Dialysis-induced segmental wall motion abnormalities, post-dialysis fatigue and cardiovascular mortality: the new Bermuda triangle?

Abstract

Dialysis patients exhibit higher rates of death compared withthe general population [1], with an almost similar increase inthe proportion of cardiovascular (CV) and non-CV deaths[1]; however, the CV mortality risk in patients starting dialy-sis is much higher compared with the general population(unstandardized CV risk—15-fold higher/age-standardizedCV risk—8.8 higher than in matched individuals from thegeneral population) [1] and is not determined by the samerisk factors. Indeed, classical atherosclerotic disease is not themost important and common cause of death in a moderndialysis population. Sudden cardiac death (SCD) [2] andheart failure are the most frequent forms of death in dialysispatients; the overall incidence of these events is much greaterthan the incidence of coronary events [3]. Moreover, the riskpersists after coronary vascularization [4]. Important factorsfor this significant CV morbidity include left ventricular (LV)hypertrophy, electrolyte shifts during haemodialysis (HD),poor volume control [5] and abnormalities in myocardialultra-structure and function, including endothelial dysfunc-tion, interstitial fibrosis, impaired coronary flow reserve anddiminished ischaemia tolerance.One potential important player in the mechanisms behindthis excess mortality is the HD procedure. It is obvious thatthe HD procedure is stressful for the CV system; almost 30%of HD sessions are associated with significant intra-dialytic hy-potension [6]. Intermittent HD treatments may induce globaland segmental myocardial ischaemia [7, 8]. This was suggestedby Selby’s studies using echocardiography [9, 10] and cardiactroponin levels [11] and by Singh et al.[12] using 99Tc-sesta-mibi single-photon emission computed tomography. Confir-mation that an HD session is undeniably capable of inducingregional myocardial ischaemia was provided recently by McIn-tyre et al. [7]. Using intra-dialytic H215O positron emissiontomography and echocardiography, they showed that HDtreatment elicited reversible (LV) regional wall motion ab-normalities (RWMAs) with matched reductions in myocardialblood flow (MBF). Dasselaar et al.[8] reconfirmed 1 year laterthese results in non-diabetic non-cardiac-compromisedpatients. They observed a significant reduction in MBF, earlyduring dialyses that were not accompanied by significant fluidremoval.In the general population, repeated episodes of transientmyocardial ischaemia lead to a spectrum of disease encom-passing myocardial stunning, myocardial hibernation andending in myocardial remodelling and scarring, with irrevers-ible loss of contractile function. Myocardial stunning isdefined as a prolonged LV dysfunction without histologicalsigns of irreversible injury to cardiomyocytes. It occurs eachtime when ischaemia and reperfusion are present: in patientswith coronary artery disease, after percutaneous transluminalcoronary angioplasty, after coronary bypass or cardiac trans-plantation or following resuscitation. Myocardial stunninghas been well described in the general population as a causa-tive mechanism for heart failure [9]. Myocardial hibernationis described also as depressed myocardial contractility, butthe ischaemic myocardium remains viable and the LV dys-function can be partially or completely restored to normality,by improving/restoring blood flow. In pathophysiologicalterms, a severe reduction in coronary flow reserve is commonfor both conditions, and recovery of function is paralleled byrestoration of an adequate coronary flow reserve.The reduction in MBF during HD is associated with myo-cardial remodelling and eventually non-viable myocardiumwith irreversible reduction in LV function. This processbecomes increasingly appreciated as a principal pathophysio-logic contributor to the excess CV mortality in HD patients