Peak Diastolic Coronary Flow Velocity Research Articles

Anatomical, functional and prognostic correlates of resting coronary flow velocity in patients with hypertrophic cardiomyopathy

Abstract Background The clinical significance of baseline peak diastolic coronary flow velocity (CFV) in the left anterior descending coronary artery (LAD) has not been investigated yet in patients with hypertrophic cardiomyopathy (HCM). Aim To assess the anatomical, functional and prognostic correlates of baseline LAD CFV in HCM. Methods 384 consecutive adult HCM patients (age=52+15 years, 164 [43%] females) with no known coronary artery disease from 8 centers in 5 countries were prospectively analyzed. All patients underwent comprehensive transthoracic echocardiography including CFV measurement with pulse wave Doppler in the mid-distal LAD. All patients had preserved left ventricular (LV) function. LV force was calculated as (peak instantaneous LV outflow tract gradient+systolic blood pressure)/LV end-systolic volume. Patients were followed for a median of 50 months (IQ range 18-97 months), the outcome measure was a composite endpoint of all-cause death and acute heart failure. Results The mean CFV was 36±11 cm/s. CFV was positively correlated with LV maximal wall thickness (r=0.375, p<0.001), LV maximal septal thickness (r=0.320, p<0.001), resting LV outflow tract gradient (r=0.274, p<0.001), LV force (r=0.227, p<0.001), mean E/e’ (r=0.479, p<0.001) and heart rate (r=0.221, p<0.001). During follow-up, 54 events occurred (33 all-cause deaths and 21 acute heart failures). Receiver operating characteristic analysis was used to determine the best cut-off value of CFV (>31 cm/s) to predict the composite endpoint. Patients with CFV >31 cm/s had a significantly worse 10-year event-free survival compared to those with CFV ≤31 cm/s, see Figure. Conclusion Higher resting LAD CFV is associated with greater LV wall thickness, higher LV outflow tract gradient, faster heart rate and more elevated left ventricular filling pressures in HCM. Elevated resting CFV may indicate a coronary microcirculation dysfunction either primary or secondary to anatomical (septal hypertrophy), functional (increased myocardial oxygen demand), or autonomic (increased sympathetic drive) determinants. Whatever the underlying endotype, high resting CFV is related to worse prognosis in the long term.Figure.

Coronary Flow Evaluation in Heart Transplant Patients Compared to Healthy Controls Documents the Superiority of Coronary Flow Velocity Reserve Companion as Diagnostic and Prognostic Tool.

BackgroundDistinct contributions by functional or structural alterations of coronary microcirculation in heart transplantation (HT) and their prognostic role have not been fully elucidated. We aimed to identify the mechanisms of coronary microvascular dysfunction (CMD) in HT and their prognostic implications.Methods134 patients, surviving at least 5 years after HT, without evidence of angiographic vasculopathy or symptoms/signs of rejection were included. 50 healthy volunteers served as controls. All underwent the assessment of rest and hyperemic coronary diastolic peak flow velocity (DPVr and DPVh) and coronary flow velocity reserve (CFVR) and its inherent companion that is based on the adjusted quadratic mean: CCFVR = √{(DPVr)2 + (DPVh)2}. Additionally, basal and hyperemic coronary microvascular resistance (BMR and HMR) were estimated.ResultsBased on CFVR and DPVh, HT patients can be assigned to four endotypes: endotype 1, discordant with preserved CFVR (3.1 ± 0.4); endotype 2, concordant with preserved CFVR (3.4 ± 0.5); endotype 3, concordant with impaired CFVR (1.8 ± 0.3) and endotype 4, discordant with impaired CFVR (2.0 ± 0.2). Intriguingly, endotype 1 showed lower DPVr (p < 0.0001) and lower DPVh (p < 0.0001) than controls with lower CFVR (p < 0.0001) and lower CCFVR (p < 0.0001) than controls. Moreover, both BMR and HMR were higher in endotype 1 than in controls (p = 0.001 and p < 0.0001, respectively), suggesting structural microvascular remodeling. Conversely, endotype 2 was comparable to controls. A 13/32 (41%) patients in endotype 1 died in a follow up of 28 years and mortality rate was comparable to endotype 3 (14/31, 45%). However, CCFVR was < 80 cm/s in all 13 deaths of endotype 1 (characterized by preserved CFVR). At multivariable analysis, CMD, DPVh < 75 cm/s and CCFVR < 80 cm/s were independent predictors of mortality. The inclusion of CCFVR < 80 cm/s to models with clinical indicators of mortality better predicted survival, compared to only adding CMD or DPVh < 75 cm/s (p < 0.0001 and p = 0.03, respectively).ConclusionA normal CFVR could hide detection of microvasculopathy with high flow resistance and low flow velocities at rest. This microvasculopathy seems to be secondary to factors unrelated to HT (less rejections and more often diabetes). The combined use of CFVR and CCFVR provides more complete clinical and prognostic information on coronary microvasculopathy in HT.

Specific impact of cardiovascular risk factors on coronary microcirculation in patients with subclinical hypothyroidism.

BackgroundAlthough thyroid hormones have significant effect on cardiovascular system, the impact of subtle thyroid dysfunction such as subclinical hypothyroidism (SCH) remains to be determined. We investigated coronary flow reserve (CFR) in patients with subclinical hypothyroidism.MethodsThirty two subjects with SCH and eighteen control subjects with normal serum thyroid hormones and thyroid-stimulating hormone (TSH) levels were included in the study. TSH, free thyroxine, free triiodothyronine, glucose, insulin, HbA1c, cholesterol, triglyceride and plasma levels of C-reactive protein were measured. Coronary diastolic peak flow velocities in left anterior descending coronary artery were measured at baseline and after adenosine infusion. CFR was calculated as the ratio of hyperemic to baseline diastolic peak velocity.ResultsCFR values were not significantly different between the two groups (SCH 2.76±0.35 vs controls 2.76±0.42). There was a significant correlation of CFR with waist to hip ratio, hypertension, smoking habits, markers of glucose status (glucose level, HbA1c, insulin level, HOMA IR), cholesterol, LDL-cholesterol and triglyceride levels in SCH group, whereas only cholesterol level showed significant correlation with CFR in controls. There was no correlation between CFR and thyroid hormones.ConclusionsWe concluded that there is a different impact of cardiovascular risk factors on CFR in SCH patients compared to healthy control and that these two groups behave differently in the same circumstances under the same risk factors. The basis for this difference could be that the altered thyroid axis "set point" changes the sensitivity of the microvasculature in patients with SCH to known risk factors.

Comparison of coronary flow reserve feasibility and values in different stress echocardiography protocols: dobutamine, dipyridamole, exercise and rapid pacing

Abstract Background and aims To compare the feasibility of Coronary Flow Velocity Reserve (CFVR) assessment in the left anterior descending (LAD) artery in four types of stress echocardiography (SE): dobutamine (DOB), dipyridamole (DIP), rapid pacing (PAC) and bicycle exercise (EXE). Methods and results We subjected 369 patients (mean age: 67±11 years) to SE with DOB (up to 40 mcg/kg/min, n=230), DIP (0.84 mg/kg, n=73), PAC (n=22) or EXE (n=44). CFVR was measured as the ratio of peak diastolic coronary flow velocity (CFV) during exercise, pharmacological stress or pacing and peak diastolic CFV at rest in distal or mid LAD. The feasibility was excellent during PAC (100%), DOB (95%) and DIP (95%) and lower during EXE (73%, p&amp;lt;0.01 vs other groups) when assessed in all consecutive patients. When assessed in patients having readable LAD flow at rest the feasibility achieved even higher values, being however still lowered in EXE group, see Figure 1. In multivariate analysis only the EXE protocol was a predictor of LAD flow loss during SE, with OR = 8.23 (95% CI 2.17 – 31.33), p=0.0019. CFVR was lower with PAC (1.8±0.4) as compared to DIP (2.2±0.6, p=0.0061) and DOB (2.2±0.6, p=0.0025), but similar to EXE (2.0±0.6, p=0.178), and correlated best with the peak heart rate in EXE and PAC, see Figure 2. Conclusion CFVR in LAD can be obtained during all forms of SE, but the feasibility is significantly higher with PAC and pharmacological tests as compared to EXE, which was identified in our study as the independent predictor of the loss of LAD flow recording at the peak of stress test. Moreover, CFVR values were the lowest in PAC group which however encompassed the older patients with more advanced coronary artery disease. Significant correlation between HR and CFVR observed in EXE and PAC suggests that in this type of SE cut-off value of CFVR should be probably indexed to maximal HR achieved. Funding Acknowledgement Type of funding sources: None. Figure 1Figure 2

Comparison of coronary flow reserve feasibility in different stress echocardiography protocols: dobutamine, dipyridamole, exercise, and rapid pacing.

The assessment of coronary flow velocity reserve (CFVR) may improve the diagnostic and prognostic value of stress echocardiography (SE). The aim of the study was to compare the feasibility of CFVR assessment in the left anterior descending artery (LAD) in 4 modalities of SE: dobutamine, dipyridamole, rapid cardiac pacing, and exercise using cycle ergometer. We performed SE in 369 patients (mean [SD] age, 67 [11] years) with dobutamine (n = 230), dipyridamole (n = 73), rapid cardiac pacing (n = 22), or exercise (n = 44) between June 2017 and June 2020. We measured CFVR as the ratio of peak diastolic coronary flow velocity during exercise, pharmacological stress, or pacing to peak diastolic coronary flow velocity at rest in the distal or mid LAD. The feasibility of CFVR was excellent during rapid cardiac pacing (100%), dobutamine (95%), and dipyridamole (95%) and was lower during exercise (73%; P <⁠0.01 vs other groups). In multivariable analysis, the exercise protocol was a predictor of the loss of blood flow in the LAD during SE (odds ratio, 7.89; 95% CI, 2.17–31.33; P = 0.002). The median (interquartile range) CFVR was lower with rapid cardiac pacing (1.7 [1.4–2.0]) as compared with dobutamine (2.1 [1.7–2.5]), dipyridamole (2.1 [1.8–2.5]), and exercise (2.0 [1.7–2.3]) (P <⁠0.05 for all). CFVR in the LAD can be obtained during all forms of SE, but the feasibility is significantly higher with rapid cardiac pacing and pharmacological tests as compared with exercise, which was identified in our study as an independent predictor of the loss of blood flow during a blood flow recording in the LAD at the peak of stress test.

Reversible impairment of coronary flow reserve in acute myocarditis.

Acute myocarditis is accompanied by an impaired coronary microcirculation. These microcirculatory disturbances are not well defined, and data are derived from complex invasive measurements. Therefore, this study aimed to evaluate the inflammation-induced microcirculatory dysfunction including its reversibility and association with markers of inflammation severity (extent of LGE on CMR imaging and laboratory markers of myocardial necrosis) using the noninvasive technique of echocardiographic CFR measurement. Patients (n=14) with clinically suspected acute myocarditis in the absence of coronary artery disease were prospectively enrolled, and echocardiographic CFR was determined by measuring peak diastolic coronary blood flow velocity at rest (PDV1) and under adenosine-induced hyperemia (PDV2) at baseline and 3-month follow-up. Eight of 14 (57.1%) patients showed an impaired baseline CFR (PDV2/PDV1<2). These patients were characterized by higher levels of cardiac troponin T (0.55±0.39 vs 0.18±0.08; P=0.008) and larger areas of LGE on CMR. At 3-month follow-up, CFR was normal in all patients. A reversibly impaired coronary microcirculation is a frequent finding in acute myocarditis and is associated with markers of inflammation severity. Echocardiographic CFR measurement represents a feasible and safe method for its assessment.

Development of Isolated Diastolic Dysfunction Associated with Early Impairment in Coronary Blood Flow in Hypertensive Diabetes

While diabetes mellitus and hypertension are independent risk factors for development of cardiomyopathy and coronary artery disease, little data are available regarding coronary blood flow dysfunction in the early hypertensive diabetic heart. The present study investigated changes in coronary flow in hypertensive diabetic animals and its relation to cardiac function in the early stage of diabetes. Since angiotensin II (Ang II) contributes to both diabetes and hypertension we also assessed the activities of two major enzymes involved in Ang II formation (angiotensin converting enzyme; ACE) and degradation (ACE2). Diabetes was induced in male spontaneously hypertensive rats (SHR) by a single injection of streptozotocin (STZ: 65 g/kg, i.p.; n=7). Age matched male SHR served as controls (CTL: n=6). Cardiac structure, systolic and diastolic function, and left coronary artery peak diastolic coronary flow velocity were evaluated by transthoracic echocardiography in anesthetized rats using the VevoLAZR imaging system two weeks after STZ injection. ACE and ACE2 activities were assessed by HPLC in plasma membranes isolated from the left ventricle. When compared to control animals, blood glucose was higher (470 ± 26 vs 126 ± 3 mg/dL; p&lt;0.01) whereas thickness of the left ventricular posterior (1.57 ± 0.09 vs 2.04 ± 0.10 mm; p&lt;0.01) and anterior (1.34 ±0.05 vs 1.93 ± 0.08 mm; p&lt;0.01) walls and relative wall thickness (0.46 ± 0.3 vs 0.60 ± 0.03; p&lt;0.01) were reduced in diabetic hypertensive animals. Two weeks of hyperglycemia did not affect arterial pressure in diabetic hypertensive rats (179 ± 5 vs 170 ± 4 mmHg; p=NS) while it markedly reduced left coronary artery peak diastolic flow velocity (235 ± 47 vs 460 ± 38 mm/s). Despite high blood pressure and reduced wall thickness, cardiac systolic function assessed by fractional shortening (46 ± 1 vs 49 ± 2 %; p=NS) and ejection fraction (76 ± 1 vs 79 ± 2 %; p=NS) remained unchanged. In contrast, significant diastolic impairment reflected in decreased tissue velocity of mitral annulus (28 ± 1 vs 57 ± 2 mm/s; p&lt;0.01) and increased filling pressure (30 ± 1 vs 22 ± 1; p&lt;0.01) was observed in the early stages of STZ‐induced diabetes. While ACE2 activity was decreased in left ventricles of diabetic SHR (17.62 ± 0.53 vs 20.01 ± 0.32 fmol/mg/min; p&lt;0.01), there was no change in cardiac ACE activity between the two groups (4.21 ± 0.36 vs 4.50 ± 0.62 fmol/mg/min; p=NS). Our results suggest that impaired early coronary flow dynamics associated with decreased cardiac ACE2 activity might contribute to the development of isolated diastolic dysfunction in diabetic hypertensive rats independent of blood pressure.Support or Funding InformationP01‐HL051592This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Coronary Flow Velocity Reserve in Burn Injury: A Prospective Clinical Cohort Study.

The authors sought to evaluate coronary microvascular function and left ventricular diastolic dysfunction using transthoracic Doppler echocardiography in burn patients. In this study, 32 adult burn patients with partial or full-thickness scald burns that were hospitalized and treated were included. The control group was matched for age and sex and was composed of otherwise healthy volunteers. Transthoracic Doppler echocardiography examinations and simultaneous laboratory tests for cardiac evaluation were performed on the sixth month after burn injury as well as with the control group. High-sensitivity C-reactive protein levels were significantly higher in the burn patients than in controls (5.17 ± 3.86 vs 2.42 ± 1.78; P = .001). Lateral isovolumic relaxation time was significantly higher in the burn injury group than in the control group (92.7 ± 15.7 vs 85.5 ± 8.3; P = .03). Baseline coronary diastolic peak flow velocity of the left anterior descending artery was similar in both groups. However, hyperemic diastolic peak flow velocity and coronary flow velocity reserve (2.26 ± 0.48 vs 2.94 ± 0.47; P < .001) were significantly lower in the burn injury group than in the control group. Coronary flow velocity reserve was significantly and inversely correlated with high-sensitivity C-reactive protein, burn ratio, creatinine, and mitral A-wave max velocity. At the sixth month of treatment, burn patients had high-sensitivity C-reactive protein levels during this period, suggesting that inflammation still exists. In addition, subclinical coronary microvascular and left ventricular diastolic dysfunction can occur in burn patients without traditional cardiovascular risk factors. However, these results must be supported by additional studies.

Left Bundle Branch Block Negatively Affects Coronary Flow Velocity Reserve and Myocardial Contractile Reserve in Nonischemic Dilated Cardiomyopathy

Coronary flow velocity reserve (CFVR) of the left anterior descending coronary artery (LAD) and myocardial contractile reserve are often impaired in nonischemic dilated cardiomyopathy (DCM). Whether they are affected by the presence of left bundle branch block (LBBB) remains unaddressed. The aim of the study was to investigate how LBBB influences CFVR of the LAD and myocardial contractile reserve in patients with DCM. One hundred eighty-one patients with DCM (116 men; mean age, 63±12years) underwent high-dose dipyridamole (0.84mg/kg over 6min) stress echocardiography with CFVR evaluation of the LAD by Doppler. All patients had ejection fractions<40% (mean, 31±8%) and angiographically normal or near normal coronary arteries. CFVR was defined as the ratio between hyperemic peak and basal peak diastolic coronary flow velocities. CFVR>2.0 was considered normal. Inotropic reserve was defined as rest-stress variation in wall motion score index≥0.20. This was a prospective analysis of an unselected sample consecutively enrolled and retrospectively selected. The study group was separated on the basis of presence (n=122) or absence (n=59) of LBBB. Patients with LBBB were older (64±11 vs 59±12 years, P=.004) and had reduced resting ejection fractions (30±9% vs 33±7%, P=.02), CFVR of the LAD (1.96±0.41 vs 2.23±0.73, P=.001), and myocardial contractile reserve (variation in wall motion score index, -0.18±0.17 vs -0.33±0.28; P<.001). On multivariate logistic regression analysis, resting ejection fraction (hazard ratio [HR], 1.15; 95% CI, 1.03-1.29; P=.01), smoking habit (HR, 2.63; 95% CI, 1.23-5.62; P=.01), and LBBB (HR, 2.29; 95% CI, 1.05-5.04; P=.04) were independently associated with reduced CFVR, while restrictive transmitral pattern (HR, 2.56; 95% CI, 1.18-5.55; P=.02), end-diastolic volume (HR, 0.98; 95% CI, 0.67-0.99; P=.02), and LBBB (HR, 2.20; 95% CI, 1.11-4.34; P=.02) independently predicted reduced myocardial contractile reserve. CFVR during vasodilator stress echocardiography is a suitable tool for assessing microvascular dysfunction in routine clinical practice. Patients with DCM and LBBB show more severe forms of microvascular dysfunction, which is related to worse left ventricular function and lack of contractile reserve. Therapeutic interventions to restore microvascular function may improve left ventricular function parameters in patients with DCM.

Abstract O.57: Coronary Circulation Assessed by Transthoracic Echocardiography during Exercise Test is Impaired in Patients after Kawasaki Disease Even with Regressed Coronary Arterial Lesions

Background: Coronary flow reserve (CFR) has important clinical implications for the evaluation of coronary circulation including Kawasaki disease (KD). Pharmacological vasodilation is generally used to induce hyperemia for the assessment of CFR; however, exercise test provides more physiological stress. Objectives: This study sought to assess CFR during exercise in patients after KD with regressed coronary arterial lesions (CALs) by transthoracic echocardiography (TTE). Methods: Twenty KD patients were studied, comprising 8 patients with regressed CALs in the left anterior descending coronary artery (LAD) and 12 patients without CALs (median ages; 10 and 9 years, respectively). Fourteen age-matched healthy subjects were also studied as controls. We obtained peak diastolic coronary flow velocity (CFV) of the LAD by pulsed-Doppler TTE at rest and at submaximal exercise on supine ergometer. CFR was calculated as the ratio of exercise to rest CFVs. Results: The CFV measurements were obtained in all the subjects. There was no significant difference in the CFVs among the patients with regressed CALs, those without CALs and the controls (30 ± 7 vs. 31 ± 10 vs. 28 ± 8 cm/s, respectively). The CFVs increased during exercise in the patients without CALs and the controls (51 ± 11 and 49 ± 10 cm/s, respectively, both p &lt;0.05). In consequence, the CFR was lower in the patients with regressed CALs compared with those without CALs and the controls (1.3 ± 0.2 vs. 1.7 ± 0.2 and 1.7 ± 0.2, respectively, p &lt;0.05). Conclusions: Exercise test demonstrated impaired CFR in KD patients with regressed CALs. It suggests that these patients have risk of future myocardial ischemic events.

Coronary Flow Velocity Reserve in Patients with Ascending Aorta Aneurysm

Ascending aorta aneurysms (AAA) are one of the leading causes of morbidity and mortality. Impairment in coronary flow may contribute to cardiovascular consequences in AAA patients. Coronary flow velocity reserve (CFVR) has been considered an important diagnostic index of the functional capacity of coronary arteries noninvasively. The aim of this study was to evaluate, by noninvasive CVFR, whether patients with AAA demonstrate significant coronary microvascular dysfunction in the absence of coronary artery disease (CAD). We prospectively included 44 patients with thoracic AAA in the absence of concomitant CAD (30 men, 14 women; mean age 57.5±8.4years). A total of 36 patients without aortic dilatation (mean age 55.2±9.9years) were selected as the control group. Coronary flow velocities in the distal left anterior descending (LAD) artery were measured using transthoracic echocardiography. CFVR was calculated as the hyperemic to resting coronary diastolic peak velocities ratio. Compared with controls, patients with AAA had higher baseline LAD peak diastolic coronary flow velocities (28.3±5.8 vs. 25.2±4.5cm/sec, P=0.01), lower hyperemic LAD flow velocities (54.0±10.3 vs. 57.2±12.7cm/sec, P=0.220), and consequently lower CFVR (1.9±0.3 vs. 2.3±0.5, P<0.001). Multivariate linear regression analysis showed that CFVR was independently associated only with aortic systolic diameter (AoSD) (β=-0.679, P=<0.001). Our study demonstrates that noninvasive CFVR is significantly reduced in patients with AAA and AoSD is the most important determinant of impaired CFVR.

Evaluation of coronary microvascular function and nitric oxide synthase intron 4a/b polymorphism in patients with coronary slow flow

Slow coronary flow (SCF) is reported to be associated with increased risk of cardiovascular disease. We have used coronary flow reserve measurement by transthoracic Doppler echocardiography to determine coronary microvascular function in patients with SCF and to determine whether the intron 4a/b polymorphism of the eNOS gene influences coronary endothelial function. Overall, 96 patients with SCF and 79 controls were enrolled in the study. Coronary flow was quantified according to the thrombolysis in myocardial infarction (TIMI) frame count (TFC) on angiogram. Coronary diastolic peak flow velocities (DPFV) were measured with color Doppler flow mapping at baseline and after dipyridamole infusion. Coronary flow reserve was calculated as the ratio of hyperemic to baseline DPFV. The eNOS 4a/b polymorphism was detected by PCR. Patients with diabetes were excluded from the study. The SCF group was comparable to the control group in terms of demographic and clinical characteristics, except for hemoglobin and HDL-cholesterol levels, TFC of the left anterior descending artery, the circumflex artery, and the right coronary artery; the mean TFC was higher in the SCF group. Hyperemic DPFV and the hyperemic/baseline DPFV ratio were significantly lower in the SCF group when compared with the control group. However, baseline DPFV were similar in both groups. The number of patients with eNOS4 a/a and eNOS4 a/b phenotypes was statistically higher in SCF groups. The frequency of allele 'a' of the eNOS4 gene was also statistically higher in the SCF group. When patients were grouped according to the presence or absence of allele 'a' of the eNOS4 gene, statistically significant differences were found in the TFC of the left anterior descending artery, the circumflex artery; mean TFC; baseline DPFV; and hyperemic/baseline DPFV. Univariate analysis in which eNOS4 b/b was used as the referent group showed that the presence of allele 'a' of the eNOS4 gene significantly predicted SCF (odds ratio: 2.79, 95% confidence interval: 1.32-5.89; P=0.007). In multivariate analysis using a model adjusted for variables with a P value lower than 0.10 in univariate analyses, the presence of allele 'a' of the eNOS4 gene was found to be an independent predictor of SCF (odds ratio: 3.22, 95% confidence interval: 1.28-8.82; P=0.013). The presence of allele 'a' may be a risk factor for microvascular endothelial dysfunction and higher TFCs in SCF patients.

Flow in the Left Anterior Descending Coronary Artery in Patients With Migraine Headache

Migraine is a common neurovascular disorder characterized by attacks of severe headache, autonomic and neurologic symptoms. Migraine can affect many systems in the body, yet its effects on cardiovascular system are unclear. We hypothesized that migraine and coronary microvascular angina may be manifestations of a common systemic microvascular dysfunction and clinically associated. Forty patients with migraine and 35 healthy volunteers were included into the study. Using transthoracic Doppler echocardiography, coronary flow was visualized in the middle or distal part of the left anterior descending artery. Coronary diastolic peak flow velocities were measured with pulse wave Doppler at baseline and after dipyridamole infusion (0.56 mg/kg/4 min). Coronary flow reserve of <2 was considered normal. In addition, thorough 2-dimensional and Doppler echocardiographic examinations were also performed. Fifty-two women and 23 men were included. Coronary flow reserve was significantly lesser in the migraine group than in the control group (1.99 ± 0.3 vs 2.90 ± 0.5, p <0.05). In addition, mitral annular velocities were lower and the ratio of early mitral inflow velocity to early mitral annular velocity (E/E' lateral and E/E' septal) was higher in migraineurs than in the control group (p <0.05 for all), indicating diastolic function abnormalities in the migraine group. In conclusion, these findings suggest that there is an association between coronary microvascular dysfunction and migraine independently of the metabolic state of the patients. A common pathophysiologic pathway of impaired endothelial vasodilatation, vasomotor dysfunction, and increased systemic inflammatory factors may play a role in these 2 clinical conditions and could be the underlying cause of subclinical systolic and diastolic left ventricular dysfunction in migraineurs.

Impaired coronary flow reserve is associated with increased echocardiographic epicardial fat thickness in metabolic syndrome patients

Metabolic syndrome (MetS) is a strong predictor of cardiovascular events and coronary flow reserve (CFR), an indicator of microvascular function, has been found to be impaired in MetS. Epicardial fat thickness (EFT) reflects visceral adiposity and is considered an important cardiometabolic marker. In this study, we aimed to examine the presence of an association between CFR and EFT in MetS patients. Forty-six MetS patients (25 men, mean age 47.3±6.6 years) and 44 age-matched and sex-matched controls (24 men, mean age 46.0±6.1 years) were prospectively studied. Both CFR and EFT were measured by transthoracic echocardiography. Peak diastolic coronary flow velocities were measured in the left anterior descending artery by pulsed wave Doppler at the baseline and after adenosine infusion, and CFR was calculated as the ratio of hyperemic to baseline velocities. The waist circumference, total and low-density lipoprotein-cholesterol, fasting glucose, triglycerides, systolic and diastolic blood pressures, and high sensitive C-reactive protein were significantly higher in MetS patients. The mean EFT was significantly higher in MetS patients compared with the controls (8.7±0.2 vs. 4.8±0.1 mm, P<0.001); however, CFR was significantly lower in MetS patients (2.3±0.2 vs. 2.7±0.2, P<0.001). CFR was correlated significantly with BMI, waist circumference, high-density lipoprotein-cholesterol, triglycerides, fasting glucose, high sensitive C-reactive protein, and EFT. In regression analysis, MetS itself and EFT were found to be independent predictors of impaired CFR. CFR is impaired in MetS patients. MetS itself and increased EFT are associated independently with coronary microvascular dysfunction and EFT is a predictor of worse CFR even after accounting for the presence or absence of the MetS.

Impaired Coronary Microvascular Function and Its Association with Disease Duration and Inflammation in Patients with Psoriasis

Thirty-six patients with psoriasis and 56 healthy volunteers were included in this study. Echocardiographic examination included transmitral peak flow velocities of the early phase (E) and late phase (A) of the mitral inflow, left ventricular myocardial velocity measurements, and coronary flow reserve (CFR) measurement. Baseline coronary diastolic peak flow velocity (DPFV) of left anterior descending artery (LAD) was significantly higher in the psoriasis group. However, hyperemic DPFV was slightly lower and CFR (2.19±0.39 vs. 2.60±0.31, P<0.0001) was significantly lower in the psoriasis group than in the control group. CFR was significantly and inversely correlated with disease duration, Psoriasis Area and Severity Index (PASI) score, and hsCRP. CFR is decreased in patients with psoriasis, and it correlates to disease duration, PASI score, and inflammation.

Non-Invasive Detection of Coronary Endothelial Response to Sequential Handgrip Exercise in Coronary Artery Disease Patients and Healthy Adults

ObjectivesOur objective is to test the hypothesis that coronary endothelial function (CorEndoFx) does not change with repeated isometric handgrip (IHG) stress in CAD patients or healthy subjects.BackgroundCoronary responses to endothelial-dependent stressors are important measures of vascular risk that can change in response to environmental stimuli or pharmacologic interventions. The evaluation of the effect of an acute intervention on endothelial response is only valid if the measurement does not change significantly in the short term under normal conditions. Using 3.0 Tesla (T) MRI, we non-invasively compared two coronary artery endothelial function measurements separated by a ten minute interval in healthy subjects and patients with coronary artery disease (CAD).MethodsTwenty healthy adult subjects and 12 CAD patients were studied on a commercial 3.0 T whole-body MR imaging system. Coronary cross-sectional area (CSA), peak diastolic coronary flow velocity (PDFV) and blood-flow were quantified before and during continuous IHG stress, an endothelial-dependent stressor. The IHG exercise with imaging was repeated after a 10 minute recovery period.ResultsIn healthy adults, coronary artery CSA changes and blood-flow increases did not differ between the first and second stresses (mean % change ±SEM, first vs. second stress CSA: 14.8%±3.3% vs. 17.8%±3.6%, p = 0.24; PDFV: 27.5%±4.9% vs. 24.2%±4.5%, p = 0.54; blood-flow: 44.3%±8.3 vs. 44.8%±8.1, p = 0.84). The coronary vasoreactive responses in the CAD patients also did not differ between the first and second stresses (mean % change ±SEM, first stress vs. second stress: CSA: −6.4%±2.0% vs. −5.0%±2.4%, p = 0.22; PDFV: −4.0%±4.6% vs. −4.2%±5.3%, p = 0.83; blood-flow: −9.7%±5.1% vs. −8.7%±6.3%, p = 0.38).ConclusionMRI measures of CorEndoFx are unchanged during repeated isometric handgrip exercise tests in CAD patients and healthy adults. These findings demonstrate the repeatability of noninvasive 3T MRI assessment of CorEndoFx and support its use in future studies designed to determine the effects of acute interventions on coronary vasoreactivity.

Impaired coronary flow reserve evaluated by echocardiography is associated with increased aortic stiffness in patients with metabolic syndrome: an observational study

Metabolic syndrome (MetS) is a strong predictor of cardiovascular events and coronary flow reserve (CFR), an indicator of microvascular function, has been found to be impaired in MetS. Aortic stiffness (AS) is a simple and effective method for assessing arterial elasticity. The aim of this study was to evaluate whether there is an independent association of impaired coronary flow and aortic elasticity in patients with MetS. Forty-six patients (mean age 47.3 ± 6.6 years) with the diagnosis of MetS according to the ATP III update criteria and 44 age and gender matched controls (mean age 46.0 ± 6.1 years) were included into the cross-sectional observational study. Peak diastolic coronary flow velocities were measured in left anterior descending artery by pulsed wave Doppler at baseline and after adenosine infusion, and CFR was calculated as the ratio of hyperemic to baseline velocities. Aortic strain, distensibility and stiffness were calculated by M-mode echocardiography. Statistical analysis was performed by using Student t-test, Chi-square test, Pearson correlation and linear regression analyses. CFR was significantly lower in patients with MetS than in controls (2.3 ± 0.2 vs 2.7 ± 0.2, p<0.001). In the MetS group, aortic distensibility (10.4 ± 3.5 cm².dyn⁻¹.10⁻⁶ vs. 12.7 ± 3.4 cm2.dyn⁻¹.10⁻⁶, p=0.002) was decreased and AS was significantly increased (6.5 ± 2.0 vs. 3.2 ± 0.8, p<0.001). In multivariate linear regression analysis, AS (β=-0.217, p=0.047), systolic blood pressure (β=-0.215, p=0.050) and waist circumference (β=-0.272, p=0.012) had an independent relationship with impaired CFR. This study demonstrated that coronary flow reserve is impaired in patients with MetS and there is an independent relationship between impaired CFR and increased aortic stiffness, systolic blood pressure or waist circumference.

Possible further reduction in coronary flow velocity reserve in angina pectoris patients after oral glucose loading.

Previous studies have suggested an increase in myocardial oxygen demand as a cause of postprandial angina. The purpose of this study was to assess coronary flow velocity reserve (CFVR) in the left anterior descending coronary artery (LAD) before and after glucose ingestion in patients with known significant LAD stenosis. Fourteen patients with significant LAD stenosis and 20 subjects without LAD stenosis were enrolled. Transthoracic Doppler echocardiography was performed to measure the average peak diastolic coronary flow velocity (APDV) in the LAD at rest and during adenosine infusion. CFVR was calculated as APDV during adenosine infusion (APDVATP) divided by APDV at rest (APDVrest). APDVrest, APDVATP, and CFVR were assessed during fasting and 30, 60, and 120min after a 75-g oral glucose loading. In patients with LAD stenosis, APDVrest at 30min after glucose loading was the highest at any time point. However, significant differences were not found in the APDVATP among time points in the patients or controls. Consequently, the CFVR in the patients was the lowest at 30min after glucose loading (fasting, 1.77±0.19; 30min, 1.48±0.16; 60min, 1.69±0.17; and 120min, 1.76±0.19; p<0.01, ANOVA), as in the controls. These findings suggested that the value of CFVR in the LAD was reduced after glucose loading. Myocardial risk area supplied by a stenosed coronary artery may be exposed to myocardial ischemia more frequently during oral glucose loading than during fasting in patients with significant coronary artery stenosis.

Measurement of the coronary flow velocity reserve in patients with non-alcoholic fatty liver disease

Endothelial dysfunction is an early and reversible feature in the pathogenesis of atherosclerosis. Coronary flow velocity reserve is a noninvasive test showing endothelial function of epicardial coronary arteries and coronary microcirculatory function. This study was designed to evaluate the carotid intima-media thickness and myocardial microvascular circulation in patients with non-alcoholic fatty liver disease. Twenty-four patients with non-alcoholic fatty liver disease and 28 healthy subjects were studied. According to the pathology of liver biopsies, patients with non-alcoholic fatty liver disease were divided into non-alcoholic fatty liver and nonalcoholic steatohepatitis groups. Coronary diastolic peak flow velocities were measured at baseline, and then dipyridamole infusion was measured by transthoracic Doppler echocardiography. The ratio of hyperemic to baseline diastolic peak velocities was calculated and the intima-media thicknesss of the carotid arteries were measured. Baseline average diastolic peak and diastolic mean flow velocities were similar between non-alcoholic fatty liver disease patients and healthy subjects. However, hyperemic average diastolic peak and diastolic mean flow velocities were significantly lower in the patient groups compared to those in the controls (p=0.005 and p=0.002). Coronary flow velocity reserve was 1.65 ± 0.36 and 2.67 ± 0.81 in patients and healthy subjects, respectively (p < 0.001). The intima-media thickness was similar between the patients with non-alcoholic fatty liver disease and healthy subjects. The comparison of patients with non-alcoholic fatty liver and non-alcoholic steatohepatitis within the non-alcoholic fatty liver disease group with respect to coronary flow velocity reserve and intima-media thickness yielded no statistical differences. The present study showed that coronary flow velocity reserve, which establishes coronary microvascular and endothelial functions noninvasively, is significantly impaired in patients with non-alcoholic fatty liver disease. The impaired coronary flow velocity reserve-like early atherosclerotic changes may have value in the prediction of coronary artery disease in patients with non-alcoholic fatty liver disease.

Association between Serum Total Antioxidant Status and Coronary Microvascular Functions in Patients with SLE

Mortality from cardiovascular disease has been found to be increased in patients with systemic lupus erythematosus (SLE). Coronary flow reserve (CFR) measurement is used both to assess epicardial coronary arteries and to examine the integrity of coronary microvascular circulation. Oxidative stress, enhancing modification of plasma lipids, is also associated with atherosclerotic events in lupus patients. Impairment of CFR and TAS has been shown to be an early manifestation of coronary atherosclerosis. Forty patients with SLE and 33 healthy volunteers were included in this study. Echocardiographic examination included left ventricular myocardial velocity measurements and coronary flow reserve (CFR) measurement. Serum total antioxidant status levels (TAS) also were measured using TAS kit. Lateral myocardial early peak velocity (Em) and lateral Em/Am ratio did not differ between the groups, but lateral myocardial atrial peak velocity (Am) was significantly higher in SLE group than the control group. Baseline coronary diastolic peak flow velocity (DPFV) of left anterior descending was similar in both the groups. However, hyperemic DPFV and CFR (2.50 ± 0.42 vs. 3.09 ± 0.45, P < 0.0001) were significantly lower in the SLE group than in the control group. CFR significantly and inversely correlated with CRP and significantly correlated with TAS. Subclinical coronary microvascular dysfunction can occur in SLE patients without traditional cardiovascular risk factors, probably associated with underlying inflammation and impairment of TAS.