1. Define all unknown terms.

2. Cite the primary clinical problem (not the diagnosis).

Shortness of Breath (Dyspnea, Breathlessness)

3. Develop a differential diagnosis for this clinical problem on the basis of history. What is your diagnosis? Describe the data from the history which supports your diagnosis, keeping in mind the concepts of sensitivity, specificity, predictive value. Apply this strategy in ruling out other causes of the clinical problem. 

• Congestive Heart Failure: Orthopnea, PND, associated with edema legs.

• Adult respiratory distress syndrome: Non-cardiogenic pulmonary edema. Normal capillary wedge pressure. Leaky pulmonary capillaries.

• Chronic Bronchitis: Cough and spit for 3 months for two consecutive years. In most strong smoking history.

• Pulmonary Emphysema: Older patient. Progressive shortness of breath over time. Strong smoking history.

• Asthma: Intermittent episodes of shortness of breath associated with wheezing. Strong atopic history. Normal in between episodes.

• Diffuse Interstitial Lung Disease: Older patient. Progressive shortness of breath associated.

• Spontaneous Pneumothorax: Acute onset of shortness of breath, with sharp chest pain.

• Acute Pulmonary Embolism: Varied presentation from acute to chronic shortness of breath. With a predisposing situation for thrmboembolic process. High index of suspicion for the diagnosis crucial.

• Anxiety with Hyperventilation: Air hunger. Classical complaint of not having enough air and not able to get sufficient air with inspiration. Multiple sighs during interview.

4. The diagnosis is congestive heart failure.   Speculate on the mechanism for the following historical information with the diagnosis of congestive heart failure

• Fatigue : poor perfusion 

• Anorexia. The loss of weight reflects the anorexia, possible problem with GI absorption and overall poor nutrition.

• Exertional dyspnea : By the time heart fails it has used up all its reserve capacity. Ability to increase cardiac output is limited.  Exertion demands the heart to increase cardiac output which it is unable to do, resulting in shortness of breath. (Specificity 60%)

• Paroxysmal nocturnal dyspnea 

  • Dreams

  • Slipping off of pillow

  • Sympathetic activity and phase of sleep

• Orthopnea. (Sensitivity 20-30%)

  • Increased venous return in supine position

  • Larger lung volume in upright position

  • Boggy congested liver pushing diaphragm up in supine position

  • Better use of accessory muscles in upright position

• Cough: productive of pink, frothy sputum  Encountered in pulmonary edema.

5. In terms of the pathophysiology, explain the mechanism for the following physical findings: 

Overall specificity of physical examination is 90% with a sensitivity of 10-30%

There are many data points in the physical examination which support the diagnosis. Comment on the 

• Patient’ appearance. The disheveled appearance of the patient may represent a combination of depression and inability to care for oneself because of cardiac failure, fatigue, etc. 

• The untied shoes most likely reflects the edema of the feet.

• Diaphoresis: Excess of sympathetic nervous system output

• Labored breathing – complex mechanism including peripheral receptors and modulation by nervous system Use of accessory muscles of respiration.

• Blue lips : Peripheral Cyanosis – poor peripheral circulation

• Cold hands: poor peripheral circulation

• Lowered BP – decreased stroke volume, pulse pressure is less than 30mmHg – primarily systolic pressure drop

• Distended neck veins – right heart failure with elevated right atrial pressure. The veins are pulsatile.

• Diminished S1 and S2 – high end diastolic pressure (A-V valves), decreased stroke volume (semilunar valves); dampening effect of pleural/pericardial effusions.

• Holosytolic murmur: The left ventricle is dilated (failure – high end diastolic volume). At the same time, the annulus of the atrio-ventricular valve is dilated. 

• S3: A third heart sound most likely represents a change in the compliance of the ventricular wall and vibrations set up when a column of blood enters a chamber with a high end diastolic pressure. Gallop sound.

• Tachycardia:

•  Irregular, irregular pulse: Atrial fibrillation. High pressure in the atrium leads to stretching the muscular wall – dilatation of the chamber – which induces a conduction abnormality.

• Pulsus alternans:  Alternating weak and strong pulse indicative of depressed LV function

• Palpable liver edge – passive congestion of the liver, right heart failure

• Pitting edema – elevated capillary hydrostatic pressure, passive venous congestion, right heart failure 

• Basal crackles:  Due to basal congestion of lungs the alveoli are atelectatic. They create a popping noise as they open at the end of inspiration.

• Dullness in bases of lung fields: If there is pleural effusion there will be impaired note to percussion.

6. Correlate (explain) the laboratory data in terms of the diagnosis.

• Although the hemoglobin is normal, the hematocrit is slightly low, reflecting the dilusional effect of water retention.

• Define azotemia and to explain what is meant by prerenal azotemia. Renal perfusion is poor in CHF leading to reduced urea clearance.

• Bilirubin, especially the indirect fraction, and enzymes, like alkaline phosphatase, may be elevated. Total protein may decline at the expense of the albumin produced in the liver. Hepatic congestion leads to hypoxia and altered function of the liver cells. 

• The electrolytes changes, especially hyponatremia, reflect a dilutional effect with water retention and decreased glomerular filtration rate (poor perfusion).

• Specific gravity is elevated with oliguria and water retention. Some protein escapes into the urine; hyaline casts are non-specific protein casts.

• Correlate the results of the chest x-ray (structural changes) with the clinical findings.

  • Cephalization of vasculature

  • Prominence of the vascular shadows – congestion of the pulmonary vessels from the hilus to the peripheral lung. Elevated vascular pressure.

  • Kerley lines: Interstitial edema, Increased lymphatic flow.

  • Butterfly pattern in pulmonary edema.

  • Pleural effusions – elevated hydrostatic pressure in the microscopic vessels of the pleural membranes. Effusions are clear, yellow liquid. Transudates. Often bilateral.

  • Increased cardiac diameter:  Cardiothoracic ratio >50%, dilated ventricles, pericardial effusion

7. What additional investigations are useful?

EKG: None specific for CHF. Useful to diagnose Cardiac ischemia, MI, Dysrhythmias, Ventricular hypertrophy, Electrolyte abnormalities, Dig toxicity etc.

Echocardiography: Helps in identification of regional wall motion abnormalities, left ventricular function, cardiac tamponade, valvular heart disease.

Radionuclide Ventriculography: Ejection fraction, chamber size and regional wall motion abnormalities.

Swna-Ganz catheter: LV filling pressure, Cardiac output In seriously ill patient with pulmonary edema.

8. What are compensatory attempts of the body to support failing heart: Which of these attempts are evident in Mr. Solomon?

Increased sympathetic nervous system output: 

• Compensatory: Positive chronotropic and Ionotropic effect. Sympathetic venoconstriction decreases capacitance of venous system and increase venous return to heart.

• Decompensatory: Excess is deleterious: Increasing myocardial oxygen requirement, increasing peripheral vascular resistance.

Starling curve shifts: Heart attempts to compensate for low cardiac output either by dilatation (to increase end diastolic pressure) or hypertrophy  (increased oxygen demand). The Starling curve is shifted downward to right and has a flattened contour in the patient with decreased cardiac contractility. Compliance refers to pressure required to fill ventricle to a certain volume. In CHF the ventricles become stiff (Non-compliant) requiring a higher LVEDP to achieve diastolic filling adequate to maintain cardiac output.

Rennin angiotensin system: Decreased renal perfusion leads to salt and water retention. Elevation of LVEDP.

9. Which of the following drugs given intravenously would you expect to result in a rapid improvement in Mr. Solomon’s clinical condition? Which drugs would be expected to increase urine output?

Inoptropic action resulting in increased cardiac output

• Amrinone, dobutamine, dopamine and digoxin are all positive inotropes that should lead to an improvement in Mr. Solomon’s clinical condition.

•  By increasing cardiac output, these drugs should increase renal blood flow resulting in some degree of diuresis. 

• Three of the drugs increase cAMP in cardiac muscle cells: amrinone by inhibiting phosphodiesterase; dobutamine and dopamine by stimulating beta-adrenergic receptors. 

• The onset of the inotropic action of these drugs should be immediate. 

• Digoxin inhibits the Na+ - K+ ATPase and increases Ca++ in the cardiac cell by inhibiting Na+ - Ca++ exchange. This drug should have a slower onset of action than the other inotropes. 

• Isoproterenol and norepinephrine are also inotropic drugs, but these agents are more likely to aggravate heart failure. Isoproterenol would cause sinus tachycardia while norepiniephrine would cause an alpha-mediated peripheral vasoconstriction. 

Heart failure would also be aggravated by verapmil and esmolol. 

Since the vagal tone would be low, atropine would have little effect. 

To decrease pre-load

• furosemide acts as a loop diuretic as well as a venodilator when given acutely and can cause prompt decrease in pulmonary edema. 

• Likewise, venodilation with nitroglycerine should decrease venous filling pressure and decrease capillary hydrostatic pressure and edema formation. 

• Venesection and rotating tourniquet are of historic significance.

Measure to decrease after load

Nitroprusside is an arteriolar dilator as well as venodilator. This drug should improve cardiac output (reduced after load) as well as reducing venous pressure and capillary hydrostatic pressure.

10. Explain normal Starling curve

11. Compared to normal, how do you think Mr. Solomon’s illness has altered his ventricular function curve (the relationship between LV end-diastolic and cardiac output)? Would his ventricular function curve be further altered by either digoxin, vasodilator therapy or diuretic therapy?

In CHF the ventricular function curve is shifted downward and to the right. Also the slope of the ascending portion of the curve is less steep. Both digoxin and vasodilator therapy would shift the function curve upward and to the left (but not back to normal).

 Diuretic therapy should not alter the curve, but should shift the operating point on the curve to the left. (towards decreased end-diastolic pressure).

12. What would be the most important concern in treating Mr. Solomon with a combination of digoxin and furosemide?

Furosemide (loop diuretic) causes increased excretion of both potassium and magnesium. Hypokalemia and hypomagnesemia will both increase the risk of digoxin-induced arrhythmias.

13. How should Mr. Solomon’s daily dose of digoxin be adjusted depending on his serum creatinine levels?

Since digoxin is secreted by the renal tubules; a reduction in renal blood flow will decrease the clearance of digoxin and leads to higher serum levels. Therapeutic digoxin concentration range from 1-2ng/ml. Toxicity appears at 2.5ng/ml. Creatinine is also secreted by the renal tubules and a rise in serum creatinine above 3.0mg/dL indicates reduced renal blood flow and the dose of digoxin should be decreased (by 50%).

14. What would cause activation of the rennin-angiotensin system in Mr. Solomon and how would the administration of enalapril counteract those effects? Would enalapril lead to alterations in serum levels of any other peptide (in addition to Angiotensin II) that might have cardiovascular effects.

Reduced perfusion pressure at the end of the afferent arterioles in the renal glomerulus (intrarenal baroreceptor) would cause increased rennin release. In addition, elevated sympathetic tone would cause increased rennin release. The rise in rennin should cause a concomitant rise in angiotensin II and aldosterone. The increase in A II would cause more arteriolar vasoconstriction, venoconstriction and increased salt and water retention by the kidneys. Enalapril would attenuate some of these effects by blocking the enzyme the enzyme that converts A I and A II. Since ACE also degrades bradykinin, enalapril would cause increased bradykinin levels which may have beneficial vasodilating in CHF.

15. After 6 months of treatment with digoxin, furosemide and enalapril, Mr. Solomon’s edema has resolved, but he continues to feel week and lethargic. Upon readmission to the hospital a catheter is placed into the right heart through a jugular vein and the following pressures are recorded: RA=6mmHg; PA-40/12mmHg; Wedge (mean)=12mmHg; cardiac output=3.5L/min. How should Mr. Solomon’s drug therapy be altered?

Since the chronically failing left ventricle usually requires high filling (wedge) pressures to achieve maximum stroke output, it would appear that Mr. Solomon has had too much diuresis. The use of a ACE inhibitor enhances the diuretic action of furosemide. Appropriate treatment might be to switch to less potent diuretic (thiazide) and to carefully adjust the dosages of both diuretic and enalapril to increase end-diastolic filling pressure and improve cardiac output without causing the recurrence of edema.

16. What are the common etiologies for congestive heart failure? What is the most likely etiology of heart failure in Mr. Solomon?

• Ischemic heart disease

• Hypertension

• Valvular heart disease

• Cardiomyopathies

Mr. Solomon has Coronary artery disease. He has old Myocardial infarction

17. Let us summarize the therapeutic strategies to manage a patient in congestive heart failure?

Decrease metabolic need. Oxygen demand supply ratio: Bed rest, Oxygen, decrease catecholamine activity (Beta-blockers)

To reduce venous return (pre-load): Elevate head end of bed, Nitrates, Diuretics (Furosemide) (Old tricks: Alternating tourniquet, Phlebotomy)

Increase cardiac output: Inotropic agents:   dopamine, dobutamine, amrinone, milrinone, digoxin (chronic chf)  nitropress,

Reduce work load: Reduce after-load: , Peripheral vascular resistance. Arterial dilatation (Nitrates, nitropress) IABP

Underlying cause: Diastolic dysfunction (reduce blood pressure) Replacing stenotic valve.

Eliminate contributing factors: Anemia

Counter deleterious compensatory efforts:  Rennin agiotensin system. Salt and water restriction, ACE inhibitors (Captopril, Enalpril)

Analgesics and Anxiolytic: Morphine (Pulmonary edema) 

Cardiac Transplantation: Last resort to a completely failed Heart refractory to therapy.

Mechanical ventilation: In severe cases of pulmonary edema. To support ventilation. Provide rest to Myocardium. To control pulmonary edema.

Dialysis: Combined Renal and Heart failure

18 Let us understand few commonly used terms in relationship to Heart failure.

• LV failure:

  • LV dysfunction

  • Low cardiac output

  • Pulmonary vascular congestion

• RV failure

  • RV dysfunction

  • Systemic venous congestion

• Corpulmonale: Right heart failure secondary to Lung disease

• Low output failure: Normal metabolic requirements not met

• High output failure: Elevated circulatory demands not met

• Forward failure: Fatigue, Weakness, Azotemia

• Backward failure: Pulmonary and systemic venous congestion

• Acute Heart failure

• Flash Pulmonary edema

• Chronic Heart failure

19. Let us recall some of the concepts we learned in Function course and apply to our patient.

• Venous return

• Venous tone

• End diastolic pressure

• Stroke volume

• Heart rate

• Cardiac output

• Starling Curve

• Peripheral vascular resistance

• Autonomic nervous system regulation of CVS

• Wedge pressure

• Intravascular volume