Troponin T, left ventricular mass, and function are excellent predictors of cardiovascular congestion in peritoneal dialysis
2006; Elsevier BV; Volume: 70; Issue: 3 Linguagem: Inglês
10.1038/sj.ki.5001605
ISSN1523-1755
AutoresAy.-M. Wang, CW Lam, Cheuk‐Man Yu, Mengyuan Wang, Ih.-S. Chan, Siu‐Fai Lui, John E. Sanderson,
Tópico(s)Acute Myocardial Infarction Research
ResumoPatients on maintenance peritoneal dialysis (PD) are frequently complicated with volume overload. In this study, we sought to evaluate troponin T testing alone or in combination with echocardiographic measures in predicting cardiovascular congestion in PD patients. This was a prospective study of 222 chronic PD patients with echocardiography and measurement of serum troponin T carried out at baseline. Patients were followed for 3 years or until death. The end point was first episode of cardiovascular congestion. Troponin T emerged as an independent predictor of cardiovascular congestion (hazard ratio, 2.98, 95% confidence intervals (CI), 1.19–7.42) in a multivariable Cox regression model, including also left ventricular mass index (LVMi) and ejection fraction (EF). Patients with troponin T>median (0.06 μg/l) and EF≤50% and patients with troponin T>median but EF>50% had a 3.10-fold (95% CI, 1.71–5.63) and 1.88-fold (95% CI, 1.05–3.38) adjusted risk of cardiovascular congestion, respectively, than those with troponin T≤median and EF>50%. Patients with troponin T>median and LVMi≥median (96.23 g/m2.7) had a 2.68-fold (95% CI, 1.39–5.19) adjusted risk of cardiovascular congestion than those with troponin T≤median and LVMi median (0.06 μg/l) and EF≤50% and patients with troponin T>median but EF>50% had a 3.10-fold (95% CI, 1.71–5.63) and 1.88-fold (95% CI, 1.05–3.38) adjusted risk of cardiovascular congestion, respectively, than those with troponin T≤median and EF>50%. Patients with troponin T>median and LVMi≥median (96.23 g/m2.7) had a 2.68-fold (95% CI, 1.39–5.19) adjusted risk of cardiovascular congestion than those with troponin T≤median and LVMi <median. In conclusion, troponin T predicts cardiovascular congestion in chronic PD patients without acute myocardial ischemia and provides incremental prognostic value for cardiovascular congestion when used in combination with LVM and EF. This easily available parameter adds significant value to echocardiography in identifying PD patients at risk of cardiovascular congestion. End-stage renal disease patients are at an accelerated risk of developing cardiovascular complications. According to a previous study by Harnett et al.,1.Harnett J.D. Foley R.N. Kent G.M. et al.Congestive-heart-failure in dialysis patients – prevalence, incidence, prognosis and risk-factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar up to a-third of the end-stage renal disease patients on dialysis developed heart failure on initiation of dialysis, of which 56% had further recurrences. Even for patients with no heart failure at baseline, around 25% was complicated with heart failure at a rate of 7% per year. More importantly, the presence of heart failure at initiation of dialysis and its recurrence were both significant predictors of mortality in patients on maintenance dialysis. Thus, the ability to early identify patients at risk of this complication may optimize therapeutic interventions, reduce this complication, and improve the adverse outcomes of dialysis patients. Echocardiography provides an assessment of left ventricular hypertrophy and dysfunction, and is an important tool in evaluating dialysis patients with heart failure and volume overload. Indeed, the presence of pre-existing systolic dysfunction predisposed dialysis patients to a greater risk of heart failure.1.Harnett J.D. Foley R.N. Kent G.M. et al.Congestive-heart-failure in dialysis patients – prevalence, incidence, prognosis and risk-factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar Experimental and clinical studies showed that necrosis- or apoptosis-mediated myocyte loss during ventricular remodeling may play a contributory role to the progression of left ventricular dysfunction.2.Goldspink D.F. Burniston J.G. Tan L.B. Cardiomyocyte death and the ageing and failing heart.Exp Physio. 2003; 88: 447-458Crossref PubMed Scopus (89) Google Scholar, 3.Nadal-Ginard B. Kajstura J. Leri A. Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure.Circ Res. 2003; 92: 139-150Crossref PubMed Scopus (410) Google Scholar, 4.Narula J. Haider N. Virmani R. et al.Apoptosis in myocytes in end-stage heart failure.N Engl J Med. 1996; 335: 1182-1189Crossref PubMed Scopus (1181) Google Scholar, 5.Olivetti G. Abbi R. Quaini F. et al.Apoptosis in the failing human heart.N Engl J Med. 1997; 336: 1131-1141Crossref PubMed Scopus (1397) Google Scholar, 6.Wencker D. Chandra M. Nguyen K. et al.A mechanistic role for cardiac myocyte apoptosis in heart failure.J Clin Invest. 2003; 111: 1497-1504Crossref PubMed Scopus (598) Google Scholar However, the study of this process requires myocardial biopsy, which is invasive and difficult to perform in humans. Measurement of serum biomarkers that reflect myocyte injury is relatively simple, noninvasive and may allow better characterization of the nature of cardiac disease. Among these different biomarkers, cardiac troponin T is a highly sensitive and specific marker of myocardial necrosis. Troponin T measurement is useful in diagnosing acute coronary syndrome7.Mair J. rtner-Dworzak E. Lechleitner P. et al.Cardiac troponin T in diagnosis of acute myocardial infarction.Clin Chem. 1991; 37: 845-852PubMed Google Scholar and is a powerful, independent risk marker in acute coronary syndrome.8.Ohman E.M. Armstrong P.W. Christenson R.H. et al.The GUST. Cardiac troponin T levels for risk stratification in acute myocardial ischemia.N Engl J Med. 1996; 335: 1333-1342Crossref PubMed Scopus (970) Google Scholar Troponin T is also increased in patients with heart failure and nonischemic disorders,9.Perna E.R. Macin S.M. Parras J.I. et al.Cardiac troponin T levels are associated with poor short- and long-term prognosis in patients with acute cardiogenic pulmonary edema.Am Heart J. 2002; 143: 814-820Abstract Full Text Full Text PDF PubMed Scopus (82) Google Scholar, 10.Del Carlo C.H. O'Connor C.M. Cardiac troponins in congestive heart failure.Am Heart J. 1999; 138: 646-653Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 11.Goto T. Takase H. Toriyama T. et al.Circulating concentrations of cardiac proteins indicate the severity of congestive heart failure.Heart. 2003; 89: 1303-1307Crossref PubMed Scopus (89) Google Scholar, 12.Setsuta K. Seino Y. Takahashi N. et al.Clinical significance of elevated levels of cardiac troponin T in patients with chronic heart failure.Am J Cardiol. 1999; 84: 608-611Abstract Full Text Full Text PDF PubMed Scopus (171) Google Scholar, 13.Perna E.R. Macin S.M. Canella J.P. et al.Ongoing myocardial injury in stable severe heart failure: value of cardiac troponin T monitoring for high-risk patient identification.Circulation. 2004; 110: 2376-2382Crossref PubMed Scopus (120) Google Scholar, 14.Lowbeer C. Gustafsson S.A. Seeberger A. et al.Serum cardiac troponin T in patients hospitalized with heart failure is associated with left ventricular hypertrophy and systolic dysfunction.Scand J Clin Lab Invest. 2004; 64: 667-676Crossref PubMed Scopus (40) Google Scholar, 15.Sato Y. Yamada T. Taniguchi R. et al.Serum concentration of cardiac troponin T in patients with cardiomyopathy: a possible mechanism of acute heart failure.Heart. 1998; 80: 209-210Crossref PubMed Scopus (15) Google Scholar and predicts prognosis in the nonrenal failure population with heart failure, suggesting that troponin T may be a marker of subclinical myocyte injury/necrosis. Circulating troponin T is frequently elevated in chronic kidney disease and dialysis patients without evidence of acute myocardial ischemia.16.Frankel W.L. Herold D.A. Ziegler T.W. Fitzgerald R.L. Cardiac troponin T is elevated in asymptomatic patients with chronic renal failure.Am J Clin Pathol. 1996; 106: 118-123Crossref PubMed Scopus (116) Google Scholar, 17.Ooi D.S. House A.A. Cardiac troponin T in hemodialyzed patients.Clin Chem. 1998; 44: 1410-1416PubMed Google Scholar Its elevation has been partly attributed to accumulation of troponin T fragments secondary to impaired renal clearance.18.Diris J.H.C. Hackeng C.M. Kooman J.P. et al.Impaired renal clearance explains elevated troponin T fragments in hemodialysis patients.Circulation. 2004; 109: 23-25Crossref PubMed Scopus (209) Google Scholar In patients with acute coronary syndrome, troponin T retains its prognostic significance even when renal function is impaired.19.Aviles R.J. Askari A.T. Lindahl B. et al.Troponin T levels in patients with acute coronary syndromes, with or without renal dysfunction.N Engl J Med. 2002; 346: 2047-2052Crossref PubMed Scopus (288) Google Scholar In addition, elevated troponin T shows important association with left ventricular hypertrophy and dysfunction,20.Mallamaci F. Zoccali C. Parlongo S. et al.Diagnostic value of troponin T for alterations in left ventricular mass and function in dialysis patients.Kidney Int. 2002; 62: 1884-1890Abstract Full Text Full Text PDF PubMed Scopus (65) Google Scholar and is predictive of mortality and cardiovascular death in end-stage renal disease patients on maintenance dialysis.21.Deegan P.B. Lafferty M.E. Blumsohn A. et al.Prognostic value of troponin T in hemodialysis patients is independent of comorbidity.Kidney Int. 2001; 60: 2399-2405Abstract Full Text Full Text PDF PubMed Scopus (55) Google Scholar, 22.Dierkes J. Domrose U. Westphal S. et al.Cardiac troponin T predicts mortality in patients with end-stage renal disease.Circulation. 2000; 102: 1964-1969Crossref PubMed Scopus (231) Google Scholar, 23.Defilippi C. Wasserman S. Rosanio S. et al.Cardiac troponin T and C-reactive protein for predicting prognosis, coronary atherosclerosis, and cardiomyopathy in patients undergoing long-term hemodialysis.JAMA. 2003; 290: 353-359Crossref PubMed Scopus (335) Google Scholar, 24.Apple F.S. Murakami M.M. Pearce L.A. Herzog C.A. Predictive value of cardiac troponin I and T for subsequent death in end-stage renal disease.Circulation. 2002; 106: 2941-2945Crossref PubMed Scopus (451) Google Scholar, 25.Roppolo L.P. Fitzgerald R. Dillow J. et al.A comparison of troponin T and troponin I as predictors of cardiac events in patients undergoing chronic dialysis at a veteran's hospital: a pilot study.J Am Coll Cardiol. 1999; 34: 448-454Abstract Full Text Full Text PDF PubMed Scopus (112) Google Scholar Given that troponin T represents a highly sensitive and specific marker of myocyte injury/necrosis and volume overload is a frequent complication in chronic peritoneal dialysis patients, we hypothesized that troponin T alone or in combination with left ventricular mass and ejection fraction (EF) may serve as important parameters that predict cardiovascular congestion in these patients. The baseline clinical, demographic, biochemical and dialysis characteristics are shown in Table 1. Eighty-five patients (38.3%) developed cardiovascular congestion during follow-up, of which 49 patients had 1 episode, 19 patients had 2 episodes and 17 patients had 3 or more episodes of cardiovascular congestion. Baseline median (interquartile range) troponin T was 0.1 (0.03, 0.2) μg/l for patients who subsequently developed cardiovascular congestion versus 0.03 (0.01, 0.09) μg/l for those who did not (P<0.001). Table 2 shows the baseline echocardiographic parameters. Troponin T showed positive correlations with left ventricular mass index (LVMi) by height2.7 (Spearman r=0.44, P<0.001), left ventricular volume in end-diastole index by body surface area (r=0.46, P<0.001), left ventricular posterior wall thickness in end-diastole (r=0.33, P<0.001), and interventricular septal wall thickness in end-diastole (r=0.30, P<0.001) and negative correlations with left ventricular EF (r=-0.32, P<0.001) and fractional shortening (r=-0.33, P<0.001).Table 1Baseline clinical, demographic, biochemical, and dialysis characteristicsAll patients (n=222)With cardiovascular congestion (n=85)No cardiovascular congestion (n=137)P-valueClinical and demographic data Male gender111 (50%)44 (51.8%)67 (48.9%)0.68 Age (years)56±1256.7±11.155.2±11.70.33 Body mass index (kg/m2)23.1±3.423.3±3.522.9±3.30.45 Positive history of smoking82 (36.9%)37 (43.5%)45 (32.8%)0.11 Diabetes mellitus67 (30.2%)35 (41.2%)32 (23.4%)0.005 Known clinical atherosclerotic vascular disease52 (23.4%)28 (32.9%)24 (17.5%)0.008 Renal diagnosis Chronic glomerulonephritis70 (31.5%)23 (27.1%)47 (34.3%)0.08 Diabetic nephropathy55 (24.8%)29 (34.1%)26 (19.0%)— Hypertensive nephrosclerosis29 (13.1%)11 (12.9%)18 (13.1%)— Others68 (30.6%)22 (25.9%)49 (33.6%)— Duration of dialysis, months26.5 (15, 51)25 (13, 49)30 (16, 56)0.10 Systolic blood pressure (mm Hg)147±17152±17143±16<0.001 Diastolic blood pressure (mm Hg)82±1083±1182±90.55 Medications use Erythropoietin90 (40.5%)38 (44.7%)52 (38%)0.32 Angiotensin converting enzyme inhibitor55 (24.8%)23 (27.1%)32 (23.4%)0.54 Beta-blocker116 (52.3%)46 (54.1%)70 (51.1%)0.66 Calcium channel blocker135 (60.8%)50 (58.8%)85 (62%)0.63 HMG-CoA reductase inhibitors31 (14%)14 (16.5%)17 (12.4%)0.40 Total number of anti-hypertensives1.53±0.961.67±0.981.45±0.940.09Biochemical data Hemoglobin (g/dl)9.14±1.688.62±1.609.46±1.66<0.001 Serum urea (mmol/l)24±1426±2223±60.17 Serum creatinine (μmol/l)1027±2741028±2461026±2910.96 Serum albumin (g/l)28.5±5.127.6±5.429.1±4.80.03 Calcium × phosphorus product (mmol2/l2)4.30±1.334.32±1.304.29±1.350.88 Parathyroid hormone (pmol/l)42 (19, 75)37 (19, 67)44 (18, 82)0.60 C-reactive protein (mg/l)2.78 (0.93, 9.03)3.20 (1.29, 7.07)2.25 (0.82, 10.01)0.36 Troponin T (μg/l)0.06 (0.01, 0.15)0.1 (0.03, 0.2)0.03 (0.01, 0.09)<0.001Dialysis indices data Total urea clearance1.81±0.431.78±0.441.83±0.430.48 Peritoneal dialysis urea clearance1.53±0.351.51±0.341.54±0.360.45 Total creatinine clearance, l/week per 1.73 m256.4±21.454.7±19.257.4±22.70.37 Residual GFR, ml/min per 1.73 m20.55 (0, 1.86)0.49 (0, 1.60)0.63 (0, 2.01)0.45 Daily urine volume(l)0.39±0.530.37±0.500.40±0.550.68 Net daily peritoneal dialysis ultrafiltration (l)0.95±0.970.88±0.980.99±0.960.42 Total net daily ultrafiltration (l)1.32±0.971.24±0.981.37±0.960.32 High transporter status by PET35 (15.9%)18 (21.4%)17 (12.5%)0.08GFR, glomerular filtration rate; PET, peritoneal equilibration test.Values are mean±s.d. or median (interquartile range). Open table in a new tab Table 2Baseline echocardiographic parametersAll patients (n=222)With cardiovascular congestion (n=85)No cardiovascular congestion (n=137)P-valueM-mode and 2-D LV mass index by height2.7 (g/m2.7)104±40117±4496±36<0.001 LV volume in end-diastole index by body surface area (ml/m2)65.9±20.373.6±22.761.1±17.1<0.001 LVPWd (cm)1.3±0.31.4±0.31.3±0.30.16 IVSd (cm)1.5±0.41.5±0.41.5±0.40.15 LV ejection fraction (%)52.5±8.350.3±9.953.9±6.80.001 LV fractional shortening (%)33.3±8.631.7±9.534.2±7.80.04 Patients with LV EF≤50%73 (32.9%)38 (44.7%)35 (25.5%)0.003 Left atrial diameter end-systole (cm)4.1±0.74.4±0.74.0±0.7 140 ms195 (90.7%)73 (89%)122 (91.7%) E/AbE/A ratio could be calculated in 212 patients (95%).0.9±0.51.0±0.60.9±0.40.26LV, left ventricular; LVPWd, left ventricular posterior wall thickness in end-diastole; IVSd, interventricular septal wall thickness in end-diastole; EF, ejection fraction; E, early diastolic transmitral flow velocity; A, late diastolic transmitral flow velocity; DT, deceleration time; E/A, ratio of early to late transmitral flow velocity.Values are mean±s.d.a Deceleration time could be assessed in 215 patients (97%).b E/A ratio could be calculated in 212 patients (95%). Open table in a new tab GFR, glomerular filtration rate; PET, peritoneal equilibration test. Values are mean±s.d. or median (interquartile range). LV, left ventricular; LVPWd, left ventricular posterior wall thickness in end-diastole; IVSd, interventricular septal wall thickness in end-diastole; EF, ejection fraction; E, early diastolic transmitral flow velocity; A, late diastolic transmitral flow velocity; DT, deceleration time; E/A, ratio of early to late transmitral flow velocity. Values are mean±s.d. The univariate Cox regression analysis for cardiovascular congestion is shown in Table 3. Table 4 displays the multivariable Cox regression models for cardiovascular congestion. Troponin T remained an independent predictor of cardiovascular congestion when adjusting for LVMi and EF in addition to other covariates in the base model (Model 3). Kaplan–Meier estimates of cardiovascular congestion-event free probability for all patients according to quartiles of troponin T are shown in Figure 1.Table 3Univariate Cox regression analysis for cardiovascular congestionVariablesHazard ratio (95% CI)P-valueAge1.01 (0.99–1.03)0.21Male gender1.17 (0.76–1.79)0.48Positive smoking history1.63 (1.06–2.51)0.026Dialysis duration0.995 (0.987–1.003)0.19Body mass index1.04 (0.97–1.11)0.25Clinical atherosclerotic vascular disease2.37 (1.50–3.74)<0.001Diabetes2.14 (1.38–3.30)0.001Serum albumin0.93 (0.89–0.97)0.002C-reactive protein1.00 (0.99–1.02)0.94Hemoglobin0.74 (0.64–0.86)<0.001Parathyroid hormone1.00 (1.00–1.01)0.95Calcium *phosphorus product1.04 (0.90–1.22)0.59Systolic blood pressure1.03 (1.02–1.04)<0.001Diastolic blood pressure1.01 (0.99–1.02)0.94High peritoneal transport1.62 (0.96–2.72)0.07Residual glomerular filtration rate0.89 (0.77–1.02)0.09Peritoneal dialysis urea clearance0.81 (0.45–1.45)0.47Left ventricular mass index1.012 (1.007–1.017)<0.001Left ventricular ejection fraction0.95 (0.93–0.97)<0.001Troponin T6.02 (3.10–11.68)<0.001CI, confidence interval. Open table in a new tab Table 4Multivariable Cox regression analysis of factors predicting cardiovascular congestionBase modelaCovariates considered in the initial model were age, diabetes mellitus, positive smoking history, background AVD, dialysis duration, systolic blood pressure, hemoglobin, serum albumin, residual glomerular filtration rate, and high peritoneal transport by peritoneal equilibration test.Model 1Model 2Model 3PHR (95% CI)PHR (95% CI)PHR (95% CI)PHR (95% CI)Hemoglobin (1 g/dl ↑)0.0160.84 (0.72, 0.97)0.0910.88 (0.76, 1.02)0.0640.87 (0.76, 1.01)0.0810.88 (0.76, 1.02)Serum albumin (1 g/l ↑)0.0100.94 (0.89, 0.99)0.0150.94 (0.90, 0.99)0.0140.94 (0.89, 0.99)0.0620.95 (0.90, 1.00)Diabetes mellitus0.0351.64 (1.03, 2.60)0.0361.64 (1.03, 2.61)0.1151.46 (0.91, 2.35)0.1671.40 (0.87, 2.26)Systolic blood pressure (1 mm Hg ↑)<0.0011.03 (1.01, 1.04)<0.0011.03 (1.01, 1.04)<0.0011.03 (1.01, 1.04) median and LVMi median (P median or ≤median and LVMi≥median and <median is shown in Table 5.Table 5Stepwise multivariable Cox regression analysis of predictors of cardiovascular congestion with patients stratified in four groups according to troponin T and LVMiPHazard ratios95% CIHemoglobin (1 g/dl ↑)0.0610.870.76, 1.01Serum albumin (1 g/l ↑)0.0190.940.89, 0.99Systolic blood pressure (mm Hg ↑)<0.0011.031.01, 1.04Known clinical atherosclerotic vascular disease0.0191.801.10, 2.95Left ventricular ejection fraction (% ↑)0.0320.9680.943, 0.997Troponin T and LVMi stratified in four groups (with troponin T≤median, LVMi median, LVMi <median vs troponin T≤median, LVMi <median0.0971.910.89, 4.10 Troponin T≤median, LVMi≥median vs troponin T≤median, LVMi < median0.1481.720.83, 3.58 Troponin T>median, LVMi≥median vs troponin T≤median, LVMi < median0.0032.681.39, 5.19CI, confidence intervals; LVMi, left ventricular mass index. Open table in a new tab CI, confidence intervals; LVMi, left ventricular mass index. Figure 3a shows the Kaplan–Meier estimates of cardiovascular congestion-event free probability for patients stratifying into four groups on the basis of troponin T≤median and >median and EF≤50% and >50%. The prevalence as well as frequency of recurrence of cardiovascular congestion during follow-up were the highest among patients with troponin T>median and EF≤50% (P median or ≤median and EF>50% and ≤50%.Table 6Stepwise multivariable Cox regression analysis of predictors of cardiovascular congestion with patients stratified in four groups according to troponin T and left ventricular ejection fractionP-valueHazard ratios95% CIHemoglobin (1 g/dl ↑)0.0480.650.75, 1.00Serum albumin (1 g/l ↑)0.0340.950.90, 1.00Systolic blood pressure (1 mm Hg ↑) 50% as reference group) troponin T>median, LVEF>50% vs troponin T≤median, LVEF>50%0.0341.881.05, 3.38 troponin T≤median, LVEF≤50% vs troponin T≤median, LVEF>50%0.3981.420.63, 3.19 troponin T>median, LVEF≤50% vs troponin T≤median, LVEF>50% 0.1 μg/l identifies a subgroup of end-stage renal disease patients with poor survival and high risk of cardiac death despite being asymptomatic.34.Khan N.A. Hemmelgarn B.R. Tonelli M. et al.Prognostic value of troponin T and I among asymptomatic patients with end-stage renal disease: a meta-analysis.Circulation. 2005; 112: 3088-3096Crossref PubMed Scopus (284) Google Scholar The exact mechanism of this association has remained unclear although study has indicated that patients with detectable circulating troponin T showed histologic changes, including patchy fibrosis and degenerative myocyte changes characteristics of heart failure.35.Ooi D.S. Isotalo P.A. Veinot J.P. Correlation of antemortem serum creatine kinase, creatine kinase-MB, troponin I, and troponin T with cardiac pathology.Clin Chem. 2000; 46: 338-344PubMed Google Scholar This gave additional evidence that an elevated troponin T in chronic peritoneal dialysis patients without acute myocardial ischemia may be indicative of subclinical myocardial necrosis or injury and warrants further evaluation. The causes of subclinical myocardial injury are not entirely clear although a number of factors including recurrent episodes of ischemia/infarction in patients with coronary artery disease, ventricular remodeling, abnormalities of the coronary microcirculation,10.Del Carlo C.H. O'Connor C.M. Cardiac troponins in congestive heart failure.Am Heart J. 1999; 138: 646-653Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar, 36.Ricchiuti V. Zhang J. Apple F.S. Cardiac troponin I and T alterations in hearts with severe left ventricular remodeling.Clin Chem. 1997; 43: 990-995PubMed Google Scholar and increased wall strain37.Logeart D. Beyne P. Cusson C. et al.Evidence of cardiac myolysis in severe nonischemic heart failure and the potential role of increased wall strain.Am Heart J. 2001; 141: 247-253Abstract Full Text Full Text PDF PubMed Scopus (117) Google Scholar have all been implicated to play a role in mediating the degradation of cardiac myocytes. Myocyte death/necrosis has been hypothesized to be important pathomechanisms for heart failure and contributes to progressive myocardial dysfunction and ventricular remodeling in the general population.2.Goldspink D.F. Burniston J.G. Tan L.B. Cardiomyocyte death and the ageing and failing heart.Exp Physio. 2003; 88: 447-458Crossref PubMed Scopus (89) Google Scholar, 3.Nadal-Ginard B. Kajstura J. Leri A. Anversa P. Myocyte death, growth, and regeneration in cardiac hypertrophy and failure.Circ Res. 2003; 92: 139-150Crossref PubMed Scopus (410) Google Scholar, 4.Narula J. Haider N. Virmani R. et al.Apoptosis in myocytes in end-stage heart failure.N Engl J Med. 1996; 335: 1182-1189Crossref PubMed Scopus (1181) Google Scholar, 5.Olivetti G. Abbi R. Quaini F. et al.Apoptosis in the failing human heart.N Engl J Med. 1997; 336: 1131-1141Crossref PubMed Scopus (1397) Google Scholar, 6.Wencker D. Chandra M. Nguyen K. et al.A mechanistic role for cardiac myocyte apoptosis in heart failure.J Clin Invest. 2003; 111: 1497-1504Crossref PubMed Scopus (598) Google Scholar However, it is currently not known whether similar pathologic process occurs in patients on dialysis. The evaluation of myocyte apoptosis/necrosis requires myocardial biopsy, which is invasive and not without risk. In contrast, troponin T measurement is routinely available in most hospital laboratories at a relatively low cost, is quick and noninvasive. It has the additional advantage of not being confounded by the presence of inflammation, unlike C-reactive protein. Heart failure and volume overload are frequent complications in chronic dialysis patients.1.Harnett J.D. Foley R.N. Kent G.M. et al.Congestive-heart-failure in dialysis patients – prevalence, incidence, prognosis and risk-factors.Kidney Int. 1995; 47: 884-890Abstract Full Text PDF PubMed Scopus (547) Google Scholar Pulmonary congestion was present in 80% of chronic peritoneal dialysis patients with volume overload.38.Tzamaloukas A.H. Saddler M.C. Murata G.H. et al.Symptomatic fluid retention in patients on continuous peritoneal dialysis.J Am Soc Nephrol. 1995; 6: 198-206PubMed Google Scholar Previous study by Zoccali et al. has reported the importance of left ventricular hypertrophy and systolic function as predictors of cardiovascular events in asymptomatic dialysis patients independent of other traditional and novel risk factors such as C-reactive protein and asymmetric dimethylarginine. Of note, patients with both left ventricular hypertrophy and systolic dysfunction showed the greatest risk of cardiovascular events.39.Zoccali C. Benedetto F.A. Mallamaci F. et al.Prognostic value of echocardiographic indicators of left ventricular systolic function in asymptomatic dialysis patients.J Am Soc Nephrol. 2004; 15: 1029-1037Crossref PubMed Scopus (144) Google Scholar As shown in our study, echocardiography provides an important evaluation of myocardial status and function in patients with cardiovascular congestion. The presence of more severe left ventricular hypertrophy and systolic dysfunction on echocardiography indeed predicts a higher subsequent risk of cardiovascular congestion. Of greater importance is the novel finding that troponin T provides additional prognostic value when used in combination with left ventricular hypertrophy and EF for predicting cardiovascular congestion in chronic peritoneal dialysis patients. The combination of troponin T with LVMi and EF identifies peritoneal dialysis patients with the greatest risk of cardiovascular congestion. Compared to patients with troponin T≤median and preserved left ventricular systolic function, those with troponin T>median but preserved left ventricular systolic function showed a nearly two-fold increase adjusted risk of cardiovascular congestion while those with troponin T≤median, but systolic dysfunction were at no greater risk of cardiovascular congestion. This suggests troponin T elevation has greater prognostic importance than depressed left ventricular systolic function in determining peritoneal dialysis patients at increased risk of cardiovascular congestion. In this study, the diagnosis of cardiovascular congestion was made by the attending physician, based on clinical and radiological evidence of pulmonary congestion without implications on the etiologic factor for the episode of cardiovascular congestion. A previous study by our group clearly showed that peritoneal dialysis patients with previous history of cardiovascular congestion, irrespective of the etiology, had greater left ventricular hypertrophy, dilatation and dysfunction.40.Wang A.Y. Sanderson J.E. Sea M.M. et al.Important factors other than dialysis adequacy associated with inadequate dietary protein and energy intake in maintenance peritoneal dialysis patients.Am J Clin Nutr. 2003; 77: 834-841PubMed Google Scholar Putting this together with our current finding that troponin T elevation was positively associated with left ventricular mass and negatively associated with left ventricular systolic function and was predictive of subsequent risk of cardiovascular congestion, our results may be interpreted in two ways. Firstly, an episode of cardiovascular congestion even though seemingly reversible with hypertonic exchanges may increase left ventricular hypertrophy, dysfunction, and myocardial damage. Secondly, patients with previous history of cardiovascular congestion may actually remain in a subclinical volume overload state persistently, thus resulting in greater left ventricular hypertrophy and dysfunction. Whichever is the case, troponin T elevation reflects the degree of left ventricular dysfunction more precisely than EF, thus explains its prognostic importance for cardiovascular congestion. Our results are well in keeping with recent study showing that severe coronary artery disease alone could not explain elevated troponin T in dialysis patients.41.Sharma R. Gaze D.C. Pellerin D. et al.Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T.Heart. 2006; 92: 804-809Crossref PubMed Scopus (72) Google Scholar Troponin T elevation reflects myocardial dysfunction and probably subclinical cellular damage as evidenced by left ventricular dilatation, impaired left ventricular systolic function, and raised left ventricular filling pressure.41.Sharma R. Gaze D.C. Pellerin D. et al.Cardiac structural and functional abnormalities in end stage renal disease patients with elevated cardiac troponin T.Heart. 2006; 92: 804-809Crossref PubMed Scopus (72) Google Scholar First, cardiovascular congestion was defined as such to include only episodes that require hospitalization. Patients presenting with milder symptoms of cardiovascular congestion such as ankle edema that do not require hospitalization were considered as event-free. This may result in an underestimation of the true incidence of cardiovascular congestion in our peritoneal dialysis patients. Second, echocardiography was not performed at the time of cardiovascular congestion. Thus, we were not able to determine whether cardiovascular congestion is due to cardiac dysfunction or fluid noncompliance. However, even with echocardiography this distinction is not easy. Third, a single troponin T was measured at study baseline and did not take into account of changes over time. Fourth, the study was performed in end-stage renal disease patients on maintenance peritoneal dialysis. Whether our results can also be generalized to hemodialysis patients and patients with other stages of chronic kidney disease need further evaluation. Our study has several important implications. First, given that troponin T remains a powerful predictor of cardiovascular congestion in chronic peritoneal dialysis patients independent of left ventricular mass and systolic function, this strengthens the utility of troponin T testing as a regular cardiovascular risk assessment and monitoring tool in peritoneal dialysis patients without acute myocardial ischemia. Second, the finding that troponin T testing has additional prognostic value to conventional echocardiographic parameters suggests troponin T should be measured in conjunction with echocardiography for cardiovascular risk stratification in order to identify peritoneal dialysis patients at risk of cardiovascular congestion. Third, in view that troponin T elevation in peritoneal dialysis patients may reflect subclinical myocardial injury rather than acute coronary syndrome, the correct troponin T cutoff for diagnosing acute coronary syndrome in peritoneal dialysis patients needs to be re-defined. Troponin T is a powerful, independent predictor for cardiovascular congestion and adds significant value to echocardiography in identifying peritoneal dialysis patients at risk of cardiovascular congestion.
Referência(s)