Diastolic dysfunction, hypertrophy and hypertension ventricular-arterial uncoupling treatment.

The aim of the study was to evaluate hypertension treatment effects on mechanical efficiency of the cardiovascular system and cardiac reverse remodeling in hypertensive patients. This is an observational prospective study, consecutive hypertension patients. Left ventricle mass index measured by Devereux 2D method and diastolic function following the Guidelines from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. Left ventricular end systolic elastance (Ees) was measured by Guarracino calculator, the effective arterial elastance (Ea) and ventricular-arterial coupling (VAC) measured by Sunagawa et al. single beat method adapted by Chen et al. in human ventricles. The sample was analyzed in quartiles (Q) according to VAC. Follow-up 2 years. In total, 288 patients, mean age 56.3 ± 12.5 years and 168 patients (58.3%) males. VAC increased from 0.303 ± 0.07 to 0.54 ± 0.25 (p < 0.005) in Q1 mainly due to a reduction in Ees from 5.25 ± 2.3 to 3.68 ± 0.25 mmHg/ml (p < 0.01), while Ea increased from 1.5 ± 0.53 to 1.64 ± 0.56 mmHg/ml (p = NS). The frequency of LVH was reduced from 31.9 to 10.8% in Q1 (p < 0.025). The frequency of normal diastolic function increased from 75 to 94.6% (p < 0.01) in Q1, from 78.7 to 100% in Q2 (p < 0.005), from 87.1 to 100% (p < 0.025) in Q3 and from 88.7 to 100% (0,025) in Q4. Patients with the worst ventricular-arterial uncoupling were the most benefited from hypertension treatment. Regression of left ventricular hypertrophy was observed only in the group of patients with the worst ventricular-arterial uncoupling, while improvement in diastolic function was demonstrated in all quartiles of patients.

Reverse Remodeling in Human Heart Failure after Cardiac Resynchronization Therapy Is Associated With Reduced RHO-Kinase Activation.

Background: Reverse remodeling is a clinically relevant endpoint in heart failure with reduced ejection fraction (HFrEF). Rho-kinase (ROCK) signaling cascade activation correlates with cardiac remodeling and left ventricular (LV) systolic dysfunction in HFrEF patients. Cardiac resynchronization therapy (CRT) is effective in HFrEF, especially when there is a left bundle block, as this treatment may stimulate reverse remodeling, thereby improving quality of life and prolonging survival for patients with this severe condition. Here, we evaluate the hypothesis that ROCK activation is reduced after effective CRT in HFrEF. Methods: ROCK activation in circulating leukocytes was evaluated in 28 HFrHF patients, using Western blot (myosin light chain phosphatase subunit 1 phosphorylation, MYPT1p/t), before and three months after initiation of CRT. LV systolic function and remodeling were assessed by echocardiography. Results: Three months after CRT, LV ejection fraction increased an average of 14.5% (p < 0.001) in 13 patients (responders), while no change was observed in 15 patients (non-responders). End-systolic diameter decreased 16% (p < 0.001) in responders, with no change in non-responders. ROCK activation in PBMCs decreased 66% in responders (p < 0.05) but increased 10% in non-responders (NS). LV end-diastolic diameter was also 5.2 mm larger in non-responders vs. responders (p = 0.058). LV ejection fraction, systolic diameter, and ROCK activation levels were similar in both groups at baseline. Conclusion: In HFrEF patients, 3 months of effective CRT induced reverse myocardial remodeling, and ROCK activation was significantly decreased in circulating leukocytes. Thus, decreased ROCK activation in circulating leukocytes may reflect reverse cardiac remodeling in patients with heart failure.

Hypertensive heart disease: Benefit of carvedilol in hemodynamic, left ventricular remodeling, and survival.

OBJECTIVES: The aim of this study was to determine if carvedilol improved structural and functional changes in the left ventricle and reduced mortality in patients with hypertensive heart disease. METHODS: Blood pressure, heart rate, echocardiographic parameters, and laboratory variables, were assessed pre and post treatment with carvedilol in 98 eligible patients. RESULTS: Carvedilol at a median dose of 50 mg/day during the treatment period in hypertensive heart disease lowered blood pressure 10/10 mmHg, heart rate 10 beats/min, improved left ventricular ejection fraction from baseline to follow-up (median: 6 years) (36%-47%)) and reduced left ventricular end-diastolic and end-systolic dimensions (62 vs 56 mm; 53 vs 42 mm, respectively, all p-values <0.01). Left ventricular ejection fraction increased in 69% of patients. Patients who did not have improved left ventricular ejection fraction had nearly six-fold higher mortality than those that improved (relative risk; 5.7, 95% confidence interval: 1.3-25, p = 0.022). CONCLUSION: Carvedilol reduced cardiac dimensions and improved left ventricular ejection fraction and cardiac remodeling in patients with hypertensive heart disease. These treatment-related changes had a favorable effect on survival.

Rho kinase activation in circulating leukocytes is related to hypertensive myocardial remodeling.

Rho-kinase has relevant functions in blood pressure modulation and cardiovascular remodeling. Rho-kinase activity is determined in circulating leukocytes measuring phosphorylation of its target myosin phosphatase target subunit 1 (MYPT1), but its relationship with Rho-kinase activity in the myocardium and in vasculature in hypertension has not been evaluated.The aim was to determine the degree of association between Rho-kinase cascade activation in circulating leukocytes with cardiac and aortic Rho-kinase pathway activation in a model of hypertension and to analyze it with a cause-effect perspective.Hypertensive deoxycorticosterone (DOCA)-salt rats received the Rho-kinase antagonist fasudil (DOCA-Fas, 100 mg/kg/day, 3 weeks). Results were compared with an untreated DOCA-salt and a sham group.Rho-kinase inhibition reduced significantly blood pressure, cardiac hypertrophy, myocardial collagen and macrophage infiltration, but not aortic wall hypertrophy. Fasudil decreased significantly Rho-kinase activity in peripheral blood mononucleated cells (PBMC), myocardium and aortic wall to similar levels as in the sham group. A significant correlation was found between PBMC Rho-kinase activity and cardiac remodeling, specifically with hypertrophy (r = 0.51, P≤0.01), myocardial collagen (r = 0.40, P≤0.05) and ED1 immunostaining (r = 0.48, P≤0.01). In the untreated hypertensive group, increased levels (P<0.05) of the proinflammatory molecules p65 NF-κB, vascular cell adhesion molecule 1 and interleukin-6 antibody in the myocardium, aortic wall and PBMC were observed and were reduced with fasudil (P<0.05).In conclusion, in this hypertension model, Rho-kinase and its pathway activation determined in circulating leukocytes reflect the activation of this pathway in the myocardium and in the aortic wall and are significantly related to myocardial remodeling (hypertrophy, fibrosis and inflammation).

"Hiper-resposta" avaliada pelo eco 3D após terapia de ressincronização cardíaca / "Hyper-response" evaluated by 3D echocardiography after cardiac resynchronization therapy / "Hiperrespuesta" evaluada por el eco 3D después de la terapia de resincronización cardíaca

A terapia de ressincronização cardíaca consiste em tratamento promissor para pacientes com insuficiência cardíaca grave, porém cerca de 30 por cento dos pacientes não apresentam melhora clínica com este tratamento. Por outro lado, aproximadamente 10 por cento dos pacientes submetidos a essa terapia podem apresentar hiper resposta, e a ecocardiografia tridimensional pode oferecer uma opção interessante para a seleção e avaliação de tratamento desses pacientes.

Cardiac resynchronization therapy consists of a promising treatment for patients with severe heart failure, but about 30 percent of patients do not exhibit clinical improvement with this procedure. However, approximately 10 percent of patients undergoing this therapy may have hyperresponsiveness, and three-dimensional echocardiography can provide an interesting option for the selection and evaluation of such patients.

La terapia de resincronización cardíaca consiste en un tratamiento promisorio para pacientes con insuficiencia cardíaca grave, sin embargo cerca de un 30 por ciento de los pacientes, no presentan una mejoría clínica con ese tratamiento. Por otro lado, aproximadamente un 10 por ciento de los pacientes sometidos a esa terapia pueden presentar hiperrespuesta, y la ecocardiografía tridimensional puede ser una opción interesante para la selección y la evaluación del tratamiento de esos pacientes.