Adelina Doltra

T1-Mapping and Outcome in Nonischemic Cardiomyopathy: All-Cause Mortality and Heart Failure

OBJECTIVES The study sought to examine prognostic relevance of T1 mapping parameters (based on a T1 mapping method) in nonischemic dilated cardiomyopathy (NIDCM) and compare them with conventional markers of adverse outcome. BACKGROUND NIDCM is a recognized cause of poor clinical outcome. NIDCM is characterized by intrinsic myocardial remodeling due to complex pathophysiological processes affecting myocardium diffusely. Lack of accurate and noninvasive characterization of diffuse myocardial disease limits recognition of early cardiomyopathy and effective clinical management in NIDCM. Cardiac magnetic resonance (CMR) supports detection of diffuse myocardial disease by T1 mapping. METHODS This is a prospective observational multicenter longitudinal study in 637 consecutive patients with dilated NIDCM (mean age 50 years [interquartile range: 37 to 76 years]; 395 males [62%]) undergoing CMR with T1 mapping and late gadolinium enhancement (LGE) at 1.5-T and 3.0-T. The primary endpoint was all-cause mortality. A composite of heart failure (HF) mortality and hospitalization was a secondary endpoint. RESULTS During a median follow-up period of 22 months (interquartile range: 19 to 25 months), we observed a total of 28 deaths (22 cardiac) and 68 composite HF events. T1 mapping indices (native T1 and extracellular volume fraction), as well as the presence and extent of LGE, were predictive of all-cause mortality and HF endpoint (p < 0.001 for all). In multivariable analyses, native T1 was the sole independent predictor of all-cause and HF composite endpoints (hazard ratio: 1.1; 95% confidence interval: 1.06 to 1.15; hazard ratio: 1.1; 95% confidence interval: 1.05 to 1.1; p < 0.001 for both), followed by the models including the extent of LGE and right ventricular ejection fraction, respectively. CONCLUSIONS Noninvasive measures of diffuse myocardial disease by T1 mapping are significantly predictive of all-cause mortality and HF events in NIDCM. We provide a basis for a novel algorithm of risk stratification in NIDCM using a complementary assessment of diffuse and regional disease by T1 mapping and LGE, respectively.

Temporal diffeomorphic free-form deformation: Application to motion and strain estimation from 3D echocardiography

This paper presents a new registration algorithm, called Temporal Diffeomorphic Free Form Deformation (TDFFD), and its application to motion and strain quantification from a sequence of 3D ultrasound (US) images. The originality of our approach resides in enforcing time consistency by representing the 4D velocity field as the sum of continuous spatiotemporal B-Spline kernels. The spatiotemporal displacement field is then recovered through forward Eulerian integration of the non-stationary velocity field. The strain tensor is computed locally using the spatial derivatives of the reconstructed displacement field. The energy functional considered in this paper weighs two terms: the image similarity and a regularization term. The image similarity metric is the sum of squared differences between the intensities of each frame and a reference one. Any frame in the sequence can be chosen as reference. The regularization term is based on the incompressibility of myocardial tissue. TDFFD was compared to pairwise 3D FFD and 3D+t FFD, both on displacement and velocity fields, on a set of synthetic 3D US images with different noise levels. TDFFD showed increased robustness to noise compared to these two state-of-the-art algorithms. TDFFD also proved to be more resistant to a reduced temporal resolution when decimating this synthetic sequence. Finally, this synthetic dataset was used to determine optimal settings of the TDFFD algorithm. Subsequently, TDFFD was applied to a database of cardiac 3D US images of the left ventricle acquired from 9 healthy volunteers and 13 patients treated by Cardiac Resynchronization Therapy (CRT). On healthy cases, uniform strain patterns were observed over all myocardial segments, as physiologically expected. On all CRT patients, the improvement in synchrony of regional longitudinal strain correlated with CRT clinical outcome as quantified by the reduction of end-systolic left ventricular volume at follow-up (6 and 12months), showing the potential of the proposed algorithm for the assessment of CRT.

Autologous CD133+ bone marrow cells and bypass grafting for regeneration of ischaemic myocardium: the Cardio133 trial

AIMS Intra-myocardial transplantation of CD133(+) bone marrow stem cells (BMC) yielded promising results in clinical pilot trials. We now performed the double-blinded, randomized, placebo-controlled CARDIO133 trial to determine its impact on left ventricular (LV) function and clinical symptoms. METHODS AND RESULTS Sixty patients with chronic ischaemic heart disease and impaired LV function (left ventricular ejection fraction, LVEF <35%) were randomized to undergo either coronary artery bypass grafting (CABG) and injection of CD133(+) BMC in the non-transmural, hypokinetic infarct border zone (CD133), or CABG and placebo injection (placebo). Pre-operative LVEF was 27 ± 6% in CD133 patients and 26 ± 6% in placebo patients. Outcome was assessed after 6 months, and the primary endpoint was LVEF measured by cardiac magnetic resonance imaging (MRI) at rest. The incidence of adverse events was similar in both groups. There was no difference in 6-min walking distance, Minnesota Living with Heart Failure score, or Canadian Cardiovascular Society (CCS) class between groups at follow-up, and New York Heart Association class improved more in the placebo group (P = 0.004). By cardiac MRI, LVEF at 6 months was 33 ± 8% in the placebo group and 31 ± 7% in verum patients (P = 0.3), with an average inter-group difference of -2.1% (95% CI -6.3 to 2.1). Systolic or diastolic LV dimensions at 6 months were not different, either. In the CD133 group, myocardial perfusion at rest recovered in more LV segments than in the placebo group (9 vs. 2%, P < 0.001). Scar mass decreased by 2.2 ± 5 g in CD133(+) patients (P = 0.05), but was unchanged in the placebo group (0.3 ± 4 g, P = 0.7; inter-group difference in change = 2 g (95% CI -1.1 to 5)). By speckle-tracking echocardiography, cell-treated patients showed a better recovery of regional wall motion when the target area was posterior. CONCLUSION Although there may be some improvements in scar size and regional perfusion, intra-myocardial injection of CD133(+) BMC has no effect on global LV function and clinical symptoms. Improvements in regional myocardial function are only detectable in patients with posterior infarction, probably because the interventricular septum after anterior infarction is not accessible by trans-epicardial injection. CLINICAL TRIAL REGISTRATION This trial was registered at http://www.clinicaltrials.gov under NCT00462774.

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. 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 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. Conclusions— 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 spatiotemporal statistical atlas of motion for the quantification of abnormal myocardial tissue velocities

In this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT candidates with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT.

EAARN score, a predictive score for mortality in patients receiving cardiac resynchronization therapy based on pre‐implantation risk factors

The beneficial effects of CRT in patients with advanced heart failure, wide QRS, and low LVEF have been clearly established. Nevertheless, mortality remains high in some patients. The aims of our study were to identify the predictors of mortality in patients treated with CRT and to design a risk score for mortality.

Emerging Concepts for Myocardial Late Gadolinium Enhancement MRI

Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments.

Potential Reduction of Interstitial Myocardial Fibrosis With Renal Denervation

Background Hypertensive cardiomyopathy is characterized by myocyte hypertrophy and interstitial fibrosis. The effects of renal denervation (RD) on the heart are poorly understood. New magnetic resonance imaging techniques (extracellular volume fraction) permit the quantitative assessment of myocardial fibrosis. Our aim was to study the effects of RD on myocardial fibrosis. Methods and Results Twenty‐three patients with resistant hypertension undergoing RD and 5 resistant hypertensive controls were prospectively included. Cardiac magnetic resonance imaging at 1.5 T was performed before RD and at 6‐month follow‐up. Indexed left ventricular mass, septal extracellular volume fraction, and indexed absolute extracellular volume (a quantitative measure of extracellular matrix) were quantified. All data are reported as mean±SD deviation (median). Decreases in systolic (161.96±19.09 [160] versus 144.78±16.48 [143] mm Hg, P<0.0001) and diastolic (85.61±12.88 [83] versus 80.39±11.93 [81] mm Hg, P=0.018) blood pressures and in indexed left ventricular mass (41.83±10.20 [41.59] versus 37.72±7.44 [38.49] g/m1.7, P=0.001) were observed at follow‐up only in RD patients. No significant differences in extracellular volume were found (26.24±3.92% [26.06%] versus 25.74±4.53% [25.63%], P=0.605). A significant decrease in absolute extracellular volume was observed after 6 months in RD patients exclusively (10.36±2.25 [10.79] versus 9.25±2.38 [9.79] mL/m1.7, P=0.031). This effect was observed independently of blood pressure reduction. Conclusions RD significantly decreases left ventricular mass, while extracellular volume remains stable. Our results suggest that the observed left ventricular mass decrease was due not exclusively to a reversion of myocyte hypertrophy but also to an additional reduction in collagen content, indicating interstitial myocardial fibrosis.

Fusion‐Optimized Intervals (FOI): A New Method to Achieve the Narrowest QRS for Optimization of the AV and VV Intervals in Patients Undergoing Cardiac Resynchronization Therapy

Optimization of atrioventricular (AV) and interventricular (VV) intervals may improve cardiac resynchronization therapy (CRT) response but is a complex task. Fusion with intrinsic conduction may increase the benefit of CRT. The aim was to describe fusion‐optimized intervals (FOI), a new method of optimizing CRT based on QRS duration.

Temporal diffeomorphic free-form deformation for strain quantification in 3D-US images

This paper presents a new diffeomorphic temporal registration algorithm and its application to motion and strain quantification from a temporal sequence of 3D images. The displacement field is computed by forward eulerian integration of a non-stationary velocity field. The originality of our approach resides in enforcing time consistency by representing the velocity field as a sum of continuous spatiotemporal B-Spline kernels. The accuracy of the developed diffeomorphic technique was first compared to a simple pairwise strategy on synthetic US images with known ground truth motion and with several noise levels, being the proposed algorithm more robust to noise than the pairwise case. Our algorithm was then applied to a database of cardiac 3D+t Ultrasound (US) images of the left ventricle acquired from eight healthy volunteers and three Cardiac Resynchronization Therapy (CRT) patients. On healthy cases, the measured regional strain curves provided uniform strain patterns over all myocardial segments in accordance with clinical literature. On CRT patients, the obtained normalization of the strain pattern after CRT agreed with clinical outcome for the three cases.