TABLE 1.
Characteristics of included studies according to the effective of BBs on CEs.
| Study (Ref. no) | Study design | No. of participant (female,%) | The percentage of treated with BBs, % | Prescribed BBs and dose | Follow-up duration, yrs | Mean QTc value | Definition of CEs | Mean ages, yrs | Included LQTS genotype(s) |
|---|---|---|---|---|---|---|---|---|---|
| Moss et al. (2000) | ITS | 869 (62.3) | 100 | Atenolol: 1.36 ± 0.8 (mg/kg/day) | 5 | Probands: 520 ± 60 | Syncope, ACA,SCD | 15.7 | LQT1, LQT2, LQT3 |
| Metoprolol: 1.8 ± 1.1 (mg/kg/day) | |||||||||
| Nadolol: 1.4 ± 1.0 (mg/kg/day) | Affected family members: 500 ± 40 | ||||||||
| Propranolol: 2.9 ± 1.8 (mg/kg/day) | |||||||||
| Conrath et al. (2002) | ITS | 87 (females: 55.2, girls: 13.8, males: 16.0, boys: 15.0) | 100 | NS | 5.5 ± 5.7 | Boys, LQT1: 504 ± 10 | NS | NS | LQT1, LQT2 |
| LQT2: 488 ± 9 | |||||||||
| Girls, LQT1: 485 ± 9 | |||||||||
| LQT2: 461 ± 19 | |||||||||
| Males, LQT1: 472 ± 10 | |||||||||
| LQT2: 494 ± 12 | |||||||||
| Females, LQT1: 502 ± 19 | |||||||||
| LQT2: 493 ± 8 | |||||||||
| Chatrath et al. (2004) | Cohort | 28 (71.4) | 100 | Atenolol, metoprolol, Nadolol: 0.75–1.25 mg/kg/day | 4 | 507 ± 67 | Syncope, ACA | 19.8 ± 11.9 | LQT1, LQT2, LQT3 |
| Propranolol: 2.5–4 mg/kg/day | |||||||||
| Priori et al. (2004) | ITS | 335 (62) | 100 | Nadolol: 1.2 ± 0.5 mg/kg/day | 4.7 (0.6–36) | 492 ± 47 | ACA, SCD | 26 ± 17 | LQT1, LQT2, LQT3 |
| Propranolol: 2.2 ± 1.04 mg/kg/day | |||||||||
| Wang and Wu (2004) | ITS | 26 (65.3) | 84.6 | Metoprolol: 67.5 ± 39.1 mg/day | 3.1 ± 1 | 560 ± 60 | Syncope | 19 ± 10 | LQT1, LQT2 |
| Propranolol: 60.0 ± 5.5 mg/day | |||||||||
| Goldenberg et al. (2008) | Cohort | 3,015 children (girls: 63) | 21.3 | Atenolol, female: 75 ± 51 mg/day | Female: 11.6 ± 1.7 | Female: 493 ± 49 | Syncope, ACA, SCD | 7.5 ± 5.4 | LQT1, LQT2, LQT3 |
| Male: 85 ± 61 mg/day | |||||||||
| Metoprolol, female: 119 ± 72 mg/day | |||||||||
| Male: 89 ± 55 mg/day | |||||||||
| Nadolol, female: 57 ± 49 mg/day | Male: 489 ± 48 | Male: 489 ± 48 | |||||||
| Male: 50 ± 35 mg/day | |||||||||
| Propranolol, female: 51 ± 35 mg/day | |||||||||
| Male: 51 ± 34 mg/day | |||||||||
| Vincent et al. (2009) | ITS | 216 (64) | 100 | Nadolol, 2.2 ± 1.1 mg/kg/day | 12.5 (7–26) | 495 ± 46 | Syncope, ACA, SCD | 26 (18–42) | LQT1 |
| Propranolol, 1.7 ± 0.79 mg/kg/day | |||||||||
| Shimizu et al. (2009) | Cohort | 858 (27.8) | 23.4 | NS | 41 | Rochester: 490 ± 60 | Syncope, ACA, SCD | Rochester: 25 ± 20 | LQT2 |
| Netherlands: 470 ± 50 | Netherlands: 33 ± 21 | ||||||||
| Japan: 490 ± 50 | Japan: 30 ± 18 | ||||||||
| Mayo: 470 ± 50 | Mayo: 22 ± 16 | ||||||||
| Goldenberg et al. (2010) | Cohort | 971 (58.7) | 57.2 | Atenolol: 49 ± 32 mg/day | LQT1: 5.0 ± 6.8 | QTc ≥ 500 (34.5%) | Syncope, ACA, SCD | 31 ± 12 | LQT1, LQT2 |
| Metoprolol: 67 ± 55 mg/day | |||||||||
| Nadolol: 58 ± 45 mg/day | LQT2: 6.1 ± 7 | ||||||||
| Propranolol: 96 ± 71 mg/day | |||||||||
| Goldenberg et al. (2012) | Cohort | 721 (45.3) | 43.8 | NS | NS | CE triggered by four factor or no event | Syncope, ACA, SCD | 30 ± 12 | LQT1 |
| Exercise: 504 ± 52 | |||||||||
| Acute arousal: 491 ± 49 | |||||||||
| Sleep/rest nonarousal: 486 ± 58 | |||||||||
| Other triggers: 480 ± 48 | |||||||||
| No event: 471 ± 43 | |||||||||
| Chockalingam et al. (2012) | Cohort | 382 (56) | 100 | Metoprolol: 1.4 (0.9–2.5) | Propranolol: 2 (1–6) | 472 ± 46 | Syncope, ACA, SCD | 14 (8–32) | LQT1, LQT2 |
| Nadolol: 0.8 | Metoprolol: 4 (2–8) | ||||||||
| Propranolol: 2.5 (1.3–3) | Nadolol: 3 (2–5) | ||||||||
| Abu-zaitone et al. (2014) | Cohort | 1,530 (60.1) | 45.1 | Atenolol, Age>18 years: 0.7 ± 0.3 | 5 | Atenolol: 492 ± 49 | Syncope, ACA, SCD | 14.9 | LQT1, LQT2 |
| Age<18 years: 1.0 ± 0.7 | |||||||||
| Metoprolol, Age>18 years: 1.2 ± 0.9 | Metoprolol: 496 ± 52 | ||||||||
| Age<18 years: 1.4 ± 1.0 | |||||||||
| Nadolol, Age>18 years: 1.0 ± 0.8 | Nadolol: 490 ± 51 | ||||||||
| Age<18 years: 1.0 ± 0.8 | |||||||||
| Propranolol, Age>18 years: 2.1 ± 2.3 | Propranolol: 500 ± 58 | ||||||||
| Age<18 years: 2.3 ± 1.5 | |||||||||
| Koponen et al. (2015) | Cohort | 316 (53.1) | 77.2 | Metoprolol: 1.3 ± 0.4 (mg/kg/day) | 5.8 | LQT1 mutation (G589D): 454 ± 35 | Syncope, ACA, SCD | 12.0 ± 5.5 | LQT1, LQT2 |
| Mutation (c.1129–2A > G): 465 ± 37 | |||||||||
| Bisoprolol: 0.1 ± 0.1 (mg/kg/day) | Non-mutation: 475 ± 43 LQT2 | ||||||||
| Atenolol: 1.2 ± 1.5 (mg/kg/day) | Mutation (L552S): 448 ± 32 | ||||||||
| Propranolol: 2.4 ± 0.8 (mg/kg/day) | Mutation (R176W): 436 ± 31 | ||||||||
| Non-mutation: 480 ± 39 | |||||||||
| Steinberg et al. (2016) | Cohort | 114 (58.7) | 100 | Atenolol: 53 ± 30 mg/day | Atenolol: 6 (3–10) | Atenolol: 466 ± 23 | Syncope, ACA, VT | Atenolol: 37 ± 19 | LQT1, LQT2 |
| Nadolol: 74 ± 47 mg/day | Nadolol: 3 (1–5) | Nadolol: 469 ± 32 | Nadolol: 27 ± 13 | ||||||
| Wilde et al. (2016) | Cohort | 391 (55) | 29 | ND | 7.25 | 476 ± 57 | Syncope, ACA, SCD | 28 ± 20 | LQT3 |
| Mazzanti et al. (2018) | Cohort | 1710 (52) | ND | Nadolol: >0.5 mg/kg/day | 9 ± 7 | 471 ± 45 | Syncope,ACA, SCD | ND | LQT1, LQT2, LQT3 |
| Propranolol: >1.5 mg/kg/day | |||||||||
| Metoprolol: >1.0 mg/kd/day |
BBs: beta-blockers; LQTS: long-QT syndromes; ITS: interrupted time series; ACA: aborted cardiac death; SCD:sudden cardiac death; VT: ventricular tachycardia.