Mitral annular disjunction in idiopathic ventricular fibrillation patients: just a bystander or a potential cause?

AIMS: Previously, we demonstrated that inferolateral mitral annular disjunction (MAD) is more prevalent in patients with idiopathic ventricular fibrillation (IVF) than in healthy controls. In the present study, we advanced the insights into the prevalence and ventricular arrhythmogenicity by inferolateral MAD in an even larger IVF cohort. METHODS AND RESULTS: This retrospective multi-centre study included 185 IVF patients [median age 39 (27, 52) years, 40% female]. Cardiac magnetic resonance images were analyzed for mitral valve and annular abnormalities and late gadolinium enhancement. Clinical characteristics were compared between patients with and without MAD. MAD in any of the 4 locations was present in 112 (61%) IVF patients and inferolateral MAD was identified in 24 (13%) IVF patients. Mitral valve prolapse (MVP) was found in 13 (7%) IVF patients. MVP was more prevalent in patients with inferolateral MAD compared with patients without inferolateral MAD (42 vs. 2%, P < 0.001). Pro-arrhythmic characteristics in terms of a high burden of premature ventricular complexes (PVCs) and non-sustained ventricular tachycardia (VT) were more prevalent in patients with inferolateral MAD compared to patients without inferolateral MAD (67 vs. 23%, P < 0.001 and 63 vs. 41%, P = 0.046, respectively). Appropriate implantable cardioverter defibrillator therapy during follow-up was comparable for IVF patients with or without inferolateral MAD (13 vs. 18%, P = 0.579). CONCLUSION: A high prevalence of inferolateral MAD and MVP is a consistent finding in this large IVF cohort. The presence of inferolateral MAD is associated with a higher PVC burden and non-sustained VTs. Further research is needed to explain this potential interplay.

Prevalence of anxiety and risk associated with ventricular arrhythmia in patients with an implantable cardioverter defibrillator.

BACKGROUND: Anxiety has been associated with adverse clinical outcomes in patients who have received an implantable cardioverter defibrillator (ICD). However, results are inconclusive likely due to different measures being used to assess anxiety. Hence, the current study aims to examine the prevalence and the association between anxiety, ventricular tachyarrhythmia's (VTa's) and all-cause mortality, respectively. METHODS: Patients who received an ICD for the first time were recruited from 6 Dutch referral hospitals as part of the WEBCARE trial. Patients filled in validated questionnaires (GAD-7, STAI-S, HADS-A, ANX4, ICDC, FSAS) to assess their baseline anxiety symptomatology. Logistic regression analysis and Cox Regression analysis were performed to examine the association between anxiety with 1) VTa's and 2) mortality, respectively. RESULTS: A total of 214 Patients were included in the analysis with mean age 58.9 and 82.7% being male. The prevalence rates of anxiety varied depending on which questionnaire was used 12.4% (GAD-7), 17.5% (HADS-A), and 28.1% (STAI-S). (Cox) Regression analysis revealed that none of the anxiety measures was associated with VTa's or all-cause mortality in the current sample. Stratifying the sample by gender, the analysis showed that GAD-7, STAI-S, and ANX4 scores were associated with increased risk of VTa's but only in male patients. CONCLUSIONS: Prevalence rates of anxiety varied depending on the measurement tool used. No significant association between anxiety and VTa's and all-cause mortality was observed in the total sample. GAD-7, STAI-S, and ANX4 were associated with increased risk for VTa's but only in male patients.

Personality traits, ventricular tachyarrhythmias, and mortality in patients with an implantable cardioverter defibrillator: 6 years follow-up of the WEBCARE cohort.

OBJECTIVE: Risk stratification within the ICD population warrants the examining of the role of protective- and risk factors. Current study examines the association between Type D personality, pessimism, and optimism and risk of ventricular tachyarrhythmias (VTa's) and mortality in patients with a first-time ICD 6 years post implantation. METHODS: A total of 221 first-implant ICD patients completed questionnaires on optimism and pessimism (Life Orientation Test) and Type D personality (Type D scale DS14) 10 to 14 days after implantation. VTa's and all-cause mortality 6 years post implant comprised the study endpoints. RESULTS: Ninety (40.7%) patients had experienced VTa's and 37 (16.7%) patients died, 12 (5.4%) due to a cardiac cause. Adjusted logistic regression analysis showed that pessimism was significantly associated with increased risk of VTa's (OR = 1.09; 95% CI = 1.00-1.19; p = .05). Type D personality (OR = 1.05; 95% CI = 0.47-2.32; p = .91) and optimism (OR = 1.00; 95% CI = 0.90-1.12; p = .98) were not associated with VTa's. None of the personality types were associated with mortality. CONCLUSION: Pessimism was associated with VTa's but not with mortality. No significant association with either of the endpoints was observed for Type D personality and optimism. Future research should focus on the coexistent psychosocial factors that possibly lead to adverse cardiac prognosis in this patient population.

Appropriate use criteria for optical coherence tomography guidance in percutaneous coronary interventions : Recommendations of the working group of interventional cardiology of the Netherlands Society of Cardiology.

INTRODUCTION: Optical coherence tomography (OCT) enables detailed imaging of the coronary wall, lumen and intracoronary implanted devices. Responding to the lack of specific appropriate use criteria (AUC) for this technique, we conducted a literature review and a procedure for appropriate use criteria. METHODS: Twenty-one of all 184 members of the Dutch Working Group on Interventional Cardiology agreed to evaluate 49 pre-specified cases. During a meeting, factual indications were established whereupon members individually rated indications on a 9-point scale, with the opportunity to substantiate their scoring. RESULTS: Twenty-six indications were rated 'Appropriate', eighteen indications 'May be appropriate', and five 'Rarely appropriate'. Use of OCT was unanimously considered 'Appropriate' in stent thrombosis, and 'Appropriate' for guidance in PCI, especially in distal left main coronary artery and proximal left anterior descending coronary artery, unexplained angiographic abnormalities, and use of bioresorbable vascular scaffold (BVS). OCT was considered 'Rarely Appropriate' on top of fractional flow reserve (FFR) for treatment indication, assessment of strut coverage, bypass anastomoses or assessment of proximal left main coronary artery. CONCLUSIONS: The use of OCT in stent thrombosis is unanimously considered 'Appropriate' by these experts. Varying degrees of consensus exists on the appropriate use of OCT in other settings.

Anemia predicts thromboembolic events, bleeding complications and mortality in patients with atrial fibrillation: insights from the RE-LY trial.

BACKGROUND: Anemia may predispose to thromboembolic events or bleeding in anticoagulated patients with atrial fibrillation (AF). OBJECTIVES: To investigate whether anemia is associated with thromboembolic events and bleeding in patients with AF. PATIENTS AND METHODS: We retrospectively analyzed the RE-LY trial database, which randomized 18 113 patients with AF and a risk of stroke to receive dabigatran or warfarin for a median follow-up of 2 years. Cox regression analysis was used to determine whether anemia predicted cardiovascular events and bleeding complications in these patients. RESULTS: Anemia was present in 12% of the population at baseline, and the presence of anemia was associated with a higher risk of thromboembolic cardiovascular events, including the composite endpoint of all-cause mortality or myocardial infarction (adjusted hazard ratio [HR] 1.50, 95% confidence interval [CI] 1.32-1.71) and the primary RE-LY outcome of stroke or systemic embolism (adjusted HR 1.41, 95% CI 1.12-1.78). Anemia was also associated with a higher risk of major bleeding complications (adjusted HR 2.14, 95% CI 1.87-2.46) and discontinuation of anticoagulants (adjusted HR 1.40, 95% CI 1.28-1.79). The association between anemia and outcome was similar irrespective of cardiovascular comorbidities, randomized treatment allocation, or prior use of warfarin. The incidence of events was lower in patients with transient anemia than in patients in whom anemia was sustained (adjusted HR 0.66, 95% CI 0.49-0.91). CONCLUSIONS: Anemia is associated with an increased risk of thromboembolic events, bleeding complications and mortality in anticoagulated patients with AF. These findings suggest that patients with anemia should be monitored closely during all types of anticoagulant treatment.

Loss of consciousness and convulsion induced by a ventricular tachycardia mimicking epilepsy in a patient with noncompaction cardiomyopathy: a case report.

Convulsions and loss of consciousness can be caused by, among other things, arrhythmias, conduction disorders or epilepsy. In clinical practice it can be difficult to distinguish between these causes of syncope, even for well-trained specialists. Patients with cardiac syncope have a substantial risk of subsequent sudden death. We present a patient with previously unknown noncompaction cardiomyopathy in whom syncope induced by ventricular tachycardia was misinterpreted as epilepsy. We present this case report in order to underline the necessity for cardiological assessment in patients with assumed mild epilepsy or syncope of unknown origin.

Routine versus aggressive upstream rhythm control for prevention of early atrial fibrillation in heart failure: background, aims and design of the RACE 3 study.

BACKGROUND: Rhythm control for atrial fibrillation (AF) is cumbersome because of its progressive nature caused by structural remodelling. Upstream therapy refers to therapeutic interventions aiming to modify the atrial substrate, leading to prevention of AF. OBJECTIVE: The Routine versus Aggressive upstream rhythm Control for prevention of Early AF in heart failure (RACE 3) study hypothesises that aggressive upstream rhythm control increases persistence of sinus rhythm compared with conventional rhythm control in patients with early AF and mild-to-moderate early systolic or diastolic heart failure undergoing electrical cardioversion. DESIGN: RACE 3 is a prospective, randomised, open, multinational, multicenter trial. Upstream rhythm control consists of angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers, mineralocorticoid receptor antagonists, statins, cardiac rehabilitation therapy, and intensive counselling on dietary restrictions, exercise maintenance, and drug adherence. Conventional rhythm control consists of routine rhythm control therapy without cardiac rehabilitation therapy and intensive counselling. In both arms, every effort is made to keep patients in the rhythm control strategy, and ion channel antiarrhythmic drugs or pulmonary vein ablation may be instituted if AF relapses. Total inclusion will be 250 patients. If upstream therapy proves to be effective in improving maintenance of sinus rhythm, it could become a new approach to rhythm control supporting conventional pharmacological and non-pharmacological rhythm control.

Attachment site selection of ticks on roe deer, Capreolus capreolus.

The spatio-temporal attachment site patterns of ticks feeding on their hosts can be of significance if co-feeding transmission (i.e. from tick to tick without a systemic infection of the host) of pathogens affects the persistence of a given disease. Using tick infestation data on roe deer, we analysed preferred attachment sites and niche width of Ixodes ticks (larvae, nymphs, males, females) and investigated the degree of inter- and intrastadial aggregation. The different development stages showed rather consistent attachment site patterns and relative narrow feeding site niches. Larvae were mostly found on the head and on the front legs of roe deer, nymphs reached highest densities on the head and highest adult densities were found on the neck of roe deer. The tick stages feeding (larvae, nymphs, females) on roe deer showed high degrees of intrastadial spatial aggregation, whereas males did not. Male ticks showed large feeding site overlap with female ticks. Feeding site overlap between larval-female and larval-nymphal ticks did occur especially during the months May-August on the head and front legs of roe deer and might allow pathogen transmission via co-feeding. Tick density, niche width and niche overlap on roe deer are mainly affected by seasonality, reflecting seasonal activity and abundance patterns of ticks. Since different tick development stages occur spatially and temporally clustered on roe deer, transmission experiments of tick-borne pathogens are urgently needed.

Body-mass or sex-biased tick parasitism in roe deer (Capreolus capreolus)? A GAMLSS approach.

Macroparasites feeding on wildlife hosts follow skewed distributions for which basic statistical approaches are of limited use. To predict Ixodes spp. tick burden on roe deer, we applied Generalized Additive Models for Location, Scale and Shape (GAMLSS) which allow incorporating a variable dispersion. We analysed tick burden of 78 roe deer, sampled in a forest region of Germany over a period of 20 months. Assuming a negative binomial error distribution and controlling for ambient temperature, we analysed whether host sex and body mass affected individual tick burdens. Models for larval and nymphal tick burden included host sex, with male hosts being more heavily infested than female ones. However, the influence of host sex on immature tick burden was associated with wide standard errors (nymphs) or the factor was marginally significant (larvae). Adult tick burden was positively correlated with host body mass. Thus, controlled for host body mass and ambient temperature, there is weak support for sex-biased parasitism in this system. Compared with models which assume linear relationships, GAMLSS provided a better fit. Adding a variable dispersion term improved only one of the four models. Yet, the potential of modelling dispersion as a function of variables appears promising for larger datasets.

Acute success and short-term follow-up of catheter ablation of isthmus-dependent atrial flutter; a comparison of 8 mm tip radiofrequency and cryothermy catheters.

OBJECTIVES: To compare the acute success and short-term follow-up of ablation of atrial flutter using 8 mm tip radiofrequency (RF) and cryocatheters. METHODS: Sixty-two patients with atrial flutter were randomized to RF or cryocatheter (cryo) ablation. Right atrial angiography was performed to assess the isthmus. End point was bidirectional isthmus block on multiple criteria. A pain score was used and the analgesics were recorded. Patients were followed for at least 3 months. RESULTS: The acute success rate for RF was 83% vs 69% for cryo (NS). Procedure times were similar (mean 144+/-48 min for RF, vs 158+/-49 min for cryo). More applications were given with RF than with cryo (26+/-17 vs. 18+/-10, p<0.05). Fluoroscopy time was longer with RF (29+/-15 vs. 19+/-12 min, p<0.02). Peak CK, CK-MB and CK-MB mass were higher, also after 24 h in the cryo group. Troponin T did not differ. Repeated transient block during application (usually with cryoablation) seemed to predict failure. Cryothermy required significantly less analgesia (p<0.01), and no use of long sheaths (p<0.005). The isthmus tended to be longer in the failed procedures (p=0.117). This was similar for both groups, as was the distribution of anatomic variations. Recurrences and complaints in the successful patients were similar for both groups, with a very low recurrence of atrial flutter after initial success. CONCLUSIONS: In this randomized study there was no statistical difference but a trend to less favorable outcome with 8 mm tip cryocatheters compared to RF catheters for atrial flutter ablation. Cryoablation was associated with less discomfort, fewer applications, shorter fluoroscopy times and similar procedure times. The recurrence rate was very low. Cryotherapy can be considered for atrial flutter ablation under certain circumstances especially when it has been used previously in the same patient, such as in an AF ablation.

Tachycardiomyopathy with familial predisposition masquerading as peripartum cardiomyopathy.

A 28-year-old pregnant lady presented with cardiomyopathy and atrial tachycardia. The patient had severe heart failure and syncope. Her past medical history was uneventful. Her mother, however, had received an implantable cardioverter defibrillator (ICD) after an out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation. The patient was scheduled for programmed stimulation, during which a monomorphic ventricular tachycardia was induced. An ICD was then implanted. Following radiofrequency ablation of the atrial tachycardia, left ventricular function recovered completely. Given the family history, a genetic predisposition to both arrhythmias and tachycardiomyopathy needs to be considered.

Quinidine induced electrocardiographic normalization in two patients with Brugada syndrome.

Two patients with Brugada syndrome are presented. The ECGs showed right precordial J waves and ST-segment elevation. Patient 1 was resuscitated from nocturnal ventricular fibrillation, patient 2 was asymptomatic. In only patient 1, flecainide was infused causing monomorphic "malignant" ventricular extrasystoles (R on T), demonstrating the deleterious effect of Class IC antiarrhythmic drugs in Brugada syndrome. However, administration of the Class Ia antiarrhythmic drug quinidine caused normalization of the ECG in both patients. Based on in vitro experiments, agents that reduce the magnitude of Ito-mediated phase 1 have been suggested to normalize ST-segment elevation in Brugada syndrome. This is the first clinical report of such a quinidine induced ECG normalization.

Congenital long-QT syndrome caused by a novel mutation in a conserved acidic domain of the cardiac Na+ channel.

BACKGROUND: Congenital long-QT syndrome (LQTS) is an inherited condition of abnormal cardiac excitability characterized clinically by an increased risk of ventricular tachyarrhythmias. One form, LQT3, is caused by mutations in the cardiac voltage-dependent sodium channel gene, SCN5A. Only 5 SCN5A mutations have been associated with LQTS, and more work is needed to improve correlations between SCN5A genotypes and associated clinical syndromes. METHODS AND RESULTS: We researched a 3-generation white family with autosomal dominant LQTS who exhibited a wide clinical spectrum from mild bradycardia to sudden death. Molecular genetic studies revealed a single nucleotide substitution in SCN5A exon 28 that caused the substitution of Glu1784 by Lys (E1784K). The mutation occurs in a highly conserved domain within the C-terminus of the cardiac sodium channel containing multiple, negatively charged amino acids. Two-electrode voltage-clamp recordings of a recombinant E1784K mutant channel expressed in Xenopus oocytes revealed a defect in fast inactivation characterized by a small, persistent current during long membrane depolarizations. Coexpression of the mutant with the human sodium channel beta1-subunit did not affect the persistent current, even though we did observe shifts in the voltage dependence of steady-state inactivation. Neutralizing multiple, negatively charged residues in the same region of the sodium channel C-terminus did not cause a more severe functional defect. CONCLUSIONS: We characterized the genetics and molecular pathophysiology of a novel SCN5A sodium channel mutation, E1784K. The functional defect exhibited by the mutant channel causes delayed myocardial repolarization, and our data on the effects of multiple charge neutralizations in this region of the C-terminus suggest that the molecular mechanism of channel dysfunction involves an allosteric rather than a direct effect on channel gating.

Long-term (subacute) potassium treatment in congenital HERG-related long QT syndrome (LQTS2).

INTRODUCTION: Congenital long QT syndrome (LQTS) is subdivided according to the underlying gene defect. In LQTS2, an aberrant HERG gene that encodes the potassium channel IKr leads to insufficient IKr activity and delayed repolarization, causing ECG abnormalities and torsades de pointes (TdP). Increasing serum potassium levels by potassium infusion normalizes the ECG in LQTS2 because IKr activity varies with serum potassium levels. METHODS AND RESULTS: In an LQTS2 patient who presented with TdP, we attempted to achieve a long-term (subacute) elevation of serum potassium by increased potassium intake and potassium-sparing drugs. However, due to renal potassium homeostasis, it was impossible to achieve a long-lasting rise of serum potassium above 4.0 mmol/L. CONCLUSION: Although raising serum potassium reverses the ECG abnormalities in LQTS2, a long-lasting rise of serum potassium is only partially achievable because in the presence of normal renal function, potassium homeostasis limits the amount of serum potassium increase.