Winston's Heart Failure PDF

**HFrEF -- 7 hours 28 questions- Know what type of Heart Failure the pt has.!!!** **Guideline Resources** II. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guid...

**HFrEF -- 7 hours 28 questions- Know what type of Heart Failure the pt has.!!!** **Guideline Resources** II. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines III. 2023 ACC Expert Consensus Decision Pathway on Management of Heart Failure With Preserved Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee IV. 2024 ACC Expert Consensus Decision Pathway for Treatment of Heart Failure With Reduced Ejection Fraction: A Report of the American College of Cardiology Solution Set Oversight Committee V. 2024 ACC Expert Consensus Decision Pathway on Clinical Assessment, Management, Trajectory of Patients Hospitalized with Heart Failure Focused Update VI. 2024 AHA/ACC/AMSSM/HRS/PACES/SCMR Guideline for the Management of Hypertrophic Cardiomyopathy: A Report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines A. **[Etiology]** +-----------------------------------+-----------------------------------+ | Ischemic (\~ 2/3 of cases) | Increased ventricular stiffness | | | | | - Chronic CHD | - Ventricular hypertrophy | | | | | - Acute ACS | - Infiltrative myocardial | | | disease: amyloidosis, | | Non-ischemic (\~1/3 of cases) | sarcoidosis | | | | | - HTN | - Myocardial ischemia and | | | infarction | | - Idiopathic | | | | | | - Other | | | | - Mitral or tricuspid valve | | | stenosis | | | | | - Valvular abnormalities, | - Pericardial disease: | | myocarditis | pericarditis, pericardial | | | tamponade | | - Toxin (drugs/alcohol), | | | thyroid dysfunction | | +-----------------------------------+-----------------------------------+ B. **[Pathophysiology]** 1. Ability of heart muscle's ability to **[contract]** and / or relax is impaired 2. Heart has to really on **compensatory mechanisms** to maintain adequate CO 3. [Persistent decline], over time and after insult, of CO results in **long term OR chronic** compensatory response C. **[Chronic Compensation]** 4. Results in **VENTRICULAR REMODELING** a. b. c. d. 5. Goal of drug therapy is to REVERSE REMODELING D. [**Neurohormonal** **Model**] 1. [Recognizes the following]: a. b. c. d. 2. KNOW WHICH DRUGS TARGET NEUROHORMONES E. [**Drug** **Targets**] 3. [Norepinephrine (NE)] e. f. g. h. 4. [Angiotensin II (ANG II)] i. j. k. l. m. 5. [Aldosterone (ALD)] n. o. p. q. r. 6. [Natriuretic Peptides] s. t. u. v. 1. Promoting natriuresis/diuresis and vasodilation 2. Decreasing ALD release and inhibition of SNS/RAAS w. F. **[Signs of HF]** +-----------------------------------+-----------------------------------+ | - Ascitesª | - Bibasilar rales\* | | | | | - Hepatomegaly | - S3 gallop | | | | | - Jugular venous distension | - Cheyne-Stokes respiration | | | | | - **Peripheral edema** | - Pleural effusion\* | | | | | | - **Pulmonary edema** | +-----------------------------------+-----------------------------------+ 7. These signs can be evident in both right and left ventricular failure but are often suggestive of injury 8. ª May be difficult to distinguish from central adiposity 9. \* Not super common in chronic HF G. [**Symptoms** **of HF**] +-----------------------------------+-----------------------------------+ | - Systemic congestion | - **Pulmonary Congestion** | | | | | - Abdominal pain | - Cough, esp. at night | | | | | - Anorexia | - **Dyspnea on exertion (DOE)** | | | | | - Bloating | - Fatigue | | | | | - Constipation | - **Orthopnea** | | | | | - Fatigue | - **Paroxysmal nocturnal | | | dyspnea** | | | | | | - Bendopnea | +-----------------------------------+-----------------------------------+ 10. These symptoms can be identified in both right and left ventricular failure but are often suggestive of injury 11. **Bolded** **symptoms** are cardinal symptoms H. [**Biomarker:** **BNP**] 12. B-type natriuretic peptide (BNP) → active proteolytic fragment NT-proBNP x. y. z. a. 13. Lack of decrease in BNP despite compliance = poor prognosis and advanced illness 14. Decreases linked to improvement in remodeling and odds of HF hospitalization or death 15. PEARL \*\*Sacubitril inhibits neprilysin, which degrades BNP = falsely elevated levels\*\* I. **[Labs and Imaging]** 1. [Goals of Therapy] **Reduce mortality** ------------------------------------------ -- **Prevent or minimize hospitalizations** c. d. 2. [Stage A: At Risk for HF] a. 1. HTN 2. CAD (including hyperlipidemia) 3. DM 4. Obesity b. c. d. 3. [Stage B: Patients with Pre-HF] e. f. g. 4. [Stage C: Symptomatic HF] h. i. 5. Daily symptom and weight monitoring 6. Sodium intake 7. Medication adherence 8. Physical activity and exercise training j. 5. [GDMT for HFrEF: Quad Therapy] k. 9. Angiotensin receptor-neprilysin inhibitor (ARNI) 10. Beta blockers (BB) 11. Mineralocorticoid receptor antagonists (MRA) 12. Sodium-glucose cotransporter-2-inhibitors (SGLT2i) 1. Sacubitril/Valsartan (**Entresto**) ====================================== a. b. c. d. 1. Natriuretic peptides 2. Bradykinin, adrenomedullin e. f. 3. At 1-2 weeks and following dose changes, evaluate: a. Blood pressure b. Renal function (BUN, SCr) c. Serum K+ 4. Ensure ACI washout period of 36 hours 5. [Therapy goal] d. Titrate to target dose e. Titration depends on patient 2. ACEI ======= a. b. 1. Ventricular remodeling 2. Myocardial fibrosis 3. Cardiac hypertrophy 4. NE release and vasoconstriction 5. Na and H2O retention c. 6. At 1-2 weeks and following dose changes, evaluate: a. Blood pressure b. Renal function (BUN, SCr) c. Serum K+ 7. Caution with preexisting hypotension, hypoNa, DM, concurrent K+ supplements, or azotemia (3) [Therapy goal] d. Titrate to target dose e. Titration depends on patient f. Some ACEI is better than no ACEI 3. ARBs ======= a. b. c. d. e. 1. Candesartan: **CHARM** 2. Losartan: **OPTIMAAL** 3. Valsartan: **Val**-**HeFT** f. 4. At 1-2 weeks and following dose changes, evaluate: a. Blood pressure b. Renal function (BUN, SCr) c. Serum K+ 5. Caution with preexisting hypotension, hyponatremia, DM, concurrent K supplements or azotemia (3) [Therapy goal] d. Titrate to target dose e. Titration depends on patient 4\. [ARNI, ACEI, ARB Recommendations] a. b. c. d. 5. Beta Blockers ================ a. b. c. 1. Antiarrhythmic effects 2. Prevention/reversal ventricular remodeling 3. Decreased myocyte death from catecholamine-induced necrosis or apoptosis 4. Improved LV systolic function 5. Decreased MVO2 by decreasing HR and LV wall stress 6. Inhibition of plasma renin release d. 7. Only 3 approved agents a. Bisoprolol: beta-1 selective; **CIBIS II** b. Metoprolol Succinate: beta-1 selective; **MERIT-HF** c. Carvedilol: beta-1, beta-2, and alpha-1; **CARVEDILOL HEART FAILURE** e. 8. Titrate dose at 1-2 weeks intervals, as tolerated 9. Use HR and BP to guide dosage changes and as an indicator of BB response 10. Therapy goals d. Titrate to target dose e. Titration depends on patient f. May have to decrease ARNI, ACEI, ARB dose while up-titrating BB f. 11. Should be on ARNI, ACEI/ARB before starting BB 12. Fluid retention or worsening of HF is NOT a reason to withdraw BB therapy permanently 13. Staggering of vasoactive meds may help reduce incidence of hypotension 14. Counsel that symptom improvement may not occur for 2-3 months → do not stop BB 15. Abrupt withdrawal can lead to clinical deterioration → avoid abrupt discontinuation 16. **Toprol CR/XL** CAN be split g. 17. In patients with HFrEF, with current or previous symptoms, use of 1 of the 3 beta-blockers proven to reduce mortality is recommended to reduce mortality and hospitalization (a) Recommended for all patients b. Continuation of Stage B recs c. Cornerstone of GDMT b. c. 1. Inhibit sodium reabsorption 2. Inhibit potassium excretion d. 3. Inhibit cardiac extracellular matrix and collagen deposition 4. Attenuates fibrosis and ventricular remodeling e. 5. Spironolactone (**Aldactone**): **RALES** 6. Eplerenone (**Inspra**): **EPHESUS; EMPHASIS-HF** f. 7. Check K+ and renal function (BUN, SCr) prior to initiation of either agent a. Clinical stability and fluid status will influence monitoring frequency b. Dosage increase of ARNI, ACEI, or ARB should trigger new cycle of monitoring 8. Blood pressure 9. Therapy goal c. Titrate to target dose d. Titration depends on patient g. 10. In patients with HFrEF and NYHA class II to IV symptoms, an MRA is recommended to reduce morbidity and mortality, if eGFR is \> 30 and serum potassium \< 5. Careful monitoring of potassium, renal function, and diuretic dosing should be performed at initiation and closely monitored thereafter to minimize risk of hyperkalemia and renal insufficiency e. Recommended for all patients with appropriate renal function and potassium f. Now considered cornerstone of GDMT (1 of 4 first-line agents) 7. SGLT2 Inhibitors =================== a. SGLT2i reduces death and hospitalization in HFrEF b. SGLT2i shown in multiple trials to improve survival and reduce risk of hospitalization (**by preventing HF**) for HF in patients with DM and established c. Mechanism for cardio renal protection thought to be multifactorial 1. Hemoconcentration 2. Osmotic diuresis and natriuresis 3. Arterial pressure and stiffness reduction 4. Efficient myocardial keystone metabolism 5. **ALL are independent of glucose lowering** d. [Monitoring:] 6. A1C and glucose 7. SCr 8. Blood pressure, volume status a. b. 9. Therapy goal c. e. [Recommendations] 10. In patients with symptomatic chronic HFrEF, and SGLT2i is recommended to reduce hospitalization for HF and cardiovascular mortality, irrespective of the presence of type 2 diabetes d. f. Dapagliflozin: **DAPA-HF** g. Empagliflozin: **EMPEROR-REDUCED** 8. Diuretics ============ a. Diuretics by Class b. [Monitoring:] 1. Daily weights (+/- 3-5 lbs in one week, call MD) 2. Blood pressure 3. BMP plus Mg and Ca 4. Therapy goal a. b. c. [Recommendations] 5. In patients with HF who have fluid retention, diuretics are recommended to relieve congestion, improve symptoms, and prevent worsening HF 6. For patients with HF and congestive symptoms, addition of a thiazide to treatment with a loop diuretic should be reserved for patients who do not respond to moderate-or high-dose loop diuretics to minimize electrolyte abnormalities c. d. d. [Diuretics by Class] +-----------------------------------+-----------------------------------+ | - Only 5-8% Na & Cl | - 20-25% Na reabsorption in | | reabsorption in distal | ascending LoH | | convoluted tubule | | | | - Diuretic effects \> Anti-HTN | | - Anti-HTN effects \> diuretic | effects | | effects | | | | - Effective in renal | | - Minimal effect in patient | impairment; larger doses may | | with renal impairment | be needed | | | | | | - Variable bioavailability | | | | | - HCTZ most often used | | | | | | - 25-50 mg BID | | +-----------------------------------+-----------------------------------+ 9. Hydralazine/ISDN =================== a. Combo (**BiDil**) reduces death and hospitalization in HFrEF b. Benefits established in African American patients c. Combo expensive vs. generic components d. Hydralazine (H) 1. Direct acting arterial vasodilator 2. Reduces SVR and increases SV and CO e. Isosorbide dinitrate (ISDN) 3. Ventilator 4. Reduces preload f. [Monitoring] 5. Blood pressure 6. Avoid imitation in hypotensive or volume depleted patient 7. In symptoms suggestive of SLE obtain: a. b. g. [Therapy goal] 8. Titrate to target dose 9. Titration depends on patient h. [Recommendations] 10. For patients self-identified as African-American with NYHA class III-IV HFrEF who are receiving optimal medical therapy, the combination of hydralazine and isosorbide dinitrate is recommended to improve symptoms and reduce morbidity and mortality 11. For pattens self-identified as African-American with NYHA class III to IV 12. In patients with current or previous symptomatic HFrEF who cannot be given first-line agents, such as ARNI, ACEI, or ARB, b/c of drug intolerance or renal insufficiency, a combination of hydralazine and isosorbide dinitrate might be considered to reduce morbidity and mortality c. d. i. **BiDil:** **A-HeFT** 10. HCN Blocker: Ivabradine (**Corlanor**) ========================================== a. Blockade of hyperpolarization-activated cyclic nucleotide-gated channel responsible for the cardiac pacemaker I~f~ current = selectivity inhibits pacemaker to decrease HR b. Effect most pronounced in the SA node c. Reduction in HR is dose dependent d. No effect on contractility or BP e. Also affects retinal current I~h~ f. [Monitoring] 1. BP 2. HR for bradycardia 3. ECG for atrial fibrillation (4) Therapy goal a. b. g. [Recommendations] 4. For patients with symptomatic (NYHA class II-III) stable chronic HFrEF (LVEF ≤ 35%) who are receiving GDMT, including a beta blocker at maximum tolerated dose, and who are in sinus rhythm with a heart rate of ≥ 70 bpm at rest, ivabradine can be beneficial to reduce HF hospitalizations and cardiovascular death c. h. Ivabradine (**Corlanor**): **SHIFT** 11. a. Soluble guanylate cyclase (sGC) → envy e that catalyzes synthesis of intracellular cGMP b. Regulates vascular tone, contractility and cardiac remodeling c. See impaired NO synthesis in HF and decreased sGC activity d. By directing stimulating sGC and enhancing sGC sensitivity to endogenous NO: 1. Prevent and potentially reverse LV hypertrophy and fibrosis 2. Reduce ventricular afterload via systemic and pulmonary vasodilation 3. Reduce NT-proBNP in dose-dependent fashion e. [Monitoring] 4. Blood pressure 5. CBC 6. Women of child-bearing age need pregnancy test 7. Therapy goal a. b. f. [Recommendations] 8. In selected high-risk patients with HFrEF and recent worsening of HF already on GDMT, an oral soluble guanylate cyclase stimulator (Vericiguat) may be considered to reduce HF hospitalization and cardiovascular death c. d. g. Vericiguat (**Verquvo**): **VICTORIA** 12. h. One large-scale RCT of dig in HF; dig use pre-dates current GDMT i. Used for hospitalization and symptom benefit; no effect on mortality at appropriate doses j. As dig \[ \] increases, so does risk of harm k. Use low doses, particularly in elderly (\> 70 yo, renal dysfunction, low body weight) l. Provide symptom relief and decrease hospitalization in HFrEF m. Improvements in QOL seen within 1-3 months n. Only mortality neutral positive inotrope for HF o. [Monitoring:] 9. Target serum concentration: 0.5-0.9 ng/mL 10. Obtain dig level following: e. f. g. 11. Levels should be drawn 6-12 hours after last dose; no LD necessary in HF treatment 12. Therapy goal h. i. p. [Recommendations] 13. In patients with symptomatic HFrEF despite GDMT (or who are unable to tolerate GDMT) digoxin might be considered to decrease hospitalizations for j. k. O. [**Acute Decompensated Heart** **Failure (ADHF)**] 1. [Signs and Symptoms of ADHF] +-----------------------------------+-----------------------------------+ | - Narrow pulse pressure | - Orthopnea | | | | | - Pulses alterations | - High jugular venous pressure | | | | | - Cool forearms and legs | - Increasing S3 | | | | | - Sleepy, obtunded | - Edema | | | | | - Decreasing renal function / | - Ascites | | increasing SCr | | | | - Rales | | | | | | - Hepatic jugular reflex | | | | | | - Elevated BNP | | | | | | - GI discomfort | +-----------------------------------+-----------------------------------+ a. Also described as advanced HF, end-stage HF, refractory HF b. Management strategies from Stage C no longer effective c. Benefit of water restriction (1.5-2 L/day) in stage D patients with hyponatremia, to reduce symptoms, is uncertain 1. In patients with HFrEF, DHP CCB drugs are **NOT** recommended treatment for HF 2. In patients with HFrEF, Non-DHP CCB are **NOT** recommended 3. In patients with HFrEF, vitamins, nutritional supplements, and hormonal therapy are **NOT** recommended other than to correct specific deficiencies 4. In patients with HFrEF, class IC antiarrhythmic medications and dronedarone may increase the risk of mortality 5. In patients with HFrEF, thiazolidinedione increasing the risk of worsening HF symptoms and hospitalizations 6. In patients with T2DM and high cardiovascular risk, the dipeptidyl peptidase-4 (DPP-4) inhibitors saxagliptin and alogliptin increase the risk of HF hospitalization and should be avoided in patients with HF 7. In patients with HFrEF, NSAIDs worsen HF symptoms and should be avoided or withdrawn whenever possible P. **[Classification of HF by LVEF]** +-----------------------------------+-----------------------------------+ | HFrEF (HF w/ reduced EF) | LVEF ≤ 40% | +-----------------------------------+-----------------------------------+ | HFimpEF (HF w/ improved EF) | Previous LVEF ≤ 40% and a | | | follow-up measurement of LVEF \> | | | | | | 40% | +-----------------------------------+-----------------------------------+ | HFmrEF (HF w/ mildly reduced EF) | LVEF 41-49% | +-----------------------------------+-----------------------------------+ | HFpEF (HF w/ preserved EF) | LVEF ≥ 50% | +-----------------------------------+-----------------------------------+ Q. **[HFmrEF (mildly reduced) Treatment]** 1. 2. R. **[HFimpEF (improved) Treatment]** 3. S. **[Worsening Heart Failure (WHF) Treatment]** 1. Vericiguat ============= a. Consider early, upfront use of vericiguat in combo with QUADRUPLE therapy or after QUADRUPLE optimization, to reduce adverse clinical outcomes \[ = b. Use Vericiguat in place of QUAD medication that is CI or not tolerated c. Unclear if dose escalation of ARNI or MRA vs. initiation of vericiguat offers greater clinical risk reduction, so reasonable to try it 2. Iron ======= a. IV iron should be administered to patients with iron deficiency to improve functional status and patient-reported outcomes and to reduce residual risk of 1. Ferritin \< 100 µg/L or 2. Ferritin 100-299 µg/L with transferrin saturation \< 20% b. **FAIR-HF:** found IV ferric carboxymaltose to improve patient global assessment, c. ESC HF guidelines support use of IV ferric carboxymaltose in patients hospitalized with HF & EF \< 45% with iron deficiency to reduce risk of HF hospitalization T. **[Drug Chart]** +-----------------------+-----------------------+-----------------------+ | **Medication** | **Adverse Effects** | **Contraindications** | +=======================+=======================+=======================+ | Sacubitril/Valsartan | - Hypotension | - Previous | | (**Entresto**) | | angioedema due to | | | - Hyperkalemia | ACEI or ARB | | | | | | | - SCr increase | - Concomitant use | | | | of ACEI or use | | | - Dizziness | within the | | | | previous 36 hours | | | - Cough | | | | | - Concomitant use | | | | of aliskiren in | | | | DM pts | +-----------------------+-----------------------+-----------------------+ | ACEI | | | +-----------------------+-----------------------+-----------------------+ | Captopril | - Hypotension | - Hypersensitivity | | | | | | | - SCr/BUN increase | - Previous | | | | angioedema due to | | | - Hyperkalemia | any ACEI | | | | | | | - Cough | | +-----------------------+-----------------------+-----------------------+ | Enalapril | | | +-----------------------+-----------------------+-----------------------+ | Fosinopril | | | +-----------------------+-----------------------+-----------------------+ | Lisinopril | | | +-----------------------+-----------------------+-----------------------+ | Perindopril | | | +-----------------------+-----------------------+-----------------------+ | Quinapril | | | +-----------------------+-----------------------+-----------------------+ | Ramipril | | | +-----------------------+-----------------------+-----------------------+ | Trandolapril | | | +-----------------------+-----------------------+-----------------------+ | ARBs | | | +-----------------------+-----------------------+-----------------------+ | Candesartan | - Hypotension | - Hypersensitivity | | | | | | | - SCr/BUN increase | - Concomitant use | | | | with aliskiren in | | | - Hyperkalemia | patients with | | | | | | | - Cough | | +-----------------------+-----------------------+-----------------------+ | Losartan | | | +-----------------------+-----------------------+-----------------------+ | Valsartan | | | +-----------------------+-----------------------+-----------------------+ | Beta Blockers | | | +-----------------------+-----------------------+-----------------------+ | Bisoprolol | - Hypotension | - Severe | | | | bradycardia | | | - 1st degree heart | | | | block | - 2nd or 3rd degree | | | | heart block in | | | - Edema | the absence of a | | | | pacemaker | | | - Dizziness | | | | | - Cariogenic shock | | | - Abdominal | | | | pain/diarrhea | - Decompensated | | | | HFrEF | | | | | | | | - Sick sinus | | | | syndrome | +-----------------------+-----------------------+-----------------------+ | Carvedilol | | | +-----------------------+-----------------------+-----------------------+ | Carvedilol CR | | | +-----------------------+-----------------------+-----------------------+ | | | | +-----------------------+-----------------------+-----------------------+ | MRA | | | +-----------------------+-----------------------+-----------------------+ | Spironolactone | - Hyperkalemia | - Spironolactone: | | | | acute renal | | | - Diarrhea | insufficiency, | | | | anuria, or | | | - Impaired renal | significant renal | | | function | dysfunction | | | | | | | - Dizziness | - Eplerenone: serum | | | | K+ \> 5.5 at | | | - Fatigue | initiation, CrCl | | | | \< 30, | | | - Spironolactone: | concomitant use | | | gynecomastia | of strong CYP3A4 | | | | inhibitors | +-----------------------+-----------------------+-----------------------+ | Eplerenone | | | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | SGLT2 Inhibitor | | | +=======================+=======================+=======================+ | Dapagliflozin | - Acute kidney | - T1DM | | | injury | | | | | - Pregnancy | | | - Dyslipidemia | (2nd/3rd | | | | trimester) | | | - Genital mycotic | | | | infection | - DKA | | | | | | | - Hypoglycemia | - Dialysis | | | | | | | - Ketoacidosis | - Volume depletion | | | | | | | - UTI | | +-----------------------+-----------------------+-----------------------+ | Empagliflozin | | | +-----------------------+-----------------------+-----------------------+ | Loop Diuretics | | | +-----------------------+-----------------------+-----------------------+ | Bumetanide | - Hypotension/dizzi | - Hypersensitivity | | | ness | | | | | - Anuria | | | - Fluid loss | | | | | | | | - Hypokalemia, | | | | hypocalcemia, | | | | hypomagnesemia, | | | | hyponatremia, | | | | hipochloremia | | | | | | | | - Hyperuricemia | | | | | | | | - Cramping/diarrhea | | | | | | | | - Nephrotoxicity/ | | | | ototoxicity | | +-----------------------+-----------------------+-----------------------+ | Furosemide | | | +-----------------------+-----------------------+-----------------------+ | Torsemide | | | +-----------------------+-----------------------+-----------------------+ | Ethacrynic Acid | | | +-----------------------+-----------------------+-----------------------+ | Thiazide Diuretics | | | | Used in Combo w/ Loop | | | | Diuretics | | | +-----------------------+-----------------------+-----------------------+ | Metolazone | - Hypotension | - Hypersensitivity | | | | | | | - Dizziness | - anuria | | | | | | | - Gout attacks | - HCTZ: CrCl ≤ 10 | | | | | | | - Hypercalcemia | | | | | | | | - BUN increase | | +-----------------------+-----------------------+-----------------------+ | HCTZ | | | +-----------------------+-----------------------+-----------------------+ | Vasodilators | | | +-----------------------+-----------------------+-----------------------+ | Hydralazine | - Hypotension | - Allergy to | | | | nitrates | | | - HA | | | | | - PDE5i | | | - Dizziness | | | | | - Riociguat | | | - Asthenia | | | | | | | | - Nausea | | +-----------------------+-----------------------+-----------------------+ | Isosorbide Dinitrate | | | +-----------------------+-----------------------+-----------------------+ | **BiDil** | | | +-----------------------+-----------------------+-----------------------+ | HCN Blocker | | | +-----------------------+-----------------------+-----------------------+ | Ivabradine | - Bradycardia | - Acute | | | | decompensated | | | - Atrial | HFrEF | | | fibrillation | | | | | - BP \< 90/50 mm Hg | | | - Phosphenes | | | | (transient | - Sick sinus | | | enhanced | syndrome, | | | brightness in | sinoatrial block, | | | restricted area | or 3rd degree AV | | | of visual field) | block w/o | | | | functioning | | | - Blurred vision | demand pacemaker | | | | | | | | - Resting HR \< 60 | | | | bpm prior to | | | | treatment | | | | | | | | - Severe hepatic | | | | impairment | | | | | | | | - Pacemaker | | | | dependence | | | | | | | | - Concomitant use | | | | with strong | | | | CYP3A4 inhibitors | +-----------------------+-----------------------+-----------------------+ +-----------------------+-----------------------+-----------------------+ | sGC Stimulator | | | +=======================+=======================+=======================+ | | - Symptomatic | **Boxed Warning** | | | | in pregnancy, | | | - Hypotension | breastfeeding | | | | | | | - Syncope | | | | | | | | - Anemia | | +-----------------------+-----------------------+-----------------------+ | Digoxin | | | +-----------------------+-----------------------+-----------------------+ | | - Arrhythmias | Hypersensitivity | | | | Ventricular | | | - Heart block | fibrillation | | | | | | | - Nausea / vomiting | | | | | | | | - Diarrhea | | | | | | | | - Anorexia | | | | | | | | - Visual changes | | | | | | | | - HA | | | | | | | | - Gynecomastia | | | | (long term use) | | | | | | | | - Confusion | | +-----------------------+-----------------------+-----------------------+ U. **[Trials]** +-----------------------------------+-----------------------------------+ | | - **Entresto** | | | | | | - Trial stopped early due to | | | reduction in death and | | | hospitalization for HF | | | | | | - Indicated (initially) for | | | NYHA Class II-IV HFrEF | | | | | | - Data limited in elderly and | | | African-Americans | +-----------------------------------+-----------------------------------+ | | - Studied **Metoprolol CR/XL** | | | | | | - Stopped early due to the | | | following: | | | | | | | | | | | | - Mortality reduced from 11% to | | | 7.2% (vs. placebo); relative | | | reduction of | | | | | | | | | | | | - Reduction in incidence of | | | sudden death (41%) and death | | | from progressive HF (49%) | +-----------------------------------+-----------------------------------+ | | - **Spironolactone** | | | | | | - Stopped early due to the | | | following: | | | | | | | | | | | | - Reduction in death from | | | progressive HF | | | | | | - Reduction in sudden cardiac | | | death | | | | | | | | | | | | - 35% reduction in | | | hospitalizations for | | | worsening HF | | | | | | - Improved NYHA functional | | | class | +-----------------------------------+-----------------------------------+ | | - **Eplerenone** | | | | | | - Reduced mortality | | | | | | | | | | | | - Decrease in sudden death | | | | | | - Decrease in HF and MI | | | | | | Reduced risk for HF | | | hospitalization | +-----------------------------------+-----------------------------------+ | | - **Eplerenone** | | | | | | - Primary endpoint (CV death or | | | HF hospitalization and | | | all-cause mortality) reduced | | | in Eplerenone group | +-----------------------------------+-----------------------------------+ | | - **Dapagliflozin** | | | | | | - Primary endpoint (composite | | | of worsening HF or CV death) | | | was reduced in | | | | | | Indication was expanded to | | | reduce death or HF | | | hospitalization in HFrEF | | | REGARDLESS of presence or absence | | | of DM | +-----------------------------------+-----------------------------------+ | | - **Empagliflozin** | | | | | | - Primary endpoint (CV death or | | | HF hospitalization) was | | | reduce in | +-----------------------------------+-----------------------------------+ | | - **BiDil** | | | | | | - Stopped early due to 43% | | | reduction in all cause | | | mortality | | | | | | - Quality of life, risk for 1st | | | HF hospitalization improved | | | | | | - FDA approved agent for use | | | exclusively in AAs | +-----------------------------------+-----------------------------------+ +-----------------------------------+-----------------------------------+ | | - **Ivabradine** | | | | | | - No effect on mortality but | | | saw decreased | | | hospitalizations | | | | | | - Demonstrated benefit of HR | | | reduction in HF patients | | | | | | - Indicated to reduce risk of | | | hospitalization in patients | | | with stable, symptomatic HF | | | with an EF \< 35%, in NSR | | | with resting HR \> 70 on max | | | tolerated dose BB or BB CI | | | | | | - New AE: phosphenes | +===================================+===================================+ | | - **Vericiguat** | | | | | | - First drug in class; first | | | drug approved specifically | | | for after a HF | | | hospitalization | | | | | | - Composite primary outcome of | | | death from CV causes of 1st | | | HF hospitalization | +-----------------------------------+-----------------------------------+ | | - **IV Iron** | | | | | | - Found **IV ferric | | | carboxymaltose** to improve | | | patient global assessment, | | | NYHA functional class, and | | | 6-minute walk test | +-----------------------------------+-----------------------------------+ **II. HFpEF** 1. [Common]: a. Age b. Female gender c. Atrial fibrillation 1. d. HTN 2. 3. e. Obesity 2. [Others] f. DM g. CAD h. Smoking i. Valvular heart disease C. 1. More challenging than HFrEF = "diagnosis of exclusion" 2. [If LVEF \> 40% diagnosis requires]: a. Clinical signs/symptoms of HF b. Evidence of preserved or normal LVEF (\> 50%) c. Evidence of LV dysfunction, increased filling pressures (per ECHO or cardiac cath), and/or structural changes 3. Can be obtained from **noninvasive** testing d. BNP e. Diastolic function on imaging 4. Or from **invasive** testing, such as hemodynamic measurements 5. [Pearl]: patients with HFpEF tend to have lower natriuretic peptide levels vs. HFrEF. Obese patients also tend to have lower levels. D. +-----------------------+-----------------------+-----------------------+ | H2 | **H**eavy (BMI \> 30 | 2 | | | kg/m2) On ≥ | | | | anti**H**ypertensive | 1 | +=======================+=======================+=======================+ | F | Atrial | 3 | | | **F**ibrillation | | +-----------------------+-----------------------+-----------------------+ | P | **P**ulmonary | 1 | | | hypertension (PASP \> | | | | 35 mm Hg on Doppler | | | | echocardiography | | +-----------------------+-----------------------+-----------------------+ | E | **E**lder (age \> 60 | 1 | | | years) | | +-----------------------+-----------------------+-----------------------+ | F | **F**illing pressure | 1 | | | (E/e \> 9 on Doppler | | | | echocardiography) | | +-----------------------+-----------------------+-----------------------+ F. **[GDMT --- ACC/AHA/HFSA 2022 (]Renewed [Recs from 2013)]** 1. **EMPEROR-PRESERVED** ======================== a. Evaluated Empagliflozin b. [Primary outcome] 1. Composite of cardiovascular death or hospitalization for heart failure c. [Secondary outcome] 2. Occurrence of all hospitalizations for heart failure, including first and recurrent events 3. Rate of decline in the eGFR during double blind treatment 2. **TOPCAT** ============= a. Evaluated Spironolactone (MRA) b. [Rationale] for TOPCAT: no mortality reducing agents in HFpEF c. [Results] of TOPCAT: saw decreases in hospitalizations but no impact on mortality d. [Primary outcome (composite of death from)] 1. 2. 3. e. [Secondary outcomes] 4. 5. 6. 7. 8. 3. **PARAGON-HF** ================= a. Evaluated Sacubitril/Valsartan (**Entresto**) b. [Rationale] for PARAGON-HF: no mortality reducing agents in HFpEF but blockbuster success with drug in PARADIGM-HF c. [Results] of PARAGON-HF: saw decrease in hospitalizations but no impact on mortality d. [Summary] 1. 2. 3. e. Pearl: Sacubitril must be combine with an ARB because neprilysin inhibition increases angiotensin levels, offsetting the vasodilatory effect of sacubitril I. **[Medication List (+ a loop)]** J. **[Summary]** 1. Treat HTN, manage Afib 2. Use diuretics 3. SGLT2 inhibitors (**DELIVER/EMPEROR-PRESERVED**) can be considered 4. MRAs (**TOPCAT**) or ARBs (**CHARM-PRESERVED**) for hospitalization may be considered 5. Sacubitril/Valsartan (Entresto) (**PARAGON-HF**) may be considered