Faculty Bibliography

BACKGROUND:Ivabradine is guideline-recommended to reduce heart failure (HF) hospitalization in patients with stable chronic HF with reduced ejection fraction (EF). Ivabradine initiation following acute HF has had limited evaluation, and there are few randomized data in US patients. The PredischaRge initiation of Ivabradine in the ManagEment of Heart Failure (PRIME-HF) study was conducted to address predischarge ivabradine initiation in stabilized acute HF patients. METHODS:PRIME-HF was an investigator-initiated, randomized, open-label study of predischarge initiation of ivabradine versus usual care. Eligible patients were hospitalized for acute HF but stabilized, with EF ≤35%, on maximally tolerated β-blocker and in sinus rhythm with heart rate ≥70 beats/min. Ivabradine was acquired per routine care. The primary end point was the proportion of patients on ivabradine at 180 days. Additional end points included heart rate change, patient-reported outcomes, β-blocker use/dose, and safety events (symptomatic bradycardia and hypotension). RESULTS:Overall, 104 patients (36% women, 64% African American) were randomized, and the study was terminated early because of funding limitations. At 180 days, 21 of 52 (40.4%) of patients randomized to predischarge initiation were treated with ivabradine compared with 6 of 52 (11.5%) randomized to usual care (odds ratio 5.19, 95% CI 1.88-14.33, P = .002). The predischarge initiation group experienced greater reduction in heart rate through 180 days (mean -10.0 beats/min, 95% CI -15.7 to -4.3 vs 0.7 beats/min, 95% CI -5.4 to 6.7, P = .011). Patient-reported outcomes, β-blocker use/dose, and safety events were similar (all P > .05). CONCLUSIONS:Ivabradine initiation prior to discharge among stabilized HF patients increased ivabradine use at 180 days and lowered heart rates without reducing β-blockers or increasing adverse events. As the trial did not achieve the planned enrollment, additional studies are needed.

OBJECTIVES/OBJECTIVE:The aim of this study was to compare, using results from the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, the incremental cost-effectiveness of a stress cardiovascular magnetic resonance (CMR)-first strategy against 4 other clinical strategies for patients with stable symptoms suspicious for myocardial ischemia: 1) immediate x-ray coronary angiography (XCA) with selective fractional flow reserve for all patients; 2) single-photon emission computed tomography; 3) coronary computed tomographic angiography with selective computed tomographic fractional flow reserve; and 4) no imaging. BACKGROUND:Stress CMR perfusion imaging has established excellent diagnostic utility and prognostic value in coronary artery disease (CAD), but its cost-effectiveness in current clinical practice has not been well studied in the United States. METHODS:A decision analytic model was developed to project health care costs and lifetime quality-adjusted life years (QALYs) for symptomatic patients at presentation with a 32.4% prevalence of obstructive CAD. Rates of clinical events, costs, and quality-of-life values were estimated from SPINS and other published research. The analysis was conducted from a U.S. health care system perspective, with health and cost outcomes discounted annually at 3%. RESULTS:Using hard cardiovascular events (cardiovascular death or acute myocardial infarction) as the endpoint, total costs per person were lowest for the no-imaging strategy ($16,936) and highest for the immediate XCA strategy ($20,929). Lifetime QALYs were lowest for the no-imaging strategy (12.72050) and highest for the immediate XCA strategy (12.76535). The incremental cost-effectiveness ratio for the CMR-based strategy compared with the no-imaging strategy was $52,000/QALY, whereas the incremental cost-effectiveness ratio for the immediate XCA strategy was $12 million/QALY compared with CMR. Results were sensitive to variations in model inputs for prevalence of disease, hazard rate ratio for treatment of CAD, and annual discount rate. CONCLUSIONS:Prior to invasive XCA, stress CMR can be a cost-effective gatekeeping tool in patients at risk for obstructive CAD in the United States. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891.

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.

INTRODUCTION:The Electronic Health Record (EHR) has become an integral component of healthcare delivery. Survey based studies have estimated that physicians spend 4-6 hours of their workday devoted to EHR. Our study was designed to use computer software to objectively obtain time spent on EHR. METHODS:We recorded EHR time for 248 physiciansover 2 time intervals. EHR active use was defined as more than 15 keystrokes, or 3 mouse clicks, or 1700 "mouse miles" per minute. We recorded total time and % of work hours spent on EHR, and differences in those based on seniority. Physicians reported duty hours using a standardized toolkit. RESULTS:Physicians spent 3.8 (±2) hours on EHR daily, which accounted for 37% (±17%), 41% (±14%), and 45% (±12%) of their day for all clinicians, residents, and interns, respectively. With the progression of training, there was a reduction in EHR time (all p values <0.01). During the first academic quarter, clinicians spent 38% (± 8%) of time on chart review, 17% (± 7%) on orders, 28% (±11%) on documentation (i.e. writing notes) and 17% (±7%) on other activities (i.e. physician hand-off and medication reconciliation). This pattern remained unchanged during the fourth quarter. CONCLUSIONS:Physicians spend close to 40% of their work day on EHR, with interns spending the most time. There is a significant reduction in time spent on EHR with training and greater experience, although the overall amount of time spent on EHR remained high.

BACKGROUND:Stress cardiac magnetic resonance (CMR) provides accurate assessment of both myocardial infarction (MI) and ischemia. OBJECTIVES:This study aimed to evaluate the incremental prognostic value of unrecognized myocardial infarction (UMI), detected during assessment of coronary artery disease (CAD) by stress CMR, beyond cardiac function and ischemia. METHODS:In the multicenter SPINS (Stress CMR Perfusion Imaging in the United States) study, 2,349 consecutive patients (63 ± 11 years of age, 53% were male) with suspected CAD were assessed by stress CMR and followed over a median of 5.4 years. UMI was defined as the presence of late gadolinium enhancement consistent with MI in the absence of medical history of MI. This study investigated the association of UMI with all-cause mortality and nonfatal MI (death and/or MI), and major adverse cardiac events (MACE). RESULTS:UMI was detected in 347 patients (14.8%) and clinically recognized myocardial infarction (RMI) in 358 patients (15.2%). Compared with patients with RMI, patients with UMI had a similar burden of cardiovascular risk factors, but significantly lower left ventricular ejection fraction (p < 0.001) and lower rates of guideline-directed medical therapies, including aspirin (p < 0.001), statin (p < 0.001), and beta-blockers (p = 0.002). During follow-up, 328 deaths and/or MIs and 528 MACE occurred. In univariate analysis, UMI and RMI were strongly associated with death and/or MI (UMI: hazard ratio [HR]: 2.15; 95% confidence interval [CI]: 1.63 to 2.83; p < 0.001; RMI: HR: 2.45; 95% CI: 1.89 to 3.18) and MACE. Compared with patients with RMI, patients with UMI presented an increased risk for heart failure hospitalization (UMI vs. RMI: HR: 2.60; 95% CI: 1.48 to 4.58; p < 0.001). In a multivariate model including ischemia and left ventricular ejection fraction, UMI and RMI maintained robust prognostic association with death and/or MI (UMI: HR: 1.82; 95% CI: 1.37 to 2.42; p < 0.001; RMI: HR: 1.54; 95% CI: 1.14 to 2.09) and MACE. CONCLUSIONS:In a multicenter cohort of patients with suspected CAD, presence of UMI or RMI portended an equally significant risk for death and/or MI, independently of the presence of ischemia. Compared with RMI patients, those with UMI were less likely to receive guideline-directed medical therapies and presented an increased risk for heart failure hospitalization that warrants further study. (Stress CMR Perfusion Imaging in the United States [SPINS]; NCT03192891).

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).

OBJECTIVES:The goal of this study was to evaluate the prognostic value of global longitudinal strain (GLS) derived from cardiac magnetic resonance (CMR) feature-tracking in a large multicenter population of patients with preserved ejection fraction. BACKGROUND:Ejection fraction is the principal parameter used clinically to assess cardiac mechanics and provides prognostic information. However, significant abnormalities of myocardial deformation can be present despite preserved ejection fraction. CMR feature-tracking techniques now allow assessment of strain from routine cine images, without specialized pulse sequences. Whether abnormalities of strain measured by using CMR feature-tracking have prognostic value in patients with preserved ejection fraction is unknown. METHODS:Consecutive patients with preserved ejection fraction (≥50%) and a clinical indication for CMR at 4 U.S. medical centers were included in this retrospective study. Feature-tracking GLS was calculated from 3 long-axis cine views. The primary endpoint was all-cause death. Cox proportional hazards regression modeling was used to examine the independent association between GLS and death. The incremental prognostic value of GLS was assessed in nested models. RESULTS:Of the 1,274 patients in this study, 115 died during a median follow-up of 6.2 years. By Kaplan-Meier analysis, patients with GLS ≥ median (-20%) had significantly reduced event-free survival compared with those with GLS < median (log-rank test, p < 0.001). By Cox multivariable regression modeling, each 1% worsening in GLS was associated with a 22.8% increased risk of death after adjustment for clinical and imaging risk factors (hazard ratio: 1.228 per percent; p < 0.001). Addition of GLS in this model resulted in significant improvement in the global chi-square test (94 to 183; p < 0.001) and Harrell's C-statistic (0.75 to 0.83; p < 0.001). CONCLUSIONS:GLS derived from CMR feature-tracking is a powerful independent predictor of mortality in patients with preserved ejection fraction, incremental to common clinical and imaging risk factors.

OBJECTIVES/OBJECTIVE:The aim of this study was to investigate the prognostic value of stress cardiac magnetic resonance imaging (CMR) in patients with reduced left ventricular (LV) systolic function. BACKGROUND:Patients with ischemic cardiomyopathy are at risk from both myocardial ischemia and heart failure. Invasive testing is often used as the first-line investigation, and there is limited evidence as to whether stress testing can effectively provide risk stratification. METHODS:In this substudy of a multicenter registry from 13 U.S. centers, patients with reduced LV ejection fraction (<50%), referred for stress CMR for suspected myocardial ischemia, were included. The primary outcome was cardiovascular death or nonfatal myocardial infarction. The secondary outcome was a composite of cardiovascular death, nonfatal myocardial infarction, hospitalization for unstable angina or congestive heart failure, and unplanned late coronary artery bypass graft surgery. RESULTS:Among 582 patients (mean age 62 ± 12 years, 34% women), 40% had a history of congestive heart failure, and the median LV ejection fraction was 39% (interquartile range: 28% to 45%). At median follow-up of 5.0 years, 97 patients had experienced the primary outcome, and 182 patients had experienced the secondary outcome. Patients with no CMR evidence of ischemia or late gadolinium enhancement (LGE) experienced an annual primary outcome event rate of 1.1%. The presence of ischemia, LGE, or both was associated with higher event rates. In a multivariate model adjusted for clinical covariates, ischemia and LGE were independent predictors of the primary (hazard ratio [HR]: 2.63; 95% confidence interval [CI]: 1.68 to 4.14; p < 0.001; and HR: 1.86; 95% CI: 1.05 to 3.29; p = 0.03) and secondary (HR: 2.14; 95% CI: 1.55 to 2.95; p < 0.001; and HR 1.70; 95% CI: 1.16 to 2.49; p = 0.007) outcomes. The addition of ischemia and LGE led to improved model discrimination for the primary outcome (change in C statistic from 0.715 to 0.765; p = 0.02). The presence and extent of ischemia were associated with higher rates of use of downstream coronary angiography, revascularization, and cost of care spent on ischemia testing. CONCLUSIONS:Stress CMR was effective in risk-stratifying patients with reduced LV ejection fractions. (Stress CMR Perfusion Imaging in the United States [SPINS] Study; NCT03192891).

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.