Akihiko Matsumura

Tolvaptan reduces the risk of worsening renal function in patients with acute decompensated heart failure in high-risk population

BACKGROUND Although tolvaptan is a recently approved drug for heart failure and causes aquaresis without affecting renal function, its clinical efficacy for patients with acute decompensated heart failure (ADHF) is yet to be elucidated. METHODS AND RESULTS We conducted a prospective observational study in patients with ADHF and high risk for worsening renal function (WRF). Risk stratification for WRF was done by scoring system. Of 174 patients, 114 patients were included as high-risk population for WRF. Incidence of WRF, urine output within 24h and 48 h, and changes in brain natriuretic peptide (BNP) were recorded in 44 patients treated with tolvaptan plus conventional therapy, and 70 patients with only conventional therapy. Urine output at 24h and 48 h after admission were both significantly higher in the tolvaptan group (p=0.001 and <0.001, respectively), and changes in BNP were not significantly different (p=0.351). However, the incidence of WRF was significantly lower in the tolvaptan group compared to the conventional group (22.7% vs 41.4%, p=0.045). Logistic regression analysis showed that treatment with tolvaptan was an independent factor for reducing WRF (hazard ratio 0.28, 95% confidence interval; 0.10-0.84; p=0.023). CONCLUSION In patients with ADHF with high risk of WRF, treatment with tolvaptan could prevent WRF compared to conventional therapy.

Pregnancy in Takayasu arteritis from the view of internal medicine

SummaryTo evaluate the influence of pregnancy on the morbid condition of Takayasu arteritis, we summarized the clinical data and pregnant courses of 18 patients with Takayasu arteritis and a total of 22 deliveries. We followed C-reactive protein (CRP) scores in 16 of 18 patients (20 of 22 deliveries) to ascertain the inflammatory condition inherent in Takayasu arteritis 1 year prior to, during, and 1 year after pregnancy. We also evaluated digital plethysmograms (pulse amplitude, pulse wave, crest time) to follow the hemodynamical condition of patients before, during, and after pregnancy. CRP scores improved significantly during pregnancy and 1 year after delivery. In the digital plethysmograms, pulse amplitude and wave also exhibited improvement after delivery, but crest time remained unchanged. This indicated that pregnancy is a state favorable to this disease. Some factors, such as the sex hormone progesterone, may induce this condition, but the details are still unknown. In conclusion, inflammatory activity and the hemodynamic state improve with pregnancy in patients with Takayasu arteritis. The physiologic aspects which cause this improvement should be maintained even after pregnancy.

Endothelial dysfunction measured by peripheral arterial tonometry predicts prognosis in patients with heart failure with preserved ejection fraction

BACKGROUND There is need for risk stratification of adverse events in patients with heart failure with HFpEF as the number of patients is increasing and prognosis of this population is poor. This study was performed to determine whether endothelial dysfunction measured by peripheral artery tonometry (PAT) can predict prognosis of patients with heart failure with preserved ejection fraction (HFpEF). METHODS We included 159 patients with HFpEF, and log-transformed reactive hyperemia index (L_RHI) was measured. Patients were followed-up for HF-related events, which including HF-related death and re-hospitalization due to congestive heart failure for 300 days. RESULTS A total of 32 HF-related events occurred during follow-up, including 4 deaths due to HF and 28 cases of re-hospitalization due to acute decompensated HF. Cox regression analysis indicated that L_RHI (HR 0.56, 95% CI: 0.39-0.80 for an increase of 0.1) was an independent predictor of HF-related events. Receiver operating characteristic analysis was performed for L_RHI, and the area under the curve was 0.73 (95% CI: 0.62-0.83). Moreover, a value of 0.49 was suggested as the optimal cut-off value for prediction of adverse events in this population. CONCLUSION L_RHI measured by non-invasive PAT is a predictor of poor prognosis in patients with HFpEF.

Prognostic implications of chronic kidney disease and anemia after percutaneous coronary intervention in acute myocardial infarction patients

Anemia is a common complication of chronic kidney disease (CKD), and a few studies suggest that both CKD and anemia have a marked impact on the prognosis of patients with cardiovascular disease. We retrospectively analyzed the prevalence of CKD and anemia in 312 patients with acute myocardial infarction (AMI). The patients were divided into four groups according to the presence of CKD and anemia. Chronic kidney disease was defined as estimated glomerular filtration rate <60 ml/min/1.73 m2, and anemia was defined according to the World Health Organization definition. Of 312 AMI patients, 166 (53.2%) had CKD and 87 (27.8%) had anemia. A powerful relationship was observed between both CKD and anemia and major adverse cardiac and cerebrovascular events (MACCE) or death by any cause. After adjustment for comorbidities, the hazard ratio (HR) for MACCE was significantly higher in the anemia-only group (HR 5.42, 95% confidence interval (CI) 1.38–21.27, P = 0.015), the CKD-only group (HR 6.4, 95% CI 2.09–19.58, P = 0.001), and the CKD and anemia group (HR 11.61, 95% CI 3.65–36.89, P < 0.001). With respect to death by any cause, the HR was significantly higher in the CKD-only group (HR 2.68, 95% CI 1.02–7.02, P = 0.045) and the CKD and anemia group (HR 4.40, 95% CI 1.56–12.43, P = 0.005). One-half of the patients with AMI had CKD as well. Furthermore, when anemia coexisted with CKD, these conditions had a multiplicative amplification effect on the risk of MACCE and death by any cause in patients with AMI.

Carperitide Is Associated With Increased In-Hospital Mortality in Acute Heart Failure: A Propensity Score-Matched Analysis.

BACKGROUND Carperitide (α-human A-type natriuretic peptide) has been used for more than one-half of all acute heart failure (AHF) patients in Japan. However, its clinical effectiveness is not well documented. METHODS We retrospectively identified AHF patients presenting with acute onset or worsening of symptoms and admitted to 1 of the 3 participating hospitals. Propensity score-matched analysis was performed. The primary end point was in-hospital mortality. RESULTS Of all of the AHF patients included in this study, 402 (38.7%) were treated with carperitide, and in-hospital mortality rate for the total cohort was 7.6%. We matched 367 pairs of patients treated with and without carperitide according to propensity score. In this matched cohort, treatment with carperitide was associated with in-hospital mortality (odds ratio [OR] 2.13, 95% confidence interval [CI] 1.17-3.85; P = .013). Potentially more harmful effects were observed in elderly patients (OR 2.93, 95% CI 1.54-5.91). CONCLUSIONS Carperitide was significantly associated with increased in-hospital mortality rate in AHF patients. Our results strongly suggest the necessity for well designed randomized clinical trials of carperitide to determine its clinical safety and effectiveness.

Beta-blocker prevents sudden cardiac death in patients with hemodialysis

BACKGROUND Beta blockers were shown to prevent SCD in cardiomyopathy or coronary artery disease patients. Dialysis patients show elevated mortality rates, predominantly due to cardiovascular disease. SCD is now one of the leading causes of death in this population. However, the prevention of SCD remains to be elucidated. METHODS We conducted a retrospective study of 316 patients from a database of all patients undergoing maintenance hemodialysis and followed up for 4.9 years. All patients were followed-up until death. Cox regression analysis was used to adjust the hazard ratio for beta blocker use with time until death. RESULTS SCD occurred during the study period in 3 (3.8%) patients in the beta blocker group and in 27 (11.4%) patients in the non-beta blocker group (P=0.047). Death from all causes occurred in 15 (18.8%) patients in the beta blocker group and in 97 (41.3%) patients in the non-beta blocker group (P<0.001). Kaplan-Meier curve showed that the rates of both SCD and all-cause death were lower in the beta blocker group (log-rank test, P=0.028 and P<0.001, respectively). In the Cox regression model, beta blocker use was significantly associated with lower adjusted risk of SCD (multivariate adjusted hazard ratio, 0.201; 95% confidence interval, 0.058-0.693; P=0.011). CONCLUSION In hemodialysis patients, beta blocker use was associated with lower risks of SCD and death from all causes. Thus, beta blocker use in this high-risk population may substantially improve outcome.

Plaque morphologies and the clinical prognosis of acute coronary syndrome caused by lesions with intact fibrous cap diagnosed by optical coherence tomography

BACKGROUND Pathological studies have suggested that acute coronary syndrome (ACS) may be caused by culprit lesions with intact fibrous cap (IFC), including plaque erosions. This study sought to evaluate the morphological features and clinical outcomes of patients with ACS caused by lesions with IFC. METHODS A total of 318 patients with ACS who underwent optical coherence tomography (OCT) of a culprit lesion were investigated. The culprit lesions were categorized as follows: those with plaque rupture (PR group), those with an IFC (IFC group), and those with a massive thrombus precluding plaque visualization (MT group). Intravascular ultrasound (IVUS) was performed in 297 patients. Clinical follow-up data were collected regarding adverse cardiac events, including death, myocardial infarction, revascularization, and congestive heart failure requiring hospitalization. RESULTS Culprit lesions were categorized into 141 RPs, 131 IFCs, and 46 MTs. IFC group exhibited a smaller remodeling index and less frequently attenuated plaques on IVUS. Three hundred and seven patients (96.5%) were followed for a median follow-up duration of 576 days. Adverse cardiac events were observed in 93 patients (30.3%). Kaplan-Meier analysis demonstrated a significantly lower event rate in IFC group compared with the RP and MT groups. Cox proportional hazard analysis demonstrated that an IFC and multivessel disease were independent predictors of adverse events [hazard ratio 0.57, 95% confidence interval (CI) 0.33-0.98, p=0.043 and hazard ratio 1.72, 95% CI 1.09-2.73, p=0.021]. CONCLUSIONS Culprit lesions with IFC showed smaller remodeling indices by IVUS, and were associated with better long-term prognosis compared with those with plaque rupture.

A case of giant cell arteritis with massive pericardial effusion

Giant cell arteritis (GCA) is a chronic inflammatory disease of the medium and large blood vessels. The early symptoms of this disease are nonspecific, and pericardial effusion is a rare manifestation of GCA. Recently, we investigated a case of GCA in which massive pericardial effusion was the initial symptom, and active aortitis was observed on positron emission tomography with fluorine-18 fluorodeoxyglucose. These observations indicated that pericardial effusion could occur in patients with GCA.

Improvement of HAS-BLED bleeding score predictive capability by changing the definition of renal dysfunction in Japanese atrial fibrillation patients on anticoagulation therapy

BACKGROUND AND PURPOSE Severe chronic kidney disease (CKD) is a risk factor for hemorrhagic events in atrial fibrillation (AF) patients on anticoagulation therapy. We postulated that even moderate CKD may be a risk factor for hemorrhage and this recognition would improve predictive capabilities of hemorrhagic risk stratification models in Japanese patients. METHODS AND SUBJECTS In this prospective study, 231 non-valvular AF patients were divided into three groups according to estimated glomerular filtration rate (eGFR) and followed-up for a median of 7.1 years. The clinical endpoint was a major hemorrhagic event (MHE). HAS-BLED score was calculated for the cohort and the predictive capability of the original HAS-BLED score was compared with that in which renal dysfunction was redefined as eGFR<60mL/min/1.73m(2). RESULTS Forty-four MHEs occurred during follow-up. Compared to no/mild CKD group (≥60mL/min/1.73m(2)), both moderate (30-59mL/min/1.73m(2)) and severe (<30mL/min/1.73m(2)) CKD groups had higher MHE risks (log rank: both p<0.001). MHE risk of patients with moderate CKD was more than threefold higher than the no/mild CKD group even after adjusting for other risk factors (hazard ratio 3.8, 95% confidence interval 1.7-8.7). The C-statistic in receiver-operating curve analysis was numerically but not significantly superior in modified HAS-BLED score compared to original HAS-BLED score (0.67 and 0.64, respectively; p=0.55). However, using modified HAS-BLED score was associated with significant improvement of net reclassification improvement (0.50, p=0.002) and integrated discrimination improvement (0.033, p=0.043). CONCLUSIONS Moderate CKD contributes to the risk of future major hemorrhagic events in AF patients. Modification of HAS-BLED score by changing the definition of renal failure markedly improved predictive capability.

Recovery from hyponatremia in acute phase is associated with better in-hospital mortality rate in acute heart failure syndrome

BACKGROUND Although hyponatremia on admission is a predictor of poor prognosis in acute heart failure (AHF) patients, little is known about the association between changes in sodium level in acute phase and in-hospital mortality. This study was performed to clarify the impact of sodium level improvement in the early phase on prognosis in AHF patients. METHODS A total of 882 consecutive hospitalized AHF patients were retrospectively enrolled in this study. Sodium levels were evaluated on days 1 and 3 of admission, and patients were classified into three groups: patients with hyponatremia on admission and day 3 (hypo-hypo group); patients with hyponatremia on admission and normonatremia on day 3 (hypo-normo group); and patients with normonatremia on admission (normo group). RESULTS Hyponatremia (sodium ≤135 mEq/L) was observed in 14.3% of cases. In multivariate linear regression analysis, age (standardized beta=0.084), male gender (standardized beta=-0.072), history of ischemic heart disease (standardized beta=-0.069), baseline sodium level (standardized beta=-0.435), and tolvaptan use (standardized beta=0.093) were independent determinants of changes in sodium level from day 1 to day 3. In-hospital mortality rates were significantly higher in the hypo-hypo group (23.7%) and hypo-normo group (9.7%) than the normo group (6.9%) (p<0.001). After adjustment for covariates, both hypo-normo (OR: 0.28, 95% CI: 0.08-0.93, p=0.038) and normo (OR: 0.42, 95% CI: 0.20-0.88, p=0.022) groups showed significantly lower in-hospital mortality rates than the hypo-hypo group. CONCLUSION Early recovery from hyponatremia in AHF patients is associated with lower in-hospital mortality rate.