Myocardial perfusion by CMR coronary sinus flow shows sex differences and lowered perfusion at stress in patients with suspected microvascular angina.

BACKGROUND: Patients with chest pain may have normal coronary arteries and suffer from microvascular angina (MVA). The aim of this study was to determine if patients with suspected MVA have lower global myocardial perfusion (global MP) during adenosine stress compared with healthy controls and coronary artery disease (CAD) patients and to determine if there are sex differences in global MP. METHODS: Twenty-three patients with suspected MVA (66 ± 11 years), 19 CAD patients (69 ± 5 years) with stress-induced ischaemia and 24 healthy controls (61 ± 10 years) underwent cardiac magnetic resonance (CMR) including coronary sinus flow measurements and first-pass perfusion at rest and during adenosine stress. Global MP was quantified as coronary sinus flow normalized to left ventricular mass. RESULTS: Global perfusion was lower during stress in patients with suspected MVA (2.9 ± 1.0 ml/min/g) compared with healthy volunteers (3.7 ± 1.1 ml/min/g, p = 0.018), but higher compared with CAD patients (2.0 ± 0.9 ml/min/g, p = 0.019). Female controls had higher global MP than male controls both at rest (1.0 ± 0.3 vs. 0.7 ± 0.2 ml/min/g, p = 0.003) and during stress (4.4 ± 1.0 vs. 3.1 ± 0.6 ml/min/g, p = 0.001). Furthermore, females with suspected MVA showed higher global MP than males with suspected MVA (3.3 ± 1.0 vs. 2.4 ± 0.7, p = 0.04). CONCLUSIONS: Patients with suspected MVA have lower global MP at stress than healthy volunteers but higher than patients with CAD. Furthermore, there seems to be a sex difference in global MP at stress both in healthy volunteers and in patients with suspected MVA, with higher global MP in females, which implies a need for sex-specific normal limits when assessing quantitative MP.

Long-Term Prognosis of Patients With Coronary Microvascular Disease Using Stress Perfusion Cardiac Magnetic Resonance.

OBJECTIVES: This study investigated the prognosis of coronary microvascular disease (CMD) as determined by stress perfusion cardiac magnetic resonance (CMR) in patients with ischemic symptoms but without significant coronary artery disease (CAD). BACKGROUND: Patients with CMD have poorer prognosis with various cardiac diseases. The myocardial perfusion reserve index (MPRI) derived from noninvasive stress perfusion CMR has been established to diagnose microvascular angina with a threshold MPRI <1.4. The prognosis of CMD as determined by MPRI is unknown. METHODS: Chest pain patients without epicardial CAD or myocardial disease from January 2009 to December 2017 were retrospectively included from 3 imaging centers in Hong Kong (HK). Stress perfusion CMR examinations were performed using either adenosine or adenosine triphosphate. Adequate stress was assessed by achieving splenic switch-off sign. Measurement of MPRI was performed in all stress perfusion CMR scans. Patients were followed for major adverse cardiovascular events defined as all-cause death, acute coronary syndrome (ACS), epicardial CAD development, heart failure hospitalization and non-fatal stroke. RESULTS: A total of 218 patients were studied (mean age 59 ± 12 years; 49.5% male) and the average MPRI of that cohort was 1.56 ± 0.33. Females and a history of hyperlipidemia were predictors of lower MPRI. Major adverse cardiovascular events (MACE) occurred in 15.6% of patients during a median follow-up of 5.5 years (interquartile range: 4.6 to 6.8 years). The optimal cutoff value of MPRI in predicting MACE was found with a threshold MPRI ≤1.47. Patients with MPRI ≤1.47 had three-fold increased risk of MACE compared with those with MPRI >1.47 (hazard ratio [HR]: 3.14; 95% confidence interval [CI]: 1.58 to 6.25; p = 0.001). Multivariate Cox regression after adjusting for age and hypertension demonstrated that MPRI was an independent predictor of MACE (HR: 0.10; 95% CI: 0.03 to 0.34; p < 0.001). CONCLUSIONS: Stress perfusion CMR-derived MPRI is an independent imaging marker that predicts MACE in patients with ischemic symptom and no overt CAD over the medium term.

Right ventricular mechanics and exercise capacity in patients with microvascular angina: The impact of microvascular function.

OBJECTIVES: We planned to assess the right ventricular mechanics in subjects with typical chest pain and angiographically normal coronary arteries (microvascular angina [MVA]) and to search for an association between right ventricular mechanics, coronary flow reserve, and exercise tolerance. METHODS: Seventy-one patients with MVA (mean age of 48.5 ± 7.9 years, 63% female) and 30 healthy control subjects were recruited. Right ventricular mechanics were calculated utilizing speckle tracking imaging. The exercise capacity was assessed by metabolic equivalents (METs). Coronary flow reserve (CFR) was calculated as the ratio between hyperemic (in response to intravenous adenosine) diastolic peak flow velocity and the basal diastolic peak velocity. RESULTS: Coronary flow reserve (a surrogate marker of microvascular dysfunction) was diminished in MVA patients compared with the control group (2.41 ± 0.35 vs 3.35 ± 0.5; P < .03). Patients with lower right ventricular global longitudinal strain (RVGLS) and right ventricular global longitudinal strain rate (RVGLSr) had a considerably lower CFR (P < .001) and a significantly lower MET (P < .001) than patients with normal RV mechanics. Right ventricular global longitudinal strain and RVGLSr were significantly correlated with both CFR and METs in subjects with MVA. Receiver operating characteristic (ROC) curve analysis demonstrated that RVGLS ≤ -14.5 was the best cutoff value for the prediction of impaired exercise tolerance in patients with MVA. CONCLUSION: We suggested that impaired right ventricular mechanics in subjects with microvascular angina was associated with reduced exercise capacity. Moreover, right ventricular mechanics is significantly correlated with coronary flow reserve. Henceforth, right ventricular mechanics might be of value for both risk stratification and follow-up in cases with microvascular dysfunction.

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.

Diagnosis of Microvascular Angina Using Cardiac Magnetic Resonance.

BACKGROUND: In patients with angina and nonobstructive coronary artery disease (NOCAD), confirming symptoms due to coronary microvascular dysfunction (CMD) remains challenging. Cardiac magnetic resonance (CMR) assesses myocardial perfusion with high spatial resolution and is widely used for diagnosing obstructive coronary artery disease (CAD). OBJECTIVES: The goal of this study was to validate CMR for diagnosing microvascular angina in patients with NOCAD, compared with patients with obstructive CAD and correlated to the index of microcirculatory resistance (IMR) during invasive coronary angiography. METHODS: Fifty patients with angina (65 ± 9 years of age) and 20 age-matched healthy control subjects underwent adenosine stress CMR (1.5- and 3-T) to assess left ventricular function, inducible ischemia (myocardial perfusion reserve index [MPRI]; myocardial blood flow [MBF]), and infarction (late gadolinium enhancement). During subsequent angiography within 7 days, 28 patients had obstructive CAD (fractional flow reserve [FFR] ≤0.8) and 22 patients had NOCAD (FFR >0.8) who underwent 3-vessel IMR measurements. RESULTS: In patients with NOCAD, myocardium with IMR <25 U had normal MPRI (1.9 ± 0.4 vs. controls 2.0 ± 0.3; p = 0.49); myocardium with IMR ≥25 U had significantly impaired MPRI, similar to ischemic myocardium downstream of obstructive CAD (1.2 ± 0.3 vs. 1.2 ± 0.4; p = 0.61). An MPRI of 1.4 accurately detected impaired perfusion related to CMD (IMR ≥25 U; FFR >0.8) (area under the curve: 0.90; specificity: 95%; sensitivity: 89%; p < 0.001). Impaired MPRI in patients with NOCAD was driven by impaired augmentation of MBF during stress, with normal resting MBF. Myocardium with FFR >0.8 and normal IMR (<25 U) still had blunted stress MBF, suggesting mild CMD, which was distinguishable from control subjects by using a stress MBF threshold of 2.3 ml/min/g with 100% positive predictive value. CONCLUSIONS: In angina patients with NOCAD, CMR can objectively and noninvasively assess microvascular angina. A CMR-based combined diagnostic pathway for both epicardial and microvascular CAD deserves further clinical validation.

Non-invasive assessment of microvascular dysfunction in patients with microvascular angina.

BACKGROUND: We aimed to evaluate the microvascular function in patients with microvascular angina (MVA) by assessing 1) the endothelial glycocalyx barrier properties using sublingual microscopy, and 2) the myocardial perfusion reserve using cardiovascular magnetic resonance (CMR) imaging. METHODS: Sublingual microscopy was performed in 13 MVA patients (angina pectoris, ST-depression on treadmill testing, normal coronary angiogram) and compared with 2 control groups of 13 volunteers and 14 patients with known obstructive coronary artery disease (CAD). To test the glycocalyx-mediated microvascular responsiveness, the erythrocyte perfused boundary region (PBR) was assessed at baseline and after nitroglycerin challenge. RESULTS: The baseline PBR of MVA patients was similar to controls with CAD (p=0.72), and larger than in volunteers (p=0.02). Only the volunteers demonstrated a significant increase in PBR after nitroglycerin (p=0.03). In the 13 MVA patients, adenosine stress CMR perfusion imaging was performed. Although a significant increase in myocardial perfusion was observed in both the subendocardium and subepicardium during stress, the subendocardial perfusion reserve was significantly lower (p=0.02). The PBR responsiveness of the sublingual microvasculature showed a strong correlation with the transmural myocardial perfusion reserve (r=0.86, p<0.001). CONCLUSIONS: Patients with MVA can be characterized by microvascular glycocalyx dysfunction using sublingual microscopy. The strong correlation between sublingual PBR responsiveness and myocardial perfusion reserve suggests that the glycocalyx may play an important role in the regulation of microvascular volume for myocardial perfusion and supports the concept of impaired glycocalyx barrier properties in MVA.

Left atrial volume and function in patients with cardiac syndrome X assessed by real time three-dimensional echocardiography.

OBJECTIVE: The aim of this study was to evaluate left atrial (LA) volume and function using real time three-dimensional echocardiography (RT3DE) in patients with cardiac syndrome X (CSX). METHODS: Fifty patients with CSX (28 females; mean age 50.9±10.9 years) and 50 age- and gender-matched healthy controls (30 females; mean age 52.3±9.8 years) who had negative treadmill exercise test and normal coronary arteries on invasive coronary angiography were included in the study. Comprehensive two-dimensional (2D), pulsed and tissue Doppler, speckle tracking echocardiography, and RT3DE for the assessment of LA dynamics were performed in all study participants. RESULTS: Cardiac syndrome X and control groups have similar clinical characteristics regarding age, sex, body mass index, hypertension, diabetes, and smoking habit. 2D echocardiographic parameters were also similar between groups. Pulsed- and tissue Doppler parameters, IVRT, A, and Am values, were higher in CSX group, while Em , E/A, and Em /Am ratios were higher in the control group reflecting mild diastolic dysfunction. Regarding RT3DE parameters, LA maximum volume, minimum volume, volume before atrial contraction, LA maximum volume index, total and active stroke volumes were found to be increased in CSX patients. However, LA total stroke fraction, passive stroke volume, passive stroke fraction, peak systolic, and diastolic longitudinal strains were found to be lower in CSX patients. CONCLUSION: The main finding of this study was that CSX patients had altered LA booster pump, reservoir, and conduit functions. This finding may have clinical implications for early detection of abnormal LA dynamics in CSX patients.

Coronary Microvascular Function and Cardiovascular Risk Factors in Women With Angina Pectoris and No Obstructive Coronary Artery Disease: The iPOWER Study.

BACKGROUND: The majority of women with angina-like chest pain have no obstructive coronary artery disease when evaluated with coronary angiography. Coronary microvascular dysfunction is a possible explanation and associated with a poor prognosis. This study evaluated the prevalence of coronary microvascular dysfunction and the association with symptoms, cardiovascular risk factors, psychosocial factors, and results from diagnostic stress testing. METHODS AND RESULTS: After screening 3568 women, 963 women with angina-like chest pain and a diagnostic coronary angiogram without significant coronary artery stenosis (<50%) were consecutively included. Mean age (SD) was 62.1 (9.7). Assessment included demographic and clinical data, blood samples, questionnaires, and transthoracic echocardiography during rest and high-dose dipyridamole (0.84 mg/kg) with measurement of coronary flow velocity reserve (CFVR) by Doppler examination of the left anterior descending coronary artery. CFVR was successfully measured in 919 (95%) women. Median (IQR) CFVR was 2.33 (1.98-2.76), and 241 (26%) had markedly impaired CFVR (<2). In multivariable regression analysis, predictors of impaired CFVR were age (P<0.01), hypertension (P=0.02), current smoking (P<0.01), elevated heart rate (P<0.01), and low high-density lipoprotein cholesterol (P=0.02), but these variables explained only a little of the CFVR variation (r(2)=0.09). CFVR was not associated with chest pain characteristics or results from diagnostic stress testing. CONCLUSION: Impaired CFVR was detected in a substantial proportion, which suggests that coronary microvascular dysfunction plays a role in the development of angina pectoris. CFVR was associated with few cardiovascular risk factors, suggesting that CFVR is an independent parameter in the risk evaluation of these women. Symptom characteristics and results from stress testing did not identify individuals with impaired CFVR.

Altered transmural contractility in postmenopausal women affected by cardiac syndrome X.

BACKGROUND: Cardiac syndrome X (CSX) is characterized by typical angina and abnormal exercise test results, with normal coronary arteries. Cardiovascular magnetic resonance imaging has shown subendocardial hypoperfusion in patients with CSX after adenosine. The aim of this study was to investigate the contribution of separate myocardial layers to global function under stress in women with CSX. METHODS: Twenty-two postmenopausal women with CSX were studied and compared with 20 healthy women matched for age and body mass index. All subjects underwent clinical evaluations and exercise echocardiography. Left ventricular systolic and diastolic parameters were evaluated at rest and at peak exercise. Layer-specific global longitudinal strain (GLS) and strain rate (SR) were assessed from the endocardium, midmyocardium, and epicardium using two-dimensional speckle-tracking echocardiography. RESULTS: All subjects showed normal contractile function at rest and at peak exercise. Significant increases in GLS and SR in all myocardial layers were observed at peak exercise in the control group, whereas patients with CSX showed significantly lower increases in endocardial GLS and SR compared with the control group (endocardial ΔSR, 0.17 ± 0.19 vs 0.33 ± 0.13 [P < .01]; endocardial ΔGLS, 1.33 ± 2.93 vs 6.64 ± 2.62 [P < .001]). Moreover, significantly impaired diastolic function (ΔE', 1.1 ± 3.3 vs 4.0 ± 2.03) was observed in patients with CSX. CONCLUSIONS: The results of this study show subendocardial impairment of contractile function during exercise in patients with CSX, confirming the existence of reduced myocardial perfusion reserve in patients with CSX and suggesting layer-targeted exercise echocardiography as a sensitive diagnostic tool in the assessment of suspected CSX.

Prevalence of metabolic syndrome, insulin resistance, and microvascular angina pectoris in 500 consecutive patients referred to coronarography.

OBJECTIVE: This work was aimed to evaluate the prevalence of insulin resistance (IR) and metabolic syndrome in a large cohort of 40-60 years old patients with cardiovascular symptoms. METHODS: A total of 500 consecutive males and females referred to coronarography and coronary catheterization, because of spontaneous or after load precordial pain plus denivelisation of ST segment by electrocardiography, were included. Besides standard clinical examinations, ergometry, echocardiography, fundamental laboratory tests, and several other laboratory examinations were also performed, including oral glucose toleration test (OGTT), total and high-density lipoprotein (HDL) cholesterol, triglycerides, apoprotein A1 and B, apolipoprotein (a), uric acid, fibrinogen, plasminogen activator inhibitor-1 (PAI-1), cytokines (tumor necrosis factor α, TNFα, interleukin-1, IL-1, interleukin-6, IL-6), endothelin-1, as well as hormones (insulin, C peptide, leptin, growth hormone, cortisol). RESULTS: In 81.6% of patients, IR syndrome with compensatory hyperinsulinemia was found in a positive correlation with various symptoms of metabolic syndrome, including abdominal obesity, increased body mass index (BMI), dysglycemia, dyslipoproteinemia, coronary stenosis, decreased HDL level, and hypertension. Hirsutism with polycystic ovarian syndrome was found in 52% of examined women with IR. However, a normal coronary angiogram, called as a microvascular form of the angina pectoris (MIV-AP), was found in 14% of predominantly periclimacteric and benign hirsutic females with long-term disorders of menstrual cycle. Since these patients showed the same symptoms as their gender, age, BMI, and degree of coronary stenoses adjusted pairs with the macrovascular form (such as the same levels of several lipids, hormones and obesity measures), our data strongly support the view that MIV-AP might belong to the IR syndrome. CONCLUSIONS: Hyperinsulinemia and high prevalence of various symptoms of metabolic syndrome (MS) were found in high percentage of patients with after load precordial pain who were referred to coronarography. Similarly, in several women, MIV-AP was detected and its affiliation to MS suggested.

Coronary microvascular function and cortical pain processing in patients with silent positive exercise testing and normal coronary arteries.

ST-segment depression during exercise stress testing in asymptomatic subjects showing normal coronary arteries is considered a "false-positive" result. Coronary microvascular dysfunction, however, might be a possible cause of ST-segment depression in these cases. We assessed the coronary blood flow response to adenosine and to cold pressor test in the left anterior descending artery, using transthoracic Doppler echocardiography in 14 asymptomatic subjects with exercise-induced ST-segment depression and normal coronary arteries (group 1), 14 patients with microvascular angina (group 2), and 14 healthy subjects (group 3). Flow-mediated dilation was assessed in the brachial artery. Central pain processing was assessed using cortical laser evoked potentials during chest and right hand stimulation with 3 sequences of painful stimuli. The coronary blood flow response to adenosine was 1.8 ± 0.4, 1.9 ± 0.5, and 3.1 ± 0.9 in groups 1, 2, and 3, respectively (p <0.001). The corresponding coronary blood flow responses to the cold pressor test were 1.74 ± 0.4, 1.53 ± 0.3, and 2.3 ± 0.6 (p <0.001). The flow-mediated dilation was 5.5 ± 2.3%, 4.6 ± 2.4%, and 9.8 ± 1.2% in the 3 groups, respectively (p <0.001). The laser evoked potential N2/P2 wave amplitude decreased throughout the 3 sequences of stimulation in groups 1 and 3 but not in group 2 (chest, -19 ± 22%, +11 ± 42% and -36 ± 12%, p <0.001; right hand, -22 ± 25%, +12 ± 43% and -30 ± 20%, p = 0.009; in groups 1, 2, and 3). In conclusion, exercise stress test-induced ST-segment depression in asymptomatic subjects with normal coronary arteries cannot be considered as a simple false-positive result, because it can be related to coronary microvascular dysfunction. The different symptomatic state compared to patients with microvascular angina can, at least in part, be explained by differences in cortical processing of neural pain stimuli.

Relation between cardiovascular risk factors and coronary microvascular dysfunction in cardiac syndrome X.

BACKGROUND: The causes of coronary microvascular dysfunction (CMVD) in patients with cardiac syndrome X (CSX) are largely unknown. Common cardiovascular risk factors (CVRFs) and increased markers of inflammation have been associated with CMVD in some studies, but their role in determining CMVD in CSX patients remains poorly known. METHODS AND RESULTS: We studied 71 CSX patients (56 ± 9 years, 23 men) and 20 healthy volunteers (52 ± 7 years, nine men). Using transthoracic Doppler echocardiography, coronary microvascular vasodilator function was assessed in the left anterior descending coronary artery as the ratio of diastolic coronary blood flow (CBF) velocity at peak intravenous adenosine administration and during cold pressor test (CPT) to the respective basal CBF velocity values. Common CVRFs tended to be more frequent and C-reactive protein (CRP) levels were higher (P < 0.001) in CSX patients than in controls. Both CBF responses to adenosine (2.05 ± 0.6 vs. 2.92 ± 0.9, P < 0.001) and to CPT (1.71 ± 0.6 vs. 2.42 ± 0.7, P < 0.001) were lower in CSX patients than in controls. The differences between the two groups in CBF response to adenosine and in CBF response to CPT remained highly significant (P < 0.01 for both) after adjustment for all CVRFs, including serum CRP levels. CONCLUSION: In CSX patients, both endothelium-dependent and endothelium-independent CMVD cannot be reliably predicted by CVRFs (including serum CRP levels), alone or in combination.

Cardiac adrenergic nerve function and microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVE: To assess whether abnormalities in cardiac uptake of (123)I-metaiodobenzylguanidine (MIBG) correlate with coronary microvascular dysfunction in patients with cardiac syndrome X (CSX). SETTING: University hospital. PATIENTS: 29 patients (aged 59 (SD 7) years, 11 men) with typical CSX and a matched group of 20 healthy subjects (aged 56 (7) years, 8 men) were studied. INTERVENTIONS: Planar and single photon emission computed tomography (SPECT) MIBG myocardial scintigraphy was performed in all subjects. Coronary flow response (CFR) to adenosine and to cold pressor test (CPT) in the left anterior descending (LAD) coronary artery was assessed in all CSX patients and in 12 controls by transthoracic Doppler echocardiography. MAIN OUTCOME MEASURES: Abnormalities in cardiac MIBG scintigraphy were observed in 25 CSX patients (86.2%), but in no healthy control (p<0.001). Compared to controls, CSX patients showed a lower heart/mediastinum (H/M) ratio of MIBG uptake (1.69 (0.24) vs 2.2 (0.3), p<0.001) and a higher cardiac MIBG defect score (25 (22) vs 4 (2), p = 0.002). Both CFR to adenosine (3.31 (1.1) vs 1.94 (0.6), p<0.001) and CFR to CPT (2.35 (0.5) vs 1.63 (0.4), p<0.001) were lower in CSX patients than in controls. In CSX patients, however, no correlation was found between MIBG H/M ratio and CFR to adenosine (r = 0.17; p = 0.38) and to CPT (r = -0.28; p = 0.13), as well as between MIBG uptake score in the LAD territory and CFR to adenosine (r = 0.14; p = 0.47) and to CPT (r = 0.06; p = 0.73). CONCLUSION: Our data show striking abnormalities in cardiac adrenergic nerve function and in coronary microvascular function in CSX patients. However, no significant relation between the two abnormalities was found. Further studies are needed to clarify the mechanisms and the role of MIBG defects in CSX patients.

Outcomes in patients with abnormal myocardial perfusion imaging and normal coronary angiogram.

A subset of subjects undergoing myocardial perfusion imaging has perfusion abnormalities that are subsequently labeled false positive based on coronary angiography. We evaluated the long-term prevalence of cardiovascular events in these patients. We retrospectively identified 48 patients who had reversible perfusion abnormalities with myocardial perfusion imaging and normal coronary angiography. Patients with known coronary artery disease, left ventricular dysfunction, valvular disease, and cardiomyopathy were excluded. Patient follow-up, conducted for at least 3 (mean interval, 7.4) years from the index myocardial perfusion imaging, was accomplished by a review of medical records and telephone interviews. Study endpoints were cardiovascular events defined as sudden cardiac death, myocardial infarction, percutaneous coronary revascularization, coronary artery bypass grafting, and cerebrovascular or peripheral revascularization. Thirty-one percent (15 of 48) of the patients had cardiovascular events. Six of the 48 patients had coronary events. These patients had abnormal myocardial perfusion imaging and normal coronary angiogram. The time between myocardial perfusion imaging and coronary event was 0.5 to 8.67 years. There was a strong correlation between the regions of original perfusion abnormality and the ultimate coronary ischemia or revascularization. Abnormal findings on myocardial perfusion imaging may predict a higher prevalence of coronary and peripheral vascular events than suggested by a normal coronary angiogram.

Relation between stress-induced myocardial perfusion defects on cardiovascular magnetic resonance and coronary microvascular dysfunction in patients with cardiac syndrome X.

OBJECTIVES: The purpose of this study was to investigate whether a direct relation can be demonstrated between myocardial perfusion defects detected during dobutamine stress test (DST) by cardiovascular magnetic resonance (CMR) and impairment of coronary microvascular dilatory function in patients with cardiac syndrome X (CSX). BACKGROUND: Despite the fact that coronary microvascular dysfunction has been shown in most patients with CSX, the ischemic origin of CSX remains debated. No previous study assessed whether a strict relation exists between abnormalities in myocardial perfusion and coronary microvascular dysfunction in CSX patients. METHODS: Eighteen CSX patients (mean age 58 +/- 7 years, 7 men) and 10 healthy control subjects (mean age 54 +/- 8 years, 4 men) underwent myocardial perfusion study by gadolinium-enhanced CMR at rest and at peak DST (maximal dose 40 microg/kg/min). Coronary flow response (CFR) to adenosine (140 microg/kg/min in 90 s) in the left anterior descending (LAD) coronary artery was assessed by high-resolution transthoracic echo-Doppler and expressed as the ratio between coronary flow velocity at peak adenosine and at rest. RESULTS: At peak DST, reversible perfusion defects on CMR were found in 10 CSX patients (56%) but in none of the control subjects (p = 0.004). The CFR to adenosine in the LAD coronary artery was lower in CSX patients than in control subjects (2.03 +/- 0.63 vs. 3.29 +/- 1.0, p = 0.0004). The CSX patients with DST-induced myocardial perfusion defects in the LAD territory on CMR had a lower CFR to adenosine compared with those without perfusion defects in the LAD territory (1.69 +/- 0.5 vs. 2.31 +/- 0.6, p = 0.01). A significant correlation was found in CSX patients between CFR to adenosine and a DST perfusion defect score on CMR in the LAD territory (r = -0.45, p = 0.019). CONCLUSIONS: Our data concurrently show DST-induced myocardial perfusion defects on CMR and reduced CFR in the LAD coronary artery territory in CSX patients, thus giving strong evidence that a dysfunction of coronary microcirculation resulting in myocardial perfusion abnormalities is present in these patients.

Noninvasive evaluation of flow reserve in the left anterior descending coronary artery in patients with cardiac syndrome X.

Data on coronary flow reserve (CFR) in patients with syndrome X are still controversial. Further, noninvasive evaluation of epicardial and microvascular flow reserves in these patients has never been performed. In 17 patients with syndrome X and in 17 age- and gender-matched control subjects, CFR in the mid left anterior descending coronary artery (LAD) was evaluated by transthoracic color and pulse-wave Doppler using a 7-mHz probe (Sequoia, Siemens). Peak diastolic LAD flow was calculated at rest and at peak adenosine (140 microg/kg/min intravenously in 90 seconds). Myocardial contrast echocardiography (MCE) was performed at rest and during adenosine use by real-time cadence pulse sequencing and intravenous SonoVue (Bracco; 5 ml at 1 ml/min) and microvascular blood volume (A), velocity (beta), and flow (Axbeta) by replenishing curves (y = A[1 - e(betat)]). CFR was measured by Doppler echocardiography as an adenosine/rest velocity ratio and by MCE as a microvascular volume, velocity, and flow adenosine/rest ratio. Compared with controls, patients with syndrome X demonstrated lower LAD CFR and velocity and flow microvascular flow reserves (p <0.01, <0.005, and <0.005, respectively). In patients with syndrome X, those with angina and ST-segment depression during adenosine testing had even lower LAD CFR and velocity and flow microvascular flow reserves compared with those with no symptoms (p <0.0001, <0.0001, and <0.005, respectively). LAD CFR demonstrated a significant linear correlation with velocity microvascular flow reserve (r = 0.92, p <0.0001) and flow microvascular flow reserve (r = 0.77, p <0.0001). In conclusion, CFR in the LAD, successfully evaluated by transthoracic Doppler echocardiography and MCE, is significantly decreased in patients with syndrome X and even more in those with angina pectoris and ST-segment depression during adenosine testing. Thus, noninvasive evaluation of CFR by echocardiography is feasible and provides information on the severity of microvascular impairment.