The joint modeling of longitudinal and time-to-event data is an active area of statistics research that has received a lot of attention in recent years. More recently, a new and attractive ...application of this type of model has been to obtain individualized predictions of survival probabilities and/or of future longitudinal responses. The advantageous feature of these predictions is that they are dynamically updated as extra longitudinal responses are collected for the subjects of interest, providing real time risk assessment using all recorded information. The aim of this article is two-fold. First, to highlight the importance of modeling the association structure between the longitudinal and event time responses that can greatly influence the derived predictions, and second, to illustrate how we can improve the accuracy of the derived predictions by suitably combining joint models with different association structures. The second goal is achieved using Bayesian model averaging, which, in this setting, has the very intriguing feature that the model weights are not fixed but they are rather subject- and time-dependent, implying that at different follow-up times predictions for the same subject may be based on different models. Supplementary materials for this article are available online.
To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical ...research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the US Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included (i) respect for the historical legacy of surgical valve guidelines; (ii) identification of pathophysiological mechanisms associated with clinical events; (iii) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
Congenital heart disease (CHD) accounts for nearly one-third of all major congenital anomalies. CHD birth prevalence worldwide and over time is suggested to vary; however, a complete overview is ...missing. This systematic review included 114 papers, comprising a total study population of 24,091,867 live births with CHD identified in 164,396 individuals. Birth prevalence of total CHD and the 8 most common subtypes were pooled in 5-year time periods since 1930 and in continent and income groups since 1970 using the inverse variance method. Reported total CHD birth prevalence increased substantially over time, from 0.6 per 1,000 live births (95% confidence interval CI: 0.4 to 0.8) in 1930 to 1934 to 9.1 per 1,000 live births (95% CI: 9.0 to 9.2) after 1995. Over the last 15 years, stabilization occurred, corresponding to 1.35 million newborns with CHD every year. Significant geographical differences were found. Asia reported the highest CHD birth prevalence, with 9.3 per 1,000 live births (95% CI: 8.9 to 9.7), with relatively more pulmonary outflow obstructions and fewer left ventricular outflow tract obstructions. Reported total CHD birth prevalence in Europe was significantly higher than in North America (8.2 per 1,000 live births 95% CI: 8.1 to 8.3 vs. 6.9 per 1,000 live births 95% CI: 6.7 to 7.1; p < 0.001). Access to health care is still limited in many parts of the world, as are diagnostic facilities, probably accounting for differences in reported birth prevalence between high- and low-income countries. Observed differences may also be of genetic, environmental, socioeconomical, or ethnic origin, and there needs to be further investigation to tailor the management of this global health problem.
To propose standardized consensus definitions for important clinical endpoints in transcatheter aortic valve implantation (TAVI), investigations in an effort to improve the quality of clinical ...research and to enable meaningful comparisons between clinical trials. To make these consensus definitions accessible to all stakeholders in TAVI clinical research through a peer reviewed publication, on behalf of the public health.
Transcatheter aortic valve implantation may provide a worthwhile less invasive treatment in many patients with severe aortic stenosis and since its introduction to the medical community in 2002, there has been an explosive growth in procedures. The integration of TAVI into daily clinical practice should be guided by academic activities, which requires a harmonized and structured process for data collection, interpretation, and reporting during well-conducted clinical trials.
The Valve Academic Research Consortium established an independent collaboration between Academic Research organizations and specialty societies (cardiology and cardiac surgery) in the USA and Europe. Two meetings, in San Francisco, California (September 2009) and in Amsterdam, the Netherlands (December 2009), including key physician experts, and representatives from the U.S. Food and Drug Administration (FDA) and device manufacturers, were focused on creating consistent endpoint definitions and consensus recommendations for implementation in TAVI clinical research programs. Important considerations in developing endpoint definitions included: 1) respect for the historical legacy of surgical valve guidelines; 2) identification of pathophysiological mechanisms associated with clinical events; 3) emphasis on clinical relevance. Consensus criteria were developed for the following endpoints: mortality, myocardial infarction, stroke, bleeding, acute kidney injury, vascular complications, and prosthetic valve performance. Composite endpoints for TAVI safety and effectiveness were also recommended.
Although consensus criteria will invariably include certain arbitrary features, an organized multidisciplinary process to develop specific definitions for TAVI clinical research should provide consistency across studies that can facilitate the evaluation of this new important catheter-based therapy. The broadly based consensus endpoint definitions described in this document may be useful for regulatory and clinical trial purposes.
Surgical treatment of aortic root aneurysm in Marfan syndrome (MFS) patients.
To compare results of total root replacement versus valve-sparing aortic root replacement in MFS patients.
PubMed, Embase ...and Cochrane library were searched from January 1966 until February 2010 looking for papers reporting on aortic root operations in MFS patients. 530 studies were retrieved.
Finally, 11 publications were enrolled. Inclusion criteria were observational studies reporting valve-related morbidity and mortality after total root replacement (TTR) and/or valve-sparing root replacement (VSRR) in patients with MFS and study size n≥30, reflecting the centre's experience.
Data obtained from papers reporting both TRR and VSRR cohorts were analysed separately. In case of multiple publications, the most recent and complete report was selected. If the total number of patient-years was not provided, we calculated it by multiplying the number of hospital survivors with the mean follow-up duration of that study.
Overall, 1,385 patients were analysed (972 patients had TTR and 413 patients had VSRR). Reintervention rate was 0.3%/year (95% CI 0.1 to 0.5) versus 1.3%/year (95% CI 0.3 to 2.2) (p=0.02) and thromboembolic events rate was 0.7%/year (95% CI 0.5 to 0.9) versus 0.3%/year (95% CI 0.1 to 0.6) (p=0.01) after TRR and VSRR, respectively. When composite valve-related events were compared, no difference existed between the two surgical strategies (p=0.41). Among patients undergoing VSRR, reimplantation was associated with a reduced rate of reintervention compared with remodelling (0.7%/year vs 2.4%/year, p=0.02).
VSRR may represent a valuable option for patients with MFS with aortic aneurysm. However, this technique should be used with caution in patients with valve characteristics at risk for decreased durability.
Objectives Reinterventions after the Ross procedure are a concern for patients and treating physicians. The scope of the present report was to provide an update on the reinterventions observed in the ...large patient population of the German-Dutch Ross Registry. Patients and Methods From 1988 to 2011, 2023 patients (age, 39.05 ± 16.5 years; male patients, 1502; adults, 1642) underwent a Ross procedure in 13 centers. The mean follow-up was 7.1 ± 4.6 years (range, 0-22 years; 13,168 patient-years). Results In the adult population, 120 autograft reinterventions in 113 patients (1.03%/patient-year) and 76 homograft reinterventions in 67 patients (0.65%/patient-year) and, in the pediatric population, 14 autograft reinterventions in 13 patients (0.91%/patient-year) and 42 homograft reinterventions in 31 patients (2.72%/patient-year) were observed. Of the autograft and homograft reinterventions, 17.9% and 21.2% were performed because of endocarditis, respectively. The subcoronary technique in the adult population resulted in significantly superior autograft durability (freedom from autograft reintervention: 97% at 10 years and 91% at 12 years; P < .001). The root replacement technique without root reinforcement (hazard ratio, 2.4; 95% confidence interval, 1.4-4.1) and the presence of pure aortic insufficiency preoperatively (hazard ratio, 2.3; 95% confidence interval, 1.5-3.5) were statistically significant predictors for a shorter time to reoperation. The center volume had a significant influence on the long-term results. The freedom from homograft reoperation for the adults and pediatric population was 97% and 87% at 5 years and 93% and 79% at 12 years, respectively ( P < .001), with younger recipient and donor age being significant predictors of a shorter time to homograft reoperation. Conclusions The autograft principle remains a valid option for young patients requiring aortic valve replacement. The risk of reoperation depends largely on the surgical technique used and the preoperative hemodynamics. Center experience and expertise also influence the long-term results. Adequate endocarditis prophylaxis might further reduce the need for reoperation.
Valve-sparing aortic root techniques have progressively gained ground in the treatment of aortic root aneurysm and aortic insufficiency. By avoiding anticoagulation therapy they offer a good ...alternative to composite graft replacement. This systematic review describes the reported outcome of valve-sparing aortic root replacement, focusing on the remodeling and reimplantation technique. A systematic literature search on the characteristics of and outcomes after valve-sparing aortic root replacement revealed 1,659 articles. The inclusion criteria were a focus on valve-sparing aortic root replacement in adults with aortic root aneurysm, presentation of survival data, and inclusion of at least 30 patients. Data were pooled by inverse variance weighting and analyzed by linear regression. Of 1,659 articles published between January 1, 2000, and January 1, 2014, 31 were included (n = 4,777 patients). The mean age at operation was 51 ± 14.7 years, and 14% of patients had a bicuspid aortic valve. The reimplantation technique was used in 72% and remodeling in 27% (1% other). No clinical advantage in terms of survival and reoperation of one technique over the other was found. Cusp repair was performed in 33%. Pooled early mortality was 2% (n = 103). During follow-up (21,716 patient-years), 262 patients died (survival 92%), and 228 (5%) underwent reoperation, mainly valve replacement. Major adverse valve-related events were low (1.66% patient-years). Preoperative severe aortic valve regurgitation showed a trend toward higher reoperation rate. Remodeling and reimplantation techniques show comparable survival and valve durability results, providing a valid alternative to composite valve replacement. The heterogeneity in the data underlines the need for a collaborative effort to standardize outcome reporting.
The aims of this study were to compare long-term results after homograft versus Freestyle (Medtronic Inc., Minneapolis, Minnesota) aortic root replacement.
The ideal substitute for aortic root ...replacement remains undetermined.
Between 1997 and 2005, 166 patients (age 65 +/- 8 years) undergoing total aortic root replacement were randomized to receive a homograft (n = 76) or a Freestyle bioprosthesis (n = 90). Six patients randomly assigned to homograft crossed over to Freestyle because of unavailability of suitably sized homografts. Median follow-up was 7.6 years (maximum 11 years; 1,035 patient-years). "Evolving" aortic valve dysfunction was defined as aortic regurgitation >/=2/4 and/or peak gradient >20 mm Hg.
Patient characteristics were comparable between groups. Concomitant procedures were performed in 44% and 47% of Freestyle and homograft patients, respectively (p = 0.5). Overall hospital mortality was 4.8% (1% for isolated root replacement). Eight-year survival was 80 +/- 5% in the Freestyle group versus 77 +/- 6% in the homograft group (p = 0.9). Freedom from need for reoperation at 8 years was significantly higher after Freestyle root replacement (100 +/- 0% vs. 90 +/- 5% after homograft replacement; p = 0.02). All reoperations were secondary to structural valve deterioration (n = 6). At last echocardiographic follow-up, actuarial freedom from evolving aortic valve dysfunction was 86 +/- 5% for Freestyle bioprostheses versus 37 +/- 7% for homografts (p < 0.001). Clinically, freedom from New York Heart Association functional class III to IV and freedom from valve-related complications were similar between groups (p = 0.7 and p = 0.9, respectively).
In this patient group, late survival is similar after homograft versus Freestyle root replacement. However, Freestyle aortic root replacement is associated with significantly less progressive aortic valve dysfunction and a lower need for reoperations.
OBJECTIVES
Conventional aortic valve replacement (AVR) in young, active patients represents a suboptimal solution in terms of long-term survival, durability and quality of life. The aim of the ...present work is to present an update on the multicentre experience with the pulmonary autograft procedure in young, adult patients.
METHODS
Between 1990–2013, 1779 adult patients (1339 males; 44.7 ± 11.6 years) underwent the pulmonary autograft procedure in 8 centres. All patients underwent prospective clinical and echocardiographic examinations annually. The mean follow-up was 8.3 ± 5.1 years (range 0–24.3 years) with a total cumulative follow-up of 14 288 years and 662 patients having a follow-up of at least 10 years.
RESULTS
The early (30-day) mortality rate was 1.1% (n = 19). Late (>30 day) survival of the adult population was comparable with the age- and gender-matched general population (observed deaths: 101, expected deaths: 91; P = 0.29). Freedom from autograft reoperation at 5, 10 and 15 years was 96.8, 94.7 and 86.7%, respectively, whereas freedom from homograft reoperation was 97.6, 95.5 and 92.3%, respectively. The overall freedom from reoperation was 94.9, 91.1 and 82.7%, respectively. Longitudinal modelling of functional valve performance revealed a low (<5%) probability of a patient being in higher autograft regurgitation grades throughout the first decade. Similarly, excellent homograft function was observed throughout the first 15 years.
CONCLUSION
The autograft principle results in postoperative long-term survival comparable with that of the age- and gender-matched general population and reoperation rates within the 1%/patient-year boundaries and should be considered in young, active patients who want to avoid the shortcomings of conventional prostheses.
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