James C. Moon

Automatic Measurement of the Myocardial Interstitium: Synthetic Extracellular Volume Quantification Without Hematocrit Sampling.

OBJECTIVESnThe authors sought to generate a synthetic extracellular volume fraction (ECV) from the relationship between hematocrit and longitudinal relaxation rate of blood.nnnBACKGROUNDnECV quantification by cardiac magnetic resonance (CMR) measures diagnostically and prognostically relevant changes in the extracellular space. Current methodologies require blood hematocrit (Hct) measurement-a complication to easy clinical application. We hypothesized that the relationship between Hct and longitudinal relaxation rate of blood (R1 = 1/T1blood) could be calibrated and used to generate a synthetic ECV without Hct that was valid, user-friendly, and prognostic.nnnMETHODSnProof-of-concept: 427 subjects with a wide range of health and disease were divided into derivation (n = 214) and validation (n = 213) cohorts. Histology cohort: 18 patients with severe aortic stenosis with histology obtained during valve replacement. Outcome cohort: For comparison with external outcome data, we applied synthetic ECV to 1,172 consecutive patients (median follow-up 1.7 years; 74 deaths). All underwent CMR scanning at 1.5-T with ECV calculation from pre- and post-contrast T1 (blood and myocardium) and venous Hct.nnnRESULTSnProof-of-concept: In the derivation cohort, native R1blood and Hct showed a linear relationship (R(2) = 0.51; p < 0.001), which was used to create synthetic Hct and ECV. Synthetic ECV correlated well with conventional ECV (R(2) = 0.97; p < 0.001) without bias. These results were maintained in the validation cohort. Histology cohort: Synthetic and conventional ECV both correlated well with collagen volume fraction measured from histology (R(2) = 0.61 and 0.69, both p < 0.001) with no statistical difference (p = 0.70). Outcome cohort: Synthetic ECV related to all-cause mortality (hazard ratio 1.90; 95% confidence interval 1.55 to 2.31; for every 5% increase in ECV). Finally, we engineered a synthetic ECV tool, generating automatic ECV maps during image acquisition.nnnCONCLUSIONSnSynthetic ECV provides validated noninvasive quantification of the myocardial extracellular space without blood sampling and is associated with cardiovascular outcomes.

Dark blood late enhancement imaging

BackgroundBright blood late gadolinium enhancement (LGE) imaging typically achieves excellent contrast between infarcted and normal myocardium. However, the contrast between the myocardial infarction (MI) and the blood pool is frequently suboptimal. A large fraction of infarctions caused by coronary artery disease are sub-endocardial and thus adjacent to the blood pool. It is not infrequent that sub-endocardial MIs are difficult to detect or clearly delineate.MethodsIn this present work, an inversion recovery (IR) T2 preparation was combined with single shot steady state free precession imaging and respiratory motion corrected averaging to achieve dark blood LGE images with good signal to noise ratio while maintaining the desired spatial and temporal resolution. In this manner, imaging was conducted free-breathing, which has benefits for image quality, patient comfort, and clinical workflow in both adults and children. Furthermore, by using a phase sensitive inversion recovery reconstruction the blood signal may be made darker than the myocardium (i.e., negative signal values) thereby providing contrast between the blood and both the MI and remote myocardium. In the proposed approach, a single T1-map scout was used to measure the myocardial and blood T1 using a MOdified Look-Locker Inversion recovery (MOLLI) protocol and all protocol parameters were automatically calculated from these values within the sequence thereby simplifying the user interface.ResultsThe contrast to noise ratio (CNR) between MI and remote myocardium was measured in nu2009=u200930 subjects with subendocardial MI using both bright blood and dark blood protocols. The CNR for the dark blood protocol had a 13xa0% loss compared to the bright blood protocol. The CNR between the MI and blood pool was positive for all dark blood cases, and was negative in 63xa0% of the bright blood cases. The conspicuity of subendocardial fibrosis and MI was greatly improved by dark blood (DB) PSIR as well as the delineation of the subendocardial border.ConclusionsFree-breathing, dark blood PSIR LGE imaging was demonstrated to improve the visualization of subendocardial MI and fibrosis in cases with low contrast with adjacent blood pool. The proposed method also improves visualization of thin walled fibrous structures such as atrial walls and valves, as well as papillary muscles.

Repeat doses of antibody to serum amyloid P component clear amyloid deposits in patients with systemic amyloidosis

Repeat cycles of miridesap, to deplete circulating serum amyloid P component (SAP), followed by the anti-SAP antibody, dezamizumab, cleared visceral amyloid deposits in patients with systemic amyloidosis. Making amyloid vanish Fatal systemic amyloidosis is caused by extracellular amyloid deposition that disrupts tissue structure and function. The normal plasma protein, serum amyloid P component (SAP), is always present within amyloid deposits. Richards et al. now show that previous depletion of circulating SAP by the drug, miridesap, uniquely enables subsequent administration of the humanized anti-SAP antibody, dezamizumab, to patients with systemic amyloidosis. Dezamizumab bound to residual SAP in the amyloid deposits and triggered their removal. Repeat cycles of miridesap followed by dezamizumab progressively removed amyloid from the liver, spleen, and kidneys of the patients. Evidence of clinical benefit suggests that this new approach has potential to improve management and outcome for patients with systemic amyloidosis. Systemic amyloidosis is a fatal disorder caused by pathological extracellular deposits of amyloid fibrils that are always coated with the normal plasma protein, serum amyloid P component (SAP). The small-molecule drug, miridesap, [(R)-1-[6-[(R)-2-carboxy-pyrrolidin-1-yl]-6-oxo-hexanoyl]pyrrolidine-2-carboxylic acid (CPHPC)] depletes circulating SAP but leaves some SAP in amyloid deposits. This residual SAP is a specific target for dezamizumab, a fully humanized monoclonal IgG1 anti-SAP antibody that triggers immunotherapeutic clearance of amyloid. We report the safety, pharmacokinetics, and dose-response effects of up to three cycles of miridesap followed by dezamizumab in 23 adult subjects with systemic amyloidosis (ClinicalTrials.gov identifier: NCT01777243). Amyloid load was measured scintigraphically by amyloid-specific radioligand binding of 123I-labeled SAP or of 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Organ extracellular volume was measured by equilibrium magnetic resonance imaging and liver stiffness by transient elastography. The treatment was well tolerated with the main adverse event being self-limiting early onset rashes after higher antibody doses related to whole body amyloid load. Progressive dose-related clearance of hepatic amyloid was associated with improved liver function tests. 123I-SAP scintigraphy confirmed amyloid removal from the spleen and kidneys. No adverse cardiac events attributable to the intervention occurred in the six subjects with cardiac amyloidosis. Amyloid load reduction by miridesap treatment followed by dezamizumab has the potential to improve management and outcome in systemic amyloidosis.

Late gadolinium enhancement in Brugada syndrome: A marker for subtle underlying cardiomyopathy?

BACKGROUNDnThere is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease.nnnOBJECTIVEnThe purpose of this study was to characterize patients with Brugada syndrome (BrS) using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE).nnnMETHODSnBrS was diagnosed according to international guidelines. Twenty-six percent of patients with BrS carried SCN5A mutations. CMR data from 78 patients with BrS were compared with 78 healthy controls (44 ± 15 vs 42 ± 14 years; P = .434; and 64% vs 64% male; P = 1).nnnRESULTSnRight ventricular (RV) ejection fraction was slightly lower (61 ± 8% vs 64 ± 5%; P = .004) and RV end-systolic volume slightly greater (31 ± 10 mL/m2 vs 28 ± 6 mL/m2; P = .038) in BrS compared with controls. These values remained within the normal range. LGE was demonstrated in 8% of patients with BrS (left ventricular midwall LGE in 5%) but not in controls (P = .028). In patients with BrS with midwall LGE there were no other features of cardiomyopathy at the time of CMR, but genetic testing and follow-up revealed a desmoplakin mutation in 1 patient and evolution of T-wave inversion throughout all precordial ECG leads in another. Neither patient fulfils diagnostic criteria for arrhythmogenic right ventricular cardiomyopathy.nnnCONCLUSIONnSome patients with BrS have left ventricular midwall LGE consistent with an underlying cardiomyopathic process. Even cases without LGE show greater RV volumes and reduced RV function. These findings lend further support to the presence of subtle structural abnormalities in BrS. The BrS pattern with LGE may serve as early markers for evolution of a cardiomyopathic phenotype over time. CMR is a potentially useful adjunct investigation in the clinical evaluation of BrS.

Provision of magnetic resonance imaging for patients with ‘MR-conditional’ cardiac implantable electronic devices: an unmet clinical need

AimsnIncreasing need for magnetic resonance imaging (MRI) has driven the development of MR-conditional cardiac implantable electronic devices (CIEDs; pacemakers and defibrillators); however, patients still report difficulties obtaining scans. We sought to establish current provision for MRI scanning of patients with CIEDs in England.nnnMethods and resultsnA survey was distributed to all hospitals in England with MRI, to assess current practice. Information requested included whether hospitals currently offer MRI to this patient group, the number and type of scans acquired, local safety considerations, complications experienced and perceived obstacles to service provision in those departments not currently offering it. Responses were received from 195 of 227 (86%) of hospitals surveyed. Although 98% of departments were aware of MR-conditional devices, only 46% (n = 89) currently offer MRI scans to patients with CIEDs; of these, 85% of departments perform ≤10 scans per year. No major complications were reported from MRI scanning in patients with MR-conditional devices. Current barriers to service expansion include perceived concerns regarding potential risk, lack of training, logistical difficulties, and lack of cardiology support.nnnConclusionnProvision of MRI for patients with CIEDs is currently poor, despite increasing numbers of patients with MR-conditional devices and extremely low reported complication rates.

Cardiac Structural and Functional Consequences of Amyloid Deposition by Cardiac Magnetic Resonance and Echocardiography and Their Prognostic Roles

OBJECTIVESnThis cross-sectional study aimed to describe the functional and structural cardiac abnormalities that occur across a spectrum of cardiac amyloidosis burden and to identify the strongest cardiac functional and structural prognostic predictors in amyloidosis using cardiac magnetic resonance (CMR) and echocardiography.nnnBACKGROUNDnCardiac involvement in light chain and transthyretin amyloidosis is the main driver of prognosis and influences treatment strategies. Numerous measures of cardiac structure and function are assessed by multiple imaging modalities in amyloidosis.nnnMETHODSnA total f 322 subjects (311 systemic amyloidosis and 11 transthyretin gene mutation carriers) underwent comprehensive CMR and transthoracic echocardiography. The probabilities of 11 commonly measured structural and functional cardiac parameters being abnormal with increasing cardiac amyloidosis burden were evaluated. Cardiac amyloidosis burden was quantified using CMR-derived extracellular volume. The prognostic capacities of these parameters to predict death in amyloidosis were assessed using Cox proportional hazards models.nnnRESULTSnLeft ventricular mass and mitral annular plane systolic excursion by CMR along with strain and E/e by echocardiography have high probabilities of being abnormal at low cardiac amyloid burden. Reductions in biventricular ejection fractions and elevations in biatrial areas occur at high burdens of infiltration. The probabilities of indexed stroke volume, myocardial contraction fraction, and tricuspid annular plane systolic excursion (TAPSE) being abnormal occur more gradually with increasing extracellular volume. Ninety patients (28%) died during a median follow-up of 22 months (interquartile range: 10 to 38 months). Univariable analysis showed that all imaging markers studied significantly predicted outcome. Multivariable analysis showed that TAPSE (hazard ratio: 1.46; 95% confidence interval: 1.16 to 1.85; pxa0< 0.01) and indexed stroke volume (hazard ratio: 1.24; 95% confidence interval: 1.04 to 1.48; pxa0< 0.05) by CMR were the only independent predictors of mortality.nnnCONCLUSIONSnSpecific functional and structural abnormalities characterize different burdens of cardiac amyloid deposition. In a multimodality imaging assessment of a large cohort of amyloidosis patients, CMR-derived TAPSE and indexed stroke volume are the strongest prognostic cardiac functional markers.

Prospective comparison of novel dark blood late gadolinium enhancement with conventional bright blood imaging for the detection of scar

BackgroundConventional bright blood late gadolinium enhancement (bright blood LGE) imaging is a routine cardiovascular magnetic resonance (CMR) technique offering excellent contrast between areas of LGE and normal myocardium. However, contrast between LGE and blood is frequently poor. Dark blood LGE (DB LGE) employs an inversion recovery T2 preparation to suppress the blood pool, thereby increasing the contrast between the endocardium and blood. The objective of this study is to compare the diagnostic utility of a novel DB phase sensitive inversion recovery (PSIR) LGE CMR sequence to standard bright blood PSIR LGE.MethodsOne hundred seventy-two patients referred for clinical CMR were scanned. A full left ventricle short axis stack was performed using both techniques, varying which was performed first in a 1:1 ratio. Two experienced observers analyzed all bright blood LGE and DB LGE stacks, which were randomized and anonymized. A scoring system was devised to quantify the presence and extent of gadolinium enhancement and the confidence with which the diagnosis could be made.ResultsA total of 2752 LV segments were analyzed. There was very good inter-observer correlation for quantifying LGE. DB LGE analysis found 41.5% more segments that exhibited hyperenhancement in comparison to bright blood LGE (248/2752 segments (9.0%) positive for LGE with bright blood; 351/2752 segments (12.8%) positive for LGE with DB; pu2009<u20090.05). DB LGE also allowed observers to be more confident when diagnosing LGE (bright blood LGE high confidence in 154/248 regions (62.1%); DB LGE in 275/324 (84.9%) regions (pu2009<u20090.05)). Eighteen patients with no bright blood LGE were found to have had DB LGE, 15 of whom had no known history of myocardial infarction.ConclusionsDB LGE significantly increases LGE detection compared to standard bright blood LGE. It also increases observer confidence, particularly for subendocardial LGE, which may have important clinical implications.

Invasive or non-invasive imaging for detecting high-risk coronary lesions?

ABSTRACT Introduction: Advances in our understanding about atherosclerotic evolution have enabled us to identify specific plaque characteristics that are associated with coronary plaque vulnerability and cardiovascular events. With constant improvements in signal and image processing an arsenal of invasive and non-invasive imaging modalities have been developed that are capable of identifying these features allowing in vivo assessment of plaque vulnerability. Areas covered: This review article presents the available and emerging imaging modalities introduced to assess plaque morphology and biology, describes the evidence from the first large scale studies that evaluated the efficacy of invasive and non-invasive imaging in detecting lesions that are likely to progress and cause cardiovascular events and discusses the potential implications of the in vivo assessment of coronary artery pathology in the clinical setting. Expert commentary: Invasive imaging, with its high resolution, and in particular hybrid intravascular imaging appears as the ideal approach to study the mechanisms regulating atherosclerotic disease progression; whereas non-invasive imaging is expected to enable complete assessment of coronary tree pathology, detection of high-risk lesions, more accurate risk stratification and thus to allow a personalized treatment of vulnerable patients.

Myocardial Fibrosis in Hypertensive Heart Failure : Does Quality Rather Than Quantity Matter?∗

“It is quality rather than quantity that matters.”—Lucius Annaeus Seneca [(1)][1]nnThe biology of heart failure is complex and diverse [(2)][2], posing challenges for developing efficacious therapies. All but one recent phase III heart failure trial failed to reduce mortality [(3)][3]. Unlike

Reproducibility of native T1 mapping using ShMOLLI and MOLLI - implications for sample size calculation

Background Native T1 mapping is becoming established to help diagnose and monitor myocardial disease. The reproducibility of T1 mapping has not been well characterized, despite the important implications both for interpreting serial clinical studies, and for sample size calculation for surrogate endpoint in clinical trials. The SCMR consensus statement recommends measuring T1 in 2 imaging views. We investigated the test-retest reproducibility of two native T1 mapping techniques using different imaging views.