Inflammatory cytokines are important for both cardiovascular scientists and practicing clinicians. Interleukin-6 (IL-6) has been emphasized by reports of elevated circulating as well as intracardiac IL-6 levels in patients with congestive heart failure (CHF). IL-6 may contribute to the progression of myocardial damage and dysfunction in chronic heart failure syndrome resulting from different causes. As the cause of CHF in cardiomyopathy, myocarditis, allograft rejection, and left ventricular assist device (LVADs) conditions, circulating IL-6 levels are associated with the severity of left ventricular dysfunction, and are also strong predictors of subsequent clinical outcomes. Continuous and excessive production of IL-6 promotes myocardial injury by breaking down both cytokine networks and viral clearance under viral myocarditis. Although IL-6 is likely important in the process of viral antigen presentation, early activation of immune responses and attenuation of viral replication also appear to be significant in an animal model of viral myocarditis. IL-6 can cause cardiac hypertrophy through the IL-6 signal transducing receptor component, glycoprotein 130. There are several interesting cases of cardiac myxoma complicated with mediastinal lymphadenopathy or left ventricular hypertrophy. Increased expression of IL-6 is observed in the myocardium of all donor hearts showing marked dysfunction. Myocardial IL-6 concentrations are also significantly higher in LVAD candidates compared with advanced heart failure patients. Although the IL-6 family plays a central role in the pathophysiology of cardiovascular diseases, it remains to be determined whether the IL-6 family is beneficial or detrimental. Future study will be needed to resolve this question.
The optimal diagnostic approaches using contractile reserve, perfusion, and free fatty acid metabolism together for identifying myocardial stunning after reperfusion have not been clarified in the clinical setting. We investigated the usefulness of simultaneous evaluation of these parameters during myocardial stunning to predict the functional recovery in infarct-related myocardium after reperfusion. In 43 patients (60.7 ± 10.4 years) with successful coronary angioplasty early after a first myocardial infarction, low-dose (5 to 10 μg/kg/min) dobutamine stress thallium-201/iodine-123 β-methyl-iodophenyl pentadecanoic acid (BMIPP) dual-isotope single photon emission computed tomography was performed with echocardiography in the acute phase within 1 week after reperfusion. Regional wall motion and the uptake of each tracer were obtained simultaneously in the infarct-related segments. In 93 segments with dyssynergy in the acute phase after reperfusion, the sensitivity, specificity, and accuracy using contractile reserve for predicting the final functional recovery in the chronic phase more than 3 months after PTCA were 81.3%, 67.2%, and 72%, respectively. More accurate predictions were obtained by simultaneous measurements of thallium-201 and BMIPP uptakes (93.8%, 66.7%, and 79.4%, respectively). The final functional recovery in the stunned myocardium after early reperfusion following acute myocardial infarction was predicted more accurately by simultaneous evaluation of these parameters at dobutamine stress testing.
Immune-mediated mechanisms are thought to play a key role in the development of coronary artery disease and its thrombotic complications. Preinfarction angina has been suggested to improve left ventricular function and short-term outcomes. The purpose of the present study was to investigate the relation between the immune response and in-hospital clinical course in preinfarction angina. We prospectively evaluated 93 patients. Forty-three patients exhibited preinfarction angina within 24 hours before the onset of acute myocardial infarction (AMI) (preinfarction angina group) and 50 patients were free from preinfarction angina (sudden onset group). The incidence of complications (heart failure, recurrent angina, arrhythmia and coronary interventions) and in-hospital mortality were assessed in the two study groups. We detected some immune markers, including white blood cells, C-reactive protein, immunoglobulins, and complement. White blood cells and CRP were significantly lower in the preinfarction angina group than in the sudden onset group (P < 0.001, P < 0.005, respectively). Conversely, IgE and C4 were significantly higher in the preinfarction angina group than in the sudden onset group (P < 0.001, P < 0.001, respectively). The incidences of heart failure and severe arrhythmias were lower in the preinfarction group than in the sudden onset group (P < 0.005, P < 0.05 respectively). The beneficial effect of preinfarction angina may be associated with an immune-inflammatory response modified by a brief ischemic episode.
In the present study, we evaluated whether stenting is useful for cardiac overloading, using ANP, BNP, and 99mTc-tetrofosmin myocardial scintigraphy. It has been reported that coronary artery stenting is useful for cardiac functions for acute myocardial infarction (AMI). The subjects were 110 patients with AMI successfully treated by direct angioplasty. These patients were subgrouped into two groups: the S group (underwent stenting; 54 patients) and the P group (underwent POBA alone; 56 patients). Extent scores reflecting decreased myocardial blood flow were calculated at myocardial areas showing a radioactivity count of less than -2 × standard deviations compared to the database of normal subjects.The ratio of extent scores to defect scores (extent/defect ratio) was compared between the P and S groups. Both ANP and BNP levels in the S group were lower than in the P group at the chronic stage (1 and 3 months after reperfusion therapy). Moreover, the end-diastolic volume index from the left ventriculography 3 months after reperfusion therapy was significantly larger in the P than the S group. The extent/defect ratio was significantly lower in the P group (2.8 ± 0.2) than the S group (3.5 ± 0.3), suggestive of a microcirculation disorder. These results suggest that cardiac overloading and left ventricular remodeling are decreased more by stenting than by POBA alone, probably because stenting prevents decreased myocardial blood flow around the infarct myocardium.
Aortic pulse wave velocity (PWV) is a predictor of atherosclerosis. The percent mean pulse amplitude of the artery (%MPA) has been proposed as a novel marker of atherosclerosis. The present study evaluated the predictive value of PWV and the %MPA for coronary atherosclerosis. The severity of coronary atherosclerosis was evaluated using both the Gensini score and coronary calcium grade. Thirty-three patients with cardiovascular risk factors were assigned to those with significant coronary artery stenosis (+stenosis) group with the presence of ≥ 75% coronary artery stenosis (n = 15; age: 68 ± 7 years, mean ± SD) or those without significant coronary artery stenosis (-stenosis) group (n = 18; age: 66 ± 8 years). In each patient, the PWV and %MPA at the right brachial artery and both sides of the ankle were obtained using a non-invasive vascular screening device. The Gensini score and coronary calcium grade were higher in the +stenosis group than they were in the -stenosis group (P < 0.01 and P < 0.05, respectively). The brachial %MPA was lower in the +stenosis group than it was in the -stenosis group (P < 0.005). Both the Gensini score and the coronary calcium grade correlated with the brachial %MPA (r = 0.62, P = 0.0001 and P = 0.33, P = 0.030, respectively). Our observations suggest that brachial %MPA provides predictive values for coronary atherosclerosis in subjects at risk for cardiovascular disease.
We studied the long-term follow up of abnormal T wave morphology (notched, low amplitude, and inverted T waves) of five female patients with LQT2 (HERG) mutations. The patients, aged 43, 19, 27, 26, and 56 years, had experienced syncopal attacks and were followed up for 3-17 years (average 9.4 years). Patients were treated with a β-blocker alone (2) or combined with other drugs (3). The mutation in four patients was missense (A614V, T613, E130K) and its location was the pore region (3) or between the S1 transmembrane region and N-terminal (one). The fifth patient had an intragenic deletion (49 bp deletion) at HERG exon 4 (S1 transmembrane region and N-terminal), which was not identified as having any mutation. The patients manifested a notched T wave in at least one left precordial or limb lead (I, II or aVF). A low T wave amplitude was shown in at least one lead, and deeply inverted or biphasic waves in right precordial leads were also associated with these findings. The abnormal T wave finding in any of the 12 leads in our 5 LQT2 patients was shown to be widespread and was always found during the long-term follow up. The present cases suggest that notched T waves are useful for diagnosing female symptomatic LQT2 patients.
Symptom-limited cardiopulmonary exercise testing was performed in 37 patients with mitral stenosis (MS) without significant coronary artery stenosis to evaluate factors affecting ST depression in exercise electrocardiograms. The degree of ST depression was not associated with gender or exercise tolerance. The incidence of significant ST depression was higher in the patients receiving than in those not receiving digitalis (P < 0.05). In addition, the patients with atrial fibrillation and a higher heart rate response were more likely to have a high prevalence of significant ST depression than those with sinus rhythm and a lower response (P < 0.05). We concluded that atrial fibrillation, a higher maximum heart rate, and oral digitalis administration were involved in ST depression during exercise testing in patients with mitral stenosis without coronary heart disease.
Multiple intracardiac catheters are often necessary for electrophysiological study (EPS) and radiofrequency (RF) ablation therapy. Therefore, multiple venous sheath placement in one femoral vein is always required for multiple intracardiac catheter insertion. The vascular complications incurred by placement of multiple sheaths have not been fully studied. We utilized duplex ultrasonography to assess the femoral veins before and after the procedure. This study consisted of 52 patients (68 femoral veins) who underwent EPS and RF ablation therapy. Up to three sheaths were inserted into a single femoral vein. Nonocclusive deep vein thrombosis (DVT) occurred in 12/68 veins (17.6%) of 11 patients on the day following the procedure. Thrombosis regressed spontaneously in 11 veins and persisted in 1 vein at 1-week follow-up. The venous diameter significantly decreased the day after the procedure (8.7 ± 1.2 mm vs 5.3 ± 1.5 mm, P < 0.001), but recovered by the 1-week follow-up (7.9 ± 1.7 mm, P = 0.07) in the 12 veins. Short-term placement of multiple venous sheaths in a single femoral vein appears to be safe. Nonetheless, nonocclusive DVT does occur in a significant number of patients. Although thrombosis regressed and the outcome appeared to be benign in most patients, close follow-up to avoid potential vascular complications is necessary.
Controversy exists about the influence of patient age on the benefit of surgery in atrial septal defect (ASD). Tissue Doppler echocardiography (TDE) when applied to atrioventricular annuli provides variables reliably reflecting the performance of the corresponding ventricle. We sought to investigate the effect of timing of surgery on biventricular functions by comparing the conventional echocardiography variables and TDE profiles of right and left atrioventricular annuli in patients treated at various ages. Conventional echocardiography and TDE analysis of mitral and tricuspid annuli were performed in 20 controls and 61 patients who underwent surgical ASD closure 2.8 ± 2.5 years before the study. Standard parameters included were right and left-sided dimensions, estimated pulmonary artery pressure, ejection fraction, and tricuspid annular motion amplitude. TDE variables were systolic, early and late diastolic peak velocities at tricuspid lateral-and mitral-annulus at lateral and septal corners. Two subsets of patients who underwent surgery before (group 1, n = 20) and after 25 years (group 2, n = 41) formed our subgroups. Peak systolic TDE velocity and tricuspid annular motion amplitude had the lowest value in group 2 (P < 0.01 and <0.02, respectively). Late diastolic TDE velocity was significantly lower in group 2 compared to group 1 (P < 0.05). Increased right ventricular and atrial dimensions (P < 0.001 for both) and the estimated pulmonary artery pressure (P < 0.03) were the conventional measurements discriminating group 2 from group 1. The TDE profile of the mitral annulus was similar between the groups. These results suggest that delayed ASD closure is a relatively less effective procedure to restore secondary right ventricular dysfunction, as demonstrated by significantly different TDE measurements reflecting right ventricular longitudinal contraction and relaxation.
This prospective study was designed to evaluate the prognostic value of the percentage of plasma lymphocytes in patients with diastolic dysfunction as well as systolic dysfunction of the left ventricle. The subjects were 70 consecutive patients who were hospitalized in our institution from April 2001 to August 2002. Following the improvement of congestive heart failure, leukocyte differentiation and neurohumoral factors (plasma levels of atrial and brain natriuretic peptide, norepinephrine, epinephrine, and dopamine) were measured. During the follow-up period (17 ± 9 months), 18 patients experienced a cardiac event. In the univariate analysis, the percentage of plasma lymphocytes in the cardiac event group was significantly less than that in the noncardiac event group (24.7 ± 8.40 vs 33.3 ± 7.64%, P = 0.0006), and brain natriuretic peptide was significantly larger in the cardiac event group (402 ± 168 vs 153 ± 51 pg/mL, P = 0.04). However, in patients with preserved systolic function, there was a significant difference in the percentage of plasma lymphocytes between the cardiac and noncardiac event groups (21.7 ± 9.42 vs 34.2 ± 8.21%, P = 0.037), although no difference was observed in brain natriuretic peptide (133 ± 43 vs 125 ± 50 pg/mL, P = 0.87). Multivariate analysis showed the percentage of plasma lymphocytes was an independent predictor of a cardiac event. The percentage of plasma lymphocytes may be useful for predicting the course of patients with congestive heart failure based on diastolic dysfunction as well as systolic dysfunction.
Differences in structural remodeling are believed to be influenced by hormonal systems in hypertension. The objective of the present study was to investigate the change in the circulating catecholamine β-adrenergic system in the left ventricle remodeling process in hypertensives. One hundred and thirty-four men (mean age, 53 years) had essential hypertension and underwent echocardiography before treatment. Normal morphology (n = 26) and concentric remodeling (n = 41) were defined by a relative wall thickness at diastole (RWT) of < 0.44 and ≥ 0.44, respectively, and concentric hypertrophy (n = 28) and eccentric hypertrophy (n = 39) by a left ventricular mass index (LVMI) of < 150 g/m2 and ≥ 150 g/m2, respectively. Forty healthy males were studied as normal controls. Plasma levels of norepinephrine (NE) and epinephrine (E) were measured by high performance liquid chromatography. The density of lymphocyte β-adrenoceptors (β-AR) and the content of intralymphocyte cyclic AMP (cAMP) in peripheral blood were measured using 3H-dihydroalpneol as a ligand and protein binding assay, respectively. The plasma levels of NE and E in the 4 groups of patients with essential hypertension were significantly increased compared with the control group. The density of lymphocyte β-AR and the content of intralymphocyte cAMP of peripheral blood in the normal morphology, concentric remodeling, and concentric hypertrophy groups were significantly higher than those in the control group, while the values in the eccentric hypertrophy group were significantly lower than those in the control group. Among the 4 groups, the plasma levels of NE and E had increased the most in the normal morphology group, followed in decreasing order by the concentric remodeling, concentric hypertrophy, and eccentric hypertrophy groups; the density of lymphocyte β-AR and the content of intralymphocyte cAMP of peripheral blood in the normal morphology, concentric remodeling, and concentric hypertrophy groups increased while they decreased in the eccentric hypertrophy group in patients with essential hypertension. The catecholamine β-adrenergic system appears to be related to left ventricular remodeling of hypertension. In this process, catecholamines increased continually. The density of β-AR and the content of cAMP in peripheral lymphocytes increased at first and then decreased.
We have reported that repeated sauna therapy improves impaired vascular endothelial function in a patient with coronary risk factors. We hypothesized that sauna therapy decreases urinary 8-epi-prostaglandin F2α (PGF2α) levels as a marker of oxidative stress and conducted a randomized, controlled study. Twenty-eight patients with at least one coronary risk factor were divided into a sauna group (n = 14) and non-sauna group (n = 14). Sauna therapy was performed with a 60°C far infrared-ray dry sauna for 15 minutes and then bed rest with a blanket for 30 minutes once a day for two weeks. Systolic blood pressure and increased urinary 8-epi-PGF2α levels in the sauna group were significantly lower than those in the non-sauna group at two weeks after admission (110 ± 15 mmHg vs 122 ± 13 mmHg, P < 0.05, 230 ± 67 pg/mg • creatinine vs 380 ± 101 pg/mg • creatinine, P < 0.0001, respectively). These results suggest that repeated sauna therapy may protect against oxidative stress, which leads to the prevention of atherosclerosis.
Restenosis after stent deployment remains a major clinical problem. Antioxidants have been proposed as a promising strategy against restenosis. We tested the antioxidant probucol for its efficacy against neointimal hyperplasia in porcine coronary arteries after stent implantation. Probucol was then tested in vivo in 8 coronary arteries of 4 pigs (1000 mg/day orally beginning 7 days before stenting) and was compared to placebo (10 coronary arteries, 5 pigs) 28 days after stenting. Quantitative intravascular ultrasound (IVUS) revealed 38.8 ± 4.0 versus 40.1 ± 3.0% area stenosis in the probucol versus control group. Histopathologic assessment showed that probucol had no beneficial effect on inhibiting the neointimal proliferative response in stent lesions compared to placebo (2.35 ± 0.26 versus 2.88 ± 0.25 mm2), despite similar injury scores (1.20 ± 0.12 versus 1.28 ± 0.14). An edge segment (axially 2-mm proximal to the stent margins) was assessed by IVUS. Remodeling index, which is a good marker of constrictive remodeling, was defined by the ratio of the vessel area in the lesion site (stent edge) to the vessel area in the proximal reference site (6-mm proximal to the stent margins). The remodeling index was significantly larger in the probucol group that in the placebo group (1.18 ± 0.10 versus 0.90 ± 0.06, P = 0.0012). In conclusion, probucol reduced constrictive remodeling at the edge of the implant but did not inhibit the tissue response within the stent.
Nowadays, evidence-based medicine has entered the mainstream of clinical judgement and the human genome has been completely decoded. Even the concept of individually designed medicine, that is, tailor-made medicine, is now being discussed. Due to their complexity, however, management methods for clinical information have yet to be established. We have conducted a study on a universal technique which enables one to select or produce by employing information processing technology clinical findings from various clinical information generated in vast quantity in day-to-day clinical practice, and to share such information and/or the results of analysis between two or more institutions. In this study, clinically useful findings have been successfully obtained by systematizing actual clinical information and genomic information obtained by an appropriate collecting and management method of information with due consideration to ethical issues. We report here these medical achievements as well as technological ones which will play a role in propagating such medical achievements.
In addition to coronary atherosclerotic disease, coronary thromboembolism can also lead to acute coronary syndromes. However, coronary thromboembolism due to prosthetic heart valves is very rare and not very well-known. It has Only a few cases have been reported. In this paper, we present a rare case with vasospastic angina pectoris secondary to coronary thromboembolism in a patient with prosthetic heart valves.
Coronary artery aneurysm (CAA) is a rare disorder, characterized by abnormal dilatation of a localized portion or diffuse segments of the coronary artery. CAA may cause angina, myocardial infarction, sudden death due to thrombosis, embolisation, or rupture. In this report, a 63 year old Turkish male patient is presented who had an acute non-Q wave myocardial infarction due to spontaneous rupture of the left circumflex artery aneurysm. An extremely rare clinical presentation of rupture of a left circumflex CAA is discussed.
Single coronary artery is a rare congenital anomaly and is commonly associated with other congenital cardiac malformations. This report describes a 42-year-old man with an isolated single coronary artery, in whom the right coronary artery did not originate from the aorta but rather from the distal left circumflex artery. This patient did not have any other cardiovascular anomaly. However, he experienced angina pectoris and evidence of myocardial ischemia. Coronary angiography revealed insignificant coronary artery stenosis. He received medical treatment and responded well. An isolated single coronary artery is extremely rare, and this case may be only the 12th case reported in the literature.
We report a 64-year-old Turkish man who presented with unstable angina pectoris. Coronary angiography revealed massive intracoronary thrombus, which completely occluded the distal part of the left circumflex coronary artery. The thrombotic segment and the rest of the coronary tree were free of atherosclerosis. The patient was treated with intravenous tirofiban, a glycoprotein IIb/IIIa inhibitor. A control angiography was performed one week later and showed total dissolution of the thrombus with tirofiban therapy.
This case report describes three hypertrophic cardiomyopathy patients with abnormal His-Purkinje conduction and complete atrioventricular block with attacks of syncope and cardiopulmonary arrest. Although arrhythmias are common in hypertrophic cardiomyo-pathy, complete atrioventricular block is very rare. Prolonged QRS duration and abnormal His-Purkinje system conduction may result in complete atrioventricular block.
Brucellosis is a multisystemic disease. The most common cause of death from the disease is endocarditis. The aortic valve is most commonly affected. The disease rarely involves the mitral valve. A 30 year-old woman presented with complaints of chills and fever up to 38°C at night, fatigue, palpitations, and dyspnea for the previous 3 weeks. Cardiac auscultation revealed a diastolic murmur in the mitral area. Her temperature was 38.3°C. On echocardiographic examination, the mitral valve area was 0.62 cm 2 and an isoechoic mass thought to be a vegetation was detected on the anterior mitral leaflet. A diagnosis of infective endocarditis was made and vancomycin administration was commenced. Brucella melitensis was isolated in all three blood samples, however, the patient remained seronegative with Brucella agglutination titers of up to 1/160. The antibiotic therapy was then shifted to doxycycline (200 mg/day), rifampicin (600 mg/day), and ciprofloxacin (1000 mg/day). After 30 days of treatment, surgery was performed for the severely stenotic mitral valve and to remove the vegetation. The operation was successful. The postoperative period was uneventful. On the follow-up she had no complaints. In cases with Brucella endocarditis, after diagnosis, antibiotic therapy must be started immediately and when the clinical condition improves, surgical intervention should be performed when indicated.
A 51-year-old male presented with sudden onset lower abdominal pain followed by weakness of both legs. Examination revealed blood pressure of 220/130 mmHg, with a grade 2/6 systolic murmur audible at the apex of the heart, and absence of both femoral arterial pulses. Two-dimensional and transesophageal echocardiography showed no evidence of intracardiac tumor or dissection of the ascending and thoracic aorta. Moreover, an aortogram demonstrated total occlusion of the abdominal aorta just below the renal arteries. A myxomatous-like material occupying the abdominal aorta just above the bifurcation of the common iliac arteries was discovered during surgery. Histologic examination of the embolic material confirmed the diagnosis of myxomatous embolus. One year after the embolic episode, the patient was well and two-dimensional and transesophageal echocardiography revealed no evidence of residual intracardiac tumor.