Evaluation of Differences in Automated QT/QTc Measurements between Fukuda Denshi and Nihon Koden Systems

Background

Automatic measurement becomes a preference, and indeed a necessity, when analyzing 1000 s of ECGs in the setting of either drug-inducing QT prolongation screening or genome-wide association studies of QT interval. The problem is that individual manufacturers apply different computerized algorithms to measure QT interval. We conducted a comparative study to assess the outcomes with different automated measurements of QT interval between ECG machine manufacturers and validated the related heart rate correction methods.

Methods and Results

Herein, we directly compared these different commercial systems using 10,529 Fukuda Denshi ECGs and 72,754 Nihon Kohden ECGs taken in healthy Japanese volunteers. Log-transformed data revealed an equal optimal heart rate correction formula of QT interval for Fukuda Denshi and Nihon Kohden, in the form of QTc = QT/RR^−0.347. However, with the raw data, the optimal heart rate correction formula of QT interval was in the form of QTc = QT+0.156×(1-RR) for Fukuda Denshi and QTc = QT+0.152×(1-RR) for Nihon Kohden. After optimization of heart rate correction of QT interval by the linear regression model using either log-transformed data or raw data, QTc interval was ∼10 ms longer in Nihon Kohden ECGs than in those recorded on Fukuda Denshi machines. Indeed, regression analysis revealed that differences in the ECG machine used had up to a two-fold larger impact on QT variation than gender difference. Such an impact is likely to be of considerable importance when ECGs for a given individual are recorded on different machines in the setting of multi-institutional joint research.

Conclusions

We recommend that ECG machines of the same manufacturer should be used to measure QT and RR intervals in the setting of multi-institutional joint research. It is desirable to unify the computer algorithm for automatic QT and RR measurements from an ECG.     

Repolarization Parameters Are Associated With Mortality In Chagas Disease Patients In The United States

Objective

The goal of this study was to examine the association between ECG repolarization parameters and mortality in Chagas disease (CD) patients living in the United States.

Methods

CD patients with cardiomyopathy (CM) and bundle branch block (BBB) or BBB alone were compared to age- and sex-matched controls. QT interval, QT dispersion (QTd), T wave peak to T wave end duration (Tp-Te) and T wave peak to T wave end dispersion ((Tp-Te)d) were measured. Presence of fractionated QRS (fQRS) was also assessed. The main outcome measure was the association between ECG parameters and mortality or need for cardiac transplant.

Results

A total of 18 CM and 13 BBB CD patients were studied with 97% originating from Mexico or Central America. QTd (60.0±15.0 ms vs 43.5±9.8 ms, P=0.0002), Tp-Te (102.6±29.3 ms vs 77.1±11.0 ms, P=0.0002) and (Tp-Te)d (39.5±9.4 ms vs 22.7±7.6 ms, P<0.0001) were prolonged in CD CM patients compared to CM controls. Chagas CM patients had more fQRS then controls (84.2±0.10% vs 33.3±0.11%, p=0.0005). QTd (59.9±15.0 ms vs 29.5±6.9 ms, P=0.0001) and (Tp-Te)d (40.0±15.9 ms vs 18.5±5.4 ms, p<0.0001) were longer in the CD BBB group compared to BBB controls. Univariate analysis showed QTd (56.9±15.0 ms vs 46.5±17.3 ms, p=0.0412) and (Tp-Te)d (36.8±13.5 ms vs 28.5±13.3 ms, p=0.0395) were associated with death and/or need for cardiac transplant.

Conclusion

Our results indicate that P-max and PD are useful electrocardiographic markers for identifying the β-TM-high-risk patients for AF onset, even when the cardiac function is conserved.     

Conventional QT Variability Measurement vs. Template Matching Techniques: Comparison of Performance Using Simulated and Real ECG

Increased beat-to-beat variability in the QT interval (QTV) of ECG has been associated with increased risk for sudden cardiac death, but its measurement is technically challenging and currently not standardized. The aim of this study was to investigate the performance of commonly used beat-to-beat QT interval measurement algorithms. Three different methods (conventional, template stretching and template time shifting) were subjected to simulated data featuring typical ECG recording issues (broadband noise, baseline wander, amplitude modulation) and real short-term ECG of patients before and after infusion of sotalol, a QT interval prolonging drug. Among the three algorithms, the conventional algorithm was most susceptible to noise whereas the template time shifting algorithm showed superior overall performance on simulated and real ECG. None of the algorithms was able to detect increased beat-to-beat QT interval variability after sotalol infusion despite marked prolongation of the average QT interval. The QTV estimates of all three algorithms were inversely correlated with the amplitude of the T wave. In conclusion, template matching algorithms, in particular the time shifting algorithm, are recommended for beat-to-beat variability measurement of QT interval in body surface ECG. Recording noise, T wave amplitude and the beat-rejection strategy are important factors of QTV measurement and require further investigation.     

The Application of Root Mean Square Electrocardiography (RMS ECG) for the Detection of Acquired and Congenital Long QT Syndrome

Background

Precise measurement of the QT interval is often hampered by difficulty determining the end of the low amplitude T wave. Root mean square electrocardiography (RMS ECG) provides a novel alternative measure of ventricular repolarization. Experimental data have shown that the interval between the RMS ECG QRS and T wave peaks (RT_PK) closely reflects the mean ventricular action potential duration while the RMS T wave width (TW) tracks the dispersion of repolarization timing. Here, we tested the precision of RMS ECG to assess ventricular repolarization in humans in the setting of drug-induced and congenital Long QT Syndrome (LQTS).

Methods

RMS ECG signals were derived from high-resolution 24 hour Holter monitor recordings from 68 subjects after receiving placebo and moxifloxacin and from standard 12 lead ECGs obtained in 97 subjects with LQTS and 97 age- and sex-matched controls. RT_PK, QT_RMS and RMS TW intervals were automatically measured using custom software and compared to traditional QT measures using lead II.

Results

All measures of repolarization were prolonged during moxifloxacin administration and in LQTS subjects, but the variance of RMS intervals was significantly smaller than traditional lead II measurements. TW was prolonged during moxifloxacin and in subjects with LQT-2, but not LQT-1 or LQT-3.

Conclusion

These data validate the application of RMS ECG for the detection of drug-induced and congenital LQTS. RMS ECG measurements are more precise than the current standard of care lead II measurements.     

Coffee, alcohol, smoking, physical activity and QT interval duration: results from the Third National Health and Nutrition Examination Survey

Background

Abnormalities in the electrocardiographic QT interval duration have been associated with an increased risk of ventricular arrhythmias and sudden cardiac death. However, there is substantial uncertainty about the effect of modifiable factors such as coffee intake, cigarette smoking, alcohol consumption, and physical activity on QT interval duration.

Methods

We studied 7795 men and women from the Third National Health and Nutrition Survey (NHANES III, 1988–1994). Baseline QT interval was measured from the standard 12-lead electrocardiogram. Coffee and tea intake, alcohol consumption, leisure-time physical activities over the past month, and lifetime smoking habits were determined using validated questionnaires during the home interview.

Results

In the fully adjusted model, the average differences in QT interval comparing participants drinking ≥6 cups/day to those who did not drink any were −1.2 ms (95% CI −4.4 to 2.0) for coffee, and −2.0 ms (−11.2 to 7.3) for tea, respectively. The average differences in QT interval duration comparing current to never smokers was 1.2 ms (−0.6 to 2.9) while the average difference in QT interval duration comparing participants drinking ≥7 drinks/week to non-drinkers was 1.8 ms (−0.5 to 4.0). The age, race/ethnicity, and RR-interval adjusted differences in average QT interval duration comparing men with binge drinking episodes to non-drinkers or drinkers without binge drinking were 2.8 ms (0.4 to 5.3) and 4.0 ms (1.6 to 6.4), respectively. The corresponding differences in women were 1.1 (−2.9 to 5.2) and 1.7 ms (−2.3 to 5.7). Finally, the average differences in QT interval comparing the highest vs. the lowest categories of total physical activity was −0.8 ms (−3.0 to 1.4).

Conclusion

Binge drinking was associated with longer QT interval in men but not in women. QT interval duration was not associated with other modifiable factors including coffee and tea intake, smoking, and physical activity.     

A Gender-Based Analysis of High School Athletes Using Computerized Electrocardiogram Measurements

Background

The addition of the ECG to the preparticipation examination (PPE) of high school athletes has been a topic for debate. Defining the difference between the high school male and female ECG is crucial to help initiate its implementation in the High School PPE. Establishing the different parameters set for the male and female ECG would help to reduce false positives. We examined the effect of gender on the high school athlete ECG by obtaining and analyzing ECG measurements of high school athletes from Henry M. Gunn High School.

Methods

In 2011 and 2012, computerized Electrocardiograms were recorded and analyzed on 181 athletes (52.5% male; mean age 16.1±1.1 years) who participated in 17 different sports. ECG statistics included intervals and durations in all 3 axes (X, Y, Z) to calculate 12 lead voltage sums, QRS Amplitude, QT interval, QRS Duration, and the sum of the R wave in V5 and the S Wave in V2 (RS Sum).

Results

By computer analysis, we demonstrated that male athletes had significantly greater QRS duration, Q-wave duration, and T wave amplitude. (P<0.05). By contrast, female athletes had a significantly greater QTc interval. (P<0.05).

Conclusion

The differences in ECG measurements in high school athletes are strongly associated with gender. However, body size does not correlate with the aforementioned ECG measurements. Our tables of the gender-specific parameters can help facilitate the development of a more large scale and in-depth ECG analysis for screening high school athletes in the future.     

Assessment of pulse rate variability by the method of pulse frequency demodulation

Background  

Due to its easy applicability, pulse wave has been proposed as a surrogate of electrocardiogram (ECG) for the analysis of heart rate variability (HRV). However, its smoother waveform precludes accurate measurement of pulse-to-pulse interval by fiducial-point algorithms. Here we report a pulse frequency demodulation (PFDM) technique as a method for extracting instantaneous pulse rate function directly from pulse wave signal and its usefulness for assessing pulse rate variability (PRV).     

Differential changes in QTc duration during in-hospital haloperidol use

Aims

To evaluate changes in QT duration during low-dose haloperidol use, and determine associations between clinical variables and potentially dangerous QT prolongation.

Methods

In a retrospective cohort study in a tertiary university teaching hospital in The Netherlands, all 1788 patients receiving haloperidol between 2005 and 2007 were studied; ninety-seven were suitable for final analysis. Rate-corrected QT duration (QTc) was measured before, during and after haloperidol use. Clinical variables before haloperidol use and at the time of each ECG recording were retrieved from hospital charts. Mixed model analysis was used to estimate changes in QT duration. Risk factors for potentially dangerous QT prolongation were estimated by logistic regression analysis.

Results

Patients with normal before-haloperidol QTc duration (male ≤430 ms, female ≤450 ms) had a significant increase in QTc duration of 23 ms during haloperidol use; twenty-three percent of patients rose to abnormal levels (male ≥450 ms, female ≥470 ms). In contrast, a significant decrease occurred in patients with borderline (male 430–450 ms, female 450–470 ms) or abnormal before-haloperidol QTc duration (15 ms and 46 ms, respectively); twenty-three percent of patients in the borderline group, and only 9% of patients in the abnormal group obtained abnormal levels. Potentially dangerous QTc prolongation was independently associated with surgery before haloperidol use (OR_adj 34.9, p = 0.009) and before-haloperidol QTc duration (OR_adj 0.94, p = 0.004).

Conclusion

QTc duration during haloperidol use changes differentially, increasing in patients with normal before-haloperidol QTc duration, but decreasing in patients with prolonged before-haloperidol QTc duration. Shorter before-haloperidol QTc duration and surgery before haloperidol use predict potentially dangerous QTc prolongation.     

QT interval measurement using RMED curve; a novel approach based on wavelet techniques

Hypothesis/objective: Prolonged QT interval is an index of propensity for dangerous ventricular tachyarrhythmias. The aim of this article is to establish an automatic algorithm for QT interval measurement.

Method: The proposed method is based on the continuous wavelet transform. In this method, the concepts of the rescaled wavelet coefficients and dominant scales of the electrocardiogram (ECG) components are used to perform detection of ECG characteristic points. A new concept of rescaled maximum energy density is introduced so as to perform the estimation of the QT interval.

Results and conclusion: We have applied the algorithm to the PTB database of the Physiobank?Physionet in lead II. Then, the results were evaluated using pertinent reference QT. The criterion used for evaluation of the method's performance is the root mean square (RMS) error. The method approached the RMS error of 27.89 ms for 549 subjects. The proposed method is fast, simple and is applicable to a wide range of ECG cardio cycle morphologies.     

Subject-specific profiles of QT/RR hysteresis

The time lag of the QT interval adaptation to heart rate changes (QT/RR hysteresis) was studied in 40 healthy subjects (18 females; mean age, 30.4+/-8.1 yr) with 3 separate daytime (>13 h) 12-lead electrocardiograms (ECG) in each subject. In each recording, 330 individual 10-s ECG segments were measured, including 100 segments preceded by 2 min of heart rate varying greater than +/-2 beats/min. Other segments were preceded by a stable heart rate. In segments preceded by variable rate, QT/RR hysteresis was characterized by lambda parameters of the exponential decay models. The intrasubject SDs of lambda values were compared with the intersubject SD of the individual means. The lambda values were also correlated to individually optimized parameters of heart rate correction. Intrasubject SDs of lambda were substantially smaller than the population SD of individual means (0.390+/-0.197 vs. 0.711, P<0.0001). The lambda values were unrelated to the QT/RR correction parameters. When compared with the corrected QT (QTc) for averaged RR intervals in 10-s ECGs and with the averaged RR intervals in 2-min history, QTc for QT/RR hysteresis led to a substantially smaller SD of QTc values (11.4+/-2.00, 6.33+/-1.31, and 4.66+/-0.85 ms, respectively, P<0.0001). Thus the speed with which the QT interval adapts to heart rate changes is highly individual with intrasubject stability and intersubject variability. QT/RR hysteresis is independent of the static QT/RR relationship and should be considered as a separate physiological process. The combination of individual heart rate correction with individual hysteresis correction of the QT interval is likely to lead to substantial improvements of cardiac repolarization studies.     

Thyroid Hormones and Electrocardiographic Parameters: Findings from the Third National Health and Nutrition Examination Survey

Introduction

Altered thyroid status exerts a major effect on the heart. Individuals with hypo- or hyperthyroidism showed various changes in electrocardiograms. However, little is known about how variations in thyroid hormone levels within the normal range affect electrical activities of the heart in the general population.

Methods and Results

We conducted a cross-sectional analysis of 5,990 men and women from the Third National Health and Nutrition Examination Survey. Serum total T4 was measured by immunoassay and TSH was measured by chemiluminescent assay. We categorized T4 and TSH into 7 groups with cut-offs at the 5^th, 20^th, 40^th, 60^th, 80^th, and 95^th percentiles of the weighted population distribution. Electrocardiographic parameters were measured from the standard 12-lead electrocardiogram. We found a positive linear association between serum total T4 level and heart rate in men, and a U-shape association between T4 and PR interval in men and women. TSH level was positively associated with QRS interval in men, while a U-shape association between TSH and QRS was observed in women. No clear graded association between thyroid hormones and corrected QT or JT was found, except that men in the highest category of T4 levels appeared to have longer corrected QT and JT, and men in the lowest category of T4 appeared to have shorter corrected QT and JT.

Conclusions

Variation in thyroid hormone levels in the general population, even within the normal range, was associated with various ECG changes.     

Early repolarization with horizontal ST segment may be associated with aborted sudden cardiac arrest: a retrospective case control study

Background

Patients with systemic lupus erythematosus (SLE) have increased cardiovascular morbidity and mortality. Although autopsy studies have documented that the heart is affected in most SLE patients, clinical manifestations occur in less than 10%. QT dispersion is a new parameter that can be used to assess homogeneity of cardiac repolarization and autonomic function. We compared the increase in QT dispersion in SLE patients with high disease activity and mild or moderate disease activity.

Methods and Results

One hundred twenty-four patients with SLE were enrolled in the study. Complete history and physical exam, ECG, echocardiography, exercise test and SLE disease activity index (SLEDAI) were recorded. Twenty patients were excluded on the basis of our exclusion criteria. The patients were divided to two groups based on SLEDAI: 54 in the high-score group (SLEDAI > 10) and 50 in the low-score group (SLEDAI < 10). QT dispersion was significantly higher in high-score group (58.31 ± 18.66 vs. 47.90 ± 17.41 respectively; P < 0.004). QT dispersion was not significantly higher in patients who had received hydroxychloroquine (54.17 ± 19.36 vs. 50.82 ± 15.96, P = 0.45) or corticosteroids (53.58 ± 19.16 vs. 50.40 + 11.59, P = 0.47). There was a statistically significant correlation between abnormal echocardiographic findings (abnormalities of pericardial effusion, pericarditis, pulmonary hypertension and Libman-Sacks endocarditis) and SLEADI (P < 0.004).

Conclusions

QT dispersion can be a useful, simple noninvasive method for the early detection of cardiac involvement in SLE patients with active disease. Concerning high chance of cardiac involvement, cardiovascular evaluation for every SLE patient with a SLEDAI higher than 10 may be recommended.

Trial registration

Clinicaltrial.gov registration NCT01031797     

Morphometric and morphologic parameters of the heart in healthy Alouatta guariba clamitans (Cabrera, 1940)

Background

This study aimed at assessing the heart function of one neotropical primate (Alouatta guariba clamitans) kept in captivity using radiography, electrocardiogram (ECG) and Doppler echocardiography.

Methods

Ten adult healthy howler monkeys (A. g. clamitans) were evaluated under general anaesthesia. Vertebral Heart Scores (VHS) were obtained from radiographic studies. Ejection fraction, shortening fraction of left ventricle, left atrial/aortic root ratio, ascending aortic diameter, peak velocity of pulmonary, mitral, tricuspid and aortic blood flow and other values were measured by Doppler echocardiography. Heart rate, mean electrical axis of QRS complex, P, Q, R, S, T amplitude, P, PR interval, QRS, QT interval duration and ST segment unbalancing were measured by ECG.

Results and conclusions

Exam techniques were akin the ones used in humans. Doppler echocardiographic, radiographic, electrocardiographic and clinical parameters for howler monkey were described and correlated. The results have shown profiles of cardiovascular function and structure of A. g. clamitans.     

Overlapping LQT1 and LQT2 phenotype in a patient with long QT syndrome associated with loss-of-function variations in KCNQ1 and KCNH2

Long QT syndrome (LQTS) is an inherited disorder characterized by prolonged QT intervals and potentially life-threatening arrhythmias. Mutations in 12 different genes have been associated with LQTS. Here we describe a patient with LQTS who has a mutation in KCNQ1 as well as a polymorphism in KCNH2. The proband (MMRL0362), a 32-year-old female, exhibited multiple ventricular extrasystoles and one syncope. Her ECG (QT interval corrected for heart rate (QTc) = 518ms) showed an LQT2 morphology in leads V4-V6 and LQT1 morphology in leads V1-V2. Genomic DNA was isolated from lymphocytes. All exons and intron borders of 7 LQTS susceptibility genes were amplified and sequenced. Variations were detected predicting a novel missense mutation (V110I) in KCNQ1, as well as a common polymorphism in KCNH2 (K897T). We expressed wild-type (WT) or V110I Kv7.1 channels in CHO-K1 cells cotransfected with KCNE1 and performed patch-clamp analysis. In addition, WT or K897T Kv11.1 were also studied by patch clamp. Current-voltage (I-V) relations for V110I showed a significant reduction in both developing and tail current densities compared with WT at potentials >+20 mV (p < 0.05; n = 8 cells, each group), suggesting a reduction in IKs currents. K897T- Kv11.1 channels displayed a significantly reduced tail current density compared with WT-Kv11.1 at potentials >+10 mV. Interestingly, channel availability assessed using a triple-pulse protocol was slightly greater for K897T compared with WT (V0.5 = -53.1 ± 1.13 mV and -60.7 ± 1.15 mV for K897T and WT, respectively; p < 0.05). Comparison of the fully activated I-V revealed no difference in the rectification properties between WT and K897T channels. We report a patient with a loss-of-function mutation in KCNQ1 and a loss-of-function polymorphism in KCNH2. Our results suggest that a reduction of both IKr and IKs underlies the combined LQT1 and LQT2 phenotype observed in this patient.     

Advanced Age, Female Gender and Delay in Pacemaker Implantation May Cause TdP in Patients With Complete Atrioventricular Block

Aim

We aimed to report the clinical features related to torsades de pointes (TdP) in patients with complete AV block (CAVB).

Methods

Patients with CAVB who were admitted to our instituition between January 2007 and January 2010 were retrospectively evaluated in terms of the occurence of TdP. The clinical features were compared in patients with and without TdP using the software of SPSS.

Results

Sixty-four patients were determined to have CAVB. Three of them had documented episodes of TdP. All three patients experiencing TdP were females, whereas 48% of the patients with CAVB were females. The mean age of patients with TdP was significantly greater than the mean age of the other patients (85 ±3 vs. 78±7.6, respectively; p<0.05). In our archives, bradycardia exposure time could be determined in only 49 patients without TdP. Among them, just 10 patients had been exposed to bradycardia over 48 hours, whereas all of the 3 patients with TdP had been exposed to bradycardia over 48 hours (p<0.05). Additionally, in two patients with TdP, we demonstrated that QT and QTc prolongation increases as the duration of bradycardia is extended. Furthermore, all patients with TdP had notched T waves in the ECG on the occurrence day of TdP, whereas they did not have any notched T wave in their ECG on the admission day.

Conclusion

Among the patients with CAVB, elderly females are more susceptible to development of TdP. Delay in institution of physiological heart rate leads to further QT prolongation and thereby to TdP. Besides QT prolongation, the finding of T wave notching on ECG may also have a predictive value for TdP.     

Evaluation of B-type Natriuretic Peptide for validation of a heart failure register in primary care

Background

Studies suggest that Goal Directed Therapy (GDT) results in improved outcome following major surgery. However, there is concern that pre-emptive use of inotropic therapy may lead to an increased incidence of myocardial ischaemia and infarction.

Methods

Post hoc analysis of data collected prospectively during a randomised controlled trial of the effects of post-operative GDT in high-risk general surgical patients. Serum troponin T concentrations were measured at baseline and on day 1 and day 2 following surgery. Continuous ECG monitoring was performed during the eight hour intervention period. Patients were followed up for predefined cardiac complications. A univariate analysis was performed to identify any associations between potential risk factors for myocardial injury and elevated troponin T concentrations.

Results

GDT was associated with fewer complications, and a reduced duration of hospital stay. Troponin T concentrations above 0.01 μg l^-1 were identified in eight patients in the GDT group and six in the control group. Values increased above 0.05 μg l^-1 in four patients in the GDT group and two patients in the control group. There were no overall differences in the incidence of elevated troponin T concentrations. The incidence of cardiovascular complications was also similar. None of the patients, in whom troponin T concentrations were elevated, developed ECG changes indicating myocardial ischaemia during the intervention period. The only factor to be associated with elevated troponin T concentrations following surgery was end-stage renal failure.

Conclusion

The use of post-operative GDT does not result in an increased incidence of myocardial injury.     

Fenoldopam use in a burn intensive care unit: a retrospective study

Background

We sought to evaluate agreement between a new and widely implemented method of temperature measurement in critical care, temporal artery thermometry and an established method of core temperature measurement, bladder thermometry as performed in clinical practice.

Methods

Temperatures were simultaneously recorded hourly (n = 736 observations) using both devices as part of routine clinical monitoring in 14 critically ill adult patients with temperatures ranging ≥1°C prior to consent.

Results

The mean difference between temporal artery and bladder temperatures measured was -0.44°C (95% confidence interval, -0.47°C to -0.41°C), with temporal artery readings lower than bladder temperatures. Agreement between the two devices was greatest for normothermia (36.0°C to < 38.3°C) (mean difference -0.35°C [95% confidence interval, -0.37°C to -0.33°C]). The temporal artery thermometer recorded higher temperatures during hypothermia (< 36°C) (mean difference 0.66°C [95% confidence interval, 0.53°C to 0.79°C]) and lower temperatures during hyperthermia (≥38.3°C) (mean difference -0.90°C [95% confidence interval, -0.99°C to -0.81°C]). The sensitivity for detecting fever (core temperature ≥38.3°C) using the temporal artery thermometer was 0.26 (95% confidence interval, 0.20 to 0.33), and the specificity was 0.99 (95% confidence interval, 0.98 to 0.99). The positive likelihood ratio for fever was 24.6 (95% confidence interval, 10.7 to 56.8); the negative likelihood ratio was 0.75 (95% confidence interval, 0.68 to 0.82).

Conclusions

Temporal artery thermometry produces somewhat surprising disagreement with an established method of core temperature measurement and should not to be used in situations where body temperature needs to be measured with accuracy.     

GRACE and TIMI risk scores but not stress imaging predict long-term cardiovascular follow-up in patients with chest pain after a rule-out protocol

Objective

To determine the long-term prognostic value of stress imaging and clinical risk scoring for cardiovascular mortality in chest pain patients after ruling out acute coronary syndrome (ACS).

Methods

A standard rule-out protocol was performed in emergency room patients with a normal or non-diagnostic admission electrocardiogram (ECG) within 6 h of chest pain onset. ACS patients were identified by troponin T, recurrent angina and serial ECG. Dobutamine stress echocardiography (DSE) was performed after ACS was ruled out. Myocardial perfusion scintigraphy (MPS) was performed within 6 months in an outpatient setting according to the physician’s discretion.

Results

524 patients were included. GRACE and TIMI risk scores were 75 (57–96) and 1 (0–2) in the rule-out ACS group, and 89 (74–107) and 2 (1–3) in the ACS group, respectively (median, interquartile range). Follow-up (median 9.4 (8.9–10.0) years) was complete in 96%. 350 of 379 rule-out ACS patients had an interpretable DSE and 52 patients underwent an MPS. 21 of the rule-out ACS patients (6%) died of a cardiovascular cause compared with 24 (17%) ACS patients (p?<?0.001). For rule-out ACS patients, C-statistics were 0.829 and 0.803 for the GRACE and TIMI scores. In these patients, DSE and MPS outcome did not predict long-term cardiovascular mortality. In multivariate analysis, known chronic heart failure, ACE inhibitor use, and GRACE score were independent predictors of cardiovascular mortality.

Conclusions

TIMI and GRACE score but not DSE and MPS are accurate predictors of long-term cardiovascular mortality, even in chest pain patients with a normal or non-diagnostic electrocardiogram undergoing a rule-out protocol.     

Rate-correction technique for QT interval in long-term telemetry ECG recording in beagle dogs.

The establishment of a new rate-correction method for the QT interval is presented for long-term telemetry ECG recording in free-moving beagle dogs. First, in order to define the QT-RR relation to derive the correction formula, the diurnal variations of the QT and RR intervals and the influencing factors were analyzed, and the QT-RR regression coefficient beta was estimated under various conditions: steady and non-steady states of animal, light and dark periods, and over 24 h. In the results, the diurnal rhythm of the QT interval was synchronized with the RR interval reflecting the physical and emotional states of the animal. The coefficient beta had considerable variation during the day: beta; 0.276 +/- 0.052 (maximum to minimum: 0.495 to 0.153). Thus, it was considered that the ideal rate-correction technique for telemetry ECG requires the selection of a flexible coefficient beta adjusted to the condition of the measurement. Therefore, rate-correction utilizing analysis of covariance estimating the coefficient beta for each dog, was compared with previously proposed formulas which fix the rate-correction coefficient, based on the capacity to dissociate the effects of heart rate on the QT interval. This was then tested by the levels of discrimination apparent in the QT prolongation caused by a class III antiarrhythmic drug, which ranked the formulas on the levels of correction achieved as follows: covariance adjustment > Matsunaga > Van de Water > Bazett. Thus, the rate-correction method utilizing analysis of covariance is proven adequate for data from telemetry ECG recordings.     

In vivo recording of adult zebrafish electrocardiogram and assessment of drug-induced QT prolongation

In the last decade the zebrafish has become a major model organism for the study of development and organogenesis. To maximize the experimental utility of this organism, it will be important to establish methods for adult phenotyping. We previously proposed that the embryonic zebrafish may be useful in high-throughput screening for drug-induced cardiotoxicity. We now describe a method for the reproducible recording of the adult zebrafish ECG and illustrate its application in the investigation of QT-prolonging drugs. Zebrafish ECGs were obtained by inserting two needle electrodes through the ventral epidermis. Fish were perfused orally, and motion artifacts were eliminated with a paralytic dose of mu-conotoxin GIIIB. Test compounds were delivered via the perfusion system. Without a means of hydration and oxygenation, the fish succumb rapidly. The use of a perfusion system allowed stable recording for > 6 h. Baseline conduction intervals were as follows: PR, 66 ms (SD 14); QRS, 34 ms (SD 11); QT, 242 ms (SD 54); and R-R, 398 ms (SD 77). The known QT-prolonging agents astemizole, haloperidol, pimozide, and terfenadine caused corrected QT increases of 18% (SD 9), 16% (SD 11), 17% (SD 9), and 11% (SD 6), respectively. The control drugs clonidine, penicillin and propranolol did not prolong the corrected QT interval. In conclusion, perfusion and muscular paralysis allows stable, low-noise recording of zebrafish ECGs. Agents known to cause QT prolongation in humans caused QT prolongation in fish in each case. The development of rigorous tools for the phenotyping of adult zebrafish will complement the high-throughput assays currently under development for embryonic and larval fish.