Empagliflozin in Heart Failure: Regional Nephron Sodium Handling Effects.

SIGNIFICANCE STATEMENT: The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on regional tubular sodium handling is poorly understood in humans. In this study, empagliflozin substantially decreased lithium reabsorption in the proximal tubule (PT) (a marker of proximal tubular sodium reabsorption), a magnitude out of proportion to that expected with only inhibition of sodium-glucose cotransporter-2. This finding was not driven by an "osmotic diuretic" effect; however, several parameters changed in a manner consistent with inhibition of the sodium-hydrogen exchanger 3. The large changes in proximal tubular handling were acutely buffered by increased reabsorption in both the loop of Henle and the distal nephron, resulting in the observed modest acute natriuresis with these agents. After 14 days of empagliflozin, natriuresis waned due to increased reabsorption in the PT and/or loop of Henle. These findings confirm in humans that SGLT2i have complex and important effects on renal tubular solute handling. BACKGROUND: The effect of SGLT2i on regional tubular sodium handling is poorly understood in humans but may be important for the cardiorenal benefits. METHODS: This study used a previously reported randomized, placebo-controlled crossover study of empagliflozin 10 mg daily in patients with diabetes and heart failure. Sodium handling in the PT, loop of Henle (loop), and distal nephron was assessed at baseline and day 14 using fractional excretion of lithium (FELi), capturing PT/loop sodium reabsorption. Assessments were made with and without antagonism of sodium reabsorption through the loop using bumetanide. RESULTS: Empagliflozin resulted in a large decrease in sodium reabsorption in the PT (increase in FELi=7.5%±10.6%, P = 0.001), with several observations suggesting inhibition of PT sodium hydrogen exchanger 3. In the absence of renal compensation, this would be expected to result in approximately 40 g of sodium excretion/24 hours with normal kidney function. However, rapid tubular compensation occurred with increased sodium reabsorption both in the loop ( P < 0.001) and distal nephron ( P < 0.001). Inhibition of sodium-glucose cotransporter-2 did not attenuate over 14 days of empagliflozin ( P = 0.14). However, there were significant reductions in FELi ( P = 0.009), fractional excretion of sodium ( P = 0.004), and absolute fractional distal sodium reabsorption ( P = 0.036), indicating that chronic adaptation to SGLT2i results primarily from increased reabsorption in the loop and/or PT. CONCLUSIONS: Empagliflozin caused substantial redistribution of intrarenal sodium delivery and reabsorption, providing mechanistic substrate to explain some of the benefits of this class. Importantly, the large increase in sodium exit from the PT was balanced by distal compensation, consistent with SGLT2i excellent safety profile. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: ClinicalTrials.gov ( NCT03027960 ).

Insulin Requirement and Infrainguinal Bypass Outcomes in Patients with Peripheral Arterial Disease.

BACKGROUND: Diabetes mellitus (DM) is a major risk factor for peripheral artery disease. The association of DM with major adverse limb events (MALE) after lower extremity revascularization remains controversial, as patients with diabetes are typically analyzed as a single, homogenous group. Using a large national database, this study examines the impact of insulin use and glycemic control on the outcomes following infrainguinal bypass. The hypothesis is that prevalent insulin therapy and elevated hemoglobin A1c (HbA1c) are associated with an increased risk of MALEs after infrainguinal bypass in patients with DM and could therefore be used for risk stratification. METHODS: The Vascular Quality Initiative database files for infrainguinal bypass (2007-2021) were retrospectively reviewed. Patients with DM undergoing bypass for peripheral artery disease were included. Patients on dialysis or with prior kidney transplantation were excluded. The characteristics and outcomes of patients with insulin-requiring diabetes mellitus (IRDM) were compared to those of patients not requiring insulin (noninsulin-requiring diabetes mellitus [NIRDM]) prior to the bypass procedure. RESULTS: A total of 9,686 patients with DM (56% IRDM) underwent bypass. Patients with IRDM were significantly younger than patients with NIRDM, more likely to be female (P < 0.01), African American (P < 0.01), and Hispanic (P = 0.031), and more likely to have comorbidities and be categorized into American Society of Anesthesiologist classes IV-V. They were more likely to be treated for chronic limb-threatening ischemia (P < 0.001). Patients with IRDM had significantly higher perioperative complications with no difference in perioperative mortality between the 2 groups. Beyond the perioperative period, with a mean follow-up of 427 days, patients with IRDM had significantly lower crude rates of primary patency and higher crude rates of major amputation, MALE, and mortality compared to patients with NIRDM. Regression analyses demonstrated that insulin requirement, but not HbA1c, was independently associated with a higher risk of MALE (hazard ratio = 1.17 [1.06-1.29]) and mortality (hazard ratio = 1.28 [1.16-1.43]). CONCLUSIONS: Insulin requirement, but not HbA1c, is significantly associated with MALEs and survival after infrainguinal bypass in the Vascular Quality Initiative. Stratification of patients with DM based on their prevalent insulin use prior to infrainguinal bypass surgery could improve the prediction of outcomes of peripheral arterial bypass surgery in patients with diabetes.

In the "Plant-Based" Era, Patients With Chronic Kidney Disease Should Focus on Eating Healthy.

In the era of plant-based diets, it is important for Nephrology providers to know the evidence regarding their healthfulness in patients with chronic kidney disease (CKD). A whole food, plant-based diet, which emphasizes fresh, minimally processed or refined plant-based foods and limits animal products, has shown benefits for patients with CKD. These include reduced dietary acid load, lower bioavailability of potassium and phosphorus, increased dietary fiber intake, nutritional adequacy, and cardiovascular and mortality benefits. Potential drawbacks include the need for specific knowledge, skills, and cost involved in preparing varied, healthy, and appetizing plant-based meals, leading to lower acceptability and accessibility to certain populations. Liberalization of the standard CKD diet to include healthy, minimally processed foods such as fruits, vegetables, nuts, legumes, and whole grains is likely beneficial, though more research is needed to determine whether a plant-based-only diet is the optimal way to achieve healthier eating in patients with CKD.

Circular external fixation for revision of failed tibia internal fixation.

BACKGROUND: The management of failed tibial fracture fixation remains a challenge for orthopaedic surgeons. This study investigate the utility and outcomes of circular external fixation in the management of failed internal fixation of tibial fractures. METHODS: Retrospective review of a prospectively collected database of a complex limb reconstruction unit at a major trauma centre was done during December 2022. Patients with failed internal fixation of tibial fracture who underwent revision surgery with circular external fixation frame were included. RESULTS: 20 patients with a mean age of 47.8 ± 16.5 years (range: 15-69) were included. Fourteen (70.0%) patients had failed plate and screws fixations, and the remaining six (30.0%) failed intramedullary nail fixation. The most common indication for revision surgery was development of early postoperative surgical site infection (5 patients; 25.0%). The mean duration of frame treatment was 199.5 ± 80.1 days (range = 49-364), while the mean follow-up duration following frame removal was 3.2 ± 1.8 years (range = 2-8). The overall union rate in this series was 100%; and all infected cases had complete resolution from infection. The total number of complications was 11, however, only two complications required surgical intervention. The most common complications reported were pin site infection (6; 30.0%) and limb length discrepancy of 2 cm (2; 10.0%). CONCLUSIONS: Circular external fixation is a reliable surgical option in the treatment of failed internal fixation of tibia fractures. This technique can provide limb salvage in complex infected and noninfected cases with a high union rate and minimal major complications.

Carbon dioxide angiography during peripheral vascular interventions is associated with decreased cardiac and renal complications in patients with chronic kidney disease.

OBJECTIVE: Patients with chronic kidney disease (CKD) who undergo peripheral vascular interventions (PVI) with iodinated contrast are at higher risk of post-contrast acute kidney injury (PC-AKI). Carbon dioxide (CO2) angiography can reduce iodinated contrast volume usage in this patient population, but its impact on PC-AKI has not been studied. We hypothesize that CO2 angiography is associated with a decrease in PC-AKI in patients with advanced CKD. METHODS: The Vascular Quality Initiative PVI dataset from 2010 to 2021 was reviewed. Only patients with advanced CKD (estimated glomular filtration rate <45 ml/min/1.73 m2) treated for peripheral arterial disease were included. Propensity matching and multivariate logistic regression based on demographics, comorbidities, CKD stage, and indications were used to compare the outcomes of patients treated with and without CO2. RESULTS: There were 20,706 PVIs performed in patients with advanced CKD, and only 22% utilized CO2 angiography. Compared with patients treated without CO2, patients who underwent CO2 angiography were younger and less likely to be women or White, and more likely to have poor renal function, diabetes, cardiac comorbidities, and present with tissue loss. Propensity matching yielded well-matched groups with 4472 patients in each group. The procedural details after matching demonstrated 50% reduction in the volume of contrast used (32±33 vs 65±48 mL; P < .01). PVI with CO2 angiography was associated with lower rates of PC-AKI (3.9% vs 4.8%; P = .03) and cardiac complications (2.1% vs 2.9%; P = .03) without a significant difference in technical failure or major/minor amputations. Low contrast volumes (≤50 mL for CKD3, ≤20 mL for CKD4, and ≤9 mL for CKD5) are associated with reduced risk of PC-AKI (hazard ratio, 0.59; P < .01). CONCLUSIONS: CO2 angiography reduces iodinated contrast volume usage during PVI and is associated with decreased cardiac complications and PC-AKI. CO2 angiography is underutilized and should be considered for patients with advanced CKD who require endovascular therapy.

Current and Developing Technologies for BP Monitoring.

PURPOSE OF REVIEW: To discuss new and emerging technologies for blood pressure measurement and monitoring, including the limitations of current blood pressure measurement techniques, hopes for new device technologies, and the current barriers impeding change in this space. RECENT FINDINGS: A number of new cuffless devices are being developed and poised to emerge on the marketplace in coming years. There are several different types of technologies and sensors currently under study. New guidelines for validation of cuffless blood pressure devices have recently been developed in anticipation of this change. The current standards for blood pressure device validation are specific to cuff-based technology and are insufficient for validating devices with cuffless-based technologies. In anticipation of a number of new cuffless technologies coming to market in the coming years, three sets of standards have been developed and published in recent years to address this gap.

Compensatory post-diuretic renal sodium reabsorption is not a dominant mechanism of diuretic resistance in acute heart failure.

AIMS: In healthy volunteers, the kidney deploys compensatory post-diuretic sodium reabsorption (CPDSR) following loop diuretic-induced natriuresis, minimizing sodium excretion and producing a neutral sodium balance. CPDSR is extrapolated to non-euvolemic populations as a diuretic resistance mechanism; however, its importance in acute decompensated heart failure (ADHF) is unknown. METHODS AND RESULTS: Patients with ADHF in the Mechanisms of Diuretic Resistance cohort receiving intravenous loop diuretics (462 administrations in 285 patients) underwent supervised urine collections entailing an immediate pre-diuretic spot urine sample, then 6-h (diuretic-induced natriuresis period) and 18-h (post-diuretic period) urine collections. The average spot urine sodium concentration immediately prior to diuretic administration [median 15 h (13-17) after last diuretic] was 64 ± 33 mmol/L with only 4% of patients having low (<20 mmol/L) urine sodium consistent with CPDSR. Paradoxically, greater 6-h diuretic-induced natriuresis was associated with larger 18-h post-diuretic spontaneous natriuresis (r = 0.7, P < 0.001). Higher pre-diuretic urine sodium to creatinine ratio (r = 0.37, P < 0.001) was the strongest predictor of post-diuretic spontaneous natriuresis. In a subgroup of patients (n = 43) randomized to protocol-driven intensified diuretic therapies, the mean diuretic-induced natriuresis increased three-fold. In contrast to the substantial decrease in spontaneous natriuresis predicted by CPDSR, no change in post-diuretic spontaneous natriuresis was observed (P = 0.47). CONCLUSION: On a population level, CPDSR was not an important driver of diuretic resistance in hypervolemic ADHF. Contrary to CPDSR, a greater diuretic-induced natriuresis predicted a larger post-diuretic spontaneous natriuresis. Basal sodium avidity, rather than diuretic-induced CPDSR, appears to be the predominant determinate of both diuretic-induced and post-diuretic natriuresis in hypervolemic ADHF.

First-in-Human Experience With Peritoneal Direct Sodium Removal Using a Zero-Sodium Solution: A New Candidate Therapy for Volume Overload.

BACKGROUND: Loop diuretics have well-described toxicities, and loss of response to these agents is common. Alternative strategies are needed for the maintenance of euvolemia in heart failure (HF). Nonrenal removal of sodium directly across the peritoneal membrane (direct sodium removal [DSR]) with a sodium-free osmotic solution should result in extraction of large quantities of sodium with limited off-target solute removal. METHODS: This article describes the preclinical development and first-in-human proof of concept for DSR. Sodium-free 10% dextrose was used as the DSR solution. Porcine experiments were conducted to investigate the optimal dwell time, safety, and scalability and to determine the effect of experimental heart failure. In the human study, participants with end-stage renal disease on peritoneal dialysis (PD) underwent randomization and crossover to either a 2-hour dwell with 1 L DSR solution or standard PD solution (Dianeal 4.25% dextrose, Baxter). The primary end point was completion of the 2-hour dwell without significant discomfort or adverse events, and the secondary end point was difference in sodium removal between DSR and standard PD solution. RESULTS: Porcine experiments revealed that 1 L DSR solution removed 4.1±0.4 g sodium in 2 hours with negligible off-target solute removal and overall stable serum electrolytes. Increasing the volume of DSR solution cycled across the peritoneum increased sodium removal and substantially decreased plasma volume (P=0.005). In the setting of experimental heart failure with elevated right atrial pressure, sodium removal was ≈4 times greater than in healthy animals (P<0.001). In the human proof-of-concept study, DSR solution was well tolerated and not associated with significant discomfort or adverse events. Plasma electrolyte concentrations were stable, and off-target solute removal was negligible. Sodium removal was substantially higher with DSR (4.5±0.4 g) compared with standard PD solution (1.0±0.3 g; P<0.0001). CONCLUSIONS: DSR was well tolerated in both animals and human subjects and produced substantially greater sodium removal than standard PD solution. Additional research evaluating the use of DSR as a method to prevent and treat hypervolemia in heart failure is warranted. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03801226.

Empagliflozin in Heart Failure: Diuretic and Cardiorenal Effects.

BACKGROUND: Sodium-glucose cotransporter-2 inhibitors improve heart failure-related outcomes. The mechanisms underlying these benefits are not well understood, but diuretic properties may contribute. Traditional diuretics such as furosemide induce substantial neurohormonal activation, contributing to the limited improvement in intravascular volume often seen with these agents. However, the proximal tubular site of action of the sodium-glucose cotransporter-2 inhibitors may help circumvent these limitations. METHODS: Twenty patients with type 2 diabetes mellitus and chronic, stable heart failure completed a randomized, placebo-controlled crossover study of empagliflozin 10 mg daily versus placebo. Patients underwent an intensive 6-hour biospecimen collection and cardiorenal phenotyping at baseline and again after 14 days of study drug. After a 2-week washout, patients crossed over to the alternate therapy with the above protocol repeated. RESULTS: Oral empagliflozin was rapidly absorbed as evidenced by a 27-fold increase in urinary glucose excretion by 3 hours (P<0.0001). Fractional excretion of sodium increased significantly with empagliflozin monotherapy versus placebo (fractional excretion of sodium, 1.2±0.7% versus 0.7±0.4%; P=0.001), and there was a synergistic effect in combination with bumetanide (fractional excretion of sodium, 5.8±2.5% versus 3.9±1.9%; P=0.001). At 14 days, the natriuretic effect of empagliflozin persisted, resulting in a reduction in blood volume (-208 mL [interquartile range, -536 to 153 mL] versus -14 mL [interquartile range, -282 to 335 mL]; P=0.035) and plasma volume (-138 mL, interquartile range, -379 to 154±453 mL; P=0.04). This natriuresis was not, however, associated with evidence of neurohormonal activation because the change in norepinephrine was superior (P=0.02) and all other neurohormones were similar (P<0.34) during the empagliflozin versus placebo period. Furthermore, there was no evidence of potassium wasting (P=0.20) or renal dysfunction (P>0.11 for all biomarkers), whereas both serum magnesium (P<0.001) and uric acid levels (P=0.008) improved. CONCLUSIONS: Empagliflozin causes significant natriuresis, particularly when combined with loop diuretics, resulting in an improvement in blood volume. However, off-target electrolyte wasting, renal dysfunction, and neurohormonal activation were not observed. This favorable diuretic profile may offer significant advantage in the management of volume status in patients with heart failure and may represent a mechanism contributing to the superior long-term heart failure outcomes observed with these agents. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03027960.

Renal negative pressure treatment as a novel therapy for heart failure-induced renal dysfunction.

Congestion is the primary pathophysiological lesion in most heart failure (HF) hospitalizations. Renal congestion increases renal tubular pressure, reducing glomerular filtration rate (GFR) and diuresis. Because each nephron is a fluid-filled column, renal negative pressure therapy (rNPT) applied to the urinary collecting system should reduce tubular pressure, potentially improving kidney function. We evaluated the renal response to rNPT in congestive HF. Ten anesthetized ∼80-kg pigs underwent instrumentation with bilateral renal pelvic JuxtaFlow catheters. GFR was determined by iothalamate clearance (mGFR) and renal plasma flow (RPF) by para-aminohippurate clearance. Each animal served as its own control with randomization of left versus right kidney to -30 mmHg rNPT or no rNPT. mGFR and RPF were measured simultaneously from the rNPT and no rNPT kidney. Congestive HF was induced via cardiac tamponade maintaining central venous pressure at 20-22.5 mmHg throughout the experiment. Before HF induction, rNPT increased natriuresis, diuresis, and mGFR compared with the control kidney (P < 0.001 for all). Natriuresis, diuresis, and mGFR decreased following HF (P < 0.001 for all) but were higher in rNPT kidney versus control (P < 0.001 for all). RPF decreased during HF (P < 0.001) without significant differences between rNPT treatments. During HF, the rNPT kidney had similar diuresis and natriuresis (P > 0.5 for both) and higher fractional excretion of sodium (P = 0.001) compared with the non-rNPT kidney in the no HF period. In conclusion, rNPT resulted in significantly increased diuresis, natriuresis, and mGFR, with or without experimental HF. rNPT improved key renal parameters of the congested cardiorenal phenotype.

Cystatin C and Muscle Mass in Patients With Heart Failure.

BACKGROUND: The estimated glomerular filtration rate (eGFR) from cystatin C (eGFRcys) is often considered a more accurate method to assess GFR compared with an eGFR from creatinine (eGFRcr) in the setting of heart failure (HF) and sarcopenia, because cystatin C is hypothesized to be less affected by muscle mass than creatinine. We evaluated (1) the association of muscle mass with cystatin C, (2) the accuracy of eGFRcys, and (3) the association of eGFRcys with mortality given muscle mass. METHODS AND RESULTS: We included 293 patients admitted with HF. Muscle mass was estimated with a validated creatinine excretion-based equation. Accuracy of eGFRcys and eGFRcr was compared with measured creatinine clearance. Cystatin C and creatinine were 31.7% and 59.9% higher per 14 kg higher muscle mass at multivariable analysis (both P < .001). At lower muscle mass, eGFRcys and eGFRcr overestimated the measured creatinine clearance. At higher muscle mass, eGFRcys underestimated the measured creatinine clearance, but eGFRcr did not. After adjusting for muscle mass, neither eGFRcys nor eGFRcr were associated with mortality (both P > .19). CONCLUSIONS: Cystatin C levels were associated with muscle mass in patients with HF, which could potentially decrease the accuracy of eGFRcys. In HF where aberrations in body composition are common, eGFRcys, like eGFRcr, may not provide accurate GFR estimations and results should be interpreted cautiously.

Guideline-Directed Medical Therapy in Patients with Chronic Kidney Disease Undergoing Peripheral Vascular Intervention.

INTRODUCTION: Guideline-directed medical therapy (GDMT) is imperative to improve cardiovascular and limb outcomes for patients with critical limb ischemia (CLI), especially amongst those at highest risk for poor outcomes, including those with comorbid chronic kidney disease (CKD). Our objective was to examine GDMT prescription rates and their variation across individual sites for patients with CLI undergoing peripheral vascular interventions (PVIs), by their comorbid CKD status. METHODS: Patients with CLI who underwent PVI (October 2016-April 2019) were included from the Vascular Quality Initiative (VQI) database. CKD was defined as GFR <60 mL/min/1.73 m2. GDMT included the composite use of antiplatelet therapy and a statin, as well as an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if hypertension was present. The use of GDMT before and after the index procedure was summarized in those with and without CKD. Adjusted median odds ratios (MORs) for site variability were calculated. RESULTS: The study included 28,652 patients, with a mean age of 69.4 ± 11.7 years, and 40.8% were females. A total of 47.5% had CKD. Patients with CKD versus those without CKD had lower prescription rates both before (31.7% vs. 38.9%) and after (36.5% vs. 48.8%) PVI (p < 0.0001). Significant site variability was observed in the delivery of GDMT in both the non-CKD and CKD groups before and after PVI (adjusted MORs: 1.31-1.41). DISCUSSION/CONCLUSION: In patients with CLI undergoing PVI, patients with comorbid CKD were less likely to receive GDMT. Significant variability of GDMT was observed across sites. These findings indicate that significant improvements must be made in the medical management of patients with CLI, particularly in patients at high risk for poor clinical outcomes.

Relationship between Rainfall, Fecal Pollution, Antimicrobial Resistance, and Microbial Diversity in an Urbanized Subtropical Bay.

Urbanized bays are vulnerable to fecal bacterial pollution, and the extent of this pollution, in marine recreational waters, is commonly assessed by quantifying enterococcus concentrations. Recent reports have questioned the utility of enterococci as an indicator of fecal bacterial pollution in subtropical bays impaired by non-point source pollution, and enterococcus data alone cannot identify fecal bacterial sources (i.e., hosts). The purpose of this study was to assess relationships between rainfall, fecal bacterial pollution, antimicrobial resistance, and microbial diversity in an urbanized subtropical bay. Thus, a comprehensive bacterial source tracking (BST) study was conducted using a combination of traditional and modern BST methods. Findings show that rainfall was directly correlated with elevated enterococcus concentrations, including the increased prevalence of Enterococcus faecium, although it was not correlated with an increase in the prevalence of antimicrobial-resistant strains. Rainfall was also correlated with decreased microbial diversity. In contrast, neither rainfall nor enterococcus concentrations were directly correlated with the concentrations of three omnipresent host-associated fecal markers (i.e., human, canine, and gull). Notably, the human fecal marker (HF183) was inversely correlated with enterococcus concentrations, signifying that traditional enterococcus data alone are not an accurate proxy for human fecal waste in urbanized subtropical bays.IMPORTANCE The presence of human enteric pathogens, stemming from fecal pollution, is a serious environmental and public health concern in recreational waters. Accurate assessments of fecal pollution are therefore needed to properly assess exposure risks and guide water quality policies and practices. In this study, the absence of a direct correlation between enterococci and source-specific human and animal markers disputes the utility of enterococci as an indicator of fecal pollution in urbanized subtropical bays. Moreover, the inverse correlation between enterococci and the human-specific marker HF183 indicates that recreational beach advisories, triggered by elevated enterococcus concentrations, are a misleading practice. This study clearly demonstrates that a multiparameter approach that includes the quantitation of host-specific markers, as well as analyses of microbial diversity, is a more effective means of assessing water quality in urbanized subtropical bays.

Patient-reported outcomes and subsequent management in atrial fibrillation clinical practice: Results from the Utah mEVAL AF program.

BACKGROUND: Atrial fibrillation (AF) significantly reduces health-related quality of life (HRQoL), previously measured in clinical trials using patient-reported outcomes (PROs). We examined AF PROs in clinical practice and their association with subsequent clinical management. METHODS: The Utah My Evaluation (mEVAL) program collects the Toronto AF Symptom Severity Scale (AFSS) in AF outpatients at the University of Utah. Baseline factors associated with worse AF symptom score (range 0-35, higher is worse) were identified in univariate and multivariable analyses. Secondary outcomes included AF burden and AF healthcare utilization. We also compared subsequent clinical management at 6 months between patients with better versus worse AF HRQoL. RESULTS: Overall, 1338 patients completed the AFSS symptom score, which varied by sex (mean 7.26 for males vs. 10.27 for females; p < .001), age (<65, 9.73; 65-74, 7.66; ≥75, 7.58; p < .001), heart failure (9.39 with HF vs. 7.67 without; p < .001), and prior ablation (7.28 with prior ablation vs. 8.84; p < .001). In multivariable analysis, younger age (mean difference 2.92 for <65 vs. ≥75; p < .001), female sex (mean difference 2.57; p < .001), pulmonary disease (mean difference 1.88; p < .001), and depression (mean difference 2.46; p < .001) were associated with higher scores. At 6-months, worse baseline symptom score was associated with the use of rhythm control (37.1% vs. 24.5%; p < .001). Similar cofactors and results were associated with increased AF burden and health care utilization scores. CONCLUSIONS: AF PROs in clinical practice identify highly-symptomatic patients, corroborating findings in more controlled, clinical trials. Increased AFSS score correlates with more aggressive clinical management, supporting the utility of disease-specific PROs guiding clinical practice.

Impact of Kidney Disease on Peripheral Arterial Interventions: A Systematic Review and Meta-Analysis.

BACKGROUND: There are limited data on outcomes of patients undergoing peripheral arterial disease (PAD) interventions who have comorbid CKD/ESRD versus those who do not have such comorbid condition. We performed a systematic review and meta-analysis to analyze outcomes in this patient population. METHODS: Five databases were searched for studies comparing outcomes of lower extremity PAD interventions for claudication and critical limb ischemia (CLI) in patients with CKD/ESRD versus non-CKD/non-ESRD from January 2000 to June 2019. RESULTS: Our study included 16 observational studies with 44,138 patients. Mean follow-up was 48.9 ± 27.4 months. Major amputation was higher with CKD/ESRD compared with non-CKD/non-ESRD (odds ratio [OR 1.97] [95% confidence interval [CI] 1.39-2.80], p = 0.001). Higher major amputations with CKD/ESRD versus non-CKD/non-ESRD were only observed when indication for procedure was CLI (OR 2.27 [95% CI 1.53-3.36], p < 0.0001) but were similar for claudication (OR 1.15 [95% CI 0.53-2.49], p = 0.72). The risk of early mortality was high with CKD/ESRD patients undergoing PAD interventions compared with non-CKD/non-ESRD (OR 2.55 [95% CI 1.65-3.96], p < 0.0001), which when stratified based on indication, remained higher with CLI (OR 3.14 [95% CI 1.80-5.48], p < 0.0001) but was similar with claudication (OR 1.83 [95% CI 0.90-3.72], p = 0.1). Funnel plot of included studies showed moderate bias. CONCLUSIONS: Patients undergoing lower extremity PAD interventions for CLI who also have comorbid CKD/ESRD have an increased risk of experiencing major amputations and early mortality. Randomized trials to understand outcomes of PAD interventions in this at-risk population are essential.

Systematic collection of patient-reported outcomes in atrial fibrillation: feasibility and initial results of the Utah mEVAL AF programme.

AIMS: Incorporating patient-reported outcomes (PROs) into routine care of atrial fibrillation (AF) enables direct integration of symptoms, function, and health-related quality of life (HRQoL) into practice. We report our initial experience with a system-wide PRO initiative among AF patients. METHODS AND RESULTS: All patients with AF in our practice undergo PRO assessment with the Toronto AF Severity Scale (AFSS), and generic PROs, prior to electrophysiology clinic visits. We describe the implementation, feasibility, and results of clinic-based, electronic AF PRO collection, and compare AF-specific and generic HRQoL assessments. From October 2016 to February 2019, 1586 unique AF patients initiated 2379 PRO assessments, 2145 of which had all PRO measures completed (90%). The median completion time for all PRO measures per visit was 7.3 min (1st, 3rd quartiles: 6, 10). Overall, 38% of patients were female (n = 589), mean age was 68 (SD 12) years, and mean CHA2DS2-VASc score was 3.8 (SD 2.0). The mean AFSS symptom score was 8.6 (SD 6.6, 1st, 3rd quartiles: 3, 13), and the full range of values was observed (0, 35). Generic PROs of physical function, general health, and depression were impacted at the most severe quartiles of AF symptom score (P < 0.0001 for each vs. AFSS quartile). CONCLUSION: Routine clinic-based, PRO collection for AF is feasible in clinical practice and patient time investment was acceptable. Disease-specific AF PROs add value to generic HRQoL instruments. Further research into the relationship between PROs, heart rhythm, and AF burden, as well as PRO-guided management, is necessary to optimize PRO utilization.

Should Angiotensin-Converting Enzyme Inhibitors ever Be Used for the Management of Hypertension?

PURPOSE OF REVIEW: Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly used anti-hypertensive medications in a number of clinical settings. They are often used interchangeably, but we pose the provocative question as to whether they should be. We review the literature to evaluate for any differences in efficacy between the two classes in order to determine if the greater side effects associated with angiotensin-converting enzyme inhibitors are offset by any advantageous effects on outcomes to warrant their use over angiotensin receptor blockers. RECENT FINDINGS: In many clinical scenarios, the data supports similar efficacy between ACE inhibitors and ARBs, while in a minority of others, there are murky signals from previous trials that suggest ACE inhibitors may be better. However, when reviewing the literature in its entirety, and taking into account recently published pooled analysis and head to head trials, it is reasonable to conclude that ACE inhibitors and ARBs have similar efficacy. This is in contrast to data on adverse effects, which consistently favors the use of ARBs. From the available data, it is reasonable to conclude that ACE inhibitors and ARBs have equal efficacy yet unequal adverse effects. It is in this context that we take the provocative stance that ACE inhibitors should not be used to treat hypertension.

Are We Underestimating Microplastic Contamination in Aquatic Environments?

Plastic debris, specifically microplastic in the aquatic environment, is an escalating environmental crisis. Efforts at national scales to reduce or ban microplastics in personal care products are starting to pay off, but this will not affect those materials already in the environment or those that result from unregulated products and materials. To better inform future microplastic research and mitigation efforts this study (1) evaluates methods currently used to quantify microplastics in the environment and (2) characterizes the concentration and size distribution of microplastics in a variety of products. In this study, 50 published aquatic surveys were reviewed and they demonstrated that most (~80%) only account for plastics ≥ 300 µm in diameter. In addition, we surveyed 770 personal care products to determine the occurrence, concentration and size distribution of polyethylene microbeads. Particle concentrations ranged from 1.9 to 71.9 mg g-1 of product or 1649 to 31,266 particles g-1 of product. The large majority ( > 95%) of particles in products surveyed were less than the 300 µm minimum diameter, indicating that previous environmental surveys could be underestimating microplastic contamination. To account for smaller particles as well as microfibers from synthetic textiles, we strongly recommend that future surveys consider methods that materials < 300 µm in diameter.