古屋秀夫，田辺晃久：ホルター心電図法による上室不整脈の日内変動・日差変動に関する検討－薬効評価法の試みを含めて―．Jpn J Electrocardiology 1986;6:253-259．.
Cardiac Arrhythmia Suppression Trial (CAST) Investigators.
Preliminary report: effect of encainide and flecainide on mortality in a randomized trial of arrhythmia suppression after myocardial infarction.
N Engl J Med. 1989 Aug 10;321(6):406-12. doi: 10.1056/NEJM198908103210629.
Abstract/Text
The occurrence of ventricular premature depolarizations in survivors of myocardial infarction is a risk factor for subsequent sudden death, but whether antiarrhythmic therapy reduces the risk is not known. The Cardiac Arrhythmia Suppression Trial (CAST) is evaluating the effect of antiarrhythmic therapy (encainide, flecainide, or moricizine) in patients with asymptomatic or mildly symptomatic ventricular arrhythmia (six or more ventricular premature beats per hour) after myocardial infarction. As of March 30, 1989, 2309 patients had been recruited for the initial drug-titration phase of the study: 1727 (75 percent) had initial suppression of their arrhythmia (as assessed by Holter recording) through the use of one of the three study drugs and had been randomly assigned to receive active drug or placebo. During an average of 10 months of follow-up, the patients treated with active drug had a higher rate of death from arrhythmia than the patients assigned to placebo. Encainide and flecainide accounted for the excess of deaths from arrhythmia and nonfatal cardiac arrests (33 of 730 patients taking encainide or flecainide [4.5 percent]; 9 of 725 taking placebo [1.2 percent]; relative risk, 3.6; 95 percent confidence interval, 1.7 to 8.5). They also accounted for the higher total mortality (56 of 730 [7.7 percent] and 22 of 725 [3.0 percent], respectively; relative risk, 2.5; 95 percent confidence interval, 1.6 to 4.5). Because of these results, the part of the trial involving encainide and flecainide has been discontinued. We conclude that neither encainide nor flecainide should be used in the treatment of patients with asymptomatic or minimally symptomatic ventricular arrhythmia after myocardial infarction, even though these drugs may be effective initially in suppressing ventricular arrhythmia. Whether these results apply to other patients who might be candidates for antiarrhythmic therapy is unknown.
Binici Z, Intzilakis T, Nielsen OW, Køber L, Sajadieh A.
Excessive supraventricular ectopic activity and increased risk of atrial fibrillation and stroke.
Circulation. 2010 May 4;121(17):1904-11. doi: 10.1161/CIRCULATIONAHA.109.874982. Epub 2010 Apr 19.
Abstract/Text
BACKGROUND: Prediction of stroke and atrial fibrillation in healthy individuals is challenging. We examined whether excessive supraventricular ectopic activity (ESVEA) correlates with risk of stroke, death, and atrial fibrillation in subjects without previous stroke or heart disease.
METHODS AND RESULTS: The population-based cohort of the Copenhagen Holter Study, consisting of 678 healthy men and women aged between 55 and 75 years with no history of cardiovascular disease, atrial fibrillation, or stroke, was evaluated. All had fasting laboratory tests and 48-hour ambulatory ECG monitoring. ESVEA was defined as >or=30 supraventricular ectopic complexes (SVEC) per hour or as any episodes with runs of >or=20 SVEC. The primary end point was stroke or death, and the secondary end points were total mortality, stroke, and admissions for atrial fibrillation. Median follow-up was 6.3 years. Seventy subjects had SVEC>or=30/h, and 42 had runs of SVEC with a length of >or=20 SVEC. Together, 99 subjects (14.6%) had ESVEA. The risk of primary end point (death or stroke) was significantly higher in subjects with ESVEA compared with those without ESVEA after adjustment for conventional risk factors (hazard ratio=1.64; 95% confidence interval, 1.03 to 2.60; P=0.036). ESVEA was also associated with admissions for atrial fibrillation (hazard ratio=2.78; 95% confidence interval, 1.08 to 6.99; P=0.033) and stroke (hazard ratio=2.79; 95% confidence interval, 1.23 to 6.30; P=0.014). SVEC, as a continuous variable, was also associated with both the primary end point of stroke or death and admissions for atrial fibrillation.
CONCLUSIONS: ESVEA in apparently healthy subjects is associated with development of atrial fibrillation and is associated with a poor prognosis in term of death or stroke.
Tasaki H, Serita T, Ueyama C, Kitano K, Seto S, Yano K, Camm AJ.
Longitudinal age-related changes in 24-hour total heart beats and premature beats and their relationship in healthy elderly subjects.
Int Heart J. 2006 Jul;47(4):549-63. doi: 10.1536/ihj.47.549.
Abstract/Text
The aim of this study was to conduct a longitudinal follow-up on age-related changes in 24-hour total heart beats (THBs) and total premature beats and their correlations in healthy elderly subjects. In 15 healthy elderly subjects (mean age, 70.0 +/- 4.1, age range at 1st recording, 64 to 80 years, 10 females, 5 males), we conducted Holter monitoring twice at an interval of 15 years and analysed age-related changes in THBs, atrial premature beats (APBs), and ventricular premature beats (VPBs), as well as their correlations. The results indicated that THBs, APBs, and VPBs all significantly increased with age in the healthy elderly subjects at a mean age of 70.0 +/- 4.1 (THB: 91074.1 +/- 11515.3 versus 99457.5 +/- 12131.0; P = 0.0004, APB:119.2 +/- 97.8 versus 884.4 +/- 1193.8; P = 0.0008, VPB: 15.2 +/- 53.6 versus 140.7 +/- 228.9; P = 0.0328). Moreover, we divided the subjects into increase and nonincrease groups based on the age-related changes in APB and VPB for 15 years ([n]; Inc-APB: Noninc-APB = 6 : 9, Inc-VPB: Noninc-VPB = 5 : 10). In the increase groups, premature beats tended to increase in proportion to changes in THBs with age (APB: Y = 207.488 + 0.136 X, r = 0.848, P = 0.0303; VPB: Y = -27.594 + 0.028 X, r = 0.727, P = 0.1921). In conclusion, this 15-year follow-up of Holter recordings in healthy elderly subjects revealed that THBs, APBs, and VPBs increased with age, and that the increases in premature beats, especially APBs, were in proportion to those in THBs.
