see also: [[Pulmonary oedema|APO]], [[Right heart failure]] > [!Key Points] # Ejection fraction **Ejection fraction** is the percentage of ventricular volume that is ejected per heartbeat. The lower limit of normal for the LVEF is **50 - 55%.** **EF = (EDV - ESV)/ EDV** # HFrEF **HFrEF** corresponds to the older terminology of **systolic heart failure** - or a failure of contractility.   LVEF < 40 % (european) LVEF <50% (australian) + symptoms of heart failure # HFpEF **HFpEF** corresponds to the older terminology of **diastolic heart failure.**  Diastolic function incorporates two components: - **LV compliance** (the inverse of stiffness), and - **active ventricular relaxation**. Reduced ventricular compliance and abnormal ventricular relaxation may both result in **increased left-sided intra-cavity filling pressure**. symptoms of heart failure + LVEF >50% + structural heart disease (eg LA enlargement, LV hypertrophy) and/or diastolic dysfunction (BNP or ECHO) # Four types of "acute heart failure" ## Acute pulmonary oedema See also: [[Pulmonary oedema|APO]] - It is characterised by the acute (often within minutes or hours) development of pulmonary oedema as the dominant clinical feature of left heart failure with **redistribution** of fluid into the pulmonary interstitium and then alveolar flooding. - ## Cardiogenic shock - Cardiogenic shock is typically characterised by the acute development of reduced cardiac output (cardiac index < 2.2 L/min/m2) and hypotension (systolic blood pressure < 90 mm Hg) in the setting of heart failure (PCWP > 18 mm Hg) to the point where end organ perfusion is compromised. - Cardiogenic shock most commonly results from a large acute myocardial functional insult (e.g., acute myocardial infarction (MI) or acute fulminant myocarditis) or a catastrophic cardiac structural insult (e.g., acute torrential valvular regurgitation). - Cardiogenic shock requires inotropic support by drugs or mechanical assist devices, and frequently intubation and ventilation. ## Acute decompensated heart failure This is the entity most commonly referred to as “acute heart failure”. It is essentially a relatively acute decompensation in a previously stable patient, due to a precipitating event. Treatment involves diuresis and attention to the underlying precipitant. ## Right heart failure see also: [[Right heart failure]] This refers to solitary (or at least predominant) failure of the right heart. Rare causes are right ventricular (RV) infarction or isolated tricuspid valve pathology; however, the most common cause of right heart failure is right heart pressure overload. The right heart is a low-pressure system, and consequently it is particularly sensitive to high afterload (pulmonary hypertension). Pulmonary hypertension is a consequence of many prevalent chronic diseases # Pathophysiology Heart Failure  is a syndrome characterized by the activation of 3 neurohumeral responses: 1. Sympathetic nervous system (SNS) 2. Renin - Angiotensin - Aldosterone system (RAAS)  3. The natriuretic peptide system (NPS). **Excessive** activation of the **SNS** and the **RASS** can lead to **detrimental** results in heart failure.  Pharmacological interventions have therefore been developed to counteract the neuroendocrine overregulation of: - The  SNS (with **β-blockers**). - The RAAS (with **ACE inhibitors, ARBs** and **mineralcorticoid antagonists** or **MRAs**) It is now known that the natriuretic peptide system _counter regulates_ the _detrimental_ effects of the upregulation of the SNS and the RAAS More recently a novel class of **neprilysin inhibitors** have been developed to enhance the NP system   - the **angiotensin receptor neprilysin inhibitors** or **ARNIs*.  The first of this new class is **sacubitril - valsartan**  (Entresto) Sustained activation of the renin angiotensin aldosterone system results in vasoconstriction, renal sodium and fluid retention, activation of cellular growth and proliferation, and subsequent maladaptive cardiovascular remodelling.  Valsartan inhibits detrimental cardiovascular and renal effects of angiotensin II by selectively blocking the AT1 receptor, and also inhibits angiotensin II dependent aldosterone release. ## BNP ![[BNP#With respect to “ruling out” heart failure, current Australian guidelines say:]] ![[BNP#With respect to “ruling in” heart failure, current Australian guidelines say:]] ## CXR Radiographic signs of heart failure include: - Upper lobe blood diversion is usually the first radiographic sign of heart failure. - Interstitial edema, this is represented as fine linear opacities; (peripherally placed basal ones are termed Kerly B lines, whilst more central ones are termed Kerly A lines). ![[Pasted image 20230515220310.png]] # Pharm treatment The Pharmacotherapy of **chronic heart failure** involves 4 principle **classes** of drugs: ## 1. Diuretics and MRAs - lasix - spironolactone or eplerone (Mineralocorticoid receptor antagonist) ### MRAs Spironolactone or eplerenone are recommended in all patients who remain symptomatic, despite treatment with an ACEI and a beta-blocker, with HFrEF and LVEF ≤ 35%, to reduce mortality and HF hospitalization. **Caution should be exercised when MRAs are used in patients with impaired renal function** and in those with serum potassium levels .5.0 mmol/L. Regular checks of serum potassium levels and renal function should be performed according to clinical status. ### Diuretics Diuretics are recommended to reduce the **signs and symptoms** of congestion in patients with HFrEF, but their effects on mortality and morbidity have **not** been studied in RCTs Diuretics appear to improve symptoms including exercise capacity. Loop diuretics produce a more intense and shorter diuresis than thiazides, although they act synergistically and the combination may be used to treat resistant oedema.  However, adverse effects are more likely and these combinations should only be used with care.  ==The aim of diuretic therapy is to achieve and maintain euvolaemia with the lowest achievable dose.== ## 2. Sympathetic nervous system  (**SNS**) antagonists - Beta blockers  - Ivabradine  ### Beta blocker Beta-blockers reduce mortality and morbidity in symptomatic patients with HFrEF, despite treatment with an ACEI and, in most cases, a diuretic. There is consensus that **beta-blockers and ACEIs** are **complementary**, and ==can be started together as soon as the diagnosis of HFrEF is made.==  There is no evidence favouring the initiation of treatment with a beta-blocker before an ACEI has been started. Beta-blockers should be initiated in clinically stable patients at a low dose and gradually up-titrated to the maximum tolerated dose. In patients admitted due to acute HF (AHF) beta-blockers should be cautiously initiated in hospital, once the patient is stabilized. The **specific** beta blockers which are recommended for adjunctive treatment in **heart failure** are: - Carvedilol - Bisoprolol - Metoprolol succinate - Nebivolol ### Ivabradine Ivabradine should be considered to reduce the risk of HF hospitalization and cardiovascular death in ==symptomatic patients with LVEF ≤ 35%==, in **sinus rhythm** and a **resting heart rate ≥ 70 bpm** who are **unable to tolerate** or have **contra-indications** for a **beta-blocker**. Patients should also receive an ACE-I (or ARB) and an MRA (or ARB). Ivabradine should also be considered to reduce the risk of HF hospitalization or cardiovascular death in symptomatic patients with LVEF ≤ 35%, in sinus rhythm and a resting heart rate ≥70 bpm **despite** treatment with an evidence-based dose of beta-blocker (or maximum tolerated dose below that), ACE-I (or ARB), and an MRA (or ARB) ## 3. Renin - Angiotensin - Aldosterone system (**RAAS**) antagonists - Angiotensin converting enzyme inhibitors (ACEIs)  - Angiotensin receptor blockers (ARBs)   - Mineralcorticoid antagonists (MRAs) ### ACE-I Treatment is commenced with ACEIs and beta blockers. ACEIs have been shown to ==reduce mortality and morbidity in patients with HFrEF== and are recommended (unless contraindicated or not tolerated) in all symptomatic patients. ACEIs should be up-titrated to the **maximum tolerated dose** in order to achieve adequate inhibition of the renin - angiotensin - aldosterone system (RAAS). There is evidence that in clinical practice the majority of patients receive suboptimal doses of ACEI. ### ARBs An ARB is recommended to reduce the risk of HF hospitalization and cardiovascular death in symptomatic patients **unable to tolerate an ACE-I** (patients should also receive a beta-blocker and an MRA). An ARB may be considered to reduce the risk of HF hospitalization and death in patients who are symptomatic despite treatment with a beta-blocker who are unable to tolerate an MRA. ## 4. Natriuretic peptide agonists (in combination with **valsartan**) - Neprilysin antagonists with ARBs or angiotensin receptor - neprilysin inhibitors (ARNIs) ### Entresto (sacubitril-valsartan) Sacubitril-valsartan is recommended as a replacement for an ACE-I (or ARB) to further reduce the risk of HF hospitalization and death in ambulatory patients with HFrEF who remain symptomatic despite optimal treatment with an ACE-I, a beta-blocker and an MRA ## others - Hydralazine and isosorbide dinitrate - Digoxin - SGLT2-i ### Hydralazine and isosorbide dinitrate Hydralazine and isosorbide dinitrate may be considered in symptomatic patients with HFrEF who can tolerate neither an ACE-I nor an ARB (or they are contra-indicated) to reduce the risk of death. ### Digoxin Digoxin may be considered in symptomatic patients in sinus rhythm despite treatment with an ACE-I (or ARB), a beta-blocker and an MRA, to reduce the risk of hospitalization (both all-cause and HF-hospitalizations). In patients with symptomatic HF and AF, digoxin may be useful to slow a rapid ventricular rate, but it is only recommended for the treatment of patients with HFrEF and AF with rapid ventricular rate when other therapeutic options cannot be pursued. Of note, the optimal ventricular rate for patients with HF and AF has not been well established, but the prevailing evidence suggests that strict rate control might be deleterious. A resting ventricular rate in the range of 70 - 110 bpm is acceptable. > use of these drugs in **chronic heart failure** is guided by the ejection fraction, not the preserved vs reduced distinction # Drugs not to use **calcium channel blockers** **Non-dihydropyridine** calcium-channel blockers (**CCBs**) are **not** indicated for the treatment of patients with HFrEF.  ==**Diltiazem** and **verapamil** have been shown to be **unsafe** in patients with HFrEF== With regard to **dihydropyridine** CCBs; some are known to increase sympathetic tone and they may have a negative safety profile in HFrEF.  There is only evidence on safety for **amlodipine** and **felodipine** in patients with HFrEF, and they can be used only if there is a **compelling** indication in patients with HFrEF. # Specific treatment regimines ## EF < 40% Recommended (as tolerated): 1. ACEI or ARB or ARNI -Valsartan 2. Beta - blocker &/or Ivabradine 3. MRA Consider: 1. Diuretics 2. Hydralazine and isosorbide dinitrate (as alternative to ACEI or ARB) 3. Digoxin, may be considered in symptomatic patients in sinus rhythm or rapid AF despite treatment with an ACE-I (or ARB), a beta-blocker and an MRA ## EF 41-49% **Consider** (depending on exact value - all else being equal):  1.  ACEI **or** ARB **or** ARNI -Valsartan  2.  Beta - blocker &/or Ivabradine  3.  MRA 4.  Diuretics  5.  Hydralazine and isosorbide dinitrate (as alternative to ACEI or ARB) - Digoxin, may be considered in symptomatic patients in sinus rhythm or rapid AF despite treatment with an ACE-I (or ARB), a beta-blocker and an MRA ## EF >50% **No treatment has yet been shown, convincingly, to reduce morbidity or mortality in patients with HFpEF** Therapy may however be given for symptoms and/or for comorbidities   Low dose spironolactone may be _considered_ to decrease HF hospitalization. ## Patients with AF and Heart Failure Pharmacological therapy aiming for a resting ventricular rate of 60-100 bpm should be considered in patients with HF associated with AF and a rapid ventricular response Beta-Blockers and/or digoxin are generally favoured for ventricular rate control. Consider non-dihydropyridine calcium entry blockers in patients with HFpEF to control the ventricular rate of AF; however, these drugs should be avoided in patients with HFrEF. Catheter ablation for AF (either paroxysmal or persistent) should be considered in patients with HFrEF associated with an LVEF ≤ 35%, who present with recurrent symptomatic AF, to decrease mortality and hospitalisation for HF. Consider oral amiodarone in patients with HF associated with AF, to facilitate attainment and maintenance of sinus rhythm (with or without electrical cardioversion), improve symptoms, or guide decisions regarding the need for more invasive approaches (e.g., AF catheter ablation or atrioventricular node ablation). ![[Pasted image 20230515192312.png]] # Device Treatment ## Cardiac resynchronization therapy (CRT) Resynchronisation of ventricular contraction is achieved by pacing both the left and the right ventricles simultaneously. The benefit is greater in patients with a broader QRS duration, and in some studies for left bundle branch block morphology and prolonged PR interval.