The long-term prognostic value of interleukin (IL)-18 in patients with ST-segment elevation acute myocardial infarction (STEMI) has been conflicting. Thus, the purpose of this study was to test whether the level of interleukin-18 measured on admission can predict long-term adverse clinical events in patients with STEMI who were undergoing percutaneous coronary intervention (PCI).
We recruited 288 consecutive STEMI patients (210 men, average age [71.42 ± 10.32] years) with onset < 6 hours who were undergoing primary PCI, and 148 age- and gender-matched control subjects. Plasma levels of IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) in all subjects. The patients with STEMI were then followed prospectively over 434 days (range, 0 to 642 days) for the occurrence of composite major adverse clinical events (MACE) (cardiac mortality, recurrent myocardial infarction, or readmission due to advanced heart failure). Patients with STEMI exhibited higher levels of plasma IL-18 (P < 0.001) compared with the control subjects. Positive correlations between IL-18 and cardiac troponin-I (cTnI) (r = 0.353, P = 0.0004) and IL-18 and high-sensitivity C-reactive protein (hs-CRP) (r = 0.420, P < 0.001) were observed by Spearman’s correlations analysis. Logistic regression analysis demonstrated that IL-18 ≥ 450 pg/mL (OR 10.854, 95% CI 2.328 to 50.594, P < 0.0001) was a significant independent predictor of composite MACE at 60 days. Cox regression analysis demonstrated that high plasma IL-18 levels were not correlated with the occurrence of long-term composite MACE.
The level of plasma IL-18 on admission may predict 60-day adverse clinical outcome, but not the long-term adverse clinical events in patients with STEMI undergoing PCI, and may be useful for mid-term risk stratification.

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To determine whether the initial degree of coronary narrowing prior to a first myocardial infarction (MI) affects left ventricular function, we analyzed paired coronary angiograms and left ventriculography in 41 consecutive MI patients in whom coronary angiography was obtained before and after MI.
Patients were divided into 2 groups according to coronary narrowing of the infarct culprit lesion at first angiogram; a significant narrowing group (group S, 15 patients) and a nonsignificant narrowing group (group N, 26 patients). Significant narrowing was defined as more than 75% stenosis of an infarct-related segment in the first angiography and nonsignificant narrowing was less than 50% narrowing. Clinical characteristics were similar in the two groups, with the exception of initial diameter stenosis. LV function was normal in both groups at initial examination. Group S patients had a higher prevalence of angina prior to MI (73% versus 23%; P = 0.001), good collateral development (73% versus 35%; P = 0.02), and non-Q MI (73% versus 27%; P = 0.004) than group N patients. RWM was also superior in group S compared with group N. The deterioration of global and infarction zone function was mild in group S compared with group N (group S; median EF -10%, RWM -0.27 SD/chord, group N; median EF -26%, RWM -1.62 SD/chord, P = 0.001).
We conclude that deterioration of LV wall motion in patients with severe stenosis in their initial stenosis would be milder than in AMI that developed from a mild degree of stenosis.

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Bilirubin has been considered an antioxidant, with capacity to remove reactive species of oxygen. Studies have suggested that an increased bilirubin level promotes protection against atherosclerosis.
The case group was composed of 100 patients with coronary artery disease and the control group 100 patients with normal coronaries. Blood samples were collected to determine bilirubin concentrations. Bivariate analysis, multiple logistic regression models, and Spearman’s correlation index were performed. A P value < 0.05 was considered to be significant.
The case group was predominantly composed of men and the control group of women, with a mean age of 60 ± 8.8 versus 56 ± 10.9 (P = 0.015). The total bilirubin average was significantly higher in the control group than in the case group (0.76 mg/dL versus 0.39 mg/dL, P < 0.001). The level of ultrasensitive C reactive protein (us-CRP) was increased in the case group (3.63 mg/L versus 0.93 mg/L, P < 0.001). Although the correlation index for this inverse association has been weak, both are independently associated with a higher prevalence of coronary artery disease, total bilirubin ≤ 0.56 mg/dL (OR: 10.04; IC: 3.48-28.90; P < 0.001), and ultrasensitive C reactive protein > 3 mg/L (OR: 1.17; IC: 1.04-1.33; P = 0.009).
Reduced serum levels of bilirubin were shown to be associated with a higher prevalence of coronary artery disease emerging as a new potential risk factor marker. Additional studies are still necessary to confirm and demonstrate the association of these findings with clinical outcomes.

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There is little information about long-term (> 1 year) outcomes after sirolimus-eluting stent (SES) implantation in dialysis patients. Percutaneous coronary intervention (PCI) using SES was performed in 63 dialysis patients with 77 lesions. A control group for comparison was composed of 45 consecutive dialysis patients with 62 lesions who received PCI using bare metal stents (BMS). Clinical follow-up duration was 21.7 ± 8.4 months in the SES group and 32.1 ± 9.2 months in the BMS group (P < 0.01). There was no significant difference in the in-segment restenosis rate (30% versus 40%, P = 0.20) between the 2 groups. The 3-year mortality (22.5% versus 22.2%, P = 0.75), myocardial infarction (3.8% versus 4.9%, P = 0.93), target lesion revascularization (24.7% versus 31.0%, P = 0.61), and stent thrombosis rates (3.8% versus 2.4%, P = 0.73) were not significantly different between the SES and BMS groups. Compared to BMS, SES do not improve long-term clinical outcomes in dialysis patients.

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We evaluated the efficacy of antiarrhythmic drug therapy (AAD) and long-term cardiovascular prognosis in patients with asymptomatic paroxysmal atrial fibrillation (AF). This retrospective study included 334 patients (229 men and 105 women, mean age, 69 ± 11 years, mean follow-up, 60 ± 11 months) who were divided into two groups; patients with symptomatic AF (group I) and those with asymptomatic AF (group II) on the basis of subjective symptoms.
(1) Actuarial rates of patients without AF recurrence, those with AF recurrence and with electrical/pharmacological cardioversion to restore sinus rhythm, and those with conversion to permanent AF despite AAD were 40%, 41%, and 19%, respectively, in group I, and 22%, 24%, and 54%, respectively, in group II at the end of the follow-up period. At 60 months, the percentage of patients with conversion to the permanent form of AF was significantly greater in group II than in group I (P < 0.05, group I versus group II). (2) Survival rates free from symptomatic thromboembolism at 36, 60, and 120 months were 96%, 93%, and 88%, in group I, and 82%, 76%, and 71%, respectively, in group II (P < 0.05, group I versus group II). In patients not undergoing anticoagulant therapy, the annual rate of symptomatic thromboembolism was significantly greater in group II (5.3%) than in group I (2.3%) (P < 0.05), while in patients undergoing anticoagulant therapy there was no significant difference in the annual rate of symptomatic thromboembolism between group I (0.9%) and group II (1.8%).
The clinical course of asymptomatic paroxysmal AF is refractory to AAD when compared to symptomatic AF, meaning that anticoagulant therapy is required to prevent symptomatic thromboembolism in this group.

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Analysis of short-term (5-minute) heart rate variability (HRV) may provide useful information about autonomic nervous control of the cardiovascular system. The aim of the present study was to evaluate the association between the results of treadmill exercise testing (TET) and short-term (5-minute) HRV. Patients undertaking TET were anteriorly evaluated with short-term (5-minute) HRV over time (SDNN, RMSSD, NN50 count, pNN50) and frequency (LF, HF, total power) domains. Among 414 patients, 32 individuals (7.7%; 14 men) had nondiagnostic results. The nondiagnostic group had older age, higher body mass index, more hypertension, lower SDNN, lower LF, and higher HF than the negative group. After adjustment for potential confounders, SDNN (OR 0.94, 95% CI 0.91-0.97; P = 0.01), RMSSD (OR 0.96, 95% CI 0.93-0.99; P = 0.02), NN50 count (OR 0.98, 95% CI 0.97-1.00; P = 0.04) and LF (OR 0.96, 95% CI 0.96-0.99; P = 0.03) were negatively related to nondiagnostic results, and HF showed a positive effect (OR 1.04, 95% CI 1.01-1.05; P = 0.02). No HRV indices were significantly associated with positive results. Our study suggested that cardiac autonomic indices derived from short-term HRV recordings might predict nondiagnostic results of TET.

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It is well known that peak oxygen consumption and heart rate (HR) recovery after exercise obtained from the cardiopulmonary exercise test are prognostic parameters in patients with chronic heart failure (CHF). However, it is unclear whether exercise-induced parameters obtained from the routine exercise stress test predict mortality in patients with CHF.
We studied 136 patients (93 males/43 females) with CHF. All patients underwent symptom-limited exercise stress testing. Exercise parameters included exercise duration, exercise-induced HR and systolic blood pressure (SBP), and metabolic equivalents (METs).
During the follow-up period (mean 6.2 years), 34 patients died. Survival rates at the 3rd and 5th years were 90% and 83%, respectively. Body mass index was significantly smaller in the nonsurvival group than in the survival group (P < 0.01). The incidence of patients with New York Heart Association III class was higher in the nonsurvival group than in the survival group (P < 0.05). In univariate analysis, predictors of mortality included peak HR and SBP, increases in HR and SBP during exercise, HR and SBP at the 1st minute after exercise, HR at the 3rd minute after exercise, and METs. The use of β-adrenergic blocking agents was not associated with prognosis. In Cox hazard model analysis, the increase in SBP (P < 0.002), HR at the 3rd minute after exercise (P < 0.05), and METs (P < 0.05) were independent predictors of mortality.
SBP response to exercise, HR recovery after exercise, and METs obtained from the routine exercise test predicted mortality in patients with CHF irrespective of the use of β-adrenergic blocking agents.

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Although extracorporeal membrane oxygenation (ECMO) is widely used as temporary circulation support, there are no reports of direct parameters indicating cardiac recovery to determine the timing of weaning off.
Twenty-five patients supported by ECMO due to hemodynamic deterioration were divided into 2 groups according to their outcome: weaned ECMO (W: n = 18) or not (NW: n = 7). In the W group, we examined the differences in parameters between the 2 time points, ECMO introduction, and the reduction in ECMO flow to 40% of the initial setting known as the conventional recovery point (C-point). Significant differences were observed in systolic pulmonary artery pressure, the cardiac index measured by the thermodilution method, C-reactive protein, lactate, base excess, and the end-tidal CO₂ concentration (ETCO₂). Next, by closely examining these 6 parameters measured every 12 hours, we found that only ETCO₂ had always changed steeply, like a ‘flexion point’ (E-point), in all W cases, but not in NW. The E-point was defined as an initial increase in ETCO₂ of ≥ 5 mmHg over the preceding 12 hours with a continued rise over the next 12 hours. E-points appeared as much as 95 ± 60 hours earlier than C-points and also preceded weaning off of ECMO.
ETCO₂ can be a useful continuous parameter for predicting the adequate timing of weaning off of ECMO for circulatory failure at the bedside.

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Recent evidence indicates that oxidative stress might actively participate in the pathophysiology of hypertension, atherosclerosis, and other cardiovascular diseases. The purpose of the present study was to assess the possible link between oxidative stress and membrane fluidity in hypertensive and normotensive men. We measured the membrane fluidity (a reciprocal value of membrane microviscosity) of red blood cells (RBCs) in hypertensive and normotensive men using an electron spin resonance (ESR) and spin-labeling method. Membrane fluidity of RBCs was decreased in hypertensive men compared with normotensive men. The levels of plasma 8-Iso-prostaglandin F2α (8-Iso-PG F2α : an index of oxidative stress) were significantly higher in hypertensive men than in normotensive men. In contrast, plasma nitric oxide (NO)-metabolite levels were significantly lower in hypertensive men than in normotensive men. In the overall analysis of hypertensive and normotensive men, plasma 8-Iso-PG F2α levels were inversely correlated with plasma NO-metabolites. Furthermore, the reduced membrane fluidity of RBCs was associated with increased plasma 8-Iso-PG F2α and decreased plasma NO-metabolite levels. In a multivariate regression analysis, plasma 8-Iso-PG F2α was found to be an independent determinant of membrane fluidity of RBCs. The results of the present study suggest that oxidative stress might have a close correlation with the rheologic behavior of RBCs and the microcirculation in hypertensive men.

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During oxidative cardiac metabolism, the myocardium produces reactive oxygen species, such as superoxide and hydrogen peroxide (H₂O₂). We hypothesized H₂O₂ is a coronary metabolic dilator linking regulation of coronary tone with myocardium metabolism. Dilation of isolated, pressurized coronary arterioles (76 ± 10 μm, diameter) in reaction to supernatant collected from enzymatically isolated cardiac myocytes was measured. Isolated rat myocytes were stimulated electrically [unpaced or stimulated at 200, 400 beats/min (bpm)]. H₂O₂ was significantly generated by pacing (400 bpm n = 11, 9.3 ± 0.4 μM P < 0.01, versus unpaced) and the addition of this supernatant caused vasodilation (500 μL to 2 mL bath, 14.6 ± 0.7%, P < 0.01 versus unpaced). Supernatant from unpaced myocytes was not vasoactive. To clarify the source of H₂O₂, myocytes were also stimulated at 400 bpm following treatment with Mn-TBAP (25 μM), which mimics the action of Mn-SOD, and apocynin (3 mM), an NADPH oxidase inhibitor (n = 11, each). Mn-TBAP increased H₂O₂ generation in myocyte supernatant stimulated at 400 bpm (12.2 ± 0.8 μM, P < 0.01 versus 400 bpm stimulation only). Treatment of the myocytes with Mn-TBAP augmented vasodilation by the stimulated myocyte supernatant (19.6 ± 1.1%, P < 0.01 versus untreated myocyte supernatant). Apocynin did not alter vasodilation to myocyte supernatant. These results suggest that the main source of superoxide by metabolic stimuli is cardiac myocytes and Mn-SOD is a scavenger from superoxide to H₂O₂. We conclude that H₂O₂ is a key metabolic vasodilator produced by myocardium.

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Lysophosphatidylcholine (LPC) is a proinflammatory and proatherogenic substance, and it plays an important role in the initiation, progression, and destabilization of atherosclerotic plaques. If LPC in the vascular wall is visualized in vivo, the mechanisms of atherosclerosis and the effects of medical and interventional therapies on atherosclerosis can be objectively evaluated. Therefore, this study was carried out to visualize LPC in human coronary plaques using a color fluorescence angioscopy (CFA) system.
(1) The fluorescence characteristics of LPC were investigated by color fluorescence microscopy (CFM) using Trypan blue dye (TB) as an indicator. For fluorescence imaging, a combination of a band-pass filter (345 nm) and a band-absorption filter of 420 nm (A imaging), or a combination of a band-pass filter (470 nm) and a band-absorption filter of 520 nm (B imaging) was employed. (2) The fluorescence of LPC in the excised human coronary plaques was investigated by CFA and CFM scanning using the same filters as those in CFM.
In the presence of TB, LPC exhibited a red fluorescence in both A and B imaging. This red fluorescence color in both A and B imaging was not observed for the other known major substances that constitute the atherosclerotic plaques. This red fluorescence color in both A and B imaging was detected by CFA in both white and yellow plaques that were classified by conventional angioscopy. This fluorescence color was found to be distributed in a web-like or diffuse configuration by CFM scanning.
LPC in the human coronary plaques was successfully visualized by CFA using TB as an indicator.

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A 49-year-old man presenting with ST-elevated myocardial infarction was brought to our emergency department with AL amyloidosis. Baseline coronary angiography showed no significant stenosis of the epicardial coronary arteries, however, coronary artery angiography in response to acetylcholine and coronary flow reserve in response to papaverine were abnormal, which suggested impairment of vascular endothelial function. Myocardial biopsy revealed amyloid deposition exclusively in intramural coronary arteries. Early amyloidosis without myocardial involvement can produce acute coronary syndrome through the combination of spastic epicardial coronary arteries and obstruction of the intramural coronary arteries. In the management of certain patients with acute coronary syndrome, the possibility of cardiac amyliodosis should be taken into consideration.

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The transradial approach for coronary diagnostic and therapeutic interventions is a well-established, safe, and effective technique that has shown a success rate comparable to that of the transfemoral approach for chronic total occlusion (CTO) with less access site complications. Recently, the transulnar approach was also found to be a safe and feasible alternative for diagnostic and percutaneous coronary intervention (PCI). There is limited data on the efficacy and safety of the transulnar approach for CTO PCI. Here, we report the case of a patient who underwent coronary intervention for CTO via the bilateral ulnar approach.

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Trastuzumab-related cardiac dysfunction may be manageable and completely reversible with suitable cardiac medication, allowing optimal breast cancer treatment to continue. We present the case of a 42-year-old woman who developed severe systolic left ventricular failure with impaired contractility of the right ventricle, pulmonary hypertension, and clots in the left ventricular cavity during adjuvant treatment for breast cancer. The patient was initially diagnosed with early breast cancer and underwent surgery on her left breast. She received 6 cycles of anthracycline chemotherapy followed by radiation therapy in the left breast area, then 5 cycles of trastuzumab. After the fifth cycle of trastuzumab, she experienced dyspnoea and leg edema. Fluid was detected in the pleural cavities but no lung metastases were identified. Echocardiography was performed, revealing a severely reduced left ventricular ejection fraction (10%) with impaired contractility of the right ventricle and pulmonary hypertension. Standard medication for heart failure resulted in complete recovery of normal systolic and diastolic function of the left and right ventricles. The combination of low molecular weight heparin and acetylsalicylic acid completely resolved the thrombotic complications. The patient regained her full range of social, occupational, and family activities. This case study is the first to demonstrate the manageability and reversibility of trastuzumab-related cardiac complications in a patient who had developed severe heart failure complicated with left ventricular thrombosis during sequential anthracycline and trastuzumab therapy for breast cancer. The findings contradict other opinions that trastuzumab-related acute heart failure is analogous to stunning or hibernation and recovers without specific cardiac treatment.

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