Phase 1 Trial of Antibody NI006 for Depletion of Cardiac Transthyretin Amyloid.

BACKGROUND: Transthyretin amyloid (ATTR) cardiomyopathy is a progressive and fatal disease caused by misfolded transthyretin. Despite advances in slowing disease progression, there is no available treatment that depletes ATTR from the heart for the amelioration of cardiac dysfunction. NI006 is a recombinant human anti-ATTR antibody that was developed for the removal of ATTR by phagocytic immune cells. METHODS: In this phase 1, double-blind trial, we randomly assigned (in a 2:1 ratio) 40 patients with wild-type or variant ATTR cardiomyopathy and chronic heart failure to receive intravenous infusions of either NI006 or placebo every 4 weeks for 4 months. Patients were sequentially enrolled in six cohorts that received ascending doses (ranging from 0.3 to 60 mg per kilogram of body weight). After four infusions, patients were enrolled in an open-label extension phase in which they received eight infusions of NI006 with stepwise increases in the dose. The safety and pharmacokinetic profiles of NI006 were assessed, and cardiac imaging studies were performed. RESULTS: The use of NI006 was associated with no apparent drug-related serious adverse events. The pharmacokinetic profile of NI006 was consistent with that of an IgG antibody, and no antidrug antibodies were detected. At doses of at least 10 mg per kilogram, cardiac tracer uptake on scintigraphy and extracellular volume on cardiac magnetic resonance imaging, both of which are imaging-based surrogate markers of cardiac amyloid load, appeared to be reduced over a period of 12 months. The median N-terminal pro-B-type natriuretic peptide and troponin T levels also seemed to be reduced. CONCLUSIONS: In this phase 1 trial of the recombinant human antibody NI006 for the treatment of patients with ATTR cardiomyopathy and heart failure, the use of NI006 was associated with no apparent drug-related serious adverse events. (Funded by Neurimmune; NI006-101 ClinicalTrials.gov number, NCT04360434.).

Phase analysis for ventricular arrhythmia prediction: A retrospective monocentric cohort study.

BACKGROUND: Prediction of ventricular arrhythmias (VA) mostly relies on left ventricular ejection fraction (LVEF), but with limited performance. New echocardiographic parameters such as mechanical dispersion have emerged, but acoustic window sometimes precludes this measurement. Nuclear imaging may be an alternative. We aimed to assess the ability of mechanical dispersion, measured with phase standard deviation (PSD) on radionuclide angiocardiography (RNA), to predict VAs. METHODS: This retrospective monocentric observational study included all patients who underwent a tomographic RNA from 2015 to 2019. Phase analysis yielded PSD and follow-up was examined to identify VAs, heart transplantation, and death. RESULTS: The study population consisted of 937 patients, mainly with LVEF ≤ 35% (425, 45%). Most had ischemic (334, 36%) or dilated cardiomyopathies (245, 26%). We identified 86 (9%) VAs. PSD was strongly associated with the occurrence of VA [hazard ratio per 10 ms increase (HR10) 1.12 (1.09-1.16)], heart transplantation [HR10 1.09 (1.06-1.12)], and death [HR10 1.03 (1.00-1.05)]. The association between PSD and VA persisted after adjustment for age, sex, QRS duration, LVEF, global longitudinal strain (GLS), and echocardiography-assessed mechanical dispersion. CONCLUSION: The occurrence of ventricular arrhythmias was predicted by mechanical dispersion assessed by RNA, even after adjustment for LVEF and GLS.

Retrospective Study of 573 Patients with Heart Failure Evaluated for Coronary Artery Disease at Toulouse University Center, France.

BACKGROUND Heart failure (HF) most commonly occurs due to ischemic heart disease from stenotic coronary artery disease (CAD). HF is classified into 3 groups based on the percentage of the ejection fraction (EF): reduced (HFrEF), mid-range (HFmrEF), and preserved (HFpEF). This retrospective study included 573 patients who presented with HF based on the evaluation of EF and were evaluated for CAD by coronary angiography before undergoing coronary angioplasty at a single center in Toulouse, France. MATERIAL AND METHODS This retrospective observational study included patients recently diagnosed with HF or acute decompensation of chronic HF and referred for coronary angiography at Toulouse University Hospital between January 2019 and May 2020. RESULTS Significant CAD was found in 55.8%, 55%, and 55% of the whole population, HFpEF, and HFrEF groups, respectively. Older age, male sex, and diabetes mellitus were the main risk factors for ischemic HF. Except for age and sex, patients with ischemic HFpEF were comparable to those with non-ischemic HFpEF, unlike the ischemic HFrEF group, which had more common cardiovascular risk factors than the non-ischemic HFrEF group. The ischemic HFpEF group had an older age and higher rate of dyslipidemia than the ischemic HFrEF group. CONCLUSIONS At our center, CAD was diagnosed in more than half of patients who presented with heart failure with preserved or reduced EF. Older age and male sex were the common risk factors in patients with HFpEF and HFrEF.

Intraventricular Thrombus Formation and Embolism in Takotsubo Syndrome: Insights From the International Takotsubo Registry.

OBJECTIVE: Takotsubo syndrome (TTS) is characterized by acute left ventricular dysfunction, which can contribute to intraventricular thrombus and embolism. Still, prevalence and clinical impact of thrombus formation and embolic events on outcome of TTS patients remain unclear. This study aimed to investigate clinical features and outcomes of patients with and without intraventricular thrombus or embolism. Additionally, factors associated with thrombus formation or embolism, as well as predictors for mortality, were identified. Approach and Results: TTS patients enrolled in the International Takotsubo Registry at 28 centers in Australia, Europe, and the United States were dichotomized according to the occurrence/absence of intraventricular thrombus or embolism. Patients with intraventricular thrombus or embolism were defined as the ThrombEmb group. Of 1676 TTS patients, 56 (3.3%) patients developed intraventricular thrombus and/or embolism following TTS diagnosis (median time interval, 2.0 days [range, 0-38 days]). Patients in the ThrombEmb group had a different clinical profile including lower left ventricular ejection fraction, higher prevalence of the apical type, elevated levels of troponin and inflammatory markers, and higher prevalence of vascular disease. In a Firth bias-reduced penalized-likelihood logistic regression model apical type, left ventricular ejection fraction ≤30%, previous vascular disease, and a white blood cell count on admission >10×103 cells/µL emerged as independent predictors for thrombus formation or embolism. CONCLUSIONS: Intraventricular thrombus or embolism occur in 3.3% of patients in the acute phase of TTS. A simple risk score including clinical parameters associated with intraventricular thrombus formation or embolism identifies patients at increased risk. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT01947621.

Prevalence of malnutrition in coronavirus disease 19: the NUTRICOV study.

Recent European Society of Parenteral and Enteral Nutrition guidelines highlighted the interest of prevention, diagnosis and treatment of malnutrition in the management of coronavirus disease 19 (COVID-19) patients. The aim of our study was to evaluate the prevalence of malnutrition in patients hospitalised for COVID-19. In a prospective observational cohort study malnutrition was diagnosed according to the Global Leadership Initiative on Malnutrition (GLIM) two-step approach. Patients were divided into two groups according to the diagnosis of malnutrition. Covariate selection for the multivariate analysis was based on P <0·2 in univariate analysis, with a logistic regression model and a backward elimination procedure. A partitioning of the population was realised. Eighty patients were prospectively enrolled. Thirty patients (37·5 %) had criteria for malnutrition. The need for intensive care unit admission (n 46, 57·5 %) was similar in the two groups. Three patients who died (3·75 %) were malnourished. Multivariate analysis exhibited that low BMI (OR 0·83, 95 % CI 0·73, 0·96, P = 0·0083), dyslipidaemia (OR 29·45, 95 % CI 3·12, 277·73, P = 0·0031), oral intake reduction <50 % (OR 3·169, 95 % CI 1·04, 9·64, P = 0·0422) and glomerular filtration rate (Chronic Kidney Disease Epidemiology Collaboration; CKD-EPI) at admission (OR 0·979, 95 % CI 0·96, 0·998, P = 0·0297) were associated with the occurrence of malnutrition. We demonstrate the existence of a high prevalence of malnutrition in a general cohort of COVID-19 inpatients according to GLIM criteria. Nutritional support in COVID-19 care seems an essential element.

Quantitative assessment of tricuspid regurgitation using right and left ventricular stroke volumes obtained from tomographic equilibrium radionuclide ventriculography.

BACKGROUND: Quantitative assessment of valve regurgitation using volumetric method by comparing right and left ventricular stroke volumes is still under investigations. AIMS: To investigate the accuracy of tomographic equilibrium radionuclide ventriculography (t-ERV) for the quantification of tricuspid regurgitation (TR). METHODS AND RESULTS: Sixty-one patients (44 men; mean age 59 ± 12 years) who underwent both t-ERV and transthoracic echocardiography (TTE) studies within 2 weeks for right ventricular systolic function assessment were eligible for inclusion. A sub-group of 22 patients underwent both t-ERV and CMR. Patients with mitral/aortic regurgitation by TTE were excluded of the study. TR regurgitant volume (RVol) was calculated using the proximal isovelocity surface area (PISA) method from TTE and the volumetric method (right ventricular stroke volume minus left ventricular stroke volume) from t-ERV. There was a significant correlation between RVol as assess by ERV and by TTE (R = 0.95, P < 0.0001). Intraclass correlation coefficient between TTE and ERV for TR quantification was 0.95 (P < 0.0001). Among patients who underwent CMR, the correlation between RVol obtained by TTE and by t-ERV and CMR were R = 0.81 and R = 0.75, respectively (all P < 0.0001). CONCLUSION: TR assessment using the t-ERV correlates well with PISA from TTE in patients referred for right ventricular systolic function assessment.

Value of Longitudinal Strain to Identify Wild-Type Transthyretin Amyloidosis in Patients With Aortic Stenosis.

BACKGROUND: Wild-type transthyretin-related amyloidosis (ATTRwt) and degenerative aortic stenosis (AS) are both age-related. Diagnosis of cardiac amyloidosis (CA) among patients with AS may be difficult due to overlapping morphological and functional criteria. The aim of this study was to describe an echocardiographic longitudinal strain (LS) pattern among patients with AS with and without ATTRwt.Methods and Results:Patients who have AS with ATTRwt (n=30), AS without ATTRwt (n=50) and ATTRwt without AS (n=31) underwent two-dimensional speckle-tracking echocardiography. Transthyretin CA was based on positive bone scintigraphy without monoclonal gammopathy. All patients showed a gradual decrease in LS from the base to the apex resulting in a decrease of the global LS. A cut-off value of 1.0 for relative apical LS (average apical LS/[average basal LS+mid-LS]) was sensitive (88%) but less specific (68%) in differentiating ATTRwt among patients with severe AS. The best cut-off value for relative apical LS for identifying patients with ATTRwt among the whole population was 0.9 (sensitivity 74%, specificity 66%); however, 35%, 25% and 11% of patients who have ATTRwt without AS, with moderate AS and with severe AS, respectively, did not reach this threshold. CONCLUSIONS: A decrease of global and relative apical LS is common in patients with AS, even in the absence of ATTRwt. ATTRwt CA can be present even in the absence of relative apical sparing of LS.

Nonculprit Artery Myocardial Infarction and Complex Coronary Lesions in Anterior ST-Elevated Myocardial Infarction Patients: Data from the CIRCUS Study.

AIMS: Periprocedural myocardial infarctions have been reported in the setting of planned percutaneous coronary intervention (PCI). We assessed the prevalence of nonculprit artery acute myocardial infarction (NCAMI) and its relationship with coronary artery characteristics, final infarct size, and 1-year adverse clinical outcomes in a population of anterior ST-elevated myocardial infarction (STEMI) patients. METHODS AND RESULTS: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) studies were performed within 7 days of admission in 129 anterior STEMI patients from the CIRCUS trial treated by primary PCI. Infarct in the noninfarct artery territory (circumflex, right coronary) was assessed on LGE-CMR and T2-weighted images. Eleven (8.5%) patients exhibited NCAMI. The only independent characteristic significantly associated with NCAMI was the presence of multiple complex coronary lesions (odds ratio = 12.9, 95% confidence interval [3.1-53.4]; p < 0.001). There was a significantly increased infarct size in NCAMI patients compared to patients without NCAMI (45.8 ± 20.4% of the left ventricle [LV] vs. 31.0 ± 15.1% of LV, respectively; p = 0.02), with lower LV ejection fraction (46 ± 10% vs. 34 ± 8%, respectively; p < 0.001). CONCLUSION: NCAMIs are present in 8.5% of anterior STEMI patients and are significantly associated with multiple complex coronary lesions without significant relationship to any revascularization procedural technique. NCAMI was associated with a greater infarct size and reduced LVEF but not worse clinical outcomes at 1 year.

Evaluation of Mitral and Aortic Valvular Disease and Left Ventricular Dysfunction in a Lebanese Population: Retrospective Single-Center Experience.

BACKGROUND Recently, new therapeutic approaches have revolutionized the management of left ventricular dysfunction (LVD) and valvular heart disease (VHD), which are a growing public health problem. In parallel, there are no available epidemiological data about LVD and VHD in developing countries, especially in the Mediterranean area. This retrospective study was conducted at a single center and aimed to evaluate the associations between mitral and aortic valvular disease and left ventricle systolic and diastolic dysfunction in the Lebanese population. MATERIAL AND METHODS A retrospective study was conducted of 4520 consecutive patients aged >18 years who were referred to the Cardiovascular Department of Notre Dame de Secours-University Hospital in Jbeil-Lebanon for transthoracic echocardiography between December 2016 and December 2019. The study population was divided into different groups based on types of LVD and VHD. Left ventricle systolic dysfunction was defined as a left ventricle ejection fraction (EF) ≤40%. Statistical analysis was carried out using SPSS software version 20. RESULTS VHD and systolic dysfunction were more common in men, whereas diastolic dysfunction was more common in women. Being older than age 65 years and smoking were significantly associated with heart failure with preserved EF, whereas female sex was a significant preventive factor against heart failure with reduced EF. Systemic hypertension was correlated with mitral stenosis and tricuspid regurgitation, whereas diabetes mellitus was associated with tricuspid regurgitation (TR). Smoking and older age also appeared to be associated with aortic stenosis. CONCLUSIONS Mitral valve disease (regurgitation and stenosis) was significantly correlated with systolic dysfunction, whereas aortic and mitral regurgitation were associated with diastolic dysfunction. Better monitoring of cardiovascular disease risk factors may lead to a reduced burden of LVD and VHD.

Severe mitral regurgitation recurrence after successful percutaneous mitral edge-to-edge repair by Mitraclip in primary mitral regurgitation: Insights from a three-dimensional echocardiography study.

BACKGROUND: The sustainability of the results of Mitraclip procedures is a source of concern. AIMS: To investigate risk factors of severe mitral regurgitation (MR) recurrence after Mitraclip in primary MR. METHODS AND RESULTS: Eighty-three patients undergoing successful Mitraclip procedures were retrospectively included. Valve anatomy and Mitraclips placement were comprehensively analyzed by post-processing 3D echocardiographic acquisition. The primary composite endpoint was the recurrence of severe MR. The average age was 83±7 years-old, 37 (44%) were female. Median follow-up was 381 days (IQR 195-717) and 17 (20%) patients reached the primary endpoint. Main causes of recurrence of severe MR were relapse of a prolapse (64%) and single leaflet detachment (23%). Posterior coaptation line length (HR 1.06 95%CI 1.01-1.12 p = 0.02), poor imaging quality (HR 3.84, 95%CI 1.12-13.19; p = 0.03), and inter-clip distance (HR 1.60, 95%CI 1.27-2.02; p < 0.01) were associated with the occurrence of the primary endpoint. CONCLUSIONS: Recurrence of severe MR after a MitraClip procedure for primary MR results from a complex interplay between anatomical (tissue excess) and procedural criteria (quality of ultrasound guidance and MitraClips spacing).

Participating in Sports After Mitral Valve Repair for Primary Mitral Regurgitation: A Retrospective Cohort Study.

OBJECTIVE: Participating in either competitive or leisure sports is restrictive after surgical mitral valve repair (MVR). In this study, we examine the impact of sports on outcomes after MVR. DESIGN: Retrospective cohort study. SETTING: Patients aged 18 to 65 years who underwent a first-time MVR for primary mitral regurgitation (MR) in a tertiary care center. PATIENTS: One hundred twenty-one consecutive patients were included in the study. The exclusion criteria were as follows: other concomitant procedures, early perioperative death or repeat intervention, noncardiac death or endocarditis during follow-up, and general contraindications for normal physical activity. ASSESSMENT OF RISK FACTORS: Participation in sports was quantified by the number of hours per week during the past 6 months, classified according to the Mitchell classification and assessed with the International Physical Activity Questionnaire (IPAQ) short form. MAIN OUTCOME MEASURES: The primary composite endpoint was MVR failure defined as MR grade ≥2 or mean transmitral gradient ≥8 mm Hg, signs and symptoms of heart failure, or late-onset postoperative AF (>3 months). RESULTS: The mean age was 50 ± 11 years, and there were 85 (71%) men. The median follow-up was 34 months [interquartile range (IQR): 20-50]. Fifty-six (46%) patients participated in sports regularly (median of 3 h/wk; IQR: 2-5). Twenty (17%) patients reached the primary composite endpoint with no correlation with participation in sports (P = 0.537), IPAQ categories (P = 0.849), in any of the Mitchell classification subgroups and a high level of participation in sports ≥6 hours (P = 0.679). CONCLUSIONS: Sports seem to be unrelated to the worst outcome after MVR.

A Prospective Study Identifying Predictive Factors of Cardiac Decompensation After Transjugular Intrahepatic Portosystemic Shunt: The Toulouse Algorithm.

BACKGROUND AND AIMS: Transjugular intrahepatic portosystemic shunt (TIPS) is now a standard for the treatment of portal hypertension-related complications. After the TIPS procedure, incidence and risk factors of cardiac decompensation are poorly known. The main objectives were to measure the incidence of the onset of cardiac decompensation after TIPS and identify the predictive factors. APPROACH AND RESULTS: All patients with cirrhosis treated with TIPS between May 2011 and June 2016 were considered for inclusion. They received a cardiac assessment by standard biological parameters, transthoracic echocardiography, and right heart catheterization. Patients were followed for 1 year after TIPS insertion. The main endpoint was the incidence of cardiac decompensation requiring hospitalization. One hundred seventy-four patients were treated by TIPS during the period. One hundred patients who underwent a complete cardiac evaluation were included. A cardiac decompensation occurred in 20% of the patients. The parameters associated with the occurrence of severe cardiac decompensation were a prolonged QT interval corrected (462 vs. 443 ms; P = 0.05), an elevated pre-TIPS brain natriuretic peptide (BNP) or N-terminal pro-brain natriuretic peptide (NT-proBNP) level, an elevated E/A ratio (1.5 vs. 1.0; P = 0.001) and E/e' ratio (11 vs. 7; P < 0.001), and a left atrial dilatation (40 vs. 29 mL/m2 ; P = 0.011). The presence of aortic stenosis was also associated with cardiac decompensation. A level of BNP <40 pg/mL and NT-proBNP <125 pg/mL allowed identifying patients without risk of cardiac decompensation. Additionally, absence of diastolic dysfunction criteria at echocardiography ruled out the risk of further cardiac decompensation. CONCLUSIONS: Hospitalization for cardiac decompensation is observed in 20% of patients in the year after TIPS insertion. Combining BNP or NT-proBNP levels and echocardiographic parameters should help improve patient selection.

Pattern of myocardial 99mTc-HMDP uptake and impact on myocardial function in patients with transthyretin cardiac amyloidosis.

AIMS: The purpose of the study was to describe the pattern of 99mTc-labeled phosphate agents myocardial uptake by scintigraphy and explore its impact on left ventricular (LV) functions in transthyretin cardiac amyloidosis (TTR-CA). METHODS: Fifty patients with TTR-CA underwent 99mTc- hydroxymethylene-diphosphonate (99mTc-HMDP) scintigraphy and echocardiography with measure of LV thickness, longitudinal strain (LS), systolic and diastolic functions. Cardiac retention by scintigraphy was assessed by visual scoring and the heart/whole body (H/WB) ratio was calculated by dividing counts in the heart by counts in late whole-body images. RESULTS: The mean population age was 79 ± 10 years. Mean H/WB ratio was 12 ± 7. Myocardial 99mTc-HMDP uptake on segments 5, 6, 7, 8, 11, 12, 13, 14, 16, and 17 was correlated with H/WB ratio. Mean LVEF and global LS were 51 ± 10% and - 10 ± 3%, respectively. H/WB ratio was correlated with global LS (R = 0.408, P = .003), Ea (R = - 0.566, P < .001) and mean left ventricular wall thickness (R = 0.476, P < .001) but not with LVEF (R = - 0.109, P = .453). Segmental myocardial uptake was slightly correlated with segmental LS (R = 0.152, P < .001). H/WB ratio was not correlated with NT-proBNP levels (R = 0.219, P = .148) neither E/Ea ratio (R = 0.204, P = .184). CONCLUSION: These findings show the relationship between bone tracer myocardial uptake and LV functions in patients with TTR cardiac amyloidosis.

Cardiac impact of arteriovenous fistulas: what tools to assess?

The relationship between arteriovenous access flow (Qa) and cardiovascular changes is complex. Several studies have shown cardiac remodeling and symptoms of heart failure for high-flow arteriovenous fistulas (AVF). To evaluate the early cardiovascular impact of AVF. Forty-seven patients with an AVF, hospitalized for the evaluation of high-flow AVF or a pre-kidney transplant assessment were included. We collected clinical and biological data. We also collected data of the assessment by transthoracic echocardiography, functional evaluation by 6-min-walk test and peak oxygen consumption, and measurement of coronary flow reserve by dynamic myocardial perfusion imaging. The measurement of Qa was performed by color Doppler ultrasound and then indexed to the body surface area (Qai) and to the cardiac output (CO) (Qa/CO). Patients were poorly symptomatic (18 and 1 patients NYHA stage 2 and 3, respectively). There was no correlation between Qa, Qai, or Qa/CO and functional status, assessed by peak oxygen consumption (P = 0.891; P = 0.803; P = 0.939, respectively). Symptomatic patients did not have higher Qa, Qai or Qa/CO than asymptomatic (2260 vs 2197 mL/min, P = 0.402; 1257 vs 1256 mL/min/m2, P = 0.835; and 34% vs 37%, P = 0.701, respectively). There was no correlation between Qa, Qai or Qa/CO and left ventricular end-diastolic volume or left ventricular ejection fraction. There was no correlation between coronary flow reserve and these 3 parameters of vascular access flow. However, the global longitudinal strain (GLS) was correlated with Qa and Qa/CO (R = 0.331, P = 0.023 and R = 0.380, P = 0.008, respectively). Increase of Qa or Qa/CO was associated with an alteration of the GLS. A cut-off value of 2250 mL/min for Qa allowed 83% sensitivity and 63% specificity for detecting an alteration of the GLS > - 18%. A cut-off value of 33% for Qa/CO allowed 92% sensitivity and 65% specificity. Impact of AVF on cardiac parameters is weak. However, GLS is the first parameter to be impacted by the flow of the fistula. Systematic transthoracic echocardiography evaluation with measurement of GLS should be proposed for all patients with Qa > 2250 mL/min or Qa/CO > 33%, to detect those at higher risk of cardiac impact of the AVF.

What is the most useful imaging parameter to explore the prognostic value of the right ventricular function at the time of multimodality cardiovascular imaging?

BACKGROUND: Right ventricular (RV) function is a powerful independent predictor of adverse heart failure outcomes. The aim of this study was to compare the predictive value of main RV systolic imaging parameters for outcome. METHODS: Seventy-nine patients underwent comprehensive cardiovascular imaging modalities including transthoracic echocardiography, cardiac magnetic resonance (CMR) imaging, and tomographic equilibrium radionuclide ventriculography (ERV) for the assessment of RV function. The composite primary endpoint (CPE) was defined by the occurrence of death, heart transplantation, implantation of a left ventricular assist device, or new-onset acute heart failure. RESULTS: During a mean follow-up of 13 ± 9 months, 15 (19%) patients reached the CPE. The areas under the receiver operator characteristic curves for the prediction of the CPE were 0.922 (P < .001), 0.913 (P < .001), 0.906 (P < .001), 0.849 (P = .002), 0.837 (P = .003), 0.799 (P = .009), 0.792 (P = .011), 0.753 (P = .026), 0.720 (P = .053), and 0.608 (P = .346) for integral systolic S' wave tricuspid annular velocity, RV free wall longitudinal strain (RVFWLS), RV fractional area change, tricuspid annular plane systolic excursion, RV ejection fraction (RVEF) by CMR using the 4-chamber slices, peak systolic S' wave tricuspid annular velocity, RVEF by CMR using short-axis slices, RVEF by ERV, RV myocardial performance index, and RV myocardial acceleration during isovolumic contraction, respectively. CONCLUSION: Echocardiographic parameters, and particularly integral systolic S' wave tricuspid annular velocity and RVFWLS, have the best prognostic performance.

Impact of right ventricular systolic function after heart transplantation on exercise capacity.

BACKGROUND: Right ventricular (RV) systolic parameters are difficult to assess in heart transplant recipients (HTRs) compared to healthy people because of discordant data, and their impact on exercise capacity remains undefined. We sought to retrospectively assess the impact of RV systolic function on exercise capacity after heart transplantation. METHODS: We analyzed data from 61 HTRs who underwent transthoracic echocardiography (TTE), cardiac magnetic resonance imaging (CMR), and exercise capacity assessment by 6-minute walking test (6MWT) and cardiopulmonary exercise testing (CPET) at 1- and 2-year follow-ups. RESULTS: Transthoracic echocardiography RV longitudinal systolic function including tricuspid annular plan systolic excursion (TAPSE), peak systolic S' wave tricuspid annular velocity (PSVtdi) and RV free wall longitudinal strain was decreased at 1 year (respectively, 15 ± 3 mm, 10 ± 3 cm/s, and -19 ± 5%) and at 2 years (respectively, 15 ± 3 mm, 10 ± 2 cm/s, and -20 ± 5%) with no significant difference between both evaluations; meanwhile, RV ejection fraction (RVEF) measured by CMR was preserved. Mean percentage of predicted peak oxygen consumption was altered, but improved between the first and second year (55 ± 18 vs 60 ± 18%, P = .038). PSVtdi was weakly correlated with 6MWT distance (r = .426, P = .017) and RVEF with the predicted distance at 6MWT (r = .410, P = .027) at the 1-year follow-up. CONCLUSIONS: Despite decreasing values, RV longitudinal systolic function has a weak impact on exercise capacity of HTRs. PSVtdi and RVEF are the most pertinent parameters to assess the impact of RV systolic function on exercise capacity after heart transplantation. These results should lead to redefine normal RV systolic function thresholds for HTRs.

Multifunctional Mitochondrial Epac1 Controls Myocardial Cell Death.

RATIONALE: Although the second messenger cyclic AMP (cAMP) is physiologically beneficial in the heart, it largely contributes to cardiac disease progression when dysregulated. Current evidence suggests that cAMP is produced within mitochondria. However, mitochondrial cAMP signaling and its involvement in cardiac pathophysiology are far from being understood. OBJECTIVE: To investigate the role of MitEpac1 (mitochondrial exchange protein directly activated by cAMP 1) in ischemia/reperfusion injury. METHODS AND RESULTS: We show that Epac1 (exchange protein directly activated by cAMP 1) genetic ablation (Epac1-/-) protects against experimental myocardial ischemia/reperfusion injury with reduced infarct size and cardiomyocyte apoptosis. As observed in vivo, Epac1 inhibition prevents hypoxia/reoxygenation-induced adult cardiomyocyte apoptosis. Interestingly, a deleted form of Epac1 in its mitochondrial-targeting sequence protects against hypoxia/reoxygenation-induced cell death. Mechanistically, Epac1 favors Ca2+ exchange between the endoplasmic reticulum and the mitochondrion, by increasing interaction with a macromolecular complex composed of the VDAC1 (voltage-dependent anion channel 1), the GRP75 (chaperone glucose-regulated protein 75), and the IP3R1 (inositol-1,4,5-triphosphate receptor 1), leading to mitochondrial Ca2+ overload and opening of the mitochondrial permeability transition pore. In addition, our findings demonstrate that MitEpac1 inhibits isocitrate dehydrogenase 2 via the mitochondrial recruitment of CaMKII (Ca2+/calmodulin-dependent protein kinase II), which decreases nicotinamide adenine dinucleotide phosphate hydrogen synthesis, thereby, reducing the antioxidant capabilities of the cardiomyocyte. CONCLUSIONS: Our results reveal the existence, within mitochondria, of different cAMP-Epac1 microdomains that control myocardial cell death. In addition, our findings suggest Epac1 as a promising target for the treatment of ischemia-induced myocardial damage.

Impact of video on the understanding and satisfaction of patients receiving informed consent before elective inpatient coronary angiography: A randomized trial.

BACKGROUND: Appropriate information about the benefits and risks of invasive procedures is crucial, but limited data is available in this field. The aim of this study was to evaluate the incremental value of a short video about coronary angiography compared with standard information, in terms of patient understanding, satisfaction and anxiety. METHODS: This prospective multicenter study included patients admitted for scheduled coronary angiography, who were randomized to receive either standard information or video information by watching a three-dimensional educational video. After information was delivered, patients were asked to complete a dedicated 16-point information questionnaire, as well as satisfaction and anxiety scales. RESULTS: From 21 September to 4 October 2015, 821 consecutive patients were randomized to receive either standard information (n=415) or standard information with an added educational video (n=406). The information score was higher in the video information group than in the standard group (11.8±2.8 vs 9.5±3.1; P<.001). This result was consistent across age and education level subgroups. Self-reported satisfaction was also higher in the video information group (8.4±1.9 vs. 7.7±2.3; P<.001), while anxiety level did not differ between groups. The variables associated with a higher information score were the use of the educational video, younger age, higher level of education, previous follow-up by a cardiologist, prior information about coronary angiography and previous coronary angiography. CONCLUSIONS: In comparison with standard information, viewing a dedicated educational video improved patients' understanding and satisfaction before scheduled coronary angiography. These results are in favor of widespread use of this incremental information tool.

Outcomes after use of covered stents to treat coronary artery perforations. Comparison of old and new-generation covered stents.

OBJECTIVES: To compare outcomes in patients receiving polytetrafluoroethylene (PTFE) and polyurethane (PL) covered stents (CS) after coronary artery perforation (CAP). BACKGROUND: The prognosis of CAP has improved with the advent of CSs. Information is scarce about the outcomes of new-generation CSs. METHODS: Sixty-one patients were treated with CSs in a 5-years period (age = 77 ± 8.75% males). Procedural and clinical data were retrospectively collected. The primary endpoint was procedural success. Secondary endpoints included death and major adverse cardiac events (MACE) defined as a composite of death, myocardial infarction, target vessel, and lesion revascularization and need for surgical repair). RESULTS: Twenty-two (36%) received PL-CSs and 39 (65%) PTFE-CSs. There were no differences in procedural success (86% vs 69%, P = 0.216). Time to deliver was shorter with PL-CS despite larger length of stents (8[11] vs 15[16] min, P = 0.001; 20[5] vs 16[3] mm, P < 0.001). This group had lower rate of pericardial effusion and cardiac arrest (41% vs 72%, P = 0.028; 5% vs 26%, P = 0.045). At 1-year follow-up, MACE rates were similar (58% vs 56%, P = 1.000) with atrend toward TVR in the PL-CS arm (21% vs 5%, P = 0.083). No differences were found in mortality (26% vs 41%, P = 0.385). Each group had 1 stent thrombosis and in-stent restenosis trended higher in the PL-CS group (12% vs 3%, P = 0.223). CONCLUSIONS: Time to deliver was shorter with the PL-CS and resulted in lower rate of pericardial effusion and cardiac arrest. However, there were no significant differences in procedural success and 1-year follow-up MACE in patients treated with PL-CS or PTFE-CS.

Prognostic impact of myocardial perfusion single photon emission computed tomography in patients with major extracardiac findings by computed tomography for attenuation correction.

BACKGROUND: Attenuation correction computed tomography (CT) contributes to an improvement in the diagnostic accuracy of myocardial perfusion imaging (MPI) by single photon emission tomography (SPECT). The aim of this study was to explore the prognosis of patients with major findings by CT according to the results of MPI. METHODS AND RESULTS: 1506 patients who underwent MPI by SPECT were retrospectively included. Attenuation correction CT images were systematically analyzed for major and minor abnormalities. 830 (55.1%) and 212 (14.1%) patients had minor and major extracardiac findings, respectively. Among patients with major extracardiac findings, the abnormality was previously unknown in 113 (53.3%) patients. 90 (41.9%) had abnormal MPI, 73 (34.4%) had a myocardial infarction scar, 55 (25.9%) had myocardial ischemia, and 38 (17.7%) patients had both myocardial infarction scar and myocardial ischemia. Among the 201 patients available for survival analysis, there were 67 (31.2%) deaths over a follow-up period of 3.2±1.3 years. There was no significant impact on survival arising from MPI, whatever the result. The results were the same among the 103 patients with previously unknown major extracardiac findings. CONCLUSION: Extracardiac findings by CT during MPI are frequent. Patients with major extracardiac findings have a poor mid-term outcome, whatever the results of the myocardial perfusion imaging. Extracardiac findings should be systematically checked when attenuation correction CT is performed.