Inês Zimbarra Cabrita

Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary hypertension.

ABSTRACT The authors investigated the safety of oral tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthesis, as a novel treatment for pulmonary hypertension (PH). Eighteen patients with pulmonary arterial hypertension or inoperable chronic thromboembolic PH received sapropterin dihydrochloride (6R-BH4), the optically active form of BH4, in addition to treatment with sildenafil and/or endothelin receptor antagonists in an open-label, dose-escalation study. 6R-BH4 was administered starting at a dose of 2.5 mg/kg and increasing to 20 mg/kg over 8 weeks. Changes in markers of nitric oxide synthesis, inflammation and oxidant stress, as well as exercise capacity and cardiac function were measured. 6R-BH4 was well tolerated at all doses without systemic hypotension, even when given in combination with sildenafil. There was a small but significant reduction in plasma monocyte chemoattractant protein (MCP)-1 levels on 5 mg/kg. No significant changes in measures of nitric oxide synthesis or oxidant stress were observed. There was improvement in 6-minute walk distance, most significant at a dose of 5 mg/kg, from 379 ± 61 to 413 ± 57 m 414 ± 57 m (P = .002). Oral 6R-BH4 can be administered safely in doses up to 20 mg/kg daily to patients with PH. Further studies are needed to explore its therapeutic potential.

Assessment of cardiac valve dysfunction in patients receiving cabergoline treatment for hyperprolactinaemia

Objective  Cabergoline is a highly effective medical treatment for patients with hyperprolactinaemia. There is an increased risk of valvular heart disease in patients receiving cabergoline for Parkinson’s disease. This study examined whether cabergoline treatment of hyperprolactinaemia is associated with a greater prevalence of valvulopathy.

Right ventricular function in patients with pulmonary hypertension; the value of myocardial performance index measured by tissue Doppler imaging

AIMS Myocardial performance index (MPI) measured by conventional Doppler is routinely used to assess right ventricular (RV) systolic function in patients with pulmonary hypertension (PH). Our aim was to determine whether MPI measured by Doppler tissue imaging (tMPI) is effective in assessing RV function in these patients. METHODS AND RESULTS Retrospectively, we have studied 196 patients with chronic PH [pulmonary arterial systolic pressure (PASP) 81 +/- 40 mmHg] and 37 healthy volunteers (PASP of 27 +/- 7 mmHg). According to the exclusion criteria, 172 patients were included in the final study cohort. All patients were evaluated for RV systolic function by different parameters. MPI was measured by both conventional and tissue Doppler imaging. Bland-Altman analysis showed moderate agreement between MPI and tMPI (the mean difference was -0.02, absolute difference = -0.32 to 0.29; 95% intervals of agreement, percentage of average = -46.6 to 40.8%). In 50 consecutive PH patients where additional parameters were calculated, we found a significant correlation between tMPI and RV ejection fraction (r = -0.73, P< 0.0001) and RV fractional area change (r = -0.58, P< 0.0001). No significant inter- and intra-observer variability was identified. CONCLUSION This study demonstrated a moderate agreement between two methods of measuring MPI. A good correlation of tMPI with RV ejection fraction and RV fractional area change was found indicating that tMPI might be superior to MPI Doppler. tMPI is a parameter unaffected by RV geometry and importantly has the advantage of simultaneously recording the time intervals from the same cardiac cycle.

The association between tricuspid regurgitation velocity and 5‐year survival in a North West London population of patients with sickle cell disease in the United Kingdom

Raised tricuspid regurgitant velocity (TRV) occurs in approximately 30% of adults with sickle cell disease (SCD), and has been shown to be an independent risk factor for death. TRV was assessed in 164 SCD patients who were subsequently followed up for survival. Raised pulmonary pressures were defined as a TRV jet ≥2·5 m/s on echocardiography. Elevated TRV was present in 29·1% of patients and it was associated with increased age and left atrial diameter. There were 15 deaths (9·1%) over a median of 68·1 months follow up; seven patients had increased TRV, and eight patients had a TRV<2·5 m/s. Higher TRV values were associated with a greater than 4‐fold increased risk of death (Hazard Ratio: 4·48, 99% confidence interval 1·01‐19·8), although we found a lower overall mortality rate than has been reported in previous studies. TRV was not an independent risk factor for death. We have confirmed the association between raised TRV and mortality in a UK SCD population whose disease severity appears to be less than that reported in previous studies. Further prospective studies are needed to more clearly characterize which patient factors modify survival in SCD patients with raised TRV.

Validation of the isovolumetric relaxation time for the estimation of pulmonary systolic arterial blood pressure in chronic pulmonary hypertension

AIMS Transthoracic echocardiography is a useful technique for non-invasive detection of pulmonary arterial systolic pressure (PASP). Isovolumic relaxation time (IVRT) measured by Doppler tissue imaging (DTI) is a sensitive measurement of changes in pulmonary vasculature. Our aim was to validate IVRT in the echocardiographic assessment of pulmonary hypertension (PH) patients. METHODS AND RESULTS We studied 196 PH patients (67% women, mean age 51.8 ± 16.6 years, mean PASP: 81 ± 24 mmHg) and 37 consecutive age- and sex-matched controls (58% women, mean age 44.7 ± 16.4 years, mean PASP 27.7 ± 5.5 mmHg). The estimation of PASP was derived from tricuspid regurgitation velocity according to the Bernoulli equation. The measurement of IVRT was calculated using pulsed tissue Doppler. In the PH group and in the healthy volunteers group (P < 0.0001), the average IVRT was 113.4 ± 28.5 ms [95% confidence interval (CI): 109-117] and 41 ± 12.5 ms (95% CI: 37-45), respectively. We found a strong correlation between IVRT and systolic pulmonary pressure in the PH group (r = 0.52, P < 0.0001) and a cut-off of 75 ms showed a sensitivity and specificity of 94% and 97%, respectively, for the prediction of elevated PASP. CONCLUSION The determination of IVRT by DTI is a simple and reproducible method that correlates well with PASP. It is, therefore, a parameter to consider in the echocardiographic assessment of patients with PH, and may be particularly important when the tricuspid Doppler signal is poor.

ORIGINAL ARTICLE: Assessment of cardiac valve dysfunction in patients receiving cabergoline treatment for hyperprolactinaemia

Objective  Cabergoline is a highly effective medical treatment for patients with hyperprolactinaemia. There is an increased risk of valvular heart disease in patients receiving cabergoline for Parkinson’s disease. This study examined whether cabergoline treatment of hyperprolactinaemia is associated with a greater prevalence of valvulopathy.

Echocardiographic and Hemodynamic Predictors of Survival in Precapillary Pulmonary Hypertension Seven-Year Follow-Up

Background—In this study, we looked at the prognostic value of echocardiographic and hemodynamic measures in a large cohort of patients with precapillary pulmonary hypertension before and after initiation of treatment. Methods and Results—Data were collected prospectively in a cohort of consecutive patients with precapillary pulmonary hypertension referred between 2002 and 2011. A range of clinical and echocardiographic variables were collected and stored on a database to assess predictors of survival. Invasive hemodynamic data including pulmonary artery pressure, pulmonary vascular resistance, capillary wedge pressure, and cardiac index were also obtained at baseline in all patients. Outcome was defined as mortality because of cardiovascular-related death. The study cohort comprised 777 patients (514 women) with precapillary pulmonary hypertension. A total of 195 (25%) died. In multivariable analysis, moderate or severe tricuspid regurgitation (hazard ratio [HR], 26.537; 95% confidence interval, 11.536–61.044; P<0.001), right ventricular myocardial performance index (HR, 3.421; 95% confidence interval, 1.777–6.584; P<0.001), and the presence of pericardial effusion (HR, 1.38; 95% confidence interval, 1.023–1.862; P=0.035) were independent predictors of mortality. High pulmonary vascular resistance and right atrial pressure by invasive hemodynamic measurements were independent predictors of mortality (HR, 1.084; 95% confidence interval, 1.041–1.130, and 1.079, respectively; 95% confidence interval, 1.049–1.111; P<0.001 for both), whereas patients with a higher cardiac index had better survival overall (HR, 0.384; 95% confidence interval, 0.307–0.481; P<0.001). Conclusions—Right ventricular dysfunction, moderate–severe tricuspid regurgitation, low cardiac index, and raised right atrial pressure were associated with poor survival for both pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertensive disease patients. The severity of tricuspid regurgitation, myocardial performance index, presence of pericardial effusion, pulmonary vascular resistance, cardiac index, and right atrial pressure may be used to stratify risk of death.

Disfunção sistólica ventricular esquerda detetada por speckle tracking em hipertensos com fração de ejeção preservada

INTRODUCTION The spectrum of hypertensive heart disease is wide, and can include left ventricular dysfunction. The development of echocardiographic parameters to improve patient stratification and to identify early adverse changes could be clinically useful. Aim To identify subclinical left ventricular dysfunction in hypertensive subjects with preserved ejection fraction (>55%), identified by global parameters of myocardial strain on speckle tracking imaging. METHODS This was a comparative observational study of two groups of individuals: normotensive (n=20, age 59 ± 7 years, 55% male) and hypertensive (n=229, age 62 ± 12 years, 57% male). Left ventricular function was assessed by various conventional clinical and echocardiographic parameters and global longitudinal and circumferential myocardial strain. Cut-off values to detect subclinical left ventricular dysfunction were established and applied in the hypertensive group. The Students t test, Mann-Whitney test and chi-square test were used for the comparative statistical analysis. RESULTS Most hypertensive subjects (53.7%) had grade I hypertension; blood pressure was controlled in 64.9%, and 54.8% showed left ventricular structural changes. Comparison between the normotensive and hypertensive groups showed no significant differences in parameters of global longitudinal or circumferential systolic strain. Application of the cut-offs to the hypertensive group identified 35 individuals (15.3%) as having subclinical left ventricular systolic dysfunction as assessed by global longitudinal myocardial strain parameters. CONCLUSIONS In this group of hypertensive patients, global myocardial strain parameters identified a group of individuals with subclinical left ventricular systolic dysfunction despite preserved ejection fraction. The clinical relevance of these findings needs to be assessed in long-term follow-up studies.

Anomalous insertion of the papillary muscle in a patient with sickle cell disease: A normal variant with no left ventricular outflow obstruction

© 2012 Sociedade Portuguesa de Cardiologia Published by Elsevier Espana, S.L. All rights reserved.

Strain balance of papillary muscles as a prerequisite for successful mitral valve repair in patients with mitral valve prolapse due to fibroelastic deficiency

AIMS The aim of this study was to assess the papillary muscle strain as a contributor to recurrent mitral regurgitation (MR) after mitral valve repair for fibroelastic deficiency. METHODS AND RESULTS Sixty-four patients with isolated posterior mitral valve prolapse and severe MR referred for surgery were prospectively recruited between 2008 and 2012. Two- and three-dimensional echocardiography and speckle tracking were performed in all patients. The longitudinal strain of the anterolateral (AL) and posteromedial (PM) papillary muscles was individually calculated as well as the global longitudinal strain of both papillary muscles was measured before and after mitral repair and normalized to left ventricle end-diastolic volume. Eight patients (12.5%) had at least moderate MR 6 months after mitral repair. The longitudinal strain of the AL (preop -4.94 ± 2.2 vs. postop -3.28 ± 1.3, P < 0.001) and the PM papillary muscles (preop -12.64 ± 5.3 vs. postop -4.12 ± 6.77, P < 0.001) as well as the global strain of both papillary muscles (preop -7.59 ± 3.48 vs. postop -1.07 ± 6, P < 0.001) were all reduced after surgical repair. The longitudinal strain of the PM papillary muscle was the strongest predictor of recurrent MR (when less than or equal to -14.78). The global preoperative papillary muscle strain was also a determinant of recurrent MR when the global strain was greater than -9.05% (area under the curve: 0.895, sensitivity: 100%, and specificity: 76.8%). CONCLUSIONS Patients with isolated posterior mitral leaflet prolapse are less likely having any residual MR post repair when the global papillary muscle strain of both papillary muscles is close or equal to zero. Strain of the papillary muscles may be an important determinant in predicting residual MR in patients who undergo mitral valve repair.