Genetic Variants Associated With Susceptibility to Atrial Fibrillation in a Japanese Population.

BACKGROUND: Atrial fibrillation (AF) affects millions of individuals worldwide. The genome-wide association studies have identified robust genetic associations with AF. METHODS: We genotyped 5461 participants of Japanese ancestry for 11 AF-related loci and determined the effects of carrying different numbers of risk alleles on disease development and age at disease onset. The weighted genetic risk score (GRS) was calculated, and its ability to predict AF was determined. RESULTS: Six single-nucleotide polymorphisms-rs593479 (1q24 in PRRX1), rs1906617 (4q25 near PITX2), rs11773845 (7q31 in CAV1), rs6584555 (10q25 in NEURL), rs6490029 (12q24 in CUX2), and rs12932445 (16q22 in ZFHX3) (P < 1.9 × 10-5)-were confirmed as being associated with AF. Patients with a high total number of risk alleles (9-12) had a younger median age at onset of AF (58 years; 95% confidence interval [CI], 55-60 years) than those with a low total number (1-4) (63 years; 95% CI, 61-64 years) (P = 0.0015). We observed a 4.38-fold (95% CI, 3.69-5.19) difference in risk of AF between individuals with scores in the top and bottom quartiles of the GRS. Receiver operating characteristic analysis indicated an area under the curve of 0.641 (95% CI, 0.628-0.653; P < 0.0001). CONCLUSIONS: Six loci were validated as associated with AF in a Japanese population. This study suggests that a combination of common genetic markers modestly facilitates discrimination of AF. This is the first report, to our knowledge, to demonstrate that the age of onset of AF is affected by common risk alleles.

Impact of smoking on coronary microcirculatory resistance in patients with coronary artery disease.

The aim of this study was to investigate the relationship between coronary microvascular function and smoking using the 3 parameters fractional flow reserve (FFR), coronary flow reserve (CFR(thermo)), and index of microcirculatory resistance (IMR) in patients with coronary artery disease (CAD). A total of 97 CAD patients with 148 intermediate stenotic lesions were divided into two groups: current and former smokers (Smokers: n = 54), and those who had never smoked (Non-smokers: n = 43). Coronary physiology measurements were made following coronary angiography at rest and during hyperemia induced with intravenous adenosine triphosphate. If a patient had several intermediate lesions, the lesion producing the largest IMR value and minimum FFR(myo) and CFR(thermo) value was selected. Averaged over all patients, the FFR(myo), CFR(thermo), and IMR values were 0.86 ± 0.10, 2.66 ± 1.50, and 20.8 ± 10.7, respectively. There was no significant correlation between FFR(myo) and IMR. There were no significant differences between smokers and non-smokers in FFR(myo) value (median: 0.85 [IQR: 0.74-0.90] versus 0.87 [IQR: 0.83-0.90], P = 0.15) and CFR(thermo) value (median: 1.90 [IQR: 1.56-3.16] versus 2.10 [IQR: 1.50-2.67] U, P = 0.95). The IMR value was significantly greater in smokers (median: 24.2 [IQR: 16.8-32.5] U versus 18.5 [IQR: 15.4-27.0] U, P = 0.04). In multivariate analysis, smoking was an independent predictor of increased IMR. Smoking appears to have a detrimental effect on coronary microvascular function as measured by IMR.

Diagnostic significance of a small Q wave in precordial leads V(2) or V(3).

BACKGROUND: An abnormal Q wave is usually defined as an initial depression of the QRS complex having a duration of > or =40 ms and amplitude exceeding 25% of the following R wave in any contiguous leads on the 12-lead electrocardiogram (ECG). However, much smaller Q waves are sometimes recorded on the ECG. This study investigated the diagnostic value of the small Q wave recorded in precordial leads V(2) or V(3) on the ECG. METHODS: We investigated 807 consecutive patients who underwent coronary angiography. A small Q wave was defined as any negative deflection preceding the R wave in V(2) or V(3) with <40-ms duration and <0.5-mV amplitude, with or without a small (<0.1-mV) slurred, spiky fragmented initial QRS deflection before the Q wave (early fragmentation). ECG and coronary angiographic findings were analyzed. RESULTS: The small Q wave was present in 87 patients. Multiple logistic regression analysis revealed that presence of a small Q wave was a strong independent predictor of any coronary artery stenosis or left anterior descending artery (LAD) stenosis (odds ratio = 2.706, 2.902; P < 0.001, < 0.001, respectively). CONCLUSION: A small Q wave (<40-ms duration and <0.5-mV amplitude) in V(2) or V(3) with or without early fragmentation significantly predicted the presence of CAD and, especially, significant stenosis in the LAD.

Clinical course of arrhythmogenic right ventricular cardiomyopathy in the era of implantable cardioverter-defibrillators and radiofrequency catheter ablation.

This study investigated the clinical course of arrhythmogenic right ventricular cardiomyopathy (ARVC) patients and in particular evaluated the contribution of radiofrequency catheter ablation (RFCA) and an implantable cardioverter-defibrillator (ICD) to the treatment of ARVC. ARVC is a myocardial disorder and a cause of sudden cardiac death due to ventricular tachycardia (VT). Little is known about its prognosis in Japanese ARVC patients. Thirty-five ARVC patients were studied. Mean age of patients whose onset of ARVC was congestive heart failure (CHF) (66.0 +/- 4.0 years) was significantly higher than those whose onset was VT (44.5 +/- 14.8 years, P < 0.05). ARVC patients with CHF onset showed significantly higher death rates compared to those with VT onset. ICD treatment significantly reduced episodes of hospitalization due to VT (0.1 +/- 0.4 episodes) in comparison to treatment by RFCA (1.7 +/- 2.2 episodes, P < 0.03). RFCA treatment did not reduce recurrence of VT in the follow-up period. ICD therapy showed comparable mortality to RFCA treatment. The prognosis of ARVC with CHF onset is poor. ICD therapy significantly reduced hospitalization due to VT compared with RFCA treatment. ICD implantation in combination with medication may be a better treatment for ARVC.

Impending paradoxical cerebral embolism in a patient with atrial septal aneurysm.

There is increasing emphasis on the role of interatrial septal abnormalities, including patent foramen ovale and atrial septal aneurysm, in the genesis of stroke. However, a transseptal thrombus located in both atria is rarely visualized by echocardiography or other cardiac imaging techniques. It is also difficult to prove the mechanism of stroke in most clinical settings. In the present case of impending paradoxical cerebral embolism, the thrombus penetrating the atrial septal wall was visualized by transesophageal echocardiography.

Reversible left ventricular dysfunction "takotsubo" cardiomyopathy associated with hyperthyroidism.

Myocardial stunning with hyperthyroidism is rare. A 79-year old woman with hyperthyroidism was admitted to our hospital complaining of palpitations due to paroxysmal atrial fibrillation. An echocardiogram showed akinesis of the apical wall which was not observed 2 weeks before admission. Cardiac catheterization performed in the acute phase showed normal coronary arteries and no evidence of provocative spasms. The wall motion abnormality disappeared entirely after 1 week in hospital. We report a case of transient left ventricular dysfunction, so called "takotsubo" cardiomyopathy, associated with hyperthyroidism.

Giant organized thrombus in the left sinus of valsalva causing intermittent left coronary obstruction: an unusual case of acute myocardial infarction.

A 48-year-old Japanese man was admitted to hospital for acute myocardial infarction associated with a giant organized thrombus occupying the left sinus of Valsalva. Cardiac catheterization revealed no organic stenosis in either coronary artery, but left ventriculography and aortography showed a filling defect above the left coronary cusp. Transesophageal echocardiography was immediately performed and showed a round mass filling the left sinus of Valsalva. A solid, round mass approximately 2.5 cm in diameter was removed during emergency surgery and determined to be a thrombus on the basis of microscopic findings. This is the second report of a giant organized thrombus occupying the entire left sinus of Valsalva, obstructing the ostium of the left coronary artery intermittently, and leading to acute myocardial infarction.