Gerald Carr-White

Native T1 Mapping in Differentiation of Normal Myocardium From Diffuse Disease in Hypertrophic and Dilated Cardiomyopathy

OBJECTIVESnThe aim of this study was to examine the value of native and post-contrast T1 relaxation in the differentiation between healthy and diffusely diseased myocardium in 2 model conditions, hypertrophic cardiomyopathy and nonischemic dilated cardiomyopathy.nnnBACKGROUNDnT1 mapping has been proposed as potentially valuable in the quantitative assessment of diffuse myocardial fibrosis, but no studies to date have systematically evaluated its role in the differentiation of healthy myocardium from diffuse disease in a clinical setting.nnnMETHODSnConsecutive subjects undergoing routine clinical cardiac magnetic resonance at Kings College London were invited to participate in this study. Groups were based on cardiac magnetic resonance findings and consisted of subjects with known hypertrophic cardiomyopathy (n = 25) and nonischemic dilated cardiomyopathy (n = 27). Thirty normotensive subjects with low pre-test likelihood of cardiomyopathy, not taking any regular medications and with normal cardiac magnetic resonance findings including normal left ventricular mass indexes, served as controls. Single equatorial short-axis slice T1 mapping was performed using a 3-T scanner before and at 10, 20, and 30 minutes after the administration of 0.2 mmol/kg of gadobutrol. T1 values were quantified within the septal myocardium (T1 native), and extracellular volume fractions (ECV) were calculated.nnnRESULTSnT1 native was significantly longer in patients with cardiomyopathy compared with control subjects (p < 0.01). Conversely, post-contrast T1 values were significantly shorter in patients with cardiomyopathy at all time points (p < 0.01). ECV was significantly higher in patients with cardiomyopathy compared with controls at all time points (p < 0.01). Multivariate binary logistic regression revealed that T1 native could differentiate between healthy and diseased myocardium with sensitivity of 100%, specificity of 96%, and diagnostic accuracy of 98% (area under the curve 0.99; 95% confidence interval: 0.96 to 1.00; p < 0.001), whereas post-contrast T1 values and ECV showed lower discriminatory performance.nnnCONCLUSIONSnThis study demonstrates that native and post-contrast T1 values provide indexes with high diagnostic accuracy for the discrimination of normal and diffusely diseased myocardium.

Native Myocardial T1 Mapping by Cardiovascular Magnetic Resonance Imaging in Subclinical Cardiomyopathy in Patients With Systemic Lupus Erythematosus

Background— Increased systemic inflammation has been linked to myocardial dysfunction and heart failure in patients with systemic lupus erythematosus (SLE). Accurate detection of early myocardial changes may be able to guide preventive intervention. We investigated whether multiparametric imaging by cardiovascular magnetic resonance can detect differences between controls and asymptomatic SLE patients. Methods and Results— A total of 33 SLE predominantly female patients (mean age, 40±9 years) underwent cardiovascular magnetic resonance for routine assessment of myocardial perfusion, function, and late gadolinium enhancement. T1 mapping was performed in single short-axis slice before and after 15 minutes of gadolinium administration. Twenty-one subjects with a low pretest probability and normal cardiovascular magnetic resonance served as a control group. Both groups had similar left ventricular volumes and mass and normal global systolic function. SLE patients had significantly reduced longitudinal strain (controls versus SLE, −20±2% versus −17±3%; P<0.01) and showed intramyocardial and pericardial late gadolinium enhancement. SLE patients had significantly increased native myocardial T1 (1056±27 versus 1152±46 milliseconds; P<0.001) and extracellular volume fraction (26±5% versus 30±6%; P=0.007) and reduced postcontrast myocardial T1 (454±53 versus 411±62 milliseconds; P=0.01). T1-derived indices were associated with longitudinal strain (r=0.37–0.47) but not with the presence of late gadolinium enhancement. Native myocardial T1 values showed the greatest concordance with the presence of clinical diagnosis of SLE. Conclusions— In patients with SLE who are free of cardiac symptoms, there is evidence of subclinical perimyocardial impairment. We further demonstrate that T1 mapping may have potential to detect subclinical myocardial involvement in patients with SLE.

Prevalence of Desmosomal Protein Gene Mutations in Patients With Dilated Cardiomyopathy

Background—Idiopathic dilated cardiomyopathy is a familial disorder in 25% to 50% of patients, but the genetic basis in the majority of cases remains unknown. Genes encoding desmosomal proteins, currently regarded as synonymous with another disorder, arrhythmogenic right ventricular cardiomyopathy, are known to cause left ventricular dysfunction, but their importance in unselected patients with unequivocal dilated cardiomyopathy is unknown. The objective of this study was to determine the prevalence of mutations in 5 desmosomal protein genes in patients with dilated cardiomyopathy. Methods and Results—We studied 100 unrelated patients with idiopathic dilated cardiomyopathy consecutively referred to a dedicated cardiomyopathy unit. Patients underwent clinical evaluation, ECG, echocardiography, exercise testing, 24-hour ambulatory ECG monitoring, and mutation screening of 5 genes implicated in arrhythmogenic right ventricular cardiomyopathy: plakoglobin, desmoplakin, plakophilin-2, desmoglein-2, and desmocollin-2. Of the 100 patients (mean age at evaluation, 46.8±13.8 years; range, 17.0 to 72.8 years; male sex, 63%), 5 were found to carry pathogenic desmosomal protein gene mutations. An additional 13 patients had sequence variants of uncertain pathogenic significance and were excluded from further comparative analysis. Patients harboring desmosomal gene mutations had a phenotype indistinguishable from the 82 noncarriers, with the exception of exercise-induced ventricular ectopy, which was more frequent in the desmosomal mutation carriers (P=0.033). None of the 5 carriers of desmosomal mutations fulfilled current diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy, but 1 had fibrofatty change in the left ventricle at autopsy. Conclusions—Heart failure caused by a dilated, poorly contracting left ventricle and arrhythmogenic right ventricular cardiomyopathy have been considered distinct clinicopathologic entities. This study suggests that both clinical presentations can be caused by mutations in desmosomal protein genes.

Intraoperative cardiac troponin T release and lactate metabolism during coronary artery surgery: comparison of beating heart with conventional coronary artery surgery with cardiopulmonary bypass

OBJECTIVE To compare cardiac troponin T release and lactate metabolism in coronary sinus and arterial blood during uncomplicated coronary grafting on the beating heart with conventional coronary grafting using cardiopulmonary bypass. DESIGN A prospective observational study with simultaneous sampling of coronary sinus and arterial blood: before and 1, 4, 10, and 20 minutes after reperfusion for analysis of cardiac troponin T and lactate. Cardiac troponin T was also analysed in venous samples taken 3, 6, 24, 48, and 72 hours after surgery. SETTING Cardiac surgical unit in a tertiary referral centre. PATIENTS 18 patients undergoing coronary grafting on the beating heart (10 single vessel and eight two-vessel grafting) and eight undergoing two-vessel grafting with cardiopulmonary bypass. RESULTS Cardiac troponin T was detected in coronary sinus blood in all patients by 20 minutes after beating heart coronary artery surgery before arterial concentrations were consistently increased. Peak arterial and coronary sinus cardiac troponin T values on the beating heart during single (0.03 (0 to 0.05) and 0.09 (0.07 to 0.16 μg/l, respectively) and two-vessel grafting (0.1 (0.07 to 0.11) and 0.19 (0.14 to 0.25) μg/l) were lower than the values obtained during cardiopulmonary bypass (0.64 (0.52 to 0.72) and 1.4 (0.9 to 2.0) μg/l) (pu2009<u20090.05). The area under the curve of venous cardiac troponin T over 72 hours for two-vessel grafting on the beating heart was less than with cardiopulmonary bypass (13 (10 to 16) v 68 (26 to 102) μg.h/l) (pu2009<u20090.001). Lactate extraction began within one minute of snare release during beating heart coronary surgery while lactate was still being produced 20 minutes after cross clamp release following cardiopulmonary bypass. CONCLUSIONS Lower intraoperative and serial venous cardiac troponin T concentrations suggest a lesser degree of myocyte injury during beating heart coronary artery surgery than during cardiopulmonary bypass. Oxidative metabolism also recovers more rapidly with beating heart coronary artery surgery than with conventional coronary grafting. Coronary sinus cardiac troponin T concentrations increased earlier and were greater than arterial concentrations during beating heart surgery, suggesting that this may be a more sensitive method of intraoperative assessment of myocardial injury.

Benchmarking framework for myocardial tracking and deformation algorithms: An open access database

In this paper we present a benchmarking framework for the validation of cardiac motion analysis algorithms. The reported methods are the response to an open challenge that was issued to the medical imaging community through a MICCAI workshop. The database included magnetic resonance (MR) and 3D ultrasound (3DUS) datasets from a dynamic phantom and 15 healthy volunteers. Participants processed 3D tagged MR datasets (3DTAG), cine steady state free precession MR datasets (SSFP) and 3DUS datasets, amounting to 1158 image volumes. Ground-truth for motion tracking was based on 12 landmarks (4 walls at 3 ventricular levels). They were manually tracked by two observers in the 3DTAG data over the whole cardiac cycle, using an in-house application with 4D visualization capabilities. The median of the inter-observer variability was computed for the phantom dataset (0.77 mm) and for the volunteer datasets (0.84 mm). The ground-truth was registered to 3DUS coordinates using a point based similarity transform. Four institutions responded to the challenge by providing motion estimates for the data: Fraunhofer MEVIS (MEVIS), Bremen, Germany; Imperial College London - University College London (IUCL), UK; Universitat Pompeu Fabra (UPF), Barcelona, Spain; Inria-Asclepios project (INRIA), France. Details on the implementation and evaluation of the four methodologies are presented in this manuscript. The manually tracked landmarks were used to evaluate tracking accuracy of all methodologies. For 3DTAG, median values were computed over all time frames for the phantom dataset (MEVIS=1.20mm, IUCL=0.73 mm, UPF=1.10mm, INRIA=1.09 mm) and for the volunteer datasets (MEVIS=1.33 mm, IUCL=1.52 mm, UPF=1.09 mm, INRIA=1.32 mm). For 3DUS, median values were computed at end diastole and end systole for the phantom dataset (MEVIS=4.40 mm, UPF=3.48 mm, INRIA=4.78 mm) and for the volunteer datasets (MEVIS=3.51 mm, UPF=3.71 mm, INRIA=4.07 mm). For SSFP, median values were computed at end diastole and end systole for the phantom dataset(UPF=6.18 mm, INRIA=3.93 mm) and for the volunteer datasets (UPF=3.09 mm, INRIA=4.78 mm). Finally, strain curves were generated and qualitatively compared. Good agreement was found between the different modalities and methodologies, except for radial strain that showed a high variability in cases of lower image quality.

A Simultaneous X-Ray/MRI and Noncontact Mapping Study of the Acute Hemodynamic Effect of Left Ventricular Endocardial and Epicardial Cardiac Resynchronization Therapy in Humans

Background—Cardiac resynchronization therapy (CRT) using endocardial left ventricular (LV) pacing may be superior to conventional CRT. We studied the acute hemodynamic response to conventional CRT and LV pacing from different endocardial sites using a combined cardiac MRI and LV noncontact mapping (NCM) protocol to gain insights into the underlying mechanisms. Methods and Results—Fifteen patients (age, 63±10 years; 12 men) awaiting CRT were studied in a combined x-ray and MRI laboratory. Delayed-enhancement cardiac magnetic resonance was performed to define areas of myocardial fibrosis. Patients underwent an electrophysiological study incorporating endocardial and epicardial LV pacing. Acute hemodynamic response was measured using a pressure wire within the LV cavity to derive LV dP/dt max. NCM was used to define areas of slow conduction. There was a significant improvement in all LV pacing modes versus baseline (P<0.001). LV endocardial CRT from the best endocardial site was superior to conventional CRT, with a 79.8±49.0% versus 59.6±49.5% increase in LV dP/dt max of from baseline (P<0.05). The hemodynamic benefits of pacing were greater when LV stimulation was performed outside of areas of slow conduction defined by NCM (P<0.001). Delayed-enhancement cardiac magnetic resonance was able to delineate zones of slow conduction seen with NCM in ischemic patients but was unreliable in nonischemic patients. Conclusions—Endocardial LV pacing appears superior to conventional CRT, although the optimal site varies between subjects and is influenced by pacing within areas of slow conduction. Delayed-enhancement cardiac magnetic resonance was a poor predictor of zones of slow conduction in nonischemic patients.

T1 Mapping in Discrimination of Hypertrophic Phenotypes: Hypertensive Heart Disease and Hypertrophic Cardiomyopathy Findings From the International T1 Multicenter Cardiovascular Magnetic Resonance Study

Background— The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects.nnMethods and Results— Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension ( P 15 mm ( P 2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls.nnConclusions— Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.Background—The differential diagnosis of left ventricular (LV) hypertrophy remains challenging in clinical practice, in particular, between hypertrophic cardiomyopathy (HCM) and increased LV wall thickness because of systemic hypertension. Diffuse myocardial disease is a characteristic feature in HCM, and an early manifestation of sarcomere–gene mutations in subexpressed family members (G+P− subjects). This study aimed to investigate whether detecting diffuse myocardial disease by T1 mapping can discriminate between HCM versus hypertensive heart disease as well as to detect genetically driven interstitial changes in the G+P− subjects. Methods and Results—Patients with diagnoses of HCM or hypertension (HCM, n=95; hypertension, n=69) and G+P− subjects (n=23) underwent a clinical cardiovascular magnetic resonance protocol (3 tesla) for cardiac volumes, function, and scar imaging. T1 mapping was performed before and >20 minutes after administration of 0.2 mmol/kg of gadobutrol. Native T1 and extracellular volume fraction were significantly higher in HCM compared with patients with hypertension (P<0.0001), including in subgroup comparisons of HCM subjects without evidence of late gadolinium enhancement, as well as of hypertensive patients LV wall thickness of >15 mm (P<0.0001). Compared with controls, native T1 was significantly higher in G+P− subjects (P<0.0001) and 65% of G+P− subjects had a native T1 value >2 SD above the mean of the normal range. Native T1 was an independent discriminator between HCM and hypertension, over and above extracellular volume fraction, LV wall thickness and indexed LV mass. Native T1 was also useful in separating G+P− subjects from controls. Conclusions—Native T1 may be applied to discriminate between HCM and hypertensive heart disease and detect early changes in G+P− subjects.

A comparison of left ventricular endocardial, multisite, and multipolar epicardial cardiac resynchronization: an acute haemodynamic and electroanatomical study

AIMSnAlternative forms of cardiac resynchronization therapy (CRT), including biventricular endocardial (BV-Endo) and multisite epicardial pacing (MSP), have been developed to improve response. It is unclear which form of stimulation is optimal. We aimed to compare the acute haemodynamic response (AHR) and electrophysiological effects of BV-Endo with MSP via two separate coronary sinus (CS) leads or a single-quadripolar CS lead.nnnMETHODS AND RESULTSnFifteen patients with a previously implanted CRT system received a second temporary CS lead and left ventricular (LV) endocardial catheter. A pressure wire and non-contact mapping array were placed into the LV cavity to measure LVdP/dtmax and perform electroanatomical mapping. Conventional CRT, BV-Endo, and MSP were then performed (MSP-1 via two epicardial leads and MSP-2 via a single-quadripolar lead). The best overall AHR was found using BV-Endo pacing with a 19.6 ± 13.6% increase in AHR at the optimal endocardial site over baseline (P < 0.001). There was an increase in LVdP/dtmax with MSP-1 and MSP-2 compared with conventional CRT, but this was not statistically significant. Biventricular endocardial pacing from the optimal site was significantly superior to conventional CRT (P = 0.039). The AHR achieved when BV-Endo pacing was highly site specific. Within individuals, the best pacing modality varied and was affected by the underlying substrate. Left ventricular activation times did not predict the optimal haemodynamic configuration.nnnCONCLUSIONnBiventricular endocardial pacing and not MSP was superior to conventional CRT, but was highly site specific. Within individuals, however, different methods of stimulation are optimal and may need to be tailored to the underlying substrate.

Benefits of endocardial and multisite pacing are dependent on the type of left ventricular electric activation pattern and presence of ischemic heart disease: insights from electroanatomic mapping.

Background—There is considerable heterogeneity in the myocardial substrate of patients undergoing cardiac resynchronization therapy (CRT), in particular in the etiology of heart failure and in the location of conduction block within the heart. This may account for variability in response to CRT. New approaches, including endocardial and multisite left ventricular (LV) stimulation, may improve CRT response. We sought to evaluate these approaches using noncontact mapping to understand the underlying mechanisms. Methods and Results—Ten patients (8 men and 2 women; mean [SD] age 63 [12] years; LV ejection fraction 246%; QRS duration 161 [24] ms) fulfilling conventional CRT criteria underwent an electrophysiological study, with assessment of acute hemodynamic response to conventional CRT as well as LV endocardial and multisite pacing. LV activation pattern was assessed using noncontact mapping. LV endocardial pacing gave a superior acute hemodynamic response compared with conventional CRT (26% versus 37% increase in LV dP/dtmax, respectively; P<0.0005). There was a trend toward further incremental benefit from multisite LV stimulation, although this did not reach statistical significance (P=0.08). The majority (71%) of patients with nonischemic heart failure etiology or functional block responded to conventional CRT, whereas those with myocardial scar or absence of functional block often required endocardial or multisite pacing to achieve CRT response. Conclusions—Endocardial or multisite pacing may be required in certain subsets of patients undergoing CRT. Patients with ischemic cardiomyopathy and those with narrower QRS, in particular, may stand to benefit.

Multi-site left ventricular pacing as a potential treatment for patients with postero-lateral scar: insights from cardiac magnetic resonance imaging and invasive haemodynamic assessment.

AIMSnMulti-site left ventricular (LV) pacing may be superior to single-site stimulation in correcting dyssynchrony and avoiding areas of myocardial scar. We sought to characterize myocardial scar using cardiac magnetic resonance imaging (CMR). We aimed to quantify the acute haemodynamic response to single-site and multi-site LV stimulation and to relate this to the position of the LV leads in relation to myocardial scar.nnnMETHODSnTwenty patients undergoing cardiac resynchronization therapy had implantation of two LV leads. One lead (LV1) was positioned in a postero-lateral vein, the second (LV2) in a separate coronary vein. LV dP/dtmax was recorded using a pressure wire during stimulation at LV1, LV2, and both sites simultaneously (LV1 + 2). Patients were deemed acute responders if ΔLV dP/dtmax was ≥ 10%. Cardiac magnetic resonance imaging was performed to assess dyssynchrony as well as location and burden of scar. Scar anatomy was registered with fluoroscopy to assess LV lead position in relation to scar.nnnRESULTSnLV dP/dtmax increased from 726 ± 161 mmHg/s in intrinsic rhythm to 912 ± 234 mmHg/s with LV1, 837 ± 188 mmHg/s with LV2, and 932 ± 201 mmHg/s with LV1 and LV2. Nine of 19 (47%) were acute responders with LV1 vs. 6/19 (32%) with LV2. Twelve of 19 (63%) were acute responders with simultaneous LV1 + 2. Two of three patients benefitting with multi-site pacing had the LV1 lead positioned in postero-lateral scar.nnnCONCLUSIONnMulti-site LV pacing increased acute response by 16% vs. single-site pacing. This was particularly beneficial in patients with postero-lateral scar identified on CMR.