Search

Metabolic and mechanical stress in the failing heart activates the cardiac sympathetic afferent reflex (CSAR). It has been demonstrated that cardiac resynchronization therapy (CRT) acutely reduces MSNA in clinical responders. Mechanistically, this beneficial effect might be explained by acute deactivation of the CSAR. In addition to sympathoexcitation, CSAR inhibits the arterial baroreflex at the level of the nucleus tractus solitarii. Hence, in responders, CRT is likely to remove/reduce this inhibition. Therefore, we hypothesized that CRT acutely facilitates the arterial baroreflex. One day after implantation of a CRT device in 32 patients with chronic heart failure (LVEF; 27 [+ or -] 6%), we measured noninvasive baroreflex sensitivity (BRS) and heart rate variability (HRV) in two conditions: CRT device switched on and switched off (on/off order randomized). BRS changes were correlated with the difference in unpaced/paced LVEF, a measure of acute mechanical response to CRT. CRT increased BRS by 35% from 2.96 to 3.79 ms/mmHg (P < 0.02) and increased HRV (standard deviation of the intervals between normal beats) from 18.5 to 24.0 ms (P < 0.01). The CRT-induced relative change in BRS correlated with the change in LVEF (r = 0.44; P < 0.01). In conclusion, CRT acutely increases BRS and HRV. This favorable response of the autonomic nervous system might be caused by CRT-induced CSAR deactivation. Follow-up studies should verify the mechanism of the acute response and the possible predictive value of an acute positive BRS response. baroreflex sensitivity; heart rate variability; cardiac resynchronization therapy; cardiac sympathetic afferent reflex

The study aimed to assess whether the 12-lead ECG-derived ventricular gradient, a vectorial representation of ventricular action potential duration heterogeneity directed toward the area of shortest action potential duration, can improve ECG diagnosis of chronic right ventricular (RV) pressure load. ECGs from 72 pulmonary arterial hypertension patients recorded 1 with R > 0.5 mV in V1, and QRS axis >90[degrees]) had a sensitivity of 89% and a specificity of 93% for presence of chronic RV pressure load. However, the ventricular gradient not only had a higher diagnostic accuracy for chronic RV pressure load by receiver operating characteristic analysis [areas under the curve (AUC) = 0.993, SE 0.004 vs. AUC = 0.945, SE 0.021, P < 0.05], but also discriminated between mild-to-moderate and severe RV pressure load. CMR identified an inverse relation between the ventricular gradient and RV mass, and a trend toward a similar relation with RV volume. In conclusion, chronically increased RV pressure load is electrocardiographically reflected by an altered ventricular gradient associated with RV remodeling-related changes in ventricular action potential duration heterogeneity. The use of the ventricular gradient allows ECG detection of even mildly increased RV pressure load. hypertension; pulmonary; right ventricular hypertrophy; diagnosis; ventricular gradient; electrocardiogram

Mesenchymal stem cells (MSCs) from healthy donors improve cardiac function in experimental acute myocardial infarction (AMI) models. However, little is known about the therapeutic capacity of human MSCs (hMSCs) from patients with ischemic heart disease (IHD). Therefore, the behavior of hMSCs from IHD patients in an immunecompromised mouse AMI model was studied. Enhanced green fluorescent protein-labeled hMSCs from IHD patients (hMSC group: 2 x [10.sup.5] cells in 20 [micro]l, n = 12) or vehicle only (medium group: n = 14) were injected into infarcted myocardium of NOD/scid mice. Sham-operated mice were used as the control (n = 10). Cardiac anatomy and function were serially assessed using 9.4-T magnetic resonance imaging (MRI); 2 wk after cell transplantation, immunohistological analysis was performed. At day 2, delayed-enhancement MRI showed no difference in myocardial infarction (MI) size between the hMSC and medium groups (33 [+ or -] 2% vs. 36 [+ or -] 2%: P = not significant). A comparable increase in left ventricular (LV) volume and decrease in ejection fraction (EF) was observed in both MI groups. However, at day 14, EF was higher in the hMSC than in the medium group (24 [+ or -] 3% vs. 16 [+ or -] 2%; P < 0.05). This was accompanied by increased vascularity and reduced thinning of the infarct scar. Engrafted hMSCs (4.1 [+ or -] 0.3% of injected cells) expressed von Willebrand factor (16.9 [+ or -] 2.7%) but no stringent cardiac or smooth muscle markers. hMSCs from patients with IHD engraft in infarcted mouse myocardium and preserve LV function 2 wk after AMI, potentially through an enhancement of scar vascularity and a reduction of wall thinning. magnetic resonance imaging; cell therapy; animal model

The study aim was to assess three-dimensional electrocardiogram (ECG) changes during development of pulmonary arterial hypertension (PAH). PAH was induced in male Wistar rats (n = 23) using monocrotaline (MCT; 40 mg/kg sc). Untreated healthy rats served as controls (n = 5). ECGs were recorded with an orthogonal three-lead system on days O, 14, and 25 and analyzed with dedicated computer software. In addition, left ventricular (LV)-to-right ventricular (RV) fractional shortening ratio was determined using echocardiography. Invasively measured RV systolic pressure was 49 (SD 10) mmHg on day 14 and 64 (SD 10) mmHg on day 25 vs. 25 (SD 2) mmHg in controls (both P < 0.001). Baseline ECGs of controls and MCT rats were similar, and ECGs of controls did not change over time. In MCT rats, ECG changes were already present on day 14 but more explicit on day 25: increased RV electromotive forces decreased mean QRS-vector magnitude and changed QRS-axis orientation. Important changes in action potential duration distribution and repolarization sequence were reflected by a decreased spatial ventricular gradient magnitude and increased QRS-T spatial angle. On day 25, LV-to-RV fractional shortening ratio was increased, and RV hypertrophy was found, but not on day 14. In conclusion, developing PAH is characterized by early ECG changes preceding RV hypertrophy, whereas severe PAH is marked by profound ECG changes associated with anatomical and functional changes in the RV. Three-dimensional ECG analysis appears to be very sensitive to early changes in RV afterload. fight ventricular hypertrophy; monocrotaline; electrocardiogram

Mechanical dyssynchrony is an important codeterminant of cardiac dysfunction in heart failure. Treatment, either medical, surgical, or by pacing, may improve cardiac function partly by improving mechanical synchrony. Consequently, the quantification of ventricular mechanical (dys)synchrony may have important diagnostic and prognostic value and may help to determine optimal therapy. Therefore, we introduced new indexes to quantify temporal and spatial aspects of mechanical dyssynchrony derived from online segmental conductance catheter signals obtained during diagnostic cardiac catheterization. To test the feasibility and usefulness of our approach, we determined cardiac function and left ventricular mechanical dyssynchrony by the conductance catheter in heart failure patients with intraventricular conduction delay (n = 12) and in patients with coronary artery disease (n = 6) and relatively preserved left ventricular function. The heart failure patients showed depressed systolic and diastolic function. However, the most marked hemodynamic differences between the groups were found for mechanical dyssynchrony, indicating a high sensitivity and specificity of the new indexes. Comparison of conductance catheter-derived indexes with septal-to-lateral dyssynchrony derived by tissue-Doppler velocity imaging showed highly significant correlations. The proposed indexes provide additional, new, and quantitative information on temporal and spatial aspects of mechanical dyssynchrony. They may refine diagnosis of cardiac dysfunction and evaluation of interventions, and ultimately help to select optimal therapy. ventricular function