Christophe de Meester de Ravenstein

Prognostic Significance of LGE by CMR in Aortic Stenosis Patients Undergoing Valve Replacement

BACKGROUND Prior studies have shown that late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) can detect focal fibrosis in aortic stenosis (AS), suggesting that it might predict higher mortality risk. OBJECTIVES This study was conducted to evaluate whether LGE-CMR can predict post-operative survival in patients with severe AS undergoing aortic valve replacement (AVR). METHODS We prospectively evaluated survival (all-cause and cardiovascular disease related) according to LGE-CMR status in 154 consecutive AS patients (96 men; mean age: 74 ± 6 years) without a history of myocardial infarction undergoing surgical AVR and in 40 AS patients undergoing transcatheter aortic valve replacement (TAVR). RESULTS LGE was present in 29% of patients undergoing surgical AVR and in 50% undergoing TAVR. During a median follow-up of 2.9 years, 21 patients undergoing surgical AVR and 20 undergoing TAVR died. In surgical AVR, the presence of LGE predicted higher post-operative mortality (odds ratio: 10.9; 95% confidence interval [CI]: 1.2 to 100.0; p = 0.02) and worse all-cause survival (73% vs. 88%; p = 0.02 by log-rank test) and cardiovascular disease related survival (85% vs. 95%; p = 0.03 by log-rank test) on 5-year Kaplan-Meier estimates of survival after surgical AVR. Multivariate Cox analysis identified the presence of LGE (hazard ratio: 2.8; 95% CI: 1.3 to 6.9; p = 0.025) and New York Heart Association functional class III/IV (hazard ratio: 3.2; 95% CI: 1.1 to 8.1; p < 0.01) as the sole independent predictors of all-cause mortality after surgical AVR. The presence of LGE also predicted higher all-cause mortality (p = 0.05) and cardiovascular disease related mortality (p = 0.03) in the subgroup of patients without angiographic coronary artery disease (n = 110) and higher cardiovascular disease related mortality in 25 patients undergoing transfemoral TAVR. CONCLUSIONS The presence of LGE indicating focal fibrosis or unrecognized infarct by CMR is an independent predictor of mortality in patients with AS undergoing AVR and could provide additional information in the pre-operative evaluation of risk in these patients.

Aortic Valve Area, Stroke Volume, Left Ventricular Hypertrophy, Remodeling, and Fibrosis in Aortic Stenosis Assessed by Cardiac Magnetic Resonance Imaging Comparison Between High and Low Gradient and Normal and Low Flow Aortic Stenosis

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) <0.6 cm2/m2 and ejection fraction >50% by echocardiography underwent CMR to measure planimetric AVA, phase-contrast indexed stroke volume, LV mass, and focal fibrosis. Using <40 mm Hg and indexed stroke volume <35 mL/m2 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<0.001 for all). By CMR, however, planimetric AVA was larger in LF/LG (0.54±0.08 cm2/m2) and LG/NF (0.61±0.08 cm2/m2) than in HG/LF (0.46±0.07 cm2/m2; P<0.05) AS, and indexed LV mass was lower in LG/LF (75±12 g/m2) and LG/NF (81±18 g/m2) than in HG/LF (100±27 g/m2; P<0.05) AS. All groups of AS had similar LV volumes, predominantly concentric hypertrophy remodeling, and similar amounts of focal fibrosis. 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.

Sodium-myoinositol cotransporter-1, SMIT1, mediates the production of reactive oxygen species induced by hyperglycemia in the heart.

Hyperglycemia (HG) stimulates the production of reactive oxygen species in the heart through activation of NADPH oxidase 2 (NOX2). This production is independent of glucose metabolism but requires sodium/glucose cotransporters (SGLT). Seven SGLT isoforms (SGLT1 to 6 and sodium-myoinositol cotransporter-1, SMIT1) are known, although their expression and function in the heart remain elusive. We investigated these 7 isoforms and found that only SGLT1 and SMIT1 were expressed in mouse, rat and human hearts. In cardiomyocytes, galactose (transported through SGLT1) did not activate NOX2. Accordingly, SGLT1 deficiency did not prevent HG-induced NOX2 activation, ruling it out in the cellular response to HG. In contrast, myo-inositol (transported through SMIT1) reproduced the toxic effects of HG. SMIT1 overexpression exacerbated glucotoxicity and sensitized cardiomyocytes to HG, whereas its deletion prevented HG-induced NOX2 activation. In conclusion, our results show that heart SMIT1 senses HG and triggers NOX2 activation. This could participate in the redox signaling in hyperglycemic heart and contribute to the pathophysiology of diabetic cardiomyopathy.

Early prognosis and predictor analysis for positive coronary angiography after out-of-hospital cardiac arrest (OHCA).

Abstract Background: Key predictors of survival after OHCA have been described in the literature. Current guidelines recommend emergency angiography in patients without an obvious extra-cardiac cause of arrest. However, the value of this strategy is debated. Moreover, diagnosis of acute coronary ischaemia after OHCA remains challenging, especially in patients without ST-segment elevation. Objectives: The primary objective was to identify qualitative variables associated with an increased chance of 30-d survival after OHCA. The secondary objective was to identify predictors of 30-d survival among patients with ischaemic cardiomyopathy and patients without ST-segment elevation. Afterwards, we sought to identify parameters associated with acute coronary ischaemia and positive coronary angiography in patients without ST-segment elevation. Methods: Retrospective single-centre study including 123 patients resuscitated from OHCA. Baseline characteristics, resuscitation settings and angiographic findings were analysed. Results: The predictors of 30-d survival after OHCA included witnessed cardiac arrest, haemodynamic instability and coronary angiography. Convertible cardiac rhythm, history of coronary disease and presence of at least two cardiovascular risk factors were associated with acute coronary ischaemia. Predictors for a positive angiography in patients without ST-segment elevation included history of coronary disease, gender, diabetes, dyslipidaemia and presence of at least two cardiovascular risk factors (all p < .05). Conclusions: We identified qualitative predictors of 30-day survival after OHCA. Our findings suggest that the recognition of acute coronary ischaemia after OHCA might be improved. The identification of risk criteria may help to select the best candidates for emergency angiography.

Pulmonary hypertension due to left heart disease: diagnostic and prognostic value of CT in chronic systolic heart failure

ObjectivesTo evaluate the ability of chest computed tomography (CT) to predict pulmonary hypertension (PH) and outcome in chronic heart failure with reduced ejection fraction (HFrEF).MethodsWe reviewed 119 consecutive patients with HFrEF by CT, transthoracic echocardiography (TTE) and right heart catheterization (RHC). CT-derived pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio), left atrial, right atrial, right ventricular (RV) and left ventricular volumes were correlated with RHC mean pulmonary arterial pressure (mPAP) . Diagnostic accuracy to predict PH and ability to predict primary composite endpoint of all-cause mortality and HF events were evaluated.ResultsRV volume was significantly higher in 81 patients with PH compared to 38 patients without PH (133 ml/m2 vs. 79 ml/m2, p < 0.001) and was moderately correlated with mPAP (r=0.55, p < 0.001). Also, RV volume had higher ability to predict PH (area under the curve: 0.88) than PA diameter (0.79), PA:A ratio (0.76) by CT and tricuspid regurgitation gradient (0.83) and RV basal diameter by TTE (0.84, all p < 0.001). During the follow-up period (median: 3.4 years), 51 patients (43%) had HF events or died. After correction for important clinical, TTE and RHC parameters, RV volume (adjusted hazard ratio [HR]: 1.71, 95% CI 1.31–2.23, p < 0.001) and PA diameter (HR: 1.61, 95% CI 1.18–2.22, p = 0.003) were independent predictors of the primary endpoint.ConclusionIn patients with HFrEF, measurement of RV volume and PA diameter on ungated CT are non-invasive markers of PH and may help to predict the patient outcome.Key Points• Right ventricular (RV) volume measured by chest CT has good ability to identify pulmonary hypertension (PH) in patients with chronic heart failure (HF) and reduced ejection fraction (HFrEF).• The accuracy of pulmonary artery (PA) diameter and PA to ascending aorta diameter ratio (PA:A ratio) to predict PH was similar to previous studies, however, with lower cut-offs (28.1 mm and 0.92, respectively).• Chest CT-derived PA diameter and RV volume independently predict all-cause mortality and HF events and improve outcome prediction in patients with advanced HFrEF.

Relative contribution of afterload and interstitial tissue fibrosis to preoperative longitudinal function in patients with severe aortic stenosis: implications for postoperative functional recovery

Background: Several previous studies have demonstrated that, in patients with severe aortic stenosis (SAS), chronic pressure overload hypertrophy frequently results in reduced longitudinal function as assessed by tissue Doppler or speckle tracking echocardiography (STE). The aim of the present study was to determine the relative contribution of structural (interstitial fibrosis) and functional (afterload) alterations in this process and to evaluate the implications thereof for functional recovery after aortic valve replacement (AVR). Methods: 34 patients with isolated SAS underwent pre-operative resting conventional echocardiography and STE, to calculate end-systolic wall stress (ESS) and to measure global longitudinal strain (GLS) and left ventricular ejection fraction (LVEF). At the time of AVR, a per-operative transmural biopsy was obtained in every patient, to quantify the degree of interstitial fibrosis. Echocardiographic functional parameters were reassessed 6 months after AVR. Results: Compared to age-matched normal controls, SAS patients exhibited significantly reduced GLS (-12.5 ± 3.9% vs -18.2 ± 1.5% p<0.0001) and LVEF (57 ± 13 vs 66 ± 4%, p=0.026). With univariate analysis, pre-operative GLS was found to correlate significantly with LVEF (r=0.70, p<0.0001), interstitial fibrosis (r=-0.60, p=0.0002), LV mass (r=-0.52, p=0.002) and ESS (r=-0.61, p=0.0001). Using stepwise multiple regression analysis, only the degree of interstitial fibrosis and ESS were found to be independent correlates of pre-operative GLS (r=0.74). Interestingly,unstressed pre-operative GLS, extrapolated as GLS at zero stress, correlated well with interstitial fibrosis (r=0.51) and predicted GLS at the 6-months post-operative follow-up (r=0.55). Conclusions: In patients with SAS, reduced longitudinal function results from both excessive afterload and structural tissue alterations (interstitial fibrosis). Unstressed pre-operative GLS was found to be a reasonable correlate of tissue fibrosis and to allow prediction of long term post-operative longitudinal function.