Chronic Severe Aortic Regurgitation Research Articles

Aortic Insufficiency

Major advances in the diagnostic, evaluation, and particularly surgical treatment of aortic regurgitation (AR) have redefined the role of medical treatment. In acute AR, aortic valve replacement (AVR) is the only life-saving treatment. Medical treatment may improve the hemodynamic state temporarily before surgery. Rationale of medical treatment in chronic AR is based on the natural history and pathophysiology of the disease. The primary goal is to optimize the time of the AVR. If there is any symptom and/or left ventricular (LV) dysfunction, early AVR is required. Vasodilators should only be considered as a short-term treatment before surgery if there is evidence of severe heart failure or as a long-term treatment if AVR is contraindicated because of cardiac or noncardiac factors. In asymptomatic patients with severe chronic AR and normal LV function (even if the left ventricle is moderately dilated), vasodilators may prolong the compensated phase of chronic AR, although proof of their efficacy in delaying AVR is limited. Nifedipine is the best evidence-based treatment in this indication. ACE inhibitors are particularly useful for hypertensive patients with AR. beta-Adrenoceptor antagonists (beta-blockers) may be indicated to slow the rate of aortic dilatation and delay the need for surgery in patients with AR associated with aortic root disease. Furthermore, they may improve cardiac performance by reducing cardiac volume and LV mass in patients with impaired LV function after AVR for AR.

1030-135 Impact of wide pulse pressure with and without high systolic blood pressure on clinical outcomes in chronic severe aortic regurgitation

excluded. Results: We identified 114 patients (Mean age 59+/-15yrs; 79% male), 39 (34.2%) had isolated aortic cusp prolapse and 73 (64%) had restricted cusp motion as the primary mechanism of AR. Valve repair was performed in 26 (22.8%).Two of these patients had failed repairs requiring valve replacement. Repair was more likely in younger patients, those with leaflet prolapse, tless leaflet edge thickening and less commissural calcification. By multivariate analysis, eccentric AR jet direction and less leaflet edge thickening (</= 3mm), emerged as independent determinants of likelihood of successful valve repair Conclusions: A number of echo features predict valve reparability in patients with trileaflet aortic valves, intrinsic valve pathology and primary isolated AR, with eccentric regurgitant jet direction and less leaflet edge thickness being the most important.

843 Regional myocardial function in patients with chronic severe aortic regurgitation before and after aortic valve surgery

843 Regional myocardial function in patients with chronic severe aortic regurgitation before and after aortic valve surgery

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology

Ten-year clinical laboratory follow-up after application of a symptom-based therapeutic strategy to patients with severe chronic aortic regurgitation of predominant rheumatic etiology

ObjectivesThis study was designed to assess the feasibility and the long-term results of a symptom-based strategy of aortic valve replacement in a Brazilian population with predominant rheumatic etiology. BackgroundOptimal criteria for valve replacement in aortic regurgitation (AR) are still not entirely clear. The appearance of symptoms is an indication for surgery, but may be associated with myocardial damage. Although cardiac imaging data have provided a safer guide for such decisions, the use of symptom-based surgical indication has not been validated and might conceivably be better in populations with predominant rheumatic etiology and younger age. MethodsEchocardiography and rest-exercise radionuclide ventriculography were performed in 75 patients with severe AR, age 28 ± 9 years, over a period of 10 ± 0.69 years. Thirty-seven patients developed symptoms and underwent aortic valve replacement surgery within six months. Thirty-eight patients remained asymptomatic and were managed medically. ResultsSurvival was 100% in asymptomatic patients and 82% in symptomatic. Surgical treatment caused marked ventricular remodeling, with ventricular diameter involution and an improvement of rest-exercise ejection fraction percent variation. Multivariate analysis showed that the probability of developing symptoms within 10 years was 58% for a patient with a left ventricular end-diastolic diameter ≥70 mm and 76% for a patient with left ventricular end-systolic (LVESD) ≥50 mm. Logistic regression identified LVESD and age as the most predictive and specific, but not sensitive, indicators of symptom development. ConclusionsApplication of a standardized therapeutic strategy to patients with severe AR and predominant rheumatic etiology resulted in 90.6% survival after 10 years of follow-up.

Impact of systolic hypertension and impedance lowering drugs on clinical outcomes in chronic severe aortic regurgitation

Impact of systolic hypertension and impedance lowering drugs on clinical outcomes in chronic severe aortic regurgitation

Impact of vasodilator use on adverse events in chronic severe aortic regurgitation

Impact of vasodilator use on adverse events in chronic severe aortic regurgitation

Arterial distensibility as a possible compensatory mechanism in chronic aortic insufficiency.

To evaluate elastic properties of conduit arteries in asymptomatic patients who have severe chronic aortic regurgitation. Twelve healthy volunteers aged 30+/-1 years (control group) and 14 asymptomatic patients with severe aortic regurgitation aged 29+/-2 years and left ventricular ejection fraction of 0.61+/-0.02 (radioisotope ventriculography) were studied. High-resolution ultrasonography was performed to measure the systolic and diastolic diameters of the common carotid artery. Simultaneous measurement of blood pressure enabled the calculation of arterial compliance and distensibility. No differences were observed between patients with aortic regurgitation and the control group concerning age, sex, body surface, and mean blood pressure. Pulse pressure was significantly higher in the aortic regurgitation group compared with that in the control group (78+/-3 versus 48+/-1mmHg, P<0.01). Arterial compliance and distensibility were significantly greater in the aortic regurgitation group compared with that in the control group (11.0+/-0.8 versus 8.1+/-0.7 10(-10) N-1 m4, P=0.01 e and 39.3+/-2.6 versus 31.1+/-2.0 10(-6) N-1 m2, P=0.02, respectively). Patients with chronic aortic regurgitation have increased arterial distensibility. Greater vascular compliance, to lessen the impact of systolic volume ejected into conduit arteries, represents a compensatory mechanism in left ventricular and arterial system coupling.

Natural history of left ventricular function and size in asymptomatic patients with chronic severe aortic regurgitation and initially normal resting function: Relation of temporal patterns to adverse cardiac outcome Phyllis G. Supino, Jeffrey S. Borer, Clare A. Hochreiter, Edmund M. Herrold, Richard B. Devereux, Mary J. Roman, Paul Kligfield, Andrew Yin. Weill Medical College of Cornell University, New York, NY

Natural history of left ventricular function and size in asymptomatic patients with chronic severe aortic regurgitation and initially normal resting function: Relation of temporal patterns to adverse cardiac outcome Phyllis G. Supino, Jeffrey S. Borer, Clare A. Hochreiter, Edmund M. Herrold, Richard B. Devereux, Mary J. Roman, Paul Kligfield, Andrew Yin. Weill Medical College of Cornell University, New York, NY

16.11 Repeat testing of exercise ejection fraction at five years enhances prediction of adverse outcome in asymptomatic patients with chronic severe aortic regurgitation and normal ejection fraction at rest

16.11 Repeat testing of exercise ejection fraction at five years enhances prediction of adverse outcome in asymptomatic patients with chronic severe aortic regurgitation and normal ejection fraction at rest

Study of the value of corrected ejection fraction in the evaluation of left ventricular function in patients with mitral or aortic regurgitation.

Evaluation of left ventricular function in the presence of valvular regurgitation is still a clinical problem because ejection phase indices including ejection fraction are heavily dependent on preload and afterload and cannot be regarded as reliable indices of contractility in diseases associated with altered loading conditions. The authors attempted to evaluate the usefulness of the new index-corrected ejection fraction in the evaluation of left ventricular (LV) function in patients with chronic mitral (MR) or aortic regurgitation (AR). The study included 21 patients with chronic severe MR (11 patients) and AR (10 patients) with a mean age of 18 years. All patients underwent valve replacement or repair. Echo Doppler study was performed preoperatively and postoperatively and included measurement of the following LV parameters: end-diastolic dimension (EDD), end-diastolic volume (EDV), end-systolic dimension (ESD), end-systolic volume (ESV), ejection fraction (EF), systolic blood pressure/end-systolic dimension (SBP/ESD); also mitral and aortic stroke volume were calculated cross-sectional area (CSA) x time velocity integral TVI. Corrected ejection fraction (EFc) was derived from the following equation: EFc = [EF + square root of (ASV x MSV) / EDV] / 2. The mean preoperative EFc did not change significantly after surgical correction of mitral or aortic regurgitation. Preoperative EFc did not show significant difference compared with postoperative EF in the two groups. Preoperative EFc correlated significantly with other preoperative and postoperative indices of LV function. Postoperative EFc showed very close correlation with other postoperative parameters. Thus, using the new index-corrected ejection fraction in the assessment of LV function in patients with mitral or aortic regurgitation has several advantages: Noninvasive, independent of loading changes, helpful in predicting the immediate postoperative clinical course, and a reliable index for evaluation of LV systolic function preoperatively and postoperatively.

Timing of surgery in chronic aortic regurgitation.

When deciding on therapy for aortic regurgitation (AR), it is imperative to distinguish between acute and chronic AR. Symptoms and echocardiographic findings are essential in distinguishing acute from chronic AR and in assessing the severity. Vasodilators have been shown to be helpful in treating patients with chronic severe AR. The timing of aortic valve replacement in chronic severe AR remains controversial. Symptoms, left ventricular function, and response to exercise have been shown to be the most important prognostic indicators.

Symptoms, left ventricular function, and timing of valve replacement surgery in patients with aortic regurgitation

Background Because cardiac decompensation is subtle, the best time to perform aortic valve replacement surgery may be difficult to determine. We investigated the relation of symptoms to left ventricular (LV) function and the timing of valve replacement in patients with aortic regurgitation (AR) of largely rheumatic origin. Methods Sixty-eight initially asymptomatic patients (mean age 29 years) with severe chronic AR were monitored for 36 months. Assessments included baseline and yearly echocardiograms and radioisotope ventriculography (resting and exercise) and clinical examinations every 6 months. Results Forty-seven patients (69%) remained asymptomatic and 21 (31%) had symptoms develop after 24 to 36 months. Compared with symptomatic patients, asymptomatic patients had significantly ( P < .05) lower baseline LV end-diastolic diameter, end-systolic diameter, end-systolic stress, and volume/mass ratio but greater shortening fraction and ejection fraction (EF) at rest. These variables remained stable without statistically significant change until surgical correction in symptomatic patients. Percent variation of EF from rest to exercise increased in patients who remained asymptomatic (EF 2.8% ± 10.6%) but decreased in those who became symptomatic (EF –4.2% ± 13%; P < .05). Twenty symptomatic patients (New York Heart Association class III/IV, angina and/or syncope) had valve replacement surgery, after which all were in New York Heart Association class I/II and had significant decreases of LV end-diastolic and end-systolic diameters and an increase on percent variation of EF from rest to exercise ( P < .0001). Conclusions Development of symptoms did not correlate with change in any ventricular function indexes. Surgery on appearance of symptoms restored LV function to near normal. (Am Heart J 1999;138:477-85.)

Unloading long term effect of enalapril in asymptomatic patients with severe chronic aortic regurgitation

Unloading long term effect of enalapril in asymptomatic patients with severe chronic aortic regurgitation

Relation of Ultra-Low Frequency Heart Rate Variability to the Clinical Course of Chronic Aortic Regurgitation

We examined the relation of the standard deviation of the 5-minute mean RR intervals over 24 hours (SDANN), a measure of ultra-low frequency heart rate variability (HRV) (<0.0033 Hz), and other measures of HRV to clinical outcome events in 50 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation (AR) who underwent ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular diseases. At entry, all patients were in sinus rhythm and had New York Heart Association functional class I or minimal II congestive heart failure, with left ventricular (LV) ejection fraction ≥45% and LV end-diastolic dimension ≥5.5 cm in women and ≥5.9 cm in men. End points were defined as progression to aortic valve replacement (n = 19) or sudden cardiac death (n = 1) during the mean follow-up period of 8.1 ± 3.8 years. With the median SDANN of 145 ms as a partition value, the average annual risk of end-point events in patients with low SDANN was significantly greater than the event rate in patients with high SDANN (11%/year vs 2%/year, p <0.0003). In multivariate analysis, reduced SDANN was associated with end-point events independent of LV function, LV end-systolic dimension, and symptom status (p = 0.001). We conclude that reduced ultra-low frequency HRV measured as SDANN is strongly related to progression to valve surgery in asymptomatic and minimally symptomatic patients with chronic AR.We examined the relation of the standard deviation of the 5-minute mean RR intervals over 24 hours (SDANN) and other measures of heart rate variability to progression to aortic valve replacement or sudden death over a mean 8-year follow-up in 50 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation who had normal left ventricular ejection fraction at rest. With the median SDANN of 145 ms as a partition value, the average annual risk of end-point events in patients with low SDANN was significantly greater than the event rate in patients with high SDANN (11%/year vs 2%/year, p <0.0003), and SDANN was associated with end-point events independent of ventricular function, left ventricular end-systolic dimension, and symptom status.

Retrograde atrial kick in acute aortic regurgitation. Study of mitral and pulmonary venous flow velocities by transthoracic and transesophageal echocardiography.

The purpose of this study was the comprehensive evaluation of the changes in pulmonary venous and mitral flow velocities of patients with acute and chronic severe aortic regurgitation. Transmitral flow velocities obtained with pulsed-wave Doppler echocardiography have been used to provide information on left ventricular (LV) filling and diastolic function. Pulmonary venous flow tracings are an important adjunct to LV inflow pattern in assessing LV diastolic function. Fourteen patients with severe aortic regurgitation (8 chronic and 6 acute) and in sinus rhythm were examined by transthoracic and transesophageal pulsed Doppler echocardiography. Mitral and pulmonary flow velocities were recorded and compared. All patients had ejection fractions > 40%. Early mitral flow peak velocity was higher in patients with acute regurgitation (p < 0.001). The mitral A wave was absent in five patients with acute regurgitation. In contrast, a prominent reverse atrial pulmonary systolic wave AR was demonstrated in these patients. Peak diastolic velocity of the pulmonary venous flow was greater in patients with acute aortic regurgitation (0.76 +/- 0.13) than in patients with chronic aortic regurgitation (0.40 +/- 0.09) (p < 0.001). Peak systolic velocity did not differ significantly between the two groups. The systolic fraction of pulmonary venous flow in patients with acute aortic regurgitation was lower (0.43 +/- 0.05) than that of patients with chronic regurgitation (0.63 +/- 0.1) (p < 0.01). All patients with acute aortic regurgitation had an S/D ratio < 1, while those with chronic regurgitation had an S/D > 1 (p < 0.001) and an E/A < 1. Patients with severe acute aortic regurgitation showed a retrograde atrial kick (absence of transmitral A wave with prominent pulmonary AR wave). These patients had an S/D ratio < 1 (restrictive Doppler pattern). Patients with chronic aortic regurgitation exhibited a Doppler pattern of abnormal LV relaxation (E/A < 1, S/D > 1).

Transesophageal Doppler echocardiographic assessment of systolic and diastolic coronary blood flow velocities at baseline and during adenosine triphosphate–induced coronary vasodilation in chronic aortic regurgitation

Few reports exist on the changes in systolic and diastolic coronary flow velocities (CFVs) at baseline and during coronary vasodilation in patients with chronic aortic regurgitation (AR). We examined the left anterior descending CFVs in 21 patients with AR (11 patients with mild AR and 10 patients with moderate to severe AR), 9 patients without AR (no AR group), and 6 patients who had undergone surgery for moderate to severe AR (postoperation group) with transesophageal Doppler echocardiography. Adenosine triphosphate (ATP) was infused into a peripheral right arm vein at four different doses (35, 70, 100, and 140 μg/kg/min). Coronary flow velocity response in systole and diastole was calculated as the ratio of systolic peak and mean and diastolic peak and mean CFVs during maximal ATP infusion to those at baseline. The systolic peak and mean CFVs and the diastolic peak and mean CFVs at baseline were significantly increased in the moderate to severe group compared with those in the other groups ( p < 0.05, respectively). Systolic and diastolic CFVs were significantly increased during ATP infusions in the four groups. No significant differences of systolic and diastolic CFVs were observed among the four groups during maximal ATP infusion. The coronary flow velocity response calculated from the peak and mean diastolic CFVs were significantly decreased in the moderate to severe group (1.6 ± 0.3 and 1.7 ± 0.4) compared with those in the other three groups (3.6 ± 0.7 and 3.2 ± 1.1 in the no AR group, 2.6 ± 0.6 and 2.5 ± 0.4 in the mild group, and 2.5 ± 0.7 and 2.4 ± 0.6 in the postoperation group) ( p < 0.05, respectively). In conclusion, the systolic and diastolic left CFVs at baseline appeared to be significantly increased in patients with moderate to severe chronic AR. However, the velocities during coronary vasodilation by ATP were equal to those in other groups, resulting in a decrease of coronary flow velocity response in systole and diastole. (Am Heart J 1997;133:71-7.)

Clinical outcome of severe asymptomatic chronic aortic regurgitation: A long-term prospective follow-up study

One hundred one patients with asymptomatic chronic severe aortic regurgitation and normal ejection fraction were monitored for up to 10 years (mean 55.4 ± 33.5 months). Predefined surgical indications were the development of cardiac symptoms or the documentation of impaired basal left ventricular function. During the follow-up period there were no cardiac deaths; 14 patients needed surgery, 8 because of development of symptoms and 6 because of left ventricular impairment. The risk of surgery was 12% at 5 years and 24% at 10 years. Baseline end-systolic diameter >50 mm and radionuclide ejection fraction <60% were independent predictors or either cardiac symptoms or left ventricular dysfunction. In patients needing surgery, a pattern of progressive left ventricular dilatation was demonstrated. There were no deaths during surgery, and echocardiographic and radionuclide parameters normalized in the first year of follow-up. Our data confirm that the prognosis of severe aortic regurgitation in patients with no symptoms is good and that the occurrence of asymptomatic left ventricular dysfunction is an uncommon event. Surgery can be safely postponed until the appearance of cardiac symptoms or the documentation of left ventricular dysfunction at rest.

975-81 Prognostic Value of Ultra-Low Frequency Heart Rate Variability in Chronic Aortic Regurgitation

Ultra-low frequency heart rate variability can predict progression to valve surgery or cardiac death in patients with mitral regurgitation, but its prognostic value in patients with chronic pure aortic regurgitation has not been defined. We examined heart rate variability in 46 asymptomatic or minimally symptomatic patients with chronic severe aortic regurgitation and no evident coronary disease, who underwent ambulatory electrocardiography as part of a prospective study of the natural history of regurgitant valvular diseases. At entry, all patients were in sinus rhythm, and were NYHA functional class I or early II, with left ventricular ejection fraction ≥ 45%, left ventricular dimension in diastole (LVIDd) ≥ 5.5 cm in females, LVIDd ≥ 5.9 cm in males. Endpoints were progression to aortic valve replacement (n = 19) or cardiac death (n = 1). A measure of ultra-low frequency heart rate variability, SDANN, was calculated as the standard deviation of the 5 minute mean RR intervals over 24 hours. Based on a median SDANN of 144 msec as a partition value, event-free survival in patients with SDANN &lt;144 msec (n = 23) was compared to that in patients with SDANN ≥ 144 msec (n = 23) using the log rank test, as shown in the figure. The average annual risk of endpoint events was 10.2% for SDANN &lt;144 msec and 2.6% for SDANN ≥ 144 msec (p = 0.003). Ultra-low frequency heart rate variability measured as SDANN strongly concentrates risk of progression to valve surgery or cardiac death in asymptomatic and minimally symptomatic patients with chronic pure aortic regurgitation

Vasodilator therapy in chronic asymptomatic aortic regurgitation: Enalapril versus hydralazine therapy

Objectives. This study attempted to evaluate the long-term effcacy of enalapril versus hydralazine therapy on left ventricular volume, mass and function as well as on the renin-angiotensin system in chronic asymptomatic aortic regurgitation.Background. We tested the hypothesis that early administration of a vasodilator drag might be able to reduce left ventricular dilution and mass expansion. Because the renin-angiotensin system may be activated in chronic aortic regurgitation, early enalapril therapy might be beneficial.Methods. Between 1990 and 1993, 76 asymptomatic nonrheumatic patients with mild to severe chronic aortic regurgitation were enrolled in a randomized, double-blind trial comparing enalapril with hydralazine. All patients underwent serial noninvasive studies. Seventy patients completed the 12-month follow-up.Results. At 1 year, patients receiving enalapril had a significant reduction in left ventricular end-diastolic and end-systolic volume indexes (124 ± 15 vs. 108 ± 17 ml/m2, p < 0.01; 50 ± 12 vs. 40 ± 14 ml/m2, p < 0.01, respectively) and mass index (131 ± 16 vs. 113 ± 19 g/m2, p < 0.01), wheress hydralazine therapy showed no significant changes. Both regimens not only had a significant reduction in left ventricular mean wall stress but also had a mild increase in exercise duration. Only enalapril therapy achieved a significant inhibition of the renin-angiotensin system, in contrast to hydralazine therapy. Moreover, the multiple r2value from the analysis for end-diastolic volume index using the two variables of age and treatment drugs was 72.1% (p < 0.01).Conclusions. Both regimens decrease left ventricular mean wall stress. Enalapril therapy achieves significant left ventricular mass regression, left ventricular end-diastolic and end-systolic volume index reduction and renin-angiotensin system suppression. These findings suggest that early unloading enalapril therapy has the potential to favorably influence the natural history of chronic aortic regurgitation.