ABSTRACT
BACKGROUND: Left ventricular outflow tract (LVOT) obstruction is a source of morbidity in hypertrophic cardiomyopathy (HCM) and a life-threatening complication of transcatheter mitral valve replacement (TMVR) and transcatheter aortic valve replacement (TAVR). Available surgical and transcatheter approaches are limited by high surgical risk, unsuitable septal perforators, and heart block requiring permanent pacemakers. OBJECTIVES: The authors report the initial experience of a novel transcatheter electrosurgical procedure developed to mimic surgical myotomy. METHODS: We used septal scoring along midline endocardium (SESAME) to treat patients, on a compassionate basis, with symptomatic LVOT obstruction or to create space to facilitate TMVR or TAVR. RESULTS: In this single-center retrospective study between 2021 and 2023, 76 patients underwent SESAME. In total, 11 (14%) had classic HCM, and the remainder underwent SESAME to facilitate TMVR or TAVR. All had technically successful SESAME myocardial laceration. Measures to predict post-TMVR LVOT significantly improved (neo-LVOT 42 mm2 [Q1-Q3: 7-117 mm2] to 170 mm2 [Q1-Q3: 95-265 mm2]; P < 0.001; skirt-neo-LVOT 169 mm2 [Q1-Q3: 153-193 mm2] to 214 mm2 [Q1-Q3: 180-262 mm2]; P < 0.001). Among patients with HCM, SESAME significantly decreased invasive LVOT gradients (resting: 54 mm Hg [Q1-Q3: 40-70 mm Hg] to 29 mm Hg [Q1-Q3: 12-36 mm Hg]; P = 0.023; provoked 146 mm Hg [Q1-Q3: 100-180 mm Hg] to 85 mm Hg [Q1-Q3: 40-120 mm Hg]; P = 0.076). A total of 74 (97.4%) survived the procedure. Five experienced 3 of 76 (3.9%) iatrogenic ventricular septal defects that did not require repair and 3 of 76 (3.9%) ventricular free wall perforations. Neither occurred in patients treated for HCM. Permanent pacemakers were required in 4 of 76 (5.3%), including 2 after concomitant TAVR. Lacerations were stable and did not propagate after SESAME (remaining septum: 5.9 ± 3.3 mm to 6.1 ± 3.2 mm; P = 0.8). CONCLUSIONS: With further experience, SESAME may benefit patients requiring septal reduction therapy for obstructive hypertrophic cardiomyopathy as well as those with LVOT obstruction after heart valve replacement, and/or can help facilitate transcatheter valve implantation.
Subject(s)
Cardiomyopathy, Hypertrophic , Heart Valve Prosthesis Implantation , Myotomy , Ventricular Outflow Obstruction, Left , Ventricular Outflow Obstruction , Humans , Mitral Valve/surgery , Heart Valve Prosthesis Implantation/methods , Retrospective Studies , Cardiac Catheterization/methods , Ventricular Outflow Obstruction/etiology , Ventricular Outflow Obstruction/surgery , Treatment Outcome , Cardiomyopathy, Hypertrophic/complications , Myotomy/adverse effectsABSTRACT
BACKGROUND: Transcatheter pulmonary valve replacement (TPVR) in patients with a congenital or acquired abnormality resulting in enlarged right ventricular outflow tract (RVOT) is challenging and may preclude treatment with dedicated devices. We describe a technique using a physician-modified endograft to facilitate TPVR. METHODS: Six patients underwent physician-modified endograft-facilitated TPVR for severe symptomatic pulmonary insufficiency with enlarged RVOT. The fenestration was created in a commercially available endograft before implantation, which was then deployed from the dominant branch pulmonary artery into the RVOT, with the fenestration aligned with the ostium of the nondominant pulmonary artery. A covered stent was placed through the fenestration into the nondominant branch pulmonary artery, and a transcatheter heart valve was deployed within the endograft at the level of the original pulmonary valve. RESULTS: Four patients had tetralogy of Fallot, 1 had pulmonary atresia, and 1 had rheumatic valve disease. The RVOT/main pulmonary artery was severely enlarged (diameter, 44.2 [43.5-50.6] mm). All patients had reduced right ventricular (RV) function and dilated RVs (RV end-diastolic volume, 314 [235-316] mL). Successful endograft, covered stent, and transcatheter heart valve deployment were achieved in all cases without stent/valve embolization, vascular complications, or bleeding complications. At 30 days, 1 patient had mild pulmonary insufficiency, while others had none. The RV size measured by echocardiography was significantly reduced after TPVR (RV area, 34.4 [baseline] versus 29.0 [pre-discharge] versus 25.3 [30 days] cm2; P=0.03). During median follow-up of 221.5 (range, 29-652) days, there were no deaths or need for pulmonary valve reintervention. One patient developed severe tricuspid regurgitation due to entrapment of the anterior tricuspid leaflet by the endograft. The patient underwent successful tricuspid replacement and resection of the offending endograft with preservation of the pulmonary valve prosthesis. CONCLUSIONS: Simple fenestration of an off-the-shelf endograft and associated covered stent placement through the fenestration allows TPVR for patients with dysfunctional native or patch-repaired pulmonary valves and RVOT enlargement.
Subject(s)
Heart Valve Prosthesis Implantation , Heart Valve Prosthesis , Pulmonary Valve Insufficiency , Pulmonary Valve , Humans , Pulmonary Valve/diagnostic imaging , Pulmonary Valve/surgery , Cardiac Catheterization , Treatment Outcome , Heart Valve Prosthesis/adverse effects , Pulmonary Valve Insufficiency/diagnostic imaging , Pulmonary Valve Insufficiency/etiology , Pulmonary Valve Insufficiency/surgery , Stents/adverse effects , Retrospective Studies , Prosthesis DesignABSTRACT
OBJECTIVE: To help increase the confidence of both caregivers and clinicians in providing palliative care to adults with intellectual and developmental disabilities (IDD) using an easy-to-follow framework to improve and overcome barriers to effective palliative care in this population. QUALITY OF EVIDENCE: A literature review was conducted to explore recent best evidence to address these palliative care needs and to allow for a focused opportunity to consider the details of implementing clinical practice guidelines in the palliative care context. Evidence ranges from level I to level III. MAIN MESSAGE: Pain and psychological and emotional distress are important issues for individuals with IDD, as they can be difficult to assess and measure, and often present atypically, especially in those with limited communication skills. Further, little is known about end-of-life needs in the adult population with IDD, especially for those living in community residences. The conducted literature review of patient, caregiver, and clinician experiences exposed considerable barriers, including incorrect assumptions about patients' capacity to understand and discomfort of both caregivers and clinicians with open communication. This has resulted in exclusion of adults with IDD from their own care, which has proven harmful. Maximizing time in familiar surroundings and establishing trust and continuity are crucial. Sometimes trial and error with empiric use of comfort medications is necessary, but this can be mitigated with careful examination of distress patterns and judicious use of diagnostic testing. It is always best to integrate the palliative approach into the existing pattern of care. CONCLUSION: The validated tools and recommendations provided will assist with communication, symptom interpretation, treatment decisions, advanced care planning, addressing grief, and important considerations in end-of-life care.
Subject(s)
Health Services for Persons with Disabilities , Palliative Care/methods , Palliative Care/psychology , Persons with Mental Disabilities/psychology , Adult , Aged , Caregivers/psychology , Communication , Decision Making , Female , Humans , Male , Middle Aged , Physician-Patient RelationsSubject(s)
Comprehensive Health Care/methods , Developmental Disabilities/therapy , Health Services for Persons with Disabilities , Intellectual Disability/therapy , Patient-Centered Care/methods , Adult , Disability Evaluation , Family Practice/methods , Female , Humans , Male , Middle Aged , Physical Examination/methods , Risk Assessment/methods , Symptom Assessment/methodsABSTRACT
PROBLEM ADDRESSED: Adults with intellectual and developmental disabilities (IDD) are a complex population that could benefit from improved care coordination across health and social sectors, as they experience poorer health and have higher rates of emergency department use and hospitalization due to ambulatory care-sensitive conditions. OBJECTIVE OF PROGRAM: To pilot a novel, enhanced model of care coordination for complex patients with IDD. PROGRAM DESCRIPTION: Health Links is a provincial care-coordination program for patients with complex health care needs. This pilot program adapted Health Links to include a guide and training specific to adults with IDD to ensure that these patients' needs were met and high-quality, efficient care was provided. CONCLUSION: A tailored care-coordination approach for adults with IDD was able to identify complex patients in need and successfully bridge cross-sectoral care.
Subject(s)
Developmental Disabilities/therapy , Health Services for Persons with Disabilities/organization & administration , Intellectual Disability/therapy , Patient Care Management/methods , Adult , Canada , Female , Health Plan Implementation , Humans , Intersectoral Collaboration , Male , Middle Aged , Outcome and Process Assessment, Health Care , Pilot Projects , Program EvaluationABSTRACT
PROBLEM ADDRESSED: Adults with intellectual and developmental disabilities (IDD), a group with complex health problems and inequities in access to health care, look to family physicians for primary care. OBJECTIVE OF PROGRAM: To enable residents to learn and demonstrate competencies that are unique to the care of adults with IDD with minimal extra time and resources required of the residency program. PROGRAM DESCRIPTION: In their regular family medicine teaching practices, residents undertake planned encounters with adults with IDD involving comprehensive health assessments with physical examinations. Tools to implement the Canadian guidelines for primary care of adults with IDD are available to support the residents in their encounters. Background information in the form of self-learning and small group learning resources, field notes with rubrics to assess residents' development of competencies, and faculty development resources are also available. CONCLUSION: It is important to include such planned clinical experiences in family medicine residency curricula because people with IDD have special needs that are difficult to learn about in other settings. It is a benefit to residents to have patients and families actively contributing to teaching.
Subject(s)
Developmental Disabilities , Family Practice/education , Health Services for Persons with Disabilities , Intellectual Disability , Internship and Residency/methods , Physicians, Family/education , Adult , Canada , Clinical Competence , Curriculum , Female , Humans , Male , Physicians, Family/psychologyABSTRACT
OBJECTIVE: To update the 2011 Canadian guidelines for primary care of adults with intellectual and developmental disabilities (IDD). METHODS: Family physicians and other health professionals experienced in the care of people with IDD reviewed and synthesized recent empirical, ecosystem, expert, and experiential knowledge. A system was developed to grade the strength of recommendations. RECOMMENDATIONS: Adults with IDD are a heterogeneous group of patients and have health conditions and factors affecting their health that can vary in kind, manifestation, severity, or complexity from those of others in the community. They require approaches to care and interventions that are adapted to their needs. These guidelines provide advice regarding standards of care. References to clinical tools and other practical resources are incorporated. The approaches to care that are outlined here can be applied to other groups of patients that have impairments in cognitive, communicative, or other adaptive functioning. CONCLUSION: As primary care providers, family physicians play a vital role in promoting the health and well-being of adults with IDD. These guidelines can aid their decision making with patients and caregivers.
Subject(s)
Disabled Persons , Primary Health Care/standards , Standard of Care/organization & administration , Adult , Canada , Consensus , Developmental Disabilities , Humans , Intellectual DisabilityABSTRACT
OBJECTIF: Mettre à jour les Lignes directrices consensuelles canadiennes 2011 en matière de soins primaires aux adultes ayant une déficience développementale. MÉTHODES: Des médecins de famille et d'autres professionnels de la santé expérimentés dans les soins aux personnes ayant des DID ont examiné et synthétisé les récentes connaissances empiriques, d'écosystèmes, expertes et expérientielles. Un système a été conçu pour catégoriser la qualité des recommandations. RECOMMANDATIONS: Les adultes ayant des DID sont un groupe hétérogène de patients qui présentent des affections médicales et des facteurs qui influent sur leur santé, qui diffèrent de ceux qui touchent les autres membres de la communauté de par leur nature, leurs manifestations, leur gravité ou leur complexité. Ces personnes nécessitent une approche de soins et des interventions adaptées à leurs besoins. Les présentes lignes directrices offrent des conseils en matière de normes de soins. Nous avons incorporé des références à des outils cliniques et à d'autres ressources pratiques. Les approches de soins décrites ici s'appliquent aussi à d'autres groupes de patients ayant un déficit cognitif ou de la communication, ou d'autres déficits des fonctions adaptatives. CONCLUSION: À titre de fournisseurs de soins de première ligne, les médecins de famille jouent un rôle vital de promotion de la santé et de bien-être auprès des adultes ayant des DID. Ces lignes directrices peuvent les aider à prendre des décisions avec les patients et les aidants naturels.
ABSTRACT
OBJECTIVE: To delineate the factors inherent in caring for patients with intellectual and developmental disabilities (IDD) that lead to complexity and to provide perspectives and techniques mapped to the phases of the clinical encounter. SOURCES OF INFORMATION: The authors of the physical health section of the 2018 Canadian consensus guidelines on the primary care of adults with IDD consisted of family physicians, all of whom practise comprehensive family medicine with additional clinical experience in care of adults with IDD. These authors reviewed evidence on which their recommendations are based and these recommendations have undergone a rigorous peer review to ensure that they deserve special attention because they highlight what is different from what a family physician would consider to constitute "normal care" for the general population. MAIN MESSAGE: Additional factors across the phases of clinical encounters with patients with IDD include the need for the following: an initial assessment that identifies genetic or neurologic conditions to guide anticipatory care and isolates unique barriers to health promotion and chronic disease management; adaptations to history taking, particularly for patients who are unable to describe symptoms owing to cognitive and communication deficits; overcoming challenges to performing physical examinations and certain investigations; addressing uncertainty in the formulation of hypotheses to establish an appropriate diagnosis; and involvement of resources of the developmental services sector to provide a management plan as well as an adapted empathetic approach in order to integrate the patient's illness experience. CONCLUSION: Although each patient with IDD is unique, and care of patients with IDD requires knowledge of certain conditions, these considerations are readily identifiable, and family physicians as expert generalists are well equipped to provide excellent care to patients with IDD.
Subject(s)
Autism Spectrum Disorder/therapy , Intellectual Disability/therapy , Physician-Patient Relations , Primary Health Care/methods , Autism Spectrum Disorder/complications , Canada , Delivery of Health Care/standards , Female , Humans , Intellectual Disability/complications , Physical Examination/methods , Young AdultABSTRACT
OBJECTIVE: To provide primary care physicians with an understanding of the causes of behaviours that challenge (BTC) in adults with intellectual and developmental disabilities (IDD), as presented in the 2018 Canadian consensus guidelines for primary care of adults with IDD; to offer a systematic approach to the assessment and treatment of such behaviours; and to link to tools to support these assessments. SOURCES OF INFORMATION: This review elaborates upon guidelines 26 to 29 in the mental health section of the 2018 Canadian consensus guidelines. Several of the authors participated in the development of these guidelines, which were based on literature searches and interdisciplinary input. MAIN MESSAGE: Most adults with IDD are followed by primary care providers but they comprise a small proportion of primary care practices. Unique ways of communicating needs, diagnostic queries, and BTC are common in this population. This complexity can lead to missed diagnoses and inappropriate antipsychotic medication use with attendant risks. This article presents a systematic approach, HELP, to the assessment and treatment of factors of Health, Environment, Lived experience, and Psychiatric conditions that can lead to BTC and includes tools to support these assessments. CONCLUSION: A structured approach to the assessment and treatment of BTC in adults with IDD helps family physicians provide guideline-directed, individualized care to this population. This includes a systematic evaluation using the HELP framework that takes place over multiple visits. A team of health professionals might be needed for optimal care, but these resources are not routinely available across Canada.
Subject(s)
Developmental Disabilities/therapy , Intellectual Disability/therapy , Physical Examination/methods , Physician-Patient Relations , Primary Health Care/methods , Adult , Aggression/physiology , Canada , Communication , Female , Fragile X Syndrome/therapy , Humans , Practice Guidelines as Topic , Risk Assessment , Young AdultABSTRACT
OBJECTIVE: To provide tips and tools for primary care practitioners carrying out health checks for adult patients with intellectual and developmental disabilities (IDD) and for implementing a systematic program of health checks in a group or team practice. SOURCES OF INFORMATION: The "Primary Care of Adults with Intellectual and Developmental Disabilities. 2018 Canadian Consensus Guidelines" literature review and interdisciplinary input. Experience in implementing health checks in family practices was obtained through the primary care project of H-CARDD (Health Care Access Research and Developmental Disabilities). MAIN MESSAGE: Annual comprehensive health assessments ("health checks") are a recommendation of the 2018 Canadian consensus guidelines for primary care of adults with IDD because of evidence of benefit in this population. Although health checks might require more time to complete for people with IDD than is usual for encounters in primary care, family physicians are in an ideal position to provide this service because of the attributes of family medicine, which include both an orientation to proactive care and the ability to provide continuity of care. Tips and tools are provided for carrying out health checks for adult patients with IDD and for implementing a systematic program of health checks in a group or team practice. CONCLUSION: Health checks can help enhance a family physician's approach to providing care for adults with IDD.
Subject(s)
Developmental Disabilities/therapy , Intellectual Disability/therapy , Physical Examination/methods , Primary Health Care/methods , Adult , Canada , Female , Gynecological Examination/methods , Humans , Middle Aged , Practice Guidelines as TopicABSTRACT
Hypoxia is a state of decreased oxygen reaching the tissues of the body. During prenatal development, the fetus experiences localized occurrences of hypoxia that are essential for proper organogenesis and survival. The response to decreased oxygen availability is primarily regulated by hypoxia-inducible factors (HIFs), a family of transcription factors that modulate the expression of key genes involved in glycolysis, angiogenesis, and erythropoiesis. HIF-1α and HIF-2α, two key isoforms, are important in embryonic development, and likely are involved in lung morphogenesis. We have recently shown that the inducible loss of Hif-1α in lung epithelium starting at E4.5 leads to death within an hour of parturition, with symptoms similar to neonatal respiratory distress syndrome (RDS). In addition to Hif-1α, Hif-2α is also expressed in the developing lung, although the overlapping roles of Hif-1α and Hif-2α in this context are not fully understood. To further investigate the independent role of Hif-2α in lung epithelium and its ability to alter Hif-1α-mediated lung maturation, we generated two additional lung-specific inducible Hif-α knockout models (Hif-2α and Hif-1α+Hif-2α). The intrauterine loss of Hif-2α in the lungs does not lead to decreased viability or observable phenotypic changes in the lung. More interestingly, survivability observed after the loss of both Hif-1α and Hif-2α suggests that the loss of Hif-2α is capable of rescuing the neonatal RDS phenotype seen in Hif-1α-deficient pups. Microarray analyses of lung tissue from these three genotypes identified several factors, such as Scd1, Retlnγ, and Il-1r2, which are differentially regulated by the two HIF-α isoforms. Moreover, network analysis suggests that modulation of hormone-mediated, NF-κB, C/EBPα, and c-MYC signaling are central to HIF-mediated changes in lung development.
Subject(s)
Basic Helix-Loop-Helix Transcription Factors/deficiency , Basic Helix-Loop-Helix Transcription Factors/genetics , Gene Deletion , Hypoxia-Inducible Factor 1, alpha Subunit/deficiency , Phenotype , Respiratory Distress Syndrome, Newborn/genetics , Respiratory Distress Syndrome, Newborn/metabolism , Animals , Animals, Newborn , Gene Regulatory Networks , Genotype , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Lung/metabolism , Lung/pathology , Mice , Respiratory Distress Syndrome, Newborn/pathology , Signal Transduction , Survival Analysis , Transcription, GeneticABSTRACT
Hypoxia inducible factor-1 (HIF1) is a stress-responsive nuclear transcription factor that is activated with a decrease in oxygen availability. HIF1 regulates the expression of genes involved in a cell's adaptation to hypoxic stress, including those with mitochondrial specific function. To gain a more comprehensive understanding of the role of HIF1 in mitochondrial homeostasis, we studied the link between hypoxia, HIF1 transactivation, and electron transport chain (ETC) function. We established immortalized mouse embryonic fibroblasts (MEFs) for HIF1α wild-type (WT) and null cells and tested whether HIF1α regulates mitochondrial respiration by modulating gene expressions of nuclear-encoded ETC components. High-throughput quantitative real-time polymerase chain reaction was performed to screen nuclear-encoded mitochondrial genes related to the ETC to identify those whose regulation was HIF1α-dependent. Our data suggest that HIF1α regulates transcription of cytochrome c oxidase (CcO) heart/muscle isoform 7a1 (Cox7a1) under hypoxia, where it is induced 1.5-2.5-fold, whereas Cox4i2 hypoxic induction was HIF1α-independent. We propose that adaptation to hypoxic stress of CcO as the main cellular oxygen consumer is mediated by induction of hypoxia-sensitive tissue-specific isoforms. We suggest that HIF1 plays a central role in maintaining homeostasis in cellular respiration during hypoxic stress via regulation of CcO activity.
Subject(s)
Electron Transport Complex IV/metabolism , Enzyme Induction , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Mitochondria/metabolism , Oxygen Consumption , Animals , Cell Hypoxia , Cells, Cultured , Clone Cells , Electron Transport Complex IV/antagonists & inhibitors , Electron Transport Complex IV/genetics , Embryo, Mammalian/cytology , Embryo, Mammalian/metabolism , Enzyme Induction/drug effects , Enzyme Inhibitors/pharmacology , Gene Expression Profiling , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Mice , Mice, Transgenic , Mitochondria/drug effects , Mitochondria/enzymology , Oxidative Phosphorylation/drug effects , Oxygen Consumption/drug effects , RNA, Messenger/metabolism , Recombinant Proteins/metabolism , Transcriptional Activation/drug effectsABSTRACT
Wild-type and HIF1α -/- MEF cells were used to determine the role of HIF1α in cadmium-induced toxicity. Cadmium treatment did not affect HIF1-mediated transcription but led to caspase activation and apoptotic cell death in wild-type and HIF1α -/- cells. Cadmium-induced cell death, however, was significantly higher in HIF1α -/- cells as compared to their wild-type counterparts. Increased cell death in the HIF1α -/- cells was correlated with lower metallothionein protein, elevated levels of reactive oxygen species, and decreased superoxide dismutase enzyme activity. The total and oxidized glutathione levels, and, correspondingly, lipid peroxidation levels were elevated in the null cells compared to wild-type cells, indicating increased antioxidant demand and greater oxidative stress. Overall, the results suggest that basal levels of HIF1α play a protective role against cadmium-induced cytotoxicity in mouse embryonic fibroblasts by maintaining metallothionein and antioxidant activity levels.
