Improving Practice Guideline Adherence Through Peer Feedback: Impact of an Ambulatory Cardiology Curriculum.

PROBLEM: Graduate medical trainees must be prepared to practice in a quality-driven system that values adherence to and documentation of evidence-based care. Few validated approaches exist to teach these skills. Our objective was to develop, implement, and evaluate an ambulatory practice improvement curriculum capitalizing on peer feedback aimed at improving cardiology fellow guideline knowledge, adherence, and chart documentation. INTERVENTION: Four outpatient topics were reviewed in dedicated 1-hour sessions: stable ischemic heart disease, heart failure, atrial fibrillation, and aortic valvular disease. Each session began with peer review, critique, and guideline adherence discussion of deidentified outpatient fellow clinic charts, followed by discussion of clinical guidelines. The open discussion of real clinic notes provided a forum for peer feedback exchange. Before each session and after the final session, participants completed a multiple-choice knowledge assessment and self-assessment of comfort with the guidelines. To evaluate the potential effect on patient care, random clinic chart audits were conducted before and after the curriculum using a chart scoring system. CONTEXT: Although the format is broadly applicable, the specific curriculum content was designed for a cardiology fellowship cohort in a large academic medical center. It was organized and implemented by 2 cardiology fellows under the direction and supervision of program directors. The curriculum was implemented during prescheduled noon conference hours. The intention was to carry forward this ambulatory curriculum in subsequent years and to use the first 4 sessions to study its potential successes and opportunities for improvement. OUTCOME: All 22 general cardiology fellows attended at least two sessions (M = 3.1). Knowledge test scores rose from 52.6% to 73.0% (20.4% increase, p < .001), 95% confidence interval (CI) [13.6%, 27.2%]. Self-reported guidelines knowledge improved by 15.1% (p = .002), 95% CI [6.2%, 24.0%], and self-reported documentation improved by 12.5% (p = .008), 95% CI [3.8%, 21.7%]. Chart audit scores improved by 17.8% (p < .001), 95% CI [10.6%, 25.0%], driven in part by 16.4% improvement in adherence to Class I therapies (p = .001). LESSONS LEARNED: A targeted curriculum combining peer chart review, feedback, and guideline discussion was associated with significant improvement in fellows' knowledge and adherence to evidence-based therapies. Peer assessment and group-based education and feedback can be leveraged to improve trainee education and impact patient care.

Cardiac implanted electronic device-related infective endocarditis: clinical features, management, and outcomes of 80 consecutive patients.

BACKGROUND: The use of cardiac implantable electronic devices (CIEDs) has expanded dramatically over the past decade, but net clinical benefit has been curtailed by increasing infectious complications. In particular, CIED-related infectious endocarditis (IE) is a serious condition with significant morbidity and mortality. METHODS: We performed a single-center, retrospective study between July 2006 and February 2011 with CIED-related IE, defined by either lead vegetations detected on echocardiography or by fulfilling Duke criteria for definite endocarditis. Clinical parameters and outcomes were detailed by electronic medical record review and vital status was confirmed by the Social Security Death Index. RESULTS: Eighty patients (median age 67, interquartile range 56-75, 58 M/22 F) were diagnosed with CIED-related IE. Overall mortality was 36% with a median time to death of 95 days from presentation. Over half (52%) of the deaths were infection related with a median time to death of 29 days. Multivariate analysis showed methicillin-resistant Staphylococcus aureus (MRSA) infection (odds ratio [OR] 0.158; 95% confidence interval [CI], 0.047-0.534; P = .003) and concomitant valve endocarditis (OR 0.141, CI 0.041-0.491, P = .002) independently predicted mortality. CONCLUSION: In this contemporary series, all-cause mortality in patients with CIED-related IE was high with a short time to death from onset of infection. MRSA and concomitant valve infection were the most powerful independent predictors of mortality.

Safety of sapropterin dihydrochloride (6r-bh4) in patients with pulmonary hypertension.

The authors investigated the safety of oral tetrahydrobiopterin (BH4), a cofactor for nitric oxide synthesis, as a novel treatment for pulmonary hypertension (PH). Eighteen patients with pulmonary arterial hypertension or inoperable chronic thromboembolic PH received sapropterin dihydrochloride (6R-BH4), the optically active form of BH4, in addition to treatment with sildenafil and/or endothelin receptor antagonists in an open-label, dose-escalation study. 6R-BH4 was administered starting at a dose of 2.5 mg/kg and increasing to 20 mg/kg over 8 weeks. Changes in markers of nitric oxide synthesis, inflammation and oxidant stress, as well as exercise capacity and cardiac function were measured. 6R-BH4 was well tolerated at all doses without systemic hypotension, even when given in combination with sildenafil. There was a small but significant reduction in plasma monocyte chemoattractant protein (MCP)-1 levels on 5 mg/kg. No significant changes in measures of nitric oxide synthesis or oxidant stress were observed. There was improvement in 6-minute walk distance, most significant at a dose of 5 mg/kg, from 379 ± 61 to 413 ± 57 m 414 ± 57 m (P = .002). Oral 6R-BH4 can be administered safely in doses up to 20 mg/kg daily to patients with PH. Further studies are needed to explore its therapeutic potential.

Aortic root spontaneous echocardiographic contrast due to haemodynamic support with a percutaneous left ventricular assist device (TandemHeart).

Intra-procedural transoesophageal echocardiography (TEE) is useful in guiding device placement and monitoring for procedural complications in the interventional lab. We report a case of spontaneous echo contrast (SEC) formation in the aortic root immediately following initiation of haemodynamic support with a percutaneous left ventricular (LV) assist device for cardiogenic shock. With TEE guidance, assist device flow rates were adjusted, resulting in resolution of SEC. This case illustrates another potential use for intra-procedural TEE during LV assist device placement.

Lower cardiac output is associated with neurodegeneration among older adults with normal cognition but not mild cognitive impairment.

Subclinical cardiac dysfunction is associated with smaller total brain volume on magnetic resonance imaging (MRI). To study whether cardiac output relates to regional measurements of grey and white matter structure, older adults (n = 326) underwent echocardiogram to quantify cardiac output (L/min) and brain MRI. Linear regressions related cardiac output to grey matter volumes measured on T1 and white matter hyperintensities assessed on T2-FLAIR. Voxelwise analyses related cardiac output to diffusion tensor imaging adjusting for demographic, genetic, and vascular risk factors. Follow-up models assessed a cardiac output x diagnosis interaction with stratification (normal cognition, mild cognitive impairment). Cardiac output interacted with diagnosis, such that lower cardiac output related to smaller total grey matter (p = 0.01), frontal lobe (p = 0.01), and occipital lobe volumes (p = 0.01) among participants with normal cognition. When excluding participants with cardiovascular disease and atrial fibrillation, associations emerged with smaller parietal lobe (p = 0.005) and hippocampal volume (p = 0.05). Subtle age-related cardiac changes may disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.

Lower Cardiac Output Relates to Longitudinal Cognitive Decline in Aging Adults.

BACKGROUND: Subclinical reductions in cardiac output correspond to lower cerebral blood flow (CBF), placing the brain at risk for functional changes. OBJECTIVES: This study aims to establish the consequences of reduced cardiac output on longitudinal cognitive outcomes in aging adults. METHODS: Vanderbilt Memory and Aging Project participants free of clinical dementia and heart failure (n = 306, 73 ± 7, 58% male) underwent baseline echocardiography to assess cardiac output (L/min) and longitudinal neuropsychological assessment at baseline, 18 months, 3 and 5 years. Linear mixed-effects regressions related cardiac output to trajectory for each longitudinal neuropsychological outcome, adjusting for age, sex, race/ethnicity, education, body surface area, Framingham Stroke Risk Profile score, apolipoprotein E (APOE) ε4 status and follow-up time. Models were repeated, testing interactions with cognitive diagnosis and APOE-ε4 status. RESULTS: Lower baseline cardiac output related to faster declines in language (ß = 0.11, p = 0.01), information processing speed (ß = 0.31, p = 0.006), visuospatial skills (ß = 0.09, p = 0.03), and episodic memory (ß = 0.02, p = 0.001). No cardiac output x cognitive diagnosis interactions were observed (p > 0.26). APOE-ε4 status modified the association between cardiac output and longitudinal episodic memory (ß = 0.03, p = 0.047) and information processing speed outcomes (ß = 0.55, p = 0.02) with associations stronger in APOE-ε4 carriers. CONCLUSION: The present study provides evidence that even subtle reductions in cardiac output may be associated with more adverse longitudinal cognitive health, including worse language, information processing speed, visuospatial skills, and episodic memory performances. Preservation of healthy cardiac functioning is important for maintaining optimal brain aging among older adults.

Lower Left Ventricular Ejection Fraction Relates to Cerebrospinal Fluid Biomarker Evidence of Neurodegeneration in Older Adults.

BACKGROUND: Subclinical cardiac dysfunction is associated with decreased cerebral blood flow, placing the aging brain at risk for Alzheimer's disease (AD) pathology and neurodegeneration. OBJECTIVE: This study investigates the association between subclinical cardiac dysfunction, measured by left ventricular ejection fraction (LVEF), and cerebrospinal fluid (CSF) biomarkers of AD and neurodegeneration. METHODS: Vanderbilt Memory & Aging Project participants free of dementia, stroke, and heart failure (n = 152, 72±6 years, 68% male) underwent echocardiogram to quantify LVEF and lumbar puncture to measure CSF levels of amyloid-ß42 (Aß42), phosphorylated tau (p-tau), and total tau (t-tau). Linear regressions related LVEF to CSF biomarkers, adjusting for age, sex, race/ethnicity, education, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E ɛ4 status. Secondary models tested an LVEF x cognitive diagnosis interaction and then stratified by diagnosis (normal cognition (NC), mild cognitive impairment (MCI)). RESULTS: Higher LVEF related to decreased CSF Aß42 levels (ß= -6.50, p = 0.04) reflecting greater cerebral amyloid accumulation, but this counterintuitive result was attenuated after excluding participants with cardiovascular disease and atrial fibrillation (p = 0.07). We observed an interaction between LVEF and cognitive diagnosis on CSF t-tau (p = 0.004) and p-tau levels (p = 0.002), whereas lower LVEF was associated with increased CSF t-tau (ß= -9.74, p = 0.01) and p-tau in the NC (ß= -1.41, p = 0.003) but not MCI participants (p-values>0.13). CONCLUSIONS: Among cognitively normal older adults, subclinically lower LVEF relates to greater molecular evidence of tau phosphorylation and neurodegeneration. Modest age-related changes in cardiovascular function may have implications for pathophysiological changes in the brain later in life.

Apolipoprotein E Genotype Modifies the Association Between Cardiac Output and Cognition in Older Adults.

Background Subtle reductions in cardiac output relate to lower cerebral blood flow, especially in regions where Alzheimer's disease pathology first develops. Apolipoprotein E (APOE)-ε4 is a genetic susceptibility risk factor for Alzheimer's disease that also moderates vascular damage. This study investigated whether APOE-ε4 carrier status modifies the cross-sectional association between cardiac output and cognition. Methods and Results Vanderbilt Memory & Aging Project participants free of clinical stroke and dementia (n=306, 73±7 years, 42% female) underwent echocardiography to determine cardiac output (L/min), comprehensive neuropsychological assessment, and venous blood draw to determine APOE genotype and ε4 carrier status. Linear regressions related cardiac output to neuropsychological test performance, adjusting for age, sex, education, race/ethnicity, body surface area, cognitive diagnosis, Framingham Stroke Risk Profile, and APOE-ε4 status. Main effect models were null (P>0.19). With identical covariates, models were repeated testing a cardiac output×APOE-ε4 status interaction and again stratified by ε4 carrier status. Cardiac output×APOE-ε4 status related to naming (ß=0.91, P=0.0009), category fluency (ß=1.2, P=0.01), information processing speed (ß=-5.4, P=0.001), visuospatial skill (ß=0.85, P=0.003), and executive function performances (ß=0.22, P=0.002). Stratified models suggested that lower cardiac output was associated with worse neuropsychological performances among APOE-ε4 carriers. Conclusions APOE-ε4 carrier status appears to modify the cross-sectional association between cardiac output and neuropsychological performance such that lower cardiac output relates to poorer performances among carriers of the ε4 allele. These findings add to increasing evidence that APOE-ε4 carrier status has important implications for associations between vascular and brain health in aging adults.

Calmodulin kinase II inhibition disrupts cardiomyopathic effects of enhanced green fluorescent protein.

Transgenic expression of enhanced green fluorescent protein (eGFP) in myocardium can result in cardiac dysfunction and cardiomyopathy, presumably through toxic effects that disrupt normal cellular signaling. The multifunctional Ca(2+)- and calmodulin-dependent protein kinase II (CaMKII) is widely expressed in myocardium and CaMKII activity is increased in human and animal models of cardiomyopathy, so we hypothesized that increased CaMKII activity is important for cardiomyopathy due to transgenic expression of eGFP. Here we report that cardiomyocyte-delimited eGFP over-expression causes increased CaMKII activity that predicts left ventricular dilation and dysfunction. On the other hand, transgenic co-expression of a CaMKII inhibitory peptide with eGFP prevents eGFP-mediated left ventricular dilation and dysfunction. These findings suggest that increased CaMKII activity is a critical pathological signal in transgenic cardiomyopathy due to eGFP over-expression.

Effects of Advanced Cardiac Procedure Simulator Training on Learning and Performance in Cardiovascular Medicine Fellows.

BACKGROUND: Simulation-based training has been used in medical training environments to facilitate the learning of surgical and minimally invasive techniques. We hypothesized that integration of a procedural simulation curriculum into a cardiology fellowship program may be educationally beneficial. METHODS: We conducted an 18-month prospective study of cardiology trainees at Vanderbilt University Medical Center. Two consecutive classes of first-year fellows (n = 17) underwent a teaching protocol facilitated by simulated cases and equipment. We performed knowledge and skills evaluations for 3 procedures (transvenous pacing [TVP] wire, intra-aortic balloon pump [IABP], and pericardiocentesis [PC]). The index class of fellows was reevaluated at 18 months postintervention to measure retention. Using nonparametric statistical tests, we compared assessments of the intervention group, at the time of intervention and 18 months, with those of third-year fellows (n = 7) who did not receive simulator-based training. RESULTS: Compared with controls, the intervention cohort had higher scores on the postsimulator written assessment, TVP skills assessment, and IABP skills assessment (P = .04, .007, and .02, respectively). However, there was no statistically significant difference in scores on the PC skills assessment between intervention and control groups (P = .08). Skills assessment scores for the intervention group remained higher than the controls at 18 months (P = .01, .004, and .002 for TVP, IABP, and PC, respectively). Participation rate was 100% (24/24). CONCLUSIONS: Procedural simulation training may be an effective tool to enhance the acquisition of knowledge and technical skills for cardiology trainees. Future studies may address methods to improve performance retention over time.

Death, cardiac dysfunction, and arrhythmias are increased by calmodulin kinase II in calcineurin cardiomyopathy.

BACKGROUND: Activation of cellular Ca2+ signaling molecules appears to be a fundamental step in the progression of cardiomyopathy and arrhythmias. Myocardial overexpression of the constitutively active Ca2+-dependent phosphatase calcineurin (CAN) causes severe cardiomyopathy marked by left ventricular (LV) dysfunction, arrhythmias, and increased mortality rate, but CAN antagonist drugs primarily reduce hypertrophy without improving LV function or risk of death. METHODS AND RESULTS: We found that activity and expression of a second Ca2+-activated signaling molecule, calmodulin kinase II (CaMKII), were increased in hearts from CAN transgenic mice and that CaMKII-inhibitory drugs improved LV function and suppressed arrhythmias. We devised a genetic approach to "clamp" CaMKII activity in CAN mice to control levels by interbreeding CAN transgenic mice with mice expressing a specific CaMKII inhibitor in cardiomyocytes. We developed transgenic control mice by interbreeding CAN transgenic mice with mice expressing an inactive version of the CaMKII-inhibitory peptide. CAN mice with CaMKII inhibition had reduced risk of death and increased LV and ventricular myocyte function and were less susceptible to arrhythmias. CaMKII inhibition did not reduce transgenic overexpression of CAN or expression of endogenous CaMKII protein or significantly reduce most measures of cardiac hypertrophy. CONCLUSIONS: CaMKII is a downstream signal in CAN cardiomyopathy, and increased CaMKII activity contributes to cardiac dysfunction, arrhythmia susceptibility, and longevity during CAN overexpression.

Restrictive Cardiomyopathy Associated With Long-Term Use of Hydroxychloroquine for Systemic Lupus Erythematosus.

Hydroxychloroquine (HQ) is commonly prescribed for autoimmune diseases such as systemic lupus erythematosus. We report a case of a 75-year-old female presenting with de novo decompensated heart failure and restrictive cardiomyopathy (left ventricular ejection fraction: 40%-45%) after treatment with HQ for more than 11 years. Hydroxychloroquine was discontinued, and follow-up echocardiogram 57 days after discontinuation showed normalization of her left ventricular ejection fraction. A score of 7 on the Naranjo Adverse Drug Reaction Probability Scale indicates that HQ is a probable cause of this patient's cardiomyopathy. An adverse drug effect due to HQ should be considered in treated patients who present with restrictive cardiomyopathy. Discontinuation may allow for partial or complete reversal of the cardiomyopathy.

Lower cardiac index levels relate to lower cerebral blood flow in older adults.

OBJECTIVE: To assess cross-sectionally whether lower cardiac index relates to lower resting cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) among older adults. METHODS: Vanderbilt Memory & Aging Project participants free of stroke, dementia, and heart failure were studied (n = 314, age 73 ± 7 years, 59% male, 39% with mild cognitive impairment). Cardiac index (liters per minute per meter squared) was quantified from echocardiography. Resting CBF (milliliters per 100 grams per minute) and hypercapnia-induced CVR were quantified from pseudo-continuous arterial spin-labeling MRI. Linear regressions with ordinary least-square estimates related cardiac index to regional CBF, with adjustment for age, education, race/ethnicity, Framingham Stroke Risk Profile score (systolic blood pressure, antihypertensive medication use, diabetes mellitus, current cigarette smoking, left ventricular hypertrophy, prevalent cardiovascular disease [CVD], atrial fibrillation), APOE ε4 status, cognitive diagnosis, and regional tissue volume. RESULTS: Lower cardiac index corresponded to lower resting CBF in the left (ß = 2.4, p = 0.001) and right (ß = 2.5, p = 0.001) temporal lobes. Results were similar when participants with prevalent CVD and atrial fibrillation were excluded (left temporal lobe ß = 2.3, p = 0.003; right temporal lobe ß = 2.5, p = 0.003). Cardiac index was unrelated to CBF in other regions assessed (p > 0.25) and CVR in all regions (p > 0.05). In secondary cardiac index × cognitive diagnosis interaction models, cardiac index and CBF associations were present only in cognitively normal participants and affected a majority of regions assessed with effects strongest in the left (p < 0.0001) and right (p < 0.0001) temporal lobes. CONCLUSIONS: Among older adults without stroke, dementia, or heart failure, systemic blood flow correlates with cerebral CBF in the temporal lobe, independently of prevalent CVD, but not CVR.

Faculty Development on Clinical Teaching Skills: An Effective Model for the Busy Clinician.

INTRODUCTION: The authors developed and evaluated a faculty development program on clinical teaching skills to address barriers to participation and to impact teaching behaviors. METHODS: Four one-hour workshops were implemented over five months. Evaluation included participant satisfaction and pre/post self-assessment. Pre/post faculty teaching ratings by trainees were compared. RESULTS: A total of 82% of faculty (N = 41) attended. Participants rated workshops highly (mean, 4.43/5.00). Self-assessment of skills and comfort with teaching activities improved. A total of 59% of residents and 40% of fellows felt that teaching received from participating faculty was highly effective. The majority observed targeted teaching behaviors by the faculty. Teaching ratings improved after the workshops (P = 0.042). CONCLUSION: Our series of short workshops during a standing conference time was associated with increased self-assessed skill and comfort and an increase in faculty ratings on teaching evaluations. Effective faculty development programs can be implemented in flexible formats and overcome common barriers to participation.

A Phase I, Single Ascending Dose Study of Cimaglermin Alfa (Neuregulin 1ß3) in Patients With Systolic Dysfunction and Heart Failure.

A first-in-human, phase 1, double blind, placebo-controlled, single ascending dose study examined the safety, tolerability, and exploratory efficacy of intravenous infusion of a recombinant growth factor, cimaglermin alfa, in patients with heart failure and left ventricular systolic dysfunction (LVSD). In these patients on optimal guideline-directed medical therapy, cimaglermin treatment was generally tolerated except for transient nausea and headache and a dose-limiting toxicity was noted at the highest planned dose. There was a dose-dependent improvement in left ventricular ejection fraction lasting 90 days following infusion. Thus, cimaglermin is a potential therapy to enhance cardiac function in LVSD and warrants further investigation.