Surgical or Transcatheter Aortic-Valve Replacement in Intermediate-Risk Patients.

BACKGROUND: Although transcatheter aortic-valve replacement (TAVR) is an accepted alternative to surgery in patients with severe aortic stenosis who are at high surgical risk, less is known about comparative outcomes among patients with aortic stenosis who are at intermediate surgical risk. METHODS: We evaluated the clinical outcomes in intermediate-risk patients with severe, symptomatic aortic stenosis in a randomized trial comparing TAVR (performed with the use of a self-expanding prosthesis) with surgical aortic-valve replacement. The primary end point was a composite of death from any cause or disabling stroke at 24 months in patients undergoing attempted aortic-valve replacement. We used Bayesian analytical methods (with a margin of 0.07) to evaluate the noninferiority of TAVR as compared with surgical valve replacement. RESULTS: A total of 1746 patients underwent randomization at 87 centers. Of these patients, 1660 underwent an attempted TAVR or surgical procedure. The mean (±SD) age of the patients was 79.8±6.2 years, and all were at intermediate risk for surgery (Society of Thoracic Surgeons Predicted Risk of Mortality, 4.5±1.6%). At 24 months, the estimated incidence of the primary end point was 12.6% in the TAVR group and 14.0% in the surgery group (95% credible interval [Bayesian analysis] for difference, -5.2 to 2.3%; posterior probability of noninferiority, >0.999). Surgery was associated with higher rates of acute kidney injury, atrial fibrillation, and transfusion requirements, whereas TAVR had higher rates of residual aortic regurgitation and need for pacemaker implantation. TAVR resulted in lower mean gradients and larger aortic-valve areas than surgery. Structural valve deterioration at 24 months did not occur in either group. CONCLUSIONS: TAVR was a noninferior alternative to surgery in patients with severe aortic stenosis at intermediate surgical risk, with a different pattern of adverse events associated with each procedure. (Funded by Medtronic; SURTAVI ClinicalTrials.gov number, NCT01586910 .).

Resuscitation of Endotheliopathy and Bleeding in Thoracic Aortic Dissections: The VIPER-OCTA Randomized Clinical Pilot Trial.

BACKGROUND: Thoracic aorta dissection is an acute critical condition associated with shock-induced endotheliopathy, coagulopathy, massive bleeding, and significant morbidity and mortality. Our aim was to compare the effect of coagulation support with solvent/detergent-treated pooled plasma (OctaplasLG) versus standard fresh frozen plasma (FFP) on glycocalyx and endothelial injury, bleeding, and transfusion requirements. METHODS: Investigator-initiated, single-center, blinded, randomized clinical pilot trial of adult patients undergoing emergency surgery for thoracic aorta dissection. Patients were randomized to receive OctaplasLG or standard FFP as coagulation factor replacement related to bleeding. The primary outcome was glycocalyx and endothelial injury. Other outcomes included bleeding, transfusions and prohemostatics at 24 hours, organ failure, length of stay in the intensive care unit and in the hospital, safety, and mortality at 30 and 90 days. RESULTS: Fifty-seven patients were included to obtain 44 evaluable on the primary outcome. The OctaplasLG group displayed significantly reduced damage to the endothelial glycocalyx (syndecan-1) and reduced endothelial tight junction injury (sVE-cadherin) compared to standard FFP. In the OctaplasLG group compared to the standard FFP, days on ventilator (1 day [interquartile range, 0-1] vs 2 days [1-3]; P = .013), bleeding during surgery (2150 [1600-3087] vs 2750 [2130-6875]; P = .046), 24-hour total transfusion and platelet transfusion volume (3975 mL [2640-6828 mL] vs 6220 mL [4210-10,245 mL]; P = .040, and 1400 mL [1050-2625 mL] vs 2450 mL [1400-3500 mL]; P = .027), and goal-directed use of prohemostatics (7/23 [30.4%] vs 13/21 [61.9%]; P = .036) were all significantly lower. Among the 57 patients randomized, 30-day mortality was 20.7% (6/29) in the OctaplasLG group and 25% (7/28) in the standard FFP group (P = .760). No safety concern was raised. CONCLUSIONS: In this randomized, clinical pilot trial of patients undergoing emergency surgery for thoracic aorta dissections, we found that OctaplasLG reduced glycocalyx and endothelial injury, reduced bleeding, transfusions, use of prohemostatics, and time on ventilator after surgery compared to standard FFP. An adequately powered multicenter trial is warranted to confirm the clinical importance of the findings.

Thrombelastographic hypercoagulability and antiplatelet therapy after coronary artery bypass surgery (TEG-CABG trial): a randomized controlled trial.

A hypercoagulable state has, in observational studies, been associated with increased risk of thromboembolic events. The aim of this trial was to study whether dual antiplatelet therapy (DAPT) with clopidogrel in addition to aspirin could reduce the rate of graft occlusions, thromboembolic events, and death compared to aspirin monotherapy in hypercoagulable patients undergoing coronary artery bypass surgery. A total of 1683 patients were screened for eligibility, among which 165 patients were randomized and 133 patients underwent multislice computed tomography scan to evaluate their grafts. Thrombelastography (TEG) and multiplate aggregometry were performed before and after surgery, and again at three months follow up. TEG hypercoagulability was defined as the maximum amplitude above 69 mm. At three months follow up, 17 out of 66 (25.7%) DAPT patients and 15 of 67 (22.4%) aspirin patients had significant graft stenosis or occlusions (p = 0.839). Saphenous vein grafts (SVGs) were stenosed or occluded in 15 (22.7%) patients in the DAPT group and 7 (10.4%) in the aspirin group (p = 0.167). Thromboembolic events and death after the second postoperative day (when clopidogrel was started) were numerically, but not statistically, lower in the DAPT group, 3 (3.8%) vs. 8 (9.9%), p = 0.211. In univariate logistic regression analysis, only postoperative day 4 platelet response to aspirin measured with multiplate was correlated with graft occlusion, OR 1.020 [1.002-1.039], p = 0.033. This is the first trial to test the hypothesis of intensified antiplatelet therapy in hypercoagulable patients. Due to the low enrollment and high loss to follow up, our results can only be viewed as hypothesis generating. We found a high rate of graft occlusions in this patient population. Our results were not suggestive of that DAPT improved saphenous vein graft patency. A trend was observed in patients on DAPT toward fewer MI and deaths. Postoperative response to aspirin therapy was found to be associated with early SVG occlusion.

Preoperative hemostatic testing and the risk of postoperative bleeding in coronary artery bypass surgery patients.

BACKGROUND: We sought to assess predictability of excessive bleeding using thrombelastography (TEG), multiplate impedance aggregometry, and conventional coagulation tests including fibrinogen in patients undergoing coronary artery bypass graft (CABG) surgery. METHODS: A total of 170 patients were enrolled in this prospective observational study. TEG, Multiplate aggregometry, and coagulation tests were sampled on the day before surgery. Excessive bleeding was defined as >1000 mL over 18 hours. RESULTS: Multiplate-adenosine diphosphate (ADP) measurements were significantly lower in patients with excessive bleeding, 85.5AU ± 32.8 versus 108.5AU ± 30.0, p = 0.012. Bivariate analysis revealed body mass index, myocardial infarction, and multiplate-ADP as predictors of bleeding. In multivariable linear regression analysis, multiplate-ADP remained a significant predictor of bleeding (ß: -6.2 [confidence interval: -12.0 to -0.3], p = 0.035). The lowest interval of multiplate-ADP (<50 AUC) was associated with significantly more bleeding and need for platelet concentrate transfusion. Fibrinogen levels <2.5 g/L were also found to be associated with excess bleeding (p = 0.020). CONCLUSIONS: Multiplate impedance aggregometry identified patients at risk for excessive bleeding after CABG. Low fibrinogen levels were associated with increased bleeding. Neither routine TEG parameters nor conventional coagulation tests were correlated with bleeding.

Temperature effects on incidence of surgery for acute type A aortic dissection in the Nordics.

We aimed to investigate a hypothesised association between daily mean temperature and the risk of surgery for acute type A aortic dissection (ATAAD). For the period of 1 January 2005 until 31 December 2019, we collected daily data on mean temperatures and date of 2995 operations for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Using a two-stage time-series approach, we investigated the association between hot and cold temperatures relative to the optimal temperature and the rate of ATAAD repair in the selected cities. The relative risks (RRs) of cold temperatures (≤-5°C) and hot temperatures (≥21°C) compared to optimal temperature were 1.47 (95% CI: 0.72-2.99) and 1.43 (95% CI: 0.67-3.08), respectively. In line with previous studies, we observed increased risk at cold and hot temperatures. However, the observed associations were not statistically significant, thus only providing weak evidence of an association.

Impact of national holidays and weekends on incidence of acute type A aortic dissection repair.

Previous studies have demonstrated that environmental and temporal factors may affect the incidence of acute type A aortic dissection (ATAAD). Here, we aimed to investigate the hypothesis that national holidays and weekends influence the incidence of surgery for ATAAD. For the period 1st of January 2005 until 31st of December 2019, we investigated a hypothesised effect of (country-specific) national holidays and weekends on the frequency of 2995 surgical repairs for ATAAD at 10 Nordic cities included in the Nordic Consortium for Acute Type A Aortic Dissection (NORCAAD) collaboration. Compared to other days, the number of ATAAD repairs were 29% (RR 0.71; 95% CI 0.54-0.94) lower on national holidays and 26% (RR 0.74; 95% CI 0.68-0.82) lower on weekends. As day of week patterns of symptom duration were assessed and the primary analyses were adjusted for period of year, our findings suggest that the reduced surgical incidence on national holidays and weekends does not seem to correspond to seasonal effects or surgery being delayed and performed on regular working days.

Once after a full moon: acute type A aortic dissection and lunar phases.

OBJECTIVES: Acute type A aortic dissection (ATAAD) is a rare but severe condition, routinely treated with emergent cardiac surgery. Many surgeons have the notion that patients with ATAAD tend to come in clusters, but no studies have examined these observations. This investigation was undertaken to study the potential association between the lunar cycle and the incidence of ATAAD. METHODS: We collected information on 2995 patients who underwent ATAAD surgery at centres from the Nordic Consortium for Acute Type A Aortic Dissection collaboration. We cross-referenced the time of surgery with lunar phase using a case-crossover design with 2 different definitions of full moon (>99% illumination and the 7-day full moon period). RESULTS: The period when the moon was illuminated the most (99% definition) did not show any significant increase in incidence for ATAAD surgery. However, when the full moon period was compared with all other moon phases, it yielded a relative risk of 1.08 [95% confidence interval (CI) 1.00-1.17, P = 0.057] and, compared to waxing moon, only the relative risk was 1.11 (95% CI 1.01-1.23, P = 0.027). The peak incidence came 4-6 days after the moon was fully illuminated. CONCLUSIONS: This study found an overrepresentation of surgery for ATAAD during the full moon phase. The explanation for this is not known, but we speculate that sleep deprivation during full moon leads to a temporary increase in blood pressure, which in turn could trigger rupture of the aortic wall. While this finding is interesting, it needs to be corroborated and the clinical implications are debateable.

Self-expanding Transcatheter vs Surgical Aortic Valve Replacement in Intermediate-Risk Patients: 5-Year Outcomes of the SURTAVI Randomized Clinical Trial.

Importance: In patients with severe aortic valve stenosis at intermediate surgical risk, transcatheter aortic valve replacement (TAVR) with a self-expanding supra-annular valve was noninferior to surgery for all-cause mortality or disabling stroke at 2 years. Comparisons of longer-term clinical and hemodynamic outcomes in these patients are limited. Objective: To report prespecified secondary 5-year outcomes from the Symptomatic Aortic Stenosis in Intermediate Risk Subjects Who Need Aortic Valve Replacement (SURTAVI) randomized clinical trial. Design, Setting, and Participants: SURTAVI is a prospective randomized, unblinded clinical trial. Randomization was stratified by investigational site and need for revascularization determined by the local heart teams. Patients with severe aortic valve stenosis deemed to be at intermediate risk of 30-day surgical mortality were enrolled at 87 centers from June 19, 2012, to June 30, 2016, in Europe and North America. Analysis took place between August and October 2021. Intervention: Patients were randomized to TAVR with a self-expanding, supra-annular transcatheter or a surgical bioprosthesis. Main Outcomes and Measures: The prespecified secondary end points of death or disabling stroke and other adverse events and hemodynamic findings at 5 years. An independent clinical event committee adjudicated all serious adverse events and an independent echocardiographic core laboratory evaluated all echocardiograms at 5 years. Results: A total of 1660 individuals underwent an attempted TAVR (n = 864) or surgical (n = 796) procedure. The mean (SD) age was 79.8 (6.2) years, 724 (43.6%) were female, and the mean (SD) Society of Thoracic Surgery Predicted Risk of Mortality score was 4.5% (1.6%). At 5 years, the rates of death or disabling stroke were similar (TAVR, 31.3% vs surgery, 30.8%; hazard ratio, 1.02 [95% CI, 0.85-1.22]; P = .85). Transprosthetic gradients remained lower (mean [SD], 8.6 [5.5] mm Hg vs 11.2 [6.0] mm Hg; P < .001) and aortic valve areas were higher (mean [SD], 2.2 [0.7] cm2 vs 1.8 [0.6] cm2; P < .001) with TAVR vs surgery. More patients had moderate/severe paravalvular leak with TAVR than surgery (11 [3.0%] vs 2 [0.7%]; risk difference, 2.37% [95% CI, 0.17%- 4.85%]; P = .05). New pacemaker implantation rates were higher for TAVR than surgery at 5 years (289 [39.1%] vs 94 [15.1%]; hazard ratio, 3.30 [95% CI, 2.61-4.17]; log-rank P < .001), as were valve reintervention rates (27 [3.5%] vs 11 [1.9%]; hazard ratio, 2.21 [95% CI, 1.10-4.45]; log-rank P = .02), although between 2 and 5 years only 6 patients who underwent TAVR and 7 who underwent surgery required a reintervention. Conclusions and Relevance: Among intermediate-risk patients with symptomatic severe aortic stenosis, major clinical outcomes at 5 years were similar for TAVR and surgery. TAVR was associated with superior hemodynamic valve performance but also with more paravalvular leak and valve reinterventions.

The challenge of non-adherence to early rehabilitation after coronary artery bypass surgery: Secondary results from the SheppHeartCABG trial.

BACKGROUND: Attending and maintaining a cardiac rehabilitation programme is a challenge. AIMS: The purpose of this study was to explore associations between non-adherence to early coronary artery bypass graft rehabilitation and sociodemographic and clinical baseline data. METHODS: Coronary artery bypass graft patients were randomised 1:1 to either four weeks of comprehensive early rehabilitation or usual care. Outcomes were assessed at three time-points points: baseline, discharge and four weeks post-coronary artery bypass graft. Differences in sociodemographic and clinical baseline data in adherent versus non-adherent patients were tested using the Pearson χ2 test for categorical variables. To test associations between non-adherence to exercise training and sociodemographic and clinical baseline data, multivariate logistic regression was used to estimate the odds ratio for in-hospital training and post-discharge training adjusted for age, sex and left ventricular ejection fraction. RESULTS: Non-adherence to in-hospital versus post-discharge exercise training was 31% (n=48) versus 53% (n=81). Female non-adherence was 20% versus 70%. Non-adherence to in-hospital versus post-discharge mindfulness was 87% versus 70%. Male non-adherence to mindfulness was 85% versus 70%. Non-adherence to psycho-educational consultations was 3%, most of whom were men. Patients with university level education were more adherent to in-hospital exercise training than patients with lower educational level (odds ratio=3.14 (95% confidence interval; 1.16-8.51), p=0.02). Diabetic patients were more non-adherent to exercise training after discharge (3.74 (1.54-9.08), p=0.004) as were overweight patients (0.37 (0.17-0.80), p=0.01). CONCLUSIONS: This study demonstrated wide acceptance of psycho-educational consultations in post-coronary artery bypass graft patients. Adherence to physical rehabilitation was low especially after discharge from hospital and the opportunity to attend a mindfulness programme was not used.

Patients and informal caregivers' experience of surgical and transcatheter aortic valve replacement: Real-world data contributing to establish value-based medicine in Denmark.

BACKGROUND: The concept of value-based medicine (VBM) is increasingly implemented in therapeutic decision-making processes, but only few data on patient-perceived values are available in the field of aortic stenosis treatment. HYPOTHESIS: This study aimed to deliver data on patient-perceived values and health-related quality of life (HR-QoL) following surgical aortic valve replacement (SAVR) and transcatheter aortic valve replacement (TAVR) in a real-world, all-comers patient population. METHODS: Questionnaires were sent to 637 patients who had undergone elective AVR 12 to 24 months earlier in the period September 2015 to August 2016. The questionnaires were specifically designed to assess physical and mental impact of the entire AVR process on patients and their nearest relative and to capture HR-QoL. RESULTS: Questionnaires were completed by 429 patients (SAVR: N = 265; TAVR: N = 164). Both physical and mental impact of the intervention and its recovery period were experienced more stressful by SAVR as compared with TAVR patients. Also, nearest relatives of SAVR patients experienced the entire process mentally more stressful and enduring than relatives of TAVR patients. In both groups, 10% of patients reported no change in HR-QoL, whereas HR-QoL improved in 76% vs 83% (P = 0.092) and worsened in 14% vs 7% (P = 0.040) of the SAVR and TAVR populations, respectively. CONCLUSION: The perioperative experience tends to be more stressful for SAVR as compared with TAVR patients; however, HR-QoL finally improves to a similar degree in both groups. Given the increasing importance of VBM, patient-perceived values will have to be considered in future decision-making processes, both at individual and public policy-making level.

The worldwide mid-term experience with the Medtronic ADVANTAGE bileaflet mechanical heart valve.

BACKGROUND AND AIM OF THE STUDY: A total of 639 patients (479 men, 160 women; mean age 60 +/- 10 years) underwent isolated aortic valve replacement (AVR) between 25 November 1999 and 20 October 2003, using the Medtronic ADVANTAGE bileaflet mechanical heart valve. The study aim was to quantify the clinical performance of a valve with two design modifications: (i) an enlarged central orifice intended to improve blood flow characteristics; and (ii) an asymmetric butterfly pivot recess with expanded outflow component designed to enhance the washing of blood flow through the pivot region. METHODS: Patients were enrolled at 21 centers located in Europe, Canada, Australia, and the USA. The study was conducted under the authority of regional ethics committees, as well as the respective national regulatory agencies. All centers adhered to a common protocol. RESULTS: The total follow up was 1,215.9 patient-years. The average systolic mean pressure gradient across the prosthesis was < 10 mmHg. The mean left ventricular mass index decreased by 22.87 g/m2 (13% reduction) over 12 months. The numbers of valve-related intraoperative, early (< or = 30 days or prior to discharge) and late (> or = 31 days) deaths were 0, 10 and 19, respectively. After one year and four years of follow up, 99.3% (n = 560) and 100% of patients (n = 37), respectively, were in NYHA class I or II. CONCLUSION: The evolutionary bileaflet design of the ADVANTAGE valve achieved the desired clinical functionality and performance.

Choice of Treatment for Aortic Valve Stenosis in the Era of Transcatheter Aortic Valve Replacement in Eastern Denmark (2005 to 2015).

OBJECTIVES: The aim of this study was to evaluate the choice of treatment for severe aortic valve stenosis in the era of transcatheter aortic valve replacement (TAVR) in Eastern Denmark. BACKGROUND: Until the early 21st century, the only therapeutic option for aortic valve stenosis was surgical aortic valve replacement (SAVR), but this has changed with the introduction of TAVR. METHODS: Using the East Denmark Heart Registry, the evolution of AVR over time was studied for the period 2005 to 2015. RESULTS: TAVR has since its introduction in 2007 seen steady growth, with currently more than 35% of AVR procedures-and 45% of isolated AVR procedures-being performed by transcatheter-based technology. The number of SAVR procedures remained rather stable over the study period and even saw a slight decline since 2012-there was a marked decrease in the age at which surgical bioprostheses are considered appropriate. The age profile of TAVR patients remained unchanged over the study period, with a recent trend toward more low- and intermediate-risk patients. Currently, patients age ≥80 years and/or with a Society of Thoracic Surgeons (STS) surgical risk score >6 are automatically referred for TAVR, and one-half of patients age 70 to 80 years with an STS risk score of 4 to 6 are treated with TAVR. CONCLUSIONS: The number of TAVR procedures has increased steadily in recent years, with a TAVR penetration rate of 35% in 2015 and close to 45% when considering isolated AVR. The number of SAVR procedures remained stable over the study period, and surgical bioprostheses are currently used at a much younger age than in 2005.

Patient-prosthesis mismatch and reduction in left ventricular mass after aortic valve replacement.

BACKGROUND: The presence of patient-prosthesis mismatch (PPM) after aortic valve replacement may influence patient survival. We examined the relationship between PPM and changes in left ventricular mass index at 3 months follow-up and also overall survival. METHODS: From patients included in the Mosaic trial, we studied data from 266 patients who underwent aortic valve replacement with the Medtronic Mosaic porcine bioprosthesis and had an echocardiography performed 3 months postoperatively. Complete echocardiographic data, to calculate left ventricular mass index, was available in 78% of the patients. The primary outcome for this substudy was prevalence and severity of PPM. Secondary outcomes were reduction in left ventricular mass index at 3 months follow-up and medium-term survival. Patients without PPM were defined as having an indexed effective orifice area greater than 0.85 cm(2)/m(2), and those with moderate and severe PPM as having an indexed effective orifice area between 0.65 cm(2)/m(2) and 0.85 cm(2)/m(2) or below 0.65 cm(2)/m(2), respectively. RESULTS: PPM was found in 217 (82%) patients. No difference in overall survival was found between patients with PPM and those without PPM. The change in left ventricular mass index was significantly different between groups (no PPM -31.4 ± 28.0 g/m(2), moderate PPM 1.1 ± 34.4 g/m(2), and severe PPM -5.9 ± 29.7 g/m(2), respectively (p = 0.01). CONCLUSIONS: The presence of PPM did not influence medium-term survival. However, patients without PPM showed a marked reduction in left ventricular mass index as soon as 3 months postoperatively.