Fractal analysis of left ventricular trabeculations is associated with impaired myocardial deformation in healthy Chinese

Background

Left ventricular (LV) non-compaction (LVNC) is defined by extreme LV trabeculation, but is measured variably. Here we examined the relationship between quantitative measurement in LV trabeculation and myocardial deformation in health and disease and determined the clinical utility of semi-automated assessment of LV trabeculations.

Methods

Cardiovascular magnetic resonance (CMR) was performed in 180 healthy Singaporean Chinese (age 20–69 years; males, n?=?91), using balanced steady state free precession cine imaging at 3T. The degree of LV trabeculation was assessed by fractal dimension (FD) as a robust measure of trabeculation complexity using a semi-automated technique. FD measures were determined in healthy men and women to derive normal reference ranges. Myocardial deformation was evaluated using feature tracking. We tested the utility of this algorithm and the normal ranges in 10 individuals with confirmed LVNC (non-compacted/compacted; NC/C ratio?>?2.3 and ≥1 risk factor for LVNC) and 13 individuals with suspected disease (NC/C ratio?>?2.3).

Results

Fractal analysis is a reproducible means of assessing LV trabeculation extent (intra-class correlation coefficient: intra-observer, 0.924, 95% CI [0.761–0.973]; inter-observer, 0.925, 95% CI [0.821–0.970]). The overall extent of LV trabeculation (global FD: 1.205?±?0.031) was independently associated with increased indexed LV end-diastolic volume and mass (sβ =?0.35; p?<?0.001 and sβ =?0.13; p?<?0.01, respectively) after adjusting for age, sex and body mass index. Increased LV trabeculation was independently associated with reduced global circumferential strain (sβ =?0.17, p?=?0.013) and global diastolic circumferential and radial strain rates (sβ =?0.25, p?<?0.001 and sβ =??0.15, p?=?0.049, respectively). Abnormally high FD was observed in all patients with a confirmed diagnosis of LVNC. Five out of 13 individuals with suspected LVNC had normal FD, despite NC/C?>?2.3.

Conclusion

This study defines the normal range of LV trabeculation in healthy Chinese that can be used to make or refute a diagnosis of LVNC using the fractal analysis tool, which we make freely available. We also show that increased myocardial trabeculation is associated with higher LV volumes, mass and reduced myocardial strain.

     

Incidence and predictors of left ventricular thrombus by cardiovascular magnetic resonance in acute ST-segment elevation myocardial infarction treated by primary percutaneous coronary intervention: a meta-analysis

Introduction

The incidence of left ventricular (LV) thrombus formation in ST-segment elevation myocardial infarction (STEMI) patients in the current era of primary percutaneous coronary intervention (PCI) is not well established. We performed a meta-analysis to assess the actual incidence and predictors of LV thrombus by cardiovascular magnetic resonance (CMR) in STEMI treated by primary PCI.

Methods

We searched MEDLINE and EMBASE databases up to February 2018. We included all studies published as a full-text article, reporting the incidence of LV thrombus by CMR within 1 month following acute STEMI in patients treated by primary PCI. A binary random-effects model was used to estimate the pooled incidence of LV thrombus. The diagnostic performance of transthoracic echocardiography (TTE) as compared with CMR was pooled to obtain the sensitivity and specificity of TTE with CMR as the gold standard. Embolic and bleeding complications of LV thrombus were also evaluated.

Results

Ten studies were included in the meta-analysis. The incidence of LV thrombus by CMR in all-comer STEMI patients (n?=?2072) was 6.3% with 96% of LV thrombus occurring in those with anterior STEMI (12.2% incidence). When only anterior STEMI with LVEF<?50% were considered (n?=?447), the incidence of LV thrombus was 19.2%. Compared with CMR, the sensitivity of TTE to detect LV thrombus was 29% with a specificity of 98%. The sensitivity of TTE increased to 70% in those with anterior STEMI and reduced LVEF. LV thrombus resolved in 88% of cases by 3 to 6 months. After 1–2 years follow-up, the embolic complication rate was similar at 1.5% (P?=?0.25) but the bleeding complication rate was significantly higher (8.8% versus 0.5%, P?<?0.001) in the LV thrombus group on triple therapy when compared to the no LV thrombus group on dual antiplatelet therapy.

Conclusion

In the primary PCI era, CMR detection of an LV thrombus post-STEMI remains high with incidence of nearly 20% in anterior STEMI with depressed LVEF. Patients with LV thrombus treated by triple therapy had similar embolic complications but higher bleeding complications than those with no LV thrombus treated with dual antiplatelet therapy. A 3 month follow-up CMR scan to guide anticoagulation duration might help mitigate bleeding risk.

     

Left ventricular synchrony,torsion, and recoil mechanics in Ebstein’s anomaly: insights from cardiovascular magnetic resonance

Background

Disease progression and heart failure development in Ebstein’s Anomaly (EA) of the tricuspid valve is characterized by both right and left ventricular (LV) deterioration. The mechanisms underlying LV dysfunction and their role in heart failure development are incompletely understood. We hypothesized that LV dyssynchrony and impaired torsion and recoil mechanics induced by paradoxical movement of the basal septum may play a role in heart failure development.

Methods

31 EA patients and 31 matched controls underwent prospective cardiovascular magnetic resonance (CMR). CMR feature tracking (CMR-FT) was performed on apical, midventricular and basal short-axis and 4D–volume analysis was performed using three long-axis views and a short axis cine stack employing dedicated software. Circumferential uniformity ratio estimates (CURE) time-to-peak-based circumferential systolic dyssynchrony index (C-SDI), 4D volume analysis derived SDI (4D–SDI), torsion (Tor) and systolic (sysTR) and diastolic torsion rate (diasTR) were calculated for the LV. QRS duration, brain natriuretic peptide, NYHA and Total R/L-Volume Index (R/L Index) were obtained.

Results

EA patients (31.5 years; controls 31.4 years) had significantly longer QRS duration (123.35 ms?±?26.36 vs. 97.33 ms ±?11.89 p <?0.01) and showed more LV dyssynchrony (4D–SDI 7.60%?±?4.58 vs. 2.54%?±?0.62, p <?0.001; CURE 0.77?±?0.05 vs. 0.86?±?0.03, p?<?0.001; C-SDI 7.70?±?3.38 vs. 3.80?±?0.91, p =?0.001). There were significant associations of LV dyssynchrony with heart failure parameters and QRS duration. Although torsion and recoil mechanics did not differ significantly (p >?0.05) there was an association of torsion and recoil mechanics with dyssynchrony parameters CURE (sysTR r =??0.426; p =?0.017, diasTR r =?0.419; p =?0.019), 4D–SDI (sysTR r =?0.383; p =?0.044) and C-SDI (diasTR r =??0.364; p?=?0.044).

Conclusions

EA is characterized by LV intra-ventricular dyssynchrony, which is associated with heart failure and disease severity parameters. Markers of dyssynchrony can easily be quantified from CMR-FT, and may have a role in the assessment of altered cardiac function, carrying potential management implications for EA patients.

     

Association between left ventricular mechanics and diffuse myocardial fibrosis in patients with repaired Tetralogy of Fallot: a cross-sectional study

Background

Patients with repaired tetralogy of Fallot (TOF) have progressive, adverse biventricular remodeling, leading to abnormal contractile mechanics. Defining the mechanisms underlying this dysfunction, such as diffuse myocardial fibrosis, may provide insights into poor long-term outcomes. We hypothesized that left ventricular (LV) diffuse fibrosis is related to impaired LV mechanics.

Methods

Patients with TOF were evaluated with cardiac magnetic resonance in which modified Look-Locker (MOLLI) T1-mapping and spiral cine Displacement encoding (DENSE) sequences were acquired at three LV short-axis positions. Linear mixed modeling was used to define the association between regional LV mechanics from DENSE based on regional T1-derived diffuse fibrosis measures, such as extracellular volume fraction (ECV).

Results

Forty patients (26?±?11 years) were included. LV ECV was generally within normal range (0.24?±?0.05). For LV mechanics, peak circumferential strains (?15?±?3%) and dyssynchrony indices (16?±?8 ms) were moderately impaired, while peak radial strains (29?±?8%) were generally normal. After adjusting for patient age, sex, and regional LV differences, ECV was associated with log-adjusted LV dyssynchrony index (β?=?0.67) and peak LV radial strain (β?=??0.36), but not LV circumferential strain. Moreover, post-contrast T1 was associated with log-adjusted LV diastolic circumferential strain rate (β?=?0.37).

Conclusions

We observed several moderate associations between measures of fibrosis and impaired mechanics, particularly the LV dyssynchrony index and peak radial strain. Diffuse fibrosis may therefore be a causal factor in some ventricular dysfunction in TOF.

     

Pivotal Bioequivalence Study of Clopacin<Superscript>®</Superscript>, a Generic Formulation of Clopidogrel 75 mg Film-Coated Tablets

Introduction

Clopacin^® (Acino Pharma AG) is a proprietary, besylate salt and lactose-free formulation of the widely-used anti-platelet treatment, clopidogrel. This study aimed to evaluate the bioequivalence of Clopacin^® with the originator as reference drug, using a guideline-compliant trial design: open-labeled, randomized, single-dose (clopidogrel 75 mg tablet), two-period, crossover trial in 48 healthy male volunteers, with a 7 day wash-out period.

Methods

Plasma samples were collected at intervals and extracted before quantifying clopidogrel concentrations using a fully validated LC–MS/MS method. Bioequivalence of Clopacin^® and the reference drug was established by comparison of the primary pharmacokinetic parameters, C _max, AUC_0–t, and AUC_0–∞.

Results

The parameter values were similar for the two products (analysis of variance) and provided Clopacin/reference ratios (least squares means) of >90% and 90% confidence intervals (CIs 84.64–105.50%, 90.43–111.22%, 88.75–110.71%, respectively) that were well within the limits set for defining bioequivalence, according to international guidelines. The respective Clopacin^® and reference drug values for mean time to maximal plasma clopidogrel concentration (t _max) were 0.83 and 0.91 h, and for terminal elimination half-life were 3.99 and 3.51 h. The intra-subject coefficients of variability for maximal plasma clopidogrel concentration (C _max), area under the plasma clopidogrel concentration versus time curve, at 48 h (AUC_0–t) and extrapolated to infinity (AUC_0–∞) were 32.2%, 30.2%, and 28.9% (least square means), respectively, and the respective power values were 99.5%, 97.1%, and 95.3%.

Conclusion

This bioequivalence study provided robust clopidogrel pharmacokinetic data that established the bioequivalence of Clopacin^® and the reference originator drug.

Funding

Acino Pharma AG (formerly Cimex AG)

     

Validation of a rapid semi-automated method to assess left atrial longitudinal phasic strains on cine cardiovascular magnetic resonance imaging

Background

Abnormal left atrial (LA) function is a marker of cardiac dysfunction and adverse cardiovascular outcome, but is difficult to assess, and hence not, routinely quantified. We aimed to determine the feasibility and effectiveness of a fast method to measure long-axis LA strain and strain rate (SR) with standard cardiovascular magnetic resonance (CMR) compared to conventional feature tracking (FT) derived longitudinal strain.

Methods

We studied 50 normal controls, 30 patients with hypertrophic cardiomyopathy, and 100 heart failure (HF) patients, including 40 with reduced ejection fraction (HFrEF), 30 mid-range ejection fraction (HFmrEF) and 30 preserved ejection fraction (HFpEF). LA longitudinal strain and SR parameters were derived by tracking the distance between the left atrioventricular junction and a user-defined point at the mid posterior LA wall on standard cine CMR two- and four-chamber views. LA performance was analyzed at three distinct cardiac phases: reservoir function (reservoir strain ε_s and strain rate SR_s), conduit function (conduit strain ε_e and strain rate SR_e) and booster pump function (booster strain ε_a and strain rate SR_a).

Results

There was good agreement between LA longitudinal strain and SR assessed using the fast and conventional FT-CMR approaches (r?=?0.89 to 0.99, p?<?0.001). The fast strain and SRs showed a better intra- and inter-observer reproducibility and a 55% reduction in evaluation time (85?±?10 vs. 190?±?12 s, p?<?0.001) compared to FT-CMR. Fast LA measurements in normal controls were 35.3?±?5.2% for ε_s, 18.1?±?4.3% for ε_e, 17.2?±?3.5% for ε_a, and 1.8?±?0.4, ??2.0?±?0.5, ??2.3?±?0.6 s^??1 for the respective phasic SRs. Significantly reduced LA strains and SRs were observed in all patient groups compared to normal controls. Patients with HFpEF and HFmrEF had significantly smaller ε_s, SR_s, ε_e and SR_e than hypertrophic cardiomyopathy, and HFmrEF had significantly impaired LA reservoir and booster function compared to HFpEF. The fast LA strains and SRs were similar to FT-CMR for discriminating patients from controls (area under the curve (AUC)?=?0.79 to 0.96 vs. 0.76 to 0.93, p?=?NS).

Conclusions

Novel quantitative LA strain and SR derived from conventional cine CMR images are fast assessable parameters for LA phasic function analysis.

     

Quantitative myocardial first-pass cardiovascular magnetic resonance perfusion imaging using hyperpolarized [1-<Superscript>13</Superscript>C] pyruvate

Background

The feasibility of absolute myocardial blood flow quantification and suitability of hyperpolarized [1-¹³C] pyruvate as contrast agent for first-pass cardiovascular magnetic resonance (CMR) perfusion measurements are investigated with simulations and demonstrated in vivo in a swine model.

Methods

A versatile simulation framework for hyperpolarized CMR subject to physical, physiological and technical constraints was developed and applied to investigate experimental conditions for accurate perfusion CMR with hyperpolarized [1-¹³C] pyruvate. Absolute and semi-quantitative perfusion indices were analyzed with respect to experimental parameter variations and different signal-to-noise ratio (SNR) levels. Absolute myocardial blood flow quantification was implemented with an iterative deconvolution approach based on Fermi functions. To demonstrate in vivo feasibility, velocity-selective excitation with an echo-planar imaging readout was used to acquire dynamic myocardial stress perfusion images in four healthy swine. Arterial input functions were extracted from an additional image slice with conventional excitation that was acquired within the same heartbeat.

Results

Simulations suggest that obtainable SNR and B₀ inhomogeneity in vivo are sufficient for the determination of absolute and semi-quantitative perfusion with ≤25% error. It is shown that for expected metabolic conversion rates, metabolic conversion of pyruvate can be neglected over the short duration of acquisition in first-pass perfusion CMR. In vivo measurements suggest that absolute myocardial blood flow quantification using hyperpolarized [1-¹³C] pyruvate is feasible with an intra-myocardial variability comparable to semi-quantitative perfusion indices.

Conclusion

The feasibility of quantitative hyperpolarized first-pass perfusion CMR using [1-¹³C] pyruvate has been investigated in simulations and demonstrated in swine. Using an approved and metabolically active compound is envisioned to increase the value of hyperpolarized perfusion CMR in patients.

     

Cardiovascular magnetic resonance left ventricular strain in end-stage renal disease patients after kidney transplantation

Background

Cardiovascular disease is a significant cause of morbidity and mortality in patients with end-stage renal disease (ESRD) and kidney transplant (KT) patients. Compared with left ventricular (LV) ejection fraction (LVEF), LV strain has emerged as an important marker of LV function as it is less load dependent. We sought to evaluate changes in LV strain using cardiovascular magnetic resonance imaging (CMR) in ESRD patients who received KT, to determine whether KT may improve LV function.

Methods

We conducted a prospective multi-centre longitudinal study of 79 ESRD patients (40 on dialysis, 39 underwent KT). CMR was performed at baseline and at 12?months after KT.

Results

Among 79 participants (mean age 55 years; 30% women), KT patients had significant improvement in global circumferential strain (GCS) (p?=?0.007) and global radial strain (GRS) (p?=?0.003), but a decline in global longitudinal strain (GLS) over 12?months (p?=?0.026), while no significant change in any LV strain was observed in the ongoing dialysis group. For KT patients, the improvement in LV strain paralleled improvement in LVEF (57.4?±?6.4% at baseline, 60.6%?±?6.9% at 12?months; p?=?0.001). For entire cohort, over 12?months, change in LVEF was significantly correlated with change in GCS (Spearman’s r?=???0.42, p?<?0.001), GRS (Spearman’s r?=?0.64, p?<?0.001), and GLS (Spearman’s r?=???0.34, p?=?0.002). Improvements in GCS and GRS over 12?months were significantly correlated with reductions in LV end-diastolic volume index and LV end-systolic volume index (all p?<?0.05), but not with change in blood pressure (all p?>?0.10).

Conclusions

Compared with continuation of dialysis, KT was associated with significant improvements in LV strain metrics of GCS and GRS after 12?months, which did not correlate with blood pressure change. This supports the notion that KT has favorable effects on LV function beyond volume and blood pessure control. Larger studies with longer follow-up are needed to confirm these findings.

     

Optimized CEST cardiovascular magnetic resonance for assessment of metabolic activity in the heart

Background

Previous studies have linked cardiac dysfunction to loss of metabolites in the creatine kinase system. Chemical exchange saturation transfer (CEST) is a promising metabolic cardiovascular magnetic resonance (CMR) imaging technique and has been applied in the heart for creatine mapping. However, current limitations include: (a) long scan time, (b) residual cardiac and respiratory motion, and (c) B₀ field variations induced by respiratory motion. An improved CEST CMR technique was developed to address these problems.

Methods

Animals with chronic myocardial infarction (N?=?15) were scanned using the proposed CEST CMR technique and a late gadolinium enhancement (LGE)  sequence as reference. The major improvements of the CEST CMR technique are: (a) Images were acquired by single-shot FLASH, significantly increasing the scan efficiency. (b) All images were registered to reduce the residual motion. (c) The acquired Z-spectrum was analyzed using 3-pool-model Lorentzian-line fitting to generate CEST signal, reducing the impact of B₀ field shifting due to respiratory motion. Feasibility of the technique was tested in a porcine model with chronic myocardial infarction. CEST signal was measured in the scar, border zone and remote myocardium. Initial studies were performed in one patient.

Results

In all animals, healthy remote myocardial CEST signal was elevated (0.16?±?0.02) compared to infarct CEST signal (0.09?±?0.02, P?<?0.001) and the border zone (0.12?±?0.02, P?<?0.001). For both animal and patient studies, the hypointense regions in the CEST contrast maps closely match the bright areas in the LGE images.

Conclusions

The proposed CEST CMR technique was developed to address long scan times, respiratory and cardiac motion, and B₀ field variations. Lower CEST signal in bright region of the LGE image is consistent with the fact that myocardial infarction has reduced metabolic activity.

     

Maldistribution of pulmonary blood flow in patients after the Fontan operation is associated with worse exercise capacity

Background

Maldistribution of pulmonary artery blood flow (MPBF) is a potential complication in patients who have undergone single ventricle palliation culminating in the Fontan procedure. Cardiovascular magnetic resonance (CMR) is the best modality that can evaluate MPBF in this population. The purpose of this study is to identify the prevalence and associations of MPBF and to determine the impact of MPBF on exercise capacity after the Fontan operation.

Methods

This retrospective single-center study included all patients after Fontan operation who had maximal cardiopulmonary exercise test (CPET) and CMR with flow measurements of the branch pulmonary arteries. MPBF was defined as >?20% difference in branch pulmonary artery flow. Exercise capacity was measured as percent of predicted oxygen consumption at peak exercise (% predicted VO₂). Linear and logistic regression models were used to determine univariate and multivariable predictors of exercise capacity and correlates of MPBF, respectively.

Results

A total of 147 patients who had CMR between 1999 and 2017 were included (median age at CMR 21.8?years [interquartile range (IQR) 16.5–30.6]) and the median time between CMR and CPET was 2.8?months [IQR 0–13.8]. Fifty-three patients (36%) had MPBF (95% CI 29–45%). The mean % predicted VO₂ was 63?±?16%. Patients with MPBF had lower mean % predicted VO₂ compared to patients without MPBF (60?±?14% versus 65?±?16%, p?=?0.04). On multivariable analysis, a lower % predicted VO₂ was independently associated with longer time since Fontan, higher ventricular mass-to-volume ratio, and MPBF. On multivariable analysis, only compression of the branch pulmonary arteries by the ascending aorta or aortic root was associated with MPBF (OR 6.5, 95% CI 5.6–7.4, p?<?0.001).

Conclusion

In patients after the Fontan operation, MPBF is common and is independently associated with lower exercise capacity. MPBF was most likely to be caused by pulmonary artery compression by the aortic root or the ascending aorta. This study identifies MPBF as an important risk factor and as a potential target for therapeutic interventions in this fragile patient population.

     

Quantification of mitral regurgitation in patients with hypertrophic cardiomyopathy using aortic and pulmonary flow data: impacts of left ventricular outflow tract obstruction and different left ventricular segmentation methods

Background

Cardiovascular magnetic resonance (CMR) imaging in patients with hypertrophic cardiomyopathy (HCM) enables the assessment of not only left ventricular (LV) hypertrophy and scarring but also the severity of mitral regurgitation. CMR assessment of mitral regurgitation is primarily based on the difference between LV stroke volume (LVSV) and aortic forward flow (Ao) measured using the phase-contrast (PC) technique. However, LV outflow tract (LVOT) obstruction causing turbulent, non-laminar flow in the ascending aorta may impact the accuracy of aortic flow quantification, leading to false conclusions regarding mitral regurgitation severity. Thus, we decided to quantify mitral regurgitation in patients with HCM using Ao or, alternatively, main pulmonary artery forward flow (MPA) for mitral regurgitation volume (MRvol) calculations.

Methods

The analysis included 143 prospectively recruited subjects with HCM and 15 controls. MRvol was calculated as the difference between LVSV computed with either the inclusion (LVSV_incl) or exclusion (LVSV_excl) of papillary muscles and trabeculations from the blood pool and either Ao (MRvol_Aoi or MRvol_Aoe) or MPA (MRvol_MPAi or MRvol_MPAe). The presence or absence of LVOT obstruction was determined based on Doppler echocardiography findings.

Results

MRvol_Aoi was higher than MRvol_MPAi in HCM patients with LVOT obstruction [47.0 ml, interquartile range (IQR)?=?31.5–60.0 vs. 35.5 ml, IQR?=?26.0–51.0; p <?0.0001] but not in non-obstructive HCM patients (23.0 ml, IQR?=?16.0–32.0 vs. 24.0 ml, IQR?=?15.3–32.0; p?=?0.26) or controls (18.0 ml, IQR?=?14.3–21.8 vs. 20.0 ml, IQR?=?14.3–22.0; p?=?0.89). In contrast to controls and HCM patients without LVOT obstruction, in HCM patients with LVOT obstruction, aortic flow-based MRvol (MRvol_Aoi) was higher than pulmonary-based findings (MRvol_MPAi) (bias?=?9.5 ml; limits of agreement: ?11.7–30.7 with a difference of 47 ml in the extreme case). The differences between aortic-based and pulmonary-based MRvol values calculated using LVSV_excl mirrored those derived using LVSV_incl. However, MRvol values calculated using LVSV_excl were lower in all the groups analyzed (HCM with LVOT obstruction, HCM without LVOT obstruction, and controls) and with all methods of MRvol quantification used (p?≤?0.0001 for all comparisons).

Conclusions

In HCM patients, LVOT obstruction significantly affects the estimation of aortic flow, leading to its underestimation and, consequently, to higher MRvol values than those obtained with MPA-based MRvol calculations.

     

Left Atrial structure and function in hypertrophic cardiomyopathy sarcomere mutation carriers with and without left ventricular hypertrophy

Background

Impaired left atrial (LA) function is an early marker of cardiac dysfunction and predictor of adverse cardiac events. Herein, we assess LA structure and function in hypertrophy in hypertrophic cardiomyopathy (HCM) sarcomere mutation carriers with and without left ventricular hypertrophy (LVH).

Method

Seventy-three participants of the HCMNet study who underwent cardiovascular magnetic resonance (CMR) imaging were studied, including mutation carriers with overt HCM (n =?34), preclinical mutation carriers without HCM (n =?24) and healthy, familial controls (n =?15).

Results

LA volumes were similar between preclinical, control and overt HCM cohorts after covariate adjustment. However, there was evidence of impaired LA function with decreased LA total emptying function in both preclinical (64?±?8%) and overt HCM (59?±?10%), compared with controls (70?±?7%; p =?0.002 and p =?0.005, respectively). LA passive emptying function was also decreased in overt HCM (35?±?11%) compared with controls (47?±?10%; p =?0.006). Both LAtotal emptying function and LA passive emptying function were inversely correlated with the extent of late gadolinium enhancement (LGE; p?=?0.005 and p <?0.05, respectively), LV mass (p =?0.02 and p <?0.001) and interventricular septal thickness (p?<?0.001 for both) and serum NT-proBNP levels (p?<?0.001 for both).

Conclusion

LA dysfunction is detectable by CMR in preclinical HCM mutation carriers despite non-distinguishable LV wall thickness and LA volume. LA function appears most impaired in subjects with overt HCM and a greater extent of LV fibrosis.

     

Chagas’ Disease: Update on Current Diagnosis

Purpose of Review

Chagas’ disease has become an emerging health problem due to increased migration. In the present review, we have summarized the usefulness of non-invasive imaging tools for the diagnosis of cardiac involvement in Chagas’ disease, with emphasis on modern technologies. M-mode, bidimensional (2-D), and three-dimensional (3-D) echocardiographies may allow the evaluation of left ventricular (LV) regional and global contractile function, right ventricle (RV) impairment, evidence of aneurysms and thrombi, and assessment of diastolic function in any stage of the disease.

Recent Findings

New modalities such as strain and speckle-tracking imaging have brought non-invasive indices to the understanding of the mechanisms of cardiac dyssynchrony. The assessment of cardiac autonomic denervation using ¹²³I-metaiodobenzylguanidine (¹²³I-MIBG), LV, and RV systolic function and the study of LV mechanical dyssynchrony by gated cardiac blood pool are available in current nuclear imaging for patients with Chagas’ disease. The findings of myocardial fibrosis by cardiac magnetic resonance (CMR), mainly in inferolateral regions, are a marker of subclinical involvement and worse prognosis in Chagas’ disease, even in patients with preserved ventricular function.

Summary

The detection and quantification of early signs of heart involvement by new technologies should be useful for risk stratification and in the clinical decision process for new therapeutic methods and could improve the natural history of the disease.

     

Effectiveness and Persistence of Liraglutide Treatment Among Patients with Type 2 Diabetes Treated in Primary Care and Specialist Settings: A Subgroup Analysis from the EVIDENCE Study,a Prospective, 2-Year Follow-up,Observational, Post-Marketing Study

Introduction

The objective of this subgroup analysis is to investigate the effectiveness of liraglutide in people with type 2 diabetes (T2D) treated within the primary care physician (PCP) and specialist care settings.

Methods

EVIDENCE is a prospective, observational study of 3152 adults with T2D recently starting or about to start liraglutide treatment in France. We followed patients in the PCP and specialist settings for 2 years to evaluate the effectiveness of liraglutide in glycemic control and body weight reduction. Furthermore, we evaluated the changes in combined antihyperglycemic treatments, the reasons for prescribing liraglutide, patient satisfaction, and safety of liraglutide in these two treatment settings.

Results

After 2 years of follow-up, 477 out of 1209 (39.0%) of PCP and 297 out of 1398 (21.2%) of specialist-treated patients still used liraglutide and maintained the glycated hemoglobin (HbA_1c) target of <7.0%. Significant reductions from baseline were observed in both PCP- and specialist-treated cohorts in mean HbA_1c (?1.22% and ?0.8%, respectively), fasting plasma glucose (FPG) concentration (?39 and ?23 mg/dL), body weight (?4.4 and ?3.8 kg), and body mass index (BMI) (?1.5 and ?1.4 kg/m²), all p < 0.0001. Reductions in HbA_1c and FPG were significantly greater among PCP- compared with specialist-treated patients, p < 0.0001 for both. Patient treatment satisfaction was also significantly increased in both cohorts. Reported gastrointestinal adverse events were less frequent among PCP-treated patients compared with specialist-treated patients (4.5% vs. 16.1%).

Conclusion

Despite differences in demography and clinical characteristics of patients treated for T2D in PCP and specialty care, greater reduction in HbA_1c and increased glycemic control durability were observed with liraglutide in primary care, compared with specialist care. These data suggest that liraglutide treatment could benefit patients in primary care by delaying the need for further treatment intensification.

Trial Registration

ClinicalTrials.gov identifier, NCT01226966.

Funding

Novo Nordisk A/S.

     

Effects of caffeine on the detection of ischemia in patients undergoing adenosine stress cardiovascular magnetic resonance imaging

Background

Adenosine stress cardiovascular magnetic resonance (CMR) can detect significant coronary artery stenoses with high diagnostic accuracy. Caffeine is a nonselective competitive inhibitor of adenosine2A-receptors, which might hamper the vasodilator effect of adenosine stress, potentially yielding false-negative results. Much controversy exists about the influence of caffeine on adenosine myocardial perfusion imaging. Our study sought to investigate the effects of caffeine on ischemia detection in patients with suspected or known coronary artery disease (CAD) undergoing adenosine stress CMR.

Methods

Thirty patients with evidence of myocardial ischemia on caffeine-naïve adenosine stress CMR were prospectively enrolled and underwent repeat adenosine stress CMR after intake of 200 mg caffeine. Both CMR exams were then compared for evaluation of ischemic burden.

Results

Despite intake of caffeine, no conversion of a positive to a negative stress study occurred on a per patient basis. Although we found significant lower ischemic burden in CMR exams with caffeine compared to caffeine-naïve CMR exams, absolute differences varied only slightly (1 segment based on a 16-segment model, 3 segments on a 60-segment model, and 1 ml in total ischemic myocardial volume, p?<?0.001 each). Moreover, no relevant ischemia (≥2 segments in a 16-segment model) was missed by prior ingestion of caffeine.

Conclusions

Although differences were small and no relevant myocardial ischemia had been missed, prior consumption of caffeine led to significant reduction of ischemic burden, and might lower the high diagnostic and prognostic value of adenosine stress CMR. Therefore, we suggest that patients should still refrain from caffeine prior adenosine stress CMR tests.

     

Real-time assessment of right and left ventricular volumes and function in children using high spatiotemporal resolution spiral bSSFP with compressed sensing

Background

Real-time cardiovascular magnetic resonance (CMR) assessment of ventricular volumes and function enables data acquisition during free-breathing. The requirement for high spatiotemporal resolution in children necessitates the use of highly accelerated imaging techniques.

Methods

A novel real-time balanced steady state free precession (bSSFP) spiral sequence reconstructed using Compressed Sensing (CS) was prospectively validated against the breath-hold clinical standard for assessment of ventricular volumes in 60 children with congenital heart disease. Qualitative image scoring, quantitative image quality, as well as evaluation of biventricular volumes was performed. Standard BH and real-time measures were compared using the paired t-test and agreement for volumetric measures were evaluated using Bland Altman analysis.

Results

Acquisition time for the entire short axis stack (~?13 slices) using the spiral real-time technique was ~?20 s, compared to ~?348 s for the standard breath hold technique. Qualitative scores reflected more residual aliasing artefact (p?<?0.001) and lower edge definition (p?<?0.001) in spiral real-time images than standard breath hold images, with lower quantitative edge sharpness and estimates of image contrast (p?<?0.001).There was a small but statistically significant (p?<?0.05) overestimation of left ventricular (LV) end-systolic volume (1.0?±?3.5 mL), and underestimation of LV end-diastolic volume (??1.7?±?4.6 mL), LV stroke volume (??2.6?±?4.8 mL) and LV ejection fraction (??1.5?±?3.0%) using the real-time technique. We also observed a small underestimation of right ventricular stroke volume (??1.8?±?4.9 mL) and ejection fraction (??1.4?±?3.7%) using the real-time imaging technique. No difference in inter-observer or intra-observer variability were observed between the BH and real-time sequences.

Conclusions

Real-time bSSFP imaging using spiral trajectories combined with a compressed sensing reconstruction showed good agreement for quantification of biventricular metrics in children with heart disease, despite slightly lower image quality. This technique holds the potential for free breathing data acquisition, with significantly shorter scan times in children.

     

Characterizing Cardiac Involvement in Chronic Kidney Disease Using CMR—a Systematic Review

Purpose of Review

The aim of the review was to identify and describe recent advances (over the last 3 years) in cardiac magnetic resonance (CMR) imaging in patients with chronic kidney disease (CKD). We conducted a literature review in line with current guidelines.

Recent Findings

The authors identified 22 studies. Patients with CKD had left ventricular global and regional dysfunction and adverse remodeling. Stress testing with CMR revealed a reduced stress-response in CKD patients. Native T1 relaxation times (as a surrogate markers of fibrosis) are elevated in CKD patients, proportional to disease duration. Patients with CKD have reduced strain magnitudes and reduced aortic distensibility.

Summary

CMR has diagnostic utility to identify and characterize cardiac involvement in this patient group. A number of papers have described novel findings over the last 3 years, suggesting that CMR has potential to become more widely used in studies in this patient group.

     

Effects of adenosine and regadenoson on hemodynamics measured using cardiovascular magnetic resonance imaging

Background

Adenosine or regadenoson vasodilator stress cardiovascular magnetic resonance (CMR) is an effective non-invasive strategy for evaluating symptomatic coronary artery disease. Vasodilator injection typically precedes ventricular functional sequences to efficiently reduce overall scanning times, though the effects of vasodilators on CMR-derived ventricular volumes and function are unknown.

Methods

We prospectively enrolled 25 healthy subjects to undergo consecutive adenosine and regadenoson administration. Short axis CINE datasets were obtained on a 1.5 T scanner following adenosine (140mcg/kg/min IV for 6 min) and regadenoson (0.4 mg IV over 10 s) at baseline, immediately following administration, at 5 min intervals up to 15 min. Hemodynamic response, bi-ventricular volumes and ejection fractions were determined at each time point.

Results

Peak heart rate was observed early following administration of both adenosine and regadenoson. Heart rate returned to baseline by 10 min post-adenosine while remaining elevated at 15 min post-regadenoson (p?=?0.0015). Left ventricular (LV) ejection fraction (LVEF) increased immediately following both vasodilators (p?<?0.0001 for both) and returned to baseline following adenosine by 10 min (p?=?0.8397). Conversely, LVEF following regadenoson remained increased at 10 min (p?=?0.003) and 15 min (p?=?0.0015) with a mean LVEF increase at 15 min of 4.2?±?1.3%. Regadenoson resulted in a similar magnitude reduction in both LV end-diastolic volume index (LVEDVi) and LV end-systolic volume index (LVESVi) at 15 min whereas LVESVi resolved at 15 min following adenosine and LVEDVi remained below baseline values (p?=?0.52).

Conclusions

Regadenoson and adenosine have significant and prolonged impact on ventricular volumes and LVEF. In patients undergoing vasodilator stress CMR where ventricular volumes and LVEF are critical components to patient care, ventricular functional sequences should be performed prior to vasodilator use or consider the use of aminophylline in the setting of regadenoson. Additionally, heart rate resolution itself is not an effective surrogate for return of ventricular volumes and LVEF to baseline.

     

Feasibility of 3D black-blood variable refocusing angle fast spin echo cardiovascular magnetic resonance for visualization of the whole heart and great vessels in congenital heart disease

Background

Volumetric black-blood cardiovascular magnetic resonance (CMR) has been hampered by long scan times and flow sensitivity. The purpose of this study was to assess the feasibility of black-blood, electrocardiogram (ECG)-triggered and respiratory-navigated 3D fast spin echo (3D FSE) for the visualization of the whole heart and great vessels.

Methods

The implemented 3D FSE technique used slice-selective excitation and non-selective refocusing pulses with variable flip angles to achieve constant echo signal for tissue with T1 (880?ms) and T2 (40?ms) similar to the vessel wall. Ten healthy subjects and 21 patients with congenital heart disease (CHD) underwent 3D FSE and conventional 3D balanced steady-state free precession (bSSFP). The sequences were compared in terms of ability to perform segmental assessment, local signal-to-noise ratio (SNR_l) and local contrast-to-noise ratio (CNR_l).

Results

In both healthy subjects and patients with CHD, 3D FSE showed superior pulmonary vein but inferior coronary artery origin visualisation compared to 3D bSFFP. However, in patients with CHD the combination of 3D bSSFP and 3D FSE whole-heart imaging improves the success rate of cardiac morphological diagnosis to 100% compared to either technique in isolation (3D FSE, 23.8% success rate, 3D bSSFP, 5% success rate). In the healthy subjects SNR_l for 3D bSSFP was greater than for 3D FSE (30.1?±?7.3 vs 20.9?±?5.3; P?=?0.002) whereas the CNR_l was comparable (17.3?±?5.6 vs 17.4?±?4.9; P?=?0.91) between the two scans.

Conclusions

The feasibility of 3D FSE for whole-heart black-blood CMR imaging has been demonstrated. Due to their high success rate for segmental assessment, the combination of 3D bSSFP and 3D FSE may be an attractive alternative to gadolinium contrast enhanced morphological CMR in patients with CHD.

     

The relative atrial volume ratio and late gadolinium enhancement provide additive information to differentiate constrictive pericarditis from restrictive cardiomyopathy

Background

The differentiation of constrictive pericarditis (CP) from restrictive cariomyopathy (RCM) is often difficult. This study sought to determine the clinical utility of cardiovascular magnetic resonance imaging (CMR) for differentiating both these disorders.

Methods

Twenty-three patients with surgically documented CP, 22 patients with RCM and 25 normal subjects were included in the study. CMR yielded information about cardiac morphology, function and tissue characteristics. The left (LA) and right atrial (RA) volume was calculated using the area-length method. The relative atrial volume ratio (RAR) was defined as the LA volume divided by RA volume. Receiver operating characteristic curve analysis was used to test the ability of different variables in differentiating CP from RCM.

Results

The maximal pericardial thickness in CP patients was significantly larger than in normal subjects and RCM patients. The RA volume index in RCM patients (90.5 ± 35.3 mL/m²) was significantly larger than in CP patients (71.4 ± 15.7 mL/m², p = 0.006) and normal subjects (38.1 ± 9.0 mL/m², p < 0.001). The LA volume index in RCM (96.0 ± 37.0 mL/m²) and CP patients (105.6 ± 25.1 mL/m²) was significantly larger than in normal subjects (39.5 ± 9.5 mL/m², p < 0.001 for all). The RAR in CP patients (1.50 ± 0.29) was significantly larger than in RCM patients (1.12 ± 0.33, p < 0.001) and normal subjects (1.06 ± 0.20, p < 0.001). There were no differences between RCM patients and normal subjects in the RAR (p = 0.452). At a cut-off value of 1.32 for the RAR, the sensitivity was 82.6%, and the specificity was 86.4% in the detection of CP. Septal bounce was identified in 95.7% CP patients, in none of RCM patients and normal subjects. Late gadolinium enhancement (LGE) was present in 31.8% RCM patients and absence in all CP patients and normal subjects.

Conclusions

CMR with LGE and RAR can facilitate differentiation of CP from RCM.