Durability of transcatheter aortic valve implantation.

Transcatheter aortic valve implantation (TAVI) is now utilised as a less invasive alternative to surgical aortic valve replacement (SAVR) across the whole spectrum of surgical risk. Long-term durability of the bioprosthetic valves has become a key goal of TAVI as this procedure is now considered for younger and lower-risk populations. The purpose of this article is to present a state-of-the-art overview on the definition, aetiology, risk factors, mechanisms, diagnosis, clinical impact, and management of bioprosthetic valve dysfunction (BVD) and failure (BVF) following TAVI with a comparative perspective versus SAVR. Structural valve deterioration (SVD) is the main factor limiting the durability of the bioprosthetic valves used for TAVI or SAVR, but non-structural BVD, such as prosthesis-patient mismatch and paravalvular regurgitation, as well as valve thrombosis or endocarditis may also lead to BVF. The incidence of BVF related to SVD or other causes is low (<5%) at midterm (5- to 8-year) follow-up and compares favourably with that of SAVR. The long-term follow-up data of randomised trials conducted with the first generations of transcatheter heart valves also suggest similar valve durability in TAVI versus SAVR at 10 years, but these trials suffer from major survivorship bias, and the long-term durability of TAVI will need to be confirmed by the analysis of the low-risk TAVI versus SAVR trials at 10 years.

Lipoprotein(a) and Calcific Aortic Valve Stenosis Progression: A Systematic Review and Meta-Analysis.

Importance: There are currently no pharmacological treatments available to slow hemodynamic progression of aortic stenosis. Plasma lipoprotein(a) concentrations predict incident aortic stenosis but its association with hemodynamic progression is controversial. Objective: To determine the association between plasma lipoprotein(a) concentrations and hemodynamic progression in patients with aortic stenosis. Design, Settings and Participants: The study included patients with aortic stenosis from 5 longitudinal clinical studies conducted from March 2001 to March 2023 in Canada and the UK. Of 757 total patients, data on plasma lipoprotein(a) concentrations and rates of hemodynamic progression assessed by echocardiography were available for 710, who were included in this analysis. Data were analyzed from March 2023 to April 2024. Exposure: Cohort-specific plasma lipoprotein(a) concentration tertiles. Main Outcomes and Measures: Hemodynamic aortic stenosis progression on echocardiography as assessed by annualized change in peak aortic jet velocity, mean transvalvular gradient, and aortic valve area. Results: Among the included patients, 497 (70%) were male and 213 (30%) were female. The mean (SD) age was 65.2 (13.1) years. Patients in the top lipoprotein(a) tertile demonstrated 41% (estimate, 1.41; 95% CI, 1.13-1.75) faster progression of peak aortic jet velocity and 57% (estimate, 1.57; 95% CI, 1.18-2.10) faster progression of mean transvalvular gradient than patients in the bottom tertile. There was no evidence of heterogeneity across the individual cohorts. Progression of aortic valve area was comparable between groups (estimate, 1.23; 95% CI, 0.71-2.12). Similar results were observed when plasma lipoprotein(a) concentrations were treated as a continuous variable. Conclusions and Relevance: In this study, higher plasma lipoprotein(a) concentrations were associated with faster rates of hemodynamic progression in patients with aortic stenosis. Lowering plasma lipoprotein(a) concentrations warrants further investigation in the prevention and treatment of aortic stenosis.

Subclinical valve leaflet thrombosis following bioprosthetic aortic valve replacement.

PURPOSE OF REVIEW: Subclinical leaflet thrombosis (SLT) is often an incidental finding characterized by a thin layer of thrombus involving one, two or three leaflets, with typical appearance on multi-detector computed tomography (MDCT) of hypo-attenuating defect at the aortic side of the leaflet, also called hypo-attenuating leaflet thickening (HALT). SLT may occur following both transcatheter aortic replacement (TAVR) or biological surgical aortic valve replacement (SAVR). The aim of this review is to present an overview of the current state of knowledge on the incidence, diagnosis, clinical impact, and management of SLT following TAVR or SAVR. RECENT FINDINGS: SLT occurs in 10-20% of patients following TAVR and is somewhat more frequent than following SAVR (5-15%). SLT may regress spontaneously without treatment in about 50% of the cases but may also progress to clinically significant valve thrombosis in some cases. Oral anticoagulation with vitamin K antagonist is reasonable if SLT is detected by echocardiography and/or MDCT during follow-up and is generally efficient to reverse SLT. SLT is associated with mild increase in the risk of stroke but has no impact on survival. SLT has been linked with accelerated structural valve deterioration and may thus impact valve durability and long-term outcomes. SUMMARY: SLT is often an incidental finding on echocardiography or MDCT that occurs in 10-20% of patients following TAVR or 5-15% following biological SAVR and is associated with a mild increase in the risk of thrombo-embolic event with no significant impact on mortality but may be associated with reduced valve durability.

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin.

Cardiac troponin is extensively used as a biomarker in modern medicine due to its diagnostic capability for myocardial injury, as well as its predictive and prognostic value for cardiac diseases. However, heterophile antibodies, antitroponin antibodies, and macrotroponin complexes can be observed both in seemingly healthy individuals and patients with cardiac diseases, potentially leading to false positive or disproportionate elevation of cTn (cardiac troponin) assay results and introducing discrepancies in clinical interpretations with impact on medical management. In this review article, we describe the possible mechanisms of cTn release and the sources of variations in the assessment of circulating cTn levels. We also explore the pathophysiological mechanisms underlying antitroponin antibody development and discuss the influence exerted by macrotroponin complexes on the results of immunoassays. Additionally, we explore approaches to detect these complexes by presenting various clinical scenarios encountered in routine clinical practice. Finally, unsolved questions about the development, prevalence, and clinical significance of cardiac autoantibodies are discussed.

Multimarker Approach to Improve Risk Stratification of Patients Undergoing Transcatheter Aortic Valve Implantation.

Background: A blood multimarker approach may be useful to enhance risk stratification in patients undergoing TAVI. Objectives: The objective of this study was to determine the prognostic value of multiple blood biomarkers in transcatheter aortic valve implantation (TAVI) patients. Methods: In this prospective study, several blood biomarkers of cardiovascular function, inflammation, and renal function were measured in 362 patients who underwent TAVI. The cohort was divided into 3 groups according to the number of elevated blood biomarkers (ie, ≥ median value for the whole cohort) for each patient before the procedure. Survival analyses were conducted to evaluate the association between blood biomarkers and risk of adverse event following TAVI. Results: During a median follow-up of 2.5 (IQR: 1.9-3.2) years, 34 (9.4%) patients were rehospitalized for heart failure, 99 (27%) patients died, and 113 (31.2%) met the composite endpoint of all-cause mortality or heart failure rehospitalization. Compared to patients with 0 to 3 elevated biomarkers (referent group), those with 4 to 7 and 8 to 9 elevated biomarkers had a higher risk of all-cause mortality (HR: 1.54 [95% CI: 0.84-2.80], P = 0.16, and HR: 2.81 [95% CI: 1.53-5.15], P < 0.001, respectively) and of the composite endpoint (HR: 1.65 [95% CI: 0.95-2.84], P = 0.07, and HR: 2.67 [95% CI: 1.52-4.70] P < 0.001, respectively). Moreover, adding the number of elevated blood biomarkers into the clinical multivariable model provided significant incremental predictive value for all-cause mortality (Net Reclassification Index = 0.71, P < 0.001). Conclusions: An increasing number of elevated blood biomarkers is associated with higher risks of adverse clinical outcomes following TAVI. The blood multimarker approach may be helpful to enhance risk stratification in TAVI patients.

Leaflet Mechanical Stress in Different Designs and Generations of Transcatheter Aortic Valves: An in Vitro Study.

Background: It is unknown whether bioprostheses used for transcatheter aortic valve implantation will have similar long-term durability as those used for surgical aortic valve replacement. Repetitive mechanical stress applied to the valve leaflets, particularly during diastole, is the main determinant of structural valve deterioration. Leaflet mechanical stress cannot be measured in vivo. The objective of this in vitro/in silico study was thus to compare the magnitude and regional distribution of leaflet mechanical stress in old vs new generations of self-expanding (SE) vs balloon expandable (BE) transcatheter heart valves (THVs). Methods: A double activation simulator was used for in vitro testing of two generations of SE THV (Medtronic CoreValve 26 mm and EVOLUT PRO 26 mm) and two generations of BE THV (Edwards SAPIEN 23 mm vs SAPIEN-3 23 mm). These THVs were implanted within a 21-mm aortic annulus. A noncontact system based on stereophotogammetry and digital image correlation with high spatial and temporal resolution (2000 img/sec) was used to visualize the valve leaflet motion and perform the three-dimensional analysis. A finite element model of the valve was developed, and the leaflet deformation obtained from the digital image correlation analysis was applied to the finite element model to calculate local leaflet mechanical stress during diastole. Results: The maximum von Mises leaflet stress was higher in early vs new THV generation (p < 0.05) and in BE vs SE THV (p < 0.05): early generation BE: 2.48 vs SE: 1.40 MPa; new generation BE: 1.68 vs SE: 1.07 MPa. For both types of THV, the highest values of leaflet stress were primarily observed in the upper leaflet edge near the commissures and to a lesser extent in the mid-portion of the leaflet body, which is the area where structural leaflet deterioration most often occurs in vivo. Conclusions: The results of this in vitro/in silico study suggest that: i) Newer generations of THVs have ∼30% lower leaflet mechanical stress than the early generations; ii) For a given generation, SE THVs have lower leaflet mechanical stress than BE THVs. Further studies are needed to determine if these differences between new vs early THV generations and between SE vs BE THVs will translate into significant differences in long-term valve durability in vivo.

Situations of anomie and the health workforce crisis: Policy implications of a socially sensitive and inclusive approach to human resources.

Health systems in most jurisdictions are facing an unprecedented workforce crisis, manifesting as labour shortages, high staff turnover, and increasing rates of absenteeism and burnout. These issues affect professional and occupational groups in both health and social care and individuals at early and later stages of their career. The intensity and pervasiveness of the crisis suggests that it is a multicausal phenomenon. Studies have focused on the relationship between working environments and worker satisfaction and well-being. However, these are of limited use in understanding the deeper mechanisms behind the large-scale workforce crisis. The subjective experience of work, while rooted in a particular work context, is also shaped by broader social and cultural phenomena that put social norms and individuals' ability to conform to them in tension. The concept of anomie, initially developed by Durkheim and redefined by Merton, focuses on the way social norms that guide conduct and aspirations lose influence and become incompatible with each other or unsuited to contemporary work contexts. Understanding the workforce crisis from the perspective of anomie enables the development and implementation of novel policies based on co-production strategies where concerned publics engage collaboratively in framing the problem and searching for solutions.

Understanding the impacts of the COVID-19 pandemic on the care experiences of people with mental-physical multimorbidity: protocol for a mixed methods study.

BACKGROUND: Primary care and other health services have been disrupted during the COVID-19 pandemic, yet the consequences of these service disruptions on patients' care experiences remain largely unstudied. People with mental-physical multimorbidity are vulnerable to the effects of the pandemic, and to sudden service disruptions. It is thus essential to better understand how their care experiences have been impacted by the current pandemic. This study aims to improve understanding of the care experiences of people with mental-physical multimorbidity during the pandemic and identify strategies to enhance these experiences. METHODS: We will conduct a mixed-methods study with multi-phase approach involving four distinct phases. Phase 1 will be a qualitative descriptive study in which we interview individuals with mental-physical multimorbidity and health professionals in order to explore the impacts of the pandemic on care experiences, as well as their perspectives on how care can be improved. The results of this phase will inform the design of study phases 2 and 3. Phase 2 will involve journey mapping exercises with a sub-group of participants with mental-physical multimorbidity to visually map out their care interactions and experiences over time and the critical moments that shaped their experiences. Phase 3 will involve an online, cross-sectional survey of care experiences administered to a larger group of people with mental disorders and/or chronic physical conditions. In phase 4, deliberative dialogues will be held with key partners to discuss and plan strategies for improving the delivery of care to people with mental-physical multimorbidity. Pre-dialogue workshops will enable us to synthesize an prepare the results from the previous three study phases. DISCUSSION: Our study results will generate much needed evidence of the positive and negative impacts of the COVID-19 pandemic on the care experiences of people with mental-physical multimorbidity and shed light on strategies that could improve care quality and experiences.

Association between remnant cholesterol and progression of bioprosthetic valve degeneration.

AIMS: Remnant cholesterol (RC) seems associated with native aortic stenosis. Bioprosthetic valve degeneration may share similar lipid-mediated pathways with aortic stenosis. We aimed to investigate the association of RC with the progression of bioprosthetic aortic valve degeneration and ensuing clinical outcomes. METHODS AND RESULTS: We enrolled 203 patients with a median of 7.0 years (interquartile range: 5.1-9.2) after surgical aortic valve replacement. RC concentration was dichotomized by the top RC tertile (23.7 mg/dL). At 3-year follow-up, 121 patients underwent follow-up visit for the assessment of annualized change in aortic valve calcium density (AVCd). RC levels showed a curvilinear relationship with an annualized progression rate of AVCd, with increased progression rates when RC >23.7 mg/dL (P = 0.008). There were 99 deaths and 46 aortic valve re-interventions in 133 patients during a median clinical follow-up of 8.8 (8.7-9.6) years. RC >23.7 mg/dL was independently associated with mortality or re-intervention (hazard ratio: 1.98; 95% confidence interval: 1.31-2.99; P = 0.001). CONCLUSION: Elevated RC is independently associated with faster progression of bioprosthetic valve degeneration and increased risk of all-cause mortality or aortic valve re-intervention.

Evaluation of an interprofessional primary healthcare team as a new model of primary care in Quebec: a protocol for a type 2 effectiveness-implementation hybrid study.

INTRODUCTION: One family medicine group (FMG) in Quebec has commenced a 5-year pilot project, which is herein referred to as the Archimède model, to implement a patient-centred model based on interprofessional care and the optimal use of healthcare providers' practice scopes. A research project will be conducted to: (1) assess this model's effect on the FMG's operational performance, and its users' resource utilisation at the public health system level; (2) investigate its optimisation with respect to professional roles, interprofessional teamwork and patient-centredness and (3) document users' experience with the model. The aim of this article is to describe the protocol that will be used for this research. METHODS AND ANALYSIS: A hybrid implementation approach (type 2 model) will be used. We will collect both quantitative and qualitative data. Regarding the quantitative dimension, and because this is a single-unit intervention study, we will use either or both synthetic control methods and one-sample generalised linear models for analyses at the FMG level. To evaluate the broader impact of Archimède on the public health system, we will use mixed-effects models and propensity score matching methods. Regarding the qualitative research dimension, using an interpretative descriptive approach, we will document users' experience and identify the factors that optimise professional scopes of practice, collaborative practices and patient-centredness. We will conduct individual in-depth semistructured interviews with healthcare providers, administrative staff, stakeholders involved in the Archimède model implementation and patients. ETHICS AND DISSEMINATION: This study was approved by the Ethics Committee of the Sectoral Research in Population Health and Primary Care of the Centre intégré universitaire de santé et de services sociaux de la Capitale-Nationale (#2019-1503). The results of the investigation will be presented to the stakeholders involved in the advisory committees and at several scientific conferences. Manuscripts will be submitted to peer-reviewed journals.

Integrating Echocardiography Parameters With Explainable Artificial Intelligence for Data-Driven Clustering of Primary Mitral Regurgitation Phenotypes.

BACKGROUND: Primary mitral regurgitation (MR) is a heterogeneous clinical disease requiring integration of echocardiographic parameters using guideline-driven recommendations to identify severe disease. OBJECTIVES: The purpose of this preliminary study was to explore novel data-driven approaches to delineate phenotypes of MR severity that benefit from surgery. METHODS: The authors used unsupervised and supervised machine learning and explainable artificial intelligence (AI) to integrate 24 echocardiographic parameters in 400 primary MR subjects from France (n = 243; development cohort) and Canada (n = 157; validation cohort) followed up during a median time of 3.2 years (IQR: 1.3-5.3 years) and 6.8 (IQR: 4.0-8.5 years), respectively. The authors compared the phenogroups' incremental prognostic value over conventional MR profiles and for the primary endpoint of all-cause mortality incorporating time-to-mitral valve repair/replacement surgery as a covariate for survival analysis (time-dependent exposure). RESULTS: High-severity (HS) phenogroups from the French cohort (HS: n = 117; low-severity [LS]: n = 126) and the Canadian cohort (HS: n = 87; LS: n = 70) showed improved event-free survival in surgical HS subjects over nonsurgical subjects (P = 0.047 and P = 0.020, respectively). A similar benefit of surgery was not seen in the LS phenogroup in both cohorts (P = 0.70 and P = 0.50, respectively). Phenogrouping showed incremental prognostic value in conventionally severe or moderate-severe MR subjects (Harrell C statistic improvement; P = 0.480; and categorical net reclassification improvement; P = 0.002). Explainable AI specified how each echocardiographic parameter contributed to phenogroup distribution. CONCLUSIONS: Novel data-driven phenogrouping and explainable AI aided in improved integration of echocardiographic data to identify patients with primary MR and improved event-free survival after mitral valve repair/replacement surgery.

Comparing Health Workforce Policy during a Major Global Health Crisis: A Critical Conceptual Debate and International Empirical Investigation.

BACKGROUND: The health workforce is central to healthcare systems and population health, but marginal in comparative health policy. This study aims to highlight the crucial relevance of the health workforce and contribute comparative evidence to help improve the protection of healthcare workers and prevention of inequalities during a major public health crisis. METHODS: Our integrated governance framework considers system, sector, organizational and socio-cultural dimensions of health workforce policy. The COVID-19 pandemic serves as the policy field and Brazil, Canada, Italy, and Germany as illustrative cases. We draw on secondary sources (literature, document analysis, public statistics, reports) and country expert information with a focus on the first COVID-19 waves until the summer of 2021. RESULTS: Our comparative investigation illustrates the benefits of a multi-level governance approach beyond health system typologies. In the selected countries, we found similar problems and governance gaps concerning increased workplace stress, lack of mental health support, and gender and racial inequalities. Health policy across countries failed to adequately respond to the needs of HCWs, thus exacerbating inequalities during a major global health crisis. CONCLUSIONS: Comparative health workforce policy research may contribute new knowledge to improve health system resilience and population health during a crisis.

Clinical significance of myocardial contraction fraction in significant primary mitral regurgitation.

BACKGROUND: The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains a matter of debate. Myocardial contraction fraction (MCF) - the ratio of the left ventricular (LV) stroke volume to that of the myocardial volume - is a volumetric measure of LV myocardial shortening independent of size or geometry. AIM: To assess the relationship between MCF and outcome in patients with significant chronic primary MR due to prolapse managed in contemporary practice. METHODS: Clinical, Doppler-echocardiographic and outcome data prospectively collected in 174 patients (mean age 62 years, 27% women) with significant primary MR and no or mild symptoms were analysed. The impact of MCF< or ≥30% on cardiac events (cardiovascular death, acute heart failure or MV surgery) was studied. RESULTS: During an estimated median follow-up of 49 (22-77) months, cardiac events occurred in 115 (66%) patients. The 4-year estimates of survival free from cardiac events were 21±5% for patients with MCF <30% and 40±6% for those with ≥30% (P<0.001). MCF <30% was associated with a considerable increased risk of cardiac events after adjustment for established clinical risk factors, MR severity and current recommended class I triggers for MV surgery (adjusted hazard ratio: 2.33, 95% confidence interval: 1.51-3.58; P<0.001). Moreover, MCF<30% improved the predictive performance of models, with better global fit, reclassification and discrimination. CONCLUSIONS: MCF<30% is strongly associated with occurrence of cardiac events in patients with significant primary MR due to prolapse. Further studies are needed to assess the direct impact of MCF on patient management and outcomes.

The contribution of amyloid deposition in the aortic valve to calcification and aortic stenosis.

Calcific aortic valve disease (CAVD) and stenosis have a complex pathogenesis, and no therapies are available that can halt or slow their progression. Several studies have shown the presence of apolipoprotein-related amyloid deposits in close proximity to calcified areas in diseased aortic valves. In this Perspective, we explore a possible relationship between amyloid deposits, calcification and the development of aortic valve stenosis. These amyloid deposits might contribute to the amplification of the inflammatory cycle in the aortic valve, including extracellular matrix remodelling and myofibroblast and osteoblast-like cell proliferation. Further investigation in this area is needed to characterize the amyloid deposits associated with CAVD, which could allow the use of antisense oligonucleotides and/or isotype gene therapies for the prevention and/or treatment of CAVD.

Impact of sex and sex hormones on pathophysiology and progression of aortic stenosis in a murine model.

The lesions observed in AS have been shown to be sex specific, with women presenting extensive fibrotic remodeling while men developing more calcification deposit. We thus aimed to evaluate the influence of sex and sex hormones on the pathophysiology of aortic valve stenosis (AS) in our mouse model of AS. LDLr-/- ApoB100/100 IGF-II+/- mice (n = 210) were separated in six different groups: (1) intact male (IM), (2) intact female (IF), (3) castrated male (CM), (4) ovariectomized females (OF), (5) CM with testosterone supplementation (CMT), and (6) OF with 17ß-estradiol supplementation (OFE). Mice were fed a high-fat/high-sucrose/high-cholesterol diet for 6 months. Hemodynamic progression of AS was followed by transthoracic echocardiography (at 12 and 36 weeks) and analyzed in all mice alive at 36 weeks. Aortic valves were collected for histological and digital droplet PCR* analysis. Increases in peak velocity were comparable in IF and IM (24.2 ± 5.7 vs. 25.8 ± 5.3 cm/s; p = 0.68), but IF presented with less severe AS. Between the three groups of male mice, AS progression was more important in IM (increase in peak velocity: 24.2 ± 5.7 cm/s; p < 0.001) compared to CM (6.2 ± 1.4; p = 0.42), and CMT (15.1 ± 3.5; p = 0.002). In the three groups of female mice, there were no statistical differences in AS progression. Digital PCR analysis revealed an important upregulation of the osteogenic gene RunX2 in IM (p < 0.0001) and downregulation of the pro-calcifying gene ALPL in IF (p < 0.05). Male sex and testosterone play an important role in upregulation of pro-calcifying genes and hemodynamic progression of AS. However, female mice appeared to be protected against calcification, characterized by downregulation of pro-osteogenic genes, but presented a similar AS hemodynamic progression.

Significance of Left Ventricular Ejection Time in Primary Mitral Regurgitation.

The optimal timing for mitral valve (MV) surgery in asymptomatic patients with primary mitral regurgitation (MR) remains controversial. We aimed at evaluating the relation between left ventricular ejection time (LVET) and outcome in patients with moderate or severe chronic primary MR because of prolapse. Clinical, Doppler echocardiographic, and outcome data prospectively collected from 302 patients (median age 61 [54 to 74] years, 34% women) with moderate or severe primary MR were analyzed. Patients were retrospectively stratified by quartiles of LVET. The primary end point of the study was the composite of need for MV surgery or all-cause mortality. During a median follow-up time of 66 (25th to 75th percentile, 33 to 95) months, 178 patients reached the primary end point. Patients in the lowest quartile of LVET (<260 ms) were at high risk for adverse events compared with those in the other quartiles of LVET (global p = 0.005), whereas the rate of events was similar for the other quartiles (p = NS for all). After adjustment for clinical predictors of outcome, including age, gender, history of atrial fibrillation, MR severity, and current recommended triggers for MV surgery in asymptomatic primary MR, LVET <260 ms was associated with an increased risk of events (adjusted hazard ratio 1.49, 95% confidence interval 1.03 to 2.16, p = 0.033). In conclusion, we observed that shorter LVET is associated with increased risk of adverse events in patients with moderate or severe primary MR because of prolapse. Further studies are required to investigate whether shorter LVET has a direct effect on outcomes or is solely a risk marker in primary MR.