Clinical and molecular genetic risk determinants in adult long QT syndrome type 1 and 2 patients : Koponen et al. Follow-up of adult LQTS patients.

BACKGROUND: Long QT syndrome (LQTS) is an inherited cardiac disorder predisposing to sudden cardiac death (SCD). We studied factors affecting the clinical course of genetically confirmed patients, in particular those not receiving ß-blocker treatment. In addition, an attempt was made to associate risk of events to specific types of KCNQ1 and KCNH2 mutations. METHODS: A follow-up study covering a mean of 18.6 ± 6.1 years was conducted in 867 genetically confirmed LQT1 and LQT2 patients and 654 non-carrier relatives aged 18-40 years. Cox regression models were used to evaluate the contribution of clinical and genetic risk factors to cardiac events. RESULTS: In mutation carriers, risk factors for cardiac events before initiation of ß-blocker included LQT2 genotype (hazard ratio [HR] = 2.1, p = 0.002), female gender (HR = 3.2, p < 0.001), a cardiac event before the age of 18 years (HR = 5.9, p < 0.001), and QTc ≥500 ms (vs < 470 ms, HR = 2.7, p = 0.001). LQT1 patients carrying the KCNQ1 D317N mutation were at higher risk (HR = 3.0-3.9, p < 0.001-0.03) compared to G589D, c.1129-2A > G and other KCNQ1 mutation carriers after adjusting for gender, QTc duration, and cardiac events before age 18. KCNH2 c.453delC, L552S and R176W mutations associated with lower risk (HR = 0.11-0.23, p < 0.001) than other KCNH2 mutations. CONCLUSIONS: LQT2 (compared to LQT1), female gender, a cardiac event before age 18, and long QT interval increased the risk of cardiac events in LQTS patients aged 18 to 40 years. The nature of the underlying mutation may be associated with risk variation in both LQT1 and LQT2. The identification of high-risk and low-risk mutations may enhance risk stratification.

Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural myocardial infarction - a prospective CMR study.

BACKGROUND: Large myocardial infarction (MI) is associated with adverse left ventricular (LV) remodeling (LVR). We studied the nature of LVR, with specific attention to non-transmural MIs, and the association of peak CK-MB with recovery and chronic phase scar size and LVR. METHODS: Altogether 41 patients underwent prospectively repeated cardiovascular magnetic resonance at a median of 22 (interquartile range 9-29) days and 10 (8-16) months after the first revascularized MI. Transmural MI was defined as ≥75% enhancement in at least one myocardial segment. RESULTS: Peak CK-MB was 86 (40-216) µg/L in median, while recovery and chronic phase scar size were 13 (3-23) % and 8 (2-19) %. Altogether 33 patients (81%) had a non-transmural MI. Peak CK-MB had a strong correlation with recovery and chronic scar size (r ≥ 0.80 for all, r ≥ 0.74 for non-transmural MIs; p < 0.001). Peak CK-MB, recovery scar size, and chronic scar size, were all strongly correlated with chronic wall motion abnormality index (WMAi) (r ≥ 0.75 for all, r ≥ 0.73 for non-transmural MIs; p < 0.001). There was proportional scar size and LV mass resorption of 26% (0-50%) and 6% (- 2-14%) in median. Young age (< 60 years, median) was associated with greater LV mass resorption (median 9%vs.1%, p = 0.007). CONCLUSIONS: Peak CK-MB has a strong association with chronic scar size and wall motion abnormalities after revascularized non-transmural MI. Considerable infarct resorption happens after the first-month recovery phase. LV mass resorption is related to age, being more common in younger patients.

Slowed depolarization and irregular repolarization in catecholaminergic polymorphic ventricular tachycardia: a study from cellular Ca2+ transients and action potentials to clinical monophasic action potentials and electrocardiography.

AIMS: Spontaneous Ca2+ release leads to afterdepolarizations and triggered arrhythmia in catecholaminergic polymorphic ventricular tachycardia (CPVT). Irregular Ca2+ release is hypothesized to manifest as slowed depolarization and irregular repolarization. Our goal was to study depolarization and repolarization abnormalities in CPVT, as they remain largely uninvestigated. METHODS AND RESULTS: We studied intracellular Ca2+ handling and action potentials (APs) in an induced pluripotent stem cell (iPSC) model of CPVT. Induced pluripotent stem cell cardiomyocytes from a RyR2-P2328S patient showed increased non-alternating variability of Ca2+ transients in response to isoproterenol. ß-Agonists decreased AP upslope velocity in CPVT cells and in monophasic AP recordings of CPVT patients. We compared 24 h electrocardiograms (ECGs) of 19 CPVT patients carrying RyR2 mutations and 19 healthy controls. Short-term variability (STV) of the QT interval was 6.9 ± 0.5 ms in CPVT patients vs. 5.5 ± 0.4 ms in controls (P < 0.05) and associated with a history of arrhythmic events. Mean T-wave alternans (TWA) was 25 ± 1.4 µV in CPVT patients vs. 31 ± 2.0 µV in controls (P < 0.05). Older CPVT patients showed lower maximal upslope velocity of the ECG R-spike than control patients. CONCLUSION: Catecholaminergic polymorphic ventricular tachycardia patients show higher STV of repolarization but lower TWA on the 24 h ECG than control patients, which is likely to reflect increased non-alternating variability of Ca2+ release by mutant RyR2s as observed in vitro. ß-Agonists slow depolarization in RyR2-mutant cells and in CPVT patients. These findings may constitute a marker of arrhythmogenicity.

Antiarrhythmic Action of Flecainide in Polymorphic Ventricular Arrhythmias Caused by a Gain-of-Function Mutation in the Nav 1.5 Sodium Channel.

BACKGROUND: The cardiac sodium channel Nav 1.5, encoded by the gene SCN5A, is associated with a wide spectrum of hereditary arrhythmias. The gain-of-function mutation p.I141V in SCN5A was identified in a large multigenerational family with exercise-induced polymorphic ventricular arrhythmias. The purpose of this study was to evaluate the molecular and clinical effects of flecainide administration on patients with this syndrome. METHODS: Eleven p.I141V carriers who exhibited frequent multiformic premature ventricular complexes (PVCs) during exercise were subjected to exercise stress tests, both before and after intravenous infusion of 2 mg/kg flecainide. The in vitro effects of flecainide were evaluated using the patch-clamp technique with HEK293 cells expressing the Nav 1.5 channel. RESULTS: The flecainide treatment significantly reduced the frequency of PVCs during and after exercise. Next, the sensitivity of the p.I141V mutant channel to flecainide was compared to that of the wild type channel. Perfusion of flecainide inhibited the peak and window currents in both groups. CONCLUSION: The clinical investigations of the affected patients, as well as the molecular and pharmacological characterization of the SCN5A p.I141V mutation, provide new evidence supporting the association of this mutation with exercise-induced polymorphic ventricular arrhythmias. These data also demonstrate that flecainide may serve as an effective treatment for the defect in Nav 1.5 that leads to an increased sodium window current.

Assessment of myocardial infarct size with body surface potential mapping: validation against contrast-enhanced cardiac magnetic resonance imaging.

BACKGROUND: Assessment of myocardial infarct (MI) size is important for therapeutic and prognostic reasons. We used body surface potential mapping (BSPM) to evaluate whether single-lead electrocardiographic variables can assess MI size. METHODS: We performed BSPM with 120 leads covering the front and back chest (plus limb leads) on 57 patients at different phases of MI: acutely, during healing, and in the chronic phase. Final MI size was determined by contrast-enhanced cardiac magnetic resonance imaging (DE-CMR) and correlated with various computed depolarization- and repolarization-phase BSPM variables. We also calculated correlations between BSPM variables and enzymatic MI size (peak CK-MBm). RESULTS: BSPM variables reflecting the Q- and R wave showed strong correlations with MI size at all stages of MI. R width performed the best, showing its strongest correlation with MI size on the upper right back, there representing the width of the "reciprocal Q wave" (r = 0.64-0.71 for DE-CMR, r = 0.57-0.64 for CK-MBm, P < 0.0001). Repolarization-phase variables showed only weak correlations with MI size in the acute phase, but these correlations improved during MI healing. T-wave variables and the QRSSTT integral showed their best correlations with DE-CMR defined MI size on the precordial area, at best r = -0.57, P < 0.0001 in the chronic phase. The best performing BSPM variables could differentiate between large and small infarcts at all stages of MI. CONCLUSIONS: Computed, single-lead electrocardiographic variables can estimate the final infarct size at all stages of MI, and differentiate large infarcts from small.

The Long-Term Multicenter Observational Study of Dabigatran Treatment in Patients With Atrial Fibrillation (RELY-ABLE) Study.

BACKGROUND: During follow-up of between 1 and 3 years in the Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) trial, 2 doses of dabigatran etexilate were shown to be effective and safe for the prevention of stroke or systemic embolism in patients with atrial fibrillation. There is a need for longer-term follow-up of patients on dabigatran and for further data comparing the 2 dabigatran doses. METHODS AND RESULTS: Patients randomly assigned to dabigatran in RE-LY were eligible for the Long-term Multicenter Extension of Dabigatran Treatment in Patients with Atrial Fibrillation (RELY-ABLE) trial if they had not permanently discontinued study medication at the time of their final RE-LY study visit. Enrolled patients continued to receive the double-blind dabigatran dose received in RE-LY, for up to 28 months of follow up after RE-LY (median follow-up, 2.3 years). There were 5851 patients enrolled, representing 48% of patients originally randomly assigned to receive dabigatran in RE-LY and 86% of RELY-ABLE-eligible patients. Rates of stroke or systemic embolism were 1.46% and 1.60%/y on dabigatran 150 and 110 mg twice daily, respectively (hazard ratio, 0.91; 95% confidence interval, 0.69-1.20). Rates of major hemorrhage were 3.74% and 2.99%/y on dabigatran 150 and 110 mg (hazard ratio, 1.26; 95% confidence interval, 1.04-1.53). Rates of death were 3.02% and 3.10%/y (hazard ratio, 0.97; 95% confidence interval, 0.80-1.19). Rates of hemorrhagic stroke were 0.13% and 0.14%/y. CONCLUSIONS: During 2.3 years of continued treatment with dabigatran after RE-LY, there was a higher rate of major bleeding with dabigatran 150 mg twice daily in comparison with 110 mg, and similar rates of stroke and death.

Dronedarone in high-risk permanent atrial fibrillation.

BACKGROUND: Dronedarone restores sinus rhythm and reduces hospitalization or death in intermittent atrial fibrillation. It also lowers heart rate and blood pressure and has antiadrenergic and potential ventricular antiarrhythmic effects. We hypothesized that dronedarone would reduce major vascular events in high-risk permanent atrial fibrillation. METHODS: We assigned patients who were at least 65 years of age with at least a 6-month history of permanent atrial fibrillation and risk factors for major vascular events to receive dronedarone or placebo. The first coprimary outcome was stroke, myocardial infarction, systemic embolism, or death from cardiovascular causes. The second coprimary outcome was unplanned hospitalization for a cardiovascular cause or death. RESULTS: After the enrollment of 3236 patients, the study was stopped for safety reasons. The first coprimary outcome occurred in 43 patients receiving dronedarone and 19 receiving placebo (hazard ratio, 2.29; 95% confidence interval [CI], 1.34 to 3.94; P=0.002). There were 21 deaths from cardiovascular causes in the dronedarone group and 10 in the placebo group (hazard ratio, 2.11; 95% CI, 1.00 to 4.49; P=0.046), including death from arrhythmia in 13 patients and 4 patients, respectively (hazard ratio, 3.26; 95% CI, 1.06 to 10.00; P=0.03). Stroke occurred in 23 patients in the dronedarone group and 10 in the placebo group (hazard ratio, 2.32; 95% CI, 1.11 to 4.88; P=0.02). Hospitalization for heart failure occurred in 43 patients in the dronedarone group and 24 in the placebo group (hazard ratio, 1.81; 95% CI, 1.10 to 2.99; P=0.02). CONCLUSIONS: Dronedarone increased rates of heart failure, stroke, and death from cardiovascular causes in patients with permanent atrial fibrillation who were at risk for major vascular events. Our data show that this drug should not be used in such patients. (Funded by Sanofi-Aventis; PALLAS ClinicalTrials.gov number, NCT01151137.).

The atrial fibrillation epidemic is approaching the physician's door: will mobile technology improve detection?

The rising numbers of people with atrial fibrillation (AF) carry a heavy toll on our graying population. Epidemiological data suggest that AF exists in 1 in 10 individuals aged older than 80 years. The risk of embolic stroke increases along with well-known cardiovascular risk factors. Should there be systematic screening for the elderly? Although 1 in 10 is a huge hit rate in screening for any major illness, the initiative for such programs in AF remains in 'research and development'.At present, cardiologists can utilize implantable loop recorders in patients referred for specialist consultation. Novel technologies are also available, including cloud-based, algorithm-assisted, non-invasive monitoring patches, which allow extended observation periods. What about people in the community without a recognized need for cardiologic investigation? Mobile technology has made detection of pulse irregularity possible without medical attention. Smartphone apps enable opportunistic rhythm monitoring, but true arrhythmias need to be medically verified. AF may be the first common disorder to be effectively screened for by mobile technology. In the spirit of proactive campaigns such as 'Know Your Pulse', we should prepare for rapidly increasing reports of various pulse irregularities.

Characteristics of atrial fibrillation and comorbidities in familial atrial fibrillation.

INTRODUCTION: One-third of lone atrial fibrillation (AF) presents as familial disorder. Heterogeneity of both genetic background and clinical manifestations remains largely uncharacterized. We aimed to evaluate the clinical characteristics and especially the triggering factors of familial AF. METHODS AND RESULTS: Probands were screened from 84 consecutive lone AF patients seen in our tertiary hospital arrhythmia clinic. Those confirmed to have at least 1 first-degree relative with lone AF were included. 12-lead ECG, Holter recording, and cardiac ultrasound were performed. Data concerning arrhythmias and other medical history were collected. Altogether 17 kindreds with 59 AF patients, 52 of whom had lone AF, were identified. Initiation of AF was atrial extrasystolia (PACs) related in 35%, and vagal or sympathetic in 30% of cases. Within any given family, the characteristics related to AF initiation were the same in two-thirds of kindreds. AV conduction abnormalities were found in 2 families, sinus node dysfunction in 2 families, and both in 3 families. Frequent premature ventricular complexes (>1,000/24 hours) were observed in 9 families. Additional comorbidities included dilative cardiomyopathy and sudden death in 3 families. CONCLUSIONS: In familial AF the proportion of PACs-related AF is lower than expected. The arrhythmia triggers for lone AF in general are heterogeneous but often family specific. Concomitant rhythm disorders, as well as cardiomyopathies, are common in patients with familial AF. A positive family history for AF in an apparently lone AF patient may be a marker for wider spectrum of cardiac pathology.

Electromagnetic interference with cardiac pacemakers and implantable cardioverter-defibrillators from low-frequency electromagnetic fields in vivo.

AIMS: Electromagnetic interference (EMI) can pose a danger to workers with pacemakers and implantable cardioverter-defibrillators (ICDs). At some workplaces electromagnetic fields are high enough to potentially inflict EMI. The purpose of this in vivo study was to evaluate the susceptibility of pacemakers and ICDs to external electromagnetic fields. METHODS AND RESULTS: Eleven volunteers with a pacemaker and 13 with an ICD were exposed to sine, pulse, ramp, and square waveform magnetic fields with frequencies of 2-200 Hz using Helmholtz coil. The magnetic field flux densities varied to 300 µT. We also tested the occurrence of EMI from an electronic article surveillance (EAS) gate, an induction cooktop, and a metal inert gas (MIG) welding machine. All pacemakers were tested with bipolar settings and three of them also with unipolar sensing configurations. None of the bipolar pacemakers or ICDs tested experienced interference in any of the exposure situations. The three pacemakers with unipolar settings were affected by the highest fields of the Helmholtz coil, and one of them also by the EAS gate and the welding cable. The induction cooktop did not interfere with any of the unipolarly programmed pacemakers. CONCLUSION: Magnetic fields with intensities as high as those used in this study are rare even in industrial working environments. In most cases, employees can return to work after implantation of a bipolar pacemaker or an ICD, after an appropriate risk assessment. Pacemakers programmed to unipolar configurations can cause danger to their users in environments with high electromagnetic fields, and should be avoided, if possible.

U wave features in body surface potential mapping in post-myocardial infarction patients.

BACKGROUND: The data on U wave features in post-myocardial infarction (MI) remain sparse. We employed 120-lead body surface potential mapping (BSPM) to explore the U wave in patients with remote MI. METHODS: Sixty post-MI patients and 46 healthy controls were examined. After signal averaging, the polarity changes of U wave related to the T wave were analyzed, and the spatial and temporal U wave parameters were computed. RESULTS: Four types of patterns based on T and U polarity were recognized. A pattern with positive T and U waves was related to better ventricular function. The study groups did not differ as regards to Tend-Uapex and Tapex-Uapex intervals whereas Uapex-Uend was significantly longer in MI patients (110 ± 20 ms vs. 100 ± 13 ms, P = 0.004). MI patients had significantly higher U wave maximum amplitude (70 ± 30 µV vs. 50 ± 20 µV, P < 0.001), and U integral area (3.96 ± 1.50 µV·s vs. 3.17 ± 0.99 µV·s, P = 0.002), but lower corresponding T wave parameter values, thus resulting into higher U/T maximum amplitude and area ratios (0.16 ± 0.10 vs. 0.09 ± 0.04, P < 0.001; and 0.13 ± 0.06 vs. 0.09 ± 0.03, P < 0.001). In comparison to 12-lead ECG, BSPM covering the entire thorax enhanced the detection of U waves. CONCLUSION: MI tends to increase the U amplitude and prolong the later part of U wave duration thus augmenting the U wave. The size and location of infarction were associated with specific T and U wave polarity patterns.

Predicting recovery of myocardial function by electrocardiography after acute infarction.

BACKGROUND: In acute ischemic left ventricular (LV) dysfunction, distinguishing viable myocardium is clinically important. METHODS: Body surface potential mapping (Electrocardiography [ECG] with 123 leads), was recorded in 62 patients with acute coronary syndrome (ACS). ECG variables were computed from de- and repolarization phases. LV segmental wall motion was assessed by echocardiography acutely and after 1 year. RESULTS: The number of dysfunctional segments (DFS) diminished during follow-up in 37 patients (recovery group) and remained the same or increased in 25 patients (nonrecovery group). Acutely, DFS was 5.7 ± 2.1 versus 4.4 ± 2.4 (P = 0.02), and peak CK-MBm 141 ± 157 versus 156 ± 167 µg/L (P = 0.78) in the recovery versus nonrecovery group. At follow-up, DFS was 1.9 ± 1.7 versus 6.5 ± 2.6 (P < 0.001). The best ECG variable to predict decrease in DFS depended on the region of acute LV dysfunction: The best variable in the left anterior descending region was the integral of the first QRS integral (area under the curve [AUC] 0.82, P = 0.002); in the right coronary artery region, this was the integral of the ST segment (AUC 0.98, P = 0.003); and in the left circumflex region, the area including the ST segment and the T wave (AUC 0.97, P = 0.006). CONCLUSIONS: In ACS patients, computed ECG variables predict recovery of LV function from ischemic myocardial injury, even in the presence of comparable CK-MBm release and LV dysfunction.

Intravenous epinephrine infusion test in diagnosis of catecholaminergic polymorphic ventricular tachycardia.

INTRODUCTION: A test involving intravenous infusion of epinephrine has been proposed as a method alternative to exercise stress test in diagnosis of catecholaminergic polymorphic ventricular tachycardia (CPVT). We aimed at estimating the predictive value of intravenous epinephrine administration in CPVT patients with frequent exercise-induced ventricular ectopy. METHODS AND RESULTS: We recruited 81 subjects, including 25 CPVT-linked ryanodine receptor 2 (RYR2) mutation carriers, 11 genetically undefined CPVT patients, and 45 unaffected family members. All subjects underwent a maximal exercise stress test and an intravenous epinephrine infusion test. Exercise stress test was positive in 25 (31%) patients including 14 of 25 (56%) established RYR2-mutation carriers and all 11 (100%) genetically undefined CPVT patients. Epinephrine infusion induced arrhythmias in 3 (12%) RYR2-mutation carriers, 4 (36%) genetically undefined CPVT patients, and 1 (2%) unaffected family member. A total of 18 exercise stress test positive patients did not respond to intravenous epinephrine administration, whereas only 1 epinephrine test responder had a normal exercise stress test. Thus, if exercise stress test is used as a standard, the sensitivity of the epinephrine infusion test is 28% and specificity is 98%. CONCLUSIONS: Intravenous epinephrine infusion has low sensitivity and may not be considered as an alternative method for a maximal exercise stress test in diagnosis of CPVT.

Interference of low frequency magnetic fields with implantable cardioverter-defibrillators.

OBJECTIVES: The aim of this study was to find the electromagnetic interference (EMI) thresholds for several commonly used implantable cardioverter-defibrillators (ICD). DESIGN: Seventeen ICDs were exposed to magnetic fields with different intensities produced by the Helmholtz coil system. Sinusoidal, pulse, ramp, and square-waveforms with a frequency range of 2 Hz to 1 kHz were used. RESULTS: ICD malfunctions occurred in 11 of the 17 ICDs tested. The ICD malfunctions that occurred were false detections of ventricular tachycardia (6/17 ICDs) and ventricular fibrillation (3/17 ICDs), false detection of atrial tachycardia (4/6 dual chamber ICDs) and tachycardia sensing occurring during atrial or ventricular refractory periods (1/17 ICD). In most cases, no interference occurred at magnetic field levels below the occupational safety limits of the International Commission on Non-Ionizing Radiation Protection (ICNIRP). Nevertheless, some frequencies using sine, ramp or square waveforms did interfere with certain ICDs at levels below these limits. No EMI occurred with any of the ICDs below the ICNIRP limits for public exposure. CONCLUSION: Evaluation of EMI should be part of the risk assessment of an employee returning to work after an ICD implantation. The risk assessment should consider magnetic field intensities, frequencies and waveforms.

T-wave morphology after epinephrine bolus may reveal silent long QT syndrome mutation carriers.

BACKGROUND: Long QT syndrome (LQTS) gene mutation carriers with indeterminate electrocardiogram frequently escape clinical diagnosis. We assessed the use of epinephrine bolus injection in revealing T-wave abnormalities. METHODS: We recruited 30 genotyped asymptomatic LQTS gene carriers with nondiagnostic QT interval and 15 controls. Electrocardiogram was recorded with body surface potential mapping after an intravenous epinephrine bolus. T-wave morphology was determined as normal, biphasic, inverted, bifid, or combined pattern. RESULTS: Long QT syndrome carriers and healthy controls had different T-wave profiles (P = .027). Of controls, 12 (80%) of 15 had no change or biphasic appearance, whereas only 10 (33%) of 30 of LQTS carriers had so. Bifid or combined pattern occurred in 15 (50%) of 30 in LQTS and in 6 (60%) of 10 in the LQT3 subgroup but only in 1 (7%) of 15 of healthy. CONCLUSIONS: Modification of ventricular repolarization with low-dose epinephrine injection helps to distinguish silent LQTS mutation carriers. This concerns also the LQT3 subtype, which may escape tests.

Who are the long-QT syndrome patients who receive an implantable cardioverter-defibrillator and what happens to them?: data from the European Long-QT Syndrome Implantable Cardioverter-Defibrillator (LQTS ICD) Registry.

BACKGROUND: A rapidly growing number of long-QT syndrome (LQTS) patients are being treated with an implantable cardioverter-defibrillator (ICD). ICDs may pose problems, especially in the young. We sought to determine the characteristics of the LQTS patients receiving an ICD, the indications, and the aftermath. METHODS AND RESULTS: The study population included 233 patients. Beginning in 2002, data were collected prospectively. Female patients (77%) and LQT3 patients (22% of genotype positive) were overrepresented; mean QTc was 516±65 milliseconds; mean age at implantation was 30±17 years; and genotype was known in 59% of patients. Unexpectedly, 9% of patients were asymptomatic before implantation. Asymptomatic patients, almost absent among LQT1 and LQT2 patients, represented 45% of LQT3 patients. Patients with cardiac symptoms made up 91% of all study participants, but only 44% had cardiac arrest before ICD implantation. In addition, 41% of patients received an ICD without having first been on LQTS therapy. During follow-up, 4.6±3.2 years, at least 1 appropriate shock was received by 28% of patients, and adverse events occurred in 25%. Appropriate ICD therapies were predicted by age <20 years at implantation, a QTc >500 milliseconds, prior cardiac arrest, and cardiac events despite therapy; within 7 years, appropriate shocks occurred in no patients with none of these factors and in 70% of those with all factors. CONCLUSIONS: Reflecting previous concepts, ICDs were implanted in some LQTS patients whose high risk now appears questionable. Refined criteria for implantation, reassessment of pros and cons, ICD reprogramming, and consideration for other existing therapeutic options are necessary.

Can strain rate imaging predict recovery of contraction after acute myocardial infarction?

AIMS: To assess whether strain rate imaging (SRI) can serve to evaluate myocardial viability in patients with acute coronary syndrome (ACS). METHODS AND RESULTS: In 23 patients with ACS, we measured longitudinal tissue Doppler strain and strain rate values from left ventricular basal, mid, and apical segments (n = 414). These segments were grouped according to their acute end-systolic strain values (S(ES)) into those with normocontraction (S(ES)≤-13%), hypocontraction (S(ES) between -13 and -7%), and severe contraction abnormality (S(ES)>-7%). At 8 months, we evaluated the recovery of contraction: Segments with acutely severe contraction abnormality that improved their strain values to ≤-7% were defined as viable, and those that failed to do so as non-viable. In the acute phase, S(ES), post-systolic strain, as well as systolic, early, and late diastolic strain rate values were significantly better in the viable than in the non-viable segments. Post-systolic strain had the best AUC 0.78, and a cut-off value of -3.8% predicted recovery from severe contraction abnormality with a sensitivity of 85% and specificity of 62%. The transmurality of the infarction, assessed by magnetic resonance imaging with delayed enhancement, was significantly larger in the non-viable than in the viable segments (P = 0.006). Acute global S(ES) and systolic strain rate showed the best correlations with final global S(ES) and global infarction percentage after recovery. CONCLUSION: SRI can serve to evaluate myocardial viability in patients with ACS, and to assess the recovery of segmental as well as global left ventricular function.

Epinephrine bolus test in detecting long QT syndrome mutation carriers with indeterminable electrocardiographic phenotype.

BACKGROUND: In long QT syndrome (LQTS), prolonged and heterogeneous ventricular repolarization predisposes to serious arrhythmias. We examined how QT intervals are modified by epinephrine bolus in mutation carriers of three major LQTS subtypes with indefinite QT interval. METHODS: Genotyped, asymptomatic subjects with LQTS type 1 (LQT1; n = 10; four different KCNQ1 mutations), type 2 (LQT2; n = 10; three different HERG mutations), and type 3 (LQT3; n = 10; four different SCN5A mutations), and healthy volunteers (n = 15) were examined. Electrocardiogram was recorded with body surface potential mapping system. After an epinephrine 0.04 µg/kg bolus QT end, QT apex, and T-wave peak-to-end (Tpe) intervals were determined automatically as average of 12 precordial leads. Standard deviation (SD) of the 12 channels was calculated. RESULTS: Heart rate increased 26 ± 10 bpm with epinephrine bolus, and similarly in all groups. QT end interval lengthened, and QT apex interval shortened in LQTS and normals, leading to lengthening of Tpe interval. However, the lengthening in Tpe was larger in LQTS than in normals (mean 32 vs 18 ms; P < 0.05) and SD of QT apex increased more in LQTS than in normals (mean 23 vs 7 ms; P < 0.01). The increase in Tpe was most pronounced in LQT2, and in SD of QT apex in LQT1 and LQT2. CONCLUSIONS: Abrupt adrenergic stimulation with a moderate dose of exogenous epinephrine affects ventricular repolarization in genotype-specific fashion facilitating distinction from normals. This delicate modification may help in diagnosing electrocardiographically silent mutation carriers when screening LQTS family members.

Prognostic value of changes in the electrocardiographic strain pattern during antihypertensive treatment: the Losartan Intervention for End-Point Reduction in Hypertension Study (LIFE).

BACKGROUND: The presence of the ECG strain pattern of lateral ST depression and T-wave inversion at baseline has been associated with an increased risk of cardiovascular morbidity and mortality; however, the independent predictive value for cardiovascular outcomes of regression versus persistence versus development of new ECG strain during antihypertensive therapy is unclear. METHODS AND RESULTS: ECG strain was evaluated at baseline and after 1 year of therapy in 7409 hypertensive patients in the LIFE study (Losartan Intervention For End-point reduction in hypertension) treated in a blinded manner with atenolol- or losartan-based regimens. During 3.8+/-0.8 years of follow-up after the year 1 ECG, cardiovascular death occurred in 236 patients (3.2%), myocardial infarction in 198 (2.7%), stroke in 313 (4.2%), the LIFE composite end point of these 3 events in 600 (8.1%), sudden death in 92 (1.2%), and death due to any cause in 486 (6.6%). Strain was absent on both baseline and year 1 ECGs in 6323 patients (85.3%), regressed from baseline to year 1 in 245 (3.3%), persisted on both ECGs in 549 (7.4%), and was absent at baseline but developed by year 1 in 292 patients (3.9%). Compared with absence of strain on both ECGs, development of new ECG strain was associated with 2.8- to 4.7-fold higher event rates; patients with regression or persistence of strain had intermediate event rates. In Cox multivariable analyses with adjustment for the known predictive value of in-treatment ECG left ventricular hypertrophy by Cornell product and Sokolow-Lyon voltage, in-treatment systolic and diastolic pressure, randomized treatment, and standard cardiovascular risk factors, development of new ECG strain was independently associated with increased risks of cardiovascular death (hazard ratio [HR] 2.42, 95% confidence interval [CI] 1.56 to 3.76), myocardial infarction (HR 1.95, 95% CI 1.11 to 3.44), stroke (HR 1.98, 95% CI 1.30 to 3.01), the LIFE composite end point (HR 2.05, 95% CI 1.51 to 2.78), sudden cardiac death (HR 2.19, 95% CI 1.06 to 4.53), and all-cause mortality (HR 1.92, 95% CI 1.37 to 2.69), whereas the risk associated with regression or persistence of strain was attenuated. CONCLUSIONS: Development of new ECG strain is associated with an increased risk of cardiovascular morbidity and mortality and of all-cause mortality in the setting of antihypertensive therapy and regression of ECG left ventricular hypertrophy.

A randomized invasive cardiac electrophysiology study of the combined ion channel blocker AZD1305 in patients after catheter ablation of atrial flutter.

BACKGROUND: This study assessed the cardiac electrophysiological and hemodynamic effects of an intravenous infusion of the combined ion channel blocker AZD1305. METHODS: After successful ablation of atrial flutter, patients were randomized to receive placebo (n = 12) or AZD1305 (n = 38) in 4 ascending dose groups. Electrophysiological and hemodynamic measurements were performed before and commencing 20 minutes after start of infusion. RESULTS: Left atrial effective refractory period increased dose and the primary outcome measure increased dose and plasma concentration dependently, with a mean increase of 55 milliseconds in dose group 3. There was a corresponding increase in right atrial effective refractory period of 84 milliseconds. The right ventricular effective refractory period and the paced QT interval also increased dose and concentration dependently, by 59 and 70 milliseconds, respectively, in dose group 3. There were indications of moderate increases of atrial, atrioventricular nodal, and ventricular conduction times. No consistent changes in intracardiac pressures were observed, but there was a small transient decrease in systolic blood pressure. Adverse events were consistent with the study population and procedure, and there were no signs of proarrhythmia despite marked delay in ventricular repolarization in some individuals. CONCLUSIONS: AZD1305 shows electrophysiological characteristics indicative of potential antiarrhythmic efficacy in atrial fibrillation.