Understanding the incidence of atrial fibrillation and stroke in hypertrophic cardiomyopathy patients: insights from Danish nationwide registries.

AIMS: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors. METHODS AND RESULTS: Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08-1.63], hypertension (HT) (HR 1.36, 95% CI 1.14-1.67), and obstructive HCM (HR 1.27, 95% CI 1.05-1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18-0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis. CONCLUSION: Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC.

Left Ventricular Noncompaction in Childhood: Echocardiographic Follow-Up and Prevalence in First-Degree Relatives.

Background: Left ventricular noncompaction (LVNC) is characterized by excessive trabeculations of the left ventricular (LV) wall. Objectives: The authors aimed to examine changes in LV function and morphology in 2 to 4-year-old children with and without LVNC at birth and to describe the prevalence of LVNC in first-degree relatives. Methods: Echocardiograms in children with and without LVNC (matched 1:4) were performed at 2 to 4 years and in first-degree relatives. LVNC was blindly assessed and defined as a ratio of non-compact to compact myocardium of ≥2 in ≥1 LV segment. Trabeculations were expressed as a percentage of the number of segments with LVNC out of the total number of segments. Results: In total, 14 (median age 3 years, 71% male) of 16 children with LVNC at birth and 56 children without (median age 4 years, 71% male), 37 first-degree relatives of children with LVNC (median age 31 years, 46% male) and 146 first-degree relatives of children without (median age 33 years, 50% male) were included. In children with LVNC, trabeculation (8% vs 13%, P = 0.81) and LV ejection fraction (50% vs 49%, P = 0.91) were unchanged from birth to follow-up but LV ejection fraction was lower compared to children without LVNC (49% vs 60%, P < 0.001). In relatives of children with LVNC, 11 of 37 (30%) fulfilled LVNC criteria compared to no relatives to children without LVNC (P < 0.001). Conclusions: At 2 to 4 years, children with LVNC diagnosed at birth had reduced systolic function compared to children without but did not have progression of LV dysfunction or extent of trabeculations. In first-degree relatives to children with LVNC, 30% fulfilled criteria.

Understanding the incidence of atrial fibrillation and stroke in hypertrophic cardiomyopathy patients: insights from Danish nationwide registries.

AIMS: The treatment of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) can be challenging since AF aggravates symptoms and increases the risk of stroke. Which factors contribute to the development of AF and stroke in HCM remains unknown. The aim of this study was to determine the incidence of AF and stroke in HCM patients and identify the risk factors. METHODS AND RESULTS: Using Danish national registries, all HCM patients from 2005 to 2018 were included. The association between HCM, incident AF, and stroke was investigated using multivariable Cox proportional hazards analysis. Cumulative incidences were calculated using the Aalen-Johansen estimator. Among the 3367 patients without prevalent AF, 24% reached the endpoint of incident AF with death as a competing risk. Median follow-up time was 4 years. Atrial fibrillation incidence was equal between sexes and increased for patients with ischaemic heart disease [IHD; hazard ratio (HR) 1.33, 95% confidence interval (CI) 1.08-1.63], hypertension (HT) (HR 1.36, 95% CI 1.14-1.67), and obstructive HCM (HR 1.27, 95% CI 1.05-1.52). Seven per cent developed stroke, with no difference detected stratifying for the presence of AF. Sub-analysis revealed that when AF was treated with oral anticoagulants (OACs), stroke was less likely (HR 0.4, 95% CI 0.18-0.86, P = 0.02). However, 34% of patients were not receiving adequate anticoagulation following AF diagnosis. CONCLUSION: Obstructive HCM, HT, and IHD were associated with increased risk of AF. Prevalent AF alone was not predictive of stroke; however, AF patients treated with OAC were significantly less likely to develop stroke, suggesting that this development is driven by the protective effect of OAC. Despite this, 34% of patients did not receive OAC.

Natural history of cardiac involvement in myotonic dystrophy type 1 - Emphasis on the need for lifelong follow-up.

BACKGROUND: Cardiac involvement represents a major cause of morbidity and mortality in patients with myotonic dystrophy type 1 (DM1) and prevention of sudden cardiac death (SCD) is a central part of patient care. We investigated the natural history of cardiac involvement in patients with DM1 to provide an evidence-based foundation for adjustment of follow-up protocols. METHODS: Patients with genetically confirmed DM1 were identified. Data on patient characteristics, performed investigations (12 lead ECG, Holter monitoring and echocardiography), and clinical outcomes were retrospectively collected from electronic health records. RESULTS: We included 195 patients (52% men) with a mean age at baseline evaluation of 41 years (range 14-79). The overall prevalence of cardiac involvement increased from 42% to 66% after a median follow-up of 10.5 years. There was a male predominance for cardiac involvement at end of follow-up (74 vs. 44%, p < 0.001). The most common types of cardiac involvement were conduction abnormalities (48%), arrhythmias (35%), and left ventricular systolic dysfunction (21%). Only 17% of patients reported cardiac symptoms. The standard 12­lead ECG was the most sensitive diagnostic modality and documented cardiac involvement in 24% at baseline and in 49% at latest follow-up. However, addition of Holter monitoring and echocardiography significantly increased the diagnostic yield with 18 and 13% points at baseline and latest follow-up, respectively. Despite surveillance 35 patients (18%) died during follow-up; seven due to SCD. CONCLUSIONS: In patients with DM1 cardiac involvement was highly prevalent and developed during follow-up. These findings justify lifelong follow-up with ECG, Holter, and echocardiography. CLINICAL PERSPECTIVE: What is new? What are the clinical implications?

The Impact of Maternal and Perinatal Factors on the Neonatal Electrocardiogram.

INTRODUCTION: Myocardial development is still transitioning by the time of birth making the cardiomyocyte vulnerable to maternal and perinatal factors. We aimed at investigating the impact of maternal and perinatal factors on the neonatal electrocardiogram. METHODS: In a prospective cohort study, neonates underwent cardiac evaluation with electrocardiograms and echocardiograms (age 0-30 days). Associations between medical and demographic data, pregnancy, and birth-related factors, and electrocardiographic parameters were assessed. RESULTS: A total of 15,928 singletons with normal echocardiograms were included (52% boys). Neonates were divided into groups by accumulated number of maternal/perinatal factors: 0, 1, 2, 3, 4, and ≥5, and between-group differences in electrocardiographic parameters were analysed. We observed an additive effect with a leftward shift of the QRS axis and QT prolongation (all p < 0.01). Comparing extreme groups (0 vs. ≥5 maternal/perinatal factors), we found a 4.3% more left-shifted QRS axis (117 vs. 112°, p < 0.001) and a 0.8% prolonged QTcFridericia (QTcF; 363 vs. 366 ms, p < 0.001); the effect on QTcF was most pronounced in neonates examined in the first week of life (360 vs. 368 ms, p < 0.0001). CONCLUSION: We observed a cumulative effect of maternal and perinatal factors on neonatal electrocardiographic parameters, including a more left-shifted QRS axis and increased QT duration, although the variation was within normal reference ranges. Our findings add to the knowledge on the neonatal cardiac transition and the cardiac effect of maternal/perinatal factors.

High risk of ischaemic stroke amongst patients with hereditary haemorrhagic telangiectasia.

BACKGROUND AND PURPOSE: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disease with fragile blood vessels and vascular malformations, potentially causing neurological manifestations, including stroke and cerebral abscesses. The study aimed to investigate neurological manifestations in the Danish HHT database, focusing on pulmonary arteriovenous malformations (PAVMs) as a risk factor for cerebral events. METHODS: Retrospective analysis of the Danish HHT database was conducted, cross-referencing neurological outcomes with the Danish Apoplexy Register for accuracy. Patients were stratified by HHT type. Primary outcomes included ischaemic stroke, transient ischaemic attack and cerebral haemorrhage. Secondary outcomes comprised age, age at HHT diagnosis, age at cerebral ischaemic event, and PAVM and cerebral arteriovenous malformation status. RESULTS: Six hundred and sixty-four HHT patients were included. PAVM was diagnosed in 54% of patients, with higher prevalence in HHT type 1 (70%) compared to HHT type 2 (34%) and juvenile polyposis HHT (66%). Ischaemic stroke or transient ischaemic attack occurred in 12.5%, with a higher risk associated with macroscopic PAVM. Logistic regression showed a nearly 10 times increased risk of ischaemic stroke with macroscopic PAVM. Cerebral abscesses occurred in 3.2% of patients, all with macroscopic PAVM. Incomplete PAVM closure increased cerebral abscess risk. CONCLUSION: This study provides valuable insights into the prevalence of neurological manifestations and vascular events in HHT patients. The presence of PAVM was associated with an increased risk of ischaemic stroke, highlighting the importance of early screening and intervention. The findings emphasize the need for comprehensive management strategies targeting both vascular and neurological complications in HHT patients, especially regarding secondary stroke prevention.

Aortic dissection in a young male with persistent ductus arteriosus and a novel variant in MYLK.

Pathogenic variants in several genes involved in the function or regulation of smooth muscle cells (SMC) are known to predispose to congenital heart disease and thoracic aortic aneurysm and dissection (TAAD). Variants in MYLK are primarily known to predispose to TAAD, but a growing body of evidence points toward MYLK also playing an essential role in the regulation of SMC contraction outside the aorta. In this case report, we present a patient with co-occurrence of persistent ductus arteriosus (PDA) and thoracic aortic dissection. Genetic analyses revealed a novel splice acceptor variant (c.3986-1G > A) in MYLK, which segregated with disease in the family. RNA-analyses on fibroblasts showed that the variant induced skipping of exon 24, which resulted in an in-frame deletion of 101 amino acids. These findings suggest that MYLK-associated disease could include a broader phenotypic spectrum than isolated TAAD, including PDA and obstructive pulmonary disease. Genetic analyses could be considered in families with TAAD and PDA or obstructive pulmonary disease.

Electrocardiographic Characteristics in 438 Neonates with Atrial Septal Defects.

Arrhythmias and electrocardiographic (ECG) abnormalities are common among patients with atrial septal defects (ASDs). We studied a large cohort of neonates with ASDs to investigate whether ECG abnormalities are present at this early stage or develop later, secondary to hemodynamic changes. We analyzed the echocardiograms and ECGs from the Copenhagen Baby Heart Study, a population-based cohort study. We compared ECG characteristics of 438 neonates with secundum ASDs to 1314 matched controls. In subgroup analyses, we investigated whether electrocardiographic characteristics were associated with age at examination. Neonates with ASDs (median age, 11 days; males, 51%) had longer P-wave durations (58 vs. 56 ms, p < 0.001), PR intervals (100 vs. 96 ms, p < 0.001), and a more rightward-shifted QRS axis (116 vs. 114 degrees, p = 0.032) compared to controls (median age, 10 days; males, 51%). There were no differences between cases and controls in the P-wave area, amplitude, or axis. Subgroup analyses showed that the differences in P-wave duration and PR interval were present in neonates examined in the first week after birth. The difference in the QRS axis was not found in neonates examined this early but was found in neonates examined at age two to four weeks. In conclusion, ASDs are associated with ECG changes from the neonatal phase. The P-wave duration and PR interval are longer in neonates with ASDs when compared to controls as early as the first week after birth, indicating that these changes are not purely secondary, but that neonates with an ASD have altered cardiac electrical activity.ClinicalTrials.gov Identifier NCT02753348 (April 27, 2016).

Skeletal Muscle Involvement in Patients With Truncations of Titin and Familial Dilated Cardiomyopathy.

BACKGROUND: Genetic variants in titin (TTN) are associated with dilated cardiomyopathy (DCM) and skeletal myopathy. However, the skeletal muscle phenotype in individuals carrying heterozygous truncating TTN variants (TTNtv), the leading cause of DCM, is understudied. OBJECTIVES: This study aimed to assess the skeletal muscle phenotype associated with TTNtv. METHODS: Participants with TTNtv were included in a cross-sectional study. Skeletal muscle fat fraction was evaluated by magnetic resonance imaging (compared with healthy controls and controls with non-TTNtv DCM). Muscle strength was evaluated by dynamometry and muscle biopsy specimens were analyzed. RESULTS: Twenty-five TTNtv participants (11 women, mean age 51 ± 15 years, left ventricular ejection fraction 45% ± 10%) were included (19 had DCM). Compared to healthy controls (n = 25), fat fraction was higher in calf (12.5% vs 9.9%, P = 0.013), thigh (12.2% vs 9.3%, P = 0.004), and paraspinal muscles (18.8% vs 13.9%, P = 0.008) of TTNtv participants. Linear mixed effects modelling found higher fat fractions in TTNtv participants compared to healthy controls (2.5%; 95% CI: 1.4-3.7; P < 0.001) and controls with non-TTNtv genetic DCM (n = 7) (1.5%; 95% CI: 0.2-2.8; P = 0.025). Muscle strength was within 1 SD of normal values. Biopsy specimens from 21 participants found myopathic features in 13 (62%), including central nuclei. Electron microscopy showed well-ordered Z-lines and T-tubuli but uneven and discontinuous M-lines and excessive glycogen depositions flanked by autophagosomes, lysosomes, and abnormal mitochondria with mitophagy. CONCLUSIONS: Mild skeletal muscle involvement was prevalent in patients with TTNtv. The phenotype was characterized by an increased muscle fat fraction and excessive accumulation of glycogen, possibly due to reduced autophagic flux. These findings indicate an impact of TTNtv beyond the heart.

The Neonatal QRS Complex and Its Association with Left Ventricular Mass.

To evaluate QRS complex features during the first month of life and the association with echocardiographic measurements of left ventricular mass in neonates. Prospective cohort study of neonates with electrocardiography (ECG) and echocardiography performed during the first month of life. Left ventricular mass index (LVMI) was determined by echocardiography and the correlation with electrocardiographic markers of LVMI outliers (≥ 98th percentile) were analyzed. We included 17,450 neonates (52% boys; median age at examination 11 days) and found an increase in median QRS duration and LVMI during the first month of life (54 vs. 56 ms and 24.7 vs. 28.6 g/m2 at days 0-4 and 25-30, respectively; both p < 0.001). All investigated ECG features (QRS duration, QRS area in V1/V6, maximum amplitudes of S-V1/R-V6, and the Sokolow-Lyon voltage product) showed no to low correlation with LVMI, resulting in low sensitivities (0-9.0%), but high specificities (97.2-98.1%), and area under the curve values close to the identity line (0.49-0.61) for identifying LVMI outliers. Adjustment of outlier definition for LVMI and threshold for QRS features had no significant effect on sensitivity. We present reference values for QRS complex features and their association with LVMI in neonates from a large, unselected, population-based cohort. The QRS complex gradually evolved during the first month of life but had a low correlation with LVMI. Our results indicate a poor diagnostic value of using ECG features to identify LVMI outliers in neonates.Trial Registry Copenhagen Baby Heart, NCT02753348, https://clinicaltri-als.gov/ct2/show/NCT02753348?cond=Copenhagen+Baby+Heart&draw=2&rank=1 , deidentified individual participant data will not be made available.

Causes of death among non-urgent patients in the emergency department who die within 30 days.

INTRODUCTION: Patients triaged as non-urgent in the emergency department constitute a diverse group with a low mortality rate assumed to be able to wait three hours for a physician. Little is known about the causes of death of non-urgent patients who die shortly after admission. We examined whether deaths among non-urgent patients were preventable. METHOD: Using data from the Copenhagen Triage Algorithm Study, we conducted a review of electronic medical records of all patients triaged as non-urgent who died within 30 days of presentation and constructed short summaries. These summaries were reviewed by two senior physicians who determined whether each death was expected or unexpected. The unexpected deaths were further assessed as unrelated or related to admission and if related as preventable or unpreventable. Any disagreements were settled by a third senior physician. RESULTS: Among the patients triaged as non-urgent, 335 of 14,655 (2%) died within 30 days. When comparing biomarkers and age, the non-urgent patients resembled the patients in other triage categories who died within 30 days. Most deaths were expected or not preventable (96%). The preventable deaths (n = 13, 4%) were among older patients with comorbidities. Causes of death were sudden cardiac arrest (n = 3), infection (n = 4), kidney failure (n = 1), electrolyte derangement (n = 1) and unknown (n = 4). CONCLUSION: Preventable deaths among non-urgent patients were rare and no overrepresentation was observed of specialties or diseases. FUNDING: Trygfonden. CLINICALTRIALS: gov:NCT02698319.

Remote Ischemic Conditioning for Acute Stroke: The RESIST Randomized Clinical Trial.

Importance: Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke. Objective: To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke. Design, Setting, and Participants: This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023). Intervention: The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants. Main Outcomes and Measures: The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke. Results: Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, -1; -1.7 to -0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group. Conclusions and Relevance: RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke. Trial Registration: ClinicalTrials.gov Identifier: NCT03481777.

Complex effects of sequence variants on lipid levels and coronary artery disease.

Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions. These complex effects can translate into CAD risk. For example, Trp154Ter in FUT2 protects against CAD among subjects with the A1 blood group, whereas it associates with greater risk of CAD in others. His48Arg in ADH1B interacts with alcohol consumption to affect lipid levels and CAD. The effect of variants in TM6SF2 on blood lipids is greatest among those who never eat oily fish but absent from those who often do. This work demonstrates that variants that affect variance of quantitative traits can allow for the discovery of epistasis and interactions of variants with the environment.

Electrocardiographic characteristics of newborns with ventricular septal defects: a Copenhagen Baby Heart Study.

Ventricular septal defects (VSD) represent the most common congenital heart defect in newborns. We assessed the electrocardiographic characteristics of newborns with VSDs in a general population sample. The Copenhagen Baby Heart Study is a prospective population-based cohort study offering cardiac evaluation of newborns. Echocardiograms and electrocardiograms were obtained within 30 days after birth and systematically analysed. A VSD was identified in 530 newborns (mean age 11 ± 7 days, 42% boys). Newborns with VSDs had a more left-shifted QRS axis (116 ± 34 vs. 120 ± 3°, p = 0.02), and a higher S-wave amplitude in V1 (721 ± 584 vs. 636 ± 549 µV, p = 0.001) than controls. The largest differences were found in newborns with large or perimembraneous VSDs with a higher frequency of left axis deviation, higher S-wave amplitudes in V1, and higher R- and S-wave amplitudes in V6 compared with controls. R-waves in V1 and V6 were significantly associated to left ventricular mass, whereas S-waves in V1 and V6 were dependent on left ventricular end-diastolic diameter on echocardiography.  Conclusion: Newborns with VSDs showed significant differences in QRS axis, and R- and S-wave precordial amplitudes compared to matched controls. Perimembranous and large VSDs had the greatest effect on the neonatal ECG. What is Known: • Ventricular septal defects in newborns are prevalent and may affect cardiac function and structure. What is New: • The Copenhagen Baby Heart Study is the largest study including a cohort of unselected newborns undergoing postnatal cardiac examination. • We found that newborns with VSD showed significant electrocardiographic differences depending on size and type of VSD compared with healthy newborns.

The Novel Familial ST-Depression Syndrome - Current Knowledge and Perspectives.

Familial ST-depression syndrome represents a novel inherited disease characterized by nonischemic ST-segment depressions in multiple leads. The ECG phenotype appears to debut around puberty, while the typical onset of arrhythmias occurs around 50 years of age. Clinical manifestations include supraventricular arrhythmias, fast polymorphic ventricular tachycardia, sudden cardiac death, and left ventricular systolic dysfunction. The optimal treatment is unknown but asymptomatic individuals without red flags may not need treatment. In contrast, ICD implantation should be considered in patients with probable arrhythmic syncope and in those fulfilling general criteria for ICD treatment. Future research should focus on establishing the disease prevalence, optimizing risk stratification and treatment, and elucidating the underlying genetic etiology.

A Systematic Analysis of the Clinical Outcome Associated with Multiple Reclassified Desmosomal Gene Variants in Arrhythmogenic Right Ventricular Cardiomyopathy Patients.

The presence of multiple pathogenic variants in desmosomal genes (DSC2, DSG2, DSP, JUP, and PKP2) in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) has been linked to a severe phenotype. However, the pathogenicity of variants is reclassified frequently, which may result in a changed clinical risk prediction. Here, we present the collection, reclassification, and clinical outcome correlation for the largest series of ARVC patients carrying multiple desmosomal pathogenic variants to date (n = 331). After reclassification, only 29% of patients remained carriers of two (likely) pathogenic variants. They reached the composite endpoint (ventricular arrhythmias, heart failure, and death) significantly earlier than patients with one or no remaining reclassified variant (hazard ratios of 1.9 and 1.8, respectively). Periodic reclassification of variants contributes to more accurate risk stratification and subsequent clinical management strategy. Graphical Abstract.

The Wolff-Parkinson-White pattern in neonates: results from a large population-based cohort study.

AIMS: Wolff-Parkinson-White (WPW) syndrome is a conduction disorder characterized by an accessory electrical pathway between the atria and ventricles, which may predispose to supraventricular tachycardia (SVT) and sudden cardiac death. It can be seen as an isolated finding or associated with structural heart disease. Our aims were to determine the prevalence of a WPW pattern in a large and unselected cohort of neonates and to describe the electro- and echocardiographic characteristics as well as the natural history during early childhood. METHODS AND RESULTS: Electrocardiograms and echocardiograms of neonates (aged 0-30 days) from a large, prospective, population-based cohort study were included. Neonates with a WPW pattern were identified and matched 1:4 to controls. Localization of the accessory pathway was assessed by different algorithms. Among 17 489 neonates, we identified 17 (76% boys) with a WPW pattern consistent with a prevalence of 0.1%. One neonate had moderate mitral regurgitation while other echocardiographic parameters were similar between cases and controls (all P > 0.05). The accessory pathways were primarily predicted to be left-sided. At follow-up (available in 14/17 children; mean age 3.2 years) the pre-excitation pattern persisted in only four of the children and none of the children had experienced any episodes of SVT. CONCLUSION: The prevalence of a WPW pattern in our cohort of unselected neonates was 0.1%. The WPW pattern was more frequent in boys and generally not associated with structural heart disease, and the accessory pathways were primarily left-sided. At follow-up, the WPW pattern had disappeared in most of the children suggesting either an intermittent nature or that normalization occurs. CLINICAL TRIAL REGISTRATION: Copenhagen Baby Heart, NCT02753348.

CineECG analysis provides new insights into Familial ST-segment Depression Syndrome.

AIMS: Familial ST-segment Depression Syndrome (Fam-STD) is a novel inherited cardiac disease associated with arrhythmias and sudden cardiac death. This study aimed at investigating the cardiac activation pathway in patients with Fam-STD, modelling the electrocardiogram (ECG) phenotype, and performing in-depth ST-segment analyses. METHODS AND RESULTS: CineECG analysis of patients with Fam-STD and age- and sex-matched controls. The groups were compared using the CineECG software which included the trans-cardiac ratio and the electrical activation pathway. We simulated the Fam-STD ECG phenotype by adjusting action potential duration (APD) and action potential amplitude (APA) in specific cardiac regions. High-resolution ST-segment analyses were performed per lead by dividing the ST-segment into nine 10 ms subintervals. Twenty-seven Fam-STD patients (74% females, mean age 51.6 ± 6.2 years) and 83 matched controls were included. Among Fam-STD patients, electrical activation pathway analysis in the anterior-basal orientation showed significantly abnormal direction toward the basal areas of the heart starting from QRS 60-89 ms until Tpeak-Tend (all P < 0.001). Simulations with shortened APD and reduced APA in the left ventricle basal regions recapitulated the Fam-STD ECG phenotype. Detailed ST-segment analyses showed significant differences in all nine 10 ms subintervals (all P < 0.01), with the most prominent findings during the 70-79/80-89 ms intervals. CONCLUSION: CineECG analyses indicated abnormal repolarization with basal directions, and the Fam-STD ECG phenotype was simulated by reducing APD and APA in the left ventricle basal regions. Detailed ST-analysis showed amplitudes consistent with the proposed diagnostic criteria for Fam-STD patients. Our findings provide new insight into the electrophysiological abnormalities of Fam-STD.