The latest update to U.S. guidelines for heart failure management, released at the end of April , puts unprecedented emphasis on heart failure prevention and also shines a brighter light on patients at risk for developing heart failure – people with hypertension, diabetes, or coronary artery disease.
“We have embraced the fact that heart failure can be prevented and that the progression of heart failure can be interrupted, and we articulated how we can use biomarkers to screen patients with asymptomatic left ventricular dysfunction,” said Clyde W. Yancy, MD, chair of the writing group that issued the 2017 focused update to the heart failure management guidelines on behalf of the American College of Cardiology, the American Heart Association, and the Heart Failure Society of America. (Circulation. 2017 Apr 28. doi: 10.1161/CIR.0000000000000509).Mariell Jessup, MD, chief scientific officer for the Leducq organization in Boston.
This means that, for the first time, these guidelines focus on stage A heart failure patients, those without symptoms or detectable left ventricular dysfunction but at risk for heart failure, a heart failure subgroup that was ignored in the past. Prevention is most immediate for stage A patients. The new guidelines cite the stage A definition from the 2009 guidelines: patients with “risk factors that clearly predispose toward the development of heart failure. For example, patients with coronary artery disease, hypertension, or diabetes mellitus who do not yet demonstrate impaired left ventricular function.”
The number of patients with coronary artery disease, hypertension, or diabetes is pretty large. The new heart failure guidelines apply to many people.
“The mindset [on heart failure] has been on treatment, not prevention. There is far more focus [in the new guidelines] on prevention than ever before,” commented Javed Butler, MD, professor and chief of cardiology at Stony Brook (N.Y.) University and a member of the guideline writing panel.
“One reason why heart failure prevention has not been a focus was because people thought that, if you prevented coronary artery disease, you prevented heart failure. What we’ve learned is that a lot of heart failure is not ischemic and not from overt coronary disease, especially age-related HFpEF [heart failure with preserved ejection fraction]. Hopefully, these guidelines will spur more interest in prevention and risk factor control,” Dr. Butler said in an interview.
It starts with blood pressure
The guidelines contain an entirely new section devoted to blood pressure, and, while part of the section deals with a target blood pressure for symptomatic (stage C) heart failure patients (a goal systolic pressure of less than 130 mm Hg for patients with either a preserved or reduced ejection fraction), the first entry is a target blood pressure of less than 130/80 mm Hg for all stage A heart failure patients.
Because stage A is defined to include any adult with hypertension, the new heart failure guidelines set a new blood pressure treatment goal for all U.S. adults with hypertension at a time when the long-awaited revision to U.S. hypertension management guidelines from the ACC and AHA are still pending. Until the new hypertension guidelines come out – they’re expected later this year – the blood pressure target set in the heart failure guidelines will have to suffice.
Indeed, the less than 130/80-mm Hg target for on-treatment blood pressure set for heart failure prevention in the new guidelines was picked to “harmonize” with the guidelines that the ACC and AHA hypertension panel will soon release, Dr. Jessup said in an interview.
The main evidence for this target, lower than in most prior U.S. hypertension guidelines, comes from SPRINT (Systolic Blood Pressure Intervention Trial) (N Engl J Med. 2015 Nov 26;373:2103-16). In that trial, the goal blood pressure that linked with the best outcomes was less than 120/80 mm Hg, although the average achieved systolic blood pressure was above that goal with a mean systolic pressure of 121.5 mm Hg. One reason for setting a higher goal systolic pressure for practice was that analyses have shown that blood pressure measurement in SPRINT did not perform like conventional measurements in routine practice. SPRINT patients appeared to have lower measured pressures than they would have recorded had they been measured by more conventional means (Hypertension. 2017 January;69:15-9).
“The way that blood pressures were measured in SPRINT, a pressure of 120/80 mm Hg in the trial was akin to a pressure of 130/80 mm Hg in an office,” Dr. Yancy, chief of cardiology at Northwestern University, Chicago, said in an interview. “To avoid dangerous hypotension and to approximate SPRINT, an office pressure of less than 130 mm Hg is a reasonable number.”
New role for BNP screening
Stage A patients are more than just the target for more aggressive hypertension control. They are now also potential candidates for screening for an elevated blood level of brain natriuretic peptide (BNP) or N-terminal (NT)–proBNP. The guidelines panel makes this a level IIa recommendation, saying that a screening BNP test in patients at risk for developing heart failure can be useful if followed by team-based care and optimized guideline directed medical therapy.
This guideline follows the lead of two successful controlled trials that focused more aggressive preventive treatments on stage A patients with an elevated level of BNP or NT-proBNP – the STOP-HF (JAMA. 2013 July 3;310:66-74) and PONTIAC (J Am Coll Cardiol. 2013 Oct;62:1365-72) trials. The target population for some type of BNP screening are patients with cardiovascular disease, vascular disease, diabetes, obesity, or hypertension, Dr. Yancy said. “It was evident in STOP-HF that, if you screened and intervened, you could make a difference” in the development of heart failure.
The STOP-HF intervention included “optimal risk factor management” and “coaching by a specialist nurse who emphasized individual risk status and the importance of adherence to medication and healthy lifestyle behaviors.”
The guidelines aren’t clear on which patients at risk for developing heart failure, stage A patients, should get screened with BNP or NT-proBNP. Dr. Jessup said that it’s for patients in whom a positive result would trigger more aggressive management.James L. Januzzi, MD, professor of medicine at Harvard Medical School and a heart failure cardiologist at Massachusetts General Hospital, both in Boston. He said that both BNP and NT-proBNP are equally good options for screening at-risk patients as markers of incident heart failure. Positive levels flagging left ventricular involvement would be a BNP of at least 50 pg/mL or an NT-pro-BNP of at least 125 pg/mL. Patients with levels like these need echocardiographic assessment, as well as optimization of blood pressure control, optimization of statin treatment, optimization of all their other medications, and, if the patient has diabetes, assessment for possible silent ischemia, said Dr. Januzzi.
Getting a BNP on a suspect patient can raise a red flag to the patient, as well as to the physician, that more intervention is needed. “It’s easy for a physician to ignore a high-risk patient who looks okay and feels okay.” A BNP or NT-proBNP test can pick out the patients who shouldn’t be ignored, Dr. Januzzi said.
HFpEF treatment now possible
Another groundbreaking change in the guidelines is inclusion, for the first time, of a medical treatment specific for HFpEF. The aldosterone receptor antagonists (ARAs) spironolactone and eplerenone received a class IIb recommendation: An ARA might be considered to decrease hospitalizations in patients with HFpEF with an ejection fraction of at least 45%, an elevated BNP or recent hospitalization, and good renal function and potassium level.
The “might be considered” recommendation is guarded but understandable given that the evidence comes from the somewhat controversial, post-hoc analysis of data from the pivotal TOPCAT trial (N Engl J Med. 2014 Apr 10;370:1383-92) that focused on just the roughly half of patients seen at centers in North or South America (Circulation. 2015 Jan 6;131:34-42).
“It would be irresponsible to overlook the potential that [ARAs] may help patients who looks like the ones enrolled in TOPCAT in the Americas,” said Dr. Yancy. “We blended evidence and pragmatism and said that the field needs this” treatment. He said that an ARA was a reasonable option for HFpEF patients with symptoms of heart failure and a positive biomarker test result.
Dr. Butler largely agreed. ARA treatment is for HFpEF patients with symptomatic heart failure and either a history of hospitalization or a high BNP level, he said.
“I was surprised by how strongly the committee felt there was a reasonable signal of help from ARAs in HFpEF,” said Dr. Jessup. “I believe in them too,” she added.
Dr. Jessup suggested targeting an ARA to a HFpEF patient with some hypertension, some volume problem, some peripheral edema, and a lot of breathlessness but with no underlying ischemia. “I use an ARA on these patients pretty quickly,” Dr. Jessup said. It’s best to start with a low dosage and see how the patient responds. “The best responders have a really stiff heart” and are usually not the more elderly HFpEF patients. ARA treatment also provides more steady volume control, superior to furosemide, she said.
Yet more additions
The revised guidelines contain even more changes. “We say that checking for anemia is important and how iron is an intervention that might make a difference,” said Dr. Jessup. Also, primary care physicians and cardiologists “should look for obstructive sleep apnea” in heart failure patients for whom “intervention with weight loss might help,” she said.
Another feature is the focus on tailored treatment, with many treatment elements that need customizing to each different type of heart failure patient. “Not every drug needs to be given to every patient,” Dr. Yancy warned.
The specifics of how to orchestrate all the guidelines into a coherent management plan may become clearer later this year, when the ACC/AHA group will release a follow-up “Heart Failure Pathways” document, aimed at bridging the gap between guidelines and actual clinical practice, Dr. Yancy said. “We want more value from writing the guidelines. The biggest obstacle is how to implement them,” and that’s what the pathways follow-up will address.
“The biggest challenge the societies have is how to motivate physicians and nurses to more aggressively treat heart failure,” said Dr. Butler.
Dr. Yancy and Dr. Jessup had no disclosures. Dr. Butler has been a consultant to 11 companies. Dr. Januzzi has been a consultant to Critical Diagnostics, Novartis, Phillips, Roche Diagnostics, and Sphingotec, and he has received research support from Amgen, Boehringer Ingelheim, Janssen, and Prevencio.
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