Remote-only monitoring for patients with cardiac implantable electronic devices: a before-and-after pilot study.

BACKGROUND: Outcomes for patients with cardiac implantable electronic devices are better when follow-up incorporates remote monitoring technology in addition to in-clinic visits. For patients with implantable devices, we sought to determine the feasibility, safety and associated health care utilization of remote-only follow-up, along with its effects on patients' quality of life and costs. METHODS: This multicentre before-and-after pilot study involved patients with new or existing pacemakers or implantable cardioverter defibrillators. The "before" phase of the study spanned the period October 2015 to February 2017; the "after" phase spanned the period October 2016 to February 2018. The exposure was remote-only follow-up in combination with Remote View, a service that facilitates access to device data, allowing device settings to be viewed remotely to facilitate remote programming. Outcomes at 12 months were feasibility (adherence to remote monitoring), safety (rate of adverse events) and health care utilization (remote and in-clinic appointments). We also assessed quality of life, using 3 validated scales, and costs, taking into account both health care system and patient costs. RESULTS: A total of 176 patients were enrolled. Adherence (defined as at least 1 successful remote transmission during follow-up) was 87% over a mean follow-up of 11.7 (standard deviation 2.2) months. There was a reduction in in-clinic visits at specialized sites among patients with both implantable defibrillators (26 v. 5, p < 0.001, n = 48) and pacemakers (42 v. 10, p < 0.001, n = 51). There was no significant change in visits to community sites for patients with defibrillators (13 v. 17, p = 0.3, n = 48). The composite rate of death, stroke, cardiovascular hospitalization and device-related hospitalization was 7% (n = 164). No adverse events were linked to the intervention. There was no change in quality-of-life scales between baseline and 12 months. Health care costs were reduced by 31% for patients with defibrillators and by 44% for those with pacemakers. INTERPRETATION: This pilot study showed the feasibility of remote-only follow-up, with no increase in adverse clinical outcomes and no effect on quality of life, but with reductions in costs and health care utilization. These results support progression to a larger-scale study of whether superior effectiveness and reduced cost can be achieved, with preservation of safety, through use of remote-only follow-up. TRIAL REGISTRATION: ClinicalTrials.gov, no. NCT02585817.

Evidence for reduced susceptibility to cardiac bradycardias in South Asians compared with Caucasians.

OBJECTIVES: To investigate ethnic differences in susceptibility to bradycardias in South Asian and white European patients in the UK by determining rates of permanent pacemaker (PPM) implantation for sinus node dysfunction (SND) and atrioventricular block (AVB) in each ethnic group. METHODS: We carried out a retrospective cohort study into new PPM implantation during the period from 1 May 2006 to 31 March 2014, in patients of South Asian and Caucasian ethnicity resident in Leicestershire, UK. Numbers of individuals at risk in each ethnic group were derived from UK National Census data of 2011. Crude, and age-standardised incidence rates and risk ratios per 1000 population of PPM implantation were calculated for Caucasians and South Asians. RESULTS: During the study period, 4883 individuals from the Leicestershire population of 980 328 underwent PPM implantation, a cumulative implantation rate of 4.98/1000 population. The population cumulative PPM implantation rate for SND was 1.74/1000, AVB 2.83/1000 and other indications 0.38/1000 population. The crude incidence in Caucasians (6.15/1000 population) was higher than in South Asians (1.07/1000 population) and remained higher after age standardisation (5.60/1000 vs 2.03/1000, P<0.001). The age-standardised cumulative PPM implantation rates were lower in South Asians for both SND (0.53/1000 in South Asians; 1.97/1000 in Caucasians, P<0.001) and AVB (1.30/1000 in South Asians; 3.17/1000 in Caucasians, P<0.001). Standardised risk ratios (95% CI) for PPM implantation in South Asians compared with Caucasians for all pacing indications, SND and AVB were 0.36 (95% CI 0.36 to 0.37), 0.27 (95% CI 0.27 to 0.28) and 0.41 (95% CI 0.41 to 0.42), respectively. CONCLUSIONS: Rates of PPM implantation are lower in South Asians residing in the UK, compared with Caucasians. This observation raises the possibility of lower inherent susceptibility to bradycardias in South Asians compared with Caucasians. Studies aimed at identifying underlying mechanisms, including possible genetic differences, are warranted.

The development of AF over time in patients with permanent pacemakers: objective assessment with pacemaker diagnostics demonstrates distinct patterns of AF.

AIMS: To describe the long-term patterns of atrial fibrillation (AF) in patients with permanent pacemakers. METHODS AND RESULTS: A total of 2092 pacemaker Holter downloads were analysed in 323 patients with dual chamber permanent pacemakers, describing a cumulative 1031 patient-years of beat-to-beat monitoring. Four subtypes of AF were applied: (i) non-progressive low-burden PAF (NPLB-PAF, n = 120): such patients never have >1% AF burden throughout follow-up; (ii) chronic progressive PAF (CP-PAF, n = 55): AF burden increases but is never 100%; (iii) relapsing-remitting PAF (RR-PAF, n = 78): AF burden has reduced at least once by more than 2% and is never 100%; (iv) persistent AF (PersAF, n = 70): 100% AF burden for at least 28 days. Overall, mean AF burden rose 0.34% per year (P < 0.0001). After accounting for age, heart failure (HF) had a significant interaction with AF burden (P = 0.0022), but HATCH score and CVA/TIA did not. There were no differences in the frequency or duration of monitoring between the four AF subtypes. Atrial fibrillation episode frequency discriminated between subtypes (P = 0.0004). Eighteen of 70 (26%) patients with PersAF had pacemaker documented episodes of sinus rhythm (i.e. reversion to 'paroxysmal AF') after the onset of PersAF. CONCLUSION: In this cohort, the development of AF over time appears more complex than current definitions suggest. Atrial fibrillation can remain low burden without progression, remit-relapse, or progress as is described in currently accepted definitions. More frequent episodes of AF indicated a favourable subtype. Persistent AF is not inevitable, and can revert to paroxysmal AF. CLINICAL TRIAL REGISTRATION: NCT02016950, http://clinicaltrials.gov/show/NCT02016950.

Trends in permanent pacemaker implantation in the United States from 1993 to 2009: increasing complexity of patients and procedures.

OBJECTIVES: This study sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. BACKGROUND: The Medicare National Coverage Determination for permanent pacemaker, which emphasized single-chamber pacing, has not changed significantly since 1985. We sought to define contemporary trends in permanent pacemaker use by analyzing a large national database. METHODS: We queried the Nationwide Inpatient Sample to identify permanent pacemaker implants between 1993 and 2009 using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes for dual-chamber (DDD), single-ventricular (VVI), single-atrial (AAI), or biventricular (BiV) devices. Annual permanent pacemaker implantation rates and patient demographics were analyzed. RESULTS: Between 1993 and 2009, 2.9 million patients received permanent pacemakers in the United States. Overall use increased by 55.6%. By 2009, DDD use increased from 62% to 82% (p < 0.001), whereas single-chamber ventricular pacemaker use fell from 36% to 14% (p = 0.01). Use of DDD devices was higher in urban, nonteaching hospitals (79%) compared with urban teaching hospitals (76%) and rural hospitals (72%). Patients with private insurance (83%) more commonly received DDD devices than Medicaid (79%) or Medicare (75%) recipients (p < 0.001). Patient age and Charlson comorbidity index increased over time. Hospital charges ($2011) increased 45.3%, driven by the increased cost of DDD devices. CONCLUSIONS: There is a steady growth in the use of permanent pacemakers in the United States. Although DDD device use is increasing, whereas single-chamber ventricular pacemaker use is decreasing. Patients are becoming older and have more medical comorbidities. These trends have important health care policy implications.

Automatic assessment of atrial pacing threshold in current medical practice.

AIMS: The aim of this study was to validate the ambulatory automatic atrial threshold monitoring algorithm by comparing the measurements assessed by the automatic system and those evaluated manually by the physician at discharge, 2- and 8-month follow-up sessions. METHODS AND RESULTS: This is an observational multicentric prospective study of 352 patients implanted with EnPulse(®) DR pacemakers. Mean age was 76.3 ± 9.4 years. Indications of pacing were atrio-ventricular block (AVB) (64%) and sinus dysfunction (SD) or brady-tachy syndrome (36%). The automatic atrial threshold monitoring function was maintained at nominal programming state with daily measurement scheduled at 1:00 am. Ambulatory automatic atrial threshold assessment was possible for 91.5% of patients at discharge, 97.3% at 2 months, and 95.7% at 8 months. Causes of the unsuccessful attempts to perform automatic atrial threshold were atrial arrhythmias or permanent atrial and ventricular pacing. Feasibility is significantly better for AVB indication than SD indication due to more frequent occurrence of atrial fibrillation (AF). At each stage, there is a strict correlation between the automatic measurements and those conducted manually by the physician with a P < 0.001. CONCLUSION: Feasibility of ambulatory automatic atrial threshold is good. Results of the study show excellent correlation between the two methods for atrial threshold: there is no statistical difference between manual and automatic measurements during follow-up.

The tissue velocity imaging and strain rate imaging in the assessment of interatrial electromechanical conduction in patients with sick sinus syndrome before and after pacemaker implantation.

Tissue velocity imaging (TVI) and strain rate imaging (SRI) were recently introduced to quantify myocardial mechanical activity in patients receiving cardiac resynchronization therapy. To clear whether atrial-demand-based (AAI) (R) atrial pacing can fully simulate the electromechanical conduction of physiological state and to clarify which one is more appropriate for the assessment of electromechanical activity of the heart between TVI and SRI, 30 normal subjects and 31 patients with sick sinus syndrome (SSS) before and after AAI(R) pacemaker implantation (PI) were investigated in this study. The results showed that the time intervals (ms), P-SRa assessed by SRI (not P-Va assessed by TVI) prolonged step by step from the lateral wall of the right atrium (RA), the interatrial septum (IAS) and the left atrium (LA) in normal subjects(5.01±0.62, 17.05±3.54 and 45.09±12.26, p<0.01). P-Va and P-SRa did not differ at the RA, IAS and LA in patients with SSS before PI (p>0.05), and they were significant longer than those of normal subjects (p<0.01). However, they shortened to normal levels in patients with SSS after PI and P-SRa showed again the trend of gradually prolonging from the RA, IAS to LA. At the same time, the peak velocities and the peak strain rates during atrial contraction also returned to normal values from lower levels. These data suggested that AAI(R) atrial pacing can successfully reverse the abnormal interatrial electromechanical conduction in patients with SSS, and SRI is more appropriate for the assessment of the electromechanical activity of atrial wall than TVI.

[Assessment of time to stimulate the function of the type of AAI in the distant observation in patients with sick sinus syndrome]. / Ocena czasu funkcjonowania ukladu stymulujacego typu AAI w odleglej obserwacji u chorych na zespól chorego wezla zatokowego.

UNLABELLED: For the first time in 1966 vestibular stimulation has been applied. This idea is implemented in a patient with sinus node dysfunction and normal AV conduction. The aim of the study was to evaluate the time of AAI stimulation until the first reimplantation of stimulating system and to determine the cause of it. MATERIAL AND METHODS: Work is retrospective in nature. The analysis included 251 patients who were subjected to AAI pacemaker implantation in the period from December 1988 to January 2009. The group consisted of 150 women and 101 men. The average age of patients at the time of implantation of 62.0 +/- 13.3 years (17.3 -90.2). The median follow-up was 7.6 +/- 4.8 years (maximum 20.1 years). For each patient, Wenckebach point was above 130/min. Of the 251 patients, 98 were undergoing treatment reimplantation of stimulating system. RESULTS: The median time to stimulate the function of the type of AAI was 8.69 +/- 2.4 years. The main cause was the exhaustion of the battery replacement--91.8% of cases, but sometimes less damage to the electrodes--7.1% of cases. Duration does not depend on the gender of the patient, or to his age at the time of implantation. CONCLUSIONS: The most common cause of reimplantation is battery exhausted. AAI stimulation is very effective treatment in the test group of patients.

Preferred QT correction formula for the assessment of drug-induced QT interval prolongation.

INTRODUCTION: There is debate on the optimal QT correction method to determine the degree of the drug-induced QT interval prolongation in relation to heart rate (DeltaQTc). METHODS: Forty-one patients (71 +/- 10 years) without significant heart disease who had baseline normal QT interval with narrow QRS complexes and had been implanted with dual-chamber pacemakers were subsequently started on antiarrhythmic drug therapy. The QTc formulas of Bazett, Fridericia, Framingham, Hodges, and Nomogram were applied to assess the effect of heart rate (baseline, atrial pacing at 60 beats/min, 80 beats/min, and 100 beats/min) on the derived DeltaQTc (QTc before and during antiarrhythmic therapy). RESULTS: Drug treatment reduced the heart rate (P < 0.001) and increased the QT interval (P < 0.001). The heart rate increase shortened the QT interval (P < 0.001) and prolonged the QTc interval (P < 0.001) by the use of all correction formulas before and during antiarrhythmic therapy. All formulas gave at 60 beats/min similar DeltaQTc of 43 +/- 28 ms. At heart rates slower than 60 beats/min, the Bazett and Framingham methods provided the most underestimated DeltaQTc values (14 +/- 32 ms and 18 +/- 34 ms, respectively). At heart rates faster than 60 beats/min, the Bazett and Fridericia methods yielded the most overestimated DeltaQTc values, whereas the other 3 formulas gave similar DeltaQTc increases of 32 +/- 28 ms. CONCLUSIONS: Bazett's formula should be avoided to assess DeltaQTc at heart rates distant from 60 beats/min. The Hodges formula followed by the Nomogram method seem most appropriate in assessing DeltaQTc.

Piggy-back pacing: implantation of pacemaker and defibrillator on top of each other.

Following the publication of several landmark trials, there has been a significant increase in the cardiac device implantation. Within this population there are a number of patients who have pre-existing cardiac devices that have been placed for a number of different conditions. While the usual approach is to remove the existing unit and replace it with a new device with the removal or capping of existing lead systems, this practice often sacrifices an existing unit that still possesses good battery longevity. We explored the possibility of separating the pacing and defibrillating functions by implanting a new device on the top of the old device in a 'piggy-back fashion'. We report a series of four cases (with various indications) with differing combinations of devices. The procedure was performed safely in every one of them, and no device-device interaction was noted. Combining the new with existing units in a 'piggy-back' manner may be a safe and cost-effective technique in the selected cases.

A randomized trial comparing two different approaches of pacemaker selection.

AIMS: DDD-pacemakers are favoured in patients with sick-sinus-syndrome or AV-block. However, AAI-pacemakers for sick-sinus-syndrome or VDD-pacemakers for AV-block may provide similar benefit with lower costs. The aim is to show that a tailored approach (TA) with arrhythmia-specific pacemaker selection was equal to a standard approach (SA) regarding quality of life (QoL) at lower costs. METHODS AND RESULTS: The study was prospective and randomized with QoL as primary endpoint. Secondary endpoints were a combined endpoint of all-cause mortality, worsening heart failure or angina, atrial fibrillation (AF), stroke, these endpoints individually and costs. Of 198 patients (age 77 +/- 10 years, 43% female, ejection fraction 54 +/- 12%, follow-up 38 +/- 15 months), 94 were randomized to SA and 104 to TA. Thirty-two patients (34%) died in the SA group vs. 25 (24%) in the TA (P= ns). QoL showed no differences in all dimensions. The combined secondary endpoint was reached more frequently with SA (51%) compared to TA (37%, P = 0.045). There was no difference regarding all single secondary endpoints. Hardware costs were reduced by 15% (P < 0.0001). CONCLUSION: In long-term follow-up, a TA is equal to SA regarding the primary endpoint QoL and secondary endpoints as AF and mortality. Depending on the healthcare system, it may significantly reduce costs.

The effectiveness and cost-effectiveness of dual-chamber pacemakers compared with single-chamber pacemakers for bradycardia due to atrioventricular block or sick sinus syndrome: systematic review and economic evaluation.

OBJECTIVES: To estimate the effectiveness and cost-effectiveness of dual-chamber pacemakers versus single-chamber atrial or single-chamber ventricular pacemakers in the treatment of bradycardia due to sick sinus syndrome (SSS) or atrioventricular block (AVB). DATA SOURCES: Electronic databases and relevant Internet sites. Contact with device manufacturers and experts in the field. REVIEW METHODS: A systematic review was carried out of randomised controlled trials (RCTs). The quality of selected studies was appraised using standard frameworks. Meta-analyses, using random effects models, were carried out where appropriate. Limited exploration of heterogeneity was possible. Critical appraisal of economic evaluations was carried out using two frameworks. A decision-analytic model was developed using a Markov approach, to estimate the cost-effectiveness of dual-chamber versus ventricular or atrial pacing over 5 and 10 years as cost per quality-adjusted life-year (QALY). Uncertainty was explored using one-way and probabilistic sensitivity analyses. RESULTS: The searches retrieved a systematic review of effectiveness and cost-effectiveness published in 2002, four parallel group RCTs and 28 cross-over trials. Dual-chamber pacing was associated with lower rates of atrial fibrillation, particularly in SSS, than ventricular pacing, and prevents pacemaker syndrome. Higher rates of atrial fibrillation were seen with dual-chamber pacing than with atrial pacing. Complications occurred more frequently in dual-chamber pacemaker insertion. The cost of a dual-chamber system, over 5 years, including cost of complications and subsequent clinical events in the population, was estimated to be around 7400 pounds. The overall cost difference between single and dual systems is not large over this period: around 700 pounds more for dual-chamber devices. The cost-effectiveness of dual-chamber compared with ventricular pacing was estimated to be around 8500 pounds per QALY in AVB and 9500 pounds in SSS over 5 years, and around 5500 pounds per QALY in both populations over 10 years. Under more conservative assumptions, the cost-effectiveness of dual-chamber pacing is around 30,000 pounds per QALY. The probabilistic sensitivity analysis showed that, under the base-case assumptions, dual-chamber pacing is likely to be considered cost-effective at levels of willingness to pay that are generally considered acceptable by policy makers. In contrast, atrial pacing may be cost-effective compared with dual-chamber pacing. CONCLUSIONS: Dual-chamber pacing results in small but potentially important benefits in populations with SSS and/or AVB compared with ventricular pacemakers. Pacemaker syndrome is a crucial factor in determining cost-effectiveness; however, difficulties in standardising diagnosis and measurement of severity make it difficult to quantify. Dual-chamber pacing is in common usage in the UK. Recipients are more likely to be younger. Insufficient evidence is currently available to inform policy on specific groups who may benefit most from pacing with dual-chamber devices. Further important research is underway. Outstanding research priorities include the economic evaluation of UKPACE studies of the classification, diagnosis and utility associated with pacemaker syndrome and evidence on the effectiveness of pacemakers in children.

Cost advantage of dual-chamber versus single-chamber cardioverter-defibrillator implantation.

OBJECTIVES: The purpose of this study was to determine the least expensive strategy for device selection in patients receiving implantable cardioverter-defibrillators (ICDs). BACKGROUND: Device cost for a single-chamber ICD is less than an atrioventricular (dual-chamber) ICD (AV-ICD); however, some patients without clinical need for AV-ICD at implantation might require a later upgrade, potentially offsetting the initial cost advantage of the single-chamber device. METHODS: Decision analysis was used to estimate expected resource utilization costs of three alternative implantation strategies: 1) single-chamber device in all, with later upgrade to AV-ICD if needed; 2) initial implantation of an AV-ICD in all; and 3) targeted device selection on the basis of results of electrophysiologic testing (presence or absence of induced bradyarrhythmias or atrial arrhythmias). Clinical base estimates were obtained from retrospective review of all patients receiving ICDs between June 1997 and July 2001 at a single university hospital. Economic inputs were collected from national and single-center sources. RESULTS: In patients without other indications for electrophysiologic study (EPS), the expected per-person cost was least with the strategy of universal initial AV-ICD implantation (36,232 dollars) compared with initial single-chamber ICD/upgrade as needed (39,230 dollars) or EPS-guided selection (41,130 dollars). Sensitivity analyses demonstrated that universal AV-ICD implantation remained least expensive with upgrade rates as low as 10%. At a 5% upgrade rate, AV-ICD remained cheapest if the device cost-differential narrowed to 1,568 dollars. For patients undergoing EPS for risk assessment, EP-guided selection was least expensive. CONCLUSIONS: The strategy of universal AV-ICD implantation, which provides the benefits of dual-chamber capability while obviating any potential need for future upgrade, is the least costly strategy for most patient populations receiving ICDs.

Cost-effectiveness of dual-chamber pacing compared with ventricular pacing for sinus node dysfunction.

BACKGROUND: Compared with single-chamber ventricular pacing, dual-chamber pacing can reduce adverse events and, as a result, improve quality of life in patients paced for sick sinus syndrome. It is not clear, however, how these benefits compare with the increased cost of dual-chamber pacemakers. METHODS AND RESULTS: We used 4-year data from a 2010-patient, randomized trial to estimate the incremental cost-effectiveness of dual-chamber pacing compared with ventricular pacing and then projected these findings over the patients' lifetimes by using a Markov model that was calibrated to the first 5 years of in-trial data. To assess the stability of the findings, we performed 1000 bootstrap analyses and multiple sensitivity analyses. During the first 4 years of the trial, dual-chamber pacemakers increased quality-adjusted life expectancy by 0.013 year per subject at an incremental cost-effectiveness ratio of 53,000 dollars per quality-adjusted year of life gained. Over a lifetime, dual-chamber pacing was projected to increase quality-adjusted life expectancy by 0.14 year with an incremental cost-effectiveness ratio of approximately 6800 dollars per quality-adjusted year of life gained. In bootstrap analyses, dual-chamber pacing was cost-effective in 91.9% of simulations at a threshold of 50,000 dollars per quality-adjusted year of life and in 93.2% of simulations at a threshold of 100,000 dollars. Its cost-effectiveness ratio was also below this threshold in numerous sensitivity analyses that varied key estimates. CONCLUSIONS: For patients with sick sinus syndrome requiring pacing, dual-chamber pacing increases quality-adjusted life expectancy at a cost that is generally considered acceptable.

[Assessment of regional wall motion using strain Doppler imaging during right ventricular bifocal pacing in a patient with severe congestive heart failure: a case report].

A 79-year-old man presented with dilated cardiomyopathy and chronic atrial fibrillation. A DDD pacemaker was implanted due to sick sinus syndrome. His left ventricular ejection fraction was 23%. He was repeatedly admitted with congestive heart failure. Although cardiac resynchronization therapy was attempted, insertion of a pacing lead into the coronary sinus failed. Right ventricular bifocal pacing was done. The QRS width was shortened to 155 msec during bifocal pacing and 157 msec during right ventricular outflow pacing from 221 msec during right ventricular apical pacing. Heart failure was improved from New York Heart Association class III to II. Regional wall motion was assessed by strain of the myocardium. Bifocal pacing increased stroke volume due to improvement of longitudinal dyssynchrony of the septal and lateral walls. Bifocal pacing is effective for patients with severe congestive heart failure in whom biventricular pacing therapy has failed. Strain Doppler imaging is useful for the assessment of regional wall motion during cardiac pacing.

Assessment of the chronotropic response at the anaerobic threshold: an objective measure of chronotropic function.

The evaluation of the heart rate response to exercise is important for the diagnosis of chronotropic incompetence and the assessment of a rate responsive algorithm of sensor-controlled pacemakers. The aim of the present study was to examine a classification of the chronotropic response at an individually moderate exercise level. Sixteen pacemaker patients (patient group, age 62.9 +/- 7.6 years) with sick sinus syndrome and 15 age-matched healthy subjects (control group, age 57.6 +/- 9.4 years) underwent a maximum cardiopulmonary exercise test on a treadmill after a protocol with individually selected incremental steps. To analyze the patients' intrinsic heart rate response, the rate responsive mode of the pacemaker was switched off. Chronotropic incompetence was diagnosed in eight patients whose maximal heart rate was < 80% of the age-predicted heart rate. The heart rate at the anaerobic threshold was significantly lower in the chronotropically incompetent subgroup than in the chronotropically competent patients and the healthy subjects (85.9 +/- 6.6 beats/min vs 100.3 +/- 9.9 beats/min and 112.9 +/- 11.7 beats/min, respectively). The chronotropic slope of the heart rate reserve as a function of the metabolic reserve was significantly higher in the control group than in the patient groups with either mild or severe chronotropic incompetence (0.94 +/- 0.17 vs 0.64 +/- 0.08 and 0.43 +/- 0.14, respectively). Furthermore, the chronotropically incompetent response could be divided into a linear type with and without a threshold, an exponential, and a logarithmic type. The anaerobic threshold was an objectively detectable breakpoint at an individually moderate exercise level that could be used for characterization of chronotropic function. At the anaerobic threshold, a physiological heart rate response was about 220--age--50 beats/min. A deviation of more than 10 beats/min below this physiological value characterized chronotropic incompetence.

The mode selection trial (MOST) in sinus node dysfunction: design, rationale, and baseline characteristics of the first 1000 patients.

BACKGROUND: More than 200,000 permanent pacemakers will be implanted in the United States in 2000 at a cost of more than $2 billion. Sick sinus syndrome (SSS) will likely account for approximately half of all cases necessitating implantation. Pacemaker technology permits the selection of ventricular (single-chamber) or dual-chamber devices. However, clinical and outcomes data are inadequate to support a clear recommendation that one or the other type of device be used. METHODS: The Mode Selection Trial (MOST) is a single-blind study supported by the National Heart, Lung, and Blood Institute designed to enroll 2000 patients with SSS. All patients will receive a DDDR pacemaker programmed to VVIR or DDDR before implantation. The average time of follow-up will be 3 years. MOST has a >90% power to detect a 25% reduction in the primary end point-nonfatal stroke or total (all cause) mortality-in the DDDR-treated group. Secondary end points will include health-related quality of life and cost effectiveness, atrial fibrillation, and development of pacemaker syndrome. Prespecified subgroups for analysis will include women and the elderly. Enrollment was completed in October 1999, with a total of 2010 patients. RESULTS: The median age of the first 1000 enrolled patients is 74 years, with 25% of patients 80 years or older. Women comprise 49%, and 17% are nonwhite, predominantly black (13%). Before pacemaker implantation, 22% of patients reported a history of congestive heart failure, 11% coronary angioplasty, and 25% coronary bypass surgery. Supraventricular tachycardia including atrial fibrillation was present in 53% of patients. A prior stroke was reported by 12%. Antiarrhythmic therapy was in use in 18% of patients. CONCLUSIONS: MOST will fill the clinical need for carefully designed prospective studies to define the benefits of dual-chamber versus single-chamber ventricular pacing in patients with SSS. The MOST population is typical of the overall pacemaker population in the United States. Thus the final results of MOST should be clinically generalizable.

Sinus node recovery time assessment by the overdrive suppression test employing an intravenous injection of disopyramide phosphate.

Although sinus node recovery time (SNRT) assessment by the overdrive suppression test (ODST) is important in detecting sick sinus syndrome (SSS), its sensitivity is still inadequate. We have evaluated the effect of intravenous injection (i.v.) of disopyramide phosphate (DP) in ODST. The subjects were 30 SSS patients (64.9 +/- 10.0 years old). If SNRT was <2,000 ms or the corrected SNRT (CSNRT) was < 1,000 ms, ODST was repeated after DP i.v. (2 mg. kg(-1), < or = 100 mg in total). Eleven normal subjects (59.3 +/- 9.0 years old) were also studied. Although SNRT was <2,000 ms or the CSNRT was < 1,000 ms in 13 of the 30 SSS patients (43%), SNRT was prolonged from 1,510 +/- 300ms to 3,400 +/- 1,160 ms (P<0.01), and CSNRT from 510 +/- 190 to 2,470 +/- 1,470 ms (P<0.01) after DP i.v. in these patients. Thus, SNRT was > or = 2,000 ms and the CSNRT was > or = 1,000 ms in 27 of 30 SSS patients (90%) after DP i.v. Using a combination of overdrive suppression and intravenous injection of disopyramide phosphate, the corrected sinus node recovery time was diagnostic (>525 ms) in 29 of the 30 patients (97%). In contrast, SNRT and CSNRT were shortened in the normal subjects during ODST after DP i.v. (P<0.01). The plasma concentration of DP estimated in nine patients was 4.1 +/- 1.0 microg.ml(-1). No serious side effect occurred. ODST employing DP i.v. is safe and seems to be highly effective in diagnosing SSS.