Systolic dysfunction in systemic sclerosis: Prevalence and prognostic implications

Objective Primary cardiac involvement is presumed to account for a substantial part of disease‐related mortality in systemic sclerosis (SS c). Still, there are knowledge gaps on the evolution and total burden of systolic dysfunction in SS c. Here we evaluated prospective left ventricular (LV ) and right ventricular (RV ) systolic function in an unselected SS c cohort and assessed the burden of systolic dysfunction on mortality. Methods From the Oslo University Hospital cohort, 277 SS c patients were included from 2003‐2016 and compared with healthy controls. Serial echocardiographies were reevaluated in order to detect change in systolic function. Right heart catheterization was performed on patients suspected of pulmonary hypertension. Descriptive and regression analyses were conducted. Results At baseline, LV systolic dysfunction by ejection fraction less than 50%, or a global longitudinal strain greater than −17.0%, was found in 12% and 24%, respectively. RV systolic dysfunction measured by tricuspid annular plane systolic excursion (TAPSE ) less than 17 mm was evident in 10%. Follow‐up echocardiography was performed after a median of 3.3 years (interquartile range [IQR ] 1.5‐5.6). At follow‐up, LV systolic function remained stable, whereas RV function evaluated by TAPSE deteriorated (mean 23.1 to 21.7 mm, P = 0.005) equaling a 15% prevalence of RV systolic dysfunction. RV systolic function predicted mortality in multivariable models (hazard ratio 0.41, 95% confidence interval [CI ] 0.19‐0.90, P value 0.027), whereas LV systolic function lost predictive significance when adjusted for TAPSE . Conclusion In this unselected and prospective study, systolic dysfunction of the LV and RV was a frequent complication of SS c. LV systolic function remained stable across the observation period, whereas RV function deteriorated and predicted mortality

Systolic dysfunction in systemic sclerosis: Prevalence and prognostic implications

Objective Primary cardiac involvement is presumed to account for a substantial part of disease‐related mortality in systemic sclerosis (SSc). Still, there are knowledge gaps on the evolution and total burden of systolic dysfunction in SSc. Here we evaluated prospective left ventricular (LV) and right ventricular (RV) systolic function in an unselected SSc cohort and assessed the burden of systolic dysfunction on mortality. Methods From the Oslo University Hospital cohort, 277 SSc patients were included from 2003‐2016 and compared with healthy controls. Serial echocardiographies were reevaluated in order to detect change in systolic function. Right heart catheterization was performed on patients suspected of pulmonary hypertension. Descriptive and regression analyses were conducted. Results At baseline, LV systolic dysfunction by ejection fraction less than 50%, or a global longitudinal strain greater than −17.0%, was found in 12% and 24%, respectively. RV systolic dysfunction measured by tricuspid annular plane systolic excursion (TAPSE) less than 17 mm was evident in 10%. Follow‐up echocardiography was performed after a median of 3.3 years (interquartile range [IQR] 1.5‐5.6). At follow‐up, LV systolic function remained stable, whereas RV function evaluated by TAPSE deteriorated (mean 23.1 to 21.7 mm, P = 0.005) equaling a 15% prevalence of RV systolic dysfunction. RV systolic function predicted mortality in multivariable models (hazard ratio 0.41, 95% confidence interval [CI] 0.19‐0.90, P value 0.027), whereas LV systolic function lost predictive significance when adjusted for TAPSE. Conclusion In this unselected and prospective study, systolic dysfunction of the LV and RV was a frequent complication of SSc. LV systolic function remained stable across the observation period, whereas RV function deteriorated and predicted mortality

Incremental Value of Myocardial Work over Global Longitudinal Strain in the Surveillance for Cancer-Treatment-Related Cardiac Dysfunction: A Case–Control Study

The load dependence of global longitudinal strain (GLS) means that changes in systolic blood pressure (BP) between visits may confound the diagnosis of cancer-treatment-related cardiac dysfunction (CTRCD). We sought to determine whether the estimation of myocardial work, which incorporates SBP, could overcome this limitation. In this case–control study, 44 asymptomatic patients at risk of CTRCD underwent echocardiography at baseline and after oncologic treatment. CTRCD was defined on the basis of the change in the ejection fraction. Those with CTRCD were divided into subsets with and without a follow-up SBP increment >20 mmHg (CTRCD+BP+ and CTRCD+BP−), and matched with patients without CTRCD (CTRCD-BP+ and CTRCD-BP-). The work index (GWI), constructive work (GCW), wasted work (GWW), and work efficiency (GWE) were assessed in addition to the GLS. The largest increases in the GWI and GCW at follow-up were found in CTRCD-BP+ patients. The CTRCD+BP-patients demonstrated significantly larger decreases in GWI and GCW than their CTRCD+BP+ and CTRCD-BP-peers. ROC analysis for the discrimination of LV functional changes in response to increased afterload in the absence of cardiotoxicity revealed higher AUCs for GCW (AUC = 0.97) and GWI (AUC = 0.93) than GLS (AUC = 0.73), GWW (AUC = 0.51), or GWE (AUC = 0.63, all p-values < 0.001). GCW (OR: 1.021; 95% CI: 1.001–1.042; p < 0.04) was the only feature independently associated with CTRCD-BP+. Myocardial work is superior to GLS in the serial assessments in patients receiving cardiotoxic chemotherapy. The impairment of GLS in the presence of an increase in GWI and GCW indicates the impact of elevated afterload on LV performance in the absence of actual myocardial impairment

Cardioprotection Using Strain-Guided Management of Potentially Cardiotoxic Cancer Therapy: 3-Year Results of the SUCCOUR Trial

Background: Global longitudinal strain (GLS) can predict cancer therapeutics–related cardiac dysfunction and guide initiation of cardioprotection (CPT). Objectives: In this study, the authors sought to determine whether echocardiography GLS-guided CPT provides less cardiac dysfunction in survivors of potentially cardiotoxic chemotherapy, compared with usual care at 3 years. Methods: In this international multicenter prospective randomized controlled trial, patients were enrolled from 28 international sites. All patients treated with anthracyclines with another risk factor for heart failure were randomly allocated to GLS-guided (>12% relative reduction in GLS) or ejection fraction (EF)–guided (>10% absolute reduction of EF to <55%) CPT. The primary end point was the change in 3-dimensional (3D) EF (DEF) from baseline to 3 years. Results: Among 331 patients enrolled, 255 (77%, age 54 12 years, 95% women) completed 3-year follow-up (123 in the EF-guided group and 132 in the GLS-guided group). Most had breast cancer (n ¼ 236; 93%), and anthracycline followed by trastuzumab was the most common chemotherapy regimen (84%). Although 67 (26%) had hypertension and 32 (13%) had diabetes mellitus, left ventricular function was normal at baseline (EF: 59% 6%, GLS: 20.7% 2.3%). CPT was administered in 18 patients (14.6%) in the EF-guided group and 41 (31%) in the GLS-guided group (P ¼ 0.03). Most patients showed recovery in EF and GLS after chemotherapy; 3-year DEF was 0.03% 7.9% in the EF-guided group and 0.02% 6.5% in the GLS-guided (P ¼ 0.99) group; respective 3-year EFs were 58% 6% and 59% 5% (P ¼ 0.06). At 3 years, 17 patients (5%) had cancer therapeutics–related cardiac dysfunction (11 in the EFguided group and 6 in the GLS guided group; P ¼ 0.16); 1 patient in each group was admitted for heart failure. Conclusions: Among patients taking potentially cardiotoxic chemotherapy for cancer, the 3-year data showed improvement of LV dysfunction compared with 1 year, with no difference in DEF between GLS- and EF-guided CPT.Tomoko Negishi ... Mitra Shirazi ... et al

Cardiovascular Parameters to 2 years After Kidney Transplantation Following Early Switch to Everolimus Without Calcineurin Inhibitor Therapy: An Analysis of the Randomized ELEVATE Study

Nephrolog

Rationale and Design of the Strain Surveillance of Chemotherapy for Improving Cardiovascular Outcomes: The SUCCOUR Trial

Objectives: This study sought to evaluate the hypothesis that global longitudinal strain (GLS) guidance of cardioprotective therapy would improve cardiac function of at-risk patients undergoing potentially cardiotoxic chemotherapy, compared with usual care. Background: The conventional criteria for diagnosis of chemotherapy-related cardiac dysfunction (CTRCD) are dependent on the recognition of heart failure symptoms and/or changes in left ventricular ejection fraction. However, the measurement variability of left ventricular ejection fraction necessitates broad diagnostic ranges, with the consequence of low sensitivity for CTRCD. Observational data have shown GLS to be a robust and sensitive marker to predict CTRCD and thereby guide the initiation of cardioprotective therapy, but these data are insufficient to justify changing the diagnostic criteria for CTRCD. Methods: The SUCCOUR (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes) trial is an international multicenter prospective randomized controlled trial. Patients who are taking cardiotoxic chemotherapy (n = 320) with at least 1 risk factor will be randomly allocated into GLS- and ejection fraction–guided strategies. All participants will be followed over 3 years for the primary endpoint (change in 3-dimensional ejection fraction) and other secondary endpoints. Results: Among the first 185 patients (age 54 ± 13 years; 93% women) from 23 international sites, 88% had breast cancer, 9% had lymphoma, and 3% had other cancers. Heart failure risk factors were prevalent: 34% had hypertension and 10% had diabetes mellitus. The most common chemotherapy regimen during this study was the combination of anthracycline and trastuzumab. The baseline 3-dimensional left ventricular ejection fraction was 61 ± 4%, and GLS was 20.3 ± 2.5%. Of 93 patients followed up in the first year of the study, 10 had to withdraw for noncardiac reasons. Of 40 patients randomized to the GLS-guided arm, 15 have been started on cardioprotective therapy, whereas 4 of 46 patients in the ejection fraction–guided arm have been started on therapy. Conclusions: The SUCCOUR trial will be the first randomized controlled trial of GLS and will provide evidence to inform guidelines regarding the place of GLS for surveillance for CTRCD. (Strain sUrveillance of Chemotherapy for improving Cardiovascular Outcomes [SUCCOUR]; ANZ Clinical Trials ACTRN12614000341628