Single-beat noninvasive imaging of ventricular endocardial and epicardial activation in patients undergoing CRT.

BACKGROUND: Little is known about the effect of cardiac resynchronization therapy (CRT) on endo- and epicardial ventricular activation. Noninvasive imaging of cardiac electrophysiology (NICE) is a novel imaging tool for visualization of both epi- and endocardial ventricular electrical activation. METHODOLOGY/PRINCIPAL FINDINGS: NICE was performed in ten patients with congestive heart failure (CHF) undergoing CRT and in ten patients without structural heart disease (control group). NICE is a fusion of data from high-resolution ECG mapping with a model of the patient's individual cardiothoracic anatomy created from magnetic resonance imaging. Beat-to-beat endocardial and epicardial ventricular activation sequences were computed during native rhythm as well as during ventricular pacing using a bidomain theory-based heart model to solve the related inverse problem. During right ventricular (RV) pacing control patients showed a deterioration of the ventricular activation sequence similar to the intrinsic activation pattern of CHF patients. Left ventricular propagation velocities were significantly decreased in CHF patients as compared to the control group (1.6±0.4 versus 2.1±0.5 m/sec; p<0.05). CHF patients showed right-to-left septal activation with the latest activation epicardially in the lateral wall of the left ventricle. Biventricular pacing resulted in a resynchronization of the ventricular activation sequence and in a marked decrease of total LV activation duration as compared to intrinsic conduction and RV pacing (129±16 versus 157±28 and 173±25 ms; both p<0.05). CONCLUSIONS/SIGNIFICANCE: Endocardial and epicardial ventricular activation can be visualized noninvasively by NICE. Identification of individual ventricular activation properties may help identify responders to CRT and to further improve response to CRT by facilitating a patient-specific lead placement and device programming.

Long-term results of high vs. normal impedance ventricular leads on actual (Real-Life) pacemaker generator longevity.

AIM: The long-term effects of high impedance vs. standard impedance pacing leads on actual generator longevity were studied. METHODS AND RESULTS: In 40 patients (21 females, age 73 +/- 13 years) with standard dual-chamber pacemaker indication, bipolar standard impedance ventricular leads and high-impedance leads were implanted in a randomized fashion. Identical pacemaker generators and atrial pacing leads were implanted in all patients. Patients were observed during a mean follow-up of 89.8 +/- 8.8 months before pacemaker replacement. Initially, the patients who received the high-impedance leads had a lower current drain as compared with standard pacing impedance leads, and the estimated pacemaker longevity was significantly prolonged, too. But this pattern disappeared after 6 years of follow-up, and finally the actual pacemaker generators' replacement time was 86.7 +/- 6.8 months in standard impedance lead group vs. 91.2 +/- 10.3 months in high-impedance lead group (P = 0.17). CONCLUSION: Implantation of high pacing impedance leads for ventricular stimulation does not result in a benefit with respect to pacemaker longevity as compared with standard impedance leads.

3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors improve myocardial high-energy phosphate metabolism in men.

PURPOSE: We intended to prove that 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins have a beneficial impact on the human myocardial, high-energy, phosphate metabolism. METHODS: The present study included 18 male patients (mean age 49.8 +/- 10.3) with statin-treated, familiar hypercholesterolemia (FH) and 13 male patients with untreated FH (mean age 44.6 +/- 9.5). Twenty-six healthy male volunteers served as controls (mean age 44.2 +/- 12.1). Phosphorus-31, two-dimensional chemical shift imaging (31P 2D CSI) of the heart was performed in all subjects using a 1.5 Tesla whole-body magnetic resonance (MR) scanner. The ratios between phosphocreatine (PCr) and beta-adenosine-triphosphate (beta-ATP) were calculated for the left ventricular myocardium. Furthermore, echocardiographic evaluation and stress tests were performed in all individuals. RESULTS: The untreated patients with FH exhibited a significant decrease in left ventricular PCr to beta-ATP ratios (1.78 +/- 0.34) compared with statin-treated FH patients (2.15 +/- 0.26, p < 0.001) and healthy controls (2.04 +/- 0.26, p = 0.009). The left ventricular PCr-to-beta-ATP ratios of the treated FH patients were in the range of the healthy controls. CONCLUSIONS: Our study shows for the first time an-improvement of the high-energy, phosphate metabolism in the left ventricular myocardium of patients with statin-treated FH compared with untreated FH patients.

Effects of oral magnesium therapy on exercise tolerance, exercise-induced chest pain, and quality of life in patients with coronary artery disease.

Previous studies have demonstrated that magnesium supplementation improves endothelial function in patients with coronary artery disease (CAD). However, the impact on clinical outcomes, such as exercise-induced chest pain, exercise tolerance, and quality of life, has not been established. In a multicenter, multinational, prospective, randomized, double-blind and placebo-controlled trial, 187 patients with CAD (151 men, 36 women; mean +/- SD age 63 +/- 10 years, range 42 to 83) were randomized to receive either oral magnesium 15 mmol twice daily (Magnosolv-Granulat, total magnesium 365 mg provided as magnesium citrate) (n = 94) or placebo (n = 93) for 6 months. Symptom-limited exercise testing (Bruce protocol) and responses given on quality-of-life questionnaires were the outcomes measured. Magnesium therapy significantly increased intracellular magnesium levels ([Mg]i) in a substudy of 106 patients at 6 months compared with placebo (35.5 +/- 3.7 vs 32.6 +/- 2.9 mEq/L, p = 0.0151). Magnesium treatment significantly increased exercise duration time compared with placebo (8.7 +/- 2.1 vs 7.8 +/- 2.9 minutes, p = 0.0075), and lessened exercise-induced chest pain (8% vs 21%, p = 0.0237). Quality-of-life parameters significantly improved in the magnesium group. These findings suggest that oral magnesium supplementation in patients with CAD for 6 months results in a significant improvement in exercise tolerance, exercise-induced chest pain, and quality of life, suggesting a potential mechanism whereby magnesium could beneficially alter outcomes in patients with CAD.

Clinical ECG mapping and imaging of cardiac electrical excitation.

Combining electrocardiographic mapping and 3D+time anatomical data enables noninvasively the imaging of the electrical excitation sequence in the human heart. A bidomain-theory based surface heart model activation time imaging approach was employed to image single beat data of atrial and ventricular depolarisation. Activation time maps were reconstructed for three patients who underwent an electrophysiologic study. The sinus rhythm and a rhythm according to a pacing protocol were reconstructed for two patients. For the third patient the accessory pathway of the WPW syndrome was localized. For focal arrhythmias, this model-based imaging approach might allow the guidance and evaluation of antiarrhythmic interventions, for instance, in case of catheter ablation or drug therapy.