Kiyoshi Iida

Treatment of coronary spastic angina with a statin in addition to a calcium channel blocker: a pilot study.

Combined therapy with a statin and a calcium channel blocker, which can improve lipid metabolism and reduce oxidative stress, may attenuate coronary vasoconstriction in patients with coronary spastic angina (CSA). After 6 months of therapy with benidipine and pravastatin, an acetylcholine provocation test was performed a second time in 25 patients with CSA. The patients were divided into 2 groups according to whether the result of this second test was positive (n = 13) or negative (n = 12). The test was designated as positive when the intracoronary injection of acetylcholine induced angiographically demonstrable total or subtotal occlusion (positive-test group). In the negative-test group, significant decrease in the plasma levels of low-density lipoprotein (LDL) cholesterol (−20.7 ± 11.1%, P < 0.01 versus baseline) were observed along with a dramatic increase in the serum level of high-density lipoprotein (HDL) cholesterol (26.8 ± 13.2%, P < 0.01 versus baseline). Furthermore, a significant decrease of the malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, a marker of oxidative stress, was also observed (-22.6 ± 14.1%, P < 0.01 versus baseline) in this group. In the positive-test group, however, no significant changes were found in any of the aforementioned parameters. The results showed that improvement of lipid metabolism, especially an increase of HDL cholesterol level and a reduction of MDA-LDL, may inhibit vascular contractility.

Association of plasma level of malondialdehyde-modified low-density lipoprotein with coronary plaque morphology in patients with coronary spastic angina: implication of acute coronary events.

BACKGROUND Focal vasospasm is reportedly involved in a high incidence of acute coronary syndrome (ACS) as compared with diffuse vasospasm. No adequate studies have been conducted on the mechanism underlying the higher incidence of ACS involving focal vasospasm than of those involving diffuse vasospasm in patients with coronary spastic angina. METHODS AND RESULTS Blood samples were collected from the aortic root (Ao) and the coronary sinus (CS) before provoking left coronary vasospasm using intracoronary administration of acetylcholine. After relief of vasospasm, volumetric analyses of vasospastic lesions were evaluated with 3-dimensional intravascular ultrasound in 64 patients. The percent plaque volume was more prominent in focal (n=31) than in diffuse vasospasm (n=33) (40.9+/-9.4 vs. 23.3+/-9.2%, p<0.0001). The Cs-Ao difference of malondialdehyde-modified low-density lipoprotein (MDA-LDL) level, as a marker of atherothrombosis, in focal vasospasm increased significantly as compared with diffuse vasospasm (6.9+/-6.7 vs. 1.2+/-5.7 U/L, p=0.001). In a multiple-logistic regression analysis with the traditional risk factors, the Cs-Ao difference of MDA-LDL level was a variable differing independently between the 2 types of vasospasm. CONCLUSIONS Higher MDA-LDL levels were observed in the coronary circulation in patients with focal vasospasm than in those with diffuse vasospasm. Under these conditions, the dramatically increased percent plaque volume in cases with focal vasoconstriction may play an important role in the development of acute coronary events.

Relation of change in apolipoprotein B/apolipoprotein A-I ratio to coronary plaque regression after Pravastatin treatment in patients with coronary artery disease.

Some investigations have looked into the ability of measurements of apolipoprotein B/apolipoprotein A-I (apoB/apoA-I) ratio to predict cardiovascular events. We hypothesized that a decrease in the apoB/apoA-1 ratio by statin therapy would act on suppression of coronary plaque progression. A 6-month prospective study was conducted of 64 patients with coronary artery disease treated with pravastatin. The plaque volume, assessed by volumetric intravascular ultrasonography, had decreased significantly by 12.6% (p <0.0001 vs baseline). Although a significant decrease of 6.4% and 14.6% was found in the serum level of apoB and the apoB/apoA-1 ratio (p = 0.0001 and p <0.0001, respectively, vs baseline), a significant increase of 14.0% of and 12.0% in the level of apoA-I and apoA-II (both p <0.0001 vs baseline). No significant changes were found in the level of apoC-II or apoE. A stepwise regression analysis revealed that the change in the apoB/apoA-1 ratio was an independent predictor of the change in coronary plaque volume (beta coefficient 0.386; p = 0.0023). In conclusion, our results have indicated that the decrease in the apoB/apoA-I ratio is a simple predictor for coronary atherosclerotic regression: the lower the apoB/apoA-I ratio, the lower the risk of coronary atherosclerosis.

Cardiac resynchronization and cardioverter defibrillation therapy in a patient with isolated noncompaction of the ventricular myocardium.

Isolated noncompaction of the ventricular myocardium (INVM) is an unclassified cardiomyopathy and is thought to be due to arrest of myocardial morphogenesis. Left ventricular failure and ventricular arrhythmias may occur in approximately half of the patients and account for half of the death in this disorder. In this report, we describe a patient with INVM in whom cardiac resynchronization and cardioverter defibrillation therapy was effective for the improvement of left ventricular function and for the prevention of ventricular arrhythmias.

Time Interval from Symptom Onset to Hospital Care in Patients with Acute Heart Failure: A Report from the Tokyo Cardiac Care Unit Network Emergency Medical Service Database

Aims There seems to be two distinct patterns in the presentation of acute heart failure (AHF) patients; early- vs. gradual-onset. However, whether time-dependent relationship exists in outcomes of patients with AHF remains unclear. Methods The Tokyo Cardiac Care Unit Network Database prospectively collects information of emergency admissions via EMS service to acute cardiac care facilities from 67 participating hospitals in the Tokyo metropolitan area. Between 2009 and 2011, a total of 3811 AHF patients were registered. The documentation of symptom onset time was mandated by the on-site ambulance team. We divided the patients into two groups according to the median onset-to-hospitalization (OH) time for those patients (2h); early- (presenting ≤2h after symptom onset) vs. gradual-onset (late) group (>2h). The primary outcome was in-hospital mortality. Results The early OH group had more urgent presentation, as demonstrated by a higher systolic blood pressure (SBP), respiratory rate, and higher incidence of pulmonary congestion (48.6% vs. 41.6%; P<0.001); whereas medical comorbidities such as stroke (10.8% vs. 7.9%; P<0.001) and atrial fibrillation (30.0% vs. 26.0%; P<0.001) were more frequently seen in the late OH group. Overall, 242 (6.5%) patients died during hospitalization. Notably, a shorter OH time was associated with a better in-hospital mortality rate (odds ratio, 0.71; 95% confidence interval, 0.51−0.99; P = 0.043). Conclusions Early-onset patients had rather typical AHF presentations (e.g., higher SBP or pulmonary congestion) but had a better in-hospital outcome compared to gradual-onset patients.

Effect of Heart Failure Secondary to Ischemic Cardiomyopathy on Body Weight and Blood Pressure

Both the obesity paradox and blood pressure (BP) paradox remain ill defined. Because both obesity and hypertension are well-known predictors of coronary artery disease (CAD) and acute heart failure (HF), in the present study, we compared the obesity paradox and the BP paradox between patients with acute HF with and without a history of CAD. A multicenter retrospective study was conducted on 3,204 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; multivariate Cox regression analysis with backward stepwise selection was then used to identify significant factors. Kaplan-Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 27% of patients had a history of CAD, and the all-cause in-hospital mortality rate was 5%. In-hospital mortality was significantly lower for patients with obesity than in those without obesity (log-rank, p = 0.033). However, this obesity paradox disappeared in the group with HF and CAD (log-rank, p = 0.740). In contrast, in-hospital mortality was significantly lower for patients with high BP at admission, regardless of the presence of a history of CAD (log-rank, p <0.001 for both groups). In conclusion, a history of CAD canceled the obesity paradox in patients with acute HF, whereas the BP paradox persisted regardless of a history of CAD.

Association of plasminogen activator inhibitor-1 and low-density lipoprotein heterogeneity as a risk factor of atherosclerotic cardiovascular disease with triglyceride metabolic disorder: a pilot cross-sectional study

Background We hypothesized that an increase in plasminogen activator inhibitor 1 (PAI-1) might reduce low-density lipoprotein (LDL) particle size in conjunction with triglyceride (TG) metabolism disorder, resulting in an increased risk of atherosclerotic cardiovascular disease (ASCVD). Methods This study was carried out as a hospital-based cross-sectional study in 537 consecutive outpatients (mean age: 64 years; men: 71%) with one or more risk factors for ASCVD from April 2014 to October 2014 at the Cardiovascular Center of Nihon University Surugadai Hospital. The estimated LDL-particle size was measured as relative LDL migration using polyacrylamide gel electrophoresis with the LipoPhor system. The plasma PAI-1 level, including the tissue PA/PAI-1 complex and the active and latent forms of PAI-1, was determined using a latex photometric immunoassay method. Results A multivariate regression analysis after adjustments for ASCVD risk factors showed that an elevated PAI-1 level was an independent predictor of smaller-sized LDL-particle in both the overall patients population (&bgr;=0.209, P<0.0001) and a subset of patients with a serum low-density lipoprotein cholesterol (LDL-C) level lower than 100 mg/dl (&bgr;=0.276, P<0.0001). Furthermore, an increased BMI and TG-rich lipoprotein related markers [TG, remnant-like particle cholesterol, apolipoprotein (apo) B, apo C-II, and apo C-III] were found to be independent variables associated with an increased PAI-1 level in multivariate regression models. A statistical analysis of data from nondiabetic patients with well-controlled serum LDL-C levels yielded similar findings. Furthermore, in the 310 patients followed up for at least 6 months, a multiple-logistic regression analysis after adjustments for ASCVD risk factors identified the percent changes of the plasma PAI-1 level in the third tertile compared with those in the first tertile as being independently predictive of decreased LDL-particle size [odds ratio (95% confidence interval): 2.11 (1.12/3.40), P=0.02]. Conclusion The plasma PAI-1 levels may be determined by the degree of obesity and TG metabolic disorders. These factors were also shown to be correlated with a decreased LDL-particle size, increasing the risk of ASCVD, even in nondiabetic patients with well-controlled serum LDL-C levels.

Depiction of the discrepancy between fatty-acid metabolism and myocardial perfusion in takotsubo cardiomyopathy using dedicated cardiac semiconductor gamma camera.

Takotsubo cardiomyopathy is a syndrome with overt electrocardiographic changes, chest discomfort similar to acute coronary syndrome, typical apical ballooning and hyperkinesis in the basal left ventricle. Nuclear medicine technique demonstrates the discrepancies among reduced glucose utilization, reduced fatty-acid metabolism and normal myocardial perfusion in takotsubo cardiomyopathy. Positron emission computed tomography (PET) may prove reduced glucose utilization using F-fludeoxyglucose [1]. Single-photon emission computed tomography (SPECT) is used as a standard diagnostic modality to prove the discrepancy between reduced fatty-acid metabolism and normal perfusion in common clinical settings. A novel semiconductor gamma camera (D-SPECT, Spectrum Dynamics, Caesarea, Israel) has several technical features as follows, high spatial resolution, high energyspectrum resolution and high photon-count sensitivity [2]. It would be useful to prove the discrepancy between myocardial perfusion and fatty acid metabolism using both Tl and I-beta-methyliodophenyl pentadecanoic acid (BMIPP) in the diagnosis of reversible myocardial damage [3,4].

Takotsubo cardiomyopathy in two patients with microvascular angina

We present two cases in which takotsubo cardiomyopathy (TC) developed immediately after a diagnosis of microvascular angina had been established. One patient who had been diagnosed as having endothelium-dependent microvascular angina (microvascular spasm) developed TC three weeks after the initial admission. The other patient was diagnosed as having endothelium-independent microvascular angina (decreased coronary flow reserve) and subsequently developed TC after the discontinuation of nicorandil treatment. These cases may provide insight into the possible mechanisms underlying the pathophysiological findings of TC. <Learning objective: Impaired coronary microcirculation has been recently reported in many cases during the acute phase of takotsubo cardiomyopathy. However, the exact mechanism responsible for the coronary microvascular dysfunction associated with this entity remains unclear. This report highlights the importance of microvascular angina, which may play a role in the development of this cardiomyopathy.>.

Effects of glycemic control on in-hospital mortality among acute heart failure patients with reduced, mid-range, and preserved ejection fraction

The relationship between glycemic control and outcome in patients with heart failure (HF) remains contentious. A recent study showed that patients with HF with mid-range ejection fraction (HFmrEF) more frequently had comorbid diabetes relative to other patients. Herein, we examined the association between glycosylated hemoglobin (HbA1c) and in-hospital mortality in acute HF patients with reduced, mid-range, and preserved EF. A multicenter retrospective study was conducted on 5205 consecutive patients with acute HF. Potential risk factors for in-hospital mortality were selected by univariate analyses; then, multivariate Cox regression analysis with backward stepwise selection was performed to identify significant factors. Kaplan–Meier survival curves and log-rank testing were used to compare in-hospital mortality between groups. Across the study cohort, 44% (2288 patients) had reduced EF, 20% had mid-range EF, and 36% had preserved EF. The overall in-hospital mortality rate was 4.6%, with no significant differences among the HF patients with reduced, mid-range, and preserved EF groups. For patients with HFmrEF, higher HbA1c level was a significant risk factor for in-hospital mortality (hazard ratio 1.387; 95% confidence interval 1.014–1.899; P = 0.041). In contrast, HbA1c was not an independent risk factor for in-hospital mortality in HF patients with preserved or reduced EF. In conclusion, HbA1c is an independent risk factor for in-hospital mortality in acute HF patients with mid-range EF, but not in those with preserved or reduced EF. Elucidation of the pathophysiological mechanisms behind these findings could facilitate the development of more effective individualized therapies for acute HF.