How microsimulation translates outcome estimates to patient lifetime event occurrence in the setting of heart valve disease.

Treatment decisions in healthcare often carry lifelong consequences that can be challenging to foresee. As such, tools that visualize and estimate outcome after different lifetime treatment strategies are lacking and urgently needed to support clinical decision-making in the setting of rapidly evolving healthcare systems, with increasingly numerous potential treatments. In this regard, microsimulation models may prove to be valuable additions to current risk-prediction models. Notable advantages of microsimulation encompass input from multiple data sources, the ability to move beyond time-to-first-event analysis, accounting for multiple types of events and generating projections of lifelong outcomes. This review aims to clarify the concept of microsimulation, also known as individualized state-transition models, and help clinicians better understand its potential in clinical decision-making. A practical example of a patient with heart valve disease is used to illustrate key components of microsimulation models, such as health states, transition probabilities, input parameters (e.g. evidence-based risks of events) and various aspects of mortality. Finally, this review focuses on future efforts needed in microsimulation to allow for increasing patient-tailoring of the models by extending the general structure with patient-specific prediction models and translating them to meaningful, user-friendly tools that may be used by both clinician and patient to support clinical decision-making.

Aortic valve repair in neonates, infants and children: a systematic review, meta-analysis and microsimulation study.

OBJECTIVES: To support clinical decision-making in children with aortic valve disease, by compiling the available evidence on outcome after paediatric aortic valve repair (AVr). METHODS: A systematic review of literature reporting clinical outcome after paediatric AVr (mean age at surgery <18 years) published between 1 January 1990 and 23 December 2021 was conducted. Early event risks, late event rates and time-to-event data were pooled. A microsimulation model was employed to simulate the lives of individual children, infants and neonates following AVr. RESULTS: Forty-one publications were included, encompassing 2 623 patients with 17 217 patient-years of follow-up (median follow-up: 7.3 years; range: 1.0-14.4 years). Pooled mean age during repair for aortic stenosis in children (<18 years), infants (<1 year) or neonates (<30 days) was 5.2 ± 3.9 years, 35 ± 137 days and 11 ± 6 days, respectively. Pooled early mortality after stenosis repair in children, infants and neonates, respectively, was 3.5% (95% confidence interval: 1.9-6.5%), 7.4% (4.2-13.0%) and 10.7% (6.8-16.9%). Pooled late reintervention rate after stenosis repair in children, infants and neonates, respectively, was 3.31%/year (1.66-6.63%/year), 6.84%/year (3.95-11.83%/year) and 6.32%/year (3.04-13.15%/year); endocarditis 0.07%/year (0.03-0.21%/year), 0.23%/year (0.07-0.71%/year) and 0.49%/year (0.18-1.29%/year); and valve thrombosis 0.05%/year (0.01-0.26%/year), 0.15%/year (0.04-0.53%/year) and 0.19%/year (0.05-0.77%/year). Microsimulation-based mean life expectancy in the first 20 years for children, infants and neonates with aortic stenosis, respectively, was 18.4 years (95% credible interval: 18.1-18.7 years; relative survival compared to the matched general population: 92.2%), 16.8 years (16.5-17.0 years; relative survival: 84.2%) and 15.9 years (14.8-17.0 years; relative survival: 80.1%). Microsimulation-based 20-year risk of reintervention in children, infants and neonates, respectively, was 75.2% (72.9-77.2%), 53.8% (51.9-55.7%) and 50.8% (47.0-57.6%). CONCLUSIONS: Long-term outcomes after paediatric AVr for stenosis are satisfactory and dependent on age at surgery. Despite a high hazard of reintervention for valve dysfunction and slightly impaired survival relative to the general population, AVr is associated with low valve-related event occurrences and should be considered in children with aortic valve disease.

Paediatric aortic valve replacement: a meta-analysis and microsimulation study.

AIMS: To support decision-making in children undergoing aortic valve replacement (AVR), by providing a comprehensive overview of published outcomes after paediatric AVR, and microsimulation-based age-specific estimates of outcome with different valve substitutes. METHODS AND RESULTS: A systematic review of published literature reporting clinical outcome after paediatric AVR (mean age <18 years) published between 1/1/1990 and 11/08/2021 was conducted. Publications reporting outcome after paediatric Ross procedure, mechanical AVR (mAVR), homograft AVR (hAVR), and/or bioprosthetic AVR were considered for inclusion. Early risks (<30d), late event rates (>30d) and time-to-event data were pooled and entered into a microsimulation model. Sixty-eight studies, of which one prospective and 67 retrospective cohort studies, were included, encompassing a total of 5259 patients (37 435 patient-years; median follow-up: 5.9 years; range 1-21 years). Pooled mean age for the Ross procedure, mAVR, and hAVR was 9.2 ± 5.6, 13.0 ± 3.4, and 8.4 ± 5.4 years, respectively. Pooled early mortality for the Ross procedure, mAVR, and hAVR was 3.7% (95% CI, 3.0%-4.7%), 7.0% (5.1%-9.6%), and 10.6% (6.6%-17.0%), respectively, and late mortality rate was 0.5%/year (0.4%-0.7%/year), 1.0%/year (0.6%-1.5%/year), and 1.4%/year (0.8%-2.5%/year), respectively. Microsimulation-based mean life-expectancy in the first 20 years was 18.9 years (18.6-19.1 years) after Ross (relative life-expectancy: 94.8%) and 17.0 years (16.5-17.6 years) after mAVR (relative life-expectancy: 86.3%). Microsimulation-based 20-year risk of aortic valve reintervention was 42.0% (95% CI: 39.6%-44.6%) after Ross and 17.8% (95% CI: 17.0%-19.4%) after mAVR. CONCLUSION: Results of paediatric AVR are currently suboptimal with substantial mortality especially in the very young with considerable reintervention hazards for all valve substitutes, but the Ross procedure provides a survival benefit over mAVR. Pros and cons of substitutes should be carefully weighed during paediatric valve selection.

Outcomes after right ventricular outflow tract reconstruction with valve substitutes: A systematic review and meta-analysis.

Introduction: This study aims to provide an overview of outcomes after right ventricular outflow tract (RVOT) reconstruction using different valve substitutes in different age groups for different indications. Methods: The literature was systematically searched for articles published between January 2000 and June 2021 reporting on clinical and/or echocardiographic outcomes after RVOT reconstruction with valve substitutes. A random-effects meta-analysis was conducted for outcomes, and time-related outcomes were visualized by pooled Kaplan-Meier curves. Subgroup analyses were performed according to etiology, implanted valve substitute and patient age. Results: Two hundred and seventeen articles were included, comprising 37,078 patients (age: 22.86 ± 11.29 years; 31.6% female) and 240,581 patient-years of follow-up. Aortic valve disease (Ross procedure, 46.6%) and Tetralogy of Fallot (TOF, 27.0%) were the two main underlying etiologies. Homograft and xenograft accounted for 83.7 and 32.6% of the overall valve substitutes, respectively. The early mortality, late mortality, reintervention and endocarditis rates were 3.36% (2.91-3.88), 0.72%/y (95% CI: 0.62-0.82), 2.62%/y (95% CI: 2.28-3.00), and 0.38%/y (95%CI: 0.31-0.47) for all patients. The early mortality for TOF and truncus arteriosus (TA) were 1.95% (1.31-2.90) and 10.67% (7.79-14.61). Pooled late mortality and reintervention rate were 0.59%/y (0.39-0.89), 1.41%/y (0.87-2.27), and 1.20%/y (0.74-1.94), 10.15%/y (7.42-13.90) for TOF and TA, respectively. Endocarditis rate was 0.21%/y (95% CI: 0.16-0.27) for a homograft substitute and 0.80%/y (95%CI: 0.60-1.09) for a xenograft substitute. Reintervention rate for infants, children and adults was 8.80%/y (95% CI: 6.49-11.95), 4.75%/y (95% CI: 3.67-6.14), and 0.72%/y (95% CI: 0.36-1.42), respectively. Conclusion: This study shows RVOT reconstruction with valve substitutes can be performed with acceptable mortality and morbidity rates for most patients. Reinterventions after RVOT reconstruction with valve substitutes are inevitable for most patients in their life-time, emphasizing the necessity of life-long follow-up and multidisciplinary care. Follow-up protocols should be tailored to individual patients because patients with different etiologies, ages, and implanted valve substitutes have different rates of mortality and morbidity. Systematic review registration: [www.crd.york.ac.uk/prospero], identifier [CRD42021271622].

Meta-Analysis of Bilateral Versus Single Internal Thoracic Artery Grafting in Patients ≥70 Years of Age.

The optimal choice of graft material in patients ≥70 years of age undergoing coronary artery bypass grafting remains unknown. A systematic review of literature was conducted by searching PubMed, Embase, Web of Science, and Cochrane Library databases for original publications that compared bilateral internal thoracic artery (BITA) grafting with single internal thoracic artery grafting in patients ≥70 years of age. Data were extracted by 2 independent investigators and meta-analyzed with the use of random effects. A total of 10 studies, including 11,185 patients, met the inclusion criteria. No differences in early mortality and morbidity, with the exemption of sternal wound complications which were more frequently observed in the BITA group (odds ratio 1.72, 95% 1.00 to 2.96 confidence interval [CI], p = 0.05; propensity score-matched population odds ratio 1.58, 95% CI 1.09 to 2.29, p = 0.02), were observed. Overall survival was superior in the overall patient population (hazard ratio [HR] 0.76, 95% CI 0.66 to 0.86, p <0.001), after applying a blanking period of 3 months to the overall patient population (HR 0.77, 95% CI 0.64 to 0.92, p = 0.005) as well as in the matched population (HR 0.72, 95% CI 0.58 to 0.89, p = 0.002); in all cases, a benefit was readily seen within a few years after surgery. The difference in freedom from major adverse cardiac and cerebrovascular events failed to reach statistical significance (overall patient population HR 0.55, 95% CI 0.27 to 1.13, p = 0.10; matched population HR 0.52, 95% CI 0.23 to 1.16, p = 0.11). In conclusion, BITA grafting can be safely performed in patients ≥70 years of age as late clinical benefits are expected to manifest themselves readily within a few years after surgery.

Reconstruction of the Aortic Arch in Neonates and Infants: The Importance of Patch Material.

OBJECTIVES: Restenosis after aortic arch reconstruction is a known complication in neonates and infants. Homograft is the most commonly used patch material for aortic arch reconstructions in our center. Since 2014, tissue-engineered bovine pericardium (CardioCel) has been used as an alternative. The aim of our study was to determine whether the choice of material affected the development of restenosis in these patients. METHODS: Data of all neonates and infants who underwent aortic arch reconstruction with the use of any patch material between 2005 and 2016 were analyzed. Restenosis was defined by the need for reintervention, either percutaneous or surgical. RESULTS: Forty-one patients underwent aortic arch repair. Excluding the 30-day mortality, 36 patients represented the study population. At primary repair, the aortic arch was reconstructed with homograft (n = 26) or CardioCel (n = 10). Restenosis was documented during the first year of life in 13 patients: Six (23%) patients in the homograft group and seven (70%) patients in the CardioCel group (P = .01). In the homograft group, the median time from operation to first intervention for restenosis was 22.0 (range: 14-32) weeks, as compared to 14.0 (range: 7-21) weeks in the CardioCel group (P = .04). CONCLUSION: We conclude that choice of patch material is likely to be an important determinant for the risk of restenosis needing reintervention following reconstruction of the aortic arch in neonates and infants.

Patient information portal for congenital aortic and pulmonary valve disease: a stepped-wedge cluster randomised trial.

BACKGROUND: In response to an increased need for patient information in congenital heart disease, we previously developed an online, evidence-based information portal for patients with congenital aortic and pulmonary valve disease. To assess its effectiveness, a stepped-wedge cluster randomised trial was conducted. METHODS: Adult patients and caregivers of paediatric patients with congenital aortic and/or pulmonary valve disease and/or tetralogy of Fallot who visited the outpatient clinic at any of the four participating centres in the Netherlands between 1 March 2016-1 July 2017 were prospectively included. The intervention (information portal) was introduced in the outpatient clinic according to a stepped-wedge randomised design. One month after outpatient clinic visit, each participant completed a questionnaire on disease-specific knowledge, anxiety, depression, mental quality of life, involvement and opinion/attitude concerning patient information and involvement. RESULTS: 343 participants were included (221 control, 122 intervention). Cardiac diagnosis (p=0.873), educational level (p=0.153) and sex (p=0.603) were comparable between the two groups. All outcomes were comparable between groups in the intention-to-treat analyses. However, only 51.6% of subjects in the intervention group (n=63) reported actually visiting the portal. Among these subjects (as-treated), disease-specific knowledge (p=0.041) and mental health (p=0.039) were significantly better than in control subjects, while other baseline and outcome variables were comparable. CONCLUSION: Even after being invited by their cardiologists, only half of the participants actually visited the information portal. Only in those participants that actually visited the portal, knowledge of disease and mental health were significantly better. This underlines the importance of effective implementation of online evidence-based patient information portals in clinical practice.

Prosthesis-patient mismatch after mitral valve replacement: A pooled meta-analysis of Kaplan-Meier-derived individual patient data.

OBJECTIVE: The hemodynamic effect and early and late survival impact of prosthesis-patient mismatch (PPM) after mitral valve replacement remains insufficiently explored. METHODS: Pubmed, Embase, Web of Science, and Cochrane Library databases were searched for English language original publications. The search yielded 791 potentially relevant studies. The final review and analysis included 19 studies compromising 11,675 patients. RESULTS: Prosthetic effective orifice area was calculated with the continuity equation method in 7 (37%), pressure half-time method in 2 (10%), and partially or fully obtained from referenced values in 10 (53%) studies. Risk factors for PPM included gender (male), diabetes mellitus, chronic renal disease, and the use of bioprostheses. When pooling unadjusted data, PPM was associated with higher perioperative (odds ratio [OR]: 1.66; 95% confidence interval [CI]: 1.32-2.10; p < .001) and late mortality (hazard ratio [HR]: 1.46; 95% CI: 1.21-1.77; p < .001). Moreover, PPM was associated with higher late mortality when Cox proportional-hazards regression (HR: 1.97; 95% CI: 1.57-2.47; p < .001) and propensity score (HR: 1.99; 95% CI: 1.34-2.95; p < .001) adjusted data were pooled. Contrarily, moderate (HR: 1.01; 95% CI: 0.84-1.22; p = .88) or severe (HR: 1.19; 95% CI: 0.89-1.58; p = .24) PPM were not related to higher late mortality when adjusted data were pooled individually. PPM was associated with higher systolic pulmonary pressures (mean difference: 7.88 mmHg; 95% CI: 4.72-11.05; p < .001) and less pulmonary hypertension regression (OR: 5.78; 95% CI: 3.33-10.05; p < .001) late after surgery. CONCLUSIONS: Mitral valve PPM is associated with higher postoperative pulmonary artery pressure and might impair perioperative and overall survival. The relation should be further assessed in properly designed studies.

Do risk visualizations improve the understanding of numerical risks? A randomized, investigator-blinded general population survey.

BACKGROUND: Risk visualizations are often employed to support risk communication. However, their effectiveness in communication of single absolute risks remains unclear. We investigated the effectiveness of risk visualizations in conveying verbatim knowledge of single absolute risks among the general population. METHODS: Randomly sampled members of the general Dutch population completed four basic risk conversions from percentages to natural frequencies and vice versa. By random investigator-blinded allocation, these conversions were supported by either icon arrays, pie charts, bar graphs or no visualization. Verbatim risk knowledge was scored as the number of conversions completed correctly. RESULTS: 393 subjects were included. Overall, 60% of respondents answered all four questions correctly. Risk format (percentages vs. natural frequencies, p = 0.677) and risk magnitude (p = 0.532) were not associated with verbatim risk knowledge score. Younger age (p = 0.001) and higher education level (p < 0.001) were independently associated with higher scores. The use of risk visualizations was not associated with higher scores (OR = 1.08; 95% confidence interval: 0.69-1.69; p = 0.745). All three forms of risk visualization were equally ineffective. These findings held when stratifying by risk format, risk magnitude and user preference for a certain form of risk visualization. There were no significant interactions with age or education level. CONCLUSION: Risk visualizations did not improve conveyance of verbatim knowledge of single absolute risks, irrespective of age, education level, risk magnitude, risk format and form of risk visualization. Risk visualizations may therefore be less suitable for settings in which detailed conveyance of single absolute risks is the main objective, although their effect on user experience and perception of risk communication and subsequent patient activation and participation remains to be elucidated.

Outcome after surgical repair of tetralogy of Fallot: A systematic review and meta-analysis.

INTRODUCTION: Tetralogy of Fallot (TOF) is the most common cyanotic congenital heart disease. Intracardiac correction was pioneered by Walton Lillehei in 1955 and has since then gone through major developments. The aim of this study was to provide a systematic literature review of published results on the long-term outcome of complete surgical correction of TOF. METHODS: MEDLINE, PubMed, Embase, Web of Science, Cochrane, and Google Scholar were systematically searched for literature published between January 2000 and July 2018. Pooled estimates with a random effects model after log-transformation were calculated for mortality and reintervention. Potential heterogeneity was assessed by subgroup analyses and meta-regression. RESULTS: A total of 143 papers of 137 distinct cohorts comprising 21,427 patients and total follow-up duration of 147,430 patient-years were included. Overall mean age at correction was 3.7 ± 5.6 years, but excluding papers exclusively focusing on correction in adults yielded a mean age of 0.5 ± 2.5 years at correction. Previous palliative shunts (107 studies), a transventricular approach (81 studies), and a transannular patch (124 studies) were used in 16% (range 0%-78%), 39% (range 0%-100%), and 49% (range 0%-100%) of the patients. respectively. In case a transannular patch was used, monocusp reconstruction was applied in 15% (range 0%-100%) (49 studies). The most common genetic abnormality was Down syndrome, with a pooled estimated prevalence of 4.6% (range 0%-12.3%). The pooled estimates of early and late mortality were 2.84% (95% confidence interval [CI], 2.34-3.45) and 0.42%/year (95% CI, 0.33-0.54), respectively. The pooled estimate of late cardiac mortality was 0.26%/year (95% CI, 0.21-0.34). Valve-related mortality and non-valve-related mortality had pooled estimates of 0.20%/year (95% CI, 0.15-0.26) and 0.17%/year (95% CI, 0.12-0.22), respectively. The pooled estimate of reintervention was 2.26%/year (95% CI, 1.86-2.75). CONCLUSIONS: TOF can be surgically corrected at a young age with low perioperative and long-term mortality. Life-long intensive follow-up and substantial reintervention rates characterize the clinical course.

Outcomes after surgery for functional tricuspid regurgitation: a systematic review and meta-analysis.

AIMS: This study aims to provide a contemporary overview of outcomes after tricuspid valve (TV) surgery for functional tricuspid regurgitation (TR). METHODS AND RESULTS: The literature was systematically searched for papers published between January 2005 and December 2017 reporting on clinical/echocardiographic outcomes after TV surgery for functional TR. A random effects meta-analysis was conducted for outcome variables, and late outcomes are visualized by pooled Kaplan-Meier curves. Subgroup analyses were performed for studies with a within-study comparison of suture vs. ring repair and flexible vs. rigid ring repair. Eighty-seven publications were included, encompassing 13 184 patients (mean age: 62.1 ± 11.8 years, 55% females). A mitral valve procedure was performed in 92% of patients. Pooled mean follow-up was 4.0 ± 2.8 years. Pooled early mortality was 3.9% (95% CI: 3.2-4.6), and late mortality rate was 2.7%/year (95% CI: 2.0-3.5), of which approximately half was cardiac-related 1.2%/year (95% CI: 0.8-1.9). Pooled risk of early moderate-to-severe TR at discharge was 9.4% (95% CI: 7.0-12.1). Late moderate-to-severe TR rate after discharge was 1.9%/year (95% CI: 1.0-3.5). Late reintervention rate was 0.3%/year (95% CI: 0.2-0.4). Mortality and overall (early and late) TR rate were comparable between suture vs. ring annuloplasty (14 studies), whereas overall TR rate was higher after flexible ring vs. rigid ring annuloplasty (6 studies) (7.5%/year vs. 3.9%/year, P = 0.002). CONCLUSION: This study shows that patients undergoing surgery for functional tricuspid regurgitation (FTR) have an acceptable early and late mortality. However, TR remains prevalent after surgery. The results of this study can be used to inform patients and clinicians about the expected outcome after surgery for FTR and can results serve as a benchmark for the performance of emerging transcatheter TV interventions.

Clinical and quality of life outcomes after aortic valve replacement and aortic root surgery in adult patients <65 years old.

Selecting the optimal surgical treatment strategy in patients below the age of 65 years (i.e., non-elderly patients) with aortic valve or aortic root disease remains challenging. The objective of the current study is to summarize contemporary research on clinical and quality of life outcomes after aortic valve replacement (AVR) and aortic root surgery in non-elderly patients. Recent systematic reviews on clinical outcome after biological and mechanical AVR, the Ross procedure and aortic root surgery show that event occurrence is considerable after any type of AVR or aortic root surgery and-with the exception of the Ross procedure-survival is suboptimal. Although thromboembolism and bleeding events are more common after mechanical AVR and root surgery, these events are also considerably present after biological AVR, the Ross procedure and valve-sparing aortic root surgery (VSRR). Similarly, reoperation is more common after biological AVR, the Ross procedure and VSRR, but also occurs frequently after mechanical AVR and root replacement. Published evidence in AVR patients points to the direction of better health-related quality of life (HRQoL) outcomes with a biological solutions, while the HRQoL after aortic root surgery is limited and contradictory. This review illustrates that treatment for non-elderly aortic valve and aortic root disease patients needs to be tailored to the individual patient, considering both clinical and HRQoL outcomes as crucial factors to reach a treatment decision that best reflects the patient's values and goals in life.

Bioprosthetic Aortic Valve Replacement in Nonelderly Adults: A Systematic Review, Meta-Analysis, Microsimulation

Background To support decision-making in aortic valve replacement in nonelderly adults, we aim to provide a comprehensive overview of reported outcome after bioprosthetic aortic valve replacement and to translate this to age-specific patient outcome estimates. Methods and Results A systematic review was conducted for papers reporting clinical outcome after aortic valve replacement with currently available bioprostheses in patients with a mean age <55 years, published between January 1, 2000, and January 9, 2016. Pooled reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risk for the ages of 25, 35, 45, and 55 years at surgery. Nineteen publications were included, encompassing a total of 2686 patients with 21 117 patient-years of follow-up (pooled mean follow-up: 7.9±4.2 years). Pooled mean age at surgery was 50.7±11.0 years. Pooled early mortality risk was 3.30% (95% CI, 2.39-4.55), late mortality rate was 2.39%/y (95% CI, 1.13-2.94), reintervention 1.82%/y (95% CI, 1.31-2.52), structural valve deterioration 1.59%/y (95% CI, 1.21-2.10), thromboembolism 0.53%/y (95% CI, 0.42-0.67), bleeding 0.22%/y (95% CI, 0.16-0.32), endocarditis 0.48%/y (95% CI, 0.37-0.62), and 20-year pooled actuarial survival was 58.7% and freedom from reintervention was 29.0%. Median time to structural valve deterioration was 17.3 years and median time to all-cause first reintervention was 16.9 years. For a 45-year-old adult, for example, this translated to a microsimulation-based estimated life expectancy of 21 years (general population: 32 years) and lifetime risk of reintervention of 78%, structural valve deterioration 71%, thromboembolism 12%, bleeding 5%, and endocarditis 9%. Conclusions Aortic valve replacement with bioprostheses in young adults is associated with high structural valve deterioration and reintervention rates and low, though not absent, hazards of thromboembolism and bleeding. Foremostly, most patients will require one or more reinterventions during their lifetime and survival is impaired in comparison with the age- and sex-matched general population. Prosthesis durability remains the main concern in nonelderly patients.

What Is the Potential of Tissue-Engineered Pulmonary Valves in Children?

BACKGROUND: As a living heart valve substitute with growth potential and improved durability, tissue-engineered heart valves (TEHVs) may prevent reinterventions that are currently often needed in children with congenital heart disease. We performed early health technology assessment to assess the potential cost-effectiveness of TEHVs in children requiring right ventricular outflow tract reconstruction (RVOTR). METHODS: A systematic review and meta-analysis was conducted of studies reporting clinical outcome after RVOTR with existing heart valve substitutes in children (mean age ≤12 years or maximum age ≤21 years) published between January 1, 2000, and May 2, 2018. Using a patient-level simulation model, costs and effects of RVOTR with TEHVs compared with existing heart valve substitutes were assessed from a health care perspective applying a 10-year time horizon. Improvements in performance of TEHVs, divided in durability, thrombogenicity, and infection resistance, were explored to estimate quality-adjusted life year (QALY) gain, cost reduction, headroom, and budget impact associated with TEHVs. RESULTS: Five-year freedom from reintervention after RVOTR with existing heart valve substitutes was 46.1% in patients less than or equal to 2 years of age and 81.1% in patients greater than 2 years of age. Improvements in durability had the highest impact on QALYs and costs. In the improved TEHV performance scenario (durability ≥5 years and -50% other valve-related events), QALY gain was 0.074 and cost reduction was €10,378 per patient, translating to maximum additional costs of €11,856 per TEHV compared with existing heart valve substitutes. CONCLUSIONS: This study showed that there is room for improvement in clinical outcomes in children requiring RVOTR. If TEHVs result in improved clinical outcomes, they are expected to be cost-effective compared with existing heart valve substitutes.

Bioprosthetic aortic valve replacement in elderly patients: Meta-analysis and microsimulation.

OBJECTIVE: To support decision-making in aortic valve replacement (AVR) in elderly patients, we provide a comprehensive overview of outcome after AVR with bioprostheses. METHODS: A systematic review was conducted of studies reporting clinical outcome after AVR with bioprostheses in elderly patients (mean age ≥70 years; minimum age ≥65 years) published between January 1, 2000, to September 1, 2016. Reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risks. RESULTS: Forty-two studies reporting on 34 patient cohorts were included, encompassing a total of 12,842 patients with 55,437 patient-years of follow-up (pooled mean follow-up 5.0 ± 3.3 years). Pooled mean age was 76.5 ± 5.5 years. Pooled early mortality risk was 5.42% (95% confidence interval [CI], 4.49-6.55), thromboembolism rate was 1.83%/year (95% CI, 1.28-3.61), and bleeding rate was 0.75%/year (95% CI, 0.50-1.11). Structural valve deterioration (SVD) was based on pooled time to SVD data (Gompertz; shape: 0.124, rate: 0.003). For a 75-year-old patient, this translated to an estimated life expectancy of 9.8 years (general population: 10.2 years) and lifetime risks of bleeding of 7%, thromboembolism of 17%, and reintervention of 9%. CONCLUSIONS: The low risks of SVD and reintervention support the use of bioprostheses in elderly patients in need of AVR. The estimated life expectancy after AVR was comparable with the general population. The results of this study inform patients and clinicians about the expected outcomes after bioprosthetic AVR and thereby support treatment decision-making. Furthermore, our results can be used as a benchmark for long-term outcomes after transcatheter aortic valve implantation in patients who were eligible for surgery and other (future) alternative treatments (eg, tissue-engineered heart valves).

The Ross Procedure: A Systematic Review, Meta-Analysis, and Microsimulation.

BACKGROUND: To support decision-making in aortic valve replacement in children and adults, we provide a comprehensive overview of outcome after the Ross procedure. METHODS AND RESULTS: A systematic search was conducted for publications reporting clinical outcome after the Ross procedure, published between January 1, 2000, and November 22, 2017. Reported event rates and time-to-event data were pooled and entered into a microsimulation model to calculate life expectancy and lifetime event risk. Ninety-nine publications were included (13 129 patients; total follow-up: 93 408 patient-years, pooled mean follow-up: 7.9±5.3 years). Pooled mean age at surgery was 9.4±5.5 years for children and 41.9±11.4 for adults. For children and adults, respectively, pooled early mortality risk was 4.19% (95% CI, 3.21-5.46) and 2.01% (95% CI, 1.44-2.82), late mortality rate was 0.54%/y (95% CI, 0.42-0.70) and 0.59%/y (95% CI, 0.46-0.76), autograft reintervention 1.28%/y (95% CI, 0.99-1.66) and 0.83%/y (95% CI, 0.68-1.01), and right ventricular outflow tract reintervention 1.97%/y (95% CI, 1.64-2.36) and 0.47%/y (95% CI, 0.37-0.59). Pooled thromboembolism and bleeding rates were low and comparable to the general population. Lifetime risks of autograft and right ventricular outflow tract reintervention were, respectively, 94% and 100% for children and 49% and 19% for a 45-year-old. Estimated life expectancy after surgery was 59 years for children (general population: 64 years) and 30 years for a 45 years old (general population: 31 years). CONCLUSIONS: Through excellent survival and avoidance of the burden of anticoagulation, the Ross procedure provides a unique opportunity for patients whose preferences do not align with the outcome provided by mechanical valve replacement and for growing children who also benefit from autograft diameter increase along with somatic growth. On the downside, almost all pediatric and many adult Ross patients will require a reintervention in their lifetime.

Patient and physician view on patient information and decision-making in congenital aortic and pulmonary valve surgery.

Background: To assess the current state of patient information and decision-making in congenital aortic and pulmonary valve disease, we conducted a survey among patients, parents and physicians. Methods: A questionnaire was sent by ground mail to 157 adults and 32 parents of children who previously underwent surgery for congenital aortic or pulmonary valve disease at 0-40 years of age between January 2005 and February 2014 at the Erasmus University Medical Center and to all paediatric and adult congenital cardiologists and congenital cardiac surgeons in the Netherlands (n=88). Results: 73 patients/parents (39% response rate, 62 adult patients, 11 parents of paediatric patients) and 35 physicians (40% response rate) responded. Median patient age at the time of surgery was 25.7 years. Basic disease-specific knowledge was adequate in 42% of patients/parents and numeracy was sufficient in 47%. Patients/parents reported that they rely heavily on their physicians for information and often experience difficulty in finding reliable information elsewhere. They lack information on psychosocial aspects of disease (29% of respondents) and risks and benefits of treatment options (26%). They feel less involved in decision-making than they would prefer to be (p=0.014). Decisional conflict at the time of surgery was experienced by 31% of patients/parents. If they had to do it again, 72% of patients/parents would want the same treatment. Quality of life is often impaired due to various valve-related anxieties and lifestyle changes. Physicians reported that they are unable to fully inform and sufficiently involve patients, due to limited patient/parent knowledge and understanding (56%) and limited time during consultations (32%). Patients/parents (98%) and physicians (97%) agree that they should have shared roles in decision-making. Conclusion: The substantial shortcomings in our current practice of patient information and decision-making underline the need for innovative solutions, such as careful implementation of patient information tools and shared decision-making in the care path.

Decellularized Versus Standard Pulmonary Allografts in the Ross Procedure: Propensity-Matched Analysis.

BACKGROUND: It is hypothesized that decellularization of allografts used for right ventricular outflow tract reconstruction may result in decreased valve deterioration. This study compared the durability of fresh decellularized pulmonary allografts with standard cryopreserved pulmonary allografts in patients undergoing the Ross procedure. METHODS: The Ross procedure was performed in 144 patients with decellularized allografts (DA) from 2005 to 2014 and in 619 with standard cryopreserved allografts (SCA) from 1990 to 2014. Propensity score matching was used to compare early and midterm clinical outcome and echocardiographic allograft function over time between the two groups. RESULTS: We matched 94 DA patients (79.3% male; median age, 34.0 years; mean follow-up, 2.4 ± 1.9 years) to 94 SCA patients (78.3% male; median age, 35.0 years; mean follow-up, 9.4 ± 4.2 years). There were no significant differences in baseline characteristics after matching. The matched DA vs SCA groups, respectively, were comparable in actuarial 5-year freedom from allograft dysfunction (85.6% [95% confidence interval {CI}, 53.9% to 96.2%] vs 93.3% [95% CI, 85.7% to 96.9%], p = 0.892), freedom from allograft reintervention (98.8% [95% CI, 91.7% to 99.8%] vs 95.5% [95% CI, 88.5% to 98.3%], p = 0.383), survival (95.3% [95% CI, 87.8% to 98.2%] vs 97.7% [95% CI, 91.3% to 99.4%], p = 0.323), and event-free survival (83.5% [95% CI, 70.6% to 91.1%] vs 84.5% [95% CI, 75.2% to 90.5%], p = 0.515). Longitudinal echocardiographic analyses showed a similarly modest increase in allograft gradient and regurgitation grades over time in both groups, although direct statistical comparison was not possible. CONCLUSIONS: Up to 5 years of follow-up, DA and SCA used for right ventricular outflow tract reconstruction in the Ross procedure are associated with comparably excellent clinical and hemodynamic outcome. Longer follow-up and dedicated echocardiographic studies will shed light on the long-term performance of DAs.

Mechanical aortic valve replacement in non-elderly adults: meta-analysis and microsimulation.

AIMS: To support decision-making regarding prosthetic valve selection in non-elderly adults, we aim to provide a detailed overview of outcome after contemporary mechanical aortic valve replacement (AVR). METHODS AND RESULTS: A systematic review was conducted for papers reporting clinical outcome after AVR with bileaflet mechanical valves with a mean patient age ≥18 and ≤55 years, published between 1 January 1995 and 31 December 2015. Through meta-analysis outcomes were pooled and entered into a microsimulation model to calculate (event-free) life expectancy and lifetime event risk. Twenty-nine publications, encompassing a total of 5728 patients with 32 515 patient-years of follow-up (pooled mean follow-up: 5.7 years), were included. Pooled mean age at surgery was 48.0 years. Pooled early mortality risk was 3.15% (95% confidence interval (CI):2.37-4.23), late mortality rate was 1.55%/year (95%CI:1.25-1.92); 38.7% of late deaths were valve-related. Pooled thromboembolism rate was 0.90%/year (95%CI:0.68-1.21), major bleeding 0.85%/year (95%CI:0.65-1.12), nonstructural valve dysfunction 0.39%/year (95%CI:0.21-0.76), endocarditis 0.41%/year (95%CI:0.29-0.57), valve thrombosis 0.14%/year (95%CI:0.08-0.25), structural valve deterioration 0.00%/year (zero events observed), and reintervention 0.51%/year (95%CI:0.37-0.71), mostly due to nonstructural valve dysfunction and endocarditis. For a 45-year-old, for example, this translated to an estimated life expectancy of 19 years (general population: 34 years) and lifetime risks of thromboembolism, bleeding and reintervention of 18%, 15%, and 10%, respectively. CONCLUSION: This study demonstrates that outcome after mechanical AVR in non-elderly adults is characterized by suboptimal survival and considerable lifetime risk of anticoagulation-related complications, but also reoperation. Non-elderly adult patients who are facing prosthetic valve selection are entitled to conveyance of evidence-based estimates of the risks and benefits of both mechanical and biological valve options in a shared decision-making process.

Decellularized Allografts for Right Ventricular Outflow Tract Reconstruction in Children.

OBJECTIVE: Determine the midterm outcomes of decellularized allografts for right ventricular outflow tract (RVOT) reconstruction in children less than 12 years of age. METHODS: The study included all consecutive patients submitted to RVOT reconstruction with decellularized allografts between June 2006 and June 2016. Besides clinical and echocardiographic control, 20 patients with more than five years of follow-up were evaluated with computed tomography (CT) scans to determine allograft diameters and calcium scores. Structural valve deterioration was defined as any peak gradient above 40 mm Hg and/or insufficiency of moderate or severe degree. Conduit failure was defined as the need for allograft reintervention. RESULTS: There were 59 patients with a median age of six years (range = 0.01-12 years). The most common operation was the Ross procedure (34%). Mean clinical follow-up was 5.4 (2.8) years and was 94% complete. At eight years, only two patients needed a reintervention, with a 90.9% freedom from this event. Structural valve deterioration occurred in 13 patients, 5 due to stenosis and 8 due to insufficiency, with a freedom from structural valve deterioration due to any cause of 64.9% at eight years. Late CT scans demonstrated the absence or minimal calcification of the conduits. CONCLUSIONS: Decellularized allografts for RVOT reconstruction in children were associated with a low incidence of structural valve deterioration and conduit failure. Although these results still need to be confirmed in larger series and with longer follow-up, our data suggest favorable outcomes, at least in the first decade after the operation.