QSOX1, a novel actor of cardiac protection upon acute stress in mice.

QSOX1, a sulfhydryl oxidase, was shown to be upregulated in the heart upon acute heart failure (AHF). The aim of the study was to unravel QSOX1 roles during AHF. We generated and characterized mice with QSOX1 gene deletion. The QSOX1-/- mice were viable but adult male exhibited a silent dilated cardiomyopathy. The QSOX1-/- hearts were characterized by low protein SERCA2a levels associated with a calcium homeostasis alteration, high levels of the endoplasmic reticulum (ER) chaperone proteins Grp78/Bip, and of the ER apoptosis sensor CHOP, indicating a chronic unfolded protein response (UPR). Importantly the QSOX1invalidation led to overexpression of two ER oxidases, ERO1-α and PRDX4. Acute stress was induced by isoproterenol injection (ISO, 300 mg/kg/12 h) for 2 days. In both groups, the PERK UPR pathway was transiently activated 6 h after the first ISO injection as indicated by eIF2 phosphorylation. By day-3 after the onset of stress, both WT and QSOX1-/- mice exhibited AHF profile but while high cardiac QSOX1 level was induced in WT hearts, ERO1-α and PRDX4 levels drop down in QSOX1-/-. At that time, QSOX1-/- hearts exhibited an enhanced inflammation (CD68+ cells and Galectin-3 expression) and oxidative stress (DHE staining and oxyblot) when compared to WT ones. In conclusion, the lack of QSOX1 promotes the upregulation of two ER oxidases ERO1α and PRDX4 that likely rescues oxidative protein folding in the hearts. However, signs of chronic ER stress remained present and were associated with a dilated cardiomyopathy. The superimposition of acute stress allowed us to propose that QSOX1 participate to the early response to cardiac stress but not to immediate UPR response. Taken altogether, the data indicated that QSOX1 is required 1) for a proper protein folding in the endo/sarcoplasmic reticulum (ER/SR) and 2) for resolution and protective response during acute stress.

Unicuspid aortic valve by cardiac computed tomography: the best view is from the mountaintop-a case report.

Background: Unicuspid aortic valve (UAV) is a rare valvular heart disease and a challenging diagnosis. Advanced imaging techniques, particularly cardiac computed tomography (CT), appear to be invaluable tools to correctly identify this disease pre-operatively, as this may have an impact on the optimal surgical treatment. Case summary: We describe the case of a young patient admitted with heart failure, due to a severely stenotic UAV. Cardiac CT allowed adjusting the imaging plane to the best view in two orthogonal planes to identify the top of the 'dome' and to accurately measure the smallest valve opening by planimetry. Surgical inspection confirmed a rare case of acommissural UAV. Discussion: Cardiac CT angiography is crucial to understand the complexity of UAV disease and to differentiate the acommissural from the unicommissural type. Accurate positioning of the imaging plane through the smallest valve opening in systole reduces the risk of missing the diagnosis of this rare disease.

Transoesophageal echocardiography current practice in France: A multicentre study.

BACKGROUND: Few data are available on the application of transoesophageal echocardiography (TOE) recommendations in daily practice. AIMS: To evaluate TOE practice based on echocardiography societies' guidelines, and to determine complication rates and factors associated with patient feelings. METHODS: Between April and June 2017, we prospectively included all consecutive patients referred to 14 French hospitals for a transoesophageal echocardiogram (TOE). A survey was taken just after the examination, which included questions about pre-procedural anxiety, and any pain, unpleasant feeling or breathing difficulties experienced during the examination. RESULTS: Overall, 1718 TOEs were performed, mainly for stroke evaluation. A standardized operating procedure checklist was completed in half of the patients before the examination. TOE was unpleasant for 62.4% of patients, but was stopped for agitation or intolerance in 3.5 and 1.4% of cases, respectively. We observed one severe complication (pulmonary oedema). The mean TOE duration was short (9.2±4.6minutes), but was longer with residents than with more experienced physicians (11±4.7 vs. 8.8±4.7minutes for junior physicians [P=0.0027]; vs. 8.9±4.8minutes for senior physicians [P=0.0013]; and vs. 7.5±4.1minutes for associate professors/professors [P<0.0001]). The visual analogue scale (VAS) score after TOE was good (8.3±1.7 out of 10), and was better in patients with general anaesthesia (GA) than in those without GA (9.3±0.9 vs. 8.1±1.7; P<0.0001). In patients without GA, the VAS score was similar with and without local anaesthesia (8.1±1.7 vs. 8.2±1.6; P=0.19). After multivariable adjustment, absence of anxiety before TOE and greater operator experience were consistently associated with a higher VAS score. CONCLUSIONS: TOE is safe, with a low rate of complications and few stops for intolerance. A shorter TOE duration and better patient feelings were observed for experienced operators, highlighting the importance of the learning curve, and paving the way for teaching on a TOE simulator.

High body mass index is a predictor of left ventricular reverse remodelling in heart failure with reduced ejection fraction.

AIMS: Structural and functional left ventricular alterations can occur in heart failure (HF), referred to as left ventricular reverse remodelling (LVRR). This study aimed to define novel predictors of LVRR besides well-known effects of medical and device therapy. METHODS AND RESULTS: From echographic database, we included 295 patients with both left ventricular ejection fraction (LVEF) ≤45% and indexed left ventricular end-diastolic diameter ≥33 mm/m2 and who had at least two echocardiographic exams with a delay between 3 and 12 months. LVRR was defined as the combination of (i) normalization of LVEF (LVEF ≥50%) or increase in LVEF ≥10% and (ii) a decrease in indexed left ventricular end-diastolic diameter ≥10%. Clinical follow-up was also obtained. LVRR occurred in 53 (18%) patients. Patients in the LVRR group were more likely to present with de novo HF (75% vs. 42%), had lower LVEF and left ventricular end-diastolic volumes at index examination, yet a higher body mass index (BMI) than non-LVRR patients. Obesity was observed in 25% of LVRR patients vs. 14% in others. In multivariate analyses, BMI (per each 1 kg/m2 increase) emerged as a predictor of LVRR: odds ratio 1.10 (95% confidence interval 1.02-1.19) after adjustment to other predictors of LVRR. During a mean follow-up of 37 months, 32% of patients had a major adverse cardiac event; de novo HF, age, and LVEF were associated with major adverse cardiac event. CONCLUSIONS: We identified significant relationship between high BMI and LVRR. This intriguing novel finding deserves further study.