5. Heart failure

Question 1

Definition of heart failure

Answer 1

Clinical condition where the heart is unable to pump blood at a rate sufficient to meet the metabolic demands of the tissues or can only do so at elevated filling pressures; this leads to a forward failure (decreased cardiac output) and backward failure (venous congestion)

Question 2

Weight of normal heart

Answer 2

Weight (0.4-0.5% of total body weight)

1. Males: 300-350g
2. Females: 205-300g

Question 3

Ventricle Free Wall Thickness of normal heart

Answer 3

1. Left ventricle: 1.3-1.5cm

2. Right ventricle: 0.3-0.5cm

Question 4

Physiology of cardiac hypertrophy

Answer 4

1. Increased cardiac workload (due to pressure or volume overload) leading to increased wall stress & cell stretch
2. Cardiac myocytes then induced to undergo hypertrophy
   - Increased protein synthesis to enable assembly of additional sarcomeres
   - Increased number of mitochondria
3. Pattern of hypertrophy depends on nature of stimulus:
   - Pressure overload: concentric hypertrophy, where newly synthesized sarcomeres are assembled in parallel to the long axes of cells, expanding the cross-sectional area of myocytes
   - Volume overload: characterized by dilation, as newly synthesized sarcomeres are assembled in series with existing sarcomeres

Question 5

Associated changes at tissue and cellular level in cardiac hypertrophy

Answer 5

1. Altered gene expression
   - Expression of intermediate-early genes: c-fos, c-myc, c-jun, EGR1
   - Induction of fetal gene program: fetal beta-myosin heavy chain, natriuretic peptides
2. Imbalance in myocardial oxygen consumption & supply
   - Increase in myocyte size not accompanied by a proportional increase in capillary numbers, making oxygen & nutrient supply more tenuous
   - Concomitant increase in metabolic demands of a hypertrophied heart (increased wall tension, contractility) increases myocardial oxygen consumption
   - Hence this predisposes the hypertrophied heart to decompensation
3. Maladaptive changes
   - Myocardial fibrosis
   - Reduced adrenergic drive
   - Decreased calcium availability
   - Impaired mitochondrial function
   - Microcirculatory spasm
   - Apoptosis of myocytes

Question 6

Eventual cardiac dysfunction in cardiac hypertrophy

Answer 6

1. Adaptive/compensatory measures in response to
   increased cardiac workload or impaired cardiac function
   - Hypertrophy +/- dilation
   - Increased sympathetic stimulation (increases myocardial contractility, heart rate & diastolic filling – Frank Starling mechanism)
   - Increased stimulation of renin-angiotensin II- aldosterone system (increases diastolic filling)
2. When capacity to maintain normal cardiac output by these measures is exceeded, heart failure ensues
   - Systolic dysfunction: progressive deterioration of myocardial contractile function (due to ischemic injury , volume overload, valvular disease, hypertension)
   - Diastolic dysfunction: inability to expand & fill sufficiently during diastole (due to massive ventricular hypertrophy, myocardial fibrosis, amyloid deposition, constrictive pericarditis)
3. Arrhythmias

Question 7

Causes of left-sided heart failure

Answer 7

1. Volume overload
   a. Valvular disease (aortic & mitral insufficiency)
   b. High output states (e.g anemia)
2. Pressure overload
   a. Systemic hypertension
   b. Valvular disease (aortic stenosis)
3. Myocardial defect
   a. Ischemic heart disease (myocardial infarction)
   b. Myocardial poisons
   c. Myocarditis
4. Restricted filling
   a. Pericardial effusion
   b. Restrictive pericarditis

Question 8

Pathological effects & complications of left-sided heart failure

Answer 8

1. Backward failure
   a. Left atrial dilation (with increased risk of atrial fibrillation & thromboemolism)
   b. Pulmonary venous hypertension
   c. Pulmonary edema (with associated
   symptoms of dyspnea, orthopnea, paroxysmal nocturnal dyspnea)
2. Forward failure
   a. Decreased cardiac output & hypotension
   b. Activation of neurohumoral mechanisms (including
   RAAS which increases Na+/H2O retention which
   further exacerbates pulmonary edema)
   c. Poor tissue perfusion & oxygenation (leading to pre-
   renal azotemia & hypoxic encephalopathy)

Question 9

Causes of right-sided heart failure

Answer 9

1. Left-sided heart failure
   - Most common cause of right-sided heart failure
   - Due to resultant pulmonary hypertension which eventually places a burden on the right heart
2. Cor pulmonale

Question 10

Pathological effects and complications of right-side heart failure

Answer 10

1. Congestive hepatosplenomegaly
2. Effusions (ascites, pleural effusion)
3. Peripheral subcutaneous edema
4. Venous congestion & hypoxia of organs (e.g. chronic passive congestion of liver)