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2.
Eur J Heart Fail ; 22(7): 1160-1170, 2020 07.
Article in English | MEDLINE | ID: mdl-32056322

ABSTRACT

AIMS: There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling. METHODS AND RESULTS: Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress). Regression analyses were used to evaluate predictors of change in LV ejection fraction (LVEF) over 12 months. We evaluated 56 participants (34 DCM patients, median LVEF 43%; 22 controls). Absolute LV contractile reserve predicted change in LVEF (1% increase associated with 0.4% increase in LVEF at 12 months, P = 0.02). Baseline myocardial strain (P = 0.39 global longitudinal strain), interstitial myocardial fibrosis (P = 0.41), replacement myocardial fibrosis (P = 0.25), and right ventricular contractile reserve (P = 0.17) were not associated with LV reverse remodelling. There was a poor correlation between contractile reserve and either LV extracellular volume fraction (r = -0.22, P = 0.23) or baseline LVEF (r = 0.07, P = 0.62). Men were more likely to experience adverse LV remodelling (P = 0.01) but age (P = 0.88) and disease-modifying heart failure medication (beta-blocker, P = 0.28; angiotensin-converting enzyme inhibitor, P = 0.92) did not predict follow-up LVEF. CONCLUSIONS: Substantial recovery of LV function occurs within 12 months in most patients with recent-onset DCM. Women had the greatest improvement in LVEF. A low LV contractile reserve measured by dobutamine stress CMR appears to identify patients whose LVEF is less likely to recover.


Subject(s)
Cardiomyopathy, Dilated , Heart Failure , Ventricular Dysfunction, Left , Cardiomyopathy, Dilated/diagnostic imaging , Contrast Media , Female , Gadolinium , Humans , Magnetic Resonance Spectroscopy , Male , Myocardial Contraction , Prospective Studies , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling
3.
Circulation ; 140(24): 1971-1980, 2019 12 10.
Article in English | MEDLINE | ID: mdl-31707827

ABSTRACT

BACKGROUND: Dobutamine stress echocardiography is widely used to test for ischemia in patients with stable coronary artery disease. In this analysis, we studied the ability of the prerandomization stress echocardiography score to predict the placebo-controlled efficacy of percutaneous coronary intervention (PCI) within the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina). METHODS: One hundred eighty-three patients underwent dobutamine stress echocardiography before randomization. The stress echocardiography score is broadly the number of segments abnormal at peak stress, with akinetic segments counting double and dyskinetic segments counting triple. The ability of prerandomization stress echocardiography to predict the placebo-controlled effect of PCI on response variables was tested by using regression modeling. RESULTS: At prerandomization, the stress echocardiography score was 1.56±1.77 in the PCI arm (n=98) and 1.61±1.73 in the placebo arm (n=85). There was a detectable interaction between prerandomization stress echocardiography score and the effect of PCI on angina frequency score with a larger placebo-controlled effect in patients with the highest stress echocardiography score (Pinteraction=0.031). With our sample size, we were unable to detect an interaction between stress echocardiography score and any other patient-reported response variables: freedom from angina (Pinteraction=0.116), physical limitation (Pinteraction=0.461), quality of life (Pinteraction=0.689), EuroQOL 5 quality-of-life score (Pinteraction=0.789), or between stress echocardiography score and physician-assessed Canadian Cardiovascular Society angina class (Pinteraction=0.693), and treadmill exercise time (Pinteraction=0.426). CONCLUSIONS: The degree of ischemia assessed by dobutamine stress echocardiography predicts the placebo-controlled efficacy of PCI on patient-reported angina frequency. The greater the downstream stress echocardiography abnormality caused by a stenosis, the greater the reduction in symptoms from PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02062593.


Subject(s)
Coronary Artery Disease/drug therapy , Dobutamine/pharmacology , Echocardiography, Stress/drug effects , Ischemia/drug therapy , Aged , Angina, Stable/diagnosis , Angina, Stable/drug therapy , Coronary Artery Disease/diagnosis , Dobutamine/administration & dosage , Exercise Tolerance/drug effects , Female , Humans , Ischemia/etiology , Ischemia/physiopathology , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Quality of Life
4.
JACC Cardiovasc Imaging ; 12(8 Pt 2): 1699-1708, 2019 08.
Article in English | MEDLINE | ID: mdl-30660522

ABSTRACT

OBJECTIVES: This study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling. BACKGROUND: Although regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear. METHODS: A total of 65 patients and 35 healthy control subjects underwent adenosine (140 µg/kg/min) stress perfusion cardiovascular magnetic resonance with late gadolinium enhancement imaging. Stress and rest MBF and MPR were derived using a modified Fermi-constrained deconvolution algorithm. RESULTS: Patients had significantly higher global rest MBF compared with control subjects (1.73 ± 0.42 ml/g/min vs. 1.14 ± 0.42 ml/g/min; p < 0.001). In contrast, global stress MBF was significantly lower versus control subjects (3.07 ± 1.02 ml/g/min vs. 3.53 ± 0.79 ml/g/min; p = 0.02), resulting in impaired MPR in the DCM group (1.83 ± 0.58 vs. 3.50 ± 1.45; p < 0.001). Global stress MBF (2.70 ± 0.89 ml/g/min vs. 3.44 ± 1.03 ml/g/min; p = 0.017) and global MPR (1.67 ± 0.61 vs. 1.99 ± 0.50; p = 0.047) were significantly reduced in patients with DCM with LV ejection fraction ≤35% compared with those with LV ejection fraction >35%. Segments with fibrosis had lower rest MBF (mean difference: -0.12 ml/g/min; 95% confidence interval: -0.23 to -0.01 ml/g/min; p = 0.035) and lower stress MBF (mean difference: -0.15 ml/g/min; 95% confidence interval: -0.28 to -0.03 ml/g/min; p = 0.013). CONCLUSIONS: Patients with DCM exhibit microvascular dysfunction, the severity of which is associated with the degree of LV impairment. However, rest MBF is elevated rather than reduced in DCM. If microvascular dysfunction contributes to the pathogenesis of DCM, then the underlying mechanism is more likely to involve stress-induced repetitive stunning rather than chronic myocardial hypoperfusion.


Subject(s)
Cardiomyopathy, Dilated/diagnostic imaging , Coronary Circulation , Magnetic Resonance Imaging, Cine , Microcirculation , Myocardial Perfusion Imaging/methods , Vasodilator Agents/administration & dosage , Ventricular Dysfunction, Left/diagnostic imaging , Ventricular Function, Left , Ventricular Remodeling , Adult , Cardiomyopathy, Dilated/pathology , Cardiomyopathy, Dilated/physiopathology , Case-Control Studies , Contrast Media/administration & dosage , Female , Fibrosis , Humans , Male , Middle Aged , Myocardium/pathology , Organometallic Compounds/administration & dosage , Predictive Value of Tests , Prognosis , Prospective Studies , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathology
5.
Circ Cardiovasc Imaging ; 11(9): e007722, 2018 09.
Article in English | MEDLINE | ID: mdl-30354674

ABSTRACT

BACKGROUND: Myocardial fibrosis, identified by late gadolinium enhancement cardiovascular magnetic resonance, predicts outcomes in chronic heart failure (HF). Its prognostic significance in new-onset HF and reduced left ventricular ejection fraction (LVEF) is unclear. We investigated whether the pattern and extent of fibrosis predict survival in new-onset HF and reduced LVEF of initially uncertain pathogenesis. METHODS AND RESULTS: Of 120 consecutive patients with new-onset (<6 months) HF and reduced LVEF, 31 (26%) had infarct fibrosis, 25 (21%) had midwall fibrosis, and 64 (53%) had no fibrosis. During median follow-up of 8.9 years, 33 (28%) patients died. Patients with infarct fibrosis (hazard ratios [HR], 3.32; 95% CI, 1.46-7.58; P=0.004) or midwall fibrosis (HR, 2.99; 95% CI, 1.24-7.19; P=0.014) were more likely to die compared with those without fibrosis. On multivariable analysis, the pattern and extent of fibrosis were both associated with all-cause mortality (by fibrosis pattern: infarct: HR, 2.60; 95% CI, 1.08-6.27; P=0.033; midwall: HR, 2.64; 95% CI, 1.08-6.47; P=0.034; by fibrosis extent per 1%: HR, 1.07; 95% CI, 1.03-1.12; P<0.001). Fibrosis pattern also predicted composites of cardiovascular mortality or aborted sudden cardiac death (infarct: HR, 3.45; 95% CI, 1.20-9.90; P=0.022; midwall: HR, 6.59; 95% CI, 2.26-19.22; P<0.001), and all-cause mortality, HF hospitalization, or aborted sudden cardiac death (infarct: HR, 2.69; 95% CI, 1.26-5.76; P=0.011; midwall fibrosis: HR, 2.97; 95% CI, 1.37-6.45; P=0.006). Addition of fibrosis pattern to LVEF improved risk prediction for all-cause mortality (LVEF versus LVEF+fibrosis C statistic: 0.66 versus 0.71; P=0.033). Importantly, the absence of fibrosis heralded a favorable prognosis with an 85% survival rate over the duration of follow-up. CONCLUSIONS: The pattern and extent of myocardial fibrosis predict adverse outcomes in new-onset HF and reduced LVEF. In contrast, the absence of fibrosis portends a durable warranty period with a low incidence of adverse events. These findings support a role for late gadolinium enhancement cardiovascular magnetic resonance in the early risk stratification of patients with HF of uncertain pathogenesis.


Subject(s)
Heart Failure/diagnostic imaging , Magnetic Resonance Imaging, Cine , Myocardium/pathology , Stroke Volume , Ventricular Function, Left , Ventricular Remodeling , Adult , Aged , Cause of Death , Female , Fibrosis , Heart Failure/pathology , Heart Failure/physiopathology , Heart Failure/therapy , Humans , Male , Middle Aged , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Risk Factors , Time Factors
6.
Circulation ; 138(17): 1780-1792, 2018 10 23.
Article in English | MEDLINE | ID: mdl-29789302

ABSTRACT

BACKGROUND: There are no data on how fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) are associated with the placebo-controlled efficacy of percutaneous coronary intervention (PCI) in stable single-vessel coronary artery disease. METHODS: We report the association between prerandomization invasive physiology within ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina), a placebo-controlled trial of patients who have stable angina with angiographically severe single-vessel coronary disease clinically eligible for PCI. Patients underwent prerandomization research FFR and iFR assessment. The operator was blinded to these values. Assessment of response variables, treadmill exercise time, stress echocardiography score, symptom frequency, and angina severity were performed at prerandomization and blinded follow-up. Effects were calculated by analysis of covariance. The ability of FFR and iFR to predict placebo-controlled changes in response variables was tested by using regression modeling. RESULTS: Invasive physiology data were available in 196 patients (103 PCI and 93 placebo). At prerandomization, the majority had Canadian Cardiovascular Society class II or III symptoms (150/196, 76.5%). Mean FFR and iFR were 0.69±0.16 and 0.76±0.22, respectively; 97% had ≥1 positive ischemia tests. The estimated effect of PCI on between-arm prerandomization-adjusted total exercise time was 20.7 s (95% confidence interval [CI], -4.0 to 45.5; P=0.100) with no interaction of FFR ( Pinteraction=0.318) or iFR ( Pinteraction=0.523). PCI improved stress echocardiography score more than placebo (1.07 segment units; 95% CI, 0.70-1.44; P<0.00001). The placebo-controlled effect of PCI on stress echocardiography score increased progressively with decreasing FFR ( Pinteraction<0.00001) and decreasing iFR ( Pinteraction<0.00001). PCI did not improve angina frequency score significantly more than placebo (odds ratio, 1.64; 95% CI, 0.96-2.80; P=0.072) with no detectable evidence of interaction with FFR ( Pinteraction=0.849) or iFR ( Pinteraction=0.783). However, PCI resulted in more patient-reported freedom from angina than placebo (49.5% versus 31.5%; odds ratio, 2.47; 95% CI, 1.30-4.72; P=0.006) but neither FFR ( Pinteraction=0.693) nor iFR ( Pinteraction=0.761) modified this effect. CONCLUSIONS: In patients with stable angina and severe single-vessel disease, the blinded effect of PCI was more clearly seen by stress echocardiography score and freedom from angina than change in treadmill exercise time. Moreover, the lower the FFR or iFR, the greater the magnitude of stress echocardiographic improvement caused by PCI. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02062593.


Subject(s)
Angina, Stable/therapy , Cardiac Catheterization , Coronary Artery Disease/therapy , Coronary Stenosis/therapy , Fractional Flow Reserve, Myocardial , Percutaneous Coronary Intervention , Adrenergic beta-1 Receptor Agonists/administration & dosage , Aged , Angina, Stable/diagnosis , Angina, Stable/physiopathology , Coronary Angiography , Coronary Artery Disease/diagnosis , Coronary Artery Disease/physiopathology , Coronary Stenosis/diagnosis , Coronary Stenosis/physiopathology , Dobutamine/administration & dosage , Echocardiography, Stress/methods , Exercise Test , Exercise Tolerance , Female , Health Status , Humans , Male , Middle Aged , Percutaneous Coronary Intervention/adverse effects , Predictive Value of Tests , Progression-Free Survival , Quality of Life , Recovery of Function , Severity of Illness Index , Time Factors , United Kingdom
7.
Lancet ; 391(10115): 31-40, 2018 01 06.
Article in English | MEDLINE | ID: mdl-29103656

ABSTRACT

BACKGROUND: Symptomatic relief is the primary goal of percutaneous coronary intervention (PCI) in stable angina and is commonly observed clinically. However, there is no evidence from blinded, placebo-controlled randomised trials to show its efficacy. METHODS: ORBITA is a blinded, multicentre randomised trial of PCI versus a placebo procedure for angina relief that was done at five study sites in the UK. We enrolled patients with severe (≥70%) single-vessel stenoses. After enrolment, patients received 6 weeks of medication optimisation. Patients then had pre-randomisation assessments with cardiopulmonary exercise testing, symptom questionnaires, and dobutamine stress echocardiography. Patients were randomised 1:1 to undergo PCI or a placebo procedure by use of an automated online randomisation tool. After 6 weeks of follow-up, the assessments done before randomisation were repeated at the final assessment. The primary endpoint was difference in exercise time increment between groups. All analyses were based on the intention-to-treat principle and the study population contained all participants who underwent randomisation. This study is registered with ClinicalTrials.gov, number NCT02062593. FINDINGS: ORBITA enrolled 230 patients with ischaemic symptoms. After the medication optimisation phase and between Jan 6, 2014, and Aug 11, 2017, 200 patients underwent randomisation, with 105 patients assigned PCI and 95 assigned the placebo procedure. Lesions had mean area stenosis of 84·4% (SD 10·2), fractional flow reserve of 0·69 (0·16), and instantaneous wave-free ratio of 0·76 (0·22). There was no significant difference in the primary endpoint of exercise time increment between groups (PCI minus placebo 16·6 s, 95% CI -8·9 to 42·0, p=0·200). There were no deaths. Serious adverse events included four pressure-wire related complications in the placebo group, which required PCI, and five major bleeding events, including two in the PCI group and three in the placebo group. INTERPRETATION: In patients with medically treated angina and severe coronary stenosis, PCI did not increase exercise time by more than the effect of a placebo procedure. The efficacy of invasive procedures can be assessed with a placebo control, as is standard for pharmacotherapy. FUNDING: NIHR Imperial Biomedical Research Centre, Foundation for Circulatory Health, Imperial College Healthcare Charity, Philips Volcano, NIHR Barts Biomedical Research Centre.


Subject(s)
Angina, Stable/surgery , Coronary Stenosis/surgery , Percutaneous Coronary Intervention , Aged , Angina, Stable/complications , Angina, Stable/diagnostic imaging , Coronary Angiography , Coronary Stenosis/complications , Coronary Stenosis/diagnostic imaging , Double-Blind Method , Exercise Tolerance , Female , Humans , Male , Middle Aged , Treatment Outcome , United Kingdom
8.
Circulation ; 128(15): 1623-33, 2013 Oct 08.
Article in English | MEDLINE | ID: mdl-23965488

ABSTRACT

BACKGROUND: Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM. METHODS AND RESULTS: We prospectively studied 250 consecutive DCM patients with the use of cardiovascular magnetic resonance. RVSD, defined by RV ejection fraction≤45%, was present in 86 (34%) patients. During a median follow-up period of 6.8 years, there were 52 deaths, and 7 patients underwent cardiac transplantation. The primary end point of all-cause mortality or cardiac transplantation was reached by 42 of 86 patients with RVSD and 17 of 164 patients without RVSD (49% versus 10%; hazard ratio, 5.90; 95% confidence interval [CI], 3.35-10.37; P<0.001). On multivariable analysis, RVSD remained a significant independent predictor of the primary end point (hazard ratio, 3.90; 95% CI, 2.16-7.04; P<0.001), as well as secondary outcomes of cardiovascular mortality or cardiac transplantation (hazard ratio, 3.35; 95% CI, 1.76-6.39; P<0.001), and heart failure death, heart failure hospitalization, or cardiac transplantation (hazard ratio, 2.70; 95% CI, 1.32-5.51; P=0.006). Assessment of RVSD improved risk stratification for all-cause mortality or cardiac transplantation (net reclassification improvement, 0.31; 95% CI 0.10-0.53; P=0.001). CONCLUSIONS: RVSD is a powerful, independent predictor of transplant-free survival and adverse heart failure outcomes in DCM. Cardiovascular magnetic resonance assessment of RV function is important in the evaluation and risk stratification of DCM patients.


Subject(s)
Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/pathology , Ventricular Dysfunction, Right/mortality , Ventricular Dysfunction, Right/pathology , Adult , Aged , Cardiomyopathy, Dilated/physiopathology , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Magnetic Resonance Imaging , Male , Middle Aged , Predictive Value of Tests , Prevalence , Prognosis , Prospective Studies , Risk Factors , Stroke Volume/physiology , Ventricular Dysfunction, Right/physiopathology , Ventricular Function, Right/physiology
9.
JAMA ; 309(9): 896-908, 2013 Mar 06.
Article in English | MEDLINE | ID: mdl-23462786

ABSTRACT

IMPORTANCE: Risk stratification of patients with nonischemic dilated cardiomyopathy is primarily based on left ventricular ejection fraction (LVEF). Superior prognostic factors may improve patient selection for implantable cardioverter-defibrillators (ICDs) and other management decisions. OBJECTIVE: To determine whether myocardial fibrosis (detected by late gadolinium enhancement cardiovascular magnetic resonance [LGE-CMR] imaging) is an independent and incremental predictor of mortality and sudden cardiac death (SCD) in dilated cardiomyopathy. DESIGN, SETTING, AND PATIENTS: Prospective, longitudinal study of 472 patients with dilated cardiomyopathy referred to a UK center for CMR imaging between November 2000 and December 2008 after presence and extent of midwall replacement fibrosis were determined. Patients were followed up through December 2011. MAIN OUTCOME MEASURES: Primary end point was all-cause mortality. Secondary end points included cardiovascular mortality or cardiac transplantation; an arrhythmic composite of SCD or aborted SCD (appropriate ICD shock, nonfatal ventricular fibrillation, or sustained ventricular tachycardia); and a composite of HF death, HF hospitalization, or cardiac transplantation. RESULTS: Among the 142 patients with midwall fibrosis, there were 38 deaths (26.8%) vs 35 deaths (10.6%) among the 330 patients without fibrosis (hazard ratio [HR], 2.96 [95% CI, 1.87-4.69]; absolute risk difference, 16.2% [95% CI, 8.2%-24.2%]; P < .001) during a median follow-up of 5.3 years (2557 patient-years of follow-up). The arrhythmic composite was reached by 42 patients with fibrosis (29.6%) and 23 patients without fibrosis (7.0%) (HR, 5.24 [95% CI, 3.15-8.72]; absolute risk difference, 22.6% [95% CI, 14.6%-30.6%]; P < .001). After adjustment for LVEF and other conventional prognostic factors, both the presence of fibrosis (HR, 2.43 [95% CI, 1.50-3.92]; P < .001) and the extent (HR, 1.11 [95% CI, 1.06-1.16]; P < .001) were independently and incrementally associated with all-cause mortality. Fibrosis was also independently associated with cardiovascular mortality or cardiac transplantation (by fibrosis presence: HR, 3.22 [95% CI, 1.95-5.31], P < .001; and by fibrosis extent: HR, 1.15 [95% CI, 1.10-1.20], P < .001), SCD or aborted SCD (by fibrosis presence: HR, 4.61 [95% CI, 2.75-7.74], P < .001; and by fibrosis extent: HR, 1.10 [95% CI, 1.05-1.16], P < .001), and the HF composite (by fibrosis presence: HR, 1.62 [95% CI, 1.00-2.61], P = .049; and by fibrosis extent: HR, 1.08 [95% CI, 1.04-1.13], P < .001). Addition of fibrosis to LVEF significantly improved risk reclassification for all-cause mortality and the SCD composite (net reclassification improvement: 0.26 [95% CI, 0.11-0.41]; P = .001 and 0.29 [95% CI, 0.11-0.48]; P = .002, respectively). CONCLUSIONS AND RELEVANCE: Assessment of midwall fibrosis with LGE-CMR imaging provided independent prognostic information beyond LVEF in patients with nonischemic dilated cardiomyopathy. The role of LGE-CMR in the risk stratification of dilated cardiomyopathy requires further investigation.


Subject(s)
Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/pathology , Death, Sudden, Cardiac/epidemiology , Myocardium/pathology , Ventricular Function, Left , Adult , Aged , Cause of Death , Defibrillators, Implantable , Female , Fibrosis , Gadolinium , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Patient Selection , Predictive Value of Tests , Prognosis , Prospective Studies , Risk Assessment , Stroke Volume , United Kingdom/epidemiology
10.
Eur J Heart Fail ; 15(6): 660-70, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23475781

ABSTRACT

AIMS: Echocardiographic studies have shown that left atrial volume (LAV) predicts adverse outcome in small heart failure (HF) cohorts of mixed aetiology. However, the prognostic value of LAV in non-ischaemic dilated cardiomyopathy (DCM) is unknown. Cardiovascular magnetic resonance (CMR) allows accurate and reproducible measurement of LAV. We sought to determine the long-term prognostic significance of LAV assessed by CMR in DCM. METHODS AND RESULTS: We measured LAV indexed to body surface area (LAVi) in 483 consecutive DCM patients referred for CMR. Patients were prospectively followed up for a primary endpoint of all-cause mortality or cardiac transplantation. During a median follow-up of 5.3 years, 75 patients died and 9 underwent cardiac transplantation. After adjustment for established risk factors, LAVi was an independent predictor of the primary endpoint [hazard ratio (HR) per 10 mL/m(2) 1.08; 95% confidence interval (CI) 1.01-1.15; P = 0.022]. LAVi was also independently associated with the secondary composite endpoints of cardiovascular mortality or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.19; P = 0.003), and HF death, HF hospitalization, or cardiac transplantation (HR per 10 mL/m(2) 1.11; 95% CI 1.04-1.18; P = 0.001). The optimal LAVi cut-off value for predicting the primary endpoint was 72 mL/m(2). Patients with LAVi >72 mL/m(2) had a three-fold elevated risk of death or transplantation (HR 3.00; 95% CI 1.92-4.70; P < 0.001). LAVi provided incremental prognostic value for the prediction of transplant-free survival (net reclassification improvement 0.17; 95% CI 0.05-0.29; P = 0.002). CONCLUSIONS: LAVi is a powerful independent predictor of transplant-free survival and HF outcomes in DCM. Assessment of LAV improves risk stratification in DCM and should be incorporated into routine CMR examination.


Subject(s)
Cardiac Volume/physiology , Cardiomyopathy, Dilated/physiopathology , Heart Atria/physiopathology , Magnetic Resonance Imaging, Cine , Adult , Aged , Cardiomyopathy, Dilated/mortality , Cardiomyopathy, Dilated/surgery , Cohort Studies , Female , Follow-Up Studies , Heart Transplantation , Humans , Male , Middle Aged , Observer Variation , Prognosis , Prospective Studies , Risk Factors
12.
Circulation ; 124(12): 1351-60, 2011 Sep 20.
Article in English | MEDLINE | ID: mdl-21900085

ABSTRACT

BACKGROUND: In patients presenting with new-onset heart failure of uncertain etiology, the role of coronary angiography (CA) is unclear. Although conventionally performed to differentiate underlying coronary artery disease from dilated cardiomyopathy, CA is associated with a risk of complications and may not detect an ischemic cause resulting from arterial recanalization or an embolic episode. In this study, we assessed the diagnostic accuracy of a cardiovascular magnetic resonance (CMR) protocol incorporating late gadolinium enhancement (LGE) and magnetic resonance CA as a noninvasive gatekeeper to CA in determining the etiology of heart failure in this subset of patients. METHODS AND RESULTS: One hundred twenty consecutive patients underwent CMR and CA. The etiology was ascribed by a consensus panel that used the results of the CMR scans. Similarly, a separate consensus group ascribed an underlying cause by using the results of CA. The diagnostic accuracy of both strategies was compared against a gold-standard panel that made a definitive judgment by reviewing all clinical data. The study was powered to show noninferiority between the 2 techniques. The sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 97% for LGE-CMR were equivalent to CA (sensitivity, 93%; specificity, 96%; and diagnostic accuracy, 95%). As a gatekeeper to CA, LGE-CMR was also found to be a cheaper diagnostic strategy in a decision tree model when United Kingdom-based costs were assumed. The economic merits of this model would change, depending on the relative costs of LGE-CMR and CA in any specific healthcare system. CONCLUSION: This study showed that LGE-CMR is a safe, clinically effective, and potentially economical gatekeeper to CA in patients presenting with heart failure of uncertain etiology.


Subject(s)
Cardiac Imaging Techniques/standards , Coronary Angiography , Heart Failure/diagnosis , Heart Failure/etiology , Magnetic Resonance Imaging/standards , Aged , Cardiac Imaging Techniques/economics , Cardiac Imaging Techniques/statistics & numerical data , Coronary Angiography/economics , Decision Trees , Female , Follow-Up Studies , Gadolinium , Health Care Costs , Heart Failure/economics , Humans , Magnetic Resonance Imaging/economics , Magnetic Resonance Imaging/statistics & numerical data , Male , Middle Aged , Observer Variation , Referral and Consultation/economics , Referral and Consultation/standards , Referral and Consultation/statistics & numerical data , Reproducibility of Results , Sensitivity and Specificity , United Kingdom
14.
J Magn Reson Imaging ; 31(1): 117-24, 2010 Jan.
Article in English | MEDLINE | ID: mdl-20027579

ABSTRACT

PURPOSE: To calculate the sample size for a theoretical pulmonary arterial hypertension (PAH) randomized controlled trial (RCT) by using cardiovascular magnetic resonance (CMR) imaging to determine the repeatability of measures between two scans. MATERIALS AND METHODS: Two same-day examinations from 10 PAH patients were analyzed manually and semiautomatically. Study size was calculated from the standard deviation (SD) of repeatability. Different approaches to right-ventricle (RV) mass were investigated, agreement between methods tested and interobserver reproducibility measured by Bland-Altman analysis to explore how the PAH heart might be best measured. RESULTS: Repeatability was good for almost all manually-measured indices but poor for semiautomated measurement of RV mass and left-ventricle (LV) end-diastolic volume (EDV). Thus, for an RCT (power, 80%; significance level, 5%) analyzing "outcome" indices (RVEDV, LVEDV, RV ejection fraction, and RV mass; anticipated change: 10 mL, 10 mL, 3%, and 10 g, respectively) manually, 34 patients are required compared to 78 if analysis is semiautomated. RV mass was repeatable if the interventricular septum was divided between ventricles or if wholly apportioned to the LV. Limits of agreement between manual and semiautomated analyses were unsatisfactory for RV measures and interobserver reproducibility was worse for semiautomated than manual analysis. CONCLUSION: Manual is more robust than semiautomated analysis and at present should be favored in RCTs in PAH as it leads to lower sample size requirements.


Subject(s)
Algorithms , Heart Ventricles/pathology , Hypertension, Pulmonary/diagnosis , Image Interpretation, Computer-Assisted/methods , Information Storage and Retrieval/methods , Magnetic Resonance Imaging/methods , Adult , Female , Humans , Image Enhancement/methods , Male , Randomized Controlled Trials as Topic/methods , Reproducibility of Results , Sample Size , Sensitivity and Specificity
15.
Arthritis Rheum ; 60(11): 3501-9, 2009 Nov.
Article in English | MEDLINE | ID: mdl-19877040

ABSTRACT

OBJECTIVE: This study was undertaken to evaluate the value of cardiovascular magnetic resonance (CMR) in the assessment of patients with Takayasu arteritis (TA). METHODS: Sixteen patients with TA and 2 populations comprising 110 normal volunteers were prospectively recruited. All patients with TA underwent a CMR protocol including measurement of carotid artery wall volume, assessment of left ventricular (LV) volumes and function, and late gadolinium enhancement for the detection of myocardial scarring. RESULTS: Carotid artery wall volume, total vessel volume, and the wall:outer wall ratio were elevated in TA patients compared with controls (wall volume 1,045 mm(3) in TA patients versus 640 mm(3) in controls, P < 0.001; total vessel volume 2,268 mm(3) in TA patients versus 2,037 mm(3) in controls, P < 0.05; wall:outer wall ratio 48% in TA patients versus 32% in controls, P < 0.001). The lumen volume was reduced in TA (1,224 mm(3) versus 1,398 mm(3) in controls, P < 0.05). In TA, LV function was more dynamic, with reduced end-systolic volume (mean +/- 95% confidence interval ejection fraction 74 +/- 3% versus 67 +/- 1% in controls, P < 0.001; LV end-systolic volume 19 +/- 4 ml/m(2) versus 25 +/- 1 ml/m(2) in controls, P < 0.001). Myocardial late gadolinium enhancement was present in 4 (27%) of 15 patients, indicating previously unrecognized myocardial damage. CONCLUSION: Our findings indicate that an integrated method of cardiovascular assessment by CMR in TA not only provides good delineation of vessel wall thickening, but has also demonstrated dynamic ventricular function, myocardial scarring, and silent myocardial infarction. CMR has benefits compared with other approaches for the assessment and followup of patients with TA, and has potential to identify patients most at risk of complications, allowing early preventative therapy.


Subject(s)
Carotid Arteries/pathology , Heart Ventricles/pathology , Magnetic Resonance Imaging/methods , Myocardium/pathology , Takayasu Arteritis/pathology , Adult , Aged , Case-Control Studies , Cohort Studies , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Myocardial Infarction/pathology , Myocardial Infarction/physiopathology , Prospective Studies , Regression Analysis , Stroke Volume/physiology , Ventricular Dysfunction, Left/pathology , Ventricular Dysfunction, Left/physiopathology
16.
Nat Clin Pract Cardiovasc Med ; 5(3): 169-74, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18212772

ABSTRACT

BACKGROUND: A previously fit and healthy 30-year-old man reported experiencing palpitations accompanied by nausea, sweating and presyncope. These symptoms were found to be associated with episodes of nonsustained ventricular tachycardia. He was a nonsmoker, did not drink excessively, denied illicit drug use and had no family history of structural cardiac disease or sudden death. INVESTIGATIONS: Electrocardiography, laboratory tests, electrophysiological studies, echocardiography, coronary angiography, chest radiography, cardiac MRI (with late gadolinium enhancement), chest CT, lymph-node biopsy, Ziehl Nielsen staining, blood and sputum cultures and heaf testing. DIAGNOSIS: Tubercular myocarditis. MANAGEMENT: Antituberculous chemotherapy supported by antiarrhythmic and steroid pharmacotherapy and cardioverter-defibrillator implantation. Repeated imaging was performed to monitor disease progression.


Subject(s)
Myocarditis/drug therapy , Myocarditis/microbiology , Tachycardia, Ventricular/diagnosis , Tuberculosis, Cardiovascular/diagnosis , Adult , Antitubercular Agents/therapeutic use , Diagnosis, Differential , Electrocardiography , Emergency Service, Hospital , Follow-Up Studies , Gadolinium , Humans , Magnetic Resonance Imaging , Male , Myocarditis/diagnosis , Risk Assessment , Severity of Illness Index , Tachycardia, Ventricular/therapy , Tomography, X-Ray Computed , Treatment Outcome , Tuberculosis, Cardiovascular/drug therapy
17.
J Magn Reson Imaging ; 26(6): 1444-51, 2007 Dec.
Article in English | MEDLINE | ID: mdl-17968886

ABSTRACT

PURPOSE: To directly compare the three main myocardial perfusion cardiovascular magnetic resonance (CMR) sequences incorporating parallel acquisition methods. MATERIALS AND METHODS: In 15 subjects (12 men, 57 +/- 15.7 years) referred for diagnostic coronary angiography, we acquired first-pass perfusion images (0.1 mmol/kg gadolinium-DTPA) at rest and during adenosine (140 microg/kg/min) on three separate occasions using three sequences incorporating parallel acquisition methods and approximately equivalent spatiotemporal resolution: hybrid echo planar imaging (hEPI), steady-state free precession (SSFP), and gradient echo imaging (GRE). We calculated the contrast-to-noise ratio (CNR) of each scan and blinded observers scored the presence and severity of artifacts (1, worst to 4, best), diagnostic confidence (0, low to 2, high), transmurality, area, and epicardial vessel territory of perfusion defects. RESULTS: CNR was greatest with SSFP and least with hEPI (13.15 vs 7.85 P < 0.001). The most artifacts were recorded with SSFP and least with hEPI (2.00 vs 3.03 P < 0.001). Observers were significantly more confident in reporting hEPI images (1.6 hEPI vs 0.9 SSFP, P < 0.001). Results for GRE were intermediate for all assessments. CONCLUSION: The hEPI sequence scored best for diagnostic performance despite the SSFP sequence having greater CNR. This trial favors hEPI for clinical myocardial perfusion CMR and suggests CNR should not be the sole criterion used to gauge the best candidate sequence.


Subject(s)
Coronary Vessels/anatomy & histology , Magnetic Resonance Imaging/methods , Artifacts , Contrast Media , Female , Gadolinium DTPA , Humans , Image Enhancement , Image Interpretation, Computer-Assisted , Male , Middle Aged
19.
Eur Heart J ; 28(10): 1242-9, 2007 May.
Article in English | MEDLINE | ID: mdl-17478458

ABSTRACT

AIMS: Troponin measurement is used in the assessment and risk stratification of patients presenting acutely with chest pain when the main cause of elevation is coronary artery disease. However, some patients have no coronary obstruction on angiography, leading to diagnostic uncertainty. We evaluated the incremental diagnostic value of cardiovascular magnetic resonance (CMR) in these patients. METHODS AND RESULTS: Sixty consecutive patients (mean age 44 years, 72% male) with a troponin-positive episode of chest pain and unobstructed coronary arteries were recruited within 3 months of initial presentation. All patients underwent CMR with cine imaging, T2-weighted imaging for detection of inflammation, and late gadolinium enhancement imaging for detection of infarction/fibrosis. An identifiable basis for troponin elevation was established in 65% of patients. The commonest underlying cause was myocarditis (50%), followed by myocardial infarction (11.6%) and cardiomyopathy (3.4%). In the 35% of patients where no clear diagnosis was identified by CMR, significant myocardial infarction/fibrosis was excluded. CONCLUSION: CMR is a valuable adjunct to conventional investigations in a diagnostically challenging and important group of patients with troponin-positive chest pain and unobstructed coronary arteries.


Subject(s)
Chest Pain/etiology , Heart Diseases/diagnosis , Adult , Biomarkers/blood , Cardiomyopathy, Dilated/complications , Cardiomyopathy, Dilated/diagnosis , Contrast Media , Female , Gadolinium DTPA , Heart Diseases/complications , Humans , Image Enhancement/methods , London , Magnetic Resonance Imaging, Cine/methods , Male , Middle Aged , Myocardial Infarction/complications , Myocarditis/complications , Myocarditis/diagnosis , Prospective Studies , Takotsubo Cardiomyopathy/complications , Takotsubo Cardiomyopathy/diagnosis , Troponin/blood
20.
Curr Cardiol Rep ; 9(1): 51-6, 2007 Mar.
Article in English | MEDLINE | ID: mdl-17362685

ABSTRACT

Hypertrophic cardiomyopathy (HCM) is an inherited cardiac disorder characterized by unexplained myocardial hypertrophy. The condition is associated with sudden cardiac death and is therefore often diagnosed postmortem, especially in the young and in competitive athletes. For this reason, intense research focuses on developing strategies to minimize this tragic consequence. Cardiovascular magnetic resonance (CMR) is a novel imaging modality that provides high-resolution images in an infinite number of planes with additional sequences that allows for tissue characterization and quantification of flow. The most exciting development is the application of late gadolinium-enhanced (LGE) imaging, which allows for in vivo detection of myocardial fibrosis. This review summarizes the current applications of CMR in HCM and also speculates on future applications, particularly the potential for risk stratification using LGE-CMR.


Subject(s)
Cardiomyopathy, Hypertrophic/diagnosis , Cardiomyopathy, Hypertrophic/therapy , Magnetic Resonance Imaging, Cine , Cardiomyopathy, Hypertrophic/complications , Cardiomyopathy, Hypertrophic/physiopathology , Contrast Media , Death, Sudden, Cardiac/epidemiology , Death, Sudden, Cardiac/etiology , Diagnosis, Differential , Endomyocardial Fibrosis/diagnosis , Gadolinium DTPA , Humans , Magnetic Resonance Imaging, Cine/trends , Risk Factors , Stroke Volume , Ventricular Outflow Obstruction/diagnosis , Ventricular Outflow Obstruction/physiopathology
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