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Background LV global longitudinal strain (GLS) is significantly altered in HFpEF and is a powerful predictor of outcome according to a recent meta-analysis. Aim We sought to determine the evolution of GLS across the spectrum of AHA HF stages and to analyze the correlation of GLS with other clinical, biological and imaging variables and its prognostic value in HFpEF. Methods GLS was assessed by 2D speckle-tracking echocardiography in 172 patients with HFpEF stage C (78 ± 10 yrs, 38%men), 22 stage B (73 ± 10 yrs, 32%men), 56 stage A (63 ± 16 yrs, 52% men) and 20 healthy volunteers (38 ± 12 yrs, 55% men). Impaired GLS was defined as −16.6%, corresponding to 2 SD below the mean value of age and sex matched controls. All patients underwent 2D echo and cMR. Patients were followed up for a composite outcome of mortality and first HF hospitalization. Results Mean GLS was −20.1 ± 1.0%, −19.8 ± 1.6%, −19.1 ± 2.6% and −16.6 ± 3.0% in volunteers, stage A, stage B and stage C respectively (P for trend Fig. 1 ). In HFpEF stage C, 86 patients (50%) had an impaired GLS. They had higher NTproBNP (P = 0.002), higher sST2 (P = 0.023), higher incidence of AF (55% vs. 36%, P = 0.014), lower LVEF (P Conclusion There is a continuum in GLS impairment across the spectrum of AHA HF stages confirming the role of a subclinical myocardial dysfunction in HFpEF. Impaired GLS was associated with RV dysfunction and NTproBNP but not with clinical outcomes in HFpEF.

Introduction Right ventricle strain has emerged as an accurate tool for RV function assessment and is a strong predictor of survival in HFrEF. The impact of RV strain assessed by cMR in HFpEF is unknown. Objective We sought to analyze RV strain by cMR in controls and HFpEF and to analyze its prognostic value. Methods Between January 2015 and June 2017, we prospectively enrolled 100 consecutive patients with HFpEF (79 ± 8 years, 59% women) and 64 controls (56 ± 20 years, 52% women). All patients underwent 2D echo and 3Tesla cMR in sinus rhythm. A four-chamber view was analyzed by 2D feature tracking to evaluate the global longitudinal strain of RV (RV-GLS). HFpEF patients were followed up for a combined outcome of all-cause mortality and first HF hospitalization. Results In HFpEF, mean RV-GLS was significantly lower than in controls (−14.6 ± 4.6% vs. −17.0 ± 3.9%; P = 0.007) ( Fig. 1 ). Due to poor tracking quality, 28 controls (44%) and 19 HFpEF patients (19%) were excluded from the analysis. In univariate linear regression analysis, NTproBNP (R = 0.36, P = 0.001), E wave velocity (R = 0.29, P = 0.001), E/e’ ratio (R = 0.28, P = 0.002), RV fractional area change (R = −0.29, P = 0.001), TAPSE (R = −0.24, P = 0.006), indexed LA volume (R = 0.27, P = 0.003), LVEF (R = −0.32, P = 0.001), indexed LV mass (R = 0.36, P = 0.001), RVEF by cMR (R= −0.45, P Conclusion RV-GLS assessed by cMR feature tracking is significantly different between controls and HFpEF patients and is associated with RVEF and NTproBNP. However, RV GLS was not associated with poor outcome in HFpEF.

Background Aortic valve replacement (AVR) is a class I indication in asymptomatic patients with severe AS and LVEF Purpose The aim of this study was to determine the best left ventricular ejection fraction (LVEF) cut-off to predict long-term mortality in patients with asymptomatic or minimally symptomatic severe aortic stenosis (AS) and LVEF ≥ 50% under conservative management and after surgical correction of AS. Methods This analysis includes 1678 patients with preserved (≥50%) LVEF and no or minimal symptoms, diagnosed with severe AS. The population was divided into 3 groups: LVEF Results Five-year survival rate was 72 ± 2% for patients with LVEF ≥60%, 74 ± 2% for patients with LVEF between 55 and 59% and 59 ± 4% for patients with LVEF Conclusion LVEF is a powerful predictor of survival in a population of AS patients with no or minimal symptoms at diagnosis and LVEF ≥ 50%. Patients with LVEF

OBJECTIVES: We describe the first report of a transcatheter Sapien implantation in a native tricuspid valve after multiple failed surgical repairs with a lack of prosthetic material and radiographic landmarks. METHODS AND RESULTS: A 47-year old female underwent multiple valve repairs and replacements including three tricuspid valve repairs without surgical ring or bioprosthesis implantation. She developed signs of right heart failure associated with a mixed tricuspid disease combining a severe stenosis and regurgitation. After surgical turn down, a revalvulation using a transcatheter approach was attempted. The challenges in this case were the absence of a stiff region to anchor the percutaneous valve, the lack of radiographic landmarks and the difficulties of precise annulus measurements. The applied strategy was -under general anesthesia and extracorporeal membrane oxygenation-: balloon sizing, prestenting of the tricuspid annulus using covered stents followed by Sapien valve implantation through the femoral vein under fluoroscopy and transoesophageal echocardiography (TEE). The procedure was successfull, solving the tricuspid leak and stenosis (peak gradient from 22 to 3 mm Hg) using two Sapien for a perfect positioning. It was complicated by pulmonary bleeding due to a distal wire exit, treated successfully by coil embolization. The clinical and echocardiographic outcome was good up to 5 months. CONCLUSIONS: Transcatheter Sapien valve implantation in a native tricuspid valve after failed multiple surgical repairs is feasible by the femoral vein. Technical challenges due to the lack of rigid landing zone and fluoroscopic markers were solved by prestenting and valve implantation under bi-plane fluoroscopic and TEE guidance.

Background— Recent works using echocardiography suggested that low gradient (LG), low flow (LF) aortic stenosis (AS) has more pronounced left ventricular (LV) concentric remodeling, smaller LV cavity size, and more interstitial fibrosis compared with high gradient (HG) normal flow (NF) AS. Therefore, we evaluated the accuracy of echocardiographic measurements and compared remodeling and fibrosis in different types of AS by cardiac magnetic resonance (CMR). Methods and Results— A total of 128 patients (73±11 years of age; 75 men) with aortic valve area (AVA) 2 /m 2 and ejection fraction >50% by echocardiography underwent CMR to measure planimetric AVA, phase-contrast indexed stroke volume, LV mass, and focal fibrosis. Using 2 by echocardiography as criteria for LG and LF, 69 (54%) patients were HG/NF, 28 (22%) HG/LF, 17 (13%) LG/NF, and 14 (11%) LG/LF AS. LV outflow tract area, indexed stroke volume, and AVA correlated well between echocardiography and CMR ( r =0.7, 0.61, and 0.65, respectively; P 2 /m 2 ) and LG/NF (0.61±0.08 cm 2 /m 2 ) than in HG/LF (0.46±0.07 cm 2 /m 2 ; P 2 ) and LG/NF (81±18 g/m 2 ) than in HG/LF (100±27 g/m 2 ; P Conclusions— CMR confirmed overall accuracy of echocardiographic classification of AS but demonstrated that LG/LF and LG/NF AS have larger AVA, less LV hypertrophy, and similar focal fibrosis compared with HG/LF AS. This challenges the view that LG/LF AS is a more advanced state of AS.

Eukaryotic elongation factor 2 (eEF-2) and mammalian target of rapamycin (mTOR)–p70 ribosomal protein S6 kinase (p70S6K) signaling pathways control protein synthesis and are inhibited during myocardial ischemia. Intracellular acidosis and AMP-activated protein kinase (AMPK) activation, both occurring during ischemia, have been proposed to participate in this inhibition. We evaluated the contribution of AMPKα2, the main cardiac AMPK catalytic subunit isoform, in eEF2 and mTOR–p70S6K regulation using AMPKα2 KO mice. Hearts were perfused ex vivo with or without insulin, and then submitted or not to ischemia. Insulin pre-incubation was necessary to activate mTOR–p70S6K and evaluate their subsequent inhibition by ischemia. Ischemia decreased insulin-induced mTOR–p70S6K phosphorylation in WT and AMPKα2 KO mice to a similar extent. This AMPKα2-independent p70S6K inhibition correlated well with the inhibition of PKB/Akt, located upstream of mTOR–p70S6K and can be mimicked in cardiomyocytes by decreasing pH. By contrast, ischemia-induced inhibitory phosphorylation of eEF-2 was drastically reduced in AMPKα2 KO mice. Interestingly, AMPKα2 also played a role under normoxia. Its deletion increased the insulin-induced p70S6K stimulation. This p70S6K over-stimulation was associated with a decrease in inhibitory phosphorylation of Raptor, an mTOR partner identified as an AMPK target. In conclusion, AMPKα2 controls cardiac p70S6K under normoxia and regulates eEF-2 but not the mTOR–p70S6K pathway during ischemia. This challenges the accepted notion that mTOR–p70S6K is inhibited by myocardial ischemia mainly via an AMPK-dependent mechanism.

Objectives This study sought to evaluate the feasibility and safety of autologous bone marrow-derived and cardiogenically oriented mesenchymal stem cell therapy and to probe for signs of efficacy in patients with chronic heart failure. Background In pre-clinical heart failure models, cardiopoietic stem cell therapy improves left ventricular function and blunts pathological remodeling. Methods The C-CURE (Cardiopoietic stem Cell therapy in heart failURE) trial, a prospective, multicenter, randomized trial, was conducted in patients with heart failure of ischemic origin who received standard of care or standard of care plus lineage-specified stem cells. In the cell therapy arm, bone marrow was harvested and isolated mesenchymal stem cells were exposed to a cardiogenic cocktail. Derived cardiopoietic stem cells, meeting release criteria under Good Manufacturing Practice, were delivered by endomyocardial injections guided by left ventricular electromechanical mapping. Data acquisition and analysis were performed in blinded fashion. The primary endpoint was feasibility/safety at 2-year follow-up. Secondary endpoints included cardiac structure/function and measures of global clinical performance 6 months post-therapy. Results Mesenchymal stem cell cocktail-based priming was achieved for each patient with the dose attained in 75% and delivery without complications in 100% of cases. There was no evidence of increased cardiac or systemic toxicity induced by cardiopoietic cell therapy. Left ventricular ejection fraction was improved by cell therapy (from 27.5 +/- 1.0% to 34.5 +/- 1.1%) versus standard of care alone (from 27.8 +/- 2.0% to 28.0 +/- 1.8%, p < 0.0001) and was associated with a reduction in left ventricular end-systolic volume (-24.8 +/- 3.0 ml vs. -8.8 +/- 3.9 ml, p < 0.001). Cell therapy also improved the 6-min walk distance (+62 +/- 18 m vs. -15 +/- 20 m, p < 0.01) and provided a superior composite clinical score encompassing cardiac parameters in tandem with New York Heart Association functional class, quality of life, physical performance, hospitalization, and event-free survival. Conclusions The C-CURE trial implements the paradigm of lineage guidance in cell therapy. Cardiopoietic stem cell therapy was found feasible and safe with signs of benefit in chronic heart failure, meriting definitive clinical evaluation. (C-Cure Clinical Trial; NCT00810238) (C) 2013 by the American College of Cardiology Foundation

We have recently shown that valve sparing reimplantation (VSR) improves the durability of bicuspid aortic valve repair in comparison with subcommissural annuloplasty. The aim of this study was to assess the degree of annular reduction provided by these techniques and to correlate these findings with repair durability.From 1995 to 2010, 161 patients underwent bicuspid valve repair. We included only patients with subcommissural annuloplasty or reimplantation having intraoperative pre- and post-repair transoesophageal echocardiography images. Pre- and post-repair ventriculo-aortic junction (VAJ) diameters were measured on long axis views. Inclusion criteria were met by 53 patients with subcommissual annuloplasty and 65 with reimplantation. Median follow-up was 53 months in the subcommissual annuloplasty group and 42 months in the reimplantation group. Follow-up completeness was 100% in subcommissural annuloplasty and 94% in reimplantation.There was no operative or late mortality. Mean preoperative VAJ was similar in both groups (reimplantation: 28 ± 3 mm vs subcommissural annuloplasty: 28 ± 3, P = 0.16). Preoperative VAJ was larger in patients40 years and with aortic regurgitation (AR) ≥ 3+ (P0.01). Mean postoperative VAJ was smaller in reimplantation compared with subcommissural annuloplasty (21 ± 2 mm vs 24 ± 3 mm, P0.01). In univariate analyses, subcommissural annuloplasty, preoperative VAJ ≥ 30 mm, postoperative VAJ ≥ 25 mm and cusp repair with patch were predictive of recurrent AR1+. In the subcommissural annuloplasty group, VAJ≥ 30 mm preoperatively and ≥ 25 mm postoperatively were associated with decreased 6 years freedom from recurrent AR1+ (30 mm: 74% vs ≥ 30 mm: 39%, P = 0.01;25 mm: 80% vs ≥ 25 mm 31%, P = 0.02) In the reimplantation group, VAJ dimension had no effect on recurrent AR1+ (P = 0.93).In bicuspid aortic valve repair, the circumferential annuloplasty of VSR offers greater reduction of VAJ compared with the non-circumferential annuloplasty provided by the subcommissural annuloplasty. The degree and extent of VAJ reduction in reimplantation seem to be factors among others that positively influence repair durability particularly in patients with a large VAJ (≥ 30 mm).

International audience; Aims In degenerative mitral regurgitation (DMR), lack of mortality scores predicting death favours misperception of individual patients' risk and inappropriate decision-making. Methods and results The Mitral Regurgitation International Database (MIDA) registries include 3666 patients (age 66 +/- 14 years; 70% males; follow-up 7.8 +/- 5.0 years) with pure, isolated, DMR consecutively diagnosed by echocardiography at tertiary (European/North/South-American) centres. The MIDA Score was derived from the MIDA-Flail-Registry (2472 patients with DMR and flail leaflet-Derivation Cohort) by weighting all guideline-provided prognostic markers, and externally validated in the MIDA-BNP-Registry (1194 patients with DMR and flail leaflet/prolapse-Validation Cohort). The MIDA Score ranged from 0 to 12 depending on accumulating risk factors. In predicting total mortality post-diagnosis, the MIDA Score showed excellent concordance both in Derivation Cohort (c = 0.78) and Validation Cohort (c = 0.81). In the whole MIDA population (n = 3666 patients), 1-year mortality with Scores 0, 7-8, and 11-12 was 0.4, 17, and 48% under medical management and 1, 7, and 14% after surgery, respectively (P < 0.001). Five-year survival with Scores 0, 7-8, and 11-12 was 98 +/- 1, 57 +/- 4, and 21 +/- 10% under medical management and 99 +/- 1, 82 +/- 2, and 57 +/- 9% after surgery (P < 0.001). In models including all guideline-provided prognostic markers and the EuroScoreII, the MIDA Score provided incremental prognostic information (P

International audience; BackgroundαVβ3-integrin is expressed by activated endothelial cells and macrophages in atherosclerotic plaques and may represent a valuable marker of high-risk plaques. We evaluated 99mTc-maraciclatide, an integrin-specific tracer, for imaging vascular inflammation in atherosclerotic lesions in mice.MethodsApolipoprotein E-negative (ApoE−/−) mice on a Western diet (n = 10) and normally fed adult C57BL/6 control mice (n = 4) were injected with 99mTc-maraciclatide (51.8 ± 3.7 MBq). A blocking peptide was infused in three ApoE−/− mice; this condition served as another control. After 90 min, the animals were imaged via single-photon emission computed tomography (SPECT). While maintained in the same position, the mice were transferred to computed tomography (CT) to obtain contrast-enhanced images of the aortic arch. Images from both modalities were fused, and signal was quantified in the aortic arch and in the vena cava for subtraction of blood-pool activity. The aorta was carefully dissected after imaging for gamma counting, autoradiography, and histology.ResultsTracer uptake was significantly higher in ApoE−/− mice than in both groups of control mice (1.56 ± 0.33 vs. 0.82 ± 0.24 vs. 0.98 ± 0.11, respectively; P = 0.006). Furthermore, higher tracer activity was detected via gamma counting in the aorta of hypercholesterolemic mice than in both groups of control mice (1.52 ± 0.43 vs. 0.78 ± 0.19 vs. 0.47 ± 0.31 99mTc-maraciclatide %ID/g, respectively; P = 0.018). Autoradiography showed significantly higher tracer uptake in the atherosclerotic aorta than in the control aorta (P = 0.026). Finally, in the atherosclerotic aorta, immunostaining indicated that the integrin signal came predominantly from macrophages and was correlated with the macrophage CD68 immunomarker (r = 0.73).Conclusions99mTc-maraciclatide allows in vivo detection of inflamed atherosclerotic plaques in mice and may represent a non-invasive approach for identifying high-risk plaques in patients.

High plasma leucine levels strongly correlate with type 2 diabetes. Studies of muscle cells have suggested that leucine alters the insulin response for glucose transport by activating an insulin-negative feedback loop driven by the mammalian target of rapamycin/p70 ribosomal S6 kinase (mTOR/p70S6K) pathway. Here, we examined the molecular mechanism involved in leucine’s action on cardiac glucose uptake. Leucine was indeed able to curb glucose uptake after insulin stimulation in both cultured cardiomyocytes and perfused hearts. Although leucine activated mTOR/p70S6K, the mTOR inhibitor rapamycin did not prevent leucine’s inhibitory action on glucose uptake, ruling out the contribution of the insulin-negative feedback loop. α-Ketoisocaproate, the first metabolite of leucine catabolism, mimicked leucine’s effect on glucose uptake. Incubation of cardiomyocytes with [13C]leucine ascertained its metabolism to ketone bodies (KBs), which had a similar negative impact on insulin-stimulated glucose transport. Both leucine and KBs reduced glucose uptake by affecting translocation of glucose transporter 4 (GLUT4) to the plasma membrane. Finally, we found that leucine elevated the global protein acetylation level. Pharmacological inhibition of lysine acetyltransferases counteracted this increase in protein acetylation and prevented leucine’s inhibitory action on both glucose uptake and GLUT4 translocation. Taken together, these results indicate that leucine metabolism into KBs contributes to inhibition of cardiac glucose uptake by hampering the translocation of GLUT4-containing vesicles via acetylation. They offer new insights into the establishment of insulin resistance in the heart. NEW & NOTEWORTHY Catabolism of the branched-chain amino acid leucine into ketone bodies efficiently inhibits cardiac glucose uptake through decreased translocation of glucose transporter 4 to the plasma membrane. Leucine increases protein acetylation. Pharmacological inhibition of acetylation reverses leucine’s action, suggesting acetylation involvement in this phenomenon. Listen to this article’s corresponding podcast at http://ajpheart.podbean.com/e/leucine-metabolism-inhibits-cardiac-glucose-uptake/ .

Aims Although recommended by current guidelines, adoption of three-dimensional echocardiographic (3DE) chamber quantification in clinical practice has lagged because of time-consuming analysis. We recently validated an automated algorithm that measures left atrial (LA) and left ventricular (LV) volumes and ejection fraction (EF). This study aimed to determine the accuracy and reproducibility of these measurements in a multicentre setting. Methods and results 180 patients underwent 3DE imaging (Philips) at six sites. Images were analysed using automated HeartModel (HM) software with endocardial border correction when necessary and by manual tracing. Measurements were performed by each site and by the Core Laboratory (CL) as the reference. Inter-technique comparisons included HM measurements by the sites against manual tracing by CL, and showed strong correlations (r-values: LVEDV: 0.97, LVESV: 0.97, LVEF: 0.88, LAV: 0.96), with the automated technique slightly underestimating LV volumes (biases: LVEDV: -14 ± 20 ml, LVESV: -6 ± 20 ml), LVEF (-2 ± 7%) and LAV (-9 ± 10 ml). Intra-technique comparisons included HM measurements by the sites against CL, with and without corrections. Corrections were unnecessary or minimal in most patients, and improved the measurements only modestly. Comparisons without corrections showed perfect agreement for all parameters. With corrections, correlations were better (r-values: LVEDV: 0.99, LVESV: 0.99, LVEF: 0.94, LAV: 0.99) and biases (LVEDV: -8 ± 12 ml, LVESV: -6 ± 12 ml, LVEF: 1 ± 5%, LAV: -10 ± 6 ml) smaller than in inter-technique comparison. All automated measurements with corrections were more reproducible than manual measurements. Conclusion Automated 3DE analysis of left-heart chambers is an accurate alternative to conventional manual methodology, which yields almost the same values across laboratories and is more reproducible. This technique may contribute towards full integration of 3DE quantification into clinical routine.

Studies suggesting that B-type natriuretic peptide (BNP) may predict outcomes of mitral regurgitation (MR) are plagued by small size, inconsistent etiologies, and lack of accounting for shifting normal BNP ranges with age and sex.This study assessed the effect of BNP activation on mortality in a large, multicenter cohort of patients with degenerative MR.In 1,331 patients with degenerative MR, BNP was prospectively measured at diagnosis and expressed as BNPratio (ratio to upper limit of normal for age, sex, and assay). Initial surgical management was performed within 3 months of diagnosis in 561 patents.The cohort had a mean age of 64 ± 15 years, was 66% male, and had a mean ejection fraction 64 ± 9%, mean regurgitant volume 67 ± 31 ml, and low mean Charlson comorbidity index of 1.09 ± 1.76. Median BNPratio was 1.01 (25th and 75th percentiles: 0.42 to 2.36). Overall, BNPratio was a powerful, independent predictor of mortality (hazard ratio: 1.33 [95% confidence interval: 1.15 to 1.54]; p 0.0001), whereas absolute BNP was not (p = 0.43). In patients who were initially treated medically (n = 770; 58%), BNPratio was a powerful, independent, and incremental predictor of mortality after diagnosis (hazard ratio: 1.61 [95% confidence interval: 1.34 to 1.93]; p 0.0001). Higher BNP activation was associated with higher mortality (p 0.0001). All subgroups, particularly severe MR, incurred similar excess mortality with BNP activation. After initial surgical treatment (n = 561, 42%) BNP activation did not impose excess long-term mortality (p = 0.23).In patients with degenerative MR, BNPratio is a powerful, independent, and incremental predictor of long-term mortality under medical management. BNPratio should be incorporated into the routine clinical assessment of patients with degenerative MR.

BACKGROUND: In our ageing society, valvular heart diseases (VHD) have become an increasing public health problem. However, the lack of studies describing the impact of these diseases on the outcome of very old subjects makes it difficult to appreciate their real clinical burden. METHODS: Prospective, observational, population-based cohort study in Belgium. Five hundred fifty six subjects aged 80 years and older were followed up for 5.1 ± 0.25 years for mortality and 3.0 ± 0.25 years for hospitalization. Echocardiograms were performed at baseline. The Cumulative Illness Rating Scale (CIRS) was calculated for each subject. RESULTS: The prevalence of moderate-to-severe VHD was 17% (n = 97). Mitral stenosis was more prevalent in women and an age-dependent increase of the prevalence of severe aortic stenosis was seen. The overall disease burden was higher in participants with VHD (median CIRS 3 [IQR 3-5] vs 4 [IQR 3-6] (P = 0.008)). Moderate-to-severe VHD, and more specifically mitral stenosis and aortic stenosis, was found to be an independent predictor of both all-cause (HR 1.42 (95% CI 1.04-1.95)) and cardiovascular mortality (HR 2.13 (95% CI 1.38-3.29)). Moderate-to-severe VHD was also found to be an independent predictor of the need for a first unplanned hospitalization (HR 1.43 (95% CI 1.06-1.94)). CONCLUSIONS: A high prevalence of moderate-to-severe VHD was found in the very old. Moderate-to-severe VHD was identified as an independent risk factor for all-cause and cardiovascular mortality and as well for unplanned hospitalizations, independent of other structural cardiac abnormalities, ventricular function and major co-morbidities. Query date: 2019-12-23 16:38:43 ispartof: Bmc Cardiovascular Disorders vol:16 issue:1 ispartof: location:England status: published

OBJECTIVES: Different diagnostic algorithms for non-acute heart failure (HF) exist. Our aim was to compare the ability of these algorithms to identify HF in symptomatic patients aged 80 years and older and identify those patients at highest risk for mortality. DESIGN: Diagnostic accuracy and validation study. SETTING: General practice, Belgium. PARTICIPANTS: 365 patients with HF symptoms aged 80 years and older (BELFRAIL cohort). Participants underwent a full clinical assessment, including a detailed echocardiographic examination at home. OUTCOME MEASURES: The diagnostic accuracy of 4 different algorithms was compared using an intention-to-diagnose analysis. The European Society of Cardiology (ESC) definition of HF was used as the reference standard for HF diagnosis. Kaplan-Meier curves for 5-year all-cause mortality were plotted and HRs and corresponding 95% CIs were calculated to compare the mortality risk predicting abilities of the different algorithms. Net reclassification improvement (NRI) was calculated. RESULTS: The prevalence of HF was 20% (n=74). The 2012 ESC algorithm yielded the highest sensitivity (92%, 95% CI 83% to 97%) as well as the highest referral rate (71%, n=259), whereas the Oudejans algorithm yielded the highest specificity (73%, 95% CI 68% to 78%) and the lowest referral rate (36%, n=133). These differences could be ascribed to differences in N-terminal probrain natriuretic peptide cut-off values (125 vs 400 pg/mL). The Kelder and Oudejans algorithms exhibited NRIs of 12% (95% CI 0.7% to 22%, p=0.04) and 22% (95% CI 9% to 32%, p

BACKGROUND: Little is known about the relationship between cardiac dysfunction and poor functioning in the elderly. This study sought to describe the prevalence of cardiac dysfunction in the very elderly and to investigate the correlation between echocardiographic abnormalities and indicators of poor functioning. METHODS: A cross-sectional analysis within the BELFRAIL (BF(C80+)) study of 567 subjects aged 80years and older. The clinical research assistant performed an examination including performance testing, questionnaires and technical examinations. Echocardiography was performed at the subject’s home by a cardiologist using a portable system. RESULTS: The mean age of the participants was 84.7years and 62.9% were women. Severe cardiac dysfunction was found in 19.3% and was defined as systolic dysfunction (5.8%), valvular heart disease (10.4%) or isolated severe diastolic dysfunction (3.1%). Severe cardiac dysfunction showed to be an independent identifier of poor performance (OR 1.8 (95% CI 1.1-3.2)), a low LAPAQ (LASA Physical Activity Questionnaire) score (OR 1.9 (95% CI 1.2-3.3)) and a high GDS-15 (Geriatric Depression Scale) score (OR 1.7 (95% CI 1.0-2.9)). This relationship was mainly explained by the independent correlation between aortic stenosis and poor functioning. Classic indicators of systolic and diastolic dysfunction were not able to identify participants with poor functioning. CONCLUSION: This study shows the very elderly represent a heterogeneous group of subjects with a high prevalence of comorbidities, among whom poor functioning might be triggered by multiple causes. Severe cardiac dysfunction, and more specifically aortic stenosis, showed an independent relationship with poor functioning.

Heart failure of ischemic origin has become increasingly common over the last decade because of the improved survival of patients with acute myocardial infarction. Revascularization with coronary bypass grafting or percutaneous coronary intervention plays a pivotal role in patients with ischemic cardiomyopathy, although these interventions are often associated with relatively high peri-procedural risk. The pathophysiological substrate of ischemic cardiomyopathy is heterogeneous, varying from predominantly hibernating myocardium to irreversible scarring. There is evidence to suggest that patients with hibernating myocardium benefit most from revascularization, whereas medical therapy is associated with an adverse prognosis. Therefore, noninvasive testing is recommended by relevant guidelines to guide optimal management in these patients. However, the role of noninvasive testing has recently been challenged. There are various imaging modalities available that provide information on different aspects of the disease, and therefore, they differ significantly in sensitivity and specificity. In clinical practice, choosing among the different imaging modalities can be difficult. Cardiac magnetic resonance has evolved into a comprehensive modality that can accurately determine the amount of hibernating myocardium as well as the presence and degree of myocardial ischemia and the extent of the scar. This paper reviews the indications, accuracy, and clinical utility of the available imaging techniques, with a special focus on cardiac magnetic resonance in ischemic cardiomyopathy, and provides an outlook on how this field might evolve in the future.

AIMS: Exposure to high glucose (HG) stimulates reactive oxygen species (ROS) production by NADPH oxidase in cardiomyocytes, but the underlying mechanism remains elusive. In this study, we have dissected the link between glucose transport and metabolism and NADPH oxidase activation under hyperglycaemic conditions. METHODS AND RESULTS: Primary cultures of adult rat cardiomyocytes were exposed to HG concentration (HG, 21 mM) and compared with the normal glucose level (LG, 5 mM). HG exposure activated Rac1GTP and induced p47phox translocation to the plasma membrane, resulting in NADPH oxidase (NOX2) activation, increased ROS production, insulin resistance, and eventually cell death. Comparison of the level of O-linked N-acetylglucosamine (O-GlcNAc) residues in LG- and HG-treated cells did not reveal any significant difference. Inhibition of the pentose phosphate pathway (PPP) by 6-aminonicotinamide counteracted ROS production in response to HG but did not prevent Rac-1 upregulation and p47phox translocation leading to NOX2 activation. Modulation of glucose uptake barely affected oxidative stress and toxicity induced by HG. More interestingly, non-metabolizable glucose analogues (i.e. 3-O-methyl-d-glucopyranoside and α-methyl-d-glucopyranoside) reproduced the toxic effect of HG. Inhibition of the sodium/glucose cotransporter SGLT1 by phlorizin counteracted HG-induced NOX2 activation and ROS production. CONCLUSION: Increased glucose metabolism by itself does not trigger NADPH oxidase activation, although PPP is required to provide NOX2 with NADPH and to produce ROS. NOX2 activation results from glucose transport through SGLT1, suggesting that an extracellular metabolic signal transduces into an intracellular ionic signal.

The AMP-activated protein kinase (AMPK) is known to increase cardiac insulin sensitivity on glucose uptake. AMPK also inhibits the mammalian target of rapamycin (mTOR)/p70 ribosomal S6 kinase (p70S6K) pathway. Once activated by insulin, mTOR/p70S6K phosphorylates insulin receptor substrate-1 (IRS-1) on serine residues, resulting in its inhibition and reduction of insulin signaling. AMPK was postulated to act on insulin by inhibiting this mTOR/p70S6K-mediated negative feedback loop. We tested this hypothesis in cardiomyocytes. The stimulation of glucose uptake by AMPK activators and insulin correlated with AMPK and protein kinase B (PKB/Akt) activation, respectively. Both treatments induced the phosphorylation of Akt substrate 160 (AS160) known to control glucose uptake. Together, insulin and AMPK activators acted synergistically to induce PKB/Akt overactivation, AS160 overphosphorylation, and glucose uptake overstimulation. This correlated with p70S6K inhibition and with a decrease in serine phosphorylation of IRS-1, indicating the inhibition of the negative feedback loop. We used the mTOR inhibitor rapamycin to confirm these results. Mimicking AMPK activators in the presence of insulin, rapamycin inhibited p70S6K and reduced IRS-1 phosphorylation on serine, resulting in the overphosphorylation of PKB/Akt and AS160. However, rapamycin did not enhance the insulin-induced stimulation of glucose uptake. In conclusion, although the insulin-sensitizing effect of AMPK on PKB/Akt is explained by the inhibition of the insulin-induced negative feedback loop, its effect on glucose uptake is independent of this mechanism. This disconnection revealed that the PKB/Akt/AS160 pathway does not seem to be the rate-limiting step in the control of glucose uptake under insulin treatment.

Cardiovascular diseases are still the primary causes of mortality in the United States and in Western Europe. Arterial thrombosis is triggered by a ruptured atherosclerotic plaque and precipitates an acute vascular event, which is responsible for the high mortality rate. These rupture-prone plaques are called “vulnerable plaques.” During the past decades, much effort has been put toward accurately detecting the presence of vulnerable plaques with different imaging techniques. In this review, we provide an overview of the currently available invasive and noninvasive imaging modalities used to detect vulnerable plaques. We will discuss the upcoming challenges in translating these techniques into clinical practice and in assigning them their exact place in the decision-making process.

Urocortin-1 (UCN), a member of the corticotropin-releasing factor, is a cardioprotective peptide, and is also involved in cardiac hypertrophy. The involvement of GSK-3β, a pivotal kinase in cardiac hypertrophy, in response to UCN is not yet documented. Cardiomyocytes from adult rats were stimulated for 48 h with UCN. Cell size, protein, and DNA contents were determined. Phosphorylated and total forms GSK-3β and the total amount of β-catenin were quantified by Western immunoblots. The effects of astressin, a UCN competitive receptor antagonist, were also evaluated. UCN increased cell size and the protein-to-DNA ratio, in accordance with a hypertrophic response. This effect was associated with increased phosphorylation of GSK-3β and marked accumulation of β-catenin, a downstream element to GSK-3β. All these effects were prevented by astressin and LY294002, an inhibitor of the phosphatidyl-inositol-3-kinase. UCN-induced cardiomyocytes hypertrophy is associated with regulation of GSK-3β, a pivotal kinase involved in cardiac hypertrophy, in a PI3K-dependent manner. Furthermore, the pharmacological blockade of UCN receptors was able to prevent UCN-induced hypertrophy, which leads to inhibition of the Akt/GSK-3β pathway.

Aortic stenosis (AS) is a common valve disease in octogenarians. Previous studies have shown that aortic valve replacement (AVR) is frequently not performed in these patients. This study investigated the incidence, determinants, and prognostic impact of AVR refusal or denial in these patients.Between 2000 and 2007, 163 octogenarians (mean age, 84 ± 3 years) with severe AS and an indication for operation according to guidelines were prospectively included in an echocardiographic registry. Among these, 97 underwent AVR, and 66 were treated conservatively.Logistic regression analysis identified older age, a lower transaortic pressure gradient, a larger aortic valve area, and the presence of diabetes as independent predictors of AVR refusal or denial. Patients who underwent AVR had a 30-day mortality of 9%. Overall 5-year survival was 66% in AVR patients vs 31% in those treated conservatively (log rank p0.001 vs AVR). After adjustment for the propensity score, patients undergoing AVR still had a better outcome than conservatively treated patients (hazard ratio, 0.56; 95% confidence interval, 0.29 to 0.91; p = 0.022). In addition to the therapeutic decision, Cox regression analysis also identified low body weight, New York Heart Association class III/IV, and the logistic European System for Cardiac Operative Risk Evaluation as independent predictors of outcome in the overall series.About 40% of octogenarians with severe AS and a definite indication for operation either refuse or are denied AVR. AVR refusal or denial has a profound impact on long-term prognosis, resulting in a twofold excess mortality, even after adjustment for the propensity score.

Mobilization of stem cells and progenitor cells from the bone marrow (BM) into the peripheral blood (PB) by granulocyte-colony-stimulating factor (G-CSF) is being investigated for cardiac regeneration in ischemic heart disease. However, hematopoietic (HPC), mesenchymal (MPC) and endothelial (EPC) progenitor mobilization have not been optimized and the effect of G-CSF on myocardial perfusion and cardiac function in a normal heart has never been studied.Normal mice were injected daily for 1-10 days with subcutaneous recombinant human G-CSF. PB and BM were evaluated for HPC and EPC by flow cytometry and HPC and MPC by hematopoietic (CFU-GM) and mesenchymal (CFU-F) colony assays. Echocardiography, microSPECT imaging, cardiac catheterization and immunohistochemistry were performed in mice treated for 10 days.HPC and CFU-GM in PB peaked after 2 days, CFU-F after 4 days and EPC after 3 days. Thereafter, while HPC temporally decreased before showing a second peak, EPC remained detectable only at low levels. In BM, hematopoietic stem cells (HSC) and CFU-GM did not increase much overall but peaked twice on days 2 and 7. EPC (peak on day 7) production increased in the BM, but CFU-F formation declined considerably after day 2. G-CSF enhanced myocardial perfusion and vascularization but impaired hemodynamic performance of the heart through apparently increased ventricular wall rigidity.G-CSF induces the mobilization of HPC, EPC and CFU-F progenitors in PB according to very different patterns, and has a significant impact on perfusion and function of the normal heart.

ObjectivesTo better understand the quantitative relationship of recovery of regional and global dysfunction after revascularization in chronic infarcts with variable transmural extent of necrosis by delayed enhanced cardiac magnetic resonance.BackgroundStudies relating transmurality of delayed enhanced magnetic resonance to functional recovery in dysfunctional myocardium using semiquantitative Likert scales have demonstrated the intermediate likelihood (50% probability) of recovery of dysfunction in subendocardial scars.MethodsForty-two patients with chronic left ventricular dysfunction due to coronary artery disease underwent tagged and delayed enhanced magnetic resonance before and 10 ± 7 months after revascularization (coronary artery bypass graft: 35, percutaneous transluminal coronary angioplasty: 7). Left ventricular ejection fraction and regional mid-myocardial Eulerian radial thickening strain (Err) and mid-myocardial, subendocardial, and subepicardial Eulerian circumferential shortening strain (Ecc) strains were quantified in 16 segments per patient before and after revascularization and related to pre-operatively measured transmurality of necrosis.ResultsAt baseline, 256 of 672 segments were dysfunctional, having −10%) mid-myocardial Ecc. The magnitude of recovery of mid-myocardial Ecc (r = −0.33, p < 0.01) was inversely correlated with transmurality of necrosis before revascularization. Segments with

Urotensin II (UII) a potent vasoactive peptide is upregulated in the failing heart and promotes cardiomyocytes hypertrophy, in particular through mitogen-activated protein kinases. However, the regulation by UII of GSK-3beta, a recognized pivotal signaling element of cardiac hypertrophy has not yet been documented. We therefore investigated in adult cardiomyocytes, if UII phosphorylates GSK-3beta and Akt, one of its upstream regulators and stabilizes beta-catenin, a GSK-3beta dependent nuclear transcriptional co-activator. Primary cultures of adult rat cardiomyocytes were stimulated for 48h with UII. Cell size and protein/DNA contents were determined. Phosphorylated and total forms of Akt, GSK-3beta and the total amount of beta-catenin were quantified by western blot. The responses of cardiomyocytes to UII were also evaluated after pretreatment with the chemical phosphatidyl-inositol-3-kinase inhibitor, LY294002, and urantide, a competitive UII receptor antagonist. UII increased cell size and the protein/DNA ratio, consistent with a hypertrophic response. UII also increased phosphorylation of Akt and its downstream target GSK-3beta. beta-Catenin protein levels were increased. All of these effects of UII were prevented by LY294002, and urantide. The UII-induced adult cardiomyocytes hypertrophy involves the Akt/GSK-3beta signaling pathways and is accompanied by the stabilization of the beta-catenin. All these effects are abolished by competitive inhibition of the UII receptor, consistent with new therapeutic perspectives for heart failure treatment.

Background— Myocardial infarct scars are usually imaged by delayed-enhanced cardiac magnetic resonance (DE-cMR). In this study, we tested the hypothesis that the detection and quantification of myocardial scars can be evaluated by 3D echocardiography (3D-echo). Methods and Results— Fifty patients with a healed myocardial infarction (>3 months) and 10 controls underwent 3D echo and DE-cMR within 2 weeks. 3D-echo images were acquired with different settings, with or without contrast. The highest contrast-to-noise ratio was obtained with second-harmonic imaging (1.6/3.2 MHz), at a mechanical index of 0.5, in the presence of contrast. Using this modality, we calculated the sensitivity and specificity of the 3D-echo detection of cMR scars on a segmental basis to be 78% and 99%, respectively. On a per-patient basis, they were 96% and 90%, respectively. Good correlation and limits of agreement were found between the assessment of scar mass by 3D echo and DE-cMR ( r =0.93, P Conclusions— Contrast-enhanced 3D echo is a promising new tool for the detection and quantification of myocardial infarct scars.

A 78-year-old man at high risk for aortic valve replacement (Euroscore, 44%; left ventricular ejection fraction, 30%; previous bypass graft surgery) had undergone a transapical aortic valve implantation (26-mm Edwards Sapien) with a good immediate clinical and echocardiographic outcome: peak transvalvular gradient, 15 mm Hg; aortic valve area, 1.6 cm2; and trivial aortic regurgitation (Figure 1). He was treated with dual-antiplatelet therapy (clopidogrel, 75 mg/d for 1 month; aspirin, 100 mg/d lifelong), as recommended after Sapien valve implantation. The clinical and echocardiographic follow-ups at 1 month were excellent (New York Heart Association class II; peak transvalvular gradient, 18 mm Hg; aortic valve area, 1.6 cm2). Figure 1. Transoesophageal echocardiography images immediately after implantation of the Sapien valve. A, Low aortic transvalvular gradient; B, thin and normal leaflets; C, trivial aortic regurgitation. The patient was admitted 4 months after the procedure to the emergency department with a non–ST segment elevation myocardial infarction, signs of left heart failure, and an aortic systolic murmur. There was no evidence of endocarditis: no fever, no rash, and normal inflammatory parameters as per laboratory findings. The coronary angiogram showed graft patency, and the aortic angiogram (Figure 2) demonstrated …

Background Soluble suppression of tumorigenicity 2(sST2) receptor is a well-known biomarker implicated in inflammatory diseases. It has already been shown that sST2 is associated with worse outcome in HFrEF. Objective We sought to evaluate the association of sST2 with clinical, laboratory and imaging findings and its prognostic value in HFpEF. Methods Between January 2015 and June 2017, we prospectively enrolled 137 consecutive HFpEF patients (79 ± 8 years, 61% women). Elevated sST2 was determined by an age and sex-adjusted cutoff value (55 ng/ml) corresponding to mean + 2 SD in 31 controls (75 ± 6years, 61% women). All patients underwent complete 2D echo and cMR and were followed up for a composite outcome of mortality and first HF hospitalization. Results Median sST2 level was 44.5 ng/ml (IQR: 31.6–62.2 ng/ml). Elevated sST2 patients (n = 46) had an impaired right ventricular (RV) function (FAC 39 ± 10% vs. 43 ± 8%, P = 0.017; RVEF by cMR 53.5 ± 9.8% vs. 58.1 ± 7.8%, P = 0.008) and a higher proportion with pathologic RV/RA gradient (n = 20 (40%) vs. n = 23 (26%), P = 0.034). They were similar for other clinical, laboratory and imaging characteristics. Multivariate logistic analysis showed that only RVEF by cMR was associated with high sST2 level (OR: 0.94 [0.89–0.99], P = 0.010). During a mean follow-up of 20 ± 8months, 71 patients (52%) reached the combined end point. Cox analysis identified GFR, hemoglobin, sST2, use of loop diuretic and E/e’ ratio as significant predictors of outcome. Only GFR (HR = 0.98 [0.96–0.99], P Kaplan Meier event free survival curve showed that high sST2 HFpEF patients had poorer prognosis than low sST2 patients (P = 0.001, Fig. 1 ). Conclusions In HFpEF, sST2 is associated with impaired RV function and with a poorer prognosis with higher rate of mortality and first HF hospitalization.

Background Previous studies have shown that, in patients with severe aortic stenosis (SAS), global longitudinal strain (GLS), as assessed by speckle tracking echocardiography (STE), is often reduced. The present study aimed to understand the mechanisms underlying this reduction by using stress-shortening relationships. Method Ninety-nine patients with isolated SAS (36% men, 69 ± 11 years) and 75 healthy volunteers (HV) underwent resting 2D-echo and STE to measure GLS, global circumferential strain (GCS), rate-corrected mean velocity of fiber shortening (Vcfc), and end-systolic wall stress (ESWS). Stress-GLS, GCS or Vcfc relationships were constructed using the HV data and fitted to a linear regression. The relative position of individual SAS patients on these relationships was calculated and used as a load-independent index of myocardial contractility (unloaded GLS,GCS or Vcfc). At the time of surgery, myocardial biopsy was obtained to quantify interstitial fibrosis. Results GLS and Vcfc were lower in SAS than HV (−17 ± 3 vs. −20 ± 2%, P 5.4%), a real gradient is draw between the groups. The more fibrosis they have, the worse the longitudinal and circumferential functions are altered for a given afterload ( Fig. 1 ). Conclusion In HV, longitudinal function is less afterload-dependent than circumferential function. In SAS, reduced longitudinal or circumferential function is a marker of interstitial fibrosis and LV remodeling.

Recent studies showed that right ventricular systolic dysfunction (RVSD) predicts worse prognosis in patients with heart failure (HF). We thus sought to evaluate the prognostic value of RVSD assessed by cardiac magnetic resonance (CMR) in HF patients with low ejection fraction due to idiopathic (DCM

AIMS: The management of asymptomatic severe mitral regurgitation remains controversial. The aim of the study was to assess the long-term survival, incidence of cardiac complications, factors that predict outcome, and effect of mitral surgery on the long-term prognosis of patients with asymptomatic severe mitral regurgitation amenable to valve repair. METHODS: One hundred ninety-two asymptomatic patients (mean age 63 +/- 13 years) with severe degenerative mitral regurgitation diagnosed by 2-dimensional echocardiography between 1990 and 2001 were prospectively followed for a median of 8.5 years. RESULTS: Overall, cardiovascular, and event-free survival was evaluated in 2 groups of patients: a "conservative approach" group (n = 67) and an "early surgery" group (n = 125). Outcomes were also analyzed among patients with atrial fibrillation, pulmonary hypertension, or both, as well as in patients free of any mitral regurgitation complications. In the whole population, 10-year overall survival was significantly lower with the conservative approach than early surgery (50% +/- 7% vs 86% +/- 4%, log-rank < 0.0001). Similar results were obtained in the subgroups with atrial fibrillation and/or pulmonary hypertension. The 10-year propensity-matched score-adjusted hazards ratio for overall mortality, cardiac mortality, and cardiovascular events for the conservative treatment were 5.21, 4.83, and 4.40, respectively. CONCLUSION: Our results show that the outcome of asymptomatic patients with severe degenerative mitral regurgitation is better with an early surgical approach rather than a more conservative treatment strategy.

Objective: To assess the long-term survival, the incidence of cardiac complications and the factors that predict outcome in asymptomatic patients with severe degenerative mitral regurgitation (MR) undergoing mitral valve repair. Methods: Up to 143 asymptomatic patients (mean age 63+/-12 years) with severe degenerative MR who underwent mitral valve repair between 1990 and 2001 were subsequently followed up for a median of 8 years. The study population was subdivided into three subgroups: patients with left ventricular (LV) dysfunction and/or dilatation (n=18), patients with atrial fibrillation and/or pulmonary hypertension (n=44) and patients without MR-related complications (n=81). Results: For the patients, 10-year overall and cardiovascular survival was 82+/-4% and 90+/-3%. At 10 years, patients without preoperative MR-related complications had significantly better overall survival than patients with preoperative LV dysfunction and/or dilatation (89+/-4% vs 57+/-13%, log rank p=0.001). Patients without preoperative MR-related complications also tended to have a better 10-year overall and cardiovascular survival than patients with atrial fibrillation and/or pulmonary hypertension (overall survival of 79+/-8%), although this did not reach statistical significance (log rank p=0.17). Cox regression analysis identified the baseline left ventricular ejection fraction and age as the sole independent predictors of outcome. Conclusion: Our data indicate that in asymptomatic patients with severe degenerative MR, mitral valve repair is associated with an excellent long-term prognosis. Nonetheless, the presence of preoperative MR-related complications, in particular LV dysfunction and/or dilatation, greatly attenuates the benefits of surgery. This suggests that mitral valve repair should be performed early, before any MR-related complications ensue.

OBJECTIVES: The aim of the present study was to examine the intraoperative echocardiographic features associated with recurrent severe aortic regurgitation (AR) after an aortic valve repair surgery. BACKGROUND: Surgical valve repair for AR has significant advantages over valve replacement, but little is known about the predictors and mechanisms of its failure. METHODS: We blindly reviewed all clinical, pre-operative, intraoperative, and follow-up transesophageal echocardiographic data of 186 consecutive patients who underwent valve repair for AR during a 10-year period and in whom intraoperative and follow-up echo data were available. After a median follow-up duration of 18 months, 41 patients had recurrent 3+ AR, 23 patients presented with residual 1+ to 2+ AR, and 122 had no or trivial AR. In patients with recurrent 3+ AR, the cause of recurrent AR was the rupture of a pericardial patch in 3 patients, a residual cusp prolapse in 26 patients, a restrictive cusp motion in 9 patients, an aortic dissection in 2 patients, and an infective endocarditis in 1 patient. RESULTS: Pre-operatively, all 3 groups were similar for aortic root dimensions and prevalence of bicuspid valve (overall 37%). Patients with recurrent AR were more likely to display Marfan syndrome or type 3 dysfunction pre-operatively. At the opposite end, patients with continent AR repair at follow-up were more likely to have type 2 dysfunction pre-operatively. After cardiopulmonary bypass, a shorter coaptation length, the degree of cusp billowing, a lower level of coaptation (relative to the annulus), a larger diameter of the aortic annulus and the sino-tubular junction, the presence of a residual AR, and the width of its vena contracta were associated with the presence of AR at follow-up. Multivariate Cox analysis identified a shorter coaptation length (odds ratio [OR]: 0.8, p = 0.05), a coaptation occurring below the level of the aortic annulus (OR: 7.9, p < 0.01), a larger aortic annulus (OR: 1.2, p = 0.01), and residual aortic regurgitation (OR: 5.3, p = 0.01) as risk factors of repair failure. CONCLUSIONS: Our results demonstrate that intraoperative transesophageal echocardiography can be used to identify patients undergoing AR repair who are at increased risk for late repair failure.

BACKGROUND: Cusp prolapse management is important in aortic valve (AV) sparing and repair to achieve durable results. We analyzed the midterm outcomes of two different techniques for trileaflet AV prolapse repair. METHODS: Between 1996 and 2008, 376 patients underwent elective AV repair: 88 with trileaflet AV (23%) had cusp prolapse repair, plication technique was performed in 34 (39%), resuspension technique in 33 (37%) and plication plus resuspension in 21 (24%). One cusp was repaired in 55 (62%), 2 cusps in 18 (21%), and 3 cusps in 15 (17%). RESULTS: No hospital deaths occurred. Patients undergoing resuspension with or without plication had more preoperative aortic insufficiency (AI; p = 0.01) and multiple cusp prolapses (p = 0.01). During follow-up (median, 41 months), 4 deaths occurred and 2 were cardiac related. Overall survival at 5 years was 95% +/- 5%. Two patients needed AV reoperation because of recurrent AI or AI plus AV stenosis. Recurrent AI grade > or =3+ developed in 4 patients; 1 with moderate AV stenosis. Freedom from reoperation at 5 years was 100% for plication, 96% +/- 4% for resuspension, and 93% +/- 7% for plication plus resuspension (p = 0.6); respective freedom from AI > or =3+ at 3 years was 100%, 92% +/- 8%, and 89% +/- 11% (p = 0.8). CONCLUSIONS: Cusp plication or resuspension are efficient and durable techniques to correct cusp prolapse in the trileaflet AV. Plication is typically the first choice because of its ease of use and lower risk of overcorrection; however, free margin resuspension is useful in specific situations.

BACKGROUND: Repair of rheumatic mitral valves has met with limited success because hemodynamic obstruction may persist after repair because of residual diseased leaflet tissue and lack of suppleness. Over the past decade, we have developed and implemented an aggressive approach to rheumatic mitral valve repair with radical excision of the diseased leaflets area, and subvalvular apparatus and subsequent reconstruction, with the objective of removing all diseased valvular tissue. METHODS: From July 1996 to June 2007, 78 patients underwent mitral valve repair for rheumatic valve disease. Over the same time interval, 54 patients underwent mitral valve replacement. Mean age was 56.4 +/- 16 years. Clinical follow-up (mean 60 +/- 36 months) was complete in 100% of patients, and echocardiographic follow-up (mean 52 +/- 37 months) was 96% complete. RESULTS: There was no hospital mortality or early reoperations. Overall survival was 94% +/- 6% at 8 years, and 95% of patients were in New York Heart Association functional class II or less. Three patients (4%) required reoperation for mitral restenosis and 2 underwent re-repair. At 8 years of follow-up, freedom from cardiac death and mitral valve reoperation were 98% +/- 2% and 94% +/- 5%, respectively. Freedom from valve-related events at 5 and 10 years was 90% +/- 8% and 86% +/- 11%, and freedom from significant mitral regurgitation was 98% +/- 2% at 5 years and 83% +/- 9% at 8 years. CONCLUSIONS: A more aggressive approach to resection of diseased valvular tissue with subsequent reconstruction is feasible, with good midterm results, and may extend the scope of valve repair in rheumatic disease patients.

Ultrasound-targeted microbubble destruction (UTMD) can cause left ventricular (LV) dysfunction and tissue alterations in rats when high ultrasound (US) energy and long duration of imaging are used. However, the mechanism underlying these alterations remains unclear. The aim of the present work was to investigate the possible role of ischemia in the pathogenesis of the UTMD-induced LV damages in rats. To address this issue, rat hearts were exposed in situ to perfluorocarbon-enhanced sonicated dextrose albumin (PESDA) and US at peak negative pressures of 0.6, 1.2 or 1.8 MPa for 1, 3, 9, 15 or 30 min. Blood pressure and electrocardiogram were continuously recorded during insonation. LV function was assessed before and immediately after US exposure, as well as at 24 h and 7 d. At each time point, groups of rats were euthanized and their hearts were harvested for morphologic analysis. Rats exposed to either PESDA alone or US alone showed no functional or morphologic abnormalities. By contrast, rats exposed to both PESDA and US exhibited transient LV dysfunction, transient ST-segment elevation, premature ventricular contractions, microvascular ruptures, contraction band necrosis and morphologic tissue damage. These bio-effects were spontaneously and completely reversible by one week, except in the groups exposed to the highest peak negative pressure for the longest duration, in which mild dysfunction persisted and interstitial fibrosis developed. In conclusion, simultaneous exposure of rat hearts to PESDA and US in vivo results in significant bio-effects that are similar to myocardial ischemia, including transient regional LV dysfunction, transient ST-segment elevation and myocyte contraction band necrosis. (E-mail: vanoverschelde@card.ucl.ac.be).

Aims The aim of this article is to evaluate the accuracy and reproducibility of two-dimesional speckle tracking echocardiography (2D-STE) for the estimation of left ventricular (LV) twist, using tagged cardiac magnetic resonance (cMR) as the reference standard, and to assess how much 2D-STE rotational parameters are affected by the level at which measurements are made within the LV. Methods and results Forty-three patients with various heart diseases and 10 healthy volunteers underwent cMR and 2D-STE on the same day. With both methods, basal and apical time-rotation curves were generated at endocardial, midwall, and epicardial levels. By using the most apical cMR short-axis cross-section as a comparator, apical rotation was significantly underestimated by 2D-STE. When 2D-STE and cMR short-axis cross-sections were matched for their internal dimensions, measurements of endocardial, midwall, and epicardial twists no longer differ between cMR and 2D-STE (12.6 +/- 5.9 vs. 12.5 +/- 5.7 degrees , 10.5 +/- 4.6 vs. 9.7 +/- 4.1 degrees , and 8.9 +/- 4.0 vs. 8.4 +/- 3.7 degrees , respectively, all P = ns). Conclusion Compared with tagged cMR, 2D-STE underestimates apical rotation and LV twist. This is related to the inability of 2D-STE to image the real LV apex in most of the patients. However, when 2D-STE and cMR data are compared at similar acquisition levels, both techniques provide similar values.

Chronic ischemic left ventricular dysfunction is present in a number of clinical syndromes in which myocardial revascularization results in an improvement of left ventricular function, patients' functional class, and their survival. Early diagnosis of and treatment of viability is essential. Coronary arteriography is of limited value in diagnosis of viability. Noninvasive testing is essential for diagnosis, which can be matched to the pathophysiologic changes that occur in hibernating myocardium. However, no single test has a perfect, or near perfect, sensitivity and specificity, and thus, a combination of tests are usually needed. Algorithms are developed to integrate these tests in clinical decision making.

Besides its usefulness for the detection of exercise-induced ischemia, conventional exercise testing may help to predict the onset of clinical events and the need for surgery in asymptomatic patients with cardiac-valvular disease. Doppler echocardiography examination during exercise recently emerged as a new stress testing modality that may add useful information regarding dynamism of LV function, valve disease severity and pulmonary circulation. Few studies have demonstrated a correlation between the results of exercise Doppler echocardiography and clinical outcome. Preliminary experience needs to be confirmed to warrant routine use of Doppler echocardiography examination during exercise in the evaluation of patients with cardiac-valve disease. (C) 2008 Elsevier Masson SAS. All rights reserved.

BACKGROUND: We examined flow-function relationships in humans with chronic coronary artery disease (CAD) in relation to the transmural extent of necrosis, aiming to distinguish the various pathophysiologic conditions that cause chronic ischemic dysfunction, ie, chronic hibernation (perfusion-contraction match) from chronic stunning (perfusion-contraction mismatch). METHODS AND RESULTS: Twenty-two patients (18 men, 61 +/- 13 years) with CAD and chronic contractile dysfunction (ejection fraction, 26% +/- 13%) and 6 volunteers underwent tagged and gadolinium (Gd)-DTPA contrast-enhanced magnetic resonance imaging as well as (13)NH(3)-positron emission tomography. The relationship between regional circumferential shortening strain (ECC), transmural necrosis, and absolute transmural myocardial perfusion (MBF) was examined quantitatively in dysfunctional segments (

The main role of insulin in the heart under physiological conditions is obviously the regulation of substrate utilization. Indeed, insulin promotes glucose uptake and its utilization via glycolysis. In addition, insulin participates in the regulation of long-chain fatty acid uptake, protein synthesis, and vascular tonicity. Significant advancements have been made over the last 20 years in the understanding of the signal transduction elements involved in these insulin effects. Among these molecular mechanisms, the phosphatidylinositol 3-kinase/protein kinase B (Akt) pathway is thought to play a crucial role. Under pathological conditions, such as type-2 diabetes, myocardial ischaemia, and cardiac hypertrophy, insulin signal transduction pathways and action are clearly modified. These molecular signalling alterations are often linked to atypical crosstalks with other signal transduction pathways. On the other hand, pharmacological modifications of parallel and interdependent signalling components, such as the AMP-activated protein kinase pathway, are now considered to be a good therapeutic approach to treat insulin-signalling defects such as insulin resistance and type-2 diabetes. In this review, we will focus on the description of the molecular signalling elements involved in insulin action in the heart and vasculature under these different physiological, pathological, and therapeutical conditions.

Aim: To evaluate if three-dimensional echocardiography (3-DE) is as accurate and reproducible as cine magnetic resonance imaging (cMR) in estimating left ventricular (LV) parameters in patients with and without wall motion abnormalities (WMA). Methods: 83 patients (33 with WMA) underwent 3-DE and cMR. 3-DE datasets were analysed using a semi-automatic contour detection algorithm. The accuracy of 3-DE was tested against cMR in the two groups of patients. All measurements were made twice by two different observers. Results: LV mass by 3-DE was similar to that obtained by cMR (149 (SD 42) g vs 148 (45) g, p = 0.67), with small bias (1 (28) g) and excellent interobserver agreement (−2 (31) g vs 4 (26) g). The two measurements were also highly correlated (r = 0.94), irrespective of WMA. End-diastolic and end-systolic LV volumes and ejection fraction by 3-DE and cMR were highly correlated (r = 0.97, 0.98, 0.94, respectively). Yet, 3-DE underestimated cMR end-diastolic volumes (167 (68) ml vs 187 (70) ml, p

BACKGROUND: Recent experimental data have shown that the combined exposure of rodent hearts to high acoustic pressure and ultrasound contrast agents can induce vascular injury and cell damage. The aim of the present work was to test whether similar effects can be observed in humans. METHODS AND RESULTS: Twenty patients underwent simultaneous arterial and coronary sinus blood sampling during contrast-enhanced echocardiography using Perfluorocarbon-enhanced Sonicated Dextrose Albumin. Control subjects were compared to groups of patients exposed to either high mechanical index (MI = 1.5) triggered second harmonic (1.3-2.6 MHz) imaging or low mechanical index (MI = 0.2) real-time power modulation imaging for 15 min. No significant changes arterio-venous differences in lactate, total creatine kinase (CK) and myoglobin occurred over time in the three groups. Similarly, the arterio-venous difference in CK-MB and troponin I remained stable over time in control and low-MI patients. By contrast, these two parameters progressively increased over time in the high-MI group (P < 0.05 vs. baseline and vs. controls). CONCLUSION: Our data suggest that high-MI contrast-enhanced echocardiography can cause subclinical release of cardiac bio-markers in humans, while low-MI real-time imaging appears to be safer.

PURPOSE: To compare the accuracy of planimetric and continuity equation measurements of aortic valve area (AVA) by cardiac MR (cMR) to each other and against transthoracic (TTE) and transesophageal (TEE) echocardiography. MATERIALS AND METHODS: A total of 31 patients (21 men, mean age = 67 +/- 13 years) with aortic stenosis (AS) and 16 controls (12 men, mean age = 57 +/- 14 years) underwent measurement of AVA by planimetric and continuity equation cMR. Measurements were compared to TEE planimetry and continuity equation TTE. RESULTS: AVA by continuity equation cMR correlated highly to continuity equation TTE (r = 0.98) and was not significantly different (1.8 +/- 1.3 cm2 vs. 1.8 +/- 1.4 cm2, P = 0.62). Similarly, AVA by cMR planimetry was not statistically different from TEE planimetry (2.1 +/- 1.7 cm2 vs. 2.1 +/- 1.6 cm2, P = 0.34) and correlated highly (r = 0.98). Yet planimetric measurements of AVA by cMR and TEE were significantly higher than AVA by continuity equation cMR (P < 0.001 and P < 0.001, respectively) and TTE (P < 0.001 and P < 0.001, respectively). CONCLUSION: Both planimetry and continuity equation-based measurements of AVA by cMR are equally accurate. However, similar to TEE, cMR AVA is larger by planimetry than by continuity equation. This is consistent with the contention that the anatomical maximum opening of a stenotic aortic valve is larger than the size of the functional vena contracta.

OBJECTIVES Cardiac transplantation using hearts from donors after circulatory death (DCD) is critically limited by the unavoidable warm ischaemia and its related unpredictable graft function. Inasmuch as hypothermic machine perfusion (MP) has been shown to improve heart preservation, we hypothesized that MP could enable the use of DCD hearts for transplantation. METHODS We recovered 16 pig hearts following anoxia-induced cardiac arrest and cardioplegia. Grafts were randomly assigned to two different groups of 4-h preservation using either static cold storage (CS) or MP (Modified LifePort© System, Organ Recovery Systems©, Itasca, Il). After preservation, the grafts were reperfused ex vivo using the Langendorff method for 60 min. Energetic charge was quantified at baseline, post-preservation and post-reperfusion by measuring lactate and high-energy phosphate levels. Left ventricular contractility parameters were assessed both in vivo prior to ischaemia and ex vivo during reperfusion. RESULTS Following preservation, the hearts that were preserved using CS exhibited higher lactate levels (57.1 ± 23.7 vs 21.4 ± 12.2 µmol/g; P < 0.001), increased adenosine monophosphate/adenosine triphosphate ratio (0.53 ± 0.25 vs 0.11 ± 0.11; P < 0.001) and lower phosphocreatine/creatine ratio (9.7 ± 5.3 vs 25.2 ± 11; P < 0.001) in comparison with the MP hearts. Coronary flow was similar in both groups during reperfusion (107 ± 9 vs 125 ± 9 ml/100 g/min heart; P = ns). Contractility decreased in the CS group, yet remained well preserved in the MP group. CONCLUSION MP preservation of DCD hearts results in improved preservation of the energy and improved functional recovery of heart grafts compared with CS.

BACKGROUND: Gadolinium (Gd) Extracellular volume fraction (ECV) by Cardiovascular Magnetic Resonance (CMR) has been proposed as a non-invasive method for assessment of diffuse myocardial fibrosis. Yet only few studies used 3 T CMR to measure ECV, and the accuracy of ECV measurements at 3 T has not been established. Therefore the aims of the present study were to validate measurement of ECV by MOLLI T1 mapping by 3 T CMR against fibrosis measured by histopathology. We also evaluated the recently proposed hypothesis that native-T1 mapping without contrast injection would be sufficient to detect fibrosis. METHODS: 31 patients (age = 58 ± 17 years, 77% men) with either severe aortic stenosis (n = 12) severe aortic regurgitation (n = 9) or severe mitral regurgitation (n = 10), all free of coronary artery disease, underwent 3 T-CMR with late gadolinium enhancement (LGE) and pre- and post-contrast MOLLI T1 mapping and ECV computation, prior to valve surgery. LV biopsies were performed at the time of surgery, a median 13 [1-30] days later, and stained with picrosirius red. Pre-, and post-contrast T1 values, ECV, and amount of LGE were compared against magnitude of fibrosis by histopathology by Pearson correlation coefficients. RESULTS: The average amount of interstitial fibrosis by picrosirius red staining in biopsy samples was 6.1 ± 4.3%. ECV computed from pre-post contrast MOLLI T1 time changes was 28.9 ± 5.5%, and correlated (r = 0.78, p

Conflicting evidence exists about the value of general practitioners' (GPs') diagnoses of chronic heart failure (CHF), especially in older persons. Therefore, the relationship between GPs' judgement of CHF and objective cardiac abnormalities and their respective prognostic value for 5-year mortality in patients aged 80 and older was studied.These analyses were embedded within the prospective, population-based BELFRAIL study. At baseline, 525 patients (mean age 85 ± 3.7 years, 37% men) were clinically assessed by their GPs, had NT-proBNP levels determined and received a detailed echocardiography at home. GPs were asked to judge the presence of CHF and to list their arguments in favour or against CHF. Cause-specific mortality was collected until 5.2 ± 0.25 years after baseline. GPs suspected CHF in 154 patients (29%). The prevalence of objective cardiac abnormalities was 35% (n=183). GPs' judgement predicted objective cardiac abnormalities inaccurately (sensitivity 45% (95% CI 38-53), specificity 79% (95% CI 75-83)). However, both objective cardiac abnormalities and GPs' diagnoses of CHF were good predictors of 5-year mortality (HR 2.1 (95% CI 1.6-2.7) vs 1.7 (95% CI 1.3-2.3), respectively). Furthermore, the presence of objective cardiac abnormalities was not significantly better than GPs' judgement in identifying patients at risk for mortality, although a trend for better cardiovascular mortality risk classification was noted (NRI 10% (95% CI -2 to 21%), P=0.13).Although GPs' judgement of CHF and objective cardiac abnormalities correlated poorly, the validity of GPs' clinical judgement for mortality risk stratification was demonstrated.

Background Paradoxical low gradient (PLG) severe aortic stenosis (SAS) is a recently described subset of SAS, which is a matter of intense debate. Some authors indeed consider this new entity as a more advanced form of SAS, whereas others believe the opposite. To get further insight into the pathophysiology of PLG SAS, we compared the weight of the valves explanted at the time of surgery (AVR) and the degree of valve calcification among consecutive patients with PLG SAS and high-gradient (HG) SAS. Methods We prospectively recruited 38 consecutive patients (20 men; mean age: 73 yrs) with isolated non-rheumatic SAS (indexed aortic valve area (AVAi) Results PLG and HG SAS had similar baseline characteristics with the exception of AVAi which was higher (0.44±0.06 vs 0.36±0.10 cm2m2, p=0.008) and MG which was lower (32±7 vs 55±12 mmHg, p 0.90) and in-vivo (r2=0.71) Agatston scores. Interestingly, valves explanted from patients with PLG SAS were lighter (1.58±0.65 vs 2.65±1,24g, p=0.001) and showed lower ex-vivo Agatston scores (363±282 vs 1211±840, p Conclusion The valves weight and degree of valve calcification reported in our study indicate that PLG SAS valves are less severely affected than HG SAS valves. These data thus reinforce the hypothesis that PLG SAS is a lesser advanced form of aortic stenosis than HG SAS.

BackgroundDespite the absence of randomized studies comparing mitral valve (MV) repair and replacement, international guidelines strongly recommend MV repair as the optimal surgical treatment for severe degenerative mitral regurgitation (dMR). Yet, the level of evidence supporting these recommendations is low, owing to the lack of available clinical trial data. In this context, analysis of large multicenter registries becomes critical.ObjectiveTo compare very long-term survival among patients (pts) undergoing MV repair versus replacement for the treatment of severe dMR using the technique of propensity score (PS) matching to reduce bias in nonrandomized cohorts.MethodsThe Mitral Regurgitation International DAtabase (MIDA) is a prospective multicenter registry that includes 2,569 consecutive pts with dMR, who were recruited in 6 tertiary centers (France, Italy, Belgium, and the United States) between 1980 and 2005. Among these, we identified 1,922 pts who underwent mitral surgery, including 1,709MV repairs and 213MV replacements. We compared operative mortality and overall survival in both the entire study population and in 615 PS-matched (2:1) pts.ResultsOperative mortality was lower after MV repair than after MV replacement, both in the entire population (2 vs 7%; p=0.001) and in the PSmatched pts (4 vs 8%; p=0.04). Similarly, 20-year survival was better after MV repair than after MV replacement, both in the entire population (46% [(95% CI, 39%-52%] vs 23% [95% CI, 14%-32%], p