Etiology impacts survival in patients with severe aortic regurgitation: results from a cohort of 756 patients.

BACKGROUND AND AIM OF THE STUDY: Severe aortic regurgitation (AR) is caused by a variety of mechanisms, which include the degenerative process, bicuspid aortic valve (BAV), aortic root dilation, endocarditis or a combination of these. Their frequency in a contemporary clinical series, and their impact on survival, are currently unknown. METHODS: The authors' echocardiographic database between 1993 and 2007 was screened for patients with severe AR, and yielded 756 patients. Detailed chart reviews were performed to acquire clinical and demographic data. Mortality data were obtained from the social security death index and analyzed as a function of the condition's etiology. RESULTS: The probable etiologies for AR were: degenerative in 29% of patients, BAV in 10%, aortic root pathology in 11%, endocarditis in 10%, and mixed or unclear mechanism in 40%. Survival was a function of the etiology (p < 0.0001), with degenerative mechanism having the worst prognosis and BAV the best. This differential impact on mortality remained significant after adjusting for age, gender, coronary artery disease, diabetes mellitus, renal insufficiency, left ventricular ejection fraction and aortic valve replacement, using the Cox regression model (p < 0.0001). CONCLUSION: Etiology has a significant independent impact on mortality in patients with severe AR, with the worst survival being seen in degenerative AR.

Slow rate of progression of grade 1 and 2+ aortic regurgitation.

BACKGROUND AND AIM OF THE STUDY: Although the progression of aortic stenosis has been well studied, the rate of progression of aortic regurgitation (AR) has not been definitively established. Further data would be valuable for clinical decision-making in patients with milder degrees of AR undergoing non-aortic valve cardiac surgery. Hence, this point was investigated in a large cohort of patients with grade 1 or 2+ AR. METHODS: The authors' echocardiographic database acquired between 1993 and 2007 was screened for patients with grade 1 or 2+ AR who had undergone follow up echocardiography at least one year later. The AR severity was graded as 1 to 4+, and any annual changes in AR grade were monitored. RESULTS: Among a total of 4,128 patients identified, 3,266 had grade 1+ AR and 862 had grade 2+ AR on the initial echocardiogram: the mean age was 67 +/- 15 years, and the duration of follow up was 4.2 +/- 2.7 years. Of those patients initially with grade 1+ AR, 95% showed no change in AR over a mean interval of 4.2 years, with an annual average increase in AR grade of 0.04. Of those patients initially with grade 2+ AR, 90% showed no change over this period, with an annual average increase in grade of 0.07. In the entire cohort, the AR progression correlated positively with age (p = 0.03), ventricular septal thickness (p < 0.0001), stroke distance (the time velocity integral of flow in the left ventricular outflow tract) (p = 0.0003), the presence of any degree of aortic stenosis (p = 0.01), and initial AR severity (p < 0.0001). CONCLUSION: The rate of AR progression is extremely slow, and prophylactic aortic valve replacement during non-aortic surgery may not be indicated in patients with grade 1 or 2+ AR in the absence of any higher risk for progression, such as grade 2+ AR combined with any degree of aortic stenosis and advanced age.

Survival in patients with severe aortic regurgitation and severe left ventricular dysfunction is improved by aortic valve replacement: results from a cohort of 166 patients with an ejection fraction < or =35%.

BACKGROUND: Aortic valve replacement (AVR) in patients with severe aortic regurgitation (AR) and left ventricular (LV) dysfunction entails a higher surgical risk. Though it may improve symptoms and LV size, it is not known whether it translates into a survival benefit. METHODS AND RESULTS: This retrospective cohort study included patients screened from our echocardiographic database between 1993 and 2007 for patients with severe AR and LV ejection fraction (EF) < or =35%. Charts reviews were conducted for clinical, pharmacological, and surgical information. Mortality data were obtained from the social security death index and analyzed as a function of AVR adjusted for the propensity score. Of the 785 patients with severe AR, 166 patients had severe LV dysfunction defined as an EF < or =35%: 69% of these were men, age 65+/-16 years, and LV EF was 23+/-8%. Kaplan-Meier analysis revealed that performance of AVR (n=53) was associated with a better survival (P=0.001). Adjusted for the propensity score, AVR was associated with a significantly lower mortality hazard (HR 0.59, CI 0.42 to 0.98, P=0.04). CONCLUSIONS: There is a clear reluctance to offer AVR in a large number of patients with severe AR associated with LV dysfunction. However, the performance of AVR in these patients is associated with a mortality benefit supporting the current ACC/AHA guidelines.

Cisplatin-Induced Renal Salt Wasting Requiring over 12 Liters of 3% Saline Replacement.

Cisplatin is known to induce Fanconi syndrome and renal salt wasting (RSW). RSW typically only requires transient normal saline (NS) support. We report a severe RSW case that required 12 liters of 3% saline. A 57-year-old woman with limited stage small cell cancer was admitted for cisplatin (80 mg/m2) and etoposide (100 mg/m2) therapy. Patient's serum sodium (SNa) decreased from 138 to 133 and 125 mEq/L within 24 and 48 hours of cisplatin therapy, respectively. A diagnosis of syndrome of inappropriate antidiuretic hormone secretion (SIADH) was initially made. Despite free water restriction, patient's SNa continued to decrease in association with acute onset of headaches, nausea, and dizziness. Three percent saline (3%S) infusion with rates up to 1400 mL/day was required to correct and maintain SNa at 135 mEq/L. Studies to evaluate Fanconi syndrome revealed hypophosphatemia and glucosuria in the absence of serum hyperglycemia. The natriuresis slowed down by 2.5 weeks, but 3%S support was continued for a total volume of 12 liters over 3.5 weeks. Attempts of questionable benefits to slow down glomerular filtration included the administration of ibuprofen and benazepril. To our knowledge, this is the most severe case of RSW ever reported with cisplatin.

Survival benefit of aortic valve replacement in older patients with asymptomatic chronic severe aortic regurgitation.

BACKGROUND: According to American College of Cardiology/American Heart Association guidelines, isolated aortic valve replacement (AVR) is a class III indication for patients with asymptomatic chronic severe aortic regurgitation (AR), left ventricular (LV) ejection fraction (EF) greater than 50%, LV end-diastolic dimension less than 70 mm, and LV end-systolic dimension less than 50 mm. METHODS: We screened our echocardiographic database for all chronic severe AR patients between 1993 and 2007. Chart reviews were performed to collect clinical, demographic, and pharmacological data. Mortality was analyzed as a function of AVR. RESULTS: In all, 123 patients were found to have chronic severe asymptomatic AR; they had a mean age of 60 +/- 17 years and mean LVEF of 60% +/- 15%. A subgroup of 79 patients was found to have asymptomatic severe AR with an LVEF greater than 50%, LV end-diastolic dimension less than 70 mm, and LV end-systolic dimension less than 50 mm. By Kaplan-Meier analysis, patients not undergoing AVR had 1-, 5-, and 10-year survival rates of 86%, 71%, and 46%, respectively, compared with 100%, 94%, and 94%, respectively, for patients who underwent AVR (p = 0.004). Aortic valve replacement remained an independent predictor of increased survival after adjusting for group differences and univariate predictors of mortality. The benefit of AVR was further supported by propensity score analysis. CONCLUSIONS: Despite serving as a class III indication, AVR is independently associated with increased survival among patients with severe asymptomatic AR, LVEF greater than 50%, LV end-diastolic dimension less than 70 mm, and LV end-systolic dimension less than 50 mm.

Survival benefit of aortic valve replacement in patients with severe aortic regurgitation and pulmonary hypertension.

BACKGROUND: Severe pulmonary hypertension occurs in approximately 10% of patients with severe aortic regurgitation (AR). The potential survival benefit of aortic valve replacement (AVR) in these patients is not known, and was analyzed in a large cohort of patients. METHODS: Our echocardiographic data was screened for severe AR patients with severe pulmonary hypertension defined as pulmonary artery systolic pressure of 60 mm Hg or greater. Chart reviews were performed for clinical, pharmacologic, and surgical details, and survival data were analyzed as a function of AVR. RESULTS: Of the 506 patients with severe AR and measurable pulmonary artery pressures by echocardiography, 83 had severe pulmonary hypertension defined as a pulmonary artery systolic pressure of 60 mm Hg or greater. Severe pulmonary hypertension was associated with lower left ventricular ejection fraction (47% +/- 22% versus 53% +/- 19%, p = 0.006), larger left ventricular size (p = 0.03), and higher grades of mitral regurgitation (2.7 +/- 1.2 versus 1.7 +/- 1.1, p < 0.0001). Of the 83 patients with severe pulmonary hypertension, 32 underwent AVR, which was associated with better survival compared with patients who did not (1-year survival 90% versus 58% and 5-year survival 62% versus 22%, respectively; p = 0.004). After adjusting for comorbidities, AVR remained an independent predictor of better survival (hazard ratio 0.45, 95% confidence interval: 0.22 to 0.92, p = 0.03). This survival benefit of AVR was further supported by propensity score analysis. CONCLUSIONS: Severe pulmonary hypertension occurs in approximately 16% of patients with severe AR and is associated with left ventricular enlargement with dysfunction and resultant mitral regurgitation. Aortic valve replacement is associated with an independent survival benefit in these patients.

Effect of beta-blocker therapy on survival in patients with severe aortic regurgitation results from a cohort of 756 patients.

OBJECTIVES: We sought to investigate the effect of beta-blocker (BB) therapy on survival in patients with severe aortic regurgitation (AR). BACKGROUND: Beta-blockers are thought to be contraindicated in patients with AR because a slower heart rate increases the duration of diastole during which AR occurs. But AR also causes neuroendocrine activation similar to a heart failure state for which BBs are potentially beneficial. METHODS: This is an observational study. Our echocardiographic database was screened for patients with severe AR. Detailed chart reviews were performed for clinical, demographic, and therapeutic data. Mortality data were obtained from the Social Security Death Index and analyzed as a function of BB therapy. RESULTS: Three hundred fifty-five (47%) of the 756 patients with severe AR were on a BB; mean age 61 +/- 18 years and ejection fraction was 54 +/- 19%. Over a mean follow-up of 4.5 years, BB therapy was associated with a higher survival rate (1- and 5-year survival rates of 90% and 70%, respectively) compared with those without (1- and 5-year survival rates of 75% and 55%, respectively) (p = 0.0009). The Cox regression model showed that BB therapy was an independent predictor of better survival after adjusting for age, sex, heart rate, hypertension, coronary artery disease, diabetes mellitus, heart failure, renal insufficiency, ejection fraction, and aortic valve replacement (hazard ratio: 0.74, 95% confidence interval: 0.58 to 0.93, p = 0.01). The survival benefit of BB therapy was further supported by propensity score analysis. CONCLUSIONS: This observational study strongly suggests that BB therapy is associated with a survival benefit in patients with severe AR.

Risk factors for progression of calcific aortic stenosis and potential therapeutic targets.

Current thought regarding the progression of calcific aortic stenosis (AS) is presented. After summarizing contemporary ideas about AS pathogenesis, the present article examines the factors that may affect disease progression. Data indicate that this process may be accelerated by aortic valve structure, degree of valvular calcification, chronic renal insufficiency and cardiovascular risk factors such as diabetes and dyslipidemia. Finally, the present review discusses potential therapeutic targets to slow AS progression.