Mitral Valve Replacement and Remodeling of the Left Ventricle in Dilated Cardiomyopathy with Mitral Regurgitation: Initial Results

OBJECTIVE: This study evaluated the effects of a new method of mitral valve replacement on left ventricular (LV) remodeling and heart failure functional class. METHODS: Eight patients (6 men) with severe mitral regurgitation from end-stage dilated cardiomyopathy underwent surgery. Five patients were in functional class (FC) IV, 2 were in FC III and 1 was in FC III/IV. Age ranged from 33 to 63 years. Both the anterior and posterior leaflets of the mitral valve were divided into hemileaflets. The resultant 4 pedicles were displaced under traction toward the left atrium and anchored between the mitral annulus and an implanted valvular prosthesis. The beating heart facilitated ideal chordae tendineae positioning. RESULTS: All patients survived and were discharged from the hospital. After a mean follow-up period of 6.5 months (1-12 m), 5 patients were in FC I; 2 in FC I/II; and 1 in FC II. The preoperative ejection fraction ranged from 19% to 30% (mean: 25.7±3.4 %), and the postoperative ejection fraction ranged from 21% to 40% (mean: 31.1± 5.8%). Doppler echocardiography showed evidence of LV remodeling in 4 patients, including lateral wall changes and a tendency of the LV cavity to return to its elliptical shape. CONCLUSION: This technique of mitral valve replacement, involving new positioning of the chordae tendineae, allowed LV remodeling and improvement in FC during this brief follow-up period.

Correlations Between the Collagen Content of the Human Left Ventricular Myocardium, Measured by Biochemical and Morphometric Methods

OBJECTIVE: To assess, in myocardium specimens obtained from necropsies, the correlation between the concentration of hydroxyproline, measured with the photocolorimetric method, and the intensity of fibrosis, determined with the morphometric method. METHODS: Left ventricle myocardium samples were obtained from 45 patients who had undergone necropsy, some of them with a variety of cardiopathies and others without any heart disease. The concentrations of hydroxyproline were determined with the photocolorimetric method. In the histologic sections from each heart, the myocardial fibrosis was quantified by using a light microscope with an integrating ocular lens. RESULTS: A median of, respectively, 4.5 and 4.3 mug of hydroxyproline/mg of dry weight was found in fixed and nonfixed left ventricle myocardium fragments. A positive correlation occurred between the hydroxyproline concentrations and the intensity of fibrosis, both in the fixed (Sr=+0.25; p=0.099) and in the nonfixed (Sr=+0.32; p=0.03) specimens. CONCLUSION: The biochemical methodology was proven to be adequate, and manual morphometry was shown to have limitations that may interfere with the statistical significance of correlations for the estimate of fibrosis intensity in the human myocardium.

Subendocardial fibrosis in remote myocardium results from reduction of coronary driving pressure during acute infarction in rats

OBJECTIVE: To investigate the role of hemodynamic changes occurring during acute MI in subsequent fibrosis deposition within non-MI. METHODS: By using the rat model of MI, 3 groups of 7 rats each [sham, SMI (MI <30%), and LMI (MI >30%)] were compared. Systemic and left ventricular (LV) hemodynamics were recorded 10 minutes before and after coronary artery ligature. Collagen volume fraction (CVF) was calculated in picrosirius red-stained heart tissue sections 4 weeks later. RESULTS: Before surgery, all hemodynamic variables were comparable among groups. After surgery, LV end-diastolic pressure increased and coronary driving pressure decreased significantly in the LMI compared with the sham group. LV dP/dt max and dP/dt min of both the SMI and LMI groups were statistically different from those of the sham group. CVF within non-MI interventricular septum and right ventricle did not differ between each MI group and the sham group. Otherwise, subendocardial (SE) CVF was statistically greater in the LMI group. SE CVF correlated negatively with post-MI systemic blood pressure and coronary driving pressure, and positively with post-MI LV dP/dt min. Stepwise regression analysis identified post-MI coronary driving pressure as an independent predictor of SE CVF. CONCLUSION: LV remodeling in rats with MI is characterized by predominant SE collagen deposition in non-MI and results from a reduction in myocardial perfusion pressure occurring early on in the setting of MI.

Enalapril alters the formation of the collagen matrix in spontaneously hypertensive rats

OBJECTIVE: To assess the effect of the inhibition of the angiotensin-converting enzyme on the collagen matrix (CM) of the heart of newborn spontaneously hypertensive rats (SHR) during embryonic development. METHODS: The study comprised the 2 following groups of SHR (n=5 each): treated group - rats conceived from SHR females treated with enalapril maleate (15 mg. kg-1.day-1) during gestation; and nontreated group - offspring of nontreated females. The newborns were euthanized within the first 24 hours after birth and their hearts were removed and processed for histological study. Three fields per animal were considered for computer-assisted digital analysis and determination of the volume densities (Vv) of the nuclei and CM. The images were segmented with the aid of Image Pro Plus® 4.5.029 software (Media Cybernetics). RESULTS: No difference was observed between the treated and nontreated groups in regard to body mass, cardiac mass, and the relation between cardiac and body mass. A significant reduction in the Vv[matrix] and a concomitant increase in the Vv[nuclei] were observed in the treated group as compared with those in the nontreated group. CONCLUSION: The treatment with enalapril of hypertensive rats during pregnancy alters the collagen content and structure of the myocardium of newborns.

Gender-Based Differences in Cardiac Remodeling and ILK Expression after Myocardial Infarction

Background: Gender can influence post-infarction cardiac remodeling. Objective: To evaluate whether gender influences left ventricular (LV) remodeling and integrin-linked kinase (ILK) after myocardial infarction (MI). Methods: Female and male Wistar rats were assigned to one of three groups: sham, moderate MI (size: 20-39% of LV area), and large MI (size: ≥40% of LV area). MI was induced by coronary occlusion, and echocardiographic analysis was performed after six weeks to evaluate MI size as well as LV morphology and function. Real-time RT-PCR and Western blot were used to quantify ILK in the myocardium. Results: MI size was similar between genders. MI resulted in systolic dysfunction and enlargement of end-diastolic as well as end-systolic dimension of LV as a function of necrotic area size in both genders. Female rats with large MI showed a lower diastolic and systolic dilatation than the respective male rats; however, LV dysfunction was similar between genders. Gene and protein levels of ILK were increased in female rats with moderate and large infarctions, but only male rats with large infarctions showed an altered ILK mRNA level. A negative linear correlation was evident between LV dimensions and ILK expression in female rats with large MI. Conclusions: Post-MI ILK expression is altered in a gender-specific manner, and higher ILK levels found in females may be sufficient to improve LV geometry but not LV function.

Impact of Atrial Fibrillation Ablation on Left Ventricular Filling Pressure and Left Atrial Remodeling

Background:Left ventricular (LV) diastolic dysfunction is associated with new-onset atrial fibrillation (AF), and the estimation of elevated LV filling pressures by E/e' ratio is related to worse outcomes in patients with AF. However, it is unknown if restoring sinus rhythm reverses this process.Objective:To evaluate the impact of AF ablation on estimated LV filling pressure.Methods:A total of 141 patients underwent radiofrequency (RF) ablation to treat drug-refractory AF. Transthoracic echocardiography was performed 30 days before and 12 months after ablation. LV functional parameters, left atrial volume index (LAVind), and transmitral pulsed and mitral annulus tissue Doppler (e' and E/e') were assessed. Paroxysmal AF was present in 18 patients, persistent AF was present in 102 patients, and long-standing persistent AF in 21 patients. Follow-up included electrocardiographic examination and 24-h Holter monitoring at 3, 6, and 12 months after ablation.Results:One hundred seventeen patients (82.9%) were free of AF during the follow-up (average, 18 ± 5 months). LAVind reduced in the successful group (30.2 mL/m2 ± 10.6 mL/m2 to 22.6 mL/m2 ± 1.1 mL/m2, p < 0.001) compared to the non-successful group (37.7 mL/m2 ± 14.3 mL/m2 to 37.5 mL/m2 ± 14.5 mL/m2, p = ns). Improvement of LV filling pressure assessed by a reduction in the E/e' ratio was observed only after successful ablation (11.5 ± 4.5 vs. 7.1 ± 3.7, p < 0.001) but not in patients with recurrent AF (12.7 ± 4.4 vs. 12 ± 3.3, p = ns). The success rate was lower in the long-standing persistent AF patient group (57% vs. 87%, p = 0.001).Conclusion:Successful AF ablation is associated with LA reverse remodeling and an improvement in LV filling pressure.

Reverse Cardiac Remodeling: A Marker of Better Prognosis in Heart Failure

In heart failure syndrome, myocardial dysfunction causes an increase in neurohormonal activity, which is an adaptive and compensatory mechanism in response to the reduction in cardiac output. Neurohormonal activity is initially stimulated in an attempt to maintain compensation; however, when it remains increased, it contributes to the intensification of clinical manifestations and myocardial damage. Cardiac remodeling comprises changes in ventricular volume as well as the thickness and shape of the myocardial wall. With optimized treatment, such remodeling can be reversed, causing gradual improvement in cardiac function and consequently improved prognosis.

A Novel Algorithm to Quantify Coronary Remodeling Using Inferred Normal Dimensions

Background:Vascular remodeling, the dynamic dimensional change in face of stress, can assume different directions as well as magnitudes in atherosclerotic disease. Classical measurements rely on reference to segments at a distance, risking inappropriate comparison between dislike vessel portions.Objective:to explore a new method for quantifying vessel remodeling, based on the comparison between a given target segment and its inferred normal dimensions.Methods:Geometric parameters and plaque composition were determined in 67 patients using three-vessel intravascular ultrasound with virtual histology (IVUS-VH). Coronary vessel remodeling at cross-section (n = 27.639) and lesion (n = 618) levels was assessed using classical metrics and a novel analytic algorithm based on the fractional vessel remodeling index (FVRI), which quantifies the total change in arterial wall dimensions related to the estimated normal dimension of the vessel. A prediction model was built to estimate the normal dimension of the vessel for calculation of FVRI.Results:According to the new algorithm, “Ectatic” remodeling pattern was least common, “Complete compensatory” remodeling was present in approximately half of the instances, and “Negative” and “Incomplete compensatory” remodeling types were detected in the remaining. Compared to a traditional diagnostic scheme, FVRI-based classification seemed to better discriminate plaque composition by IVUS-VH.Conclusion:Quantitative assessment of coronary remodeling using target segment dimensions offers a promising approach to evaluate the vessel response to plaque growth/regression.

High-fat Diet Promotes Cardiac Remodeling in an Experimental Model of Obesity

AbstractBackground:Although nutritional, metabolic and cardiovascular abnormalities are commonly seen in experimental studies of obesity, it is uncertain whether these effects result from the treatment or from body adiposity.Objective:To evaluate the influence of treatment and body composition on metabolic and cardiovascular aspects in rats receiving high saturated fat diet.Methods:Sixteen Wistar rats were used, distributed into two groups, the control (C) group, treated with isocaloric diet (2.93 kcal/g) and an obese (OB) group, treated with high-fat diet (3.64 kcal/g). The study period was 20 weeks. Analyses of nutritional behavior, body composition, glycemia, cholesterolemia, lipemia, systolic arterial pressure, echocardiography, and cardiac histology were performed.Results:High-fat diet associates with manifestations of obesity, accompanied by changes in glycemia, cardiomyocyte hypertrophy, and myocardial interstitial fibrosis. After adjusting for adiposity, the metabolic effects were normalized, whereas differences in morphometric changes between groups were maintained.Conclusion:It was concluded that adiposity body composition has a stronger association with metabolic disturbances in obese rodents, whereas the high-fat dietary intervention is found to be more related to cardiac morphological changes in experimental models of diet-induced obesity.

Aerobic Training after Myocardial Infarction: Remodeling Evaluated by Cardiac Magnetic Resonance

Abstract Background: Numerous studies show the benefits of exercise training after myocardial infarction (MI). Nevertheless, the effects on function and remodeling are still controversial. Objectives: To evaluate, in patients after (MI), the effects of aerobic exercise of moderate intensity on ventricular remodeling by cardiac magnetic resonance imaging (CMR). Methods: 26 male patients, 52.9 ± 7.9 years, after a first MI, were assigned to groups: trained group (TG), 18; and control group (CG), 8. The TG performed supervised aerobic exercise on treadmill twice a week, and unsupervised sessions on 2 additional days per week, for at least 3 months. Laboratory tests, anthropometric measurements, resting heart rate (HR), exercise test, and CMR were conducted at baseline and follow-up. Results: The TG showed a 10.8% reduction in fasting blood glucose (p = 0.01), and a 7.3-bpm reduction in resting HR in both sitting and supine positions (p < 0.0001). There was an increase in oxygen uptake only in the TG (35.4 ± 8.1 to 49.1 ± 9.6 mL/kg/min, p < 0.0001). There was a statistically significant decrease in the TG left ventricular mass (LVmass) (128.7 ± 38.9 to 117.2 ± 27.2 g, p = 0.0032). There were no statistically significant changes in the values of left ventricular end-diastolic volume (LVEDV) and ejection fraction in the groups. The LVmass/EDV ratio demonstrated a statistically significant positive remodeling in the TG (p = 0.015). Conclusions: Aerobic exercise of moderate intensity improved physical capacity and other cardiovascular variables. A positive remodeling was identified in the TG, where a left ventricular diastolic dimension increase was associated with LVmass reduction.

Pentoxifylline Attenuates Cardiac Remodeling Induced by Tobacco Smoke Exposure

Abstract Background: Tobacco smoke exposure is an important risk factor for cardiac remodeling. Under this condition, inflammation, oxidative stress, energy metabolism abnormalities, apoptosis, and hypertrophy are present. Pentoxifylline has anti‑inflammatory, anti-apoptotic, anti-thrombotic and anti-proliferative properties. Objective: The present study tested the hypothesis that pentoxifylline would attenuate cardiac remodeling induced by smoking. Methods: Wistar rats were distributed in four groups: Control (C), Pentoxifylline (PX), Tobacco Smoke (TS), and PX-TS. After two months, echocardiography, invasive blood pressure measurement, biochemical, and histological studies were performed. The groups were compared by two-way ANOVA with a significance level of 5%. Results: TS increased left atrium diameter and area, which was attenuated by PX. In the isolated heart study, TS lowered the positive derivate (+dp/dt), and this was attenuated by PX. The antioxidants enzyme superoxide dismutase and glutathione peroxidase were decreased in the TS group; PX recovered these activities. TS increased lactate dehydrogenase (LDH) and decreased 3-hydroxyacyl Coenzyme A dehydrogenases (OH-DHA) and citrate synthase (CS). PX attenuated LDH, 3-OH-DHA and CS alterations in TS-PX group. TS increased IL-10, ICAM-1, and caspase-3. PX did not influence these variables. Conclusion: TS induced cardiac remodeling, associated with increased inflammation, oxidative stress, apoptosis, and changed energy metabolism. PX attenuated cardiac remodeling by reducing oxidative stress and improving cardiac bioenergetics, but did not act upon cardiac cytokines and apoptosis.

Cell-matrix interactions in Schistosomal portal fibrosis: a dynamic event

In recent years, one of the most significant progress in the understanding of liver diseases was the demonstration that liver fibrosis is a dynamic process resulting from a balance between synthesis and degradation of several matrix components, collagen in particular. Thus, fibrosis has been found to be a very early event during liver diseases, be it of toxic, viral or parasitic origin, and to be spontaneously reversible, either partially or totally. In liver fibrosis cell matrix interactions are dependent on the existence of the many factors (sometimes acting in combination) which produce the same events at the cellular and molecular levels. These events are: (i) the recruitment of fiber-producing cells, (ii) their proliferation, (iii) the secretion of matrix constituents of the extracellular matrix, and (iv) the remodeling and degradation of the newly formed matrix. All these events represent, at least in principle, a target for a therapeutic intervention aimed at influencing the experimentally induced hepatic fibrosis. In this context, hepatosplenic schistosomiasis is of particular interest, being an immune cell-mediated granulomatous disease and a model of liver fibrosis allowing extensive studies in human and animals as well as providing original in vitro models.

Morphological features of collagen degradation in advanced hepatic schistosomiasis of man

Optical and electron microscopical evidences of focal matrix degradation were frequently seen in liver sections taken from patients with periportal ("pipe-stem") fibrosis caused by schistosomiasis mansoni. Besides present of focal areas of rarefaction, fragmentation and dispersion of collagen fibers, the enlargend portal spaces also showed hyperplasia of elastic tisue and disarray of smooth muscle fibers following the destrution of portal vein branches. Ultrastructural cahnges represented by focal lytic and/or electron dense alterations of colagen fibrils were similar to those first seen in experimental material and designated as "chronic collagen degradation". Elastin and related microfibrils were also affected by focal condensation, fragmentation, distorsion and dissolution. Schistosome eggs were scanty in the tissue sections examined. Matrix degradation represented involuting changes related to the progressive diminution of parasite aggression, which occurs spontaneously with age or after cure by chemotherapy. Changes of focal matrix degradation now being described represent the basic morphological counterpart of periportal fibrosis involution documented clinically, especially by ultrasonography, in patients with hepatosplenic schistosomiasis submitted to curative chemotherapy.