MANP in Hypertension With Metabolic Syndrome: Proof-of-Concept Study of Natriuretic Peptide-Based Therapy for Cardiometabolic Disease.

Hypertension and metabolic syndrome frequently coexist to increase the risk for adverse cardiometabolic outcomes. To date, no drug has been proven to be effective in treating hypertension with metabolic syndrome. M-atrial natriuretic peptide is a novel atrial natriuretic peptide analog that activates the particulate guanylyl cyclase A receptor. This study conducted a double-blind, placebo-controlled trial in 22 patients and demonstrated that a single subcutaneous injection of M-atrial natriuretic peptide was safe, well-tolerated, and exerted pleiotropic properties including blood pressure-lowering, lipolytic, and insulin resistance-improving effects. (MANP in Hypertension and Metabolic Syndrome [MANP-HTN-MS]; NCT03781739).

UK guideline on the transition and management of childhood liver diseases in adulthood.

INTRODUCTION: Improved outcomes of liver disease in childhood and young adulthood have resulted in an increasing number of young adults (YA) entering adult liver services. The adult hepatologist therefore requires a working knowledge in diseases that arise almost exclusively in children and their complications in adulthood. AIMS: To provide adult hepatologists with succinct guidelines on aspects of transitional care in YA relevant to key disease aetiologies encountered in clinical practice. METHODS: A systematic literature search was undertaken using the Pubmed, Medline, Web of Knowledge and Cochrane database from 1980 to 2023. MeSH search terms relating to liver diseases ('cholestatic liver diseases', 'biliary atresia', 'metabolic', 'paediatric liver diseases', 'autoimmune liver diseases'), transition to adult care ('transition services', 'young adult services') and adolescent care were used. The quality of evidence and the grading of recommendations were appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. RESULTS: These guidelines deal with the transition of YA and address key aetiologies for the adult hepatologist under the following headings: (1) Models and provision of care; (2) screening and management of mental health disorders; (3) aetiologies; (4) timing and role of liver transplantation; and (5) sexual health and fertility. CONCLUSIONS: These are the first nationally developed guidelines on the transition and management of childhood liver diseases in adulthood. They provide a framework upon which to base clinical care, which we envisage will lead to improved outcomes for YA with chronic liver disease.

The Cardiorenal Effects of Chronic Phosphodiesterase-V Inhibition in Preclinical Diastolic Dysfunction (Stage B Heart Failure).

OBJECTIVE: To determine whether chronic phosphodiesterase-V (PDEV) inhibition with tadalafil will improve urinary sodium excretion, glomerular filtration rate (GFR), plasma cyclic guanosine 3', 5'-monophosphate (cGMP), and urinary cGMP excretion in response to volume expansion (VE) in patients with preclinical diastolic dysfunction (PDD) or stage B heart failure. BACKGROUND: PDD is defined as abnormal diastolic function with normal systolic function, without clinical heart failure. PDD is predictive of development of heart failure and all-cause mortality. Impaired renal function and attenuated cGMP response to VE are hallmarks of PDD. METHODS: A double-blind, placebo-controlled, proof-of-concept study was conducted to compare 12 weeks of tadalafil 20 mg daily (n = 14) vs placebo (n = 7). Subjects underwent 2 study visits 12 weeks apart. Renal, neurohormonal and echocardiographic assessments were performed before and after intravascular VE (normal saline 0.25 mL/kg/min for 1 hour). RESULTS: Baseline characteristics were similar. There was no increase in GFR, plasma cGMP or urinary cGMP excretion in response to VE in either group at visit 1. At visit 2, tadalafil did not result in significant change in GFR but increased plasma cGMP and urinary cGMP excretion at baseline. In response to VE, tadalafil resulted in increased urine flow, urinary sodium excretion, GFR (7.00 [-1.0, 26.3] vs -9.00 [-24.5, 2.0] mL/min/1.73m2; P = 0.02) and plasma cGMP (0.50 [-0.1, 0.7] vs -0.25 [-0.6, -0.1] pmol/mL; P = 0.02). It did not improve urinary cGMP excretion after VE. CONCLUSION: In PDD, chronic PDEV inhibition with tadalafil improved renal response to VE through increased urine flow, urinary sodium excretion, GFR, and plasma cGMP. Further studies are required to determine whether this enhanced renal response can mitigate progression to clinical heart failure.

Effects of phosphodiesterase V inhibition alone and in combination with BNP on cardiovascular and renal response to volume load in human preclinical diastolic dysfunction.

Preclinical diastolic dysfunction (PDD) results in impaired cardiorenal response to volume load (VL) which may contribute to the progression to clinical heart failure with preserved ejection fraction (HFpEF). The objective was to evaluate if phosphodiesterase V inhibition (PDEVI) alone or combination PDEVI plus B-type natriuretic peptide (BNP) administration will correct the impaired cardiorenal response to VL in PDD. A randomized double-blinded placebo-controlled cross-over study was conducted in 20 subjects with PDD, defined as left ventricular ejection fraction (LVEF) >50% with moderate or severe diastolic dysfunction by Doppler echocardiography and without HF diagnosis or symptoms. Effects of PDEVI with oral tadalafil alone and tadalafil plus subcutaneous (SC) BNP, administered prior to acute volume loading, were assessed. Tadalafil alone did not result in improvement in cardiac response to VL, as measured by LVEF, LV end diastolic volume, left atrial volume (LAV), or right ventricular systolic pressure (RVSP). Tadalafil plus SC BNP resulted in improved cardiac response to VL, with increased LVEF (4.1 vs. 1.8%, p = 0.08) and heart rate (4.3 vs. 1.6 bpm, p = 0.08), and reductions in both LAV (-4.3 ± 10.4 vs. 2.8 ± 6.6 ml, p = 0.03) and RVSP (-4.0 ± 3.0 vs. 2.1 ± 6.0 mmHg, p < 0.01) versus tadalafil alone. Plasma and urinary cyclic guanosine monophosphate (cGMP) excretion levels were higher (11.3 ± 12.3 vs. 1.7 ± 3.8 pmol/ml, 1851.0 ± 1386.4 vs. 173.4 ± 517.9 pmol/min, p < 0.01) with tadalafil plus SC BNP versus tadalafil alone. There was no improvement in renal response as measured by GFR, renal plasma flow, sodium excretion, and urine flow with tadalafil plus SC BNP compared to tadalafil alone. In subjects with PDD, tadalafil alone resulted in no improvement in cardiac adaptation, while tadalafil and SC BNP resulted in enhanced cardiac adaptation to VL. TRIAL REGISTRATION: ClinicalTrials.gov NCT01544998.

Prevalence of Transthyretin Amyloid Cardiomyopathy in Heart Failure With Preserved Ejection Fraction.

Importance: Heart failure (HF) with preserved ejection fraction (HFpEF) is common, is frequently associated with ventricular wall thickening, and has no effective therapy. Transthyretin amyloid cardiomyopathy (ATTR-CM) can cause the HFpEF clinical phenotype, has highly effective therapy, and is believed to be underrecognized. Objective: To examine the prevalence of ATTR-CM without and with systematic screening in patients with HFpEF and ventricular wall thickening. Design, Setting, and Participants: This population-based cohort study assessed ATTR-CM prevalence in 1235 consecutive patients in southeastern Minnesota with HFpEF both without (prospectively identified cohort study) and with (consenting subset of cohort study, n = 286) systematic screening. Key entry criteria included validated HF diagnosis, age of 60 years or older, ejection fraction of 40% or greater, and ventricular wall thickness of 12 mm or greater. In this community cohort of 1235 patients, 884 had no known ATTR-CM, contraindication to technetium Tc 99m pyrophosphate scanning, or other barriers to participation in the screening study. Of these 884 patients, 295 consented and 286 underwent scanning between October 5, 2017, and March 9, 2020 (community screening cohort). Exposures: Medical record review or technetium Tc 99m pyrophosphate scintigraphy and reflex testing for ATTR-CM diagnosis. Main Outcomes and Measures: The ATTR-CM prevalence by strategy (clinical diagnosis or systematic screening), age, and sex. Results: A total of 1235 patients participated in the study, including a community cohort (median age, 80 years; interquartile range, 72-87 years; 630 [51%] male) and a community screening cohort (n = 286; median age, 78 years; interquartile range, 71-84 years; 149 [52%] male). In the 1235 patients in the community cohort without screening group, 16 patients (1.3%; 95% CI, 0.7%-2.1%) had clinically recognized ATTR-CM. The prevalence was 2.5% (95% CI, 1.4%-4.0%) in men and 0% (95% CI, 0.0%-0.6%) in women. In the 286 patients in the community screening cohort, 18 patients (6.3%; 95% CI, 3.8%-9.8%) had ATTR-CM. Prevalence increased with age from 0% in patients 60 to 69 years of age to 21% in patients 90 years and older (P < .001). Adjusting for age, ATTR-CM prevalence differed by sex, with 15 of 149 men (10.1%; 95% CI, 5.7%-16.1%) and 3 of 137 women (2.2%; 95% CI, 0.4%-6.3%) having ATTR-CM (P = .002). Conclusions and Relevance: In this cohort study based in a community-based setting, ATTR-CM was present in a substantial number of cases of HFpEF with ventricular wall thickening, particularly in older men. These results suggest that systematic evaluation can increase the diagnosis of ATTR-CM, thereby providing therapeutically relevant phenotyping of HFpEF.

STOP-HF Trial: Higher Endogenous BNP and Cardiovascular Protection in Subjects at Risk for Heart Failure.

B-type natriuretic peptide (BNP) possesses blood-pressure-lowering, antifibrotic, and aldosterone-suppressing properties. In Stage A and B heart failure, the carriers of the minor C allele of the BNP genetic variant rs198389 have higher circulating levels of BNP and are at decreased risk of hypertension, new-onset left ventricular systolic dysfunction, and hospitalization for major adverse cardiovascular events. Future studies are warranted to investigate the role of BNP genetic testing and BNP-based therapy in the prevention of heart failure.

Sex-specific cut-off values for soluble suppression of tumorigenicity 2 (ST2) biomarker increase its cardiovascular prognostic value in the community.

BACKGROUND: Suppression of tumorigenicity 2 (ST2) has important cardiovascular prognostic value in community patients; however, previous analyses have utilized non-sex specific cut-off values. We assessed whether sex-specific ST2 cut-off values would improve the prognostic utility of ST2 in the asymptomatic community. METHODS: A total of 2042 participants underwent clinical assessment and echocardiographic evaluation. Baseline measurements of high sensitivity troponin, natriuretic peptides and ST2 were obtained in 1681 individuals. ST2, cardiac biomarkers and associated co-morbidities were evaluated by sex-specific ST2 quartile analysis. ST2 concentrations were also analysed as dichotomous variables defined as being above the sex-specific cut-off for each the outcomes of heart failure (HF), major adverse cardiac event (MACE) and mortality. RESULTS: Median ST2 concentration was 29.4 ng/mL in male subjects and 24.1 ng/mL in female subjects. Higher ST2 concentrations were associated with incident HF (p<0.001; preserved ejection fraction (EF) p<0.001, reduced EF p=0.23), MACE (p=0.003) and mortality (p<0.001) across sex-specific quartiles. Event-based, hazard ratio (HR) analysis revealed sex-specific ST2 cut-offs were significantly more predictive of incident HF, MACE and mortality compared to non-sex-specific analysis even following adjustment for cardiac co-morbidities and traditional biomarkers. CONCLUSIONS: These data suggest that sex-specific cut-offs, greater than non-sex specific cut-offs, significantly impact the prognostic value of the biomarker ST2 in the asymptomatic community cohort.Clinical SignificanceSuppression of tumorigenicity 2 (ST2) is a biomarker which has known associations with heart failure (HF), major adverse cardiac events (MACEs) and mortality in the general population.Recent data support the concept of sex-specific cut off values and individualized approaches based on sex to predict cardiovascular disease. Given the difference in pathobiology between the sexes, the fact that such approaches improve risk stratification is understandable. Thus, when sex-specific treatments are developed, this may similarly lead to improved outcomes.The use of sex-specific ST2 cut-off values significantly improved the prognostic value in predicting HF, MACE, and mortality in an asymptomatic community. This prognostication was particularly strong for HF with preserved ejection fraction and remained clinically significant following adjustment for cardiac co-morbidities and other traditional cardiac biomarkers (NTproBNP and hscTnI).

Artificial Intelligence-Augmented Electrocardiogram Detection of Left Ventricular Systolic Dysfunction in the General Population.

OBJECTIVE: To validate an artificial intelligence-augmented electrocardiogram (AI-ECG) algorithm for the detection of preclinical left ventricular systolic dysfunction (LVSD) in a large community-based cohort. METHODS: We identified a randomly selected community-based cohort of 2041 subjects age 45 years or older in Olmsted County, Minnesota. All participants underwent a study echocardiogram and ECG. We first assessed the performance of the AI-ECG to identify LVSD (ejection fraction ≤40%). After excluding participants with clinical heart failure, we further assessed the AI-ECG to detect preclinical LVSD among all patients (n=1996) and in a high-risk subgroup (n=1348). Next we modelled an imputed screening program for preclinical LVSD detection where a positive AI-ECG triggered an echocardiogram. Finally, we assessed the ability of the AI-ECG to predict future LVSD. Participants were enrolled between January 1, 1997, and September 30, 2000; and LVSD surveillance was performed for 10 years after enrollment. RESULTS: For detection of LVSD in the total population (prevalence, 2.0%), the area under the receiver operating curve for AI-ECG was 0.97 (sensitivity, 90%; specificity, 92%); in the high-risk subgroup (prevalence 2.7%), the area under the curve was 0.97 (sensitivity, 92%; specificity, 93%). In an imputed screening program, identification of one preclinical LSVD case would require 88.3 AI-ECGs and 8.7 echocardiograms in the total population and 65.7 AI-ECGs and 5.5 echocardiograms in the high-risk subgroup. The unadjusted hazard ratio for a positive AI-ECG for incident LVSD over 10 years was 2.31 (95% CI, 1.32 to 4.05; P=.004). CONCLUSION: Artificial intelligence-augmented ECG can identify preclinical LVSD in the community and warrants further study as a screening tool for preclinical LVSD.

Synchronous neurology-primary care collaboration in a medical home.

BACKGROUND: Synchronous collaboration as defined by a simultaneous encounter between primary care providers (PCPs), patients, and neurologists may improve access to neurologic expertise, care value, and satisfaction of PCPs and patients. We examined a series of synchronous collaborations and report outcomes, PCP satisfaction, downstream utilization, and illustrative case examples. METHODS: Within an outpatient collaborative primary care-neurology care model, we implemented synchronous video consultations from a central hub to satellite clinics while increasing availability of synchronous telephone and face-to-face collaboration. PCP experience was assessed by a postcollaboration survey. Individual cases were summarized. Clinical and utilization outcomes were assessed by a neurologist immediately after and by follow-up chart review. RESULTS: A total of 58 total synchronous collaborations were performed: 30 by telephone (52%), 18 face to face (31%), and 10 by video (17%) over 27 clinic half-days. The most frequent outcomes as assessed by the neurologist were reassurance of the PCP (23/58; 40%) and patient (22/59; 38%), and the neurologist changed the treatment plan (23/58; 40%). A subsequent face-to-face consultation was completed in 15% (6/58) of patients initially assessed by telephone or video. Test utilization was avoided in 40% (23/58). Unintended utilization occurred 9% (5/58). Most PCPs were very satisfied with the ease of access, quality of care, and reported high likelihood of subsequent use. PCPs perceived similar or less time spent during synchronous vs asynchronous collaboration and neurologist usually altered the testing (87.8%) and treatment plan (95.2%). CONCLUSIONS: Synchronous collaboration between neurologists and PCPs may improve timely access to neurologic expertise, downstream utilization, and PCP satisfaction.

An exploratory study of the experiences of deceased-donor liver transplant recipients and their need for psychotherapeutic support.

AIMS AND OBJECTIVES: This study aimed to explore the experiences of liver transplant recipients during their journey through the treatment and their need for psychotherapeutic support related to this process. BACKGROUND: Over time, measures of survival and quality of life in liver transplant recipients have continued to improve but their emotional needs remain under explored. In the longer-term recovery from transplantation, the focus shifts from physical health to psychological health. In the UK, there are no known embedded adult psychological services in liver transplant centres to react to this need. DESIGN: A qualitative descriptive design was used. METHODS: Grounded theory analysis was used to study the narratives of six adult liver transplant recipients. Through a process of coding, conceptual categories were established to describe the participant experiences. The study adhered to the EQUATOR checklist, SRQR. RESULTS: Four categories emerged that were related to the experience of liver transplantation for the recipients. These were a process of adjustment, the phenomenon of waiting, liver transplant as a transformative experience and on the value of support. The participants identified a lack of psychotherapeutic support provided by the liver transplant service and felt that an embedded psychotherapeutic service would promote accessing such support during challenging times. CONCLUSION: Through the process of liver transplantation, recipients experience challenges with adjustment, waiting, feeling transformed and they value support with these feelings. In correlation with other studies, the findings of this study highlight the need for providing psychotherapeutic support within liver transplant services. RELEVANCE TO CLINICAL PRACTICE: The study provides evidence to support recommendations for a conjoined psychotherapy service within liver transplant services to support patients with their holistic needs.

Computerized Advisory Decision Support for Cardiovascular Diseases in Primary Care: A Cluster Randomized Trial.

PURPOSE: The purpose of this research was to evaluate the impact of an outpatient computerized advisory clinical decision support system (CDSS) on adherence to guideline-recommended treatment for heart failure, atrial fibrillation, and hyperlipidemia. METHODS: Twenty care teams (109 clinicians) in a primary care practice were cluster-randomized to either access or no access to an advisory CDSS integrated into the electronic medical record. For patients with an outpatient visit, the CDSS determined if they had heart failure with reduced ejection fraction, hyperlipidemia, or atrial fibrillation; and if so, was the patient receiving guideline-recommended treatment. In the intervention group, an alert was visible in the medical record if there was a discrepancy between current and guideline-recommended treatment. Clicking the alert displayed the treatment discrepancy and recommended treatment. Outcomes included prescribing patterns, self-reported use of decision aids, and self-reported efficiency. The trial was conducted between May 1 and November 15, 2016, and incorporated 16,310 patient visits. RESULTS: The advisory CDSS increased adherence to guideline-recommended treatment for heart failure (odds ratio [OR] 7.6, 95% confidence interval [CI], 1.2, 47.5) but had no impact in atrial fibrillation (OR 0.94, 95% CI 0.15, 5.94) or hyperlipidemia (OR 1.1, 95% CI 0.6, 1.8). Clinicians with access to the CDSS self-reported greater use of risk assessment tools for heart failure (3.6 [1.1] vs 2.7 [1.0], mean [standard deviation] on a 5-point scale) but not for atrial fibrillation or hyperlipidemia. The CDSS did not impact self-assessed efficiency. The overall usage of the CDSS was low (19%). CONCLUSIONS: A computerized advisory CDSS improved adherence to guideline-recommended treatment for heart failure but not for atrial fibrillation or hyperlipidemia.

A Contemporary Systematic Approach to Assessing the Patient with Heart Failure with Reduced Ejection Fraction: Multimodal Noninvasive and Invasive Evaluation.

Heart failure with reduced ejection fraction (HFrEF) is a progressive clinical syndrome commonly associated with left ventricle dilatation and characterized by reduced cardiac output, secondary pulmonary and systemic venous congestion, and inadequate peripheral oxygen delivery. It is common yet complex and requires synthesis of evidence-based guidelines along with strong clinical acumen. The following is a review of an illustrative case that highlights the important clinical considerations in diagnosis, assessment, and management of HFrEF commonly encountered in practice. Explanations provided highlight of the relevant pathophysiology of HFrEF as well as detailed explanations of interpretation of examinations and both noninvasive and invasive assessment in heart failure. The example provided would hopefully serve as a potential point of reference for trainees as well as healthcare practitioners for patients with HFrEF.

Screening for cardiac contractile dysfunction using an artificial intelligence-enabled electrocardiogram.

Asymptomatic left ventricular dysfunction (ALVD) is present in 3-6% of the general population, is associated with reduced quality of life and longevity, and is treatable when found1-4. An inexpensive, noninvasive screening tool for ALVD in the doctor's office is not available. We tested the hypothesis that application of artificial intelligence (AI) to the electrocardiogram (ECG), a routine method of measuring the heart's electrical activity, could identify ALVD. Using paired 12-lead ECG and echocardiogram data, including the left ventricular ejection fraction (a measure of contractile function), from 44,959 patients at the Mayo Clinic, we trained a convolutional neural network to identify patients with ventricular dysfunction, defined as ejection fraction ≤35%, using the ECG data alone. When tested on an independent set of 52,870 patients, the network model yielded values for the area under the curve, sensitivity, specificity, and accuracy of 0.93, 86.3%, 85.7%, and 85.7%, respectively. In patients without ventricular dysfunction, those with a positive AI screen were at 4 times the risk (hazard ratio, 4.1; 95% confidence interval, 3.3 to 5.0) of developing future ventricular dysfunction compared with those with a negative screen. Application of AI to the ECG-a ubiquitous, low-cost test-permits the ECG to serve as a powerful screening tool in asymptomatic individuals to identify ALVD.

Cardiac Versus Renal Response to Volume Expansion in Preclinical Systolic Dysfunction With PDEV Inhibition and BNP.

Impaired cardiorenal response to acute saline volume expansion in preclinical systolic dysfunction (PSD) may lead to symptomatic heart failure. The objective was to determine if combination phosphodiesterase-V inhibition and exogenous B-type natriuretic peptide (BNP) administration may enhance cardiorenal response. A randomized double-blinded, placebo-controlled study was conducted in 21 subjects with PSD and renal dysfunction. Pre-treatment with tadalafil and subcutaneous BNP resulted in improved cardiac function, as evidenced by improvement in ejection fraction, left atrial volume index, and left ventricular end-diastolic volume. However, there was reduced renal response with reduction in renal plasma flow, glomerular filtration rate, and urine flow. (Tadalafil and Nesiritide as Therapy in Pre-clinical Heart Failure; NCT01544998).

Getting to the Heart of the Matter: A Triage Model to Improve Utilization of Cardiology Consultative Services.

OBJECTIVE: To assess the impact of a triage system of emergency department (ED) referrals for outpatient cardiology appointments. PATIENT AND METHODS: We implemented a triage system of ED referrals for outpatient cardiology appointments among patients with a cardiovascular chief complaint deemed safe to leave the ED but needing outpatient follow-up. There were 303 and 267 unique patients in the pre-triage implementation and post-triage implementation cohorts, respectively. We collected retrospective billing data to assess ED return visits, hospitalizations, cardiology outpatient visits, and cardiovascular testing. The pre-triage implementation cohort included patients with an ED visit date between January 1, 2014, and December 31, 2014. The post-triage implementation cohort included patients with an ED visit date between July 1, 2015, and June 30, 2016. RESULTS: The triage model reduced the number of ED-referred cardiovascular service appointments by 73.0% (195 of 267 patients). Additionally, the "no-show" rate for appointments decreased from 17.8% (54 of 303 patients) to 7.9% (21 of 267 patients). There was no increase in ED return visits or unplanned hospitalizations in the posttriage cohort. Finally, the triage model was not associated with an increase in resource-intensive cardiovascular testing (eg, imaging stress tests or computed tomography). CONCLUSION: Triage of ED referrals for outpatient cardiovascular service appointments reduced cardiology appointment utilization with no impact on return ED visits, hospitalizations, or cardiovascular testing.

Neuroimaging utilization and findings in headache outpatients: Significance of red and yellow flags.

Background Neuroimaging for headache commonly exceeds published guideline recommendations and may be overutilized. Methods We conducted a retrospective cross-sectional study of all outpatient community patients at Mayo Clinic Rochester who underwent a neuroimaging study for a headache indication in 2015. We assessed the neuroimaging utilization pattern, clinical application of red flags, and concordance with neuroimaging guidelines. Results We identified 190 outpatients who underwent 304 neuroimaging studies for headache. The median age was 46.5 years (range 18-91 years), 65% were female, and most reported no prior history of headache (n = 97, 51%). A minority of patients had prior brain imaging studies (n = 44, 23%) and neurological consultations for headache (n = 29, 15%). Few studies were ordered after consultation with a neurologist (n = 14, 7%). Seventy-seven percent of patients were documented to have a "red flag" justifying the imaging study. Abnormal neuroimaging findings were found in 3.1% of patients with warning flags (5/161); carotid dissection (n = 3) and reversible cerebral vasoconstrictive syndrome (n = 2). An estimated 35% of patients were imaged against guidelines. Conclusions The prevalence of serious causes of headache in a community practice was low despite the presence of a documented red flag symptom. Inadequate understanding or application of red flags may be contributing to recommendations to image patients against current guidelines. Interventions to reduce unnecessary neuroimaging of patients with headache need to be designed and implemented.

Hemodynamic factors associated with serum chloride in ambulatory patients with advanced heart failure.

BACKGROUND: Lower serum chloride (Cl) is associated with mortality in heart failure patients and may be more prognostically relevant than sodium. However, the association of hemodynamics and Cl levels is unknown. METHODS: 438 sequential patients with advanced chronic heart failure (ACHF) underwent invasive hemodynamic assessment with measured serum Cl levels during an evaluation for ACHF. Patients were followed for death, heart transplant (HT), or ventricular assist device placement (VAD). A backwards regression model determined hemodynamic predictors of Cl (removal, P<0.1) with candidate variables: Fick cardiac index (FCI), pulmonary capillary wedge pressure (PCWP), right atrial pressure (RAP), mean arterial pressure (MAP), heart rate (HR), and pulmonary artery systolic pressure (PASP). All models were also adjusted for serum sodium and bicarbonate. RESULTS: In this cohort, the median Cl level was 102 [98-104]meq/L (range 86-113meq/L). Chloride was weakly correlated with FCI (rho 0.12, P=0.01) and MAP (rho 0.21, P<0.001); but not PCWP, RAP, HR or PASP (P>0.05 for all). In the multivariable model, FCI (beta 0.73meq/L/L/min/m2, P=0.002) but not RAP (P=0.3) or MAP (P=0.2), remained associated with Cl. Lower Cl was associated with increased risk of death, HT, or VAD placement (HR 0.94/meq/L, 95% CI 0.89-0.99, P=0.01). However, this association was attenuated after additional adjustment for BUN (P=0.27) and PCWP and FCI (0.48). CONCLUSIONS: Lower FCI, not lower MAP or higher cardiac filling pressures, was associated with lower chloride. Although lower chloride was associated with poor long-term outcomes, this risk attenuates with adjustment for more conventional clinical parameters.

Impact of electronic clinical decision support on adherence to guideline-recommended treatment for hyperlipidaemia, atrial fibrillation and heart failure: protocol for a cluster randomised trial.

INTRODUCTION: Clinical practice guidelines facilitate optimal clinical practice. Point of care access, interpretation and application of such guidelines, however, is inconsistent. Informatics-based tools may help clinicians apply guidelines more consistently. We have developed a novel clinical decision support tool that presents guideline-relevant information and actionable items to clinicians at the point of care. We aim to test whether this tool improves the management of hyperlipidaemia, atrial fibrillation and heart failure by primary care clinicians. METHODS/ANALYSIS: Clinician care teams were cluster randomised to receive access to the clinical decision support tool or passive access to institutional guidelines on 16 May 2016. The trial began on 1 June 2016 when access to the tool was granted to the intervention clinicians. The trial will be run for 6 months to ensure a sufficient number of patient encounters to achieve 80% power to detect a twofold increase in the primary outcome at the 0.05 level of significance. The primary outcome measure will be the percentage of guideline-based recommendations acted on by clinicians for hyperlipidaemia, atrial fibrillation and heart failure. We hypothesise care teams with access to the clinical decision support tool will act on recommendations at a higher rate than care teams in the standard of care arm. ETHICS AND DISSEMINATION: The Mayo Clinic Institutional Review Board approved all study procedures. Informed consent was obtained from clinicians. A waiver of informed consent and of Health Insurance Portability and Accountability Act (HIPAA) authorisation for patients managed by clinicians in the study was granted. In addition to publication, results will be disseminated via meetings and newsletters. TRIAL REGISTRATION NUMBER: NCT02742545.