Publications by authors named "Lauri Toivonen"

129 Publications

Genealogy and clinical course of catecholaminergic polymorphic ventricular tachycardia caused by the ryanodine receptor type 2 P2328S mutation.

PLoS One 2020 14;15(12):e0243649. Epub 2020 Dec 14.

University of Helsinki, Helsinki, Finland.

Background: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a severe inherited arrhythmic disease associated with a risk of syncope and sudden cardiac death (SCD).

Aims: We aimed at identifying RYR2 P2328S founder mutation carriers and describing the clinical course associated with the mutation.

Methods: The study population was drawn from the Finnish Inherited Cardiac Disorder Research Registry, and from the present genealogical study. Kaplan-Meier graphs, log-rank test and Cox regression model were used to evaluate the clinical course.

Results: Genealogical study revealed a common ancestor couple living in the late 17th century. A total of 1837 living descendants were tested for RYR2 P2328S mutation unveiling 62 mutation carriers aged mean 39±23 years old. No arrhythmic deaths were documented among genotyped subjects, but 11 SCDs were detected in non-genotyped family members since 1970. Three genotyped patients (5%) suffered an aborted cardiac arrest (ACA), and 15 (25%) had a syncope triggered by exercise or stress. Rate of cardiac events was higher among patients who in exercise stress test showed a maximum rate of premature ventricular contractions >30/min (68% vs 17%, p<0.01; hazard ratio = 7.1, p = 0.02), in comparison to patients without the respective finding. A cardioverter-defibrillator (ICD) was implanted to 13 (22%) patients, with an appropriate ICD shock in four (31%) subjects. All ICD shocks, one ACA, and one syncope occurred during β-blocker medication.

Conclusions: Previously undiagnosed CPVT patients may be identified by well-conducted genealogical studies. The RYR2 P2328S mutation causes a potentially severe phenotype, but its expression is variable, thus calling for additional studies on modifying factors.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0243649PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735638PMC
January 2021

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.

BMC Med Genet 2018 04 5;19(1):56. Epub 2018 Apr 5.

Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.

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 β-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 β-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.
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http://dx.doi.org/10.1186/s12881-018-0574-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5887247PMC
April 2018

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.

BMC Cardiovasc Disord 2018 02 8;18(1):27. Epub 2018 Feb 8.

Heart and Lung Center, Helsinki University Hospital and Helsinki University, Haartmaninkatu 4, 00029 HUS, Po BOX 340, Helsinki, Finland.

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.
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http://dx.doi.org/10.1186/s12872-018-0767-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5806273PMC
February 2018

Polymorphisms in the GNAS Gene as Predictors of Ventricular Tachyarrhythmias and Sudden Cardiac Death: Results From the DISCOVERY Trial and Oregon Sudden Unexpected Death Study.

J Am Heart Assoc 2016 11 28;5(12). Epub 2016 Nov 28.

Institute of Pharmacogenetics, University Hospital Essen, Essen, Germany.

Background: Population-based studies suggest that genetic factors contribute to sudden cardiac death (SCD).

Methods And Results: In the first part of the present study (Diagnostic Data Influence on Disease Management and Relation of Genetic Polymorphisms to Ventricular Tachy-arrhythmia in ICD Patients [DISCOVERY] trial) Cox regression was done to determine if 7 single-nucleotide polymorphisms (SNPs) in 3 genes coding G-protein subunits (GNB3, GNAQ, GNAS) were associated with ventricular tachyarrhythmia (VT) in 1145 patients receiving an implantable cardioverter-defibrillator (ICD). In the second part of the study, SNPs significantly associated with VT were further investigated in 1335 subjects from the Oregon SUDS, a community-based study analyzing causes of SCD. In the DISCOVERY trial, genotypes of 2 SNPs in the GNAS gene were nominally significant in the prospective screening and significantly associated with VT when viewed as recessive traits in post hoc analyses (TT vs CC/CT in c.393C>T: HR 1.42 [CI 1.11-1.80], P=0.005; TT vs CC/CT in c.2273C>T: HR 1.57 [CI 1.18-2.09], P=0.002). TT genotype in either SNP was associated with a HR of 1.58 (CI 1.26-1.99) (P=0.0001). In the Oregon SUDS cohort significant evidence for association with SCD was observed for GNAS c.393C>T under the additive (P=0.039, OR=1.21 [CI 1.05-1.45]) and recessive (P=0.01, OR=1.52 [CI 1.10-2.13]) genetic models.

Conclusions: GNAS harbors 2 SNPs that were associated with an increased risk for VT in ICD patients, of which 1 was successfully replicated in a community-based population of SCD cases. To the best of our knowledge, this is the first example of a gene variant identified by ICD VT monitoring as a surrogate parameter for SCD and also confirmed in the general population.

Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00478933.
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http://dx.doi.org/10.1161/JAHA.116.003905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5210425PMC
November 2016

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

Ann Noninvasive Electrocardiol 2016 Jul 7;21(4):343-51. Epub 2015 Oct 7.

Department of Clinical Research, University of Bern, Bern, Switzerland.

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.
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http://dx.doi.org/10.1111/anec.12312DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931835PMC
July 2016

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.

Europace 2016 Oct 24;18(10):1599-1607. Epub 2015 Dec 24.

Division of Cardiology, Heart and Lung Center HUS, Helsinki University Central Hospital, Helsinki, Finland.

Aims: Spontaneous Ca release leads to afterdepolarizations and triggered arrhythmia in catecholaminergic polymorphic ventricular tachycardia (CPVT). Irregular Ca 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 Ca 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 Ca transients in response to isoproterenol. β-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 Ca release by mutant RyR2s as observed in vitro. β-Agonists slow depolarization in RyR2-mutant cells and in CPVT patients. These findings may constitute a marker of arrhythmogenicity.
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http://dx.doi.org/10.1093/europace/euv380DOI Listing
October 2016

Follow-up of 316 molecularly defined pediatric long-QT syndrome patients: clinical course, treatments, and side effects.

Circ Arrhythm Electrophysiol 2015 Aug 10;8(4):815-23. Epub 2015 Jun 10.

From the Heart and Lung Center, Helsinki University Central Hospital (M.K., A.M., M.V., L.T., H.S.), Children's Hospital, Helsinki University Central Hospital (A.H., J.-M.H.), Department of Medicine, Helsinki University Central Hospital (A.M.L., K.K.), and Institute of Behavioural Sciences, Psychology (T.H.), University of Helsinki, Helsinki, Finland; and Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.).

Background: Inherited long-QT syndrome (LQTS) is associated with risk of sudden death. We assessed the clinical course and the fulfillment of current treatment strategies in molecularly defined pediatric LQTS type 1 and (LQT1) and type 2 (LQT2) patients.

Methods And Results: Follow-up data covering a mean of 12 years were collected for 316 genotyped LQT1 and LQT2 patients aged 0 to 18 years. No arrhythmic deaths occurred during the follow-up. Finnish KCNQ1 and KCNH2 founder mutations were associated with fewer cardiac events than other KCNQ1 and KCNH2 mutations (hazard ratio [HR], 0.33; P=0.03 and HR, 0.16; P=0.01, respectively). QTc interval ≥500 ms increased the risk of cardiac events compared with QTc <470 ms (HR, 3.32; P=0.001). Treatment with β-blocker medication was associated with reduced risk of first cardiac event (HR, 0.23; P=0.001). Noncompliant LQT2 patients were more often symptomatic than compliant LQT2 patients (18% and 0%, respectively; P=0.03). Treatment with implantable cardioverter defibrillator was rare (3%) and resulted in reinterventions in 44% of cases.

Conclusions: Severe cardiac events are uncommon in molecularly defined and appropriately treated pediatric LQTS mutation carriers. β-Blocker medication reduces the risk of cardiac events and is generally well tolerated in this age group of LQTS patients.
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http://dx.doi.org/10.1161/CIRCEP.114.002654DOI Listing
August 2015

Follow-up of 316 molecularly defined pediatric long-QT syndrome patients: clinical course, treatments, and side effects.

Circ Arrhythm Electrophysiol 2015 Aug 10;8(4):815-23. Epub 2015 Jun 10.

From the Heart and Lung Center, Helsinki University Central Hospital (M.K., A.M., M.V., L.T., H.S.), Children's Hospital, Helsinki University Central Hospital (A.H., J.-M.H.), Department of Medicine, Helsinki University Central Hospital (A.M.L., K.K.), and Institute of Behavioural Sciences, Psychology (T.H.), University of Helsinki, Helsinki, Finland; and Department of Health, National Institute for Health and Welfare, Helsinki, Finland (A.S.H., V.S.).

Background: Inherited long-QT syndrome (LQTS) is associated with risk of sudden death. We assessed the clinical course and the fulfillment of current treatment strategies in molecularly defined pediatric LQTS type 1 and (LQT1) and type 2 (LQT2) patients.

Methods And Results: Follow-up data covering a mean of 12 years were collected for 316 genotyped LQT1 and LQT2 patients aged 0 to 18 years. No arrhythmic deaths occurred during the follow-up. Finnish KCNQ1 and KCNH2 founder mutations were associated with fewer cardiac events than other KCNQ1 and KCNH2 mutations (hazard ratio [HR], 0.33; P=0.03 and HR, 0.16; P=0.01, respectively). QTc interval ≥500 ms increased the risk of cardiac events compared with QTc <470 ms (HR, 3.32; P=0.001). Treatment with β-blocker medication was associated with reduced risk of first cardiac event (HR, 0.23; P=0.001). Noncompliant LQT2 patients were more often symptomatic than compliant LQT2 patients (18% and 0%, respectively; P=0.03). Treatment with implantable cardioverter defibrillator was rare (3%) and resulted in reinterventions in 44% of cases.

Conclusions: Severe cardiac events are uncommon in molecularly defined and appropriately treated pediatric LQTS mutation carriers. β-Blocker medication reduces the risk of cardiac events and is generally well tolerated in this age group of LQTS patients.
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http://dx.doi.org/10.1161/CIRCEP.114.002654DOI Listing
August 2015

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

BMC Med 2014 Sep 29;12:180. Epub 2014 Sep 29.

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.
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http://dx.doi.org/10.1186/s12916-014-0180-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4180533PMC
September 2014

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

Ann Noninvasive Electrocardiol 2015 May 18;20(3):240-52. Epub 2014 Sep 18.

Division of Cardiology, Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/anec.12198DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6931515PMC
May 2015

Gain-of-function mutation of the SCN5A gene causes exercise-induced polymorphic ventricular arrhythmias.

Circ Cardiovasc Genet 2014 Dec 10;7(6):771-81. Epub 2014 Sep 10.

From the Heart and Lung Center, Helsinki University Central Hospital, Helsinki, Finland (H.S., A.M., L.T.); Department of Clinical Research (M.Y.A., H.A), and Department of Physiology (J.P.K), University of Bern, Bern, Switzerland. and Institute for Molecular Medicine Finland (FIMM), University of Helsinki (J.L., A.P., E.W.), and Department of Medicine, University of Helsinki and Helsinki University Central Hospital (P.J.L.-F., A.M.L., K.K.), Helsinki, Finland.

Background: Over the past 15 years, a myriad of mutations in genes encoding cardiac ion channels and ion channel interacting proteins have been linked to a long list of inherited atrial and ventricular arrhythmias. The purpose of this study was to identify the genetic and functional determinants underlying exercise-induced polymorphic ventricular arrhythmia present in a large multigenerational family.

Methods And Results: A large 4-generation family presenting with exercise-induced polymorphic ventricular arrhythmia, which was followed for 10 years, was clinically characterized. A novel SCN5A mutation was identified via whole exome sequencing and further functionally evaluated by patch-clamp studies using human embryonic kidney 293 cells. Of 37 living family members, a total of 13 individuals demonstrated ≥50 multiformic premature ventricular complexes or ventricular tachycardia upon exercise stress tests when sinus rate exceeded 99±17 beats per minute. Sudden cardiac arrest occurred in 1 individual during follow-up. Exome sequencing identified a novel missense mutation (p.I141V) in a highly conserved region of the SCN5A gene, encoding the Nav1.5 sodium channel protein that cosegregated with the arrhythmia phenotype. The mutation p.I141V shifted the activation curve toward more negative potentials and increased the window current, whereas action potential simulations suggested that it lowered the excitability threshold of cardiac cells.

Conclusions: Gain-of-function of Nav1.5 may cause familial forms of exercise-induced polymorphic ventricular arrhythmias.
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http://dx.doi.org/10.1161/CIRCGENETICS.114.000703DOI Listing
December 2014

Stressful life events and depressive symptoms among symptomatic long QT syndrome patients.

J Health Psychol 2016 Apr 24;21(4):505-12. Epub 2014 Apr 24.

IBS, Psychology, University of Helsinki, Finland.

We examined whether long QT syndrome status moderates the association between stressful life events and depressive symptoms. Participants were 562 (n= 246 symptomatic) long QT syndrome mutation carriers. Depressive symptoms were measured with a modified version of the Beck's Depression Inventory. There was an interaction between long QT syndrome status and stressful life events on depressive symptoms. In the symptomatic long QT syndrome patients, stressful life events were associated with depressive symptoms (B= 0.24, p< 0.001). In the asymptomatic long QT syndrome mutation carriers, this association was 62.5 percent weaker (B= 0.09, p= 0.057). Compared to asymptomatic long QT syndrome mutation carriers, symptomatic long QT syndrome patients are more sensitive to the depressive effects of stressful life events.
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http://dx.doi.org/10.1177/1359105314530450DOI Listing
April 2016

Brief report: Emotional distress and recent stressful life events in long QT syndrome mutation carriers.

J Health Psychol 2015 Nov 11;20(11):1445-50. Epub 2013 Dec 11.

University of Helsinki, Finland.

To study emotional distress in symptomatic and asymptomatic long QT syndrome mutation carriers who had experienced a recent stressful life event. The participants were 209 symptomatic and 279 asymptomatic long QT syndrome mutation carriers. Emotional distress was assessed with the Cope questionnaire and stressful life events with the Social Readjustment Rating Scale. Symptomatic long QT syndrome mutation carriers with burdening recent stressful life events reported a higher emotional distress (β = 0.35, p < 0.001), while the asymptomatic did not show such difference (β = 0.13, p = 0.393). Symptomatic long QT syndrome mutation carriers who have experienced stressful life events recently report an increased emotional distress.
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http://dx.doi.org/10.1177/1359105313513049DOI Listing
November 2015

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

Ann Noninvasive Electrocardiol 2013 Nov 30;18(6):538-46. Epub 2013 Jul 30.

Department of  Cardiology, Helsinki University Central Hospital, Helsinki, Finland; BioMag Laboratory, Helsinki University Central Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/anec.12071DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932261PMC
November 2013

Testing of common electromagnetic environments for risk of interference with cardiac pacemaker function.

Saf Health Work 2013 Sep 20;4(3):156-9. Epub 2013 Jul 20.

Safe New Technologies, Finnish Institute of Occupational Health, Helsinki, Finland.

Background: Cardiac pacemakers are known to be susceptible to strong electromagnetic fields (EMFs). This in vivo study investigated occurrence of electromagnetic interference with pacemakers caused by common environmental sources of EMFs.

Methods: Eleven volunteers with a pacemaker were exposed to EMFs produced by two mobile phone base stations, an electrically powered commuter train, and an overhead high voltage transmission lines. All the pacemakers were programmed in normal clinically selected settings with bipolar sensing and pacing configurations.

Results: None of the pacemakers experienced interference in any of these exposure situations. However, often it is not clear whether or not strong EMFs exist in various work environments, and hence an individual risk assessment is needed.

Conclusions: Modern pacemakers are well shielded against external EMFs, and workers with a pacemaker can most often return to their previous work after having a pacemaker implanted. However, an appropriate risk assessment is still necessary after the implantation of a pacemaker, a change of its generator, or major modification of its programming settings.
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http://dx.doi.org/10.1016/j.shaw.2013.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791084PMC
September 2013

Predictive value of electrocardiographic T-wave morphology parameters and T-wave peak to T-wave end interval for sudden cardiac death in the general population.

Circ Arrhythm Electrophysiol 2013 Aug 23;6(4):690-6. Epub 2013 Jul 23.

Division of Cardiology, Department of Medicine, Helsinki University Central Hospital, Finland.

Background: Previous population studies have found an association between electrocardiographic T-wave morphology parameters and cardiovascular mortality, but their relationship to sudden cardiac death (SCD) is not clear. To our knowledge, there are no follow-up studies assessing the association between electrocardiographic T-wave peak to T-wave end interval (TPE) and SCD. We assessed the predictive value of electrocardiographic T-wave morphology parameters and TPE for SCD in an adult general population sample.

Methods And Results: A total of 4 T-wave morphology parameters (principal component analysis ratio, T-wave morphology dispersion, total cosine R-to-T, T-wave residuum) as well as TPE were measured from digital standard 12-lead ECGs in 5618 adults (46% men; mean age 50.9±12.5 years) participating in the Finnish population-based Health 2000 Study. After a mean follow-up time of 7.7±1.4 years, 72 SCDs had occurred. In univariable analyses, all T-wave morphology parameters were associated with an increased SCD risk. In multivariable Cox models, T-wave morphology dispersion and total cosine R-to-T remained as predictors of SCD, with T-wave morphology dispersion showing the highest SCD risk (hazard ratio of 1.4 [95% confidence interval 1.1-1.7, P=0.001] per 1 SD increase in the loge T-wave morphology dispersion). In contrast, TPE was not associated with SCD in univariable or multivariable analyses.

Conclusions: Electrocardiographic T-wave morphology parameters describing the 3-dimensional shape of the T-wave stratify SCD risk in the general population, but we did not find an association between TPE and SCD.
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http://dx.doi.org/10.1161/CIRCEP.113.000356DOI Listing
August 2013

Identification of a KCNQ1 polymorphism acting as a protective modifier against arrhythmic risk in long-QT syndrome.

Circ Cardiovasc Genet 2013 Aug 15;6(4):354-61. Epub 2013 Jul 15.

INSERM, UMR S956, Paris, France.

Background: Long-QT syndrome (LQTS) is characterized by such striking clinical heterogeneity that, even among family members carrying the same mutation, clinical outcome can range between sudden death and no symptoms. We investigated the role of genetic variants as modifiers of risk for cardiac events in patients with LQTS.

Methods And Results: In a matched case-control study including 112 patient duos with LQTS from France, Italy, and Japan, 25 polymorphisms were genotyped based on either their association with QTc duration in healthy populations or on their role in adrenergic responses. The duos were composed of 2 relatives harboring the same heterozygous KCNQ1 or KCNH2 mutation: 1 with cardiac events and 1 asymptomatic and untreated. The findings were then validated in 2 independent founder populations totaling 174 symptomatic and 162 asymptomatic patients with LQTS, and a meta-analysis was performed. The KCNQ1 rs2074238 T-allele was significantly associated with a decreased risk of symptoms 0.34 (0.19-0.61; P<0.0002) and with shorter QTc (P<0.0001) in the combined discovery and replication cohorts.

Conclusions: We provide evidence that the KCNQ1 rs2074238 polymorphism is an independent risk modifier with the minor T-allele conferring protection against cardiac events in patients with LQTS. This finding is a step toward a novel approach for risk stratification in patients with LQTS.
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http://dx.doi.org/10.1161/CIRCGENETICS.113.000023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864834PMC
August 2013

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

Circulation 2013 Jul 14;128(3):237-43. Epub 2013 Jun 14.

Population Health Research Institute, McMaster University and Hamilton Health Sciences, Hamilton,

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.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.112.001139DOI Listing
July 2013

Minimizing ventricular pacing by a novel atrioventricular (AV) delay hysteresis algorithm in patients with intact or compromised intrinsic AV conduction and different atrial and ventricular lead locations.

Ann Med 2013 Sep 14;45(5-6):438-45. Epub 2013 Jun 14.

Department of Cardiology, Helsinki University Central Hospital, Meilahti Hospital, Helsinki, Finland.

Purpose: To investigate if an advanced AV search hysteresis (AVSH) algorithm, Ventricular Intrinsic Preference (VIP(™)), reduces the incidence of ventricular pacing (VP) in sinus node dysfunction (SND) with both intact and compromised AV conduction and with intermittent AV block regardless of the lead positions in the right atria and the ventricle.

Methods: Patients were classified as having intact AV (AVi) conduction if the PR interval was ≤ 210 ms on ECG and 1:1 AV conduction during atrial pacing up to 120 bpm with PR interval ≤ 350 ms. Otherwise the AV conduction was classified as compromised (AVc). Both AVi and AVc patients were randomized to VIP ON or OFF. VIP performed an intrinsic AV conduction search every 30 s for three consecutive atrial cycles with the extension of the sensed and paced AV (SAV/PAV) delays from basic values of 150/200 ms to 300/350 ms. Extended AV intervals were allowed for three cycles when VP occurred before returning to basic AV delays. The primary end-point was %VP at 12 months.

Results: Among 389 patients, 30.1% had intact and 69.9% had compromised AV conduction. The mean %VP at 12 months was 9.6% by VIP compared to 51.8% with standard AV settings in patients with AVi (P < 0.0001) and 28.0% versus 78.9% (P < 0.0001) with AVc. With VIP, excessive %VP among most used lead positions was not seen. Conversely, when VIP was off %VP was low only in patients who had leads in the RA septal-RV septal position (23.0%).

Conclusions: VIP feature reduces VP both in patients with SND and with intermittent heart block regardless of the lead positions in the right atria and the ventricle.
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http://dx.doi.org/10.3109/07853890.2013.801710DOI Listing
September 2013

Predicting recovery of myocardial function by electrocardiography after acute infarction.

Ann Noninvasive Electrocardiol 2013 May 22;18(3):230-9. Epub 2012 Nov 22.

Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/anec.12015DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932276PMC
May 2013

Characteristics of atrial fibrillation and comorbidities in familial atrial fibrillation.

J Cardiovasc Electrophysiol 2013 Jul 29;24(7):768-74. Epub 2013 Mar 29.

Department of Cardiology, Helsinki University Central Hospital, Helsinki, Finland.

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.
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http://dx.doi.org/10.1111/jce.12127DOI Listing
July 2013

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

Europace 2013 Mar 1;15(3):388-94. Epub 2012 Nov 1.

Safe New Technologies, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250 Helsinki, Finland.

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.
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http://dx.doi.org/10.1093/europace/eus345DOI Listing
March 2013

Cell model of catecholaminergic polymorphic ventricular tachycardia reveals early and delayed afterdepolarizations.

PLoS One 2012 4;7(9):e44660. Epub 2012 Sep 4.

Institute of Biomedical Technology, University of Tampere, Tampere, Finland.

Background: Induced pluripotent stem cells (iPSC) provide means to study the pathophysiology of genetic disorders. Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a malignant inherited ion channel disorder predominantly caused by mutations in the cardiac ryanodine receptor (RyR2). In this study the cellular characteristics of CPVT are investigated and whether the electrophysiological features of this mutation can be mimicked using iPSC -derived cardiomyocytes (CM).

Methodology/principal Findings: Spontaneously beating CMs were differentiated from iPSCs derived from a CPVT patient carrying a P2328S mutation in RyR2 and from two healthy controls. Calcium (Ca(2+)) cycling and electrophysiological properties were studied by Ca(2+) imaging and patch-clamp techniques. Monophasic action potential (MAP) recordings and 24h-ECGs of CPVT-P2328S patients were analyzed for the presence of afterdepolarizations. We found defects in Ca(2+) cycling and electrophysiology in CPVT CMs, reflecting the cardiac phenotype observed in the patients. Catecholaminergic stress led to abnormal Ca(2+) signaling and induced arrhythmias in CPVT CMs. CPVT CMs also displayed reduced sarcoplasmic reticulum (SR) Ca(2+) content, indicating leakage of Ca(2+) from the SR. Patch-clamp recordings of CPVT CMs revealed both delayed afterdepolarizations (DADs) during spontaneous beating and in response to adrenaline and also early afterdepolarizations (EADs) during spontaneous beating, recapitulating the changes seen in MAP and 24h-ECG recordings of patients carrying the same mutation.

Conclusions/significance: This cell model shows aberrant Ca(2+) cycling characteristic of CPVT and in addition to DADs it displays EADs. This cell model for CPVT provides a platform to study basic pathology, to screen drugs, and to optimize drug therapy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0044660PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3433449PMC
January 2013

Stress proneness in molecularly defined long QT syndrome: a study using temperament assessment by behavioural inhibition system scale.

Stress Health 2013 Apr 30;29(2):150-5. Epub 2012 Aug 30.

IBS, Unit of Personality, Work and Health Psychology, University of Helsinki, Helsinki, Finland.

The long QT syndrome (LQTS) is an inherited cardiac disorder that predisposes the mutation carrier to ventricular arrhythmias that can lead to sudden death. The objective of the present study was to replicate the previous finding in terms of stress-related temperament trait, i.e. behavioural inhibition system (BIS). The study subjects included 583 LQTS mutation carriers (256 symptomatic and 327 asymptomatic) from the Finnish LQTS registry and 79 healthy subjects randomly derived from the population-based sample of the Young Finns Study. Symptomatic and asymptomatic LQTS mutation carriers did not differ from each other on BIS (3.27 versus 3.24, p > 0.05), whereas LQTS mutation carriers scored higher on BIS than the comparison group derived from the representative population-based sample (3.25 versus 2.99, p = 0.003, η² = 0.014). BIS was significantly higher in women than in men (3.32 versus 3.06, p < 0.001, η² = 0.017). The results confirm our previous finding of higher stress proneness of LQTS mutation carriers. Their innate stress proneness may have relevance because it increases our understanding on the role of stress in the manifestation of symptoms.
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http://dx.doi.org/10.1002/smi.2441DOI Listing
April 2013

Microwave Ablation in Mitral Valve Surgery for Atrial Fibrillation (MAMA).

J Atr Fibrillation 2012 Aug-Sep;5(2):432. Epub 2012 Aug 20.

Department of Cardiology, Linnköping University Hospital, Linnköping, Sweden.

Microwave ablation in conjunction with open heart surgery is effective in restoring sinus rhythm (SR) in patients with atrial fibrillation (AF). In patients assigned for isolated mitral valve surgery no prospective randomized trial has reported its efficacy. 70 patients with longlasting AF where included from 5 different centres. They were randomly assigned to mitral valve surgery and atrial microwave ablation or mitral valve surgery alone. Out of 70 randomized, 66 and 64 patients were available for evaluation at 6 and 12 months. At 12 months SR was restored and preserved in 71.0 % in the ablation group vs 36.4 % in the control group (P=0.006), corresponding figures at 6 months was 62.5 % vs 26.5 % (P=0.003). The 30-day mortality rate was 1.4 %, with one death in the ablation group vs zero deaths in the control group. At 12 months the mortality rate was 7,1 % (Ablation n=3 vs Control n=2). No significant differences existed between the groups with regard to the overall rate of serious adverse events (SAE) during the perioperative period or at the end of the study. 16 % of patients randomized to ablation were on antiarrhytmic drugs compared to 6 % in the control group after 1 year (p=0.22). Microwave ablation of left and right atrium in conjunction with mitral valve surgery is safe and effectively restores sinus rhythm in patients with longlasting AF as compared to mitral valve surgery alone.
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http://dx.doi.org/10.4022/jafib.432DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5153116PMC
August 2012

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

Scand Cardiovasc J 2012 Oct 21;46(5):308-14. Epub 2012 Aug 21.

Safe New Technologies, Finnish Institute of Occupational Health, Helsinki, Finland.

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.
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http://dx.doi.org/10.3109/14017431.2012.716525DOI Listing
October 2012

Performance of atrial tachyarrhythmia-sensing algorithms in dual-chamber pacing using a fixed long AV delay in patients with sinus node dysfunction.

J Interv Card Electrophysiol 2012 Nov 12;35(2):207-13. Epub 2012 Jun 12.

Department of Cardiology, Meilahti Hospital, Helsinki University Central Hospital, Haartmaninkatu 4, P.O. Box 340, 00029 HUS, Helsinki, Finland.

Aims: The aim of the study was to evaluate the performance of pacemakers (PM) atrial tachyarrhythmia (AT)-sensing algorithms in sinus node dysfunction (SND) patients with DDDR pacing programmed with a fixed long atrioventricular (AV) delay.

Methods: In a prospective study, a total of 60 patients with SND were implanted with a dual-chamber PM with two different algorithms for detection of ATs. The study was done with a 3 month data collection period retrieved from the memory of PM and with a 7 day external Holter recording period.

Results: In 13 of 16 (81 %) patients whose Holter recording revealed the presence of ATs, episodes of AT sensing were retrieved from the PM memory with electrograms verifications, confirming that the devices had detected the ATs. Very short ATs seen in Holter recordings were missed by the PM with three patients. However, with all these patients after 3 months of follow up period, there were recognized periods of ATs by the PM. With ten (17 %) patients, there were intermittent periods of undersensing by the PM although continuous atrial fibrillation (AF) was seen in the Holter recording. Retrograde conduction caused false AT detection due to repetitive non-reentrant ventriculoatrial synchronous rhythm (RNRVAS) in six (25 %) of the 24 patients with retrograde conduction.

Conclusions: Even with long AV delay, ATs can be accurately identified. However, transient undersensing of continuous AF and non-detection of very short AT episodes can still occur. Programming a long AV delay predisposes to RNRVAS which can cause false AT detection and symptoms in SND patients who have retrograde conduction.
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http://dx.doi.org/10.1007/s10840-012-9691-4DOI Listing
November 2012

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

J Electrocardiol 2012 Jul-Aug;45(4):368-372. Epub 2012 May 4.

Helsinki University Central Hospital, Department of Cardiology, Helsinki, Finland.

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.
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http://dx.doi.org/10.1016/j.jelectrocard.2012.04.007DOI Listing
November 2012

A common variant near the KCNJ2 gene is associated with T-peak to T-end interval.

Heart Rhythm 2012 Jul 15;9(7):1099-103. Epub 2012 Feb 15.

Research Program in Molecular Medicine, University of Helsinki, Helsinki, Finland.

Background: T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown.

Objective: To identify common genetic variants that affect the duration of the TPE interval in the general population.

Methods: We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V(2), and V(5) on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study.

Results: We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes.

Conclusion: The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.
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http://dx.doi.org/10.1016/j.hrthm.2012.02.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3690340PMC
July 2012

Experimental study on malfunction of pacemakers due to exposure to different external magnetic fields.

J Interv Card Electrophysiol 2012 Jun 11;34(1):19-27. Epub 2012 Jan 11.

Safe New Technologies, Finnish Institute of Occupational Health, Topeliuksenkatu 41 a A, 00250, Helsinki, Finland.

Purpose: Cardiac pacemaker malfunction due to exposure to magnetic fields may cause serious problems in some work environments for workers having cardiac pacemakers. The aim of this study was to find the magnetic field interference thresholds for several commonly used pacemaker models.

Methods: We investigated 16 pacemakers from three different manufacturers with the frequency range of 2 to 1,000 Hz, using sinusoidal, pulse, ramp, and square waveforms. The magnetic fields were produced by a computer-controlled Helmholtz coil system.

Results: Pacemaker malfunction occurred in six of 16 pacemakers. Interaction developed almost immediately after high-intensity magnetic field exposure started. With each waveform, at least two pacemakers exhibited interference. In most exposure settings, there was no interference at magnetic field levels below the international occupational safety limits. Nevertheless, some frequencies using ramp or square waveforms interfered with pacemakers even at levels below public exposure limits. The occurrence of interference depended greatly on the waveform, frequency, magnetic field intensity, and the sensing configuration of the pacemaker. Unipolar configurations were more susceptible for interference than the bipolar ones. In addition, magnetic fields perpendicular to the pacemaker loops were more likely to cause interference than parallel fields.

Conclusion: There is a need for further investigations on pacemaker interference caused by different external magnetic fields to ensure safe working environment to workers with a pacemaker.
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http://dx.doi.org/10.1007/s10840-011-9651-4DOI Listing
June 2012
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