Original Report: Patient-Oriented, Translational Research American
Journal of
Nephrology
Received: August 10, 2010 Accepted: August 27, 2010 Published online: September 30, 2010
Am J Nephrol 2010;32:432–438 DOI: 10.1159/000320755
Right Ventricular Dysfunction in Patients with End-Stage Renal Disease Francesco Paneni a Mario Gregori a Giuseppino Massimo Ciavarella a Sebastiano Sciarretta a Luciano De Biase a Laura Marino a Giuliano Tocci a Francesco Principe b Alessandro Domenici b Remo Luciani b Giorgio Punzo b Paolo Menè b Massimo Volpe a, c
Divisions of a Cardiology and b Nephrology, 2nd Faculty of Medicine, University of Rome ‘Sapienza’, Sant’Andrea Hospital, Rome, and c IRCCS Neuromed, Polo Molisano, University of Rome ‘Sapienza’, Pozzilli, Italy
Key Words Arteriovenous fistula ⴢ Dialysis ⴢ Pulmonary hypertension ⴢ Right ventricular dysfunction
Abstract Background: While chronic dialysis treatment has been suggested to increase pulmonary pressure values, right ventricular dysfunction (RVD) is a major cause of death in patients with end-stage renal disease. We investigated the impact of different dialysis treatments on right ventricular function. Methods: We examined 220 subjects grouped as follows: healthy controls (n = 100), peritoneal dialysis (PD; n = 26), hemodialysis (HD) with radial arteriovenous fistula (AVF; n = 62), and HD with brachial AVF (n = 32). Echocardiography including tissue Doppler imaging (TDI) of the right ventricle was performed in all patients. Results: Pulmonary pressure values progressively rose from controls across the 3 dialysis groups (21.7 8 6.8, 29.7 8 6.7, 37.9 8 6.7 and 40.8 8 6.6 mm Hg, respectively; p ! 0.001). TDI indices of right ventricular function were more impaired in HD patients, particularly in those with brachial AVF. RVD, assessed by TDI myocardial performance index, was higher in HD patients compared with PD patients (71.3 vs. 34.6%, p ! 0.001). Moreover, the
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prevalence of RVD further increased in patients with brachial AVF compared with the radial access (90.6 vs. 61.3%, p ! 0.001). Conclusions: Compared to DP, HD increases the risk of RVD, particularly in the presence of brachial AVF. TDI may detect early functional failure of the right ventricle in HD patients. Copyright © 2010 S. Karger AG, Basel
Introduction
Cardiovascular disease is the leading cause of mortality in patients undergoing dialysis, accounting for 50% of deaths [1]. In particular, heart failure is the most common finding in these patients and is associated with poor prognosis [2]. Hemodialysis (HD) which is usually carried out via a surgically created native arteriovenous fistula (AVF) has been associated with an increased risk of pulmonary hypertension [3–6], a condition reported as a predictor of mortality in these patients [7]. The incidence of pulmonary hypertension in HD patients ranges from 17 to 60% and is associated with the presence of AVF [3–6]. The leading mechanism underlying pulmonary hypertension development in these patients is the volProf. Massimo Volpe, MD, FAHA, FESC Division of Cardiology, 2nd Faculty of Medicine University of Rome ‘Sapienza’, Sant’Andrea Hospital Via di Grottarossa 1035-9, IT–00189 Rome (Italy) Tel. +39 06 3377 5654, Fax +39 06 3377 5061, E-Mail massimo.volpe @ uniroma1.it
ume/pressure overload imposed by the shunt which increases right ventricular output and pulmonary pressures. On the other hand, AVF determines a chronic increase in preload which may impair right ventricular performance independently of post-load conditions [8]. Moreover, when AVF is placed at the brachial instead of radial level, it may exacerbate right ventricular overload via an increased blood flow through the AVF [4]. Patients undergoing peritoneal dialysis (PD) may also develop pulmonary hypertension, but the magnitude of this abnormality appears to be lower, ranging from 6 to 42% [6, 9]. In this condition an increase in body water amplifies the effects of the predisposing factors leading to pulmonary hypertension in patients with chronic renal failure, as suggested by the observed correlation between hydration status and pulmonary pressure [9]. Although patients undergoing chronic dialysis exhibit an increased prevalence of pulmonary hypertension during treatment, data on the development of right ventricular dysfunction (RVD) are lacking. Moreover, in patients with pulmonary hypertension, survival has been related to cardiac function rather than pulmonary pressure values [10]. Importantly, RVD may also affect left ventricular filling via interventricular interaction [8]. In recent years, the assessment of right ventricular function by tissue Doppler imaging (TDI) has been established as a common approach to detect preclinical abnormalities of cardiac function and has also been proposed as a reliable predictor of prognosis [11]. Previous works regarding the relation between pulmonary hypertension and dialysis have mostly investigated the impact of volume overload on TDI indices of left ventricular function, showing an increased prevalence of diastolic dysfunction in these patients [12, 13]. However, data on the prevalence of RVD in patients undergoing chronic dialysis are still lacking. This study was designed to investigate the impact of chronic dialysis therapy on right ventricular function. Among patients receiving HD, we also assessed the impact of AVF placement, either brachial or radial, on the development of RVD. Methods Selection of Patients The study population consisted of 120 patients with end-stage renal disease on a regular dialysis program and 100 healthy subjects (mean age 54.9 8 12.7 years, male/female: 144/76). Patients with end-stage renal disease were admitted at the Division of Nephrology of the Sant’Andrea Hospital in Rome. Patients undergoing dialysis were grouped as follows: 26 patients on PD, 62 HD patients with radial and 32 with brachial AVF.
Right Ventricular Dysfunction in Dialysis Patients
Patients undergoing HD had been on maintenance therapy for at least 1 month and were receiving HD sessions 3 times per week. Each session lasted for 4 h and used bicarbonate-buffered dialysate. Standard Kt/V was calculated as previously reported [14]. Every participant gave their informed consent and all the diagnostic procedures were approved by our institute’s ethics committee. All patients underwent full clinical evaluation to rule out any clinical condition that might predispose to pulmonary hypertension (chronic obstructive pulmonary disease, interstitial pneumopathy, connective tissue disorders, chronic thromboembolic disease, congenital left-to-right shunts, primary pulmonary hypertension). They also underwent chest X-rays, standard 12-lead electrocardiography and arterial blood gas analysis. The exclusion criteria were defined by clinical or echocardiographic evidence of ischemic heart disease, left ventricular dysfunction, valvulopathy or previous renal transplantation. Echocardiography All study patients underwent transthoracic echocardiography, including both conventional and TDI of the left and the right ventricle. Echocardiography was performed within 1 h after the completion of HD while the patients were at optimal dry weight to avoid any overestimation of pulmonary pressure due to volume overload. Two-dimensional and M-mode evaluation was performed using an Acuson Sequoia쏐 C 256 ultrasound machine. All examinations were supervised online by an expert sonographer (G.M.C). Left ventricular diameters and wall thickness were measured according to the American Society of Echocardiography [15]. Left ventricular volumes were estimated using the z-derived method [16]. Ejection fraction of the left ventricle was calculated using the Teicholz formula and further confirmed with Simpson’s technique in the 4-chamber view. Pulsed-wave Doppler of mitral inflow velocity was performed as previously described [17]. The maximal tricuspid regurgitation velocity was measured by continuous wave Doppler echocardiography from the apical 4-chamber view. The highest peak velocity was recorded and the average peak velocities from 3 beats were calculated. Systolic pulmonary pressure was calculated as follows: 4 ! (tricuspid systolic jet)2 + right atrial pressure. Pulmonary hypertension was defined as a value of systolic pulmonary pressure 135 mm Hg at rest. Right ventricular diameters were measured in the long axis view. Ejection fraction of the right ventricle was calculated by using the Simpson’s formula from the apical 4-chamber view [18]. Early (E) and late (A) right ventricular inflow velocities were measured with pulse-wave Doppler by placing the sample volume in between the tips of the tricuspid valve in the apical 4-chamber window. The TDI spectral signal was acquired from the apical 4-chamber view, with the sample volume placed along the lateral and septal tricuspid annulus [19]. Sm (systolic myocardial velocity), Em (protodiastolic myocardial velocity) and late peak diastolic myocardial velocity (Am) were measured. The E/Em ratio, an index of ventricular filling pressure, was calculated [17]. Ejection time, isovolumic relaxation time and isovolumic contraction time were also measured. Regional TDI myocardial performance index (MPI) was calculated as previously reported [20]. Average regional TDI MPI for the right ventricle was calculated as follows: (MPIlateral + MPIseptal)/2 [19]. RVD was defined by an average regional MPI value 12 SD from the mean of the values derived from a group of 100 healthy subjects (MPI 1 0.53).
Am J Nephrol 2010;32:432–438
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Table 1. Characteristics of the study population
Age, years Gender, M:F BMI HR, beats/min SBP, mm Hg DBP, mm Hg Duration of dialysis, months Hypertension, % Diabetes, % Antihypertensive medications, % ACE-inhibitors, % ARBs, % -Blockers, % CCB, % Diuretics, % Others, % Erythropoietin, %
Controls (n = 100)
PD (n = 26)
HD (n = 94)
p
radial AVF (n = 62)
brachial AVF (n = 32)
52.889.5 69:31 25.484.1 67.9810.6 125.9816.6 77.7811.7 – – – – – – – – – – –
52.2815.2 13:13 24.184.0 75.5812.6* 132.8811.5 82.189.3 37833 65.4 23.1 69.2 23.1 19.2 30.8 34.6 34.6 26.9 84.6
57.3814.1 41:21 26.085.8 76.0812.5* 130.0824.5 76.6813.8 44829 54.8 27.4 61.3 16.1 4.8 32.3 33.9 25.8 21.0 83.9
58.8814.3 21:11 25.684.9 77.9812.9* 130.0817.0 81.1812.2 45827 56.3 21.9 56.3 28.1 15.6 37.5 34.4 31.3 18.8 78.1
0.11 0.34 0.86
