Ferande Peters

Prednisolone and Mycobacterium indicus pranii in Tuberculous Pericarditis

BACKGROUND Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Therapy of ischemic cardiomyopathy with the immunomodulating agent pentoxifylline: results of a randomized study.

Background—Inflammatory immune activation commonly occurs in heart failure and may perpetuate this syndrome. We sought to determine whether the immunomodulating agent pentoxifylline enhances left ventricular function in patients with ischemic cardiomyopathy. We also investigated the effect of therapy on levels of brain natriuretic peptide (NT-pro BNP), C-reactive protein (CRP), tumor necrosis factor-&agr; (TNF-&agr;), and the marker of apoptosis, Fas/Apo-1. Methods and Results—In a single-center, prospective, randomized, double-blind, placebo-controlled study, 38 patients with ischemic cardiomyopathy received pentoxifylline 400 mg TID or placebo in addition to standard therapy. Clinical assessment, radionuclide ventriculography, echocardiography, and blood analyses were performed at baseline and after 6 months. There were no differences in baseline characteristics between the groups. Five patients died (4 in the placebo group). Pentoxifylline treatment resulted in an improvement in functional class (P <0.005) and an increase in systolic blood pressure (P <0.05) and left ventricular radionuclide ejection fraction (P <0.05) compared with the placebo-treated group. There were reductions in plasma concentrations of CRP, NT-pro BNP, TNF-&agr;, and Fas/Apo-1 in the pentoxifylline compared with the placebo-treated group. Conclusions—In patients with heart failure due to ischemic left ventricular dysfunction, the addition of pentoxifylline to standard therapy results in improvements in clinical status and radionuclide ejection fraction, which are accompanied by reductions in plasma markers of inflammation, prognosis, and apoptosis.

Left ventricular twist in left ventricular noncompaction.

AIMS Left ventricular (LV) twist is an important component of systolic function. The effect of abnormal LV twist on adverse remodelling of the heart in left ventricular noncompaction (LVNC) is unknown. This study used speckle-tracking echocardiography to evaluate LV twist in patients with LVNC and determine whether abnormal LV twist is associated with more adverse LV remodelling. METHODS AND RESULTS Clinical, echocardiographic, and myocardial deformation characteristics were prospectively compared between 60 subjects diagnosed with LVNC and 59 age-matched healthy controls. Net instantaneous twist was defined as: peak apical rotation minus isochronous basal rotation. Normal rotation during systole was defined based on the 2010 ASE/EAE consensus document. Rigid body rotation (RBR) was determined present if the apex and base moved in the same direction during ejection. Rigid body rotation was found in 32 (53.3%) subjects with LVNC. The 28 subjects with LVNC and normal LV rotation had diminished apical rotation, basal rotation, and net twist compared with normal controls (P < 0.0001). Patients with LVNC and RBR had worse NYHA functional status (P < 0.0001), but similar echocardiographic indices of remodelling, ejection fraction, and strain parameters as those with LVNC and normal LV rotation. CONCLUSION Left ventricular twist is diminished in subjects with LVNC and normal LV rotation. Rigid body rotation occurs in 53.3% of subjects with LVNC and is not associated with more adverse remodelling than subjects with LVNC and normal LV rotation.

Rationale and design of the Investigation of the Management of Pericarditis (IMPI) trial: a 2 × 2 factorial randomized double-blind multicenter trial of adjunctive prednisolone and Mycobacterium w immunotherapy in tuberculous pericarditis.

BACKGROUND In spite of antituberculosis chemotherapy, tuberculous (TB) pericarditis causes death or disability in nearly half of those affected. Attenuation of the inflammatory response in TB pericarditis may improve outcome by reducing cardiac tamponade and pericardial constriction, but there is uncertainty as to whether adjunctive immunomodulation with corticosteroids and Mycobacterium w (M. w) can safely reduce mortality and morbidity. OBJECTIVES The primary objective of the IMPI Trial is to assess the effectiveness and safety of prednisolone and M. w immunotherapy in reducing the composite outcome of death, constriction, or cardiac tamponade requiring pericardial drainage in 1,400 patients with TB pericardial effusion. DESIGN The IMPI trial is a multicenter international randomized double-blind placebo-controlled 2 × 2 factorial study. Eligible patients are randomly assigned to receive oral prednisolone or placebo for 6 weeks and M. w injection or placebo for 3 months. Patients are followed up at weeks 2, 4, and 6 and months 3 and 6 during the intervention period and 6-monthly thereafter for up to 4 years. The primary outcome is the first occurrence of death, pericardial constriction, or cardiac tamponade requiring pericardiocentesis. The secondary outcome is safety of immunomodulatory treatment measured by effect on opportunistic infections (eg, herpes zoster) and malignancy (eg, Kaposi sarcoma) and impact on measures of immunosuppression and the incidence of immune reconstitution disease. CONCLUSIONS IMPI is the largest trial yet conducted comparing adjunctive immunotherapy in pericarditis. Its results will define the role of adjunctive corticosteroids and M. w immunotherapy in patients with TB pericardial effusion.

Left ventricular twist in a normal African adult population

AIMS Speckle tracking has emerged as a quantitative technique for assessing left ventricular (LV) function. However, no normative data for LV twist using speckle tracking echocardiography (STE) are available in the black population. This study assessed myocardial mechanics by determining LV twist parameters in different age groups using STE, and evaluated the effect of ageing on LV twist in this population. METHODS AND RESULTS The study population consisted of 127 healthy volunteers divided into four age groups: 20-29 (n = 34); 30-39 (n = 33); 40-49 (n = 29); and 50-65 (n = 31) years. Parasternal short-axis images of three consecutive end-expiratory cardiac cycles at LV basal, papillary muscle, and apical levels, and apical four-chamber images were obtained. Apical and (AR) basal (BR) LV peak systolic rotation during ejection and instantaneous LV peak systolic twist (net twist, defined as maximal value of instantaneous AR minus BR) were measured. Mean strain values were -17.28 ± 3.30% for longitudinal, -17.40 ± 3.29% for circumferential, and 57.49 ± 3.32% for radial strain. Mean rotational values were AR (5.56 ± 1.98°), BR (-3.31 ± 0.92°), and net twist (8.87 ± 2.21°). AR, BR, and net twist increased with age, whereas longitudinal, circumferential, and radial strain decreased with age. Multivariate linear regression analysis showed age as the main predictor of net twist (R(2) = 0.82, P < 0.0001). CONCLUSION These data establish values for strain and twist in a normal black adult population. Net twist increases with age, whereas strain parameters decrease. Age is the strongest independent predictor of LV twist.

Isolated Left Ventricular Noncompaction: What Do We Really Know?

Isolated left ventricular noncompaction (ILVNC) is a myocardial disorder thought to occur as a result of an arrest in embryogenesis. Recently, it has been classified as a genetic cardiomyopathy. Familial and sporadic forms of ILVNC have been documented. There is considerable genetic heterogeneity among familial forms, although sarcomeric mutations are the most common genetic mutations. Issues related to familial screening require careful consideration and future research. There is considerable controversy regarding several aspects relating to pathogenesis, diagnosis, and management of subjects with ILVNC. Differentiating some cases of ILVNC from normal variant myocardial architecture is challenging and requires future work. This review is intended to provide clinicians insight into several aspects of these challenging issues and offer some practical guidance in dealing with some of these difficult clinical scenarios.

Congenital submitral aneurysm with rupture into the left atrium: assessment by 2D and 3D transesophageal echocardiography.

We describe two cases of congenital submitral aneurysms (SMAs) in which three‐dimensional transesophageal echocardiography (3D TEE) proved useful to define the spatial extent of these aneurysms. In both cases, rupture into the left atrium was accurately delineated. 3D TEE was useful in case 1 as it depicted the precise site of rupture into the left atrium as well as pseudoprolapse of the P2 segment of the mitral valve. In case 2 it also localized the rupture into the left atrium in relation to the annulus to be adjacent to the anterolateral commissure. In addition, a cleft between the A1 and A2 scallops were identified and together with failure of the leaflets to coapt enabled the mechanisms contributing to the mitral regurgitation to be elucidated. Thus, imaging from the left atrial perspective using 3D TEE provided superior spatial anatomical delineation of the rupture and its relationship to the mitral valve, as well as accurate anatomical definition of the mitral leaflets. This information provides added benefit to the surgeon in planning a transatrial surgical repair of the SMAs. 3D TEE is superior to conventional 2D TEE in defining the spatial anatomy of SMAs as well as the mechanisms contributing to mitral regurgitation. (Echocardiography 2011;28:E121‐E124)

Isolated Left Ventricular Noncompaction in Identical Twins

The investigators describe 35-year-old monozygotic twins who presented 6 months apart with heart failure. In conclusion, this is the first report of adult monozygotic twins with isolated left ventricular noncompaction who presented with similar clinical and echocardiographic features and abnormal twist mechanics.

Isolated left ventricular non-compaction with normal ejection fraction : case report

Isolated left ventricular non-compaction (LVNC) is a genetic disease that is being increasingly recognised in patients presenting with heart failure of unknown origin. In this case report, we describe a patient with classic LVNC without clinical heart failure and with normal left ventricular ejection fraction.

Left atrial volume and strain parameters using echocardiography in a black population

Aims Left atrial (LA) volume is an important predictor of morbidity and mortality in cardiovascular disease. Left atrial strain is a feasible technique for assessing LA function. The EchoNoRMAL study recently highlighted the possibility that ethnic‐based differences may exist in LA size. There is a paucity of data regarding LA parameters in an African population. We sought to establish normative values for LA volumetric and strain parameters in a black population. Methods and results This cross‐sectional study comprised 120 individuals between 18 and 70 years of age. Left atrial volumes were measured by biplane Simpsons method, and strain parameters were measured using Philips QLAB 9 (Amsterdam, The Netherlands) speckle‐tracking software. The mean age was 38.7 ± 12.8 years (50% male). Maximum LA volume indexed (LAVi), pre‐atrial LAVi, and minimum LAVi were 19.7 ± 5.9, 12.2 ± 4.4, and 7.7 ± 3.2 mL/m2, respectively. Females had a higher LAVi compared with males (20.9 ± 6.3 vs. 18.6 ± 5.3 mL/m2, P = 0.04). Peak global longitudinal strain in the reservoir phase (&epsis;R) was 39.0 ± 8.3%, and the peak LA strain in the contractile phase (&epsis;CT) was −2.7 ± 2.5%. No gender differences were noted in &epsis;R. Body surface area, age, and weight were the main determinants of &epsis;R on multivariate linear regression analysis. Conclusion The data reported in this study establish the normal reference values for phasic LA volumes and strain in a normal black population and serve as a platform for future studies.