Effects Of Left Ventricular Hypertrophy Research Articles

The Targeted Role of SGLT2 Inhibitors in Patients with Diabetic Cardiomyopathy

Diabetic cardiomyopathy (DCM) is myocardial contractile dysfunction due to the clustered effects of left ventricular hypertrophy, fetal gene reactivation and lipid accumulation in cardiomyocytes. Structural and functional abnormalities of the myocardium, beyond the elicitation of ischemia or hypertension, have been emphasised and called diabetic cardiomyopathy

Effect Of Left Ventricular Hypertrophy On The Outcome Of Coronary Artery Bypass Grafting.

To evaluate the relationship between left ventricular hypertrophy (LVH) and coronary artery bypass grafting (CABG) procedure especially on the early outcome during the first 6 months following surgical intervention. This prospective cohort study included 82 patients with coronary artery disease indicating CABG. These patients were admitted, operated and followed -up in cardiothoracic surgery departmentsin the faculty of medicine, Kafrelsheikh university hospitals in the period from April 2019 till November 2021.The patients included in this study were divided into two groups according to presence or absence of left ventricular hypertrophy, Group I had 38 (46.34%) patients with LVH and Group 2 had 44 (53 .65%). patients without LVH. The time to regain mechanical activity waslonger (5.76±1.82) minutesin LVH patients(p <0.001). LVH group had a significantly longer period of mechanical ventilation 16.50±4.25 hours (p <0.001) compared to non LVH group which was 9.61±3.78 hours. Also, the mean duration of ICU stays in the LVH group compared to the non LVH group was 3.81±1.20 days versus 2.56±0.81 daysrespectively. The ICU follow up showed a statistically significant relationship of arrhythmias with LVH (p =0.022), infections (p =0.005) and wound infections (p<0.001). In patients undergoing CABG surgery, LVH has been associated with increased morbidity and poor outcome.

Transplant Outcomes in Hearts with Moderate to Severe Left Ventricular Hypertrophy After the 2018 OPTN/UNOS Allocation Changes

<h3>Purpose</h3> After the 2018 OPTN/UNOS heart transplant (HT) allocation changes, there has been an increase in graft ischemia time, a factor shown to worsen HT outcomes in recipients of hearts with left ventricular hypertrophy (LVH). We compare HT outcomes in moderate to severe LVH defined by left ventricular wall thickness ≥ 1.4cm and non-LVH hearts and determine if there were changes in LVH HT outcomes after 2018. <h3>Methods</h3> The UNOS database was queried for all HT recipients ages >18 from 2016 to 2020. Multi-organ transplants were excluded. Demographic, donor, and recipient information were compared between LVH and non-LVH hearts. The primary outcome was post-transplant survival with secondary outcomes of rejection, cardiac allograft vasculopathy (CAV), and post-transplant ejection fraction, all at one year. Comparisons were made using Chi-squared and Wilcoxon rank-sum. Multiple logistic and linear regression models were used to discern the predictors of survival and the effect of LVH on outcomes. <h3>Results</h3> 10,175 HTs were analyzed: 491 LVH and 9784 non-LVH. After the 2018 changes, compared to non-LVH HT donors, LVH HT donors were older, had higher BMI, more often had HTN, were male, and had kidney disease. LVH HT recipients were older, higher BMI, and had greater HLA mismatch. Graft ischemia time, survival, and secondary outcomes were similar. Examining the LVH cohort specifically before and after the 2018 changes, there were no differences in survival or most secondary outcomes (decrease in CAV) despite increases in recipient BMI, recipient prior cardiac surgery, and graft ischemia time, which were independent predictors of worse outcomes in the overall cohort. LVH was not a predictor of survival or any secondary outcome. <h3>Conclusion</h3> Outcomes for recipients of hearts with moderate to severe LVH were not negatively impacted by the 2018 OPTN/UNOS changes despite longer graft ischemia time, and outcomes for recipients of LVH hearts were similar to those receiving hearts without LVH.

Exploration of electrocardiographic and echocardiographic findings to screen transthyretin amyloid cardiomyopathy in patients with mild left ventricular hypertrophy

Abstract Background The transthyretin amyloid cardiomyopathy (ATTR-CM), a common condition in the elderly, is a life-threatening disease; however, it is treatable. The early accurate diagnosis is, therefore, an important key to improve the patient's outcomes. Electrocardiography and echocardiography are instant diagnostic tools with red flags for the screening of the ATTR-CM. In fact, ATTR-CM often mimics left ventricular hypertrophy (LVH), and the differential diagnosis is difficult to establish. Thus, the characteristics of cardiac amyloidosis may be obscured in ATTR-CM patients with mild LVH, possibly making the disease difficult to diagnose. Therefore, in this study, the effect of LVH on the occurrence of electrocardiographic and echocardiographic parameters for ATTR-CM was investigated, and their incremental value over the age for the screening of ATTR-CM in the patients with mild LVH was recorded. Methods This study retrospectively studied 319 consecutive nonischemic LVH patients with a sinus rhythm who underwent detailed diagnostic tests. The light chain-associated amyloidosis was an exclusion criterion. The mean left ventricular wall thickness (MWT) &amp;lt;12 mm was defined as mild LVH, while MWT ≥12 mm was defined as moderate to severe LVH. The ATTR-CM was diagnosed with biopsy or 99 mTc-PYP scintigraphy. The elderly were defined as people aged ≥65 years in males and ≥70 years in females, according to the literature. Each electrocardiographic and echocardiographic parameter was binarized with an external cut-off point to increase the external validity, being the incremental benefit of each parameter over age for identifying ATTR-CM assessed using a receiver operating characteristic curve analysis and comparisons of the area under the curve (AUC). Results Fourteen patients (8%) among the 170 patients with mild LVH had ATTR-CM, while 27 patients (18%) among the 149 patients with moderate to severe LVH had ATTR-CM. The patients with mild LVH had fewer electrocardiographic and echocardiographic parameters, showing a significant difference between ATTR-CM and non-ATTR-CM patients than those with moderate to severe LVH (Table 1). Among several binarized parameters, the voltage-to-mass ratio, E/A ratio, the global longitudinal strain, and also the relative apical sparing pattern demonstrated additive value for identifying the ATTR-CM over aging (Table 2). In addition, the discriminative ability of the propensity score calculated from these four variables and age was considered excellent for the screening of ATTR-CM (AUC = 0.98). Conclusion The patients with mild LVH appear to have fewer electrocardiographic and echocardiographic specific findings of the ATTR-CM compared to patients with moderate to severe LVH. However, several red flags may be useful for screening ATTR-CM even in patients with a mild LVH. Funding Acknowledgement Type of funding sources: None. Table 1Table 2

OUTCOMES OF PATIENTS WITH ST SEGMENT ELEVATION MYOCARDIAL INFARCTION AND LEFT VENTRICULAR HYPERTROPHY: 25-YEAR POPULATION-BASED STUDY

Objective: Left ventricular hypertrophy is a common finding in hypertensive patients. The increase in myocardial masse is accompanied with an elevation of oxygen demand. The occlusion of a coronary artery in ST-segment elevation myocardial infarction (STEMI) leaves the myocardium without oxygen supply. This depletion is harmful to myocardial cells and its effect could be more important in left ventricular hypertrophy patients. Aim: To evaluate the effect of left ventricular hypertrophy on Stemi outcomes. Design and method: Patients with STEMI underwent an echocardiographic exam within two days from the event and left ventricular hypertrophy (LVH) was evaluated using the left ventricular mass calculated using echocardiography. The primary endpoints were in-hospital and 1-year cardiovascular events. The secondary endpoints were left ventricular ejection fraction. Results: In total, 1605 patients were admitted for STEMI. There were 489 hypertensive patients. 28% had LVH. There was no difference in risk-adjusted in-hospital mortality between patients with and without LVH (p = 0,149). Both groups showed the same risks of developing life threatening arrythmias (p = 0,287). Left ventricular ejection fraction was evaluated in both groups. Patients with LVH did not have more risk of systolic dysfunction than the other group of patients (p = 0,098). Conclusions: Patients with left ventricular hypertrophy undergoing STEMI had similar outcomes compared to patients without LVH.

Effects of Left Ventricular Hypertrophy and Myocardial Stiffness on Myocardial Strain Under Preserved Ejection Fraction.

Despite numerous experimental observations regarding heart failure with preserved ejection fraction (HFpEF), which is characterized mainly by left ventricular hypertrophy and a left ventricular ejection fraction over 50%, myocardial dynamics under HFpEF have not yet been fully clarified, particularly regarding the relationship between myocardial strain distribution and myocardial work. To address this issue, we numerically investigated radial distribution of myocardial strain during a cardiac cycle with fixed internal volume at the end of the systolic and diastolic phases under different mechanical conditions, such as those involving myocardial thickness and elasticity of myocardial fibers. The myocardium was a modeled as a visco-hyperelastic continuous material. This model was taken into account that active contractile stress along the myocardial fiber direction depends on membrane potential change. Our numerical results showed that both radial and circumferential strains decreased as wall thickness increased, which reflected cardiac hypertrophy, but that myocardial work became larger than that observed with thin ventricular walls. Further, the change in left ventricular diastolic internal pressure caused circumferential strain, while fiber stiffness contributed to radial strain. Since peak circumferential strain was well estimated by the maximum difference between total internal and myocardial volumes, measuring the epicardial contraction rate should be helpful in understanding patients with HFpEF.

Impact of left ventricular hypertrophy on myocardial injury in patients with ST-segment elevation myocardial infarction.

Left ventricular hypertrophy (LVH) has been suggested as a determinant of outcome in patients with ST-segment elevation myocardial infarction (STEMI). However, available data are inconclusive and the underlying mechanisms remain unclear. Therefore, the aim of this study was to evaluate the impact of LVH on myocardial injury and clinical outcome in a large multicenter STEMI population. Cardiovascular magnetic resonance was performed in 795 patients within 10days after STEMI to assess left ventricular (LV) mass and parameters of myocardial injury. Gender-specific cutoff values of indexed LV mass were used to define LVH (67g/m2 for men and 61g/m2 for women). Rates of major adverse cardiac events (MACE) were determined at 12-month follow-up. LVH was present in 438 patients (55%) and associated with a significantly larger infarct size [18.3% of LV mass (%LV) versus 14.0%LV; p < 0.01], a lower myocardial salvage index (47.8 versus 54.4; p < 0.01), larger extent of microvascular obstruction (0.4 versus 0%LV; p < 0.01) and lower LV ejection fraction (47.9 versus 53.2%; p < 0.01) compared to STEMI patients without LVH. The effect of LVH on LV ejection fraction, infarct size and myocardial salvage index remained statistically significant after adjustment for baseline characteristics (p < 0.01 for all). MACE rates at 12 months were numerically higher in patients with versus without LVH without reaching statistical significance (7.5 versus 5.6%; p = 0.32). In STEMI patients, LVH is associated with more pronounced structural and functional alterations in CMR imaging as an indicator for adverse clinical outcomes in STEMI survivors.

Effect of left ventricular hypertrophy and deformation on cardiac function in patients with uremia cardiomyopathy by using quantitative speckle tracking technology

To evaluate the effect of left ventricular hypertrophy and deformation on cardiac function in patients with uremic cardiomyopathy (UCM) by using the technology of two dimensional speckle tracking imaging (2D-STI). Methods: A total of 67 UCM patients were randomly divided into the normal cardiac function group (subgroup A, 32 cases) and the abnormal cardiac function group (subgroup B, 35 cases) according to the New York Heart Association points (NYHA-P). A total of 30 healthy subjetcs served as the control group. Parameters including left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular spherical index (LVSI), left ventricular myocardial mean radial strain (MRS), mean radial strain rate (MRSR), mean longitudinal strain (MLS), local systolic twist angle (STA), and mitral annulus maximum displacement (TMAD) were detected. Results: MLS, MRS, MRSR, LVSI, STA and TMAD in the Group A and Group B were lower than that in the control group (P<0.05), and LVMI in the Group A and Group B was increased than those in the control group (P<0.05); LVEF, MLS, MRS, MRSR, LVSI and STA in the Group B was decreased than that in the Group A (P<0.05). MLS in the Group A and B were positively correlated with LVEF and LVSI, but negatively correlated with LVMI. Using the point of 14.10% for MLS to evaluate UCM patients with NYHA-P>4 points, the sensitivity, the specificity and Yuedden index were 90.5%, 71% and 0.585, respectively. STA in UCM patients were lower than that in the control (P<0.05). Conclusion: 2D-STI possesses a unique advantage in detecting left ventricular strain and strain rate on left ventricular regional function in UCM with left ventricular hypertrophy and ventricular deformation. There is no direct correlation between the left ventricular hypertrophy and ventricular deformation, but the ventricular hypertrophy and deformation are correlated with regional cardiac function and clinical cardiac function. Left ventricular regional dysfunction may occur before cardiac hypertrophy and deformation.

QRS complex waveform indicators of ventricular activation slowing: Simulation studies

Diffuse or regional activation slowing in ventricular myocardium can result from different cardiac pathologies, such as left ventricular hypertrophy, ischemia or fibrosis. Altered ventricular activation sequence leads to deformations of the activation front and consequently to the changes in the QRS complex. Using a computer model we simulated the effect of slowed ventricular activation on the QRS waveform with a special interest in ECG changes which reproduce the ECG criteria of left ventricular hypertrophy (ECG-LVH). This paper describes results of a set of computer modeling experiments and discusses visual QRS patterns. Slowed ventricular activation in the whole left ventricle resulted in the prolongation of QRS duration, leftward shift of electrical axis, and increase in the QRS amplitude mainly in the precordial leads, having thus their main impact on simulated Sokolow–Lyon index and Cornell voltage. Slowed ventricular activation in the anteroseptal region resulted in a leftward shift of the electrical axis and increased values of ECG-LVH criteria seen in limb leads or in a combination with precordial leads (Gubner criterion, Cornell voltage). Transmural slowing and midwall slowing in two layers in the anteroseptal area led also to the QRS duration prolongation. Changes in QRS complex were more pronounced in the cases of transmural slowing as compared to the left ventricular midwall slowing. Using computer modeling, we showed that slowed ventricular activation is a potent determinant of QRS complex morphology and can mimic ECG patterns that are usually interpreted as the effect of left ventricular hypertrophy, i.e., increased left ventricular mass. These results contribute to understanding the variety of ECG finding documented in patients with LVH, considering not only anatomical enlargement but also the altered electrical properties of hypertrophied myocardium.

The effect of conduction velocity slowing in left ventricular midwall on the QRS complex morphology: A simulation study

Midwall fibrosis is a frequent finding in different types of left ventricular hypertrophy. Fibrosis presents a local conduction block that can create a substrate for ventricular arrhythmias and lead to the continuous generation of reentry. Having also impact on the sequence of ventricular activation it can modify the shape of QRS complex. In this study we simulated the effects of slowed conduction velocity in the midwall in the left ventricle and in its anteroseptal region on the QRS morphology using a computer model. Material and methodsThe model defines the geometry of cardiac ventricles analytically as parts of ellipsoids; the left ventricular wall is represented by five layers. The impulse propagation velocity was decreased by 50% in one and two midwall layers, respectively, in the whole left ventricle and in LV anterior region. The effects of slowed conduction velocity on the QRS complex of the 12-lead electrocardiogram are presented as 12-lead electrocardiograms and corresponding values of ECG criteria for left ventricular hypertrophy (ECG-LVH criteria): Gubner criterion, Sokolow–Lyon index (SLI) and Cornell voltage. ResultsAll simulated situations led to increased R wave amplitude in the lead I and of S wave in the lead III, showing a leftward shift of the electrical axis and increased values of ECG-LVH criteria based on limb leads alone or in combination with precordial leads (Gubner criterion, Cornell voltage). The slowed conduction velocity in the whole LV influenced the QRS complex voltage in precordial leads, having an impact on the SLI and Cornell voltage. The changes were pronounced if two layers were involved. ConclusionUsing computer modeling we showed that the midwall slowing in conduction velocity modified the QRS complex morphology. The QRS complex changes were consistent with ECG-LVH criteria, i.e. QRS patterns usually interpreted as the effect of left ventricular hypertrophy (the increased left ventricular mass).

Relationship of MTHFR gene polymorphisms with renal and cardiac disease.

To investigate the effects of different methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism and hyperhomocysteinemia for the development of renal failure and cardiovascular events, which are controversial. We challenged the relationship, if any, of MTHFR 677C>T and MTHFR 1298A>C polymorphisms with renal and heart function. The present article is a reappraisal of these concepts, investigating within a larger population, and including a subgroup of dialysis patients, if the two most common MTHFR polymorphisms, C677T and A1298C, as homozygous, heterozygous or with a compound heterozygous state, show different association with chronic renal failure requiring hemodialysis. MTHFR polymorphism could be a favorable evolutionary factor, i.e., a protective factor for many ominous conditions, like cancer and renal failure. A similar finding was reported in fatty liver disease in which it is suggested that MTHFR polymorphisms could have maintained and maintain their persistence by an heterozygosis advantage mechanism. We studied a total of 630 Italian Caucasian subject aged 54.60 ± 16.35 years, addressing to the increased hazard of hemodialysis, if any, according to the studied MTHFR genetic polymorphisms. A favorable association with normal renal function of MTHFR polymorphisms, and notably of MTHFR C677T is present independently of the negative effects of left ventricular hypertrophy, increased Intra-Renal arterial Resistance and hyperparathyroidism. MTHFR gene polymorphisms could have a protective role on renal function as suggested by their lower frequency among our dialysis patients in end-stage renal failure; differently, the association with left ventricular hypertrophy and reduced left ventricular relaxation suggest some type of indirect, or concurrent mechanism.

Increased mobilization of mesenchymal stem cells in patients with essential hypertension: the effect of left ventricular hypertrophy.

Stem cells have great clinical significance in many cardiovascular diseases. However, there are limited data regarding the involvement of mesenchymal stem cells (MSCs) in the pathophysiology of arterial hypertension. The aim of this study was to investigate the circulation of MSCs in patients with essential hypertension. The authors included 24 patients with untreated essential hypertension and 19 healthy individuals. Using flow cytometry, MSCs in peripheral blood, as a population of CD45-/CD34-/CD90+ cells and also as a population of CD45-/CD34-/CD105+ cells, were measured. The resulting counts were translated into the percentage of MSCs in the total cells. Hypertensive patients were shown to have increased circulating CD45-/CD34-/CD90+ compared with controls (0.0069%±0.012% compared with 0.00085%±0.0015%, respectively; P=.039). No significant difference in circulating CD45-/CD34-/CD105+ cells was found between hypertensive patients' and normotensive patients' peripheral blood (0.018%±0.013% compared with 0.015%±0.014%, respectively; P=.53). Notably, CD45-/CD34-/CD90+ circulating cells were positively correlated with left ventricular mass index (LVMI) (r=0.516, P<.001). Patients with essential hypertension have increased circulating MSCs compared with normotensive patients, and the number of MSCs is correlated with LVMI. These findings contribute to the understanding of the pathophysiology of hypertension and might suggest a future therapeutic target.

The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation

The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation

PM066 The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation

PM066 The Effect of Left Ventricular Hypertrophy and Associated Diastolic Dysfunction on Left Ventricular Remodeling and Exercise Capacity in a Murine Model of Mitral Regurgitation

Renal Insufficiency in Non-Diabetic Subjects: Relationship of MTHFR C677t Gene Polymorphism and Left Ventricular Hypertrophy

Background: Association of methylenetetrahydrofolate reductase (MTHFR) 677C>T gene polymorphism with hyperhomocysteinemia, renal failure, and cardiovascular events is controversial. We investigated the relationship of MTHFR 677C>T polymorphisms with left ventricular hypertrophy (LVH) and renal insufficiency. Methods: Glomerular filtration rate (GFR) and left myocardial ventricular mass/m2 were assessed in 138 non-diabetic subjects (age, 50.93 ± 14.85 years; body mass index, 27.95 ± 5.98 kg/m2), 38 no-mutation wild MTHFR C677CC, 52 heterozygous MTHFR C677CT, and 48 homozygous MTHFR C677TT, all with adequate adherence to current international healthy dietary guidelines. Serum homocysteine, insulin resistance, high-sensitivity C-reactive-protein (hsCRP), parathyroid hormone, and renal artery resistive index (RRI) were challenged by odds ratio analysis and multiple linear regression models. Results: MTHFR 677C>T polymorphism showed higher GFR (73.8 ± 27.99 vs. 58.64 ± 29.95; p= 0.001) and lower renal failure odds (OR, 0.443; 95% confidence interval, 0.141–1.387) in comparison with wild MTHFR genotype. A favorable effect on GFR of MTHFR polymorphism is presented independently by the negative effects of LVH, increased intra-renal arterial resistance, and hyperparathyroidism; GFR is the significant predictive factor to LVH. Conclusions: Renal insufficiency in non-diabetic subjects is explained by interactions of MTHFR C677T polymorphism mutation with LVH, hsCRP, intact parathyroid hormone (iPTH), and RRI. Sign of these predictive effects is opposite: subjects with MTHFR 677C>T polymorphism have lower likelihood of renal insufficiency; differently, wild-type MTHFR genotype subjects have lower GFR and greater hsCRP, iPTH, RRI, and LVH.

Relationship of Multidirectional Myocardial Strain with Radial Thickening and Ejection Fraction and Impact of Left Ventricular Hypertrophy: A Study in a Community‐Based Cohort

Left ventricular (LV) systolic strain provides additional prognostic value to LV ejection fraction (LVEF) and wall motion analysis. However, the relationship between myocardial multidirectional strain and LVEF, and the effect of LV hypertrophy on this relationship, are not completely understood especially in unselected populations. LV global longitudinal (εL ) and circumferential (εC ) systolic strain analysis was performed by two-dimensional speckle tracking echocardiography in 215 participants from a community-based study. LV radial wall thickening was measured as global radial strain (εR ), and LVEF was assessed by biplane Simpson's method. εR was significantly associated with εC (β = -0.56, P < 0.01) and with εL (β = -0.18, P < 0.01). The contribution of εL to εR was especially evident in subjects with lower εC and in presence of LV hypertrophy (β = -0.30, P < 0.01). εL and εC were significantly associated with LVEF (β = -0.36 and β = -0.49, both P < 0.01) independent of LV mass and other confounders, and their interaction significantly improved the prediction of LVEF (R(2) -change = 0.14) but not of εR (R(2) -change = 0.002). εR is mainly related to εC with a smaller contribution of εL , which becomes especially evident in subjects with lower εC and in presence of LV hypertrophy. Therefore, radial thickening may not detect subclinical LV longitudinal function reduction in normal ventricles and when εC is preserved. While a reduction in εL has a limited impact on εR , it exerts a greater effect on global LVEF, therefore for a more accurate LVEF prediction both εL and εC need to be considered.

The Association of Left Ventricular Hypertrophy with Intraventricular Dyssynchrony at Rest and during Exercise in Hypertensive Patients

BackgroundImpaired exercise tolerance with dyspnea is common in hypertensive patients and this may be due to the exaggeration of nonuniform ventricular activation during exercise. So we want to evaluate the effect of left ventricular hypertrophy (LVH) on systolic intraventricular dyssynchrony during exercise.MethodsA total of 85 patients with hypertension who having exertional dyspnea and 30 control individuals were enrolled. Exercise stress echocardiography was performed using a symptom limited, multistage supine bicycle test. To evaluate the dyssynchrony of left ventricular (LV), we calculated the standard deviation (SD) of the averaged time-to-peak systolic velocity (TPs-SD, ms) of 12 middle and basal LV segments obtained from the three standard apical views at rest and peak exercise.ResultsThere was no significant difference in systolic blood pressure (BP) and heart rate between the two groups. TPs-SD was significantly higher in patients with LVH at rest (31.5 ± 12.1 vs. 22.0 ± 12.6 ms, p = 0.002) with exaggeration of the degree at peak exercise (39.0 ± 11.9 vs. 24.6 ± 13.3 ms, p < 0.001). Multiple regression analysis showed LV mass index was independently associated with LV dyssynchrony at peak exercise (β = 0.515, p = 0.001) when controlled for age, sex, and systolic BP at peak exercise.ConclusionIntraventricular systolic dyssynchrony during exercise is significantly associated with the degree of LVH in hypertensive patients.

Multiplex Analysis of Cardiac Hypertrophic Signaling: Reduced in vivo Phosphorylation of Glycogen Synthase Kinase-3&#946; and Proline-Rich Akt Substrate (PRAS40)

The serine/threonine kinase Akt (PKB) is activated in response to growth factors, cytokines and other growth promoting stimuli and is involved in the regulation of a number of cellular processes including metabolism, cell growth, proliferation and survival. To study intracellular metabolic effects of left ventricular hypertrophy (LVH) induced by chronic aortic banding in a recently established swine model, protein arrays can be used to analyze changes in cytosolic protein phosphorylation levels such as cell signal transduction and protein kinase pathways. Miniaturized sandwich immunoassays allow the simultaneous analysis of several parameters in a single experiment. Bead-based protein array systems or suspension microarrays are well-established multiplex sandwich immunoassay formats. Cytosolic proteins were extracted from pig hearts. Using the bead-based Luminex system, multiplexed sandwich immunoassays have been developed to analyze the phosphorylated proteins IR[pYpY1162/1163], IGF-1R[pYpY1135 /1136], IRS-1[pS312], Akt[pS473], PRAS40[pT246], p70S6K[pTpS421/424], and GSK-3β[pS9], which were measured simultaneously in extracted myocardial tissue homogenates with the Akt Pathway Phospho 7-Plex Panel using a Luminex 100 IS system. Using this assay, tissue homogenates derived from myocardial tissue samples from 28 individual porcine in vivo model experiments in normal hearts (n=17) and LVH hearts (n=11) were analyzed for phosphorylated protein concentrations. Results obtained allowed grouping of myocardial tissue samples into a LVH and a normal group. Two candidate molecules: PRAS40 (normal vs. LVH two-tailed probability P= 0.0022) and GSK-3β (P=0.003), had lower concentrations in LVH pigs than in normal animals, suggesting loss of GSK-3β inhibitory activity and contributing to speculation of altered insulin sensitivity associated with LVH. Keywords: Cardiac hypertrophy, akt/protein kinase B, glycogen synthase (GSK)-3β, proline-rich akt substrate (PRAS40), multiplex analysis, animal model, phosphatidyli-nositol 3-kinase (PI3K) pathway, sandwich immunoassay flow cytometry, sevoflurane anesthesia, IR, IGF-1R, IRS-1, Akt, PRAS40, p70S6K, GSK-3, IR[pYpY1162/1163], IGF-1R[pYpY1135/1136], IRS-1[pS312], Akt[pS473], pT246, GSK-3[pS9], Ambulatory transthoracic ultrasound examinations

Is remodeling the dominant compensatory mechanism in both chronic heart failure with preserved and reduced left ventricular ejection fraction?

The mechanisms of heart failure are ill understood with multiple, heterogeneous hypotheses proposed to describe the condition. This study examines the individual effects of left ventricular hypertrophy, long-axis shortening and the effect of left ventricular remodeling on ejection fraction, end-diastolic volume and stroke volume using a mathematical model of left ventricular contraction. Reducing long-axis shortening caused a decline in stroke volume independently of hypertrophy. Increasing concentric left ventricular hypertrophy resulted in an increase in ejection fraction secondary to augmented wall thickening. A decline in stroke volume occurred despite a preserved ejection fraction when concentric hypertrophy was present. Normalization of stroke volume by remodeling resulted in a marked increase in end-diastolic volume in the absence of hypertrophy and an end-diastolic volume similar to normal in the presence of concentric hypertrophy. The model predicts that the dominant compensatory mechanism in chronic heart failure is remodeling with normalization of stroke volume. Observational data cited supports this conclusion.

Effect of Left Ventricular Hypertrophy on Long-Term Survival of Patients with Coronary Artery Disease following Percutaneous Coronary Intervention

The impact of left ventricular hypertrophy (LVH) on survival among patients with established coronary artery disease (CAD) is not well understood. We sought to evaluate the effect of LVH on the survival of patients with CAD following percutaneous coronary intervention (PCI). Three hospitals in New York City contributed prospectively defined data on 4284 consecutive patients undergoing PCI. Allcause mortality at a mean follow-up of three years was the primary endpoint. LVH was present in 383 patients (8.9%). LVH patients had a greater prevalence of hypertension (88% vs. 68%, p<0.001), vascular disease (21% vs. 6.6%, p=0.001), and prior heart failure (10% vs. 5.5%, p<0.001). LVH patients presented less often with one-vessel disease (38% vs. 50%, p=0.040) and more often with two- (34% vs. 29%, p=0.014) or three-vessel (22% vs. 18%, p=0.044) disease. Ejection fractions and angiographic success were similar in both groups. In-hospital mortality did not differ between groups. At three-year follow-up, the survival rate for patients with LVH was 86% vs. 91% in patients without LVH (log-rank p=0.001). However, after adjustment for differences in baseline characteristics using Cox proportional hazards analysis, LVH was found not to be an independent predictor of mortality (hazard ratio, 0.93; 95% confidence interval, 0.68–1.28; p=0.67). We conclude that LVH at the time of PCI is not independently associated with an increase in the hazard of death at three years.