Hitoshi Minamiguchi

Heterogeneous arterial healing in patients following paclitaxel-eluting stent implantation: comparison with sirolimus-eluting stents.

OBJECTIVES We angioscopically compared paclitaxel-eluting stents (PES) and sirolimus-eluting stents (SES) to explore differences in arterial healing. BACKGROUND Drug-eluting stents may demonstrate different arterial healing processes. METHODS Angioscopy was performed 9 +/- 2 months after 30 PES and 36 SES were implanted initially in the native coronary artery. Heterogeneity of the neointimal coverage (NIC) as well as the dominant grade was examined. Neointimal coverage was defined as follows: grade 0 = fully visible struts; grade 1 = struts bulged into the lumen, but covered; grade 2 = embedded, but translucent struts; grade 3 = invisible struts. Heterogeneity was judged when the NIC grade variation >or=1. Thrombi and yellow plaques (YP) were also explored. RESULTS In-stent late loss (0.44 +/- 0.44 mm vs. 0.13 +/- 0.33 mm; p < 0.0001) and dominant NIC grade (1.8 +/- 1.1 vs. 1.3 +/- 0.7; p = 0.02) were greater in PES than in SES. Of PES, 48% showed the heterogeneity of 1 grade; 26% showed that of 2 grades. Of SES, 53% showed homogeneous coverage; the remaining SES showed the heterogeneity of 1 grade; and 72% showed dominant grade 1. Thrombi were more common in PES than in SES (43% vs. 19%; p = 0.04). Both stents commonly revealed YP (83% vs. 78%; p = 0.76). CONCLUSIONS NIC was more heterogeneous in PES, associated with a higher incidence of thrombi. Homogeneous NIC may be an important factor for competent arterial healing.

Usefulness of transient elastography for noninvasive and reliable estimation of right-sided filling pressure in heart failure.

Accurate noninvasive assessment of right atrial pressure (RAP) is important for volume management in patients with heart failure (HF). Transient elastography is a noninvasive and reliable method to assess liver stiffness (LS). We investigated the value of LS for evaluation of RAP in patients with HF without structural liver disease. We measured LS using transient elastography (Fibroscan) in 31 patients undergoing right-sided cardiac catheterization (test group). The relation between LS and RAP found in the test group was used to derive the best-fit model to predict RAP. The applicability of the model was then tested in a validation group of 49 additional patients. There was an excellent correlation between LS and RAP in the test group (r = 0.95, p <0.0001; RAP = -5.8 + 6.7 × ln [LS]). Natural log transformation (ln) of LS provided the regression equation to predict RAP. When the equation model derived from the test group was applied to the validation group, predicted RAP correlated excellently with actual RAP (r = 0.90, p <0.0001). The receiver operating characteristic curve analyses in the test group showed that LS favorably compared with echocardiography for detecting RAP >10 mm Hg (area under the curve 0.958 vs 0.800, respectively, p = 0.047). In the validation group, LS with a cut-off value of 10.6 kPa for identifying RAP >10 mm Hg had a higher sensitivity and accuracy (p = 0.046 and p = 0.049, respectively) than echocardiography. In conclusion, LS may offer an accurate noninvasive diagnostic method to assess RAP in patients with HF.

A Case of Interstitial Pneumonitis Associated with Natural α-lnterferon Therapy for Myelofibrosis

A 55-year-old man with myelofibrosis was treated with natural alpha-interferon with a good hematologic response. Initially, he had anemia, leukocytosis, thrombocytosis and hepatospleomegaly. A bone marrow biopsy showed replacement with fibrosis with an increase in megakaryocytes. Natural alpha-interferon (alpha-IFN) was started at a dose of 3 x 10(6) units/day. The leukocyte and platelet counts gradually normalized, and the liver and spleen decreased in size. However, the patient complained of a dry cough and dyspnea on the 61st treatment day, when the accumulated dose of alpha-IFN treatment had reached 1.8 x 10(8) units. He subsequently developed acute respiratory failure (PaO2 < 60 mm Hg) with bilateral lung infiltrations, suggesting the occurrence of interstitial pneumonitis associated with alpha-interferon therapy. Immediately, the alpha-interferon was discontinued and high-dose methylprednisolone (1.5 g/day) was administered for 3 days. This treatment was followed by oral prednisone therapy. Steroid therapy brought about gradual improvement as suggested by a repeat radiograph. Since high levels of fibrogenic cytokines, such as PDGF and TGF-beta, have been reported in patients with myelofibrosis, it is necessary to pay attention to interstitial pneumonia as a complication in alpha-IFN therapy for myelofibrosis.

Haematopoietic action of flt3 ligand on cord blood‐derived CD34‐positive cells expressing different levels of flt3 or c‐kit tyrosine kinase receptor: comparison with stem cell factor

We compared the effect of human flt3 ligand (FL) and stem cell factor (SCF) on cord blood (CB)‐derived CD34+ cells expressing different levels of flt3 or c‐kit tyrosine kinase (TK) receptor in clonal cell culture. The c‐kit receptor was expressed by 58.5±16.7% of CB CD34+ cells (n = 19), in which c‐kithigh, c‐kitlow and c‐kit‐ cell populations could be identified. In contrast, the flt3 receptor (FR) was weakly expressed on 58.6±8.3% (n = 9) of CB CD34+ cells. FL+erythropoietin (Epo) failed to support erythroid burst (BFU–E) formation by any subpopulation of CD34+ cells. However, SCF+Epo supported BFU–E and erythrocyte‐containing mixed (CFU–mix) colony formation from all subpopulations. Interestingly, FL markedly augmented CFU–mix colony formation supported by interleukin (IL)‐ 3+Epo when CD34+c‐kitlow or CD34+FR+ cells were used as the target. On the other hand, SCF significantly enhanced CFU‐mix colony formation supported by IL‐3+Epo when CD34+c‐kithigh or low and CD34+FR+ cells were used. The replating potential of CFU–mix supported by IL‐3 + Epo + FL was greater when CD34+c‐kitlow or CD34+FR+ cells were used. When the CD34+c‐kitlow cells were used, the number of lineages expressed in secondary cultures of CFU–mix colonies derived from primary cultures containing IL‐3 + Epo+FL or SCF was significantly larger than when the primary cultures contained IL‐3+Epo. Furthermore, the number of long‐term culture‐initiating cells found in CD34+FR+ cells was larger than that in FR‐ cells. CB‐derived CD34+c‐kitlow cells represent a less mature population than c‐kithigh cells, as reported previously. Therefore, these results indicate that both FL and SCF can act on primitive multipotential progenitors. However, it is still uncertain whether CB‐derived CD34+FR+ cells are less mature than CD34+FR‐ cells.

Clinical Impact of Ventricular Tachycardia and/or Fibrillation During the Acute Phase of Acute Myocardial Infarction on In-Hospital and 5-Year Mortality Rates in the Percutaneous Coronary Intervention Era

BACKGROUND The aim of this study was to investigate the prognostic impact of acute-phase ventricular tachycardia and fibrillation (VT/VF) on ST-segment elevation myocardial infarction (STEMI) patients in the percutaneous coronary intervention (PCI) era. METHODSANDRESULTS Using the database of the Osaka Acute Coronary Insufficiency Study (OACIS), we studied 4,283 consecutive patients with STEMI who were hospitalized within 12 h of STEMI onset and underwent emergency PCI. Acute-phase VT/VF, defined as ≥3 consecutive ventricular premature complexes and/or VF within the 1st week of hospitalization, occurred in 997 (23.3%) patients. In-hospital mortality risk was significantly higher in patients with acute-phase VT/VF than inthose without (14.6% vs. 4.3%, adjusted hazard ratio (HR) 1.83, P=0.0013). Among patients discharged alive, 5-year mortality rates were comparable between patients with and without acute-phase VT/VF. Subgroup analysis showed that acute-phase VT/VF was associated with increased 5-year mortality after discharge in high-risk patients (GRACE Risk Score ≥115; adjusted HR 1.60, P=0.043), but not in intermediate- or low-risk patients. CONCLUSIONS Even in the PCI era, acute-phase VT/VF was associated with higher in-hospital deaths of STEMI patients. However, the 5-year prognostic impact of acute-phase VT/VF was limited to high-risk patients. (Circ J 2016; 80: 1539-1547).

Impact of atrial fibrillation ablation on cardiac sympathetic nervous system in patients with and without heart failure

BACKGROUND/OBJECTIVES Catheter ablation of atrial fibrillation (AF) might influence the cardiac autonomic nervous system. To investigate the impact of catheter ablation on the sympathetic nervous function in AF patients with and without heart failure (HF) using cardiac iodine-123-metaiodobenzylguanidine ((123)I-mIBG) scintigraphy, and the association of this effect with AF recurrence. METHODS Forty consecutive patients (median age, 65 (54-69) years; male, 29) with paroxysmal (n=22) and persistent (n=18) AF who were scheduled for ablation were enrolled. Twelve (30%) of these patients also exhibited either stable HF, defined as an ejection fraction <40%, or a history of symptomatic HF. (123)I-mIBG scintigraphy was performed at baseline and 3months post-ablation. The heart-to-mediastinum ratio of (123)I-mIBG uptake at 15min (H/M15min) and 240min (H/M240min), as well as the washout rate (WR) were measured. RESULTS During an 11±4-month follow-up, AF recurrence was observed in 8 (20%) patients receiving no antiarrhythmic drugs. Patients with HF had a tendency toward a lower baseline H/M15min (1.91±0.06 vs. 2.05±0.04, p=0.07), significantly lower H/M240min (1.88±0.22 vs. 2.14±0.28, p=0.008), and higher WR (40.3±9.0 vs. 32.3±7.4, p=0.007). Post-ablation, WR decreased in patients with HF (40.2±8.5 to 29.0±8.9, p=0.02) but slightly increased in those without (32.0±7.4 to 34.6±10.3, p=0.04). WR post-ablation independently predicted AF recurrence (adjusted hazard ratio=1.14 for 1 percentage point increase in the WR, 95% coincidence interval=1.02-1.34, p=0.02). CONCLUSIONS AF ablation restores sympathetic nervous system status via attenuation of excessive adrenergic tone in HF patients. Elevated sympathetic nervous tone 3months post-ablation was a reliable predictor of AF recurrence.

Management of infection during chemotherapy for acute leukemia in Japan: a nationwide questionnaire-based survey by the Japan Adult Leukemia Study Group

PurposeWe performed a nationwide questionnaire-based survey to evaluate the current clinical practices of infectious complications during chemotherapy for acute leukemia in Japan.MethodsWe e-mailed a questionnaire to member institutions of the Japan Adult Leukemia Study Group in September, 2013. The questionnaire consisted of 50 multiple-choice questions covering therapeutic environment, antimicrobial prophylaxis, screening test during neutropenia, empirical therapy for febrile neutropenia, and the use of granulocyte-colony stimulating factor. The results were compared to those of previous surveys conducted in 2001 and 2007, and also to the recommendations described in the guidelines.ResultsUsable responses were received from 141 out of 222 (63.5%) institutions. Chemotherapy for acute myeloid leukemia was performed in protective environment in 90% of the institutions, which increased compared to previous survey (76%). Fluoroquinolones and fluconazole were the most commonly used antimicrobial agents for antibacterial and antifungal prophylaxis, followed by sulfamethoxazole-trimethoprim and itraconazole, respectively. In empirical therapy for febrile neutropenia, monotherapy with β-lactum antibiotics was the first-line therapy in most of the institutions. While empirical antifungal therapy was adopted for persistent fever in more than half of the institutions, preemptive/presumptive therapy was also used in approximately 40% of the institutions. Most of the clinicians were reluctant to use granulocyte-colony stimulating factor routinely in chemotherapy for acute myeloid leukemia.ConclusionsThis study clarified the current clinical practices of infectious complications during chemotherapy for acute leukemia and would provide important information for the development of a suitable guideline in Japan.

Switching from carvedilol to bisoprolol ameliorates adverse effects in heart failure patients with dizziness or hypotension

BACKGROUND Treatment with carvedilol is an established primary therapy for patients with heart failure (HF). However, its most common adverse effects, dizziness and hypotension, often discourage continuation or dosage increase. The aim of this study was to examine whether switching to bisoprolol from carvedilol would help to avoid adverse symptoms and signs related to carvedilol administration. METHODS AND SUBJECTS Data were retrospectively collected from 23 patients with HF [age 57±18 years, left ventricular ejection fraction (LVEF) 33±15%] who could not increase the dosage of carvedilol because of dizziness or hypotension, defined as systolic blood pressure<90 mmHg. Before and immediately after, and 6 months after switching to bisoprolol, we examined symptoms, vital signs, laboratory data, and New York Heart Association functional class. Furthermore, left ventricular (LV) dimension and ejection fraction (EF) were evaluated in 19 patients using echocardiography. RESULTS All 13 patients with dizziness (100%) and 9 of 16 with hypotension (56%) were relieved of adverse symptoms or signs. The mean dose of carvedilol before switching was 5.60±3.43 mg. Immediately after the switch, the mean dose of bisoprolol was 1.84±1.08 mg and then increased to 3.13±1.74 mg after 6 months (p<0.01). At 6-month follow-up examinations, LV function determined by LVEF was significantly improved, which was accompanied by increased exercise tolerance. CONCLUSION Switching from carvedilol to bisoprolol may help with continuation of β-blocker treatment as well as dosage increase in HF patients with adverse symptoms or signs, allowing them to reach the target dose.

A CT number-controlling system for reproducibility of intracoronary CT number on follow-up coronary CT angiography

BACKGROUND Coronary computed tomography angiography (CCTA) may be useful for noninvasive follow-up; however, evaluation of coronary stenosis and CT number of plaque may be inaccurate under different vessel enhancement of contrast media. We examined the reproducibility of the CT number of repeat CCTA using our original CT number-controlling system (CTN-CS), which selects contrast level by a multiple regression equation using body surface area and peak CT number and peak time on timing bolus and during CCTA. METHODS AND RESULTS One hundred seventy-two patients who underwent serial CCTA were prospectively and randomly assigned to 3 groups. In the first group, Group A, the amount of contrast for the second CCTA was determined by CTN-CS to match the intracoronary CT number of the first CCTA. In Group B, each patient received the same amount of intravenous contrast in both CCTA examinations. In Group C, 0.7 mL/mg body weight (BW) of contrast medium (350 mgI/mL) was used for baseline and follow-up CCTAs. The regression of repeated CCTAs was the best in Group A (r=0.85, p<0.001) vs. Group B (r=0.52, p<0.001), and Group C (r=0.61, p<0.001). The absolute difference between intracoronary CT numbers of the second and first CCTA was the lowest in Group A (24.8 ± 21.8HU), followed by Group B (37.6 ± 26.2 HU; p<0.05) and Group C (46.5 ± 34.4HU; p<0.001). CONCLUSIONS Using CTN-CS, the difference of intracoronary CT numbers of the second and first CCTA was the smallest when compared to CCTAs using the same contrast volumes or constant volumes per body weight.

Superior Rhythm Discrimination With the SmartShock Technology Algorithm ― Results of the Implantable Defibrillator With Enhanced Features and Settings for Reduction of Inaccurate Detection (DEFENSE) Trial ―

BACKGROUND Shocks delivered by implanted anti-tachyarrhythmia devices, even when appropriate, lower the quality of life and survival. The new SmartShock Technology®(SST) discrimination algorithm was developed to prevent the delivery of inappropriate shock. This prospective, multicenter, observational study compared the rate of inaccurate detection of ventricular tachyarrhythmia using the SST vs. a conventional discrimination algorithm.Methods and Results:Recipients of implantable cardioverter defibrillators (ICD) or cardiac resynchronization therapy defibrillators (CRT-D) equipped with the SST algorithm were enrolled and followed up every 6 months. The tachycardia detection rate was set at ≥150 beats/min with the SST algorithm. The primary endpoint was the time to first inaccurate detection of ventricular tachycardia (VT) with conventional vs. the SST discrimination algorithm, up to 2 years of follow-up. Between March 2012 and September 2013, 185 patients (mean age, 64.0±14.9 years; men, 74%; secondary prevention indication, 49.5%) were enrolled at 14 Japanese medical centers. Inaccurate detection was observed in 32 patients (17.6%) with the conventional, vs. in 19 patients (10.4%) with the SST algorithm. SST significantly lowered the rate of inaccurate detection by dual chamber devices (HR, 0.50; 95% CI: 0.263-0.950; P=0.034). CONCLUSIONS Compared with previous algorithms, the SST discrimination algorithm significantly lowered the rate of inaccurate detection of VT in recipients of dual-chamber ICD or CRT-D.