High Oxalate Concentrations Correlate with Increased Risk for Sudden Cardiac Death in Dialysis Patients

Background The clinical significance of accumulating toxic terminal metabolites such as oxalate in kidney failure patients is not well understood. Methods To evaluate serum oxalate concentrations and risk of all-cause mortality and cardiovascular events in a cohort of kidney failure patients requiring chronic dialysis, we performed a post-hoc analysis of the randomized German Diabetes Dialysis Study (4D Study); this study included 1255 European hemodialysis patients with diabetes followed up for a median of 4 years. The results obtained via Cox proportional hazards models were confirmed by competing risk regression and restricted cubic spline modeling in the 4D cohort and validated in a separate cohort of 104 US dialysis patients after a median follow-up of 2.5 years. Results A total of 1108 patients had baseline oxalate measurements, with a median oxalate concentration of 42.4 µM. During follow-up, 548 died, including 139 (25.4%) from sudden cardiac death. A total of 413 patients reached the primary composite cardiovascular endpoint (cardiac death, nonfatal myocardial infarction, and fatal or nonfatal stroke). Patients in the highest oxalate quartile (≥59.7 µM) had a 40% increased risk for cardiovascular events (adjusted hazard ratio [aHR], 1.40; 95% confidence interval [95% CI], 1.08 to 1.81) and a 62% increased risk of sudden cardiac death (aHR, 1.62; 95% CI, 1.03 to 2.56), compared with those in the lowest quartile (≤29.6 µM). The associations remained when accounting for competing risks and with oxalate as a continuous variable. Conclusions Elevated serum oxalate is a novel risk factor for cardiovascular events and sudden cardiac death in dialysis patients. Further studies are warranted to test whether oxalate-lowering strategies improve cardiovascular mortality in dialysis patients.

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Association between digoxin use and sudden cardiac death in individuals with the rs10494366 variant of the NOS1AP gene

European Heart Journal ◽

10.1093/ehjci/ehaa946.3394 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

N Soroush ◽

A Aarnoudse ◽

F Shokri ◽

M Van Den Berg ◽

F Ahmadizar ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Death ◽

Smoking Status ◽

Adaptor Protein ◽

Therapeutic Window ◽

P Value ◽

Qtc Interval ◽

Total Study Population ◽

Increased Risk

Abstract Background Digoxin is one of the oldest cardiovascular medications still used to treat heart failure and atrial fibrillation. Due to its narrow therapeutic window, it is associated with life threatening intoxication and arrhythmias, and with QTc-shortening. Common genetic variation in the nitric oxide synthase-1 adaptor protein (NOS1AP) has been associated with QTc interval prolongation. Purpose We investigated whether the rs10494366 variant of the NOS1AP gene modified the risk of SCD in patients using digoxin. Methods In a prospective population-based cohort study, we included data of the three cohorts, started as of January 1st, 1991 until January 1st 2014. Digoxin current use on the date of cardiac death in cases and the same day of follow-up in the remainder of the cohort was a time-dependent exposure. The main outcome was SCD defined as sudden and unexpected death as a result of cardiac causes, according to international criteria. Identification and adjudication of SCD was performed independently, before the start of this study. We used Cox proportional hazard regression analysis to investigate the associations between NOS1AP rs10494366 variant and incident SCD among digoxin users compared to non-users. Associations were adjusted for age, sex (model 1) in addition to BMI, prevalent diabetes, myocardial infarction, baseline hypertension and smoking status (past, current, never) (model 2). Results We included 14,594 individuals, with a mean age of 65.3 (SD 10.3) years. Almost 59% were female. The cumulative incidence of SCD was 9.5% (609 cases) by the end of follow up. Among them, 98 (16%) individuals were exposed to digoxin at the time of death. In model 1, NOS1AP rs10494366 variant was not associated with SCD in the total study population. However, an interaction term of the gene with the daily dose of digoxin was significantly associated with increased risk of SCD (p-value 0.0001). In model 2, the risk of SCD in current users of digoxin was 4.2 [95% CI 1.3–13.8] for the GG genotype; 2.1 [95% CI 1.1–4.2] for the GT genotype, and 1.5 [95% CI 0.7–3.2] for the TT genotype. Conclusion NOS1AP rs10494366 variant modified the risk of sudden cardiac death in users of digoxin. Our study suggests that individuals with the homozygous minor GG allele have a fourfold increased risk of sudden cardiac death. Funding Acknowledgement Type of funding source: None

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FP625CONTINUOUS ECG MONITORING IN NON-DIABETIC PERITONEAL DIALYSIS PATIENTS MAY IDENTIFY PATIENTS AT INCREASED RISK FOR SUDDEN CARDIAC DEATH

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfz106.fp625 ◽

2019 ◽

Vol 34 (Supplement_1) ◽

Author(s):

Andreea Andronesi ◽

Luminita Iliuta ◽

Bogdan Obrisca ◽

Bogdan Sorohan ◽

Gabriela Lupusoru ◽

...

Keyword(s):

Peritoneal Dialysis ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Ecg Monitoring ◽

Dialysis Patients ◽

Increased Risk

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Prediction of sudden cardiac death in Japanese heart failure patients: international validation of the Seattle Proportional Risk Model

EP Europace ◽

10.1093/europace/euaa002 ◽

2020 ◽

Vol 22 (4) ◽

pp. 588-597

Author(s):

Ryoma Fukuoka ◽

Takashi Kohno ◽

Shun Kohsaka ◽

Yasuyuki Shiraishi ◽

Mitsuaki Sawano ◽

...

Keyword(s):

Heart Failure ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Proportional Hazards Model ◽

Risk Model ◽

Cox Proportional Hazards ◽

Cox Proportional Hazards Model ◽

Calibration Plot ◽

Derivation Cohort ◽

Increased Risk

Abstract Aims Heart failure (HF) is associated with an increased risk of sudden cardiac death (SCD). This study sought to demonstrate the incidence of SCD within a multicentre Japanese registry of HF patients hospitalized for acute decompensation, and externally validate the Seattle Proportional Risk Model (SPRM). Methods and results We consecutively registered 2240 acute HF patients from academic institutions in Tokyo, Japan. The discrimination and calibration of the SPRM were assessed by the c-statistic, Hosmer–Lemeshow statistic, and visual plotting among non-survivors. Patient-level SPRM predictions and implantable cardioverter-defibrillator (ICD) benefit [ICD estimated hazard ratio (HR), derived from the Cox proportional hazards model in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)] was calculated. During the 2-year follow-up, 356 deaths (15.9%) occurred, which included 76 adjudicated SCDs (3.4%) and 280 non-SCDs (12.5%). The SPRM showed acceptable discrimination [c-index = 0.63; 95% confidence interval (CI) 0.56–0.70], similar to that of original SPRM-derivation cohort. The calibration plot showed reasonable conformance. Among HF patients with reduced ejection fraction (EF; < 40%), SPRM showed improved discrimination compared with the ICD eligibility criteria (e.g. New York Heart Association functional Class II–III with EF ≤ 35%): c-index = 0.53 (95% CI 0.42–0.63) vs. 0.65 (95% CI 0.55–0.75) for SPRM. Finally, in the subgroup of 246 patients with both EF ≤ 35% and SPRM-predicted risk of ≥ 42.0% (SCD-HeFT defined ICD benefit threshold), mean ICD estimated HR was 0.70 (30% reduction of all-cause mortality by ICD). Conclusion The cumulative incidence of SCD was 3.4% in Japanese HF registry. The SPRM performed reasonably well in Japanese patients and may aid in improving SCD prediction.

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Association Between Silent Myocardial Infarction and Long‐Term Risk of Sudden Cardiac Death

Journal of the American Heart Association ◽

10.1161/jaha.120.017044 ◽

2021 ◽

Vol 10 (1) ◽

Author(s):

Yun‐Jiu Cheng ◽

Yu‐He Jia ◽

Feng‐Juan Yao ◽

Wei‐Yi Mei ◽

Yuan‐Sheng Zhai ◽

...

Keyword(s):

Myocardial Infarction ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Population Attributable Fraction ◽

Cardiovascular Health Study ◽

Primary Study ◽

Hazard Ratios ◽

Increased Risk ◽

Silent Myocardial Infarction

Background Although silent myocardial infarction (SMI) is prognostically important, the risk of sudden cardiac death (SCD) among patients with incident SMI is not well established. Methods and Results We examined 2 community‐based cohorts: the ARIC (Atherosclerosis Risk in Communities) study (n=13 725) and the CHS (Cardiovascular Health Study) (n=5207). Incident SMI was defined as electrocardiographic evidence of new myocardial infarction during follow‐up visits that was not present at the baseline. The primary study end point was physician‐adjudicated SCD. In the ARIC study, 513 SMIs, 441 clinically recognized myocardial infarctions (CMIs), and 527 SCD events occurred during a median follow‐up of 25.4 years. The multivariable hazard ratios of SMI and CMI for SCD were 5.20 (95% CI, 3.81–7.10) and 3.80 (95% CI, 2.76–5.23), respectively. In the CHS, 1070 SMIs, 632 CMIs, and 526 SCD events occurred during a median follow‐up of 12.1 years. The multivariable hazard ratios of SMI and CMI for SCD were 1.70 (95% CI, 1.32–2.19) and 4.08 (95% CI, 3.29–5.06), respectively. The pooled hazard ratios of SMI and CMI for SCD were 2.65 (2.18–3.23) and 3.99 (3.34–4.77), respectively. The risk of SCD associated with SMI is stronger with White individuals, men, and younger age. The population‐attributable fraction of SCD was 11.1% for SMI, and SMI was associated with an absolute risk increase of 8.9 SCDs per 1000 person‐years. Addition of SMI significantly improved the predictive power for both SCD and non‐SCD. Conclusions Incident SMI is independently associated with an increased risk of SCD in the general population. Additional research should address screening for SMI and the role of standard post–myocardial infarction therapy.

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SO059ASSOCIATION OF ALL-CAUSE MORTALITY WITH PRE-HEMODIALYSIS PULSE PRESSURE IN CHRONIC HEMODIALYSIS PATIENTS

Nephrology Dialysis Transplantation ◽

10.1093/ndt/gfaa139.so059 ◽

2020 ◽

Vol 35 (Supplement_3) ◽

Author(s):

Hanjie Zhang ◽

Alhaji Cherif ◽

Peter Kotanko

Keyword(s):

Pulse Pressure ◽

Nonlinear Effects ◽

Continuous Variable ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Cardiac Insufficiency ◽

Cardiovascular Morbidity And Mortality ◽

Increased Risk ◽

All Cause Mortality

Abstract Background and Aims Chronic and end-stage kidney disease patients experience significantly increased risk of cardiovascular morbidity and mortality due to multitude of interlinked pathophysiological processes inducing metabolic and inflammatory conditions. Pulse pressure (PP) reports cardiac and vascular conditions, where consistently high PP values are associated with atrial fibrillation, aortic insufficiency, arterial stiffness or arteriovenous malformation, and low PP values may be associated with aortic valve stenosis, cardiac insufficiency or cardiac tamponade. However, the association of pre-hemodialysis (pre-HD) PP with mortality among hemodialysis patients is not well understood. In this study, we aim to explore the extent to which PP is associated with mortality. Method We analyzed pre-HD PP (calculated as pre-HD SBP minus pre-HD DBP) between 1/2001 and 12/2012 in hemodialysis patients treated in U.S. Fresenius Medical Care facilities. A 3-months baseline period was defined as months 4 to 6 after hemodialysis initiation, all-cause mortality was noted during follow-up. Only patients who survived baseline were included. Censoring events were renal transplantation, modality change, or study end. We built Cox proportional hazards models with spline terms, allowing us to model nonlinear effects of pre-HD PP as a continuous variable and its relationship with all-cause mortality. Results We included 152,625 patients. Mean age was 60.8 years, 59% were white and 56% were male. During a median follow-up of 26.0 months 40.4% patients died. We found that for patients with pre-HD PP between 49.2 mmHg and 74.7 mmHg, were associated with better survival. In contrast, a PP below 49.2 mmHg and above 74.7 mmHg were associated with higher mortality. Similar nonlinear effects are seen in SBP for a given pre-HD PP value (see Fig. 1). Conclusion The association of pre-HD PP with mortality is nonlinear, and a better understanding of the nonlinearity will provide further insights into disentangling the associated mediators affecting its dynamics. Our findings may aid risk stratification in HD patients.

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Abstract P152: Self-reported Physical Activity And Outcomes In Individuals With Chronic Kidney Disease

Circulation ◽

10.1161/circ.143.suppl_1.p152 ◽

2021 ◽

Vol 143 (Suppl_1) ◽

Author(s):

Jacob Bruinius ◽

Mary Hannan ◽

Jinsong Chen ◽

Julia Brown ◽

Mayank Kansal ◽

...

Keyword(s):

Physical Activity ◽

Lower Risk ◽

Cardiovascular Events ◽

Prospective Observational Study ◽

Proportional Hazards ◽

Vigorous Physical Activity ◽

Cox Proportional Hazards ◽

Physically Active ◽

Increased Risk

Background: In the general population, higher levels of physical activity are associated with lower risk for cardiovascular events and mortality. Although individuals with CKD are less physically active than individuals without CKD and at increased cardiovascular risk, the association between physical activity and outcomes has not been extensively evaluated in this population. Hypothesis: Lower levels of physical activity will be associated with an increased risk for cardiovascular events and mortality. Methods: We used data from 3935 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study, an ongoing multi-center prospective observational study of adults with CKD enrolled between 2003 and 2008. Self-reported physical activity was assessed at study entry using a self-reported survey. We evaluated two predictors: walking pace and moderate-to-vigorous physical activity (MVPA) MET-hours per week. Outcomes included physician-adjudicated myocardial infarction (MI), stroke, congestive heart failure (CHF), and cardiovascular (CV) death. Cox proportional hazards were used to assess the association of physical activity with outcomes. Results: At baseline, mean age was 57.7 years, 45.2% (1777 of 3935) were women, 33.4% (1314 of 3935) had self-reported cardiovascular disease, mean eGFR was 44.9 ml/min/m 2 , 11.7% (459 of 3914) were in the fastest walk pace group (>3 mph) and median MVPA was 39.0 MET-hours per week. During a median follow-up of 8.9 years, the number of events was 477 for MI, 230 stroke, 843 CHF, and 1022 CV deaths. In fully adjusted models, fastest walk pace was associated with lower risk for each outcome. Those in the highest MVPA quartile had lower risk for MI and CV death, but not stroke or CHF, compared to those who were least active ( Table 1 ). Conclusion: In this cohort of adults with CKD, higher physical activity was protective against cardiovascular events and cardiovascular mortality, which may have important implications for clinical practice and the design of future studies.

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Long-term Non-Invasive ECG-based Risk Stratification of Sudden Cardiac Death: Extended 5-year Results

International Cardiovascular Forum Journal ◽

10.17987/icfj.v11i0.393 ◽

2017 ◽

Vol 11 ◽

Author(s):

Elena Okisheva ◽

Dmitry Tsaregorodtsev ◽

Vitaly Sulimov

Keyword(s):

Sudden Cardiac Death ◽

Risk Stratification ◽

Predictive Value ◽

Cardiac Death ◽

Ecg Monitoring ◽

Non Invasive ◽

Increased Risk ◽

All Cause Mortality ◽

High Negative Predictive Value

Objectives: To evaluate predictive value of heart rate turbulence (HRT), deceleration capacity (DC) and microvolt T-wave alternans (mTWA) for risk stratification for sudden cardiac death (SCD) in patients after myocardial infarction (MI) during 60 months of follow-up.Methods: We studied 111 patients after MI occurred > 60 days (27 [9; 84] months) before enrollment (84 men; mean age 64.1±10.5 years). All subjects had 24-hour ambulatory ECG monitoring with HRT, DC and mTWA evaluation. Follow-up period was 60 months; primary endpoint was SCD, secondary endpoint included all non-sudden cardiovascular deaths.Results: During follow-up, we registered 19 cases of SCD and 11 cases of non-sudden cardiovascular deaths (including 7 fatal MI and 3 fatal strokes). DC had high negative predictive value (97.4% for all-cause mortality and 93.7% for SCD). DC values below 4.15 for all-cause mortality and 2.0 for SCD significantly increased risk of all-cause mortality (OR 8.5, 95% CI 2.9 to 24.6, р<0.001) и SCD (OR 9.6, 95% CI 3.2 to 28.5, р<0.001). Combined risk assessment at 12 months revealed that the most significant combination was HRT2 and mTWA100 > 53 mcV, which increased risk both of all-cause mortality (30.7-fold) and SCD (63.3-fold); however, at 60 months this predictive value for SCD decreased (OR = 20.8 (95% CI 2.8 to 114.0), p <0.001).Conclusion: Evaluation of HRT, DC and mTWA during 24-hour ECG monitoring may define the high risk of cardiovascular mortality and SCD in post-MI patients especially during the first 12 months after the baseline examination.

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Telemedicine-based early rule out and followup ECG algorithm for COVID-19 patients

EP Europace ◽

10.1093/europace/euab116.518 ◽

2021 ◽

Vol 23 (Supplement_3) ◽

Author(s):

OE Turan ◽

RY Yilancioglu ◽

C Alak ◽

AA Baskurt ◽

B Hunuk ◽

...

Keyword(s):

Sudden Cardiac Death ◽

Cardiac Death ◽

Retrospective Cohort ◽

Care Group ◽

Ecg Monitoring ◽

Funding Sources ◽

Increased Risk ◽

Rule Out ◽

Funding Acknowledgements

Abstract Funding Acknowledgements Type of funding sources: None. Background Drugs with the potential to prolong QT are used in the treatment of coronavirus 19 (COVID-19) pneumonia. We have developed a telemedicine-based corrected QT (QTc) follow-up algorithm that allows early rule out for follow up. Aims In this study, we investigated the availability and safety of the algorithm. Study design Retrospective cohort Methods Consecutive patients; administered hydroxychloroquine (HCQ) for COVID-19 pneumonia were enrolled into digital ECG recording program which includes QTc follow-up algorithm. Results Patients were classified into three groups as those, excluded promptly from the QTc follow-up based on two consecutive ECG findings (early rule out, n = 92) and those, for whom the follow-up was continued (n = 12) and usual care group (n = 68). Of note, 237 ECG tracings were performed in our algorithm population contrary to standard practice of daily recommended ECG monitoring which could have yielded 975 ECG tracings along with accompanied risks of exposure. This way; we ended in 738 (75.7%) fewer ECG tracings. Sustained ventricular arrhythmia or sudden cardiac death was not observed in the entire patient population. Conclusions It is safe to rely on telemedicine-based early rule out algorithm in COVID-19 patients, receiving hydroxychloroquine treatment. This algorithm abolished the need for further ECG in majority of patients without increased risk during follow up. These algorithms can significantly reduce the healthcare worker exposures by eliminating the need for ECG follow-up promptly. Abstract Figure. Covid-19 Follow up Algorithm

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RESEARCH THE VALUE OF THE COMBINATION OF T WAVE ALTERNANS AND NT-PROBNT IN PREDICTING SUDDEN CARDIAC DEATH

Journal of Medicine and Pharmacy ◽

10.34071/jmp.2012.1.10 ◽

2012 ◽

pp. 74-83

Author(s):

Anh Tien Hoang ◽

Nhat Quang Nguyen

Keyword(s):

Myocardial Infarction ◽

Sudden Cardiac Death ◽

Cardiac Death ◽

Ventricular Arrhythmias ◽

Healthy Person ◽

Treadmill Test ◽

T Wave ◽

T Wave Alternans

Background: Decades of research now link TWA with inducible and spontaneous clinical ventricular arrhythmias. This bench-to-bedside foundation makes TWA, NT-ProBNP a very plausible index of susceptibility to ventricular arrythmia, and motivates the need to define optimal combination of TWA and NT-ProBNP in predicting ventricular arrythmia in myocardial infarction patients. We research this study with 2 targets: 1. To evaluate the role of TWA in predicting sudden cardiac death in myocardial infarction patients. 2. To evaluate the role of NT-ProBNP in predicting sudden cardiac death in myocardial infarction patients 3. Evaluate the role of the combined NT-ProBNP and TWA in predicting sudden cardiac death in myocardial infarction patients. Methods: Prospective study with follow up the mortality in 2 years: 71 chronic myocardial infarction patients admitted to hospital from 5/2009 to 5/20011 and 50 healthy person was done treadmill test to caculate TWA; ECG, echocardiography, NT-ProBNP. Results: Cut-off point of NT-ProBNP in predicting sudden cardiac death is 3168 pg/ml; AUC = 0,86 (95% CI: 0,72 - 0,91); Cut-off point of TWA in predicting sudden cardiac death is 107 µV; AUC = 0,81 (95% CI: 0,69 - 0,87); NT-ProBNP can predict sudden cardiac death with OR= 7,26 (p<0,01); TWA can predict sudden cardiac death with OR= 8,45 (p<0,01). The combined NT-ProBNP and TWA in predicting ventricular arrythmia in heart failure patients: OR= 17,91 (p<0,001). Conclusions: The combined NT-ProBNP and TWA have the best predict value of sudden cardiac death in myocardial infarction patients, compare to NT-ProBNP or TWA alone

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Serum urate and cardiovascular events in the DCCT/EDIC study

Scientific Reports ◽

10.1038/s41598-021-90785-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Alicia J. Jenkins ◽

Barbara H. Braffett ◽

Arpita Basu ◽

Ionut Bebu ◽

Samuel Dagogo-Jack ◽

...

Keyword(s):

Cardiovascular Events ◽

Serum Urate ◽

Continuous Variable ◽

Major Adverse Cardiovascular Events ◽

Normal Range ◽

The Metabolic Syndrome ◽

Routine Measurement

AbstractIn type 2 diabetes, hyperuricemia is associated with cardiovascular disease (CVD) and the metabolic syndrome (MetS), but associations in type 1 diabetes (T1D) have not been well-defined. This study examined the relationships between serum urate (SU) concentrations, clinical and biochemical factors, and subsequent cardiovascular events in a well-characterized cohort of adults with T1D. In 973 participants with T1D in the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Study (DCCT/EDIC), associations were defined between SU, measured once in blood collected 1997–2000, and (a) concurrent MetS and (b) incident ‘any CVD’ and major adverse cardiovascular events (MACE) through 2013. SU was higher in men than women [mean (SD): 4.47 (0.99) vs. 3.39 (0.97) mg/dl, respectively, p < 0.0001], and was associated with MetS features in both (men: p = 0.0016; women: p < 0.0001). During follow-up, 110 participants (11%) experienced “any CVD”, and 53 (5%) a MACE. Analyzed by quartiles, SU was not associated with subsequent CVD or MACE. In women, SU as a continuous variable was associated with MACE (unadjusted HR: 1.52; 95% CI 1.07–2.16; p = 0.0211) even after adjustment for age and HbA1c (HR: 1.47; 95% CI 1.01–2.14; p = 0.0467). Predominantly normal range serum urate concentrations in T1D were higher in men than women and were associated with features of the MetS. In some analyses of women only, SU was associated with subsequent MACE. Routine measurement of SU to assess cardiovascular risk in T1D is not merited.Trial registration clinicaltrials.gov NCT00360815 and NCT00360893.

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