Advanced considerations in survival analysis.

Investigation of survival during the follow-up period is common in cardiovascular research and has intrinsic issues that require precise knowledge, such as survival or censoring. Besides, as the follow-up period lengthens and events other than mortality are studied, the analysis becomes more complex, so Kaplan-Meier analyses or Cox models are not always sufficient. In this primer, we provide the reader with detailed information on the interpretation of the most common survival analyses and delve into methods to analyse competing risks or alternatives to the conventional methods when the proportional hazards assumption is not met.

Ultrafast track versus conventional fast track in patients undergoing cardiac surgery: a propensity score-matched analysis.

OBJECTIVES: We aimed at comparing the risk of major adverse events and length of stay between patients undergoing ultrafast track and conventional fast track. METHODS: Retrospective cohort study adjusted by propensity score matching, including patients operated on between March 2020 and December 2022 of any of the following: coronary, valve surgery or ascending aorta surgery. Patients were divided into 2 groups: ultrafast track: extubation in the operating room and fast track: extubation attempted in the first 6 postoperative hours. The primary objective was to compare the risk of the combined event death, lung respiratory outcomes (reintubation, mechanical ventilation longer than 24 h or pneumonia), or acute renal failure. RESULTS: A total of 1126 patients were included. A total of 579 (51.4%) were extubated in the operating room. A total of 331 pairs were available after matching by propensity score. The risk of the primary outcome was 11.8% (n = 39) in the fast-track group and 6.3% (n = 21) in the ultrafast-track group (P = 0.013), mostly driven by lung adverse events (6.9% vs 2.4%, P = 0.011) while no significant differences were detected in the risk of death (2.4% vs 1.8%, P = 0.77) or acute renal failure (8% vs 6.3%, P = 0.56). The risk of myocardial infarction was higher in the fast-track group (2.7% vs 0%, P = 0.039). The median length of stay in the postoperative intensive care unit was longer in the fast-track group [24.7 h (interquartile range 21.5; 62.9) vs 23.5 h (interquartile range 22; 46), P = 0.015]. CONCLUSIONS: In patients undergoing cardiac surgery, extubation in the operating room is associated to a lower risk of postoperative complications (mostly driven by lung adverse events) and length of stay in intensive care unit as compared to fast track.

5-Year haemodynamic performance of three aortic bioprostheses. A randomized clinical trial.

OBJECTIVES: The Carpentier Perimount (CP) Magna Ease, the Crown Phospholipid Reduction Treatment (PRT) and the Trifecta bovine pericardial valves have been widely used worldwide. The primary end point of this study was to compare the haemodynamic performance quantified by in vivo echocardiograms of these 3 aortic prostheses. METHODS: The "BEST-VALVE" (comparison of 3 contemporary cardiac bioprostheses: mid-term valve haemodynamic performance) was a single-centre randomized clinical trial to compare the haemodynamic and clinical outcomes of the aforementioned bioprostheses. The 5-year results are assessed in this manuscript. RESULTS: A total of 154 patients were included. The CP Magna Ease (n = 48, 31.2%), Crown PRT (n = 51, 32.1%) and Trifecta (n = 55, 35.7%) valves were compared. Significant differences were observed among the 3 bioprostheses 5 years after the procedure. The following haemodynamic differences were found between the CP Magna Ease and the Crown PRT bioprostheses [mean aortic gradient: 12.3 mmHg (interquartile range {IQR} 7.8-17.5) for the CP Magna Ease vs 15 mmHg (IQR 10.8-31.9) for the Crown PRT, P < 0.001] and between the CP Magna Ease and the Trifecta prostheses [mean aortic gradient: 12.3 mmHg (IQR 7.8-17.5) for the CP Magna Ease vs 14.7 mmHg (IQR 8.2-55) for the Trifecta, P < 0.001], with a better haemodynamic performance of the CP Magna Ease. The cumulative incidence of severe structural valve degeneration was 9.5% in the Trifecta group at 6 years of follow-up. The 1-, 3- and 5-year survival from all-cause mortality was 91.5%, 83.5% and 74.8%, respectively (log rank P = 0.440). Survival from the composite event at the 1-, 3- and 5-year follow-up was 92.8%, 74.6% and 59%, respectively (log rank P = 0.299). CONCLUSIONS: We detected significant differences between the 3 bioprostheses; the CP Magna Ease had the best haemodynamic performance at the 5-year follow-up.

Neurological outcomes of transcatheter aortic valve implantation with or without cerebral embolic protection devices: A meta-analysis.

INTRODUCTION: Cerebral embolic protection devices (CEPDs) are designed to prevent embolization of debris during transcatheter aortic valve implantation (TAVI). Current evidence from randomized clinical trials (RCTs) and observational studies is controversial. AIMS: The purpose of this meta-analysis was to study the influence of CEPDs on stroke, silent ischemic lesions and neurocognitive function. METHODS: A systematic search was conducted including RCTs or adjusted observational studies comparing TAVI with or without CEPDs. Pooled odds ratios, risk ratios or standardized mean differences with 95% confidence intervals were calculated using the inverse of variance method. Risk of bias sensitivity analyses and meta regression for CEPD type were also conducted. RESULTS: Five RCTs and five adjusted observational studies were included (n= 159,865). Mean age of the patients was 81.1 (SD 1.04) years in CEPDs and 81 (SD 1.86) in non-CEPD. The overall quality of evidence using the GRADE system for each endpoint was low to very low, mainly due to serious risk of bias, inconsistency and imprecision. Random effects meta-analysis detected no significant differences between CEPD and non-CEPD (OR= 0.74; 95% CI 0.51-1.07; P= 0.105; I2= 82.1%) for 30-day stroke. This finding was consistent in meta regression for CEPD type and subgroup analyses by study type and CEPD type. No significant differences between groups were observed in cerebral DW-MRI assessment and neurocognitive function evaluation. CONCLUSION: In the present meta- analysis of five RCTs and five adjusted observational studies, the use of a CEPD during TAVI was not associated with a significant benefit on 30- day stroke, total lesion volume per patient, number of ischemic lesions per patient and neurocognitive function assessments.

Variablity of Mechanical or Tissue Valve Implantation in Patients Undergoing Surgical Aortic Valve Replacement in Spain: National Retrospective Analysis from 2007 to 2018.

BACKGROUND: There is no robust evidence regarding the types of valves implanted among patients undergoing surgical aortic valve replacement (SAVR) in Spain. METHODS: All cases of patients undergoing SAVR ± coronary artery bypass grafting from January 2007 to December 2018 in the public Spanish National Health System were included. We analyzed the trends of SAVR volume, risk profile and type of implanted valve across time and place. Using multivariable logistic regression, we identified factors associated with biological SAVR. RESULTS: In total, 62,870 episodes of SAVR in 15 Spanish territories were included. In 35,693 (56.8%), a tissue valve was implanted. The annual volume of procedures increased from 107.3/million (2007) to 128.6 (2017). In 2018, it fell to 108.5. Age increased and Charlson's comorbity index worsened throughout the study period. Tissue valve implantation increased in most regions. After adjusting for other covariates, we observed a high variability in aortic valve implantation across different regions, with differences of as much as 20-fold in the use of tissue valves. CONCLUSIONS: Between 2007 and 2018, we detected a significant increase in the use of bioprostheses in patients undergoing SAVR in Spain, and a great variability in the types of valve between the Spanish territories, which was not explained by the different risk profiles of patients.

Retrospective cohort analysis of Spanish national trends of coronary artery bypass grafting and percutaneous coronary intervention from 1998 to 2017.

INTRODUCTION: Spain is one of the countries with the lowest rates of revascularisation and highest ratio of percutaneous coronary intervention (PCI) to coronary artery bypass grafting (CABG). OBJECTIVES: To investigate the changes and trends in the two revascularisation procedures between 1998 and 2017 in Spain. DESIGN: Retrospective cohort study. Analysis of in-hospital outcomes. SETTING: Minimum basic data set from the Spanish National Department of Health: mandatory database collecting information of patients who are attended in the Spanish public National Health System. PARTICIPANTS: 603 976 patients who underwent isolated CABG or PCI in the Spanish National Health System. The study period was divided in four 5-year intervals. Patients with acute myocardial infarction on admission were excluded. PRIMARY AND SECONDARY OUTCOMES: We investigated the volume of procedures nationwide, the changes of the risk profile of patients and in-hospital mortality of both techniques. RESULTS: We observed a 2.2-fold increase in the rate of any type of myocardial revascularisation per million inhabitants-year: 357 (1998) to 776 (2017). 93 682 (15.5%) had a coronary surgery. PCI to CABG ratio rose from 2.2 (1998-2002) to 8.1 (2013-2017). Charlson's index increased by 0.8 for CABG and 1 for PCI. The median annual volume of PCI/hospital augmented from 136 to 232, while the volume of CABG was reduced from 137 to 74. In the two decades, we detected a significant reduction of CABG in-hospital mortality (6.5% vs 2.6%, p<0.001) and a small increase in PCI (1.2% vs 1.5%, p<0.001). Risk adjusted mortality rate was reduced for both CABG (1.51 vs 0.48, p<0.001), and PCI (1.42 vs 1.05, p<0.001). CONCLUSION: We detected a significant increase in the volume of revascularisations (particularly PCI) in Spain. Risk-adjusted in-hospital mortality was significantly reduced.

Isolated aortic valve replacement in Spain: national trends in risks, valve types, and mortality from 1998 to 2017.

INTRODUCTION AND OBJECTIVES: To help to illustrate the trends in isolated surgical aortic valve replacement (SAVR) in Spain, we performed a national-level analysis to investigate the changes from 1998 to 2017 in a) SAVR volume, b) patients' risk profiles, c) in-hospital mortality, and d) types of aortic valve prostheses. METHODS: We included all episodes of patients undergoing isolated SAVR from January 1998 to December 2017 recorded in the Minimum Basic Data Set (Ministry of Health, Consumer Affairs, and Social Welfare, Spain). The study duration was divided into four 5-year periods. We analyzed the trends in SAVR volume, comorbidity prevalence, and in-hospital mortality. Through multivariate logistic regression, we identified factors associated with mortality and type of prosthesis. The risk-adjusted mortality rate was compared over the study period. RESULTS: In total, 73 668 patients underwent an isolated SAVR from 1998 to 2017. The annual volume of procedures increased from 16 363 between 1998 and 2002 to 22 685 between 2013 and 2017. The prevalence of all investigated comorbidities increased, except for history of previous myocardial infarction and unplanned admission. The Charlson comorbidity index worsened from 1998-2002 (2.3; SD, 1.4) to 2013-2017 (3.6; SD, 1.7) (P <.001). In-hospital mortality decreased from 7.2% to 3.3% (P <.001) while the risk-adjusted mortality index improved from 1.3 to 0.7. The proportion of bioprostheses increased from 20.7% (1998-2002) to 59.6% (2013-2017) (P <.001). CONCLUSIONS: We detected an increase in the annual SAVR volume in Spain, with more patients receiving bioprostheses. Despite an increased risk profile of the patients, in-hospital mortality substantially reduced.

Combined off-pump mitral repair and thoracoscopic maze surgery.

A 67-year-old man with severe mitral regurgitation and paroxysmal atrial fibrillation was admitted to our institution for surgical repair. The procedure was carried out off-pump. We first performed a totally thoracoscopic maze box lesion set with epicardial transmural radiofrequency, and clipped the left atrial appendage. The mitral valve prolapse was repaired by implanting three transapical neochordae. Six months later, the patient was in sinus rhythm with minimal residual mitral regurgitation on echocardiography. This novel approach is less invasive than the standard surgical correction and should ensure a faster recovery with similar safety and efficacy in selected cases.

Impact of postoperative acute kidney failure in long-term survival after heart valve surgery.

OBJECTIVES: We investigated the impact of acute kidney failure after a heart valve procedure among patients with or without chronic kidney disease (CKD). METHODS: All patients who had undergone a surgical valve procedure between 2005 and 2017 at our institution were divided into 2 groups depending on whether they had previous history of CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2) or not. Homogeneous groups were obtained by propensity score matching. Long-term mortality was compared between the 2 groups and according to the occurrence of postoperative acute kidney failure. Level of significance was set at P-value <0.008 for multiple comparison tests. RESULTS: From the 3907 patients included to this study, 1476 (37.78%) had previous history of CKD. After adjusting for propensity score 1:1, patients with preoperative impaired renal function were at a higher risk of acute kidney failure (26.83% vs 10.16%, P < 0.001) and postoperative mortality (8.48% vs 5.17%, P = 0.001). In the follow-up, they had a poorer survival at 1, 5 and 10 years as compared to patients with normal renal function (88% vs 91.95%, 78.29% vs 81.11% and 56.13% vs 66.29%, respectively; P < 0.001). Patients without postoperative kidney failure had similar survival whether they had preoperative CKD or not [hazard ratio (HR) 1.16, 99.2% confidence interval (CI) 0.87-2.52; P = 0.142]. As compared to patients with postoperative preserved renal function, those with postoperative kidney failure had a higher long-term mortality either if they had previous kidney disease or not [(HR 2.18, 99.2% CI 1.75-2.72; P < 0.001) and (HR 1.48, 99.2% CI 1.33-1.65; P < 0.001), respectively]. Preoperative CKD was the strongest predictor of acute kidney failure (odds ratio 4.45; 95% CI 3.59-5.53; P < 0.001). CONCLUSIONS: Patients with CKD are at higher risk of postoperative adverse events and have poorer long-term outcomes. Postoperative acute kidney failure increases long-term mortality.

Thoracic Stent Grafting through Transapical Approach for Type III Endoleak due to Prosthetic Disconnection.

Thoracic endovascular aortic repair is a well-established treatment of descending thoracic aneurysms, and increasingly complex endovascular procedures including aortic arch and ascending aorta are being performed. However, follow-up complications may be expected, which will enhance the need for alternative approaches such as transapical, in case of complex anatomies and reinterventions. We report the case of a man with prior history of ischemic cardiopathy and multiple endovascular aortic interventions with proximal landing in zone 1 and distal landing proximal to celiac trunk. During the follow-up, the patient developed a 9-cm proximal thoracic aneurysm due to type III endoleak secondary to proximal prosthetic disconnection. Because of severe aortic elongation, inadequate usual vessel accesses (transfemoral/subclavian), and proximity to aortic arch, transapical approach was thought to be the best option in this case. The stent graft was correctly deployed without complications, and the postoperative imaging revealed an excellent result.

Transcatheter versus surgical aortic valve replacement in moderate and high-risk patients: a meta-analysis.

Objectives: The evidence of the benefits of transcatheter aortic valve replacement (TAVR) or surgical aortic valve replacement (SAVR) for patients of high or intermediate surgical risk is not consistent. We performed a meta-analysis to compare major adverse outcomes after TAVR or SAVR. Methods: We searched propensity score matched studies or randomized clinical trials comparing the risks of mortality, stroke, major bleeding, acute renal injury, pacemaker implantation, vascular complications and prostheses haemodynamic performance between TAVR and SAVR in patients with moderate or high risk. Combined odds ratios (ORs), relative risk or mean differences with corresponding 95% confidence intervals (CIs) were calculated using a random effects model. Analyses of sensitivity and publication bias were also conducted. Results: We included 5 clinical trials and 37 observational studies, enrolling 20 224 patients (TAVR, n = 9099 and SAVR, n = 11 125). The pooled analysis suggested no differences in early (OR = 1.11, 95% CI 0.9-1.39, P = 0.355) or late mortality (relative risk = 0.91, 95% CI 0.78-1.05, P = 0.194). TAVR was associated with a lower risk of major bleeding (OR = 0.42, 95% CI 0.25-0.69, P < 0.001) and acute kidney injury (OR = 0.51, 95% CI 0.34-0.71) but with an increase in the incidence of pacemaker implantation (OR = 2.31, 95% CI 1.73-3.08) and vascular complications (OR = 4.88, 95% CI 2.84-8.39). Residual aortic regurgitation was more frequent after TAVR (OR= 6.83, 95% CI 4.87-9.6). SAVR prostheses were associated with poor trans-prosthetic gradients (mean difference: -2.4 mmHg, 95% CI - 3.27 to - 1.53). Conclusions: TAVR and SAVR have similar short and long-term all-cause mortality and risk of stroke among patients of moderate or high surgical risk. TAVR decreases the risk of major bleeding, acute kidney injury and improves haemodynamic performance compared with SAVR but increases the risk of vascular complications, the need for a pacemaker and residual aortic regurgitation.

Validation of EuroSCORE II on a single-centre 3800 patient cohort.

OBJECTIVES: To compare and validate the new European System for Cardiac Operative Risk Evaluation (EuroSCORE) II with EuroSCORE at our institution. METHODS: The logistic EuroSCORE and EuroSCORE II were calculated on the entire patient cohort undergoing major cardiac surgery at our centre between January 2005 and December 2010. The goodness of fit was compared by means of the Hosmer-Lemeshow (HL) chi-squared test and the area under the curve (AUC) of the receiver operating characteristic curves of both scales applied to the same sample of patients. These analyses were repeated and stratified by the type of surgery. RESULTS: Mortality of 5.66% was observed, with estimated mortalities according to logistic EuroSCORE and EuroSCORE II of 9 and 4.46%, respectively. The AUC for EuroSCORE (0.82, 95% confidence interval [CI] 0.79-0.85) was lower than that for EuroSCORE II (0.85, 95% CI 0.83-0.87) without the differences being statistically significant (P = 0.056). Both scales showed a good discriminative capacity for all the pathologies subgroups. The two scales showed poor calibration in the sample: EuroSCORE (χ(2) = 39.3, P(HL) < 0.001) and EuroSCORE II (χ(2) = 86.69, P(HL) < 0.001). The calibration of EuroSCORE was poor in the groups of patients undergoing coronary (P(HL) = 0.01), valve (P(HL) = 0.01) and combined coronary valve surgery (P(HL) = 0.012); and that of EuroSCORE II in the group of coronary (P(HL) = 0.001) and valve surgery (P(HL) < 0.001) patients. CONCLUSIONS: EuroSCORE II demonstrated good discriminative capacity and poor calibration in the patients undergoing major cardiac surgery at our centre.

Mid-term outcomes after off-pump coronary surgery in patients with prior intracoronary stent.

OBJECTIVE: An increasing number of patients undergoing heart surgery have had a prior coronary stent placement. This study was designed to examine the effect of this situation on the mid-term outcomes of off-pump coronary artery bypass graft (OP-CABG) surgery. METHODS: A comparative retrospective non-randomized comparison was performed as follows: all patients undergoing OP-CABG from January 2005 to December 2009 at our centre were divided into two groups: those who did or did not have stents at the time of surgery. We compared the incidences of the following events: (i) death and (ii) combined major adverse cardiac events (MACEs): death, myocardial infarction (MI) and repeat revascularization. Cox's proportional hazards analysis adjusted by a propensity score (n:m) were performed to determine the effects of prior stent placement on the risks of such events. RESULTS: A total of 1020 patients were included, of which 156 (15.6%) had at least one stent. The median follow-up was 32.32 months (interquartile rank 18.08-48). The overall 1, 3 and 5-year survival rates were 95, 92 and 91% for the without-stent group vs. 82, 77 and 74% for the with-stent group, respectively. The 1, 3 and 5-year survival rates free from MACEs were: 92, 87 and 76% for patients without stent vs. 77, 66 and 56% for those with stents. Patients with stent showed an increased risk of death [hazard ratio (HR) 3.631, 95% confidence interval (CI) 2.29-5.756] and MACEs (HR 2.784, 95% CI 1.962-3.951). When adjusted by the propensity score, prior stent placement continued to increase the risks of death (HR 3.795, 95% CI 2.319-6.21) and MACEs (HR 2.89, 95% CI 2.008-4.158). CONCLUSIONS: Patients with intracoronary stents have a lower survival rate and a greater risk of death, MI or need for repeat revascularization during the mid-term follow-up after OP-CABG.

SYNTAX Score is associated with worse outcomes after off-pump coronary artery bypass grafting surgery for three-vessel or left main complex coronary disease.

OBJECTIVE: The SYNergy between percutaneous intervention with TAXus drug eluting stents and cardiac surgery (SYNTAX) Score is a tool for risk stratification of patients according to the complexity of coronary lesions developed during the SYNTAX trial. We examined the influence of the SYNTAX Score on the incidence of major adverse cardiac and cerebrovascular events. METHODS: All patients with de novo left main or 3-vessel disease undergoing coronary artery bypass grafting from January 2005 to December 2008 at our institution (Hospital Clínico San Carlos, Madrid, Spain) were retrospectively assessed, and their SYNTAX Score was calculated. The influence of the SYNTAX Score on postprocedural and follow-up mortality and combined major adverse cardiac and cerebrovascular events (including death, myocardial infarction, cerebrovascular accident, and repeat revascularization) was identified by multivariate analysis. Balancing score analysis was performed to eliminate the effect of potential confounders. RESULTS: A total of 716 patients were enrolled. Mean SYNTAX Score was 34.5 (standard deviation, 6.7; range, 11.5-76). Three groups of patients were identified according to the score terciles: low (≤33), intermediate (33-37), and high (>37). These terciles scores differed greatly from those reported by the SYNTAX trial investigators. The multivariate analysis identified that the SYNTAX Score was associated with follow-up mortality (hazard ratio = 1.046, P = .015) and combined early and follow-up major adverse cardiac and cerebrovascular events (odds ratio = 1.079, P < .001; and hazard ratio = 1.034, P = .026, respectively). Balancing score-adjusted analyses demonstrated that the SYNTAX Score was independently associated with early and late major adverse cardiac and cerebrovascular events (odds ratio = 1.65, P < .001; and hazard ratio = 1.034, P = .027, respectively). CONCLUSIONS: SYNTAX Score was remarkably high among patients undergoing surgical off-pump myocardial revascularization at our institution. In this subset of patients, a higher SYNTAX Score was associated with a higher incidence of in-hospital and follow-up major adverse cardiac and cerebrovascular events after coronary artery bypass grafting, but not with early or late mortality.

Clinical outcomes with off-pump coronary surgery after angioplasty with stent.

INTRODUCTION AND OBJECTIVES: The aim was to determine whether prior coronary stent implantation affects postoperative outcomes in patients undergoing coronary artery bypass grafting. METHODS: Between January 2005 and April 2008, a retrospective analysis was carried out to evaluate the effect of prior coronary stent implantation in patients undergoing off-pump coronary surgery on the incidence of major cardiovascular events in the postoperative period (i.e. at 30 days or during postoperative hospitalization). RESULTS: In total, 796 consecutive patients underwent coronary artery bypass grafting. Of these, 116 (14.6%) had a coronary stent at the time of surgery. Patients with and without stents had similar levels of risk (i.e. EuroSCORE). Multivariate analysis, adjusted for the presence of confounding variables (i.e. preoperative left ventricular ejection fraction <40%, critical preoperative state, age, history of cerebrovascular accident, recent acute myocardial infarction, number of diseased coronary vessels, incomplete revascularization and on-pump conversion), showed that the presence of a stent was significantly associated with increased risks of postoperative myocardial infarction (relative risk [RR]=3.13; 95% confidence interval [CI], 1.75-5.96), in-hospital cardiac mortality (RR=4.62; 95% CI, 1.76-12.11) and in-hospital all-cause mortality (RR=3.65; 95% CI, 1.60-8.34). CONCLUSIONS: In our experience, coronary artery stent implantation prior to coronary surgery was associated with increased risks of postoperative myocardial infarction, cardiac mortality and all-cause mortality in the postoperative period.