Dysfunction In Left Ventricular Hypertrophy Research Articles

Left Atrial Velocity Vector Imaging Can Assess Early Diastolic Dysfunction in Left Ventricular Hypertrophy and Hypertrophic Cardiomyopathy

The function of left atrium (LA) is difficult to assess because of its ventricle-dependent, dynamic movement. The aim of this study was to assess LA function using velocity vector imaging (VVI) and compare LA function in patients with hypertrophic cardiomyopathy (HCMP) and left ventricular hypertrophy (LVH) with normal controls. Fourteen patients with HCMP (72% male, mean age of 52.6 ± 9.8), 15 hypertensive patients with LVH (88% male, mean age of 54.0 ± 15.3), and 10 age-matched controls (83% male, mean age of 50.0 ± 4.6) were prospectively studied. Echocardiographic images of the LA were analyzed with VVI, and strain rate (SR) was compared among the 3 groups. The e' velocity (7.7 ± 1.1; 5.1 ± 0.8; 4.5 ± 1.3 cm/sec, p = 0.013), E/e' (6.8 ± 1.6; 12.4 ± 3.3; 14.7 ± 4.2, p = 0.035), and late diastolic SR at mid LA (-1.65 ± 0.51; -0.97 ± 0.55; -0.82 ± 0.32, p = 0.002) were significantly different among the groups (normal; LVH; HCMP, respectively). The e' velocity, E/e', and late diastolic SR at mid LA were significantly different between normal and LVH (p = 0.001; 0.022; 0.018), whereas LA size was similar between normal and LVH (p = 0.592). The mean late diastolic peak SR of mid LA was significantly correlated with indices of diastolic function (E/e', e', and LA size). The SR is a useful tool for detailed evaluation of LA function, especially early dysfunction of LA in groups with normal LA size.

Cardiac sympathetic dysfunction in left ventricular hypertrophy caused by arterial hypertension and degenerative aortic stenosis

BackgroundTo evaluate cardiac sympathetic innervation in hypertensive patients with left ventricular (LV) hypertrophy (H) and aortic stenosis (AS) submitted to transcatheter aortic valve implantation (TAVI). Methods and ResultsTwenty-two hypertensive elders (82 ± 5 years) with severe AS and significant LVH (> 122 g·m−2 in women and > 149 g·m−2 in men) were compared with 14 patients with uncomplicated essential hypertension (HT) with similar degree of LVH and 10 controls. 123I-metaiodobenzylguanidine (MIBG) and 99mTc-tetrofosmin SPECT acquisitions were obtained to assess sympathetic innervation and LV perfusion. The innervation/perfusion mismatch score was taken as an indicator of cardiac sympathetic dysfunction. The imaging protocol was repeated 6 months after TAVI. Regional MIBG uptake was more heterogeneous in HT and AS patients than controls, and therefore, innervation/perfusion mismatch score was higher in both AS (9 ± 8) and HT (5 ± 2) than controls (1 ± 1, P < .001). On multivariate analysis, significant LVH was the major predictor of impaired LV sympathetic innervation (OR 19.45, 95% CI 1.87-201.92; P = .013). After TAVI, no differences in measures of LV sympathetic innervation were evident, although only a marginal LV mass reduction was observed (− 5.4 ± 2.4 g). ConclusionsCardiac sympathetic innervation is impaired in patients with LVH, either with AS or not, and is not impacted significantly by TAVI procedure.

Diastolic Dysfunction in Left Ventricular Hypertrophy in Hypertensive Patients with Normal Ejection Fraction

Background: Hypertension is the main cause of death and left ventricular (LV) diastolic dysfunction. LV hypertrophy (LVH) in the hypertensive patient has two types: eccentric and concentric which are classified according to the posterior wall thickness to LV end-diastolic dimensions. Aim of Study: The left ventricular diastolic function in age- and sex-matched patients with hypertension and and normal left ventricular ejection fraction was compared in the study. Patients and Methods: A total of 110 patients were enrolled in this study in Ibn Al-Bitar Cardiac Center from April 2013 to June 2014. History and examination were performed on each patient, then LV mass index (LVMI) was measured by echocardiography and patients were classified into two groups eccentric and concentric LVH. LV diastolic function was differentiated using echocardiography by measurements of left atrial volume index (LAVI), E wave, and A waves, the (E/A) ratio, transmitral deceleration time (DT), e' wave and the (E/e'). Results: LVMIs did not differ between the concentric and eccentric LVH groups. The diastolic function parameters such as LAVI, E/A ratio DT, and e' wave did not differ in both groups. Concentric LVH has E/e' significantly higher (mean ± standard deviation [SD] =12.82 ± 4.4) than those with eccentric LVH (mean ± SD = 10.37 ± 3.2). Conclusion: In patients with hypertension and LVH, concentric LVH group may be susceptible to worse diastolic dysfunction of LV than the eccentric LVH group with a similar LVMI, so we can predict the severity of diastolic dysfunction (higher E/e' ratio) by classifying LVH into concentric and eccentric.

Myocardial hypertrophy and its role in heart failure with preserved ejection fraction.

Left ventricular hypertrophy (LVH) is the most common myocardial structural abnormality associated with heart failure with preserved ejection fraction (HFpEF). LVH is driven by neurohumoral activation, increased mechanical load, and cytokines associated with arterial hypertension, chronic kidney disease, diabetes, and other comorbidities. Here we discuss the experimental and clinical evidence that links LVH to diastolic dysfunction and qualifies LVH as one diagnostic marker for HFpEF. Mechanisms leading to diastolic dysfunction in LVH are incompletely understood, but may include extracellular matrix changes, vascular dysfunction, as well as altered cardiomyocyte mechano-elastical properties. Beating cardiomyocytes from HFpEF patients have not yet been studied, but we and others have shown increased Ca(2+) turnover and impaired relaxation in cardiomyocytes from hypertrophied hearts. Structural myocardial remodeling can lead to heterogeneity in regional myocardial contractile function, which contributes to diastolic dysfunction in HFpEF. In the clinical setting of patients with compound comorbidities, diastolic dysfunction may occur independently of LVH. This may be one explanation why current approaches to reduce LVH have not been effective to improve symptoms and prognosis in HFpEF. Exercise training, on the other hand, in clinical trials improved exercise tolerance and diastolic function, but did not reduce LVH. Thus current clinical evidence does not support regression of LVH as a surrogate marker for (short-term) improvement of HFpEF.

Differential metal content and gene expression in rat left ventricular hypertrophy due to hypertension and hyperactivity

The spontaneously hypertensive rat (SHR) has been studied extensively as a model of left ventricular hypertrophy (LVH) and associated cardiac dysfunction due to hypertension (HT). The SHR also possesses a hyperactive trait (HA). Crossbreeding SHR with Wistar–Kyoto (WKY) control rats, which are nonHT and nonHA, followed by selected inbreeding produced two additional homozygous strains: WKHT and WKHA, in which the traits of HT and HA, respectively, are expressed separately. WKHT, WKHA and SHR all display LVH, but only the SHR exhibits cardiac dysfunction. We hypothesized that cardiac dysfunction in the SHR is uniquely characterized by calcium overload. We measured total cardiac Ca, Cu, Fe, K, Mg and Zn in the four strains. We found elevated Ca and depressed Cu, Mg and Zn with HT, but not unique to SHR. We surmise that HT promotes aberrant regulation of cardiac Ca2+, Cu2+, Mg2+ and Zn2+, which does not necessarily result in cardiac dysfunction. Interestingly, Cu was elevated in HA strains compared to nonHA counterparts. We then analyzed gene expression as mRNA of Cu-containing proteins, most notably mitochondrial-Cox, Dbh, Lox, Loxl1, Loxl2, Sod1 and Tyr. The gene expression profiles of Lox, Loxl1, Loxl2 and Sod1 were found especially high in the WKHA, which if reflective of protein content could account for the high Cu content in the WKHA. The mRNA of other genes, notably Mb, Fxyd1, Maoa and Maob were also examined. We found that Maoa gene expression and monoamine oxidase-A (MAO-A) protein content were low in the SHR compared to the other strains. The finding that MAO-A protein is low in the SHR and normal in the WKHT and WKHA strains is most consistent with the idea that MAO-A protects against the development of cardiac dysfunction in LVH but not against LVH in these rats.

Altered Spatiotemporal Dynamics of the Mitochondrial Membrane Potential in the Hypertrophied Heart

Chronically elevated levels of oxidative stress resulting from increased production and/or impaired scavenging of reactive oxygen species are a hallmark of mitochondrial dysfunction in left ventricular hypertrophy. Recently, oscillations of the mitochondrial membrane potential (ΔΨm) were mechanistically linked to changes in cellular excitability under conditions of acute oxidative stress produced by laser-induced photooxidation of cardiac myocytes in vitro. Here, we investigate the spatiotemporal dynamics of ΔΨm within the intact heart during ischemia-reperfusion injury. We hypothesize that altered metabolic properties in left ventricular hypertrophy modulate ΔΨm spatiotemporal properties and arrhythmia propensity.

Phosphodiesterase inhibition promotes the transition from compensated hypertrophy to cardiac dilatation in rats

The cellular signaling pathways responsible for the transition from compensated left ventricular hypertrophy (LVH) to LV dilatation (remodeling) and heart failure are unclear. As chronic administration of a beta-adrenoreceptor (beta-AR) agonist mediates the premature onset of cardiac remodeling without myocyte necrosis or myocardial dysfunction in LVH, we suggest that beta-AR activation is critical in promoting the transition from compensated LVH to cardiac dilatation. However, beta-AR mediated effects in the heart can occur via either the cyclic adenosine monophosphate (cAMP) system or via cAMP independent signaling pathways. To determine the role of cAMP in promoting adverse cardiac chamber remodeling, we evaluated whether phosphodiesterase inhibition (PDEI) promotes LV dilatation in rats with compensated LVH. The impact of chronic administration of the PDEI, pentoxifylline, on LV remodeling and function was assessed in spontaneously hypertensive rats (SHR) with compensated LVH. The PDEI mediated inotropic effects and increased cAMP concentrations in SHR. This dose of the PDEI administered for 4 months to SHR did not modify LV weight or influence intrinsic myocardial systolic function (as assessed in the absence of the PDEI) in SHR. However, the PDEI mediated the development of a right shift in LV end diastolic (LVED) pressure-internal dimension and LVED pressure-volume relations, LV wall thinning, and increments in myocardial soluble (non-cross-linked) collagen concentrations. In conclusion, chronic PDEI administration induces adverse geometric and interstitial cardiac remodeling in SHR, a finding that supports the notion that the beta-AR-cAMP system is important in mediating the progression to heart failure by promoting interstitial remodeling and LV dilatation in LVH.

Decrease of Endothelin Receptor Subtype ETB and Release of COX-Derived Products Contribute to Endothelial Dysfunction of Porcine Epicardial Coronary Arteries in Left Ventricular Hypertrophy

Alterations in the regulation of coronary circulation play a major role in the enhanced susceptibility to ischemic injury of the myocardium in left ventricular hypertrophy (LVH). The present study was designed to assess the role of endothelium-dependent contracting factors and endothelin receptors in the coronary endothelial dysfunction in LVH, occurring 2 months after aortic banding in a swine model. Hemodynamic and morphologic analyses were performed in LVH and control groups. Vascular reactivity studies were performed in rings from control and aortic banding groups to assess the contribution of endothelin (ET-1) receptor subtypes to the contraction induced by ET-1 and IRL-1620 (an ETB receptor agonist), with and without endothelium. The effects of cyclooxygenase (COX)-derived products induced by ET-1, serotonin (5-HT), and bradykinin (BK) were evaluated, with or without indomethacin (a COX antagonist). ET-1 receptor density was assessed by confocal microscopy and Western blot experiments. The wall-to-lumen ratio, determined in digital planimetry, was increased in the LVH group with no significant changes in coronary perfusion pressures. There was a significant increase in contractions to ET-1 in the LVH group, which were reduced by exposure to indomethacin and daltroban (thromboxane A2 [TXA2] receptor antagonist). Relaxations to 5-HT and BK were improved by indomethacin in the LVH group. There was no significant change in ETA receptor density (3.113 +/- 0.389 vs 3.594 +/- 0.314) but a decrease in ETB receptor density (6.435 +/- 0.265 vs 4.588 +/- 0.089; P < 0.001) in the LVH group. The coronary endothelial dysfunction of swine epicardial coronary arteries in LVH secondary to 2 months of aortic banding involves both relaxing and contracting factors. ETA receptors and COX-derived products are preferentially implicated in the increased contractions to ET-1. Strategies aimed at decreasing ET-1 effects with ET-1 antagonists selective for ETA receptors could improve the coronary endothelial dysfunction in LVH.

Specific alterations of endothelial signal transduction pathways of porcine epicardial coronary arteries in left ventricular hypertrophy.

Coronary endothelial dysfunction in left ventricular hypertrophy (LVH) can reduce myocardial perfusion and result in an impaired global LV function. The objective of this study was to characterize the specific alterations of endothelial signal transduction of coronary arteries in a swine LVH model. Aortic banding was performed 3 cm above the coronary ostia. Vascular reactivity studies were performed to assess the nitric oxide (NO) and the EDHF-mediated relaxations. There was a significant increase in LV/body weight ratio associated with an increased in LV diastolic and end-diastolic pressure and decrease in dP/dT (P < 0.05), with no significant difference in coronary pressures 60 days after pressure-overload LVH. There was a significant decrease in endothelium-dependent relaxations to serotonin (5-HT) and to bradykinin (BK) (P < 0.05 for both) from LVH animals. There was no significant decrease of relaxations in the presence of BK and Nomega-l-arginine (EDHF pathway). Plasma NO(x) levels decreased significantly from 1.8% +/- 0.2% to 1.2% +/- 0.1% (P < 0.05 versus control). Chronic pressure-overload LVH is associated with an endothelial dysfunction involving both Gi and Gq protein-mediated relaxations in coronary arteries as well as the EDHF pathway.

Impaired endothelium-dependent regulation of ventricular relaxation in pressure-overload cardiac hypertrophy.

Endothelium-derived nitric oxide (NO) selectively enhances myocardial relaxation and may benefit diastolic function. Left ventricular hypertrophy (LVH) is characterized by abnormal myocardial relaxation and endothelial dysfunction. We investigated endothelium-dependent regulation of LV relaxation in moderate pressure-overload LVH induced by aortic banding in guinea pigs. Isolated ejecting hearts of banded or sham-operated animals (shams) were studied. The specific agonists for endothelial release of NO, bradykinin (10 nmol/L), and substance P (100 nmol/L) both induced earlier onset of LV relaxation in shams (time to LV dP/dt(min) [tdP/dt(min)], -13.4+/-3.0 and -10.4+/-2.5 ms, respectively) without altering peak LV pressure or LV dP/dt(max). Neither agent altered tdP/dt(min) in banded animals. The ACE inhibitor captopril (1 micromol/L) also selectively reduced tdP/dt(min) in shams via a bradykinin/NO-dependent mechanism but had no effect in banded animals. An exogenous NO donor, sodium nitroprusside (0.1 micromol/L), selectively reduced tdP/dt(min) to a similar extent in both shams and banded animals. Endothelial-type NO synthase (eNOS) protein expression in whole LV homogenate was unaltered in banded animals. Endothelium-dependent enhancement of LV relaxation is impaired in moderate pressure-overload LVH, despite a preserved response to exogenous NO. This is not accounted for by altered eNOS expression. These abnormalities may contribute to diastolic dysfunction in LVH.

Diastolic properties in canine hypertensive left ventricular hypertrophy: Effects of angiotensin converting enzyme inhibition and angiotensin II type-1 receptor blockade

Angiotensin II has been suggested to be involved in the pathogenesis of diastolic dysfunction in left ventricular hypertrophy (LVH). The purpose of this study was to asses the effects of enalaprilat and L-158,809, an angiotensin II type-1 receptor antagonist, on LV diastolic function in 16 normal control dogs and 20 LVH dogs with perinephritic hypertension. LV hemodynamics was studied before and after intravenous injection of enalaprilat (0.25 mg/kg) or L-158,809 (0.3 mg/kg). The hemodynamic data were analyzed in relation to the changes in myocardial blood flow (measured by radioactive microspheres) and in the circulating angiotensin II and norepinephrine levels. At baseline, significant increases were observed for LV/body weight ratio as well as LV systolic and end-diastolic pressure in the LVH dogs (all P < 0.01 vs. the control group). In addition, LV relaxation time constant was prolonged and the chamber and myocardial stiffness constants were increased (P < 0.01) in the LVH dogs, suggesting an impairment of LV diastolic function. Administration of enalaprilat or L-158,809 improved LV stiffness constants in the LVH dogs (P < 0.05). The diastolic LV pressure-diameter relation shifted downwards in the LVH dogs whereas diastolic distensibility was not altered in the control dogs. Although the circulating angiotensin II levels were significantly decreased by enalaprilat in the LVH dogs, they did not correlate with the changes in the stiffness constants. Furthermore, the alterations of LV diastolic properties in the LVH group could not be attributed to myocardial perfusion, which was rather decreased by administration of enalaprilat and L-158,809. These results suggest that angiotensin II, particularly at the local level, is involved in the pathogenesis of diastolic dysfunction in pressure-overload LVH. The data also support the concept that ACE inhibitors and angiotensin II receptor blockers are potentially beneficial in the treatment of the hypertrophied heart.

Prothrombotic factors and edothelial dysfunction in left ventricular hypertrophy: Implications for thrombogenesis and atherogenesis

Prothrombotic factors and edothelial dysfunction in left ventricular hypertrophy: Implications for thrombogenesis and atherogenesis

Effects of Antihypertensive Therapy on Diastolic Dysfunction in Left Ventricular Hypertrophy

Effects of Antihypertensive Therapy on Diastolic Dysfunction in Left Ventricular Hypertrophy

Effects of Antihypertensive Therapy on Diastolic Dysfunction in Left Ventricular Hypertrophy

In systemic hypertension, a certain degree of impairment of left ventricular diastolic function is often detectable, and is the consequence of two factors: elevated afterload and left ventricular hypertrophy. The goal of improving diastolic dysfunction can thus be achieved by lowering blood pressure and by inducing a regression in left ventricular hypertrophy. A reduction in blood pressure by intravenous administration of verapamil has proved capable of enhancing left ventricular filling properties in patients with hypertension. This finding has not been corroborated, however, in midterm protocols using an array of drugs (beta-blockers, dihydropyridines, diltiazem, and diuretics). Reduction in left ventricular mass can be achieved by several categories of drugs, and it has been shown that a decrease in mass is accompanied by an improvement in the early diastolic filling pattern. The kind of drug used to accomplish mass reduction seems to be irrelevant as far as the improvement in diastolic function is concerned. The pattern of left ventricular hypertrophy, however, might play a role in influencing the outcome on diastolic mechanics of left ventricular mass decrease.

Abnormal diastolic left ventricular posterior wall motion in left ventricular hypertrophy

The left ventricular pressure-volume relationship is abnormal in left ventricular hypertrophy (LVH). As a result, the left atrium empties more slowly than normal during the rapid filling phase of diastole, producing a characteristic abnormality of diastolic aortic root motion. In order to determine whether this altered LV filling is accompanied by a derangement of diastolic LV wall motion which might be useful in identifying the presence of altered chamber compliance, the M-mode echocardiograms of 60 patients with LVH secondary to aortic stenosis, hypertrophic subaortic stenosis, or hypertension, and those of 36 normal individuals were evaluated. Patients with LVH demonstrated abnormal LV posterior wall motion manifested by prolonged phases of rapid ventricular filling and atrial contraction ( p < 0.01 and p < 0.05, respectively). The early diastolic wall motion abnormality can be readily detected by visual inspection of the echocardiogram. These findings support the concept of diastolic dysfunction in LVH and represent another echocardiographic feature of that condition.