Functional coronary angiography in symptomatic patients with no obstructive coronary artery disease.

BACKGROUND: Patients without obstructive coronary artery disease (CAD) may have epicardial or microvascular dysfunction. The purpose of this study was to characterize patterns of epicardial and microvascular dysfunction in men and women with stable and unstable angina undergoing functional coronary angiography to inform medical therapy. METHODS: 163 symptomatic patients with ≤50% diameter stenosis and fractional flow reserve (FFR) > 0.8 underwent endothelium-dependent epicardial and microvascular function after intracoronary acetylcholine (10-4  M, 81 mcg over 3 minutes). Endothelium-independent function was assessed using coronary flow reserve (CFR) and hyperemic microvascular resistance (HMR) after intravenous adenosine (140 ug/kg/min). Coronary microvascular dysfunction (CMD) was defined as CFR < 2.5, HMR ≥2, or ≤50% change in coronary blood flow with acetylcholine (CBFACH ). RESULTS: Seventy-two percent had endothelial-dependent epicardial dysfunction (response to ACH: % ∆ in coronary artery diameter and ∆%CBFACH ) and 92% had CMD. Among CMD patients, 65% had CFR < 2.5, 35% had HMR ≥2, and 60% had CBFACH change ≤50%. CFR modestly correlated with HMR (r = -0.38, p < .0001). Among patients with normal CFR, 26% had abnormal epicardial and 20% had abnormal microvascular endothelial dysfunction. Women had a lower CFR (p = .02), higher FFR (p = .03) compared to men. There were no differences in epicardial and microvascular function between patients with stable and unstable angina. CONCLUSION: In patients with no obstructive CAD: CMD is prevalent, abnormal CFR does not correlate with epicardial or microvascular endothelial dysfunction, women have lower CFR, higher FFR but similar endothelial function compared to men.

State of the Art: Imaging for Myocardial Viability: A Scientific Statement From the American Heart Association.

A substantial proportion of patients with acute myocardial infarction develop clinical heart failure, which remains a common and major healthcare burden. It has been shown that in patients with chronic coronary artery disease, ischemic episodes lead to a global pattern of cardiomyocyte remodeling and dedifferentiation, hallmarked by myolysis, glycogen accumulation, and alteration of structural proteins. These changes, in conjunction with an impaired global coronary reserve, may eventually become irreversible and result in ischemic cardiomyopathy. Moreover, noninvasive imaging of myocardial scar and hibernation can inform the risk of sudden cardiac death. Therefore, it would be intuitive that imaging of myocardial viability is an essential tool for the proper use of invasive treatment strategies and patient prognostication. However, this notion has been challenged by large-scale clinical trials demonstrating that, in the modern era of improved guideline-directed medical therapies, imaging of myocardial viability failed to deliver effective guidance of coronary bypass surgery to a reduction of adverse cardiac outcomes. In addition, current available imaging technologies in this regard are numerous, and they target diverse surrogates of structural or tissue substrates of myocardial viability. In this document, we examine these issues in the current clinical context, collect current evidence of imaging technology by modality, and inform future directions.

New-Onset Uncontrolled Hypertension and Renal Failure in a Young Woman.

This report describes the case of a previously healthy 30-year-old woman who presented with uncontrolled hypertension and renal failure. This case emphasizes the importance of considering renal artery disease. The differential diagnosis for renal artery stenosis is discussed, and the diagnosis and management of Takayasu's arteritis in this patient are highlighted. (Level of Difficulty: Beginner.).

Percutaneous coronary intervention or coronary artery bypass grafting for unprotected left main coronary artery disease.

BACKGROUND: Recent trials comparing PCI with CABG for unprotected left main disease yielded discrepant evidence. OBJECTIVES: To perform an updated meta-analysis of randomized trials comparing percutaneous coronary intervention (PCI) with coronary artery bypass grafting (CABG) in patients with unprotected left main coronary artery disease. METHODS: Randomized trials comparing PCI versus CABG for patients with unprotected left main coronary artery disease were included. Summary estimates risk ratios (RRs) were performed with a DerSimonian and Laird model at short-term, intermediate and long-term follow-up periods (i.e., 30-days, 1-year, and >1-year). Outcomes evaluated were major adverse cardiac and cerebrovascular events (MACCE), all-cause mortality, myocardial infarction, stroke, revascularization and stent thrombosis or symptomatic graft occlusion. RESULTS: Six trials with 4,700 patients and a mean SYNTAX score of 23 were included. At short-term follow-up, the risk of MACCE was lower with PCI (RR 0.55, 95% confidence interval [CI] 0.39-0.76) driven by the lower risk of myocardial infarction (RR 0.67, 95% CI 0.46-0.99), and stroke (RR 0.38, 95% CI 0.16-0.90). The risk of MACCE was similar at the intermediate follow-up (RR 1.21, 95% CI 0.97-1.51). At long-term follow-up, PCI was associated with a higher risk of MACCE (RR 1.19, 95% CI 1.01-1.41), due to a higher risk of revascularization (RR 1.62, 95% CI 1.34-1.94), while the risk of all-cause mortality, myocardial infarction, and stroke were similar. CONCLUSIONS: In patients with unprotected left main coronary disease and low to intermediate SYNTAX score, PCI might be an acceptable alternative to CABG. © 2017 Wiley Periodicals, Inc.

Fractional flow reserve for the assessment of complex multivessel disease in a patient after hybrid coronary revascularization.

We present a case of a 43-year-old woman with history of hybrid coronary revascularization [endoscopic atraumatic coronary artery bypass (ACAB)] of left internal mammary artery (LIMA) to the left anterior descending artery (LAD) and stent implantation in right coronary artery (RCA), who presented 6 years later with recurrent atypical angina. Coronary angiography revealed patent LIMA to LAD and RCA stent, with a new lesion in an obtuse marginal artery and significant progression of disease in the proximal/mid LAD proximal to LIMA touchdown. To further evaluate the hemodynamic significance of these new disease segments, the patient underwent fractional flow reserve (FFR) assessment of the left coronary system with subsequent stent implantation in the proximal/mid LAD. This case illustrates (1) the critical value of FFR assessment in determining the ischemia provoking lesions in this post ACAB patient with complex multivessel coronary artery disease; and (2) the accelerated progression of atherosclerosis in bypassed segments as compared to segments proximal to stents.

Coronary artery wall shear stress is associated with progression and transformation of atherosclerotic plaque and arterial remodeling in patients with coronary artery disease.

BACKGROUND: Experimental studies suggest that low wall shear stress (WSS) promotes plaque development and high WSS is associated with plaque destabilization. We hypothesized that low-WSS segments in patients with coronary artery disease develop plaque progression and high-WSS segments develop necrotic core progression with fibrous tissue regression. METHODS AND RESULTS: Twenty patients with coronary artery disease underwent baseline and 6-month radiofrequency intravascular ultrasound (virtual histology intravascular ultrasound) and computational fluid dynamics modeling for WSS calculation. For each virtual histology intravascular ultrasound segment (n=2249), changes in plaque area, virtual histology intravascular ultrasound-derived plaque composition, and remodeling were compared in low-, intermediate-, and high-WSS categories. Compared with intermediate-WSS segments, low-WSS segments developed progression of plaque area (P=0.027) and necrotic core (P<0.001), whereas high-WSS segments had progression of necrotic core (P<0.001) and dense calcium (P<0.001) and regression of fibrous (P<0.001) and fibrofatty (P<0.001) tissue. Compared with intermediate-WSS segments, low-WSS segments demonstrated greater reduction in vessel (P<0.001) and lumen area (P<0.001), and high-WSS segments demonstrated an increase in vessel (P<0.001) and lumen (P<0.001) area. These changes resulted in a trend toward more constrictive remodeling in low- compared with high-WSS segments (73% versus 30%; P=0.06) and more excessive expansive remodeling in high- compared with low-WSS segments (42% versus 15%; P=0.16). CONCLUSIONS: Compared with intermediate-WSS coronary segments, low-WSS segments develop greater plaque and necrotic core progression and constrictive remodeling, and high-WSS segments develop greater necrotic core and calcium progression, regression of fibrous and fibrofatty tissue, and excessive expansive remodeling, suggestive of transformation to a more vulnerable phenotype. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00576576.

The role of plasma aminothiols in the prediction of coronary microvascular dysfunction and plaque vulnerability.

BACKGROUND: Although oxidative stress is considered a key pathogenic step in mediating vascular dysfunction and atherosclerosis development, their association has not been evaluated in human coronary circulation in vivo. Accordingly, we hypothesized that higher oxidative stress would be associated with abnormal coronary epicardial structure and microvascular function. METHODS: We measured coronary flow velocity reserve (CFVR) and hyperemic microvascular resistance (HMR) as indices of microvascular function, and epicardial plaque volume and necrotic core using intravascular ultrasound (IVUS) in 47 patients undergoing cardiac catheterization. Plasma glutathione, cystine and their ratio served as measures of oxidative stress while high-sensitivity C-reactive protein (hs-CRP) served as a measure of inflammation. RESULTS: Lower glutathione, a measure of increased oxidative stress was associated with impaired microvascular function [CFVR (r=0.39, p=0.01) and HMR (r=-0.43, p=0.004)], greater plaque burden (r=-0.32, p=0.03) and necrotic core (r=-0.39, p=0.008). Similarly, higher cystine/glutathione ratio was associated with impaired microvascular function [CFVR (r=-0.29, p=0.04)] and greater necrotic core (r=0.37, p=0.01). In comparison, higher hs-CRP was associated only with greater necrotic core (r=0.45, p=0.003). After multivariate adjustment for age, gender, hypertension, diabetes, acute coronary syndrome presentation, body mass index, tobacco abuse, statin use and hs-CRP, glutathione remained an independent predictor of CFVR, HMR and necrotic core (p<0.05). CONCLUSIONS: Lower plasma glutathione level a measure of increased oxidative stress, was an independent predictor of impaired coronary microvascular function and plaque necrotic core.

Intravascular imaging tools in the cardiac catheterization laboratory: comprehensive assessment of anatomy and physiology.

Intravascular imaging modalities have an imperative role in contemporary cardiovascular research. Currently, there are several invasive imaging modalities available in the cardiac catheterization laboratory and new technologies are under development. In the current review, we aimed to provide an update on the research applications of contemporary intravascular imaging tools in the cardiac catheterization laboratory. For the purpose of this review, we separately discuss imaging tools for assessment of epicardial disease (fractional flow reserve and hyperemic stenosis resistance), microvascular function (coronary flow reserve, hyperemic microvascular resistance, and index of microcirculatory resistance), endothelial function, atherosclerotic plaque and vascular remodeling (intravascular ultrasound, optical coherence tomography, angioscopy, and near-infrared spectroscopy), and finally the emerging modalities (palpography and wall shear stress profiling).