Improvement of Left Ventricular Remodelling by Inhibition of NF-κB in a Rat Model of Myocardial Infarction.

BACKGROUND: To investigate the effects of inhibition of NF-κB activation on left ventricular (LV) remodelling in a rat model of myocardial infarction (MI). METHODS: The acute MI model was established by ligation of left anterior descending coronary artery. Pyrrolidine dithiocarbamate (PDTC) (20mg/kg, Qd) was administered intraperitoneally to inhibit NF-κB activation. Eight weeks later, the cardiac structure and LV ejection fraction were assessed with echocardiography. The rat body, heart, and LV weights were measured to calculate LV mass indices. Activation of NF-κB in non-infarcted myocardium was detected by a TransAM NF-κB p65 Transcription Factor Assay Kit. Cardiac collagen volume fraction was evaluated by Masson staining. RESULTS: Eight weeks after the MI model was established, the LV posterior wall thickness in PDTC and MI group was 1.75±0.07mm and 1.85±0.07mm respectively (p<0.05). The LV mass index in the PDTC group (2.53±0.09) was lower than in the MI group (2.65±0.08, p<0.05). The LVEF in the PDTC group (63.89%±4.21%) was higher than in the MI group (42.73%±8.94%, p<0.05). The interstitial collagen deposition in the non-infarcted myocardium in the PDTC group was less than in the MI group (7.25%±1.88% vs. 10.09%±2.19%, p<0.05). CONCLUSION: Inhibition of activation of NF-κB may result in improvement of myocardial remodelling after myocardial infarction, which is possibly attributable to reduced collagen deposition in non-infarcted areas.

Left ventricular remodelling in bicuspid aortic valve disease.

AIMS: Characterization of left ventricular (LV) geometric pattern and LV mass could provide an important insight into the pathophysiological adaptations of the LV to pressure and/or volume overload in patients with bicuspid aortic valve (BAV) and significant (≥moderate) aortic valve (AV) disease. This study aimed to characterize LV remodelling and its prognostic impact in patients with BAV according to the predominant type of valvular dysfunction. METHODS AND RESULTS: In this international, multicentre BAV registry, 1345 patients [51.0 (37.0-63.0) years, 71% male] with significant AV disease were identified. Patients were classified as having isolated aortic stenosis (AS) (n = 669), isolated aortic regurgitation (AR) (n = 499) or mixed aortic valve disease (MAVD) (n = 177). LV hypertrophy was defined as a LV mass index >115 g/m2 in males and >95 g/m2 in females. LV geometric pattern was classified as (i) normal geometry: no LV hypertrophy, relative wall thickness (RWT) ≤0.42, (ii) concentric remodelling: no LV hypertrophy, RWT >0.42, (iii) concentric hypertrophy: LV hypertrophy, RWT >0.42, and (iv) eccentric hypertrophy: LV hypertrophy, RWT ≤0.42. Patients were followed-up for the endpoints of event-free survival (defined as a composite of AV repair/replacement and all-cause mortality) and all-cause mortality. Type of AV dysfunction was related to significant variations in LV remodelling. Higher LV mass index, i.e. LV hypertrophy, was independently associated with the composite endpoint for patients with isolated AS [hazard ratio (HR) 1.08 per 25 g/m2, 95% confidence interval (CI) 1.00-1.17, P = 0.046] and AR (HR 1.19 per 25 g/m2, 95% CI 1.11-1.29, P < 0.001), but not for those with MAVD. The presence of concentric remodelling, concentric hypertrophy and eccentric hypertrophy were independently related to the composite endpoint in patients with isolated AS (HR 1.54, 95% CI 1.06-2.23, P = 0.024; HR 1.68, 95% CI 1.17-2.42, P = 0.005; HR 1.59, 95% CI 1.03-2.45, P = 0.038, respectively), while concentric hypertrophy and eccentric hypertrophy were independently associated with the combined endpoint for those with isolated AR (HR 2.49, 95% CI 1.35-4.60, P = 0.004 and HR 3.05, 95% CI 1.71-5.45, P < 0.001, respectively). There was no independent association observed between LV remodelling and the combined endpoint for patients with MAVD. CONCLUSIONS: LV hypertrophy or remodelling were independently associated with the composite endpoint of AV repair/replacement and all-cause mortality for patients with isolated AS and isolated AR, although not for patients with MAVD.

Spotlights on some electrocardiographic paradigms: How should we evaluate normal reference values of Tp-Te interval, Tp-Te dispersion and Tp-Te/QT ratio?

BACKGROUND: Experimental and clinical studies evaluating the Tp-Te interval and Tp-Te/QT ratio have reported conflicting data. The overlap between normal Tp-Te/QT ratios (0.17 ±0.02-0.27 ±0.06 ms) and pathological values (0.20 ±0.03-0.30 ±0.06 ms) measured in earlier studies has raised questions about this ECG measurement technique. OBJECTIVES: To analyze normal values of the Tp-Te interval, Tp-Te dispersion Tp-Te(d) and the Tp-Te/QT ratio based on electrocardiographic (ECG) assessment across sex and age groups in a healthy Turkish population. MATERIAL AND METHODS: A total of 1,485 healthy participants (723 men) were enrolled into the study. The age of the participants ranged 17-75 years and they did not have either any cardiovascular/systemic disorders or risk factors for atherosclerosis which were detected with physical examination and laboratory tests. The Tp-Te interval, Tp-Te(d) and Tp-Te/QT ratio were determined from V1-V6 derivations. RESULTS: For the entire study, the median Tp-Te interval was 66.0 (64.0-70.0) ms, the Tp-Te(d) was 15.0 (10.0-20.0) ms, and the Tp-Te/QT ratio was 0.18 (0.17-0.19). The Pearson's correlation test demonstrated that the Tp-Te/QT ratio significantly correlated with older age (r = 0.297; p < 0.0001), left ventricular (LV) end-diastolic diameter (LVEDD; r = 0.481; p < 0.0001), body mass index (BMI; r = 0.421; p < 0.0001), body surface area (BSA; r = 0.191; p < 0.0001), LV end-diastolic volume (LVEDV; r = 0.484; p < 0.0001), LVEDV index (r = 0.450; p < 0.0001), LV mass (r = 0.548; p < 0.0001), and LV mass index (r = 0.539; p < 0.0001). CONCLUSIONS: The reference values for Tp-Te interval, Tp-Te(d) and Tp-Te/QT ratio are associated with age, BMI, BSA, LVEDV, LVEDV index, LV mass, and LV mass index. These structural elements should be considered when using these ECG parameters for assessing repolarization inhomogeneity. These findings may guide further studies assessing healthy and diseased populations.

Physical Activity Is Associated With Reduced Left Ventricular Mass in Obese and Hypertensive African Americans.

BACKGROUND: Physical activity (PA) has been associated with decreased left ventricular (LV) hypertrophy in previous studies. However, little is known about the relationship between PA and LV structure and factors which influence this relationship among African Americans. METHODS: We evaluated 1,300 African Americans with preserved LV ejection fraction (EF > 50%) from the Genetic Epidemiology Network of Arteriopathy (GENOA) Study (mean age 62.4 years, 73% women). PA index was calculated as 3 * heavy activity hours + 2 * moderate activity hours + slight activity hours/day. The relationship between PA index and LV structure was evaluated using generalized estimating equation. The association between PA index and LV mass index by age group, sex, body mass index (BMI), history of hypertension, diabetes or coronary heart disease, estimated glomerular filtration rate, and current smoking status were plotted. RESULTS: After adjustment for these factors, higher PA index was independently associated with lower LV mass index (P < 0.05). There were significant interactions between PA index and obesity (BMI ≥ 30) and history of hypertension on LV mass index (P for interaction <0.05, for both). Higher PA index was associated with lower LV mass index more in obese or hypertensive participants compared with nonobese or nonhypertensive participants. CONCLUSIONS: Higher PA index was associated with reduced LV hypertrophy in obese and hypertensive African Americans. Prospective studies aimed at assessing whether increasing PA prevents LV hypertrophy and potentially reduces the risk of heart failure in these at risk groups are warranted.

Ventricular hypertrophy and left atrial dilatation persist and are associated with reduced survival after valve replacement for aortic stenosis.

OBJECTIVES: We sought to understand the factors modulating left heart reverse remodeling after aortic valve replacement, the relationship between the preoperative symptoms and modulators of left heart remodeling, and their influence on long-term survival. METHODS: From October 1991 to January 2008, 4264 patients underwent primary aortic valve replacement for aortic stenosis. Changes in the time course of left ventricular reverse remodeling were assessed using 5740 postoperative transthoracic echocardiograms from 3841 patients. RESULTS: Left ventricular hypertrophy rapidly declined after surgery, from 137 ± 42 g/m(2) preoperatively to 115 ± 27 by 2 years and remained relatively constant but greater than the upper limit of normal. The most important risk factor for residual left ventricular hypertrophy was greater preoperative left ventricular hypertrophy (P < .0001). Other factors included a greater left atrial diameter (reflecting diastolic dysfunction), a lower ejection fraction, and male gender. An increased postoperative transprosthesis gradient was associated with greater residual left ventricular hypertrophy; however, its effect was minimal. Preoperative severe left ventricular hypertrophy and left atrial dilatation reduced long-term survival, independent of symptom status. CONCLUSIONS: Severe left ventricular hypertrophy with left atrial dilatation can develop from severe aortic stenosis, even without symptoms. These changes can persist, are associated with decreased long-term survival even after successful aortic valve replacement, and could be indications for early aortic valve replacement if supported by findings from an appropriate prospective study.

Functional iron deficiency and diastolic function in heart failure with preserved ejection fraction.

BACKGROUND: Functional iron deficiency (FID) is an independent risk factor for poor outcome in advanced heart failure with reduced EF, but its role in heart failure with preserved EF (HFPEF) remains unclear. We aimed to investigate the impact of FID on cardiac performance determined by pressure-volume loop analysis in HFPEF. METHODS: 26 HFPEF patients who showed an increase in LV stiffness by pressure-volume (PV) loop analysis obtained by conductance-catheterization, performed exercise testing, echocardiographic examination including tissue Doppler and determination of iron metabolism: serum iron, ferritin and transferrin saturation. HFPEF patients who provided ferritin <100 µg/l or ferritin of 100-299 µg/l in combination with transferrin saturation <20% were defined as having FID. In 14 patients the expression of transferrin receptor was determined from available endomyocardial biopsies. RESULTS: Fifteen out of 26 HFPEF patients showed FID without anemia. Compared to control subjects and HFPEF patients without FID, HFPEF patients with FID showed an up-regulation of the myocardial transferrin receptor expression (p<0.05). No differences between HFPEF patients with and without iron deficiency were found in heart dimensions, systolic and diastolic function obtained by PV-loop and echocardiography analysis. According to the linear regression analysis, LV stiffness was correlated with peak oxygen uptake (r=-0.636, p<0.001) but not with the ferritin level or transferrin saturation. No relation was found between FID and exercise capacity. The association of LV stiffness with exercise performance was independent from the level of iron deficiency. CONCLUSION: In non-anemic HFPEF patients, cardiac dysfunction and impaired exercise capacity occur independently of FID.