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Mitral annular calcification (MAC) is a progressive degenerative process associated with comorbidities and increased mortality. A staging system that considers extramitral cardiac damage in MAC may help improve patient selection for mitral valve interventions. This study sought to develop a transthoracic echocardiogram (TTE)-based cardiac staging system in patients with MAC and significant mitral valve dysfunction and assess its prognostic utility. We retrospectively evaluated all adults who underwent TTE over 1 year at Mayo Clinic with MAC and significant mitral valve dysfunction defined as mitral stenosis and/or at least moderate mitral regurgitation. Patients were categorized into 5 stages according to extramitral cardiac damage by TTE. All-cause mortality and heart failure hospitalization were assessed. For the 953 included patients, the mean age was 76.2 ± 10.7 years, and 54.0% were women. Twenty-eight (2.9%) patients were classified in stages 0 to 1, 499 (52.4%) in stage 2, 115 (12.1%) in stage 3, and 311 (32.6%) in stage 4. At the 3.8-year follow-up, mortality was significantly higher in patients in stages 2 to 4 compared to stages 0 to 1 and increased with each stage. Survival differences were maintained after adjustment for age, diabetes mellitus, and glomerular filtration rate. The rate of heart failure hospitalization was significantly higher in stages 3 and 4 compared to stages 0 to 1. Similar results were observed in subgroup analysis in patients with moderate or severe MAC, predominant mitral stenosis, or predominant mitral regurgitation. Using the proposed extramitral cardiac damage staging system in patients with MAC and significant mitral valve dysfunction, more advanced stages are associated with higher mortality. [Display omitted] [ABSTRACT FROM AUTHOR]

Aims: Aortic stenosis (AS) induces characteristic changes in left ventricular (LV) mechanics that can be reversed after aortic valve replacement (AVR). We aimed to comprehensively characterize LV mechanics before and after AVR in patients with severe AS and identify predictors of short-term functional recovery and long-term survival. Methods and results: We prospectively performed comprehensive strain analysis by 2D speckle-tracking echocardiography in 88 patients with severe AS and LV ejection fraction ≥50% (mean age 71 ± 12 years, 42% female) prior to and within 7 days after AVR. Patients were followed for up to 5.2 years until death from any cause or last encounter. Within days after AVR, we observed an absolute increase in global longitudinal strain (GLS) (−16.0 ± 2.0% vs. −18.5 ± 2.1%, P<0.0001) and a decrease in apical rotation (10.5 ± 4.0° vs. 8.3 ± 2.8°, P = 0.0002) and peak systolic twist (18.2 ± 5.0° vs. 15.5 ± 3.8°, P = 0.0008). A baseline GLS is less negative than −16.2% was 90% sensitive and 67% specific in predicting a ≥ 20% relative increase in GLS. During a median follow-up of 3.8 years, a global circumferential systolic strain rate (GCSRs) less negative than −1.9% independently predicted lower survival. Conclusion: In patients with severe AS, a reversal in GLS, apical rotation, and peak systolic twist abnormalities towards normal occurs within days of AVR. Baseline GLS is the strongest predictor of GLS recovery but neither was associated with long-term survival. In contrast, abnormal baseline GCSRs are associated with worse outcomes. Graphical Abstract [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate outcomes of transcatheter mitral valve replacement (TMVR) with transfemoral access in patients at prohibitive or high surgical risk. Prohibitive surgical risk may preclude mitral valve replacement surgery in some patients. The investigational Intrepid TMVR system has previously been evaluated using transapical access for delivery of a self-expanding bioprosthetic valve. This prospective, multicenter, nonrandomized early feasibility study evaluated the safety and performance of the Intrepid valve using transfemoral access enabling transseptal delivery in patients with moderate to severe or severe symptomatic mitral regurgitation at high surgical risk. Candidacy was determined by heart teams, with approval by a central screening committee. Echocardiographic data were evaluated by an independent core laboratory. Clinical events were adjudicated by a clinical events committee. Fifteen patients were enrolled at 6 sites from February 2020 to May 2021. The median age was 80 years, and median Society of Thoracic Surgeons Predicted Risk of Mortality was 4.7%; 87% of patients were men, and 53% had undergone prior sternotomy. Fourteen implants were successful. One patient was converted to surgery during the index procedure. Patients stayed a median of 5 days postprocedure. There were 6 access site bleeds (40%) and 11 iatrogenic atrial septal defect closures (73%). At 30 days, there were no deaths, strokes, or reinterventions. All patients undergoing implantation had trace or no valvular or paravalvular mitral regurgitation, and the mean gradient was 4.7 mm Hg (IQR: 3.0-6.7 mm Hg). Thirty-day results from the Intrepid transfemoral TMVR early feasibility study demonstrate excellent valve function and no mortality or stroke. Additional patients and longer follow-up are needed to confirm these findings. ([The Early Feasibility Study of the Intrepid™ TMVR Transseptal System]; NCT02322840) [Display omitted] [ABSTRACT FROM AUTHOR]

Aims Beat-to-beat variability in cycle length is well-known in atrial fibrillation (Afib); whether this also translates to variability in annulus size remains unknown. Defining annulus maximal size in Afib is critical for accurate selection of percutaneous devices given the frequent association with mitral and tricuspid valve diseases. Methods and results Images were obtained from 170 patients undergoing 3D echocardiography [100 (50 sinus rhythm (SR) and 50 Afib) for mitral annulus (MA) and 70 (35 SR and 35 Afib) for tricuspid annulus (TA)]. Images were analysed for differences in annular dynamics with a commercially available software. Number of cardiac cycles analysed was 567 in mitral valve and 346 in tricuspid valve. Median absolute difference in maximal MA area over four to six cycles was 1.8 cm2 (range 0.5–5.2 cm2) in Afib vs. 0.8 cm2 (range 0.1–2.9 cm2) in SR, P  < 0.001. Maximal MA area was observed within 30–70% of the R-R interval in 81% of cardiac cycles in SR and in 73% of cycles in Afib. Median absolute difference in maximal TA area over four to six cycles was 1.4 cm2 (range 0.5–3.6 cm2) in Afib vs. 0.7 cm2 (range 0.3–1.7 cm2) in SR, P  < 0.001. Maximal TA area was observed within 60–100% of the R-R interval in 81% of cardiac cycles in SR, but only in 49% of cycles in Afib. Conclusion MA and TA reach maximal size within a broad time interval centred around end-systole and end-diastole, respectively, with significant beat-to-beat variability. Afib leads to a larger beat-to-beat variability in both timing of occurrence and values of annulus size than in SR. [ABSTRACT FROM AUTHOR]

Aims: Concurrent mitral regurgitation (MR) influences treatment considerations in patients with severe aortic stenosis (sAS). Limited information exists regarding haemodynamic effects of sAS on MR severity and outcome of these patients. We assessed the impact of aortic valve replacement (AVR) on MR according to mechanism in patients with sAS and MR. Methods and results: In patients with sAS who received surgical or transcatheter AVR from 2008 to 2017, those with effective mitral regurgitant orifice area (ERO) ≥ 10 mm2 prior to AVR were evaluated. The change in MR after AVR was considered significant when there was at least one grade difference. We compared the all‐cause mortality of patients with and without improvement in MR. Of 234 patients with sAS and MR (age 80 ± 9 years, 52% male, ERO 19 ± 7 mm2), organic and functional MR were present in 166 (71%) and 68 (29%), respectively. MR improved in 136 (58%); improvement occurred with similar frequency in organic versus functional MR (59% and 57%, P = 0.88). Associated determinants were absence of atrial fibrillation in organic MR [odds ratio (OR) 2.09, 95% confidence interval (CI) 1.00–4.37; P = 0.049] and indexed aortic valve area (iAVA) ≤ 0.40 cm2 in functional MR (OR 3.28, 95% CI 1.13–9.47; P = 0.028). In the overall cohort, mitral annulus diameter < 3 cm (OR 1.74, 95% CI 1.02–2.97; P = 0.041) and QRS duration < 115 ms (OR 1.73, 95% CI 1.00–2.98; P = 0.049) were independently associated with improvement in MR. During median follow‐up of 3.5 years, lack of improvement in MR was not associated with higher mortality in the overall cohort of patients with ERO ≥ 20 mm2 [adjusted hazard ratio (HR) 1.71, 95% CI 0.90–3.27; P = 0.10, adjusted for age, New York Heart Association III or IV, diabetes, and creatinine ≥ 2.0 mg/dL]. Lack of improvement in organic MR was associated with higher mortality (adjusted HR 3.36, 95% CI 1.40–8.05; P < 0.01). In patients with functional MR, change in MR was not associated with mortality (HR 1.24, 95% CI 0.44–3.47; P = 0.68). Conclusions: In nearly 60% of patients with sAS and MR, MR improved after AVR, even in the majority of patients with organic MR. Absence of atrial fibrillation in organic MR, iAVA ≤ 0.40 cm2 in functional MR, and mitral annulus diameter < 3 cm and QRS duration < 115 ms in the overall population were associated with MR improvement. Post‐operative improvement in organic MR was associated with better survival. [ABSTRACT FROM AUTHOR]

BACKGROUND: Atrial fibrillation (AF) is a low-flow state and may underestimate aortic stenosis (AS) severity. Single-high Doppler signals (HS) consistent with severe AS (peak velocity ≥4 m/s or mean gradient ≥40 mmHg) are averaged down in current practice. The objective for the study was to determine the significance of HS in AF low-gradient AS (LGAS). METHODS: One thousand five hundred forty-one patients with aortic valve area ≤1 cm² and left ventricular ejection fraction ≥50% were identified and classified as high-gradient AS (HGAS) (≥40 mmHg) and LGAS (<40 mmHg), and AF versus sinus rhythm (SR). Available computed tomography aortic valve calcium scores (AVCS) were retrieved from the medical record. Outcomes were assessed. RESULTS: Mean age was 76±11 years, female 47%. Mean gradient was 51±12 in SR-HGAS, 48±10 in AF-HGAS, 31±5 in SR-LGAS, and 29±7 mmHg in AF-LGAS, all P≤0.001 versus SR-HGAS; HS were present in 33% of AF-LGAS. AVCS were available in 34%. Compared with SR-HGAS (2409 arbitrary units; interquartile range, 1581–3462) AVCS were higher in AFHGAS (2991 arbitrary units; IQR1978–4229, P=0.001), not different in AF-LGAS (2399 arbitrary units; IQR1817–2810, P=0.47), and lower in SR-LGAS (1593 arbitrary units; IQR945–1832, P<0.001); AVCS in AF-LGAS were higher when HS were present (P=0.048). Compared with SR-HGAS, the age-, sex-, comorbidity index-, and time-dependent aortic valve replacement-adjusted mortality risk was higher in AF-HGAS (hazard ratio=1.82 [1.40–2.36], P<0.001) and AF-LGAS with HS (hazard ratio=1.54 [1.04–2.26], P=0.03) but not different in AF-LGAS without HS or SR-LGAS (both P=not significant). CONCLUSIONS: Severe AS was common in AF-LGAS. AVCS in AF-LGAS were not different from SR-HGAS. AVCS were higher and mortality worse in AF-LGAS when HS were present. [ABSTRACT FROM AUTHOR]

Background: Ventricular strain measurements vary depending on cardiac chamber (left ventricle [LV] or right ventricle [RV]), type of strain (longitudinal, circumferential, or radial), ventricular level (basal, mid, or apical), myocardial layer (endocardial or epicardial), and software used for analysis, among other demographic factors such as age and gender. Here, we present an analysis of ventricular strain taking all of these variables into account in a cohort of patients with no structural heart disease using a vendor-independent speckle-tracking software.Methods: LV and RV full-thickness strain parameters were retrospectively measured in 102 patients (mean age 39 ± 15 years; 62% female). Within this cohort, we performed further layer-specific strain analysis in 20 subjects. Data were analyzed for global and segmental systolic strain, systolic strain rate, early diastolic strain rate, and their respective time-to-peak values.Results: Mean LV global longitudinal, circumferential, and radial strain values for the entire cohort were - 18.4 ± 2.0%, - 22.1 ± 4.1%, and 43.9 ± 12.1% respectively, while mean RV global and free wall longitudinal strain values were - 24.2 ± 3.9% and - 26.1 ± 5.2% respectively. Women on average demonstrated higher longitudinal and circumferential strain and strain rate than men, and longer corresponding time-to-peak values. Longitudinal strain measurements were highest at the apex compared with the mid ventricle and base, and in the endocardium compared with the epicardium. Longitudinal strain was the most reproducible measure, followed closely by circumferential strain, while radial strain showed suboptimal reproducibility.Conclusions: We present an analysis of ventricular strain in patients with no structural heart disease using a vendor-independent speckle-tracking software. [ABSTRACT FROM AUTHOR]

Objectives: To examine the prognostic significance of atrial fibrillation (AF) versus sinus rhythm (SR) on the management and outcomes of patients with severe aortic stenosis (AS).Methods: 1847 consecutive patients with severe AS (aortic valve area ≤1.0 cm2 and aortic valve systolic mean Doppler gradient ≥40 mm Hg or peak velocity ≥4 m/s) and left ventricular ejection fraction ≥50% were identified. The independent association of AF and all-cause mortality was assessed.Results: Age was 76±11 years and 46% were female; 293 (16%) patients had AF and 1554 (84%) had SR. In AF, 72% were symptomatic versus 71% in SR. Survival rate at 5 years for AF (41%) was lower than SR (65%) (age- and sex-adjusted HR=1.66 (1.40-1.98), p<0.0001). In multivariable analysis, factors associated with mortality included age (HR per 10 years=1.55 (1.42-1.69), p<0.0001), dyspnoea (HR=1.58 (1.33-1.87), p<0.0001), ≥ moderate mitral regurgitation (HR=1.63 (1.22-2.18), p=0.001), right ventricular systolic dysfunction (HR=1.88 (1.52-2.33), p<0.0001), left atrial volume index (HR per 10 mL/m2=1.13 (1.07-1.19), p<0.0001) and aortic valve replacement (AVR) (HR=0.44 (0.38-0.52), p<0.0001). AF was not a predictor of mortality independent of variables strongly correlated HR=1.02 (0.84-1.25), p=0.81). The 1-year probability of AVR following diagnosis of severe AS was lower in AF (49.8%) than SR (62.5%) (HR=0.73 (0.62-0.86), p<0.001); among patients with AF not referred for AVR, symptoms were frequently attributed to AF instead of AS.Conclusion: AF was associated with poor prognosis in patients with severe AS, but apparent differences in outcomes compared with SR were explained by factors other than AF including concomitant cardiac abnormalities and deferral of AVR due to attribution of cardiac symptoms to AF. [ABSTRACT FROM AUTHOR]

We describe a case of a mass‐like echocardiographic density on a mechanical prosthetic aortic valve. We initially suspected a thrombus vs vegetation on transthoracic echocardiography, but after transesophageal echocardiography, the density was subsequently determined to be cavitation by reviewing the initial images in slow motion. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Abstract: 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. [Copyright &y& Elsevier]

Background: Investigational transcatheter edge-to-edge repair (TEER) for severe tricuspid regurgitation (TR) has shown promise as an alternative to surgery, but factors influencing outcomes, optimal patient selection, and procedural timing remain incompletely defined. Given the limitations of determining TR severity by conventional echocardiography, our objectives were to determine whether invasive right atrial (RA) pressures performed during the procedure are related to patient outcomes. Methods: This study was a retrospective review of patients who underwent off-label tricuspid TEER using MitraClip (Abbott Vascular, Menlo Park, CA) for significant TR at a single institution. Intraprocedural mean RA pressure, RA peak V-wave, RA pressure nadir, and systolic increase in RA pressure (XV height) were recorded. Results: Thirty-eight patients underwent tricuspid TEER; 33 underwent concomitant mitral TEER for mitral regurgitation. The study cohort was 39% female with a mean age of 78.6+/-14.3 years. Median follow-up was 339 days (interquartile range, 100-601). Any reduction in mean RA pressure, RA peak V-wave, RA nadir, and XV height occurred in 74%, 82%, 45%, and 87% of patients, respectively. At 1 year, event-free survival was 47%. Postprocedure XV height correlated with TR severity as determined by echocardiography (P <0.0001).>8 mm Hg) had worse event-free survival compared with those who had concluding XV height <=8 mm Hg (P =0.02). Attainment of a concluding XV height less than or equal to median value was associated with a lower creatinine the next day (1.27+/-0.47 versus 1.64+/-0.47 mg/dL, P =0.04). /p> Conclusions: Intraprocedural XV height correlates with TR severity after tricuspid TEER, and lower concluding pressures are associated with improved outcomes. Analysis of RA pressures may serve as a complementary tool for the evaluation of disease severity and procedural guidance. * Significant tricuspid regurgitation is associated with morbidity and mortality in isolation and in the presence of other cardiac pathology. * In patients who undergo intervention for severe tricuspid regurgitation, residual regurgitation predicts clinical outcome. However, accurate tricuspid regurgitation quantification can be challenging. * Reductions in invasive measurements of right atrial pressure correlate with procedural success and clinical improvements. * Right atrial pressure nadir and XV height (the difference between the peak V-wave and the X-wave nadir) are novel invasive measurements that correlate with clinical outcomes. [ABSTRACT FROM AUTHOR]

Objective: To determine whether echocardiography-derived left ventricular filling pressure influences survival in patients with severe aortic stenosis (AS) undergoing aortic valve replacement (AVR).Methods: We retrospectively reviewed 1383 consecutive patients with severe AS, normal ejection fraction and interpretable filling pressure undergoing AVR. Left ventricular filling pressure was determined according to current guidelines using mitral inflow, mitral annular tissue Doppler, estimated right ventricular systolic pressure and left atrial volume index. Cox proportional hazards regression was used to assess the influence of various parameters on mortality.Results: Age was 75±10 years and 552 (40%) were female. Left ventricular filling pressure was normal in 325 (23%), indeterminate in 463 (33%) and increased in 595 (43%). Mean follow-up was 7.3±3.7 years, and mortality was 1.2%, 4.2% and 18.9% at 30 days and 1 and 5 years, respectively. Compared with patients with normal filling pressure, patients with increased filling pressure were older (78±9 vs 70±12, p<0.001), more often female (45% vs 35%, p=0.002) and were more likely to have New York Heart Association class III-IV symptoms (35% vs 24%, p=0.004), coronary artery disease (55% vs 42%, p<0.001) and concentric left ventricular hypertrophy (63% vs 37%, p<0.001). After correction for other factors, increased left ventricular filling pressure remained an independent predictor of mortality after successful AVR (adjusted HR 1.45 (95% CI 1.16 to 1.81), p=0.005).Conclusions: Preoperative increased left ventricular filling pressure is common in patients with AS undergoing AVR and has important prognostic implications, regardless of symptom status. Future prospective studies should consider whether patients with increased filling pressure would benefit from earlier operation. [ABSTRACT FROM AUTHOR]

Background: Diet-induced obesity using ad libitum high-fat feeding in rabbits causes losses in diurnal rhythms of blood pressure (BP) and heart rate (HR). Because obesity is associated with hypertension, it is difficult to determine independent effects of ad libitum feeding and obesity in altering diurnal rhythms. We studied diurnal rhythms of BP and HR after controlling BP during obesity development using hydralazine. Methods: New Zealand white rabbits were divided into lean control (LC), lean hydralazine-treated (LH), obese control (OC), and obese hydralazine-treated (OH) groups. Lean animals consumed a maintenance diet, whereas obese animals consumed an ad libitum high-fat diet. Over 12 weeks, BP and HR were monitored from 11:00 to 07:00 using telemetry. Hydralazine treatment consisted of 6 mg/kg/day and 10 to 14 mg/kg/day for LH and OH, respectively. Diurnal rhythms were evaluated using day–night values (day, 11:00 to 16:00 average; night, 02:00 to 07:00 average). Results: Compared with control values, diurnal HR rhythm was abolished on day 1 of high-fat feeding (61.4 ± 3.6 v 3.1 ± 4.2 beats/min, respectively; P ≤ .05), whereas OC and OH did not differ significantly in day–night HR over 12 weeks. Compared with control values, diurnal BP rhythm was abolished by day 2 of high-fat feeding (4.6 ± 1.6 v −0.1 ± 0.9 mm Hg, respectively; P ≤ .05), whereas OC and OH did not differ in day–night BP despite lower BP in OH. Conclusion: In this study ad libitum high-fat feeding in rabbits caused immediate losses of diurnal rhythms of BP and HR that were independent of weight gain and BP elevation. [Copyright &y& Elsevier]