Soichiro Ebisawa

Assessment of lipophilic vs. hydrophilic statin therapy in acute myocardial infarction – ALPS-AMI study.

BACKGROUND Statins reduce the incidence of cardiovascular events, but no randomized trial has investigated the best statins for secondary prevention. We compared the efficacy of hydrophilic pravastatin with that of lipophilic atorvastatin in patients with acute myocardial infarction (AMI). METHODS AND RESULTS A prospective, multicenter study enrolled 508 patients (410 men; mean age, 66.0 ± 11.6 years) with AMI who were randomly assigned to atorvastatin (n=255) or pravastatin (n=253). The target control level of low-density lipoprotein cholesterol (LDL-C) was <100 mg/dl, and patients were followed for 2 years. The primary endpoint was the composite of death due to any cause, non-fatal myocardial infarction, non-fatal stroke, unstable angina or congestive heart failure requiring hospital admission, or any type of coronary revascularization. The primary endpoint occurred in 77 patients (30.4%) and in 80 patients (31.4%) in the pravastatin and atorvastatin groups, respectively (hazard ratio, 1.181; 95% confidence interval: 0.862-1.619; P=0.299), whereas greater reductions in serum total cholesterol and LDL-C were achieved in the atorvastatin group (P<0.001 for each). Changes in hemoglobin A1c, brain natriuretic peptide, and creatinine were not significant between the 2 regimens, and safety and treatment adherence were similar. CONCLUSIONS On 2-year comparison of hydrophilic and lipophilic statins there was no significant difference in prevention of secondary cardiovascular outcome.

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.

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

BACKGROUND The 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). METHODSANDRESULTS We 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). CONCLUSIONS Dysregulation 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

BACKGROUND Chronic 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). METHODS Screening 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. RESULTS Sixty 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). CONCLUSIONS An 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

BACKGROUND We 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. METHODS We 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. RESULTS The 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). CONCLUSIONS Regression of LVHT is associated with improvement in LV systolic function. LVRR might be associated with a favorable prognosis in patients with LVHT.

Impressive predictive value of ankle-brachial index for very long-term outcomes in patients with cardiovascular disease: IMPACT-ABI study

Background The ankle—brachial index (ABI) is a marker of generalized atherosclerosis and is predictive of future cardiovascular events. However, few studies have assessed its relation to long-term future cardiovascular events, especially in patients with borderline ABI. We therefore evaluated the relationship between long-term future cardiovascular events and ABI. Methods In the IMPACT-ABI study, a single-center, retrospective cohort study, we enrolled 3131 consecutive patients (67 ± 13 years; 82% male) hospitalized for cardiovascular disease and measured ABI between January 2005 and December 2012. After excluding patients with an ABI > 1.4, the remaining 3056 patients were categorized as having low ABI (≤ 0.9), borderline ABI (0.91–0.99), or normal ABI (1.00–1.40). The primary endpoint was MACE (cardiovascular death, myocardial infarction [MI] and stroke). The secondary endpoints were cardiovascular death, MI, stroke, admission due to heart failure, and major bleeding. Results During a 4.8-year mean follow-up period, the incidences of MACE (low vs. borderline vs. normal: 32.9% vs. 25.0% vs. 14.6%, P<0.0001) and cardiovascular death (26.2% vs. 18.7% vs. 8.9%, P<0.0001) differed significantly across ABIs. The incidences of stroke (9.1% vs. 8.6% vs. 4.8%, P<0.0001) and heart failure (25.7% vs. 20.8% vs. 8.9%, P<0.0001) were significantly higher in the low and borderline ABI groups than in the normal ABI group. But the incidences of MI and major bleeding were similar in the borderline and normal ABI groups. The hazard ratios for MACE adjusted for traditional atherosclerosis risk factors were significantly higher in patients with low and borderline ABI than those with normal ABI (HR, 1.93; 95%CI: 1.44–2.59, P < 0.0001, HR, 1.54; 95% CI: 1.03–2.29, P = 0.035). Conclusions The incidence of long-term adverse events was markedly higher among patients with low or borderline ABI than among those with normal ABI. This suggests that more attention should be paid to patients with borderline ABIs, especially with regard to cardiovascular death, stroke, and heart failure.

Long-Term Prognostic Implications of the Admission Shock Index in Patients With Acute Myocardial Infarction Who Received Percutaneous Coronary Intervention

The admission shock index (SI) enables prediction of short-term prognosis. This study investigated the prognostic implications of admission SI for predicting long-term prognoses for acute myocardial infarction (AMI). The participants were 680 patients with AMI who received percutaneous coronary intervention. Shock index is the ratio of heart rate and systolic blood pressure. Patients were classified as admission SI <0.66 (normal) and ≥0.66 (elevated; 75th percentile). The end point was 5-year major adverse cardiac events (MACEs). Elevated admission SI was seen in 176 patients. Peak creatine kinase levels were significantly higher and left ventricular ejection fraction was lower in the elevated SI group, which had a worse MACEs. In multivariate Cox regression analysis, SI ≥0.66 was a risk factor for MACE. Elevated admission SI was associated with poorer long-term prognosis.

Comparison of the standard and speckle tracking echocardiographic features of wild-type and mutated transthyretin cardiac amyloidoses

AIMS To compare cardiac function in patients with the two types of transthyretin (TTR)-related amyloidoses [wild-type (wt) and mutated (m) TTR amyloidoses (ATTR)] using standard and speckle tracking echocardiography (STE). METHODS AND RESULTS Twenty-one consecutive patients with biopsy-proved ATTRwt were compared with 21 patients with ATTRm from the database, matched by age and left ventricular (LV) wall thickness (n = 135, ATTRm). All patients were examined using 2D echocardiography. Apical four- and two-chamber, and long-axis views and basal, mid, and apical short-axis views were used to examine LV longitudinal, circumferential, and radial strains. LV ejection fraction (EF), LV basal circumferential/radial strain, and mid-radial strain were significantly lower in patients with ATTRwt compared with patients with ATTRm. There was no significant difference between the two groups in the other parameters. In the receiver-operating characteristic curve analysis, LVEF and LV basal mean radial strain were the best parameters for distinguishing between the two groups. CONCLUSION Patients with ATTRwt are characterized by lower LVEF, LV basal, and LV mid-radial strains compared with patients with ATTRm. LVEF and LV radial strain are useful in distinguishing between ATTRwt and ATTRm when TTR has been proved in biopsy specimens.

Prognostic Impact of Diastolic Wall Strain in Patients at Risk for Heart Failure

Diastolic wall strain (DWS) is based on the linear elastic theory, according to which decreased wall thinning during diastole reflects reduced left ventricular compliance and thus increased diastolic stiffness. Increased diastolic stiffness as assessed by DWS is associated with a worse prognosis in patients who have heart failure (HF) with preserved ejection fraction. However, there are no data about the prognostic value of DWS derived by M-mode echocardiography in patients at risk for HF. We retrospectively enrolled 1829 consecutive patients without prior HF who were hospitalized for cardiovascular (CV) diseases in our hospital between 2005 and 2012. Patients were divided into two groups stratified by DWS (median value 0.34). The study endpoint was the composite of major adverse cardiovascular events (MACE), including all-cause death, myocardial infarction, stroke, and hospitalization for HF. Over a 4.2-year median follow-up, adverse events were observed in 322 patients (17.6%). In Kaplan-Meier analysis, patients with low DWS (≤ 0.34, n = 915) showed worse prognoses than those with high DWS (> 0.34, n = 914) (MACE incidence 39.4% versus 31.9%, P = 0.011). In multivariate Cox proportional hazards analysis after the adjustment for age, sex, and echocardiographic parameters, low DWS (≤ 0.34) was significantly associated with the incidence of MACE (hazard ratio: 1.26, 95% confidence interval: 1.01-1.59; P = 0 .045). In patients without prior HF, DWS is an independent predictor of MACE. Simple assessment of DWS might improve risk stratification for CV events in those patients.

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.