Evaluation of right ventricular dysfunction by myocardial strain echocardiography in patients with intestinal carcinoid disease.

BACKGROUND: Cardiac fibrosis is an important complication of intestinal carcinoid disease, with resulting valvular and ventricular dysfunction due to endocardial fibrosis. Evaluation of right ventricular (RV) function in these patients has focused on valvular involvement. The aim of this study was to investigate whether myocardial strain by echocardiography can detect RV dysfunction in patients with carcinoid disease. METHODS: Eighty-nine patients with intestinal carcinoid and 50 healthy individuals were studied. Strain measurements were assessed by speckle-tracking echocardiography. The average of the three lateral RV segments was calculated as RV strain. Left ventricular global strain was calculated from a 16-segment model. RESULTS: Carcinoid heart disease was present in 15 of the 89 patients. RV strain was reduced in patients with carcinoid disease compared with healthy controls (-20.6 ± 5.0% vs -26.9 ± 4.4%, P < .001). RV function by strain was not significantly different in patients with and without carcinoid heart disease (-21.2 ± 5.7% vs -20.5 ± 4.8%, P = .59). Excluding patients with overt carcinoid heart disease, RV strain was reduced in patients with 5-hydroxyindoleacetic acid levels above the normal range compared with those with levels within the normal range (-19.4 ± 5.4 vs -21.6 ± 3.7%, P = .05). CONCLUSIONS: RV function by myocardial strain was reduced in patients with carcinoid disease independently of valvular involvement. This indicates that myocardial strain by echocardiography provides added information about RV function in patients with intestinal carcinoid disease.

Plasma CCN2/connective tissue growth factor is associated with right ventricular dysfunction in patients with neuroendocrine tumors.

BACKGROUND: Carcinoid heart disease, a known complication of neuroendocrine tumors, is characterized by right heart fibrotic lesions. Carcinoid heart disease has traditionally been defined by the degree of valvular involvement. Right ventricular (RV) dysfunction due to mural involvement may also be a manifestation. Connective tissue growth factor (CCN2) is elevated in many fibrotic disorders. Its role in carcinoid heart disease is unknown. We sought to investigate the relationship between plasma CCN2 and valvular and mural involvement in carcinoid heart disease. METHODS: Echocardiography was performed in 69 patients with neuroendocrine tumors. RV function was assessed using tissue Doppler analysis of myocardial systolic strain. Plasma CCN2 was analyzed using an enzyme-linked immunosorbent assay. Mann-Whitney U, Kruskal-Wallis, Chi-squared and Fisher's exact tests were used to compare groups where appropriate. Linear regression was used to evaluate correlation. RESULTS: Mean strain was -21% +/- 5. Thirty-three patients had reduced RV function (strain > -20%, mean -16% +/- 3). Of these, 8 had no or minimal tricuspid and/or pulmonary regurgitation (TR/PR). Thirty-six patients had normal or mildly reduced RV function (strain < or = -20%, mean -25% +/- 3). There was a significant inverse correlation between RV function and plasma CCN2 levels (r = 0.47, p < 0.001). Patients with reduced RV function had higher plasma CCN2 levels than those with normal or mildly reduced RV function (p < 0.001). Plasma CCN2 > or = 77 microg/L was an independent predictor of reduced RV function (odds ratio 15.36 [95% CI 4.15;56.86]) and had 88% sensitivity and 69% specificity for its detection (p < 0.001). Plasma CCN2 was elevated in patients with mild or greater TR/PR compared to those with no or minimal TR/PR (p = 0.008), with the highest levels seen in moderate to severe TR/PR (p = 0.03). CONCLUSIONS: Elevated plasma CCN2 levels are associated with RV dysfunction and valvular regurgitation in NET patients. CCN2 may play a role in neuroendocrine tumor-related cardiac fibrosis and may serve as a marker of its earliest stages.