Comparing adolescent- and adult-onset unexplained cardiac arrest: Results from the Dutch Idiopathic VF Registry.

BACKGROUND: Current cohorts of patients with idiopathic ventricular fibrillation (IVF) primarily include adult-onset patients. Underlying causes of sudden cardiac arrest vary with age; therefore, underlying causes and disease course may differ for adolescent-onset vs adult-onset patients. OBJECTIVE: The purpose of this study was to compare adolescent-onset with adult-onset patients having an initially unexplained cause of VF. METHODS: The study included 39 patients with an index event aged ≤19 years (adolescent-onset) and 417 adult-onset patients from the Dutch Idiopathic VF Registry. Data on event circumstances, clinical characteristics, change in diagnosis, and arrhythmia recurrences were collected and compared between the 2 groups. RESULTS: In total, 42 patients received an underlying diagnosis during follow-up (median 7 [2-12] years), with similar yields (15% adolescent-onset vs 9% adult-onset; P = .16). Among the remaining unexplained patients, adolescent-onset patients (n = 33) had their index event at a median age of 17 [16-18] years, and 72% were male. The youngest patient was aged 13 years. In comparison with adults (n = 381), adolescent-onset patients more often had their index event during exercise (P <.01). Adolescent-onset patients experienced more appropriate implantable cardioverter-defibrillator (ICD) therapy during follow-up compared with adults (44% vs 26%; P = .03). Inappropriate ICD therapy (26% vs 17%; P = .19), ICD complications (19% vs 14%; P = .41), and deaths (3% vs 4%; P = 1) did not significantly differ between adolescent-onset and adult-onset patients. CONCLUSION: IVF may occur during adolescence. Adolescent-onset patients more often present during exercise compared with adults. Furthermore, they are more vulnerable to ventricular arrhythmias as reflected by a higher incidence of appropriate ICD therapy.

Reduced kinase function in two ultra-rare TNNI3K variants in families with congenital junctional ectopic tachycardia.

Genetic missense variants in TNNI3K, encoding troponin-I interacting kinase, have been associated with dilated cardiomyopathy (DCM) and observed in families with supraventricular tachycardias (SVT). Previously, a family harboring the TNNI3K-c.1615A > G (p.Thr539Ala) variant presented with congenital junctional ectopic tachycardia (CJET), an arrhythmia that arises from the atrioventricular (AV) node and His bundle. However, this was a relatively small four-generational family with limited genetic testing (N = 3). We here describe a multigenerational family with CJET harboring a novel ultra-rare TNNI3K variant: TNNI3K-c.1729C > T (p.Leu577Phe). Of all 18 variant carriers, 13 individuals presented with CJET, resulting in a genetic penetrance of 72%. In addition, CJET is reported in another small family harboring TNNI3K-c.2225C > T (p.Pro742Leu). Similar to the previously published CJET family, both TNNI3K variants demonstrate a substantial reduction of kinase activity. Our study contributes novel evidence supporting the involvement of TNNI3K genetic variants as significant contributors to CJET, shedding light on potential mechanisms underlying this cardiac arrhythmia.

The genetic basis of apparently idiopathic ventricular fibrillation: a retrospective overview.

AIMS: During the diagnostic work-up of patients with idiopathic ventricular fibrillation (VF), next-generation sequencing panels can be considered to identify genotypes associated with arrhythmias. However, consensus for gene panel testing is still lacking, and variants of uncertain significance (VUS) are often identified. The aim of this study was to evaluate genetic testing and its results in idiopathic VF patients. METHODS AND RESULTS: We investigated 419 patients with available medical records from the Dutch Idiopathic VF Registry. Genetic testing was performed in 379 (91%) patients [median age at event 39 years (27-51), 60% male]. Single-gene testing was performed in 87 patients (23%) and was initiated more often in patients with idiopathic VF before 2010. Panel testing was performed in 292 patients (77%). The majority of causal (likely) pathogenic variants (LP/P, n = 56, 15%) entailed the DPP6 risk haplotype (n = 39, 70%). Moreover, 10 LP/P variants were found in cardiomyopathy genes (FLNC, MYL2, MYH7, PLN (two), TTN (four), RBM20), and 7 LP/P variants were identified in genes associated with cardiac arrhythmias (KCNQ1, SCN5A (2), RYR2 (four)). For eight patients (2%), identification of an LP/P variant resulted in a change of diagnosis. In 113 patients (30%), a VUS was identified. Broad panel testing resulted in a higher incidence of VUS in comparison to single-gene testing (38% vs. 3%, P < 0.001). CONCLUSION: Almost all patients from the registry underwent, albeit not broad, genetic testing. The genetic yield of causal LP/P variants in idiopathic VF patients is 5%, increasing to 15% when including DPP6. In specific cases, the LP/P variant is the underlying diagnosis. A gene panel specifically for idiopathic VF patients is proposed.

One-Year Mortality in Patients Undergoing an Implantable Cardioverter Defibrillator or Cardiac Resynchronization Therapy Pulse Generator Replacement: Identifying Patients at Risk.

Implantable cardioverter defibrillators (ICDs) significantly contribute to the prevention of sudden cardiac death in selected patients. However, it is essential to identify those who are likely to not have benefit from an ICD and to defer a pulse generator exchange. Easily implementable guidelines for individual risk stratification and decision making are lacking. This study investigates the 1-year mortality of patients who underwent an ICD or cardiac resynchronization therapy with defibrillator function (CRT-D) pulse generator replacement in a contemporary real-world tertiary hospital setting. The cause of death and patient- and procedure-related factors are stratified, and predictive values for 1-year mortality are evaluated. Patients with a follow-up of ≥365 days (or prior mortality) after an ICD or CRT-D exchange at the Leiden University Medical Center from 1 January 2018 until 31 December 2021 were eligible. In total, 588 patients were included (77% male, 69 [60-76] years old, 59% primary prevention, 46% ischemic cardiomyopathy and 37% mildly reduced left ventricular ejection fraction (LVEF)). Patients undergoing a CRT-D replacement or upgrade had a significantly higher 1-year all-cause mortality (10.7% and 11.9%, respectively) compared to patients undergoing ICD (2.8%) exchange (p = 0.002). LVEF ≤ 30%, New York Heart Association class ≥ 3, estimated glomerular filtration rate ≤ 30 mL/min/m2 and haemoglobin ≤ 7 mmol/L were independently associated with mortality within 1 year after pulse generator replacement. There is a growing need for prospectively validated risk scores to weight individualized risk of mortality with the expected ICD therapy benefit and to support a well-informed, shared decision-making process.

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

BACKGROUND: The 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 plakophilin­2 gene (PKP2) and compare it with previously reported Dutch PKP2 founder variants. METHODS: Clinical 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.?)). RESULTS: Of 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. CONCLUSIONS: The 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.

Importance of Systematic Diagnostic Testing in Idiopathic Ventricular Fibrillation: Results From the Dutch iVF Registry.

BACKGROUND: Idiopathic ventricular fibrillation (iVF) is a diagnosis of exclusion. Systematic diagnostic testing is important to exclude alternative causes for VF. The early use of "high yield" testing, including cardiac magnetic resonance (CMR), exercise testing, and sodium channel blocker provocation, has been increasingly recognized. OBJECTIVES: The purpose of this study was to investigate the importance and consistency of systematic diagnostic testing in iVF. METHODS: This study included 423 iVF patients from 11 large secondary and tertiary hospitals in the Netherlands. Clinical characteristics and diagnostic testing data were ascertained. RESULTS: IVF patients experienced the index event at a median age of 40 years (IQR: 28-52 years), and 61% were men. The median follow-up time was 6 years (IQR: 2-12 years). Over the years, "high yield" diagnostic tests were increasingly performed (mean 68% in 2000-2010 vs 75% in 2011-2021; P < 0.001). During follow-up, 38 patients (9%) originally labeled as iVF received an alternative diagnosis. Patients in whom "high-yield" diagnostic tests were consistently performed during the initial work-up received an alternative diagnosis less frequently during follow-up (HR: 0.439; 95% CI: 0.219-0.878; P = 0.020). Patients who received an alternative diagnosis during follow-up had a worse prognosis in terms of cardiac death (P = 0.012) with a trend toward more implantable cardioverter-defibrillator therapy (P = 0.055). CONCLUSIONS: Although adherence to (near) complete diagnostic testing in this population of iVF patients increased over the years, patients with iVF still undergo varying levels of diagnostic evaluation. The latter leads to initial underdiagnosis of alternative conditions and is associated with a worse prognosis. Our results underscore the importance of early systematic diagnostic assessment in patients with apparent iVF.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin (DSP) Truncating Variant.

BACKGROUND: Truncating variants in desmoplakin (DSPtv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of DSPtv cardiomyopathy. METHODS: Individuals with DSPtv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers. Clinical data and family history information were collected. Event-free survival from ventricular arrhythmia was assessed. Variant location was compared between cases and controls, and literature review of reported DSPtv performed. RESULTS: There were 98 probands and 72 family members (mean age at diagnosis 43±8 years, 59% women) with a DSPtv, of which 146 were considered clinically affected. Ventricular arrhythmia (sudden cardiac arrest, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy) occurred in 56 (33%) individuals. DSPtv location and proband status were independent risk factors for ventricular arrhythmia. Further, gene region was important with variants in cases (cohort n=98; Clinvar n=167) more likely to occur in the regions resulting in nonsense mediated decay of both major DSP isoforms, compared with n=124 genome aggregation database control variants (148 [83.6%] versus 29 [16.4%]; P<0.0001). CONCLUSIONS: In the largest series of individuals with DSPtv, we demonstrate that variant location is a novel risk factor for ventricular arrhythmia, can inform variant interpretation, and provide critical insights to allow for precision-based clinical management.

Reclassification of a likely pathogenic Dutch founder variant in KCNH2; implications of reduced penetrance.

BACKGROUND: Variants in KCNH2, encoding the human ether a-go-go (hERG) channel that is responsible for the rapid component of the cardiac delayed rectifier K+ current (IKr), are causal to long QT syndrome type 2 (LQTS2). We identified eight index patients with a new variant of unknown significance (VUS), KCNH2:c.2717C > T:p.(Ser906Leu). We aimed to elucidate the biophysiological effect of this variant, to enable reclassification and consequent clinical decision-making. METHODS: A genotype-phenotype overview of the patients and relatives was created. The biophysiological effects were assessed independently by manual-, and automated calibrated patch clamp. HEK293a cells expressing (i) wild-type (WT) KCNH2, (ii) KCNH2-p.S906L alone (homozygous, Hm) or (iii) KCNH2-p.S906L in combination with WT (1:1) (heterozygous, Hz) were used for manual patching. Automated patch clamp measured the variants function against known benign and pathogenic variants, using Flp-In T-rex HEK293 KCNH2-variant cell lines. RESULTS: Incomplete penetrance of LQTS2 in KCNH2:p.(Ser906Leu) carriers was observed. In addition, some patients were heterozygous for other VUSs in CACNA1C, PKP2, RYR2 or AKAP9. The phenotype of carriers of KCNH2:p.(Ser906Leu) ranged from asymptomatic to life-threatening arrhythmic events. Manual patch clamp showed a reduced current density by 69.8 and 60.4% in KCNH2-p.S906L-Hm and KCNH2-p.S906L-Hz, respectively. The time constant of activation was significantly increased with 80.1% in KCNH2-p.S906L-Hm compared with KCNH2-WT. Assessment of KCNH2-p.S906L-Hz by calibrated automatic patch clamp assay showed a reduction in current density by 35.6%. CONCLUSION: The reduced current density in the KCNH2-p.S906L-Hz indicates a moderate loss-of-function. Combined with the reduced penetrance and variable phenotype, we conclude that KCNH2:p.(Ser906Leu) is a low penetrant likely pathogenic variant for LQTS2.

Comparative analysis of right ventricular strain in Fabry cardiomyopathy and sarcomeric hypertrophic cardiomyopathy.

AIMS: To perform a comparative analysis of right ventricle (RV) myocardial mechanics, assessed by 2D speckle-tracking echocardiography (2D-STE), between patients with Fabry disease and patients with sarcomeric disease. METHODS AND RESULTS: Patients with Fabry cardiomyopathy (FC) (n = 28) were compared with patients with sarcomeric hypertrophic cardiomyopathy (HCM), matched for degree of left ventricle hypertrophy (LVH) and demographic characteristics (n = 112). In addition, patients with Fabry disease and no LVH [phenotype-negative carriers of pathogenic α-galactosidase gene mutations (GLA LVH-)] (n = 28) were compared with age and sex-matched carriers of sarcomeric gene mutations without LVH [Phenotype-negative carriers of pathogenic sarcomeric gene mutations (Sarc LVH-)] (n = 56). Standard echocardiography and 2D-STE were performed in all participants. Despite a subtle impairment of RV global longitudinal strain (RV-GLS) was common in both groups, patients with FC showed a more prominent reduction of RV free wall longitudinal strain (RV-FWS) and lower values of difference between RV-FWS and RV-GLS (ΔRV strain), in comparison to individuals with HCM (P < 0.001 and P = 0.002, respectively). RV-FWS and ΔRV strain demonstrated an independent and additive value in discriminating FC from HCM, over the presence of symmetric LVH, systolic anterior motion of the mitral valve and RV hypertrophy. Similar results were found in GLA LVH- patients: they had worse RV-FWS and lower values of ΔRV strain as compared to Sarc LVH- patients (both P < 0.001). CONCLUSION: Patients with FC show a specific pattern of RV myocardial mechanics, characterized by a larger impairment of RV-FWS and lower ΔRV strain in comparison to patients with HCM, which may be helpful in the differential diagnosis between these two diseases.

Sacral abnormalities including caudal appendage, skeletal dysplasia, and prenatal cardiomyopathy associated with a pathogenic TAB2 variant in a 3-generation family.

Haplo-insufficiency of the TGFß-activated kinase 1 binding protein 2 (TAB2) gene is associated with short stature, facial dysmorphisms, connective tissue abnormalities, hearing loss, and cardiac disease. Skeletal dysplasia and sacral dimples are also found in a minority of patients. Here, we describe a 3-generation family with caudal appendage, other sacral anomalies, and skeletal abnormalities including hypoplasia of the iliac wings and scapulae, fusion of the carpal bones and stenosis of the spinal canal, as well as a remarkable course of prenatally-detected cardiomyopathy with characteristics changing over time. Genetic analysis showed a heterozygous nonsense variant in the TAB2 gene.

Effects of Left Bundle Branch Block and Pacemaker Implantation on Left Ventricular Systolic Function After Transcatheter Aortic Valve Implantation.

Permanent pacemaker implantation (PPI) and left bundle branch block (LBBB) frequency after transcatheter aortic valve implantation (TAVI) and their effect on left ventricular ejection fraction (LVEF) remain controversial. We evaluated the incidence of PPI and new-onset LBBB after TAVI and their impact on LVEF at 6-month follow-up. Moreover, the impact of right ventricular (RV) pacing burden on changes in LVEF after TAVI was analyzed. The electrocardiograms of 377 patients (age 80 ± 7 years, 52% male) treated with TAVI were collected at baseline, after the procedure, at discharge, and at each outpatient follow-up. LVEF was measured at baseline before TAVI and 6 months after the procedure. Patients were divided into 3 groups according to the occurrence of LBBB, the need for PPI, or the absence of new conduction abnormalities. In patients with PPI, the influence of RV pacing burden on LVEF was analyzed. New-onset LBBB after TAVI occurred in 92 patients (24%), and PPI was required in 55 patients (15%). In patients without new conduction abnormalities, LVEF significantly increased during follow-up (56 ± 14% to 61 ± 12%, p <0.001). Patients with a baseline LVEF ≤50% presented with a significant recovery in LVEF, although the recovery was less pronounced in patients with new-onset LBBB. Moreover, patients with a baseline LVEF ≤50% who received PPI showed an improvement in LVEF at 6 months regardless of the RV pacing burden. New-onset LBBB hampers the recovery of LVEF after TAVI. Among patients with an LVEF ≤50%, pressure overload relief counteracts the effects of new-onset LBBB or RV pacing.

Left atrioventricular coupling index in hypertrophic cardiomyopathy and risk of new-onset atrial fibrillation.

BACKGROUNDS: This study aimed to investigate the association between left atrioventricular coupling index (LACI) and the occurrence of atrial fibrillation (AF) in patients with hypertrophic cardiomyopathy (HCM). METHODS: A total of 373 patients with HCM and no history of AF were evaluated by transthoracic echocardiography. LACI was defined by the ratio of left atrial (LA) end-diastolic volume divided by left ventricular (LV) end-diastolic volume. The cut-off value for LACI (≥40%) to identify LA-LV uncoupling was chosen based on the risk excess of new-onset AF described with a spline curve analysis. RESULTS: The median LACI was 37.5% (IQR: 24.4-56.7) and LA-LV uncoupling (LACI ≥40%) was observed in 171 (45.8%) patients. During a median follow-up of 11 (IQR 7-15) years, 118 (31.6%) subjects developed new-onset AF. The cumulative event-free survival at 10 years was 53% for patients with LA-LV uncoupling versus 94% for patients without LA-LV uncoupling (p < 0.001). Multivariable Cox regression analyses performed separately for each LA parameter showed an independent association between new-onset AF and LACI (hazard ratio [HR], 1.021; 95% CI, 1.017-1.026), LA maximum volume indexed (HR, 1.028; 95% CI, 1.017-1.039), LA minimum volume indexed (HR, 1.047; 95% CI, 1.037-1.060) and LA emptying fraction (HR, 0.967; 95% CI, 0.959-0.977, all p < 0.001). The inclusion of LACI in the multivariate model provided a larger improvement in the risk stratification for new-onset AF, as compared to conventional LA parameters. CONCLUSION: In patients with HCM, LACI was more predictive of the occurrence of new-onset AF than conventional LA parameters.

Five cases of complete atrioventricular block induced by bending forward: unusual but not unique.

AIMS: We describe five patients with syncope caused by a complete atrioventricular block (AVB) while they were bending forward, not rising after bending, and aim to describe the occurrence and the association between bending forward and AVB. METHODS AND RESULTS: In two patients, bending forward was the exclusive trigger for syncope, while in the remaining three, other postural changes (sitting down, standing up, and exertion) could also provoke syncope. Complete AVB as the cause of syncope was documented using ECG monitoring in two cases and an implantable loop recorder in the other three. Ectopic beats without preceding sinus slowing occurred before syncope in four cases. Two cases had a left bundle branch block. All patients responded favourably to cardiac pacing. CONCLUSION: This is the first case series on complete AVB provoked by bending forward. Syncope during bending forward should suggest a search for an AVB. Arguments in favour of a vagal mechanism were syncope triggered by bending forward, and that other triggers could also evoke syncope. However, the absence of sinus slowing before syncope in some cases and the fact that bending forward did not seem to provoke reflex syncope without AVB, cast doubts on a reflex mechanism. There were also arguments favouring conduction disorder: i.e. ectopic beats before syncope and pre-existing conduction disturbances in two cases. The cases are reminiscent of paroxysmal AVB. Discrimination between paroxysmal AVB and vagal AVB is important because a pacemaker is warranted in arrhythmic complete AVB, while the benefit is limited or absent in reflex AVB.

Mechanical extraction of cardiac implantable electronic devices leads with long dwell time: Efficacy and safety of the step up approach.

The aim of this study was to evaluate the efficacy and safety of the stepwise mechanical transvenous lead extraction approach in a patient population with chronically implanted transvenous leads with a long dwell time. From January 2014 till December 2018, all lead extractions with lead dwell time ≥5 years performed at our tertiary centre were retrospectively analysed. A total of 173 leads, from 78 patients (median age 68 years; 81% male) with a median dwell time of 9 years (interquartile range [IQR] 5) were extracted, with three or more leads in 42% of the patients. Right atrial leads: 41%; right ventricular pacing leads: 16%; implantable cardioverter-defibrillator (ICD) leads: 31% (72% dual coil); coronary sinus leads: 12%. The majority (75%) of the leads had an active fixation. Most frequent indication for extraction was pocket infection/erosion (76%). Overall clinical success was 97%, and complete procedural success was 93%. Venous patency, assessed with venous angiography, was well preserved in 93% of the cases. The overall procedural complication rate was 3.8% (2.6% major and 1.3% minor). Despite the complexity of the population and a very long dwell time (median 9 years), a clinical success rate of 97% was achieved with the stepwise mechanical approach. Analysis of impeding progression of pectoral extraction suggests that dense fibrosis and sharp lead curvature in the transvenous trajectory pose a challenge. Complication rate was low, and acute venous patency was generally well preserved.

Assessment of left atrial electro-mechanical delay to predict atrial fibrillation in hypertrophic cardiomyopathy.

AIMS: Atrial fibrillation (AF) is frequently observed in hypertrophic cardiomyopathy (HCM) and is associated with poor clinical outcome. Total atrial conduction time, estimated by tissue Doppler imaging (TDI), the so-called PA-TDI duration, reflects the left atrial (LA) structural and electrical remodelling. The aim of this study was to evaluate the association between PA-TDI and new-onset AF in patients with HCM. METHODS AND RESULTS: From a large cohort of patients with HCM, 208 patients (64% male, mean age 53 ± 14 years) without AF were selected. PA-TDI duration was measured from the onset P wave on electrocardiogram to the peak A' wave of the lateral LA wall using TDI. The incidence of new-onset AF was 20% over a median follow-up of 7.3 (3.5-10.5) years. Patients with incident AF had longer PA-TDI duration when compared with patients without AF (133.7 ± 23.0 vs. 110.5 ± 30.0 ms, P < 0.001). PA-TDI duration was independently associated with new-onset AF (hazard ratio: 1.03, 95% confidence interval: 1.01-1.05, P < 0.001). CONCLUSION: Prolonged PA-TDI duration was independently associated with new-onset AF in patients with HCM. This novel parameter could be useful to risk-stratify patients with HCM who are at risk of having AF.

QT interval variability and heart rate turbulence are associated with clinical characteristics in congenital heart disease patients with a systemic right ventricle.

BACKGROUND: QT interval variability (QTV) and heart rate turbulence (HRT) are measures of cardiac autonomic function, which, when abnormal, are correlated with ventricular arrhythmias and worse clinical outcome. This study aims to evaluate QTV and HRT in patients with a systemic right ventricle (RV) and to assess correlations with clinical characteristics. METHODS: In a retrospective cohort study, QTV and HRT were derived from 24-h Holter registrations of patients with a systemic RV and healthy controls. QTV and HRT were compared between groups. In patients, the association between QTV, HRT, and clinical characteristics was assessed. RESULTS: Holter recordings from 40 patients (mean age 40 years, 16 females) and 37 healthy controls (mean age 42 years, 21 females) were analyzed. Groups were comparable in terms of age and sex. QTV was increased in patients compared with controls (p < 0.001), HRT did not differ significantly between the groups. Increased QTV and decreased HRT correlated with medication use, especially of diuretics, and with clinical events, particularly supraventricular arrhythmias. Increased QTV correlated with reduced systemic RV function. Decreased HRT was independently associated with a larger number of past clinical events (estimate -0.33, 95% CI -0.63 to -0.02, p = 0.037). QTV was higher in women in both patients and controls (p = 0.041 and p = 0.034, respectively). CONCLUSIONS: QTV and HRT are associated with clinical factors and events in patients with a systemic RV. Further studies are mandatory to confirm their prognostic value.

Association between reduced heart rate variability components and supraventricular tachyarrhythmias in patients with a systemic right ventricle.

BACKGROUND: Patients with a systemic right ventricle are prone to develop heart failure. Abnormal heart rate variability (HRV), a measure of autonomic dysfunction, is associated with morbidity and mortality in patients with left ventricular failure. The association between HRV and supraventricular arrhythmias (SVTs), which are associated with adverse events in this population, was assessed. METHODS: 24-Hour Holter recordings of patients with a systemic right ventricle and healthy controls were analysed in a retrospective cohort study. HRV was calculated and compared between groups. Correlation coefficients were determined for HRV variables and clinical characteristics. The relation between HRV and SVTs was investigated with linear regression. RESULTS: The patient group included 29 patients (69%) late after Mustard or Senning correction for transposition of the great arteries, and 13 patients with congenitally corrected transposition of the great arteries (31%). The control group included 38 subjects. HRV was significantly lower in patients compared with controls. In the patient group, lower SDANN (standard deviation of the average NN intervals calculated over 5-minute intervals) was independently associated with a higher number of supraventricular arrhythmias (95% CI -0.03 to -0.0004, p = 0.045). In exploratory correlation analysis, several HRV variables correlated with echocardiographic systemic right ventricular function (rho = 0.36, p = 0.02 for SDANN), and exercise capacity (rho = 0.39, p = 0.05 for SDANN). CONCLUSION: In patients with a systemic right ventricle, HRV is lower compared with controls and (SDANN) is independently associated with supraventricular arrhythmias.

An observational study on survival rates of patients with out-of-hospital cardiac arrest in the Netherlands after improving the 'chain of survival'.

OBJECTIVES: To evaluate the impact of implemented procedures for out-of-hospital cardiac arrests (OHCAs) by determining patient outcome defined as the percentage return of spontaneous circulation at arrival at the emergency department, and 3-month and 1-year-survival rates. DESIGN: Observational study. SETTING: Primary emergency medical care consisting of Advanced Life Support is given by ambulance nurses and secondary care by hospitals within the mid-western part of the Netherlands covering 750 000 inhabitants. PARTICIPANTS: 433 of 500 consecutive patients with OHCA were included in the study over a 1.5 -year period. OUTCOME MEASURES: Analysis included number of patients with return of spontaneous circulation (ROSC) when handed over to the emergency department, survival at 3 months and 1 year including a comparison with global outcome rates. We further considered the influence of gender, delays, bystander Basic Life Support, use of an automated external defibrillator, initial rhythm and mechanical thorax compression in combination with Boussignac tube ventilation. RESULTS: 13% (67/500) of the initial patient population was excluded from the analysis as reanimation in these patients was aborted due to expressed wish not to be resuscitated. Resuscitation was started by bystanders, police and/or first responders in 312/433 (72%) cases. An automated external defibrillator was used in 198 of these 312 cases (63%) of which it defibrillated 108 times. Mechanical thorax compression in combination with Boussignac tube ventilation was necessary in 277/433 patients (64%). Spontaneous circulation returned in 96/277 (35%) patients of this group. In the overall studied population, ROSC percentage at arrival at the hospital was 214/433 (49%). The 3-month and 12-month-survival rates were 123/433 (28%) and 119/433 (27%), respectively. CONCLUSIONS: Optimised 'chain of survival' for patients with OHCA resulted in ROSC in 49% of the cases and a 1-year-survival rate of 27% in the studied population.

Prevalence and Prognostic Implications of Right Ventricular Dysfunction in Patients With Hypertrophic Cardiomyopathy.

Right ventricular (RV) dysfunction is a well-known prognostic factor in several cardiac diseases. However, the prevalence of RV dysfunction in hypertrophic cardiomyopathy (HC) is unclear and its prognostic value is unknown. This study aims at addressing these issues assessing RV function with speckle tracking echocardiography. In 267 HC patients (52 ± 15 years, 68% male), standard and advanced echocardiographic measurements of RV function were performed including RV 4-chamber longitudinal strain (RV4CLS) and RV free wall longitudinal strain (RVFWLS). The primary end point was all-cause mortality and heart failure development. RV dysfunction was observed in 9% of patients based on tricuspid annular plane systolic excursion (≤17 mm), 5% based on fractional area change (<35%), 23% based on RVFWLS ≥-19%, 39% based on RVFWLS ≥-23%, and 55% based on RV4CLS ≥-20%. In total 59 (22%) patients reached the primary end point during a median follow-up of 6.7 (interquartile range 4.2 to 9.8) years. Kaplan-Meier survival curve showed a significant worse survival free of the end point for patients with impaired RV4CLS ≥-20% versus patients with preserved RV4CLS <-20% (log-rank 7.0, p = 0.008) and for patients with impaired RVFWLS ≥-19% versus patients with preserved RVFWLS <-19% (log-rank 4.4, p = 0.037). Multivariable Cox regression analysis showed that E/E' (hazards ratio [HR] 2.26 [1.30 to 3.92], p = 0.004), left ventricular global longitudinal strain LV GLS (HR 1.08 (1.01 to 1.17), p = 0.034) and RV4CLS (HR 1.08 (1.02 to 1.15), p = 0.007) were independently associated with the primary end point. In conclusion, RV dysfunction as measured by longitudinal strain is relatively frequent in HC patients. Impaired RV4CLS is - together with LV GLS and E/E' - associated with adverse outcome, which may indicate a more severe form of HC.