Cheyne-Stokes Breathing as a Predictive Indicator of Heart Failure in Patients With Obstructive Sleep Apnea; A Retrospective Case Control Study Using Continuous Positive Airway Pressure Remote Monitoring Data.

OBJECTIVE: We conducted a retrospective case control study to examine whether remote monitoring of Cheyne-Stokes breathing (CSB) was useful for predicting the onset of heart failure (HF) in patients with obstructive sleep apnea (OSA) on continuous positive airway pressure (CPAP). METHODS: Among patients with OSA treated at our hospital, 33 patients with HF that occurred between July 2014 and May 2021 [11 patients with acute HF (AHF); 22 patients with chronic HF (CHF) exacerbation] were included in the HF group. Of the 618 stable patients, 149 patients with a 30-days average CSB rate (CSB%) ≧1% were included in the non-HF control group. The chronologic change of CSB% were compared among the AHF, CHF and Control groups. Furthermore, of the 149 patients in the non-HF control group, 44 patients were matched for CSB%, body mass index, and sex in a ratio of 1:2 to 22 patients with CHF. The average cycle length (CL) of CSB was compared among three groups: CHF in stable period (CHF-stable group), CHF in exacerbation period (CHF-exacerbation group), and control group. In addition, according to the status of HF, receiver operating characteristic (ROC) curves were generated to determine the optimal cut-off points for variation of CSB% and CL. RESULTS: Chronological change in CSB% among the three groups was significantly different. Standard deviation of CSB% (SD CSB%) before onset HF was significantly higher in both the AHF and CHF groups than in the control group. The CL of CSB was significantly longer in the CHF group than in the control group and was longer during the exacerbation period than during the stable period. The optimal cut-off value of CL that could differentiate patients with and without the onset of HF was 68.9 s. CONCLUSION: The HF group demonstrated greater CSB variations and longer CL than the non-HF control group. Furthermore, the CL was longer during the exacerbation period of HF even in the same patient. These results suggest that remote monitoring of CPAP device data for CSB variations and CL might allow early prediction of the onset and exacerbation of HF.

Blood glucose dynamics during sleep in patients with obstructive sleep apnea and normal glucose tolerance: effects of CPAP therapy.

PURPOSE: Glycemic variability (GV) and hypoglycemia during nighttime are presumed to be associated with fatal bradycardia. The aim of this prospective study was to evaluate blood glucose dynamics during sleep in patients with obstructive sleep apnea syndrome (OSA) and normal glucose tolerance. METHODS: Patients with OSA and no diabetes who underwent type 1 overnight polysomnography from December 2018 to May 2020 participated in this study. GV was evaluated in all participants for 14 days using a flash glucose monitoring device. Correlations were examined between GV indexes and indexes related to sleep breathing disorders, the effects of treatment with continuous positive airway pressure (CPAP) on these GV indexes, and the characteristics of glucose dynamics in different OSA subtypes classified by sleep stage. RESULTS: Among 42 patients with OSA and no diabetes, the standard deviation of GV during sleep correlated significantly with sleep time spent with oxygen saturation <90% (r=0.591, p=0.008). High blood glucose index during sleep correlated significantly with stage N1% (r=0.491, p=0.032) and negatively with stage N2% (r=-0.479, p=0.038). High blood glucose index correlated significantly with sleep time spent with oxygen saturation <90% (r=0.640, p=0.003). The rapid eye movement-related OSA group had a higher incidence of hypoglycemia. One-week with CPAP treatment significantly improved GV during sleep, standard deviation of GV (from 12.1 to 9.0 mg/dL, p<0.001), and high blood glucose index (from 0.7 to 0.4, p=0.006). CONCLUSIONS: To evaluate GV during sleep in patients with OSA may be useful for clinical risk management. CPAP treatment for 1 week may have an improving GV and high blood glucose index. CLINICAL TRIAL REGISTRATION: UMIN000038489 2019/11/04, UMIN 000025433 2016/12/27.

Periodic breathing in patients with stable obstructive sleep apnea on long-term continuous positive airway pressure treatment: a retrospective study using CPAP remote monitoring data.

PURPOSE: The purpose of this study was to investigate the rate of periodic breathing (PB) and factors associated with the emergence or persistence of PB in patients with obstructive sleep apnea (OSA) by continuous positive airway pressure (CPAP) remote monitoring data. METHODS: This was a retrospective cohort study on 775 patients who had used the same model CPAP machine for at least 1 year as of September 1, 2020. The data were analyzed online using the dedicated analysis system. Using exporter software, average apnea/hypopnea index (AHI), average central apnea index (CAI), and average the rate of PB time (PB%) were cited. RESULTS: Among 618 patients analyzed (age 61.7 ± 12.2 years, male 89%, BMI 27.2 ± 4.9), the average duration of CPAP use was 7.5 ± 4.0 years. The median PB% in stable patients was low at 0.32%, and only 149 patients (24%) had a PB% above 1%. Multiple regression analysis of factors for the development of PB showed that the most important factor was atrial fibrillation (Af) with a coefficient of 0.693 (95% CI; 0.536 to 0.851), followed by QRS duration with a coefficient of 0.445 (95% CI; 0.304 to 0.586), followed by history of heart failure, male sex, comorbid hypertension, obesity, and age. The average PB% for paroxysmal Af was significantly lower than that for persistent and permanent Af. CONCLUSIONS: The median PB% in stable patients on CPAP treatment was low at 0.32%, with only 24% of patients having PB% ≥ 1%. Persistent Af and an increase in QRS duration were found to be important predictors of increased PB%. CLINICAL TRIAL REGISTRATION: UMIN000042555 2021/01/01.

Advanced atrioventricular block induced by obstructive sleep apnea before oxygen desaturation.

We report a patient with transient advanced atrioventricular (AV) block induced by obstructive sleep apnea (OSA). This 54-year-old man was diagnosed as having severe OSA and AV block with ventricular asystole for more than 6 s during overnight polysomnography, which occurred just from the onset of OSA before oxygen desaturation had occurred. An electrophysiological study revealed normal AV conduction system function and normal His-Purkinje system function. The resolution of OSA with continuous positive airway pressure therapy improved the advanced AV block. Therefore, the bradyarrhythmia was determined to be an OSA-induced AV block that occurred before oxygen desaturation.

[A case of CD56 positive T-cell lymphoma originating from mediastinal lymph nodes].

The patient, a 63-year-old man was admitted to our hospital with complaints of high-grade fever and left chest pain. The chest X-ray film taken on admission showed the presence of pleural effusion. The chest CT scan revealed left mediastinal enlargement. Examination of the pleural effusion showed a high concentration of adenosine deaminase (ADA) and the cytological examination showed no malignancy. We diagnosed pleuritis tuberculosa. His general condition worsened in spite of anti-tuberculosis therapy and soluble interleukin-2 receptor (sIL-2R) was elevated. The video-assisted thoracoscopic biopsy was negative. Soon after that the lymph nodes from the left supraclavicular region to the mediastinum became swollen. The diagnosis of peripheral T-cell lymphoma, unspecified (WHO classification) with CD56 expression, was established based on the results of lymph node biopsy and pleural effusion cytology. He was treated with cyclophosphamide/doxorubicin/vincristine/prednisolone (CHOP) chemotherapy. Since two courses of chemotherapy were not effective we changed to carboplatin/ifosfamide/ etoposide/dexamethasone (DeVIC) chemotherapy. His condition improved and a complete response was obtained. In conclusion, the presence of a high level of ADA in the pleural effusion and resistance to anti-tuberculosis therapy should suggest a malignant lymphoma.

[A case of tuberculous peritonitis].

We report a case of a 73-year-old man with tuberculous peritonitis. He had sought treatment at a clinic near his house for his fever and abdominal distension. Massive ascites were found and he was referred to our hospital. The endoscopy and abdominal CT scan performed on admission revealed no abnormal findings except the massive ascites. Mycobacterium tuberculosis (MT) DNA was detected in the ascitic fluid by polymerase chain reaction (PCR) and ascitic adenosine deaminase (ADA) activity was 127.6 U/l. He was diagnosed as tuberculous peritonitis and transferred to the Department of Respiratory Medicine. A chest CT scan showed predominant right pleural effusion with no other abnormal findings in bilateral lung fields. His sputum were all positive by smear acid-fast staining, MT DNA and culture on MT. His final diagnosis was tuberculous peritonitis, pulmonary tuberculosis, and tuberculous pleuritis. Treatment was started by anti-tuberculosis drugs with combined use of isoniazid, rifampicin, ethambutol, and pyrazinamide. The therapy was continued for 6 months. The culture for MT (Mycobacteria Growth Indicator Tube) converted to negative after 2 weeks of treatment and the C-reactive protein level became normal after a month. The pleural effusion and ascites disappeared after 2 and 3 months, respectively. Tuberculous peritonitis is a relatively rare disease, however when we encounter unexplained ascites, MT PCR and the measurement of ADA should be done considering a rapid diagnosis of tuberculous peritonitis, before invasive diagnostic laparoscopy.

[A case of Kartagener's syndrome].

This case describes a 57-year-old woman in whom situs inversus had been noted at her birth. She had bronchial asthma and bilateral sinusitis during her childhood. She married and experienced childbirth. In December 2003, she was admitted to our Division complaining of wheezing, expectoration and dyspnea on effort. Bronciectasis was visualized on chest X-ray and CT. Electron microscopic examination of the nasal cavity epithelium and bronchial epithelial cilia revealed a deficit of bilateral dynein arms. These findings, helped establish a diagnosis of Kartagener's syndrome, which is characterized by primary ciliary dyskinesia. The restrictive and obstructive pulmonary dysfunction with increase of residual volume in the lung function tests and diffuse centrilobular small nodules with hyperinflation on chest CT were consistent with the findings of diffuse panbronchilitis (DPB) and suggested extended obliterative peripheral airway disease. Clarithromycin which is highly effective for DPB failed to prevent the aggravation of airway infection, arousing the concern about the progression into chronic respiratory failure.

[A case of secondary pulmonary cryptococcosis complicating diabetes mellitus].

In this case, a 65-year-old man complained of fever and productive cough while being treated for diabetes mellitus at the outpatient clinic. His chest CT scan revealed multiple infiltrative lesions in both the right and left lower pulmonary lobes. He was therefore given an antibiotic on suspicion of having bacterial pneumonia, and he also received nutritional instruction in relation to diabetes mellitus, and remission resulted. However, he could not maintain sufficient glycemic control thereafter, and his pulmonary lesions persisted. Because his lesions changed into cavitied multiple nodular lesions, as seen on a chest CT scan, a transbronchial lung biopsy was performed. Histopathological examination of the biopsy specimen demonstrated Cryptococcus organisms, and the Cryptococcus antigen titer was high, which led to a diagnosis of pulmonary cryptococcosis. After oral treatment with fluconazole for 1 year and 4 months, only a small nodule in the right lower lobe and a funicular lesion in the left lower lobe remained on a chest CT scan, and the patient had neither subjective symptoms nor evidence of inflammation, although he still had a positive antigen titer for Cryptococcus. Thus, the treatment was terminated. Improvement of the clinical symptoms and of the laboratory and radiological findings demonstrated the therapeutic efficacy of this treatment.

Assessment of fatty acid metabolism in taxan-induced myocardial damage with iodine-123 BMIPP SPECT: comparative study with myocardial perfusion, left ventricular function, and histopathological findings.

UNLABELLED: We investigated myocardial fatty acid metabolism in taxan-induced myocardial damage in patients with advanced lung cancer. PATIENTS AND METHODS: Twenty-five patients with non-small-cell lung cancer were treated with taxan combined with carboplatin intravenously for three cycles. Myocardial SPECT imaging using 99mTc-methoxyisobutyl isonitrile (MIBI) and 123I-15-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) was performed successively before and after chemotherapy. Regional uptake scores of BMIPP and MIBI were visually assessed and total uptake scores and the number of abnormal segments were calculated. Left ventricular ejection fraction (LVEF) was obtained by first-pass radionuclide angiocardiography using MIBI. Postmortem pathological examination was performed in 5 patients. RESULTS: Total BMIPP uptake scores after chemotherapy were significantly lower than those before chemotherapy (23.4 +/- 3.4 vs. 26.6 +/- 0.8; p < 0.001). Mean LVEF showed a significant decrease after chemotherapy. Of the 25 patients, 4 exhibited a decrease in LVEF of more than 10%, 1 had a decrease in LVEF to below 50%, and 1 developed congestive heart failure. These 6 patients had significant decreases in total BMIPP uptake scores and increases in the number of abnormal segments as compared with the other 19 patients. Histopathological examination of myocardial tissue showed interstitial edema and disarrayed myocardial cells. CONCLUSION: Taxan impairs myocardial fatty acid metabolism. 123I-BMIPP myocardial SPECT is useful for evaluating the cardiotoxicity induced by taxan.

[A case of true pulmonary carcinosarcoma].

The patient was a 47-year-old man who had visited a nearby physician with a chief complaint of bloody sputum. This patient underwent partial resection of the left upper lobe including a tumor adjacent to a huge bulla revealed by a plain chest radiograph. The resected tumor was composed of adenocarcinomatous and sarcomatous components, including partially-differentiated chondrosarcoma and rhabdomyosarcoma. The diagnosis was therefore true pulmonary carcinosarcoma. The sarcoma component recurred in the remaining part of the left lung. This recurrent lesion was surgically unresectable, but was regionally controlled with radiotherapy and bronchial arterial infusion of anticancer agents. However, distant metastases occurred to the brain, liver, and small intestine, and digestive tract bleeding also occurred. Nevertheless, chemotherapy, linac radiosurgery, percutaneous radiofrequency ablation, and partial small intestinal resection combined with rectal resection were performed. At autopsy, a metastatic lesion was also detected in the pancreas. Liver metastatic lesions were determined to be the adenocarcinomatous component, and the other recurrent or metastatic lesions, except for those in the brain, were all composed of poorly-differentiated sarcomatous tissue.

Differences in fatty acid metabolic disorder between ischemic myocardium and doxorubicin-induced myocardial damage: assessment using BMIPP dynamic SPECT with analysis by the Rutland method.

UNLABELLED: Dynamic myocardial SPECT data acquired with 15-(123)I-(p-iodophenyl)-3-(R,S)-methylpentadecanoic acid (BMIPP) were analyzed by the Rutland method. The relative time-activity curves generated from dynamic SPECT in normal control subjects were compared with similar curves from patients with established ischemic heart disease (IHD) and doxorubicin-induced myocardial damage (DxMD). Comparison of such time-activity curves may provide some indirect information concerning qualitative differences in BMIPP metabolism. METHODS: Thirteen patients with various malignancies who received doxorubicin, 16 patients with IHD, and 15 normal control subjects were examined. Immediately after the bolus injection of BMIPP, dynamic data acquisition with a 3-head SPECT system was started and continued for 15 min. Using the time-activity curves of the myocardium as the output function (Mo(t)) and the time-activity curves of the left ventricular cavity as the input function (B(t)), the Rutland equation was calculated: Mo(t)/B(t) = F + K integral B(t)dt/B(t), where F is the blood - background subtraction factor and K is the uptake constant. The duration of the linear portion in this equation and the K values were evaluated. RESULTS: Mo(t)/B(t) was plotted against integral B(t)dt/B(t). Mo(t)/B(t) showed a good linear correlation with integral B(t)dt/B(t) from 30 s to 230 +/- 57 s in normal control subjects. The duration of this linearity was prolonged to 317 +/- 79 s in DxMD (P = 0.0014) and shortened to 182 +/- 58 s in IHD (P = 0.039). The mean K value was 0.0740 +/- 0.0184 in normal control subjects, significantly higher than the K values of 0.0599 +/- 0.0148 in DxMD patients (P = 0.026) and 0.0497 +/- 0.0189 (P = 0.0020) in IHD patients. CONCLUSION: Analysis of BMIPP dynamic SPECT data by the Rutland method is useful for detecting qualitative differences in BMIPP metabolism in various types of myocardial damage. It is speculated that the fatty acid metabolic disorder is characterized by a delay in metabolism in DxMD and by increased backdiffusion in IHD.