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In the stratification of potential causes of PH, current guidelines recommend performing V/Q lung scintigraphy to screen for CTEPH. The recognition of CTEPH is based on the identification of lung segments or sub-segments without perfusion but preserved ventilation. The presence of mismatched perfusion defects has also been described in a small proportion of idiopathic pulmonary arterial hypertension (PAH) and pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis (PVOD/PCH). Dual-energy CT lung perfusion changes have not been specifically investigated in these two entities.To compare dual-energy CT (DECT) perfusion characteristics in PAH and PVOD/PCH, with specific interest in PE-type perfusion defects.Sixty-three patients with idiopathic or heritable PAH (group A; n = 51) and PVOD/PCH (group B; n = 12) were investigated with DECT angiography with reconstruction of morphologic and perfusion images.The number of patients with abnormal perfusion did not differ between group A (35/51; 68.6%) and group B (6/12; 50%) (p = 0.31) nor did the mean number of segments with abnormal perfusion per patient (group A: 17.9 ± 4.9; group B: 18.3 ± 4.1; p = 0.91). The most frequent finding was the presence of patchy defects in group A (15/35; 42.9%) and a variable association of perfusion abnormalities in group B (4/6; 66.7%). The median percentage of segments with PE-type defects per patient was significantly higher in group B than in group A (p = 0.041). Two types of PE-type defects were depicted in 8 patients (group A: 5/51; 9.8%; group B: 3/12; 25%), superimposed on PH-related lung abnormalities (7/8) or normal lung (1/8). The iodine concentration was significantly lower in patients with abnormal perfusion (p0.001) but did not differ between groups.Perfusion abnormalities did not differ between the two groups at the exception of a higher median percentage of segments with PE-type defects in patients with PVOD/PCH.• Patchy perfusion defect was the most frequent pattern in PAH. • A variable association of perfusion abnormalities was seen in PVOD/PCH. • Lobular and PE-type perfusion defects larger than a sub-segment were depicted in both PAH and PVOD/PCH patients.

Background & Aims Long-term outcomes in portopulmonary hypertension (PoPH) are poorly studied in the current era of pulmonary hypertension management. We analysed the effect of pulmonary arterial hypertension (PAH)-targeted therapies, survival and predictors of death in a large contemporary cohort of patients with PoPH. Methods Data from patients with PoPH consecutively enrolled in the French Pulmonary Hypertension Registry between 2007 and 2017 were collected. The effect of initial treatment strategies on functional class, exercise capacity and cardiopulmonary haemodynamics were analysed. Survival and its association with PAH- and hepatic-related characteristics were also examined. Results Six hundred and thirty-seven patients (mean age 55 ± 10 years; 58% male) were included. Fifty-seven percent had mild cirrhosis, i.e. Child-Pugh stage A. The median model for end-stage liver disease (MELD) score was 11 (IQR 9–15). Most patients (n = 474; 74%) were initiated on monotherapy, either with a phosphodiesterase-5 inhibitor (n = 336) or with an endothelin-receptor antagonist (n = 128); 95 (15%) were initiated on double oral combination therapy and 5 (1%) on triple therapy. After a median treatment time of 4.5 months, there were significant improvements in functional class (p Conclusion Survival of patients with PoPH is strongly associated with the severity of liver disease. Patients who underwent liver transplantation had the best long-term outcomes. Lay summary Portopulmonary hypertension is defined by the presence of pulmonary arterial hypertension in the context of chronic liver disease and is characterized by progressive shortness of breath and exercise limitation. The presence of severe pulmonary arterial hypertension in liver transplant candidates represents a contraindication for such a surgery; however, treatments targeting pulmonary arterial hypertension are efficacious, allowing for safe transplantation and conferring good survival outcomes in those who undergo liver transplantation.

Previous studies have shown that pulmonary hypertension is a predictor of mortality in patients with systolic heart failure (SHF). Persistent pulmonary hypertension after a reactivity test is associated with a worse outcome after transplantation. Recent studies have shown the utility of different haemodynamic parameters.To define best haemodynamic parameters for risk stratification in patients with advanced systolic heart failure.We included 425 consecutive patients who underwent a right heart catheterization with an inotropic challenge if indicated.During a median (interquartile range) follow-up of 1.67 (0.49-4.49) years, there were 151 major cardiac events (126 cardiovascular deaths and 25 postoperative deaths after ventricular assist device implantation or heart transplantation). The most powerful independent predictors of major cardiac events were baseline right atrial pressure (RAP) (hazard ratio [HR]: 1.09, 95% confidence interval [CI]: 1.06-1.12; P0.0001) and baseline pulmonary vascular resistance (PVR) (HR: 1.10; 95% CI: 1.03-1.17; P=0.002). After inotropic challenge, the only independent predictor was mean pulmonary arterial pressure (mPAP) (HR: 1.06; 95% CI: 1.03-1.09; P0.0001). The combination of PVR (≤or3 Wood units), RAP (or≥9mmHg) and mPAP after the inotropic challenge (≤or30mmHg) was the best predictor of major events.We suggest using a simple algorithm based on baseline PVR, baseline RAP and mPAP after the inotropic challenge for the risk stratification of stable patients with advanced systolic heart failure.

Aims Iron deficiency (ID) occurs in about 50% of patients with heart failure (HF). The European Society of Cardiology (ESC) recommends ID diagnostic testing in newly diagnosed patients with HF and during follow‐up, with intravenous iron supplementation (IS) only recommended in patients with HF with reduced ejection fraction (HFrEF). This study aimed to assess prevalence, clinical characteristics, and application of ESC guidelines for ID and IS in patients with HF in the real‐life clinical setting. Methods and results The French transversal multicentre OFICSel registry (300 cardiologists) conducted in 2017 included patients hospitalized for HF at least once in the previous 5 years. Diverse adult patients were eligible including inpatients and outpatients and those with acute and chronic HF. Data were collected from cardiologists and patients using study‐specific surveys. Data included demographic and clinical data, as well as HF and ID management data. Overall, 2822 patients, mainly male (69.3%) with a median age of 69 years (interquartile range 58–78), were included. A total of 1075 patients (38.1%) were tested for ID, with 364 (33.9%) diagnosed. Of these, 168 (46.2%) received IS: 128 (76.2%) intravenous IS and 40 (23.8%) oral. Among the 201 patients with HFrEF diagnosed with ID, 99 (49.3%) received IS: 79 (79.8%) intravenous IS and 20 (20.2%) oral. Conclusions In clinical practice, only one‐third of patients with HF had a diagnostic test for ID. In patients with ID with HFrEF, only 39.3% received intravenous IS as recommended. Thus, in general, cardiologists should be encouraged to follow the ESC guidelines to ensure optimal treatment for patients with HF.

To evaluate the concordance between DECT perfusion and ventilation/perfusion (V/Q) scintigraphy in diagnosing chronic thromboembolic pulmonary hypertension (CTEPH). Eighty patients underwent V/Q scintigraphy and DECT perfusion on a 2nd- and 3rd-generation dual-source CT system. The imaging criteria for diagnosing CTEPH relied on at least one segmental triangular perfusion defect on DECT perfusion studies and V/Q mismatch on scintigraphy examinations. Based on multidisciplinary expert decisions that did not include DECT perfusion, 36 patients were diagnosed with CTEPH and 44 patients with other aetiologies of PH. On DECT perfusion studies, there were 35 true positives, 6 false positives and 1 false negative (sensitivity 0.97, specificity 0.86, PPV 0.85, NPV 0.97). On V/Q scans, there were 35 true positives and 1 false negative (sensitivity 0.97, specificity 1, PPV 1, NPV 0.98). There was excellent agreement between CT perfusion and scintigraphy in diagnosing CTEPH (kappa value 0.80). Combined information from DECT perfusion and CT angiographic images enabled correct reclassification of the 6 false positives and the unique false negative case of DECT perfusion. There is excellent agreement between DECT perfusion and V/Q scintigraphy in diagnosing CTEPH. The diagnostic accuracy of DECT perfusion is reinforced by the morpho-functional analysis of data sets. • Chronic thromboembolic pulmonary hypertension (CTEPH) is potentially curable by surgery. • The triage of patients with pulmonary hypertension currently relies on scintigraphy. • Dual-energy CT (DECT) can provide standard diagnostic information and lung perfusion from a single acquisition. • There is excellent agreement between DECT perfusion and scintigraphy in separating CTEPH and non-CTEPH patients.

Importance Modern data regarding incidence and modes of death of patients with aortic stenosis (AS) are restricted to tertiary centers or studies of aortic valve replacement (AVR). Objective To provide new insights into the natural history of outpatients with native AS based on a large regionwide population study with inclusion by all cardiologists regardless of their mode of practice. Design, Setting, and Participants Between May 2016 and December 2017, consecutive outpatients with mild (peak aortic velocity, 2.5-2.9 m/s), moderate (peak aortic velocity, 3-3.9 m/s), and severe (peak aortic velocity, ≥4 m/s) native AS graded by echocardiography were included by 117 cardiologists from the Nord-Pas-de-Calais region in France. Analysis took place between August and November 2020. Main Outcomes and Measures Natural history, need for AVR, and survival of patients with AS were followed up. Indications for AVR were based on current guideline recommendations. Results Among 2703 patients (mean [SD] age, 76.0 [10.8] years; 1260 [46.6%] women), 233 (8.6%) were recruited in a university public hospital, 757 (28%) in nonuniversity public hospitals, and 1713 (63.4%) by cardiologists working in private practice. A total of 1154 patients (42.7%) had mild, 1122 (41.5%) had moderate, and 427 (15.8%) had severe AS. During a median (interquartile range) of 2.1 (1.4-2.7) years, 634 patients underwent AVR and 448 died prior to AVR. Most deaths were cardiovascular (200 [44.7%]), mainly associated with congestive heart failure (101 [22.6%]) or sudden death (60 [13.4%]). Deaths were noncardiovascular in 186 patients (41.5%) and from unknown causes in 62 patients (13.8%). Compared with patients with mild AS, there was increased cardiovascular mortality in those with moderate (hazard ratio, 1.47 [95% CI, 1.07-2.02]) and severe (hazard ratio, 3.66 [95% CI, 2.52-5.31]) AS. The differences remained significant when adjusted for baseline characteristics or in time-dependent analyses considering AS progression. In asymptomatic patients, moderate and mild AS were associated with similar cardiovascular mortality (hazard ratio, 0.99 [95% CI, 0.44-2.21]). Conclusions and Relevance While patients in this study with moderate AS had a slightly higher risk of cardiovascular death than patients with mild AS, this risk was much lower than that observed in patients with severe AS. Moreover, in asymptomatic patients, moderate and mild AS were associated with similar cardiovascular mortality.

Resume Introduction Aucune donnee n’est disponible concernant la tolerance du bevacizumab, anticorps anti- vascular endothelial growth factor-A (VEGF-A), chez le patient atteint d’hypertension arterielle pulmonaire (HTAP), pathologie dans laquelle le VEGF-A joue un role central et probablement protecteur. Observation Nous rapportons l’observation d’une patiente presentant une HTAP associee a une sclerodermie systemique, stable sous bosentan. La decouverte d’un carcinome epidermoide du col uterin metastatique a conduit a l’administration de deux lignes successives de chimiotherapie cytotoxique. Leur echec a motive l’initiation d’un traitement anti-angiogenique : trois injections de bevacizumab 15 mg/kg ont ainsi ete administrees. Tout au long du traitement, aucune modification clinique ni echographique de l’HTAP n’a ete constatee. Conclusion Cette observation suggere que, sous surveillance clinique et echographique rapprochee, le bevacizumab peut etre bien tolere en cas d’HTAP stable et moderee. La decision de traitement doit etre prise de maniere individuelle et adaptee au rapport benefice–risque, le risque d’aggravation de l’HTAP n’etant pas exclu.

A 72-year-old woman with history of breast cancer only treated surgically was referred to our department for pulmonary hypertension (PH) suspicion. Echocardiogram revealed elevated right ventricular systolic pressure. Computed tomography (CT) angiogram showed no pulmonary embolism (PE), but lung scan revealed two ventilation-perfusion mismatch areas. Right cardiac catheterization established precapillary PH. Despite treatment with PH specific therapy (sildenafil, ambrisentan, and epoprostenol), her condition worsened rapidly with acute right heart failure (RHF). She died 22 days after admission. Post-mortem microscopic examination showed a rare combination of PH etiologies consistent with metastasis of breast cancer in pulmonary vasculature including the rare pulmonary tumour thrombotic microangiopathy (PTTM).

Summary Background Coronary artery disease (CAD) is the leading cause of systolic heart failure (HF). Cardiac magnetic resonance imaging (CMR) is a non-invasive technique that detects a myocardial infarction scar as subendocardial or transmural late gadolinium enhancement (st-LGE). Aim We sought to evaluate whether a lack of st-LGE could rule out CAD in new-onset systolic HF of unknown aetiology. Methods We included 232 consecutive patients with new-onset HF and left ventricular ejection fraction ≤ 35% who underwent both coronary angiography and CMR to assess HF aetiology. CAD was defined as the presence of coronary artery stenosis ≥ 50% on a coronary angiogram. We assessed sensitivity, specificity, and positive and negative likelihood ratios (PLR and NLR) of the presence of st-LGE to detect underlying CAD. A complementary meta-analysis of 11 studies (including ours) was also performed. Results In our study, 49 (21.1%) patients had CAD. The sensitivity and specificity of the presence of st-LGE to detect CAD were 69 and 92%, respectively. PLR and NLR were 8.47 and 0.33, respectively. In the meta-analysis, 1227 patients were included, and the prevalence of CAD ranged from 19.2 to 68.3%. Sensitivity, specificity, PLR and NLR were 87% (95% confidence interval [CI] 0.80–0.92), 93% (95% CI 0.89–0.96), 12.91 (95% CI 7.70–21.64) and 0.14 (95% CI 0.09–0.22), respectively. Altogether, 55 patients presented CAD with no st-LGE; inversely, 75 patients presented st-LGE with no CAD. Conclusion With a CMR specificity of 93%, the absence of st-LGE rules out significant underlying CAD in patients with systolic HF of unknown aetiology in most cases.

Background: Left ventricular remodeling (LVR) after myocardial infarction is associated with an increased risk of heart failure and death. In spite of a modern therapeutic approach, LVR remains relatively frequent and difficult to predict in clinical practice. Our aim was to identify new biomarkers of LVR and understand their involvement in its development. Methods and Results: Proteomic analysis of plasma from the REVE-2 study (Remodelage Ventriculaire)—a study dedicated to the analysis of LVR which included 246 patients after a first anterior myocardial infarction—identified increased plasma levels of CLU (clusterin) in patients with high LVR. We used a rat model of myocardial infarction to analyze CLU expression in the LV and found a significant increase that was correlated with LVR parameters. We found increased CLU expression and secretion in primary cultures of rat neonate cardiomyocytes hypertrophied by isoproterenol. Silencing of CLU in hypertrophied neonate cardiomyocytes induced a significant decrease in cell size, ANP (atrial natriuretic peptide), and BNP (B-type natriuretic peptide) expression, associated with a decreased ERK (extracellular signal-regulated kinase) 1/2 activity, suggesting a prohypertrophic role of CLU. We then confirmed a significant increase of both intracellular p-CLU (precursor form of CLU) and m-CLU (mature form of CLU) in failing human hearts. Finally, the circulating levels of CLU (secreted form) were increased in patients with chronic heart failure who died from cardiovascular cause during a 3-year follow-up (n=99) compared with survivors (n=99). Conclusions: Our results show for the first time that plasma CLU levels are associated with LVR post–myocardial infarction, have in part a cardiac origin, and are a predictor of early death in heart failure patients.

Background Right ventricular (RV) systolic function is a powerful prognostic factor in patients with systolic heart failure. The accurate estimation of RV function remains difficult. The aim of the study was to determine the diagnostic accuracy of 2D-speckle tracking RV strain in patients with systolic heart failure, analyzing both free and posterolateral walls. Methods Seventy-six patients with dilated cardiopathy (left ventricular end-diastolic volume≥75ml/m 2 ) and left ventricular ejection fraction≤45% had an analysis of the RV strain. Feasibility, reproducibility and diagnostic accuracy of RV strain were analyzed and compared to other echocardiographic parameters of RV function. RV dysfunction was defined as a RV ejection fraction≤40% measured by radionuclide angiography. Results RV strain feasibility was 93.9% for the free-wall and 79.8% for the posterolateral wall. RV strain reproducibility was good (intra-observer and inter-observer bias and limits of agreement of 0.16±1.2% [−2.2–2.5] and 0.84±2.4 [−5.5–3.8], respectively). Patients with left heart failure have a RV systolic dysfunction that can be unmasked by advanced echocardiographic imaging: mean RV strain was −21±5.7% in patients without RV dysfunction and −15.8±5.1% in patients with RV dysfunction (p=0.0001). Mean RV strain showed the highest diagnostic accuracy to predict depressed RVEF (area under the curve (AUC) 0.75) with moderate sensitivity (60.5%) but high specificity (87.5%) using a cutoff value of −16%. Conclusions RV strain seems to be a promising and more efficient measure than previous RV echocardiographic parameters for the diagnosis of RV systolic dysfunction.

Background— Some patients with left ventricular systolic dysfunction (LVSD) have a dramatic improvement in left ventricular ejection fraction (LVEF) after β-blockade. No study has analyzed the long-term echocardiographic and clinical follow-up of this subgroup of patients. Methods and Results— We included in this analysis 174 consecutive patients with LVSD who had an LVEF≥45% after β-blockade. We performed a long-term echocardiographic follow-up (median 7.7 [4–9.9] years) and clinical follow-up (median 9.2 [7.2–10.8] years). LVEF improved from 33±8% to 54±6% after β-blockade ( P Conclusions— The long-term survival of patients with LVSD and with near-normal LVEF after β-blockade is good. However, a quarter of these patients may experience a subsequent degradation of LVEF. These patients are at higher risk of cardiovascular mortality.

Background— Extracellular matrix turnover plays a key role in wound repair after myocardial infarction (MI). The aim of the study was to evaluate whether biomarkers of myocardial fibrosis measurements 1 month after MI may predict left ventricular (LV) remodeling. Methods and Results— This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Echocardiographic studies were performed at hospital discharge and 12 months after MI. Brain natriuretic peptide as well as biomarkers of myocardial fibrosis (type 1 collagen telopeptide, aminoterminal propeptide of type I procollagen, aminoterminal propeptide of type III procollagen) were measured 1 month after MI in 218 patients. In multivariate analysis, aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1 (odds ratio [95% confidence interval], 1.86 [1.02–3.39]; P =0.043) 1 month after MI and brain natriuretic peptide >100 pg/mL (2.35 [1.28–4.31]; P =0.006) were associated with a pejorative LV remodeling, whereas LV ejection fraction at discharge (per 5% increment; 0.78 [0.65–0.94]; P =0.01) was independently associated with lower rates of detrimental LV remodeling at 12 months. Patients with high brain natriuretic peptide and aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio ≤1, measured 1 month after MI, had the highest risk of developing a primary composite event (cardiovascular death or hospitalization for worsening heart failure; 14 events per 216 patients; P =0.0001) during a 3-year follow-up. Conclusions— Myocardial fibrosis turnover after MI is associated with LV remodeling. Low aminoterminal propeptide of type III procollagen/type 1 collagen telopeptide ratio (≤1) at 1 month is predictive, in addition to brain natriuretic peptide and LV ejection fraction, of detrimental LV remodeling as well as cardiovascular deaths and hospitalizations for heart failure.

A 72‐year‐old woman with history of breast cancer only treated surgically was referred to our department for pulmonary hypertension (PH) suspicion. Echocardiogram revealed elevated right ventricular systolic pressure. Computed tomography (CT) angiogram showed no pulmonary embolism (PE), but lung scan revealed two ventilation‐perfusion mismatch areas. Right cardiac catheterization established precapillary PH. Despite treatment with PH specific therapy (sildenafil, ambrisentan, and epoprostenol), her condition worsened rapidly with acute right heart failure (RHF). She died 22 days after admission. Post‐mortem microscopic examination showed a rare combination of PH etiologies consistent with metastasis of breast cancer in pulmonary vasculature including the rare pulmonary tumour thrombotic microangiopathy (PTTM).

Heart failure (HF) remains a severe disease with a poor prognosis. HF biomarkers may include demographic features, cardiac imaging, or genetic polymorphisms but this term is commonly applied to circulating serum or plasma analytes. Biomarkers may have at least three clinical uses in the context of HF: diagnosis, risk stratification, and guidance in the selection of therapy. Proteomic studies on HF biomarkers can be designed as case/control using clinical endpoints; alternatively, left ventricular remodeling can be used as a surrogate endpoint. The type of samples (tissue, cells, serum or plasma) used for proteomic analysis is a key factor in the research of biomarkers. Since the final aim is the discovery of circulating biomarkers, and since plasma and serum samples are easily accessible, proteomic analysis is frequently used for blood samples. However, standardization of sampling and access to low-abundance proteins remains problematic. Although, proteomics is playing a major role in the discovery phase of biomarkers, validation in independent populations is necessary by using more specific methods. The knowledge of new HF biomarkers may allow a more personalized medicine in the future.

Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death. However, LV remodeling is difficult to predict, and limited information is available on the association of cardiac biomarkers with LV remodeling. Our aim was to study the association of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI), and C-reactive protein with LV remodeling after MI. We designed a prospective multicenter study including 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 months and 1 year after MI; quantitative analysis was performed at a core echocardiographic laboratory. Blood samples for determination of BNP, cTnI, and C-reactive protein levels were obtained at hospital discharge and the 1-month, 3-month, and 1-year follow up visits. One-year echocardiographic follow-up was obtained in 226 patients. End-diastolic volume increased from 52.3 ± 13.8 ml/m(2) at baseline to 62.3 ± 18.4 ml/m(2) at 1 year (p0.0001); LV remodeling (20% increase in end-diastolic volume) was observed in 87 patients (38%). At baseline, we found significant univariate relations between LV remodeling and the 3 biomarkers. During follow-up, high BNP levels and persistently detectable levels of cTnI were associated with LV remodeling. In multivariate analysis, none of the 3 biomarkers at baseline was independently predictive of LV remodeling. In contrast, during follow-up, high BNP and positive cTnI were independently associated with LV remodeling. In conclusion, circulating cardiac biomarkers may reflect pathophysiologic processes implicated in LV remodeling after MI. Determination of BNP and cTnI during follow-up can help refine risk stratification.

Purpose: Depletion of major blood proteins is one of the most promising approaches to accessing low abundance biomarkers for proteomics studies. The use of combinatorial peptide ligand library (CPLL) for accessing these low abundance proteins in plasma from patients with a myocardial infarction (MI) was tested to identify candidate protein biomarkers of left ventricular remodeling (LVR). Experimental design: Serial blood samples of MI patients followed for one year (at inclusion, 1 month, 3 months, and 1 year) were treated with CPLL and analyzed by SELDI-TOF-MS. Result: The use of CPLL increased resolution, with loss of most abundant plasma proteins, reproducibly and improved the intensity of low-abundance proteins. Longitudinal information allowed us to reduce by 55% the final number of peaks identified as significantly modulated throughout the 1-year follow-up after MI. Interestingly, 19 of the 26 peaks finally selected were detected only in samples treated from CPLL. The 2777 m/z peak, found in less elevated level in high remodeling patients, was identified as being DAHKSEVAHR FKDLGEENFKALVL, the N-terminal peptide (24–48 aa) generated from albumin by pepsin cleavage. Conclusions and clinical relevance: This finding shows the potential of CPLL in accessing low-abundance proteins to select and identify candidate biomarkers in patients with LVR.

a Clinique de cardiologie, Pole Cardio-vasculaire et Pulmonaire, Centre Hospitalier Regional et Universitaire de Lille, Lille, France b Universite de Lille 2, Lille, France c Inserm U744, Institut Pasteur de Lille, Universite de Lille 2, Lille, France d Service d'explorations fonctionnelles cardio-vasculaires, Pole d'imagerie, Centre Hospitalier Regional et Universitaire de Lille, Lille, France e Service de Chirurgie cardio-vasculaire, Pole Cardio-Vasculaire et Pulmonaire, Centre Hospitalier Regional et Universitaire de Lille, Lille, France

This study aims to study the clinical implications of the concomitant use of a left ventricular assist device (LVAD) and an implantable cardioverter-defibrillator (ICD). In this retrospective study, all patients who underwent LVAD (Heart Mate II) implantation with concomitant ICD therapy at our institution between June 2007 and August 2012 were included. We sought to investigate (1) the electromagnetic interference between LVAD and ICD telemetry, (2) the effect of LVAD implantation on right ventricular (RV) lead parameters and (3) the ventricular tachyarrhythmias (VAs) that occur post-LVAD implantation. Of the 23 patients (53 ± 9 years, 73 % male, LVEF 19 ± 9 %) included, ICD telemetry was lost in four patients post-LVAD implantation (Saint-Jude-Medical Atlas V-193, V-240, V-243, and Sorin CRT-8750), prompting either use of a metal shield (n = 1), a change in position of the programmer head (n = 1) or ICD replacement (n = 2). LVAD implantation was associated with a decrease in both RV signal amplitude (p = 0.04) and RV impedance (p

ObjectiveLeft ventricular (LV) remodeling following myocardial infarction (MI) is characterized by progressive alterations of structure and function, named LV remodeling. Although several risk factors such as infarct size have been identified, LV remodeling remains difficult to predict in clinical practice. Changes within the extracellular matrix, involving matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs), are an integral part of left ventricular (LV) remodeling after myocardial infarction (MI). We investigated the temporal profile of circulating MMPs and TIMPs and their relations with LV remodeling at 1 year and clinical outcome at 3 years in post-MI patients.MethodsThis prospective multicentre study included 246 patients with a first anterior MI. Serial echocardiographic studies were performed at hospital discharge, 3 months, and 1 year after MI, and analysed at a core laboratory. LV remodeling was defined as the percent change in LV end-diastolic volume (EDV) from baseline to 1 year. Serum samples were obtained at hospital discharge, 1, 3, and 12 months. Multiplex technology was used for analysis of MMP-1, -2, -3, -8, -9, -13, and TIMP-1, -2, -3, -4 serum levels.ResultsBaseline levels of MMP-8 and MMP-9 were positively associated with changes in LVEDV (P = 0.01 and 0.02, respectively). When adjusted for major baseline characteristics, MMP-8 levels remained an independent predictor LV remodeling (P = 0.025). By univariate analysis, there were positive relations between cardiovascular death or hospitalization for heart failure during the 3-year follow-up and the baseline levels of MMP-2 (P = 0.03), MMP-8 (P = 0.002), and MMP-9 (P = 0.03). By multivariate analysis, MMP-8 was the only MMP remaining significantly associated with clinical outcome (P = 0.02).ConclusionBaseline serum MMP-8 is a significant predictor of LV remodeling and cardiovascular outcome after MI and may help to improve risk stratification.

Aims Previous studies have demonstrated that the radionuclide right ventricular (RV) ejection fraction (RVEF), tricuspid annular plane systolic excursion (TAPSE), and tissue Doppler peak systolic tricuspid annular velocity (STr) were independent predictors of cardiac survival in stable patients with left ventricular systolic dysfunction (LVSD). No study has compared the prognostic value of these three RV parameters. The aim of this study was to compare the prognostic value of RVEF, TAPSE, and STr in a large group of patients with LVSD. Methods and results We analysed 527 consecutive patients who underwent an extensive prognostic evaluation (clinical data, biological data, radionuclide angiography, echoDopplercardiography, cardiopulmonary exercise test). Tricuspid annular plane systolic excursion and STr were weakly correlated with RVEF (r = 0.20). During a follow-up period of 1268 days (802-1830), there were 121 cardiovascular deaths. Best cut-off values were 37%, 9.7 cm/s, and 18.5 mm for RVEF, STr, and TAPSE, respectively. Right ventricular ejection fraction was a powerful independent predictor of cardiac survival [relative risk (RR): 2.05 (1.29-3.26), P = 0.002]. Peak systolic tricuspid annular velocity added a modest prognostic information [RR: 1.56 (1.02-2.39), P = 0.04]. However, the combination of STr with RVEF was the most powerful predictor of cardiovascular death. Tricuspid annular plane systolic excursion was not an independent predictor of cardiac survival. Conclusions Right ventricular systolic function remains a powerful independent predictor of the clinical outcome. Even in the context of a complete echocardiographic assessment, radionuclide RVEF continues to be the most powerful RV systolic parameter for cardiac survival prediction. However, the determination of STr, in addition to RVEF, could improve risk stratification.

Left ventricular (LV) remodeling after myocardial infarction (MI) indicates a high risk of heart failure and death, but LV remodeling remains difficult to predict. Biomarkers may help to refine risk stratification for a more personalized medical approach. They may also shed light on the pathophysiologic processes involved. We performed a systematic review of the published evidence about the association of circulating biomarkers with LV remodeling after MI. We selected 59 publications. Overall, these studies examined 112 relations between 52 different biomarkers and LV remodeling. The biomarkers most consistently associated with LV remodeling were involved in extracellular matrix turnover or neurohormonal activation: matrix metalloproteinase-9, collagen peptides, and B-type natriuretic peptide. This review underscores the vitality of the research on LV remodeling but concludes that the ideal biomarker has not yet been identified. To reach this goal, future studies will have to be larger, have standardized imaging end points, and include replication populations to define optimal cutoffs for LV remodeling prediction. Cardiovascular magnetic resonance appears to be the best technique for LV remodeling assessment but its current availability may be a concern for recruitment for multicenter studies. Recent technologic advances will probably yield new candidate biomarkers of LV remodeling. Tests are necessary to determine whether a multimarker approach would significantly improve risk prediction.

Summary Background Apoptosis-related molecules may contribute to left ventricular (LV) remodeling after myocardial infarction (MI). To validate this hypothesis, we evaluated the relation between circulating plasma levels of soluble Fas ligand (sFas-L) and LV remodeling in patients post-MI. Methods and results This prospective multicenter study included 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 and 12 months after MI; quantitative analysis was performed at a core echocardiography laboratory. Clinical follow-up was performed at 3 years post-MI. Blood samples to measure sFas-L were obtained at 1 month after MI. Median sFas-L level was 50.2 pg/mL. During the 1 year follow-up, LV remodeling was documented by a significant increase in LV volumes. LV end-diastolic and end-systolic volumes at baseline, 3 months, and 12 months after MI did not differ according to sFas-L levels; changes in LV volumes were not associated with sFas-L levels. By multivariate analysis, 2 variables were independently associated with LV remodeling: B-type natriuretic peptide (BNP) ( p = 0.008) and baseline ejection fraction ( p = 0.02). sFas-L levels were not associated with cardiovascular death or rehospitalization for heart failure at 3 years; conversely, high levels of BNP were associated with worse clinical outcome. Conclusions Soluble Fas-L levels are not associated with LV remodeling after MI. Further research is needed to identify apoptotic markers that may be associated with outcome post-MI.

Aim As experimental studies suggest that hepatocyte growth factor (HGF) is cardioprotective after myocardial infarction (MI), this study sought to investigate relationships between circulating levels of HGF and left ventricular (LV) remodelling in patients after acute MI. Methods and results This prospective multicentre study included 246 patients with a first anterior Q-wave MI. Serial echocardiographic studies were performed at hospital discharge and 3 and 12 months after MI; quantitative analysis was performed at a core echocardiography laboratory. Blood samples to measure HGF, brain natriuretic peptide (BNP), and C-reactive protein were obtained at discharge and at the 1, 3, and 12 month follow-up visits. Plasma HGF levels were high at baseline, decreased at 1 month, and remained stable thereafter. In the post-MI period (at 3 and 12 months), HGF levels were positively associated with LV volumes, wall motion systolic index, E/Ea, and BNP; and negatively with LV ejection fraction. High HGF levels were associated with higher C-reactive protein levels. Multivariate analysis showed that both BNP (P < 0.0001) and C-reactive protein (P < 0.0001) were independently associated with HGF levels at 3 and 12 months. Patients who died or were rehospitalized for heart failure during follow-up had higher HGF levels at 1 month (P = 0.0006), 3 months (P = 0.018), and 1 year (P = 0.006) after MI. Conclusions Circulating HGF levels correlate with all markers of LV remodelling after MI and are associated with rehospitalization for heart failure.

Analysis by SELDI-TOF-MS of low abundance proteins makes it possible to select peaks as candidate biomarkers. Our aim was to define a purification strategy to optimise identification by MS of peaks detected by SELDI-TOF-MS from plasma or serum, regardless of any treatment by a combinatorial peptide ligand library (CPLL). We describe 2 principal steps in purification. First, choosing the appropriate sample containing the selected peak requires setting up a databank that records all the m/z peaks detected from samples in different conditions. Second, the specific purification process must be chosen: separation was achieved with either chromatographic columns or liquid-phase isoelectric focusing, both combined when appropriate with reverse-phase chromatography. After purification, peaks were separated by gel electrophoresis and the candidate proteins were analyzed by nano-liquid-chromatography-MS/MS. We chose 4m/z peaks (9400, 13,571, 13,800 and 15,557) selected for their differential expression between two conditions, as examples to explain the different strategies of purification, and we successfully identified 3 of them. Despite some limitations, our strategy to purify and identify peaks selected from SELDI-TOF-MS analysis was effective.

SummaryBackgroundLeft ventricular systolic function is a useful indicator of in-hospital prognosis in patients with acute myocardial infarction. For long-term risk stratification, however, the variable degree of recovery that may occur during the ensuing period has also to be taken into account.AimsTo analyse the prevalence, time course, determinants and correlates of late left ventricular function recovery after myocardial infarction, from hospital discharge to 1-year follow-up, using systematic serial assessment of left ventricular function.MethodsData from 512 patients with a first anterior myocardial infarction included in two prospective studies on left ventricular remodelling (REVE and REVE-2) were analysed. Serial echocardiographic studies were performed before discharge, at 3 months and at 1 year after myocardial infarction. Left ventricular volumes, ejection fraction, and Wall Motion Score Index were determined at a core echocardiographic laboratory.ResultsIn both cohorts, there was a significant decrease in Wall Motion Score Index between discharge and 1 year (from 1.87±0.15 to 1.71±0.21 [P

Echinococcosis is endemic in sheep- and cattle-raising areas in Europe, especially in Southern and Central Europe. In France, most cases originated from immigrants from countries where echinococcosis is endemic. Extremely rare native cases have been reported during the last few years in France, especially those concerning isolated cardiac hydatid cyst. In this case report, we propose a complete imaging description of the features of a typical cardiac hydatid cyst from cardiac MRI, complete with surgery, parasitology, and anatomopathology images.

Depletion of major blood proteins is one of the most promising approaches to accessing low-abundance biomarkers. This study compared the use of combinatorial peptide ligand library (CPLL) and albumin and immunoglobulins (IgGs) depletion technology for accessing these low-abundance proteins in plasma using 2-DE in an acidic restricted pH range (4-7). Compared with native plasma, both techniques enlarge the visibility of other proteins than albumin and IgG, but there were marked differences in their composition. An increase of the number of spots was detected compared with native plasma (157 spots) with 427 and 557 spots, respectively, detected with albumin and IgG depletion, and CPLL treatment. We selected 70 spots to be identified by MALDI-TOF related to their absence in the 2-D gels from native or albumin and IgG-depleted plasma. The 42 spots identified corresponded to 24 different proteins, with more than half of the proteins which did not belong to the major plasma proteins. CPLL treatment allowed the accessibility to proteolytic fragments obtained from major plasma proteins. We found a large superiority of the CPLL approach over the albumin and IgG depletion process. These findings show the utility of depleting major blood proteins to be able to access low-abundance proteins and the potential of CPLL to select and identify candidate biomarkers in clinical studies.

SummaryBackgroundLeft atrial (LA) volume is an important predictor of mortality and morbidity after myocardial infarction (MI). However, the process of LA remodelling has not been extensively investigated.AimsOur purpose was to analyse the incidence, determinants and consequences of LA remodelling in a cohort of patients with a first anterior MI enrolled in the modern era of MI management.MethodsWe used data from 246 patients with a first anterior MI who were included in a prospective study on left ventricular (LV) remodelling (REVE-2). Serial echocardiographic studies were performed before discharge and at 3 months and 1 year after MI.ResultsLA volume increased from 20.5±5.9mL/m2 at baseline to 24.6±7.4mL/m2 at 3 months (P

Background Severe pulmonary hypertension is a usual contraindication to heart transplantation. A few studies have found that sildenafil has a favourable effect on haemodynamic variables in patients with severe left ventricular systolic dysfunction. Aim To report our clinical experience of sildenafil in patients with left ventricular systolic dysfunction and severe pulmonary hypertension. Methods All patients underwent echocardiography, radionuclide angiography, a cardiopulmonary exercise test and right heart catheterization before and after treatment with sildenafil. All patients were clinically stable and were receiving maximal tolerated doses of recommended drugs. Results We included 18 patients, with a mean ± standard deviation age of 47 ± 13 years. After a median of 8.7 months (interquartile range, 4.4–13.5 months) on sildenafil, there was a significant improvement in New York Heart Association classification (P = 0.02) and mean right ventricular ejection fraction (from 26 ± 7% to 30 ± 9%; P = 0.008), with a decrease in the VE/VCO2 slope (from 52 ± 11 to 44 ± 11; P = 0.009) and in pulmonary vascular resistance (from 5.3 ± 1.9 Wood units to 3.3 ± 1.8 Wood units; P = 0.01). During follow-up, three patients had urgent heart transplantation, two had non-urgent transplantation and six had left ventricular assist device implantation. All patients with pulmonary vascular resistance

Aims Evaluate the factors presents at diagnosis associated to left ventricular recovery in acute heart failure (AHF) revealing reduced left ventricular ejection fraction (LVEF). Background A lot of paperwork have studied the left ventricular evolution in chronic heart failure but not in AHF and indistinctly of LVEF. We don’t know the predictive factors of left ventricular recovery in a specific population of acute heart failure revealing reduced LVEF. Methods We conducted a prospective and observational longitudinal study with retrospective data collection based on a cohort of patients with acute heart failure revealing reduced LVEF (≤45%), in the emergency department and cardiac intensive care unit (ED and CCIU) of the University Hospital of Lille, between November 1st, 2011 and May 31st, 2013. The primary endpoint was the improvement of LVEF or left ventricular reverse remodeling. Results Among the 111 patients included, 57% of patients benefited from an improvement of LVEF and 62% from a reverse remodeling in the 51% of patients with a dilated left ventricle. The improvement of LVEF was associated in univariate analysis to non ischaemic etiology (p=0.002) and greater utilization of betablockers (p=0.076) and angiotensin-converting enzyme (p=0.0337) and in multivariate analysis, independtly to younger patients (p=0.0325) and presentation by cardiogenic shock (p=0.0484). The same predictive factors were found for reverse remodeling. Conclusion The knowledge of the prevalence and the early predictive factors of the left ventricular recovery can be useful to guide the follow-up and non-pharmacological management of heart failure with reduced LVEF.

BackgroundRisk stratification of patients with stable chronic heart failure (CHF) is critical to better identify those who may benefit the most from invasive strategies such as heart transplantation.MethodsTo improve cardiovascular (CV) death prediction in CHF, we performed a proteomic analysis using high throughput surface enhanced laser desorption ionization – time of fight – mass spectrometry (SELDI-TOF-MS). Plasma samples were pre-treated to access the deep proteome. The proteomic analysis was first performed in a case (CV death within 3 years) /control (survivors at 3 years) study including 198 patients with a left ventricular ejection fraction (LVEF)

ContexteLe remodelage ventriculaire gauche (VG) est le mécanisme physiopathologique le plus fréquemment observé dans les cas d’insuffisance cardiaque (IC) après un infarctus du myocarde (IDM). Notre travail a porté sur la recherche de nouveaux marqueurs circulants du remodelage VG en post-infarctus par analyse protéomique différentielle.Matériel et Méthodes45 patients, ayant présenté un IDM antérieur inaugural, inclus dans une étude prospective, ont été étudiés. Ils ont bénéficié d’un prélèvement sanguin veineux (à l’inclusion, à 1 mois, 3 mois et 1 an). La population a été divisée en 3 groupes selon les tertiles de remodelage VG, définis par échocardiographie. L’analyse protéomique s’est centrée sur les protéines minoritaires ou « deep proteome » : nous avons traité l’ensemble des échantillons sanguins (180 de plasma et 180 de sérum) par une technique d’équalisation (figure 1) permettant de comprimer la gamme dynamique de concentration des protéines. Nous les avons ensuite analysés par SELDI TOF MS (Surface Enhanced Laser Desorption/Ionization Time Of Flight Mass Spectrometry) à l’aide de 5 types de barrettes (Q10, CM10, H50, IMAC Cuivre et IMAC Nickel).RésultatsEn comparant les profils protéiques du groupe sans remodelage VG au groupe de remodelage élevé, à chacun des 4 temps de l’étude, nous avons trouvé 51 pics différentiellement exprimés (p