Elevated heart rate at twelve months after heart transplantation is an independent predictor of long term mortality

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1 Elevated heart rate at twelve months after heart transplantation is an independent predictor of long term mortality C. Tomas, MA Castel, E Roig, I. Vallejos, C. Plata, F. Pérez-Villa Cardiology Department, Thorax Institute, Hospital Clinic, Barcelona, Spain ESC CONGRESS 2010 STOCKHOLM

2 No disclosures DISCLOSURES

3 BACKGROUND Synus tachycardia due to graft denervation is frequent in patients receiving a heart transplantation (HTx). Elevated heart rate (HR) is associated to higher mortality in ischemic patients, heart failure patients and HTx recipients. It is unknown if elevated HR can affect cardiac allograft function in the long-term follow-up.

4 BACKGROUND It is unclear if sinus tachycardia in HTx patients should be pharmacological treated.

5 AIMS To evaluate the role of the heart rate at 6 and 12 months after HTx in predicting HTx long-term outcome

6 METHODS Observational, retrospective, single-center analysis of a prospective register of 208 HTx performed from 1999 to 2009 Patients dying during the first six months after HTx were excluded from the analysis (acute mortality) HR was analyzed from ECG registered at 6 and 12 months after HTx during routine outpatients visits

7 METHODS Routine left heart catheterization was performed at 12 months after HTx and in further follow-up to assess graft vasculopathy Mode of death was recorded in all patients by autopsy, hospital records or family interrogation Endomyocardial biopsies were performed routinely during the first 6 months after HTx and if acute rejection suspected

8 METHODS Univariate analysis was performed with baseline characteristics from recipients, donors, intraoperative variables and adverse events Multivariate cox regression analysis was performed with variables known to have an influenced upon mortality and those selected from the univariate analysis. Kaplan-Meier curves were used for survival analysis

9 RESULTS Receptors baseline characteristics: All patients n=208 Acute deaths: 34, acute mortality (first 6 months after HTx): 16% Final study cohort n=172 Age, yrs 53.4±11 Male, n (%) 140 (81.4) Mean HR at 6 months, bpm 86.1±14 Mean HR at 12 months, bpm 84.5±14 BMI 25.8±4.1 Aetiology, n(%) Ischemic Dilated non Ischemic Valvular Restrictive Hypertrophic Acute myocarditis Re-do HTx 70 (41) 55 (32) 11 (6.4) 3 (1.7) 4 (2.3) 4 (2.3) 2 (1.2)

10 RESULTS Receptors baseline characteristics: Blood Group, n (%) A B AB 0 75(43.6) 19 (11) 7(4.1) 71(41.3) Diabetes Tobacco abuse previous year Previous neoplasia Renal Insufficiency 41 (24) 23 (13.4) 7 (4.1) 51 (30) Previous sternotomy, n (%) 35 (20.3) IABP or VAD, n (%) 47 (27.3) CMV-positive Toxoplasma-positive EBV-positive Immunosuppression, n (%) Induction therapy Initial Cyclosporine Initial Tachrolimus Steroids 143 (83.1) 129 (75) 156 (95) 147 (99) 70 (41) 77 (53.5) 111 (75)

11 Donors baseline characteristics: RESULTS Age (yrs) 34.7±13.7 Male, n (%) 128 (74.4) BMI 26±13.8 Intra- and post-operative data: Graft ischemia time (min) 186±51 Pump time (min) 121±31 Urgent Htx 46 (26.7)

12 RESULTS OUTCOMES Mean survival time (yrs) Median survival time (yrs) 6 ± ± 3.1 Deaths, n (%) 31 (18) Cause of death: Acute/hyperacute rejection 3 (9.7) Graft vasculopathy 8 (25.8) Sudden death 5 (16.1) Infection 4 (13) Malignancy 4 (13) CVA 2 (6.5) Other 5 (16)

13 RESULTS OUTCOMES Graft vasculopathy, n (%) 30 (19.2) Acute rejection, n (%) 96 (56) Acute rejection with hemodynamic compromise 12 (6.9)

14 RESULTS UNIVARIATE ANALYSIS p HR 95% CI Receptor Age (yrs) Functional class (NYHA) Ischemic aetiology: Heart rate at 6 months (bpm) Heart rate at 12 months (bpm) < Diabetes mellitus Serum creatinine (mg/dl) Bilirrubin Previous Malignancy Previous Tobacco abuse Recipient CMV-pos Recipient EBV-pos Recipient Toxoplasma-pos Adverse Events: Graft vasculopathie Acute Rejection Rejection with hemodinamic compromise Donor age

15 RESULTS UNIVARIATE ANALYSIS p HR 95% CI Receptor Age (yrs) Functional class (NYHA) Ischemic aetiology: Heart rate at 6 months (bpm) Heart rate at 12 months (bpm) < Diabetes mellitus Serum creatinine (mg/dl) Bilirrubin Previous Malignancy Previous Tobacco abuse Recipient CMV-pos Recipient EBV-pos Recipient Toxoplasma-pos Adverse Events: Graft vasculopathie Acute Rejection Rejection with hemodinamic compromise Donor age

16 RESULTS MULTIVARIATE COX REGRESSION ANALYSIS FOR RISK OF DEATH RISK FACTOR HR 95% I for HR Lower Upper Heart rate at 12 months (bpm) P

17 RESULTS MULTIVARIATE COX REGRESSION ANALYSIS FOR RISK OF DEATH RISK FACTOR HR 95% CI for HR Lower Upper Heart rate at 12 months (bpm) Highest quartile of HR at 12 m (HR> 94/m) P No correlation of HR with development of allograft vasculopathie or mode of death

18 RESULTS SURVIVAL FOR QUARTILES OF HR AT 12 MONTHS HTX P<0.001

19 LIMITATIONS Single center Limited number of patients and events Lack of complete assessment of diastolic dysfunction

20 CONCLUSIONS I In our series, elevated heart rate measured at 12 months after HTx is an independent predictor of mortality in HTx recipients. There was no correlation between HR and mode of death or presence of graft vasculopathy. A HR >94 bpm identifies patients at high risk at mid-long term.

21 CONCLUSIONS II It is to elucidate if HR in HTx is a risk marker or a risk factor. In this subset of patients a pharmacological treatment to slow HR might be indicated.

22 THANK YOU FOR YOUR ATTENTION! By Jesús Martin Vicente

23 THANK YOU FOR YOUR ATTENTION! By Jesús Martin Vicente

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