Effects of Stimulation Site on Diastolic Function in Cardiac Resynchronization Therapy

Background : Cardiac resynchronization therapy (CRT) improves left ventricular (LV) systolic function and clinical status, and prolongs survival of patients suffering from heart failure. An optimal LV site selection is key with respect to improvements in systolic function, though whether a site-specific effect on diastolic function exists is unclear. This study compared the effects of CRT on changes in systolic and diastolic function from 2 LV stimulation sites.
Methods : We studied 21 patients in New York Heart Association functional classes ≥III, and a LV ejection fraction <0.30 and QRS duration > 130 ms. CRT leads were placed in the right ventricle, right atrium, and coronary sinus tributaries. LV stimulation was applied from the postero-lateral and antero-lateral wall. A LV conductance catheter was used to measure LV systolic and diastolic function. Systolic responders had >10% changes in dP/dt_max, and diastolic responders <10% changes in τ during CRT versus baseline. Response was highly dependent on LV lead position for both diastolic and systolic function. Diastolic responders decreased from 29% to 10% of patients, and systolic responders from 76% to 48%, in the best versus the worst lead position, respectively. Improvements in diastolic function were less pronounced than in systolic function (relative change −14% vs +28%, P < 0.05). Overall, 45% were both systolic and diastolic responders, 17% were both systolic and diastolic nonresponders, and 38% had opposite responses .
Conclusions : Changes in systolic and diastolic function were both highly dependent on the LV stimulation site. Diastolic function was less influenced by CRT and a high proportion of patients had discordant results.     

Efficacy and Safety of Rate Responsive Pacing in Patients with Coronary Artery Disease and Angina Pectoris

The present study included 17 patients with angina pectoris and coronary artery disease in whom a rate responsive ventricular pacemaker (Medtronic Activitrax) had been implanted. All patients had an exclusively paced rhythm. Single blinded, random, cross-over treadmill tests in the rate responsive pacing mode (VVIR) and in the fixed-rate demand mode (VVI) were performed, with an interval of 4-6 weeks. Mean exercise duration increased by 25% during VVIR pacing. Maximal heart rate increased significantly during VVIR compared to VVI pacing (VVI = 74 +/- 2 bpm, VVIR = 116 +/- 8 bpm, P less than 0.001) as did the rate-pressure product (VVI = 10.850 +/- 1,124, VVIR = 16.628 +/- 2,110, P less than 0.001). Despite improved performance, the number of anginal attacks per week and the nitroglycerin consumption did not show a significant difference between the two pacing modes. It is concluded that rate responsive pacing is beneficial and safe in patients with angina pectoris and coronary artery disease.     

SUPERFICIAL BLADDER TUMORS AND INCREASED REACTIVITY AGAINST MYCOBACTERIAL ANTIGENS BEFORE BACILLUS CALMETTE-GUERIN THERAPY

Purpose

The precise mechanism of action of bacillus Calmette-Guerin (BCG) in bladder cancer treatment remains poorly understood. Whether bladder tumor cells are destroyed by nonspecific mechanisms or targeted by specifically activated lymphocytes recognizing cognate antigens is unclear. To investigate a possible cross-reactivity between BCG and bladder cell tumors, we tested before BCG treatment the lymphoproliferation of peripheral blood lymphocytes against several mycobacterial antigens, including the secreted fibronectin binding antigen 85 complex from BCG (AG 85) in patients with superficial bladder tumors compared to control matched patients.

Materials and Methods

Using a whole blood assay, T cell response against purified protein derivative, BCG extract, whole BCG, purified AG 85, and the nonspecific mitogens pokeweed and phytohemagglutinin was investigated in 79 patients with superficial bladder tumors before BCG and in 39 control subjects without malignancy matched for age and sex. Neither group had a history of tuberculosis. Lymphoproliferation was measured with a tritiated thymidine uptake assay on day 7 of culture.

Results

Of the 79 patients with superficial transitional cell carcinoma, a significant lymphoproliferative response before BCG against PPD, BCG extract, whole BCG and AG 85 was observed in 65 (82.2%), 67 (84.81%), 30 (37.97%) and 49 (62.02%) patients, respectively. Of the 39 controls only 26 (64.1%), 23 (58.9%), 3 (7.7%) and 3 (7.7%) patients, respectively, had a significant lymphoproliferation against PPD, BCG extract, BCG and AG 85 (p >0.05, p = 0.004, p = 0.00001 and p = 0.00001, respectively). In terms of lymphoproliferative levels, patients with superficial transitional cell carcinoma also showed a significantly higher response against PPD (p = 0.000012), BCG extract (p = 0.000001), AG 85 (p = 0.000001), whole BCG (p = 0.00001) and pokeweed (p = 0.01) than controls but not against phytohemagglutinin.

Conclusions

Patients with superficial transitional cell carcinoma demonstrate an increased lymphoproliferation against mycobacterial antigens before BCG compared to control subjects. Although a nonspecific activation of the immune system cannot be excluded at this stage, our data may suggest the possible existence of bladder cancer antigens cross-reactive with mycobacterial antigens responsible for boosting precursor cells witnessing previous contacts with mycobacteria. The implication of these findings in the antitumoral mechanism of action of BCG are under investigation.     

Unusual Approach of a Pacemaker Electrode in a Patient with a Silent Superior Vena Cava Syndrome

A man with a history of bilateral pectoral pocket infection and subsequent pacemaker implantation with a screw-in epicardial lead was referred because of increasing lead impedance. Venography revealed bilateral total occlusion of the subclavian and innominate veins with extensive collateral formation in this asymptomatic patient. Both internal jugular veins were also totally occluded. Because repeated pacemaker implantation using epicardial leads resulted in increasing lead impedance of the ventricular lead within 1 year after implant, an alternative approach was found using the superior caval vein with minimal invasive thoracotomy for single lead VDD pacing.     

Usefulness of Echocardiography to Predict Inappropriate Atrial Sensing in Single-Lead VDD Pacing

Reliable atrial sensing is the prerequisite for restoration of atrioventricular synchrony in patients with single-lead VDD pacing systems. To determine echocardiographic variables associated with inappropriate atrial sensing, 21 consecutive patients with symptomatic second- or third-degree AV block and normal sinus node function were studied. Prior to implantation echocardiographic measurements of end-systolic and end-diastolic dimensions and volumes of the right atrium and right ventricle were performed. All patients underwent implantation of a Medtronic Thera VDD(d) pacemaker with a bipolar Medtronic Capsure electrode. A minimal amplitude of the unfiltered atrial electrocardiogram of > or =0.5 mV was required for permanent lead position and the atrial sensitivity was programmed below the lowest recorded value. Appropriate atrial sensing (atrial triggered ventricular paced complexes/total number of ventricular paced complexes) was assessed during 24-hour Holter monitoring and treadmill exercise testing 3 to 6 weeks after implantation. Inappropriate atrial sensing (<95% correct atrial synchronization during Holter registration and/or <97.5% during exercise testing) was present in nine patients. Right atrial volumes and the right ventricular end-diastolic volume was significantly higher, as compared to patients without inappropriate sensing (12 patients). The right atrial and diastolic volumes had the highest correlation with correct atrial sensing r = 0.83, P<0.0001). Using a postdefined cut-off value of > or =80 mL for the end-diastolic right atrial volume, sensitivity and specificity for inappropriate sensing was 100% and 92%, respectively. These findings show that preimplant echocardiography can identify patients with inappropriate sensing during VDD pacing, in whom DDD pacing should be considered.     

The Effect of Rate Responsive Pacing in Patients with Angina Pectoris on the Extent of Ischemia on 201-Thallium Exercise Scintigraphy

VAN CAMPEN, L.C.M.C., et al. : The Effect of Rate Responsive Pacing in Patients with Angina Pectoris on the Extent of Ischemia on 201-Thallium Exercise Scintigraphy. In patients with coronary artery disease (CAD), rate responsive pacing is considered to be contraindicated because an increase in heart rate may increase oxygen demand. Although previous studies have shown no subjective increase in ischemia during rate responsive pacing, data from objective assessment have not been documented. The goal of this study was to determine if there was an increase in ischemia on 201-Thallium (²⁰¹TI) exercise scintigraphy in this mode of pacing in patients with CAD and angina. Eighteen consecutive patients with chronic atrial fibrillation and symptomatic bradyarrhythmias with a pacemaker for more than 6 months participated in the study. In VVI and VVIR modes a symptom-limited exercise ²⁰¹TI scintigram was performed in a single blind randomized crossover fashion. Exercise duration, anginal attacks, use of nitroglycerine (NTG) tablets, blood pressure, and analysis of the scintigrams were assessed during each pacing mode. Fifteen men and three women were included (  age 65.9 ± 4.9 years, LVEF 0.44 ± 0.07  ). Four were in Class III angina pectoris, and 14 in class II. The mean exercise duration increased 28% in the VVIR group without an increase in anginal attacks per week or the use of NTG tablets. On scintigrams, no differences were seen between the two groups. One patient was withdrawn from the study because of an increase in angina pectoris (AP) attacks during VVIR pacing. Rate responsive pacing is safe and effective in patients with CAD without an increase in subjective and objective signs of ischemia.