Umeå University's logo

Background: Data on long-term effects of catheter ablation vs antiarrhythmic drugs (AADs) on health-related quality of life (HRQoL) and atrial fibrillation (AF) burden are limited.

Objective: The study aimed to assess long-term HRQoL and rhythm data in patients with symptomatic AF.

Methods: The 75 patients who underwent ablation and 74 receiving AADs in the Catheter Ablation compared with Pharmacological Therapy for Atrial Fibrillation (CAPTAF) trial were followed for 48 months. The General Health subscale of the 36-Item Short-Form Health Survey, time to first AF episode ≥1 hour, and AF burden, recorded by implantable cardiac monitors, were compared.

Results: One hundred forty-seven patients completed follow-up, with 7 crossovers in the ablation group and 34 crossovers in the AAD group. General Health improved by ablation from a median of 62 points at baseline to 79.2 points at follow-up (P < .001) and by AADfrom a median of 67 to 77 points (P < .001), without treatment differences (P = .77). Time to first AF episode ≥1 hour was longer (median 257 days in the ablation group vs 180 days in the AAD group; P = .025). The cumulative AF burden during follow-up was lower in the ablation group (median 0.3%; interquartile range [IQR] 0%–1.4%) than in the AAD group (1.6%; IQR 0.1%–11.0%); P = .01. The cumulative reduction in AF burden compared with baseline was greater in the ablation group (median −89.5%; IQR −98.4% to −51.3%) than in the AAD group (−52.7%; IQR −92.6% to 263.6%); P < .001.

Conclusion: HRQoL improvement in long-term did not differ between ablation and AAD groups despite a larger reduction in AF burden after ablation. The results should be interpreted in the light of a high crossover rate in the AAD group.

Hysteresis, a ubiquitous regulatory phenomenon, is a salient feature of the adaptation of ventricular repolarization duration to heart rate (HR) change. We therefore compared the QT interval adaptation to rapid HR increase in patients with the long QT syndrome type 1 (LQT1) versus healthy controls because LQT1 is caused by loss-of-function mutations affecting the repolarizing potassium channel current IKs , presumably an important player in QT hysteresis. The study was performed in an outpatient hospital setting. HR was increased in LQT1 patients and controls by administering an intravenous bolus of atropine (0.04 mg/kg body weight) for 30 s. RR and QT intervals were recorded by continuous Frank vectorcardiography. Atropine induced transient expected side effects but no adverse arrhythmias. There was no difference in HR response (RR intervals) to atropine between the groups. Although atropine-induced ΔQT was 48% greater in 18 LQT1 patients than in 28 controls (p < 0.001), QT adaptation was on average 25% faster in LQT1 patients (measured as the time constant τ for the mono-exponential function and the time for 90% of ΔQT; p < 0.01); however, there was some overlap between the groups, possibly a beta-blocker effect. The shorter QT adaptation time to atropine-induced HR increase in LQT1 patients on the group level corroborates the importance of IKs in QT adaptation hysteresis in humans and shows that LQT1 patients have a disturbed ultra-rapid cardiac memory. On the individual level, the QT adaptation time possibly reflects the effect-size of the loss-of-function mutation, but its clinical implications need to be shown.

The use of implantable cardioverter defibrillators (ICDs) in long QT syndrome (LQTS) patients is essential in high-risk patients. However, it is sometimes used in patients without high-risk profiles for whom the expected benefit may be lower than the risk of ICD harm. Here, we evaluated ICD benefit and harm by assessing risk according to risk scores and pre-ICD clinical characteristics. Design. We studied 109 Swedish LQTS patients drawn from the Swedish ICD and Pacemaker Registry with data collected from medical records. In addition to clinical characteristics, we used two risk scores to assess pre-ICD risk, and evaluated ICD benefit and harm. Results. Twenty percent of all patients received ≥1 appropriate shock with a first appropriate shock incidence rate of 4.3 per 100 person-years. A long QTc (≥550 ms) and double mutations were significantly associated with appropriate shock. Low risk scores among patients without pre-ICD aborted cardiac arrest were not significantly associated with low risk of first appropriate shock. The incidence rates of a first inappropriate shock and first complication were 3.0 and 7.6 per 100 person-years, respectively. Conclusion. Our findings on ICD harm emphasize the importance of careful individual pre-ICD consideration. When we applied two risk scores to patients without pre-ICD aborted cardiac arrest, we could not validate their ability to identify patients with low risk of appropriate shocks and patients who were assessed as having a low risk still received appropriate shocks. This further supports the complexity of risk stratification and the difficulty of using risk scores.

BACKGROUND: Although myocardial infarction (MI) and atrial fibrillation (AF) are frequent comorbidities and share common cardiovascular risk factors, the direction and strength of the association of the risk factors with disease onset, subsequent disease incidence, and mortality are not completely understood.

METHODS AND RESULTS: In pooled multivariable Cox regression analyses, we examined temporal relations of disease onset and identified predictors of MI, AF, and all-cause mortality in 108 363 individuals (median age, 46.0 years; 48.2% men) free of MI and AF at baseline from 6 European population-based cohorts. During a maximum follow-up of 10.0 years, 3558 (3.3%) individuals were diagnosed exclusively with MI, 1922 (1.8%) with AF but no MI, and 491 (0.5%) individuals developed both MI and AF. Association of sex, systolic blood pressure, antihypertensive treatment, and diabetes appeared to be stronger with incident MI than with AF, whereas increasing age and body mass index showed a higher risk for incident AF. Total cholesterol and daily smoking were significantly related to incident MI but not AF. Combined population attributable fraction of cardiovascular risk factors was >70% for incident MI, whereas it was only 27% for AF. Subsequent MI after AF (hazard ratio [HR], 1.68; 95% CI, 1.03–2.74) and subsequent AF after MI (HR, 1.75; 95% CI, 1.31–2.34) both significantly increased overall mortality risk.

CONCLUSIONS: We observed different associations of cardiovascular risk factors with both diseases indicating distinct pathophysiological pathways. Subsequent diagnoses of MI and AF significantly increased mortality risk.

BACKGROUND: There are conflicting reports with regard to the allele-specific gene suppression effects of single nucleotide polymorphisms (SNPs) in the 3’untranslated region (3’UTR) of the KCNQ1 gene in long QT syndrome type 1 (LQT1) populations. Here we assess the allele-specific effects of 3 previously published 3’UTR-KCNQ1’s SNPs in a LQT1 founder population segregating a dominant-negative mutation.

METHODS AND RESULTS: Bidirectional sequencing of the KCNQ1’s 3’UTR was performed in the p.Y111C founder population (n=232, 147 genotype positive), with a minor allele frequency of 0.1 for SNP1 (rs2519184) and 0.6 for linked SNP2 (rs8234) and SNP3 (rs107980). Allelic phase was assessed in trios aided by haplotype data, revealing a high prevalence of derived SNP2/3 in cis with p.Y111C (89%). Allele-specific association analyses, corrected using a relatedness matrix, were performed between 3’UTR-KCNQ1 SNP genotypes and clinical phenotypes. SNP1 in trans was associated with a significantly higher proportion of symptomatic phenotype compared with no derived SNP1 allele in trans (58% versus 32%, corrected P=0.027). SNP2/3 in cis was associated with a significantly lower proportion of symptomatic phenotype compared with no derived SNP2/3 allele in cis (32% versus 69%, corrected P=0.010).

CONCLUSIONS: Allele-specific modifying effects on symptomatic phenotype of 3’UTR-KCNQ1 SNPs rs2519184, rs8234, and rs107980 were seen in a LQT1 founder population segregating a dominant-negative mutation. The high prevalence of sup-pressive 3’UTR-KCNQ1 SNPs segregating with the founder mutation could contribute to the previously documented low incidence of cardiac events in heterozygous carriers of the p.Y111C KCNQ1 mutation.

Objectives: It is well-established that the autonomic nervous system (ANS) plays a central role in arrhythmogenesis. During and after exercise the ANS is particularly active, and since long QT syndrome (LQTS) patients have an increased risk of lethal arrhythmias during physical activity, it is important to investigate the autonomic function in these patients. In this study we investigate the ANS response during and after exercise in LQTS patients and healthy age and sex matched controls.

Methods: Forty-four genotype-verified adult LQTS patients and forty-four healthy age- and sex-matched controls performed a submaximal bicycle exercise stress test. Heart rate recovery (HRR) and heart rate variability (HRV) were analyzed from registered electrocardiogram (ECG) and vector electrocardiogram (VCG) recordings collected throughout rest, exercise and in the post-exercise phase.

Results: LQTS patients had a slower HRR than controls at 1- and 4-min post-exercise (p < 0.001). During the post-exercise phase, LQTS patients had a lower total power (p < 0.001), low frequency power (p < 0.001) and high frequency power (p < 0.001) than controls. In the same phase, LQTS patients off betablocker (BB) treatment showed a lower high frequency power (p = 0.01) and different low frequency/high frequency ratio (p = 0.003) when comparing with LQTS patients on BB treatment.

Conclusions: The parasympathetic effect on both HRR and HRV after exercise appears depressed in this LQTS patient cohort compared to healthy controls. This indicates an aberrant ANS response during the post-exercise phase which might be compensated by BB treatment. Our findings emphasize the importance of performing further investigations to identify the role of the ANS in LQTS arrhythmogenesis.

AIMS: There is inconsistent evidence on the relation of alcohol intake with incident atrial fibrillation (AF), in particular at lower doses. We assessed the association between alcohol consumption, biomarkers, and incident AF across the spectrum of alcohol intake in European cohorts.

METHODS AND RESULTS: In a community-based pooled cohort, we followed 107 845 individuals for the association between alcohol consumption, including types of alcohol and drinking patterns, and incident AF. We collected information on classical cardiovascular risk factors and incident heart failure (HF) and measured the biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin I. The median age of individuals was 47.8 years, 48.3% were men. The median alcohol consumption was 3 g/day. N = 5854 individuals developed AF (median follow-up time: 13.9 years). In a sex- and cohort-stratified Cox regression analysis alcohol consumption was non-linearly and positively associated with incident AF. The hazard ratio for one drink (12 g) per day was 1.16, 95% CI 1.11-1.22, P < 0.001. Associations were similar across types of alcohol. In contrast, alcohol consumption at lower doses was associated with reduced risk of incident HF. The association between alcohol consumption and incident AF was neither fully explained by cardiac biomarker concentrations nor by the occurrence of HF.

CONCLUSIONS: In contrast to other cardiovascular diseases such as HF, even modest habitual alcohol intake of 1.2 drinks/day was associated with an increased risk of AF, which needs to be considered in AF prevention.

Aims: To assess the relation between atrial fibrillation (AF) characteristics and health-related quality of life (QoL), and which AF characteristic had the greatest impact.

Method: The AF characteristics burden (percentage of time in AF), duration and number of AF episodes/month were obtained from implantable cardiac monitors during the 2-month run-in period in 150 patients included in the randomized CAPTAF trial comparing early ablation and antiarrhythmic drug therapy. The QoL was measured by the General Health and Vitality dimensions of the 36-Item Short-Form Health Survey. AF characteristics were analysed continuously and in quartiles (Q1-Q4).

Results: Greater AF burden (p = 0.003) and longer AF episodes (p = 0.013) were associated with impaired QoL (Vitality score only) in simple linear regression analyses. Greater AF burden was, however, the only AF characteristic associated with lower QoL, when adjusted for sex, type of AF, hypertension, heart rate above 110 beats per minute during AF, and beta-blocker use in multiple linear regression analyses. For every 10% increase in AF burden there was a 1.34-point decrease of Vitality score (95% confidence interval (CI) −2.67 to −0.02, p = 0.047). The Vitality score was 12 points lower (95% CI −22.73 to −1.27, p = 0.03) in patients with an AF burden > 33% (Q4) versus those with < 0.45% (Q1), but only in unadjusted analysis.

Conclusion: AF burden had a greater impact on QoL (Vitality), than the duration and number of AF episodes, corroborating that AF burden may be the preferred outcome measure of rhythm control in trials including relatively healthy AF populations.

Aims: To assess whether the prevailing rhythm at the time of replying to symptom and health-related quality of life (HR-QoL) questionnaires impacts the findings.

Method: A total of 150 patients from the randomized Catheter Ablation Compared with Pharmacological Therapy for Atrial Fibrillation-trial, comparing atrial fibrillation (AF) ablation versus drugs, were included. The effect of the prevailing rhythm on the outcome results of the HR-QoL 36-Item Short-Form Health Survey, the symptom severity questionnaire (SSQ), and the European Heart Rhythm Association (EHRA) score for classification of AF-related symptoms was assessed.

Results: AF as the prevailing rhythm was independently associated with a significantly lower Vitality score; 18.4 points lower (95% confidence interval -32.7 to -4.1, p = .01) compared with sinus rhythm when adjusted for AF burden, median duration of episode, number of episodes, beta-blocker use, type of AF, and sex. The presence of AF did not affect the General Health score compared with sinus rhythm, nor did it influence symptoms assessed by the SSQ or EHRA score.

Conclusion: The observation that the presence of AF versus sinus rhythm when conducting HR-QoL tests had a negative impact on its outcome, leaving symptom-related questionnaires unaffected, implies that the prevailing rhythm should be taken into account when results of HR-QoL questionnaires are interpreted.

Comprehensive genetic and clinical care of families with monogenic cardiovascular diseases requires competences from different medical specialties. Genetic assessment, cascade screening, risk estimation, treatment and follow-up is difficult to cover. Fourteen years ago, a center for cardiovascular diseases was created in our hospital, to improve the care of families with monogenic cardiovascular diseases. At our center, clinical geneticists, cardiologists, angiologists, pediatric cardiologists and genetic counselors work together in a seamless organization, while still having different clinic affiliations. A key feature of this organization are the family outpatient clinics, where the proband and his/her relatives at genetic risk are invited to take part. When the family or relatives live in other parts of the country, they are invited to participate through video conference.  In this paper we report our experiences and working routines from more than 300 families and 2000 individuals.