Drug-induced Torsades de Pointes in patients aged 80 years or more/seksen yas ve ustu hastalarda ilaclara bagli Torsades de Pointes.
Objective: We studied all English-written peer-reviewed reports on drug-induced Torsades de Pointes Torsades de pointes or torsades is a French term that literally means "twisting of the points". It was first described by Dessertenne in 1966 and refers to a specific variety of ventricular tachycardia that exhibits distinct characteristics on the (TdP) in patients aged 80 years or more in order to characterize the clinical circumstances leading to this serious complication.
Methods: Our literature search yielded 24 reports on 25 patients aged 80-95 years with drug-induced TdP. We systematically reviewed each report and recorded the non-modifiable risk factors for drug-induced TdP (i.e., female sex and structural heart disease) as well as preventable clinical circumstances, which might have been associated with drug-induced TdP.
Results: The most prevalent risk factors for drug-induced TdP were non-modifiable risk factors: 22 (88%) patients were female patients and 19 (76%) patients had structural heart disease. Overall, 16 (64%) patients were female patients with structural heart disease. The literature did not report any elderly male patients without structural heart disease. Among the preventable clinical circumstances, which might have been associated with drug-induced TdP, the most prevalent were: administrating QT prolonging agents despite long QT interval QT interval
the portion of an electrocardiogram between the onset of the Q wave and the end of the T wave, representing the total time for ventricular depolarization and repolarization. (n=11; 44%) and co-administration of two or more QT prolonging agents (n=9; 36%). The most prevalent QT prolonging agents found to trigger TdP were macrolides and quinolones (n=9; 36%). All but three patients had at least one or more preventable clinical circumstances, which might have been associated with drug-induced TdP.
Conclusion: Physicians should be more aware of the risk for drug-induced TdP in patients aged 80 years or more while administrating QT prolonging agents despite long QT interval and co- administrating two or more QT prolonging agents, specifically in elderly female patients with structural heart disease. (Anadolu Kardiyol Derg 2008; 8. 260-5)
Key words: Nonagenarians, octogenarians, Torsades de Pointes, risk factors
Amac: Biz, 80 yas ve ustu olan hastalarda ciddi komplikasyonlara yol acan ilaclara bagh
A decorative trimming of twisted ribbon or cord, used especially on hats.
[French, from tors, from Vulgar Latin *torsus, alteration of Latin tortus de Pointes'in (TdP) klinik kosullarini tammlamak icin , hakemlik dergilerde Ingilizce yayinlanan t6m calismalari inceledik.
Yointemler: Literaturtaramamiz, 80-95 yaslarinda TdP'li 25vakayi bildiren 24 raporun sonucunu verdi. Her rapor sistematik olarak incelenip ilaca bagh gelisen TdP icin degistirilemeyen risk faktorleri (kadin cinsiyeti ve yapisal kalp hastaligi) ve TdP'le iliskili modifiye edilebilen klinik kosullari kaydedildi.
Bulgular: Ilaclara bagh TdP icin en yaygm risk faktorleri, modifiye edilmeyenler idi; kadin cinsiyeti (%88- 22 hasta) ve yapisal kalp hastaligi (%76, 19 hasta). Toplamda, (%64) 16 kadin hastanin yapisal kalp hastaligi var idi. Literaturde, yapisal kalp hastaligi olmaksizin herhangi bir yasli erkek hasta bildirilmedi. Ilaca bagh TdPes ile iliskilendirilmis, onlenebilir klinik kosullarin arasinda, en yaygm arasinda: Uzun QT araligma ragmen (n= 11; %44) QT araligim uzatan ilaclarm kullanilmasi ve iki veya daha cok QT araligini uzatan ilaclarin kullanilmasi (n= 9; %36) yer almistir. En yaygin olarak TdP'yi tetikleyen QT araligini uzatan ilaclar , makrolidler ve kinolonlar oldugu (n= 9; 36%) saptandi. Uc hasta disinda t6m hastalarda, ilaclara bagh TdP icin bir veya daha fazia onlenebilir klinik kosullari vardi.
Sonuc: Doktorlar, QT araligini uzatan ilaclari 80 yas ve ustu hastalarda, 6zellikle uzun QT araligi olan ve yapisal kalp hastaliklan olan kadin hastalarda kullanirken, ilaclara bagh gelisen TdP'nin riskleri g6z 6n6nde tutmalilar. (Anadolu Kardiyol Derg 2008, 8. 260-5)
Anahtar kelimeler: Doksan ile 99 yaslari arasindaki hastalar, 80 ile 89 yaslari arasindaki hastalar, Torsades de Pointes
Torsades de Pointes (TdP) is a polymorphic ventricular tachycardia Ventricular Tachycardia Definition
Ventricular tachycardia (V-tach) is a rapid heart beat that originates in one of the lower chambers (the ventricles) of the heart. that may lead to ventricular fibrillation ventricular fibrillation
Uncoordinated contraction of the muscle fibres of the heart's ventricles (see arrhythmia). Causes include heart attack, electric shock, anoxia, abnormally high potassium or low calcium in the blood, and digitalis or epinephrine poisoning ( and sudden death. This potentially fatal arrhythmia arrhythmia (ārĭth`mēə), disturbance in the rate or rhythm of the heartbeat. Various arrhythmias can be symptoms of serious heart disorders; however, they are usually of no medical significance except in the presence of is rarely associated with congenital long-QT syndrome and mostly associated with drug administration and electrolyte imbalances. Several antiar rhythmic, anti-infective, anti-psychotic and other agents, might trigger TdP by blocking specific potassium channels in the myocyte membrane. Their effect reduces the outward potassium current called Ikr. Inhibition of this major re-polarizing potassium current participates in prolongation of the action potential in the ventricular myocardium myocardium /myo·car·di·um/ (-kahr´de-um) the middle and thickest layer of the heart wall, composed of cardiac muscle.
hibernating myocardium see myocardial hibernation, under , and this leads to the clinical finding of QT interval prolongation and rarely to TdP (1).
Some patients might exhibit extensive prolongation of the QT interval while taking the above-mentioned drugs. Hence, they might be at risk for drug-induced TdP. Risk factors for drug-induced TdP include: female sex, hypokalemia Hypokalemia Definition
Hypokalemia is a condition of below normal levels of potassium in the blood serum. Potassium, a necessary electrolyte, facilitates nerve impulse conduction and the contraction of skeletal and smooth muscles, including the heart. , recent conversion from atrial fibrillation atrial fibrillation
Irregular rhythm (arrhythmia) of contraction of the atria (upper heart chambers). The most common major arrhythmia, it may result as a consequence of increased fibrous tissue in the aging heart, of heart disease, or in association with severe infection. , congestive heart failure congestive heart failure, inability of the heart to expel sufficient blood to keep pace with the metabolic demands of the body. In the healthy individual the heart can tolerate large increases of workload for a considerable length of time. , baseline QT prolongation, severe hypomagnesaemia, and others (1, 2). Many of these risk factors are common in elderly patients. For example, congestive heart failure affects about 10% of patients aged 75 years or more (3). Additionally, the use of diuretics Diuretics Definition
Diuretics are medicines that help reduce the amount of water in the body.
Diuretics are used to treat the buildup of excess fluid in the body that occurs with some medical conditions such as congestive heart is prevalent in elderly patients. Diuretics might increase the risk for drug-induced TdP by causing hypokalemia and hypomagnesaemia (4, 5). Worldwide, the majority of elderly population is women. Women, elderly in particular, are at an increased risk for drug-induced TdP (1, 6). Moreover, elderly patients might have high offending drug concentrations due to decreased renal clearance renal clearance
The volume of plasma that is completely cleared of a specific compound per unit time, measured as a test of kidney function. , decreased hepatic metabolism hepatic metabolism Therapeutics The constellation of chemical alterations to drugs or metabolites that occur in the liver, carried out by microsomal enzyme systems, which catalyze glucuronide conjugation, drug oxidation, reduction and hydrolysis. See Metabolism. , and polypharmacy-associated hepatic drug interactions (7).
Conventionally, "elderly" has been defined as a chronological age chron·o·log·i·cal age
n. Abbr. CA
The number of years a person has lived, used especially in psychometrics as a standard against which certain variables, such as behavior and intelligence, are measured. of 65 years or more (8). However, approximately one-third of elderly individuals maintain healthy lives late into their 80's and 90's (9). Since this population is expected to grow in the future, it is of great importance to study the clinical circumstances, which might lead to drug-induced TdP in octogenarians and nonagenarians. There are no reviews or clinical studies concerning drug-induced TdP or drug-induced QT prolongation in patients aged 80 years or more.
The aim of the present study is to characterize the clinical circumstances leading to drug-induced TdP in patients aged 80 years or more by systematic analysis of reports published in peer- reviewed journals.
Retrieval of case reports
This was a systematic review. We performed a literature search for all peer-reviewed reports in English on elderly patients aged 80 years or more who were diagnosed as having drug-induced TdP, until May 2008, by using the following keywords in the PubMed: "Torsades de Pointes", "Torsade de Pointes tor·sade de pointes
Paroxysms of ventricular tachycardia in which the electrocardiogram shows a steady undulation in the QRS axis in runs of 5 to 20 beats and with progressive changes in direction. ", "QT", "Arrhythmia", "Syncope syncope
Effect of temporary impairment of blood circulation to a part of the body. It is often used as a synonym for fainting, which is loss of consciousness due to inadequate blood flow to the brain. ", and "Sudden death". The references in each report were further reviewed for additional publications, as were relevant letters to the editor.
Exclusion of case reports
The following reports were excluded: reports on TdP not triggered by drugs; reports on drug-induced TdP in patients aged 79 years or less; reports on sudden death without documented TdP; reports published in non-peer-reviewed journals; reports on suicide attempts with very high doses of QT prolonging agents; reports on polymorphic ventricular tachycardia due to ischemia; and reports on series of patients without a detailed description of every patient.
Non-modifiable risk factors for Torsades de Pointes
Each case report was analyzed for the documented presence of non-modifiable risk factors for drug-induced TdP, i.e., female sex (6) and structural heart disease, including high-degree atrial-ventricular block (i.e., complete atrialventricular block, second degree Mobitz II atria Atria
The heart has four chambers. The right and left atria are at the top of the heart and receive returning blood from the veins. The right and left ventricles are at the bottom of the heart and act as the body's main pumps. l-ventricular block), bifascicular block, congestive heart failure, ischemic heart disease Ischemic heart disease
Insufficient blood supply to the heart muscle (myocardium).
Mentioned in: Myocarditis
ischemic heart disease , left ventricular hypertrophy left ventricular hypertrophy Cardiology Enlargement of the left ventricle often linked to the prolonged hemodynamic stress of CHF, characterized by myocardial cell hypertrophy, ↑ left ventricular wall thickness, ↓ ventricular compliance, ↑ , and valvulopathy (1, 2). History of atrial fibrillation without mention of echocardiographic findings was not consistentwith the definition of structural heart disease, although it might be associated with atrial atrial /atri·al/ (a´tre-al) pertaining to an atrium.
Of or relating to an atrium.
Having to do with the upper chambers of the heart. dilatation dilatation /dil·a·ta·tion/ (dil?ah-ta´shun)
1. the condition, as of an orifice or tubular structure, of being dilated or stretched beyond normal dimensions.
2. the act of dilating or stretching. (10).
Preventable clinical circumstances leading to Torsades de Pointes
Each case report was analyzed for the presence of preventable clinical circumstances, which might have been associated with drug-induced TdP other than the administration of a QT prolonging agent itself. For example: hypokalemia during the administration of a QT prolonging agent (see Table 1 for the complete list). QT prolonging agents were those accepted by the QTdrugs.org Advisory Board to carry a risk of TdP (11). Hypokalemia was defined as potassium serum levels < 3.5 mmol/L (5). Hypocalcemia Hypocalcemia Definition
Hypocalcemia, a low bood calcium level, occurs when the concentration of free calcium ions in the blood falls below 4.0 mg/dL (dL = one tenth of a liter). The normal concentration of free calcium ions in the blood serum is 4.0-6. was defined as calcium serum levels < 8.5 mg/dL (12). Severe hypomagnesaemia was defined as magnesium serum levels < 1 mg/dL (1). Inappropriate or no adjustment of a QT prolonging agent's dosing in patients with reduced creatinine clearance creatinine clearance
The volume of serum or plasma that would be cleared of creatinine by one minute's excretion of urine.
creatinine clearance or reduced hepatic metabolism was defined according to the pharmacokinetics of the offending agent. Digitalis toxicity digitalis toxicity Digoxin toxicity Cardiology Clinical findings of digoxin overdose Clinical Loss of appetite, N&V, defects in color vision–reds and greens, or seeing halos around lights, psychotic changes, weakness, fatigue, or dizziness; new onset of was defined as digitalis digitalis (dĭj'ĭtăl`ĭs), any of several chemically similar drugs used primarily to increase the force and rate of heart contractions, especially in damaged heart muscle. The effects of the drug were known as early as 1500 B.C. serum levels > 2.6 ng/mL (13). Prolonged QT interval in the baseline electrocardiogram electrocardiogram /elec·tro·car·dio·gram/ (-kahr´de-o-gram?) a graphic tracing of the variations in electrical potential caused by the excitation of the heart muscle and detected at the body surface. before drug initiation (4, 14), was defined as corrected QT interval (QTc) > 450 msec for both men and women and was calculated by using the Bazett's formula (15).
Descriptive statistical analysis was performed with SPSS A statistical package from SPSS, Inc., Chicago (www.spss.com) that runs on PCs, most mainframes and minis and is used extensively in marketing research. It provides over 50 statistical processes, including regression analysis, correlation and analysis of variance. (SPSS Inc., Chicago, IL, USA) system for Windows, version 13.0. Continuous variables, such as age and corrected QT interval, were summarized by means, standard deviation In statistics, the average amount a number varies from the average number in a series of numbers.
(statistics) standard deviation - (SD) A measure of the range of values in a set of numbers. , medians and ranges.
Our literature search yielded 24 reports on 25 elderly patients with drug-induced TdP (16-39). Clinical characteristics of reported patients are illustrated in Table 1. Baseline corrected QT interval was reported in 15 patients and their mean corrected QT interval was 449[+ or -]33 msec (median: 450 msec; range: 387-525 msec). Baseline QT interval was reported in three patients (350 msec, 400 msec and 440 msec). Corrected QT interval following the arrhythmia was reported in 13 patients and their mean corrected QT interval was 576[+ or -]83 msec (median: 544 msec; range: 480-720 msec). QT interval following the arrhythmia was reported in 6 patients and their mean QT interval was 531[+ or -]97 msec (median: 560 msec; range: 360-640 msec). All patients survived the potentially fatal arrhythmia.
Incidence of non-modifiable risk factors for Torsade de Pointes
Overall, 22 (88%) patients were females and 19 (76%) patients had structural heart disease (Table 1). Reported were 16 (64%) female patients with structural heart disease, 6 (24%) female patients with no structural heart disease, and 3 (12%) male patients with structural heart disease. Elderly male patients with no structural heart disease were not reported (Table 1). On average, 1.64[+ or -]0.49 non-modifiable risk factors for TdP were observed.
Preventable clinical circumstances leading to Torsades de Pointes
Among the preventable clinical circumstances, which might have been associated with drug-induced TdP, the most prevalent were: administrating QT prolonging agents despite long baseline QT interval or long corrected QT interval (n=11; 44%), co-administration of two or more QT prolonging agents (n=9; 36%), not adjusting QT prolonging agents' doses to the decreased creatinine clearance (n=5; 20%), and hypokalemia during the administration of QT prolonging agents (n=4; 16%). All but three patients were reported to have one preventable clinical circumstance, which might have been associated with drug-induced TdP. Fifteen (60%) patients were reported to have two or more preventable clinical circumstances, which might have been associated with drug-induced TdP (Table 2). On average, 1.8[+ or -]1.1 preventable clinical circumstances associated with drug-induced TdP were observed.
Overall risk factors and clinical circumstances leading to Torsades de Pointes
All the patients had two or more non-modifiable risk factors for TdP and/or preventable clinical circumstances, which might have been associated with drug-induced TdP. Moreover, 15 (60%) patients had four or more non-modifiable risk factors for TdP and/or preventable clinical circumstances, which might have been associated with drug-induced TdP (Fig. 1).
Drugs that triggered Torsades de Pointes
The most prevalent drugs to trigger TdP were macrolides and quinolones (n=9; 36%). The rest of the drugs to trigger TdP were anti arrhythmic ar·rhyth·mic
Lacking rhythm or regularity of rhythm. agents (n=6), psychotropic agents (n=4), anti-histamines (n=3) and terodiline (n=3) (Table 3).
In most nations around the world, the 80-year-old and over age group is rapidly growing. By 2050, this age group is projected to number almost 379 million worldwide - 5.5 times as many as in 2000 (40). As this age group continues to grow, so does its susceptibility to drug-induced TdP, because female gender, congestive con·ges·tive
Of or characterized by congestion.
pertaining to or associated with congestion. See also congestive heart failure. heart disease, diuretics therapy, decreased renal clearance, and decreased hepatic metabolism are all prevalent in these ages (1-7). Since physicians are going to face more of these high-risk patients in the future, it is of great importance to study the clinical circumstances, which might lead to drug-induced TdP in octogenarian oc·to·ge·nar·i·an
Being between 80 and 90 years of age.
A person between 80 and 90 years of age. and older patients.
We sought to study patients aged 80 years or more who had drug-induced TdP while being prescribed with QT prolonging agents. Physicians who prescribe QT prolonging agents should consider drug interactions, hepatic metabolism, renal clearance, electrolyte disturbances, and QT prolongation before and during the treatment. In other words Adv. 1. in other words - otherwise stated; "in other words, we are broke"
put differently , we aimed to study if the physicians who prescribed the QT prolonging agents had been judicious enough with their prescriptions and took all the necessary safety measures safety measures,
n.pl actions (e.g., use of glasses, face masks) taken to protect patients and office personnel from such known hazards as particles and aerosols from high-speed rotary instruments, mercury vapor, radiation exposure, anesthetic and . We found that all but three patients had at least one preventable clinical circumstance, which might have been associated with drug-induced TdP other than the administration of a QT prolonging agent itself. Moreover, 60% of the patients had two or more preventable clinical circumstances which might have been associated with TdP. Administrating QT prolonging agents despite baseline long QT interval, and co-administration of two or more QT prolonging agents, were the two most prevalent preventable clinical circumstances which might have been associated with drug-induced TdP. Hence, we believe that the physicians who had prescribed the QT prolonging agents were not judicious enough in its use.
Overall, 88% of all patients were female patients, 76% of all patients had structural heart disease, and 64% of all patients were female patients with structural heart disease. This observation is consistent with previous reports: female patients have a longer QT interval than male patients (41), they have more pronounced QT prolongation when challenged with potassium channel blockers (42), and they are at a higher risk for developing drug-induced TdP when treated with antiarrhythmic drugs Antiarrhythmic Drugs Definition
Antiarrhythmic drugs are medicines that correct irregular heartbeats and slow down hearts that beat too fast.
Normally, the heart beats at a steady, even pace. or during spontaneous bradyarrhythmias (6). Patients with heart failure have down regulation of potassium channels leading to action potential prolongation (43). Also, left ventricular dilatation is associated with down-regulation of the gap-junction protein connexin43 (44). All these factors significantly increase the duration and the dispersion of repolarization repolarization /re·po·lar·iza·tion/ (re-po?ler-i-za´shun) the reestablishment of polarity, especially the return of cell membrane potential to resting potential after depolarization. to predispose pre·dis·pose
To make susceptible, as to a disease. a given patient to TdP when challenged with a drug that further impairs repolarization. For these reasons, it is well established that elderly female patients and patients with structural heart disease are at increased risk for drug-induced TdP (1).
[FIGURE 1 OMITTED]
Administrating QT prolonging agents despite long baseline QT interval was the most prevalent preventable clinical circumstance, which might have been associated with drug-induced TdP. Moreover, in two reports, QT prolonging agents were continued despite an increasing QT interval. This is not surprising; according to Viskin et al., less than 50% of cardiologists and less than 40% of other physicians can accurately calculate a corrected QT interval, and less than 25% of cardiologists and other physicians can identify a long QT when they see one. Moreover, in the presence of a U wave, many physicians have a difficulty deciding where the T wave ends and the U wave begins (45). It is also difficult to distinguish between a U wave and a biphasic bi·pha·sic
Having two distinct phases: a biphasic waveform; a biphasic response to a stimulus. T wave (46). The absence of down-stroke in the T waves also makes it difficultto measure the QT interval. Due to the diverse spectrum of medications that might trigger TdP (1), and because patients aged 75 years or more take an average of six different medications (47), physicians in all fields of medicine and in geriatrics geriatrics (jĕrēă`trĭks), the branch of medicine concerned with conditions and diseases of the aged. Many disabilities in old age are caused by or related to the deterioration of the circulatory system (see arteriosclerosis), e.g. in particular, should be able to recognize a long QT when they see one. With that emphasized, efforts should be made at all levels of medical education to increase the awareness of prolonged QT interval.
Co-administration of two or more QT prolonging agents, which was present in 36% of the patients, has long been recognized as an important risk factor for drug-induced TdP (1). According to Curtis et al., 22% of outpatients with overlapping prescriptions for two or more QT prolonging agents are elderly (48). Unfortunately, some physicians ignore the "black-box" warning labels made by the pharmaceutical companies, which are attached to these agents. For example, terfenadine was withdrawn from the American market in 1998 following unsuccessful attempts to limit its administration together with other arrhythmogenic agents (49). Since the number of drugs associated with adverse interactions continuously increases, and since polypharmacy is common in the elderly (47), it is not practical to remember all the potential adverse interactions without the aid of computer-generated warnings at the time of drug prescription or drug dispense. In the meanwhile, physicians can find updated information regarding the risk for QT prolongation for a given drug and the risk for drug interactions in the Internet (50).
Limitations of the study
Our study was based on published case reports. We assume that there are many more incidents of drug-induced TdP in patients aged 80 years or more that have not been published; when a similar incidence involving a given agent has already appeared in print several times; when a report is rejected from publication because TdP is attributed to early multiple risk factors for TdP rather than to initiating the offending drug; or when physicians are reluctant to report their deceased patients. Indeed, in all the cases we studied, the patients survived the arrhythmia. Patients with sudden death without documentation of an arrhythmia would also go unrecorded. We believe that our results are, therefore, more likely an underestimation of the true prevalence of clinical circumstances, which might lead to drug-induced TdP in octogenarians and older patients. On the other hand, a control group of younger patients or patients who did not develop TdP was not studied. Hence, we cannot estimate the incidence of TdP in patients aged 80 years or more, or if our findings are implacable to other age groups as well.
According to our findings, the majority of patients aged 80 years or more with drug-induced TdP developed the arrhythmia despite an easily identified clinical circumstance, which might have been associated with drug-induced TdP. We believe that previous recommendations regarding taking measures before prescribing any OT prolonging agent are particularly relevant to patients aged 80 years or more: elderly female patients with structural heart disease should be treated more cautiously (1). Obtaining a baseline electrocardiogram (ECG ECG electrocardiogram.
Also called an electrocardiogram, it records the electrical activity of the heart. ) and another ECG following the first doses of OT prolonging agents are advisable, particularly when prescribing two or more OT prolonging agents, although the efficacy and cost-effectiveness of doing so have not been established. If the corrected OT interval exceeds 450 msec, physicians should avoid prescribing OT prolonging agents or should decrease the OT prolonging agent's dose. It is also advisable to monitor the potassium serum levels frequently, especially in patients treated with diuretics.
Physicians who prescribe OT prolonging agents should consider drug interactions, hepatic metabolism, renal clearance, electrolyte disturbances, and OT prolongation before and during the treatment, especially in patients aged 80 years or more.
(1.) Roden DM. Drug-induced prolongation of the OT interval. N Engl J Med 2004; 350: 1013-22.
(2.) Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, et al. Dofetilide in patients with congestive heart failure and left ventricular dysfunction ventricular dysfunction,
n an abnormality in contraction and wall motion within the ventricles. . N Engl J Med 1999; 341: 857-65.
(3.) Kannel WB, Pinsky JL: Trends in cardiac failure cardiac failure: see congestive heart failure. incidence and causes of three decades in the Framingham study. J Am Coll Cardiol 1991; 17: 87A.
(4.) Taylor SH. Diuretic diuretic (dī'yərĕt`ĭk), drug used to increase urine formation and output. Diuretics are prescribed for the treatment of edema (the accumulation of excess fluids in the tissues of the body), which is often the result of underlying therapy in congestive heart failure. Cardiol Rev 2000; 8: 104-14.
(5.) Kay GN, Plumb VJ, Arciniegas JG, Henthorn RW, Waldo AL. Torsades de pointes: the long-short initiating sequence and other clinical features: observations in 32 patients. J Am Coll Cardiol 1983; 2: 806-17.
(6.) Makkar RR, Fromm BS, Steinman RT, Meissner MD, Lehmann MH. Female gender as a risk factor for torsades de pointes associated with cardiovascular drugs. JAMA JAMA
Journal of the American Medical Association 1993; 270: 2590-7.
(7.) Wade OL. Drug therapy in the elderly. Age Ageing 1972;1: 65-73.
(8.) Orimo H, Ito H, Suzuki T, Araki A, Hosoi T, Sawabe M, et al. Reviewing the definition of "elderly". Geriatrics & Gerontology gerontology: see geriatrics. International 2006; 6: 149-58.
(9.) Depp CA, Jeste DV. Definitions and predictors of successful aging: a comprehensive review of larger quantitative studies. Am J Geriatr Psychiatry 2006;14: 6-20.
(10.) eMedicine: Atrial fibrillation. Available from: http://www.emedicine.com/emerg/topic46.htm. Accessed on the 4th of June, 2007.
(11.) Arizona Center for Education and Research on Therapeutics. http://www.torsades.org/. Accessed on the 4th of June, 2007.
(12.) Napolitano C, Priori SG, Schwartz PJ. Torsades de pointes. Mechanisms and management. Drugs 1994; 47: 51-65.
(13.) eMedicine: Digitalis toxicity. Available from: http://www.emedicine.com/med/topic568.htm. Accessed on the 4th of June, 2007.
(14.) Houltz B, Darpo B, Edvardsson N, Blomstrom P, Brachmann J, Crijns HJGM, et al. Electrocardiographic electrocardiographic
emanating from or pertaining to electrocardiography.
maintenance of a more or less continuous surveillance of a patient's cardiac status by means of electrocardiography. and clinical predictors of torsades de pointes induced by almokalant infusion in patients with chronic atrial fibrillation or flutter: a prospective study. Pacing Clin Electrophysiol 1998; 21: 1044-57.
(15.) Bazzet HC. An analysis of time relations of echocardiograms. Heart 1920; 7: 353-67.
(16.) Bertino JS Jr, Owens RC Jr, Carnes TD, lannini PB. Gatifloxacin-associated corrected OT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors. Clin Infect Dis 2002; 34: 861-3.
(17.) Justo D, Mardi T, Zeltser D. Roxithromycin-induced torsades de pointes. Eur J Intern Med 2004;15: 326-7.
(18.) Samaha FF. OTC OTC
See over-the-counter market (OTC). interval prolongation and polymorphic ventricular tachycardia in association with levofloxacin. Am J Med 1999; 107: 528-9.
(19.) Fteha A, Fteha E, Haq S, Kozer L, Saul B, Kassotis J. Gatifloxacin induced torsades de pointes. Pacing Clin Electrophysiol 2004; 27: 1449-50.
(20.) Sekkarie MA. Torsades de pointes in two chronic renal failure chronic renal failure Chronic kidney failure Nephrology A slow decline in renal function, which may be 2º to chronic HTN, DM, CHF, SLE, or sickle cell anemia and, if extreme, leads to ESRD, mandating kidney dialysis; an abrupt decline in renal function may be patients treated with cisapride and clarithromycin. Am J Kidney Dis 1997; 30: 437-9.
(21.) Goss JE, Ramo BW, Blake K. Torsades de pointes associated with astemizole (Hismanal) therapy. Arch Intern Med 1993; 53: 2705.
(22.) Gitler B, Berger LS, Buffa Buf´fa
n. fem. 1. (Mus.) The comic actress in an opera.
a droll or comic air.
a comic opera. See Opera bouffe. SO. Torsades de pointes induced by erythromycin erythromycin (ĭrĭth'rōmī`sĭn), any of several related antibiotic drugs produced by bacteria of the genus Streptomyces (see antibiotic). . Chest 1994;105: 368-72.
(23.) Connolly MJ, Astridge PS, White EG, Morley CA, Cowan JC. Torsades de pointes ventricular tachycardia and terodiline. Lancet 1991; 338: 344-5.
(24.) Herrmann HC, Kaplan LM, Bierer BE. O-T O-T Observer-Target prolongation and torsades de pointes ventricular tachycardia produced by the tetracyclic antidepressant tet·ra·cy·clic antidepressant
Any of a class of antidepressants whose chemical structure includes four benzene rings. agent maprotiline. Am J Cardiol 1983; 51: 904-6.
(25.) Matsis PP, Easthope RN. Torsades de pointes ventricular tachycardia associated with terfenadine and paracetamol paracetamol
an analgesic and antipyretic drug in dogs. It is contraindicated for cats because of serious side-effects which include intravascular hemolysis, methemoglobinemia and hepatic necrosis. self medication. New Zeeland medical journal 1994; 369: 402-3.
(26.) McLeod AA, Thorogood S. Torsades de pointes complicating treatment with terodiline. Br Med J 1991; 302: 1469.
(27.) Ng KS, Tham LS, Tan HH, Chia BL. Cisapride and torsades de pointes in a pacemaker patient. Pacing Clin Electrophysiol 2000; 23: 130 -2.
(28.) Rezkalla M, Pochop C. Erythromycin induced Torsades de Pointes: case report and review of the literature. S D J Med 1994; 47: 161-4.
(29.) Wilting I, Smals OM, Holwerda NJ, Meyboom RH, de Bruin ML, Egberts TC. QTc prolongation and torsades de pointes in an elderly woman taking fluoxetine fluoxetine /flu·ox·e·tine/ (floo-ok´se-ten) a selective serotonin reuptake inhibitor used as the hydrochloride salt in the treatment of depression, obsessive-compulsive disorder, bulimia nervosa, and premenstrual dysphoric disorder. . Am J Psychiatry 2006;163: 325.
(30.) Tei Y, Morita T, Inoue S, Miyata H. Torsades de pointes caused by a small dose of risperidone in a terminally ill cancer patient. Psychosomatics 2004; 45: 450-1.
(31.) Voigt L, Coromilas J, Saul BI, Kassotis J. Amiodarone-induced Torsades de Pointes during bladder irrigation irrigation, in agriculture, artificial watering of the land. Although used chiefly in regions with annual rainfall of less than 20 in. (51 cm), it is also used in wetter areas to grow certain crops, e.g., rice. : an unusual presentation-a case report. Angiology angiology /an·gi·ol·o·gy/ (an?je-ol´ah-je) the study of the vessels of the body; also, the sum of knowledge relating to the blood and lymph vessels.
n. 2003; 54: 229-31.
(32.) Gowda RM, Punukollu G, Khan IA, Patlola RR, Tejani FH, Cosme-Thormann BF, et al. Ibutilide-induced long QT syndrome The long QT syndrome (LQTS) is a heart condition associated with prolongation of repolarisation (recovery) following depolarisation (excitation) of the cardiac ventricles. It is associated with syncope (fainting) and sudden death due to ventricular arrhythmias. and Torsades de Pointes. Am J Ther 2002; 9: 527-9.
(33.) Chou CC, Wu D. Torsades de pointes induced by metoclopramide in an elderly woman with preexisting pre·ex·ist or pre-ex·ist
v. pre·ex·ist·ed, pre·ex·ist·ing, pre·ex·ists
To exist before (something); precede: Dinosaurs preexisted humans.
v.intr. complete left bundle branch block left bundle branch block Cardiology A condition in which ventricular contraction is not completely synchronized due to a block in conduction of an electrical impulse to the ventricles; in LBBB, right ventricular endocardial activation begins before, and is often . Chang Gung Med J 2001; 24: 805-9.
(34.) Cammu G, Geelen P, Baetens P, De Vos J, Demeyer I. Two cases of torsades de pointes caused by sotalol therapy. Resuscitation resuscitation /re·sus·ci·ta·tion/ (-sus?i-ta´shun) restoration to life of one apparently dead.
cardiopulmonary resuscitation 1999; 40: 49-51.
(35.) Dancey D, Wulffhart Z, McEwan P. Sotalol-induced torsades de pointes in patients with renal failure. Can J Cardiol 1997;13: 55-8.
(36.) Gould LA, Betzu R, Vacek T, Muller RT, Pradeep V, Scafa A. Magnesium treatment of torsades de pointes: a case report. Angiology 1990; 41: 577-81.
(37.) Vorperian VR, Zhou Z, Mohammad S, Hoon hoon Austral & NZ slang
a loutish youth who drives irresponsibly
to drive irresponsibly TJ, Studenik C, January CT. Torsades de pointes with an antihistamine antihistamine (ăn'tĭhĭs`təmēn), any one of a group of compounds having various chemical structures and characterized by the ability to antagonize the effects of histamine. metabolite metabolite, organic compound that is a starting material in, an intermediate in, or an end product of metabolism. Starting materials are substances, usually small and of simple structure, absorbed by the organism as food. : potassium channel blockade with desmethylastemizole. J Am Coll Cardiol 1996; 28: 1556-61.
(38.) Carter JE Jr, Childers RW. Torsades de pointes complicating acute myocardial infarction acute myocardial infarction (·kyōōtˑ mī·ō·karˑ·dē· : the importance of autonomic dysfunction as assessed by heart rate variability Heart rate variability (HRV) is a measure of variations in the heart rate. It is usually calculated by analysing the time series of beat-to-beat intervals from ECG or arterial pressure tracings. . Clin Cardiol 1992; 15: 769-72.
(39.) Kourgiannidis G, Chierchia GB, Wyffels E, Geelen P, Brugada P. A case of monomorphic monomorphic /mono·mor·phic/ (-mor´fik) existing in only one form; maintaining the same form throughout all developmental stages.
mon·o·mor·phic or mon·o·mor·phous
1. ventricular tachycardia? J Cardiovasc Electrophysiol 2005;16: 1014-16.
(40.) World population aging: 1950-2050. Available at: URL URL
in full Uniform Resource Locator
Address of a resource on the Internet. The resource can be any type of file stored on a server, such as a Web page, a text file, a graphics file, or an application program. : http://www.un.org/esa/population/publications/worldageing19502050/ pdf/90chapteriv.pdf. Accessed on the 4th of June, 2007.
(41.) Vincent GM, Timothy KW, Leppert M, Keating M. The spectrum of symptoms and QT intervals in carriers of the gene for the long QT syndrome. N Engl J Med 1992; 327: 846-52.
(42.) Benton RE, Sale M, Flockhart DA, Woosley RL. Greater quinidine-induced QTc interval prolongation in women. Clin Pharmacol Ther 2000; 67: 413-18.
(43.) Tsuji Y, Opthof T, Kamiya K, Yasui K, Liu W, Lu Z, et al. Pacing-induced heart failure causes a reduction of delayed rectifier potassium currents along with decreases in calcium and transient outward currents in rabbit ventricle ventricle /ven·tri·cle/ (ven´tri-k'l) a small cavity or chamber, as in the brain or heart.ventric´ular
ventricle of Arantius the rhomboid fossa, especially its lower end. . Cardiovasc Res 2000; 48: 300-9.
(44.) Dupont H, Timsit JF, Souweine B, Gachot B, Wolff M, Regnier B. Torsades de pointes probably related to sparfloxacin. Eur J Clin Microbiol Infect Dis 1996; 15: 350-1.
(45.) Viskin S, Rosovski U, Sands AJ, Viskin S, Rosovski U, Sands AJ, et al. Inaccurate electrocardiographic interpretation of long QT: the majority of physicians cannot recognize a long QT when they see one. Heart Rhythm 2005; 2: 569-74.
(46.) Viskin S, Zelster D, Antzelevitch C. When u say "U Waves," what do u mean? Pacing Clin Electrophysiol 2004; 27: 145-7.
(47.) Allard J, Hebert R, Rioux M, Asselin J, Voyer L. Efficacy of a clinical medication review on the number of potentially inappropriate prescriptions prescribed for community-dwelling elderly people. CMAJ CMAJ Canadian Medical Association Journal 2001;164: 1291-6.
(48.) Curtis LH, Ostbye T, Sendersky V, Hutchison S, Allen LaPointe NM, Al-Khatib SM, et al. Prescription of QT-prolonging drugs in a cohort of about 5 million outpatients. Am J Med 2003;114: 135-41.
(49.) Burkhart GA, Sevka MJ, Temple R, Honig PK. Temporal decline in filling prescriptions for terfenadine closely in time with those for either ketoconazole ketoconazole /ke·to·co·na·zole/ (ke?to-kon´ah-zol) a derivative of imidazole used as an antifungal agent.
n. or erythromycin. Clin Pharmacol Ther 1997; 61: 93-6.
(50.) Torsades.org [Internet]. Tucson, Arizona and Rockville, Maryland, US: Arizona Center for Education and Research on Therapeutics The Critical Path Institute, [updated 2008 March 25]. Available from: http://www.torsades.org /.
Yael Paran, Noa Mashav, Oren Henis, Michael Swartzon, Yaron Arbel, Dan Justo
Department of Internal Medicine, Tel-Aviv Sourasky Medical Center, Sackler Faculty of Medicine Sackler Faculty of Medicine is a medical school which is part of Tel Aviv University in Tel Aviv, Israel.
It was named after Arthur M. Sackler, a U.S. doctor who made substantial donations to the school. , Tel-Aviv University, Tel-Aviv, Israel
Address for Correspondence/Yazisma Adresi: Dr. Dan Justo, Department of Internal Medicine, Sourasky Medical Center, 6 Weitzman Street, Tel-Aviv 64239, Israel Phone: +972-52-4266739, Fax: 972-9-7408575, E-mail: firstname.lastname@example.org
Note: This article was presented as a poster at Me 341h Intemadonal Congmss on Becuncardiologyin Istanbul June 2007.
Table 1. Clinical characteristics of reported patients Age, year Mean [+ or -] SDs 84.0 [+ or -] 3.8 Hx of cardiomyopathy/LVH n (%) 4 (16) Hx of ischemic heart disease n (%) 5 (20) Hx of congestive heart failure n (%) 9 (36) Hx of high degree atria n (%) 6 (24) 1-ventricular block Hx of Prior TdP/ ventricular n (%) 2 (8) tachycardia CHF- congestive heart failure, Hx- history; LVH left ventricular hypertrophy; TdP- Torsades de Pointes Table 2. Preventable clinical circumstances, which might have been associated with drug-induced TdP and the non-modifiable risk factors for drug-induced UP among the 25 reported patients Preventable clinical circumstances which might have been associated with Number of References drug-induced UP patients, n (%) 16, 18, 22, 23, Administrating QT prolonging 11 (44) 26, 30, 32, agents despite baseline long 33, 36, 38, 39 QT interval 16, 17, 18, 20, Co-administration of two or 9 (36) 21, 23, 25, more QT prolonging agents 27, 33 16, 19, 20, QT prolonging agents' dose not 5 (20) 31, 35 adjusted to creatinine clearance 16, 21, 31, 34 Hypokalemia during QT prolonging 4 (16) agents' administration 26, 27, 33 Administrating QT prolonging 3 (12) agents despite history of TdP 22, 28, 38 Administrating QT prolonging 3 (12) agents during acute myocardial infarction 18, 19 Administrating QT prolonging 2 (8) agents during atrial fibrillation conversion 18, 28 Continuing QT prolonging agents 2 (8) despite QT prolongation 30 QT prolonging agents' dose not 1 (4) adjusted to reduced hepatic metabolism 25 Administrating QT prolonging 1 (4) agents although syncope has not been investigated 31 Digitalis toxicity during the 1 (4) administration of QT prolonging agents Non-modifiable risk factors for drug-induced UP All, except for Female gender 22 (88) 20, 23, 25 All, except for Structural heart disease 19 (76) 19, 21, 26, 27, 30, 39 TdP - Torsades de Pointes Table 3. Drugs that triggered Torsades de Pointes Antibiotic agents Anti-arrhythmics Psychotropic agents Erythromycin (n=4) Sotalol (n=3) Amitryptiline (n=1) Roxithromycin (n=2) Ibutilide (n=1) Haloperidol (n=1) Gatifloxacin (n=2) Quinidine (n=1) Fluoxetine (n=1) Clarithromycin (n=1) Amiodarone (n=1) Risperidone (n=1) Levofloxacin (n=1) Antibiotic agents Anti-histamines Erythromycin (n=4) Astemisol (n=2) Roxithromycin (n=2) Terfanidine (n=1) Gatifloxacin (n=2) Clarithromycin (n=1) Levofloxacin (n=1)