Novel use of repolarization parameters in electrocardiographic imaging to uncover arrhythmogenic substrate.

BACKGROUND: Measuring repolarization characteristics is challenging and has been reserved for experienced physicians. In electrocardiographic imaging (ECGI), activation-recovery interval (ARI) is used as a measure of local cardiac repolarization duration. We hypothesized that repolarization characteristics, such as local electrogram morphology and local and global dispersion of repolarization timing and duration could be of significance in ECGI. OBJECTIVE: To further explore their potential in arrhythmic risk stratification we investigated the use of novel repolarization parameters in ECGI. MATERIALS AND METHODS: We developed and compared methods for T-peak and T-end detection in reconstructed potentials. All methods were validated on annotated reconstructed electrograms (EGMs). Characteristics of the reconstructed EGMs and epicardial substrate maps in IVF patients were analyzed by using data recorded during sinus rhythm. The ECGI data were analyzed for EGM morphology, conduction, and repolarization. RESULTS: We acquired ECGI data from 8 subjects for this study. In all patients we evaluated four repolarization parameters: Repolarization time, T-wave area, Tpeak-Tend interval, and T-wave alternans. Most prominent findings were steep repolarization time gradients in regions with flat EGMs. These regions were also characterized by low T-wave area and large differences in Tpeak-Tend interval. CONCLUSIONS: Measuring novel repolarization parameters in reconstructed electrograms acquired with ECGI is feasible, can be done in a fully automated manner and may provide additional information on underlying arrhythmogenic substrate for risk stratification. Further studies are needed to investigate their potential use and clinical application.

Life-long tailoring of diagnosis and management of patients with idiopathic ventricular fibrillation-future perspectives in research.

The diagnosis and management of idiopathic ventricular fibrillation is challenging, as it requires extensive diagnostic testing and offers few curative options due to unknown underlying disease. The resulting population is a heterogeneous group of patients with a largely unknown natural history. Structural patient characterisation, follow-up and innovations in diagnostic testing can improve our understanding of the disease mechanisms of idiopathic ventricular fibrillation, detect underlying disease during follow-up and aid in therapeutic management. Recently, initiatives have been launched in the Netherlands to investigate the role of high-resolution non-invasive electrocardiographic imaging and genetic and familial screening in idiopathic ventricular fibrillation.

A decade of atrial fibrillation ablation : Shifts in patient characteristics and procedural outcomes.

BACKGROUND: Over the past decade, radiofrequency catheter ablation (RFCA) of atrial fibrillation (AF) has evolved into a frequently performed procedure. The aim of this study was to monitor changes in patient characteristics, procedural characteristics, outcomes and complications over the past 10 years. METHODS: All consecutive patients who underwent primary RFCA treatment of AF in the University Medical Center Utrecht from 2005-2015 were included. In all patients, the primary ablation strategy was pulmonary vein (PV) antrum isolation without additional substrate modification. Baseline patient and procedure characteristics, and 1­year follow-up data of 975 patients were prospectively collected. RESULTS: In 2005, 73.4% of patients suffered from paroxysmal AF, which decreased to 45.3% in 2014. Mean age increased from 54 ± 9 to 61 ± 10 years and CHA2DS2-VASc score ≥2 from 18 to 40.6%. History of AF decreased significantly from 7 to 4 years. Mean procedure duration was 237 ± 53 min in 2005 and 163 ± 41 min in 2014. Fluoroscopy time significantly decreased from 41 ± 17 to 19 ± 8 min and total radiation exposure from 465 (263-687) to 210 (118-376) mGy. One-year success remained similar (2005: 55.6%, 2014: 54.8%), as did the amount of PV reconnection observed during redo procedures. Due to a marked reduction in vascular complications and moderate PV stenosis, the total complication rate decreased significantly. CONCLUSION: Over the past decade, AF ablation has increasingly been performed in older patients with persistent AF and more comorbidity. Moreover, it has been performed earlier after AF diagnosis. Although several performance parameters, such as procedure duration and complication rate, improved, 1­year single procedure success remained unchanged.

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.

[High time for a total ban on smoking in the hotel, restaurant and catering industry: the arguments are mounting]. / Hoogste tijd voor een rookvrije horeca: de argumenten stapelen zich op.

Active and passive smoking are well-known causes of disease, including respiratory and cardiovascular disease and cancer. In 2004 the Dutch government introduced new legislation to regulate smoking in the workplace. However, smoking is still allowed in hotels, bars and restaurants, despite the fact that two-thirds of the Dutch population support a total ban on smoking in public places. Several other European countries and American states have banned smoking in public places. Studies performed in these regions show that the new smoking regulations have had no negative economic effects. Moreover, various studies have shown that smoking bans have a positive impact on public health, even in the short-term, including a significant decrease in respiratory and cardiovascular disease. There is therefore no reason to continue to exclude hotels, bars and restaurants from the smoking ban in all public places in The Netherlands.

The human adult cardiomyocyte phenotype.

AIM: Determination of the phenotype of adult human atrial and ventricular myocytes based on gene expression and morphology. METHODS: Atrial and ventricular cardiomyocytes were obtained from patients undergoing cardiac surgery using a modified isolation procedure. Myocytes were isolated and cultured with or without serum. The relative cell attachment promoting efficiency of several reagents was evaluated and compared. Morphological changes during long-term culture were assessed with phase contrast microscopy, morphometric analysis and immunocytochemistry or RT-PCR of sarcomeric markers including alpha-actinin, myosin light chain-2 (MLC-2) and the adhesion molecule, cadherin. RESULTS: The isolation method produced viable rod-shaped atrial (16.6+/-6.0%, mean+/-S.E.; n=5) and ventricular cells (22.4+/-8.0%, mean+/-S.E.; n=5) in addition to significant numbers of apoptotic and necrotic cells. Cell dedifferentiation was characterized by the loss of sarcomeric structure, condensation and extrusion of sarcomeric proteins. Cells cultured with low serum recovered and assumed a flattened, spread form with two distinct morphologies apparent. Type I cells were large, had extensive sarcolemmal spreading, with stress fibers and nascent myofibrils, whilst type II cells appeared smaller, with more mature myofibril organisation and focal adhesions. CONCLUSION: Characterization of the redifferentiation capabilities of cultured adult cardiac myocytes in culture, provides an important system for comparing cardiomyocytes differentiating from human stem cells and provides the basis for an in vitro transplantation model to study interaction and communication between primary adult and stem cell-derived cardiomyocytes.

Impaired autonomic function predicts dizziness at onset of paroxysmal atrial fibrillation.

BACKGROUND: Paroxysmal atrial fibrillation is associated with various symptoms, including dizziness, which presumably reflects hemodynamic deterioration. Given the importance of the autonomic nervous system in mitigating the hemodynamic effect of atrial fibrillation, we hypothesized that autonomic function would be predictive of the severity of dizziness. METHODS: The study group comprised 73 patients with paroxysmal atrial fibrillation (mean age 54.1 years, 51 males). Forty-three (59%) patients had lone atrial fibrillation. Mean ventricular rate during atrial fibrillation was 99+/-16 beats/min. On average, patients had a 3-year history of one paroxysm per week lasting 2 h. Autonomic function was assessed using autonomic function tests, including noninvasive measurement of baroreflex sensitivity. Head up tilting was used to test vasovagal reactivity. Severity of dizziness at onset of atrial fibrillation was quantified by the patients using a five-point scale (1=none; 2=light; 3=mild; 4=moderate; and 5=severe). Multivariate analysis was performed to identify the independent predictors of the severity of dizziness. RESULTS: Mean severity of dizziness was 3.36+/-1.65. Multivariate predictors of moderate-to-severe dizziness as opposed to none-to-mild dizziness were a low 30-15 ratio after standing up and low baroreflex sensitivity. Though syncope was never reported nine patients showed a full vasovagal response during head up tilting. CONCLUSIONS: It is concluded that dizziness in patients with "treated" atrial fibrillation in the setting of none to mild structural heart disease is predicted by impaired autonomic function. Vasovagal reactivity appears not to be involved in this connection.

New and viable cells to replace lost and malfunctioning myocardial tissue.

The use of stem cells for cardiac repair is a promising opportunity for developing new treatment strategies as the applications are theoretically unlimited and lead to actual cardiac tissue regeneration. Human embryonic stem cells were only recently cloned and their capacity to differentiate into true cardiomyocytes makes them in principle an unlimited source of transplantable cells for cardiac repair, although practical and ethical constraints exist. Also, the study of embryonic stem cells and their differentiation into cardiomyocytes will bring forth new insights into the molecular processes involved in cardiomyocyte-development and -proliferation, which could lead to the development of other strategies to augment in vivo cardiomyocyte numbers. On the other hand, somatic stem cells are alternative cell sources that can be used for cell transplantation purposes. They do not evoke ethical issues and bear less ethical constraints. However, they also appear to be much more restricted in their differentiation potential than the embryonic stem cells. Here we discuss the use of both cell types, embryonic and somatic stem cells, in relation with their importance for the clarification of cardiomyocyte-development and their possible usefulness for clinical therapy.

[Hypertrophic cardiomyopathy: from diagnosis to prevention]. / Hypertrofische cardiomyopathie: van diagnostiek naar preventie.

In a 55-year-old man, his two sons aged 32 and 30 years and a 3-year-old grandchild, a gene mutation related to an increased chance of hypertrophic cardiomyopathy was found. The adults had complaints of cardiac arrhythmias varying from dizziness to cardiac arrest and received medication; a defibrillator was also implanted in the case of the sons. Familial hypertrophic cardiomyopathy can be diagnosed in an early stage with DNA screening methods. At that time 'patients' (carriers) often do not exhibit symptoms. This offers the possibility of taking therapeutic measures to prevent or slow down the disease process. However, the scientific basis for preventive therapy is inadequate, so that medical-ethical dilemmas arise which can affect the decision-making process with respect to genetic testing. Additional research must lead to satisfactory preventive therapies, so that in the future the genetic diagnosis 'hypertrophic cardiomyopathy' can be effectively translated into disease prevention.

Expression of a transgene encoding mutant p193/CUL7 preserves cardiac function and limits infarct expansion after myocardial infarction.

BACKGROUND: Transgenic mice expressing the dominant interfering p193 protein in cardiomyocytes (MHC-1152stop mice) exhibit an induction of cell cycle activity and altered remodelling after experimental myocardial infarction (MI). OBJECTIVE: To determine whether the altered remodelling results in improved cardiac function in the MHC-1152stop mice after MI, as compared with non-transgenic mice. METHODS: MHC-1152stop mice and non-transgenic littermates were subjected to experimental MI via permanent occlusion of the coronary artery. Infarct size was determined at 24 h and at 4 weeks after MI, and left ventricular pressure-volume measurements were performed at 4 weeks after MI in infarcted and sham-operated animals. RESULTS: Infarct size in MHC-1152stop mice and non-transgenic littermates was not statistically different at 24 h after MI, as measured by tetrazolium staining. Morphometric analysis showed that infarct scar expansion at 4 weeks after MI was reduced by 10% in the MHC-1152stop mice (p<0.05). No differences in cardiac function were detected between sham-operated MHC-1152stop mice and their non-transgenic littermates. However, at 4 weeks after MI, the ventricular isovolumic relaxation time constant (tau) was decreased by 19% (p<0.05), and the slope of the dP/dt(max)-EDV relationship was increased 99% (p<0.05), in infarcted MHC-1152stop mice as compared with infarcted non-transgenic littermates. CONCLUSION: Expression of the dominant interfering p193 transgene results in a decrease in infarct scar expansion and preservation of myocardial function at 4 weeks after MI. Antagonism of p193 activity may represent an important strategy for the treatment of MI.

Quality of life in patients with paroxysmal atrial fibrillation and its predictors: importance of the autonomic nervous system.

AIMS: To determine the impact of paroxysmal atrial fibrillation on quality of life and to determine the predictors of quality of life, particularly the role of symptomatology and autonomic function. METHODS AND RESULTS: The study group comprised 73 patients with paroxysmal atrial fibrillation (mean age 54.1 years, 51 males). On average, patients had a 3-year history of one paroxysm per week lasting 2 h. Quality of life was assessed using the SF-36 (Medical Outcomes Study Short-Form Health Survey) and compared with age-matched controls. Autonomic function was assessed using Holter monitoring with analysis of heart rate variability and autonomic function tests. Symptoms during paroxysms of atrial fibrillation were also scored. Multivariate analysis was performed to identify independent predictors of quality of life. Quality of life scores were markedly lower in patients than in controls in four of the eight subscales (P<0.001): physical role function, emotional role function, vitality and general health. Structural heart disease did not predict quality of life, whereas frequency of paroxysms was predictive only of physical role function. In contrast, autonomic variables (baroreflex-sensitivity, total power (heart rate variability), response to deep breathing, 30-15 ratio (standing up)) were predictive in all four respective subscales (P<0.05), depressed vagal function being predictive of low scores. Symptoms, particularly severe perspiration, were also predictive of low scores (P<0.05). CONCLUSIONS: This study shows that paroxysmal atrial fibrillation causes significant impairment of quality of life. Further, symptomatology and autonomic function are important predictors of quality of life in this patient group.