Atsushi Izawa

Early administration of tolvaptan preserves renal function in elderly patients with acute decompensated heart failure

BACKGROUNDnLoop diuretics used in the treatment of heart failure often induce renal impairment. This study was conducted in order to evaluate the renal protective effect of adding tolvaptan (TLV), compared to increasing the furosemide (FRM) dose, for the treatment of acute decompensated heart failure (ADHF) in a real-world elderly patient population.nnnMETHODSnThis randomized controlled trial enrolled 52 consecutive hospitalized patients (age 83.4±9.6 years) with ADHF. The patients were assigned alternately to either the TLV group (TLV plus conventional treatment, n=26) or the FRM group (increasing the dose of FRM, n=26). TLV was administered within 24h from admission.nnnRESULTSnThe incidence of worsening renal function (WRF) within 7 days from admission was significantly lower in the TLV group (26.9% vs. 57.7%, p=0.025). Furthermore, the rates of occurrence of persistent and late-onset (≥5 days from admission) WRF were significantly lower in the TLV group. Persistent and late-onset WRF were significantly associated with a higher incidence of cardiac death or readmission for worsening heart failure in the 90 days following discharge, compared to transient and early-onset WRF, respectively.nnnCONCLUSIONSnEarly administration of TLV, compared to increased FRM dosage, reduces the incidence of WRF in real-world elderly ADHF patients. In addition, it reduces the occurrence of worse WRF-persistent and late-onset WRF-which are associated with increased rates of cardiac death or readmission for worsening heart failure in the 90 days after discharge.

Comparison of Inflammatory Biomarkers in Outpatients With Prior Myocardial Infarction

Inflammatory biomarkers have been proposed for use in the risk stratification of patients with acute myocardial infarction (AMI). We examined the value of inflammatory biomarkers over clinical features for predicting cardiovascular (CV) events in stable outpatients with MI. We enrolled 430 post-MI patients and measured their levels of high-sensitivity C reactive protein (hs-CRP), growth differentiation factor-15 (GDF-15), and the interleukin-1 receptor family member called ST2 (ST2), one month after AMI. Patients were prospectively followed for 3 years. In our study cohort (mean age, 66 ± 12 years; left ventricular ejection fraction, 55 ± 13%), CV events were observed in 39 patients (9.1%). Kaplan- Meier analysis revealed that patients with high levels of GDF-15 (≥ 1221.0 ng/L) showed poorer prognoses than those with low levels of GDF-15 (< 1221.0 ng/L) (20.4% versus 3.6%, P < 0.001); hs-CRP and ST2 did not show a similar correlation with prognoses. GDF-15 remained associated with CV events after adjusting for age, chronic kidney disease, and B-type natriuretic peptide (hazard ratio, 1.001; 95% confidence interval, 1.000 - 1.001; P = 0.046). GDF-15 provided an incremental predictive value for CV events over clinical features (incremental value in global χ(2) = 43.81, P < 0.001). In outpatients with prior MI, GDF-15 was an independent indicator of CV events, unlike hs-CRP and ST2. GDF15 provided an incremental prognostic value over clinical features.

Impact of oral beta-blocker therapy on mortality after primary percutaneous coronary intervention for Killip class 1 myocardial infarction

The use of beta-blockers therapy has been recommended to reduce mortality in patients with left ventricular dysfunction after acute myocardial infarction (AMI). Primary percutaneous coronary intervention (PCI), which has become the mainstay of treatment for AMI, is associated with a lower mortality than fibrinolysis. The benefits of beta-blockers after primary PCI in AMI patients without pump failure are unclear. We hypothesized that oral beta-blocker therapy after primary PCI might reduce the mortality in AMI patients without pump failure. The assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction (ALPS-AMI) study was a multi-center study that enrolled 508 AMI patients to compare the efficacy of hydrophilic and lipophilic statins in secondary prevention after myocardial infarction. We prospectively tracked cardiovascular events for 3xa0years in 444 ALPS-AMI patients (median age 66xa0years; 18.2xa0% women) who had Killip class 1 on admission and were discharged alive. The primary endpoint was all-cause mortality. The 3-year follow-up was completed in 413 patients (93.0xa0%). During this follow-up, 21 patients (4.7xa0%) died. In Kaplan–Meier analysis, patients on beta-blockers had a significantly lower incidence of all-cause mortality (2.7 vs. 7.3xa0%, log-rank pxa0=xa00.025). After adjusting for the calculated propensity score for using beta-blockers, their use remained an independent predictor of all-cause mortality (hazard ratio 0.309; 95xa0% confidence interval 0.116–0.824; pxa0=xa00.019). In the statin era, the use of beta-blocker therapy after primary PCI is associated with lower mortality in AMI patients with Killip class 1 on admission.

Prognostic Significance of Neuroadrenergic Dysfunction for Cardiovascular Events in Patients With Acute Myocardial Infarction

BACKGROUNDnThe dysregulation of systemic blood pressure (BP) variation or cardiac neuroadrenergic dysfunction is associated with adverse cardiovascular events. We aimed to clarify the prognostic significance of neuroadrenergic dysfunction for cardiovascular events in patients with acute myocardial infarction (AMI).nnnMETHODSANDRESULTSnWe enrolled 63 AMI patients (mean age, 67±12 years) underwent ambulatory BP monitoring (ABPM) and cardiac iodine-(123)metaiodobenzylguanidine (MIBG) imaging within 4 weeks after AMI onset. We analyzed the circadian BP pattern and heart-to-mediastinum (H/M) MIBG uptake ratio. All the patients were followed for 2 years. The study endpoint was a composite of major adverse cardiovascular events, including all-cause death, MI, coronary revascularization except for the MI culprit lesion, and stroke. Patients with a non-dipper pattern (n=29) or an H/M ratio <1.96 (n=28) had a worse prognosis than those with either a dipper pattern (n=34) or an H/M ratio ≥1.96 (n=35; log-rank, P=0.013 and 0.010, respectively). Patients with both a non-dipper pattern and an H/M ratio <1.96 (n=12) had a significantly worse prognosis than did the other patients (P=0.0020).nnnCONCLUSIONSnDysregulation of BP variation and cardiac MIBG uptake were associated with cardiovascular events following AMI. Examining ABPM with MIBG imaging may potentially improve risk stratification in these patients.

Association between estimated glomerular filtration rate and peripheral arterial disease

BACKGROUNDnChronic kidney disease (CKD) is an evolving paradigm for the risk assessment of cardiovascular diseases. We hypothesized that an advanced stage of CKD may predict the presence of peripheral arterial disease (PAD).nnnMETHODSnScreening for PAD by an ankle-brachial pressure index (ABI) ≤0.9 was conducted in a consecutive series of 583 subjects (mean age 68.1±12.9 years, 411 men). Levels of estimated glomerular filtration rate (eGFR) and factors associated with the presence of PAD were examined.nnnRESULTSnSixty patients (10.3%) had PAD and 192 patients (32.9%) had eGFR <60mL/min/1.73m(2) among all subjects. In patients with an advanced stage of CKD (stage ≥3, equivalent to eGFR <60mL/min/1.73m(2)), high prevalence of PAD (17.2%) and lower ABI levels (1.04±0.18) were observed. Univariate analyses revealed that PAD was associated with an advanced stage of CKD [odds ratio (OR) 1.850, 95% confidence interval (CI) 1.322-2.588, p<0.001], as well as age, male gender, systolic blood pressure, and hemoglobin A1c. Multivariate logistic regression analyses revealed that PAD was independently predicted by the CKD stages (OR 1.498, 95% CI 1.011-2.220, p=0.044, adjusted for covariates).nnnCONCLUSIONSnAn advanced stage of CKD is independently and significantly associated with the presence of PAD. Targeted screening with ABI measurement can be beneficial in patients with CKD.

Regression of left ventricular hypertrabeculation is associated with improvement in systolic function and favorable prognosis in adult patients with non-ischemic cardiomyopathy

BACKGROUNDnWe sometimes experience regression of left ventricular hypertrabeculation (LVHT), which is compatible with the diagnosis of LV non-compaction cardiomyopathy (LVNC) in adult patients. However, little is known about the association between LVHT regression and LV systolic function in adult patients.nnnMETHODSnWe prospectively examined 23 consecutive adult patients who fulfilled the echocardiographic criteria for LVNC. LV reverse remodeling (RR) was defined as an absolute increase in LV ejection fraction of >10% at 6 months follow-up. LVHT area was calculated by subtraction from the outer edge to the inner edge of the LVHT at end-systole.nnnRESULTSnThe mean follow-up period was 61 months. LVRR was observed in 9 patients (39%). The changes in the mean LVHT area showed significant correlation with the changes in LV ejection fraction (r=-0.78, p<0.0001). Cardiac death occurred in 7 patients (50%) without LVRR, but no patients with LVRR died (log-rank, p=0.003). Furthermore, composite of cardiac death and hospitalization for heart failure occurred in 10 patients (71%) without LVRR, whereas there was one patient with LVRR (log-rank, p<0.001).nnnCONCLUSIONSnRegression of LVHT is associated with improvement in LV systolic function. LVRR might be associated with a favorable prognosis in patients with LVHT.

Predictive Value of Combining the Ankle-Brachial Index and SYNTAX Score for the Prediction of Outcome After Percutaneous Coronary Intervention (from the SHINANO Registry)

The Synergy Between PCI With TAXUS and Cardiac Surgery (SYNTAX) score is effective in predicting clinical outcome after percutaneous coronary intervention (PCI). However, its prediction ability is low because it reflects only the coronary characterization. We assessed the predictive value of combining the ankle-brachial index (ABI) and SYNTAX score to predict clinical outcomes after PCI. The ABI-SYNTAX score was calculated for 1,197 patients recruited from the Shinshu Prospective Multi-center Analysis for Elderly Patients with Coronary Artery Disease Undergoing Percutaneous Coronary Intervention (SHINANO) registry, a prospective, observational, multicenter cohort study in Japan. The primary end points were major adverse cardiovascular and cerebrovascular events (MACE; all-cause death, myocardial infarction, and stroke) in the first year after PCI. The ABI-SYNTAX score was calculated by categorizing and summing up the ABI and SYNTAX scores. ABI ≤ 0.49 was defined as 4, 0.5 to 0.69 as 3, 0.7 to 0.89 as 2, 0.9 to 1.09 as 1, and 1.1 to 1.5 as 0; an SYNTAX score ≤ 22 was defined as 0, 23 to 32 as 1, and ≥ 33 as 2. Patients were divided into low (0), moderate (1 to 2), and high (3 to 6) groups. The MACE rate was significantly higher in the high ABI-SYNTAX score group than in the lower 2 groups (low: 4.6% vs moderate: 7.0% vs high: 13.9%, p = 0.002). Multivariate regression analysis found that ABI-SYNTAX score independently predicted MACE (hazards ratio 1.25, 95% confidence interval 1.02 to 1.52, p = 0.029). The respective C-statistic for the ABI-SYNTAX and SYNTAX score for 1-year MACE was 0.60 and 0.55, respectively. In conclusion, combining the ABI and SYNTAX scores improved the prediction of 1-year adverse ischemic events compared with the SYNTAX score alone.

Importance of cystatin C and uric acid levels in the association of cardiometabolic risk factors in Japanese junior high school students

BACKGROUNDnSerum cystatin C (CysC), a novel marker of renal function, is associated with the components of metabolic syndrome in adults. Little is known about the utility of CysC and its association with cardiometabolic risks in young subjects.nnnMETHODS AND RESULTSnIn a cohort of 454 Japanese junior high school students, the distribution of serum CysC levels and associated variables were analyzed. CysC levels were significantly higher in boys than in girls (0.92±0.10mg/L vs. 0.77±0.08mg/L, p<0.001). CysC was significantly correlated with serum creatinine (r=0.473, p<0.001), and serum uric acid (SUA) (r=0.546, p<0.001). Multivariable regression analysis revealed significant associations between CysC and SUA in all subjects (β=0.241, p<0.001), and in boys and girls separately (β=0.264 and 0.240, respectively, both p<0.001). Importantly, subjects with elevation of both serum CysC and SUA levels had the highest ratio of triglyceride to high-density lipoprotein cholesterol.nnnCONCLUSIONSnCysC had significant associations with both creatinine and SUA in Japanese junior high school students. The concomitant elevation of serum CysC and SUA levels was associated with subclinical lipid metabolism dysregulation, and suggested the presence of cardiometabolic risk accumulation.

Clinical Characteristics and Outcomes of Patients with High Ankle-Brachial Index from the IMPACT-ABI Study

Background Reduced ankle–brachial index (ABI) is a predictor of cardiovascular events. However, the significance of high ABI remains poorly understood. This study aimed to assess the characteristics and outcomes of patients with high ABI. Methods The IMPACT-ABI study was a retrospective cohort study that enrolled and examined ABI in 3,131 patients hospitalized for cardiovascular disease between January 2005 and December 2012. From this cohort, 2,419 patients were identified and stratified into two groups: high ABI (> 1.4; 2.6%) and normal ABI (1.0–1.4; 97.3%). The primary endpoint was the cumulative incidence of major adverse cardiovascular events (MACE), including cardiovascular-associated death, myocardial infarction, and stroke. Results Compared with the normal ABI group, patients in the high ABI group showed significantly lower body mass index (BMI) and hemoglobin level, but had higher incidence of chronic kidney disease and hemodialysis. Multivariate logistic regression analysis revealed that hemodialysis was the strongest predictor of high ABI (odds ratio, 6.18; 95% confidence interval (CI), 3.05–12.52; P < 0.001). During the follow-up (median, 4.7 years), 172 cases of MACE occurred. Cumulative MACE incidence in patients with high ABI was significantly increased compared to that in those with normal ABI (32.5% vs. 14.5%; P = 0.005). In traditional cardiovascular risk factors-adjusted multivariate Cox proportional hazard analysis, high ABI was an independent predictor of MACE (hazard ratio, 2.07; 95% CI, 1.02–4.20; P = 0.044). Conclusion Lower BMI, chronic kidney disease, and hemodialysis are more frequent in patients with high ABI. Hemodialysis is the strongest predictor of high ABI. High ABI is a parameter that independently predicts MACE.

Diagnostic advantage of stress computed tomography myocardial perfusion over single-photon emission computed tomography for the assessment of myocardial ischemia

BACKGROUNDnThis study compared adenosine stress computed tomography myocardial perfusion (CTP) with single-photon emission computed tomography (SPECT) in the diagnosis of functionally significant coronary artery stenosis using fractional flow reserve (FFR) as reference standard.nnnMETHODSnWe included a total of 93 coronary arteries from 31 patients in whom at least one vessel with ≥50% stenosis was detected with computed tomography coronary angiography. All patients underwent both SPECT and adenosine stress CTP, followed by invasive coronary angiography (ICA) and FFR. Diagnostic accuracy between CTP and SPECT was compared according to positive findings of either ≥99% stenosis on ICA or FFR ≤0.8.nnnRESULTSnAmong 78 vessels eligible for the quantitative analyses, significant coronary artery disease (CAD) was diagnosed in 22 vessels of 19 patients. Comparison of CTP vs. SPECT for sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in detecting significant CAD were 59% vs. 18%, 96% vs. 93%, 87% vs. 50%, 86% vs. 74%, and 86% vs. 72%, respectively.nnnCONCLUSIONSnCTP demonstrated a significant diagnostic advantage over SPECT in the identification of significant CAD, especially in terms of sensitivity and PPV. Adenosine stress CTP is useful for the noninvasive diagnosis of functionally significant CAD.