Hideo Mitamura

C-Reactive Protein as a Predictor of Infarct Expansion and Cardiac Rupture After a First Q-Wave Acute Myocardial Infarction

BACKGROUND Pump failure after acute myocardial infarction (AMI) can be predicted by several indices that estimate infarct size. However, there are few indices that predict infarct expansion and cardiac rupture. We focused on the prognostic significance of serum C-reactive protein (CRP) after AMI. METHODS AND RESULTS Serum CRP levels were measured every 24 hours in 220 patients with a first Q-wave AMI. In-hospital complications, predischarge left ventriculographic findings, and long-term prognosis were assessed in relation to peak CRP levels. Peak levels of both CRP and creatine kinase (CK) were higher in patients with pump failure than in those without pump failure. In patients with cardiac rupture, peak CRP levels were higher than in those without rupture (P=.001); peak CK levels were not predictive. Higher CRP levels were found in patients with left ventricular aneurysm (P=.001 versus those without), aggravated heart failure (P=.03 versus those without), and cardiac death (P<.0001 versus survivors) during the first year after AMI. Multivariate analysis confirmed that an elevation of the peak CRP level > or = 20 mg/dL was an independent predictor of cardiac rupture (relative risk, 4.72; P=.004), left ventricular aneurysmal formation (relative risk, 2.11; P=.03), and 1-year cardiac death (relative risk, 3.44; P<.0001). CONCLUSIONS Cardiac rupture, left ventricular aneurysmal formation, and 1-year cardiac death were associated with an elevation of serum CRP early after AMI, suggesting that elevation of CRP levels after AMI may predict infarct expansion.

Prognostic significance of peripheral monocytosis after reperfused acute myocardial infarction: A possible role for left ventricular remodeling

OBJECTIVES The aim of this study was to determine the significance of peripheral monocytosis in clinical outcome after reperfused acute myocardial infarction (AMI), especially relating to post-infarct left ventricular (LV) remodeling. BACKGROUND Peripheral monocytosis occurs two to three days after AMI, reflecting infiltration of monocytes and macrophages into the necrotic myocardium. However, the prognostic significance of peripheral monocytosis after AMI remains to be determined. METHODS A total of 149 patients with first Q-wave AMI were studied. White blood cell (WBC) count, percentage of monocytes and serum C-reactive protein level were measured every 24 h for four days after the onset of AMI. We assessed association between peripheral monocytosis and prognosis including pump failure, LV aneurysm and long-term outcome after AMI. RESULTS Patients with pump failure (p < 0.0001) or LV aneurysm (p = 0.005) had higher peak monocyte counts than those without these complications. Predischarge left ventriculography revealed that peak monocyte count was positively correlated with LV end-diastolic volume (p = 0.024) and negatively correlated with ejection fraction (p = 0.023). Multivariate analyses showed that peak monocyte count > or = 900/mm(3) was an independent determinant of pump failure (relative risk [RR] 9.83, p < 0.0001), LV aneurysm (RR 4.78, p = 0.046) and cardiac events (RR 6.30, p < 0.0001), including readmission for heart failure, recurrent myocardial infarction and cardiac deaths, including sudden deaths. CONCLUSIONS Peripheral monocytosis is associated with LV dysfunction and LV aneurysm, suggesting a possible role of monocytes in the development of LV remodeling after reperfused AMI.

Prevalence of atrial fibrillation in the general population of Japan: An analysis based on periodic health examination

BACKGROUND The mortality and morbidity rates of various cardiovascular diseases differ between Western countries and Japan. The age- and gender-specific prevalence rate of atrial fibrillation (AF) in the general population of Japan was determined using the data from periodic health examinations in 2003. METHODS Data of 630,138 subjects aged 40 years or more (47% were men and 34% were employees of companies and local governments) were collected from northern to southern Japan. The prevalence of diagnosed AF in each 10-year age group of both men and women was determined. Based on these prevalence rates and the Registry of Residents, the number of people having AF in Japan was estimated. RESULTS The prevalence rate of AF increased as both male and female subjects aged, and it was 4.4% for men but only 2.2% for women aged 80 years or more (p<0.0001). As a whole, the AF prevalence of men was three times that of women (1.35 versus 0.43%, p<0.0001). There may be approximately 716,000 people (95% confidence interval (CI), 711,000-720,000) with AF in Japan, an overall prevalence of 0.56%. The number of people having AF was projected to be 1.034 (95% CI, 1.029-1.039) million, an overall prevalence of 1.09%, in 2050. CONCLUSIONS The prevalence of AF increased in Japan as the population aged, as in Western countries. The overall prevalence of AF in Japan is approximately two-thirds of that in the USA. The projected increase in the number of people having AF is modest in Japan in 2050.

Autoantibodies against the second extracellular loop of beta1-adrenergic receptors predict ventricular tachycardia and sudden death in patients with idiopathic dilated cardiomyopathy

OBJECTIVES We sought to define the clinical and long-term prognostic implications of autoantibodies that act against the second extracellular loop of beta1-adrenergic receptors (ARs) in patients with idiopathic dilated cardiomyopathy (IDC). BACKGROUND Although autoantibodies directed against various domains of beta-ARs are found in patients with IDC, only a subgroup against the second extracellular domain of beta1-ARs exerts intrinsic sympathomimetic-like actions on human beta-ARs. It is suggested that the autoantibodies take part in the pathophysiology of IDC and may affect long-term prognosis of patients with this disorder. METHODS Sera from 104 patients with IDC were screened for autoantibodies that act against the second extracellular loop of beta1-ARs by enzyme-linked immunosorbent assay, using a synthetic peptide corresponding to the domain. Relations of the autoantibodies to clinical variables and long-term prognosis were assessed by multivariate analysis. RESULTS Autoantibodies were detected in 40 patients (38%). Multifocal ventricular premature contractions (p < 0.01) and ventricular tachycardia (VT; p < 0.01) were more common in autoantibody-positive than in autoantibody-negative patients, although no differences in cardiac function or neurohormonal levels were demonstrated. The presence of autoantibodies (p = 0.001) and a low left ventricular ejection fraction (LVEF <30%; p = 0.02) were independent predictors of VT. Sudden death was independently predicted by the presence of autoantibodies (p = 0.03), as well as by LVEF <30% (p = 0.01), whereas total mortality was predicted only by LVEF <30% (p = 0.001). CONCLUSIONS Autoantibodies directed against the second extracellular loop of beta1-ARs were closely related to serious ventricular arrhythmias in patients with IDC, and the presence of autoantibodies independently predicted sudden death. These autoantibodies may contribute to electrical instability in patients with IDC.

Preinfarction angina as a major predictor of left ventricular function and long-term prognosis after a first Q wave myocardial infarction

OBJECTIVES The purpose of this study was to assess the prognostic significance of preinfarction angina after a first Q wave myocardial infarction. Patients with anterior or inferior myocardial infarction were compared. BACKGROUND The effect of preinfarction angina on prognosis after anterior and inferior myocardial infarction remains unclear. METHODS A total of 291 patients with a first Q wave anterior (n = 171) or inferior (n = 120) myocardial infarction were examined to assess the effect of preinfarction angina on short- and long-term prognosis. The relation between predischarge left ventriculographic findings and preinfarction angina was also examined. RESULTS The presence of preinfarction angina was associated with lower peak creatine kinase activity, a lower in-hospital incidence of sustained ventricular tachycardia and fibrillation and a lower incidence of pump failure and cardiac mortality in patients with either anterior or inferior infarction. Among patients with anterior infarction, preinfarction angina was associated with a lower incidence of cardiac rupture and less need for readmission for heart failure within 1 year after the onset of infarction. In this subgroup it was also associated with a higher ejection fraction, a smaller end-diastolic volume and a lower incidence of aneurysm formation noted on ventriculography during convalescence. In patients with inferior infarction, these variables did not differ significantly in the presence or absence of preinfarction angina. Multivariate analysis confirmed that the presence of preinfarction angina was an independent predictor of development of ventricular aneurysm, late phase heart failure and 1-year cardiac mortality. CONCLUSIONS The presence of preinfarction angina has a favorable effect on infarct expansion and late phase left ventricular function, especially in patients with anterior myocardial infarction. The mechanisms responsible for this phenomenon are not known but may be secondary to limitations of infarct size through unidentified mechanisms other than collateralization (e.g., ischemic preconditioning).

Anisotropic Conduction Properties in Canine Atria Analyzed by High-Resolution Optical Mapping Preferential Direction of Conduction Block Changes From Longitudinal to Transverse With Increasing Age

Background—Anisotropic conduction properties may provide a substrate for reentrant arrhythmias. We investigated the age-dependent changes of structural and functional anisotropy in isolated right atria from infant (1 to 2 months), young (6 to 12 months), and old (6 to 10 years) dogs. Methods and Results—The histology of the mapped atrial tissues (a small subepicardial area, 2.8×4.2 mm) was characterized by an age-dependent increase of myofiber width and fat cell infiltration between myofibers. Cx43 was distributed homogeneously over the entire cell surface in infant dogs, whereas it progressively polarized to the cell termini with increasing age. The activation sequences were analyzed by high-resolution optical mapping using a voltage-sensitive dye. Activation fronts from the pacing site proceeded more rapidly along fiber orientation (longitudinal) than across it (transverse). Infant dogs showed “elliptical” isochrones with a smooth transition between longitudinal and transverse propagation, whereas old dogs had a “square” pattern with a sharp transition. Conduction block occurred predominantly during longitudinal propagation in infant dogs but during transverse propagation in old dogs. The shape of the wave front and the degree of lateral uncoupling seemed to decide the preferential direction of block. A zigzag activation causing an extremely slow transverse conduction was observed only in old dogs. Conclusions—Along with the age-dependent structural anisotropy, the preferential direction of block changed from longitudinal to transverse in association with a change in the wave front configuration. A zigzag propagation based on lateral uncoupling would predispose the elderly to multiple reentry and a higher incidence of atrial fibrillation.

Effects of inhibiting Na+/H+-exchange or angiotensin converting enzyme on atrial tachycardia-induced remodeling

BACKGROUND Inhibitors of the Na(+)/H(+)-exchanger (NHE1) and of angiotensin-converting enzyme (ACE) have been shown to reduce short-term (<6 h) tachycardia-induced atrial electrical remodeling. The role of NHE1 and ACE in longer-term electrical remodeling, as might occur with persistent AF, has not been studied. METHODS Dogs were subjected to atrial-tachypacing (400 bpm) for 7 days during treatment with 240 mg/day (standard clinical dose) of the NHE1 inhibitor cariporide (CariL, n=6), 1000 mg/day cariporide (CariH, n=6), 2 mg/kg/day of the ACE inhibitor enalapril (E, n=6), or no-drug controls (n=7). To ensure steady state concentrations at the onset of pacing, treatment began 3 days before the initiation of atrial tachypacing. Results were compared to those of unpaced dogs (n=9). RESULTS Atrial tachypacing reduced atrial effective refractory period (ERP), e.g. at a basic cycle length of 300 ms from 126+/-4 ms (unpaced, mean+/-S.E.) to 79+/-8 ms (no-drug controls, P<0.001). ERP abbreviation was unchanged by CariL (83+/-8 ms), CariH (80+/-7 ms), or E (76+/-5 ms). Atrial tachypacing increased mean duration of the longest AF episode in each dog (DAF) from 130+/-80 s (unpaced) similarly in all groups: 864+/-364 s, no-drug controls; 609+/-376 s, CariL; 709+/-353 s, CariH; 645+/-365 s, E (P=NS for differences among groups). Sustained AF requiring cardioversion for termination was induced in 0% of unpaced dogs vs. 33% of CariL, 33% of CariH, 33% of E, and 43% of control dogs. AF inducibility by single extrastimuli increased from 4+/-2% in unpaced dogs to 48+/-13% (P<0.01) in no-drug control dogs, an effect not changed by CariL (33+/-14%), CariH (35+/-17%) or E (48+/-16%). CONCLUSIONS In contrast to short-term (several-hour) atrial tachycardia-induced remodeling, remodeling by 7-day tachycardia is not affected by NHE1 or ACE inhibition. These results support the notion that short-term atrial tachycardia remodeling involves different mechanisms from longer-term remodeling, and urges caution in extrapolating results from studies of short-term remodeling to effects in longer-term remodeling as often occurs clinically.

Association between preinfarction angina and a lower risk of right ventricular infarction.

BACKGROUND Right ventricular infarction occurs in conjunction with inferior myocardial infarction caused by proximal occlusion of the right coronary artery. However, right ventricular infarction occurs infrequently, and the reasons for this are uncertain. METHODS We retrospectively assessed the association between preinfarction angina and right ventricular infarction, as well as the short-term outcome, in 113 patients with a first acute inferior myocardial infarction caused by right-coronary-artery occlusion. The association between the timing of angina during the week before infarction and the clinical outcome was also assessed. RESULTS The absence of preinfarction angina predicted the development of right ventricular infarction (odds ratio, 6.3; 95 percent confidence interval, 2.7 to 15.1; P<0.001), complete atrioventricular block (odds ratio, 3.6; 95 percent confidence interval, 1.4 to 10.3; P=0.01), and combined hypotension and shock (odds ratio, 12.4; 95 percent confidence interval, 4.5 to 40.6; P<0.001). Angina 24 to 72 hours before infarction was most strongly associated with reductions in the rates of right ventricular infarction (adjusted odds ratio, 0.2; 95 percent confidence interval, 0 to 0.8; P=0.02) and combined hypotension and shock (adjusted odds ratio, 0.1; 95 percent confidence interval, 0 to 0.5; P=0.02). CONCLUSIONS Preinfarction angina was an independent predictor of the absence of right ventricular infarction in patients with acute inferior myocardial infarction. The patients with preinfarction angina also had better short-term outcomes than those without preinfarction angina.

Randomized trial of angiotensin II-receptor blocker vs. dihydropiridine calcium channel blocker in the treatment of paroxysmal atrial fibrillation with hypertension (J-RHYTHM II Study)

AIMS Atrial fibrillation (AF) is a common arrhythmia frequently associated with hypertension. This study was designed to test the hypothesis that lowering blood pressure by angiotensin II-receptor blockers (ARB) has more beneficial effects than by conventional calcium channel blockers (CCB) on the frequency of paroxysmal AF with hypertension. METHODS AND RESULTS The Japanese Rhythm Management Trial II for Atrial Fibrillation (J-RHYTHM II study) is an open-label randomized comparison between an ARB (candesartan) and a CCB (amlodipine) in the treatment of paroxysmal AF associated with hypertension. Using daily transtelephonic monitoring, we examined asymptomatic and symptomatic paroxysmal AF episodes during a maximum 1 year treatment. The primary endpoint was the difference in AF frequency between the pre-treatment period and the final month of the follow-up. The secondary endpoints included cardiovascular events, development of persistent AF, left atrial dimension, and quality-of-life (QOL). The study enrolled 318 patients (66 years, male/female 219/99, 158 in the ARB group and 160 in the CCB group) treated at 48 sites throughout Japan. At baseline, the frequency of AF episodes (days/month) was 3.8 ± 5.0 in the ARB group vs. 4.8 ± 6.3 in the CCB group (not significant). During the follow-up, blood pressure was significantly lower in the CCB group than in the ARB group (P < 0.001). The AF frequency decreased similarly in both groups, and there was no significant difference in the primary endpoint between the two groups. There were no significant differences between the two groups in the development of persistent AF, changes in left atrial dimension, occurrence of cardiovascular events, or changes in QOL. CONCLUSIONS In patients with paroxysmal AF and hypertension, treatment of hypertension by candesartan did not have an advantage over amlodipine in the reduction in the frequency of paroxysmal AF (umin CTR C000000427).

Chest Compression-Only Cardiopulmonary Resuscitation for Out-of-Hospital Cardiac Arrest With Public-Access Defibrillation A Nationwide Cohort Study

Background—It remains unclear which is more effective to increase survival after out-of-hospital cardiac arrest in those with public-access defibrillation, bystander-initiated chest compression–only cardiopulmonary resuscitation (CPR) or conventional CPR with rescue breathing. Methods and Results—A nationwide, prospective, population-based observational study covering the whole population of Japan and involving consecutive out-of-hospital cardiac arrest patients with resuscitation attempts has been conducted since 2005. We enrolled all out-of-hospital cardiac arrests of presumed cardiac origin that were witnessed and received shocks with public-access automated external defibrillation (AEDs) by bystanders from January 1, 2005, to December 31, 2009. The main outcome measure was neurologically favorable 1-month survival. We compared outcomes by type of bystander-initiated CPR (chest compression–only CPR and conventional CPR with compressions and rescue breathing). Multivariable logistic regression was used to assess the relationship between the type of CPR and a better neurological outcome. During the 5 years, 1376 bystander-witnessed out-of-hospital cardiac arrests of cardiac origin in individuals who received CPR and shocks with public-access AEDs by bystanders were registered. Among them, 506 (36.8%) received chest compression–only CPR and 870 (63.2%) received conventional CPR. The chest compression–only CPR group (40.7%, 206 of 506) had a significantly higher rate of 1-month survival with favorable neurological outcome than the conventional CPR group (32.9%, 286 of 870; adjusted odds ratio, 1.33; 95% confidence interval, 1.03–1.70). Conclusions—Compression-only CPR is more effective than conventional CPR for patients in whom out-of-hospital cardiac arrest is witnessed and shocked with public-access defibrillation. Compression-only CPR is the most likely scenario in which lay rescuers can witness a sudden collapse and use public-access AEDs.