Ventricular late potential in cardiac syndrome X compared to coronary artery disease.

BACKGROUND: Although ventricular late potential (VLP) was extensively studied in risk stratification of myocardial infarction (MI) patients, comparable researches evaluating presence of VLP in MI-free coronary artery disease (CAD) and cardiac syndrome X (CSX) subjects are scarce. This study aimed to compare presence of VLP between CSX and CAD patients. METHODS: Signal average ECG (SAECG) was performed to 49 patients with a history of typical cardiac pain before undergoing diagnostic coronary angiography (DCA) in Al-Shaab cardiac center, Khartoum, Sudan. QRS duration, duration of the terminal part of the QRS complex with amplitude less than 40 microvolts (LAS40) and the root mean square voltage of the terminal 40 milliseconds (RMS40) of the filtered QRS complex were identified for each patient. Presence of two or more of QRS duration > 120 ms, RMS40 > 38 ms and LAS40 < 20 µV was considered indicative of VLP. Associations between VLP and patients grouped according to DCA results were assessed using appropriate statistical tests. RESULTS: VLP was present in 11.11% (3.63%-24.66%) and 15.38% (2.66%-42.23%) of patients with CAD and CSX respectively. Presence of VLP was comparable in patients with CAD and CSX (OR = 0.69, 95% CI = 0.11-6.05, P = 0.692), even after controlling for the possible variations in gender, age, body mass index (BMI), hypertension and diabetes mellitus in the studied groups. CONCLUSION: Presence of VLP is comparable among CSX and CAD patients.

Efficiency of ranolazine in the patient with microvascular angina, atrial fibrillation and migraine.

Microvascular angina (MVA) is rather a common form of stable ischemic coronary disease (CAD) as that such diagnosis is made in 20-30% of patients who previously underwent coronary angiography. The disease occurs three times more frequently in women than in men irrespective of age. Most of these patients are 45-60 years old. According to available data, the long-term outcome in patients with MVA is comparable with that in general population. MVA characterizes great variability of its course and low response to conventional antianginal therapy. However, patients with MVA experience chest pain, which in most cases tend to strengthen and increase the number of pain episodes, significantly deteriorating the quality of life of these patients. In view of this, the problem of antianginal drugs which can be used in addition to standard therapy remains to be solved. The major role in MVA development plays the decreased coronary flow reserve resulting from evident endothelial dysfunction of small coronary arteries. Ranolazine is a new original antianginal drug which improves left ventricular diastolic filling by selective inhibition of late sodium current leading to more effective coronary vessel filling in diastole. The article presents the case of the successful administration of ranolazine in a woman with MVA and persistent atrial fibrillation.

Coronary microvascular dysfunction: an update.

Many patients undergoing coronary angiography because of chest pain syndromes, believed to be indicative of obstructive atherosclerosis of the epicardial coronary arteries, are found to have normal angiograms. In the past two decades, a number of studies have reported that abnormalities in the function and structure of the coronary microcirculation may occur in patients without obstructive atherosclerosis, but with risk factors or with myocardial diseases as well as in patients with obstructive atherosclerosis; furthermore, coronary microvascular dysfunction (CMD) can be iatrogenic. In some instances, CMD represents an epiphenomenon, whereas in others it is an important marker of risk or may even contribute to the pathogenesis of cardiovascular and myocardial diseases, thus becoming a therapeutic target. This review article provides an update on the clinical relevance of CMD in different clinical settings and also the implications for therapy.

Vitamin D replacement therapy in patients with cardiac syndrome X.

AIMS: The aim of present study was to assess whether vitamin D, with proven beneficial effects on the cardiovascular system, has any effect on angina and exercise-induced ischemia in patients with cardiac syndrome X and low serum vitamin D. METHODS: Patients with cardiac syndrome X and low serum vitamin D3 were studied before and after treatment with an intramuscular injection of vitamin D3 (300,000 units, every other week for 2 months). We determined the angina episode (per day) and several indices of exercise capacity. RESULTS: At the end of the treatment course (75±6 day), a significant increase of serum vitamin D3 occurred and was within the normal range (45±8 ng/ml) and the frequency of angina improved significantly (p=0.003). Exercise duration and maximal work capacity increased significantly (p<0.001). Maximal ST-segment depression (mm) decreased significantly (p=0.001). The calculated Duck treadmill score improved significantly (p=0.001). CONCLUSIONS: Our findings show that vitamin D replacement therapy in patients with cardiac syndrome X and vitamin D deficiency dramatically improves symptoms and signs of ischemia.

The serum pentraxin-3 is elevated in patients with cardiac syndrome X.

OBJECTIVES: Cardiac syndrome X (CSX) is a clinical entity that is defined as normal coronary arteries with angina pectoris and objective sins of ischemia. The correlation between CSX and inflammatory markers such as high-sensitivity C-reactive protein (hs-CRP) is well established, however an association with pentraxin-3 (PTX-3) has not been examined. The aim of this study was to investigate the association between PTX-3 and CSX. STUDY DESIGN: A total of 122 patients (58 female, 64 male, mean age 49.6±5.8 years) with suspected of coronary artery disease (CAD) were included in the study. Those with evidence of ischemia (50 patients with positive treadmill tests, 32 patients with positive myocardial perfusion scintography) underwent coronary angiography (82 patients). Patients with a normal angiogram were considered the CSX group (n=41) and patients with coronary lesions were referred to as the CAD group (n=41). Patients without signs of ischemia served as the control group. Serum PTX-3 and hs-CRP levels were measured in all patients. RESULTS: The CSX group had significantly increased PTX-3 levels relative to the control group (0.46±0.16 vs. 0.23±0.09 ng/ml, p<0.001). However there were no differences in levels of PTX-3 and hs-CRP between the CSX and the CAD groups (PTX-3: 0.46±0.16 vs. 0.51±0.13 ng/ml, p=0.21; hs-CRP: 1.04±0.45 vs. 1.16±0.64 mg/dl, p=0.62). The control group had significantly lower hs-CRP levels (0.73±0.51 mg/dl) when compared to the both CSX and CAD groups (p=0.03 and p=0.002, respectively). Serum PTX-3 levels were weakly correlated with hs-CRP levels (r=0.30, p=0.001). CONCLUSION: PTX-3, a novel inflammatory marker, is elevated in patients with CSX, similar to the well known inflammatory marker hs-CRP, and may be a promising biomarker reflecting inflammatory status in these patients.

Coronary Venous Pressure and Microvascular Hemodynamics in Patients With Microvascular Angina: A Randomized Clinical Trial.

Importance: The role of the coronary venous circulation in regulating myocardial perfusion and its potential in treating microvascular angina is unexplored. Objective: To evaluate whether an increase in coronary venous pressure modifies microvascular resistance in patients with microvascular angina. Design, Setting, and Participants: This was a blinded, sham-controlled, crossover, randomized clinical trial that enrolled participants between November 2021 and January 2023. Participants for this physiology end point study were recruited from the Cardiology Center of the University of Medicine in Mainz, Germany. Patients with moderate/severe angina pectoris (Canadian Cardiovascular Society class 2-4) due to microvascular dysfunction (as defined by the thermodilution-based index of microvascular resistance >25 mm Hg × s). Exclusion criteria were epicardial coronary disease, second- and third-degree atrioventricular block, severe valvular heart disease, cardiomyopathy, and pulmonary or kidney disease. Intervention: Inflation of an undersized balloon placed in the cardiac coronary sinus (CS), hereafter referred to as balloon and the deflated balloon in the right atrium, referred to as sham. Measurements were performed at rest and during maximal coronary hyperemia. Both patients and final assessors were blinded to the randomization sequence. Main Outcomes and Measures: Hemodynamic parameters, including aortic (Pa) and distal (Pd) coronary pressure, coronary sinus pressure (Pcs), right atrial pressure (Pra), and the mean transit time (inverse of blood flow [Tmn]), were measured. Results: A total of 20 patients (median [IQR] age, 69 [64-75] years; 11 female [55.0%]) were included in the study. Two patients (10%) had diabetes, 6 (30%) had hypercholesterolemia, 15 (75%) had hypertension, and 3 (15%) were active smokers. The inflation of the CS balloon caused a significant increase in CS pressure at rest and during hyperemia (300% and 317% increase, respectively, compared with sham, both P < .001), a decrease in hyperemic distal coronary pressure (median [IQR], sham: 92 [80-100] mm Hg; balloon: 79 [75-93] mm Hg; P = .01) and mean transit time (sham: 0.39 [0.23-0.62] s; balloon: 0.26 [0.17-0.46] s; P = .008). As a result, CS occlusion led to a decrease in both resting coronary resistance (median [IQR], sham: 59 [37-87] mm Hg × s; balloon: 42 [31-67] mm Hg × s; P = .005) and the primary end point hyperemic coronary resistance (mean [IQR], sham: 31 [23-53] mm Hg × s; balloon: 14 [8-26] mm Hg × s; P < .001). Conclusion and Relevance: Increased coronary venous pressure led to a reduction of microvascular resistances in patients with microvascular angina, a mechanism with potential implications for the therapy of this complex disease. Trial Registration: ClinicalTrials.gov Identifier: NCT05034224.

Peculiarities of cardiovascular disease in women.

In a review article peculiarities of cardiovascular disease among women are considered. The analysis of published data showed that cardiovascular disease (CVD) is common in women. Gender-specific risk factors include oral contraceptives and menopause. Clinical manifestations, major causes of various forms of cardiovascular disease in women are revealed. It was found that women most often than men have coronary micro vascular disease - X Syndrome, which affects the tiny coronary arteries. Coronary microvascular dysfunction is prevalent in women with chest pain. There is a greater prevalence of no coronary causes of chest pain in the female population, and chest pain is frequently accompanied by abdominal pain, dyspnea, nausea, fatigue, and greater functional disability. Women tend to suffer from more single vessel and two-vessel disease as opposed to the three-vessel disease seen more often in men. It is concluded that specific research is required to identify risk factors of cardiovascular disease in women in Georgia.

AC-Mode of Chemotherapy as a Trigger of Cardiac Syndrome X: A Case Study.

In the period of dynamic development of pharmacological possibilities in the modern oncology, unfortunately, the issue of cardiotoxicity of chemotherapy did not lost its urgent value. Cardiotoxicity implies structural and functional myocardial alteration, together with an increase in the concentration of highly sensitive markers of myocardial necrosis, in particular T and I troponins, and N-terminal pro-BNP, as well as with a subclinical or clinical decrease in the LVEF. It is noteworthy that cardiotoxicity is manifested not only by the development of anthracycline cardiomyopathy with a high risk of convention into heart failure. It also can cause various cardiovascular pathologies, in particular cardiac syndrome X. This study described chemotherapy-induced microvascular angina in 23-year-old otherwise heathy woman. The diagnosis is challenging for doctors, since microvascular flow may be only detected by using functional test.

Association between anxiety disorder and the extent of ischemia observed in cardiac syndrome X.

BACKGROUND: A possible link between the heart and brain has been reported for cardiac syndrome X. Anxiety disorder could be a pathophysiological mechanism for this cardiac chest pain. To the authors' knowledge, a quantitative analysis correlating anxiety with the extent of ischemia has not been done. METHODS AND RESULTS: In this pilot study, we evaluated 20 patients with typical chest pain and completely normal coronary angiograms. These patients were screened with the State Scale and Trait Scale of the State-Trait Anxiety Inventory (STAI). All patients underwent myocardial perfusion scintigraphic imaging. The scintigrams were scored by three experienced readers having no knowledge of the STAI screening results. Patients with a low trait anxiety had significantly less ischemic segments on the myocardial perfusion imaging than patients with a high trait anxiety (1.8 +/- 1.9 vs 3.5 +/- 0.6, P < .05). For state anxiety, no significant differences could be found. CONCLUSION: Cardiac syndrome X patients with high trait anxiety are at risk of having more ischemia.

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

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.

Cardiac rehabilitation for the treatment of women with chest pain and normal coronary arteries.

OBJECTIVE: To explore cardiac rehabilitation (CR) as a treatment for psychological and physiological morbidity in women with chest pain and normal coronary arteries (cardiac syndrome X). DESIGN: Sixty-four women aged 57.3+/-8.6 years (mean +/- SD) with cardiac syndrome X were randomly assigned to an 8-week phase III CR exercise program or symptom monitoring control. All women completed the Hospital Anxiety and Depression Scale, Health Anxiety Questionnaire, and Short Form-36 before and after intervention and at the 8-week follow-up. CR patients underwent physical assessment before and after CR. RESULTS: After CR, patients demonstrated improved symptom severity (2.0+/-0.8 vs 1.26+/-1.1, P=0.009), Hospital Anxiety and Depression Scale depression score (8.0+/-3.4 vs 6.4+/-3.1, P=0.04), total Health Anxiety Questionnaire score (12.0+/-5.5 vs 9.5+/-6.0, P=0.008), health worry (4.5+/-3.1 vs 3.52+/-2.4, P=0.025) and interference (2.4+/-1.8 vs 1.6+/-1.8, P=0.004), SF-36 physical functioning (53.1+/-20.4 vs 62.3+/-23.9, P = 0.006), energy (36.3+/-20.7 vs 49.8+/-19.1, P<0.001), pain (49.9+/-20.7 vs 58.1+/-22.9, P=0.028), and general health (48.8+/-17.9 vs 57.6+/-17.0, P=0.01) not found among the control women. Improvements were maintained at follow-up. CR patients showed significant improvements in Shuttle Walk Test performance (326.8+/-111.0 vs 423.6+/-133.2 m, P<0.001), diastolic blood pressure (84.7+/-9.4 vs 79.7+/-7.3 mm Hg, P=0.007), and body mass index (29.1+/-6.0 vs 28.4+/-6.17 kg/m2, P=0.003). CONCLUSIONS: An 8-week phase III CR program improves exercise tolerance, quality of life, psychological morbidity, symptom severity, and cardiovascular risk factors in women with cardiac syndrome X.

Exercise-induced intra-ventricular gradients as a frequent potential cause of myocardial ischemia in cardiac syndrome X patients.

BACKGROUND: The development of intra-ventricular gradients (IVG) during dobutamine or exercise stress is not infrequent, and can be associated to symptoms during stress. The purpose of this study was to assess the occurrence of IVG during exercise stress echocardiography in cardiac syndrome X patients. METHODS: We prospectively evaluated 91 patients (pts) mean aged 51 +/- 12 years (age ranged 20 to 75 years old), 44 of whom were women. All pts had angina, positive exercise ECG treadmill testing, normal rest echocardiogram and no coronary artery disease on coronary angiogram (cardiac X syndrome). After complete Doppler echocardiographic evaluation with determination of left ventricular outflow tract index (LVOTi), relative left ventricular wall thickness (RLVWT) and left ventricular end-diastolic volume index (LVDVi), all patients underwent stress echocardiography with two-dimensional and Doppler echographic evaluation during and after treadmill exercise. RESULTS: For analysis purpose patients were divided in 2 groups, according to the development of IVG. Doppler evidence of IVG was found in 33 (36%) of the patients (Group A), with mean age 47 +/- 14 years old (age ranged 20 to 72 years) and with a mean end-systolic peak gradient of 86 +/- 34 mmHg (ranging from 30 to 165 mmHg). The IVG development was accompanied by SAM of the mitral valve in 23 pts. Three of these pts experienced symptomatic hypotension. Ten were women (30% pts). 58 pts in group B, 34 of whom were women (59%) (p = 0,01 vs group A), mean aged 53,5 +/- 10,9 years old (age ranged 34 to 75 years) (p = 0,03 vs group A), did not develop IVG. LVOTi was 10,29 +/- 0,9 mm/m2 in group A and 11,4 +/- 1 mm/m2 in group B (p < 0,000); RLVWT was 0,36 +/- 0,068 in group A and 0,33 +/- 0,046 in group B (p < 0,01); LVDVi was 44,8 +/- 10 ml/m2 in group A and 56 +/- 11,6 ml/m2 in group B (p = 0,000). CONCLUSION: 1. A significant number of patients with cardiac X syndrome developed IVG during upright exercise in treadmill. These pts (group A) are mainly males and younger than those who did not develop IVG.2. The development of IVG and mitral valve SAM on exertion seems to be associated with ST segment downsloping during stress testing in patients without epicardial coronary disease.3. The development of IVG and mitral valve SAM seems to be associated with lower LVOTi, lower LVDVi and higher RLVWT.

[Increased myocardial energy expenditure in cardiac syndrome X: More work, more pain]. / Kardiyak sendrom X'li hastalarda artmis miyokart enerji tüketimi: Çok is, çok agri.

OBJECTIVE: The aim of this study was to assess the myocardial energy expenditure (MEE) in patients with cardiac syndrome X (CSX) and to examine its association with exercise electrocardiogram (ECG) parameters. METHODS: A total of 99 patients who underwent coronary angiography and who were diagnosed as having normal coronary arteries were included. The patients were divided into 2 groups based on symptoms and exercise ECG parameters: 56 CSX patients and 43 control patients with a negative stress test. MEE was calculated using transthoracic echocardiography-derived parameters: circumferential end-systolic stress, left ventricular ejection time, and stroke volume. RESULTS: In patients with CSX, the MEE at rest was 28% higher in than the control group (89.2±36.3 vs. 69.8±17.2 cal/minute). Correlation analysis revealed a moderately negative correlation between MEE and the Duke treadmill score (DTS) (ß:-0.456; p<0.001). Receiver operating characteristic analysis with a cut-off value of 74.6 cal/minute for MEE had a sensitivity of 78.1% and a specificity of 75.3% for the prediction of CSX (area under the curve: 0.872; p<0.001). An extra 1 calorie spent per minute at rest increased the likelihood of CSX by about 86% (odds ratio: 1.863). CONCLUSION: This study demonstrated that MEE was greater in CSX patients compared with a control group. Increased MEE was determined to be an independent predictor of CSX. DTS was inversely correlated with MEE. Increased MEE may have a crucial role in CSX pathophysiology.

Gender differences in acute coronary syndromes: focus on the women with ACS without an obstructing culprit lesion.

INTRODUCTION: The etiologies of acute coronary syndromes (ACS) in women expand beyond the traditional paradigm of obstructive epicardial atherosclerotic disease and plaque rupture. Fundamental differences in pathobiology and presentation can partially explain the gender disparity in ACS diagnosis and management, but there is also much we do not know about the spectrum of coronary artery disease in women. Areas covered: This review seeks to explain some key differences between men and women in terms of risk factors, pathophysiology, and clinical presentations, as well as identify areas where more data are needed, focusing on women presenting with ACS but without a culprit lesion to explain their presentation. Literature search was undertaken with PubMed and Google Scholar. Expert commentary: Women with acute coronary syndromes but without plaque rupture or obstructive epicardial atherosclerosis can be difficult to diagnose and manage. Improving care in this underdiagnosed and undertreated population will require early identification of at risk patients, development of better diagnostic strategies, and standardized implementation of guideline-based therapies.

Gene polymorphisms predisposing to cardiac hypertrophy in patients with cardiac syndrome X.

Polymorphisms of the angiotensin-converting enzyme gene and endothelial nitric oxide synthase gene have been suggested to be associated with left ventricular hypertrophy. The aim of our study was to asses the association between above polymorphisms and left ventricular hypertrophy in patients with cardiac syndrome X. The presence of allele 4 of eNOS VNTR polymorphism could predispose to cardiac hypertrophy. The pathological course of postprandial lipemia in patients with CSX may add to the understanding of the CSX pathology.

Gastric myoelectric and autonomic activities and dyspeptic symptoms in cardiological syndrome X patients.

Syndrome X is defined as anginal chest pain accompanied by objective signs of ischemia on exercise testing but with angiographically normal coronary arteries. The aetiology of this syndrome is still not known. The AIM of this study was to evaluate changes in circadian rhythm of gastric myoelectric activity (MA) and autonomic system (AS) and their correlation with dyspeptic symptoms in SX patients. We studied forty consecutive patients, mean age 46+/-8 yrs with syndrome X and 40 sex-, age- and gender-matched healthy volunteers (47+/-5 yrs). The population of syndrome X patients is heterogeneous combining subgroups with normal and low AS activity with high tonic sympathetic drive. Patients with autonomic dysfunction had a high percent of gastric dysrrhythmia with disturbed sympatho-vagal balance particularly at night. We conclude that dyspeptic symptoms in SX patients with autonomic dysfunction are caused mostly by high adrenergic drive affecting stomach myoelectric activity and inducing gastric dysrrhythmias.

Microvascular function, metabolic syndrome, and novel risk factor status in women with cardiac syndrome X.

To characterize microvascular function, candidate risk pathways, and metabolic syndrome prevalence in women with cardiac syndrome X, 52 nondiabetic women with angiographically normal epicardial arteries but >1 mm of planar ST depression during exercise testing (patients) and 24 healthy controls of similar age were recruited. In addition to fasting blood samples and anthropometric measurements, forearm cutaneous microvascular function after iontophoresis of acetylcholine and sodium nitroprusside was assessed by laser Doppler imaging. Despite body mass index correction and a larger proportion on statin therapy, patients had high levels of insulin (p=0.016), triglycerides (p=0.018), intercellular adhesion molecule-1 (p=0.021), von Willebrand factor (p=0.005), and leptin (p=0.005) and lower levels of high-density lipoprotein cholesterol (p=0.042) compared with controls. Consistent with these data, 30% of patients but only 8% of controls fulfilled criteria for the metabolic syndrome as defined by the National Cholesterol Education Program (p=0.015). Endothelium-dependent and -independent microvascular functions were markedly impaired in patients (p<0.001), and the odds ratio for cardiac syndrome X was 7.38 (95% confidence interval 2.2 to 24.7) if the acetylcholine response was <8,710 flux units. In conclusion, women with cardiac syndrome X more commonly have metabolic syndrome and related adiposity, metabolic, and inflammatory derangements. They also have significantly impaired skin microvascular function as assessed by laser Doppler imaging, consistent with generalized vascular dysfunction, a finding with potential diagnostic implications.

Assessment of 25-OH vitamin D levels and abnormal blood pressure response in female patients with cardiac syndrome X.

OBJECTIVE: Vitamin D deficiency is associated with coronary artery disease, hypertension, heart failure, endothelial dysfunction, and metabolic syndrome. The pathophysiology of cardiac syndrome X (CSX) involves many pathways that are influenced by vitamin D levels. This study aimed to investigate the relationship between vitamin D deficiency and abnormal blood pressure response to exercise in patients with CSX. METHODS: This was a cross-sectional and observational study. Fifty females with normal epicardial coronary arteries who presented with typical symptoms of rest or effort angina and 41 healthy age-matched female controls, were included. Patients with cardiomyopathy, severe valvular disease, congenital heart disease, and left ventricular hypertrophy were excluded. All patients underwent stress electrocardiography examination and 25-hydroxy (OH) vitamin D level measurements. RESULTS: Levels of 25-OH vitamin D were significantly lower in CSX patients (9.8±7.3 ng/mL vs. 18.1±7.9 ng/mL; p<0.001). Systolic blood pressure (SBP) (188±15 mm Hg vs. 179±17 mm Hg; p=0.013) and diastolic blood pressure (DBP) (98±9 mm Hg vs. 88±9 mm Hg; p<0.001) during peak exercise were higher in CSX patients. Levels of 25-OH vitamin D were negatively correlated with peak SBP (r=-0.310, p=0.004) and peak DBP (r=-0.535, p<0.001) during exercise. To discard the multicollinearity problem, two different models were used for multivariate analyses. In the first model, metabolic equivalents (METs) (p=0.003) and 25-OH vitamin D levels (p=0.001) were independent predictors. METs (p=0.007), 25-OH vitamin D levels (p=0.008), and peak DBP were determined as independent predictors in the second multivariate model. CONCLUSION: In patients with CSX, 25-OH vitamin D levels were lower than those in controls; moreover, 25-OH vitamin D deficiency was also associated with higher levels of peak DBP during exercise.