Faculty Bibliography

OBJECTIVES/OBJECTIVE:The purpose of this study was to assess whether the presence and extent of fibrosis changes over time in patients with nonischemic, dilated cardiomyopathy (DCM) receiving optimal medical therapy and the implications of any such changes on left ventricular ejection fraction (LVEF) and clinical outcomes. BACKGROUND:Myocardial fibrosis on cardiovascular magnetic resonance (CMR) imaging has emerged as important risk marker in patients with DCM. METHODS:In total, 85 patients (age 56 ± 15 years, 45% women) with DCM underwent serial CMR (median interval 1.5 years) for assessment of LVEF and fibrosis. The primary outcome was all-cause mortality; the secondary outcome was a composite of heart failure hospitalization, aborted sudden cardiac death, left ventricular (LV) assist device implantation, or heart transplant. RESULTS:On CMR-1, fibrosis (median 0.0 [interquartile range: 0% to 2.6%]) of LV mass was noted in 34 (40%) patients. On CMR-2, regression of fibrosis was not seen in any patient. Fibrosis findings were stable in 70 (82%) patients. Fibrosis progression (increase >1.8% of LV mass or new fibrosis) was seen in 15 patients (18%); 46% of these patients had no fibrosis on CMR-1. Although fibrosis progression was on aggregate associated with adverse LV remodeling and decreasing LVEF (40 ± 7% to 34 ± 10%; p < 0.01), in 60% of these cases the change in LVEF was minimal (<5%). Fibrosis progression was associated with increased hazards for all-cause mortality (hazard ratio: 3.4 [95% confidence interval: 1.5 to 7.9]; p < 0.01) and heart failure-related complications (hazard ratio: 3.5 [95% confidence interval: 1.5 to 8.1]; p < 0.01) after adjustment for clinical covariates including LVEF. CONCLUSIONS:Once myocardial replacement fibrosis in DCM is present on CMR, it does not regress in size or resolve over time. Progressive fibrosis is often associated with minimal change in LVEF and identifies a high-risk cohort.

AIMS/OBJECTIVE:Non-invasive assessment and risk stratification of coronary artery disease in patients with large body habitus is challenging. We aim to examine whether body mass index (BMI) modifies the prognostic value and diagnostic utility of stress cardiac magnetic resonance imaging (CMR) in a multicentre registry. METHODS AND RESULTS/RESULTS:The SPINS Registry enrolled consecutive intermediate-risk patients who presented with a clinical indication for stress CMR in the USA between 2008 and 2013. Baseline demographic data including BMI, CMR indices, and ratings of study quality were collected. Primary outcome was defined by a composite of cardiovascular death and non-fatal myocardial infarction. Of the 2345 patients with available BMI included in the SPINS cohort, 1177 (50%) met criteria for obesity (BMI ≥ 30) with 531 (23%) at or above Class 2 obesity (BMI ≥ 35). In all BMI categories, >95% of studies were of diagnostic quality for cine, perfusion, and late gadolinium enhancement (LGE) sequences. At a median follow-up of 5.4 years, those without ischaemia and LGE experienced a low annual rate of hard events (<1%), across all BMI strata. In patients with obesity, both ischaemia [hazard ratio (HR): 2.14; 95% confidence interval (CI): 1.30-3.50; P = 0.003] and LGE (HR: 3.09; 95% CI: 1.83-5.22; P < 0.001) maintained strong adjusted association with the primary outcome in a multivariable Cox regression model. Downstream referral rates to coronary angiography, revascularization, and cost of care spent on ischaemia testing did not significantly differ within the BMI categories. CONCLUSION/CONCLUSIONS:In this large multicentre registry, elevated BMI did not negatively impact the diagnostic quality and the effectiveness of risk stratification of patients referred for stress CMR.

Background: Non-ischemic cardiomyopathy (NICM) is a leading cause of reduced left ventricular ejection fraction (LVEF) and is associated with high mortality risk from progressive heart failure and arrhythmias. Myocardial scar on cardiovascular magnetic resonance imaging (CMR) is increasingly recognized as risk marker for adverse outcomes, however LV dysfunction remains the basis for determining a patient's eligibility for primary prophylaxis implantable cardioverter-defibrillator (ICD). We wanted to investigate the relationship of LVEF and scar to long term mortality and mode of death in a large cohort of patients with NICM. Methods: This study is a prospective, longitudinal outcomes registry of 1020 consecutive patients with NICM who underwent clinical CMR for the assessment of LVEF and scar at three centers. Results: During a median follow-up of 5.2 (IQR 3.8, 6.6) years 277 (27%) patients died. On survival analysis LVEF≤35% and scar were strongly associated with all-cause (log-rank test p=0.002 and p<0.001, respectively) and cardiac death (p=0.001 and p<0.001, respectively). While scar was strongly related to sudden cardiac death (SCD) (p=0.001), there was no significant association between LVEF≤35% and SCD-risk (p=0.57). On multivariable analysis including established clinical factors, LVEF and scar are independent risk-markers of all-cause and cardiac death. The addition of LVEF provided incremental prognostic value albeit insignificant discrimination improvement by C-statistic for all-cause and cardiac death, however no incremental prognostic value for SCD. Conversely, scar extent demonstrated significant incremental prognostic value and discrimination improvement for all three endpoints. On net reclassification analysis, the addition of LVEF resulted in no significant improvement for all-cause death 11.0% (95% CI -6.2-25.9%), cardiac death 9.8% (95% CI -5.7-29.3%), and SCD 7.5% (95% CI -41.2-42.9%). Conversely, the addition of scar extent resulted in significant reclassification improvement of 25.5% (95% CI 11.7-41.0%) for all-cause death, 27.0% (95% CI 11.6-45.2%) for cardiac death, and 40.6% (95% CI 10.5-71.8%) for SCD. Conclusions: Myocardial scar and LVEF are both risk markers for all-cause and cardiac death in patients with NICM. However, while myocardial scar has strong and incremental prognostic value for SCD risk stratification, LVEF has no incremental prognostic value over clinical parameters. Scar assessment should be incorporated into patient selection criteria for primary prevention ICD placement.

Prosthetic valve endocarditis (PVE) represents 20% of all cases of endocarditis. Herein, we present a rare cause of PVE by Staphylococcus auricularis (S. auricularis) exhibiting features of subacute endocarditis causing severe aortic stenosis and acute myocardial infarction.

BACKGROUND:Hospitalization for acute decompensated heart failure (ADHF) remains a major source of morbidity and mortality. The current study aimed to investigate the feasibility, safety, and efficacy of outpatient furosemide intravenous (IV) infusion following hospitalization for ADHF. METHODS:In a single center, prospective, randomized, double-blind study, 100 patients were randomized to receive standard of care (Group 1), IV placebo infusion (Group 2), or IV furosemide infusion (Group 3) over 3h, biweekly for a one-month period following ADHF hospitalization. Patients in Groups 2/3 also received a comprehensive HF-care protocol including bi-weekly clinic visits for dose-adjusted IV-diuretics, medication adjustment and education. Echocardiography, quality of life and depression questionnaires were performed at baseline and 30-day follow-up. The primary outcome was 30-day re-hospitalization for ADHF. RESULTS:Overall, a total of 94 patients were included in the study (mean age 64 years, 56% males, 69% African American). There were a total of 14 (15%) hospitalizations for ADHF at 30 days, 6 (17.1%) in Group 1, 7 (22.6%) in Group 2, and 1 (3.7%) in Group 3 (overall p = 0.11; p = 0.037 comparing Groups 2 and 3). Patients receiving IV furosemide infusion experienced significantly greater urine output and weight loss compared to those receiving placebo without any significant increase creatinine and no significant between group differences in echocardiography parameters, KCCQ or depression scores. CONCLUSION/CONCLUSIONS:The use of a standardized protocol of outpatient IV furosemide infusion for a one-month period following hospitalization for ADHF was found to be safe and efficacious in reducing 30-day re-hospitalization.

Importance/UNASSIGNED:The role of stress cardiac magnetic resonance (CMR) imaging in clinical decision-making by reclassification of risk across American College of Cardiology/American Heart Association guideline-recommended categories has not been established. Objective/UNASSIGNED:To examine the utility of stress CMR imaging for risk reclassification in patients without a history of coronary artery disease (CAD) who presented with suspected myocardial ischemia. Design, Setting, and Participants/UNASSIGNED:A retrospective, multicenter cohort study with median follow-up of 5.4 years (interquartile range, 4.6-6.9) was conducted at 13 centers across 11 US states. Participants included 1698 consecutive patients aged 35 to 85 years with 2 or more coronary risk factors but no history of CAD who presented with suspected myocardial ischemia to undergo stress CMR imaging. The study was conducted from February 18, 2019, to March 1, 2020. Main Outcomes and Measures/UNASSIGNED:Cardiovascular (CV) death and nonfatal myocardial infarction (MI). Major adverse CV events (MACE) including CV death, nonfatal MI, hospitalization for heart failure or unstable angina, and late, unplanned coronary artery bypass graft surgery. Results/UNASSIGNED:Of the 1698 patients, 873 were men (51.4%); mean (SD) age was 62 (11) years, accounting for 67 CV death/nonfatal MIs and 190 MACE. Clinical models of pretest risk were constructed and patients were categorized using guideline-based categories of low (<1% per year), intermediate (1%-3% per year), and high (>3% year) risk. Stress CMR imaging provided risk reclassification across all baseline models. For CV death/nonfatal MI, adding stress CMR-assessed left ventricular ejection fraction, presence of ischemia, and late gadolinium enhancement to a model incorporating the validated CAD Consortium score, hypertension, smoking, and diabetes provided significant net reclassification improvement of 0.266 (95% CI, 0.091-0.441) and C statistic improvement of 0.086 (95% CI, 0.022-0.149). Stress CMR imaging reclassified 60.3% of patients in the intermediate pretest risk category (52.4% reclassified as low risk and 7.9% as high risk) with corresponding changes in the observed event rates of 0.6% per year for low posttest risk and 4.9% per year for high posttest risk. For MACE, stress CMR imaging further provided significant net reclassification improvement (0.361; 95% CI, 0.255-0.468) and C statistic improvement (0.092; 95% CI, 0.054-0.131), and reclassified 59.9% of patients in the intermediate pretest risk group (48.7% reclassified as low risk and 11.2% as high risk). Conclusions and Relevance/UNASSIGNED:In this multicenter cohort of patients with no history of CAD presenting with suspected myocardial ischemia, stress CMR imaging reclassified patient risk across guideline-based risk categories, beyond clinical risk factors. The findings of this study support the value of stress CMR imaging for clinical decision-making, especially in patients at intermediate risk for CV death and nonfatal MI.

OBJECTIVE:To describe from a non-interventional registry the short-term ischemic and hemorrhagic outcomes in patients with NSTEMI managed with a loading dose of a P2Y12 inhibitor (P2Y12i) given at least four hours prior to diagnostic angiography and delineation of coronary anatomy. Prior data on the effects of such "upstream loading" have been inconsistent. METHODS:In 53 US hospitals, we evaluated the in-hospital care and outcomes of patients with confirmed NSTEMI managed with an interventional strategy and loaded upstream (at least four hours before diagnostic angiography) with P2Y12 inhibitor therapy. Patients entered into the database were grouped into one of four cohorts for analysis: (1) overall cohort, (2) thienopyridine (clopidogrel or prasugrel) load, (3) ticagrelor load, and (4) ticagrelor-consistent. The fourth cohort is a subset of cohort 3 that received ticagrelor throughout the index hospital stay and at discharge. We evaluated in-hospital clinical course and ischemic and bleeding outcomes in all patients, and also 30-d outcomes in the ticagrelor-consistent cohort. RESULTS:A total of 3,355 patients were enrolled, of whom 1,087 had 30-day follow-up. The mean (+/-SD) age was 63.3+/-12.5 y and 62.6% were male. TIMI and GRACE scores placed these patients in the intermediate risk range and CRUSADE scores were in the moderate risk range. The loading dose in UPSTREAM was clopidogrel in 45.6%, ticagrelor in 53.6%, and prasugrel in 0.8%. The median upstream interval (loading dose to angiography) was 17:27 hours and did not change appreciably over the course of the data collection period (2/15 - 10/19). Access was radial in 48.6% and femoral in 51.4%. Post-angiography management was medical only in 32.3%, PCI in 59.4%, and CABG in 8.3%. Median LOS was 2.7d, and median time from angiography to CABG was 3.6d. In-hospital mortality was 0.51% and major bleeding (TIMI) was 0.24%; the in-hospital MACE rate was 0.7% and stent thrombosis occurred in 0.18%. No significant differences were seen between the ticagrelor and clopidogrel cohorts in hospital, but 16% received more than one P2Y12i in-hospital. On follow-up (93.2% response), 86.7% of patients reported taking ticagrelor as directed. CONCLUSION/CONCLUSIONS:Upstream loading of P2Y12 inhibitors was associated with very low rates of bleeding and short LOS in a large cohort of NSTEMI patients managed invasively.

OBJECTIVES/OBJECTIVE:This study analyzed changes in depressive symptoms in patients with heart failure and preserved ejection fraction (HFpEF) who were enrolled in the TOPCAT (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function) trial. BACKGROUND:There are limited longitudinal data for depressive symptoms in patients with HFpEF. METHODS:In patients enrolled in the United States and Canada (n = 1,431), depressive symptoms were measured using Patient Health Questionnaire-9 (PHQ-9). Clinically meaningful changes in PHQ-9 scores were defined as worse (≥3-point increase) or better (≥3-point decrease). Multivariate models were used to identify predictors of change in depressive symptoms. Cox proportional hazard models were used to determine the impact of symptom changes from baseline on subsequent incident cardiovascular events. RESULTS:At 12 months, 19% of patients experienced clinically worsening depressive symptoms, 31% better, and 49% unchanged. Independent predictors of clinically meaningful improvement in depressive symptoms included higher baseline PHQ-9 scores, male sex, lack of chronic obstructive pulmonary disease, and randomization to spironolactone. After data were adjusted for cardiovascular comorbidities, higher baseline PHQ-9 was associated with all-cause mortality (hazard ratio [HR]: 1.09; 95% confidence interval [CI]: 1.02 to 1.16; p = 0.011), whereas worsening depressive symptoms at 12 months were associated with cardiovascular death (HR: 2.47; 95% CI: 1.32 to 4.63; p = 0.005) and all-cause mortality (HR: 1.82; 95% CI: 1.13 to 2.93; p = 0.014). Randomization to spironolactone was associated with modest but statistically significant reduction in depressive symptoms over the course of the trial (p = 0.014). CONCLUSIONS:Higher baseline depressive symptoms and worsening depressive symptoms were associated with all-cause mortality. Randomization to spironolactone was associated with modest reduction in depressive symptoms. (Aldosterone Antagonist Therapy for Adults With Heart Failure and Preserved Systolic Function [TOPCAT]; NCT00094302).

Patients with acute nonspecific chest pain and low probability for coronary disease remain an important clinical management dilemma. We focus on evidence for imaging, in an integrated decision-making setting. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.