Epidemiological studies have demonstrated an association between low serum albumin levels and coronary heart disease and mortality. Nevertheless, the impact of a low serum albumin level during acute coronary syndrome has not yet been established. The aim of the present study was to investigate whether low serum albumin levels are associated with adverse outcomes in acute coronary syndrome. We enrolled 82 consecutive patients with acute coronary syndrome from whom venous blood for serum albumin measurement was drawn immediately upon hospital admission. Thirty-five patients had a low albumin level (hypoalbuminemia) and 47 had a normal albumin level (normoalbuminemia). In-hospital adverse outcomes (death, acute heart failure, cardiogenic shock, and reinfarction) were recorded during hospitalization in the intensive coronary care unit. The results of our study showed that the incidence of in-hospital adverse outcomes was 43%, with death occurring in 8 patients (10%). In-hospital adverse outcomes occurred more frequently in patients presenting with hypoalbuminemia, whereas mortality did not differ significantly. Univariate analysis showed that hypoalbuminemia was associated with a 2.8-fold greater risk of developing adverse outcomes. This risk was greater in the subgroup of NSTEACS (5.4-fold increased risk), but not in those with STEMI. Adjustment with other covariates revealed that hypoalbuminemia did not predict independently in-hospital adverse outcomes. It interacted with other predictors, especially Killip class II-IV, which was consistently an independent predictor of in-hospital adverse outcomes.
Recently, several studies have showed that bare metal stent (BMS) restenosis is not a benign clinical entity. However, clinical presentation of BMS restenosis in Japanese patients has not been fully evaluated. Follow-up coronary angiography after BMS implantation was performed in 473 patients with 523 lesions. Of these, BMS restenosis was observed in 167 lesions (31.9%). Clinical presentation of BMS restenosis was classified into 4 categories: 1) acute myocardial in-farction, 2) unstable angina, 3) stable angina, and 4) no symptom. Acute myocardial infarction (0%) and unstable angina (3.8%) were infrequent clinical presentations in patients with BMS restenosis compared to stable angina (26.9%) and no symptom (69.2%). BMS restenosis may be a benign clinical entity in Japanese patients.
Cobalt chromium stents (CCS) are seldom compared to drug-eluting stents (DES) for coronary intervention in published clinical trials. We evaluated the daily usage patterns of CCS in comparison to DES unconstrained by eligibility criteria. We compared consecutive patients (n = 303) with de novo lesions treated exclusively with a CCS to 432 patients treated exclusively with a DES. Patients in the CCS group were older, frequently had heart failure, renal failure, prior coronary balloon angioplasty, prior stroke, more comorbidities, and more multivessel disease than the DES group. The DES group had longer and more type C and left anterior descending (LAD) coronary artery lesions. The in-hospital major adverse cardiac events (MACE; death, myocardial infarction, stroke and target lesion revascularization (TLR)) were similar. At 6 months, the cumulative rate of MACE was 12.9% in the CCS group and 5.6% in the DES group (P < 0.001), and this was driven by TLR. The rates of stent thrombosis were similar in CCS (0.9%) and DES (1.0%) patients. In conclusion, the CCS were used in clinically higher risk patients, while DES were used in more severely diseased coronary arteries. Drug-eluting stent use resulted in lower rates of clinically driven repeat revascularization with similar rates of death, MI, stroke, and stent thrombosis.
Tai Chi is a traditional Chinese conditioning exercise that has been used to integrate slow movements, controlled breathing, and mental concentration. The aim of the study was to determine whether Tai Chi training in addition to cardiac rehabilitation would result in a shift toward increased vagal activity of autonomic markers, such as baroreflex sensitivity (BRS) and heart rate variability (HRV). Twenty patients with coronary heart disease (CHD) (male/female: 13/7, mean age: 67.8 ± 4.2 years, mean interval time after a coronary event: 19.8 months) completed this study. The Tai Chi group (n = 10) practiced supervised Tai Chi training once a week and home-based Tai Chi training three times a week together with conventional cardiac rehabilitation for one-year. The control group (n = 10) conducted the conventional cardiac rehabilitation only. BRS and HRV were evaluated at the baseline and after one-year of Tai Chi training. Compared with the controls, patients in the Tai Chi group showed statistically significant improvement in BRS (P = 0.036). These associations persisted after adjustment for age and other covariates. On the other hand, there were no significant trends seen in HRV. Additional Tai Chi training during cardiac rehabilitation may augment reflex vagal regulation, which adds importantly to knowledge of cardiac rehabilitation on autonomic regulation and clinical management of CHD.
The aim of the present study was to determine whether symptoms of atrial fibrillation (AF) differ between patients with and without subsequent permanent AF. Sixty-four patients (68 ± 10 years old, 45 males) were recruited. AF follow-up was started at the age of 61 ± 10 years and accomplished in a median period of 4.9 years (396 person-years). Permanent AF, defined as lasting > 180 days, developed in 17 patients (14 males) (43 per 1000 person-years). The AF follow-up period was longer in the permanent AF group than in the non-permanent AF group (median, 9.8 versus 4.2 years, P < 0.001). For baseline characteristics, hypertension was less frequent in the permanent AF group than in the nonpermanent AF group (18% versus 45%, P < 0.05). A retrospective questionnaire survey regarding initial AF symptoms was conducted. The severity of AF symptoms by a 4-grade scale was significantly milder in the permanent AF group than in the nonpermanent AF group (P < 0.05). Cox proportional hazards model analysis revealed that the severity of initial AF symptoms was related to the subsequent development of permanent AF (hazard ratio 0.46 per grade, 95% confidence interval 0.23 - 0.93, P < 0.05), but age, gender, hypertension, diabetes mellitus, organic heart disease, and left atrial dimension were not. The permanent AF-free rate was significantly lower in 33 patients with mild symptoms than in 31 patients with severe symptoms (log-rank test, P < 0.05). These results point to an inconspicuous feature in the development of permanent AF.
The mortality of heart failure patients with renal insufficiency is high, and these patients tend to develop diuretic resistance. Under these conditions, continuous hemodiafiltration (CHDF) is a possible alternative volume reduction therapy to diuretics. However, its efficacy and safety are not clear. Between April 2005 and March 2008, 248 patients with acute decompensated heart failure were admitted to the CCU of Kyoto City Hospital. Of those patients, 31 (20 volume overloaded heart failure, 11 cardiogenic shock) received CHDF therapy, and their weight loss, acute hemodynamic changes, and clinical outcome were assessed to evaluate the efficacy and safety of CHDF therapy. CHDF was performed for 6.5 ± 6.5 days. There was no significant change in acute hemodynamics after CHDF initiation. In the volume overloaded heart failure (VH) group, significant weight loss was observed at 24 hours and 48 hours after CHDF initiation (P < 0.001). In-hospital mortality of the VH group and cardiogenic shock (CS) group were 10.0% and 54.5%, respectively. CHDF for acute decompensated heart failure (ADHF) is a safe, effective, and reliable volume reduction therapy for volume overloaded heart failure. Further investigation is required to assess the effectiveness of CHDF for cardiogenic shock.
Combined treatment with an angiotensin II receptor blocker and hydrochlorothiazide (HCT) is advocated to control hypertension (HT). Hepatocyte growth factor (HGF) may be a new marker to evaluate endothelial dysfunction (ED), which is a potential target in treating HT. The aim of the present study was to compare the effects of Telmisartan/HCT with Losartan/HCT on serum HGF and ED in hypertensive patients. Hypertensive patients were randomly divided into a Telmisartan/HCT (group T) or Losartan/HCT group (group L) and received one tablet of either drug per day for 8 weeks. Serum HGF, nitric oxide (NO), plasma von Willebrand factor (vWF), and endothelin (ET) were measured before treatment and after 8 weeks of treatment. Twenty healthy subjects were selected as controls (control group). HGF, vWF, ET, and the ET/NO ratio were higher, and NO was lower in hypertensive patients than those in the control group (all P < 0.01). After treatment for 8 weeks, HGF, vWF and ET decreased, and NO increased significantly in both groups (all P < 0.01). The reductions in BP and HGF and increase in NO (ΔNO) were not significantly different between the two groups (all P > 0.05), but the reductions in vWF and ET (ΔET) and ΔET/ΔNO ratio were more obvious in group T than in group L (all P < 0.01). There was no significant correlation between the changes in most of the measured parameters and the extent of BP reduction in either group. Both Telmisartan/HCT and Losartan/HCT could decrease serum HGF and improve ED, which was independent of the antihypertensive effects. However, the improvement in ED may be superior with Telmisartan/HCT than Losartan/HCT when the BP-lowering effects are the same.
The aim of the present study was to investigate the relationship between rejections and gene expression of Ca2+-handling proteins in heart transplant recipients. Thirty-seven heart transplant recipients underwent routine endomyocardial biopsy. Levels of sarcoplasmic reticulum Ca2+-ATPase (SERCA2) and ryanodine receptor-2 mRNAs in endomyocardial tissue were quantified by a real-time quantitative reverse transcription polymerase chain reaction (RT-PCR) method. Rejections were diagnosed according to the conventional International Society for Heart and Lung Transplantation criteria. Patients were classified as follows; group AR+ (n = 9) with rejection grade of 2 or higher versus group AR- (n = 28) with rejection grade of 0, 1a or 1b at the time of biopsy, and group Rec-AR+ (n = 6) with a history of more than 4 episodes of treatment required rejection versus group Rec-AR- (n = 31) without history of recurrent rejection. The mRNA levels of the SERCA2/GAPDH ratio and ryanodine receptor-2/GAPDH ratio were not different between group AR+ and group AR-; however, they were reduced in group Rec-AR+ more than in group Rec-AR- (0.83 ± 0.07 versus 0.90 ± 0.07, P = 0.034, 0.74 ± 0.06 versus 0.84 ± 0.10, P = 0.027, respectively). A single episode of on-going rejection would not affect myocardial Ca2+-handling proteins; however, cumulative rejection episodes might alter the gene expression of myocardial Ca2+-handling proteins in heart transplant recipients.
The number of heart transplant (HTx) surgeries in Japan is expected to increase under the Revised Organ Transplant Law. To date, among 69 HTx surgeries performed in Japan, 27 operations (39.1%) were performed at our institution, the National Cardiovascular Center (NCVC), located in Osaka. We have reviewed the outcomes of HTx conducted at NCVC during a 10 year period (May 1999 to January 2009). Among 27 heart transplant recipients at NCVC, the clinical charts of 26 recipients whose post-HTx period exceeded 1 year were retrospectively reviewed and compared to data from the International Society for Heart and Lung Transplantation (ISHLT) Registry. The survival rate of our recipients was 96.2% at 10.8 years, which was excellent even compared to the ISHLT Registry. The immunosuppressive regimen at NCVC was equivalent to that of the ISHLT Registry, except for more frequent use of Muromonab-CD3 (26.9% versus 3.3%, P < 0.0001) and an initial CSA-based regimen (65.3% versus 34.4%, P < 0.001). The drug we use for induction therapy has been recently changed from Muromonab-CD3 to Basiliximab. The incidences of post-HTx hypertension, diabetes, hyperlipidemia, and renal insufficiency were significantly less in patients at NCVC compared to those in the ISHLT Registry, however, the incidence of transplant coronary artery disease (TxCAD) was almost identical. Clinical review of post-HTx outcome at NCVC can provide useful information for Japanese transplant cardiologists who will engage in HTx management.
Recently, platelet-derived growth factor (PDGF) has been implicated in the abnormal proliferation and migration of pulmonary artery vascular smooth muscle cells. Imatinib meslylate, a PDGF receptor antagonist, has been reported to dramatically improve pulmonary arterial hypertension (PAH) in some human cases as well as animal models. Five patients with PAH (3 scleroderma-associated PAH and 2 idiopathic/familial PAH) taking no less than 2 PAH agents were treated with low-dose imatinib (100 mg/day) for 24 weeks. Imatinib was titrated up to 200 mg/day unless major complications were observed. Before and after the treatment, right heart catheterization, cardiopulmonary exercise test, respiratory function test, and plasma concentration measurements of PDGF-BB and vascular endothelial growth factor (VEGF) were performed. Plasma PDGF-BB levels were significantly decreased after 12 weeks of treatment (P = 0.04), while VEGF did not change. Although 24 week administration of imatinib did not show a significant effect on hemodynamics and exercise capacity, 2 patients with high plasma PDGF-BB levels showed a good initial response of more than a 15% decrease in pulmonary vascular resistance. Diffusion capacity of the lung for carbon monoxide significantly improved after 12 weeks of treatment (P < 0.01) and this improvement tended to be sustained for 24 weeks (P = 0.05). Renal dysfunction was observed in 3 patients during imatinib therapy. The upregulated PDGF-BB in patients with PAH could be suppressed by imatinib treatment, and also seemed to be one of the determinant factors for its efficacy.
MEKK1 is a ubiquitously expressed mitogen activated protein kinase that is involved in tissue remodeling in a variety of settings including carotid artery blood flow cessation, wound healing, and breast adenocarcinoma intravasation. Here, we have tested the function of MEKK1 in genetic hypertrophic cardiomyopathy (HCM). MEKK1 was genetically deleted in C57Bl6/J mice expressing a mutant α-myosin heavy chain (HCM-MEKK1-/-). The absence of MEKK1 in HCM resulted in a more pronounced hypertrophy when compared to HCM mice with the MEKK1 gene intact without further increases in atrial natriuretic factor and β-myosin heavy chain (MyHC) expression and fibrosis. Since MEKK1 is required for the induction of several tissue proteases, we tested the hypothesis that cardiac enlargement of HCM- MEKK1-/- mice was due to altered expression of urokinase-type plasminogen activator (uPA), JunB, matrix-metalloproteinase (MMP), and tissue inhibitors of MMPs (TIMPs). Because of its role in preventing apoptosis, we also tested the loss of MEKK1 on apoptotic mediators Bcl-2, cytochrome C, caspase-9, and caspase-3. uPA expression was decreased while JunB, MMP-9, caspase-9, and caspase-3 activities were elevated in HCM- MEKK1-/- hearts when compared to MEKK1-/-, wild-type (WT), and HCM mice. Bcl-2 and Cyt C expression was elevated only in HCM mice. We conclude that the absence of MEKK1 induces a more pronounced cardiac hypertrophy to HCM through altered expression of proteases implicated in cardiac remodeling and increased apoptosis.
QT prolongation may increase the risk of torsades de pointes (TdP). Early afterdepolarizations (EADs) and transmural dispersion of repolarization have been known to serve as physiological substrates and predictors for TdP. Abnormal Ca2+ cycling is the proximate cause of EADs, and Ca2+ cycling is abnormal in heart failure (HF). However, the mechanisms for drug-induced TdP in HF are poorly understood. The purpose of this study was to search for torsadogenic-modifying effects of verapamil, ryanodine, KB-R7943, W-7, KN-93, and H-8 on ventricular premature depolarizations (VPD) and TdP in rabbits with HF. Rabbits with HF were pretreated with propranolol followed by test articles before continuous infusion of dofetilide to induce TdP. In the control hearts, VPD and TdP were induced in all rabbits and the onsets of VPD and TdP were 3.6 ± 1.3 minutes and 10.3 ± 1.4 minutes, respectively. Dofetilide lengthened RR, QT and QTc. Verapamil, ryanodine and H-8 significantly delayed onset of VPD (P < 0.05) and suppressed TdP (P < 0.01). KB-R7943, W-7, and KN-93 accelerated onset of TdP. Blockades of L-type Ca2+ channel, ryanodine channel, and protein kinase A prevent dofetilide-induced TdP, suggesting roles for intracellular Ca2+ overload and Ca2+ signaling pathways in drug-induced TdP.
Culprit lesions of acute coronary syndrome (ACS) were observed by intravascular optical coherence tomography (OCT). OCT images revealed diffuse intimal thickening, reduced lumen area with vascular contraction, and thrombus formation. No OCT images of atherosclerotic plaque disruption were found. Vascular contraction disappeared and the lumen was dilated after intracoronary injection of nitroglycerin. The main mechanism of ACS in this case was therefore considered to be coronary vasospasm. OCT may be useful for evaluating the mechanism of ACS.
A 48 year-old obese male with hypertension was admitted to our department because of severe right-dominant heart failure. His heart rhythm was 2:1 atrial flutter and the left ventricle was diffusely hypertrophic and hypokinetic. Primary aldosteronism was diagnosed based on severe hypokalemia (2.6 mEq/L) and a low renin-high aldosterone state with hypertension despite the use of an angiotensin-II receptor blocker, but its etiology could not be clarified with computed tomography, adrenal scintigraphy, and adrenal vein sampling. Ascites and edema rapidly worsened. Ascites aspiration was performed daily, until serum potassium was normalized by a full dose of an aldosterone receptor blocker (spironolactone 100 mg/day). A diuretic (furosemide) was then added. Rate control of atrial flutter was obtained with a beta-adrenergic blocker, and anticoagulation therapy was started. His heart failure was successfully controlled. Coronary arteries were normal on coronary arteriograms, and an endomyocardial biopsy sample obtained from the left ventricle did not show any specific pathological findings. Blood pressure was well controlled with the full dose of the aldosterone receptor blocker, but he died one year later due to intracerebral hemorrhage. As his heart failure was right dominant, we believe that its etiology may have been hyperaldosteronism-induced cardiomyopathy, and not advanced hypertensive heart disease.