Decreased coronary blood flow velocity in two patients with coronary microvascular spasm: case series†.

INTRODUCTION: Diagnostic criteria for coronary microvascular spasm (CMS) have not yet been fully established. CASE PRESENTATION: We present two cases of CMS in which decreased coronary blood flow velocities were observed during acetylcholine (ACH) provocation tests. The first patient suffered from chest pain occurring while at rest. The patient underwent coronary angiography (CAG), which revealed a decrease in the average peak velocity (APV) from 29 cm/s to 14 cm/s and a slow flow phenomenon following ACH injection. The second patient suffered from chest pain occurring during the night. The patient underwent CAG, which revealed a decrease in the APV from 17 cm/s to 7 cm/s with no significant epicardial coronary artery spasm following ACH injection. Both patients complained of chest pain, and electrocardiogram changes were observed in leads equivalent to the distal area of the vessel during an ACH provocation test. These findings were consistent with CMS, and their conditions improved under medical treatment. DISCUSSION: A transient decrease in coronary blood flow velocity following ACH administration might be a phenomenon specific to CMS. These cases may provide some insight into the underlying pathophysiology of CMS.

Complete occlusion of the left main trunk coronary artery by a cardiac papillary fibroelastoma in a hemodynamically unstable patient.

Papillary fibroelastomas are benign cardiac tumors with high embolic potential. The majority of cases of complete obstruction of the left main trunk (LMT) of the coronary artery are diagnosed via autopsy following sudden death; survival is rare in this setting. We present the case of a 60-year-old woman who underwent stent placement in the LMT three years prior to developing chest pain and cold sweats. On coronary arteriography, the catheter could not be advanced into the LMT due to resistance in the ostium. Insertion of the catheter was achieved after the resolution of resistance via catheterization of the LMT by means of an intra-aortic balloon pump drive system. The LMT was normal, and the patient's circulatory failure improved. The cause of the LMT embolism was a cardiac papillary fibroelastoma. Primary surgical excision is the recommended therapy for symptomatic cardiac papillary fibroelastoma. If the patient is hemodynamically stable, it may be possible to delay surgery. However, the patient in question developed cardiogenic shock secondary to two-vessel obstruction by the tumor. Therefore, even if the tumor had been removed using an intra-aortic balloon pump, the patient may not have survived until surgery. .

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. .

Development of a model for prediction of coronary atherosclerotic regression: evaluation of high-density lipoprotein cholesterol level and peripheral blood monocyte count.

Monocytes and high-density lipoprotein cholesterol (HDL-C) play important roles in the process of coronary atherosclerosis. We hypothesized that a reasonable predictive model of coronary plaque regression might be constructed using the change in the peripheral monocyte count and the serum HDL-C level. The plaque volume, as assessed by volumetric intravascular ultrasound, was measured at the baseline and after 6 months of pravastatin therapy in 114 patients with coronary artery disease. After 6 months of pravastatin therapy, a significant decrease of the plaque volume by 9.9% (p < 0.0001, vs. baseline) was observed; furthermore, a corresponding increase of the serum HDL-C level and decrease of the peripheral blood monocyte count were also seen (12.5%, p < 0.01 and -7.3%, p < 0.0001). In a multivariate regression analysis using the serum lipids and traditional risk factors as the covariates, the increase in the serum HDL-C (ß -0.56, p < 0.0001) and the decrease in monocyte count (ß 0.23, p = 0.03) were identified as independent predictors of the plaque regression. A model for the prediction of plaque regression according to whether the achieved the change in (Δ) monocyte count and ΔHDL-C were above or below the median values was prepared. Among the four groups, the group with ΔHDL-C ≥8.8% and Δmonocyte count ≤-8.6% showed the largest plaque regression (-20.4%), and the group with ΔHDL-C <8.8% and Δmonocyte count >-8.6% showed the increase of the plaque volume (2.6%). In view of the inflammatory nature of atherosclerosis, the model constructed using the two predictors may be a useful model for the prediction of plaque regression.

Low-density lipoprotein cholesterol/apolipoprotein B ratio may be a useful index that differs in statin-treated patients with and without coronary artery disease: a case control study.

Low density lipoproteins (LDLs) are heterogeneous aggregations of molecules of different particle sizes, and small-size LDLs are more potent risk factors for atherosclerosis. We examined the qualitative characteristics of LDLs in patients with stable coronary artery disease (CAD) receiving statin therapy. LDL-particle size was estimated based on the LDL-cholesterol/apolipoprotein B ratio (LDL-C/apoB) in 214 age-adjusted men receiving statin therapy. The LDL-C/apoB ratio was significantly lower in the CAD (+) group (n = 107) than in the CAD (-) group (n = 107) (median, 1.17 versus 1.19, P = 0.0095). LDL-C/apoB was significantly lower in patients with serum TG ≥ 150 mg/dL than in those with serum TG < 150 mg/dL, and in patients with serum HDL-C < 40 mg/dL than in those with serum HDL-C ≥ 40 mg/dL (1.06 versus 1.18, P = 0.012; 1.08 versus 1.22, P = 0.0023). Stepwise logistic regression analysis revealed that elevated serum TG was an independent predictor for smaller sizes of LDLs, both in the overall subjects (ß : -0.165, P = 0.02) as well as in the subset with serum LDL-C < 100 mg/dL (ß : -0.252, P = 0.011). This study demonstrated that not only the absolute serum LDL-C level, but also the qualitative characteristics of LDL may be monitored for secondary prevention of CAD. Such monitoring is particularly important in patients with elevated serum TG levels, which is associated with smaller sizes of LDL-particles.

Coronary plaque regression and lifestyle modification in patients treated with pravastatin. - Assessment mainly by daily aerobic exercise and an increase in the serum level of high-density lipoprotein cholesterol -.

BACKGROUND: The purpose of this study was to explore the effect of lifestyle modification, mainly daily aerobic exercise, on coronary atherosclerosis in patients with coronary artery disease (CAD). METHODS AND RESULTS: A 6-month prospective observational study was conducted with 84 CAD patients receiving pravastatin treatment in order to evaluate the relationship between lifestyle modification, in particular aerobic exercise, and plaque volume as assessed by intravascular ultrasound (IVUS). Lifestyle during the study period was assessed by the-lifestyle modification score. A significant decrease in plaque volume by 12.9% was observed after 6 months of pravastatin therapy (P<0.0001 vs baseline). The change in plaque volume correlated with the change in the serum level of high-density lipoprotein cholesterol (HDL-C) (r=-0.549, P<0.0001), non-HDL-C (r=0.248, P=0.03), low-density lipoprotein cholesterol/HDL-C (r=0.505, P<0.0001), apolipoprotein (apo) A-1 (r=-0.335, P=0.007) and apoB/apoA-1 (r=0.335, P=0.007), and lifestyle modification score (r=-0.616, P<0.0001). There was a clear positive correlation between a change in the serum HDL-C level and lifestyle modification score. Multivariate regression analysis revealed that the increase in serum HDL-C level and lifestyle modification score were independent predictors of coronary plaque regression. CONCLUSIONS: An appropriate combination of statin therapy and lifestyle modification, in particular, physical activity, may result in coronary plaque regression. This combined treatment strategy, inducing an increase of the serum HDL-C, may contribute to coronary plaque regression.

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.

Association of leukocyte subtype counts with coronary atherosclerotic regression following pravastatin treatment.

The purpose of this study was to clarify the relation between differential leukocyte counts and inhibition of the development of coronary atherosclerosis in patients with coronary artery disease. A 6-month prospective study was conducted in 84 patients treated with pravastatin. Plaque volume, as assessed by volumetric analysis using intravascular ultrasound, decreased significantly by 12.6% (p <0.0001 vs baseline) after treatment; furthermore, a corresponding decrease of total leukocyte count (8.9%, p <0.01 vs baseline) was seen. Change in plaque volume was correlated with changes in monocyte (r = 0.35, p = 0.002) and lymphocyte (r = 0.25, p = 0.03) counts but not with changes in neutrophil, eosinophil, or basophil counts. In a multivariate regression analysis with changes in serum lipids, traditional risk factors, and medications as covariates, the decrease in monocyte count was identified as an independent predictor of coronary plaque regression (beta coefficient 0.313, 95% confidence interval 0.089 to 0.353, p = 0.0014). No correlation was found between change in monocyte count and changes in any other lipid levels. This study demonstrated that monocyte count was the only leukocyte type significantly and independently associated with coronary atherosclerotic regression, even after adjustment for changes in any lipid levels. In conclusion, the decrease in monocyte count as a nonlipid-lowering effect of statins may be used as a novel marker of coronary atherosclerotic regression.

Effects of enalapril and losartan in left ventricular remodeling after acute myocardial infarction: a possible mechanism of prevention of cardiac events by angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in high-risk myocardial infarction.

BACKGROUND: Angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin II receptor blockers (ARB) have been shown to have a significant cardioprotective effect in high-risk patients after myocardial infarction (MI). However, there are few data on the effects of these drugs on left-ventricular (LV) remodeling after MI in Japanese patients. METHODS AND RESULTS: We randomly assigned 100 patients with anterior-wall MI who had received reperfusion therapy to treatment with either enalapril (n=50) or losartan (n=50), and calculated the LV ejection fraction (LVEF) and LV end-diastolic volume index (LVEDVI) in these patients at baseline and after 6 months of treatment. While a significant increase in the LVEF as compared with that at the baseline was observed in both groups, no significant difference was found in the rate of change of this parameter between the two groups. However, inverse correlations were observed between the baseline LVEF and LVEDVI and also the rates of change of the two parameters, suggesting that the greater the compromise of the LV function at baseline, the greater the preventive effect of both classes of drugs on LV remodeling. CONCLUSION: The results of this study suggest that neither enalapril nor losartan is superior to the other in terms of the effect on LV remodeling after MI in Japanese patients. In addition, the suppressive effect of both classes of drugs on LV remodeling was greater in patients with more extensive infarction and greater compromise of LV function at baseline.

Association of body mass index with coronary plaque regression: 6-month prospective study.

AIM: Obesity is a well known strong risk factor for coronary artery disease (CAD). We prospectively investigated the influence of body mass index (BMI) on the inhibitory effects of pravastatin against the development of coronary atherosclerosis. METHODS: In 56 patients with stable CAD, 3-dimensional intravascular ultrasound was performed in matched coronary segments at the baseline and after 6-month treatment with pravastatin. RESULTS: The plaque volume was significantly reduced by 11% after treatment (p<0.001 vs. baseline). The percent plaque volume was positively correlated with the baseline BMI (r=0.37, p<0.001), and negatively correlated with the serum total cholesterol / high-density lipoprotein cholesterol ratio (r=0.27, p<0.05) and total leukocyte count (r=0.27, p<0.05). Multivariate regression analysis showed that BMI was an independent predictor of the change in plaque volume (beta coefficient: 0.326; 95% CI: 0.003 to 0.037; p<0.05). No correlations were found between BMI and changes in the serum levels of any other lipids, apolipoproteins, or hs-CRP. CONCLUSION: The present study demonstrated that an increase in BMI attenuated pravastatin-induced coronary atherosclerosis regression. The results may provide new insight into the framework for the treatment of obese patients with CAD.

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.

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.

Efficacy of calcium channel blocker in the secondary prevention of myocardial infarction--retrospective analysis of the 10-year prognosis or coronary thrombolysis-treated patients.

BACKGROUND: Calcium channel blockers (CCBs) may have a positive influence on the long-term prognosis of Japanese patients with ischemic heart disease. METHODS AND RESULTS: The effect of nifedipine-retard (NR) (n=202) compared with that of non-CCB treatment (n=92) on the secondary prevention of myocardial infarction (MI) was retrospectively investigated in patients who had survived acute MI between 1987 and 1996. The primary endpoint was the occurrence of cardiac death or non-fatal MI. The median follow-up was 6.3+/-2.4 years. The incidence of cardiac events was 8.9% in the NR group and 14.1% in the non-CCBs group (p=0.14, odds ratio (OR): 0.584, 95% confidence interval (CI): 0.286-1,193). However, subanalysis revealed that NR significantly reduced the incidence of cardiac events in patients aged less than 55 years (4.2 vs 18.2%, p=0.016, OR: 0.180, 95%CI: 0.045-0.721) and those who did not smoke (8.6 vs 16.4%, p=0.048, OR: 0.462, 95%CI: 0.203-0.999). CONCLUSION: Although this was a retrospective analysis, it showed that NR did not cause an increase in the incidence of cardiac events in post-MI patients; it even prevented cardiac events, especially in those who were less than 55 years of age and in non-smokers, suggesting the potential usefulness of CCBs in the secondary prevention of MI in Japan.

[Review of arrythmias related to acute myocardial infarction and its treatment].

Because reperfusion therapy for AMI has been widely performed, complicated fatal ventricular arrythmias related to AMI has been dramatically decreased. However, there still remain the incidence of fetal arrhythmias such as ventricular fibrillation(VF), ventricular tachycardia(VT) at the early phase in occurrence of AMI. Besides spreading bolus intravenous administration of mutant-tPA, Bystander CPR, Public access defibrillation (PAD), and setting of automated external defibrillators(AED) in the public facilities are actually required to reduce the mortality of AMI. In this article, we reviewed that arrhythmias associated with AMI and strategy for treatments of complicated arrhythmias in the clinical settings.