The Mode Selection Trial (MOST) in sinus node dysfunction: Design, rationale, and baseline characteristics of the first 1000 patients

Lamas, Gervasio A.; Lee, Kerry; Sweeney, Michael O.; León, Angel R.; Yee, Raymond; Ellenbogen, Kenneth A.; Greer, Stephen; Wilber, David J.; Silverman, Russell; Marinchak, Roger A.; Bernstein, Robert C.; Mittleman, Robert S.; Lieberman, Eric H.; Sullivan, C. P.; Zorn, Lisa; Flaker, Greg; Schron, Eleanor B.; Orav, E. John; Goldman, Lee

doi:10.1067/mhj.2000.109652

Cited by 152 publications

(102 citation statements)

References 27 publications

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“…2,5 Follow-up for clinical outcomes occurred four times during the first year and twice per year thereafter and ended in January 2001. Enrollment and data collection have been outlined in detail.…”

Section: Methodsmentioning

confidence: 99%

“…2,4 Health-related QOL is an important metric of the efficacy of treatment, particularly in assessing treatments that do not clearly influence survival, and especially in older patients likely to suffer from sick sinus syndrome. Therefore, we collected and analyzed serial QOL in the Mode Selection Trial (MOST), a large trial of patients with sick sinus syndrome who were randomized to dual-chamber, rate-modulated (DDDR) or single-chamber, rate-modulated ventricular (VVIR) pacing 5 to assess the effect of pacemaker implantation, clinical factors, and mode on QOL. We hypothesized that dual-chamber pacing would be associated with greater improvement in QOL after pacemaker implantation.…”

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confidence: 99%

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Pacemaker implantation and quality of life in the Mode Selection Trial (MOST)

et al. 2006

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

Pacemaker implantation and quality of life in the Mode Selection Trial (MOST)

et al. 2006

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“…The dominant pacemaker of mammalian hearts is the sinoatrial node (SAN). Dysfunction or failure of SAN activity in humans may lead to an abnormally low heart rate, causing such symptoms as palpitations, fatigue, and syncope, which eventually require implantation of a pacemaker device (1). Elevated resting heart rate, in contrast, is associated with increased cardiovascular mortality and morbidity (2,3).…”

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Control of heart rate by cAMP sensitivity of HCN channels

Alig

Marger

Mesirca

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

105

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''Pacemaker'' f-channels mediating the hyperpolarization-activated nonselective cation current I f are directly regulated by cAMP. Accordingly, the activity of f-channels increases when cellular cAMP levels are elevated (e.g., during sympathetic stimulation) and decreases when they are reduced (e.g., during vagal stimulation). Although these biophysical properties seem to make f-channels ideal molecular targets for heart rate regulation by the autonomic nervous system, the exact contribution of the major I f-mediating cardiac isoforms HCN2 and HCN4 to sinoatrial node (SAN) function remains highly controversial. To directly investigate the role of cAMP-dependent regulation of hyperpolarization activated cyclic nucleotide activated (HCN) channels in SAN activity, we generated mice with heart-specific and inducible expression of a human HCN4 mutation (573X) that abolishes the cAMP-dependent regulation of HCN channels. We found that hHCN4 -573X expression causes elimination of the cAMP sensitivity of I f and decreases the maximum firing rates of SAN pacemaker cells. In conscious mice, hHCN4 -573X expression leads to a marked reduction in heart rate at rest and during exercise. Despite the complete loss of cAMP sensitivity of If, the relative extent of SAN cell frequency and heart rate regulation are preserved. Our data demonstrate that cAMPmediated regulation of If determines basal and maximal heart rates but does not play an indispensable role in heart rate adaptation during physical activity. Our data also reveal the pathophysiologic mechanism of hHCN4 -573X-linked SAN dysfunction in humans.bradycardia ͉ hyperpolarization cyclic nucleotide-gated ion channels ͉ pacemaker activity ͉ sinoatrial node ͉ transgenic mice H eart automaticity is a fundamental physiological function in higher organisms. The dominant pacemaker of mammalian hearts is the sinoatrial node (SAN). Dysfunction or failure of SAN activity in humans may lead to an abnormally low heart rate, causing such symptoms as palpitations, fatigue, and syncope, which eventually require implantation of a pacemaker device (1). Elevated resting heart rate, in contrast, is associated with increased cardiovascular mortality and morbidity (2, 3). Despite the importance of cardiac pacemaking as a physiological process, the complex mechanisms underlying SAN automaticity and heart rate regulation remain incompletely understood. SAN activity is controlled by the autonomic nervous system; cholinergic and ␤-adrenergic stimulation either slows or accelerates spontaneous SAN activity. Several ionic currents contribute to cardiac automaticity (4-6). Some of these currents are targets of regulation by the autonomic nervous system, but their physiological importance is a matter of debate (4, 5). ''Pacemaker'' f-channels mediating the hyperpolarizationactivated nonselective cation current I f , in particular, are directly regulated by cAMP (7). These channels are homotetrameric or heterotetrameric complexes of hyperpolarization-activated cyclic nucleotide-gated (HCN) subunits (8...

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“…2,8 Subjects were followed regularly for clinical outcomes 4 times during the first year and biannually thereafter until January 2001. Procedures for subject enrollment and data collection have been outlined in previous reports.…”

Section: Methodsmentioning

confidence: 99%

“…Therefore, we analyzed the serial QOL data from the MOST study, a large trial of 2,010 patients with sick sinus syndrome randomized to single-chamber ventricular (rate modulated right ventricular pacing [VVIR]) or dual-chamber (DDDR) pacing, 8 to assess the effect of AF on QOL. We hypothesized that QOL would be adversely affected in patients who developed AF during the trial and that cardiovascular functional status would also be adversely affected.…”

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confidence: 99%