Search

Aims Papillary muscle (PM) abnormalities are considered part of the phenotypic spectrum of hypertrophic cardiomyopathy (HCM). The aim of this study was to evaluate the presence and frequency of PM displacement in different HCM phenotypes. Methods and results We retrospectively analysed cardiovascular magnetic resonance (CMR) findings in 156 patients (25% females, median age 57 years). Patients were divided into three groups: septal hypertrophy (Sep-HCM, n = 70, 45%), mixed hypertrophy (Mixed-HCM, n = 48, 31%), and apical hypertrophy (Ap-HCM, n = 38, 24%). Fifty-five healthy subjects were enrolled as controls. Apical PM displacement was observed in 13% of controls and 55% of patients, which was most common in the Ap-HCM group, followed by the Mixed-HCM and Sep-HCM groups (respectively: inferomedial PM 92 vs. 65 vs. 13%, P < 0.001; anterolateral PM 61 vs. 40 vs. 9%, P < 0.001). Significant differences in PM displacement were found when comparing healthy controls with patients with Ap- and Mixed-HCM subtypes but not when comparing them with patients with the Sep-HCM subtype. T-wave inversion in the inferior and lateral leads was more frequent in patients with Ap-HCM (100 and 65%, respectively) when compared with Mixed-HCM (89 and 29%, respectively) and Sep-HCM (57 and 17%, respectively; P < 0.001 for both). Eight patients with Ap-HCM had prior CMR examinations because of T-wave inversion [median interval 7 (3–8) years], and in the first CMR study, none showed apical hypertrophy [median apical wall thickness 8 (7–9) mm], while all of them presented with apical PM displacement. Conclusion Apical PM displacement is part of the phenotypic Ap-HCM spectrum and may precede the development of hypertrophy. These observations suggest a potential pathogenetic, mechanical link between apical PM displacement and Ap-HCM. [ABSTRACT FROM AUTHOR]

Aims The impact of long-term endurance sport participation (on top of a healthy lifestyle) on coronary atherosclerosis and acute cardiac events remains controversial. Methods and results The Master@Heart study is a well-balanced prospective observational cohort study. Overall, 191 lifelong master endurance athletes, 191 late-onset athletes (endurance sports initiation after 30 years of age), and 176 healthy non-athletes, all male with a low cardiovascular risk profile, were included. Peak oxygen uptake quantified fitness. The primary endpoint was the prevalence of coronary plaques (calcified, mixed, and non-calcified) on computed tomography coronary angiography. Analyses were corrected for multiple cardiovascular risk factors. The median age was 55 (50–60) years in all groups. Lifelong and late-onset athletes had higher peak oxygen uptake than non-athletes [159 (143–177) vs. 155 (138–169) vs. 122 (108–138) % predicted]. Lifelong endurance sports was associated with having ≥1 coronary plaque [odds ratio (OR) 1.86, 95% confidence interval (CI) 1.17–2.94], ≥ 1 proximal plaque (OR 1.96, 95% CI 1.24–3.11), ≥ 1 calcified plaques (OR 1.58, 95% CI 1.01–2.49), ≥ 1 calcified proximal plaque (OR 2.07, 95% CI 1.28–3.35), ≥ 1 non-calcified plaque (OR 1.95, 95% CI 1.12–3.40), ≥ 1 non-calcified proximal plaque (OR 2.80, 95% CI 1.39–5.65), and ≥1 mixed plaque (OR 1.78, 95% CI 1.06–2.99) as compared to a healthy non-athletic lifestyle. Conclusion Lifelong endurance sport participation is not associated with a more favourable coronary plaque composition compared to a healthy lifestyle. Lifelong endurance athletes had more coronary plaques, including more non-calcified plaques in proximal segments, than fit and healthy individuals with a similarly low cardiovascular risk profile. Longitudinal research is needed to reconcile these findings with the risk of cardiovascular events at the higher end of the endurance exercise spectrum. [ABSTRACT FROM AUTHOR]

Aims Fragmented QRS complex with visible notching on standard 12-lead electrocardiogram (ECG) is understood to represent depolarization abnormalities and to signify risk of cardiac events. Depolarization abnormalities with similar prognostic implications likely exist beyond visual recognition but no technology is presently suitable for quantification of such invisible ECG abnormalities. We present such a technology. Methods and results A signal processing method projects all ECG leads of the QRS complex into optimized three perpendicular dimensions, reconstructs the ECG back from this three-dimensional projection, and quantifies the difference (QRS 'micro'-fragmentation, QRS- μf) between the original and reconstructed signals. QRS 'micro'-fragmentation was assessed in three different populations: cardiac patients with automatic implantable cardioverter-defibrillators, cardiac patients with severe abnormalities, and general public. The predictive value of QRS- μf for mortality was investigated both univariably and in multivariable comparisons with other risk factors including visible QRS 'macro'-fragmentation, QRS- Mf. The analysis was made in a total of 7779 subjects of whom 504 have not survived the first 5 years of follow-up. In all three populations, QRS- μf was strongly predictive of survival (P < 0.001 univariably, and P < 0.001 to P = 0.024 in multivariable regression analyses). A similar strong association with outcome was found when dichotomizing QRS- μf prospectively at 3.5%. When QRS- μf was used in multivariable analyses, QRS- Mf and QRS duration lost their predictive value. Conclusion In three populations with different clinical characteristics, QRS- μf was a powerful mortality risk factor independent of several previously established risk indices. Electrophysiologic abnormalities that contribute to increased QRS- μf values are likely responsible for the predictive power of visible QRS- Mf. [ABSTRACT FROM AUTHOR]

Aims Cardiac output limitation is a fundamental feature of heart failure with preserved ejection fraction (HFpEF) but the relative contribution of its determinants in symptomatic vs. asymptomatic stages are not well characterized. We aimed to gain insight into disease mechanisms by performing comprehensive comparative non-invasive exercise imaging in patients across the disease spectrum. Methods and results We performed bicycle stress echocardiography in 10 healthy controls, 13 patients with hypertensive left ventricular (LV) concentric remodelling and asymptomatic diastolic dysfunction (HTDD), 15 HFpEF patients, and 15 subjects with isolated right ventricular (RV) dysfunction secondary to chronic thromboembolic pulmonary hypertension (CTEPH). During exercise, ventricular performance differed across the groups (all P ≤ 0.01 for interaction). Notably in controls, LV and RV function significantly increased (all P < 0.05) while both LV systolic and diastolic reserve were significantly reduced in HFpEF patients. Likewise, RV systolic reserve was also impaired in HFpEF but not to the extent of CTEPH patients (P < 0.001 between groups). HTDD patients behaved as an intermediary group with borderline LV systolic and diastolic reserve and reduced RV systolic reserve. The increased pulmonary vascular (PV) load in HFpEF and CTEPH patients in combination with impaired RV reserve resulted in RV–pulmonary artery uncoupling during exercise. Conclusion The multifaceted decline of cardiac and PV function accompanying disease progression in HFpEF is unmasked by exercise and already emerges in preclinical disease. The revelation of these subtle abnormalities during exercise illustrates the benefit of exercise imaging and creates new prospects for early diagnosis and management. [ABSTRACT FROM AUTHOR]

Aim: The association of standard 12-lead electrocardiogram (ECG) markers with benefits of the primary prophylactic implantable cardioverter-defibrillator (ICD) has not been determined in the contemporary era. We analysed traditional and novel ECG variables in a large prospective, controlled primary prophylactic ICD population to assess the predictive value of ECG in terms of ICD benefit.Methods and Results: Electrocardiograms from 1477 ICD patients and 700 control patients (EU-CERT-ICD; non-randomized, controlled, prospective multicentre study; ClinicalTrials.gov Identifier: NCT02064192), who met ICD implantation criteria but did not receive the device, were analysed. The primary outcome was all-cause mortality. In ICD patients, the co-primary outcome of first appropriate shock was used. Mean follow-up time was 2.4 ± 1.1 years to death and 2.3 ± 1.2 years to the first appropriate shock. Pathological Q waves were associated with decreased mortality in ICD patients [hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.35-0.84; P < 0.01] and patients with pathological Q waves had significantly more benefit from ICD (HR 0.44, 95% CI 0.21-0.93; P = 0.03). QTc interval increase taken as a continuous variable was associated with both mortality and appropriate shock incidence, but commonly used cut-off values, were not statistically significantly associated with either of the outcomes.Conclusion: Pathological Q waves were a strong ECG predictor of ICD benefit in primary prophylactic ICD patients. Excess mortality among Q wave patients seems to be due to arrhythmic death which can be prevented by ICD. [ABSTRACT FROM AUTHOR]

Aims Mitral valve prolapse (MVP) causes left ventricular (LV) remodelling even in the absence of significant mitral regurgitation. To evaluate whether apical insertion of the papillary muscle (PM) influences the pattern and severity of MVP-related LV remodelling. Methods and results All MVP patients who underwent CMR at our institution between December 2008 and December 2019 were included, thoroughly reviewed and grouped according to apical/non-apical PM insertion. Apical PM insertion was found in 53/92 patients (58%) and associated with mitral leaflet thickening (P  < 0.01) and a trend towards higher prevalence of mitral annular disjunction (P  = 0.05). Whereas no differences in ventricular volumes or ejection fraction were found, patients with apical PM insertion showed more lateral wall remodelling with mid lateral wall thinning [2.1 (1.8–2.5) vs. 4.0 (3.5–5.0) mm, P  < 0.01], increased LV eccentricity and a lower GCS at this level (15 ± 3% vs. 20 ± 3%, P  < 0.01). In long-axis direction, increased end-diastolic mid lateral wall angulation was found (i.e. angle <155° measured in the thinnest point of the mid lateral wall in four-chamber view) with a higher angle variation during systole (25 ± 11° vs. 17 ± 8°, P  < 0.01). Remarkably, PM fibrosis was significantly more frequent in patients with apical PM insertion (i.e. 66% vs. 28%, P  < 0.01). Finally, a higher burden of premature ventricular complexes (>5%) and non-sustained ventricular tachyarrhythmias was found in patients with apical PM insertion: 53% vs. 25% (P  = 0.04) and 38% vs. 18% (P  = 0.04), respectively. Conclusion Apical PM insertion is part of the phenotypic spectrum of MVP, impacts significantly LV remodelling, and potentially may be related to increased ventricular arrhythmogenicity. [ABSTRACT FROM AUTHOR]

Aims: We identified the first Belgian SCN5A founder mutation, c.4813 + 3_4813 + 6dupGGGT. To describe the clinical spectrum and disease severity associated with this mutation, clinical data of 101 SCN5A founder mutation carriers and 46 non-mutation carrying family members from 25 Belgian families were collected.Methods and Results: The SCN5A founder mutation was confirmed by haplotype analysis. The clinical history and electrocardiographic parameters of the mutation carriers and their family members were gathered and compared. A cardiac electrical abnormality was observed in the majority (82%) of the mutation carriers. Cardiac conduction defects, defined as PR or QRS prolongation on electrocardiogram (ECG), were most frequent, occurring in 65% of the mutation carriers. Brugada syndrome (BrS) was the second most prevalent phenotype identified in 52%, followed by atrial dysrythmia in 11%. Overall, 33% of tested mutation carriers had a normal sodium channel blocker test. Negative tests were more common in family members distantly related to the proband. Overall, 23% of the mutation carriers were symptomatic, with 8% displaying major adverse events. As many as 13% of the patients tested with a sodium blocker developed ventricular arrhythmia. One family member who did not carry the founder mutation was diagnosed with BrS.Conclusion: The high prevalence of symptoms and sensitivity to sodium channel blockers in our founder population highlights the adverse effect of the founder mutation on cardiac conduction. The large phenotypical heterogeneity, variable penetrance, and even non-segregation suggest that other genetic (and environmental) factors modify the disease expression, severity, and outcome in these families. [ABSTRACT FROM AUTHOR]

Aims The EUropean Comparative Effectiveness Research to Assess the Use of Primary ProphylacTic Implantable Cardioverter-Defibrillators (EU-CERT-ICD), a prospective investigator-initiated, controlled cohort study, was conducted in 44 centres and 15 European countries. It aimed to assess current clinical effectiveness of primary prevention ICD therapy. Methods and results We recruited 2327 patients with ischaemic cardiomyopathy (ICM) or dilated cardiomyopathy (DCM) and guideline indications for prophylactic ICD implantation. Primary endpoint was all-cause mortality. Clinical characteristics, medications, resting, and 12-lead Holter electrocardiograms (ECGs) were documented at enrolment baseline. Baseline and follow-up (FU) data from 2247 patients were analysable, 1516 patients before first ICD implantation (ICD group) and 731 patients without ICD serving as controls. Multivariable models and propensity scoring for adjustment were used to compare the two groups for mortality. During mean FU of 2.4 ± 1.1 years, 342 deaths occurred (6.3%/years annualized mortality, 5.6%/years in the ICD group vs. 9.2%/years in controls), favouring ICD treatment [unadjusted hazard ratio (HR) 0.682, 95% confidence interval (CI) 0.537–0.865, P  = 0.0016]. Multivariable mortality predictors included age, left ventricular ejection fraction (LVEF), New York Heart Association class

Background Atrioventricular nodal reentrant tachycardia (AVNRT) is a common supraventricular arrhythmia that is frequently encountered in an otherwise healthy patient population. Recent guidelines of the European Society of Cardiology underline the role of catheter ablation in the long-term management of these patients. Case summary This case describes the clinical presentation and treatment options in a patient with typical slow/fast AVNRT, the most common subform of AVNRT, where antegrade conduction occurs over the slow pathway and retrograde conduction over the fast pathway. The ablation strategy in these patients is illustrated based on intracardiac recordings in combination with per-procedural three-dimensional imaging. Discussion Atrioventricular nodal reentrant tachycardia is a common arrhythmia with good prognosis but significant impact on quality of life of affected patients. Catheter ablation should be considered early as it can be performed safely and with a very high success rate. [ABSTRACT FROM AUTHOR]

Aims Athletes with right ventricular (RV) arrhythmias, even in the absence of desmosomal mutations, may have subtle RV abnormalities which can be unmasked by deformation imaging. As exercise places a disproportionate stress on the right ventricle, evaluation of cardiac function and deformation during exercise might improve diagnostic performance. Methods and results We performed bicycle stress echocardiography in 17 apparently healthy endurance athletes (EAs), 12 non-athletic controls (NAs), and 17 athletes with RV arrhythmias without desmosomal mutations (EI-ARVCs) and compared biventricular function at rest and during low (25% of upright peak power) and moderate intensity (60%). At rest, we observed no differences in left ventricular (LV) or RV function between groups. During exercise, however, the increase in RV fractional area change (RVFAC), RV free wall strain (RVFWSL), and strain rate (RVFWSRL) were significantly attenuated in EI-ARVCs as compared to EAs and NAs. At moderate exercise intensity, EI-ARVCs had a lower RVFAC, RVFWSL, and RVFWSRL (all P  < 0.01) compared to the control groups. Exercise-related increases in LV ejection fraction, strain, and strain rate were also attenuated in EI-ARVCs (P  < 0.05 for interaction). Exercise but not resting parameters identified EI-ARVCs and RVFWSRL with a cut-off value of >−2.35 at moderate exercise intensity had the greatest accuracy to detect EI-ARVCs (area under the curve 0.95). Conclusion Exercise deformation imaging holds promise as a non-invasive diagnostic tool to identify intrinsic RV dysfunction concealed at rest. Strain rate appears to be the most accurate parameter and should be incorporated in future, prospective studies to identify subclinical disease in an early stage. [ABSTRACT FROM AUTHOR]

Aims: Prolonged participation in exercise results in structural and electrical cardiac remodelling. The development of an athlete's heart is recognized as a risk factor for atrial arrhythmias. This study aims to evaluate the impact of athlete heart remodelling on the presentation of atrioventricular nodal re-entrant tachycardia (AVNRT).Methods and Results: A retrospective analysis of an ablation database selecting all patients with an electrophysiologically confirmed diagnosis of AVNRT. Athletes (individuals participating in moderate to intensive sports for ≥3 h per week having done so for ≥5 years) were compared with healthy non-athletes. Atrioventricular nodal re-entrant tachycardia subforms were classified according the methods described by Katritsis and Josephson in 2013 and by Heidbuchel and Jackman in 2014. A total of 504 AVNRT patients were fully characterized, of whom 85 (17%) were athletes. Almost half of the athletes presented with atypical forms of AVNRT, where in non-athletes this frequency was about 20%. There was no difference in acute procedural success among the two groups, but the procedures in athletes were more complex, as reflected by an almost two-fold increase in the use of a long sheath to reach the slow pathway ablation area and a higher recurrence rate in athletes (10% vs. 4%).Conclusion: Athletes present more frequently with atypical subforms of AVNRT. This is possibly related to cardiac remodelling with dilatation of the cardiac cavities leading to changed conduction properties in the septal area. Ablation outcome is equally safe in athletes as in non-athletes with similar acute success rates. Athletes experience a higher longer-term recurrence rate. [ABSTRACT FROM AUTHOR]

Aims Observation of better outcome in women after cardiac resynchronization therapy (CRT) has led to controversies about a potential sex-specific response. In this study, we investigated to which extent this sex-specific difference in CRT outcome could be explained by differences in baseline characteristics between both sexes. Methods and results We retrospectively analysed data from a multicentre registry of 1058 patients who received CRT. Patients were examined by echocardiography before and 12 ± 6 months after implantation. Response was defined as ≥15% reduction of left ventricular end-systolic volume at follow-up. Patient's characteristics at baseline, including New York Heart Association class, ejection fraction, QRS width and morphology, ischaemic aetiology of cardiomyopathy (ICM), number of scarred segments, age at implantation, atrial fibrillation, and mechanical dyssynchrony (Dyss) were analysed. Patients were followed for a median duration of 59 months. Primary end point was all-cause mortality. Women (24% of the population) had less ICM (23% vs. 49%, P  <   0.0001), less scarred segments (0.4 ± 1.3 vs. 1.0 ± 2.1, P  <   0.0001), more left bundle branch block (LBBB; 87% vs. 80%, P  =   0.01), and more Dyss at baseline (78% vs. 57%, P  <   0.0001). Without matching baseline differences, women showed better survival (log rank P  <   0.0001). After matching, survival was similar (log rank P  =   0.58). In multivariable analysis, female sex was no independent predictor of neither volumetric response (P  =   0.06) nor survival (P  =   0.31). Conclusion Our data suggest that the repeatedly observed better outcome in women after CRT is mainly due to the lower rate ICM and smaller scars. When comparing patients with similar baseline characteristics, the response of both sexes to CRT is similar. [ABSTRACT FROM AUTHOR]

Aim To determine if incorporation of assessment of mechanical dyssynchrony could improve the prognostic value of patient selection based on current guidelines. Methods and results Echocardiography was performed in 1060 patients before and 12 ± 6 months after cardiac resynchronization therapy (CRT) implantation. Mechanical dyssynchrony, defined as the presence of apical rocking or septal flash was visually assessed at the baseline examination. Response was defined as ≥15% reduction in left ventricular end-systolic volume at follow-up. Patients were followed for a median of 59 months (interquartile range 37–86 months) for the occurrence of death of any cause. Applying the latest European guidelines retrospectively, 63.4% of the patients had been implanted with a Class I recommendation, 18.2% with Class IIa, 9.4% with Class IIb, and in 9% no clear therapy recommendation was present. Response rates were 65% in Class I, 50% in IIa, 38% in IIb patients, and 40% in patients without a clear guideline-based recommendation. Assessment of mechanical dyssynchrony improved response rates to 77% in Class I, 75% in IIa, 62% in IIb, and 69% in patients without a guideline-based recommendation. Non-significant difference in survival among guideline recommendation classes was found (Log-rank P  = 0.2). Presence of mechanical dyssynchrony predicted long-term outcome better than guideline Classes I, IIa, IIb (Log-rank P  <   0.0001, 0.006, 0.004, respectively) and in patients with no guideline recommendation (P  = 0.02). Comparable results were observed using the latest American Guidelines. Conclusion Our data suggest that current guideline criteria for CRT candidate selection could be improved by incorporating assessment of mechanical asynchrony. [ABSTRACT FROM AUTHOR]

Aims: Therapy with an implantable cardioverter defibrillator (ICD) is established for the prevention of sudden cardiac death (SCD) in high risk patients. We aimed to determine the effectiveness of primary prevention ICD therapy by analysing registry data from 14 centres in 11 European countries compiled between 2002 and 2014, with emphasis on outcomes in women who have been underrepresented in all trials.Methods and results: Retrospective data of 14 local registries of primary prevention ICD implantations between 2002 and 2014 were compiled in a central database. Predefined primary outcome measures were overall mortality and first appropriate and first inappropriate shocks. A multivariable model enforcing a common hazard ratio for sex category across the centres, but allowing for centre-specific baseline hazards and centre specific effects of other covariates, was adjusted for age, the presence of ischaemic cardiomyopathy or a CRT-D, and left ventricular ejection fraction ≤25%. Of the 5033 patients, 957 (19%) were women. During a median follow-up of 33 months (IQR 16-55 months) 129 women (13%) and 807 men (20%) died (HR 0.65; 95% CI: [0.53, 0.79], P-value < 0.0001). An appropriate ICD shock occurred in 66 women (8%) and 514 men (14%; HR 0.61; 95% CI: 0.47-0.79; P = 0.0002).Conclusion: Our retrospective analysis of 14 local registries in 11 European countries demonstrates that fewer women than men undergo ICD implantation for primary prevention. After multivariate adjustment, women have a significantly lower mortality and receive fewer appropriate ICD shocks. [ABSTRACT FROM AUTHOR]

Aims: The latest 2015 ESC Guidelines on the prevention of sudden cardiac death make a Class IIa recommendation for ICD implantation in patients listed for heart transplantation. This recommendation was based on expert consensus in view of the sparsity of data.Methods and results: All patients listed for heart transplantation at the University Hospitals of Leuven from 2002 until 2014 were studied retrospectively. Exclusion criteria were age <16 years, cardiac disease other than ischaemic or dilated cardiomyopathy and re-transplantation. A total of 286 patients were included, of which 140 (49.0%) received an ICD. There was a historical increase of the time on the waiting list before transplantation (P < 0.001) together with an increase of the use of ICDs (P < 0.001) and left ventricular assist devices (LVADs) (P < 0.001). The proportion of patients reaching heart transplant remained unchanged (P = 0.700). The annual appropriate shock rate in patients with ICD was 28.0%/y on the active waiting list. Patients with ICD showed a trend to improved survival (P = 0.070). Independent predictors of mortality or removal from the transplant list because of clinical deterioration were the need for LVAD (HR 4.38, 95%CI 2.11-9.01), a history of stroke (HR 2.95, 95%CI 1.61-5.40), older age (HR 1.03, 95%CI 1.01-1.05) and a worse renal function (HR 1.15, 95%CI 1.00-1.33).Conclusion: The time on the waiting list for heart transplantation significantly increased together with an increased use of device therapy in this population. The proportion of patients reaching transplant remained unchanged. This patient group is prone to life-threatening arrhythmias and the use of an ICD may improve survival. [ABSTRACT FROM AUTHOR]

Aims: Clinical experience indicates that limited or no reverse left ventricular (LV) remodelling may not necessarily imply non-response to cardiac resynchronization therapy (CRT). We investigated the association of the extent of LV remodelling, mechanical dyssynchrony, and survival in patients undergoing CRT. Methods and results: In 356 CRT candidates, three blinded readers visually assessed the presence of mechanical dyssynchrony (either apical rocking and/or septal flash) before device implantation and also its correction by CRT 12 ± 3 months post-implantation. To assess LV reverse remodelling, end-systolic volumes (ESV) were measured at the same time points. Patients were divided into four subgroups: no LV remodelling (ESV change 0 ± 5%), mild LV reverse remodelling (ESV reduction 5-15%), significant LV reverse remodelling (ESV reduction ≥ 5%), and LV volume expansion (ESV increase ≥5%). Patients were followed for all-cause mortality during the median follow-up of 36 months. Patients with LV remodelling as in the above defined groups showed 58, 54, and 84% reduction in all-cause mortality compared to patients with volume expansion. In multivariable analysis, LVESV change remained independently associated with survival, with an 8% reduction in mortality for every 10% decrease in LVESV (P = 0.0039), but an optimal cut-off point could not be established. In comparison, patients with corrected mechanical dyssynchrony showed 71% reduction in all-cause mortality (P < 0.001). Conclusion: Volumetric response assessed at 1-year after CRT is strongly associated with long-term mortality. However, an optimal cut-off cannot be established. The association of the correction of mechanical dyssynchrony with survival was stronger than that of any volumetric cut-off. [ABSTRACT FROM AUTHOR]

Aims: Accumulation of atrial adipose tissue is associated with atrial fibrillation (AF). However, the underlying mechanisms remain poorly understood. We examined the relationship between the characteristics of fatty infiltrates of the atrial myocardium and the history of AF. Methods and results: Atrial samples, collected in 92 patients during cardiac surgery and in a sheep model of persistent AF, were subjected to a detailed histological analysis. In sections of human right atrial samples, subepicardial fatty infiltrations were commonly observed in the majority of patients. A clear difference in the appearance and fibrotic content of these fatty infiltrations was observed. Fibro-fatty infiltrates predominated in patients with permanent AF (no AF: 37 ± 24% vs. paroxysmal AF: 50 ± 21% vs. permanent AF: 64 ± 23%, P < 0.001). An inverse correlation between fibrotic remodelling and the amount of subepicardial adipose tissue suggested the progressive fibrosis of fatty infiltrates with permanent AF. This hypothesis was tested in a sheep model of AF. In AF sheep, an increased accumulation of peri-atrial fat depot was observed on cardiac magnetic resonance imaging and dense fibro-fatty infiltrations predominated in the left atria of AF sheep. Cellular inflammation, mainly consisting of functional cytotoxic T lymphocytes, was observed together with adipocyte cell death in human atria. Conclusion: Atrial fibrillation is associated with the fibrosis of subepicardial fatty infiltrates, a process in which cytotoxic lymphocytes might be involved. This remodelling of the atrial subepicardium could contribute to structural remodelling forming a substrate for AF. [ABSTRACT FROM AUTHOR]

AIMS: Apical rocking (ApRock) and septal flash (SF) are often observed phenomena in asynchronously contracting ventricles. We investigated the relationship of visually assessed ApRock and SF, reverse remodelling, and long-term survival in cardiac resynchronization therapy (CRT) candidates. METHODS AND RESULTS: A total of 1060 patients eligible for CRT underwent echocardiographic examinations before and 12 ± 6 months after device implantation. Three blinded physicians were asked to visually assess the presence of ApRock and SF before device implantation and also their correction by CRT 12 ± 6 months post-implantation. Patients with a left ventricular (LV) end-systolic volume decrease of ≥15% during the first year of follow-up were regarded as responders. Patients were followed for a median period of 46 months (interquartile range: 27-65 months) for the occurrence of death of any cause. If corrected by CRT, visually assessed ApRock and SF were associated with reverse remodelling with a sensitivity of 84 and 79%, specificity of 79 and 74%, and accuracy of 82 and 77%, respectively. ApRock (hazard ratio [HR] 0.40, 95% confidence interval [CI] 0.30-0.53, P < 0.0001) and SF (HR 0.45 [CI 0.34-0.61], P < 0.001) were independently associated with lower all-cause mortality after CRT and had an incremental value over clinical variables and QRS width for identifying CRT responders. Both the absence of ApRock/SF and unsuccessful correction of ApRock/SF despite CRT were associated with a high risk for non-response and an unfavourable long-term survival. CONCLUSION: A specific LV mechanical dyssynchrony pattern, characterized by ApRock and SF, is associated with a more favourable long-term survival after CRT. Both parameters are also indicators of an effective therapy. [ABSTRACT FROM AUTHOR]

Aims: In atrial fibrillation (AF), abnormalities in Ca2+ release contribute to arrhythmia generation and contractile dysfunction. We explore whether RyR cluster ultrastructure is altered and is associated with functional abnormalities in AF. Methods and Results: Using high resolution confocal microscopy (STED) we examined RyR cluster morphology in fixed atrial myocytes from sheep with persistent AF (N=6) and control (Ctrl; N=6) animals. RyR clusters on average contained 15 contiguous RyRs; this did not differ between AF and Ctrl. However, the distance between clusters was significantly reduced in AF (288±12 nm vs. 376±17 nm). When RyR clusters were grouped into Ca2+ release units (CRUs), i.e. clusters separated by <150 nm), CRUs in AF had more clusters (3.43±0.10 vs. 2.95±0.02 in Ctrl), which were more dispersed. Furthermore, in AF cells, more RyR clusters were found between Z lines. In parallel experiments, Ca2+ sparks were monitored in live permeabilized myocytes. In AF, myocytes had: (i) >50% higher spark frequency with (ii) increased spark time-to-peak (TTP) and duration and (iii) a higher incidence of macrosparks. A computational model of the CRU was used to simulate the morphological alterations observed in AF cells. Increasing cluster fragmentation to the level observed in AF cells caused the observed changes i.e. higher spark frequency, increased TTP and duration; RyR clusters dispersed between Z-lines increased the occurrence of macrosparks. Conclusion: In persistent AF, ultrastructural reorganization of RyR clusters within CRUs is associated with overactive Ca2+ release, increasing the likelihood of propagating Ca2+ release. [ABSTRACT FROM AUTHOR]

Aims Contradicting reports have been published regarding the relation between a dobutamine-induced increase in either cardiac dyssynchrony or left-ventricular ejection fraction (LVEF) and the response to cardiac resynchronization therapy (CRT). Using apical rocking (ApRock) as surrogate dyssynchrony parameter, we investigated the dobutamine stress echocardiography (DSE)-induced changes in left-ventricular (LV) dyssynchrony and LVEF and their potential pathophysiological interdependence. Methods and results Fifty-eight guideline-selected CRT candidates were prospectively enrolled for low-dose DSE. Dyssynchrony was quantified by the amplitude of ApRock. An LVEF increase during stress of >5% was regarded significant. Scar burden was assessed by magnetic resonance imaging. Mean follow-up after CRT implantation was 41 ± 13 months for the occurrence of cardiac death. ApRock during DSE predicted CRT response (AUC 0.88, 95% CI 0.77–0.99, P < 0.001) and correlated inversely with changes in EF (r = −0.6, P < 0.001). Left-ventricular ejection fraction changes during DSE were not associated with CRT response (P = 0.082). Linear regression analysis revealed an inverse association of LVEF changes during DSE with both, total scar burden (B = −2.67, 95CI −3.77 to −1.56, P < 0.001) and the DSE-induced change in ApRock amplitude (B = −1.23, 95% CI −1.53 to −0.94, P < 0.001). Kaplan–Meier analysis revealed that DSE-induced increase in ApRock, but not LVEF, was associated with improved long-term survival. Conclusion During low-dose DSE in CRT candidates with baseline dyssynchrony, myocardial contractile reserve predominantly results in more dyssynchrony, but less in an increase in LVEF. Dyssynchrony at baseline and its dobutamine-induced changes are predictive of both response and long-term survival following CRT. [ABSTRACT FROM PUBLISHER]

The article presents the discussion on the role of sudden cardiac death to mortality for clinical effectiveness of primary prevention implantable cardioverter-defibrillator (ICDs) including distinguishing patients with increased or decreased proportion of arrhythmic death to total mortality.

Aims Oxidative stress can modulate nitric oxide (NO) signalling pathways. Both pathways have been shown to be involved in the pathophysiology of atrial fibrillation (AF), but data are conflicting. We aimed to characterize the NO-pathway and its relation to oxidative stress in persistent AF in a sheep model. Methods and results Persistent AF was induced by rapid atrial pacing for a mean of 136.5 ± 21.7 days. Non-stimulated sheep served as controls. Nicotine adenine dinucleotide phosphate (NADPH) oxidase-stimulated superoxide production was significantly increased in the AF group (+51.3 ± 23.2%, P < 0.01). Although there were no changes in mRNA expression of the different NADPH oxidase subunits, the increased activity was associated with markedly increased protein expression of the NADPH oxidase activator, Rac1 (+26 ± 4.6%, P < 0.05). No differences were seen in superoxide dismutase activity, but glutathione peroxidase activity was lower in the AF group. There was a marked accumulation of 3-nitrotyrosine, a biomarker for peroxynitrite, in atrial tissue of AF animals, as demonstrated by immunohistochemical staining and dot blot analysis (+15.6 ± 1.8%, P < 0.05). Expression of atrial NOS3 mRNA was 24.9 ± 4.4% lower in the AF group vs. control (P < 0.05), while NOS1 and 2 were unchanged. Immunoblot analysis revealed no changes in protein expression. Nitrite/nitrate levels were significantly lower during AF (−24.8 ± 5.8%, P < 0.05). Conclusion In a sheep model of persistent AF, NOS3 transcript levels are attenuated and circulating NOx levels decreased. Persistent AF is associated with increased oxidative stress, probably resulting from increased NADPH oxidase activity, without major changes in anti-oxidant capacity of the atrial tissue. [ABSTRACT FROM PUBLISHER]

Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca2+, Na+, K+) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. [ABSTRACT FROM PUBLISHER]

Aims Endurance sports activities have been associated with the development of atrial fibrillation (AF). Pulmonary vein isolation (PVI) by means of radiofrequency catheter ablation has been established as an effective treatment for AF. The aim of the present study was to analyse the efficacy of AF ablation in athletes. Methods and results We compared procedural outcome and median term follow-up in 94 consecutive athletes (>3 h of sports/week for ≥10 years or ≥1500 h lifetime) who underwent PVI (94% men, 51 ± 8 years, 87% paroxysmal AF, left atrial (LA) diameter 40 ± 8 mm, mean follow-up 41 months), and 41 contemporary controls. Sixty-three per cent of athletes performed endurance sports (running, cycling, swimming, and rowing). Documented focal induction of AF and failed treatment with ≥1 anti-arrhythmic drug were pre-requisites for selection of ablation treatment. Patients with long-standing persistent or permanent AF or an LA diameter ≥55 mm were not considered for ablation. Median lifetime cumulative hours of sports was 8638 (4175–13 688) in athletes vs. 450 (280–600) in controls (P < 0.001). Other baseline characteristics except for gender (94 vs. 66% men, respectively, P < 0.001) were comparable between both groups, as was the total number of ablation procedures per patient (1.2±0.5, P = 0.62). Survival analysis showed similar AF recurrence rate after a first ablation for controls and endurance athletes, though non-endurance athletes had a significantly higher AF recurrence rate (48 vs. 46 vs. 34% freedom from AF at 3 year follow-up after a single ablation, P= 0.04). Final outcome after all ablations was similar (87 vs. 84 vs. 85% freedom from AF at 3-year follow-up, P = 0.88). No other independent predictor for AF recurrence was identified. Conclusion In patients with documented focal induction of non-permanent AF and absence of structural heart disease, PVI is as effective in endurance athletes as in other patients. [ABSTRACT FROM PUBLISHER]

Aims Rapid atrial pacing for 1 week leads to decreased expression of endocardial nitric oxide (NO)-synthase and decreased NO concentrations. We hypothesized that increasing NO bioavailability may reduce electrical remodelling induced by atrial tachycardia. Methods and results We examined the effect of molsidomine, a NO donor, and Nω-nitro-l-arginine methylester (l-NAME), a NO-synthase inhibitor, on electrical remodelling occurring during 4 h of rapid atrial pacing in sheep. Haemodynamic and electrophysiological parameters were measured at baseline, 1 h after the start of the infusion and before the start of pacing, and 2 and 4 h after pacing. We measured the effect of molsidomine on atrial monophasic action potentials (MAPs) in non-instrumented sheep and on l-type Ca2+ currents and intracellular Ca2+ concentration ([Ca2+]i) transients in right atrial cells, isolated from control sheep. In control sheep, rapid atrial pacing shortened the atrial effective refractory period (AERP) by 12 ± 0.18% after 4 h, an effect that was unaffected by l-NAME. Infusion of molsidomine increased AERP at baseline (+13.4 ± 1.04%) and transiently attenuated pacing-induced AERP shortening (13.6 ± 0.1% at 2 h). Molsidomine tended to increase MAP duration by 20.7 ± 13.4 ms. Incubation of isolated atrial myocytes with NO donor 3-morpholino-sydnonimine (SIN-1) increased significantly l-type Ca2+ current and [Ca2+]i transients. Conclusion Infusion of molsidomine, a NO donor, delayed shortening of the action potential during short-term rapid atrial pacing, by increasing [Ca2+]i. Whereas the former could be protective against repetitive short episodes of atrial fibrillation, the latter might be detrimental in the long term. [ABSTRACT FROM PUBLISHER]

Aims Current attempts of improving patient selection in cardiac resynchronization therapy (CRT) are mainly based on echocardiographic timing of myocardial velocity peaks. Regional myocardial function is neglected. Apical transverse motion (ATM) is a new parameter to quantify apical rocking as an integrative surrogate of both temporal and functional inhomogeneities within the left ventricle. In this study, we tested the predictive value of apical rocking for response to CRT. Methods and results Sixty-nine patients eligible for CRT were assessed by echocardiography before and 11 ± 5 months after pacemaker implantation. Response was defined as left ventricular (LV) end-systolic volume decrease >15%. Rocking was quantified (ATM) and visually assessed by four blinded readers. Predictive value for CRT response of both assessments was compared with conventional dyssynchrony parameters. ATM in the four-chamber view plane differentiated best between responders and non-responders (2.2 ± 1.5 vs. 0.06 ± 1.9 mm, P< 0.0001). Quantified ATM predicted reverse remodelling with a sensitivity, specificity, and accuracy of 75, 96, and 83% whereas visual rocking assessment resulted in 89, 75, and 83%, respectively. The accuracy of conventional parameters was significantly lower. Conclusion Apical rocking is a new marker to assess LV dyssynchrony and predict CRT response. It is superior to conventional parameters. Even its simple visual assessment may be sufficiently accurate in the clinical setting. [ABSTRACT FROM AUTHOR]

Aims: Three-dimensional rotational angiography (3DRA) is a promising new online tool for 3D imaging during cardiac ablation procedures. No precise data exist concerning its associated radiation dose. The current study evaluated the effective dose (ED) of cardiac rotational angiography and its relation to patient properties, imaging system input settings, and quality of reconstructed 3D images. [ABSTRACT FROM PUBLISHER]

Aims: Follow-up of implantable cardioverter defibrillator (ICD) patients, with regular in-office visits every 3–6 months, puts a significant burden on specialized electrophysiology clinics. New technology allows for remote monitoring of device function. We wanted to investigate its potential reliability and to which extent its use can reduce in-office visits. [ABSTRACT FROM PUBLISHER]

Aims Spontaneous or inducible sustained ventricular arrhythmias (VA) in endurance athletes frequently originate from the right ventricle (RV), even in the absence of familial arrhythmogenic RV cardiomyopathy (ARVC). The goal of this study was to determine whether the RV arrhythmogenic predilection in these patients is associated with RV functional abnormalities. [ABSTRACT FROM PUBLISHER]

In this study we have included 222 patients with apparent neurally mediated syncope and with a positive diagnostic tilt test. The mean age was 33.4 ± 21.2 years (median 25.3): there were 107 men (median age 25.3) and 115 women (median age 22.6). The age difference between males and females was statistically significant (P = 0.002).The response to the diagnostic tilt test was: type 1 (mixed) in 74 patients; type 2A (cardioinhibitory and bradycardia) in 6; type 2B (cardioinhibitory and asystole) in 61; type 3 (vasodepressor) in 81.In all 222 patients the diagnostic tilt test was positive after 19 ± 11 min (mean ± SD), median time: 18 min. For the four types of syncope, the duration in minutes of the diagnostic tilt test was: type 1 (mixed) 19.5 ± 11.4; type 2A (cardioinhibitory) 24.8 ± 13.6; type 2B (cardioinhibitory and asystole) 14.7 ± 10.2; type 3 (vasodepressor) 21.6 ± 11.1. A significant difference was found between type 2B and type 3 responses (P = 0.002). Between males and females no significant differences in the duration of the diagnostic tilt test were found, neither for all responses, nor for the four subtypes.A type 2B (cardioinhibitory and asystole) response occurred in 61 patients. The duration of asystole was 12.8 ± 10.6 s (mean ± SD; median 9, minimum 3, maximum 60).The head-up tilt test was repeated day after day: one session per day. The response became negative at the second session in 119 patients (54%); at session 3 in 47 (21%); at session 4 in 30 (13%); at session 5 in 15 (7%); at session 6 in 6 (3%); at session 7 in 2 (1%); at session 8 in 3 (1%). For all 222 patients the mean number of sessions in order to obtain a negative tilt test was 2.9 (SD 1.3; median 2).Only 25% of patients remained tilt-positive for three or more sessions. A negative tilt test was ultimately obtained in every patient.Follow-up data are available for 202/222 patients. The time span between the first and last tilt test was 11.1 ± 10 months (median 8.8). Of these 202 patients, 163 remained free of any event (80.7%). [ABSTRACT FROM PUBLISHER]

Abstract: Background: Atrial fibrillation (AF) is associated with extracellular matrix remodeling involving atrial fibrosis and atrial dilatation. Angiotensin II mediated pathways and matrix metalloproteinases (MMPs) have been implicated in these processes. Our aim was to study atrial structural remodeling and the expression of the angiotensin receptor subtypes and MMPs and their inhibitors (TIMPs) in patients with mitral valve disease with and without AF. Methods and results: Biopsies from right and left atrial appendages (RA and LA) were taken from patients undergoing CABG (n =9, all in sinus rhythm (SR)) or mitral valve surgery (MVS; n =19; 9 with permanent AF and 10 in SR). Patients with MVS and AF had significantly larger atria (versus MVS and SR: p =0.02; versus CABG: p &#60;0.01). The MVS patients had significantly more fibrosis than the control CABG group. Fibrosis was increased in both the AF and SR MVS groups in the LA, but only in the MVS–AF group in the RA. These AF patients had significantly more tricuspid regurgitation than SR patients. MMP-1 was down-regulated in LA of MVS patients (p =0.02) independent of the underlying rhythm (SR or AF; p =0.95). In RA biopsies, MMP-1 was down-regulated only in the MVS and AF group. MMP-9 was down-regulated in the MVS patients compared to CABG both in the RA and LA, and without a difference between the SR and AF groups. Protein expression of AT-1, AT-2, MMP-2, TIMP-1, -2 and -4, TNF-α, and TNF-α-converting enzyme did not differ significantly between the 3 groups. Conclusions: Concordant changes between MMP-expression and fibrosis during mitral valve disease, both in LA and RA, suggest involvement of MMPs in structural atrial remodeling. AF itself did not contribute to altered fibrosis or MMP-expression in the LA. The association between AF and RA changes may be precipitated by greater hemodynamic load due to tricuspid regurgitation in these patients. [Copyright &y& Elsevier]

Background Electrocardiographic abnormalities and premature ventricular contractions are common in athletes and are generally benign. However, the specific outcome of high-level endurance athletes with frequent and complex ventricular arrhythmias is unclear. Also, information on the predictive accuracy of different investigations in this subgroup is unknown.Results We report on 46 high-level endurance athletes with ventricular arrhythmias (45 male; median age 31 years) followed-up for a median of 4.7 years. Eighty percent were cyclists. Hypertrophic cardiomyopathy or coronary abnormalities were present in ≤5%. Eighty percent of the arrhythmias had a left bundle branch morphology. Right ventricular (RV) arrhythmogenic involvement (based on a combination of multiple criteria) was manifest in 59% of the athletes, and suggestive in another 30%. Eighteen athletes developed a major arrhythmic event (sudden death in nine, all cyclists). They were significantly younger than those without event (median 23 years vs 38 years; P=0.01). Outcome could not be predicted by presenting symptoms, non-invasive arrhythmia evaluation or morphological findings at baseline. Only the induction of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF) during invasive electrophysiological testing was significantly related to outcome (RR 3.4; P=0.02). Focal arrhythmias were associated with a better prognosis than those due to reentry (P=0.02) but the mechanism could be determined in only 22 (48%).Conclusions Complex ventricular arrhythmias do not necessarily represent a benign finding in endurance athletes. An electrophysiological study is indicated for risk evaluation, both by defining inducibility and identifying the arrhythmogenic mechanism. Endurance athletes with arrhythmias have a high prevalence of right ventricular structural and/or arrhythmic involvement. Endurance sports seems to be related to the development and/or progression of the underlying arrhythmogenic substrate. [ABSTRACT FROM PUBLISHER]

As new algorithms are being developed to promote intrinsic atrioventricular conduction in preventing the deleterious effects of right ventricular pacing, more complex rhythm strips can be encountered. In our patient with a dual-chamber implantable cardioverter-defibrillator, such an algorithm resulted in a pacemaker-mediated tachycardia with several changes in cycle length. [ABSTRACT FROM PUBLISHER]

Sensing in pacemakers (PMs) and implantable cardioverter defibrillators (ICDs) is crucial to normal device behaviour. Since both devices treat different arrhythmias, the technical approach to signal detection is also completely different. A PM has a fixed threshold of sensing, above which events are sensed and therapy of the device withheld. On the other hand, the defibrillator has a variable threshold of sensing to detect tachyarrhythmias, with sometimes very small and changing electrogram amplitudes. In this case report, we describe interference between a PM and an ICD caused by these differences in the detection of cardiac events, leading to undersensing of ventricular fibrillation at defibrillation threshold testing. [ABSTRACT FROM PUBLISHER]