Faculty Bibliography

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.

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.

Heart failure (HF) and type 2 diabetes mellitus (T2DM) are both growing public health concerns contributing to major medical and economic burdens to society. T2DM increases the risk of HF, frequently occurs concomitantly with HF, and worsens the prognosis of HF. Several anti-hyperglycaemic medications have been associated with a concern for worse HF outcomes. More recently, the results of the EMPA-REG OUTCOME trial showed that the sodium-glucose co-transporter 2 (SGLT2) inhibitor empagliflozin was associated with a pronounced and precocious 38% reduction in cardiovascular mortality in subjects with T2DM and established cardiovascular disease [Correction added on 8 September 2017, after first online publication: "32%" in the previous sentence was corrected to "38%"]. These benefits were more related to a reduction in incident HF events rather than to ischaemic vascular endpoints. Several mechanisms have been put forward to explain these benefits, which also raise the possibility of using these drugs as therapies not only in the prevention of HF, but also for the treatment of patients with established HF regardless of the presence or absence of diabetes. Several large trials are currently exploring this postulate.

PURPOSE OF REVIEW:With the growing prevalence of heart failure, there is a particular need to develop new pharmacologic treatments that can improve outcomes. While there are several approved therapies for heart failure with reduced ejection fraction, there is currently no approved agent for those with preserved ejection fraction. The current review aimed to explore the utility of alternate endpoints to mortality and hospitalization. RECENT FINDINGS:There is increased interest in the use of alternative endpoints such as functional status and quality of life for heart failure drug development to focus on patients feeling better in addition to improving outcomes. This should ideally be measured using objective as well as subjective parameters. While mortality and hospitalization remain important endpoints for clinical trials in heart failure, other more patient-centered outcomes are attractive alternatives yet how to best incorporate these in a trial setting remains to be elucidated.

Heart Failure is a global epidemic, affecting approximately 5 million adults in the U.S.A. The cornerstone of contemporary pharmacological therapy targets the over activated renin-angiotensin-aldosterone and sympathetic autonomic systems. The 2016 focused pharmacologic update on the current Heart Failure Guidelines introduces the use of two newly approved regimens valsartan/sacubitril and ivabradine. Over the last two decades, guideline directed medical therapy has accomplished significant improvement in survival rates among heart failure patients; however these novel compounds were reported to exert additional mortality and morbidity benefits, in heart failure subpopulations with reduced ejection fraction.

The increasing burden and the continued suboptimal outcomes for patients with heart failure underlines the importance of continued research to develop novel therapeutics for this disorder. This can only be accomplished with successful translation of basic science discoveries into direct human application through effective clinical trial design and execution that results in a substantially improved clinical course and outcomes. In this respect, phase II clinical trials play a pivotal role in determining which of the multitude of potential basic science discoveries should move to the large and expansive registration trials in humans. A critical examination of the phase II trials in heart failure reveals multiple shortcomings in their concept, design, execution, and interpretation. To further a dialogue on the challenges and potential for improvement and the role of phase II trials in patients with heart failure, the Food and Drug Administration facilitated a meeting on October 17, 2016, represented by clinicians, researchers, industry members, and regulators. This document summarizes the discussion from this meeting and provides key recommendations for future directions.

Cancer and cardiovascular disease account for nearly half of all deaths in the US. The majority of cancer therapies are known to cause potential cardiac toxicity in some form. Patients with underlying cardiac disease are at a particularly increased risk for worse outcomes following cancer therapy. Most alarming is the potential for heart failure as a result of cancer treatment, which may lead to early disruption or withdrawal of life-saving cancer therapies and can potentially increase cardiovascular mortality. A multi-disciplinary cardio-oncology approach can improve outcomes through early surveillance, prevention and treatment strategies.

BACKGROUND: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). METHODS: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. RESULTS: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. CONCLUSIONS: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.