Postconditioning attenuates no-reflow in STEMI patients.

After acute myocardial infarction, the presence of no-reflow (or microvascular obstruction: MVO) has been associated with adverse left ventricular (LV) remodeling and worse clinical outcome. This study examined the effects of mechanical ischemic postconditioning on early and late MVO size in acute ST-elevation myocardial infarction (STEMI) patients. Fifty patients undergoing primary coronary angioplasty for a first STEMI with TIMI grade flow 0-1 and no collaterals were randomized to ischemic postconditioning (PC) (n = 25) or control (n = 25) groups. Ischemic PC consisted in the application of four consecutive cycles of a 1-min balloon occlusion, each followed by a 1-min deflation at the onset of reperfusion. Early (3 min post-contrast) and late (10 min post-contrast) MVO size were assessed by contrast-enhanced cardiac-MRI within 96 h after reperfusion. PC was associated with smaller early and late MVO size (3.9 ± 4.8 in PC versus 7.8 ± 6.6% of LV in controls for early MVO, P = 0.02; and 1.8 ± 3.1 in PC versus 4.1 ± 3.9% of LV in controls for late MVO; P = 0.01). This significant reduction was persistent after adjustment for thrombus aspiration, which neither had any significant effect on infarct size, nor on early or late MVO (P = NS for all). Attenuation of MVO was associated to infarct size reduction. Mechanical postconditioning significantly reduces MVO in patients with acute STEMI treated with primary angioplasty.

Isolated functional tricuspid regurgitation: how to define patients at risk for event?

AIMS: Functional tricuspid regurgitation (TR) is a turning point in cardiac diseases. Symptoms typically appear late. The optimal timing for proposing a valve repair remains a challenge. We sought to analyse the characteristics of right heart remodelling in patients with significant functional TR to identify the parameters that could be used in a simple prognostic model predicting clinical events. METHODS AND RESULTS: We designed a prospective observational French multicentre study including 160 patients with significant functional TR (effective regurgitant orifice area > 30 mm2 ) and left ventricular ejection fraction > 40%. Clinical, echocardiographic, and electrocardiogram data were collected at baseline and at the 1 and 2 year follow-up. The primary outcome was all-cause death or hospitalization for heart failure. At 2 years, 56 patients (35%) achieved the primary outcome. The subset with events showed more advanced right heart remodelling at baseline, but similar TR severity. Right atrial volume index (RAVI) and the tricuspid annular plane systolic excursion to systolic pulmonary arterial pressure (TAPSE/sPAP) ratio, reflecting right ventricular-pulmonary arterial coupling, were 73 mL/m2 and 0.40 vs. 64.7 mL/m2 and 0.50 in the event vs. event-free groups, respectively (both P < 0.05). None among all the clinical and imaging parameters tested had a significant group × time interaction. The multivariable analysis leads to a model including TAPSE/sPAP ratio > 0.4 (odds ratio = 0.41, 95% confidence limit 0.2 to 0.82) and RAVI > 60 mL/m2 (odds ratio = 2.13, 95% confidence limit 0.96 to 4.75), providing a clinically valid prognostic evaluation. CONCLUSIONS: RAVI and TAPSE/sPAP are relevant for predicting the risk for event at 2 year follow-up in patients with an isolated functional TR.

What underlies sex differences in heart failure onset within the first year after a first myocardial infarction?

Background: Women are more likely to develop heart failure (HF) after myocardial infarction. However, diagnosis and reperfusion are often delayed. Objectives: To compare the prevalence of HF after primary percutaneous coronary intervention (PPCI)-treated ST segment myocardial infarction (STEMI) between sexes and to study its associations with comorbidities, infarct size, and left ventricular (LV) systolic and diastolic dysfunctions (DD). Methods: The patients with PPCI-treated anterior STEMI, from the CIRCUS study cohort, were followed up for 1 year and HF events were recorded. Evaluation of ejection fraction (LVEF) and DD were performed at baseline and at 1 year. The elevated LV filling pressure (LVFP) included Grades 2 and 3 DD. Results: Of the 791 patients from the CIRCUS study, 135 were women. At 1 year, the proportion of patients who developed HF was 21% among men and 34% among women (p = 0.001). In the subset of 407 patients with available diastolic parameters, the rate of HF was also higher in women. HF during the initial hospitalization was comparable between the sexes. However, women had a higher incidence of rehospitalization for HF within the first year after STEMI (14.1% vs. 4.1%, p = 0.005). Women were older with a higher prevalence of hypertension. The infarct size and LVEF were similar between the sexes. Elevated LVFP was observed more frequently in women than in men during the initial hospitalization and at 1 year (26% vs. 12%, p = 0.04, and 22% vs. 12%, p = 0.006, respectively). Interestingly, only initial elevated LVFP (HR 5.9, 95% CI: 2.4-14.5, p < 0.001), age, and hypertension were independently associated with rehospitalization for HF. Conclusions: After PPCI-treated anterior STEMI, despite comparable infarct size and LVEF, women presented a higher proportion of rehospitalization for HF than men. That was likely due to a greater DD associated with older age and hypertension.

Intracoronary autologous mononucleated bone marrow cell infusion for acute myocardial infarction: results of the randomized multicenter BONAMI trial.

AIMS: Intracoronary administration of autologous bone marrow cells (BMCs) leads to a modest improvement in cardiac function, but the effect on myocardial viability is unknown. The aim of this randomized multicentre study was to evaluate the effect of BMC therapy on myocardial viability in patients with decreased left ventricular ejection fraction (LVEF) after acute myocardial infarction (AMI) and to identify predictive factors for improvement of myocardial viability. METHODS AND RESULTS: One hundred and one patients with AMI and successful reperfusion, LVEF ≤45%, and decreased myocardial viability (resting Tl201-SPECT) were randomized to either a control group (n = 49) or a BMC group (n = 52). Primary endpoint was improvement of myocardial viability 3 months after AMI. Baseline mean LVEF measured by radionuclide angiography was 36.3 ± 6.9%. Bone marrow cell infusion was performed 9.3 ± 1.7 days after AMI. Myocardial viability improved in 16/47 (34%) patients in the BMC group compared with 7/43 (16%) in the control group (P = 0.06). The number of non-viable segments becoming viable was 0.8 ± 1.1 in the control group and 1.2 ± 1.5 in the BMC group (P = 0.13). Multivariate analysis including major post-AMI prognostic factors showed a significant improvement of myocardial viability in BMC vs. control group (P = 0.03). Moreover, a significant adverse role for active smoking (P = 0.04) and a positive trend for microvascular obstruction (P = 0.07) were observed. CONCLUSION: Intracoronary autologous BMC administration to patients with decreased LVEF after AMI was associated with improvement of myocardial viability in multivariate-but not in univariate-analysis. A large multicentre international trial is warranted to further document the efficacy of cardiac cell therapy and better define a group of patients that will benefit from this therapy. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier NCT00200707.

Functional tricuspid regurgitation: A clustering analysis and prognostic validation of three echocardiographic phenotypes in an external cohort.

BACKGROUND: Functional tricuspid regurgitation (FTR) is an independent risk factor for morbidity and mortality. New pathophysiological concepts but also new therapeutic options are justifying new knowledges for characterizing FTRs and their prognoses. AIM: To study echocardiographic criteria associated with prognosis in FTR-patients using a clustering method in two cohorts. METHODS AND RESULTS: Two hundred forty-one patients with at least severe (≥grade 3) TR were enrolled: 92 in the retrospective cohort (mean age 77.9 ± 13 years) and 149 in the prospective validation cohort. Hierarchical clustering analysis was conducted. Four parameters explained the clustering categorization according to a multinomial regression (right ventricular (RV) end-diastolic mid-cavity diameter, RV free-wall strain, right atrial (RA) volume index, RA strain; p = 0.0039). Three clusters were identified in the retrospective cohort: Cluster 1 had better right ventricular, left ventricular, and right atrial function than Cluster 2 (reduced RV and RA strain despite similar sizes). Cluster 3 included patients with severely dilated heart chambers associated to RV and RA dysfunctions. When applying the model in the validation (external) cohort, the rate of the primary endpoint (hospitalization for heart failure and/or death from any cause) was lowest in Cluster 1 (30.8% versus 48% and 58.8% in Clusters 2 and 3, respectively; p < 0.05). CONCLUSION: In FTR patients, different profiles of RV and RA remodeling are associated with different outcomes. Therefore, the diagnostic work-up in this clinical setting should include RV and RA characteristics. Under noninterventional management, the phenotype corresponding to preserved RV size and preserved RA and RV functions appears to have a better prognosis.

Multicentric randomized evaluation of a tricuspid valve percutaneous repair system (clip for the tricuspid valve) in the treatment of severe secondary tricuspid regurgitation Tri.Fr Design paper.

AIMS: Tricuspid regurgitation (TR) is associated with significant morbidity and mortality. Its independent prognostic role has been repeatedly demonstrated. However, this valvular heart condition is largely undertreated because of the increased risk of surgical repair. Recently, transcatheter techniques for the treatment of TR have emerged, but their implications for the clinical endpoints are still unknown. METHODS AND RESULTS: The Tri.fr trial will be a multicentre, controlled, randomized (1:1 ratio), superior, open-label, and parallel-group study conducted in 300 patients with severe secondary TR that is considered non-surgical by heart teams. Inclusion will be possible only after core laboratory review of transthoracic and transoesophageal echocardiography and after validation by the clinical eligibility committee. A description of the mechanisms of the TR will be conducted by the core laboratory. Atrial or ventricular impacts on the severity of the secondary TR will be taken into account for the randomization. The patients will be followed for 12-month, and the primary outcome will be the Packer composite clinical endpoint [combining New York Heart Association class, patient global assessment (PGA), and major cardiovascular events]. It will test the hypothesis that a tricuspid valve percutaneous repair strategy using a clip dedicated to the tricuspid valve is superior to best guideline-directed medical therapy in symptomatic patients with severe secondary TR. CONCLUSION: Tri.fr will be the first randomized, academic, multicentre study testing the value of percutaneous correction in patients with severe secondary TR.

Effect of cyclosporine on reperfusion injury in acute myocardial infarction.

BACKGROUND: Experimental evidence suggests that cyclosporine, which inhibits the opening of mitochondrial permeability-transition pores, attenuates lethal myocardial injury that occurs at the time of reperfusion. In this pilot trial, we sought to determine whether the administration of cyclosporine at the time of percutaneous coronary intervention (PCI) would limit the size of the infarct during acute myocardial infarction. METHODS: We randomly assigned 58 patients who presented with acute ST-elevation myocardial infarction to receive either an intravenous bolus of 2.5 mg of cyclosporine per kilogram of body weight (cyclosporine group) or normal saline (control group) immediately before undergoing PCI. Infarct size was assessed in all patients by measuring the release of creatine kinase and troponin I and in a subgroup of 27 patients by performing magnetic resonance imaging (MRI) on day 5 after infarction. RESULTS: The cyclosporine and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before PCI. The release of creatine kinase was significantly reduced in the cyclosporine group as compared with the control group (P=0.04). The release of troponin I was not significantly reduced (P=0.15). On day 5, the absolute mass of the area of hyperenhancement (i.e., infarcted tissue) on MRI was significantly reduced in the cyclosporine group as compared with the control group, with a median of 37 g (interquartile range, 21 to 51) versus 46 g (interquartile range, 20 to 65; P=0.04). No adverse effects of cyclosporine administration were detected. CONCLUSIONS: In our small, pilot trial, administration of cyclosporine at the time of reperfusion was associated with a smaller infarct by some measures than that seen with placebo. These data are preliminary and require confirmation in a larger clinical trial.

Cardiac remodelling in secondary tricuspid regurgitation: Should we look beyond the tricuspid annulus diameter?

BACKGROUND: A better understanding of the mechanism of tricuspid regurgitation severity would help to improve the management of this disease. AIM: We sought to characterize the determinants of isolated secondary tricuspid regurgitation severity in patients with preserved left ventricular ejection fraction. METHODS: This was a prospective observational multicentre study. Patients with severe tricuspid regurgitation were asked to participate in a registry that required a control echocardiogram after optimization of medical treatment and a follow-up. Patients had to have at least mild secondary tricuspid regurgitation when clinically stable, and were classified according to five grades of tricuspid regurgitation severity, based on effective regurgitant orifice area. RESULTS: One hundred patients with tricuspid regurgitation (12 mild, 31 moderate, 18 severe, 17 massive and 22 torrential) were enrolled. Right atrial indexed volume and tethering area were statistically associated with the degree of tricuspid regurgitation (P<0.001 and P=0.005, respectively). When the tricuspid annular diameter was≥50mm, the probability of having severe tricuspid regurgitation or a higher grade was>70%. For an increase of 10mL/m2 in right atrial volume, the effective regurgitant orifice area increased by 4.2mm2, and for an increase of 0.1cm2 in the tethering area, the effective regurgitant orifice area increased by 2.35mm2. The degree of right ventricular dilation and changes in tricuspid morphology were significantly related to tricuspid regurgitation severity class (P<0.001). No significant difference in right ventricular function variables was observed between the tricuspid regurgitation classes. CONCLUSIONS: For tricuspid regurgitation to be severe or torrential, both right atrial dilatation and leaflet tethering are needed. Interestingly, right cavities dilated progressively with tricuspid regurgitation severity, without joint degradation of right ventricular systolic function variables.

Rational and design of the ROTAS study: a randomized study for the optimal treatment of symptomatic patients with low-gradient severe aortic valve stenosis and preserved left ventricular ejection fraction.

AIMS: Fifteen to thirty percentage of patients with severe aortic stenosis (AS) have preserved left ventricular ejection fraction (LVEF) and a discordant AS pattern at Doppler echocardiography, which is characterized by a small (<1 cm2) aortic area and low mean aortic gradient (<40 mmHg). The 'Randomized study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic Stenosis and preserved left ventricular ejection fraction' (ROTAS trial) aims at demonstrating the superiority of aortic valve replacement vs. a 'watchful waiting strategy' in symptomatic patients with low-gradient (LS), severe AS, and preserved LVEF, stratified according to indexed stroke volume, in terms of all-cause mortality or cardiovascular-related hospitalization during follow-up (FU). METHODS AND RESULTS: The ROTAS trial will be a multicentre randomized non-blinded study involving 16 reference centres. AS severity will be confirmed by a multimodality approach (rest and stress echocardiography, calcium scoring, and cardiac magnetic resonance imaging for optimally characterize the population), which could provide important inputs to improve the pathophysiological understanding of this complex disease. Well-characterized patients will be randomized according to the management strategy. The primary endpoint will be the occurrence of all-cause mortality or cardiac related-hospitalizations during 2-year FU. One hundred and eighty subjects per group will be included. CONCLUSION: The management of patients with LS severe AS and preserved LVEF is largely debated. ROTAS trial will allow a comprehensive evaluation of this particular pattern of AS and will establish which is the most appropriate management of these patients.

Natural history of functional tricuspid regurgitation: impact of cardiac output.

AIMS: Tricuspid regurgitation (TR) was long forgotten until recent studies alerting on its prognostic impact. Cardiac output (CO) is the main objective of heart mechanics. We sought to compare clinical and echocardiographic data of patients with TR from inclusion to 1-year follow-up according to initial CO. METHODS AND RESULTS: Patients with isolated secondary TR and left ventricular ejection fraction (LVEF) ≥40% were prospectively included. All patients had a clinical and echocardiographic evaluation at baseline and after 1 year. Echocardiographic measurements were centralized. The patients were partitioned according to their CO at baseline. The primary outcome was all-cause death. Ninety-five patients completed their follow-up. The majority of patients had normal CO (n = 64, 67.4%), whereas 16 (16.8%) patients had low-CO and 12 (12.6%) had high-CO. right ventricular function was worse in the low-CO group but with improvement at 1 year (30% increase in tricuspid annular plane systolic excursion). LVEF and global longitudinal strain were significantly worse in the low-CO group. Overall, 18 (19%) patients died during follow-up, of which 10 (55%) patients had abnormal CO. There was a U-shaped association between CO and mortality. Normal CO patients had significantly better survival (87.5% vs. 62.5% and 66.67%) in the low- and high-CO groups, respectively, even after adjustment (heart rate 2.23 for the low-CO group and 9.08 for high-CO group; P = 0.0174). CONCLUSION: Significant isolated secondary TR was associated with 19% of mortality. It is also associated with higher long-term mortality if CO is abnormal, suggesting a possible role for evaluating better and selecting patients for intervention.

Preoperative evaluation in aortic endocarditis: findings on cardiac CT.

OBJECTIVE: The purpose of this study was to study the feasibility and diagnostic capability of preoperative cardiac CT for depicting aortic valvular pseudoaneurysms and vegetations in patients referred for aortic endocarditis requiring surgical intervention. MATERIALS AND METHODS: Consecutive patients presenting with active aortic endocarditis requiring surgical intervention were included. CT scan examinations were performed for assessing coronary artery status. Aortic valves were retrospectively analyzed. Contrast-enhanced CT scans were retrospectively gated to the ECG and obtained without the administration of a beta-blocker. The CT and intraoperative findings were systematically compared. RESULTS: During a 4-year period, 19 consecutive patients (18 men and one woman) were included (mean age +/- SD, 55 +/- 13 years). Results are expressed on a per-patient basis. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT in depicting aortic valve pseudoaneurysms were 100%, 87.5%, 91.7%, and 100%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of the MDCT in depicting the extension of the aortic valve pseudoaneurysms into the intervalvular fibrous body were each 100%. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT in depicting aortic valve vegetations were 71.4%, 100%, 100%, and 55.5%, respectively. The sensitivity, specificity, positive predictive value, and negative predictive value of MDCT for depicting aortic valve vegetations larger than 1 cm were all 100%. CONCLUSION: Our study shows the feasibility of preoperative CT in aortic infective endocarditis for providing relevant data about the presence and relationships of aortic valvular pseudoaneurysms. A larger prospective study including a systematic comparison with transesophageal echocardiography should be performed to determine the respective value of each technique.

Anti-apoptotic peptide for long term cardioprotection in a mouse model of myocardial ischemia-reperfusion injury.

Reperfusion therapy during myocardial infarction (MI) leads to side effects called ischemia-reperfusion (IR) injury for which no treatment exists. While most studies have targeted the intrinsic apoptotic pathway to prevent IR injury with no successful clinical translation, we evidenced recently the potent cardioprotective effect of the anti-apoptotic Tat-DAXXp (TD) peptide targeting the FAS-dependent extrinsic pathway. The aim of the present study was to evaluate TD long term cardioprotective effects against IR injury in a MI mouse model. TD peptide (1 mg/kg) was administered in mice subjected to MI (TD; n = 21), 5 min prior to reperfusion, and were clinically followed-up during 6 months after surgery. Plasma cTnI concentration evaluated 24 h post-MI was 70%-decreased in TD (n = 16) versus Ctrl (n = 20) mice (p***). Strain echocardiography highlighted a 24%-increase (p****) in the ejection fraction mean value in TD-treated (n = 12) versus Ctrl mice (n = 17) during the 6 month-period. Improved cardiac performance was associated to a 54%-decrease (p**) in left ventricular fibrosis at 6 months in TD (n = 16) versus Ctrl (n = 20). In conclusion, targeting the extrinsic pathway with TD peptide at the onset of reperfusion provided long-term cardioprotection in a mouse model of myocardial IR injury by improving post-MI cardiac performance and preventing cardiac remodeling.

Long-term benefit of postconditioning.

BACKGROUND: We previously demonstrated that ischemic postconditioning decreases creatine kinase release, a surrogate marker for infarct size, in patients with acute myocardial infarction. Our objective was to determine whether ischemic postconditioning could afford (1) a persistent infarct size limitation and (2) an improved recovery of myocardial contractile function several months after infarction. METHODS AND RESULTS: Patients presenting within 6 hours of the onset of chest pain, with suspicion for a first ST-segment-elevation myocardial infarction, and for whom the clinical decision was made to treat with percutaneous coronary intervention, were eligible for enrollment. After reperfusion by direct stenting, 38 patients were randomly assigned to a control (no intervention; n=21) or postconditioned group (repeated inflation and deflation of the angioplasty balloon; n=17). Infarct size was assessed both by cardiac enzyme release during early reperfusion and by 201thallium single photon emission computed tomography at 6 months after acute myocardial infarction. At 1 year, global and regional contractile function was evaluated by echocardiography. At 6 months after acute myocardial infarction, single photon emission computed tomography rest-redistribution index (a surrogate for infarct size) averaged 11.8+/-10.3% versus 19.5+/-13.3% in the postconditioned versus control group (P=0.04), in agreement with the significant reduction in creatine kinase and troponin I release observed in the postconditioned versus control group (-40% and -47%, respectively). At 1 year, the postconditioned group exhibited a 7% increase in left ventricular ejection fraction compared with control (P=0.04). CONCLUSIONS: Postconditioning affords persistent infarct size reduction and improves long-term functional recovery in patients with acute myocardial infarction.

Secondary tricuspid regurgitation: Do we understand what we would like to treat?

Tricuspid regurgitation has long been a neglected and underestimated entity; its prevalence is significant, and is increasing with the ageing population. Tricuspid regurgitation is often a consequence of chronic left cardiac pathologies or atrial fibrillation. Surgical treatment is recommended for patients with severe symptomatic tricuspid regurgitation or tricuspid annulus dilatation at the time of left heart valve surgery. Secondary tricuspid regurgitation is a complex disease; this review focuses on the need for better understanding of its mechanisms and quantification - mandatory with the advent of new percutaneous treatments.

Cardiac mGluR1 metabotropic receptors in cardioprotection.

AIMS: In a previous study using a genome-wide microarray strategy, we identified metabotropic glutamate receptor 1 (mGluR1) as a putative cardioprotective candidate in ischaemic postconditioning (PostC). In the present study, we investigated the role of cardiac mGluR1 receptors during cardioprotection against myocardial ischaemia-reperfusion injury in the mouse myocardium. METHODS AND RESULTS: mGluR1 activation by glutamate administered 5 min before reperfusion in C57Bl/6 mice subjected to a myocardial ischaemia protocol strongly decreased both infarct size and DNA fragmentation measured at 24 h reperfusion. This cardioprotective effect was mimicked by the mGluR1 agonist, DHPG (10 µM), and abolished when glutamate was coinjected with the mGluR1 antagonist YM298198 (100 nM). Wortmannin (100 nM), an inhibitor of PI3-kinase, was able to prevent glutamate-induced cardioprotection. A glutamate bolus at the onset of reperfusion failed to protect the heart of mGluR1 knockout mice subjected to a myocardial ischaemia-reperfusion protocol, although PostC still protected the mGluR1 KO mice. Glutamate-treatment improved post-infarction functional recovery as evidenced by an echocardiographic study performed 15 days after treatment and by a histological evaluation of fibrosis 21 days post-treatment. Interestingly, restoration of functional mGluR1s by a PostC stimulus was evidenced at the transcriptional level. Since mGluR1s were localized at the surface membrane of cardiomyocytes, they might contribute to the cardioprotective effect of ischaemic PostC as other Gq-coupled receptors. CONCLUSION: This study provides the first demonstration that mGluR1 activation at the onset of reperfusion induces cardioprotection and might represent a putative strategy to prevent ischaemia-reperfusion injury.

Mitral valve repair by Alfieri's technique does not limit exercise tolerance more than Carpentier's correction.

OBJECTIVE: The main goal of this study was to evaluate if the edge-to-edge mitral repair could be a limiting factor for exercise tolerance and to compare these results to those of classical techniques. METHODS: Between 2000 and 2002, 54 consecutive patients were operated on for mitral valve regurgitation (MR). Twenty-five patients were operated with Alfieri's technique (group A) and 29 patients with Carpentier's technique (group C). The mean age was 63.9 years in group A and 63.8 years in group C (p = 0.98). After a mean follow-up of 16.2+/-12 months, survivor patients were seen at the outpatient clinic, by the same physician for a clinical evaluation, an echocardiogram at rest and at peak exercise, and received a cardiorespiratory exercise testing with maximal oxygen uptake (VO2 max) recording. RESULTS: Clinical status improved with 0% of the patients in class NYHA III or IV in either group postoperatively versus 77% preoperatively. There was no significant MR in 80% of cases in group A versus 89.6% in group C (p = 0.54). The mean mitral valve area was 2.5 and 2.9 cm2 in groups A and C, respectively (p = 0.018). The mitral gradient at rest was 3.8 and 3.3 mmHg (p = 0.31) and the mitral gradient at peak exercise was 8.5 and 9.7 mmHg (p = 0.22) in groups A and C, respectively. Cardiorespiratory exercise testing showed a mean VO2 max of 73.7+/-15% of normal value in group A versus 79.6+/-13.1% in group C (p = 0.18). CONCLUSION: Alfieri's technique has the same efficiency on improvement of MR and clinical status than classical repair. Despite a higher restriction of mitral valve area at rest in group A, gradient and mean VO2 max at peak exercise were similar in both groups.

Difference in mobilization of progenitor cells after myocardial infarction in smoking versus non-smoking patients: insights from the BONAMI trial.

INTRODUCTION: Although autologous bone marrow cell (BMC) therapy has emerged as a promising treatment for acute myocardial infarction (AMI), trials reported mixed results. In the BONAMI trial, active smoking reduced cardiac function recovery after reperfused AMI. Therefore, we hypothesized that variability in the functionality of BMCs retrieved from patients with cardiovascular risk factors may partly explain these mixed results. We investigated the characteristics of progenitor cells in active smokers and non-smokers with AMI and their potential impact on BMC therapy efficacy. METHODS: Bone marrow and blood samples from 54 smoking and 47 non-smoking patients enrolled in the BONAMI cell therapy trial were analyzed. RESULTS: The white BMC and CD45dimCD34+ cell numbers were higher in active smokers (P = 0.001, P = 0.03, respectively). In marked contrast, either bone marrow or blood endothelial progenitor CD45dimCD34 + KDR + cells (EPCs) were decreased in active smokers (P = 0.005, P = 0.04, respectively). Importantly, a multivariate analysis including cardiovascular risk factors confirmed the association between active smoking and lower EPC number in bone marrow (P = 0.04) and blood (P = 0.04). Furthermore, baseline circulating EPC count predicted infarct size decrease at three months post-AMI in non-smokers (P = 0.01) but not in active smokers. Interestingly, baseline circulating EPCs were no longer predictive of cardiac function improvement in the BMC therapy group. CONCLUSIONS: These data suggest that circulating EPCs play an important role in cardiac repair post-AMI only in non-smokers and that active smoking-associated EPC alterations may participate in the impairment of cardiac function recovery observed in smokers after AMI, an effect that was overridden by BMC therapy.

Post-conditioning reduces infarct size and edema in patients with ST-segment elevation myocardial infarction.

OBJECTIVES: This study aimed to determine whether post-conditioning at the time of percutaneous coronary intervention could reduce reperfusion-induced myocardial edema in patients with acute ST-segment elevation myocardial infarction (STEMI). BACKGROUND: Myocardial edema is a reperfusion injury with potentially severe consequences. Post-conditioning is a cardioprotective therapy that reduces infarct size after reperfusion, but no previous studies have analyzed the impact of this strategy on reperfusion-induced myocardial edema in humans. METHODS: Fifty patients with STEMI were randomly assigned to either a control or post-conditioned group. Cardiac magnetic resonance imaging was performed within 48 to 72 h after admission. Myocardial edema was measured by T2-weighted sequences, and infarct size was determined by late gadolinium enhancement sequences and creatine kinase release. RESULTS: The post-conditioned and control groups were similar with respect to ischemia time, the size of the area at risk, and the ejection fraction before percutaneous coronary intervention. As expected, post-conditioning was associated with smaller infarct size (13 ± 7 g/m(2) vs. 21 ± 14 g/m(2); p = 0.01) and creatine kinase peak serum level (median [interquartile range]: 1,695 [1,118 to 3,692] IU/l vs. 3,505 [2,307 to 4,929] IU/l; p = 0.003). At reperfusion, the extent of myocardial edema was significantly reduced in the post-conditioned group as compared with the control group (23 ± 16 g/m(2) vs. 34 ± 18 g/m(2); p = 0.03); the relative increase in T2W signal intensity was also significantly lower (p = 0.02). This protective effect was confirmed after adjustment for the size of the area at risk. CONCLUSIONS: This randomized study demonstrated that post-conditioning reduced infarct size and edema in patients with reperfused STEMI.

Effect of cyclosporine on left ventricular remodeling after reperfused myocardial infarction.

OBJECTIVES: This study examined the effect of a single dose of cyclosporine administered at the time of reperfusion on left ventricular (LV) remodeling and function by cardiac magnetic resonance 5 days and 6 months after myocardial infarction. BACKGROUND: In a human study, administration of cyclosporine at the time of acute reperfusion was associated with a smaller infarct size. METHODS: Twenty-eight patients of the original cyclosporine study had an acute (at 5 days) and a follow-up (at 6 months) cardiac magnetic resonance study to determine LV volumes, mass, ejection fraction, myocardial wall thickness in infarcted and remote noninfarcted myocardium, and infarct size. RESULTS: There was a persistent reduction in infarct size at 6 months in the cyclosporine group compared with the control group of patients (29 +/- 15 g vs. 38 +/- 14 g; p = 0.04). There was a significant reduction of LV end-systolic volume (and a trend for LV end-diastolic volume; p = 0.07) in the cyclosporine group compared with the control group, both at 5 days and 6 months after infarction. There was no significant difference between the 2 groups in either global LV mass or regional wall thickness of the remote noninfarcted myocardium at 5 days or 6 months. Attenuation of LV dilation and improvement of LV ejection fraction by cyclosporine at 6 months were correlated with infarct size reduction. CONCLUSIONS: Cyclosporine used at the moment of acute myocardial infarction reperfusion persistently reduces infarct size and does not have a detrimental effect on LV remodeling. These results are preliminary and must be supported by further studies. (Ciclosporin A and Acute Myocardial Infarction; NCT00403728).