Influence of Obstructive Sleep Apnea on Diastolic Heart Failure

Heart failure is frequently complicated by obstructive sleep apnea, which raises blood pressure and arrhythmiaand worsens prognosis. However, the incidence and influence of obstructive sleep apnea in patientswith diastolic heart failure is unknown. We hypothesized that patients with diastolic heart failurecomplicated by obstructive sleep apnea may have a worse outcome compared to those without obstructivesleep apnea. The study included 49 patients with an ejection fraction ≥ 50 %, of whom 34 had diastolic heartfailure and 15 did not have diastolic heart failure. The patients were examined in a sleep study and byechocardiography. Brain natriuretic peptide (BNP) levels were determined at admission and 1, 6 and 12months thereafter. The prevalence of obstructive sleep apnea in patients with diastolic heart failure( 18/34,53 %) was significantly higher than that in those without diastolic heart failure (3/15, 20 %)(p=0.032).BNP levels were high at admission in patients with diastolic heart failure, but then decreased gradually inthose without obstructive sleep apnea. However, BNP in patients with diastolic heart failure and obstructivesleep apnea remained high and was significantly elevated compared to the level in patients without obstructivesleep apnea at 6 and 12 months after admission. Patients with diastolic heart failure and obstructivesleep apnea showed prolongation of elevated BNP, indicating that complication of diastolic heart failure byobstructive sleep apnea may aggravate cardiac function

キュウセイ シンキンエン ガ ウタガワレ, ハツネツ ニヨリ ケンザイカ シタ ムショウコウセイ Brugadaショウコウグン ノ イチレイ

Brugada症候群は,重症不整脈を発症する症候群であるが,特異な心電図所見が明らかでなく診断に苦慮することがある.今回,発熱時心電図上ST上昇を認め,心筋炎を疑われ精査でBrugada症候群と診断した1例と,本邦で報告された発熱時顕在化した本症候群16例を検討した.症例は42歳男性,感冒症状とともに心電図所見でI.aV_R, aV_L, V_(1-4)のST上昇を認め急性心筋炎を疑われ入院した.心臓超音波検査でごく軽度心機能低下,心筋生検では異常なく,冠動脈造影では有意な狭窄はなかった.pilsicainide負荷でcoved型ST上昇を示し,電気生理学検査で容易に心室細動が誘発され,植込み型除細動器の植込み術が施行された.発熱時顕在化例で,高齢者群では高率に失神を発症した.Brugada症候群は発熱時顕在化することがあり,軽快により正常化するが,発熱と同時に失神や心室性不整脈が見られることがあり,十分な配慮が必要である.Brugada syndrome is a disease associated with severe arrhythmia but without specific ECG characteristics, which makes diagnosis difficult. We report the case of a patient with Brugada syndrome who had a ST segment elevation accompanied by fever, and we investigate 16 additional Japanese patients with Brugada syndrome that was recognized by fever. The patient was a 42-year-old man who showed ST segment elevation associated with cold symptoms and was admitted after diagnosis of myocarditis. Echocardiography exhibited slight cardiac dysfunction, but a myocardial biopsy showed no abnormalities and no significant stenosis was found in coronary angiography. After administration of pilsicainide, the patient showed covedtype ST segment elevation, and ventricular fibrillation was induced during an electrophysiological study ; therefore, an implantable cardioverter defibrillator (ICD) was installed. Among the patients with Brugada syndrome recognized by fever, many elderly patients showed syncope. In conclusion, Brugada syndrome frequently appears in fever and attention should be paid to elderly patients because they frequently develop fever and syncope simultaneously

マンセイ シンフゼン カンジャ ノ ジュウショウド ニヨル ヤカン ムコキュウ ト テイサンソ ケッショウ ノ ヒカク

慢性心不全(CHF)患者の重症度による夜間の酸素飽和度(SaO_2)と無呼吸の比較について検討を行うために安定した慢性軽症心不全患者6例(男4例,女2例63±5.2歳,左室駆出率:49.8±3.4%,NYHA class:IかII,mild-CHF群)と安定慢性重症心不全患者11例(男9例,女2例,62±11.9歳,左室駆出率:25.6±8.6%,NYHA class:III,severe-CHF群)患者を対象とし,両群を比較することにより検討を行った.全例において室内空気下にパルスオキシメーターを用いて24時間のSaO_2と脈拍数を連続記録した.そして夜間のSaO_2が3%あるいは4%以上低下した1時間あたりの回数(3%ODI,4%ODI),SaO_2の最低値を各々分析した.さらにポリソムノグラフィーを用いてSaO_2と睡眠に関する全てのデータを連続的に記録分析した.その結果,severe-CHF群のODIはmild-CHF群に比して有意に高値であった(4%ODI;5.8±5.1 vs 0.6±0.5,p<O.01.3%ODI;8.6±7.1 vs 1.0±O.9,p<0.01.).severe-CHF群のSaO_2の最低値はmild-CHF群に比して有意に低かった(82.2±7.1 vs 91.7±1.0%,p<0.01).severe-CHF群の夜間無呼吸は全例にみられ,大多数が中枢型であった(74.0±3.6%).以上より安定した重症心不全では夜間に低酸素血症と無呼吸がみられ,これらが臨床病像の悪化に影響していることが示唆される.Background : Patients with chronic heart failure (CHF) commonly experience Cheyne- Stokes respiration, central apnea, or obstructive apnea during sleep associated with oxygen desaturation. Nocturnal oxygen therapy and nasal continuous positive airway pressure (NCPAP) reduce sleep-disordered breathing in stable CHF. However, the relation between sleep apnea and nocturnal desaturation inpatients with severe, stable CHF in Japan is unknown. Objectives : To examine nocturnal oxygen saturation (SaO_2) and sleep apnea in Japanese patients with severe, stable CHF. Methods : The subjects were 11 patients with severe, stable CHF (9 men and 2 women, LVEF=25.6±8.6%, NYHA class=III, severe CHF group) and 6 with mild, stable CHF (4 men and 2 women, LVEF=49.8±3.4 %, NYHA class=I or II, mild CHF group). SaO_2 was continuously recorded with a pulse oximeter under room air, and 4 % and 3 % SaO_2 dip rate per hour (GDIs) and the SaO_2 nadir were analyzed. In addition, SaO_2 and sleep variables were continuously recorded with a polysomnograph. Results : ODI frequency in the severe CHF group was significantly higher than that in the mild CHF group (4% ODI, 5.8±5.1 vs 0.6±0.5 times/hour, respectively, p<0.01;3 % ODI, 8.6±7.1 vs 1.0±0.9 times/hour, respectively, p<0.01.). SaO_2 nadir in the severe CHF group was significantly lower than that in the mild CHF group (82.2±7.1 vs 91.7±1.0 %, p<0.01). All severe patients had sleep apnea, predominantly of the central type (74.0±3.6%). Conclusion : The frequency of nocturnal hypoxemia and apnea increases in patients with severe, stable CHF. Nocturnal hypoxemia and apnea may adversely effect the clinical status of these patients

Cardioprotective effects of low-dose combination therapy with a statin and an angiotensin receptor blocker in a rat myocardial infarction model

SummaryPurposeStatins attenuate angiotensin II-induced myocyte hypertrophy and this might increase the cardioprotective effects of renin–angiotensin system inhibition in the ischemic heart. In this study, we investigated the cardioprotective effects of combination therapy with low-dose simvastatin and low-dose losartan using a rat myocardial infarction model.MethodsMyocardial infarction was created in rats by left anterior descending artery ligation, and the animals were randomly allocated to one of four groups: control (n=8), losartan 3mg/kg/day (n=8), simvastatin 2mg/kg/day (n=8), and losartan 3mg/kg/day plus simvastatin 2mg/kg/day (n=8). Each treatment was started on the day of coronary ligation, and hemodynamics, myocardial blood flow, and infarct size were measured after 28 days.ResultsBlood pressure, heart rate, and left ventricular systolic and end-diastolic pressures were not significantly different comparing the control group with the 3 other treatment groups. The peak positive first derivative of left ventricular pressure (peak LV dP/dt) was equivalent comparing the control group with the losartan and simvastatin groups. However, the peak LV dP/dt was greater in the losartan plus simvastatin group than in the control group (p<0.05). Myocardial blood flow, left ventricular weight, and infarct size were not significantly altered by the 3 treatments.ConclusionsTreatment with 3mg/kg/day losartan plus 2mg/kg/day simvastatin but not losartan or simvastatin alone improved left ventricular systolic function in a rat myocardial infarction model. The result suggests that statins given in combination with angiotensin receptor blockers might have beneficial cardioprotective effects, even at low-doses for each agent

DataSheet_1_Integrated spatial analysis of gene mutation and gene expression for understanding tumor diversity in formalin-fixed paraffin-embedded lung adenocarcinoma.pdf

IntroductionA deeper understanding of intratumoral heterogeneity is essential for prognosis prediction or accurate treatment plan decisions in clinical practice. However, due to the cross-links and degradation of biomolecules within formalin-fixed paraffin-embedded (FFPE) specimens, it is challenging to analyze them. In this study, we aimed to optimize the simultaneous extraction of mRNA and DNA from microdissected FFPE tissues (φ = 100 µm) and apply the method to analyze tumor diversity in lung adenocarcinoma before and after erlotinib administration.MethodTwo magnetic beads were used for the simultaneous extraction of mRNA and DNA. The decross-linking conditions were evaluated for gene mutation and gene expression analyses of microdissected FFPE tissues. Lung lymph nodes before treatment and lung adenocarcinoma after erlotinib administration were collected from the same patient and were preserved as FFPE specimens for 4 years. Gene expression and gene mutations between histologically classified regions of lung adenocarcinoma (pre-treatment tumor in lung lymph node biopsies and post-treatment tumor, normal lung, tumor stroma, and remission stroma, in resected lung tissue) were compared in a microdissection-based approach.ResultsUsing the optimized simultaneous extraction of DNA and mRNA and whole-genome amplification, we detected approximately 4,000–10,000 expressed genes and the epidermal growth factor receptor (EGFR) driver gene mutations from microdissected FFPE tissues. We found the differences in the highly expressed cancer-associated genes and the positive rate of EGFR exon 19 deletions among the tumor before and after treatment and tumor stroma, even though they were collected from tumors of the same patient or close regions of the same specimen.ConclusionOur integrated spatial analysis method would be applied to various FFPE pathology specimens providing area-specific gene expression and gene mutation information.</p