, 60% women). Compared with single-vessel CFT, multivessel testing resulted in more patients diagnosed with coronary vasomotor dysfunction (86.3% vs 68.8%; P = 0.0005), coronary artery spasm (60.0% vs 47.5%; P = 0.004), and CMD (62.5% vs 36.3%; P < 0.001). Coronary artery spasm (n = 48) predominated in the left coronary system (n = 38), though isolated right coronary spasm was noted in 20.8% (n = 10). Coronary microvascular dysfunction (CMD), defined by abnormal index of microcirculatory resistance and/or coronary flow reserve, was present 62.5% of the cohort (n = 50). Among the cohort with CMD, 27 patients (33.8%) had 1-vessel CMD, 15 patients (18.8%) had 2-vessel CMD, and 8 patients (10%) had 3-vessel CMD. CMD was observed at a similar rate in the territories supplied by all 3 major coronary vessels (left anterior descending coronary artery = 36.3%, left circumflex coronary artery = 33.8%, right coronary artery = 31.3%; P = 0.486). CONCLUSIONS: Multivessel CFT resulted in an increased diagnostic yield in patients with ANOCA compared with single-vessel testing. The results of this study suggest that multivessel CFT has a role in the management of patients with ANOCA.

Paclitaxel-Coated Balloon vs Uncoated Balloon for Coronary In-Stent Restenosis: The AGENT IDE Randomized Clinical Trial.

Importance: Drug-coated balloons offer a potentially beneficial treatment strategy for the management of coronary in-stent restenosis. However, none have been previously evaluated or approved for use in coronary circulation in the United States. Objective: To evaluate whether a paclitaxel-coated balloon is superior to an uncoated balloon in patients with in-stent restenosis undergoing percutaneous coronary intervention. Design, Setting, and Participants: AGENT IDE, a multicenter randomized clinical trial, enrolled 600 patients with in-stent restenosis (lesion length <26 mm and reference vessel diameter >2.0 mm to ≤4.0 mm) at 40 centers across the United States between May 2021 and August 2022. One-year clinical follow-up was completed on October 2, 2023. Interventions: Participants were randomized in a 2:1 allocation to undergo treatment with a paclitaxel-coated (n = 406) or an uncoated (n = 194) balloon. Main Outcomes and Measures: The primary end point of 1-year target lesion failure-defined as the composite of ischemia-driven target lesion revascularization, target vessel-related myocardial infarction, or cardiac death-was tested for superiority. Results: Among 600 randomized patients (mean age, 68 years; 157 females [26.2%]; 42 Black [7%], 35 Hispanic [6%] individuals), 574 (95.7%) completed 1-year follow-up. The primary end point at 1 year occurred in 17.9% in the paclitaxel-coated balloon group vs 28.6% in the uncoated balloon group, meeting the criteria for superiority (hazard ratio [HR], 0.59 [95% CI, 0.42-0.84]; 2-sided P = .003). Target lesion revascularization (13.0% vs 24.7%; HR, 0.50 [95% CI, 0.34-0.74]; P = .001) and target vessel-related myocardial infarction (5.8% vs 11.1%; HR, 0.51 [95% CI, 0.28-0.92]; P = .02) occurred less frequently among patients treated with paclitaxel-coated balloon. The rate of cardiac death was 2.9% vs 1.6% (HR, 1.75 [95% CI, 0.49-6.28]; P = .38) in the coated vs uncoated balloon groups, respectively. Conclusions and Relevance: Among patients undergoing coronary angioplasty for in-stent restenosis, a paclitaxel-coated balloon was superior to an uncoated balloon with respect to the composite end point of target lesion failure. Paclitaxel-coated balloons are an effective treatment option for patients with coronary in-stent restenosis. Trial Registration: ClinicalTrials.gov Identifier: NCT04647253.

Comprehensive Management of ANOCA, Part 1-Definition, Patient Population, and Diagnosis: JACC State-of-the-Art Review.

Angina with nonobstructive coronary arteries (ANOCA) is increasingly recognized and may affect nearly one-half of patients undergoing invasive coronary angiography for suspected ischemic heart disease. This working diagnosis encompasses coronary microvascular dysfunction, microvascular and epicardial spasm, myocardial bridging, and other occult coronary abnormalities. Patients with ANOCA often face a high burden of symptoms and may experience repeated presentations to multiple medical providers before receiving a diagnosis. Given the challenges of establishing a diagnosis, patients with ANOCA frequently experience invalidation and recidivism, possibly leading to anxiety and depression. Advances in scientific knowledge and diagnostic testing now allow for routine evaluation of ANOCA noninvasively and in the cardiac catheterization laboratory with coronary function testing (CFT). CFT includes diagnostic coronary angiography, assessment of coronary flow reserve and microcirculatory resistance, provocative testing for endothelial dysfunction and coronary vasospasm, and intravascular imaging for identification of myocardial bridging, with hemodynamic assessment as needed.

Comprehensive Management of ANOCA, Part 2-Program Development, Treatment, and Research Initiatives: JACC State-of-the-Art Review.

Centers specializing in coronary function testing are critical to ensure a systematic approach to the diagnosis and treatment of angina with nonobstructive coronary arteries (ANOCA). Management leveraging lifestyle, pharmacology, and device-based therapeutic options for ANOCA can improve angina burden and quality of life in affected patients. Multidisciplinary care teams that can tailor and titrate therapies based on individual patient needs are critical to the success of comprehensive programs. As coronary function testing for ANOCA is more widely adopted, collaborative research initiatives will be fundamental to improve ANOCA care. These efforts will require standardized symptom assessments and data collection, which will propel future large-scale clinical trials.

Prevention of Cardiovascular Disease in Women With Pregnancy-Related Risk Factors: A Prospective Women's Heart Clinic Study.

Background Hypertensive disorders of pregnancy, gestational diabetes, and having a small-for-gestational-age baby are known to substantially increase a woman's risk of cardiovascular disease. Despite this, evidence for models of care that mitigate cardiovascular disease risk in women with these pregnancy-related conditions is lacking. Methods and Results A 6-month prospective cohort study assessed the effectiveness of a multidisciplinary Women's Heart Clinic on blood pressure and lipid control in women aged 30 to 55 years with a past pregnancy diagnosis of hypertensive disorders of pregnancy, gestational diabetes, or a small-for-gestational age baby in Melbourne, Australia. The co-primary end points were (1) blood pressure <140/90 mm Hg or <130/80 mm Hg if diabetes and (2) total cholesterol to high-density lipoprotein cholesterol ratio <4.5. The study recruited 156 women with a mean age of 41.0±4.2 years, 3.9±2.9 years from last delivery, 68.6% White, 20.5% South/East Asian, and 80.5% university-educated. The proportion meeting blood pressure target increased (69.2% to 80.5%, P=0.004), with no significant change in lipid targets (80.6% to 83.7%, P=0.182). Systolic blood pressure (-6.9 mm Hg [95% CI, -9.1 to -4.7], P<0.001), body mass index (-0.6 kg/m2 [95% CI, -0.8 to -0.3], P<0.001), low-density lipoprotein cholesterol (-4.2 mg/dL [95% CI, -8.2 to -0.2], P=0.042), and total cholesterol (-4.6 mg/dL [95% CI, -9.1 to -0.2] P=0.042) reduced. Heart-healthy lifestyle significantly improved with increased fish/olive oil (36.5% to 51.0%, P=0.012), decreased fast food consumption (33.8% to 11.0%, P<0.001), and increased physical activity (84.0% to 92.9%, P=0.025). Conclusions Women at high risk for cardiovascular disease due to past pregnancy-related conditions experienced significant improvements in multiple cardiovascular risk factors after attending a Women's Heart Clinic, potentially improving long-term cardiovascular disease outcomes. Registration URL: https://www.anzctr.org.au; Unique identifier: ACTRN12622000646741.

Symptomatic Myocardial Bridging in D-Transposition of the Great Arteries Post-Arterial Switch.

We present Stanford's experience with patients post-arterial switch operation presenting with chest pain found to have hemodynamically significant myocardial bridging. The evaluation of symptomatic patients post-arterial switch should not only include assessment for coronary ostial patency but also for nonobstructive coronary conditions such as myocardial bridging. (Level of Difficulty: Advanced.).

Impact of myocardial bridging on coronary artery plaque formation and long-term mortality after heart transplantation.

OBJECTIVES: This study aimed to explore the impact of myocardial bridging (MB) on early development of cardiac allograft vasculopathy and long-term graft survival after heart transplantation. BACKGROUND: MB has been reported to be associated with acceleration of proximal plaque development and endothelial dysfunction in native coronary atherosclerosis. However, its clinical significance in heart transplantation remains unclear. METHODS: In 103 heart-transplant recipients, serial (baseline and 1-year post-transplant) volumetric intravascular ultrasound (IVUS) analyses were performed in the first 50 mm of the left anterior descending (LAD) artery. Standard IVUS indices were evaluated in 3 equally divided LAD segments (proximal, middle, and distal segments). MB was defined by IVUS as an echolucent muscular band lying on top of the artery. The primary endpoint was death or re-transplantation, assessed for up to 12.2 years (median follow-up: 4.7 years). RESULTS: IVUS identified MB in 62% of the study population. At baseline, MB patients had smaller intimal volume in the distal LAD than non-MB patients (p = 0.002). During the first year, vessel volume decreased diffusely irrespective of the presence of MB. Intimal growth diffusely distributed in non-MB patients, whereas MB patients demonstrated significantly augmented intimal formation in the proximal LAD. Kaplan-Meier analysis revealed significantly lower event-free survival in patients with versus without MB (log-rank p = 0.02). In multivariate analysis, the presence of MB was independently associated with late adverse events [hazard ratio 5.1 (1.6-22.2)]. CONCLUSION: MB appears to relate to accelerated proximal intimal growth and reduced long-term survival in heart-transplant recipients.

Association of Neighborhood Income with Clinical Outcomes Among Pregnant Patients with Cardiac Disease.

Cardiovascular disease is the leading cause of pregnancy mortality. Socioeconomic and racial disparities in pregnancy are well established. Despite this, little is known about the impact of social determinants of health in pregnant patients with heart disease. This study aims to determine whether pregnant patients with heart disease living in lower income neighborhoods and managed at cardio-obstetrics programs have higher rates of cardiac events or preterm deliveries compared with those living in higher income neighborhoods. This is a retrospective cohort study of 206 patients between 2010 and 2020 at a quaternary care hospital in Northern California. The exposure was household income level based on neighborhood defined by the US Census data. Patients in lower income neighborhoods (N = 103) were 45% Hispanic, 34% White, and 14% Asian versus upper income neighborhoods (N = 103), which were 48% White, 31% Asian, and 12% Hispanic (p < 0.001). There was no significant difference in the rates of intrapartum cardiac events (10% vs. 4%; p = 0.16), postpartum cardiac events (14% vs. 17%; p = 0.7), and preterm delivery (24% vs. 17%; p = 0.23). The rates of antepartum hospitalization were higher for lower income neighborhoods (42% vs 22%; p = 0.004). While there is no significant difference in cardiac events and preterm delivery rates between patients from low versus high income neighborhoods, patients from lower income neighborhoods have higher antepartum hospitalization rates. Earlier identification of clinical deterioration provided by a cardio-obstetrics team may contribute to increased hospitalizations, which might mitigate socioeconomic disparities in outcomes for these pregnant patients with heart disease.

Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.

BACKGROUND: Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm. OBJECTIVES: We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols. METHODS: PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock. RESULTS: A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 µg and 200 µg. CONCLUSIONS: Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.

Colocalization of Coronary Plaque with Wall Shear Stress in Myocardial Bridge Patients.

PURPOSE: Patients with myocardial bridges (MBs) have a higher prevalence of atherosclerosis. Wall shear stress (WSS) has previously been correlated with plaque in coronary artery disease patients, but such correlations have not been investigated in symptomatic MB patients. The aim of this paper was to use a multi-scale computational fluid dynamics (CFD) framework to simulate hemodynamics in MB patient, and investigate the co-localization of WSS and plaque. METHODS: We identified N = 10 patients from a previously reported cohort of 50 symptomatic MB patients, all of whom had plaque in the proximal vessel. Dynamic 3D models were reconstructed from coronary computed tomography angiography (CCTA), intravascular ultrasound (IVUS) and catheter angiograms. CFD simulations were performed to compute WSS proximal to, within and distal to the MB. Plaque was quantified from IVUS images in 2 mm segments and registered to CFD model. Plaque area was compared to absolute and patient-normalized WSS. RESULTS: WSS was lower in the proximal segment compared to the bridge segment (6.1 ± 2.9 vs. 16.0 ± 7.1 dynes/cm2, p value < 0.01). Plaque area and plaque burden measured from IVUS peaked at 1-3 cm proximal to the MB entrance, coinciding with the first diagonal branch. Normalized WSS showed a statistically significant moderate correlation with plaque area (r = 0.41, p < 0.01). CONCLUSION: WSS may be obtained non-invasively in MB patients and provides a surrogate marker of plaque area. Using CFD, it may be possible to non-invasively assess the extent of plaque area, and identify patients who could benefit from frequent monitoring or medical management.

Relationship Between Coronary Atheroma, Epicardial Adipose Tissue Inflammation, and Adipocyte Differentiation Across the Human Myocardial Bridge.

Background Inflammation in epicardial adipose tissue (EAT) may contribute to coronary atherosclerosis. Myocardial bridge is a congenital anomaly in which the left anterior descending coronary artery takes a "tunneled" course under a bridge of myocardium: while atherosclerosis develops in the proximal left anterior descending coronary artery, the bridged portion is spared, highlighting the possibility that geographic separation from inflamed EAT is protective. We tested the hypothesis that inflammation in EAT was related to atherosclerosis by comparing EAT from proximal and bridge depots in individuals with myocardial bridge and varying degrees of atherosclerotic plaque. Methods and Results Maximal plaque burden was quantified by intravascular ultrasound, and inflammation was quantified by pericoronary EAT signal attenuation (pericoronary adipose tissue attenuation) from cardiac computed tomography scans. EAT overlying the proximal left anterior descending coronary artery and myocardial bridge was harvested for measurement of mRNA and microRNA (miRNA) using custom chips by Nanostring; inflammatory cytokines were measured in tissue culture supernatants. Pericoronary adipose tissue attenuation was increased, indicating inflammation, in proximal versus bridge EAT, in proportion to atherosclerotic plaque. Individuals with moderate-high versus low plaque burden exhibited greater expression of inflammation and hypoxia genes, and lower expression of adipogenesis genes. Comparison of gene expression in proximal versus bridge depots revealed differences only in participants with moderate-high plaque: inflammation was higher in proximal and adipogenesis lower in bridge EAT. Secreted inflammatory cytokines tended to be higher in proximal EAT. Hypoxia-inducible factor 1a was highly associated with inflammatory gene expression. Seven miRNAs were differentially expressed by depot: 3192-5P, 518D-3P, and 532-5P were upregulated in proximal EAT, whereas miR 630, 575, 16-5P, and 320E were upregulated in bridge EAT. miR 630 correlated directly with plaque burden and inversely with adipogenesis genes. miR 3192-5P, 518D-3P, and 532-5P correlated inversely with hypoxia/oxidative stress, peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG1a), adipogenesis, and angiogenesis genes. Conclusions Inflammation is specifically elevated in EAT overlying atherosclerotic plaque, suggesting that EAT inflammation is caused by atherogenic molecular signals, including hypoxia-inducible factor 1a and/or miRNAs in an "inside-to-out" relationship. Adipogenesis was suppressed in the bridge EAT, but only in the presence of atherosclerotic plaque, supporting cross talk between the vasculature and EAT. miR 630 in EAT, expressed differentially according to burden of atherosclerotic plaque, and 3 other miRNAs appear to inhibit key genes related to adipogenesis, angiogenesis, hypoxia/oxidative stress, and thermogenesis in EAT, highlighting a role for miRNA in mediating cross talk between the coronary vasculature and EAT.

Impact of Diastolic Vessel Restriction on Quality of Life in Symptomatic Myocardial Bridging Patients Treated With Surgical Unroofing: Preoperative Assessments With Intravascular Ultrasound and Coronary Computed Tomography Angiography.

[Figure: see text].

Abnormal shear stress and residence time are associated with proximal coronary atheroma in the presence of myocardial bridging.

BACKGROUND: Atheromatous plaques tend to form in the coronary segments proximal to a myocardial bridge (MB), but the mechanism of this occurrence remains unclear. This study evaluates the relationship between blood flow perturbations and plaque formation in patients with an MB. METHODS AND RESULTS: A total of 92 patients with an MB in the mid left anterior descending artery (LAD) and 20 patients without an MB were included. Coronary angiography, intravascular ultrasound, and coronary physiology measurements were performed. A moving-boundary computational fluid dynamics algorithm was used to derive wall shear stress (WSS) and peak residence time (PRT). Patients with an MB had lower WSS (0.46 ± 0.21 vs. 0.96 ± 0.33 Pa, p < 0.001) and higher maximal plaque burden (33.6 ± 15.0 vs. 14.2 ± 5.8%, p < 0.001) within the proximal LAD compared to those without. Plaque burden in the proximal LAD correlated significantly with proximal WSS (r = -0.51, p < 0.001) and PRT (r = 0.60, p < 0.001). In patients with an MB, the site of maximal plaque burden occurred 23.4 ± 13.3 mm proximal to the entrance of the MB, corresponding to the site of PRT. CONCLUSIONS: Regions of low WSS and high PRT occur in arterial segments proximal to an MB, and this is associated with the degree and location of coronary atheroma formation.

Preliminary Support for Group Cognitive Behavioral Therapy (CBT) to Reduce Psychological Distress in Patients with Spontaneous Coronary Artery Dissection (SCAD).

Spontaneous coronary artery dissection (SCAD) can occur as an atypical cause of myocardial infarction. Preliminary evidence suggests that SCAD patients experience high rates of post-event psychological distress. It is unknown whether psychosocial interventions may reduce the distress burden. Seven SCAD patients (mean age = 53.3 years) completed a CBT-based support group. All seven participants completed measures for anxiety, depression, and cardiac-related quality of life at baseline and post-intervention, and five participants completed measures at 3-month follow-up. Six of 7 participants scored above the clinical threshold on a measure of anxiety at baseline and posttreatment. At follow-up, 3 of 5 participants scored below the clinical threshold. For depression, 3 of 7 reported elevated depressive symptoms at baseline. By follow-up, 1 of 5 endorsed elevated depressive symptoms. This is the first known psychosocial intervention study of patients with SCAD. Anxiety symptoms improved for most patients by follow-up with some patients having improved depressive symptoms. Although the sample size is limited, this pilot study suggests a potential benefit of group psychosocial interventions for SCAD survivors.