Stereotactic cardiac radiation for ablation (radioablation) of life-threatening ventricular arrhythmia was recently introduced into clinical practice.A 76-year-old male patient with apical hypertrophic cardiomyopathy at burnout stage, who received defibrillator implantation for the secondary prevention of sudden arrhythmic death, was admitted for repeated defibrillator therapy.Radiofrequency catheter ablation was unsuccessful due to the induction of ventricular fibrillation (VF) and hemodynamically unstable sustained monomorphic ventricular tachycardia (VT).However, intracardiac activation mapping for the induced VT revealed the earliest ventricular activation at the apical aneurysm.Radioablation was performed to control VT and VF storm refractory to antiarrhythmic drug therapy.A total of 24 Gray was radiated, divided into three fractions around the apical aneurysm.The onset of electrical modulation was instantaneous and the antiarrhythmic effect was maintained for at least 6 months without significant radiation toxicities.This case suggests that radioablation may be considered as a rescue therapy for VT and VF storm refractory to other treatment modalities.
Heart rate (HR) control is a mainstay of atrial fibrillation (AF) management. Guidelines recommend first-line β-blockers for HR control in paroxysmal, persistent, or permanent AF.1January C.T. Wann S. Alpert J.S. et al.2014 AHA/ACC/HRS guideline for the management of patients with atrial fibrillation: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the Heart Rhythm Society.J Am Coll Cardiol. 2014; 64: e1-e76Crossref PubMed Scopus (3017) Google Scholar Carvedilol, a non-selective β-blocker, has a documented HR-lowering effect; in a dose-escalation study of Japanese patients with chronic AF (AF Carvedilol study), each dose of carvedilol (5, 10 or 20 mg, once daily) significantly reduced HR from baseline (HR ≥80 bpm) during 6 weeks of treatment.2Inoue H. Atarashi H. Okumura K. et al.Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.J Cardiol. 2017; 69: 293-301Abstract Full Text Full Text PDF PubMed Google Scholar Although off-label carvedilol indications include AF,3Singh S. Carvedilol. 2022; Accessed February 23, 2024. https://www.statpearls.com/ArticleLibrary/viewarticle/102Google Scholar there are currently no phase 3 clinical trial data to support carvedilol use for HR control in patients with AF. We report results from a phase 3, multicenter, randomized, double-blind, placebo-controlled trial of patients with persistent or permanent AF treated with once-daily carvedilol (Dilatrend® SR Capsule, Chong Kun Dang Pharmaceutical, Seoul, Republic of Korea) 8, 16 or 32 mg for 6 weeks (NCT03950843). Eligible patients who received carvedilol during the 6-week treatment period entered a 4-week open-label extension. Overall, 154 subjects were enrolled (safety analysis set [SAS]). Subjects in the full analysis set received carvedilol (n = 93) or placebo (n = 42): mean (SD) age 66.4 (9.6) years, mostly male (72.6%), with a mean (SD) resting HR of 98.3 (14.7) bpm, and CHA2DS2-VASc score of 2.43 (1.64), and the majority (80.7%) had a modified European Heart Rhythm Association (EHRA) score of 2a. Most subjects had persistent AF (77.0%) and the mean (SD) AF duration was 60.7 (73.8) months. There were no significant between group differences in baseline characteristics. Change in 24-hour mean HR from baseline to week 6 (primary endpoint) was reduced significantly by carvedilol vs. placebo (P < 0.0001; Figure 1A); changes were maintained in the 4-week extension period. Post-hoc subgroup analysis showed that changes in 24-hour mean HR from baseline to week 6 with carvedilol were dose-dependent: respective mean (SD) changes for carvedilol 8 mg (n = 14), 16 mg (n = 26), and 32 mg (n = 53) were −5.07 (5.97), −9.69 (6.34), and −7.58 (8.00) (P = 0.0072, P < 0.0001, and P < 0.0001, respectively). More subjects achieved HR <80 bpm at week 6 (secondary endpoint) in carvedilol vs. placebo groups (30.1% vs. 14.3%; P = 0.0499), with a risk difference of 15.82 (95% confidence interval: 1.72–29.93). Carvedilol was associated with significant improvement in modified EHRA scores from baseline to week 6 (P < 0.0001; secondary endpoint). Mean hourly HR at baseline was similar between the two groups (Figure 1B, upper panel) but, at week 6, carvedilol produced significant changes from baseline in mean HR at each hourly time point. In contrast, no significant changes from baseline in hourly mean HR were found in the placebo group. At week 6, modest but significant decreases in mean hourly HR were generally observed with carvedilol compared to placebo during the daytime, but there were fewer significant between-group differences at nighttime (exploratory endpoints; Figure 1B, lower panel). In the SAS, 60 treatment-emergent adverse events (TEAEs) were reported in 43 subjects (27.9%) during the 6-week trial: 43 AEs in 31 subjects (29.8%) in the carvedilol group, and 17 in 12 subjects (24.0%) in the placebo group. Most TEAEs were mild (41 cases) or moderate (18 cases) in severity. The most common TEAEs were dizziness in 9 subjects (5.8%) and dyspnea in 7 subjects (4.6%). This is the first pivotal phase 3 clinical trial to show the efficacy of once-daily carvedilol for HR control in patients with AF. Compared with placebo, carvedilol significantly decreased 24-hour mean HR from baseline to week 6 and this effect was maintained during the 4-week extension period. Changes were dose-dependent with higher carvedilol doses (16 and 32 mg) effecting larger changes than the 8 mg dose. Similar results were reported in the AF Carvedilol Japanese trial of patients with persistent or permanent AF, which demonstrated that once-daily carvedilol significantly reduced HR from baseline during 6 weeks of treatment.2Inoue H. Atarashi H. Okumura K. et al.Heart rate control by carvedilol in Japanese patients with chronic atrial fibrillation: The AF Carvedilol study.J Cardiol. 2017; 69: 293-301Abstract Full Text Full Text PDF PubMed Google Scholar In conclusion, carvedilol for 6 weeks was effective in reducing HR in patients with AF and maintained efficacy during the extension period. Carvedilol was well tolerated and the safety profile was consistent with previous reports.
East Asians treated with potent P2Y12 inhibitors (prasugrel or ticagrelor) generally experience more intense platelet inhibitory responses resulting in an increased risk of major bleeding. Whether a half-dose de-escalation strategy improves the net clinical benefit in Korean patients with acute coronary syndrome (ACS) remains uncertain. A total of 120 patients were pragmatically randomized to either prasugrel (
A 51-year-old male patient was referred for a sudden out-of-hospital cardiac arrest. Upon arrival, he was conscious and had no chest pain complaints. There was no abnormality in initial electrocardiographic and echocardiographic examinations. However, episodes of recurrent ventricular fibrillation (VF) were documented on rhythm monitoring. Each VF episode was triggered by an isolated monomorphic ventricular premature complex (VPC). Suspecting idiopathic VF, emergency radiofrequency catheter ablation was planned for the VPCs. However, when coronary angiography was performed to exclude silent ischemia, the results showed a total occlusion of the right coronary artery posterolateral branch, which is thought to supply the left ventricular inferior and septal wall. After successful reperfusion, VF episodes and the triggering VPCs disappeared. We are documenting this case to emphasize the potential for silent myocardial infarction to cause out-of-hospital sudden cardiac arrest even in a patient without any symptom or sign of acute coronary syndrome. Key Words: myocardial infarction; out-of-hospital cardiac arrest; ventricular fibrillation; ventricular premature complexes.
Background: High sodium and low potassium consumption are related to hypertension and cardiovascular disease. We aimed to determine the relationship between the frequency of salt addition and potassium consumption with the risk of new-onset atrial fibrillation (AF). Methods: Our study used the UK Biobank cohort, which included over 500,000 individuals enrolled from the United Kingdom between 2006 and 2010. This study involved 416,868 participants who filled out the dietary recall regarding the frequency of salt addition. Results: During follow-up, 19,164 (4.6%) developed AF. The incidence of new-onset AF was increased based on the frequency of salt addition (never/rarely 3.83; always 4.72 per 1000 person-years). Compared with the group that never/rarely added salt, those adding salt always were at significantly higher risk of incident AF after adjusting for multiple variables (hazard ratio (HR) 1.15; 95% confidence interval (CI) 1.06–1.24), and additional adjustment of dietary and total energy consumption (HR 1.37; 95% CI 1.08–1.73). In the subgroup analysis, the risk of AF incident according to the frequency of salt addition significantly increased in low urine potassium levels compared to high (p for interaction = 0.046). In the subgroup analysis for AF patients, higher salt addition frequency was related to increased all-cause mortality. Conclusions: Our study demonstrated that adding salt to foods more frequently increases the risk of incident AF, even after adjusting for dietary and total energy consumption. In the high urine potassium group, the impact of high sodium consumption on incident AF was attenuated.
The diagnosis of myocardial infarction (MI) needs to be swift and accurate, but definitively diagnosing it based on the first test encountered in clinical practice, the electrocardiogram (ECG), is not an easy task. The purpose of the study is to develop a deep learning (DL) algorithm using multitask learning method to differentiate patients experiencing MI from those without coronary artery disease using image-based ECG data.
The activation of innate immunity requires the amplification of signals induced by pattern-recognition receptors for bacterial products. We have investigated the role of the newly described cytokine IL-32 in the amplification of cytokine production induced by the two most clinically relevant families of microbial receptors, the cell-surface Toll-like receptors (TLRs) and the intracellular nuclear oligomerization domain (NOD) receptor family. IL-32 synergized with the NOD1- and NOD2-specific muropeptides of peptidoglycans for the release of IL-1β and IL-6 (a 3- to 10-fold increase). In contrast, IL-32 did not influence the cytokine production induced via TLRs. The synergistic effect of IL-32 and synthetic muramyl dipeptide (MDP) on cytokine production was absent in the cells of patients with Crohn's disease bearing the NOD2 frameshift mutation 3020insC, demonstrating that the IL-32/MDP synergism depends on NOD2. This in vitro synergism between IL-32 and NOD2 ligands was consistent with a marked constitutive expression of IL-32 in human colon epithelial tissue. In addition, the potentiating effect of IL-32 on the cytokine production induced by the synthetic muropeptide FK-156 was absent in NOD1-deficient macrophages, supporting the interaction between IL-32 and NOD1 pathways. When specific caspase inhibitors were used, the synergism between IL-32 and MDP/NOD2 depended on the activation of caspase 1. Only additive effects of IL-32 and muropeptides were observed for TNF-α production. The modulation of intracellular NOD2 pathways by IL-32, but not cell-surface TLRs, and the marked expression of IL-32 in colon mucosa suggest a role of IL-32 in the pathogenesis of Crohn's disease.
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