Coronary Microvascular Dysfunction In Patients Research Articles

Functional Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With ST-Segment Elevation Myocardial Infarction.

The aim of this study was to evaluate the diagnostic accuracy and prognostic implications of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with ST-segment elevation myocardial infarction (STEMI). The index of microcirculatory resistance (IMR) is a reliable invasive measure of coronary microvascular dysfunction in patients with STEMI. A functional coronary angiography-derived method to estimate IMR is a wire- and hyperemic agent-free alternative to IMR. The study population consisted of 2 independent cohorts. The diagnostic cohort comprised patients with IMR from the culprit vessel immediately after successful primary percutaneous coronary intervention (n=31). The prognostic cohort was patients with STEMI who were successfully treated with primary percutaneous coronary intervention and followed for 10 years from the index procedure (n=309). Angio-IMR was calculated using computational flow and pressure simulation. The primary outcome was a composite of cardiac death and readmission for heart failure over 10 years of follow-up. In the diagnostic cohort, angio-IMR correlated well with IMR (R=0.778; P< 0.001). Sensitivity, specificity, accuracy, and area under the curve of angio-IMR to predict IMR >40 U were 75.0%, 84.2%, 80.6%, and 0.899 (95% confidence interval: 0.786-0.949), respectively. In the prognostic cohort, patients with angio-IMR >40 U showed significantly higher risk for cardiac death or readmission for heart failure than did those with angio-IMR≤40 U (46.7% vs 16.6%; adjusted hazard ratio: 2.909; 95%CI: 1.670-5.067; P< 0.001). Angio-IMR >40 U was an independent predictor of cardiac death or readmission for heart failure (hazard ratio: 2.173; 95%CI: 1.157-4.079; P=0.016) and showed incremental prognostic value compared with a model with clinical risk factors only (C index=0.726 vs 0.666 [P< 0.001], net reclassification index=0.704 [P< 0.001]). Angio-IMR showed high correlation and diagnostic accuracy to predict IMR. Patients with STEMI with angio-IMR >40 U showed a significantly higher risk for cardiac death or readmission for heart failure than those with preserved angio-IMR values. (Prognostic Implication of Angiography-Derived IMR in STEMI Patients; NCT04628377).

Prevalence of Coronary Artery Disease and Coronary Microvascular Dysfunction in Patients With Heart Failure With Preserved Ejection Fraction

Coronary artery disease (CAD) and coronary microvascular dysfunction (CMD) may contribute to the pathophysiologic characteristics of heart failure with preserved ejection fraction (HFpEF). However, the prevalence of CAD and CMD have not been systematically studied. To examine the prevalence of CAD and CMD in hospitalized patients with HFpEF. A total of 106 consecutive patients hospitalized with HFpEF were evaluated in this prospective, multicenter, cohort study conducted between January 2, 2017, and August 1, 2018; data analysis was performed from March 4 to September 6, 2019. Participants underwent coronary angiography with guidewire-based assessment of coronary flow reserve, index of microvascular resistance, and fractional flow reserve, followed by coronary vasoreactivity testing. Cardiac magnetic resonance imaging was performed with late gadolinium enhancement and assessment of extracellular volume. Myocardial perfusion was assessed qualitatively and semiquantitatively using the myocardial-perfusion reserve index. The prevalence of obstructive epicardial CAD, CMD, and myocardial ischemia, infarction, and fibrosis. Of 106 participants enrolled (53 [50%] women; mean [SD] age, 72 [9] years), 75 had coronary angiography, 62 had assessment of coronary microvascular function, 41 underwent coronary vasoreactivity testing, and 52 received cardiac magnetic resonance imaging. Obstructive epicardial CAD was present in 38 of 75 participants (51%, 95% CI, 39%-62%); 19 of 38 (50%; 95% CI, 34%-66%) had no history of CAD. Endothelium-independent CMD (ie, coronary flow reserve <2.0 and/or index of microvascular resistance ≥25) was identified in 41 of 62 participants (66%; 95% CI, 53%-77%). Endothelium-dependent CMD (ie, abnormal coronary vasoreactivity) was identified in 10 of 41 participants (24%; 95% CI, 13%-40%). Overall, 45 of 53 participants (85%; 95% CI, 72%-92%) had evidence of CMD and 29 of 36 (81%; 95% CI, 64%-91%) of those without obstructive epicardial CAD had CMD. Cardiac magnetic resonance imaging findings included myocardial-perfusion reserve index less than or equal to 1.84 (ie, impaired global myocardial perfusion) in 29 of 41 patients (71%; 95% CI, 54%-83%), visual perfusion defect in 14 of 46 patients (30%; 95% CI, 19%-46%), ischemic late gadolinium enhancement (ie, myocardial infarction) in 14 of 52 patients (27%; 95% CI, 16%-41%), and extracellular volume greater than 30% (ie, diffuse myocardial fibrosis) in 20 of 48 patients (42%; 95% CI, 28%-56%). Patients with obstructive CAD had more adverse events during follow-up (28 [74%]) than those without obstructive CAD (17 [46%]). In this cohort study, 91% of patients with HFpEF had evidence of epicardial CAD, CMD, or both. Of those without obstructive CAD, 81% had CMD. Obstructive epicardial CAD and CMD appear to be common and often unrecognized in hospitalized patients with HFpEF and may be therapeutic targets.

Prognostic impact of coronary microvascular dysfunction in patients with myocardial infarction with non-obstructive coronary arteries

BackgroundMyocardial infarction with non-obstructive coronary arteries (MINOCA) has been and remained a puzzling heterogeneous entity. The index of microcirculatory resistance (IMR) is a quantitative and specific index for the assessment of microvascular function. However, the role of IMR in MINOCA has not yet been studied. This study aimed to evaluate the prognostic value of coronary microvascular function, as assessed by coronary angiography‑derived index of microvascular resistance (caIMR) in MINOCA patients. MethodThis study included 109 MINOCA patients. Microvascular function was assessed by caIMR and was analyzed in 280 coronary arteries. The primary endpoint of the study was MACE, defined as cardiovascular death, nonfatal MI, heart failure, stroke and angina rehospitalization. The best cut-off of caIMR was derived from ROC analysis based on MACE prediction. ResultsThe patients were classified into high caIMR (caIMR>43U) and low caIMR (caIMR≤43U) based on a caIMR cut-off value of 43U. High caIMR was observed in 55 (50.5%) patients. A total of 27 MACE occurred during the 2 years of follow-up. MACE rate was significantly higher in patients with high caIMR than in patients with low caIMR (36.4% vs 13.0%, P=0.005). The Kaplan–Meier curves showed a significantly increased risk of MACE in patients with high caIMR (log-rank P=0.001). Cox multivariate analysis showed that caIMR>43 was a highly independent predictor of MACE (HR, 3.08; 95% CI, 1.13 - 8.35; P=0.027). ConclusionscaIMR is a strong predictor of clinical outcome among MINOCA patients. The evaluation of IMR can provide an objective risk stratification method for patients with MINOCA.

Impact of a micro-net mesh technology covering stent on coronary microvascular dysfunction in patients with high thrombus burden.

Highly thrombotic coronary lesions continue to be a serious and clinically significant problem that is not effectively and completely addressed by current technology. We aimed to investigate whether a micro-net mesh (MNM) technology covering stent could preserve the index of microcirculatory resistance (IMR) after percutaneous coronary intervention (PCI) in patients with high thrombus burden. Fifty-two patients with non-ST elevation myocardial infarction or ST Elevation Myocardial Infarction and high thrombus burden (TIMI thrombus grade ≥ 3) were randomized into two groups, PCI with a MNM covering stent (MNM group, n=25) and PCI with any commercially available stent (DES group, n=27). As the primary endpoint, IMR was measured immediately after PCI using a pressure-temperature sensor-tipped coronary wire. The secondary endpoint was left ventricular ejection fraction (LVEF) at 6 months of follow-up. The IMR in the MNM group was significantly lower in comparison to the DES group (33.2 [21.3, 48.9] vs. 57.2 [39.9, 98.0], p=0.005). No significant differences were observed in baseline LVEF (54.5 ± 10.2% vs. 53.1 ± 6.87%, p=.57), while LVEF was significantly improved at follow-up in the MNM group (61.1 ± 7.1% vs. 53.9 ± 6.35%, p=.0001). MNM technology significantly improved coronary microvascular dysfunction after PCI in patient with acute coronary syndrome and appears as a useful technological option for thrombus management.

Angiography-derived index of microcirculatory resistance (IMRangio) as a novel pressure-wire-free tool to assess coronary microvascular dysfunction in acute coronary syndromes and stable coronary artery disease.

To investigate the diagnostic accuracy of (1) hyperaemic angiography-derived index of microcirculatory resistance (IMRangio) in defining coronary microvascular dysfunction (CMD) across patients with acute coronary syndromes (ST-elevation myocardial infarction [STEMI]; non-ST elevation acute coronary syndrome [NSTE-ACS]) and stable chronic coronary syndrome [CCS]) and (2) the accuracy of non-hyperaemic IMRangio (NH-IMRangio) to detect CMD in STEMI. 145 patients (STEMI = 66; NSTEMI = 43; CCS = 36) were enrolled. 246 pressure-wire IMR measurements were made in 189 coronary vessels. IMRangio and NH-IMRangio was derived using quantitative flow ratio. In patients with STEMI, cardiac magnetic resonance was performed to quantify microvascular obstruction (MVO). IMRangio was correlated with IMR (overall rho = 0.78, p < 0.0001; STEMI, rho = 0.85 p < 0.0001; NSTE-ACS and rho = 0.72, p < 0.0001; CCS, rho = 0.70, p < 0.0001) and demonstrated good diagnostic performance in predicting high IMR (STEMI AUCROC = 0.93 [0.88-0.98]; NSTE-ACS AUCROC = 0.77 [0.63-0.92]; CCS AUCROC = 0.88 [0.79-0.97]). Agreement between the two indices was evident on Bland Altman analysis. In STEMI, NH-IMRangio was also well correlated with IMR (rho = 0.64, p < 0.0001), with good diagnostic accuracy in predicting high invasive IMR (AUCROC = 0.82 [0.74-0.90]). Both IMRangio (AUCROC = 0.74 [0.59-0.89]) and NH-IMRangio (AUCROC = 0.76 [0.54-0.87]) were significantly associated with MVO in STEMI. In conclusions, IMRangio is a valid alternative to invasive IMR to detect CMD in patients with acute and stable coronary syndromes, whilst NH-IMRangio has a good diagnostic accuracy in STEMI where it could become a user-friendly diagnostic tool as it is adenosine-free.

Standard exercise stress testing attenuates peripheral microvascular function in patients with suspected coronary microvascular dysfunction

BackgroundThe effect of exercise on the microvasculature of patients with suspected coronary microvascular dysfunction (CMD), assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT; EndoPAT), is unknown. The present study aimed to determine if standard clinical exercise stress testing (GXT) affected peripheral microvascular function, as determined by the reactive hyperemia index (RHI and LnRHI), in patients with suspected CMD.MethodsIn a cross-sectional study, patients (n = 76) were grouped based on whether the GXT was performed; 1) prior to (exercisers; n = 30), or 2) after the vascular assessment (non-exercisers; n = 46). Patients with an adenosine index of microvascular resistance > 25, adenosine coronary flow reserve (CFR) < 2.0, and/or acetylcholine CFR < 1.5 were considered to have CMD (n = 42). RHI and LnRHI quantified finger pulse amplitude hyperemia following 5 min of forearm ischemia.ResultsLnRHI was lower in patients with CMD compared to patients without CMD, while LnRHI was also lower in exercisers compared to non-exercisers (LnRHI: CMD Non-Exercisers: 0.63 ± 0.25; CMD Exercisers: 0.54 ± 0.19; No CMD Non-Exercisers: 0.85 ± 0.23; No CMD Exercisers: 0.63 ± 0.26; Condition and Exercise Main Effects: Both P < 0.01). In patients who did not exercise prior to the vascular assessment, the receiver operating characteristic curve (ROC) for LnRHI to predict CMD was 0.76 (95% CI: 0.62–0.91; P < 0.01). However, in patients who performed exercise prior to the vascular assessment, the ROC for LnRHI to predict CMD was 0.60 (95% CI: 0.40–0.81; P = 0.34).ConclusionsCMD is associated with impaired peripheral microvascular function and preceding acute exercise is associated with further reductions of LnRHI. Further, acute exercise abolished the capacity for RH-PAT to predict the presence of CMD in patients with chest pain and non-obstructive coronary arteries. RH-PAT measurements in patients with suspected CMD should not be conducted after exercise has been performed.

Elevated serum endothelin-1 is an independent predictor of coronary microvascular dysfunction in non-obstructive territories in patients with coronary artery disease.

Endothelin-1 contributes to the constrictor response of the coronary arteries in patients with ischemia with normal coronary arteries. There is thus increasing evidence that endothelin-1 plays a role in coronary microvascular dysfunction (CMD). We investigated whether elevated endothelin-1 is associated with CMD in patients with coronary artery disease (CAD). We prospectively studied 49 consecutive CAD patients with 1- or 2-vessel disease (age 71 ± 10 years, 43 males). Myocardial blood flow (MBF) was measured by 15O-water PET/CT at rest and during stress, and the coronary flow reserve (CFR) was calculated by dividing the stress MBF by the rest MBF. A CFR of less than 2.0 in non-obstructive regions was defined as a marker of CMD. Eighteen out of 49 (37%) CAD patients had CMD. Endothelin-1 in patients with CMD was significantly higher than in those without CMD (2.27 ± 0.81 vs. 1.64 ± 0.48pg/mL, P = 0.001). Accordingly, univariate ROC analysis showed that the continuous endothelin-1 levels significantly discriminated between the presence and absence of CMD (area under the curve = 0.746 [95%CI 0.592-0.899]). The dichotomous treatment of elevated endothelin-1 as 1.961pg/mL or more yielded the optimal discriminatory capacity, with a sensitivity of 72.2% and a specificity of 71.0%. High endothelin-1 was still a significant predictor of CMD after adjusting for diabetes mellitus (odds ratio = 6.64 [1.75-25.22], P = 0.005). Endothelin-1 is associated with CMD in non-obstructive territories in patients with CAD, suggesting that endothelin-1 is a potential target for treating CMD in CAD patients.

Impact of use stent with a polyethylene terephthalate micro-net covering on coronary microvascular dysfunction in patients with acute myocardial infarction

We aimed to investigate whether micro-net on stent could preserve the index of msicrocirculatory resistance (IMR) after primary percutaneous coronary intervention (PCI) in patients with acutemyocardial infarction (AMI). Fifty deux patients with AMI were randomized into two groups: primary PCI with micro-net on stent (MGUARD group, n = 25) and primary PCI with any commercially available (DES group, n = 27). As the primary endpoint, IMR was measured immediately after primary PCI using a pressure-temperature sensor-tipped coronary wire. The secondary endpoint was the left ventricular ejection fraction (LVEF) at six-month follow-up. The IMR in MGUARD group was significantly lower than in DES group (39.6 ± 26.2 U vs. 75.4 ± 60.5 U, P = 0.01). No significant differences in baseline EF (56.2 ± 10.3% vs. 54.9 ± 7.73%, P = 0.7), however, there were significant differences in follow-up EF (63.2 ± 3.8% vs. 54.7 ± 7.79%, P = 0.001). A micro-net on stent significantly improved CMVD compared with a traditional DES in primary PCI and appear as a useful technological option to manage the thrombus.

Relationship between malnutrition and coronary microvascular dysfunction in patients with nonischemic dilated cardiomyopathy

Background/ aimMalnutrition is common in patients with nonischemic dilated cardiomyopathy (DCM), especially in the end stages of the disease where heart failure symptoms predominate. Malnutrition has been associated with atherosclerosis in patients with chronic kidney disease, but it is unknown whether a similar relationship exists between malnutrition and coronary microvascular dysfunction (CMD). In the present study, we aimed to analyse whether indices of malnutrition were associated with coronary flow reserve (CFR) in patients with DCM.Materials and methodsA total of 33 cases who were prospectively followed up with by institutional DCM registry were found eligible for inclusion. Coronary flow reserve was measured with transthoracic echocardiography from the left anterior descending artery. The study sample was divided into 2 groups using a CFR cut-off value of 2.0. Geriatric nutritional index (GNI), prognostic nutritional index (PNI), and C-reactive protein/albumin ratio (CAR) were calculated.ResultsA total of 17 out of 33 cases (51.5%) had a low (<2.0) CFR. Both GNI and PNI were similar between the 2 groups, but the inflammatory–nutritional parameter CAR was significantly higher in those with a low CFR (1.18 ± 0.64 vs. 0.54 ± 0.28, P < 0.001). CA remained an independent predictor of CFR on multivariate regression (β = 0.65, P < 0.001) after adjustment for demographic (age, sex, body mass index), nutritional (GNI, PNI, albumin), and inflammatory (C-reactive protein) parameters. For a cut-off value of 0.80, CAR had a sensitivity of 85.7% and specificity of 73.6% to predict a CFR <2.0 (AUC: 0.835, 95%CI: 0.693–0.976, P = 0.001).ConclusionsOur findings indicate that not malnutrition per se but a combination of inflammation activation and malnutrition is predictive of CMD in patients with DCM.

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

ObjectiveAssociations 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).MethodsThe 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.ResultsUnivariate analyses showed that hMVRI correlated with age (β=0.24, p=0.007), eicosapentaenoic acid (EPA; β=-0.18, p=0.048), EPA/arachidonic acid (AA) (EPA/AA) ratio (β=-0.22, p=0.014) and CAVI (β=0.30, p=0.001). A multivariate regression analysis identified CAVI (β=0.25, p=0.007) and EPA/AA ratio (β=-0.26, SE=0.211, p=0.003) as independent determinants of hMVRI.ConclusionAortic 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.

Przepływ w gałęzi przedniej zstępującej lewej tętnicy wieńcowej u pacjentów z marskością wątroby

Introduction. Although cardiac function appears normal in patients with cirrhosis at rest, cardiac function deteriorates in these patients under stress conditions. Decreased cardiac function against stress may be due to coronary microvascular dysfunction in these patients. In this study, we aimed to evaluate coronary microvascular dysfunction in patients with cirrhosis by measuring coronary flow reserve (CFR) by transthoracic echocardiography. Materials and methods. Thirty-eight patients with cirrhosis and 32 healthy subjects (as control group) were examined. In addition to standard two-dimesional (2D) and Doppler echocardiography, coronary flow velocity was measured by pulsed-wave Doppler from the middle to the distal part of the left anterior descending artery at the beginning and after dipyridamole infusion in the hyperemic state. CFR was measured as the ratio of hyperemic peak diastolic flow rate to basal peak diastolic flow rate. Results. CFR was significantly lower in the cirrhosis group than in the control group (2.01 ± 0.31 and 2.84 ± 0.62; p Conclusions. Impaired CFR in patients with cirrhosis promotes coronary microvascular dysfunction. The coronary microvascular dysfunction can potentially contribute to the development of cirrhotic cardiomyopathy.

Abstract 14277: Serum Nt-prob-type Natriuretic Peptide is Associated With Coronary Microvascular Dysfunction in Patients With Angina and Non-obstructive Coronary Artery Disease

Title: Serum NT-proB-type Natriuretic Peptide is associated with Coronary Microvascular Dysfunction in Patients with Angina and Non-obstructive Coronary Artery Disease Authors: Ali Ahmad, MD, Jaskanwal D. Sara, MBChB, Michel T. Corban, MD, Takumi Toya, MD, Ilke Özcan, MD, Lilach O. Lerman, MD PhD, Amir Lerman, MD Introduction: Coronary microvascular dysfunction (CMD) is prevalent in patients with heart failure with preserved ejection fraction. Subclinical ischemia and myocardial fibrosis in CMD might raise filling pressure, a hallmark of HFpEF, which induces secretion of NT-proB-type natriuretic peptide (NTpro-BNP). We sought to explore the relationship between CMD and NT-proBNP. Methods: We studied 698 patients with signs and/or symptoms of ischemia and with non-obstructive CAD (&lt;40% angiographic stenosis) who underwent invasive CMD evaluation and had NT-proBNP checked within 6 weeks. CMD was defined as coronary flow reserve (CFR) (hyperemic flow/baseline flow as measured by the doppler wire) of ≤2.5 in response to intracoronary adenosine injection. Results: Overall mean age was 52.8±12.2 years, and women represented 69% of the patients. Log NT-proBNP showed a modest inverse correlation with CFR (Pearson’s R = -0.22, P&lt;0.0001; Figure 1 ), which remained significant after adjusting for age and gender (Standardized ß coefficient = -0.14; P = 0.001). Patients with CMD had higher levels of NT-proBNP than those without (82 [44-190] vs. 62 (33-130], P &lt;0.0001; Figure 2) . Conclusion: Declining coronary microvascular function is correlated with higher NT-proBNP levels. Patients with CMD had higher levels of NT-proBNP, a marker of elevated LV pressure, contributing to the possible role of CMD in early HFpEF pathophysiology. Keywords: Coronary microvascular dysfunction, NT-proBNP

Abstract 13792: Association of Immunocompromised State With Coronary Microvascular Dysfunction in Patients With Well-controlled HIV

Introduction: Patients with HIV have an elevated risk of cardiovascular disease (CVD) that may be partially driven by inflammation and residual immune dysfunction despite treatment with antiretroviral therapy (ART). Coronary microvascular dysfunction (CMD) is an important pathophysiological link between inflammation, immune dysfunction, and CVD and may provide mechanistic insight into CVD risk among HIV+ patients. Methods: We recruited 3 groups of adults aged 40-80 years free of CVD: HIV with evidence of prior/current immunocompromise (n=17), HIV without immunocompromise (n=19), and HIV- controls. All HIV+ participants were on ART and had suppressed viral loads. All controls were on HIV pre-exposure prophylaxis (PrEP). Immunocompromise was defined as nadir CD4 count &lt;200 cells/μL or current CD4 count &lt;500 cells/μL. Participants underwent Doppler echocardiography with coronary flow velocity measurement in the distal left anterior descending coronary artery at rest and during adenosine infusion. CMD was defined as coronary flow reserve (CFR) &lt; 2.50. Multivariable linear regression models assessed the association of HIV group with CFR. Results: Of 51 individuals who underwent CFR testing, median (IQR) age was 54 (46-58) and 92% were male. CFR was 3.71 (2.90-4.72) in controls, 3.49 (2.52-4.20) in HIV+/ immunocompromise-, and 2.35 (2.12-2.92) in HIV+/ immunocompromise+ (p=0.002). CMD was present in 7% of controls, 21% of HIV+/immunocompromise-, and 53% of HIV+/immunocompromise+ (p= 0.01). Compared with controls, HIV+/immunocompromise+ was significantly associated with lower CFR after multivariable adjustment ( Table ). Conclusions: HIV+ patients with current/prior immunocompromise free of CVD had high prevalence of CMD and had significantly lower CFR compared with controls on PrEP. Future studies should investigate CMD as a possible target for CVD prevention in HIV+ patients, particularly those with a prior or current immunocompromised state.

Coronary microvascular dysfunction in patients with mild-to-moderate aortic stenosis – Insights from intracoronary acetylcholine testing

Coronary microvascular dysfunction in patients with mild-to-moderate aortic stenosis – Insights from intracoronary acetylcholine testing

Higher serum angiopoietin 2 levels are independently associated with coronary microvascular dysfunction in patients with angina in the absence of obstructive coronary artery disease.

BackgroundAngiopoietin-2 (Ang-2) is a type of endothelial growth factor involved in angiogenesis and vascular remodeling. Circulating Ang-2 levels are elevated in patients with obstructive coronary artery disease (CAD). This study aimed to evaluate the association between serum Ang-2 levels and coronary microvascular dysfunction in patients without obstructive CAD.MethodsA total of 125 patients with angina in the absence of obstructive CAD were included in this cross-sectional study. Coronary flow reserve (CFR) was measured in the distal left anterior descending coronary artery by trans-thoracic Doppler echocardiography. The patients were divided into the following two sub-groups according to CFR: the impaired CFR group with CFR values <2.5 and the preserved CFR group with CFR values ≥2.5. Serum Ang-2 levels were determined using enzyme-linked immunosorbent assay. Independent predictors for impaired CFR were identified by binary logistic regression analysis. The receiver-operating characteristic curve was determined to evaluate the ability of serum Ang-2 in predicting impaired CFR.ResultsWe found that age, percentage of female sex, N-terminal pro-B-type natriuretic peptide levels, Ang-2 levels (763.3 ± 264.9 vs. 579.7 ± 169.3 pg/mL, P < 0.001), and the left atrial volume index were significantly higher in patients with impaired CFR than in patients with preserved CFR. Serum Ang-2 levels were negatively correlated with CFR (r = −0.386, P < 0.001). Binary logistic regression analysis showed that Ang-2 (odds ratio: 1.004, 95% confidence interval [CI]: 1.001–1.006, P = 0.003) and age (odds ratio: 1.088, 95% CI: 1.023–1.156, P = 0.007) were independently associated with impaired CFR. Furthermore, Ang-2 was a significant predictor of impaired CFR on the receiver-operating characteristic curve (P < 0.001). The area under the curve was 0.712 (95% CI: 0.612–0.813).ConclusionsHigh serum Ang-2 levels are independently associated with impaired CFR in patients with angina in the absence of obstructive CAD.

Correlation between longitudinal strain analysis and coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

The aim of this study was to evaluate in patients with microvascular angina and heart failure with preserved ejection fraction, the speckle-tracking echocardiography, and longitudinal myocardial strain to evaluate the possible presence of alterations in heart failure with preserved ejection fraction patients compared with a control population. We also investigated the correlation between the longitudinal strain analysis and the TIMI frame count after coronary angiography. Our study was performed on a population 41 patients with microvascular angina that underwent coronary angiography and speckle-tracking echocardiography. We divided the sample into two categories: patients with heart failure with preserved ejection fraction (n-21) and patients without heart failure with preserved ejection fraction (n-20). We calculated TIMI frame count indices for each patient based on angiographic images. Patients with heart failure with preserved ejection fraction had reduced global longitudinal strain values (-17.88) compared with the total control population, and this reduction was statistically significant (P=.028). This reduction was more marked in patients who had a significantly increased TIMI frame count. Therefore, a statistically significant correlation was observed between TIMI frame count and global longitudinal strain. Our results show that cardiac contractile mechanics are altered in patients with heart failure with preserved ejection fraction at a subclinical level hard to identifiable with conventional echocardiography. The dysfunction of the microcirculation and the consequent alteration of the TIMI frame count probably results in a reduction of myocardial performance.

Relationship Between Epicardial Fat Volume and Coronary Microvascular Dysfunction in Patients with Chest Pain and Unobstructed Coronary Arteries

Objective Epicardial fat (EF) is metabolically active adipose tissue positioned between the epicardial surface of the heart and the pericardium. We investigated whether there is a relationship between EF and Coronary Microvascular Dysfunction (CMD) in patients presenting with chest pain and unobstructed coronary arteries. Materials and Methods This study recruited patients referred to cardiology clinics for assessment of chest pain who subsequently underwent assessment via CT coronary angiogram (CTA). Myocardial blood flow reserve (MBFR) was assessed using myocardial contrast echocardiography. Epicardial fat volume (EFV) was measured by tracing serial slices on CTA with corresponding Hounsfield units of −195 to −45. Results We recruited 134 participants with a mean age of 59.2 (9.8) years. CMD was present in 54 (40%) patients, and the measured mean EFV was 128 mm3 (96, 168). Fortythree patients (32%) had a coronary artery calcium score (CACS) of 0, 64 (48%) had a CACS of 1–100, 18 (13%) had a CACS of 101–400, and 9 (7%) had a CACS >400. Univariate regression analysis showed that EFV and MBFR had a correlation coefficient of R=−0.22, with a significant regression slope (β=−0.002, p=0.012). Multivariable linear regression analysis using MBFR as a continuous outcome variable revealed age (β=−0.012, p=0.011) and CACS (β=−0.003, p=0.023) to be associated with MBFR. EFV was not associated with MBFR (β=−0.0007, p=0.538). Model repetition with MBFR as a dichotomous variable (MBFR ≥2 or <2) revealed no association with EFV. Conclusion No relationship was found between EFV and MBFR when traditional cardiovascular risk factors and calcium score.

Endothelium-dependent and independent coronary microvascular dysfunction in patients with heart failure with preserved ejection fraction.

Coronary microvascular inflammation is hypothesized to play a fundamental role in the pathophysiology of heart failure with preserved ejection fraction (HFpEF). No study has directly evaluated both endothelium-dependent and independent coronary microvascular function in HFpEF. Consecutive patients with HFpEF undergoing invasive coronary physiologic testing and echocardiography were examined. Endothelial function was quantified by the increase in coronary blood flow in response to intracoronary infusion of acetylcholine (10-6 -10-4 mol/L) using a Doppler flow wire with quantitative angiography. Endothelium-independent coronary microvascular function was assessed by the hyperaemic increase in coronary flow reserve in response to adenosine infusion. Among 162 HFpEF patients (67% women), coronary microvascular function was abnormal in 117 (72%). Isolated endothelium-dependent microvascular dysfunction was present in 47 patients (29%), isolated endothelium-independent microvascular dysfunction in 53 patients (33%), and combined microvascular dysfunction in 17 patients (10%). The presence of coronary microvascular dysfunction was not identifiable from medical co-morbidities or other clinical characteristics. As compared to patients with normal endothelium-independent function, HFpEF patients with endothelium-independent coronary microvascular dysfunction displayed lower diastolic relaxation velocities (7.0± 1.8 vs. 8.4± 2.9cm/s, P= 0.002) and higher estimated filling pressures (E/e' 13.1± 4.1 vs. 9.6± 3.4, P< 0.001). There were no relationships between left ventricular structure, function, or haemodynamics and endothelium-dependent coronary vasodilatation. Endothelium-independent microvascular dysfunction was associated with increased mortality. Coronary microvascular dysfunction is common in patients with HFpEF and is caused equally by endothelium-dependent and independent mechanisms, but the presence of microvascular dysfunction cannot be identified from clinical markers and co-morbidities alone. Patients with HFpEF and endothelium-independent microvascular dysfunction display worse diastolic dysfunction and outcomes.

TCT-107 An Attenuated Response to Adenosine Secondary to Coronary Microvascular Dysfunction in Patients Undergoing Fractional Flow Reserve (FFR) Assessment

TCT-107 An Attenuated Response to Adenosine Secondary to Coronary Microvascular Dysfunction in Patients Undergoing Fractional Flow Reserve (FFR) Assessment

Abstract 297: Therapeutic Effects of SK Channel Activator on Cardioprotection in the Setting of Cardioplegic Ischemia-Reperfusion and Cardiopulmonary Bypass

Background: Inactivation of small-conductance calcium-activated potassium (SK) channels contributes to coronary microvascular dysfunction in patients after cardioplegic arrest, cardiopulmonary bypass (CP/CPB) and cardiac surgery. SK-channel activation is cardioprotective in rodent isolated heart model of myocardial infarction and ischemia/reperfusion. In the current study, we investigated the impact of SK activation on myocardial protection in a clinically relevant large animal model of pigs subjected to cardioplegic ischemia/reperfusion and CPB. Methods and Results: Ten Yorkshire pigs were subjected to 1 hour of CP/CPB followed by 1 hour of reperfusion. Pigs received either cold blood hyperkalemic CP alone (CP control) or CP containing the selective SK channel activator NS309 (10 -6 M, n = 5/group). Left ventricular (LV) function was assessed by using pressure-volume loop analysis. Coronary arteriolar relaxation response (in-vitro) to the endothelium-dependent vasodilators adenosine diphosphate (ADP, 10 -9 -10 -4 M) and substance P (10 -12 -10 -7 M) and independent vasodilator sodium nitroprusside (SNP) was evaluated with video-microscopy. Inclusion of NS309 in cold blood CP tends to improve the recovery of LV function compared with the CP controls. CP/CPB and reperfusion significantly reduced endothelium-dependent relaxation response to ADP, 10 -5 M) and substance P (10 -8 M) as compared to control (p&lt;0.05). In contrast, CP-containing NS309 significant improved the recovery of endothelium-dependent relaxation response to ADP and substance P as compared with the control group (p&lt;0.05, respectively). Conclusion: In pig model of CP/CPB, inclusion of the selective SK channel activator in the cold blood cardioplegia improves recovery of coronary arteriolar endothelial function and microvascular relaxation, which may contribute to increased myocardial perfusion and improved LV function.