Slow coronary flow (SCF) is the phenomenon of slow progression of angiographic contrast in the coronary arteries in the absence of stenosis in the epicardial vessels in some patients presenting with chest pain. There are no definite treatment modalities for patients with SCF. Our aim was to investigate the efficacy of nebivolol in patients with slow coronary flow by monitoring its effects on endothelial function and different markers of inflammation. Forty-two patients (16 females, 26 males; mean age, 55 ± 10) with slow coronary flow (SCF) were included in the study. After baseline assessment, the patients were administered nebivolol 5 mg once daily. After 12 weeks of nebivolol therapy, the biochemical and ultrasonographic examinations were repeated. Chest pain relief was detected in 38 patients after treatment (90%). Systolic and diastolic blood pressure and high sensitive CRP were significantly decreased after nebivolol therapy. Among brachial artery dilation variables that reflect endothelial function, basal resistive index (RI), post-flow mediated dilation RI, and post-nitrate mediated dilation RI were significantly decreased after therapy. Nebivolol is effective at improving endothelial function in patients with SCF. It controls chest pain, decreases CRP, and has favorable effects on brachial artery dilation variables in patients with coronary slow flow.

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The aim of the present study was to examine the antihypertensive and antihypertrophic effects of combined treatment with a long-acting calcium antagonist on top of an angiotensin II receptor blocker (ARB) in uncontrolled hypertensive patients. Patients with essential hypertension and a blood pressure > 140/90 mmHg on ARB monotherapy (losartan 50 mg/day or candesartan 8 mg/day) were randomly assigned to a nifedipine controlled release (CR) group (n = 15) or amlodipine group (n = 11). A significant additional antihypertensive effect was noted from 1 month with nifedipine and 2 months with amlodipine. The average daily dose was 25 mg for nifedipine and 5 mg for amlodipine. The cardiothoracic ratio was significantly reduced in both groups after 3 months. Left ventricular wall thickness and left ventricular mass index also decreased. Metabolic parameters, hepatic function, and renal function did not change significantly. Additional treatment with a long-acting calcium antagonist achieved further blood pressure reduction as well as an antihypertrophic effect in the uncontrolled patients with prior ARB monotherapy.

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Metabolic syndrome (MetS) includes some parameters which are associated with cardiovascular events and risk of developing heart failure (HF). The aim of the present study was to explore the prevalence of metabolic syndrome and individual MetS parameters among heart failure patients.
Stable HF patients who had an ejection fraction (EF) ≤ 35% were included. They were evaluated for MetS and parameters according to the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program (NCEP).
One hundred and nine patients (72 males, 37 females; mean age, 67 ± 12 years) were included. The most prevalent parameters were low HDL-C (69%) and hypertension (69%) in all participants. No significant change was observed in the prevalence of these parameters due to gender (P > 0.05). Hypertension, increased waist circumference, and hypertriglyceridemia were all significantly more common in women (P < 0.05). The prevalences of hypo-HDL-emia, hyperglycemia, and hypertension did not differ significantly with an advanced age (P > 0.05), whereas hypertriglyceridemia and high waist circumference were significantly decreased in the elderly (P < 0 05). The overall MetS prevalence was 51% and it was significantly higher in women (76% versus 37%, P : 0.003). The prevalence of MetS clearly decreased with age, although the difference was not statistically significant (61% versus 46%, P : 0.57). The mean number of positive MetS parameters also changed significantly with age (3 ± 1.4 versus 2.5 ± 1.3, P : 0.046). EF did not change with mean number of MetS parameters (P > 0.05).
Hypo-HDL-emia and similarly hypertension were the 2 most common MetS parameters in HF patients. Hypo-HDL-emia and hypertension were the most common parameters observed in all participants and no significant difference was seen due to gender or age. Even though the prevalence of MetS and the mean number of parameters were significantly more common in females and young patients, EF did not change with changes in these parameters. Based on the results obtained, we conclude that the early diagnosis and treatment of MetS as well as the measurement of individual parameters, especially the most frequent ones, may prevent heart failure or improve its status.

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Whole blood transfusion generates an inflammatory response and may contribute to organ dysfunction following cardiopulmonary bypass. We established a miniaturized (minimum 140 mL) and biocompatible bypass system to reduce perioperative inflammatory responses and avoid blood transfusions. This study was designed to reveal the influences of stored red blood cell (RBC) transfusions on perioperative inflammatory responses in infants.
Fifty-four consecutive patients weighing 4-10 kg who underwent surgical procedures for complex heart anomalies with asanguineous prime were retrospectively reviewed. Twenty-two patients (40.7%) received RBC transfusions during CPB. The postoperative peak white blood cell count (p-WBC), peak neutrophil count (p-NC), and peak C-reactive protein (p-CRP) were compared for both patient groups. Stepwise multiple logistic regression analyses were used to investigate which of the factors most affected the perioperative inflammatory responses.
The p-CRP and p-NC in patients with transfusion was significantly greater than those in patients without transfusion (CRP 8.1 ± 5.1 versus 5.5 ± 3.0 mg/dL, P < 0.05, p-NC 14.6 ± 4.5 versus 12.0 ± 4.0 × 1000/mm³, P < 0.05). Multivariate analyses showed that RBC transfusion most affected p-WBC (coefficient: 3.89, 95% confidence interval [CI] 0.79-6.99, P = 0.015) and p-NC (coefficient: 3.64, 95% CI 0.87-6.40, P = 0.011).
The RBC transfusions increased the perioperative inflammatory responses, compared to transfusion-free procedures, even when using a miniaturized biocompatible bypass with an asanguineous prime.

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The impact of heart failure with preserved left ventricular ejection fraction (LVEF) on activated hemostasis is still unclear. We sought to compare the activation of hemostasis in patients with heart failure with preserved LVEF, with impaired LVEF, and in healthy controls. Biomarkers of coagulation and fibrinolysis (D-dimer, tPA and PAI-1) were determined in outpatients with chronic stable (NYHA I-III), optimally managed heart failure with preserved LVEF (n = 46) and with impaired LVEF (n = 52), and in healthy age- and gender-matched controls (n = 14). In comparison to healthy controls, patients with heart failure and preserved LVEF had increased median D-dimer levels (606 [330-1222] μg/L versus 174 [86-249] μg/L; P < 0.001), and median PAI-1 (20 [15.3-33.1] μg versus 6.2[3.4-8.9] μg/L; P < 0.001) and tPA antigen concentrations (9.6 [8.1-13.3] versus 3.6 [2.2-5.0] μg/L; P < 0.001). However, unlike tPA and PAI antigens, D-dimer levels in preserved LVEF did not reach values as high as in impaired LVEF (917 [454-1185] μg/L; P = 0.013). Moreover, in patients with impaired LVEF, but not in those with preserved LVEF, age and NT-proBNP emerged as independent predictors of log-transformed D-dimer levels. Heart failure with preserved LVEF is associated with a procoagulant state as determined by increased levels of D-dimer, tPA and PAI-1 antigens. D-dimer levels are significantly higher in patients with impaired LVEF, while tPA and PAI-1 levels are increased regardless of LVEF.

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Sternal dehiscence following cardiac surgery has a multifactorial etiology. Significant risk factors contributing to sternal dehiscence include chronic obstructive pulmonary disease (COPD), obesity, or re-exploration due to bleeding or pericardial tamponade. We have focused on the role of allogeneic blood transfusion as a factor leading to the poor healing of surgical wounds.
A prospective observational study of 1553 elective and emergency cardiac surgery patients was performed between January 2003 and June 2007. All of the patients enrolled in this study underwent median sternotomy. We studied the relationship between sternal dehiscence following cardiac surgery and the total number of packed red blood cells transfused.
The incidence of sternal dehiscence in the study group was 3.4%. Diabetic patients did not have a higher incidence of wound dehiscence. Although COPD,²⁾ obesity,²⁾ and re-exploration⁴⁾ contributed to sternal dehiscence, the number of allogeneic blood transfusions during the perioperative period was an important independent risk factor for sternal dehiscence. Patients with sternal dehiscence received an average of 7.6 transfusion units (TU) of allogeneic blood versus 1.6 TU of allogeneic blood in the group without sternal dehiscence (P < 0.00005). The dehiscence affected patients without any other significant risk factor who received 6 or more TU, or patients with at least one significant risk factor who received 4 or more TU of allogeneic blood.
According to our results, the total amount of allogeneic blood transfused is an important risk factor contributing to sternal dehiscence. Regardless of other risk preconditions, the transfusion of 6 or more TU could result in sternal dehiscence following cardiac surgery.

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Prognosis of patients with heart failure (HF) remains unclear in Japan and should be determined in a prospective fashion. A prospective cohort of The Shinken Database comprised details on all of the new patients, including both inpatients and outpatients, who visited The Cardiovascular Institute Hospital in 2004-2005. HF patients were defined as those with symptomatic HF coexisting with structural heart diseases. Among 4,255 patients who visited our hospital, 597 patients (male/female 414/183, age 65.1 ± 12.9 years, LVEF 56.2 ± 18.0%) were diagnosed as presenting symptomatic HF. Ischemic heart disease was present in 305 (51.1%), valvular heart disease in 212 (35.5%), dilated cardiomyopathy in 59 (9.9%), hypertrophic cardiomyopathy in 24 (4.0%), hypertensive heart disease in 14 (2.3%), and others in 67 (11.2%). Hypertension, atrial fibrillation, and diabetes were observed in 35.3%, 27.4%, and 23.7%, respectively. During the mean follow-up period of 539 ± 257 days, 40 deaths (5.0% per year) occurred, including 34 cardiovascular deaths (4.5% per year, NYHA class II: 1.0%, III: 11.3%, IV: 36.6% per year, respectively). The present study showed that the prognosis of Japanese patients with HF among moderate to severe severity was found to be similar to that of Western countries. Multiple Cox hazard analysis identified the presence of chronic kidney disease and NYHA class as independent predictors for cardiovascular death. This prospective cohort study identified the prevalence, prognosis, and risk factors in HF patients to provide a basis for therapeutic management in Japan.

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Diabetes mellitus (DM) is clinically associated with an increased incidence of atrial fibrillation (AF), but the underlying mechanism remains unclear. We hypothesized that neural remodeling enhances AF vulnerability in diabetic hearts. Eight weeks after creating streptozotocin-induced diabetic rats (DM rats) or control rats, the hearts were perfused according to the Langendorff method. Inducibility of AF was evaluated by 5 times burst pacing from the right atrium and the atrial effective refractory period (AERP) was measured. The protocol was repeated during sympathetic nerve stimulation (SNS) or parasympathetic nerve stimulation (PNS). In tissue samples taken from the right atrium, the density of nerves positive for tyrosine hydroxylase (TH) and acetylcholinesterase (AChE) were determined. SNS significantly increased the incidence of AF in DM rats (14 ± 6 to 30 ± 8%, P < 0.01), but not in control rats (11 ± 4 to 14 ± 6%, NS). Although AERP was significantly decreased by SNS in both rats (each P < 0.01), increased heterogeneity of AERP by SNS was seen only in DM rats. PNS significantly decreased AERP and increased the incidence of AF (9 ± 5 to 30 ± 5% in control rats, 12 ± 6 to 27 ± 6% in DM rats, each P < 0.01) in both rats. The density of TH-positive nerves was heterogeneous in DM rats compared with control rats, whereas the heterogeneity of AChE-positive nerves was not different in the rats. The prevalence of AF was enhanced by adrenergic activation in diabetic hearts, in which heterogeneous sympathetic innervation was evident. These results suggest that neural remodeling may play a crucial role for increased AF vulnerability in DM.

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We hypothesized that similar samples of the same normal heart should report similar contractile index values. We analyzed anterior (AP) and posterior (PP) papillary muscles (PM) of the same heart (n = 46), whose representation of force fulfills this premise calculating force (F: mN), tension (T: mN/mm²), and tension per milligram of myocardium (δ: mN/mm²/mg). In all analyses, F and +dF/dt as well as T and dT/dt values were higher in heavier PM. These differences disappeared for δ and dδ/dt. There was a significant and positive correlation for F and T as well as its derivative with myocardial mass. Myocardial depression (verapamil) of PP, in comparison to AP, was not recognized by F or T, but was identified when reported as δ. We conclude that the normalization of tension for papillary muscle mass is the most appropriate form for reporting intrinsic contractile capacity in PM since F and T depend on the myocardial mass participating in contraction.

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In natural heart tissue, cell density is about 1.0 × 108/cm³, and the cell metabolism is very active. Therefore, culturing heart cells in 3-dimensions at high density and construction of engineered cardiac tissue in vitro is very difficult. The aim of this study was to simulate 3-dimensional culturing of cardiac cells and pursue a novel method to construct engineered cardiac tissue in vitro. The isolated neonatal rat ventricle cells were cultured at a high seeding density of 1 × 10⁶/cm². The cells at high density metabolized actively; the glucose consumption and lactic acid production of ventricle cells were much greater than those of fibroblasts cultured at the same density. The pH value of the culture medium of ventricle cells consistently decreased more rapidly. These cultured ventricle cells contained vascular endothelial cells, cardiomyocytes, and smooth muscle cells that appeared close to each other, and had overlapping nuclei and plenty of extracellular collagen. The cells at high density were treated with 0.2% trypsin to construct engineered cardiac cell sheets without scaffold. The engineered cardiac cell sheets could beat and roll up spontaneously, each sheet was 3 to 5 cells thick, and contained abundant cardiomyocytes and extracellular collagen.
In conclusion, cells cultured at high-density in vitro grew well in a 2-dimensional culturing environment, formed “quasi 3-dimension” culturing, and engineered cardiac cell sheets comprised of several layers of cells were constructed. This study provides some guidance for cardiac tissue engineering and a novel method to construct engineered cardiac tissue without scaffold.

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We report a case of simultaneous right and left coronary occlusion during percutaneous coronary intervention in the right coronary artery. An aortocoronary dissection induced by the forceful manipulation extended from the right to left sinus of Valsalva and occluded the ostia of both coronary arteries. The patient suffered cardiogenic shock and ventricular fibrillation. However, after successful rapid stenting to right and left coronary arteries, safe discharge was possible.

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We describe a thought-provoking case of Brugada syndrome in which a relationship between the diurnal electrocardiogram (ECG) changes and sex hormone levels was observed. A 36-year-old man who experienced cardiac arrest was referred to our hospital. He had a family history of sudden cardiac death. The 12-lead ECG exhibited a mild coved type ST-segment elevation in leads V1 and V2, which was enhanced by intravenous pilsicainide injection. Hence, this case was diagnosed as Brugada syndrome. The circadian rhythm of the serum testosterone level revealed low levels in the daytime (1.66-1.99 ng/mL) and high levels (2.52-3.42 ng/mL) in the nighttime. Interestingly, augmentation of the ST segment elevation and widening of the P wave were observed at around 2:00 AM, when the serum testosterone was recorded at its highest. Our report discusses the influence of the circadian rhythms of sex hormones on the ECG changes in Brugada syndrome.

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A 64-year-old man who had been prescribed antihypertensive drugs since 1971 attended our clinic in 1988 with hypertension and electrocardiographic abnormalities. An electrocardiogram revealed left axis deviation (LAD) in 1988 and slightly prolonged PQ intervals in 1993. Complete left bundle branch block (CLBBB) with LAD developed in May 1995. The wide QRS of the CLBBB had never returned to the normal narrow QRS and had intermittently alternated between LAD and normal axis. The PQ intervals were longer when the QRS axis showed LAD compared to that with normal QRS axis. The QRS complexes in leads V1-V3 revealed an R wave at LAD and a QS pattern at normal axis. During a deep breathing test, the QRS axis switched from normal axis to LAD at the end of forced expiration and also switched from normal axis to LAD within a few minutes after the exercise test. These results suggest that the shift of the QRS axis might be related to the tone of the autonomic nervous system.

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A 55-year-old male patient with a 10 year history of hemodialysis was admitted for examination of pericardial effusion. Specific echocardiography, MRI, and cardiac catheterization findings strongly suggested a diagnosis of effusive constrictive pericarditis. Pericardiectomy showed the following distinct findings. Two layers of fibrous tissue below the thickened pericardium emerged. The cardiac constriction had not been relieved until the inner layer was partially resected. We conclude that patients in dialysis associated constrictive pericarditis should undergo pericardiectomy before the adhesion between fibrous tissues becomes hard.

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