Francesco Onorati

Transcatheter aortic valve implantation versus surgical aortic valve replacement for severe aortic stenosis: Results from an intermediate risk propensity-matched population of the Italian OBSERVANT study

BACKGROUND Few studies have yielded information on comparative effectiveness of transcatheter aortic valve implantation (TAVI) versus surgical aortic valve replacement (SAVR) procedures in a real-world setting. The aim of this analysis is to describe procedural and post-procedural outcomes in a TAVI/SAVR intermediate risk propensity-matched population. METHODS OBSERVANT is an observational prospective multicenter cohort study, enrolling AS patients undergoing SAVR or TAVI. Propensity score method was applied to analyze procedural and post-procedural outcomes. Pairs of patients with the same probability score were matched (caliper matching). RESULTS The unadjusted enrolled population (N=2108) comprises 1383 SAVR patients, 602 transarterial-TAVI patients and 123 transapical-TAVI patients. Matched population comprised a total of 266 patients (133 patients for each group). A relatively low risk population was selected (mean logistic EuroSCORE 9.4 ± 10.4% vs 8.9 ± 9.5%, SAVR vs TAVI; p=0.650). Thirty-day mortality was 3.8% for both SAVR and TAVI (p=1.000). The incidence of stroke (1.5% SAVR and 0.0% TAVI; p=0.156) and myocardial infarction (0.8% SAVR and 0.8% TAVI; p=1.000) was not statistically different between groups, whereas a higher requirement for blood transfusion was reported across the surgical cohort (49.6% vs 36.1%; p=0.026). A higher incidence of major vascular damage (5.3% vs. 0.0%; p=0.007) and pacemaker implantation(0.8% vs 12.0%; p=0.001) were reported in the TAVI group. CONCLUSIONS Patients undergoing transcatheter and surgical treatment of severe aortic stenosis are still extremely distinct populations. In the relatively low-risk propensity-matched population analyzed, despite similar procedural and 30-day mortality, SAVR was associated with a higher risk for blood transfusion, whereas TAVI showed a significantly increased rate of vascular damage, permanent AV block and residual aortic valve regurgitation.

A Simple Risk Tool (the OBSERVANT Score) for Prediction of 30-Day Mortality After Transcatheter Aortic Valve Replacement

Risk stratification tools used in patients with severe aortic stenosis have been mostly derived from surgical series. Although specific predictors of early mortality with transcatheter aortic valve replacement (TAVR) have been identified, the prognostic impact of their combination is unexplored. We sought to develop a simple score, using preprocedural variables, for prediction of 30-day mortality after TAVR. A total of 1,878 patients from a national multicenter registry who underwent TAVR were randomly assigned in a 2:1 manner to development and validation data sets. Baseline characteristics of the 1,256 patients in the development data set were considered as candidate univariate predictors of 30-day mortality. A bootstrap multivariate logistic regression process was used to select correlates of 30-day mortality that were subsequently weighted and integrated into a scoring system. Seven variables were weighted proportionally to their respective odds ratios for 30-day mortality (glomerular filtration rate <45 ml/min [6 points], critical preoperative state [5 points], New York Heart Association class IV [4 points], pulmonary hypertension [4 points], diabetes mellitus [4 points], previous balloon aortic valvuloplasty [3 points], and left ventricular ejection fraction <40% [3 points]). The model showed good discrimination in both the development and validation data sets (C statistics 0.73 and 0.71, respectively). Compared with the logistic European System for Cardiac Operative Risk Evaluation in the validation data set, the model showed better discrimination (C statistic 0.71 vs 0.66), goodness of fit (Hosmer-Lemeshow p value 0.81 vs 0.00), and global accuracy (Brier score 0.054 vs 0.073). In conclusion, the risk of 30-day mortality after TAVR may be estimated by combining 7 baseline clinical variables into a simple risk scoring system.

Off-pump coronary artery bypass surgery versus standard linear or pulsatile cardiopulmonary bypass: endothelial activation and inflammatory response

OBJECTIVE Poor outcomes after coronary artery bypass grafting (CABG) have been linked to perioperative endothelial activation and systemic inflammatory responses. The use of pulsatile cardiopulmonary bypass (PCPB) or off-pump CABG (OPCABG) may minimise these phenomena. We compared biochemical and clinical outcomes among patients who underwent CABG with PCPB, CABG with linear CPB (LCPB) or OPCABG. METHODS Sixty consecutive patients undergoing isolated elective CABG were prospectively randomised trial to receive pulsatile CPB (group A, 20 patients), linear CPB (group B, 20 patients) or OPCABG (group C, 20 patients). Levels of proinflammatory cytokines (interleukins-2, -6, and -8), anti-inflammatory cytokines (interleukin-10) and endothelial markers (vascular endothelial growth factor (VEGF), monocyte chemo-attractant protein (MCP)-1) were measured before, during and after surgery. RESULTS VEGF and MCP-1 levels increased significantly during surgery in all groups, but they increased the least and were the lowest overall with OPCABG. They rose most and peaked overall with LCPB. Interleukin-2 levels remained stable during OPCABG but decreased equally during PCPB and LCPB. Interleukin-6 and -8 levels rose significantly during both types of CPB versus OPCABG. Interleukin-10 levels increased significantly in all groups during surgery, but they rose least and were the lowest overall with OPCABG and rose most and were the highest overall with PCPB. Intubation times, intensive care unit (ICU) stay and hospital stay were significantly longer in the LCPB group than the other two groups. CONCLUSIONS LCPB appears to promote endothelial activation and cytokine secretion, which may delay recovery. OPCABG was associated with slight endothelial activation and cytokine response. PCPB significantly attenuates endothelial/cytokine leakage, resulting in hospital outcomes comparable with those after OPCABG.

Immediate and Intermediate Outcome After Transapical Versus Transfemoral Transcatheter Aortic Valve Replacement

A few studies recently reported controversial results with transfemoral transcatheter aortic valve replacement (TF-TAVR) versus transapical transcatheter aortic valve replacement (TA-TAVR), often without adequate adjusted analysis for baseline differences. Data on patients who underwent TF-TAVR and TA-TAVR from the Observational Study of Effectiveness of avR-tavI procedures for severe Aortic stenosis Treatment study were analyzed with propensity score 1-to-1 matching. From a cohort of 1,654 patients (1,419 patients underwent TF-TAVR and 235 patients underwent TA-TAVR), propensity score matching resulted in 199 pairs of patients with similar operative risk (EuroSCORE II: TF-TAVR 8.1 ± 7.1% vs TA-TAVR, 8.4 ± 7.3%, p = 0.713). Thirty-day mortality was 8.0% after TA-TAVR and 4.0% after TF-TAVR (p = 0.102). Postoperative rates of stroke (TA-TAVR, 2.0% vs TF-TAVR 1.0%, p = 0.414), cardiac tamponade (TA-TAVR, 4.1% vs TF-TAVR 1.5%, p = 0.131), permanent pacemaker implantation (TA-TAVR, 8.7% vs TF-TAVR 13.3%, p = 0.414), and infection (TA-TAVR, 6.7% vs TF-TAVR 3.6%, p = 0.180) were similar in the study groups but with an overall trend in favor of TF-TAVR. Higher rates of major vascular damage (7.2% vs 1.0%, p = 0.003) and moderate-to-severe paravalvular regurgitation (7.8% vs 5.2%, p = 0.008) were observed after TF-TAVR. On the contrary, TA-TAVR was associated with higher rates of red blood cell transfusion (50.0% vs 30.4%, p = 0.0002) and acute kidney injury (stages 1 to 3: 44.4% vs 21.9%, p <0.0001) compared with TF-TAVR. Three-year survival rate was 69.1% after TF-TAVR and 57.0% after TA-TAVR (p = 0.006), whereas freedom from major adverse cardiovascular and cerebrovascular events was 61.9% after TF-TAVR and 50.4% after TA-TAVR (p = 0.011). In conclusion, TF-TAVR seems to be associated with significantly higher early and intermediate survival compared with TA-TAVR. The transfemoral approach, whenever feasible, should be considered the route of choice for TAVR.

Preoperative Statin Therapy Is Not Associated With a Decrease in the Incidence of Delirium After Cardiac Operations

BACKGROUND Delirium after cardiac operations is associated with significant morbidity and death. Statins have been recently suggested to exert protective cerebral effects. This study investigated whether preoperative statins were associated with decreased incidence of postoperative delirium in patients undergoing coronary artery bypass grafting. METHODS The study enrolled 4,659 consecutive patients (21% women; age, 67.8±9.2 years) undergoing coronary artery bypass grafting. A propensity score-based optimal-matching algorithm was used to match 1,577 patients receiving preoperative statins with a control group (1:1). Patients were screened for delirium in the intensive care unit according to the Confusion Assessment Method for the intensive care unit. RESULTS Delirium affected 89 patients (3%), and preoperative statin administration was not multivariably associated with a decreased incidence of delirium (odds ratio, 1.52; 95% confidence interval, 0.97 to 2.37; p=0.18) and was also unrelated to a delirium decrease in patient subgroups undergoing isolated coronary artery bypass grafting (odds ratio, 1.31; 95% confidence interval, 0.68 to 2.52; p=0.51) or combined valvular procedures (odds ratio, 1.72; 95% confidence interval, 0.96 to 3.07, p=0.08). Similar results were observed for age groups and cardiopulmonary bypass durations. Patients affected by postoperative delirium experienced a longer hospital stay (25th to 75th percentile) of 11 (7 to 18 days) vs 7 days (7 to 8 days, p<0.001) and 12% hospital mortality vs 1% (p<0.001). CONCLUSIONS Preoperative statins were not associated with a decreased incidence of delirium in patients undergoing coronary revascularization.

Impact of clonidine administration on delirium and related respiratory weaning after surgical correction of acute type-A aortic dissection: results of a pilot study

Delirium and transient neurologic dysfunctions (TND) often complicate the postoperative course after surgery for acute type-A aortic dissection (AAD). We evaluated the role of clonidine on neurological outcome and respiratory function in 30 consecutive patients undergoing surgery for AAD. Patients were prospectively randomized to receive either clonidine (0.5 microg/kg bolus, followed by continuous infusion at 1-2 microg/kg/h) or placebo (NaCl 0.9%) in on starting and throughout the weaning period from the mechanical ventilation. Incidence of delirium and TND, Delirium Detection Score (DDS), weaning parameters [respiratory rate to tidal volume ratio - f/VT; pressure-frequency product (PFP); partial pressure of arterial oxygen to fractional inspired oxygen concentration (PaO(2)/FiO(2)); partial pressure of carbon dioxide (PaCO(2))], weaning duration and intensive care unit (ICU) length of stay were recorded. The two groups were similar for preoperative and operative variables and also for the incidence of postoperative complications. DDS was lower in the clonidine group (P<0.001). Patients weaned with clonidine showed lower f/VT and PFP, higher PaO(2)/FiO(2) and PaCO(2), lower DDS, weaning period and the related ICU length of stay (P<0.001). This was further confirmed in patients developing delirium/TND. Intravenous clonidine after surgery for AAD reduces the severity of delirium, improves the respiratory function, shortens the weaning duration and the ICU length of stay.

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: A prospective randomized study on the timing of perioperative intraaortic balloon pump support

In this prospective trial the results of preoperative and intraoperative IABP in coronary artery bypass graft (CABG) patients with low left ventricular ejection fraction (LVEF) were compared. Sixty CABG patients with preoperative LVEF ≤0.30 were enrolled: in group A patients (n=30) IABP was started within 2 hours preoperatively; in group B (n=30) it was instituted intraoperatively before weaning from cardiopulmonary bypass. Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography. Hospital survival, length of IABP support, intubation, ICU and hospital stay, need for postoperative inotropic drugs and incidence of myocardial infarction were compared between the two groups. Survival in group A patients proved significantly higher (P=0.047). Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients (p<0.001). Doses of inotropic drugs (dobutamine, enoximone) were lower in group A (P=0.001; P=0.004) and duration shorter (p<0.001; p<0.001). No major IABP-related complication was observed.

Routine ganglionic plexi ablation during Maze procedure improves hospital and early follow-up results of mitral surgery

OBJECTIVE Ganglionic plexi are claimed to be potentially responsible for atrial fibrillation. We evaluated whether ganglionic plexi isolation improves the results of the Maze procedure during mitral valve surgery. METHODS A total of 75 patients with atrial fibrillation underwent radiofrequency ablation during mitral valve surgery without (group A) or with (group B) ganglionic plexi ablation with bipolar radiofrequency plus fat pad resection along the Waterston groove, left pulmonary veins, and Marshalls ligament. Ganglionic plexi were intraoperatively mapped, and fat pad specimens were sectioned and analyzed. Hospital and follow-up results were recorded. Amiodarone was discontinued at the sixth month. RESULTS Active ganglionic plexi were mainly located in the upper parts of fat pads. Active specimens demonstrated more ganglionic plexi than inactive specimens (P <or= .015 at different levels) but did not correlate with atrial fibrillation recurrence (P = not significant). Atrial fibrillation was higher in group A at aortic declamping (P = .03) and discharge (P = .03). Early events were comparable (P = .565). At 16.7 +/- 0.95 (standard error) months, the cumulative freedom from atrial fibrillation, atrial flutter, and atrial tachycardia with antiarrhythmic therapy was 63.2% +/- 7.3% and proved higher in group B (83.9% +/- 7.9% vs group A 52.8% +/- 8.7%; P = .035). However, after the sixth month, at 12.8 +/- 0.80 months, freedom from atrial fibrillation, atrial flutter, and atrial tachycardia without antiarrhythmic therapy was 72.5% +/- 7.7% and proved higher in group B (92.9% +/- 6.9% vs 62.5% +/- 9.4%; P = .023). A higher proportion of patients in group B showed normalized E/A ratio (61.3% vs group A 36.4%; P = .029). No differences were detected in follow-up freedom from congestive heart failure (group A: 83.4% +/- 7.0% vs group B: 93.5% +/- 4.4%; P = .978) and hospital readmission (group A: 84.2% +/- 5.9% vs group B: 92.6% +/- 5.1%; P = .376). CONCLUSION Ganglionic plexi isolation can improve hospital and follow-up results during mitral valve surgery and possibly ameliorate echocardiographic recovery of atrial function during follow-up.

Transcatheter Aortic Valve Implantation Compared With Surgical Aortic Valve Replacement in Low-Risk Patients

Background—The proven efficacy of transcatheter aortic valve implantation (TAVI) in high-risk patients is leading to the expansion of its indications toward lower-risk patients. However, this shift is not supported by meaningful evidence of its benefit over surgical aortic valve replacement (SAVR). This analysis aims to describe outcomes of TAVI versus SAVR in low-risk patients. Methods and Results—We compared the outcome after TAVI and SAVR of low-risk patients (European System for Cardiac Operative Risk Evaluation II [EuroSCORE II] <4%) included in the Observational Study of Effectiveness of SAVR–TAVI Procedures for Severe Aortic Stenosis Treatment (OBSERVANT) study. The primary outcome was 3-year survival. Secondary outcomes were early events and major adverse cardiac and cerebrovascular events at 3 years. Propensity score matching resulted in 355 pairs of patients with similar baseline characteristics. Thirty-day survival was 97.1% after SAVR and 97.4% after TAVI (P=0.82). Cardiac tamponade, permanent pacemaker implantation, major vascular damage, and moderate-to-severe paravalvular regurgitation were significantly more frequent after TAVI compared with SAVR. Stroke rates were equal in the study groups. SAVR was associated with higher risk of cardiogenic shock, severe bleeding, and acute kidney injury. At 3 years, survival was 83.4% after SAVR and 72.0% after TAVI (P=0.0015), whereas freedom from major adverse cardiac and cerebrovascular events was 80.9% after SAVR and 67.3% after TAVI (P<0.001). Conclusions—In patients with low operative risk, significantly better 3-year survival and freedom from major adverse cardiac and cerebrovascular events were observed after SAVR compared with TAVI. Further studies on new-generation valve prostheses are necessary before expanding indications of TAVI toward lower-risk patients.

European Multicenter Study on Coronary Artery Bypass Grafting (E-CABG registry): Study Protocol for a Prospective Clinical Registry and Proposal of Classification of Postoperative Complications

BackgroundClinical evidence in coronary surgery is usually derived from retrospective, single institutional series. This may introduce significant biases in the analysis of critical issues in the treatment of these patients. In order to avoid such methodological limitations, we planned a European multicenter, prospective study on coronary artery bypass grafting, the E-CABG registry.DesignThe E-CABG registry is a multicenter study and its data are prospectively collected from 13 centers of cardiac surgery in university and community hospitals located in six European countries (England, Italy, Finland, France, Germany, Sweden). Data on major and minor immediate postoperative adverse events will be collected. Data on late all-cause mortality, stroke, myocardial infarction and repeat revascularization will be collected during a 10-year follow-up period. These investigators provided a score from 0 to 10 for any major postoperative adverse events and their rounded medians were used to stratify the severity of these complications in four grades. The sum of these scores for each complication/intervention occurring after coronary artery bypass grafting will be used as an additive score for further stratification of the prognostic importance of these events.DiscussionThe E-CABG registry is expected to provide valuable data for identification of risk factors and treatment strategies associated with suboptimal outcome. These information may improve the safety and durability of coronary artery bypass grafting. The proposed classification of postoperative complications may become a valuable research tool to stratify the impact of such complications on the outcome of these patients and evaluate the burden of resources needed for their treatment.Clinical Trials numberNCT02319083