The impact of semi-automatic versus manually adjusted assessment of global longitudinal strain in post-myocardial infarction patients.

There are unresolved questions related to the proper use of editing the region of interest (ROI) for measurements of global longitudinal strain (GLS). The purpose of the present study was to compare the semi-automatic default GLS value by the vendor's software with manually adjusted GLS and test the impact on GLS measures with different ROI widths. We selected 25 patients post myocardial infarction treated with PCI who had excellent echocardiographic recordings after 2-5 days and 3 months. The different GLS values were assessed from these 50 analyses in three steps. The semi-automatically GLS by default ROIs was compared with manually adjusted ROIs widths selected by an expert and then with manual adjustments, but with fixed ROIs being narrow, medium and wide. Their mean age was 64 (± 12) years, 52% had ST elevation MI and mean LVEF was 52 (± 4)%. Mean default GLS was - 15.3 (± 2.5)% with the widest ROI level selected semi-automatically in 78% of all widths. The mean expert GLS with manually adjusted ROI was - 14.7 (± 2.4)%, and the medium ROI level was selected by the expert in 85% of all examinations. The mean adjusted GLS, but with fixed ROIs widths was - 15.0 (± 2.5%)% with narrow ROI, - 14.7 (± 2.6)% with medium and - 13.5 (± 2.3)% with wide ROI width (p < 0.001 vs. default GLS). The Intra Class Coefficient Correlation between default and manually adjusted expert GLS was 0.93 (p < 0.001). The difference between the default and the manually adjusted expert GLS was neglectable. These findings may represent a simplification of the assessment of GLS that might increase its use in clinical practice. The GLS measurements with a fixed wide ROIs were significantly different from the expert measurements and indicate that a wide ROI should be avoided.

Prevalence and Outcome of High-Risk QT Prolongation Recorded in the Emergency Department from an Institution-Wide QT Alert System.

BACKGROUND: QT prolongation is an independent risk factor for sudden death, stroke, and all-cause mortality. However, additional studies have shown that in certain settings, QT prolongation may be transient and a result of external factors. OBJECTIVE: In this study, we evaluated the clinical characteristics and outcomes of patients seen in the emergency department (ED) with QT prolongation. METHODS: Between November 2010 and June 2011, 7522 patients had an electrocardiogram (ECG) obtained during their evaluation in the ED. Clinical, laboratory, and therapeutic information was collected for all patients with QT prolongation (i.e., ≥ 500 ms and QRS < 120 ms). Potential QT-inciting factors (drugs, electrolyte disturbances, and comorbidities) were synthesized into a pro-QT score. RESULTS: Among the 7522 patients with an ECG obtained in the ED, a QT alert was activated in 93 (1.2%; mean QTc 521 ± 34 ms). The majority of ED patients (64%) had more than one underlying condition associated with QT prolongation, with electrolyte disturbances in 51%, a QT prolonging condition in 56%, and QT-prolonging drugs in 77%. Thirty-day mortality was 13% for patients with QT prolongation noted in the ED. CONCLUSIONS: One percent of patients evaluated with an ECG in the ED activated our prolonged QTc warning system, with most demonstrating > 1 QT-prolonging condition. Thirty-day mortality was significant, but it requires further investigation to determine whether the QTc simply provided a non-invasive indicator of increased risk or heralded the presence of a vulnerable host at risk of a QT-mediated sudden dysrhythmic death.

Whole exome sequencing with genomic triangulation implicates CDH2-encoded N-cadherin as a novel pathogenic substrate for arrhythmogenic cardiomyopathy.

BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a heritable disease characterized by fibrofatty replacement of cardiomyocytes, has a prevalence of approximately 1 in 5000 individuals, and accounts for approximately 20% of sudden cardiac death in the young (≤35 years). ACM is most often inherited as an autosomal dominant trait with incomplete penetrance and variable expression. While mutations in several genes that encode key desmosomal proteins underlie about half of all ACM, the remainder is elusive genetically. OBJECTIVE: Here, whole exome sequencing (WES) was performed with genomic triangulation in an effort to identify a novel explanation for a phenotype-positive, genotype-negative multi-generational pedigree with a presumed autosomal dominant, maternal inheritance of ACM. METHODS: WES and genomic triangulation was performed on a symptomatic 14-year-old female proband, her affected mother and affected sister, and her unaffected father to elucidate a novel ACM-susceptibility gene for this pedigree. Following variant filtering using Ingenuity® Variant Analysis, gene priority ranking was performed on the candidate genes using ToppGene and Endeavour. The phylogenetic and physiochemical properties of candidate mutations were assessed further by 6 in silico prediction tools. Species alignment and amino acid conservation analysis was performed using the Uniprot Consortium. Tissue expression data was abstracted from Expression Atlas. RESULTS: Following WES and genomic triangulation, CDH2 emerged as a novel, autosomal dominant, ACM-susceptibility gene. The CDH2-encoded N-cadherin is a cell-cell adhesion protein predominately expressed in the heart. Cardiac dysfunction has been demonstrated in prior CDH2 knockout and over-expression animal studies. Further in silico mutation prediction, species conservation, and protein expression analysis supported the ultra-rare (minor allele frequency <0.005%) p.Asp407Asn-CDH2 variant as a likely pathogenic variant. CONCLUSIONS: Herein, it is demonstrated that genetic mutations in CDH2-encoded N-cadherin may represent a novel pathogenetic basis for ACM in humans. The prevalence of CDH2-mediated ACM in heretofore genetically elusive ACM remains to be determined.

Comparison of Electrocardiography Markers and Speckle Tracking Echocardiography for Assessment of Left Ventricular Myocardial Scar Burden in Patients With Previous Myocardial Infarction.

Myocardial scar burden is an important prognostic factor after myocardial infarction. This cohort study compared assessment of left ventricle scar burden between pathological Q waves on electrocardiography (ECG), Selvester multiparametric ECG scoring system for scar burden, and global longitudinal strain (GLS) by speckle-tracking echocardiography 6 months after myocardial infarction. The scar burden was defined by late gadolinium enhancement cardiac magnetic resonance as fraction of total left ventricle tissue. ECG measures were presence of pathologic Q waves and Selvester scores. GLS was the average of peak strain from 16 left ventricle segments. In 34 patients aged 58 ± 10 years (mean ± SD), the scar burden was 19% (9, 26) (median [quartiles]) and 79% had scar burden >5%. Patients with scar burden >5% more frequently had pathologic Q waves (63% vs 14%) and had worse Selvester scores (5 [3, 7] vs 0 [0, 1]) and worse GLS (-16.6 ± 2.4% vs -19.9 ± 1.1%). Pathologic Q waves, Selvester scores, ejection fraction, and GLS related to scar burden in univariable analyses. Sensitivity and specificity for detecting scar burden >5% was 63% and 86% (pathologic Q waves), 89% and 86% (Selvester score), 81% and 86% (ejection fraction), 89% and 86% (GLS), and 96% and 71% (combination of Q waves, Selvester score, and GLS). In conclusion, Selvester score and GLS related to scars 6 months after myocardial infarction, and pathologic Q waves were only weakly associated with scar and GLS was associated with scar independently of ECG markers.

Strain echocardiographic assessment of left atrial function predicts recurrence of atrial fibrillation.

AIMS: We evaluated if a dispersed left atrial (LA) contraction pattern was related to atrial fibrillation (AF) in patients with normal left ventricular (LV) function, and normal or mildly enlarged left atrium. METHODS AND RESULTS: We included 61 patients with paroxysmal AF (PAF). Of these, 30 had not while 31 had recurrence of AF after radiofrequency ablation (RFA). Twenty healthy individuals were included for comparison. Echocardiography was performed in patients in sinus rhythm the day before RFA. LA volume was calculated. Peak negative longitudinal strain was assessed in 18 LA segments during atrial systole. Contraction duration in 18 LA segments was measured as the time from peak of the P wave on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of contraction durations was defined as LA mechanical dispersion (LA MD). LA size was rather preserved in patients with PAF (LA volume 25 ± 10 mL/m(2)). LA MD was more pronounced in patients with recurrence of AF after RFA compared with those without recurrence and controls (38 ± 14 ms vs. 30 ± 12 ms vs. 16 ± 8 ms, both P < 0.001). LA MD was a predictor of PAF [OR 7.84 (95%CI 2.15-28.7), P < 0.01, per 10 ms increase] adjusted for age, LA volume, e', and LA function. LA function by strain was reduced in both patients with and without recurrent AF after RFA compared with controls (-14 ± 4% vs. -16 ± 3% vs. -19 ± 2%, both P < 0.05). CONCLUSION: LA MD was pronounced, and LA deformation was reduced in patients with PAF with apparently normal LV structure and function, and normal or mildly enlarged LA. LA MD may be useful as a predictor of AF recurrence after RFA.

Noninvasive assessment of myocardial fibrosis in patients with obstructive hypertrophic cardiomyopathy.

OBJECTIVE: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown. The aim of this study was to assess the ability of LGE and strain echocardiography to detect type and extent of myocardial fibrosis in obstructive HCM patients undergoing septal myectomy. METHODS: Thirty-two HCM patients (age 60±10) were included in this cross-sectional study and preoperatively examined by speckle-tracking strain echocardiography and LGE-CMR (n=21). Histological fibrosis was classified as interstitial, replacement and total. RESULTS: Histological fibrosis was present in 31 patients. The percentage of total, interstitial and replacement fibrosis was 15(7, 31)%, 11(5, 24)% and 3(1, 6)%, respectively. Reduced longitudinal septal strain correlated with total (r=0.50, p=0.01) and interstitial (r=0.40, p=0.03), but not with replacement fibrosis (r=0.28, p=0.14). Septal LGE was detected in 13/21 (62%), but percentage LGE did not correlate with total fibrosis (r=0.25, p=0.28). Extent of fibrosis did not differ between patients with and without septal LGE (20(9, 58)% versus 14(5, 19)% p=0.41). Patients with ventricular arrhythmias (n=8) had lower septal longitudinal strain and increased extent total and interstitial fibrosis in myectomy specimens, but no differences were demonstrated in LGE. Reduced longitudinal septal strain and increased extent of interstitial fibrosis predicted ventricular arrhythmias independently of age and gender. CONCLUSIONS: In myectomised HCM patients, reduced longitudinal septal strain correlated better with interstitial and total fibrosis in myectomy specimens, and was a more powerful tool to predict arrhythmias than LGE.

Risk assessment of ventricular arrhythmias in patients with nonischemic dilated cardiomyopathy by strain echocardiography.

BACKGROUND: Indications for prophylactic implantable cardioverter-defibrillator implantation in patients with nonischemic dilated cardiomyopathy (DCM) are based on left ventricular (LV) ejection fraction (LVEF), although LVEF has limited ability to predict arrhythmias. It has recently been shown that strain echocardiography can predict ventricular arrhythmias in patients after myocardial infarction. The aim of this study was to evaluate whether strain echocardiography may help in the risk stratification of ventricular arrhythmias in patients with DCM. METHODS: Ninety-four patients with nonischemic DCM were prospectively included. By speckle-tracking strain echocardiography, global longitudinal strain was calculated as the average of peak longitudinal strain from a 16-segment LV model. The time interval from electrocardiographic peak R to peak negative strain was assessed in each LV segment. Mechanical dispersion was defined as the standard deviation of time to peak negative strain from 16 LV segments. RESULTS: After a median of 22 months of follow-up (range, 1-46 months), 12 patients (13%) had experienced arrhythmic events, defined as sustained ventricular tachycardia or cardiac arrest. LVEF and global longitudinal strain were reduced in patients with DCM with arrhythmic events compared with those without (28 ± 10% vs 38 ± 13%, P = .01, and -6.4 ± 3.3% vs -12.3 ± 5.2%, P < .001, respectively). Global longitudinal strain showed greater area under the curve than LVEF to identify arrhythmic events in receiver operating characteristic curve analyses (P = .05). Patients with arrhythmic events had increased mechanical dispersion (98 ± 43 vs 56 ± 18 ms, P < .001). Mechanical dispersion predicted arrhythmias independently of LVEF (hazard ratio, 1.28; 95% confidence interval, 1.11-1.49; P = .001). CONCLUSIONS: Global longitudinal strain is a promising marker of arrhythmias. Mechanical dispersion predicted arrhythmic events in patients with DCM independently of LVEF. Strain echocardiography may help in the risk stratification of patients with DCM not fulfilling current implantable cardioverter-defibrillator indications.