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.

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.

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.

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.

For a structured response to the psychosocial consequences of the restrictive measures imposed by the global COVID-19 health pandemic: the MAVIPAN longitudinal prospective cohort study protocol.

INTRODUCTION: The COVID-19 pandemic and associated restrictive measures have caused important disruptions in economies and labour markets, changed the way we work and socialise, forced schools to close and healthcare and social services to reorganise. This unprecedented crisis forces individuals to make considerable efforts to adapt and will have psychological and social consequences, mainly on vulnerable individuals, that will remain once the pandemic is contained and will most likely exacerbate existing social and gender health inequalities. This crisis also puts a toll on the capacity of our healthcare and social services structures to provide timely and adequate care. The MAVIPAN (Ma vie et la pandémie/ My Life and the Pandemic) study aims to document how individuals, families, healthcare workers and health organisations are affected by the pandemic and how they adapt. METHODS AND ANALYSIS: MAVIPAN is a 5-year longitudinal prospective cohort study launched in April 2020 across the province of Quebec (Canada). Quantitative data will be collected through online questionnaires (4-6 times/year) according to the evolution of the pandemic. Qualitative data will be collected with individual and group interviews and will seek to deepen our understanding of coping strategies. Analysis will be conducted under a mixed-method umbrella, with both sequential and simultaneous analyses of quantitative and qualitative data. ETHICS AND DISSEMINATION: MAVIPAN aims to support the healthcare and social services system response by providing high-quality, real-time information needed to identify those who are most affected by the pandemic and by guiding public health authorities' decision making regarding intervention and resource allocation to mitigate these impacts. MAVIPAN was approved by the Ethics Committees of the Primary Care and Population Health Research Sector of CIUSSS de la Capitale-Nationale (Committee of record) and of the additional participating institutions. TRIAL REGISTRATION NUMBER: NCT04575571.

Implementation of a new clinical and organisational practice to improve access to primary care services: a protocol for an effectiveness-implementation hybrid study.

INTRODUCTION: In Canada, as in most Organisation for Economic Co-operation and Development countries, healthcare systems face significant challenges in ensuring better access to primary care. A regional healthcare organisation in Quebec (Canada) serving a population of approximately 755 459 citizens has implemented a standardised access approach to primary care services for this population. The objective of this new clinical and organisational practice is to ensure that users benefit from the same referral process, regardless of the entry point, in order to be directed to the right services. This new practice integrates a shared decision-making process between the user and the professional, and a collaborative process between different health professionals within and between services. The objective of our research is to identify and characterise the conditions of implementation of this practice. METHODS: This effectiveness-implementation hybrid investigation will use an embedded single-case study, defined in this case as the process of implementing a clinical and organisational practice within a healthcare organisation. Further to an evaluation conducted during a preliminary phase of the project, this study consists of evaluating the implementation of this new practice in four medical clinics (family medicine groups). A qualitative analysis of the data and a quantitative preimplementation and postimplementation analysis based on performance indicators will be conducted. This study is ultimately situated within a participatory organisational approach that involves various stakeholders and users at each step of the implementation and evaluation process. 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 (#2020-1800). 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.

Confirmation of Aortic Stenosis Severity in Case of Discordance Between Aortic Valve Area and Gradient.

In this report, we illustrate the different flow-gradient patterns of aortic stenosis associated with discordant grading of stenosis severity at transthoracic echocardiography (TTE). The discordance among TTE parameters (mean gradient and aortic area) can be reconciled and true severity can be confirmed by ruling out potential measurements errors and by using multimodality imaging. (Level of Difficulty: Advanced.).

In vitro Doppler versus catheter transvalvular pressure gradients in balloon-expandable versus self-expanding transcatheter aortic valves.

OBJECTIVES: The objective of this in vitro study was to compare Doppler versus catheter transvalvular pressure gradients (TPG) in third generations balloon-expandable (BE) versus self-expanding (SE) transcatheter heart valves (THV). BACKGROUND: TPG is a key parameter to assess and follow valve hemodynamic function following transcatheter aortic valve implantation (TAVI). It remains uncertain and debated whether, and to which extent, TPGs differ according to the type of THV, that is, BE versus SE and to the method used for TPG measurement, that is, Doppler echocardiography versus cardiac catheterization. METHODS: The CoreValve EVOLUT PRO 26 mm and the SAPIEN 3 23 mm THVs were tested in a left heart simulator using a 21 mm aortic annulus under following conditions: heart rate: 70 bpm, mean aortic pressure: 100 mmHg, stroke volume: 30, 70 and 100 ml. Mean TPGs were measured by continuous-wave Doppler and by micro-tip pressure catheters positioned in the left ventricle and at 50 mm downstream to the tip of the THV leaflets. RESULTS: Doppler TPGs (9.5 ± 3.9 mmHg) were on average 40.5 ± 13.9% higher (p < 0.001) than catheter TPGs (6.3 ± 3.4 mmHg). Both Doppler and catheter TPGs were lower (p = 0.003) in the SE versus BE THVs (Doppler: 8.7 ± 3.5 vs. 10.7 ± 4.6; catheter: 5.0 ± 1.7 mmHg vs. 7.1 ± 2.2). The Doppler versus catheter difference in TPG increased with the higher flow conditions. The Doppler versus catheter difference in TPG was similar in BE versus SE THVs (3.6 ± 1.1 vs. 3.7 ± 1.4 mmHg or 42 ± 9 vs. 47 ± 9%; p = 0.58) overall and in each flow conditions. CONCLUSION: The Doppler TPGs are, on average, 40% higher than the catheter TPGs for both BE and SE THVs. The SE THV had lower Doppler and catheter TPGs compared to the BE THV, at normal and high flow states. The absolute and percent differences between Doppler versus catheter TPGs were similar in BE versus SE THVs.

Cardiac Damage Staging Classification in Asymptomatic Moderate or Severe Primary Mitral Regurgitation.

Background: Optimal timing for intervention remains uncertain in asymptomatic patients with primary mitral regurgitation (MR). We aimed to assess the prognostic value of a new cardiac damage staging classification in patients with asymptomatic moderate or severe primary MR. Methods: Clinical, Doppler-echocardiographic, and outcome data prospectively collected in 338 asymptomatic patients (64 ± 15 years, 68% men) with at least moderate primary MR were retrospectively analyzed. Patients were hierarchically classified as per the following staging classification: no cardiac damage (stage 0), mild left ventricular or left atrial damage (stage 1), moderate or severe left ventricular or left atrial damage (stage 2), pulmonary vasculature or tricuspid valve damage (stage 3), or right ventricular damage (stage 4). Results: There was a stepwise increase in 10-year mortality rates as per cardiac damage stage: 20.0% in stage 0, 25.6% in stage 1, 31.5% in stage 2, and 61.3% in stage 3-4 (p < 0.001). The staging classification was significantly associated with increased risk of mortality (hazard ratio = 1.41 per one-stage increase, 95% confidence interval: 1.07-1.85, p = 0.015) and the composite of cardiovascular mortality or hospitalization (hazard ratio = 1.51 per one-stage increase, 95% confidence interval: 1.07-2.15, p = 0.020) in multivariable analysis adjusted for EuroSCORE II, mitral valve intervention as a time-dependent variable, and other risk factors. The proposed scheme showed incremental value over several clinical variables (net reclassification index = 0.40, p = 0.03). Conclusions: The new staging classification provides independent and incremental prognostic value in patients with asymptomatic moderate or severe MR.