Protocatechuic acid prevents isoproterenol-induced heart failure in mice by downregulating kynurenine-3-monooxygenase.

Protocatechuic acid (3,4-dihydroxybenzoic acid) prevents oxidative stress, inflammation and cardiac hypertrophy. This study aimed to investigate the therapeutic effects of protocatechuic acid in an isoproterenol-induced heart failure mouse model and to identify the underlying mechanisms. To establish the heart failure model, C57BL/6NTac mice were given high-dose isoproterenol (80 mg/kg body weight) for 14 days. Echocardiography revealed that protocatechuic acid reversed the isoproterenol-induced downregulation of fractional shortening and ejection fraction. Protocatechuic acid attenuated cardiac hypertrophy as evidenced by the decreased heart-weight-to-body-weight ratio and the expression of Nppb. RNA sequencing analysis identified kynurenine-3-monooxygenase (Kmo) as a potential target of protocatechuic acid. Protocatechuic acid treatment or transfection with short-interfering RNA against Kmo ameliorated transforming growth factor ß1-induced upregulation of Kmo, Col1a1, Col1a2 and Fn1 in vivo or in neonatal rat cardiac fibroblasts. Kmo knockdown attenuated the isoproterenol-induced increase in cardiomyocyte size, as well as Nppb and Col1a1 expression in H9c2 cells or primary neonatal rat cardiomyocytes. Moreover, protocatechuic acid attenuated Kmo overexpression-induced increases in Nppb mRNA levels. Protocatechuic acid or Kmo knockdown decreased isoproterenol-induced ROS generation in vivo and in vitro. Thus, protocatechuic acid prevents heart failure by downregulating Kmo. Therefore, protocatechuic acid and Kmo constitute a potential novel therapeutic agent and target, respectively, against heart failure.

A novel polymer-free everolimus-eluting stent with a nitrogen-doped titanium dioxide film inhibits restenosis and thrombosis in a swine coronary model.

BACKGROUND: Short-term outcomes regarding the safety and efficacy of a polymer-free everolimus-eluting stent (EES) with a nitrogen-doped titanium dioxide (N-TiO2) film in a swine coronary model have been reported. However, the long-term results of the use of this type of stent have not yet been evaluated or compared to those of other polymer-free coronary stents. Therefore, this study aimed to determine the mid- to long-term safety and efficacy of a polymer-free EES with an N-TiO2 film in a swine coronary model. METHODS: Polymer-free EES with N-TiO2 films (n = 30) and polymer-free sirolimus-eluting stents (SES; n = 30) were implanted in 30 pigs. Quantitative coronary analysis and optical coherence tomography were conducted immediately and at 1 (quantitative coronary analysis only), 3, and 6 months after stenting. Histopathologic examinations were performed at 1, 3, and 6 months after stenting. RESULTS: The polymer-free EES group had a lower percentage of neointimal growth than the polymer-free SES group at 3 months (22.5% ± 11.4% vs. 32.1% ± 12.3%; p < 0.001). The polymer-free EES group had a lower fibrin score than the polymer-free SES group at 1 month (1.9 ± 0.45 vs. 2.5 ± 0.54; p = 0.001). The re-endothelialization rates were similar between groups. The polymer-free EES group had a lower percentage of the area of stenosis than the polymer-free SES group throughout the follow-up period. CONCLUSIONS: The novel polymer-free EES with an N-TiO2 film has superior safety and efficacy than the polymer-free SES at the 6-month follow-up in a swine model.

Long-term clinical outcomes in patients with acute myocardial infarction complicated by cardiogenic shock according to the application and initiation time of extracorporeal membrane oxygenation in South Korea.

BACKGROUND: Limited data are available regarding the proper application time and long-term outcomes of extracorporeal membrane oxygenation (ECMO) in patients with cardiogenic shock. This cohort study appraised the clinical outcomes according to ECMO application without or before cardiopulmonary resuscitation (CPR) in patients with acute myocardial infarction (AMI) combined with cardiogenic shock. METHODS: Between 2011 and 2015, a total of 13,104 patients with AMI were enrolled in a nationwide AMI registry. Eligible patients with cardiogenic shock, who underwent percutaneous coronary intervention, with a 3-year clinical follow-up, were analyzed. The 949 included patients were divided into two groups: no ECMO (n = 845) and ECMO application (n = 104). The ECMO group was further divided into ECMO without or before CPR (n = 11) and ECMO after CPR (n = 93). RESULTS: Significant differences were noted in major adverse cardiac events (MACEs) between the no ECMO and ECMO application groups during the 3-year follow-up (41.5% vs. 80.8%; p < 0.001). However, the ECMO without or before CPR group showed similar outcomes to the no ECMO group in 3-year MACEs (63.6% vs. 41.5%; p = 0.055). MACEs during 3 years of follow-up were significantly lower in the ECMO without or before CPR group than in the ECMO after CPR group (63.6% vs. 82.8%; p = 0.005). CONCLUSIONS: A significantly lower risk of major cardiac events in ECMO without or before CPR suggests that early application of ECMO can be a reasonable strategy to improve outcomes in patients with AMI complicated by cardiogenic shock.

Syringic acid mitigates isoproterenol-induced cardiac hypertrophy and fibrosis by downregulating Ereg.

Gallic acid has been reported to mitigate cardiac hypertrophy, fibrosis and arterial hypertension. The effects of syringic acid, a derivative of gallic acid, on cardiac hypertrophy and fibrosis have not been previously investigated. This study aimed to examine the effects of syringic acid on isoproterenol-treated mice and cells. Syringic acid mitigated the isoproterenol-induced upregulation of heart weight to bodyweight ratio, pathological cardiac remodelling and fibrosis in mice. Picrosirius red staining, quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting analyses revealed that syringic acid markedly downregulated collagen accumulation and fibrosis-related factors, including Fn1. The results of RNA sequencing analysis of Ereg expression were verified using qRT-PCR. Syringic acid or transfection with si-Ereg mitigated the isoproterenol-induced upregulation of Ereg, Myc and Ngfr. Ereg knockdown mitigated the isoproterenol-induced upregulation of Nppb and Fn1 and enhancement of cell size. Mechanistically, syringic acid alleviated cardiac hypertrophy and fibrosis by downregulating Ereg. These results suggest that syringic acid is a potential therapeutic agent for cardiac hypertrophy and fibrosis.

Long-term clinical outcomes of type 1 vs. type 2 myocardial infarction in patients who underwent angiography: data from the Korea acute myocardial infarction-national institute of health registry.

Background: In the cause of increase the clinical research observational evidence on type 2 myocardial infraction (T2MI), the study compared the characteristics of T2MI and T1MI with respect to major adverse cardiac events (MACE) and mortality as long-term outcomes from a large, nationwide, prospective Korean cohort registry. Methods: From 13,105 consecutively enrolled individuals in the Korea Acute Myocardial Infarction-National Institute of Health (KAMIR-NIH) registry between October 2011 and December 2015, 11,053 acute myocardial infarction (AMI) patients were divided into the T1MI (n=10,545) and T2MI (n=508) groups. All patients completed ≥3 years of follow-up. Results: The Kaplan-Meier curve analysis and Cox proportional hazard regression models showed that the cumulative rate of MACE was similar between the 2 groups (11.4% vs. 13.4%, log-rank P=0.185) at 3 years. However, the T2MI group showed higher rates of all-cause death [12.6% vs. 9.4%, log-rank P=0.019; hazard ratio (HR), 1.42; 95% CI: 1.08-1.85; P=0.012] and non-cardiac death (3.5% vs. 5.3%, log-rank P=0.043; HR, 1.55; 95% CI: 1.01-2.37; P=0.043) than the T1MI group. Male sex (HR 1.540; 95% CI: 1.218-1.947, P<0.001), old age (≥65 years; HR, 3.546; 95% CI: 2.645-4.753, P<0.001), low hemoglobin level (<12 g/dL; HR, 2.335; 95% CI: 1.841-2.961, P<0.001), high heart rate (>100 beats/min; HR, 1.852; 95% CI: 1.436-2.388, P<0.001), low glomerular filtration rate (GFR) (<60 mL/min/1.73 m2; HR, 2.373; 95% CI: 1.874-3.005, P<0.001), high body mass index (>25 kg/m2; HR, 0.644; 95% CI: 0.514-0.805, P<0.001), and low left ventricular ejection fraction (LVEF) (<40%; HR, 1.487; 95% CI: 1.095-2.020, P=0.011) were the independent predictors for 3-year non-cardiac mortality. Conclusions: Although the 2 groups did not differ in MACE, the total mortality rate was higher in T2MI than in T1MI, especially non-cardiac mortality. The independent predictors for non-cardiac mortality were male sex, old age, anemia, low GFR, tachycardia, obesity, and low LVEF.

Comparison of Prognosis According to the Use of Emergency Medical Services in Patients with ST-Segment Elevation Myocardial Infarction.

PURPOSE: This study aimed to compare long-term clinical outcomes according to the use of emergency medical services (EMS) in patients with ST-segment elevation myocardial infarction (STEMI) who arrived at the hospital within 12 hr of symptom onset. MATERIALS AND METHODS: A total of 13104 patients with acute myocardial infarction were enrolled in the Korea Acute Myocardial Infarction Registry-National Institutes of Health from October 2011 to December 2015. Of them, 2416 patients with STEMI who arrived at the hospital within 12 hr were divided into two groups: 987 patients in the EMS group and 1429 in the non-EMS group. Propensity score matching (PSM) was performed to reduce bias from confounding variables. After PSM, 796 patients in the EMS group and 796 patients in the non-EMS group were analyzed. The clinical outcomes during 3 years of clinical follow-up were compared between the two groups according to the use of EMS. RESULTS: The symptom-to-door time was significantly shorter in the EMS group than in the non-EMS group. The EMS group had more patients with high Killip class compared to the non-EMS group. The rates of all-cause death and major adverse cardiac events (MACE) were not significantly different between the two groups. After PSM, the rate of all-cause death and MACE were still not significantly different between the EMS and non-EMS groups. The predictors of mortality were high Killip class, renal dysfunction, old age, long door-to-balloon time, long symptom-to-door time, and heart failure. CONCLUSION: EMS utilization was more frequent in high-risk patients. The use of EMS shortened the symptom-to-door time, but did not improve the prognosis in this cohort.

Preclinical Evaluation of a Novel Polymer-free Everolimus-eluting Stent in a Mid-term Porcine Coronary Restenosis Model.

BACKGROUND: Titanium dioxide films exhibit good biocompatibility and may be effective as drug-binding matrices for drug-eluting stents. We conducted a mid-term evaluation of a novel polymer-free everolimus-eluting stent using nitrogen-doped titanium dioxide film deposition (TIGEREVOLUTION®) in comparison with a commercial durable polymer everolimus-eluting stent (XIENCE Alpine®) in a porcine coronary restenosis model. METHODS: Twenty-eight coronary arteries from 14 mini-pigs were randomly allocated to TIGEREVOLUTION® stent and XIENCE Alpine® stent groups. The stents were implanted in the coronary artery at a 1.1-1.2:1 stent-to-artery ratio. Eleven stented coronary arteries in each group were finally analyzed using coronary angiography, optical coherence tomography, and histopathologic evaluation 6 months after stenting. RESULTS: Quantitative coronary analysis showed no significant differences in the pre-procedural, post-procedural, and 6-month lumen diameters between the groups. In the volumetric analysis of optical coherence tomography at 6 months, no significant differences were observed in stent volume, lumen volume, and percent area stenosis between the groups. There were no significant differences in injury score, inflammation score, or fibrin score between the groups, although the fibrin score was zero in the TIGEREVOLUTION® stent group (0 vs. 0.07 ± 0.11, P = 0.180). CONCLUSION: Preclinical evaluation, including optical coherence tomographic findings 6 months after stenting, demonstrated that the TIGEREVOLUTION® stent exhibited efficacy and safety comparable with the XIENCE Alpine® stent, supporting the need for further clinical studies on the TIGEREVOLUTION® stent.

Protocatechuic acid attenuates isoproterenol-induced cardiac hypertrophy via downregulation of ROCK1-Sp1-PKCγ axis.

Cardiac hypertrophy is an adaptive response of the myocardium to pressure overload or adrenergic agonists. Here, we investigated the protective effects and the regulatory mechanism of protocatechuic acid, a phenolic compound, using a mouse model of isoproterenol-induced cardiac hypertrophy. Our results demonstrated that protocatechuic acid treatment significantly downregulated the expression of cardiac hypertrophic markers (Nppa, Nppb, and Myh7), cardiomyocyte size, heart weight to body weight ratio, cross-sectional area, and thickness of left ventricular septum and posterior wall. This treatment also reduced the expression of isoproterenol-induced ROCK1, Sp1, and PKCγ both in vivo and in vitro. To investigate the mechanism, we performed knockdown and overexpression experiments. The knockdown of ROCK1, Sp1, or PKCγ decreased the isoproterenol-induced cell area and the expression of hypertrophic markers, while the overexpression of Sp1 or PKCγ increased the levels of hypertrophic markers. Protocatechuic acid treatment reversed these effects. Interestingly, the overexpression of Sp1 increased cell area and induced PKCγ expression. Furthermore, experiments using transcription inhibitor actinomycin D showed that ROCK1 and Sp1 suppression by protocatechuic acid was not regulated at the transcriptional level. Our results indicate that protocatechuic acid acts via the ROCK1/Sp1/PKCγ axis and therefore has promising therapeutic potential as a treatment for cardiac hypertrophy.

Long-Term Outcomes of Patients With Late Presentation of ST-Segment Elevation Myocardial Infarction.

BACKGROUND: Real-world data on baseline characteristics, clinical practice, and outcomes of late presentation (12 to 48 h of symptom onset) in patients with ST-segment elevation myocardial infarction (STEMI) are limited. OBJECTIVES: This study aimed to investigate real-world features of STEMI late presenters in the contemporary percutaneous coronary intervention (PCI) era. METHODS: Of 13,707 patients from the Korea Acute Myocardial Infarction Registry-National Institutes of Health database, 5,826 consecutive patients diagnosed with STEMI within 48 h of symptom onset during 2011 to 2015 were categorized as late (12 to 48 h; n = 624) or early (<12 h; n = 5,202) presenters. Coprimary outcomes were 180-day and 3-year all-cause mortality. RESULTS: Late presenters had remarkably worse clinical outcomes than early presenters (180-day mortality: 10.7% vs. 6.8%; 3-year mortality: 16.2% vs. 10.6%; both log-rank p < 0.001), whereas presentation at ≥12 h of symptom onset was not independently associated with increased mortality after STEMI. The use of invasive interventional procedures abruptly decreased from the first (<12 h) to the second (12 to 24 h) 12-h interval of symptom-to-door time ("no primary PCI strategy" increased from 4.9% to 12.4%, and "no PCI" from 2.3% to 6.6%; both p < 0.001). Mortality rates abruptly increased from the first to the second 12-h interval of symptom-to-door time (from 6.8% to 11.2% for 180-day mortality; from 10.6% to 17.3% for 3-year mortality; all p < 0.05). CONCLUSIONS: Data from a nationwide prospective Korean registry reveal that inverse steep differences in the use of invasive interventional procedures and mortality rates were found between early and late presenters after STEMI. A multidisciplinary approach is required in identifying late presenters of STEMI who can benefit from invasive interventional procedures until further studied.

Higher Long-Term Mortality in Patients with Non-ST-Elevation Myocardial Infarction than ST-Elevation Myocardial Infarction after Discharge.

PURPOSE: This study aimed to compare mortality rates after discharge between the patients with non-ST-elevation myocardial infarction (NSTEMI) and those with ST-elevation myocardial infarction (STEMI), and identify each mortality risk factors in these two types of myocardial infarction. MATERIALS AND METHODS: Between 2011 and 2015, 13105 consecutive patients were enrolled in the Korea Acute Myocardial Infarction-National Institute of Health registry (KAMIR-NIH); 12271 patients with acute myocardial infarction met the inclusion criteria and were further stratified into the STEMI (n=5828) and NSTEMI (n=6443) groups. The occurrence of mortality and cardiac mortality at 3 years were compared between groups, and the factors associated with mortality for NSTEMI and STEMI were evaluated. RESULTS: The comparison between these two groups and long-term follow-up outcomes showed that the cumulative rates of all-cause and cardiac mortality were higher in the NSTEMI group than in the STEMI group [all-cause mortality: 10.9% vs. 5.8%; hazards ratio (HR), 0.464; 95% confidence interval (CI), 0.359-0.600, p<0.001; cardiac mortality: 6.6% vs. 3.5%, HR, 0.474; 95% CI, 0.344-0.654, p<0.001, respectively). In the NSTEMI group, low left ventricular ejection fraction (LVEF; <40%), no percutaneous coronary intervention (PCI), old age (≥65 years), and low hemoglobin level (<12 g/dL) were identified as risk factors for 3-year mortality. In the STEMI group, old age, low glomerular filtration rate (<60 mL/min/1.73 m²), low LVEF, high heart rate (>100 beats/min), no PCI, and low hemoglobin level were identified as the risk factors for 3-year mortality. CONCLUSION: The NSTEMI group had higher mortality compared to the STEMI group during the 3-year clinical follow-up after discharge. Low LVEF and no PCI were the main risk factors for mortality in the NSTEMI group. In contrast, old age and renal dysfunction were the risk factors for long-term mortality in the STEMI group.

Clinical characteristics of spontaneous coronary artery dissection in young female patients with acute myocardial infarction in Korea.

BACKGROUND/AIMS: We aimed to evaluate the prevalence, characteristics, and clinical outcomes of spontaneous coronary artery dissection (SCAD) in young female patients with acute myocardial infarction (AMI). METHODS: We identified 8,250 patients diagnosed with AMI who underwent coronary angiogram from the Chonnam National University Hospital database, Gwangju, Korea, between November 2005 and September 2017. A total of 148 female patients aged less than 60 years with a history of AMI were retrospectively studied and the characteristics and clinical outcomes were evaluated for all SCAD patients. RESULTS: Among female patients with AMI aged less than 60 years, the prevalence of SCAD was 8.78% (13 of 148). Based on the angiographic classification, type 2 SCAD was most commonly observed on angiograms in 69.2% of the cases (nine of 13), followed by type 3 in 23.1% (three of 13), and type 1 in 7.7% (one of 13). Furthermore, the left anterior descending (LAD) artery was the most commonly affected coronary artery (76.9%, 10 of 13 cases) and the distal segments of the coronary arteries were the most common sites of SCAD (92.3%, 12 of 13). Regarding the clinical outcomes, one of 13 patients experienced repeat revascularization during the following 31 months. CONCLUSION: The prevalence of SCAD was 8.7%, indicating that SCAD is not rare, among female patients aged less than 60 years with AMI in Korea. Type 2 SCAD was most commonly observed on angiogram. Moreover, the distal portion of the LAD was the segment most commonly affected by SCAD. The long-term clinical outcomes were favorable in patients surviving SCAD.

Long-Term Clinical Outcome according to Changes of Glomerular Filtration Rate in AMI Patients with Multivessel Disease after Percutaneous Coronary Intervention.

Glomerular filtration rate (GFR) is an important indicator of renal failure. However, regarding delta GFR in acute myocardial infarction (AMI) is rare. In this study, it was examined whether the delta GFR had an adverse effect on outcomes in patients with AMI and multivessel disease (MVD). Among 13,105 consecutive patients enrolled in the Korea Acute Myocardial Infarction-National Institute of Health registry, 2619 with AMI and MVD who underwent percutaneous cardiac intervention (PCI) were assigned to the better delta GFR (group I, n=1432 [54.7%]) or worse delta GFR (group II, n=1187 [45.3%]) groups and followed for 3 or more years. The mean age of group I was lower than that of group II (62.64±11.52 years vs. 64.29±11.64 years; p<0.001). On multivariate analysis, delta GFR (hazard ratio, 1.50; 95% confidence interval, 1.05-2.13; p=0.024) was a negative risk factor for adverse cardiac events. Age over 65 years (p<0.001), history of MI (p=0.008), low hemoglobin (p<0.001), high triglyceride (p=0.008), low high-density lipoprotein cholesterol (p=0.002), and low left ventricular ejection fraction (LVEF) (p<0.001) were prognostic factors for major adverse cardiac events (MACE). In patients with a GFR <60 mL/min/1.73 m2, mortality was increased by 0.9% in the multivessel PCI group and 0.7% in the IRA-only PCI group at the 1-year follow-up. According to the 3-year clinical follow-up analysis, prognosis was better in better delta GFR patients with AMI and MVD who underwent PCI than in worse delta GFR patients.

Impact of Previous Angina on Clinical Outcomes in ST-Elevation Myocardial Infarction Underwent Percutaneous Coronary Intervention.

The present study sought to assess the impact of previous angina symptoms on real world clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who had undergone successful percutaneous coronary interventions using drug-eluting stents (DES). Patients were selected from 13,650 consecutive patients enrolled in the Korea Acute Myocardial Infarction-National Institute of Health (KAMIR-NIH) registry. A total of 5167 STEMI patients were divided into a previous-angina group (n=1129) and a control group (n=4038). Major adverse cardiac and cerebrovascular events (MACCEs) that included all-cause death, recurrent myocardial infarction (re-MI), repeat PCI, coronary artery bypass graft (CABG), cerebrovascular accident (CVA). Among the 5167 patients with STEMI, MACCEs had occurred in 168 patients in the previous-angina group (14.9%) and 726 patients in the control group (18.0%) (HR, 0.76, 95% CI, 0.60-0.96, p=0.019) at the two-year (800-day) for clinical outcomes. Previous angina was associated with better clinical outcomes with respect to all-cause death (HR, 0.65, 95% CI, 0.44-0.96, p=0.029) and cardiac death (HR, 0.52, 95% CI, 0.31-0.84, p=0.008). Previous angina was a negative risk factor for adverse cardiac events. A previous history of angina predisposes a patient to a favorable outcome after acute myocardial infarction (AMI) in patients with DES implantation.

Association between omentin and echo parameters in patients with chronic heart failure.

BACKGROUND: Adipose-derived adipokines have been demonstrated to be associated with the development of experimental heart disease through chronic inflammation and cardiac cell apoptosis. Omentin is to be one of the novel adipokines. The aim of this study is to investigate the relationship between circulating omentin and cardiac dysfunction in patients with chronic heart failure (CHF). METHODS: A total of 189 CHF patients were studied, determining serum omentin and echocardiographic parameters. All participants were divided into two experimental groups: the 111 patients who had a left ventricular ejection fraction (EF) ≥40% (EF-H) and the 78 patients exhibiting EF values <40% (EF-L). RESULTS: The EF-L group showed significantly higher circulating omentin levels compared to the EF-H group (210.8±67.2 vs. 155.3±45.3, P<0.001; Student's t-test). Overall, the data of the linear regression analysis revealed that serum omentin levels correlated positively with left atrial diameters (r=0.31, P=0.006), left ventricular end-systolic dimensions (r=0.42, P<0.001), and left ventricular end-diastolic dimensions (r=0.38, P=0.002) and negatively with left ventricular EF (r=-0.45, P=0.001; Spearmen's rank correlations coefficients for each). The multiple regression model included all variables at p<0.1 by the univariate analysis. A multiple logistic regression analysis demonstrated that high levels of patients' serum omentin were associated with cardiac dysfunction in patients with CHF (OR=1.22; 95% CI: 0.91-1.58; P=0.009). CONCLUSIONS: These findings suggested that elevated serum omentin levels were only very mildly related to the changes in cardiac volume and function in CHF patients. Further studies are then needed to assess the real clinical value of omentin in this setting.

Increased Circulating Cathepsin K in Patients with Chronic Heart Failure.

Cysteinyl cathepsin K (CatK) is one of the most potent mammalian collagenases involved in cardiovascular disease. Here, we investigated the clinical predictive value of serum CatK levels in patients with chronic heart failure (CHF). We examined 134 patients with CHF, measuring their serum CatK, troponin I, high-sensitive C-reactive protein, and pre-operative N-terminal pro-brain natriuretic peptide levels. The patients were divided into two groups: the 44 patients who showed a left ventricular (LV) ejection fraction (LVEF) < 40% (the "lowLVEF" group) and the 90 patients showing LVEF values ≥ 40% (the "highLVEF" group). The lowLVEF patients had significantly higher serum CatK levels compared to the highLVEF patients (58.4 ± 12.2 vs. 44.7 ± 16.4, P < 0.001). Overall, a linear regression analysis showed that CatK levels correlated negatively with LVEF (r = -0.4, P < 0.001) and positively with LV end-diastolic dimensions (r = 0.2, P < 0.01), LV end-systolic dimensions (r = 0.3, P < 0.001), and left atrial diameters (r = 0.3, P < 0.01). A multiple logistic regression analysis showed that CatK levels were independent predictors of CHF (odds ratio, 0.90; 95% confidence interval, 0.84-0.95; P < 0.01). These data indicate that elevated levels of CatK are closely associated with the presence of CHF and that the measurement of circulating CatK provides a noninvasive method of documenting and monitoring the extent of cardiac remodeling and dysfunction in patients with CHF.