Cellular replacement strategies using embryonic stem cells (ESCs) and their cardiac derivatives are emerging as novel experimental therapeutic paradigms for the treatment of post-myocardial ...infarction (MI) left ventricular (LV) dysfunction; however, their potential proarrhythmic risk remains unclear.
The purpose of this study was to investigate the functional effect and proarrhythmic risk of ESC transplantation in a mouse model of MI.
We compared the functional effects and proarrhythmic risk of direct intramyocardial transplantation of 3 × 10(5) undifferentiated mouse ESCs (MI+ESC group, n = 33) and mouse ESC-derived cardiomyocytes (MI+ESC-CM group, n = 40) versus culture medium (MI group, n = 33) at the infarct border zone in a mouse model of acute MI. LV performance was assessed with serial cardiac magnetic resonance imaging (MRI) at 1 and 3 week(s) post-MI, and invasive LV pressure measurement was assessed (dP/dt) at 4 weeks before sacrifice for histological examination. Furthermore, electrophysiological study was also performed in another set of animals in each group (n = 24) to assess for proarrhythmias after transplantation.
In vitro cellular electrophysiological study demonstrated that ESC-CMs exhibit arrhythmogenesis including automaticity, lengthened action potential duration, and depolarized resting membrane potential. At 4 weeks, the MI+ESC-CM group (21/40, 53%) had a higher mortality rate compared with those in the MI group (10/33, 30%, P = .08) and in the MI+ESC group (7/33, 21%, P = .012). Electrophysiological study showed a significantly higher incidence of inducible ventricular tachyarrhythmias in the MI+ESC-CM group (13/24, 54%) compared with in the MI group (6/24, 21%, P = .039) and in the MI+ESC group (5/24, 21%, P = .017). Cardiac MRI showed similar improvement in LV ejection fraction in the MI+ESC and MI+ESC-CM groups compared with in the MI group at 1 week (27.5% ± 3.8%; 30.3% ± 5.2% vs. 12.4% ± 1.4%; P < .05) and 3 weeks (29.8% ± 3.9%; 27.0% ± 4.8% vs. 10.6% ± 2.8%; P < .05) post-MI, respectively. Furthermore, invasive hemodynamic assessment at 4 weeks showed significant similar improvement in LV +dP/dt in the MI+ESC (2,644 ± 391 mmHg/s, P < .05) and MI+ESC-CM groups (2,539 ± 389 mmHg/s; P < .05) compared with in the MI group (2,042 ± 406 mmHg/s).
Our results demonstrate that transplantation of undifferentiated ESCs and ESC-CMs provides similar improvement in cardiac function post-MI. However, transplantation of ESC-CMs is associated with a significantly higher prevalence of inducible ventricular tachyarrhythmias and early mortality than transplantations with ESCs.
Fragmented QRS (fQRS) complexes on a routine 12-lead electrocardiogram were associated with adverse cardiac events, including sudden death in patients with coronary artery disease (CAD).
To ...investigate the relationship between the fQRS complex and global and regional left ventricular (LV) functions in patients with CAD.
The study consisted of 176 patients (68 ± 9 years; 145 82% men) with CAD with narrow QRS duration and preserved LV ejection fraction (>45%). All patients underwent detailed 2-dimensional speckle-tracking echocardiography to determine global and segmental (basal, middle, and apical) LV strains and strain rates and were prospectively followed-up in the outpatient clinic.
Fifty-five patients (31%) had fQRS complexes. Global, middle, and apical LV longitudinal, radial, and circumferential strains and strain rates were significantly lower in the fQRS group than in the non-fQRS group (all P <.05). Multivariate logistic regression analysis revealed that the fQRS complex was associated with decreased global circumferential strain (odds ratio 1.19; 95% confidence interval 1.06-1.33; P = .003) and multivessel disease (odds ratio 3.69; 95% confidence interval 1.35-10.08; P = .011). Kaplan-Meier analysis revealed that event-free survival for cardiac events was significantly lower in the fQRS group than in the non-fQRS group (P = .036).
Our results demonstrated that the fQRS complex in patients with CAD with preserved LV ejection fraction was associated with subclinical global and regional LV dysfunctions as detected by 2-dimensional speckle-tracking imaging, and the results also predicted adverse cardiac events.
Background Discharge disposition planning is vital for poststroke patients. We investigated clinical factors associated with discharging patients to nursing homes, using the Taiwan Stroke Registry ...data collected from 39 major hospitals. Methods We randomly assigned 21,575 stroke inpatients registered from 2006 to 2008 into derivation and validation groups at a 3-to-1 ratio. We used the derivation group to develop a prediction model by measuring cumulative risk scores associated with potential predictors: age, sex, hypertension, diabetes mellitus, heart diseases, stroke history, snoring, main caregivers, stroke types, and National Institutes of Health Stroke Scale (NIHSS). Probability of nursing home care and odds ratio (OR) of nursing home care relative to home care by cumulative risk scores were measured for the prediction. The area under the receiver operating characteristic curve (AUROC) was used to assess the model discrimination against the validation group. Results Except for hypertension, all remaining potential predictors were significant independent predictors associated with stroke patient disposition to nursing home care after discharge from hospitals. The risk sharply increased with age and NIHSS. Patients with a cumulative risk score of 15 or more had an OR of 86.4 for the nursing home disposition. The AUROC plots showed similar areas under curves for the derivation group (.86, 95% confidence interval CI, .85-.87) and for the validation group (.84, 95% CI, .83-.86). Conclusions The cumulative risk score is an easy-to-estimate tool for preparing stroke patients and their family for disposition on discharge.
