Jeremy J. Thaden

The Global Burden of Aortic Stenosis

Degenerative, calcific valvular aortic stenosis (AS), caused by an active process of atherosclerosis, calcification and ossification, is the most common cause of AS in industrialized nations. The prevalence of calcific AS is age-dependent, and thus is expected to increase due to demographic aging of the global population. It is well recognized that severe AS carries a poor prognosis if left untreated. Despite this recognition, many patients are inappropriately denied surgery because of perceived risk. This article will examine the etiology, prevalence, and current trends in the treatment of degenerative AS focusing on indications for surgical aortic valve replacement.

Sex-related differences in calcific aortic stenosis: correlating clinical and echocardiographic characteristics and computed tomography aortic valve calcium score to excised aortic valve weight

AIMS Calcific aortic valve stenosis (AS) is purportedly associated with less calcium burden in women than in men. We sought to examine sex-related differences and correlates of surgically excised aortic valve weight (AVW) in pure AS. METHODS AND RESULTS Clinical and echocardiographic characteristics of 888 consecutive patients who underwent aortic valve replacement for severe AS were correlated to AVW, and in 126 patients, AVW was also correlated to computed tomography aortic valve calcium (AVC) score. Women and men had similar indexed valve area (0.42 ± 0.09 vs. 0.42 ± 0.07 cm (2)/m(2), P = 0.95) and mean systolic gradient (53 ± 15 vs. 52 ± 13 mmHg, P = 0.11), but women had higher New York Heart Association class (2.63 ± 0.70 vs. 2.50 ± 0.70, P = 0.01) and less prevalent coronary artery disease (38 vs. 52%, P < 0.0001). Aortic valve weight was lower in women (1.94 ± 0.88 vs. 3.08 ± 1.32 g, P < 0.0001) even when indexed to body surface area (1.09 ± 0.48 vs. 1.48 ± 0.62 g/m(2), P < 0.0001) or left ventricular outflow tract (LVOT) area (0.54 ± 0.23 vs. 0.71 ± 0.29 g/cm(2), P < 0.0001). Using multivariate analysis, male sex (P < 0.0001), bicuspid valve (P < 0.0001), and larger LVOT area (P < 0.0001) were the major determinants of increased AVW, along with current cigarette smoking (P = 0.007). Diabetes (P = 0.004) and hypertension (P = 0.03) were independently associated with lower AVW. Aortic valve calcium correlated well with AVW (r = 0.81, P < 0.0001) and was lower in women than in men (2520 ± 1199 vs. 3606 ± 1632 arbitrary units, P < 0.0001). CONCLUSIONS Despite the same degree of AS severity, women have less AVC and lower AVW compared with men, irrespective of valve morphology. Aortic valve calcium is correlated to excised AVW. Hypertension, diabetes, and current cigarette smoking were independently associated with AVW.

Intrinsic Wave Propagation of Myocardial Stretch, A New Tool to Evaluate Myocardial Stiffness: A Pilot Study in Patients with Aortic Stenosis and Mitral Regurgitation

Background Left ventricular (LV) filling following atrial contraction generates LV myocardial stretch that propagates from base to apex with a speed proportional to myocardial elasticity. The aim of this study was to test the hypothesis that intrinsic velocity propagation of myocardial stretch (iVP) would be altered in patients with valvular disease and chronic LV pressure overload or volume overload, which may adversely affect mechanical properties of the LV tissue. A second aim was to compare iVP with flow propagation velocity in the chamber. Methods Sixty subjects were prospectively recruited: 20 with severe aortic stenosis (AS), 20 with severe degenerative mitral regurgitation (MR), and 20 normal control subjects. LV iVP was measured using ultrahigh–frame rate tissue Doppler (350–460 frames/sec) and flow propagation velocity by color flow M‐mode imaging. Follow‐up data (up to 2 years) were retrieved from medical records. Results iVP was highest in patients with AS (2.2 ± 0.7 m/sec), intermediate in those with MR (1.6 ± 0.5 m/sec), and lowest in control subjects (1.4 ± 0.2 m/sec; P < .0001). Fourteen patients with AS and eight with MR had iVP > 1.8 m/sec. Overall, iVP correlated with age, LV morphology, severity of aortic valve obstruction, and measures of LV preload and afterload. At follow‐up, patients with high iVP had lower survival free of major adverse cardiac events (P = .002). Flow propagation velocity was similar between groups and correlated poorly with iVP (r = 0.26, P = .10). Conclusions A significant number of patients with severe AS and severe MR had rapid transmission of myocardial stretch, indicating increased myocardial stiffness. This information was not conveyed by measurement of flow propagation. Larger studies are needed to investigate the clinical utility of this novel measurement. HighlightsNoninvasive quantification of myocardial stiffness remains elusive.A novel approach to estimate myocardial elasticity is proposed.The mechanism relies on intrinsic cardiac waves and theory of wave propagation in elastic tubes.Some patients with valvular heart disease were found to have high diastolic myocardial stiffness.Intraventricular flow propagation was not able to convey this information.

Mitral valve anatomic predictors of hemodynamic success with transcatheter mitral valve repair

Background Mitral regurgitation is a heterogeneous disease. Determining which patients derive optimal outcomes from transcatheter edge‐to‐edge mitral valve repair (TMVR) remains challenging. We sought to determine whether baseline mitral valve anatomic characteristics are predictive of left atrial pressure (LAP) changes during TMVR with MitraClip. Methods and Results Consecutive patients with severe mitral regurgitation undergoing TMVR (n=112) underwent continuous intraprocedural LAP monitoring and retrospective echocardiographic analysis for specific mitral anatomic characteristics. Procedural success (optimal LAP reduction) was defined as ≥40% reduction in left atrial V‐wave pressure compared with baseline. Echocardiographic predictors of optimal LAP reduction and increased postprocedure mean diastolic gradient were evaluated. Mean age was 79±14 years, and 36 patients (32%) were women. Primary, mixed, and secondary mitral regurgitation were present in 78 patients (70%), 22 patients (20%), and 12 patients (10%), respectively. Baseline mean LAP and V‐wave were 22±6 and 38±13 mm Hg; after TMVR, these decreased to 19±5 and 27±10 mm Hg, respectively (P<0.0001 for both). Independent predictors of optimal LAP reduction were the presence of a flail scallop, mitral regurgitation localized to a single scallop, and high‐quality 3‐dimensional echocardiographic imaging. Independent predictors of elevated postprocedure mean diastolic gradient were elevated preprocedure mean diastolic gradient, mitral annular calcification, and implantation of multiple clips. Conclusions Mitral valve pathoanatomic features, including a flail leaflet and single jet, are predictive of optimal LAP reduction with TMVR. High‐quality 3‐dimensional imaging may help select patients with the highest likelihood of optimal hemodynamic results with TMVR. These data expand current knowledge about patient selection for TMVR and deserve further study in larger cohorts.

Recellularization of a novel off-the-shelf valve following xenogenic implantation into the right ventricular outflow tract

Current research on valvular heart repair has focused on tissue-engineered heart valves (TEHV) because of its potential to grow similarly to native heart valves. Decellularized xenografts are a promising solution; however, host recellularization remains challenging. In this study, decellularized porcine aortic valves were implanted into the right ventricular outflow tract (RVOT) of sheep to investigate recellularization potential. Porcine aortic valves, decellularized with sodium dodecyl sulfate (SDS), were sterilized by supercritical carbon dioxide (scCO2) and implanted into the RVOT of five juvenile polypay sheep for 5 months (n = 5). During implantation, functionality of the valves was assessed by serial echocardiography, blood tests, and right heart pulmonary artery catheterization measurements. The explanted valves were characterized through gross examination, mechanical characterization, and immunohistochemical analysis including cell viability, phenotype, proliferation, and extracellular matrix generation. Gross examination of the valve cusps demonstrated the absence of thrombosis. Bacterial and fungal stains were negative for pathogenic microbes. Immunohistochemical analysis showed the presence of myofibroblast-like cell infiltration with formation of new collagen fibrils and the existence of an endothelial layer at the surface of the explant. Analysis of cell phenotype and morphology showed no lymphoplasmacytic infiltration. Tensile mechanical testing of valve cusps revealed an increase in stiffness while strength was maintained during implantation. The increased tensile stiffness confirms the recellularization of the cusps by collagen synthesizing cells. The current study demonstrated the feasibility of the trans-species implantation of a non-fixed decellularized porcine aortic valve into the RVOT of sheep. The implantation resulted in recellularization of the valve with sufficient hemodynamic function for the 5-month study. Thus, the study supports a potential role for use of a TEHV for the treatment of valve disease in humans.

Midterm Sapien Transcatheter Valve Durability: Ready for Prime Time or Waiting to Fail?

S ince the first in human transcatheter aortic valve replacement (TAVR) was performed nearly 15 years ago (1), it has been estimated that more than 250,000 procedures have been performed worldwide. The procedure has been refined, and there has been tremendous growth in the evidence supporting its application for intermediate and high-risk patients with symptomatic severe aortic stenosis. The study by Daubert et al. (2), in this issue of iJACC adds to the burgeoning evidence that TAVR is an attractive alternative to surgical valve replacement (SAVR) in high-risk patients. In this study, investigators sought to evaluate longterm durability of the Sapien balloon-expandable TAVR bioprosthesis by using PARTNER I (Placement of Aortic Transcatheter Valves) trial echocardiographic data (3,4). Investigators compared echocardiographic parameters of prosthetic valve function at the time of the first post-implantation echocardiogram to the same parameters 5 years later. In 86 TAVR patients alive at 5 years, without repeat AVR and having followup echocardiography at that time, parameters of prosthetic valve function were stable, and echocardiographic evidence of valve degeneration or worsening paraprosthetic regurgitation was uncommon. Five (5.8%) of the 86 TAVR subjects had an increase in mean systolic gradient

Eosinophilic endocarditis and Strongyloides stercoralis.

10 mm Hg. None of the 86 patients developed new severe regurgitation during follow-up. Transvalvular and paravalvular aortic regurgitation, aortic valve area, mean gradient, stroke

Cardiac Myxoma: The Great Mimicker

A 40-year-old woman from El Salvador presented with 3 months of abdominal pain and diarrhea followed by 2 weeks of atypical chest pain and exertional dyspnea and was diagnosed with eosinophilic endocarditis secondary to Strongyloides stercoralis infection. Transthoracic echocardiogram revealed apical masses in the left and right ventricles and a thickened posterior mitral valve leaflet and cardiac magnetic resonance imaging confirmed the presence of a left ventricular apical mass with diffuse subendocardial delayed enhancement consistent with endocardial fibrosis. In conclusion, eosinophilic endocarditis is a rare cause of restrictive cardiomyopathy characterized by endomyocardial fibrosis and apical thrombosis and fibrosis with frequent involvement of the posterior mitral valve leaflet.

Association Between Echocardiography Laboratory Accreditation and the Quality of Imaging and Reporting for Valvular Heart DiseaseCLINICAL PERSPECTIVE

Cardiac myxoma is the most common primary cardiac neoplasm in adults. They most commonly arise within the left atrium, but may arise from other cardiac chambers, rarely from the valves. Histologically, cardiac myxomas consist of lepidic (“myxoma”) cells within a myxoid stroma. They can be of

Incidence and Management of Hemopericardium: Impact of Changing Trends in Invasive Cardiology

Background— It is presumed that echocardiographic laboratory accreditation leads to improved quality, but there are few data. We sought to compare the quality of echocardiographic examinations performed at accredited versus nonaccredited laboratories for the evaluation of valvular heart disease. Methods and Results— We enrolled 335 consecutive valvular heart disease subjects who underwent echocardiography at our institution and an external accredited or nonaccredited institution within 6 months. Completeness and quality of echocardiographic reports and images were assessed by investigators blinded to the external laboratory accreditation status and echocardiographic results. Compared with nonaccredited laboratories, accredited sites more frequently reported patient sex (94% versus 78%; P<0.001), height and weight (96% versus 63%; P<0.001), blood pressure (86% versus 39%; P<0.001), left ventricular size (96% versus 83%; P<0.001), right ventricular size (94% versus 80%; P=0.001), and right ventricular function (87% versus 73%; P=0.006). Accredited laboratories had higher rates of complete and diagnostic color (58% versus 35%; P=0.002) and spectral Doppler imaging (45% versus 21%; P<0.0001). Concordance between external and internal grading of external studies was improved when diagnostic quantification was performed (85% versus 69%; P=0.003), and in patients with mitral regurgitation, reproducibility was improved with higher quality color Doppler imaging. Conclusions— Accredited echocardiographic laboratories had more complete reporting and better image quality, while echocardiographic quantification and color Doppler image quality were associated with improved concordance in grading valvular heart disease. Future quality improvement initiatives should highlight the importance of high-quality color Doppler imaging and echocardiographic quantification to improve the accuracy, reproducibility, and quality of echocardiographic studies for valvular heart disease.