Multi-parametric analyses to investigate dependencies of normal left atrial strain by cardiovascular magnetic resonance feature tracking

Left-atrial (LA) strain is the result of complex hemodynamics, which may be better characterized using a multiparametric approach. Cardiovascular magnetic resonance (CMR) feature tracking was used to perform a comprehensive LA strain assessment of 183 enrolled healthy volunteers (11–70 years, 97 females, median 32.9 $\pm$ 28.3 years). Novel strain dependencies were assessed using multi-parametric regression (MPR) analyses. LA volumetric data, left ventricular strain, transmitral and pulmonary venous blood flow parameters were utilized to create clusters for MPR of all subjects and a heart rate controlled subgroup (pulse: 60–75/min, N = 106). The LA reservoir(r) and conduit(c) strains of the total cohort were significantly elevated (p $\leq$ 0.001) in women (r: 49.7 $\pm$ 12.9%, c: 32.0 $\pm$ 11.0%) compared to men (r: 42.9 $\pm$ 11.4%, c: 26.1 IQ 10.5%). In contrast, there were no gender-specific differences (p > 0.05) for subgroup LA reservoir, conduit and booster(b) strains (all, r: 47.3 $\pm$ 12.7%; c: 29.0 IQ 15.5%; b: 17.6 $\pm$ 5.4%) and strain rates (all, 2.1 IQ 1.0 $s^{−1}$; − 2.9 IQ 1.5 $s^{−1}$; − 2.3 IQ 1.0 $s^{−1}$). MPR found large effect sizes (|$R^{2}$|$\geq$ 0.26) for correlations between strain and various cardiac functional parameters. Largest effect size was found for the association between LA conduit strain and LA indexed booster volume, LA total ejection fraction, left ventricular global radial strain and E-wave (|$R^{2}$|= 0.437). In addition to providing normal values for sex-dependent LA strain and strain rate, no gender differences were found with modified heart rate. MPR analyses of LA strain/strain rate and various cardiac functional parameters revealed that heart rate control improved goodness-of-fit for the overall model

Left-ventricular reference myocardial strain assessed by cardiovascular magnetic resonance feature tracking and fSENC

$\bf Aims:$ Cardiac strain parameters are increasingly measured to overcome shortcomings of ejection fraction. For broad clinical use, this study provides reference values for the two strain assessment methods feature tracking (FT) and fast strain-encoded (fSENC) cardiovascular magnetic resonance (CMR) imaging, including the child/adolescent group and systematically evaluates the influence of temporal resolution and muscle mass on strain. $\textbf {Methods and Results:}$ Global longitudinal (GLS), circumferential (GCS), and radial (GRS) strain values in 181 participants (54% women, 11–70 years) without cardiac illness were assessed with FT (CVI42® software). GLS and GCS were also analyzed using fSENC (MyoStrain® software) in a subgroup of 84 participants (60% women). Fourteen patients suffering hypertrophic cardiomyopathy (HCM) were examined with both techniques. CMR examinations were done on a 3.0T MR-system. FT-GLS, FT-GCS, and FT-GRS were −16.9 $\pm$ 1.8%, −19.2 $\pm$ 2.1% and 34.2 $\pm$ 6.1%. fSENC-GLS was higher at −20.3 $\pm$ 1.8% ($\it p$ < 0.001). fSENC-GCS was comparable at−19.7 $\pm$ 1.8% ($\it p$ = 0.06). All values were lower in men ($\it p$ < 0.001). Cardiac muscle mass correlated ($\it p$ < 0.001) with FT-GLS ($\it r$ = 0.433), FT-GCS ($\it r$ = 0.483) as well as FT-GRS ($\it r$ = −0.464) and acts as partial mediator for sex differences. FT-GCS, FT-GRS and fSENC-GLS correlated weakly with age. FT strain values were significantly lower at lower cine temporal resolutions, represented by heart rates ($\it r$ = −0.301, −0.379, 0.385) and 28 or 45 cardiac phases per cardiac cycle (0.3–1.9% differences). All values were lower in HCM patients than in matched controls ($\it p$ < 0.01). Cut-off values were −15.0% (FT-GLS), −19.3% (FT-GCS), 32.7% (FT-GRS), −17.2% (fSENC-GLS), and −17.7% (fSENC-GCS). $\bf Conclusion:$ The analysis of reference values highlights the influence of gender, temporal resolution, cardiac muscle mass and age on myocardial strain values

Pre-operative risk factors for driveline infection in left ventricular-assist device patients

$\bf Aims$ Implantation of left ventricular-assist devices (LVAD) to treat end-stage heart failure is of increasing relevance due to donor shortage. Infections of the driveline are common adverse events. LVAD infections can lead to high urgency listings for transplantation. However, transplantation in patients with infection leads to worse post-transplantation outcomes. This study aims to evaluate specific risk factors for driveline infections at the time of implantation. $\textbf {Methods and results}$ Four hundred forty-one patients receiving either Heartmate II or Heartware system from August 2009 to October 2013 were assessed. An expert committee sorted patients into four different groups concerning the likeliness of infection. Twenty-eight (6%) of discussed infection cases were judged as secured, 33 (7%) as likely, 18 (4%) as possible, and 20 (4%) as unlikely. The remaining 342 (78%) subjects showed either no signs of infection at all times (329 [75%]) or developed signs of infection in a second observation period within 1 year after ending of the first observation period (13 [3%]). For a better discriminatory power, cases of secured and likely infections were tested against the group with no infection at all times in a Cox proportional hazard model. Among all variables tested by univariate analysis (significance level $\it P$ < 0.15), only age ($\it P$ = 0.07), LVAD-type ($\it P$ = 0.12), need for another thoracic operation ($\it P$ = 0.02), and serum creatinine value ($\it P$ = 0.02) reached statistical significance. These were subsequently subjected to multivariate analysis to calculate the cumulative risk of developing a drive infection. The multivariate analysis showed that of all the potential risk factors tested, only the necessity of re-thoracotomy or secondary thoracic closure had a significant, protective effect (hazard ratio [95% CI] = 0.45 [0.21–0.95]; $\it P$ = 0.04). $\bf Conclusion$ This single-centre cohort study shows that driveline infections are common adverse events. The duration of support represents the major risk factor for LVAD driveline infections

Assessment of pulmonary artery stiffness by multiparametric cardiac magnetic resonance-surrogate for right heart catheterization

$\bf Background:$ Cardiac magnetic resonance (CMR) imaging allows for multiparametric assessment of healthy pulmonary artery (PA) hemodynamics. Gender- and aging-associated PA stiffness and pressure alterations have remained clinically unestablished, however may demonstrate epidemiological differences in disease development. The aim of this study is to evaluate the role of CMR as a surrogate for catheter examinations by providing a comprehensive CMR assessment of sex- and age-related reference values for PA stiffness, flow, and pressure. $\textbf {Methods and Results:}$ PA hemodynamics were studied between gender and age groups (>/50 years) exhibited reduced PA elasticity (41.7% [31.0; 52.9] vs. 66.4% [47.7; 83.0]; $\it P$ < 0.001), reduced PA compliance (15.4 $mm^{2}$/mmHg [12.3; 20.7] vs. 21.3 $\pm$ 6.8 $mm^{2}$/mmHg; $\it P$ < 0.001), higher pulse wave velocity (2.59 m/s [1.57; 3.59] vs. 1.76 m/s [1.24; 2.34]; $\it P$ < 0.001) and a reduced FWHM (218 $\pm$ 29 ms vs. 231 $\pm$ 21 ms; $\it P$ < 0.001) than younger subjects. $\bf Conclusions:$ Velocity-time profiles are dependent on age and gender. PA stiffness indices deteriorate with age. CMR has potential to serve as a surrogate for right heart catheterization

CMR-based right ventricular strain analysis in cardiac amyloidosis and its potential as a supportive diagnostic feature

$\it Background:$ Right ventricular (RV) strain has provided valuable prognostic information for patients with $\underline {cardiac amyloidosis}$ (CA). However, the extent to which RV strain and strain rate can differentiate CA is not yet clinically established. CA underdiagnosis delays treatment strategies and exacerbates patient prognosis. $\it Aims:$ Evaluation of $\underline {cardiac magnetic resonance}$ (CMR) quantified RV global and regional strain of CA and $\underline {HCM}$ patients along with CA subtypes. $\it Methods:$ CMR feature tracking attained longitudinal, radial and circumferential global and regional strain in 47 control subjects (CTRL), 43 CA-, 20 hypertrophic cardiomyopathy- (HCM) patients. CA patients were subdivided in 21 transthyretin-related amyloidosis (ATTR) and 20 acquired immunoglobulin light chain (AL) patients. Strain data and baseline clinical parameters were statistically analysed with respect to $\underline {diagnostic performance}$ and discriminatory power between the different clinical entities. $\it Results:$ Effective differentiation of CA from HCM patients was achieved utilizing global longitudinal (GLS: 16.5 $\pm$ 3.9% vs. −21.3 $\pm$ 6.7%, p = 0.032), radial (GRS: 11.7 $\pm$ 5.3% vs. 16.5 $\pm$ 7.1%, p < 0.001) and circumferential (GCS: -7.6 $\pm$ 4.0% vs. −9.4 $\pm$ 4.4%, p = 0.015) right ventricular strain. Highest strain-based hypertrophic phenotype differentiation was attained using GRS (AUC = 0.86). Binomial regression found right $\underline {ventricular ejection fraction}$ (RV-EF) (p = 0.017) to be a significant predictor of CA-HCM differentiation. CA subtypes had comparable cardiac strains. $\it Conclusion:$ CMR-derived RV global strains and various regional longitudinal strains provide discriminative radiological features for CA-HCM differentiation. However, in terms of feasibility, cine-derived RV-EF quantification may suffice for efficient differential diagnostic support

The desmin mutation DES\it DES-c.735G>C causes severe restrictive cardiomyopathy by inducing in-frame skipping of exon-3

Currently, little is known about the genetic background of restrictive cardiomyopathy (RCM). Herein, we screened an index patient with RCM in combination with atrial fibrillation using a next generation sequencing (NGS) approach and identified the heterozygous mutation $\it DES$-c.735G>C. As $\it DES$-c.735G>C affects the last base pair of exon-3, it is unknown whether putative missense or splice site mutations are caused. Therefore, we applied nanopore amplicon sequencing revealing the expression of a transcript without exon-3 in the explanted myocardial tissue of the index patient. Western blot analysis verified this finding at the protein level. In addition, we performed cell culture experiments revealing an abnormal cytoplasmic aggregation of the truncated desmin form (p.D214-E245del) but not of the missense variant (p.E245D). In conclusion, we show that $\it DES$-c.735G>C causes a splicing defect leading to exon-3 skipping of the $\it DES$ gene. $\it DES$-c.735G>C can be classified as a pathogenic mutation associated with RCM and atrial fibrillation. In the future, this finding might have relevance for the genetic understanding of similar cases

Machine-learning-based diagnostics of cardiac sarcoidosis using multi-chamber wall motion analyses

Background: Hindered by its unspecific clinical and phenotypical presentation, cardiac sarcoidosis (CS) remains a challenging diagnosis. Objective: Utilizing cardiac magnetic resonance imaging (CMR), we acquired multi-chamber volumetrics and strain feature tracking for a support vector machine learning (SVM)-based diagnostic approach to CS. Method: Forty-five CMR-negative (CMR(−), 56.5(53.0;63.0)years), eighteen CMR-positive (CMR(+), 64.0(57.8;67.0)years) sarcoidosis patients and forty-four controls (CTRL, 56.5(53.0;63.0)years)) underwent CMR examination. Cardiac parameters were processed using the classifiers of logistic regression, KNN(K-nearest-neighbor), DT (decision tree), RF (random forest), SVM, GBoost, XGBoost, Voting and feature selection. Results: In a three-cluster analysis of CTRL versus vs. CMR(+) vs. CMR(−), RF and Voting classifier yielded the highest prediction rates (81.82%). The two-cluster analysis of CTRL vs. all sarcoidosis (All Sarc.) yielded high prediction rates with the classifiers logistic regression, RF and SVM (96.97%), and low prediction rates for the analysis of CMR(+) vs. CMR(−), which were augmented using feature selection with logistic regression (89.47%). Conclusion: Multi-chamber cardiac function and strain-based supervised machine learning provides a non-contrast approach to accurately differentiate between healthy individuals and sarcoidosis patients. Feature selection overcomes the algorithmically challenging discrimination between CMR(+) and CMR(−) patients, yielding high accuracy predictions. The study findings imply higher prevalence of cardiac involvement than previously anticipated, which may impact clinical disease management

Cardiovascular magnetic resonance imaging-based right atrial strain analysis of cardiac amyloidosis

$\bf Background:$ Cardiac amyloidosis (CA) manifests in a hypertrophic phenotype with a poor prognosis, making differentiation from hypertrophic cardiomyopathy (HCM) challenging and delaying early treatment. The extent to which magnetic resonance imaging (MRI) quantifies the right atrial strain (RAS) and strain rate (RASR), providing valuable diagnostic information, is not yet clinically established. $\bf Aims:$ This study assesses diagnostic differences in the longitudinal RAS and RASR between CA and HCM patients, control subjects (CTRL) and CA subtypes in addition to the impact of atrial fibrillation (AF) on the right atrial function in CA patients. The RAS and RASR of tricuspid regurgitation (TR) patients are used to assess the potential for diagnostic overlap. $\bf Methods:$ RAS and RASR quantification was conducted via MRI feature-tracking for biopsy-confirmed CA patients with subtypes identified. Strain parameters were compared for CTRL, HCM and TR patients. Post hoc testing identified intergroup differences. $\bf Results:$ In total, 41 CA patients were compared to 47 CTRL, 20 HCM and 31 TR patients. Reservoir (R), conduit and booster RAS and RASRs allow for significant differentiation ($\it p$ 0.8). CA patients with AF, in contrast to sinus rhythm, demonstrated a significantly impaired reservoir RAS and RASR and booster RASR. The discriminative power of RAS for CA vs. TR was insufficient (R: 10.6% $\pm$ 14.3% vs. 7.0% $\pm$ 6.0%, $\it p$ = 0.069). Differentiation between 21 transthyretin and 20 light-chain amyloidosis subtypes was not achievable (R: 0.7% $\pm$ 1.0% vs. 0.7% $\pm$ 1.0%, $\it p$ = 0.827). $\bf Conclusion:$ The MRI-derived RAS and RASR are impaired in CA patients and may support noninvasive differentiation between CA, HCM and CTRL