Comprehensive treatment of microvascular angina in overweight women - a randomized controlled pilot trial.

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.

A microvascular myocardial infarction in a 16-year-old girl with antiphospholipid syndrome: a case report.

Objective and importance: The antiphospholipid syndrome can manifest itself by silent (or not) myocardial infarction. Clinical presentation: We report the case of a 16-year-old girl who presented a myocardial infarction for whom a coronary-computer tomography did not reveal any coronary abnormalities or obstruction. She had a livedo reticularis on her physical exam. Intervention: The echocardiography showed a normal left ventricular function and a mild eccentric mitral regurgitation. A myocardial magnetic resonance imaging demonstrated transmural necrosis with microvascular obstruction at the inferobasal segment of the left ventricle, suggestive of a microvascular myocardial infarction. The blood test showed elevation of the three antiphospholipid antibodies (lupus anticoagulant, anticardiolipin, and anti-ß2-glycoprotein). The lupus anticoagulant remained positive 12 weeks later, fulfilling the laboratory criteria for antiphospolipid carrier. The associated presence of this microvascular coronary obstruction was strongly suggestive of antiphospholipd syndrome, according to the revised Sapporo criteria. To our knowledge, this is the first reported case of antiphospholipid syndrome manifesting as an acute microvascular myocardial infarction, confirmed by myocardial magnetic resonance imaging. Conclusion: The antiphospholipid syndrome can manifest itself early by a microvascular myocardial infarction. The clinician has to be alerted by a livedo reticularis in these patients, which will be frequently associated with manifestations of antiphospholipid syndrome such as arterial thrombosis and valvulopathies.

The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge.

The incidence of ST segment elevation myocardial infarction (STEMI) has decreased over the last two decades in developed countries, but mortality from STEMI despite widespread access to reperfusion therapy is still substantial as is the development of heart failure, particularly among an expanding older population. In developing countries, the incidence of STEMI is increasing and interventional reperfusion is often not available. We here review the pathophysiology of acute myocardial infarction and reperfusion, notably the temporal and spatial evolution of ischaemic and reperfusion injury, the different modes of cell death, and the resulting coronary microvascular dysfunction. We then go on to briefly characterize the cardioprotective phenomena of ischaemic preconditioning, ischaemic postconditioning, and remote ischaemic conditioning and their underlying signal transduction pathways. We discuss in detail the attempts to translate conditioning strategies and drug therapy into the clinical setting. Most attempts have failed so far to reduce infarct size and improve clinical outcomes in STEMI patients, and we discuss potential reasons for such failure. Currently, it appears that remote ischaemic conditioning and a few drugs (atrial natriuretic peptide, exenatide, metoprolol, and esmolol) reduce infarct size, but studies with clinical outcome as primary endpoint are still underway.

[Cardiac syndrome X--epidemiology, diagnostics, ethiopatoghenesis, prognosis, treatment and latest guidelines]. / Kardiologiczny (sercowy) zespól X--epidemiologia, diagnostyka, etiopatogeneza, rokowanie, leczenie i najnowsze wytyczne.

Since first performed coronary angiography it was noticed that many patients with chest pain, abnormal rest electrocardiogram and positive stress test have normal result of coronary angiogram. The cause of this wasn't known. For the first time this disorder was named cardiac syndrome X by Harvey Kemp in 1973. In the new 2013 European Society of Cardiology guidelines regarding diagnosis and treatment of stable coronary artery disease, term cardiac syndrome X was substituted by "angina with normal coronary arteries". This article elaborates epidemiology, diagnostics, ethiopatoghenesis, prognosis and treatment of patients with diagnosis of term cardiac syndrome X in the light of the latest studies and guidelines.

Coronary Microvascular Dysfunction as a Mechanism of Angina in Severe AS: Prospective Adenosine-Stress CMR Study.

BACKGROUND: Although a common symptom in patients with severe aortic stenosis (AS) without obstructive coronary artery disease (CAD), little is known about the pathogenesis of exertional angina. OBJECTIVES: This study sought to prove that microvascular dysfunction is responsible for chest pain in patients with severe AS and normal epicardial coronary arteries using adenosine-stress cardiac magnetic resonance (CMR) imaging. METHODS: Between June 2012 and April 2015, 117 patients with severe AS without obstructive CAD and 20 normal controls were enrolled prospectively. After exclusions, study patients were divided into 2 groups according to presence of exertional chest pain: an angina group (n = 43) and an asymptomatic group (n = 41), and the semiquantitative myocardial perfusion reserve index (MPRI) was calculated. RESULTS: MPRI values were significantly lower in severe AS patients than in normal controls (0.90 ± 0.31 vs. 1.25 ± 0.21; p < 0.001), and were much lower in the angina group than the asymptomatic group (0.74 ± 0.25 vs. 1.08 ± 0.28; p < 0.001). In logistic regression analysis, the only independent predictor for angina was MPRI (odds ratio: 0.003; p < 0.001). Univariate associations with MPRI were identified for diastolic blood pressure, E/e' ratio, left ventricular volume and ejection fraction, cardiac index, presence of late gadolinium enhancement, and left ventricular mass index (LVMI). In multivariate analysis, LVMI was the strongest contributing factor to MPRI (standardization coefficient: -0.428; p < 0.001). CONCLUSIONS: Our results suggest that, in patients with severe AS without obstructive CAD, angina is related to impaired coronary microvascular function along with LV hypertrophy detectable by semiquantitative MPRI using adenosine-stress CMR. CLINICAL TRIAL REGISTRATION: NCT02575768.

[Microvascular angina. Modern aspects of pathogenesis, diagnostics and treatment].

Microvascular angina was included in the European guidelines on the management of patients with stable coronary artery disease in 2013. Topical aspects of etiology, pathogenesis, clinical course, diagnosis, and treatment of microvascular angina are discussed in this review.

Cardiac syndrome X in Ireland: incidence and phenotype.

BACKGROUND: Cardiac syndrome X (CSX) is typical angina pectoris with objective signs of myocardial ischaemia despite a normal coronary angiogram and may be due to microvascular dysfunction. The incidence of CSX has not been greatly investigated worldwide and its incidence in Ireland is unknown. AIMS: We aimed to determine the incidence of CSX in Cork University Hospital (CUH) and to establish the phenotype of the typical Irish CSX patient. METHODS: All patients undergoing coronary angiography in CUH during regular working hours over a 3-month period were investigated. CSX was diagnosed using standard criteria. An extended recruitment period of 14 months allowed enrolment of a sufficient number of CSX patients to enable phenotyping. RESULTS: Only 5 of 372 (1.3 %) patients undergoing angiography to investigate chest pain met the diagnostic criteria for CSX. None were given a discharge diagnosis of CSX or received cardiology follow-up. Irish CSX patients were predominantly female (88 %) with a mean age of 59.2 ± 6.6 years. Although they were significantly less functionally limited than patients with obstructive CAD, they had an equally substantial impairment in quality of life. CONCLUSIONS: CSX is relatively uncommon in Ireland and is most frequently seen in middle-aged women with hyperlipidaemia. It has significant impacts on patients' quality of life. None of the CSX patients were diagnosed as such, highlighting the lack of awareness or acceptance of this condition in Ireland. These patients require diagnosis and active cardiology follow-up to effectively manage their symptoms.

Different definition of microvascular angina.

We sometimes encounter patients with microvascular angina (MVA), a disease characterized by anginal pain without abnormal coronary arteriographic findings or coronary spasm. More than 40 years have passed since MVA was first confirmed. The terms 'syndrome X', 'cardiac syndrome X' and 'microvascular dysfunction' have also been used to describe conditions similar to MVA, but all with slightly different definitions. The cause of MVA seems almost certain to be organic and functional abnormalities of the small arteries of the heart. Patients with MVA are likely to suffer from endothelial dysfunction and other microvascular abnormalities of both the coronary and peripheral arteries. The major treatment of MVA has been medication, most often calcium channel blockers. The prognosis of MVA is generally excellent, although symptoms remain in many studies. Some MVA patients with accompanying hypertensive heart disease have gone on to develop progressive left ventricular dysfunction, with poor prognosis. The different definitions applied to the terms used to describe this condition, what we refer to here as MVA, can confound issues involved in diagnosis, prognosis and proper treatment. Therefore, it is extremely important to distinguish primary MVA without underlying heart disease from secondary MVA to explore the disease mechanism and examine the clinical characteristics. It is more than 40 years since Likoff first confirmed this disease; therefore, all researchers know that strict diagnostic criteria for MVA should be immediately established.

Dietary Patterns Seem to Influence the Development of Perfusion Changes in Cardiac Syndrome X Patients.

BACKGROUND: Cardiac syndrome X (CSX) is linked with changes in the heart's micro-vasculature, without significant changes in main coronary vessels. According to ESC 2013 stable coronary artery disease criteria, CSX was replaced by Microvascular Angina (MA). While no changes in main coronary vessels are present, most patients still suffer from angina-like chest pains, which significantly diminish their quality of life. CSX is recognized among other coronary diseases and is now considered to be a form of stable angina. In most CSX patients we can visualize perfusion changes in the left ventricle. OBJECTIVES: Since it is well known that the kind of diet can greatly influence the development of coronary disease, our aim was to evaluate the influence of diet on the myocardial perfusion in the group of patients who were diagnosed of CSX. In addition, we tried to verify whether there is any correlation between dietary patterns and perfusion changes visualized in this group of patients. MATERIAL AND METHODS: Toward this goal we screened for the presence of CSX a group of 436 women who suffered from angina-like symptoms and whose routinely performed angiography revealed no changes in coronary vessels. Out of these, 55 women with CSX diagnosis, completed questionnaires regarding their nutritional patterns and underwent both myocardial perfusion studies (MPI) and exercise tests. RESULTS: In the studied group dietary patterns were far from normal values, with the majority of women consuming too much protein, animal fats and sugars in their daily diet, and too low amounts of complex carbohydrates and oils. We were not able to find definite correlations between diet and perfusion changes; however, women whose diet included too high fat and protein intake, seemed to have worse perfusion pattern in MPI. CONCLUSIONS: Nutritional pattern seems to have an impact on development of myocardial perfusion changes in CSX patients.

Coronary slow flow accompanying exertional blurred vision and effects of corticosteroids.

Background Various pathophysiological mechanisms such as microvascular and endothelial dysfunction, small vessel disease, diffuse atherosclerosis, and inflammation have been held responsible in the etiology of coronary slow flow. It is also thought to be a reflection of a systemic slow-flow phenomenon in the coronary arterial tree. Case Report A 44-year-old man presented with chest pain causing fatigue, together with blurred vision for the last 2 years, which disappeared after resting. He had used corticosteroid therapy for facial paralysis 1 month ago. Coronary slow flow was detected in all 3 major coronary arteries on coronary angiography. TIMI measurements for the left anterior descending artery, circumflex, and right coronary artery were 64, 72, and 55, respectively. In fundus fluorescein angiography, retinal vascularity was normal, the arm-to-retina circulation time was 21.8 s, and the arteriovenous transit time was 4.3 s. In the early arteriovenous phase, choroidal filling was long, with physiological patchy type. Diltiazem 90 mg/day and acetylsalicylic acid 100 mg/day were given. His chest pain and visual symptoms disappeared after medical treatment. Conclusions Physicians should be aware that glucocorticoids might cause an increase in the symptoms of coronary slow flow and some circulation problems, which might lead to systematic symptoms.

Angina pectoris in patients without flow-limiting coronary artery disease (cardiac syndrome X). A forest of a variety of trees.

Coronary heart disease (CHD) represents an important problem worldwide. At present, more women than men are evaluated for CHD and it has been recognized that the prevalence of this pathology in women is at least the same as in men. We have learned that cardiac syndrome X (CSX) is frequent because worldwide each year millions of people (mostly women) with angina pectoris without flow-limiting epicardial pathology are identified. Data from large myocardial infarction registries suggest a 5% to 25% prevalence of cases without flow-limiting coronary pathology. It must, however, be considered that these people are said to have normal coronary arteries by visual analysis of biplane coronarography. On the other hand, as demonstrated from autopsy, and in vivo by ultrasound intravascular studies, it would be more appropriate to say that in the majority of these cases no obstructive or flow-limiting coronary pathology was detected by coronarography. In CSX, endothelial dysfunction and microvascular dysfunction, sometimes with coronary microvascular spasm and epicardial coronary artery spasm, have been recognized as pathophysiologic mechanisms. In CSX, symptoms and pathologic signs are the same in patients with flow-limiting coronary pathology. The difference lies in the fact that the mechanisms of myocardial ischemia are microvascular and flow-limiting epicardial coronary pathology is absent. By interplay, the pathologic entities at work in CSX are linked with poor long-term outcome. The prevalence of these outcomes is probably smaller than in patients with flow-limiting coronary pathology but we lack precise values. Nonetheless, severe cardiovascular complications are frequent in CSX and it is thus the pathology is not benign. Drugs used in coronary ischemic disease are empirically prescribed to treat CSX, but we lack data from specific trials. It seems that statins and ranolazine might exert positive effects. However, specific research to target interventions in CSX would be necessary.

[Microvascular angina].

Microvascular angina is a rather widely spread disease which is associated with high rate of unfavorable outcomes and substantial economical cost of examination and treatment. However problems of noninvasive diagnostics of the disease have not been entirely solved as well as clear-cut algorithm of management has not been elaborated. We present in this paper consideration of contemporary aspects of etiology, pathogenesis, clinical course, diagnosis, and treatment of microvascular angina in accordance with European recommendations on management of patients with stable ischemic heart disease.

[Microvascular angina in women: a diagnostic and therapeutic challenge]. / Microvasculaire angina pectoris bij vrouwen: een diagnostische en therapeutische uitdaging.

Gender differences play an important role in coronary heart disease (CHD). Not only in the presentation of symptoms, but also in their underlying pathophysiology. Women with persistent angina without obstructive coronary artery disease (CAD) pose a diagnostic and therapeutic challenge. Half of these women have microvascular coronary dysfunction (MCD). The 2013 guidelines on management of stable angina now acknowledge this condition, but our understanding of MCD is still limited. In this clinical case presentation we elaborate on contemporary methods of diagnosing and managing microvascular angina based on the cases of two women who attended our outpatient clinic. The availability of non-invasive tools to diagnose MCD is still limited. Current treatment is based on reduction of cardiovascular risk factors but physicians and patients should be aware that although therapy usually reduces symptoms, they do not completely disappear. More research on diagnostic methods and effective therapy for MCD is eagerly awaited.

Angina pectoris and myocardial ischemia in the absence of obstructive coronary artery disease: practical considerations for diagnostic tests.

Angina and myocardial ischemia without obstructive coronary artery disease are common clinical findings, often neglected for the assumption of a good prognosis. Most often, such patients are neither further investigated nor offered specific treatment beyond reassurance. However, the absence of significant coronary stenoses on angiography does not necessarily imply a "healthy" coronary tree. In such cases, myocardial ischemia may result from different types of functional disease involving the epicardial coronary arteries, the coronary microcirculation, or both; an accurate assessment of these components should be systematically performed after exclusion of organic epicardial disease because a correct diagnosis has relevant prognostic and therapeutic implications. Here we discuss the basic principles of diagnostic tests in this setting and propose a diagnostic sequence of reasonable practical implementation that may help identify patients at risk of future cardiac events.