AHA/ACC guidelines on heart failure treatment

 The American Heart Association, American College of Cardiology, and the Heart Failure Society of America recently published an update of the 2013 multisociety guideline as well as the more recent 2017 update. For the full 159-page document, see https://reader.elsevier.com/reader/sd/pii/S0735109721083959?token=CB9580AA49BDFBDED37DEAE7D70EE6A62D8C458BE5FB7885772CC1A1152D557D66CEEB34771305D43089105C9545D082&originRegion=us-east-1&originCreation=20220521232432 ; for the 24-page executive summary, see  heart failure guidelines AHA etc JACC2022 in dropbox, or https://doi.org/10.1016/j.jacc.2021.12.011)​

Review of guidelines:

-- stages of heart failure (HF), revised:

    -- stage A: HF prevention: asymptomatic, modify risk factors (hypertension, atherosclerotic disease, diabetes, metabolic syndrome, obesity)

    -- stage B: asymptomatic, but evidence of reduced left or right ventricular systolic function, ventricular hypertrophy, chamber enlargement, wall motion abnormalities, valvular heart disease (evidence includes noninvasive imaging such as BNPs, or persistently elevated cardiac troponin

    -- stage C: symptomatic, structural heart disease with current or previous symptoms of heart failure

    -- stage D: advanced HF, symptoms that interfere with daily life and with recurrent hospitalizations despite attempts to optimize GDMT (guideline-directed medical therapy)

--Definitions of HF with reduced and preserved ejection fractions are not consistent in the literature. This guideline considers HFrEF (HF with reduced ejection fraction) as ejection fraction (EF)≤40%; and HFpEF (HF with preserved ejection fraction) as >50%. And the EF 41-49% being in the middle HFmEF (HF with mildly reduced EF, with some studies have suggested that those with EF 41-45% behave as HFrEF And those with EF 46-49% as HFpEF, not so surprisingly, see http://gmodestmedblogs.blogspot.com/2017/11/heart-failure-with-mid-range-ejection.html)

10 "take-home messages":

--  HFrEF treatment: GDMT ( guideline-directed medical therapy) for now includes four classes of medication: angiotensin receptor-neprilysin inhibitors (ARNi); ACE inhibitors or ARBs, beta blockers, mineralocorticoid receptor antagonists (MRAs), and SGLT-2 inhibitors

    -- If stable and NYHA class II to III symptoms, an ARNi  Is recommended to reduce morbidity and mortality, Class A recommendation, LOE (Level of evidence) A

    -- patients with previous or current symptoms of chronic HF, ACE is beneficial to reduce morbidity and mortality, when an ARNi is not feasible, Class A/LOE A

    -- patients with previous or current symptoms of chronic HF who are intolerant of an ACE because of cough or angioedema and ARNi is not feasible, use ARB to reduce morbidity and mortality, Class A/LOE A

    -- patients with chronic symptomatic class II or III HF who tolerate an ACE or ARB, replacement by an ARNi is recommended to reduce morbidity and mortality, Class A/LOE B

   -- in patients with current or prior symptoms of HF use 1 of 3 beta blockers (bisoprolol, carvedilol, sustained-release metoprolol succinate) to reduce mortality and morbidity, Class A/LOE A

    -- patients with class II to IV NYHA symptoms, MRA (spironolactone or eplerenone) is recommended to reduce morbidity and mortality, only if eGFR>30 and serum potassium <5. Carefully monitor renal function, potassium, and diuretic dosing

    -- patients with chronic symptomatic HF, SGLT-2 inhibitors are recommended to reduce hospitalization and cardiovascular mortality, irrespective of the presence of diabetes, Class A/LOE A

-- HFpEF treatment: 

    -- SGLT-2 Inhibitors can be beneficial in decreasing hospitalizations and cardiovascular mortality, Class 2a/LOE B

    -- MRAs may be considered to decrease hospitalization particularly among patients with LVEF on the lower end of the spectrum, Class 2b/LOE B

    -- ARNi may be considered to decrease hospitalizations particularly in those with LVEF on the lower end of the spectrum, Class 2b/LOE B

    -- management of atrial fibrillation, including ablation, may improve symptoms, Class 2a/LOE C

    -- consider ARB to decrease hospitalizations, especially with those with ejection fractions on the lower end of the spectrum, Class 2b/LOE B

-- HRmEF (this is the group with mildly reduced EF, in the 41-49% range)

    -- SGLT-2 inhibitors can be beneficial, Class 2a/LOE B

    -- Can consider the treatments for HFrEF above, especially those in the lower end of this EF range, Class 2b/LOE B

-- treatment-related improvement in heart failure: GDMT Should be continued to prevent relapse of HF and left ventricular dysfunction, even if patients are asymptomatic

-- primary prevention of heart failure:

    -- stage A:

        -- controlling hypertension, Class A/LOE A

        -- diabetes: use of SGLT-2 inhibitors to prevent hospitalizations for HF, Class A/LOE A

        -- general population: regular physical activity, maintaining normal body weight, healthy dietary patterns, and avoiding smoking, Class A/LOE B

        -- for patients at high risk of developing HF: BNP-based screening, followed by team-based care, Class 2a/LOE B

        -- general population: validated multivariable risk scores can be useful to estimate subsequent risk of HF (e.g., see https://www.ahajournals.org/doi/10.1161/circheartfailure.111.964841 , which basically adds N-terminal BNP to traditional cardiovascular risk scores)

    -- stage B (also asymptomatic):

        -- if LVEF <40%, use ACE inhibitors, Class A/LOE A

        -- in those who had recent MI and LVEF <40% but are intolerant of ACE inhibitors, use ARBs, Class A/LOE B

        -- in those at least 40 days post-MI with LVEF <30% and NYHA class I symptoms (asymptomatic) while on GDMT, consider an implantable cardioverter-defibrillator if life expectancy is at least one year, to prevent sudden cardiac death/reduce total mortality, Class A/LOE B

        -- if LVEF <40%, use beta blockers to prevent symptomatic heart failure, Class A/LOE C

        -- if LVEF <50%,do not use thiazolidinediones or nondihydropyridiine calcium channel blockers because of increased risk of heart failure

-- management of comorbidities:

    -- iron deficiency: reasonable to treat even without anemia to improve functional status and quality of life, Class 2a/LOE B (also, use of erythropoietin agent should not be used to improve morbidity and mortality, Class 3/LOE B, ie, harm)

    -- sleep disorders: in patients with sleep disordered breathing, formal assessment, and use of CPAP as needed, Class 2a/LOE B-C

    -- treatment for diabetes and hypertension as above

    -- atrial fibrillation: anticoagulate, DOAC preferred, Class 1/LOE A

        -- ablation is reasonable to improve symptoms and quality of life, Class 2a/LOE B

        -- AV nodal ablation if LVEF<50%, rhythm control not work, and high ventricular rate despite medical therapy, Class 2a/LOE B

    -- coronary artery disease: if EF<35% and suitable coronary anatomy, surgical revascularization plus GDMT is beneficial to improve symptoms, cardiovascular hospitalizations, and long-term all cause mortality, Class 1/LOE B

-- i did not include a few of their key points: one on relative cost of medications (all were basically <$60K per year except tafamidis for cardiac amyloid, and two devices); another on workup and treatment for cardiac amyloidosis (which has changed a lot); and comments on patients with ongoing cancer including potentially cardiotoxic chemotherapy

Commentary:

-- Heart failure is a growing problem in the United States, associated with our aging population. For example, total deaths from HF have increased from 275,000 in 2009 to 310,000 in 2014. There is also been an increase in HF hospitalizations. These changes have been associated with an increasing incidence of HFpEF, with decreases of HFrEF 

-- there have been some small differences in racial and ethnic groups, for example non-Hispanic black patients have an age-adjusted mortality rate of HF of 92/100Kvs non-Hispanic white patients at 87/100K, likely related to general disparities in social conditions leading to increased risk factors (e.g. hypertension) and decreased access to care

-- the American Heart Association, the largest and wealthiest of specialty organizations, does have the most rigorous policies in guideline development to minimize bias or improper influence. My review of the committee members found that the chair had no conflicts of interest reported, the vice chair had many, and of the total of 39 people on the committee 21 had no connections to industry reported (which, in the scheme of things, is pretty good). This is not to say that there aren't potential conflicts of interest anyway, since it might well be that the scientific leaders of an organization (who for the past several decades have been funded largely by industry) may well have inordinate sway over the other committee members, given their scientific prominence

-- this guideline has some significant changes: it elevates ARNIs to top position in many cases, SGLT-2's are repeatedly endorsed, and the guidelines focus on HF prevention/early detection and treatment

    -- ARNi's In the PARADIGM-HF study decrease all-cause mortality as well as cardiovascular mortality and hospitalizations for HF, as compared to full doses of ACE inhibitors: the death rate decreased 16%, death from cardiovascular causes by 20%, and risk hospitalizations by 21%, as well as improvement in quality of life in the physical and social domains

    -- I will send out a review on outpatient initiation of ARNis in a blog soon. This will also comment further on the PARADIGM-HF studies

-- I must admit that I am a little surprised at how SGLT-2 inhibitors have been elevated to such a prime position. The data are quite clear that they do decrease heart failure hospitalizations. However, they are basically loop diuretics but with their own quite serious complications:

    -- as noted in http://gmodestmedblogs.blogspot.com/2020/02/diabetes-glp1-agonists-vs-sglt2.html : adverse reactions are many, though several of them are infrequent, but include: lower extremity amputations, increased fracture risk (diabetics already have an increased risk of osteoporosis), diabetic ketoacidosis (even at very low blood sugar levels, eg  <200 mg/dL), severe mycotic infections, increased UTIs (and severe, ICU-bound cases of urosepsis), Fournier's gangrene. there are an array of FDA alerts about these problems: see http://gmodestmedblogs.blogspot.com/2019/06/diabetes-guideline-update-pushing-sglt.html

    -- though never formally tested in a randomized controlled trial, It is abundantly clear that the good old loop diuretics (eg furosemide, torsemide) do prevent heart failure exacerbations, hospitalizations, and mortality (if they were compared to a placebo control). and for patients with HFrEF and HFpEF

    -- and, these old loop diuretics have decades of experience, their adverse effects are abundantly known, and unlike SGLT2's they are titratable to the degree of heart failure. so it bewilders me a bit to elevate SGLT-2 inhibitors to the extent done in these guidelines

    -- The cardiovascular benefits of SGLT-2 inhibitors is basically in the arena of heart failure and not atherosclerotic cardiovascular disease (as opposed to GLP-1 receptor agonists, with documented benefit for CAD), so the range of cardiovascular benefits are limited: see https://pubmed.ncbi.nlm.nih.gov/30875065/

    -- there have been no trials comparing loop diuretics to SGLT-2 inhibitors in those with HF (all of those with HF and put on SGLT-2's are also on loop diuretics)

        -- maybe loop diuretics, with appropriate titration, would work as well or even better than SGLT-2's in preventing hospitalizations for HF??

        -- and, maybe, for that strong HF risk factor of hypertension, we should be using loop diuretics instead of thiazide-type diuretics, perhaps combos of losartan/torsemide instead of losartan/hydrochlorothiazide??

            -- loop diuretics are NOT recommended in current hypertension guidelines "largely due to the lack of outcome data" (per https://pubmed.ncbi.nlm.nih.gov/26951244/#:~:text=Loop%20diuretics%20are%20not%20recommended,and%20once%20daily%20dosing%20 )

        -- maybe, in this rush to SGLT-2's with their known and potentially future but currently unknown adverse effects, we should look more strongly into our tried-and-true old loop diuretics more seriously!!!!!

also, best to avoid NSAIDs, which can lead to increased heart failure, though it seems that aggressive sodium restriction is not helpful (see http://gmodestmedblogs.blogspot.com/2022/05/heart-failure-aggressive-sodium.html )

so, an important update to the guidelines, with, I think, an appropriate focus on ARNIs for therapy, given their pretty dramatic effects on cardiovascular morbidity and mortality. And, a strong emphasis on heart failure prevention and nonpharmacologic therapies. Though the studies are strong and consistent in the benefit of SGLT-2 inhibitors (and with the current state of knowledge, their use is reasonable), but perhaps we should look more into the known benefit of our old loop diuretics, as above.....

geoff

 

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