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Biomedical subjects

Jesper Hastrup Svendsen

Publications and source records attributed to Jesper Hastrup Svendsen.

18 recordsLinked to original sources

Genome-Wide Association Study of Accessory Atrioventricular Pathways.

IMPORTANCE: Understanding of the genetics of accessory atrioventricular pathways (APs) and affiliated arrhythmias is limited. OBJECTIVE: To investigate the genetics of APs and affiliated arrhythmias. DESIGN, SETTING, AND PARTICIPANTS: This was a genome-wide association study (GWAS) of APs, defined by International Classification of Diseases (ICD) codes and/or confirmed by electrophysiology (EP) study. Genome-wide significant AP variants were tested for association with AP-affiliated arrhythmias: paroxysmal supraventricular tachycardia (PSVT), atrial fibrillation (AF), ventricular tachycardia, and cardiac arrest. AP variants were also tested in data on other heart diseases and measures of cardiac physiology. Individuals with APs and control individuals from Iceland (deCODE Genetics), Denmark (Copenhagen Hospital Biobank, Danish Blood Donor Study, and SupraGen/the Danish General Suburban Population Study [GESUS]), the US (Intermountain Healthcare), and the United Kingdom (UK Biobank) were included. Time of phenotype data collection ranged from January 1983 to December 2022. Data were analyzed from August 2022 to January 2024. EXPOSURES: Sequence variants. MAIN OUTCOMES AND MEASURES: Genome-wide significant association of sequence variants with APs. RESULTS: The GWAS included 2310 individuals with APs (median [IQR] age, 43 [28-57] years; 1252 [54.2%] male and 1058 [45.8%] female) and 1 206 977 control individuals (median [IQR] year of birth, 1955 [1945-1970]; 632 888 [52.4%] female and 574 089 [47.6%] male). Of the individuals with APs, 909 had been confirmed in EP study. Three common missense variants were associated with APs, in the genes CCDC141 (p.Arg935Trp: adjusted odds ratio [aOR], 1.37; 95% CI, 1.24-1.52, and p.Ala141Val: aOR, 1.55; 95% CI 1.34-1.80) and SCN10A (p.Ala1073Val: OR, 1.22; 95% CI, 1.15-1.30). The 3 variants associated with PSVT and the SCN10A variant associated with AF, supporting an effect on AP-affiliated arrhythmias. All 3 AP risk alleles were associated with higher heart rate and shorter PR interval, and have reported associations with chronotropic response. CONCLUSIONS AND RELEVANCE: Associations were found between sequence variants and APs that were also associated with risk of PSVT, and thus likely atrioventricular reentrant tachycardia, but had allele-specific associations with AF and conduction disorders. Genetic variation in the modulation of heart rate, chronotropic response, and atrial or atrioventricular node conduction velocity may play a role in the risk of AP-affiliated arrhythmias. Further research into CCDC141 could provide insights for antiarrhythmic therapeutic targeting in the presence of an AP.

Humans↗

[Long QT syndrome--genes, mechanisms and risks. Indication for genetic family screening?].

Inherited long QT syndrome (LQTS) is a cardiac disease characterised by episodes of ventricular tachyarrhythmia, presenting as syncope or sudden death. Untreated, the annual mortality rate is 1-2%. Sudden death has been reported as the first manifestation of the disease in some cases. Therefore, early (pre-symptomatic) diagnosis and management may save lives. However, clinically false negative relatives are also at risk of sudden death. On this basis we conclude assessment of relatives should be extended with genetic testing.

Death, Sudden, Cardiac↗

Atrial secretion of B-type natriuretic peptide.

In the normal heart, the endocrine capacity resides in the atria. Atrial myocytes express and secrete natriuretic hormones that regulate fluid homeostasis and blood pressure. But in ventricular disease, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) gene expression is also activated in ventricular myocytes. Plasma concentrations of natriuretic peptides and their biosynthetic precursors are accordingly increased in patients with marked ventricular dysfunction. In contrast, atrial peptide secretion in ventricular disease has received less attention, and our present understanding of the endocrine atria during ventricular dysfunction is still scarce. Although ventricular disease and increased circulating concentrations are associated, it does not entail that the ventricle is the sole or even the main source in all types of heart disease. Clearly, the endocrine atria are also active in heart failure. Plasma measurement of cardiac natriuretic peptides and their molecular precursors can perhaps help us to discriminate when, where and how.

Atrial Fibrillation↗

Atrial and ventricular volume and function evaluated by magnetic resonance imaging in patients with persistent atrial fibrillation before and after cardioversion.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and 25% of those >40 years old will experience AF. Left atrial size and left ventricular function are independently related to cardiovascular morbidity and mortality. Our aim was to evaluate cardiac volume and function using magnetic resonance imaging in patients with persistent AF and to describe the changes after cardioversion (CV). Sixty consecutive patients with persistent AF and 19 healthy volunteers had cardiac volumes evaluated by cinematographic breath-hold magnetic resonance imaging. Patients with AF were evaluated before CV and at 1, 30, and 180 days after CV, if still in sinus rhythm. All atrial and ventricular volumes and left ventricular mass decreased and ejection fractions increased significantly after CV (p <0.0001 for all variables). Atrial and ventricular diastolic volumes increased significantly the day after CV. The atrial diastolic volumes had decreased significantly at 30 days and ventricular volumes at 180 days. The atrial systolic volumes decreased significantly the day after CV, but the ventricular systolic volumes remained constant the day after CV and decreased thereafter. Only the right atrial volumes were normalized 180 days after CV. The same results were found in a subgroup of patients with lone AF. In conclusion, reversal of atrial dimensions and function happened earlier than ventricular reversal after CV in persistent AF. Atrial reversal began immediately and ventricular reversal was not seen before 30 days after CV. Our results suggest that the changes to the left atrium and both ventricles caused by AF could be permanent and that CV of AF may be preferable.

Adult↗

The effectiveness of a high output/short duration radiofrequency current application technique in segmental pulmonary vein isolation for atrial fibrillation.

AIMS: Segmental pulmonary vein (PV) isolation by radiofrequency (RF) catheter ablation has become a curative therapy for atrial fibrillation (AF). However, the long procedure time limits the wide application of this procedure. The aim of the current study was to compare a novel ablation technique with a high power output and short application time vs. a conventional technique using a low power output and long application time. METHODS AND RESULTS: The study included 90 consecutive patients (age 53+/-10 years; 66 men). Segmental PV isolation was performed by irrigated RF catheter ablation in both groups. In the conventional group (Group 1, 45 patients), the power output was limited to 30 W with a target temperature of 50 degrees C and an RF preset duration of 120 s. In the novel group (Group 2, 45 patients), the maximum power output was preset to 45 W, with a target temperature of 55 degrees C and duration of 20 s. In Group 2, a significant reduction in the PV isolation time (127+/-57 vs. 94+/-33 min, P<0.02), mean fluoroscopy time (73+/-23 vs. 55+/-16 min, P<0.001), and radiation dose was observed. According to the application time and number, Group 2 showed a reduction in RF application time, but a higher number of RF applications were required for creation of complete PV isolation. During a mean follow-up of 15+/-7 months, a total of 74% of patients in Group 1 and 76% of patients in Group 2 demonstrated stable SR. CONCLUSION: Segmental PV isolation using a high power output and short application time is safe and effective in PV isolation in patients with AF. This technique can significantly reduce the procedure and fluoroscopy time compared with a low-power output technique.

Atrial Fibrillation↗

Indication of the radiofrequency induced lesion size by pre-ablation measurements.

BACKGROUND: During radiofrequency ablation of arrhythmias tissue heating and hence lesion size depend on electrode-tissue contact and cooling of the electrode tip caused by cavitary blood flow. These factors are unique and unknown for each catheter placement in the beating heart. A tool for assessing these factors prior to ablation may indicate the lesion size which will be obtained for any given catheter position. METHODS AND RESULTS: Radiofrequency ablation was performed in vitro on strips of left ventricular porcine myocardium during two different levels of convective cooling (0 or 0.1 m/s), two different contact pressures (10 or 30 g) and parallel or perpendicular electrode-tissue orientation using 7F 4 mm tip catheters. Prior to ablation the impedance rise (DeltaIMP) caused by the obtained contact and the temperature rise with a 0.6 W 5 s test pulse (DeltaT) were measured. Subsequently, during unchanged conditions, radiofrequency ablation was performed as either temperature-controlled, power-controlled or irrigated tip ablation and lesion size was determined. DeltaIMP increased significantly (P < 0.05) by improved contact, whereas it was not affected by convective cooling. DeltaT was significantly increased by increasing contact pressure (P < 0.05) and significantly decreased by increased cooling (P < 0.001). DeltaT was not systematically affected by electrode orientation. The product of DeltaT and DeltaIMP showed a significant correlation between the obtained lesion size and power output for temperature-controlled and between lesion size and tip temperature for power-controlled ablation (P < 0.001). CONCLUSIONS: Pre-ablation measurement of DeltaIMP and DeltaT can indicate the lesion size resulting after ablation in temperature-controlled, power-controlled and irrigated ablation in vitro, since DeltaT reflects cavitary cooling and to a smaller extent electrode-tissue contact, and DeltaIMP reflects only electrode-tissue contact.

Animals↗

[Dynamic ECG changes as a result of Brugada syndrome, an overlooked diagnosis?].

Brugada syndrome is a primary electrical disease involving a wide spectrum of phenotypes. The hallmark of Brugada syndrome is the ST elevation in leads V1 to V3. We present three cases of Brugada syndrome. The first patient was diagnosed via routine ECG and a programmed electric stimulation. The second patient was mistakenly diagnosed as having a right coronary occlusion. The last patient had been resuscitated before admittance and received an implantable cardioverter-defibrillator. Treatment of patients with Brugada syndrome is limited by the lack of reliable indicators of risk.

Adult↗

Relation of 97T polymorphism in KCNE5 to risk of atrial fibrillation.

The 97T polymorphism of the KCNE5 gene, coding for an inhibitory beta-subunit, MiRP4, of the repolarizing cardiac potassium ion channel KCNQ1, was significantly more frequent in 96 controls than in 158 patients with atrial fibrillation (AF). KCNQ1 is involved in cardiac action potential, and increased function has been associated with AF. Because the KCNE5 gene is located on the X chromosome, the protection conferred by the 97T polymorphism may help explain the gender-related difference in the risk of AF.

Adult↗

Inflammation in the genesis and perpetuation of atrial fibrillation.

The prevalence and persistence of atrial fibrillation (AF) and the relative inefficacy of the currently available pharmacotherapy requires development of new treatment strategies. Recent findings have suggested a mechanistic link between inflammatory processes and the development of AF. Epidemiological studies have shown an association between C-reactive protein and both the presence of AF and the risk of developing future AF. In case-control studies, C-reactive protein is significantly elevated in AF patients and is associated with successful cardioversion. Moreover, C-reactive protein elevation is more pronounced in patients with persistent AF than in those with paroxysmal AF. Furthermore, treatment with glucocorticoids, statins, angiotensin converting enzyme inhibitors, and angiotensin II receptor blockers seems to reduce recurrence of AF. Part of this anti-arrhythmic effect may be through anti-inflammatory activity. This article reviews what is known about inflammation in genesis and perpetuation of AF, the putative underlying mechanisms, and possible therapeutic implications for the inhibition of inflammation as an evolving treatment modality for AF.

Atrial Fibrillation↗

Increased resting heart rate following radiofrequency catheter ablation for atrial fibrillation.

AIM: Sinus tachycardia has been observed following radiofrequency (RF) catheter ablation for various kinds of supraventricular tachycardia. This study is aimed at determining the occurrence of changes in sinus-rhythm heart rate (HR) after pulmonary vein (PV) isolation in patients with paroxysmal/persistent atrial fibrillation (AF), prospectively. METHODS: Patients with a history of AF underwent segmental or circumferential isolation of the PVs. A total of 62 consecutive patients, mean age 55 +/- 10, was included. Clinical evaluation was performed before and one, three, six, nine, and 12 months following the procedure. RESULTS: Following PV isolation, the mean HR significantly increased from 58 +/- 10 bpm at baseline to 67 +/- 12 bpm at one month, 71 +/- 13 bpm at three months, 69 +/- 12 bpm at six months, 69 +/- 13 at nine months, and 70 +/- 13 at 12 months follow-up. The ablation success significantly correlated with the increase in HR at one month follow-up. In three patients the mean HR increased > 25 bpm resulting in symptoms necessitating therapy with rate-controlling drugs. CONCLUSION: PV isolation in patients with AF may result in increased HR, which positively correlated with the ablation success. This change does not seem to resolve spontaneously after a follow-up of 12 months. Approximately 5% of patients may develop symptoms due to an increased HR, necessitating treatment with rate-controlling drugs.

Atrial Fibrillation↗

Atrial and ventricular volume and function in persistent and permanent atrial fibrillation, a magnetic resonance imaging study.

Left atrial size is independently related to cardiovascular morbidity and mortality, and atrial fibrillation (AF) is strongly associated with atrial size. Our aims were to report atrial and ventricular dimensions in patients with AF evaluated with magnetic resonance imaging (MRI), and to assess the inter-study reproducibility of the measurements. Nineteen healthy volunteers, 19 patients with permanent AF, and 58 patients with persistent AF had cardiac dimensions evaluated by 6-mm cinematographic breath-hold MRI scans using a 1.5 Tesla Siemens Vision Magnetom scanner with a phased array chest coil. Intraobserver variability and inter-study reproducibility of the cardiac volumes and ejection fractions (EF) gave acceptable Bland-Altman plots, good correlations (R2: 0.80-0.99), and low reproducibility coefficients. The mean atrial volumes were similar in the two groups with AF [systolic vol. index (SVI): 75.9-80.3 mL/m2; diastolic vol. index (DVI): 77.4-82.1 mL/m2] and significantly different from the healthy volunteers (SVI: 30.3 mL/m2; DVI: 62.3 mL/m2; p < 0.0001). Mean left ventricular (LV) volumes and EF were significantly different in permanent AF (SVI: 34.2 mL/m2; DVI: 68.3 mL/m2; EF: 50.8%) compared to persistent AF [SVI: 44.0 mL/m2 (p = 0.02); DVI: 77.2 mL/m2 (p = 0.03); EF: 44.9% (p = 0.02)], and closer to the normal values (SVI: 22.4 mL/m2; DVI: 66.5 mL/m2; EF: 67.0%). MRI is a highly reproducible method for measurement of atrial and ventricular dimensions in healthy volunteers and in patients with AF. Our results suggest that atrial dilatation appears within the first months of AF and stays more or less unchanged thereafter. The LV appears to dilate early as a response to AF, but later seems to adapt.

Adult↗

Acute fatal pulmonary vein occlusion after catheter ablation of atrial fibrillation.

BACKGROUND: In treatment of atrial fibrillation (AF) catheter radiofrequency isolation of the pulmonary veins (PVs) has proved to be highly successful. There have been several case reports regarding PV stenosis, however none of these have reported a fatal outcome. METHODS AND RESULTS: A 31-year-old man was referred to us for treatment of complications related to catheter ablation. According to the documentation from the hospital, the patient underwent segmental ostial PV isolation for treatment of AF. A few hours after the procedure, the patient developed dyspnoea, hemoptysis, and a high fever. The patient was first diagnosed as having pneumonia but five days later transesophageal echocardiography and pulmonal angiography revealed total occlusion of the left superior and inferior PVs. When we received the patient he underwent open-heart surgery, which showed thrombi in the orifices of the left sided PVs protruding into the left atrium. In each of the left sided PVs severe stenosis was seen in the bifurcation area. Thrombus material was removed followed by placement of two stents in each of the left sided pulmonary veins at the first bifurcations. However, the patient died 14 days after the ablation procedure. Selective autopsy of the left lung revealed diffuse alveolar damage, disseminated intravascular coagulation, multiple thrombi formation, and haemorrhagic infarctions. CONCLUSIONS: PV stenosis may occur very early after the ablation procedure. Delayed diagnosis can be fatal. The early stenosis may result in thrombus formation in the left atrium and PVs and in this case surgery should be considered.

Adult↗

Mechanisms for enlarging lesion size during irrigated tip radiofrequency ablation: is there a virtual electrode effect?

INTRODUCTION: Irrigated tip radiofrequency ablation of cardiac arrhythmias was developed to increase the size of the radiofrequency-induced lesion, since cooling of the electrode tip allows use of higher power settings. The purpose of this study was to determine if the increased lesion size during irrigated tip ablation is caused by the cooling effect solely or if increased electrical conductivity around the tip also contributes by increasing the "current-delivering size" of the tip: the so-called "virtual electrode effect." METHODS AND RESULTS: In vitro strips of left ventricular porcine myocardium and in vivo canine left ventricles were ablated. In vitro closed loop tip and showerhead irrigated tip catheters were compared. In vitro and in vivo showerhead tip catheters irrigated with solutions having different ionic content were compared. We found no difference in lesion size for closed loop and showerhead-type catheters (998 +/- 345 vs. 811 +/- 313 mm(3) during power-controlled ablation and 227 +/- 76 vs 318 +/- 127 mm(3) during temperature-controlled ablation). For irrigation with liquids having increasing ionic strength we found a decrease in lesion volume in vitro (361 +/- 249 vs. 812 +/- 229 mm(3) (P < 0.001) for power-controlled and 156 +/- 78 vs. 318 +/- 127 mm(3) (P < 0.05) for temperature-controlled ablation and nonsignificant differences in vivo. CONCLUSIONS: The mechanism for enlarging lesion size during radiofrequency irrigated-tip ablation is that higher power levels can be used. There is no virtual electrode effect caused by the highly conductive surroundings of the tip during irrigation. In vitro this effect is shown to be opposite: it decreases lesion size.

Animals↗

[Treatment with implantable defibrillator].

About 20 years ago the first patient received an implantable cardioverter defibrillator (ICD), and since then the number of implants have increased dramatically. The ICD can terminate ventricular fibrillation and ventricular tachycardia. Studies of secondary prophylaxis show that ICD treatment can improve the prognosis of patients who have survived cardiac arrest. Prophylactic ICD treatment in patients who have not had cardiac arrest is only recommended for selected groups. Patients with poor left ventricular function seem to benefit the most and ongoing trials should elucidate the possible benefit from prophylactic ICD treatment in heart failure patients. The purpose of this article is to describe the development in ICD treatment and give a survey of the present indications for ICD treatment.

Defibrillators, Implantable↗

Can lesion size during radiofrequency ablation be predicted by the temperature rise to a low power test pulse in vitro?

During radiofrequency ablation sufficient power must be delivered to achieve a proper lesion, while tissue temperatures are kept below 100 degrees C. Tissue temperature and hence lesion size are determined by electrode to tissue contact and convective cooling, which vary with any obtained electrode position in the beating heart. A tool for evaluation of the combined effect of these parameters prior to ablation to predict the resulting lesion size for any actually obtained electrode position would be valuable. A low power pulse prior to ablation will cause a small increase in tip temperature, which will reflect tissue contact and convective cooling of the tip for that particular electrode position and may thereby predict lesion dimensions after subsequent ablation at that site. Ablation was performed in vitro on strips of left ventricular porcine myocardium during different levels of convective cooling, variable contact pressure, and two electrode orientations in temperature-controlled and power-controlled modes. A 4-mm tip catheter was used. Prior to ablation a 30-second, 0.6-W test pulse was delivered and the increase in tip temperature (DeltaT) registered. The study found that DeltaT and lesion size were mainly affected by the external cooling of the electrode tip and less by the electrode to tissue contact. Increased cooling caused a lower DeltaT (P < 0.001), and the effect on lesion dimensions depended on the ablation mode. For temperature-controlled ablation a larger lesion due to increased power output was obtained (P < 0.0001) for increased cooling, whereas for power-controlled ablation a smaller lesion was obtained for increased cooling (P < 0.05). DeltaT can predict lesion size, but the interpretation of DeltaT depends on the ablation mode. For temperature-controlled ablation a high DeltaT indicates a small lesion and for power-controlled ablation a high DeltaT indicates a large lesion.

Analysis of Variance↗