Padmini Varadarajan

Survival Benefit of Aortic Valve Replacement in Patients With Severe Aortic Stenosis With Low Ejection Fraction And Low Gradient With Normal Ejection Fraction

BACKGROUND Aortic stenosis (AS) is becoming increasingly common with the aging population. Many of these patients have reduced left ventricular (LV) ejection fractions (EF) or low transvalvular gradients resulting in reluctance to offer aortic valve replacement (AVR). METHODS Our echocardiographic database for the period of 1993 to 2003 was screened for severe AS (aortic valve area [AVA] </= 0.8 cm(2)) with LVEF 0.35 or less or a mean transvalvular gradient of 30 mm Hg or less. Chart reviews were performed for clinical, pharmacologic, and surgical details. Survival data were obtained from the Social Security Death Index and analysis was performed using Kaplan-Meier, Cox regression, sensitivity, and propensity score analysis. RESULTS Of the 740 patients with severe AS, 194 (26%) had severe LV dysfunction defined as EF 0.35 or less and 168 (23%) a mean transvalvular gradient of 30 mm Hg or less. Low ejection fraction was not a prerequisite for a low gradient. The Univariate predictors of higher mortality in both groups included higher age, lower ejection fraction, renal insufficiency, and lack of aortic valve replacement. Lack of aortic valve replacement was a strong predictor of mortality after adjusting for 18 clinical, echocardiographic, and pharmacologic variables. There were 72 patients with EF 0.20 or less, of whom 18 had AVR, which was associated with a large survival benefit similar to the entire cohort. In the 52 patients with EF 0.55 or less and mean gradient less than 30 mm Hg, the 5-year survival with AVR was 90% compared with 20% without AVR (p < 0.0001) which was supported by propensity score analysis as well. CONCLUSIONS Severe LV dysfunction or a low transvalvular gradient is seen in about a quarter of patients with severe AS and there is a reluctance to offer AVR in these patients. Aortic valve replacement is associated with a large mortality 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.

Effect of Beta-Blocker Therapy on Survival in Patients With Severe Mitral Regurgitation and Normal Left Ventricular Ejection Fraction

Chronic volume overload from chronic severe mitral regurgitation (MR) results in neuroendocrine activation similar to the heart failure syndrome despite normal left ventricular (LV) ejection fraction (EF). Hence, the hypothesis that beta-blocker (BB) therapy may have a beneficial effect in these patients was tested using a large observational cohort. Our echocardiographic database was searched for patients with severe MR and normal LVEF. Full chart reviews were conducted for clinical and pharmacologic data. Survival was analyzed as a function of BB therapy. The search produced 895 patients aged 68 +/- 17 years, 44% men, with LVEF 66 +/- 7%. Of these, 32% were on BB therapy. Use of a BB was associated with a significantly decreased mortality hazard of 0.62 (95% confidence interval 0.46 to 0.83, p = 0.002), which was unchanged after adjusting for age, gender, LVEF, coronary artery disease, diabetes mellitus, hypertension, and cardiac valve surgery. The independent beneficial effect of BBs was seen in patients with or without coronary artery disease, those with or without hypertension, and patients managed both medically and surgically. In conclusion, use of BB therapy was associated with a significant independent survival benefit in patients with chronic severe MR with normal LVEF. This benefit was seen in patients with or without coronary artery disease, as well as patients managed both medically and surgically. Use of BBs in patients with severe MR despite normal LVEF is suggested.

Arterial Spin Labeled CMR Detects Clinically Relevant Increase in Myocardial Blood Flow With Vasodilation

OBJECTIVES This study sought to determine whether arterial spin labeled (ASL) cardiac magnetic resonance (CMR) is capable of detecting clinically relevant increases in regional myocardial blood flow (MBF) with vasodilator stress testing in human myocardium. BACKGROUND Measurements of regional myocardial perfusion at rest and during vasodilatation are used to determine perfusion reserve, which indicates the presence and distribution of myocardial ischemia. ASL CMR is a perfusion imaging technique that does not require any contrast agents, and is therefore safe for use in patients with end-stage renal disease, and capable of repeated or continuous measurement. METHODS Myocardial ASL scans at rest and during adenosine infusion were incorporated into a routine CMR adenosine induced vasodilator stress protocol and was performed in 29 patients. Patients who were suspected of having ischemic heart disease based on first-pass imaging also underwent x-ray angiography. Myocardial ASL was performed using double-gated flow-sensitive alternating inversion recovery tagging and balanced steady-state free precession imaging at 3-T. RESULTS Sixteen patients were found to be normal and 13 patients were found to have visible perfusion defect based on first-pass CMR using intravenous gadolinium chelate. In the normal subjects, there was a statistically significant difference between MBF measured by ASL during adenosine infusion (3.67 ± 1.36 ml/g/min), compared to at rest (0.97 ± 0.64 ml/g/min), with p < 0.0001. There was also a statistically significant difference in perfusion reserve (MBF(stress)/MBF(rest)) between normal myocardial segments (3.18 ± 1.54) and the most ischemic segments in the patients with coronary artery disease identified by x-ray angiography (1.44 ± 0.97), with p = 0.0011. CONCLUSIONS This study indicates that myocardial ASL is capable of detecting clinically relevant increases in MBF with vasodilatation and has the potential to identify myocardial ischemia.

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.

Myocardial viability and impact of surgical ventricular reconstruction on outcomes of patients with severe left ventricular dysfunction undergoing coronary artery bypass surgery: Results of the Surgical Treatment for Ischemic Heart Failure trial

OBJECTIVES In the Surgical Treatment for Ischemic Heart Failure trial, surgical ventricular reconstruction plus coronary artery bypass surgery was not associated with a reduction in the rate of death or cardiac hospitalization compared with bypass alone. We hypothesized that the absence of viable myocardium identifies patients with coronary artery disease and left ventricular dysfunction who have a greater benefit with coronary artery bypass graft surgery and surgical ventricular reconstruction compared with bypass alone. METHODS Myocardial viability was assessed by single photon computed tomography in 267 of the 1000 patients randomized to bypass or bypass plus surgical ventricular reconstruction in the Surgical Treatment for Ischemic Heart Failure. Myocardial viability was assessed on a per patient basis and regionally according to prespecified criteria. RESULTS At 3 years, there was no difference in mortality or the combined outcome of death or cardiac hospitalization between those with and without viability, and there was no significant interaction between the type of surgery and the global viability status with respect to mortality or death plus cardiac hospitalization. Furthermore, there was no difference in mortality or death plus cardiac hospitalization between those with and without anterior wall or apical scar, and no significant interaction between the presence of scar in these regions and the type of surgery with respect to mortality. CONCLUSIONS In patients with coronary artery disease and severe regional left ventricular dysfunction, assessment of myocardial viability does not identify patients who will derive a mortality benefit from adding surgical ventricular reconstruction to coronary artery bypass graft surgery.

Beta and Angiotensin Blockades Are Associated With Improved 10-Year Survival in Renal Transplant Recipients

Background Mortality in allograft kidney transplant recipients is high, and cardiovascular disease is the leading cause of death in these patients. They have heightened activity of sympathetic and renin–angiotensin systems. We tested the hypothesis that blockade of sympathetic and renin–angiotensin systems in these patients may offer a survival benefit using a large cohort of patients with long‐term follow up. Methods and Results Medical records of 321 consecutive patients from our institution who had received renal transplantation between 1995 and 2003 were abstracted. Survival was analyzed as a function of pharmacological therapies adjusted for age, sex, and comorbidities. The characteristics of the 321 patients were as follows: age at transplant, 44±13 years; 40% male; 89% with hypertension; 36% with diabetes, and mean left ventricular ejection fraction of 60%. Over a follow‐up of 10±4 years, there were 119 deaths. Adjusted for age, sex, diabetes, and coronary artery disease, use of a beta‐blocker therapy (P=0.04) and angiotensin‐converting enzyme inhibitor or receptor blocker (P=0.03) was associated with better survival. This treatment effect was seen across all major clinical subgroups and was supported by propensity score analysis. The propensity score–adjusted 10‐year survival was 95% in those taking both groups of medications, 72% in those taking either of them, and 64% in those taking neither (P=0.004). Conclusions Use of beta‐blocker and angiotensin blocking therapies is associated with higher survival after renal transplantation, indicating their potential protective role in this high‐risk population.

Prognostic implications of tricuspid regurgitation in patients with severe aortic regurgitation: results from a cohort of 756 patients

Tricuspid regurgitation (TR) is common, but neglected. We evaluated the prognostic implications of TR in a cohort of 756 patients with severe aortic regurgitation (AR). A cohort of 756 patients with AR was identified from our echocardiographic database. Chart reviews were performed. Survival as a function of TR severity was analysed. Of the 756 patients with severe AR, 264 (35%) had ≥ 2+ TR. Univariate correlates of TR were older age (P < 0.0001), female gender (P < 0.0001), lower left ventricular ejection fraction (P < 0.0001), atrial fibrillation (P < 0.0001), presence of a pacemaker (P < 0.0001), higher PASP (P < 0.0001), presence of 3 or 4+ mitral regurgitation (P < 0.0001) and not being on a beta-blocker (P < 0.0001) or statins (P = 0.007). After adjusting for group differences, ≥ 2+ TR was an independent predictor of higher mortality (RR 1.47, P = 0.005). Aortic valve replacement (AVR) was independently associated with improved survival in patients with ≥ 2+ TR. (RR 0.46, 95% CI 0.36-0.60, P < 0.0001). In conclusion, in severe AR patients, ≥ 2+ TR is independently associated with a higher mortality. The performance of AVR in these patients with ≥ 2+ TR is associated with a survival benefit. Development of ≥ 2+ TR in these patients is a marker of decompensation and should serve as an indication for AVR.

Echocardiographic evaluation of patent foramen ovale and atrial septal defect.

Patent foramen ovale (PFO) is a common variant present in up to 25% of the population. Atrial septal defect (ASD) is a direct communication between the 2 atrial chambers, of which the ostium secundum variety is the most common. This manuscript is an in depth review of the complex atrial septation, the diagnosis of PFO and ASD and its clinical and therapeutic implications.

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.