Congenital valvular aortic stenosis in young adults: Predictors for rate of progression of stenosis and aortic dilatation

Background

Congenital aortic stenosis (AS) is the most common obstructive left-sided cardiac lesion in young adults, however little is known about the progression in adults. Therefore, we aimed to evaluate the progression rate of AS and aortic dilatation in a large multicenter retrospective cohort of asymptomatic young adults with congenital valvular AS.

Methods

Data were obtained from chart abstraction. Linear mixed-effects models were used to evaluate the progression of AS and aortic dilatation over time. A joint model combining longitudinal echocardiographic and survival data was used for survival analysis.

Results

A total of 414 patients (age 29 ± 10 years, 68% male) were included. Median follow-up duration was 4.1 (2.5–5.1) years (1587 patient-years). Peak aortic velocity was 3.4 ± 0.7 m/s at baseline and did not change over time in the total patient population (− 0.01 ± 0.03 m/s/year). Increased left ventricular mass was significantly associated with faster AS progression (p < 0.001). Aortic dilatation was present in 34% at baseline and 48% at follow-up (p < 0.001). The aortic diameter linearly increased over time with a rate of 0.7 ± 0.2 mm/year. Rate of aortic dissection was 0.06% per patient-year. Seventy patients required an aortic valve intervention (4.4% per patient-year), with AS progression rate as most powerful predictor (HR 5.11 (95% CI 3.47–7.53)).

Conclusions

In the majority of patients with mild-to-moderate congenital AS, AS severity does not progress over time. However patients with left ventricular hypertrophy are at risk for faster progression and should be monitored carefully. Although aortic dissections rarely occur, aortic dilatation is common and steadily progresses over time, warranting serial aortic imaging.     

Syndrome of valvular pulmonary stenosis and valvular aortic stenosis with atrial septal defect

Clinical and morphological findings are described in 2 adults with combined valvular pulmonary and aortic stenosis with atrial septal defect, an extremely rare combination of lesions. The direction of the shunt via the atrial septal defect in this combination appears to be dependent on the relative degree of outflow obstruction on the right side compared with the left side of the heart. In 1 patient the degree of obstruction at the pulmonary valve was nearly three times that at the aortic valve and, therefore, the shunt was right to left and the patient was severely cyanotic. In the other patient, the degree of obstruction at the pulmonary valve was slightly less than that at the aortic valve and, therefore, the shunt was entirely left to right and the patient was acyanotic. Diagnosis of an associated obstructive lesion on the left side of the heart in a patient with an obstructive lesion on the right side of the heart is essential because operative relief of the right-sided obstruction without relief of the left-sided obstruction may lead to rapid, fatal pulmonary congestion.     

Syndrome of valvular pulmonary stenosis and valvular aortic stenosis with atrial septal defect.

Clinical and morphological findings are described in 2 adults with combined valvular pulmonary and aortic stenosis with atrial septal defect, an extremely rare combination of lesions. The direction of the shunt via the atrial septal defect in this combination appears to be dependent on the relative degree of outflow obstruction on the right side compared with the left side of the heart. In 1 patient the degree of obstruction at the pulmonary valve was nearly three times that at the aortic valve and, therefore, the shunt was right to left and the patient was severely cyanotic. In the other patient, the degree of obstruction at the pulmonary valve was slightly less than that at the aortic valve and, therefore, the shunt was entirely left to right and the patient was acyanotic. Diagnosis of an associated obstructive lesion on the left side of the heart in a patient with an obstructive lesion on the right side of the heart is essential because operative relief of the right-sided obstruction without relief of the left-sided obstruction may lead to rapid, fatal pulmonary congestion.     

Unnecessary deaths from valvular aortic stenosis

The annual mortality from aortic valvular stenosis was calculated among potential candidates for surgical replacement of the aortic valve. From the Swedish Central Register of Causes of Death, 70 patients below the age of 80 years who had died from aortic stenosis during a 1-year period in the County of Stockholm (population 1.5 million), were identified. A retrospective analysis of their medical records showed that 37 individuals were suitable candidates for surgery. The presence of aortic stenosis had been verified at autopsy in 31 (84%) patients. The remaining six patients (16%) had their aortic stenosis diagnosis established by a thorough non-invasive investigation performed before death. Although typical signs and symptoms of aortic stenosis were recorded in all 37 patients, only six (16%) of them had been considered by their physicians to be suitable candidates for surgery prior to death. The deceased patients were compared with a group of 68 patients who had undergone aortic valve replacement for aortic stenosis during the same period. There were no significant differences between the two groups with regard to symptoms and clinical findings, except for a higher incidence of syncope in the operated group. It is concluded that, of 105 (68 surgically treated and 37 deceased) eligible patients with aortic stenosis, 37 individuals did not receive surgical care in time. The reason for this was probably insufficient knowledge of the curability of the disease.     

Combined hyertrophic subaortic stenosis and calcific aortic valvular stenosis.

A well documented case of combined hypertrophic subaortic stenosis and calcific aortic stenosis is reported. Detection of multilevel involvement in cases of left ventricular outflow obstruction requires a high index of suspicion and precise hemodynamic and angiographic documentation. Careful analysis of the total data base is necessary for proper management of the patient. The pathogenesis of this combined lesion is unclear: Asymmetrical septal hypertrophy may occur as a consequence of the valvular stenosis, or it may be that abnormal leaflet motion in patients with hypertrophic obstruction produces leaflet thickening, calcification, deformity and stenosis.     

Hemodynamic progression of adult valvular aortic stenosis

Hemodynamic progression of valvular aortic stenosis was studied in 54 patients who had serial cardiac catheterizations. There were 47 men and 7 women with a mean age of 61.2 years. The time interval between studies was 4.4 years (range, 0.4-12.2). Associated coronary artery disease was present in 37 patients (69%). The initial mean aortic valve area (Hakki's formula) was 1.26 cm2 (range, 0.66-2.85), and the aortic valve area at last follow-up was 0.77 cm2 (range, 0.29-1.95), with mean reduction of 0.49 cm2. The mean peak systolic gradient increased from 23.3 +/- 15.1 mm Hg at initial study to 52.6 +/- 27.5 mm Hg at last study, a mean increase of 29.3 +/- 23.6 mm Hg. Patients with no or mild left ventricular impairment and no or mild coronary artery disease are more likely to have progression than patients with more severe left ventricular impairment or coronary artery disease (P less than 0.05). Aortic valve replacement for progressive aortic stenosis was required at a later date after coronary artery bypass grafting in a small group of nine patients. In this small group, there was high intraoperative mortality of 33%.     

Mechanism of nitroglycerin effect in valvular aortic stenosis

The hemodynamic effects of nitroglycerin taken sublingually were studied during cardiac catheterization in 10 patients with valvular aortic stenosis. Hemodynamics and cineangiographic left ventricular volumes were determined before administration of nitroglycerin and at peak nitroglycerin effect. Diastolic pressure-time and ejection pressure-time product were used to evaluate left ventricular energy supply and demand. Pressurevolume loops and left ventricular wall tension were calculated. There was a decrease (P < 0.05) in aortic systolic pressure, but heart rate and aortic diastolic pressure did not change significantly. Left ventricular ejection pressure-time declined by more than 20 percent and diastolic pressuretime did not show a significant change. Thus, the ratio of diastolic pressure-time to ejection pressure-time increased from 0.59 ± 0.07 (mean ± standard error) to 0.71 ± 0.09 (P < 0.05). There were significant declines in left ventricular peak systolic and end-diastolic pressures, endsystolic and end-diastolic volumes and peak left ventricular wall tension. Thus, the peripheral unloading effects of nitroglycerin were reflected in the left ventricle despite the fixed aortic valve obstruction. There was no significant change in any measure of left ventricular contractility after administration of nitroglycerin.

It is concluded that sublingual nitroglycerin in aortic valve stenosis: (1) improves indirect indexes of left ventricular energy supply/demand ratio, (2) decreases left ventricular preload and afterload, and (3) does not change left ventricular contractility.     

Pathophysiology of valvular aortic stenosis in the elderly

Aortic stenosis in the elderly is related to calcification of either a bicuspid valve or a morphologically normal tricuspid valve. There is increasing evidence that factors relating to atherosclerosis are involved in valvular calcification and that it is an actively regulated process rather than a degenerative one. With severe aortic stenosis left ventricular hypertrophy occurs, decreasing wall stress and supporting the left ventricular ejection fraction. However, with pathologic hypertrophy there is a dropout of myocardial cells, subendocardial ischemia, and fibrosis. Eventually, symptoms of angina, non-Q wave myocardial infarction, exertional syncope, and heart failure occur. Once symptoms begin, the prognosis is poor, with sudden death occurring in about one third of patients who die. In the elderly, symptoms can be recognized very late in the course of the disease since they can be attributed to other problems and since the elderly patient may have reduced physical activity to a minimum. The more comorbidities that exist, the greater the risk of valve replacement. Symptomatic patients with severe aortic stenosis even over age 80 can be operated upon with a relatively low mortality and morbidity. In patients over age 80, prolongation of life for any meaningful length of time is not as important as relief of symptoms and improvement in the quality of life. Thus, it is unlikely that any truly asymptomatic patient over age 80, even with severe aortic stenosis, should be sent to surgery.     

Supravalvular and valvular aortic stenosis in homozygous familial hypercholesterolemia

Premature atherosclerosis with a particular predilection to the coronary arteries is a well-known complication of homozygous familial hypercholesterolemia. However, well documented involvement of the aortic root and valve with aortic stenosis has not been recognized frequently antemortem. Clinical, echocardiographic, hemodynamic and angiographic features of a case with valvular and supravalvular aortic stenosis secondary to homozygous familial hypercholesterolemia are described. Surgical relief of the left ventricular outflow obstruction was not attempted because of the patient's refusal.