Andrew M. Crean

Prognostic Value of Quantitative Contrast-Enhanced Cardiovascular Magnetic Resonance for the Evaluation of Sudden Death Risk in Patients With Hypertrophic Cardiomyopathy

Background— Hypertrophic cardiomyopathy (HCM) is the most common cause of sudden death in the young, although not all patients eligible for sudden death prevention with an implantable cardioverter-defibrillator are identified. Contrast-enhanced cardiovascular magnetic resonance with late gadolinium enhancement (LGE) has emerged as an in vivo marker of myocardial fibrosis, although its role in stratifying sudden death risk in subgroups of HCM patients remains incompletely understood. Methods and Results— We assessed the relation between LGE and cardiovascular outcomes in 1293 HCM patients referred for cardiovascular magnetic resonance and followed up for a median of 3.3 years. Sudden cardiac death (SCD) events (including appropriate defibrillator interventions) occurred in 37 patients (3%). A continuous relationship was evident between LGE by percent left ventricular mass and SCD event risk in HCM patients (P=0.001). Extent of LGE was associated with an increased risk of SCD events (adjusted hazard ratio, 1.46/10% increase in LGE; P=0.002), even after adjustment for other relevant disease variables. LGE of ≥15% of LV mass demonstrated a 2-fold increase in SCD event risk in those patients otherwise considered to be at lower risk, with an estimated likelihood for SCD events of 6% at 5 years. Performance of the SCD event risk model was enhanced by LGE (net reclassification index, 12.9%; 95% confidence interval, 0.3–38.3). Absence of LGE was associated with lower risk for SCD events (adjusted hazard ratio, 0.39; P=0.02). Extent of LGE also predicted the development of end-stage HCM with systolic dysfunction (adjusted hazard ratio, 1.80/10% increase in LGE; P<0.03). Conclusions— Extensive LGE measured by quantitative contrast enhanced CMR provides additional information for assessing SCD event risk among HCM patients, particularly patients otherwise judged to be at low risk.

Myocardial fibrosis in hypertrophic cardiomyopathy: accurate reflection of histopathological findings by CMR.

OBJECTIVES In this study we sought to explore the relationship between cardiac magnetic resonance (CMR) with late gadolinium enhancement (LGE) and histopathological parameters including interstitial fibrosis and replacement fibrosis (scar) in patients with hypertrophic cardiomyopathy (HCM). BACKGROUND CMR-LGE is a well-established tool for the assessment of scar in ischemic heart disease. Its role in HCM has evolved in recent years, and an association with nonsustained ventricular tachycardia has been demonstrated. METHODS HCM patients who underwent septal myectomy during the period 2004 through 2010 and had undergone CMR-LGE no more than 6 months before surgery were selected. Histopathological assessment of the myectomy specimens included quantitative digital analysis (interstitial and replacement fibrosis) and semiquantitative assessment (small intramural coronary arteriole dysplasia and disarray). Correlations between CMR-LGE measured with various techniques, SD above the signal intensity for the normal remote myocardium (2, 4, 5, 6, and 10 SD) and the full width at half maximum (FWHM) technique, at the myectomy site, and interstitial fibrosis, replacement fibrosis (scar), and their sum (fibrosis + scar) were evaluated. RESULTS Twenty-nine patients were included. Statistically significant correlations between CMR-LGE (at 2, 4, 5, 6, 10 SD and by the FWHM technique), and both interstitial fibrosis and the combined interstitial and replacement fibrosis were found. The strongest correlation was between combined interstitial and replacement fibrosis and CMR-LGE measured at 5 SD (r = 0.78, p < 0.0001). LGE measured at 10 SD demonstrated the best correlation with replacement fibrosis (r = 0.42, p = 0.02). Bland-Altman analysis revealed optimum agreement between the combined interstitial and replacement fibrosis found at pathology and LGE measured at 4 SD. In addition, moderate and severe small intramural coronary artery dysplasia showed a statistically significant correlation with replacement fibrosis (p = 0.01) and CMR-LGE at 10 SD (p = 0.04). CONCLUSIONS CMR-LGE measured at 4 SD and 5 SD yields the closest approximation to the extent of total fibrosis measured by the histopathological standard of reference. These findings have implications for future investigations of CMR-LGE and its association with important clinical endpoints in HCM, including sudden cardiac death.

Investigation of Global and Regional Myocardial Mechanics With 3-Dimensional Speckle Tracking Echocardiography and Relations to Hypertrophy and Fibrosis in Hypertrophic Cardiomyopathy

Background—In hypertrophic cardiomyopathy (HCM), heterogeneous myocardial hypertrophy and fibrosis are responsible for abnormalities of left ventricular (LV) function. We aimed to characterize LV global and regional myocardial mechanics in HCM, according to segmental hypertrophy and fibrosis. Methods and Results—Fifty-nine patients with HCM underwent standard echocardiography, 3-dimensional speckle tracking echocardiography, and cardiac magnetic resonance with late gadolinium enhancement (LGE); all 3 tests were <24 hours apart. Longitudinal, circumferential, and area strains were investigated according to the extent of LGE (no LGE, LGE<10%, and LGE≥10%), segmental thickness (≥15 versus <15 mm), and segmental LGE (LGE versus non-LGE). Attenuated global longitudinal strain showed association with extent of hypertrophy (indexed LV mass, r=0.32, P=0.01; maximum LV wall thickness, r=0.34, P=0.009; number of segments ≥15 mm, r=0.44, P<0.001), whereas enhanced global circumferential strain was correlated to LV global functional parameters (indexed end-systolic volume, r=0.47, P<0.001; ejection fraction, r=−0.75, P<0.001). Parameters of global myocardial mechanics showed no association with the extent of LGE; in contrast, the extent of LGE was associated with the extent of hypertrophy. All 3 deformation parameters were attenuated both in segments ≥15 mm in thickness and in those with LGE; adjusted analysis demonstrated that segmental presence of LGE was associated with additional attenuation in myocardial deformation. Conclusions—Both hypertrophy and fibrosis contribute to regional impairment of myocardial shortening in HCM. The extent of hypertrophy is the primary factor altering global myocardial mechanics. Circumferential myocardial shortening seems to be directly involved in preservation of LV systolic performance in HCM.

3D Echo systematically underestimates right ventricular volumes compared to cardiovascular magnetic resonance in adult congenital heart disease patients with moderate or severe RV dilatation

BackgroundThree dimensional echo is a relatively new technique which may offer a rapid alternative for the examination of the right heart. However its role in patients with non-standard ventricular size or anatomy is unclear. This study compared volumetric measurements of the right ventricle in 25 patients with adult congenital heart disease using both cardiovascular magnetic resonance (CMR) and three dimensional echocardiography.MethodsPatients were grouped by diagnosis into those expected to have normal or near-normal RV size (patients with repaired coarctation of the aorta) and patients expected to have moderate or worse RV enlargement (patients with repaired tetralogy of Fallot or transposition of the great arteries). Right ventricular end diastolic volume, end systolic volume and ejection fraction were compared using both methods with CMR regarded as the reference standardResultsBland-Altman analysis of the 25 patients demonstrated that for both RV EDV and RV ESV, there was a significant and systematic under-estimation of volume by 3D echo compared to CMR. This bias led to a mean underestimation of RV EDV by -34% (95%CI: -91% to + 23%). The degree of underestimation was more marked for RV ESV with a bias of -42% (95%CI: -117% to + 32%). There was also a tendency to overestimate RV EF by 3D echo with a bias of approximately 13% (95% CI -52% to +27%).ConclusionsStatistically significant and clinically meaningful differences in volumetric measurements were observed between the two techniques. Three dimensional echocardiography does not appear ready for routine clinical use in RV assessment in congenital heart disease patients with more than mild RV dilatation at the current time.

Cardiac Magnetic Resonance Imaging and the Assessment of Ebstein Anomaly in Adults

No published studies have evaluated the role of cardiac magnetic resonance (CMR) imaging for the assessment of Ebstein anomaly. Our objective was to evaluate the right heart characteristics in adults with unrepaired Ebstein anomaly using contemporary CMR imaging techniques. Consecutive patients with unrepaired Ebstein anomaly and complete CMR studies from 2004 to 2009 were identified (n = 32). Volumetric measurements were obtained from the short-axis and axial views, including assessment of the functional right ventricular (RV) end-diastolic volume (EDV) and end-systolic volume. The volume of the atrialized portion of the right ventricle in end-diastole was calculated as the difference between the total RVEDV and the functional RVEDV. The reproducibility of the measurements in the axial and short-axis views was determined within and between observers. The median value derived from the short-axis and axial views was 136 ml/m(2) (range 59 to 347) and 136 ml/m(2) (range 63 to 342) for the functional RVEDV, 153 ml/m(2) (range 64 to 441) and 154 ml/m(2) (range 67 to 436) for the total RVEDV, 49% (range 32% to 46%) and 50% (range 40% to 64%) for the functional RV ejection fraction, respectively. The axial measurements demonstrated lower intraobserver and interobserver variability than the short-axis approach for all values, with the exception of the intraobserver functional RVEDV and interobserver total RVEDV for which the limits of agreement and variance were not significantly different between the 2 views. In conclusion, measurements of right heart size and systolic function in patients with Ebstein anomaly can be reliably achieved using CMR imaging. Axial imaging appeared to provide more reproducible data than that obtained from the short-axis views.

Visualization of coronary venous anatomy by cardiovascular magnetic resonance

BackgroundCoronary venous imaging with whole-heart cardiovascular magnetic resonance (CMR) angiography has recently been described using developmental pulse sequences and intravascular contrast agents. However, the practical utility of coronary venous imaging will be for patients with heart failure in whom cardiac resynchronisation therapy (CRT) is being considered. As such complementary information on ventricular function and myocardial viability will be required. The aim of this study was to determine if the coronary venous anatomy could be depicted as part of a comprehensive CMR protocol and using a standard extracellular contrast agent.Methods and ResultsThirty-one 3D whole heart CMR studies, performed after intravenous administration of 0.05 mmol/kg gadolinium DTPA, were reviewed. The cardiac venous system was visualized in all patients. The lateral vein of the left ventricle was present in 74%, the anterior interventricular vein in 65%, and the posterior interventricular vein in 74% of patients. The mean maximum distance of demonstrable cardiac vein on the 3D images was 81.5 mm and was dependent on the quality of the 3D data set. Five patients showed evidence of myocardial infarction on late gadolinium enhancement (LGE) images.ConclusionCoronary venous anatomy can be reliably demonstrated using a comprehensive CMR protocol and a standard extracellular contrast agent. The combination of coronary venous imaging, assessment of ventricular function and LGE may be useful in the management of patients with LV dysfunction being considered for CRT.

Percutaneous Pulmonary Valve Implantation: 5 Years of Follow-Up Does Age Influence Outcomes?

Background—Percutaneous pulmonary valve implantation (PPVI) is a safe, less invasive alternative to surgical valve replacement for the congenital heart disease patient with right ventricular (RV) outflow tract dysfunction. The aim of this study was to determine whether reverse RV remodeling after PPVI was persistent in the longer term and whether timing of PPVI influenced outcomes. Methods and Results—Consecutive patients from the pediatric and adult congenital heart disease programs were enrolled. Cardiac MRI, echocardiography, metabolic exercise testing, chest radiography, and hemodynamics before intervention were compared with repeated follow-up measurements to assess changes over time. Fifty-one patients (including 23 patients <16 years old) were followed for a mean 4.5±1.9 (0.9–6.9) years after implantation, 59% of patients having available comparative cardiac MRI data. Freedom from any reintervention was 87% and 68% at 3 and 5 years, and freedom from surgery was 90% at 5 years. For every decade younger at implantation, there was an increase of 3.9%±1.0% in cardiac MRI left ventricular ejection fraction (P<0.001) and 2.4±0.9 mL/kg/min in maxVO2 (P=0.005) and a decrease of 0.7±0.2 cm in RV end-diastolic dimension (P<0.001) after intervention. Younger patients displayed an additional decline in the RV/left ventricular end-diastolic volume ratio (P=0.05) and trended toward improved RV ejection fraction in late follow-up (50%±7% versus 41%±12%, P=0.07). Conclusions—This is the largest series to show that PPVI at a younger age yields incremental improvements in RV size and maximum oxygen consumption. Early valve implantation is associated with better RV function and should be considered in management planning for this population.

Relationship of dysglycemia to acute myocardial infarct size and cardiovascular outcome as determined by cardiovascular magnetic resonance

BackgroundImproved outcomes for normoglycemic patients suffering acute myocardial infarction (AMI) over the last decade have not been matched by similar improvements in mortality for diabetic patients despite similar levels of baseline risk and appropriate medical therapy. Two of the major determinants of poor outcome following AMI are infarct size and left ventricular (LV) dysfunction.MethodsNinety-three patients with first AMI were studied. 22 patients had diabetes mellitus (DM) based on prior history or admission blood glucose ≥11.1 mmol/l. 13 patients had dysglycemia (admission blood glucose ≥7.8 mmol/l but <11.1 mmol/l) and 58 patients had normoglycemia (admission blood glucose <7.8 mmol/l). Patients underwent cardiac magnetic resonance (CMR) imaging at index presentation and median follow-up of 11 months. Cine imaging assessed LV function and late gadolinium contrast-enhanced imaging was used to quantify infarct size. Clinical outcome data were collected at 18 months median follow-up.ResultsPatients with dysglycemia and DM had larger infarct sizes by CMR than normoglycemic patients; at baseline percentage LV scar (mean (SD)) was 23.0% (10.9), 25.6% (12.9) and 15.8% (10.3) respectively (p = 0.001), and at 11 months percentage LV scar was 17.6% (8.9), 19.1% (9.6) and 12.4% (7.8) (p = 0.017). Patients with dysglycemia and DM also had lower event-free survival at 18 months (p = 0.005).ConclusionsPatients with dysglycemia or diabetes mellitus sustain larger infarct sizes than normoglycemic patients, as determined by CMR. This may, in part, account for their adverse prognosis following AMI.

The left heart after pulmonary valve replacement in adults late after tetralogy of Fallot repair.

BACKGROUND Adverse ventricular-ventricular interactions have been recognized in those with repaired tetralogy of Fallot (TOF) and severe pulmonary regurgitation. OBJECTIVE We aimed to examine the impact of pulmonary valve replacement (PVR) on the left heart late after TOF repair. METHODS AND RESULTS Left ventricular (LV) volumes and ejection fractions (EF) were analyzed in adults with severe pulmonary regurgitation after TOF repair with cardiac magnetic resonance imaging (CMR) before and after PVR. Thirty-nine patients (median age 33[20-65] years) were reviewed. Post-PVR, LVEF improved significantly in the entire cohort (50 ± 9%→54 ± 7%, p<0.001) and in those with moderately impaired (defined as LVEF ≤ 45%) preoperative LVEF (38 ± 5%→47 ± 6%, p<0.0001), but was not statistically different in those with relatively preserved (defined as LVEF >45%) preoperative LVEF. By multivariate linear regression analysis to evaluate independent CMR predictors of improved LVEF post-PVR for the entire cohort, the only CMR variable to emerge was preoperative LVEF (p=0.012, regression coefficient -0.54, SE 0.13). Whereas PVR resulted in increased LV filling in patients with relatively preserved preoperative LVEF reflected by an increase in LV end-diastolic volumes (77 ± 10→82 ± 16 mL/m(2), p=0.05), LV end-systolic volumes decreased after PVR in patients with impaired preoperative LVEF (65 ± 12→54 ± 10 mL/m(2), p=0.001) but LV end-diastolic volumes were not significantly changed. CONCLUSION When LVEF is decreased after TOF repair, PVR appears to have a salutary effect on postoperative LVEF, thereby supporting the concept of recovery of adverse right-left heart interactions. Mechanisms of left heart improvement post-PVR differ depending on degree of preoperative LV systolic dysfunction.

Echocardiography for Assessment of Right Ventricular Volumes Revisited: A Cardiac Magnetic Resonance Comparison Study in Adults with Repaired Tetralogy of Fallot

BACKGROUND The aim of this study was to develop a mathematical model using two-dimensional echocardiographic parameters to estimate right ventricular end-diastolic volume (RVEDVi) in adults with repaired tetralogy of Fallot. METHODS Linear regression equations were used to examine the relationship between two-dimensional echocardiographic and cardiac magnetic resonance (CMR) imaging measures of RVEDVi. Imaging studies in 101 adults were used to create and validate the model. The ability of the model to detect changes in CMR RVEDVi was tested in 57 adults with serial studies. RESULTS The optimal model to quantitate CMR RVEDVi included two-dimensional echocardiographic right ventricular end-diastolic area measured in the apical four-chamber view, indexed to body surface area (AreaDi) (CMR RVEDVi = 11.5 + [7 x AreaDi]). The model reliably allowed the detection of stable and changing CMR RVEDVi (kappa = 0.84 and kappa = 0.82, respectively, P < .0001). CONCLUSION Quantitative assessment of right-ventricular volumes by echocardiography is feasible and may be used for serial follow-up in patients with contraindications for CMR.