• Also called hypoplastic right heart syndrome.

Embryology

• May be due to fetal endocarditis during late gestation.

Pathology

• Pulmonary atresia-
  • 75%- valvular/membranous
  • 25%- infundibular/muscular
• Right ventricle-
  • RV components-
    • Tripartite- 58% (inlet, apex and outlet)
    • Bipartite- 34% (only inlet and outlet)
    • Unipartite- 8% (only inlet)
    • Note that in unipartite and bipartite types, all three components of RV are actually present, but there is muscle overgrowth in some components.
  • RV size-
    • Usually small.
    • Dilated RV in 10%- due to tricuspid regurgitation, in some cases due to Ebstein’s anomaly.
• Tricuspid valve-
  • Corresponds to RV size
  • Usually hypoplastic
  • Sometimes (10%) dilated, leading to severe TR. In some cases, this is due to Ebstein’s anomaly.
• Pulmonary artery-
  • Usually confluent.
  • Usually normal or mildly hypoplastic. Moderate or severe hypoplasia in 6%.
• ASD-
  • Usually large enough for unobstructed blood flow from right atrium to left atrium
• Ductus-
  • Pulmonary circulation is maintained by a patent ductus. If it closes, death will occur.
  • There are no aortopulmonary collaterals (MAPCAs support pulmonary circulation in pulmonary atresia with VSD and hence there is only mild cyanosis)
  • Obtuse angle between ductus and proximal aorta (normal)- late onset pulmonary atresia; acute angle- early onset.
• Coronary anomalies
  • Communications between right ventricle and coronary arteries. RV- thick walled myocardial spaces- distended capillaries- coronary artery.
  • The term sinusoids is pathologically incorrect. Ventriculo-coronary arterial connections or VCC is correct.
  • Mainly located at RV apex.
  • More likely in small right ventricles, especially in monopartite.
  • Cause is non-regression of embryonic channels due to high RV pressure.
  • VCC causes myocardial ischemia due to coronary steal- causes RV and LV ischemia.
  • Even if no VCC is present, high RV luminal pressure decreases coronary flow to RV causing RV ischemia leading to RV fibrosis.
  • Types of coronary circulation (judged by coronary opacification during right ventricular angiography)-
    • No opacification- 58%
    • Mild opacification- 15%
    • Major opacification, but antegrade coronary flow from aorta preserved- 17%
    • Major opacification with coronary atresia or significant stenosis- 8%
  • RV dependent coronary circulation-
    • Atresia or severe stenosis of proximal coronary artery- RV decompression (during repair) would cause myocardial ischemia due to inadequate pressure to drive coronary flow.
    • No coronary stenosis, but coronary is ectatic- RV decompression would cause coronary steal through the dilated vessel into the RV.

Classification-

• Greenwold classification-
  • Type I- small right ventricle
  • Type II- large right ventricle with tricuspid regurgitation
• Bull and de Leval classification-
  • Group I- tripartite RV
  • Group II- bipartite RV
  • Group III- unipartite RV
• Milliken classification (surgically oriented)-
  • Mild, moderate or severe hypoplasia of tricuspid annulus, RV cavity and RVOT.

Hemodynamics

• Fetus-
  • Foramen ovale is large to accommodate increased flow.
  • Ductus carries blood from aorta to pulmonary artery (reverse of normal).
  • Ductus carries only 10% of cardiac output (normal 60%).
• After birth-
  • RV pressure is high (suprasystemic).
  • No TR.
  • Blood that enters RV goes out through coronaries- circular shunt (as this drains back to RA).
  • RA is enlarged.
  • RA pressure is more than LA pressure- flow across non-restrictive ASD.
  • LA and LV are dilated.
  • Blood enters pulmonary circulation via ductus in newborn.
  • Ductus closes at normal time- profound cyanosis- death.
  • With significant TR, RV dilates and RV pressure is subsystemic.

Clinical features

• Cyanosis noted at birth. Cyanosis worsens in first or second day. Tachypnoea and metabolic acidosis culminating in death.
• No precordial activity, no murmurs (sometimes closing ductus murmur).
• Type II- RV activity, PSM of TR.

Natural history

• Severe TR- hydrops fetalis.
• 50% are dead by 2 weeks.
• 85% are dead by 6 months.

ECG

• Adult precordial pattern in neonate (no RV, LV prominence)- also seen in tricuspid atresia.
• QRS axis is +30⁰ to +90⁰ – helps to distinguish from tricuspid atresia where there is left axis deviation.

Chest X-ray

• Pulmonary arteries appear normal or mildly hypoplastic.
• Cardiomegaly only in type II.
• Decreased pulmonary blood flow.
• Aortic arch is always left sided. (Right aortic arch is present in 25 – 50% of PA with VSD)
• DDs of massive cardiomegaly with decreased pulmonary blood flow-
  • Ebstein’s anomaly
  • PA with IVS type II
  • Uhl’s anomaly

Echocardiography

• Thick membrane at pulmonary valve level with no flow across it.
• RV is hypoplastic. RV endocardium shows deep invaginations which may or may not communicate with coronaries.
• RA is dilated
• There is right to left shunt across ASD
• There is a ductus with left to right shunt
• Type II has to be carefully distinguished from Ebstein’s anomaly (functional pulmonary atresia).
• Surgical importance-
  • RV components
  • Tricuspid valve Z-score

Cardiac catheterization

• Always needed to look for
  • RV morphology
  • VCC and coronary stenosis/atresia and
  • PA anatomy.
• RA pressure is higher than LA pressure.
• Same oxygen saturations in venacavae, RA and RV.
• Same oxygen saturations, though lower than normal, in LA, LV and aorta.

Management

• Start PGE1 0.1 μg/kg/min.
• Then do cath study. Then plan further strategy based on RV type and sinusoids
• Tripartite RV and bipartite RV-
  • Neonate- BT shunt + RV-PA connection (transannular RVOT patch/closed valvotomy/percutaneous laser)
  • 6 to 18 months-
    • TV Z-score > -2 and arterial oxygen saturation > 70% with BT shunt occlusion
      • Yes- Two ventricular repair (RVOT reconstruction + closure of BT shunt)
      • No- One and a half ventricular repair (BDG + RVOT reconstruction)
• Monopartite RV and any type RV with RV dependent coronary circulation-
  • BT shunt- BDG or Hemi-Fontan- Fontan
• Coronary atresia- Cardiac transplantation
• Type II- Cardiac transplantation or Starnes’ procedure (convert to tricuspid atresia, then BT – BDG- TCPC)

• Mitral valve apparatus-
  • Papillary muscles
  • Chordae tendineae
  • Leaflets
  • Annulus
• Common causes of MR-
  • Rheumatic
  • MVP
  • CAD
  • Cardiomyopathy (dilated, hypertrophic)
  • IE
  • Annular calcification
• List of causes of MR-
  • Papillary muscles-
    • CAD (ischemia, MI)
    • Severe anemia
    • Shock
    • Amyloidosis
    • Sarcoidosis
    • Abscess
    • Granuloma
    • Neoplasm
    • Dilated cardiomyopathy
    • Trauma
    • Rupture (MI)
    • Parachute mitral valve
  • Chordae tendineae-
    • Idiopathic rupture
    • Myxomatous degeneration (MVP, Marfan syndrome, Ehlers-Danlos syndrome, Pseudoxanthoma elasticum)
    • Osteogenesis imperfect
    • Relapsing polychondritis
    • IE
    • Acute LV dilation due to any cause
    • Acute rheumatic fever
    • Blunt chest trauma
    • Following PTMC
  • Leaflets-
    • Rheumatic
    • Myxomatous degeneration (MVP, Marfan syndrome, Ehlers-Danlos syndrome, Pseudoxanthoma elasticum)
    • IE
    • SLE
    • Scleroderma
    • Mitral valve clefts or fenestrations
    • Trauma
    • Following PTMC
    • Atrial myxoma
  • Annulus-
    • Abscess (IE)
    • Annular calcification
    • Dilation of annulus- dilated cardiomyopathy
    • LV submitral aneurysm
  • Other causes-
    • SAM- HCM
    • Prosthetic valve-
      • Suture interruption due to surgical technique or IE
      • Strut fracture
      • Immobilized disc
      • Immobilized ball
      • Biological valve cusp perforation or degeneration
    • Hypereosinophilic syndrome
    • Endomyocardial fibrosis
• Associations of parachute mitral valve-
  • Endocardial cushion defects
  • Endocardial fibroelastosis
  • TGA
  • Anomalous origin of left coronary
• Causes of MR in IE-
  • Leaflet perforation
  • Vegetations preventing leaflet coaptation
  • Chordal rupture
  • Annular abscess
  • Chordal rupture
  • Valve retraction during healing phase
• Causes of MR in RHD-
  • Leaflet rigid and retracted
  • Chordae shortened
• Causes of MR in blunt chest trauma-
  • Leaflet damage
  • Chordal rupture
• Mitral annulus
  • Normal diameter is 10 cm
  • Normally constricts during systole
• LV submitral aneurysm-
  • Sub-Saharan Africa
  • Posterior
• Mitral annular calcification-
  • More in women
  • Risk factors for development- HT, DM, DLP
  • Increases morbidity and mortality due to associated coronary and carotid atherosclerosis
  • Causes-
    • Atherosclerosis
    • Marfan syndrome
    • Hurler syndrome
    • CRF
    • Hyperparathyrodism
    • Rheumatic heart disease
  • Mechanism of MR-
    • Lack of systolic constriction
    • Immobilization of leaflets
  • May involve conduction system- AV block, IVCD
• Chordal rupture is more common in the posterior chordae
• Posterior papillary muscle gets ischemic more commonly than the anterior one as it gets only one supply (PDA) while the latter gets two (LAD & LCx).
• Causes of MR in CAD-
  • RWMA causing tethering of PML
  • Papillary muscle ischemia
  • LV failure (see below)
• Causes of MR in LV failure-
  • Alteration of spatial relation between papillary muscles
  • Annular dilation
  • Poor annular systolic constriction
• Ischemic MR has poorer prognosis than other causes of MR- due to associated ischemia

Pathophysiology

• Factors determining regurgitant volume-
  • Regurgitant orifice
  • LV-LA pressure gradient
• Regurgitant orifice can be increased by-
  • Increasing preload
  • Increasing afterload and
  • Decreasing LV contractility
• LV-LA pressure gradient can be increased by increasing SVR.
• 50% of MR occurs before aortic valve opening

  The progression of an MR with a regurgitant fraction of 50% are shown below.

  	EDV	ESV	EF	TSV	FSV	LAP
  N	120	50	60	70	70	10
  a/c MR	140	40	70	100	50	25
  c/c MR	200	60	70	140	70	15
  c/c MR decom	220	100	55	120	60	25

• In acute phase, LA is non-compliant. This allows only a slight increase in EDV. ESV is decreased, though only slightly, due to low afterload as LV is able to eject into the LA which is low pressured compared to the aorta. The total stroke volume increases to a lesser degree than it does in chronic MR where the large EDV due to the compliant LA leads to a large increase. Since TSV increases only slightly, forward stroke volume falls.
• In the chronic phase, LA compliance increases and hence EDV rises. ESV rises to normal. The high EDV allows normal forward stroke volume.
• In longstanding cases, LV may decompensate due to prolonged hemodynamic overload. Then, due to incomplete LV emptying ESV increases. Also, due to drop in total stroke volume, forward stroke volume decreases.

  The changes in preload and afterload are as below.

  	Preload	Afterload
  N	N	N
  a/c MR	Increase	Decrease
  c/c MR	Increase	N
  c/c MR decom	Increase	Increase

• In all phases of MR, preload is increased due to increase in EDV. In acute MR, the increase is slight, in chronic MR there is a prominent increase while in chronic decompensated MR, it increases further as EDV increases further.
• Afterload is decreased in acute MR due to ejection into the LA which has lower pressure compared to the aorta. In chronic MR, due to LV dilation, the afterload increases to normal. In decompensated chronic MR, it increases to above normal.
• LV wall tension is very low in acute MR while in chronic compensated MR it is normal or high.
• MR begets MR due to increased EDV causing annular dilation.
• Myocardial oxygen demand is not much increased in MR due to normal wall tension. So myocardial ischemia is less likely in MR than in AR or AS.
• In MR, due to reduced afterload, EF is increased (EF is afterload dependent). So EF less than 60% indicates LV dysfunction.
• Increased ESV/ESD is another indicator of LV dysfunction in MR.
• LA pressure-
  • Tall v wave
  • Rapid y descent (unless coexistent MS)
  • Early diastolic pressure more than LV pressure (reason for mitral MDM)
  • Late diastolic pressure less than LV pressure (higher if coexistent MS)
  • Higher LA pressure in acute MR than in chronic MR
• LA compliance-
  • Normal or reduced-
    • Usually seen in acute MR
    • Hypertropied atrial wall
    • PVR increases in 6 to 12 months
  • Marked increase -
    • Usually seen in chronic severe MR
    • Atrial wall has little muscle, more fibrous tissue
    • PVR normal
    • AF always present
    • COP may be low
    • Moderate increase-
  • Commonest group

Symptoms

• Fatigue- due to low cardiac output
• Dyspnoea- more likely in acute MR and in chronic decompensated MR
• Right heart failure symptoms like ascites and edema- more likely in acute MR and in chronic decompensated MR
• It is important to understand that chronic MR may become symptomatic only after the onset of irreversible LV dysfunction.
  

Physical examination

• Sharp upstroke of pulse
• Hyperdynamic LV apex
• Palpable S3 may be present
• Parasternal late systolic impulse due to LA enlargement
• If leaflet disease is the cause of MR- soft S1
• Wide split S2- due to early A2 due to reduced LVET
• Loud P2 if PAH
• S3 – not a sign of heart failure in MR
• Mitral MDM- not a sign of heart failure in MR
• PSM-
  • Begins with S1 and extends beyond A2
  • Flat topped
  • High pitched & blowing
  • Radiates to left axilla or base (PML prolapse) or spine (AML prolapse)
  • No change with AF or VPCs
  • Little correlation between intensity of murmur and severity of MR
• Severe MR with soft or no murmur- silent MR-
  • LV dilation
  • Acute MR
  • Paraprosthetic MR
• Late systolic murmur-
  • Seen in MVP and papillary muscle dysfunction
  • Usually MR is not severe
  • S1 is not soft
• Early systolic murmur-
  • Acute MR (due to large LA v wave)
• Dynamic auscultation-
  • Non-MVP MR murmur is distinguished from MVP murmur by increase with squatting and decrease with standing (opposite with MVP).
  • MR murmur is distinguished from AS/HCM murmur by increase with isometric handgrip (opposite for AS/HCM).

Echocardiography

• Mitral annular calcification is seen between mitral valve apparatus and posterior wall.
• TEE is useful to see if repair is possible in MVP.
• Features of severe MR-
  • Effective regurgitant orifice 0.4 cm2 or more
  • Regurgitant volume 60 ml or more
  • Regurgitant fraction 50% or more
  • MR jet reaching LA posterior wall (with high aliasing velocity of course!)
  • Pulmonary vein systolic flow reversal
• MVP is defined as more than 2 mm systolic displacement of mitral leaflet into LA

ECG

• LAE, LVE

Radiography

• LAE (more than in MS)
• Interstitial edema is seen with acute MR, chronic decompensated MR or with coexistent MS.
• Annular calcium is seen as a C shaped opacity in posterior third of heart in lateral or RAO.

Cardiac MRI-

• Useful for MR quantification when echo is suboptimal

LV angiography-

• Qualitative estimation of MR- by LA opacification
• Quantitative estimation of MR- by finding total stroke volume from LV angio and forward stroke volume by Fick method; then the difference is found

Disease course

• Asymptomatic severe MS-
  • Yearly risk of cardiac death- 4%
  • 5 year chance of needing surgery- 30%
  • 10 year chance of needing surgery- almost all
  • Main series- Sarano, Rosenhek, Rosen
• MR needing surgery, but not undergoing surgery- 5 year survival is 30% – Horstkotte
• Poorer outcome in MR due to flail leaflet- annual mortality rate of 6.3%- Ling

Medical management

• Acute MR- afterload reduction with nitroprusside.
• Chronic MR- ACE inhibitors and nifedipine are used, but have not been proven to be effective in studies.

Surgery-

• Conditions in which repair of mitral valve is possible-
  • MVP
  • Chordal rupture
  • Papillary muscle dysfunction
  • Annular dilation
  • Leaflet perforation due to IE
  • Rheumatic MR in the young
• Steps of mitral valve repair in PML prolapse-
  • Reduction excision of posterior leaflet
  • Reattachment of posterior leaflet
  • Repair of posterior leaflet
  • Insertion of annuloplasty ring
• Annuloplasty ring-
  • As part of MVP repair
  • For MR due to dilated cardiomyopathy
  • For MR due to regional LV dysfunction with annular dilation
• Disadvantages of mitral replacement-
  • LV dysfunction due to loss of annular-chordal-papillary muscle continuity
  • IE risk
  • Mechanical prosthesis- thrombus, hemorrhage
  • Bioprosthesis- deterioration
• Operative mortality (STS database)-
  • Repair- 2%
  • Replacement- 6%
  • Replacement with CABG- 10 to 13%
  • Replacement in elderly- 14%
• Percutaneous mitral repair-
  • Edge to edge technique
  • Coronary sinus approach to mitral annuloplasty
• MV repair or replacement in MR with LV dysfunction-
  • Improvement in LV function- usual
  • Same LV function- less common
  • Deterioration of LV function- uncommon
• Indications for surgery-
  • Symptoms present-
    • EF > 30% + ESD ≤ 55 mm (class I)
    • EF < 30% or ESD > 55 mm + chordal preservation possible (class IIa)
  • No symptoms-
    • EF ≤ 60% (class I)
    • ESD ≥ 40 mm (class I)
    • New onset AF (class IIa)
    • Pulmonary HT (class IIa)
    • Successful MV repair highly likely (class IIa)

Acute MR

• Clinical features
  • Murmur-
    • Decrescendo- ends before A2
    • Low pitched
    • Soft
  • LV S4
  • PAH is common
  • PA v wave may cause early P2 leading to paradoxical split of S2
• Echo-
  • Severe MR jet
  • No LA or LV dilation
  • Prominent systolic motion of LV
• Medical management-
  • Afterload reduction with IV nitroprusside
  • If hypotension, all dobutamine also
  • IABP
• Surgery-
  • Needed as an emergency
  • If MI is causing papillary muscle dysfunction, if possible, defer surgery for 4 to 6 weeks. For rupture, immediate surgery is needed.

	Trial	Population	Arm 1	Arm 2	Arm 3	Result
PCI vs Med
	ACME	Single or multivessel CAD	PCI	Med		Same
	MASS	Proximal LAD	PCI	CABG	Med	Same
	RITA-2	Stable angina	PCI	Med		Death or MI higher with PCI.
	COURAGE	Single or multivessel CAD	BMS	Med		Same
	OAT	Post MI 3 to 28 days, asymptomatic high risk cases	PCI	Med		Same
PCI vs CABG
	EAST	Multivessel	PCI	CABG		Same
	BARI	Multivessel	PCI	CABG		Same. DM- CABG better survival.
	ARTS	Multivessel	BMS	CABG		Same. More revascularisation with PCI. DM- CABG better survival.
	ARTS-2	Multivessel	DES	CABG		Same. Equal revascularisation with PCI when compared to ARTS CABG group.
	SoS	Multivessel	PCI	CABG		More mortality and revascularisation in PCI.
	ERACI II		PCI	CABG		Less death or MI with PCI. More revascularisation with PCI.
	SYNTAX	LMCA & TVD	PES	CABG		1 year follow-up. LMCA- Major adverse cardiac or cerebrovascular events equal. More revascularisation in PCI. TVD- Both MACCE & revascularisation more in PCI. Both LMCA & TVD- Both MACCE & revascularisation more in PCI.
	PRECOMBAT	LMCA	SES	CABG		Ongoing. Korea.
CABG vs Med
	CASS		CABG	Med		CABG better.
	ECSS		CABG	Med		CABG better.
	VACS		CABG	Med		CABG better.
Medical
	Antiplatelet trialists’ collaboration	Aspirin				Decreases mortality
	CHARISMA	Stable angina	Dual antiplatelet	Aspirin		Same
	CAPRIE	Stable angina	Clopidogrel	Aspirin		Clopidogrel was better than aspirin
	HOPE	Stable angina	Ramipril	Placebo		Ramipril was better than placebo.
	EUROPA	Stable angina	Perindopril			Perindopril was useful.
	WHI	Stable angina	HRT in postmenopausal women			Harmful
	BEAUTIFUL	Stable angina and systolic dysfunciton	Ivabradine	Placebo		With heart rate more than 70/mt, ivabradine reduces coronary endpoints. Considering all patients, there was no benefit.
	INITIATIVE	Stable angina	Ivabradine	Atenolol		Similar

]]> http://www.heartpearls.com/2010/05/stable-angina-clinical-trials.html/feed 0 http://www.heartpearls.com/2010/04/aortic-regurgitation.html http://www.heartpearls.com/2010/04/aortic-regurgitation.html#comments Tue, 27 Apr 2010 14:29:03 +0000 Dr Jayachandran Thejus MD http://www.heartpearls.com/2010/04/aortic-regurgitation.html Etiology and pathology

• Valvular disease
  • Common causes-
    • Rheumatic
    • Bicuspid aortic valve
    • Calcific aortic valve disease (usually AR is mild)
    • Infective endocarditis (cusp damage, vegetation interfering with coaptation)
    • Trauma (ascending aortic tear causes cusp prolapse)
    • Large VSD
    • Membranous subaortic stenosis
  • Less common causes-
    • After percutaneous balloon valvulotomy
    • Myxomatous degeneration of aortic valve
    • Congenital AR- unicommissural, quadricuspid
    • Rupture of congenitally fenestrated valve (usually due to hypertension)
    • Connective tissue disease- SLE, RA, AS, Takayasu, Whipple, Crohn, Jaccoud arthropathy
    • Anorectic drugs
• Aortic root disease-
  • Root dilation-
    • Marfan syndrome
    • Cystic medial necrosis other than Marfan
    • Bicuspid aortic valve
    • Syphilis
    • Hypertension
    • Age related
    • Connective tissue disease- ankylosing spondylitis, osteogenesis imperfecta, Behcet syndrome, psoriatic arthritis, ulcerative colitis with arthritis, relapsing polychondritis, reactive arthritis, GCA
    • Appetite suppressants
    • AR itself may increase AR due to ascending aortic dilation- AR begets AR
  • Root dissection

Chronic AR

Pathophysiology

• Preload is increased due to-
  • Increased EDV
  • (Note- Preload is the tension in the myocardium just before contraction- correlates with EDV)
  • (Note- Tension from Wikipedia-In physics, tension is the magnitude of the pulling force exerted by a string, cable, chain, or similar object on another object. It is the opposite of compression. As tension is the magnitude of a force, it is measured in newtons and is always measured parallel to the string on which it applies)
• Afterload is increased due to-
  • Increased LV systolic pressure and
  • LV dilation
  • (Note- Afterload is the tension in the myocardium during contraction- it is proportional to PR/h where P is ventricular pressure, R is radius of ventricle and h is wall thickness)
• Myocardial ischemia occurs due to-
  • Increased myocardial oxygen demand due to-
    • Increased afterload
    • Increased LV ejection time
    • Increased LV mass
  • Decreased myocardial oxygen supply due to-
    • Decreased aortic diastolic pressure
    • Decreased diastolic filling time due to increased LV ejection time
    • Decreased effective stroke volume
• LV dysfunction occurs due to-
  • Increased afterload
  • Myocardial ischemia and
  • Increased LV mass
• LV mass increase in AR-
  • Due to replication of sarcomeres in series and due to increased interstitial connective tissue
  • The increase is more than that in AS
• Systolic wall stress in AR-
  • Initially, increased LV wall thickness (stress α tension/wall thickness) does not allow stress to increase in spite of increased afterload
  • Later, thickness cannot increase further to cope up with increased afterload. This is called afterload mismatch.
• In AR, forward stroke volume does not fall due to-
  • Increased stroke volume to compensate for the leak (this occurs due to increased EDV)
• In AR, LV is able to overcome the increased afterload due to-
  • Increased preload (Frank- Starling—increased preload increases contractility) and
  • LV hypertrophy (more muscle mass to contract)
• LVEDP in AR-
  • Compensated phase- normal due to
    • Complete LV emptying (as LV function is compensatorily increased to deal with the increased afterload)
    • Increased LV compliance.
  • Decompensated phase- increased due to
    • Incomplete LV emptying (as LV function is not good enough for the increased afterload)
    • Decreased LV compliance due to interstial fibrosis
• ESV in AR-
  • Compensated phase- normal due to complete LV emptying
  • Decompensated phase- increased due to incomplete LV emptying
• Exercise in AR-
  • Compensated phase- Forward cardiac output usually increases efficiently without increase in LVEDP. The reasons are-
    • Decrease in SVR causes less AR
    • Diastole shortens (compared to systole) causing less AR
  • Decompensated phase- Failure to generate adequate cardiac output (fatigue on exertion). Increase in LVEDP (dyspnoea on exertion).

Symptoms

• Palpitations
  • Occurs before LV dysfunction occurs unlike the other symptoms
  • Due to increased EDV
  • More on lying down
  • More after a VPC
• Fatigue, dyspnoea and angina
  • Occurs after LV dysfunction occurs
  • Angina may be nocturnal due to lower heart rate at night (more AR)

Physical examination

• Eponyms in AR-
  • Common-
    • de Musset sign- head nodding
    • Water-hammer pulse or Corrigan pulse or collapsing pulse- high volume pulse with quick ascent, ill sustained peak and quick collapse. Palpate in radial artery with arm elevated.
    • Bisferiens pulse- best palpated in brachial or femoral arteries.
    • Pistol shot sounds or Traube sign- femoral artery distal compression produces double sounds (systolic and diastolic)
    • Muller sign- systolic pulsation of uvula
    • Duroziez sign- femoral artery- systolic murmur with proximal compression and diastolic murmur with distal compression
    • Quincke sign- pressure on tip of fingernail, fingertip transillumination or glass slide on lip
    • Lighthouse sign- flushing and blanching of forehead
    • Landolfi’s sign- papillary constriction and dilation
    • Becker’s sign- retinal vessel pulsation
    • Rosenbach’s sign- liver pulsation
    • Gerhardt’s sign- splenic pulsation
    • Hill’s sign or popliteal-brachial gradient- Popliteal BP 20 mmHg more than brachial BP.
  • Uncommon-
    • Morton and Mahon sign- same as lighthouse sign
    • Ashrafian sign- pulsatile pseudoproptosis
    • Bozzolo sign- pulsatile nasal mucosa
    • Drummond sign- systolic expulsion of air from nose when mouth is closed
    • Mayen’s sign- when arm is raised, diastolic BP drops by more than 15 mmHg
    • Penny sign- flushing of wheals
    • Palmar click- pulsating palm
    • Dennison sign, Shelley sign- pulsatile cervix
    • Lincoln sign- popliteal pulsation
    • Sherman sign- dorsalis pedis prominent pulsation in age of 75 yrs or more
    • Other names for collapsing pulse-
      • Watson’s pulse
      • Cannon ball pulse
      • Pulsus celer
      • Rhazes pulse or Al Razi pulse
      • Cuming sign
      • Vieussens pulse
• High volume pulse
• High pulse pressure, high systolic pressure, low diastolic pressure. Beginning of phase IV should be taken as diastolic BP. Diastolic BP is higher in mild AR and in severe AR with heart failure (due to peripheral vasoconstriction).
• Hyperdynamic diffuse apex displaced laterally and inferiorly.
• Parasternal systolic retraction.
• Palpable LVS3
• Systolic thrill at aortic area and over carotids (carotid shudder)
  • (Note- Carotid shudder was initially described by Evans and Lewes in 1945 in AS + AR. Later, in 1976, it was shown by Alpert et al to be present in pure AS and pure AR also. In the same year, Chapman documented it in ascending aortic dissection also. Generally, the term is used in pure AS.)
• S1 may be soft.
• A2-
  • Soft or absent in valvular cause of AR
  • Normal or accentuated in AR due to root dilation (tambour sound)
• S2 split-
  • Paradoxical split can occur (prolonged LVET)
  • Aortic ejection sound may occur due to aortic distension due to increased stroke volume
• LVS3 can occur in pure AR and in AR with LV failure.
• EDM-
  • High frequency
  • Begins with A2
  • Better heard with patient sitting and leaning forward, breath held in expiration.
  • Decrescendo.
  • High pitched in mild AR and rough in severe AR.
  • Early diastolic in mild AR and holodiastolic in severe AR.
  • Late diastolic component is abolished in LV failure due to high LVEDP.
  • Cooing dove murmur in cusp eversion or perforation.
  • Valvular cause of AR- radiation to left sternal border. Root dilation causing AR- radiation to right sternal border.
  • Increased with squatting and isometric exercise
  • Decreased with amyl nitrite and Valsalva
  • Cole-Cecil murmur- EDM radiating to apex and left axilla
• MSM-
  • May be associated with a carotid thrill
  • Higher pitched than the murmur of AS
• Austin Flint murmur-
  • Mid diastolic murmur with presystolic accentuation
  • Seen in severe AR only
  • Causes-
    • AR jet impinging on AML forcing it down thus decreasing mitral orifice
    • Turbulence when AR jet meets mitral inflow jet
    • AML fluttering due to AR jet
    • LV endocardial vibrations due to AR jet
  • With LV failure, due to elevated LVEDP, Austin Flint murmur begins and ends earlier
  • Increased with isometric exercise, reduced by amyl nitrite

Echocardiography

• Points to note-
  • Cause of AR
  • Severity of AR
  • LV function
• High frequency diastolic fluttering of AML- seen in M mode- seen even in mild AR (unlike Austin Flint murmur)
  

  	Mild	Moderate	Severe
  Jet width/LVOT diameter		1/4 to 2/3
  Vena contracta (mm)		3 to 6
  Pressure half-time (ms)	> 700		<250
  LV dilation	Absent	Absent	Present
  Flow reversal in descending thoracic or abdominal aorta	Absent	Absent	Present
  Regurgitant orifice area (cm2)		0.1 to 0.3
  Regurgitant volume (ml)		30 to 60
  Regurgitant fraction		30 to 50

   

• Continuity equation-
  • Regurgitant volume= LVOT flow- mitral flow
  • Regurgitant fraction= Regurgitant volume/ LVOT flow
  • Regurgitant area= Regurgitant volume/ AR TVI
• PISA-
  • Regurgitant area= Flow through aliasing hemisphere surface/AR peak velocity
  • Regurgitant volume= Regurgitant area x AR TVI
  • Regurgitant fraction= Regurgitant volume/LVOT flow
• (Note- In continuity equation, regurgitant volume is calculated first. In PISA, the calculations in order are regurgitant area, regurgitant volume and regurgitant fraction.)

ECG

• High LV voltage
• Q in lateral leads
• Tall upright T waves in lateral leads initially; later strain pattern.

Radiography

• LV enlargement
• LA enlargement if heart failure or mitral valve disease
• Ascending aortic dilation- more than in AS
• Look for ascending aortic aneurysm
• Linear calcifications in ascending aorta- syphilitic aortitis

Angiography

• For assessing AR, contrast injection into aortic root must be at 25 to 35 ml/sec!

Radionuclide angiography

• LV/RV stroke volume ratio > 2 indicates severe AR

MRI

• Can accurately measure severity of AR by measuring regurgitant volume, regurgitant fraction and regurgitant area
• Used when echo is suboptimal

Natural history

• Main studies- Bonow et al, Borer et al
• No symptoms, normal EF-
  • Annual chance of symptoms or LV dysfunction- 6%
  • Annual chance of sudden death- 0.5%
• Angina-
  • Death in 4 years
• Heart failure-
  • Death in 2 years
• Survival and NYHA class in severe AR-
  • NYHA I- 10 yr survival of 75% (equal to general population)
  • NYHA III or IV- 4 yr survival 28%

Medical management

• If diastolic BP is high, vasodilators like nifedipine or ACE inhibitors are to be given
• Beta blockers should be avoided

Surgery

• Indications for surgery in chronic severe AR-
  • Class I-
    • Symptoms
    • Symptoms on TMT
    • EF less than 50% (echo, RVG or MRI)
  • Class IIa-
    • LVESD > 55 mm (50 to 55 is IIb)
    • LVEDD> 75 mm (70 to 75 is IIb)
• Patients with severe LV dysfunction (EF < 25%) before AVR may not have an improvement in LV function after AVR.
• Aortic valve repair-
  • Usually not possible, so AVR will be needed (unlike mitral repair which if often successful)
  • Cusp resuspension or cusp resection for cusp detachment from annulus due to trauma
  • Pericardial patch for cusp perforation in IE
  • Root dilation causing AR-
    • Encircling suture
    • Subcommissural annuloplasty
    • Aortic graft with prosthetic valve- coronaries need to be reimplanted
    • Aortic graft alone
• AVR-
  • Large prosthesis can be implanted as annulus is dilated- so less chance of prosthetic gradient.
  • Operative mortality- 3 to 8%

Acute AR

• Causes-
  • Infective endocarditis
  • Aortic dissection
  • Trauma
• Pathophysiology
  • Normal LV size (not increased as compliance is not increased)
  • Increased LVEDP (dyspoesa) + decreased cardiac output (shock)
  • Increased LVEDP as LV cannot dilate rapid enough to accommodate the regurgitant volume
  • Decreased cardiac output due to-
    • Decreased forward stroke volume because-
      • EDV does not increase as LV compliance does not increase (In chronic AR, increased EDV increases total stoke volume so that forward stroke volume, which is total stroke volume – regurgitant volume, is maintained)
    • Decreased total stroke volume due to-
      • Premature mitral closure due to increased LVEDP
      • Tachycardia (less diastolic filling time). Tachycardia is a compensatory response to decreased cardiac output.
• Physical examination-
  • Hypotension with tachycardia as a compensatory response
  • Dyspnoea due to increased LVEDP
  • Normal pulse pressure
  • No peripheral signs of AR
  • S1 is soft or absent due to premature closure
  • P2 may be loud
  • EDM-
    • Shorter than the murmur of chronic AR (due to rapidly rising LV diastolic pressure)
    • Lower pitched than the murmur of chronic AR (due to rapidly rising LV diastolic pressure)
  • Austin Flint murmur-
    • Shorter than in chronic AR, no presystolic accentuation (due to rapidly rising LV diastolic pressure)
• Echocardiography-
  • AR jet- low end diastolic velocity
  • Mitral valve- late opening and premature closure
  • LV size- normal
  • EF- normal
  • Aortic valve- premature opening
• ECG-
  • Non specific ST-T changes
• Radiography-
  • PVH, pulmonary edema
  • Normal heart size
• Management-
  • Early surgery
  • During preparation for surgery-
    • Dopamine/dobutamine + nitroprusside
    • Do not put on IABP (increased peripheral resistance during diastole increases AR)
    • Do not give beta blockers for tachycardia (increased diastolic interval increases AR)

• Not a thienopyridine

Mechanism

• Inhibition of platelet ADP receptor P2Y12
  • Reversible inhibition
  • More powerful inhibition compared to clopidogrel

Pharmacodynamics

• Onset of effective platelet inhibition- 30 mins
• Normal platelet function after stopping- 2 to 3 days
• No need for activation by hepatic enzymes (so no variability in response unlike clopidogrel which is less effective in 30% cases due to cytochrome P450 variation)

Dose

• Loading dose- 180 mg
• Maintenance dose- 90 mg bid

Trials-

• DISPERSE 2 –
  • Ticagrelor vs clopidogrel
  • Slight decrease in MI and slight increase in bleeding with ticagrelor
• PLATO-
  • The landmark trial for ticagrelor.
  • Ticagrelor vs clopidogrel
  • In STEMI and NSTEMI
  • 12 months follow-up
  • Ticagrelor decreased mortality, MI and stent thrombosis.
  • Stroke risk was similar.
  • Major bleeding not due to CABG was higher with ticagrelor.
  • Ticagrelor produced dyspnoea and bradyarrhythmia.
• ONSET/OFFSET study
  • Stable angina
  • Ticagrelor vs clopidogrel
  • Inhibition of platelet activity was measured
  • Ticagrelor produced more rapid and more powerful platelet inhibition
• RESPOND-
  • Stable angina patients were given clopidogrel and then nonresponders were found by light tranmittance aggregometry.
  • These patients were given ticagrelor or clopidogrel in a 2-way crossover design.
  • Platelet reactivity was decreased to below ischemic risk by ticagrelor in 98 to 100% and by clopidogrel in only 44 to 76% cases.
  • Thus ticagrelor is effective in clopidogrel nonresponders.

• Causes-
  • Bicuspid aortic valve
  • Calcific AS
  • Rheumatic
  • Congenital
  • Atherosclerotic eg type II hypercholesterolemia
  • Rheumatoid
  • Ochronosis (alkaptonuria)

Pathology

• Congenital- Unicuspid valves cause severe AS in infancy.
• Bicuspid aortic valve
  • More in males (3 times more)
  • Some cases are inherited as autosomal dominant
  • NOTCH1 gene mutation in some cases
  • Complications-
    • AR- 20% develop severe AR needing surgery between 10 and 40 years of age
    • AS- Severe AS occurs after 50 years of age. Due to calcification due to turbulence.
    • Infective endocarditis
    • Ascending aortic dilation- Unrelated to stenosis severity. Due to medial degeneration.
    • Aortic dissection- Risk is increased 5 to 9 times
• Calcific AS-
  • Also called senile or degenerative AS
  • Proliferative and inflammatory changes present. Not simple wear and tear.
  • Calcification of commissures causes AS.
  • Pathogenesis may be similar to atherosclerosis.
  • Risk factors for development- dyslipidemia, diabetes, hypertension, smoking
  • Higher prevalence in Paget disease and ESRD.
  • There may be coexisting mitral annular calcification.
  • Even if there is no AS, calcific aortic sclerosis increases cardiovascular death and MI by 50%
  • Rosuvastatin has been shown to decrease progression of less severe AS to severe AS.
• Rheumatic-
  • Commissural fusion and cusp stiffening. Central small opening. So usually AS + AR.

Pathophysiology

• Mechanisms of myocardial ischemia-

• Increased myocardial oxygen consumption due to-
  • Increased LV systolic pressure
  • Increased LV ejection time
  • LVH
• Decreased myocardial oxygen supply due to-
  • Increased LV diastolic pressure
  • Decreased diastolic time
  • Decreased aortic pressure

• Wall stress- There are two types of response. In one type, wall stress is not allowed to rise by development of concentric LVH- this is more likely in females. Males are more likely to have ventricular dilation, eccentric hypertrophy, rise in wall stress and systolic dysfunction.
• Diastolic dysfunction (rise in diastolic pressure) occurs due to myocardial hypertrophy and interstitial fibrosis.
• LV pressure tracing-
  • Increased systolic pressure
  • Rounded top (not normal flat top)
  • Increased end-diastolic pressure
• LA pressure tracing-
  • Large a waves
• Atrial contraction in AS- Very important booster pump function as it ensures filling of LV and prevents increase in LA pressure.
• PAH in AS-
  • Due to increased LV diastolic pressure
  • Mild PAH in one-third cases
  • Severe PAH in 15% cases
• Exercise in AS-
  • Cardiac output is normal at rest, but does not rise with exercise.

Symptoms

• Time of onset of symptoms-
  • BAV- 50 to 70 yrs
  • Calcific AS- > 70 yrs
• Exercise intolerance-
  • Most common initial presentation
  • Dyspnea or fatigue with exertion
  • Dyspnea with exertion is due to diastolic dysfunction
  • Fatigue with exertion is due to inadequate rise of cardiac output
• Angina-
  • Causes-
    • Mismatch in myocardial oxygen demand-supply ratio
    • Coexistent CAD- in half cases
    • Calcium embolism- very rare
  • Features- typical exertional angina
• Syncope (or presyncope)-
  • Causes-
    • Exertional syncope-
      • Systemic vasodilation with fixed cardiac output
      • Baroreceptor malfunction
      • Vasodepressor response to increased LV systolic pressure
    • Syncope at rest-
      • Transient VF
      • Transient AF
      • Transient AV block (calcium extending to conduction system)
• Heart failure-
  • Orthopnea, PND
  • Late feature
• GI bleeding
  • Angiodysplasia of right colon
  • Mechanisms- High shear stress causes
    • Platelet aggregation
    • Reduction in high molecular weight multimers of von Willebrand factor and
    • Increase in proteolytic subunits
• Infective endocarditis-
  • More in non-calcified AS than in calcified AS
• Embolism-
  • Sources-
    • Microthrombi from valve
    • Calcium

Physical examination-

• Pulse-
  • Parvus and tardus pulse-
    • Slow rising, late peaking, low amplitude
    • Specific for severe AS
  • Normal pulse- AR, HT
• BP-
  • Low systolic and pulse pressures
  • Normal- AR, inelastic arterial bed in elderly
• Carotid shudder-
  • Thrill in carotids due to radiation of AS murmur to carotids
• Heaving LV type apex
• Palpable and audible LV S4
• Systolic thrill in aortic area, suprasternal notch and carotids- specific for severe AS
• Mid systolic murmur-
  • Late peaking
  • Best in base of heart
  • Radiation to carotids
  • In calcific AS, high frequency components radiate to apex- Gallavardin phenomenon
  • Grade 3 or more intensity indicates severe AS- specific, but not sensitive
  • With LV failure, murmur intensity decreases and murmur may disappear.
  • Dynamic auscultation-
    • Increases after long pause in AF and after VPC- helps to differentiate from MR
    • Increased with squatting
    • Decreased with Valsalva
    • Decreased with standing
• S1- normal or soft
• LV S4
• S2-
  • Single S2 due to-
    • Prolonged LV ejection time or
    • Absent A2 due to immobility
  • Normally split S2 makes severe AS unlikely in older adults
  • Normally split S2 is possible in severe AS in young adults as valve mobility is preserved.
• Aortic ejection sound-
  • Due to halting of upward movement of aortic valve
  • Depends on valve mobility- heard in children and young adults with congenital AS; not heard in older adults with calcific AS

Echocardiography-

• Evaluation of AS severity may be inaccurate in-
  • HT- reevaluate after BP control
  • LV dysfunction- do dobutamine echo

ECG-

• LVH- correlation between QRS voltage and AS severity is good in children (not good in adults)
• LAE
• AF- in 10 to 15%
• AV conduction defects and IVCD- in 5% of calcific AS- due to extension of calcium to conduction system

Chest radiography-

• Rounding of apex due to concentric LVH
• Dilation of ascending aorta- more prominent if bicuspid aortic valve

Natural history-

• Asymptomatic AS- chance of symptoms at 2 years-
  • Mild AS- 16%
  • Severe AS- 79%
  • Asymptomatic severe AS -chance of sudden death- 1% per year
• Time of death with symptoms-
  • Angina- 5 yrs
  • Syncope- 3 yrs
  • Heart failure- 2 yrs
• Hemodynamic progression- annual change-
  • Valve area- 0.12 cm2
  • Peak velocity- 0.32 m/s
  • Mean gradient- 7 mmHg
• Rapid hemodynamic progression is seen with-
  • Severe calcification
  • Old age
  • Smoking
  • HT
  • Hyperlipidemia and
  • Renal insufficiency
• Evaluation of patients with absent or equivocal symptoms-
  • TMT- symptoms or BP fall (Note- avoid TMT in symptomatic patients)
  • BNP elevation

Management

Medical treatment

• Severe AS- avoid vigorous physical activity
• Diuretics decrease dyspnoea but may decrease cardiac output
• ACE inhibitors- give only if LV failure- use with caution
• Beta blockers- avoid- causes LV failure
• Vasodilators for other purposes like angina- be careful in titration as there will be no compensatory increase in cardiac output
• Atrial fibrillation- try to cardiovert

Surgical treatment

• Child, adolescent or young adult with congenital severe AS
  • Procedure-
    • First choice is balloon valvotomy
    • Second choice is surgical valvotomy
  • Indications- (any one of the following)
    • Symptoms
    • Gradient more than 60 mmHg
    • ST changes at rest or with exercise
• Adults with severe AS-
  • Procedure-
    • AVR (after coronary angiography)
    • Balloon valvotomy- if patient cannot tolerate surgery
    • Percutaneous aortic valve replacement if patient cannot tolerate surgery – not widely available
  • Indications- (any one of the following)
    • Class I-
      • Symptoms
      • EF less than 50%
      • Undergoing cardiac surgery including CABG
    • Class IIb-
      • TMT causes symptoms or BP fall
      • Rapid disease progression
      • Very severe AS, severe valve calcification
• AS with LV dysfunction
  • Surgical risk is high if EF is less than 35%
  • AVR should still be done as survival is improved
  • Nitroprusside is used as bridge to surgery
  • AVR may not be beneficial in advanced HF (high operative risk) and in patients with HF due to past MI (in whom AVR may not improve LV function)
• AS with low gradient and low cardiac output
  • DDs-
    • Severe AS with LV dysfunction
    • Mild AS with LV dysfunction due to dilated cardiomyopathy
  • Dobutamine stress echo-
    • Severe AS- Increase in gradient. No change in valve area.
    • Mild AS- Increase in valve area.
    • Also assesses contractile reserve- predicts improvement in LV function after surgery
• Results of AVR-
  • Operative mortality-
    • 4% (note- that of MVR is 6%)
    • 1% if age is less than 70 years
    • 7% if associated CABG
  • 10 year survival-
    • 85%
  • Higher surgical risk in-
    • Old age
    • Associated CAD
    • LV dysfunction
    • Females

• MS is rheumatic in 99% cases.
• Rheumatic heart disease-
  • Mitral – 65%
  • Aortic- 35%
  • Tricuspid- 6%
  • Pulmonary- rare
• RHD is multivalvular in 38% cases.
• Rheumatic mitral valve disease-
  • MS- 25%
  • MS + MR- 40%
• Aschoff nodules are present in myocardium.
• Fish mouth or button hole appearance
• Correlation between pathology and type of mitral valve disease
  • Commissural fusion with fish mouth appearance in diastole and closure during systole- MS
  • Fixed orifice- MS + MR
  • Chordal contraction without commissural fusion- MR without significant MS
• Causes of progression of rheumatic heart disease-
  • Recurrent rheumatic fever
  • Continuing autoimmune damage
  • Trauma due to blood turbulence causes damage
• Etiologies of MS-
  • Rheumatic
  • Congenital
  • Rheumatoid
  • SLE
  • Malignant carcinoid
  • Amyloidosis
  • Methysergide
  • Hurler-Hunter
  • Fabry disease
  • Whipple disease
  • Mitral annular calcification
  • Infective endocarditis (large vegetations causing obstruction)
• Conditions mimicking MS-
  • LA myxoma
  • Ball valve thrombus
  • Cor triatriatum

Pathophysiology

• Normal MVA is 4 to 6 cm2
• Tachycardia decreases diastolic LV filling time leading to increase in LA pressure.
• Hyperkinetic circulatory states increase flow rate across mitral valve leading to increased transmitral gradient leading to increased LA pressure. Note that gradient is proportional to square of flow rate.
• LV in MS-
  • LVEDV is reduced in 15% while it is normal in the rest
  • Failure of LVEDV and hence SV to increase with exercise
  • LV systolic function (LVEF etc) is reduced in 25% due to chronically reduced preload and increased afterload. It is normal in the rest.
  • RWMA of posterobasal segment due to extension of mitral valve scarring
  • LV diastolic dysfunction due to leftward shift of IVS
• At MVA of 1 cm2, 20 mmHg gradient is needed for mitral flow.
• Types of PAH in MS-
  • Passive
  • Reactive (due to PVH)
  • Obliterative
• Reactive PAH is said to be present when PA mean pressure – LA mean pressure is more than 10 mmHg.
• Effects of PAH in MS-
  • Right heart failure
  • Reduced cardiac output
  • Protection from pulmonary edema
• RV failure occurs at RVSP of 70 mmHg.
• Exercise hemodynamics in MS-
  • Moderate MS- spectrum-
    • One end- rise in cardiac output with rise in gradient- dyspnoea
    • Other end- inadequate rise in cardiac output with minimal rise in gradient- weakness
  • Severe MS-
    • Inadequate rise in cardiac output with rise in gradient- weakness with dyspnoea
• LA in MS-
  • Causes of LA disease-
    • Increased pressure
    • Rheumatic inflammation of LA wall
  • LA pathology-
    • Dilation
    • Fibrosis
    • Disorganization of muscle
    • Calcification
    • Thrombus
  • Effects of AF on LA-
    • Further LA enlargement
    • Atrial muscle atrophy
    • Inhomogeneity of atrial conduction and refractoriness.
    • Propensity to persistent AF
• Mitral stenosis grades (valve area in cm2)-
  • Very mild- 2.5 to 2.1
  • Mild – 2 to 1.6
  • Moderate- 1 to 1.5
  • Severe- less than 1
• Smallest MVA compatible with life is 0.3 cm2.

Symptoms

• Symptoms of MS-
  • Dyspnoea on exertion
  • Fatigue on exertion
  • Hemoptysis
  • Chest pain (15%)
  • Palpitations
  • Systemic embolism
  • Syncope
  • Hoarseness of voice
  • Right heart failure
• Causes of syncope in MS-
  • Ball valve thrombus
  • PAH
  • Arrhythmias
• Mitral facies is caused by dilated veins in cheeks.
• Causes of dyspnoea in MS-
  • PVH
  • Reduced pulmonary compliance leading to increased work of breathing
  • Reduced vital capacity- due to interstitial edema and engorged pulmonary vessels
• Features of dyspnoea in MS-
  • Dyspnoea on exertion
  • Orthopnoea
  • PND
• Causes of hemoptysis in MS-
  • Rupture of bronchial veins or of pulmonary vein-bronchial vein collaterals
  • Rupture of pulmonary capillaries during pulmonary edema
  • Pulmonary infarction
• Causes of chest pain in MS-
  • RVH
  • CAD
  • Coronary embolism
  • Idiopathic
• Causes of hoarseness in AF (Ortner syndrome)
  • LA dilation
  • PA dilation
  • Enlarged tracheobronchial lymph nodes

Physical examination

• Physical examination features of MS-
  • Features of right heart failure may be present (elevated JVP, edema, hepatomegaly, ascites)
  • Mitral facies- pink patches on cheeks
  • Pulse may be low volume
  • Pulse is irregular if in AF
  • JVP shows prominent a wave if PAH
  • JVP shows absent a wave if in AF
  • JVP is elevated if in right heart failure
  • Tapping S1 at apex if AML is pliable
  • Diastolic thrill at apex
  • Left parasternal heave if PAH
  • Palpable P2 if PAH
  • Loud S1 with prolonged Q-S1 interval
  • Loud P2 and narrow split of S2 if PAH
  • Absent LVS3 and LVS4
  • RVS4 if PAH and RVS3 if RV failure
  • OS
  • PES if PAH
  • MDM at apex
  • TR PSM and PR EDM (GSM) if PAH
• Causes of soft S1 in MS-
  • Severe calcification of leaflets
  • Severe thickening of leaflets
• In severe MS, Q-S1 is lesser compared to in mild MS due to higher left atrial v wave.
• Cause of OS- sudden tensing of leaflets on completion of opening excursion
• Causes of loud S1 in MS are-
  • Mitral valve closes at higher rate of rise of pressure in LV due to delayed mitral closure due to high LA pressure
  • Wide closing excursion of mitral valve
• A2-OS interval- 40 to 120 msec
• Causes of narrow A2-OS interval (< 80 ms)
  • Severe MS
  • Tachycardia
• Causes of wide A2-OS interval (>100ms)-
  • Mild MS
  • Bradycardia
  • Slow fall of LV diastolic pressure- LV systolic or diastolic dysfunction
  • Low LA pressure- large compliant LA
• Differentiation of A2-OS from A2-P2-
  • On standing, A2-P2 narrows while A2-OS narrows
  • On inspiration, triple sound occurs as A2-P2 and A2-OS both widen
  • OS occurs after P2
  • OS is loudest at apex while P2 is loudest at pulmonary area
• P2 may occur after OS if there is RBBB
• Absent OS means that the body of the leaflets is calcified (not tip alone)
• Cause of increased A2-OS interval on standing- decreased venous return leading to LA underfilling leading to lower LA pressure leading to delayed mitral opening
• Cause of decreased A2-OS interval during exercise- increased LA pressure leading to earlier mitral opening
• Well’s index-
  • Q-S1 interval minus A2-OS interval
  • Expressed in units of 0.01 seconds
  • More than 2 units indicates MVA less than 1.2 cm2
• MDM-
  • Low pitched
  • Rumbling
  • Intensity is not related to severity
  • Duration is related to severity- in mild MS there are separate mid diastolic and presystolic murmurs while in severe MS, the mid diastolic murmur is long and merges with the presystolic murmur to produce a holodiastolic murmur.
• Causes of absent MDM in MS-
  • Thick chest wall and emphysema
  • Low cardiac output
  • Marked RV enlargement with RV occupying the apex
• To increase intensity of MDM-
  • Left lateral position
  • Held expiration
  • Auscultate after walking (isotonic exercise)
  • Isometric exercise
  • Squatting
• EDM in an MS patient is more likely to be due to AR than PR.
• Causes of mitral MDM other than MS-
  • MR
  • LA myxoma
  • Ball valve thrombus
  • VSD, PDA
  • HCM

Echocardiography

• Echocardiographic features of MS-
  • Leaflet thickening
  • Chordal thickening and shortening
  • Commissural fusion
  • Calcification of leaflets and chordae
  • Diastolic doming- due to commissural fusion
• Wilkins score
  • 4 to 16
  • 4 points each for leaflet thickness, leaflet mobility, leaflet calcification and chordal involvement.
• TEE in MS-
  • To assess MR severity
  • To rule out LAA clot

Chest radiography-

• Chest radiography features of MS-
  • Mitral valve- calcification
  • Left atrium-
    • Enlargement- straightening of left heart border, bulge on left heart border, double shadow, bulge on right heart border, elevation of left bronchus causing widening of carinal angle, bulge in barium swallow
    • Calcification of left atrial wall
  • Pulmonary venous hypertension (prominent upper lobe veins- cephalization or whisker sign)
  • Pulmonary capillary hypertension
    • Kerly lines- A, B, C
    • Pulmonary edema
    • Pleural effusion, interlobar effusion
    • Pulmonary hemosiderosis, pulmonary ossification
  • Pulmonary arterial hypertension-
    • Dilated main, right and left pulmonary arteries
    • Pulmonary artery calcification
  • RV and RA enlargement, dilated SVC
• LA enlargement is more in MR than in MS. PA, RV and RA enlargement are more in MS than in MR.
• Kerly B lines-
  • Short horizontal lines
  • Costophrenic angles
  • LA pressure more than 20 mmHg
• Kerly A lines- Long dense lines running to hilum

ECG-

• LAE
• RVH (present in half with RVSP 70-100 and in all with RVSP > 100)
• Right axis deviation

Cardiac catheterization-

• Indications-
  • With BMV
  • Discrepancy between clinical and echo findings
• Calculations-
  • Mean gradient across mitral valve
  • Calculation of MVA using Gorlin formula
• Features of LA pressure tracing in MS-
  • Mean pressure is increased
  • Prominent a wave
  • Slow y descent

Natural history

• After rheumatic fever, it takes minimum 2 years to develop MS.
• In US and Europe, severe MS occurs in old age while in India, it occurs in young age and may occur even in children as young as 6 years old.
• Annual decrease of MVA- 0.09 cm2.
• Rapid progression of MS- annual decrease of MVA more than 0.1 cm2.
• 5 year survival in MS in presurgical era-
  • NYHA III- 62%
  • NYHA IV- 15%
• 5 year survival in symptomatic MS in surgical era, but without intervention- 44%
• 10 year survival according to NYHA class-
  • I- 85%
  • II- 50%
  • III- 20%
  • IV- very low

Complications-

Atrial fibrillation-

• Commonest complication of MS
• Prevalence of AF according to age-
  • Second decade- 10%
  • Third decade- 17%
  • Fourth decade- 45%
  • Fifth decade- 60%
  • Sixth decade and beyond- 80%
• Incidence of atrial fibrillation in MS roughly parallels the age of the patient.
• AF worsens symptoms of MS by-
  • Decreasing diastolic filling time- leads to increased LA pressure
  • Loss of atrial contribution to LV filling- leads to increased LA pressure
  • LA thrombus leading to systemic embolization
• Factors correlating with frequency of AF-
  • Age (strongest)
  • Severity of MS
  • LA diameter
  • LA pressure
• 5 year survival of AF-
  • Without MS- 85%
  • With MS- 64%
• AF causes decrease in cardiac output by 20% in MS.

Systemic embolism

• Causes-
  • LA thrombus
  • IE (rare)
• Factors predisposing to systemic embolism in MS-
  • AF (present in 80%)
  • Spontaneous echo contrast in LA
  • LA size
  • Age
  • Low cardiac output
• Clinical features-
  • Cerebral
  • Coronary- leads to chest pain
  • Renal- leads to HT
  • Ball valve or free floating thrombus- syncope in specific body position, variability in physical findings- urgent surgery needed.
• Incidence of systemic embolism in MS in age less than and more than 35 years is 5% and 11% respectively. That in MS + AF is 27% and 32% respectively.

Infective endocarditis-

• Less common compared to MR and aortic valve disease

Management-

Medical-

• Rheumatic fever prophylaxis
• IE prophylaxis is not needed
• Indications for anticoagulation in MS-
  • AF (persistent or paroxysmal)
  • Embolic events
  • LA thrombus
  • LA diameter > 55 mm
  • Spontaneous echo contrast
• Decrease sodium intake
• Diuretics
• Beta blockers or non DHP calcium channel blockers to reduce heart rate (even in sinus rhythm, more useful in AF)
• Digoxin if AF with right heart failure

Percutaneous valvulotomy-

• Indications for BMV- moderate or severe MS with-
  • Symptoms (NYHA II or more)
  • PA systolic pressure more than 50 mmHg at rest or more than 60 mmHg with exercise
  • New onset AF
• Contraindications for BMV-
  • Moderate or severe MR
  • Severe calcification
  • Severe subvalvular fibrosis
  • Thrombus in LA or LV
  • Recent embolism
  • Bleeding disorders
  • Interatrial septal thickness more than 3 mm (relative contraindication)
• Indications for BMV in mitral valve not ideal for BMV-
  • Patients at high risk for surgery due to comorbidities
  • Pregnancy
  • Women wanting to become pregnant
• Techniques of percutaneous mitral valvotomy-
  • IAS puncture- inoue balloon
  • IAS puncture- two balloon side-by-side
  • Retrograde- using balloon
  • Reusable metallic valvulotome
• Mechanisms of benefit with BMV-
  • Commissural separation
  • Fracture of nodular calcium
• Complications-
  • MR severe enough to need surgery- 2%
  • Mortality- 1 to 2%
  • Cardiac perforation- 1%
  • Cerebral embolism- 1%
• Factors predicting poor outcome with BMV-
  • Calcification, especially of commissures
  • Extensive subvalvular fibrosis
  • Wilkins score more than 8
• TEE should be done just before BMV
• Ben Farhat series-
  • 7 year follow-up
  • Follow-up results of BMV and OMV are equal and are better than those of CMV
  • Freedom from reintervention-
    • OMV- 93%
    • BMV- 90%
    • CMV- 50%
• Balloon size for BMV (in mm)- (height in cm/10) + 10
• Double balloon BMV was first done by Al Zaibag
• Need for MVR at 2 years after BMV-
  • 3% if score less than or equal to 8
  • 14% if score more than 8
• If score in 12 or more, BMV is done only if surgery is not possible
• BMV gives good result if score is 8 or less
• BMV should give MVA of more than 1.5 cm2 and gradient less than 7 mmHg.
• Compared to Inoue balloon, double balloon gives better immediate results. But there is no change in restenosis or survival.
• BMV is better than CMV because-
  • CMV- blades may not be in commissures
  • BMV- balloon applies uniform pressure

Surgery-

• Surgical options-
  • CMV
  • OMV
  • MVR
• Indications- When BMV is not possible due to moderate or severe MR, LA thrombus or leaflet calcification + any one of the following
  • Significant symptoms (NYHA III or IV)
  • Severe PAH
  • Recurrent embolism despite anticoagulation
• CMV-
  • First done by Bailley
  • Cannot be done with LA thrombus, calcification, severe subvalvular disease or moderate or severe MR
  • Transatrial or transventricular
• OMV-
  • Preferred to MVR
  • Commissures are incised
  • Concurrent annuloplasty can be done for MR
  • LA thrombus, if present, is removed
  • LA appendage is amputated
  • Calcium in leaflets can be removed
  • Fused chordae are separated
  • Maze procedure is done if needed
  • LA and LV pressures are measured off bypass- if unsatisfactory, MVR is done
  • Restenosis rate after valvotomy (any type)- 20% at 10 years
  • Causes of restenosis after valvotomy (any type)- trauma due to turbulent flow
• MVR-
  • Loss of annular-papillary muscle continuity can affect LV function
  • Done in cases in which even OMV is not possible
  • Maze procedure is done if needed
  • Operative mortality is 3 to 8%
  • Mechanical prosthesis if age is less than 65 years; bioprosthesis if age is more than 65 years.
  • Presence of AF favors mechanical prosthesis.

Congenital mitral stenosis-

• Typical type- short chordae- survival 6 months
• Supravalvular ring- survival 5 years
• Parachute mitral valve- survival 10 years
• Anomalous mitral arcade

Incidence

• More in males (3:1).
• Usually isolated anomaly.
• Less commonly associated with VSD, TOF, PDA and coarctation of aorta.

Embryology

• Abrikossoff’s theory- abnormal septation of conotruncus into aorta and pulmonary artery
• Hackensellner’s theory- persistence of pulmonary buds with involution of aortic buds so that pulmonary buds form the coronary arteries.

Pathology

• LCA arises from pulmonary artery, but then runs a normal course.
• RCA arises normally and runs normally.
• LCA is smaller than normal while RCA is larger than normal and gives collaterals to LCA in children.
• Anterolateral LV is scarred and thinned.

Hemodynamics

• Fetus- No problem as PA supports LCA.
• First stage (neonatal) – PA supports LCA in neonate.
• Second stage- After 2 months, PA is unable to support LCA. So myocardial ischemia and then infarction occurs. This causes heart failure and death in first year of life. This is the fate in 85% cases. 15% survive and go on to stage III.
• Third stage- Adequate collaterals from RCA support the LCA. So patients reach childhood. The problems that can occur in this stage are-
  • Inadequate coronary perfusion to LV leads to demand myocardial ischemia causing exertional angina, exertional dyspnoea, exertional syncope and rarely sudden death.
  • Inadequate coronary perfusion to LV can cause MI
  • Papillary muscle dysfunction can cause MR
• Causes of inadequate LV perfusion-
  • Less blood reaching LCA from RCA
  • Coronary steal as ALCAPA acts as an RCA to PA conduit
• VSD may cause PA to support the LCA. In these cases closure of the VSD without correction of ALCAPA can be catastrophic.
• The infarcted part of the LV may become aneurysmal.

Symptoms-

• Infant is asymptomatic for first 2 months.
• Then restless and crying on exertion occurs suggestive of exertional angina.
• Then features of heart failure occur due to MI. Most infants die (85%). Some (10%) improve and reach childhood. Few (5%) reach childhood without any symptom in infancy.
• Manifestations in childhood and adulthood are exertional angina, exertional dyspnoea, exertional syncope and rarely sudden death. MI can occur. MR can become symptomatic.

Signs-

• Infant- LV apex cardiomegaly, LV S3, hepatomegaly, MR murmur
• Children and adults- Continuous murmur louder in diastole in left upper sternal border, MR PSM.

ECG-

• Infant- Q, ST elevation and T inversion in I, aVL and v3 to v6.
• Adults- LVH, ischemic changes.

Radiography-

• Infant- LV type cardiomegaly with LAE and PVH.

Echocardiography-

• LCA originates from PA- seen in PSAX as originating from lateral part of MPA just distal to the pulmonary valve
• Retrograde flow from LCA to PA
• RCA has normal origin
• LV hypokinesia, LV dysfunction, LA dilation
• Sometimes, LV endocardial fibroelastosis

Cath study and angiography

• Mandatory before surgery
• Aortic root angiogram (or selective RCA injection in adult)- Only RCA seen originating from aorta. Blood goes from RCA to LCA and then into PA.

Management-

• Reimplantation of LCA into aorta
• Takeuchi repair- Intrapulmonary tunnel to connect LCA to aorta
• Surgery is needed even if found in an asymptomatic child/adult because otherwise life expectancy is reduced (4^th decade).

• Coronary artery draining to coronary vein, cardiac chamber, vena cava or pulmonary artery.

Pathology

• Coronary involved-
  • 60%- RCA
  • 40%- LCA
  • <5%- both
• Drainage to-
  • RV- 40%
  • RA- 25%
  • PA- 15%
  • LA- 5%
  • LV- 3%
  • Coronary sinus or SVC- rare
• Coronary artery is dilated and tortuous proximal to the fistula

Hemodynamics

• Coronary steal occurs as blood is stolen by the fistula as fistula is connected to a low pressure site.
• Fistula to RA behaves like pretricuspid left to right shunt. Fistula to RV behaves like posttricuspid left to right shunt. Fistula to LA behaves like MR. Fistula to LV behaves like AR.

Clinical features

• Symptoms after 20 years of age.
• Angina, dyspnoea, palpitations
• Features of chamber dilation if the fistula is large
• Continuous murmur-
  • At right sternal border if into RA, at left sternal border if into RV and at left upper sternal border if into PA.
  • Peaks in systole or diastole, not at S2.
• Coronary to LV fistula causes a diastolic murmur.

ECG-

• Depends upon which chambers are enlarged
• Evidence of myocardial ischemia may occur

Radiography-

• Depends upon which chambers are enlarged

Echocardiography-

• Proximal coronary is dilated
• Site of entry can be seen by color flow
• When fistula is into PA, it is just above the pulmonary valve

Cath study –

• Oxygen step up if drainage to right sided chambers

Angiocardiography-

• Coronary angiography shows the fistula

Complications-

• Myocardial infarction
• Heart failure
• Embolism
• Rupture
• Infective endocarditis

Management

• Closure is advised, even if the patient is asymptomatic, to prevent rupture and infective endocarditis
• Coil closure is an alternative to surgery. It is closed at entry to cardiac chamber to avoid coronary damage.