Coronary microvascular disease: the next frontier for Cardiovascular Research.
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ABSTRACT:
SUBMITTER: Berry C
PROVIDER: S-EPMC7061275 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:Although myocardial ischaemia usually manifests as a consequence of atherosclerosis-dependent obstructive epicardial coronary artery disease, a significant percentage of patients suffer ischaemic events in the absence of epicardial coronary artery obstruction. Experimental and clinical evidence highlight the abnormalities of the coronary microcirculation as a main cause of myocardial ischaemia in patients with 'normal or near normal' coronary arteries on angiography. Coronary microvascular disturbances have been associated with early stages of atherosclerosis even prior to any angiographic evidence of epicardial coronary stenosis, as well as to other cardiac pathologies such as myocardial hypertrophy and heart failure. The main objectives of the manuscript are (i) to provide updated evidence in our current understanding of the pathophysiological consequences of microvascular dysfunction in the heart; (ii) to report on the current knowledge on the relevance of cardiovascular risk factors and comorbid conditions for microcirculatory dysfunction; and (iii) to evidence the relevance of the clinical consequences of microvascular dysfunction. Highlighting the clinical importance of coronary microvascular dysfunction will open the field for research and the development of novel strategies for intervention will encourage early detection of subclinical disease and will help in the stratification of cardiovascular risk in agreement with the new concept of precision medicine.
| S-EPMC7825482 | biostudies-literature
Project description:BACKGROUND:Besides 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. OBJECTIVES:The study sought to investigate the relationship among obesity, CMD, and adverse outcomes. METHODS:Consecutive 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. RESULTS:An 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). CONCLUSIONS:In 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:BackgroundPreliminary semi-quantitative cardiovascular magnetic resonance (CMR) perfusion studies have demonstrated reduced myocardial perfusion reserve (MPR) in patients with angina and risk factors for microvascular disease (MVD), however fully quantitative CMR has not been studied. The purpose of this study is to evaluate whether fully quantitative CMR identifies reduced MPR in this population, and to investigate the relationship between epicardial atherosclerosis, left ventricular hypertrophy (LVH), extracellular volume (ECV), and perfusion.MethodsForty-six patients with typical angina and risk factors for MVD (females, or males with diabetes or metabolic syndrome) who had no obstructive coronary artery disease by coronary angiography and 20 healthy control subjects underwent regadenoson stress CMR perfusion imaging using a dual-sequence quantitative spiral pulse sequence to quantify MPR. Subjects also underwent T1 mapping to quantify ECV, and computed tomographic (CT) coronary calcium scoring to assess atherosclerosis burden.ResultsIn patients with risk factors for MVD, both MPR (2.21 [1.95,2.69] vs. 2.93 [2.763.19], p < 0.001) and stress myocardial perfusion (2.65 ± 0.62 ml/min/g, vs. 3.17 ± 0.49 ml/min/g p < 0.002) were reduced as compared to controls. These differences remained after adjusting for age, left ventricular (LV) mass, body mass index (BMI), and gender. There were no differences in native T1 or ECV between subjects and controls.ConclusionsStress myocardial perfusion and MPR as measured by fully quantitative CMR perfusion imaging are reduced in subjects with risk factors for MVD with no obstructive CAD as compared to healthy controls. Neither myocardial hypertrophy nor fibrosis accounts for these differences.
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Project description:Cancer immunotherapy is a rapidly developing field, but limited in its success by a high tumor burden and immune tolerance. In contrast, immunoprevention has the potential to prevent cancer before the development of immune tolerance, and to prevent cancer recurrence in the setting of minimal residual disease. Although immunoprevention for viral-induced cancers has been successful in the setting of hepatitis B and human papillomavirus vaccination, primary prevention of nonviral-induced cancers is in its infancy. In contrast, prevention of cancer recurrence after adjuvant treatment (secondary prevention) is gaining steam. This review provides an overview of the scope of research in cancer immunoprevention over the last three years and directions for future research.
| S-EPMC4361891 | biostudies-literature
Project description:Ischemic heart disease remains one of the leading causes of death and disability worldwide. However, most patients referred for a noninvasive computed tomography coronary angiogram (CTA) or invasive coronary angiogram for the investigation of angina do not have obstructive coronary artery disease (CAD). Approximately two in five referred patients have coronary microvascular disease (CMD) as a primary diagnosis and, in addition, CMD also associates with CAD and myocardial disease (dual pathology). CMD underpins excess morbidity, impaired quality of life, significant health resource utilization, and adverse cardiovascular events. However, CMD often passes undiagnosed and the onward management of these patients is uncertain and heterogeneous. International standardized diagnostic criteria allow for the accurate diagnosis of CMD, ensuring an often overlooked patient population can be diagnosed and stratified for targeted medical therapy. Key to this is assessing coronary microvascular function-including coronary flow reserve, coronary microvascular resistance, and coronary microvascular spasm. This can be done by invasive methods (intracoronary temperature-pressure wire, intracoronary Doppler flow-pressure wire, intracoronary provocation testing) and non-invasive methods [positron emission tomography (PET), cardiac magnetic resonance imaging (CMR), transthoracic Doppler echocardiography (TTDE), cardiac computed tomography (CT)]. Coronary CTA is insensitive for CMD. Functional coronary angiography represents the combination of CAD imaging and invasive diagnostic procedures.
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Project description:Cardiovascular disease (CVD) is the leading cause of mortality in type 2 diabetes mellitus (T2DM), and modifying cardiovascular risk through lifestyle intervention and pharmacologic therapy is paramount. This review focuses on recent advances in treatment of classical (traditional) cardiovascular risk factors and highlights the impact of novel risk factors, including sleep disorders, socioeconomic status and chronic psychological stress on CVD in T2DM.Obesity is a substantial cardiovascular risk factor, and recently, large trials of lifestyle and surgical (e.g. gastric bypass) interventions impact on CVD in overweight and obese patients have been reported. Lifestyle intervention including low calorie diet and exercise reduced individual cardiovascular risk factors but did not decrease the rate of long-term cardiovascular events. Bariatric surgery was beneficial in reducing cardiovascular risk factors and long-term cardiovascular events. Sleep insufficiency, poor sleep quality and obstructive sleep apnoea lead to higher CVD and further research is needed to characterize the benefit of treating sleep disorders on long-term cardiovascular events in T2DM. Lastly, socioeconomic status and chronic psychological stress independently have a major impact on increasing CVD in T2DM, and public health policies to reduce this burden will be important to address over the coming decade.CVD in T2DM is multifactorial and requires a multifaceted approach in reducing known cardiovascular risks at the individual patient level through lifestyle, pharmacotherapy and surgical interventions and at the societal level through public health policies that support reduction in classical and novel cardiovascular risk factors.
| S-EPMC5704916 | biostudies-other
Project description:Navigation bronchoscopy has reached a new horizon in its evolution. Combining with real-time imaging modalities, such as cone-beam computed tomography (CBCT) and augmented fluoroscopy (AF), navigation success can finally be confirmed with high degree of accuracy in real-time. With utilization of this modality, additional clinical observations are being made to help address the CT-body divergence problem and further improve navigation accuracy. This review focuses on description of CBCT navigation technique, provide tips on addressing CT-Body divergence, and review evidence for CBCT applications in navigation bronchoscopy.
| S-EPMC7330771 | biostudies-literature
Project description:Coronary microvascular dysfunction (CMD) refers to structural and functional abnormalities of the microcirculation that impair myocardial perfusion. CMD plays a pivotal role in numerous cardiovascular diseases, including myocardial ischemia with non-obstructive coronary arteries, heart failure, and acute coronary syndromes. This review summarizes recent advances in CMD pathophysiology, assessment, and treatment strategies, as well as ongoing challenges and future research directions. Signaling pathways implicated in CMD pathogenesis include adenosine monophosphate-activated protein kinase/Krüppel-like factor 2/endothelial nitric oxide synthase (AMPK/KLF2/eNOS), nuclear factor erythroid 2-related factor 2/antioxidant response element (Nrf2/ARE), Angiotensin II (Ang II), endothelin-1 (ET-1), RhoA/Rho kinase, and insulin signaling. Dysregulation of these pathways leads to endothelial dysfunction, the hallmark of CMD. Treatment strategies aim to reduce myocardial oxygen demand, improve microcirculatory function, and restore endothelial homeostasis through mechanisms including vasodilation, anti-inflammation, and antioxidant effects. Traditional Chinese medicine (TCM) compounds exhibit therapeutic potential through multi-targeted actions. Small molecules and regenerative approaches offer precision therapies. However, challenges remain in translating findings to clinical practice and developing effective pharmacotherapies. Integration of engineering with medicine through microfabrication, tissue engineering and AI presents opportunities to advance the diagnosis, prediction, and treatment of CMD.
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