Trials, Hemodynamics, CP

Question 1

PARADIGM-HF Trial:

• Clinical Question
• Bottom Line

Answer 1

• CQ –>
  
  • Among patients with HFrEF, does treatment with an angiotensin receptor-neprilysin inhibitor reduce CV mortality or HF hospitalizations when compared to ACE inhibitor therapy?
• BL –>
  
  • Among patients with HFrEF, treatment with an angiotensin receptor-neprilysin inhibitor reduces CV mortality or HF hospitalization when compared to enalapril.
  • It is also associated with a reduction in all-cause mortality

Question 2

PARADIGM-HF TRIAL:

What is neprilysin?

Answer 2

• endopeptidase that breaks down vasoactive peptides (BNP, bradykinin, and adrenomedullin)
• its inhibition may lead to:
  
  • reduced remodeling
  • vasoconstriction
  • renal sodium retention
  • –> improved outcomes in HFrEF

Question 3

Paradigm-HF TRIAL:

• What was the trial preceding the Paradigm-HF trial?
• What was the major limitation of this trial and the target of the Paradigm-HF trial?

Answer 3

• OVERTURE TRIAL (2002)
• Increased rates of angioedema with omapatrilat (aminopeptidase P + ACE + neprilisyn) –> ARB + NI –> targeting multiple points in the pathophysiologic pathway and reducing angioedema

Question 4

PARADIGM-HF TRIAL (2014):

• Study design
• Major inclusion criteria
• Major outcome
• Guideline generated from study

Answer 4

• Prospective Comparison of ARNI with ACEI to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF)
• Design:
  
  • Multicenter, prospective, randomized, comparative trial - N = 8,399 with median follow up of 27 months
• Inclusion:
  
  • HFrEF (LVEF <40% and <35% were used at different points in the trial) + NYHA class II-IV symptoms randomized to ARNI vs. ACE.
• Major outcome:
  
  • ARNI had a significant reduction in CV mortality (21.8% vs. 26.5%), all-cause mortality (17% vs. 19.8%), as well as each individual component –> trial stopped early.
• Guideline:
  
  • In patients with NYHA Stage II-III HFrEF tolerating ACE inhibitor or ARB, replacement with ARNI is recommended to improve morbidity and mortality.

Question 5

What are the aldosterone antagonist trials for HFrEF demonstrate mortality benefit and dictate the guidelines?

Answer 5

• RALES (1999) - spironolactone
• EPHESUS (2003) - eplerenone

**TOPCAT (2014) - spironolactone in HFpEF

Question 6

What are the BB trials for HFrEF demonstrate mortality benefit and dictate the guidelines?

Answer 6

• MERIT-HF (1999) - metoprolol succinate
• CIBIS-II (1999) - bisoprolol
• COPERNICUS (2002) - carvedilol
  
  • COMET (2003) - carvedilol > metoprolol tartrate

Question 7

RE-LY Trial:

• Clinical Question
• Bottom Line

Answer 7

CQ –>

• Among individuals with chronic atrial fibrillation, how does dabigatran compare to warfarin in terms of stroke risk and the risk of major bleeding?

BL –>

• Compared to warfarin, high-dose dabigatran (20mg) reduces stroke risk without increasing the risk of major bleeding among patients with atrial fibrillation

Question 8

RE-LY TRIAL:

What is dabigatran?

Answer 8

• Pradaxa
• Direct Thrombin inhibitor

Question 9

RE-LY TRIAL:

• Study design
• Major inclusion criteria
• Major outcome
• Guideline generated from study

Answer 9

• Dabigatran vs. warfarin in patients with atrial fibrillation - NEJM (2009)
  
  • Randomized Evaluation of Long-Term Anticoagulation (RE-LY)
• Design:
  
  • Multicenter, parallel-group, randomized controlled trial, N=18,113, median follow up ~ 2 years
    
    • low-dose dabigatran
    • high-dose dabigatran
    • Warfarin
• Inclusion:
  
  • Nonvalvular A-fib + moderate-high risk of thromboembolic stroke
• Major outcome:
  
  • Reduced incidence of stroke compared with warfarin
• Guideline:
  
  • Approved for storke prevention in A-fib (2014)

Question 10

What are the two major axes of cardiac hemodynamic assessment?

Answer 10

• Volume status
  
  • “congestion” characterized as elevated LV filling pressure, often measured as elevated PCWP
• Adequacy of perfusion
  
  • characterized by cardiac index

Question 11

What does assessment of each axes guide in decision making:

• volume status
• adequacy of perfusion

Answer 11

• Volume status
  
  • titration of diuretics
  • suitability for, and/or tolerability of BB’s
• Adequacy of perfusion
  
  • need for inotropic agents and advanced therapies (LVAD, transplant)

Question 12

What are the noninvasive modalities for assessing cardiac hemodynamics?

Answer 12

• H&P
• Biomarkers (BNP)
• CXR
• Impedance cardiography
• Echo

Question 13

What are the invasive modalities for assessing cardiac hemodynamics?

Answer 13

• RHC
• Implantable monitors

Question 14

What are the invasive hemodynamic measurements obtained from RHC?

Answer 14

• RA
• RV
• PA
• PCWP (used as index of LV filling pressure and CO)
• CO (via Fick or TD method)

Question 15

What is the key parameter/measurement obtained in RHC?

Answer 15

PCWP

• correlates well with left atrial pressure –> usually (in the absence of mitral stenosis) is equivalent to LVEDP

Question 16

When is PCWP obtained during RHC?

Answer 16

after balloon inflation while balloon wedged in PA

Question 17

What are the two waves forms that should be identified on PCWP pressure tracing?

What should be obtained simultaneously with these tracings?

Answer 17

PCWP pressure tracings:

• A wave
• V wave

EKG tracing to compare timing and recogniation of wave forms

Question 18

CVP waveform: -a wave

Answer 18

-atrial contraction -precedes S1 -EKG: correlates with the P wave -disappears with atrial fibrillation -prominent in patients with reduced RV compliance

Question 19

Where are Canon “a” waves seen

Answer 19

• AV dissociation
  
  • RA contracts against a closed TV

Question 20

CVP waveform: -c wave

Answer 20

-Cusp of the TV, protruding backwards through the atrium as the RV contracts -EKG: Correlates with QRS

Question 21

CVP waveform: -x descent

Answer 21

-movement of the RV, descends as it contracts -downward movement –> decreases pressure in the RA -concurrent atrial diastolic relaxation, which further decreases the RA pressure -EKG: occurs before the T-wave

Question 22

CVP waveform: -v wave

Answer 22

-back pressure generated from blood filling the RA -EKG: occurs after the T-wave -Occurs just after S2 -Huge v-wave = TR *represents blood flowing back ouf of the contracting RV –> V wave would be most prominent wave, and RVSP (30 mmhg)

Question 23

CVP waveform: -y descent

Answer 23

-pressure decrease caused by the TV opening in early ventricular diastole -EKG: occurs just before the P wave -Loss of y descent = tamponade (restricted RV filling) or TS -Rapid y descent = pericardial constriction

Question 24

What are the five primary risk factors for increased risk of SCD/candidate for ICD therapy (primary prevention) in HCM?

Answer 24

• FH of premature HCM-related death, particularly sudden death, in close or multiple relatives
• Unexplained syncope, judged non-neurocardiogenic, particularly if recent, in young patients
• NSVT on serial ambulatory EKGs, particularly when bursts are multiple, repettitive, or prolonged
• Hypotensive or attenuated BP response to exercise
• Extreme LV hypertrophy (LV wall thickness > 30mm)

Question 25

What are the two risk factors for increased risk of SCD/candidate for ICD therapy (secondary prevention) in HCM?

Answer 25

* Prior cardiac arrest * Spontaneous, sustained VT

Question 26

OAT trial (2006) * Clinical Question * Bottom Line

Answer 26

CQ --\> * Among stable, high risk patients presenting with subacute myocardial infarction (3-28 days prior) with poor or absent flow of the affected artery, does late PCI + optimal medical therapy reduce mortality, MI, or NYHA class IV HF symptoms when compared to optimal medical therapy? BL --\> * Among stable, high risk patients presenting with subacute myocardial infarction (3-28 days prior) with poor or absent flow of the affected artery, late PCI + OMT does not reduce mortality, MI, or NYHA class IV HF symptoms when compared to OMT alone.

Question 27

OAT trial (2006) * Study design * Major inclusion criteria * Major outcome * Guideline generated from study

Answer 27

* Coronary Intervention for Persistent Occlusion after MI - NEJM 2006 * "Occluded Artery Trial" (OAT) * Design: * Multinational, multicenter, randomized controlled trial - N = 2,166 with mean follow up of 2.9 years * Inclusion: * Recent MI (3-28 days) --\> PCI (\< 24 hours) + OMT vs. OMT alone * Major outcome: * No significant difference in the primary outcome (composite of all-cause mortality, MI, NYHA class IV HF) * * Guideline: * Delayed PCI \>24 hours after STEMI * May be considered as part of an invasive strategy in stable patients if there is a significant stenosis in a patient infarct artery (IIb).

Question 28

What is the open artery hypothesis?

Answer 28

* suggests reperfusion of the infarct-related artery salvages myocardium and preserves LV function, thereby increasing survival

Question 29

What two trials supported the open artery hypothesis in acute MI (as well as many others)?

Answer 29

* ISIS-2 (1988) * GUSTO (1993) \*\*many others

Question 30

What is the anacrotic notch?

Answer 30

* notch in hemodynamic monitoring that falls on the upstroke and represents a sudden decrease in the rate of acceleration of pressure * usually present in AS

Question 31

What is the difference in measurement pressure measurment between catheter and Echo?

Answer 31

* Cath measures peak-to-peak pressure gradients from LVOT-Aortic outflow tract * Cath has tendency to underestimate pressure difference * Pressure recovery when some pressure is reconstituted in ascending aorta * Echo measures pressure gradient difference between LVOT and EROA * greatest pressure drop seen at EROA

Question 32

Answer 32

* Right atrial enlargement * Left atrial enlargement * NSR * Dual-chamber pacemaker (DDD), normally functioning * PM in DDD mode paces and senses in both the atrium and the ventricle, and inhibits itself from firing if intrinsic atrial or ventricular activity is recognized * Paced morphology consistent with biventricular pacing/cardiac resyncchronization * Dual ventricular pacing spikes, typically occurring within 80 msec of each other, resulting from two separate pacing leads (one in the RV and the other placed epicardially via the coronary sinus) * May result in a paced RBBB QRS morphology if the epicardial lead is being activated first (usually standard RV apical pacing results in a paced LBBB QRS morphology)

Question 33

EKG findings: * Dual-chamber pacemaker (DDD), normally functioning

Answer 33

PM in DDD mode paces and senses in both the atrium and the ventricle, and inhibits itself from firing if intrinsic atrial or ventricular activity is recognized

Question 34

EKG findings: * Paced morphology consistent with biventricular pacing/cardiac resyncchronization

Answer 34

* Dual ventricular pacing spikes, typically occurring within 80 msec of each other, resulting from two separate pacing leads (one in the RV and the other placed epicardially via the coronary sinus) * May result in a paced RBBB QRS morphology if the epicardial lead is being activated first (usually standard RV apical pacing results in a paced LBBB QRS morphology)

Question 35

What are the 3 most common causes of constrictive pericarditis?

Answer 35

* Radiation * Idiopathic * Post-cardiac surgery

Question 36

What are the presenting signs/symptoms of constrictive pericarditis?

Answer 36

* Fatigue * Exertional dyspnea * Abdominal distention, early satiety * Dramatic systemic venous congestion (peripheral edema, ascites, pulsatile hepatomegaly, JVD, pleural effusions (rare))

Question 37

What are the hallmark findings of constricitive pericarditis on jugular venous/RA tracing?

Answer 37

* Prominent X and Y descents * especially during inspiration (Kussmaul's sign)

Question 38

Answer 38

Constrictive pericarditis * rapid X and Y descents * Kussmauls sign

Question 39

What causes the dramatic X and Y descents in constrictive pericarditis?

Answer 39

exaggerated longitudinal annular motion and prominent early ventricular filling

Question 40

What are the 2D Echo/Doppler findings in constrictive pericarditis?

Answer 40

* Respiratory variation in mitral inflow ( \> 25% drop during inspiration) * Hepatic vein flow reversal during expiration * Septal "bounce" or "notch" (2D or M mode) which correlates to the time of pericardial knock on exam * must be distinguished from other septal motion abnormalities (pacing or LBBB)