Coronary microvascular dysfunction assessment: A comparative analysis of procedural aspects.

BACKGROUND: Full adoption of coronary microvascular dysfunction (CMD) assessment faces challenges due to its invasive nature and concerns about prolonged procedure time and increased contrast and/or radiation exposure. We compared procedural aspects of CMD invasive assessment to diagnostic left heart catheterization (DLHC) in patients with chest pain who were not found to have obstructive coronary artery disease. METHODS: A total of 227 patients in the Coronary Microvascular Disease Registry were compared to 1592 patients who underwent DLHC from August 2021 to November 2023. The two cohorts were compared using propensity-score matching; primary outcomes were fluoroscopy time and total contrast use. RESULTS: The participants' mean age was 64.1 ± 12.6 years. CMD-assessed patients were more likely to be female (66.5% vs. 45.2%, p < 0.001) and have hypertension (80.2% vs. 44.5%, p < 0.001), history of stroke (11.9% vs. 6.3%, p = 0.002), and history of myocardial infarction (20.3% vs. 7.7%, p < 0.001). CMD assessment was safe, without any reported adverse outcomes. A propensity-matched analysis showed that patients who underwent CMD assessment had slightly higher median contrast exposure (50 vs. 40 mL, p < 0.001), and slightly longer fluoroscopy time (6.9 vs. 4.7 min, p < 0.001). However, there was no difference in radiation dose (209.3 vs. 219 mGy, p = 0.58) and overall procedure time (31 vs. 29 min, p = 0.37). CONCLUSION: Compared to DLHC, CMD assessment is safe and requires only slightly additional contrast use (10 mL) and slightly longer fluoroscopy time (2 min) without clinical implications. These findings emphasize the favorable safety and feasibility of invasive CMD assessment.

Initial single-center experience of a standardized protocol for invasive assessment of ischemia and non-obstructive coronary artery disease.

INTRODUCTION: Coronary vasomotion disorders (CVDs), including microvascular angina (MVA) and vasospastic angina (VSA), account for significant morbidity among patients with non-obstructive coronary artery disease (NOCAD). However, protocols for CVD assessment in clinical practice are seldom standardized and may be difficult to implement. PURPOSE: To assess the safety and feasibility of a comprehensive coronary function test (CFT) protocol for assessment of CVD and the prevalence of different phenotypes of CVD in patients with angina and NOCAD (ANOCA). METHODS: Patients with persistent angina referred for invasive coronary angiogram and found to have NOCAD were prospectively recruited and underwent a CFT. Functional parameters (fractional flow reserve, coronary flow reserve and index of myocardial resistance) and coronary vasoreactivity were assessed in all patients. RESULTS: Of the 20 patients included, the mean age was 63±13 years and 50% were females. Most patients had persistent typical angina and evidence of ischemia in noninvasive tests (75%). The CFT was successfully performed in all subjects without serious complications. Isolated MVA was found in 25%, isolated VSA in 40%, both MVA and VSA in 10% and noncardiac chest pain in 25% of patients. Antianginal therapy was modified after the results of CFT in 70% of patients. CONCLUSION: A coronary function test was feasible and safe in a cohort of patients with ANOCA. CVD were prevalent in this selected group of patients, and some presented mixed CVD phenotypes. CFT may provide a definitive diagnosis in patients with persistent angina and prompt the stratification of pharmacological therapy.

Transthoracic Doppler echocardiography compared with positron emission tomography for assessment of coronary microvascular dysfunction: The iPOWER study.

BACKGROUND: Coronary microvascular function can be assessed by transthoracic Doppler echocardiography as a coronary flow velocity reserve (TTDE CFVR) and by positron emission tomography as a myocardial blood flow reserve (PET MBFR). PET MBFR is regarded the noninvasive reference standard for measuring coronary microvascular function but has limited availability. We compared TTDE CFVR with PET MBFR in women with angina pectoris and no obstructive coronary artery disease and assessed repeatability of TTDE CFVR. METHODS: From a cohort of women with angina and no obstructive coronary artery stenosis at invasive coronary angiography, TTDE CFVR by dipyridamole induced stress and MBFR by rubidium-82 PET with adenosine was successfully measured in 107 subjects. Repeatability of TTDE CFVR was assessed in 10 symptomatic women and in 10 healthy individuals. RESULTS: MBFR was systematically higher than CFVR. Median MBFR (interquartile range, IQR) was 2.68 (2.29-3.10) and CFVR (IQR) was 2.31 (1.89-2.72). Pearson's correlation coefficient was 0.36 (p<0.01). Limits of agreement (2·standard deviation) assessed by the Bland-Altman (confidence interval, CI) method was 1.49 (1.29;1.69) and unaffected by time-interval between examinations. Results were similar when adjusting for rate pressure product or focusing on perfusion of the left anterior descending artery region. Limits of agreement (CI) for repeated CFVR in 10 healthy individuals and in 10 women with angina was 0.44 (0.21;0.68) and 0.48 (0.22; 0.74), respectively. CONCLUSION: CFVR had a good repeatability, but the agreement between CFVR and MBFR was modest. Divergence could be due to methodology differences; TTDE estimates flow velocities whereas PET estimates myocardial blood flow.

Does Inflammation Have a Role in the Pathogenesis of Cardiac Syndrome X? A Genetic-Based Clinical Study With Assessment of Multiple Cytokine Levels.

We compared Turkish patients with cardiac syndrome X (CSX) and controls with respect to serum pro- and anti-inflammatory cytokine levels, as well as the single-nucleotide polymorphisms located in the promoter regions of their related genes. This study included 111 consecutive patients angiographically diagnosed with CSX and 111 healthy controls with similar demographic characteristics. Serum interleukin (IL) 6, tumor necrosis factor α (TNF-α), and IL-10 levels were measured, and the genotypes of the patients and controls were determined using standard methods. Serum IL-6 and IL-10 levels were significantly higher in the CSX group than in the control group (P < .01, respectively). Serum TNF-α level was lower in the CSX group than in the control group (P < .001). On the other hand, participants with CSX and healthy controls were not significantly different with respect to the genotype distributions of IL-6, TNF-α, and IL-10 genes. As a result of our study, both pro-inflammatory and anti-inflammatory cytokines may play a role in the pathogenesis of CSX. In contrast, the studied gene polymorphisms did not influence CSX pathogenesis.

Assessment of the relationship between red cell distribution width and cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) is characterised by angina-like chest pain, a positive stress test, and normal coronary arteries. Increased red cell distribution width (RDW) level may be indicative of an underlying inflammatory state. AIM: To investigate RDW level in patients with CSX and compare patients having coronary artery disease (CAD) and normal subjects. METHODS: 245 subjects (79 patients with CSX, 81 patients with CAD, and 85 controls) were enrolled in the study. The CSX group consisted of patients with anginal chest pain, ischaemia on noninvasive stress test and a normal coronary angiogram.CAD was defined as ≥ 50% stenosis in at least one coronary artery. The control group was selected from the patients with anginal symptoms but a normal stress test and a normal coronary angiogram. RDW measurements among the three groups were compared. RESULTS: Baseline clinical and biochemical characteristics were not different among the three groups. There were no statistically significant differences in RDW levels between the CSX and CAD groups (p = 0.17). RDW measurements in both the CSX and CAD groups were found to be significantly higher than the control group (p < 0.01). CONCLUSIONS: We discovered that patients with CSX and CAD have significantly higher RDW measurements compared to controls. The relationship between CSX and higher RDW level suggests that endothelial dysfunction may also contribute to the etiopathogenesis of the CSX phenomenon as it does with CAD.

Women, cardiac syndrome X, and microvascular heart disease.

New data suggest that persistent chest pain, despite normal coronary angiography, is less benign than previously thought. It has long been recognized that cardiac syndrome X (CSX) is associated with significant suffering, disability, and health care costs, but the biggest shift in thinking comes in terms of long-term risk. It is now recognized that the prognosis is not benign and that a significant proportion of patients are at increased cardiovascular disease risk. Of major debate is the question of whether the mechanisms that explain this chest pain are cardiac vs noncardiac. The most current definition of CSX is the triad of angina, ischemia, and normal coronary arteries, which is associated with an increased cardiovascular risk. This paper provides a review of CSX, epidemiology of the problem, proposed explanatory mechanisms, and important next steps in research. Central to this review is the proposition that new insights into CSX will be fostered by both clinical and scientific collaboration between cardiovascular and pain scientists.

Microvascular angina: assessment of coronary blood flow, flow reserve, and metabolism.

Microvascular angina (MVA) is an often overlooked cause of significant chest pain. Decreased myocardial perfusion secondary to dysregulated blood flow in the microvasculature can occur in the presence or absence of obstructive epicardial coronary artery disease. The corresponding myocardial ischemia and angina is now a well-established diagnosis, made by detection of decreased coronary flow reserve (CFR). Although low CFR and MVA are associated with poor prognosis, there is initial evidence for reversibility of this abnormal vascular regulation with aggressive medical therapy and control of associated risk factors. Current assessment of MVA is carried out predominantly during cardiac catheterization; however, noninvasive techniques to assess CFR are being developed, including PET, MRI, and CT modalities. Quantitative tracer techniques or imaging of metabolic disturbances reflecting ischemia will likely enhance diagnostic approaches for such patients as well as allow more frequent monitoring of response to therapy.

Reproducibility and repeatability of peripheral microvascular assessment using iontophoresis in conjunction with laser Doppler imaging.

Interrogation of peripheral vascular function is increasingly recognized as a noninvasive surrogate marker for coronary vascular function and carries with it important prognostic information regarding future cardiovascular risk. Laser Doppler imaging (LDI) is a completely noninvasive method for looking at peripheral microvascular function. We sought to look at reproducibility and repeatability of LDI-derived assessment of peripheral microvascular function between arms and 8 weeks apart. We used LDI in conjunction with iontophoretic application of ACh and SNP to look at endothelium-dependent and -independent microvascular function, respectively, in a mixture of women with cardiac syndrome X and healthy volunteers. We looked at variation between arms (n = 40) and variation at 8 weeks apart (n = 22). When measurements were corrected for skin resistance, there was nonsignificant variation between arms for ACh (2.7%) and SNP (3.8%) and nonsignificant temporal variation for ACh (3.5%) and SNP (4.7%). Construction of Bland-Altman plots reinforce that measurements have good repeatability. Elimination of the baseline perfusion response had deleterious effects on repeatability. LDI can be used to assess peripheral vascular response with good repeatability as long as measurements are corrected for skin resistance, which affects drug delivery. This has important implications for the future use of LDI.

Assessment of arterial distensibility in patients with cardiac syndrome X.

This study aims to investigate arterial distensibility by using carotid-femoral (aortic) pulse wave velocity measurements in patients with cardiac syndrome X. The authors studied 10 patients with cardiac syndrome X (mean age 49.4 +/-7.5, 39 to 67 years old, 3 men) and 10 healthy subjects (mean age 50.0 +/-10.5, 38 to 70 years old, 3 men). Carotid-femoral pulse wave velocity measured by a Complior Colson device was calculated for each patient. The carotid-femoral pulse wave velocity was increased in patients with cardiac syndrome X as compared with age-matched control subjects (10.25 +/-1.28 vs 8.95 +/-0.89 m/s, p = 0.01). In contrast, there were no significant differences in the age, weight, height, body mass index, waist/hip ratio, systolic blood pressure, diastolic blood pressure, mean blood pressure, pulse pressure, and heart rate (p=0.76,p=0.17,p=0.36,p=0.08, p=0.21,p=0.14,p=0.89,p=0.30,p=0.10, p = 0.36, respectively). No significant correlation was found between pulse wave velocity and age, sex, height, weight, heart rate, systolic blood pressure, diastolic blood pressure, mean blood pressure, and pulse pressure in the studied groups (p>0.05). The arterial distensibility was decreased in patients with cardiac syndrome X. The deterioration in these patients showed that this disease might be a more generalized disturbance of the vasculature. Measurements of carotid-femoral pulse wave velocity may provide a simple and noninvasive technique to identify patients at increased risk of vascular disease.

Assessment of quality of life in patients with chest pain and normal coronary arteriogram (syndrome X) using a specific questionnaire.

BACKGROUND: Prognosis in patients with syndrome X (chest pain and normal coronary arteriograms) is good; however, persistent chest pain and functional disability are common in these patients. Accurate assessment of quality of life may be useful for patient management. AIM: The quality of life status in patients with syndrome X was assessed using a specific questionnaire. This questionnaire was developed and validated for the assessment of quality of life in patients with typical chest pain despite normal coronary arteriograms. METHODS: Ninety consecutive patients were invited to complete both the questionnaire (on two occasions within 2 weeks) and a standardized angina dairy. Fully completed questionnaires were received from 66 (73%) patients (mean age 58 +/- 8 years, 55 women). RESULTS: Answers were scored according to a grading system where higher scores indicate worse quality of life. We observed that total scores increased with severity of angina (Canadian Class I, 38 +/- 16, II: 93 +/- 29, III-IV, 119 +/- 23; p < 0.001) and correlated with both the number and the severity of chest pain episodes (r = 0.50-0.66: p < 0.001). In patients who remained clinically stable (n = 37) during the 2-week assessment, test-retest analysis showed no score differences (87 +/- 30 vs. 81 +/- 30; p = 0.1), while total score increased in patients (n = 24) whose symptoms worsened (108 +/- 31 vs. 116 +/- 31; p < 0.02) and was reduced in those (n = 5) whose symptoms improved (55 +/- 37 vs. 39 +/- 28; p < 0.04). CONCLUSION: Our study shows that quality of life is significantly impaired in patients with syndrome X and that the specific questionnaire used for assessment is a reliable and sensitive tool for the evaluation of quality of life in patients with chest pain and normal coronary arteriograms.

Myocardial perfusion reserve: assessment with multisection, quantitative, first-pass MR imaging.

PURPOSE: To demonstrate the feasibility of determining myocardial blood flow changes and the myocardial perfusion reserve with magnetic resonance (MR) first-pass imaging, to validate the MR results by means of comparison with radiolabeled microsphere flow measurements in an animal model, and to compare the coronary flow reserve with the perfusion reserve at MR imaging in patients with hemodynamically nonsignificant coronary lesions and angina. MATERIALS AND METHODS: Arrhythmia-insensitive, first-pass, multisection, T1-weighted MR imaging with contrast agent enhancement was performed in eight pigs with acute ischemia and in eight adult patients (six women, two men). In the pigs, microsphere flow measurements were obtained in parallel with the MR measurements. In the patients, the coronary flow reserve was measured with an intracoronary Doppler flow ultrasound probe for comparison with the MR perfusion reserve. RESULTS: In the animal studies, there was linear correlation between MR perfusion indexes and the microsphere flow measurements (r = .88, P < .01). In the patients, the regional perfusion reserve matched the coronary flow reserve (linear regression with a slope of 1.02 +/- 0.09, r = .80). CONCLUSION: The myocardial perfusion reserve can be quantified with first-pass MR imaging. In patients with microvascular dysfunction, the myocardial perfusion reserve matches the reduced coronary flow reserve.