Determining the Cause of Coronary Vasomotor Disorders in Patients With Ischemia and Nonobstructive Coronary Arteries: Design and Rationale of the DISCOVER INOCA Prospective, Multicenter Registry.

Background: Approximately 30% to 50% of patients who are referred for diagnostic coronary angiography are found to have no obstructive coronary artery disease (CAD). Ischemia and nonobstructive coronary arteries (INOCA) is increasingly recognized and encompasses coronary microvascular dysfunction, vasospastic angina, symptomatic myocardial bridging, and other vasomotor disorders. However, the prevalence of these disorders and whether underlying atherosclerotic plaque burden and morphology affect the long-term outcomes of each physiologic phenotype is unknown. Methods: The DISCOVER INOCA registry is ongoing at 8 centers in the United States and plans to enroll 500 patients with ischemic heart disease referred for angiography undergoing coronary function testing (CFT). All participants will complete patient-reported outcome measures and undergo protocol-guided angiography, acetylcholine provocation, coronary thermodilution, and intravascular imaging. Follow-up assessments occur at 30 days, 6 months, 1 year, and annually for 5 years. The primary short-term end point is the prevalence of INOCA phenotypes based on physiology and the degree of atherosclerosis based on intravascular ultrasound or optical coherence tomography (intravascular imaging). The primary long-term end point is the incidence of major adverse cardiovascular events, defined as a composite of cardiovascular death, myocardial infarction, hospitalization for cardiovascular causes, or coronary revascularization at a follow-up of 5 years. At the time of this publication, 100 participants have been enrolled. Conclusions: DISCOVER INOCA is the first prospective study of INOCA patients to integrate anatomic and physiologic measures of disease and correlate them with long-term outcomes. DISCOVER INOCA will report on the prevalence of INOCA phenotypes, the safety of comprehensive invasive CFT, and the impact of testing on diagnoses and medical therapy. Symptoms and cardiovascular adverse events at long-term follow-up will be determined in patients with no obstructive CAD undergoing angiography.

Comparison among various physiology and angiography-guided strategies for deferring percutaneous coronary intervention: A network meta-analysis.

BACKGROUND/PURPOSE: It is unclear whether coronary physiology or coronary angiography (CA)-guided strategy is the more preferable approach for deferring percutaneous coronary intervention (PCI). We sought to evaluate the clinical efficacy of various PCI strategies through a network meta-analysis of randomized controlled trials (RCTs). METHODS/MATERIALS: We searched multiple databases for RCTs investigating the impact of the following strategies for the purpose of determining whether or not to defer PCI: fractional flow reserve, instantaneous wave-free ratio, quantitative flow ratio (QFR), and CA. We conducted a network meta-analysis for trial-defined major adverse cardiovascular events (MACE), all-cause death, cardiovascular death, myocardial infarction (MI), target lesion revascularization (TLR), and stent thrombosis. We performed a subgroup analysis for those with acute coronary syndrome (ACS). RESULTS: Our search identified 12 eligible RCTs including a total of 13,177 patients. QFR-guided PCI was associated with reduced MACE, MI, and TLR compared with CA-guided PCI (relative risk (RR) 0.68; 95 % confidence interval (CI] [0.49 to 0.94], RR 0.58; 95 % CI [0.36 to 0.96], and RR 0.58; 95 % CI [0.38 to 0.91], respectively). There were no significant differences in any pairs for all-cause death, cardiovascular death, or stent thrombosis. QFR was ranked the best in most outcomes. In the subgroup analysis of the ACS cohort, there were no significant differences in MACE between any comparisons. CONCLUSIONS: QFR was associated with reduced MACE, MI, and TLR compared with CA, and ranked the best in most outcomes. However, this was not applied in the ACS cohort.

Neutrophil-to-lymphocyte ratio and prognosis in patients undergoing percutaneous coronary intervention for acute coronary syndrome.

OBJECTIVE: The purpose of this study was to characterize Acute Coronary Syndrome (ACS)-associated inflammation by investigating correlates of the neutrophil-to-lymphocyte ratio (NLR), a surrogate marker of inflammation, and its relation to 1-year mortality in a cohort of patients undergoing percutaneous coronary intervention (PCI) for ACS at a single institution. METHODS: We performed a single-institution, retrospective, observational study of all-comer ACS patients who underwent PCI and were discharged home before the COVID-19 pandemic between September 23, 2011 and July 31, 2017 for who outcomes data were available. RESULTS: NLRhigh group tended to be older, white patients, less likely to smoke, more likely to have a history of heart failure and cardiac arrest, higher creatinine values, lower LVEF, and higher CK-MB (a surrogate for infarct size). Linear regression model demonstrated a strong correlation between increasing NLR and white race (B = 1.103, p = 0.001, hemoglobin (B = -0.30, p < 0.001), peak CK-MB (B = 0.004, p = 0.02), LVEF (B = -0.048, p < 0.001), and serum creatinine (B = 0.47, p = 0.03). There were a total of 87 deaths at one year. NLR > 3.4 was associated with worse one-year survival post-PCI (91.4 % vs. 95.4 %, log-rank p < 0.004), which was confirmed on multivariate analysis. CONCLUSION: Our data confirm the independent prognostic significance of inflammation to mortality after ACS and may provide some insight into the putative benefits of inflammation modulation.

Diagnostic performances of Nonhyperemic Pressure Ratios and Coronary Angiography-Based Fractional Flow Reserve against conventional Wire-Based Fractional Flow Reserve.

BACKGROUND: Nonhyperemic pressure ratios (NHPRs) have been proposed as alternatives to fractional flow reserve (FFR) without induction of hyperemia. More recently, imaging based-FFR estimation, especially coronary angiography-derived FFR (Angio-FFR) measurement, is proposed to estimate wire-based FFR. However, little is known about the diagnostic performance of these indices against conventional FFR. AIMS: We aimed to assess and compare the diagnostic performance of both NHPRs and coronary Angio-FFR against wire-based conventional FFR. METHODS: PubMed and Embase databases were systematically searched for peer-reviewed original articles up to 08/2022. The primary outcomes were the pooled sensitivity and specificity as well as the area under the curve (AUC) of the summary receiver-operating characteristic curve of those indices. RESULTS: A total of 6693 records were identified after a literature search, including 37 reports for NHPRs and 34 for Angio-FFR. Overall, NHPRs have a lower diagnostic performance in estimating wire-based FFR with an AUC of 0.85 (0.81, 0.88) when compared with Angio-FFR of 0.95 (0.93, 0.97). When all four modalities of NHPRs (iFR, Pd/Pa, DPR, RFR) were compared, those had overlapping AUCs without major differences among each other. Similarly, when the two most commonly used Angio-FFR (QFR, FFR angio ) were compared, those had overlapping AUCs without major differences among each other. CONCLUSION: Angio-FFR may offer a better estimation of wire-based FFR than NHPRs. Our results support a wider use of Angio-FFR in the cardiac catheterization laboratory to streamline our workflow for coronary physiologic assessment. CLASSIFICATIONS: FFR,, stable ischemic disease and non-ST elevation acute coronary syndrome.

Outcomes Based on Angiographic vs Functional Significance of Complex 3-Vessel Coronary Disease: FAME 3 Trial.

BACKGROUND: The functional SYNTAX score (FSS), which incorporates functional information as assessed by fractional flow reserve (FFR), is a better predictor of outcome after percutaneous coronary intervention (PCI) in patients with less complex coronary artery disease (CAD). OBJECTIVES: This study sought to test the prognostic value of the FSS in patients with complex CAD eligible for coronary artery bypass grafting (CABG). METHODS: The FAME 3 (Fractional Flow Reserve Versus Angiography for Multivessel Evaluation 3) trial compared FFR-guided PCI with CABG in patients with angiographic 3-vessel CAD. In this prespecified substudy, the angiographic core laboratory calculated the SYNTAX score (SS) and then the FSS by eliminating lesions that were not significant based on FFR. Outcomes in the PCI patients based on the FSS and the SS were compared to each other and to the patients treated with CABG. RESULTS: The FSS reclassified more than one-quarter of patients from an SS >22 to an FSS ≤22. In the 50% of PCI patients who had an FSS ≤22, the primary endpoint occurred at a similar rate to patients treated with CABG (P = 0.77). The primary endpoint in patients without functionally significant 3-vessel CAD was similar to the CABG group (P = 0.97). The rate of myocardial infarction and revascularization among all deferred lesions was 0.5% and 3.2%, respectively. CONCLUSIONS: By measuring the FSS, one can identify 50% of patients who have a similar outcome at 1 year with PCI compared with CABG. Lesions deferred from PCI based on FFR have a low event rate.

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.

Challenge in Diagnosis and Management of a Patient With Myocardial Bridge and Coronary Artery Spasm.

Positive ischemia by noninvasive imaging studies often results in nonobstructive disease in cardiac catheterization. In this case, we observed ischemia by nuclear stress test in only the anteroseptal area, and the apex is free of ischemia. Coronary angiogram findings were unremarkable, but intravascular ultrasound confirmed the long length of the myocardial bridge. Further testing with spasm provocation and microvascular testing showed diffuse epicardial spasm in this area of myocardial bridge without microvascular dysfunction. We observed the myocardial bridge but no microvascular dysfunction. This case illustrates the coexistence of spasm in the area of a myocardial bridge and the challenges in the medical management of these patients. (Level of Difficulty: Advanced.).

Fractional Flow Reserve-Guided PCI or Coronary Bypass Surgery for 3-Vessel Coronary Artery Disease: 3-Year Follow-Up of the FAME 3 Trial.

BACKGROUND: Previous studies comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with multivessel coronary disease not involving the left main have shown significantly lower rates of death, myocardial infarction (MI), or stroke after CABG. These studies did not routinely use current-generation drug-eluting stents or fractional flow reserve (FFR) to guide PCI. METHODS: FAME 3 (Fractional Flow Reserve versus Angiography for Multivessel Evaluation) is an investigator-initiated, multicenter, international, randomized trial involving patients with 3-vessel coronary artery disease (not involving the left main coronary artery) in 48 centers worldwide. Patients were randomly assigned to receive FFR-guided PCI using zotarolimus drug-eluting stents or CABG. The prespecified key secondary end point of the trial reported here is the 3-year incidence of the composite of death, MI, or stroke. RESULTS: A total of 1500 patients were randomized to FFR-guided PCI or CABG. Follow-up was achieved in >96% of patients in both groups. There was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI compared with CABG (12.0% versus 9.2%; hazard ratio [HR], 1.3 [95% CI, 0.98-1.83]; P=0.07). The rates of death (4.1% versus 3.9%; HR, 1.0 [95% CI, 0.6-1.7]; P=0.88) and stroke (1.6% versus 2.0%; HR, 0.8 [95% CI, 0.4-1.7]; P=0.56) were not different. MI occurred more frequently after PCI (7.0% versus 4.2%; HR, 1.7 [95% CI, 1.1-2.7]; P=0.02). CONCLUSIONS: At 3-year follow-up, there was no difference in the incidence of the composite of death, MI, or stroke after FFR-guided PCI with current-generation drug-eluting stents compared with CABG. There was a higher incidence of MI after PCI compared with CABG, with no difference in death or stroke. These results provide contemporary data to allow improved shared decision-making between physicians and patients with 3-vessel coronary artery disease. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02100722.

Early optical coherence tomography evaluation of donor-transmitted atherosclerosis and cardiac allograft vasculopathy: insights from a prospective, single-center study.

BACKGROUND: The impact of donor transmitted atherosclerosis as assessed by intravascular ultrasound on development and progression of cardiac allograft vasculopathy (CAV) after heart transplantation (HT) remains poorly defined in contemporary practice. In this exploratory analysis, we sought to assess the prognostic role of early qualitative assessment of donor artery morphology using optical coherence tomography (OCT) as a more sensitive imaging modality. METHODS: HT recipients were prospectively enrolled for baseline OCT imaging of the left anterior descending coronary artery. OCT findings were classified as normal, homogeneous intimal thickening, and advanced plaque characteristics. The endpoint was a composite of cardiac death, myocardial infarction, or new angiographically detectable CAV stratified by the International Society of Heart and Lung Transplantation criteria up to 4 years of follow-up. RESULTS: A total of 35 patients underwent baseline OCT of whom 51.4% had normal OCT, 14.3% had homogenous plaque, and 34.3% had advanced characteristics. There were no significant differences in baseline demographics between patients with and without normal morphology. During a mean follow-up of 3.3 ± 0.4 years, the endpoint occurred in 11 patients including 1 death, 7 CAV1, 3 CAV2, and 1 CAV3. Kaplan-Meier analysis revealed a significantly higher event rate in patients with advanced characteristics (log-rank p = 0.010). In multivariate analysis, OCT-based plaque morphology was an independent predictor of clinical events (adjusted hazard ratio 4.57, 95% confidence interval 1.50-13.92, p = 0.008) while maximal intimal thickness ≥0.5 mm was not. CONCLUSIONS: Early qualitative OCT assessment of donor coronary artery morphology appears to be a reliable marker for predicting future cardiovascular events in HT recipients. Our findings warrant more careful study in a larger cohort.

Nonhyperemic Pressure Ratios-All the Same or Nuanced Differences?

Fractional flow reserve (FFR) has become the gold standard for invasively assessing the functional significance of coronary artery disease (CAD) to guide revascularization. The amount of evidence supporting the role of FFR in the cardiac catheterization laboratory is large and still growing. However, FFR uptake in the daily practice is limited by a variety of factors such as invasive instrumentation of the coronary artery that requires extra time and need for vasodilator medications for hyperemia. In this review, we describe the details of wire-based alternatives to FFR, providing insights as to their development, clinical evidence, and limitations.

Impact of Frailty on Outcomes After Transcatheter Edge-to-Edge Repair With MitraClip (from the National Inpatient Sample Database).

Transcatheter edge-to-edge repair (TEER) with MitraClip (Abbott, Santa Clara, California) is a frequently chosen method for mitral valve repair for patients at high surgical risk. We investigated the impact of frailty on outcomes of patients who underwent TEER. We reviewed the National Inpatient Sample to identify patients that underwent TEER with MitraClip. Frailty was defined using the Johns Hopkins Adjusted Clinical Groups frailty-defining diagnoses indicator. The primary end point was in-hospital mortality. The secondary end points included blood transfusion, respiratory failure, sepsis, length of stay, and total hospitalization cost. Univariate and multivariate logistic regression analyses were performed to determine any association between frailty and primary or secondary outcomes. From January 2016 to December 2017, 10,055 patients underwent TEER in the United States, and 10.6% of them met the criteria for frailty. The frail group showed increased in-hospital mortality (7.04% vs 1.61%, p <0.001) and respiratory failure (3.75% vs 0.95%, p <0.001). Similarly, the frail group had longer lengths of stay (6 vs 2 days, p <0.001) and higher hospitalization costs ($224.8k vs $180.9k, p <0.001). After multivariable logistic regression analysis, frailty was associated with increased in-hospital mortality (odds ratio [OR] 3.70, 95% confidence interval [CI] 1.91 to 7.18, p <0.001), transfusion (OR 1.85, 95% CI 1.07 to 3.19, p = 0.029), respiratory failure (OR 3.56, 95% CI 1.48 to 8.52, p = 0.005), and sepsis (OR 4.17, 95% CI 1.84 to 9.46, p = 0.001). In conclusion, frailty was present in about 10% of patients who underwent TEER from 2016 to 2017. The presence of frailty was associated with worse in-hospital outcomes and greater resource use.

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.