Screening for precapillary pulmonary hypertension in chronic myeloproliferative disorders: the role of N-terminal pro-B-type natriuretic peptide and vascular endothelial growth factor - a pilot study.

INTRODUCTION: Precapillary pulmonary hypertension (PH) implies a worse prognosis in myeloproliferative neoplasms (MPN). N-terminal pro-B-type natriuretic peptide (NT-proBNP) is elevated in cardiopulmonary involvement. In MPN patients with precapillary PH, elevated vascular endothelial growth factor (VEGF) values, but in left heart (LH) disease patients, decreased values were reported. Our aim was to determine whether a combination of NT-proBNP and VEGF is suitable for the detection of the precapillary forms of PH in MPN patients. MATERIAL AND METHODS: Eighty-one MPN patients were investigated. Pulmonary hypertension was defined as Doppler-derived systolic pulmonary artery pressure (sPAP) ≥ 40 mm Hg. Patient groups with cardiopulmonary involvement (precapillary PH, PH due to LH disease, left ventricular ejection fraction < 50%, atrial fibrillation) or LH disease (PH due to LH disease, left ventricular ejection fraction < 50%, atrial fibrillation) were identified. RESULTS: In 9 patients PH was associated with LH disease. In 2 patients precapillary PH was found with extremely high NT-proBNP values. NT-proBNP significantly correlated with sPAP (r = 0.550; p < 0.001). NT-proBNP ≥ 466 pg/ml was the best predictor of cardiopulmonary involvement (AUC: 0.962, sensitivity: 86.7%, specificity: 93.9%). No correlation was found between VEGF levels and sPAP values. VEGF ≤ 431 pg/ml was the best predictor of LH disease (AUC: 0.609, sensitivity: 76.9%, specificity: 62.7%). CONCLUSIONS: NT-proBNP levels reflect cardiopulmonary involvement with high accuracy, but the combination of NT-proBNP and VEGF is not suitable for the detection of precapillary PH as the diagnostic power of VEGF is limited. Highly elevated NT-proBNP levels may suggest precapillary PH but further investigation is necessary for the exclusion of LH disease or atrial fibrillation.

Five-year follow-up of left ventricular diastolic function in systemic sclerosis patients: determinants of mortality and disease progression.

OBJECTIVES: In systemic sclerosis (SSc), left ventricular diastolic dysfunction reflects primary myocardial involvement of the disease. We aimed to assess the abnormalities of the diastolic function, analyze the characteristics of the disease progression, and investigate the prognostic value of diastolic dysfunction in SSc patients. PATIENTS AND METHODS: A total of 34 SSc patients (57 ± 12 years, 31 female) were involved in the study. The following traditional or tissue Doppler parameters of left ventricular diastolic function were obtained: E/A, lateral E', E/E', left ventricular mass index (LVM index), and maximal left atrial (LA) volume index. Measurements were repeated after 5.5 years. RESULTS: At baseline, diastolic dysfunction was found in 62% of the SSc patients. Follow-up time was 5.4 ± 1.2 years. A total of 6 patients died of heart failure. In univariate Cox regression analysis, age (HR = 1.08, p < 0.05), LVM index (HR = 1.07, p < 0.01), lateral E' (HR = 1.57, p = 0.05), and LA volume index (HR = 1.11, p < 0.01) were predictors of survival. During the follow-up, significant increase in LA volume index (27.5 ± 9.7 vs. 35.4 ± 10.6 cm(3)/m(2), p < 0.001) and E/E' was found (7.6 ± 2.5 vs. 8.7 ± 3.8, p < 0.05) while E' did not change (9.6 ± 2.6 vs. 9.2 ± 1.9 cm/s, NS). The increase in LA volume index showed positive correlation (r = 0.46, p < 0.05) while the decrease in E' values showed negative correlation (r = -0.54, p < 0.01) with the duration of the SSc. CONCLUSION: In SSc patients, left ventricular diastolic dysfunction is highly prevalent and is associated with increased risk of mortality. Our data suggest that in the advanced phase of the disease, the myocardial fibrotic processes burns out while the increase of the filling pressure progresses continuously.

Impact of cardiac involvement on the risk of mortality among patients with systemic sclerosis: a 5-year follow-up of a single-center cohort.

Cardiac involvement is among the leading causes of mortality in patients with systemic sclerosis (SSc). Previously, we demonstrated in a single-center, cross-sectional study the frequent coexistence of different forms of cardiac involvement in systemic sclerosis including pulmonary arterial hypertension (PAH), coronary artery disease (CAD), and microvascular dysfunction (MVD). The aim of the present study was to investigate the prognostic significance of cardiac involvement. One hundred twenty patients with SSc were enrolled. All cases underwent a non-invasive cardiovascular protocol. In 30 patients with suspected cardiac involvement, right heart catheterization and intra-coronary pressure-wire-supplemented coronary angiography were performed. Clinical follow-up was 5 years. Patients with CAD at the baseline showed a trend for higher cardiovascular mortality while in patients with MVD this difference was significant (26.7 % versus 9.5 %, p = 0.077 and 30 % versus 10.1 %, p < 0.05, respectively). Cardiovascular mortality of PAH cases was higher but, however, did not reach statistical significance 21.4 % versus 10.4 %, p = 0.261. Cardiovascular event-free survival was significantly lower among patients with combinations of two or three disorders (p < 0.05). Multivariate analysis of organ involvements and comorbidities showed that the diffuse cutaneous subset, the presence of kidney involvement, the velocity of the tricuspid regurgitation, as well as diabetes mellitus were independent predictors of overall mortality. MVD and CAD alone or in combination with PAH significantly affected the 5-year cardiovascular mortality. These findings highlight the prognostic importance of coronary disease in patients with SSc [ www.clinicaltrials.gov (Reg. Nr.: NCT00843102)].

The impact of cardiopulmonary manifestations on the mortality of SSc: a systematic review and meta-analysis of observational studies.

OBJECTIVES: Internal organ involvement reduces the life expectancy of SSc patients. Cardiopulmonary manifestations are currently the primary cause of death. We aimed to perform a systematic review and meta-analysis to define more precise effect estimates of different cardiopulmonary manifestations and to verify trends in the mortality of SSc. METHODS: A systematic literature search was performed to identify relevant cohort studies. Reports analyzing the role of the organ manifestations in mortality or analysing survival compared with the control population were included. The outcome parameters were pooled with the random-effect model via generic inverse-variance weighting in conventional and cumulative meta-analysis. RESULTS: Eighteen studies comprising a total of 12, 829 patients qualified. The reported causes of death were as follows: 19.7% cardiac, 16.8% interstitial pulmonary disease, 13.1% pulmonary hypertension and 13.8% renal disease. The risk of death was significantly increased in patients with cardiac involvement [hazard ratio (HR) 3.15], with pulmonary interstitial disease (HR 2.58), with pulmonary hypertension (HR 3.50) and with renal manifestations (HR 2.76). A trend for survival improvement (R2)= 0.4295, P = 0.04) was found, and the difference in survival between the diffuse and limited scleroderma subgroups was diminishing (R2)= 0.4119. P = 0.02). CONCLUSION: Meta-analysis of observational studies indicates a trend for improvement over the last decades in which the life expectancy of SSc patients approaches that of the general population. A decreasing tendency in the survival differences between the limited and diffuse SSc subgroups was also verified. Internal organ involvements have similarly unfavourable predictive impact on survival.