Drug-Coated Balloons in the Management of Coronary Artery Disease.

Drug-coated balloons (DCBs) are specialized coronary devices comprised of a semicompliant balloon catheter with an engineered coating that allows the delivery of antiproliferative agents locally to the vessel wall during percutaneous coronary intervention. Although DCBs were initially developed more than a decade ago, their potential in coronary interventions has recently sparked renewed interest, especially in the United States. Originally designed to overcome the limitations of conventional balloon angioplasty and stenting, they aim to match or even improve upon the outcomes of drug-eluting stents without leaving a permanent implant. Presently, in-stent restenosis is the condition with the most robust evidence supporting the use of DCBs. DCBs provide improved long-term vessel patency compared with conventional balloon angioplasty and may be comparable to drug-eluting stents without the need for an additional stent layer, supporting their use as a first-line therapy for in-stent restenosis. Beyond the treatment of in-stent restenosis, DCBs provide an additional tool for de novo lesions for a strategy that avoids a permanent metal scaffold, which may be especially useful for the management of technically challenging anatomies such as small vessels and bifurcations. DCBs might also be advantageous for patients with high bleeding risk due to the decreased necessity for extended antiplatelet therapy, and in patients with diabetes and patients with diffuse disease to minimize long-stented segments. Further studies are crucial to confirm these broader applications for DCBs and to further validate safety and efficacy.

Making more of less: using divestitures to unlock pharmaceutical innovation.

Pharmaceutical managers have been encouraged to look to acquisitions and alliances for innovation. However, the literature warns that the capacity of a company to 'absorb' new knowledge is limited. Here, we introduce corporate divestitures as a tool for freeing up managerial attention. We build a sample of 349 companies, which announced 1784 divestitures and filed 63523 patents, over a 15-year period. We show that innovating companies that divest more produce more and improved patents, and those that divest to create corporate focus also produce more breakthroughs. In doing so, we introduce divestitures as an innovation tool, highlight the importance of the absorptive capacity of a company when discussing innovation, and add nuance to the discussion on external tools for innovation.

Introduction of a standardized protocol for cardiac risk assessment in candidates for liver transplant - A retrospective cohort analysis.

INTRODUCTION: Recommendations on non-invasive imaging to assess pre-operative cardiac risk among liver transplant candidates vary amongst societal guidelines and individual institutional practices. In 2018, a standardized pre-transplant coronary evaluation protocol was established at Beth Israel Deaconess Medical Center, Boston MA, to ensure appropriate and consistent pre-operative testing was performed. METHODS: All patients who underwent liver transplant evaluation between January 1st, 2016 and December 31st, 2019, were retrospectively analyzed and divided into three cohorts; before the introduction of the protocol (prior to 2018), initial protocol favoring invasive coronary angiography (ICA) (2018), and amended protocol favoring coronary computed tomography angiography (CCTA) (post-2018). We described clinical characteristics, candidacy for transplant, and cardiovascular complications during follow-up. As an unadjusted exploratory analysis, the Cochran-Armitage Exact Trend Test was used to examine univariate differences across time. RESULTS: A total of 462 patients underwent liver transplant evaluation during the study period. Among these, 218 (47.2%) patients underwent stress test, 50 (10.8%) underwent CCTA, and 68 (14.8%) underwent ICA. Across the three time periods, there was an increase in the proportion of CCTAs performed (3%, 6.3%, and 26.3% respectively; p <0.001) and proportion of patients diagnosed with obstructive CAD using CCTA (0%, 30%, and 51.4% respectively; p = 0.04). There was no significant difference in post-transplant cardiac complications among patients evaluated before 2018, during 2018, and after 2018 (5.9% vs. 5.6 vs. 6.0%; p=1.0). CONCLUSION: Our findings suggest it is reasonable to shift practice to a less invasive approach utilizing CCTA or nuclear stress testing when assessing liver transplant candidates at increased cardiovascular risk.

Outcomes following implantable cardioverter-defibrillator generator replacement in adults: A systematic review.

Randomized trials inform the use of implantable cardioverter-defibrillators (ICDs) for prevention of sudden cardiac death, yet management of patients considering ICD generator replacement procedures remains largely dependent on clinical judgment. Thus, we performed a systematic review of all studies evaluating outcomes associated with ICD generator replacement. We queried PubMed, Embase, Web of Science, and the Cochrane Database of Systematic Reviews for relevant studies with a prespecified search and adjudication strategy (PROSPERO registration number CRD42018100818) to evaluate outcomes including (1) survival; (2) clinical complications (eg, infection, hematoma); or (3) incidence of ICD therapy. From 1607 unique titles, 37 studies met inclusion criteria, describing outcomes for 238,949 patients. Procedural mortality was rare, but complications including reoperation (median 4.57%; range 0.38%-10.31%), infections (median 2.01%; range 0.03%-9.27%), and hematoma (median 1.22%, range 0.17%-2.53%) were observed in a small fraction of patients. Appropriate ICD therapy after generator replacement was common (median rate 23.03%; range 10.9%-31.4%), with an overall annualized event rate of 8.52% at median duration of follow-up of 32.4 months. Appropriate ICD therapy continued to occur at a significant annual rate even in patients who no longer met implantation criteria (5.27%) and in patients who never previously received ICD therapy (4.87%). This analysis of published observational data regarding ICD generator replacement procedures identifies relatively low risks of procedural complications and clinically meaningful rates of appropriate ICD therapies. These estimates may guide clinical decisions and inform the design of definitive trials.

Impact of an Outpatient Cardiology-managed Urgent Access and Observation Unit on Hospital Admissions.

INTRODUCTION: Alternatives to the emergency department (ED) for expedient and high-value team-based cardiology care for patients with chest pain, volume overload, palpitations, and other urgent, but not life-threatening cardiac conditions are lacking. Here, we report on the development of the Cardiac Direct Access Unit (CDAc), an ambulatory cardiology unit with exam rooms, observation bays, and an advanced heart failure clinic. METHODS: Patients referred to the CDAc are seen same-day by an attending cardiologist in a space independent from the ED. We performed a retrospective review of 1146 consecutive patients referred to the CDAc in its first year of operation. Among patients who were referred for urgent same-day evaluation, 60.1% were discharged home without observation. RESULTS: Among the patients observed or directly discharged from CDAc, 2.4% were readmitted within 30 days for a related symptom. The highest rate of readmission (7.5%) was for heart failure, which compares favorably with guidelines for readmission benchmarks. CONCLUSION: Our first year of data suggests that a cardiology-directed observation unit may serve as a high-value alternative to the ED for appropriately selected patients.

When more isn't merrier: pharmaceutical alliance networks and breakthrough innovation.

Strategic alliances, in particular strategic alliances with universities, are widely thought to be beneficial to the drug discovery process. However, the discussion of alliances and their effect has tended to focus on single alliances and has ignored the fact that firms tend to participate in multiple alliances simultaneously. Here, we show the importance of adopting a portfolio perspective of strategic alliances. We build a model of the U.S. pharmaceutical industry, and show how 2298 alliances, announced over a 15-year period, impact the alliance portfolios of 324 pharmaceutical firms, and how that, in turn, impacts the breakthrough innovations that these firms produce. In doing so, we show the stengths and benifits of strategic alliances, but we also show the dangers of adopting a more the merrier approach to strategic alliance making.

Left Ventricular Thrombus After Acute Myocardial Infarction: Screening, Prevention, and Treatment.

Importance: Left ventricular (LV) thrombus is a complication of acute myocardial infarction (MI) and is associated with systemic thromboembolism. With randomized clinical trials investigating the optimal antithrombotic regimen in patients with MI who require concomitant chronic anticoagulation and with the emergence of the direct-acting oral anticoagulants, treatment options for post-MI LV thrombus have become more complicated. Herein, we review the epidemiology, pathogenesis, diagnosis, prevention, and treatment of LV thrombus after acute MI. Observations: Contemporary epidemiologic data suggest the incidence of LV thrombus, detected using optimal imaging modalities, may be as high as 15% in patients with ST-segment elevation MI and up to 25% in patients with anterior MI. While a standard transthoracic echocardiogram is commonly used for screening, it is limited by low sensitivity for LV thrombus detection, necessitating the addition of contrast (unless contraindicated) and/or use of cardiac magnetic resonance imaging when pretest probability is high. To our knowledge, there are no existing randomized clinical trials evaluating the safety and efficacy of anticoagulation in the prevention or treatment of LV thrombus after MI, and clinicians must rely on available epidemiologic and trial-generated data from related entities to guide treatment. Randomized clinical trials have confirmed that triple therapy increases bleeding rates compared with less potent antithrombotic regimens after MI, and observational data suggest that triple therapy regimens may not prevent LV thrombus formation. On the other hand, if an LV thrombus is detected, anticoagulation is essential to prevent systemic thromboembolism. We offer 1 approach to treatment, grounded in the best available data. Conclusions and Relevance: Uncertainties remain regarding the optimal screening pathway, frequency of follow-up imaging, candidate selection for thromboprophylaxis, and treatment strategies for post-MI LV thrombus. Ongoing studies from related therapeutic areas of varying antithrombotic regimens will continue to inform the optimal approach to treatment; however, more dedicated study of this clinical conundrum is also needed.