Systolic and Diastolic Heart Failure

Educational Objectives

The goal of this program is to improve the management of systolic and diastolic heart failure. After hearing and assimilating this program, the clinician will be better able to:

1. Select appropriate pharmacologic agents for management of systolic and diastolic heart failure.
2. Choose among standard therapies for heart failure based on the New York Heart Association Functional Classification system.
3. Manage comorbidities, such as iron deficiency and diabetes, in heart failure.

Summary

Heart failure with reduced ejection fraction (HRrEF): systolic heart failure (HF); echocardiography (echo) — the test of choice (simple, versatile, provides a decent volume of information; no associated radiation; relatively inexpensive); some prefer magnetic resonance imaging (MRI; provides relevant patterns for diagnosis, which may change treatment); echo does not provide similar patterns and is generally a visual estimate; strain echo provides a more quantitative measure of cardiac function (worse heart function with negative number below threshold)

Pharmacologic management: diuretic agents — furosemide, bumetanide, and torsemide are commonly used; furosemide has lower bioavailability than bumetanide or torsemide in decompensated HF; open-label study (Europe) — torsemide was associated with better results in endpoints of mortality, eg, cardiac, sudden-death, nonsudden death, and noncardiac mortalities; torsemide is a longer-acting drug; diuretic resistance — nonsteroidal anti-inflammatory drugs (NSAIDs) block natriuretic peptides (NPs) in the kidney; discontinue NSAIDs when possible; loop diuretics — cause distal tubule hypertrophy and more avid sodium uptake, resulting in less diuretic effect; resolve with addition of a thiazide diuretic (eg, metolazone)

Standard therapies for HF (New York Heart Association [NYHA] Functional Classification)

Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-2 receptor blockers (ARBs): data suggest more improvement in morbidity and mortality with ACE inhibitors than with ARBs; should not be used simultaneously because of risk for hypotension; initial dose of lisinopril is 2.5 to 5.0 mg with a goal of 20 to 40 mg/day (mean dose in clinical trials is 32.5 mg/day; most patients with HF do not receive doses that high)

β-blockers: can improve mortality; carvedilol, metoprolol succinate, and bisoprolol are associated with ≈30% reduction in mortality; metoprolol succinate and carvedilol are approved for use in the United States (US); one trial showed better results with carvedilol than with metoprolol tartrate, however, metoprolol succinate did not exist at the time (ie, metoprolol is not necessarily inferior to carvedilol); carvedilol is effective at lower doses, possibly more so than metoprolol; metoprolol succinate is once-daily dosing; goal dose is 25 mg twice daily for carvedilol, and 200 mg/day for metoprolol succinate; most of the speaker’s patients have not achieved such high doses; carvedilol has a greater effect on blood pressure (BP) than metoprolol succinate (may facilitate up-titration of other medications); carvedilol is insulin- and lipid-neutral; metoprolol succinate causes less bronchospasm

Nitric oxide (NO)-enhancing therapy: a fixed dose of isosorbide dinitrate plus hydralazine; the African-American HF Trial showed reduction in all-cause mortality

Aldosterone antagonists: eg, spironolactone and eplerenone; indicated for HF with reduced ejection fraction (HFrEF) <40% (NYHA class II-IV); generally recommended for use in women with creatinine <2 mg/dL, and men with <2.5 mg/dL; do not initiate if potassium levels are >5 mEq/L, especially in patients with diabetes mellitus; in a study comparing sacubitril/valsartan (Entresto) with enalapril 10 mg twice daily for HFrEF <40% (class II-IV), the primary endpoints of cardiovascular (CV) death and hospitalization for HF was reduced by ≈20%; preferred in the US; effective but expensive; ivabradine — affects the sinoatrial node (“funny channel”), leading to slow heart rate (HR); no effect on atrioventricular node or BP; studied in patients with class II to III HF, normal sinus rhythm, and HR >70 bpm despite maximum dose of β-blocker (European Society of Cardiology IIb recommendation)

Sodium-glucose cotransporter-2 (SGLT2) inhibitors: blockade of SGLT2 results in increased excretion of glucose; EMPA-REG OUTCOME trial — included diabetic patients with atherosclerotic cardiovascular disease (ASCVD); significant difference in major endpoints of CV mortality, stroke, and myocardial infarction (MI); genital infection was higher with empagliflozin than with placebo (6% vs 2%); EMPEROR-Reduced study — mean age was 67 yr, left ventricular (LV) EF ≈27%, N-terminal pro hormone B-type NP ≈1900 pg/mL; all patients (≈50% of whom had diabetes) were on guideline-directed medical therapy (GDMT); significant reductions in primary endpoints (CV death, hospitalization for HF) and secondary endpoint (first or recurrent HF hospitalization) were seen with empagliflozin; type II diabetes, with CVD and glomerular filtration rate ≥45 — empagliflozin, canagliflozin, and dapagliflozin are equally efficacious (exercise caution in patients taking insulin plus other agents); HFrEF without diabetes — empagliflozin and canagliflozin have been studied extensively, but insurance companies claim there is lack of indication (no diabetes)

Guanylate cyclase stimulator (GCS): generation of cyclic guanosine monophosphate and NO leads to relaxation of blood vessels and vasodilation; Victoria trial — showed a 10% reduction in death or hospitalization with GCS in those with HF class II to IV and one HF hospitalization

Comorbidities with HF: diabetes, chronic kidney disease (excluded in most trials), and atrial fibrillation (AF); iron deficiency (ID) — seen with stable HF; associated with decreased functional capacity, poor quality of life, and increased mortality; considered a therapeutic target in HF; consensus recommendation from ESC — for symptomatic HFrEF class II to III, with hemoglobin <15 g/dL, ferratin <100 μg/L, and transferrin saturation <20%, consider intravenous (IV) iron treatment

Device therapy: an infarct can lead to expansion, which causes slippage of myocytes in myocardium, and leads to aneurysmal formation and/or ventricular dilation; alteration of remodelling can minimize expansion; synchronize left and right ventricles (RV) by placing a pacing lead in the RV and a second pacing lead in the coronary sinus that overlies the left ventricle; especially in patients with wide QRS (≥120 ms, best with 160 ms and left bundle branch block pattern), biventricular pacing improves NYHA class by one grade in most patients (≈80%); can be coupled with an implantable cardioverter-defibrillator if needed

Mitral valve regurgitation (MR): secondary MVR is defined as LV dilation with coaptation failure of mitral leaflets; treatment is GDMT; benefits from surgery are indeterminate; repair with transcatheter (eg, MitraClip) is suitable; reducing the regurgitant orifice can reduce the amount of regurgitation; transcatheter passes through the RV, through the atrial septum, then down from the left atrium across the valve for placement of clips; data show improvement in patients with functional or secondary MVR

Diastolic dysfunction (DD): HF with preserved EF (HFpEF) or HF with normal EF (HFnEF); HFpEF — symptoms include LVEF ≥50%, elevated level of NPs (falsely low in obese patients), and ≥1 additional criterion (structural heart disease or DD); in normal doppler pattern of DD, early-filling (E)-wave is greater than atrial contraction (A)-wave; with aging, the E-wave becomes less prominent than the A-wave (grade 1 DD pattern); pseudonormal and restrictive patterns are other variations; HFnEF — seen in older patients (more common in women), and those with diabetes or hypertension with AF; outcomes are similar to those for systolic HF; pharmacotherapy has not been shown to decrease mortality; therapies — diuretic agent, β-blocker to reduce BP, rate control for AF; many drug classes have been shown to benefit systolic dysfunction, but there is no clear evidence of effective treatment for DD

Criteria for referral to HF specialist: need for IV inotropes, class IV HF with persistent NP elevation, end-organ dysfunction, EF ≤35%, >1 hospitalizations per year, persistent edema despite increased diuretics, low BP with normal or high HR, and use of prognostic medication that is intolerable or requires down-titration, especially because of hypotension

Novel approaches: baroreflex activation — shown to be effective in small studies; approved for use in Europe (not in the US); interatrial shunt — studied most extensively in patients with HFpEF who have exercise-induced pulmonary hypertension; creating, essentially, an atrial septal defect allows off-loading of blood; phrenic nerve stimulation — early studies are encouraging; splanchnic nerve block — addresses volume distribution, as opposed to retention; liver, spleen, and colon are areas for volume to be disproportionately placed in patients with HF; blocking splanchnic nerves, which control sympathetic tone, can potentially improve capacitance

Readings

Aziz F, Tk LA, Enweluzo C, et al. Diastolic heart failure: a concise review. J Clin Med Res. 2013;5(5):327-334. doi:10.4021/jocmr1532w; Bakogiannis C, Briasoulis A, Mouselimis D, et al. Iron deficiency as therapeutic target in heart failure: a translational approach. Heart Fail Rev. 2020;25(2):173-182. doi:10.1007/s10741-019-09815-z; Cosín J, Díez J; TORIC investigators. Torasemide in chronic heart failure: results of the TORIC study [published correction appears in Eur J Heart Fail 2002 Oct; 4(5):667]. Eur J Heart Fail. 2002; 4(4):507-513. doi:10.1016/s1388-9842(02)00122-8; Fröhlich H, Torres L, Täger T, et al. Bisoprolol compared with carvedilol and metoprolol succinate in the treatment of patients with chronic heart failure. Clin Res Cardiol. 2017; 106(9):711-721; Heidenreich PA, Fonarow GC, Breathett K, et al. 2020 ACC/AHA clinical performance and quality measures for adults with heart failure. J Am Coll Cardiol. 2020; 76(21):2527-2564; Milinković I, Rosano G, Lopatin Y, et al. The role of ivabradine and trimetazidine in the new ESC HF guidelines. Card Fail Rev. 2016;2(2):123-129. doi:10.15420/cfr.2016:13:1; Ponikowski P, Voors AA, Anker SD, et al. 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2016 Dec 30; 37(27):2129-2200; The Cardiac Insufficiency Bisoprolol Study II (CIBIS-II): A randomised trial. Lancet. 1999; 353(9146):9-13; von Haehling S, Ebner N, Evertz R, et al. Iron deficiency in heart failure: An overview. JACC Heart Fail. 2019; 7(1):36-46.

Disclosures

In adherence to ACCME Standards for Commercial Support, Audio Digest requires all faculty and members of the planning committee to disclose relevant financial relationships within the past 12 months that might create any personal conflicts of interest. Any identified conflicts were resolved to ensure that this educational activity promotes quality in health care and not a proprietary business or commercial interest. For this program, members of the faculty and planning committee reported nothing to disclose.

Acknowledgements

Dr. Shea was recorded virtually at the 56th Annual Northern Michigan Family Medicine Update, held June 23-25, 2021, and presented by University of Michigan Medical School. For information about upcoming CME meetings from this presenter, please visit medicine.umich.edu. Audio Digest thanks Dr. Shea and University of Michigan Medical School for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0 CE contact hours.

Lecture ID:

IM684102

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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