Chronic Aortic Regurgitation Research Articles

Assessment of Myocardial Velocities and Global Function of the Left Ventricle in Asymptomatic Patients with Moderate‐to‐Severe Chronic Aortic Regurgitation: A Tissue Doppler Echocardiographic Study

Asymptomatic patients with chronic aortic regurgitation (AR) have an excellent prognosis in the presence of preserved systolic function. It is a challenge to recognize patients with subclinical myocardial dysfunction in AR. Conventional parameters still have many drawbacks in predicting early left ventricular (LV) dysfunction. Pulsed-wave tissue Doppler imaging (PW-TDI) is a useful noninvasive technique for evaluating global and regional LV systolic function. In this study, we aimed to assess clinical usefulness of TDI in predicting early disturbance of myocardial contractility in asymptomatic patients with significant AR and preserved left ventricular systolic function. Echocardiograms were obtained in 32 AR patients and 33 healthy subjects. In addition to conventional parameters, regional myocardial velocities, isovolumetric contraction time (mICT), isovolumetric relaxation time (mIRT), and ejection time (mET) of left ventricle were obtained by TDI and modified LV myocardial performance index (MPI) was calculated. In AR, peak systolic velocity (Sm) of septal and anterior mitral annulus, and mean Sm was significantly lower, and LVMPI was significantly higher compared to control group. The data obtained by TDI show that LV MPI is lengthened, and systolic myocardial velocities are shortened in patients having chronic AR with normal LV systolic function according to conventional echocardiographic parameters. This suggests that LV long-axis contraction and global LV performance are preciously and noticeably decreased in patients with moderate-to-severe chronic AR despite normal LV ejection fraction.

Improved Outcomes After Aortic Valve Surgery for Chronic Aortic Regurgitation With Severe Left Ventricular Dysfunction

Among patients undergoing aortic valve surgery for chronic aortic regurgitation (AR), we sought to: 1) compare survival among those with and without severe left ventricular dysfunction (LVD); 2) identify risk factors for death, including LVD and date of operation; and 3) estimate contemporary risk for cardiomyopathic patients. Patients with chronic AR and severe LVD have been considered high risk for aortic valve surgery, with limited prognosis. Transplantation is considered for some. From 1972 to 1999, 724 patients underwent surgery for chronic AR; 88 (12%) had severe LVD. They were propensity matched to patients with nonsevere LVD to compare hospital mortality, interaction of operative date with severity of LVD, and late survival. Propensity score-adjusted multivariable analysis was performed for all 724 patients to identify risk factors for death. Survival was lower (p = 0.04) among patients with severe LVD than among matched patients with nonsevere LVD (30-day, 1-, 5-, and 25-year survival estimates were 91% vs. 96%, 81% vs. 92%, 68% vs. 81%, and 5% vs. 12%, respectively). However, survival of patients with severe LVD improved dramatically across the study time frame (p = 0.0004): hospital mortality decreased from 50% in 1975 to 0% after 1985, and time-related survival in patients with severe LVD operated on since 1985 became equivalent to that of matched patients with nonsevere LVD (p = 0.96). Neutralizing risk of severe LVD has improved early and late survival such that aortic valve surgery for chronic AR and cardiomyopathy is no longer a high-risk procedure for which transplantation is the best option.

Large Mural Vegetation Attached to the Left Ventricular Outflow Tract: A Case Report

We describe an unusual case of staphylococcal endocarditis with vegetation attached to the left ventricular outflow endocardium in a patient with chronic severe aortic regurgitation that was diagnosed by transthoracic echocardiography. There was no involvement of aortic valve endocardium confirmed by transthoracic echocardiography, transesophageal echocardiography, and macroscopically in the operation. This report confirms that chronic endocardial trauma may provide a fertile nidus for the development of bacterial vegetation.

Genetic Disruption of Angiotensin II Type 1a Receptor Improves Long-Term Survival of Mice With Chronic Severe Aortic Regurgitation

Aortic regurgitation (AR) causes left ventricular (LV) volume overload, leading to progressive LV dilatation and dysfunction. In the present study it was examined whether blockade of angiotensin II type 1 receptor (AT1) could improve survival in cases of chronic severe AR. AR was induced by puncturing the aortic valves of wild-type (WT) and AT1a knockout (KO) mice. Mice that survived for 4 weeks after the operation were deemed to be a model of chronic severe AR and were followed up for 50 weeks (WT, n=29; KO, n=31). Baseline measurements made 4 weeks after surgery showed similar LV cavity and function in both genotypes. These conditions progressively worsened in both genotypes, but 16 weeks after baseline, KO mice showed significantly less LV dilatation, hypertrophy and interstitial fibrosis than WT mice. Cardiac mRNA expression of B-type natriuretic peptide and type I collagen was lower in KO than WT mice. The 50-week mortality rate was significantly lower among KO (45.2%) than WT (86.2%) mice, and postmortem findings indicated that the lower mortality was attributable to a lower incidence of congestive heart failure. In cases of chronic severe AR, blockade of AT1 attenuates the progression of LV dilatation, hypertrophy and fibrosis, thereby mitigating heart failure and improving long-term survival.

Myocardial T1 Mapping for Detection of Left Ventricular Myocardial Fibrosis in Chronic Aortic Regurgitation: Pilot Study

The aim of this study was to identify diffuse myocardial fibrosis secondary to chronic aortic regurgitation by comparing the T1 relaxation times of left ventricular myocardium in a pilot patient group with a previously established normal range of times. Eight patients with chronic aortic regurgitation and normal coronary arteries awaiting surgical valve replacement underwent a comprehensive MRI examination that included assessment of left ventricular function, severity of valvular regurgitation, and presence of overt myocardial scar evidenced by delayed enhancement. For each patient, myocardial T1 relaxation times determined with a modified Look-Locker technique before and after contrast administration were compared with values previously established for 15 healthy volunteers. There was no statistical difference (p > 0.05) in slice-averaged myocardial T1 relaxation times either before or after gadolinium administration in the patient group compared with the normal range of times. Segmental averaged T1 relaxation times in segments with abnormal wall motion did, however, show statistically significant differences from healthy controls 10, 15, and 20 minutes after administration of gadolinium (510 vs 476 milliseconds, p = 0.001; 532 vs 501 milliseconds, p = 0.002; 560 vs 516 milliseconds, p = 0.001, respectively). Two of the aortic regurgitation patients also had focal areas of myocardial delayed enhancement. Segment-based myocardial T1 mapping has the potential for showing differences between relaxation times in aortic regurgitation and in normal hearts, suggesting the existence of a diffuse myocardial fibrotic process.

433 Preoperative systolic strain rate predicts postoperative left ventricular systolic function in patients with chronic aortic regurgitation

433 Preoperative systolic strain rate predicts postoperative left ventricular systolic function in patients with chronic aortic regurgitation

975 Echocardiographic evaluation of valvular cardiomyopathy using tissue doppler imaging in chronic severe aortic regurgitation

975 Echocardiographic evaluation of valvular cardiomyopathy using tissue doppler imaging in chronic severe aortic regurgitation

Impact of Anesthesia on Echocardiographic Evaluation of Systolic and Diastolic Function in Rats

Echocardiography is used on rats but general anesthesia is usually necessary to be able to obtain a good quality echocardiogram. Each type of anesthetic agent has specific impacts on hemodynamics and, therefore, may affect differentially the echocardiographic measurements. We sought to compare the echocardiograms of normal rats and rats with chronic aortic regurgitation under anesthesia using ketamine-xylazine or isoflurane. Animals underwent an echocardiogram with both drugs sequentially. Echocardiographic measurements were compared. Mitral diastolic Doppler measurements (early diastolic filling wave [E] and late atrial diastolic filling wave [A] velocities) were significantly affected by the type of anesthesia in the normal group but not left ventricular dimensions or ejection fraction. Left ventricular dimensions were affected by the type of anesthesia in the aortic regurgitation group and diastolic Doppler flow. The anesthetic agent has significant specific impacts on many echocardiographic measurements. Investigators working with rat models should be aware of those potential effects.

Kontrastní zátěžová echokardiografie u asymptomatické chronické významné aortální regurgitace

Kontrastní zátěžová echokardiografie u asymptomatické chronické významné aortální regurgitace

Thinking beyond the risk factors☆

For each risk factor for Black Death he discovered, John Graunt in 1662 made a recommendation for action, such as fleeing the night air brought to the City of London docks on foreign ships. These stopped the plague for 200 years! In this honored guest lecture, I focus on thinking beyond the risk factors to their neutralization by effective action without waiting for perfect knowledge of mechanisms. For example, the decreasing risk of repairing atrioventricular septal defect resulted from risk factors that stimulated focused research to devise a better operation. General reduction in risk reduced mortality of aortic valve replacement in patients with chronic aortic regurgitation and severe left ventricular dysfunction. Optimal timing of surgery after stabilizing patients reduced risk of the Norwood procedure. Managing intractable cardiogenic shock reduced risk-adjusted mortality in post-infarct ventricular septal defect. However, we must think beyond traditional risk factors to neutralization of those brought by patient characteristics, imponderables, treatment delivery systems, institutions delivering care to groups of patients, and society caring for its population. There are limitations to thinking beyond risk factors. First, neutralizing strategies require improving processes or introducing new ones. Yet there may be process-outcome disconnect, or even counterintuitive or contradictory relations among outcomes and what are thought to be best processes. Nevertheless, thinking beyond risk factors to their neutralization by research, innovation, and application of knowledge can be as spectacularly successful as was fleeing foul air in halting Black Death.

Long-Term Outcome of Surgically Treated Aortic Regurgitation: Influence of Guideline Adherence Toward Early Surgery

The purpose of this study was to compare postoperative outcome in two groups of patients with chronic severe aortic regurgitation (AR): those operated on early and those operated on late according to the guidelines. The impact of earlier surgery for chronic severe AR as defined in guidelines has not been evaluated. A total of 170 patients with chronic severe AR submitted to aortic valve replacement were prospectively followed up. Patients were divided in two groups depending on the clinical situation at the time of surgery. Group A were 60 patients who were operated on following guidelines advice of earlier surgery, and group B were 110 patients who were operated on late with regard to guideline recommendations. Follow-up was 10 +/- 6 years (1 to 22 years). During follow-up 44 patients died, 7 patients (12%) from group A and 37 (37%) from group B (p = 0.001). The cause of death was non-cardiac in 11 patients, 2 (3%) in group A and 9 (8%) in group B. Cardiac deaths occurred in 33 patients, 5 (9%) from group A and 28 (28%) from group B (p = 0.002). Causes of death differed between groups A and B: heart failure or sudden death were significantly more frequent in group B (20 patients vs. 1 patient, p = 0.001). Overall survival in groups A and B was 90 +/- 4% vs. 75 +/- 8% at 5 years, 86 +/- 5% vs. 64 +/- 5% at 10 years, and 78 +/- 7% vs. 53 +/- 6% at 15 years, respectively (p = 0.009). Early operation as defined in the guidelines improves long-term survival in patients with chronic AR.

The Usefulness of 2-Dimensional Longitudinal Strain for Prediction of the Postoperative Left Ventricular Systolic Function in Patients with Valvular Heart Disease Causing Volume Overloading

Background and Objectives:Prediction of the postoperative left ventricular (LV) function in valvular heart disease that will cause LV volume overloading, such as chronic mitral regurgitation (MR) and aortic regurgitation (AR), remains elusive. We sought to test if 2-dimensional peak negative longitudinal strain (LS2D) was useful for prediction of the postoperative LV function in relation to this disease entity. Subjects and Methods:Newly developed speckle tracking imaging was performed preoperatively to measure the LS2D in 26 and 22 patients with MR and AR, respectively. A favorable response after the operation (FR) was defined according to the change in the LV ejection fraction (EF): 1) a LVEF ≥55% both preand post-operation, 2) a postoperative LVEF ≥55% with a pre-operative LVEF between 10% with a pre-operative LVEF <45%. Results:Follow-up echocardiography was performed at an average of 6.7±2.3 months after the operation. FR was confirmed in 36 patients (LVEF from 55.4±10.1 to 58.3±5.0%, p=0.06), with the remaining 12 showing an unfavorable response (LVEF from 52.5±7.6 to 45.1±5.4%, p<0.01). There was no significant difference in the baseline characteristics, including underlying etiologies, operation techniques, and cardiopulmonary bypass time, and LV volumes and EF between the two groups. The only difference was the LS2D, which was significantly larger in the FR group (-19.8±3.9 versus -16.2±2.9%, p<0.01). An LS2D of -18.3% could predict an unfavorable response of the LVEF following an operation, with a sensitivity and specificity of 75 and 75%, respectively. Conclusion:The preoperative LS2D is a useful predictor of the postoperative left ventricular function in AR and MR. (Korean Circulation J 2006;36:272-278)

Long-term Survival and Functional Results After Aortic Valve Replacement in Asymptomatic Patients With Chronic Severe Aortic Regurgitation and Left Ventricular Dysfunction

Long-term Survival and Functional Results After Aortic Valve Replacement in Asymptomatic Patients With Chronic Severe Aortic Regurgitation and Left Ventricular Dysfunction

Cellular Response of Human Cardiac Fibroblasts to Mechanically Simulated Aortic Regurgitation

Myocardial fibrosis has been identified in biopsy specimens from catheterization and valve replacement surgery in patients with severe chronic aortic regurgitation (AR). While characterization of these extracellular matrix (ECM) alterations has been incomplete in humans, fibrosis also has been identified in chronic severe experimentally created AR, in which ECM composition features abnormal fibronectin/glycoprotein production, with normal collagen content. Virtually identical ECM variations have been induced when normal rabbit cardiac fibroblasts (CF) are subjected in culture to cyclic mechanical strain mimicking that found in the left ventricle (LV) in severe AR. To determine whether the changes seen experimentally can be extrapolated to humans, we exposed normal human CF in culture to the mechanical strain employed in the experimental model to simulate severe AR (n=3 replications from 1 patient). CF were isolated from epicardial biopsy distant from diseased coronary arteries in a 38-year-old man with normal LV function and without prior myocardial infarction who was undergoing elective coronary artery bypass grafting. Gelatin Sepharose affinity chromatography (GSAC) and Western analysis were used to compare fibronectin expression in strained versus nonstrained normal human CF in tissue culture; Western analysis was used to compare type I collagen production. In AR-strained CF, fibronectin synthesis nominally increased [av 38% (Western) and 45% (GSAC)] relative to control; type I collagen synthesis was virtually unchanged. These results simulate those found experimentally and suggest that human CF, like rabbit CF, manifest abnormal compositional distribution of ECM proteins in AR.

Thallium-201 single-photon emission computed tomography: Quantitative assessment of left ventricular perfusion and structural change in patients with chronic aortic regurgitation

Previously, perfusion defect in the left ventricle was detected by thallium-201 (201T1) single-photon emission computed tomography (SPECT) in aortic regurgitation (AR). The significance of 201T1 SPECT, however, has not been clarified. Limited information is available regarding the relationship between functional characteristics and scintigraphic findings. The purpose of this study was to elucidate the role of exercise 201T1 SPECT in assessing myocardial perfusion or structural change in chronic AR. We examined the correlation between 201T1 scintigraphic findings and left ventricular (LV) function parameters in 11 patients. Defect volume ratio (DVR) in exercise 201T1 SPECT was used as a parameter of the range of abnormal thallium distribution. Left ventricular parameters were obtained by right and retrograde left cardiac catheterizations. The relationship between DVR and the parameters was analyzed. The DVR ranged from 1.0 to 28.3% (average 12.1 + 8.5 %). There was a significant correlation (r = 0.77, p < 0.05) between DVR and end-diastolic volume index (EDVI), a definite correlation (r = 0.66, p < 0.01) between DVR and end-systolic volume index (ESVI), and a good correlation (r = -0.77, p <0.05) between DVR and end-systolic wall stress (ESS)/ ESVI; however, no such correlation was found between DVR and ejection fraction. All patients showed abnormal defects in 201T1 accumulation scattered across the entire ventricle. A strong correlation between DVR and ESS/ESVI, an index of myocardial contractility, was a major finding of this study, suggesting a significant association between abnormal myocardial perfusion or structural alteration and reduction in myocardial contractility in chronic AR.

An echocardiographic index for decompensation of the chronically volume-overloaded left ventricle in children

The criterions for the timing of surgical intervention in children with rheumatic mitral or aortic valvar regurgitation are not defined. I hypothesized that, in children with chronic mitral or aortic regurgitation, an index for decompensation could be created by using the ratio of the diastolic left ventricular wall thickness to the radius, and that such an index could prove useful in determining the optimal time for surgical intervention. The left ventricular echocardiograms were obtained at the tips of the leaflets of the mitral valve by M-mode echocardiography. The diastolic septal wall thickness was measured between the right and left ventricular endocardial layers, and the posterior wall thickness between the endocardium and the interphase between the epicardium and the myocardium. The left ventricular diastolic dimension was then measured, between the posterior and septal wall endocardial layers, and systolic dimension as the smallest distance detected between these layers. All diastolic measurements were made at the time of the R wave of electrocardiogram, using the leading edge technique. The ratio of wall thickness was measured using the mean of septal and posterior wall thicknesses divided by half the diastolic dimensions, the normalized thickness of the wall previously referred to as the h/r ratio and relative mural thickness. The ratio of wall thickness to left ventricular radius, and its relation to systolic left ventricular pressure or systolic blood pressure, was found to be linear in 89 normal school children, and 39 children with aortic stenosis. For future predictions, I calculated the 95th percentile limits and the 95th percentile confidence bands for this relation. Using the same data, it proved possible to calculate ratios of wall thickness for various ranges of either systolic blood pressure or left ventricular peak pressure. By using the normal limits of 0.356 plus or minus 0.0316 of the ratio, appropriate for the systolic blood pressure of children with mitral regurgitation, I determined the adequacy of the ratio of wall thickness. Of the children, 51 were in ventricular failure, and these had an inadequate ratio, below two standard deviation. Of the others, 21 had an inadequate ratio to within minus one to minus two standard deviations, and 12 of these were asymptomatic, 8 were symptomatic, but only one was in ventricular failure. For 18 children with aortic regurgitation, using the same limits, one child was within 1 standard deviation and was asymptomatic, 8 fell within minus 1 to minus 2 standard deviations and 2 of these were symptomatic, 5 were in ventricular failure, and 1 was asymptomatic, while the other 9 had ratios falling less than minus 2 standard deviations, and all were in ventricular failure. I conclude that the index of normalized wall thickness defined as the ratio of the left ventricular wall thickness to its radius is adequate, and within normal limits, when there is compensated volume overload, but is inadequate and below normal limits when the volume overloaded left ventricle becomes decompensated. My data suggests that the persistently decreasing ratio of wall thickness below the limits of normality serves as an indicator of ventricular decompensation, and thus can be used as a new criterion for determining the optimal time for surgical intervention.

Prognostic Impact of Systolic Hypertension on Asymptomatic Patients With Chronic Severe Aortic Regurgitation and Initially Normal Left Ventricular Performance at Rest

The influence of systolic hypertension (SH) on the natural history of chronic aortic regurgitation (AR) and the clinical effect of antihypertensive medication on patients who have hypertension and AR are incompletely defined. Therefore, we reviewed the clinical course of 80 unoperated patients who were entered prospectively into an assessment of natural history of AR and its predictors and were asymptomatic with normal left ventricular ejection fraction (LVEF) at rest at study entry; 30 of 80 patients had SH (systolic blood pressure >140 mm Hg); 20 of 80 patients (16 had SH) used antihypertensive drugs for the long term (not mandated by protocol). During an average 7.2-year event-free follow-up, 24 patients developed symptoms alone (n = 14), subnormal LVEF with or without symptoms (n = 8), or died suddenly (n = 2). SH tripled the average annual risk of cardiac events (8.47% vs 2.85%, p = 0.004). The effect of systolic blood pressure was independent of age, gender, diastolic blood pressure, LV diastolic dimension, fractional shortening, and LVEF at rest (p = 0.004 to <0.008). However, positive prognostic interactions existed between systolic blood pressure and pulse pressure (p <0.001), LVEF during exercise (p <0.001), change in LVEF from rest to exercise (p <0.001), and the contractility index (p <0.02). Among patients who had SH, antihypertensive therapy predicted increased event risk (average annual risk 15.46% vs 3.98%, p <0.02) and remained predictive when analysis was adjusted for potentially confounding subgroup variations at study entry (p <0.03, all models). In conclusion, SH portends poor clinical outcome in chronic severe AR. As a group, antihypertensive drugs do not mitigate outcome, although the effect of individual drugs is uncertain and at least some may be deleterious. The theoretically based practice of giving antihypertensive drugs to patients who have AR requires reexamination.

Long-Term Survival and Functional Results After Aortic Valve Replacement in Asymptomatic Patients With Chronic Severe Aortic Regurgitation and Left Ventricular Dysfunction

Long-Term Survival and Functional Results After Aortic Valve Replacement in Asymptomatic Patients With Chronic Severe Aortic Regurgitation and Left Ventricular Dysfunction

Are patients with isolated chronic aortic regurgitation operated in time? Analysis of survival data over a decade

Patients suffering from chronic isolated aortic regurgitation have a less favorable outcome than patients with aortic stenosis. According to international recommendations, these patients should undergo surgery as soon as left ventricular function begins to deteriorate, that is, surgery is not to be postponed until clinical symptoms become relevant. The study was undertaken to evaluate how satisfactory our timing of surgery was, as reflected by survival data. Survival was studied retrospectively in a consecutive series of patients undergoing surgery for chronic isolated aortic regurgitation during a 10-year period in our institution. Results were compared with data from the literature. By excluding patients with aortic aneurysms and acute endocarditis, we formed a homogeneous patient group of 88 subjects. Thirty-day mortality was 1% and late mortality after a mean follow-up period of 6 years was 11%. Compared with survival data from an earlier study in which the patient population was similar and resided in the same geographic area, the results in our patient group seem to be better. It is noteworthy that despite a strong effort to recommend surgery at an earlier stage of the disease than previously, 35% of the patients had moderate or severe left ventricular dysfunction preoperatively because of late referrals. This stresses the importance of early detection and careful preoperative follow-up with noninvasive methods in patients with aortic regurgitation.

Brain Natriuretic Peptide and the Severity of Aortic Regurgitation: Is There Any Correlation?

We aimed to evaluate the correlation between aortic regurgitation severity and brain natriuretic (BNP) levels as a marker for left ventricular dysfunction. Sixty consecutive male patients (mean age 22 +/- 3 years) with isolated chronic aortic regurgitation were enrolled in the study together with a control group of 30 age-matched healthy volunteers (group A). Patients were classified with regard to aortic regurgitation vena contracta width as follows: group B, < 3 mm, mild (n = 16); group C, > or = 3 and < 6 mm, moderate (n = 26); group D, > or = 6 mm, severe (n = 18). BNP measurements were performed with a fluorescence immunoassay kit. BNP levels were increased in patients with aortic regurgitation, and severity of regurgitation had a significant influence on BNP levels. This effect can be explained by the volume loading effect of aortic regurgitation.