Prolonged QT predicts prognosis in COVID-19.

BACKGROUND: Coronavirus disease-2019 (COVID-19) causes severe illness and multi-organ dysfunction. An abnormal electrocardiogram is associated with poor outcome, and QT prolongation during the illness has been linked to pharmacological effects. This study sought to investigate the effects of the COVID-19 illness on the corrected QT interval (QTc). METHOD: For 293 consecutive patients admitted to our hospital via the emergency department for COVID-19 between 01/03/20 -18/05/20, demographic data, laboratory findings, admission electrocardiograph and clinical observations were compared in those who survived and those who died within 6 weeks. Hospital records were reviewed for prior electrocardiograms for comparison with those recorded on presentation with COVID-19. RESULTS: Patients who died were older than survivors (82 vs 69.8 years, p < 0.001), more likely to have cancer (22.3% vs 13.1%, p = 0.034), dementia (25.6% vs 10.7%, p = 0.034) and ischemic heart disease (27.8% vs 10.7%, p < 0.001). Deceased patients exhibited higher levels of C-reactive protein (244.6 mg/L vs 146.5 mg/L, p < 0.01), troponin (1982.4 ng/L vs 413.4 ng/L, p = 0.017), with a significantly longer QTc interval (461.1 ms vs 449.3 ms, p = 0.007). Pre-COVID electrocardiograms were located for 172 patients; the QTc recorded on presentation with COVID-19 was longer than the prior measurement in both groups, but was more prolonged in the deceased group (448.4 ms vs 472.9 ms, pre-COVID vs COVID, p < 0.01). Multivariate Cox-regression analysis revealed age, C-reactive protein and prolonged QTc of >455 ms (males) and >465 ms (females) (p = 0.028, HR 1.49 [1.04-2.13]), as predictors of mortality. QTc prolongation beyond these dichotomy limits was associated with increased mortality risk (p = 0.0027, HR 1.78 [1.2-2.6]). CONCLUSION: QTc prolongation occurs in COVID-19 illness and is associated with poor outcome.

Current practices of Asia-Pacific cardiologists in the utilization of bioresorbable scaffolds.

BACKGROUND & AIMS: Although Absorb Bioresorbable Vascular Scaffolds (A-BVS) are routinely used in the Asia-Pacific, there is little information on patient selection or deployment technique here. This document investigates the experiences of leading interventional cardiologists from the Asia-Pacific region with a focus on patient characteristics, deployment techniques and management. METHODS AND RESULTS: A detailed questionnaire was distributed to 28 highly-experienced interventional cardiologists ('Authors') from 13 Asia-Pacific countries. The results were discussed at a meeting on patient selection, technical consideration, deployment practices and patient management. Potential patient benefits of Absorb compared to metallic DES, the learning curve for patient selection and preparation, device deployment, and subsequent patient management approaches are presented. CONCLUSIONS: Current practices are derived from guidelines optimized for European patients. Differences in approach exist in the Asia-Pacific context, including limited access to imaging and frequency of occurrence of complex lesions. Nevertheless, the use of the Absorb BVS ('Absorb') in certain Asia-Pacific countries has flourished and practices here are continuing to mature.

P-wave abnormality predicts recurrence of atrial fibrillation after electrical cardioversion: a prospective study.

BACKGROUND: Maintenance of atrial fibrillation (AF) is related to atrial electrical inhomogeneity and resultant chaotic reentry. Our aim was to test the hypothesis that abnormalities of P morphology on the surface electrocardiogram (ECG) predict recurrent AF following electrical cardioversion (ECV). METHODS: A 12-lead ECG was recorded after ECV for persistent AF in 77 patients (51 men, 65 ± 10 years) and repeated 1 month later. P-wave duration was obtained in each lead using blinded on-screen measurement. Maximum P-wave duration (P-max) was defined as the longest measurable P-wave duration in any lead. P-wave dispersion (PWd) was calculated as the maximum-minimum P-wave duration. RESULTS: One month after ECV, 29 (38%) patients maintained sinus rhythm. Compared with the sinus rhythm group, those with recurrent AF had significantly greater PWd (66 ± 19 vs 57 ± 16 ms, P = 0.024) and included more patients with P-max ≥142 ms (65% vs 38%, P = 0.023). Using a cutoff of ≥62 ms for PWd and ≥142 ms for P-max, both indices had similar predictive value (sensitivity 66.7 and 64.6%, specificity 58.6 and 62.1%, respectively). In multiple regression analysis, including established clinical predictors, P-max ≥142 ms was the only independent predictor of AF recurrence (P = 0.025). CONCLUSION: A prolonged P-wave duration measured by 12-lead ECG predicts recurrent AF within 1 month after ECV.

T-wave alternans and left ventricular wall thickness in predicting arrhythmic risk in patients with hypertrophic cardiomyopathy.

BACKGROUND: Regional heterogeneity of left ventricular (LV) hypertrophy may contribute to arrhythmic vulnerability in patients with hypertrophic cardiomyopathy (HCM). The aim of the present study was to investigate the relationship between LV wall thickness (LVWT) and microvolt T-wave alternans (TWA), a surrogate risk marker of ventricular tachyarrhythmias (VTAs). METHODS AND RESULTS: A total of 157 consecutive HCM patients underwent 2-D echocardiography and TWA-exercise testing, and assessment of arrhythmic burden in a follow up of a median 3.7 years. VTAs were commoner in the non-negative groups (NN-TWA: n=72, TWA+ and indeterminate outcome; 29 events, P<0.02; TWA+: n=34; 14 events, P=0.01), than in the negative TWA group (n=85, 16 events). TWA+ patients were older (P<0.04) and had greater maximal LVWT and LV mass (P=0.02 and P=0.05, respectively), whereas NN-TWA linked only with increased LV mass (P=0.05). Regionally, the TWA+ group had greater inferior LVWT (P<0.05). TWA+ outcome positively correlated with maximal LVWT (r=0.2, P=0.05), and basal/equatorial/apical inferior LVWT (BA6: r=0.2, P=0.05 and EQ6: r=0.2 P=0.03, AP6: r=0.2, P=0.04). Multivariate analysis identified left atrium size, max LVWT and EQ6 with predictive association for TWA+ outcome. CONCLUSIONS: Positive and NN-TWA outcomes are associated with increased LV mass. Moreover, TWA+ is associated with maximal and regional LVWT in HCM patients at risk of arrhythmic events. The present findings support the complementary role of key regional LVWTs in a risk stratification model.

Significance of maximal and regional left ventricular wall thickness in association with arrhythmic events in patients with hypertrophic cardiomyopathy.

BACKGROUND: Increased maximal left ventricular wall thickness (LVWT; >30 mm) is a marker of risk for sudden cardiac death in hypertrophic cardiomyopathy (HCM). Patients with mild left ventricular hypertrophy (LVH) are not free of events. Regional heterogeneity of LVH may contribute to arrhythmic vulnerability. METHODS AND RESULTS: 157 HCM patients underwent assessment of maximal and regional LVWT by 2-dimensional echocardiography, and arrhythmic burden in a follow-up of a median 3.7 years. 45 patients with ventricular arrhythmic events (VAEs+ group) had larger maximal LVWT and regional LVWTs (basal anterior-B12 and equatorial inferior-EQ6 segments, P=0.05). Maximal LVWT and B12 above a cut-off value of 15 mm were associated with a significant 4.5-fold (95% confidence interval (CI) 1.1-18.8, P=0.04), 3.2-fold (95%CI 1.5-6.7, P<0.002), and EQ6 above 19 mm with 5.9-fold (95%CI 2.0-16.9, P<0.001) increased the relative risk of VAEs. Multivariate analysis identified the 2 regional measures as the only predictors, independently associated with arrhythmic risk. CONCLUSIONS: Non-invasive imaging measures, such as LVWT, do have a role in identifying the patients at risk of VAEs. In addition to maximal LVWT, the key regional LVWTs provide complementary information of incremental value to the conventional risk stratification model.

Variation in the prevalence, awareness, and control of diabetes in a multiethnic population: a nationwide population study in Malaysia.

The purpose of this study was to determine the association between different ethnic groups and the prevalence, awareness, and control of diabetes in Malaysia. A population-based cross-sectional study using multistage sampling was conducted in Malaysia. Diabetes is defined as having a fasting blood glucose > or =7 mmol/L or a self-reported diabetic on treatment. Among the 7683 respondents aged > or =30 years, the prevalence of diabetes mellitus was 15.2% (95% CI = 14.1, 16.4). Multivariate analysis showed that compared with Malays, Chinese had lower odds (adjusted odds ratio [aOR] 0.71; 95% CI = 0.56, 0.91) and Indians had higher odds of having diabetes (aOR 1.54; 95% CI = 1.20, 1.98). The odds of diabetes increased with age, family history of diabetes, body mass index, and lower education levels. Among those with diabetes mellitus, 45.0% were aware and 42.7% were under treatment. Among treated diabetics, 25.1% had their fasting blood sugar under control. There is a significant association between prevalence of diabetes and different ethnic groups.

Drug-induced Brugada syndrome.

Brugada syndrome is an inherited cardiac arrhythmia condition characterized by (i) coved ST-elevation and J point elevation of at least 2 mm in at least two of the right precordial ECG leads (V1-V3) and (ii) ventricular arrhythmias, syncope, and sudden death. Patients with Brugada syndrome or suspected mutation carriers can have normal ECG recordings at other times. In these cases, a diagnostic challenge with a sodium channel blocker such as ajmaline, flecainide, or pilsicainide may induce the full-blown type 1 ECG pattern and support the diagnosis. However, recently, many other pharmacological agents not related to class I anti-arrhythmic agents have been reported to induce Brugada ECG patterns including tricyclic antidepressants, fluoxetine, lithium, trifluoperazine, antihistamines, and cocaine. As published reports of the drug-induced Brugada sign have become increasingly prevalent, there is growing interest in the mechanisms responsible for this acquired ECG pattern and its clinical significance. It is possible that drug-induced Brugada syndrome may be due to an individual susceptibility that favours drug-induced ECG abnormalities, possibly as a result of an increase in a latent ion channel dysfunction similar to that in drug-induced long QT syndrome. However, further evidence is needed to confirm this postulation. In this paper, we will review the cases and evidence of drug-induced Brugada syndrome reported in the literature.

Potential demographic and baselines variables for risk stratification of high-risk post-myocardial infarction patients in the era of implantable cardioverter-defibrillator--a prognostic indicator.

BACKGROUND: Risk stratification after myocardial infarction (MI) remains expensive and disappointing. We designed a prognostic indicator using demographic information to select patients at risk of dying after MI. METHOD AND RESULTS: We combined individual patient data from the placebo arms of EMIAT, CAMIAT, TRACE and DIAMOND-MI with LVEF 10 ventricular premature beats/hour or a run of ventricular tachycardia). Risk factors for mortality beginning at day 45 post-MI up to 2 years were examined using Cox regression analysis. Risk scores were derived from the equation of a Cox regression model containing only significant variables. The prognostic index was the sum of the individual contribution from the risk factors. 2707 patients were pooled (age: 66 (23-92) years, 78.8% M) with 480 deaths at 2-years (44% arrhythmic and 35.6% non-arrhythmic cardiac deaths). Variables predicting mortality were age, sex, previous MI or angina, hypertension, diabetes, systolic blood pressure, heart rate, NYHA functional class and non-Q wave infarct on electrocardiogram. Distinct survival curves were obtained for 3 risk groups based on the median and inter-quartile range for the prognostic index. In the high-risk group, up to 40% of patients died (all-cause mortality), 19.1% died of arrhythmic and 18.2% died of non-arrhythmic cardiac causes at 2-years. CONCLUSION: In post-MI patients with LVEF

Arrhythmic complications of electrical cardioversion: relationship to shock energy.

BACKGROUND: Existing guidelines for electrical cardioversion (ECV) of atrial arrhythmias suggest starting at a low energy setting on the grounds that shocks of high energy might damage the myocardium or trigger more serious arrhythmias. We hypothesised that more powerful shocks would exceed the upper limit of vulnerability for inducing ventricular fibrillation. The initial use of higher energy could therefore reduce arrhythmic complications. METHODS: We collected data on the sequence of shocks delivered and the resulting changes in cardiac rhythm in 1896 patients who underwent transthoracic ECV. Rhythm strips derived from 200 consecutive ECV attempts were studied to verify the accuracy of the synchronisation of the shocks delivered. RESULTS: In 2522 attempts at transthoracic ECV, 6398 shocks were delivered, 1243 in atrial flutter or atrial tachycardia, the others in AF. Ventricular fibrillation was significantly more common after shocks of < 200 J (5 of 2959 vs. 0 of 3439 shocks, p<0.05, Fischer's exact test). Conversion of atrial flutter or atrial tachycardia to AF was also more common at < 200 J (20 of 930 shocks vs. 1 of 313 shocks at > or = 200 J, p<0.05, chi2 test). Sinus bradycardia or sinus arrest complicated 0.95% of cardioversion attempts, but none required emergency pacing. The incidence of bradycardia was not related to the energy used. CONCLUSIONS: Shocks of > 200 J are associated with fewer tachyarrhythmic complications, and do not increase the risk of other serious complications. Bradycardia after cardioversion is very rarely of clinical importance.

Sudden cardiac death

Sudden cardiac death (SCD) continues to be a major health issue in many countries including Malaysia due to its large magnitude in all-cause mortality as well as the emotional and socioeconomic impact of the deceased leaving the love ones behind in an abrupt manner. Data in Malaysia shows that the majority of sudden natural deaths are due to sudden cardiac death and are in the productive age group of 41 to 50 years. A study in Germany pointed out that about 90% people who died of SCD actually had warning signs such as chest pain, breathlessness, nausea, vomiting, dizziness and fainting before they collapsed. The majority belonged to the high-risk group for SCD having had previous medical histories including coronary artery disease, cardiomyopathies, valvular heart disease, congenital heart disease, underlying electrophysiological abnormalities or are taking drugs which are capable of provoking ventricular tachyarrhythmias. The key step is to define a sequence of risk stratifiers that will identify patients who are at risk but in whom implantation of expensive devices will be cost-effective. Amongst the investigative tools proven to be helpful to achieve this are ECG screening for left ventricular hypertrophy, increased QRS width, T-wave alternans, heart rate variability, baroreceptor responsiveness, QT dispersion, and T-wave heterogeneity; Holter monitoring to demonstrate ventricular arrhythmias; and stress test in identifying ischaemia. Prompt action is crucial since restoring circulation as fast as possible improves the chances of survival. Family members and caregivers of people with heart disease and at increased risk should be trained to recognize symptoms and perform cardiopulmonary resuscitation (CPR) to reduce the likelihood of death from cardiac arrest. Training and prevention efforts should focus on how to recognize the emergency, CPR training, and automated external defibrillator (AED) use. An implantable cardioverter-defibrillator (ICD) is the preferred therapeutic modality in most survivors of SCD. The incidence of SCD can be reduced by improving the current situation through selection of high risk groups for initiation of therapies, education to the public awareness of early warning symptoms and early emergency management that should be readily available in the community.

Electrocardiographic markers of structural heart disease and predictors of death in 2332 unselected patients undergoing outpatient Holter recording.

AIMS: To test the hypothesis that the QS interval of ventricular ectopic beats (VEBs) (ventricular ectopic QS interval, VEQSI) would provide a marker for the presence of structural heart disease and a predictor of mortality. METHODS AND RESULTS: We interviewed and examined 2332 patients undergoing Holter ECG monitoring for clinical indications. In persons with VEBs, the morphologies were counted and the QS interval was measured for each of these morphologies. The duration of the broadest VEB, measured from the QRS onset in the derivation showing the earliest onset to its end in the derivation showing the latest termination, was taken as that patient's VEQSI. Survival was ascertained from public health records. Of 15 electrocardiographic variables pre-selected as potential prognostic indicators, VEQSI demonstrated the strongest association with the presence of structural heart disease (P = 0.013). Thirty-four persons died in 16 +/- 4 months follow-up. Univariate predictors of mortality are age, history of myocardial infarction, maximum heart rate, QS interval, the number of VEB morphologies, and the VEQSI. On multivariate analysis, only age (P < 0.001) and the number of VEB morphologies (P = 0.02) predicted mortality. CONCLUSION: VEQSI predicts the presence of structural heart disease. The number of VEB morphologies in a Holter recording predicts all-cause mortality.

Optimising the dichotomy limit for left ventricular ejection fraction in selecting patients for defibrillator therapy after myocardial infarction.

BACKGROUND: The selection of patients for prophylactic implantable cardioverter-defibrilator (ICD) treatment after myocardial infarction (MI) remains controversial. AIM: To determine the optimum left ventricular ejection fraction (LVEF) dichotomy limit for ICD treatment in patients with a history of MI. METHODS AND RESULTS: Data from the placebo arms of four randomised trials were pooled to create a cohort of 2828 patients (2206 men, mean (SD) age 65 (11) years) with reduced left ventricular function after MI. The median LVEF was 33% (range 6-40%). LVEF significantly predicted mortality. Each 10% reduction in LVEF <40% conferred a 42% increase in all-cause mortality, a 39% increase in arrhythmic cardiac mortality and a 49% increase in non-arrhythmic cardiac mortality over the 2-year period of follow-up (p<0.001 for all modes of mortality). As the LVEF progressively decreased from < or =40% to < or =10%, the data show a U-shaped relationship between the dichotomy limit for LVEF used and the number of patients who must be treated to prevent one arrhythmic death in 2 years. At an LVEF of 16-20%, more patients are likely to die from arrhythmic than non-arrhythmic cardiac deaths, whereas in those with LVEF < or =10% all deaths were non-arrhythmic. However, the total number of deaths substantially decreased with lower LVEF. CONCLUSION: A trade-off exists between the sensitivity and positive predictive accuracy across a range of LVEF, and no single dichotomy limit is completely satisfactory. In patients with LVEF < or =10% ICD treatment was not beneficial as all patients in this subgroup died from non-arrhythmic causes. The use of a single dichotomy limit for LVEF alone is not sufficient in selecting patients for ICD treatment in the primary prevention of cardiac arrest.

Prognostic value of blood pressure measured during hospitalization after acute myocardial infarction: an insight from survival trials.

BACKGROUND: The prognostic value of blood pressure measured during hospitalization after acute myocardial infarction (MI) has not been investigated, particularly with regard to arrhythmic death. METHODS: A total of 3311 placebo patients (2612 men, median age 64 years; range 23-92) from the EMIAT, CAMIAT, SWORD, TRACE and DIAMOND-MI studies with left ventricular ejection fraction less than 40% or asymptomatic ventricular arrhythmia surviving more than 45 days after MI were pooled. Systolic and diastolic blood pressures and pulse pressures were measured soon after MI (median 6 days, range 0-53 days). Mortality up to 2 years was examined using Cox regression. RESULTS: At the 2-year follow-up, after adjustment for age, sex, smoking, previous MI, hypertension, heart rate, New York Heart Association functional class, baseline treatments, study effect and diastolic blood pressure, reduced systolic blood pressure measured during hospitalization after acute MI significantly increased the risk of all-cause mortality [hazard ratio (HR) for 10% increase in systolic blood pressure 0.80, 95% confidence interval (CI) 0.71-0.90; P < 0.001] and arrhythmic mortality (HR 0.73, 95% CI 0.61-0.86; P = 0.001). Reduced diastolic blood pressure significantly increased the risk of all-cause mortality (HR 0.87, 95% CI 0.77-0.98; P = 0.02) and arrhythmic mortality (HR 0.80, 95% CI 0.68-0.93; P = 0.005). CONCLUSION: In post-MI patients with left ventricular ejection fraction less than 40% or asymptomatic ventricular arrhythmia, reduced blood pressure measured during hospitalization after MI significantly predicts all-cause mortality and arrhythmic mortality, and can be reliably used to identify patients who are at risk of dying after MI.

Distribution and prognostic significance of QT intervals in the lowest half centile in 12,012 apparently healthy persons.

The presence of an abnormally short QT interval has been noted among survivors of idiopathic ventricular fibrillation and among close relatives of victims of unexplained sudden death. Most reported cases have had rate-corrected QT (QTc) intervals of <300 ms. The prevalence of such values in the community has not been documented. We reviewed the electrocardiograms (ECGs) of 12,012 subjects who underwent routine medical examinations for occupational reasons. The QT interval was measured by 2 physicians in all cases, and QTc interval was calculated. All ECGs with QTc values in the lowest 5% were reviewed by 2 cardiologists expert in QT analysis, and the QT measurement was corrected if necessary. Information about subsequent survival was obtained from the case file or from public records. In the lowest 1/2 centile, the distribution of QTc values continued to follow a normal pattern without evidence of a distinct subpopulation of low values. The shortest QTc encountered was 335 ms. Information about subsequent survival was available for 36 of the 60 subjects with the lowest 1/2 centile of QTc values. None of these subjects died during the 7.9 +/- 4.5 years subsequent to the ECG that demonstrated the short QT interval. In conclusion, a QTc interval of

Prognostic impact of demographic factors and clinical features on the mode of death in high-risk patients after myocardial infarction--a combined analysis from multicenter trials.

BACKGROUND: Contemporary information is lacking on the effect of demographic features and clinical features on the specific mode of mortality after myocardial infarction (MI) in the thrombolytic era. HYPOTHESIS: The aims of this study were (1) to examine the risk and trend of a different mode of mortality (i.e., all-cause, arrhythmic, and nonarrhythmic cardiac mortality) in high-risk patients post MI with reduced left ventricular ejection fraction (LVEF) or ventricular arrhythmias; and (2) to assess the predictive value of demographic and clinical variables in the prediction of specific modes of death in high-risk patients post MI in the thrombolytic era. METHODS: In all, 3,431 patients receiving placebo (2,700 men, median age 64 +/- 11 years) from the EMIAT, CAMIAT, SWORD, TRACE, and DIAMOND-MI studies, with LVEF < 40% or ventricular arrhythmia were pooled. Risk factors for mortality among patients surviving > or = 45 days after MI up to 2 years were examined using Cox regression. Short-term survival (from onset of MI to Day 44 after MI) was also examined for TRACE and DIAMOND-MI, in which patients were recruited within 2 weeks of MI. RESULTS: After adjustment for treatment and study effects, age, previous MI/angina, increased heart rate, and higher New York Heart Association functional class increased the risk of all-cause, arrhythmic, and cardiac mortality. Male gender, history of hypertension, low baseline systolic blood pressure, and Q wave were predictive of all-cause and arrhythmic mortality, whereas diabetes was only predictive of all-cause mortality. Smoking habit and atrial fibrillation had no prognostic value. Similar parameters were also predictive of short-term mortality, but not identical. CONCLUSIONS: Our study has shown that in high-risk patients post MI, who have been preselected using LVEF or frequent ventricular premature beats, demographic and clinical features are powerful predictors of mortality in the thrombolytic era. We propose that demographic and clinical factors should be considered when designing risk stratification or survival studies, or when identifying high-risk patients for prophylactic implantable cardiodefibrillator therapy.

Temporal trends on the risk of arrhythmic vs. non-arrhythmic deaths in high-risk patients after myocardial infarction: a combined analysis from multicentre trials.

AIMS: An understanding of the temporal trends on the risks of arrhythmic death (AD) vs. non-arrhythmic deaths (NAD) after myocardial infarction (MI) is crucial in deciding the optimal timing for risk stratification and treatment window for prophylactic antiarrhythmic treatment. However, contemporary data on such information is lacking. METHODS AND RESULTS: Individual patient data were pooled from the placebo arms of EMIAT, CAMIAT, SWORD, TRACE, and DIAMOND-MI who had a recent MI and left ventricular ejection fraction (LVEF) <40% or frequent ventricular premature beats (VPBs). Temporal trends were investigated for all studies from day 45 after acute myocardial infarction (AMI) to account for different recruitment periods between trials, and then from the onset of MI for TRACE and DIAMOND-MI that recruited patients within 2 weeks after MI. In total, 3104 patients (median age 65, range: 23-92; 2471 males) were pooled from all five studies, with a total of 487 deaths at 2-year follow-up; 220 deaths were ADs and 172 were NADs. The risks of both AD and NAD were highest in the first 6 months but the risk of AD was consistently higher than that of NAD throughout the 2-year period [rate of death/100 person-year at risk (AD/NAD): 8.09/6.07 (45 days to 6 months), 4.07/3.35 (>6-12 months), 4.34/3.60 (>12-18 months), 3.76/2.77 (>18-24 months)]. There were significant interactions between the temporal trends of mortalities and gender (P=0.03) and history of hypertension (P=0.04). A similar trend was observed when mortality was measured from time of onset of MI from the combined TRACE and DIAMOND-MI dataset. CONCLUSION: Our study provided the first contemporary evidence that in high-risk post-MI patients with LVEF <40% or frequent VPBs, the risk of AD was higher than that of NAD for up to 2 years although in female patients, they became increasingly more likely to die from NAD after 6 months. Therefore, risk stratification of post-MI patient at high risk of AD remains a worthwhile exercise. However, the risks of AD (and NAD) were highest in the first 6 months after AMI and level-off thereafter, suggesting that the optimal window period for risk stratification for implantable cardioverter defibrillator after AMI is in the first 6 months.

Potential cardiac toxicity of H1-antihistamines.

Nonsedating H1-antihistamines are widely prescribed for the treatment of allergic disorders because of their lack of sedative and anticholinergic effects; however, certain nonsedating antihistamines such as terfenadine and astemizole are now known to cause QT prolongation and TdP, particularly in overdosage or with concomitant ingestion of imidazole antifungals or macrolide antibiotics. Mechanistic studies showed that the cardiotoxic effects of some nonsedating antihistamines are due to the inhibition of repolarization potassium channels, particularly IKr, which leads to prolongation of the action potential and QT interval, and the development of early after-depolarization, which triggers TdP. Patients at risk of developing TdP, such as those with congenital long QT syndrome, cardiac disease, liver disease, electrolyte disturbance, or those taking drugs that can prolong QT interval, should avoid nonsedating antihistamines that are also capable of prolonging the QT interval. Many questions still need to be answered, such as the role of other potassium channels (IKs, ITo, and Iped) and the relative expression of various potassium channels in different individuals, which may be important in the pathogenesis of TdP with nonsedating antihistamines. There is also a lack of information on the cardiac actions of newer nonsedating antihistamines. The evidence so far indicates that the potential to cause ventricular arrhythmias is not a class effect and that loratadine, cetirizine, and fexofenadine are not associated with QT prolongation, TdP, or other ventricular arrhythmias. It is hoped that with a better understanding of the arrhythmogenic mechanism of nonsedating antihistamines, we will be able to identify patients at risk and prevent any cardiac toxicity associated with H1-antihistamines, and ultimately, death.