Publications by authors named "Rajat Deo"

135 Publications

Atherosclerotic Cardiovascular Disease Events in Adults With CKD Taking a Moderate- or High-Intensity Statin: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Kidney Med 2021 Sep-Oct;3(5):722-731.e1. Epub 2021 Jun 19.

Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL.

Rationale & Objective: The 2018 American Heart Association/American College of Cardiology (AHA/ACC) cholesterol guideline uses risk stratification to guide the decision to initiate nonstatin lipid-lowering medication among adults with atherosclerotic cardiovascular disease (CVD). We determined atherosclerotic CVD (ASCVD) event rates among adults with chronic kidney disease (CKD) taking statin therapy within 2018 AHA/ACC cholesterol guideline risk categories.

Study Design: Observational cohort study.

Setting & Participants: Adults with CKD not on dialysis in the Chronic Renal Insufficiency Cohort (CRIC) study who were taking a moderate/high-intensity statin 1 year after enrollment (baseline for the current analysis, n = 1,753).

Exposure: 2018 AHA/ACC cholesterol guideline risk categories: without a history of ASCVD, a history of 1 major ASCVD event and multiple high-risk conditions, and a history of ≥2 major ASCVD events.

Outcome: Adjudicated ASCVD events after the year 1 study visit.

Analytical Approach: We calculated age-sex standardized rates for ASCVD events and age-sex adjusted hazard ratios for ASCVD events accounting for the competing risk of death.

Results: There were 394 ASCVD events over a median follow-up period of 8 years. The ASCVD event rates (with 95% CI) per 1,000 person-years among participants without a history of ASCVD, with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 21.7 (18.4-25.1), 45.0 (37.8-52.3), and 73.3 (53.3-93.4), respectively. Compared with participants without a history of ASCVD, the HR (95% CI) rates for ASCVD events among those with a history of 1 major ASCVD event and multiple high-risk conditions, and with a history of ≥2 major ASCVD events were 1.89 (1.52-2.36) and 2.50 (1.85-3.39), respectively.

Limitations: Data on whether participants were taking a maximally tolerated statin dosage were unavailable.

Conclusions: The 2018 AHA/ACC cholesterol guideline identifies adults with CKD who have very high ASCVD risk despite taking a moderate/high-intensity statin.
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http://dx.doi.org/10.1016/j.xkme.2021.04.008DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8515092PMC
June 2021

Impact of left atrial posterior wall isolation on arrhythmia outcomes in patients with atrial fibrillation undergoing repeat ablation.

Heart Rhythm O2 2021 Oct 17;2(5):489-497. Epub 2021 Jul 17.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: It remains unclear whether additional left atrial posterior wall isolation (LAPWI) beyond pulmonary vein reisolation (PVRI) is beneficial in atrial fibrillation (AF) patients undergoing repeat ablation.

Objective: We sought to assess impact of LAPWI on arrhythmia outcomes in patients undergoing repeat AF ablation.

Methods: All AF patients that underwent repeat ablation between January 2016 and December 2018 were included. Those undergoing PVRI only served as control, whereas those undergoing LAPWI (with or without PVRI) were the study group. Primary endpoint was freedom from atrial arrhythmias (AA) off antiarrhythmic drugs (AADs) at 1 year follow-up. Secondary endpoint was freedom from AA on/off AADs at 1 year follow-up.

Results: One hundred ninety-six patients (61% paroxysmal AF, 39% persistent AF) participated; 93 underwent PVRI and 103 underwent LAPWI±PVRI. Patients in the LAPWI group were older, had more hypertension and persistent AF, and had lower rates of PV reconnection (52.4% vs 100%, < .001). LAPWI was performed empirically in 79.6% and to target triggers in 20.4%. It was accomplished by linear lesions across the LA floor and roof alone in 65% and additional LAPW lesions in 35%. The primary and secondary endpoints were similar between patients undergoing LAPWI and those undergoing PVRI (43.7% vs 69.9%, = .50 and 66% vs 77.4%, = .36, respectively). There was no difference in adverse events between the 2 groups.

Conclusion: LAPWI did not improve freedom from atrial arrhythmias on or off AADs at 1 year beyond PVRI in AF patients undergoing repeat ablation. Differences in patient demographics and AF type may underlie the observed lack of benefit of LAPWI, and further study is warranted.
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http://dx.doi.org/10.1016/j.hroo.2021.07.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8505210PMC
October 2021

Prediction of Incident Atrial Fibrillation in Chronic Kidney Disease: The Chronic Renal Insufficiency Cohort Study.

Clin J Am Soc Nephrol 2021 Jul 12;16(7):1015-1024. Epub 2021 Jul 12.

Kidney Research Institute and Division of Nephrology, University of Washington, Seattle, Washington.

Background And Objectives: Atrial fibrillation (AF) is common in CKD and associated with poor kidney and cardiovascular outcomes. Prediction models developed using novel methods may be useful to identify patients with CKD at highest risk of incident AF. We compared a previously published prediction model with models developed using machine learning methods in a CKD population.

Design, Setting, Participants, & Measurements: We studied 2766 participants in the Chronic Renal Insufficiency Cohort study without prior AF with complete cardiac biomarker (N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T) and clinical data. We evaluated the utility of machine learning methods as well as a previously validated clinical prediction model (Cohorts for Heart and Aging Research in Genomic Epidemiology [CHARGE]-AF, which included 11 predictors, using original and re-estimated coefficients) to predict incident AF. Discriminatory ability of each model was assessed using the ten-fold cross-validated -index; calibration was evaluated graphically and with the Grønnesby and Borgan test.

Results: Mean (SD) age of participants was 57 (11) years, 55% were men, 38% were Black, and mean (SD) eGFR was 45 (15) ml/min per 1.73 m; 259 incident AF events occurred during a median of 8 years of follow-up. The CHARGE-AF prediction equation using original and re-estimated coefficients had indices of 0.67 (95% confidence interval, 0.64 to 0.71) and 0.67 (95% confidence interval, 0.64 to 0.70), respectively. A likelihood-based boosting model using clinical variables only had a index of 0.67 (95% confidence interval, 0.64 to 0.70); adding N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, or both biomarkers improved the index by 0.04, 0.01, and 0.04, respectively. In addition to N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, the final model included age, non-Hispanic Black race/ethnicity, Hispanic race/ethnicity, cardiovascular disease, chronic obstructive pulmonary disease, myocardial infarction, peripheral vascular disease, use of angiotensin-converting enzyme inhibitor/angiotensin receptor blockers, calcium channel blockers, diuretics, height, and weight.

Conclusions: Using machine learning algorithms, a model that included 12 standard clinical variables and cardiac-specific biomarkers N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T had moderate discrimination for incident AF in a CKD population.
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http://dx.doi.org/10.2215/CJN.01060121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425618PMC
July 2021

Optimal surgical approach to left atrioesophageal fistula following catheter radiofrequency ablation.

Ann Thorac Surg 2021 Sep 27. Epub 2021 Sep 27.

Division of Cardiothoracic Surgery, Division of Thoracic Surgery, Division of Electrophysiology, The University of Pennsylvania. Electronic address:

Atrioesophageal fistula (AEF) formation is a rare but formidable complication after catheter radiofrequency ablation (RFA) for atrial fibrillation. We present four patients who underwent urgent primary intracardiac repair of the left atrium via sternotomy with central cardiopulmonary bypass and early aortic cross-clamp, followed by repair of the esophagus. We believe that this approach represents the safest strategy for addressing this morbid and often fatal complication.
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http://dx.doi.org/10.1016/j.athoracsur.2021.08.052DOI Listing
September 2021

Implantable loop recorder for augmenting detection of new-onset atrial fibrillation after typical atrial flutter ablation.

Heart Rhythm O2 2021 Jun 28;2(3):255-261. Epub 2021 Apr 28.

Electrophysiology Section, Division of Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Patients with typical atrial flutter (AFL) undergoing successful cavotricuspid isthmus ablation remain at risk for future development of new-onset atrial fibrillation (AF). Conventional monitoring (CM) techniques have shown AF incidence rates of 18%-50% in these patients.

Objectives: To evaluate whether continuous monitoring using implantable loop recorders (ILRs) would enhance AF detection in this patient population.

Methods: Veteran patients undergoing AFL ablation between 2002 and 2019 who completed at least 6 months of follow-up after the ablation procedure were included. We compared new-onset AF detection between those who underwent CM and those who received ILRs immediately following AFL ablation.

Results: A total of 217 patients (age: 66 ± 9 years; all male) participated. CM was used in 172 (79%) and ILR in 45 (21%) patients. Median follow-up duration after ablation was 4.1 years. Seventy-nine patients (36%) developed new-onset AF, which was detected by CM in 51 and ILR in 28 (30% vs 62%, respectively, < .001). AF detection occurred at 7.7 months (IQR: 4.7-17.5) after AFL ablation in the ILR group vs 41 months (IQR: 23-72) in the CM group ( < .001). Eleven patients (5%) experienced cerebrovascular events (all in the CM group) and only 4 of these patients (36%) were on long-term anticoagulation.

Conclusion: Patients undergoing AFL ablation remain at an increased risk of developing new-onset AF, which is detected sooner and more frequently by ILR than by CM. Improving AF detection may allow optimization of rhythm management strategies and anticoagulation in this patient population.
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http://dx.doi.org/10.1016/j.hroo.2021.04.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8322804PMC
June 2021

Comparative Safety of Dipeptidyl Peptidase-4 Inhibitors and Sudden Cardiac Arrest and Ventricular Arrhythmia: Population-Based Cohort Studies.

Clin Pharmacol Ther 2021 Jul 31. Epub 2021 Jul 31.

Center for Pharmacoepidemiology Research and Training, Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

In vivo studies suggest that arrhythmia risk may be greater with less selective dipeptidyl peptidase-4 inhibitors, but evidence from population-based studies is missing. We aimed to compare saxagliptin, sitagliptin, and linagliptin with regard to risk of sudden cardiac arrest (SCA)/ventricular arrhythmia (VA). We conducted high-dimensional propensity score (hdPS) matched, new-user cohort studies. We analyzed Medicaid and Optum Clinformatics separately. We identified new users of saxagliptin, sitagliptin (both databases), and linagliptin (Optum only). We defined SCA/VA outcomes using emergency department and inpatient diagnoses. We identified and then controlled for confounders via a data-adaptive, hdPS approach. We generated marginal hazard ratios (HRs) via Cox proportional hazards regression using a robust variance estimator while adjusting for calendar year. We identified the following matched comparisons: saxagliptin vs. sitagliptin (23,895 vs. 96,972) in Medicaid, saxagliptin vs. sitagliptin (48,388 vs. 117,383) in Optum, and linagliptin vs. sitagliptin (36,820 vs. 78,701) in Optum. In Medicaid, use of saxagliptin (vs. sitagliptin) was associated with an increased rate of SCA/VA (adjusted HR (aHR), 2.01, 95% confidence interval (CI) 1.24-3.25). However, in Optum data, this finding was not present (aHR, 0.79, 95% CI 0.41-1.51). Further, we found no association between linagliptin (vs. sitagliptin) and SCA/VA (aHR, 0.65, 95% CI 0.36-1.17). We found discordant results regarding the association between SCA/VA with saxagliptin compared with sitagliptin in two independent datasets. It remains unclear whether these findings are due to heterogeneity of treatment effect in the different populations, chance, or unmeasured confounding.
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http://dx.doi.org/10.1002/cpt.2381DOI Listing
July 2021

Time-Updated Changes in Estimated GFR and Proteinuria and Major Adverse Cardiac Events: Findings from the Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2021 May 28. Epub 2021 May 28.

Department of Biostatistics, Epidemiology, and Informatics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA.

Rationale & Objective: Evaluating repeated measures of estimated glomerular filtration rate (eGFR) and urinary protein-creatinine ratio (UPCR) over time may enhance our ability to understand the association between changes in kidney parameters and cardiovascular disease risk.

Study Design: Prospective cohort study.

Setting & Participants: Annual visit data from 2,438 participants in the Chronic Renal Insufficiency Cohort (CRIC).

Exposures: Average and slope of eGFR and UPCR in time-updated, 1-year exposure windows.

Outcomes: Incident heart failure, atherosclerotic cardiovascular disease events, death, and a composite of incident heart failure, atherosclerotic cardiovascular disease events, and death.

Analytical Approach: A landmark analysis, a dynamic approach to survival modeling that leverages longitudinal, iterative profiles of laboratory and clinical information to assess the time-updated 3-year risk of adverse cardiovascular outcomes.

Results: Adjusting for baseline and time-updated covariates, every standard deviation lower mean eGFR (19mL/min/1.73m) and declining slope of eGFR (8mL/min/1.73m per year) were independently associated with higher risks of heart failure (hazard ratios [HRs] of 1.82 [95% CI, 1.39-2.44] and 1.28 [95% CI, 1.12-1.45], respectively) and the composite outcome (HRs of 1.32 [95% CI, 1.11-1.54] and 1.11 [95% CI, 1.03-1.20], respectively). Every standard deviation higher mean UPCR (136mg/g) and increasing UPCR (240mg/g per year) were also independently associated with higher risks of heart failure (HRs of 1.58 [95% CI, 1.28-1.97] and 1.20 [95% CI, 1.10-1.29], respectively) and the composite outcome (HRs of 1.33 [95% CI, 1.17-1.50] and 1.12 [95% CI, 1.06-1.18], respectively).

Limitations: Limited generalizability of annual eGFR and UPCR assessments; several biomarkers for cardiovascular disease risk were not available annually.

Conclusions: Using the landmark approach to account for time-updated patterns of kidney function, average and slope of eGFR and proteinuria were independently associated with 3-year cardiovascular risk. Short-term changes in kidney function provide information about cardiovascular risk incremental to level of kidney function, representing possible opportunities for more effective management of patients with chronic kidney disease.
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http://dx.doi.org/10.1053/j.ajkd.2021.03.021DOI Listing
May 2021

The "Shocking" Reality of ICD Therapies.

J Am Coll Cardiol 2021 May;77(20):2463-2465

Electrophysiology Section, Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

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http://dx.doi.org/10.1016/j.jacc.2021.04.019DOI Listing
May 2021

Sex Differences in Cardiovascular Outcomes in CKD: Findings From the CRIC Study.

Am J Kidney Dis 2021 08 20;78(2):200-209.e1. Epub 2021 Apr 20.

Department of Medicine, University of Illinois at Chicago, Chicago, IL. Electronic address:

Rationale & Objective: Cardiovascular events are less common in women than men in general populations; however, studies in chronic kidney disease (CKD) are less conclusive. We evaluated sex-related differences in cardiovascular events and death in adults with CKD.

Study Design: Prospective cohort study.

Setting & Participants: 1,778 women and 2,161 men enrolled in the Chronic Renal Insufficiency Cohort (CRIC).

Exposure: Sex (women vs men).

Outcome: Atherosclerotic composite outcome (myocardial infarction, stroke, or peripheral artery disease), incident heart failure, cardiovascular death, and all-cause death.

Analytical Approach: Cox proportional hazards regression.

Results: During a median follow-up period of 9.6 years, we observed 698 atherosclerotic events (women, 264; men, 434), 762 heart failure events (women, 331; men, 431), 435 cardiovascular deaths (women, 163; men, 274), and 1,158 deaths from any cause (women, 449; men, 709). In analyses adjusted for sociodemographic, clinical, and metabolic parameters, women had a lower risk of atherosclerotic events (HR, 0.71 [95% CI, 0.57-0.88]), heart failure (HR, 0.76 [95% CI, 0.62-0.93]), cardiovascular death (HR, 0.55 [95% CI, 0.42-0.72]), and death from any cause (HR, 0.58 [95% CI, 0.49-0.69]) compared with men. These associations remained statistically significant after adjusting for cardiac and inflammation biomarkers.

Limitations: Assessment of sex hormones, which may play a role in cardiovascular risk, was not included.

Conclusions: In a large, diverse cohort of adults with CKD, compared with men, women had lower risks of cardiovascular events, cardiovascular mortality, and mortality from any cause. These differences were not explained by measured cardiovascular risk factors.
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http://dx.doi.org/10.1053/j.ajkd.2021.01.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8316276PMC
August 2021

Longitudinal Changes in Prorenin and Renin in the Chronic Renal Insufficiency Cohort.

Am J Nephrol 2021 18;52(2):141-151. Epub 2021 Mar 18.

Division of Nephrology and Hypertension, University of Utah, Salt Lake City, Utah, USA.

Introduction: Prorenin, a precursor of renin, and renin play an important role in regulation of the renin-angiotensin system. More recently, receptor-bound prorenin has been shown to activate intracellular signaling pathways that mediate fibrosis, independent of angiotensin II. Prorenin and renin may thus be of physiologic significance in CKD, but their plasma concentrations have not been well characterized in CKD.

Methods: We evaluated distribution and longitudinal changes of prorenin and renin concentrations in the plasma samples collected at follow-up years 1, 2, 3, and 5 of the Chronic Renal Insufficiency Cohort (CRIC) study, an ongoing longitudinal observational study of 3,939 adults with CKD. Descriptive statistics and multivariable regression of log-transformed values were used to describe cross-sectional and longitudinal variation and associations with participant characteristics.

Results: A total of 3,361 CRIC participants had plasma available for analysis at year 1. The mean age (±standard deviation, SD) was 59 ± 11 years, and the mean estimated glomerular filtration rate (eGFR, ± SD) was 43 ± 17 mL/min per 1.73 m2. Median (interquartile range) values of plasma prorenin and renin at study entry were 4.4 (2.1, 8.8) ng/mL and 2.0 (0.8, 5.9) ng/dL, respectively. Prorenin and renin were positively correlated (Spearman correlation 0.51, p < 0.001) with each other. Women and non-Hispanic blacks had lower prorenin and renin values at year 1. Diabetes, lower eGFR, and use of angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, statins, and diuretics were associated with higher levels. Prorenin and renin decreased by a mean of 2 and 5% per year, respectively. Non-Hispanic black race and eGFR <30 mL/min/1.73 m2 at year 1 predicted a steeper decrease in prorenin and renin over time. In addition, each increase in urinary sodium excretion by 2 SDs at year 1 increased prorenin and renin levels by 4 and 5% per year, respectively.

Discussion/conclusions: The cross-sectional clinical factors associated with prorenin and renin values were similar. Overall, both plasma prorenin and renin concentrations decreased over the years, particularly in those with severe CKD at study entry.
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http://dx.doi.org/10.1159/000514302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8049970PMC
March 2021

Protein carbamylation and chronic kidney disease progression in the Chronic Renal Insufficiency Cohort Study.

Nephrol Dial Transplant 2020 Dec 2. Epub 2020 Dec 2.

Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Background: Protein carbamylation is a post-translational protein modification caused, in part, by exposure to urea's dissociation product cyanate. Carbamylation is linked to cardiovascular outcomes and mortality in dialysis-dependent end-stage kidney disease (ESKD), but its effects in earlier pre-dialysis stages of chronic kidney disease (CKD) are not established.

Methods: We conducted two nested case-control studies within the Chronic Renal Insufficiency Cohort Study. First, we matched 75 cases demonstrating CKD progression [50% estimated glomerular filtration rate (eGFR) reduction or reaching ESKD] to 75 controls (matched on baseline eGFR, 24-h proteinuria, age, sex and race). In the second study, we similarly matched 75 subjects who died during follow-up (cases) to 75 surviving controls. Baseline carbamylated albumin levels (C-Alb, a validated carbamylation assay) were compared between cases and controls in each study.

Results: At baseline, in the CKD progression study, other than blood urea nitrogen (BUN) and smoking status, there were no significant differences in any matched or other parameter. In the mortality group, the only baseline difference was smoking status. Adjusting for baseline differences, the top tertile of C-Alb was associated with an increased risk of CKD progression [odds ratio (OR) = 7.9; 95% confidence interval (CI) 1.9-32.8; P = 0.004] and mortality (OR = 3.4; 95% CI 1.0-11.4; P = 0.05) when compared with the bottom tertile. C-Alb correlated with eGFR but was more strongly correlated with BUN.

Conclusions: Our data suggest that protein carbamylation is a predictor of CKD progression, beyond traditional risks including eGFR and proteinuria. Carbamylation's association with mortality was smaller in this limited sample size.
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http://dx.doi.org/10.1093/ndt/gfaa347DOI Listing
December 2020

Periprocedural Acute Kidney Injury in Patients With Structural Heart Disease Undergoing Catheter Ablation of VT.

JACC Clin Electrophysiol 2021 02 28;7(2):174-186. Epub 2020 Oct 28.

Electrophysiology Section, Cardiovascular Medicine Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA. Electronic address:

Objectives: This study sought to examine the impact of periprocedural acute kidney injury (AKI) in scar-related ventricular tachycardia (VT) patients undergoing radiofrequency catheter ablation (RFCA) on short- and long-term outcomes.

Background: The clinical significance of periprocedural AKI in patients with scar-related VT undergoing RFCA has not been previously investigated.

Methods: This study included 317 consecutive patients with scar-related VT undergoing RFCA (age: 64 ± 13 years, mean left ventricular ejection fraction: 33 ± 13%, 55% ischemic cardiomyopathy). Periprocedural AKI was defined as an absolute increase in creatinine of ≥0.3 mg/dl over 48 h or an increase of >1.5× the baseline values within 1 week post-procedure.

Results: Periprocedural AKI occurred in 31 patients (10%). Independent predictors of AKI included chronic kidney disease (odds ratio [OR]: 3.43; 95% confidence interval [CI]: 1.48 to 7.96; p = 0.004), atrial fibrillation (OR: 2.42; 95% CI: 1.01 to 5.78; p = 0.047), and peri-procedural acute hemodynamic decompensation (OR: 3.98; 95% CI: 1.17 to 13.52; p = 0.003). After a median follow-up of 39 months (interquartile range: 6 to 65 months), 95 patients (30%) died. Periprocedural AKI was associated with increased risk of early mortality (within 30 days; hazard ratio [HR]: 9.91; 95% CI: 2.87 to 34.22; p < 0.001) and late mortality (within 1 year) (HR: 4.57; 95% CI: 2.08 to 10.05; p < 0.001). After multivariable adjustment, AKI remained independently associated with increased risk of early and late mortality (HR: 4.49; 95% CI: 1.1 to 18.36; p = 0.04, and HR: 3.28; 95% CI: 1.43 to 7.49; p = 0.005, respectively).

Conclusions: Periprocedural AKI occurs in 10% of patients undergoing RFCA of scar-related VT and is strongly associated with increased risk of early and late post-procedural mortality.
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http://dx.doi.org/10.1016/j.jacep.2020.08.018DOI Listing
February 2021

Stroke, Timing of Atrial Fibrillation Diagnosis, and Risk of Death.

Neurology 2021 03 3;96(12):e1655-e1662. Epub 2021 Feb 3.

From the Division of Cardiovascular Medicine, Department of Medicine (A.B., Y.B., M.C.H., J.A., D.J.C., N.C., S.D., A.E.E., D.S.F., F.C.G., R.K., J.J.L., D.L., S.N., M.P.R., P.S., R.D.S., G.E.S., F.M., R.D.), and Department of Neurology (S.R.M., S.E.K.), Perelman School of Medicine at the University of Pennsylvania School of Medicine, Philadelphia; Department of Biostatistics (R.K.), University of Washington, Seattle; and Division of Cardiology (P.J.P.), St. Vincent Medical Group, Indianapolis, IN.

Objective: To evaluate the prognosis of patients with ischemic stroke according to the timing of an atrial fibrillation (AF) diagnosis, we created an inception cohort of incident stroke events and compared the risk of death between patients with stroke with (1) sinus rhythm, (2) known AF (KAF), and (3) AF diagnosed after stroke (AFDAS).

Methods: We used the Penn AF Free study to create an inception cohort of patients with incident stroke. Mortality events were identified after linkage with the National Death Index through June 30, 2017. We also evaluated initiation of anticoagulants and antiplatelets across the study duration. Cox proportional hazards models evaluated associations between stroke subtypes and death.

Results: We identified 1,489 individuals who developed an incident ischemic stroke event: 985 did not develop AF at any point during the study period, 215 had KAF before stroke, 160 had AF detected ≤6 months after stroke, and 129 had AF detected >6 months after stroke. After a median follow-up of 4.9 years (interquartile range 1.9-6.8), 686 deaths occurred. The annualized mortality rate was 8.8% in the stroke, no AF group; 12.2% in the KAF group; 15.8% in the AFDAS ≤6 months group; and 12.7% in the AFDAS >6 months group. Patients in the AFDAS ≤6 months group had the highest independent risk of all-cause mortality even after multivariable adjustment for demographics, clinical risk factors, and the use of antithrombotic therapies (hazard ratio 1.62 [1.22-2.14]). Compared to the stroke, no AF group, those with KAF had a higher mortality risk that was rendered nonsignificant after adjustment.

Conclusions: The AFDAS group had the highest risk of death, which was not explained by comorbidities or use of antithrombotic therapies.
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http://dx.doi.org/10.1212/WNL.0000000000011633DOI Listing
March 2021

Prognostic Value of Nonischemic Ringlike Left Ventricular Scar in Patients With Apparently Idiopathic Nonsustained Ventricular Arrhythmias.

Circulation 2021 Apr 6;143(14):1359-1373. Epub 2021 Jan 6.

Cardiac Electrophysiology, Cardiovascular Division (D.M., S.A.C., I.L., A.E., J.J.L., S.D., R.D., F.C.G., D.J.C., D.S.F., F.E.M., P.S.), Hospital of the University of Pennsylvania, Philadelphia.

Background: Left ventricular (LV) scar on late gadolinium enhancement (LGE) cardiac magnetic resonance has been correlated with life-threatening arrhythmic events in patients with apparently idiopathic ventricular arrhythmias (VAs). We investigated the prognostic significance of a specific LV-LGE phenotype characterized by a ringlike pattern of fibrosis.

Methods: A total of 686 patients with apparently idiopathic nonsustained VA underwent contrast-enhanced cardiac magnetic resonance. A ringlike pattern of LV scar was defined as LV subepicardial/midmyocardial LGE involving at least 3 contiguous segments in the same short-axis slice. The end point of the study was time to the composite outcome of all-cause death, resuscitated cardiac arrest because of ventricular fibrillation or hemodynamically unstable ventricular tachycardia and appropriate implantable cardioverter defibrillator therapy.

Results: A total of 28 patients (4%) had a ringlike pattern of scar (group A), 78 (11%) had a non-ringlike pattern (group B), and 580 (85%) had normal cardiac magnetic resonance with no LGE (group C). Group A patients were younger compared with groups B and C (median age, 40 vs 52 vs 45 years; <0.01), more frequently men (96% vs 82% vs 55%; <0.01), with a higher prevalence of family history of sudden cardiac death or cardiomyopathy (39% vs 14% vs 6%; <0.01) and more frequent history of unexplained syncope (18% vs 9% vs 3%; <0.01). All patients in group A showed VA with a right bundle-branch block morphology versus 69% in group B and 21% in group C (<0.01). Multifocal VAs were observed in 46% of group A patients compared with 26% of group B and 4% of group C (<0.01). After a median follow-up of 61 months (range, 34-84 months), the composite outcome occurred in 14 patients (50.0%) in group A versus 15 (19.0%) in group B and 2 (0.3%) in group C (<0.01). After multivariable adjustment, the presence of LGE with ringlike pattern remained independently associated with increased risk of the composite end point (hazard ratio, 68.98 [95% CI, 14.67-324.39], <0.01).

Conclusions: In patients with apparently idiopathic nonsustained VA, nonischemic LV scar with a ringlike pattern is associated with malignant arrhythmic events.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.047640DOI Listing
April 2021

Continuous rhythm monitoring-guided anticoagulation after atrial fibrillation ablation.

J Cardiovasc Electrophysiol 2021 02 9;32(2):345-353. Epub 2021 Jan 9.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: Oral anticoagulation (OAC) based on estimated stroke risk is recommended following catheter ablation (CA) of atrial fibrillation (AF), regardless of the extent of arrhythmia control. However, discontinuing OAC in selected patients may be safe. We sought to evaluate a strategy of OAC discontinuation following AF ablation guided by continuous rhythm monitoring.

Methods And Results: We prospectively studied AF ablations performed at our institution from June 2015 to December 2019. Patients that had pre-existing cardiac implantable electronic devices (CIEDs) or underwent insertable cardiac monitor (ICM) implantation immediately following AF ablation were included. OAC was continued for 6 weeks following CA in all patients, following which OAC management was guided by CHA DS -VASc score and continuous rhythm monitoring results, according to a prespecified protocol. AF recurrence was defined as ≥30 s (CIEDs) or ≥2 min (ICM). We studied 196 patients (mean age 64.7 ± 11.3 years, 66.8% male, 85.7% ICM, 14.3% CIEDs). Mean CHA DS VASc score was 2.2  ± 1.5. One-year AF-free survival following CA was 83% for paroxysmal AF and 63% for persistent AF patients. Over 3 year follow-up, OAC was discontinued in 57 (33.7%) patients, mean 7.4 ± 7.1 months following ablation. Following discontinuation, OAC was restarted for AF recurrence in 9 (15.8%) patients, mean 11.7 ± 6.8 months after stopping. This discontinuation protocol led to a 21.9% reduction in overall time exposed to OAC. There were no thromboembolic or major bleeding events.

Conclusion: OAC can be discontinued in a significant percentage of patients following CA of AF. When guided by continuous rhythm monitoring, this practice does not unacceptably increase the risk of thromboembolic events.
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http://dx.doi.org/10.1111/jce.14864DOI Listing
February 2021

Association of circulating cardiac biomarkers with electrocardiographic abnormalities in chronic kidney disease.

Nephrol Dial Transplant 2020 Dec 26. Epub 2020 Dec 26.

Division of Nephrology, Kidney Research Institute, University of Washington, Seattle, WA, USA.

Background: Among patients with chronic kidney disease (CKD), the circulating cardiac biomarkers soluble ST2 (SST2), galectin-3, growth differentiation factor-15 (GDF-15), N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity troponin-T (hsTnT) possibly reflect pathophysiologic processes and are associated with clinical cardiovascular disease. Whether these biomarkers are associated with electrocardiographic findings is not known. The aim of this study was to test the association between serum cardiac biomarkers and the presence of electrocardiographic changes potentially indicative of subclinical myocardial disease in patients with CKD.

Methods: We performed a cross-sectional analysis using 3048 participants from the Chronic Renal Insufficiency Cohort (CRIC) without atrial fibrillation, atrioventricular block, bundle branch block or a pacemaker at the baseline visit. Using logistic regression, we tested the association of each of the five cardiac biomarkers with baseline electrocardiogram (ECG) findings: PR interval >200 ms, QRS interval >100 ms and a prolonged QTc interval. Models were adjusted for demographic variables, measures of kidney function, prevalent cardiovascular disease and cardiovascular risk factors.

Results: In adjusted models, hsTnT levels associated with prolonged PR {odds ratio [OR] 1.23 [95% confidence interval (CI) 1.08-1.40]}, QRS [OR 1.28 (95% CI 1.16-1.42)] and QTc [OR 1.94 (95% CI 1.50-2.51)] intervals. NT-proBNP levels were associated with prolonged QRS [OR 1.11 (95% CI 1.06-1.16)] and QTc [OR 1.82 (95% CI 1.58-2.10)] intervals. SST2, galectin-3 and GDF-15 were not significantly associated with any of the ECG parameters.

Conclusions: hsTnT and NT-proBNP were associated with ECG measures indicative of subclinical myocardial dysfunction. These results may support future research investigating the significance of myocardial ischemia and volume overload in the pathogenesis of dysfunctional myocardial conduction in CKD.
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http://dx.doi.org/10.1093/ndt/gfaa296DOI Listing
December 2020

Change in Cardiac Biomarkers and Risk of Incident Heart Failure and Atrial Fibrillation in CKD: The Chronic Renal Insufficiency Cohort (CRIC) Study.

Am J Kidney Dis 2021 06 9;77(6):907-919. Epub 2020 Dec 9.

Kidney Research Institute, University of Washington, Seattle, WA.

Rationale & Objective: Circulating cardiac biomarkers may signal potential mechanistic pathways involved in heart failure (HF) and atrial fibrillation (AF). Single measures of circulating cardiac biomarkers are strongly associated with incident HF and AF in chronic kidney disease (CKD). We tested the associations of longitudinal changes in the N-terminal fragment of the prohormone brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hsTnT), galectin-3, growth differentiation factor 15 (GDF-15), and soluble ST-2 (sST-2) with incident HF and AF in patients with CKD.

Study Design: Observational, case-cohort study design.

Setting & Participants: Adults with CKD enrolled in the Chronic Renal Insufficiency Cohort study.

Exposures: Biomarkers were measured at baseline and 2 years later among those without kidney failure. We created 3 categories of absolute change in each biomarker: the lowest quartile, the middle 2 quartiles, and the top quartile.

Outcomes: The primary outcomes were incident HF and AF.

Analytical Approach: Cox proportional hazards regression models were used to test the associations of the change categories of each cardiac biomarker with each outcome (with the middle 2 quartiles of change as the referent group), adjusting for potential confounders and baseline concentrations of each biomarker.

Results: The incident HF analysis included 789 participants (which included 138 incident HF cases), and the incident AF analysis included 774 participants (123 incident AF cases). In multivariable models, the top quartile of NT-proBNP change (>232pg/mL over 2years) was associated with increased risk of incident HF (HR, 1.79 [95% CI, 1.06-3.04]) and AF (HR, 2.32 [95% CI, 1.37-3.93]) compared with the referent group. Participants in the top quartile of sST2 change (>3.37ng/mL over 2years) had significantly greater risk of incident HF (HR, 1.89 [95% CI, 1.13-3.16]), whereas those in the bottom quartile (≤-3.78ng/mL over 2years) had greater risk of incident AF (HR, 2.43 [95% CI, 1.39-4.22]) compared with the 2 middle quartiles. There was no association of changes in hsTnT, galectin-3, or GDF-15 with incident HF or AF.

Limitations: Observational study.

Conclusions: In CKD, increases in NT-proBNP were significantly associated with greater risk of incident HF and AF, and increases in sST2 were associated with HF. Further studies should investigate whether these markers of subclinical cardiovascular disease can be modified to reduce the risk of cardiovascular disease in CKD.
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http://dx.doi.org/10.1053/j.ajkd.2020.09.021DOI Listing
June 2021

Mobile Health (mHealth) Technology: Assessment of Availability, Acceptability, and Use in CKD.

Am J Kidney Dis 2021 06 9;77(6):941-950.e1. Epub 2020 Dec 9.

Department of Medicine, Duke University School of Medicine, Durham, NC.

Rationale & Objective: Digital and mobile health (mHealth) technologies improve patient-provider communication and increase information accessibility. We assessed the use of technology, attitudes toward using mHealth technologies, and proficiency in using mHealth technologies among individuals with chronic kidney disease (CKD).

Study Design: Cross-sectional survey with open text responses.

Setting & Participants: Chronic Renal Insufficiency Cohort (CRIC) Study participants who completed current use and interest in using mHealth technologies questionnaires and the eHealth literacy Survey (eHEALS).

Exposure: Participant characteristics.

Outcomes: Use of technology (ie, internet, email, smartphone, and mHealth applications [apps]), interest in future mHealth use, and proficiency in using digital and mHealth technologies, or eHealth literacy, determined by eHEALS score.

Analytical Approach: Poisson regression and a qualitative content analysis of open-ended responses.

Results: Study participants (n = 932) had a mean age of 68 years old and an estimated glomerular filtration rate (eGFR) of 54 mL/min/1.73 m, and 59% were male. Approximately 70% reported current use of internet, email, and smartphones, and 35% used mHealth apps; only 27% had adequate eHealth literacy (eHEALS score ≥ 32). Participants <65 years of age (vs. ≥65), with more education, higher income, better cognition, and adequate health literacy reported more use of technology, and greater interest in using technologies. Participants of White (vs. non-White) race reported more use of internet and email but less interest in future use of mHealth. Younger age, higher annual income, and greater disease self-efficacy were associated with adequate eHealth literacy. Three themes regarding interest in using digital and mHealth technologies emerged: willingness, concerns, and barriers.

Limitations: Residual confounding, ascertainment bias.

Conclusions: Many individuals with CKD currently use the internet and smartphones and are interested in using mHealth in the future, but few use mHealth apps or have adequate eHealth literacy. mHealth technologies present an opportunity to engage individuals with CKD, especially members of racial or ethnic minority groups because those groups reported greater interest in using mHealth technology than the nonminority population. Further research is needed to identify strategies to overcome inadequate eHealth literacy.
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http://dx.doi.org/10.1053/j.ajkd.2020.10.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8154635PMC
June 2021

Catheter ablation of atrial arrhythmias following lung transplant: Electrophysiological findings and outcomes.

J Cardiovasc Electrophysiol 2021 01 25;32(1):49-57. Epub 2020 Nov 25.

Electrophysiology Section, Cardiovascular Division, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Introduction: Data on the mechanisms of atrial arrhythmias (AAs) and outcomes of catheter ablation (CA) in lung transplantation (LT) patients are insufficient. We evaluated the electrophysiologic features and outcomes of CA of AAs in LT patients. METHODS AND RESULTS: We conducted a retrospective study of all the LT patients who underwent CA for AAs at our institution between 2004 and 2019. A total of 15 patients (43% males, age: 61 ± 10 years) with a history of LT (60% bilateral and 40% unilateral) were identified. All patients had documented organized AA on surface electrocardiogram and seven patients also had atrial fibrillation (AF; 47% with >1 clinical arrhythmia). At electrophysiological study, 19 organized AAs were documented (48% focal and 52% macro-re-entrant). Focal atrial tachycardias/flutters were targeted along the pulmonary vein (PV) anastomotic site at the left inferior PV (n = 2), ridge and carina of the left superior PV (n = 2), left atrium (LA) posterior wall (n = 3), LA roof (n = 1), and tricuspid annulus (n = 1). Macro-re-entrant AAs included cavotricuspid isthmus-dependent flutter (n = 2), incisional LA flutter (n = 4), LA roof-dependent flutter (n = 1), and mitral annular flutter (n = 3). In patients with LA mapping (n = 13), PV reconnection on the side of the LT was found in six patients (40%, all with clinically documented AF), with a mean of 2.1 ± 0.9 PVs reconnected per patient. Patients with AF underwent successful PV isolation. After a median follow-up of 19 months (range: 6-86 months), 75% of patients remained free from recurrent AAs. No procedural major complications occurred.

Conclusion: In patients with prior LT, recurrent AAs are typically associated with substrate surrounding the surgical anastomotic lines and/or chronically reconnected PVs. CA of AAs in this population is safe and effective to achieve long-term arrhythmia control.
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http://dx.doi.org/10.1111/jce.14816DOI Listing
January 2021

Cardiac Biomarkers and Risk of Mortality in CKD (the CRIC Study).

Kidney Int Rep 2020 Nov 10;5(11):2002-2012. Epub 2020 Sep 10.

Kidney Research Institute, Seattle, Washington, USA.

Introduction: Cardiovascular disease (CVD) is the leading cause of mortality among individuals with chronic kidney disease (CKD). Cardiac biomarkers of myocardial distention, injury, and inflammation may signal unique pathways underlying CVD in CKD. In this analysis, we studied the association of baseline levels and changes in 4 traditional and novel cardiac biomarkers with risk of all-cause, CV, and non-CV mortality in a large cohort of patients with CKD.

Methods: Among 3664 adults with CKD enrolled in the Chronic Renal Insufficiency Cohort Study, we conducted a cohort study to examine the associations of baseline levels of N-terminal pro-B-type natriuretic peptide (NT-proBNP), cardiac high-sensitivity troponin T (hsTnT), growth differentiation factor-15 (GDF-15), and soluble ST-2 (sST-2) with risks of all-cause and cardiovascular (CV) mortality. Among a subcohort of 842 participants, we further examined the associations between change in biomarker levels over 2 years with risk of all-cause mortality. We used Cox proportional hazards regression models and adjusted for demographics, kidney function measures, cardiovascular risk factors, and medication use.

Results: After adjustment, elevated baseline levels of each cardiac biomarker were associated with increased risk of all-cause mortality: NT-proBNP (hazard ratio [HR] = 1.92, 95% confidence interval [CI] = 1.73-2.12); hsTnT (HR = 1.62, 95% CI = 1.48, 1.78]); GDF-15 (HR = 1.61, 95% CI = 1.46-1.78]); and sST-2 (HR = 1.26, CI = 1.16-1.37). Higher baseline levels of all 4 cardiac biomarkers were also associated with increased risk of CV. Declines in NT-proBNP (adjusted HR = 0.55, 95% CI = 0.36-0.86) and sST2 (HR = 0.55, 95% CI = 0.36-0.86]) over 2 years were associated with lower risk of all-cause mortality.

Conclusion: In a large cohort of CKD participants, elevations of NT-proBNP, hsTnT, GDF-15, and sST-2 were independently associated with greater risks of all-cause and CV mortality.
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http://dx.doi.org/10.1016/j.ekir.2020.08.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609912PMC
November 2020

Slope of Kidney Function and Its Association with Longitudinal Mortality and Cardiovascular Disease among Individuals with CKD.

J Am Soc Nephrol 2020 12 6;31(12):2912-2923. Epub 2020 Oct 6.

Center for Clinical Epidemiology and Biostatistics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.

Background: Slopes of eGFR have been associated with increased risks of death and cardiovascular events in a U-shaped fashion. Poor outcomes in individuals with rising eGFR are potentially attributable to sarcopenia, hemodilution, and other indicators of clinical deterioration.

Methods: To investigate the association between eGFR slopes and risks of death or cardiovascular events, accounting for multiple confounders, we studied 2738 individuals with moderate to severe CKD participating in the multicenter Chronic Renal Insufficiency Cohort (CRIC) Study. We used linear, mixed-effects models to estimate slopes with up to four annual eGFR assessments, and Cox proportional hazards models to investigate the association between slopes and the risks of death and cardiovascular events.

Results: Slopes of eGFR had a bell-shaped distribution (mean [SD], -1.5 [-2] ml/min per 1.73 m per year). Declines of eGFR that were steeper than the average decline associated with progressively increasing risks of death (hazard ratio [HR], 1.23; 95% confidence interval [95% CI], 1.09 to 1.39; for a slope 1 SD below the average) and cardiovascular events (HR, 1.19; 95% CI, 1.03 to 1.38). Rises of eGFR or declines lower than the average decline were not associated with the risk of death or cardiovascular events.

Conclusions: In a cohort of individuals with moderate to severe CKD, we observed steep declines of eGFR were associated with progressively increasing risks of death and cardiovascular events; however, we found no increased risks associated with eGFR improvement. These findings support the potential value of eGFR slopes in clinical assessment of adults with CKD.
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http://dx.doi.org/10.1681/ASN.2020040476DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790212PMC
December 2020

Ablation of Ventricular Arrhythmias From the Left Ventricular Apex in Patients Without Ischemic Heart Disease.

JACC Clin Electrophysiol 2020 09 27;6(9):1089-1102. Epub 2020 May 27.

Division of Cardiovascular Medicine, Electrophysiology Section, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Objectives: This study aimed to characterize the incidence, clinical characteristics, and electrocardiographic and electrophysiologic features of LVA VA in the absence of CAD and to describe the experience with catheter ablation (CA) in this group.

Background: The left ventricular apex (LVA) is a well-described source of ventricular arrhythmias (VAs) in patients with coronary artery disease (CAD) and history of apical infarction but is a rare source of VA in the absence of CAD.

Methods: Patients referred for CA of VA at our institution were retrospectively reviewed, and those with LVA VA in the absence of CAD were identified.

Results: Of 3,710 consecutive patients undergoing VA ablation, CA of LVA VA was performed in 24 patients (20 with monomorphic ventricular tachycardia, 4 with premature ventricular contractions or nonsustained ventricular tachycardia; 18 men; mean age: 54 ± 15 years). These cases comprised 10 of 35 (29%) hypertrophic cardiomyopathy, 9 of 789 (1.2%) nonischemic cardiomyopathy, and 5 of 1,432 (0.4%) idiopathic VA ablation procedures. VA QRS morphology was predominantly right bundle with slurred upstroke and right superior frontal plane axis with precordial transition ≤V3. Epicardial ablation was performed in 14 of 24 (58%). After a median of 1 procedure (range 1 to 4) at this institution and median follow-up of 47 months (range 0-176), VA recurred in 1 patient (4%).

Conclusions: LVA VA in the absence of CAD is unusual and may occur in patients with hypertrophic cardiomyopathy or nonischemic cardiomyopathy or, rarely, in the absence of structural heart disease. It can be recognized by characteristic ECG features. CA of LVA VA is challenging; multiple procedures, including epicardial approaches, may be required to achieve VA control over long-term follow-up.
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http://dx.doi.org/10.1016/j.jacep.2020.04.021DOI Listing
September 2020

COVID-19 and electrophysiology procedures-review, reset, reboot!!!

J Interv Card Electrophysiol 2020 Nov 15;59(2):303-305. Epub 2020 Sep 15.

Section of Cardiac Electrophysiology, Division of Cardiovascular Medicine, Perelman School of Medicine, University of Pennsylvania, 9 Founders Pavilion, Philadelphia, PA, 19104, USA.

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http://dx.doi.org/10.1007/s10840-020-00871-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490112PMC
November 2020

Characterization of cardiac mechanics and incident atrial fibrillation in participants of the Cardiovascular Health Study.

JCI Insight 2020 10 2;5(19). Epub 2020 Oct 2.

Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA.

Background: Left atrial (LA) and left ventricular (LV) remodeling are associated with atrial fibrillation (AF). The prospective associations of impairment in cardiac mechanical function, as assessed by speckle-tracking echocardiography, with incident AF are less clear.

Methods: In the Cardiovascular Health Study, a community-based cohort of older adults, participants free of AF with echocardiograms of adequate quality for speckle tracking were included. We evaluated the associations of indices of cardiac mechanics (LA reservoir strain, LV longitudinal strain, and LV early diastolic strain rate) with incident AF.

Results: Of 4341 participants with strain imaging, participants with lower LA reservoir strain were older, had more cardiometabolic risk factors, and had lower renal function at baseline. Over a median follow-up of 10 years, 497 (11.4%) participants developed AF. Compared with the highest quartile of LA reservoir strain, the lowest quartile of LA reservoir strain was associated with higher risk of AF after covariate adjustment, including LA volume and LV longitudinal strain (heart rate [HR], 1.80; 95% CI, 1.31-2.45; P < 0.001). The association of LA reservoir strain and AF was stronger in subgroups with higher blood pressure, NT-proBNP, and LA volumes. There were no associations of LV longitudinal strain and LV early diastolic strain rate with incident AF after adjustment for LA reservoir strain.

Conclusion: Lower LA reservoir strain was associated with incident AF, independent of LV mechanics, and with stronger associations in high-risk subgroups. These findings suggest that LA mechanical dysfunction precedes the development of AF. Therapies targeting LA mechanical dysfunction may prevent progression to AF.

Funding: This research was supported by contracts HHSN268201200036C, HHSN268200800007C, HHSN268201800001C, N01HC55222, N01HC85079, N01HC85080, N01HC85081, N01HC85082, N01HC85083, and N01HC85086 and grants KL2TR001424, R01HL107577, U01HL080295, and U01HL130114 from the NIH's National Center for Advancing Translational Sciences, and National Heart, Lung, and Blood Institute (NHLBI), with additional contribution from the National Institute of Neurological Disorders and Stroke (NINDS). Additional support was provided by R01AG023629 from the National Institute on Aging (NIA). A full list of principal CHS investigators and institutions can be found at CHS-NHLBI.org.
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http://dx.doi.org/10.1172/jci.insight.141656DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566702PMC
October 2020

Proteomics for personalized cardiovascular risk assessment: in pursuit of the Holy Grail.

Eur Heart J 2020 11;41(41):4008-4010

Division of Nephrology, San Francisco VA Medical Center, University of California, San Francisco, 4150 Clement St, San Francisco, CA 94121, USA.

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http://dx.doi.org/10.1093/eurheartj/ehaa661DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7672528PMC
November 2020

Associations Between Cardiac Biomarkers and Cardiac Structure and Function in CKD.

Kidney Int Rep 2020 Jul 7;5(7):1052-1060. Epub 2020 May 7.

Department of Medicine, University of Washington School of Medicine, Seattle, Washington, USA.

Introduction: Subclinical changes to cardiac structure and function detected with echocardiography precede the development of clinical heart failure (HF) in persons with chronic kidney disease (CKD). Circulating cardiac biomarkers may reflect these pathophysiological changes. This study investigated associations between established biomarkers (N-terminal pro-B-type natriuretic peptide [NT-proBNP] and high-sensitivity troponin T [hsTnT]) and novel biomarkers (growth differentiation factor 15 [GDF-15], galectin-3 [Gal-3], and soluble ST-2 [sST-2]), using echocardiographic measurements in persons with CKD.

Methods: In cross-sectional analyses among 2101 participants with mild to moderate CKD in the Chronic Renal Insufficiency Cohort (CRIC), biomarker levels measured at baseline were evaluated with echocardiographic measurements 1 year later. These included left ventricular mass index (LVMI), left ventricular end-systolic volume (LVESV), left ventricular end-diastolic volume (LVEDV), left ventricular ejection fraction (LVEF), and left atrial diameter (LAD). Multivariable linear regression analyses tested associations of each biomarker with echocardiographic measurements, adjusting for covariates.

Results: GDF-15 was significantly associated with higher LVMI (1.0 g/m; 95% CI, 0.4-1.7), LVESV (0.4 ml/m; 95% CI, 0.0-0.7), and LVEDV (0.6 ml/m; 95% CI, 0.1-1.1), but not with LVEF or LAD. These findings were not significant when adjusting for NT-proBNP and hsTnT. Gal-3 and sST-2 had no significant associations. Higher levels of NT-proBNP and hsTnT were associated with all echocardiographic measurements.

Conclusion: In patients with CKD, the novel biomarker GDF-15, a marker of inflammation and tissue injury, and clinical biomarkers NT-proBNP and hsTnT, were associated with echocardiographic measurements of subclinical cardiovascular disease. Collectively, these biomarkers may highlight biological pathways that contribute to the development of clinical HF.
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http://dx.doi.org/10.1016/j.ekir.2020.04.031DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7335964PMC
July 2020

COVID-19 and cardiac arrhythmias.

Heart Rhythm 2020 Sep 22;17(9):1439-1444. Epub 2020 Jun 22.

Division of Cardiovascular Medicine, Department of Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address:

Background: Early studies suggest that coronavirus disease 2019 (COVID-19) is associated with a high incidence of cardiac arrhythmias. Severe acute respiratory syndrome coronavirus 2 infection may cause injury to cardiac myocytes and increase arrhythmia risk.

Objectives: The purpose of this study was to evaluate the risk of cardiac arrest and arrhythmias including incident atrial fibrillation (AF), bradyarrhythmias, and nonsustained ventricular tachycardia (NSVT) in a large urban population hospitalized for COVID-19. We also evaluated correlations between the presence of these arrhythmias and mortality.

Methods: We reviewed the characteristics of all patients with COVID-19 admitted to our center over a 9-week period. Throughout hospitalization, we evaluated the incidence of cardiac arrests, arrhythmias, and inpatient mortality. We also used logistic regression to evaluate age, sex, race, body mass index, prevalent cardiovascular disease, diabetes, hypertension, chronic kidney disease, and intensive care unit (ICU) status as potential risk factors for each arrhythmia.

Results: Among 700 patients (mean age 50 ± 18 years; 45% men; 71% African American; 11% received ICU care), there were 9 cardiac arrests, 25 incident AF events, 9 clinically significant bradyarrhythmias, and 10 NSVTs. All cardiac arrests occurred in patients admitted to the ICU. In addition, admission to the ICU was associated with incident AF (odds ratio [OR] 4.68; 95% confidence interval [CI] 1.66-13.18) and NSVT (OR 8.92; 95% CI 1.73-46.06) after multivariable adjustment. Also, age and incident AF (OR 1.05; 95% CI 1.02-1.09) and prevalent heart failure and bradyarrhythmias (OR 9.75; 95% CI 1.95-48.65) were independently associated. Only cardiac arrests were associated with acute in-hospital mortality.

Conclusion: Cardiac arrests and arrhythmias are likely the consequence of systemic illness and not solely the direct effects of COVID-19 infection.
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http://dx.doi.org/10.1016/j.hrthm.2020.06.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7307518PMC
September 2020

Association of Cardiac Biomarkers With the Kansas City Cardiomyopathy Questionnaire in Patients With Chronic Kidney Disease Without Heart Failure.

J Am Heart Assoc 2020 07 24;9(13):e014385. Epub 2020 Jun 24.

Kidney Research Institute University of Washington Seattle WA.

Background The Kansas City Cardiomyopathy Questionnaire (KCCQ) is a measure of heart failure (HF) health status. Worse KCCQ scores are common in patients with chronic kidney disease (CKD), even without diagnosed heart failure (HF). Elevations in the cardiac biomarkers GDF-15 (growth differentiation factor-15), galectin-3, sST2 (soluble suppression of tumorigenesis-2), hsTnT (high-sensitivity troponin T), and NT-proBNP (N-terminal pro-B-type natriuretic peptide) likely reflect subclinical HF in CKD. Whether cardiac biomarkers are associated with low KCCQ scores is not known. Methods and Results We studied participants with CKD without HF in the multicenter prospective CRIC (Chronic Renal Insufficiency Cohort) Study. Outcomes included (1) low KCCQ score <75 at year 1 and (2) incident decline in KCCQ score to <75. We used multivariable logistic regression and Cox regression models to evaluate the associations between baseline cardiac biomarkers and cross-sectional and longitudinal KCCQ scores. Among 2873 participants, GDF-15 (adjusted odds ratio 1.42 per SD; 99% CI, 1.19-1.68) and galectin-3 (1.28; 1.12-1.48) were significantly associated with KCCQ scores <75, whereas sST2, hsTnT, and NT-proBNP were not significantly associated with KCCQ scores <75 after multivariable adjustment. Of the 2132 participants with KCCQ ≥75 at year 1, GDF-15 (adjusted hazard ratio, 1.36 per SD; 99% CI, 1.12-1.65), hsTnT (1.20; 1.01-1.44), and NT-proBNP (1.30; 1.08-1.56) were associated with incident decline in KCCQ to <75 after multivariable adjustment, whereas galectin-3 and sST2 did not have significant associations with KCCQ decline. Conclusions Among participants with CKD without clinical HF GDF-15, galectin-3, NT-proBNP, and hsTnT were associated with low KCCQ either at baseline or during follow-up. Our findings show that elevations in cardiac biomarkers reflect early symptomatic changes in HF health status in CKD patients.
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http://dx.doi.org/10.1161/JAHA.119.014385DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7670503PMC
July 2020
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