Current differentiation protocols for human induced pluripotent stem cells (hiPSCs) produce heterogeneous cardiomyocytes (CMs). Although chamber-specific CM selection using cell surface antigens ...enhances biomedical applications, a cell surface marker that accurately distinguishes between hiPSC-derived atrial CMs (ACMs) and ventricular CMs (VCMs) has not yet been identified. We have developed an approach for obtaining functional hiPSC-ACMs and -VCMs based on CD151 expression. For ACM differentiation, we found that ACMs are enriched in the CD151
population and that CD151 expression is correlated with the expression of Notch4 and its ligands. Furthermore, Notch signaling inhibition followed by selecting the CD151
population during atrial differentiation leads to the highly efficient generation of ACMs as evidenced by gene expression and electrophysiology. In contrast, for VCM differentiation, VCMs exhibiting a ventricular-related gene signature and uniform action potentials are enriched in the CD151
population. Our findings enable the production of high-quality ACMs and VCMs appropriate for hiPSC-derived chamber-specific disease models and other applications.
ObjectiveThis study aims to investigate the time-dependent prognostic utility of two fibrosis markers representing organ fibrogenesis (N-terminal propeptide of procollagen III (PIIINP) and type IV ...collagen 7S (P4NP 7S)) in patients with acute heart failure (HF).Methods390 patients with acute HF were dichotomised based on the median value of fibrosis markers at discharge. The primary outcome measure was a composite of cardiac death and HF hospitalisation.ResultsP4NP 7S significantly declined during hospitalisation, whereas PIIINP did not. The cumulative 90-day and 365-day incidence of the primary outcome measure was 16.6% vs 16.0% (p=0.42) and 33.3% vs 28.4% (p=0.34) in the patients with high versus low PIIINP; 19.9% vs 13.0% (p=0.04) and 32.3% vs 29.0% (p=0.34) in the patients with high and low P4NP 7S, respectively. After adjusting for confounders, high P4NP 7S correlated with significant excess risk relative to low P4NP 7S for both 90-day and 365-day primary outcome measure (adjusted HR, 1.50; 95% CI, 1.02 to 2.21; p=0.04 and adjusted HR, 1.89; 95% CI, 1.11 to 3.26; p=0.02, respectively), which was driven by significant association of high P4NP 7S with higher incidence of HF hospitalisation. Furthermore, P4NP 7S exhibited an additive value to conventional prognostic factors for predicting 90-day outcome (p=0.038 for net reclassification improvement; p=0.0068 for integrated discrimination improvement). High PIIINP did not correlate with significant excess risk for both 90-day and 365-day outcome.ConclusionsThis study suggests a possible role of P4NP 7S in the risk stratification of patients with acute HF.
Caffeine has been reported as a cause of cardiac arrest after massive overdose. Here, we report the case of a patient with caffeine intoxication, which can cause fatal dysrhythmias and severe ...hypokalemia. They were successfully treated with extracorporeal membrane oxygenation (ECMO).
A 43-year-old woman with a history of bipolar disorder presented to the emergency department after suicidal drug ingestion (caffeine and amitriptyline). Immediately after arrival, she experienced multiple episodes of ventricular fibrillation with severe hypokalemia requiring cardiopulmonary resuscitation and medical therapy. However, conventional treatment was not successful. We instituted ECMO early during resuscitation because prolonged hypokalemia refractory to aggressive potassium replacement precluded the use of antidysrhythmic medications for refractory circulatory compromise with ventricular fibrillation. The use of ECMO provided time to correct hypokalemia (19.3 g potassium) and reduce the caffeine level with hemodialysis. Although she had sustained cardiac arrest, she recovered fully and was discharged home.
Our case indicates the potential effectiveness of ECMO in severely poisoned patients with fatal dysrhythmias. ECMO could provide time for removal of toxic drugs and correction of electrolyte abnormalities.
Background Landiolol is often used for urgent management of rapid heart rate (HR) in patients with atrial fibrillation/flutter (AF/AFL) in Japan. A multivariate adjusted analysis showed that ...paroxysmal AF/AFL (odds ratio OR, 2.95; 95% confidence interval CI, 1.03-9.36; p=0.04), systolic blood pressure (SBP) at the time of landiolol administration (OR, 1.02; 95% CI, 1.00-1.04; p=0.02), left ventricular ejection fraction (LVEF) (OR, 1.04; 95% CI, 1.00-1.08; p=0.03), and the use of oral be-ta blocker prior to the administration of landiolol (OR, 0.23; 95% CI, 0.07-0.66; p=0.006) were independent predictors of the effectiveness of landiolol for urgent management of rapid HR in patients with AF/AFL.
...the carperitide group showed significant reduction in a composite of all-cause death or rehospitalization for HF (adjusted HR, 0.62; 95% confidence interval, 0.41-0.93; P=0.02). Conclusion In the ...treatment of AHF with moderate to severe pulmonary congestion, carperitide can be associated with more effective decongestion in the short term and better prognosis in the long term.
Hemodynamic disturbance in heart failure (HF) induces extra-cardiac organ injury. Atrial fibrillation (AF) is common in patients with HF. The relationship between AF and organ injury in HF remains ...unclear. We investigated the relationship between AF and the liver fibrosis marker, type IV collagen 7S (P4NP 7S) in patients with HF.
From a pooled dataset of 3 observational cohorts of hospitalized HF, 720 patients in whom P4NP 7S was measured before discharge were included. Median P4NP 7S were 5.1, 5.3, and 6.2 ng/mL in the sinus rhythm (SR) (n = 368), paroxysmal AF (n = 67), and persistent AF (n = 285) groups, respectively (P < 0.001). In the multiple linear regression analysis, the significant association with P4NP 7S was found for persistent AF (P < 0.001). The cumulative 1-year incidence of the primary composite endpoint of cardiac death and HF hospitalization were 27.6, 24.1, and 34.5% in the SR, paroxysmal AF, and persistent AF groups, respectively (Log-rank P = 0.07) and 25.3 and 34.5% in the low (below median) and high P4NP 7S groups, respectively (Log-rank P = 0.005). The adjusted risks of persistent AF versus SR and high P4NP 7S versus low P4NP 7S for the primary endpoint were 1.38 (95% confidence interval 1.02–1.89) and 1.52 (1.14–2.03), respectively. When patients were divided based on a combination of AF and P4NP 7S, concomitant persistent AF and high P4NP 7S portended a dismal prognosis.
AF is associated with an increase in the liver fibrosis marker. Co-presence of persistent AF and P4NP 7S may portend adverse clinical outcomes.
•Persistent atrial fibrillation (AF) was associated with an increased liver fibrosis.•Both persistent AF and high type IV collagen 7S (P4NP 7S) portends adverse outcomes.•Concomitant high P4NP 7S and persistent AF portends very poor prognosis.•P4NP 7S may facilitate the risk stratification of patients with persistent AF.
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