Jyothy Puthumana

Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy: Insights From Wall Shear Stress Mapping

BACKGROUND Suspected genetic causes for extracellular matrix (ECM) dysregulation in the ascending aorta in patients with bicuspid aortic valves (BAV) have influenced strategies and thresholds for surgical resection of BAV aortopathy. Using 4-dimensional (4D) flow cardiac magnetic resonance imaging (CMR), we have documented increased regional wall shear stress (WSS) in the ascending aorta of BAV patients. OBJECTIVES This study assessed the relationship between WSS and regional aortic tissue remodeling in BAV patients to determine the influence of regional WSS on the expression of ECM dysregulation. METHODS BAV patients (n = 20) undergoing ascending aortic resection underwent pre-operative 4D flow CMR to regionally map WSS. Paired aortic wall samples (i.e., within-patient samples obtained from regions of elevated and normal WSS) were collected and compared for medial elastin degeneration by histology and ECM regulation by protein expression. RESULTS Regions of increased WSS showed greater medial elastin degradation compared to adjacent areas with normal WSS: decreased total elastin (p = 0.01) with thinner fibers (p = 0.00007) that were farther apart (p = 0.001). Multiplex protein analyses of ECM regulatory molecules revealed an increase in transforming growth factor β-1 (p = 0.04), matrix metalloproteinase (MMP)-1 (p = 0.03), MMP-2 (p = 0.06), MMP-3 (p = 0.02), and tissue inhibitor of metalloproteinase-1 (p = 0.04) in elevated WSS regions, indicating ECM dysregulation in regions of high WSS. CONCLUSIONS Regions of increased WSS correspond with ECM dysregulation and elastic fiber degeneration in the ascending aorta of BAV patients, implicating valve-related hemodynamics as a contributing factor in the development of aortopathy. Further study to validate the use of 4D flow CMR as a noninvasive biomarker of disease progression and its ability to individualize resection strategies is warranted.

Global longitudinal strain aids the detection of non-obstructive coronary artery disease in the resting echocardiogram.

AIMS To evaluate the diagnostic power of abnormal global longitudinal strain (GLS) to detect non-obstructive coronary artery disease (CAD) in the resting echocardiogram. GLS using two-dimensional speckle-tracking echocardiography (2D STE) is a powerful tool for detecting advanced CAD. However, the diagnostic power of 2D STE for detecting moderate, clinically unapparent CAD from images obtained at rest is unknown. METHODS AND RESULTS We retrospectively studied 2D STE characteristics in 123 consecutive patients who underwent stress echocardiography, and subsequently coronary angiography within 10 days. We compared the diagnostic power of GLS at rest to the conventional wall motion score index (WMSI) during stress for detecting stenosis ≥ 50% (CAD(>50)) in any major coronary artery. Studies with akinetic or dyskinetic segments and reduced left ventricular ejection fraction were excluded. In 56 patients with significant CAD(>50), GLS was -16.77 ± 3.18% compared with -19.05 ± 3.43% in the 67 patients without CAD(<50) (P = 0.0002). A GLS cutpoint of greater than -17.77% had the most optimal sensitivity and specificity (66/76%) for detecting CAD and was comparable to a WMSI ≥ 1.13 (68/70%) measured during stress. CONCLUSION Non-obstructive CAD was identified by a reduced GLS measured by 2D STE in rest images with similar accuracy to the traditional WMSI measured in stress echocardiography.

Incremental Prognostic Value of Stress Echocardiography Over Clinical and Stress Electrocardiographic Variables in Patients With Prior Myocardial Infarction: “Warranty Time” of a Normal Stress Echocardiogram

Background: Patients with prior myocardial infarction (MI) are at increased risk of subsequent cardiac events (MI or cardiac death). The incremental prognostic value and warranty time of a normal stress echocardiogram in this high‐risk population is not well defined. Methods: We evaluated 251 consecutive patients (62 ± 11 years; 64% males) with remote history of MI (>6 weeks) undergoing stress echocardiography (83% dobutamine). Ischemia was defined as a new reversible wall motion abnormality and/or biphasic response. Follow‐up for up to 4 years (mean 2.9 ± 1.0 years) for confirmed MI (n = 7) and cardiac death (n = 15) were obtained. Results: Stress echocardiography effectively risk stratified patients into normal versus abnormal subgroups (Event rate 0.8% per year vs 4.2% per year; P = 0.01; RR = 5.6, 95% CI = 1.3–24.7). In patients with a normal stress echocardiogram, the event rate at the end of 6, 12, and 18 months were <1% per year. After 18 months the event rate in patients with a normal stress echocardiogram increased greatly (>1% per year). Stress echocardiography yields incremental prognostic value over clinical and stress electrocardiographic variables (Global chi‐square increased from 12.4 to 25 to 31.1, P < 0.0001 both groups). Conclusions: Stress echocardiography yields appropriate risk stratification and prognosis and provides incremental prognostic value over clinical and stress electrocardiographic variables even in patients with prior MI. A normal stress echocardiogram portends a benign prognosis (<1% event rate/year) for up to 18 months.

Comparison of outcomes and presentation in men-versus-women with bicuspid aortic valves undergoing aortic valve replacement.

Gender disparities in short- and long-term outcomes have been documented in cardiac and valvular heart surgery. However, there is a paucity of data regarding these differences in the bicuspid aortic valve (BAV) population. The aim of this study was to examine gender-specific differences in short- and long-term outcomes after surgical aortic valve (AV) replacement in patients with BAV. A retrospective analysis was performed in 628 consecutive patients with BAV who underwent AV surgery from April 2004 to December 2013. To reduce bias when comparing outcomes by gender, propensity score matching obtained on the basis of potential confounders was used. Women with BAV who underwent AV surgery presented with more advanced age (mean 60.7 ± 13.8 vs 56.3 ± 13.6 years, p <0.001) and less aortic regurgitation (29% vs 44%, p <0.001) and had a higher risk for in-hospital mortality (mean Ambler score 3.4 ± 4.4 vs 2.5 ± 4.0, p = 0.015). After propensity score matching, women received more blood products postoperatively (48% vs 34%, p = 0.028) and had more prolonged postoperative lengths of stay (median 5 days [interquartile range 5 to 7] vs 5 days [interquartile range 4 to 6], p = 0.027). Operative, discharge, and 30-day mortality and overall survival were not significantly different. In conclusion, women with BAV who underwent AV surgery were older, presented with less aortic regurgitation, and had increased co-morbidities, lending higher operative risk. Although women received more blood products and had significantly longer lengths of stay, short- and long-term outcomes were similar.

Effect of cardiac resynchronization therapy on right ventricular function.

Purpose of review The focus only on the left ventricle (LV) for both evaluation of cardiac dyssynchrony and the efficacy of resynchronization therapy (CRT) is too limited to explain the nuances of clinical response to CRT. Right ventricular function, synchrony and remodeling are now commonly characterized noninvasively. This review presents new insights into the role of the right ventricle independently and in conjunction with the LV in determining the clinical efficacy of CRT. Recent findings There are patients with predominantly right ventricular dyssynchrony who respond to CRT without reverse remodeling of the LV. Studies of longitudinal axis function of the right ventricle show that contractile function improvement precedes right ventricular reverse remodeling in clinical responders to CRT. The discordance seen in some CRT responders between improvements in left ventricular and right ventricular morphology, function and markers of synchrony is best understood using multiple markers of cardiac longitudinal axis function and cardiac deformation analysis. Summary Advanced right ventricular dysfunction reduces the likelihood of clinical response to CRT. However, right ventricular contractile function may improve following CRT independent of changes in right ventricular size or volumetric measures of right ventricular function. The consequences of isolated improvements in right ventricular function on CRT-related prognosis deserve further study.

Effect of aortic aneurysm replacement on outcomes after bicuspid aortic valve surgery: Validation of contemporary guidelines

OBJECTIVE Bicuspid aortic valve (BAV) disease is associated with aortic dilatation and aneurysm (AN) formation. The American College of Cardiology/American Heart Association (ACC/AHA) 2006 guidelines recommend replacement of the ascending aorta for an aortic diameter (AD)> 45 mm in patients undergoing aortic valve replacement (AVR). We evaluated the outcomes of AVR and AVR with aortic replacement (AVR/AN). METHODS We retrospectively reviewed (2004-2011) the data from 456 patients with BAV and compared the morbidity and mortality between the AVR and AVR/AN groups and 3 subgroups: AVR with an AD<45 mm; AVR/AN with an AD of 45 to 49 mm; and AVR/AN with an AD of ≥50 mm. Propensity score matching was used to reduce bias. RESULTS Of the 456 patients, 250 (55%) underwent AVR and 206 (45%) AVR/AN, with 98% compliance with the current guidelines. The overall 30-day mortality was 0.9%. The AVR AD<45-mm group had adjusted short- and medium-term survival similar to that of the AVR/AN AD 45- to 49-mm and AVR/AN AD≥50-mm groups, with a 30-day mortality of 0.8%, 0%, and 1.9%, respectively (P=.41). The propensity score-matched AVR/AN AD≥50-mm group had significantly greater rates of reintubation than either the AVR AD<45-mm (P=.012) or AVR/AN AD 45- to 49-mm (P=.04) group and greater rates of prolonged ventilation (P=.022) than the AVR AD<45-mm group. No significant differences were found in reoperation or myocardial infarction among the subgroups. CONCLUSIONS In patients with undergoing AVR, no increase was seen in morbidity or mortality when adding aortic replacement with an AD of 45 to 49 mm, in accordance with the 2006 ACC/AHA guidelines, although the AVR/AN AD≥50-mm group had a greater risk of respiratory complications. Our findings indicate that compliance with the ACC/AHA guidelines is safe in select centers.

Prosthesis-patient mismatch in bovine pericardial aortic valves: Evaluation using 3 different modalities and associated medium-term outcomes

Background— The prevalence of prosthesis-patient mismatch (PPM) and its impact on survival after aortic valve replacement have not been clearly defined. Historically, the presence of PPM was identified from postoperative echocardiograms or preoperative manufacturer-provided charts, resulting in wide discrepancies. The 2009 American Society of Echocardiography (ASE) guidelines proposed an algorithmic approach to calculate PPM. This study compared PPM prevalence and its impact on survival using 3 modalities: (1) the ASE guidelines–suggested algorithm (ASE PPM); (2) the manufacturer-provided charts (M PPM); and (3) the echocardiographically measured, body surface area–indexed, effective orifice area (EOAi PPM) measurement. Methods and Results— A total of 614 patients underwent aortic valve replacement with bovine pericardial valves from 2004 to 2009 and had normal preoperative systolic function. EOAi PPM was severe if EOAi was ≤0.60 cm2/m2, moderate if EOAi was 0.60 to 0.85 cm2/m2, and absent (none) if EOAi was ≥0.85 cm2/m2. ASE PPM was severe in 22 (3.6%), moderate in 6 (1%), and absent (none) in 586 (95.4%). ASE PPM was similar to manufacturer-provided PPM ( P =1.00). ASE PPM differed significantly from EOAi PPM ( P <0.001), which identified severe mismatch in 170 (29.7%), moderate in 191 (33.4%), and absent (none) in 211 patients (36.9%). Irrespective of the PPM classification method, PPM did not adversely affect midterm survival (average follow-up, 4.1±1.8 years; median, 3.9 years; range, 0.01–8 years). There were no reoperations for PPM. Conclusions— In patients with normal systolic function undergoing bovine pericardial aortic valve replacement, the prevalence of PPM using the algorithmic-ASE approach was low and correlated well with manufacturer-provided PPM. Independent of the method of PPM assessment, PPM was not associated with medium-term mortality.Background— The prevalence of prosthesis-patient mismatch (PPM) and its impact on survival after aortic valve replacement have not been clearly defined. Historically, the presence of PPM was identified from postoperative echocardiograms or preoperative manufacturer-provided charts, resulting in wide discrepancies. The 2009 American Society of Echocardiography (ASE) guidelines proposed an algorithmic approach to calculate PPM. This study compared PPM prevalence and its impact on survival using 3 modalities: (1) the ASE guidelines–suggested algorithm (ASE PPM); (2) the manufacturer-provided charts (M PPM); and (3) the echocardiographically measured, body surface area–indexed, effective orifice area (EOAi PPM) measurement. Methods and Results— A total of 614 patients underwent aortic valve replacement with bovine pericardial valves from 2004 to 2009 and had normal preoperative systolic function. EOAi PPM was severe if EOAi was ⩽0.60 cm2/m2, moderate if EOAi was 0.60 to 0.85 cm2/m2, and absent (none) if EOAi was ≥0.85 cm2/m2. ASE PPM was severe in 22 (3.6%), moderate in 6 (1%), and absent (none) in 586 (95.4%). ASE PPM was similar to manufacturer-provided PPM (P=1.00). ASE PPM differed significantly from EOAi PPM (P<0.001), which identified severe mismatch in 170 (29.7%), moderate in 191 (33.4%), and absent (none) in 211 patients (36.9%). Irrespective of the PPM classification method, PPM did not adversely affect midterm survival (average follow-up, 4.1±1.8 years; median, 3.9 years; range, 0.01–8 years). There were no reoperations for PPM. Conclusions— In patients with normal systolic function undergoing bovine pericardial aortic valve replacement, the prevalence of PPM using the algorithmic-ASE approach was low and correlated well with manufacturer-provided PPM. Independent of the method of PPM assessment, PPM was not associated with medium-term mortality.

New understanding about calcific aortic stenosis and opportunities for pharmacologic intervention.

Purpose of review This review article will discuss aortic stenosis, the evolving studies defining the cellular mechanisms and the potential for medical therapies for the treatment of this disease. Recent findings Currently, the only therapy for these patients is surgical valve replacement. In the past decade there has been a change in the paradigm towards our understanding of the cellular biology of this disease process. Studies in laboratories across the world have demonstrated that this disease has an active biology and that this biology may be targeted with medical therapies similar to that of vascular atherosclerosis. Summary Calcific aortic stenosis is the third most common form of cardiovascular disease in the USA. It has replaced rheumatic heart disease in prevalence in western countries due to improved access to healthcare and the widespread use of antibiotics.

Statin Use and Aneurysm Risk in Patients With Bicuspid Aortic Valve Disease

No medical therapy has been proven to prevent the progression of aortic dilatation in bicuspid aortic valve (BAV) disease, and prophylactic aortic surgery remains the mainstay of treatment.

Assessment of altered three-dimensional blood characteristics in aortic disease by velocity distribution analysis.

To test the feasibility of velocity distribution analysis for identifying altered three‐dimensional (3D) flow characteristics in patients with aortic disease based on 4D flow MRI volumetric analysis.