Treatment of Acute Heart Failure in the ED
Recent history suggests a grim future regarding the early management of AHF. Current treatment today largely mirrors treatment from 40 years ago and outcomes remain persistently poor. Attempts to develop novel therapies for AHF have largely failed. As the population ages, combined with continual improvements in cardiovascular care, more patients will have HF and the subsequent financial costs will also increase. Although new knowledge has been learned over the last 10 years, persistent efforts are needed to improve outcomes. Several themes are worth highlighting related to the future of AHF in the ED.
More than any other factor, admission rates contribute the most toward re-admission rates. In other words, baseline admission rates are the greatest predictor of re-admission; yet at the present time, efforts focus more on preventing re-admissions than index admissions and are more specialty based, rather than interdisciplinary. Although the scientific value of 30-day re-admissions is debated, it is likely that cost containment or the more politically correct term of 'value' will continue. Thus, EDs will come under greater scrutiny with regards to admission/discharge decisions. Yet, this is a potential opportunity for EDs to engage more deeply in the continuum of care.
This need to better understand the ED phase of management also applies to research. AHF patients are heterogenous; yet, treatment is largely homogenous. Classification of patients to better target treatment is appealing and intuitive, yet requires further study to determine whether such an approach improves outcomes. Classification helps generate hypotheses, however, as grouping might direct further inquiry into the underlying pathophysiology of AHF. Initial and intriguing attempts using biomarkers have already begun; more work is needed.
In addition to biomarkers, advanced imaging techniques and noninvasive hemodynamics are opportunities to better understand the structure, function and hemodynamic state of patients. It is a presumption that characteristics observed during hospitalization were present in the ED to the same degree. Although this may be true for some patients, there may be other subgroups where unique characteristics are observed in the ED that change with treatment. Specifically, echocardiography would allow for greater characterization of patients at the time of presentation. Importantly, serial exams may demonstrate changes over time, highlighting opportunities where intervention might alter the pathophysiologic trajectory of some patients.
Characterization of patients could also happen in reverse, where detailed clinical phenotypes are recorded and biological specimens are collected in order to be further analyzed at the 'omic' level. In addition to improved pathophysiologic understanding, new therapeutic targets might be identified. Generating hypotheses from real-world clinical observation requires robust interdisciplinary collaboration.
Improved clinical phenotyping would also allow for more selective patient inclusion for clinical studies or even 'guided' studies, where only patients with specific characteristics are included. For example, differentiating treatment based on the presence or absence of a novel biomarker. Other possibilities include continuation, escalation or withdrawal of treatment guided by either a biomarker or imaging phenotype or other noninvasive assessment.
Relief from congestion, a hallmark of AHF patients, will remain an important goal of therapy. Yet, past, current and future work will continue to explore other constructs, as the tendency to categorize therapies either as 'diuretics' or 'fluid removal', 'vasodilation' or 'inotropes' may lose its preeminence concurrent with improved pathophysiologic understanding. Two concepts – organ protection and neurohormonal antagonism – while not novel, but unique in its application to the acute setting, will continue to be explored.
The heart and the kidney are the most commonly discussed organs in regards to the organ protection hypothesis. Troponin release is associated with worse in-hospital outcomes in AHF, though its impact on longer term outcomes is less certain. Patients with baseline troponin release had similar adverse outcomes as those who had normal troponin levels at baseline, but subsequently increased during hospitalization, suggesting a potential window of opportunity where prevention of injury might affect outcomes. In the recent RELAX-AHF trial, differential effects were noted on the kidney and heart by cystatin C and high-sensitivity troponin with experimental (i.e., serelaxin) therapy Although a secondary endpoint, mortality at 180 days was also lower in the serelaxin arm, re-invigorating the hypothesis that prevention of organ injury might lead to improved outcomes. However, the exact mechanism by which troponin release occurs in AHF is not fully understood.
Neurohormonal antagonism is well established as a key target in HF patients with reduced systolic function. Whether or not neurohormonal blockade might be of benefit acutely has not been well studied. Mineralocorticoid receptor antagonism, for example, might be of benefit in AHF, though prospective studies are needed. Spironolactone is inexpensive, effective orally, and has both genomic and nongenomic effects, including diuresis at higher doses, that makes its potential role in AHF appealing.
Of note, these examples do not encompass all of the many different, unique and exciting lines of research being pursued. One notable example are biomarker-guided trials in AHF.
Patient centered or personalized medicine has become part of the lexicon of high-quality health care, with patient satisfaction included as part of financial reimbursement. In HF, patients are often discharged despite continuing to be symptomatic or without significant loss of body weight, both of which have been associated with higher rates of re-hospitalization. These data are in contrast to physician-reported outcomes, where the vast majority of patients have improvement in signs and symptoms, suggesting increased attention to patient-reported outcomes (PROs) may be of value. Although dyspnea is the most commonly reported symptom in AHF, there remains no validated PRO, although the use of simple Likert or Visual Analog Scale is now well established.
As Tinetti and colleagues highlight, multimorbidity is the most common chronic medical condition in older patients. HF represents a case in point, disproportionately afflicting older adults. For those with a preserved ejection fraction, at the present time, management of comorbidities has been suggested as the cornerstone of care given the lack of evidence-based HF therapies for a group that makes up nearly 50% of all HF patients. Given the overall aging of the U.S. population, further research and subsequent clinical evidence to help guide the management of multimorbidity, especially in older patients is an active area of current research and will continue These patients present a particular challenge to emergency physicians, who have no prior established relationship. A better understanding of the risk factors that are not necessarily biologic in nature but include important prognostic value, such as cognition, caregiver support, frailty, self-care and literacy, to name just a few, is needed.
Although the management of AHF generally involves administration of IV therapy, continued treatment with chronic oral medication is an area of evolving importance. Contrary to conventional thinking, continuation of β-blocker therapy is not associated with a deterioration of cardiac function in-hospital and increases the likelihood that patients will be discharged on such agents. Although it is not exactly clear when this should happen in the course of treatment, the most recent American Heart Association/American College of Cardiology (AHA/ACC) HF guidelines do recommend (Class I, level of evidence B) that guideline developed medical therapy (GDMT) be continued in the absence of hemodynamic instability or contraindications. Accordingly, for patients who respond well to initial IV treatment, it is not unreasonable to consider the addition of GDMT early in their course.
Expert Commentary & Five-year View
Recent history suggests a grim future regarding the early management of AHF. Current treatment today largely mirrors treatment from 40 years ago and outcomes remain persistently poor. Attempts to develop novel therapies for AHF have largely failed. As the population ages, combined with continual improvements in cardiovascular care, more patients will have HF and the subsequent financial costs will also increase. Although new knowledge has been learned over the last 10 years, persistent efforts are needed to improve outcomes. Several themes are worth highlighting related to the future of AHF in the ED.
The Role of the ED Regarding Quality Improvement & Research
More than any other factor, admission rates contribute the most toward re-admission rates. In other words, baseline admission rates are the greatest predictor of re-admission; yet at the present time, efforts focus more on preventing re-admissions than index admissions and are more specialty based, rather than interdisciplinary. Although the scientific value of 30-day re-admissions is debated, it is likely that cost containment or the more politically correct term of 'value' will continue. Thus, EDs will come under greater scrutiny with regards to admission/discharge decisions. Yet, this is a potential opportunity for EDs to engage more deeply in the continuum of care.
This need to better understand the ED phase of management also applies to research. AHF patients are heterogenous; yet, treatment is largely homogenous. Classification of patients to better target treatment is appealing and intuitive, yet requires further study to determine whether such an approach improves outcomes. Classification helps generate hypotheses, however, as grouping might direct further inquiry into the underlying pathophysiology of AHF. Initial and intriguing attempts using biomarkers have already begun; more work is needed.
Improved Phenotyping of Patients
In addition to biomarkers, advanced imaging techniques and noninvasive hemodynamics are opportunities to better understand the structure, function and hemodynamic state of patients. It is a presumption that characteristics observed during hospitalization were present in the ED to the same degree. Although this may be true for some patients, there may be other subgroups where unique characteristics are observed in the ED that change with treatment. Specifically, echocardiography would allow for greater characterization of patients at the time of presentation. Importantly, serial exams may demonstrate changes over time, highlighting opportunities where intervention might alter the pathophysiologic trajectory of some patients.
Characterization of patients could also happen in reverse, where detailed clinical phenotypes are recorded and biological specimens are collected in order to be further analyzed at the 'omic' level. In addition to improved pathophysiologic understanding, new therapeutic targets might be identified. Generating hypotheses from real-world clinical observation requires robust interdisciplinary collaboration.
Improved clinical phenotyping would also allow for more selective patient inclusion for clinical studies or even 'guided' studies, where only patients with specific characteristics are included. For example, differentiating treatment based on the presence or absence of a novel biomarker. Other possibilities include continuation, escalation or withdrawal of treatment guided by either a biomarker or imaging phenotype or other noninvasive assessment.
Moving Beyond Traditional Categories
Relief from congestion, a hallmark of AHF patients, will remain an important goal of therapy. Yet, past, current and future work will continue to explore other constructs, as the tendency to categorize therapies either as 'diuretics' or 'fluid removal', 'vasodilation' or 'inotropes' may lose its preeminence concurrent with improved pathophysiologic understanding. Two concepts – organ protection and neurohormonal antagonism – while not novel, but unique in its application to the acute setting, will continue to be explored.
The heart and the kidney are the most commonly discussed organs in regards to the organ protection hypothesis. Troponin release is associated with worse in-hospital outcomes in AHF, though its impact on longer term outcomes is less certain. Patients with baseline troponin release had similar adverse outcomes as those who had normal troponin levels at baseline, but subsequently increased during hospitalization, suggesting a potential window of opportunity where prevention of injury might affect outcomes. In the recent RELAX-AHF trial, differential effects were noted on the kidney and heart by cystatin C and high-sensitivity troponin with experimental (i.e., serelaxin) therapy Although a secondary endpoint, mortality at 180 days was also lower in the serelaxin arm, re-invigorating the hypothesis that prevention of organ injury might lead to improved outcomes. However, the exact mechanism by which troponin release occurs in AHF is not fully understood.
Neurohormonal antagonism is well established as a key target in HF patients with reduced systolic function. Whether or not neurohormonal blockade might be of benefit acutely has not been well studied. Mineralocorticoid receptor antagonism, for example, might be of benefit in AHF, though prospective studies are needed. Spironolactone is inexpensive, effective orally, and has both genomic and nongenomic effects, including diuresis at higher doses, that makes its potential role in AHF appealing.
Of note, these examples do not encompass all of the many different, unique and exciting lines of research being pursued. One notable example are biomarker-guided trials in AHF.
Patient-reported Outcomes
Patient centered or personalized medicine has become part of the lexicon of high-quality health care, with patient satisfaction included as part of financial reimbursement. In HF, patients are often discharged despite continuing to be symptomatic or without significant loss of body weight, both of which have been associated with higher rates of re-hospitalization. These data are in contrast to physician-reported outcomes, where the vast majority of patients have improvement in signs and symptoms, suggesting increased attention to patient-reported outcomes (PROs) may be of value. Although dyspnea is the most commonly reported symptom in AHF, there remains no validated PRO, although the use of simple Likert or Visual Analog Scale is now well established.
Management of Multimorbidity & Older Patients
As Tinetti and colleagues highlight, multimorbidity is the most common chronic medical condition in older patients. HF represents a case in point, disproportionately afflicting older adults. For those with a preserved ejection fraction, at the present time, management of comorbidities has been suggested as the cornerstone of care given the lack of evidence-based HF therapies for a group that makes up nearly 50% of all HF patients. Given the overall aging of the U.S. population, further research and subsequent clinical evidence to help guide the management of multimorbidity, especially in older patients is an active area of current research and will continue These patients present a particular challenge to emergency physicians, who have no prior established relationship. A better understanding of the risk factors that are not necessarily biologic in nature but include important prognostic value, such as cognition, caregiver support, frailty, self-care and literacy, to name just a few, is needed.
Other Considerations
Although the management of AHF generally involves administration of IV therapy, continued treatment with chronic oral medication is an area of evolving importance. Contrary to conventional thinking, continuation of β-blocker therapy is not associated with a deterioration of cardiac function in-hospital and increases the likelihood that patients will be discharged on such agents. Although it is not exactly clear when this should happen in the course of treatment, the most recent American Heart Association/American College of Cardiology (AHA/ACC) HF guidelines do recommend (Class I, level of evidence B) that guideline developed medical therapy (GDMT) be continued in the absence of hemodynamic instability or contraindications. Accordingly, for patients who respond well to initial IV treatment, it is not unreasonable to consider the addition of GDMT early in their course.
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