NET ATRIOVENTRICULAR COMPLIANCE a PROMISING PARAMETER IN ASESING RHEUMATIC MITRAL STENOSIS

NET ATRIOVENTRICULAR COMPLIANCE: A PROMISING PARAMETER IN ASSESING RHEUMATIC MITRAL STENOSIS Abdullah Al – Shafi Majumder MBBS,MD,FACC,FRCP,FESC,FSCAI Director and Professor of Cardio

NET ATRIOVENTRICULAR COMPLIANCE:

A PROMISING PARAMETER IN ASSESING

RHEUMATIC MITRAL STENOSIS

Abdullah Al – Shafi Majumder

MBBS,MD,FACC,FRCP,FESC,FSCAI Director and Professor of Cardiology, NICVD, Dhaka

• These Echocardiographic clips belong to a 25 years old lady who presented with progressive exertional breathlessness for last 3years

• For last 3months, despite optimum medical management she was breathless even on minimum exertion (NYHA class IV)

Her MVA was 1 sq cm, mean trans mitral pressure gradient was 23 mmHg, PASP was

84 mm Hg, E wave down slope was 4 sq m ; her net atrioventricular compliance was 3 ml/mm Hg

Another patient

• A 28 years old male,

• Presented with breathlessness on moderate exertion (NYHA class II) for last 4 months

His MVA was 1 sq cm, mean trans mitral pressure gradient was 11 mmHg, PASP was 55

mm Hg, E wave down slope was 2.4 sq m ; his net atrioventricular compliance was 5.3 ml/mm Hg

Comparison of 1st & 2nd patient

Comparison 1 st patient 2 nd patient

3 days after PTMC of the 1st patient

• She walked from ground floor to 3rd floor without any assistance & without feeling any shortness of breath

• Echocardiography 3 days after PTMC revealed…

Her MVA was 1.8 sq cm, mean trans mitral pressure gradient was 6 mmHg, PASP was 51 mm Hg, E wave down slope was 4.5 sq m : her net atrioventricular compliance was 5 ml/mm Hg

3 days after PTMC of the 2nd patient

• He walked from ground floor to 3rd floor without any assistance & without feeling any shortness

of breath

• Echocardiography 3 days after PTMC revealed…

His MVA was 1.7 sq cm, mean trans mitral pressure gradient was 4 mmHg, PASP was

26 mm Hg, E wave down slope was 1.9 sq m : his net atrioventricular compliance was 11.4 ml/mm Hg

Comparison of 1st & 2nd patient

following PTMC Comparison 1 st patient 2 nd patient

Comparison of 1st & 2nd patient

following PTMC Comparison 1 st patient 2 nd patient

BACKGROUND

In patients with mitral stenosis, the occurrence of

 Pulmonary arterial hypertension,

 Symptoms, and

 Adverse outcomes

do not always correlate with the classic markers of hemodynamic severity, particularly with

 Valve effective orifice area (EOA) and

 Transvalvular pressure gradients

Cardiologists are trying to detect the key parameter, assessment of which will be beneficial for the patients in terms of

 Accurate stratification of disease severity,

 Patient selection for intervention,

 Guidance of timing for intervention and

 Prognosis prediction

BACKGROUND

• Net atrioventricular compliance (Cn) is a relatively new parameter in the assessment of rheumatic MS patients

• Number of studies has been conducted to decide how far Cn correlates with PA pressure estimated by Doppler echocardiography in patients with moderate

to severe MS

• We shall discuss some of the basic aspects of Cn and its implications in the management of rheumatic mitral stenosis

BACKGROUND

Rheumatic mitral valvular

Rheumatic mitral valvular

• A community based study showed the prevalence of

rheumatic heart disease is 1.3 per 1000 in rural Bangladesh Tropical Doctor,2005, 35, pp 160-161

Rheumatic mitral valvular

heart disease

• Mitral stenosis (MS) is the commonest (54%) of all rheumatic heart diseases

1984 Rheumatic heart diseases in Bangladesh and Japan, JICA, Dhaka, pp 1-9

• Recent data shows almost same prevalence of MS among Rheumatic heart diseases

2013, Patients register, NICVD, Dhaka

Rheumatic mitral valvular

heart disease

• In the setting of mitral stenosis, increased transmitral gradient results in an elevation of left atrial pressure and then its backward transmission predisposes patients to pulmonary venous and finally pulmonary arterial hypertension, which is known to be the main mechanism for exercise intolerance and the development of dyspnea

Circulation 2000;102:2378-84

• A wide spectrum of LA pressures exists in patients with mitral stenosis despite nearly similar mitral valve area

• A linear relationship does not exist between the left atrial pressure and valve orifice or between left atrial pressure and pulmonary artery pressure

• It is due to the complex interactions between mitral orifice

area, left atrial compliance and pulmonary compliance

American Heart Journal.1977; 94: 73-80

Rheumatic mitral valvular heart disease

Rheumatic mitral valvular heart disease

• MS is best described as a disease continuum, with no single value that can define its severity

• More specifically, a wide variation in pulmonary pressures for the same range of mitral obstruction emphasizes the need to identify key factors implicated in the development of

pulmonary hypertension and functional limitation in MS

Am J Cardiol 1996;78:1060–1062

Concept of Compliance

• The term compliance is used to describe how easily a chamber of the heart or the lumen of a blood vessel expands when it is filled with a volume of blood

• Physically, compliance (C) is defined as the change in volume (ΔV) divided by the change in pressure (ΔP)

• C = ΔV / ΔP (Richard E Klabunde, 2011)

Ventricular Compliance

As the ventricle fills with blood, the pressure and volume that result from

filling are determined by the compliance of the ventricle

Normally, compliance curves are plotted as the change in volume (ΔV)

over the change in pressure (ΔP) For the ventricle, however, it is common

to plot ΔP versus ΔV Therefore, the slope of the relationship is the reciprocal of the compliance, which is sometimes referred to as ventricular "stiffness."

• The compliance of the ventricular is determined by the

 Physical properties of the cardiac muscle and

 Other tissues making up the ventricular wall as well as

 By the state of ventricular contraction and relaxation

Conception of Compliance

• For example, in ventricular hypertrophy the ventricular compliance is decreased (i.e., the ventricle is "stiffer"), therefore,

 Ventricular end-diastolic pressure (EDP) is higher at any given end-diastolic volume (EDV)

 Alternatively, at a given EDP, a less compliant ventricle would have a smaller EDV (i.e., filling will be impaired)

Concept of Compliance

• If ventricular relaxation is impaired (as occurs in some forms of heart failure), the functional ventricular compliance is also reduced (because of residual active tension), which will also impair ventricular filling

Concept of Compliance

• In a disease state such as dilated cardiomyopathy, the ventricle becomes very dilated without appreciable thickening of the wall

• This dilated ventricle will have increased compliance; therefore, although the EDV may be very high, the EDP may not be greatly elevated

Concept of Compliance

Net atrioventricular compliance (Cn)

• In case of pure mitral stenosis, left ventricular compliance is assumed to be normal

• Therefore an abnormal Cn reflects abnormality of the left atrial compliance

• But it has been found that about one third of patients with mitral stenosis have reduced left ventricular compliance

Circulation 1992; 85: 1447-1456

Net atrioventricular compliance (Cn)

• The net atrioventricular compliance (Cn) implies compliance characteristics of both the chambers atrium and ventricle, as a single unit

• Net atrioventricular compliance (Cn) is an important determinant of pulmonary artery pressure in mitral stenosis independently of mitral valve (MV) area and transvalvular pressure gradients

• Patients with low Cn were more symptomatic with symptoms corresponding to severe increases in pulmonary artery

pressures during stress echocardiography

Ehud Schwammenthal et al (2000)

Net atrioventricular compliance (Cn)

• The cardiac stroke volume can be calculated using the Fick method

• Similarly, mean left ventricular compliance (Cv) can

be estimated as the stroke volume divided by the diastolic rise in left ventricular pressure

• Ventricular compliance can be calculated using a left ventricular catheter passed retrograde through the aortic valve Fluid-filled catheters are used to measure the pressures

• Cn will then be calculated as (1/Ca+1/Cv) -1

Methods of measuring Cn

Methods of measuring Cn

• Cn can be readily calculated by Doppler echocardiography

• Cn was originally used for analysis of transmitral flow

by Thomas and Weyman, demonstrating that the pressure halftime to estimate MV area varies inversely with orifice area but also directly with net left atrial and ventricular compliance and the square root of the peak transmitral gradient

Methods of measuring Cn

• Flachskampf et al presented analytic and numeric evidence supporting the quantitative assessment of Cn from transmitral velocity profiles, deriving a simple equation that relates it to effective MV area and E-wave downslope

• Schwammenthal et al showed that Cn can be calculated noninvasively and reproducibly in the clinical setting and correlates well with invasively determined values

MVA s 1.7 sq cm, E wave down slope was 1.9 sq m

So his net atrioventricular compliance is 11.4 ml/mm Hg

Prognostic significance

• Although Cn seemed to be an important determinant of cardiovascular performance in MS, few data were available on its prognostic implications

• The 1 st study that evaluated the relation between Cn and clinical events was limited by the small number of patients enrolled and by an assumed cutoff value for Cn The authors acknowledged the need for further prospective studies in more patients and the limitation of an

assumed cutoff used for Cn in that analysis

J Am Soc Echocardiogr 2008;21:482–486

Maria Carmo P Nunes et al (2013) showed that net atrioventricular compliance,Cn ≤4 mL/mm Hg best predicted unfavorable outcome in patients with mitral stenosis

Prognostic significance

• In that study ,Cn was found adding prognostic information beyond that provided by clinical evaluation and MV area

Prognostic significance

• Importantly, baseline Cn might provide its greatest value by predicting a progressive course with subsequent need for intervention in initially asymptomatic patients

• The authors concluded that Cn assessment therefore had potential value for clinical risk stratification and monitoring in MS patients

Intervention-free survival curves for patients stratified by net atrioventricular compliance (Cn) ≤4

mL/mm Hg compared with patients with Cn >4 mL/mm Hg (log rank,

30.5; P<0.001)

Intervention-free survival curves for patients with moderate-to-severe anatomic mitral stenosis without indication for mitral valve intervention at baseline.The event-free survival rate was significantly higher in the patients with net atrioventricular compliance (Cn) >4 mL/mm Hg than in

those with Cn ≤4 mL/mm Hg (log-rank, 15; P<0.001)

Scatterplot showing correlation between systolic pulmonary artery pressure (SPAP) and net stiffness (1/net atrioventricular compliance [Cn]) There is a nonlinear negative relationship between Cn and SPAP and a positive correlation with stiffnes

Prognostic significance

• In another study Maria Carmo P Nunes et al (2013) showed that Cn is an independent predictor of death in patients with significant MS, even after adjustment for important prognostic factors

• The authors concluded that Cn reflected the overall hemodynamic consequence of the mitral valve obstruction, and should be considered in evaluating mortality risk in this setting

JACC March 12, 2013 Volume 61, Issue 10.

Promising aspects of Cn in management of MS, where further researches are required

• Detection of time of intervention:

Cn can predict the outcome of patients with MS, but still today the timing of intervention is dictated by patient’s symptoms, MVA, transvalvular pressure gradient, PASP etc

Promising aspects of Cn in management of MS…

• Helping in choice of patient for intervention:

 Where there is discrepancies between symptoms and conventional echocardiographic parameters, requiring more complete evaluation of physiology

 Baseline Cn may have its greatest use in this subset of patients

by providing an additional indication of impaired physiology and progression to the need for intervention

Promising aspects of Cn in management of MS…

• Relation with impairment of RV function:

• The pathophysiological mechanisms of RV dysfunction in MS are unclear

• RV dysfunction is not a simple expression of elevated pulmonary artery pressure.

• Pande et al (2009) showed that RV dysfunction was observed in all cases

of rheumatic MS regardless of PASP

• Sagie et al (1996) demonstrated that right heart disease can progress independently of MV area

• Maria Carmo P Nunes et al (2013) showed that, echocardiographic indices

of RV function weakly correlated with SPAP and had no independent effect

on the clinical outcome

• In fact, normal RV function does not reliably exclude significant pulmonary hypertension in MS

• So a relation of decline Cn with RV function impairment in MS patient is not yet established and further studies are required to evaluate relation between RV function, PASP, Cn, MVA & transvalvular pressure gradient

Promising aspects of Cn in management of MS…

• Improvement of Cn following MV intervention is

not yet established

 Aditya Kapoor et al (2004) found that left atrial compliance significantly improved immediately after successful balloon mitral valvotomy, irrespective of the pre valvotomy left atrial

pressure

 The effect of a successful PTMC or MVR on Cn is still not evaluated

 If improvement occurs, whether this improvement is related

to mortality or morbidity benefit is also not clear

Promising aspects of Cn in management of MS…

 An observational study titled “ Assessment of net

atrioventricular compliance in patients undergoing PTMC” is going on in National Institute of Cardiovascular Diseases, Bangladesh

 We are expecting the result by the middle of next

year

• Relation of Cn with patients age, disease duration &

inflammatory markers is not yet determined

Promising aspects of Cn in management of MS…

Limitation of Cn as a

parameter

• Normal reference value is not available

• What’s the impact of age, sex, ethnicity & other demographic variable on Cn in not known

• The absolute value of Cn, to what extent it is significant is questionable