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James A. Arrighi, MD, FACC, Chair Lisa A. Mendes, MD, FACC, Co-Chair Jesse E. Adams iii, MD, FACC[∗][1] John E. Brush, Jr, MD, FACC[∗][1] G. William Dec, Jr, MD, FACC Ali Denktas, MD, FACC Susan M. Fernandes, LPD, PA-C Sanjeev A. Francis, MD, FACC Rosario Freeman, MD, MS, FACC[∗][1

Introduction: Right ventricular failure (RVF) remains a major cause of morbidity and mortality after continuous flow Left Ventricle Assist Device (CF-LVAD) implantation. Previous risk assessments using pre-operative data to predict RVF have performed only modestly well. Methods: We retrospectively studied the potential of echocardiographic RV dP/dt - a non-invasive measure of right ventricular contractility derived from the Doppler signal of tricuspid regurgitation, to predict post-LVAD RVF in patients who were inotrope-independent and those who were on inotropic therapy prior to LVAD. Sixty-five consecutive CF-LVAD recipients at Vanderbilt University Medical Center from 2013-2019 who had a baseline echocardiogram without inotrope support within 3 months prior to LVAD implantation were included. Forty patients from the cohort were started on inotropes prior to LVAD implantation. Baseline off-inotrope and on-inotrope RV dP/dt data were analyzed. Severity of post-LVAD RVF was defined by INTERMACS criteria. Results: Of the 65 studied patients, 30 patients had none or mild RVF, 17 had moderate RVF, and 18 had severe RVF. Patients with severe RVF had markedly poorer survival outcome than no/mild and moderate RVF patients. Baseline RV dP/dt was significantly lower in patients who developed post-LVAD severe RVF. A baseline off-inotrope, or on-inotrope RV dP/dt ≥ 300 mmHg/s predicted a low risk of severe RVF with high sensitivity (89% and 80%, respectively) and negative predictive value (91% and 88% respectively); while the presence of both off-inotrope and on-inotrope RV dP/dt < 300 mmHg/s was associated with a high likelihood of post-LVAD RVF (OR 10.5, 95% 1.8-59.4 compared to the rest of the cohort on inotrope therapy). Conclusion: Echocardiographic RV dP/dt may be a valuable adjunct tool for prediction of post-LVAD severe RVF in patients undergoing evaluation for LVAD implantation.

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 T(1) and white matter hyperintensities assessed on T(2)-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 contribute to disrupt neuronal homeostasis and impact grey matter integrity prior to cognitive impairment.

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair Jesse E. Adams III, MD, FACC James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC[†][1] Eric R. Bates, MD, FACC[†][1] John E. Brush, Jr, MD, FACC Lori Daniels, MD, MAS, FACC[†][1] Ali Denktas, MD, FACC Susan

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 (β = 2.4, p = 0.001) and right (β = 2.5, p = 0.001) temporal lobes. Results were similar when participants with prevalent CVD and atrial fibrillation were excluded (left temporal lobe β = 2.3, p = 0.003; right temporal lobe β = 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.

[Figure][1] Approximately 6.5 million Americans experience heart failure (HF), which contributes to 1 in 8 deaths each year [(1)][2]. Current therapies improve survival for HF with reduced ejection fraction, but a result has been to increase the number of HF patients who progress to

Visual Abstract, Highlights • Cimaglermin is a recombinant neuregulin that appears to be important for essential cardiac repair processes. • Forty patients with significant left ventricular dysfunction and heart failure were randomized in a phase 1 double blind, placebo controlled, single ascending dose study to examine safety and tolerability. • An infusion of cimaglermin was generally tolerated except for transient nausea and headache. • A dose-limiting toxicity of transient elevated liver transaminases and bilirubin was observed at the highest planned dose. • There was a sustained improvement in left ventricular ejection fraction over 3 months at higher doses tested compared to lower doses or placebo., Summary 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.

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 (β=0.91, P =0.0009), category fluency (β=1.2, P =0.01), information processing speed (β=−5.4, P =0.001), visuospatial skill (β=0.85, P =0.003), and executive function performances (β=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.

Introduction: Multi-modality imaging is a crucial component of cardiovascular (CV) fellowship training and requires knowledge of CV anatomy for interpretation. We hypothesized that hands-on anatomy education would improve the imaging interpretation skills of CV fellows. Methods: The first-year CV fellowship class completed a hands-on cadaveric anatomy session correlated with clinical imaging. Fellows’ ability to identify CV structures on cardiac imaging was assessed using a 30-question assessment tool administered at baseline and 1 week and 6 months post intervention. Advanced CV fellows (second or third year) who had not attended the session were also tested. Scores were expressed as median [interquartile range]. Results: Among 9 first-year fellows, the majority reported no formal anatomy training since medical school (N = 7) and rated their knowledge of CV anatomy as fair or poor (N = 7) prior to the intervention. The median assessment score was higher 1 week after intervention vs baseline (24 [23-25] vs 19 [17-21]; P = .013) and remained higher than baseline at 6 months (26 [26-28] vs 19 [17-21]; P = .009). The 6-month post-intervention score for first-year fellows was not significantly different than that of senior fellows (n = 10) not exposed to the intervention (26 [26-28] vs 26 [23-27]; P = .434). Conclusions: Gross anatomy instruction improved first-year CV fellows’ interpretation of CV imaging. Anatomic instruction may be a useful adjunct to multi-modality imaging education.

There has been rapid advancement within the field of cardiovascular disease (CVD) with increasing disease complexity and rapidly evolving technologies. These changes present new challenges in training the next generation of cardiologists. In parallel, there has been an evolution in graduate medical

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC John E. Brush, Jr, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, MAS, FACC Susan Fernandes, LPD, PA-C Rosario Freeman, MD, MS, FACC

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC John E. Brush, Jr, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, MAS, FACC Akshay Desai, MD, FACC[‡][1] Douglas E. Drachman, MD

Right Ventricular failure (RVF) contributes significantly to early mortality after Left Ventricular Assisting Device (LVAD) implantation. At present, there is no good predictor of post-LVAD RV function. Echocardiographic (echo) RV dP/dt is a non-invasive parameter measuring the rate of rise in the

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.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.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.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).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.

Eosinophilic myocarditis is a rare condition in which inflammation of the heart results in an infiltrative cardiomyopathy that is often difficult to diagnose in the acute setting. It sometimes presents as left ventricular hypertrophy. The authors present a case of a 79-year-old woman with a history of Non-Hodgkin's lymphoma who presented with acute heart failure with marked left ventricular hypertrophy. Echocardiography demonstrated abnormalities consistent with an infiltrative cardiomyopathy, and endomyocardial biopsy showed findings consistent with eosinophilic myocarditis. The patient was managed with diuresis and glucocorticoid therapy, and within 4 weeks of her admission, her clinical status had improved and her echocardiogram normalized. The prompt diagnosis and treatment of this patient's myocarditis likely resulted in her favorable outcome. This illustrates the need for a broad consideration of all the potential causes of hypertrophy and the necessary diagnostic strategies and therapeutic options.

Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS),1 the American College of Cardiology (ACC) has played a central role in defining the knowledge, experiences, skills, and behaviors expected of all clinical cardiologists upon completion of training. Subsequent updates have incorporated major advances and revisions—both in content and structure—including, most recently, …

With Accreditation Council for Graduate Medical Education core competencies [(1)][1], there was a shift from time- to competency-based training. Milestones for internal medicine (IM) residents and cardiovascular medicine (CVM) fellows have created an opportunity to rethink progression through

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.

Eric S. Williams, MD, MACC, Chair Jonathan L. Halperin, MD, FACC, Co-Chair James A. Arrighi, MD, FACC Eric H. Awtry, MD, FACC Eric R. Bates, MD, FACC Salvatore Costa, MD, FACC Lori Daniels, MD, FACC Akshay Desai, MD, FACC Douglas E. Drachman, MD, FACC Susan Fernandes, LPD, PA-C Rosario

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.

Vascular health factors frequently co-occur with Alzheimer's disease (AD). A better understanding of how systemic vascular and cerebrovascular health intersects with clinical and pathological AD may inform prevention and treatment opportunities.To establish the Vanderbilt Memory & Aging Project, a case-control longitudinal study investigating vascular health and brain aging, and describe baseline methodology and participant characteristics.From September 2012 to November 2014, 335 participants age 60- 92 were enrolled, including 168 individuals with mild cognitive impairment (MCI, 73±8 years, 41% female) and 167 age-, sex-, and race-matched cognitively normal controls (NC, 72±7 years, 41% female). At baseline, participants completed a physical and frailty examination, fasting blood draw, neuropsychological assessment, echocardiogram, cardiac MRI, and brain MRI. A subset underwent 24-hour ambulatory blood pressure monitoring and lumbar puncture for cerebrospinal fluid (CSF) collection.As designed, participant groups were comparable for age (p = 0.31), sex (p = 0.95), and race (p = 0.65). MCI participants had greater Framingham Stroke Risk Profile scores (p = 0.008), systolic blood pressure values (p = 0.008), and history of left ventricular hypertrophy (p = 0.04) than NC participants. As expected, MCI participants performed worse on all neuropsychological measures (p-values < 0.001), were more likely to be APOEɛ4 carriers (p = 0.02), and had enhanced CSF biomarkers, including lower Aβ42 (p = 0.02), higher total tau (p = 0.004), and higher p-tau (p = 0.02) compared to NC participants.Diverse sources of baseline and longitudinal data will provide rich opportunities to investigate pathways linking vascular and cerebrovascular health, clinical and pathological AD, and neurodegeneration contributing to novel strategies to delay or prevent cognitive decline.

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.

Introduction Right ventricle failure (RVF) remains a major source of morbidity and mortality with Left Ventricle Assist devices (LVAD) use. Common invasive and non-invasive measurements of RV function have not been predictive of RVF post-LVAD placement. The rate of rise of intra-ventricular pressure (dP/dt) correlates with myocardial contractility and is less dependent of loading conditions. We sought to evaluate if TTE derived dP/dt predicts early RVF after LVAD implantation. Methods We retrospectively reviewed all patients who had TTE, off inotropic support within 3 months prior to LVAD implant in our center. RV dP/dt was assessed by two independent reviewers using continuous-wave TR Doppler recordings. The time required for TR velocity to increase from 0.5 to 2 m/s was measured and used to calculate dP/dt by the simplified Bernoulli equation. Baseline demographics, right heart catheterization measurements, and clinical outcomes of RVF failure and mortality were obtained by chart review. Presence and severity of RVF was based on current INTERMACS criteria. Non-parametric Mann-Whitney U test was used to compare groups that had mild or no RVF vs those that had moderate or severe RVF. Results From a total of 60 patients, 39 had TTE performed while off inotropic support and 23 had an adequate TR Doppler signal for analysis. Moderate or severe RVF was present in 10/23 (43%) of patients with average dP/dt 233 ± 58 mmHg/sec. The remaining 13/23 had mild or no RVF with an average dP/dt 314 ± 93 mmHg (p = 0.036). Pre-operative tricuspid annular plane systolic excursion (TAPSE), RV free wall tissue Doppler velocity (s’), RV fractional area change, pulmonary artery pulsatility index (PAPi), and the ratio of central venous pressure to pulmonary capillary wedge pressure (CVP/PCWP) ratio did not significantly differ between groups (Figure 1). Of note, no patients with dP/dt greater than 325 mmHg/sec had moderate or severe RVF. Conclusions TTE derived RV dP/dt strongly correlates with post LVAD RVF, and when greater than 325 mmHg/sec identifies those at low risk for RVF. Future prospective studies are needed to determine if this TTE measurement independently predicts a favorable outcome in LVAD patients.

Exposure to rare diagnoses during imaging rotations in cardiovascular (CV) fellowship can be unevenly distributed. An evaluation of our imaging curriculum showed 65% of CV fellows were uncomfortable recognizing rare diagnoses on imaging modalities (echocardiography, computed tomography (CT)

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.

Preamble 1523 1. Introduction 1524 2. General Standards 1526 3. Training Components 1526 4. Training Requirements 1528 5. Evaluation of Proficiency 1542 6. Maintenance of Competency 1543 References 1543 Appendix 1. Author Relationships with Industry and Other Entities (Relevant) 1545 Appendix 2. Reviewer Relationships with Industry and Other Entities (Relevant) 1548 Appendix 3. Abbreviations 1551 Since the 1995 publication of its Core Cardiovascular Training Statement (COCATS), the American College of Cardiology (ACC) has played a central role in defining …

1.1 Document Development Process #### 1.1.1 Writing Committee Organization The writing committee was selected to represent the American College of Cardiology (ACC) and included a cardiovascular training program director, an early-career cardiologist, highly experienced members representing

Background— Activation of cellular Ca 2+ signaling molecules appears to be a fundamental step in the progression of cardiomyopathy and arrhythmias. Myocardial overexpression of the constitutively active Ca 2+ -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 Ca 2+ -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.

Objective To determine the characteristics and prognostic importance of right ventricular (RV) dilatation and dysfunction in patients with cardiogenic shock secondary to left ventricular (LV) dysfunction enrolled in the Should we emergently revascularize occluded coronaries for cardiogenic shock (SHOCK) trial. Methods LV and RV size and function were quantified by echocardiography in 99 patients with cardiogenic shock secondary to predominant LV dysfunction. Results For all patients, RV dysfunction was not associated with a poor 1-year survival. When the 59 patients with RV dysfunction were stratified into two morphologic groups based upon LV-to-RV end-diastolic area ratio (LV/RV) < or ≥ 2, the presence of disproportionate RV enlargement (LV/ RV

OBJECTIVES The purpose of this study was to determine the characteristics and outcomes of patients with acute myocardial infarction (MI) complicated by cardiogenic shock due to predominant right ventricular (RV) infarction. BACKGROUND Although RV infarction has been shown to have favorable long-term outcomes, the influence of RV infarction on mortality in cardiogenic shock is unknown. METHODS We evaluated 933 patients in cardiogenic shock due to predominant RV (n = 49) or left ventricular (LV) failure (n = 884) in the SHould we emergently revascularize Occluded coronaries for Cardiogenic shocK? (SHOCK) trial registry. RESULTS Patients with predominant RV shock were younger, with a lower prevalence of previous MI (25.5 vs. 40.1%, p = 0.047), anterior MI, and multivessel disease (34.8 vs. 77.8%, p < 0.001) and a shorter median time between the index MI and the diagnosis of shock (2.9 vs. 6.2 h, p = 0.003) in comparison to patients with LV shock. In-hospital mortality was 53.1% versus 60.8% (p = 0.296) for patients with predominant RV and LV shock, respectively, and the influence of revascularization on mortality was not different between groups. Multivariate analysis revealed that RV shock was not an independent predictor of lower in-hospital mortality (odds ratio 1.07, 95% confidence interval 0.54 to 2.13). CONCLUSIONS Despite the younger age, lower rate of anterior MI, and higher prevalence of single-vessel coronary disease of RV compared with LV shock patients, and their similar benefit from revascularization, mortality is unexpectedly high in patients with predominant RV shock and similar to patients with LV shock.

Introduction: Takotsubo’s cardiomyopathy, or stress induced cardiomyopathy, is characterized by transient wall-motion abnormalities involving the left ventricular apex and mid-ventricle in the absence of obstructive epicardial coronary disease. It is seen more commonly in post-menopausal women and is usually preceded by an acute medical illness or intense emotional or physical stress. While the Mayo Criteria for the classification of Takotsubo’s cardiomyopathy involves the absence of epicardial coronary disease, up to 10% of patients have been found to have concurrent significant coronary artery disease. Conclusions: We present a case of a patient who presented with seizures and was found to have ST elevations, elevated cardiac enzymes and a new cardiomyopathy. While it was discovered that she had severe coronary disease of her LAD and RCA, the true nature of her cardiomyopathy and presentation was a stress-induced cardiomyopathy in the setting of seizure. The accuracy of this diagnosis affected the prognosis and treatment options for our patient. Cardiac MRI, and specifically the presence or absence of late gadolinium enhancement, helped differentiate the etiology of her cardiomyopathy. With the increasing prevalence of coronary disease, we will likely see more cases such as these in the future and should continue to evolve our definition and tools for the diagnosis of an increasing and interesting phenomenon.

Background The degree of aortic insufficiency (AI) after transcatheter aortic valve replacement (TAVR) has been identified as a predictor of increased mortality. Since even mild AI is associated with increased mortality in some studies, accurate quantification of post-TAVR AI is critical. Assessment of AI by echocardiography is typically performed by visual inspection and semi-quantitative methods. Most post-TAVR AI is paravalvular, however echocardiography has limited ability to quantify multiple eccentric paravalvular jets. Using flow quantification methods, cardiac MRI (CMR) may more accurately quantify AI severity post-TAVR and therefore more accurately assess risk in this population. Methods Twenty-three patients who underwent TAVR with a SAPIEN prosthesis were studied. All patients underwent an intraoperative transesophageal echocardiogram (TEE), as well as a post-procedure transthoracic echocardiogram (TTE) and CMR. Paravalvular AI by TTE and TEE was graded using color Doppler by quantifying the circumferential extent of AI as a percentage of the aortic annulus (none 30%) following recommendations from the Valve Academic Research Consortium. AI severity by CMR was quantified as the regurgitant fraction of forward aortic flow based on previously published recommendations (none 48%). Results The mean age was 79 +/- 10 years; 52% were men. TTE and CMR were performed at 1 [1-1] and 4 [1-4] days postTAVR respectively (median [IQR]). The left ventricular ejection fraction (LVEF) by CMR was 65 +/- 10%. AI severity by TTE was none in 9 (39.1%), trace in 11 (47.8%), and mild in 3 (13%) patients. TEE identified trace central AI in 6 patients (26%). Paravalvular AI by TEE was none in 4 (17.4%), trace in 14 (60.9%), and mild in 5 (21.7%) patients. AI by CMR was none in 2 (8.7%), trace in 5 (21.7%), mild in 13 (56.5%), and moderate in 3 (13%) patients; (Figure 1). A higher proportion of patients with mild or greater AI was identified by CMR (16/23, 70%) compared to TTE (3/23, 13%) and TEE (5/23, 22%); (Figure 2). Conclusions

Knowledge of left-sided cardiac filling pressures has an important role in the management of patients with chronic heart failure. However, the use of a pulmonary artery catheter to measure pulmonary capillary wedge pressure is generally reserved for hospitalized patients with decompensated heart failure, leaving only noninvasive means of estimating left heart pressures in the majority of patients. Unfortunately, the routine clinical evaluation of patients with chronic systolic heart failure lacks the sensitivity and specificity needed to accurately assess left atrial pressure. In this review, we focus on noninvasive methods that can reliably predict left-sided filling pressures and may have clinical application in the ambulatory setting.

Background Remodeling of the left ventricle with the development of a spherical cavity occurs in dilated cardiomyopathy and is associated with a poor long-term prognosis. The early effects of myocarditis on left ventricular geometry have not been previously described or correlated with clinical outcome. Methods The baseline echocardiograms of 35 patients with biopsy-confirmed myocarditis were compared with 20 normal controls. Left ventricular end-diastolic volume, long axis length, and mid-cavity diameter were measured. The degree of sphericity was expressed as the ratio of the mid-cavity diameter to the long axis length. Left ventricular ejection fraction was assessed by radionuclide angiography. Results In patients with myocarditis, mean left ventricular volume of 81 ± 29 mL/m 2 was significantly greater than 50 ± 8 mL/m 2 in controls ( P = .001). Chamber dilatation occurred primarily along the mid-cavity diameter, which measured 5.3 ± 0.8 cm in patients with myocarditis versus 4.2 ± 0.4 cm in controls ( P = .001). The degree of left ventricular sphericity in patients with myocarditis, 0.64 ± 0.08, was significantly greater than that of controls, 0.54 ± 0.04 ( P = .001). When patients were stratified according to left ventricular volume, patients with increased left ventricular volume (>75 mL/m 2 ) were associated with a more spherical chamber and lower left ventricular ejection fraction than patients with a more normal left ventricular volume (≤75 mL/m 2 ). Conclusions Active myocarditis is associated with early left ventricular remodeling and the development of a spherical chamber. These changes correlate with ventricular dilatation and reduced left ventricular ejection fraction. (Am Heart J 1999;138:303-8.)

This study was designed to characterize the geometry and function of the right ventricle and its prognostic significance in patients with primary (AL) cardiac amyloidosis. AL amyloidosis is an infiltrative systemic disease that can result in thickening of heart structures and rapidly progressive congestive heart failure due to restrictive ventricular physiology and eventual systolic dysfunction. Thirty-seven patients with AL amyloid heart involvement and 20 normal control subjects were evaluated using 2-dimensional and Doppler echocardiography. Based on the ratio of left-to-right end-diastolic ventricular chamber areas, patients were classified into 2 groups: 25 patients with disproportionate right ventricular (RV) dilation (left ventricular to RV ratio 2. Patients with a relatively dilated right ventricle (ratio 2 (10 months, p

Background The role of transesophageal echocardiography (TEE) simulation in cardiology fellows' learning is unknown. Standard TEE training at the authors' institution occurs during the second of 3 clinical years. Fellows spend 2 months in the TEE laboratory learning through hands-on experience. The addition of TEE simulation to this experience may improve proficiency, speed learning, and increase fellows' comfort with TEE. This study was designed to compare methods of TEE simulator training with standard training. Methods Group A ( n = 8) consisted of fellows who had completed standard TEE training. Fellows starting their second clinical year were randomly assigned to group B ( n = 10), simulator training during month 1, or group C ( n = 9), simulator training during month 2. All groups completed 2 months of standard TEE training. All groups underwent assessment of TEE performance and a self-assessment of ability and comfort level with TEE. Results Groups B and C had higher total assessment scores than group A. Groups B and C had higher numbers of views achieved without assistance ( P = .01). After month 1, group B had higher total scores and number of views achieved without assistance compared with group C ( P = .02 and P = .02, respectively). The length of time of the examination tended to be lower for group B, and fellows in group B had greater comfort with TEE than those in group C ( P = .01). Conclusions These data suggest that TEE simulator training improves proficiency and helps speed learning and comfort with TEE.

Left-sided mechanical valve thrombosis typically presents with acute heart failure symptoms and can rapidly progress to cardiogenic shock. However, subacute valvular thrombosis can have a more insidious course. A 51 year old woman with prior mechanical aortic (19 mm bileaflet) and mitral valve (29

Objectives. This study attempted to determine the importance of severe proximal right coronary artery disease as a predictor of atrial fibrillation in patients after coronary artery bypass surgery.Background. Studies in patients undergoing noncardiac surgery have suggested that ischemia in the right coronary artery distribution is associated with a high incidence of atrial fibrillation. However, the importance of right coronary artery disease as a predictor of atrial fibrillation after bypass surgery is unknown.Methods. The occurrence of sustained postoperative atrial fibrillation was studied prospectively in 168 consecutive patients undergoing coronary artery bypass grafting. Patients were followed up postoperatively until discharge. Severe right coronary artery stenosis was defined as ≥70% lumen narrowing.Results. Of 104 patients with proximal or mid right coronary artery stenosis, 45 (43%) had atrial fibrillation postoperatively compared with 12 (19%) of the 64 patients without significant right coronary disease (p = 0.001). Univariate predictors of atrial fibrillation included right coronary artery stenosis (p = 0.001), advancing age (p = 0.0001) and lack of beta-adrenergic blocking agent therapy after bypass surgery (p = 0.0004). Multivariate adjusted risk of developing atrial fibrillation after bypass surgery increased with the presence of severe right coronary artery disease (odds ratio 3.69, 95% confidence interval [CI] 1.61 to 8.48), advancing age (odds ratio 2.24/10 years, CI 1.48 to 3.41) and male gender (odds ratio 2.36, CI 1.01 to 5.49). The use of beta-blockers postoperatively was associated with a protective effect (odds ratio 0.4, CI 0.17 to 0.80).Conclusions. The presence of severe right coronary artery stenosis is an independent and powerful predictor of atrial fibrillation after coronary artery bypass surgery. In association with age, gender and postoperative beta-blocker therapy, these variables can be used to identify patients at increased risk for developing this arrhythmia.

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.

Objectives . The aim of this study was to assess the incidence and severity of left ventricular diastolic dysfunction immediately after coronary artery bypass surgery by utilizing simultaneous transesophageal echocardiographic and hemodynamic monitoring. Background . Left ventricular diastolic dysfunction has been documented after coronary bypass surgery, but its measurement has been technically difficult to acquire and limited by dependence on loading conditions. Methods . End-diastolic pressure-area curves were constructed before and immediately after coronary bypass surgery in 20 patients. Transesophageal echocardiographic images at the mid-papillary level of the left ventricle and hemodynamic data were recorded. Volume status was manipulated to alter loading conditions, and muitiple measurements were taken at each loading condition. Results . Diastolic function worsened in all patients, as manifested by a postoperative leftward shift of the end-diastolic pressure-area curve. At a comparable preload, mean end-diastolic area ± SEM decreased by 15% from 17.6 ± 0.8 to 14.9 ± 0.8 cm 2 postoperatively (p = 0.0001). Conclusions . Left ventricular diastolic chamber stiffness frequently increases immediately after coronary artery bypass surgery. Simultaneous hemodynamic and transesophageal echocardiographic monitoring, through the construction of end-diastolic pressure-area curves, is a useful method to evaluate diastolic function and guide management after cardiac surgery.

To assess the predictive value of right ventricular systolic function in patients with active myocarditis, the echocardiograms of 23 patients with biopsy-confirmed myocarditis were reviewed. Right ventricular systolic function was evaluated qualitatively and quantitatively by descent of the right ventricular base. Patients were divided into those with normal right ventricular function, in whom right ventricular descent was 1.9 +/- 0.1 cm, and those with abnormal right ventricular function, in whom right ventricular descent was 0.8 +/- 0.1 cm (p0.001). There were no differences between the two groups in age, duration of symptoms, baseline hemodynamics, or histologic assessment. Initial left ventricular ejection fraction was significantly lower in patients with depressed right ventricular function (27.5 +/- 4.9%) compared with that in patients with normal right ventricular function (47.5 +/- 6.3%) (p = 0.01). The likelihood of an adverse outcome, defined as death or need for cardiac transplantation, was greater in patients with abnormal right ventricular function (right ventricular descentor = 1.7 cm) than in patients with normal right ventricular function (right ventricular descent1.7 cm) (p0.03). Multivariate analysis revealed that right ventricular dysfunction as quantified by right ventricular descent was the most powerful predictor of adverse outcome.

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.