Coronary microvascular dysfunction: an update.
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SUBMITTER: Crea F
PROVIDER: S-EPMC4006091 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description: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.
| S-EPMC7061279 | biostudies-literature
Project description:Coronary microvascular dysfunction (CMD) is commonly present in patients with metabolic derangements and is increasingly recognized as an important contributor to myocardial ischaemia, both in the presence and absence of epicardial coronary atherosclerosis. The latter condition is termed 'ischaemia and no obstructive coronary artery disease' (INOCA). Notwithstanding the high prevalence of INOCA, effective treatment remains elusive. Although to date there is no animal model for INOCA, animal models of CMD, one of the hallmarks of INOCA, offer excellent test models for enhancing our understanding of the pathophysiology of CMD and for investigating novel therapies. This article presents an overview of currently available experimental models of CMD-with an emphasis on metabolic derangements as risk factors-in dogs, swine, rabbits, rats, and mice. In all available animal models, metabolic derangements are most often induced by a high-fat diet (HFD) and/or diabetes mellitus via injection of alloxan or streptozotocin, but there is also a wide variety of spontaneous as well as transgenic animal models which develop metabolic derangements. Depending on the number, severity, and duration of exposure to risk factors-all these animal models show perturbations in coronary microvascular (endothelial) function and structure, similar to what has been observed in patients with INOCA and comorbid conditions. The use of these animal models will be instrumental in identifying novel therapeutic targets and for the subsequent development and testing of novel therapeutic interventions to combat ischaemic heart disease, the number one cause of death worldwide.
| S-EPMC7061277 | biostudies-literature
Project description:40-70% of patients undergoing invasive coronary angiography with signs and symptoms of ischemia are found to have no obstructive coronary artery disease (INOCA). When this heterogeneous group undergo coronary function testing, approximately two-thirds have demonstrable coronary microvascular dysfunction (CMD), which is independently associated with adverse prognosis. There are four distinct phenotypes, or subgroups, each with unique pathophysiological mechanisms and responses to therapies. The clinical phenotypes are microvascular angina, vasospastic angina, mixed (microvascular and vasospastic), and non-cardiac symptoms (reclassification as non-INOCA). The Coronary Vasomotor Disorders International Study Group (COVADIS) have proposed standardized criteria for diagnosis. There is growing awareness of these conditions among clinicians and within guidelines. Testing for CMD can be done using invasive or non-invasive modalities. The CorMicA study advocates the concept of 'functional angiography' to guide stratified medical therapy. Therapies broadly fall into two categories: those that modulate cardiovascular risk and those to alleviate angina. Management should be tailored to the individual, with periodic reassessment for efficacy. Phenotype-based management is a worthy endeavor for both patients and clinicians, aligning with the concept of 'precision medicine' to improve prognosis, symptom burden, and quality of life. Here, we present a contemporary approach to the phenotype-based management of patients with INOCA.
| S-EPMC9834338 | biostudies-literature
Project description:Coronary microvascular dysfunction (CMD) refers to a subset of structural and/or functional disorders of coronary microcirculation that lead to impaired coronary blood flow and eventually myocardial ischemia. Amid the growing knowledge of the pathophysiological mechanisms and the development of advanced tools for assessment, CMD has emerged as a prevalent cause of a broad spectrum of cardiovascular diseases (CVDs), including obstructive and nonobstructive coronary artery disease, diabetic cardiomyopathy, and heart failure with preserved ejection fraction. Of note, the endothelium exerts vital functions in regulating coronary microvascular and cardiac function. Importantly, insufficient or uncontrolled activation of endothelial autophagy facilitates the pathogenesis of CMD in diverse CVDs. Here, we review the progress in understanding the pathophysiological mechanisms of autophagy in coronary endothelial cells and discuss their potential role in CMD and CVDs.
| S-EPMC9265562 | biostudies-literature
Project description:BackgroundBesides body mass index (BMI), other discriminators of cardiovascular risk are needed in obese patients, who may or may not undergo consideration for bariatric surgery. Coronary microvascular dysfunction (CMD), defined as impaired coronary flow reserve (CFR) in the absence of flow-limiting coronary artery disease, identifies patients at risk for adverse events independently of traditional risk factors.ObjectivesThe study sought to investigate the relationship among obesity, CMD, and adverse outcomes.MethodsConsecutive patients undergoing evaluation for coronary artery disease with cardiac stress positron emission tomography demonstrating normal perfusion (N = 827) were followed for median 5.6 years for events, including death and hospitalization for myocardial infarction or heart failure.ResultsAn inverted independent J-shaped relationship was observed between BMI and CFR, such that in obese patients CFR decreased linearly with increasing BMI (adjusted p < 0.0001). In adjusted analyses, CFR but not BMI remained independently associated with events (for a 1-U decrease in CFR, adjusted hazard ratio: 1.95; 95% confidence interval: 1.41 to 2.69; p < 0.001; for a 10-U increase in BMI, adjusted hazard ratio: 1.20; 95% confidence interval: 0.95 to 1.50; p = 0.125) and improved model discrimination (C-index 0.71 to 0.74). In obese patients, individuals with impaired CFR demonstrated a higher adjusted rate of events (5.7% vs. 2.6%; p = 0.002), even in those not currently meeting indications for bariatric surgery (6.4% vs. 2.6%; p = 0.04).ConclusionsIn patients referred for testing, CMD was independently associated with elevated BMI and adverse outcomes, and was a better discriminator of risk than BMI and traditional risk factors. CFR may facilitate management of obese patients beyond currently used markers of risk.
| S-EPMC6592712 | biostudies-literature
Project description:BackgroundTianxiangdan (TXD) is used in traditional Chinese medicine because of its therapeutic and preventive effects in the treatment of coronary heart disease. However, the underlying mechanism of TXD in coronary microvascular disease (CMD) remains unclear.MethodsA rat model of CMD was developed to study the mechanism of TXD activity. Sodium laurate was injected into the left ventricle of Sprague-Dawley rats to induce CMD. The rats were divided into six groups: a sham-operated (sham) group, an untreated CMD group, a low-dose TXD group (0.81 g·kg-1·d-1), a mid-dose TXD (TXD-M) group (1.62 g·kg-1·d-1), a high-dose TXD (TXD-H) group (3.24 g·kg-1·d-1), and a nicorandil (NCR) group (1.35 mg·kg-1·d-1). The effect of TXD on rats with CMD was observed after four weeks, and the mechanism of TXD in lipopolysaccharide (LPS)-induced cardiac microvascular endothelial cells (CMECs) was explored through treatment with 50 μg/mL TXD.ResultsCompared with the rats in the untreated CMD group, rats in the TXD-M and TXD-H groups showed higher left ventricular ejection fraction values, improved pathological structures, decreased expressions of interleukin (IL)-1β, tumor necrosis factor-alpha (TNF-α), phosphorylated nuclear factor-κB inhibitor α (IκBα) and phosphorylated p65, and increased expressions of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (P < 0.05). These effects were more pronounced in the TXD-H group than in the TXD-M group. In vitro experiments showed that TXD treatment increased the viability of LPS-induced CMECs and decreased the expression of IL-1β, TNF-α, phosphorylated IκBα, and phosphorylated p65 (P < 0.05). However, the effects of TXD on CMECs were markedly reversed upon treatment with ML385 (Nrf2 inhibitor).ConclusionThe results showed that TXD exerts a protective effect on rats with CMD and related inflammatory injuries, and its anti-inflammatory mechanism is related to the activation of Nrf2 signalling.
| S-EPMC8660204 | biostudies-literature
Project description:Background In the absence of obstructive coronary stenoses, abnormality of noninvasive stress tests (NIT) in patients with chronic coronary syndromes may indicate myocardial ischemia of nonobstructive coronary arteries (INOCA). The differential prognosis of INOCA according to the presence of coronary microvascular dysfunction (CMD) and incremental prognostic value of CMD with intracoronary physiologic assessment on top of NIT information remains unknown. Methods and Results From the international multicenter registry of intracoronary physiologic assessment (ILIAS [Inclusive Invasive Physiological Assessment in Angina Syndromes] registry, N=2322), stable patients with NIT and nonobstructive coronary stenoses with fractional flow reserve >0.80 were selected. INOCA was diagnosed when patients showed positive NIT results. CMD was defined as coronary flow reserve ≤2.5. According to the presence of INOCA and CMD, patients were classified into 4 groups: group 1 (no INOCA nor CMD, n=116); group 2 (only CMD, n=90); group 3 (only INOCA, n=41); and group 4 (both INOCA and CMD, n=40). The primary outcome was major adverse cardiovascular events, a composite of all-cause death, target vessel myocardial infarction, or clinically driven target vessel revascularization at 5 years. Among 287 patients with nonobstructive coronary stenoses (fractional flow reserve=0.91±0.06), 81 patients (38.2%) were diagnosed with INOCA based on positive NIT. By intracoronary physiologic assessment, 130 patients (45.3%) had CMD. Regardless of the presence of INOCA, patients with CMD showed a significantly lower coronary flow reserve and higher hyperemic microvascular resistance compared with patients without CMD (P<0.001 for all). The cumulative incidence of major adverse cardiovascular events at 5 years were 7.4%, 21.3%, 7.7%, and 34.4% in groups 1 to 4. By documenting CMD (groups 2 and 4), intracoronary physiologic assessment identified patients at a significantly higher risk of major adverse cardiovascular events at 5 years compared with group 1 (group 2: adjusted hazard ratio [HRadjusted], 2.88; 95% CI, 1.52-7.19; P=0.024; group 4: HRadjusted, 4.00; 95% CI, 1.41-11.35; P=0.009). Conclusions In stable patients with nonobstructive coronary stenoses, a diagnosis of INOCA based only on abnormal NIT did not identify patients with higher risk of long-term cardiovascular events. Incorporating intracoronary physiologic assessment to NIT information in patients with nonobstructive disease allowed identification of patient subgroups with up to 4-fold difference in long-term cardiovascular events. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT04485234.
| S-EPMC9238617 | biostudies-literature
Project description:Coronary microvascular dysfunction (CMD) is a prevalent and prognostically important finding in patients with symptoms suggestive of coronary artery disease. The relative extent to which CMD affects both sexes is largely unknown.We investigated 405 men and 813 women who were referred for evaluation of suspected coronary artery disease with no previous history of coronary artery disease and no visual evidence of coronary artery disease on rest/stress positron emission tomography myocardial perfusion imaging. Coronary flow reserve was quantified, and coronary flow reserve <2.0 was used to define the presence of CMD. Major adverse cardiac events, including cardiac death, nonfatal myocardial infarction, late revascularization, and hospitalization for heart failure, were assessed in a blinded fashion over a median follow-up of 1.3 years (interquartile range, 0.5-2.3 years). CMD was highly prevalent both in men and women (51% and 54%, respectively; Fisher exact test =0.39; equivalence P=0.0002). Regardless of sex, coronary flow reserve was a powerful incremental predictor of major adverse cardiac events (hazard ratio, 0.80 [95% confidence interval, 0.75-086] per 10% increase in coronary flow reserve; P<0.0001) and resulted in favorable net reclassification improvement (0.280 [95% confidence interval, 0.049-0.512]), after adjustment for clinical risk and ventricular function. In a subgroup (n=404; 307 women/97 men) without evidence of coronary artery calcification on gated computed tomography imaging, CMD was common in both sexes, despite normal stress perfusion imaging and no coronary artery calcification (44% of men versus 48% of women; Fisher exact test P=0.56; equivalence P=0.041).CMD is highly prevalent among at-risk individuals and is associated with adverse outcomes regardless of sex. The high prevalence of CMD in both sexes suggests that it may be a useful target for future therapeutic interventions.
| S-EPMC4076200 | biostudies-literature
Project description:The patient, a 68-year-old man, presented to our emergency room with chest pain, prompting an emergency cardiac catheterization due to elevated cardiac troponin-I levels. While no obvious coronary artery stenosis was found, there was evidence of apical ballooning wall motion in the left ventricle, leading to a diagnosis of takotsubo syndrome. Three months later, he occasionally experienced chest pain at rest, prompting us to conduct another cardiac catheterization. Left ventriculography showed normal contraction. Suddenly, he experienced chest pain accompanied by ST elevation, which occurred spontaneously. Subsequently, slow-flow phenomenon was observed in the intermediate part of left anterior descending artery (LAD). We promptly administered nitroglycerin to alleviate the symptoms. Following the diagnosis of coronary microvascular dysfunction (CMD), he started calcium-channel blocker therapy and remained asymptomatic. One year later, we re-performed cardiac catheterization to further explore his condition. Acetylcholine provocation test was performed, which showed no epicardial coronary spasm. However, lactic acid elevation was observed in the coronary sinus blood sample. Additionally, a coronary physiological measurement in the LAD revealed a high index of microcirculatory resistance and low coronary flow reserve. Based on this series of clinical events, we inferred a significant contribution of CMD to the patient's condition.Learning objectiveCoronary microvascular dysfunction (CMD) is increasingly recognized as an important cardiovascular disease, leading to myocardial ischemia, which is occasionally associated with takotsubo syndrome (TTS). In this report, we present a case of spontaneous CMD associated with TTS. This case emphasizes the significance of accurate diagnosis and appropriate treatment, highlighting the importance of recognizing CMD in patients with TTS.
| S-EPMC10927452 | biostudies-literature
Project description:BackgroundCoronary microvascular dysfunction (CMD) is associated with heart failure with preserved ejection fraction (HFpEF); however, pathophysiology is not well described.HypothesisWe hypothesized that CMD in women with suspected ischemia with no obstructive coronary artery disease (INOCA) is associated with cardiomyocyte dysfunction reflected by plasma levels of a cardiomyocyte calcium handling protein, cardiac bridge integrator 1 (cBIN1).MethodsWomen with suspected INOCA undergoing coronary function testing were included. Coronary flow reserve, vasodilation to nitroglycerin, change in coronary blood flow (ΔCBF), and vasodilation to acetylcholine (ΔAch) were evaluated. cBIN1 score (CS) levels in these women (n = 39) were compared to women with HFpEF (n = 20), heart failure with reduced ejection fraction (HFrEF) (n = 36), and reference controls (RC) (n = 50). Higher CS indicates cardiomyocyte tubule dysfunction.ResultsINOCA, HFpEF, and HFrEF women were older than RC (p < .05). Higher CS was associated with vasoconstriction to acetylcholine (r = -0.43, p = .011) with a trend towards lower ΔCBF (r = 0.30, p = .086). Higher CS was specific for ΔAch and ΔCBF but had limited sensitivity. INOCA women had higher CS than RC, but lower CS than HFpEF/HFrEF groups (p < .001).ConclusionsCS, a plasma biomarker indicating poor cardiomyocyte health, was higher in women with suspected INOCA as compared to RC, but lower than in women with HFpEF. Elevated CS in suspected INOCA patients represents an intermediate group between health and disease, supporting the hypothesis that CMD may progress to HFpEF. Larger prospective cohort studies are needed to confirm the pathophysiological relationship between cBIN1, CMD, and HFpEF.
| S-EPMC8571552 | biostudies-literature