Association of Dialysate Bicarbonate with Arrhythmia in the Monitoring in Dialysis (MiD) Study.

BACKGROUND: Sudden death accounts for ∼25% of deaths among maintenance hemodialysis (HD) patients, occurring more frequently on HD days. Higher dialysate bicarbonate (DBIC) may predispose to alkalemia and arrhythmogenesis. METHODS: We conducted a 12-month analysis of session-level data from 66 patients with implantable loop recorders. We fit logistic regression and negative binomial mixed effects regression models to assess the association of DBIC with clinically significant arrhythmia (CSA - ventricular tachycardia ≥115 beats per minute (BPM) for at least 30 seconds, bradycardia ≤40 BPM for at least 6 seconds, or asystole for at least 3 seconds) and reviewer confirmed arrhythmia (RCA - implantable-loop-recorder-identified or patient-marked event for which a manual review of the stored ECG tracing confirmed the presence of atrial fibrillation, supraventricular tachycardia, sinus tachycardia with rate >130 BPM, ventricular tachycardia, asystole, or bradycardia). Models adjusted for age, sex, race, HD vintage, vascular access, and pre-HD serum bicarbonate and additionally for serum and dialysate potassium levels. RESULTS: Mean age was 56 ± 12 years, 70% were male, 53% were Black, and 35% were Asian. Fewer RCA episodes were associated with DBIC >35 than 35 mEq/L (incidence rate ratio [IRR] 0.45 (0.27, 0.75) and aIRR 0.54 (0.30, 0.97)), but the association was not significant when adjusting for serum and dialysate potassium levels (aIRR 0.60 (0.32, 1.11)). Otherwise, no associations between DBIC and arrhythmia were identified. CONCLUSIONS: We observed a lower frequency of RCA with higher DBIC, compared with DBIC of 35 mEql/L, contrary to our original hypothesis, but this association was attenuated in fully adjusted models. Validation of these findings in larger studies is required, with a further need for interventional studies to explore the optimal DBIC concentration.

Real-world data of radiofrequency catheter ablation in paroxysmal atrial fibrillation: Short- and long-term clinical outcomes from the prospective multicenter REAL-AF Registry.

BACKGROUND: The safety and long-term efficacy of radiofrequency (RF) catheter ablation (CA) of paroxysmal atrial fibrillation (PAF) has been well established. Contemporary techniques to optimize ablation delivery, reduce fluoroscopy use, and improve clinical outcomes have been developed. OBJECTIVE: The purpose of this study was to assess the contemporary real-world practice approach and short and long-term outcomes of RF CA for PAF through a prospective multicenter registry. METHODS: Using the REAL-AF (Real-world Experience of Catheter Ablation for the Treatment of Symptomatic Paroxysmal and Persistent Atrial Fibrillation; ClincalTrials.gov Identifier: NCT04088071) Registry, patients undergoing RF CA to treat PAF across 42 high-volume institutions and 79 experienced operators were evaluated. The procedures were performed using zero or reduced fluoroscopy, contact force sensing catheters, wide area circumferential ablation, and ablation index as a guide with a target of 380-420 for posterior and 500-550 for anterior lesions. The primary efficacy outcome was freedom from all-atrial arrhythmia recurrence at 12 months. RESULTS: A total of 2470 patients undergoing CA from January 2018 to December 2022 were included. Mean age was 65.2 ±11.14 years, and 44% were female. Most procedures were performed without fluoroscopy (71.5%), with average procedural and total RF times of 95.4 ± 41.7 minutes and 22.1±11.8 minutes, respectively. At 1-year follow-up, freedom from all-atrial arrhythmias was 81.6% with 89.7% of these patients off antiarrhythmic drugs. No significant difference was identified comparing pulmonary vein isolation vs pulmonary vein isolation plus ablation approaches. The complication rate was 1.9%. CONCLUSION: Refinement of RF CA to treat PAF using contemporary tools, standardized protocols, and electrophysiology laboratory workflows resulted in excellent short- and long-term clinical outcomes.

Arrhythmia and Time of Day in Maintenance Hemodialysis: Secondary Analysis of the Monitoring in Dialysis Study.

Rationale & Objective: The incidence of arrhythmia varies by time of day. How this affects individuals on maintenance dialysis is uncertain. Our objective was to quantify the relationship of arrhythmia with the time of day and timing of dialysis. Study Design: Secondary analysis of the Monitoring in Dialysis study, a multicenter prospective cohort study. Settings & Participants: Loop recorders were implanted for continuous cardiac monitoring in 66 participants on maintenance dialysis with a follow up of 6 months. Exposure: Time of day based on 6-hour intervals. Outcomes: Event rates of clinically significant arrhythmia. Analytical Approach: Negative binomial mixed effects regression models for repeated measures were used to evaluate data from the Monitoring in Dialysis study for differences in diurnal patterns of clinically significant arrhythmia among those with end-stage kidney disease with heart failure and end-stage kidney disease alone. We additionally analyzed rates according to presence of heart failure, time of dialysis shift, and dialysis versus nondialysis day. Results: Rates of clinically significant arrhythmia peaked between 12:00 AM and 5:59 AM and were more than 1.5-fold as frequent during this interval than the rest of the day. In contrast, variations in atrial fibrillation peaked between 6:00 AM and 11:59 AM, but variations across the day were qualitatively small. Clinically significant arrhythmia occurred at numerically higher rate in individuals with end-stage kidney disease and heart failure (5.9 events/mo; 95% CI, 1.3-26.8) than those without heart failure (4.0 events/mo; 95% CI, 0.9-17.9). Although differences in overall rate were not significant, their periodicity was significantly different (P < 0.001), with a peak between 12:00 AM and 6:00 AM with kidney failure alone and between 6:00 AM and 11:59 AM in those with heart failure. Although the overall clinically significant arrhythmia rate was similar in morning compared with evening dialysis shifts (P = 0.43), their periodicity differed with a peak between 12:00 AM and 5:59 AM in those with AM dialysis and a later peak between 6:00 AM and 11:59 AM in those with PM shifts. Limitations: Post hoc analysis, unable to account for unmeasured confounders. Conclusion: Clinically significant arrhythmias showed strong diurnal patterns with a maximal peak between 12:00 AM and 5:59 AM and noon. Although overall arrhythmia rates were similar, the peak rate occurred overnight in individuals without heart failure and during the morning in individuals with heart failure. Further exploration of the influence of circadian rhythm on arrhythmia in the setting of hemodialysis is needed.

Arrhythmias occur with a high frequency in individuals with kidney failure. We sought to understand whether there were diurnal patterns for common types of arrhythmias in individuals with kidney failure. We used continuous rhythm data from 66 individuals on dialysis with implantable loop recorders. We found that clinically significant arrhythmias including bradycardia primarily occur overnight and in the early morning, whereas atrial fibrillation is more evenly distributed during the day.

Association of Bradycardia and Asystole Episodes with Dialytic Parameters: An Analysis of the Monitoring in Dialysis (MiD) Study.

Background: Bradycardia and asystole events are common among patients treated with maintenance hemodialysis. However, triggers of these events in patients on maintenance hemodialysis (HD), particularly during the long interdialytic period when these events cluster, are uncertain. Methods: The Monitoring in Dialysis Study (MiD) enrolled 66 patients on maintenance HD who were implanted with loop recorders and followed for 6 months. We analyzed associations of predialysis laboratory values with clinically significant bradyarrhythmia or asystole (CSBA) during the 12 hours before an HD session. Associations with CSBA were analyzed with mixed-effect models. Adjusted negative binomial mixed-effect regression was used to estimate incidence rate ratios (IRR) for CSBA. We additionally evaluated associations of CSBA at any time during follow-up with time-averaged dialytic and laboratory parameters and associations of peridialytic parameters with occurrence of CSBA from the start of one HD session to the beginning of the next. Results: There were 551 CSBA that occurred in the last 12 hours of the interdialytic interval preceding 100 HD sessions in 12% of patients and 1475 CSBA events in 23% of patients overall. We did not identify significant associations between dialytic parameters or serum electrolytes and CSBA in the last 12 hours of the interdialytic interval in adjusted analyses. Median time-averaged ultrafiltration rate was significantly higher in individuals without CSBA (9.8 versus 8, P=0.04). Use of dialysate sodium concentrations ≤135 (versus 140) mEq/L was associated with a reduced risk of CSBA from the start of one session to the beginning of next. Conclusions: Although a few factors had modest associations with CSBA in some analyses, we did not identify any robust associations of modifiable parameters with CSBA in the MiD Study. Further investigation is needed to understand the high rates of arrhythmia in the hemodialysis population.

Ventricular Tachycardia or Fibrillation Storm in Coronavirus Disease.

Ventricular tachycardia (VT) or ventricular fibrillation (VF) storm associated with severe acute respiratory syndrome coronavirus 2 infection is a potentially fatal complication; the correlation of these 2 disorders, however, has not been well studied. This retrospective case series examined outcomes of 2 patients who were admitted for repeated implantable cardioverter-defibrillator shocks with or without syncope and observed to have VT/VF storms with COVID-19. Mechanisms of VT/VF storms in COVID-19 are multifactorial including myocarditis, systemic inflammation, hyperadrenergic state, hemodynamic instability, hypoxia, acidosis, and proarrhythmic drugs. A higher incidence of VT/VF storm is observed in patients with comorbidities and those requiring critical care, with some studies reporting increased mortality. In our cohort, 1 of the 2 patients succumbed to the complications from COVID-19, and the other patient was discharged to home in stable condition. Monitoring of life-threatening arrhythmias in the setting of COVID-19 may need to be adopted to prevent morbidity and mortality.

Implantable Loop Recorder Monitoring and the Incidence of Previously Unrecognized Atrial Fibrillation in Patients on Hemodialysis.

INTRODUCTION: Atrial fibrillation (AF) is common in patients with kidney failure on hemodialysis (KF-HD). We determined both AF incidence and burden in patients with KF-HD using implantable loop recorder (ILR) monitoring. METHODS: Patients with KF-HD were enrolled and received an ILR. In 6 monitoring months, the incidence of AF events lasting ≥6 minutes was captured. Demographic, clinical, and dialysis characteristics were collected, and associations with incident AF were estimated using negative binomial regression models and expressed as incidence rate ratios and 95% CIs. RESULTS: We enrolled 66 patients with KF-HD (mean age = 56 years, 70% male); 59 (90%) were without previously diagnosed AF. AF lasting ≥6 minutes was detected in 18 of 59 subjects (31%) without previously diagnosed AF and in 5 of 7 subjects (71%) with a previous AF diagnosis. Among the 23 with detected AF, episodes were present on 16% of patient days. Although 14 of 23 patients (61%) had AF on <5% of monitored days, the average duration of AF episodes was <1 hour in 13 of 23 patients (52%). Among patients with AF ≥6 minutes, 19 of 23 (83%) had a CHA2DS2-VASc score ≥2. When investigating individual HD parameters, higher dialysate calcium (>2.5 vs. 2.5 mEq/l: incidence rate ratio = 0.62; 95% CI, 0.48-0.80) was associated with lower AF risk whereas higher dialysate bicarbonate concentrations (>35 vs. 35 mEq/l: incidence rate ratio = 3.18; 95% CI, 1.13-8.94) were associated with higher AF risk. CONCLUSION: New AF was detected in approximately one-third of patients with KF-HD. AF affects a substantial proportion of patient days and may be an underappreciated cause of stroke in KF-HD.

Electrolyte Changes in Contemporary Hemodialysis: A Secondary Analysis of the Monitoring in Dialysis (MiD) Study.

BACKGROUND: There is a paucity of contemporary data examining electrolyte changes during and immediately after hemodialysis (HD), and their relationship with dialysate prescriptions. The present study examines these relationships. METHODS: We analyzed patient- (n=66) and HD session-level pre- and post-dialysis laboratory data (n=1,713) over a six-month period from the Monitoring in Dialysis Study. We fit mixed effects regression models to analyze electrolyte, blood urea nitrogen, creatinine, and albumin levels immediately post-HD, accounting for pre-HD and dialysate prescriptions. In a subset of US patients (n=40), 15-minute post-HD and 30-minute post-HD values were available at one session. Predictive models were fit to estimate electrolyte levels immediately post-HD, accounting for pre-HD concentrations and dialysate prescriptions. RESULTS: Serum bicarbonate, calcium, and albumin increased (mean increase 4.9±0.3 mEq/L, 0.7±0.1 mEq/L, and 0.4±0.03 g/dL, respectively), whereas potassium, magnesium, and phosphorus decreased immediately post-HD (mean -1.2±0.1 mEq/L, -0.3±0.03 mEq/L, and -3.0±0.2 mg/dL, respectively). Hypokalemia and hypophosphatemia were present in 40% of and 67% of immediate post-HD samples, respectively. Dynamic changes were observed in electrolyte concentrations at 15- and 30-minutes post-HD, compared to immediately post-HD. CONCLUSION: We describe the magnitude of post-dialytic changes in serum electrolytes with contemporary HD, reporting a high incidence of electrolyte abnormalities post-HD, and present predictive nomograms relating electrolyte changes immediately post-HD to dialysate prescriptions. Our results may be useful for clinical care and provide insights for future research on dialysate prescriptions.

Intradialytic Hypotension and Cardiac Arrhythmias in Patients Undergoing Maintenance Hemodialysis: Results from the Monitoring in Dialysis Study.

BACKGROUND AND OBJECTIVES: Patients receiving maintenance hemodialysis (HD) have a high incidence of cardiac events, including arrhythmia and sudden death. Intradialytic hypotension (IDH) is a common complication of HD and is associated with development of reduced myocardial perfusion, a potential risk factor for arrhythmia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We analyzed data from the Monitoring in Dialysis study, which used implantable loop recorders to detect and continuously monitor electrocardiographic data from patients on maintenance HD (n=66 from the United States and India) over a 6-month period (n=4720 sessions). Negative binomial mixed effects regression was used to test the association of IDH20 (decline in systolic BP >20 mm Hg from predialysis systolic BP) and IDH0-20 (decline in systolic BP 0-20 mm Hg from predialysis systolic BP) with clinically significant arrhythmia (bradycardia≤40 bpm for ≥6 seconds, asystole≥3 seconds, ventricular tachycardia ≥130 bpm for ≥30 seconds, or patient-marked events) during HD. RESULTS: The median age of participants was 58 (25th-75th percentile, 49-66) years; 70% were male; and 65% were from the United States. IDH occurred in 2251 (48%) of the 4720 HD sessions analyzed, whereas IDH0-20 occurred during 1773 sessions (38%). The number of sessions complicated by least one intradialytic clinically significant arrhythmia was 27 (1.2%) where IDH20 occurred and 15 (0.8%) where IDH0-20 occurred. Participants who experienced IDH20 (versus not) had a nine-fold greater rate of developing an intradialytic clinically significant arrhythmia (incidence rate ratio, 9.4; 95% confidence interval, 3.0 to 29.4), whereas IDH0-20 was associated with a seven-fold higher rate (incidence rate ratio, 7.2; 95% confidence interval, 2.1 to 25.4). CONCLUSIONS: IDH is common in patients on maintenance HD and is associated with a greater risk of developing intradialytic clinically significant arrhythmia.

Relationship between dialytic parameters and reviewer confirmed arrhythmias in hemodialysis patients in the monitoring in dialysis study.

BACKGROUND: Hemodialysis patients have high rates of sudden death, but relationships between serum electrolytes, the dialysis prescription, and intra-dialytic shifts in fluid and electrolyte with arrhythmia are uncertain. METHODS: We analyzed sixty-six hemodialysis patients who underwent loop recorder implantation with continuous electrocardiographic monitoring, weekly to bi-weekly testing of pre- and post-dialysis electrolytes, and detailed capture of dialysis prescription and flow sheet data for 6 months. The incidence rate ratio (IRR) of reviewer confirmed arrhythmias (RCA) during dialysis through 8 h after dialysis and associations with serum chemistries and dialytic parameters were assessed using adjusted, negative-binomial regression. RESULTS: Among 66 individuals with a mean age of 56 years, 12,480 events were detected in 64 (97%) patients. RCA nadired 12-24 h after dialysis and increased during the final 12 h of the inter-dialytic interval through the first 8 h after dialysis. Higher pre-dialysis serum magnesium concentration was associated with lower incidence rate ratio for arrythmia (IRR per 1 mg/dL increase 0.49, 95% CI; 0.25, 0.94), as was dialysate calcium concentration > 2.5 mEq/L vs. 2.5 mEq/L (IRR 0.52, 95% CI: 0.39, 0.70). Neither intradialytic serum potassium nor weight change were significantly associated with RCA rate. However, there was effect modification such that arrhythmia rate was maximal with concurrently high intradialytic volume and potassium removal (Pinteraction = 0.01). CONCLUSIONS: Intra and post-dialytic arrhythmias are common in hemodialysis. Additional studies designed to further elucidate whether modification of the serum magnesium concentration, dialysate calcium concentration, and the extent of intradialytic potassium and fluid removal reduces the risk of per-dialytic arrhythmia are warranted. TRIAL REGISTRATION: Clinicaltrials.gov NCT01779856. Prospectively registered on January 22, 2013.

Primary outcomes of the Monitoring in Dialysis Study indicate that clinically significant arrhythmias are common in hemodialysis patients and related to dialytic cycle.

Sudden death is one of the more frequent causes of death for hemodialysis patients, but the underlying mechanisms, contribution of arrhythmia, and associations with serum chemistries or the dialysis procedure are incompletely understood. To study this, implantable loop recorders were utilized for continuous cardiac rhythm monitoring to detect clinically significant arrhythmias including sustained ventricular tachycardia, bradycardia, asystole, or symptomatic arrhythmias in hemodialysis patients over six months. Serum chemistries were tested pre- and post-dialysis at least weekly. Dialysis procedure data were collected at every session. Associations with clinically significant arrhythmias were assessed using negative binomial regression modeling. Sixty-six patients were implanted and 1678 events were recorded in 44 patients. The majority were bradycardias (1461), with 14 episodes of asystole and only one of sustained ventricular tachycardia. Atrial fibrillation, although not defined as clinically significant arrhythmias, was detected in 41% of patients. With thrice-weekly dialysis, the rate was highest during the first dialysis session of the week and was increased during the last 12 hours of each inter-dialytic interval, particularly the long interval. Among serum and dialytic parameters, only higher pre-dialysis serum sodium and dialysate calcium over 2.5 mEq/L were independently associated with clinically significant arrhythmias. Thus, clinically significant arrhythmias are common in hemodialysis patients, and bradycardia and asystole rather than ventricular tachycardia may be key causes of sudden death in hemodialysis patients. Associations with the temporal pattern of dialysis suggest that modification of current dialysis practices could reduce the incidence of sudden death.

Will imaging assist in the selection of patients with heart failure for an ICD?

Sudden cardiac death remains the leading cause of death in the U.S. A left ventricular ejection fraction (LVEF)<30% to 35% identifies a population of patients at increased risk for sudden cardiac death. Once identified, an implantable cardioverter-defibrillator (ICD) is effective in reducing the occurrence of sudden cardiac death. Yet in a substantial proportion of patients who receive an ICD based on reduced LVEF, the device never delivers therapy. Furthermore, the majority of patients who die suddenly do not qualify for ICD placement under current LVEF-based criteria in the guidelines. This review considers the potential role of cardiac imaging in improving the selection of patients most likely to benefit from an ICD. The presence of myocardial scar and/or unrevascularized myocardial ischemia provides an important substrate for the occurrence of potentially fatal ventricular arrhythmias. The presence of clinical heart failure further increases the risk of ventricular arrhythmia. The sympathetic nervous system provides an important trigger for major arrhythmic events, both through global overactivity and through regional heterogeneity of sympathetic activity. A mismatch of myocardial perfusion and innervation may pose a particularly great risk. Imaging modalities provide unique opportunities to investigate the anatomic and pathophysiologic substrates, as well as the triggering effects of cardiac sympathetic innervation. Combining imaging and electrophysiologic modalities offers promise for improved accuracy in future selection of patients with heart failure for ICD placement.