Increased cardiac angiotensin II levels induce right and left ventricular hypertrophy in normotensive mice.

Angiotensin II is a potent arterial vasoconstrictor and induces hypertension. Angiotensin II also exerts a trophic effect on cardiomyocytes in vitro. The goals of the present study were to document an in vivo increase in cardiac angiotensins in the absence of elevated plasma levels or hypertension and to investigate prevention or regression of ventricular hypertrophy by renin-angiotensin system blockade. We demonstrate that high cardiac angiotensin II is directly responsible for right and left ventricular hypertrophy. We used transgenic mice overexpressing angiotensinogen in cardiomyocytes characterized by cardiac hypertrophy without fibrosis and normal blood pressure. Angiotensin-converting enzyme inhibition and angiotensin II type 1 receptor blockade prevent or normalize ventricular hypertrophy. Surprisingly, in control mice, receptor blockade decreases tissue angiotensin II despite increased plasma levels. This suggests that angiotensin II may be protected from metabolization by binding to its receptor. Blocking of the angiotensin II type 1 receptor rather than enhanced stimulation of the angiotensin II type 2 receptor may prevent remodeling and account for the beneficial effects of angiotensin antagonists.

Performance of classic electrocardiographic criteria for left ventricular hypertrophy in an African population.

ECG criteria for left ventricular hypertrophy (LVH) have been almost exclusively elaborated and calibrated in white populations. Because several interethnic differences in ECG characteristics have been found, the applicability of these criteria to African individuals remains to be demonstrated. We therefore investigated the performance of classic ECG criteria for LVH detection in an African population. Digitized 12-lead ECG tracings were obtained from 334 African individuals randomly selected from the general population of the Republic of Seychelles (Indian Ocean). Left ventricular mass was calculated with M-mode echocardiography and indexed to body height. LVH was defined by taking the 95th percentile of body height-indexed LVM values in a reference subgroup. In the entire study sample, 16 men and 15 women (prevalence 9.3%) were finally declared to have LVH, of whom 9 were of the reference subgroup. Sensitivity, specificity, accuracy, and positive and negative predictive values for LVH were calculated for 9 classic ECG criteria, and receiver operating characteristic curves were computed. We also generated a new composite time-voltage criterion with stepwise multiple linear regression: weighted time-voltage criterion=(0.2366R(aVL)+0.0551R(V5)+0.0785S(V3)+ 0.2993T(V1))xQRS duration. The Sokolow-Lyon criterion reached the highest sensitivity (61%) and the R(aVL) voltage criterion reached the highest specificity (97%) when evaluated at their traditional partition value. However, at a fixed specificity of 95%, the sensitivity of these 10 criteria ranged from 16% to 32%. Best accuracy was obtained with the R(aVL) voltage criterion and the new composite time-voltage criterion (89% for both). Positive and negative predictive values varied considerably depending on the concomitant presence of 3 clinical risk factors for LVH (hypertension, age >/=50 years, overweight). Median positive and negative predictive values of the 10 ECG criteria were 15% and 95%, respectively, for subjects with none or 1 of these risk factors compared with 63% and 76% for subjects with all of them. In conclusion, the performance of classic ECG criteria for LVH detection was largely disparate and appeared to be lower in this population of East African origin than in white subjects. A newly generated composite time-voltage criterion might provide improved performance. The predictive value of ECG criteria for LVH was considerably enhanced with the integration of information on concomitant clinical risk factors for LVH.

Physiopathologie de l'hypertrophie ventriculaire gauche. [Physiopathology of left ventricular hypertrophy]

Left ventricular hypertrophy (LVH) is an early complication of hypertension. To a certain degree, this process counteracts the parietal stress induced by high blood pressure. Genetic factors, obesity, high salt diet and different growth factors, notably angiotensin II and noradrenaline, can also predispose to hypertrophic cardiomyopathy. Left ventricular mass is increased on echocardiography in about 20% of hypertensive subjects. LVH is initially associated with a change in myocardial diastolic function and later with abnormal systolic function. It is a major risk factor, a cause of cardiac failure, reduction in coronary reserve and of ventricular arrhythmias. Treatment of hypertension is associated with regression of LVH and preservation or improvement in myocardial diastolic and systolic functions. The decrease in left ventricular mass could reduce the incidence of cardiovascular complications in hypertension.

Independent relations of left ventricular structure with the 24-hour urinary excretion of sodium and aldosterone.

Previous studies reported on the association of left ventricular mass index (LVMI) with urinary sodium or with circulating or urinary aldosterone. We investigated the independent associations of LVMI with the urinary excretion of both sodium and aldosterone. We randomly recruited 317 untreated subjects from a white population (45.1% women; mean age 48.2 years). Measurements included echocardiographic left ventricular (LV) properties, the 24-hour urinary excretion of sodium and aldosterone, plasma renin activity (PRA), and proximal (RNa(prox)) and distal (RNa(dist)) renal sodium reabsorption, assessed from the endogenous lithium clearance. In multivariable-adjusted models, we expressed changes in LVMI per 1-SD increase in the explanatory variables, while accounting for sex, age, systolic blood pressure, and the waist-to-hip ratio. LVMI increased independently with the urinary excretion of both sodium (+2.48 g/m(2); P=0.005) and aldosterone (+2.63 g/m(2); P=0.004). Higher sodium excretion was associated with increased mean wall thickness (MWT: +0.126 mm, P=0.054), but with no change in LV end-diastolic diameter (LVID: +0.12 mm, P=0.64). In contrast, higher aldosterone excretion was associated with higher LVID (+0.54 mm; P=0.017), but with no change in MWT (+0.070 mm; P=0.28). Higher RNa(dist) was associated with lower relative wall thickness (-0.81x10(-2), P=0.017), because of opposite trends in LVID (+0.33 mm; P=0.13) and MWT (-0.130 mm; P=0.040). LVMI was not associated with PRA or RNa(prox.) In conclusion, LVMI independently increased with both urinary sodium and aldosterone excretion. Increased MWT explained the association of LVMI with urinary sodium and increased LVID the association of LVMI with urinary aldosterone.

Heritability of left ventricular structure and function in Caucasian families.

AIMS: The aim of this study was to investigate the heritability as well as genetic and environmental correlations of left ventricular (LV) structural and functional traits in complex pedigrees of a Caucasian population. METHODS AND RESULTS: We randomly recruited 459 white European subjects from 52 families (50% women; mean age 45 years). LV structure was measured by M-mode and 2D echocardiography and LV function was measured by conventional Doppler and tissue Doppler imaging (TDI). Other measurements included blood pressure, anthropometric, and biochemical measurements. We estimated the heritability of LV traits while adjusting for covariables, including sex, age, body height and weight, systolic and diastolic blood pressures, and heart rate. With full adjustment, heritability of LV mass was 0.23 (P= 0.025). The TDI-derived mitral annular velocities Ea and Aa showed moderate heritability (h(2)= 0.36 and 0.53, respectively), whereas the mitral inflow A peak had weak heritability (h(2) = 0.25) and the E peak was not heritable (h(2) = 0.11). We partitioned the total phenotypic correlation when it reached significance, into a genetic and an environmental component. The genetic correlations were 0.61 between the E and Ea peaks and 0.90 between the A and Aa peaks. CONCLUSION: Our study demonstrated moderate heritability for LV mass as well as the mitral annular Ea and Aa peaks. We also found significant genetic correlations between the E and Ea peaks and between the A and Aa peaks. Our current findings support the ongoing research to map and detect genetic variants that contribute to the variation in LV mass and other LV structural and functional phenotypes.

Pathologic ventricular hypertrophy in the offspring of diabetic mothers : a retrospective study

L'hypertrophie ventriculaire pathologique chez les nouveau-nés des mères diabétiques une étude rétrospective RESUME Objectif L'incidence du diabète chez les femmes enceintes ne cesse de croître, de même que les complications chez leurs nouveau-nés. C'est pourquoi, nous avons étudié la population de mères diabétiques suivies dans notre établissement entre les années 2003-2005 dans le but d'analyser spécifiquement le problème d'hypertrophie ventriculaire pathologique (HVP) chez les nouveau-nés de cette population. Méthode et résultats Dans notre étude rétrospective comprenant 87 grossesses de femmes diabétiques (92 nouveau-nés), 16 présentaient un diabète de type 1, 17 de type 2 et 54 ont développé un diabète gestationnel (DG). Le médian des hémoglobines glycquées (HbAlc) pour cette population est de 5.8% (5.3-6.5) : 17 avaient une HbAlc au-dessus de la norme, dont 2 souffrant d'une cardiomyopathie congénitale (CMC) et six d'une HVP. Un total de 75 nouveaux-nés étaient normaux, cinq avaient une CMC et 12 une HVP (1/12 décédé post-natalement, 1/12 mort-né, 2/12 nécessitant un accouchement prématuré, 8/12 normaux). Les 16 mères avec un diabète de type 1 accouchèrent de trois nouveau-nés avec une CMC et de 50% avec une HVP, comprenant un enfant décédé et un prématuré né par césarienne à cause d'une HVP. Dans le groupe des 17 nouveau-nés issus d'une mère connue pour un diabète de type 2, un cas présentait une CMC et 25% des cas une HVP. Parmi les 54 grossesses avec un DG, on dénombre un cas de CMC et un cas de HVP. Conclusion Les grossesses de mères souffrant d'un diabète de type 1 et de type 2 comportent toutes deux un risque augmenté de développement d'une HVP comparées à celles de mères ayant développé un diabète gestationnel. Les contrôles glycémiques sont insuffisants pour éviter la survenue d'une HVP. Comme aucun autre paramètre prédictif n'a pu été défini jusqu'alors, nous concluons qu'un suivi échographique rapproché de ces grossesses peut prévenir des complications périnatales sévères.

Clinical use of temporary percutaneous left ventricular assist devices.

Background: Temporary percutaneous left ventricular assist devices (TPLVAD) can be inserted and removed in awake patients. They substitute left ventricular function for a period of up to a few weeks and provide an excellent backup and bridge to recovery or decision. Methods: Retrospective analysis of 75 patients who received TPLVAD to treat cardiogenic shock (n = 49) or to facilitate high-risk percutaneous coronary intervention (PCI) (n = 26). Forty-two patients with cardiogenic shock and 16 patients with high-risk PCI received a TandemHeart and 7 patients and 10 patients, respectively, received an Impella Recover LP 2.5. Outcome and related complications up to 1 month are reported with reference to device depending function. Results: One-month survival was 53% in patients with shock and 96% in patients with PCI. Conclusion: TPLVADs can support the failing heart with acceptable risk. Outcome is better in prophylactic use than in patients with cardiogenic shock. (C) 2011 Wiley-Liss, Inc.

Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%.

AIMS: Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). METHODS AND RESULTS: One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). CONCLUSION: Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.

Unexpected left ventricular free-wall rupture following an aortic catheter-valve implantation.

Our experience with the Sapien trans-apical aortic valve (Edwards Lifesciences Inc., Irvine, CA, USA) has been straightforward without per-procedural mortality except in 1/16 consecutive cases who developed non-apical haemorrhage early after valve implantation. We describe the case of an 84-year-old female carrying a very high operative risk (logistic EuroScore of 44%), who underwent a trans-apical stent-valve implantation for severe and symptomatic aortic valve stenosis (23 mm). Due to massive blood loss, an emergency sternotomy and cannulation for cardiopulmonary bypass resuscitation were necessary to treat (without success) an unusual and unexpected subaortic left ventricular free-wall rupture that occurred few minutes after the stent-valve positioning and implantation. To the best of our knowledge, this is the first described case of a left ventricular free-wall rupture occurring after an otherwise non-complicated standard catheter-based aortic valve replacement.

Sustained improvement in left ventricular function after bone marrow derived cell therapy in patients with acute ST elevation myocardial infarction. A 5-year follow-up from the Stem Cell Transplantation in Ischaemic Myocardium Study.

BACKGROUND: Intracoronary injection of autologous bone marrow-derived mononucleated cells (BM-MNC) may improve LV function shortly after acute ST elevation myocardial infarction (STEMI), but little is known about the long-term durability of the treatment effect. METHODS: In a single-centre trial a total of 60 patients with acute anterior STEMI, successful reperfusion therapy and a left ventricular ejection fraction (LVEF) of <50% were screened for the study. 23 patients were actively treated with intracoronary infusion of BM-MNC within a median of 3 days. The open-label control group consisted of 19 patients who did not consent to undergo BM-MNC treatment but agreed to undergo regular clinical and echocardiographic follow-up for up to 5 years after AMI. RESULTS: Whereas at 4 months there was no significant difference between the increase in LVEF in the BM-MNC group and the control group (+7.0%, 95%CI 3.6; 10.4) vs. +3.9%, 95%CI -2.1; 10), the absolute increase at 5 years remained stable in the BM-MNC but not in the control group (+7.95%, 95%CI 3.5; 12.4 vs. -0.5%, 95%CI -5.4; 4.4; p for interaction between groups = 0.035). DISCUSSION: In this single-centre, open-labelled study, intracoronary administration of BM-MNC is feasible and safe in the short term. It is also associated with sustained improvement of left ventricular function in patients with acute myocardial infarction, encouraging phase III studies to examine the potential BM-MNC effect on clinical outcome.

Numerical simulation of left ventricular assist device implantations: comparing the ascending and the descending aorta cannulations.

In this work we present numerical simulations of continuous flow left ventricle assist device implantation with the aim of comparing difference in flow rates and pressure patterns depending on the location of the anastomosis and the rotational speed of the device. Despite the fact that the descending aorta anastomosis approach is less invasive, since it does not require a sternotomy and a cardiopulmonary bypass, its benefits are still controversial. Moreover, the device rotational speed should be correctly chosen to avoid anomalous flow rates and pressure distribution in specific location of the cardiovascular tree. With the aim of assessing the differences between these two approaches and device rotational speed in terms of flow rate and pressure waveforms, we set up numerical simulations of network of one-dimensional models where we account for the presence of an outflow cannula anastomosed to different locations of the aorta. Then, we use the resulting network to compare the results of the two different cannulations for several stages of heart failure and different rotational speed of the device. The inflow boundary data for the heart and the cannulas are obtained from a lumped parameters model of the entire circulatory system with an assist device, which is validated with clinical data. The results show that ascending and descending aorta cannulations lead to similar waveforms and mean flow rate in all the considered cases. Moreover, regardless of the anastomosis region, the rotational speed of the device has an important impact on wave profiles; this effect is more pronounced at high RPM.