Masanori Nomura

Risk stratification using a combination of cardiac troponin T and brain natriuretic peptide in patients hospitalized for worsening chronic heart failure

We prospectively evaluated whether the combination of admission measurements of a marker for myocardial cell injury and a marker for left ventricular overload would effectively risk stratify patients with acutely decompensated heart failure. We measured serum concentrations of cardiac troponin T (cTnT) using a second-generation assay, as well as serum cardiac troponin I (cTnI) and plasma atrial and brain natriuretic peptide (BNP) concentrations on admission in 98 consecutive patients hospitalized for worsening chronic heart failure (mean age 69 years; 5 patients were in New York Heart Association functional class II, 35 were in class III, and 58 patients were in class IV). During a mean follow-up period of 451 days, there were 37 cardiac events, including 21 cardiac deaths (14 in-hospital deaths) and 16 readmissions for worsening heart failure. In a stepwise Cox regression analysis, including these biochemical markers, age, sex, functional class, and left ventricular ejection fraction, cTnT, and BNP were found to be significantly independent predictors of both cardiac death (p <0.05) and cardiac events (p <0.01). A cTnT >0.033 microg/L and/or a BNP >440 pg/ml on admission was correlated with an incremental increase in in-hospital cardiac mortality, overall cardiac mortality, and cardiac event rate. Kaplan-Meier analysis revealed that this combination could reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events. Measuring the combination of admission concentrations of cTnT and BNP may be a highly effective means of risk stratification of patients hospitalized for worsening chronic heart failure.

Intravascular ultrasound evaluation of coronary plaque regression by low density lipoprotein-apheresis in familial hypercholesterolemia: the Low Density Lipoprotein-Apheresis Coronary Morphology and Reserve Trial (LACMART).

OBJECTIVES We sought to assess the effects of low density lipoprotein (LDL)-apheresis (LDL-A) for regression of coronary plaque in familial hypercholesterolemia (FH), we set up a one-year follow-up multicenter trial using coronary angiography and intravascular ultrasound (IVUS). BACKGROUND It is still unclear whether aggressive lipid-lowering therapy by LDL-A leads to the regression of coronary plaque in patients with FH. METHODS Eighteen patients with FH were assigned to one of two groups: medication + LDL-A (LDL-A group, n = 11) and medication only (medication group, n = 7). Total cholesterol, triglycerides, high density lipoprotein cholesterol and LDL cholesterol were measured in all subjects at the outset of treatment (baseline) and every three months thereafter. Coronary angiography and IVUS were performed at the outset and after the one-year follow-up period to measure minimal lumen diameter (MLD) by coronary angiogram and plaque area (PA) by IVUS. RESULTS The LDL-A group showed 28.4% reduction in total cholesterol (from 275 +/- 27 mg/dl to 197 +/- 19 mg/dl) and 34.3% reduction in LDL cholesterol (from 213 +/- 25 mg/dl to 140 +/- 27 mg/dl) after one-year follow-up, while the medication group showed no changes in cholesterol levels. There were significant interactions between both treatments in total cholesterol (p = 0.0001), LDL cholesterol (p = 0.0001), MLD (p = 0.008) and PA (p = 0.017) using two-way repeated-measures analysis of variance by the SAS system (SAS Institute Inc., Cary, North Carolina). Significant differences were seen in net change in MLD (p = 0.004) and PA (p = 0.008) during the one-year follow-up period between both groups. CONCLUSIONS These results suggest that aggressive lipid-lowering therapy using the combination of LDL-A and lipid-lowering drugs may induce regression of coronary atherosclerotic plaque in FH patients.

Incidence and Risk Factors of Late Target Lesion Revascularization After Sirolimus-Eluting Stent Implantation (3-Year Follow-Up of the j-Cypher Registry)

It yet has not been clarified whether there is a late catch-up phenomenon in target lesion revascularization (TLR) after sirolimus-eluting stent (SES) compared to bare metal stent (BMS) implantation. In 12,824 patients enrolled in the j-Cypher Registry, incidences of early (within first year) and late (1 year to 3 years) TLR were compared between 17,050 lesions treated with SESs and 1,259 lesions treated with BMSs. Incidences of TLR in SES-treated lesions were 5.7% at 1 year, 8.1% at 2 years, and 10.0% at 3 years, whereas those in BMS-treated lesions were 14.2%, 15.5%, and 15.5%, respectively (p <0.0001, log-rank test). Incidences of late TLR were significantly higher with SESs compared to BMSs (2.6% vs 1.4% at 2 years and 4.5% vs 1.4% at 3 years, p = 0.0007, log-rank test). A multivariable logistic regression model identified 7 independent risk factors for late TLR at 3 years after SES implantation: hemodialysis, low estimated glomerular filtration rate, ostial right coronary artery, lesion length >or=30 mm, 2 stents for bifurcation, American Heart Association/American College of Cardiology type B2/C, and vessel size <2.5 mm. Of these, 5 factors were common to those for early TLR. In conclusion, a late catch-up phenomenon was observed as indicated by the increasing incidence of late TLR after SES, but not after BMS, implantation. Risk factors for late TLR were generally common to those for early TLR.

Cystatin C in Acute Heart Failure Without Advanced Renal Impairment

BACKGROUND The prognostic value of cystatin C relative to glomerular filtration rate (GFR) estimated by the Modification of Diet in Renal Disease Study (MDRD) equation modified for Japan has not been investigated in acute heart failure patients with normal to moderately impaired renal function. More accurate detection of mild renal impairment might improve the risk stratification of heart failure patients, especially patients with normal to moderately impaired renal function. METHODS Cystatin C and creatinine levels were measured on admission in 328 consecutive patients hospitalized for worsening chronic heart failure with a GFR estimated by MDRD equation modified for Japan >or=30 mL/min/1.73 m(2). RESULTS During a median follow-up period of 915 days, there were 52 (16%) cardiac deaths. In stepwise Cox regression analyses including cystatin C and GFR estimated by MDRD equation modified for Japan (either as continuous variables or as variables categorized into quartiles), cystatin C (P <.0001), but not GFR estimated by MDRD equation modified for Japan, was independently associated with cardiac mortality. Adjusted relative risk according to the quartiles of these markers and Kaplan-Meier analyses revealed that the cystatin C was a better marker to separate low-risk from high-risk patients. Furthermore, receiver-operating characteristic curve analyses of these markers revealed that cystatin C showed a higher precision in predicting cardiac mortality. CONCLUSION Measurements of cystatin C might improve early risk stratification compared with GFR estimated by MDRD equation modified for Japan in acute heart failure patients with normal to moderately impaired renal function.

Pentraxin 3 in unstable angina and non-ST-segment elevation myocardial infarction

PURPOSE We prospectively investigated the prognostic value of pentraxin 3 (PTX3) in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). BACKGROUND PTX3 may be a useful marker for localized vascular inflammation and damage to the cardiovascular system. Recent studies have shown that plasma PTX3 is elevated in patients with UA/NSTEMI; however, its prognostic value in UA/NSTEMI remains unclear. METHODS PTX3, high-sensitivity C-reactive protein (hsCRP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and cardiac troponin I were measured on admission in 204 consecutive patients (mean age of 69 years; 144 males) hospitalized for UA/NSTEMI within 24h (mean of 7.5h) after the onset of chest symptoms. A cardiac event, which was defined as cardiac death, rehospitalization for acute coronary syndrome (ACS), or rehospitalization for worsening heart failure, was monitored for 6 months after admission. RESULTS A total of 26 (13%) cardiac events occurred during the 6-month follow-up period. In a stepwise Cox regression analysis including 18 well-known clinical and biochemical predictors of ACS outcome, both PTX3 (relative risk 3.86 per 10-fold increment, P=0.01) and NT-proBNP (relative risk 2.16 per 10-fold increment, P=0.02), but not hsCRP, were independently associated with the 6-month cardiac event. The cardiac event rate was higher in patients with increased PTX3 (> or = 3.1ng/mL of median value) than those without (20% vs. 5.8%, P=0.003). A Kaplan-Meier analysis revealed that patients with increased PTX3 had a higher risk for cardiac events than those without (P=0.002). CONCLUSION PTX3 and NT-proBNP may be potent and independent predictors for 6-month cardiac events in patients hospitalized for UA/NSTEMI within 24h after the onset. Measurement of plasma PTX3 may substantially improve the early risk stratification of patients with UA/NSTEMI.

Risk stratification using serum concentrations of cardiac troponin T in patients with end-stage renal disease on chronic maintenance dialysis.

BACKGROUND It has been recently suggested that cardiac troponin T (cTnT) may be more sensitive than troponin I (cTnI) for subclinical myocardial cell injury in patients on chronic dialysis. METHODS We prospectively compared the predictive value of cTnT with cTnI, atrial (ANP) and brain natriuretic peptide (BNP) in 100 consecutive outpatients on chronic dialysis without acute coronary syndromes over a period of 3 months, and assessed whether the combination of cTnT with clinical information including age, duration of dialysis, and medical histories was useful for risk stratification of these patients. During the 2-year follow-up period, 19 patients died, mostly due to cardiac causes (53%). RESULTS The area under the receiver operator characteristic (ROC) curve for the cTnT as predictor of both overall and cardiac death was significantly greater than the area under the cTnI curve (p < 0.0001 and p = 0.01), the BNP curve (p < 0.001 and p < 0.01) or the ANP curve (p < 0.0001 and p < 0.005). In a stepwise multivariate Cox regression analysis, only cTnT (p < 0.05 and p < 0.01) and a history of heart failure requiring hospitalization (p < 0.05 and p < 0.005) were independent predictors of both all cause and cardiac mortality. Using parameters of cTnT > or =0.1 microg/l and/or history of heart failure, the overall and cardiac mortality rate for the low risk group (n=66) were 4.5% and 1.5%, respectively, 40% and 16% for the intermediate risk group (n=25), and 67% and 56% for the high risk group (n=9). CONCLUSION cTnT concentrations offer a higher prognostic accuracy than cTnI, ANP and BNP in patients on chronic dialysis. The combination of elevated cTnT and a history of heart failure may be a highly effective means of risk stratification of these patients.

Use of percutaneous cardiopulmonary support of patients with fulminant myocarditis and cardiogenic shock for improving prognosis.

Percutaneous cardiopulmonary support was used in 9 patients with fulminant myocarditis and cardiogenic shock. Although 2 of the patients died, 7 improved and were able to resume social activities. Percutaneous cardiopulmonary support should be administered routinely to patients with fulminant myocarditis developing into cardiogenic shock.

Early detection of successful coronary reperfusion based on serum myoglobin concentration: Comparison with serum creatine kinase isoenzyme MB activity

The usefulness of serum myoglobin (Mb) concentration for early detection of successful reperfusion was compared with that of creatine kinase isoenzyme MB (CKMB) activity in 49 patients with acute myocardial infarction. To determine accurately the time of reperfusion, we performed coronary angiography every 5 minutes during reperfusion therapy. Reperfusion was obtained in 32 patients (reperfused group) but not in 17 patients (nonreperfused group) until 60 minutes after the initiation of reperfusion therapy. Blood samples were taken before and 15, 30, and 60 minutes after the angiographic confirmation of reperfusion in the reperfused group. In the nonreperfused group, samples were taken before and 15, 30, and 60 minutes after the initiation of treatment. We calculated the Mb ratio (value after reperfusion or treatment initiation to value before) and CKMB ratio (value after to value before). When values > 2.4 for the Mb ratio or > 2.0 for the CKMB ratio were used as the criteria for reperfusion within 60 minutes after initiation of treatment, the sensitivities were 91% and 56% at 15 minutes after reperfusion, 97% and 84% at 30 minutes, and 100% and 100% at 60 minutes, respectively. For each ratio the specificity of detection was 100% at all times evaluated. Thus the Mb ratio accurately detected the success of reperfusion as early as 15 minutes after reperfusion and may be more useful than the CKMB ratio for detecting the success of reperfusion within 30 minutes.

Circulating high-mobility group box 1 and cardiovascular mortality in unstable angina and non-ST-segment elevation myocardial infarction

OBJECTIVE High-mobility group box 1 (HMGB1) is a damage-associated molecular pattern molecule, which suggests a potential role of this protein in the pathophysiology of acute coronary syndrome (ACS). Circulating HMGB1 has been shown to be independently associated with cardiac mortality in ST-segment elevation myocardial infarction. However, its prognostic value remains unclear in unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI). METHODS HMGB1, high-sensitivity C-reactive protein (hsCRP), cardiac troponin I and B-type natriuretic peptide concentrations were measured on admission in 258 consecutive patients (mean age of 67 years) hospitalized for UA/NSTEMI within 24h (mean, 7.4h) of the onset of chest symptoms. RESULTS A total of 38 (14.7%) cardiovascular deaths, including 10 in-hospital deaths, occurred during a median follow-up period of 49 months after admission. In a stepwise Cox regression analysis including 19 well-known clinical predictors of ACS, HMGB1 [relative risk (RR) 3.24 per 10-fold increment; P = 0.0003], cardiac troponin I (RR 1.83 per 10-fold increment, P = 0.0007), Killip class>1 (RR 4.67, P = 0.0001) and age (RR 1.05 per 1-year increment, P = 0.03), but not hsCRP, were independently associated with cardiovascular mortality. In-hospital and cardiovascular mortality rates were higher in patients with increased HMGB1 (≥ 2.4 ng/mL of median value) than those without increased HMGB1 (6.3% vs. 1.5%, P = 0.04; and 23% vs. 6.9%, P = 0.0003). CONCLUSION Circulating concentration of HMGB1 on admission may be a potential and independent predictor of cardiovascular mortality in patients hospitalized for UA/NSTEMI within 24h of onset.

Early detection of successful coronary reperfusion based on serum concentration of human heart-type cytoplasmic fatty acid-binding protein

Both human heart-type cytoplasmic fatty acid-binding protein (H-FABPc) and myoglobin are low molecular weight proteins that are abundant in the cytoplasm of myocardial cells. Unlike myoglobin, H-FABPc content in the skeletal muscle is less than in cardiac muscle. To investigate the usefulness of the serum concentration of H-FABPc in the early detection of successful coronary reperfusion, we measured serum concentrations of H-FABPc and myoglobin in 45 patients with acute myocardial infarction treated with intracoronary thrombolysis or direct percutaneous transluminal coronary angioplasty. Coronary angiography was performed every 5 min for reperfusion therapy to identify the onset of reperfusion. Reperfusion, defined as a TIMI grade 2 or 3, was achieved within 60 min of the initiation of reperfusion therapy in 30 patients (the reperfused group), but was not achieved in 15 patients (the non-reperfused group). Blood samples were obtained before initiation of treatment and 15, 30 and 60 min after initiation of treatment in the non-reperfused group. In the reperfused group, samples were obtained before reperfusion and 15, 30 and 60 min after reperfusion. The H-FABPc ratio (the ratio of value after to value before the initiation of treatment or reperfusion) increased sharply after the onset of reperfusion, peaking at 41 +/- 18 min, and decreased rapidly thereafter. The predictive accuracy of an H-FABPc ratio of > 1.8 for the detection of reperfusion within 60 min of the initiation of treatment was 93% at 15 min after reperfusion, 98% at 30 min, and 100% at 60 min. Similar rates of predictive accuracy were observed for a myoglobin ratio > 2.4. The H-FABPc ratio detected successful reperfusion as early as 15 min after the onset of reperfusion and was highly accurate in detecting reperfusion within 60 min of the onset of reperfusion. The predictive accuracy of the H-FABPc ratio was similar to that of the myoglobin ratio for the early detection of successful coronary reperfusion.