Portal de Periódicos da CAPES

Atrial fibrillation in end-stage renal disease: an emerging problem

2009; Elsevier BV; Volume: 76; Issue: 3 Linguagem: Inglês

10.1038/ki.2009.144

1523-1755

Panagiotis Korantzopoulos, John Goudevenos,

Cardiac pacing and defibrillation studies

End-stage renal disease is associated with considerable cardiovascular morbidity and mortality. Atrial fibrillation (AF) is prevalent among dialysis patients and adversely affects the clinical outcome. Vazquez et al. report an increased prevalence and incidence of AF in patients who commence dialysis, and an independent association between arrhythmia and mortality risk. Moreover, they examined clinical and laboratory parameters associated with AF. This population study may fuel research aiming at the development of novel preventive and treatment strategies. End-stage renal disease is associated with considerable cardiovascular morbidity and mortality. Atrial fibrillation (AF) is prevalent among dialysis patients and adversely affects the clinical outcome. Vazquez et al. report an increased prevalence and incidence of AF in patients who commence dialysis, and an independent association between arrhythmia and mortality risk. Moreover, they examined clinical and laboratory parameters associated with AF. This population study may fuel research aiming at the development of novel preventive and treatment strategies. End-stage renal disease (ESRD) is associated with increased cardiovascular morbidity and mortality, and cardiac disease is the leading cause of death among patients receiving dialysis (42% of all-cause mortality).1.Shik J. Parfrey P.S. The clinical epidemiology of cardiovascular disease in chronic kidney disease.Curr Opin Nephrol Hypertens. 2005; 14: 550-557Crossref PubMed Scopus (31) Google Scholar,2.Remppis A. Ritz E. Cardiac problems in the dialysis patients: beyond coronary disease.Semin Dial. 2008; 21: 319-325Crossref PubMed Scopus (38) Google Scholar In this context, the steady increase in the incidence of ESRD, disproportionate to the prevalence of chronic kidney disease, further feeds the burden of cardiovascular complications. Despite the wealth of evidence regarding atherosclerotic and valvular heart disease in ESRD patients, data on cardiac arrhythmias are limited.2.Remppis A. Ritz E. Cardiac problems in the dialysis patients: beyond coronary disease.Semin Dial. 2008; 21: 319-325Crossref PubMed Scopus (38) Google Scholar,3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar Notably, atrial fibrillation (AF) has recently emerged as a prevalent cardiac arrhythmia independently associated with ESRD.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar AF in the general population represents a frequent arrhythmia responsible for considerable morbidity and mortality because it independently increases the risk of death up to 1.9-fold and that of stroke fivefold. Its prevalence doubles with each decade of age, reaching the level of 9% at the eighth decade of life. Interestingly, recent data point to the markedly higher prevalence of AF in dialysis patients compared with the age-matched general population.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar, 4.Reinecke H. Brand E. Mesters R. et al.Dilemmas in the management of atrial fibrillation in chronic kidney disease.J Am Soc Nephrol. 2009; 20: 705-711Crossref PubMed Scopus (199) Google Scholar, 5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar The prevalence of AF in ESRD patients varies considerably among the reported studies.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar Nevertheless, the most recent data derived from observational studies indicate a prevalence of 13–27% in ESRD patients with a mean age between 60 and 67 years.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar,5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Along the same lines, a recent population-based cohort study showed a strong and graded inverse association between glomerular filtration rate and the prevalence of AF, independent of other vascular risk factors.6.Iguchi Y. Kimura K. Kobayashi K. et al.Relation of atrial fibrillation to glomerular filtration rate.Am J Cardiol. 2008; 102: 1056-1059Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar With respect to the incidence of AF in ESRD patients, only data on chronic dialysis patients have been published. These data indicate an incidence between 1 and 4.1 per 100 patient-years.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar,5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar The marked differences between the prevalence and incidence rates across the studies can be attributed to several factors, such as different ages of the studied populations, and differences in the type and documentation of the recorded AF episodes, as well as in the time on dialysis and the associated risk factors.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar Vazquez et al.7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar (this issue) extend previous observations and report on the prevalence and incidence of AF in a cohort of patients who started dialysis in their center and were followed for a mean period of 2 years. They also examined the total mortality and stroke incidence during this time period. This well-designed observational study investigated for the first time the prevalence and incidence of AF in chronic kidney disease patients who commence dialysis. Apparently, the prevalence of 12.1% is one of the lowest reported in the literature3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar but is consistent with the fact that the patients were not on chronic dialysis before the initial assessment. On the other hand, the incidence of 5.9 per 100 patient-years is somewhat greater compared with previous data3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar but in keeping with the age of the patients and the regular and strict follow-up, which allowed more accurate and reliable documentation of the arrhythmia.7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar More interestingly, the authors studied the factors associated with AF in this population. In previous studies, several factors have shown an independent association with AF in ESRD.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar These include increasing age, coronary artery disease, left atrial dilatation, right atrial dilatation, duration of dialysis therapy, low performance status as assessed by the Karnofsky index, predialysis systolic blood pressure, and type of dialysis (hemodialysis over peritoneal dialysis).3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar Vazquez et al.7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar mention three risk factors that were independently associated with AF at the start of dialysis, namely female gender, increased left atrial diameter, and age. On the other hand, factors associated with AF development during the follow-up included valvular calcifications, pre-existent bundle branch block, previous stroke, lower left ventricular ejection fraction, increased pulse pressure, and decreased hemoglobin levels. Most of these associations have already been described in previous studies conducted in the general population or in ESRD patients. The presence of valvular calcifications and the presence of anemia may represent indexes of severity of ESRD-associated cardiovascular abnormalities. For example, anemia is a strong predictor of mortality and cardiovascular events in both CKD and heart failure. The predictive value of bundle branch block merits special attention. The intraventricular conduction disturbances often provide a substrate for ventricular dyssynchrony leading to structural and electrophysiological changes that facilitate AF. In future studies it would be interesting to investigate the specific value of each type of bundle branch block as well as the impact of QRS duration. The study by Vazquez et al.7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar not only reinforces the recently described association between ESRD and AF but further supports the unfavorable effect of AF on the survival of these patients.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar, 5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar, 7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar It should be borne in mind that there is a debate as to whether AF is an independent risk factor or simply a cardiovascular risk marker. Remarkably, Genovesi et al. have demonstrated that AF is independently associated with greater mortality in a cohort of long-term hemodialysis patients.5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar However, AF was significantly associated with cardiovascular mortality but not non-cardiovascular death, and it was not related to incident stroke events.5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Moreover, Wiesholzer et al. showed that the presence of AF in hemodialysis patients is not associated with increased stroke risk, and, surprisingly, they found a higher rate of stroke in patients who were on anticoagulation or aspirin.8.Wiesholzer M. Harm F. Tomasec G. et al.Incidence of stroke among chronic hemodialysis patients with nonrheumatic atrial fibrillation.Am J Nephrol. 2001; 21: 35-39Crossref PubMed Scopus (101) Google Scholar In the study by Vazquez et al.,7.Vazquez E. Sanchez-Perales C. Garcia-Garcia F. et al.Atrial fibrillation in incident dialysis patients.Kidney Int. 2009; 76: 324-330Abstract Full Text Full Text PDF PubMed Scopus (99) Google Scholar no data on specific-cause mortality are reported, but the authors indicate that the presence of AF implied an almost 10-fold increase in ischemic stroke events. Despite the aforementioned inconsistent results, it seems that the thromboembolic risk in ESRD patients with AF is elevated.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar,4.Reinecke H. Brand E. Mesters R. et al.Dilemmas in the management of atrial fibrillation in chronic kidney disease.J Am Soc Nephrol. 2009; 20: 705-711Crossref PubMed Scopus (199) Google Scholar It has also been demonstrated that the use of warfarin is associated with a lower risk of mortality in ESRD patients after hospitalization for AF.9.Abbott K.C. Trespalacios F.C. Taylor A.J. et al.Atrial fibrillation in chronic dialysis patients in the United States: risk factors for hospitalization and mortality.BMC Nephrol [online]. 2003; 4: 1Crossref PubMed Scopus (31) Google Scholar Along the same lines, it was recently demonstrated that proteinuria and reduced estimated glomerular filtration rate are associated with a higher rate of thromboembolism in patients with nonvalvular AF independent of other stroke risk factors.10.Go A.S. Fang M.C. Udaltsova N. et al.Impact of proteinuria and glomerular filtration rate on risk of thromboembolism in atrial fibrillation: the anticoagulation and risk factors in atrial fibrillation (ATRIA) study.Circulation. 2009; 119: 1363-1369Crossref PubMed Scopus (307) Google Scholar As with any good study, the questions are more important than the answers. First, the specific cause of mortality was not reported. As was mentioned before, the presence of AF may be related more strongly to cardiovascular mortality. It should be recognized that in dialysis patients, sudden cardiac death and heart failure are the prevailing modes of cardiovascular death.2.Remppis A. Ritz E. Cardiac problems in the dialysis patients: beyond coronary disease.Semin Dial. 2008; 21: 319-325Crossref PubMed Scopus (38) Google Scholar Very recently it was demonstrated that sudden death in chronic dialysis patients is highly and independently associated with the presence of AF.11.Genovesi S. Valsecchi M.G. Rossi E. et al.Sudden death and associated factors in a historical cohort of chronic haemodialysis patients.Nephrol Dial Transplant. 2009; (advance online publication, 16 March doi)https://doi.org/10.1093/ndt/gfp104Crossref PubMed Scopus (115) Google Scholar Second, although AF showed an independent association with mortality in multivariate analysis, one cannot exclude the possibility that this simply represents a marker of cardiovascular pathological changes that accompany ESRD, as the study is observational and therefore cause–effect relationships cannot be examined. Also, there are no data on the drug treatment of the patients. Specifically, it would be interesting to examine whether there are differences between AF and no-AF patients regarding agents that potentially affect cardiac remodeling, such as angiotensin system inhibitors, statins, and β-blockers. In fact, Genovesi et al. have shown that the use of angiotensin-converting enzyme inhibitors in hemodialysis patients was related to a lower incidence of new diagnoses of AF.5.Genovesi S. Vincenti A. Rossi E. et al.Atrial fibrillation and morbidity and mortality in a cohort of long-term hemodialysis patients.Am J Kidney Dis. 2008; 51: 255-262Abstract Full Text Full Text PDF PubMed Scopus (153) Google Scholar Another methodological problem, common in many AF studies, is that the exact burden of the arrhythmia cannot be accurately assessed and is actually underestimated. Inevitably, regular follow-up visits, emergency assessment of symptomatic patients, periodic 12-lead electrocardiographic recordings, and 24-h Holter recordings have a low yield of AF detection given that many episodes are brief and asymptomatic. The exact AF burden over long time periods can be reliably assessed only in patients with implanted modern pacemakers and implantable cardioverter defibrilators able to record atrial high-rate episodes. Another issue that needs further clarification in future studies is the relative significance of different types of AF. In the general population it is now well established that paroxysmal AF carries the same risk in terms of morbidity and mortality compared with persistent and permanent AF. Whether there is a similar risk in the setting of ESRD is uncertain. The differences in the underlying etiology and pathophysiology may imply different effects on morbidity and mortality. For instance, the acute changes in electrolyte levels and especially the relative hypokalemia have been associated with brief paroxysmal AF episodes.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar The pathophysiology of AF in ESRD is complex (Figure 1). It should be recognized that ESRD per se is associated with volume overload and neurohormonal alterations (mainly activation of the sympathetic system and the renin–angiotensin–aldosterone system) that promote ventricular hypertrophy and dilation as well as increased left atrial size and pressure.3.Korantzopoulos P. Kokkoris S. Liu T. et al.Atrial fibrillation in end-stage renal disease.Pacing Clin Electrophysiol. 2007; 30: 1391-1397Crossref PubMed Scopus (36) Google Scholar Inevitably, these abnormalities contribute to the structural and electrical remodeling of the atria. In addition, inflammation and oxidative stress have been implicated in the pathophysiology of ESRD and represent major mechanisms of cardiovascular dysfunction in this setting. Recently, AF has been associated with inflammation and oxidative stress, and much of the current interest regarding pharmacologic therapy has shifted to non-channel-blocking drugs with pleiotropic properties. Whether these interventions have a specific value in ESRD patients is unknown. In conclusion, AF is prevalent among ESRD patients, representing an additional threat in this frail population. Undoubtedly, further larger studies with longer follow-up are needed in order to elucidate the impact of AF on various clinical parameters, as well as the role of different prognostic factors and therapeutic modalities in this setting. Finally, the clarification of the complex underlying pathophysiology may favor the development of effective preventive and treatment strategies. The authors declared no competing interests.