Warfarin Use and Increased Mortality in End-Stage Renal Disease

Background: Controversy exists regarding the benefits and risks of warfarin therapy in chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients. In this study, we assessed mortality and cardiovascular outcomes associated with warfarin treatment in patients with stages 3-5 CKD and ESRD admitted to the University of California-Irvine Medical Center. Methods: In a retrospective matched cohort study, we identified 59 adult patients with stages 3-6 CKD initiated on warfarin during the period 2011-2013, and 144 patients with stages 3-6 CKD who had indications for anticoagulation therapy but were not initiated on warfarin. All-cause mortality risk associated with warfarin treatment was estimated using Cox proportional hazard regression analysis, and the risk of significant bleeding and major adverse cardiovascular events were analyzed with Poisson regression analysis. Adjustment models were used to account for age, gender, diabetes mellitus, use of antiplatelet agents, and preexisting cardiovascular disease, and stratified by pre-dialysis CKD stages 3-5 vs. ESRD. Findings: During 5.8 years of follow-up, unadjusted mortality risk was higher in CKD patients on warfarin therapy (hazard ratio [HR] 2.34 with 95% CI 1.25-4.39; p < 0.01). After multivariate adjustment and stratification by CKD stage, the mortality risk remained significant in ESRD patients receiving warfarin (HR 6.62 with 95% CI 2.56-17.16; p < 0.001). Furthermore, adjusted rates of significant bleeding (incident rate ratio, IRR 3.57 with 95% CI 1.51-8.45; p < 0.01) and myocardial infarction (IRR 4.20 with 95% CI 1.78-9.91; p < 0.01) were higher among warfarin users. No differences in rates of ischemic or hemorrhagic strokes were found between the 2 groups. Conclusions: Warfarin use was associated with several-fold higher risk of death, bleeding, and myocardial infarction in dialysis patients. If additional studies suggest similar associations, the use of warfarin in dialysis patients warrants immediate reconsideration.

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Long Pentraxin 3 as a Broader Biomarker for Multiple Risk Factors in End-Stage Renal Disease: Association with All-Cause Mortality

Mediators of Inflammation ◽

10.1155/2019/3295725 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 3

Author(s):

Maria João Valente ◽

Susana Rocha ◽

Susana Coimbra ◽

Cristina Catarino ◽

Petronila Rocha-Pereira ◽

...

Keyword(s):

End Stage Renal Disease ◽

Renal Fibrosis ◽

Pentraxin 3 ◽

Dialysis Patients ◽

Inflammatory Biomarker ◽

Multiple Risk Factors ◽

All Cause Mortality ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Persistent inflammation in end-stage renal disease (ESRD) patients is known to underlie the progression of chronic kidney disease and to be associated with multiple risk factors including malnutrition, atherosclerosis, and cardiovascular disease (CVD). The acute-phase protein pentraxin 3 (PTX3) has a proven potential as a local inflammatory biomarker, but its clinical utility in ESRD remains unclear. Circulating levels of PTX3 and classical inflammatory mediators, including the clinical prototypical C-reactive protein (CRP), were assessed in 246 ESRD patients on dialysis and analysed in relation to the lipid profile, adipokine levels, and nutritional, cardiac, and renal fibrosis markers. Occurrence of deaths was recorded for the following year. Contrarily to the classical inflammatory markers, PTX3 levels were negatively correlated with nutritional markers and associated with a less atherogenic lipid profile. Levels of the cardiac and renal fibrosis markers and of the oxidized LDL/LDL-C ratio were found to be independent determinants of PTX3 concentration. When comparing inflammatory mediators, the increase in the PTX3 levels was the only predictor of all-cause mortality in dialysis patients in a survival model adjusted to all markers under study, other than the inflammatory ones, besides common confounding factors in dialysis. Data support the clinical applicability of PTX3 as a broader inflammatory biomarker than the classical ones, presenting a close association with inflammation, malnutrition, CVD, and renal fibrosis and a great potential to predict all-cause mortality in dialysis patients. The pleiotropic character of PTX3 may be of clinical relevance, and it could be targeted to ameliorate the high morbidity and mortality associated with ESRD.

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P1239SHORT- AND LONG-TERM OUTCOME OF END-STAGE RENAL DISEASE PATIENTS WITH ACUTE MYOCARDIAL INFARCTION

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa142.p1239 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hirota Kida ◽

Shungo Hikoso ◽

Akihiro Sunaga ◽

Oeun Bolrathanak ◽

Takayuki Kojima ◽

...

Keyword(s):

Myocardial Infarction ◽

End Stage Renal Disease ◽

Term Outcome ◽

Long Term Outcome ◽

All Cause Mortality ◽

Short And Long Term ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Abstract Background and Aims End-stage renal disease (ESRD) patients frequently have the coronary artery disease. However, the short- and long-term outcome of ESRD patients with acute myocardial infarction (AMI) is little known. The aim of this study was to clarify it. Method Using the database of the Osaka Acute Coronary Insufficiency Study (OACIS), 8702 consecutive AMI patients (male: 75.2%, mean age: 66.9±12.2yrs) from 2002 to 2013 were analyzed. We classified these patients into two groups, those with ESRD [ESRD group (n=271)] and without ESRD [No-ESRD group (n=8431)] and examined in-hospital or long-term all-cause mortality. ESRD was defined as eGFR<15ml/min/1.73m2. Results ESRD group had higher frequency of diabetes (59.3% vs 37.8%, p<0.01), hypertension (90.1% vs 63.3%, p<0.01), Killip class≧2 (40.1% vs 21%, p<0.01), multi-vessel disease (69.3% vs 50.8%, p<0.01), and lower frequency of peak CK>3000 (21.7% vs 32.4%, p<0.01) than No-ESRD group. Mean follow-up period was 1041±721 days. In hospital mortality of ESRD group was 27% and No-ESRD group 7.2%. In patients who discharged alive (8027 patients), 1-year mortality of ESRD group was 12.2% and No-ESRD group 3.3%, 3-year mortality of ESRD group was 29.3% and No-ESRD group 8.7%. Kaplan-Meier analysis revealed that the all-cause mortality (log-rank p<0.01) was significantly higher in ESRD group than No-ESRD group. In ESRD patients who discharged alive (203patients), Cox univariate analysis after multiple imputation revealed that peak CK>3000 was significantly associated with an increased risk of mortality (Hazard ratio 2.67, 95% confidence interval 1.18to 6.07, p=0.031). Conclusion In patients with AMI, ESRD was significantly associated with worse short- and long-term outcome, suggesting that careful treatment might be required in ESRD patients with AMI, especially had peak CK>3000.

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Lipid status association with 25-hydroxy vitamin D: Cross sectional study of end stage renal disease patients

Journal of Medical Biochemistry ◽

10.2478/jomb-2019-0032 ◽

2019 ◽

Vol 0 (0) ◽

Author(s):

Neda Milinković ◽

Marija Sarić ◽

Snežana Jovičić ◽

Duško Mirković ◽

Višnja Ležaić ◽

...

Keyword(s):

Vitamin D ◽

Peritoneal Dialysis ◽

End Stage Renal Disease ◽

Density Lipoprotein ◽

Dialysis Patients ◽

25 Hydroxy Vitamin D ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients ◽

Lipid Parameters

SummaryBackgroundSome observational studies indicate an association of 25-hydroxy vitamin D (25(OH)D) insufficiency and atherogenic cholesterol concentrations. The aim of this study was to investigate relationship between 25(OH)D concentrations and lipid parameters in end stage renal disease (ESRD) patients, separately for predialysis, hemodialysis and peritoneal dialysis patients.MethodsWe have adjusted 25(OH)D concentrations for seasonal variability with cosinor analysis, and performed all further analysis using these corrected 25(OH)D concentrations. Concentrations of 25(OH)D and the lipid parameters were determined in 214 ESRD patients and 50 control group participants. The analysis included the measurement of 25(OH)D by HPLC, apolipoprotein (Apo) AI, ApoB and Lp(a) by nephelometry, total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (TG) by spectrophotometry and manually calculated ApoB/ApoAI and LDL-C/HDL-C ratio.ResultsESRD patients with adjusted 25(OH)D concentrations of ≤ 50 nmol/L had significantly higher TC (P = 0.005) and ApoAI (P = 0.049). Significantly higher HDL-C (P = 0.011) and ApoAI (P = 0.020) were found in hemodialysis patients with the 25(OH)D concentrations of ≤ 50 nmol/L. The other analyzed lipid parameters differed significantly between predialysis, hemodialysis and peritoneal dialysis patients with 25(OH)D concentrations of < 50 nmol/L.ConclusionsOur study indicate the significant relationship between 25(OH)D repletion and optimal concentrations of lipid parameters in ESRD patients. Further research is necessary to explain whether joint evaluation of vitamin D status and lipid abnormalities could improve cardiovascular outcome in ESRD patients.

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Pulmonary hypertension in end-stage renal disease patients on dialysis and predialysis patients

Clinical & Investigative Medicine ◽

10.25011/cim.v43i3.34631 ◽

2020 ◽

Vol 43 (3) ◽

pp. E44-48

Author(s):

Yifu Li ◽

Yan Zhang ◽

Jinjun Wang ◽

Wenwei Chen ◽

Yong Cai ◽

...

Keyword(s):

Pulmonary Hypertension ◽

Cardiac Output ◽

Pulmonary Artery ◽

Renal Disease ◽

Pulmonary Artery Pressure ◽

End Stage Renal Disease ◽

Dialysis Patients ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Purpose: Pulmonary hypertension (PH) is a frequent and serious cardiovascular complication in patients with end-stage renal disease (ESRD) on dialysis. The purpose of this study was to investigate the prevalence of PH and its associated factors in patients with ESRD on maintenance dialysis and predialysis patients. Methods: The medical records of ESRD patients who underwent kidney transplantation between January 2011 and December 2017 were retrospectively reviewed. Demographic and clinical characteristics including echocardiographic findings before joining the waiting list for transplantation were evaluated and compared among groups divided according to dialysis or not and dialysis types. The results of transthoracic Doppler echocardiography were used to determine the pulmonary artery pressure. Pulmonary hypertension was defined as a systolic pulmonary artery pressure (sPAP) greater than 35 mmHg. Univariate and multivariate analyses were used to investigate factors associated with PH. Results: Data from 35 pre-dialysis patients with ESRD, 72 maintenance hemodialysis (HD) and 34 peritoneal dialysis (PD) patients were analysed. Pulmonary hypertension was 20.69% in pre-dialysis patients, 16.7% in HD patients and 14.7% in PD patients (P=0.957). There were negative correlations between sPAP and calcium (r=-0.230, P=0.012), Ca×P(r=-0.210, P=0.021), hemoglobin (r=-0.243, P=0.008) and a positive correlation between sPAP and cardiac output (r=0.481, P=0.000). Cardiac output (CO) was an independent risk factor of sPAP (B=1.431, confidence interval [CI] 95%: 0.687 to 2.175, P=0.000). Conclusion: Incidence of PH was not statistically different in ESRD patients on dialysis and pre-dialysis patients. Uremia may play a major role in the pathogenesis of PH in patients.

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Frailty severity is significantly associated with electrocardiographic QRS duration in chronic dialysis patients

PeerJ ◽

10.7717/peerj.1354 ◽

2015 ◽

Vol 3 ◽

pp. e1354 ◽

Cited By ~ 9

Author(s):

Chia-Ter Chao ◽

Jenq-Wen Huang

Keyword(s):

Regression Analysis ◽

Chronic Hemodialysis ◽

Self Report ◽

Qtc Interval ◽

Dialysis Patients ◽

Increased Risk ◽

Qrs Duration ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

End-stage renal disease (ESRD) patients are at increased risk of sudden cardiac death, the risk of which is presumably related to arrhythmia. Electrocardiographic (ECG) parameters have been found to correlate with arrhythmia and predict cardiovascular outcomes in ESRD patients. Frailty is also a common feature in this population. We investigate whether the severity of dialysis frailty is associated with ECG findings, including PR interval, QRS duration, and QTc interval. Presence and severity of frailty was ascertained using six different self-report questionnaires with proven construct validity. Correlation analysis between frailty severity and ECG was made, and those with significant association entered into multiple regression analysis for confirmation. Among a cohort of chronic hemodialysis patients, we found that frailty severity, assessed by the Edmonton frailty scale, is significantly associated with QRS duration (r= − 0.3,p< 0.05). Dialysis patients with QRS longer than 120 ms had significantly lower severity of frailty than those with QRS less than 120 ms (p= 0.01 for the Edmonton frailty scale and 0.05 for simple FRAIL scale). Regression analysis showed that frailty severity, assessed by the Edmonton frailty scale and simple FRAIL scale, was significantly associated with QRS duration independent of serum electrolyte levels. In conclusion, a significant relationship exists between the severity of frailty and QRS duration in ESRD patients. This might be an under-recognized link between frailty and its adverse cardiovascular impact in these patients.

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Abstract 16716: Comparison of Blood Troponin I Complexes and Free Form in Acute Myocardial Infarction and End Stage Renal Disease

Circulation ◽

10.1161/circ.142.suppl_3.16716 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Vikram Sharma ◽

Ruchi Sharma ◽

Shehab A Alansari ◽

Mohan L Maradumane ◽

Conner P Witherow ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Renal Disease ◽

End Stage Renal Disease ◽

Troponin I ◽

Mean Difference ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients ◽

Time Point

Introduction: Circulating blood troponin complexes and free fractions remain poorly characterised in different conditions where troponin is detectable in blood Hypothesis: The aim of the study was to compare the differences in troponin-I(TnI) complexes/free-forms in end stage renal disease (ESRD) compared to acute myocardial infarction(AMI) Methods: Blood was collected from patients with AMI(n=7) or ESRD(n=4) at two time points (a)As early as possible after AMI or at initial contact with ESRD patients and (b)24-48 hours later. Western blotting was carried out with HyTest cTnI-560cc antibody on plasma extracted from whole blood. Densitometry analysis was performed and evaluated using the independent samples T-test and paired T-test as appropriate Results: Prominent bands were noted at ~45,~37 and ~25 kDa respectively representing low molecular weight(LMW) TnI-TnT-TnC complex, binary TnI-TnC complex and free-TnI. At time-point (a), there was no difference in these bands between STEMI and CKD patients. Interestingly, at time-point (b), AMI patients had significantly lower intensity of the 45kDa and 37kDa bands compared to CKD patients(for 45 kDa band mean difference was 54.3±19.4 AU, p=0.02; for 37 kDa band mean difference was 27.7±10.5 AU, p=0.03) as well as compared to the initial STEMI samples taken at time-point (a)(for 45 kDa band mean difference was 41.4±8.1 AU, p=0.002; for 37 kDa band mean difference was 16.7±6.3 AU, p=0.002) ,however there was no difference in the 25kDa band Conclusions: AMI patients had progressively lesser quantities of circulating LMW-ITC and binary IC complexes following AMI compared to ESRD patients, but similar quantities of circulating free TnI. This indicates a constant release of LMW-ITC and binary-IC complexes from the myocardium or reduced glomerular filtration of these complexes in ESRD while in the AMI patients, the LMW-ITC and binary I-C complexes appear to be progressively eliminated from plasma after the initial release

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Forecasting the Incidence and Prevalence of Patients with End-Stage Renal Disease in Malaysia up to the Year 2040

International Journal of Nephrology ◽

10.1155/2017/2735296 ◽

2017 ◽

Vol 2017 ◽

pp. 1-5 ◽

Cited By ~ 10

Author(s):

Mohamad Adam Bujang ◽

Tassha Hilda Adnan ◽

Nadiah Hanis Hashim ◽

Kirubashni Mohan ◽

Ang Kim Liong ◽

...

Keyword(s):

Renal Disease ◽

End Stage Renal Disease ◽

Dialysis Patients ◽

Dialysis Treatment ◽

Forecasting Models ◽

Transplant Registry ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Background. The incidence of patients with end-stage renal disease (ESRD) requiring dialysis has been growing rapidly in Malaysia from 18 per million population (pmp) in 1993 to 231 pmp in 2013.Objective. To forecast the incidence and prevalence of ESRD patients who will require dialysis treatment in Malaysia until 2040.Methodology. Univariate forecasting models using the number of new and current dialysis patients, by the Malaysian Dialysis and Transplant Registry from 1993 to 2013 were used. Four forecasting models were evaluated, and the model with the smallest error was selected for the prediction.Result. ARIMA (0, 2, 1) modeling with the lowest error was selected to predict both the incidence (RMSE = 135.50, MAPE = 2.85, and MAE = 87.71) and the prevalence (RMSE = 158.79, MAPE = 1.29, and MAE = 117.21) of dialysis patients. The estimated incidences of new dialysis patients in 2020 and 2040 are 10,208 and 19,418 cases, respectively, while the estimated prevalence is 51,269 and 106,249 cases.Conclusion. The growth of ESRD patients on dialysis in Malaysia can be expected to continue at an alarming rate. Effective steps to address and curb further increase in new patients requiring dialysis are urgently needed, in order to mitigate the expected financial and health catastrophes associated with the projected increase of such patients.

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One-Year Mortality Rates in US Children with End-Stage Renal Disease

American Journal of Nephrology ◽

10.1159/000380828 ◽

2015 ◽

Vol 41 (2) ◽

pp. 121-128 ◽

Cited By ~ 23

Author(s):

Blanche M. Chavers ◽

Julia T. Molony ◽

Craig A. Solid ◽

Michelle N. Rheault ◽

Allan J. Collins

Keyword(s):

Peritoneal Dialysis ◽

Renal Disease ◽

End Stage Renal Disease ◽

Mortality Rates ◽

Transplant Recipients ◽

Dialysis Patients ◽

One Year ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Background/Aims: Few published data describe survival rates for pediatric end-stage renal disease (ESRD) patients. We aimed to describe one-year mortality rates for US pediatric ESRD patients over a 15-year period. Methods: In this retrospective cohort study, we used the US Renal Data System database to identify period-prevalent cohorts of patients aged younger than 19 for each year during the period 1995-2010. Yearly cohorts averaged approximately 1,200 maintenance dialysis patients (60% hemodialysis, 40% peritoneal dialysis) and 1,100 transplant recipients. Patients were followed for up to 1 year and censored at change in modality, loss to follow-up, or death. We calculated the unadjusted model-based mortality rates per time at risk, within each cohort year, by treatment modality (hemodialysis, peritoneal dialysis, transplant) and patient characteristics; percentage of deaths by cause; and overall adjusted odds of mortality by characteristics and modality. Results: Approximately 50% of patients were in the age group 15-18, 55% were male, and 45% were female. The most common causes of ESRD were congenital/reflux/obstructive causes (55%) and glomerulonephritis (30%). One-year mortality rates showed evidence of a decrease in the number of peritoneal dialysis patients (6.03 per 100 patient-years, 1995; 2.43, 2010; p = 0.0263). Mortality rates for transplant recipients (average 0.68 per 100 patient-years) were consistently lower than the rates for all dialysis patients (average 4.36 per 100 patient-years). Conclusions: One-year mortality rates differ by treatment modality in pediatric ESRD patients.

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Serum Sclerostin But Not DKK-1 Correlated with Central Arterial Stiffness in End Stage Renal Disease Patients

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17041230 ◽

2020 ◽

Vol 17 (4) ◽

pp. 1230 ◽

Cited By ~ 1

Author(s):

Chun-Feng Wu ◽

Jia-Sian Hou ◽

Chih-Hsien Wang ◽

Yu-Li Lin ◽

Yu-Hsien Lai ◽

...

Keyword(s):

Logistic Regression ◽

Regression Analysis ◽

Arterial Stiffness ◽

Renal Disease ◽

End Stage Renal Disease ◽

Serum Levels ◽

Control Group ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Sclerostin and dickkopf-1 (DKK1) played a role in the development of cardiovascular diseases and arterial stiffness in chronic kidney disease (CKD) patients but with controversial results of patients in end-stage renal disease (ESRD) including hemodialysis (HD) and peritoneal dialysis (PD). This study aimed to examine the association between the mode of dialysis or the values of sclerostin or DKK1 and carotid-femoral pulse wave velocity (cfPWV) in ESRD patients. There were 122 HD and 72 PD patients enrolled in this study. By a validated tonometry system, cfPWV was measured and then segregated patients into values of >10 m/s as the high central arterial stiffness (AS) group and values ≤ 10 m/s as the control group. Serum levels of sclerostin and DKK1 were measured using a commercial enzyme-linked immunosorbent assay kit. Possible risk factors for the development of AS were analyzed by logistic regression analysis. There were 21 (29.2%) of PD and 53 (43.4%) of HD in the high AS group. Compared to patients in the control group, those in the high AS group were older, had more comorbidities, had higher systolic blood pressure, and had higher serum levels of fasting glucose, C-reactive protein, and sclerostin. Levels of sclerostin (adjusted OR 1.012, 95% CI. 1.006–1.017, p = 0.0001) was found to be an independent predictor of high AS in ESRD patients by multivariate logistic regression analysis. Furthermore, receiver operating characteristic curve analysis showed the optimal cut-off values of sclerostin for predicting AS was 208.64 pmol/L (Area under the curve 0.673, 95% CI: 0.603–0.739, p < 0.001). This study showed that serum levels of sclerostin, but not DKK1 or mode of dialysis, to be a predictor for high central AS in ESRD patients.

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Cardiac Troponin T: Smaller Molecules in Patients with End-Stage Renal Disease than after Onset of Acute Myocardial Infarction

Clinical Chemistry ◽

10.1373/clinchem.2016.261644 ◽

2017 ◽

Vol 63 (3) ◽

pp. 683-690 ◽

Cited By ~ 20

Author(s):

Alma M A Mingels ◽

Eline P M Cardinaels ◽

Natascha J H Broers ◽

Anneke van Sleeuwen ◽

Alexander S Streng ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Renal Disease ◽

End Stage Renal Disease ◽

Cardiac Troponin ◽

Troponin T ◽

Cardiac Troponin T ◽

Stage Renal Disease ◽

End Stage ◽

Esrd Patients

Abstract BACKGROUND We have found previously that in acute myocardial infarction (AMI), cardiac troponin T (cTnT) is degraded in a time-dependent pattern. We investigated whether cTnT forms differed in patients with chronic cTnT increases, as seen with renal dysfunction, from those in the acute phase of myocardial infarction. METHODS We separated cTnT forms by gel filtration chromatography (GFC) in end-stage renal disease (ESRD) patients: prehemodialysis (pre-HD) and post-HD (n = 10) and 2 months follow-up (n = 6). Purified (cTnT) standards, quality control materials of the clinical cTnT immunoassay (Roche), and AMI patients' sera also were analyzed. Immunoprecipitation and Western blotting were performed with the original cTnT antibodies from the clinical assay and antibodies against the N- and C-terminal end of cTnT. RESULTS GFC analysis revealed the retention of purified cTnT at 27.5 mL, identical to that for cTnT in quality controls. For all ESRD patients, one cTnT peak was found at 45 mL, pre- and post-HD, and stable over time. Western blotting illustrated that this peak corresponded to cTnT fragments <18 kDa missing the N- and C-terminal ends. AMI patients' sera revealed cTnT peaks at 27.5 and 45 mL, respectively, corresponding to N-terminal truncated cTnT of 29 kDa and N- and C-terminal truncated fragments of <18 kDa, respectively. CONCLUSIONS We found that cTnT forms in ESRD patients are small (<18 kDa) and different from forms seen in AMI patients. These insights may prove useful for development of a more specific cTnT immunoassay, especially for the acute and diagnostic phase of myocardial infarction.

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