Masatoshi Minamisawa

Isolated left ventricular non-compaction cardiomyopathy in adults

Left ventricular non-compaction (LVNC) is a heart-muscle disorder characterized by prominent myocardial trabeculations and deep intertrabecular recesses in the LV cavity. LVNC is often diagnosed by echocardiography and cardiac magnetic resonance imaging, but a universally accepted definition of LVNC is lacking. Although the prevalence of LVNC in adults remains unclear, improvements in diagnostic techniques account for the relatively high incidence of LVNC in recent years. The clinical presentation is highly variable from asymptomatic to symptomatic. Meanwhile, the classical triad of heart failure, ventricular arrhythmias, and systemic embolism constitute typical complications of this disease. Unfortunately, there is no specific therapy for LVNC, and management depends on the clinical manifestations. In this review, we discuss what is currently known about LVNC and conclude that multicenter registries are required for a better understanding of this rare disorder.

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.

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.

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.

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.

Impact of combination therapy with statin and ezetimibe on secondary prevention for post-acute myocardial infarction patients in the statin era

Background Little is known concerning the effect of ezetimibe for secondary prevention in post-myocardial infarction (MI) patients. In this study, we investigated the secondary prevention effect of ezetimibe for post-MI patients. Methods This study is a retrospective analysis of Assessing Lipophilic vs. hydrophilic Statin therapy for Acute MI (ALPS-AMI study). The patients were divided into two groups: those administered a statin to control low density lipoprotein-cholesterol (LDL-C), the ezetimibe(−) group, and those administered ezetimibe in addition to a statin to control LDL-C, the ezetimibe(+) group. The endpoints were Major Adverse Cardiac and Cerebrovascular Event (MACCE), including all-cause death, recurrence of MI, stroke, and heart failure requiring hospitalization, and MACCE with revascularization. Results The ezetimibe(+) and ezetimibe(−) groups contained 113 and 337 patients, respectively. Incidences of MACCE and MACCE with revascularization were lower in the ezetimibe(+) group than in the ezetimibe(−) group (2.6% vs. 11.5%, p = 0.002; 23.0% vs. 36.7%, p = 0.014, respectively). Moreover, logistic regression analysis revealed ezetimibe(+) was a significant negative predictor of MACCE (OR 0.208, 95% CI 0.048 to 0.903, p = 0.047) and MACCE with revascularization (OR 0.463, 95% CI 0.258 to 0.831, p = 0.008). The preventive effect of ezetimibe against MACCE was observed in both moderate- and high-intensity lipid lowering treatment groups (0% vs. 17%; p = 0.077, 3.1% vs. 9.4%; p = 0.033). Conclusions In lipid-lowering therapy post-MI, ezetimibe and statin combination therapy improved MACCE with or without revascularization compared with statin monotherapy. These findings suggest that post-MI secondary prevention should be more intensive.

Predictive Value of Underweight Status for Patients With Peripheral Artery Disease With Claudication

We evaluated whether underweight status is associated with poor prognosis in patients with peripheral artery disease (PAD) with claudication, excluding critical limb ischemia. We identified 441 claudicants hospitalized for cardiovascular disease between 2005 and 2012. Patients were divided into 4 groups according to body mass index (BMI): an underweight group (BMI < 18.5 kg/m2; n = 48), a normal group (BMI = 18.5-25.0 kg/m2; n = 286), an overweight group (BMI = 25.0-30.0 kg/m2; n = 92), and an obese group (BMI ≥ 30.0 kg/m2; n = 15). The mean follow-up period was 3.5 ± 1.9 years. The underweight group had significantly lower levels of hemoglobin, albumin, estimated glomerular filtration rate, triglycerides, and hemoglobin A1c; higher levels of C-reactive protein and B-type natriuretic peptide; and a higher prevalence of hemodialysis. The incidence of all-cause death and cardiovascular death was significantly higher in the underweight group (underweight vs normal, 77.1% vs 33.0%; P < .001 and 43.3% vs 14.4%; P < .001, respectively). In a multivariate Cox analysis, underweight status was an independent predictor of all-cause death (hazard ratio, 2.53; 95% confidence interval, 1.58-4.18; P < .001). Therefore, promoting weight gain, as well as managing cardiovascular disease, may be important for underweight patients with PAD.