Impact of Obstructive Sleep Apnea Syndrome on Ventricular Remodeling after Acute Myocardial Infarction: A Proof-of-Concept Study.

Background: Obstructive sleep apnea syndrome (OSA) is common in patients with acute myocardial infarction (AMI). Whether OSA impacts on the ventricular remodeling post-AMI remains unclear. We compared cardiac ventricular remodeling in patients assessed by cardiac magnetic resonance (CMR) imaging at baseline and six months after AMI based on the presence and severity of OSA. Methods: This prospective study included 47 patients with moderate to severe AMI. They all underwent CMR at inclusion and at six months after an AMI, and a polysomnography was performed three weeks after AMI. Left and right ventricular remodeling parameters were compared between patients based on the AHI, AHI in REM and NREM sleep, oxygen desaturation index, and daytime sleepiness. Results: Of the 47 patients, 49% had moderate or severe OSA with an AHI ≥ 15/h. No differences were observed between these patients and those with an AHI < 15/h for left ventricular end-diastolic and end-systolic volumes at six months. No association was found for left and right ventricular remodeling parameters at six months or for the difference between baseline and six months with polysomnographic parameters of OSA severity, nor with daytime sleepiness. Conclusions: Although with a limited sample size, our proof-of-concept study does not report an association between OSA and ventricular remodeling in patients with AMI. These results highlight the complexity of the relationships between OSA and post-AMI morbi-mortality.

Impact of Daily Bedside Echocardiographic Assessment on Readmissions in Acute Heart Failure: A Randomized Clinical Trial.

Acute heart failure (AHF) management is challenging, with high morbidity and readmission rates. There is little evidence of the benefit of HF monitoring during hospitalization. The aim of the study was to assess whether daily bedside echocardiographic monitoring (JetEcho) improved outcomes in AHF. In this prospective, open, two parallel-arm study (clinicaltrials.gov: NCT02892227), participants from two university hospitals were randomized to either standard of care (SC) or daily treatment adjustment including diuretics guided by JetEcho evaluating left ventricular filling pressure and volemia. The primary outcome was 30-day readmission rate. Key secondary outcomes were six-month cumulative incidence death, worsening HF during hospitalization and increasing of myocardial and renal biomarkers. From 250 included patients, 115 were finally analyzed in JetEcho group and 112 in SC group. Twenty-two (19%) patients were readmitted within 30 days in JetEcho group and 17 (15%) in SC group (relative risk [RR] 1.26; 95% confidence interval [CI], 0.70−2.24; p = 0.4). Worsening HF occurred in 17 (14%) patients in the JetEcho group and 24 (20%) in the SC group (RR 0.7; 95% [CI] 0.39 to 1.2; p = 0.2). No significant difference was found between the two groups concerning natriuretic peptides and renal function (p > 0.05 for all). The cumulative incidence rate of death from any cause at six months from discharge was 8.7% in the JetEcho group and 11.6% in the SC group (HR 0.63, 95% [CI] 0.3−1.4, p = 0.3). In AHF patients, a systematic daily bedside echocardiographic monitoring did not reduce 30-day readmission rate for HF and short-term clinical outcomes.

Conception and bicentric validation of the proSCANNED score, a simplified bedside prognostic score for Heart Failure patients.

A simple and accurate prognostic tool for Heart Failure (HF) patients is critical to improve follow-up. Different risk scores are accurate but with limited clinical applicability. The current study aims to derive and validate a simple predictive tool for HF prognosis. French outpatients with stable HF of two university hospitals were included in the derivation (N = 134) or in the validation (N = 274) sample and followed up for a median of 23 months. Potential predictors were variables with known association with mortality and easily available. The proSCANNED risk score was derived using a parametric survival model on complete case data; it includes 8 binary variables and its values are 0-8. In the validation sample, the ability of the score to discriminate the 1-year vital status was moderate (AUC = 0.71, IC95% = [0.64-0.71]). However, the stratification of the score in three groups showed a good calibration for patients in the low- and medium-risk risk group. The proSCANNED score is an easy-to-use tool in clinical practice with a good discrimination, stability, and calibration sufficient to improve the medical care of patients. Other follow up studies are necessary to assess score applicability in larger populations, and its impact.

Exploring collagen remodeling and regulation as prognosis biomarkers in stable heart failure.

We assessed the predictive ability of circulating biomarkers involved in collagen synthesis (procollagen type I N-terminal propeptide [PINP], and procollagen type III N-terminal propeptide [PIIINP], collagen degradation (c-terminal telopeptide of collagen type I [CTx] and mediators of cardiac fibrosis (Galectin-3 and soluble suppression of tumorigenicity 2 protein or sST2) as prognosis markers in 182 subjects with chronic heart failure (HF). In univariate analysis, all markers predicted mortality (except for PINP). A multivariate baseline model was fitted including variables potentially associated with mortality in HF patients. The baseline regression model included age, clinical data and biomarkers. We created four models from the baseline model augmented with the levels of hs-cTnT, CRP and NT-proBNP (model 1), CTx/PIIINP ratio, sST2 and Galectine-3 (model 2), NT-proBNP and sST2 (model 3) and NT-proBNP, CTx/PIIINP ratio and sST2 (model 4), to test whether these biomarkers have an incremental value for predicting mortality. After the addition of all biomarkers to the baseline model, age, CTx/PIIINP ratio and sST2 remained significant predictors. By contrast, Galectin-3 was not significantly associated with mortality. A multimarker strategy, demonstrated that the greatest prognostic improvement was attained with the combined addition of CTx/PIIINP ratio and sST2 highlighting the potential role of fibrosis pathways in risk stratification.

Management of acute heart failure: Contribution of daily bedside echocardiographic assessment on therapy adjustment with impact measure on the 30-day readmission rate (JECICA).

There are currently one million heart failure (HF) patients in France and the rate is progressively increases due to population aging. Acute decompensation of HF is the leading cause of hospitalization in people over 65 years of age with a 25% re-hospitalization rate in the first month. Expenses related to the management of HF in France in 2013 amounted to more than one billion euros, of which 65% were for hospitalizations alone. The management of acute decompensation is a challenge, due to the complexity of clinical and laboratory evaluation leading to therapeutic errors, which in turn leads to longer hospitalization, high early re-hospitalization and complications. Therapeutic adjustment, especially diuretic, in the acute phase (during hospitalization) affects early re-hospitalization rates (within 30 days). These adjustments can be based on clinical estimation and laboratory parameters, but echocardiography has been shown to be superior in estimating filling pressures (FP) compared to clinical and laboratory parameters. We hypothesize that a simple daily bedside echocardiographic assessment could provide a reproducible estimation of FP with an evaluation of mitral inflow and the inferior vena cava (IVC). This could allow a more reliable estimate of the true blood volume of the patient and thus lead to a more suitable therapeutic adjustment. This in turn should lead to a decrease in early re-admission rate (primary endpoint) and potentially decrease six-month mortality and rate of complications.

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.

The Intensity of Primary Care for Heart Failure Patients: A Determinant of Readmissions? The CarPaths Study: A French Region-Wide Analysis.

BACKGROUND: We aimed to classify patients with heart failure (HF) by the style of primary care they receive. METHODS AND RESULTS: We used the claim data (SNIIRAM: Système National d'Information Inter-Régime de l'Assurance Maladie) of patients living in a French region. We evaluated three concepts. First, baseline clinical status with age and Charlson index. Second, primary care practice style with mean delay between consultations, quantity of nursing care, and variability of diuretic dose. Third, clinical outcomes with death during follow-up, readmission for HF, and rate of unforeseen consultations. The baseline clinical status and the clinical outcomes were included to give an insight in the reasons for, and performance of, primary care practice style. Patients were classified using a hierarchical ascending classification based on principal components. A total of 2,751 patients were included in this study and were followed for a median of 22 months. The mean age was 78 y (SD: 12); 484 (18%) died, and 818 (30%) were readmitted for HF. We found three different significant groups characterized by their need for care and the intensity of practice style: group 1 (N = 734) was "low need-low intensity"; group 2 (N = 1,060) was "high need-low intensity"; and group 3 (N = 957) was "high need-high intensity". Their readmission rates were 17%, 41% and 28%, respectively. CONCLUSIONS: This study evaluated the link between primary care, clinical status and main clinical outcomes in HF patients. In higher need patients, a low-intensity practice style was associated with poorer clinical outcomes.

The Influence of Arm Positioning on Ultrasonic Visualization of the Subclavian Vein: An Anatomical Ultrasound Study in Healthy Volunteers.

We hypothesized that placing the arm in 90° abduction, through 90° flexion and 90° external rotation, could improve ultrasound visualization of the subclavian vein. In 49 healthy volunteers, a single operator performed a view of the subclavian vein in neutral position and abduction position. A second blinded operator measured the cross-sectional area of the subclavian vein. Abduction position increased the cross-sectional area of the subclavian vein from 124 ± 46 (mean ± SD) to 162 ± 58 mm (P = 0.001). An increase of the cross-sectional area of ≥50% was observed in 41% volunteers (95% confidence interval, 27%-56%, n = 20); this technique offers an alternative approach (maybe safer) for ultrasound-guided catheterization of the subclavian vein.

Kinetics of high-sensitivity cardiac troponin T and I differ in patients with ST-segment elevation myocardial infarction treated by primary coronary intervention.

PURPOSE: Cardiac biomarkers including troponins are the cornerstone of the biological definition of acute myocardial infarction. New high-sensitivity cardiac assays determining troponin T (hs-cTnT) as well as I ((hs-cTnI) from Abbott and s-cTnI from Siemens) raise concerns because of their unclear kinetics following the peak. AIMS: This study aims to compare kinetics of creatine kinases, hs-cTnT, hs-cTnI and s-cTnI in patients with ST-segment elevation myocardial infarction (STEMI) treated by percutaneous coronary intervention. METHODS: We prospectively studied 106 consecutive patients admitted in our institution for STEMI and treated by percutaneous coronary intervention. We evaluated for all the patients simultaneously kinetics of creatine kinases, hs-cTnT (Roche) and two different cTnIs (hs-cTnI from Abbott and s-cTnI from Siemens). Modelling of kinetics was realized using mixed effects with cubic splines. RESULTS: Kinetics of markers showed a first peak at 10.7h (8.0-12.0) for creatine kinases, 11.8h (10.4-13.3) for hs-cTnT (Roche); 11.8h (10.7-11.8) for hs-cTnI from Abbott and 10.2h (8.7-11.6) for s-cTnI from Siemens, respectively. This peak was followed by a nearly log linear decrease for hs-cTnI/s-cTnI and creatine kinases in contrast to hs-cTnT, which appeared with a biphasic shape curve marked by a second peak at 76.9h (69.5-82.8). The analysis of the decrease in percentage of the peak value at 77h showed that hs-cTnT follows a twice lower decrease than other markers. CONCLUSION: Kinetics of hs-cTnT, hs-cTnI and s-cTnI differ significantly with a linear decrease regarding both cTnI assays contrasting with a biphasic shape curve for hs-cTnT. This is of importance for clinical management of patients in routine settings especially in follow-up after STEMI including the suspicion of reinfarction.

Kinetics of high-sensitivity cardiac troponin T or troponin I compared to creatine kinase in patients with revascularized acute myocardial infarction.

BACKGROUND: Cardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI). METHODS: We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines. RESULTS: Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9-12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1-99.9) vs. cTnI by 86.8% (76.6-92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9-42.9) when compared with CK that fell by 79.5% (64.3-90.7). CONCLUSIONS: Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.