Patient-Prosthesis Mismatch After Surgical Aortic Valve Replacement: Analysis of the PARTNER Trials.

BACKGROUND: Our objective was to compare the impact of patient-prosthesis mismatch (PPM) for 2 years after surgical aortic valve replacement within the prospective, randomized Placement of Aortic Transcatheter Valves (PARTNER) trials. METHODS: Surgical aortic valve replacement patients from the PARTNER 1, 2, and 3 trials were included. PPM was classified as moderate (indexed effective orifice area ≤0.85 cm2/m2) or severe (indexed effective orifice area ≤0.65 cm2/m2). The primary endpoint was the composite of all-cause death and heart failure rehospitalization at 2 years. RESULTS: By the predicted PPM method (PPMP), 59.1% had no PPM, 38.8% moderate PPM, and 2.1% severe PPM; whereas by the measured PPM method (PPMM), 42.4% had no PPM, 36.0% moderate, and 21.6% severe. Patients with no PPMP (23.6%) had a lower rate of the primary endpoint compared with patients with moderate (28.2%, P = .03) or severe PPMP (38.8%, P = .02). Using the PPMM method, there was no difference between the no (17.7%) and moderate PPMM groups (21.1%) in the primary outcome (P = .16). However, those with no PPMM or moderate PPMM were improved compared with severe PPMM (27.4%, P < .001 and P = .02, respectively). CONCLUSIONS: Severe PPM analyzed by PPMP was only 2.1% for surgical aortic valve replacement patients. The PPMM method overestimated the incidence of severe PPM relative to PPMP, but was also associated with worse outcome. There was higher all-cause mortality in patients with severe PPM, thus surgical techniques to minimize PPM remain critical.

1-Year Outcomes of Cardioband Tricuspid Valve Reconstruction System Early Feasibility Study.

BACKGROUND: Tricuspid regurgitation (TR) is prevalent and undertreated, with mortality and morbidity increasing with TR severity. Given poor outcomes with medical therapy and high in-hospital mortality for isolated tricuspid valve surgery, emerging transcatheter repair devices offer a promising alternative. OBJECTIVES: The Edwards Cardioband Tricuspid Valve Reconstruction System Early Feasibility study (NCT03382457) evaluates the treatment of functional TR via annular reduction with the Cardioband Tricuspid Valve Reconstruction System (Edwards Lifesciences). METHODS: Patients with ≥ moderate functional TR were eligible for this prospective, single-arm multicenter study. At 1 year, patients were evaluated for echocardiographic parameters, clinical and quality-of-life measures, and major adverse events. RESULTS: The 37 patients enrolled had a mean age of 78 years; 76% were female; and they had ≥ severe functional (97.3%) or mixed (2.7%) TR, atrial flutter/fibrillation (97%), and New York Heart Association functional class III/IV (65%). At 1 year, 73.0% achieved ≤ moderate TR (P < 0.0001), and 73.1% had ≥2 grade reductions. Echocardiography showed significant reductions in the tricuspid annulus diameter (P < 0.0001), mean vena contracta (P < 0.0001), proximal isovelocity surface area effective regurgitant orifice area (P < 0.0001), right ventricular end-diastolic diameter (P < 0.0001), and inferior vena contracta (P = 0.0006). New York Heart Association functional class improved significantly (P < 0.0001), with 92.3% achieving class I/II, and Kansas City Cardiomyopathy Questionnaire scores improved by 19.0 points (P < 0.0001). One-year cardiovascular mortality was 8.1%, reinterventions were necessary in 5.4%, major access site complications occurred in 8.1%, and severe bleeding was noted in 35.1% of patients. Kaplan-Meier estimates of survival and freedom from heart failure rehospitalization were 85.9% and 88.7%, respectively. CONCLUSIONS: One-year experience using the Cardioband system for tricuspid valve repair shows high survival and low rehospitalization rates with durable outcomes in TR reduction and echocardiographic, clinical, and quality-of-life outcomes.

Transcatheter Edge-to-Edge Repair for Treatment of Tricuspid Regurgitation.

BACKGROUND: Tricuspid regurgitation (TR) is a frequent disease with a progressive increase in mortality as disease severity increases. Transcatheter therapies for treatment of TR may offer a safe and effective alternative to surgery in this high-risk population. OBJECTIVES: The purpose of this report was to study the 1-year outcomes with the TriClip transcatheter tricuspid valve repair system, including repair durability, clinical benefit and safety. METHODS: The TRILUMINATE trial (n = 85) is an international, prospective, single arm, multicenter study investigating safety and performance of the TriClip Tricuspid Valve Repair System in patients with moderate or greater TR. Echocardiographic assessment was performed by a core laboratory. RESULTS: At 1 year, TR was reduced to moderate or less in 71% of subjects compared with 8% at baseline (p < 0.0001). Patients experienced significant clinical improvements in New York Heart Association (NYHA) functional class I/II (31% to 83%, p < 0.0001), 6-minute walk test (272.3 ± 15.6 to 303.2 ± 15.6 meters, p = 0.0023) and Kansas City Cardiomyopathy Questionnaire (KCCQ) score (improvement of 20 ± 2.61 points, p < 0.0001). Significant reverse right ventricular remodeling was observed in terms of size and function. The overall major adverse event rate and all-cause mortality were both 7.1% at 1 year. CONCLUSION: Transcatheter tricuspid valve repair using the TriClip device was found to be safe and effective in patients with moderate or greater TR. The repair itself was durable at reducing TR at 1 year and was associated with a sustained and marked clinical benefit with low mortality after 1 year in a fragile population that was at high surgical risk. (TRILUMINATE Study With Abbott Transcatheter Clip Repair System in Patients With Moderate or Greater TR; NCT03227757).

Association of Bioprosthetic Aortic Valve Leaflet Calcification on Hemodynamic and Clinical Outcomes.

BACKGROUND: The prognostic value of aortic valve calcification (AVC) measured by using multidetector computed tomography imaging has been well validated in native aortic stenosis, and sex-specific thresholds have been proposed. However, few data are available regarding the impact of leaflet calcification on outcomes after biological aortic valve replacement (AVR). OBJECTIVES: The goal of this study was to analyze the association of quantitative bioprosthetic leaflet AVC with hemodynamic and clinical outcomes, as well as its possible interaction with sex. METHODS: From 2008 to 2010, a total of 204 patients were prospectively enrolled with a median of 7.0 years (interquartile range: 5.1 to 9.2 years) after biological surgical AVR. AVC measured by using the Agatston method was indexed to the cross-sectional area of aortic annulus measured by echocardiography to calculate the AVC density (AVCd). Presence of hemodynamic valve deterioration (HVD; increase in mean gradient [MG] ≥10 mm Hg and/or increase in transprosthetic regurgitation ≥1) was assessed by echocardiography in 137 patients at the 3-year follow-up. The primary clinical endpoint was mortality or aortic valve re-intervention. RESULTS: There was no significant sex-related difference in the relationship between bioprosthetic AVCd and the progression of MG. Baseline AVCd showed an independent association with HVD at 3 years. During follow-up, there were 134 (65.7%) deaths (n = 100) or valve re-interventions (n = 47). AVCd ≥58 AU/cm2 was independently associated with an increased risk of mortality or aortic valve re-intervention (adjusted hazard ratio: 2.23; 95% confidence interval: 1.44 to 3.35; p < 0.001). The AVCd threshold combined with an MG progression threshold of 10 mm Hg amplified the stratification of patients at risk (log-rank, p < 0.001). The addition of AVCd threshold into the prediction model including traditional risk factors improved outcome prediction (net classification improvement: 0.25, p = 0.04; likelihood ratio test, p < 0.001). CONCLUSIONS: Aortic bioprosthetic leaflet calcification is strongly and independently associated with HVD and the risk of death or aortic valve re-intervention. As opposed to native aortic stenosis, there is no sex-related differences in the relationship between AVCd and hemodynamic or clinical outcomes.

Transcatheter edge-to-edge repair for reduction of tricuspid regurgitation: 6-month outcomes of the TRILUMINATE single-arm study.

BACKGROUND: Tricuspid regurgitation is a prevalent disease associated with high morbidity and mortality, with few treatment options. The aim of the TRILUMINATE trial is to evaluate the safety and effectiveness of TriClip, a minimally invasive transcatheter tricuspid valve repair system, for reducing tricuspid regurgitation. METHODS: The TRILUMINATE trial is a prospective, multicentre, single-arm study in 21 sites in Europe and the USA. Patients with moderate or greater triscuspid regurgitation, New York Heart Association class II or higher, and who were adequately treated per applicable standards were eligible for enrolment. Patients were excluded if they had systolic pulmonary artery pressure of more than 60 mm Hg, a previous tricuspid valve procedure, or a cardiovascular implantable electronic device that would inhibit TriClip placement. Participants were treated using a clip-based edge-to-edge repair technique with the TriClip tricuspid valve repair system. Tricuspid regurgitation was graded using a five-class grading scheme (mild, moderate, severe, massive, and torrential) that expanded on the standard American Society of Echocardiography grading scheme. The primary efficacy endpoint was a reduction in tricuspid regurgitation severity by at least one grade at 30 days post procedure, with a performance goal of 35%, analysed in all patients who had an attempted tricuspid valve repair procedure upon femoral vein puncture. The primary safety endpoint was a composite of major adverse events at 6 months, with a performance goal of 39%. Patients were excluded from the primary safety analysis if they did not reach 6-month follow-up and did not have a major adverse event during previous follow-ups. The trial has completed enrolment and follow-up is ongoing; it is registered with ClinicalTrials.gov, number NCT03227757. FINDINGS: Between Aug 1, 2017, and Nov 29, 2018, 85 patients (mean age 77·8 years [SD 7·9]; 56 [66%] women) were enrolled and underwent successful TriClip implantation. Tricuspid regurgitation severity was reduced by at least one grade at 30 days in 71 (86%) of 83 patients who had available echocardiogram data and imaging. The one-sided lower 97·5% confidence limit was 76%, which was greater than the prespecified performance goal of 35% (p<0·0001). One patient withdrew before 6-month follow-up without having had a major adverse event and was excluded from analysis of the primary safety endpoint. At 6 months, three (4%) of 84 patients experienced a major adverse event, which was less than the prespecified performance goal of 39% (p<0·0001). Single leaflet attachment occurred in five (7%) of 72 patients. No periprocedural deaths, conversions to surgery, device embolisations, myocardial infarctions, or strokes occurred. At 6 months, all-cause mortality had occurred in four (5%) of 84 patients. INTERPRETATION: The TriClip system appears to be safe and effective at reducing tricuspid regurgitation by at least one grade. This reduction could translate to significant clinical improvement at 6 months post procedure. FUNDING: Abbott.

Metabolic Syndrome Exacerbates Pulmonary Hypertension due to Left Heart Disease.

RATIONALE: Pulmonary hypertension (PH) due to left heart disease (LHD), or group 2 PH, is the most prevalent form of PH worldwide. PH due to LHD is often associated with metabolic syndrome (MetS). In 12% to 13% of cases, patients with PH due to LHD display vascular remodeling of pulmonary arteries (PAs) associated with poor prognosis. Unfortunately, the underlying mechanisms remain unknown; PH-targeted therapies for this group are nonexistent, and the development of a new preclinical model is crucial. Among the numerous pathways dysregulated in MetS, inflammation plays also a critical role in both PH and vascular remodeling. OBJECTIVE: We hypothesized that MetS and inflammation may trigger the development of vascular remodeling in group 2 PH. METHODS AND RESULTS: Using supracoronary aortic banding, we induced diastolic dysfunction in rats. Then we induced MetS by a combination of high-fat diet and olanzapine treatment. We used metformin treatment and anti-IL-6 (interleukin-6) antibodies to inhibit the IL-6 pathway. Compared with sham conditions, only supracoronary aortic banding+MetS rats developed precapillary PH, as measured by both echocardiography and right/left heart catheterization. PH in supracoronary aortic banding+MetS was associated with macrophage accumulation and increased IL-6 production in lung. PH was also associated with STAT3 (signal transducer and activator of transcription 3) activation and increased proliferation of PA smooth muscle cells, which contributes to remodeling of distal PA. We reported macrophage accumulation, increased IL-6 levels, and STAT3 activation in the lung of group 2 PH patients. In vitro, IL-6 activates STAT3 and induces human PA smooth muscle cell proliferation. Metformin treatment decreased inflammation, IL-6 levels, STAT3 activation, and human PA smooth muscle cell proliferation. In vivo, in the supracoronary aortic banding+MetS animals, reducing IL-6, either by anti-IL-6 antibody or metformin treatment, reversed pulmonary vascular remodeling and improve PH due to LHD. CONCLUSIONS: We developed a new preclinical model of group 2 PH by combining MetS with LHD. We showed that MetS exacerbates group 2 PH. We provided evidence for the importance of the IL-6-STAT3 pathway in our experimental model of group 2 PH and human patients.

Activated platelets promote an osteogenic programme and the progression of calcific aortic valve stenosis.

AIMS: Calcific aortic valve stenosis (CAVS) is characterized by a fibrocalcific process. Studies have shown an association between CAVS and the activation of platelets. It is believed that shear stress associated with CAVS promotes the activation of platelets. However, whether platelets actively participate to the mineralization of the aortic valve (AV) and the progression of CAVS is presently unknown. To identify the role of platelets into the pathobiology of CAVS. METHODS AND RESULTS: Explanted control non-mineralized and mineralized AVs were examined by scanning electron microscope (SEM) for the presence of activated platelets. In-depth functional assays were carried out with isolated human valve interstitial cells (VICs) and platelets as well as in LDLR-/- apoB100/100 IGFII (IGFII) mice. Scanning electron microscope and immunogold markings for glycoprotein IIb/IIIa (GPIIb/IIIa) revealed the presence of platelet aggregates with fibrin in endothelium-denuded areas of CAVS. In isolated VICs, collagen-activated platelets induced an osteogenic programme. Platelet-derived adenosine diphosphate induced the release of autotaxin (ATX) by VICs. The binding of ATX to GPIIb/IIIa of platelets generated lysophosphatidic acid (LysoPA) with pro-osteogenic properties. In IGFII mice with CAVS, platelet aggregates were found at the surface of AVs. Administration of activated platelets to IGFII mice accelerated the development of CAVS by 2.1-fold, whereas a treatment with Ki16425, an antagonist of LysoPA receptors, prevented platelet-induced mineralization of the AV and the progression of CAVS. CONCLUSIONS: These findings suggest a novel role for platelets in the progression of CAVS.

Multimarker Approach to Identify Patients With Higher Mortality and Rehospitalization Rate After Surgical Aortic Valve Replacement for Aortic Stenosis.

OBJECTIVES: This study sought to evaluate whether a multimarker approach might identify patients with higher mortality and hospitalization rates after aortic valve replacement (AVR) for aortic stenosis (AS). BACKGROUND: The society valve guidelines include accepted triggers for AVR in patients with severe asymptomatic AS, but circulating biomarkers do not have a clear role. METHOD: From a prospective registry of patients undergoing cardiac surgery between 2000 and 2012, 665 treated with surgical AVR (441 isolated) were evaluated. Seven biomarkers were measured on blood samples obtained before AVR. Biomarker levels were adjusted to account for the influence of age, sex, body mass index, and renal function; the median was used to determine an elevated value. Endpoints included all-cause mortality and all-cause and cardiovascular hospitalizations. Mean follow-up was 10.7 years and 299 (45%) died. RESULTS: Patients with 0 to 1, 2 to 3, 4 to 6, and 7 biomarkers elevated had 5-year mortality of 10%, 12%, 24%, and 33%, respectively, and 10-year mortality of 24%, 35%, 58%, and 71%, respectively (log-rank p < 0.001). The association between an increasing number of elevated biomarkers and increased all-cause mortality was observed among those with minimal symptoms (New York Heart Association functional class I or II) and those with a low N-terminal pro-B-type natriuretic peptide (p < 0.01 for both). Compared with those with 0 to 1 biomarkers elevated, patients with 4 to 6 or 7 biomarkers elevated had an increased hazard of mortality after adjustment for clinical risk scores (p < 0.01) and a 2- to 3-fold higher rate of all-cause and cardiovascular rehospitalization after AVR. Similar findings were obtained when evaluating cardiovascular mortality. Among patients with no or minimal symptoms, 42% had ≥4 biomarkers elevated. CONCLUSIONS: Among patients with severe AS treated with surgical AVR, an increasing number of elevated biomarkers of cardiovascular stress was associated with higher all-cause and cardiovascular mortality and a higher rate of repeat hospitalization. A multimarker approach may be useful in the surveillance of asymptomatic patients with severe AS to optimize surgical timing.

Hemodynamic Deterioration of Surgically Implanted Bioprosthetic Aortic Valves.

BACKGROUND: Dysmetabolic profile has been associated with native aortic valve stenosis. However, there are limited data on the effects of an atherogenic milieu and its potential implications on the structural and hemodynamic deterioration of aortic bioprosthetic valves. OBJECTIVES: This prospective longitudinal study sought to determine the predictors and impact on outcomes of hemodynamic valve deterioration (HVD) of surgically implanted aortic bioprostheses. METHODS: A total of 137 patients with an aortic bioprosthesis implanted for a median time of 6.7 (interquartile range: 5.1 to 9.1) years prospectively underwent a first (baseline) assessment with complete Doppler echocardiography, quantitation of bioprosthesis leaflet calcification by multidetector computed tomography (CT), and a fasting blood sample to assess cardiometabolic risk profile. All patients underwent a second (follow-up) Doppler echocardiography examination at 3 (interquartile range: 2.9 to 3.3) years post-baseline visit. HVD was defined by an annualized change in mean transprosthetic gradient ≥3 mm Hg/year and/or worsening or transprosthetic regurgitation by ≥1/3 class. The primary endpoint was a nonhierarchical composite of death from any cause or aortic reintervention procedure (redo surgical valve replacement or transcatheter valve-in-valve implantation) for bioprosthesis failure. RESULTS: Thirty-four patients (25.6%) had leaflet calcification on baseline CT, and 18 patients (13.1%) developed an HVD between baseline and follow-up echocardiography. Fifty-two patients (38.0%) met the primary endpoint during subsequent follow-up after the second echocardiographic examination. Leaflet calcification (hazard ratio [HR]: 2.58; 95% confidence interval [CI]: 1.35 to 4.82; p = 0.005) and HVD (HR: 5.12; 95% CI: 2.57 to 9.71; p < 0.001) were independent predictors of the primary endpoint. Leaflet calcification, insulin resistance (homeostatic model assessment index ≥2.7), lipoprotein-associated phospholipase A2 activity (Lp-PLA2 per 0.1 nmol/min/ml increase), and high level of proprotein convertase subtilisin/kexin 9 (PCSK9) (≥305 ng/ml) were associated with the development of HVD after adjusting for age, sex, and time interval since aortic valve replacement. CONCLUSIONS: HVD identified by Doppler echocardiography is independently associated with a marked increase in the risk of valve reintervention or mortality in patients with a surgical aortic bioprosthesis. A dysmetabolic profile characterized by elevated plasma Lp-PLA2, PCSK9, and homeostatic model assessment index was associated with increased risk of HVD. The presence of leaflet calcification as detected by CT was a strong predictor of HVD, providing incremental risk-predictive capacity.

Forward Left Ventricular Ejection Fraction: A Simple Risk Marker in Patients With Primary Mitral Regurgitation.

BACKGROUND: The timing of mitral valve surgery in asymptomatic patients with primary mitral regurgitation (MR) is controversial. We hypothesized that the forward left ventricular (LV) ejection fraction (LVEF; ie, LV outflow tract stroke volume divided by LV end-diastolic volume) is superior to the total LVEF to predict outcomes in MR. The objective of this study was to examine the association between echocardiographic parameters of MR severity and LV function and outcomes in patients with MR. METHODS AND RESULTS: The clinical and Doppler-echocardiographic data of 278 patients with ≥mild MR and no class I indication of mitral valve surgery at baseline were retrospectively analyzed. The primary study end point was the composite of mitral valve surgery or death. During a mean follow-up of 5.4±3.2 years, there were 147 (53%) events: 96 (35%) MV surgeries and 66 (24%) deaths. Total LVEF and global longitudinal strain were not associated with the occurrence of events, whereas forward LVEF (P<0.0001) and LV end-systolic diameter (P=0.0003) were. After adjustment for age, sex, MR severity, Charlson probability, coronary artery disease, and atrial fibrillation, forward LVEF remained independently associated with the occurrence of events (adjusted hazard ratio: 1.09, [95% confidence interval]: 1.02-1.17 per 5% decrease; P=0.01), whereas LV end-systolic diameter was not (P=0.48). CONCLUSIONS: The results of this study suggest that the forward LVEF may be superior to the total LVEF and LV end-systolic diameter to predict outcomes in patients with primary MR. This simple and easily measurable parameter may be useful to improve risk stratification and select the best timing for intervention in patients with primary MR.

OxLDL-derived lysophosphatidic acid promotes the progression of aortic valve stenosis through a LPAR1-RhoA-NF-κB pathway.

AIMS: Oxidatively modified lipoproteins may promote the development/progression of calcific aortic valve stenosis (CAVS). Oxidative transformation of low-density lipoprotein (OxLDL) generates lysophosphatidic acid (LPA), a lipid mediator that accumulates in mineralized aortic valves. LPA activates at least six different G protein-coupled receptors, which may play a role in the pathophysiology of CAVS. We hypothesized that LPA derived from OxLDL may promote a NF-κB signature that drives osteogenesis in the aortic valve. METHODS AND RESULTS: The role of OxLDL-LPA was examined in isolated valve interstitial cells (VICs) and the molecular pathway was validated in human explanted aortic valves and in a mouse model of CAVS. We found that OxLDL-LPA promoted the mineralization and osteogenic transition of VICs through LPAR1 and the activation of a RhoA-NF-κB pathway. Specifically, we identified that RhoA/ROCK activated IκB kinase alpha, which promoted the phosphorylation of p65 on serine 536 (p65 pS536). p65 pS536 was recruited to the BMP2 promoter and directed an osteogenic program not responsive to the control exerted by the inhibitor of kappa B. In LDLR-/-/ApoB100/100/IGFII transgenic mice (IGFII), which develop CAVS under a high-fat and high-sucrose diet the administration of Ki16425, a Lpar1 blocker, reduced by three-fold the progression rate of CAVS and also decreased the osteogenic activity as measured with a near-infrared fluorescent probe that recognizes hydroxyapatite of calcium. CONCLUSIONS: OxLDL-LPA promotes an osteogenic program in the aortic valve through a LPAR1-RhoA/ROCK-p65 pS536 pathway. LPAR1 may represent a suitable target to prevent the progression of CAVS.

Systolic hypertension and progression of aortic valve calcification in patients with aortic stenosis: results from the PROGRESSA study.

AIMS: Hypertension is highly prevalent in patients with aortic stenosis (AS) and is associated with worse outcomes. The current prospective study assessed the impact of systolic hypertension (SHPT) on the progression of aortic valve calcification (AVC) measured by multidetector computed tomography (MDCT) in patients with AS. METHODS AND RESULTS: The present analysis includes the first series of 101 patients with AS prospectively recruited in the PROGRESSA study. Patients underwent comprehensive Doppler echocardiography and MDCT exams at baseline and after 2-year follow-up. AVC and coronary artery calcification (CAC) were measured using the Agatston method. Patients with SHPT at baseline (i.e. systolic blood pressure ≥140 mmHg; n = 37, 37%) had faster 2-year AVC progression compared with those without SHPT (i.e. systolic blood pressure <140 mmHg) (AVC median [25th percentile-75th percentile]: +370 [126-824] vs. +157 [58-303] AU; P = 0.007, respectively). Similar results were obtained with the analysis of AVC progression divided by the cross-sectional area of the aortic annulus (AVCdensity: +96 [34-218] vs. +45 [14-82] AU/cm2, P = 0.01, respectively). In multivariable analysis, SHPT remained significantly associated with faster progression of AVC or AVCdensity (all P = 0.001). There was no significant difference between groups with respect to progression of CAC (+39 [3-199] vs. +41 [0-156] AU, P = 0.88). CONCLUSION: This prospective study shows for the first time that SHPT is associated with faster AVC progression but not with CAC progression in AS patients. These findings provide further support for the elaboration of randomized clinical trials to assess the efficacy of antihypertensive medication to slow the stenosis progression in patients with AS.

Discordant Grading of Aortic Stenosis Severity: Echocardiographic Predictors of Survival Benefit Associated With Aortic Valve Replacement.

OBJECTIVES: This study sought to assess the survival benefit associated with aortic valve replacement (AVR) according to different strata of echocardiographic parameters of aortic stenosis (AS) severity, and especially in patients with an aortic valve area (AVA) comprised between 0.8 cm(2) and 1 cm(2). BACKGROUND: Discordant findings between AVA (≤1.0 cm(2)) and mean gradient (MG) (<40 mm Hg) raise uncertainty regarding the actual severity of AS. Some studies suggested that the AVA threshold value to define severe AS should be decreased to 0.8 cm(2) to reconcile these discordances. METHODS: A total of 1,710 patients with documented moderate to severe AS by Doppler echocardiography were separated into 4 strata of AS severity based alternatively on AVA, indexed AVA, MG, or peak aortic jet velocity (Vpeak). We compared the survival rates of medically versus surgically treated patients. To eliminate covariate differences that may lead to biased estimates of treatment effect, a propensity matching with a greedy 5-to-1 digit-matching algorithm was used. RESULTS: Mean AVA was 0.9 ± 0.3 cm(2), mean MG 33 ± 18 mm Hg, and mean Vpeak 3.6 ± 0.9 m/s. A total of 1,030 (60%) patients underwent AVR within 3 months following echocardiographic evaluation. During a mean follow-up of 4.4 ± 3.0 years there were 469 deaths. Patients with an AVA between 0.8 cm(2) and 1.0 cm(2) had a significant observed survival benefit with AVR (hazard ratio: 0.37 [95% confidence interval: 0.21 to 0.63]; p = 0.0002). AVR was also associated with improved survival in patients with MG between 25 mm Hg and 40 mm Hg or Vpeak between 3 m/s and 4 m/s, but only in patients with concomitant AVA ≤1 cm(2) (p = 0.001 vs. p = 0.46 in patients with AVA >1 cm(2)). CONCLUSIONS: These results do not support decreasing the AVA threshold value for severity to 0.8 cm(2) and they confirm that AVR is associated with improved survival in a substantial number of patients with discordant aortic grading.

Myocardial Injury After Transaortic Versus Transapical Transcatheter Aortic Valve Replacement.

BACKGROUND: The release of cardiac biomarkers of myocardial injury after transcatheter aortic valve replacement (TAVR) is common, but no data exist on patients undergoing TAVR through a transaortic approach. We aimed to evaluate the incidence and prognostic significance of the increase in cardiac biomarkers in nontransfemoral TAVR candidates, comparing transaortic and transapical approaches. METHODS: After excluding patients deemed suitable for transfemoral TAVR, 251 consecutive patients (transaortic, 45; transapical, 206) were prospectively evaluated. Creatine kinase-myocardial band and cardiac troponin T levels were measured at baseline and at 6, 12, 24, 48, and 72 hours after TAVR. Baseline and 6- to 12-month echocardiographic and clinical follow-up were performed. RESULTS: After TAVR, cardiac troponin T increased above the upper normal values in all patients (peak value 0.64 µg/L [IQR, 0.39 to 1.03 µg/L]), whereas creatine kinase-myocardial band levels increased in 88% of patients (transaortic 51%, transapical 96%, p < 0.001; peak value 20.1 µg/L [interquartile range, 14.3 to 31.6 µg/L]). Compared with the transaortic approach, the transapical approach was associated with a greater rise in both cardiac biomarkers (p < 0.001 for both), and a lesser improvement in left ventricular ejection fraction (p = 0.058) and global longitudinal strain (p = 0.039) at 6- to 12-month follow-up. Greater increases of cardiac troponin T levels were independently associated with 30-day and 1-year overall and cardiovascular mortality (p < 0.001 for all). A 15-fold rise in cardiac troponin T levels was the optimal threshold for determining poorer outcomes (p < 0.001). CONCLUSIONS: Periprocedural TAVR-related myocardial injury in nontransfemoral candidates was demonstrated in all patients, but the transapical approach was associated with significantly greater myocardial injury compared with the transaortic approach. A higher degree of myocardial injury translated into reduced left ventricular function improvement and lower early and midterm survival rates.

Impact of classic and paradoxical low flow on survival after aortic valve replacement for severe aortic stenosis.

BACKGROUND: Low flow (LF) can occur with reduced (classic) or preserved (paradoxical) left ventricular ejection fraction (LVEF). OBJECTIVES: The objective of this study was to compare outcomes of patients with low ejection fraction (LEF), paradoxical low flow (PLF), and normal flow (NF) after aortic valve replacement (AVR). METHODS: We examined 1,154 patients with severe aortic stenosis (AS) who underwent AVR with or without coronary artery bypass grafting. RESULTS: Among these patients, 206 (18%) had LEF as defined by LVEF of <50%; 319 (28%) had PLF as defined by LVEF of ≥50% but stroke volume indexed to body surface area (SVi) of ≤35 ml ∙ m(-2); and 629 (54%) had NF, as defined by LVEF of ≥50% and SVi of >35 ml ∙ m(2). Aortic valve area was lower in low flow/LVEF groups (LEF: 0.71 ± 0.20 cm(2) and PLF: 0.65 ± 0.23 cm(2) vs. NF: 0.77 ± 0.18 cm(2); p < 0.001). The 30-day mortality was higher (p < 0.001) in LEF and PLF groups than in the NF group (6.3% and 6.3% vs. 1.8%, respectively). SVi and PLF group were independent predictors of operative mortality (odds ratio [OR]: 1.18, p < 0.05; and OR: 2.97, p = 0.004; respectively). At 5 years after AVR, overall survival was 72 ± 4% in LEF group, 81 ± 2% in PLF group, and 85 ± 2% in NF group (p < 0.0001). CONCLUSIONS: Patients with LEF or PLF AS have a higher operative risk, but pre-operative risk score accounted only for LEF and lower LVEF. Patients with LEF had the worst survival outcome, whereas patients with PLF and normal flow had similar survival rates after AVR. As a major predictor of perioperative mortality, SVi should be integrated in AS patients' pre-operative evaluation.