Sudden Cardiac Death In Hemodialysis Patients Research Articles

The Contribution of Known Familial Cardiovascular Disease Genes to Sudden Cardiac Death in Patients Undergoing Hemodialysis

Introduction: Patients with chronic kidney disease experience high rates of cardiovascular mortality and morbidity. When kidney disease progresses to the need for dialysis, sudden cardiac death (SCD) accounts for 25–35% of all cardiovascular deaths. The objective was to determine if rare genetic variants known to be associated with cardiovascular death in the general population are associated with SCD in patients undergoing hemodialysis. Methods: We performed a case-control study comparing 126 (37 African American [AfAn] and 89 European ancestry [EA]) SCD subjects and 107 controls (34 AfAn and 73 EA), matched for age, sex, self-reported race, dialysis duration (<2, 2–5 and >5 years), and the presence or absence of diabetes mellitus. To target the coding regions of genes previously reported to be associated with 15 inherited cardiac conditions (ICCs), we used the TruSight Cardio Kit (Illumina, San Diego, CA, USA) to capture the genetic regions of interest. In all, the kit targets 572-kb regions that include the protein-coding regions and 40-bp 5′ and 3′ end-flanking regions of 174 genes associated with the 15 ICCs. Using the sequence data, burden tests were conducted to identify genes with an increased number of variants among SCD cases compared to matched controls. Results: Eleven genes were associated with SCD, but after correction for multiple testing, none of the 174 genes were identified as having more variants in the SCD cases than the matched controls, including previously identified genes. Secondary burden tests grouping variants based on diseases and gene function did not produce statistically significant associations. Discussion/Conclusions: We found no associations between genes known to be associated with ICCs and SCD in our sample of patients undergoing hemodialysis. This suggests that genetic causes are unlikely to be a major pathogenic factor in SCD in hemodialysis patients, although our sample size limits definitive conclusions.

Changes in QTc interval in long-term hemodialysis patients.

BackgroundCardiovascular diseases, including sudden cardiac death (SCD), are the leading cause of death in hemodialysis (HD) patients. A prolonged QT interval on the electrocardiogram (ECG) is a risk factor for SCD in HD patients. This study investigated whether the heart rate-corrected QT (QTc) interval becomes prolonged along with dialysis vintage.MethodsA total of 102 HD patients were retrospectively studied. Their ECG data were analyzed at 1, 4, and 7 years after HD initiation. The control group comprised 68 age-matched individuals who had normal renal function and two available ECG reports at an interval of more than 4 years. QTc was measured according to the Bazett formula. The association between QTc interval and dialysis vintage was studied. Additionally, clinically relevant variables related to QTc duration at 1 year after HD initiation were assessed.ResultsAverage QTc interval at 4 and 7 years after HD initiation was significantly longer than that at 1 year after HD initiation (443, 445, and 437 ms) (p<0.05). On the other hand, QTc interval in the control group was 425 ms in the first year and 426 ms after an average of 6 years. They had no significant differences, although they were much shorter than that in HD patients. Multivariate regression analysis of baseline variables revealed that the corrected calcium levels (p = 0.041) and diabetes (p = 0.043) were independently associated with longer QTc interval.ConclusionsThe QTc interval at 1 year after HD initiation was longer than in the control subjects and was prolonged over several years of HD treatment. Providing clinical management with a focus on QTc interval may be helpful for reducing the incidence of SCD in HD patients.

Current Perspectives on Sudden Cardiac Death in Hemodialysis Patients.

Recent lines of evidence suggest that, as in other countries, sudden cardiac death (SCD) is more common in the Japanese dialysis clinical setting than we previously thought. Three specific important findings may underlie the increased incidence of SCD in dialysis patients. Even after successful coronary revascularization, hemodialysis (HD) patients continue to have a higher incidence of SCD than the general population. Second, about 70% or more of end-stage kidney disease patients have concentric and eccentric left ventricular hypertrophy, which predisposes many dialysis patients to interstitial fibrosis, decreased coronary perfusion reserve, and decreased ischemia tolerance. Third, mildly impaired left ventricular dysfunction, with an ejection fraction <50%, is associated with a greater risk of SCD in dialysis patients. We have believed and accepted a common sense theory that paroxysmal ventricular tachycardia and fibrillation are the central cause of SCD in HD patients, because such cardiac functional morphological abnormalities were observed, and there are many chances for ventricular arrhythmia triggers, such as volume expansion and electrolyte shift, to develop. However, the type of fatal arrhythmia responsible for SCD differs between before and after HD. Sudden cardiac arrest (SCA) from ventricular fibrillation (VF) was more often seen in the post-HD setting, while SCA from non-VF, which may be bradyarrhythmia, was more often seen in the pre-HD setting. This may imply that the causes of SCA are bradyarrhythmia due to hyperkalemia in the pre-HD setting on the day after a long interval, and fatal ventricular arrhythmia due to a prolonged QT interval in the post-HD setting, because some recent evidence suggests that shifts of electrolytes, such as potassium and calcium, during HD cause rapid prolongation of the QT interval after HD, which may lead to the onset of ventricular arrhythmia and SCD. In fact, a higher calcium gradient, defined as the difference between the pre-HD corrected total serum calcium level and the dialysate calcium level, was associated with a higher risk of SCD in HD patients. Key Messages: Further study is needed to determine which combination of calcium, potassium, and bicarbonate concentrations in dialysate is optimal to avoid SCD in high-risk HD patients.

Association of NTproBNP and cTnI with outpatient sudden cardiac death in hemodialysis patients: the Choices for Healthy Outcomes in Caring for ESRD (CHOICE) study.

BackgroundSudden cardiac death (SCD) is the most common etiology of death in hemodialysis patients but not much is known about its risk factors. The goal of our study was to determine the association and risk prediction of SCD by serum N-terminal prohormone of brain natriuretic peptide (NTproBNP) troponin I (cTnI) in hemodialysis patients.MethodsWe measured NTproBNP and cTnI in 503 hemodialysis patients of a national prospective cohort study. We determined their association with SCD using Cox regression, adjusting for demographics, co-morbidities, and clinical factors and risk prediction using C-statistic and Net Reclassification Improvement (NRI).ResultsPatients’ mean age was 58 years and 54 % were male. During follow-up (median 3.5 years), there were 75 outpatient SCD events. In unadjusted and fully-adjusted models, NTproBNP had a significant association with the risk of SCD. Analyzed as a continuous variable, the risk of SCD increased 27 % with each 2-fold increase in NTproBNP (HR, 1.27 per doubling; 95 % CI, 1.13–1.43; p < 0.001). In categorical models, the risk of SCD was 3-fold higher in the highest tertile of NTproBNP (>7,350 pg/mL) compared with the lowest tertile (<1,710 pg/mL; HR for the highest tertile, 3.03; 95 % CI, 1.56–5.89; p = 0.001). Higher cTnI showed a trend towards increased risk of SCD in fully adjusted models, but was not statistically significant (HR, 1.17 per doubling; 95 % CI, 0.98–1.40; p = 0.08). Sensitivity analyses using competing risk models showed similar results. Improvement in risk prediction by adding cardiac biomarkers to conventional risk factors was greater with NTproBNP (C-statistic for 3-year risk: 0.810; 95 % CI, 0.757 to 0.864; and continuous NRI: 0.270; 95 % CI, 0.046 to 0.495) than with cTnI.ConclusionsNTproBNP is associated with the risk of SCD in hemodialysis patients. Further research is needed to determine if biomarkers measurement can guide SCD risk prevention strategies in dialysis patients.Electronic supplementary materialThe online version of this article (doi:10.1186/s12882-016-0230-x) contains supplementary material, which is available to authorized users.

Association between Clinical and Doppler Echocardiographic Parameters with Sudden Death in Hemodialysis Patients.

Background:Sudden cardiac death (SCD) is the leading cause of death in maintenance hemodialysis (HD) patients, but there is little information about underlying risk factors.Objectives:Evaluate the association between clinical and echocardiographic variables with SCD on HD patients.Methods:Retrospective nested case-control study on chronic HD patients who were prospectively followed. The primary endpoint was SCD. Variables were compared by Student t test, Mann-Whitney or Chi-Square, and independent predictors of SCD were evidenced by multivariate logistic regression.Results:We followed 153 patients (50 ± 15 years, 58% men) for 23 ± 14 months and observed 35 deaths, 17 of which were SCD events. When compared to the control group (matched for gender, age, and body mass index) there were no differences regarding time on dialysis, traditional biochemical parameters, blood pressure, smoking, use of cardiovascular protective drugs, ejection fraction, left ventricular dimensions, and diastolic function indices. On the other hand, in the SCD group, we found a higher prevalence of previous heart failure, acute myocardial infarction and diabetes, greater left ventricular mass index, greater left atrial size and lower global myocardial performance. After multivariate logistic regression analysis, diabetes (OR = 2.6; CI = 1.3-7.5; p = 0.023) and left ventricular mass index ≥ 101 g/m2.7 (OR = 1.04; CI = 1.01-1.08; p = 0.028) showed independent association with SCD events.Conclusions:HD patients with diabetes mellitus and left ventricular hypertrophy appear to have the highest risk of SCD. Preventive and therapeutic strategies should be encouraged in addressing these risk factors to minimize the occurrence of SCD in HD patients.

Sudden cardiac death in haemodialysis patients: preventative options.

Sudden cardiac death (SCD) is the most common cause of death in haemodialysis patients, accounting for 25% of all-cause mortality. There are many potential pathological precipitants as most patients with end-stage renal disease have structurally or functionally abnormal hearts. For example, at initiation of dialysis, 74% of patients have left ventricular hypertrophy. The pathophysiological and metabolic milieu of patients with end-stage renal disease, allied to the regular stresses of dialysis, may provide the trigger to a fatal cardiac event. Prevention of SCD can be seen as a legitimate target to improve survival in this patient group. In the general population, this is most effective by reducing the burden of ischaemic heart disease. However, the aetiology of SCD in haemodialysis patients appears to be different, with myocardial fibrosis, vascular calcification and autonomic dysfunction implicated as possible causes. Thus, the range of therapies is different to the general population. There are potential preventative measures emerging as our understanding of the underlying mechanisms progresses. This article aims to review the evidence for therapies to prevent SCD effective in the general population when applied to dialysis patients, as well as promising new treatments specific to this population group.

Sudden cardiac death in haemodialysis patients: Assessment of risk factors and prevention

Haemodialysis patients are at high risk for sudden cardiac death (SCD), with the annual mortality rate from SCD ranging from 5-7%. The risk factors for SCD on haemodialysis include left ventricular remodelling, coronary disease, heart failure, rapid electrolyte and fluid shifts during dialysis sessions and secondary hyperparathyroidism. Echocardiography and standard electrocardiography can help identify patients at risk for SCD. The strategy for preventing SCD in haemodialysis patients includes primary (medicamentous treatment and adjusting dialysis parameters) and secondary (coronary revascularisation and placement of cardioverter defibrillator) treatment planning.