Does valve size impact hemodynamic, left ventricular mass regression, and prosthetic valve deterioration with a sutureless aortic valve?

OBJECTIVE: To assess the mid-term clinical outcomes, hemodynamics, left ventricular (LV) mass regression, and structural valve deterioration (SVD) in patients implanted with the Perceval aortic sutureless valve across valve sizes. METHODS: Data were obtained from a multicenter European trial and a US Investigational Device Exemption trial. Echocardiography data were analyzed by an echocardiography core lab. A mixed-effects regression model was used to assess relationships between hemodynamic outcomes, time from the procedure, and valve sizes. The Valve Academic Research Consortium (VARC)-3 definition for bioprosthetic valve failure was applied. RESULTS: A Perceval sutureless valve was implanted in 970 patients. The median patient age was 77.8 years, 57.2% were female, the median Society of Thoracic Surgeons predicated risk of mortality was 3.3% (range, 2.1%-6.2%), and 33.4% had a concomitant procedure. The median clinical follow-up was 45.7 months (range, 28.2-76.1 months). Small and medium valves were implanted more commonly in women than in men (16.9% vs 1.9% for small and 55.1% vs 19.5% for medium; P < .001). The mean aortic valve gradients decreased significantly postimplantation and remained stable across all valve sizes throughout the follow-up period. All patients were free from severe patient-prosthesis mismatch (with an effective orifice area/m2 of >0.8). Significant LV mass regression was documented regardless valve sizes, plateaued at -9.1% at 5 years. Freedom from SVD and reintervention were 95.2% and 96.3%, respectively, at 5 years and were independent of implanted valve size (P = .22). The VARC-3 stage 3 bioprosthetic valve failure rate was low, 2.8% at 5 years. CONCLUSIONS: The Perceval valve demonstrated low and stable mean gradients, significant LV mass regression, and low SVD and reintervention rates across all valve sizes.

Excess Reintervention With Mitroflow Prosthesis for Aortic Valve Replacement: Ten-Year Outcomes of a Randomized Trial.

BACKGROUND: Current bioprostheses are considered to have improved durability and better hemodynamic performance compared with previous designs, but there are limited comparative data on late outcomes. METHODS: From 2009 through 2011, 300 adults with severe aortic valve stenosis undergoing aortic valve replacement (AVR) were randomly assigned to receive Edwards Magna, St Jude Epic, or Sorin Mitroflow bioprostheses (n = 100, n = 101, n = 99, respectively). Overall survival was analyzed using Kaplan-Meier and Cox proportional hazards methods, whereas competing risk analysis was used for all time-to-event outcomes. Serial echocardiographic data were fitted with longitudinal models stratified by implant valve size. RESULTS: During median follow-up of 9.8 years (interquartile range, 8.7-10.2), 10-year survival was 50% for the Magna group, 42% for the Epic group, and 41% for the Mitroflow group (P = .415). Cumulative risk of stroke was 9% at 10 years, and rates were comparable for the three groups. Indexed aortic valve area and mean gradients were similar among the three groups receiving 19 mm and 21 mm valves, but in larger (23 mm or more) prostheses, gradients were lower (P < .001) and indexed aortic valve areas were higher in the Magna group (P < .001). The 10-year risk of endocarditis differed by group (P = .033), with higher incidence in the Mitroflow vs the Magna group (7% vs 0%, P = .019). Late risk of reinterventions in the Mitroflow group was 22%, compared with 0% in the Magna group (P < .001) and 5% in the Epic group (P = .008). CONCLUSIONS: The Magna valve had the lowest gradients and largest indexed aortic valve area with larger implant sizes. The Mitroflow bioprosthesis is associated with an increased rate of reintervention and possible increased risk of infection compared with Magna and Epic valves.

5-Year Follow-Up From the PARTNER 2 Aortic Valve-in-Valve Registry for Degenerated Aortic Surgical Bioprostheses.

OBJECTIVES: The aim of this study was to report the outcomes of valve-in-valve (ViV) transcatheter aortic valve replacement (TAVR) at 5 years. BACKGROUND: TAVR for degenerated surgical bioprostheses in patients at high risk for reoperative surgery is an important treatment option that may delay or obviate the need for surgical intervention; however, long-term outcomes of this procedure are unknown. METHODS: The PARTNER (Placement of Aortic Transcatheter Valves) 2 ViV and continued access registries prospectively enrolled patients with failed surgical bioprostheses at high risk for reoperation. Five-year clinical and echocardiographic follow-up data were obtained in 95.9% of patients. RESULTS: In 365 (96 registry and 269 continued access) patients, the mean age was 78.9 ± 10.2 years, the mean Society of Thoracic Surgeons predicted risk of surgical mortality score was 9.1 ± 4.7%, and New York Heart Association functional class was III or IV in 90.4%. At 5 years, the Kaplan-Meier rates of all-cause mortality and any stroke were 50.6% and 10.5%, respectively. Using Valve Academic Research Consortium 3 definitions, the incidence of structural valve deterioration, related hemodynamic valve deterioration, or bioprosthetic valve failure at 5 years was 6.6%. Aortic valve re-replacement was performed in 6.3% (n = 14), the majority of which was due to stenosis (n = 6) and combined aortic insufficiency/paravalvular regurgitation (n = 3). The mean gradient, Doppler velocity index, paravalvular regurgitation, and quality of life measured by Kansas City Cardiomyopathy Questionnaire scores in survivors remained stable from 30 days postprocedure through 5 years. CONCLUSIONS: At the 5-year follow-up, TAVR for bioprosthetic aortic valve failure in high surgical risk patients was associated with sustained improvement in clinical and echocardiographic outcomes.

The role of renin-angiotensin system activated phagocytes in the SARS-CoV-2 coronavirus infection.

OBJECTIVE: Management of the pandemic caused by the novel coronavirus SARS-CoV-2 challenges both scientists and physicians to rapidly develop, and urgently assess, effective diagnostic tests and therapeutic interventions. The initial presentation of the disease in symptomatic patients is invariably respiratory, with dry cough being the main symptom, but an increasing number of reports reveal multiple-organ involvement. The aim of this review is to summarize the potential role of the renin-angiotensin system activated phagocytes in the pathogenesis of COVID-19 disease. METHODS: Data for this review were identified by searches of PubMed and references from relevant articles using the search terms "SARS," "COVID-19," "renin-angiotensin-system," "phagocyte," "reactive free radical," "antioxidant," "ARDS," "thrombosis," "myocardial," "ischaemia," "reperfusion," "microvascular," and "ACE2." Abstracts and reports from meetings were not included in this work. Only articles published in English between 1976 and 2020 were reviewed. RESULTS: The cellular target of SARS viruses is the angiotensin-converting enzyme 2, a critical regulating protein in the renin-angiotensin system. The elimination of this enzyme by the viral spike protein results in excessive activation of phagocytes, migration into the tissues via the high endothelial venules, and an oxidative burst. In the case of an overstimulated host immune response, not only devastating respiratory symptoms but even systemic or multiorgan involvement may be observed. CONCLUSIONS: Early-stage medical interventions may assist in returning the exaggerated immune response to a normal range; however, some therapeutic delay might result in excessive tissue damages, occasionally mimicking a systemic disease with a detrimental outcome.

The senescence-associated secretome as an indicator of age and medical risk.

Produced by senescent cells, the senescence-associated secretory phenotype (SASP) is a potential driver of age-related dysfunction. We tested whether circulating concentrations of SASP proteins reflect age and medical risk in humans. We first screened senescent endothelial cells, fibroblasts, preadipocytes, epithelial cells, and myoblasts to identify candidates for human profiling. We then tested associations between circulating SASP proteins and clinical data from individuals throughout the life span and older adults undergoing surgery for prevalent but distinct age-related diseases. A community-based sample of people aged 20-90 years (retrospective cross-sectional) was studied to test associations between circulating SASP factors and chronological age. A subset of this cohort aged 60-90 years and separate cohorts of older adults undergoing surgery for severe aortic stenosis (prospective longitudinal) or ovarian cancer (prospective case-control) were studied to assess relationships between circulating concentrations of SASP proteins and biological age (determined by the accumulation of age-related health deficits) and/or postsurgical outcomes. We showed that SASP proteins were positively associated with age, frailty, and adverse postsurgery outcomes. A panel of 7 SASP factors composed of growth differentiation factor 15 (GDF15), TNF receptor superfamily member 6 (FAS), osteopontin (OPN), TNF receptor 1 (TNFR1), ACTIVIN A, chemokine (C-C motif) ligand 3 (CCL3), and IL-15 predicted adverse events markedly better than a single SASP protein or age. Our findings suggest that the circulating SASP may serve as a clinically useful candidate biomarker of age-related health and a powerful tool for interventional human studies.

Use of left atrial appendage occlusion among older cardiac surgery patients with preoperative atrial fibrillation: a national cohort study.

PURPOSE: Patients with atrial fibrillation (AF) undergoing cardiac surgery are at substantially increased risk for stroke. Increasing evidence has suggested that surgical left atrial appendage occlusion (S-LAAO) may have the potential to substantially mitigate this stroke risk; however, S-LAAO is performed in a minority of patients with AF undergoing cardiac surgery. We sought to identify factors associated with usage of S-LAAO. METHODS: In a nationally-representative, contemporary cohort (07/2011-06/2012) of older patients undergoing cardiac surgery with preoperative AF (n = 11,404) from the Medicare-linked Society of Thoracic Surgeons Adult Cardiac Surgery Database, we evaluated patient and hospital characteristics associated with S-LAAO use by employing logistic and linear regression models. RESULTS: In this cohort (average age, 76 years; 39% female), 4177 (37%) underwent S-LAAO. Neither S-LAAO nor discharge anticoagulation was used in 25% ("unprotected" patients). The overall propensity for S-LAAO decreased significantly with increasing CHA2DS2-VASc (congestive heart failure; hypertension; age 75 years or older; diabetes mellitus; stroke, transient ischemic attack, or thromboembolism; vascular disease; age 65 to 74 years; sex category (female)) score (ptrend < 0.001). There was substantial variability in S-LAAO use across geographic regions, and S-LAAO was more commonly performed at academic and higher-volume valve surgery centers. CONCLUSIONS: Substantial variability in use of S-LAAO exists. In many instances, the procedure is being deferred in the patients that may be poised to benefit the most (i.e., those with increased CHA2DS2-VASc score-defined stroke risk).

Changes in Right Ventricle Function After Mitral Valve Repair Surgery.

BACKGROUND: Right ventricular (RV) dysfunction can occur after cardiac surgery and persist for years. We assessed perioperative RV systolic function in patients undergoing mitral valve (MV) repair and further compared minimally invasive robotic-assisted mitral valve repair (MIMVr) vs standard 'open' MV repair (MVr). Speckle tracking (RV free wall strain [RVS]) was used as a sensitive echocardiography method to assess RV function. METHODS: Retrospective analysis, over 3 years, of consecutive patients (n = 158) referred to Mayo Clinic (Rochester, MN, USA). Preoperative, pre-discharge and 1 year transthoracic echocardiograms were reviewed. A prospective pilot study was performed for sample size estimation. Primary outcome was RV free wall strain (RVS). RESULTS: Right ventricular free wall strain declined after MV repair surgery (-22.6 ± 7% vs -15 ± 6%, p < 0.001). There were smaller reductions in RVS in MIMVr vs MVr group (-6.0 ± 9% vs -10.3 ± 8%, p < 0.01), which persisted after adjusting for baseline values (RVS treatment effect 1.5%, p = 0.007). There was greater recovery in MIMVr vs MVr group at 1 year follow-up vs pre-surgery values (-3.4 ± 9% vs -8.1 ± 8% respectively, p < 0.001, RVS treatment effect 1.7%, p = 0.001). Bypass time was higher in the MIMVr group (80min ± 22 vs 40min ± 20, p < 0.0001). The echo findings remained significant correcting for age, pulmonary pressures and change in ejection fraction. CONCLUSIONS: Right ventricular systolic dysfunction is common after MV repair surgery. Deterioration in RV contraction is less pronounced following MIMVr vs MVr and is associated with enhanced RV functional recovery at 1 year, albeit not to preoperative levels. This may potentially be associated with clinical functional improvement but further studies are warranted to investigate this.

Low-Risk Transcatheter Versus Surgical Aortic Valve Replacement - An Updated Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: To perform a meta-analysis including all available randomized controlled trials (RCTs) to date comparing transcatheter aortic valve replacement (TAVR) to surgical aortic valve replacement (SAVR) in patients with severe aortic stenosis (AS) and low surgical risk. BACKGROUND: Current guidelines recommend SAVR for patients with severe symptomatic AS and low surgical risk. A few RCTs have evaluated TAVR in low surgical risk patients but equipoise exists related to TAVR valve durability, paravalvular leak (PVL) and role of TAVR in younger, low surgical risk patients. METHODS: Five databases were analyzed from January-2000 to March-2019 for RCTs comparing SAVR to TAVR in low-risk severe AS patients. RESULTS: Four RCTs on low-risk TAVR patients with 2887 patients were included. Mean follow-up was ~24.1 ±â€¯24 months. Early mortality was lower with TAVR compared to SAVR (RR: 0.44, 95% CI: 0.20-0.95, P = 0.038) whereas long-term mortality was similar (RR: 0.67, 95% CI: 0.39-1.14, P = 0.141). Both early and long-term stroke rates were similar. TAVR was associated with lower risk of atrial fibrillation, major bleeding, acute kidney injury (AKI) and rehospitalization, but higher rates of permanent pacemaker implantation (PPM) and moderate or severe PVL. There was no difference in major vascular complications, myocardial infarction, endocarditis, aortic valve gradients and valve area at follow-up. CONCLUSIONS: In low-risk patients with severe AS, TAVR has a lower early mortality compared to SAVR with no difference in long-term mortality. Although complication rates varied between TAVR and SAVR, our study findings suggest that transfemoral-TAVR is an appropriate treatment option for severe symptomatic AS in patients with low surgical risk.

3-Year Outcomes After Valve-in-Valve Transcatheter Aortic Valve Replacement for Degenerated Bioprostheses: The PARTNER 2 Registry.

BACKGROUND: Transcatheter aortic valve replacement (TAVR) for degenerated surgical bioprosthetic aortic valves is associated with favorable early outcomes. However, little is known about the durability and longer-term outcomes associated with this therapy. OBJECTIVES: The aim of this study was to examine late outcomes after valve-in-valve TAVR. METHODS: Patients with symptomatic degeneration of surgical aortic bioprostheses at high risk (≥50% major morbidity or mortality) for reoperative surgery were prospectively enrolled in the multicenter PARTNER (Placement of Aortic Transcatheter Valves) 2 valve-in-valve and continued access registries. Three-year clinical and echocardiographic follow-up was obtained. RESULTS: Valve-in-valve procedures were performed in 365 patients. The mean age was 78.9 ± 10.2 years, and the mean Society of Thoracic Surgeons score was 9.1 ± 4.7%. At 3 years, the overall Kaplan-Meier estimate of all-cause mortality was 32.7%. Aortic valve re-replacement was required in 1.9%. Mean transaortic gradient was 35.0 mm Hg at baseline, decreasing to 17.8 mm Hg at 30-day follow-up and 16.6 mm Hg at 3-year follow-up. Baseline effective orifice area was 0.93 cm2, increasing to 1.13 and 1.15 cm2 at 30 days and 3 years, respectively. Moderate to severe aortic regurgitation was reduced from 45.1% at pre-TAVR baseline to 2.5% at 3 years. Importantly, moderate or severe mitral and tricuspid regurgitation also decreased (33.7% vs. 8.6% [p < 0.0001] and 29.7% vs. 18.8% [p = 0.002], respectively). Baseline left ventricular ejection fraction was 50.7%, increasing to 54.7% at 3 years (p < 0.0001), while left ventricular mass index was 136.4 g/m2, decreasing to 109.1 g/m2 at 3 years (p < 0.0001). New York Heart Association functional class improved, with 90.4% in class III or IV at baseline and 14.1% at 3 years (p < 0.0001), and Kansas City Cardiomyopathy Questionnaire overall score increased (43.1 to 73.1; p < 0.0001). CONCLUSIONS: At 3-year follow-up, TAVR for bioprosthetic aortic valve failure was associated with favorable survival, sustained improved hemodynamic status, and excellent functional and quality-of-life outcomes. (The PARTNER II Trial: Placement of Aortic Transcatheter Valves II - PARTNER II - Nested Registry 3/Valve-in-Valve [PII NR3/ViV]; NCT03225001).

Long-Term Implications of Atrial Fibrillation in Patients With Degenerative Mitral Regurgitation.

BACKGROUND: Scientific guidelines consider atrial fibrillation (AF) complicating degenerative mitral regurgitation (DMR) a debated indication for surgery. OBJECTIVES: This study analyzed the prognostic/therapeutic implications of AF at DMR diagnosis and long-term. METHODS: Patients were enrolled in the MIDA (Mitral Regurgitation International Database) registry, which reported the consecutive, multicenter, international experience with DMR due to flail leaflets echocardiographically diagnosed. RESULTS: Among 2,425 patients (age 67 ± 13 years; 71% male, 67% asymptomatic, ejection fraction 64 ± 10%), 1,646 presented at diagnosis with sinus rhythm (SR), 317 with paroxysmal AD, and 462 with persistent AF. Underlying clinical/instrumental characteristics progressively worsened from SR to paroxysmal to persistent AF. During follow-up, paroxysmal and persistent AF were associated with excess mortality (10-year survival in SR and in paroxysmal and persistent AF was 74 ± 1%, 59 ± 3%, and 46 ± 2%, respectively; p < 0.0001), that persisted 20 years post-diagnosis and independently of all baseline characteristics (p values <0.0001). Surgery (n = 1,889, repair 88%) was associated with better survival versus medical management, regardless of all baseline characteristics and rhythm (adjusted hazard ratio: 0.26; 95% confidence interval: 0.23 to 0.30; p < 0.0001) but post-surgical outcome remained affected by AF (10-year post-surgical survival in SR and in paroxysmal and persistent AF was 82 ± 1%, 70 ± 4%, and 57 ± 3%, respectively; p < 0.0001). CONCLUSIONS: AF is a frequent occurrence at DMR diagnosis. Although AF is associated with older age and more severe presentation of DMR, it is independently associated with excess mortality long-term after diagnosis. Surgery is followed by improved survival in each cardiac rhythm subset, but persistence of excess risk is observed for each type of AF. Our study indicates that detection of AF, even paroxysmal, should trigger prompt consideration for surgery.

Coexistent bicuspid aortic valve and mitral valve prolapse: epidemiology, phenotypic spectrum, and clinical implications.

AIMS: Bicuspid aortic valve (BAV) and mitral valve prolapse (MVP) are common but the prevalence and significance of coexistent conditions are unknown. This study investigated the prevalence, phenotypic expression, and clinical significance of coexistent MVP-BAV. METHODS AND RESULTS: Retrospective comparison of MVP-BAV and MVP-tricuspid aortic valve (TAV) prevalence including de novo echocardiographic analysis of all MVP-BAV patients between 2005 and 2015 was performed. The community prevalence of MVP-BAV was 2.7% vs. 3.4% for MVP-TAV (P = 0.45). Posterior mitral leaflet (PML)-MVP was the most common phenotype in both BAV and TAV (P = 0.38), but anterior mitral leaflet (AML)-MVP was twice more prevalent in BAV (31% vs. 15%, P < 0.0001). Among 130 subjects with coexistent MVP-BAV (81% men, 51 ± 16 years old), 31 (24%) exhibited AML:PML length ratio ≥3:1, termed large-AML prolapse (LAP-BAV), who had predominant BAV regurgitation when compared with those with non-LAP-BAV (P ≤ 0.001). An extreme phenotype of LAP-BAV with giant-AML prolapse and diminutive PML (GAP-BAV) was identified in 18/130 (14%) subjects. Compared with posterior-MVP-BAV, GAP-BAV patients were younger (42 ± 15 vs. 64 ± 12 years, P < 0.0001), had larger aortic annulus (28 ± 3 vs. 26 ± 2 mm, P = 0.01), and 61% had ≥ moderate BAV regurgitation (vs. 16%, P = 0.0007). Mitral repair occurred in 37/130 (28%) subjects. After median follow-up 5.5 months (4-83), 4/5 (80%) GAP-BAV patients required redo surgery for recurrent mitral regurgitation vs. 2/31 (6%) for non-LAP-BAV (P = 0.001). CONCLUSION: The community prevalence of coexistent MVP-BAV is comparable to MVP-TAV and their most common phenotype is posterior-MVP. However, anterior-MVP is twice as prevalent in MVP-BAV. A large-AML phenotype (LAP-BAV) with predominant BAV regurgitation affects 24% of MVP-BAV patients. An extreme phenotype of anterior-MVP (GAP-BAV) affects 14% of BAV patients; characterized by exceptionally large AML, diminutive PML, high mitral and aortic regurgitation prevalence, and high mitral repair failure rate.