The utility of zebrafish cardiac arrhythmia model to predict the pathogenicity of KCNQ1 variants.

Genetic testing for inherited arrhythmias and discriminating pathogenic or benign variants from variants of unknown significance (VUS) is essential for gene-based medicine. KCNQ1 is a causative gene of type 1 long QT syndrome (LQTS), and approximately 30% of the variants found in type 1 LQTS are classified as VUS. We studied the role of zebrafish cardiac arrhythmia model in determining the clinical significance of KCNQ1 variants. We generated homozygous kcnq1 deletion zebrafish (kcnq1del/del) using the CRISPR/Cas9 and expressed human Kv7.1/MinK channels in kcnq1del/del embryos. We dissected the hearts from the thorax at 48 h post-fertilization and measured the transmembrane potential of the ventricle in the zebrafish heart. Action potential duration was calculated as the time interval between peak maximum upstroke velocity and 90% repolarization (APD90). The APD90 of kcnq1del/del embryos was 280 ± 47 ms, which was significantly shortened by injecting KCNQ1 wild-type (WT) cRNA and KCNE1 cRNA (168 ± 26 ms, P < 0.01 vs. kcnq1del/del). A study of two pathogenic variants (S277L and T587M) and one VUS (R451Q) associated with clinically definite LQTS showed that the APD90 of kcnq1del/del embryos with these mutant Kv7.1/MinK channels was significantly longer than that of Kv7.1 WT/MinK channels. Given the functional results of the zebrafish model, R451Q could be reevaluated physiologically from VUS to likely pathogenic. In conclusion, functional analysis using in vivo zebrafish cardiac arrhythmia model can be useful for determining the pathogenicity of loss-of-function variants in patients with LQTS.

Characterization of baseline clinical factors associated with incident worsening kidney function in patients with non-valvular atrial fibrillation: the Hokuriku-Plus AF Registry.

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0 years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15 mL/min/1.73 m2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0 years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75 years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75 years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible.

A case of torsades de pointes due to takotsubo cardiomyopathy after common atrial flutter ablation.

Takotsubo cardiomyopathy (TCM) is a transient acute cardiac disorder often associated with QT prolongation, but this rarely leads to torsades de pointes (TdP). Additionally, it is a rare complication of catheter ablation. Here we report a case of TCM that developed after catheter ablation for common atrial flutter, which led to TdP. The patient was an 85-year-old male who had persistent supraventricular tachycardia, which was considered atrial flutter. The patient was hospitalized for congestive heart failure. Although the response to diuretic administration was unfavorable, heart failure improved with the combined use of rate control by landiolol. Catheter ablation was performed because of the possibility of tachycardia-induced cardiomyopathy. Tachycardia disappeared following ablation to the cavotricuspid isthmus, but the patient complained of severe pain during the ablation. Approximately 2 h after the treatment, the patient's heart failure re-exacerbated. The next day, electrocardiogram confirmed a marked QT prolongation, and TdP occurred. Although the phenomenon we experienced is rarely reported, it should be considered a complication following catheter ablation. Adequate analgesia, care for anxiety about treatment, and evaluation of cardiac condition after treatment are considered important. .

Coronary intervention for severe stenosis in the ostial right coronary artery with cardiac angiosarcoma: a case report.

BACKGROUND: Although rare, angiosarcoma is the most common type of cardiac primary malignancy. This disease can cause life-threatening complications and the prognosis remains poor. There is no standard approach to care, and clinical judgement is exercised on a case-by-case basis. Tumour progression causes serious complications, such as heart failure and vascular disruption. CASE SUMMARY: A 64-year-old Japanese woman presenting with a right atrial tumour was referred to our department. Tumour biopsy revealed that the patient suffered from angiosarcoma. We performed a lumpectomy to excise the tumour, but due to tissue adhesions in and around the right atrium, the malignancy could not be completely removed. After 3 years of chemotherapy, the patient was admitted to our hospital with increased chest pain. Emergency coronary angiogram revealed severe stenosis of the ostial right coronary artery. Intravascular ultrasound (IVUS) and computed tomography suggested coronary compression due to cardiac angiosarcoma. In this study, we report a unique case of advanced cardiac angiosarcoma, presenting as unstable angina, which was successfully treated with percutaneous coronary intervention using stent implantation. DISCUSSION: Due to the rarity of cardiac primary angiosarcoma, many symptoms are misdiagnosed until mechanical complications arise, such as coronary compression. The clinical course and various imaging modalities are useful for differentiating angiosarcomas from coronary stenosis.

Impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after catheter ablation of atrial fibrillation: insights from AF frontier ablation registry.

The impact of catheter ablation for atrial fibrillation (AF) on cardiovascular events and mortality is controversial. We investigated the impact of sinus rhythm maintenance on major adverse cardiac and cerebrovascular events after AF ablation from a Japanese multicenter cohort of AF ablation. We investigated 3326 consecutive patients (25.8% female, mean age 63.3 ± 10.3 years) who underwent catheter ablation for AF from the atrial fibrillation registry to follow the long-term outcomes and use of anti coagulants after ablation (AF frontier ablation registry). The primary endpoint was a composite of stroke, transient ischemic attack, cardiovascular events, and all-cause death. During a mean follow-up of 24.0 months, 2339 (70.3%) patients were free from AF after catheter ablation, and the primary composite endpoint occurred in 144 (4.3%) patients. The AF nonrecurrence group had a significantly lower incidence of the primary endpoint (1.8 per 100 person-years) compared with the AF recurrence group (3.0 per 100 person-years, p = 0.003). The multivariate analysis revealed that freedom from AF (hazard ratio 0.61, 95% confidence interval 0.44-0.86, p = 0.005) was independently associated with the incidence of the composite event. In the multicenter cohort of AF ablation, sinus rhythm maintenance after catheter ablation was independently associated with lower rates of major adverse cardiac and cerebrovascular events.

Effect on Plasma Protein S Activity in Patients Receiving the Factor Xa Inhibitors.

AIMS: Measurement of protein S (PS) activity in patients taking direct oral anticoagulants (DOACs) using reagents based on a clotting assay results in falsely high PS activity, thus masking inherited PS deficiency, which is most frequently seen in the Japanese population. In this study, we investigated the effect of factor Xa (FXa) inhibitors on PS activity using the reagent on the basis of the chromogenic assay, which was recently developed in Japan. METHODS: The study enrolled 152 patients (82 males and 70 females; the average age: 68.5±14.0 years) receiving three FXa inhibitors (rivaroxaban, edoxaban, and apixaban). PS activity was measured using the reagents on the basis of the clotting and chromogenic assays. RESULTS: PS activity measured by the clotting assay reagents exhibited falsely high values depending on the plasma concentrations of FXa inhibitors in patients taking either rivaroxaban or edoxaban. However, none of the three FXa inhibitors affected PS activity when measured using the chromogenic assay. CONCLUSION: In patients taking rivaroxaban or edoxaban, inherited PS deficiency is likely missed because the levels of PS activity measured using the reagents based on the clotting assay are falsely high. However, we report that three FXa inhibitors do not affect PS activity measured by the chromogenic assay. When measuring the levels of PS activity in patients undergoing DOACs, the principles of each reagent should be understood. Furthermore, plasma samples must be collected at the time when plasma concentrations of DOACs are lowest or the DOAC-Stop reagent should be used.

Transient swallowing-induced atrial tachycardia in a patient with genotyped hypertrophic cardiomyopathy.

Most cases of swallowing-induced atrial tachycardia require radiofrequency catheter ablation for a permanent cure; however, the arrhythmia subsided after temporary prescription of verapamil in a patient with genotyped hypertrophic cardiomyopathy.

A case of pulmonary arterial hypertension with chronic hepatitis that resulted in hepatosplenomegaly after administration of prostaglandin I2.

The prognosis of pulmonary arterial hypertension (PAH) has significantly improved over the past two decades due to advances in medications, including pulmonary vasodilators. However, the side effects of these drugs remain problematic in some patients. A 51-year-old woman with chronic hepatitis C was diagnosed with PAH 7 years before presenting to our hospital. She was unable to continue her treatment with pulmonary vasodilators due to various side effects. She had a World Health Organization functional class of IV and was started on continuous infusion of prostaglandin I2 (PGI2). This therapy improved her symptoms, including dyspnea and fatigue. However, she began to complain of abdominal distension after 4 months of PGI2 therapy. Computed tomography showed significant hepatosplenomegaly. Her abdominal distension improved slightly after decreasing PGI2 treatment, but her dyspnea on exertion was exacerbated. She died 12 years after diagnosis of PAH due to uncontrollable heart failure. Here, we describe a rare case of PAH with hepatosplenomegaly after administration of PGI2. .

Renal iodine123-metaiodobenzylguanidine scintigraphy relates to muscle sympathetic nervous activity in heart failure with reduced ejection fraction.

BACKGROUND: Renal denervation is effective for modulating augmented sympathetic nerve activity (SNA) in heart failure with reduced ejection fraction (HFrEF). We have demonstrated that renal iodine123-metaiodobenzylguanidine (123I-MIBG) scintigraphy is associated with muscle sympathetic nerve activity (MSNA) in patients with hypertension. However, it is unclear whether renal 123I-MIBG scintigraphy is useful for assessment of SNA in HFrEF. METHODS: The study population consisted of 24 HFrEF patients and 11 healthy subjects as controls. Patients with HFrEF underwent 123I-MIBG scintigraphy and hemodynamics using a Swan-Ganz catheter (SGC). HFrEF was defined as echocardiography with left ventricular ejection fraction (LVEF) < 50%. MSNA was measured from the peroneal nerve for direct evaluation of SNA. Renal 123I-MIBG scintigraphy was performed simultaneously with cardiac scintigraphy. The early and delayed kidney-to-mediastinum ratio (K/M), early and delayed heart-to-mediastinum ratio (H/M), and washout rate (WR) were calculated. RESULTS: LVEFs were 35% ± 11% in patients with HFrEF and 63% ± 10% in the controls (p < 0.01). The WR of cardiac 123I-MIBG showed no relation to MSNA, but was related to stroke volume (r = 0.45, p < 0.05). In contrast, the WR of renal 123I-MIBG scintigraphy (average of both sides) showed a strong correlation with MSNA (BI, r = 0.70, p < 0.01; BF, r = 0.66, p < 0.01); however, no significant correlations were detected between renal 123I-MIBG scintigraphy and SGC results. CONCLUSIONS: The WR of renal 123I-MIBG scintigraphy may reflect MSNA. Further studies are needed to clarify the relationship between renal 123I-MIBG imaging and renal SNA.

Takotsubo cardiomyopathy complicated by cardiac tamponade due to non-hemorrhagic pericardial effusion: a case report.

BACKGROUND: Cardiac tamponade is a rare but serious complication of Takotsubo cardiomyopathy (TC). Two cases of cardiac tamponade subsequent to TC have been reported. The pericardial effusion in these cases was hemorrhagic and caused by ventricular rupture. Cardiac tamponade induced by an inflammatory effusion complicated with TC has not been reported. This is the first case report of TC, which developed cardiac tamponade during the recovery phase with a large volume non-hemorrhagic inflammatory effusion. CASE PRESENTATION: We describe a case of an 81-year-old woman admitted to our hospital because of severe chest pain. Her symptoms began soon after her son's hospitalization. We diagnosed her with TC based on results of an electrocardiogram, echocardiogram, and emergent coronary angiography. Her symptoms and left ventricular dysfunction improved gradually. She developed newly confirmed chest pain and dyspnea on day 9 after admission. A large pericardial effusion developed, resulting in cardiac tamponade. Her symptoms and hemodynamic status improved immediately after the pericardiocentesis. The effusion was non-hemorrhagic and exudative. No specific signs of infection, collagen disease, or malignant tumors were observed, except for TC. CONCLUSIONS: We experienced a case of circulatory collapse induced by TC-related inflammatory pericardial effusion at recovery phase. This case emphasizes the importance of careful follow-up even after improved left ventricular dysfunction in a patient with TC.

Impact of functional studies on exome sequence variant interpretation in early-onset cardiac conduction system diseases.

AIMS: The genetic cause of cardiac conduction system disease (CCSD) has not been fully elucidated. Whole-exome sequencing (WES) can detect various genetic variants; however, the identification of pathogenic variants remains a challenge. We aimed to identify pathogenic or likely pathogenic variants in CCSD patients by using WES and 2015 American College of Medical Genetics and Genomics (ACMG) standards and guidelines as well as evaluating the usefulness of functional studies for determining them. METHODS AND RESULTS: We performed WES of 23 probands diagnosed with early-onset (<65 years) CCSD and analysed 117 genes linked to arrhythmogenic diseases or cardiomyopathies. We focused on rare variants (minor allele frequency < 0.1%) that were absent from population databases. Five probands had protein truncating variants in EMD and LMNA which were classified as 'pathogenic' by 2015 ACMG standards and guidelines. To evaluate the functional changes brought about by these variants, we generated a knock-out zebrafish with CRISPR-mediated insertions or deletions of the EMD or LMNA homologs in zebrafish. The mean heart rate and conduction velocities in the CRISPR/Cas9-injected embryos and F2 generation embryos with homozygous deletions were significantly decreased. Twenty-one variants of uncertain significance were identified in 11 probands. Cellular electrophysiological study and in vivo zebrafish cardiac assay showed that two variants in KCNH2 and SCN5A, four variants in SCN10A, and one variant in MYH6 damaged each gene, which resulted in the change of the clinical significance of them from 'Uncertain significance' to 'Likely pathogenic' in six probands. CONCLUSION: Of 23 CCSD probands, we successfully identified pathogenic or likely pathogenic variants in 11 probands (48%). Functional analyses of a cellular electrophysiological study and in vivo zebrafish cardiac assay might be useful for determining the pathogenicity of rare variants in patients with CCSD. SCN10A may be one of the major genes responsible for CCSD.

Optimization of the hot balloon ablation strategy using real-time pulmonary vein potential monitoring.

INTRODUCTION: Optimal radiofrequency-generated thermal energy applications have not been established for hot balloon ablation (HBA) systems. We investigated the feasibility of real-time monitoring of pulmonary vein (PV) potentials and optimal time-to-isolation (TTI)-guided application strategies in HBAs. METHODS AND RESULTS: Real-time monitoring of PV potentials was performed using a four-electrode unidirectional catheter in 34 consecutive patients. Acute isolation was achieved when PV potentials disappeared during HBAs and were undetected by high-resolution mapping. The TTI, the difference between TTI and the time to reach target temperature (TTRT), and ablation time after isolation were examined for 177 applications in 136 PVs. Real-time monitoring of PV activity was obtained in 167 out of 177 applications (94.3%) and acute isolation was achieved in 97 out of 177 (54.8%) applications. TTI-TTRT was significantly shorter, and ablation times after isolation were significantly longer in the acute isolation group than in the other groups. TTI-TTRT <4.5 seconds and TTIs <33.5 seconds predicted acute isolation (sensitivity 74.2%, specificity 88.4%; sensitivity 76.3%, specificity 76.7%, respectively). Ablation time after isolation >148.5 seconds (sensitivity 93.6%, specificity 51.7%) and >120.5 seconds (sensitivity 84.0%, specificity 78.6%) predicted acute isolation in superior PVs and inferior PVs, respectively. CONCLUSIONS: Real-time assessment of PV isolation can be achieved during HBAs with single-shot techniques. (TTI-TTRT)s <4.5 seconds and TTIs <33.5 seconds predicted for acute isolation. Ablation time after isolation >148.5 seconds in superior PVs and >120.5 seconds in inferior PVs were effective application durations.

Quick sepsis-related organ failure assessment score as a possible predictor for in-hospital adverse events in infective endocarditis.

AIM: Infective endocarditis (IE) can be life-threatening because of various associated adverse events. The quick Sepsis-related Organ Failure Assessment (qSOFA) score is a straightforward useful method for predicting in-hospital mortality in patients with suspected infections. However, few data exist regarding the clinical impact of the qSOFA score on predicting adverse events in IE during hospitalization. We studied the usefulness of qSOFA score for predicting in-hospital adverse events in patients with IE. METHODS: We retrospectively analyzed 104 consecutive patients diagnosed with IE on the basis of modified Duke criteria. We defined in-hospital adverse events as occurrence of any of the following events during hospitalization: death, embolism, hemorrhage, or abscess formation. The high qSOFA group was defined as those with a qSOFA score ≥2. We used Cox regression analysis to estimate the hazard ratio for high qSOFA score on in-hospital adverse events adjusted for age, sex, and Staphylococcus aureus infection. RESULTS: We analyzed 83 patients (57 men, mean age 61 ± 18 years) from the total cohort of 104 patients enrolled. Among these, 12 (14.5%) had high qSOFA scores. The high qSOFA group had higher in-hospital mortality compared to the low qSOFA group (50.0% vs. 4.2%, P < 0.01). In the Cox proportional hazards model, high qSOFA was significantly associated with in-hospital adverse events (adjusted hazard ratio, 2.29; confidence interval, 1.02-5.12; P = 0.044). CONCLUSION: These results showed that high qSOFA score was significantly associated with in-hospital adverse events in IE patients, although further prospective study is necessary to confirm our results.

Coronary sinus catheter placement via left cubital vein for phrenic nerve stimulation during pulmonary vein isolation.

Phrenic nerve (PN) stimulation is essential for the elimination of PN palsy during balloon-based pulmonary vein isolation (PVI). Although ultrasound-guided vascular access is safe, insertion of a PN stimulation catheter via central venous access carries a potential risk of the development of mechanical complications. We evaluated the safety of a left cubital vein approach for positioning a 20-electrode atrial cardioversion (BeeAT) catheter in the coronary sinus (CS), and the feasibility of right PN pacing from the superior vena cava (SVC) using proximal electrodes of the BeeAT catheter. In total, 106 consecutive patients who underwent balloon-based PVI with a left cubital vein approach for BeeAT catheter positioning were retrospectively assessed. The left cubital approach was successful in 105 patients (99.1%), and catheter insertion into the CS was possible for 104 patients (99.0%). Among these patients, constant right PN pacing from the SVC was obtained for 89 patients (89/104, 85.6%). In five patients, transient loss of right PN capture occurred during right pulmonary vein ablation. No persistent right PN palsy was observed. Small subcutaneous hemorrhage was observed in eight patients (7.5%). Neuropathy, pseudoaneurysm, arteriovenous fistula, and perforations associated with the left cubital approach were not detected. Body mass index was significantly higher in the right PN pacing failure group than in the right PN pacing success group (26.2 ± 3.2 vs. 23.8 ± 3.8; P = 0.025). CS catheter placement with a left cubital vein approach for right PN stimulation was found to be safe and feasible. Right PN pacing from the SVC using a BeeAT catheter was successfully achieved in the majority of the patients. This approach may prove to be preferable for non-obese patients.

Cost-effectiveness for prevention of thromboembolism by anticoagulants in non-valvular atrial fibrillation: additional analysis from the Hokuriku-Plus AF Registry.

Although benefits of direct oral anticoagulants (DOAC) for treatment of non-valvular atrial fibrillation (AF) were well demonstrated, few data exist regarding cost-effectiveness between DOAC and warfarin uses in real-world clinical practice. Therefore, we estimated total cost of treatment for AF by authorized cardiologists in Japan. We studied consecutive 617 anticoagulated non-valvular AF patients (418 men, mean age 68.8, 54% warfarin) consulted by authorized cardiologists. The mean time in therapeutic range of warfarin was 71.8%. Under these conditions, we calculated the cost of anticoagulants, laboratory examination, and hospitalization due to thromboembolism or bleeding during follow-up for 3.1 years. Thromboembolism occurred in 26 patients (4.2%, 1.3/100 person-year) and hemorrhagic events in 20 patients (3.2%, 1.0/100 person-year). There was no significant difference in the occurrence rate of thromboembolism (log rank P = 0.16) or hemorrhagic events (log rank P = 0.83) between these two groups. Importantly, warfarin group showed lower cost than DOAC group (117,361 ± 743,710 yen/year vs. 310,436 ± 1,075,639 yen/person, P = 0.009) in terms of cost including drug, medical check, and hospitalization. These results demonstrate that the total cost with warfarin can be lower than DOAC in treatment for AF by authorized cardiologists in Japan, although further prospective randomized cost calculation is necessary including post-discharge care fee.

Effect of hypertrophic cardiomyopathy on the prediction of thromboembolism in patients with nonvalvular atrial fibrillation.

BACKGROUND: Anticoagulation is recommended for hypertrophic cardiomyopathy (HCM) with nonvalvular atrial fibrillation (NVAF) according to European and American guidelines. However, it is unclear whether HCM is a risk factor for thromboembolism in NVAF in Japan, and the management for NVAF with HCM is not established. OBJECTIVE: We studied the impact of concomitant HCM on predicting thromboembolism in NVAF. METHODS: We retrospectively studied consecutive 2374 Japanese patients with NVAF (1682 men, 70.9%; mean age 71±10 years). Clinical factors were evaluated using the Cox proportional hazards model. We also investigated whether adding HCM to CHADS2 or CHA2DS2-VASc score improved the prediction of thromboembolism. RESULTS: Thromboembolism was observed in 122 patients (5.1%) during the median follow-up of 2.4 years (interquartile range 2.0-3.2 years). The Cox proportional hazards model showed that HCM was significantly associated with thromboembolism after adjustment for CHADS2 or CHA2DS2-VASc score (hazard ratio 3.41; 95% confidence interval [CI] 1.98-5.73; P<.0001 and hazard ratio 3.38; 95% CI 1.97-5.64; P<.0001, respectively). NVAF with HCM had significantly higher thromboembolism rates, even in those with a CHADS2 or CHA2DS2-VASc score of 1 or 0-1, respectively. Based on the comparison of C-statistics, the addition of HCM to CHADS2 or CHA2DS2-VASc score significantly improved the prediction of thromboembolism (C-statistics 0.75 vs 0.71; P=.003 and C-statistics 0.77 vs 0.71; P=.0001, respectively). CONCLUSION: HCM is an independent risk factor for thromboembolism in patients with NVAF. A markedly high incidence of thromboembolism is observed in NVAF patients with HCM with CHA2DS2-VASc score of both ≥2 and 0-1, and anticoagulation therapy is recommended for them.

Endogenous muscle atrophy F-box is involved in the development of cardiac rupture after myocardial infarction.

Muscle atrophy F-box (MAFbx/atrogin-1), an E3 ubiquitin ligase, is a crucial mediator of skeletal muscle atrophy and cardiac hypertrophy in response to pressure overload and exercise. The role of MAFbx in the regulation of cardiac remodeling after myocardial infarction (MI) remains unclear. Permanent coronary ligation of the left coronary artery was performed on MAFbx knockout (KO) and wild-type (WT) mice and MAFbx expression in the WT mice was shown to be significantly increased in the left ventricles after MI. The mortality rate due to post-MI cardiac rupture was significantly decreased in MAFbx KO mice compared to that in the WT mice. DNA microarray and mRNA expression analyses revealed that the upregulation of genes involved in inflammatory processes and cell motility of leukocytes and neutrophils, including Mmp9, Il1b, Cxcl2, and Nlrp3, was significantly attenuated in MAFbx KO mice 1 day after MI. MAFbx downregulation inhibited nuclear factor-κB (Nfkb) activation after MI. Flow cytometry results demonstrated that the myocardial infiltration of neutrophils was suppressed in MAFbx KO mice 1 day after MI. Nlrp3 and Il1b protein levels were decreased in MAFbx KO mice compared with those in the WT mice. MAFbx downregulation significantly attenuated Tnfa-induced Cxcl2, Il1b, and Nlrp3 expression in cardiomyocytes. We conclude that MAFbx plays an important role in the mediation of excessive inflammation, including neutrophil infiltration, inflammasome formation, and production of proinflammatory cytokines through the activation of Nfkb, promoting cardiac rupture after MI.

Characteristics of synthesized right-sided chest electrocardiograms in patients with acute pulmonary embolism.

BACKGROUND: The significance of right-sided chest lead electrocardiogram (ECG) abnormalities in acute pulmonary embolism (APE) is unclear. This study evaluated the characteristics of such abnormalities in APE patients. METHODS: This retrospective study included consecutive patients who were diagnosed with APE by contrast-enhanced computed tomography or pulmonary artery angiography. A standard 12-lead ECG and a synthesized right-sided chest ECG were obtained from these patients. Waveform differences were noted between the acute and post-treatment phases. RESULTS: In total, 56 APE patients (18 men and 38 women, mean age 66.7±13.3 years) were included. Traditional ECG findings, such as right-axis deviation, the S1Q3T3 pattern, and clockwise rotation, were found in relatively few patients (14.3%, 32.1%, and 21.4%, respectively). In some cases, a negative T wave in standard 12-lead ECGs was observed in leads III, V1, and V2 (46.4%, 60.7%, and 39.9%, respectively). Syn-V3R ECG showed a higher frequency of negative T waves (66.1%) at the onset and significantly (p<0.01) decreased at the follow-up. Multiple logistic regression analyses for differentiating APE revealed that the negative T waves only in lead syn-V3R were significantly related (odds ratio: 6.95, 95% confidence interval: 2.50-19.32, p<0.001). CONCLUSIONS: The presence of a negative T wave in a synthesized right-sided chest ECG, particularly in the V3R lead, is a new and distinctive finding denoting pulmonary embolism. To confirm the utility of this characteristic using synthesized right-sided chest ECGs for the diagnosis of APE, further studies with larger populations will be required.