Sarcoidosis is a systemic granulomatous disease of unknown aetiology. The frequency of cardiac involvement (cardiac sarcoidosis (CS)) varies in the different geographical regions, but it has been ...reported that it is an absolutely important prognostic factor in this disease. Complete atrioventricular block is the most common, and ventricular tachycardia/ventricular fibrillation the second most common arrhythmia in this disease, both of which are associated with cardiac sudden death. Diagnosing CS is sometimes difficult because of the non-specific ECG and echocardiographic findings, and CS is sometimes misdiagnosed as dilated cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy or an idiopathic ventricular aneurysm, and therefore, endomyocardial biopsy is important, but has a low sensitivity. Another problem is the recognition of isolated types of CS. Recently, MRI and (18)F-fluorodeoxyglucose positron emission tomography have been demonstrated to be useful tools for the non-invasive diagnosis of CS as well as therapeutic evaluation tools, but are still unsatisfactory. Treatment of CS is usually done by corticosteroid therapy to control inflammation, prevent fibrosis and protect from any deterioration of the cardiac function, but the long-term outcome is still in debate. Despite the advancement of non-pharmacological approaches for CS (pacing, defibrillators and catheter ablation) to improve the prognosis, there are still many issues remaining to resolve diagnosing and managing CS. Here, we attempt a review of the clinical evidence, with special focus on the current understanding of this disease and showing the current strategies and remaining problems of diagnosing and managing CS.
Background:An atrial fibrillation (AF) risk score for a non-Western general population has not been established.Methods and Results:A total of 6,898 participants (30–79 years old) initially free of ...AF have been prospectively followed for incident AF since 1989. AF was diagnosed when AF or atrial flutter was present on ECG at a biannual health examination; was indicated as a current illness; or was in the medical records during follow-up. Cox proportional hazard ratios were analyzed after adjusting for cardiovascular risk factors at baseline. During the 95,180 person-years of follow-up, 311 incident AF events occurred. We developed a scoring system for each risk factor as follows: 0/−5, 3/0, 7/5, and 9/9 points for men/women in their 30 s–40 s, 50 s, 60 s, and 70 s, respectively; 2 points for systolic hypertension, overweight, excessive drinking, or coronary artery disease; 1 point for current smoking; −1 point for moderate non-high-density lipoprotein-cholesterol; 4 points for arrhythmia; and 8, 6, and 2 points for subjects with cardiac murmur in their 30 s–40 s, 50 s, and 60 s, respectively (C-statistic 0.749; 95% confidence interval, 0.724−0.774). Individuals with score ≤2, 10–11, or ≥16 points had, respectively, ≤1%, 9%, and 27% observed probability of developing AF in 10 years.Conclusions:We developed a 10-year risk score for incident AF using traditional risk factors that are easily obtained in routine outpatient clinics/health examinations without ECG.
Laboratory investigations on admission found an estimated glomerular filtration rate (eGFR) of 21·4 mL/min/1·73m2 (normal >90) and a serum B-type natriuretic peptide (BNP) concentration of 263 pg/mL ...(normal <18·4), indicating possible damage to the kidneys and heart; additional tests and examinations—including an echocardiogram, and brain and adrenal CTs—were normal, thereby ruling out any cerebral or cardiovascular emergencies that may have caused the raised blood pressure. After 90 days of treatment, the flow-mediated dilation was 7·5%, indicating significant improvement (figure 2; appendix). ...the urinary albumin-to-creatinine ratio—measured to complement assessment of vascular endothelial damage—showed a significant decrease to 44·7 mg/g (normal <30); on admission the ratio had been 411·6 mg/g. Malignant hypertension is a term used for patients with elevated blood pressure and multiple complications; hypertensive crisis describes patients with systolic blood pressure >180 mm Hg and diastolic >120 mm Hg.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Establishment of a biological pacemaker is expected to solve the persisting problems of a mechanical pacemaker including the problems of battery life and electromagnetic interference. Enhancement of ...the funny current (If) flowing through hyperpolarization-activated cyclic nucleotide-gated (HCN) channels and attenuation of the inward rectifier K+ current (IK1) flowing through inward rectifier potassium (Kir) channels are essential for generation of a biological pacemaker. Therefore, we generated HCN4-overexpressing mouse embryonic stem cells (mESCs) and induced cardiomyocytes that originally show poor IK1 currents, and we investigated whether the HCN4-overexpressing mESC-derived cardiomyocytes (mESC-CMs) function as a biological pacemaker in vitro.
The rabbit Hcn4 gene was transfected into mESCs, and stable clones were selected. mESC-CMs were generated via embryoid bodies and purified under serum/glucose-free and lactate-supplemented conditions. Approximately 90% of the purified cells were troponin I-positive by immunostaining. In mESC-CMs, expression level of the Kcnj2 gene encoding Kir2.1, which is essential for generation of IK1 currents that are responsible for stabilizing the resting membrane potential, was lower than that in an adult mouse ventricle. HCN4-overexpressing mESC-CMs expressed about a 3-times higher level of the Hcn4 gene than did non-overexpressing mESC-CMs. Expression of the Cacna1h gene, which encodes T-type calcium channel and generates diastolic depolarization in the sinoatrial node, was also confirmed. Additionally, genes required for impulse conduction including Connexin40, Connexin43, and Connexin45 genes, which encode connexins forming gap junctions, and the Scn5a gene, which encodes sodium channels, are expressed in the cells. HCN4-overexpressing mESC-CMs showed significantly larger If currents and more rapid spontaneous beating than did non-overexpressing mESC-CMs. The beating rate of HCN4-overexpressing mESC-CMs responded to ivabradine, an If inhibitor, and to isoproterenol, a beta-adrenergic receptor agonist. Co-culture of human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) with aggregates composed of mESC-CMs resulted in synchronized contraction of the cells. The beating rate of hiPSC-CMs co-cultured with aggregates of HCN4-overexpressing mESC-CMs was significantly higher than that of non-treated hiPSC-CMs and that of hiPSC-CMs co-cultured with aggregates of non-overexpressing mESC-CMs.
We generated HCN4-overexpresssing mESC-CMs expressing genes required for impulse conduction, showing rapid spontaneous beating, responding to an If inhibitor and beta-adrenergic receptor agonist, and having pacing ability in an in vitro co-culture system with other excitable cells. The results indicated that these cells could be applied to a biological pacemaker.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background: Atrial fibrillation (AF) is the most diagnosed arrhythmia in clinical settings. The fatty liver index (FLI) is a marker of liver steatosis with potential cardiovascular implications. This ...study investigated whether FLI could predict the risk of AF.Methods and Results: We used data from the Suita Study, a Japanese population-based prospective cohort study. A total of 2,346 men and 3,543 women, aged 30–84 years, without prevalent AF were included and followed up. The diagnosis of AF was established during follow-up using electrocardiograms, hospital records, and death certificates. FLI was assessed during a baseline health checkup. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for incident AF per FLI quintile and log-transformed FLI. Within a median 14.5 years of follow-up, 142 men and 105 women developed AF. Compared with women in the third (middle) FLI quintile, women in the first (lowest), fourth, and fifth (highest) quintiles showed a higher risk of AF, with multivariable-adjusted HRs of 2.37 (95% CI 1.06–5.31), 2.60 (95% CI 1.30–5.17), and 2.04 (95% CI 1.00–4.18), respectively. No corresponding associations were observed in men. The change in log-transformed FLI was not associated with the risk of AF in either sex.Conclusions: A U-shaped association between FLI and AF risk was detected in Japanese women. FLI could be a screening tool to detect women at high risk of developing AF.
This study aimed to determine the usefulness of the combination of several electrocardiographic markers on risk assessment of ventricular fibrillation (VF) in patients with Brugada syndrome (BrS).
...Detection of high-/low-risk BrS patients using a noninvasive method is an important issue in the clinical setting. Several electrocardiographic markers related to depolarization and repolarization abnormalities have been reported, but the relationship and usefulness of these parameters in VF events are unclear.
Baseline characteristics of 246 consecutive patients (236 men; mean age, 47.6 ± 13.6 years) with a Brugada-type electrocardiogram, including 13 patients with a history of VF and 40 patients with a history of syncope episodes, were retrospectively analyzed. During the mean follow-up period of 45.1 months, VF in 23 patients and sudden cardiac death (SCD) in 1 patient were observed. Clinical/genetic and electrocardiographic parameters were compared with VF/SCD events.
On univariate analysis, a history of VF and syncope episodes, paroxysmal atrial fibrillation, spontaneous type 1 pattern in the precordial leads, and electrocardiographic markers of depolarization abnormalities (QRS duration ≥120 ms, and fragmented QRS f-QRS) and those of repolarization abnormalities (inferolateral early repolarization ER pattern and QT prolongation) were associated with later cardiac events. On multivariable analysis, a history of VF and syncope episodes, inferolateral ER pattern, and f-QRS were independent predictors of documented VF and SCD (odds ratios: 19.61, 28.57, 2.87, and 5.21, respectively; p < 0.05). Kaplan-Meier curves showed that the presence/absence of inferolateral ER and f-QRS predicted a worse/better prognosis (log-rank test, p < 0.01).
The combination of depolarization and repolarization abnormalities in BrS is associated with later VF events. The combination of these abnormalities is useful for detecting high- and low-risk BrS patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background: The incidence and prevalence of atrial fibrillation (AF) are increasing. The white blood cell (WBC) count is an indicator of systemic inflammation and is related to increased ...cardiovascular disease risk. Using data from the Suita Study, we investigated the association between WBC count and AF risk in the general Japanese population.Methods and Results: This prospective cohort study included 6,884 people, aged 30–84 years, with no baseline AF. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for AF incidence by WBC count quintile. Within a median follow-up period of 14.6 years, 312 AF cases were diagnosed. Compared with the lowest WBC count quintile, the highest quintile was associated with an increased AF risk (HR 1.57; 95% CI 1.07–2.29). The association was more pronounced among women than men (HR 2.16 95% CI 1.10–4.26 and 1.55 95% CI 0.99–2.44, respectively; P interaction=0.07), and among current than non-smokers (HR 4.66 95% CI 1.89–11.50 and 1.61 95% CI 1.01–2.57, respectively; P interaction=0.20). For each 1.0×109-cells/L increment in WBC count, AF risk increased by 9% in men (9% in non-smokers, 10% in current smokers) and 20% in women (13% in non-smokers, 32% in current smokers).Conclusions: A higher WBC count was positively associated with an elevated AF risk in the general Japanese population, especially in women who smoked.
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