Cardiology: CHF Board Review Course

Contents
CHF Board Exam Review
CHF Exam Review

A compilation of material from:

1. Online sources

2. CHF Board Review Course

3. JHLTHeart failure -- Epidemiology

POINTS:

OUTCOMES

1. Relative improvement in survival over time
2. 50% 5 year mortality
3. Mortality worse as age increases
4. Mortality worse in black men

   ALVD

1. Patients with ALVD have half the mortality of HF patients (5% per year annualized)
2. Risk of death 5X - 8X that of normal age-matched population
3. SOLVD Prevention trial
a. HF developed in 10% untreated ALVD patients per year
b. Further 8% annual risk of death or hospitalization

   MAJOR RISK FACTORS

1. Age, male sex
2. Hypertension, LVH
3. Myocardial infarction
4. Diabetes mellitus
5. Valvular heart disease
6. Obesity

   3 DON'T DOs

1. Don't give Digoxin to patients in NSR with low EF but no hx HF
2. Don't give Diltiazem or Verapamil to patients with low EF but no sx CHF
3. Don't Give nutritional supplements to treat structural heart disease or HF
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Beta-blockers do not improve O2 consumption

The lower the BP, the higher the mortality

The lower the MLHF scores, the better the survival

The higher the KCCQ score, the better the patient's functional capacity. KCCQ scores do not predict prognosis.

Heart failure -- Pathophysiology
Calcium handling

With cell depolarization, Ca2+ enters the cell through the voltage dependent calcium channels (blocked by ca2+ channel antagonists)
Ca2+ activates Ryanodine receptor, the major calcium release channel of the sarcoplasmic reticulum (major storage pol for Ca2+ in cardiac myocytes)
Ca2+ is released, resulting in contraction
Cardiac relaxation occurs when Ca2+ is removed from the cytosol by being taken up by the sarcoplasmic reticulum Ca2+-ATPase (SERCA2a)
Several abnormalities:
decrease in how much SERCA2a is available -- leading to impaired re-uptake of Ca2+, and abnormal relaxation
Cytosol depleted of Ca2+, insufficient Ca2+ is released during systole
Increased sympathetic tome may de-inhibit the Ryanodine receptor, leading to excess diastolic leak of Ca2+. With pre-existing increased diastolic Ca2+ from dysfunctional SERCA2a, can lead to after depolarizations producing VEs

Heart failure -- Pathophysiology -- PV loops
CV Physiology: Ventricular Pressure-Volume Relationship

CV Physiology: Effects of Preload, Afterload and Inotropy on Ventricular Pressure-Volume Loops

Laplace law:

T = ( P * R ) / M

Heart failure -- Asymptomatic LVD
Recommendations

5.1 It is recommended that all patients with ALVD exercise
regularly according to a physician-directed
prescription to avoid general deconditioning; to optimize
weight, blood pressure, and diabetes control;
and to reduce cardiovascular risk. (Strength of
Evidence 5 C)

5.2 Smoking cessation is recommended in all patients including
those with ALVD. (Strength of Evidence B)
5.3 Alcohol abstinence is recommended if there is current
or previous history of excessive alcohol intake.
(Strength of Evidence 5 C)
5.4 It is recommended that all patients with ALVD
with hypertension achieve optimal blood pressure
control. (Strength of Evidence 5 B)

5.5 ACE inhibitor therapy is recommended for asymptomatic
patients with reduced LVEF (!40%).
(Strength of Evidence 5 A)

5.6 ARBs are recommended for asymptomatic patients
with reduced LVEF who are intolerant of ACE inhibitors
from cough or angioedema. (Strength of Evidence C)

Routine use of the combination of ACE inhibitors and ARBs for prevention of HF is not recommended in this population. (Strength of Evidence 5 C)

5.7 Beta blocker therapy should be considered in asymptomatic
patients with reduced LVEF. (post-MI,
Strength of Evidence 5 B; non post-MI, Strength of
Evidence 5 C)

Heart failure -- Prevention

Recommendation

3.3 ACE inhibitors are recommended for prevention of
HF in patients at high risk of this syndrome, including
those with coronary artery disease, peripheral
vascular disease, or stroke. Patients with
diabetes and another major risk factor or patients
with diabetes who smoke or have microalbuminuria
are also at high risk and should receive ACE
inhibitors. (Strength of Evidence 5 A)

3.4 Beta blockers are recommended for patients with
prior MI to reduce mortality, recurrent MI, and
the development of HF. (Strength of Evidence 5 A)

Heart failure -- Initial Assessment Class I
INITIAL ASSESSMENT

1. A thorough history and physical examination should be obtained/performed in patients presenting with HF to identify cardiac and noncardiac disorders or behaviors that might cause or accelerate the development or progression of HF. (Level of Evidence: C)

2. A careful history of current and past use of alcohol, illicit drugs, current or past standard or "alternative therapies,'' and chemotherapy drugs should be obtained from patients presenting with HF. (Level of Evidence: C)

3. In patients presenting with HF, initial assessment should be made of the patient's ability to perform routine and desired activities of daily living. (Level of Evidence: C)

4. Initial examination of patients presenting with HF should include assessment of the patient's volume status, orthostatic blood pressure changes, measurement of weight and height, and calculation of body mass index. (Level of Evidence: C)

5. Initial laboratory evaluation of patients presenting with HF should include complete blood count, urinalysis, serum electrolytes (including calcium and magnesium), blood urea nitrogen, serum creatinine, fasting blood glucose (glycohemoglobin), lipid profile, liver function tests, and thyroid-stimulating hormone. (Level of Evidence: C)

6. Twelve-lead electrocardiogram and chest radiograph (PA and lateral) should be performed initially in all patients presenting with HF. (Level of Evidence: C)

7. Two-dimensional echocardiography with Doppler should be performed during initial evaluation of patients presenting with HF to assess LVEF, left ventricular size, wall thickness, and valve function. Radionuclide ventriculography can be performed to assess LVEF and volumes. (Level of Evidence: C)

8. Coronary arteriography should be performed in patients presenting with HF who have angina or significant ischemia unless the patient is not eligible for revascularization of any kind (4--8). (Level of Evidence: B)

Heart failure -- Initial Assessment Class II

1. Coronary arteriography is reasonable for patients presenting with HF who have chest pain that may or may not be of cardiac origin who have not had evaluation of their coronary anatomy and who have no contraindications to coronary revascularization. (Level of Evidence: C)

2. Coronary arteriography is reasonable for patients presenting with HF who have known or suspected coronary artery disease but who do not have angina unless the patient is not eligible for revascularization of any kind. (Level of Evidence: C)

3. Noninvasive imaging to detect myocardial ischemia and viability is reasonable in patients presenting with HF who have known coronary artery disease and no angina unless the patient is not eligible for revascularization of any kind (9). (Level of Evidence: B)

4. Maximal exercise testing with or without measurement of respiratory gas exchange and/or blood oxygen saturation is reasonable in patients presenting with HF to help determine whether HF is the cause of exercise limitation when the contribution of HF is uncertain. (Level of Evidence: C)

5. Maximal exercise testing with measurement of respiratory gas exchange is reasonable to identify high- risk patients presenting with HF who are candidates for cardiac transplantation or other advanced treatments (10--12). (Level of Evidence: B)

6. Screening for hemochromatosis, sleep-disturbed breathing, or human immunodeficiency virus is reasonable in selected patients who present with HF. (Level of Evidence: C)

7. Diagnostic tests for rheumatologic diseases, amyloidosis, or pheochromocytoma are reasonable in patients presenting with HF in whom there is a clinical suspicion of these diseases. (Level of Evidence: C)

8. Endomyocardial biopsy can be useful in patients presenting with HF when a specific diagnosis is suspected that would influence therapy (13). (Level of Evidence: C)

9. Measurement of natriuretic peptides (BNP and NT- proBNP) can be useful in the evaluation of patients presenting in the urgent care setting in whom the clinical diagnosis of HF is uncertain. Measurement of natriuretic peptides (BNP and NT-proBNP) can be useful in risk stratification (14--21). (Level of Evidence: A)

Heart failure -- Initial Assessment Class III

INITIAL ASSESSMENT

1. Endomyocardial biopsy should not be performed in the routine evaluation of patients with HF (13). (Level of Evidence: C)

2. Routine use of signal-averaged electrocardiography is not recommended for the evaluation of patients presenting with HF. (Level of Evidence: C)

3. Routine measurement of circulating levels of neurohormones (e.g., norepinephrine or endothelin) is not recommended for patients presenting with HF. (Level of Evidence: C)

Heart failure -- Biomarkers

A. BNP as a screening tool

BNP does not work for screening b/o low disease prevalence
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B. NTproBNP vs. BNP

1. NTproBNP values are between 5 X and 10X BNP levels

2. Both affected by age but NTproBNP is more so

3. Both are affected by renal function but NTproBNP is more so

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C. False positives and negatives

1. False negatives:

a. Obesity
b. Acute MR
c. Flash pulmonary edema

2. False positives

a. Renal dysfunction
b. Pulmonary embolus/pulm. HTN
c. rapid lowering of PCWP
d. ACS
e. Age/sex

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D. Practical Approach to BNP in ER

1. BNP < 100 --- HF unlikely (NPV 90%)

2. BNP > 500 --- HF likely (PPV 90%)

3. Between 100 and 500, values fall into a "grey zone."
Consider other diagnosis such as PE, cor pulmonale
Baseline values helpful in these instances

Heart failure -- Assessment -- CPXT 1

A. Measuring AT using Ventilatory equivalents

(see attached diagram)

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B. 6MWT vs. CPXT

1. 6MWT is a better estimate of patient's actual functional level

2. 6MWT is a measurement of submaximal exercise capacity

3. Does not measure VO2

4. Does not diagnose cause of DOE

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C. Cardiopulmonary Exercise Testing -- Initial Assessment

"NOT recommended in the routine initial evaluation"

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D. Cardiopulmonary Exercise testing -- definitions

1. PkVO2: Highest VO2 achieved, generally occurs near peak exercise

2. Maximal O2 uptake: Value achieved when O2 remains stable despite a progressive increase in exercise intensity. Synonymous with peak aerobic capacity

3. Breathing reserve: Reserve capacity of ventilatory system

Equals 1- {peak exercise minute ventilation}/{maximal voluntary ventilation}

A normal value is 0.3 (30%)

4. Anaerobic threshold: Highest oxygen uptake attained without a sustained increase in blood lactate concentration and lactate/pyruvate ratio Reported as ml/kg/min

5. Respiratory exchange ratio (RER): Related but not equivalent to its cellular counterpart, the respiratory quotient, and is defined as the ratio of V ̇CO2 to V ̇O2

6. Ventilation/carbon dioxide production ratio (V ̇ E/V ̇ CO2): Also known as the ventilatory equivalent for CO2, this represents a respiratory control function that reflects chemoreceptor sensitivity, acid-base balance, and ventilatory efficiency

Rules of thumb

1. A peak oxygen uptake(PkVO2) < 85% of that predicted by age and gender is considered to be low

2. A normal anaerobic threshold (AT) is generally closer to 60% of the predicted PkV ̇ O2.

3. An AT < 40% of the predicted peak V ̇ O2 is considered pathologically reduced and indicative of circulatory insufficiency

4. A breathing reserve (BR) < 30% would indicate ventilatory impairment, especially when accompanied by oxygen desaturation with exercise, although a BR of 20% to 30% is deemed a borderline value

5. A respiratory exchange ratio (RER) of < 1.1 (particularly < 1.0) in the absence of other metabolic abnormalities suggests poor effort, anxiety, or mild disease.

6. When RER < 1.05, use VE/VCO2 slope > 35 as a guide to listing

7. In obese patients (BMI > 30) adjust Pk VO2 lean body mass (Pk VO2 < 19 ml/min/kg).

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E. Reasons to perform Cardiopulmonary Exercise Testing

1. Eval. for exertional dyspnea

2. Develop an exercise prescription

3. Measure peak VO2

4. Risk stratify and assess prognosis in HF

5. Assess impairment for disability

6. assess functional significance of regurgitant valvular disease

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Heart failure -- Assessment -- CPXT 2 (pdf files)

Heart failure -- Assessment -- CPXT 3 (pdf files)

Heart failure -- Assessment -- CPXT 4 (pdf files)

Heart failure -- Assessment -- EMB -- general

Heart failure -- Assessment -- EMB -- Class I, Class II, Class III
Class 1

New onset HF < 2 weeks duration

- normal sized or dilated LV
- hemodynamic compromise

New onset HF 2 - 12 weeks duration

- new ventricular arrhythmias
- Advanced AV block
- Failure to respond to usual Rx within 1 - 2 weeks

Class 2

- Failure to respond to usual Rx

- Search for myocarditis or SPECIFIC Dx
- rash, eosinophilia
- Severe HF, normal EF, no HTN
- Systemic features (hilar adenopathy)
- Autoimmune features

- Unexplained ventricular arrhythmias

Class 3

Not indicated as part of the routine eval. of HF

Heart failure -- Assessment -- EMB (pdf)

Heart failure -- Cardiorenal syndrome

CARDIORENAL SYNDROME

a) No correlation between baseline creatinine or GFR and PCW, CI, or SVR

b) Weak correlation between creatinine and RAP (R = 0.165, p =0.03)

c) No correlation between RAP, PCW, CI, SVR and worsening renal function

d) No correlation between changes in hemodynamic parameters and worsening renal function

e) in ESCAPE, no difference between clinical assessment or Swan and GFR

Cardiorenal syndrome caused by impaired perfusion

•Ensure patient is not hypovolemic

•Clinical signs, echo parameters

•Withhold diuretics and give fluids

•Assess CO, SVR, SBP

•If SVR high, vasodilators are helpful

•If SBP < 80, and CI < 1.5, give inotropes, pressors or MCS

•Hypotension with worsening renal function is an absolute indication for pressor support

•SBP between 80 and 90 may have reduced renal function despite low normal CI - akin to septic shock ("warm" shock)

Cardiorenal syndrome caused by renal disease

•If volume, SBP and CO are all OK, cardiorenal syndrome is caused by renal disease

•Irreversible

•Avoid causing further renal damage

•Don’t perform needless IV contrast studies

•Don’t overdiurese

•Give IV infusions, not bolus doses

•Use combo diuretic Rx

•Consider ultrafiltration

Heart failure -- Co-morbidities

1. Sleep Related Breathing Disorder

50% HF patients have either sleep apnea or Cheyne-Stokes respiration

a) Sleep apnea

•central
- •increased mortality in CHF patients
- •does not correlate with LVEF

•obstructive: cessation of air flow > 10 sec with continued abdominal and chest effort
- •85% men
- •prevalence 2% in women, 4% in men
- •more than snoring and daytime somnolence: AM headache, poor job performance, personality change

b) Cheyne-Stokes respiration

•Commonest form of SDB in pts with severe LV dysfunction

c) CPAP

•Increases LVEF, decreases MR and improves QOL
•Does not reduce mortality

2. Obesity

•Obesity paradox: obesity increases risk for CHF but obese CHF patients do better than lean ones
•Adiponectin is a cytokine with antiatherogenic, anti-inflammatory and anti-diabetic properties
•Levels are higher in CHF patients but there is functional resistance

3. DM

•15% - 25% pts in CHF trials had DM
•25% - 30% hospitalized HF pts have DM
•In HF pts, DM is an independent risk factor for death
•DM Cardiomyopathy can have both ischemic and nonischemic contributions
•In diabetic HF pts thiazolidinediones and biguanides are contraindicated. Consider Byetta and Januvia

4. Anemia

•Do not use Erythrocyte stimulating agents to increase Hgb > 12

5. Anthracyclines

•Mechanism of toxicity may be from oxygen-free radicals
•Occurs with any dose
•Low incidence (< 1%) when cumulative dose < 550 mg/m2
•Occurs within a month to 1 year but also can occur years after. Responds to therapy, even if occurs late
•Dexrazoxane (Zinecard) may block production of O2-free radicals; protect heart muscle from Anthracycline cardiotoxicity

6. Trastuzumab (Herceptin)

•Monoclonal antibody to HER protein
•2% risk of cardiotoxicity if used alone, 16% when used with other agents

7. Depression

Heart failure -- Cardiac catheterization

A. Causes of a large V wave in PCW

1. MR

2. VSD

3. Nitric oxide inhalation -- this decreases PVR, leading to the left heart being flooded. In the setting of decreased LA compliance, this will raise the V wave

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B. CVP

1. Inspiratory fall of 2 - 3 mm Hg

2. Atrial events of "out of phase" from ventricular events

3. A wave -- early ventricular diastole
           Reflection of atrial contraction

4. X descent -- early ventricular systole
           Usually predominant in normal individuals

5. V wave -- late ventricular systole
           Determined by atrial compliance

6. Y descent -- Late ventricular diastole
           Determined by ventricular compliance

7. CVP X 2 = PCW

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C. Fick Cardiac Output Calculation

VO2 = CO X (Ca - Cv)

CO = VO2
        (Ca -Cv)

O2 content of blood is Hgb (g/dl) X 1.36 ml O2/gm Hgb X O2 sat + 0.0032 X pO2

(usually 0.0032 X pO2 can be ignored)



Cardiac Outputs can be increased theoretically by 18X:

   a) Ca - Cv can be increased 3X
   b) HR can be increased by 3X
   c) SV can be increaser 2X

For example:

VO2 = 125 ml/min
Arterial O2 sat 99%
Venous O2 sat 75%
BSA 2 sq. m

Cardiac output is:

                               125 X 2 (numerator) = 5.7 L/min (denominator)
(0.99 - 0.75) X Hgb (14) X 1.36 X 10 (dl/L)

CI is 2.85 L/min/sq. m.

Error in Fick calculation is up to 10%

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D. Hemodynamic-Guided therapy

VASODILATOR THERAPY

Hemodynamic Targets

1. PCW < 15 - 20 mm Hg

2. SVR < 1200 dynes-sec-cm^5

3. mRAP < 8 - 10 mm Hg

4. SBP > 80 mm Hg

Titration of oral vasodilators as nitroprusside weaned

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E. LVSWI

{MAP - PCW} X CI X 0.0136 gm-m (numerator)
                             HR X m^2               (denominator)

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F. RVSWI

{mPAP - CVP} X CI X 0.0136 gm-m (numerator)
                              HR X m^2                (denominator)

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G. PCW

1. At diastasis, in the absence of atrial or MV obstruction, PCW = LA = LVEDP

2. Pressure can be confirmed by measuring wedge sat or transseptal puncture. Sat should be > 95%

3. PAD < 3 mm Hg greater than LVEDP

4. V wave < 2 X A wave

5. Thoracic, not intracardiac, pressure

6. PCW X 2 = SPAP

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H. Shunt calculation

1. Any step-up of > 7% is abnormal

(see attached file)

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I. Vascular resistances

SVR 800 - 1200 dynes-sec-cm^5

PVR 80 - 120 dynes-sec-cm^5

Wood units = dynes-sec-cm^5/80

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Heart failure -- Cardiac catheterization (attached files)

Heart failure -- Cath (constriction, tamponade, restriction)

Clinical and Hemodynamic findings in Compressive Pericardial disease

Tamponade	Subacute constriction	Chronic constriction
Etiology	Idiopathic Neoplasm Traume	Idiopathic Uremic Radiation, malignancy Collagen vascular disease Infectious (TB)	Idiopathic Infectious (TB)
Pulsus paradoxus (> 0 mm Hg)	Marked	Moderate	Slight
RAP waveform	X, Xy	Xy, XY	XY, xY
LV - RV equilibration	Depends on which phase	+ _	+
RA = PCW	Depends on which phase	+ _	+
CXR pericardial Ca2+	__	+ _	+
Cardiomegaly	+	+ _	_

Hemodynamic Criteria for Restriction vs. Constriction

Constriction	Restriction
EDP equalization	LVEDP - RVEDP < 5	LVEDP - RVEDP > 5
PAP	PASP < 55	PASP > 55
High RVEDP	RVEDP > 1 RVSP 3	RVEDP < 1 RVSP 3
Dip plateau morphology	LV rapid filling wave > 7	LV rapid filling wave < 7
Kussmaul sign	Lack of normal respiratory variation in mean RAP	Normal respiratory variation in mean RAP

Heart Failure -- Therapy Class I
Class 1

1. Measures listed as Class I recommendations for patients in stages A and B are also appropriate for patients in Stage C. (Levels of Evidence: A, B, and C as appropriate)

2. Diuretics and salt restriction are indicated in patients with current or prior symptoms of HF and reduced LVEF who have evidence of fluid retention (see Table 4 in the full-text guidelines). (Level of Evidence: C)

3. Angiotensin-converting enzyme inhibitors are recommended for all patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated (see text, Table 3 in the full-text guidelines) (41--53). (Level of Evidence: A)

4. Beta blockers (using 1 of the 3 proven to reduce mortality, i.e., bisoprolol, carvedilol, and sustained release metoprolol succinate) are recommended for all stable patients with current or prior symptoms of HF and reduced LVEF, unless contraindicated (see text, Table 3 in the full-text guidelines) (54--72). (Level of Evidence: A)

5. Angiotensin II receptor blockers (see Table 3 in the full- text guidelines) are recommended in patients with current or prior symptoms of HF and reduced LVEF who are ACE inhibitor-intolerant (see text for information regarding patients with angioedema) (73--83). (Level of Evidence: A)

6. Drugs known to adversely affect the clinical status of patients with current or prior symptoms of HF and reduced LVEF should be avoided or withdrawn whenever possible (e.g., nonsteroidal anti-inflammatory drugs, most antiarrhythmic drugs, and most calcium channel blocking drugs; see text) (84--90). (Level of Evidence: B)

7. Exercise training is beneficial as an adjunctive approach to improve clinical status in ambulatory patients with current or prior symptoms of HF and reduced LVEF (90a--90d). (Level of Evidence: B)

8. An implantable cardioverter-defibrillator is recommended as secondary prevention to prolong survival in patients with current or prior symptoms of HF and reduced LVEF who have a history of cardiac arrest, ventricular fibrillation, or hemodynamically destabilizing ventricular tachycardia (91--93). (Level of Evidence: A)

9. Implantable cardioverter-defibrillator therapy is recommended for primary prevention of sudden cardiac death to reduce total mortality in patients with non-ischemic dilated cardiomyopathy or ischemic heart disease at least 40 days post-MI, a LVEF less than or equal to 35%, and NYHA functional class II or III symptoms while receiving chronic optimal medical therapy, and who have reasonable expectation of survival with a good functional status for more than 1 year (40,93--99). (Level of Evidence: A)

10. Patients with LVEF of less than or equal to 35%, sinus rhythm, and NYHA functional class III or ambulatory class IV symptoms despite recommended, optimal medical therapy and who have cardiac dyssynchrony, which is currently defined as a QRS duration greater than or equal to 0.12 seconds, should receive cardiac resynchronization therapy, with or without an ICD, unless contraindicated (100--115). (Level of Evidence: A)

11. Addition of an aldosterone antagonist is recommended in selected patients with moderately severe to severe symptoms of HF and reduced LVEF who can be carefully monitored for preserved renal function and normal potassium concentration. Creatinine should be 2.5 mg per dL or less in men or 2.0 mg per dL or less in women and potassium should be less than 5.0 mEq per liter. Under circumstances where monitoring for hyperkalemia or renal dysfunction is not anticipated to be feasible, the risks may outweigh the benefits of aldosterone antagonists (116--118). (Level of Evidence: B)

12. The combination of hydralazine and nitrates is recommended to improve outcomes for patients self- described as African-Americans, with moderate-severe symptoms on optimal therapy with ACE inhibitors, beta blockers, and diuretics (119,120). (Level of Evidence: B)

Heart Failure -- Therapy Class II
Class IIa

1. It is reasonable to treat patients with atrial fibrillation and HF with a strategy to maintain sinus rhythm or with a strategy to control ventricular rate alone (121-- 125). (Level of Evidence: A)

2. Maximal exercise testing with or without measurement of respiratory gas exchange is reasonable to facilitate prescription of an appropriate exercise program for patients presenting with HF. (Level of Evidence: C)

3. Angiotensin II receptor blockers are reasonable to use as alternatives to ACE inhibitors as first-line therapy for patients with mild to moderate HF and reduced LVEF, especially for patients already taking ARBs for other indications (73--82). (Level of Evidence: A)

4. Digitalis can be beneficial in patients with current or prior symptoms of HF and reduced LVEF to decrease hospitalizations for HF (126--133). (Level of Evidence: B)

5. The addition of a combination of hydralazine and a nitrate is reasonable for patients with reduced LVEF who are already taking an ACE inhibitor and beta blocker for symptomatic HF and who have persistent symptoms (119,134). (Level of Evidence: B)

6. For patients who have LVEF less than or equal to 35%, a QRS duration of greater than or equal to 0.12 seconds, and atrial fibrillation (AF), CRT with or without an ICD is reasonable for the treatment of NYHA functional class III or ambulatory class IV heart failure symptoms on optimal recommended medical therapy (3,135). (Level of Evidence: B)

7. For patients with LVEF of less than or equal to 35% with NYHA functional class III or ambulatory class IV symptoms who are receiving optimal recommended medical therapy and who have frequent dependence on ventricular pacing, CRT is reasonable (3). (Level of Evidence: C)

Class IIb

1. A combination of hydralazine and a nitrate might be reasonable in patients with current or prior symptoms of HF and reduced LVEF who cannot be given an ACE inhibitor or ARB because of drug intolerance, hypotension, or renal insufficiency (119,136,137). (Level of Evidence: C)

2. The addition of an ARB may be considered in persistently symptomatic patients with reduced LVEF who are already being treated with conventional therapy (73--82). (Level of Evidence: B)

Heart Failure -- Therapy Class III
Class 3

1. Routine combined use of an ACE inhibitor, ARB, and aldosterone antagonist is not recommended for patients with current or prior symptoms of HF and reduced LVEF. (Level of Evidence: C)

2. Calcium channel blocking drugs are not indicated as routine treatment for HF in patients with current or prior symptoms of HF and reduced LVEF (138--141). (Level of Evidence: A)

3. Long-term use of an infusion of a positive inotropic drug may be harmful and is not recommended for patients with current or prior symptoms of HF and reduced LVEF, except as palliation for patients with end-stage disease who cannot be stabilized with standard medical treatment (see recommendations for Stage D). (Level of Evidence: C)

4. Use of nutritional supplements as treatment for HF is not indicated in patients with current or prior symptoms of HF and reduced LVEF

5. Hormonal therapies other than to replete deficiencies are not recommended and may be harmful to patients with HF and reduced LVEF

Heart failure -- B-blockers (general)

Beta-adrenergic blockers in CHF

•Absolute contraindications

•Steroid-dependent asthma
•Sinus node disease, 2nd/3rd degree HB

•Relative contraindications

•Depression
•PVD with rest pain
•Brittle diabetes with recurrent hypoglycemia
•First degree HB with PR > 0.24
•Vasospastic angina
•Resting HR < 55
•SBP < 80

•Criteria to start BB in CHF

•Chronic stable HF

•No contraindications
•No volume overload
•No symptomatic hypotension
•No worsening renal or hepatic function
•Stable doses of diuretics and ACE-I

•ADHF

•All criteria for CSHF + Clinically stable for 24 - 48 hrs off inotropic Rx

Heart failure -- B-blockers (worsened HF)

Clinical	Suggested Rx	BB dose	BB dose uptitration
Wet/warm	1. Diuretics 2. Increase vasodilators if BP permits	Continue current dose	Only after congestion resolved and pt stable
Wet/cold	1. Diuretics 2. Adjust vasodilators until perfusion OK	1. Hold/reduce until perfusion OK 2. Restart BB at lower dose	Modify dosing schedule
Dry/cold	1. Hold diuretics if obviously volume depleted 2. Adjust vasodilators until perfusion OK 3. Inotropes?	1. Hold/reduce until Perfusion OK 2. Restart BB at lower dose	Modify dosing schedule

Heart failure -- with preserved LVEF (pdf)

Heart failure -- with preserved LVEF
11.5 Diuretic treatment is recommended in all patients
with HF and clinical evidence of volume overload,
including those with preserved LVEF. Treatment
may begin with either a thiazide or loop diuretic

11.6 In the absence of other specific indications for these
drugs, angiotensin receptor blockers (ARBs) or angiotensin
converting enzyme (ACE) inhibitors may
be considered in patients with HF and preserved
LVEF

11.7 ACE inhibitors should be considered in all patients
with HF and preserved LVEF who have symptomatic
atherosclerotic cardiovascular disease or diabetes
and one additional risk factor. (Strength of
Evidence 5 C)
In patients who meet these criteria but are intolerant
to ACE inhibitors, ARBs should be considered.

11.8 Beta blocker treatment is recommended in patients
with HF and preserved LVEF who have:

Prior myocardial infarction
Hypertension
Atrial fibrillation requiring control of ventricular rate

11.9 Calcium channel blockers should be considered inpatients with HF and preserved LVEF and:

Atrial fibrillation requiring control of ventricular rate and intolerance to beta blockers. In these patients, diltiazem or verapamil should be considered.
Hypertension

ADHF -- atrial fibrillation.pdf ADHF -- atrial fibrillation

Atrial fibrillation

•A common rhythm in patients with acute decompensated heart failure (ADHF)
•20% to 35% of patients with ADHF who are admitted to the hospital will be in AF at presentation
•In about one third of these patients, the AF will be of recent onset

5 questions to ask before Rx

•Does the patient have an ICD or pacemaker in place?
•Does the patient have preserved or reduced systolic function at their baseline?
•What is the duration of the AF episode?
•Is the patient already on drugs for rhythm or rate control and anticoagulation?
•What concomitant disorders are present?

Rate control vs. rhythm control 3 scenarios for a. fib. and ADHF

•Pts present shortly after onset of a. fib. with ADHF
- •Rhythm control often feasible
•Pts unaware of a. fib. and present with ADHF weeks to mos. after onset
- •Rhythm control sometimes feasible
•Pts chronically in a. fib. present with ADHF
- •Rhythm control usually not feasible

Rules of thumb

•In pts with a. fib. and ADHF, immediate cardioversion should rarely be the first step, b/c recurrence rate in still-decompensated pts is very high
•Rate control is the preferred initial strategy
•Although ideal rate is < 100, this is often not feasible
•Rate < 120 after a few hours is a reasonable goal
•Diltiazem has a place only if LV systolic function known to be normal
•Digoxin should be first-line agent considered, but may have a limited effect in pts with high sympathetic tone Small doses of IV beta-blocker can be cautiously given

•Rate control, along with volume correction and relief of dyspnea, may result in spontaneous restoration if NSR
•IV Amiodarone can be added if patient not already on an antiarrhythmic that prolongs QT like Dofetilide or Sotalol

ADHF -- Hemodynamic Monitoring Acute Heart Failure

When is hemodynamic monitoring justified?

Class 1

To guide therapy in patients in respiratory distress or impaired perfusion when cardiac filling pressures cannot be estimated clinically

Class IIa

Unclear hemodynamic status

Relative hypotension

Cardiorenal syndrome

When inotropic Rx considered

Consideration for advanced therapies

Class 3

Routine use of hemodynamic monitoring in patients with ADHF and symptomatic response to diuretics and vasodilators is NOT recommended

ADHF -- Dx & Therapy -- Class I Class 1

1. The diagnosis of HF is primarily based on signs and symptoms derived from a thorough history and physical examination. Clinicians should determine the following:

a adequacy of systemic perfusion;
b volume status;
c the contribution of precipitating factors and/or comorbidities;
d if the heart failure is new onset or an exacerbation of chronic disease; and
e whether it is associated with preserved ejection fraction.

Chest radiographs, electrocardiogram, and echocardiography are key tests in this assessment. (Level of Evidence: C)

2. Concentrations of B-type natriuretic peptide (BNP) or N-terminal pro-B-type natriuretic peptide (NT-proBNP) should be measured in patients being evaluated for dyspnea in which the contribution of HF is not known. Final diagnosis requires interpreting these results in the context of all available clinical data and ought not to be considered a stand-alone test (565,566). (Level of Evidence: A)

3. Acute coronary syndrome precipitating HF hospitalization should be promptly identified by electrocardiogram and cardiac troponin testing, and treated as appropriate to the overall condition and prognosis of the patient. (Level of Evidence: C)

4. It is recommended that the following common potential precipitating factors for acute HF be identified as recognition of these comorbidities is critical to guide therapy:

a acute coronary syndromes/coronary ischemia;
b severe hypertension;
c atrial and ventricular arrhythmias;
d infections;
e pulmonary emboli;
f renal failure; and
g medical or dietary noncompliance. (Level of Evidence: C)

5. Oxygen therapy should be administered to relieve symptoms related to hypoxemia. (Level of Evidence: C)

6. Whether the diagnosis of HF is new or chronic, patients who present with rapid decompensation and hypoperfusion associated with decreasing urine output and other manifestations of shock are critically ill and rapid intervention should be used to improve systemic perfusion. (Level of Evidence: C)

7. Patients admitted with HF and with evidence of significant fluid overload should be treated with intravenous loop diuretics. Therapy should begin in the emergency department or outpatient clinic without delay, as early intervention may be associated with better outcomes for patients hospitalized with decompensated HF (32,567,568). (Level of Evidence: B) If patients are already receiving loop diuretic therapy, the initial intravenous dose should equal or exceed their chronic oral daily dose. Urine output and signs and symptoms of congestion should be serially assessed, and diuretic dose should be titrated accordingly to relieve symptoms and to reduce extracellular fluid volume excess. (Level of Evidence: C)

8. Effect of HF treatment should be monitored with careful measurement of fluid intake and output; vital signs; body weight, determined at the same time each day; clinical signs (supine and standing) and symptoms of systemic perfusion and congestion. Daily serum electrolytes, urea nitrogen, and creatinine concentrations should be measured during the use of IV diuretics or active titration of HF medications. (Level of Evidence: C)

9. When diuresis is inadequate to relieve congestion, as evidenced by clinical evaluation, the diuretic regimen should be intensified using either:

a higher doses of loop diuretics;
b addition of a second diuretic (such as metolazone, spironolactone, or intravenous chlorothiazide); or
c continuous infusion of a loop diuretic. (Level of Evidence: C)

10. In patients with clinical evidence of hypotension associated with hypoperfusion and obvious evidence of elevated cardiac filling pressures (e.g., elevated jugular venous pressure; elevated pulmonary artery wedge pressure), intravenous inotropic or vasopressor drugs should be administered to maintain systemic perfusion and preserve end-organ performance while more definitive therapy is considered. (Level of Evidence: C)

11. Invasive hemodynamic monitoring should be performed to guide therapy in patients who are in respiratory distress or with clinical evidence of impaired perfusion in whom the adequacy or excess of intracardiac filling pressures cannot be determined from clinical assessment. (Level of Evidence: C)

12. Medications should be reconciled in every patient and adjusted as appropriate on admission to and discharge from the hospital. (Level of Evidence: C)

13. In patients with reduced ejection fraction experiencing a symptomatic exacerbation of HF requiring hospitalization during chronic maintenance treatment with oral therapies known to improve outcomes, particularly ACEIs or ARBs and beta-blocker therapy, it is recommended that these therapies be continued in most patients in the absence of hemodynamic instability or contraindications. (Level of Evidence: C)

14. In patients hospitalized with HF with reduced ejection fraction not treated with oral therapies known to improve outcomes, particularly ACEIs or ARBs and beta-blocker therapy, initiation of these therapies is recommended in stable patients prior to hospital discharge (569,570). (Level of Evidence: B)

15. Initiation of beta-blocker therapy is recommended after optimization of volume status and successful discontinuation of intravenous diuretics, vasodilators, and inotropic agents. Beta-blocker therapy should be initiated at a low dose and only in stable patients. Particular caution should be used when initiating beta blockers in patients who have required inotropes during their hospital (569,570). (Level of Evidence: B)

16. In all patients hospitalized with HF, both with preserved (see Section 4.3.2, Patients With Heart Failure and Normal Left Ventricular Ejection Fraction) and low EF, transition should be made from intravenous to oral diuretic therapy with careful attention to oral diuretic dosing and monitoring of electrolytes. With all medication changes, the patient should be monitored for supine and upright hypotension, and worsening renal function and HF signs/symptoms. (Level of Evidence: C)

17. Comprehensive written discharge instructions for all patients with a hospitalization for HF and their caregivers is strongly recommended, with special emphasis on the following 6 aspects of care: diet; discharge medications, with a special focus on adherence, persistence, and uptitration to recommended doses of ACEI/ARB and beta-blocker medication; activity level; follow-up appointments; daily weight monitoring; and what to do if HF symptoms worsen. (Level of Evidence: C)

18. Postdischarge systems of care, if available, should be used to facilitate the transition to effective outpatient care for patients hospitalized with HF (215,571--577). (Level of Evidence: B)

ADHF -- Dx & Therapy -- Class II Class IIa1. When patients present with acute HF and known or suspected acute myocardial ischemia due to occlusive coronary disease, especially when there are signs and symptoms of inadequate systemic perfusion, urgent cardiac catheterization and revascularization is reasonable where it is likely to prolong meaningful survival. (Level of Evidence: C)

2. In patients with evidence of severely symptomatic fluid overload in the absence of systemic hypotension, vasodilators such as intravenous nitroglycerin, nitroprusside or nesiritide can be beneficial when added to diuretics and/or in those who do not respond to diuretics alone. (Level of Evidence: C)

3. Invasive hemodynamic monitoring can be useful for carefully selected patients with acute HF who have persistent symptoms despite empiric adjustment of standard therapies, and

a whose fluid status, perfusion, or systemic or pulmonary vascular resistances are uncertain;
b whose systolic pressure remains low, or is associated with symptoms, despite initial therapy;
c whose renal function is worsening with therapy;
d who require parenteral vasoactive agents; or
e who may need consideration for advanced device therapy or transplantation. (Level of Evidence: C)

4. Ultrafiltration is reasonable for patients with refractory congestion not responding to medical therapy (578). (Level of Evidence: B) Class IIb1. Intravenous inotropic drugs such as dopamine, dobutamine or milrinone might be reasonable for those patients presenting with documented severe systolic dysfunction, low blood pressure and evidence of low cardiac output, with or without congestion, to maintain systemic perfusion and preserve end-organ performance. (Level of Evidence: C)

ADHF -- Dx & Therapy -- Class III

Class III

1. Use of parenteral inotropes in normotensive patients with acute decompensated HF without evidence of decreased organ perfusion is not recommended (579). (Level of Evidence: B)

2. Routine use of invasive hemodynamic monitoring in normotensive patients with acute decompensated HF and congestion with symptomatic response to diuretics and vasodilators is not recommended (580). (Level of Evidence: B)

Cardiomyopathy -- Amyloidosis

Amyloid is a proteinaceous material than stains with Congo red and demonstrates apple-green birefringence with polarized light

Clinical

•CHF associated with nondilated LV with thick walls and normal to mildly reduced LVEF

•Biventricular CHF often present although RH failure signs may predominate. Peripheral edema and ascites are common

•Negative cardiac biopsy usually rules out the condition

•If biopsy positive, must determine type of amyloid

Types of amyloidAL

•AL derived from a monoclonal Ig light chains produced by plasma cell dyscrasia

•Serum and urine immunofixation more sensitive than standard protein electrophoresis. Using both urine and serum, 97% pts have abnormal monoclonal Ig or free light chains

•Bone marrow biopsy needed to look for associated multiple myeloma

•Rapidly progressive course, 80% death within 2 years

•Rx CHF

•diuretics and salt management

•Beta-blockers used with caution b/c of negative inotropy

•ACE-I/ARBs are rarely tolerated. May cause profound hypotension

•Dig. useful only if pts need HR control with a. fib.

•Midodrine for hypotension due to autonomic neuropathy

•Rx associated plasma cell dyscrasia

•Chemo: Melphalan and prednisone, poss. role for thalidomide

Hereditary amyloidosis

•Much more indolent course than AL

Senile systemic amyloid

•Symptomatic Rx with diuretics, anticoagulation

Secondary amyloidosis

•Prognosis substantially better than in AL

Cardiomyopathy -- Hypertrophic A. DISTINCTION FROM ATHLETIC HEART

Athletic heart

LVEDD > 55, wall thickness ULN
Responds to de-training
Supernormal exercise capacity
No fibrosis on MRI, no perfusion defects

HCM

LVEDD < 45
Marked LAE
Bizarre EKG
Abnormal diastology
Reduced TDI velocity

__________________________________________________________________B. Echo features

LVH, any pattern

Obstruction not necessary

HTN, AS, subvalvular disease, infiltrative disorders need to be excluded

DDx of thick walls on echo: HTN, HCM, Renal failure, Cardiac amyloid, Glycogen storage disease, Anderson-Fabry disease, Friedreich's ataxis, Athleic adaptation

__________________________________________________________________

C. Epidemiology

Prevalence 1: 500
SCD 1%/yr
Family needs screening
Exercise: healthy lifestyle
Medication for sx only

__________________________________________________________________D. Genes responsible

B-myosin heavy chain -- MYH7

Myosin binding protein C -- MYBPC3
Cardiac troponin T -- TNNT2

___________________________________________________________________E. Genetic testing

Negative genetic testing does NOT exclude HCM

Mutation present -- genetic testing preferred for 1st degree relatives
No mutation -- imaging preferred
Adolescents q 12 - 18 mos
Adults q 5 years

___________________________________________________________________F. Treatment1. AVOID:

Avoid strenuous activity

Avoid dehydration
Avoid + inotropes, pure vasodilators (ACE-I, NTG, dihidropyridine Ca2+ ch. blockers), high dose diuretics

2. Meds to decrease obstruction:

Beta-adrenergic blockers, Verapamil, Diltiazem, Disopyramide

3. Surgical Myectomy, Alcohol septal ablation

Myectomy is first line Rx
Alcohol septal ablation is offered for patients with co-morbid conditions

4. SCD risks:

Prior VT/VF
Fam. hx SCD
Recent unexplained syncope
BP drop with exercise
NSVT
Massive septal hypertrophy (> 30 mm)

0 risks -- reassurance
1 risk -- individualize
ICD for > 2 risks,

Cardiomyopathy -- Other A. Alcohol Requires daily intake of for + 10 years:

10 oz whiskey,

32 oz wine

64 oz beer,daily

B. Amyloid Suspect if other organs involved:

Peripheral neuropathy

Swallowing disorders
Nephrotic syndrome
Macroglossia
Autonomic neuropathy

C. Causes of Myocarditis

Toxins
- Anthracyclines, Cocaine, IL-2
Infectious
Viruses: Coxsackie, Adeno, Entero
Protozoal: Trypanosoma cruzi
Bacterial
Fungal
Hypersensitivity
Various drugs
Other

__________________________________________________________________ D. Hemochromatosis

Looks like dilated CM

Suspect if DM, impotence, hyperpigmentation
Phlebotomy and Chelation can reverse cardiac abnormality

___________________________________________________________________ E. Peripartal

Heart failure of uncertain etiology occurring 1 month prior to and up to 5 months after delivery

___________________________________________________________________ F. Sarcoid

Multisystem illness

Cardiac involvement 2% clinically
African-American, female
Also Scadinavian, Irish, Japanese
Heart block, ventricular arrhythmias

Myocarditis - not Giant Cell MyocarditisPathogenesis3 pathways

Direct myocardial invasion by cardiotropic virus

2nd phase of immunological activation
Finally CD4+ lymphocytes activated, prompting clonal expansion of B cells, resulting in further myocardial injury, additional local inflammatory responses and circulating antiheart antibodies

Diagnosis

Biopsy is the gold standard
Myocarditis found in 10% pts with idiopathic DCM
CTn (T or I)
Contrast enhanced MRI

Predictors if Clinical OutcomeAdverse

Giant cell
Persistent viral genome on repeat biopsy
Elevated circulating soluble FAs and Fas ligand levels
LV enlargement and sphericity
LVEF < 45%
Pulm. HTN
BBB

Good

Fulminant clinical presentation
Short duration of sx
Myocardial infarction mimicry
borderline myocarditis histopathology
Resolution of myocarditis on repeat biopsy
Cardiac uptake on antimyosin scanning

Myocarditis -- Giant Cell Giant Cell MyocarditisPathology

Diffuse inflammation, showing macrophages and giant cells
Heart usually dilated, heavy and flabby
DDx includes granulomatous myocarditis (sarcoidosis) and lymphocytic myocarditis

Clinical

Predominant presentation is of severe CHF, which is progressive (fulminant)
Median time from onset of sx to presentation is 3 weeks
Malignant ventricular arrhythmias and SCD are prominent features
Ischemic CP, elevated CTn, systemic embolism
Cardiac MRI distinguishes GCM from ASHD but does not identify GCM specifically

Prognosis

Poor

Supportive
Immunosuppressive
MCS

Transplantation -- can recur in transplanted heart, and may respond to augmented or altered immunosuppression

Ventricular arrhythmias -- general VENTRICULAR ARRHYTHMIASOPTIC trialTested

beta-adrenergic blockers

beta-adrenergic blockers + Amiodarone
Sotalol alone

for reducing ICD shocks. Beta-adrenergic blockers + Amiodarone was the best. Sotalol not significantly better than beta-adrenergic blockers aloneStrategies for ICD programmingTiered Rx

Several VT zones, using ATP or shock

Highest zone is for VF, treated with shock

ATP

May result in termination, no effect or acceleration

Effect unpredictable -- may terminate on one occasion and accelerate on another for same rhythm

Natural hx ICD programming

ICD programming dictated by local custom and trial and error

Inappropriate Rx

Ablation is an option for persistent VT/VF

Difficult, offered only at a few centers

Ventricular arrhythmias -- Polymorphic VT 1. EKGBIzarre and variable morphology, rates 150 - 300/min2. MechanismEarly after-depolarizations, both bradycardia-dependent and bradycardia-independent

3. Causes

a) Long QT

            - congenital
            - acquired, esp. drug-induced

b) Bradycardia

c) Ischemia

d) CHF, LVH, metabolic, critical illness

4. Therapy

a) Treat underlying etiology

b) Bradycardia-dependent

         - Raise HR: pacing, isoproterenol
         - Identify drugs that prolong QT
         - Magnesium
         - K+
         - Relieve ischemia

c) Bradycardia-independent

         - Relieve ischemia
         - Class III antiarrhythmic drugs
   - Beta-adrenergic blockers

Transplantation -- Selection of Candidates.pdf
Selection of cardiac transplantation candidates in.pdfTransplantation -- Listing Status
Status 1A

Patients who must stay in the hospital and require IV drugs, a heart assist device, a ventilator, or who have a life expectancy of a week or less without a transplant. If you are under 18 years of age, you may be Status 1A with slightly less severe problems. Status 1A patients have the highest priority on the waiting list

Status 1Bc

Patients who are not confined to the hospital, but who require a heart assist device or continuous IV meds while at home (or wherever). Some of the newer assist devices do allow a patient to wait at home. Status 1B patients have the second-highest priority on the waiting list

Status 2

All other "active" patients on the transplant waiting list. If you are a Status 2 patient waiting at home, you will be seen at regular intervals by your transplant cardiologist, probably once every 4 weeks. You will have a right heart cath about every 3 months to check your pulmonary pressures. While you wait, remember to be prepared!

Status 7

Patients who are temporarily inactive, meaning they are not waiting to get that call right now for some reason

Transplantation -- Indications

Heart failure requiring mechanical assistance (e.g., respirator, IABP, or VAD) with, at worst, reversible end-organ damage

Refractory heart failure requiring continuous inotropic support and invasive monitoring

NYHA class III or IV symptoms with marked functional limitation and poor 12-month prognosis despite optimal medical therapy (peak oxygen consumption <12--14 mL/kg/min or marked serial decline, progression of symptoms, or clinical instability)

Recurrent or rapidly progressive medically unresponsive heart failure symptoms

Severe hypertrophic or restrictive cardiomyopathy with NYHA class IV symptoms

Severe, refractory angina pectoris despite optimal β-blocker, calcium channel blocker, and nitrate therapy, not amenable to revascularization, accompanied by evidence of myocardial ischemia within the first two stages of a standard Bruce exercise protocol

Recurrent symptomatic, life-threatening ventricular arrhythmias despite all appropriate conventional medical and surgical modalities

Cardiac tumors confined to the heart with a low likelihood of metastasis at time of transplant

Hypoplastic left heart syndrome

Complex congenital heart disease with progressive ventricular failure, not amenable to conventional surgical repair or palliation

Transplantation -- Contraindications 1. Irreversible Pulm. HTN         a) PVR > 5 WU         b) PVRI > 6         c) TPG > 16 - 20
         d) SPAP > 50 - 60 or > 50% of systemic pressure

2. Age > 70

3. Active systemic infection

4. Active malignancy or recent malignancy with high risk of recurrence

5. Diabetes mellitus with:

        a. End-organ damage : proliferative retinopathy, nephropathy
        b. Poor glycemic control

6. Obesity

        a. BMI > 30
        b. Weight > 140% IBW

7. Severe PVD

8. Systemic process with high rate of recurrence in transplant heart

        a.Amyloidosis
        b.Sarcoidosis
        c.Hemochromatosis

9. Irreversible severe renal, hepatic or pulmonary disease

10. Psychosocial factors

◆Poor home Support, substance abuse, psychiatric illness, hx poor medical compliance

Transplantation -- General Care of the patient

General Care of Heart Transplantation Patients

1. Donor Hearts and age:

•        <45 OK
•        between 45 and 55 OK when ischemic times < 4h
•        > 55 -- don’t use

2. Hearts from donors with infection OK if:

•        infection community-acquired
•        no LV dysfunction
•        no myocarditis or endocarditis
•        donor receives antibiotics
•        blood cultures before procurement are negative

3. Hearts from non IV Cocaine users OK

4. Don’t use Hearts from EtOH abusers

5. OK to use hearts with normally functioning bicuspid AV valves

6. Don’t use hearts if

•intractable ventricular arrhythmias

•LVEF < 40%

•Dopamine > 20 ug/kg/min

•Discrete WMA on echo

7. Don’t use hearts from patients weighing more than 30% below that of the recipient8. A male donor of average weight (70 kg) can be safely used for any size recipient irrespective of weight

9. Use of a female donor whose weight is more than 20% lower than that of a male recipient should be viewed with caution

10.Ischemic times should be less than 4h

11.TR judged to be more than moderate b/4 Tx should be re-evaluated within 24 h of tx by echo

12.Isoproterenol and theophylline can be used post Tx to increase HR

13.Bradycardia will not respond to atropine

14. Maintain CVP between 5 and 12

15.Initial therapy of AMR can include:

•        Immunoadsorption and corticosteroid (CS)
•        plasmapheresis/low dose of IV Ig and CS
•        Rituximab can be added to reduce the risk of recurrent rejection
•        switch to tacrolimus (TAC) in patients receiving cyclosporine
•        based immunosuppression
•        increased doses of mycophenolate mofetil (MMF), and CS

16. Not recommended for routine rejection monitoring in place of EMB:

•        echocardiography
•        EKG
•        MRI
•        BNP, CTnT, CRP
•        Systemic inflammatory markers

16.Use statins 1 - 2 weeks after Tx regardless of lipid levels. Use lower doses than usual b/o combined calcineurin use (CYP mateabolism)

17.For symptomatic acute cellular rejection:

•Hospitalize

•Perform EMB

•Give high dose CS IV

•ATG/Thymoglobulin can be given as adjunct

•Adjust maintenance Rx

•Give antimicrobial prophylaxis for opportunistic infections DO NOT GIVE IL-2 inhibitors

18. For Asymptomatic cellular rejection:

•If severe by EMB, treat regardless of sx : Give high-dose IV CS

•If moderate, give either oral or IV CS

•Adjust maintenance Rx

•Give antimicrobial prophylaxis for opportunistic infections

19. For hyperacute rejection:

•Give high-dose IV CS

•plasmapheresis

•IV Ig

•Cytolytic immunosuppressive Rx

•IV CNI (CYA, TAC) and MMF IV

•inotropes

•MCS

20.Withdraw steroids after 3 - 6 mos in low-risk pts21. Use lower levels of CNI when used with MMF22.Consider PSI in place of CNI 6 mos after Tx

23.Don't substitute a PSI for MMF just to lower CNI nephrotoxicity

24.Don't substitute PSI for MMF sooner than 3 mos after Tx

25.Reduce CNI dose in HT pts who have seizures or encephalopathy. If seizures persist, substitute PSI for CNI

26.For CAV:

•        Give statins
•        Treat conventional risk factors
•        Perform annual or biannual coronary angiography
•        IVUS optional
•        When established CAV present, may substitute PSI for MMF
•        Noninvasive imaging is an adjunct but not a replacement for coronary
angiography
•        If PCI done, use drug-eluting stents
•        CABGS is an option
•        Retransplantation is an option if CAV severe and no contraindication exists

27.Malignancy after Tx:

•        Screen for breast, colon and prostate cancers as in general population
•        Yearly derm. exams, education on prevention
•        Plan for (PTLD) in HT recipients should be in place
•        No need to reduce immunosuppressive Rx if solid tumors develop in Tx
pts
•        Chronic immunosuppression should be minimized in HT recipients as much as possible, particularly in patients at high risk for malignancy

28.CKD after Tx

•        Minimize CNI exposure: substitute MMF for AZA
•        Use ACE-I or ARB
•        Strict glucose and BP control
•        ESA for Hgb below 11?
•        Use CCB when ACE-I alone ineffective

29.DM after Tx

•        Consider CS sparing regimens
•        Decrease CNI doses

30.Oral hypoglycemic agents should be discontinued preoperatively

31.Infection prophylaxis

•        Pre-operative antibiotic prophylaxis should be used before the transplant operation
•        Drugs should be selected based upon their activity against usual skin flora, specifically Staphylococcus species.
•        If a chronically infected device such as a VAD or a pacemaker is present, then peri-operative antibiotics should be selected based on microbiologic sensitivities
•        In the event that the donor had an ongoing bacterial infection, a course of suitable antibiotics should be considered

32. CMV prophylaxis

•Prophylaxis against CMV should be initiated within 24 to 48 hours after HT.

•The CMV serologic status of the donor and recipient may be used to stratify the patient as low-risk, intermediate-risk, or high-risk for developing a CMV infection

•Intravenous ganciclovir may be administered to intermediate and high-risk patients, whereas patients at low-risk for CMV infection may only receive anti-herpes simplex virus prophylaxis with acyclovir

33. Antifungal prophylaxis

•Anti-fungal prophylaxis to prevent mucocutaneous candidiasis should be initiated once the recipient is extubated

•The agents most commonly used are nystatin (4–6 mL [400,000 to 600,000 units] 4 times daily, swish and swallow) or clotrimazole lozenges (10 mg)

34. Pneumocystis jiroveci

•Prophylaxis against Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia and Toxoplasma gondii (in indicated cases) should also be initiated in the early post-operative period

•Trimethoprim/sulfamethoxazole (80 mg TMP/160 mg SMZ, 1 single- or doublestrength tablet per day) is the most commonly used medication

•In the setting of a sulfa allergy or glucose- 6-phosphate dehydrogenase deficiency, alternative regimens can be used, including:

•Aerosolized pentamidine (AP) isethionate (300 mg every 3–4 weeks). Dapsone (diaminodiphenylsulfone) with or without TMP or pyrimethamine (50–100 mg/day)

•Pyrimethamine may be administered weekly (25 or 50 mg) to supplement dapsone (50–100 mg/day)

•Dapsone is metabolized via the hepatic cytochrome P-450 system (CYP3A). Atovaquone (1500 mg PO QD)

•Clindamycin and pyrimethamine

35. Screening for PRA

•Screening panel reactive antibodies (PRA) should be performed in all HT candidates

•When the PRA is elevated (10%) further evaluation is recommended

Transplantation -- Hyperlipidemia Hyperlipidemia

An HMG-CoA reductase inhibitor is used in the majority of transplant recipients, regardless of lipid profile
Not only do the HMG-CoA reductase inhibitors effectively treat the frequently encountered post-transplant hypercholesterolemia, they appear to decrease hemodynamically significant rejection
The combination of a calcineurin inhibitor and an HMG-CoA reductase inhibitor increases the risk of rhabdomyolysis
HMG-CoA reductase inhibitors are started at low dosage and the dosage is increased periodically while levels of creatine kinase and liver enzymes are monitored
All patients are encouraged to limit intake of cholesterol and other fats, maintain ideal body weight, and exercise
The goal for low-density lipoprotein cholesterol is less than 70 to 100 mg/dL
Whereas HMG-CoA reductase inhibitors are first-line therapy, the use of gemfibrozil or fenofibrate can be successful in some patients, particularly in the setting of hypertriglyceridemia
Combining an HMG-CoA reductase inhibitor with gemfibrozil or nicotinic acid in lipid-lowering doses (≥1 g/d) can cause rhabdomyolysis, and these combinations are used cautiously in transplant patients
Bile acid sequestrants and fish oil (omega-3 free fatty acids) are infrequently used to treat hyperlipidemia after transplantation

Transplantation -- Hypertension

Hypertension

1.After transplantation, hypertension occurs in approximately two thirds of recipients

2.less frequently and less severely with tacrolimus than with cyclosporine

3.Moderate limitation of salt intake, maintenance of ideal body weight, and moderate exercise are encouraged in hypertensive cardiac transplant recipients

4.most still require pharmacologic treatment

5.Generally, blood pressures consistently greater than 140/90 mm Hg are treated

6.angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), calcium channel blockers, and β-blockers in conventional dosages are effective, alone or in combination

7.Care is taken when using ACE inhibitors or ARBs as some patients are prone to hyperkalemia due to renal effects of the calcineurin inhibitors

8.The use of either diltiazem or verapamil necessitates lowering of the dosages of cyclosporine or tacrolimus and monitoring cyclosporine or tacrolimus levels

9.Diuretics are effective in some patients, although rarely as monotherapy

10.Dehydration should be avoided with the concomitant use of cyclosporine or tacrolimus

Transplantation -- Infection time course DA6C90FF3FIGURE 90.3. The risk of infection from various etiologic agents peaks at different times after cardiac transplantation. (Source: Adapted from
Miller LW, Naftel DC, Bourge RC, et al. Infection after heart transplantation: a multiinstitutional study. J Heart Lung Transplant 1994;13:384
, with permission.)

Transplantation -- Infections
Infectious Complications

The types of infections expected in cardiac transplant recipients vary depending on the time from transplantation, as the intensity of immunosuppression administered varies directly with the propensity for rejection

Bacteria and viruses account for more than 80% of infections after transplantation

A. Most common bacterial infections early after transplantation are nosocomial (nfected intravascular catheters or lines and pneumonias)

The risk decreases rapidly over time

B. The most common viral infections are caused by cytomegalovirus (CMV) and herpes simplex

Although CMV infection used to be associated with significant morbidity and mortality, the use of ganciclovir has significantly improved the prognosis

Patients who are CMV seronegative who receive a heart from a seropositive donor are at greatest risk for aggressive disease

C. Although fungi and protozoa account for less than 15% of infections after transplantation, such infections can be associated with the worst prognosis

Fungal infections occur
- in patients who require intensive treatment over a prolonged period before transplantation, who develop significant rejection in the setting of a bacterial infection that requires the use of broad-spectrum antibiotics

D. Given the potential morbidity and mortality associated with infections during the first posttransplant year, infection prophylaxis is common

Prophylactic regimens are commonly used against

CMV (if either recipient or donor is seropositive)
toxoplasmosis (especially if the recipient tests negative and the donor tests positive)
Pneumocystis carinii
Candida albicans
herpes simplex

Transplantation -- Infection Prophylaxis

TABLE 90.6 Infection Prophylaxis After Cardiac Transplantation

Organism	Regimen
CMV (recipient seropositive)	Ganciclovir 5 mg/kg IV BID while IV in place, followed by valganciclovir, 900 mg PO daily until 3 months posttransplant
CMV (recipient seronegative and donor seropositive)	Ganciclovir 5 mg/kg IV BID while IV in place, followed by valganciclovir, 900 mg PO daily until 6 months posttransplant
Herpes simplex	Acyclovir 200 mg PO QID until corticosteroid dosage <20 mg prednisone/d
Epstein-Barr virus (recipient seronegative and donor seropositive)	Acyclovir 800 mg PO QID for 12 mo, then 200 mg PO QID
Toxoplasma gondii (donor or recipient seropositive)	Pyrimethamine 25 mg PO daily for 6 weeks and leucovorin calcium 5–10 mg PO daily for 6 weeks
Pneumocystis jiroveci	Trimethoprim maleate/sulfamethoxazole 160 mg/800 mg PO 3–7 times per week or dapsone 75–100 mg PO daily if sulfa allergic
Candida albicans	Nystatin 10 mL swish and swallow QID or clotrimazole troche PO QID until corticosteroid dosage (prednisone) <20 mg/d
Abbreviations: BID, twice daily; IV, intravenous line; PO, by mouth; QID, four times daily.

Transplantation -- Malignancy

Malignancy

After transplantation recipients have an increased risk of malignancy compared with the general population

The overall degree of immunosuppression may be more important than any intrinsic property associated with a particular drug

Care is taken to avoid overimmunosuppression

By 5 years after transplantation, nearly 10% of survivors have experienced a malignancy

Fortunately, nearly half are skin cancers, occurring predominantly in those who would otherwise be at risk

Because locally invasive skin cancer can be fatal if not treated promptly and adequately, routine screening is performed

Posttransplant lymphoproliferative disease (PTLD) occurs in less than 2% of patients

PTLD can be refractory to any treatment or relatively localized and benign, responding simply to reduction in immunosuppression

The Epstein-Barr virus, a lymphotropic virus that infects more than 90% of the population by adulthood, is thought to be the etiologic agent responsible for most cases of PTLD

Although other malignancies occur in heart transplant recipients, the behavior of prostate, breast, and cervical cancer and of other solid tumors seems no different than in the general population.

Transplantation -- Osteopenia

•Osteoporosis

•By the time most patients undergo cardiac transplantation, the risk of osteoporosis and other skeletal complications is high

•Prolonged inactivity and, in some cases, prolonged heparin administration can demineralize bone and put the patient at risk for complications

•Further bone loss occurs owing to high-dose corticosteroid therapy

•Bone loss is rapid in the first 6 months after transplantation and is most marked in the lumbar spine

•Vertebral compression fractures and aseptic necrosis of the femoral head are among the most common skeletal problems after heart transplantation

•Because of the morbidity associated with osteoporosis, patients at risk are treated

•All patients with evidence of pretransplant osteoporosis receive supplemental calcium and vitamin D while awaiting transplantation and indefinitely thereafter

•Alendronate or other bisphosphonates may effectively increase bone density and can be safely added to calcium and vitamin D supplementation

•Postmenopausal women are generally prescribed estrogen replacement therapy

Transplantation -- Renal failure

Renal Insufficiency

•Five years after heart transplantation, 8.5% of recipients have a serum creatinine level higher than 2.5 mg/dL, and 1.9% require long-term dialysis (1)

•Although some renal dysfunction is related to preexisting renal disease, most is acquired

•Cyclosporine and tacrolimus are nephrotoxic and probably account for the majority of renal problems

•Minimizing the dosages of these drugs or implementing calcineurin inhibitor-free strategies, avoiding dehydration, and searching carefully for non-immunosuppression–related reversible causes are warranted (2,3,4).

Transplantation -- Surgery and Pregnancy

Management of the Cardiac Transplant Recipient Undergoing Surgery

•Surgery

•Because of bone complications, biliary disease, and other surgically amenable problems, many cardiac transplant recipients undergo noncardiac surgery

•antibiotic prophylaxis is used for dental procedures and other procedures in which the risk of septicemia is high

•risk associated with noncardiac surgery depends on the status of the allograft

•In patients without ongoing rejection, significant coronary disease, or left ventricular dysfunction, the risk is low

•Before elective major surgical procedures, an endomyocardial biopsy is typically performed, and the most recent angiogram is reviewed

•Patients receiving corticosteroids within the preceding 9 months receive stress doses of corticosteroids

•If intravenous immunosuppressants are required because of prolonged ileus, appropriate dosage adjustments must be made

•Pregnancy

•Successful pregnancies after heart transplantation have been reported

•Maternal and fetal risk is undoubtedly higher than in the general population

•Once the recipient is pregnant, close collaboration with an obstetrician knowledgeable about high-risk cases is warranted to avoid teratogenic drugs and manage the pregnancy

•Immunosuppressive drug levels are monitored frequently, as volume changes and metabolic changes occur during pregnancy

•Radiation exposure can be minimized by using echocardiographically guided endomyocardial biopsies.

Rejection -- types Types of Cardiac Allograft Rejection Rejection defined

histologically
functionally
clinically

Categories

hyperacute
acute cellular
antibody-mediated rejection
the term “chronic rejection” generally refers to CAV

Rejection -- Microscopy See attached image

Top panel -- Normal

Middle -- mild perivascular rejection in 3 spots

Lower panel -- severe rejection

rejection0-1Rejection -- Acute Cellular Acute cellular rejection

most common form of rejection
occurs in one third to one half of heart transplant recipients

the propensity toward allograft rejection decreases over time and nearly half of the rejection episodes occur in the first 2 to 3 months
late rejection can occur
Rejection occurring early after transplantation tends to be more aggressive and life threatening than late-occurring rejection
Acute cellular rejection is most frequently diagnosed by endomyocardial biopsy graded in accordance with the International Society for Heart and Lung Transplantation (ISHLT) criteria

TABLE 90.4 Acute Cellular Rejection Grading (ISHLT)
Grade	Rejection severity	Description
0 R	None	No interstitial cellular infiltrates
1 R	Mild	Interstitial and/or perivascular cellular infiltrate with ≤1 focus of myocyte damage
2 R	Moderate	≥2 foci of cellular infiltrate with associated myocyte damage
3 R	Severe	Diffuse cellular infiltrate with multifocal myocyte damage, with or without edema, hemorrhage, or vasculitis
Abbreviations: ISHLT, International Society for Heart and Lung Transplantation; R, refers simply to a revision of an earlier scale.

Rejection -- Antibody-mediated

Antibody-mediated rejection

otherwise unexplained cardiac allograft dysfunction

histologic evidence

some combination of the two

manifests as a scant cellular infiltrate with abundant co-localized immunoglobulin and complement components in the allograft microvasculature
characteristic findings are typically seen on one or more biopsy specimens

Rejection -- Hyperacute

Hyperacute rejection

a vigorous immune response that takes place within minutes to hours, due to preformed, donor-specific antibodies in the recipient
outcome is uniformly fatal
Best way to prevent is to avoid transplanting a donor heart into a patient who is sensitized to the donor (a positive donor-specific cross-match)

Candidates screened for possible donor-specific antibodies using a panel reactive antibody (PRA) test
PRA testing is performed by exposing recipient serum to lymphocytes from 50 or more random individuals
Normal result of 0% reactivity suggests a low risk that a retrospective cross-match would be positive
The sensitivity of the PRA can be increased using alternate technologies that enable determination of HLA antibody specificities
For elevated PRA reactivity, prospective cross-matching is generally warranted

Rejection -- Dx and Surveillance

Diagnosis

Surveillance is by routine endomyocardial biopsies
EMB is initially performed weekly and then at gradually increasing intervals
Twelve to 24 months after transplant, biopsies are performed every 3 to 6 months
Over time, some patients are managed without routine endomyocardial biopsies
After the diagnosis of rejection, the endomyocardial biopsy interval is, of course, altered

Clinically, most rejection episodes manifest with no signs or symptoms and are detected only by surveillance endomyocardial biopsies

If the episode is symptomatic, the most frequent symptom is fatigue

Later, exercise intolerance or frank heart failure symptoms may occur

Physical findings, if present, may include
- relative hypotension (decrease in systolic blood pressure of >20 mm Hg from baseline)
- elevated jugular venous pressure
- a third heart sound

Symptoms or signs, such as those mentioned, prompt an urgent endomyocardial biopsy
An enlarging pericardial effusion or worsened indices of systolic or diastolic function determined by echocardiography may herald rejection
Fever is an infrequent manifestation of rejection
Atrial or ventricular arrhythmias are considered indicative of allograft rejection until proven otherwise.

Rejection -- Prevention and Therapy I

Multiple agents used to minimize the toxicity of individual agents and to block the immune system in multiple locations

Generally, 3 agents with differing mechanisms of action and toxicities are used

a calcineurin inhibitor (cyclosporine or tacrolimus)
an antiproliferative (azathioprine, mycophenolate mofetil, mycophenolic acid [extended release enteric coated], or an mTOR inhibitor)
a corticosteroid

To avoid the early use of cyclosporine or tacrolimus in patients at high risk of renal dysfunction (serum creatinine level >2.0–3.0 mg/dL before transplant), antilymphocyte preparations or an IL-2 receptor blocker may be used perioperatively

Over time, dosages of all agents may be decreased accordingly

Calcineurin inhibitors are usually maintained long term at levels less than half of those used early after transplant

Prednisone can safely be withdrawn in patients who demonstrate a low propensity to reject (40).

Treatment of rejection depends on several factors

severity of rejection (ISHLT grade of biopsy)
time since transplant
rejection and immunosuppressive history
hemodynamic status of the patient

Rejection -- Prevention and Therapy II

Mild rejection

Mild rejection in hemodynamically stable patients (asymptomatic) is generally not treated
even mild rejection may increase the likelihood of CAV
Mild rejection warrants augmentation of immunosuppression if allograft dysfunction present

Rejection may be treated by changing the maintenance immunosuppression

a different calcineurin inhibitor or antiproliferative agent could be used
In treating rejection, one generally optimizes or increases the dosages of maintenance immunosuppressants and markedly increases corticosteroid dosages
In corticosteroid-refractory rejection or in rejection episodes associated with hemodynamic instability, antilymphocyte antibodies are added

Moderate rejection

If patient hemodynamically stable, is usually treated initially with a several-day course of either intravenous or high-dose oral corticosteroids
If a subsequent biopsy specimen shows resolution, the maintenance dosages are resumed
If a subsequent biopsy specimen does not show resolution, however, a second course of intravenous corticosteroids is used
Failure of a second course of corticosteroids leads to the use of antilymphocyte antibodies

Immunosuppression -- Pathophysiology I

Figure from Textbook of Cardiovascular Medicine (Topol et al., eds)

Mechanism of action of immunosuppressive drugs.

Immunosuppression -- Pathophysiology II

Allotransplantation

Transplantation of an organ between members of the same species is known as allotransplantation
Alloantigens are molecules recognized as foreign (or non-self) by the recipient immune system
In the absence of immunosuppression, destruction of the alloantigens---and the organ bearing them---occurs

HLA
- HLA antigens are serologically identified alloantigens that have been shown to correspond to the human major histocompatibility complex (MHC)
- Whereas HLA antigens have distinctly different roles in the rejection process, prospective HLA matching is generally not possible in heart transplantation
- The sequence of events leading to cardiac allograft rejection encompasses antigen recognition, primary and secondary signals for T-cell activation, and T-cell proliferation and differentiation
Sequence of rejection

After the heart is transplanted, antigen-presenting cells of recipient or donor origin migrate to secondary lymphoid organs where donor antigen is presented to T cells
Donor antigen engages T-cell receptors (primary signal), and CD80 and CD86 on the antigen-presenting cell engage CD28 on the T cell (secondary signal)
The primary and secondary signals activate at least three signal transduction pathways
- (a) the calcium -- calcineurin pathway that activates the transcription factor, nuclear factor of activated T cells (NFAT)
- (b) the mitogen-activated protein kinase pathway that activates the transcription factor, activating protein 1
- (c) the protein kinase-C nuclear factor κB pathway that activates the transcription factor, NF-κB
The combined effect of these three pathways is further activation of the antigen-presenting cell, by the expression of CD154 on the T cell, which interacts with CD40 on the antigen presenting cell, expression of the interleukin (IL)-2 receptor α chain, CD25, and synthesis of IL-2. Activation of the IL-2 receptor delivers growth signals through the molecular-target-of-rapamycin (mTOR) pathway, which initiates the cell cycle
T cells are activated and undergo clonal expansion and differentiation to express effector functions. Under the influence of pro-inflammatory cytokines, effector cells for cell-mediated and antibody-mediated immunity are generated. Destruction of the allograft occurs via involvement of antibody, cytotoxic T lymphocytes, macrophages, and cytokines.

Immunosuppression -- Immunosuppressive Drugs

TABLE 90.5 Pharmacology of Immunosuppressive Agents
Agent	Identification	Mechanism of action	Administration	Toxicity	Drug interactions and uses
Cyclosporinea	Cyclic undecapeptide produced by Tolypocladium inflatum Gams	Inhibits calcineurin	PO or IV, oral to IV dose adjustment is 3:1, oral dosage 3–6 mg/kg/d, monitor levels	Nephrotoxicity, hypertension, gingival hyperplasia, hirsutism, tremor, headache, paresthesias	Metabolism decreased by ketoconazole, diltiazem hydrochloride, verapamil hydrochloride, erythromycin, cimetidine, grapefruit; metabolism increased by phenytoin, phenobarbital, isoniazid, rifampin, carbamazepine; used in long-term maintenance
Tacrolimus	Macrolide isolate of Streptomyces tsukubaensis	Inhibits calcineurin	PO or IV, oral to IV dose adjustment is 5:1, oral dose 0.05–0.15 mg/kg/d, monitor levels	Nephrotoxicity, hypertension, tremor, headache, flushing, paresthesias, glucose intolerance	Metabolism decreased by ketoconazole, diltiazem, verapamil, erythromycin, cimetidine, grapefruit; metabolism increased by phenytoin, phenobarbital, isoniazid, rifampin, carbamazepine; used in long-term maintenance
Azathioprine	Prodrug of 6-mercaptopurine	Inhibits purine biosynthesis	PO or IV, 1–2 mg/kg/d, WBC to remain >4,500/mm3	Anemia, leukopenia, pancreatitis, cholestatic jaundice, hepatitis	Metabolism decreased by allopurinol which inhibits xanthine oxidase. When used with allopurinol, azathioprine dosage is decreased by two thirds and WBC monitored; used in long-term maintenance
Mycophenolate mofetil	Morpholinoethylester of mycophenolic acid	Inhibits inosine monophosphate dehydrogenase, inhibiting purine biosynthesis	PO or IV, 2,000–6,000 mg/d.	Gastrointestinal distress, leukopenia, anemia	No significant interactions; used in long-term maintenance
Mycophenolic acid	Enteric-coated, extended-release formulation	Inhibits inosine monophosphate dehydrogenase, inhibiting purine biosynthesis.	PO only, 1,440–4,320 mg/d	Gastrointestinal distress, anemia, leukopenia	No significant interactions; used in long-term maintenance
Sirolimus	Macrocyclic triene produced by Streptomyces hygroscopicus	Inhibits mTOR, inhibiting cell cycling	PO only, 1–2 mg/d	Hypertriglyceridemia, thrombocytopenia, leukopenia, rash, gastrointestinal distress	Metabolism decreased by diltiazem and ketoconazole; metabolism increased by rifampin; interactions probably similar to those for cyclosporine; used in long-term maintenance
Everolimus	Derivative of sirolimus	Inhibits mTOR, inhibiting cell cycling.	PO only, 1.5–3.0 mg/d.	Hypertriglyceridemia, thrombocytopenia, leukopenia, rash, gastrointestinal distress	Metabolism decreased by diltiazem and ketoconazole; metabolism increased by rifampin; interactions probably similar to those for cyclosporine; used in long-term maintenance
Corticosteroids	Synthetic or semisynthetic analogs of adrenocorticotropic hormones	Multiple; inhibits release and action of various interleukins, interferes with antigen receptor interactions	PO or IV with methylprednisolone and hydrocortisone (no significant oral to IV dose adjustment), PO with prednisone, prednisone 1 mg = hydrocortisone 4 mg = methylprednisolone 0.8 mg; maintenance dosage of prednisone is 0.0–0.1 mg/kg/d	Pituitary–adrenal suppression, cushingoid habitus, glucose intolerance, hyperlipidemia, hypertension, posterior subcapsular cataracts, myopathy, osteoporosis, skin fragility, PUD	Multiple drug interactions, none clinically significant; used in long-term maintenance and in the treatment of established rejection episodes.
Muromonab-CD3 antibody (OKT3)	IgG2A murine monoclonal immunoglobulin molecule	Binds to the CD3 surface antigen of lymphocytes, inhibits antigen recognition, opsonizes lymphocytes	IV only, 2.5–5.0 mg/d	Fever, chills, gastrointestinal distress, pulmonary edema, HAMA formation	No interactions; used in early rejection prophylaxis and in the treatment of rejection
Antithymocyte globulin (ATG)	Equine polyclonal antibodies to human thymocytes	Opsonizes lymphocytes.	IV only, 10–20 mg/kg/d	Fever, chills, serum sickness, leukopenia, thrombocytopenia	No interactions; used in early rejection prophylaxis and in the treatment of rejection
Thymoglobulin	Rabbit polyclonal antibodies to human thymocytes	Opsonizes lymphocytes	IV only, 0.75–1.50 mg/kg/d	Fever, chills, serum sickness, leukopenia, thrombocytopenia	No interactions; used in early rejection prophylaxis and in the treatment of rejection
Daclizumab	Chimeric monoclonal IgG1 antibody	Blocks the IL-2 receptor α chain (CD25)	1 mg/kg IV once at transplant, repeated, 4 times at 2-wk intervals	Gastrointestinal distress	No interactions; used in early rejection prophylaxis
Basiliximab	Chimeric monoclonal IgG1K antibody	Blocks the IL-2 receptor α chain (CD25)	20 mg IV at transplant and repeated 4 d after	Gastrointestinal distress	No interactions; used in early rejection prophylaxis
aCyclosporine is available in two formulations, oil based and microemulsion based. The latter is associated with better bioavailability. Abbreviations: PO, by mouth; IV, by vein; WBC, white blood cell count; PUD, peptic ulcer disease; HAMA, human antimouse antibody; IgG, immunoglobulin G; IL, interleukin; mTOR, molecular target of rapamycin.

Immunosuppression -- Induction therapy

IMMUNOSUPPRESSION

•Major sequelae of immune suppression are infection and malignancy

•Immunosuppressive regimens can be classified as:
- •induction
- •maintenance
- •anti-rejection

3 GENERAL PRINCIPLES

•immune reactivity and tendency toward graft rejection are highest early (within the first 3-6 months) after graft implantation and decrease with time

•use low doses of several drugs with non-overlapping toxicities in preference over higher (and more toxic) doses of fewer drugs whenever feasible
•Avoid too intense immunosuppression, because it leads to a myriad of undesirable effects including susceptibility to infection and malignancy

Induction Therapy

•Allows delayed initiation of nephrotoxic immunosuppressive drugs in patients with compromised renal function
•Provides some flexibility with respect to early steroid withdrawal
•Delay of early rejection
•Possible increase in late rejection
•Possible increased rates of infection and malignancy
•Patients at highest risk for fatal rejection may benefit:
- •younger patients
- •African American patients
- •high number of HLA mismatches
- •patients on ventricular assist devices with high levels of pre-formed antibodies

Immunosuppression -- Agents used in Induction therapy

A. Interleukin-2 receptor antagonists

•2 available agents, Basiliximab (Simulect) and Daclizumab (Zenapax)
•Anti-IL-2 receptor monoclonal antibodies

•Selectively bind to the IL-2 receptor of T-lymphocytes, blocking binding of IL-2 to the receptor complex
•Exert immunosuppressive effects by inhibiting IL-2 mediated T-lymphocyte proliferation
•Compared to OKT3 and anti-thymocyte antibodies, this class of drugs has a significantly lower incidence of drug-related adverse reactions

B. Anti-thymocyte antibodies

•Cause rapid depletion of T-lymphocytes by inducing complement-mediated cytolysis and cell-mediated opsonization in the spleen and liver
•2 agents are ATGAM, Thymoglobulin
•Thymoglobulin® may result in a lower incidence of both short and long-term acute rejection compared to ATGAM®, possibly because of more profound and durable lymphopenia after Thymoglobulin® administration
•Major acute side effects associated with this class of drugs include a serum sickness reaction characterized by fevers, chills, tachycardia, hypertension or hypotension, myalgias, and rash
•Typically noticed during the first or second drug infusion and can be treated by temporarily stopping the drug infusion and restarting at a lower infusion rate
•Pre-medication with intravenous glucocorticoids, antihistamines, antipyretics, and H2 blockers can prevent or reduce the severity of symptoms
•Dose-dependent leukopenia (30-50 percent) and thrombocytopenia (30-40 percent) have also been observed and typically respond to dose reduction or drug discontinuation for severe cases (WBC < 2,000 cells/mm3 or platelet count < 50,000 cells/mm3)
•Do not induce a host antibody response to horse or rabbit sera and can be re-used for the treatment of allograft rejection
•Long-term side effects include a pre-disposition to opportunistic infections, particularly with cytomegalovirus and a possible increase in the incidence and aggressiveness of post-transplant malignancies

C. Muromonab OKT3

•Cause rapid depletion of T-lymphocytes by inducing complement-mediated cytolysis and cell-mediated opsonization in the spleen and liver
•Several acute and long-term side effects
•The first or second drug dose is typically associated with a cytokine release syndrome characterized by fevers, rigors, nausea, vomiting, diarrhea, hypotension, chest pain, dyspnea or wheezing, arthralgias, and myalgias
•Can be attenuated by pre-medication with intravenous steroids, antihistamines, antipyretics, and H2-blockers
•Rare life-threatening complications have included pulmonary edema, aseptic meningitis, and encephalopathy
•Long-term adverse reactions include an increased risk of life-threatening opportunistic infections, particularly with cytomegalovirus and post-transplant lymphoproliferative disorders
•OKT3 can elicit a host anti-mouse antibody response that can blunt future drug efficacy and increase the risk of antibody-mediated rejection

Immunosuppression -- Calcineurin Inhibitors

Most maintenance immunosuppressive protocols employ a three-drug regimen

•a calcineurin-inhibitor (cyclosporine or tacrolimus)

•an antimetabolite agent (mycophenolate mofetil or less commonly azathioprine)

•tapering doses of glucocorticoids over the first year post-transplantation

Calcineurin InhibitorsCalcineurin is responsible for the transcription of IL-2 and several other cytokines, including TNF alpha, granulocyte-macrophage colony-stimulating factor, and interferon-gamma. Inhibition results is blunting of T-lymphocyte activation and proliferation in response to alloantigens

Tacrolimus

•Tacrolimus is the most widely used Calcineurin inhibitor

•Tacrolimus has similar effiicacy to cyclosporin and fewer side-effects

•improved renal function

•less HTN

•less hyperlipidemia

•perhaps more DM

•less biopsy proven rejection

CyclosporineOlder oil-based formulation had variable and incomplete absorptionNewer modified microemulsion formulations that result in improved and more reproducible drug absorptionDrug is typically titrated to achieve therapeutic 12-hour trough levels
Cyclosporine levels are kept highest in the first year post-transplantation (200-350 ng/mL) and lowered in subsequent periods (100-200 ng/mL)

Immunosuppression -- Antiproliferative agents

Interfere with the synthesis of nucleic acids and exert their immunosuppressive effects by inhibiting the proliferation of both T and B lymphocytes

Azathioprine

Major side effects is dose-dependent myelosuppression, particularly leukopenia

Azathioprine should be temporarily withheld if the white cell count falls below 3000/mm2 or drops by 50 percent compared to the previous value.
Other potentially serious side effects include hepatotoxicity and pancreatitis

Mycophenolate mofetil

Has replaced azathioprine as the preferred antimetabolite agent in recent years
A prodrug that is rapidly hydrolyzed to its active form, mycophenolic acid (MPA), a reversible inhibitor of inosine monophosphate dehydrogenease, a critical enzyme for the de-novo synthesis of guanine nucleotides
Lymphocytes lack a key enzyme in the guanine salvage pathway and are dependent upon the de novo pathway for the production of purines necessary for RNA and DNA synthesis
MMF therefore inhibits both T- and B-lymphocytes proliferation
Compared with azathioprine, mycophenolate mofetil was associated with a significant reduction in both mortality and in the incidence of treatable rejection
Not nephrotoxic
Causes less bone marrow suppression compared to azathioprine
Main side effects include dose related leukopenia and gastrointestinal toxicities such as nausea, gastritis, and diarrhea

Immunosuppression -- Proliferative Sgnal inhibitors

PROLIFERATION SIGNAL INHIBITORS

Also known as mammalian target of rapamycin (mTOR) inhibitors

renal insufficiency

cardiac allograft vasculopathy

malignancies in an attempt to reverse or slow progression of these conditions

high incidence of drug-related adverse effects, including delayed sternal wound healing after transplantation, may limit the widespread use of these agents as de novo therapy following transplantation

Two drugs are Sirolimus and Everolimus
Are structurally similar to Tacrolimus
Exert their immunosuppressive effects via a calcineurin-independent mechanism
Drug-immunophilin complex inhibits a protein kinase in the cytoplasm called mammalian target of rapamycin (mTOR)
Result is inhibition of both T- and B-cell proliferation in response to cytokine signals

A. Sirolimus

Biopsy proven rejection less
CAV less
Survival similar

Major toxicities

no inherent nephrotoxic effects; can potentiate the efficacy and nephrotoxic effects of the calcineurin inhibitors
when these agents are used together, the dosage of the calcineurin inhibitor should be reduced by approximately 25 percent

most common drug-related toxicities include
- hyperlipidemia
- oral ulcerations
- lower extremity edema
- bone marrow suppression with leukopenia, thrombocytopenia, and anemia
- post-surgical wound healing complications, as well as an increase in the incidence of pleural and pericardial effusions requiring drainage
rare but serious cases of sirolimus-related pulmonary toxicities have been described

B. Everolimus

less biopsy-proven rejection
less CAV

Immunosuppression -- Drug Complications

CAV -- general

Cardiac Allograft Vasculopathy -- General

•After the first few years following transplantation, CAV is a leading cause of death and the cause of significant morbidity

•The prevalence of angiographically detectable disease approaches 50% to 60% at 5 years, and the prevalence of disease detected by intravascular ultrasonography or at autopsy is even greater

•CAV changes over time

•Early CAV is characterized by diffuse and distal involvement

•Later-onset coronary artery disease is more proximal, focal, and eccentric

Dx and Presentation

•The heart is denervated at the time of transplant and reinnervation is generally incomplete

•Vasculopathy generally progresses silently

•Silent myocardial infarction, sudden death, and progressive heart failure are common presentations. Symptoms associated with exertion, such as dyspnea, diaphoresis, gastrointestinal distress, presyncope, or syncope, are often infrequent, atypical, and may be misleading

•Early diagnosis must be made by screening studies rather than waiting to evaluate symptoms

•The most common screening approach is yearly coronary angiography

•Dobutamine stress echocardiography is a reasonable substitute for screening coronary angiography after five years post-transplant or if renal dysfunction substantially increases the risk of contrast nephropathy

•The angiographic incidence of transplant vasculopathy is 2 to 28 percent at one year and 40 to 70 percent at five years after cardiac transplantation. Late onset appears to be uncommon

•Only 7 percent had severe coronary disease, which was defined as left main coronary artery stenosis >70 percent, stenosis of two or more primary coronary arteries >70 percent, or branch stenosis in all three systems >70 percent

•Patients with angiographically significant transplant vasculopathy or severe intimal thickening on IVUS have high rates of mortality [2-5] and nonfatal cardiac events

Histologically

•CAV is characterized by proliferation and migration of smooth muscle cells

•proliferation and migration of macrophages

•intact elastic lamina

•increased ground substance and foam cells

•and macrophage-engulfed cholesterol

CAV -- Prevention and treatement

Various risk factors have been identified

•older donor hearts
•The more common risk factors for native coronary artery disease (e.g., hypertension
•diabetes

•cigarette use

•hyperlipidemia
•hyperhomocysteinemia
•low folate and vitamin B6 concentrations
•More HLA mismatches
•CMV infection
•Antibody-mediated and acute cellular rejection

RECOMMENDATIONS — The following strategies are directed at both prevention and treatment of vasculopathy

•Statin therapy — All heart transplant recipients should be treated with a statin (unless contraindicated) to reduce the incidence of both transplant vasculopathy and mortality (figure 2 and figure 3) [7-10]. The choice of drug, dosing regimen, drug interactions, and goal LDL cholesterol are inidividual

•Everolimus and sirolimus — Everolimus and sirolimus reduce the risk of rejection and transplant vasculopathy [13,15]. However, due to concerns regarding potentiation of calcineurin inhibitor-induced renal dysfunction and other side effects, these drugs are not currently approved in the United States for prevention of transplant vasculopathy in de novo heart transplant recipients. Impairment of wound healing, at least with sirolimus, makes this drug unattractive for use in de novo recipients.

•In patients who have documented vasculopathy, sirolimus should be considered since it may reduce the incidence of major adverse cardiac events. In such patients -- maintain CNI, and give proliferation-signal inhibitor in place of antiproliferative agent (purine sysnthesis inhibitor).

•Other

•Clear evidence of benefit from diltiazem is not available. Nevertheless, we suggest consideration of diltiazem therapy in the early posttransplant period, especially in patients with concomitant hypertension. (See 'Diltiazem' above.)

•PCI with stenting or atherectomy should be performed in patients with discrete lesions amenable to these approaches who have an abnormal stress test or symptoms suggestive of myocardial ischemia. (See 'Percutaneous coronary intervention' above and "Natural history and diagnosis of cardiac transplant vasculopathy".)

•Retransplantation should be considered in patients with diffuse, three vessel coronary artery disease, decreased left ventricular function, and symptoms of heart failure or angina who have no contraindications to this procedure

•Intravascular ultrasonography predicts the development of angiographic coronary artery disease and is predictive of morbidity and mortality

VAD - axial flow

Adjusting pump speedDetermine Low End of Speed Range: Start with current speed and lower until AV opens with each beat and no heart failure symptomsDetermine High Speed RangeGradually increase speed until septal flattening is demonstrated in parasternal long axis or apical 4 chamber view. Pump output should simultaneously increase and filling pressures should decrease

Determine Optimal Speed

Anticoagulation for axial-flow VAD

No postop heparin

ASA 81 - 325 mg daily

INR 1.5 - 2.5

Axial flow VADs Are associated with less

RV dysfunction

Pulmonary hypertension

and with

Equivalent cardiac output and patient functionality

VAD -- general

Type	Flow	Valves	Operating Mode
Volume Displacement	Pulsatile	Yes	Fill-to-empty or fixed
Axial	Continuous	No	Fixed speed
Centrifugal flow	Continuous	No	Fixed speed

Heartmate XVE

Pulsatility inversely proportional to pump rotation speed

Uni-ventricular support

Less suitable for small patients

More difficult implantation

Greater mobility

Discharge potential

Heartmate II

Extracorporeal VADs

Bi-Ventricular support

All patient sizes

Prompt placement

Decreased Mobility

Limited Duration

VAD Implantation Criteria

Patient Selection for VAD ImplantationIndications

NYHA functional class IV symptoms
Life expectancy < 2 years*
Not a candidate for heart transplantation*

Failure to respond to optimal medical management for at least 60 of the last 90 days*
Left ventricular ejection fraction < 25%*
Refractory cardiogenic shock or cardiac failure†
Peak oxygen consumption < 12 mL kg1 min1 with cardiac limitation
Continued need for intravenous inotropic therapy limited by symptomatic hypotension, decreasing renal function, or worsening pulmonary congestion*
Recurrent symptomatic sustained ventricular tachycardia or ventricular fibrillation in the presence of an untreatable arrhythmogenic substrate
Body surface area > 1.5 m2*‡

Relative contraindications

Age > 65 years, unless minimal or no other clinical risk factors
Chronic kidney disease with serum creatinine level > 3.0 mg/dL
Severe chronic malnutrition (BMI < 21 kg/m2 in males and < 19 kg/m2 in females)
Morbid obesity (BMI > 40 kg/m2)
Mechanical ventilation
Severe mitral stenosis or moderate to severe aortic insufficiency, or uncorrectable mitral regurgitation

Contraindications

Potentially reversible cause of heart failure
High surgical risk for successful implantation
Recent or evolving stroke
Neurological deficits impairing the ability to manage device
Coexisting terminal condition (eg, metastatic cancer, cirrhosis)
Abdominal aortic aneurysm > 5 cm
Biventricular failure in patients older than 65 years
Active systemic infection or major chronic risk for infection
Fixed pulmonary or portal hypertension
Severe pulmonary dysfunction (eg, FEV1 < 1 L)
Impending renal or hepatic failure

Multisystem organ failure
Inability to tolerate anticoagulation
Heparin-induced thrombocytopenia
Significant underlying psychiatric illness or lack of social support that may impair ability to maintain and operate VAD

VAD -- indicators of good RV function

(mean PA - CVP) X SV

Criteria for good RV function

RVSWI > 600 mmHg/ml/sq. m.

CVP < 16 or > 5 mmHg below PA wedge

PVR < 4 wood units, TPG < 15

VAD -- Intermacs Criteria

INTERMACS Patient Profiles and Timing of Mechanical Circulatory Support*Patient Profile† Patient Characteristics Time Frame Until Intervention

Pulmonary Hypertension -- Classification

1 Pulmonary arterial hypertension (PAH)

•Idiopathic

•Heritable

•Unknown

•Drugs and toxins induced

•Associated with (APAH)

•Connective tissue diseases

•HIV infection
•Portal hypertension
•Congenital heart disease
•Schistosomiasis
•Chronic hemolytic anemia
•Pulmonary veno-occlusive disease and/or pulmonary capillary hemangiomatosis

2 Pulmonary hypertension due to left heart disease

hypoxia4 Chronic thromboembolic pulmonary hypertension5 PH with unclear and/or multifactorial mechanisms

•Haematological disorders: myeloproliferative disorders,splenectomy

•Systemic disorders: sarcoidosis, pulmonary Langerhans cell histiocytosis, lymphangioleiomyomatosis, neurofibromatosis, vasculitis
•Metabolic disorders: glycogen storage disease, Gaucher disease, thyroid disorders
•Others: tumoral obstruction, fibrosing mediastinitis, chronic renal failure on dialysis

Pulmonary Hypertension -- Classification -- Hemodynamics

Pulmonary Hypertension -- Hemodynamics, WHO Class

Normal TPG < 7

PAH

PVH

Mixed

PASP

> 35

> 35

mPAP

> 25

> 25

mPCWP

< 15

> 15

> 15

PVR

> 3

< 3

>3

Class	Symptoms and activity
Class I	No limitation of physical activity
Class II	Slight limitation of physical activity, with dyspnea, fatigue chest pain, near syncope occurring with ordinary physical acivity
Class III	Marked limitation of physical activity, with dyspnea, fatigue chest pain, near syncope that occur with less than ordinary exertion
Class IV	Unable to carry out any activity without sx, which are present at rest. RH failure present

Pulmonary Hypertension -- caused by drugs

Pulmonary Hypertension -- General Rx

Predictors of a poor prognosis in iPAH

•6MWT < 300 m

•Peak VO2 < 10.4 ml/kg/min

•RAP > 20

•CI < 2

•WHO class IV sx or rapidly progressive sx

•High BNP or NTproBNP

General

•Physical activity
•Pregnancy, birth control, and post-menopausal hormonal therapy
•30 - 50% mortality with pregnancy in PAH pts
•Travel: in-flight O2 2L/min
•Psychosocial support
•infection prevention
•7% deaths from pneumonia
•Flu shots, pneumovax
•Elective surgery
- •Epidural better than general

Supportive

•Anticoagulants
•Diuretics
•O2
•When pO2 < 60, wear O2 for > 15 hrs/day
•No proof mortality is improved
•Digoxin for arrhythmias

Pulmonary Hypertension -- Specific Rx for PAH

Specific Drug Rx (PAH pts only)

Definition of Vasoreactivity

•        Decrease in mPAP by > 10

•        Decrease of mPAP to < 40

•        CO does not worsen

•        10% patients with PAH show vasoreactivity and may respond to CCB

CCB

•        Start if vasoreactivity demonstrated. Patients who have not undergone a vasoreactivity                 study or those with a negative study should not be started on a CCB because of potential                 severe side effects (e.g. hypotension, syncope, and RV failure)

•        Continue if sustained response (Improvement to WHO FC 1 -2)

Prostanoids

•        Epoprostenol

•        Continuous IV infusion only

•        improves symptoms, exercise capacity, and haemodynamics in both clinical conditions,                 and is the only treatment shown to improve survival in IPAH in a randomized study

•        Also effective in CTEPH

•        Iloprost

•        IV, inhaled and oral

•        IV as effective as epoprostenol

•        Inhaled form improves sx cf. placebo

•        Oral form not studied

Phosphodiesterase type-5 inhibitors

•        Sildenafil

•        Effective for sx in pts with IPAH, APAH (CTD and CHD) and CTEPH

•        Approved dose 20 mg tid

•        Durable effect up to a year demonstrated only with 80 mg tid

Endothelin receptor antagonists

Bosentan

•        An oral active dual endothelin-A and endothelin-B receptor antagonist

•        First molecule of its class to be synthesized

•        Evaluated in PAH (idiopathic, associated with CTD, and Eisenmenger’s syndrome)

•        Five RCTs (Pilot, BREATHE-1, BREATHE-2, BREATHE-5, and

•        EARLY) have shown improvement in exercise capacity, functional class, haemodynam                ics, echocardiographic and Doppler variables, and time to clinical worsening

•        Approved for use in PAH patients in WHO-FC II and also in patients with PAH associat                ed with congenital systemic-to-pulmonary shunts and Eisenmenger’s syndrome

Pulmonary Hypertension -- Algorithm for Specific Rx

Pulmonary Hypertension -- due to Congenital HD

•Avoid strenuous exercise

•Pregnancy should be discouraged, and contraception is indicated.

•Long-term home O2 therapy may improve symptoms, but has not been shown to modify survival
•The use of oral anticoagulant treatment in Eisenmenger’s syndrome is controversial: a high incidence of PA thrombosis and stroke is reported but there is also an increased risk of haemorrhage and haemoptysis.
•Secondary erythrocytosis is beneficial for adequate O2 transport and delivery, and routine phlebotomy should be avoided. If symptoms of hyperviscosity are present, phlebotomy with isovolumic replacement should be performed, usually when the haematocrit is > 65%
•Iron deficiency should be corrected
•No clear data support the use of CCBs in patients with Eisenmenger’s
• empirical use of CCBs is dangerous and should be avoided.
•One RCT is available with specific drug therapy: Bosentan has been shown to improve 6MWT and decrease PVR after 16 weeks of treatment in WHO-FC III patients. The long-term follow-up (40 weeks) showed sustained improvement. Bosentan is currently approved in Europe for WHO-FC III Eisenmenger’s syndrome patients

Pulmonary Hypertension -- Balloon atrial septostomy

Balloon atrial septostomy

•Pts with Eisenmenger’s syndrome, pts with IPAH with a patent foramen ovale have a survival advantage over those without

•An inter-atrial right-to-left shunt can decompress the right heart chambers, increase LV preload and CO

•Avoid Balloon atrial septostomy (BAS) in endstage pts presenting with a baseline mean RAP of > 20 mmHg and O2 saturation at rest of < 80% on room air

•Pts should be on optimal medical therapy

•Evidence suggests a benefit in pts who are in WHO-FC IV with right heart failure refractory to medical therapy or with severe syncopal symptoms

•Primary impact is on sx and 6MWT times

•The impact of BAS on long-term survival has not been established

•BAS should be regarded as a palliative procedure

Cardiology

Sunday, November 7, 2010

CHF Board Review Course

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