Discovery and care innovation amidst a pandemic.

This article refers to ‘In‐hospital care in acute heart failure during the COVID‐19 pandemic: insights from the German‐wide Helios hospital network’ by S. König

The coronavirus disease 2019 (COVID‐19) pandemic has resulted in marked shifts in care delivery globally. While the direct effects of infection with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) have led to devastating loss of life and significant morbidity among survivors, the pandemic's effects may be longstanding and extend far beyond those who contract infection with SARS‐CoV‐2. In addition to consequences of the pandemic on employment, economic vitality, and mental health, the pandemic may also have important implications for access and desire to seek care for patients with chronic high‐risk illness, including heart failure.

In this issue of the Journal, König et al. examined hospitalization rates and in‐hospital outcomes for patients admitted to 67 German hospitals during the COVID‐19 pandemic. In the context of this administrative analysis, the investigators find that the incidence of heart failure admissions was significantly lower during the pandemic as compared to historical controls. Despite similar patient characteristics and functional status, clinical outcomes were worse among patients admitted during the pandemic as compared with 2019 controls. In‐hospital mortality for patients hospitalized with heart failure was 7.3% during the pandemic, compared with 6.1% earlier in 2020 prior to the pandemic, and 6.0% based on a historical time‐matched control cohort from 2019. The findings of reduced hospitalizations are consistent with global observations across major cardiovascular conditions, including heart failure, stroke, and acute coronary syndromes. , , , While ecological factors such as lower ambient pollution and reduced access to high sodium fast food may in part contribute to these findings, these factors alone would be unlikely to account for the magnitude of reduction in hospitalization observed. These data, when paired with observations of increases in out‐of‐hospital cardiac arrests, suggest that patients may be delaying or deferring presentations for acute conditions due to concerns about the risk of infection with COVID‐19.

Among patients who were hospitalized with heart failure, the authors identified higher disease severity and mortality. These findings may be linked to delays in care leading to more advanced disease at presentation, compounded by shifts in care practices that may have placed higher thresholds for admission for non‐COVID‐19‐related illness during the pandemic. Initial limitations in access to timely outpatient care may have also led to delays in diagnosis of worsening heart failure. Despite presentations to care setting, capacity constraints may have limited the ability for hospitals to admit patients with lesser symptom severity, leading to re‐presentations as the disease process progressed. Finally, possible misclassified or undiagnosed comorbid COVID‐19 may have contributed to the higher in‐hospital death rates and greater illness severity observed in this analysis. This potential for misclassification was likely greatest in the early phases of the pandemic, when COVID‐19 testing resources remained limited and prior to the formal incorporation of the International Classification of Disease—10th Revision (ICD‐10) code identifying COVID‐19 within administration data. In light of these mechanisms, similar reductions in presentations with greater disease severity have been observed in other acute and chronic disease states. , Taken together, these data and others highlight the need for robust education efforts to encourage prompt presentation to care facilities for symptoms that require acute diagnotic evaluation and early management approaches to avoid associated morbidity and mortality. As the pandemic progresses and during subsequent waves, these efforts will remain a central priority to stem the indirect detrimental effects of the pandemic on high‐risk patients.

In contrast to the devastating direct and indirect toll of the COVID‐19 pandemic, 2019 and 2020 have been remarkable years for therapeutic discovery in heart failure (Figure  ). Incremental progress has expanded the number of therapeutic options available specifically for patients with heart failure with reduced ejection fraction. Three large, international randomized clinical trials evaluating sodium–glucose co‐transporter 2 inhibitors have demonstrated consistent findings of improved morbidity and mortality. , Trials evaluating the soluble guanylate cyclase stimulator, vericuguat, and the myosin activator, omecamtiv mecarbil , have also yielded positive results, despite smaller effect sizes and no improvement in cardiovascular death. A number of therapeutic evaluations are currently under active study, including corollary evaluations across similar therapeutic classes for patients with heart failure with preserved ejection fraction. In fact, the first two therapies for heart failure with preserved ejection fraction (spironolactone and sacubitril/valsartan) will be presented to the US Food and Drug Administration for formal regulatory review in December 2020.

Figure 1

Scientific advances in heart failure (HF) during the COVID‐19 pandemic. ACC, American College of Cardiology; AHA, American Heart Association; CMS, Centers for Medicare & Medicaid Services; CRDAC, Cardiovascular and Renal Drugs Advisory Committee; EMA, European Medicines Agency; FDA, US Food and Drug Administration; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction.

How do we translate these advances into practice in light of seismic shifts in care delivery caused by the COVID‐19 pandemic? A small silver lining of the pandemic has been an explosion in virtual care necessitated by the care disruptions that led to significantly curtailed services across healthcare organizations. Expanding adoption of these virtual care strategies has allowed providers to reach patients often in their own homes, inclusive of caretakers and family members. Patient, clinician, and health system adaptations has also been mirrored by increasing flexibility by regulatory authorities in evaluating imperfect emerging trial data. For instance, the US Food and Drug Administration has remained active in reviewing cardiometabolic therapies despite immense structural challenges during the pandemic. There exists now an opportunity to leverage the increasing familiarity and comfort among patients and providers alike in interacting in virtual care platforms to accelerate implementation of recent advances in heart failure discovery science. For example, virtual visits designed specifically to discuss heart failure medication optimization may improve uptake and titration of guideline‐directed medical therapies, which has been slow to progress in the context of traditional outpatient clinical visits alone. Remote navigator‐based strategies have already shown promise in augmenting guideline‐directed medical therapy use, and these efforts may be expanded in a virtual care environment to encompass medication education, monitoring, side effect and symptom management, and anticipatory guidance. Similar strategies utilizing virtual frameworks offer promise for more direct communications with high‐risk patients to identify and treat congestion at an early stage, particularly if paired with devices assessing haemodynamics, weight, and medication adherence. Similarly, for patients who ultimately require hospitalization for decompensations of heart failure, transitional visits could be readily employed using a virtual care model, allowing for timely follow‐up care with providers who participated in or are familiar with the details of the hospital admission. These efforts may improve continuity of care, ensure adequate monitoring if changes were made during hospitalization, and allow for better assessment of changes in clinical status.

In 2020, the devestating disruption in patient behaviour and health system activity related to COVID‐19 stands in stark contrast with remarkable advances in scientific discovery and progress in identifying new therapeutic options for patients living with heart failure. Investments in alternative virtual health platforms, innovative implementation efforts, and broad clinical commitment to maintaining care delivery will help to realize the potential of these dramatic advances in discovery science in heart failure.

Conflict of interest: A.S.B. reports speaking fees from Sanofi Pasteur and is supported by the National Heart, Lung, and Blood Institute T32 postdoctoral training grant T32HL007604. M.V. is supported by the KL2/Catalyst Medical Research Investigator Training award from Harvard Catalyst (NIH/NCATS Award UL 1TR002541), receives research grant support from Amgen and Boehringer Ingelheim, serves on advisory boards for Amgen, American Regent, AstraZeneca, Baxter Healthcare, Bayer AG, Boehringer Ingelheim, Cytokinetics, and Relypsa, and participates in clinical endpoint committees for studies sponsored by Galmed, Novartis, and the NIH.