Ryo Munakata

Hyponatremia and In-Hospital Mortality in Patients Admitted for Heart Failure (from the ATTEND Registry)

Hyponatremia is known to be a poor prognostic factor in patients hospitalized with heart failure (HF), however not well studied in Japan. The aims of this study were to characterize hyponatremic hospitalized patients with HF and to clarify the relations between hyponatremia and detailed in-hospital outcomes in Japan. Among 4,837 hospitalized patients with HF enrolled in the Acute Decompensated Heart Failure Syndromes (ATTEND) registry, patient characteristics and in-hospital mortality in those with hyponatremia were examined. Hyponatremia (sodium <135 mEq/L) was observed in 11.6% of patients. Patients with hyponatremia were of similar age, included fewer men, and had a higher proportion of previous hospitalizations for HF compared to those with normonatremia. On admission, lower heart rates and blood pressures and higher brain natriuretic peptide levels were observed in patients with hyponatremia. During hospitalization, inotrope levels and mechanical device use were significantly higher in patients with hyponatremia. Rates of all-cause and cardiac death were significantly higher in patients with hyponatremia, 15.0% and 11.4%, respectively, compared to 5.3% and 3.6%, respectively, in those with normonatremia. In hyponatremic hospitalized patients with HF, cardiac death accounted for 76.2% of all-cause death. In conclusion, the present study demonstrates that in Japan hyponatremia in patients hospitalized with HF is relatively common and is associated with a very high in-hospital mortality.

Impact of Prediabetic Status on Coronary Atherosclerosis A multivessel angioscopic study

OBJECTIVE To determine if prediabetes is associated with atherosclerosis of coronary arteries, we evaluated the degree of coronary atherosclerosis in nondiabetic, prediabetic, and diabetic patients by using coronary angioscopy to identify plaque vulnerability based on yellow color intensity. RESEARCH DESIGN AND METHODS Sixty-seven patients with coronary artery disease (CAD) underwent angioscopic observation of multiple main-trunk coronary arteries. According to the American Diabetes Association guidelines, patients were divided into nondiabetic (n = 16), prediabetic (n = 28), and diabetic (n = 23) groups. Plaque color grade was defined as 1 (light yellow), 2 (yellow), or 3 (intense yellow) based on angioscopic findings. The number of yellow plaques (NYPs) per vessel and maximum yellow grade (MYG) were compared among the groups. RESULTS Mean NYP and MYG differed significantly between the groups (P = 0.01 and P = 0.047, respectively). These indexes were higher in prediabetic than in nondiabetic patients (P = 0.02 and P = 0.04, respectively), but similar in prediabetic and diabetic patients (P = 0.44 and P = 0.21, respectively). Diabetes and prediabetes were independent predictors of multiple yellow plaques (NYPs ≥2) in multivariate logistic regression analysis (odds ratio [OR] 10.8 [95% CI 2.09–55.6], P = 0.005; and OR 4.13 [95% CI 1.01–17.0], P = 0.049, respectively). CONCLUSIONS Coronary atherosclerosis and plaque vulnerability were more advanced in prediabetic than in nondiabetic patients and comparable between prediabetic and diabetic patients. Slight or mild disorders in glucose metabolism, such as prediabetes, could be a risk factor for CAD, as is diabetes itself.

Hypercytokinemia with 2009 pandemic H1N1 (pH1N1) influenza successfully treated with polymyxin B-immobilized fiber column hemoperfusion

In September 2009, a 16-year-old female with no medical history developed fever, general fatigue, and diarrhea. A rapid diagnosis kit at a local clinic showed type A influenza. She was given 10 mg zanamivir inhalation, twice daily. The following day, her body temperature rose to 41.7 C and she experienced respiratory distress. She was transported to our hospital by ambulance. On arrival, her blood pressure was 90/ 40 mmHg, heart rate 150/min, and respiratory rate 35/min. She was administered a large dose of crystalloid fluid and norepinephrine (0.3 lg/kg/min). Mechanical ventilation with endotracheal intubation was begun. Purulent sputum removed by suction contained Gram-positive cocci on a Gram-stained smear. Cultures of blood, urine, and stool testing for various pathogens were negative. Mechanical ventilation was performed in pressure control mode with PaO2/FiO2 (P/F) ratio of 148. Thereafter, a recruitment maneuver was performed, switching to airway pressure release ventilation (APRV) mode. P/F ratio temporarily improved to 224, but then deteriorated to 165. Oseltamivir (150 mg/day), sivelestat sodium hydrate (300 mg/day), and antibiotics (initially ampicillin/ sulbactam 6 g/day) were administered. On day 2, complicated by disseminated intravascular coagulation, no improvement in respiratory status was observed, prompting an increase in oseltamivir dosage to 300 mg/day. Type A influenza was confirmed as 2009 pandemic H1N1 (pH1N1) virus by polymerase chain reaction (PCR). On day 3, methicillin-resistant Staphylococcus aureus (MRSA) was identified in the sputum collected immediately after intubation. Antibiotics were changed to linezolid (12 g/day) plus clindamycin (1,800 mg/day) for MRSA. Serum cytokine levels were highly elevated (Fig. 1). We considered that the severe respiratory failure might be related to hypercytokinemia caused by pH1N1 and MRSA infection. With no improvement in oxygenation, polymyxin B-immobilized fiber column (PMX) hemoperfusion was begun in an attempt to reduce the inflammatory mediators and improve oxygenation. Oxygenation gradually improved; after 1 h, the P/F ratio increased from 144 to 184, and after 8 h to 308. PMX hemoperfusion was performed for 14 h; following cessation, oxygenation declined (P/F ratio 220). On days 4 and 5, PMX hemoperfusion was planned for 18 h on each day, and the P/F ratio increased to 407. Serum inflammatory mediators decreased to normal levels after the PMX treatments. She was extubated and discharged from the hospital. Respiratory failure accounts for a large proportion of pH1N1-related deaths. In influenza A (H5N1) virus infection, hypercytokinemia was observed in fatal cases [1]. We postulated that hypercytokinemia led to respiratory failure. A fatal case of

Admission time, variability in clinical characteristics, and in-hospital outcomes in acute heart failure syndromes: findings from the ATTEND registry.

acute heart failure syndromes: Findings from the ATTEND registry Yuichiro Minami ⁎, Katsuya Kajimoto , Naoki Sato , Dai Yumino , Masayuki Mizuno , Toshiyuki Aokage , Koji Murai , Ryo Munakata , Kuniya Asai , Yasushi Sakata , Takehiko Keida , Nobuhisa Hagiwara , Kyoichi Mizuno , Hiroshi Kasanuki , Teruo Takano d,1 a Department of Cardiology, Tokyo Womens Medical University, Tokyo, Japan b Department of Cardiology, Sensoji Hospital, Tokyo, Japan c Intensive and Cardiac Care Unit, Nippon Medical School, Tokyo, Japan d Department of Internal Medicine, Nippon Medical School, Tokyo, Japan e Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan f Department of Cardiology, Edogawa Hospital, Tokyo, Japan g Faculty of Science and Engineering, Waseda University, Tokyo, Japan

Oscillometric measurement of brachial artery cross-sectional area and its relationship with cardiovascular risk factors and arterial stiffness in a middle-aged male population

An enlarged arterial diameter is associated with an increased risk for cardiovascular disease. This study examined the relationship of noninvasively measured brachial artery cross-sectional area with cardiovascular risk factors and arterial stiffness in a middle-aged male population. Absolute volumetric changes of the brachial artery were measured with a newly developed oscillometric method during a general health examination in 387 men (mean age: 38±9 years) without known cardiovascular disease. Based on the measurement, the estimated area (eA) of the brachial artery at end-diastole was obtained. Brachial artery volume elastic modulus (VE) and brachial–ankle pulse wave velocity (baPWV) were simultaneously measured as indices of arterial stiffness by the same device. The relationships of eA with cardiovascular risk factors, including age, obesity, hypertension, dyslipidemia, impaired fasting glucose/diabetes mellitus (IFG/DM), hyperuricemia, smoking and their associated continuous variables, as well as VE and baPWV, were examined. Overall, the mean eA was 12.9±2.9 mm2. The eA was significantly higher in subjects with obesity, hypertension or IFG/DM than in those without each of these risk factors. In a multiple linear regression analysis, body mass index (β=0.31, P<0.001), age (β=0.25, P<0.001), systolic blood pressure (β=0.16, P=0.004) and pulse rate (β=−0.13, P=0.005) were independent determinants of eA. In contrast, neither VE nor baPWV were selected as independent determinants of eA. In conclusion, enlarged brachial artery cross-sectional area was significantly associated with cardiovascular risk factors such as age, body mass index and systolic blood pressure, but it was not associated with increased arterial stiffness.

Switching to Pitavastatin in Statin-Treated Low HDL-C Patients Further Improves the Lipid Profile and Attenuates Minute Myocardial Damage.

Background The aim of this study is to determine the prevalence of minute myocardial damage (MMD) in already statin-treated dyslipidemic patients with a low high-density lipoprotein-cholesterol (HDL-C) level, and to evaluate whether pitavastatin could affect the lipid profiles and biomarkers reflecting myocardial stress and injury. Methods Twenty patients (15 men; age 66 ± 8) being treated with any statin but who had HDL-C < 40 mg/dL, were switched to pitavastatin (2 mg/day) treatment. The patient lipid profiles and the levels of N-terminal pro-brain natriuretic peptide (NT-proBNP), high-sensitive troponin T (hsTnT), and high-sensitive C-reactive protein (hs-CRP) were evaluated for six months. Results At three months after the statin replacement, the HDL-C significantly increased from 37 ± 3 mg/dL to 40 ± 5 mg/dL (P < 0.05), and the low-density lipoprotein-cholesterol (LDL-C) and LDL-C/HDL-C ratio significantly reduced (100 ± 28 mg/dL to 86 ± 22 mg/dL, P < 0.05; 2.68 ± 0.67 to 2.17 ± 0.64, P < 0.05, respectively), and these changes were sustained for six months. In the whole study population, no significant changes were observed in the NT-proBNP, hsTnT, or hsCRP for six months. However, in 11 cases who showed a positive (> 0.003 ng/mL) hsTnT at baseline, a significant reduction in the hsTnT was observed (0.016 ± 0.020 ng/mL to 0.014 ± 0.020 ng/mL, P < 0.05), and its percent reduction significantly correlated with the percent increase in HDL-C (r = -0.68, P < 0.05). Conclusions MMD (positive hsTnT) was observed in more than half of patients with low HDL-C despite the administration of any statin, and the replacement of their previous statin with pitavastatin further improved their lipid profiles and led to better myocardial protection, possibly mediated via the elevation of the HDL-C level.

Clinical profile, management, and mortality in very-elderly patients hospitalized with acute decompensated heart failure: An analysis from the ATTEND registry.

BACKGROUND Acute decompensated heart failure (ADHF) is a leading cause of hospitalization among the elderly. Discussion of optimal management of ADHF in older patients is a growing health care priority. The aim of this study was to examine the clinical profile, management, and mortality in patients admitted with ADHF according to age. METHODS We analyzed 4824 patients enrolled in the Acute Decompensated Heart Failure Syndromes registry from April 2007 to December 2011. Patient characteristics, management, and in-hospital outcomes were compared among four age groups (<65, 65-74, 75-84, and ≥85 years). RESULTS The mean age of the overall population was 73 years; approximately 20% were aged ≥85 years. Older patients were more likely to be women and have preserved left ventricular ejection fraction (LVEF) and decreased renal function. Intravenous treatments were well administered in both young and elderly patients irrespective of LVEF. Invasive procedures were less frequently performed in the eldest group. The median length of hospital stay was 21 days, and in-hospital cardiac death in the eldest group was four-fold higher than that in the youngest group (2.2% vs. 8.9%, P<0.001). CONCLUSIONS Clinical characteristics of ADHF differ considerably with age, and cardiac death increases linearly with age. Despite a higher rate of preserved systolic function in very-elderly individuals aged ≥85 years, in-hospital mortality was higher, suggesting that more suitable treatments for the elderly might be needed.

Microvascular resistance in response to iodinated contrast media in normal and functionally impaired kidneys

Contrast‐induced nephropathy (CIN) is considered to result from intrarenal vasoconstriction, and occurs more frequently in impaired than in normal kidneys. It was hypothesized that iodinated contrast media would markedly change renal blood flow and vascular resistance in functionally impaired kidneys. Thirty‐six patients were enrolled (32 men; mean age, 75.3 ± 7.6 years) undergoing diagnostic coronary angiography and were divided into two groups based on the presence of chronic kidney disease (CKD), defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min per 1.73 m2 (CKD and non‐CKD groups, n = 18 in both). Average peak velocity (APV) and renal artery resistance index (RI) were measured by Doppler flow wire before and after administration of the iodinated contrast media. The APV and the RI were positively and inversely correlated with the eGFR at baseline, respectively (APV, R = 0.545, P = 0.001; RI, R = −0.627, P < 0.001). Mean RI was significantly higher (P = 0.015) and APV was significantly lower (P = 0.026) in the CKD than in the non‐CKD group. Both APV (P < 0.001) and RI (P = 0.002) were significantly changed following contrast media administration in the non‐CKD group, but not in the CKD group (APV, P = 0.258; RI, P = 0.707). Although renal arterial resistance was higher in patients with CKD, it was not affected by contrast media administration, suggesting that patients with CKD could have an attenuated response to contrast media.

Incidence and predictors of in-hospital non-cardiac death in patients with acute heart failure

Background: Patients with acute heart failure (AHF) commonly have multiple co-morbidities, and some of these patients die in the hospital from causes other than aggravated heart failure. However, limited information is available on the mode of death in patients with AHF. Therefore, the present study was performed to determine the incidence and predictors of in-hospital non-cardiac death in patients with AHF, using the Acute Decompensated Heart Failure Syndromes (ATTEND) registry Methods: The ATTEND registry included 4842 consecutive patients with AHF admitted between April 2007–September 2011. The primary endpoint of the present study was in-hospital non-cardiac death. A stepwise regression model was used to identify the predictors of in-hospital non-cardiac death. Results: The incidence of all-cause in-hospital mortality was 6.4% (n=312), and the incidence was 1.9% (n=93) and 4.5% (n=219) for non-cardiac and cardiac causes, respectively. Old age was associated with in-hospital non-cardiac death, with a 42% increase in the risk per decade (odds 1.42, p=0.004). Additionally, co-morbidities including chronic obstructive pulmonary disease (odds 1.98, p=0.034) and anaemia (odds 1.17 (per 1.0 g/dl decrease), p=0.006) were strongly associated with in-hospital non-cardiac death. Moreover, other predictors included low serum sodium levels (odds 1.05 (per 1.0 mEq/l decrease), p=0.045), high C-reactive protein levels (odds 1.07, p<0.001) and no statin use (odds 0.40, p=0.024). Conclusions: The incidence of in-hospital non-cardiac death was markedly high in patients with AHF, accounting for 30% of all in-hospital deaths in the ATTEND registry. Thus, the prevention and management of non-cardiac complications are vital to prevent acute-phase mortality in patients with AHF, especially those with predictors of in-hospital non-cardiac death.

Third heart sound in hospitalised patients with acute heart failure: insights from the ATTEND study.

Several previous studies have suggested that detection of a third heart sound (S3) in patients with chronic congestive heart failure is associated with adverse long‐term outcomes. However, the short‐term prognostic value of identifying an S3 on admission in patients with acute heart failure (AHF) is not well established. We therefore analysed the in‐hospital prognostic value of detecting an S3 on admission in hospitalised patients with AHF.