Denis Pellerin

Percutaneous Pulmonary Valve Implantation in Humans Results in 59 Consecutive Patients

Background—Right ventricular outflow tract (RVOT) reconstruction with valved conduits in infancy and childhood leads to reintervention for pulmonary regurgitation and stenosis in later life. Methods and Results—Patients with pulmonary regurgitation with or without stenosis after repair of congenital heart disease had percutaneous pulmonary valve implantation (PPVI). Mortality, hemodynamic improvement, freedom from explantation, and subjective and objective changes in exercise tolerance were end points. PPVI was performed successfully in 58 patients, 32 male, with a median age of 16 years and median weight of 56 kg. The majority had a variant of tetralogy of Fallot (n=36), or transposition of the great arteries, ventricular septal defect with pulmonary stenosis (n=8). The right ventricular (RV) pressure (64.4±17.2 to 50.4±14 mm Hg, P<0.001), RVOT gradient (33±24.6 to 19.5±15.3, P<0.001), and pulmonary regurgitation (PR) (grade 2 of greater before, none greater than grade 2 after, P<0.001) decreased significantly after PPVI. MRI showed significant reduction in PR fraction (21±13% versus 3±4%, P<0.001) and in RV end-diastolic volume (EDV) (94±28 versus 82±24 mL · beat−1 · m−2, P<0.001) and a significant increase in left ventricular EDV (64±12 versus 71±13 mL · beat−1 · m−2, P=0.005) and effective RV stroke volume (37±7 versus 42±9 mL · beat−1 · m−2, P=0.006) in 28 patients (age 19±8 years). A further 16 subjects, on metabolic exercise testing, showed significant improvement in &OV0312;o2max (26±7 versus 29±6 mL · kg−1 · min−1, P<0.001). There was no mortality. Conclusions—PPVI is feasible at low risk, with quantifiable improvement in MRI-defined ventricular parameters and pulmonary regurgitation, and results in subjective and objective improvement in exercise capacity.

Tissue Doppler, strain, and strain rate echocardiography for the assessment of left and right systolic ventricular function

Tissue Doppler (TDE), strain, and strain rate echocardiography are emerging real time ultrasound techniques that provide a measure of wall motion. They offer an objective means to quantify global and regional left and right ventricular function and to improve the accuracy and reproducibility of conventional echocardiography studies. Radial and longitudinal ventricular function can be assessed by the analysis of myocardial wall velocity and displacement indices, or by the analysis of wall deformation using the rate of deformation of a myocardial segment (strain rate) and its deformation over time (strain). A quick and easy assessment of left ventricular ejection fraction is obtained by mitral annular velocity measurement during a routine study, especially in patients with poor endocardial definition or abnormal septal motion. Strain rate and strain are less affected by passive myocardial motion and tend to be uniform throughout the left ventricle in normal subjects. This paper reviews the underlying principles of TDE, strain, and strain rate echocardiography and discusses currently available quantification tools and clinical applications.

Cohort Profile: Updating the cohort profile for the MRC National Survey of Health and Development: a new clinic-based data collection for ageing research

MRC Unit for Lifelong Health and Ageing, Research Department of Epidemiology and Public Health, University College London, London, UK, Clinical Radiology, Manchester Royal Infirmary, Oxford Road, Manchester, UK, Vascular Physiology Unit, Institute of Child Health, University College London, London, UK, MRC Epidemiology Unit, Cambridge, UK, Cardiovacular Institute, Sahlgrenska University Hospital, Göteborg, Sweden, Wellcome Trust Clinical Research Facility Manchester, Manchester, UK, International Centre for Circulatory Health, National Heart and Lung Institute, Imperial College London, London, UK, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK, Department of Echocardiography, The Heart Hospital, London, UK and MRC Human Nutrition Research, Cambridge, UK

Prevalence of exercise-induced left ventricular outflow tract obstruction in symptomatic patients with non-obstructive hypertrophic cardiomyopathy

Background: Resting left ventricular outflow tract obstruction (LVOTO) occurs in 25% of patients with hypertrophic cardiomyopathy (HCM) and is an important cause of symptoms and disease progression. The prevalence and clinical significance of exercise induced LVOTO in patients with symptomatic non-obstructive HCM is uncertain. Methods and results: 87 symptomatic patients (43.3 (13.7) years, 67.8% males) with HCM and no previously documented LVOTO (defined as a gradient ⩾30 mm Hg) underwent echocardiography during upright cardiopulmonary exercise testing: 54 patients (62.1%; 95% CI 51.5 to 71.6) developed LVOTO during exercise (latent LVOTO); 33 (37.9%; 95% CI 28.4 to 48.5) had neither resting nor exercise LVOTO (non-obstructive). Patients with latent LVOTO were more likely to have systolic anterior motion of the mitral valve (SAM) at rest (relative risk 2.1, 95% CI 1.2 to 3.8; p = 0.01), and higher peak oxygen consumption (mean difference: 10.3%, 95% CI 2.1 to 18.5; p = 0.02) than patients with non-obstructive HCM. The only independent predictors of Δ gradient during exercise were a history of presyncope/syncope, incomplete/complete SAM at rest and Wigle score (all p<0.05). Subsequent invasive reduction of LVOTO in 10 patients with latent obstruction and drug refractory symptoms resulted in improved functional class and less syncope/presyncope (all p<0.05). Conclusions: Approximately two-thirds of patients with symptomatic non-obstructive HCM have latent LVOTO. This study suggests that all patients with symptomatic non-obstructive HCM should have exercise stress echocardiography.

Diffuse myocardial fibrosis in severe aortic stenosis: an equilibrium contrast cardiovascular magnetic resonance study

AIMS Haemodynamics alone do not fully explain symptoms and prognosis in clinically severe aortic stenosis (AS). Myocardial disease, specifically diffuse myocardial fibrosis (DMF), may contribute. We used equilibrium contrast cardiovascular magnetic resonance (EQ-CMR) and sought to non-invasively measure DMF in severe AS and determine its clinical significance before and after valve replacement. METHODS AND RESULTS Patients with severe AS underwent echocardiography, brain natriuretic peptide (BNP), 6 min walk test (6MWT), and EQ-CMR pre- (n = 63) at baseline and at 6 months post- (n = 42) aortic valve replacement (AVR). EQ-CMR was also performed in 30 normal controls. Baseline: patients with AS had more DMF than controls (18 vs. 13%, P = 0.007) with a wide range (5-38%) that overlapped controls. The extent of diffuse fibrosis correlated inversely with the 6MWT performance (r(2) = 0.22, P = 0.001). Those with severe diastolic dysfunction had more DMF (P = 0.01). On multivariable analysis, the predictors of performance at 6MWT were diffuse fibrosis and BNP (P = 0.003 and 0.02, respectively). Post-op: following valve replacement, morphological and functional parameters improved [6 MWT, LA area, BNP, left ventricular (LV) hypertrophy, and volumes]. LV hypertrophy regression was shown to be cell volume reduction (P < 0.001) and not fibrosis regression (P = 0.54). Of the five deaths over six-month follow-up, four occurred in patients in the highest tertile of DMF. CONCLUSION DMF as measured by EQ-CMR is elevated in severe AS vs. normal controls but with a considerable overlap. It correlates with functional capacity at baseline. LV hypertrophy regression 6 months after AVR is cellular rather than fibrosis resolution.

Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T

Objectives: To identify in a prospective observational study the cardiac structural and functional abnormalities and mortality in patients with end stage renal disease (ESRD) with a raised cardiac troponin T (cTnT) concentration. Methods: 126 renal transplant candidates were studied over a two year period. Clinical, biochemical, echocardiographic, coronary angiographic, and dobutamine stress echocardiographic (DSE) data were examined in comparison with cTnT concentrations dichotomised at cut off concentrations of < 0.04 μg/l and < 0.10 μg/l. Results: Left ventricular (LV) size and filling pressure were significantly raised and LV systolic and diastolic function parameters significantly impaired in patients with raised cTnT, irrespective of the cut off concentration. The proportions of patients with diabetes and on dialysis were higher in both groups with raised cTnT. With a cut off cTnT concentration of 0.04 μg/l but not 0.10 μg/l, significantly more patients had severe coronary artery disease and a positive DSE result. The total ischaemic burden during DSE was similar in cTnT positive and negative patients, irrespective of the cut off concentration used. LV end systolic diameter index and E:Ea ratio were independent predictors of cTnT rises ⩾ 0.04 μg/l and ⩾ 0.10 μg/l, respectively. Diabetes was independently associated with cTnT at both cut off concentrations. Mortality was higher in all patients with raised cTnT. Conclusions: Patients with ESRD with raised cTnT concentrations have increased mortality. Raised concentrations are strongly associated with diabetes, LV dilatation, and impaired LV systolic and diastolic function, but not with severe coronary artery disease.

A randomized double-blind control study of early intra-coronary autologous bone marrow cell infusion in acute myocardial infarction: the REGENERATE-AMI clinical trial

Abstract Aims Clinical trials suggest that intracoronary delivery of autologous bone marrow-derived cells (BMCs) 1–7 days post-acute myocardial infarction (AMI) may improve left ventricular (LV) function. Earlier time points have not been evaluated. We sought to determine the effect of intracoronary autologous BMC on LV function when delivered within 24 h of successful reperfusion therapy. Methods and results A multi-centre phase II randomized, double-blind, and placebo-controlled trial. One hundred patients with anterior AMI and significant regional wall motion abnormality were randomized to receive either intracoronary infusion of BMC or placebo (1:1) within 24 h of successful primary percutaneous intervention (PPCI). The primary endpoint was the change in left ventricular ejection fraction (LVEF) between baseline and 1 year as determined by advanced cardiac imaging. At 1 year, although LVEF increased compared with baseline in both groups, the between-group difference favouring BMC was small (2.2%; 95% confidence interval, CI: −0.5 to 5.0; P = 0.10). However, there was a significantly greater myocardial salvage index in the BMC-treated group compared with placebo (0.1%; 95% CI: 0.0–0.20; P = 0.048). Major adverse events were rare in both treatment groups. Conclusion The early infusion of intracoronary BMC following PPCI for patients with AMI and regional wall motion abnormality leads to a small non-significant improvement in LVEF when compared with placebo; however, it may play an important role in infarct remodelling and myocardial salvage. Clinical trial registration Clinicaltrials.gov NCT00765453 and EudraCT 2007-002144-16.

Degenerative mitral valve disease with emphasis on mitral valve prolapse

Degenerative mitral valve disease is responsible for the syndromes of billowing mitral leaflet, mitral valve prolapse (MVP), floppy mitral valve, and flail leaflet.1–6 The pathology of these is mainly caused by myxomatous infiltration and fibroelastic deficiency. In the 1960s, Reid7 and Barlow and colleagues1 proposed that mid to late systolic clicks and apical late systolic murmurs were of mitral valvar origin. This origin was further documented by intracardiac phonocardiography.8 Criley and colleagues used “mitral valve prolapse” to describe posterior mitral leaflet motion in systole.9 Since then, MVP has remained a diagnosis of sustained interest and controversy. Because MVP is asymptomatic or has a non-specific clinical presentation, the disease is often detected by the non-ejection systolic click of the mitral valve and the late systolic murmur. MVP is clinically benign with potential for serious complications in otherwise healthy people, such as degenerative mitral regurgitation and infective endocarditis. Age and sex distributions as well as the frequencies of chest pain, dyspnoea, and ECG abnormalities were not significantly different between subjects with and without MVP,10–12 demonstrating that the previously reported associations were probably caused by a selection bias. These recent studies also showed that patients with MVP had lower body mass index than those without MVP. Many disorders have been associated with MVP but we do not know whether these associations are a casual coincidence, a common link or an expression of a genetic disturbance. Histologic patterns of degenerative mitral valve disease include myxomatous infiltration, fibroelastic deficiency, collagen alterations, and mucopolysaccharide accumulation.13 Elongated or ruptured chordae are often associated with these abnormalities. Because the distribution of mitral leaflet layers, namely auricularis, spongiosa, fibrosa, and ventricularis, is different in the basal, middle, and distal thirds of the leaflet, histologic abnormalities may vary accordingly. Myxomatous infiltration …

Raised plasma N-terminal pro-B-type natriuretic peptide concentrations predict mortality and cardiac disease in end-stage renal disease

N-terminal pro-B-type natriuretic peptide (NT-proBNP) concentrations are raised in a proportion of patients with heart failure and acute coronary syndrome and provide diagnostic and prognostic information. Inclusion cut-off values vary according to age, sex and estimated glomerular filtration rate (eGFR).1,2 Raised NT-proBNP concentrations are found in a proportion of patients with end-stage renal disease (ESRD). The significance and reasons for this remain uncertain. The objective of this study was to investigate whether NT-proBNP predicts mortality in a group of patients with ESRD. The secondary end point was to examine differences in patients with and without raised NT-proBNP, according to the cut-off value that best predicted mortality. One hundred and forty renal transplant candidates were prospectively studied. Long-term survival status was obtained in all patients. The study was approved by the local ethics committee. All participants gave written informed consent. All patients had baseline transthoracic echocardiography, dobutamine stress echocardiography (DSE) and coronary angiography. The protocol for these was previously described.3 A positive DSE response was described by the occurrence under stress of hypokinesia, akinesia or dyskinesia in one or more resting normal segments or worsening of wall motion in one or more resting hypokinetic segments. Significant coronary artery disease (CAD) was defined as luminal stenosis > 70% in one or more epicardial artery. Whole blood venous samples were collected at the time of DSE before infusion of dobutamine. Cardiac troponin T …

Midlife blood pressure change and left ventricular mass and remodelling in older age in the 1946 British birth cohort study

Aims Antecedent blood pressure (BP) may contribute to cardiovascular disease (CVD) independent of current BP. Blood pressure is associated with left ventricular mass index (LVMI) which independently predicts CVD. We investigated the relationship between midlife BP from age 36 to 64 and LVMI at 60–64 years. Methods and results A total of 1653 participants in the British 1946 Birth Cohort underwent BP measurement and echocardiography aged 60–64. Blood pressure had previously been measured at 36, 43, and 53 years. We investigated associations between BP at each age and rate of change in systolic blood pressure (SBP) between 36–43, 43–53, and 53–60/64 years on LVMI at 60–64 years. Blood pressure from 36 years was positively associated with LVMI. Association with SBP at 53 years was independent of SBP at 60–64 years and other potential confounders (fully adjusted β at 53 years = 0.19 g/m2; 95% CI: 0.11, 0.27; P < 0.001). Faster rates of increase in SBP from 43 to 53 years and 53 to 60/64 years were associated with increased LVMI. Similar relationships were seen for diastolic, pulse, and mean pressure. Rate of increase in SBP between 43–53 years was associated with largest change in LVMI (β at 43–53 years = 3.12 g/m2; 95% CI: 1.53, 4.72; P < 0.001). People on antihypertensive medication (43 years onwards) had greater LVMI even after adjustment for current BP (β at 43 years = 12.36 g/m2; 95% CI: 3.19, 21.53; P = 0.008). Conclusion Higher BP in midlife and rapid rise of SBP in 5th decade is associated with higher LVMI in later life, independent of current BP. People with treated hypertension have higher LVMI than untreated individuals, even accounting for their higher BP. Our findings emphasize importance of midlife BP as risk factor for future CVD.