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Objective: Late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging is the reference standard for non-invasive assessment of fibrosis. In hypertrophic cardiomyopathy (HCM) patients the histological substrate for LGE is still unknown. The aim of this study was to assess the ability of LGE and strain echocardiography to detect type and extent of myocardial fibrosis in obstructive HCM patients undergoing septal myectomy., Methods: Thirty-two HCM patients (age 60±10) were included in this cross-sectional study and preoperatively examined by speckle-tracking strain echocardiography and LGE-CMR (n=21). Histological fibrosis was classified as interstitial, replacement and total., Results: Histological fibrosis was present in 31 patients. The percentage of total, interstitial and replacement fibrosis was 15(7, 31)%, 11(5, 24)% and 3(1, 6)%, respectively. Reduced longitudinal septal strain correlated with total (r=0.50, p=0.01) and interstitial (r=0.40, p=0.03), but not with replacement fibrosis (r=0.28, p=0.14). Septal LGE was detected in 13/21 (62%), but percentage LGE did not correlate with total fibrosis (r=0.25, p=0.28). Extent of fibrosis did not differ between patients with and without septal LGE (20(9, 58)% versus 14(5, 19)% p=0.41). Patients with ventricular arrhythmias (n=8) had lower septal longitudinal strain and increased extent total and interstitial fibrosis in myectomy specimens, but no differences were demonstrated in LGE. Reduced longitudinal septal strain and increased extent of interstitial fibrosis predicted ventricular arrhythmias independently of age and gender., Conclusions: In myectomised HCM patients, reduced longitudinal septal strain correlated better with interstitial and total fibrosis in myectomy specimens, and was a more powerful tool to predict arrhythmias than LGE.

Background: The long QT syndrome (LQTS) is an inherited cardiac channelopathy associated with syncope and sudden cardiac death due to ventricular arrhythmias. It is most frequently caused by potassium channel mutations. Potassium channels are also expressed in brain tissue and play an important role in idiopathic epilepsies. Recent reports have indicated that related potassium channel mutations may coexpress as concomitant epilepsy and LQTS., Objective: The purpose of this study was to explore cerebral activity by means of EEG recordings in individuals with LQTS related to potassium channel mutations., Methods: Seventeen individuals with confirmed LQTS related to potassium channel mutations (11 LQT1 and 6 LQT2) were prospectively studied with 21-channel electroencephalography (EEG) LQTS -related symptoms, comorbidity, medication, and QTc (12-lead ECG) were recorded. Sixteen healthy individuals previously studied with EEG served as a control group. All EEGs were reviewed by two independent neurophysiologists., Results: EEG recordings were abnormal in 12 of 17 patients (71%) in the LQTS group, whereas abnormalities were present in only 2 of 16 healthy controls (13%; P <.01). In the LQTS group, all abnormal EEGs showed a combination of theta activity and sharp waves. Two patients showed additional delta activity. None of the patients had definite epileptic activity (spikes, spike waves)., Conclusion: Abnormal electrical cerebral activity was identified more frequently in subjects with LQTS secondary to a potassium channel mutation compared with healthy controls. This result indicates a possible link between cardiac and cerebral channelopathy., (© 2013 Heart Rhythm Society Published by Heart Rhythm Society All rights reserved.)

Objectives: Better tools are needed for detection of future malignant ventricular arrhythmias post myocardial infarct (MI). Wedensky Modulation (WM) is a new semi-invasive method: A short low-amplitude electrical impulse is applied synchronized to the QRS between a precordial and dorsal thoracic patch, and changes in the following QRS-T are registered., Design: A total of 357 (MI) ICD patients underwent WM testing. QRS-T wavelet analysis provided WM Indexes for the QRS complex (WMI-R) and T wave (WMI-T). Outcome was the time to first occurrence of appropriate device therapy for ventricular arrhythmia. Patients were followed at 6-month intervals for 2 years., Results: No arrhythmia was induced by the testing. Two-year appropriate arrhythmia treatment occurred in 35% (WMI-R positive) versus 25% (WMI-R negative, p = 0.014), and. 45% versus 26% (p = 0.001) for WMI-T positive versus negative. Two-year event rates of WMI-R or WMI-T positive versus WMI-R and WMI-T negative were 36% versus 22% (p = 0.004). In Cox proportional hazard model, the combination of WMI-R and WMI-T was the only statistically significant event predictor (p = 0.003)., Conclusion: Potentially life-threatening ventricular arrhythmic events could be predicted by the WM test. In combination with other risk factors WMI may be useful in these patients.

Aims: Reduced echocardiographic strain is associated with ventricular arrhythmias in hypertrophic cardiomyopathy (HCM) patients. The aim of this cross-sectional study was to investigate which type of histological fibrosis contributes to ventricular arrhythmias and reduced septal longitudinal strain, in obstructive HCM-patients with or without additional coronary artery disease (CAD) and/or hypertension (HT)., Methods and Results: Sixty-three HCM-patients (mean age 57 ± 13 years) were included. Strain by speckle tracking echocardiography was performed prior to either percutaneous transluminal septal ablation (n = 37) or septal myectomy (n = 26). In 24 patients myectomy specimens were available (histology population) and allowed determination of %area of interstitial and replacement fibrosis. Twenty-nine (46%) patients had concomitant CAD and/or HT, and 15 (24%) experienced ventricular arrhythmias defined as documented ventricular tachycardia or arrhythmogenic suspected syncope. The patients with ventricular arrhythmias had lower septal longitudinal strain compared with those without arrhythmias (-9.0 ± 4.0 vs. -13.6 ± 5.6%, P = 0.006). In the histology population reduced septal longitudinal strain correlated to interstitial (R(2) = 0.36 P = 0.003), but not to replacement fibrosis (R(2) = 0.03 P = 0.43). By logistic regression analyses, interstitial fibrosis predicted ventricular arrhythmias (OR 1.16, 95% CI 1.02-1.32, P = 0.03), while replacement fibrosis did not (OR 1.22, 95% CI 0.93-1.59, P = 0.15)., Conclusion: Total amount of fibrosis was a marker of ventricular arrhythmias in obstructive HCM-patients. Interstitial fibrosis seemed to be more important compared with replacement fibrosis in arrhythmogenesis, and was related to reduced septal myocardial function. These findings suggest that interstitial fibrosis may play an important role as the arrhythmogenic substrate, and that strain echocardiography can help detection of patients at risk.

Antiepileptic drugs (AEDs) have been associated with cardiac conduction abnormalities and arrhythmias, predominantly in patients with predisposing cardiac conditions. Ventricular late potentials (VLPs) detected in the signal-averaged electrocardiogram (SAECG) may imply an increased risk of ventricular tachycardia or fibrillation. Twenty-six AED-naïve patients with newly diagnosed epilepsy and no clinical evidence of heart disease were examined with SAECG and standard ECG. Fifteen patients were treated with lamotrigine and ten with carbamazepine. No significant abnormality was found in the standard ECG or SAECG three to nine months after initiation of AED therapy. In one patient, a VLP was detected at baseline and subsequent MRI demonstrated significant right ventricular pathology; therefore, this patient was excluded from the rest of the study. This exclusion along with only newly diagnosed patients with a low total seizure count being included in the study may explain the lack of AED-induced electrocardiographic abnormalities in this patient cohort., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Heart transplant (HTx) recipients usually have reduced exercise capacity with reported VO(2peak) levels of 50-70% predicted value. Our hypothesis was that high-intensity interval training (HIIT) is an applicable and safe form of exercise in HTx recipients and that it would markedly improve VO(2peak.) Secondarily, we wanted to evaluate central and peripheral mechanisms behind a potential VO(2peak) increase. Forty-eight clinically stable HTx recipients >18 years old and 1-8 years after HTx underwent maximal exercise testing on a treadmill and were randomized to either exercise group (a 1-year HIIT-program) or control group (usual care). The mean ± SD age was 51 ± 16 years, 71% were male and time from HTx was 4.1 ± 2.2 years. The mean VO(2peak) difference between groups at follow-up was 3.6 [2.0, 5.2] mL/kg/min (p < 0.001). The exercise group had 89.0 ± 17.5% of predicted VO(2peak) versus 82.5 ± 20.0 in the control group (p < 0.001). There were no changes in cardiac function measured by echocardiography. We have demonstrated that a long-term, partly supervised and community-based HIIT-program is an applicable, effective and safe way to improve VO(2peak) , muscular exercise capacity and general health in HTx recipients. The results indicate that HIIT should be more frequently used among stable HTx recipients in the future., (© Copyright 2012 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Background: The terminal part of the QT interval (T peak to T end; Tp-e)-an index for dispersion of cardiac repolarization-is often prolonged in patients experiencing malignant ventricular arrhythmias after acute myocardial infarction (AMI). We wanted to explore whether high Tp-e might predict mortality or fatal arrhythmia post-AMI., Methods: Tp-e was measured prospectively in 1359/1384 (98.2%) consecutive patients with ST elevation (n = 525) or non-ST elevation (n = 859) myocardial infarction (STEMI or NSTEMI) admitted for coronary angiography., Results: Tp-e was significantly correlated with age, heart rate (HR), heart failure, LVEF, creatinine, three-vessel disease, previous AMI and QRS and QT duration. During a mean follow-up of 1.3 years (range 0.4-2.3),109 patients (7.9%) died; 25, 45, and 39 from cardiac arrhythmia, nonarrhythmic cardiac causes and other causes, respectively. Long Tp-e was strongly associated with increased risk of death, and Tp-e remained a significant predictor of death in multivariable Cox analyses (RR 1.5, 95% CI[1.3-1.7]). HR-corrected Tp-e (cTp-e) was the strongest predictor of death (RR 1.6 [1.4-1.9]). Tp-e and cTp-e were particularly strong predictors of fatal cardiac arrhythmia (RR 1.6 [1.2-2.1] and RR 1.8 [1.4-2.4]). Findings were similar in STEMI and NSTEMI. When comparing two methods for measuring Tp-e, one including the tail of the T wave and one not, the former had markedly higher predictive power (P < 0.001)., Conclusion: Tp-e, and in particular cTp-e, were strong predictors of mortality during the first year post-AMI, and should be further evaluated as prognostic factors additional to established post-AMI risk factors., (© 2012, Wiley Periodicals, Inc.)

Background: Single-center reports on percutaneous transluminal septal myocardial ablation (PTSMA) in patients with hypertrophic obstructive cardiomyopathy have shown considerable differences in outcome., Methods and Results: We report the long-term outcome of 313 PTSMA procedures performed in 279 patients with hypertrophic obstructive cardiomyopathy aged 59±14 years from 1999 to 2010 in 4 Scandinavian centers. Sixty-nine percent of patients had ≥1 comorbidity at baseline. The median (interquartile range) of left ventricular outflow tract gradient at rest was reduced from 58 mm Hg (34 to 89 mm Hg) at baseline to 12 mm Hg (8 to 24 mm Hg) at 1-year (P<0.001) and during Valsalva maneuver from 93 mm Hg (70 to 140 mm Hg) to 21 mm Hg (11 to 42 mm Hg) (P<0.001). The proportion of patients with syncope was reduced from 18% to 2% (P<0.001), and the proportion in New York Heart Association class III/IV was reduced from 94% to 21% (P<0.001). All treatment effects remained stable during the follow-up. New York Heart Association class III/IV at the most recent follow-up (2.9±2.6 years) was associated with diabetes mellitus (P=0.03), chronic obstructive pulmonary disease (P=0.02), and valve disease unrelated to hypertrophic cardiomyopathy (P<0.01). In-hospital mortality was 0.3%. The 1-, 5- and 10-year survival rates were 97%, 87%, and 67%, respectively (P=0.06 versus an age- and sex-matched background population) in all patients and 99%, 94%, and 88%, respectively (P=0.12) in patients aged <60 years (48±9 years, n=141). Age (hazard ratio, 1.07; 95% CI, 1.03 to 1.1) was the only predictor of survival., Conclusions: In this multicenter study, the in-hospital mortality after PTSMA was low despite considerable comorbidities. The hemodynamic and symptomatic effects were sustained long term. The long-term symptomatic outcome was associated with baseline comorbidities. The 10-year survival rate was comparable to that in an age- and sex-matched background population, and age was the only predictor of survival.

Aims: We evaluated if right ventricular (RV) mechanical dispersion by strain was related to ventricular arrhythmias (VT/VF) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) and if mechanical dispersion was increased in so far asymptomatic mutation carriers., Methods and Results: We included 69 patients, 42 had symptomatic ARVC and 27 were mutation positive asymptomatic family members. Forty healthy individuals served as controls. Myocardial strain was assessed in 6 RV and 16 left ventricular (LV) segments. Contraction duration (CD) in 6 RV and 16 LV segments were measured as the time from onset R on electrocardiogram to maximum myocardial shortening in each segment. The standard deviation of CD was defined as mechanical dispersion. Mechanical dispersion was more pronounced in ARVC patients with arrhythmias compared with asymptomatic mutation carriers and healthy individuals in RV [52(41,63) vs. 35(23,47) vs. 13(9,19)ms, P < 0.001]. Mechanical dispersion was more pronounced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001). Right ventricular mechanical dispersion predicted VT/VF in a multivariate logistic regression analysis [odds ratio (OR), 1.66 (95% confidence interval (CI) 1.06-2.58), P < 0.03]. Right ventricular and LV function by strain were reduced in symptomatic ARVC patients and correlated significantly (R = 0.81, P < 0.001). Right ventricular and LV strain were reduced in asymptomatic mutation carriers compared with healthy individuals (P < 0.001)., Conclusion: Right ventricular mechanical dispersion was pronounced in patients with ARVC with VT/VF. Right ventricular mechanical dispersion was present in asymptomatic mutation carriers and may be helpful in risk stratification. Right ventricular and LV function correlated in ARVC patients implying that ARVC is a biventricular disease.

A major challenge in current cardiology is to predict who will die suddenly from ventricular arrhythmias. Ventricular arrhythmias are the most common cause of sudden cardiac death, occurring in about 1-2:1,000 inhabitants yearly, and is most frequently due to coronary artery disease. Patients with increased risk of ventricular arrhythmias can be offered medical treatment and ultimately an implantable cardioverter defibrillator (ICD). Left ventricular ejection fraction (EF) is currently the main risk stratification tool used to select patients for ICD therapy. However, EF is insufficient in predicting arrhythmic risk. A number of techniques have been presented to improve arrhythmic risk stratification without having reached clinical utility. Conduction abnormalities and dispersion of action potential duration forms the substrate for malignant ventricular arrhythmias in infarcted tissue as in several cardiomyopathies. The ability to assess electrical dispersion in patients noninvasively has been limited. Myocardial strain by echocardiography has been presented as an accurate tool for assessing myocardial function and timing. Inhomogeneous and dispersed myocardial contraction has been related to the occurrence of ventricular arrhythmias and seems to be a promising tool in risk stratification. This review focuses on arrhythmia mechanisms and novel echocardiographic tools for assessing risk of ventricular arrhythmias., (Copyright © 2011 S. Karger AG, Basel.)

Aim: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited cardiac disease predisposing to life-threatening arrhythmias. We aimed to determine the prevalence of arrhythmias and efficacy of beta-blocker treatment in mutation-positive family members diagnosed by cascade genetic screening., Methods and Results: Relatives of six unrelated CPVT patients were tested for the relevant mutation in the ryanodine receptor-2 gene. Mutation carriers underwent an exercise test at inclusion time and 3 months after the initiation of beta-blocker therapy in the highest tolerable dose. The occurrence of ventricular premature beats, couplets, and non-sustained ventricular arrhythmias (nsVT) were recorded in addition to the heart rate at which they occurred. Thirty family members were mutation carriers and were followed for 22 (13-288) months. Previous undiagnosed CPVT-related symptoms were reported by eight subjects. Exercise test induced ventricular arrhythmias in 23 of the 30 mutation carriers. On beta-blocker treatment, exercise-induced arrhythmias occurred at a lower heart rate (117 +/- 17 vs. 135 +/- 34 beats/min, P = 0.02) but at similar workload (P = 0.78). Beta-blocker treatment suppressed the occurrence of exercise-induced nsVT in three of the four patients, while less severe arrhythmias were unchanged. One patient died during follow-up., Conclusion: Exercise test revealed a high prevalence of arrhythmias in CPVT mutation carriers diagnosed by cascade genetic screening. beta-Blocker therapy appeared to suppress the most severe exercise-induced arrhythmias, while less severe arrhythmias occurred at a lower heart rate.

Objectives: The aim of this study was to investigate whether myocardial strain echocardiography can predict ventricular arrhythmias in patients after myocardial infarction (MI)., Background: Left ventricular (LV) ejection fraction (EF) is insufficient for selecting patients for implantable cardioverter-defibrillator (ICD) therapy after MI. Electrical dispersion in infarcted myocardium facilitates malignant arrhythmia. Myocardial strain by echocardiography can quantify detailed regional and global myocardial function and timing. We hypothesized that electrical abnormalities in patients after MI will lead to LV mechanical dispersion, which can be measured as regional heterogeneity of contraction by myocardial strain., Methods: We prospectively included 85 post-MI patients, 44 meeting primary and 41 meeting secondary ICD prevention criteria. After 2.3 years (range 0.6 to 5.5 years) of follow-up, 47 patients had no and 38 patients had 1 or more recorded arrhythmias requiring appropriate ICD therapy. Longitudinal strain was measured by speckle tracking echocardiography. The SD of time to maximum myocardial shortening in a 16-segment LV model was calculated as a parameter of mechanical dispersion. Global strain was calculated as average strain in a 16-segment LV model., Results: The EF did not differ between ICD patients with and without arrhythmias occurring during follow-up (34 +/- 11% vs. 35 +/- 9%, p = 0.70). Mechanical dispersion was greater in ICD patients with recorded ventricular arrhythmias compared with those without (85 +/- 29 ms vs. 56 +/- 13 ms, p < 0.001). By Cox regression, mechanical dispersion was a strong and independent predictor of arrhythmias requiring ICD therapy (hazard ratio: 1.25 per 10-ms increase, 95% confidence interval: 1.1 to 1.4, p < 0.001). In patients with an EF >35%, global strain showed better LV function in those without recorded arrhythmias (-14.0% +/- 4.0% vs. -12.0 +/- 3.0%, p = 0.05), whereas the EF did not differ (44 +/- 8% vs. 41 +/- 5%, p = 0.23)., Conclusions: Mechanical dispersion was more pronounced in post-MI patients with recurrent arrhythmias. Global strain was a marker of arrhythmias in post-MI patients with relatively preserved ventricular function. These novel parameters assessed by myocardial strain may add important information about susceptibility for ventricular arrhythmias after MI., (Copyright 2010 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: CPVT (catecholaminergic polymorphic ventricular tachycardia) is a condition characterized by syncopes and cardiac arrest that was first described in 1975. CPVT has later been classified as a genetic disease with a great risk for life-threatening arrhythmias that are mainly caused by mutations in the ryanodine receptor 2 gene. Starting with a case report, we present an overview of CPVT., Material and Methods: The literature reviewed was identified through a non-systematic search in PubMed., Results: Diagnosing CPVT may be difficult, as resting ECG is normal and the syncopes may be misdiagnosed as epilepsy. Information about syncopes related to physical or emotional stress and occurrence of unexplained syncopes or cardiac arrest among family members, is important in the diagnostic evaluation. An exercise stress test often reveals the classical pattern of ventricular arrhythmias at heart rates above 100 beats/min. The diagnosis can be confirmed by genetic testing. By beta-blocker treatment and, if necessary, an ICD (implantable cardioverter defibrillator) the prognosis can be improved., Interpretation: CPVT is a serious disease with a poor prognosis when left untreated. It is a rare but important differential diagnosis in young individuals with syncopes or cardiac arrest. Genetic screening of relatives has made it possible to identify mutation carriers in affected families in order to provide them with preventive therapy.

Purpose: To investigate the comparative effects of carbamazepine (CBZ) and lamotrigine (LTG) on electrocardiography (ECG) parameters in elderly patients with newly diagnosed epilepsy., Methods: The study was conducted in the Norwegian subcohort (n = 108) of an international randomized double-blind 40-week trial, which compared the efficacy and tolerability of LTG and sustained-release CBZ in patients aged 65 and older with newly diagnosed epilepsy. Target maintenance doses were 400 mg/day for CBZ and 100 mg/day for LTG, with adjustments based on clinical response. Patients with significant unpaced atrioventricular (AV) conduction defect were excluded. Resting 12-lead ECG recordings were made under standardized conditions at pretreatment (baseline) and at the 40-week study visit (treatment visit). Changes in QRS interval (primary endpoint), heart rate (HR), PQ, and QTc (HR-corrected QT) intervals were assessed and compared between groups., Results: Of the 108 patients randomized, 33 discontinued prematurely because of adverse events (n = 24, none of which was cardiac) or other reasons (n = 9), and 15 were nonevaluable due to incomplete ECG data. None of the assessed ECG parameters differed significantly between groups at baseline. No significant ECG changes were recorded between baseline and treatment visit for QRS duration and QTc intervals, whereas HR fell and PQ intervals increased slightly on both treatments. However, there were no differences between groups in changes from baseline to treatment visit. There were no significant relationships between individual ECG changes and serum drug concentrations, except for QTc intervals, which decreased slightly with increasing CBZ concentrations. The proportion of patients with ECG parameters outside the normal range at treatment visit was similar to that recorded at baseline., Discussion: Clinically significant ECG changes are not common during treatment with CBZ or LTG in elderly patients with no preexisting significant AV conduction defects.

An increasing number of genetic tests for cardiomyopathies are becoming available for clinical use. This commentary will give a short overview of indications and challenges concerning genetic testing for these conditions.

Aims: The aim of this study was to investigate whether prolonged and dispersed myocardial contraction duration assessed by tissue Doppler imaging (TDI) may serve as risk markers for cardiac events (documented arrhythmia, syncope, and cardiac arrest) in patients with long QT syndrome (LQTS)., Methods and Results: Seventy-three patients with genetically confirmed LQTS (nine double- and 33 single-mutation carriers with previous cardiac events and 31 single-mutation carriers without events) were studied. Myocardial contraction duration was prolonged in each group of LQTS patients compared with 20 healthy controls (P < 0.001). Contraction duration was longer in single-mutation carriers with previous cardiac events compared with those without (0.46 +/- 0.06 vs. 0.40 +/- 0.06 s, P = 0.001). Prolonged contraction duration could better identify cardiac events compared with corrected QT (QTc) interval in single-mutation carriers [area under curve by receiver-operating characteristic analysis 0.77 [95% confidence interval (95% CI) 0.65-0.89] vs. 0.66 (95% CI 0.52-0.79)]. Dispersion of contraction was more pronounced in single-mutation carriers with cardiac events compared with those without (0.048 +/- 0.018 vs. 0.031 +/- 0.019 s, P = 0.001)., Conclusion: Dispersion of myocardial contraction assessed by TDI was increased in LQTS patients. Prolonged contraction duration was superior to QTc for risk assessment. These new methods can easily be implemented in clinical routine and may improve clinical management of LQTS patients.

Mutations in the KCNQ1, HERG, SCN5A, minK and MiRP1 genes cause long QT syndrome (LQTS), of which there are two forms: the Romano Ward syndrome and the Jervell and Lange-Nielsen syndrome. We have performed DNA sequencing of the LQTS-associated genes in 169 unrelated patients referred for genetic testing with respect to Romano Ward syndrome and in 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome. A total of 37 different mutations in the 5 genes, of which 20 were novel, were identified. Among patients with the most stringent clinical criteria of Romano Ward syndrome, a mutation was identified in 71%. Twelve of the 13 unrelated patients referred for genetic testing with respect to Jervell and Lange-Nielsen syndrome were provided with a molecular genetic diagnosis. Cascade genetic screening of 505 relatives of index patients with molecularly defined LQTS identified 251 mutation carriers. The observed penetrance was 41%. Although caution must be exerted, the prevalence of heterozygotes for mutations in the LQTS-associated genes in Norway could be in the range 1/100-1/300, based on the prevalence of patients with Jervell and Lange-Nielsen syndrome.

Haemodynamic abnormalities have been documented in the chronic fatigue syndrome (CFS), indicating functional disturbances of the autonomic nervous system responsible for cardiovascular control. This study was designed to explore the pathophysiology in adolescent CFS-patients by analysing RR-interval (RRI) variability and diastolic blood pressure (DBP) variability during mild orthostatic stress, using an algorithm which accounts for non-stationary biosignals. A total of 27 adolescents with CFS and 33 healthy control subjects having equal age- and sex distribution underwent 15 min of 20 degrees head-up tilt (HUT). The spectral power densities of RRI and DBP were computed in the low-frequency (LF) band (0.04-0.15 Hz) and the high-frequency (HF) band (0.15-0.4 Hz) using an adaptive autoregressive algorithm to obtain a time-varying spectrum. RMSSD, a time domain index of RRI variability, was also computed. At rest, all indices of variability were similar in the two groups. During tilt, CFS patients had a larger increase in the LF/HF ratio (P

We describe the effect of propranolol in an adolescent with chronic fatigue syndrome and orthostatic intolerance. Our observations suggest that the head-up tilt-test and beta-blocker treatment might be considered in patients with chronic fatigue syndrome and that enhanced sympathetic nervous activity might be part of the underlying pathophysiology.

Hemodynamic dysfunction is documented in chronic fatigue syndrome (CFS). This study was conducted to investigate cardiovascular responses to orthostatic stress in adolescents with CFS, using a novel procedure for tilt-table testing. A total of 27 adolescents with CFS and 33 healthy control subjects with equal age and gender distribution underwent 15 minutes of 20 degrees head-up tilt testing. Heart rate, systolic blood pressure (BP), mean BP, diastolic BP, stroke index, total peripheral resistance index, end-diastolic volume index, and acceleration index were continuously and noninvasively recorded. At rest, patients with CFS had higher total peripheral resistance index values (p<0.01) and lower stroke index and end-diastolic volume index values (p<0.05) than controls. During 20 degrees head-up tilt testing, patients with CFS had greater increases in heart rate, diastolic BP (p<0.001), mean BP (p<0.01), and total peripheral resistance index (p<0.05) than controls and greater decreases in stroke index (p<0.05). Syncope or near syncope was not observed. In conclusion, this study found that adolescents with CFS have significant abnormalities of cardiovascular regulation in response to mild orthostatic stress, differentiating them from healthy controls.

Background: Long QT syndrome is characterised by inherited long QT interval on the ECG and increased risk for syncope and sudden death caused by arrhythmias. For Romano-Ward syndrome and Jervell and Lange-Nielsen syndrome DNA based diagnostics are available., Materials and Methods: This paper is a summary of our experience with DNA-based diagnostics of LQTS since the autumn of 2003. The diagnostic analyses are performed by sequencing the exons of five genes, KCNQ1, HERG, SCN5A, minK and MiRP1., Results and Interpretations: As of mid-January 2005, 56 probands with long QT syndrome have been referred for genetic testing. We have identified an underlying mutation in 64% of the patients. Mutations in the KCNQ1 gene are most frequent in Norwegian long QT syndrome patients, as 61% of the patients have their mutation in this gene. The detection of a mutation in the probands has led to genetic testing of 215 relatives; 99 out of these are heterozygous for the mutation present in the family. Heterozygous patients have been referred to a cardiologist. Of the 43 that have been referred to follow up at the department of cardiology at Rikshospitalet, 35 have started treatment with beta blockers to reduce the risk of arrhythmias. Thus, DNA-based diagnostics has clinical significance leading to prophylactic treatment of long QT syndrome patients. Compared to evaluation of ECG, which is negative in 30% of mutation carriers, the sensitivity of DNA-based diagnostics of relatives of probands with a known mutation, is close to 1.

Background: Inherited arrhythmogenic disorders are a group of genetically determined diseases characterised by ventricular tachyarrhythmias sometimes leading to sudden death. The molecular bases of these disorders are mutations in genes coding for various cardiac ion channels. The most common cardiac ion channel disease is the long QT syndrome. This syndrome is rare, but probably more common in Norway than previously expected. We have recently started genetic testing for cardiac ion channel disorders at Rikshospitalet University Hospital in Oslo. This review describes the current understanding of the etiology, prognosis and management of cardiac ion channel disorders, based on literature and our own clinical experience., Interpretation: Cardiac ion channel disorders may lead to sudden cardiac death. Prophylactic and life-saving therapies are available for many of these disorders. Therapy and risk stratification depend on the clinical presentation, the ECG pattern, and which gene is mutated. Genetic testing offers the opportunity to exclude individual family members as mutation carriers.

This report describes a patient in whom a MRI of the brain was performed without realizing that an ICD had been implanted 8 days previously. Electromagnetic noise induced during the MRI was detected as ventricular fibrillation and nearly caused inappropriate shocks. Charge time during MRI was prolonged. The battery indicator switched to "end of life," but this was reversed by capacitor reformation. These problems could have been avoided by inactivating the ICD prior to MRI. Three months later, the pacing threshold increased from 0.4 V per 0.5 ms at implantation to 2.8 V per 0.5. It is still uncertain whether radiofrequency current heating at the electrode tip caused the increased pacing threshold or if this would have occurred independently of the MRI. MRI of patients with an active ICD may cause life-threatening complications, and it is unknown if MRI may be safely performed if the ICD is inactivated. Therefore, MRI of patients with an ICD remains contraindicated.

Background: Ibutilide is a novel class III antiarrhythmic agent used for the termination of atrial flutter and atrial fibrillation. It mainly affects membrane potassium currents (IKr) and prolongs the cardiac action potential. This effect is reflected as QT-interval prolongation in the ECG. Drugs that affect IKr-currents are known to cause malignant ventricular arrhythmia., Material and Methods: We report three patients with heart failure where ibutilide triggered malignant ventricular arrhythmias (sustained torsades de pointes)., Results: All patients experienced dramatic haemodynamic deterioration. One patient died because of sustained arrhythmia. Mode of action for ibutilide is described. Precautions that should be observed when using ibutilide are outlined., Interpretation: Ibutilide is contraindicated in patients with heart failure and should be used with caution in patients with ischaemic heart disease or previous myocardial infarction. Ibutilide-induced ventricular arrhythmias may be particularly difficult to treat in patients with heart failure.

RF catheter ablation is complicated by thromboembolism in about 1% of patients. Limited knowledge exists concerning when and how to use anticoagulation or antithrombotic treatment. We studied the activation of coagulation (prothrombin fragment 1 + 2 [PF1 + 2] and D-dimer), platelets (beta-thromboglobulin [beta-TG]) and fibrinolysis (plasmin-antiplasmin complexes [PAP]) during RF ablation of accessory pathways in 30 patients. They were randomized to receive heparin (100 IU/kg, intravenously) (1) immediately after introduction of the femoral venous sheaths (group I) or (2) after the initial electrophysiological study, prior to the delivery of RF current (groups II and III). Group II additionally received saline irrigation of all femoral sheaths. After the initial bolus, 1,000 IU of heparin was supplied hourly in all groups. Within groups II and III, median plasma values of PF1 + 2 and beta-TG more than tripled (P < or = 0.007) during the diagnostic study and gradually declined during heparin administration despite RF current delivery. Median D-dimer tripled (P = 0.005) and PAP doubled (NS) before heparin administration; then both remained around the upper reference values. In the early heparin group, however, PF1 + 2, D-dimer, and PAP did not rise at all, and beta-TG showed only a slight increase towards the end of the procedure. The differences between group I versus groups II and III were statistically significant prior to the first RF current delivery (PF1 + 2, D-dimer, and beta-TG) and by the end of the procedure (PF1 + 2, D-dimer, and PAP). In conclusion, "late" heparin administration allows hemostatic activation during the initial catheterization and diagnostic study. By administering intravenous heparin immediately after introduction of the venous sheaths, hemostatic activation is significantly decreased. Saline irrigation of the venous sheaths added nothing to late heparin administration.

Sudden heart arrest (HA) in the early phase after aorto coronary bypass surgery represents a serious event necessitating resuscitation, and for those who survive usually also an extra stay in the coronary care unit. Since such episodes of heart standstill may be related to conduction defects, a study was conducted to determine whether the duration of the QRS complex on the preoperative ECG is a marker for this morbid event. A cohort of 1011 consecutive patients operated on between 1982 and 1986 and followed to January 1st, 1993 were included in the study. Incidence of lethal or non-lethal HA during the first 4 weeks after surgery was considered as the primary endpoint and total mortality as the secondary endpoint. The incidence of HA was 40/1011 = 4%, with the majority of events (60%) being lethal. Independent risk factors of HA using the multivariate logistic model were previous coronary artery bypass surgery, presence of mitral regurgitation, left ventricular ejection fraction and the intraoperative cross-clamp time of aorta. Adjusting for the effect of confounder variables showed that the gradient effect of QRS complex duration on the endpoint HA was still present (p = 0.012). The duration of the QRS complex taken from the preoperative ECG had a gradient effect on the incidence of HA. With a baseline level of QRS <70 ms, the following odds ratios (OR) for HA were found: OR = 1.38 (95% CI 0.60-3.31) for QRS 70-80 ms; OR = 2.27 (95% CI 0.87-5.90) for QRS >90-120 ms; and OR = 3.38 (95% CI 1.06-11.50) for QRS > 120 ms, when adjusting for the risk factors. Cumulative survival at 5 years after surgery was 28+/-7.1% for patients experiencing HA versus 87+/-1.2% for patients free from this event. Our results underline the importance of the QRS complex duration as a preoperative marker for HA after aorta coronary bypass surgery, when adjusting for other risk factors. Although the one-year survival is poor for patients experiencing HA, there is no increase in mortality during the late follow-up.

Background: Radiofrequency catheter ablation of atrial flutter, atrial fibrillation or ventricular tachycardia may be favoured by large lesions. We compared lesions created in unipolar mode using 10-mm/8 F electrodes with those of 4-mm/7 F catheters., Methods: Ablations were first performed in porcine hearts in vitro (70 degrees C, 60 s, tangential catheter tip-tissue orientation). Anaesthetized pigs were thereafter ablated with 10- or 4-mm catheters in the right atrial free wall (RAFW), inferior vena cava-tricuspid valve (IVC-TV) isthmus and left ventricle (LV)., Results: In vitro, lesion length doubled and lesion volume tripled using the 10-mm catheter. Average power supply was 69 (SD12) (10-mm tip) versus 26 (SD7) W (4-mm tip). In vivo, lesion length increased by 50% and lesion volume fivefold. Charring at the lesion surface or sudden impedance rises were not observed in vivo. Histologically, coagulation necrosis and minor haemorrhages were found. One RAFW lesion (10-mm) showed a dissection approaching the epicardium. Fibrinous platelet clots or overt thromboses covered the endocardial surface in half of all lesions. Three 10-mm electrode isthmus lesions extended to the right descending posterior artery and one LV lesion to the left anterior descending artery, but there was no damage to the arterial walls. Following six ablations with the 10-mm electrode and two with the 4-mm tip, injury to the adjacent lung tissue of 0.5 to 6.0 mm depth was found (p = 0.22)., Conclusion: RF ablation using 10-mm/8 F electrodes created significantly larger lesions. 10-mm electrodes appeared safe in the porcine IVC-TV isthmus and LV, but not in the RAFW.

Introduction: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients., Methods and Results: We studied the activation of coagulation (prothrombin fragment 1+2 [PF1+2]), platelets (beta-thromboglobulin [beta-TG])) and fibrinolysis (plasmin-antiplasmin complexes [PAP] and D-dimer) during radiofrequency (RF) ablation in 13 patients. They received heparin 100 U/kg intravenously after the initial electrophysiologic study, prior to the delivery of RF current; thereafter 1,000 U/hour throughout the procedure. PF1+2 increased fourfold (P < 0.001) during the diagnostic study, but gradually declined to upper reference value during heparin administration. There was a strong correlation between procedure duration prior to heparin bolus (range 39 to 173 min); and (a) the maximal rise of PF1+2 (r = 0.83, P < 0.001) and (b) the increase of PF1+2 from baseline to end of the procedure (r = 0.74, P = 0.004). There was no correlation between postheparin changes of PF1+2 and (a) postheparin procedure duration (range 40 to 317 min), (b) number of RF pulses (range 1 to 16), or (c) RF current duration (range 46 to 687 sec). Plasma beta-TG concentration showed similar trends. Fibrinolytic activity increased moderately from baseline until heparin administration; then remained around the upper reference values. PAP at the end of procedure and D-dimer at the time of heparin administration both correlated with preheparin procedure duration (r = 0.70, P = 0.007 and r = 0.69, P = 0.01, respectively). All parameters were normal the next morning., Conclusion: Procedure duration prior to heparin administration, and not the delivery of RF current per se, determines activation of hemostasis and fibrinolysis during RF ablation.

Aims: Radiofrequency catheter ablation of atrial flutter and fibrillation may be favoured by large, elongated lesions. We compared bipolar ablation with unipolar ablation from one or two electrodes in the porcine heart., Methods and Results: In vitro, confluent lesions were reliably created by a 'dielectrode' catheter (energy delivered simultaneously (in parallel) from two 4 mm electrodes spaced 1 mm apart, towards an indifferent electrode), and a 'bipolar' catheter (energy delivered (in series) between two 4 mm electrodes spaced 5 mm apart). Sixteen anaesthetized pigs were randomized to standard unipolar (4), dielectrode (6) or bipolar (6) ablation. Two radiofrequency current deliveries of 30 s duration (70 degrees C) were administered to the inferior vena cava-tricuspid valve isthmus and two to the right atrial free wall in all animals. After 4 h, the lesions were examined macroscopically and histologically. Mean (SD) endocardial lesion length x width x depth measured 7.4 (2.4) x 5.4 (2.2) x 2.8 (0.8) mm in the standard unipolar mode, 10.2 (1.4) x 6.3 (0.7) x 3.3 (1.1) mm in the dielectrode mode and 14.0 (3.6) x 6.0 (1.7) x 3.8 (1.2) mm in the bipolar mode. Thus lesion length increased significantly through the three groups (P < 0.001), while width and depth did not., Conclusion: Both dielectrode and bipolar ablation were feasible in porcine right atrial ablation, and created longer lesions than the standard unipolar mode. By allowing a larger interelectrode distance, bipolar ablation created the longest lesions and may be favourable when linear lesions are necessary.

Interruption of atrial flutter and fibrillation by RF catheter ablation may be favored by large, elongated lesions. We administered RF current in unipolar and bipolar mode in porcine right atrium. Bipolar ablation was performed between the tip electrodes of two serially coupled catheters. With 4-mm tip electrodes in vitro, lesion length increased from a mean (SD) of 7.9 (1.2) mm at 3 mm-interelectrode distance (i.e.d.) to 13.3 (3.3) mm at 9-mm IED, but decreased at 12-mm IED due to nonconfluent lesions (P < 0.0001). With 4 mm distal electrodes and 8 mm IED, bipolar lesions were 65% longer than corresponding unipolar ablations. Switching to bipolar mode increased the lesion length more than increasing electrode tip length to 6 mm in unipolar mode. Power and temperature controlled ablation created equally sized lesions. Twelve anesthetized pigs were randomized to unipolar or two catheter bipolar temperature controlled ablation of the right atrial free wall. Bipolar ablation created confluent lesions with endocardial length x width of 13.5 (5.8) x 7.3 (3.7) mm, unipolar ablation 6.4 (2.8) x 4.6 (1.4) mm (P < 0.001 when comparing length and P = 0.013 for lesion width). The atrial lesions in both groups were transmural and extended into hilar lung lesions with maximal depth of 3.0 (1.1) and 2.6 (1.0) mm, respectively (P = 0.44). Five bipolarly and four unipolarly ablated pigs developed right diaphragmal paresis. We conclude that bipolar ablation may be preferable in situations where large, elongated lesions are favorable. The two catheter technique is feasible in porcine right atrium. Both bipolar and unipolar ablation of the porcine right atrial free wall may frequently be complicated by injury to the phrenic nerve and adjacent lung tissue.

Temperature monitoring during RF ablation has been proposed as a means of controlling the creation of the lesion. However, in vivo studies have shown poor correlation between lesion size and catheter tip temperature. Thus, we hypothesized a difference between catheter tip and tissue temperatures during RF catheter ablation, and that this difference may depend on flow passing the ablation site, tip electrode length, and catheter-tissue orientation. In vitro studies were performed using four different ablation catheters (tip electrode length: 2, 4, or 6 mm) with a thermistor or a thermocouple as temperature sensor. Set temperature was 70 degrees C and pulse duration was 30 seconds. Pieces of porcine left ventricle were immersed in a bath of isotonic saline-dextrose solution at 37 degrees C. The ablation catheters were positioned perpendicularly, obliquely, or parallel to the endocardium. A temperature sensor was inserted from the epicardial side and positioned 1 mm beneath the catheter-tissue interface. Experiments were made with a flow of 200 mL/min passing the ablation site or with no flow. The catheter tip and tissue temperatures differed significantly (P < 0.0001) during ablation. This difference increased with time, with flow passing the ablation site, with the length of the tip electrode, and when the catheter was positioned perpendicularly or obliquely to the endocardium as compared to the parallel catheter-tissue orientation (P < 0.05). In conclusion, the tissue temperature may far exceed the catheter tip temperature, and intramyocardial superheating resulting in steam formation and popping may occur despite a relatively low catheter tip temperature.

Reduced heart rate variability (HRV) is an independent risk factor after myocardial infarction, indicating higher risk of fatal and nonfatal arrhythmias and of cardiac death in general. Analysis of HRV is also a valuable tool in clinical research, providing a non-invasive measurement of fluctuations in sympathetic and parasympathetic activation. We expect increased use of these methods, since new 24-hour: ECG-monitoring equipment is to be delivered with software for HRV as an option. Statistical time domain analysis of the whole 24-hour system of recording is very suitable for stratifying risk after myocardial infarction. Frequency domain analysis requires manual as well as automatic editing, but is the method of choice in clinical research involving short-term recordings and standardized conditions.

When radiofrequency catheter ablation of ventricular arrhythmias is unsuccessful, an option may be to combine it with direct current energy. We therefore investigated the effects of such a combination. Radiofrequency energy was delivered in a bipolar or unipolar fashion to the left and right ventricles through an ablation catheter with a tip electrode 2 mm long, using a temperature-guided radiofrequency generator. Radiofrequency ablation was followed by a single cathodal direct current shock (66 J) with the ablation catheter positioned similarly in six closed-chest pigs. In a control group (six animals) only direct current ablation was performed, with one or two energy applications (66 J) in each ventricle. Two of six animals in the radiofrequency/direct current group died due to perforation in the follow-up period, 1 and 3.5 h after the direct current ablation, respectively. Gross pathological examination of the hearts revealed transmural lesions in all animals. In the radiofrequency/direct current group four lesions were perforated, three of which were located in the left ventricle. There was a significant increase in the number of perforations in the radiofrequency/direct current group compared to the control group, where perforation was never observed. Haemorrhagic pericardial fluid was found in five of the six animals in the radiofrequency/direct current group compared to none in the control group. These findings show that myocardial ablation with radiofrequency energy followed by direct current energy in the same session may have a high complication rate.

The aim of the present study was twofold: to assess the safety of ablating the atrial free wall using RF current; and to assess the effect of a single dose of intravenous heparin followed by aspirin once daily to prevent thrombus formation after RF ablation. Temperature and power guided catheter ablation were evaluated. Twenty pigs were randomized to power or temperature guided unipolar RF catheter ablation. Ten animals received a bolus of heparin (150 U/kg) followed by 150-mg aspirin daily, and ten served as controls. A mid-sternal thoracotomy was performed 5-7 days later. The ability of a lesion to resist an increased transmural atrial pressure was examined by inflating a cuff around the pulmonal artery. Transmural lesions were found in all animals. Right atrial pressure was increased from 5 to 30 mmHg with no sign of perforation. In 11 of 20 (55%) animals, 1-3 lesions were found in the lungs (diameter 4-18 mm). The localization of these lesions corresponded to the lesions in the atria. There were no differences in the energy delivery modes with regard to the number of animals with lung lesions. Lesions with thrombus formation were found in four animals in the heparin/aspirin group and in nine animals in the control group. The incidence of thrombi was significantly smaller in the treatment group. There were no differences between temperature and power guided catheter ablation with regard to the size of the atrial lesions or to the incidence of thrombus formation. Transmural lesions induced in the right atrium by RF energy are resistant to increases in transmural pressure. However, lung tissue overlying the ablated target may be injured by the RF energy delivered. The combination of a single dose intravenous heparin followed by aspirin daily may reduce the incidence of thrombus formation.

The authors discuss the potent antiarrhythmic drug amiodarone, with emphasis on indications, efficacy and side effects. At present the drug can be prescribed only by specialists in internal medicine. In order to monitor the efficacy of the drug and any side effects the patient should preferably be evaluated every three to six months. Use of intravenous amiodarone in hospital is effective in many cases but, so far, documentation on this treatment is limited.

The safety and feasibility of temperature-guided radiofrequency (RF) ablation of ventricular myocardium were assessed in an open-chest animal model. RF ablation was performed in the ventricles of 19 pigs using ablation catheters with a tip electrode of 2 or 4 mm length. The energy was delivered in a bipolar (2 mm tip electrode only) or unipolar configuration. Set temperature ranged from 60 to 90 degrees C. Pulse duration was 30 s. Histological examination showed coagulation necrosis with a haemorrhagic zone. However, lesions with a deep cleavage were found after five unipolar (2 mm tip electrode) energy applications. No such lesions were found after unipolar energy applications with a 4 mm tip electrode. During or shortly after ablation, premature ventricular beats and non-sustained VT were frequently observed and in some instances ventricular fibrillation. In the bipolar mode we found a positive correlation between lesion area/volume and peak temperature with a correlation coefficient of 0.48 and 0.56, respectively (P < 0.05). However no correlation was found between lesion size and applied energy. In the unipolar configuration there was no correlation between lesion size and these parameters. Median depth and area were: bipolar: 4.0 mm/23.5 mm2, unipolar (2 mm tip electrode): 3.5 mm/12.2 mm2, unipolar (4 mm tip electrode): 4.0 mm/15.7 mm2. We conclude that in a beating heart it is difficult to predict lesion size from temperature or energy.

Acute coronary syndrome is defined as unstable angina or acute myocardial infarction. A discussion on drug treatment of these conditions was arranged by the Norwegian Society of Cardiology and the Department of Pharmacotherapeutics, University of Oslo, soon after preliminary results of the GISSI II study were available. Relatively simple rules were agreed for the use of analgetics, nitrates and fibrinolytic agents. The last are used only after established myocardial injury. Consensus was also reached on the restricted use of calcium antagonists, inotropic agents and diuretics. There was disagreement concerning the dosage of heparin and the exact use of betablockers, aspirin, warfarin, ACE-inhibitors, magnesium and antiarrhythmics.