scholarly journals Comprehensive treatment of microvascular angina in overweight women – a randomized controlled pilot trial

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0240722
Author(s):  
Kira Bang Bove ◽  
Malin Nilsson ◽  
Lene Rørholm Pedersen ◽  
Nicolai Mikkelsen ◽  
Hannah Elena Suhrs ◽  
...  
Keyword(s):  
Weight Loss ◽  
Obstructive Coronary Artery Disease ◽  
Pilot Trial ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Coronary Microvascular Dysfunction ◽  
Depression Symptoms ◽  
Comprehensive Treatment ◽  
Microvascular Angina ◽  
Secondary Outcomes

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

Effect of weight loss, exercise and risk factor control in microvascular angina. A randomized controlled pilot trial

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.B Bove ◽  
M Nilsson ◽  
L.R Pedersen ◽  
N Mikkelsen ◽  
H.E Suhrs ◽  
...  
Keyword(s):  
Weight Loss ◽  
Risk Factor ◽  
Microvascular Function ◽  
Anxiety And Depression ◽  
Coronary Microvascular Dysfunction ◽  
Depression Symptoms ◽  
Funding Source ◽  
Risk Factor Control ◽  
Microvascular Angina ◽  
Funding Sources

Abstract Background Coronary microvascular dysfunction (CMD) is a common cause of angina in women and associated with adverse cardiovascular prognosis. Currently, no evidence-based treatment for CMD exists. Purpose To examine whether an intervention targeting cardiovascular risk factors is feasible and improves angina symptoms and microvascular function in women with CMD and no obstructive coronary artery disease. Methods We randomized 62 women aged 40–75, with body mass index &gt;25 kg/m2, angina symptoms monthly or more and coronary flow velocity reserve (CFVR) &lt;2.5 to a 24-week intervention comprising low energy diet, exercise training, and optimized medical treatment of hypertension, dyslipidemia and diabetes or to usual care. Patients were assessed before randomization and after 24 weeks. The primary outcomes were CFVR assessed by transthoracic Doppler stress-echocardiography and angina burden measured by the Seattle Angina Questionnaire (SAQ). Secondary endpoints were exercise capacity (VO2max), body composition and glycemic control, anxiety and depression symptoms measured by the Hospital Anxiety and Depression Scale (HADS). Results Fifty-six participants (90%) completed the study. Median age was 65 years. The intervention group obtained a mean weight loss of 10 kg, mainly (9 kg) from fat tissue (all p&lt;0.0001), increased work load (p&lt;0.01), decreased triglycerides, low density lipoprotein and low plasma cholesterol (all p&lt;0.006). HbA1c in non-diabetes participants also decreased (p&lt;0.05). There was a clinically relevant improvement in all angina symptoms (9–21-point increase on all SAQ scales (all p&lt;0.01)) as well as in depression score (p=0.008). There was no effect on CFVR or other secondary outcomes. Conclusion A major weight loss and intensified risk factor control resulted in significant improvement in angina burden but no improvement of coronary microvascular function among women with microvascular angina. Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Unlimited research funding sources from the Capital region of Denmark and Bispebjerg-Frederiksberg Hospital internal funding sources.

The coronary microcirculation and coronary microvascular dysfunction

2021 ◽  
pp. 18-21
Author(s):  
Romana Herscovici ◽  
C. Noel Bairey Merz
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Obstructive Coronary Artery Disease ◽  
Signs And Symptoms ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Microvascular Angina ◽  
Cardiac Syndrome ◽  
Artery Disease

The role of revascularization in the treatment of obstructive coronary artery disease is well established, and its impact on improving survival has been proven. Nevertheless, patients with signs and symptoms considered of cardiac origin but with no obstructive coronary artery disease on coronary angiography are increasingly seen. Initially described as a ‘paradox’ or cardiac syndrome X and subsequently defined as microvascular angina, angina-like chest pain and evidence of ischaemia with non-obstructive coronary artery disease, is the consequence of altered coronary microvascular response to various stimuli despite non-obstructed epicardial vessels.

scholarly journals Clinical outcomes in patients with primary stable microvascular angina: is the jury still out?

2019 ◽  
Vol 5 (4) ◽  
pp. 283-291 ◽  
Author(s):  
Gaetano Antonio Lanza ◽  
Filippo Crea ◽  
Juan Carlos Kaski
Keyword(s):  
Chest Pain ◽  
Clinical Outcome ◽  
Clinical Outcomes ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Published Data ◽  
Microvascular Angina ◽  
Coronary Events ◽  
Artery Disease

Abstract Several studies have demonstrated that angina chest pain in presence of normal or near normal coronary arteries (NCAs) is mainly related to coronary microvascular dysfunction (CMD). However, controversial findings exist about clinical outcome of these patients. In this article, we critically review characteristics and results of the main clinical studies reporting clinical outcome of stable patients with angina chest pain and non-obstructive coronary artery disease (NO-CAD). Published data indicate that clinical outcomes of these patients are heterogeneous, but those with strict criteria for primary stable microvascular angina (MVA, i.e. typical angina with NCAs mainly related to efforts) do not appear to have an increased mortality or risk of major coronary events. A major determinant of outcome in patients with MVA and NO-CAD seems instead related to non-critical atherosclerotic disease, the presence of which should suggest a more aggressive management of cardiovascular risk factors and preventive management. Future studies should assess whether CMD may have a relevant prognostic role in the latter clinical context and/or in other clinical settings of NO-CAD different from primary stable MVA.

scholarly journals Coronary Microvascular Dysfunction

2020 ◽  
Vol 9 (9) ◽  
pp. 2880
Author(s):  
Federico Vancheri ◽  
Giovanni Longo ◽  
Sergio Vancheri ◽  
Michael Henein
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
Coronary Angiography ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Dysfunction ◽  
Coronary Microcirculation ◽  
Coronary Microvascular Dysfunction ◽  
Microvascular Angina ◽  
Flow Reserve ◽  
Artery Disease

Many patients with chest pain undergoing coronary angiography do not show significant obstructive coronary lesions. A substantial proportion of these patients have abnormalities in the function and structure of coronary microcirculation due to endothelial and smooth muscle cell dysfunction. The coronary microcirculation has a fundamental role in the regulation of coronary blood flow in response to cardiac oxygen requirements. Impairment of this mechanism, defined as coronary microvascular dysfunction (CMD), carries an increased risk of adverse cardiovascular clinical outcomes. Coronary endothelial dysfunction accounts for approximately two-thirds of clinical conditions presenting with symptoms and signs of myocardial ischemia without obstructive coronary disease, termed “ischemia with non-obstructive coronary artery disease” (INOCA) and for a small proportion of “myocardial infarction with non-obstructive coronary artery disease” (MINOCA). More frequently, the clinical presentation of INOCA is microvascular angina due to CMD, while some patients present vasospastic angina due to epicardial spasm, and mixed epicardial and microvascular forms. CMD may be associated with focal and diffuse epicardial coronary atherosclerosis, which may reinforce each other. Both INOCA and MINOCA are more common in females. Clinical classification of CMD includes the association with conditions in which atherosclerosis has limited relevance, with non-obstructive atherosclerosis, and with obstructive atherosclerosis. Several studies already exist which support the evidence that CMD is part of systemic microvascular disease involving multiple organs, such as brain and kidney. Moreover, CMD is strongly associated with the development of heart failure with preserved ejection fraction (HFpEF), diabetes, hypertensive heart disease, and also chronic inflammatory and autoimmune diseases. Since coronary microcirculation is not visible on invasive angiography or computed tomographic coronary angiography (CTCA), the diagnosis of CMD is usually based on functional assessment of microcirculation, which can be performed by both invasive and non-invasive methods, including the assessment of delayed flow of contrast during angiography, measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), evaluation of angina induced by intracoronary acetylcholine infusion, and assessment of myocardial perfusion by positron emission tomography (PET) and magnetic resonance (CMR).

scholarly journals Genetic dysregulation of endothelin-1 is implicated in coronary microvascular dysfunction

2020 ◽  
Vol 41 (34) ◽  
pp. 3239-3252 ◽  
Author(s):  
Thomas J Ford ◽  
David Corcoran ◽  
Sandosh Padmanabhan ◽  
Alisha Aman ◽  
Paul Rocchiccioli ◽  
...  
Keyword(s):  
Allele Frequency ◽  
Ex Vivo ◽  
Obstructive Coronary Artery Disease ◽  
Vascular Diseases ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Microvascular Angina ◽  
Endothelin 1 ◽  
Objective Evidence ◽  
Exercise Treadmill

Abstract Aims Endothelin-1 (ET-1) is a potent vasoconstrictor peptide linked to vascular diseases through a common intronic gene enhancer [(rs9349379-G allele), chromosome 6 (PHACTR1/EDN1)]. We performed a multimodality investigation into the role of ET-1 and this gene variant in the pathogenesis of coronary microvascular dysfunction (CMD) in patients with symptoms and/or signs of ischaemia but no obstructive coronary artery disease (CAD). Methods and results Three hundred and ninety-one patients with angina were enrolled. Of these, 206 (53%) with obstructive CAD were excluded leaving 185 (47%) eligible. One hundred and nine (72%) of 151 subjects who underwent invasive testing had objective evidence of CMD (COVADIS criteria). rs9349379-G allele frequency was greater than in contemporary reference genome bank control subjects [allele frequency 46% (129/280 alleles) vs. 39% (5551/14380); P = 0.013]. The G allele was associated with higher plasma serum ET-1 [least squares mean 1.59 pg/mL vs. 1.28 pg/mL; 95% confidence interval (CI) 0.10–0.53; P = 0.005]. Patients with rs9349379-G allele had over double the odds of CMD [odds ratio (OR) 2.33, 95% CI 1.10–4.96; P = 0.027]. Multimodality non-invasive testing confirmed the G allele was associated with linked impairments in myocardial perfusion on stress cardiac magnetic resonance imaging at 1.5 T (N = 107; GG 56%, AG 43%, AA 31%, P = 0.042) and exercise testing (N = 87; −3.0 units in Duke Exercise Treadmill Score; −5.8 to −0.1; P = 0.045). Endothelin-1 related vascular mechanisms were assessed ex vivo using wire myography with endothelin A receptor (ETA) antagonists including zibotentan. Subjects with rs9349379-G allele had preserved peripheral small vessel reactivity to ET-1 with high affinity of ETA antagonists. Zibotentan reversed ET-1-induced vasoconstriction independently of G allele status. Conclusion We identify a novel genetic risk locus for CMD. These findings implicate ET-1 dysregulation and support the possibility of precision medicine using genetics to target oral ETA antagonist therapy in patients with microvascular angina. Trial registration ClinicalTrials.gov: NCT03193294.

The many faces of myocardial ischaemia and angina

2019 ◽  
Vol 115 (10) ◽  
pp. 1460-1470 ◽  
Author(s):  
Bernard I Levy ◽  
Gerd Heusch ◽  
Paolo G Camici
Keyword(s):  
Blood Flow ◽  
Coronary Arteries ◽  
Myocardial Ischaemia ◽  
Obstructive Coronary Artery Disease ◽  
Coronary Spasm ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Microvascular Angina ◽  
Number Of Patients ◽  
Metabolic Vasodilation

Abstract Obstructive disease of the epicardial coronary arteries is the main cause of angina. However, a number of patients with anginal symptoms have normal coronaries or non-obstructive coronary artery disease (CAD) despite electrocardiographic evidence of ischaemia during stress testing. In addition to limited microvascular vasodilator capacity, the coronary microcirculation of these patients is particularly sensitive to vasoconstrictor stimuli, in a condition known as microvascular angina. This review briefly summarizes the determinants and control of coronary blood flow (CBF) and myocardial perfusion. It subsequently analyses the mechanisms responsible for transient myocardial ischaemia: obstructive CAD, coronary spasm and coronary microvascular dysfunction in the absence of epicardial coronary lesions, and variable combinations of structural anomalies, impaired endothelium-dependent and/or -independent vasodilation, and enhanced perception of pain. Lastly, we exemplify mechanism of angina during tachycardia. Distal to a coronary stenosis, coronary dilator reserve is already recruited and can be nearly exhausted at rest distal to a severe stenosis. Increased heart rate reduces the duration of diastole and thus CBF when metabolic vasodilation is no longer able to increase CBF. The increase in myocardial oxygen consumption and resulting metabolic vasodilation in adjacent myocardium without stenotic coronary arteries further acts to divert blood flow away from the post-stenotic coronary vascular bed through collaterals.

Abstract 9946: Impact of Sex Differences on Invasive Measures of Coronary Microvascular Dysfunction in Patients With Angina in the Absence of Obstructive Coronary Artery Disease

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Yuhei Kobayashi ◽  
Yasuhiro Honda ◽  
William F Fearon ◽  
Shigemitsu Tanaka ◽  
Peter J Fitzgerald ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Sex Differences ◽  
Coronary Artery ◽  
Coronary Flow ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Dysfunction ◽  
Microvascular Function ◽  
Coronary Microvascular Dysfunction ◽  
Flow Reserve ◽  
Artery Disease

Background: Coronary microvascular dysfunction is associated with worse long-term outcomes, especially in women. Coronary flow reserve (CFR) is typically used to interrogate microvascular function; however its variability limits reliability. Alternatively, the index of microcirculatory resistance (IMR) is a direct measure of the microvasculature, but has been less thoroughly studied. We investigated sex differences in CFR and IMR in patients with angina in the absence of obstructive coronary artery disease (CAD). Methods: We prospectively enrolled 117 women and 40 men with angina in the absence of obstructive CAD. We performed CFR, IMR, fractional flow reserve (FFR), and quantitative coronary angiography (QCA) in the left anterior descending artery. Coronary flow was assessed with a thermodilution method by obtaining mean transit time (Tmn: an inverse correlate to absolute flow) at rest and hyperemia. IMR was measured as distal coronary pressure at hyperemia x hyperemic Tmn. Results: All patients had minimal or no atherosclerosis by QCA (%diameter stenosis: 23.2±12.3%), and epicardial disease was milder in women (FFR: 0.88±0.04 vs. 0.87±0.04, p=0.04). IMR was similar between the sexes (20.7±9.8 vs. 19.1±8.0, p=0.45), but CFR was lower in women (3.8±1.6 vs. 4.8±1.9, p=0.004). This was primarily due to a shorter resting Tmn in women (p=0.005), while hyperemic Tmn was identical (p=0.79) (Figure). The shorter resting Tmn in women, reflecting increased resting coronary flow, accounted for the lower CFR. In multivariate analysis, female sex was an independent predictor of lower CFR and shorter resting Tmn, but not a predictor of IMR or hyperemic Tmn. Conclusions: Despite women and men having similar microvascular function by IMR, CFR is lower in women. This discrepancy appears to be due to differences in resting coronary flow between the sexes. The impact of sex differences should be considered in interpretation of physiologic indices using resting coronary flow.

scholarly journals Treatment of coronary microvascular dysfunction

2020 ◽  
Vol 116 (4) ◽  
pp. 856-870 ◽  
Author(s):  
C Noel Bairey Merz ◽  
Carl J Pepine ◽  
Hiroki Shimokawa ◽  
Colin Berry
Keyword(s):  
Enzyme Inhibitor ◽  
Obstructive Coronary Artery Disease ◽  
Microvascular Dysfunction ◽  
Small Sample ◽  
Adverse Outcomes ◽  
Functional Improvement ◽  
Coronary Microvascular Dysfunction ◽  
Female Population ◽  
Microvascular Angina ◽  
Flow Reserve

Abstract Contemporary data indicate that patients with signs and symptoms of ischaemia and non-obstructive coronary artery disease (INOCA) often have coronary microvascular dysfunction (CMD) with elevated risk for adverse outcomes. Coronary endothelial (constriction with acetylcholine) and/or microvascular (limited coronary flow reserve with adenosine) dysfunction are well-documented, and extensive non-obstructive atherosclerosis is often present. Despite these data, patients with INOCA currently remain under-treated, in part, because existing management guidelines do not address this large, mostly female population due to the absence of evidence-based data. Relatively small sample-sized, short-term pilot studies of symptomatic mostly women, with INOCA, using intense medical therapies targeting endothelial, microvascular, and/or atherosclerosis mechanisms suggest symptom, ischaemia, and coronary vascular functional improvement, however, randomized, controlled outcome trials testing treatment strategies have not been completed. We review evidence regarding CMD pharmacotherapy. Potent statins in combination with angiotensin-converting enzyme inhibitor (ACE-I) or receptor blockers if intolerant, at maximally tolerated doses appear to improve angina, stress testing, myocardial perfusion, coronary endothelial function, and microvascular function. The Coronary Microvascular Angina trial supports invasive diagnostic testing with stratified therapy as an approach to improve symptoms and quality of life. The WARRIOR trial is testing intense medical therapy of high-intensity statin, maximally tolerated ACE-I plus aspirin on longer-term outcomes to provide evidence for guidelines. Novel treatments and those under development appear promising as the basis for future trial planning.

scholarly journals Epicardial adipose tissue differentiates in patients with and without coronary microvascular dysfunction

2021 ◽  
Author(s):  
Ihab Mahmoud ◽  
Iryna Dykun ◽  
Luisa Kärner ◽  
Stefanie Hendricks ◽  
Matthias Totzeck ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Regression Analysis ◽  
Epicardial Adipose Tissue ◽  
Obstructive Coronary Artery Disease ◽  
Age Groups ◽  
Microvascular Dysfunction ◽  
Coronary Microvascular Dysfunction ◽  
Local Inflammation ◽  
And Gender ◽  
Fat Depot

Abstract Background/Objectives Coronary microvascular dysfunction (CMD) is a common disorder, leading to symptoms similar to obstructive coronary artery disease and bears important prognostic implications. Local inflammation is suggested to promote development of CMD. Epicardial adipose tissue (EAT) is a local visceral fat depot surrounding the heart and the coronary arteries, modifying the inflammatory environment of the heart. We compared EAT in patients with and without CMD. Methods We retrospectively included consecutive patients undergoing diagnostic coronary angiography as well as transthoracic echocardiography between March and October 2016. EAT thickness was defined as space between the epicardial wall of the myocardium and the visceral layer of the pericardium and EAT index was calculated as EAT thickness/body surface area. Logistic regression analysis was used to determine the association of EAT index with the presence of CMD. Results Overall, 399 patients (mean age 60.2 ± 14.0 years, 46% male) were included. EAT thickness was significantly higher in patients with CMD compared to patients without CMD (EAT thickness 4.4 ± 1.8 vs. 4.9 ± 2.4 mm, p = 0,048 for patients without and with CMD, respectively). In univariate regression analysis, EAT index was associated with a 30% higher frequency of CMD (odds ratio [95% confidence interval]: 1.30 [1.001–1.69], p = 0.049). Effect sizes remained stable upon adjustment for body mass index (BMI, 1.30 [1.003–1.70], p = 0.048), but were attenuated when ancillary adjusting for age and gender (1.17 [0.90–1.54, p = 0.25). The effect was more pronounced in patients >65 years of age and independent of BMI and sex (1.85 [1.14–3.00], p = 0.013). Conclusion EAT thickness is independently associated with CMD and can differentiate between patients with and without CMD especially in older age groups. Our results support the hypothesis that modulation of local inflammation by epicardial fat is involved in the development of CMD.

Sign in / Sign up

Export Citation Format

Share Document