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.

Left Ventricular Diastolic Dysfunction Predicts Mortality in Patients With Systemic Sclerosis.

BACKGROUND: Primary cardiac affection is common and is a major cause of death in systemic sclerosis (SSc), but there are knowledge gaps regarding the effect of cardiac dysfunction on mortality. OBJECTIVES: The purpose of this study was to evaluate diastolic function in a large, unselected SSc cohort and assess the effect of diastolic dysfunction (DD) on mortality. METHODS: SSc patients followed prospectively at the Oslo University Hospital from 2003 to 2016 with available echocardiographies and matched control subjects were included. DD was assessed by echocardiography according to the 2016 American Society of Echocardiography/European Association of Cardiovascular Imaging guidelines. Pulmonary hypertension (PH) was diagnosed by right heart catheterization. Vital status was available for all patients. Cox regression analyses with hazards ratios (HRs) were conducted. RESULTS: Diastolic function was assessed in 275 SSc patients at baseline and in 186 patients at follow-up. At baseline, 46 of the 275 SSc patients (17%) were diagnosed with DD and 195 (71%) had normal diastolic function. After a median follow-up of 3.4 years (interquartile range: 1.6 to 6.2 years), the proportion of DD increased from 17% to 29%. During follow-up, 57% of patients with DD at baseline died, compared with 13% of patients with normal diastolic function. At baseline, 86 patients had performed right heart catheterization, and 43 were diagnosed with PH; of these 60% deceased. In multivariable Cox regression analyses, DD was a stronger predictor of death (HR: 3.7; 95% CI: 1.69 to 8.14; c-index 0.89) than PH (HR: 2.0; 95% CI: 1.1 to 3.9; c-index 0.84). CONCLUSIONS: DD is frequent in SSc, and the presence of DD is associated with high mortality. DD exceeds PH with respect to predicting mortality.

Morbidity outcomes after surgical aortic valve replacement.

OBJECTIVE: In patients with mild to moderate operative risk, surgical aortic valve replacement (SAVR) is still the preferred treatment for patients with severe symptomatic aortic stenosis (AS). Aiming to broaden the knowledge of postsurgical outcomes, this study reports a broad set of morbidity outcomes following surgical intervention. METHODS: Our cohort comprised 442 patients referred for severe AS; 351 had undergone SAVR, with the remainder (91) not operated on. All patients were evaluated using the 6-minute walk test (6MWT), were assigned a New York Heart Association class (NYHA) and Canadian Cardiovascular Society class (CCS), with additional scores for health-related quality of life (HRQoL), cognitive function (Mini-Mental State Examination (MMSE)) and myocardial remodelling (at inclusion and at 1-year follow-up). Adverse events and mortality were recorded. RESULTS: Three-year survival after SAVR was 90.0%. SAVR was associated with an improved NYHA class, CCS score and HRQoL, and provoked reverse ventricular remodelling. The 6MWT decreased, while the risks of major adverse cardiovascular events (death, non-fatal stroke/transient ischaemic attack or myocardial infarction) and all-cause hospitalisation (incidence rate per 100 patient-years) were 13.5 and 62.4, respectively. The proportion of cognitive disability measured by MMSE increased after SAVR from 3.2% to 8.8% (p=0.005). Proportion of patients living independently at home, having attained NYHA class I, was met by 49.1% at 1 year. Unoperated individuals had a poor prognosis in terms of any outcome. CONCLUSION: This study provides knowledge of outcomes beyond what is known about the mortality benefit after SAVR to provide insight into the morbidity burden of modern-day SAVR.

Echocardiographic evidence of right ventricular functional improvement after balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension.

BACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) induces right ventricular (RV) adaptive changes but often results in RV failure and death. Balloon pulmonary angioplasty (BPA) is a treatment option in patients in whom pulmonary endarterectomy is contraindicated and in patients with residual pulmonary hypertension after pulmonary endarterectomy. We hypothesized that RV reverse remodeling and improved RV function would occur after BPA in patients with CTEPH. METHODS: In 26 patients with CTEPH (59 ± 12 years old; 11 men), echocardiography, cardiopulmonary exercise testing, blood samples, and right-sided cardiac catheterization were performed before and after 4 ± 2 BPA procedures. Echocardiography images were analyzed off-line with particular focus on RV function according to current recommendations. Differences from baseline to follow-up were analyzed by paired samples t tests. RESULTS: Significant improvements in hemodynamics, peak oxygen consumption, and levels of N-terminal pro-B-type natriuretic peptide were detected after BPA. All measures of RV function improved considerably, including fractional area change (+6%; p = 0.003), tricuspid annular plane systolic excursion (+3 mm; p < 0.001), and RV free wall peak strain (-4.4; p = 0.002). RV end-diastolic diameter, area, and free wall thickness decreased significantly, whereas left ventricular diameter and stroke volume increased. CONCLUSIONS: After BPA, a significant improvement in RV functional parameters could be observed by echocardiography, adding credibility to this form of treatment in patients with CTEPH.

The effect of rosuvastatin on inflammation, matrix turnover and left ventricular remodeling in dilated cardiomyopathy: a randomized, controlled trial.

BACKGROUND: Dilated cardiomyopathy is characterized by left ventricular dilatation and dysfunction. Inflammation and adverse remodeling of the extracellular matrix may be involved in the pathogenesis. Statins reduce levels of low density lipoprotein cholesterol, but may also attenuate inflammation and affect matrix remodeling. We hypothesized that treatment with rosuvastatin would reduce or even reverse left ventricular remodeling in dilated cardiomyopathy. MATERIALS AND METHODS: In this multicenter, randomized, double blind, placebo-controlled study, 71 patients were randomized to 10 mg of rosuvastatin or matching placebo. Physical examination, blood sampling, echocardiography and cardiac magnetic resonance imaging were performed at baseline and at six months' follow-up. The pre-specified primary end point was the change in left ventricular ejection fraction from baseline to six months. RESULTS: Over all, left ventricular ejection fraction improved 5 percentage points over the duration of the study, but there was no difference in the change in left ventricular ejection fraction between patients allocated to rosuvastatin and those allocated to placebo. Whereas serum low density lipoprotein cholesterol concentration fell significantly in the treatment arm, rosuvastatin did not affect plasma or serum levels of a wide range of inflammatory variables, including C-reactive protein. The effect on markers of extracellular matrix remodeling was modest. CONCLUSION: Treatment with rosuvastatin does not improve left ventricular ejection fraction in patients with dilated cardiomyopathy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00505154.

Prognostic value of circulating microRNA-210 levels in patients with moderate to severe aortic stenosis.

BACKGROUND: Circulating micro-RNAs have been proposed as a novel class of cardiovascular (CV) biomarkers, but whether they meet analytical requirements and provide additional information to establish risk indices have not been established. miR-210 levels are increased in subjects with low VO2 max, which is a recognized risk factor in patients with aortic stenosis (AS), and we hypothesized that circulating miR-210 levels may be increased in patients with AS and associated with a poor prognosis. METHODS: We measured circulating miR-210 levels by real-time PCR in 57 patients with moderate to severe AS and in 10 age- and gender-matched healthy controls. The merit of miR-210 as a biomarker was assessed according to established criteria, including by comparing miR-210 levels with NT-proBNP and miR-22 levels, which is another miRNA biomarker candidate. RESULTS: All patients and control subjects had miR-210 levels within the range of detection (Cq<35) and the analytical variability was low. Circulating miR-210 levels were 2.0±0.2 [mean±SEM] fold increased in AS patients compared to controls (p = 0.002), whereas miR-22 levels were not differently expressed in the AS patients (0.12±0.06 fold increase, p = 0.45). The increase in miR-210 levels in AS patients was comparable to the increment in NT-proBNP levels: [AUC] 0.82 (95% CI 0.70-0.90) vs. 0.85 (0.75-0.93), respectively, p = 0.71. During a median follow-up of 1287 days, 15 patients (26%) died. There was a significant association between higher circulating levels of miR-210 and increased mortality during follow-up: hazard ratio [supra- vs. inframedian levels] 3.3 (95% CI 1.1-10.5), p = 0.039. Adjusting for other risk indices in multivariate analysis did not attenuate the prognostic merit of circulating miR-210 levels. CONCLUSION: Circulating miR-210 levels are increased in patients with AS and provide independent prognostic information to established risk indices. Analytical characteristics were also excellent supporting the potential of micro-RNAs as novel CV biomarkers.

Prognostic usefulness of circulating high-sensitivity troponin T in aortic stenosis and relation to echocardiographic indexes of cardiac function and anatomy.

The new high-sensitivity cardiac troponin T (hs-cTnT) assay seems to provide important prognostic information in patients with stable cardiovascular disease. To understand the merit of hs-cTnT more closely in stable cardiovascular disease, we performed extensive echocardiographic characterization of 57 patients with aortic stenosis and myocardial hypertrophy and related hs-cTnT levels to prognosis and echocardiographic indexes of myocardial structure and function. The hs-cTnT levels were above the assay's detection limit in all patients, correlated with echocardiographic indexes of structure and function, most notably with left ventricular mass, and demonstrated prognostic utility of similar strength as N-terminal pro-B-type natriuretic peptide. In conclusion, these findings indicate that hs-cTnT may provide prognostic information in patients with aortic stenosis, and that left ventricular mass is an important determinant of TnT levels in stable patients as measured by the new highly sensitive assay.