Marker Of Left Ventricular Hypertrophy Research Articles

Electrocardiographic Strain Pattern in Children With Left Ventricular Hypertrophy: A Marker of Ventricular Dysfunction

The objective of this study was to assess the relation between strain pattern on electrocardiogram (ECG-strain) and echocardiographic indices of left ventricular (LV) structure and function in children with LV hypertrophy (LVH). ECG-strain is a marker of LVH and is associated with adverse cardiovascular prognosis in adults. The significance of ECG-strain and its relation to LV structure and function has not been studied in children. We retrospectively analyzed electrocardiograms (ECGs) and echocardiograms of 101 children enrolled in this study. Subjects were divided into three groups: group I (n = 21) comprised children with LVH confirmed by echocardiography (LVH(echo)) with ECG-strain pattern; group II (n = 54) comprised children with LVH(echo) without ECG-strain pattern; and group III (n = 26) comprised children without LVH (control group). ECG-strain was defined as a down-sloping convex ST-segment depression (> or = 0.1 mV) with an inverted asymmetrical T-wave opposite to the QRS axis in leads V5 and/or V6. LV structure and function was measured using conventional and tissue Doppler echocardiography. ECG-strain was associated with greater interventricular septal thickness, posterior wall thickness, and LV mass index (LVMI) compared with those without ECG-strain (P < 0.0001 for each variable). Concentric LVH was more common in those with ECG-strain (16 of 21 vs. 9 of 54 patients; P = < 0.0001). ECG-strain was associated with systolic, diastolic, and combined systolic-diastolic dysfunction in children with LVH(echo). Among children with LVH, ECG-strain is associated with higher LVMI, concentric pattern of LVH, and LV systolic and diastolic dysfunction. Whether this has similar adverse prognostic implications as it does in adults remains to be determined.

Novel Markers of Left Ventricular Hypertrophy in Uremia

Aims: Left ventricular hypertrophy (LVH) is the most frequent cardiac complication in chronic renal disease. Previous studies implicate elevated serum phosphorus as a risk factor for LVH. Methods: We treated 5/6 nephrectomized rats with enalapril or enalapril + sevelamer carbonate for 4 months to determine if sevelamer carbonate had an additional beneficial effect on the development of LVH and uremia-induced left ventricle (LV) remodeling. Results: Uremia increased LV weight and cardiomyocyte size. Enalapril and enalapril + sevelamer blunted the increase in left ventricular weight. Only enalapril + sevelamer diminished the increase in cardiomyocyte size. Uremia increased cyclin D2 and PCNA and decreased p27 protein expression in the heart. Enalapril + sevelamer diminished the decrease in p27 expression caused by uremia. Uremia increased Ki67-positive and phosphohistone H₃-positive interstitial cells. This was not seen in cardiomyocytes. Multivariable regression analysis showed that increased phosphorus was an independent risk factor for both increased LV weight and cardiomyocyte size. Conclusions: These data suggest left ventricular remodeling consists of cardiomyocyte hypertrophy and interstitial cell proliferation, but not cardiomyocyte proliferation. p27 and cyclin D2 may play important roles in the development of LVH. In addition, phosphorus can be an independent risk factor for the development of LVH.

Plasma adiponectin levels are associated with left ventricular hypertrophy in a random sample of middle-aged subjects

Background. A low adiponectin level is associated with high blood pressure which, in turn, often results in left ventricular hypertrophy. We evaluated the association between plasma adiponectin concentrations and echocardiographic measurements, including left ventricular mass index (LVMI), in 933 middle-aged subjects consisting of 453 hypertensives and 480 controls.Methods. Plasma adiponectin concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) method. One experienced cardiologist performed echocardiographic examinations, and LVMI was calculated according to Devereux’s method.Results. Low plasma adiponectin levels were independently associated with increased intraventricular septum thickness, posterior ventricular wall thickness, and left ventricular mass index (P<0.001) in the whole cohort. In the subgroup analysis, the association between these echocardiographic parameters and adiponectin concentrations was observed only in the hypertensive cohort although fractional shortening revealed an association with adiponectin levels also in the control cohort (P=0.021). Findings remained significant after adjustment for the major risk factors for LVMI, such as age, sex, smoking, and systolic blood pressure.Conclusions. This study in a large population sample detected an association between low plasma adiponectin concentration and LVMI, a marker of left ventricular hypertrophy. This association may be one of the factors that could explain the reported increased cardiovascular risk in subjects with low adiponectin levels.

Enhanced hypertrophy in ob/ob mice due to an impairment in expression of atrial natriuretic peptide

Rationale We investigated the molecular mechanism(s) that play a role in leptin signaling during the development of left ventricular hypertrophy (LVH) due to pressure overload. To this end, ob/ob leptin deficient and C57BL/6J control mice were subjected transverse aortic constriction (TAC). Methods Control sham C57BL/6J and ob/ob mice, along with C57BL/6J and ob/ob leptin deficient mice were subjected transverse aortic constriction (TAC) for 15 days and then evaluated for morphological, physiological, and molecular changes associated with pressure overload hypertrophy. Results Evaluation by echocardiography revealed a significant increase in left ventricular mass (LVmass) and wall thickness in ob/ob mice subjected to transverse aortic constriction (TAC) as compared to C57BL/6J. Analysis of the expression of molecular markers of LVH, such as atrial natriuretic peptide (ANP), revealed a blunted increase in the level of ANP in ob/ob mice as compared to C57BL/6J mice. We observed that leptin plays a role in modulating the transcriptional activity of the promoter of the ANP gene. Leptin acts by regulating NFATc4, a member of the nuclear factor activated T cell (NFAT) family of transcription factors in cardiomyocytes. Our in vivo studies revealed that ob/ob mice subjected to TAC failed to activate the NFATc4 in the heart, however, intraperitoneal injection of leptin in ob/ob mice restored the NFATc4 DNA-binding activity and induced expression of the ANP gene. Conclusion This study establishes the role of leptin as an anti-hypertrophic agent during pressure overload hypertrophy, and suggests that a key molecular event is the leptin mediated activation of NFATc4 that regulates the transcriptional activation of the ANP gene promoter.

Cornell Product Left Ventricular Hypertrophy in Electrocardiogram and the Risk of Stroke in a General Population

Left ventricular hypertrophy (LVH), assessed by ECG, is associated with an increased risk for cardiovascular events among hypertensive subjects. We evaluated the risks of LVH in a Japanese general population including normotensive and prehypertensive subjects. We measured ECG and blood pressure in 10 755 subjects at baseline. The Cornell product (CP) and Sokolow-Lyon (SL) voltage were calculated as markers of LVH (CP >or=2440 mm x ms and SL voltage >or=38 mm). Follow-up was performed for 10 years, and the incidence of stroke and myocardial infarction was evaluated. The prevalence of CP-LVH was 2.7% for normotensives, 5.2% for prehypertensives, and 11.0% for hypertensives, and the prevalence of SL-LVH was 5.0%, 8.2%, and 15.2%, respectively. In all of the subjects, CP-LVH and SL-LVH were both predictors of stroke (CP-LVH: hazard risk: 1.62, 95% CI: 1.19 to 2.20, P=0.002; SL-LVH: hazard risk: 1.29, 95% CI: 0.98 to 1.71, P=0.07) after adjustment for confounding factors but were not predictors of myocardial infarction. The adjusted hazard ratio of CP-LVH predicting stroke was especially high in the normotensives (hazard risk: 7.53; 95% CI: 3.39 to 16.77). In the normotensives, diabetes mellitus and hyperlipidemia were significant determinants of CP-LVH but not of SL-LVH. In all of the hypertensive subgroups (normotensives, prehypertensives, and hypertensives), the c-statistic for the equation predicting stroke increased when CP-LVH was added to the model but not when SL-LVH was added. In conclusion, both CP-LVH and SL-LVH are risk factors for stroke in the Japanese general population. CP-LVH is related to glucose abnormality, and its predictive value for stroke is seen even in normotensives and prehypertensives.

Different BMI cardiovascular risk thresholds as markers of organ damage and metabolic syndrome in primary hypertension

Obesity is the main intermediate phenotype of primary hypertension (PH), and increased fat mass is directly related to target organ damage (TOD) and metabolic syndrome (MS). The aim of the study was to assess the sensitivity and specificity of body mass index (BMI), percentile-based, definitions of obesity [BMI > 95th percentile (pc)], and overweight (BMI > 85th pc), and BMI thresholds for cardiovascular (cv) complications (BMIcv) described by Katzmarzyk et al. (Pediatrics 114:198-205, 2004) in predicting risk of TOD and MS in 122 adolescents with PH. Our results indicated that the prevalence of left ventricular hypertrophy (LVH) and carotid intima-media thickness (cIMT) above 2 standard deviations (SDS) was the same, irrespective of the criteria used. BMIcv was more sensitive as a marker of LVH than were the cut-off values of the 85th pc and 95th pc of BMI (87.5%, 75%, 62.5%, respectively; P < 0.0001). BMIcv thresholds and cut-off values of the 85th pc of BMI were of the same sensitivity in predicting the presence of MS (95.8% and 95.8%, respectively) and were more sensitive than the cut-off values of the BMI 95th pc (87.5%; P = 0.02). Metabolic abnormalities, including insulin resistance, were more marked in patients with greater BMI, irrespective of cut-off value. However, only when a stratification system using the 85th pc of BMI was used, were the differences significant for a homoeostasis model assessment for insulin resistance (HOMA-IR) and for serum concentrations of high-density lipoprotein (HDL)-cholesterol, triglycerides and adiponectin. We concluded that BMIcv is more sensitive for diagnosing the presence of LVH and that the cut-off value of the 85th pc of BMI is more sensitive for predicting presence of MS in children with PH.

Prevalence of left ventricular hypertrophy detected by Cornell voltage‐duration product in a hypertensive population

Introduction. Detection and treatment of left ventricular hypertrophy (LVH) in hypertension is important in order to reduce cardiovascular risk. The product of QRS voltage and duration (e.g. Cornell voltage‐duration product; CorP), is a good marker of LVH and the current study was designed to determine the prevalence of LVH in patients with essential hypertension treated in general practice. Methods. This study was a multicenter, cross‐sectional survey in outpatient hypertensive patients attending clinics across Spain. The primary endpoint for detection of LVH was a CorP >2.440 mm·ms on ECG recordings, which were independently assessed. Results. Seven hundred and eighty‐two patients were evaluated (66.1±10.4 years; 50.6% males; body mass index 28.2±6.1 kg/m2) with a mean baseline blood pressure (BP) of 155.7±17.7/90.8±10.6 mmHg. Only 13.2% of the study population had BP that was adequately controlled. LVH was detected in 23.4% of patients using the CorP method. Predictors of LVH were prior history of LVH, hypertensive retinopathy, age, grade II hypertension and male gender. Conclusions. Almost one‐quarter of hypertensive patients who attended outpatient clinics in Spain had LVH detected by CorP. The CorP criterion appears to be a useful method for detecting LVH in general practice.

Abstract 1936: Cornell Product Left Ventricular Hypertrophy In Electrocardiogram Is A Strong Predictor Of Stroke In Community-dwelling Japanese Normotensives

Background : Incidence of stroke is higher than ischemic heart disease in Japanese. Left ventricular hypertrophy (LVH) is associated with an increased risk for stroke among hypertensives. We evaluated the risk of LVH among normotensives (SBP/DBP&lt;120/80 mmHg) subjects. Methods: In a Japanese general population, 10755 subjects who were undertaken electrocardiogram and measured BP at baseline were evaluated Cornell product (CP) and Sokolow-Lyon (SL) voltage as markers of LVH (CP≥2440 mm ms and SL voltage&gt;35 mm). Follow-up was performed for 10 years and incidence of stroke was evaluated. Results: Prevalence of CP-LVH were 2.7% for normotensives, 5.2 % for prehypertensives, 11.0 % for hypertensives, and that of SL-LVH were 8.6%, 11.4%, and 22.5%, respectively. In overall subjects, CP-LVH and SL-LVH were independent predictors of stroke [CP-LVH: hazard risk (HR) 1.65, 95% confidence interval (CI) 1.22–2.25, SL-LVH: HR 1.30, 95%CI 1.02–1.65] after adjustment for confounding factors. In Cox regression analysis in each stage of hypertension, hazard ratios of stroke in subjects with CP-LVH were higher among normotensives (HR 8.28, 95%CI 3.72–18.41) than among prehypertensives (HR 1.56, 95%CI 0.67–3.63) and hypertensives (HR 1.48, 95%CI 1.02–2.13) (Figure ), although that in subjects with SL-LVH were not significant (normotensives: HR 1.54, 95%CI 0.70–3.40, prehypertensives: HR 1.29, 95%CI 0.72–2.32, hypertensives: HR 1.21, 95%CI 0.90–1.62). Conclusion: The ECG-LVH independently predicted future stroke in a Japanese general population. The specificity of the Cornell product-LVH is higher than that of Sokolow-Lyon-LVH especially among normotensive subjects &lt;120/80 mmHg.

Abstract 814: Atorvastatin Attenuates Oxidative Stress And Improves Neuronal Nitric Oxide Synthase In The Brain Stem Of Heart Failure Mice

3-Hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors (statins) have been shown to reduce the incidence of myocardial infarction independent of their lipid-lowering effects. Nitric oxide (NO) in the central nervous system contributes to cardiovascular regulatory mechanisms. Imbalance between nitric oxide (NO) and superoxide anion (O 2 . − ) in the brain may contribute to enhanced sympathetic drive in heart failure (HF). This study was done to determine whether treatment with atorvastatin (ATS) ameliorates the imbalance between NO and O 2 . − production in the brain stem and contributes to improvement of left ventricular (LV) function. Methods and Results: Myocardial infarction (MI) was induced by ligation of the left coronary artery or sham surgery. Subsequently, mice were treated with ATS (10 μg/kg) (MI + ATS), or vehicle (MI + V). After 5 weeks, echocardiography revealed left ventricular dilatation in MI mice. Realtime RT-PCR indicated an increase in the mRNA expression of the LV hypertrophy markers, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Neuronal NOS (nNOS) and endothelial NOS (eNOS) mRNA expression were significantly reduced, while that of NAD(P)H oxidase subunit (gp91phox) expression was elevated in the brain stem of MI mice. Compared with sham-operated mice, ATS-treated mice showed reduced cardiac dilatation, decreased ANP and BNP in the LV. ATS also reduced gp91phox expression and increased nNOS mRNA expression in the brain stem, while no changes in eNOS and iNOS were observed. Conclusion: These findings suggest that ATS reduces oxidative stress and increases neuronal NOS in the brain stem, and improves left ventricular function in heart failure.

NT-proBNP changes, oxidative stress, and energy status of hypertrophic myocardium following ischemia/reperfusion injury

N-terminal pro-B-type natriuretic peptide (NT-proBNP) is a sensitive functional marker in heart disease, including left ventricular hypertrophy (LVH) secondary to valvular aortic stenosis (AS). We evaluated the association between NT-proBNP changes, oxidative stress, energy status and severity of LVH in patients with AS. Ten patients undergoing aortic valve replacement for AS were studied. Plasma NT-proBNP concentrations were performed by electroluminescence immunoassay 15 min after the induction of anesthesia (t0), before aortic cross-clamping (t1), before clamp removal (t2), 15 min after myocardial reperfusion (t3), and 24 h after surgery (t4). Heart biopsies were obtained and high energy phosphates (ATP, ADP, AMP) were analyzed by capillary electrophoresis (CE). In plasma samples from the coronary sinus, nitrate plus nitrite (NOx) concentrations were also analyzed by CE. Echocardiographic measurements were acquired and correlations between biochemical markers and severity of AS were assessed. NT-proBNP peaked significantly at t4 ( p < 0.001). A linear correlation between NT-proBNP values measured at t0 and t4 was found ( R 2 = 0.89; p < 0.001). A negative correlation between NT-proBNP production and phosphorylation potential (ATP/ADP ratio) was observed ( R 2 = 0.62; p < 0.01). NOx values positively correlated with NT-proBNP levels ( p < 0.01). NT-proBNP inversely correlated with aortic valvular area ( r = 81, p < 0.01), positively correlated with mean ( r = 0.82, p < 0.01) and maximum left ventricle-to-aortic gradients ( r = 0.80, p < 0.01), and with left ventricular mass ( r = 0.69, p < 0.01). NT-proBNP is a useful marker of LVH and severity of AS. It may complement echocardiographic evaluation of patients with AS in identifying the optimum time for surgery.

High-Density Lipoprotein Cholesterol and Insulin Resistance Are Independent and Additive Markers of Left Ventricular Hypertrophy in Essential Hypertension

We examined whether plasma high-density lipoprotein-cholesterol (HDL-C) levels and glucose metabolism parameters are independent or additive predictors of left ventricular hypertrophy (LVH) in patients with untreated essential hypertension. The study group consisted of 41 Japanese patients with untreated essential hypertension and LVH (left ventricular mass index [LVMI] >125 g/m2; age 58+/-6 years, mean+/-SD), and the control group consisted of 39 age-matched patients with untreated essential hypertension without LVH (LVMI <or=125 g/m2; age 58+/-7 years). The following metabolic parameters were higher in the group with LVH: fasting plasma glucose (FPG) (p<0.01), fasting insulin concentration (F-IRI) (p<0.0001), and homeostasis model assessment (HOMA)-index (p<0.0001). Among the laboratory parameters investigated, plasma HDL-C levels were lower (p<0.0001), and triglyceride and uric acid levels were higher in the group with LVH (p<0.05 for both). The nighttime systolic and diastolic ambulatory blood pressure (ABP) (p<0.0001, p<0.01, respectively) and nighttime heart rate (p<0.01) were higher in patients with LVH. Multivariate logistic analysis identified HDL-C (odds ratio [OR]=0.92, 95% confidence interval [CI]=0.87-0.98, p<0.05), HOMA-index (OR=3.83, 95% CI=1.28-11.5, p<0.05) and nighttime systolic ambulatory blood pressure (ABP) (OR=1.06, 95% CI=1.00-1.13, p<0.05) as independent significant risk factors for LVH. Our findings suggest that HDL-C, HOMA-index and nighttime systolic ABP are independent predictors for the presence of LVH in Japanese patients with essential hypertension.

Digesting the Remodeled Heart

Of the many proteinases present in the myocardium, members of the matrix metalloproteinase (MMP) family have received most attention. However, the cysteine proteases and their inhibitors have now been implicated in the pathogenesis of cardiac remodeling in the hypertrophied and failing heart. Cathepsins, cysteine proteases of the papain family, are optimally active in the acidic pH of lysosomes and are responsible for the physiological digestive turnover of cellular molecules and organelles. We now know that the levels of cathepsins and their endogenous inhibitors, cystatins, can be regulated by a number of signaling molecules, and cathepsins can be released from lysosomes into the extracellular space. Cysteine proteinases may degrade extracellular matrix proteins, such as elastin and fibrillar collagens.1 Nonlysosomal cathepsin targets include degradation of matrix and bone via elastinolytic/collagenolytic activity, activation of pro-MMP, induction of anoikis-dependent apoptosis via matrix degradation, activation of caspases, and cleavage of focal adhesion kinases. A decade ago, measurement of cathepsin activity in heart tissue of different pathologies was used as a measure of lysosomal activity and …

Importance of the Electrocardiographic Strain Pattern in Patients With Resistant Hypertension

The electrocardiographic strain pattern is a marker of left ventricular hypertrophy and adverse cardiovascular prognosis. The objective of this study was to assess the factors associated with the presence of ECG strain in patients with resistant hypertension and, specifically, to evaluate the relationships between strain and left ventricular mass (LVM) and structure. In a cross-sectional design, 440 resistant hypertensive subjects were evaluated. Clinical, laboratory, electrocardiographic, 24-hour ambulatory blood pressures, and echocardiographic variables were obtained. Statistical analysis involved bivariate tests, analysis of covariance, and multivariate logistic regression. An ECG strain pattern was present in 101 patients (23%). Patients with strain were more frequently men with lower body mass index, had more target-organ damage, higher 24-hour blood pressure, higher serum creatinine and 24-hour microalbuminuria, and more prolonged QT interval duration than those without strain. After controlling for all covariates, the presence of strain remained associated with increased LVM and wall thicknesses, both in all patients and also in those with echocardiographic left ventricular hypertrophy. Furthermore, the presence of ECG strain was associated with increased LVM (P<0.001), higher 24-hour systolic blood pressure (P<0.001), prolonged maximum QTc-interval duration (P<0.001), lower waist circumference (P=0.009), male gender (P=0.011), physical inactivity (P=0.020), higher serum creatinine (P=0.031) and fasting glycemia (P=0.027), and the presence of coronary heart disease (P=0.001) and peripheral arterial disease (P=0.045). Thus, in resistant hypertension patients, the presence of ECG strain is independently associated with increased left ventricular wall thicknesses and mass and also with other potentially adverse factors. These relationships offer insight into the known association between strain and unfavorable cardiovascular prognosis.

Association between Electrocardiographic Left Ventricular Hypertrophy with Strain Pattern and Left Ventricular Structure and Function

Background and Purpose: Electrocardiographic left ventricular hypertrophy (LVH) with strain pattern has been documented as a marker for LVH. Its presence on the ECG of hypertensive patients is associated with poor prognosis. The study was carried out to assess the association of the electrocardiographic strain with left ventricular mass (LVM) and function in hypertensive Nigerians. Material and Methods: ECG as well as echocardiograms were performed in 64 hypertensive patients with ECG-LVH and strain pattern, 65 patients with ECG-LVH by Sokolow-Lyon (SL) voltage criteria and 62 normal controls. Results: The study showed that electrocardiographic left ventricular (LV) strain pattern is associated with dilated left atrium, larger LV internal dimensions and greater absolute and indexed LVM in hypertensive Nigerians compared with ECG-LVH by SL voltage criteria alone or normal controls. Conclusion: The findings of this study support the fact that the ECG strain pattern is associated with increased LVM and an increased risk of developing abnormal LV geometry.

N-Terminal Pro-B-Type Natriuretic Peptide and Echocardiographic Abnormalities in Severely Obese Patients: Correlation with Visceral Fat

B-Type natriuretic peptide (BNP) and its co-released peptide N-terminal propeptide (NT-proBNP) are both secreted mainly by the left cardiac ventricle as a consequence of pressure overload and wall stretch. This situation often occurs in obesity, in which the amount of intraabdominal fat may worsen the severity of morphologic and dynamic cardiac abnormalities detectable by echocardiography (1). Many studies have confirmed NT-proBNP as a sensitive marker for left ventricular hypertrophy and/or asymptomatic left ventricular dysfunction (2)(3), and it is particularly reliable because of its high negative predictive value (4). To our knowledge, however, recent findings on the relationship between NT-proBNP and morphologic and dynamic cardiac abnormalities in obesity are still inconsistent and controversial. Rivera et al. (5) reported lower NT-proBNP concentrations in obese patients with heart failure compared with nonobese patients. Conversely, Hermann-Arnhof et al. (6) found that NT-proBNP concentrations were increased in obese individuals and were comparable to the values for New York Heart Association class I patients. Therefore, to gain further information on the …

Section 14: Managing Patients With Hypertension and Heart Failure

Section 14: Managing Patients With Hypertension and Heart Failure

Proteasome inhibition promotes regression of left ventricular hypertrophy

Background: Left ventricular hypertrophy (LVH) is a quiet epidemic in our society. Over 20 million people have LVH secondary to hypertension, valvular heart disease, and ischemic cardiomyopathies. Unfortunately, 15-20% of patients treated medically (ACE-inhibitors) or surgically (aortic valve replacement for aortic stenosis) will continue to have LVH. This group maintains a significantly higher risk of cardiovascular events compared to those with reduced or normal left ventricular mass. Nuclear factor kappa B (NFkB) is a ubiquitous transcription factor central to the injury response. Activation of NFkB is dependent upon degradation of its inhibitory protein by the proteosome. Experiments in transgenic mice have demonstrated an important role for NFkB in the development of LVH. The purpose of the current project is to evaluate a clinically accessible proteosome inhibitor on the development of murine LVH. We hypothesized that NFkB inhibition would prevent the development of LVH and promote its regression. Methods: We utilized a murine model of reversible hypertrophy by administering isoproterenol (ISO - 100 mg/kg) intraperitoneally for 7-14 days. Proteosome inhibitors have been tested in human trials of stroke, solid tumors, and multiple myeloma. We delivered the proteosome inhibitor, PS-519 (PS - 1mg/kg), both concurrently and after ISO treatment. LVH was quantified by three Methods: heart weight/body weight ratios, measurement of histologic sections, and transthoracic echocardiography (TTE). Groups were compared by analysis of variance with Bonferonni-Dunn post-hoc analysis set with 95% confidence intervals. Results: Seven days after receiving ISO, mice developed significant LVH as measured by heart weight ratios, histology, and TTE compared to control and vehicle animals. After withdrawal of ISO, animals were observed for an additional 7 days when it was observed that all 3 markers of LVH had resolved to the level of control. When administered concurrently, PS-519 prevented ISO-induced LVH at 7 days. As an additional step, ISO was given for 7 days in order to develop LVH and continued for an additional 7 days. PS-519 was then given from day 8-14 in order to determine its effect on mice with existing hypertrophy. The below graph depicts TTE data for left ventricular posterior wall thickness during diastole. PS-519 caused regression of the previously developed ISO-induced LVH (*ISO delivered for 14 days versus ISO for 14 days with PS-519 days 8-14, p<0.001). Conclusion: Isoproterenol administration and withdrawal reproducibly results in the development and subsequent regression of LVH. Not only did PS-519 inhibit the development of LVH, but it also promoted regression. These results demonstrate a potential role for proteosome inhibition as a novel and clinically accessible strategy for treating patients with a variety of LVH-associated cardiomyopathies.

Obesity and the electrocardiogram

Obesity is associated with a wide variety of electrocardiographic (ECG) abnormalities. Most of these reflect alterations in cardiac morphology. Some serve as markers of risk for sudden death. Key ECG abnormalities or alterations occurring with disproportionately high frequency in obese subjects include: leftward shifts of the P wave QRS and T wave axes, various changes in P wave morphology, low QRS voltage, various markers of left ventricular hypertrophy (particularly the Cornell voltage and product), T wave flattening in the inferior and lateral leads, lengthening of the corrected QT interval and prolonged QT interval duration. Alterations in the signal-averaged ECG and in heart rate variability may be arrhythmogenic. Cardiac arrhythmias have been described in obese subjects, but are often accompanied by left ventricular hypertrophy or the sleep apnea syndrome. Many of these ECG abnormalities are reversible with substantial weight loss. Thus, obesity is associated with a wide variety of ECG abnormalities, many of which are corrected by weight loss.

Electrocardiographic strain pattern and prediction of cardiovascular morbidity and mortality in hypertensive patients.

The ECG strain pattern of lateral ST depression and T-wave inversion is a marker for left ventricular hypertrophy (LVH) and adverse prognosis in population studies. However, whether ECG strain is an independent predictor of cardiovascular (CV) morbidity and mortality in the setting of aggressive antihypertensive therapy is unclear. ECGs were examined at study baseline in 8854 hypertensive patients with ECG LVH who were treated in a blinded manner with atenolol- or losartan-based regimens. Strain was defined by the presence of a downsloping convex ST segment with an inverted asymmetrical T wave opposite to the QRS axis in leads V5 and/or V6 and was present in 971 patients (11.0%). The Losartan Intervention For Endpoint reduction in hypertension (LIFE) study composite end point of CV death or nonfatal myocardial infarction or stroke occurred in 1035 patients (11.7%). In Cox analyses adjusting only for treatment effect, ECG strain was a significant predictor of CV death (hazard ratio [HR] 2.26, 95% confidence interval [CI] 1.78 to 2.86), fatal/nonfatal myocardial infarction (HR 2.16, 95% CI 1.67 to 2.80), fatal/nonfatal stroke (HR 1.76, 95% CI 1.39 to 2.21), and the composite CV end point (HR 1.99, 95% CI 1.70 to 2.33). After further adjusting for standard CV risk factors, baseline blood pressure, and severity of ECG LVH, ECG strain remained a significant predictor of CV mortality (HR 1.53, 95% CI 1.18 to 2.00), myocardial infarction (HR 1.55, 95% CI 1.16 to 2.06), and the composite CV end point (HR 1.33, 95% CI 1.11 to 1.59). Thus, ECG strain is a marker of increased CV risk in hypertensive patients in the setting of aggressive blood pressure lowering, independent of baseline severity of ECG LVH.

Glucose effectiveness is strongly related to left ventricular mass in subjects with stage I hypertension or high-normal blood pressure

Background Evidence suggests that “glucose effectiveness,” (SG) or the effect of glucose per se to enhance net glucose disposal, may be at least as important as the insulin sensitivity index (SI) in the assessment of glucose tolerance. Our objective was to study the relationship of SG and SI parameters to left ventricular mass in a group of untreated, nondiabetic, and nonobese subjects recently diagnosed with stage I or high-normal blood pressure (BP). Methods In this sample of subjects, among whom the expected prevalence of insulin resistance is low, we assessed SG and SI parameters using the intravenous glucose tolerance test and minimal model analysis. We also measured left ventricular mass (LVM) index and diastolic function by echocardiography. Results We observed a strong relationship between SG and LVM index ( r = −0.61, P < .0001). Patients with left ventricular hypertrophy (LVH) had lower SG than those without LVH (0.1114 ± 0.04 v 0.2088 ± 0.08 × 10 −1 · min −1, P < .001). In contrast, patients below the lowest quartile of the SG parameter distribution had higher LVM index (126.4 ± 23.1 v 94.8 ± 22.3 g/m 2, P < .001) and also had higher prevalence of LVH than the other patients ( P < .0001). The SI related only to diastolic dysfunction, suggesting that SG may be an earlier marker of LVH than SI in hypertension. Conclusion In this sample of nonobese and glucose-tolerant subjects with an early stage of hypertension, SG but not SI was related to LVM.