Aortic Stiffness Is Associated with Coronary Microvascular Dysfunction in Patients with Non-obstructive Coronary Artery Disease.

Objective Associations between aortic stiffness and cardiovascular disease events are mediated in part by pathways that include coronary microvascular dysfunction (CMD) and remodeling. However, the relationship between aortic stiffness and CMD remains unclear. The present study aimed to determine whether aortic stiffness causes CMD as evaluated by the hyperemic microvascular resistance index (hMVRI) in patients with non-obstructive coronary artery disease (CAD). Methods The intracoronary physiological variables in 209 coronary arteries were evaluated in 121 patients with non-obstructive CAD (fractional flow reserve >0.80) or reference vessels. The cardio-ankle vascular index (CAVI) as a measure of aortic stiffness and atherosclerotic risk factors were also measured. Results Univariate analyses showed that hMVRI correlated with age (ß=0.24, p=0.007), eicosapentaenoic acid (EPA; ß=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (ß=-0.22, p=0.014) and CAVI (ß=0.30, p=0.001). A multivariate regression analysis identified CAVI (ß=0.25, p=0.007) and EPA/AA ratio (ß=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI. Conclusion Aortic stiffness may cause CMD in patients with non-obstructive CAD via increased coronary microvascular resistance. Aortic stiffness is associated with CMD which is evaluated as hyperemic microvascular resistance in patients with non-obstructive CAD.

Comprehensive treatment of microvascular angina in overweight women - a randomized controlled pilot trial.

AIMS: Coronary microvascular dysfunction (CMD) carries a poor cardiovascular prognosis and may explain angina in women without obstructive coronary artery disease (CAD). Currently, no evidence-based treatment for CMD exists. We investigated whether reducing cardiovascular risk factors improves symptoms and microvascular function in women with non-endothelial dependent CMD and no obstructive CAD. METHODS: We randomized 62 women aged 40-75, with body mass index (BMI) >25 kg/m2, angina ≥monthly, and coronary flow velocity reserve (CFVR) ≤2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized treatment of hypertension, dyslipidemia and diabetes or to control. Patients were assessed before randomization and after 24 weeks. Primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden by Seattle Angina Questionnaire (SAQ). Secondary outcomes were exercise capacity, body composition, glycemic control, myocardial function, and anxiety and depression symptoms. RESULTS: Fifty-six participants (90%) completed the study. Median (IQR) age was 65.2 (57.1;70.7) years, BMI was 30.1 (28.4;32.7) kg/m2. The intervention resulted in relevant improvement in angina symptoms (9-21-point increase on SAQ-scales (all p<0.01)) but had no effect on CFVR (p = 0.468). Mean (CI) weight loss was 9.6 (7.80;11.48) kg, (p<0.0001). There was a significant mean (CI) decrease in depression symptoms = 1.16 (0.22;2.12), triglycerides = 0.52 (0.25;0.78) mmol/L, total cholesterol = 0.55 (0.12;0.98) mmol/L, and HbA1c in diabetics = 27.1 (1.60;52.6) mmol/mol but no effect on other secondary outcomes. CONCLUSION: A major weight loss and intensified risk factor control resulted in significantly improved angina burden but no improvement of coronary microvascular function among women with microvascular angina.

Effect of Chinese medicine for promoting blood circulation on microvascular angina: A systematic review and meta-analysis.

BACKGROUND: Blood-activating drugs (BADs) are widely used to treat microvascular angina in China. This study aims to summarize relevant evidence from randomized controlled trials (RCTs) to assess the efficacy and safety of BADs in the treatment of microvascular angina. METHODS: We searched for relevant studies before June 2019 from seven databases. Twenty-four studies were included of 1903 patients with microvascular angina. All studies compared the use of traditional Chinese medicine for activating blood circulation (BADs) and Western medicine (WM) with the use of Western medicine alone. RESULTS: In all, 15 trials reported a significant effect of BADs on improving clinical symptoms compared with the control treatment (P < .00001), and 8 trials reported significant effects of BADs on reducing the frequency of angina pectoris attacks compared with Western medicine treatment (P < .00001). The pooled results also demonstrated that BADs provided a significant benefit in reducing the dosage of nitroglycerin required (P = .02), the maximum range of ST-segment depression (P = .003) and the descending degree of the ST-T segment of ECG (P = .0002); prolonging the total time of treadmill exercise (P < .00001) and the time of ST-segment depression of 1 mm (P = .002); enhancing the total effective rate of Traditional Chinese Medicine (TCM) syndromes (P < .00001); improving endothelial function (P < .00001); and reducing the levels of high-sensitivity C-reactive protein (hs-CRP) (P < .00001). BAD treatment showed no statistically significant effect on the levels of TNF-a (P = .8) or IL-6 (P = .13). No severe adverse events were reported. CONCLUSION: This meta-analysis shows that BADs are effective for the treatment of microvascular angina. Although concerns regarding selective bias and low methodological quality were raised, our findings suggest that BADs are beneficial for patients with microvascular angina and should be given priority for future clinical studies.

Role of the central autonomic nervous system intrinsic functional organisation and psychosocial factors in primary microvascular angina and Takotsubo syndrome.

INTRODUCTION AND OBJECTIVE: Dysfunctional central autonomic nervous system network (CAN) at rest may result in aberrant autonomic responses to psychosocial stressors. We hypothesised that patients with primary microvascular angina (MVA) or Takotsubo syndrome (TTS) would exhibit a peculiar functional organisation of the CAN, potentially associated with psychological patterns. METHODS: Patients underwent a psychosocial evaluation: a clinical diagnostic interview, Millon Clinical Multiaxial Inventory III, State-Trait Anxiety Inventory form Y and Short Form 36 Health Survey (SF-36). The strength of intrinsic functional connectivity (FC) between various nodes of the CAN was investigated using cerebral resting state functional MRI (RS-fMRI). RESULTS: We evaluated 50 (46 women) stable patients: 16 patients with MVA, 17 patients with TTS and 17 patients with previous acute myocardial infarction (AMI). Compared with AMI, patients with MVA showed a lower (higher impairment) SF-36 Body-Pain score (p 0.046) and a higher SF-36 Mental-Health score (p 0.039). Patients with TTS showed the strongest FC between two nodes of the CAN (sympathetic midcingulate cortex and parasympathetic primary motor area) (F 6.25, p 0.005) using RS-fMRI. CONCLUSIONS: The study implements an innovative collaborative research among cardiologists, neuroscientists and psychiatrists ('Neuro-psycho-heart Team'). MVA showed a discrepancy between the highest level of self-reported body pain and the best mental health score, which might suggest a mechanism of somatisation. TTS exhibited an increased functional integration between two areas of the CAN involved in interoceptive pain awareness and negative emotional status. We implemented an innovative research collaboration among cardiologists, neuroscientists and psychiatrists. These data are hypothesis generating and suggest potential prospective investigations on pathophysiology and implementation of psychotherapy and stress-reducing techniques as therapeutic strategies. TRIAL REGISTRATION NUMBER: NCT02759341.

Optimal Use of Vasodilators for Diagnosis of Microvascular Angina in the Cardiac Catheterization Laboratory.

BACKGROUND: Among patients with angina and nonobstructive coronary artery disease, those with coronary microvascular dysfunction have a poor outcome. Coronary microvascular dysfunction is usually diagnosed by assessing flow reserve with an endothelium-independent vasodilator like adenosine, but the optimal diagnostic threshold is unclear. Furthermore, the incremental value of testing endothelial function has never been assessed before. We sought to determine what pharmacological thresholds correspond to exercise pathophysiology and myocardial ischemia in patients with coronary microvascular dysfunction. METHODS: Patients with angina and nonobstructive coronary artery disease underwent simultaneous acquisition of coronary pressure and flow during rest, supine bicycle exercise, and pharmacological vasodilatation with adenosine and acetylcholine. Adenosine and acetylcholine coronary flow reserve were calculated as vasodilator/resting coronary blood flow (CFR and AchFR, respectively). Coronary wave intensity analysis was used to quantify the proportion of accelerating wave energy; a normal exercise response was defined as an increase in accelerating wave energy from rest to peak exercise. Ischemia was assessed by quantitative 3-Tesla stress perfusion cardiac magnetic resonance imaging and dichotomously defined by a hyperemic endo-epicardial gradient <1.0. RESULTS: Ninety patients were enrolled (58±10 years, 77% female). Area under the curve using receiver-operating characteristic analysis demonstrated optimal CFR and AchFR thresholds for identifying exercise pathophysiology and ischemia as 2.6 and 1.5, with positive and negative predictive values of 91% and 86%, respectively. Fifty-eight percent had an abnormal CFR (of which 96% also had an abnormal AchFR). Of those with a normal CFR, 53% had an abnormal AchFR, and 47% had a normal AchFR; ischemia rates were 83%, 63%, and 14%, respectively. CONCLUSIONS: The optimal CFR and AchFR diagnostic thresholds are 2.6 and 1.5, with high-positive and negative predictive values, respectively. A normal CFR value should prompt the measurement of AchFR. A stepwise algorithm incorporating both vasodilators can accurately identify an ischemic cause in patients with nonobstructive coronary artery disease.

Impairment of coronary flow velocity reserve and global longitudinal strain in women with cardiac syndrome X and slow coronary flow.

BACKGROUND: Microvascular dysfunction (MVD) is associated with adverse prognosis and may account for abnormal stress tests and angina symptoms in women with cardiac syndrome X (CSX). The aim of our study was to assess MVD by coronary flow velocity reserve (CFVR) and left ventricular (LV) contractile function by LV global longitudinal strain (LVGLS) in CSX patients with respect to presence of slow coronary flow (SCF). It was of additional importance to evaluate clinical status of CSX patients using Seattle Angina Questionnaire. METHODS AND RESULTS: Study population included 70 women with CSX (mean age 61 ± 7 years) and 34 age-matched controls. CSX group was stratified into two subgroups depending on SCF presence: CSX-Thrombolysis In Myocardial Infarction (TIMI) 3- normal flow subgroup (n = 38) and CSX-TIMI 2- SCF subgroup (n = 32) as defined by coronary angiography. LVGLS measurements and CFVR of left anterior descending (LAD) and posterior descending (PD) artery were performed. CFVR-LAD and PD were markedly impaired in CSX group compared to controls (2.34 ± 0.25 vs 3.05 ± 0.21, p < 0.001; 2.32 ± 0.24 vs 3.01 ± 0.13, p < 0.001), and furthermore decreased in CSX-TIMI 2 patients. Resting, peak, and ΔLVGLS were all significantly impaired in CSX group compared to controls (for all p < 0.001), and furthermore reduced in CSX-TIMI 2 subgroup. Strongest correlation was found between peak LVGLS and CFVR LAD (r = -0.784, p < 0.001) and PD (r = -0.772, p < 0.001). CSX-TIMI 2 subgroup had more frequent angina symptoms and more impaired quality of life. CONCLUSIONS: MVD in CSX patients is demonstrated by reduction in CFVR and LVGLS values. SCF implies more profound impairment of microvascular and LV systolic function along with worse clinical presentation.

Marked Impairment of Endothelium-Dependent Digital Vasodilatations in Patients With Microvascular Angina: Evidence for Systemic Small Artery Disease.

OBJECTIVE: It remains to be elucidated whether and how endothelial functions are impaired in peripheral circulation of patients with coronary functional disorders, such as vasospastic angina (VSA) and microvascular angina (MVA). We simultaneously examined endothelial functions of peripheral conduit and resistance arteries in patients with coronary functional disorders, with a special reference to NO and endothelium-dependent hyperpolarization factors. Approach and Results: Based on the results of invasive coronary acetylcholine testing and coronary physiological measurements, we divided 43 patients into 3 groups; VSA, MVA, and VSA+MVA. Endothelium-dependent vasodilatations of the brachial artery and fingertip arterioles to intra-arterial infusion of bradykinin were simultaneously evaluated by ultrasonography and peripheral arterial tonometry, respectively. To assess NO and endothelium-dependent hyperpolarization factors, measurements were repeated after oral aspirin and intra-arterial infusion of NG-monomethyl-L-arginine. Additionally, endothelium-independent vasodilatations to sublingual nitroglycerin and plasma levels of biomarkers for endothelial functions were measured. Surprisingly, digital vasodilatations to bradykinin were almost absent in patients with MVA alone and those with VSA+MVA compared with those with VSA alone. Mechanistically, both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations were markedly impaired in patients with MVA alone. In contrast, endothelium-independent vasodilatations to nitroglycerin were comparable among the 3 groups. Plasma levels of soluble VCAM (vascular cell adhesion molecule)-1 were significantly higher in patients with MVA alone compared with those with VSA alone. CONCLUSIONS: These results provide the first evidence that both NO- and endothelium-dependent hyperpolarization-mediated digital vasodilatations are markedly impaired in MVA patients, suggesting that MVA is a cardiac manifestation of the systemic small artery disease.

Whole blood viscosity in microvascular angina and coronary artery disease: Significance and utility.

INTRODUCTION AND OBJECTIVES: Whole blood viscosity (WBV) is the intrinsic resistance of blood flow in vessels, and when elevated induces endothelial shear stress and endothelial inflammation and can accelerate the atherosclerotic process. This study aims to compare WBV levels in patients with microvascular angina (MVA), patients with coronary artery disease (CAD), and normal controls, and to identify the relationship between WBV and high-sensitivity C-reactive protein as a marker of inflammation in MVA and CAD. METHODS: A total of 573 patients were studied. The MVA group consisted of 189 subjects, the CAD group consisted of 203 subjects, and the control group consisted of 181 age- and gender-matched individuals. WBV was calculated from hematocrit and plasma protein concentration at a low shear rate (0.5 s-1) and high shear rate (208 s-1) by a validated equation. RESULTS: Patients with CAD and MVA had significantly higher WBV at both low and high shear rates compared to the control group. Correlation analysis revealed a significant relationship between high-sensitivity C-reactive protein and WBV at low (r=0.556; p<0.001) and high shear rates (r=0.562) in the CAD group and at low (r=0.475) and high shear rates (r=0.493) in the MVA group. CONCLUSIONS: Overall, this study demonstrated a significant and independent association between blood viscosity and the existence of endothelial inflammation and the atherosclerotic process.

Coronary microvascular dysfunction.

Patients with coronary microvascular dysfunction (CMVD) represent a widespread population and despite the good prognosis, many of them have a poor quality of life with strong limitations in their daily activities because of the angina symptoms. This article summarizes the most frequent clinical presentation pictures like stable and unstable microvascular angina. Main risk factors are discussed, followed by the latest updates on the subject about different pathogenic hypotheses, diagnosis and treatment. Not very well understood microvascular alterations, like slow flow phenomenon and no reflow are discussed and both prognosis and the impact of the disease in the quality of life are analyzed.

Utility of discovery approach using proteomics to create a biomarker profile for coronary microvascular dysfunction.

INTRODUCTION: Coronary microvascular dysfunction (CMD) is a complex disease, difficult to diagnose and often requires advanced imaging. We used mass spectrometry (MS) using discovery approach to search for serum proteins as potential biomarkers in these patients. METHODS: We used serum samples from 10 patients with CMD and 10 with normal coronary flow reserve (CFR) admitted to an observation unit where acute myocardial infarction was excluded. We identified CMD using 82Rb positron emission tomography/computed tomography as CFR <2 in response to regadenoson, in the absence of coronary calcification or regional perfusion defects. We used MS to identify potential protein biomarkers that were differentially expressed in cases and controls. RESULTS: Baseline characteristics were not different between cases and controls, except for beta-blocker use and which was higher in cases, and mean (SD) CFR which was lower in cases [1.19 (0.23) and 2.78 (0.78) in cases and controls respectively; p < 0.01]. We identified 5345 peptides corresponding to 209 proteins, and identified 197 proteins by peptides with suitable properties to infer relative quantitation values. While the calculated values for some proteins (e.g. vascular cell adhesion molecule-1, apolipoprotein C and Von Willebrand Factor) indicate fold-differences between groups, these are most likely a result of high values in only 1-2 patients and are not statistically significant. CONCLUSION: Mass spectrometry using discovery approach may not be an adequate method for quantitative assessment of serum proteins in CMD patients. Future MS studies should evaluate other approaches including tissue samples or serial measurements.

Rationale and design of the British Heart Foundation (BHF) Coronary Microvascular Function and CT Coronary Angiogram (CorCTCA) study.

Microvascular and/or vasospastic anginas are relevant causes of ischemia with no obstructive coronary artery disease (INOCA) in patients after computed tomography coronary angiography (CTCA). OBJECTIVES: Our research has 2 objectives. The first is to undertake a diagnostic study, and the second is to undertake a nested, clinical trial of stratified medicine. DESIGN: A prospective, multicenter, randomized, blinded, sham-controlled trial of stratified medicine (NCT03477890) will be performed. All-comers referred for clinically indicated CTCA for investigation of suspected coronary artery disease (CAD) will be screened in 3 regional centers. Following informed consent, eligible patients with angina symptoms are enrolled before CTCA and remain eligible if CTCA excludes obstructive CAD. Diagnostic study: Invasive coronary angiography involving an interventional diagnostic procedure (IDP) to assess for disease endotypes: (1) angina due to obstructive CAD (fractional flow reserve ≤0.80); (2) microvascular angina (coronary flow reserve <2.0 and/or index of microvascular resistance >25); (3) microvascular angina due to small vessel spasm (acetylcholine); (4) vasospastic angina due to epicardial coronary spasm (acetylcholine); and (5) noncoronary etiology (normal coronary function). The IDP involves direct invasive measurements using a diagnostic coronary guidewire followed by provocation testing with intracoronary acetylcholine. The primary outcome of the diagnostic study is the reclassification of the initial CTCA diagnosis based on the IDP. Stratified medicine trial: Participants are immediately randomized 1:1 in the catheter laboratory to therapy stratified by endotype (intervention group) or not (control group). The primary outcome of the trial is the mean within-subject change in Seattle Angina Questionnaire score at 6 months. Secondary outcomes include safety, feasibility, diagnostic utility (impact on diagnosis and certainty), and clinical utility (impact on treatment and investigations). Health status assessments include quality of life, illness perception, anxiety-depression score, treatment satisfaction, and physical activity. Participants who are not randomized will enter a follow-up registry. Health and economic outcomes in the longer term will be assessed using electronic patient record linkage. VALUE: CorCTCA will prospectively characterize the prevalence of disease endotypes in INOCA and determine the clinical value of stratified medicine in this population.

Effects of a Cardiac Rehabilitation Program Versus Usual Care on Cardiopulmonary Function in Patients With Cardiac Syndrome X.

PURPOSE: Because of uncertainty in the pathophysiological process, the treatment of cardiac syndrome X (CSX) is still under study. Addressing the effects of cardiac rehabilitation (CR) can help promote the prescription of this modality as an adjuvant therapy for these patients. METHODS: This study was performed on 30 patients with effort-induced angina pectoris using a positive exercise test and/or myocardial perfusion scan in the absence of obvious stenosis or a stenosis of <50% on coronary angiography. The patients were divided into the CR and usual care (UC) groups and underwent cardiopulmonary exercise testing with gas exchange analysis before and after the study. The Duke Treadmill Score was used to compare prognosis and survival estimates of patients. RESULTS: An increase in peak oxygen uptake ((Equation is included in full-text article.)O2) was significantly higher in the CR group than in the control group (P = .017). Resting (Equation is included in full-text article.)O2 was also increased in the CR group, but its difference with the UC group was not statistically significant. Resting O2 pulse was increased in the CR group, which significantly differed between groups (P = .041). Exercise test duration and the Duke Treadmill Score significantly increased in the CR group as compared with the UC group (P = .003 and P = .002, respectively). Also, recovery heart rate in the first minute was significantly improved in CR group. CONCLUSION: Adding a 4-wk course of CR to UC for patients with CSX not only increased the Duke Treadmill Score and exercise test duration but also improved the resting O2 pulse, peak (Equation is included in full-text article.)O2, and first-minute recovery heart rate.

Ischemia and No Obstructive Coronary Artery Disease: Prevalence and Correlates of Coronary Vasomotion Disorders.

BACKGROUND: Determine the prevalence and correlates of microvascular and vasospastic angina in patients with symptoms and signs of ischemia but no obstructive coronary artery disease (INOCA). METHODS: Three hundred ninety-one patients with angina were enrolled at 2 regional centers over 12 months from November 2016 (NCT03193294). INOCA subjects (n=185; 47%) had more limiting dyspnea (New York Heart Association classification III/IV 54% versus 37%; odds ratio [OR], 2.0 [1.3-3.0]; P=0.001) and were more likely to be female (68% INOCA versus 38% in coronary artery disease; OR, 1.9 [1.5 to 2.5]; P<0.001) but with lower cardiovascular risk scores (ASSIGN score median 20% versus 24%; P=0.003). INOCA subjects had similar burden of angina (Seattle Angina Questionnaire) but reduced quality of life compared with coronary artery disease; subjects (EQ5D-5 L index 0.60 versus 0.65 units; P=0.041). RESULTS: An interventional diagnostic procedure with reference invasive tests including coronary flow reserve, microvascular resistance, and vasomotor responses to intracoronary acetylcholine (vasospasm provocation) was performed in 151 INOCA subjects. Overall, 78 (52%) had isolated microvascular angina, 25 (17%) had isolated vasospastic angina, 31 (20%) had both, and 17 (11%) had noncardiac chest pain. Regression analysis showed inducible ischemia on treadmill testing (OR, 7.5 [95% CI, 1.7-33.0]; P=0.008) and typical angina (OR, 2.7 [1.1-6.6]; P=0.032) were independently associated with microvascular angina. Female sex tended to associate with a diagnosis of microvascular angina although this was not significant (OR, 2.7 [0.9-7.9]; P=0.063). Vasospastic angina was associated with smoking (OR, 9.5 [2.8-32.7]; P<0.001) and age (OR, 1.1 per year, [1.0-1.2]; P=0.032]. CONCLUSIONS: Over three quarters of patients with INOCA have identifiable disorders of coronary vasomotion including microvascular and vasospastic angina. These patients have comparable angina burden but reduced quality of life compared to patients with obstructive coronary artery disease. Microvascular angina and vasospastic angina are distinct disorders that may coexist but differ in associated clinical characteristics, symptoms, and angina severity. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193294.

Assessment of the relationship between coronary flow rates and myocardial perfusion abnormality in patients with nonobstructive coronary artery disease: an observational study in cardiac syndrome X and coronary slow flow.

OBJECTIVES: In this study, we evaluated and compared the level of myocardial ischaemia caused by cardiac syndrome X (CSX) and coronary slow flow (CSF) with single photon emission computed tomography myocardial perfusion imaging (SPECT-MPI), and determined if changes in the level of myocardial ischaemia exist in CSF and CSX cases according to thrombolysis in myocardial infarction frame count (TFC). MATERIALS AND METHODS: The study population consisted of 66 patients with CSF and 78 angiographically normal patients (36 of them with CSX and 42 of them healthy controls). The coronary flow rates of all patients were documented using TFC. Subsequently, all patients were evaluated with SPECT-MPI and categorized into the following groups according to their results: patients with CSF, patients with CSX, and patients with normal coronary arteries. Finally, we investigated whether a relationship existed between the SPECT-MPI and TFC results from these three groups. RESULTS: All ischaemia scores for MPI were significantly higher in the CSF group than in the CSX and control groups (P < 0.05). TFC was significantly associated with the severity of ischaemia in the CSF patients. There was a significant positive correlation between the summon difference score (SDS) and mean TFC value (P < 0.05) as well as between the SDS and each individual coronary TFC value in the CSF patients (P < 0.05). The number of vessels involved in CSF was positively correlated with the SDS. CONCLUSION: CSF is associated with more severe myocardial ischaemia than CSX. The level of myocardial ischaemia on SPECT-MPI was correlated with the TFC and the number of affected coronary vessels in patients with CSF. These results suggest that CSF is a more serious clinical entity than CSX, and that the clinical severity of CSF appears to increase as the coronary flow rate decreases.

'Acute micro-coronary syndrome': detailed coronary physiology in a patient with Takotsubo cardiomyopathy.

Takotsubo cardiomyopathy (TC), otherwise known as stress cardiomyopathy, is characterised by acute, transient left ventricular systolic dysfunction with apical ballooning in the absence of obstructive epicardial coronary stenosis. The presentation of TC mimics that of acute myocardial infarction. More recently there has been a shift towards thinking of TC as a 'microvascular acute coronary syndrome'. Our case is of an 82-year-old woman who presented with TC mimicking acute anterior ST elevation myocardial infarction in the context of sepsis. Slow flow noted in the left anterior descending artery prompted us to perform coronary physiology. Her fractional flow reserve was 0.91, with an index of myocardial resistance of 117 and a coronary flow reserve of 1.6. In combination these results are indicative of microvascular coronary dysfunction in the absence of significant epicardial stenosis.

Retinal microvascular changes in microvascular angina: Findings from the Australian Heart Eye Study.

OBJECTIVE: Microvascular changes in microvascular angina are poorly understood due to difficulties in imaging the coronary microcirculation in vivo. The retinal microvasculature may reflect changes in coronary microcirculation. We assessed microvascular changes in the retina in patients with microvascular angina and compared them with patients with angiographically proven coronary artery disease. METHODS: We performed retinal photography and coronary angiography on 915 patients. Retinal vessel calibers were measured using a validated computer-assisted method; coronary artery disease was graded from coronary angiograms. Microvascular angina was defined as angina with <25% stenosis in all coronary epicardial arteries. RESULTS: A total of 139 patients (15.2%) had microvascular angina, while 776 (84.8%) had coronary artery disease. Participants with microvascular angina and coronary artery disease had similar retinal arteriolar and venular calibers. After adjustment for age, ethnicity, mean arterial pressure, diabetes, current smoking, body mass index, and fellow vessel caliber, women with smaller venules were threefold more likely to have microvascular angina than women with larger venules (multivariable-adjusted odds ratio 3.54, 95% confidence interval 1.35 to 9.24, P < 0.01). This difference was not observed in men. CONCLUSIONS: Microvascular angina in women was associated with microvascular changes distinct from those in coronary artery disease.

Index of microvascular resistance to assess the effect of rosuvastatin on microvascular function in women with chest pain and no obstructive coronary artery disease: A double-blind randomized study.

INTRODUCTION: Many women undergoing coronary angiography for chest pain have no or only minimal coronary artery disease (CAD). However, despite the lack of obstructive CAD, they still have an increased risk of major adverse cardiovascular events. Pleiotropic effects of statins may influence microvascular function, but if statins improve microvascular function in unselected chest pain patients is not well studied. This study assessed microvascular function by using the thermodilution-derived test "the index of microvascular resistance" (IMR) with the aim of determining the (i) IMR level in women with chest pain and non-obstructive CAD and if (ii) IMR is modified by high-dose statin treatment in these patients. Additional objectives were to identify the influence of statins on the health status as assessed with generic health questionnaires and on biomarkers of endothelial activation. MATERIALS AND METHODS: The study was a randomized, double-blind, single-center trial comparing 6 months of rosuvastatin treatment with placebo. In total, 66 women without obstructive CAD were included. Mean age was 52.7 years and 55.5 years in the placebo and rosuvastatin group, respectively. Microvascular function was assessed using the IMR, health status was assessed using the SF-36 and EQ-5D questionnaires, and biochemical values were assessed at baseline and 6 months later. RESULTS AND CONCLUSIONS: In the placebo group IMR was 14.6 (SD 5.7) at baseline and 14.4 (SD 6.5) at follow-up. In the rosuvastatin group IMR was 16.5 (SD 7.5) at baseline and 14.2 (SD 5.8) at follow-up. IMR did not differ significantly between the two study groups at follow-up controlled for preintervention values. C-reactive protein (CRP) was comparable between the groups at baseline, while at follow-up CRP was significantly lower in the rosuvastatin group compared to placebo [0.6 (±0.5) mg/L vs. 2.6 (±3.0) mg/L; p = 0.002]. Whereas rosuvastatin treatment for 6 months attenuated CRP levels, it did not improve microvascular function as assessed by IMR (Clinical Trials.gov NCT01582165, EUDRACT 2011-002630-39.3tcAZ).

Physical training improves myocardial perfusion but not left ventricular function response to exercise in patients with microvascular angina.

BACKGROUND: Patients with primary microvascular angina (PMA) commonly exhibit abnormal left ventricular function (LVF) during exercise, potentially owing to myocardial ischemia. Herein, we investigated in PMA patients the effect of the reduction of myocardial perfusion disorders, by using aerobic physical training, upon LVF response to exercise. METHODS: Overall, 15 patients (mean age, 53.7±8.9 years) with PMA and 15 healthy controls (mean age, 51.0±9.4 years) were studied. All subjects were subjected to baseline resting and exercise ventriculography, myocardial perfusion scintigraphy (MPS), and cardiopulmonary testing. PMA group members then participated in a 4-month physical training program and were reevaluated via the same methods applied at baseline. RESULTS: Baseline left ventricular ejection fraction (LVEF) determinations by ventriculography were similar for both groups (PMA, 67.7±10.2%; controls, 66.5±5.4%; P=0.67). However, a significant rise in LVEF seen in control subjects during exercise (75.3±6.2%; P=0.0001) did not materialize during peak exercise in patients with PMA (67.7±10.2%; P=0.47). Of the 12 patients in the PMA group who completed the training program, 10 showed a significant reduction in reversible perfusion defects during MPS. Nevertheless, LVEF at rest (63.5±8.7%) and at peak exercise (67.3±15.9%) did not differ significantly (P=0.30) in this subset. CONCLUSIONS: In patients with PMA, reduced left ventricular inotropic reserve observed during exercise did not normalize after improving myocardial perfusion through aerobic physical training.