Myocardial deformation after radiotherapy: a layer-specific and territorial longitudinal strain analysis in a cohort of left-sided breast cancer patients (BACCARAT study).

BACKGROUND: Radiotherapy for breast cancer (BC) and its resulting cardiac exposure are associated with subclinical left ventricular dysfunction characterized by early decrease of global longitudinal strain (LS) measurement based on 2D speckle-tracking echocardiography. Recent software allows multi-layer and segmental analysis of strain, which may be of interest to quantify and locate the impact of cardiac exposure on myocardial function and potentially increase the early detection of radiation-induced cardiotoxicity. The aim of the study was to evaluate whether decrease in LS 6 months after radiotherapy is layer-specific and if it varies according to the left ventricular regional level and the coronary arterial territories. METHODS: LS was measured at baseline before radiotherapy and 6 months post-radiotherapy. The LS was obtained for each myocardial layer (endocardial, mid-myocardial, epicardial), left ventricular regional level (basal, mid, apical) and coronary artery territory (left anterior descending artery (LAD), circumflex artery, right coronary artery). RESULTS: The study included 64 left-sided BC patients. Mean age was 58 years, mean doses to the heart, the left ventricle and the LAD were respectively 3.0, 6.7 and 16.4 Gy. The absolute decrease of LS was significant for the three layers (endocardial: - 20.0 ± 3.2% to - 18.8 ± 3.8%; mid-myocardial: - 16.0 ± 2.7% to - 15.0 ± 3.1%; epicardial: - 12.3 ± 2.5% to - 11.4 ± 2.8%, all p = 0.02), but only the relative decrease of LS in the endocardial layer was close to be significant (- 4.7%, p = 0.05). More precisely, the LS of the endocardial layer was significantly decreased for the most exposed parts of the left ventricle corresponding to the apical level (- 26.3 ± 6.0% vs. -24.2 ± 7.1%, p = 0.03) and LAD territory (- 22.8 ± 4.0% vs. -21.4 ± 4.8%, p = 0.03). CONCLUSION: Six months post-radiotherapy, LS decreased predominantly in the endocardial layer of the most exposed part of the left ventricle. For precise evaluation of radiotherapy-induced cardiotoxicity and early left ventricular dysfunction, the endocardial layer-based LS might be the most sensitive parameter. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605512 , Registered 6 November 2015 - Retrospectively registered.

Telemonitoring versus standard care in heart failure: a randomised multicentre trial.

AIMS: The aim was to assess the effect of a telemonitoring programme vs. standard care (SC) in preventing all-cause deaths or unplanned hospitalisations in heart failure (HF) at 18 months. METHODS AND RESULTS: OSICAT was a randomised, multicentre, open-label French study in 937 patients hospitalised for acute HF ≤12 months before inclusion. Patients were randomised to telemonitoring (daily body weight measurement, daily recording of HF symptoms, and personalised education) (n = 482) or to SC (n = 455). Mean ± standard deviation number of events for the primary outcome was 1.30 ± 1.85 for telemonitoring and 1.46 ± 1.98 for SC [rate ratio 0.97, 95% confidence interval (CI) 0.77-1.23; P = 0.80]. In New York Heart Association (NYHA) class III or IV HF, median time to all-cause death or first unplanned hospitalisation was 82 days in the telemonitoring group and 67 days in the SC group (P = 0.03). After adjustment for known predictive factors, telemonitoring was associated with a 21% relative risk reduction in first unplanned hospitalisation for HF [hazard ratio (HR) 0.79, 95% CI 0.62-0.99; P = 0.044); the relative risk reduction was 29% in patients with NYHA class III or IV HF (HR 0.71, 95% CI 0.53-0.95; P = 0.02), 38% in socially isolated patients (HR 0.62, 95% CI 0.39-0.98; P = 0.043), and 37% in patients who were ≥70% adherent to body weight measurement (HR 0.63, 95% CI 0.45-0.88; P = 0.006). CONCLUSION: Telemonitoring did not result in a significantly lower rate of all-cause deaths or unplanned hospitalisations in HF patients. The pre-specified subgroup results suggest the telemonitoring approach improves clinical outcomes in selected populations but need further confirmation.

Early detection of subclinical left ventricular dysfunction after breast cancer radiation therapy using speckle-tracking echocardiography: association between cardiac exposure and longitudinal strain reduction (BACCARAT study).

BACKGROUND: Breast cancer (BC) radiotherapy (RT) can induce cardiotoxicity, with adverse events often observed many years after BC RT. Subclinical left ventricular (LV) dysfunction can be detected early after BC RT with global longitudinal strain (GLS) measurement based on 2D speckle-tracking echocardiography. This 6-month follow-up analysis from the BACCARAT prospective study aimed to investigate the association between cardiac radiation doses and subclinical LV dysfunction based on GLS reduction. METHODS: The patient study group consisted of 79 BC patients (64 left-sided BC, 15 right-sided BC) treated with RT without chemotherapy. Echocardiographic parameters, including GLS, were measured before RT and 6 months post-RT. The association between subclinical LV dysfunction, defined as GLS reduction > 10%, and radiation doses to whole heart and the LV were performed based on logistic regressions. Non-radiation factors associated with subclinical LV dysfunction including age, BMI, hypertension, hypercholesterolemia and endocrine therapy were considered for multivariate analyses. RESULTS: A mean decrease of 6% in GLS was observed (- 15.1% ± 3.2% at 6 months vs. - 16.1% ± 2.7% before RT, p = 0.01). For left-sided patients, mean heart and LV doses were 3.1 ± 1.3 Gy and 6.7 ± 3.4 Gy respectively. For right-sided patients, mean heart dose was 0.7 ± 0.5 Gy and median LV dose was 0.1 Gy. Associations between GLS reduction > 10% (37 patients) and mean doses to the heart and the LV as well as the V20 were observed in univariate analysis (Odds Ratio = 1.37[1.01-1.86], p = 0.04 for Dmean Heart; OR = 1.14 [1.01-1.28], p = 0.03 for Dmean LV; OR = 1.08 [1.01-1.14], p = 0.02 for LV V20). In multivariate analysis, these associations did not remain significant after adjustment for non-radiation factors. Further exploratory analysis allowed identifying a subgroup of patients (LV V20 > 15%) for whom a significant association with subclinical LV dysfunction was found (adjusted OR = 3.97 [1.01-15.70], p = 0.048). CONCLUSIONS: This analysis indicated that subclinical LV dysfunction defined as a GLS decrease > 10% is associated with cardiac doses, but adjustment for non-radiation factors such as endocrine therapy lead to no longer statistically significant relationships. However, LV dosimetry may be promising to identify high-risk subpopulations. Larger and longer follow-up studies are required to further investigate these associations. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605512, Registered 6 November 2015 - Retrospectively registered.

Early detection and prediction of cardiotoxicity after radiation therapy for breast cancer: the BACCARAT prospective cohort study.

BACKGROUND: Radiotherapy (RT) for breast cancer presents a benefit in terms of reducing local recurrence and deaths resulting from breast cancer but it can lead to secondary effects due to the presence of neighboring cardiac normal tissues within the irradiation field. Breast RT has been shown to be associated with long-term increased risk of heart failure, coronary artery disease, myocardial infarction and finally cardiovascular death more than 10 years after RT. However, there is still a lack of knowledge for early cardiotoxicity induced by breast RT that can appear long before the onset of clinically significant cardiac events. Based on a 2-year follow-up prospective cohort of patients treated with breast RT, the BACCARAT (BreAst Cancer and CArdiotoxicity Induced by RAdioTherapy) study aims to enhance knowledge on detection and prediction of early subclinical cardiac dysfunction and lesions induced by breast RT and on biological mechanisms potentially involved, based on functional and anatomical cardiac imaging combined with simultaneous assessment of multiple circulating biomarkers and accurate heart dosimetry. METHODS/DESIGN: BACCARAT study consists in a monocentric prospective cohort study that will finally include 120 women treated with adjuvant 3D CRT for breast cancer, and followed for 2 years after RT. Women aged 50 to 70 years, treated for breast cancer and for whom adjuvant 3D CRT is indicated, without chemotherapy are eligible for the study. Baseline (before RT) and follow-up data include measurements of functional myocardial dysfunction including strain and strain rate based on 2D-speckle tracking echocardiography, anatomical coronary lesions including description of plaques in segments of coronary arteries based on Coronary computed tomography angiography, and a wide panel of circulating biomarkers. The absorbed dose is evaluated for the whole heart and its substructures, in particular the coronary arteries. Analysis on occurrence and evolution of subclinical cardiac lesions and biomarkers will be performed and completed with dose-response relationship. Multivariate model of normal tissue complication probability (NTCP) will also be proposed. DISCUSSION: Tools and results developed in the BACCARAT study should allow improving prediction and prevention of potential lesions to cardiac normal tissues surrounding tumors and ultimately enhance patients' care and quality of life. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02605512.

Early hemodynamic changes versus peak values: what is more useful to predict occurrence of dyspnea during stress echocardiography in patients with asymptomatic mitral stenosis?

BACKGROUND: In asymptomatic mitral stenosis (MS), the usefulness of peak exercise Doppler echocardiography (DE) values is acknowledged, but the role of values recorded during the first stage of DE remains unclear. METHODS: DE was analyzed in 48 asymptomatic patients with significant MS and revealed dyspnea in 22 patients (46%). RESULTS: MS severity and rest and peak systolic pulmonary artery pressures (SPAPs) were not different between patients who did and did not develop dyspnea. Progressions of mean gradient and relative SPAP (ratio of SPAP/baseline SPAP) were significantly greater in patients who developed dyspnea compared with those who did not (P < .01), whereas no difference was observed for absolute SPAP progression (P = .28). Onset of dyspnea was associated with a high increase of relative SPAP (>90% at 60W, OR 2.31; CI, 1.2-4.8; P = .02) but not with the 60 mm Hg peak SPAP threshold (OR 1.3; CI, 0.7-43.1; P = .40). CONCLUSION: DE reveals symptoms in 46% of patients who are considered asymptomatic. Despite similar peak values, these patients have different hemodynamic parameters during the first level of exercise compared with patients remaining asymptomatic. This may lead to the integration of early hemodynamic changes in the evaluation of exercise tolerance.

[Stress cardiomyopathy, a topical cardiac disorder]. / Les cardiomyopathies de stress, une pathologie cardiaque d'actualité.

Stress cardiomyopathy (Tako-Tsubo, Broken Heart syndrome, or apical ballooning syndrome) was recently recognized as a distinct clinical entity. The aims of this review are to define this acute and reversible cardiomyopathy and to list its major clinical, biological and angiographic features. We performed a Medline scan for all relevant case series. The studies thus identified suggest that the apical ballooning syndrome accounts for 2% of ST-elevation infarcts, mainly affects women, and occurs after major emotional or physical stress. Most patients present with chest pain and dyspnoea, cardiogenic shock and (or?) ventricular fibrillation. ST segment modifications and mildly elevated cardiac enzyme levels are reported in 81% of patients. Left ventricular dysfunction occurs in the absence of epicardial coronary artery obstruction and typically consists of a hyperkinetic basal region and an akinetic apical half of the ventricle. The in-hospital mortality rate is about 1.2%. Most patients recover fully after a few weeks. Norepinephrine concentrations are elevated in three-quarters of patients. This syndrome should be considered among the differential diagnoses in patients presenting with chest pain, and especially in post-menopausal women with a recent history of stress. In its broadest sense, this phenomenon may encompass a range of disorders, including left ventricular dysfunction following central nervous system injury. It should also be considered in women with acute coronary syndromes.

Echocardiographic evaluation of the mitral valve area before and after percutaneous mitral commissurotomy: the pressure half-time method revisited.

BACKGROUND: Doppler pressure half-time (PHT) is widely used for mitral valve area (MVA) assessment but its accuracy has not been fully evaluated before and after percutaneous mitral commissurotomy (PMC) in a large series of patients. METHODS: In 120 patients with severe mitral stenosis, MVA(PHT) was prospectively evaluated before and 24 to 48 hours after PMC and compared with 2-dimensional planimetry (MVA(2D)) as a reference method. RESULTS: After PMC, MVA(2D) significantly increased (1.81 +/- 0.30 vs 1.03 +/- 0.23 cm2, P < .0001), mean transmitral gradient decreased (5 +/- 3 vs 10 +/- 5 mm Hg, P < .0001), and a good valve opening (MVA(2D) > or = 1.5 cm2) was observed in 107 patients (89%). Before PMC, correlation between MVA(PHT) and MVA(2D) was only fair overall (r = 0.52, P < .0001) and weak in subgroups of older patients (> or = 60 years; r = 0.16, P = .37) and in patients in atrial fibrillation (r = 0.38, P < .05). After PMC, MVA(PHT) (1.62 +/- 0.39 cm2) was significantly lower than MVA(2D) (P < .0001) and correlation was poor overall (r = 0.30, P = .0004; mean difference 0.33 +/- 0.30 cm2) and in all subgroups (r < 0.35). However, for the prediction of a good valve opening, a PHT less than 130 milliseconds (observed in 43 patients, 36%) had an excellent specificity (100%) despite a poor sensitivity (44%). CONCLUSION: For MVA assessment, the PHT method should be used cautiously even before PMC, especially in older patients or those in atrial fibrillation. After PMC, it does not provide an accurate MVA evaluation but can still be used as a semiquantitative method: a PHT less than 130 milliseconds is associated with a good valve opening, which can be useful in difficult cases.

Extracellular matrix remodelling in human aortic valve disease: the role of matrix metalloproteinases and their tissue inhibitors.

AIMS: Aortic valve diseases are characterized by pathological remodelling of valvular tissue but the cellular and molecular effectors involved in these processes are not well known. The role of matrix metalloproteinase (MMP)-2, MMP-9, MMP-3, MMP-7, and tissue inhibitor of matrix metalloproteinase (TIMP)-1 and TIMP-2 are investigated here. METHODS AND RESULTS: Histological analysis of pathological valves [aortic stenosis (AS) (n=49), aortic regurgitation (AR) (n=23)] and control valves (n=8) was performed. The main tissue abnormalities (calcification, inflammatory cells, and capillaries) observed in AS were less severe or absent in AR. However, both groups of pathological valves displayed similar histological signs of extracellular matrix (ECM) remodelling. Biochemical analysis of MMPs and TIMPs (gelatin and casein zymography and ELISA) was performed on valve extracts. MMP-2 activity was not significantly different in control and pathological valves. Increases in MMP-9 and MMP-3 in AS demonstrated an inflammatory state. Finally, there was a four- to seven-fold increase of TIMP-1 in pathological valves. TIMP-1, TIMP-2, and MMP-2 were synthesized by the valvular interstitial cells in primary culture. CONCLUSION: This study demonstrates the involvement of the MMP/TIMP system in ECM remodelling of both AS and AR. These findings provide evidence of inflammatory injury more severe in AS than in AR and involvement of mesenchymal cell response.

Temporal trends in percutaneous mitral commissurotomy over a 15-year period.

AIMS: To evaluate temporal trends in percutaneous mitral commissurotomy (PMC) in terms of changes in patient characteristics and their impact on immediate results. METHODS AND RESULTS: From 1986 to 2001, PMC was indicated in 2773 consecutive patients. Patient characteristics and results were compared each year and linear trends were analysed. There were significant trends toward an increase in mean age (p <0.0001) and the proportion of patients in NYHA class I or II before PMC (p <0.0001), and toward a decrease in the proportion of atrial fibrillation (p <0.0002) and favourable valve anatomy (p < 0.0001), but no change in initial valve area ( p < 0.22). Technical failure occurred in 32 patients (1.2%). The failure rate decreased from 6.4% in 1986-1987 to 3.6% in 1988 and was less than 1.5% from then on (p < 0.0001). The frequency of good immediate results (valve area > or =1.5 cm(2) without regurgitation >2/4) did not differ over the years ( p < 0.22), with a mean rate of 89.5% of effective procedures and 88.5% of all procedures. CONCLUSION: Over this 15-year period, candidates for PMC became older and had a less favourable anatomy, but underwent PMC at an earlier functional stage. The stability of the results, despite the less favourable characteristics, may be related to the role of experience in improving the technique and patient selection.

Contemporary results of mitral valve repair for infective endocarditis.

OBJECTIVES: We sought to evaluate the feasibility and immediate and late results of mitral valve repair (MVRep) for acute and healed endocarditis. BACKGROUND: Improvements in techniques of MVRep have extended its feasibility in complex lesions, but experience with endocarditis is limited. METHODS: Among 78 patients operated on for mitral endocarditis between 1990 and 1999, 63 underwent MVRep. The repair was performed for acute endocarditis in 25 patients (40%) at a median of 20 days after the onset of treatment and in 38 patients (60%) for healed endocarditis after a median of 11 months. RESULTS: Repair of the mitral valve was feasible in 63 patients (81%). This repair involved annuloplasty in 61 patients (97%), valve resection in 49 (78%), shortening or transposition of chordae in 29 (46%), suture of perforation in 18 (29%), a pericardial patch in 12 (19%), and a partial mitral homograft in 7 (11%). Associated procedures were aortic valve replacement in 11 patients, bypass grafting in 3, and tricuspid repair in 2. Early complications were two deaths (3.2%), one re-operation for severe mitral regurgitation and one re-operation for subsequent aortic endocarditis. The seven-year rate of event-free survival was 78 +/- 6% in the global series. Multivariate predictors of event-free survival were hypertension (p < 0.006) and intervention for acute endocarditis (p < 0.026). Five-year survival rates were 96 +/- 4% after MVRep for acute endocarditis and 91 +/- 5% for healed endocarditis. CONCLUSIONS: Mitral valve repair is frequently feasible and gives good results in patients with infective endocarditis. Patients operated on for acute endocarditis experience more events during follow-up than those operated on after healed endocarditis but have excellent late survival.