Biomarkers to assess right heart pressures in recipients of a heart transplant: a proof-of-concept study

Background: This proof-of-concept study investigated the feasibility of using biomarkers to monitor right heart pressures (RHP) in heart transplanted (HTx) patients. Methods: In 298 patients, we measured 7.6 years post-HTx mean pressures in the right atrium (mRAP) and pulmonary artery (mPAP) and capillaries (mPCWP) along with plasma high-sensitivity troponin T (hsTnT), a marker of cardiomyocyte injury, and the multidimensional urinary classifiers HF1 and HF2, mainly consisting of dysregulated collagen fragments. Results: In multivariable models, mRAP and mPAP increased with hsTnT (per 1-SD, +0.91 and +1.26 mm Hg; P < 0.0001) and with HF2 (+0.42 and +0.62 mm Hg; P ≤ 0.035), but not with HF1. mPCWP increased with hsTnT (+1.16 mm Hg; P < 0.0001), but not with HF1 or HF2. The adjusted odds ratios for having elevated RHP (mRAP, mPAP or mPCWP ≥10, ≥24, ≥17 mm Hg, respectively) were 1.99 for hsTnT and 1.56 for HF2 (P ≤ 0.005). In detecting elevated RHPs, areas under the curve were similar for hsTnT and HF2 (0.63 vs 0.65; P = 0.66). Adding hsTnT continuous or per threshold or HF2 continuous to a basic model including all covariables did not increase diagnostic accuracy (P ≥ 0.11), whereas adding HF2 per optimized threshold increased both the integrated discrimination (+1.92%; P = 0.023) and net reclassification (+30.3%; P = 0.010) improvement. Conclusions: Correlating RHPs with noninvasive biomarkers in HTx patients is feasible. However, further refinement and validation of such biomarkers is required before their clinical application can be considered

Non-invasive assessment of atherosclerotic coronary lesion length using multidetector computed tomography angiography: comparison to quantitative coronary angiography

Multidetector computed tomography angiography (CTA) provides information on plaque extent and stenosis in the coronary wall. More accurate lesion assessment may be feasible with CTA as compared to invasive coronary angiography (ICA). Accordingly, lesion length assessment was compared between ICA and CTA in patients referred for CTA who underwent subsequent percutaneous coronary intervention (PCI). 89 patients clinically referred for CTA were subsequently referred for ICA and PCI. On CTA, lesion length was measured from the proximal to the distal shoulder of the plaque. Quantitative coronary angiography (QCA) was performed to analyze lesion length. Stent length was recorded for each lesion. In total, 119 lesions were retrospectively identified. Mean lesion length on CTA was 21.4 ± 8.4 mm and on QCA 12.6 ± 6.1 mm. Mean stent length deployed was 17.4 ± 5.3 mm. Lesion length on CTA was significantly longer than on QCA (difference 8.8 ± 6.7 mm, P < 0.001). Moreover, lesion length visualized on CTA was also significantly longer than mean stent length (CTA lesion length-stent length was 4.2 ± 8.7 mm, P < 0.001). Lesion length assessed by CTA is longer than that assessed by ICA. Possibly, CTA provides more accurate lesion length assessment than ICA and may facilitate improved guidance of percutaneous treatment of coronary lesions

Apical traction: A novel visual echocardiographic parameter to predict survival in patients with pulmonary hypertension

In some pulmonary hypertension (PH) patients, we noted a motion pattern where the right ventricular (RV) apex is pulled towards to left ventricle (LV) during systole, caused by traction from the LV ('apical traction', AT). Herein, we characterize patients with AT to investigate its prognostic significance

Predictors of Mitral Regurgitation Recurrence in Patients With Heart Failure Undergoing Mitral Valve Annuloplasty

Restrictive mitral annuloplasty is a surgical treatment option for patients with heart failure (HF) and functional mitral regurgitation (MR). However, recurrent MR has been reported at mid-term follow-up. The aim of the present study was to identify the echocardiographic predictors of recurrent MR in patients with HF undergoing mitral annuloplasty. During a mean follow-up of 2.6 +/- 1.6 years, 109 patients with HF (49% ischemic and 51% idiopathic dilated cardiomyopathy) who had undergone mitral valve repair were followed up (of 122 total patients). The severity of MR was quantified, and the following parameters were measured before intervention and at the mid-term follow-up examination: left ventricular (LV) and left atrial volumes and dimensions, LV sphericity index, mitral annular area, and mitral valve geometry parameters. At mid-term follow-up, 21 patients presented with significant MR (grade 2 to 4), and 88 patients had only MR grade 0 to 1. Both groups of patients had had a similar preoperative MR grade, mitral annular area, and LV volume and dimension. In contrast, patients with recurrent MR had had increased preoperative posterior and anterior leaflet angles, tenting height, tenting area, and LV sphericity index compared to the patients without recurrent MR. Of the different parameters of mitral and LV geometry, the distal mitral anterior leaflet angle (hazard ratio 1.48, 95% confidence interval 1.32 to 1.66, p <0.001) and posterior leaflet angle (hazard ratio 1.13, 95% confidence interval 1.07 to 1.19, p <0.001) were independent determinants of MR at mid-term follow-up. In conclusion, in patients with HF of ischemic or idiopathic etiology and functional MR, distal mitral leaflet tethering and posterior mitral leaflet tethering were associated with recurrent MR after restrictive mitral annuloplasty. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:395-401)Cardiolog

Predictors of Mitral Regurgitation Recurrence in Patients With Heart Failure Undergoing Mitral Valve Annuloplasty

Restrictive mitral annuloplasty is a surgical treatment option for patients with heart failure (HF) and functional mitral regurgitation (MR). However, recurrent MR has been reported at mid-term follow-up. The aim of the present study was to identify the echocardiographic predictors of recurrent MR in patients with HF undergoing mitral annuloplasty. During a mean follow-up of 2.6 +/- 1.6 years, 109 patients with HF (49% ischemic and 51% idiopathic dilated cardiomyopathy) who had undergone mitral valve repair were followed up (of 122 total patients). The severity of MR was quantified, and the following parameters were measured before intervention and at the mid-term follow-up examination: left ventricular (LV) and left atrial volumes and dimensions, LV sphericity index, mitral annular area, and mitral valve geometry parameters. At mid-term follow-up, 21 patients presented with significant MR (grade 2 to 4), and 88 patients had only MR grade 0 to 1. Both groups of patients had had a similar preoperative MR grade, mitral annular area, and LV volume and dimension. In contrast, patients with recurrent MR had had increased preoperative posterior and anterior leaflet angles, tenting height, tenting area, and LV sphericity index compared to the patients without recurrent MR. Of the different parameters of mitral and LV geometry, the distal mitral anterior leaflet angle (hazard ratio 1.48, 95% confidence interval 1.32 to 1.66, p <0.001) and posterior leaflet angle (hazard ratio 1.13, 95% confidence interval 1.07 to 1.19, p <0.001) were independent determinants of MR at mid-term follow-up. In conclusion, in patients with HF of ischemic or idiopathic etiology and functional MR, distal mitral leaflet tethering and posterior mitral leaflet tethering were associated with recurrent MR after restrictive mitral annuloplasty. (C) 2010 Elsevier Inc. All rights reserved. (Am J Cardiol 2010;106:395-401

Impairment of Angiogenesis-Driven Clot Resolution Is a Key Event in the Progression to Chronic Thromboembolic Pulmonary Hypertension: Validation in a Novel Rabbit Model

International audienceBACKGROUND: Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and rare complication of acute pulmonary embolism. Mechanisms underlying impaired clot resolution and in sustained fibrothrombotic obstruction of the pulmonary arterial bed remain poorly understood. Since defective angiogenesis correlated to defective clot resolution based on observations in surgical material from patients with CTEPH, we aimed to validate its crucial pathogenic role by intrathrombus inhibition of angiogenesis in a novel CTEPH rabbit model. METHODS: We aimed to compare whether intrathrombus administration of an antifibrinolytic agent, tranexamic acid, or an inhibitor of angiogenesis, SU5416, would contribute to CTEPH progression. Both products were administered on a weekly basis by autologous clot embolization in rabbits. Right ventricular pressure was monitored by telemetry, right ventricular function by transthoracic echocardiography, and a complete pulmonary hemodynamic evaluation was obtained through right heart catheterization. Markers of inflammation, endothelial dysfunction, heart failure, and fibrinolysis were measured in plasma. Pulmonary vessel remodeling was analyzed by immunohistochemistry. RESULTS: Impairing intrathrombus angiogenesis by repeatedly embolizing autologous blood clots containing SU5416 resulted in elevated mean pulmonary arterial pressure (38 mm Hg), increased indexed pulmonary vascular resistance, and enhanced right ventricular hypertrophy (80%, 1.9-fold, 36%, respectively, compared with rabbits embolized with clots containing an antifibrinolytic agent). This was caused by both obstruction of large pulmonary arteries with fibrothrombotic material and muscularization of pulmonary microvessels, and accompanied by inflammatory cell infiltration and increased circulating endothelin-1. CONCLUSIONS: The key role of angiogenesis-driven clot resolution was validated in a reliable small-animal model reproducing the major pathophysiological hallmarks of CTEPH