Mode Selection Trial in Sinus Node Dysfunction (MOST)

2014-08-27 04:00:04 | BioPortfolio


To determine if dual chamber rate-modulated pacing (DDDR) in patients with sick sinus syndrome is superior to single chamber pacing (VVIR) with respect to subsequent frequency of adverse clinical events such as stroke, quality of life and function, and cost effectiveness.



Permanent pacing is estimated to cost one billion dollars annually in health care costs in the United States. Initially, pacing was primarily confined to ventricular pacing with limited sensing, programming and pacing capacity. Tremendous growth has occurred in pacing technology, making available dual chamber pacing with sophisticated sensing, pacing, and rate control. These more advanced pacemakers are more costly and complicated to place surgically.

One of the most common indications for pacing is sick sinus syndrome. Initial therapy is usually medical to inhibit the tachyarrhythmias (most commonly paroxysmal atrial fibrillation). However, if symptomatic bradycardia results, then permanent pacing is commonly employed. The appropriate type of pacing in this setting is not clearly defined and is controversial.

The development of atrioventricular pacing was principally aimed at improving cardiac hemodynamics and creating a more physiological heart rate control. Hemodynamic studies have clearly shown the benefit of this approach in many patients, particularly those with decreased left ventricular compliance in whom atrial activity contributes significantly to cardiac output. Lack of synchronization between the upper and lower chambers of the heart caused by pacing the ventricle alone can result in a constellation of symptoms commonly referred to as "pacemaker syndrome".

The underlying mechanisms by which dual chamber pacing is purported to improve outcome is straightforward; in patients with normal sinus rhythm, cardiac output is improved by 15 to 30 percent. In addition, a number of retrospective studies that have compared single chamber with atrial-based or dual chamber pacing have suggested that the latter may prevent adverse clinical events such as atrial fibrillation, congestive heart failure, cerebral vascular accidents, and death. While none of these studies was a randomized trial, the literature is consistent with a concept that dual mode pacing results in improved hemodynamics and a more favorable outcome in patients with sick sinus syndrome. However, the data do not provide definitive answers because of small sample sizes and methodological problems. A major problems with all previous studies is probable selection bias favoring implantation of dual chamber devices in younger, healthier patients.

Several small studies have compared functional status and other quality of life measures between single and dual chamber pacing modes and have suggested better quality of life outcomes for the dual chamber mode. Again, these conclusions are severly hampered by the sample sizes, the lack of random assignment or adequate statistical adjustment to control for confounding, use of outdated and/or invalid measures, and potential response bias due to awareness of mode assignment.


A multicenter, randomized clinical trial. All patients received a dual chamber pacemaker capable of either single or dual chamber rate modulated pacing. Patients were then randomized to either the single chamber mode or the dual chamber mode. Patients with prior stroke were pre-stratified. Clinical and electrocardiographic data were collected during a 1.5 to 4.5 year follow-up. The primary endpoint was either: first occurrence of stroke, or; total (all-cause) mortality. Secondary endpoints included health status, cost-effectiveness, cardiovascular mortality, composite of any of the three major adverse effects expected in sick sinus syndrome patients (total mortality alone or first stroke or congestive heart failure hospitalization), first occurrence of atrial fibrillation, heart failure score, pacemaker syndrome, health status in women and in the elderly, and outcome of patients with risk factors for pacemaker syndrome. Enrollment was completed in October, 1999 with a total of 2,010 patients.

Quality of life and economic issues were assessed in patients at entry and annually for three years. Questionnaire-based measures of health status and quality of life were compared in the two pacing groups for the entire population and subgroups defined by age and gender. The economic substudy measured the comparative costs, both direct and indirect medical and nonmedical, of the two pacing modes in an attempt to determine the most cost-effective approach to pacemaker treatment of sick sinus syndrome.

Recruitment started October 1, 1995 and was completed October 4, 1999 with 2,010 patients enrolled.

Study Design

Allocation: Randomized, Primary Purpose: Treatment




pacemaker, artificial




National Heart, Lung, and Blood Institute (NHLBI)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T04:00:04-0400

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A cardiac arrhythmia that is caused by interaction of two independently initiated cardiac impulses of different rates from two separate foci. Generally one focus is the SINOATRIAL NODE, the normal pacemaker. The ectopic focus is usually in the HEART VENTRICLE but can be in the HEART ATRIUM or the ATRIOVENTRICULAR NODE. Modulation of the parasystolic rhythm by the sinus rhythm depends on the completeness of entrance block surrounding the parasystolic focus.

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