Induced Pluripotent Stem Cell-Derived Cardiomyocytes Therapy for Ischemic Heart Disease in Animal Model: A Meta-Analysis.

Ischemic heart disease (IHD) poses a significant challenge in cardiovascular health, with current treatments showing limited success. Induced pluripotent derived-cardiomyocyte (iPSC-CM) therapy within regenerative medicine offers potential for IHD patients, although its clinical impacts remain uncertain. This study utilizes meta-analysis to assess iPSC-CM outcomes in terms of efficacy and safety in IHD animal model studies. A meta-analysis encompassing PUBMED, ScienceDirect, Web of Science, and the Cochrane Library databases, from inception until October 2023, investigated iPSC therapy effects on cardiac function and safety outcomes. Among 51 eligible studies involving 1012 animals, despite substantial heterogeneity, the iPSC-CM transplantation improved left ventricular ejection fraction (LVEF) by 8.23% (95% CI, 7.15 to 9.32%; p < 0.001) compared to control groups. Additionally, cell-based treatment reduced the left ventricle fibrosis area and showed a tendency to reduce left ventricular end-systolic volume (LVESV) and end-diastolic volume (LVEDV). No significant differences emerged in mortality and arrhythmia risk between iPSC-CM treatment and control groups. In conclusion, this meta-analysis indicates iPSC-CM therapy's promise as a safe and beneficial intervention for enhancing heart function in IHD. However, due to observed heterogeneity, the efficacy of this treatment must be further explored through large randomized controlled trials based on rigorous research design.

In vivo tracking transplanted cardiomyocytes derived from human induced pluripotent stem cells using nuclear medicine imaging.

Introduction: Transplantation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) is a promising treatment for heart failure. Information on long-term cell engraftment after transplantation is clinically important. However, clinically applicable evaluation methods have not yet been established. Methods: In this study, to noninvasively assess transplanted cell engraftment, human SLC5A5, which encodes a sodium/iodide symporter (NIS) that transports radioactive tracers such as 125I, 18F-tetrafluoroborate (TFB), and 99mTc-pertechnetate (99mTcO4-), was transduced into human induced pluripotent stem cells (iPSCs), and nuclear medicine imaging was used to track engrafted human iPSC-CMs. Results: To evaluate the pluripotency of NIS-expressing human iPSCs, they were subcutaneously transplanted into immunodeficient rats. Teratomas were detected by 99mTcO4- single photon emission computed tomography (SPECT/CT) imaging. NIS expression and the uptake ability of 125I were maintained in purified human iPSC-CMs. NIS-expressing human iPSC-CMs transplanted into immunodeficient rats could be detected over time using 99mTcO4- SPECT/CT imaging. Unexpectedly, NIS expression affected cell proliferation of human iPSCs and iPSC-derived cells. Discussion: Such functionally designed iPSC-CMs have potential clinical applications as a noninvasive method of grafted cell evaluation, but further studies are needed to determine the effects of NIS transduction on cellular characteristics and functions.

Microcalcification and 99mTc-Pyrophosphate Uptake without Increased Bone Metabolism in Cardiac Tissue from Patients with Transthyretin Cardiac Amyloidosis.

Transthyretin cardiac amyloidosis (ATTR-CA) is characterized by high 99mTc-labeled bone tracer uptake in the heart. However, the mechanism of bone tracer uptake into the heart remains controversial. Since bone tracer uptake into metastatic bone tumors is thought to be associated with increased bone metabolism, we examined 99mTc-pyrophosphate (PYP) scintigraphy findings, endomyocardial biopsy (EMB) tissue findings, and the expression of bone metabolism-related genes in the EMB tissues in patients with ATTR-CA, amyloid light-chain cardiac amyloidosis (AL-CA), and noncardiac amyloidosis (non-CA) in this study. The uptake of 99mTc-PYP in the heart was significantly higher in the ATTR-CA patients than in the AL-CA and non-CA patients. A higher percentage of ATTR-CA EMB tissue showed von Kossa-positive microparticles: ATTR-CA, 62%; AL-CA, 33%; and non-CA, 0%. Calcified microparticles were identified using transmission electron microscopy. However, none of the osteogenic marker genes, osteoclastic marker genes, or phosphate/pyrophosphate-related genes were upregulated in the EMB samples from ATTR-CA patients compared to those from AL-CA and non-CA patients. These results suggest that active calcification-promoting mechanisms are not involved in the microcalcification observed in the heart in ATTR-CA. The mechanisms explaining bone tracer uptake in the heart, which is stronger than that in the ribs, require further investigation.

Innovative clinical pathway shortened the length of hospital stay and prevented readmission in patients with acute decompensated heart failure.

BACKGROUND: With the rapidly aging population in Japan, the number of patients hospitalized for acute decompensated heart failure (ADHF) is increasing. Mitoyo General Hospital created an innovative clinical pathway (CP) for promoting early discharge in patients with ADHF. Major points of the CP were as follows: using tolvaptan as a standard therapy, completing the acute therapies within three days, and starting cardiac rehabilitation from the second day after admission. METHODS: We collected data for patients with ADHF who were admitted to our hospital before introduction of the CP (non-CP group) (April 2014-July 2015) and after introduction of the CP (CP group) (August 2015-July 2019). We investigated the impact of the CP on the length of hospital stay (LOHS) and readmission after discharge. RESULTS: After screening, 593 patients were enrolled in this study. After performing propensity score matching, 129 patients in the non-CP group and 129 patients in the CP group were analyzed. LOHS of patients in the CP group was significantly shorter than that of patients in the non-CP group [20 (14-28) days vs 12 (8-21) days] (p < 0.001) without an increase in mortality during hospitalization or an increase in the rate of readmission due to ADHF within 30 days. Use of the CP was an independent negative factor contributing to LOHS for patients with ADHF, even after adjustment of other factors including the use of tolvaptan (p < 0.001). The CP significantly decreased the proportion of patients readmitted to hospitals due to ADHF within 6 months [n = 32 (27%) vs n = 18 (15%), p = 0.026] and 1 year [n = 40 (34%) vs n = 23 (19%), p = 0.009] after discharge compared to the proportion in the non-CP group. CONCLUSIONS: The CP significantly reduced the LOHS of patients without increasing the in-hospital mortality and it also reduced the risk of readmission in the mid-term and long-term.

Favorable effect of catheter ablation on nocturnal hypertension in patients with paroxysmal atrial fibrillation.

OBJECTIVES: The current study was performed to determine whether pulmonary vein isolation (PVI) improves nocturnal hypertension in patients with paroxysmal atrial fibrillation (PAF). BACKGROUND: Abnormal night-time blood pressure (BP) fluctuation is a risk factor for atrial fibrillation. Imbalance of autonomic nervous function is a risk factor common to both of these abnormalities. PVI can reportedly modify the autonomic nervous function balance in patients with atrial fibrillation. METHODS: The study population comprised 50 consecutive patients (mean age, 69.8 ±â€Š7.5 years; 35.0% male) with PAF scheduled for PVI. Both 24-h ambulatory BP monitoring and heart rate variability analysis were performed before and at 3 months after PVI. RESULTS: Patients were classified into two groups according to the presence of nocturnal BP dipping before PVI: the normal dipping group (n = 27) and the nondipping group (n = 23). The low-frequency spectrum power and the ratio of low-frequency spectrum power to high-frequency spectrum power (low-frequency spectrum/high-frequency spectrum) were higher in the nondipping than the normal dipping group (low-frequency spectrum: 219.9 ±â€Š210.2 vs. 92.7 ±â€Š50.5 ms, respectively, P = 0.03; low-frequency spectrum/high-frequency spectrum: 1.8 ±â€Š1.9 vs. 0.9 ±â€Š0.8, respectively, P = 0.05). In the nondipping group, the elevated night-time BP disappeared in eight (35%) patients at 3 months after PVI, which was associated with an increase in high-frequency spectrum power. These patients did not develop atrial fibrillation recurrence during follow-up (mean, 568 ±â€Š218 days). CONCLUSION: Among patients with PAF, the nondipping group showed greater sympathetic activity (higher low-frequency spectrum power and low-frequency spectrum/high-frequency spectrum) than the dipping group. Restoration of BP dipping after PVI is associated with increased parasympathetic activity (higher high-frequency spectrum power) and reduced recurrence of arrhythmic events.

Rembrandt's Maria Bockenolle has a butterfly rash and digital deformities: overlapping syndrome of rheumatoid arthritis and systemic lupus erythematosus.

Rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) are the most common autoimmune disorders, although they each have very different pathophysiology. In general, RA is considered to be a Th1-mediated disease, while SLE is a Th2-mediated disease. Thus, their overlapping, in so called "rhupus", is a rare condition. In Rembrandt van Rijn's (1606-1669) portrait of the middle-aged Maria Bockenolle, we have what may be the earliest depiction of a case of rhupus syndrome: the coexistence of a butterfly rash and digital deformities. This suggests the possible historical importance of an RA epidemic which took place in the early 17th century.