Young Keun On

The effects of atorvastatin on the occurrence of postoperative atrial fibrillation after off-pump coronary artery bypass grafting surgery.

BACKGROUND Atrial fibrillation (AF) after coronary artery bypass graft (CABG) surgery is still the most common arrhythmic complication. This study evaluated whether pretreatment with atorvastatin protects against AF after off-pump CABG. METHODS One hundred twenty-four patients without a history of AF or previous statin use, who were scheduled to undergo elective off-pump CABG, were enrolled. Patients were randomized to control group (n = 62) or to atorvastatin group (n = 62) who were administered atorvastatin 20 mg/d for 3 days before the surgery. Primary outcome was the incidence of postoperative AF. Secondary outcomes were major adverse cardiac and cerebrovascular events, persistent AF at 1 month, and identification of the markers to predict inhospital postoperative AF. RESULTS The incidence of AF was significantly lower in the atorvastatin group than in the control group (13% vs 27%, P = .04). The incidence of major adverse cardiac and cerebrovascular events and persistent AF at 1 month was similar in comparisons between the groups. Postoperative peak N-terminal pro-brain natriuretic peptide levels were significantly higher in the patients with AF (P = .03). Multivariate analysis identified pretreatment with atorvastatin as an independent factor associated with a significant reduction in postoperative AF (odds ratio 0.34, P = .04). Higher postoperative peak N-terminus pro-B-type natriuretic peptide levels were associated with the development of postoperative AF (odds ratio 1.02 per 100 pg/mL, P = .03). CONCLUSIONS Pretreatment with atorvastatin significantly reduced the occurrence of postoperative AF after off-pump CABG.

Relation of Fragmented QRS Complex to Right Ventricular Fibrosis Detected by Late Gadolinium Enhancement Cardiac Magnetic Resonance in Adults With Repaired Tetralogy of Fallot

Fragmented QRS (fQRS) on 12-lead electrocardiography reflects conduction delay caused by myocardial fibrosis and dysfunction. Ventricular fibrosis detected by late gadolinium enhancement (LGE) cardiac magnetic resonance (CMR) is reportedly correlated with worse clinical outcomes in adults with repaired tetralogy of Fallot (TOF). The aim of this study was to assess whether the presence of fQRS is associated with right ventricular (RV) fibrosis or dysfunction in this patient group. In 37 consecutive patients (median age 30 years, median age at repair 6.6 years), the number of leads showing fQRS, defined as the presence of >2 notches on the R/S wave in ≥2 contiguous leads, was counted. RV systolic function, dilatation, and LGE score were measured using LGE CMR. Ventricular LGE was observed mainly at the previous surgical sites: the RV outflow tract (33 of 37), ventricular septal defect patch region (15 of 37), and RV anterior wall (11 of 37). Fragmented QRS was found mostly in the right and mid precordial leads. The fQRS group (n = 20) demonstrated higher RV LGE scores (p <0.001) and lower RV ejection fractions (p = 0.02) and a trend toward larger RV end-diastolic and end-systolic volumes (p = 0.12 and p = 0.06, respectively) compared to the non-fQRS group (n = 17). The number of electrocardiographic leads showing fQRS was positively correlated with RV LGE score (r = 0.75, p <0.001). The presence of fQRS remained independently associated with the presence of supramedian RV LGE score, even after adjusting for relevant parameters. In conclusion, fQRS was closely associated with more extensive RV fibrosis and dysfunction in adults with repaired tetralogy of Fallot.

A novel disease gene for Brugada syndrome: sarcolemmal membrane-associated protein gene mutations impair intracellular trafficking of hNav1.5.

Background— Mutations in genes including SCN5A encoding the &agr;-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum. Methods and Results— We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP. Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current. Conclusions— The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel.Background— Mutations in genes including SCN5A encoding the α-subunit of the cardiac sodium channel (hNav1.5) cause Brugada syndrome via altered function of cardiac ion channels, but more than two-thirds of Brugada syndrome remains pathogenetically elusive. T-tubules and sarcoplasmic reticulum are essential in excitation of cardiomyocytes, and sarcolemmal membrane-associated protein (SLMAP) is a protein of unknown function localizing at T-tubules and sarcoplasmic reticulum. Methods and Results— We analyzed 190 unrelated Brugada syndrome patients for mutations in SLMAP . Two missense mutations, Val269Ile and Glu710Ala, were found in heterozygous state in 2 patients but were not found in healthy individuals. Membrane surface expression of hNav1.5 in the transfected cells was affected by the mutations, and silencing of mutant SLMAP by small interfering RNA rescued the surface expression of hNav1.5. Whole-cell patch-clamp recordings of hNav1.5-expressing cells transfected with mutant SLMAP confirmed the reduced hNav1.5 current. Conclusions— The mutations in SLMAP may cause Brugada syndrome via modulating the intracellular trafficking of hNav1.5 channel.

Is Home Orthostatic Self-Training Effective in Preventing Neurally Mediated Syncope?

Background: Repeated orthostatic stress may prove to be of benefit in the regulation of neurally mediated syncope. But the role of home orthostatic self‐training is not established to prevent symptoms in patients with neurally mediated syncope. We performed a prospective and randomized study to evaluate the effectiveness of repeated home orthostatic self‐training in preventing tilt‐induced neurally mediated syncope.

Plasma transforming growth factor β1 as a biochemical marker to predict the persistence of atrial fibrillation after the surgical maze procedure

OBJECTIVES The Cox maze procedure was developed as a surgical treatment for atrial fibrillation. However, atrial fibrillation recurs in some patients, and atrial remodeling in the form of fibrosis can lead to perpetuation of atrial fibrillation. To identify the predictor of the persistence of atrial fibrillation after the maze procedure using cryoablation, we evaluated the preoperative plasma transforming growth factor beta1. We also examined the correlations between plasma transforming growth factor beta1 levels and the degree of atrial fibrosis. METHODS Preoperative plasma transforming growth factor beta1 levels were measured in 86 consecutive patients (age, 54 +/- 12 years) who underwent both the open heart operation for valvular heart disease and the surgical maze procedure with cryoablation for persistent atrial fibrillation. We measured the degree of fibrosis from the tissue of the left atrium. RESULTS At 1 years follow-up, 10 of 86 patients had persistent atrial fibrillation. Patients with persistent atrial fibrillation had higher preoperative plasma transforming growth factor beta1 levels than the patients with sinus rhythm (0.44 +/- 0.29 vs 0.32 +/- 0.15 ng/mL, P = .03). Patients with persistent atrial fibrillation had higher mRNA expressions of collagen III and lower mRNA expressions of atrial natriuretic peptide than those with sinus rhythm, and the plasma transforming growth factor beta1 levels correlated with the degree of fibrosis in the left atrium (r = 0.497, P = .022). Multiple logistic regression analysis revealed that plasma transforming growth factor beta1 levels were independently associated with the postoperative persistence of atrial fibrillation at 1 years follow-up. CONCLUSIONS Preoperative plasma transforming growth factor beta1 levels could be used to predict the persistence of atrial fibrillation at 1 years follow-up after the surgical maze procedure by using cryoablation. Preoperative plasma transforming growth factor beta1 levels were correlated with the degree of fibrosis in the left atria of patients with mitral valvular heart disease.

The Korean Heart Rhythm Society's 2014 Statement on Antithrombotic Therapy for Patients with Nonvalvular Atrial Fibrillation: Korean Heart Rhythm Society

In patients with nonvalvular atrial fibrillation (AF), the risk of stroke varies considerably according to individual clinical status. The CHA2DS2-VASc score is better than the CHADS2 score for identifying truly lower risk patients with AF. With the advent of novel oral anticoagulants (NOACs), the strategy for antithrombotic therapy has undergone significant changes due to its superior efficacy, safety and convenience compared with warfarin. Furthermore, new aspects of antithrombotic therapy and risk assessment of stroke have been revealed: the efficacy of stroke prevention with aspirin is weak, while the risk of major bleeding is not significantly different from that of oral anticoagulant (OAC) therapy, especially in the elderly. Reflecting these pivotal aspects, previous guidelines have been updated in recent years by overseas societies and associations. The Korean Heart Rhythm Society has summarized the new evidence and updated recommendations for stroke prevention of patients with nonvalvular AF. First of all, antithrombotic therapy must be considered carefully and incorporate the clinical characteristics and circumstances of each individual patient, especially with regards to balancing the benefits of stroke prevention with the risk of bleeding, recommending the CHA2DS2-VASc score rather than the CHADS2 score for assessing the risk of stroke, and employing the HAS-BLED score to validate bleeding risk. In patients with truly low risk (lone AF, CHA2DS2-VASc score of 0), no antithrombotic therapy is recommended, whereas OAC therapy, including warfarin (international normalized ratio 2-3) or NOACs, is recommended for patients with a CHA2DS2-VASc score ≥2 unless contraindicated. In patients with a CHA2DS2-VASc score of 1, OAC therapy should be preferentially considered, but depending on bleeding risk or patient preferences, antiplatelet therapy or no therapy could be permitted.

Fragmented QRS complex in adult patients with Ebstein anomaly and its association with arrhythmic risk and the severity of the anomaly.

Background—Fragmented QRS complex (fQRS) on 12-lead ECG, a marker of myocardial scar, is a predictor of arrhythmic events in patients with ischemic and nonischemic cardiomyopathy. We investigated whether the presence of fQRS is associated with the severity of the anomaly and with increased arrhythmic events in adult patients with Ebstein anomaly (EA). Methods and Results—In 51 consecutive adult patients with EA (median age, 37 years; 18 males), the severity index of EA calculated from echocardiographic data and clinical arrhythmic events were analyzed. The extent of fQRS in each patient was measured by counting the number of ECG leads showing fQRS. There were 35 (68.6%) patients with fQRS (fQRS group) and 16 (31.4%) patients without fQRS (non-fQRS group). fQRS was observed more frequently in the inferior (n=26) and precordial (n=25) leads versus the lateral leads (n=5). The patients in the fQRS group had a worse functional class, greater cardiothoracic ratios, more severe tricuspid regurgitation, larger atrialized right ventricular areas, higher EA severity scores, and more frequent arrhythmic events compared with those in the non-fQRS group. The atrialized right ventricular area showed a positive correlation with the fQRS extent (r=0.51; P<0.001). In multivariable Cox regression models, the presence of fQRS was independently associated with arrhythmic events (P=0.036). Conclusions—Fragmented QRS on 12-lead ECG was associated with larger atrialized right ventricular area and an increased risk of arrhythmic events in adult patients with EA.

The Incidence and Predictors of Postoperative Atrial Fibrillation After Noncardiothoracic Surgery

Background and Objectives The incidence of postoperative atrial fibrillation after noncardiothoracic surgery is known to be very rare; there have been few prior studies on this topic. We evaluated the incidence, predictors, and prognosis of atrial fibrillation after noncardiothoracic surgery. Subjects and Methods Patients who underwent noncardiothoracic surgery at our medical center under general anesthesia were enrolled. We reviewed medical records retrospectively and evaluated whether the atrial fibrillation developed postoperatively or was pre-existing. Patients who had a previous history of atrial fibrillation or atrial fibrillation on the pre-operative electrocardiogram were excluded. Results Between January 2005 and December 2006, 7,756 patients (mean age: 69 years, male: 46%) underwent noncardiothoracic surgery in Samsung Medical Center and 30 patients (0.39%) were diagnosed with newly-developed atrial fibrillation. Patients who developed atrial fibrillation were significantly older and had significantly lower body mass indexes. Newly-developed atrial fibrillation was detected in 0.53% of the male patients and 0.26% of the female patients. The incidence of postoperative atrial fibrillation after an emergency operation was more frequent than that of elective operations (p<0.001). According to the multivariate analysis, age and emergency operations were independent predictors for new onset atrial fibrillation after noncardiothoracic surgery. Postoperative atrial fibrillation developed after a median of 2 days after the noncardiothoracic surgery and was associated with a longer hospitalization and increased in-hospital mortality. Four (13.3%) patients died and the causes of death were non-cardiovascular events such as pneumonia or hemorrhage. Conclusion Postoperative atrial fibrillation after noncardiothoracic surgery is a rare complication and is associated with older age and emergency operations. Patients who develop atrial fibrillation have longer hospitalizations and higher in-hospital mortality rates.

Antithrombotic treatment for stroke prevention in atrial fibrillation: The Asian agenda

Atrial fibrillation (AF) is the most common heart arrhythmia. Untreated AF incurs a considerable burden of stroke and associated healthcare costs. Asians have AF risk factors similar to Caucasians and a similarly increased risk of AF-related stroke; however, with a vast and rapidly ageing population, Asia bears a disproportionately large disease burden. Urgent action is warranted to avert this potential health crisis. Antithrombotic therapy with oral anticoagulants is the most effective means of preventing stroke in AF and is a particular priority in Asia given the increasing disease burden. However, AF in Asia remains undertreated. Conventional oral anticoagulation with warfarin is problematic in Asia due to suboptimal control and a propensity among Asians to warfarin-induced intracranial haemorrhage. Partly due to concerns about intracranial haemorrhage, there are considerable gaps between AF treatment guidelines and clinical practice in Asia, in particular overuse of antiplatelet agents and underuse of anticoagulants. Compared with warfarin, new direct thrombin inhibitors and Factor Xa inhibitors are non-inferior in preventing stroke and significantly reduce the risk of life-threatening bleeding, particularly intracranial bleeding. These agents may therefore provide an appropriate alternative to warfarin in Asian patients. There is considerable scope to improve stroke prevention in AF in Asia. Key priorities include: early detection of AF and identification of asymptomatic patients; assessment of stroke and bleeding risk for all AF patients; evidence-based pharmacotherapy with direct-acting oral anticoagulant agents or vitamin K antagonists for AF patients at risk of stroke; controlling hypertension; and awareness-raising, education and outreach among both physicians and patients.

A KCNQ1 mutation causes age-dependant bradycardia and persistent atrial fibrillation

Atrial fibrillation (AF) is the most common arrhythmia. Gain-of-function mutations in KCNQ1, the pore-forming α-subunit of the slow delayed rectifier K current (IKs) channel, have been associated with AF. The purpose of this study was functional assessment of a mutation in KCNQ1 identified in a family with persistent AF and sinus bradycardia. We investigated whether this KCNQ1 missense mutation could form the genetic basis for AF and bradycardia simultaneously in this family. Sanger sequencing in a family with hereditary persistent AF identified a novel KCNQ1 variant (V241F) in a highly conserved region of S4 domain. The proband and her son developed bradycardia and persistent AF in an age-dependent fashion. The other son was a mutation carrier but he showed sinus bradycardia and not AF. Whole-cell patch clamp electrophysiology showed that V241F mutation in KCNQ1 shifted the activation curve to the left and dramatically slowed deactivation, leading to a constitutively open-like phenotype. Computer modeling showed that V241F would slow pacemaker activity. Also, simulations of atrial excitation predicted that V241F results in extreme shortening of action potential duration, possibly resulting in AF. Our study indicates that V241F might cause sinus bradycardia by increasing IKs. Additionally, V241F likely shortens atrial refractoriness to promote a substrate for reentry. KCNQ1 mutations have previously been described in AF, yet this is the first time a mutation in KCNQ1 is associated with age-dependent bradycardia and persistent AF. This finding further supports the hypothesis that sinus node dysfunction contributes to the development of AF.