Fast breathhold cardiovascular magnetic resonance (CMR) has become a reference standard for the measurement of cardiac volumes, function, and mass. The implications of this for sample sizes for ...remodeling studies in heart failure (HF) have not been elucidated. We determined the reproducibility of CMR in HF and calculated the sample size requirements and compared them with published values for echocardiography. Breathhold gradient echo cines of the left ventricle were acquired in 20 patients with HF and 20 normal subjects. Sample size values were calculated from the interstudy standard deviation of the difference. The percentage variability of the measured parameters in our HF group of intraobserver (2.0-7.4%), interobserver (3.3-7.7%), and interstudy (2.5-4.8%) measurements was slightly larger than for our normal group (1.6-6.6%, 1.6-7.3%, and 2.0-7.3%, respectively) but remained comparable with previous studies in normal subjects. The calculated sample sizes in patients with HF for CMR to detect a 10-ml change in end-diastolic volume (n = 12) and end-systolic volume (n = 10), a 3% change in ejection fraction (n = 15), and a 10-g change in mass was (n = 9) were substantially smaller than recently published values for two-dimensional echocardiography (reduction of 81-97%). Breathhold CMR is a fast comprehensive technique for the assessment of cardiac volumes, function, and mass in HF that is accurate but also highly reproducible. This allows a considerable reduction in the patient numbers required to prove a hypothesis in research studies, which suggests a potential for important research cost savings.
Objectives We investigated the significance of fibrosis detected by late gadolinium enhancement cardiovascular magnetic resonance for the prediction of major clinical events in hypertrophic ...cardiomyopathy (HCM). Background The role of myocardial fibrosis in the prediction of sudden death and heart failure in HCM is unclear with a lack of prospective data. Methods We assessed the presence and amount of myocardial fibrosis in HCM patients and prospectively followed them for the development of morbidity and mortality in patients over 3.1 ± 1.7 years. Results Of 217 consecutive HCM patients, 136 (63%) showed fibrosis. Thirty-four of the 136 patients (25%) in the fibrosis group but only 6 of 81 (7.4%) patients without fibrosis reached the combined primary end point of cardiovascular death, unplanned cardiovascular admission, sustained ventricular tachycardia or ventricular fibrillation, or appropriate implantable cardioverter-defibrillator discharge (hazard ratio HR: 3.4, p = 0.006). In the fibrosis group, overall risk increased with the extent of fibrosis (HR: 1.18/5% increase, p = 0.008). The risk of unplanned heart failure admissions, deterioration to New York Heart Association functional class III or IV, or heart failure-related death was greater in the fibrosis group (HR: 2.5, p = 0.021), and this risk increased as the extent of fibrosis increased (HR: 1.16/5% increase, p = 0.017). All relationships remained significant after multivariate analysis. The extent of fibrosis and nonsustained ventricular tachycardia were univariate predictors for arrhythmic end points (sustained ventricular tachycardia or ventricular fibrillation, appropriate implantable cardioverter-defibrillator discharge, sudden cardiac death) (HR: 1.30, p = 0.014). Nonsustained ventricular tachycardia remained an independent predictor of arrhythmic end points after multivariate analysis, but the extent of fibrosis did not. Conclusions In patients with HCM, myocardial fibrosis as measured by late gadolinium enhancement cardiovascular magnetic resonance is an independent predictor of adverse outcome. (The Prognostic Significance of Fibrosis Detection in Cardiomyopathy; NCT00930735 )
Objectives: Takayasu’s arteritis (TA) is a rare disease, in which early diagnosis and assessment of treatment efficacy remain a problem. Signs and symptoms may be non-specific and conventional blood ...tests unreliable, with vascular inflammation often persisting in the face of a normal acute phase response. The current “gold standard” investigation, x ray angiography, is invasive and only identifies late, structural changes in vessels. Recently, non-invasive imaging methods have shown promise in the assessment of patients with TA. Methods: The invasive and non-invasive imaging performed on all patients in the rheumatology department at the Hammersmith Hospital between May 1996 and May 2002 who fulfilled the ACR criteria for TA were reviewed. All patients were clinically active at diagnosis and were treated with high dose oral prednisolone and additional oral or intravenous immunosuppression. Results: Non-invasive imaging methods (18Ffluorodeoxyglucose positron emission tomography (18FFDG-PET) and magnetic resonance imaging (MRI)) provided important additional information about disease activity (18FFDG-PET) and progression of vessel wall thickening (MRI) when compared with x ray angiography. Conclusions: Non-invasive imaging methods provide useful additional information towards the diagnosis and management of TA. Such techniques may allow earlier diagnosis and more accurate assessment of response to treatment than conventional clinical assessment and/or angiography. Non-invasive imaging is likely to be useful in the management of other large vessel vasculitides.
Increased extravascular compression and reduced diastolic perfusion time (DPT), rather than vascular remodeling, influence coronary microcirculatory dysfunction in aortic stenosis (AS). However, ...alterations after aortic valve replacement (AVR) remain unclear. The aim of the present study was to quantify changes in transmural perfusion and coronary vasodilator reserve (CVR), a measure of microcirculatory function, after AVR and determine the relative contribution of left ventricular mass (LVM) regression, change in aortic valve area (AVA), and DPT.
Twenty-two patients with AS were studied before and 1 year after AVR using echocardiography to measure AVA, cardiovascular magnetic resonance to assess LVM, and positron emission tomography to quantify resting and hyperemic myocardial blood flow (MBF) and CVR. Regression of LVM occurred in all patients (from 129+/-30 to 94+/-24 g/m2; P<0.0001), and there was a significant reduction in resting MBF and increase in CVR corrected for rate-pressure product after AVR, although these changes displayed marked heterogeneity. Regression of LVM was linearly related to change in resting total LV blood flow but not CVR. Increase in hyperemic MBF and CVR transmurally was directly related to the increase in AVA after AVR. A significant relationship existed between the change in hyperemic DPT (1.0+/-4.7 s/min range, 6.8 to 9.6) and change in transmural CVR (y=0.08x+0.18; r=0.44; P=0.04).
Changes in coronary microcirculatory function in patients with AS after AVR are not directly dependent on regression of LVM. Reduced extravascular compression and increased DPT are proposed as the main mechanisms for improvement in MBF and CVR after AVR.
The improvement in left-ventricular ejection fraction (LVEF) in response to β blockers is heterogeneous in patients with heart failure due to ischaemic heart disease, possibly indicating variations ...in the myocardial substrate underlying left-ventricular dysfunction. We investigated whether improvement in LVEF was associated with the volume of hibernating myocardium (viable myocardium with contractile failure).
We did a double-blind, randomised trial to compare placebo and carvedilol for 6 months in individuals with stable, chronic heart failure due to ischaemic left-ventricular systolic dysfunction. We enrolled 489 patients, of whom 387 were randomised. Patients were designated hibernators or non-hibernators according to the volume of hibernating myocardium. The primary endpoint was change in LVEF, measured by radionuclide ventriculography, in hibernators versus non-hibernators, on carvedilol compared with placebo. Analysis was by intention to treat.
82 patients dropped out of the study because of adverse events, withdrawal of consent, or failure to complete the investigation. Thus, 305 (79%) were analysed. LVEF was unchanged with placebo (mean change −0·4 SE 0·9 and −0·4 0·8 for non-hibernators and hibernators, respectively) but increased with carvedilol (2–5 0·9 and 3–2 0·8, respectively; p<0·0001 compared with baseline). Mean placebo-subtracted change in LVEF was 3·2% (95% CI 1–8–4–7; p=0·0001) overall, and 2·9% (0·7–5–1; p=0·011) and 3·6% (1–7–5–4; p=0·0002) in non-hibernators and hibernators, respectively. Effect of hibernator status on response of LVEF to carvedilol was not significant (0·7 −2·2 to 3–5; p=0·644). However, patients with more myocardium affected by hibernation or by hibernation and ischaemia had a greater increase in LVEF on carvedilol (p=0·0002 and p=0·009, respectively).
Some of the effect of carvedilol on LVEF might be mediated by improved function of hibernating or ischaemic myocardium, or both. Medical treatment might be an important adjunct or alternative to revascularisation for patients with hibernating myocardium.
Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM) patients. Treatment effects with improved left ventricular (LV) ejection ...fraction (EF) have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful.
This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR) to the relative risk (RR) of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM) and 63-70% (lower half of the normal range for TM).
A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p < 0.001) and the higher EF stratum (EF 63-70%, RR 0.893 p = 0.001).
These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.
Although earlier trauma exposure is known to predict posttraumatic stress disorder (PTSD) after subsequent traumas, it is unclear whether this association is limited to cases where the earlier trauma ...led to PTSD. Resolution of this uncertainty has important implications for research on pretrauma vulnerability to PTSD. We examined this issue in the World Health Organization (WHO) World Mental Health (WMH) Surveys with 34 676 respondents who reported lifetime trauma exposure. One lifetime trauma was selected randomly for each respondent. DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, 4th Edition) PTSD due to that trauma was assessed. We reported in a previous paper that four earlier traumas involving interpersonal violence significantly predicted PTSD after subsequent random traumas (odds ratio (OR)=1.3-2.5). We also assessed 14 lifetime DSM-IV mood, anxiety, disruptive behavior and substance disorders before random traumas. We show in the current report that only prior anxiety disorders significantly predicted PTSD in a multivariate model (OR=1.5-4.3) and that these disorders interacted significantly with three of the earlier traumas (witnessing atrocities, physical violence victimization and rape). History of witnessing atrocities significantly predicted PTSD after subsequent random traumas only among respondents with prior PTSD (OR=5.6). Histories of physical violence victimization (OR=1.5) and rape after age 17 years (OR=17.6) significantly predicted only among respondents with no history of prior anxiety disorders. Although only preliminary due to reliance on retrospective reports, these results suggest that history of anxiety disorders and history of a limited number of earlier traumas might usefully be targeted in future prospective studies as distinct foci of research on individual differences in vulnerability to PTSD after subsequent traumas.
Aims To compare an echocardiographic method for detecting abnormal cardiac function before development of overt cardiomyopathy with a recently validated technique of quantifying myocardial iron load. ...Methods and results We examined thalassaemia patients whose myocardial iron load had been evaluated with magnetic resonance imaging (MRI). By tissue Doppler echocardiography, myocardial velocities were sampled continuously from base to apex in the RV and LV free wall, and the septum in 52 patients aged 29.2 (14.2–43.1) years and 52 age-matched controls. Ninety-six percent of patients had normal LV ejection fraction by MRI. Thirty-eight (73%) had abnormal iron loading of the myocardium, and 33 of those had regional wall motion abnormalities detected in the septum (n=29), LV (n=2), RV (n=1), and septum plus LV (n=1). The incidence of wall motion abnormalities was significantly higher (P<0.04) in patients with myocardial iron overload (87%) than in the 14 without (35%). Furthermore, myocardial iron overload was suggested by a low T2*(15.1±15.8 ms) in patients with wall motion abnormalities vs those with normal wall motion (T2*: 30±19 ms) (P<0.007). Conclusions Wall motion abnormalities may represent an early sign of cardiac disease despite preserved global function. The regional abnormalities are related to iron overload and easily detectable with tissue Doppler echocardiography.
In vivo cardiac diffusion tensor imaging (cDTI) is uniquely capable of interrogating laminar myocardial dynamics non-invasively. A comprehensive dataset of quantative parameters and comparison with ...subject anthropometrics is required.
cDTI was performed at 3T with a diffusion weighted STEAM sequence. Data was acquired from the mid left ventricle in 43 subjects during the systolic and diastolic pauses. Global and regional values were determined for fractional anisotropy (FA), mean diffusivity (MD), helix angle gradient (HAg, degrees/%depth) and the secondary eigenvector angulation (E2A). Regression analysis was performed between global values and subject anthropometrics.
All cDTI parameters displayed regional heterogeneity. The RR interval had a significant, but clinically small effect on systolic values for FA, HAg and E2A. Male sex and increasing left ventricular end diastolic volume were associated with increased systolic HAg. Diastolic HAg and systolic E2A were both directly related to left ventricular mass and body surface area. There was an inverse relationship between E2A mobility and both age and ejection fraction.
Future interpretations of quantitative cDTI data should take into account anthropometric variations observed with patient age, body surface area and left ventricular measurements. Further work determining the impact of technical factors such as strain and SNR is required.
Abstract Background Cardiomyocytes are organized in microstructures termed sheetlets that reorientate during left ventricular thickening. Diffusion tensor cardiac magnetic resonance (DT-CMR) may ...enable noninvasive interrogation of in vivo cardiac microstructural dynamics. Dilated cardiomyopathy (DCM) is a condition of abnormal myocardium with unknown sheetlet function. Objectives This study sought to validate in vivo DT-CMR measures of cardiac microstructure against histology, characterize microstructural dynamics during left ventricular wall thickening, and apply the technique in hypertrophic cardiomyopathy (HCM) and DCM. Methods In vivo DT-CMR was acquired throughout the cardiac cycle in healthy swine, followed by in situ and ex vivo DT-CMR, then validated against histology. In vivo DT-CMR was performed in 19 control subjects, 19 DCM, and 13 HCM patients. Results In swine, a DT-CMR index of sheetlet reorientation (E2A) changed substantially (E2A mobility ∼46°). E2A changes correlated with wall thickness changes (in vivo r2 = 0.75; in situ r2 = 0.89), were consistently observed under all experimental conditions, and accorded closely with histological analyses in both relaxed and contracted states. The potential contribution of cyclical strain effects to in vivo E2A was ∼17%. In healthy human control subjects, E2A increased from diastole (18°) to systole (65°; p < 0.001; E2A mobility = 45°). HCM patients showed significantly greater E2A in diastole than control subjects did (48°; p < 0.001) with impaired E2A mobility (23°; p < 0.001). In DCM, E2A was similar to control subjects in diastole, but systolic values were markedly lower (40°; p < 0.001) with impaired E2A mobility (20°; p < 0.001). Conclusions Myocardial microstructure dynamics can be characterized by in vivo DT-CMR. Sheetlet function was abnormal in DCM with altered systolic conformation and reduced mobility, contrasting with HCM, which showed reduced mobility with altered diastolic conformation. These novel insights significantly improve understanding of contractile dysfunction at a level of noninvasive interrogation not previously available in humans.
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