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      Development and Validation of a Deep-Learning Model to Screen for Hyperkalemia From the Electrocardiogram

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          Abstract

          Can a deep-learning model classify hyperkalemia from the electrocardiogram (ECG) in patients with chronic kidney disease? In this validation study, a deep neural network was trained using more than 1.5 million ECGs recorded from 1994 to 2017 from approximately 450 000 patients seen at the Mayo Clinic in Minnesota and validated on nearly 62 000 ECGs from the Mayo Clinic in Minnesota, Florida, and Arizona. Using 2 or 4 ECG leads, a deep-learning model detected hyperkalemia with high sensitivity and negative predictive value, with an area under the curve between 0.853 and 0.901. Deep learning may enable noninvasive screening for hyperkalemia in at-risk patients with chronic kidney disease. For patients with chronic kidney disease (CKD), hyperkalemia is common, associated with fatal arrhythmias, and often asymptomatic, while guideline-directed monitoring of serum potassium is underused. A deep-learning model that enables noninvasive hyperkalemia screening from the electrocardiogram (ECG) may improve detection of this life-threatening condition. To evaluate the performance of a deep-learning model in detection of hyperkalemia from the ECG in patients with CKD. A deep convolutional neural network (DNN) was trained using 1 576 581 ECGs from 449 380 patients seen at Mayo Clinic, Rochester, Minnesota, from 1994 to 2017. The DNN was trained using 2 (leads I and II) or 4 (leads I, II, V3, and V5) ECG leads to detect serum potassium levels of 5.5 mEq/L or less (to convert to millimoles per liter, multiply by 1) and was validated using retrospective data from the Mayo Clinic in Minnesota, Florida, and Arizona. The validation included 61 965 patients with stage 3 or greater CKD. Each patient had a serum potassium count drawn within 4 hours after their ECG was recorded. Data were analyzed between April 12, 2018, and June 25, 2018. Use of a deep-learning model. Area under the receiver operating characteristic curve (AUC) and sensitivity and specificity, with serum potassium level as the reference standard. The model was evaluated at 2 operating points, 1 for equal specificity and sensitivity and another for high (90%) sensitivity. Of the total 1 638 546 ECGs, 908 000 (55%) were from men. The prevalence of hyperkalemia in the 3 validation data sets ranged from 2.6% (n = 1282 of 50 099; Minnesota) to 4.8% (n = 287 of 6011; Florida). Using ECG leads I and II, the AUC of the deep-learning model was 0.883 (95% CI, 0.873-0.893) for Minnesota, 0.860 (95% CI, 0.837-0.883) for Florida, and 0.853 (95% CI, 0.830-0.877) for Arizona. Using a 90% sensitivity operating point, the sensitivity was 90.2% (95% CI, 88.4%-91.7%) and specificity was 63.2% (95% CI, 62.7%-63.6%) for Minnesota; the sensitivity was 91.3% (95% CI, 87.4%-94.3%) and specificity was 54.7% (95% CI, 53.4%-56.0%) for Florida; and the sensitivity was 88.9% (95% CI, 84.5%-92.4%) and specificity was 55.0% (95% CI, 53.7%-56.3%) for Arizona. In this study, using only 2 ECG leads, a deep-learning model detected hyperkalemia in patients with renal disease with an AUC of 0.853 to 0.883. The application of artificial intelligence to the ECG may enable screening for hyperkalemia. Prospective studies are warranted. This validation study evaluates the performance of a deep-learning model in detection of hyperkalemia from the electrocardiogram in patients with chronic kidney disease.

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          Most cited references16

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          Rates of hyperkalemia after publication of the Randomized Aldactone Evaluation Study.

          The Randomized Aldactone Evaluation Study (RALES) demonstrated that spironolactone significantly improves outcomes in patients with severe heart failure. Use of angiotensin-converting-enzyme (ACE) inhibitors is also indicated in these patients. However, life-threatening hyperkalemia can occur when these drugs are used together. We conducted a population-based time-series analysis to examine trends in the rate of spironolactone prescriptions and the rate of hospitalization for hyperkalemia in ambulatory patients before and after the publication of RALES. We linked prescription-claims data and hospital-admission records for more than 1.3 million adults 66 years of age or older in Ontario, Canada, for the period from 1994 through 2001. Among patients treated with ACE inhibitors who had recently been hospitalized for heart failure, the spironolactone-prescription rate was 34 per 1000 patients in 1994, and it increased immediately after the publication of RALES, to 149 per 1000 patients by late 2001 (P<0.001). The rate of hospitalization for hyperkalemia rose from 2.4 per 1000 patients in 1994 to 11.0 per 1000 patients in 2001 (P<0.001), and the associated mortality rose from 0.3 per 1000 to 2.0 per 1000 patients (P<0.001). As compared with expected numbers of events, there were 560 (95 percent confidence interval, 285 to 754) additional hyperkalemia-related hospitalizations and 73 (95 percent confidence interval, 27 to 120) additional hospital deaths during 2001 among older patients with heart failure who were treated with ACE inhibitors in Ontario. Publication of RALES was not associated with significant decreases in the rates of readmission for heart failure or death from all causes. The publication of RALES was associated with abrupt increases in the rate of prescriptions for spironolactone and in hyperkalemia-associated morbidity and mortality. Closer laboratory monitoring and more judicious use of spironolactone may reduce the occurrence of this complication. Copyright 2004 Massachusetts Medical Society
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            Patiromer in patients with kidney disease and hyperkalemia receiving RAAS inhibitors.

            Hyperkalemia increases the risk of death and limits the use of inhibitors of the renin-angiotensin-aldosterone system (RAAS) in high-risk patients. We assessed the safety and efficacy of patiromer, a nonabsorbed potassium binder, in a multicenter, prospective trial.
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              The frequency of hyperkalemia and its significance in chronic kidney disease.

              Hyperkalemia is a potential threat to patient safety in chronic kidney disease (CKD). This study determined the incidence of hyperkalemia in CKD and whether it is associated with excess mortality. This retrospective analysis of a national cohort comprised 2 103 422 records from 245 808 veterans with at least 1 hospitalization and at least 1 inpatient or outpatient serum potassium record during the fiscal year 2005. Chronic kidney disease and treatment with angiotensin-converting enzyme inhibitors and/or angiotensin II receptor blockers (blockers of the renin-angiotensin-aldosterone system [RAAS]) were the key predictors of hyperkalemia. Death within 1 day of a hyperkalemic event was the principal outcome. Of the 66 259 hyperkalemic events (3.2% of records), more occurred as inpatient events (n = 34 937 [52.7%]) than as outpatient events (n = 31 322 [47.3%]). The adjusted rate of hyperkalemia was higher in patients with CKD than in those without CKD among individuals treated with RAAS blockers (7.67 vs 2.30 per 100 patient-months; P or=5.5 and or=6.0 mEq/L) hyperkalemic event was highest with no CKD (OR, 10.32 and 31.64, respectively) vs stage 3 (OR, 5.35 and 19.52, respectively), stage 4 (OR, 5.73 and 11.56, respectively), or stage 5 (OR, 2.31 and 8.02, respectively) CKD, with all P < .001 vs normokalemia and no CKD. The risk of hyperkalemia is increased with CKD, and its occurrence increases the odds of mortality within 1 day of the event. These findings underscore the importance of this metabolic disturbance as a threat to patient safety in CKD.
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                Author and article information

                Journal
                JAMA Cardiology
                JAMA Cardiol
                American Medical Association (AMA)
                2380-6583
                April 03 2019
                Affiliations
                [1 ]AliveCor Inc, Mountain View, California
                [2 ]Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota
                [3 ]Department of Health Sciences Research, Mayo Clinic, Jacksonville, Florida
                [4 ]Division of Nephrology and Hypertension, Mayo Clinic, Rochester, Minnesota
                Article
                10.1001/jamacardio.2019.0640
                6537816
                30942845
                3e874464-3347-4518-91e4-cc3bbdae2650
                © 2019
                History

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