Cardiovascular Disorders: Hypertension and Heart Failure PDF

# Cardiovascular Disorders ## Cardiovascular Disease * Cardiovascular Disease * Hypertension and heart failure ## Hypertension (HTN) ### Definitions * **Hypertension:** is a condition where the BP is consistently above 140/90 mmHg. * **Essential HTN:** Most patients (90-95% of cases) with hyper...

# Cardiovascular Disorders ## Cardiovascular Disease * Cardiovascular Disease * Hypertension and heart failure ## Hypertension (HTN) ### Definitions * **Hypertension:** is a condition where the BP is consistently above 140/90 mmHg. * **Essential HTN:** Most patients (90-95% of cases) with hypertension have essential hypertension, in which there is no identifiable cause for their chronically elevated BP. * **Secondary HTN:** Patients with secondary hypertension have a specific identified cause for elevated BP. * **Hypertensive crises:** are situations in which measured BP values are markedly elevated (BP >180/120 mm Hg). ### Clinical Presentation and complications: * Patients with uncomplicated primary hypertension are usually asymptomatic. * The most common and important cardiovascular complications associated with hypertension are stroke and myocardial infarction. ### Diagnosis * The diagnosis of hypertension is made only after the average of two or more measurements, taken on separate occasions (repeated after weeks). ## Treatment ### Desired Outcome * Goal blood pressure values are less than 140/90 for uncomplicated hypertension and less than 130/80 for patients with chronic kidney disease, coronary artery disease (myocardial infarction [MI] or angina), or stroke. * **Note:** The current recommendation of American diabetic association is stated that: People with diabetes and hypertension should be treated to a systolic blood pressure (SBP) goal of,<140 mmHg. Lower systolic targets, such as, <130 mmHg, may be appropriate for certain individuals, such as younger patients, if it can be achieved without undue treatment burden. Patients with diabetes should be treated to a diastolic blood pressure (DBP), <80 mmHg. ## Nonpharmacologic Therapy * **Weight reduction:** BMI should be < 25 kg/m². * **Low-fat and saturated fat diet, Low-sodium diet:** < 3.8g sodium chloride per day. * **Dynamic exercise:** at least 30 minutes per day. * **Reduce cardiovascular risk by stopping smoking.** ## Pharmacologic Therapy * **Initial drug selection depends on the degree of BP elevation and the presence of comorbid conditions**. * **Primary antihypertensive agents that are acceptable as first-line options include:** * Thiazide-type diuretics * Angiotensin converting enzyme (ACE) inhibitors * Angiotensin II receptor blockers (ARBs) * Calcium channel blockers (CCBs) * **β-blockers are no longer recommended as 1st line agent for any patient group unless there is a compelling indication (e.g. angina). β-blockers were found to be less effective in reducing the major cardiovascular events, especially stroke, than other antihypertensives.** * **All patients with diabetes and hypertension should be treated with either an ACE inhibitor or an ARB. Both classes provide nephroprotection and reduced CV risk.** * **Thiazides are the preferred type of diuretic for treating hypertension.** Loop diuretics are no more effective at lowering BP than thiazides unless renal function is significantly impaired. They are also a suitable choice if heart failure is present. * **Methyldopa is the most suitable drug choice for use in pregnancy because of its long-term safety record. Calcium channel blockers, and hydralazine are also used. β-Blockers, particularly atenolol, are used less often as they are associated with intrauterine growth retardation.** ## Algorithm for drug sequencing in hypertension: <start_of_image> Age group | Drug options ---------- | -------------- <55 and non-black | A >55 or black | C or D *A = ACE inhibitor; C = calcium channel blocker; D = diuretic* ## Heart Failure ### Definition * Heart failure (HF) is a condition caused by the inability of the heart to pump sufficient blood to meet the metabolic needs of the body. ### Classification * **With systolic failure** (problem in contraction): there is a decreased ejection of blood from the heart during systole. * **With diastolic failure** (problem in the filling of ventricles), filling of the ventricles during diastole is reduced. ### Etiology * The common underlying etiologies in patients with heart failure are coronary artery disease and hypertension. ### Clinical Manifestations #### Left-sided failure * If blood cannot be adequately pumped from the left ventricle to the peripheral circulation, the blood will backs up into the pulmonary alveoli. * The result is the development of pulmonary congestion and edema. * Patients can experience a variety of symptoms (dyspnea (difficult breathing), or shortness of breath (SOB)), related to buildup of fluid in the lungs. * **Exertional dyspnea** occurs when patients describe breathlessness induced by physical activity. * **Orthopnea** is present if a patient is unable to breathe while lying flat on a bed (i.e., in the recumbent position). * **Paroxysmal nocturnal dyspnea (PND)** occurs when patients awaken suddenly with a feeling of breathlessness and suffocation. #### Right-sided failure * When blood is not pumped from the right ventricle, the blood backs up throughout the body producing systemic congestion and edema. * Edema is especially noticeable in the legs (ankles edema) because gravity pulls the fluid into the lower half of the body. ### Heart Failure Symptoms' Classification (table1) | Class | Symptoms | ---------- | -------------- Class I | No symptoms with ordinary activity Class II | Symptoms with ordinary activity Class III | Symptoms with less than ordinary activity Class IV | Symptoms at rest ### Investigations: * **Echocardiogram:** Used to assess LV size, and ejection fraction (EF) (the fraction of the blood pushed during systole from the volume of blood that present at the end of diastole : normally it is more than 50%). * **Chest x-ray:** Useful for detection of cardiac enlargement, pulmonary edema, and pleural effusions. * **ECG:** To assesses the presence of any other cardiac problems, such as arrhythmias. ## Treatment ### Nonpharmacologic Interventions * **Dietary modifications in HF** consist of sodium restriction and sometimes fluid restriction. Patients should routinely practice moderate salt restriction (2–2.5 g sodium or 5-6 g salt per day). Patients should be educated to avoid cooking with salt and to limit intake of foods with high salt content. Fluid restriction may not be necessary in many patients. When applicable, a general recommendation is to limit fluid intake from all sources to less than 2 liters per day. * **Exercise,** while discouraged when the patient is acutely decompensated (acute heart failure), is recommended when patients are stable. Regular low intensity, aerobic exercise that includes walking, swimming, or riding a bike is encouraged, while heavy weight training is discouraged. * **Modification of classic risk factors, such as tobacco and alcohol consumption, is important to minimize the potential for further aggravation of heart function.** ### Pharmacologic Treatment #### Systolic Heart Failure * **Agents with proven benefits in improving symptoms, slowing disease progression, and improving survival (reduce mortality) in chronic HF include:** * ACE inhibitors * ARBs * ẞ-adrenergic blockers * aldosterone antagonists * angiotensin-receptor/neprilysin inhibitor (ARNI) [(sacubitril/valsartan (Entresto®)] ##### Neprilysin inhibitors: * **Neprilysin** is an enzyme that involved in degradation of many peptides including natriuretic peptides, bradykinin and adrenomedullin. * **Inhibition of neprilysin** increased the availability of these peptides which exert favorable effects in heart failure (e.g. vasodilatation and natriuretic actions). * **Because neprilysin also degrades angiotensin II, a neprilysin inhibitor must be combined with agent that blocks rennin-angiotension system.** Since ACE and neprilysin each breakdown bradykinin, inhibiting both enzyme lead to significant increase in the risk of angioedema. For that reason the neprilysin inhibitor-ARB (Sacubitril/Valsartan) combination was developed. * The updated American College of Cardiology/American Heart Association (ACC/AHA)guideline in 2016 recommend using an ACE inhibitor, ARB, or ARNI in combination with background therapy, including beta-blockers and aldosterone antagonists, to reduce morbidity and mortality. * For patients with chronic symptomatic class II or III HF with reduced ejection fraction who tolerate an ACE inhibitor or ARB, the guidelines recommend replacing the existing ACE inhibitor or ARB with an ARNI to reduce morbidity and mortality. #### Angiotensin-Converting Enzyme(ACE) Inhibitors: * The updated (ACC/AHA)guideline in 2016 recommend using an ACE inhibitor (like captopril, lisinopril, enalapril,.....), ARB, or ARNI in combination with background therapy, including beta-blockers and aldosterone antagonists, to reduce morbidity and mortality. * ACE inhibitors should be initiated at low doses, followed by increments in dose if lower doses have been well tolerated. #### B-Blockers: * The ACC/AHA guidelines state that β-blockers should be prescribed to all patients with stable systolic HF unless they have a C/I. * Extended-release metoprolol succinate, carvedilol, and bisoprolol are FDA approved for use in HF. * Metoprolol and bisoprolol are both partially selective ẞ1-lockers, and carvedilol is a mixed al- and nonselective B-blocking agent. * β-Blockers should be initiated in stable patients who have no or minimal evidence of fluid overload. Because of their negative inotropic effects, ẞ-blockers should be started in very low doses with slow upward dose titration (in a 'start low, go slow' fashion) to avoid symptomatic worsening. #### Angiotensin II Receptor Blockers (ARBs): * Although some data suggest that ARBs produce equivalent mortality benefits when compared with ACE inhibitors, the ACC/AHA guidelines recommend use of ARBs only in patients who are intolerant of ACE inhibitors. #### Aldosterone Antagonists: * There is evidence that aldosterone mediates some of the major effects of RAAS activation, such as myocardial remodeling and fibrosis, as well as sodium retention and potassium loss at the distal tubules. * Currently low-dose aldosterone antagonists (e.g. 25 mg/day spironolactone) should be added for: * Patients with symptoms of moderate to severe heart failure (NYHA class III-IV) who are receiving standard therapy; and * Those with LV dysfunction early after MI (where heart failure occurs in the first 4 weeks after an acute myocardial infarction). #### Diuretics: * Loop and thiazide diuretics have not been shown to improve survival in heart failure. Consequently, diuretic therapy (in addition to sodium restriction) is recommended in all patients with clinical evidence of fluid retention (peripheral and pulmonary edema). Patients who do not have fluid retention would not require diuretic therapy. * Loop diuretics (furosemide, bumetanide, and torsemide) are the most widely used diuretics in HF . #### Nitrates and Hydralazine: * Nitrates (e.g., ISDN) and Hydralazine are combined in the treatment of HF because of their complementary hemodynamic actions. * **Hydralazine** is a potent arterial dilating agent that decrease afterload. * **Nitrates** have venous dilating properties that decrease preload. * The combination may be reasonable for patients with persistent symptoms despite optimized therapy with an ACE inhibitor (or ARB) and ẞ-blocker. The combination also appropriate as first-line therapy in patients unable to tolerate ACE inhibitors or ARBs. #### Digoxin: * Digoxin does not improve survival in patients with HF but does provide symptomatic benefits only. * Current recommendations are for the addition of digoxin for patients who remain symptomatic despite an optimal HF regimen consisting of an ACE inhibitor or ARB, β-blocker, and diuretic. * Digoxin is also prescribed routinely in patients with HF and concurrent atrial Fibrillation (AF) to slow ventricular rate regardless of HF symptoms. #### Heart Failure Caused by Diastolic Dysfunction * **Diastolic dysfunction,** an inadequacy of ventricular relaxation and impaired LV filling. * **Diastolic dysfunction** is characterized by a normal or near-normal LVEF (40% to 60%). For symptomatic patients, diuretics in conjunction with salt restriction are indicated initially to relieve congestive symptoms. Thereafter, β-adrenergic blockers, calcium channel blockers (e.g., verapamil), or ACE inhibitors, and ARBs, may be beneficial. * **Note:** Unlike in systolic HF, nondihydropyridine calcium channel blockers (diltiazem and verapamil) may be useful in heart failure caused by diastolic dysfunction. * **A recent study did not find favorable effects with digoxin in patients with mild to moderate diastolic HF**. Therefore, the role of digoxin for symptom management and HR control in these patients is not well established. ### References 1. Joseph T. DiPiro, Robert L. Pharmacotherapy: A Pathophysiologic Approach, 10th Edition.2017. 2. Zdanowicz, Martin M. Essentials of pathophysiology forpharmacy. © 2003 by CRC Press LLC. 3. Roger Walker. Clinical Pharmacy and Therapeutics. Fifth edition 2012. 4. Leon Shargel, Alan H. Mutnick. Comprehensive pharmacy review. Fifth edition 2007 5. Marie A. Chisholm-Burns.Pharmacotherapy Principles & Practice. 4th edition. 2016. 6. 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