Optimal background pharmacological therapy for heart failure patients in clinical trials: JACC review topic of the week

With the current landscape of approved therapies for heart failure (HF), there is a need to determine the role of a standard background therapy against which novel therapies are studied. The Heart Failure Collaboratory convened a multistakeholder group of clinical investigators, clinicians, patients, government representatives including U.S. Food and Drug Administration and National Institutes of Health participants, payers, and industry in March 2021 to discuss whether standardization of background drug therapy is necessary in clinical trials in patients with HF. The current paper summarizes the discussion and provides potential conceptual approaches, with a focus on therapies indicated for HF with reduced ejection fraction

Getting to the Heart of the Matter: An Overview of Cardiac Toxicity Related to Cancer Therapy

With the improvement in cancer survival, long-term cardiotoxicity has become an area of increased interest. Various cancer therapies, including chemotherapy and radiation therapy can lead to cardiac toxicities with both acute and chronic manifestations. Awareness and early recognition can lead to improvement in cardiac survival and patient outcomes. The focus of this review is to summarize the cancer therapy agents most often associated with cardiovascular side effects, highlighting their mechanism of action and strategies for surveillance and prevention

Effectiveness of an interprofessional patient safety team-based learning simulation experience on healthcare professional trainees

Abstract Background Although the American Council of Graduate Medical Education (ACGME) mandates formal education in patient safety, there is a lack of standardized educational practice on how to conduct patient safety training. Traditionally, patient safety is taught utilizing instructional strategies that promote passive learning such as self-directed online learning modules or didactic lectures that result in suboptimal learning and satisfaction. Methods During the summer of 2015, 76 trainees consisting of internal medicine interns and senior-level nursing students participated in an interactive patient safety workshop that used a flipped classroom approach integrating team based learning (TBL) and interprofessional simulated application exercises. Results Workshop trainees demonstrated an increase in knowledge specifically related to patient safety core concepts on the Team Readiness Assurance Test (TRAT) compared to the Individual Readiness Assurance Test (IRAT) (p = 0.001). Completion rates on the simulation application exercises checklists were high except for a few critical action items such as hand-washing, identifying barriers to care, and making efforts to clarify code status with patient. The Readiness for Interprofessional Learning Scale (RIPLS) subscale scores for Teamwork and Collaboration and Professional Identity were higher on the post-workshop survey compared to the pre-workshop survey, however only the difference in the Positive Professional Identity subscale was statistically significant (p = 0.03). A majority (90%) of the trainees either agreed that the safety concepts they learned would likely improve the quality of care they provide to future patients. Conclusions This novel approach to safety training expanded teaching outside of the classroom and integrated simulation and engagement in error reduction strategies. Next steps include direct observation of trainees in the clinical setting for team-based competency when it comes to patient safety and recognition of system errors

A Critical Appraisal of Short-Term End Points in Acute Heart Failure Clinical Trials

The prevalence of heart failure continues to grow, and this is accompanied by an increase in hospitalization for acute heart failure. Hospitalization for heart failure results in a trajectory shift of the syndrome and is associated with worsening outcomes, increased mortality risk, and high costs. Numerous clinical trials over the past 2 decades have had limited success, with no single agent shown to improve mortality risk. The lack of success is multifactorial and in part related to inadequate targets and end points selected for intervention, underscoring the need to better understand and define the pathophysiology of acute heart failure. To better inform future drug development, this review critically explores the short-term end points and outcomes that previous phase III acute heart failure trials have examined

Temporal trends in risk profiles among patients hospitalized for heart failure

BackgroundPostdischarge mortality following hospitalization for heart failure with reduced ejection fraction (HFrEF) has remained high and unchanged over the past 2 decades, despite effective therapies for HFrEF. We aimed to explore whether these patterns could in part be explained by changes in longitudinal risk profile and HF severity over time.MethodsAmong patients hospitalized for HF in the GWTG-HF registry from January 2005 to December 2018 with available data, we evaluated GWTG-HF and ADHERE risk scores, observing in-hospital mortality per-year. The risk profiles and outcomes were described overall and by subgroups based on ejection fraction (EF), diabetes mellitus (DM), sex, and age.ResultsOverall, 335,735 patients were included (50% HFrEF, 46% DM, 48% female, mean age 74 years). In-hospital mortality increased by 2.0% per year from 2005 to 2018. There was no significant change in mean GWTG-HF risk score overall or when stratified by EF groups (P = 0.46 HFrEF, p = 0.26 HF mid-range EF [HFmrEF], and P = 0.72 HF preserved EF [HFpEF]), age, sex, or presence of DM. The observed/expected ratio based on the GWTG-HF risk score was 0.93 (0.91-0.96), 0.83 (0.77-0.90), 0.92 (0.89-95) for HFrEF, HFmrEF, and HFpEF, respectively. Similar findings were seen when risk was assessed using ADHERE risk score.ConclusionsThere were no significant changes in average risk profiles among hospitalized HF patients over the study duration. These data do not support the notion that worsening risk profile explains the lack of improved outcomes despite therapeutic advances, underscoring the importance of aggressive implementation of guideline-recommended therapies and investigation of novel treatments

Heart Failure Risk Associated With Severity of Modifiable Heart Failure Risk Factors: The ARIC Study

There is an urgent need to improve heart failure (HF) prevention. Global cardiovascular health, as reflected by Life’s Simple 7, is linked to incident HF. However, the extent to which HF incidence might be mitigated by simultaneously optimizing the modifiable HF risk factors of hypertension, diabetes, and obesity has not been rigorously quantified

The Systematic Evaluation of Identifying the Infarct Related Artery Utilizing Cardiac Magnetic Resonance in Patients Presenting with ST-Elevation Myocardial Infarction

<div><p>Background</p><p>Identification of the infarct-related artery (IRA) in patients with STEMI using coronary angiography (CA) is often based on the ECG and can be challenging in patients with severe multi-vessel disease. The current study aimed to determine how often percutaneous intervention (PCI) is performed in a coronary artery different from the artery supplying the territory of acute infarction on cardiac magnetic resonance imaging (CMR).</p><p>Methods</p><p>We evaluated 113 patients from the Reduction of infarct Expansion and Ventricular remodeling with Erythropoetin After Large myocardial infarction (REVEAL) trial, who underwent CMR within 4±2 days of revascularization. Blinded reviewers interpreted CA to determine the IRA and CMR to determine the location of infarction on a 17-segment model. In patients with multiple infarcts on CMR, acuity was determined with T2-weighted imaging and/or evidence of microvascular obstruction.</p><p>Results</p><p>A total of 5 (4%) patients were found to have a mismatch between the IRA identified on CMR and CA. In 4/5 cases, there were multiple infarcts noted on CMR. Thirteen patients (11.5%) had multiple infarcts in separate territories on CMR with 4 patients (3.5%) having multiple acute infarcts and 9 patients (8%) having both acute and chronic infarcts.</p><p>Conclusions</p><p>In this select population of patients, the identification of the IRA by CA was incorrect in 4% of patients presenting with STEMI. Four patients with a mismatch had an acute infarction in more than one coronary artery territory on CMR. The role of CMR in patients presenting with STEMI with multi-vessel disease on CA deserves further investigation.</p></div

Diabetes Duration and Subclinical Myocardial Injury: The Atherosclerosis Risk in Communities Study (ARIC) ( )

Background Diabetes exerts adverse effects on the heart, and a longer diabetes duration is associated with greater heart failure risk. We studied diabetes duration and subclinical myocardial injury, as reflected by high-sensitivity cardiac troponin (hs-cTnT). Methods We analyzed 9052 participants without heart failure or coronary heart disease (mean age 63 years, 58% female, 21% Black, 15% with diabetes) at The Atherosclerosis Risk in Communities Study (ARIC) Visit 4 (1996 to 1998). Diabetes duration was calculated based on diabetes status at Visits 1 (1987 to 1989) through 4, or using self-reported age of diabetes diagnosis prior to Visit 1. We used multinomial logistic regression to determine the association of diabetes duration with increased (>= 14 ng/L) or detectable (>= 6 ng/L) Visit 4 hs-cTnT, relative to undetectable hs-cTnT, adjusted for demographics and cardiovascular risk factors. Results The prevalence of increased Visit 4 hs-cTnT was higher in persons with longer diabetes duration, from 12% for those with diabetes 0 to = 15 years (P for trend = 15 years associated with 9.29x higher risk (95% CI, 5.65-15.29) for increased hs-cTnT and 2.07x (95% CI, 1.24-3.16) for detectable hs-cTnT, compared to no diabetes. Conclusions Longer diabetes duration is strongly associated with subclinical myocardial injury. Interventional studies are needed to assess whether the prevention and delay of diabetes onset can mitigate early myocardial damage

Multiple Infarcts on CMR and CA.

<p>CMR with evidence of multiple infarcts in LAD, RCA, and LCx distribution (A-C). Angiography with high-grade stenosis in LCx and LAD, 100% stenosis RCA (D-F)</p