Endogenous Adenosine May Be Related to Left Ventricular Dysfunction, Dilation, and Wall Thinning in Patients With Heart Disease.

BACKGROUND: The role of endogenous adenosine in cardiac patients is still unclear, so we investigated the relationship between the plasma adenosine concentration and left ventricular (LV) function, LV dilation and LV wall thinning in cardiac patients.Methods and Results:In 97 cardiac patients, with angina pectoris, old myocardial infarction, dilated or hypertrophic cardiomyopathy, and valvular heart disease, plasma adenosine concentrations were measured using the LC-MS/MS system, and the LV function, LV end-diastolic dimension (LVDd), LV posterior wall thickness (LVPWth), and interventricular septum thickness (IVSth) were assessed by echocardiography. The plasma adenosine concentration was significantly higher in patients with a LV ejection fraction (EF), an indicator of the LV systolic function, <47% compared with those with LVEF ≥47% (P=0.027). There was no difference between the plasma adenosine concentration and E/e', an indicator of LV diastolic function. The plasma adenosine concentration was significantly higher in patients with LVDd ≥50 mm than in those with LVDd <50 mm (P=0.030). The plasma adenosine concentration was inversely correlated with IVSth (P=0.003) and LVPWth (P=0.0007). The plasma adenosine concentration was significantly higher in patients with IVSth <8 mm than in those with IVSth ≥8 mm (P=0.015), and was significantly higher in patients with LVPWth <8 mm than in those with LVPWth ≥8 mm (P=0.020). CONCLUSIONS: Endogenous adenosine may be related to LV dysfunction, dilation, and wall thinning in cardiac patients.

Mobilized Muse Cells After Acute Myocardial Infarction Predict Cardiac Function and Remodeling in the Chronic Phase.

BACKGROUND: Multilineage differentiating stress-enduring (Muse) cells are SSEA3+and CD105+double-positive pluripotent-like stem cells. We aimed to examine the mobilization of Muse cells into peripheral blood after acute myocardial infarction (AMI) and their effects on left ventricular (LV) function and remodeling.Methods and Results:In 79 patients with AMI, 44 patients with coronary artery disease (CAD), and 64 normal subjects (Control), we measured the number of Muse cells in the peripheral blood by fluorescence-activated cell sorting. Muse cells were measured on days 0, 1, 7, 14, and 21 after AMI. Plasma sphingosine-1-phosphate (S1P) levels were measured. Cardiac echocardiography was performed in the acute (within 7 days) and chronic (6 months) phases of AMI. Muse cell number on day 1 was significantly higher in the AMI (276±137 cells/100 µL) than in the CAD (167±89 cells/100 µL) and Control (164±125 cells/100 µL) groups. Muse cell number peaked on day 1, and had gradually decreased on day 21. Muse cell number positively correlated with plasma S1P levels. Patients with a higher increase in the number of Muse cells in the peripheral blood but not those with a lower increase in number of Muse cells in the acute phase showed improved LV function and remodeling in the chronic phase. CONCLUSIONS: Endogenous Muse cells were mobilized into the peripheral blood after AMI. The number of Muse cells could be a predictor of prognosis in patients with AMI.

Investigation of the relationship between intradialytic hypotension during hemodialysis and serum syndecan-1 concentration.

Intradialytic hypotension and arrhythmias are complications of hemodialysis. They are associated with decreased intravascular volume due to reduced ultrafiltration volume, cardiac function, and arterial tone. The vascular endothelial glycocalyx, which exists on the surface of healthy vascular endothelial cells and maintains vascular permeability, has been suggested to be impaired by hemodialysis. This single-center retrospective study evaluated the association between syndecan-1, an endothelial glycocalyx dysfunction marker, and complications of hemodialysis. We enrolled 92 patients who underwent outpatient hemodialysis at Gifu Seiryu Hospital from April to July 2022 (346 hemodialysis sessions). The median duration and time of hemodialysis were 40 months and 4.1 h, respectively. Median serum syndecan-1 levels were 67.7 ng/mL before and 98.3 ng/mL after hemodialysis. Hemodialysis complications were noted in 68 sessions, all of which were hypotension. No correlation between pre-hemodialysis syndecan-1 levels and the incidence of complications was observed. However, a positive correlation between the amount of change in syndecan-1 levels before and after hemodialysis and the incidence of hemodialysis complications was noted. Conversely, syndecan-1 levels did not correlate with brain or atrial natriuretic peptides, suggesting that impairment of the vascular endothelial glycocalyx may be a possible cause of intradialytic hypotension and may be useful in preventing intradialytic hypotension.

Incessant Atrial Tachycardia Following Combination Chemotherapy with Cetuximab, Cisplatin and 5-Fluorouracil for Hypopharyngeal Cancer.

A 72-year-old man with stage IV hypopharyngeal cancer, who had been treated for three months with combination chemotherapy, was referred to our cardiology department for evaluation of transient palpitation. Combination therapy with cetuximab, cisplatin, and 5-fluorouracil per cycle had been administered intravenously for five cycles every three weeks for three months. After the admission due to slight palpitation and severe hypomagnesemia (Mg = 0.6 mmol/L), monitor ECG showed supraventricular tachycardia (SVT), which was incessantly sustained and ceased every few minutes. 12-lead ECG obtained during tachycardia demonstrated long RP' narrow QRS tachycardia. SVT was initially considered to be related to severe hypomagnesemia. However, it still occurred even after normalization of serum magnesium level. As the SVT was refractory to landiolol and verapamil, catheter ablation was performed a few days after the admission, revealing non-reentrant focal atrial tachycardia (AT) originating from the posterolateral region of the right atrium. Homogenization of the origin of the AT was then performed with radiofrequency, resulting in complete suppression of the AT. In the present case, the patient receiving the combination therapy of cetuximab, cisplatin, and 5-FU developed focal atrial tachycardia after chemotherapy, which was successfully treated with the radiofrequency catheter ablation.

In situ nuclear DNA methylation in dilated cardiomyopathy: an endomyocardial biopsy study.

AIMS: Although distinct DNA methylation patterns have been reported, its localization and roles remain to be defined in heart failure. We investigated the cellular and subcellular localization of DNA methylation and its pathophysiological significance in human failing hearts. METHODS AND RESULTS: Using left ventricular (LV) endomyocardial biopsy specimens from 75 patients with dilated cardiomyopathy (DCM; age: 58 ± 14 years old, %female: 32%) and 20 patients without heart failure (controls; age: 56 ± 17 years old, %female: 45%), we performed immunohistochemistry and immunoelectron microscopy for methylated DNA, 5-methylcytosine (5-mC). We next investigated possible relations of the incidence of 5-mC-positive (%5-mC+ ) cardiomyocytes with clinicopathological parameters. Immunopositivity for 5-mC was detected in the cardiomyocytes and other cell types. The %5-mC+ cardiomyocytes was significantly greater in DCM hearts than in controls (57 ± 13% in DCM vs. 25 ± 12% in controls, P < 0.0001). The localization of 5-mC immunopositivity in cardiomyocyte nuclei coincided well with that of heterochromatin, as confirmed by immunoelectron microscopy. Substantial DNA methylation was also observed in interstitial non-cardiomyocytes, but the incidences did not differ between control and DCM hearts (39 ± 7.9% in DCM vs. 41 ± 10% in controls, P = 0.4099). In DCM patients, the %5-mC+ cardiomyocytes showed a significant inverse correlation with LV functional parameters such as heart rate (r = 0.2391, P = 0.0388), end-diastolic pressure (r = 0.2397, P = 0.0397), and ejection fraction (r = -0.2917, P = 0.0111) and a positive correlation with LV dilatation (volume index at diastole; r = 0.2442, P = 0.0347; and volume index at systole; r = 0.3136, P = 0.0062) and LV hypertrophy (mass index; r = 0.2287, P = 0.0484)-that is, LV remodelling parameters. No significant correlations between DNA methylation and the histological parameters of the biopsies, including cardiomyocyte hypertrophy, fibrosis, and inflammatory cell infiltration, were noted. CONCLUSIONS: The present study revealed increased nuclear DNA methylation in cardiomyocytes, but not other cell types, from DCM hearts, with predominant localization in the heterochromatin. Its significant relations with LV functional and remodelling parameters imply a pathophysiological significance of DNA methylation in heart failure.

Efficacy of Acupuncture Treatment for Improving the Respiratory Status in Patients Receiving Prolonged Mechanical Ventilation in Intensive Care Units: A Retrospective Observational Study.

BACKGROUND AND OBJECTIVE: Patients in critical care settings often require prolonged mechanical ventilation (MV) therapy and, occasionally, they cannot be weaned from MV. The authors evaluated the efficacy of acupuncture treatment for improving the respiratory status and promoting successful weaning from prolonged MV in patients at intensive care units (ICUs). DESIGN: Retrospective observational study. SETTING: Gifu University Hospital, Gifu, Japan. SUBJECTS: The authors included 16 tracheostomized patients receiving MV for >21 days at the ICU of Gifu University Hospital, who underwent acupuncture therapy for improving their respiratory status. INTERVENTION: Acupuncture treatment was conducted in four sessions per week. OUTCOME MEASURES: The data of tidal volume (VT), respiratory rate (RR), heart rate (HR), oxygen saturation as measured by pulse oximetry (SpO2), dynamic lung compliance (Cdyn), rapid shallow breath index (RSBI; RR/VT) values before and immediately after acupuncture were extracted from the medical records. RESULTS: The median number of days on MV before acupuncture initiation was 31 days. VT and Cdyn were significantly increased immediately after acupuncture (all p < 0.001), whereas RR, HR, and RSBI were significantly decreased (all p < 0.05). Eleven patients were successfully weaned from MV after acupuncture initiation. In the weaning success group, VT and Cdyn were significantly increased (all p < 0.01), whereas RR, HR, and RSBI were significantly decreased (all p < 0.05) after acupuncture. Conversely, in the weaning failure group, these values were not changed significantly. The increase in Cdyn after acupuncture was larger in the weaning success group than in the weaning failure group (p < 0.05). CONCLUSION: Acupuncture treatment might have beneficial effects on the respiratory status of ICU patients receiving MV and may help in weaning from prolonged MV. Further large prospective cohort studies are warranted.

Acupuncture and Traditional Herbal Medicine Therapy Prevent Deliriumin Patients with Cardiovascular Disease in Intensive Care Units.

The aim of this study was to determine the effect of combination therapy consisting of acupuncture and traditional herbal medicine (Kampo medicine) for reducing the incidence rate of delirium in patients with cardiovascular (CV) disease in ICUs. Twenty-nine patients who had been urgently admitted to the ICU in the control period were treated with conventional intensive care. Thirty patients in the treatment period received conventional therapy plus a combination therapy consisting of acupuncture and herbal medicine. Acupuncture treatment was performed once a day, and the herbal formula was administered orally three times a day during the first week of the ICU stay. The standard acupuncture points were GV20, Ex-HN3, HT7, LI4, Liv3, and KI3, and the main herbal preparation was Kamikihito. The incident rates of delirium, assessed using the confusion assessment method for ICU, in the treatment and control period were compared. The incidence rate of delirium was significantly lower in the treatment group than in the control group (6.6% vs. 37.9%, [Formula: see text]). Moreover, sedative drugs and non-pharmacological approaches against aggressive behavior of patients who were delirious were used less in the treatment group than in the control group. No serious adverse events were observed in the treatment group. Combination therapy consisting of acupuncture and herbal medicine was found to be effective in lowering the incidence of delirium in patients with CV disease in ICUs. Further studies with a large sample size and parallel randomized controlled design would be required to establish the effects of this therapy.

Continuous intravenous infusion of nicorandil for 4 hours before and 24 hours after percutaneous coronary intervention protects against contrast-induced nephropathy in patients with poor renal function.

BACKGROUND: We conducted a prospective randomized trial to assess the protective effect of continuous intravenous infusion of nicorandil against contrast-induced nephropathy (CIN) in patients with poor renal function. METHODS AND RESULTS: We randomly assigned 213 patients who would subsequently undergo elective percutaneous coronary intervention (PCI) and who had a high serum cystatin C level to a saline group (n=107) or a nicorandil group (n=106, nicorandil infused in addition to saline for 4h before and 24h after PCI). There were no significant differences in baseline characteristics between the two groups. However, the average percent increases in serum creatinine and cystatin C following PCI were significantly smaller in the nicorandil group than the saline group. Likewise, the average percent decline in the estimated glomerular filtration rate was smaller in the nicorandil group. Correspondingly, the incidence of CIN was dramatically lower in the nicorandil group than the saline group (2.0% vs. 10.7%, p<0.02). Univariate regression analysis revealed nicorandil treatment to be the only significant predictor of CIN development (odds ratio: 0.173, 95% confidence interval: 0.037-0.812, p=0.026). CONCLUSIONS: Nicorandil strongly prevents CIN in patients with poor renal function undergoing PCI.

An autopsy report of acute myocardial infarction with hypertrophic obstructive cardiomyopathy-like heart.

An 84-year-old woman, who was followed up as hypertrophic obstructive cardiomyopathy (HOCM) in a local hospital, was transferred to our center because of anterior chest pain and diagnosed with acute myocardial infarction (MI). Coronary angiography showed total occlusion of the mid-left anterior descending, and flow was restored after endovascular thrombectomy. An autopsy was performed after she died on hospital day 6. At autopsy, there was no significant stenosis in this vessel and the absence of plaque rupture was confirmed. Likewise, it was unclear asymmetric hypertrophy at autopsy, it could not deny that a sigmoid deformity of the basal septum occurs in elderly patients and can mimic the asymmetric septal hypertrophy of hypertrophic cardiomyopathy. MI was thought to be caused by coronary spasm or squeezing in HOCM-like heart. Therefore, it may be necessary antithrombosis therapy in HOCM-like patients with no history of paroxysmal atrial fibrillation.

Traditional thermal therapy with indirect moxibustion decreases renal arterial resistive index.

OBJECTIVE: To evaluate the immediate effects of indirect moxibustion, a traditional local thermal therapy, on renal hemodynamics by using Doppler ultrasonography (US). DESIGN: Prospective observational study of postintervention changes in several variables. SETTING: Gifu University Hospital, Gifu, Japan. PARTICIPANTS: Eleven healthy persons (7 men and 4 women; mean age±standard deviation, 32.6±5.7 years) were enrolled. INTERVENTION: Indirect moxibustion was applied for 4 minutes to bilateral lower back acupuncture points (BL23). Each participant received 3 successive treatments. OUTCOME MEASURES: The main outcome measurement was resistive index (RI) in the renal segmental arteries. Blood flow variables, including RI, were measured for 6 renal segmental arteries by Doppler US at rest (baseline), immediately after completion of moxibustion (post 1), and 10 minutes later (post 2). Participants were monitored for adverse events during the intervention. RESULTS: The mean RI was 0.578±0.037 at baseline, 0.546±0.027 at post 1, and 0.547±0.032 at post 2. RI decreased significantly between post 1 and baseline (95% confidence interval [CI], -0.053 to -0.011; p=0.003) and between post 2 and baseline (95% CI, -0.052 to -0.009; p=0.005). No adverse events, such as burns, were observed. CONCLUSION: This study of the short-term effects of indirect moxibustion on renal hemodynamics in healthy persons showed that renal vascular resistance was reduced after the therapy.

Sleep apnoea induces cardiac electrical instability assessed by T-wave alternans in patients with congestive heart failure.

AIMS: To assess the involvement of sleep apnoea in nocturnal sudden cardiac death (SCD) by evaluating cardiac electrical instability using T-wave alternans (TWA), a risk marker for lethal cardiac arrhythmias, and severity of sleep apnoea in congestive heart failure (CHF) patients. METHODS AND RESULTS: A total of 40 CHF patients simultaneously underwent overnight simplified respiratory polygraphy and 24 h continuous electrocardiography. Peak TWA during both daytime and nighttime were calculated by the modified moving average method. The patients were divided into two groups; 30 patients with daytime predominant TWA (whose peak TWA was higher during daytime than during nighttime) and 10 with nighttime predominant. Apnoea-hypopnoea index (AHI) was significantly higher in patients with nighttime predominant TWA than in those with daytime predominant (35.9 +/- 8.1 vs. 23.9 +/- 14.4 events/h, P = 0.02), and was an independent predictor of nighttime predominant TWA (odds ratio, 1.08; 95% confidence interval, 1.01-1.16; P = 0.03). Moreover, peak TWA during the night was correlated positively with AHI (P < 0.001), and AHI was an independent determinant of nocturnal TWA value (r(2) = 0.27, P = 0.009). CONCLUSION: In CHF patients, sleep apnoea induces cardiac electrical instability manifested as TWA, reflecting increased risk of nocturnal SCD. Moreover, some CHF patients with sleep apnoea exhibit nighttime predominant TWA. Therefore, TWA should also be evaluated during the night.