เอกราช อริยะชัยพาณิชย์

Aekarach.a@chula.ac.th

Internal Medicine Board Review 2019

16.11.2019
 Disclosure
There is event is organized by Siam Pharmaceutical

• Speaker, CME service:

AstraZeneca, Boehringer Ingelheim, Merck, Novartis, Thai-Otsuka, Roche Diagnostics, Servier
• Consultant, non-CME service:
Novartis
 Agenda

1. Forget that HF is deadly

2. Do not just remed
3. Too little too late in AHF
4. Nothing to do in HFpEF
5. One big team
 Forget that HF is deadly

Landmark trial in CV disease Death/yr • High symptom burden

• Family, care giver
Stage C HFrEF (OPD)
(PARADIG-HF NEJM 2014)
8.2% • Most common admission
ACS
diagnosis in Medicine Ward
5.2%
(PLATO NEJM 2009) • High readmission rate
Chronic AF
2.0%
• More patient with aging society
(ARISTOTLE NEJM 2011)
• Highest health care cost
Stable CAD
0.8%
(FAME II NEJM 2012)

Stable CAD + LV dysfunction

6.5%
( BEAUTIFUL Lancet 2008)

Severe AS (suitable for Sx)

25%
(PARTNER A NEJM 2011)
Heart failure need your attention!

Patients survive to discharge at King Chulalongkorn

Memorial Hospital (both HFrEF and HFpEF)
 Agenda

1. Forget that HF is deadly

2. Do not just remed
3. Too little too late in AHF
4. Nothing to do in HFpEF
5. One big team
AIM FOR THE TARGET !
 Stepwise approach in
chronic HF
ESC 2016

ACC/AHA 2017
2109 Thai HF guideline
Thai HF guideline 2019
• 8 articles in English published in JMAT
• Thai version and PowerPoint version is coming
 Tips and tricks of medication titration for HFrEF
First thing first: Control volume with loop diuretic
• Never underdiurese
• Wt log - Do not underestimate patient selfcare
STEP 1. ACEI + BB
ACEI BB
Try ACEI before ARB Use HF’s BB (B, C, M, N)
ARB is cough If asthma/COPD use N >> B >> M
CKD is not a contraindication for ACEI/ARB If hypotension use B, N
Never ACEI+ARB+MRA
STEP 2. MRA, ARNI, Ivabradine, digoxin
Spironolactone if Cr <2 or 2.5, K <5
Sac/Val if can tolterate ACEI/ARB and Cr <2 or 2.5, K <5, SBP >100
Ivabradine if HR >70 bpm and in sinus
Digoxin highly symptomatic, recent/ repeat HF admission ACEI BB MRA
STEP 3. After OMT get an echo to eval for ICD/CRT
ARB
 Test yourself
A 62 yo man with new diagnose HF with
LVEF of 20% from outside hospital
- H/o HTN, AF
- Recent DC 1 wk ago. Now NYHA II
- No CAD on CAG

Med
Furosemide (40) 1x2
KCL 30 ml bid
Carvedilol (6.25) 0.5x2
Enalapril (5) 1x2
warfarin
ASA 81 mg
simvastatin (40) 1x1
amiodarone (200) 1x2
omeprazole

Cr 1.02, K 3.3
INR 2.04
 Case

A 62 yo man with HFrEF, HTN, AF

Med
Furosemide (40) 1x2 ? ↓ furosemide Cr, K
KCL 30 ml bid ?Adding spironolactone
Carvedilol (6.25) 0.5x2 ↑ carvedilol slowly
at 1 week
Enalapril (5) 1x2 ↑ACEI … ?Let replace with ARNI
warfarin NOAC is preferred
ASA 81 mg Stop ASA if no other indications
Follow up
simvastatin (40) 1x1 Stop statin if no other indications at 2-4 weeks
amiodarone (200) 1x2 Why? AF? VT? … Stop it … Ablate it? (CASTLE-AF NEJM 2018)
omeprazole ? indication

Cr 1.02, K 3.3
INR 2.04
 More about ARNI
COR LOE ESC 2016
Sacubitril/valsartan is recommended as a replacement for
an ACE-I to further reduce the risk of HF hospitalization and
I B death in ambulatory patients with HFrEF who remain
symptomatic despite optimal treatment with an ACE-I, a
beta-blocker and an MRA

PARADIGM-HF STUDY
NEJM 2014;371:993
• N= 8442 - Chronic HF
• LVEF < 35-40%, NYHA II-IV, Stable on ACEI/ARB
(equivalent to enalapril ≥ 10 mg/day)

NEJM 2014;371:993
.
ARNI initiation
 Agenda

1. Forget that HF is deadly

2. Do not just remed
3. Too little too late in AHF
4. Nothing to do in HFpEF
5. One big team
Treatment of acute HF

• Diuretics
• Vasodilator
• Inotrope

Bailout
• Ultrafiltration
• Vasopressor
• Mechanical circulatory support
• IABP, ECMO, VAD

2016 ESC HF Guideline

 “time-to-treatment” approach

Then look for life threatening triggers

2016 ESC HF guideline

 Hemodynamic profile in Acute HF

2016 ESC
HF guideline
 Diuretic use in acute HF

• Sooner is better
• First dose: 20-40 mg or = home oral dose
• Evaluate q 2-4 hours
• Urine > 150 ml/hr, Una >50
• Max dose of Lasix is not 1 g/day … Think
• 240mg/hr in 6 hours
• 160 mg bolus then 40 mg /hr for 2 hrs
• Early combination
• HCTZ, MRA, Tolvaptan
• Always optimize renal perfusion in cardiorenal
• Bailout ultrafiltration
 Thiazide diuretic MRA Vasopressin antagonist
Na/Cl cotransporter in Na/K ATPase in Aquaporin channel in collecting
distal convoluted tubule collecting tubule tubule

HCTZ 25-100 mg Spironolactone 25-100 mg Tolvaptan 7.5 - 60 mg

Chlorthalidone 50-200 mg
Prefer if
Chronic loop users Hypo K Hypo Na
GFR <30
Caution in
Hypo K AKI Alteration of metal status
Hypo Na Hyper K Na > 135
J Am Coll Cardiol 2010;56:1527–34 ATHENA-HF TACTICS-HF
JAMA Cardiol 2017;2(9):950. J Am Coll Cardiol 2017;69:1399.
 Vasodilator is underuse

1. Use vasodilator in most patient,

except SBP < 90 or MAP < 65
• Improve forward flow
2. Identify Cold patient
• Δ mental status
• Not that bad Cr but hard to diuresis
• Pre shock e.g., AST/ALT 200-300, INR 1.4
3. Inodilator before vasopressor
• dobutamine, milrinone, levosimendan
 In patients who survive AHF admission,
The most important part is to transitioning to home
• Make sure optimal response to oral
diuretics
• do not under-diurese
• Document dry weight
• Identify triggers/precipitating factors
• Do echocardiogram especially de
novo HF
• Justify benefit of coronary angiogram
• Enroll in HF clinic
• Provide HF self-care education
• Identify key person and patient’s
supporting system
• Up titrate BB/RAAS blockage if HFrEF
 Agenda

1. Forget that HF is deadly

2. Do not just remed
3. Too little too late in AHF
4. Nothing to do in HFpEF
5. One big team
 Summary of definition and diagnosis

▪ LAVI > 34 ml/m2; LVM ≥ 95 – 115 g/m2; E/e’ > 13; e’ <9 cm/sec
▪ In case of uncertainty,
▪ RHC to invasively measure elevated LV filling pressure (LVEDP,
PCWP, PA) at rest or during stress test may be needed.

ESC 2016 HF guideline

HFpEF is as deadly as HFrEF

N Engl J Med 2006;355:251-9.

 TOPCAT

CHARM
PARAGON-HF – ARNI in HFpEF
 What is your HFpEF
“Non-cardiac dyspnea”
Lungs, obesity, deconditioned, depression
BNP/NT-proBNP may help HFpEF and phenotypic spectrum

HTN
COPD Diastolic
dysfunction

Specific HFpEF Frailty

Aging
CAD
HCM Anemia

Constrictive pericarditis HFpEF

AF
Infiltrative CM -Amyloid Vascular
PH dysfunction
Valvular heart – AS, MS, MR Obesity
CKD
Pure RV failure – RV infarct, ARVD OSA DM
High output HF PAH – gr1 MI

Ariyachaipanich A
 Agenda

1. Forget that HF is deadly

2. Do not just remed
3. Too little too late in AHF
4. Nothing to do in HFpEF
5. One big team
We are a part of one big team
Transplant, VAD
HF
specialist

Set up HF clinic, eval for CRT/ICD

eval for prognosis Cardiologist

Dosing optimization
Stabilize acute HF Internal Medicine

Recognition, Initial Rx General practictioner

Awareness/ controlling risk factor Health care provider

 Management of
Stage D HF

HTx

LVAD

Home
inotrope

Yancy CW. ACC/AHA HF guideline. Circ 2013;128:e240-e327 Palliative

care
Time to refer
Thank you for your attentions!
Supplement slides
 PARADIGM-HF (NEJM 2014)

ARNI proven superiority

over ACEI

• N= 8442 NNT =21, f/u 27 m

• LVEF < 35-40%, NYHA II-IV, Stable
on ACEI/ARB (equivalent to
enalapril ≥ 10 mg/day)
• Sac/Val vs ACEI
• F/U 27 mo
• Sig. improved
• Death 13.3% vs 16.5%
• HF hosp 12.8% vs 15.6%

N Engl J Med 2014;371:993.

Symptoms ± signs then echo for diagnosis of HF

Think probability “how likely this patient having HF”

• Unlikely → BNP/NT-proBNP, CXR to r/o HF

• Likely → Echo

2016 ESC HF Guideline

 BNP, NT-proBNP can help with diagnosis of HF

2019 HFCT HF guideline

2016 ESC HF Guideline: Novel contribution
1. HFrEF, HFmrEF (40-49%), HFpEF
2. BNP as a diagnosis criteria of mrEF, pEF
3. Likelihood of HF
4. ARNI in HFrEF (I, B)
5. Ivabradine (IIa, B)
6. CRT is contraindicated in QRS <130ms
7. Comorbidities management
8. Time to treatment approach and CHAMP
9. Acute HF: warm-wet-cold-dry

2016 ESC HF guideline

Likelihood of HF and diagnosis during an outpatient
• HF is very common and may not be easily,
but can be diagnosed during outpatient
visit.

• In low likelihood patient, “easy” to rule out

by BNP/NT-proBNP

• Most patients in Thailand was diagnosed by

“first congestion admission”

• Think …
• Post chemo
• Familial cardiomyopathy
• Elderly with fatigue
• Echo is not available / screen for echo
2016 ESC HF guideline
 Diuretic resistance is associated with poor outcomes

COR LOE ESC 2016

In patients with new-onset AHF or those
with chronic, decompensated HF not
receiving oral diuretics the initial
I B recommended dose should be 20–40 mg i.v.
furosemide (or equivalent); for those on
chronic diuretic therapy, initial i.v. dose
should be at least equivalent to oral dose

European Heart Journal (2014) 35, 1284–1293

 SHIFT (Lancet 2010)
• RCT, double-blind, placebo-controlled
• N= 6558 pt with HFrEF, NYHA II-IV
NNT =24, f/u 23 m
• Sinus, HR ≥ 70 bpm, HF hosp within 12 mo.
• Ivabradine 5-7.5 mg bid vs placebo
• 79% ACEI, 14% ARB, 90% BB, 60% MRA, 84% diuretic, 22%
digoxin
• Mean F/U 23 months

• Ivabradine is associated with  composite of CV death or

HF hospital admission
• 24 vs. 29%, HR 0.82; p<0.0001

Lancet 2010;376: 875–85.

Suggested diuretic regimen