Cardiac Magnetic Resonance Identifies Responders to Cardiac Resynchronization Therapy with an Assessment of Septal Scar and Left Ventricular Dyssynchrony.

Background: The response to cardiac resynchronization therapy (CRT) depends on septal viability and correction of abnormal septal motion. This study investigates if cardiac magnetic resonance (CMR) as a single modality can identify CRT responders with combined imaging of pathological septal motion (septal flash) and septal scar. Methods: In a prospective, multicenter, observational study of 136 CRT recipients, septal scar was assessed using late gadolinium enhancement (LGE) (n = 127) and septal flash visually from cine CMR sequences. The primary endpoint was CRT response, defined as ≥15% reduction in LV end-systolic volume with echocardiography after 6 months. The secondary endpoint was heart transplantation or death of any cause assessed after 39 ± 13 months. Results: Septal scar and septal flash were independent predictors of CRT response in multivariable analysis (both p < 0.001), while QRS duration and morphology were not. The combined approach of septal scar and septal flash predicted CRT response with an area under the curve of 0.86 (95% confidence interval (CI): 0.78-0.94) and was a strong predictor of long-term survival without heart transplantation (hazard ratio 0.27, 95% CI: 0.10-0.79). The accuracy of the approach was similar in the subgroup with intermediate (130-150 ms) QRS duration. The combined approach was superior to septal scar and septal flash alone (p < 0.01). Conclusions: The combined assessment of septal scar and septal flash using CMR as a single-image modality identifies CRT responders with high accuracy and predicts long-term survival.

Approach to optimal assessment of right ventricular remodelling in heart transplant recipients: insights from myocardial work index, T1 mapping, and endomyocardial biopsy.

AIMS: Right ventricular (RV) dysfunction is an important cause of graft failure after heart transplantation (HTx). We sought to investigate relative merits of echocardiographic tools and cardiac magnetic resonance (CMR) with T1 mapping for the assessment of functional adaptation and remodelling of the RV in HTx recipients. METHODS AND RESULTS: Sixty-one complete data set of echocardiography, CMR, right heart catheterization, and biopsy were obtained. Myocardial work index (MWI) was quantified by integrating longitudinal strain (LS) with invasively measured pulmonary artery pressure. CMR derived RV volumes, T1 time, and extracellular volume (ECV) were quantified. Endomyocardial biopsy findings were used as the reference standard for myocardial microstructural changes. In HTx recipients who never had a previous allograft rejection, longitudinal function parameters were lower than healthy organ donors, while ejection fraction (EF) (52.0 ± 8.7%) and MWI (403.2 ± 77.2 mmHg%) were preserved. Rejection was characterized by significantly reduced LS, MWI, longer T1 time, and increased ECV that improved after recovery, whereas RV volumes and EF did not change MWI was the strongest determinant of rejection related myocardial damage (area under curve: 0.812, P < 0.0001, 95% CI: 0.69-0.94) with good specificity (77%), albeit modest sensitivity. In contrast, T1 time and ECV were sensitive (84%, both) but not specific to detect subclinical RV damage. CONCLUSION: Subclinical adaptive RV remodelling is characterized by preserved RV EF despite longitudinal function abnormalities, except for MWI. While ultrastructural damage is reflected by MWI, ECV, and T1 time, only MWI has the capability to discriminate functional adaptation from transition to subclinical structural damage.

Multi-modality imaging assessment of native valvular regurgitation: an EACVI and ESC council of valvular heart disease position paper.

Valvular regurgitation represents an important cause of cardiovascular morbidity and mortality. Imaging is pivotal in the evaluation of native valve regurgitation and echocardiography is the primary imaging modality for this purpose. The imaging assessment of valvular regurgitation should integrate quantification of the regurgitation, assessment of the valve anatomy and function, and the consequences of valvular disease on cardiac chambers. In clinical practice, the management of patients with valvular regurgitation largely relies on the results of imaging. It is crucial to provide standards that aim at establishing a baseline list of measurements to be performed when assessing native valve regurgitation. The present document aims to present clinical guidance for the multi-modality imaging assessment of native valvular regurgitation.

Percutaneous mitral valve repair in severe secondary mitral regurgitation: Analysis of index hospitalization and economic evaluation based on the MITRA-FR trial.

BACKGROUND: Percutaneous mitral valve repair (pMVR) is reimbursed in France for severe secondary mitral regurgitation (SMR), but French data regarding the hospitalization index stay are lacking. AIMS: Our objectives were to describe the index hospitalization stay and to evaluate the cost of hospital stay for pMVR used in SMR. METHODS: A secondary evaluation based on patients who were randomized to the intervention group of the MITRA-FR study was undertaken. The economic evaluation was conducted according to the French hospital perspective. Medical resource use was estimated using specific data collected from patients enrolled in the MITRA-FR study and non-specific data from national statistics. RESULTS: The population was represented by 144 patients who underwent pMVR at 33 French centres. There was a mean±standard deviation of 7.9±1.5 hospital staff during procedures. The mean procedure duration was 154±68 minutes and increased with the number of implanted clips. Median total length of stay was 8 days. The occurrence of a serious adverse event was not associated with an increased risk of admission to the critical care unit, but was associated with an increased length of stay. The mean total cost was 28,025±3424€, which includes 21,547€ for the cost of medical devices used during pMVR and 6478±3424€ for other costs. CONCLUSION: The cost of pMVR is substantial for patients with SMR, which advocates for further efforts to identify the patients with SMR who are likely to derive a clear clinical benefit from the procedure.

Importance of Systematic Right Ventricular Assessment in Cardiac Resynchronization Therapy Candidates: A Machine Learning Approach.

BACKGROUND: Despite all having systolic heart failure and broad QRS intervals, patients screened for cardiac resynchronization therapy (CRT) are highly heterogeneous, and it remains extremely challenging to predict the impact of CRT devices on left ventricular function and outcomes. The aim of this study was to evaluate the relative impact of clinical, electrocardiographic, and echocardiographic data on the left ventricular remodeling and prognosis of CRT candidates by the application of machine learning approaches. METHODS: One hundred ninety-three patients with systolic heart failure receiving CRT according to current recommendations were prospectively included in this multicenter study. A combination of the Boruta algorithm and random forest methods was used to identify features predicting both CRT volumetric response and prognosis. Model performance was tested using the area under the receiver operating characteristic curve. The k-medoid method was also applied to identify clusters of phenotypically similar patients. RESULTS: From 28 clinical, electrocardiographic, and echocardiographic variables, 16 features were predictive of CRT response, and 11 features were predictive of prognosis. Among the predictors of CRT response, eight variables (50%) pertained to right ventricular size or function. Tricuspid annular plane systolic excursion was the main feature associated with prognosis. The selected features were associated with particularly good prediction of both CRT response (area under the curve, 0.81; 95% CI, 0.74-0.87) and outcomes (area under the curve, 0.84; 95% CI, 0.75-0.93). An unsupervised machine learning approach allowed the identification of two phenogroups of patients who differed significantly in clinical variables and parameters of biventricular size and right ventricular function. The two phenogroups had significantly different prognosis (hazard ratio, 4.70; 95% CI, 2.1-10.0; P < .0001; log-rank P < .0001). CONCLUSIONS: Machine learning can reliably identify clinical and echocardiographic features associated with CRT response and prognosis. The evaluation of both right ventricular size and functional parameters has pivotal importance for the risk stratification of CRT candidates and should be systematically performed in patients undergoing CRT.

New expectations for diastolic function assessment in transthoracic echocardiography based on a semi-automated computing of strain-volume loops.

AIMS: Early diagnosis of heart failure with preserved ejection fraction (HFpEF) by determination of diastolic dysfunction is challenging. Strain-volume loop (SVL) is a new tool to analyse left ventricular function. We propose a new semi-automated method to calculate SVL area and explore the added value of this index for diastolic function assessment. METHOD AND RESULTS: Fifty patients (25 amyloidosis, 25 HFpEF) were included in the study and compared with 25 healthy control subjects. Left ventricular ejection fraction was preserved and similar between groups. Classical indices of diastolic function were pathological in HFpEF and amyloidosis groups with greater left atrial volume index, greater mitral average E/e' ratio, faster tricuspid regurgitation (P < 0.0001 compared with controls). SVL analysis demonstrated a significant difference of the global area between groups, with the smaller area in amyloidosis group, the greater in controls and a mid-range value in HFpEF group (37 vs. 120 vs. 72 mL.%, respectively, P < 0.0001). Applying a linear discriminant analysis (LDA) classifier, results show a mean area under the curve of 0.91 for the comparison between HFpEF and amyloidosis groups. CONCLUSION: SVLs area is efficient to identify patients with a diastolic dysfunction. This new semi-automated tool is very promising for future development of automated diagnosis with machine-learning algorithms.

Model-based estimation of left ventricular pressure and myocardial work in aortic stenosis.

This paper proposes a model-based estimation of left ventricular (LV) pressure for the evaluation of constructive and wasted myocardial work of patients with aortic stenosis (AS). A model of the cardiovascular system is proposed, including descriptions of i) cardiac electrical activity, ii) elastance-based cardiac cavities, iii) systemic and pulmonary circulations and iv) heart valves. After a sensitivity analysis of model parameters, an identification strategy was implemented using a Monte-Carlo cross-validation approach. Parameter identification procedure consists in two steps for the estimation of LV pressures: step 1) from invasive, intraventricular measurements and step 2) from non-invasive data. The proposed approach was validated on data obtained from 12 patients with AS. The total relative errors between estimated and measured pressures were on average 11.9% and 12.27% and mean R2 were equal to 0.96 and 0.91, respectively for steps 1 and 2 of parameter identification strategy. Using LV pressures obtained from non-invasive measurements (step 2) and patient-specific simulations, Global Constructive (GCW), Wasted (GWW) myocardial Work and Global Work Efficiency (GWE) parameters were calculated. Correlations between measures and model-based estimations were 0.88, 0.80, 0.91 respectively for GCW, GWW and GWE. The main contributions concern the proposal of the parameter identification procedure, applied on an integrated cardiovascular model, able to reproduce LV pressure specifically to each AS patient, by non-invasive procedures, as well as a new method for the non-invasive estimation of constructive, wasted myocardial work and work efficiency in AS.

Assessment of Subclinical Left Ventricular Dysfunction in Aortic Stenosis.

Left ventricular (LV) systolic dysfunction is an adverse consequence of the pressure overload of severe aortic stenosis (AS). The enlargement of the interstitial space with reactive fibrosis and subsequently with replacement fibrosis and cell death has been suggested to be the main driver of the transition to symptoms, heart failure, and adverse cardiovascular events even after aortic valve replacement (AVR). Early and accurate recognition of myocardial dysfunction offers the potential to optimize the timing of intervention in severe AS. In the asymptomatic patient, an LV ejection fraction (EF) cutpoint of <50% has been used for this purpose. However, in most asymptomatic patients, an LVEF <50% is uncommon, and patients with an LVEF of 50% to 59% fare almost as badly. Moreover, the presence of a small LV cavity, the reliability and automation of the global longitudinal strain (GLS) signal, and the independent prognostic role of GLS are reasons why GLS could be expected to be a better marker of subclinical LV dysfunction in these patients. This review seeks to define whether the existing EF cutoff in AS should be modified or whether GLS should replace it as the marker of subclinical LV dysfunction.

close: Closure of patent foramen ovale, oral anticoagulants or antiplatelet therapy to prevent stroke recurrence: Study design.

RATIONALE: Currently available data do not provide definitive evidence on the comparative benefits of closure of patent foramen ovale, oral anticoagulants and antiplatelet therapy in patients with patent foramen ovale-associated cryptogenic stroke AIM: To assess whether transcatheter patent foramen ovale closure plus antiplatelet therapy is superior to antiplatelet therapy alone and whether oral anticoagulant therapy is superior to antiplatelet therapy, for secondary stroke prevention in patients aged 16 to 60 years with a large patent foramen ovale or a patent foramen ovale associated with an atrial septal aneurysm, and an otherwise unexplained ischaemic stroke or retinal ischaemia. SAMPLE SIZE: Six hundred and sixty-four patients were included in the study. METHODS AND DESIGN: CLOSE is an academic-driven, multicentre, randomized, open-label, three-group, superiority trial with blinded adjudication of outcome events. The trial has been registered with Clinical Trials Register (Clinicaltrials.gov, NCT00562289). Patient recruitment started in December 2007. Patient follow-up will continue until December 2016. Expected mean follow-up = 5.6 years. STUDY OUTCOMES: The primary efficacy outcome is the occurrence of fatal or nonfatal stroke. Safety outcomes include fatal, life-threatening or major procedure- or device-related complications and fatal, life-threatening or major haemorrhagic complications. DISCUSSION: CLOSE is the first specifically designed trial to assess the superiority of patent foramen ovale closure over antiplatelet therapy alone and the superiority of oral anticoagulants over antiplatelet therapy to prevent stroke recurrence in patients with patent foramen ovale-associated cryptogenic stroke.

Multimodality Imaging Strategies for the Assessment of Aortic Stenosis: Viewpoint of the Heart Valve Clinic International Database (HAVEC) Group.

Aortic stenosis is the most frequent valvular heart disease. In aortic stenosis, therapeutic decision essentially depends on symptomatic status, stenosis severity, and status of left ventricular systolic function. Surgical aortic valve replacement or transcatheter aortic valve implantation is the sole effective therapy in symptomatic patients with severe aortic stenosis, whereas the management of asymptomatic patients remains controversial and is mainly based on individual risk stratification. Imaging is fundamental for the initial diagnostic work-up, follow-up, and selection of the optimal timing and type of intervention. The present review provides specific recommendations for utilization of multimodality imaging to optimize risk stratification and therapeutic decision-making processes in aortic stenosis.

Recognition and significance of pathological T-wave inversions in athletes.

BACKGROUND: Pathological T-wave inversion (PTWI) is rarely observed on the ECG of healthy athletes, whereas it is common in patients with certain cardiac diseases. All ECG interpretation guidelines for use within athletes state that PTWI (except in leads aVR, III and V1 and in V1-V4 when preceded by domed ST segment in asymptomatic Afro-Caribbean athletes only) cannot be considered a physiological adaptation. The aims of the present study were to prospectively determine the prevalence of cardiac pathology in athletes presenting with PTWI, and to examine the efficacy of cardiac magnetic resonance in the work-up battery of further examinations. METHODS AND RESULTS: Athletes presenting with PTWI (n=155) were investigated with clinical examination, ECG, echocardiography, exercise testing, 24h Holter ECG, and cardiac magnetic resonance. Cardiac disease was established in 44.5% of athletes, with hypertrophic cardiomyopathy (81%) the most common pathology. Echocardiography was abnormal in 53.6% of positive cases, and cardiac magnetic resonance identified a further 24 athletes with disease. Five athletes (7.2%) considered normal on initial presentation subsequently expressed pathology during follow-up. Familial history of sudden cardiac death and ST-segment depression associated with PTWI were predictive of cardiac disease. CONCLUSIONS: PTWI should be considered pathological in all cases until proven otherwise, because it was associated with cardiac pathology in 45% of athletes. Despite echocardiography identifying pathology in half of these cases, cardiac magnetic resonance must be considered routine in athletes presenting with PTWI with normal echocardiography. Although exclusion from competitive sport is not warranted in the presence of normal secondary examinations, annual follow-up is essential to ascertain possible disease expression.

LV mechanics in mitral and aortic valve diseases: value of functional assessment beyond ejection fraction.

The assessment of myocardial function in the context of valvular heart disease remains highly challenging. The myocardium deforms simultaneously in 3 dimensions, and global left ventricular (LV) function parameters such as volume and ejection fraction may remain compensated despite the changes in myocardial deformation properties. Current guidelines recommend valve replacement/repair in the presence of symptoms or reduced LV ejection fraction, but the resolution of symptoms or recovery of LV function post-surgery may not be reliably predicted. A wealth of evidence currently suggests that LV dysfunction is frequently subclinical despite normal ejection fraction. It may precede the onset of symptoms and portend a poor outcome due to progressive myocardial remodeling and dysfunction during the post-operative period. The advent of novel tissue-tracking echocardiography techniques has unleashed new opportunities for the clinical identification of early abnormalities in LV function. This review gathers and summarizes current evidence regarding the use of these techniques to assess myocardial deformation in patients with valvular heart disease.

A plea for the wider use of CRT-P in candidates for cardiac resynchronisation therapy.

Spectacular developments have taken place, in the last 10 years, in the device-based management of heart failure (HF). Patients presenting with chronic HF may benefit from a device implanted with a view to: (1) resynchronise the pump function of a discoordinated failing heart or (2) prevent sudden arrhythmic death by automatic cardioversion or defibrillation. This "point-of-view" article reviews the large amount of information gathered in the past 10 years on the use of cardiac resynchronisation therapy (CRT), with or without cardioverter defibrillator (ICD), and puts in perspective the advisability of using one, the other or both treatments in distinct patient subsets. There is currently no strong scientific evidence supporting the systematic implantation of CRT-ICD (CRT-D) instead of CRT pacemakers (CRT-P). Plain common sense should limit the prescription of these costly and complicated devices to patients in need of secondary prevention of ventricular arrhythmias or, for primary prevention, in younger patients without major concomitant illnesses. The preferential choice of CRT-P for the remainder of ambulatory patients in New York Heart Association (NYHA) functional class III or IV is currently acceptable. Because of insufficient data regarding the performance of CRT-P in patients presenting in NYHA functional class I or II, CRT-D is currently the device of choice for this sub-population.

Importance of ventricular longitudinal function in chronic heart failure.

AIMS: Despite its immediate relevance, cardiopulmonary exercise testing (CPET) is infrequently performed in the presence of chronic heart failure (CHF). Previous studies of patients suffering from CHF have found a closer correlation between exercise capacity and measurements of diastolic than systolic ventricularfunction. We examined the correlation between echocardiographic measurements and (i) results of CPET and (ii) cardiovascular prognosis. METHODS AND RESULTS: We performed resting two-dimensional echocardiograms and CPET in 140 patients with CHF (mean age = 61 ± 13 years, 111 men). The underlying heart disease was ischaemic in 48 patients (34%). They were followed for a mean of 38 months (range 28-52). The mean left ventricular (LV) ejection fraction (EF) was 30 ± 9% and peak VO2 17.2 ± 6.5 mL/kg/min. LVEF correlated weakly with peak VO2 (r = 0.21), while systolic and early diastolic LV longitudinal function correlated best [early diastolic peak velocity at the mitral annulus (E'): r = 0.38; global longitudinal strain (GLS): r = -0.4; P <0.001 for both]. By multiple variable regression analysis, the best prediction of peak VO2 was derived from a model based on age, mitral annulus end-diastolic peak velocity (A'), GLS, right ventricular (RV) systolic strain, and left atrial systolic strain (r² = 0.57; P <0.0001). The two best independent predictors of adverse cardiovascular events at 28 months were GLS (odds ratio 1.31, P <0.001; prognostic cut-off = -8%) and RV systolicstrain (odds ratio 1.05, P =0.01; prognostic cut-off = -22%). CONCLUSION: Resting RV and LV longitudinal functions were reliable predictors of adverse cardiovascular events and correlated moderately with, but not took to the place of, CPET measurements.

Speckle tracking imaging improves in vivo assessment of EPO-induced myocardial salvage early after ischemia-reperfusion in rats.

A noninvasive assessment of infarct size and transmural extension of myocardial infarction (TEMI) is fundamental in experimental models of ischemia-reperfusion. Conventional echocardiography parameters are limited in this purpose. This study was designed to examine whether speckle tracking imaging can be used in a rat model of ischemia-reperfusion to accurately detect the reduction of infarct size and TEMI induced by erythropoietin (EPO) as early as 24 h after reperfusion. Rats were randomly assigned to one of three groups: myocardial infarction (MI)-control group, 45 min ischemia followed by 24 h of reperfusion; MI-EPO group, similar surgery with a single bolus of EPO administered at the onset of reperfusion; and sham-operated group. Short-axis two-dimensional echocardiography was performed after reperfusion. Global radial (GS(r)) and circumferential (GS(cir)) strains were compared with infarct size and TEMI assessed after triphenyltetrazolium chloride staining. As a result, ejection fraction, shortening fraction, GS(r), and GS(cir) significantly correlated to infarct size, whereas only GS(r) and GS(cir) significantly correlated to TEMI. EPO significantly decreased infarct size (30.8 + or - 3.5 vs. 56.2 + or - 5.7% in MI-control, P < 0.001) and TEMI (0.37 + or - 0.05 vs. 0.77 + or - 0.05 in MI-control, P < 0.001). None of the conventional echocardiography parameters was significantly different between the MI-EPO and MI-control groups, whereas GS(r) was significantly higher in the MI-EPO group (29.1 + or - 4.7 vs. 16.4 + or - 3.3% in MI-control; P < 0.05). Furthermore, GS(cir) and GS(r) appeared to be the best parameters to identify a TEMI >0.75 24 h after reperfusion. In conclusion, these findings demonstrate the usefulness of speckle tracking imaging in the early evaluation of a cardioprotective strategy in a rat model of ischemia-reperfusion.