Jan P. Amlie

The Jervell and Lange-Nielsen Syndrome Natural History, Molecular Basis, and Clinical Outcome

Background— Data on the Jervell and Lange-Nielsen syndrome (J-LN), the long-QT syndrome (LQTS) variant associated with deafness and caused by homozygous or compound heterozygous mutations on the KCNQ1 or on the KCNE1 genes encoding the IKs current, are still based largely on case reports. Methods and Results— We analyzed data from 186 J-LN patients obtained from the literature (31%) and from individual physicians (69%). Most patients (86%) had cardiac events, and 50% were already symptomatic by age 3. Their QTc was markedly prolonged (557±65 ms). Most of the arrhythmic events (95%) were triggered by emotions or exercise. Females are at lower risk for cardiac arrest and sudden death (CA/SD) (hazard ratio, 0.54; 95% CI, 0.34 to 0.88; P=0.01). A QTc >550 ms and history of syncope during the first year of life are independent predictors of subsequent CA/SD. Most mutations (90.5%) are on the KCNQ1 gene; mutations on the KCNE1 gene are associated with a more benign course. β-Blockers have only partial efficacy; 51% of the patients had events despite therapy and 27% had CA/SD. Conclusions— J-LN syndrome is a most severe variant of LQTS, with a very early onset and major QTc prolongation, and in which β-blockers have limited efficacy. Subgroups at relatively lower risk for CA/SD are identifiable and include females, patients with a QTc ≤550 ms, those without events in the first year of life, and those with mutations on KCNE1. Early therapy with implanted cardioverter/defibrillators must be considered.

Mechanical Dispersion Assessed by Myocardial Strain in Patients After Myocardial Infarction for Risk Prediction of Ventricular Arrhythmia

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.

Left ventricular mechanical dispersion by tissue Doppler imaging: a novel approach for identifying high-risk individuals with long QT syndrome

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.

Right ventricular mechanical dispersion is related to malignant arrhythmias: a study of patients with arrhythmogenic right ventricular cardiomyopathy and subclinical right ventricular dysfunction.

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.

Transmural Differences in Myocardial Contraction in Long-QT Syndrome Mechanical Consequences of Ion Channel Dysfunction

Background— Long-QT syndrome (LQTS) is characterized by prolonged myocardial action potential duration. The longest action potential duration is reported in the endomyocardium and midmyocardium. Prolonged action potential duration in LQTS may cause prolonged cardiac contraction, which can be assessed by strain echocardiography. We hypothesized that myocardial contraction is most prolonged in subendocardial myofibers in LQTS patients and that inhomogeneous transmural contraction is related to the risk of spontaneous arrhythmia. Methods and Results— We included 101 genotyped LQTS mutation carriers and 35 healthy individuals. A history of cardiac arrhythmias was present in 48 mutations carriers, and 53 were asymptomatic. Myocardial contraction duration was assessed by strain echocardiography as time from the ECG Q wave to peak strain in 16 LV segments. Strain was assessed along the longitudinal axis, predominantly representing subendocardial fibers, and along the circumferential axis, representing midmyocardial fibers. Mean contraction duration was longer in LQTS mutation carriers compared with healthy individuals (445±45 versus 390±40 milliseconds; P<0.001) and longer in symptomatic compared with asymptomatic LQTS mutation carriers (460±40 versus 425±45 milliseconds; P<0.001). Contraction duration by longitudinal strain was longer than by circumferential strain in symptomatic LQTS patients (460±45 versus 445±45 milliseconds; P=0.008) but not in asymptomatic patients and healthy individuals, indicating transmural mechanical dispersion. This time difference was present in a majority of LV segments and was most evident in patients with LQT2 and the Jervell and Lange-Nielsen syndrome. Conclusion— Contraction duration in symptomatic LQTS mutation carriers was longer in the subendocardium than in the midmyocardium, indicating transmural mechanical dispersion, which was not present in asymptomatic and healthy individuals.Background— Long-QT syndrome (LQTS) is characterized by prolonged myocardial action potential duration. The longest action potential duration is reported in the endomyocardium and midmyocardium. Prolonged action potential duration in LQTS may cause prolonged cardiac contraction, which can be assessed by strain echocardiography. We hypothesized that myocardial contraction is most prolonged in subendocardial myofibers in LQTS patients and that inhomogeneous transmural contraction is related to the risk of spontaneous arrhythmia. Methods and Results— We included 101 genotyped LQTS mutation carriers and 35 healthy individuals. A history of cardiac arrhythmias was present in 48 mutations carriers, and 53 were asymptomatic. Myocardial contraction duration was assessed by strain echocardiography as time from the ECG Q wave to peak strain in 16 LV segments. Strain was assessed along the longitudinal axis, predominantly representing subendocardial fibers, and along the circumferential axis, representing midmyocardial fibers. Mean contraction duration was longer in LQTS mutation carriers compared with healthy individuals (445±45 versus 390±40 milliseconds; P <0.001) and longer in symptomatic compared with asymptomatic LQTS mutation carriers (460±40 versus 425±45 milliseconds; P <0.001). Contraction duration by longitudinal strain was longer than by circumferential strain in symptomatic LQTS patients (460±45 versus 445±45 milliseconds; P =0.008) but not in asymptomatic patients and healthy individuals, indicating transmural mechanical dispersion. This time difference was present in a majority of LV segments and was most evident in patients with LQT2 and the Jervell and Lange-Nielsen syndrome. Conclusion— Contraction duration in symptomatic LQTS mutation carriers was longer in the subendocardium than in the midmyocardium, indicating transmural mechanical dispersion, which was not present in asymptomatic and healthy individuals. # Clinical Perspective {#article-title-34}

Implantable Cardioverter Defibrillator Dysfunction During and After Magnetic Resonance Imaging

ANFINSEN, O.‐G., et al.: Implantable Cardioverter Defibrillator Dysfunction During and After Magnetic Resonance Imaging. 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.

Long-Term Outcome of Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy A Scandinavian Multicenter Study

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.

The Terminal Part of the QT Interval (T peak to T end): A Predictor of Mortality after Acute Myocardial Infarction

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.

Long-Term Outcome of Percutaneous Transluminal Septal Myocardial Ablation in Hypertrophic Obstructive Cardiomyopathy

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.

The activation of platelet function, coagulation, and fibrinolysis during radiofrequency catheter ablation in heparinized patients.

Hemostatic Activation during RF Ablation. Introduction: Catheter ablation may be complicated by clinical thromboembolism in about 1% of patients.