1. What is heart failure? impaired ability of left ventricles to fill with (diastole) or eject (systole) blood. HF is characterized by impaired LV function and reduced LV reserve. cardinal symptoms are dyspnea, fatigue, and fluid retention.
2. What are the 2 types of HF? HF is generally categorized on the basis of LV ejection fraction (LVEF)
3. HF with reduced ejection fraction (HFrEF): It is systolic dysfunction which is a pumping problem characterized by an enlarged left ventricle (EF ≤ 40%) mostly due to CAD. Most clinical trials have been conducted in patients with HFrEF.
4. HF with preserved ejection fraction (HFpEF): It is diastolic dysfunction which is a filling problem mostly due to HTN. There is no strong consensus on the definition of HFpEF or its treatment, despite the fact it represents up to 50% of all HF patients.
5. What is the leading reason for HF with reduced ejection fraction (HFrEF), also called systolic dysfunction? CAD

1. What is decompensated HF? If the heart becomes severely damaged, no amount of compensation, either by sympathetic nervous reflexes or by fluid retention, can make the excessively weakened heart to pump a normal cardiac output. As a consequence, the cardiac output cannot rise high enough to make the kidneys excrete normal quantities of fluid. Therefore, fluid continues to be retained, the person develops more and more edema, and this state of events eventually leads to death. This condition is called decompensated heart failure. Thus, a major cause of decompensated heart failure is failure of the heart to pump sufficient blood to make the kidneys excrete the necessary amounts of fluid every day. The patient has fluid overload in the lungs, and as they are walking, they are huffing and puffing. When acute symptoms worsen by volume overload it is called decompensated HF.
2. What are the symptoms of decompensated HF? ankle swelling because of fluid overload, shortness of breath due to fluid retention in lungs. 
3. What are the main reasons for decompensated HF? An attack of decompensation can be caused by underlying medical illness, such as myocardial infarction, an abnormal heart rhythm, infection, or thyroid disease or any traumas.
4. How is decompensated HF treated? 
5. First the fluid is drained out of body and the patient is stabilized. 
6. After patient’s stabilization we can use BB and CCB. But we never and never start with CCB or BB in middle of crisis

1. How does the body compensate in heart failure?
2. The nervous system: If body senses that the brain and vital organs aren't receiving enough blood the sympathetic nervous system releases catecholamines into the bloodstream. These substances cause the blood vessels to constrict and speed up the heart rate. At the same time, the arteries supplying the brain and vital organs widen to carry the increased blood flow.     
3. Hormone systems: When the body thinks it needs more fluid in its blood vessels, it releases specific chemicals (renin, angiotensin, and aldosterone) that cause the blood vessels to constrict. In addition, these hormones cause the body to retain more sodium and water. This adds fluid to blood circulatory system. This fluid becomes part of the blood circulating throughout blood system.
4. Heart:

Stroke volume. 

1. What are the clinical symptoms of HF? cardinal symptoms are dyspnea, fatigue, and fluid retention.
2. Dyspnea & Orthopnea: shortness of breath Due to pulmonary edema; sudden nocturnal dyspnea, orthopnea, tachypnea
3. Fatigue, Weakness & Exercise intolerance
4. Peripheral edema: due to fluid retention that causes weight gain & ankle swelling
5. Hypotension: Fatigue, cyanosis, confusion, chest pain
6. Systemic congestion: Jugular venous congestion, hepatomegaly, ascites, N/V
7. Cough
8. Abdominal distension     
9. Nocturia     
10. Cool extremities
11. What are the Laboratory Investigations for Evaluation of Patients with Heart Failure?

1. What are the different classifications of HF?

1. What are the main risk factors for Heart Failure?

1. What are the nonpharmacological approaches for HF therapy, control and prevention? Memorize the numbers.
   1. Manage concomitant disease states (coronary artery disease and other vascular diseases, diabetes mellitus, dyslipidemia, hypertension, obesity, sleep apnea, supraventricular and ventricular arrhythmias)
   2. Salt Restrictions: < 2-3 g Na+/day (patients must watch diet). If more than one stroke occurrence then 1-2g per day.
   3. Fluid restrictions: 2 L/day from all sources
   4. Reduce alcohol intake: patients are often limited to one drink/day
   5. Exercise moderately: if stable HF to improve exercise tolerance
   6. Monitor weight frequently: common to gain >4kg from edema
   7. Immunization: annual influenza & pneumococcal vaccines in all patients
   8. Treat risk factors: e.g.HTN
   9. Smoking cessation
   10. PCI or CABG in symptomatic ischemia
   11. ICD if history of sudden cardiac arrest or ventricular fibrillation

1. What are pharmacologic therapeutic choices in Reduced Ejection Fraction (HFrEF)?  the cornerstone of therapy for HFrEF in all patients with an LVEF ≤40% (NYHA class I–IV) has been long-term treatment with the combination of an angiotensin converting enzyme (ACE) inhibitor and a beta-blocker

1. What are the beta-blockers with mortality benefits? bisoprolol, carvedilol, metoprolol succinate (not available in Canada)
2. Which ARB are used in HF? VLC  Valsartan, Losartan, Candesartan
3. What is HFrEF? Reduced ejection fraction (HFrEF) – also referred to as systolic heart failure.

                  Start with triple therapy as 1st line

When switching from ACEi/ARB to ARNI there is a wash-up period of 36hrs to minimize angioedema risk

Potassium level must be 3.5-5. Potassium level above 5 is considered hyperkalemia

1. How do you treat HFerEF?
2. Start triple therapy with ACEi/ARB + BB + MRA
3. If condition persists with HR < 70 into class II-IV change to ARNI + BB + MRA
4. If condition persists with HR > 70 into class II-IV change to Ivabradine + ARNI + BB + MRA
5. For Africans it can start with quadrable therapy hydralazine + ACEi/ARB + BB + MRA

1. In which conditions you should avoid MRA?
2. K>5
3. CrCl < 30ml/min
4. Serum creatinine >221mmol/l
5. What is the treatment for HFpEF? There isn’t a specific preference for HFpEF
6. Identify and treat underlying factors e.g. ischemia or valvular disease
7. Treat HTN
8. Consider loop diuretics if indicated
9. Consider ACEi, ARB and/or BB if indicated
10. Consider anticoagulation in patients with atrial fibrillation if indicated
11. Consider MRA e.g. spironolactone if K+ < 5.0 mmol/L and eGFR > 30 mL/min

1. Which medications have been shown to reduce hospitalizations in heart failure with preserved ejection fraction (HFpEF) patients? Candesartan + spironolactone
2. Which patients are at greatest risk of hyperkalemia? RAAS-inhibiting agents used in the management of heart failure, such as ACE inhibitors, ARBs, ARNIs and MRAs, may lead to hyperkalemia if treatment is not properly monitored.
3. Patients with moderate to severe renal dysfunction
4. High baseline potassium,
5. Patients with diabetes mellitus
6. Those receiving potassium-sparing diuretics
7. Those receiving ACEi/ARB
8. What is aldosterone? Aldosterone, a steroid hormone secreted by adrenal glands. Aldosterone serves as the principal regulator of the salt and water balance and K excretion thus it is categorized as a mineralocorticoid.
9. What is biological function of aldosterone? The biological action of aldosterone is to increase the retention of sodium and water and to increase the excretion of potassium by the kidneys
10. What is aldosterone secretion mechanism of function? Production of aldosterone in adrenal cortex is regulated by the renin-angiotensin system. Renin is secreted from the kidneys in response to variations in blood pressure, Renin acts on a protein circulating in the plasma called angiotensinogen, cleaving this substance into angiotensin I. Angiotensin I is subsequently converted to angiotensin II, which stimulates the release of aldosterone from the adrenal glands.
11. How do you treat decompensated heart failure? 
12. Intravenous loop diuretics (furosemide) are recommended in patients with signs and symptoms of fluid retention
13. Use combinations of diuretics, or add a vasodilator such as nitroglycerin or nitroprusside for hospitalized patients who do not respond to intravenous furosemide.
14. Take care to prevent cyanide and thiocyanide toxicity with nitroprusside
15. Dobutamine: In patients with low cardiac output, milrinone or dobutamine is indicated if the systolic blood pressure is >90 mm Hg;1 dobutamine is preferred if the systolic blood pressure is <90 mm Hg.
16. What are the main indications of mineral corticosteroids - MRA? Spironolactone, Eplerenone 
17. Patients with acute myocardial infarction (MI) with an ejection fraction (EF) of < 40%, and symptoms of heart failure 
18. Patients with acute MI with an EF of <30% without symptoms of heart failure in the presence of diabetes
19. What do you suggest to a patient who experiences gynecomastia because of spironolactone? Use Eplerenone instead. Eplerenone dose not have gynecomastia side effect.
20. How do B-blockers block renin-angiotensin system? As increased sympathetic activity can stimulate renin release, beta blockers reduce release by antagonizing the sympathetic nervous system (SNS) and therefore prevent the activation of RAAS. Normally, RAAS would increase sodium and water retention and therefore increased venous pressure (increased preload). Beta blockers can reduce preload and ultimately cardiac output. By inhibiting sympathetic nervous system and RAAS activation, beta blockers can also prevent cardiac remodeling.
21. How do MRAs block renin-angiotensin-aldosterone system? Aldosterone levels may be elevated in patients with heart failure due to the overactivity of renin-angiotensin-aldosterone system. This is due to reduced cardiac output. When cardiac output is reduced, renal blood flow is reduced, activating RAAS. This will ultimately increase aldosterone levels, causing water and sodium retention. Therefore, an aldosterone antagonist, such as spironolactone, can reduce aldosterone levels and cardiac remodeling.
22. How does ACEi block renin-angiotensin-aldosterone system? ACE inhibitors inhibit the conversion of angiotensin I to angiotensin II and in doing so, blocks a part of the RAAS. This results in a reduced sodium and water retention and therefore reduced preload. ACE inhibitors also reduce afterload by vasodilating arteries to reduce systemic resistance. All these changes lead to an increase in cardiac output and a reduction in cardiac remodeling.
23. How does ARB block renin-angiotensin-aldosterone system? ARBs block the binding of angiotensin II to the angiotensin I receptor and in doing so, blocks a part of the RAAS. ARBs also share the same effects on the RAAS as ACE inhibitors. However, ARBs do not affect kinin metabolism, resulting in a lower incidence of cough as an adverse effect, compared to ACE inhibitors.

1. Metoprolol & Digoxin
2. Metoprolol: The formulation of metoprolol available in Canada (metoprolol tartrate) has not been shown to reduce mortality in a randomized trial of patients with HF, is not available in a commercial dosage form that is suitable for initial treatment of HF and is not included in Canadian guidelines. Nevertheless, metoprolol tartrate is the preferred beta-blocker in pregnant and breastfeeding women
3. Most experts agree that HF with an LVEF <35–40%, or NYHA functional class III or IV, are contraindications to pregnancy because of the high risk of cardiovascular events and mortality.
4. Sodium and fluid restrictions are recommended to minimize signs and symptoms of hypervolemia.
5. Digoxin can also be used safely, but higher doses may be required in pregnant women
6. Avoid ACE inhibitors, ARBs and MRAs during pregnancy because they are known teratogens.

1. Metoprolol, Spironolactone, ACE
2. Ivabradine should be avoided during breastfeeding as it is not known if it is excreted in breast milk.

1. Hypotension or worsening renal function when initiating or increasing the dose of an ACE inhibitor usually indicates the need to reduce the dose of a diuretic.
2. Metoprolol tartrate is the preferred beta-blocker in pregnant and breastfeeding women
3. Cough is a symptom of HF decompensation. Careful evaluation is necessary when evaluating a cough in a patient receiving an ACE inhibitor.
4. Signs and symptoms of heart failure are very similar to COPD. However, edema in lower extremities is not a sign/symptom of COPD. If it occurs in COPD patients, it usually relates to HF or pulmonary hypertension. In addition, BNP is a cardiac biomarker.
5. Although diabetes is a risk factor for heart failure, but an elevated blood glucose level is not a biomarker for heart failure.