Valvular Heart Disease

Dr Phil Boreham,

Consultant Cardiologist

Southmead Hospital

Valvular Heart Disease

Valvular Heart Disease

Valvular Heart Disease

Historically VHD mostly caused by rheumatic fever - streptococcal pharyngitis treated by penicillin

Rare in the 1st world, but still common in the 3rd world

Now VHD is due to degenerative changes of valve tissue

From 2030, in most of Europe, all adult age groups under 65yrs will be in decline

Between 2005 - 2050 pts>80yrs will rise from 19Million to 51Million (Europe)

VHD rate rises from 0.5% of pts 18-44 yrs to 15% of pts> 75yrs

VHD affects the elderly

Valvular Heart Disease

UK approx 1 million pop >65 yrs have VHD,

UK pop aged >75yrs in 2025 will be 50%

greater than it was in 2012

VHD affects 15% of pts> 75yrs

Aortic stenosis + Mitral Regurgitation make up most

Tricuspid Regurgitation is very very common and

usually not clinically relevant. When found with

Pulmonary Hypertension – it is the Pulm HT that is

the cause of breathlessness.

Valvular Heart Disease

VHD is 2 valves

1, Aortic Stenosis 40% - degenerative (~half are bicuspid)

2, Mitral Regurgitation 45% - degenerative

3, Aortic Regurgitation 10% - degenerative (~half are bicuspid)

4, Mitral Stenosis 2% - 2° to rheumatic fever

5, the rest 3% - mostly Tricuspid Regurg

Gender Males♂ = Females♀

Valvular Heart Disease

Aortic Sclerosis AScl (not Stenosis)

Thickening of AV +/- Ca2+

present in 25% of >65yrs pop

(1 in 6 will > severe AS in 5yrs, more later)

[usually a problem of >70yrs]

Aortic Stenosis – 40% of VHD

Aortic Stenosis AS

Echo shows Ca2+ in AV in 40% >65yrs, and 75% >85yrs

Clinically significant AS occurs in 2-3% in >70yrs pop

Commonest assoc is Bicuspid AV (~1/2 of cases)

Bicuspid in 1-2% of gen pop, male ♂2:1♀ female

⅓ Bicuspids will develop Ca2+ and significant stenosis before age of 70yrs

Valves –

Valvular Heart Disease

Aortic valve surveillance

Symptomatic patients ( Angina, SoBonEx, Presyncope) refer to Cardiology

Asymptomatic patients Echo baseline and re-Echo at 1 year to assess progress

Mild - Peak gradient < 35 mm Hg, good/normal LV function re-Echo 3yrly intervals

Mod - Peak gradient 35-50 mm Hg, good/normal LV re-Echo 2yrly intervals

Mod/Severe - Peak gradient >50 mm Hg refer to Cardiology

For Bicuspid Aortic valves

Peak gradient <35 mm Hg re-Echo 2yrly intervals

Peak gradient >35 mm Hg refer to Cardiology

Aortic stenosis & impaired LV function refer to Cardiology

Aortic Regurgitation AR – 10% VHD

Causes:-

1, atherosclerosis / ageing of Aorta > dilatation

2, Bicuspid AV

1&2 = 90%

Few are:- Post Infective Endocarditis,

rheumatic fever, Inflamatory Aortitis – RA,

Ank Spod, Giant Call Arteritis, Syphilis

Mitral Regurg MR – 40% VHD

1, Myxomatous degeneration (baggy leaflets & stretched chordae)=(MVP) Females♀ > Males♂

2, Ischaemic Heart disease, LV uncoordinated after MI Males♂>Females♀

3, Dilated Cardiomyopathy incl 2° to ischaemic Hrt Dis

Males♂ = Females♀

Patients age >75 years having cardiac surgery for Mitral valve have an operative mortality 5 - 10%

5yr survival of 55%

Mitral valve surveillance for MR

Echo and re-Echo 1 year later

Pts with > Moderate MR refer to Cardiology if appropriate

Pts >80 yrs no follow up (Surgery rarely performed - poor outcomes)

Mod/Severe MR + symptoms of SoB in < 75yrs will be considered for open heart repair surgery

Severe MR + symptoms in >75yrs may be considered for MitraClippercutaneous procedure – expensive with moderately good outcomes.

How to triage referrals

The Echo report 2 important features:-

1, LV function 2, degree of Valve Disease, 3, Pulm HT, the rest

much less important

If your 1st Echo says:-

mod or severe ...VHD OR mod or severe LV impairment

refer to Cardiology (if in pts best interest)

If 1st Echo says mild/mod or moderate … VHD and

good/normal/mildly impaired LV function

then re-Echo 1 year later.

When do valves go bad?

1, Aortic Stenosis in pts >70 yrs, rarely in younger pts. Pts into

early 80s do well with AValve surgery and (with a higher risk)

with Balloon Aortic valve stent TAVI -(Partner trials)

2, Mitral Regurg in pts aged 50 – 75yrs, - MV repair surgery do well

BUT, Pts >75yrs do relatively well on oral meds and do relatively

badly with mitral valve surgery

3, any patient can get Bacterial Endocarditis and go off quickly –

over a few weeks – night sweats, fevers, myalgia, SoB,

splinters, conjuntival and retinal haemorrhages, blood in urine

CRP ++, mild anaemia

Antibiotic prophylaxis in VHD

NICE guidance at odds with Cardiology

Dental work or any potentially infective procedure – abcess drainage etc

Absolute indications for prophylatic antibiotics

1, valve replacement in situ

2, PMH of endocarditis

3, mod/severe Aortic Stenosis, VSD, congenital heart disease, Mitral stenosis

Treatment of VHD

Regurgitant valves: - AR, MR and TriCuspV R

Rx as chronic heart failure – ACE, low dose

diuretic, Betablocker particularly if in AFib

Stenotic valves:- AS and MS

Rx as hypertension – Betablocker, long acting

ACE (Perindopril) –start low dose. Mild

diuretic – Indapamide or BFZ

Surgery or Catheter delivered devices

End

Heart Failure

Systolic – weak heart

- Left Ventricular Failure = systolic impairment of LV

- BiVentricular Failure = CCF = systolic impairment of LV + RV

- Rt Heart Failure = usually due to Lung disease causing Pulm HT

Diastolic – stiff heart

- Diastolic Dysfunction – impairment of relaxation of LV

- Usually found in elderly, longstanding HT or Aortic valve

stenosis

Risk Factors

Heart Failure

PMH of Cardiac disease eg:-MI, CABG, stents, valve, AFib

Tobacco:- low relevance

HT, DMII, - high relevance

Alcohol excess – relevant

Age:- not useful

- old HTensive pts

- young pts with recent viral myocarditis

Pulmonary disease

PMH of pneumonia/chest

infections,

Tobacco:- high relevance

HT, DMII - low relevance

Alcohol excess – low

relevance

Age:- not useful

PMH of system

disease:-

The usual risk

factors:-

Tobacco

HT & DMII

Alcohol

Age

Investigations in Primary care

ECG

Pulse oximetry

Peak Expiratory Flow meter

Cardiac

ECG – usually

abnormal (a

normal ECG

excludes heart

failure)

In normal range

in CCF, maybe

hypoxic in acute

LVF

PEFR normal

Respiratory

ECG – usually

normal, may have

signs of Right

Heart strain – cor

pulmonale in

severe chronic

resp disease

Usually in low

range of normal

or below after

exertion

PEFR abnormal

Normal ECG

Abnormal ECG – old Inf MI

Abnormal ECG – recent Ant MI

Abnormal ECG - LBBB

Atrial Flutter

Atrial Fibrillation

Effects of Hypertension

ECG:- LVH

Secondary Investigations

If ECG abnormal or previous MI or murmur present, request

– Echocardiogram

community Heart Failure service

direct access

– BNP venous sample in gold top container for NTpro BNP

- CXR usually unhelpful for early COPD or CCF, but will pick up

malignancies and pleural disease

Diagnosis with BNP

Serum natriuretic peptides – – NTpro BNP assay

Normal levels –NTpro BNP

men<70yrs <100 pg/ml,

women<70yrs <150 pg/ml

Over 70yrs <400 pg/ml

Over 75yrs <500 pg/ml

Often see BNP in >75yrs HT, Afib of 500 – 1000

GREY AREA 100 – 500 pg/ml difficult to assess the relevance

Raised levels –NTpro BNP 100-2000 pg/ml refer for routine Echo (age appropriate)

urgent referral if younger <70yrs

Common levels on admission with acute LVF - 40-80,000 pg/ml

Echo – is still the definitive diagnostic tool for Heart Failure–

If Echo is poor quality use Nuclear Medicine or Magnetic Resonance scan

BNP – Brain type Natriuretic Peptide

BNP – a protein secreted by the Atria&Ventricles of the Heart

BNP < 100 pg/ml makes CCF extremely unlikely

BNP > 500 pg/ml has significant implications - refer to secondary care if appropriate

BNP can be up with LVH, Tachycardia, Ischaemia, Cor Pulmonale/COPD, PE, eGFR<60 ml/min, Diabetes, Cirrhosis and sepsis.

BNP can be reduced in Obesity, diuretics, ACE inhibs, ARBs, Beta Blockers and Aldosterone antagonists

Heart Failure

Natriuretic Peptides NP – group of 3

Atrial, Brain, Central Nv Sys, types - A,B,C, NP

These are beneficial in Heart Failure

Increase Na+ and water excretion

Neprilysin is a metalloproteinase that metabolises the NPs and Bradykinin

Neprilyin worsens Heart Failure

Neprilysin Inhibitor (LCZ696 – aka Sacubitril)

Nep Inh(NI) increases A,B,C NP – bradykinin and substance P levels, resulting in

natriuretic, vasodilatory and anti-proliferative effects

NI – lowers endothelin, vasopressin, sympathetic activity and RAASS

NI+ACEinh results in raised bradykinin levels > facial angioedema

NI+ARB blocks Angitensin II receptors(good vasodilatory effect) with not too much

bradykinin

New drug Entresto is a combination of Valsartan(ARB) + Sacubitril

Side effects BP v, K+ ^, cough 10%, dizzyness 10%, renal failure

SoB due to Heart & Lung disease

BNP can help assess patients – with both COPD and LVF to give an indication of which system is predominant

If COPD pt is SoB - BNP levels are low 100 - 1000

If HF pt is SoB - BNP levels are raised 1000 – 20,000 LVF is not adequately treated.

BNP levels can gauge effectiveness of Rx for Heart Failure (high levels reducing with Rx)

Heart Failure prognosis

Heart Failure NICE 108 Aug 2010

Referral

i, initial diagnosis of heart failure

ii, management of severe – NYHA class IV heart failure, or valve HF, or unable to manage at home

iii, Pregnant women or planning pregnancy

iv, Urgent referral for Pts with suspected CCF and previous MI or Viral illness should have Echo within 2 weeks

Refer to Cardiology those patients in whom prognosis is key, younger patients, the elderly managed in the community

Systolic and Diastolic HF

Heart Failure 2 types:- i,Weak Heart or ii,Stiff Heart

i, CCF or HF rEF (heart failure reduced ejection fraction)

Usually due to poor Systolic function of LV(Cardiomyopathy) most

commonly post MI/Ischaemia, HT, Valvular disease and Viral

Myocarditis aka Dilated Cardiomyopathy

ii, DiastolicHF or HF pEF (preserved ejection fraction)

Less common - Systolic function of LV is good BUT poor LV

relaxation in diastole (diastolic dysfunction – usually seen in the elderly

and those with longstanding HT with LVH and Diabetes)

Rx is not the same as CCF drugs except – Spironolactone or BFZ/

Indapamide

Heart Failure meds

Diuretics

- Loop –Furosemide

- Thiazides – BFZ or Indapamide, (Metolazone – handle with care)

- Anti mineralocorticoids – Spironolactone ( women), Eplerenone(men –

MOOBS)

Beta blockers – Bisoprolol, Carvedilol, Nebivolol

ACE – Perindopril, Ramipril

ARBs – Candesartan - only

Entresto use in LVEF of <35% or NYHA II-IV once pt is stabilised on an

ACEinh for 3 weeks, BP>90sys. Benefit seen in <75yrs

Hydralazine + Nitrates - rarely

Beta Blockers

Use the 3 licensed BB usually Bisoprolol, others being Carvedilol and Nebivolol

NICE says offer BB to ALL adult pts with Heart Failure incl those with

i, peripheral arterial disease

ii, Erectile dysfunction

iii, Diabetes mellitus

iv,COPD

v, Interstitial pulmonary disease / fibrosis

Atrial Flutter

Atrial Fibrillation

The Treatment of all TachyArrhythmias

is:-

Beta Blockers - NICE guidance

Which Beta Blockers – BISOPROLOL and NEBIVOLOL

Atrial Fibrillation – Beta blockers and rarely-Catheter Ablation

Atrial Flutter – Beta blockers and occasionally-Catheter Ablation

Atrial Tachycardia – Beta blockers and Catheter Ablation

SVT – Catheter Ablation and Beta Blockers

VT and VF – Beta blockers and Implantable Cardiovertor Defibrillators (ICD) and occasionally Amiodarone

NB Atrial Fibrillation/Flutter think CHADS2VA2Sc and Oral Anti Coagulant

Treatment

Usual Rx for Systolic CCF,

First line:- ACE inhib/ARB(Candesartan), BB, Diuretic, Aldosterone antagonist ( Spironolactone or Eplerenone) (monitor U+Es)

Second line:- CRT pacemaker only if SR+LBBB on ECG and QRS > 150ms.

Third line:- Implantable Cardiovertor Defibrillator, ICD increases lifespan in patients particularly with prev MI, BUT in patients with extremely poor LV function provides no benefit. Also consider appropriateness of ICD in the elderly who are in a poor prognostic group due to age.

Hypertension to Heart Failure

HT can result in Heart Failure via two routes;-

1, HT > Arterial wall damage > Atherosclerosis > Myocardial

Infarction > Poor LV function

2, LVH will develop myocardial fibrosis > poorly contracting or

relaxing LV > Systolic or Diastolic Dysfunction (stiff heart).

Very limited treatment for Dia Dys:-

1, regular exercise

2, Spironolactone/Eplerenone

Monitor Systolic HF pts

Monitoring CCF Pts

i, Assess Functional capacity, exercise distance, general well

being, fluid=oedema=weight, Pts to weigh themselves 3x week

ii, Heart Rhythm look for AFib for dOAC eg Dabigatran

Control resting Heart Rate to < 70 bpm

If using low doseDigoxin (do levels – if nausea or drug naïve pt.)

iii, U+Es

iv, up titrate Rx at short intervals 1-2 weeks visits no later. Once on

stable Rx 6 monthly visits

Rehab and Support

Rehabilitation

Offer a supervised group exercise-based rehab programme eg

approach current Cardiac rehab programmes for post

MI/CABG/Stent patients

Depression

Depression is common in this group

Consider treatment NICE guide 91 ‘Depression in adults with a

chronic physical health problem’

Be aware of pts self medicating eg St John’s wort in pts who may

need Warfarin or a dOAC

Coming to the end of the line

Prognosis:

Prognosis has been very poor in the past pre- ACE&BB ~50% 1yr mortality after 1st CCF

Prognosis now very much better, but life span reduced depending on state of LV and cause of impairment

Approach prognosis carefully, Mod LV impairment has a mod prognosis BUT

Severely impaired LV likely to be <5years

Terminal Phase of CCF <12 months life expectancy

Features Term Phase :- NYHA 4 SoB at rest

Age +++

Albumin <25 g/L

Cardiac cachexia

3x admissions to hosp in last 6 months

Needs help with 3 x ADLs daily activities

Death is often sudden

Help for Terminal Phase:- put Pts on ASTRA end of life care register

Marie Curie and night sitters

Heart Failure and Entresto

Natriuretic Peptides NP – group of 3

Atrial, Brain, Central Nv Sys Nat Peptides

A,B,C, NP

These are beneficial in Heart Failure

Increase Na+ and water excretion

Neprilysin is a metalloproteinase that metabolises the NPs and Bradykinin

Neprilysin worsens Heart Failure

Neprilysin Inhibitor (LCZ696 – aka Sacubitril)

Nep Inh increases A,B,C NP – bradykinin and substance P levels, resulting in natriuretic, vasodilatory

and anti-proliferative effects

NI – lowers endothelin, vasopressin, sympathetic activity and RAASS

NI+ACEinh results in raised bradykinin levels > facial angioedema

NI+ARB blocks Angitensin II receptors(good vasodilatory effect) with not too much bradykinin

New drug Entresto is a combination of Valsartan(ARB) + Sacubitril

Side effects BP v, K+ ^, cough 10%, dizzyness 10%, renal failure

END

Atrial Flutter

Diagnosis with BNP

Serum natriuretic peptides – – NTpro BNP assay

Normal levels –NTpro BNP

men<70yrs <100 pg/ml,

women<70yrs <150 pg/ml

Over 70yrs <400 pg/ml

GREY AREA 100 – 500 pg/ml difficult to assess the relevance

Raised levels –NTpro BNP 100-2000 pg/ml refer for routine Echo (age appropriate)

High levels –NTpro BNP > 2000 pg/ml refer for urgent Echo

Common levels on admission with acute LVF - 40-80,000 pg/ml

Echo – is still the definitive diagnostic tool for Heart Failure–

If Echo is poor quality use Nuclear Medicine or Magnetic Resonance scan or TOE

Beta Blockers

Use the 3 licensed BB usually Bisoprolol, others being Carvedilol and Nebivolol

NICE says offer BB to ALL adult pts with Heart Failure incl those with

i, peripheral arterial disease

ii, Erectile dysfunction

iii, Diabetes mellitus

iv,COPD

v, Interstitial pulmonary disease / fibrosis

Other Rx for HF

In Pts who cannot tolerate ACE inhib or ARBs

particularly AfroCaribbeans

Rx Hydralazine + Nitrates oral combination

Only use Amlodipine (Ca2+ blocker) to treat HT in HF

pts after all else has failed – otherwise Ca2+ blockers

are to be avoided.

Usually no need for Ca2+ blockers, if BP high use

Carvedilol

Heart Failure meds

Diuretics - loop –Furosemide

- Thiazides – BFZ or Indapamide, Metolazone

- Anti mineralocorticoids – Spironolactone ( women), Eplerenone(men – MOOBS)

Beta blockers – Bisoprolol, Carvedilol, Nebivolol

ACE – Perindopril, Ramipril

ARBs – Candesartan

Entresto use in LVEF of <35% or NYHA II-IV once pt is stabilised on an ACEinh for 3 weeks,

BP>90sys

Hydralazine + Nitrates

DIGOXIN

- Digoxin ONLY to be used in AFib* pts

- Various meta-analyses suggest link with increased mortality

(unclear as to cause and effect)

- Only add Digoxin to Betablocker or Amiodarone not to use

alone

- Use smaller doses 62.5 or 125mcg rather than 250 mcg

Check serum levels in ‘new’ Digoxin pts

Serum level >1.2 ng/ml reduce dose or discontinue

*DIG trial shows Digoxin when added to an ACE inhib + diuretic has little/no

effect when pt is in Sinus Rhythm but had slight beneficial effect when pt in

AFib

Examination

Heart Rhythm

Murmurs

Uinilateral or Bilateral resp signs

Heart failure

AFib common & can

cause SoB

Heart sounds audible,

murmurs more

common

Chest is clear in CCF,

in acute LVF bilateral

basal creps of pulm

oedema

Pulmonary

disease

AFib uncommon

Heart sounds

quiet, murmurs

uncommon

Usually there are

bilateral signs in

COPD, unilateral

in pneumonia

Examination

Crepitations or

crackles

Heart failure

Acute LVF bilat fine

inspiratory crepitations

Pulmonary

disease

Pulm fibrosis-

medium end-insp

crackles

Infection/COPD–,

coarse localised

crackles

Atrial Flutter

Atrial Flutter

Atrial Fibrillation

Lifetime risks for development of AF are 1 in 4 for men

and women 40 years of age and older

62

Follow-up of 3,999 men and 4,726 women from 1968 to 1999,

i.e. 176,166 person-years (Framingham Heart Study)

40

0

26.0%

Lif

etim

e ri

sk f

or

AF

(%

)

50 years40 years

30

20

10

70 years60 years 80 years

Index age

25.9% 25.8%24.3%

22.7%23.0% 23.2% 23.4%23.0%

21.6%

Men

Women

Adapted from Lloyd-Jones et al. Circulation 2004;110:1042–6.

The Treatment of all TachyArrhythmias

is:-

Beta Blockers - NICE guidance

Which Beta Blockers – BISOPROLOL and NEBIVOLOL

Atrial Fibrillation – Beta blockers and rarely-Catheter Ablation

Atrial Flutter – Beta blockers and occasionally-Catheter Ablation

Atrial Tachycardia – Beta blockers and Catheter Ablation

SVT – Catheter Ablation and Beta Blockers

VT and VF – Beta blockers and Implantable Cardiovertor Defibrillators (ICD) and occasionally Amiodarone

Those pts who can’t take BB there is Catheter Ablation or Ca2+ blockers

AFib ? Rate or Rhythm ?NICE guidance, AFFIRM trial, RACE trial

1st priority – RATE CONTROL

2nd priority – Anticoagulation

Risk assessment using CHADS2 score (or CHA2DS2-VASc)C – Congestive Cardiac Failure eg impaired LV function – 1point

H – Hypertension, uncontrolled – 1pt

A – Age>65 yrs – 1pt

D – Diabetes Mellitus – 1pt

S – Stroke or TIA - 2 pts

VASc – vascular disease – 1 point

A – age>75 yrs – 2 pt

S – sex - female – 1 pt

1 Point = nil or consider OAC if other risk factors eg obesity+/- OSA

2 points = recommend OAC, (? all women over 65yrs ?)

Answer:- Rate control

Rate control: - for the vast majority of AFib pts

- Pts over 65 yrs - NICE

Rhythm control:- for <15% of AFib pts

Young pts under 65 yrs, with NO other cardiac

conditions eg valves or hypertension

Echo routinely for pts <65yrs or with murmur

Rate & Rhythm drugs for AFib

Rate control:- Aim for resting heart rate of <70 bpm in AFib

1st Beta Blocker or Calcium antagonist (Diltiazem)

2nd BBlocker + Digoxin or Diltiazem(Slozem) + Digoxin

NOT Amiodarone

Rhythm control:- Aim for Sinus Rhythm most of time

1st Standard Beta blocker eg Bisoprolol

2nd Sotalol or Amiodarone both class III AARx

3rd Dronedarone – monthly LFTs for 6 months then at 9, 12

4th Flecainide ONLY in norm LV; Cardiologist use ONLY

NB Dronedarone is not compatible with Dabigatran

Rate & Rhythm drugs for AFib

Rhythm control:-

“Pill in the Pocket”

For Paroxysmal / Persistent AFib

Usually in younger pts <60yrs with structurally normal hearts

Bisoprolol, Flecainide, Sotalol or Dronedarone started at onset of symptoms and stopped when AFib stops

Flecainide is NOT for use in pts with ANY structural heart disease apart from mild Mitral Regurg

Admission Criteria

AFib with angina at rest

AFib with heart failure

AFib with ventricular rate > 150 bpm

Otherwise Primary care with initial:-Rate control + Anticoagulation

eg Bisoprolol + Nothing OR

Bisoprolol + dOAC/Warfarin see CHA2DS2-VASc score

Refer to Cardiology OPD if appropriate for

Rhythm control and DC Cardioversion

Electrical DC Cardioversion of AFib

Patients unsuitable for DC Cardioversion:-- Elderly patients >65-70 yrs – (NICE)

- Pts with contraindication to anticoagulation

- Unfavourable cardiac features eg Lt Atrium> 5.5cm, Mitral Valve

- Long duration of AFib eg >12 months

- Multiple relapses while on AntiArrhythmic treatment (AARx)

- Thyrotoxicosis untreated

After successful DC Cardioversion:-

60% of pts will have relapsed into AFib by 1 year

despite appropriate AARx

Valvular or not Valvular AFibTable 1 Valvular indications and contraindications for dOAC therapy in AF patients

Contra-indicated:-

Mechanical (metal) prosthetic valve

Moderate to severe mitral stenosis (usually of rheumatic origin)

Eligible:-

Moderate other native valvular disease (+/-severe – not Europace data)

Severe aortic stenosis, Limited data, Most will undergo intervention

Bioprosthetic (tissue)valve (except for the first 3 months post-operatively)

Mitral valve repair, (except for the first 3–6 months post-operatively)

PTAV and TAVI (but no prospective data; may require combination

with single or double antiplatelets: consider bleeding risk)

Hypertrophic Cardiomyopathy (but no prospective data)

{TAVI, transcatheter aortic valve implantation. PTAV, percutaneous transluminal aortic

valvuloplasty; }

doi:10.1093/europace/euv309 Heidbuchel H. EHRA Practical guidance Aug 2015

direct Oral AntiCoagulants

Dabigatran – RE-LY 18000 pts 2yr fup

reduction in mortality 12%, rel. risk reduction 35%

reduction in ischaemic AND haemorrhagic stroke

Apixaban – Aristotle 18000 pts 1.8 yr fup

reduction in mortality 11%, rel. risk reduction 22%

reduction in haemorrhagic stroke only

Rivaroxaban – Rocket-AF 14000 pts 1.9yr fup

No reduction in mortality or stroke vs. warfarin

direct OAC trialsDabigatran – RE-LY 18000 pts 2yr fup - superior to warfarin

Twice daily (drug half life 14-17 hrs effect on thrombin)

Reduced dose in chronic renal failure (CKD eGFR <60)

Contra-indicated in severe CKD eGFR <35

80% renal excretion

Licensed for AFib and VTE Rx

Apixaban – Aristotle 18000 pts 1.8 yr fup - superior to warfarin

Twice daily (drug active for 9 -14hrs factor Xa slowly returns to normal)

Contra-indicated in severe CKD eGFR <20

25% renal, 75% liver/gut

Licensed for AFib and VTE Rx

Rivaroxaban – Rocket-AF 14000 pts 1.9yr fup – not superior to warfarin

Once daily (drug active for 8 -12hrs factor Xa slowly returns to normal)

Reduced dose in chronic renal failure (CKD eGFR <60)

Contra-indicated in severe CKD eGFR <20, reduced dose eGFR 20-60

66% renal, 33% liver metabolism

Licensed for AFib and VTE Rx

Edoxaban - Engage AF-TIMI 48 21000 pts, 2.8yr fup – not superior to warfarin

Bleeding with dOACs

Highest bleeding rates(non fatal) seen with

Rivaroxaban 15 or 20mg od

Lowest bleeding rates Dabigatran 110 mg bd

Reversal of anticoag – Dabigatran –yes

Rivaroxaban, Apixaban, Edoxaban – not yet

Drug interactions with dOACs

CYP inhibitors (Cytochrome P450)

ciclosporin, dronedarone, erythromycin, or ketoconazole

result in increased concentration of nOACs – use the lower dose

Dabigatran + Dronedarone are contraindicated

Caution in

CYP inducers

rifampicin, phenytoin, carbamazepine, phenobarbital or St John’s Wort, may result in a lower concentration – use the higher dose

Avoid concomitant use with :-

higher dose aspirin or chronic NSAIDs,

SSRIs - sertraline, citalopram have similar bleeding risk as aspirin 75mg, - use lower dose dOACs lower bleeding risk eg Dab/Apix

HAS-BLED scoreH – Hypertension, BP > 160 sys

A,A,A – Abnormal Renal, Liver and Age >65 yrs, 1 pt each

S – Stroke - previous

B – Bleed – previous

L – Labile INR

E – ?

D – Drugs and Alcohol

Score of ≥3 tips balance of risk of bleed at 1 yr vs.

benefit of anticoag

HAS-BLED predates nOACs - refers to Warfarin

Electrical DC Cardioversion of AFib

Patients unsuitable for DC Cardioversion:-- Older patients >65 yrs – (NICE)

- Pts with contraindication to anticoagulation

- Unfavourable cardiac features eg Lt Atrium> 5.5cm, Mitral Valve

- Long duration of AFib eg >12 months

- Multiple relapses while on AntiArrhythmic treatment (AARx)

- Thyrotoxicosis untreated

After successful DC Cardioversion:-

60% of pts will have relapsed into AFib by 1 year

despite appropriate AARx

Pts appropriate for nOACs

- AFib patients (non-valvular),

Pts over 75 yrs

Pts over 65 yrs + DM, HT, impaired LV

Pts with AFib&TIA, or TIA/Stroke on Warfarin

Pts with poor Warfarin control or intolerant

Catheter Ablation for AFib

1- Ablation of AVNode causing Heart Block (Pts>70yrs)

& Permanent Pacemaker -

(usually reserved for elderly - drug intolerant pts)

2- Pulmonary Vein Isolation, PVI (Pts <50/55yrs)

Low success rate <50% - 1 procedure; most need 2 procs >65% succ

Long term success poor - 4 years post PVI < 40% in SR

High recurrence rate of AFib > 10% pa

Procedures are high risk – 4% SERIOUS complications +

Cerebral Infarcts 4 - 6 mm in size (asymptomatic) in 8-30% of pts

Very few Cardiologists would have this procedure – straw poll at AHA / ESC

Catheter Ablation for AFib

1- Ablation of AVNode causing Heart Block (Pts>70yrs)

& Permanent Pacemaker -

(usually reserved for elderly - drug intolerant pts)

2- Pulmonary Vein Isolation, PVI (Pts <50/55yrs)

Low success rate 33% - 1 procedure; most need 2 procs

Long term success poor - 4 years post PVI < 40% in SR

High recurrence rate of AFib > 10% pa

Procedures are high risk – 6% SERIOUS complications + 8-30% of patients have asymptomatic Cerebral Infarcts 4 - 6 mm in size

Very few Cardiologists would have this procedure – straw poll at AHA / ESC

PVI Ablation

Pt selection is key

Age <55yrs :: if older > very high recurrence rate (vhrr) eg 70%

Paroxysmal AFib only :: if permanent/chronic – vhrr

Normal :: if Hypertension, Thyroid, Alcohol, –vhrr

Normal Heart :: if any Valves or Cardiomyopathy – vhrr

1 procedure 12 months success 33%, 5 yr -20% are still in SR

2 procedures 12 month success 60-65%, 4yr – <40% are still in SR

Procedural risks are high 4-6% SERIOUS incl Death, + 8-30% silent

cerebral infarcts for EACH procedure