Clinical Research Directory

The Genetic Basis of Congenital Heart Disease in Africa

Recent advances in genomic techniques are making possible a new wave of genetic discovery in congenital heart disease (CHD). Existing data suggests that CHD occur in Sub-Saharan Africa at frequencies similar to the rest of the world. In this application, we propose to utilize the unique advantages of Sub-Saharan Africa - a combination of the most genetically diverse populations in the world and of diminished environmental background effects (i.e. low prevalence of smoking, alcohol abuse, obesity in comparison to western countries) - to better understand the genetic basis for congenital heart disease. We will couple next generation genomic techniques with more traditional gene discovery methods to investigate CHD in two African countries: Uganda and Nigeria. The inclusion of syndromic and non-syndromic CHD observed in these populations as well as careful phenotyping (including echocardiography) will greatly enhance our potential to provide insight into the genetic architecture of CHD in African populations. To accomplish this, we plan to enroll families, in whom members have congenital heart malformations consistent with an error of early human development in our research protocol. Patients will be enrolled at the Uganda Heart Institute in Kampala, Uganda, and at the Department of Pediatrics, College of Medicine, University of Lagos, Nigeria, with the potential to include other African sites. High throughput genomic studies will be done at the NIH....

Prevalence and Post-surgical Outcomes of CARdiac Wild-type TransthyrEtin amyloidoSIs in Elderly Patients With Aortic steNosis Referred for Valvular Replacement.

Background: The prevalence of both senile cardiac amyloidosis (CA) and aortic stenosis (AS) markedly increases with age. Aortic stenosis increases left ventricular pressure overload. Cardiac deposits have been observed in AS and the amount of these deposits has been correlated to post-surgical outcome. As they are strong echocardiographic and cardiac MRI imaging similarities between CA and AS, the investigators hypothesized that the deposit observed in AS is transthyretin amyloid deposit. The investigators objective is to demonstrate that amyloid deposit is associated with poor outcomes following aortic stenosis surgical valve replacement. Materiel and methods: 180 patients with indication for surgical aortic valve replacement will be recruited prospectively and consecutively in 5 French centers. A replicative study will be performed in one Austrian center. Echocardiography, cardiac MRI and bone scintigraphy will be performed prior to surgery. During surgery, a basal LV septum biopsy will be collected for determination and quantification of interstitial deposits using specific staining which will be performed in a blind fashion. Clinical outcomes will be recorded during the hospitalization period following the surgery and at 1 year. Alive and re-hospitalization status will be determined. Patients will be classified according to the presence or not of amyloid deposits. Expected results and impact: This study will emphasize how pressure overload stress accelerates and magnifies amyloid deposition usually known to be related to cardiac aging process. It will develop reliable imaging tools and markers to detect cardiac amyloid deposition. Correlation between anatomopathologic analyses and the three different imaging technics will identify accurate imaging markers of CA. A risk stratification model based on amyloid deposits level for the clinical management of these patients will be created combining imaging and biological markers.

Cooperative Assessment of Late Effects for SCD Curative Therapies

Sickle Cell Disease is one of the most common genetic diseases in the United States, occurring in approximately 1 in 400 births. Approximately 100,000 individuals are diagnosed with SCD in the United States. Mortality for children with SCD has decreased substantially over the past 4 decades, with \>99% of those born in high resource settings, including the United States, France, and England, now surviving to 18 years of age. However, the life expectancy of adults with SCD is severely shortened. Dysfunction of the heart, lung, and kidney is directly associated with decreased life expectancy. With the variety of curative therapies that are now available for SCD, long-term health outcomes studies are time-sensitive. As of now, efforts to determine long-term health outcomes following curative therapies for SCD have been limited. Though curative therapies initially should provide a cure for symptoms of SCD, there is the risk of late health outcomes to consider. Defining health outcomes following curative therapy is essential to improve personalized decision-making when considering curative versus disease-modifying therapeutic options. The primary goal of this study is to determine whether curative therapies for individuals with SCD will result in improved or worsening heart, lung, and kidney damage when compared to individuals with SCD receiving standard therapy. The investigators will also explore whether certain genes are associated with a good or bad outcome after curative therapy for SCD.

Promoting Physical Activity and Fitness Among Underserved Latino Families Living in U.S.-Mexico Border Regions

This study has the goal to increase physical activity and fitness among Latinos in San Diego, California and Mexicali, Baja California (U.S.-Mexico border) since these cities have similar diseases such as high rates of heart disease and obesity. Therefore there is a need to have physical activity programs for children and their families. We will collaborate with community centers to have this program available.

Family Genetics Health Education and Healthy Behaviors

Background: \- Family-based approaches to reduce disease risk and promote healthy behaviors may be better than targeting individuals. Risk assessments based on family health history may help educate families on disease risks and encourage them to change physical activity and food choices. Specifically, researchers want to better understand the role of mothers in teaching healthy behaviors to their families. Objectives: * To determine mothers influence on diet and health-related behaviors. * To study an intervention tool that connects family health history and disease risk. Eligibility: \- 18 years of age who have at least one child living at home. Design: * Participants will complete a survey over the phone. The survey will take 30 to 40 minutes to complete. The survey will collect family health history on heart disease, diabetes, colorectal cancer, and breast cancer. * Researchers will give participants a Family Health Package (FHP). The FHP will provide information on family health history and disease risk. It will also recommend behaviors that can reduce health risks. * Two weeks after sending the FHP, participants will complete a phone survey about the FHP materials and their social networks. * Some participants will be invited to focus groups. The focus groups will explore diet and health behavior. They will look at food purchasing and preparation and meal sharing. The groups will also discuss attitudes toward healthy eating and physical activity. Each focus group will last 1 to 2 hours. * Participants will be asked to complete an electronic survey regarding participants health status, causal health beliefs, risk perceptions, and intentions to communicate health information. * Then, participants will have the opportunity to use the electronic version of the FHP, which will assess family health history. * After using the FHeP, participants will complete a short electronic survey to identify knowledge and understanding gained from the use of the application, changes in communication intentions, and suggestions for improvements to the application. * Upon completion of the electronic portion of the study, a study team member will conduct a semi-structured interview to allow the participants to qualitatively evaluate their user experience, including satisfaction and usefulness. * This study process will take approximately 60-90 minutes.

Diagnostic Efficacy of Connected WAtch ECG Versus External Holter ECG

Palpitations are a frequent reason for consultation (16% of total volume) and management in the emergency department. Conventional diagnostic management in our establishment is based on a 48-hour external ECG holter, combined with a stress test if symptoms are triggered by physical activity. The diagnostic difficulty lies in the frequency and duration of this transient symptom. At the time of consultation, the patient is often asymptomatic. The initial strategy is to demonstrate an electrocardiographic trace during the attack, in order to adapt management to the chosen etiology. The HOLTER ECG is the gold standard, but it is not very cost-effective due to the infrequent and random nature of the onset of symptoms. The advent of accessible connected tools such as connected watches seems to be an interesting alternative for acquiring a per-critical trace of symptoms. They are widely adopted by the general population, with ease of use by the individual and long monitoring times. The main aim of the study is to establish the diagnostic cost-effectiveness of one or other of the two diagnostic strategies (rate of identification of the causal arrhythmia) at 6 months from the cardiological consultation.

Healthy Living Anson Study

The goal of this randomized delayed control intervention research study is to see if participants who receive education and healthy prepared meals improve the quality of their diet compared to participants who receive only physical activity education and coaching.

Accuracy of a Cuffless Photoplethysmography (PPG) Chest-Patch Monitor for 24-hour Ambulatory Blood Pressure Monitoring (ABPM)

This study aims to validate the accuracy and reliability of blood pressure (BP) estimates obtained over 24 hours using a PPG-based chest-patch device compared to the gold standard ambulatory blood pressure monitoring (ABPM) method using an upper arm cuff-based oscillometric BP device, in both hypertensive and normotensive individuals referred by their provider to undergo a 24-hours ABPM for clinical indication. The Awake/Asleep test, which is the primary test recommended for automated wearable cuffless BP devices that are cuff-calibrated (based on the 2023 European Society of Hypertension (ESH) recommendations for the validation of cuffless blood pressure measuring devices), will be conducted in this study. The secondary aim of the study is to assess the feasibility and convenience of the PPG-based device.

Personalized Environment and Genes Study

Despite the overwhelming focus on genetic and genomic causes of human disease over the past two decades, it has been estimated that genetics is currently known to explain only 20% and 40% of the etiology of common disease. Thus, it is becoming increasingly apparent that human disease is a consequence of both genetic susceptibility and environmental exposures. Importantly, while individuals cannot change their genetic composition, we do have the ability both personally and as a society, to influence our environment, promoting health and decreasing the risk of disease. The Personalized Environment and Genes Study (PEGS) aims to determine how the environment and gene-environment interactions can inform our understanding of human health and disease. As science has evolved, so too has the science of this project. This evolution was reflected in a change in the title of this project from the Environmental Polymorphisms Registry (EPR) to the Personalized Environment and Genes Study (PEGS) to more accurately reflect the science that can be conducted. PEGS is a unique resource because of the depth of environmental phenotyping which includes extensive information from exposome surveys, as well as whole genome sequencing on a significant number of participants in the cohort. While it is small relative to genomic cohorts, none of these have the extensive environmental data that is present in PEGS. In addition, other cohorts with deep environmental data lack the depth of genomic data that is present in PEGS. Importantly, PEGS has already provided important analytic advances that are of great interest to and can be confirmed in larger cohorts such as All of Us. The Personalized Environment and Genes Study (PEGS) aims to provide a resource for environmental health translational research by examining gene-environment interactions in health and disease. PEGS is an extension of two previous efforts where it began as a pilot study, the Environmental Polymorphisms Study (EPS; IRB# 02E9004) and was approved subsequently as a full protocol titled the Environmental Polymorphisms Registry (EPR) (IRB #04-E-N0053 and transitioned to its current ID# 04-E-0053). The EPR was envisioned as a phenotype-by-genotype registry of participants who had donated DNA samples, and who had agreed to be contacted for follow-up clinical translational studies based on their DNA genotypes. At the time, the only information available was a participant s age, sex, race, and ethnicity. Further phenotyping of a participant and/or any biospecimens obtained were investigated during a follow-up translational clinical study on participants recruited based on their genotype (hence phenotype-by-genotype) and the PEGS was the first recruit-by- genotype study at the NIH. Following a period focused on recruiting approximately 15,000 participants to enable genotyping of rare (approximately 1% minor allele frequency) single nucleotide polymorphisms (SNPs), the PEGS Consortium Project was undertaken in 2010- 2011 to examine, using the DNA of nearly 4,000 participants, approximately 700 SNPs in approximately 80 environmental response genes that work in concert with environmental exposures to elicit a phenotype. Several clinical follow-up studies, genotype-phenotype association studies, and publications have resulted from the PEGS Consortium Project. To expand phenotype information available to researchers, the Health and Exposure Questionnaire was administered between 2013-2014. In 2017, a more detailed Exposome Questionnaire which includes questions relating to the external and internal exposome was administered. This was an important resource through which to integrate exposures with genotype-phenotype association studies. Whole genome sequencing has now been performed on approximately 4700 participants who were reconsented for this purpose, as indicated above. Questionnaire data was fully adjudicated and combined in a robust and searchable database. With the increased power of the data available, the project was renamed as the Personalized Environment and Genes Study (PEGS) and rolled out in Sept. 2021.

Impact of Ketogenic Diets on Cardiovascular Health in Adults With Epilepsy

This research is being done to evaluate the short term and long term effects of ketogenic diets on measures of cardiovascular health. Such measures include cholesterol levels, blood pressure, weight, and thickening of the blood vessel wall over time. Adults aged 18 or older who are already on a ketogenic diet for at least 12 months or who are interested in beginning on the modified Atkins diet may join.

Optimal Settings for Anti Tachycardia Pacing (ATP) on ICD

This is a pragmatic, two-group, cluster randomized trial designed to compare strategies for the Anti Tachycardia Pacing (ATP)-setting in the ventricular tachyarrhythmias (VT) zone when implanting a new implantable cardioverter defibrillator (ICD) in patients with heart disease in hospitals in Denmark. The strategies are: "Burst" or "Ramp" after 1. ATP (which is always burst) in VT zone. VT zone is defined between 180-249 (up to 269 in special cases) heartbeats per minute. The ICD will give either: Burst: The ICD is programmed to give ATP with 4 bursts. Or Ramp: The ICD is programmed to give ATP with 1 burst and 3 ramps. The participating hospitals will be assigned to one of two intervention strategies for periods of 4-months. The given intervention will follow the patient/ICD throughout the life time of the ICD, but with the possibility to reprogram at any time (intention to treat). It is calculated that the study needs a total of 398 events (second to fourth ATP), which is estimated to require 3980 implanted ICDs. The participants will be followed until the end of the ICD life, which is estimated to be around 10 years.

A Study Of Heart Disease Using AI-Enabled Electrocardiography And Focused Cardiac Ultrasound

A study to evaluate feasibility, diagnostic yield, accuracy, and actionable thresholds of POC, immediate-feedback AI-ECG + AI FoCUS screening for cardiac disease in well described community populations.

Non-interventional Study on Guideline Directed Medical Therapy for Patients With Heart Failure (HF) in Germany

Heart failure (HF) is a global public health issue that affects more than 63 million people worldwide. The clinical and economic burden of HF on health care systems is substantial. Heart failure with reduced ejection fraction (HFrEF) represents approximately 50% of the HF patient population.The burden of HF is expected to increase substantially as the population ages, and despite improvements in treatment, hospitalisation and mortality rates remain especially high in HFrEF patients. The current guideline recommendation of directed medical therapy for HFrEF combines four drug classes with proven prognostic benefit: Angiotensin receptor-neprilysin inhibitor (ARNI)/angiotensin converting enzyme inhibitors (ACE I)/angiotensin receptor blockers (ARB), betablockers (BB), mineralocorticoid receptor antagonists (MRA), and sodium-glucose co-transporter 2 inhibitors (SGLT2i). The 2023 ESC (European Society of Cardiology) HF guideline update additionally recommends a rapid in-hospital sequencing approach of guideline-directed medical therapy (GDMT) with frequent physician visits during the first 6 weeks post discharge. Studies investigating the implementation of GDMT in a real-world setting have shown that a significant proportion of patients did not receive the recommended drug combination therapy. Delayed initiation of GDMT contributes to the low number of patients receiving guideline concordant HFrEF therapy, which ultimately may affect patient outcomes. One approach to implement the 2023 ESC guideline updates for heart failure treatment regarding early in-hospital initiation and rapid up-titration of GDMT could be to provide specific training on GDMT recommendations. Such a standardised training is offered to the physicians treating HF patients within selected hospitals of the German Helios hospital network (Helios-GDMT-program). Evidence is needed in order to assess whether in-hospital initiation and up-titration of all phenotype concordant classes of GDMT at hospital discharge can be observed after standardised physician training and whether the GDMT-program implementation also translates into real-world routine outpatient care with respect to use of GDMT and clinical outcomes.

Assessment of Cardiac Function and Anesthesia Depth in Patients Undergoing Cardiac Surgery

The SHAPE study is a prospective, randomized study evaluating changes in cardiac function in adult patients undergoing cardiac surgery with cardiopulmonary bypass. The study focuses on how cardiac function changes during surgery and whether the depth of anesthesia may influence these changes. Participants are randomly assigned to one of two levels of anesthesia depth, guided by the Bispectral Index (BIS). Cardiac function is assessed using transthoracic echocardiography, including myocardial deformation (strain) imaging and myocardial work measurements. Invasive hemodynamic measurements obtained during surgery are also recorded. The primary objective is to assess the change in left ventricular global longitudinal strain (LV GLS) between two intraoperative time points: after induction of anesthesia and before cardiopulmonary bypass, and after separation from cardiopulmonary bypass. The study will also examine whether these changes differ according to the assigned depth of anesthesia and whether echocardiographic and hemodynamic measurements are associated with postoperative outcomes. Participants will also undergo follow-up echocardiographic assessment at 3, 6, and 12 months after surgery to evaluate longer-term changes in cardiac function.

Proteolytic Enzyme Induction Within the Human Myocardial Interstitium

A robust release of endothelin-1-1 (ET) with subsequent ETA subtype receptor (ET-AR) activation occurs in patients following cardiac surgery requiring cardiopulmonary bypass (CPB). Increased ET-AR activation has been identified in patients with poor left ventricular (LV) function (reduced ejection fraction; EF). Accordingly, this study tested the hypothesis that a selective ET-AR antagonist (ET-ARA) administered peri-operatively would favorably affect post-CPB hemodynamic profiles in patients with a pre-existing poor LVEF.

To Evaluate the Long-term Safety and Tolerability of Acoramidis in Participants With Newly Diagnosed ATTR-CM (ACT-EARLY OLE)

The AG10-504 study is an open-label extension study of acoramidis in participants with newly diagnosed transthyretin amyloid cardiomyopathy (ATTR-CM) or both ATTR-CM and transthyretin amyloid polyneuropathy (ATTR-PN).

Reduction or Elimination of Mitral Regurgitation With the SATURN TMVR System (CASSINI-US)

CASSINI-US is a prospective, single-arm, multicenter early feasibility study enrolling up to 15 patients at up to 5 sites in the United States (US). The purpose of the study is to evaluate the technical (implant) feasibility, and safety, and performance of the SATURN TS TMVR System for the treatment of moderate-severe or severe, symptomatic mitral regurgitation through a transcatheter approach. Primary objectives evaluate the implant feasibility, and acute safety and performance of the SATURN TS TMVR System. The secondary objective and additional outcome measures characterize the long-term safety and performance of the SATURN TS TMVR System.

PULSTA TPV Observational Study

The purpose of the study is to determine the long-term follow-up clinical outcomes, effectiveness, and safety data of the PULSTA Transcatheter Pulmonary Valve (TPV) implantation in a real-world situation

Remote ECG Monitoring-Based Phase I Cardiac Rehabilitation After Heart Surgery

This prospective, single-arm study aims to evaluate the effectiveness of Phase I cardiac rehabilitation based on remote electrocardiographic (ECG) monitoring in patients undergoing heart surgery. Eligible participants will receive a comprehensive cardiac rehabilitation program consisting of inpatient and home-based rehabilitation while wearing the MEMO Patch for remote ECG monitoring. Clinical outcomes, including functional exercise capacity, exercise performance, muscle strength, physical function, and health-related quality of life, will be evaluated before rehabilitation, before hospital discharge, and after completion of the rehabilitation program.

A Usability Study of a Multi-channel ECG Monitoring Device

This study it to evaluate the usability of the WearLinq eWave patch in a general adult population.

NYUCI-ES: Psychosocial Intervention to Improve Health Outcomes for Chinese and Korean ADRD Caregivers

This study will conduct a two-arm randomized controlled trial to test the efficacy of a culturally tailored version of the NYU Caregiver Intervention (NYUCI) plus enhanced support (ES) through online chat groups (the NYUCI plus WeChat/Kakaotalk/other social media apps \[popular social media apps for individuals of Chinese or Korean descents\] peer support which we call the NYUCI-ES in reducing health risks for cardiometabolic disease among older Chinese and Korean American adults caring for relatives with ADRD. In collaboration with community organizations across the New York and northern New Jersey metropolitan area, we will enroll 300 caregivers of people with ADRD (150 Chinese and 150 Korean) in this study. Aim 1: Develop culturally adapted informational and educational materials about dementia and caregiving issues for social service providers of the intervention and for family caregivers. Aim 2: Test the hypothesis, H1: A counseling and support intervention (the NYUCI-ES) will significantly improve psychosocial factors such as depression, stress self-rated health and chronic disease management among Chinese and Korean-American ADRD caregivers and these changes will be mediated by improvement in social support. H1a: By the first (6- month) follow-up, the mediators (increases in social support, stress reaction) will improve significantly in the intervention group compared to baseline values and the control group. H1b: These improvements will be maintained, and lead to reduction in depressive symptoms, and improvement in self-reported health and chronic disease self-management by the 12-month follow-up compared to the control group. Aim 3: Test the hypothesis, H2: the NYUCI-ES will reduce biologic risk factors, including metabolic health (glycosylated hemoglobin, BMI) and inflammation (hsCRP, lipid metabolism, etc.) within 6 months of enrollment compared to baseline and a control group; these changes will be mediated through increases in social support and decreases in depressive symptoms and will be maintained at the 12-month follow-up. The public health significance of these findings will likely have an impact on health care policy for CGs from diverse underserved ethnic and cultural backgrounds, potentially reducing morbidity, and improving their quality of life.

Outpatient Rehabilitation Programmes for Myocardial Ischemia, Heart Failure, and COPD: Satisfaction, Participation, Test Outcomes, and Factors Associated With Positive Changes in Test Results as Well as Level of Participation

Aim The aim of this project is to investigate the level of participation, satisfaction, changes in tests, and factors associated with these results in existing rehabilitation programmes at North Zealand Hospital and in the surrounding municipalities among patients with heart diseases and the lung disease chronic obstructive pulmonary disease (COPD). The project is conducted in clinical practice in a non-selected population. Participants Individuals with heart disease and COPD who commence training at North Zealand Hospital. Up to 840 participants may be included over a two-year period. Participants will be recruited at the start of training at North Zealand Hospital. Inclusion criteria: Patients from North Zealand Hospital (Hillerød and Frederikssund) referred with a rehabilitation plan for group-based rehabilitation for heart disease or COPD at North Zealand Hospital Patient consent to participate in the project. There are no exclusion criteria for the project. Intervention Participants will be invited to participate in the project when enrolling in the already existing group-based training programme lasting 6-10 weeks as part of rehabilitation for heart disease and COPD. Data Participation: Number of patients commencing the training period relative to the number of patients referred from the cardiology department Attendance: Number of completed training sessions relative to the total number of possible training sessions during the periods at the hospital and in the municipalities Dropout: Dropout during the hospital-based and municipality-based periods and reasons for dropout The data listed below will, as far as possible, be collected before and after the training period. Physical activity (the final variable) will additionally be measured three months after completion of the municipal programme. 30-second sit-to-stand test\* Six-minute walk test\* Quality of life measured using the CAT questionnaire for COPD and EQ-5D for the two groups of patients with heart disease Musculoskeletal pain measured using a questionnaire with the Numeric Rating Scale for five body regions Physical activity measured using a modified version of the IPAQ questionnaire from the Danish Health and Morbidity Surveys \*These tests are standard and implemented in the existing rehabilitation programmes. Other Data Additional data will include: From questionnaire: educational level and BMI (height and weight) From patient records: age, sex, treatment for heart disease, and extent of other chronic diseases Data from patient records are already collected as part of routine clinical practice independently of this project. Ethics Participants will be invited to the study with written and oral information. Participation will take place after informed consent. The study will be conducted in accordance with the regulations of the Scientific Ethical Committee, to which it will be submitted as soon as possible, and it will be reported in the Capital Region of Denmark's legal system via PRIVACY. The study will be registered in the project database www.clinicaltrials.gov. Data will be stored in the REDCap database system. Dissemination of Results Results will be presented at local and regional meetings and symposia and published in international peer-reviewed scientific journals indexed in PubMed.

Pathways to Prevention Food-is-Medicine Trial

The goal of this study is to learn whether combining healthy food access with personalized tools can help families improve heart health and make lasting lifestyle changes. The main questions the study aims to answer are: * Do the new tools (PRO-CVH and Triple-C) help families improve their heart health? * Which combination of tools and supports works best for families with limited access to healthy food? * Is this type of program easy to carry out and acceptable to families and healthcare teams? Families in the study will include one parent with a BMI greater than 30 who has Medicaid insurance and their child aged 6 to 11 years. Depending on which group they are assigned to, families may: * Receive food and nutrition education via handouts and/or online curriculum * Have access to an online health assessment tool than can help you understand your/your child's risk factors for heart disease * Work with a personalized health coach who can help you set goals for healthier living online/virtually. * Receive medically tailored groceries and cooking classes. Researchers will follow participants for several months to see how their heart health changes and which parts of the program work best together. The information from this study will help design a larger clinical trial to test a practical, cost-effective program that can help families build healthier habits and reduce their risk of heart disease.

Moxie Self-Management and Education Support Program

Health education and self-management support are key facilitators of health behaviours. Moxie is a mixed media, self-management, education and support program for Albertans living with cardiovascular-related chronic conditions. Moxie is built upon our previous work within the ACCESS study (2015-21, n=4761), a RCT that previously tested the Moxie intervention in Alberta. Results demonstrated that MOXIE reduced the rate of hospitalizations (notably for hypertension, angina, hyper/hypoglycemia, heart failure decompensation, and acute kidney complications) by 34% in a population of low-income seniors living with cardiovascular-related chronic conditions. However, before Moxie can be effectively implemented province-wide, another trial is necessary to determine whether benefits can be observed in a larger cohort of patients with cardiovascular-related chronic conditions recruited immediately after hospital discharge (n=9000). Furthermore, the effectiveness of the two components of the ACCESS trial intervention will be assessed individually: (a) The Moxie Program, a tailored health and disease education component developed by a user-experience-centric design process incorporating patients, behavioural scientists, disease specialists, health system administrators and marketing/advertising professionals; and (b) the facilitated relay of clinical information to healthcare providers (letters). The trial is designed as a 2x2 factorial pragmatic, individual-level randomized pragmatic trial of these different interventions. This would yield the following groups: 1. Moxie SMES Program 2. Facilitated Relay 3. Moxie SMES Program and Facilitated Relay 4. True control Self-management education and support (SMES) intervention: This includes weekly physical mailers sent directly to patients' homes throughout the study containing information about chronic conditions, medication use, diet, physical activity, smoking cessation, and self-management/wellness principles. These messages will be refined by the social impact creative design partner and reviewed by clinicians and patients to ensure clinical safety and appropriate tone. Weekly mailers will encourage participants to enroll and consent to participate in the digital program by scanning a QR code or accessing a website where they will sign up for their own personalized Moxie mobile health app, complete a digital consent form and opt-in for electronic delivery of Moxie messages. Facilitated relay intervention: Participants allocated to this intervention will receive letters by mail, one addressed to them, one to their primary care provider, and one to their pharmacist. The letters will not be sent to their primary care provider directly; rather, they will be sent to patients who will be encouraged to take them to their primary care provider and pharmacist should they decide to do so. We hope this will empower patients to start discussions with their healthcare providers. This also supports patient autonomy by enabling patients to decide whether they want to take them to their provider or not. If for whatever reason they do not feel that this is going to be beneficial or of interest, they are not required to do so. The letter would contain a note to the patient's healthcare provider stating that their patient is at-risk of cardiovascular disease and that evidence has shown that the pharmacotherapy is effective in improving outcomes for patients similar to the participant. The primary outcome is readmission for cardiovascular-specific ambulatory care-sensitive conditions (ACSC) based on the most responsible diagnosis listed in CIHI Discharge Abstract Database-(DAD), using established algorithms within 12 months from randomization. This outcome includes all repeat admissions in the study period as recorded in the health record. This outcome is a count variable. We will calculate and compare each intervention arm's mean number and distribution of hospitalizations.