TABLE 1.
Subject characteristics, inclusion, and exclusion criteria.
| Citation | Sample size | Age (years) | Sex | Health status, LQTS type & QTc (ms) | Inclusion & exclusion criteria |
|---|---|---|---|---|---|
| Hermans et al. (2020) |
Study cohort (Amsterdam): n = 678 Control = 345 cLQTS = 333 External cohort (Leuven): n = 117 Control = 45 cLQTS = 72 |
Amsterdam: 45 ± 15 (control) 42 ± 15 (LQT1) 42 ± 15 (LQT2) 40 ± 15 (LQT3) Leuven: 42.8 ± 16.6 (control) 44.3 ± 9.4 (LQT1) 35.7 ± 15 (LQT2) 34.8 ± 10.2 (LQT3) |
Amsterdam: F: 185 (control) 77 (LQT1) 87 (LQT2) 32 (LQT3) M: 160 (control) 49 (LQT1) 69 (LQT2) 19 (LQT3) Leuven: F: 27 (control) 12 (LQT1) 23 (LQT2) 5 (LQT3) M: 18 (control) 4 (LQT1) 28 (LQT2) 0 (LQT3) |
Amsterdam: Control (410 ± 28) LQT1 (455 ± 34) LQT2 (462 ± 36) LQT3 (446 ± 50) Leuven: Control (402 ± 27) LQT1 (467 ± 44) LQT2 (455 ± 34) LQT3 (421 ± 11) |
Age ≥ 16 years Known genetic testing results Digitally available ECG at first presentation Exclusion: age < 16 years, absence genetic testing results, absence baseline data, pathologies and medications that affect TWM |
| Hermans et al. (2018) |
n = 688 Control = 348 LQT1 = 129 LQT2 = 160 LQT3 = 51 |
45 ± 15 (control) 42 ± 15 (LQT1) 42 ± 15 (LQT2) 40 ± 15 (LQT3) |
F: 185 (control) 77 (LQT1) 88 (LQT2) 32 (LQT3) M: 163 (control) 52 (LQT1) 72 (LQT2) 19 (LQT3) |
Control LQT1 LQT2 LQT3 QTc‐interval cut‐off: >480 |
Age ≥ 16 years Known genetic testing results Digitally available ECG at first presentation Exclusion: comorbidity affecting ventricular re‐ and/or depolarization (BBB hypokalemia, thalassemia, angina pectoris, BrS overlap, severe post‐anoxic encephalopathy), ECG parameters (excessive noise, TW flattening <40 μV, export failure) |
| Platonov et al. (2018) |
n = 1161 Control = 1007 LQT2 = 154 |
41 ± 15 |
F: 593 (control) 87 (LQT2) M: 414 (control) 67 (LQT2) |
Control (417 ± 26) LQT2 with normal QTc (436 ± 23) |
Rochester‐LQTS registry KCNH2 mutation (LQT2) QTc <470 ms (F), <460 ms (M) ≤18 years Exclusion: ≥1 mutation |
| Porta‐Sanchez et al. (2017) |
n = 108 Control = 45 LQT1 = 43 LQT2 = 20 |
35.4 ± 17.3 (control) 41.7 ± 17.4 (LQTS) |
F: 66.7% (control) 67.4% (LQT1) 60% (LQT2) M: 33.3% (control) 32.6% (LQT1) 40% (LQT2) |
Control (418 ± 24) LQT1 (486 ± 50) LQT2 (479 ± 36) |
No QT prolonging drugs No reversible causes QTc prolongation LQTS: gene positive Control: normal ECG, echocardiogram, cardiology review |
| Sugrue, Noseworthy, et al. (2017) |
n = 152 LQT1 = 15 LQT2 = 23 aLQTS = 114 |
15 ± 12 (cLQTS) 66 ± 14 (aLQTS) |
F: 30 (75%, cLQTS) 69 (53%, aLQTS) M: 8 (25%, cLQTS) 45 (47%, aLQTS) |
cLQTS (500 ± 30) aLQTS (520 ± 29) |
Mayo Clinic's QT‐alert system cLQTS CredibleMeds QT drug list (≤7 days) Hypokalemia <3.6 mm/L Hypomagnesemia <1.7 mg/dL Hypocalcemia <4.65 mg/dL (ionized) Exclusion: BBB, ventricular pacing, AF, atrial flutter, SVT, ST‐T ischemic changes, LVH, uninterpretable ECG, tracing interference, biphasic TW |
| Sugrue, Rohatgl, et al. (2017) |
n = 491 LQT1 = 246 LQT2 = 161 |
16 (median age at first Mayo clinic ECG) |
F: 235 (85%) M: 172 (42%) |
LQT1 (456.5) LQT2 (455) |
Mayo Clinic LQT cohort (1999–2015) Genotype positive LQT1, LQT2 Exclusion: LQT3, LQT4, multiple LQTS‐associated mutations, BBB, ventricular pacing, AF, uninterpretable ECG, biphasic TW, missing ECG lead data |
| Immanuel et al. (2016) |
n = 419 Control = 159 LQT1 = 171 LQT2 = 89 |
35.6 ± 14.6 (control) 28.2 ± 17.7 (LQT1) 28.6 ± 18.7 (LQT2) |
F: 75 (control) 78 (LQT1) 29 (LQT2) M: 65 (control) 55 (LQT1) 32 (LQT2) |
Control LQT1 LQT2 Subgroup with normal QTc (400–450) |
THEW database Children and adults Genotype positive LQT1, LQT2 Upright TWs Exclusion: abnormal TWs (flat, biphasic) |
| Sugrue et al. (2016) |
n = 840 Control = 420 LQT1 = 257 LQT2 = 163 |
22 ± 16 (control) 23 ± 16 (LQT1) 22 ± 15 (LQT2) |
F: (57%) M: (43%) |
Control (424 ± 18) LQT1 (462 ± 37) LQT2 (464 ± 46) |
Control: no cardiac disease Genotype positive LQT1, LQT2 Concealed LQTS: QTc <460 ms (F), <450 ms (M), <440 ms (children, both sexes) Exclusion: uninterpretable ECG, tracing interference, biphasic or low amplitude TW |
| Sugrue et al. (2015) |
n = 39 Control = 26 TdP = 13 Sotalol = 8 Dofetilide = 5 |
60.3 ± 14.5 (sotalol) Control = 61.4 ± 14 68.4 ± 5.5 (dofetilide) Control = 68 ± 5.4 |
F: 20 (51%, control) Sotalol control = 12 Dofetilide control = 8 6 (15%, sotalol) 4 (10%, dofetilide) M: 6 (15%, control) Sotalol control = 4 Dofetilide control = 2 2 (5%, sotalol) 1 (2.6%, dofetilide) |
Control TdP post drug initiation |
Electronic medical record search Admitted for initiation of sotalol or dofetilide (AF, atrial flutter, VE, VT) Serial ECGs Documentation of TdP No previous TdP Exclusion: paced rhythm, drug ceased due to QT prolongation, chronic use of drug |
| Vicente et al. (2015) | n = 22 | 26.9 ± 5.5 |
F: 11 (50%) M: 11 (50%) |
Healthy (395.9 ± 17.1) |
Healthy: physician assessment, no history of heart disease or unexplained syncope or a family history of LQTS QTc (Fridericia) <450 ms (M), <470 ms (F) 18–35 years of age Weight ≥ 50 kg BMI 18–27 kg/ m2 Able to read and understand the informed consent Exclusion: >10 ectopic beats (3 hr continuous ECG recording at screening) |
| Johannessen et al. (2014) | n = 22 | 26.9 ± 5.5 |
F: 11 (50%) M: 11 (50%) |
Healthy (395.9 ± 17.1) |
Healthy: physician assessment, no history of heart disease or unexplained syncope or a family history of LQTS QTc <450 ms (M), <470 ms (F) 18–35 years of age Weight ≥ 50 kg BMI 18–27 kg/ m2 Able to read and understand the informed consent Exclusion: >10 ectopic beats at screening (3 hr continuous ECG) |
| Couderc et al. (2011) |
n = 704 Control = 411 LQT2 Noncarrier = 150 Carrier = 143 |
40 ± 14 (control) 39 ± 14 (LQT2 noncarrier) 38 ± 15 (LQT2 carrier) |
F: 267 (65%, control) 86 (57%, LQT2 noncarrier) 87 (61%, LQT2 carrier) M: 144 (35%, control) 64 (43%, LQT2 noncarrier) 56 (39%, LQT2 carrier) |
Control (411 ± 23) Healthy on moxifloxacin (422 ± 26) LQT2 Noncarrier (405 ± 29) Carrier (470 ± 47) |
Age > 17 years LQT2 families Adequate quality ECG trace |
| Graff et al. (2010) |
n = 145 Placebo = 62 Moxifloxacin = 62 Sotalol = 21 |
18 to 45 |
F: 26 (placebo) 24 (moxifloxacin) 0 (sotalol) M: 36 (placebo) 38 (moxifloxacin) 21 (sotalol) |
Healthy |
Healthy: history, exam, normal ECG, normal laboratory tests, no medications, negative pregnancy test, reliable contraception Exclusion: LQTS, TdP risk factors, concomitant medication use, fluoroquinolone hypersensitivity, unable to have moxifloxacin based on screening |
| Graff et al. (2009) |
n = 986 Control = 917 LQT2 = 30 Sotalol = 39 |
29 ± 7 (control) 45 ± 14 (LQT2) |
F: 146 (15%, control) 19 (2%, LQT2) 11 (1%, sotalol) M: 771 (78%, control) 11 (1%, LQT2) 28 (2.8%, sotalol) |
Control (407 ± 18) LQT2 (483 ± 35) Sotalol (403 ± 15 to 459 ± 14) |
Healthy: history, exam, no medications LQT2: confirmed hERG mutation Exclusion: poor Holter ECG tracings |
| Vaglio et al. (2008) |
n = 112 Control = 38 LQT1 = 49 LQT2 = 25 |
27.5 ± 8.1 (control) 34.3 ± 10.2 (LQT1) 35.5 ± 9.4 (LQT2) |
F: 11 (29%, control) 34 (71%, LQT1) 19 (76%, LQT2) M: 27 (71%, control) 15 (29%, LQT1) 6 (24%, LQT2) |
Control (413 ± 17) LQT1 (493 ± 29) LQT2 (510 ± 41) |
Healthy: nonmutation carriers, normal QTc KCNH2 and KvLQT1 gene positive (26 LQT1 and 19 LQT2 families) |
| Kanters et al. (2004) |
n = 50 Control = 13 hERG = 24 KvLQT1 = 13 |
>14 |
F: 9 (control) 16 (hERG) 8 (KvLQT1) M: 4 (control) 8 (hERG) 5 (KvLQT1) |
Control (healthy) (378 ± 11) hERG (498 ± 13) KvLQT1 (479 ± 13) |
Danish LQTS Clinic hERG or KvLQT1 genotype positive Control: healthy, unaffected (genotype negative from same families) Age > 14 years Artifact‐free ECG |
| Moss et al. (1995) |
n = 153 Six LQTS families U = 77 A = 76 Chromosome 3 (n = 47) U = 28 A = 19 Chromosome 7 (n = 30) U = 13 A = 17 Chromosome 11 (n = 76) U = 36 A = 40 |
Chromosome 3: Family 1: 20 ± 17 (U) 27 ± 20 (A) Family 2: 30 ± 19 (U) 19 ± 13 (A) Chromosome 7: Family 3: 35 ± 23 (U) 27 ± 17(A) Family 4: 29 ± 13 (U) 29 ± 24 (A) Chromosome 11: Family 5: 19 ± 19 (U) 15 ± 12 (A) Family 6: 24 ± 23 (U) 27 ± 25 (A) |
Chromosome 3: (F/M) Family 1: 9/13 (U) 3/10 (A) Family 2: 4/2 (U) 2/4 (A) Chromosome 7: (F/M) Family 3: 1/2 (U) 4/1 (A) Family 4: 6/4 (U) 6/6 (A) Chromosome 11: (F/M) Family 5: 2/5 (U) 4/3 (A) Family 6: 17/12 (U) 23/10 (A) |
Chromosome 3: Family 1: 417 ± 35 (U) 535 ± 46(A) Family 2: 420 ± 30 (U) 523 ± 40 (A) Chromosome 7: Family 3: 407 ± 12 (U) 502 ± 49 (A) Family 4: 410 ± 35 (U) 458 ± 51 (A) Chromosome 11: Family 5: 417 ± 49 (U) 514 ± 44 (A) Family 6: 416 ± 36 (U) 491 ± 43 (A) |
LQTS family Genotype positive Control: healthy, genotype negative from same families Exclusion: congenital hearing loss, left cervicothoracic sympathetic ganglionectomy |
Abbreviations: A, affected; AF, atrial fibrillation; aLQTS, acquired long QT syndrome; BBB, bundle branch block; BMI, body mass index; BrS, Brugada syndrome; cLQTS, congenital long QT syndrome; ECG, electrocardiogram; F, female; LQT1, long QT syndrome type 1; LQT2, long QT syndrome type 2; LQTS, long QT syndrome; LVH, left ventricular hypertrophy; M, male; QTc, corrected QT interval; ST‐T, ST‐T segment; SVT, supraventricular tachycardia; TdP, torsades de pointes; TW, T wave; TWM, T wave morphology; U, unaffected; VE, ventricular ectopy; VT, ventricular tachycardia.