Implications of multiple late gadolinium enhancement lesions on the frequency of left ventricular reverse remodeling and prognosis in patients with non-ischemic cardiomyopathy.

BACKGROUND: Non-ischemic cardiomyopathy (NICM) is a heterogeneous disease, and its prognosis varies. Although late gadolinium enhancement (LGE)-cardiovascular magnetic resonance (CMR) demonstrates a linear pattern in the mid-wall of the septum or multiple LGE lesions in patients with NICM, the therapeutic response and prognosis of multiple LGE lesions have not been elucidated. This study aimed to investigate the frequency of left ventricular (LV) reverse remodeling (LVRR) and prognosis in patients with NICM who have multiple LGE lesions. METHODS: This single-center retrospective study included 101 consecutive patients with NICM who were divided into 3 groups according to LGE-CMR results: patients without LGE (no LGE group = 48 patients), patients with a typical mid-wall LGE pattern (n = 29 patients), and patients with multiple LGE lesions (n = 24 patients). LVRR was defined as an increase in LV ejection fraction (LVEF) ≥ 10 % and a final value of LVEF > 35 %, which was accompanied by a decrease in LV end-systolic volume ≥ 15 % at 12-month follow-up using echocardiography. The frequency of composite cardiac events, defined as sudden cardiac death (SCD), aborted SCD (non-fatal ventricular fibrillation, sustained ventricular tachycardia, or adequate implantable cardioverter-defibrillator therapies), and heart failure death or hospitalization for worsening heart failure, were summarized and compared between the groups. RESULTS: Among the 3 groups, the frequency of LVRR was significantly lower in the multiple lesions group than in the no LGE and mid-wall groups (no LGE vs. mid-wall vs. multiple lesions: 49 % vs. 52 % vs. 19 %, p = 0.03). There were 24 composite cardiac events among the patients: 2 in patients without LGE (hospitalization for worsening heart failure; 2), 7 in patients of the mid-wall group (SCD; 1, aborted SCD; 1 and hospitalization for worsening heart failure; 5), and 15 in patients of the multiple lesions group (SCD; 1, aborted SCD; 8 and hospitalization for worsening heart failure; 6). The multiple LGE lesions was an independent predictor of composite cardiac events (hazard ratio: 11.40 [95 % confidence intervals: 1.49-92.01], p = 0.020). CONCLUSIONS: Patients with multiple LGE lesions have a higher risk of cardiac events and poorer LVRR. The LGE pattern may be useful for an improved risk stratification in patients with NICM.

Coronary artery lumen complexity as a new marker for refractory symptoms in patients with vasospastic angina.

Refractory angina is an independent predictor of adverse events in patients with vasospastic angina (VSA). The aim of this study was to investigate the relationship between coronary lumen complexity and refractory symptoms in patients with VSA. Seventeen patients with VSA underwent optical coherence tomography. The patients were divided into the refractory VSA group (n = 9) and the stable VSA group (n = 8). A shoreline development index was used to assess the coronary artery lumen complexity. Shear stress was estimated using a computational fluid dynamics model. No difference was observed in the baseline characteristics between the two groups. The refractory VSA group showed the higher shoreline development index (refractory VSA 1.042 [1.017-1.188] vs stable VSA 1.003 [1.006-1.025], p = 0.036), and higher maximum medial thickness (refractory VSA 184 ± 17 µm vs stable VSA 148 ± 31 µm, p = 0.017), and higher maximum shear stress (refractory VSA 14.5 [12.1-18.8] Pa vs stable VSA 5.6 [3.0-10.5] Pa, p = 0.003). The shoreline development index positively correlates with shear stress (R2 = 0.46, P = 0.004). Increased medial thickness of the coronary arteries provokes lumen complexity and high shear stress, which might cause refractory symptoms in patients with VSA. The shoreline index could serve as a marker for irritability of the medial layer of coronary arteries and symptoms.

A biodegradable microneedle sheet for intracorporeal topical hemostasis.

Management of bleeding is critical for improving patient outcomes. While various hemostatic products are used in daily practice, technical improvement is still needed. To addresses this problem, we newly developed a microneedle hemostatic sheet based on microneedle technology. We demonstrated the unique features of this microneedle hemostatic sheet, including reduced hemostatic time, biodegradable polymer composition that allows intracorporeal use without increasing infectious risk incorporation of microneedles to fix the sheet to the wound even on the left ventricular wall of a swine while beating, and a mesh structure with flexibility comparable to that of bonding surgical tape and sufficient rigidity to penetrate human aorta tissue and swine left ventricular wall. One potential application of the microneedle hemostatic sheet is intracorporeal topical hemostasis for parenchymatous organs, large vessels, and heart wall during trauma or surgery, in addition to new, widespread applications.

Effect of coronary artery bypass grafting on blood pressure response to head-up tilting.

Blood pressure response to head-up tilt (HUT) in 7 healthy subjects and 9 patients before and after coronary artery bypass grafting (CABG) was measured during supine and 15-min 60° HUT. Stroke volume (SV) and ejection fraction (EF) were assessed by echocardiography. Baseline mean arterial pressure (MAP) and heart rate (HR) in patients before CABG were similar to healthy subjects. MAP in patients decreased by 6 (4-9) mmHg [median (1st-3rd quartiles)] during 7-12 mmHg of HUT with decreased cardiac output (CO = SV × HR) while HR remained unchanged. MAP in healthy subjects remained unchanged during HUT with increased HR. Body weight decreased by 3.5 (2.5-3.7) kg and MAP decreased by 6 (2-13) mmHg during the last 3-min HUT while HR increased after CABG. Decreases in SV and CO during HUT disappeared after CABG. Blood pressure decreased during HUT in patients before and after CABG regardless of HR response.

Efficient cleavage of DNA oligonucleotides by a non-FokI-type zinc finger nuclease containing one His4-type finger domain derived from the first finger domain of Sp1.

In this study, we sought to improve the hydrolytic activity of a His4-type single finger domain (f2), which was previously derived from the second finger domain (f2') of the Sp1 zinc finger protein (Sp1wt), which has 3 tandem finger domains (f1', f2', and f3'). To this end, 2 His4-type single finger domains were generated by mutating 2 Cys residues participating in Zn(II) coordination with the His residues in the first (f1') and third finger (f3') domains of Sp1wt. Circular dichroism spectroscopy results showed that the first and second His4-type zinc finger domains (f1 and f2) adopted folded ßßα structures in the presence of Zn(II), but that the third His4-type zinc finger domain (f3) did not. Non-FokI-type zinc finger nucleases containing 3 or 4 finger domains were also prepared by combining a His4-type zinc finger domain with the Sp1wt scaffold. We studied their DNA-binding abilities and hydrolytic activities against DNA oligonucleotides by performing gel-mobility-shift assays. The results showed that f1 had higher hydrolytic activity for a DNA oligonucleotide with a GC box (5'-GGG GCG GGG-3'), compared with that of f2, although both His4-type single finger domains had similar DNA-binding affinities. The difference in the hydrolytic activity between f1 and f2 was ascribed not only to the zinc coordinate structure, but also to its folding structure and the stability of finger domain.

The origin of progesterone in blood when a bacterial solution is infused into the uterus of rats.

PURPOSE: The infusion of a bacterial solution into the uterus of rats raises the progesterone (P4) concentration in serum and extends diestrus. To understand the origin of the P4, we investigated the change in the P4 concentration of seven groups of rats for 5 days after the infusion of a bacterial solution. METHODS: The rats were divided into 7 treatment groups as follows: OvxBac, AdxBac, Ovx, Adx, LapBac, Lap, and Cont. In OvxBac, rats received both ovariectomy and bacterial inoculation into their uterus. In AdxBac, rats received both adrenalectomy and bacterial inoculation into their uterus. In Ovx, rats received only ovariectomy. In Adx, rats received only adrenalectomy. In LapBac, rats received only bacterial inoculation into their uterus. In Lap, rats received only laparotomy. In Cont, rats did not receive any treatment and acted as controls. RESULTS: The P4 concentration in all treatment groups was higher than in Cont on day 1 (the day following operation) and day 2. In Lap and LapBac, the P4 concentration was high on day 1 (>30 ng/mL) and maintained that value until day 2. In Adx and AdxBac, the P4 concentration was average on day 1 (approximately 25 ng/mL) and increased on day 2 to a value close to that of LapBac and Lap. In OvxBac, although the P4 concentration increased slightly on day 1 and day 2, it reached 22.5 ± 7.5 ng/mL on day 4. In AdxBac and LapBac, the P4 concentration on day 4 tended to be high. CONCLUSION: These results suggest that P4 is initially secreted from the ovaries and the adrenals in response to the surgical stress of laparotomy, and is later secreted from the adrenals due to the inflammatory reaction of the uterus.