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Prevalence, predictors and clinical implications of prolonged corrected QT in elderly patients with dementia and suspected syncope

Published:October 25, 2018DOI:https://doi.org/10.1016/j.ejim.2018.10.011

      Highlights

      • Evaluation of prevalence of prolonged corrected QT (QTc) in elderly patients with dementia.
      • Identification of variables, including drugs, associated with prolonged QTc interval.
      • Impact of prolonged QTc on one-year mortality and recurrence of syncope.

      Abstract

      Background

      Long QT and use of QT-prolonging drugs are common among older patients receiving polytherapies, but real-world evidence on their impact in clinical practice is controversial. We investigated prevalence, variables associated and clinical implications of prolonged corrected QT (QTc) among patients from the Syncope and Dementia study.

      Methods

      Observational, prospective, multicenter study. Patients≥65 years with dementia and fall suspected for syncope in the previous three months were enrolled. Several clinical variables and the complete list of medications were recorded for each patient. A 12‑lead ECG was obtained and corrected QT was calculated by the Bazett's formula. One-year followup for death and recurrent syncope was performed.

      Results

      Prolonged QTc was observed in 25% of the 432 enrolled patients (mean age 83.3), and was significantly associated with male gender (OR 2.09; 95% CI 1.34–3.26) and diuretics use (OR 1.85; 95% CI 1.18–2.90). At one-year 23.3% of patients died and 30.4% reported at least one recurrent event. Variables associated with one-year mortality were: age, male gender, atrial fibrillation (AF), use of calcium channel blockers and prolonged QTc (OR 1.80; 95% CI 1.01–3.20). Among patients with prolonged QTc a significant interaction for mortality was found with AF. Recurrent events were associated with the use of antiplatelets, cholinesterase.
      inhibitors and antipsychotics, but not with prolonged QTc.

      Conclusions

      We documented a high prevalence of prolonged QTc, that was associated with male gender and diuretics but not with psychoactive medications. Patients with prolonged QTc had higher one-year mortality, that was four-fold increased in those with concomitant AF.

      Keywords

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      References

        • Khan I.A.
        Clinical and therapeutic aspects of congenital and acquired long QT syndrome.
        Am J Med. 2002 Jan; 112: 58-66
      1. Heise W, Romero K, Woosley RL. QTDrugs Lists: AZCERT; 1999. (Available from): http://www.QTdrugs.orgAvailable from: https://crediblemeds.org/.

        • Tisdale J.E.
        • Jaynes H.A.
        • Kingery J.R.
        • Mourad N.A.
        • Trujillo T.B.
        • Overholser B.R.
        • et al.
        Development and validation of a risk score to predict QT interval prolongation in hospitalized patients.
        Circ Cardiovasc Qual Outcomes. 2013 Jul; 6: 479-487
        • Taneja T.
        • Mahnert B.W.
        • Passman R.
        • Goldberger J.
        • Kadish A.
        Effects of sex and age on electrocardiographic and cardiac electrophysiological properties in adults.
        Pacing Clin Electrophysiol PACE. 2001 Jan; 24: 16-21
        • Rautaharju P.M.
        • Mason J.W.
        • Akiyama T.
        New age- and sex-specific criteria for QT prolongation based on rate correction formulas that minimize bias at the upper normal limits.
        Int J Cardiol. 2014 Jul 1; 174: 535-540
        • Mason J.W.
        • Ramseth D.J.
        • Chanter D.O.
        • Moon T.E.
        • Goodman D.B.
        • Mendzelevski B.
        Electrocardiographic reference ranges derived from 79,743 ambulatory subjects.
        J Electrocardiol. 2007 Jul; 40: 228-234
        • Akylbekova E.L.
        • Crow R.S.
        • Johnson W.D.
        • Buxbaum S.G.
        • Njemanze S.
        • Fox E.
        • et al.
        Clinical correlates and heritability of QT interval duration in blacks: the Jackson Heart Study.
        Circ Arrhythm Electrophysiol. 2009 Aug; 2: 427-432
        • Kallergis E.M.
        • Goudis C.A.
        • Simantirakis E.N.
        • Kochiadakis G.E.
        • Vardas P.E.
        Mechanisms, risk factors, and management of acquired long QT syndrome: a comprehensive review.
        ScientificWorldJournal. 2012; 2012: 212178
        • Letsas K.P.
        • Efremidis M.
        • Kounas S.P.
        • Pappas L.K.
        • Gavrielatos G.
        • Alexanian I.P.
        • et al.
        Clinical characteristics of patients with drug-induced QT interval prolongation and torsade de pointes: identification of risk factors.
        Clin Res Cardiol Off J Ger Card Soc. 2009 Apr; 98: 208-212
        • Ungar A.
        • Mussi C.
        • Nicosia F.
        • Ceccofiglio A.
        • Bellelli G.
        • Bo M.
        • et al.
        The “syncope and dementia” study: a prospective, observational, multicenter study of elderly patients with dementia and episodes of “suspected” transient loss of consciousness.
        Aging Clin Exp Res. 2015 Dec; 27: 877-882
        • Ungar A.
        • Mussi C.
        • Ceccofiglio A.
        • Bellelli G.
        • Nicosia F.
        • Bo M.
        • et al.
        Etiology of Syncope and Unexplained Falls in elderly adults with Dementia: Syncope and Dementia (SYD) study.
        J Am Geriatr Soc. 2016 Aug; 64: 1567-1573
        • Diagnostic and Statistical Manual of Mental Disorders
        Text Revision.
        4th Ed. American Psychiatric Association, Washington, DC2000
        • Bazett H.C.
        An analysis of time relations of electrocardiograms.
        Heart. 1920; 7: 353-367
        • Darbar D.
        • Kimbrough J.
        • Jawaid A.
        • McCray R.
        • Ritchie M.D.
        • Roden D.M.
        Persistent atrial fibrillation is associated with reduced risk of torsades de pointes in patients with drug-induced long QT syndrome.
        J Am Coll Cardiol. 2008 Feb 26; 51: 836-842
        • Wagner G.S.
        • Macfarlane P.
        • Wellens H.
        • Josephson M.
        • Gorgels A.
        • Mirvis D.M.
        • et al.
        AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part VI: acute ischemia/infarction: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society. Endorsed by the International Society for Computerized Electrocardiology.
        J Am Coll Cardiol. 2009 Mar 17; 53: 1003-1011
        • Linn B.S.
        • Linn M.W.
        • Gurel L.
        Cumulative illness rating scale.
        J Am Geriatr Soc. 1968 May; 16: 622-626
        • Conwell Y.
        • Forbes N.T.
        • Cox C.
        • Caine E.D.
        Validation of a measure of physical illness burden at autopsy: the Cumulative Illness Rating Scale.
        J Am Geriatr Soc. 1993 Jan; 41 (Linn BS, Linn MW, Gurel): 38-41
      2. WHOCC - Guidelines for ATC classification and DDD assignment. Available from: https://www.whocc.no/news/guidelines_for_atc_classification_and_ddd_assignment

        • Isbister G.K.
        • Page C.B.
        Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice.
        Br J Clin Pharmacol. 2013 Jul; 76: 48-57
        • Pasquier M.
        • Pantet O.
        • Hugli O.
        • Pruvot E.
        • Buclin T.
        • Waeber G.
        • et al.
        Prevalence and determinants of QT interval prolongation in medical inpatients.
        Intern Med J. 2012 Aug; 42: 933-940
        • Maison O.
        • de la Gastine B.
        • Dayot L.
        • Goutelle S.
        Prevalence and Risk Factors of Drug-Associated Corrected QT Prolongation in elderly Hospitalized patients: results of a Retrospective Analysis of Data Obtained over 6 months.
        Drugs Aging. 2017 Jul; 34: 545-553
        • Vandael E.
        • Vandenberk B.
        • Vandenberghe Willems R.
        • Foulon V.
        Risk factors for QTc-prolongation: systematic review of the evidence.
        Int J Clin Pharmacol. 2017 Feb; 39: 16-25
        • Schächtele S.
        • Tümena T.
        • Gaßmann K.G.
        • Fromm M.F.
        • Maas R.
        Co-Prescription of QT-Interval Prolonging drugs: an Analysis in a large Cohort of Geriatric patients.
        PloS One. 2016; 11e0155649
        • Rabkin S.W.
        Impact of Age and sex on QT Prolongation in patients Receiving Psychotropics.
        Can J Psychiatry Rev Can Psychiatr. 2015 May; 60: 206-214
        • Zhang Y.
        • Ouyang P.
        • Post W.S.
        • Dalal D.
        • Vaidya D.
        • Blasco-Colmenares E.
        • et al.
        Sex-steroid hormones and electrocardiographic QT-interval duration: findings from the third National Health and Nutrition Examination Survey and the Multi-Ethnic Study of Atherosclerosis.
        Am J Epidemiol. 2011 Aug 15; 174: 403-411
        • Charbit B.
        • Christin-Maître S.
        • Démolis J.L.
        • Soustre E.
        • Young J.
        • Funck-Brentano C.
        Effects of testosterone on ventricular repolarization in hypogonadic men.
        Am J Cardiol. 2009 Mar 15; 103: 887-890
        • Bidoggia H.
        • Maciel J.P.
        • Capalozza N.
        • Mosca S.
        • Blaksley E.J.
        • Valverde E.
        • et al.
        Sex differences on the electrocardiographic pattern of cardiac repolarization: possible role of testosterone.
        Am Heart J. 2000 Oct; 140: 678-683
        • Sohaib S.M.A.
        • Papacosta O.
        • Morris R.W.
        • Macfarlane P.W.
        • Whincup P.H.
        Length of the QT interval: determinants and prognostic implications in a population-based prospective study of older men.
        J Electrocardiol. 2008 Dec; 41: 704-710
        • Singh B.N.
        • Hollenberg N.K.
        • Poole-Wilson P.A.
        • Robertson J.I.
        Diuretic-induced potassium and magnesium deficiency: relation to drug-induced QT prolongation, cardiac arrhythmias and sudden death.
        J Hypertens. 1992 Apr; 10: 301-316
        • Brouillette J.
        • Nattel S.
        A Practical Approach to avoiding Cardiovascular adverse Effects of Psychoactive Medications.
        Can J Cardiol. 2017 Dec; 33: 1577-1586
        • Beach S.R.
        • Celano C.M.
        • Noseworthy P.A.
        • Januzzi J.L.
        • Huffman J.C.
        QTc prolongation, torsades de pointes, and psychotropic medications.
        Psychosomatics. 2013 Feb; 54: 1-13
        • Nielsen J.
        • Graff C.
        • Kanters J.K.
        • Toft E.
        • Taylor D.
        • Meyer J.M.
        Assessing QT interval prolongation and its associated risks with antipsychotics.
        CNS Drugs. 2011 Jun 1; 25: 473-490
        • Bouvy J.C.
        • Koopmanschap M.A.
        • Shah R.R.
        • Schellekens H.
        The cost-effectiveness of drug regulation: the example of thorough QT/QTc studies.
        Clin Pharmacol Ther. 2012 Feb; 91: 281-288
        • Riad F.S.
        • Davis A.M.
        • Moranville M.P.
        • Beshai J.F.
        Drug-Induced QTc Prolongation.
        Am J Cardiol. 2017 Jan 15; 119: 280-283
        • Warnier M.J.
        • Rutten F.H.
        • Souverein P.C.
        • de Boer A.
        • Hoes A.W.
        • De Bruin M.L.
        Are ECG monitoring recommendations before prescription of QT-prolonging drugs applied in daily practice? The example of haloperidol.
        Pharmacoepidemiol Drug Saf. 2015 Jul; 24: 701-708
        • Pickham D.
        • Helfenbein E.
        • Shinn J.A.
        • Chan G.
        • Funk M.
        • Weinacker A.
        • et al.
        High prevalence of corrected QT interval prolongation in acutely ill patients is associated with mortality: results of the QT in Practice (QTIP) study.
        Crit Care Med. 2012 Feb; 40: 394-399
        • Nakanishi S.
        • Yamada M.
        • Hattori N.
        • Suzuki G.
        Relation between QT duration and mortality in an elderly Japanese population.
        Am J Cardiol. 2004 May 1; 93: 1182-1185
        • Yap J.
        • Jin A.Z.
        • Nyunt S.Z.
        • Ng T.P.
        • Richards A.M.
        • Lam C.S.
        Longitudinal Community-based Study of QT Interval and Mortality in Southeast Asians.
        PloS One. 2016; 11e0154901
        • De Bruyne M.C.
        • Hoes A.W.
        • Kors J.A.
        • Hofman A.
        • van Bemmel J.H.
        • Grobbee D.E.
        Prolonged QT interval predicts cardiac and all-cause mortality in the elderly. The Rotterdam Study.
        Eur Heart J. 1999 Feb; 20: 278-284
        • Straus S.M.J.M.
        • Kors J.A.
        • De Bruin M.L.
        • van der Hooft C.S.
        • Hofman A.
        • Heeringa J.
        • et al.
        Prolonged QTc interval and risk of sudden cardiac death in a population of older adults.
        J Am Coll Cardiol. 2006 Jan 17; 47: 362-367
        • Odutayo A.
        • Wong C.X.
        • Hsiao A.J.
        • Hopewell S.
        • Altman D.G.
        • Emdin C.A.
        Atrial fibrillation and risks of cardiovascular disease, renal disease, and death: systematic review and meta-analysis.
        BMJ. 2016 Sep 6; 354i4482
        • Sagie A.
        • Larson M.G.
        • Goldberg R.J.
        • Bengtson J.R.
        • Levy D.
        An improved method for adjusting the QT interval for heart rate the Framingham Heart Study.
        Am J Cardiol. 1992; 70: 797-801
        • Sri-On J.
        • Tirrell G.P.
        • Bean J.F.
        • Lipsitz L.A.
        • Liu S.W.
        Revisit, subsequent Hospitalization, Recurrent fall, and death within 6 months after a fall among elderly Emergency Department patients.
        Ann Emerg Med. 2017 Oct; 70: 516-521.e2
        • Carpenter C.R.
        • Avidan M.S.
        • Wildes T.
        • Stark S.
        • Fowler S.A.
        • Lo A.X.
        Predicting geriatric falls following an episode of emergency department care: a systematic review. Acad Emerg Med off J Soc.
        Acad Emerg Med. 2014 Oct; 21: 1069-1082
        • Pasqualetti G.
        • Calsolaro V.
        • Bini G.
        • Dell'Agnello U.
        • Tuccori M.
        • Marino A.
        • et al.
        Clinical differences among the elderly admitted to the emergency department for accidental or unexplained falls and syncope.
        Clin Interv Aging. 2017; 12: 687-695
        • García-Fuertes D.
        • Villanueva-Fernández E.
        • Crespín-Crespín M.
        Drug-induced long-QT and torsades de pointes in elderly polymedicated patients.
        Arq Bras Cardiol. 2016 Feb; 106: 156-159