scholarly journals Adenosine vs Regadenoson Pharmacologic Stress Differs in Women with Suspected Coronary Microvascular Dysfunction: A Report from the Women’s Ischemia Syndrome Evaluation-Coronary Vascular Dysfunction (WISE-CVD) Study

2019 ◽  
pp. 1-7
Author(s):  
C. Noel Bairey Merz ◽  
Puja K. Mehta ◽  
André Rogatko ◽  
Behzad Sharif ◽  
C. Noel Bairey Merz ◽  
...  

Background: Stress cardiac magnetic resonance (CMR) imaging with myocardial perfusion reserve index (MPRI) measurement has emerged as a noninvasive method for assessing coronary microvascular dysfunction (CMD) in the absence of obstructive coronary artery disease (CAD). Pharmacologic stress with adenosine or regadenoson is typically used with comparable coronary vasodilation, but higher unadjusted MPRI has been reported with regadenoson in healthy men. This difference has not been assessed in symptomatic or healthy women. Methods: In a prospective cohort study, 139 symptomatic women with suspected CMD and no obstructive CAD underwent stress CMR and invasive coronary flow reserve (CFR) testing. Adenosine was the default vasodilator (n=99), while regadenoson was used if history of asthma or prior adenosine intolerance (n=40). Stress CMR was also performed in 40 age-matched healthy controls using adenosine (n=20) and regadenoson (n=20). Unpaired t-tests and analysis of covariance were performed to compare MPRI with adenosine and regadenoson in the symptomatic women and healthy controls. Results: Compared to regadenoson cases, adenosine cases had lower invasive CFR (2.64±0.62 vs 2.94±0.68, p=0.01) and pharmacologic heart rate change (28±16 vs 38±15 bpm, p=0.0008). Unadjusted MPRI was lower in the adenosine compared to regadenoson cases (1.73±0.38 vs 2.27±0.59, p<0.0001). When adjusted for heart rate, rate-pressure-product, and invasive CFR, MPRI remained lower in the adenosine cases (p<0.0001). Invasive CFR to adenosine correlated with adenosine MPRI (r 0.17, p=0.02) but not regadenoson MPRI (r -0.14, p=0.19). There was no significant difference in MPRI in the controls who received adenosine vs regadenoson (2.27±0.33 vs 2.38±0.44, p=0.36). Conclusion: In women undergoing stress CMR for suspected CMD, those who received adenosine had lower MPRI than those who received regadenoson. However, there were no differences in MPRI in the healthy controls. These findings suggest there may be physiologic differences in adenosine and regadenoson response in the coronary microcirculation of symptomatic women.

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Ali Ahmad ◽  
Jaskanwal D Sara ◽  
Michel T Corban ◽  
Takumi Toya ◽  
Ilke Ozcan ◽  
...  

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 (<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<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 <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


2018 ◽  
Vol 24 (25) ◽  
pp. 2960-2966
Author(s):  
Zorana Vasiljevic ◽  
Gordana Krljanac ◽  
Marija Zdravkovic ◽  
Ratko Lasica ◽  
Danijela Trifunovic ◽  
...  

Background: The Heart Failure with Preserved Ejection Fraction (HFpEF) is defined as the preserved left ventricular ejection fraction (LVEF) with the signs of heart failure, elevated natriuretic peptides, and either the evidence of the structural heart disease or diastolic dysfunction. The importance of this form of heart failure was increased after studies where the mortality rates and readmission to the hospital were founded similar as in patients with HF and reduced EF (HFrEF). Coronary microvascular ischemia, cardiomyocyte injury and stiffness could be important factors in the pathophysiology of HFpEF. Methods: The goal of this work is to analyse the relationship of HFpEF and coronary microcirculation in previous studies. Results: The useful diagnostic marker of coronary microcirculation in HFpEF may be the parameters measured by transthoracic echocardiography (TTE), the coronary flow reserve (CFR), as well as fractional flow reserve (FFR) and quantitative myocardial contrast echocardiography (MCE). Cardiac magnetic resonance (CMR) imaging represents the diagnostic gold standard in HFpEF. Coronary microvascular dysfunction in the absence of obstructive coronary artery disease (CAD) is poorly understood and may be more prevalent amongst women than men. Troponin level may be important in risk stratification of HEpEF patients. Conclusion: There are no precise answers with respect to the pathophysiological mechanism, nor are there any precise practical clinical assessment of and diagnostic method for coronary microvascular dysfunction and diastolic dysfunction. In accordance with that, there is no well-established treatment for HFpEF.


2018 ◽  
Vol 39 (37) ◽  
pp. 3439-3450 ◽  
Author(s):  
Sanjiv J Shah ◽  
Carolyn S P Lam ◽  
Sara Svedlund ◽  
Antti Saraste ◽  
Camilla Hage ◽  
...  

Abstract Aims To date, clinical evidence of microvascular dysfunction in patients with heart failure (HF) with preserved ejection fraction (HFpEF) has been limited. We aimed to investigate the prevalence of coronary microvascular dysfunction (CMD) and its association with systemic endothelial dysfunction, HF severity, and myocardial dysfunction in a well defined, multi-centre HFpEF population. Methods and results This prospective multinational multi-centre observational study enrolled patients fulfilling strict criteria for HFpEF according to current guidelines. Those with known unrevascularized macrovascular coronary artery disease (CAD) were excluded. Coronary flow reserve (CFR) was measured with adenosine stress transthoracic Doppler echocardiography. Systemic endothelial function [reactive hyperaemia index (RHI)] was measured by peripheral arterial tonometry. Among 202 patients with HFpEF, 151 [75% (95% confidence interval 69–81%)] had CMD (defined as CFR <2.5). Patients with CMD had a higher prevalence of current or prior smoking (70% vs. 43%; P = 0.0006) and atrial fibrillation (58% vs. 25%; P = 0.004) compared with those without CMD. Worse CFR was associated with higher urinary albumin-to-creatinine ratio (UACR) and NTproBNP, and lower RHI, tricuspid annular plane systolic excursion, and right ventricular (RV) free wall strain after adjustment for age, sex, body mass index, atrial fibrillation, diabetes, revascularized CAD, smoking, left ventricular mass, and study site (P < 0.05 for all associations). Conclusions PROMIS-HFpEF is the first prospective multi-centre, multinational study to demonstrate a high prevalence of CMD in HFpEF in the absence of unrevascularized macrovascular CAD, and to show its association with systemic endothelial dysfunction (RHI, UACR) as well as markers of HF severity (NTproBNP and RV dysfunction). Microvascular dysfunction may be a promising therapeutic target in HFpEF.


2010 ◽  
Vol 55 (10) ◽  
pp. A167.E1564
Author(s):  
Elena Osto ◽  
Stefano Piaserico ◽  
Anna Maddalozzo ◽  
Giulia Forchetti ◽  
Roberta Montisci ◽  
...  

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Yun-Ting Wang ◽  
Wei Zhao ◽  
Ashton A Huckaby ◽  
Xiang Li ◽  
Yang Zhang

Accumulating evidence indicates coronary microvascular dysfunction (CMD) contributes to myocardial ischemia with or without epicardial coronary atherosclerosis. However, it remains unknown which molecular pathway is associated with compromised coronary microvascular function preceding the development of myocardial ischemic injury. Recent studies suggest that autophagy-lysosomal signaling pathway is involved in the regulation of endothelial homeostasis under various metabolic stresses such as hypercholesterolemia. In this study, the early effects of hypercholesterolemia on the function and integrity of coronary microcirculation were studied in mice and the expressions of various molecular markers of autophagy-lysosome pathway were also determined in the coronary circulation. Mice were fed a hypercholesterolemic paigen diet (PD) for 8 weeks and coronary microvascular function was determined by measuring coronary flow reserve (CFR) under baseline and hyperemic conditions. The effects of PD on cardiac function or remodeling were also assessed by echocardiograph or immunohistochemistry studies. In PD-fed hypercholesterolemic mice, hyperemia-induced increase in CFR was significantly abrogated compared to that in normal chow diet-fed (ND) control mice (PD: 1.583±0.4193 vs. ND: 3.087±0.586) (n=7-8). The diet-induced hypercholesterolemia did not lead to cardiac dysfunction (EF%, PD: 59.870±7.549 vs ND: 64.040±9.088) or hypertrophic remodeling (LV mass (mg), PD: 92.240±14.410 vs ND: 96.030±25.07). PD increased mild cardiac inflammation and fibrosis but did not resulted in rarefaction in the myocardium. In small coronary arterial wall, PD induced endothelial inflammasome activation and inflammation, which was accompanied by upregulation of autophagy and lysosome signaling pathway. In conclusion, hypercholesterolemic diet induces CMD without alterations in cardiac function or remodeling. These alterations in coronary microvascular function represent the early effects of diet-induced hypercholesterolemia, which may be ameliorated with activation of autophagy and lysosome signaling pathways.


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
R. David Anderson ◽  
John W. Petersen ◽  
Puja K. Mehta ◽  
Janet Wei ◽  
B. Delia Johnson ◽  
...  

Objective. In a separate, contemporary cohort, we sought to confirm findings of the original Women’s Ischemia Syndrome Evaluation (WISE). Background. The original WISE observed a high prevalence of both invasively determined coronary endothelial and coronary microvascular dysfunction (CMD) that predicted adverse events in follow-up. Methods. We comparatively studied the WISE-Coronary Vascular Dysfunction (CVD) cohort (2009-2011), with signs and symptoms of ischemia but without significant CAD, to the original WISE (1997-2001) cohort. CMD was defined as coronary flow reserve (CFR) ≤2.5, or endothelial dysfunction as epicardial coronary artery constriction to acetylcholine (ACH), or <20% epicardial coronary dilation to nitroglycerin (NTG). Results. In WISE (n=181) and WISE-CVD (n=235) women, mean age in both was 54 years, and 83% were white (WISE) vs 74% (WISE-CVD, p=0.04). Use of hormone replacement therapy was less frequent in WISE-CVD vs WISE (46% vs 57%, p=0.026) as was presence of hypertension (40% vs 52%, p=0.013), hyperlipidemia (20% vs 46%, p<0.0001), and smoking (46% vs 56%, p=0.036). Similar rates were observed in WISE-CVD and WISE cohorts for CMD (mean CFR 2.7±0.6 vs 2.6±0.8, p=0.35), mean change in diameter with intracoronary ACH (0.2±10.0 vs 1.6±12.8 mm, p=0.34), and mean change in diameter with intracoronary NTG (9.7±13.0 vs 9.8±13.5 mm, p=0.94), respectively. Conclusions. This study confirms prevalence of CMD in the contemporary WISE-CVD cohort similar to that of the original WISE cohort, despite a lower risk factor burden in WISE-CVD. Because these coronary functional abnormalities predict major adverse cardiac events, clinical trials of therapies targeting these abnormalities are indicated.


Author(s):  
Haseeb Rahman ◽  
Ozan M. Demir ◽  
Matthew Ryan ◽  
Hannah McConkey ◽  
Cian Scannell ◽  
...  

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


2019 ◽  
Vol 27 (12) ◽  
pp. 621-628
Author(s):  
D. A. J. P. van de Sande ◽  
P. C. Barneveld ◽  
J. Hoogsteen ◽  
P. A. Doevendans ◽  
H. M. C. Kemps

Abstract Aims In asymptomatic athletes, abnormal exercise test (ET) results have a poor positive predictive value. It is unknown whether abnormal ET results in the absence of obstructive coronary artery disease (CAD) are related to coronary microvascular dysfunction. It is also unknown whether they should be considered false-positive ET results or a consequence of physiological adaptation to sport. In our study, we evaluated whether athletes with abnormal ET results and documented myocardial ischaemia in the absence of obstructive CAD have an attenuated microvascular function and whether coronary microvascular dysfunction is related to endothelial dysfunction. Methods and results Nine athletes with concordant abnormal ET and myocardial perfusion scintigraphy (MPS) results without obstructive CAD were compared with age- and gender-matched individuals with a low-to-intermediate a priori risk of CAD. Coronary flow reserve was assessed by Rubidium-82 positron emission tomography (PET) imaging. Endothelin‑1 concentrations were measured to evaluate endothelial function. Coronary flow reserve was significantly lower in athletes (3.3 ± 0.8 versus 4.2 ± 0.6, p = 0.014 respectively). Endothelin‑1 levels were significantly higher in athletes (1.3 ± 0.2 pg/ml versus 1.0 ± 0.2 pg/ml, p = 0.012 respectively). There was no correlation between endothelin‑1 concentrations and mean global coronary flow reserve (r = 0.12). Conclusion Athletes with abnormal ET and MPS outcomes indicative for myocardial ischaemia and no obstructive CAD have a lower coronary flow reserve compared with non-athletes with low-to-intermediate a priori risk of CAD, suggesting an attenuated coronary microvascular function. Higher endothelin‑1 concentrations in athletes suggest that endothelial-dependent dysfunction is an important determinant of the attenuated microvascular function.


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