Novel oral anticoagulants for the prevention of thromboembolism in patients with atrial fibrillation.

The most significant complication of atrial fibrillation (AF) is thromboembolic stroke. Furthermore, the consequences of AF-related stroke tend to be more severe than those of other aetiologies. The need for safe, effective and convenient anticoagulation is clear. Warfarin is the current mainstay of treatment but its prescription and use remains sub-optimal, despite clear evidence and guidance to support its use. Many patients taking warfarin spend a significant amount of time subtherapeutically anticoagulated and the requirement for regular monitoring of warfarin's anticoagulant activity is both inconvenient and costly. Novel oral anticoagulants promise more predictable and convenient anticoagulation. They have potential superiority over warfarin for preventing thromboembolic stroke and appear to be associated with fewer haemorrhagic effects. Understanding the important background to the novel agents presents an opportunity to tailor anticoagulant treatment to the individual. This should allow a greater proportion of the eligible population access to effective anticoagulation. Furthermore, it should reduce their exposure to the risk of both thromboembolic and haemorrhagic stroke and their potentially devastating consequences.

The simultaneous use of a biventricular implantable cardioverter defibrillator (ICD) and transcutaneous electrical nerve stimulation (TENS) unit: implications for device interaction.

Undesirable sensing of external sources of electromagnetic interference by ICDs is well known. A transcutaneous electrical nerve stimulation (TENS) device has been reported to interfere with an ICD resulting in an inappropriate shock and patients with implanted defibrillators or pacemakers have been cautioned about the use of such units to treat chronic pain. We describe a patient regularly using TENS therapy for pain who subsequently received a biventricular ICD for malignant ventricular arrhythmias and medically refractory cardiac failure. He underwent testing for device interaction immediately post-implant. This did not show inappropriate sensing by either ICD or pacemaker component of his heart failure device. However, six months later, the patient complained of dizziness and bradycardia with application of TENS. Further testing did reveal interference with pacemaker function. Thus, even if initial testing is negative and reassuring, patients with a biventricular ICD still require careful follow-up for potential interaction and should be cautioned against the use of TENS, especially if they are pacemaker-dependent.

Long-term survival after permanent pacemaker implantation: analysis of predictors for increased mortality.

AIMS: To determine long-term time-related survival and evaluate risk factors for increased mortality in patients following their first permanent pacemaker implantation. METHODS AND RESULTS: Analysis of patient records from implant to follow-up. Patient-specific time-lines were constructed to date of last review or death. Observed survival was estimated by event-free analysis using the Kaplan-Meier method. Expected survival was derived from age- and gender-matched cohorts. Risk factors for mortality were sought using the multivariate Cox proportional hazards method and risk ratios estimated. Eight hundred and thirty-three patients underwent implantation of their first permanent pacemaker from April 1992 to January 1994, and were locally followed up. Survival data were available for 803 (96.4%) patients (median age, 77.3 years [5th to 95th centile range: 53.5 to 89 5 years]) and follow-up was complete in 94.8%. At implant. dual-chamber systems were implanted in 443 (55.1%). single-chamber ventricular systems in 321 (40.0%), and single-chamber-atrial systems in 39 (4.9%). Observed survival after implantation was significantly worse than expected (P<0.001). Independent predictors of increased mortality were: age at implant (risk ratio [RR] 1.06: 95% confidence interval [CI] 1.01 to 1.12). VVI pacing mode (RR 1.64; 95% CI 1.34 to 1.93), cardiomyopathy (RR 5.86; 95% CI 4.86 to 6.86), male gender (RR 1.27; 95% CI 1.22 to 1 32) and valvular heart disease (RR 2.01: 95% CI 1.98 to 2.04). CONCLUSIONS: At the end of follow-up, mortality was much higher than expected. In this typical pacemaker population. age at implant and VVI pacing mode were independently associated with increased mortality with accompanying heart disease having the greatest individual impact.

Continuous ambulatory monitoring of absolute right ventricular pressure and mixed venous oxygen saturation in patients with heart failure using an implantable haemodynamic monitor: results of a 1 year multicentre feasibility study.

BACKGROUND: Implantable sensors that monitor haemodynamics over time may be useful in patients with heart failure. This multicentre study assessed the feasibility of a system that has one sensor measuring absolute pressure and another measuring mixed venous oxygen saturation (SvO(2)). Both sensors were mounted on leads that were implanted in the right ventricle. METHODS: Twenty-one patients with heart failure (NYHA II-III) were included. Comparisons were made to right heart catheterizations at implant and at 2, 6 and 12 months thereafter. Patients underwent several haemodynamic provocations during the catheterizations. RESULTS: Overall, among functioning sensors, the IHM-1 values were highly correlated with reference values for all time points during all provocations, demonstrating high reproducibility and stability (r(2)=0.91, 0.79 and 0.78 for systolic, right ventricular diastolic and SvO(2), respectively). Although IHM-1 underestimated reference pressure values by 4.5 mmHg and SvO(2)by 1.6%, this difference was consistent across provocation and stable over 12 months of follow-up. Twelve of the 21 oxygen sensors failed to function and two pressure sensors had component failures. Preliminary analysis of long-term data revealed haemodynamic patterns that may be key indicators for therapeutic interventions. CONCLUSION: This multicentre feasibility study demonstrated the accuracy and stability of sensors implanted in the right ventricle. The IHM-1, using right ventricular pressures and SvO(2), with improved performance, might be useful in the study of pathophysiological mechanisms and treatment interventions in heart failure.

Single chamber atrial pacing: an underused and cost-effective pacing modality in sinus node disease.

OBJECTIVE: To determine the safety and cost effectiveness of single chamber atrial pacing in patients with sinus node disease. DESIGN: Retrospective follow up study. SETTING: Tertiary referral centre. PATIENTS: 81 patients with single chamber atrial pacemakers implanted between 1992 and 1996. MAIN OUTCOME MEASURES: The development of high grade atrioventricular block resulting in a further pacemaker procedure. The cost savings of changing our current pacing practice to conform with British Pacing and Electrophysiology Group guidelines. RESULTS: During the follow up period, four patients (5.8%) required a further procedure to upgrade their atrial pacemaker to a dual chamber system owing to the development of high grade atrioventricular block. In 1995 and 1996, 343 pacemakers were implanted in patients with sinus node disease; 19 (5.5%) received single chamber atrial pacemakers and 271 (79%) dual chamber pacemakers. If the current pacing practice was changed so that all patients received single chamber atrial pacemakers, with revision for symptomatic atrioventricular block, savings in excess of 206,000 Pounds would have been made in the two year period. CONCLUSIONS: Atrial pacing in patients with sinus node disease is underused. The need for patients to undergo further procedures owing to the development of atrioventricular block is small and significant cost savings could be made by changing pacemaker practice.

Atrial pacing leads following open heart surgery: active or passive fixation?

The right atrial appendage is often amputated at the time of cardiopulmonary bypass. Because of concerns regarding lead displacement, use of active fixation atrial leads has been recommended in patients who require permanent atrial or dual chamber pacing after open heart surgery. We evaluated the acute and chronic performance of active and passive fixation atrial leads implanted at our institution between 1985 and 1993 in patients with previous open heart surgery. Of 78 consecutive patients, 38 had an active fixation atrial lead, 28 had a passive fixation steroid-eluting lead, and 12 had a passive fixation lead without steroid-eluting properties. At implantation, sensed P wave amplitudes were similar in the three groups, but lead impedance and threshold were significantly higher for active fixation leads compared to all passive fixation leads. During follow-up, atrial pacing thresholds were significantly higher, and sensed P wave amplitudes significantly lower, in the patients with active fixation leads compared to those with passive fixation leads. Loss of sensing occurred in 6 of 38 (16%) patients with active fixation leads and 1 of 40 (2.5%) patients with a passive fixation lead (P = 0.027). Atrial lead displacement occurred in two patients with active fixation leads and one with a passive fixation lead. Comparison with a parallel group of patients without previous open heart surgery demonstrated that atrial lead performance was similar in the two groups. We conclude that, when permanent atrial or dual chamber pacing is necessary in patients with prior open heart surgery, it is appropriate to implant a passive fixation atrial lead except on the infrequent occasions when a stable atrial position cannot be obtained.

Cost savings with nonthoracotomy implantable cardioverter-defibrillators.

We analyzed hospital and physician charges for 99 consecutive patients who underwent implantable cardioverter-defibrillator (ICD) implantation at our institution. Eighteen patients received an epicardial lead system and 81 were scheduled to receive a nonthoracotomy lead system, the generator being implanted either abdominally (n = 62) or pectorally (n = 19). The epicardial group had a significantly longer convalescent stay (11.6 +/- 2.5 days; mean +/- SEM) than the abdominal nonthoracotomy group, analyzed by intention to treat (4.6 +/- 0.5 days) or by treatment received (3.8 +/- 0.2 days; p <0.0001). Postoperative stay for the pectoral group was shorter still (2.9 +/- 0.4 days; p <0.033). Total charges for the epicardial group were $99,081 +/- $25,094, significantly higher than those for any of the nonthoracotomy groups (p <0.017). Total charges for the pectoral group were $44,128 +/- $2,465, significantly less than those for the abdominal nonthoracotomy group, analyzed by intention to treat ($59,961 +/- $1,369; p <0.05) or by treatment received ($56,679 +/- $635; p <0.05). Cost reductions in the nonthoracotomy groups were primarily due to decreased in-hospital convalescence period, lower surgeon and anesthesiologist fees, and lower procedure-day hospital charges in the pectoral group. The use of ICDs with nonthoracotomy leads can result in significantly shorter in-hospital convalescence and a reduction in total implant-related charges of 40% to 55%. The use of pectorally implanted ICDs results in further reduction in hospital stay and further cost reduction of 22% to 26%. The trend toward shorter convalescent stay without postimplant testing is likely to reduce further the overall costs of ICD implantation.

Trends in pacemaker mode prescription 1984-1994: a single centre study of 3710 patients.

OBJECTIVE: To evaluate trends in pacemaker mode prescription from 1984 to 1994 with particular reference to the changes in pacemaker mode prescription for patients aged 80 years and older at implant. DESIGN: Prospective evaluation of indications for pacing and pacemaker mode prescription in all patients undergoing new pacemaker implantation from 1992 to 1994. Comparison with retrospectively obtained data for patients paced from 1984 to 1991. SETTING: Tertiary referral cardiothoracic centre. PATIENTS: Group 1: 2622 patients paced at one centre and entered into the national pacing database from 1984 to 1991. Group 2: 1088 consecutive patients paced from 1992 to 1994. RESULTS: Use of atrial (AAI) and dual chamber (DDD) pacemakers increased progressively in patients of all ages from 1984 to 1994. There was an increase in the proportion of patients aged 80 years and older from 25.4% (group 1) to 40.5% (group 2). Patients of all ages in group 2 were more likely to receive DDD units for atrioventricular block (odds ratio (95% confidence interval) (CI) 9.0 (7.0 to 11.5)) and AAI or DDD units for sinus node disease (odds ratio (95% CI) 11.0 (7.7 to 15.8)) than those in group 1. Elderly patients (age > or = 80 at implant) with atrioventricular block or sinus node disease and a suitable atrial rhythm were less likely to receive DDD or AAI pacemakers than younger patients in both groups. CONCLUSIONS: Use of atrial and dual chamber pacing modes has increased substantially in patients of all ages over the last decade. Although elderly patients represent an increasing proportion of the paced population, they remain less likely to receive atrial or dual chamber pacemakers than younger patients.

Early complications of permanent pacemaker implantation: no difference between dual and single chamber systems.

OBJECTIVE: To evaluate the incidence of intraoperative and early postoperative complications (up to two months after implant) of endocardial permanent pacemaker insertion in all patients under-going a first implant at a referral centre. METHODS: Prospective evaluation of all endocardial pacemaker implantation procedures performed from April 1992 to January 1994 carried out by completion of standard audit form at implant. Patients' demographic data, medical history, details of pacemaker hardware used, and any complications were noted. Follow up information was also collected prospectively onto standard forms at pacemaker outpatient clinic. SETTING: United Kingdom tertiary referral cardiothoracic centre. PATIENTS: 1088 consecutive patients underwent implantation of their first endocardial permanent pacemaker from April 1992 to January 1994. Implant and follow up data were available for 1059 (97.3%) patients at analysis. The median (range) age was 77 years (16-99); 51.2 % were male. RESULTS: Dual chamber units were implanted in 54.1% of patients, single chamber atrial in 5.2%, and ventricular in 40.7%. A temporary pacing lead was present at implant in 22.9% of patients. Most (93.6%) implants were performed via the subclavian vein. Immediate complications were rare: eight (0.8%) patients developed pneumothorax requiring medical treatment and 11 (1.0%) an insignificant pneumothorax. There was no significant difference in the pneumothorax rate for dual chamber (DDD) compared with single chamber systems. Arterial puncture without sequelae was documented in 2.7% of attempts at subclavian vein cannulation. A total of 35 patients (3.3%) required reoperation; the reoperation rate for dual chamber (3.5%) was similar to that for single chamber (3.1%) systems. Electrode displacement (n = 15, 1.4%) was the most common reason for reoperation. Atrial lead displacement (n = 10, 1.6% of atrial leads) was significantly more common than ventricular lead displacement (n = 5, 0.5% of ventricular leads, P = 0.047). There was no difference in electrode displacement rates for dual (1.6%) compared with single (1.2%) chamber systems. Pacemaker pocket infection led to reoperation in 10 patients (six dual, four single chamber, P = not significant) and was significantly more common in patients who had a temporary pacing lead in place at implant (2.9%) than in those who did not (0.4%, P = 0.0014). Five patients (0.5%) required reoperation for generator erosion (two dual, three single chamber, P = not significant). and a further five for drainage of haematoma or a serous fluid collection (three dual, two single chamber, P = not significant). Complications that did not require reoperation were also rare. Undersensing occurred in 10 patients (0.9%). Atrial undersensing (n = 8) was significantly more common than ventricular undersensing (n = 2, P = 0.017). All patients were successfully treated by reprogramming of sensitivity. Superficial wound infection was treated successfully with antibiotics in nine patients (six dual, three single chamber, P = not significant). Three patients with DDD generators developed sustained atrial fibrillation: two required reprogramming to VVI mode and one required cardioversion. CONCLUSIONS: Permanent pacing in a large tertiary referral centre with experienced operators carries a low risk. Infection rates are low, < 1% overall but significantly higher in patients who undergo temporary pacing before implantation. Lead displacement and undersensing are more likely to occur with atrial than ventricular leads. The overall complication rate for dual chamber pacing, however, is no higher than for single chamber pacing.

Stability of the DDD pacing mode in patients 80 years of age and older.

We reviewed the records of 119 consecutive patients aged 80 years or older (mean age 84 +/- 3.7 years) in whom a dual chamber pacemaker was implanted between 1984 and 1991. Follow-up data was available up to February 1993. Immediate postimplantation complications were rare. Nine patients were lost to follow-up, all within 6 months of implantation. An additional seven patients died within 6 months of implantation. Long-term follow up for at least 6 months from implantation was available for 103 of the 119 patients (87%). Of these 89 (86%) remained in functioning DDD mode for a mean of 22 +/- 15 months from implantation. Nine patients were reprogrammed to VVI mode, six due to atrial fibrillation and three due to failure of atrial sensing or pacing. One patient was programmed DVI for failure of atrial sensing; 94 of 112 patients (84%) whose status was definitely known in February 1993 remained in functioning DDD mode until death or last follow-up. Cumulative survival in DDD mode was 78% at 30 months. We conclude that DDD pacing is stable in the great majority of patients in their ninth and tenth decades who present with rhythms amenable to dual chamber pacing and who have no history of sustained atrial fibrillation.

Initial experience with a new single chamber, dual sensor rate responsive pacemaker. The Topaz Study Group.

In August 1991, a new single chamber pacemaker became available that utilizes information from two sensors, activity and stimulus-to-T wave (QT) interval. We are reporting on the first 90 implants in 21 centers. T wave sensing was adequate at implantation in 88/90 patients, with a safety margin of > 100% in 86/90. Activity sensing was adequate in all patients. The contribution of each sensor (sensor blending) is programmable for each patient. Of 75 patients assessed at 1 month after implant, three have been programmed to "Activity-Only" mode, and 72 to dual sensor mode. Of these, 18 have been programmed to "QT < Activity," 48 to "QT = Activity," and 6 to "QT > Activity." Forty-five patients underwent exercise testing in dual sensor mode and a subgroup of 15 also underwent exercise testing in Activity-Only mode. The dual sensor mode produced a more gradual increase in pacing rate. Sensor Cross Checking satisfactorily prevented a sustained high pacing rate in tests of false-positive activity sensing (tapping, vibrating pacemaker, or static pressure). The maximum pacing rate on walking downstairs (94.2 +/- 7.2 ppm) was similar to that produced by walking upstairs (91.6 +/- 5.9 ppm). We conclude that initial assessment of this dual sensor, single chamber, rate responsive pacemaker confirms that the algorithm for combining data from two sensors functions satisfactorily. Dual sensor rate responsive pacing may offer significant advantages over single sensor devices, and further studies of this novel device are indicated.

Early treatment with captopril after acute myocardial infarction.

OBJECTIVES: To determine the effects of early treatment with captopril on haemodynamic function, neuroendocrine biochemistry, left ventricular structure, clinical outcome, and exercise capacity over one year from acute myocardial infarction. DESIGN: Randomised, double blind, placebo controlled comparison of captopril and placebo. SETTING: Coronary care units and cardiology departments of two university teaching hospitals in Glasgow. PATIENTS: 99 haemodynamically stable patients with acute myocardial infarction, selected on clinical grounds as being at risk of late ventricular dilatation. INTERVENTION: Captopril or identical placebo started between six and 24 hours after start of symptoms and continued for 12 months. Target maintenance dose was 25 mg three times a day. MAIN OUTCOME MEASURES: (a) Acute haemodynamic effects of treatment; (b) neuroendocrine biochemistry from admission to two months; and (c) change in echocardiographic measures of left ventricular size, clinical outcome, and exercise capacity after 12 months of treatment with a separate analysis of the effects of one month of treatment withdrawal on left ventricular volumes. RESULTS: Captopril caused acute reductions in mean (SEM) pulmonary artery pressure (2.48 (0.69) mm Hg) and systemic vascular resistance (260 (103)) dyn.s.cm-5). Over the first 10 hours captopril reduced mean arterial pressure by 12.1 (2.4) mm Hg compared with 3.8 (1.9) mm Hg in the placebo group. No patient had to be withdrawn from the captopril group because of hypotension. From day 1 onwards systolic and diastolic arterial pressures in the captopril treated group were slightly but not significantly lower than on placebo. There was no difference in the incidence of ventricular or supraventricular arrhythmia with treatment. Captopril prevented the day 3 peak in angiotensin II that occurred in the placebo group (peak concentration (interquartile range): 10.1 (4.8-19.4) pg/ml v 16.8 (4.3-46.3) pg/ml)) but had no effect on atrial natriuretic factor, arginine vasopressin, or catecholamines. Plasma atrial natriuretic factor remained above normal in both groups at two months after infarction. After one year left ventricular volume indices had increased less on captopril than on placebo: left ventricular end systolic volume index 5.4 ml/m2 v 14.7 ml/m2 (95% confidence interval (95% CI) of difference -14.6 to -3.9; p = 0.0011); left ventricular end diastolic volume index 8.4 ml/m2 v 19.0 ml/m2 (95% CI of difference, -17.0 to -4.2; p = 0.0016). Withdrawal of captopril for one month did not affect ventricular volumes. There was no difference in exercise capacity. CONCLUSIONS: Captopril started between six and 24 hours after acute myocardial infarction is not associated with significant hypotension. It suppresses activation of the renin angiotensin system but has no effect on plasma concentrations of other neurohormones. Atrial natriuretic factor remains raised at two months after myocardial infarction. Captopril significantly decreases left ventricular dilatation. This effect is not lost after one month of treatment withdrawal and is thus due to an alteration of left ventricular structure and not to a short lived haemodynamic action of captopril. Long-term treatment with captopril does not result in improved aerobic exercise capacity after acute myocardial infarction.

Long-term follow up of patients treated with a software based antitachycardia pacemaker.

INTRODUCTION: Over the past decade, several advances have been made in the management of tachycardias by pacing techniques, but limited data are available on the long-term outcome of patients treated with antitachycardia pacemakers. PATIENTS AND METHODS: An antitachycardia pacemaker, the Intermedics Intertach, was implanted in 22 (17 female) patients with supraventricular tachycardia over a five year period. All were selected after detailed evaluation and testing of a temporary antitachycardia pacemaker system showed that their arrhythmia could be stopped promptly, reliably, and under different physiological conditions. RESULTS: The 22 patients have been followed up for a mean period of 57.3 (range 19-76) months. All except one of the patients has had frequent episodes of tachycardia reliably ended by the pacemaker. Complications have occurred in seven patients, necessitating removal of the pacing system in four. Of the 18 patients who continue to have pacemakers, seven are being treated with beta blockers or verapamil; no other antiarrhythmic drugs are being taken. CONCLUSIONS: Antitachycardia pacing is an acceptable long-term option for carefully selected patients with supraventricular tachycardia, but even after extensive testing a substantial number of the patients may continue to require drug treatment. Furthermore, the widespread use of curative techniques for supraventricular arrhythmias (catheter ablation and surgery) has decreased the need for this palliative treatment.

Rate-responsive pacing using electrographic parameters as sensors.

The use of evoked QT-interval and ventricular depolarization gradient as sensors for rate-responsive pacing is described in this article. The QT interval has been used as a biosensor in implantable pacemakers since 1981, and recent refinements have improved the rate response characteristics and simplified the programming of this pacemaker. Recently, QT and activity sensing have been combined to produce a dual-sensor rate-responsive pacemaker that may offer advantages over single-sensor devices. The ventricular depolarization gradient has been incorporated into a closed-loop rate-responsive pacing system and is undergoing clinical evaluation.