Sat 830 Prutkin - Axcesor · 4/8/2015 24 Long Term Treatment Beta‐blockers‐Don’t use if delta wave Calcium channel blockers‐Don’t use if delta wave Referral to cardiology

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Jordan Prutkin, MD, MHS

5/2/2015

Goals Learn mechanism of paroxysmal SVT

Recognize SVT on an ECG

Understand workup

Determine the best acute and chronic management

Evaluate asymptomatic WPW

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Paroxysmal SVT 0.2‐0.8% of the population

More frequent in younger people with no cardiac disease

Not life threatening (usually)

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SVT symptoms Palpitations

Fatigue

Presyncope/Syncope

Chest pressure

Dyspnea

Diaphoresis

Nausea/Emesis

Neck pounding

SVT

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SVT is typically?1. Narrow complex (QRS <120 msec)

2. Wide complex (QRS > 120 msec)

Link MS. NEJM 2012;367:1438‐1448.

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Atrial Fibrillation

Atrial Flutter

Flutter waves Flutter waves

Flutter waves

Flutter waves

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AVNRT

Retrograde P waves

Retrograde P waves

AVNRT

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AVRT

AVRT vs. AVNRTAVRT AVNRT

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Wolff‐Parkinson‐White (WPW)

Delta wave

The best lead to look for WPW is?1. I

2. II

3. V1

4. V3

5. There is no best lead

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WPW

Does this show WPW?1. Yes

2. No

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Lown‐Ganong‐Levine


2. No

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SSS and Junctional Rhythm


2. No

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Ectopic Atrial Rhythm

Negative P wave

Atrial Tachycardia

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Junctional Tachycardia

P waves visible

Atrial rate > Ventricular rate

Atrial flutterAtrial tachycardia

Check RP interval

Short(RP < PR)

Long(RP > PR)

Sinus tachycardiaAtrial tachycardiaAtypical AVNRT

PJRT

RP < 70 ms RP > 70 ms

AVNRT AVRTAtypical AVNRTAtrial tachycardia

Yes (A>V) No (A=V)

NoYes

AHA/ACC SVT guidelines. JACC 2003. 42 (8):1493‐1531.

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Does it matter acutely what the SVT is?1. Yes, definitely

2. No, not really

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Case 63 year old male is admitted with chest pain

While waiting for a stress test, he reports abrupt onset of palpitations and mild chest discomfort to his nurse.

Pulse 150, blood pressure 132/88

Case Presenting EKG

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What do you do?1. Cry?

2. Call your colleague?

3. Valsalva maneuver

4. Give metoprolol?

5. Give adenosine?

6. Any and all of the above?

Case‐Adenosine

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Acute Treatment If hemodynamically unstable, cardiovert.

Hypotension

Heart failure

Chest pain with ST changes

Mental status change

SVT treatment Vagal maneuvers (with ECG)

Adenosine (with ECG)

6mg, 12mg, central line if present

Beta‐blockers/Ca channel blockers (on telemetry)

Can use even if WPW known on baseline ECG

Amiodarone (on telemetry)

Procainamide (on telemetry)

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Termination of Tachycardia

Fox et al. Mayo Clinic Proceedings. 2008;83:1400‐1411.

Adenosine‐Run a 12 lead EKG

AHA/ACC SVT guidelines. JACC 2003. 42 (8):1493‐1531.

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Preexcited Afib

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Cardioverted

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If preexcited Afib

Don’t use beta‐blockers or Ca‐channel blockers

Procainamide

Amiodarone

Ibutilide

Sedate for cardioversion

Call an expert

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What is the best test to order?32 year old male with abrupt onset and offset palpitations lasting 5 minutes at a time occurring every 10 days.

1. 24 Holter monitor

2. 30 day event monitor

3. Implantable loop recorder

Workup of SVT EKG

Holter monitor if occurring daily

Event monitor if less frequently

Echocardiogram

Consider treadmill test if the SVT is precipitated by exercise

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Event Monitor

Treadmill test

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Long Term Treatment Beta‐blockers‐Don’t use if delta wave

Calcium channel blockers‐Don’t use if delta wave

Referral to cardiology or EP

Class IC/III antiarrhythmics

Catheter ablation

Bethesda Conference‐SVT No restrictions

SVT prevented by therapy

Asymptomatic short episodes, 5‐15 seconds

Restricted

Syncope, near‐syncope, significant symptoms

Structural heart disease

Treated with no recurrence for 2‐4 weeks, 1A sports only

Ablation

If successful, can return to play in several days if repeat EP testing done

2‐4 weeks if no EP testing

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Presentation of WPW 1‐3 per 1000 persons

40% of infants will have loss of delta wave

0‐25% lose delta wave in adolescence

65% of adolescents, 40% adults are asymptomatic

Cohen et al. Heart Rhythm 2012;9:1006‐1024

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Risk of SCD

Cohen et al. Heart Rhythm 2012;9:1006‐1024

Baseline Treadmill

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Peak Exercise

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Conclusions‐SVT Get an ECG during palpitations

Don’t use hemodynamics to determine rhythm

Use adenosine or vagal maneuvers (with ECG!)

Check baseline ECG

Consider cardiology referral for SVT or asymptomatic WPW

[email protected]

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Link MS. NEJM 2012;367:1438‐1448.

Delacretaz. NEJM 2006.354:1039‐1051

Evaluation and Management of Heart Failure

S. Carolina Masri, MD

Division of Cardiology

University of Washington

Disclosures

No financial disclosures

No conflict of interest

Objectives

Frame the epidemiology of HF

Discuss evidence-based pharmacotherapies on reduced ejection fraction

Explore the utility of guideline directed medical therapies (GDMT)

At age 40, lifetime risk is 20 % in both genders

About 50% HFrEF, 50% preserved

Mortality rate 50% within 5 years

1-month readmission rate is ~25 %

Population Group Prevalence Incidence Mortality

Hospital Discharges Cost

Total population

5,700,000 670,000 277,193 990,000$39.2 billion

4

Heart Failure Epidemic in US

ACCF/AHA Guidelines 2013

Chronic Heart Failure Groups

Classification LV EF % Description

HFrEF ≤ 40 Effective therapies well-established

HFpEF ≥ 50 “Diastolic HF”, challenging diagnosis, therapies unclear

a. HFpEF, borderline

41 – 49 Intermediate group, clinically more similar to HFpEF

b. HFpEF, improved

> 40 Recovered HFrEF, not well characterized

Yancy C et al. ACCF/AHA 2013 Guidelines

100

75

50

25

0I II III IV

1

10

NYHA CLASS

Ann

ual S

urvi

val R

ate

Hos

pita

lizat

ions

/ y

ear

.1

Deceased

Adapted from Bristow, MR Management of Heart Failure, Heart Disease: A Textbook of Cardiovascular Medicine, 6th edition, ed. Braunwald et al.

Survival RateHospitalizations

Heart Failure Progression

Heart Failure Progression

New York Heart Association Functional Classification

Class I: No symptoms with ordinary activity

Class II: Slight limitation of physical activity. Comfortable at rest, but ordinary physical activity results in fatigue, palpitation, dyspnea, or angina

Class III: Marked limitation of physical activity. Comfortable at rest, but less than ordinary physical activity results in fatigue, palpitation, dyspnea, or anginal pain

Class IV: Unable to carry out any physical activity without discomfort. Symptoms of cardiac insufficiency may be present even at rest

Stages of CHF — ACC/AHA Guidelines 2005

AHigh-risk patients

Hypertension, diabetes, coronary disease, family history, cardiotoxic drugs

BStructural heart disease

LVH, MI, low LVEF, dilatation, valvular disease

C

Prior or current HF symptoms

D

Refractory

22%

34%

12%

0.2%

5 year survival Prevalence

20%

75%

96%

97%

Revised August 2005 from Jessup M, Brozena S. NEJM 2003;348:2003

Risk factor reduction, patient and family educationTreat HTN, DM, CAD, dyslipidemia. ACEI or ARB

ACEI, BB in all. Is patient candidate for surgery?Sodium restriction, diuretics

Aldosterone antagonistsDigoxin

InotropeVAD, TX

Stage AHigh riskwith no

symptoms

CRT, ICD if applicable

Stage BStructural

heart disease,

no symptoms

Stage CStructuraldisease,prior orcurrent

symptoms

Stage DRefractorysymptomsrequiring special

intervention

Stages & steps: treatment of systolic HF

Hospice

Brief inotrope

ACEI, ARB’s if intolerant of ACEI, BB if MI or low LVEF

(#1) 75 year old man with non-ischemic CM is admitted tooutside hospital. BNP on admission is 500 pg/mL. He istransferred immediately to your institution for furthermanagement. NT-proBNP at your hospital the following dayis 2300 pg/mL. Which of the following is true?

a) His clinical condition has worsened since his initial

presentation

b) The BNP and NT-proBNP values are approximately

Equivalent

c) Natriuretic peptide levels are not useful in the elderly

d) None of the above

Structure and Cleavage of NT-proBNP/BNP

T ½ = 2 hours T ½ = 22 minutes

Both digested by NEPs and cleared renally

NT-ProBNP vs BNP

NT-ProBNP values between 5-10 times BNP value in same patient

Both are affected by age (NT-ProBNP more)

Both affected by renal function

BNP and diagnosis of HF: Breathing Not Properly Trial

Dyspneic patients in the ED setting

ROC for BNP was 0.91, more accurate than H+P findings

Cutpoint of 100 pg/mL for all pt: Sensitivity 90%, specificity 76%

Maisel et al. N Engl J Med 347:161-167, 2002

Conditions that Influence BNP Concentrations

Increased BNP

Age (older)

Sex (female)

Renal dysfunction

MI/ACS

Right-sided heart failure (corpulmonale, PE)

High output failure (cirrhosis,septic shock)

Decreased BNP

ObesityEarly acute heart failure (less than 1 hr)

Heart Fail Rev 8:327-334, 2003.

Logeart et al, JACC 2004

Death or hospitalization after admission stratified by pre-discharge BNP

BNP/NT-proBNP

Heart Failure Pathophysiology

Myocardial injury (CAD, HTN, CM, Valvular disease)

Fall in LV performance ↑ wall stress

Activation of RAAS, SNS and Cytokines

Morbidity and Mortality

Peripheral vasoconstrictionHemodynamic alterations

Heart Failure symptoms

ANPBNPANPBNP

Remodeling and Progressive worsening

of LV function

Myocardial Toxicity

Goals in the Management of Heart Failure

Stabilize the patient –

– Make the patient feel better

Stabilize the disease process

– Keep the patient alive, out of the hospital, and feeling better

(#2) Ms LA is a 62 year old female with systolic heart failure LVEF 32 % in CF II of NYHA. She becomes an expert on HF management from reading wikipedia. She is wondering which of the following will improve her chance of survival?

a) β-blocker, ACE-I, aldosterone antagonists

b) β-blocker, ACE-I, aldosterone antagonists, diuretics

c) β-blocker, ACE-I, aldosterone antagonists, digoxin

d) All of the above

e) None of the above

Diuretics

Used to relieve fluid retention and treat symptoms

Diuretics do NOT decrease mortality

In fact, observational studies have shown association of higher doses with worse survival

Sodium Reabsorption Sites in the Nephron

Proximal Tubule

70%Distal Tubule

20%

5%

1-4%

Loop of Henle

Collecting

Tubule

Glomerulus

Thiazide Diuretics

Loop Diuretics

Mineralocorticoid

Receptor antagonist

Bioavailability of Loop Diuretics

100%

80%

50%

10%

-

-

-

furosemide torsemide bumetanide

Additional points about diuretics

1 mg Bumetanide= 20 mg torsemide = 40 mg furosemide

Furosemide PO to IV conversion is 2:1

Bumetanide and torsemide PO to IV conversion are 1:1

Consider ethacrynic acid if true allergy to loop diuretics

Sulfa moiety in antibiotics is not the same as loop diuretics

Diuretics: Guideline-Based Recommendations

Indication To improve symptoms in fluid overload

Considerations wheregreater diuresisneeded.(Diuretic refractoriness)

Increased dose – 2 or 3 times daily dosing provides more diuresisConsider switch to oral torsemide/bumetanide if persistent fluid retention despite high dose of furosemideConsider adding chlorothiazides or metolazone.Try to avoid chronic daily metolazone use: high potential for electrolyte imbalance and volume depletion.Intravenous administration

Monitoring BMP, symptomatic hypotension, renal dysfunction, especially with high dose and combination use.

When treatment goalachieved

Consider dose reduction or even discontinuation if improved clinical status

Monitor carefully for recurrent fluid retention.

Patient education Weight and fluid monitoring Selected patients may adjust dose to weight / clinical change

ACCF/AHA 2013: Common DiureticsDrug Initial Dose Max Dose Duration of Action

Loop Diuretics

Bumetanide 0.5-1.0 mg 1-2x/d 10 mg 4-6 h

Furosemide 20-40 mg 1-2x/d 600 mg 6-8 h

Torsemide 10-20 mg 1x/d 200 mg 12-16 h

Thiazide Diuretics

Hydrochlorothiazide 25 -100 mg 1-2x/d 200 mg 6-12 h

Metolazone 2.5-10 mg with loop diuretic 20 mg 12-24 h

Chlorothiazide (IV) 500 mg with loop diuretic N/A N/A

K-sparing Diuretics

Amiloride 5 mg 1x/d 20 mg 24 h

Spironolactone 12.5-25.0 mg 1x/d 50 mg 1-3 h

Triamterene 50-75 mg 2x/d 200 mg 7-9 h

Adapted from: Yancy C et al. ACCF/AHA 2013 Guidelines

(#3)-Your patient Mr G has recently been discharged from the hospital on lisinopril 10 mg bid, furosemide 40 mg qd and low doses of carvedilol 6.25 mg bid. On his visit to the clinic one week after dismissal, he reported feeling well, able to climb 2 flights of stairs, no PND or orthopnea. His weight has been stable, no swollen of LE.

VS: BP: 110/60 mmHg, HR: 78 bpm ,reg rhytm

PE: No JVD, no gallop, CTA bilaterally, no peripheral edema, warm and well perfused. Normal mentation

Labs: Creatinine: 1.7 mg/dl ( prior to discharged was 1.3 mg/dl)K: 4.9 mEq/LBNP: 250 pg/ml upon admission was 1040 pg/ml

(#3)-Cont’dThe most appropriate step at this point include which of the following?

a)Discontinue treatment with lisinopril and start with

hydralazine/isosorbide dinitrate.

b)Discontinue treatment with lisinopril and start with candesartan

c)Decrease the doses to half of lisinopril

d)Continues with the same treatment

RAAS Pathway: ACE-I

Angiotensinogen

Non-ACE pathways(eg, chymase)

Vasoconstriction Cell growth Na/H2O retention Sympathetic activation

Renin Angiotensin I

Angiotensin II

ACE

Cough,angioedema

Benefits? Bradykinin

Inactivefragments

Vasodilation Antiproliferation

(kinins)

Aldosterone AT2

AT1

ACEI in Chronic Heart FailureJAMA 1995;273:1450

Metanalysis - ACEi trials in Heart Failure N~7,500 patients

Death 23%

Death/HF Hosp 35%

Heart Failure Death 31%

Sudden Death 9%

Reinfarction 18%

Selected ACE-I Trials: Mortality

Low vs.High dose

ACE-I vs.ISDN/Hydra

Class I* Benefit forhospitalizationTrend for ACM;Low backgroundmortality; 12 yearf/u significant

CONSENSUS SOLVDTreatment

SOLVDPrevention

VHeFT II ATLAS

N 253 2569 4228 804 3164

LVEF Not reported < 35% < 35% < 45% < 30%

NYHA IV II-IV I I-IV II-IV

ACE-I Enalapril Enalapril Enalapril Enalapril Lisinopril 32.5-35 mg

Mortality in comparator

36% in placebo arm at 12 mo



25% in HYD/NIT armat 24 mo

42% in Lisinopril 2.5-5 mg at 46 mo

RRR 31% 16% No difference 28% No difference

Adapted from: Griffin BP et al. Cleveland Clinic Cardiology Board Review

When to Use ACE Inhibitors?

All HF patients with LVEF <40% should be treated with an ACE-I and a beta-blocker, unless a specific contraindication exists

(Class I, Level A)

Jessup et al, Circulation 2009

Optimal Dosing of ACE Inhibitors

• General Guideline:

• Start low and titrate to the target dose used in the clinical trials or the MAXIMUM TOLERATED DOSE(ATLAS trial)

• Captopril 6.25-12.5 mg 50 mg BID-TID (SAVE)

• Enalapril 2.5 mg BID 20 mg BID (SOLVD/X)

• Ramipril 2.5 mg BID 5 mg BID (AIRE/EX)

• Lisinopril 2.5-5 mg QD 30-40 mg OD (GISSI 3)

• Trandolapril 1mg 4 mg (TRACE)

ACE – Pearls

Up to 85-90% tolerate ACEIs

Start with low dose, especially in elderly

Follow-up BMP in 1-2 weeks

Titrate/double dose to target every 1-2 weeks

Bedtime dosing once BB introduced

Most ACEIs now on $ 4 generic lists

Remember some ACE inhibitor is better than no ACE inhibitor

ACEI or ARB - pearls

Worsening renal function

10% to 30% creatinine can be anticipated with ACE -and it is not an indication to discontinue treatment:

Avoid sodium and volume depletion Reduce diuretic dose Fluid resuscitation, salt liberalization Avoid NSAIDs

Hyperkalemia

Incidence ~ 3-10%, [K+] > 5.5 mEq/L

Drug Interactions: NSAIDs, KCL supplements,

Additional considerations: ACE-I

ACE-I can cause angioedema

Bilateral RAS is a contraindication to ACE-I

AVOID during pregnancy

Can increase bradykinin, resulting in cough

Generally used as 1st line therapy due to vasodilation even during ADHF

Inability to tolerate ACE-I is a bad prognostic sign

RAAS Pathway: ARB

Angiotensinogen

Non-ACE pathways(eg, chymase)

Vasoconstriction Cell growth Na/H2O retention Sympathetic activation

Renin Angiotensin I

Angiotensin II

ACE

Cough,angioedema

Benefits? Bradykinin

Inactivefragments

Vasodilation Antiproliferation

(kinins)

Aldosterone AT2

AT1

ARB in Heart Failure

Questions

Alternative to ACEI ?

Better than ACEI ?

Added to ACEI ?

Granger CB, et al. Lancet. 2003;362:772-776.

CHARM-Alternative: ARB vs. Placebo

Number at risk

Candesartan 1,013 929 831 434 122

Placebo 1,015 887 798 427 126

0 1 2 3Years

0

10

20

30

40

50

Placebo

Candesartan (intolerant of ACE-I)

HR 0.77 (95% CI 0.67-0.89), P=.0004Adjusted HR 0.70, P<.0001

3.5

406 (40.0%)

334 (33.0%)

Pro

po

rtio

n W

ith

CV

Dea

th

or

CH

F H

osp

ital

izat

ion

(%

)

Primary outcome of CV death or CHF hospitalization

ARB vs. ACE-I

No clear difference between ACE-I and ARB, with some trials favoring ARB, and others trending toward ACE-I superiority

ARB in addition to ACE-I

ARB added to ACE-I had no impact on all-causemortality in any of the major cardiovascular trials

ACEI/ARBs : Low vs Higher doses

Higher doses HF hospitalizations > Death

ATLAS - Lisinopril 5 vs 35 mg 24% vs. 8%HEAAL - Losartan 50 vs 150 mg 13% vs 6%

ARBs Doses in HF

ARBs

Candesartan 4-8 mg qd 32 mg qd 24 mg/day

Losartan 25-50 mg qd 150 mg qd 129 mg/day

Valsartan 20-40 mg bid 160 mg bid 254 mg/day

Starting HF doses! Target HF doses! Mean doses achieved in trials!

Mineralocorticoids receptors antagonist

Direct aldosterone antagonism in LV remodeling:

Decreased local fibrosis

Increased local dilation via increased NO

Decrease cardiac NE release, SCD

Benefits in 1-3 months

Spironolactone

Placebo

Months

RR = 0.70P < 0.001

Pro

bab

ility

of

Su

rviv

al

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 12 24 36

Epleronone

Placebo

RR = 0.85P < 0.008

0.40

0.50

0.60

0.70

0.80

0.90

1.00

0 12 24 36

Months

RR = 0.78P = 0.014

MRAs Beneficial in HFrEF and Post-MI LVD

30% Risk Reduction 15% Risk Reduction

0 12 24 36

0.50

0.70

0.80

0.90

0.40

1.00

0.60

Epleronone

Placebo

22% Risk Reduction

RALES(Severe HFrEF)

EPHESUS(Post-MI)

EMPHASIS(Mild HFrEF)

Reviews of Mechanisms : Pitt Heart Fail Rev 2012; Kamalov,…,Weber JCV Pharm 2013

Pitt NEJM 1999 Pitt NEJM 2003 Zannad NEJM 2011

Months

When to use aldosterone blockers?ACCF/AHA 2013:

-Recommended for NYHA class II-IV HF with LVEF ≤ 35%.

-After acute MI with LVEF ≤ 40% or history of diabetes

Contraindications

SCr > 2.5 men, SCr > 2.0 women (eGFR < 30 ml/min)

Acute renal insufficiency Hyperkalemia, K+ > 5

Aldosterone Blockers Pearls

Decrease mortality by 15-30%

Start low spiro/eplerenone 12.5-25 mg/day.

Target doses 25-50 mg/day.

• Follow-up BMP after initiation, dose change:

3 days then,1 week then,monthly for 3 months then,

Every 3 months indefinitely

Eplerenone is generic $28/month at UWMC Pharmacy

– Less Gynecomastia 1% vs. 10%

– Less impotence

(#4)You are asked to evaluate a 60 year old woman AAwho is admitted for treatment of cellulitis. She is doing well , but nurses has been refusing to administer her lisinopril and carvedilol due to low blood pressure. She has stable NYHA Class II symptoms. She is not lightheadedness. Her BP usually range of 75/50-80/55 mmHg. Her LVEF is 28 %.

Meds:Lisinopril 20 mg qd, Carvedilol 12.5 mg bid, furosemide 20 mg qd, Spironolactone 12.5 mg qd

VS: BP: 80/50 HR : 66 bpm regular

PE: No JVD, no gallop, CTA bilaterally, no peripheral edema, warm and well perfused. Normal mentation

(#4)-Cont’dWhich one of the following represent the most appropriate next step?

a)Hold the lisinopril and carvedilol completely

b)Reduce the doses of lisinopril and carvedilol by half and

follow up with the cardiologist as outpatient

c)Discontinue lisinopril and start hydralazine/isordil

d)Continues same doses of lisinopril and carvedilol

How Do Beta Blockers Improve Heart Failure?

Reverse LV remodeling, adrenergic receptors

Reduces risk of sudden cardiac death

Benefits in 3-6 months

Contraindications:

Severe bronchospastic disease

Severe, unpaced, symptomatic bradycardia HR < 50

Unpaced 2nd or 3rd degree AV Block

Effect of Beta Blockade on Outcome in Patients With HF and Post-MI LVD

BB in HFrEF

Drug Starting HF

Doses Target HF Doses

Mean Dose Achieved in

Trials

Bisoprolol 1.25 mg qd 10 mg qd 8.6 mg/day

Carvedilol 3.125 mg bid (with food)

25 mg bid (<85 kg) 50 mg bid (>85 kg)

37 mg/day

Carvedilol CR 10 mg qd 80 mg qd n/a

Metoprolol Succinate CR/XL

12.5-25 mg qd 200 mg qd 159 mg/day

BB -Recommendations

General Recommended for symptomatic and asymptomatic patients with reduced LVEF (≤ 40%) to reduce M&M.

Initiation; Dosing;

Initiate at low dosesUp-titrate gradually, generally ≥ 2 week intervals

Target doses shown to be effective in clinical trials

Target dose in 8-12 wks;Maintain at maximum tolerated dose

Beta Blockers -Pearls

If symptoms worsen or side effects appear

Adjust dose of diuretic Continue titration to target dose once symptoms at baseline.

If an acute exacerbation of chronic HF occurs

Maintain therapy if possible.Reduce dosage if necessary.Avoid abrupt discontinuation.If discontinued or reduced, reinstate gradually before discharge

Following decompensation

Initiate after optimizing volume status and discontinuation of intravenous inotropic agents.

Whenever possible, initiate prior to hospital discharge in stable patients.

Should we increase ACE-/ARB to target doses before beginning BB?

Titrating to target doses provides more benefit than very low doses.

However, the difference in efficacy between intermediate and high doses is small.

Thus, not unreasonable to start β-blockers after intermediate doses of ACEI are achieved, or vice versa.

Do not reduce or discontinue ACEI or β-blockers for asymptomatic low BP measurement

Hydralazine and Nitrates

Rationale is to reduce preload and afterload by both venous and arterial vasodilation

Hydralazine is predominately an arterial vasodilator

Nitrates are mostly venodilators

Increases NO bioavailability since nitrates are NO donors and hydralazine may have antioxidant effects

What about Hydralazine and Isordil? The A-HeFT Trial

1050 NYHA III/IV AA pts

LVEF < 35%

Composite endpt (death, HF hosp, QOL), Terminated early

– Hyd 75/Isordil 40 TID

– Mean - Hyd 142/Isordil 76

– ACE/ARB 86%

– BB 74%

– Spiro 39%

– Digoxin 59%

Ann Taylor et al.NEJM 2004;351:2049-57

Mortality 43%, p=0.02Do non-black patients benefit from hydralizine/nitrates?

Su

rviv

al %

Days Since Baseline Visit

43% Decrease in Mortality

Fixed Dose ISDN/HDZN

Placebo

P = 0.01

85

90

95

100

0 100 200 300 400 500 600

Hydralazine-Nitrate Combination -Guideline-Based Recommendations

Medical Therapy for Stage C HFrEF: Magnitude of Benefit Demonstrated in RCTs

GDMTRR

Reduction in Mortality

NNT for Mortality Reduction

(Standardized to 36 mo)

RR Reductionin HF

Hospitalizations

ACE - or ARB 17% 26 31%

Beta blocker 34% 9 41%

Aldosterone antagonist

30% 6 35%

Hydralazine/nitrate 43% 7 33%

Pharmacotherapy: Digoxin The oldest cardiac drug still in contemporary use

• Inhibits Na-K ATPase increases contractility

• Neurohormonal effects decreased SNS activation, vagomimetic Slows AV conduction

Digoxin: DIG Trial (NEJM 1997)

Reduces hospitalization

But does NOT reduce mortality

Narrow therapeutic window : Digoxin level should be < 1.0 (0.5 to 0.9) ng/mL

Monitor closely for digoxin toxicity

Renewed interest in certain subgroups? Subanalyses suggest that sicker patients may have additional benefit (EF < 25%, NYHA III-IV)

Vincent van Gogh’s yellow period and digitalis

Starry nightDr. Gachet at a Table with Sprig of Foxglove

Digoxin Toxicity

Symptoms: Fatigue, anorexia, diarrhea, yellow halos, confusion, agitation

Classic arrhythmias seen with toxicity:

- Paroxysmal atrial tachycardia w/ block

- Accelerated junctional rhythm

- Bidirectional ventricular tachycardia (only dig and CPVT can do this)

Electrolyte abnormalities that predispose to dig tox:

- Low Mg, Low K, High Ca

PARADIGM HF – Valsartan-LCZ696 NEJM 2014

PARADIGM HF – Valsartan-LCZ696NEJM 2014

Composite 20%

CV death 20%

HF Hosp 21%

Mortality 16%

First medication to replace a HF medication (ACEI)

Enalapril 10 mg BID vs. Valsartan-Neprilysin 200 mg BID in 8442 patients NYHA 2-4, EF ≤ 35%, BNP >150 or >100 if HF Hospitalization <12 months. On ACEI/ARB with SBP ≥100 and eGFR>30.

F/U 27 months

Evidence-Based Treatment for Heart Failure with Reduced LVEF

Control VolumeReduce Mortality

Sodium Restriction*Diuretics*

Digoxin*

-BlockerACEIor ARB

AldosteroneAntagonist

Treat Residual SymptomsCRT

an ICD*Hyd/ISDN*

*For select indicated patients.

ICD*

Treat Comorbidities

Aspirin*Warfarin*

Statin*

Enhance Adherence

EducationDisease Management

Performance Improvement Systems18

Potential Impact of Optimal Implementation of Evidence-Based HF Therapies on Mortality

Fonarow GC, et al. Am Heart J 2011;161:1024-1030.

Guideline Recommended

Therapy

HF Patient

Population Eligible

for Treatment, n*

Current HF

Population

Eligible and

Untreated, n (%)

Potential Lives

Saved per Year

ACEI/ARB 2,459,644 501,767 (20.4) 6516

Beta-blocker 2,512,560 361,809 (14.4) 12,922

Aldosterone Antagonist 603,014 385,326 (63.9) 21,407

Hydralazine/Nitrate 150,754 139,749 (92.7) 6655

CRT 326,151 199,604 (61.2) 8317

ICD 1,725,732 852,512 (49.4) 12,179

Total - - 67,996

Improved Adherence to ACC/AHA HF Guidelines Translates to Improved Clinical Outcomes in Real World HF Patients

Each 10% improvement in ACC/AHA guideline-recommended composite care was associated with a 13% lower odds of 24-month mortality (P<0.0001)

Fonarow GC, et al. Circulation. 2011;123:1601-1610.

Case# 56 y/o male caucasian admitted in 10/2014 because of AHF. Normal coronary arteries and cardiac MRI without evidence of acute myocarditis and or infiltrative disease

Echocardiogram 10/14 Echocardiogram 3/15

Meds: Metoprolol XL 200 mg qd, Lisinopril 20 mg qd, Spironolactone 12.5 mg qd, Now off diuretics

Conclusions

HF remains common and costly in the current era, with increasing incidence and prevalence

Heart failure medications can reduce mortality by 60-70%

Effort should be made to implement guideline-recommended therapies in HF patients in absence of contraindications or intolerance

High risk patients Inability to tolerate or need to withdraw HF medications

Low BP, Sodium

High Diuretic dose, BUN, Creatinine, BNP

Recurrent hospitalizations

Thank you for your attention!

ARB vs. ACE-I

No clear difference between ACE-I and ARB, with some trials favoring ARB, and others trending toward ACE-I superiority

ELITE I ELITE II OPTIMAAL VALIANT

N 722 3152 5477 9818

Admission criteria

EF < 40%NYHA II-IVAge > 65 y

EF < 40%NYHA II-IVAge > 60 y

MI w/ anterior Q waves or clinical HF or EF < 35% or LVEDD > 65 mm

EF < 40% or clinical HF

Ischemic etiology

68% 79% 100% post-MI 100% post-MI

ARB Losartan Losartan Losartan Valsartan

Comparator Captopril Captopril Captopril Captopril

Mortality 46% RRR at 12 mo

No difference at18.2 mo




ARB in addition to ACE-I

ARB added to ACE-I had no impact on all-cause mortality in any of the major cardiovascular trials

ValHEFT CHARM Added VALIANT

N 5010 2548 9794

LVEF < 40% < 40% < 40% or clinical HF

NYHA II-IV II-IV I-IV

Ischemic etiology

57% 62% 100%

ARB Valsartan Candesartan Valsartan

ACE-I use 93% on ACE-I 100% on ACE-I 100% on captopril

Mortality No difference at 23 mo

No difference at41 mo



Carvedilol vs Metoprolol Succinate

Usefulness of Torsemide after Admission for ADHF

234 pts admitted for ADHF

torsemide furosemide

52% HF Hospitalization

(Murray, et al. Am J Med 2000;111:513-521)

Randomized on Discharge

DIG Trial (NEJM 1997)

HF with EF < 45% on ACE and diuretic

N = 6800 Mean EF 28%

Mortality

Death or HF Hosp

MERIT-HF Study Group. Effect of Metoprolol CR/XL in chronic heart failure: Metoprolol CR/XL randomized intervention trial in congestive heart failure (MERIT-HF). LANCET. 1999;353:2001-07.

Severity of Heart FailureMode of Death

12%

24%

64%

CHF

Other

SuddenDeath

n = 103

NYHA II

26%

15%

59%

CHF

Other

SuddenDeath

n = 103

NYHA III

56%

11%

33%

CHF

Other

SuddenDeath

n = 27

NYHA IV

Neprilysin Inhibition Potentiates Actions of Endogenous Vasoactive Peptides That Counter

Maladaptive Mechanisms in Heart Failure

Endogenousvasoactive peptides

(natriuretic peptides, adrenomedullin,bradykinin, substance P,

calcitonin gene-related peptide)

Inactive metabolites

Neurohormonal activation

Vascular tone

Cardiac fibrosis, hypertrophy

Sodium retention

Neprilysin Neprilysininhibition

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Cardiac Stress TestingSome Useful Considerations

Zachary D. Goldberger, MD, MS, FACC, FHRSAssistant Professor of Medicine

UW School of MedicineHarborview Medical Center

Division of [email protected]

FINANCIAL OR OTHER RELATIONSHIP DISCLOSURE:

None

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What Will Be Covered

• Chest pain evaluation and risk stratification

• Stress testing modalities, pros and cons

• Special topics: costs, women, radiation

• Cases with ARS

• Q&A

• Stress testing to detect inducible ischemia has been “gold standard” noninvasive test used to diagnose CAD

• Designed to “provoke” cardiac ischemia by using exercise or pharmacological stress agents

Why Stress Test?

Increase myocardial work and oxygen demand

Induce vasodilation‐elicited heterogeneity in coronary flow

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KEY POINT:

Stress testing is a great means of diagnosing fixed obstruction

Confusing Terminology!

1. Substernal CP2. Brought on by exertion and/or emotional

stress3. Relieved with rest and/or NTG

• Typical angina: 3 features• Atypical angina: 2 features• Non‐anginal/noncardiac CP : ≤1 feature

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Snow V et al. Ann Intern Med 2004;141:57-64.

HistoryPretest Probability

Posttest Probability‐‐Most Useful for Intermediate Risk Patients

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Stress Testing Modalities

• Treadmill exercise ECG testing

• Echocardiography– Exercise

– Pharmacologic (dobutamine, adenosine)

• Radionuclide myocardial perfusion imaging (MPS)– Exercise

– Pharmacologic stressors (adenosine/regadenoson, dipyridamole, dobutamine)

– Tracers (thallium, technetium, rubidium)

Sensitivity and Specificity

Test Sensitivity Specificity

Exercise treadmill 68% 77%

Stress echocardiography

76% 88%

Myocardial perfusion imaging

88% 77%

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Which is a baseline ECG finding that could lead to uninterpretable stress ECG?

A. >1 mm ST depression

B. Left bundle branch block

C. LVH

D. Wolff‐Parkinson‐White pattern

E. All of the above

Able to Exercise

Fihn SD, et al. J Am Coll Cardiol 2012;60(24): 1‐121.

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Unable to Exercise

Fihn SD, et al. J Am CollCardiol 2012;60(24): 1‐121.

Which is the following is FALSE?

A. ST depressions on exercise ECG can identify specific location of cardiac ischemia

B. 1‐2 mm ST upsloping depressions in the inferolateral leads may be a normal variant

C. RBBB on baseline ECG can be interpretable on stress ECG

D. Imaging studies are often performed in conjunction with exercise ECG

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Exercise Treadmill Testing

• ≥ 1 mm ST depression• LBBB• Paced rhythm• Preexcitation (WPW pattern)• LVH• Digoxin use

• If baseline ECG shows secondary ST‐T wave changes, or ischemia, ETT cannot be performed

• Poor diagnostic test, good prognostic test

• Location of ST depressions are not indicative of ischemic territory

Treadmill Exercise ECG Testing

Advantages

• Low cost

• Standard treadmill assessment of ischemia, functional capacity, and prognosis

• Widely available

• Accuracy tested in different populations

Disadvantages

• Lower sensitivity

• Specificity poor with marked ST‐T abnormalities on resting ECG, digoxin use, LBBB or pacemakers, and women

• Does not localize site or extent of myocardial ischemia

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Exercise Treadmill Testing

Duke treadmill score:

Minutes on Standard Bruce Protocol

‐ 5 x (mm ST depression)

‐ 4 x (angina)

angina: 0=none, 1=typical, 2=limiting

• Score of +5 or more: 97% 5‐year survival

• Score of ‐11 or less: 72% 5‐year survival

Exercise ECGs: Beyond the STs• Exercise duration

• Onset/resolution/magnitude of symptoms/ST changes

• Impaired HR response (“chronotropicincompetence”)

• SBP with high workloads• High‐grade arrhythmias; e.g., prolonged VT; paroxysmal atrial fibrillation/flutter; high grade AV block

• Low exercise capacity, poor HR recovery, and failure to reach target HR are more important predictors of outcome than ST changes

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Baseline ECG

Stress ECG

A current of injury in lead aVR highly predictive of LMCA stenosis, especially when the ST elevations in aVR exceed those in V1 (Yamaji et al. J Am Coll Cardiol 2001;38:1348‐54).

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Septum Lateral

Anterior

Inferior

Anterior/anteroseptalischemia

Normal

Stress Echocardiography

Diastole

Systole

Normal Stress Echo

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Stress Echocardiography‐ Exercise

Advantages• Sensitivity and specificity

comparable to exercise MPI

• No radiation

• Lower cost than MPI

• Assesses chamber size, wall thickness, valvular function

Disadvantages• Subjective interpretation

• More difficult when resting wall motion abnormalities exist

• Poor image quality in a significant number of patients

• Prognostic value uncertain due to limited number of studies

Dobutamine Echocardiography

Advantages• Useful in patients unable to

exercise

• No radiation

• Myocardial viability

• Assesses ventricular function, chamber size, wall thickness, and valvularfunction

• Patients with asthma or COPD

Disadvantages

• Cannot assess functional capacity

• ECG abnormalities less likely to occur

• Requires extensive experience by reader

• Labor intensive

• Ventricular arrhythmias

• Subjective interpretation

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Exercise Myocardial Perfusion

Advantages• Well‐validated to detect

severe coronary disease and to assess prognosis

• Results are reproducible

• Can assess left ventricular size

• More accurate determination of extent of coronary disease and prognosis

• Myocardial viability

Disadvantages• Radiation exposure

• Cost

• Requires longer time commitment

• Specificity depends upon quality control of laboratory and specialty trained readers

• Artifacts

• Additional equipment and personnel needed

Pharmacologic MPS

Advantages

• Accurately assesses coronary artery disease in patients unable to exercise

• Preoperative risk assessment of patients with claudication, musculoskeletal issues

• Relatively safe in selected patients, side effects are rapidly reversed

Disadvantages

• Cannot assess functional capacity

• ECG abnormalities less likely

• Contraindicated in hypotension, sick sinus syndrome, heart block, bronchospastic airway disease, or oral dipyridamole therapy

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Cath: 60% proximal LAD, 90% proximal OM2, occluded RCA with collaterals

CABG: LIMA to LAD, SVG to RCA and OM1

REST

STRESS

REST

STRESS

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Estimated Effective Radiation Doses

Procedure Estimated Effective Dose (mSv)

Chest X‐ray 0.1

SPECT

Technetium‐99m tetrofosmin, rest—stress 8.6

Technetium‐99m sestamibi, rest—stress 10.7

Thallium‐201, stress—redistribution 16.9

Dual isotope thallium‐201 technetium‐99m sestamibi 23.7

CT coronary angiography

Standard 15

Newest 3

Diagnostic catheterization 7

Cost of Stress Testing: UWMCExercise Treadmill Test:

Professional Fee: $111.30

UWMC Facility Charge: $642.00

Total Charges: $753.30

Treadmill Echocardiogram:




Regadenoson Myocardial Perfusion Study:




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Survival with Revascularization: Basics

• PCI has proven benefit in survival with ACS, post‐cardiac arrest with ischemia‐induced VT/VF

• Other than left main disease in a pt without prior CABG, there is no specific lesion for which PCI has any significant benefit in mortality (often Class IIb or Class III indication)

• CABG offers a survival benefit in most cases of severe CAD (1‐3 vessel disease with/without proximal LAD involvement, often Class I, Class IIa)

• Single vessel disease without proximal LAD diseasenosurvival benefit with CABG or PCI

• SYMPTOMS despite medical therapy, esp in prior CABG pt, is a good indication for PCI

Chest Pain in Women

• Unique presentation compared to men

– Later presentation (10 years older)

– More likely to present with chest pain than myocardial infarction

– Less typical angina

– Intense pain

– Different descriptors (burning or sharp)

– Symptoms unrelated to pain

– Frequent pain in neck and throat

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Women• Diagnostic accuracy is less: greater release of catecholamines during exercisecoronaryvasoconstrictionhigher incidence of abnormalities

• False positive results more common during menses or pre‐ovulation, and post‐menopausal on estrogen

• Initial evaluation of women with suspected CAD, normal ECG, and ability to exercise should be ETT

• In symptomatic women with intermediate likelihood of CAD, imaging procedures should be considered as initial test when resting ECG is abnormal, or exercise capacity is questionable

Diabetic Patients

• May not have classic symptoms

• May have silent ischemia or infarction– DIAD Trial

• 22% with silent ischemia in asymptomatic patients

• 5% with large defects

– Retrospective studies suggest higher rates of silent ischemia (up to 60%) with high risk findings in 20%

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Case #1

• 67 year old man s/p inferior STEMI and 4 vessel CABG in 2008 presents with exertionalchest pressure x 2 weeks that occurs while walking his dog

• ECG demonstrates sinus rhythm with inferior Q waves

• Prior resting echo confirms prior MI, thinning and akinesis of the inferoposterior wall

What test would you order?

A. None‐‐reassurance and look for other causes of chest pain

B. Exercise treadmill test (ETT)

C. Treadmill echocardiography (TME)

D. Dobutamine stress echocardiography (DSE)

E. Exercise myocardial perfusion study (MPS)

F. Nuclear myocardial perfusion study (MPS)

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Assessment of Case #1

• Typical angina

• High pretest probability

• Recommend stress testing for risk stratification and to localize area of ischemia

• Exercise preferred to pharmacologic testing

• Myocardial perfusion imaging may be more interpretable than echocardiography (baseline wall motion abnormalities)

Case #2

• 52 year old woman with history of hypertension, tobacco use disorder, and severe COPD who presents with sharp chest pain with exertion associated with palpitations, relieved by rest

• On exam, patient has diffuse expiratory wheezing

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Baseline ECG








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• Atypical chest pain

• Intermediate pre‐test probability (at least 31%, not including risk factors)

• Recommend stress testing for further risk stratification

• Stress testing with imaging due to baseline ECG abnormalities (WPW pattern, pre‐excitation)

• Dobutamine echocardiography (active wheezing on exam); adenosine is contraindicated

Case #3

• 30 year old woman with no risk factors who presents with recurrent sharp chest pain, not associated with exertion, lasting a few seconds

• Normal exam, ECG

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Analysis of Case #3

• Non‐cardiac chest pain

• Very low retest probability (2%)

• Reassurance

• Identify non‐cardiac cause

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Case #4

• 64 year old man with history of chronic atrial fibrillation, hypertension, and dyslipidemia who presents with recent substernal chest pressure lasting 5 minutes, occurs at rest, sometimes associated with exertion

Baseline ECG

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A. None‐ reassurance and look for other causes of chest pain

B. Exercise treadmill test (ETT)C. Treadmill echocardiography (TME)D. Dobutamine stress echocardiography

(DSE)E. Exercise myocardial perfusion study

(MPS)F. Nuclear myocardial perfusion study

(MPS)


• Atypical chest pain

• Intermediate pre‐test probability (at least 72%, not including risk factors)

• Recommend stress testing for further risk stratification

• Stress testing with imaging due to >1 mm ST segment depressions at baseline

• Stress echocardiography (no radiation)

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Case #5

• 45 year old man with history of hypertension presents with sharp chest pain

• Symptoms do not occur specifically with exertion

• ECG and exam normal








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Analysis of Case #5

• Non‐cardiac chest pain

• Intermediate pretest probability (at least 13%, not including hypertension)

• Recommend further risk stratification with stress testing

• Normal ECG: exercise treadmill test

Take Home Points

• Pre‐test probability should be used to decide whether stress testing is indicated or not

• Exercise treadmill test is the appropriate initial screening test for most patients

• Stress testing modality should be chosen based on co‐morbidities, ability to ambulate, purpose of evaluation

• Full review of primary data, discussion with specialists, will yield optimal management

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