Development Of Angina Research Articles

Exploring the Genetic Roles of Diet and Other Modifiable Risk Factors in the Risk of Angina: A Causal Investigation Using Mendelian Randomization in UK Biobank and FinnGen Cohorts.

Angina pectoris, a debilitating manifestation of coronary artery disease, has been associated with various modifiable risk factors. However, the causal underpinnings of these associations remain unclear. This study leveraged Mendelian randomization (MR) to investigate the causal roles of dietary patterns, smoking behaviors, body mass index (BMI), and physical activity in the development of angina. Two-sample MR analyses were performed using summary-level data from large-scale genome-wide association studies (GWASs) and biobank resources, including the UK Biobank (UKB) and FinnGen cohorts. Genetic variants associated with various types of exposure such as fruit and salad intake, smoking initiation and intensity, BMI, and physical activity were used as instrumental variables, and their causal effects on angina risk were assessed. In the UKB cohort (336,683 individuals, 10,618 cases), genetically proxied fruit (OR = 0.95, 95% CI: 0.93-0.97) and cheese intake (OR = 0.98, 95% CI: 0.97-0.99) were associated with decreased angina risk, while smoking initiation (OR = 1.01, 95% CI: 1.002-1.012), maternal smoking (OR = 1.06, 95% CI: 1.03-1.09), and BMI (OR = 1.01, 95% CI: 1.01-1.02) were associated with increased risk. In the FinnGen cohort (206,008 individuals, 18,168 cases), fruit (OR = 0.30, 95% CI: 0.17-0.53) and salad intake (OR = 0.31, 95% CI: 0.12-0.55) were found to be protective, while smoking initiation (OR = 1.20, 95% CI: 1.04-1.37) and intensity (OR = 1.15, 95% CI: 1.04-1.26) and BMI (OR = 1.31, 95% CI: 1.18-1.47) increased angina risk. This study provides robust evidence for the causal roles of various modifiable risk factors associated with angina development, highlighting the potential benefits of dietary interventions that promote increased fruit and vegetable consumption, smoking cessation, and weight management to mitigate angina risk. Further investigation is needed to generalize these findings to populations with diverse genetic backgrounds, lifestyles, and environmental exposures.

Contribution of <i>AGTR</i> 1 Promoter Region Polymorphism to the Progression and Outcome of Sepsis in Patients with Various Comorbidities

Blood pressure dysregulation and circulatory failure are major contributors to the progression of sepsis and especially septic shock. One of the genes affecting the vascular endothelium and arteriolar tone is the angiotensin II receptor 1 gene (AGTR1). The AGTR1 rs275651 single-nucleotide polymorphism is associated with the development of angina, high altitude pulmonary edema, and hypertension. The significance of the AGTR1 rs275651 polymorphism in sepsis, particularly in patients with significant comorbidity, has not been studied previously.The aim of the study was to determine the impact of AGTR1 functional polymorphism on sepsis outcome in patients with various comorbidities, including cardiovascular disease and type 2 diabetes mellitus.Material and methods. A prospective study included 144 ICU patients of two clinical hospitals in Moscow, aged 18-75 years with clinical signs of sepsis (Sepsis-3, 2016).Results. In the group of patients with cardiovascular diseases, carriers of the TT AGTR1 rs275651 genotype had a lower mortality rate compared with carriers of the A allele (25 deaths out of 33 versus 16 out of 16, respectively, P=0.041, Fisher's exact test; P=0.0019, log-rank test). In the group of patients with diabetes mellitus (n=62), we also found significant differences in sepsis outcome based on the AGTR1 rs275651 genotype variant. The subgroup of TT AGTR1 rs275651 genotype carriers demonstrated significantly lower mortality compared with TA, AA genotypes carriers (27 deaths out of 41 and 20 out of 21, respectively, P=0.012, Fisher's exact test; OR=10.37; 95% CI: 1.26 to 85.5; P<0.0001, log-rank test).Conclusion. We found an association of the functional polymorphism AGTR1 -777 T>A (rs275651) with sepsis outcome in ICU patients with high-value baseline comorbidity: carriers of the more common TT genotype had lower mortality compared to carriers of the minor A allele.

Painful left bundle branch block: A syndrome with a particular clinical significance

The development of angina in the setting of new-onset left bundle branch block (LBBB) that resolves at the same time with the disappearance of LBBB, without coexistent myocardial ischemia, denotes the painful LBBB syndrome. In this illustrative case report we describe a young male patient with painful LBBB syndrome. The LBBB was rate-dependent occurring during exercise and the patient was successfully treated with bisoprolol. We also provide a concise review of the literature and we briefly discuss the diagnosis and management of this clinical entity.<Learning objective: Painful left bundle branch block syndrome is a rare clinical entity, that is possibly underdiagnosed. The exclusion of coronary artery disease in a patient with angina pectoris occurring simultaneously with the development of left bundle branch block should raise the suspicion of this syndrome.>

Investigation of Malondialdehyde (MDA), Homocysteine (Hcy) and C- reactive protein (CRP) in sera of patients with Angina Pectoris

Homocysteine (Hcy) has been considered as an independent risk factor for coronary artery disease (CAD Oxidative stress and free radicals are known to have important roles in the development ofAngina Pectoris. Oxidative stress is present in cardiovascular diseases (CVDs), and hyperhomocysteinemia, an independent risk factor for these diseases, may play a role in inducing production of oxygen free radicals. The aim of this study was to determine a possible relationship between blood serum Hcy levels and lipid peroxidation in patients suffering from Angina Pectoris (AP).To evaluate the possible role of homocysteine (Hcy) in inducing oxidative stress in Angina Pectoris(AP), plasma homocysteine( Hcy), plasma malondialdehyde (MDA) and C reactive protein (CRP) were measured in 60 unstable Angina Pectoris patients, we tested 30 healthy volunteers. Hcy was measured by an enzymatic colorimetric method and MDA, an index of lipid peroxidation, by spectrophotometer. Serum Hcy levels were significantly higher in angina pectories (AP) patients than the controls (23.2±8.0 vs 10.76 ± 2.55 micromol/L; P

ASSOCIATION OF THE VARIANTS OF NUCLEOTIDE SEQUENCE OF THE GENE ADIPOQ WITH PLASMATIC LEVEL OF ADIPONECTIN, THE GRADE OF CORONARY ATHEROSCLEROSIS SEVERITY AND RATE OF CARDIOVASCULAR DISEASES

Aim. The search for genetic markers of ADIPOQ, associated with the level of adiponectin and development of coronary atherosclerosis.Material and methods. To the study, patients included, who had undergone diagnostic coronary arteriography in 2011-2012 in the NMRCPM with assessment of the severity of coronary atherosclerosis. The level of adiponectin was measured in plasma with the test-system based on the immune enzyme analysis. Genetic variants rs17300539, rs182052 and rs266729 gene ADIPOQ were measured realtime (Applied Biosystems, 7500 Real Time PCR System). Alleles of the studied variants were summarized by a unified score of genetic risk (SGR).Results. To the study, 447 patients included, of those 319 males (70,7%). Median of age was 61 [55-69] y.o. All patients were selected to 2 groups by SGR (≤2 and &gt;2, respectively). Groups differed by the level of adiponectin 7,64 vs 8,29 mcg/mL (р=0,01), total cholesterol 4,60 vs 5,00 mM/L (p=0,03), cholesterol of low density lipoproteides 2,8 vs 3,09 mM/L (p=0,03), and the rate of unstable angina development 2,15% vs 6,8% (р=0,02) and type 2 diabetes 11,8% vs 21,1% (р=0,01), respectively. There was no difference in the groups by Syntax and Gensini score.Conclusion. Genetic score based on the three variants of ADIPOQ does determine the plasmatic level of adiponectin and risk of unstable angina and diabetes, but not the grade of coronary atherosclerosis.

Ivabradine in practice

Ivabradine is an innovation in the cardiovascular fraternity with specific heart rate-lowering property, which expresses selective action on pacemaker activity in the sinoatrial node of the heart, resulting into important clinical benefits for improvement in coronary perfusion and pump efficiency. Ivabradine demonstrated substantial antianginal and anti-ischemic efficacy, improvement in exercise capacity and in quality of life in monotherapy or in combination with beta-blockers. The analysis of pooled data from ivabradine angina development programme assessing the antianginal efficacy of ivabradine across several different subgroups provided clinical evidence that ivabradine diminishes angina in all types of patients, whatever their age, sex, severity of angina, and revascularization status, history of previous myocardial infarction, peripheral vascular disease, or diabetes. These clinical benefits make ivabradine an important agent for symptomatic treatment of patients with angina pectoris. The important role of ivabradine in the management of patients with chronic heart failure (HF) is well established and supported by its benefits in prevention of morbidity and mortality demonstrated in SHIFT trial. Efficacy and tolerability of ivabradine in patients with HF, including those with different clinical profiles (elderly; severe disease; low blood pressure; comorbidities, including renal dysfunction, diabetes, chronic obstructive pulmonary disease), make ivabradine particularly pertinent for achievement of all targets in the treatment of HF, including improvement of symptoms and well-being, as well as outcomes. The available wealth of evidence supports the important place of ivabradine as an essential therapeutic modality to enhance the management of patients with angina or chronic HF.

Risk Stratification in Patients With Aortic Stenosis Using Novel Imaging Approaches.

The prevalence of calcific aortic stenosis increases with age, occurring in 3% to 5% of individuals aged >75 years.1,2 The narrowing of the aortic valve is driven by a highly complex and intricately regulated process of inflammation, fibrosis, and calcification, which eventually results in leaflet immobility and the associated hemodynamic consequences.3 In response to the narrowed valve, left ventricular hypertrophy is initially adaptive to restore wall stress and cardiac performance. Ultimately, adverse events, such as symptoms, heart failure, and death, occur as the left ventricle decompensates. This transition from adaptation to decompensation is driven by progressive myocyte death and myocardial fibrosis.4–6 Therefore, it is important to consider aortic stenosis as a condition that affects both the valve and the myocardium.5,6 Indeed, contemporary guidelines recommend aortic valve replacement in patients with severe aortic stenosis and evidence of advanced ventricular decompensation, defined by either the presence of symptoms or an impaired systolic ejection fraction <50%.7,8 The current strategy relies heavily on the timely identification of symptoms. However, the poor prognosis associated with the development of angina, exertional dyspnea, and syncope first described by Ross and Braunwald4 in 1968 was based on younger patients with bicuspid or rheumatic disease (average age of 63 years at the time of death). Establishing symptoms in the more elderly population encountered in current clinical practice is more challenging because of their comorbidities and often sedentary lifestyles. Moreover, it is now widely recognized that left ventricular ejection fraction is not a sensitive marker of myocardial dysfunction,9,10 and impairment in ejection fraction is often a late manifestation that may not be reversible.11,12 Furthermore, there is an urgent need to improve our understanding of the pathogenesis of aortic stenosis, both …

MicroRNA 21 is upregulated following coronary artery stenting and genetic deletion limits neointima formation

Purpose: Atherosclerosis in coronary arteries causes luminal narrowing, restriction of blood flow and the development of angina. Percutaneous Coronary Intervention (PCI) with stents is a common treatment. In-Stent Restenosis (ISR) or luminal renarrowing following PCI is due to the proliferation and migration of smooth muscle cells (VSMCs) and deposition of extracellular matrix (ECM). MicroRNAs (miRs) are small non-coding 19-25 nucleotide RNA species that post-transcriptionally regulate gene expression in health but have also been implicated in many disease settings. MiR-21 levels are dysregulated in atherosclerotic lesions, following vascular injury and have been implicated in VSMC proliferation and migration. We hypothesised that miR-21 promotes ISR. Methods: Male Welsh Landrace swine 18-22kg received bare-metal stents (BMS) and were euthanised at 0, 7 or 28 days (n=4/group). Total RNA was extracted from one half of the stented porcine coronary arteries. MiR-21 expression levels were measured by quantitative real-time polymerase chain reaction. In situ hybridisation was also conducted on stented vessels. For mouse studies, miR-21 knockout (KO) and wild type (WT) controls were used. The aorta of a donor mouse was stented and interposition grafted into a recipient mouse of identical genotype. Grafts were harvested at 0 or 28 days. Following electrochemical dissolution of the stent, tissues were paraffin embedded and morphometric analysis conducted on serial sections throughout the stented segment. Results: In the porcine model, miR-21 levels were upregulated at both 7 and 28 days by a factor of 5.3±1.1 and 3.8±1.3 respectively (p<0.001 for both). Insitu hybridisation demonstrated elevated expression of miR-21 throughout the vessel wall but at a high level in the developing neointima. No difference was observed between miR-21 KO (n=3) and WT (n=9) mice in total vessel, luminal, medial or neointimal area at day 0. Comparing miR-21 KO (n=6) v miR-21 WT (n=12) mice at 28 days significantly less neointimal area and neointimal:medial ratio was observed (0.12±0.02mm2 v 0.18±0.02mm2; 1.47±0.22 v 2.11±0.17, p<0.05 for both). As a consequence luminal area was significantly reduced in the miR-21 WT mice (0.22±0.02mm2 v 0.32±0.03mm2, p<0.01). No significant difference was observed in total vessel or medial area at 28 days. Conclusions: Mir-21 is upregulated in porcine coronary arteries following stenting with BMS. Genetic deletion of miR-21 in a murine model of stenting attenuates the development of neointimal formation and ISR. Targeting miR-21 to reduce ISR maybe of use in a clinical setting.

Circulating secretory type IIA phospholipase A2, lipoprotein (a) and soluble cellular adhesion molecule levels in patients with angina pectoris

Objectives To examine the plasma levels of secretory type IIA phospholipase A2 (sPLA 2-IIA), lipoprotein (a) [Lp(a)], soluble intercellular adhesion molecule-1 (sICAM-1) and soluble platelet endothelial CAM-1 (sPECAM-1), as well as ICAM-1 (K469E) and PECAM-1 (Leu125Val) gene polymorphisms, in patients with unstable angina pectoris (UAP) and stable AP (SAP). Design and methods We enrolled 75 patients with SAP, 72 with UAP and 80 controls without angina. Blood samples were obtained before angiography. Results The concentrations of sPLA 2-IIA, sICAM-1 and sPECAM-1 were higher for UAP patients than for SAP patients and controls, and the level of Lp(a) was higher for UAP patients than for controls. Lp(a) and sPLA 2-IIA levels were significantly correlated, and high plasma Lp(a) level (≥ 300 mg/L) was an independent risk factor for angina. Conclusion Lp(a) may play an important role in the development of angina. Further research should investigate the role of sPLA 2-IIA, sICAM-1 and sPECAM-1 in UAP.

Serum deoxyribonuclease I activity can be used as a novel marker of transient myocardial ischaemia: results in vasospastic angina pectoris induced by provocation test

Serum deoxyribonuclease I (DNase I) activity has recently been highlighted as a potential diagnostic marker for detection of acute myocardial infarction. To evaluate whether serum DNase I activity is useful for detection of myocardial ischaemia, we investigated alteration of its levels after onset of vasospastic angina pectoris (VSAP), resulting in transient myocardial ischaemia, induced by the intracoronary ergonovine provocation test. Twenty-nine consecutive patients with suspected VSAP were subjected to the test. Patients were categorized as VSAP-positive (n = 13) or -negative (n = 16) based on development of angina. Serum samples were examined for DNase I activity before, immediately after, and 3, 6, and 24 h after the provocation tests. The serum DNase I activity increased significantly from the baseline 3 h after the provocation test in 11 patients of the VSAP-positive group whose levels of troponin T were within the normal range. Median of the percentage differences from the baseline in serum DNase I activity 3 h after the test was 32.1% (25th and 75th percentile: 28.6 and 42.0%, respectively; P = 0.000012). In the VSAP-negative group, levels of DNase I activity remained unchanged at any point of time after the provocation test. Transient myocardial ischaemia resulting from VSAP induces a significant elevation of serum DNase I activity. Therefore, serum DNase I activity may be applicable as a useful marker for detecting transient myocardial ischaemia.

Postoperative Outcome in Aortic Stenosis With Diastolic Heart Failure Compared to One With Depressed Systolic Function

In patients with aortic stenosis (AS), the clinical outcome worsens after the development of angina, syncope, and heart failure. This study was performed to elucidate whether the outcome with AS was also poor in patients with diastolic heart failure. Fifty-two patients who had undergone aortic valve replacement (AVR) for AS were retrospectively classified into 3 groups (G) on the basis of LV ejection fraction (EF) and pulmonary wedge pressure (PWP): G-1) normal LVEF, low PWP (EF > or = 45% and PWP < 16 mmHg; n = 35), G-2) normal LVEF, high PWP (EF > or = 45% and PWP > or = 16 mmHg; n = 8), and G-3) low LVEF (EF < 45%; n = 9). Among these 3 groups, we compared the outcome after AVR. None of the patients died after the operation in AS with preserved LVEF irrespective of the PWP, whereas there were 3 cardiac deaths in AS with low EF irrespective of the PWP. In patients with AS, diastolic heart failure developed in addition to systolic heart failure. The development of LV systolic dysfunction in AS was regarded as poor during the postoperative course, but diastolic heart failure did not affect the outcome. The occurrence of heart failure with preserved systolic function may have a slightly better prognosis and may still be suitable for AVR.

Silent Myocardial Ischemia

Silent myocardial ischemia is defined as objective documentation of myocardial ischemia in the absence of angina or anginal equivalents. Since its original description in the 1970s, it has undergone intensive investigation, and its clinical significance is now well established. This review will serve as an update on the pathophysiology, detection, prevalence, prognosis, and treatment of silent ischemia in both asymptomatic patients and those with angina, whether stable or unstable. ### Pain Studies No discussion of silent ischemia is complete without consideration of the cardiac pain mechanism. Although much has been learned about this subject, much is still uncertain. The afferent fibers that run in the cardiac sympathetic nerves are usually thought of as the essential pathway for the transmission of cardiac pain (Figure 1). The atria and ventricles are abundantly supplied with sympathetic sensory innervation; from the heart, the sensory nerve endings connect to afferent fibers in cardiac nerve bundles, which in turn connect to the upper 5 thoracic sympathetic ganglia and the upper 5 thoracic dorsal roots of the spinal cord. Within the spinal cord, impulses mediated by this sympathetic afferent route probably converge with impulses from somatic thoracic structures onto the same ascending spinal neurons. This would be the basis for cardiac pain referred to the chest, wall, arm, back etc. In addition to this “convergence-projection theory,” the contribution of vagal afferent fibers must be acknowledged for an explanation of cardiac pain referred to the jaw and neck. How these vagal fibers are activated remains unclear. Furthermore, somatic localization of ischemic pain cannot predict the site of myocardial ischemia (anterior, inferior, or lateral) from one patient to the next. Figure 1. Mechanisms of cardiac pain. From Droste and Roskamm (used with permission).4 The actual “trigger” that stimulates the sensory nerve endings remains elusive. If a chemical pain stimulus is involved, …

Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis

PURPOSE: Obstructive intramural coronary amyloidosis is an unusual complication of systemic amyloidosis. SUBJECTS AND METHODS: We review the characteristics of 11 patients seen at the Mayo Clinic (Rochester, Minnesota) from January 1, 1960, to June 1, 1999, with intramural cardiac amyloidosis diagnosed at autopsy or after examination of an explanted heart. RESULTS: Symptomatic ischemic heart disease resulting from obstructive intramural coronary amyloidosis was found in 11 patients (8 men, 3 women). The mean (±SD) age at the diagnosis of primary amyloidosis was 62 ± 12 years. All patients had angina pectoris; angina was the presenting symptom of primary amyloidosis in 6 patients. Unstable coronary syndromes occurred in 7 patients and congestive heart failure in 8. New electrocardiographic abnormalities after the development of angina were common and included ischemic changes, bundle branch block, and dysrhythmias. Low voltage was seen in only 2 patients. All 7 patients who underwent coronary angiography had normal or clinically insignificant findings. Endomyocardial biopsy was performed on 4 patients; amyloid was found in 3 patients, none of whom had obstructive intramural coronary amyloidosis. The diagnosis of obstructive intramural coronary amyloidosis with associated myocardial injury was established only at autopsy or after examination of the explanted heart after cardiac transplantation. The mean time to death or cardiac transplantation after symptoms of cardiac ischemia developed was 18 ± 20 months. CONCLUSIONS: The diagnosis of ischemic heart disease resulting from obstructive intramural coronary amyloidosis is difficult to establish before death or cardiac transplantation. Although the condition has a poor prognosis, its accurate recognition may have therapeutic implications, because some patients may benefit from treatment, including systemic chemotherapy or cardiac transplantation.

Valvular disease in pregnancy.

Previously asymptomatic mitral stenosis can lead to remarkably sudden development of life-threatening pulmonary edema in pregnancy and the patients, often immigrants from the developing world, may be unaware that they have heart disease. Diagnosis and treatment need to be rapid and effective. Left ventricular outflow tract obstruction may also lead to trouble in pregnancy with the development of angina and left ventricular failure. Regurgitant valve disease is much better tolerated in pregnancy than valvular stenosis, but mitral valve repair, usually feasible for nonrheumatic prolapsing mitral valves, should be carried out before pregnancy if regurgitation is severe. The treatment of women with Marfan's syndrome who already have aortic root widening but desire children remains very difficult, both with regard to the mother's safety and in relation to the dominant inheritance of the condition. Advice to women with artificial valves desiring pregnancy remains controversial, with continuation of warfarin increasingly favored over transfer to heparin in Europe. The use of bioprostheses in young women anticipating future pregnancy is also fading due to mounting evidence of accelerated deterioration of such bioprostheses during pregnancy.

Long Term Efficacy and Safety of Carvedilol, a New β-Blocking Agent with Vasodilating Properties, in Patients with Chronic Ischaemic Heart Disease

The long term efficacy and safety of Carvedilol, a new vasodilating β-blocking drug, was evaluated in 32 patients with chronic stable angina, using a randomised double-blind, placebo-controlled protocol for 1 month, followed by an open phase of 5 months during which all patients received Carvedilol 25mg twice daily. Treadmill exercise testing was performed at the end of 1 (double-blind), 3 and 6 months (open phase). Five patients were withdrawn from the study, 2 because of adverse events and the rest because of noncompliance or surgical intervention during the study. Exercise time (mean ± SD) had improved significantly on Carvedilol at the end of the double-blind phase (1 month) from 6.6 ± 0.6 to 7.7 ± 0.7 min (p < 0.05) and this was maintained at 3 and 6 months (8.3 ± 0.7 min, p < 0.01 and 8.5 ± 0.7 min, p < 0.005, respectively). In the group started on placebo, exercise time also improved significantly from 6.4 ± 0.5 to 7.3 ± 0.5 min (p < 0.05), but this was further improved at 3 (8.0 ± 0.7 min) and 6 months (8.9 ± 0.8 min) with Carvedilol (p < 0.02 and p < 0.0001, respectively). Time to 1mm ST-segment depression did not alter significantly with placebo (4.8 ± 0.6 to 4.9 ± 0.4 min), but was significantly improved by Carvedilol at 1, 3 and 6 months (p < 0.05, p < 0.01 and p < 0.005, respectively). Similarly, time to development of angina during exercise did not alter with placebo (5.1 ± 0.4 to 5.4 ± 0.4 min), but was significantly increased by Carvedilol at 1 month (5.4 ± 0.4 to 6.3 ±0.6 min, p < 0.02), and this was maintained on long term therapy at 3 and 6 months (6.3 ±0.5 min, p < 0.005, and 6.9 ± 0.5 min, p < 0.001, respectively). Peak exercise heart rate and double product were reduced by active therapy only, at 1 month (124 ± 5 to 107 ± 3 beats/minute, p < 0.0001; 197 ± 11 to 160 ± 9, p < 0.0001), 3 months (108 ± 4, p < 0.0001; 162 ± 9, p < 0.001) and 6 months (108 ± 3, p < 0.0005; 157 ± 7, p < 0.0002), respectively. These results suggest that Carvedilol is a well tolerated and effective β-blocker; however, the lack of any significant difference in exercise time with placebo suggests that the dose of 25mg twice daily is insufficient in the management of chronic stable angina.

Systemic and coronary hemodynamic effects of bepridil in patients with depressed left ventricular function

To assess the effects of oral bepridil therapy (10–14 days) on cardiac performance and myocardial energetics in the presence of depressed left ventricular function, systemic and coronary hemodynamic effects and neurohumoral effects were evaluated in 7 patients with coronary artery disease and reduced ejection fraction at control, submaximal, and maximal pacing rates during atrial pacing stress. After bepridil therapy, arterial, right atrial, and left ventricular filling pressures as well as systemic vascular resistance and left ventricular stroke work index did not change, suggesting no deleterious effects of bepridil on cardiac performance in patients with reduced ejection fraction. Rate-pressure product, myocardial oxygen consumption, coronary sinus blood flow, myocardial lactate extraction, and catecholamine balance remained unchanged. Development of angina during pacing showed a variable response to bepridil. We conclude that despite its potential negative inotropic effect, bepridil does not exert deleterious effects on hemodynamics or left ventricular performance. The mechanism for its beneficial antianginal effect may be due to favorable redistribution of myocardial blood flow to ischemic zones; no clear effect on anginal threshold or sympathetic tone could be demonstrated in these patients.

Antianginal, hemodynamic and coronary vascular effects of captopril in stable angina pectoris

A pilot study was performed to assess the short-term effects of intravenous captopril on anginal threshold and systemic and coronary hemodynamics in patients with stable angina pectoris. Twelve patients with documented coronary artery disease, stable angina pectoris and normal left ventricular function were studied by an incremental atrial pacing stress test before and after intravenous captopril (n = 8) or placebo (n = 4). There were no significant differences in the extent of coronary disease or left ventricular function between the 2 groups and resting plasma-renin levels were normal. Captopril increased the time to angina (14 ± 4 to 19 ± 5 minutes, p <0.05), increased heart rate at development of angina (126 ± 7 to 142 ±7 beats/min, p <0.05) and tended to increase coronary blood flow (229 ± 154 to 296 ± 259 ml/min, p = 0.11) and decrease coronary vascular resistance (53 ± 10 to 47 ± 3 dynes s cm −5/1,000, p = 0.11) at peak stress without alteration in systemic hemodynamics. No significant changes were seen after placebo administration. Therefore, intravenous captopril appears to cause a short-term increase of coronary vascular reserve, and anginal threshold in patients with chronic stable angina. This effect appears to be independent of inhibition of the systemic renin-angiotensin system or systemic hemodynamic changes.

Current Therapy for Hypercholesterolemia

THE EVIDENCE is now in that lowering cholesterol levels reduces the risk of coronary heart disease (CHD). A century of animal data as well as morphological, genetic, and metabolic studies in man point to a strong association between serum cholesterol levels and coronary artery disease. Prospective epidemiologic studies show a graded relationship between serum cholesterol and coronary risk extending to cholesterol levels below 4.14 mmol/L ( 1 Clinical trials performed in man provide the final validation of the cholesterol-atherogenesis connection. In the Lipid Research Clinics Coronary Primary Prevention Trial, over a 7-year period a 12.5% decrease in low-density lipoprotein (LDL) cholesterol levels was associated with a 19% decrease in the incidence of myocardial infarction and CHD death. 2,3 In addition, treatment was associated with a significant reduction in the development of angina, a positive exercise test, and the need for

Enhanced prediction of major cardiac events after myocardial infarction using exercise radionuclide ventriculography.

Exercise radionuclide ventriculography (RVG) was performed 7-12 days after acute myocardial infarction (MI) in 153 patients to assess its value in identifying those at risk of serious recurrent cardiac events. In addition to electrocardiogram (ECG) features of the exercise test, clinical and hemodynamic features were also considered: the exercise test was abnormal if there was a fall in blood pressure of 10 mmHg or more, development of angina, or inability to complete three minutes of exercise. RVG was used to measure left ventricular ejection fraction and to assess wall motion at rest and at peak exercise. After a median follow-up of 14 months, there were 18 cardiac events: six deaths and 12 patients with recurrent MI. In addition, 18 patients underwent coronary artery bypass surgery; the decision to perform surgery was predicted by ST segment depression or a fall in blood pressure during exercise (p less than 0.005). The sensitivity of the exercise test for identifying patients with a cardiac event increased progressively as additional parameters were considered in a cumulative fashion; hence, ST depression identified 28% of patients with events, whereas addition of clinical and hemodynamic parameters increased this to 61%. The addition of RVG increased the sensitivity further to 88%, but with a specificity of 50%. Although exercise-induced ST depression of up to 1 mm did not predict outcome significantly, a positive exercise RVG did predict cardiac events: 17% of patients with a positive test had an event, compared with 6% of those with a normal study (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous transluminal coronary angioplasty in evolving acute myocardial infarction

In 29 patients with evolving acute myocardial infarction, acute reperfusion of the infarct-related coronary artery was attempted using percutaneous transluminal coronary angioplasty (PICA). Before PTCA, angiography showed 23 totally occluded and 6 severely stenotic infarct-related coronary arteries. PTCA was initially successful in 25 of 29 patients (86%). Reocclusion occurred in 4 patients within 12 hours after successful PTCA and was associated with new electrocardiographic changes or recurrence of symptoms. In 17 patients the infarct-related coronary artery remained patent at early follow-up; late stenosis occurred in 4 patients. Recurrence of stenosis was accompanied by development of angina. No clinical or angiographic features distinguished those with ultimate vessel patency, occlusion or recurrence of stenosis. On follow-up, ventricular function appeared better preserved or improved in those with a patent infarct-related coronary artery than in those with an occluded infarct-related coronary artery. Further studies are warranted to compare PTCA and streptokinase as primary reperfusion modalities in evolving acute myocardial infarction.