NATURAL HISTORY AND TREATMENT OF AORTIC STENOSIS

29/FEB/2016

AORTIC JET VELOCITY (m/sec)

MEAN GRADIENT (mm Hg)

VALVE AREA (cm2)

NORMAL <1.5 <5 3.0-4.0MILD 2.5-2.9 <20 >1.5MODERATE 3.0-3.9 20-39 1.0-1.5SEVERE >4.0 >40 <1.0CRITICAL/VERY SEVERE >5.0 >60 <0.75

Symptoms in patients with AS and normal left ventricular

systolic function rarely occur until the AS is severe.

Many patients do not develop symptoms until critical valve obstruction is present, while

others have symptoms when the stenosis is less severe,

particularly if there is coexisting aortic regurgitation or systemic

arterial hypertension

• In his 1958 Nathanson Lecture, Dr Paul Wood argued prophetically that “aortic stenosis is a simple mechanical fault which, if severe enough, imposes a heavy burden on the left ventricle and sooner or later overcomes it” .

• The burden of AS on the left ventricle remains true today, but what has changed is that AS management is no longer simple.

TODAY’S DISCUSSION

SYMPTOMATIC AS

ASYMPTOMATIC AS

PROGRESSION OF ASYMPTOMATIC AS

• The average rate of increase in the mean systolic pressure gradient is 4 to 7 mmHg per year, but some patients show an increase of as much as 15 to 19 mmHg per year.

• Valve area declines at an average rate of 0.1 cm 2 per year, but some patients have little or no progression and others progress more rapidly.

• Aortic jet velocity increases by an average of 0.3 m/sec per year, but this is also variable

• Patients with mild disease (ie, aortic jet velocity less than 3.0 m/sec) are unlikely to develop symptoms due to AS over the ensuing five years.

• A substantial number of patients with severe AS are not yet symptomatic but these patients have low event free survival rates (56 to 63 percent at two years and 25 to 33 percent at four to five years).

• Studies at three different sites illustrate the range of predictive factors and rates of progression:

The strongest predictor of progression to symptoms is DOPPLER AORTIC JET VELOCITY

SEVERITY OF AORTIC VALVE CALCIFICATION IS ANOTHER IMPORTANT DETERMINANT OF OUTCOME IN PATIENTS WITH SEVERE AS

MEDICAL UNIVERSITY OF VIENNA

MAYO CLINIC

Clinical Outcomes in Prospective Studies of Asymptomatic Aortic Stenosis in Adults

Clinical Outcomes in Prospective Studies of Asymptomatic Aortic Stenosis in Adults

Risk factors for progression• The rate of progression of the stenotic lesion and the time to onset of

symptoms varies significantly among patients. • Whether patients at high risk for rapid progression can be successfully

identified remains controversial .• Several prospective series have attempted to identify risk factors for

progression in asymptomatic patients (with symptomatic patients being treated surgically) .

• Among the factors that may be important are:• Aortic jet velocity and valve area• Degree of valve calcification• Response to exercise testing• Cause of aortic stenosis• Hypercholesterolemia• Renal insufficiency• Hypercalcemia• Old age• Male gender• Smoking

Risk stratification in a patient with asymptomatic severe AS

Abnormal exercise test Elevated BNP Moderate to severe valve calcification Very high aortic velocity (>5 or 5.5 m/sec) Rapid increase in aortic velocity Increased hypertrophic LV remodeling Myocardial fibrosis Pulmonary hypertension

ACC/AHA guidelines on the management of valvular heart disease concluded that valve replacement should not be routinely performed for isolated severe

AS in asymptomatic patients

Surgical versus medical therapy• Consideration of surgery in an asymptomatic patient with

severe AS requires an appreciation of the relative risks of surgical and medical therapy.

• The surgical mortality of aortic valve replacement varies widely.

• If it is not well under 2 to 3 percent, then the operative risk clearly exceeds the risk (less than 1 percent) of sudden death in an asymptomatic patient who does not undergo surgery.

• Furthermore, valve replacement does not abolish the risk of sudden death.

Surgical versus medical therapy• Insertion of a prosthetic heart valve is also associated

with appreciable morbidity. • Among the complications of prosthetic heart valves are

prosthesis dysfunction, paravalvular leak, thrombus formation, arterial embolism, endocarditis, and the problems associated with anticoagulation.

• The incidence of serious complications depends upon the type of valve and a number of clinical variables, but significant complications occur at a frequency of at least 3 percent per year, and death due directly to the valve occurs at the rate of approximately 1 percent per year.

Surgical versus medical therapy- CONCLUSIONS

OPERATIVE RISK OF AVRSUDDEN DEATH RISK NOT TOTALLY ABOLISHEDPROSTHETIC VALVE COMPLICATIONS• Thus, even if surgical mortality can be

minimized, the combined risk of valve replacement and the late complications of a prosthetic valve exceed the possibility of preventing sudden death in a truly asymptomatic patient.

Very severe AS (ASYMPTOMATIC)

Comparison of overall survival (A) and survival free ofcardiac death (B) between the early surgery (OP) and

conventionaltreatment (CONV) groups.

Possible role of exercise testing• Exercise tolerance testing has been proposed as a possible method of risk

stratification in patients with severe AS who are asymptomatic with routine activity .

• The ability of exercise testing to identify asymptomatic patients with severe AS who are likely to develop adverse events was assessed in a meta-analysis of data from seven studies with a total of 491 patients (mean age 50 to 66 years).

• An abnormal stress test result was defined as development of symptoms such as dyspnea, angina, syncope or near syncope during exercise; a decrease in blood pressure or a <20 mmHg increase in systolic blood pressure during exercise; <80 percent of normal exercise tolerance; OR ≥2 mm horizontal or downsloping ST segment depression during exercise.

• In patients with normal stress test results, no sudden deaths were observed after one year of follow-up. In patients with abnormal stress test results, 5 percent had sudden cardiac death.

• Adverse cardiac events were observed in 21 percent with normal stress test results and in 66 percent of those with abnormal stress test results.

• No complications from stress testing were observed.

Possible role of exercise testing• On the other hand, exercise parameters did not add

predictive value to a multivariate model in an earlier prospective study of 123 asymptomatic patients with mild to severe valvular AS in whom yearly echocardiography and exercise testing were performed for a mean of 2.5 years .

• Based upon the available evidence, we do not recommend routine exercise testing to estimate prognosis in asymptomatic patients with AS. However, observations made during exercise may be of some value in providing an exercise prescription in patients who might otherwise excessively limit their activity .

• It may also be helpful when the history is equivocal as to whether the patient does or does not have symptoms

Possible role of exercise testing

• ACC/AHA guidelines concluded that the evidence was less well established but that exercise testing may be considered in asymptomatic patients with AS to elicit exercise-induced symptoms or an abnormal blood pressure response .

• Exercise testing should not be performed in symptomatic patients.

Criteria for a positive exercise test in asymptomatic patients with aortic stenosis

Development of dyspnea, angina, or presyncope or syncope, which should lead to stopping of the test

A rise in systolic pressure during exercise of less than 20 mmHg; the test is stopped if the systolic pressure falls more than 10 mmHg with exercise

Inability to reach 80 percent of the predicted normal level of exercise tolerance

More than 2 mm horizontal or downsloping ST segment depression compared to baseline that cannot be attributed to other causes; the test is stopped if there is more than 5 mm ST segment depression

The development of complex ventricular arrhythmias, such as ventricular tachycardia or more than four ventricular premature beats in succession, which should lead to stopping of the test

Possible role of brain natriuretic peptide

1. Among patients with severe AS, plasma BNP and N-terminal pro-BNP concentrations are higher in symptomatic than asymptomatic patients ,

Gerber IL, Stewart RA, Legget ME, et al. Increased plasma natriuretic peptide levels reflect symptom onset in aortic stenosis. Circulation 2003; 107:1884.

• Levels come down after aortic valve replacement. Weber M, Arnold R, Rau M, et al. Relation of N-terminal pro B-type natriuretic peptide to progression of aortic valve disease. Eur

Heart J 2005; 26:1023.

• Among asymptomatic patients, higher values are

independently predictive of symptom-free survival Bergler-Klein J, Klaar U, Heger M, et al. Natriuretic peptides predict symptom-free survival and postoperative outcome in severe aortic stenosis. Circulation 2004; 109:2302.

TODAY’S DISCUSSION

SYMPTOMATIC AS

ASYMPTOMATIC AS

SYMPTOMATIC PATIENTS

• Once even mild symptoms are present, survival is poor unless outflow obstruction is relieved.

• Survival curves derived from older retrospective studies show that the interval from the onset of symptoms to the time of death is approximately 2 years in patients with heart failure, 3 years in those with syncope, and 5 years in those with angina.

• More recent series have confirmed this poor prognosis, with an average survival of only 1 to 3 years after symptom onset.

SYMPTOMATIC PATIENTS • Among symptomatic patients with severe AS, the outlook

is poorest when the left ventricle has failed and the cardiac output and transvalvular gradient both are low.

• The risk of sudden death is high with symptomatic severe AS, so these patients should be promptly referred for surgical intervention.

• In patients who do not undergo surgical intervention, recurrent hospitalizations for angina and decompensated heart failure are common, associated with significant consumption of health care resources

examples

In the PARTNER trial, 179 patients with AS with heart failure symptoms were assigned to the standard therapy arm . The majority of these patients received balloon aortic valvuloplasty (64 percent during the first 30 days and 20 percent later). The mortality rate at one year was 51 percent in this group.

GUIDELINES

SURGERY VERSUS TRANSCATHETER

Surgical risk calculation for valve surgeries• The 2008 Society of Thoracic Surgeons (STS) risk models for CABG, valve surgery, or both

were developed and validated based on data on 774,881 patients operated on during 2002 to 2006. The STS registry includes data from nearly 90 percent of cardiac surgery providers in the United States . The models provide estimates of risk of mortality as well as several nonfatal complications such as stroke, renal failure, and prolonged ventilation. A calculator is available online ( file://www.sts.org/quality-research-patient-safety/quality/risk-calculator-and-models/risk-calculator ).

• The first EuroSCORE model was developed based upon data from 1995 to stratify risk of in-hospital mortality . This model has been replaced by the 2011 EuroSCORE II model, which was developed based on data from 22,381 patients in 43 countries operated on during May to July 2010 . Overall mortality was 3.9 percent, which is lower than would have been predicted by old risk models (additive predicted 5.8 percent and logistic predicted 7.6 percent). A calculator for the EuroSCORE II is available online ( www.euroscore.org ).

• The Ambler risk model for aortic and/or mitral valve surgery with or without concomitant CABG was developed from data from the Society of Cardiothoracic Surgeons of Great Britain and Ireland on 32,839 patients who underwent surgery during 1995 to 2003 (file://www.ucl.ac.uk/statistics/research/riskmodel/index.html ). A calculator is available online ( www.ucl.ac.uk/stats/research/riskmodel ).

Certain limitations as they don’t includePorcelain aorta(calcified ascending

aorta)Severe MACSevere PAHFrailityNutritional status

These are independently associated with high surgical risk

ISSUES?

• ROLE OF BAV?• ROLE OF TAVI?• MANAGEMENT OF AS WITH LV

DYSFUNCTION?• AS WITH LOW GRADIENT AND LOW CARDIAC

OUTPUT?• MEDICAL MANAGEMENT?• ROLE OF STATINS?

ROLE OF BAV(Balloon Aortic Valvuloplasty)

• BAV for degenerative aortic stenosis was initially described in 1985.

• Degenerative AS is the most common reason for intervention and it appears to be associated with a chronic inflammatory process.

• Unlike rheumatic mitral stenosis, commissural fusion is not the predominant feature in most older adult patients with calcific AS, and the primary mechanism of the balloon action is fracture of the nodular calcium deposits, which improves leaflet mobility during left ventricular contraction.

• Problems with BAVRECOIL/RESTENOSISHIGH COMPLICATION RATETEMPORARY BENEFITMODEST SURVIVAL BENEFIT

UNFORTUNATELY THE BENEFIT IS NOT DURABLE

• Restenosis with loss of symptom benefit occurs in approximately 50% by 6 months and in most patients by 1 year.

• Early restenosis occurring within hours or days results from early recoil and may be related to the pathology of the valve components or inappropriate balloon diameter (due to size or insufficient inflation).

• When restenosis occurs after several months, the process may be multifactorial, including the original degenerative process and an altered healing process with fibrosis and ossification.

Balloon aortic valvuloplasty for transcatheter aortic valve implantation is performed under rapid ventricular pacing (A), which decreases the effective cardiac output by inducing ventricular tachycardia (B). The balloon catheter (C) must be sized to the aortic annulus to avoid severe aortic insufficiency. Doubling of the valve area or a decrease in the transvalvular gradient by more than 50% (D) is considered a successful result.

ComplicationsMansfield Scientific Aortic Valvuloplasty Registry 1986-1988 (N = 492)

Rouen Series 2002-2005 (N = 141)

Procedural death 2 (4.9%) 3 (2.1%)

Postprocedural death (<7 days) 12 (2.6%) 3 (2.1%)

Cerebral embolic events 11 (2.2%) 2 (1.4%)

Transient ischemic attacks 5 (1.1%) 0 (0%)

Ventricular perforation with tamponade

11 (2.2%) 0 (0%)

Severe aortic insufficiency 5 (1.1%) 2 (1.4%)

Vascular complications (surgical repair) 27 (5.5%) 0 (0%)

Nonfatal arrhythmias 5 (1.1%) 5 (3.5%)

Other: myocardial infarction, sepsis, renal failure

8 (1.6%) 1 (1%

American heart journal 2014

SUCCESSFUL BAV IN 80.8% INHOSPITAL MAJOR COMP 6.8%, DEATH IN 2.5%56% MORTALITY AFTER SINGLE BAV AT 1 YEARPATIENTS BRIDGED TO SAVR HAD THE BEST OUTCOME

Guidelines- NO CLASS 1 OR 11a INDICATIONS FOR BAV

MOST WOULD AGREE

• It may be used for patients who have symptomatic AS in need of emergent noncardiac surgery. The hemodynamic improvement of BAV is immediate, and it may decrease the risk of general anesthesia. In these situations, the BAV should be reserved for patients with severe AS who have the potential for hemodynamic compromise.

• It may be used to determine the contributing role of AS to dyspnea in patients with concomitant severe lung disease and to gauge potential improvement and risks of undergoing SAVR or TAVR.

• It may be used to assess the myocardial contractile reserve in patients with a low pressure gradient or low ejection fraction in whom associated cardiomyopathy is questionable. Patients with no demonstrated contractile reserve can have a perioperative mortality rate as high as 62%.The indication for SAVR or TAVR can be clarified 2 to 3 weeks after BAV if the left ventricular ejection markedly improves.

ROLE OF TAVIFIRST ACCOMPLISHED IN 2002

NOT EVERY HIGH-RISK PATIENT WITH SEVERE, SYMPTOMATIC AS NEEDS TO BE TREATED WITH

TAVRPatient Characteristics Associated With Poor Prognosis After TAVI

CURRENTLY 2 AORTIC VALVE SYSTEMS ARE WIDELY AVAILABLE

The SAPIEN valve (Edwards Lifesciences, Irvine, Calif) incorporates a balloon-expandable stainless steel stent frame within which are sewn bovine pericardial leaflets . synthetic fabric sealing cuff surrounds the inflow of the valve to prevent paravalvular leaks. This is the valve evaluated in the PARTNER trial,and it is currently approved for clinical use in the United States. Its successor, the SAPIEN XT valve, is constructed of a chromium alloy frame and has various minor improvements and one major advantage in that it is compatible with newer low-profile delivery catheters. The next-generation SAPIEN 3 valve is compatible with even lower-profile delivery systems and has various improvements that facilitate accurate positioning and improve paravalvular sealing

CURRENTLY 2 AORTIC VALVE SYSTEMS ARE WIDELY AVAILABLE

The CoreValve ReValving System (Medtronic, Inc., Minneapolis) incorporates a self-expanding nitinol alloy frame within which are sewn porcine pericardial leaflets. A pericardial sealing cuff surrounds the inflow of the valve

Study N Age (yr)

ES (%)

STS Score (%)

PS (%)

AVA Pre-P (cm2)

AVA Post-P (cm2)

Mean Gradient Pre-P (mm Hg)

Mean Gradient Post-P (mm Hg)

NYHA Class III/IV Pre-P (%)

NYHA Class III/IV at 1 Yr (%)

LVEF Pre-P (%)

LVEF Post-P (%)

Survival at 1 Yr (%)

PARTNER cohort B2010

358 83.1±8 26.4±17.2 11.6±6 96.6 0.6±0.

21.5±0.

544.5±1

5.7 11±6.9 92

16 54 57 69

PARTNER cohort A2010

699 83.6 29.3±16

11.8±3.3 90.2 0.7±0.

21.59±0

.442.7±1

4 10.2±4 93 12 52.5±13 56±10 75.8

SOURCE XT2015 2166 81.4±6 20.5±1

2 8.4 NR 0.7 1.8 47.6 10.8 76.9 12.3 NR NR NR

FRANCE 22015 2107 82.9±7 22.2±1

415.6±1

2 96.9 0.7±.2 NR 48.6±16 NR 75.5 10.5 53.8±1

4 NR 76

PARTNER 2

2015284 84±8.7 NR 103±5 96.3 0.6±0.

2 1.6 45.2±14 10 96.8 12 52±13 NR 77.5

Results of the inoperable arm• Patients randomized to TAVR had lower rates of all-cause

mortality (30.7% vs. 50.7%, P < .001), cardiovascular mortality (19.6% vs. 41.9%, P < .001), repeat hospitalization (22.3% vs. 44.1%, P< .001), and the composite end point of death or repeat hospitalization (42.5% vs.71.6%, P < .001).

• During up to 2 years of follow-up, there was no evidence of degeneration of the valvular prosthesis or restenosis.

• Heart failure symptoms were less severe in patients treated with TAVR. Patients treated with TAVR had a higher incidence of major vascular complications (16.2% vs 1.1%, P < .001), major bleeding (22.3% vs. 11.2%, P < .001), and major strokes (5.0% vs.1.1%, P = .06). In patients with severe AS who are not suitable candidates for SAVR, TAVR should be the standard of care.

Results for the high-risk operative cohort

• The all-cause mortality rate at 30 days was slightly lower with TAVR than SAVR (3.4% vs. 6.5%, P = .07) but was similar at 1 year (24.2% vs. 26.8%), 2 years (33.9% vs. 35%), and 3 years (44.2% vs. 44.8%).

• Although the rates of all neurologic events were higher after TAVR at 30 days and 1 year (5.5% vs. 2.4% and 8.3% vs. 4.3%, P < .05), rates of major strokes were not significantly different between TAVR and SAVR at 30 days (3.8% vs. 2.1%, P = .2) or at 1 year (5.1% vs. 2.4%, P = .07).

• There were other important differences in periprocedural risks between the two groups, with more major vascular complications 30 days after TAVR (11.0% vs. 3.2%, P < .001)

• More major bleeding (19.5% vs. 9.3%, P < .001) and new-onset atrial fibrillation were common(16.0% vs. 8.6%, P = .006) after SAVR.

• Marked improvement of symptoms was similar after TAVR and SAVR, and it was sustained at 3 years for both groups.

• From these results, TAVR emerged as a viable alternative to SAVR for high-risk patients. The choice is made by the interdisciplinary heart team.

Results for the high-risk operative cohort

Study Proc. MR (%)

30-Day MR (%)

Valve in Valve (%)

Conv. Open AVR (%)

AI >2+ (%)

Major CVA or TIA (%)

Major VC (%) MI (%) AKI (%)

PM (%)(PACEMAKER)

Major Bleeding (

PARTNER Cohort A 0.9 3.4 2 2.6 12.2 5.6 11 0 1.2 3.8 9.3

PARTNER Cohort B 1.1 5.0 1.7 0 12 5/0 16.2 0 1.1 3.4 16.

PROCEDURAL CHARACTERISTICS AND COMPLICATIONS

Durability

• Current transcatheter valves appear to be sufficiently durable to provide benefit in the mostly elderly patients with comorbid conditions who are currently considered candidates.

• Accelerated wear testing has demonstrated in vitro durability of longer than 10 years, but midterm structural valve failure has not been rare, although clinical follow-up remains limited beyond 3 to 5 years.

• Whether such durability is sufficient for younger patients with the potential for longevity remains to be determined.

• However, the feasibility of transcatheter valve-in-valve implants in failing surgical and transcatheter bioprosthetic prostheses has been demonstrated, and this strategy may be appealing when eventual transcatheter valve failure occurs

CONCLUSION• Surgical aortic valve replacement remains the

current standard of care for symptomatic aortic stenosis because of a large body of favorable experience .

• In the absence of long experience and additional randomized comparisons, current guidelines recommend TAVR only for patients in whom the risk for morbidity or mortality with surgery is high (STS SCORE>10%)

MANAGEMENT OF AS WITH LV DYSFUNCTION

• SURGICAL RISK IS HIGHER• OVERALL PROGNOSIS EXTREMELY POOR WITHOUT AVR• AVR LEADS TO SIGNIFICANT CLINICAL AND

FUNCTIONAL RECOVERY.

• AVR IS THE PREFERRED MODALITY OF TREATMENT• TAVI SEEMED BENEFICIAL IN SOME NONRANDOMIZED

STUDIES• RCTs ARE REQUIRED TO MAKE A CONCLUSION.

GUIDELINES

AORTIC STENOSIS WITH LOW GRADIENT AND LOW CARDIAC OUTPUT

• Patients with critical AS, severe LV dysfunction, and low cardiac output (and hence a low transvalvular pressure gradient) often create diagnostic dilemmas for the clinician because their clinical presentation and hemodynamic data may be indistinguishable from those of patients with a dilated cardiomyopathy and a calcified valve that is not stenotic.

• Low-flow, low-gradient AS is defined as a valve area of 1.0 cm2 or smaller, with an aortic velocity of less than 4.0 m/ sec or mean gradient of 40 mm Hg or less

• Most often, low-gradient low-flow AS occurs in patients with a low ejection fraction (<50%). In this situation, severe AS can be distinguished from moderate AS with primary LV dysfunction based on the changes in valve hemodynamics during transient increases in flow, usually by increasing cardiac output with dobutamine.

• Severe AS is present if there is an increase in aortic velocity to at least 4 m/sec at any flow rate, with a valve area that remains less than 1.0 cm2; AS is not severe if the valve area is more than 1.0 cm2

• Dobutamine echocardiography also provides evidence of myocardial contractile reserve (an increase in stroke volume or ejection fraction >20% from baseline), which is an important predictor of operative risk, improvement in LV function, and survival after AVR in these patients.

• However, even in patients with a lack of contractile reserve, AVR should be considered if the mean gradient is greater than 20 mm Hg, because survival after AVR is better (roughly 50% at 5 years) than with medical therapy.

A, Increase in cardiac output and in mean aortic valve gradient from 24 to 47 mm Hg. Aortic valve area (AVA) remained 0.8 cm2. This patient underwent successful valve replacement. B, Increase in cardiac output and minimal increase in mean pressure gradient from 17 to 20 mm Hg. The final calculated aortic valve area was 0.7 cm2. The patient was found to have only minimal AS at the time of surgery. C, No change in cardiac output, with decrease in mean pressure gradient from 37 to 26 mm Hg, occurred in response to dobutamine. The test was terminated because of hypotension. The patient was found to have severe AS at the time of surgery

Medical management of AS• Most important principle in management is patient education

regarding the disease course and typical symptoms.

• Patients with severe AS should be cautioned to avoid vigorous athletic sports and physical activity. Such restrictions do not apply to patients with mild obstruction.

• Although medical therapy has not been shown to affect

disease progression, adults with AS (as with any other adult) should be evaluated and treated for conventional coronary disease risk factors, in accordance with established guidelines.

Medical managementSymptomatic aortic stenosis (AS) is an indication for aortic valve replacement and medical therapy has limited utility in treating symptoms. However, medical management may be required in patients who are not candidates for surgery (either due to comorbid conditions or patient refusal to undergo valve replacement).

Frequency of echo in asymptomatic patients with normal LV function

Severity ECHO

MILD 3-5 yearly

MODERATE 1-2 yearly

SEVERE 0.5-1 yearly

• Although diuretics are beneficial when there is abnormal accumulation of fluid, they must be used with caution because hypovolemia may reduce the elevated LV end-diastolic pressure, lower cardiac output, and produce orthostatic hypotension.

• ACE inhibitors should be used with caution but are beneficial in treating patients with symptomatic LV systolic dysfunction who are not candidates for surgery and, in fact, have been shown in epidemiologic studies to improve outcomes in patients with AS

• They should be initiated at low doses and increased slowly to target doses, avoiding hypotension.

• Beta-adrenergic blocking agents can depress myocardial function and induce LV failure and generally should be avoided in patients with AS.

ATRIAL FIB• AF or atrial flutter occurs in less than 10% of patients with severe AS,

perhaps because of the late occurrence of left atrial enlargement in this condition.

• When such an arrhythmia is observed in a patient with AS, the possibility of associated mitral valvular disease should be considered.

• When AF occurs, the rapid ventricular rate may cause angina pectoris. • The loss of the atrial contribution to ventricular filling and a sudden fall

in cardiac output may cause serious hypotension. • Therefore AF should be treated promptly, usually with cardioversion. • New-onset AF in a previously asymptomatic patient with severe AS may

be a marker of impending symptom onset

NONCARDIAC SURGERY AND PREGNANCY

• Adults with asymptomatic severe AS can undergo noncardiac surgery and pregnancy, with careful hemodynamic monitoring and optimization of loading conditions.

• When stenosis is very severe, however, elective AVR before noncardiac surgery or a planned pregnancy may be considered.

ROLE OF STATINS?

• Although elevated serum lipids are associated with the presence of aortic valve disease, to date there is no convincing evidence that lipid-lowering therapy affects disease progression.

• No benefit was seen in a small prospective randomized trial of atorvastatin versus placebo, despite a significant lowering of serum LDL levels, in patients with relatively advanced calcific AS

The Simvastatin and Ezetimibe for Aortic Stenosis (SEAS) Trial and the Aortic Stenosis Progression Observation: Measuring Effects of Rosuvastatin (ASTRONOMER) Trial randomly assigned 1800 and 269 adults, respectively, with mild to moderate AS to intensive lipid-lowering therapy versus placebo.

These studies were adequately powered and showed no improvement in mortality, time to valve replacement, or rate of AS progression in the treatment versus placebo groups.

TAKE-HOME MESSAGES• Hemodynamic progression of AS is variable. The aortic valve area

declines at an average rate of 0.1 cm 2 per year but some patients have little or no progression and others progress more rapidly.

• Peak aortic velocity and/or rate of progression of peak aortic velocity is associated with risk of death or aortic valve replacement.

• Mortality in patients with AS dramatically increases after the development of the cardiac symptoms.

• Symptomatic aortic stenosis (AS) is an indication for aortic valve replacement and medical therapy has limited utility in treating symptoms.

• TAVI is a suitable alternative in elderly patients with high surgical risk

THANKYOU

RESULTS POST AVR• Symptoms of pulmonary congestion (exertional dyspnea) and of myocardial ischemia

(angina pectoris) are relieved in almost all patients, and most patients will exhibit an improvement in exercise tolerance, even if it was only mildly reduced before surgery.

• Hemodynamic results of AVR also are impressive; elevated end-diastolic and end-systolic volumes show significant reduction.

• Impaired ventricular performance returns to normal more frequently in patients with AS than in those with AR or MR.

• However, the finding that the strongest predictor of postoperative LV dysfunction is preoperative dysfunction suggests that patients should, if possible, be operated on before LV function becomes seriously impaired.

• The increased LV mass is reduced toward (but not to) normal within 18 months after AVR in patients with AS, with further reduction over the next several years.

• Coronary flow reserve and diastolic function also demonstrate considerable improvement after AVR. However, interstitial fibrosis regresses more slowly than myocyte hypertrophy, so that diastolic dysfunction may persist for years after successful valve replacement.

RESULTS POST AVR