On April 19, 2023, an expert clinical decision pathway and scientific statement were published simultaneously in JACC. Both of these documents were aimed at providing an overview of heart failure with preserved ejection fraction, including diagnosis and management, based on contemporary evidence.
The American College of Cardiology is taking aim at improving the quality of care for people with heart failure with preserved ejection fraction (HFpEF) with a pair of new documents.
Simultaneously published in its flagship journal, the Journal of the American College of Cardiology, on April 19, 2023, the expert clinical decision pathway and scientific statement provide a comprehensive overview of evidence-based best practices for diagnosis and management of HFpEF.
A 25-page document citing more than 150 references, the scientific statement was penned with the intent of an in-depth and updated examination of the epidemiology, pathophysiology, diagnosis, and treatment of HFpEF. The statement is broken down into 6 main sections pertaining to epidemiology, clinical outcomes, pathophysiology, diagnosis, treatment, knowledge gaps, as well as a conclusion. Written by Barry Borlaug, MD, of the Mayo Clinic, Kavita Sharma, MD, of Johns Hopkins Medicine, Sanjiv Shah, MD, of Northwestern University, and Jennifer Ho, MD, of Massachusetts General Hospital, the document also contains 6 tables and 8 figures outlining key data on topics ranging from different diagnostic criteria to mechanisms of hemodynamic congestion.
A report from the ACC’s Solution Set Oversight Committee, the expert clinical decision pathway is the result of a collaborative effort led by Michelle Kittleson, MD, PhD, director of Heart Failure Research at Smidt Heart Institute at Cedars-Sinai, and a team of 7 colleagues. At 44 pages in length and citing 249 references, the document is broken down into 9 sections, with each section containing multiple subsections. As with other expert clinical decision pathways from the ACC, this document was published with the intent of informing the development of various tools that accelerate real-time use of clinical policy at the point of care.
Within the 44-page document are 6 tables and 15 figures, including 2 figures outlining acronyms designed to help guide different clinicians through the diagnosis and care of this patient population: CHECK-IN and INHALE.
Collaboration: Need for specialist care to manage comorbidities.
High-risk features: Heart failure hospitalizations, pulmonary hypertension RV dysfunction.
Extensive evaluation needed
Knowledge of HFpEF mimics: Valvular disease, HCM, amyloid pericardial disease
Increased need for diuretic agents
NYHA Class III of IV Symptoms
In need of diagnosis
Nonresponsive to diuretic agents; Natriuretic peptides extremely high
Hospitalize frequently for heart failure
Acute or chronic end-organ dysfunction
Low blood pressure
Evidence of HFpEF mimics
With an interest in learning more about the documents and how they help address the unmet need within HFpEF, HCPLive reached out to Kittleson for further perspective. That conversation is the subject of the following Q&A.
HCPLive: Can you provide some perspective on the current levels of unmet need in HFpEF and what factors drive the difficulty in the management and diagnosis?
Kittleson: I think the thing that makes HFpEF so challenging is 2-fold. Number 1, diagnosis is tricky. Number 2, because diagnosis is tricky, it's very under-recognized. So, all any clinician really wants is a test to give you an answer. With HFrEF, it's easy in the sense that you have an echocardiogram and, if it shows you a low EF, all of a sudden you can be thrown down the appropriate diagnostic and treatment pathway.
HFpEF is so much more challenging because there is no sine qua non, there's no gold standard. You have a patient with dyspnea and edema, but they can present in so many different ways. They may present to their internist, they may present to a cardiologist, they may present to a pulmonologist. There are so many different avenues by which these patients are funneled into the medical system.
So, the first goal of this expert clinical decision pathway was to say, "Can we help clinicians to better make the diagnosis?" and that starts, like most things in medicine, by going back to basics and understanding the differential diagnosis of dyspnea and edema. We cover that and we talk about the fact that there are diagnostic scoring algorithms that can be very useful, but they're not perfect. The most important triage, I think, when it comes to the diagnosis is to look through Figure 8, because Figure 8 tells you the steps.
For example, in infiltrative cardiomyopathy, don't forget about amyloidosis, which 15% of patients in 1 series diagnosed with HFpEF truly have. There's also hypertrophic cardiomyopathy, pericardial disease, valvular disease, high output heart failure. We have to consider the history and physical in the echo, which are extraordinarily helpful in teasing this out.
If, and only if, you've convinced yourself that 1 of these diagnoses for a disease with directed therapy does not exist. Then you can say the patient has HFpEF, but the story doesn't end there. Then you move on to what's the best therapy.
We divide therapy into 2 important categories, which are comorbidities and guideline-directed medical therapy. Comorbidities are hugely important because there's a complex interplay in patients with HFpEF between the comorbidities and their functional capacity and outcomes, such as atrial fibrillation, coronary artery disease, obesity, kidney dysfunction, hypertension, and sleep apnea. These all contribute to the genesis of HFpEF and also can worsen the outcomes of patients with HFpEF. So, optimizing the comorbidities, which will involve multi-disciplinary collaboration as well as thinking about guideline-directed medical therapy.
HCPLive: Outside of Figure 8, are there any other figures or tables you would specifically highlight when discussing key points from the document?
Again, I love Figure 8 because I think it encapsulates the importance of thinking about not just the heart, but the patient. Next, Figure 9, I think, beautifully encapsulates the guideline-directed medical therapy and what we truly try to emphasize here is the importance of the SGLT2 inhibitor. How wonderful to finally have a randomized control trial in HFpEF that meets its primary endpoint with a reduction in the combined endpoint of cardiovascular death and heart failure hospitalizations. Now, we have 2 trials, with EMPEROR-Preserved and DELIVER. That is hugely important.
It also addresses considering, in other groups, when do you need a loop diuretic? When should you consider the MRA or ARNI? So, I think when you're thinking about guideline-directed therapy, you will find Figure 9 very high yield.
Finally, unlike HFrEF, which seems in many ways uniquely a cardiac condition, HFpEF is quite a systemic condition with contributing and exacerbating precipitating comorbidities. For that Figure 11, really summarizes the comorbidities that require specific attention. This includes AFib, hypertension, CAD, diabetes, CKD, sleep apnea, and obesity.
So, if I were a busy clinician flipping through a document, I would say, put your attention on those 3 figures. Often, my guidance for clinicians is: Don't read the document from start to finish. Use the all-important search function, especially if you have a specific patient-related question–use that search function go to the part of the document that's most relevant for you at that moment.
HCPLive: Among the biggest heart failure news from 2022 were the results of STRONG-HF, which is mentioned throughout the expert clinical decision pathway. How important was having this trial when formulating this document?
Kittleson: I think STRONG-HF is so important for clinicians because we have always said you should optimize GDMT and you should titrate to maximal doses. It wasn't until STRONG-HF came out that we had a randomized trial to tell us that, in fact, doing that can help your patients feel better, stay out of the hospital, and live longer.
I think what STRONG-HF has told us is that the theory we all believed in, is now proven in practice and the beauty of the STRONG-HF trial is that it enrolled patients with HFrEF and HFpEF. It's quite incredible. And, as has been noted, SGLT2 inhibitors were not included because the trial predated the benefit of those. So, can you imagine how much better the benefit would have been observed if they would have used SGLT2 inhibitors for their HFrEF and HFpEF patients?
HCPLive: Can you talk about some of the nuances of GDMT for HFpEF relative to GDMT for HFrEF?
Kittleson: So, I think the 4 pillars for HFrEF have been very clearly emphasized in the guidelines, which are fully directed by the evidence from the clinical trial. When it comes to someone with HFrEF, they should be on an ARNI, beta-blocker, MRA, and SGLT2 inhibitor. It will help your patients feel better stay out of the hospital live longer, potentially improve heart function.
For patients with HFpEF it's more subtle. I think the figure on GDMT reflects that. We know, now, based on EMPEROR-Preserved and DELIVER that SGLT2 inhibitors are absolutely the best we can offer our HFpEF patients and as soon as you have appropriately diagnosed has HFpEF, give those patients and SGLT2 inhibitor. The other pillars are more subtle.
If you went truly by the guidelines, they tell you a loop diuretic is absolutely indicated for symptomatic relief and others have a relatively weaker class 2b indication: the MRA, ARNI, and the ARB. So, when it comes to a class 2b indication—under which the MRA, ARNI, and ARB all fall—because of the clinical trial data, with none of those trials meeting their primary endpoint, we're relying on subgroup analysis to give us hypothesis-generating suggestions of benefit and it comes down to judgment and experience.
So, I think when you think about HFpEF, it's a little different. If you want me to put into 4 pillars, I would say the first pillar is make sure you have the right diagnosis. The second pillar is manage your comorbidities. The third pillar is an SGLT2 inhibitor. The fourth pillar is look closely at the subgroup analyses of the MRA, ARNI, ARB and see if they match your patient for whom they may derive benefit.
HCPLive: Can you explain the CHECK-IN acronym and why you emphasize the role of primary care as such an important theme in the expert clinical decision pathway?
Kittleson: Hats off to primary care physicians. They are the superheroes who have to, better than any of us, understand the art of diagnosis and the art of knowing when your patient is sick. When it comes to a patient with HFpEF, they will not be easily slotted into a cardiologist because the echocardiogram might look quote unquote "Okay", but you have a patient with dyspnea and edema. So, knowing when such a patient needs to check in with a cardiologist is difficult.
The CHECK-IN mnemonic focuses on when a primary care specialist may be unsure of the diagnosis or concerned about the trajectory of disease. So, if you're unsure of the diagnosis or you're concerned about the trajectory, whether of their cardiac disease or their comorbidities then it's time to get help.
Medicine is a team sport; we work with multidisciplinary collaboration. Recognizing that these patients may never get to cardiologists, giving guidance to those primary care clinicians on when you should ask for the more guidance in the management is important.
HCPLive: The second acronym in the document is INHALE. Unlike CHECK-IN, this is focused towards cardiologists. Why was it important to include this?
Kittleson: I have great respect for the cardiologist who feels they can manage their patients appropriately. I also have great respect for cardiologists who feel that they instinctively know when to refer their patients to higher levels of care.
I like to say that every disease has a rhythm and a trajectory. The longer you've been in clinical practice, the more you get comfortable with the expected rhythm and trajectory of various medical conditions. With that experience, you know when patients are falling outside the norm and when you need to ask for help. However, not everyone is an experienced clinician. So, I would be very happy if the experienced clinicians in the room say "Cute, but I don't need it". But for those who are still learning, still gaining their experience, it's lovely to have guidance.
The INHALE mnemonic follows a similar pattern when you're either not sure of the diagnosis or, if despite your management, patients are doing worse. It is time to reach out for more help in how these patients should be managed. So, it is akin to the absolutely outstanding "I NEED HELP" mnemonic that Dr. Baumwol from Australia put together at ISHLT 2017. This is a similar idea of how that applies to patients with HFpEF.
HCPLive: Are there any other key points surrounding the document you think are important to note?
Kittleson: I actually want to point out these 2 statements were planned and created in parallel. This was the sort of the brainchild of Dr. [Valentin] Fuster, the Editor in Chief of JACC, to highlight the importance with 2 complementary, but not redundant statements.
So, if you look at the pair together, you will see that the scientific statement delves much deeper into things like epidemiology, pathophysiology, and future advances. That is by design. Ours is meant to be a handbook for clinicians when their patient is sitting in front of them and the scientific statement is meant to be a deeper dive into those issues to provide greater insight into this beautiful condition of heart failure with preserved ejection fraction. I think that's very important to include when we're putting these statements in context.
Editor's note: This transcript has been edited for length and clarity.