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Autophagy as mechanism for cell death in degenerative aortic valve disease.

Once degenerative aortic valve disease becomes symptomatic, valve replacement is necessary for prognostic and symptomatic reasons. In elderly patients, symptoms of degenerative aortic valve can often be doubtful. Therefore, it is difficult but important to distinguish patients who need surgery from those who do not. Estimation of the rate of the progression of this disease can be helpful herein because one needs to bear in mind that aortic valve degeneration is an active process, which can influence the rate of progression. Recently, autophagy was discovered as a mechanism of cell death in different cardiovascular diseases such as atherosclerosis, aortic valve degeneration, heart failure and at regions around heart infarctions. Thus understanding autophagy in all its details can be helpful to contribute insights into the cell death machinery of cardiovascular diseases. This could open ways for inhibition of cell death in cardiovascular disease and possibly define targets for future drug design.

Aortic Valve↗

Calcific aortic valve disease should not be considered as a degenerative disease anymore.

Calcific aortic valve disease is common among the elderly. Until recently, the concept that calcific aortic valve disease is a degenerative and unmodifiable process basically induced by long-lasting mechanical stress was generally accepted. However calcific aortic valve disease is not merely related to age-associated "wear and tear". The development and progression of calcific aortic valve disease are based on an active process that shares a number of similarities with atherosclerosis. Statins and angiotensin-converting enzyme inhibitors have been shown to slow calcium accumulation in aortic valves. Thus, calcific aortic valve disease should not be considered as a degenerative disease anymore.

Aged↗

Aortic valve disease.

Management of aortic valve disease follows traditional algorithms: initial gross diagnosis, noninvasive imaging and quantitation, possible catheterization or angiography, and medical treatment until symptoms of prognosis prediction indicates surgery. Most advances in this subject reflect improved technology and additional data collection therefrom, and subsequent analysis. Noninvasive imaging, especially Doppler echocardiography and nuclear magnetic resonance imaging, enjoy continued refinement. Diastolic dysfunction, a particular pathophysiologic feature of aortic valve disease, has become more clearly characterized. New data reaffirm the old truth that heart failure in infective endocarditis foretells the need for surgery. Though we know more about aortic balloon valvotomy, it is only a temporary treatment. Surgeons still seek the perfect valve prosthesis. Lastly, technology has not lessened the high incidence of rheumatic heart disease in impoverished countries.

Aortic Valve↗

Association of Paget's disease of bone with calcific aortic valve disease.

To test the hypothesis that Paget's disease of bone is associated with a greater incidence of calcific aortic valve disease, a computer-generated list was obtained of all autopsy subjects from the Johns Hopkins Hospital in whom Paget's disease was diagnosed (n = 92). The severity of Paget's disease and cardiac valvular lesions was graded on a scale of 0 to 3, with 3 as the most severe. Two control cases were obtained for each case of Paget's disease. Each was the case either immediately before or after the Paget's case, and was matched for age, race, sex, and extent of autopsy. The incidences of moderate (10.9 percent) and severe (5.4 percent) calcific aortic valve disease were both fourfold greater than in the control group (chi-square analysis, p less than 0.01 and p less than 0.05, respectively). Additionally, the frequency of advancing grades of calcific aortic valve disease was greater in more advanced stages of Paget's disease. In fact, there was a dose-response effect of Paget's disease upon calcific aortic valve disease (trend analysis for proportion, p less than 0.01). These data therefore support the hypothesis that Paget's disease is associated with calcific aortic valve disease in a dose-response manner.

Aged↗

Coronary reserve in patients with aortic valve disease before and after successful aortic valve replacement.

In patients with aortic valve disease and normal coronary angiograms coronary reserve was determined by the coronary sinus thermodilution technique. Three groups of patients were studied: 37 preoperative patients; 18 different patients 12-52 months after aortic valve replacement and seven control subjects with no cardiac disease. Coronary flow ratio (dipyridamole/rest) was diminished in preoperative compared with postoperative patients (1.66 +/- 0.44 vs 2.22 +/- 0.85; P less than 0.05) as well as with controls (2.80 +/- 0.84; P less than 0.01), and corresponding coronary resistance ratio (dipyridamole/rest) was higher in preoperative patients than in both other groups (0.61 +/- 0.17 vs 0.48 +/- 0.14; P less than 0.05 vs 0.37 +/- 0.10; P less than 0.01). Differences in the flow ratio, but not in the resistance ratio, were significant (P less than 0.05) in patients after aortic valve replacement compared with controls. Total coronary sinus blood flow at rest was elevated in preoperative compared with both postoperative patients and controls (252 +/- 99 vs 169 +/- 63; P less than 0.01; vs 170 +/- 35 ml.min-1, P less than 0.05), whereas flows after maximal vasodilation did not differ among the three groups (416 +/- 184 vs 361 +/- 150 vs 488 +/- 235 ml.min-1). Postoperative patients showed a distinct, though not total regression of left ventricular angiographic muscle mass index and wall thickness. Nine of the 18 postoperative patients showed a normal coronary flow reserve and nine showed subnormal response. These two subgroups did not differ with respect to preoperative macroscopic and microscopic measures of hypertrophy. Thus in aortic valve disease, the reduced coronary vasodilator capacity is mainly due to an elevated coronary flow at rest, while the maximal coronary blood flow achieved is identical to that of postoperative patients and controls. With regression of left ventricular hypertrophy, flow at rest decreases and this leads to a distinct improvement of coronary flow reserve.

Aged↗

[Concomitance of coronary artery disease with acquired aortic valve disease].

Incidence of concomitant coronary disease and extent of coronary artery lesions were assessed in 250 patients with acquired post-rheumatic aortic valve disease treated between 1976 and 1986 in National Institute of Cardiology. Patients' age ranged from 30 to 72 years. Hemodynamic examination with selective coronarography were performed in patients with typical effort or rest angina pain, with electrographically documented myocardial infarction in the past and also in those without (CAD clinical symptoms, but older than 45 years. Patients were divided into two groups: with isolated or dominated aortic valve stenosis (139 patients) and with isolated or dominated aortic valve incompetence. Patients younger and older than 45 years were separately analyzed. Concomitant CAD was proved if at least one coronary artery stenosis was stated. Lesions degree was proportionally graded: stenosis more than 70%, between 50-70% and 20-50% of a vessel lumen in relation to its diameter before lesion. Data were analyzed using ICL ME 29 computer. Study results indicate, that symptoms of coronary failure were observed in 82.8% of patients with acquired aortic valve disease. In 37% of cases there were critical stenoses requiring simultaneous aortic valve replacement with coronary artery by-pass grafting. Severe coronary artery stenosis was stated in 45% of patients with dominated or isolated aortic valve incompetence, whereas only in 29.3% with dominated or isolated aortic valve stenosis. 88.5% of patients younger than 45 years nevertheless coronary failure symptoms had normal coronary arteries.

Adult↗

Valvular heart disease, Part 1. Diagnosis and surgical management of aortic valve disease in older adults.

Aortic valve disease is a common cause of morbidity and mortality in older patients. The etiology, physical findings, and natural history of aortic stenosis and aortic regurgitation may differ in older patients compared with younger patients. In addition, symptoms of aortic valve disease may be masked or exacerbated by co-existent coronary artery disease, hypertension, pulmonary diseases, and other systemic disorders that commonly occur in the geriatric population. Clinical assessment, along with various non-invasive cardiac techniques including ECG, chest x-ray, and echocardiogram are important in identifying aortic valve disease as the cause of abnormal signs and symptoms in these patients. Recognition of aortic valve abnormalities has important therapeutic implications because aortic valve replacement is usually associated with favorable short- and long-term results, even in patients over age 65.

Age Factors↗

Calcific bicuspid aortic valve disease in a patient with Cornelia de Lange syndrome: linking altered Notch signaling to aortic valve disease.

We describe a patient with Cornelia de Lange syndrome (CdLS) and a severely calcified bicuspid aortic valve. Cornelia de Lange syndrome is characterized by altered Notch signaling, and recent studies have provided a link between Notch signaling and heart valve development and calcific bicuspid aortic valve disease. In this case report, we propose that altered Notch signaling in CdLS may be causally linked to the calcific bicuspid aortic valve disease in these patients. Patients with CdLS should undergo routine echocardiographic examination for possible congenital cardiac defects including bicuspid aortic valve.

Adult↗

Distribution of coronary artery disease in patients with isolate aortic valve disease.

Forty-four adult patients with isolated aortic valve disease underwent coronary arteriography. Seventy precent of patients required aortic valve replacement (AVR). Of 28 men who underwent AVR, 59 percent of those with severe aortic stenosis, 33 percent of those with severe aortic regurgitation and 50 percent of those with mixed aortic stenosis/aortic regurgitation had associated coronary artery disease. Thirty-six percent of men with aortic valve disease not requiring AVR had significant coronary artery disease (CAD). CAD was not found in the 5 female patients studied. In the patients with CAD, the left anterior descending artery was involved 84 percent of the time. Next in frequency were the right coronary artery, the proximal left circumflex artery, and the obtuse marginal artery. Multivessel disease was the rule. All but one patient with significant CAD had angina pectoris, but many patients with angina had normal coronary arteries. The frequent occurence of significant CAD in adult male patients with isolated aortic valve disease argues for the performance of selective coronary arteriography in all such patients in whom AVR is a consideration.

Adult↗

[Surgery for aortic valve disease with congenital bicuspid aortic valve].

From January 1998 to December 2002, a total of 120 patients underwent aortic valve surgery at our institution. Of these, 26 patients (22%) had congenital bicuspid aortic valve (BAV). Main valvular lesion of BAV was aortic valve stenosis (AS) in 17 and regurgitation (AR) in 9. There was no significant difference in the aortic annular size between BAV and non-BAV cases measured by echocardiography preoperatively [22.8 +/- 2.0 mm versus 22.5 +/- 2.2 mm in AS (NS), and 25.4 +/- 2.4 mm versus 23.4 +/- 2.5 mm in AR (NS)]. At operation, however, supraannular type prosthetic valve was selected more frequently in BAV than in non-BAV because of the difficulty of implanting the proper size prosthetic valve in annular position in BAV [10/25 (40%) in BAV versus 18/91 (20%) in non-BAV (p < 0.05)]. Moreover, ascending aortic dimension in BAV cases was significantly larger than in non-BAV cases [43.7 +/- 7.3 mm versus 39.6 +/- 7.3 mm (p<0.05)]. These features were more prominent in non-raphe BAV cases. These results suggested that operative procedure including prosthetic valve selection needs careful consideration in BAV especially no-raphe patients.

Aged↗

Ten years' experience with pulmonary autograft replacements for aortic valve disease.

Pulmonary autograft valves have been used to replace isolated, diseased aortic valves for 10 years, with a long-term survival of 73%. The low incidence of degeneration supports the principle that the autograft valve is a potentially permanent valve replacement. Operative mortality is now less than 5%, despite the longer, more complex operation. The current use of fresh homograft valves for the pulmonary replacement has contributed to these excellent long-term results.

Adolescent↗

Diagnostic implications of figure-of-eight and clockwise QRS loop rotation on the horizontal vectorcardiogram in chronic aortic valve disease.

In chronic aortic valve disease the left ventricular (LV) volumes, mass and ejection fraction (EF), as well as selected Frank ECG measurements of patients with a normal counterclockwise rotation (Type A) of the horizontal QRS vector loop are compared with those of patients showing an abnormal figure-of-eight or clockwise configuration (Type B) to investigate whether the different QRS patterns reflect ventriculographic alterations or depends on a conduction delay. In aortic stenosis (AS,n = 21) and combined AS and aortic insufficiency (AS + AI,n = 23) the Type B vectorcardiograms (VCGs) correlate with significantly increased LV end-diastolic volumes (p. .01, .01, respectively) and depressed EF (p .07, .009, respectively). In pure AI (n = 39) LV volumes, mass and EF do not differ between the Type A and Type B patterns. As compared to Type B VCGs of AS (n = 6), the LV end-diastolic volume index is clearly higher in Type A VCGs of pure AI (n = 21)(p .028). The only ECG change which is significant at the p .01 level in each group is the increase of the R peak time in lead X in the Type B VCGs. This can be related to greater volume and mass only in AS and AS+ AI, but is not substantiated by equivalent ventriculographic alterations in pure AI. The findings indicate that Type B VCGs are very likely caused by a left ventricular conduction delay since they cannot be strictly correlated with increases in LV volume and mass alone.

Adult↗

Exercise testing and thallium-201 myocardial imaging in relation to coronary artery disease in patients with severe aortic valve disease.

Thirty-three patients with aortic valve disease, fifteen with regurgitation, eleven with stenosis and seven with mixed disease, undergoing assessment for valve replacement which included adequate coronary angiography, were studied. A symptom limited graded treadmill exercise test was undertaken with administration of 40-70 MBq of 201Tl. Myocardial imaging was started within 15 minutes and repeated after four hours using a 37 PM tube Searle gamma camera. Myocardial images were read independently by three observed. Of the 33 sets of images, 21 were -ve, 5 +ve, 2 I (Indeterminate) and 5 D (Difference of opinion). Eight of the 33 patients had significant coronary artery disease (CAD) and of these three were scored +ve (all triple vessel). Two patients without CAD were scored +ve. Eight subjects developed angina during exercise testing, of whom four had CAD, and four with CAD did no develop angina. Historically, 13 of the 33 subjects had typical angina, six having CAD; an additional eight had other significant chest pain, two having CAD. In these subjects with severe aortic valve disease, exercise testing and myocardial imaging with 201 TI was of little value in detecting CAD. All patients with CAD gave a history of significant chest pain.

Adult↗

Hypertension in aortic valve disease and its response to valve replacement.

We have investigated the prevalence of hypertension and the response of blood pressure to operation in 87 patients with lone aortic valve disease who underwent aortic valve replacement. In patients with aortic stenosis alone 26% were hypertensive pre-operatively (age and sex adjusted blood pressure greater than 160 systolic and or greater than 95 mmHg diastolic) and 24% were hypertensive post-operatively. In those with aortic regurgitation alone, hypertension was present in 65% before and 57% after valve replacement using the same criterion. For combined stenosis and regurgitation, the prevalence was 54% and 62%, respectively. The post-operative increase in systolic pressure in patients with aortic stenosis occurred mainly in those with a history of left ventricular failure. In those with aortic regurgitation or combined stenosis with regurgitation, diastolic pressure rose after valve replacement resulting in a prevalence of diastolic hypertension of 44% and 35%, respectively. Blood pressure changes were not predicted by the type of valve inserted nor its size. Our data show that despite severe symptomatic aortic valve disease, systolic hypertension was common in aortic stenosis and diastolic hypertension was found in aortic regurgitation. This underlines the importance of blood pressure monitoring in patients following aortic valve replacement.

Adult↗

Angina and coronary artery disease in patients with aortic valve disease.

The significance of angina pectoris in patients with aortic valve disease (AVD) and the need for coronary arteriography before valve replacement are controversial. The history of chest pain and coronary arteriographic findings were reviewed in 333 patients > or = forty years old, with AVD: 142 with aortic stenosis, 87 with mixed AVD and 104 with aortic regurgitation. The prevalence of coronary artery disease (CAD) was similar among different types of AVD. Angina pectoris was more frequent in patients with aortic stenosis (56%) and mixed AVD (53%) than in patients with aortic regurgitation (24%) (p < 0.0001). Similar results were found in patients with and without CAD. Twenty-six of 95 (27%) patients with CAD had no chest pain at all. The absence of any chest pain in CAD patients was more frequent in those > or = sixty years old than in those < sixty (p < 0.05). Thus, since a significant number of patients had CAD in the absence of any chest pain, the authors recommend coronary arteriography for all patients > or = forty years of age before aortic valve replacement.

Aged↗