Variants of renin-angiotensin system genes and echocardiographic left ventricular mass

Aims Variants of renin–angiotensin system genes are shown tobe associated with cardiovascular pathology. The associationbetween renin–angiotensin system genes and left ventricularmass was investigated in a population-based case-control study. Methods and Results The association between echocardiographic left ventricular massand both insertion/deletion polymorphism of the angiotensin-convertingenzyme gene and the methionine|adthreonine variant at position235 of the angiotensinogen gene was studied in a random cohortof 430 hypertensive and 426 control subjects. No differencesin the adjusted left ventricular mass values between the differentgenotypes were seen among either the hypertensive or the controlsubjects, whether men or women, or in the subgroups of normotensiveor physically active subjects. Gene variation had no statisticallysignificant synergistic effect on left ventricular mass values.In control women, the deletion allele of the angiotensin-convertingenzyme gene was associated with an increased risk of left ventricularhypertrophy. However, this finding was based on a small numberof women with left ventricular hypertrophy and should be interpretedwith caution. Conclusion Variations in renin–angiotensin system genes had no majoreffect on left ventricular mass in this middle-aged population-basedcohort of hypertensives and control subjects.     

The aging heart and post-infarction left ventricular remodeling

Aging is a risk factor for heart failure, which is a leading cause of death world-wide. Elderly patients are more likely than young patients to experience a myocardial infarction (MI) and are more likely to develop heart failure following MI. The poor clinical outcome of aging in cardiovascular disease is recapitulated on the cellular level. Increase in stress exposure and shifts in signaling pathways with age change the biology of cardiomyocytes. The progressive accumulation of metabolic waste and damaged organelles in cardiomyocytes blocks the intracellular recycling process of autophagy and increases the cell's propensity toward apoptosis. Additionally, the decreased cardiomyocyte renewal capacity in the elderly, due to reduction in cellular division and impaired stem cell function, leads to further cardiac dysfunction and maladaptive responses to disease or stress. We review the cellular and molecular aspects of post-infarction remodeling in the aged heart, and relate them to the clinical problem of post-infarction remodeling in elderly patients.     

Surgical left ventricular remodeling in heart failure

The high mortality and morbidity of patients in terminal heart failure are a therapeutic challenge to modern medicine. Surgically, cardiac transplantation is an excellent treatment for many patients. However, lack of donors combined with an increasing number of patients has led to the search for other surgical strategies. Patients with symptomatic large left ventricular aneurysms have been treated with resection of the aneurysm and closure of the left ventricle either directly (linear closure, first reported by Cooley) or by implantation of a patch (endoventricular patch plasty or Dor procedure). Akinetic areas of the left ventricle have also been successfully treated by the latter method. According to the law of Laplace, large dilated ventricles have increased wall tension and thus increased oxygen consumption. Based on this fact, Batista and coworkers have reduced the volume of enlarged left ventricles in patients in terminal heart failure by removing a wedge of myocardium from the apex of the heart towards the base of the left ventricular free wall. Although a favorable outcome has been reported in selected patients, this method is currently not recommended for treatment of heart failure because of high surgical failure rates. The present paper reviews some of the relevant literature regarding surgical left ventricular remodeling in heart failure. Two new techniques (Myosplint and CorCap cardiac support device) are also briefly described.     

Cell therapy for left ventricular remodeling

The increasing longevity of patients with heart failure (HF) and the rise in the incidence of HF has created an urgent need to effectively treat and prevent left ventricular remodeling. Within the past 6 years, skeletal myoblast and bone marrow mononuclear cell transplantation have been undertaken in over 200 patients with HF, geared to the underlying injury, not just its mechanisms. Early safety/feasibility studies showed promising but somewhat conflicting secondary symptomatic and functional improvements, and safety concerns have arisen. However, the patient population, cell type, dose, time, mode of delivery, and outcome measures differed—making comparisons problematic. It is now time to: 1) create a central registry of all patients treated with cells; 2) perform side-by-side comparisons of different types of cells in patients with similar HF states; 3) agree on standardized trial designs; and 4) define acceptable and unacceptable outcomes (and measures) compared with both standard of care and to other emerging therapies. By doing so, we can avoid the pitfalls that previous biologics (eg, angiogenic gene therapy) have suffered, increase the likelihood of success, shorten the time-to-presentation of cell-based algorithms to clinicians, and deliver these therapies to patients who await new ways of reduction of symptoms and improvement of quality of life.     

Apoptosis and post-infarction left ventricular remodeling

Apoptosis is a common pathological feature in acute myocardial infarction (AMI), however, its role in the later phases (>10 days) of AMI and in post-infarction left ventricular remodeling has not been characterized. The aim of the study was to identify signs of ongoing cell apoptosis late post AMI. Sixteen hearts were collected at autopsy from subjects 12 to 62 days after the onset of AMI. In situ end-labeling of DNA fragmentation (TUNEL) and co-staining with caspase-3 were performed. Double-positive cells were defined as apoptotic and the apoptotic rate was calculated. Values are expressed as median and interquartile range. Co-stainings with muscle-actin, splicing factor (SC35), PCNA, bax and bcl-2 were also performed. Apoptotic rates at site of infarction [25.4% (17.0-28.4%)] were significantly higher v those at remote regions [0.7% (0.5-0.8%) P<0.001] and significantly correlated to left ventricular longitudinal and transverse diameters [ r = +0.70 (P=0.016) and r = +0.63 (P=0.004) respectively]. Moreover, in subjects with persistently occluded infarct-related artery (14 cases) there was a significantly higher apoptotic rate at the site of infarction compared to those (2 cases) with patent artery [26.0% (21.9-28.5%) v 4.5% (0.6% and 8,4%);P=0.033]. A significantly greater bax immuno-reactivity close to the infarction v remote areas was found (P<0.001). High grade apoptosis is present at sites of infarction in the later phases post AMI. This is more evident if the infarct-related artery is persistently occluded and signs of ventricular remodeling are present. These data may provide an explanation of progressive late left ventricular dysfunction.     

Gender differences in postinfarction left ventricular remodeling.

OBJECTIVE: Previous studies suggest that gender affects the adaptive responses of the heart to some forms of cardiac overload. It is unknown whether gender influences left ventricular (LV) remodeling after myocardial infarction (MI). METHODS: We performed transthoracic echocardiographic-Doppler examinations in age-matched male (n = 17) and female (n = 16) rats before, and 1 and 6 weeks after transmural MI or sham surgery. RESULTS: Following large MI (male = 45 +/- 1% LV circumference vs. female = 48 +/- 4%, p = NS), both male and female rats developed progressive LV dilatation. Infarctions caused a similar degree of global and regional LV systolic dysfunction in males and females. Male rats had significant increases in the thickness of the noninfarcted posterior wall by 6 weeks after MI. However, posterior wall thickness did not change in the infarcted female rats. Average myocyte diameter in the noninfarcted region of the heart was also greater in male than female MI rats. The combination of increased cavity size with little change in wall thickness resulted in a greater decline in relative wall thickness in the female rats compared to the males. Male rats with MI showed progressively restricted LV diastolic filling as assessed by transmitral Doppler recordings. Female rats had less of an increase in the ratio of early to late transmitral velocities and less of an increase in the E wave deceleration rate after MI. CONCLUSIONS: Female rats showed a different pattern of LV remodeling than males with less of an increase in thickness of the noninfarcted portions of the left ventricle than males, but comparable LV cavity enlargement and systolic dysfunction. Despite similar infarct size, females developed less pronounced abnormalities of LV diastolic filling. We hypothesize that the gender-related differences in postinfarction LV remodeling may contribute to the different LV filling patterns, and might ultimately relate to differences in clinical outcome.     

Progressive left ventricular remodeling in patients with hypertrophic cardiomyopathy and severe left ventricular hypertrophy

OBJECTIVES: The aim of this study was to determine the natural history of patients with hypertrophic cardiomyopathy (HCM) and severe left ventricular hypertrophy (LVH) (i.e., maximal left ventricular wall thickness [MLVWT] >/=30 mm) and whether changes in cardiac morphology influence the course of the disease. BACKGROUND: Severe LVH is common in young and rare among elderly patients with HCM. This has been explained by a high incidence of sudden death. We hypothesized that this age-related difference might be explained by left ventricular wall thinning. METHODS: A total of 106 (age 33 +/- 15 years; 71 males) consecutive patients with severe LVH underwent history taking, examination, electrocardiography, echocardiography, cardiopulmonary exercise testing, and Holter analysis. Survival data were collected at subsequent clinic visits or by communication with patients and their general practioners. In order to assess morphologic and functional changes, 71 (67.0%) patients (mean age 31 +/- 15 years; 47 males) followed at our institution underwent serial (>/=1 year) assessment. RESULTS: Of the 106 patients, the majority (78 [71.6%]) were <40 years of age. During follow-up (92 +/- 50 months [range 1 to 169]), 18 (17.0%) patients died or underwent heart transplantation (13 sudden cardiac deaths, 2 heart failure deaths, 1 heart transplantation, 1 stroke, 1 postoperative death). Five-year survival from sudden death was 90.1% (95% confidence interval [CI] 84.0% to 96.3%), and that from heart failure death or transplantation was 97.7% (95% CI 94.5 to 100). In patients serially evaluated over 85 +/- 51 months, there was an overall reduction in MLVWT of 0.6 mm/year (95% CI 0.31 to 0.81, p = 0.00004). Wall thinning >/=5 mm was observed in 41 patients (57.7%; age 35 +/- 13 years; 28 males). On multivariate analysis, the follow-up duration only predicted wall thinning (0.6 mm/year, 95% CI 0.38 to 0.85, p < 0.00001). CONCLUSIONS: Left ventricular remodeling is common in patients with severe LVH and contributes to the low prevalence of severe LVH seen in middle age and beyond.     

Postinfarction left ventricular remodeling in patients with hypertension

1-3 years after myocardial infarction 140 patients (66 with - group 1, and 74 without - group 2 - hypertension before infarction) were examined by echocardiography. In group 1 concentric remodeling was found in 71.4% of patients with postinfarction scar occupying 相似文献   

Surgical methods to reverse left ventricular remodeling

Heart transplantation remains the gold standard treatment for “end-stage” dilated cardiomyopathy. However, its epidemiologic impact on the heart failure problem continues to be small due to limited donor organ availability and contraindications. Therefore, several “conventional” surgical procedures have been developed to reverse the vicious cycle of ventricular remodeling that accompanies systolic heart failure and to improve symptoms and survival of the patients. This review discusses indications, results, and limitations of the most common surgical methods currently used to arrest or reverse cardiac remodeling.     

性别对心脏重构的影响

性激素对于生殖系统以外众多系统的作用越来越受到重视,尤其是心血管系统。近来研究发现,性别对心脏重构有着微妙而独特的影响。女性和男性针对损伤所产生的心脏重构反应存在重要差别。这些差别与性激素(如:雌激素)的关系密不可分,雌激素和睾酮对心脏重构的分子效应迄今尚未充分阐明,可能与肾素-血管紧张素系统、心肌细胞凋亡、雌激素受体介导的炎症免疫反应的调控等有关。该文就性激素对心脏重构影响的机制作一综述。     

急性心肌梗死与左室重构

急性心肌梗死(AMI)后左室发生细胞学,分子学及细胞间质的变化,进而引起左室在大小、形态、组织结构和功能状态的改变,此即目前许多研究所提及的AMI后的左室重构.AMI后左室的重构贯穿于整个病程的始终,成为影响AMI患者近远期预后的主要原因之一.     

老龄性心室重构过程

老龄是心力衰竭最主要的危险因素之一.与年轻者相比,老龄性心脏重构的分子基础包括心肌细胞凋亡、自噬、更新失效等更明显.细胞凋亡可以通过内在的或者外在的途径进行调节.与这些途经相关的许多因素都随年龄的增长而增加.自噬是心肌细胞生存必不可少的过程.心肌细胞肥大和心肌间质纤维化作为老龄化心脏心肌细胞数量减少的代偿机制,被认为是...     

ECG manifestations of left ventricular electrical remodeling

Research and thinking about the electrocardiographic manifestations of left ventricular hypertrophy has been constrained by a limited conceptual model of the process: heart disease produces chamber enlargement (increased mass), which in turn produces an altered electrocardiogram. The process is much more complex than can be represented in this simple model. A more robust and intricate model is proposed, in which heart (and vascular) disease causes structural changes, electrical changes, biochemical changes, and others, all of which interact to produce electrical remodeling of ventricular myocardium. This electrical remodeling results in a variety of ECG changes. All of these changes interact, leading to an altered clinical course, and to premature death. It is suggested that research, based on this model, can provide new clues to the processes involved, and improve the prediction of clinical outcomes. New directions in research, in recording equipment, and in organizational activities are suggested to test this new model, and to improve the usefulness of the electrocardiogram as a research and diagnostic tool.     

Central vasopressin is modulated by chronic blockade of the renin-angiotensin system in experimental left ventricular hypertrophy

We studied the interaction of the central renin-angiotensin system (RAS) and vasopressin system in rats with left ventricular hypertrophy (LVH) due to aortic banding. In these animals plasma vasopressin is elevated and vasopressin content is increased in specific brain areas. Chronic blockade of the RAS by angiotensin-converting enzyme (ACE) inhibition (ramipril) and AT1 receptor antagonism (losartan) significantly attenuated circulating and central vasopressin in rats with LVH. Given the antidiuretic, vasoconstrictive, and growth-promoting effects, vasopressin may participate in the cardiovascular alterations in LVH. Blockade of the RAS strongly ameliorates central and peripheral-vasopressin. Therefore, central modulatory effects on vasopressin might contribute to the therapeutic efficacy of ACE inhibitors and AT1 antagonists.     

Left ventricular hypertrophy and renin-angiotensin system blockade

The renin-angiotensin system (RAS), an important control system for blood pressure and intravascular volume, also causes left ventricular hypertrophy (LVH) and fibrosis. The main causal mechanism is the increase in blood pressure, which leads to increased left ventricular wall stress; however, aldosterone release from the adrenals and (more controversially) the direct action of angiotensin II on the cardiomyocytes also play a role. Large clinical trials evaluating the blockade of the RAS with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers have demonstrated an ability to prevent progression and induce regression of left ventricular mass, thereby reducing the significant and independent cardiovascular risk conferred by LVH. Regression of left ventricular mass is also achieved by other medication classes, but the RAS blockers have an additional beneficial effect for the same blood pressure reduction, for which the mechanism is not entirely clear. Studies comparing the efficacy of angiotensin-converting enzyme inhibitors versus angiotensin receptor blockers to achieve LVH regression have not demonstrated any clear benefit of one class over the other.