Prognostic significance of NT-proBNP, 3D LA volume and LV dyssynchrony in patients with acute STEMI undergoing primary percutaneous intervention

Objectives

The aim of the present study was to assess the short term prognostic significance of N-terminal pro BNP (NT-proBNP), 3D left atrial volume (LAV) and left ventricular (LV) dyssynchrony in patients of acute ST-elevation myocardial infarction (STEMI) who underwent primary Percutaneous intervention (PCI).

Background

NT-proBNP, LV dyssynchrony and LAV in patients with acute coronary syndrome have been associated with PCI outcomes and predict the short and long-term prognosis.

Methods

This study consisted of 142 patients with a first STEMI who underwent primary PCI. Baseline echocardiographic data was collected at admission and at 6 months follow up. Left ventricular dyssynchrony was measured by tissue Doppler imaging and LAV by real time 3D-echocardiography, plasma NT-proBNP levels were estimated between 72 and 96 h of admission.

Results

During study period 3 patients expired and 4 developed congestive heart failure (CHF). Baseline NT-proBNP and LV dyssynchrony correlated with LV size and LV ejection fraction (LVEF) at baseline and during follow up. Patients with higher NT-proBNP levels and higher LV dyssynchrony showed significant increase in LV size with decrease in LVEF during follow-up. Baseline Left atrial volume index (LAVI) showed significant correlation with LV size but no association with LVEF at baseline and during follow-up.

Conclusions

Higher levels of NT-proBNP and higher LV dyssynchrony can predict patients with increase in LV size, worsening of LV systolic and diastolic function during follow-up. Patients with higher NT-proBNP levels at baseline developed CHF during follow-up.     

Recovery and recurrence of left ventricular systolic dysfunction in patients with idiopathic dilated cardiomyopathy

BACKGROUND:

Some patients with nonischemic left ventricular (LV) systolic failure recover to have normal LV systolic function. However, few studies on the rates of recovery and recurrence have been reported, and no definitive indicators that can predict the recurrence of LV dysfunction in recovered idiopathic dilated cardiomyopathy (IDCMP) patients have been determined. It was hypothesized that patients who recovered from nonischemic LV dysfunction have a substantial risk for recurrent heart failure.

METHODS:

Forty-two patients (32 men) with IDCMP (mean [± SD] age 56.9±8.7 years) who recovered from systolic heart failure (LV ejection fraction [LVEF] of 26.5±6.9% at initial presentation) to a near-normal state (LVEF of 40% or greater, and a 10% increase or greater in absolute value) were monitored for recurrence of LV systolic dysfunction. Patients with significant coronary artery disease were excluded. Patients were monitored for 41.0±26.3 months after recovery (LVEF 53.4±7.6%) from LV dysfunction.

RESULTS:

LV systolic dysfunction reappeared (LVEF 27.5±8.1%) during the follow-up period in eight of 42 patients (19.0%). No significant difference between the groups with or without recurrent heart failure was observed in the baseline clinical and echocardiographic characteristics. However, more patients in the recurred IDCMP group than those in the group that maintained the recovery state had discontinued antiheart failure medication (62.5% versus 5.9%, P<0.05).

CONCLUSIONS:

LV dysfunction recurs in some patients with reversible IDCMP. The recurrence was significantly correlated with the discontinuation of antiheart failure drugs. The results suggest that continuous medical therapy may be mandatory in patients who recover from LV systolic dysfunction.     

Detection of left ventricular asynchrony and its relationship with the Tei index in patients with coronary artery ectasia

OBJECTIVE:

To evaluate left ventricular (LV) systolic asynchrony and its relationship with the Tei index using tissue Doppler imaging (TDI); and to evaluate the relationship of thrombolysis in myocardial infarction frame count (TFC) and Tei index with LV asynchrony in patients with coronary artery ectasia (CAE).

METHODS:

A total of 50 CAE patients and 40 control subjects were evaluated. Diagnosis of CAE was made angiographically and TFC was calculated. LV systolic and diastolic function was assessed by conventional echocardiography and TDI. Evaluation of intra-LV systolic asynchrony was performed using tissue synchronization imaging (TSI).

RESULTS:

In patients with CAE, the Tei index was significantly higher than in controls (0.63±0.12 versus 0.52±0.12; P<0.001). LV systolic asynchrony parameters of TSI including SD of the peak tissue velocity (Ts) of the 12 LV segments (Ts-SD-12), maximal difference in Ts between any two of the 12 LV segments (Ts-12), SD of the Ts of the six basal LV segments (Ts-SD-6), maximal difference in Ts between any of the six basal LV segments (Ts-6) were significantly lengthened in patients with subclinical hypothyroidism compared with controls (P<0.001, P<0.001, P<0.001 and P<0.001, respectively). In addition, a positive correlation was found between Ts-SD-12 and the Tei index in patients with CAE (r=0.841; P<0.001) and mean TFC was positively correlated with Ts-SD-12 and the Tei index (r=0.345; P=0.013 and r=0.291; P=0.021, respectively).

CONCLUSION:

Patients with CAE exhibit evidence of LV systolic asynchrony according to TSI. LV systolic asynchrony is related to the Tei index and mean TFC. Furthermore, the Tei index is an independent risk factor for LV systolic asynchrony.     

Effects of low-dose hydroxychloroquine on expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in peri-infarct myocardium in rats

BACKGROUND:

Low-dose hydroxychloroquine (HCQ) and ataxia-telangiectasia-mutated (ATM) protein kinase have recently been postulated to be beneficial for the prevention of the age-associated metabolic syndrome including hypertension, hypercholesterolemia and glucose intolerance; however, the effects of low-dose HCQ on the expression of ATM downstream phosphorylated Akt (protein kinase B) and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium remain unclear.

OBJECTIVE:

To explore the effects of low-dose HCQ on the expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium in a rat model.

METHODS:

Myocardial infarction (MI) was induced experimentally in a subset of rats, while others underwent sham operation (sham). Three days after operation, surviving Sprague-Dawley male rats were divided into MI+HCQ, MI, sham+HCQ and sham groups. MI+HCQ and sham + HCQ groups were treated with HCQ (3.4 mg/kg); and MI and sham groups were treated with phosphate buffered (ie, physiological) saline (10 mL/kg) by gavage every day for 12 weeks. The expression of phosphorylated Akt and p53 proteins and cardiomyocyte apoptosis in the peri-infarct myocardium was detected by Western blot and terminal deoxynucleotidyl transferase dUTP nick end labelling, respectively.

RESULTS:

Twelve weeks after treatment, the expression of phosphorylated Akt protein was significantly increased (P<0.05). Expression of phosphorylated p53 protein was not significantly different (P>0.05) in the peri-infarct myocardium of the MI+HCQ group from that in the MI group. The cardiomyocyte apoptosis rate in the peri-infarct myocardium was significantly decreased in the MI+HCQ group compared with the MI group (P<0.05).

CONCLUSION:

Low-dose HCQ can significantly increase the expression of phosphorylated Akt protein without significantly impacting expression of phosphorylated p53 protein in the peri-infarct myocardium. Accordingly, it can inhibit cardiomyocyte apoptosis in the peri-infarct myocardium.     

Reduction in oxidative stress and modulation of heart failure subsequent to myocardial infarction in rats

BACKGROUND:

Patients surviving myocardial infarction (MI) are at a heightened risk for the development of congestive heart failure. This clinical syndrome has been associated with an antioxidant deficit and elevated oxidative stress in the myocardium. Effects of dietary vitamin E, a lipid-soluble antioxidant, on myocardial anti-oxidant enzyme activities, oxidative stress and hemodynamic function, were examined separately in the viable left ventricle (LV) and right ventricle (RV) of rats at 16 weeks post-MI.

METHODS AND RESULTS:

Animals were fed either a basal diet or a diet enriched with 1500 U of vitamin E/kg beginning two weeks before MI-inducing surgery and continued 16 weeks post-MI. In the MI animals on the basal diet, LV systolic pressure (LVSP) and RVSP were significantly depressed and LV end-diastolic pressure (LVEDP) and RVEDP were significantly elevated. These hemodynamic alterations were accompanied by clinical signs of heart failure including dyspnea, lethargy and cyanotic limbs. Supplementation of MI animals with dietary vitamin E resulted in complete normalization of RVSP and RVEDP. An increase in LVSP and a decrease in LVEDP was observed in the vitamin E-supplemented MI animals, although mild residual LV dysfunction remained. The myocardial enzymatic antioxidants catalase and glutathione peroxidase declined substantially in each of the ventricles of unsupplemented MI animals. Myocardial levels of vitamin E were reduced by 33% in the LV and no change was observed in the RV of the MI animals. Vitamin E-supplemented control animals and MI animals showed a significant increase in vitamin E levels in both ventricles. Myocardial oxidative stress, as assessed by lipid peroxidation and the ratio of reduced to oxidized glutathione, was significantly increased in each of the respective ventricles of untreated MI animals. Supplementation with dietary vitamin E resulted in a substantial increase in the myocardial activities of catalase and glutathione peroxidase in both the LV and RV. Furthermore, an increase in the ratio of reduced to oxidized glutathione concomitant with significantly less lipid peroxidation was also observed in each of the respective ventricles of MI animals supplemented with vitamin E. No overt clinical signs of heart failure were evident in these vitamin E-supplemented animals.

CONCLUSIONS:

An improved myocardial redox state and endogenous antioxidant reserve with vitamin E therapy, coupled with the modulation of the development of heart failure, lend strong support in favour of a pathophysiological role for increased oxidative stress in the pathogenesis of heart failure, at least in experimental animals. Association between an increase in oxidative stress and cardiac events in patients requires further examination.     

Utility of 64-MSCT in assessing acute non-reperfused myocardial infarct size

Objective To evaluate the utility of multi-slice computed tomography (MSCT) in assessing acute non-reperfused myocardial infarct size. Methods Seven domestic pigs (mean weight 17.3 ± 1.9 kg) underwent ligation of the distal left anterior descending artery to establish a model of acute myocardial infarction (MI). MSCT and triphenyltetrazolium chloride (TTC) staining were performed two hours later. The following data were acquired and analyzed: MI volume (%), CT values of the infarcted region, left ventricular cavity and normal cardiac tissue at various scanning time-points (1, 5, 10, 15, 20 min after contrast injection). Results Using MSCT, the overall MI volume showed a time-dependent decrease, with a reduction of 28.87% after 20 min. The greatest reduction occurred at the 5 min time-point. In TTC staining, MI volume was 9.87% ± 2.44%. When MI size, as determined by MSCT, was compared with that by TTC staining in Bland-Altman plots, there was a better agreement at 5, 10, and 15 min time-points at 1 and 20 min. Conclusions The study indicates that double-phase scanning examination using MSCT is a useful tool to assess MI size, and the optimal late-phase scanning time-point set within 5–15 min of contrast injection.     

Aerobic Interval Exercise Training Induces Greater Reduction in Cardiac Workload in the Recovery Period in Rats

Background

Aerobic interval exercise training has greater benefits on cardiovascular function as compared with aerobic continuous exercise training.

Objective

The present study aimed at analyzing the effects of both exercise modalities on acute and subacute hemodynamic responses of healthy rats.

Methods

Thirty male rats were randomly assigned into three groups as follows: continuous exercise (CE, n = 10); interval exercise (IE, n = 10); and control (C, n = 10). Both IE and CE groups performed a 30-minute exercise session. The IE group session consisted of three successive 4-minute periods at 60% of maximal velocity (Max Vel), with 4-minute recovery intervals at 40% of Max Vel. The CE group ran continuously at 50% of Max Vel. Heart rate (HR), blood pressure(BP), and rate pressure product (RPP) were measured before, during and after the exercise session.

Results

The CE and IE groups showed an increase in systolic BP and RPP during exercise as compared with the baseline values. After the end of exercise, the CE group showed a lower response of systolic BP and RPP as compared with the baseline values, while the IE group showed lower systolic BP and mean BP values. However, only the IE group had a lower response of HR and RPP during recovery.

Conclusion

In healthy rats, one interval exercise session, as compared with continuous exercise, induced similar hemodynamic responses during exercise. However, during recovery, the interval exercise caused greater reductions in cardiac workload than the continuous exercise.     

Obesity Preserves Myocardial Function During Blockade of the Glycolytic Pathway

Background

Obesity is defined by excessive accumulation of body fat relative to lean tissue. Studies during the last few years indicate that cardiac function in obese animals may be preserved, increased or diminished.

Objective

Study the energy balance of the myocardium with the hypothesis that the increase in fatty acid oxidation and reduced glucose leads to cardiac dysfunction in obesity.

Methods

30-day-old male Wistar rats were fed standard and hypercaloric diet for 30 weeks. Cardiac function and morphology were assessed. In this paper was viewed the general characteristics and comorbities associated to obesity. The structure cardiac was determined by weights of the heart and left ventricle (LV). Myocardial function was evaluated by studying isolated papillary muscles from the LV, under the baseline condition and after inotropic and lusitropic maneuvers: myocardial stiffness; postrest contraction; increase in extracellular Ca2+ concentration; change in heart rate and inhibitor of glycolytic pathway.

Results

Compared with control group, the obese rats had increased body fat and co-morbities associated with obesity. Functional assessment after blocking iodoacetate shows no difference in the linear regression of DT, however, the RT showed a statistically significant difference in behavior between the control and the obese group, most notable being the slope in group C.

Conclusion

The energy imbalance on obesity did not cause cardiac dysfunction. On the contrary, the prioritization of fatty acids utilization provides protection to cardiac muscle during the inhibition of glycolysis, suggesting that this pathway is fewer used by obese cardiac muscle.     

Cardioprotective effects of Guanxinshutong (GXST) against myocardial ischemia/ reperfusion injury in rats

Background The protective effects against reperfusion injury of cardioprotective drugs have recently been evaluated and found to be inadequate. Guanxinshutong (GXST), a combination of the traditional herb and Mongolian medicine, is effective and safe in treating angina pectoris in clinical trials. We assess the cardioprotective effects of GXST against myocardial ischemia and reperfusion (MI/R) injury in rats and explore its possible mechanism. Methods Forty-five male Sprague Dawley rats were randomized into three groups: non-MI/R group (Sham, n = 15), MI/R group treated with vehicle (Control, n = 15) and MI/R group treated with GXST (Drug, n = 15). MI/R was induced by ligation of the left anterior descending coronary artery (LAD) for 30 minutes, followed by 2/24 hour reperfusion in the Control and Drug groups. In the Sham group, the LAD was exposed without occlusion. GXST powder (in the Drug group) or saline (in the Control and Sham groups) were administered via direct gastric gavage from 7 day prior to surgery. Blood samples were collected from the carotid artery (10 rats each group) after 2 hours of reperfusion, to determine the levels of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) using enzyme-linked immunosorbent assays. The animals were then sacrificed and the hearts were harvested for histopathology and western blot analysis. Infarct size was measured in the remaining five rats in each group after 24 hours reperfusion. Results GXST significantly decreased levels of TNF-α, IL-1β, IL-6, ICAM-1, apoptosis index (AI) and infarct size. GXST also obviously inhibited nuclear factor kappa B (NF-κB) activity when compared with the Control group (all P < 0.05). Conclusions GXST is effective in protecting the myocardium against MI/R injury in rats. Its possible cardioprotective mechanism involves inhibition of the inflammatory response and apoptosis following MI/R injury.     

Obesity Resistance Promotes Mild Contractile Dysfunction Associated with Intracellular Ca2+ Handling

Background

Diet-induced obesity is frequently used to demonstrate cardiac dysfunction. However, some rats, like humans, are susceptible to developing an obesity phenotype, whereas others are resistant to that.

Objective

To evaluate the association between obesity resistance and cardiac function, and the impact of obesity resistance on calcium handling.

Methods

Thirty-day-old male Wistar rats were distributed into two groups, each with 54 animals: control (C; standard diet) and obese (four palatable high-fat diets) for 15 weeks. After the experimental protocol, rats consuming the high-fat diets were classified according to the adiposity index and subdivided into obesity-prone (OP) and obesity-resistant (OR). Nutritional profile, comorbidities, and cardiac remodeling were evaluated. Cardiac function was assessed by papillary muscle evaluation at baseline and after inotropic maneuvers.

Results

The high-fat diets promoted increase in body fat and adiposity index in OP rats compared with C and OR rats. Glucose, lipid, and blood pressure profiles remained unchanged in OR rats. In addition, the total heart weight and the weight of the left and right ventricles in OR rats were lower than those in OP rats, but similar to those in C rats. Baseline cardiac muscle data were similar in all rats, but myocardial responsiveness to a post-rest contraction stimulus was compromised in OP and OR rats compared with C rats.

Conclusion

Obesity resistance promoted specific changes in the contraction phase without changes in the relaxation phase. This mild abnormality may be related to intracellular Ca2+ handling.     

Effects of therapy using the Celacade system on structural and functional cardiac remodelling in rats following myocardial infarction

BACKGROUND:

Immune modulation by the Celacade system (Vasogen Inc, Canada) decreases mortality and hospitalization in human heart failure.

OBJECTIVES:

To study the effects of Celacade in rats on acute cytokine expression after coronary artery ligation, cardiac dimensions following myocardial infarction (MI), and systolic and diastolic function of cardiac muscle in MI.

METHODS:

Celacade treatment was administered 14 days before coronary artery ligation and monthly after the surgery. Cytokine expression in cardiac tissue was measured on days 1 and 7 by ELISA in sham rats and in rats with MI (with or without Celacade treatment). Echocardiograms were obtained serially for 16 weeks. Force and sarcomere length (SL) were measured by strain gauge and laser diffraction in isolated right ventricle trabeculas at 16 weeks. The inotropic effect of pacing on force was quantified as F_{5 Hz/0.5 Hz}. Diastolic dysfunction was quantified as the root mean square of spontaneous SL fluctuations.

RESULTS:

Celacade inhibited transforming growth factor beta-1 production in the infarct area on day 7 (191.6±22.6 pg/mg versus 275.4±30.1 pg/mg; P<0.05), but did not attenuate cardiac dilation in MI. Celacade restored positive inotropism of pacing in MI (F_{5 Hz/0.5 Hz} in Celacade, 219.1±46.7%; MI, 148.1±27.1% [P<0.05 compared with 211.4±37.9% in sham]). Celacade reduced diastolic dysfunction in MI (root mean square of spontaneous SL fluctuations: 121±15% and 143±19% with Celacade versus 184±19% and 190±26% without Celacade at 26°C and 36°C, respectively) compared with sham (100%; P<0.05).

CONCLUSIONS:

Celacade reduces the increase of transforming growth factor beta-1 expression during the acute stage of MI in rats, but does not prevent chronic cardiac dilation. Celacade restores the positive inotropic effect of increased pacing rate in trabeculas from rat right ventricles with large MIs and reduces diastolic dysfunction.     

The antiapoptotic effect of mesenchymal stem cell transplantation on ischemic myocardium is enhanced by anoxic preconditioning

BACKGROUND:

Cardiomyocyte apoptosis takes place at an early stage after myocardial infarction (MI). Therapy with mesenchymal stem cells (MSCs) is reported to reduce apoptosis.

OBJECTIVES:

To determine whether anoxic preconditioning (AP) could enhance the antiapoptotic effect of MSCs.

METHODS:

Cultured cardiomyocytes were treated with Dulbecco’s modified Eagle’s medium (as a control), MSCs or AP-MSCs, and were exposed to hypoxia/reoxygenation. Apoptotic cardiomyocytes were stained with Annexin V fluorescein isothiocyanate (BioVision, USA), visualized by fluorescence microscopy and analyzed by flow cytometry. In vivo, MI was produced in Sprague-Dawley rats by permanent ligation of the left anterior descending coronary artery and the left ventricles were randomly injected with Dulbecco’s modified Eagle’s medium, MSCs or AP-MSCs one week after MI. The cardiomyocyte apoptotic rate in peri-infarcted areas was assessed by terminal deoxynucleotidyltransferase-mediated 2′-deoxyuridine 5′-triphosphate nick end labelling assay one week after transplantation. Cardiac function was assessed by echocardiography four weeks after transplantation. Infarct size was measured by hematoxylin and eosin staining one and four weeks after transplantation. The expression of Bcl-2, Bax protein and cleaved cysteine-aspartic acid protease-3 was analyzed by Western blot techniques.

RESULTS:

Cardiomyocyte apoptosis (both induced by hypoxia/reoxygenation and MI) was significantly reduced by treating with MSCs and AP-MSCs, the Bcl-2 to Bax protein ratio was increased and cleaved cysteine-aspartic acid protease-3 was decreased. AP-MSCs were superior to MSCs.

CONCLUSIONS:

MSCs protected the infarcted heart by preventing cardiomyocyte apoptosis and AP enhanced the cardioprotective effects of MSCs.     

Gender differences in the etiology of heart failure: A systematic review

Background

Heart failure (HF) is an increasing problem for the aging population, specifically among women. The etiology of HF influences both the selection and outcome of the treatment. There are variations between genders in morbidity and mortality in different studies, possibly reflecting etiology. The objective of this study was to examine the strength of evidence available for gender differences in the etiology of chronic heart failure.

Methods

Computer-assisted searches from 1980–2009 for gender differences in the etiology of heart failure were performed (Medline, EMBASE and PubMed). From 2347 abstracts reviewed based on inclusion criteria, 35 original articles were chosen for review. Data extraction was based on observational studies (prospective/retrospective cohort or cross sectional) with a mean follow up of 3 months. There was no interrater variability between the 2 reviewers on data-extraction.

Results

Ventricular systolic dysfunction being more associated with male sex, but female sex was more reported to be associated with preserved left ventricular function. Ischemic etiology and associated coronary heart disease were strongly correlated with male sex. The risk for HF was dramatically more elevated for women with systolic hypertension but the association for diabetes mellitus as the etiology of HF was somewhat equal between males and females.

Conclusions

One of the limitations in reaching conclusions about gender differences in cardiovascular disease is that many major clinical trials do not include a gender analysis nor they are powered to do so as women are under-represented in most of the HF studies. The need remains for a well designed prospective study of sufficient numbers of male and female patients with and without heart failure and analyzing etiology and risk factors based on the sex differences.     

Intermittent claudication: From its risk factors to its long-term prognosis in men. The Quebec Cardiovascular Study

BACKGROUND:

The natural history of intermittent claudication, from its risk factors to its cardiovascular prognosis, has been reported in few prospective studies.

OBJECTIVE:

To assess incident intermittent claudication, as well as its risk factors and long-term prognosis in men.

METHODS:

A random sample of 4376 men 35 to 64 years of age from Quebec City (Quebec), who were free of cardiovascular disease (CVD), was evaluated in 1974 for CVD risk factors and followed until 1998. To assess the prognosis, the event rates between 1985 and 1998 were computed among men with incident claudication without other CVD, incident survivors of a first myocardial infarction (MI) without other CVD and men free of CVD between 1974 and 1985.

RESULTS:

From 1974 to 1998, 300 men developed intermittent claudication. Tobacco consumption, high systolic blood pressure and diabetes at least doubled the adjusted RR (aRR) of intermittent claudication. In 1985, there were 80 claudicants, 2868 men free of CVD and 68 survivors of a first MI. During the 13-year follow-up, a new CVD occurred in 48.8% of the claudicants, in 18.9% of men without CVD (aRR 2.08; 95% CI 1.48 to 2.90) and in 45.6% of MI survivors (aRR compared with claudicants 1.12; 95% CI 0.69 to 1.79). There was also no significant difference between claudicants and MI survivors for fatal CVD, nonfatal CVD and total mortality.

CONCLUSIONS:

Men with intermittent claudication are at high risk for CVD that may be equivalent to men with previous MI.     

Sympathetic nerve traffic and asymmetric dimethylarginine in chronic kidney disease

Summary

Background and objectives

Sympathetic overactivity and high levels of the endogenous inhibitor of NO synthase asymmetric dimethylarginine (ADMA) are prevalent risk factors in chronic kidney disease (CKD).

Design, setting, participants, & measurements

In 48 stage 2 to 4 CKD patients, we investigated the relationship between efferent postganglionic muscle sympathetic nerve traffic (microneurography) and circulating ADMA and analyzed the links between these risk factors and estimated GFR (eGFR), proteinuria, and different parameters of left ventricular (LV) geometry.

Results

CKD patients characterized by sympathetic nerve traffic values in the third tertile showed the highest ADMA levels, and this association was paralleled by a continuous, positive relationship between these two risk factors (r = 0.32, P = 0.03) independent of other confounders. Both sympathetic nerve traffic and ADMA were inversely related to eGFR and directly to proteinuria and LV geometry. Remarkably, the variance of eGFR, proteinuria, and LV geometry explained by sympathetic nerve traffic and ADMA largely overlapped because sympathetic nerve traffic but not ADMA was retained as a significant correlate of the eGFR (P < 0.001) and of the relative wall thickness or the left ventricular mass index/LV volume ratio (P = 0.05) in models including both risk factors. ADMA, but not sympathetic nerve traffic, emerged as an independent correlate of proteinuria (P = 0.003) in a model including the same covariates.

Conclusions

Sympathetic activity and ADMA may share a pathway leading to renal disease progression, proteinuria, and LV concentric remodeling in CKD patients.     

Effects of intermittent and long-term glucose-insulin-potassium infusion in patients with systolic heart failure

BACKGROUND

Although single dose and short-term glucose-insulin-potassium (GIK) infusions are known to have positive cardiac effects, the effects of repeated and long-term GIK infusion on left ventricular (LV) systolic function and brain natriuretic peptide (BNP) levels are unknown.

OBJECTIVE

To investigate the effects of repeated and long-term GIK infusion on LV systolic function and BNP levels.

METHODS

Thirty-three patients diagnosed with ischemic cardiomyopathy were included in the study. Patients were divided into two groups: the GIK group (n=19) and the control group (n=14). GIK solutions (1000 mL 20% dextrose, 60 U insulin and 50 mmol/L KCl) were administered at 1 mL/kg/h for 24 h on the first, third and fifth days. The patients were examined by echocardiography at 24 h, one week and one month after the start of treatment. BNP levels were measured before and after GIK infusion.

RESULTS

In the GIK group, baseline ejection fraction (EF) was 29.2±10.3%. After one week, EF elevated to 40.8±10.8% (P=0.001). The EF after one month (37.1±10.9%) was less than the EF in the first week, but it was significantly higher than baseline in the GIK group (P=0.01). However, no significant changes in EF were observed after one week and one month in the control group (P=0.1 and P=0.2, respectively). BNP levels after GIK infusion was significantly lower than baseline level in the GIK group (P=0.01).

CONCLUSION

Intermittent and long-term GIK infusion has beneficial effects on LV systolic function in a short and intermediate amount of time. Decrease in BNP levels may indicate effective GIK treatment. Intermittent and long-term GIK infusion could be a promising treatment option in patients with systolic heart failure.     

Circulating miR-133a and miR-423-5p fail as biomarkers for left ventricular remodeling after myocardial infarction

Background

Recent studies have suggested that the microRNAs miR-133a and miR-423-5p may serve as useful biomarkers in patients with left ventricular (LV) heart failure or with LV remodeling after myocardial infarction (MI). These results were however obtained in small series of patients and control subjects were used as reference groups. Whether these microRNAs may be indicators of the degree of LV remodeling after MI is unknown.

Methods

246 patients with a first anterior Q-wave MI were included. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI and analyzed at a core laboratory. We investigated the temporal profile (baseline, 1, 3 and 12 months) of circulating miR-133a and miR-423-5p and their relations with cardiac biomarkers (B-type natriuretic peptide, C-reactive protein, and cardiac troponin I) and LV remodeling during the 1 year follow-up.

Results

There were time-dependent changes in the levels of circulating miR-133a and miR-423-5p with significant increase of miR-133a at 12 months compared to 3 months and significant increase of miR-423-5p at 1, 3, and 12 months compared to baseline. However, miR-133a and miR-423-5p were not associated with indices of LV function and LV remodeling serially assessed during a 1 year period after an acute anterior MI, nor with B-type natriuretic peptide.

Conclusions

Circulating levels of miR-133a and miR-423-5p are not useful biomarkers of LV remodeling after MI.     

Infarct Size as Predictor of Systolic Functional Recovery after Myocardial Infarction

Background

The effects of modern therapy on functional recovery after acute myocardial infarction (AMI) are unknown.

Objectives

To evaluate the predictors of systolic functional recovery after anterior wall AMI in patients undergoing modern therapy (reperfusion, aggressive platelet antiaggregant therapy, angiotensin-converting enzyme inhibitors and beta-blockers).

Methods

A total of 94 consecutive patients with AMI with ST-segment elevation were enrolled. Echocardiograms were performed during the in-hospital phase and after 6 months. Systolic dysfunction was defined as ejection fraction value < 50%.

Results

In the initial echocardiogram, 64% of patients had systolic dysfunction. Patients with ventricular dysfunction had greater infarct size, assessed by the measurement of total and isoenzyme MB creatine kinase enzymes, than patients without dysfunction. Additionally, 24.5% of patients that initially had systolic dysfunction showed recovery within 6 months after AMI. Patients who recovered ventricular function had smaller infarct sizes, but larger values of ejection fraction and E-wave deceleration time than patients without recovery. At the multivariate analysis, it can be observed that infarct size was the only independent predictor of functional recovery after 6 months of AMI when adjusted for age, gender, ejection fraction and E-wave deceleration time.

Conclusion

In spite of aggressive treatment, systolic ventricular dysfunction remains a frequent event after the anterior wall myocardial infarction. Additionally, 25% of patients show functional recovery. Finally, infarct size was the only significant predictor of functional recovery after six months of acute myocardial infarction.     

Relationship Between Left Atrial Volume and Diastolic Dysfunction in 500 Brazilian Patients

Background

Left atrial volume index (LAVI) increase has been associated to left ventricle (LV) diastolic dysfunction (DD), a marker of cardiovascular events (atrial fibrillation, stroke, heart failure, death).

Objective

To evaluate the relationship between LAVI and diferente grades od DD in Brazilian patients submitted to echocardiogram, studying LAVI increase determinants in this sample.

Methods

We have selected 500 outpatients submitted to echocardiography, after excluding arrhythmia, valvar or congenital cardiopathy, permanent pacemaker or inadequate ecocardiographic window. LAVI was obtained according to Simpson''s method. DD was classified according to current guidelines. The clinical and echocardiographic variables were submitted to linear regression multivariate analysis.

Results

Mean age was 52 ± 15 years old, 53% were male, 55% had arterial hypertension, 9% had coronary artery disease, 8% were diabetic, 24% were obese, 47% had LV hypertrophy. The mean ejection fraction of the left ventricle was 69.6 ± 7,2%. The prevalence of DD in this sample was 33.8% (grade I: 66%, grade II: 29% e grade III: 5%). LAVI increased progressively according to DD grade: 21 ± 4 mL/m² (absent), 26 ± 7 mL/m² (grade I), 33 ± 5 mL/m² (grade II), 50 ± 5 mL/m2 (grade III) (p < 0,001). In this sample, LAVI increase independent predictors were age, left ventricular mass, relative wall thickness, LV ejection fraction and E/e'' ratio.

Conclusion

DD contributes to left atrial remodeling. LAVI increases as an expression of DD severity and is independently associated to age, left ventricle hypertrophy, systolic dysfunction and increased LV filling pressures.