Left ventricular hypertrophy. Relation of structure to diastolic function in hypertension

Digitised M mode echocardiography was used to determine the relation between the degree of left ventricular hypertrophy and abnormalities of isovolumic relaxation and diastolic function. Fifty six patients with varying severity of non-malignant systemic hypertension without evidence of ischaemic heart disease, left ventricular dilation, or clinical heart failure were studied. In addition, 10 athletes with hypertrophy and 20 normal subjects were studied. Athletes and patients with moderate (systolic blood pressure 175 to 200 mm Hg) and severe hypertension (greater than 200 mm Hg) had a significant increase in left ventricular mass. Cavity dimensions were normal in hypertensive patients and increased in athletes. Systolic function was normal in all groups. Regardless of the degree of hypertrophy patients with hypertension had a prolonged isovolumic relaxation period and delayed mitral valve opening. Patients with hypertrophy also had a reduced rate and prolonged duration of rapid early diastolic dimension increase and posterior wall thinning. Athletes, however, who had an equivalent degree of hypertrophy to patients with moderate or severe hypertension had entirely normal function. Measurements of diastolic function were significantly correlated with wall thickness and left ventricular mass. These indices of hypertrophy, particularly posterior wall thickness and the sum of posterior wall and septal thickness, were positively correlated with the duration of isovolumic relaxation and delay in mitral opening and negatively with the peak rate of early diastolic dimension increase and wall thinning. Thus in hypertensive patients with non-dilated left ventricular hypertrophy there appears to be a relation between the degree of wall thickening and abnormalities of diastolic function.     

Left ventricular hypertrophy. Relation of structure to diastolic function in hypertension.

Digitised M mode echocardiography was used to determine the relation between the degree of left ventricular hypertrophy and abnormalities of isovolumic relaxation and diastolic function. Fifty six patients with varying severity of non-malignant systemic hypertension without evidence of ischaemic heart disease, left ventricular dilation, or clinical heart failure were studied. In addition, 10 athletes with hypertrophy and 20 normal subjects were studied. Athletes and patients with moderate (systolic blood pressure 175 to 200 mm Hg) and severe hypertension (greater than 200 mm Hg) had a significant increase in left ventricular mass. Cavity dimensions were normal in hypertensive patients and increased in athletes. Systolic function was normal in all groups. Regardless of the degree of hypertrophy patients with hypertension had a prolonged isovolumic relaxation period and delayed mitral valve opening. Patients with hypertrophy also had a reduced rate and prolonged duration of rapid early diastolic dimension increase and posterior wall thinning. Athletes, however, who had an equivalent degree of hypertrophy to patients with moderate or severe hypertension had entirely normal function. Measurements of diastolic function were significantly correlated with wall thickness and left ventricular mass. These indices of hypertrophy, particularly posterior wall thickness and the sum of posterior wall and septal thickness, were positively correlated with the duration of isovolumic relaxation and delay in mitral opening and negatively with the peak rate of early diastolic dimension increase and wall thinning. Thus in hypertensive patients with non-dilated left ventricular hypertrophy there appears to be a relation between the degree of wall thickening and abnormalities of diastolic function.     

Renal sympathetic denervation reduces left ventricular hypertrophy and improves cardiac function in patients with resistant hypertension

This study investigated the effect of catheter-based renal sympathetic denervation (RD) on left ventricular hypertrophy (LVH) and systolic and diastolic function in patients with resistant hypertension. LVH and diastolic dysfunction are associated with elevated sympathetic activity and increased morbidity and mortality. The effect of RD on LVH and LV function is unclear.Methods and Results Forty-six patients underwent bilateral RD , and 18 patients served as controls. Transthoracic echocardiography was performed at baseline, and after 1 month and 6 months. Besides reduction of systolic and diastolic blood pressure (-22.5 / -7.2 mmHg at 1 month and -27.8 / -8.8 mmHg at 6 months, P < 0.001 at each time point), RD significantly reduced mean interventricular septum thickness from 14.1 ± 1.9 mm to 13.4 ± 2.1 mm and 12.5 ± 1.4 mm (P = 0.007), and LV mass index from 53.9 ± 15.6 g / m(2.7) (112.4 ± 33.9 g / m(2)) to 47.0 ± 14.2 g / m(2.7) (103.6 ± 30.5 g / m(2)) and 44.7 ± 14.9 g / m (2.7) (94.9 ± 29.8 g / m(2)) (P < 0.001) at 1 month and 6 months, respectively. The mitral valve lateral E / E’ decreased after RD from 9.9 ± 4.0 to 7.9 ± 2.2 at 1 month and 7.4 ± 2.7 at 6 months (P < 0.001), indicating reduction of LV filling pressures. Isovolumic relaxation time shortened (baseline 109.1 ± 21.7 ms vs. 85.6 ± 24.4 ms at 6 months, P = 0.006), whereas ejection fraction significantly increased after RD (baseline: 63.1 ± 8.1% vs. 70.1 ± 11.5% at 6 months, P < 0.001). No significant changes were obtained in control patients. Conslusions Besides the known effect on blood pressure , our study showed for the first time that RD significantly reduces LV mass and improves diastolic function, which might have important prognostic implications in patients with resistant hypertension at high cardiovascular risk.     

单纯收缩期高血压患者血管内皮功能与左心室肥厚的关系

目的探讨单纯收缩期高血压患者血流介导的血管舒张功能(FMD)与左心室肥厚(LVH)的关系。方法选择单纯收缩期高血压患者200例,根据左心室质量指数分为:LVH组73例和非LVH组127例,同期选择年龄匹配的健康体检者50例作为对照组,采用超声技术测定FMD,ELISA法检测外周血清晚期糖基化终末产物(AGEs)和内皮素1,Griess法测定外周血NO含量。结果与非LVH组和对照组比较,LVH组FMD明显降低,AGEs和内皮素1均明显升高(P0.01)。左心室质量指数与AGEs和内皮素1呈显著正相关(r=0.639,P=0.015;r=0.428,P=0.036),与FMD和NO呈显著负相关(r=-0.718,P=0.003;r=-0.337,P=0.041);FMD和AGEs为LVH的独立危险因素(P=0.027,P=0.035);随着FMD降低、AGEs增加,LVH发病的危险性明显增加。结论血管内皮功能减退和大动脉硬化是单纯收缩期高血压患者LVH的独立危险因素。     

Altered sympathetic system and adrenoceptors during the development of cardiac hypertrophy

Increasing experimental evidence suggests that the development of cardiac hypertrophy may involve the sympathetic system and associated receptor mechanisms. However, very little work has been done so far to understand changes in the sympathetic system and cardiac adrenoceptors soon after an increased work load is imposed on the heart. Accordingly rat hearts subjected to aortic banding-induced pressure overload were assessed 3, 7, and 14 days postoperatively. Sham-operated rats without aortic banding were used as a control group. Rats with aortic constriction had increases in heart rate, left ventricular systolic pressure, and total mechanical energy during the entire study period. The cardiac RNA level was increased without a significant increase in left ventricular mass on days 3 and 7 in aortic-banded animals; these results were associated with a decrease in the cardiac norepinephrine (NE) store and an increase in the plasma level of NE and dopamine beta-hydroxylase (DBH) activity. By day 14 a significant increase in left ventricular mass and the NE store were found; both plasma NE and DBH remained elevated. Catecholamines in other tissues such as the spleen and kidney were depleted in the banded group, whereas the dopamine level, particularly in the brain, was significantly higher during the entire study. Furthermore, the density of alpha-adrenoceptors was higher on day 3 of aortic banding, and a reciprocal correlation was evident between cardiac alpha- and beta-adrenoceptors on day 14; the density of beta-adrenoceptors was increased, whereas that of alpha-adrenoceptors was decreased in the banded group.(ABSTRACT TRUNCATED AT 250 WORDS)     

Echocardiographic and ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension.

High-resolution ultrasonography is a noninvasive technique that allows to investigate the cardiovascular system, in particular the wall thickness and the lumen diameter of the arteries with accuracy and reproducibility. We measured the intima-media thickness of the common carotid artery (CCA) and of its bifurcation (BIF) in 40 patients with essential hypertension, 20 of them with left ventricular hypertrophy (LVH; age 42 +/- 10 years) and 20 without LVH (age 44 +/- 12 years); no other major cardiovascular risk factor was present in all the patients. Both carotid axes have been scanned from different views (anterior, lateral, posterior) on a transversal and longitudinal section using a high-resolution steerable linear array of 5.0 MHz. Carotid diameter and thickness were measured in the longitudinal section. CCA parameters were assessed 20 mm caudally to the flow divider. In patients with LVH, blood pressure (172 +/- 21/108 +/- 9 mm Hg) and left ventricular mass index (156 +/- 38 g/m2) were significantly (p < 0.01) higher than in patients without LVH (blood pressure: 158 +/- 11/99 +/- 12 mm Hg; left ventricular mass index: 98 +/- 10 g/m2), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness of both the CCA and BIF was significantly higher in the hypertensives with LVH (CCA: 0.85 +/- 0.02 vs. 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 vs. 0.70 +/- 0.03 mm, p < 0.01). There was a statistically significant correlation between the carotid wall thickness and the left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Relationship between insulin resistance and cardiac sympathetic nervous function in essential hypertension.

BACKGROUND: It has been suggested that hyperinsulinemia and insulin resistance participate in the pathogenesis of hypertension, in part by activating sympathetic activity. OBJECTIVE: We aimed to examine the relationship between insulin resistance and cardiac sympathetic nervous function in patients with essential hypertension using 123I-metaiodobenzylguanidine (MIBG) cardiac scintigraphy. METHODS AND RESULTS: Twenty-eight patients (18 men) with essential hypertension and 11 (seven men) control individuals with a mean age of 55.8+/-3.3 years were recruited. Patients with diabetes mellitus, congestive heart failure or coronary artery disease were excluded from this study. To evaluate insulin resistance, we used steady-state plasma glucose (SSPG; mg/dl) levels measured by the SSPG method. To evaluate cardiac sympathetic nervous function, we calculated the heart-to-mediastinum ratio from the delayed MIBG image (H:M-D) and the mean washout rate (WOR, %). There were significant differences (P<0.01) in SSPG, H:M-D and WOR between the essential hypertension and control individual groups (125 versus 103 mg/dl, 2.2 versus 2.4, and 32 versus 23%, respectively). Stepwise regression analysis showed that SSPG and plasma norepinephrine level are independent predictors for the cardiac sympathetic nervous function obtained from MIBG scintigraphy. CONCLUSIONS: These findings indicate that insulin resistance is significantly related to activation of the cardiac sympathetic nervous function associated with left ventricular hypertrophy in patients with essential hypertension.     

The role of the renin-angiotensin and cardiac sympathetic nervous systems in the development of hypertension and left ventricular hypertrophy in spontaneously hypertensive rats.

To elucidate the relationship between the development of left ventricular hypertrophy (LVH) in hypertension and the development of both the cardiac sympathetic nervous and renin-angiotensin systems, as measured by norepinephrine and angiotensin II levels, respectively. In this longitudinal study, we compared blood pressure (BP), left ventricular weight, and norepinephrine (NE) and angiotensin II (Ang II) concentrations, in Spontaneously Hypertensive Rats (SHR) and age-matched Wistar-Kyoto (WKY) rats at 5, 10, 15, 20, and 28 wk of age. Blood pressure, plasma and ventricular Ang II and tissue NE were measured by the tail-cuff method, radioimmunoassay, and high-performance liquid chromatography (HPLC), respectively. At 5 wk, systolic blood pressure was the same in both strains. But the left ventricular plus septum weight to body weight (LVSW/BW) ratio was higher in SHR than in WKY rats (p < 0.01), which finding may have been related to the increased cardiac tissue NE concentration, and this increase tended to parallel the rise in blood pressure. Both left ventricle and forelimb muscle NE concentrations were significantly higher in SHR than in WKY rats at 5, 10, and 15 wk of age (p < 0.01, respectively), and were similar at 20 and 28 wk of age. The heart and plasma Ang II levels decreased with age, which results were in keeping with the known developmental tendencies of the biological aging progress. There was no significant difference in plasma Ang II levels between the two strains from 5 to 20 wk, whereas these levels were remarkably higher in WKY than in SHR rats at 28 wk (p< 0.01). Otherwise, the left ventricular tissue Ang II concentrations were significantly higher in SHR than in WKY rats at the late stage (from 15 to 28 wk), which may have contributed to the late-stage cardiac hypertrophy. These results suggested that the sympathetic nervous system (SNS) and the renin-angiotensin-system (RAS) in SHR may contribute to the pathogenesis of hypertension and LVH at the early and late stages, respectively.     

Cardiac sympathetic rejuvenation: a link between nerve function and cardiac hypertrophy

Neuronal function and innervation density is regulated by target organ-derived neurotrophic factors. Although cardiac hypertrophy drastically alternates the expression of various growth factors such as endothelin-1, angiotensin II, and leukemia inhibitory factor, little is known about nerve growth factor expression and its effect on the cardiac sympathetic nerves. This study investigated the impact of pressure overload-induced cardiac hypertrophy on the innervation density and cellular function of cardiac sympathetic nerves, including kinetics of norepinephrine synthesis and reuptake, and neuronal gene expression. Right ventricular hypertrophy was induced by monocrotaline treatment in Wistar rats. Newly developed cardiac sympathetic nerves expressing beta(3)-tubulin (axonal marker), GAP43 (growth-associated cone marker), and tyrosine hydroxylase were markedly increased only in the right ventricle, in parallel with nerve growth factor upregulation. However, norepinephrine and dopamine content was paradoxically attenuated, and the protein and kinase activity of tyrosine hydroxylase were markedly downregulated in the right ventricle. The reuptake of [(125)I]-metaiodobenzylguanidine and [(3)H]-norepinephrine were also significantly diminished in the right ventricle, indicating functional downregulation in cardiac sympathetic nerves. Interestingly, we found cardiac sympathetic nerves in hypertrophic right ventricles strongly expressed highly polysialylated neural cell adhesion molecule (PSA-NCAM) (an immature neuron marker) as well as neonatal heart. Taken together, pressure overload induced anatomical sympathetic hyperinnervation but simultaneously caused deterioration of neuronal cellular function. This phenomenon was explained by the rejuvenation of cardiac sympathetic nerves as well as the hypertrophic cardiomyocytes, which also showed the fetal form gene expression.     

Ultrasonographic evaluation of cardiac and vascular hypertrophy in patients with essential hypertension]

High resolution ultrasonography allows the accurate and reproducible measurement of thickness and lumen diameter of carotid arteries. We investigated Common carotid (CCA) and bifurcation intima-media thickness in 40 hypertensive patients, 20 without left ventricular hypertrophy (LVH) (age 42 +/- 10 years) and 20 with LVH (age 44 +/- 12 years), all free from other important cardiovascular risk factors. Both carotid axes were scanned from different views (anterior, lateral, posterior) on traversal and longitudinal section, using a high resolution steerable (HRS) 5.0 MHz linear array. Carotid diameter and thickness from longitudinal section were measured. CCA parameters were taken 20 mm caudally to flow divider. Using the B-mode as a guide we assessed LVH presence with M-mode technique when left ventricular mass index (LVMI) > or = 135 g/m2 for men and > or = 110 g/m2 for women. In hypertensive patients with LVH, left ventricular mass was significantly higher than in those without LVH (156 +/- 38 vs 98 +/- 10 g/m2, p < 0.01). Even blood pressure was significantly higher in hypertrophic group (172 +/- 21/108 +/- 9 vs 158 +/- 11/99 +/- 12 mmHg, p < 0.01), while there was no difference in serum glycemia, triglycerides, total and fractioned cholesterol levels. The intima-media thickness scanned in both CCA and bifurcation resulted significantly higher in hypertensives with LVH (CCA: 0.85 +/- 0.02 mm vs 0.65 +/- 0.02 mm; BIF: 0.93 +/- 0.04 mm vs 0.70 +/- 0.03 mm, p < 0.01). We also noticed a statistically significant correlation between carotid wall thickness and left ventricular mass index.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of celiprolol on cardiac hypertrophy in hypertension.

The present study was undertaken to clarify whether celiprolol and atenolol, beta1-selective beta blockers with and without intrinsic sympathomimetic activity (ISA), respectively, might improve ischemic damage in the isolated perfused hearts of spontaneously hypertensive rats (SHR), and whether long-term treatment with celiprolol may reduce left ventricular hypertrophy (LVH) in patients with essential hypertension. Atenolol (50 mg/kg/day) or celiprolol (300 mg/kg/day) for 7 weeks significantly reduced the blood pressure in SHR to the same degree, and both drugs decreased the heart rate, but the magnitude of the fall in heart rate was significantly higher with atenolol treatment than with celiprolol treatment. Both treatments significantly reduced the ratio of LV weight to body weight in SHR and significantly improved the coronary reserve in SHR to the same extent. Both treatments significantly improved the extent of recovery of the pressure-rate product and the extent of percent recovery of the coronary flow after reperfusion following 30 min of ischemia in SHR. Celiprolol treatment in patients with essential hypertension for 12 months significantly decreased interventricular septal thickness (IVST)+LV posterior wall thickness (PWT) and LV mass index (LVMI), but there was no significant correlation between IVST+PWT or LVMI and blood pressure before and after treatment. IVST+PWT and LVMI were significantly decreased after 3 months of treatment and these LVH indices were significantly smaller after 6 and 12 months of treatment than after 3 months of treatment. In conclusion, both celiprolol and atenolol treatment reduced LVH and improved the ischemic damage in SHR. In essential hypertensive patients with LVH, celiprolol treatment effectively reduced blood pressure and achieved LVH regression.     

MEF2 in cardiac hypertrophy in response to hypertension

Hypertension is a globally prevalent pathological condition and an underlying risk factor for the development of cardiac hypertrophy leading to heart failure. Myocyte enhancer factor 2 (Mef2) has been identified as one of the primary effectors of morphological changes in the hypertensive heart, as part of a complex network of molecular signaling controlling cardiac gene expression. Experimental chronic pressure-overload models that mimic hypertension in the mammalian heart lead to the activation of various pathological mechanisms that result in structural changes leading to debilitating cardiac hypertrophy and ultimately heart failure. The purpose here is to survey the literature implicating Mef2 in hypertension induced cardiac hypertrophy, towards illuminating points of interest for understanding and potentially treating heart failure.     

Myocardial gene expression associated with genetic cardiac hypertrophy in the absence of hypertension

The hypertrophic heart rat (HHR) was derived from the spontaneously hypertensive rat of the Okamoto strain and develops cardiac hypertrophy in the absence of hypertension. The genetic basis of this hypertrophy is unknown. Therefore, we compared gene expression profiles in the left ventricular myocardium of young (8-10 weeks of age) and old (38-50 weeks) HHR with rats from an age-matched control strain, the normal heart rat (NHR). cDNA microarrays (National Institute of Aging [NIA], 15,247 clones) were used to evaluate gene expression in cardiac-derived Cy3 and Cy5 labeled cDNA. M values (log2[Cy5/Cy3]) were obtained and significant differential expression was identified using an empirical Bayesian approach with specific results verified using real-time PCR. Compared with NHR, HHR cardiac weight index (heart weight/ body weight) was significantly elevated at both ages (young: 5.5 +/- 0.5 vs. 3.9 +/- 0.2; old: 4.2 +/- 0.3 vs. 3.4 +/- 0.2 mg/g; p < 0.05) with no difference in body weight or in tail-cuff blood pressure detected between the strains at either age. Differential expression was observed in 65 and 390 clones in young and old HHR, respectively, with more genes exhibiting down-regulation than up-regulation in both instances (young: down 44 vs. up 21; old: down 292 vs. up 98). Our data suggest a role for the Ras/mitogen-activated protein kinase (MAPK) signaling pathway and the tumor necrosis factor (TNF) receptor-mediated activation of nuclear factor-kappaB (NF-kappaB) in the etiology of cardiac enlargement in the HHR. These findings support the candidature of previously identified cardiotrophic agents in contributing to the cardiac enlargement in the normotensive HHR, and also identify novel genetic factors which may be involved in the genesis of primary cardiac hypertrophy.