Modern Management in

Primary Care (AF2)

Dr Yassir Javaid

Primary Care Cardiovascular Lead

East Midlands Strategic Clinical Network

Dr Ravi Assomull

Consultant Cardiologist

London North West Healthcare NHS Trust

Warfarin has a narrow therapeutic window

Based on Hylek EM, Singer DE. Risk factors for intracranial hemorrhage in outpatients taking warfarin. Ann Intern Med. 1994;120:897-902

Poor INR control increases morbidity

and mortality in clinical trials

Poor controlTTR<60%n=1,190

Moderate controlTTR 60–75%

n=1,207

Good controlTTR>75%n=1,190

# Risk Factors (%)12>3

28.530.341.2

30.129.640.3

29.135.735.2

Mortality (%/year) 4.20 1.84 1.69

Stroke/systemic embolism (%/year) 2.10 1.34 1.07

Major bleeding* (%/year) 3.85 1.96 1.58

3,587 patients randomised to warfarin (target INR 2–3) in SPORTIF III & V

Mean follow-up (± SD) of 16.6 ± 6.3 months

*Excluding haemorrhagic stroke

White et al. Arch Int Med 2007;167:239–45.

Poor INR control increases the risk of stroke

in real-world practice

.

100

90

80

0 20 40 60 80 100

95

85

75

I I I I I I

< 30

31–40

41–50

51–60

61–70

> 70

%TTR

No warfarin

Months

% o

f p

atie

nts

wit

ho

ut

stro

ke

Adapted from Gallagher et al. Thromb Haemost 2011;106:968–77.

Stroke survival in 37,907 AF patients – UK General Practice Research Database

(27,458 warfarin users and 10,449 not treated with an antithrombotic)

NICE Guideline for AF (June 2014)

• Review TTR at each visit (exclude 1st 6 weeks and must be over a period of ≥ 6/12):– Reassess if over the past 6 months

• x2 INRs > 5 or x1 INR > 8 or x2 INRs < 1.5

• TTR < 65%

• Try to correct and take into account reasons for poor control:– Cognitive function

– Adherence

– Illness

– Interacting drug Rx

– Lifestyle inc diet and EtOH

• If cannot be improved consider other strategies

Could we have predicted the poor control?

• COPD

• Variable EtOH intake

• Dosette box for other meds

• Other drugs

• Compliance of monitoring / patient preference

• Diet???

Switching between Anticoagulants

• Switching from warfarin to a NOAC:• INR < 2.0: start NOAC immediately

• INR 2.0-2.5: start NOAC the next day

• INR > 2.5: Need to estimate from INR value when INR likely to drop below threshold (t1/2 warfarin 36-42h)

• Switching from NOAC to warfarin:• Initiate warfarin with NOAC concomitantly until INR ≥ 2

• Re-test INR 24hrs after NOAC discontinuation

• Missed doses:– pt should take forgotten dose up till 6h (if bd NOAC) or 12h (if od

NOAC) after scheduled intake

– otherwise skip dose and take next dose as scheduled

Dabigatran antidote readily available:

Development process

• Monoclonal mouse antibody developed with high dabigatran binding affinity

• Monoclonal antibody was then humanized and directly expressed as a Fab fragment in mammalian cells (hamster)

• van Ryn J. Presented at the AHA Congress, Los Angeles, USA. 5 November 2012. Presentation 9928

Humanized Fab

Chimeric Fab

Human

Mouse

Mouse antibody

Fab region

Fc region

Job Code: UK/DBG-161104 Date of Prep: May 2016

Anticoagulation prior to planned proceduresNOAC should be stopped 1-2 days prior to procedure depending on whether low

or high risk surgery

Interventions not necessarily requiring discontinuation of anticoagulation

Interventions with minor bleeding risk (i.e. infrequent or with low clinical impact)

NOAC should be stopped 24 hrs prior to procedure

Endoscopy with biopsyProstate or bladder biopsyElectrophysiological study or catheter ablation for right-sided supraventricular tachycardiaNon-coronary angiographyPacemaker or ICD implantation (unless complex anatomical setting,e.g. congenital heart disease)

Dental interventions:- Extraction of one to three teeth- Periodontal surgery- Incision of abscess- Implant positioning

Cataract or glaucoma interventionEndoscopy without surgerySuperficial surgery (e.g. abscess incision, small dermatologic excisions, etc.)

Anticoagulation prior to planned proceduresNOAC should be stopped 1-2 days prior to procedure depending on whether low

or high risk surgery

Interventions with major bleeding risk (i.e. frequent and/or with high impact)

NOAC should be stopped 48 hrs prior to procedure

Interventions with major bleeding risk AND increased thrombo-embolic risk

Catheter ablation of simple left-sided supraventricular tachycardia (e.g. WPW)Spinal or epidural anaesthesia; lumbar punctureThoracic surgeryAbdominal surgeryMajor orthopaedic surgeryLiver biopsyTransurethral prostate resectionKidney biopsyExtracorporeal shockwave lithotripsy (ESWL)

Complex left-sided ablation (PVI- AF ablation; some VT ablations)

Patients with AF and CAD may need combination Rx:Oral Anticoagulant (OAC) + Antiplatelet(s) (AP)

• ESC 2014 guidance:

– For patients with AF and stable CAD (with no ACS or PCI within 1 year):

• Anticoagulant only will suffice

– For patients with AF who have had a PCI or ACS within a year:

• 1st 4 weeks to 6 months:

– Anticoagulation plus dual antiplatelet Rx (exact period depends on whether stent is used, type of stent and bleeding risk)

• Until 12 months:

– Anticoagulation plus single antiplatelet Rx (aspirin or clopidogrel)

– Dual or triple therapy ↑↑ bleeding risk

– (Discuss with cardiologist before stopping any AP < 1 year post PCI/ACS)

Minimal data available for NOACs with newer APs (ie ticagrelor & prasugrel)

Antiplatelet therapy in AF patients post ACS or PCI

Lip et Al Europace doi:10.1093/europace/euv309

- circa 2000 -2008 ↑risk stent thrombosis)

What if bleeding risk too high for A/C?- Left Atrial Appendage Occlusion

Safe Prescribing of NOACs

• Counselling the importance of strict adherence to therapy is the most crucial aspect of NOAC Rx (reinforce at every FU)

• Routine monitoring:• Hb and liver fct (annually)

• Renal function

– Annually for CKD stage I–II (CrCl ≥60 ml/min)

– 6 monthly for CKD stage III (CrCl 30–60 ml/min)

– 3 monthly for CKD stage IV (CrCl ≤30 ml/min)

• Regular (3 monthly) follow up:– Counselling

– Side effects

– Medication review (interactions)

Safe Prescribing of NOACs (2)

• NOAC therapeutic 2 hrs after first intake and peak effect at 3 hrs

• No readily available quantitative assay for NOACs:– aPTT may provide a qualitative assessment for dabigatran

– PT may provide a qualitative assessment for rivaroxaban (and likely other Factor Xa inhibitors)

– INR completely unreliable for the evaluation of NOAC activity

• Dabigatran predominantly renally excreted (80%) and apixaban / rivaroxaban predominantly hepatically eliminated

Safe Prescribing of NOACs (3)

• Main significant drug interactions:

– Verapamil (use lower dose dabigatran)

– Amiodarone

– Dronedarone

– “Azole” antifungals

– HIV protease inhibitors

– Rifampicin, St John’s wort and phenytoin

– PPIs have no clinically significant effect on NOAC bioavailbability

• Rivaroxaban should be taken with food for maximum absorption

Switching between Anticoagulants

• Switching from warfarin to a NOAC:• INR < 2.0: start NOAC immediately

• INR 2.0-2.5: start NOAC the next day

• INR > 2.5: Need to estimate from INR value when INR likely to drop below threshold (t1/2 warfarin 36-42h)

• Switching from NOAC to warfarin:• Initiate warfarin with NOAC concomitantly until INR ≥ 2

• Re-test INR 24hrs after NOAC discontinuation

• Missed doses:– pt should take forgotten dose up till 6h (if bd NOAC) or 12h (if od

NOAC) after scheduled intake

– otherwise skip dose and take next dose as scheduled

A guide in how to get it right every time in

Primary Care

Dr Ravi Assomull

Consultant Cardiologist

London North West Healthcare NHS Trust

Dr Yassir Javaid

Primary Care Cardiovascular Lead

East Midlands Strategic Clinical Network

‘Basics’ of 12 lead - electrophysiology

LV

RV

aVF IIIII

I

aVL aVR

The limb leads (vertical plane):

‘Basics’ of 12 lead - electrophysiology

Inferior

Lateral(high)

The Interventional Cardiologist’s

Approach(Leads I and II)

Indeterminate

Axis

V1

V1

V2

V2

V3

V3

V4

V4

V5 V5V6

V6RA

LA

LV

RV

‘Basics’ of 12 lead - electrophysiology

The precordial leads (horizontal plane):

All 12 ‘views’ of the heart

AVR AVL

AVF

I

IIIII

V1

V2

V3

V4 V5

V6

Anterior V1, V2, V3, V4

Lateral I, AVL, V5, V6

Inferior II, III, AVF

ECG Territories (relating mainly to LV)

Lateral

Lateral

Anterior / Septal

LateralInferior

LCx or diagnonal

branch of LAD

LAD

RCA or LCx

LCx or diagnonal

branch of LAD

LCx or diagnonal

branch of LAD

ECG Territories (relating mainly to LV)

Cardiac Conduction System

0.12 -0.2 secs

(3 – 5 small squares)

< 0.12 secs

(3 small squares)

How to interpret a rhythm

• What is the ventricular (QRS) rate?• If regular = 300 / no of large squares between QRS complexes

• If irregular = no of QRS complexes in 30 large squares (6 secs) x 10

• Is the QRS rhythm regular or irregular?

• Is the QRS duration normal or prolonged (ie > 3 small squares)

• Is atrial activity present?

• How is atrial activity related to ventricular activity?

• What is the cardiac axis?

LBBB

Depolarisation spreading from right to left ventricle through non-specialised conductive

tissue (hence slower and widening of QRS)

Pathological Q waves

Pathologic Q waves are a sign of previous MI:

• result of absence of electrical activity

• MI = an electrical 'hole' as scar tissue is electrically dead, resulting in pathologic Q waves

• Generally take several hours to days to develop

• Once developed they rarely go away unless MI is reperfused early (e.g. post PCI).

• Stunned myocardial tissue can recover and pathologic Q waves disappear.

• In all other situations they usually persist indefinitely

• Latest definition as accepted by the ESC and ACC:

• Any Q-wave in leads V2–V3 ≥ 20ms

• Q-wave ≥ 30ms in any two leads of a contiguous lead grouping:• I, aVL,V6; • V4–V6; • II, III, and aVF

• Major Q waves: Q ≥ 50ms or Q ≥ 40ms AND R/Q < 4 (Novacode System)

Notes:

• Absence of pathologic Q waves does not exclude a myocardial infarction!

• Lead III often shows Q waves, which are not pathologic as long as Q waves are absent in leads II and aVF (the contiguous leads)

• Q waves acceptable in aVR and V1

Pathological Q waves (2)

Normal vs Pathological Q waves

Normal

• Duration < 0.04s (ie 1mm)

• Depth < 2mm in I and II < 1mm in other leads

• Deeper isolated Q wave in III is often normal- often associated with inverted T- both disappear with deep inspiration

Pathological

• If exceed above criteria

• Particularly if in contiguous leads

• Usually > 25% height of R wave in the same complex

General approach to tachycardias

QRS width

Irregular

AF

Regular

SVT

or

A Flutter(if HR 150)

Narrow

Irregular

TdP

or

AF + BBB

or

Pre-excited AF

Regular

VT

Broad

SR with

BBB

No

P waves P waves

Sinus

tachy

No

P waves P waves

Accessory Pathway

Accessory Pathway: Pre-excitation

WPW (AVRT)

Sino-atrial disorder

• Progressive failure of SA node

• Common finding in the elderly

• Constant PR interval (preserved A-V conduction)

• Sinus pauses

The anatomy of heart block – possible sites

Sino-atrial

disorder

HCM

• Autosomal dominant• 50-60% have identified gene mutation

The T wave

• No specified normal range• Normally upright (except V1 and aVR)• Symmetrical• Normally not more than half the size of preceding QRS

complex

Normal

The T wave

• Hyperkalaemia• Hyperacute changes MI

Tall

The T wave

Important causes are:

• Physiological• Myocardial ischaemia• Hypothyroidism• Pericarditis

Flat

The T wave

Important causes are:

• Myocardial ischaemia• Non-ST elevation MI• Pericarditis• Hypokalaemia• LVH• Hyperventilation• Physiological• Complete Heart Block

Inversion

The anatomy of heart block – possible sites

1st Degree HB

2nd Degree HB T1 “Wenkebach”

Sino-atrial disorder

2nd Degree T2

3rd Degree Complete HB

Summary Abnormal Results : ECG

Abnormal Urgent Abnormality

• Rhythm other than sinus (eg AF)• PR interval >220ms• Heart rate <50 bpm (patient well)• T wave inversion (other than V1, AVR & 3)• Left axis deviation• Voltage criteria for LVH• ST segment depression• QTc > 460msecs• Sinus pauses > 3 secs• Ectopy (other than isolated SVE)• Evidence of pre-excitation (delta wave)• LBBB• RBBB if symptoms or LAD

• ST depression (>2mm) or elevation in ≥ 2 concordant leads

• ST or T wave changes in association with chest pain

• Broad complex tachycardia (≥ 3 beats) • Narrow complex tachycardia > 150 bpm or

with symptoms• Complete heart block • Second degree heart block with symptoms

(syncope or Presyncope) • QTc > 500msecs• Ventricular standstill > 2 secs

Summary Abnormal Results: 24 Hr ECG

Abnormal Urgent Abnormality

• Arrythmias other than asymptomatic isolated ectopy

• > 500 ventricular ectopics• Any degree of heart block• ST segment changes• Daytime pauses > 3secs• Nightime pauses > 4 secs• Prolonged QTc (> 460msecs)

• Broad complex tachycardia (sustained or <30 seconds with symptoms)

• Sustained narrow complex tachycardia > 150bpm (or with symptoms)

• Complete heart block • Second degree heart block with symptoms• Any symptomatic bradycardia (syncope or

presyncope)