Management Of Myocardial Ischemia Research Articles

ПОЛОВОЙ ДИМОРФИЗМ КЛИНИЧЕСКИХ И ЭЛЕКТРОКАРДИОГРАФИЧЕСКИХ ИЗМЕНЕНИЙ У БОЛЬНЫХ БЕЗБОЛЕВОЙ ИШЕМИЕЙ МИОКАРДА 3 ТИПА

Безболевая ишемия миокарда у больных сахарным диабетом 2-го типа является довольно распространенным явлением, поскольку ее частота колеблется от 15 до 64,7%. Цель исследования заключалась в анализе полового диморфизма клинических и электрокардиографических проявлений у представителей разного пола. Для достижения цели исследования проведен комплекс клинических и инструментальных исследований морфофункционального состояния сердца. В результате проведенных исследований установлено, что половой диморфизм безболевой ишемии миокарда у мужчин появлялся вначале дебютом приступов болевой стенокардии, у женщин, напротив, болевые приступы стенокардии во времени следовали за безболевой ишемией. У мужчин безболевая ишемия сопровождалась классической иррадиацией стенокардической боли в левую руку, челюсть и межлопаточное пространство, ощущением перебоев в деятельности сердца. У женщин безболевая ишемия миокарда сопровождалась сердцебиением, одышкой или отсутствием кардиальных жалоб. Половой диморфизм ЭКГ-признаков проявлялся в виде преобладания у мужчин желудочковой экстрасистолии и гипертрофии/перегрузки левых отделов сердца. У женщин с безболевой ишемией на ЭКГ в отличие от мужчин преобладали синусовая аритмия и суправентрикулярная экстрасистолия.

HIF-1α Preconditioning Potentiates Antioxidant Activity in Ischemic Injury: The Role of Sequential Administration of Dihydrotanshinone I and Protocatechuic Aldehyde in Cardioprotection.

Aims: The management of myocardial ischemia has been challenged by reperfusion injury. Reactive oxygen species (ROS) production is the critical cause of reperfusion injury, but antioxidant treatment failed to gain satisfactory effects. We hypothesized that improvement of redox homeostasis by preconditioning regulation should potentiate the ability of antioxidants to protect the heart from reperfusion injury. Results: By phenotype-based screening, we identified that dihydrotanshinone I (DT) and protocatechuic aldehyde (PCA) potently protected cardiomyocytes through preconditioning regulation and antioxidant activity, respectively. DT induced transient ROS generation via reversible inhibition of mitochondrial respiratory complex I and thereby stabilizing HIF-1α, while PCA elevated the levels of reduced glutathione (GSH) by providing reducing equivalents to scavenge ROS. HIF-1α, stabilized by DT, transcriptionally upregulated Nrf2 and thereby activated antioxidant enzymes, potentiating PCA to protect cardiomyocytes from reperfusion injury by strengthening intrinsic ROS scavenging capacity. In rat ischemia/reperfusion (I/R) model, sequential administration of DT and PCA, but not in reverse, additively protected the heart from I/R injury, manifested by reduced infarct size and improved cardiac function. These results were further supported by sequential administration of metformin and vitamin E in the rat and porcine I/R models. Innovation and Conclusion: Our work demonstrates that preconditioning regulation of redox state is essential for antioxidants to protect the heart from I/R injury, providing a new direction for the treatment of myocardial injury.

Does gender influence the outcome of ischemic heart disease?

Diseases of the cardiovascular system (myocardial infarction, stroke, heart failure, hypertensive heart disease, cardiomyopathy) account for 40% of all deaths in men and up to 49% of all deaths in women. For a long time it was thought that the clinical picture of ischemic heart disease in men and women was similar. Now, however, there are more reports suggesting that diverse manifestations of the symptoms of ischemic disease may be related to differences between sexes.The disparity between women and men is also evident in the diagnostic process, and various pathological mechanisms of cardiovascular diseases, in particular myocardial ischemia in men and women, affect the differences in the results of diagnostic tests. Vasomotor dysfunction is particularly frequent in women, as their coronary vessels are more sensitive to the catecholamines released during mental stress, resulting in spasm and ischemic myocardium. Moreover, a much lower dose of acetylcholine induced vasoconstriction, which indicates that women are more sensitive to this neurotransmitter. Therefore, coronary vasomotor disorders in the form of epicardial and microvascular dysfunction are more often seen in women. All these mentioned factors resulted in higher mortality and poorer quality of life of women suffering from ischemic heart disease.

The prevalence of electrocardiographic abnormalities in the Russian population in the early 21st century (the ESSE-RF study)

Electrocardiography (ECG) takes the lead in assessing the prevalence of coronary artery disease (CAD) in the population. ECG disorders, grouped in the Major (certain) and Minor (possible) categories, are prognostic markers of a high risk of cardiovascular diseases and sudden cardiac death. Unified assessing methods of ECG disorders prevalence and their associations with socio-demographic parameters have not previously been made in Russia.Aim. To study the prevalence of ECG parameters of certain and possible coronary artery disease among population of Russia, depending on the socio-demographic characteristics — age, sex, education and place of residence (city or country).Material and methods. We used 17504 ECGs from representative samples of population (25-64 years old), who participated in the epidemiological study “Epidemiology of cardiovascular diseases and their risk factors in the Russian Federation”. The analysis using Minnesota code was carried out among men and women of four age groups, two educational levels, among citizens and countrymen.Results. The highest prevalence was observed in the “Certain” (5,7%) and “Possible signs of CAD” (7,1%) categories, in the “Certain” (3,8%) and “Possible myocardial ischemia” groups (4,9%), the smallest is in the “Rhythm and conduction disorder” (0,7%) and “STT changes in left ventricular hypertrophy” (0,4%) groups. It was shown that the frequency of ECG disorders increases with age, has an sharp increase after 55 years, regardless of sex. In the age dynamics of categories, STT changes and atrial fibrillation have a decrease of gender differences. All groups of ECG disorders are detected more often among men than women, except for STT changes. With an increase in the level of education, the frequency of ECG pathologies decreases, with the exception of the groups of “major” and “minor Q (QS)”, “major rhythm and conduction disorders”. The prevalence of most ECG disorders does not depend on the place of residence. However, signs of major myocardial ischemia in men are more common in country than in the city (3,9% vs. 2,7%, p<0,05).Conclusion. The results confirm the patterns identified earlier. There is a steady association of ECG data with socio-demographic characteristics.

Associations of the serum long-chain omega-3 polyunsaturated fatty acids and hair mercury with exercise-induced myocardial ischemia in men: The kuopio ischaemic heart disease risk factor study

Rationale: Long-chain omega-3 polyunsaturated fatty acids (PUFA) from fish is associated with lower risk of coronary heart disease (CHD). Fish may also contain methylmercury, which is associated with higher CHD risk. However, mechanisms underlying these associations are not fully known. We investigated the association of serum long-chain omega-3 PUFA and hair mercury concentrations with the odds for myocardial ischemia during exercise, a predictor of future cardiac events.

Estimation of the Blood Pressure Response With Exercise Stress Testing

The blood pressure response to exercise has been described as a significant increase in systolic BP (sBP) with a smaller change in diastolic BP (dBP). This has been documented in small numbers, in healthy young men or in ethnic populations. This study examines these changes in low to intermediate risk of myocardial ischaemia in men and women over a wide age range. Consecutive patients having stress echocardiography were analysed. Ischaemic tests were excluded. Manual BP was estimated before and during standard Bruce protocol treadmill testing. Patient age, sex, body mass index (BMI), and resting and peak exercise BP were recorded. 3,200 patients (mean age 58±12years) were included with 1,123 (35%) females, and 2,077 males, age range 18 to 93 years. Systolic BP increased from 125±17mmHg to 176±23mmHg. The change in sBP (ΔsBP) was 51mmHg (95% CI 51,52). The ΔdBP was 1mmHg (95% CI 1, 1), from 77 to 78mmHg, p<0.001). The upper limit of normal peak exercise sBP (determined by the 90th percentile) was 210mmHg in males and 200mmHg in females. The upper limit of normal ΔsBP was 80mmHg in males and 70mmHg in females. The lower limit of normal ΔsBP was 30mmHg in males and 20mmHg in females. In this large cohort, sBP increased significantly with exercise. Males had on average higher values than females. Similar changes were seen with the ΔsBP. The upper limit of normal for peak exercise sBP and ΔsBP are reported by age and gender.

Noninvasive approach to mend the broken heart: Is "remote conditioning" a promising strategy for application in humans?

Currently, there are no satisfactory interventions to protect the heart against the detrimental effects of ischemia-reperfusion injury. Although ischemic preconditioning (PC) is the most powerful form of intrinsic cardioprotection, its application in humans is limited to planned interventions, due to its short duration and technical requirements. However, many organs/tissues are capable of producing "remote" PC (RPC) when subjected to brief bouts of ischemia-reperfusion. RPC was first described in the heart where brief ischemia in one territory led to protection in other area. Later on, RPC started to be used in patients with acute myocardial infarction, albeit with ambiguous results. It is hypothesized that the connection between the signal triggered in remote organ and protection induced in the heart can be mediated by humoral and neural pathways, as well as via systemic response to short sublethal ischemia. However, although RPC has a potentially important clinical role, our understanding of the mechanistic pathways linking the local stimulus to the remote organ remains incomplete. Nevertheless, RPC appears as a cost-effective and easily performed intervention. Elucidation of protective mechanisms activated in the remote organ may have therapeutic and diagnostic implications in the management of myocardial ischemia and lead to development of pharmacological RPC mimetics.

Testosterone and the Heart.

Testosterone (T) has a number of important effects on the cardiovascular system. In men, T levels begin to decrease after age 40, and this decrease has been associated with an increase in all-cause mortality and cardiovascular (CV) risk. Low T levels in men may increase their risk of developing coronary artery disease (CAD), metabolic syndrome, and type 2 diabetes. Reduced T levels in men with congestive heart failure (CHF) portends a poor prognosis and is associated with increased mortality. Studies have reported a reduced CV risk with higher endogenous T concentration, improvement of known CV risk factors with T therapy, and reduced mortality in T-deficient men who underwent T replacement therapy versus untreated men. Testosterone replacement therapy (TRT) has been shown to improve myocardial ischemia in men with CAD, improve exercise capacity in patients with CHF, and improve serum glucose levels, HbA1c, and insulin resistance in men with diabetes and prediabetes. There are no large long-term, placebo-controlled, randomized clinical trials to provide definitive conclusions about TRT and CV risk. However, there currently is no credible evidence that T therapy increases CV risk and substantial evidence that it does not. In fact, existing data suggests that T therapy may offer CV benefits to men.

Remote preconditioning as a novel "conditioning" approach to repair the broken heart: potential mechanisms and clinical applications.

Remote ischemic preconditioning (RIPC) is a novel strategy of protection against ischemia-reperfusion (IR) injury in the heart (and/or other organs) by brief episodes of non-lethal IR in a distant organ/tissue. Importantly, RIPC can be induced noninvasively by limitation of blood flow in the extremity implying the applicability of this method in clinical situations. RIPC (and its delayed phase) is a form of relatively short-term adaptation to ischemia, similar to ischemic PC, and likely they both share triggering mechanisms, whereas mediators and end-effectors may differ. It is hypothesized that communication between the signals triggered in the remote organs and protection in the target organ may be mediated through substances released from the preconditioned organ and transported via the circulation (humoral pathways), by neural pathways and/or via systemic anti-inflammatory and antiapoptotic response to short ischemic bouts. Identification of molecules involved in RIPC cascades may have therapeutic and diagnostic implications in the management of myocardial ischemia. Elucidation of the mechanisms of endogenous cardioprotection triggered in the remote organ could lead to the development of diverse pharmacological RIPC mimetics. In the present article, the authors provide a short overview of RIPC-induced protection, proposed underlying mechanisms and factors modulating RIPC as a promising cardioprotective strategy.

Relationship between the ischemic ST-T changes in ECG and the coronary artery diseases

To analyze the relationship between the ischemic ST-T changes in electrocardiogram (ECG) and the coronary artery diseases based on the perspective of diagnostics. A total of 341 patients, who underwent coronary angiography in Department of Cardiology of Xiangya Hospital, Central South University from June 2013 to April 2014, were enrolled for this study. The internationally recognized diagnostic criteria for ischemic ST-T changes in ECG and the Judkins diagnostic criteria for coronary angiography were applied, respectively. The sensitivity and specificity of ECG were analyzed. There were more ischemic ST-T changes in women than that in men (P<0.01). Ischemic changes in coronary angiography were not significantly different between male and female patients (P>0.05). For ischemic diagnostic tests by ECG ST-T, the total sensitivity and specificity was 83.6% and 54.4%, respectively. The sensitivity and specificity was 82.3% and 68.0% or 85.0% and 28.2% in the male or female group, respectively. Ischemic ST-T changes in ECG possess important value in the diagnosis of the coronary artery diseases. The sensitivity of ECG in the diagnosis of myocardial ischemia in women was higher than that in men, whereas the specificity of ECG in the diagnosis of myocardial ischemia in men was higher than that in women.

Gender Difference in Albuminuria and Ischemic Heart Disease in Type 2 Diabetes

The value of urinary albumin excretion in the prediction of myocardial ischemia in men and women with type 2 diabetes is not well understood. We questioned whether gender influences the albuminuria-ischemic heart disease relationship in patients with type 2 diabetes. We designed a matched case-control study of 926 patients with albuminuria (cases) and 926 age and body mass index matched patients without albuminuria (controls). Ischemic heart disease was defined as the presence of (1) history of angina pectoris or angina equivalent symptoms and critical care unit admission, (2) myocardial infarction and/or electrocardiographic evidence of Q-wave myocardial infarction, (3) coronary revascularization and/or stenting, (4) positive myocardial single-photon emission computed tomography scan, (5) ischemic ST-segment or T-wave changes, and (6) positive stress testing. Patients with albuminuria had a lower glomerular filtration rate and a longer diabetes duration than patients without albuminuria. In the group of cases, there were a greater number of men with ischemic heart disease (120 of 370; 32.4%) compared to women (97 of 559; 17.4%) (P<0.001). The odds ratio of having ischemic heart disease according to the presence or absence of albuminuria was 1.25 [95% CI: 1.01-1.56] (P<0.05) in all studied populations, 0.79 [95% CI: 0.51-1.21] (P=0.14) in women, and 2.84 [95% CI: 1.68-4.79] (P<0.001) in men. We showed that diabetes duration, high-density lipoprotein, low-density lipoprotein, and hemoglobin A(1c) influence albuminuria in women, while diabetes duration, fasting blood sugar, and diastolic blood pressure influence albuminuria in men. Men with albuminuria are at increased risk of ischemic heart disease compared to women. This may be related to the role of high-density lipoprotein on the albuminuria-gender relationship.

Meta-Analysis of B-Type Natriuretic Peptide's Ability to Identify Stress Induced Myocardial Ischemia

Studies in victims of sudden cardiac death and those surviving a cardiac arrest have confirmed that extent of coronary artery disease is similar in those with and without angina, suggesting that it is the presence of myocardial ischemia rather than associated symptoms that determine the prognosis. Experimental models show that hypoxic myocardial tissue results in production of extra B-type natriuretic peptide (BNP), suggesting that BNP could potentially serve as a biomarker of myocardial ischemia. We performed a meta-analysis of the studies that link BNP to inducible myocardial ischemia as indicated by noninvasive stress tests. Values of true positive, false positive, true negative, and false negative were calculated from the reported sensitivity, specificity, disease prevalence, and total number of patients studied. Sixteen studies reporting data on 2,784 patients across 14 study populations were included in the final analysis. Mean age of participants was 55 to 69 years and 55% to 90% were men. Pooled sensitivity and specificity of BNP for detection of stress-induced myocardial ischemia were 71% (95% confidence interval [CI] 68 to 74) and 52% (95% CI 52 to 54), respectively. Pooled diagnostic odds ratio was 3.5 (95% CI 2.46 to 5.04) and summary receiver operating characteristic curve revealed an area under the curve of 0.71 ± 0.02 (mean ± SE). In conclusion, this meta-analysis suggests that an increased BNP level can identify inducible ischemia as detected by standard noninvasive stress tests. This raises the possibility of a whole new role for BNP in the diagnosis and management of myocardial ischemia.

Echocardiographic analysis with a two-dimensional strain of chronic myocardial ischemia induced with ameroid constrictor in the pig

Despite much progress in the medical management of myocardial ischemia, several problems remain and experimental models help to improve our understanding of the pathophysiology involved in this domain. The ameroid constrictor model is the most widely used to create ischemia but evaluation of patent ischemia is still under debate. In the present study, we describe the potential of a two-dimensional (2D) strain for experimentally evaluating myocardial ischemia in the pig. An ameroid constrictor was placed around the circumflex artery in 30 pigs. Angiography showed 90% stenosis at one and two months. Left ventricular function was moderately altered and associated with mitral valve insufficiency in 30% of cases. Longitudinal and circumference strains were dramatically modified in the ischemic inferior-lateral zone compared to the healthy anterior zone (P<0.01) at one and two months. We correlated these results to myocardial ischemia by using contrast echocardiography, which showed a significant reduction in myocardial perfusion in the ischemic zone compared to the uninjured area, and by using histological analysis. We showed that evaluation of the 2D strain could be an interesting approach for assessing myocardial ischemia after ameroid constrictor implantation. The 2D strain represents a useful tool for the evaluation of experimental models of myocardial ischemia.

Myocardial Bridging

According to postmortem studies, coronary atherosclerosis can be substantial and reach a high prevalence of advanced lesions, including atheroma and fibroatheroma in young adults.1,2 Risk factors associated with coronary atherosclerosis such as dyslipidemia, smoking, diabetes mellitus, and hypertension have been identified. The development of atherosclerosis seems to be related to the magnitude and duration of exposure.3 Although research concentrates on identifying genetic markers in genome-wide association studies, there is still a lack of knowledge about the individual risk of developing coronary atherosclerosis.4 When atherosclerosis presents as acute coronary syndromes, mortality may be high.5 Plaque rupture and erosion have been identified as major underlying pathological-anatomic characteristics,6 but some suspect other mechanisms.7 In this issue of Circulation , Ishikawa et al8 present evidence that myocardial bridging may play a role as a congenital anatomic risk factor for coronary atherosclerosis and myocardial infarction. Article see p 376 Myocardial bridging results when myocardial tissue covers part of the left anterior descending coronary artery, resulting in a tunneled arterial segment, which can be regarded as a congenital variant.9–11 The prevalence is reported to be >50% at autopsy.12 Clinically, the diagnosis of myocardial bridging is established by coronary angiography demonstrating a systolic compression, described as a “milking effect,”13 but it was present in only <5% of cases recently in a large number of Chinese patients.14 When nitroglycerin was used as …

The Effect of High Dose Melatonin on Cardiac Ischemia-reperfusion Injury

PurposeMelatonin, the most potent scavenger of toxic free radicals, has been found to be effective in protecting against pathological states due to the release of reactive oxygen species. This study was performed to establish the effect of high dose melatonin on protection against ischemia-reperfusion (I/R) injury in rat hearts.Materials and MethodsForty male Sprague-Dawley rats were used in this study. They were separated into four groups of ten rats each. A left coronary artery occlusion was induced in the rats by ligating the artery for 20 minutes and then releasing the ligation (reperfusion) afterwards. The control group was Group A. Group B was subjected to myocardial ischemia-reperfusion without any treatment, while Group C underwent myocardial ischemia-reperfusion with a melatonin treatment before the ischemia. Group D was subjected to myocardial ischemia-reperfusion with a melatonin treatment before the reperfusion. After 20 minutes of reperfusion, blood samples were obtained from each group for biochemical studies, and the animals were sacrificed for histological and, immunohistochemical examinations of the myocardial tissue.ResultsWe found that the cardiac troponin T(cTn-T) levels were significantly increased in Group B when all groups were compared. In the Group C rats treated with melatonin, the cTn-T values were significantly lower than those in Groups B and D. In addition, malondialdehyde (MDA) and antioxidant enzymes including, superoxide dismutase (SOD) and myeloperoxidase (MPO) were lower than those in Group B in the melatonin treated groups. The differences were statistically significant (p < 0.05). Histopathologic and immunohistopathologic studies also supported the effectiveness of melatonin.ConclusionOur study suggests that high dose melatonin, appears to offer protection against cardiac ischemia-reperfusion injuries in rats by scavenging the free radicals and could have a potential clinical use in the management of myocardial ischemia.

Androgen Deficiency as a Predictor of Metabolic Syndrome in Aging Men

The prevalence of metabolic syndrome is increasing globally and is an important risk factor for the development of cardiovascular disease. Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid and aortic atherosclerosis. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity, insulin sensitivity, glycaemic control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. The effect of testosterone therapy on atherogenesis in men is unknown; however, animal studies have shown that testosterone is atheroprotective and can ameliorate the degree of atherosclerosis. Testosterone is an arterial vasodilator and has been shown to improve myocardial ischaemia in men with coronary artery disease. This review discusses the role that testosterone may play in the pathogenesis of metabolic syndrome in men and also examines the potential role of testosterone replacement therapy in this condition.

Effects of Oral Testosterone Treatment on Myocardial Perfusion and Vascular Function in Men With Low Plasma Testosterone and Coronary Heart Disease

Intracoronary testosterone infusions induce coronary vasodilatation and increase coronary blood flow. Longer term testosterone supplementation favorably affected signs of myocardial ischemia in men with low plasma testosterone and coronary heart disease. However, the effects on myocardial perfusion are unknown. Effects of longer term testosterone treatment on myocardial perfusion and vascular function were investigated in men with CHD and low plasma testosterone. Twenty-two men (mean age 57 ± 9 [SD] years) were randomly assigned to oral testosterone undecanoate (TU; 80 mg twice daily) or placebo in a crossover study design. After each 8-week period, subjects underwent at rest and adenosine-stress first-pass myocardial perfusion cardiovascular magnetic resonance, pulse-wave analysis, and endothelial function measurements using radial artery tonometry, blood sampling, anthropomorphic measurements, and quality-of-life assessment. Although no difference was found in global myocardial perfusion after TU compared with placebo, myocardium supplied by unobstructed coronary arteries showed increased perfusion (1.83 ± 0.9 vs 1.52 ± 0.65; p = 0.037). TU decreased basal radial and aortic augmentation indexes (p = 0.03 and p = 0.02, respectively), indicating decreased arterial stiffness, but there was no effect on endothelial function. TU significantly decreased high-density lipoprotein cholesterol and increased hip circumference, but had no effect on hemostatic factors, quality of life, and angina symptoms. In conclusion, oral TU had selective and modest enhancing effects on perfusion in myocardium supplied by unobstructed coronary arteries, in line with previous intracoronary findings. The TU-related decrease in basal arterial stiffness may partly explain previously shown effects of exogenous testosterone on signs of exercise-induced myocardial ischemia.

Inverse Relationship between Serum Levels of Interleukin-1β and Testosterone in Men with Stable Coronary Artery Disease

To examine the relationship between serum levels of inflammatory cytokines and testosterone in men with stable coronary artery disease (CAD). Evidence supports a beneficial effect of testosterone upon objective measures of myocardial ischaemia in men with CAD, and in animal models of atherosclerosis. Inflammatory cytokines are involved in many stages of the atherosclerotic process, however, the effect of testosterone upon inflammatory cytokines within the cardiovascular system is largely unknown. Serum was collected from 69 men (59+/-1 years) having >75% occlusion of 1, 2, or 3 coronary arteries. Levels of total testosterone (TT), bioavailable testosterone (BT), tumour necrosis factor-alpha (TNFalpha), interleukin (IL)-1-beta (IL-1beta), IL-6 and IL-10 were measured and analysis made between men with 1, 2, or 3 vessel CAD, and between men with hypogonadal, borderline hypogonadal and eugonadal serum levels of testosterone. In patients with 1, 2, or 3 vessel CAD, significant stepwise increases were observed in levels of IL-1beta: 0.16+/-0.03, 0.22+/-0.06, and 0.41+/-0.08 pg/ml (p=0.035), and IL-10: 0.93+/-0.11, 1.17+/-0.14, and 2.94+/-0.65 pg/ml (p=0.008). A significant stepwise increase in levels of IL-1beta was also observed in eugonadal, borderline hypogonadal, and hypogonadal men: 0.19+/-0.05, 0.29+/-0.05, and 0.46+/-0.13 pg/ml (p=0.047). Consequently this data implicates IL-1beta and IL-10 in the pathogenesis of CAD and suggests that testosterone may regulate IL-1beta activity in men with CAD.

Ivabradine: a Selective If Current Inhibitor in the Treatment of Stable Angina

The role of heart rate reduction in the management of myocardial ischemia and chronic stable angina is pivotal. However, broad use and appropriate dosing of commonly used rate-slowing drugs is limited by their poor tolerability. Ivabradine is a selective inhibitor of the If currents of the sinoatrial node cells. If currents activity determines the slope of the depolarization curve towards the threshold level controlling heart rate in patients with sinus rhythm. Ivabradine, a compound of the benzocyclobutane (S 16257), exhibits a unique specificity for the If current and has a more favorable profile of adverse reactions compared to other If inhibitors. Accordingly, ivabradine has been used in the treatment of stable angina, where it presented anti-anginal and anti-ischemic effects equivalent to the effects of atenolol and amlodipine. Clinical studies proved the efficacy of ivabradine in patients with stable angina, while clinical data are awaited to verify its probable value in the treatment of atrial tachyarrhythmias and tachycardia due to ventricular dysfunction. Thus, the clinical value of ivabradine, which has completed clinical development for stable angina, is expected to exceed its role in the treatment of myocardial ischemia. In this context, ivabradine, promising efficacious and safe pharmacological management of heart rate, is a huge step in cardiovascular therapeutics.

Do mechanical markers of myocardial ischaemia predict the transmural extent of myocardial infarction in man?

The present study aimed to explore the relationship between the transmural extent of myocardial necrosis and mechanical markers of myocardial ischaemia in man. A group of 40 patients with previous Q-wave myocardial infarction and a left ventricular ejection fraction (LVEF) of 27 +/- 11% was studied by cine and contrast-enhanced magnetic resonance imaging. Necrotic areas of delayed contrast enhancement were present in every patient and involved 20 +/- 8% of left ventricular myocardium. In involved segments, the transmural extent of contrast enhancement varied from 5% to 100%, being on average 38 +/- 25% of the wall thickness. End-diastolic left ventricular wall thickness and systolic wall thickening were lower in contrast-enhanced segments than in the other segments (P < 0.001). Furthermore, although left ventricular wall thickness and systolic wall thickening decreased as the transmural extent of contrast enhancement increased, the correlations were weak (r = -0.382 and -0.45, respectively). Finally, a delayed contrast enhancement was present in 89% of akinetic and in 94% of dyskinetic segments; however, contrast enhancement was also present in 18% of the segments with normal wall motion and in 56% of hypokinetic segments. Although mechanical markers of myocardial ischaemia substantially reflect the transmural extent of myocardial infarction, none of them can be considered as a substitute for the direct observation of necrotic tissue and its transmural extent, as provided by contrast-enhanced magnetic resonance imaging.