Do postoperative hemodynamic parameters add prognostic value for mortality after surgical aortic valve replacement?

Background: Although various hemodynamic parameters to assess prosthetic performance are available, prosthesis-patient mismatch (PPM) is defined exclusively by effective orifice area (EOA) index thresholds. Adjusting for the Society of Thoracic Surgeons predicted risk of mortality (STS PROM), we aimed to explore the added value of postoperative hemodynamic parameters for the prediction of all-cause mortality at 5 years after aortic valve replacement. Methods: Data were obtained from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial, a multicenter prospective cohort study examining the performance of the Avalus bioprosthesis. Candidate predictors were assessed at the first follow-up visit; patients who had no echocardiography data, withdrew consent, or died before this visit were excluded. Candidate predictors included peak jet velocity, mean pressure gradient, EOA, predicted and measured EOA index, Doppler velocity index, indexed internal prosthesis orifice area, and categories for PPM. The performance of Cox models was investigated using the c-statistic and net reclassification improvement (NRI), among other tools. Results: A total of 1118 patients received the study valve, of whom 1022 were eligible for the present analysis. In univariable analysis, STS PROM was the sole significant predictor of all-cause mortality (hazard ratio, 1.40; 95% confidence interval, 1.26-1.55). When extending the STS PROM with single hemodynamic parameters, neither the c-statistics nor the NRIs demonstrated added prognostic value compared to a model with STS PROM alone. Similar findings were observed when multiple hemodynamic parameters were added. Conclusions: The STS PROM was found to be the main predictor of patient prognosis. The additional prognostic value of postoperative hemodynamic parameters for the prediction of all-cause mortality was limited.

Improving accuracy in diagnosing aortic stenosis severity: An in-depth analysis of echocardiographic measurement error through literature review and simulation study.

AIMS: The present guidelines advise replacing the aortic valve for individuals with severe aortic stenosis (AS) based on various echocardiographic parameters. Accurate measurements are essential to avoid misclassification and unnecessary interventions. The objective of this study was to evaluate the influence of measurement error on the echocardiographic evaluation of the severity of AS. METHODS AND RESULTS: A systematic review was performed to examine whether measurement errors are reported in studies focusing on the prognostic value of peak aortic jet velocity (Vmax ), mean pressure gradient (MPG), and effective orifice area (EOA) in asymptomatic patients with AS. Out of the 37 studies reviewed, 17 (46%) acknowledged the existence of measurement errors, but none of them utilized methods to address them. Secondly, the magnitude of potential errors was collected from available literature for use in clinical simulations. Interobserver variability ranged between 0.9% and 8.3% for Vmax and MPG but was higher for EOA (range 7.7%-12.7%), indicating lower reliability. Assuming a circular left ventricular outflow tract area led to a median underestimation of EOA by 23% compared to planimetry by other modalities. A clinical simulation resulted in the reclassification of 42% of patients, shifting them from a diagnosis of severe AS to moderate AS. CONCLUSIONS: Measurement errors are underreported in studies on echocardiographic assessment of AS severity. These errors can lead to misclassification and misdiagnosis. Clinicians and scientists should be aware of the implications for accurate clinical decision-making and assuring research validity.

Confounding adjustment in observational studies on cardiothoracic interventions: a systematic review of methodological practice.

OBJECTIVES: It is unknown which confounding adjustment methods are currently used in the field of cardiothoracic surgery and whether these are appropriately applied. The aim of this study was to systematically evaluate the quality of conduct and reporting of confounding adjustment methods in observational studies on cardiothoracic interventions. METHODS: A systematic review was performed, which included all observational studies that compared different interventions and were published between 1 January and 1 July 2022, in 3 European and American cardiothoracic surgery journals. Detailed information on confounding adjustment methods was extracted and subsequently described. RESULTS: Ninety-two articles were included in the analysis. Outcome regression (n = 49, 53%) and propensity score (PS) matching (n = 44, 48%) were most popular (sometimes used in combination), whereas 11 (12%) studies applied no method at all. The way of selecting confounders was not reported in 42 (46%) of the studies, solely based on previous literature or clinical knowledge in 14 (16%), and (partly) data-driven in 25 (27%). For the studies that applied PS matching, the matched cohorts comprised on average 46% of the entire study population (range 9-82%). CONCLUSIONS: Current reporting of confounding adjustment methods is insufficient in a large part of observational studies on cardiothoracic interventions, which makes quality judgement difficult. Appropriate application of confounding adjustment methods is crucial for causal inference on optimal treatment strategies for clinical practice. Reporting on these methods is an important aspect of this, which can be improved.

Early and late effects of aortic root enlargement: Results from the Pericardial Surgical Aortic Valve Replacement Pivotal Trial: A multicenter, prospective clinical trial.

Objective: During surgical aortic valve replacement, prosthesis-patient mismatch is avoided by implanting the largest possible valve, which sometimes requires annular enlargement (ARE). The effects of ARE on mortality remain controversial. We reviewed data from a multinational clinical trial evaluating a novel pericardial bioprosthesis to determine the influence of ARE 5 years postimplant. Methods: Patients with aortic valve disease requiring surgical aortic valve replacement were prospectively enrolled at 25 centers in North America and 13 centers in Europe. Standardized follow-up was prescribed, including serial echocardiography assessed by a core lab. A composite 30-day end point of major morbidity or mortality was defined as death, reoperation for any cause, stroke, deep sternal wound infection, and acute kidney injury. Results: Among 602 patients with detailed intraoperative data, 90 (15%) underwent ARE with similar rates in North America (17%) and Europe (12%; P = .11). Implanted valve size was similar in both groups (P = .18). The prevalence of moderate or severe prosthesis-patient mismatch at 12 months and at 5 years was comparable between groups, as was the average indexed effective orifice area (P = .3). Five-year survival (ARE, 91% vs no ARE, 89%) and freedom from 30-day major morbidity and mortality (ARE, 87% vs no ARE, 89%) were also similar. Conclusions: In this analysis of a prospective, observational clinical trial, we observed that the performance of an aortic root enlargement procedure did not increase morbidity or mortality at 30 days. We found that survival at 5 years was similar between groups, suggesting that the performance of an ARE procedure restored survival to that observed in patients who did not require an ARE.

Perioperative care differences of surgical aortic valve replacement between North America and Europe.

OBJECTIVE: To describe differences between North America and Europe in the perioperative management of patients undergoing surgical aortic valve replacement (SAVR). METHODS: Patients with moderate or greater aortic stenosis or regurgitation requiring SAVR were enrolled in a prospective observational cohort evaluating the safety and efficacy of a new stented bioprosthesis at 25 centres in North America (Canada and the USA) and 13 centres in Europe (Germany, the Netherlands, France, the UK, Switzerland and Italy). While all patients underwent implantation with the same bioprosthetic model, perioperative management was left to the discretion of participating centres. Perioperative care was described in detail including outcomes up to 1-year follow-up. RESULTS: Among 1118 patients, 643 (58%) were implanted in North America, and 475 (42%) were implanted in Europe. Patients in Europe were older, had a lower body mass index, less bicuspid disease and worse degree of aortic stenosis at baseline. In Europe, anticoagulant therapy at discharge was more aggressive, whereas length of stay was longer, and discharges directly to home were less common. Rehospitalisation risk was lower in Europe at 30 days (8.5% vs 15.9%) but converged at 1-year follow-up (26.5% vs 28.1%). Within continents, there were major differences between individual countries concerning perioperative management. CONCLUSION: Contemporary perioperative management of SAVR patients varies between North America and Europe in patient selection, procedural techniques, antithrombotic regimen and discharge management. Furthermore, rehospitalisation differed largely between continents and countries. Hence, geographical setting must be considered during design and interpretation of trials on SAVR. TRIAL REGISTRATION NUMBER: NCT02088554.

Pledgeted versus nonpledgeted sutures in aortic valve replacement: Insights from a prospective multicenter trial.

Objective: The objective of this study was to compare short- and midterm clinical and echocardiographic outcomes according to the use of pledgeted sutures during aortic valve replacement. Methods: Patients with aortic stenosis or regurgitation requiring aortic valve replacement were enrolled in a prospective cohort study to evaluate the safety of a new stented bioprosthesis. Outcomes were analyzed according to the use of pledgets (pledgeted group) or no pledgets (nonpledgeted group). The primary outcome was a composite of thromboembolism, endocarditis, and major paravalvular leak at 5 years of follow-up. Secondary outcomes included multiple clinical endpoints and hemodynamic outcomes. Propensity score matching was performed to adjust for prognostic factors, and subanalyses with small valve sizes (<23 mm) and suturing techniques were performed. Results: The pledgeted group comprised 640 patients (59%), and the nonpledgeted group 442 (41%), with baseline discrepancies in demographic characteristics, comorbidities, and stenosis severity. There were no differences between groups in any outcome. After propensity score matching, the primary outcome occurred in 41 (11.7%) patients in the pledgeted and 36 (9.8%) in the nonpledgeted group (P = .51). The effective orifice area was smaller in the pledgeted group (P = .045), whereas no difference was observed for the mean or peak pressure gradient. Separate subanalyses with small valve sizes and suturing techniques did not show relevant differences. Conclusions: In this large propensity score-matched cohort, comprehensive clinical outcomes were comparable between patients who underwent aortic valve replacement with pledgeted and nonpledgeted sutures up to 5 years of follow-up, but pledgets might lead to a slightly smaller effective orifice area in the long run.

Minimally Invasive Aortic Valve Replacement in Contemporary Practice: Clinical and Hemodynamic Performance from a Prospective Multicenter Trial.

BACKGROUND: The advent of transcatheter aortic valve replacement (AVR) has led to an increased emphasis on reducing the invasiveness of surgical procedures. The aim of this study was to evaluate clinical outcomes and hemodynamic performance achieved with minimally invasive aortic valve replacement (MI-AVR) as compared with conventional AVR. METHODS: Patients who underwent surgical AVR with the Avalus bioprosthesis, as part of a prospective multicenter non-randomized trial, were included in this analysis. Surgical approach was left to the discretion of the surgeons. Patient characteristics and clinical outcomes were compared between MI-AVR and conventional AVR groups in the entire cohort (n = 1077) and in an isolated AVR subcohort (n = 528). Propensity score adjustment was performed to estimate the effect of MI-AVR on adverse events. RESULTS: Patients treated with MI-AVR were younger, had lower STS scores, and underwent concomitant procedures less often. Valve size implanted was comparable between the groups. MI-AVR was associated with longer procedural times in the isolated AVR subcohort. Postprocedural hemodynamic performance was comparable. There were no significant differences between MI-AVR and conventional AVR in early and 3-year all-cause mortality, thromboembolism, reintervention, or a composite of those endpoints within either the entire cohort or the isolated AVR subcohort. After propensity score adjustment, there remained no association between MI-AVR and the composite endpoint (hazard ratio: 0.86, 95% confidence interval: 0.47-1.55, p = 0.61). CONCLUSION: Three-year outcomes after MI-AVR with the Avalus bioprosthetic valve were comparable to conventional AVR. These results provide important insights into the overall ability to reduce the invasiveness of AVR without compromising outcomes.

The robustness of the flow-gradient classification of severe aortic stenosis.

Objectives: A flow-gradient classification is used to determine the indication for intervention for patients with severe aortic stenosis (AS) with discordant echocardiographic parameters. We investigated the agreement in flow-gradient classification by stroke volume (SV) measurement at the left ventricular outflow tract (LVOT) and at the left ventricle. Methods: Data were used from a prospective cohort study and patients with severe AS (aortic valve area index ≤0.6 cm2/m2) with preserved ejection fraction (>50%) were selected. SV was determined by an echocardiographic core laboratory at the LVOT and by subtracting the 2-dimensional left ventricle end-systolic from the end-diastolic volume (volumetric). Patients were stratified into 4 groups based on SV index (35 mL/m2) and mean gradient (40 mm Hg). The group composition was compared and the agreement between the SV measurements was investigated using regression, correlation, and limits of agreement. In addition, a systematic LVOT diameter overestimation of 1 mm was simulated to study flow-gradient reclassification. Results: Of 1118 patients, 699 were eligible. The group composition changed considerably as agreement on flow state occurred in only 50% of the measurements. LVOT SV was on average 15.1 mL (95% limits of agreement -24.9:55.1 mL) greater than volumetric SV. When a systematic 1-mm LVOT diameter overestimation was introduced, the low-flow groups halved. Conclusions: There was poor agreement in the flow-gradient classification of severe AS as a result of large differences between LVOT and volumetric SV. Furthermore, this classification was sensitive to small measurement errors. These results stress that parameters beyond the flow-gradient classification should be considered to ensure accurate recommendations for intervention.

Why the categorization of indexed effective orifice area is not justified for the classification of prosthesis-patient mismatch.

OBJECTIVES: Although the impact of prosthesis-patient mismatch (PPM) on survival has been widely studied, there has been little debate about whether the current definition of PPM truly reflects hemodynamic obstruction. This study aimed to validate the categorization of indexed effective orifice area (EOAi) for the classification of PPM. METHODS: In total, 2171 patients who underwent aortic valve replacement with a surgical stented bioprosthesis in 5 trials (CoreValve US High-Risk, SURTAVI [Surgical Replacement and Transcatheter Aortic Valve Implantation Trial], Evolut Low Risk, PERIGON [PERIcardial SurGical AOrtic Valve ReplacemeNt] Pivotal Trial for the Avalus valve, and PERIGON Japan) were used for this analysis. The echocardiographic images at the 1-year follow-up visit were evaluated to explore the association between EOAi and mean aortic gradient and its interaction with other patient characteristics, including obesity. In addition, different criteria of PPM were compared with reflect elevated mean aortic gradients (≥20 mm Hg). RESULTS: A relatively smaller exponential decay in mean aortic gradient was found for increasing EOAi, as the slope on the log scale was -0.83 versus -2.5 in the publication from which the current cut-offs for PPM originate. The accuracy of the American Society of Echocardiography, Valve Academic Research Consortium-2, and European Association of Cardiovascular Imaging definitions of PPM to reflect elevated mean aortic gradients was 49%, 57%, and 57%, respectively. The relation between EOAi and mean aortic gradient was not significantly different between obese and non-obese patients (P = .20). CONCLUSIONS: The use of EOAi thresholds to classify patients with PPM is undermined by a less-pronounced exponential relationship between EOAi and mean aortic gradient than previously demonstrated. Moreover, recent adjustment for obesity in the definition of PPM is not supported by these data.

Antithrombotic therapy and bleeding events after aortic valve replacement with a novel bioprosthesis.

OBJECTIVE: Several recent-generation surgical tissue valves have been found to have bleeding rates exceeding rates recommended by regulatory bodies. We explored bleeding events using data from the Pericardial Surgical Aortic Valve Replacement (PERIGON) Pivotal Trial for the Avalus valve (Medtronic, Minneapolis, Minn) to examine whether this end point remains relevant for the evaluation of bioprostheses. METHODS: Patients (n = 1115) underwent aortic valve replacement. Bleeding and thromboembolic event episodes in patients within 3 years postimplant were analyzed for frequency, timing, and severity, focusing on patients taking antiplatelet/anticoagulant medications at the time of the event. Clinical and hemodynamic outcomes are also reported. RESULTS: At 3 years, the Kaplan-Meier cumulative probability estimate of all-cause death was 7.2% (cardiac, 3.6%; valve-related, 1.1%). The Kaplan-Meier cumulative probability estimates of all and major hemorrhage were 8.7% and 5.2%, respectively. Ninety-nine bleeding events occurred in 86 patients: most occurred >30 days postsurgery. Among the 51 late major bleeds, in 5 cases the patients were taking anticoagulant/antiplatelet medication for prophylaxis after surgical aortic valve replacement at the time of the event, whereas the remaining patients were taking medications for other reasons. Age (hazard ratio, 1.035; 95% confidence interval, 1.004-1.068), peripheral vascular disease (hazard ratio, 2.135; 95% confidence interval, 1.106-4.122), renal dysfunction (hazard ratio, 1.920; 95% confidence interval, 1.055-3.494), and antithrombotic medication use at the time of the event (hazard ratio, 1.417; 95% confidence interval, 1.048-1.915) were associated with late bleeds (major and minor). CONCLUSIONS: Overall clinical outcomes demonstrated low mortality and few complications except for major bleeding. Most bleeding events occurred >30 days after surgery and in patients taking antiplatelet and/or anticoagulation for indications other than postimplant prophylaxis.

The fallacy of indexed effective orifice area charts to predict prosthesis-patient mismatch after prosthesis implantation.

AIMS: Indexed effective orifice area (EOAi) charts are used to determine the likelihood of prosthesis-patient mismatch (PPM) after aortic valve replacement (AVR). The aim of this study is to validate whether these EOAi charts, based on echocardiographic normal reference values, can accurately predict PPM. METHODS AND RESULTS: In the PERIcardial SurGical AOrtic Valve ReplacemeNt (PERIGON) Pivotal Trial, 986 patients with aortic valve stenosis/regurgitation underwent AVR with an Avalus valve. Patients were randomly split (50:50) into training and test sets. The mean measured EOAs for each valve size from the training set were used to create an Avalus EOAi chart. This chart was subsequently used to predict PPM in the test set and measures of diagnostic accuracy (sensitivity, specificity, and negative and positive predictive value) were assessed. PPM was defined by an EOAi ≤0.85 cm2/m2, and severe PPM was defined as EOAi ≤0.65 cm2/m2. The reference values obtained from the training set ranged from 1.27 cm2 for size 19 mm up to 1.81 cm2 for size 27 mm. The test set had an incidence of 66% of PPM and 24% of severe PPM. The EOAi chart inaccurately predicted PPM in 30% of patients and severe PPM in 22% of patients. For the prediction of PPM, the sensitivity was 87% and the specificity 37%. For the prediction of severe PPM, the sensitivity was 13% and the specificity 98%. CONCLUSION: The use of echocardiographic normal reference values for EOAi charts to predict PPM is unreliable due to the large proportion of misclassifications.

An in vitro comparison of internally versus externally mounted leaflets in surgical aortic bioprostheses.

OBJECTIVES: To improve haemodynamic performance, design modifications of prosthetic valves have been proposed with each new generation of valves. These different designs also impact the amount of mechanical wear, because mechanical stresses are distributed differently. Because long-term evidence for new prosthetic valves is lacking, this in vitro study compared hydrodynamic performance and durability among 3 currently available bioprosthetic valves with internally (IMLV) or externally mounted leaflets (EMLV). METHODS: Prostheses of the internally mounted Medtronic Avalus and Carpentier-Edwards Perimount Magna Ease valves were compared to prostheses of the externally mounted Abbott Trifecta valve. For each labelled size (e.g. 19, 21 and 23) of the 3 types, 3 valves underwent accelerated wear testing for up to 600 million cycles, corresponding to ∼15 years of simulated wear. The valves underwent hydrodynamic testing and visual inspection. RESULTS: EMLV had the largest effective orifice area and lowest pressure gradient for each labelled size at baseline and 600 million cycles; the effective orifice area and the pressure gradient were equivalent for the 2 types of IMLV. Five of 9 EMLVs had at least 1 hole or tear in the leaflet tissue around the stent posts, which resulted in severe regurgitation at 500 million cycles in 2 cases. All IMLVs were intact at 600 million cycles with minimal tissue wear. CONCLUSIONS: EMLV showed superior hydrodynamic performance but inferior mechanical durability compared to IMLV after 600 million cycles of testing. The primary failures were because of significant mechanical abrasion in the commissural region, which may warrant close monitoring of EMLV during long-term follow-up.