www.QTFactors.org - Clinical Factors Associated with Prolonged QTc and/or TdP


CredibleMeds® maintains the following list of clinical factors that have been associated in the medical literature with prolonged QTc and/or Torsades de Pointes (TdP).  Factors are placed in this list based on a systematic review and analysis of all available evidence.  The quality of the evidence and the strength of associations are assessed using a modified GRADE scale (For definition, click here ).  We value your feedback and suggestions. 



Autonomic Nervous System
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Pheochromocytoma Yes High Yes High link
Alpha adrenergic stimulation Yes Moderate Yes Low link
Emotion (Arousal) Yes Moderate Yes Moderate link
Head-up tilt Yes High None No evidence link
Pure Autonomic Failure Yes High None No evidence link
Cold Water Immersion Yes Moderate Yes Moderate link
Parkinson's disease Yes Moderate None No evidence link


Cardiovascular Diseases
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Bradycardia, AV Block, Pause Yes High Yes High link
Takosubo (stress-related) Cardiomypathy Yes High Yes High link
Acute Myocardial Ischemia Yes Moderate Yes Low link
Stroke Yes High Yes Low link
Hypertension/LVH Yes Low Weak Very Low link
Mitral Valve Prolapse Yes Moderate Weak Very Low link
Cardiomyopathy/CHF Yes Moderate Weak Low link
Atrial Fibrillation Conversion Weak Moderate Yes Moderate link
Mitral valve stenosis Yes Moderate None No evidence link
Hypertrophic Cardiomyopathy Weak Low Weak Low link


Electrolyte Disorders
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Hypokalemia (≤3.5 mEq/L) Yes High Yes High link
Hypomagnesemia (≤ 1.7 mg/dL) Yes High Yes High link
Hypocalcemia (≤ 8.5 mg/dL) Yes High Yes High link
Hyperemesis (Anorexia Nervosa, Pregnancy) Yes Very Low Weak Very Low link
Diarrhea Yes Moderate Weak Very Low link
Licorice (Excessive ingestion) Yes High Yes Moderate link
Bartter Syndrome Yes Moderate Weak Very Low link
Hemodialysis Yes Moderate Weak Moderate link
Hypernatremia (extreme) Yes Low Yes Very Low link
Apheresis Yes High None No evidence link
Gitelman Syndrome Yes High None No evidence link
Hypoalbuminemia Weak Very Low None No evidence link


Endocrine Disorders
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Hypothyroidism Yes High Yes Moderate link
Hyperglycemia Yes Low Weak Very Low link
Diabetes Weak Very Low Weak Very Low link
Obesity (BMI ≥30) Weak Very Low None No evidence link
Leptin Yes Low None No evidence link
Decreased PI3 kinase (inc. INaL) Yes Low None No evidence link
Primary Aldosteronism Yes Moderate Yes Moderate link
Hypoglycemia Yes Low Yes Moderate link
Hyperthyroidism Yes Low Weak Very Low link
Panhypopituitarism Yes Moderate Yes High link
Hyperparathyroidism Yes High Weak Very Low link


Environmental Effects
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Hypothermia Yes High Yes Moderate link
Smoking Weak Low None No evidence link
Alcohol (excess) Weak Low None Very Low link
Herbal remedies Weak Low Weak Very Low link
Hypoxia, COPD, Sleep apnea Yes Moderate None Low link
Lead exposure Yes Low None No evidence link
Carbon Monoxide Yes Low None No evidence link
Chlorobutanol Yes Low Yes Low link
Omega 3 PUFA deficiency Weak Very Low None No evidence link


General Clinical
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Female Sex Yes High Yes High link
Age ≥ 65 yr Yes High Yes Low link
Renal failure (GFR ≤30 ml/min) Yes Low Yes Very Low link
Liver failure (cirrhosis) Yes Low None No evidence link
Pulmonary embolism Yes Moderate None No evidence link


Inflammation/Auto-immune
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Sepsis Yes Moderate Yes Moderate link
Systemic Lupus Erythematosus Yes Moderate None No evidence link
HIV Yes Low None No evidence link
C-Reactive protein Yes Low None No evidence link
Heat Shock Proteins Yes Low None No evidence link
Cytokines (TNFα, IL1β, IL6) Yes Moderate Weak Low link
Fever Yes Moderate Yes Low link
Inflammation/Rheum. Arthritis Yes Moderate Yes Moderate link
Sarcoidosis Yes Low Weak Very Low link
Anti SSA/Ro Antibody Yes Low Weak Very Low link
Multiple sclerosis Yes Low None No evidence link
Celiac disase Yes High None No evidence link
Psoriasis Weak Very Low None No evidence link
Cardiac Allograft Rejection Yes Low None No evidence link


Miscellaneous
Clinical Factor Clinical Association with Increased QT Quality of Evidence for Assoc. with Increased QT
(more info)
Clinical Association with TdP Quality of Evidence for Assoc. with TdP Pubmed Search Link
Pre-eclampsia Weak Low None No evidence link
Genotypic Assoc. Yes High Yes High link
Ferritin/Iron overload Yes Moderate Weak Low link
Propionic acidemia Yes High None No evidence link
Epilepsy/Seizures Yes Moderate None No evidence link
Uric Acid Weak Low None No evidence link
Electrical Shock Yes Moderate None No evidence link
Liquid Protein Diet Yes High Yes Moderate link
Sickle Cell Disease Yes High Weak Very Low link
Congenital Gen. Lipodystrophy (PTRF) Yes Moderate Weak Very Low link


 

 

Text for citing the use of the QTFactors list or the CredibleMeds.org website:

Woosley, RL; Heise, CW; Gallo, T; Woosley, RD; and Romero, KA
https://crediblemeds.org/ndfa-list/ , QTFactors List, [Accession Date], AZCERT, Inc. 1822 Innovation Park Dr., Oro Valley, AZ 85755