Implementation of an interdisciplinary tracheostomy care protocol to decrease rates of tracheostomy-related pressure ulcers and injuries.

OBJECTIVES: Tracheostomy-related pressure injuries (TRPI) have been demonstrated to occur in approximately 10% of tracheostomy patients. In this study, we present TRPI outcomes after implementation of a standardized tracheostomy care protocol. METHODS: A tracheostomy care protocol was developed by an interdisciplinary quality improvement program and implemented on July 1, 2016. The protocol was designed to minimize factors that contribute to the development of TRPI. Rates of TRPI over the subsequent 20 months were compared to the year before implementation. RESULTS: 9 out of 85 patients (10.6%) developed TRPI in the pre-protocol cohort compared to 0 of 137 (0%) in the post-protocol cohort, which was a statistically significant decrease by Fisher's exact test with a p-value of 0.0001. Pearson's correlation coefficient demonstrated a negative correlation between age and post-operative day of diagnosis (r = -0.641, p = 0.063), indicating that older patients develop TRPI more quickly. CONCLUSIONS: Interdisciplinary peri-operative tracheostomy care protocols can be effective in decreasing rates of TRPI.

Team-Based Intervention to Reduce the Impact of Nonactionable Alarms in an Adult Intensive Care Unit.

BACKGROUND: Nonactionable alarms comprise over 70% of alarms and contribute a threat to patient safety. Few studies have reported approaches to translate and sustain these interventions in clinical settings. PURPOSE: This study tested whether an interprofessional team-based approach can translate and implement effective alarm reduction interventions in the adult intensive care unit. METHODS: The study was a prospective, cohort, pre- and postdesign with repeated measures at baseline (preintervention) and post-phase I and II intervention periods. The settings for the most prevalent nonactionable arrhythmia and bedside parameter alarms were adjusted during phases I and II, respectively. RESULTS: The number of total alarms was reduced by 40% over a 14-day period after both intervention phases were implemented. The most prevalent nonactionable parameter alarms decreased by 47% and arrhythmia alarms decreased by 46%. CONCLUSIONS: It is feasible to translate and sustain system-level alarm management interventions addressing alarm fatigue using an interprofessional team-based approach.

A Health System's Pilot Experience with Using Social Knowledge Networking (SKN) Technology to Enable Meaningful Use of EHR Medication Reconciliation Technology.

Similar to issues faced in health systems across USA, AU Health, based in Augusta, Georgia, faced a scenario of low physician engagement in, and limited-use of its Electronic Health Record (EHR) Medication Reconciliation (MedRec) technology, which translated to high rates of medication discrepancies and low accuracy of the patient's active medication list, during transitions of care. In fall 2016, a two-year grant was secured from the U.S. Agency for Healthcare Research and Quality (AHRQ), to pilot a Social Knowledge Networking (SKN) system pertaining to "EHR-MedRec," to enable AU Health to progress from "limited use" of EHR MedRec technology, to "meaningful use." The rationale behind an SKN system, is that it could provide a platform for inter-professional knowledge exchange on practice issues related to EHR MedRec, across diverse provider subgroups and care settings, to highlight adverse consequences of gaps in practice for patient safety, and emphasize the value of adhering to best-practices in EHR MedRec. This, in turn, is expected to increase provider engagement in addressing issues related to EHR MedRec, and promote inter-professional learning of best-practices, to create a foundation for practice change or improvement (e.g., Meaningful Use of EHR MedRec technology). This Case Report describes AU Health's experiences with this novel initiative to pilot an SKN system for enabling Meaningful Use of EHR MedRec technology. It also discusses lessons learned in regard to the potential of an SKN system to enable inter-professional learning and practice improvement in the context of EHR MedRec, which, in turn, helps identify strategies and practice implications for healthcare managers.

A qualitative study of interprofessional learning related to electronic health record (EHR) medication reconciliation within a social knowledge networking (SKN) system.

Background: Similar to issues faced in health systems across the USA, AU Health faced a scenario of low physician engagement in and limited use of its Electronic Health Record (EHR) Medication Reconciliation (MedRec) technology, which translated to high rates of medication discrepancies and low accuracy of the patient's active medication list, during transitions of care. In fall 2016, a 2-year research grant was secured to pilot a Social Knowledge Networking (SKN) system on "EHR MedRec" to enable AU Health to progress from "limited use" of EHR MedRec technology to "meaningful use." Purpose: The aims of this study were to 1) examine dynamics of interprofessional knowledge exchange and learning related to EHR MedRec on the SKN system and 2) explore associations between "SKN Use" and "Meaningful Use (MU) of EHR MedRec," with the latter being assessed in terms of adherence to best practices in EHR MedRec. Methods: Over a 1-year period, 50 SKN Users (practitioners from inpatient and outpatient medicine settings), participated in discussing issues related to EHR MedRec, moderated by five SKN Moderators (senior administrators). Qualitative analysis was used to understand dynamics of interprofessional knowledge exchange and descriptive analysis was used to examine trends in two measures of MU of EHR MedRec, identified for the study. Results: Interprofessional knowledge exchanges related to EHR MedRec on the SKN system, progressed from "problem statements" to "problem-solving statements" to "IT system education" to "best-practice assertions" to "culture change assertions" to "collective learning (aha) moments" to lay a foundation for practice change. These interprofessional learning dynamics were associated with distinct improvement trends in both measures of MU of EHR MedRec technology. Conclusion: Results suggest that an SKN system could be a valuable tool in enabling MU of EHR MedRec technology. The study helps identify strategies for the creation of "learning health systems," to enable successful change implementation in healthcare organizations.

A Mixed-Method Study of Practitioners' Perspectives on Issues Related to EHR Medication Reconciliation at a Health System.

BACKGROUND: In an effort to reduce medication discrepancies during transitions of care and improve accuracy of the patient's medication list, AU Health conducted a study to identify a comprehensive set of issues related to electronic health record (EHR) medication reconciliation (MedRec) from the perspective of practitioners directly involved in the EHR MedRec process. METHODS: An exploratory mixed-method design was used. The 2-round study included 15 individual interviews, followed by a survey of 200 practitioners (ie, physicians, nurses, and pharmacists) based in the outpatient and inpatient medicine service at AU Health. RESULTS: Thematic analysis of interview data identified 55 issue items related to EHR MedRec under 9 issue categories. The survey sought practitioners' importance rating of all issue items identified from interviews. A total of 127 (63%) survey responses were received. Factor analysis served to validate the following 6 of the 9 issue categories, all of which were rated "important" or higher (on average), by over 70% of all respondents: (1) care coordination (CCI); (2) patient education (PEI); (3) ownership and accountability (OAI); (4) processes-of-care (PCI); (5) IT-related (ITRI); and (6) workforce training (WTI). Significance testing of importance rating by professional affiliation revealed no statistically significant differences for CCI and PEI, and some statistically significant differences for OAI, PCI, ITRI, and WTI. CONCLUSION: There were 2 key gleanings from the issues related to EHR MedRec unearthed by this study: (1) there was an absence of shared understanding among practitioners, of the value of EHR MedRec in promoting patient safety, which contributed to workarounds, and suboptimal use of the EHR MedRec system; and (2) there was a sociotechnical dimension to many of the issues, creating an added layer of complexity. These gleanings, in turn, provide insights into best practices for managing both (1) clinical transitions of care in the EHR MedRec process and (2) sociotechnical challenges encountered in EHR MedRec implementation.

A Health System's Pilot Experience with Using Mobile Social Knowledge Networking (SKN) Technology to Enable Meaningful Use of EHR Medication Reconciliation Technology.

In fall 2016, a two-year grant was secured from AHRQ, to pilot a mobile Social Knowledge Networking (SKN) system on Electronic Health Record (EHR) Medication Reconciliation (MedRec), to enable Augusta University (AU) Health System, to progress from "limited-use" of EHR-MedRec technology, to "meaningful-use." The rationale is that an SKN system would enable knowledge exchange on practice issues related to EHR-MedRec, across diverse provider subgroups and settings-of-care, which, in turn, is expected to increase provider engagement, promote inter-professional learning of best-practices, and provide a foundation for practice change (e.g., Meaningful Use of EHR-MedRec technology). Over a one-year period, 50 SKN Users (physicians, nurses, and pharmacists from outpatient-and-inpatient-medicine services), participated in discussing issues-related-to-EHR-MedRec, moderated by 5 SKN Moderators (senior administrators). This paper describes the health system's experiences with this pilot initiative; and discusses lessons learned, in regard to the potential of a mobile SKN system to enable Meaningful Use of EHR-MedRec technology.

Creating a foundation for implementing an electronic health records (EHR)-integrated Social Knowledge Networking (SKN) system on medication reconciliation.

Background: In fall 2016, Augusta University received a two-year grant from AHRQ, to implement a Social Knowledge Networking (SKN) system for enabling its health system, AU-Health, to progress from "limited use" of EHR Medication Reconciliation (MedRec) Technology, to "meaningful use." Phase 1 sought to identify a comprehensive set of issues related to EHR MedRec encountered by practitioners at AU-Health. These efforts helped develop a Reporting Tool, which, along with a Discussion Tool, was incorporated into the AU-Health EHR, at the end of Phase 1. Phase 2 (currently underway), comprises a 52-week pilot of the EHR-integrated SKN system in outpatient and inpatient medicine units. The purpose of this paper is to describe the methods and results of Phase 1. Methods: Phase 1 utilized an exploratory mixed-method approach, involving two rounds of data collection. This included 15 individual interviews followed by a survey of 200 practitioners, i.e., physicians, nurses, and pharmacists, based in the outpatient and inpatient medicine service at AU Health. Results: Thematic analysis of interviews identified 55 issue-items related to EHR MedRec under 9 issue-categories. The survey sought practitioners' importance-rating of all issue-items identified from interviews. A total of 127 (63%) survey responses were received. Factor analysis served to validate the following 6 of the 9 issue-categories, all of which, were rated "Important" or higher (on average), by over 70% of all respondents: 1) Care-Coordination (CCI); 2) Patient-Education (PEI); 3) Ownership-and-Accountability (OAI); 4) Processes-of-Care (PCI); 5) IT-Related (ITRI); and 6) Workforce-Training (WTI). Significance-testing of importance-rating by professional affiliation revealed no statistically significant differences for CCI and PEI; and some statistically significant differences for OAI, PCI, ITRI, and WTI. Conclusion: There were two key gleanings from the issues related to EHR MedRec unearthed by this study: 1) there was an absence of shared understanding among practitioners, of the value of EHR MedRec in promoting patient safety, which contributed to workarounds, and suboptimal use of the EHR MedRec system; and 2) there was a socio-technical dimension to many of the issues, creating an added layer of complexity. These gleanings in turn, provide insights into best practices for managing both clinical transitions-of-care in the EHR MedRec process; and socio-technical challenges encountered in EHR MedRec implementation.

Systematic review of non-invasive cardiovascular imaging in the diagnosis of constrictive pericarditis.

BACKGROUND: Diagnosis of constrictive pericarditis (CP) can be challenging. It can be nearly impossible to distinguish CP from other causes of right heart failure. Although various imaging modalities help in the diagnosis, no test is definitive. Several reviews have addressed the role of various imaging techniques in the diagnosis of CP but a systematic review has not yet been published. OBJECTIVE: Our intention was to study the ability of various non-invasive imaging modalities to diagnose CP in patients with surgically confirmed disease and to apply our findings to develop a clinically useful diagnostic algorithm. METHODS: A PubMed (NLM) search was performed with MeSH term "constrictive pericarditis". Original articles that investigated the ability of various cardiovascular imaging modalities to noninvasively diagnose surgically confirmed CP were included in our review. Investigations that included any cases without surgical confirmation were excluded. RESULTS: The PubMed search yielded 3001 results with MeSH term "constrictive pericarditis" (January 8, 2016). We identified (40) studies on CP that matched our inclusion criteria. We summarized our results sorted by individual non-invasive CV imaging modalities - echocardiography, cardiac computed tomography (CT), and magnetic resonance imaging (MRI). Under each imaging modality, we grouped our discussion based on different parameters useful in CP diagnosis. CONCLUSIONS: In conclusion, contemporary diagnosis of CP is based on clinical features and echocardiography. Cardiac MRI is recommended in patients where echocardiography is not diagnostic. Both cardiac MRI and CT can guide surgical planning but we prefer MRI as it provides both structural and functional information.

Acute aerobic exercise differentially alters acylated ghrelin and perceived fullness in normal-weight and obese individuals.

Adiposity alters acylated ghrelin concentrations, but it is unknown whether adiposity alters the effect of exercise and feeding on acylated ghrelin responses. Therefore, the purpose of this study was to determine whether adiposity [normal-weight (NW) vs. obese (Ob)] influences the effect of exercise and feeding on acylated ghrelin, hunger, and fullness. Fourteen NW and 14 Ob individuals completed two trials in a randomized counterbalanced fashion, including a prior exercise trial (EX) and a no exercise trial (NoEX). During the EX trial, the participants performed 1 h of treadmill walking (55-60% peak O2 uptake) during the evening, 12 h before a 4-h standardized mixed meal test. Frequent blood samples were taken and analyzed for acylated ghrelin, and a visual analog scale was used to assess perceived hunger and fullness. In NW individuals, EX, compared with NoEX, reduced fasting acylated ghrelin concentrations by 18% (P = 0.03), and, in response to feeding, the change in acylated ghrelin (P = 0.02) was attenuated by 39%, but perceived hunger and fullness were unaltered. In Ob individuals, despite no changes in fasting or postprandial acylated ghrelin concentrations with EX, postprandial fullness was attenuated by 46% compared with NoEX (P = 0.05). In summary, exercise performed the night before a meal suppresses acylated ghrelin concentrations in NW individuals without altering perceived hunger or fullness. In Ob individuals, despite no changes in acylated ghrelin concentrations, EX reduced the fullness response to the test meal. Acylated ghrelin and perceived fullness responses are differently altered by acute aerobic exercise in NW and Ob individuals.

Resolution of an intracardiac mass with chemotherapy.

Right atrial intracardiac tumours are uncommonly seen during echocardiography. Our patient presented with primary mediastinal large B-cell lymphoma with intracardiac involvement. The tumour was seen by echocardiography and the extent of the tumour was defined by CT scan of the chest. Following chemotherapy directed to her specific tumour cell type, there was complete resolution of the intracardiac mass.

Prior exercise and postprandial incretin responses in lean and obese individuals.

PURPOSE: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) help regulate postprandial triacylglycerol (TAG) and insulin concentrations, but the effects of acute aerobic exercise on GLP-1 or GIP responses are unclear. The purpose of this study was to determine whether reductions in postprandial TAG and insulin with exercise are associated with GLP-1 and GIP responses. METHODS: Thirteen normal-weight (NW) and 13 obese (Ob) individuals participated in two, 4-d trials in random order including an exercise (EX) and a no exercise (NoEX) trial. Diet was controlled during both trials. The EX trial consisted of 1 h of treadmill walking (55%-60% of V˙O2peak) during the evening of day 3 of the trial, 12 h before a 4-h mixed meal test on day 4, during which frequent blood samples were collected to assess postprandial lipemia, glycemia, insulin, C-peptide, GIP, and GLP-1 responses. Insulin secretion was estimated using the insulinogenic index, and insulin clearance was estimated using the ratio of insulin to C-peptide. RESULTS: Postprandial TAG were 29% lower after EX in Ob individuals (P < 0.05) but were not significantly altered in NW individuals (P > 0.05). The drop in postprandial HDL cholesterol was attenuated with EX in Ob individuals (P < 0.05). Insulin responses were 14% lower after EX in Ob individuals (P < 0.05), and this was associated with reduced insulin secretion (P < 0.05), with no change in insulin clearance (P > 0.05). Glucose, C-peptide, GIP, and GLP-1 were not different between trials. CONCLUSION: A 1-h bout of moderate-intensity aerobic exercise the night before a mixed meal attenuates TAG and insulin responses in Ob but not NW individuals, an effect not associated with altered GLP-1 or GIP responses.

Simvastatin impairs exercise training adaptations.

OBJECTIVES: This study sought to determine if simvastatin impairs exercise training adaptations. BACKGROUND: Statins are commonly prescribed in combination with therapeutic lifestyle changes, including exercise, to reduce cardiovascular disease risk in patients with metabolic syndrome. Statin use has been linked to skeletal muscle myopathy and impaired mitochondrial function, but it is unclear whether statin use alters adaptations to exercise training. METHODS: This study examined the effects of simvastatin on changes in cardiorespiratory fitness and skeletal muscle mitochondrial content in response to aerobic exercise training. Sedentary overweight or obese adults with at least 2 metabolic syndrome risk factors (defined according to National Cholesterol Education Panel Adult Treatment Panel III criteria) were randomized to 12 weeks of aerobic exercise training or to exercise in combination with simvastatin (40 mg/day). The primary outcomes were cardiorespiratory fitness and skeletal muscle (vastus lateralis) mitochondrial content (citrate synthase enzyme activity). RESULTS: Thirty-seven participants (exercise plus statins: n = 18; exercise only: n = 19) completed the study. Cardiorespiratory fitness increased by 10% (p < 0.05) in response to exercise training alone, but was blunted by the addition of simvastatin resulting in only a 1.5% increase (p < 0.005 for group by time interaction). Similarly, skeletal muscle citrate synthase activity increased by 13% in the exercise-only group (p < 0.05), but decreased by 4.5% in the simvastatin-plus-exercise group (p < 0.05 for group-by-time interaction). CONCLUSIONS: Simvastatin attenuates increases in cardiorespiratory fitness and skeletal muscle mitochondrial content when combined with exercise training in overweight or obese patients at risk of the metabolic syndrome. (Exercise, Statins, and the Metabolic Syndrome; NCT01700530).

Utilization of phase II cardiac rehabilitation in Veterans Administration patients.

Cardiac rehabilitation (CR) is underutilized across the United States. Reported national average varies from 14-35% after acute myocardial infraction and 31% after coronary artery bypass grafting surgery. No study to date has examined the utilization of CR in eligible veteran population. In this retrospective study, computerized veteran medical records at a single Veterans Administration (VA) hospital were screened between January 1, 2006 and December 31, 2009. Patients who met the inclusion and exclusion criteria were surveyed telephonically and asked a series of questions relating to delivery and utilization of phase II CR. Data was collected using a pre-printed questionnaire and patient responses were number coded. Utilization rate of phase II CR in veterans was noted to be 21%. Common reasons reported for underutilization of CR included time and distance problems, orthopedic- and stroke-related muscle weakness and lack of motivation. Participation in Phase II CR led to better adherence to exercise long term. Also, 65-70% of the veterans expressed interest in a tailored home based CR program. CR is underutilized in eligible veterans. Compliance could possibly be improved if the veterans were offered a tailored CR program.

Meal frequency differentially alters postprandial triacylglycerol and insulin concentrations in obese women.

OBJECTIVE: The aim of this study was to compare postprandial lipemia, oxidative stress, antioxidant activity, and insulinemia between a three and six isocaloric high-carbohydrate meal frequency pattern in obese women. DESIGN AND METHODS: In a counterbalanced order, eight obese women completed two, 12-h conditions in which they consumed 1,500 calories (14% protein, 21% fat, and 65% carbohydrate) either as three 500 calorie liquid meals every 4-h or six 250 calorie liquid meals every 2-h. Blood samples were taken every 30 min and analyzed for triacylglycerol (TAG), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, oxidized low-density lipoprotein cholesterol, myeloperoxidase, paraoxonase-1 activity, and insulin. RESULTS: The TAG incremental area under the curve (iAUC) during the three meal condition (321 ± 129 mg/dl · 12 h) was significantly lower (P = 0.04) compared with the six meal condition (481 ± 155 mg/dl · 12 h). The insulin iAUC during the three meal condition (5,549 ± 1,007 pmol/l · 12 h) was significantly higher (P = 0.05) compared with the six meal condition (4,230 ± 757 pmol/l(.) 12 h). Meal frequency had no influence on the other biochemical variables. CONCLUSIONS: Collectively, a three and six isocaloric high-carbohydrate meal frequency pattern differentially alters postprandial TAG and insulin concentrations but has no effect on postprandial cholesterol, oxidative stress, or antioxidant activity in obese women.

Liquid meal composition, postprandial satiety hormones, and perceived appetite and satiety in obese women during acute caloric restriction.

OBJECTIVE: The purpose of this study was to compare postprandial satiety regulating hormone responses (pancreatic polypeptide (PP) and peptide tyrosine tyrosine (PYY)) and visual analog scale- (VAS) assessed perceived appetite and satiety between liquid high-protein (HP) and high-carbohydrate (HC) meals in obese women during acute (24-h) caloric restriction. DESIGN: Eleven obese premenopausal women completed two conditions in random order in which they consumed 1500 calories as six 250-calorie HP meals or six 250-calorie HC meals over a 12-h period. Blood samples were taken at baseline and every 20 min thereafter and analyzed for PP and PYY concentrations. At these same points, perceived hunger and fullness were assessed with a VAS. The incremental area under the curve (iAUC) was used to compare postprandial responses. RESULTS: The 12-h PP and PYY iAUC were greater (P≤0.05) during the HP condition (PP: 4727±1306 pg/ml×12 h, PYY: 1373±357 pg/ml×12 h) compared with the HC condition (PP: 2300±528 pg/ml×12 h, PYY: 754±246 pg/ml×12 h). Perceived hunger and fullness were not different between conditions (P>0.05). The greatest changes in PYY and perceived fullness occurred after the morning meals during both conditions. CONCLUSIONS: These data suggest that in obese women during acute caloric restriction before weight loss, i) liquid HP meals, compared with HC meals, result in greater postprandial PP and PYY concentrations, an effect not associated with differential appetite or satiety responses, and ii) meal-induced changes in PYY and satiety are greatest during the morning period, regardless of dietary macronutrient composition.

Early versus delayed percutaneous coronary intervention for patients with non-ST segment elevation acute coronary syndrome: a meta-analysis of randomized controlled clinical trials.

BACKGROUND: Studies assessing the timing of percutaneous coronary interventions (PCI) in patients with Non-ST segment elevation Acute Coronary Syndromes (NSTE-ACS) have failed to generate a consensus on how early PCI should be performed in such patients. PURPOSE: This meta-analysis compares clinical outcomes at 30 days in NSTE-ACS patients undergoing PCI within 24 hours of presentation (early PCI) with those receiving PCI more than 24 hours after presentation (delayed PCI). DATA SOURCES: Data were extracted from searches of MEDLINE (1990-2010) and Google scholar and from scrutiny of abstract booklets from major cardiology meetings (1990-2010). STUDY SELECTION: Randomized clinical trials (RCTs) that included the composite endpoint of death and non-fatal myocardial infarction (MI) at 30 days after PCI were considered. DATA EXTRACTION: Two independent reviewers extracted data using standard forms. The effects of early and delayed PCI were analyzed by calculating pooled estimates for death, non-fatal MI, bleeding, repeat revascularization and the composite endpoint of death or non-fatal MI at 30 days. Univariate analysis of each of these variables was used to create odds ratios. DATA SYNTHESIS: Seven studies with a total of 13,762 patients met the inclusion criteria. There was no significant difference in the odds of the composite endpoint of death or non-fatal MI at 30 days between patients undergoing early PCI and those receiving delayed PCI (OR-0.83, 95%CI 0.62-1.10). Patients receiving delayed PCI experienced a 33% reduction in the odds of repeat revascularization at 30 days compared to those undergoing early PCI (OR-1.33, 95%CI 1.14-1.56, P=0.0004).Conversely, patients undergoing early PCI experienced lower odds of bleeding than those receiving delayed PCI (OR-0.76, 95%CI 0.63-0.91, P = 0.0003). CONCLUSIONS: In NSTE-ACS patients early PCI doesn't reduce the odds of the composite endpoint of death or non-fatal MI at 30 day. This strategy is associated with lower odds of bleeding and higher odds of repeat revascularization at 30 days than a strategy of delayed PCI.

Heart failure with preserved ejection fraction: chronic low-intensity interval exercise training preserves myocardial O2 balance and diastolic function.

We have previously reported chronic low-intensity interval exercise training attenuates fibrosis, impaired cardiac mitochondrial function, and coronary vascular dysfunction in miniature swine with left ventricular (LV) hypertrophy (Emter CA, Baines CP. Am J Physiol Heart Circ Physiol 299: H1348-H1356, 2010; Emter CA, et al. Am J Physiol Heart Circ Physiol 301: H1687-H1694, 2011). The purpose of this study was to test two hypotheses: 1) chronic low-intensity interval training preserves normal myocardial oxygen supply/demand balance; and 2) training-dependent attenuation of LV fibrotic remodeling improves diastolic function in aortic-banded sedentary, exercise-trained (HF-TR), and control sedentary male Yucatan miniature swine displaying symptoms of heart failure with preserved ejection fraction. Pressure-volume loops, coronary blood flow, and two-dimensional speckle tracking ultrasound were utilized in vivo under conditions of increasing peripheral mean arterial pressure and ß-adrenergic stimulation 6 mo postsurgery to evaluate cardiac function. Normal diastolic function in HF-TR animals was characterized by prevention of increased time constant of isovolumic relaxation, normal LV untwisting rate, and enhanced apical circumferential and radial strain rate. Reduced fibrosis, normal matrix metalloproteinase-2 and tissue inhibitors of metalloproteinase-4 mRNA expression, and increased collagen III isoform mRNA levels (P < 0.05) accompanied improved diastolic function following chronic training. Exercise-dependent improvements in coronary blood flow for a given myocardial oxygen consumption (P < 0.05) and cardiac efficiency (stroke work to myocardial oxygen consumption, P < 0.05) were associated with preserved contractile reserve. LV hypertrophy in HF-TR animals was associated with increased activation of Akt and preservation of activated JNK/SAPK. In conclusion, chronic low-intensity interval exercise training attenuates diastolic impairment by promoting compliant extracellular matrix fibrotic components and preserving extracellular matrix regulatory mechanisms, preserves myocardial oxygen balance, and promotes a physiological molecular hypertrophic signaling phenotype in a large animal model resembling heart failure with preserved ejection fraction.

A new twist on an old idea: a two-dimensional speckle tracking assessment of cyclosporine as a therapeutic alternative for heart failure with preserved ejection fraction.

We recently reported that mitochondrial dysfunction, characterized by increased mitochondrial permeability transition (MPT), was present in a translational swine model of heart failure with preserved ejection fraction (HFpEF). Cyclophilin D is a key component of the MPT pore, therefore, the purpose of this study was to test the efficacy of a novel cyclosporine (CsA) dosing scheme as a therapeutic alternative for HFpEF. Computed tomography (CT), two-dimensional speckle tracking two-dimensional speckle tracking (2DST), and invasive hemodynamics were used to evaluate cardiac function. CT imaging showed 14 weeks of CsA treatment caused eccentric myocardial remodeling (contrasting concentric remodeling in untreated HF animals) and elevated systemic pressures. 2DST detected left ventricular (LV) mechanics associated with systolic and diastolic dysfunction prior to the onset of significantly increased LV end diastolic pressure including: (1) decreased systolic apical rotation rate, longitudinal displacement, and longitudinal/radial/circumferential strain; (2) decreased early diastolic untwisting and longitudinal strain rate; and (3) increased late diastolic radial/circumferential mitral strain rate. LV mechanics associated with systolic and diastolic impairment was enhanced to a greater extent than seen in untreated HF animals following CsA treatment. In conclusion, CsA treatment accelerated the development of heart failure, including dilatory LV remodeling and impaired systolic and diastolic mechanics. Although our findings do not support CsA as a viable therapy for HFpEF, 2DST was effective in differentiating between progressive gradations of developing HF and detecting diastolic impairment prior to the development of overt diastolic dysfunction.

Dyslipidemia in patients with chronic and end-stage kidney disease.

In this review, we discuss the physiology, diagnosis and treatment of dyslipidemia in patients with chronic and end-stage renal disease. The recent important clinical trials in patients with chronic kidney disease and dyslipidemia are reviewed. Because of the lack of evidence in treating lipid abnormalities in this specific patient population, we propose that future studies should focus on the pathophysiological mechanisms and treatment of dyslipidemia in this special patient population.