Understanding ventricular tachycardia : towards individualized substrate-based therapy

Patients with structural heart disease - e.g. after myocardial infarction or due to a cardiomyopathy - are at increased risk for sudden cardiac death because of arrhythmia. The department of Cardiology at the Leiden University Medical Center has a strong interest for the underlying substrate and mechanisms of ventricular arrhythmias. Since 2011, research fellow Sebastiaan Piers and his supervisor prof. dr. Katja Zeppenfeld have performed innovative studies, combining advanced electrophysiological data with detailed imaging data derived from CT and MRI. These studies have led to important insights into the substrate and mechanisms of ventricular arrhythmia in patients after myocardial infarction or with a cardiomyopathy. An improved understanding may be the most important prerequisite for the development of effective, individualized and substrate-based therapies for ventricular arrhythmias in the future. Sebastiaan Piers will defend his thesis "Understanding Ventricular Tachycardia: Towards Individualized Substrate-based Therapy" on Thursday January 28th 2016.The printing of this thesis was financially supported by St. Jude Medical, Biotronik, Bayer HealthCare, Sanofi Aventis, Chipsoft, Medis Medical Imaging and Toshiba Medical Systems. Het verschijnen van dit proefschrift werd mede mogelijk gemaakt door de steun van de Nederlandse Hartstichting en de Stichting Wetenschap en Onderzoek Interne Geneeskunde Onze Lieve Vrouwe Gasthuis.UBL - phd migration 201

Unipolar voltage mapping in right ventricular cardiomyopathy: pitfalls, solutions and advantages

Aims Endocardial unipolar and bipolar voltage mapping (UVM/BVM) of the right ventricle (RV) are used for transmural substrate delineation. However, far-field electrograms (EGMs) and EGM changes due to injury current may influence automatically generated UVM. Epicardial BVM is considered less accurate due to the impact of fat thickness (FT). Data on epicardial UVM are sparse. The aim of the study is two-fold: to assess the influence of the manually corrected window-of-interest on UVM and the potential role of epicardial UVM in RV cardiomyopathies.Methods and results Consecutive patients who underwent endo-epicardial RV mapping with computed-tomography (CT) integration were included. Mapping points were superimposed on short-axis CT slices and correlated with local FT. All points were manually re-analysed and the window-of-interest was adjusted to correct for false high unipolar voltage (UV). For opposite endo-epicardial point-pairs, endo-epicardial bipolar voltage (BV) and UV were correlated for different FT categories. A total of 3791 point-pairs of 33 patients were analysed. In 69% of endocardial points and 63% of epicardial points, the window-of-interest needed to be adjusted due to the inclusion of far-field EGMs, injury current components, or RV-pacing artifacts. The Pearson correlation between corrected endo-epicardial BV and UV was lower for point-pairs with greater FT; however, this correlation was much stronger and less influenced by fat for UV.Conclusion At the majority of mapping sites, the window-of-interest needs to be manually adjusted for correct UVM. Unadjusted UVM underestimates low UV regions. Unipolar voltage seems to be less influenced by epicardial fat, suggesting a promising role for UVM in epicardial substrate delineation.Cardiolog

The harm of delayed diagnosis of arrhythmogenic cardiac sarcoidosis: a case series

Aims Cardiac sarcoidosis (CS) is a known cause of ventricular tachycardia (VT). However, an arrhythmogenic presentation may not prompt immediate comprehensive evaluation. We aimed to assess the diagnostic and disease course of patients with arrhythmogenic cardiac sarcoidosis (ACS).Methods and results From the Leiden VT-ablation-registry, consecutive patients with CS as underlying aetiology were retrospectively included. Data on clinical presentation, time-to-diagnosis, cardiac function, and clinical outcomes were collected. Patients were divided in early (<6 months from first cardiac presentation) and late diagnosis. After exclusion of patients with known causes of non-ischaemic cardiomyopathy (NICM), 15 (12%) out of 129 patients with idiopathic NICM were ultimately diagnosed with CS and included. Five patients were diagnosed early; all had early presentation with VTs. Ten patients had a late diagnosis with a median delay of 24 (IQR 15-44) months, despite presentation with VT (n=5) and atrioventricular block (n=4). In 6 of 10 patients, reason for suspicion of ACS was the electroanatomical scar pattern. In patients with early diagnosis, immunosuppressive therapy was immediately initiated with stable cardiac function during follow-up. Adversely, in 7 of 10 patients with late diagnosis, cardiac function deteriorated before diagnosis, and in only one cardiac function recovered with immunosuppressive therapy. Six (40%) patients died (five of six with late diagnosis).Conclusion Arrhythmogenic cardiac sarcoidosis is an important differential diagnosis in NICM patients referred for VT ablation. Importantly, the diagnosis is frequently delayed, which leads to a severe disease course, including irreversible cardiac dysfunction and death. Early recognition, which can be facilitated by electroanatomical mapping, is crucial.Pathogenesis and treatment of chronic pulmonary disease

Early career perspectives of young Dutch cardiologists

Background There are nationwide concerns about the unemployment rate among young Dutch cardiologists and the increase in temporary positions. Therefore, the aim of this study was to investigate the unemployment rate in this subgroup as well as the length of time between the end of their training and the acquisition of a permanent position. Methods All cardiologists who completed their training between January 2015 and December 2018 were invited to fill in an online questionnaire about their demographic characteristics, professional profile and employment status. The unemployment rate was calculated and Kaplan-Meier curves were used to determine the time between the end of training and the first permanent contract. Results In total, 174 participants were included (mean age 35 +/- 3 years, 64% male, median follow-up 2.3 years (interquartile range 1.4-3.2 years)). The unemployment rate was 0.6% (n = 1). Only 12 participants (7%) started their career with a permanent position. The percentage of cardiologists with a temporary position was 82%, 61% and 33% at 1, 2 and 3 years, respectively. The percentage of cardiologists with a temporary position did not differ with regard to age, gender, holding a PhD degree or type of teaching institution attended (academic vs non-academic). Forty-four per cent of participants perceived the current job market to be problematic. Conclusions The unemployment rate among young cardiologists in the Netherlands was low between 2015 and 2018. The vast majority of cardiologists start their career on a temporary contract. Three years later, 33% still hold temporary positions. Due to the resultant job insecurity, many young cardiologists describe the job market as problematic.Cardiolog

Electroanatomical Voltage Mapping to Distinguish Right-Sided Cardiac Sarcoidosis From Arrhythmogenic Right Ventricular Cardiomyopathy

OBJECTIVES This study sought to investigate the value of electroanatomical voltage mapping (EAVM) to distinguish cardiac sarcoidosis (CS) from arrhythmogenic right ventricular cardiomyopathy (ARVC) in patients with ventriculartachycardia from the right ventricle (RV).BACKGROUND CS can mimic ARVC. Because scar in ARVC is predominantly subepicardial, this study hypothesized that the relative sizes of endocardial low bipolar voltage (BV) to low unipolar voltage (UV) areas may distinguish CS from ARVC.METHODS Patients with CS affecting the RV (n = 14), patients with gene-positive ARVC (n = 13), and a reference group of patients without structural heart disease (n = 9) who underwent RV endocardial EAVM were included. RV regionspecific BV and UV cutoffs were derived from control subjects. In CS and ARVC, segmental involvement was determined and low-voltage areas were measured, using RESULTS In control subjects, BV and UV varied significantly among RV regions. The basal septum was involved in 71% of CS patients and in none of ARVC patients. Ratio5.5 discriminated CS from ARVC the best. An algorithm including Ratio5.5≥0.45 and basal septal involvement identified CS with 93% sensitivity and 85% specificity. This was validated in a separate population (CS [n = 6], ARVC [n = 10]) with 100% sensitivity and 100% specificity.CONCLUSIONS EAVM provides detailed information about scar characteristics and scar distribution in the RV. An algorithm combining Ratio5.5 (area BV Cardiolog

The arrhythmogenic cardiomyopathy phenotype associated with PKP2 c.1211dup variant

BackgroundThe arrhythmogenic cardiomyopathy (ACM) phenotype, with life-threatening ventricular arrhythmias and heart failure, varies according to genetic aetiology. We aimed to characterise the phenotype associated with the variant c.1211dup (p.Val406Serfs*4) in the plakophilin-2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants.MethodsClinical data were collected retrospectively from medical records of 106 PKP2 c.1211dup heterozygous carriers. Using data from the Netherlands ACM Registry, c.1211dup was compared with 3 other truncating PKP2 variants (c.235C > T (p.Arg79*), c.397C > T (p.Gln133*) and c.2489+1G > A (p.?)).ResultsOf the 106 carriers, 47 (44%) were diagnosed with ACM, at a mean age of 41 years. By the end of follow-up, 29 (27%) had experienced sustained ventricular arrhythmias and 12 (11%) had developed heart failure, with male carriers showing significantly higher risks than females on these endpoints (p < 0.05). Based on available cardiac magnetic resonance imaging and echocardiographic data, 46% of the carriers showed either right ventricular dilatation and/or dysfunction, whereas a substantial minority (37%) had some form of left ventricular involvement. Both geographical distribution of carriers and haplotype analysis suggested PKP2 c.1211dup to be a founder variant originating from the South-Western coast of the Netherlands. Finally, a Cox proportional hazards model suggested significant differences in ventricular arrhythmia-free survival between 4 PKP2 founder variants, including c.1211dup.ConclusionsThe PKP2 c.1211dup variant is a Dutch founder variant associated with a typical right-dominant ACM phenotype, but also left ventricular involvement, and a possibly more severe phenotype than other Dutch PKP2 founder variants.Cardiolog

Understanding ventricular tachycardia : towards individualized substrate-based therapy

Patients with structural heart disease - e.g. after myocardial infarction or due to a cardiomyopathy - are at increased risk for sudden cardiac death because of arrhythmia. The department of Cardiology at the Leiden University Medical Center has a strong interest for the underlying substrate and mechanisms of ventricular arrhythmias. Since 2011, research fellow Sebastiaan Piers and his supervisor prof. dr. Katja Zeppenfeld have performed innovative studies, combining advanced electrophysiological data with detailed imaging data derived from CT and MRI. These studies have led to important insights into the substrate and mechanisms of ventricular arrhythmia in patients after myocardial infarction or with a cardiomyopathy. An improved understanding may be the most important prerequisite for the development of effective, individualized and substrate-based therapies for ventricular arrhythmias in the future. Sebastiaan Piers will defend his thesis "Understanding Ventricular Tachycardia: Towards Individualized Substrate-based Therapy" on Thursday January 28th 2016.</p

Bipolar Ablation of Ventricular Tachycardia in a Patient After Atrial Switch Operation for Dextro-Transposition of the Great Arteries

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Bipolar ablation of ventricular tachycardia in a patient after atrial switch operation for dextro-transposition of the great arteries

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Automated left ventricle segmentation in late gadolinium-enhanced MRI for objective myocardial scar assessment

Cardiolog