In recent years, it has become apparent that coronary microvascular dysfunction plays a pivotal pathogenic role in angina pectoris. Functional and structural mechanisms can affect the physiological ...function of the coronary microvasculature and lead to myocardial ischemia in people without coronary atheromatous disease and also in individuals with obstructive coronary artery disease. Abnormal dilatory responses of the coronary microvessels, coronary microvascular spasm, and extravascular compressive forces have been identified as pathogenic mechanisms in both chronic and acute forms of ischemic heart disease. The condition characterized by anginal symptoms and evidence of myocardial ischemia triggered by coronary microvascular dysfunction, in the absence of obstructive coronary disease, is known as microvascular angina. The concept of microvascular angina, however, may extend further to include patients with obstructive coronary artery disease and individuals with angina after coronary revascularization or heart transplantation because coronary microvascular dysfunction contributes to myocardial ischemia in many such patients. Patients with microvascular angina constitute a sizeable proportion of all cases of stable angina undergoing diagnostic coronary angiography and of those with persisting angina after successful coronary revascularization. Coronary microvascular dysfunction is also often responsible for angina in individuals with cardiomyopathy and heart valve disease as well as acute coronary syndrome cases such as Takotsubo syndrome and myocardial infarction with no obstructive coronary artery disease. Patients with stable microvascular angina present typically with effort or rest chest pain and a reduced coronary flow reserve or microvascular spasm. This condition, which affects women and men, can markedly impair quality of life and prognosis and represents a substantial cost burden to healthcare systems and individuals alike. In recent years, progress in the diagnosis of myocardial ischemia and the use of tests to investigate functional and structural causes for a reduced coronary flow reserve and microvascular spasm have allowed the identification of an increased number of cases of microvascular angina in everyday clinical practice. Although some of the available anti-anginal drugs may be helpful, treatment of coronary microvascular dysfunction remains a major challenge. The present article discusses the fundamental role that coronary microvascular dysfunction plays in the pathogenesis of ischemic heart disease, the clinical characteristics of patients presenting with microvascular angina, and possible diagnostic and therapeutic strategies.
Originally described by Japanese authors in the 1990s, Takotsubo syndrome (TTS) generally presents as an acute myocardial infarction characterized by severe left ventricular dysfunction. TTS, ...however, differs from an acute coronary syndrome because patients have generally a normal coronary angiogram and left ventricular dysfunction, which extends beyond the territory subtended by a single coronary artery and recovers within days or weeks. The prognosis was initially thought to be benign, but subsequent studies have demonstrated that both short-term mortality and long-term mortality are higher than previously recognized. Indeed, mortality reported during the acute phase in hospitalized patients is ≈4% to 5%, a figure comparable to that of ST-segment–elevation myocardial infarction in the era of primary percutaneous coronary interventions. Despite extensive research, the cause and pathogenesis of TTS remain incompletely understood. The aim of the present review is to discuss the pathophysiology of TTS with particular emphasis on the role of the central and autonomic nervous systems. Different emotional or psychological stressors have been identified to precede the onset of TTS. The anatomic structures that mediate the stress response are found in both the central and autonomic nervous systems. Acute stressors induce brain activation, increasing bioavailability of cortisol and catecholamine. Both circulating epinephrine and norepinephrine released from adrenal medullary chromaffin cells and norepinephrine released locally from sympathetic nerve terminals are significantly increased in the acute phase of TTS. This catecholamine surge leads, through multiple mechanisms, that is, direct catecholamine toxicity, adrenoceptor-mediated damage, epicardial and microvascular coronary vasoconstriction and/or spasm, and increased cardiac workload, to myocardial damage, which has a functional counterpart of transient apical left ventricular ballooning. The relative preponderance among postmenopausal women suggests that estrogen deprivation may play a facilitating role, probably mediated by endothelial dysfunction. Despite the substantial improvement in our understanding of the pathophysiology of TTS, a number of knowledge gaps remain.
The notion of atherosclerosis as a chronic inflammatory disease has intensified research on the role of cytokines and the way these molecules act and interact to initiate and sustain inflammation in ...the microenvironment of an atherosclerotic plaque. Cytokines are expressed by all types of cells involved in the pathogenesis of atherosclerosis, act on a variety of targets exerting multiple effects, and are largely responsible for the crosstalk among endothelial, smooth muscle cells, leucocytes, and other vascular residing cells. It is now understood that widely used drugs such as statins, aspirin, methotrexate, and colchicine act in an immunomodulatory way that may beneficially affect atherogenesis and/or cardiovascular disease progression. Moreover, advancement in pharmaceutical design has enabled the production of highly specific antibodies against key molecules involved in the perpetuation of the inflammatory cascade, raising hope for advances in the treatment of atherosclerosis. This review describes the actions and effects of these agents, their potential clinical significance, and future prospects.
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.
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EMUNI, FZAB, GEOZS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OILJ, PNG, SAZU, SBCE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract Background Cardiovascular morbidity and mortality are high in chronic kidney disease (CKD) patients compared to the general population. Systemic inflammation may contribute to endothelial ...dysfunction and accelerated atherosclerosis in CKD patients. We assessed the relationship among, endothelial dysfunction, early atherosclerosis and inflammation in predialysis, dialysis and post kidney-transplantation CKD patients. Methods and results We studied 76 consecutive CKD patients; 38 predialysis, 18 haemodialysis and 22 kidney-transplant patients. A group of 65 age and gender matched controls were also studied. In both patients and controls, high-sensitivity C-reactive protein (CRP) levels, systemic endothelial function (brachial artery flow mediated dilation, FMD,%) and carotid artery intima-media thickness (IMT, mm) were measured. CKD patients had increased CRP levels (3.7 1.0–6.0mg/L vs 1.0 0.5–2.1mg/L; p < 0.001), reduced FMD (2.2 1.0–4.0 vs 5.6 4.4–7.1; p < 0.001) and increased IMT (0.82 ± 0.21 vs 0.67 ± 0.16; p < 0.001) values compared to controls. In CKD patients, a significant negative correlation was found between CRP levels and FMD responses ( r = −0.51; p < 0.001) while a significant positive correlation was found between CRP and IMT values ( r = 0.50; p < 0.001). Increased CRP levels were an independent predictor of both abnormal FMD and IMT after adjusting for age, systolic and diastolic BP and total cholesterol. Compared with predialysis and kidney-transplant patients, haemodialysis subjects had significantly lower FMD and higher CRP and IMT values. Conclusions CKD patients taken together have a higher inflammatory status compared to controls. Abnormal FMD responses and IMT values are more commonly found in dialysis patients. Our findings suggest that endothelial dysfunction and atherosclerotic changes correlate with inflammation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, SBCE, SBJE, UL, UPCLJ, UPUK
The Coronary Vasomotion Disorders International Study Group (COVADIS) was established to develop international standards for the diagnostic criteria of coronary vasomotor disorders. The first ...symposium held on the 4-5 September 2013 addressed the criteria for vasospastic angina, which included the following (i) nitrate-responsive angina, (ii) transient ischaemic electrocardiogram changes, and (iii) documented coronary artery spasm. Adoption of these diagnostic criteria will improve the clinical diagnosis of this condition and facilitate research in this field.
Standardization of diagnostic criteria for ischemic symptoms due to coronary microvascular dysfunction (CMD) is needed for further investigation of patients presenting with anginal chest pain ...consistent with “microvascular angina” (MVA). At the annual Coronary Vasomotion Disorders International Study Group (COVADIS) Summits held in August 2014 and 2015, the following criteria were agreed upon for the investigative diagnosis of microvascular angina: (1) presence of symptoms suggestive of myocardial ischemia; (2) objective documentation of myocardial ischemia, as assessed by currently available techniques; (3) absence of obstructive CAD (<50% coronary diameter reduction and/or fractional flow reserve (FFR) >0.80) (4) confirmation of a reduced coronary blood flow reserve and/or inducible microvascular spasm. These standardized criteria provide an investigative structure for mechanistic, diagnostic, prognostic and clinical trial studies aimed at developing an evidence base needed for guidelines in this growing patient population. Standardized criteria will facilitate microvascular angina registries and recruitment of suitable patients into clinical trials. Mechanistic research will also benefit from the implementation of standardized diagnostic criteria for MVA.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Ischemic heart disease involves both “structural” and/or “functional” disorders of the coronary circulation. Structural atherosclerotic coronary artery disease (CAD) is well recognized, with ...established diagnostic and treatment strategies. In contrast, “functional CAD” has received limited attention and is seldom actively pursued in the investigation of ischemic heart disease. Vasospastic angina encompasses “functional CAD” attributable to coronary artery spasm and this “state of the art” consensus statement reviews contemporary aspects of this disorder. Patients with vasospastic angina typically present with angina at rest that promptly responds to short-acting nitrates and is associated with transient ischemic ECG changes. Although spontaneous episodes may be documented, provocative spasm testing may be required to confirm the diagnosis. It is important to diagnose vasospastic angina because it may be associated with major adverse events that can be prevented with the use of appropriate vasodilator therapy (eg, calcium-channel blockers) and the avoidance of aggravating stimuli (eg, smoking). Future studies are required to clarify the underlying pathophysiology, natural history and effective treatments for patients refractory to conventional therapy. (Circ J 2016; 80: 289–298)
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