Chronic kidney disease and long-term outcomes of myocardial infarction.

BACKGROUND: Although chronic kidney disease (CKD) is a risk factor for cardiovascular disease, information about myocardial infarction (MI) with CKD is limited in the acute revascularization era. METHODS: To clarify the relationship between CKD and long-term outcomes of MI, consecutive 4550 patients with acute MI treated at 17 participating hospitals were analyzed. The primary study outcome was death from any cause, and a secondary endpoint was the first appearance major adverse cardiovascular events. RESULTS: Acute revascularization therapies were performed in 75.2% of the patients and the mean left ventricular ejection fraction (LVEF) was 53%. The median follow-up was 4.1 years (follow-up rate, 95.2%). Patients were divided into four categories (<45.0, 45.0 to 59.9, 60.0 to 74.9, and ≥ 75.0 mL/min per 1.73 m(2) of body-surface area) according to the glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease equation. A total of 1941 (42.7%) patients had an estimated GFR of <60.0 mL/min per 1.73 m(2). Mortality rates increased with declining estimated GFR. Unadjusted hazard ratios for total and cardiovascular death in the group with an estimated GFR of 45.0 to 59.9 mL/min per 1.73 m(2) using the group with an estimated GFR of ≥ 75.0 mL/min per 1.73 m(2) as the reference were 1.63 (95% CI, 1.28 to 2.07) and 2.09 (95% CI, 1.45 to 3.01), respectively. CONCLUSIONS: Even early-stage CKD should be considered a powerful risk factor for long-term cardiovascular death after acute MI with preserved LVEF in the acute revascularization era.

Effect of amlodipine + candesartan on cardiovascular events in hypertensive patients with coronary artery disease (from The Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease [HIJ-CREATE] Study).

Combination therapy with calcium channel blockers and angiotensin II receptor blockers is recommended as one of the effective therapies for hypertension. However, it remains unclear whether this combination reduces major adverse cardiovascular events (MACEs) in patients with hypertension with coronary artery disease (CAD). The purpose of the present study was to examine the effects of amlodipine plus candesartan on MACEs in patients with hypertension with CAD. The study population was drawn from The Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE), which was a multicenter, prospective, randomized controlled trial including 2,049 patients with hypertension with angiographically documented CAD. Subgroup analysis was performed in patients treated with amlodipine at baseline (n = 388). The median follow-up period was 4.3 years. Treatment using amlodipine plus candesartan reduced the risk for MACEs by 39% (p = 0.015) compared to that using amlodipine without angiotensin II receptor blockers. Among the individual events constituting MACEs, the incidence of unstable angina pectoris requiring hospitalization was significantly lower, by 52% (p = 0.007). In conclusion, amlodipine plus candesartan demonstrated a more favorable effect on reducing cardiovascular events in patients with hypertension with CAD compared to amlodipine-based therapy without candesartan.

Acute decompensated heart failure syndromes (ATTEND) registry. A prospective observational multicenter cohort study: rationale, design, and preliminary data.

Acute heart failure syndromes (AHFS) are likely to increase in the future, and the high readmission rate of patients with AHFS is an important issue in Western countries. However, there are very few published epidemiological studies on AHFS in the Asia Pacific region. Because AHFS are heterogeneous, the characteristics, clinical profile, and management of AHFS should be clarified in an epidemiological study. The acute decompensated heart failure syndromes (ATTEND) registry is a prospective, observational, multicenter cohort study being performed in Japan and is the first epidemiological study of AHFS in the Asia Pacific region. This study is designed to investigate several aspects of AHFS as follows: (1) the registry allows patient-based data collection for precise evaluation of patient characteristics and short-term outcomes, including the readmission rate; (2) confirmation of clinical assessments can be performed, and new clinical assessments can be created; and (3) feedback allows the modification of guidelines for clinical management. The present report describes the clinical characteristics of patients with AHFS in Japan based on the preliminary data collected in this study, and the similarities and differences in characteristics of these patients compared with those in Western countries. Although most of the patient characteristics did not differ from those reported in Western studies, there are some unique findings in this study, including a high rate of treatment with carperitide (69.4%) and angiotensin II receptor blockers (53.9%) at discharge and a longer hospital stay (median 21 days). The ATTEND registry is designed to provide valuable information to clarify the characteristics of patients with AHFS to improve their management.

Acute efficacy and safety of intravenous administration of nicorandil in patients with acute heart failure syndromes: usefulness of noninvasive echocardiographic hemodynamic evaluation.

This study was conducted to evaluate the acute efficacy and safety of intravenous administration of nicorandil in patients with acute heart failure syndromes (AHFS), under noninvasive hemodynamic assessment with transthoracic Doppler echocardiography. After baseline hemodynamic measurements, initial bolus and 48-hour continuous intravenous nicorandil infusion were begun in 14 hospitalized patients with AHFS. After 2-hour infusion, estimated pulmonary capillary wedge pressure was reduced from 21.4 +/- 6.4 to 17.5 +/- 5.2 mm Hg (P < 0.05) and was sustained for 48 hours to 16.2 +/- 5.5 mm Hg (P < 0.05). A significant increase in estimated cardiac output was observed at 2 hours, from 4.0 +/- 1.0 to 4.8 +/- 1.3 L/min (P < 0.05). This increase was sustained for 48 hours to 5.8 +/- 1.8 L/min (P < 0.05). The high blood pressure (BP) group (baseline systolic BP > or = 140 mm Hg, n = 7) exhibited significant decrease in systolic BP (from 156.7 +/- 14.2 to 135.4 +/- 13.3 mm Hg, P < 0.05). In contrast, there was no change in systolic BP in the low BP group (baseline systolic BP < 140 mm Hg, n = 7) over 48 hours (from 107.6 +/- 20.4 to 107.7 +/- 17.4 mm Hg, P = not significant). The results of this study demonstrate the acute hemodynamic efficacy and safety of intravenous administration of nicorandil and also suggest the usefulness of noninvasive echocardiographic hemodynamic evaluation in the urgent phase of AHFS.

Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE).

AIMS: To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension. METHODS AND RESULTS: Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based (n= 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors (n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76-1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66-1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66-1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59-1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16-0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001). CONCLUSION: Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

Serum creatinine on admission predicts long-term mortality in acute myocardial infarction patients undergoing successful primary angioplasty: data from the Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) Registry.

BACKGROUND: Data about the long-term mortality of acute myocardial infarction (AMI) patients with renal insufficiency who received sufficient early revascularization are scant, so the present study evaluated the impact of serum creatinine levels on the long-term mortality in patients with AMI undergoing successful primary percutaneous coronary intervention (PCI). METHODS AND RESULTS: The Heart Institute of Japan Acute Myocardial Infarction (HIJAMI) registry has 3,021 consecutive AMI patients. Primary PCI was attempted in 1,451 patients and successful revascularization was obtained in 1,359 patients (93.6%). An elevated serum creatinine level, defined as creatinine > or =1.2 mg/dl, was observed in 216 patients (15.8%). Univariate analyses showed statistical differences between normal and elevated serum creatinine groups in age, gender, hypertension, previous myocardial infarction, number of diseased vessels and Killip class. During a median follow-up period of 39 [32-49] months, the event-free survival rate was lower in elevated creatinine group than normal creatinine group. Multivariate Cox proportional hazards model showed that serum creatinine level was an independent predictor of long-term mortality (adjusted hazard ratio 1.43 [95% confidence interval 1.03-1.99]). CONCLUSION: The serum creatinine level on admission in patients with AMI predicts long-term mortality, even in those with successful primary PCI.

Effect of early statin treatment at standard doses on long-term clinical outcomes in patients with acute myocardial infarction (the Heart Institute of Japan, Department of Cardiology Statin Evaluation Program).

Long-term preventive effects of standard statin therapy in patients with acute myocardial infarction (AMI) against a secondary cardiac event remain unclear. The aims of this study were to evaluate and clarify characteristics of patients with AMI in whom standard statin therapy has beneficial effects against a secondary event in a real-world setting. Between 1999 and 2004, 4,075 patients with AMI were registered and followed prospectively, of whom 1,404 (matched by propensity scores) were analyzed. Statin use was defined as prescription on discharge from the hospital, and the control group was not prescribed statins at discharge. The primary end point was total mortality rate. Final follow-up was performed in June 2006 (median 4.1 years), and follow-up rate was 97.2%. During follow-up, 139 patients died, including 87 (12.4%) from the control group and 52 (7.4%) from the statin group. The hazard ratio for statin therapy was 0.64 (95% confidence interval 0.45 to 0.90, p = 0.011) throughout the study. Early statin therapy was strongly correlated with a lower risk of cardiovascular death, less recurrence of AMI, and less heart failure. Statin therapy was particularly beneficial for men, patients > or =60 years of age, and patients with a high low-density lipoprotein cholesterol level > or =155 mg/dl. In conclusion, these findings suggest that initiating standard rather than intensive statin therapy immediately after AMI decreases long-term mortality and subsequent cardiac events.

[Clinical impact of nephropathy induced by contrast medium in patients with acute myocardial infarction undergoing emergent coronary angiography].

OBJECTIVES: The incidence of contrast-induced nephropathy (CIN) after coronary angiography and the prognostic value in patients with acute myocardial infarction remains to be determined. This study investigated the frequency, predictors of CIN, and the prognostic significance of CIN in acute myocardial infarction patients undergoing emergent coronary angiography. METHODS: This study included 132 consecutive acute myocardial infarction patients undergoing emergent coronary angiography within 24 hr after the onset between January 1999 and June 2001. The serum creatinine concentration was measured on admission and at 48 hr after contrast medium exposure. CIN was defined as an increase in serum creatinine from the baseline > or = 0.5 mg/dl or > or = 25% at 48 hr after emergent coronary angiography. The patient characteristics, and in-hospital and long-term mortality were compared between the CIN and non-CIN groups. RESULTS: CIN occurred in 15 patients (11.4%) after emergent coronary angiography. The predictor of CIN development was preexisting renal impairment (serum creatinine concentration > or = 1.2 mg/dl on presentation; 21.9% vs 8.0%, odds ratio 3.22, 95% confidence interval 1.07-9.74, p = 0.04). In-hospital mortality was significantly higher in the CIN group than in the non-CIN group (13.3% vs 1.7%; odds ratio 8.85, 95% confidence interval 1.15-68.2, p = 0.01). The long-term mortality (mean follow-up period of 40 months) was also higher in the CIN group (26.7% vs 8.6%; hazard ratio 3.91, 95% confidence interval 1.21-12.5, p = 0.02). CONCLUSIONS: CIN was an independent predictor of both in-hospital and long-term mortality in acute myocardial infarction patients undergoing emergent coronary angiography. Preexisting renal insufficiency was associated with subsequent CIN.

A large-scale prospective cohort study on the current status of therapeutic modalities for acute myocardial infarction in Japan: rationale and initial results of the HIJAMI Registry.

BACKGROUND: In Western countries, several multicenter collaborative studies on acute myocardial infarction (AMI) have provided much information about this disease. In Japan, on the other hand, there have been few cohort studies in which a sufficient number of Japanese patients with AMI were registered during a short period. This fact explains the absence of a database from which strategies for treating Japanese patients with AMI could be established. The purpose of this study was to build a comprehensive database on Japanese patients with AMI to elucidate their characteristics. METHODS: Between January 1999 and June 2001, we consecutively registered all patients with AMI who were admitted to 17 participating medical institutions, including The Heart Institute of Japan, Cardiology (HIJC), Tokyo Women's Medical University. A standardized case report form was used to register all the patients. RESULTS: A total of 3,021 consecutive patients was registered (2,136 men, 70.7%; 885 women, 29.3%) with a median age of 69 years [59, 77]. Among the patients, there were 851 elderly individuals (28.2%) > or = 76 years and 1102 patients with diabetes (36.5%). On index electrocardiogram, ST-elevation myocardial infarction was observed in 2,392 patients (79.2%). Within 24 hours after the onset of AMI, coronary angiography was conducted for 2,177 patients (72.1%). Primary percutaneous coronary intervention and coronary thrombolysis were conducted for 1,755 (58.1%) and 491 patients (16.3%), respectively, and percutaneous coronary intervention or coronary artery bypass grafting was additionally carried out in 303 patients. By the time of discharge, coronary angiography and coronary artery bypass grafting were performed in 2,659 (88.0%) and 137 patients (4.5%), respectively. During initial hospitalization, 285 patients died and the overall inhospital mortality rate was 9.4%. During hospitalization, cardiogenic shock and cardiac rupture were observed in 6.1% and 2.8% of the patients, respectively. The inhospital mortality rate is still high in patients with AMI with such mechanical complications and in elderly patients. CONCLUSION: In our prospective cohort, we showed that Japanese patients with AMI could be characterized as (1) having a disease severity comparable with values observed in Western populations and (2) receiving early reperfusion therapy by PCI, which was used widely and safely, but nevertheless (3) exhibiting a high inhospital mortality rate. Our data indicate that further improvements in therapy for AMI in elderly patients and for AMI with mechanical complications are essential in Japan.

Reperfusion phenomenon is a strong predictor of left ventricular remodeling after acute myocardial infarction.

BACKGROUND: Many clinicians have seen the reperfusion phenomenon, a paradoxical response that includes a transient increase of chest pain, additional ST-segment elevation or ventricular arrhythmias immediately after coronary reperfusion, in patients with acute myocardial infarction (AMI). The aim of the present study was to investigate the impact of this phenomenon during coronary reperfusion on left ventricular (LV) remodeling in patients with AMI. METHODS AND RESULTS: One hundred and thirty-eight consecutive patients with a first anterior-wall AMI, undergoing coronary reperfusion treatment within 24 h of onset were prospectively evaluated for reperfusion phenomenon and followed up with scheduled evaluations of LV function and morphology with left ventriculography for 1 year. Of the 138 enrolled patients, 77 underwent serial left ventriculography at the acute, subacute and 1-year phases. Of these 77 patients, 39 demonstrated the reperfusion phenomenon. The LV end-diastolic volume index significantly increased from the acute to subacute phase and to the 1-year phase, but was unchanged in the 38 patients without reperfusion phenomenon. In multivariate analysis, reperfusion phenomenon was the only determinant of LV dilatation after AMI. CONCLUSIONS: Reperfusion phenomenon was a strong predictor of LV remodeling after reperfusion therapy for AMI.

[Biventricular pacing dramatically improved critical heart failure in idiopathic dilated cardiomyopathy: two case reports].

Two cases of dilated cardiomyopathy with intraventricular conduction delay, or left bundle-branch block and refractory heart failure, were markedly improved by biventricular pacing. The first patient's condition (Case 1) could not be improved despite administration of intravenous inotropic agents. He required mechanical ventilation and continuous hemodialysis as his condition worsened. Biventricular pacing was performed which was soon followed by increased blood pressure and decreased mitral regurgitation. As a result, mechanical ventilation, continuous hemodialysis and intravenous medication could be withdrawn. The second patient's condition (Case 2) deteriorated because of bradycardia due to advanced atrioventricular block. Unexpectedly, temporary right atrium-right ventricle sequential pacing increased mitral regurgitation and then caused heart failure, requiring a higher dose of inotropic and diuretic agents. Therefore, biventricular pacing was performed which rapidly improved both his symptoms and hemodynamic state, allowing reduction of the medication dose. Biventricular pacing dramatically improves critical conditions in patients in life-threatening states.

Marked improvement of left ventricular function after parathyroidectomy in a hemodialysis patient with secondary hyperparathyroidism and left ventricular dysfunction.

A 52-year-old woman, a hemodialysis patient, was admitted because of exertional dyspnea. Echocardiography showed left ventricular (LV) dilatation and reduced contraction. Coronary angiography showed no fixed stenosis. She had elevated levels of parathyroid hormone (PTH) as a result of secondary hyperparathyroidism with advanced renal failure. After parathyroidectomy, marked improvement of LV function following immediate decrease of blood levels of PTH was observed. It is suggested that PTH might have a significant role in the pathogenesis of LV dysfunction and that parathyroidectomy might be effective as a therapy for heart failure in some patients with secondary hyperparathyroidism and LV dysfunction.