Clinical Phenotypes in Patients With Type 2 Diabetes Mellitus: Characteristics, Cardiovascular Outcomes and Treatment Strategies.

PURPOSE OF REVIEW: With recent advances in the pharmacological management of type 2 diabetes mellitus (T2DM), there is a growing need to understand which patients optimally benefit from these novel therapies. Various clinical clustering methodologies have emerged that utilise data-agnostic strategies to categorise patients that have similar clinical characteristics and outcomes; broadly, this characterisation is termed phenotyping. In patients with T2DM, we aimed to describe patient characteristics from phenotype studies, their cardiovascular risk profiles and the impact of antihyperglycemic treatment. RECENT FINDINGS: Numerous phenotypic studies have been undertaken that have utilised a combination of clinical, biochemical, imaging and genetic variables. Each of these has produced phenotypes that display a spectrum of cardiovascular risk. Studies that aimed to describe pathophysiological phenotypes generally identified five phenotypes: autoimmune phenotype, insulin-related phenotypes (including permutations of insulin deficiency and resistance), obesity phenotype, ageing phenotype, and a sex-related phenotype. Studies examining risk profiles have demonstrated that across such phenotypes there is a spectrum of risk for diabetic complications. Few studies have examined treatment effects across these phenotypes, and thus provide little insights towards making phenotype-guided treatment decisions Clustering analyses in patients with T2DM have identified distinct phenotypes with unique risk profiles. Further studies are needed that harness the use of clinical, biochemical, imaging and genetic data to explore therapeutic heterogeneity and response to antihyperglycemic treatment across the spectrum of patient phenotypes.

The Canadian Women's Heart Health Alliance ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women - Chapter 9: Summary of Current Status, Challenges, Opportunities, and Recommendations.

This final chapter of the Canadian Women's Heart Health Alliance "ATLAS on the Epidemiology, Diagnosis, and Management of Cardiovascular Disease in Women" presents ATLAS highlights from the perspective of current status, challenges, and opportunities in cardiovascular care for women. We conclude with 12 specific recommendations for actionable next steps to further the existing progress that has been made in addressing these knowledge gaps by tackling the remaining outstanding disparities in women's cardiovascular care, with the goal to improve outcomes for women in Canada.

Dans ce chapitre final de l'ATLAS sur l'épidémiologie, le diagnostic et la prise en charge de la maladie cardiovasculaire chez les femmes de l'Alliance canadienne de santé cardiaque pour les femmes, nous présentons les points saillants de l'ATLAS au sujet de l'état actuel des soins cardiovasculaires offerts aux femmes, ainsi que des défis et des occasions dans ce domaine. Nous concluons par 12 recommandations concrètes sur les prochaines étapes à entreprendre pour donner suite aux progrès déjà réalisés afin de combler les lacunes dans les connaissances, en s'attaquant aux disparités qui subsistent dans les soins cardiovasculaires prodigués aux femmes, dans le but d'améliorer les résultats de santé des femmes au Canada.

Use of Digital Health Technology in Heart Failure and Diabetes: a Scoping Review.

Use of digital health technologies (DHT) in chronic disease management is rising. We aim to evaluate the impact of DHT on clinical outcomes from randomized controlled trials (RCTs) of patients with heart failure (HF) and diabetes mellitus (DM). Electronic databases were searched for DHT RCTs in patients with HF and DM until February 2021. Patient characteristics and outcomes were analyzed. One published (N = 519) and 6 registered (N = 3423) eligible studies were identified, with one study exclusively including HF and DM patients. Median DHT monitoring was 12 months, with six studies using mobile platforms as their key exposure. Clinical outcomes included quality-of-life or self-care surveys (n = 1 each), physical activity metrics, changes in biomarkers, and other clinical endpoints (n = 3). Limited data exist on RCTs evaluating DHT in patients with concomitant HF and DM. Further work should define standardized clinical endpoints and platforms that can manage patients with multiple comorbidities.

Postimplant Phosphodiesterase-5 Inhibitor Use in Centrifugal Flow Left Ventricular Assist Devices.

OBJECTIVES: This study examined the association between phosphodiesterase-5 inhibitor (PDE-5i) use and outcomes in patients with contemporary centrifugal flow left ventricular assist devices (LVADs). BACKGROUND: PDE-5i use may affect outcomes in patients with continuous flow LVADs. METHODS: Patients enrolled in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support), with HeartMate 3 (n = 4,628) or HeartWare Ventricular Assist Device (HVAD) (n = 2,601) implant were included in the analysis. The mean duration of follow-up was 11.94 ± 8.65 months. PDE-5is were used in 2,173 patients. The primary endpoint was the composite of all-cause mortality, ischemic stroke, and pump thrombosis. Propensity matching and stabilized inverse probability of treatment weights were used to adjust for baseline differences between patients receiving and not receiving PDE-5i. Adjusted Cox proportional hazards analysis was performed for each outcome. RESULTS: The primary endpoint was lower in the PDE-5i group (adjusted HR: 0.77; 95% CI: 0.69-0.86; P < 0.0001; HeartMate 3: adjusted HR: 0.77; 95% CI: 0.64-0.92; P = 0.0044; HVAD: adjusted HR: 0.76; 95% CI: 0.66-0.88; P = 0.0002). All-cause mortality was lower with PDE-5is (adjusted HR: 0.75; 95% CI: 0.65-0.86; P < 0.0001; HeartMate 3: adjusted HR: 0.70; 95% CI: 0.57-0.86; P = 0.0007; HVAD: adjusted HR: 0.78; 95% CI: 0.65-0.94; P = 0.0098) and fewer ischemic strokes with PDE-5is were observed (adjusted HR: 0.71; 95% CI: 0.56-0.89; P = 0.003; HeartMate 3: adjusted HR: 0.67; 95% CI: 0.45-0.99; P = 0.045; HVAD: adjusted HR: 0.73; 95% CI: 0.56-0.97; P = 0.03). LVAD thrombosis was unchanged with PDE-5is, with overall low event rates observed. CONCLUSIONS: Postimplant PDE-5i use was associated with lower mortality and ischemic strokes in patients with centrifugal flow LVADs.

Clinical Prediction Models for Heart Failure Hospitalization in Type 2 Diabetes: A Systematic Review and Meta-Analysis.

Background Clinical prediction models have been developed for hospitalization for heart failure in type 2 diabetes. However, a systematic evaluation of these models' performance, applicability, and clinical impact is absent. Methods and Results We searched Embase, MEDLINE, Web of Science, Google Scholar, and Tufts' clinical prediction registry through February 2021. Studies needed to report the development, validation, clinical impact, or update of a prediction model for hospitalization for heart failure in type 2 diabetes with measures of model performance and sufficient information for clinical use. Model assessment was done with the Prediction Model Risk of Bias Assessment Tool, and meta-analyses of model discrimination were performed. We included 15 model development and 3 external validation studies with data from 999 167 people with type 2 diabetes. Of the 15 models, 6 had undergone external validation and only 1 had low concern for risk of bias and applicability (Risk Equations for Complications of Type 2 Diabetes). Seven models were presented in a clinically useful manner (eg, risk score, online calculator) and 2 models were classified as the most suitable for clinical use based on study design, external validity, and point-of-care usability. These were Risk Equations for Complications of Type 2 Diabetes (meta-analyzed c-statistic, 0.76) and the Thrombolysis in Myocardial Infarction Risk Score for Heart Failure in Diabetes (meta-analyzed c-statistic, 0.78), which was the simplest model with only 5 variables. No studies reported clinical impact. Conclusions Most prediction models for hospitalization for heart failure in patients with type 2 diabetes have potential concerns with risk of bias or applicability, and uncertain external validity and clinical impact. Future research is needed to address these knowledge gaps.

How Diabetes and Heart Failure Modulate Each Other and Condition Management.

Heart failure (HF) and diabetes mellitus (DM) confer considerable burden on the health care system. Although these often occur together, DM can increase risk of HF, whereas HF can accelerate complications of DM. HF is a clinical syndrome resulting from systolic or diastolic impairment caused by ischemic, nonischemic (eg, DM), or other etiologies. HF exists along a spectrum from stage A (ie, persons at risk of DM) to stage D (ie, refractory HF from end-stage DM cardiomyopathy [DMCM]). HF is further categorized by reduced, midrange, and preserved ejection fraction (EF). In type 2 DM, the most prevalent form of DM, several pathophysiological mechanisms (eg, insulin resistance and hyperglycemia) can contribute to myocardial damage, leading to DMCM. Management of HF and DM and patient outcomes are guided by EF and drug efficacy. In this review, we focus on the interplay between HF and DM on disease pathophysiology, management, and patient outcomes. Specifically, we highlight the role of novel antihyperglycemic (eg, sodium glucose cotransporter 2 inhibitors) and HF therapies (eg, renin-angiotensin-aldosterone system inhibitors) on HF outcomes in patients with DM and HF.

Feasibility of Incorporating Voice Technology and Virtual Assistants in Cardiovascular Care and Clinical Trials.

PURPOSE OF REVIEW: With the rising cost of cardiovascular clinical trials, there is interest in determining whether new technologies can increase cost effectiveness. This review focuses on current and potential uses of voice-based technologies, including virtual assistants, in cardiovascular clinical trials. RECENT FINDINGS: Numerous potential uses for voice-based technologies have begun to emerge within cardiovascular medicine. Voice biomarkers, subtle changes in speech parameters, have emerged as a potential tool to diagnose and monitor many cardiovascular conditions, including heart failure, coronary artery disease, and pulmonary hypertension. With the increasing use of virtual assistants, numerous pilot studies have examined whether these devices can supplement initiatives to promote transitional care, physical activity, smoking cessation, and medication adherence with promising initial results. Additionally, these devices have demonstrated the ability to streamline data collection by administering questionnaires accurately and reliably. With the use of these technologies, there are several challenges that must be addressed before wider implementation including respecting patient privacy, maintaining regulatory standards, acceptance by patients and healthcare providers, determining the validity of voice-based biomarkers and endpoints, and increased accessibility. SUMMARY: Voice technology represents a novel and promising tool for cardiovascular clinical trials; however, research is still required to understand how it can be best harnessed.

A Pragmatic Approach to Weaning Temporary Mechanical Circulatory Support: A State-of-the-Art Review.

Temporary mechanical circulatory support (TMCS) provides short-term support to patients with or at risk of refractory cardiogenic shock. Although indications, contraindications, and complications of TMCS may guide device selection, optimal strategies for device weaning and explant remain poorly defined. Under the revised adult heart allocation policy implemented by the United Nations for Organ Sharing in October 2018, rejustification of heart transplant listing status includes demonstrating TMCS dependency with attempted device wean trials. However, standardized device-specific weaning and explant protocols have not been proposed or evaluated. This review highlights when to use percutaneous TMCS in cardiogenic shock, with a focus on weaning and explant considerations. Terminology for important concepts that guide device escalation, de-escalation, and explantation have been defined. Clinical, hemodynamic, metabolic, and imaging features have been defined, which can guide a tailored approach to TMCS weaning and explant based on the approach used at the Cleveland Clinic. A narrative review of published studies that have reported TMCS weaning protocols and survey results of member centers from CS-MCS working group centers is also provided. Future research is needed to better understand optimal timing and implementation of standardized protocols to achieve successful TMCS weaning and explant.

Use of Actigraphy (Wearable Digital Sensors to Monitor Activity) in Heart Failure Randomized Clinical Trials: A Scoping Review.

BACKGROUND: Actigraphy-based measurements of physiologic parameters may enable design of patient-centric heart failure (HF) clinical trials. Recently, the Heart Failure Collaboratory focused on recommendations for meaningful change and use of actigraphy as an end point in HF clinical trials. We aimed to evaluate randomized controlled trials (RCTs) that have quantified the impact of HF interventions using actigraphy. METHODS: Using a scoping review strategy, we evaluated the use of actigraphy in HF RCTs. Studies were identified through electronic searches of Embase, OVID Medline, PubMed, and Cochrane Review. Data on trial characteristics and results were collected. RESULTS: We identified 11 RCTs with a total of 1,455 participants. The risk of bias across the included trials was high overall. All trials had the primary outcomes reflecting measures of either physical activity (n = 8), sleep (n = 2), or both (n = 1). Five trials evaluated response to pharmacologic therapies compared with placebo, 3 evaluated physical activity interventions, 2 evaluated group or cognitive therapy, and 1 evaluated sleep-ventilation strategy. Sample sizes ranged from 30 to 619 participants. There was significant heterogeneity relating to device type, body placement site, and handling of missing actigraphy data. Duration of monitoring ranged from 48 hours to 12 weeks. None of the studies evaluating pharmacologic therapies (n = 5) demonstrated a significant improvement of actigraphy-based primary end point measurements. CONCLUSIONS: There is significant heterogeneity in the use, methodology, and results of actigraphy-based HF RCTs. Our results highlight the need to develop, standardize, and validate actigraphy-specific outcomes for use in HF clinical trials.

Sex, Race, and Age Differences of Cardiovascular Outcomes in Cardiac Resynchronization Therapy RCTs: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiac resynchronization therapy (CRT) is beneficial in patients who have heart failure with reduced ejection fraction or arrhythmic events. However, most randomized controlled trials (RCTs) showing survival benefits primarily enrolled older white men. This study aims to evaluate CRT efficacy by sex, race, and age in RCTs. METHODS: Five electronic databases (CINAHL, Embase, Emcare, Medline, and PubMed) were searched from inception to July 12, 2021 for RCTs with CRT in adult patients. Data were analyzed for clinical outcomes including all-cause or cardiovascular (CV) death, worsening heart failure (HF), and HF hospitalization (HFH) according to sex, race, and age. RESULTS: Among six RCTs with up to moderate risk of bias, 54% (n = 3,630 of 6,682; mean age 64 years, 22% female, 8% black patients) had CRT device implantation. All-cause death (odds ratio [OR], 0.51; P = 0.053) was reduced in female versus male CRT patients, whereas CV death, HFH, or all-cause death with worsening HF or HFH did not differ significantly. No difference was seen in CRT patients for all-cause death and worsening HF (OR, 1.32; P = 0.46) among white vs black patients or for all-cause death and HFH (OR, 1.19; P = 0.55) among ≥ 65 versus < 65 years. CONCLUSIONS: Whereas all-cause death was lower in female CRT patients, other reported outcomes did not significantly differ by sex, race, or age. Only 6 studies partially reported outcomes. Thus, enhanced reporting and analyses are required to overcome such paucity of data to evaluate the impact of these factors on clinical outcomes in distinct patient cohorts with CRT indication.

CONTEXTE: La thérapie de resynchronisation cardiaque (TRC) est salutaire chez les patients qui souffrent d'insuffisance cardiaque avec fraction d'éjection réduite ou qui subissent des épisodes arythmiques. Toutefois, la plupart des essais contrôlés randomisés (ECR) montrant des bienfaits en matière de survie ont été principalement menés chez des hommes blancs âgés. Cette étude vise à évaluer l'efficacité de la TRC en fonction du sexe, de la race et de l'âge des participants aux ECR. MÉTHODOLOGIE: Nous avons effectué des recherches dans cinq bases de données électroniques (CINAHL, Embase, Emcare, Medline et PubMed) en ciblant une période allant de la date de leur création jusqu'au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant subi une TRC. Les données ont fait l'objet d'une analyse axée sur les résultats cliniques, notamment les décès toutes causes confondues ou d'origine cardiovasculaire (CV), l'aggravation de l'insuffisance cardiaque (IC) et les hospitalisations pour cause d'IC (HIC), en fonction du sexe, de la race et de l'âge des patients. RÉSULTATS: Dans six ECR présentant un risque de biais tout au plus modéré, 54 % des patients (n = 3 630 sur 6 682; âge moyen : 64 ans, 22 % de femmes, 8 % de patients noirs) étaient porteurs d'un dispositif de RC. Les décès toutes causes confondues (rapport de cotes [RC] : 0,51; p = 0,053) étaient moins nombreux chez les femmes que chez les hommes parmi les patients ayant subi une TRC. En revanche, aucune différence significative entre les deux sexes n'a été relevée en ce qui concerne les décès d'origine CV, les HIC ou les décès toutes causes confondues liés à l'aggravation de l'IC ou aux HIC. Au sein de la population ayant subi une TRC, aucune différence n'a été observée quant aux décès toutes causes confondues et à l'aggravation de l'IC (RC : 1,32; p = 0,46) chez les patients blancs par rapport aux patients noirs. Il y avait aussi absence de différence quant aux décès toutes causes confondues et aux HIC (RC : 1,19; p = 0,55) chez les patients âgés de 65 ans ou plus par rapport aux patients âgés de moins de 65 ans au sein de la même population. CONCLUSIONS: Les décès toutes causes confondues étaient moins nombreux chez les femmes qui avaient subi une TRC, mais les autres résultats rapportés ne différaient pas significativement selon le sexe, la race ou l'âge des patients. Seulement six études ont signalé partiellement les résultats. Des rapports et des analyses plus détaillés sont nécessaires pour remédier à la paucité des données et ainsi permettre d'évaluer l'effet des facteurs étudiés sur les résultats cliniques au sein de cohortes distinctes de patients chez qui la TRC est indiquée.

Sex, Race, and Age Differences in Cardiovascular Outcomes in Implantable Cardioverter-Defibrillator Randomized Controlled Trials: A Systematic Review and Meta-analysis.

BACKGROUND: Data are limited regarding the use of implantable cardioverter-defibrillators (ICDs) in diverse populations. This study explores cardiovascular (CV) outcomes and mortality from ICD randomized controlled trials (RCTs), by sex, race, and age. METHODS: Five electronic databases (PubMed, Emcare, Embase, MEDLINE, and Cumulative Index to Nursing & Allied Health Literature CINAHL) were searched for dates from their inception to July 12, 2021, for RCTs of ICD therapy in adult patients. Data were analyzed for clinical outcomes, including all-cause or CV death, and heart failure hospitalization (HFH). RESULTS: Among 5 RCTs (mean age: 63 years; 78% male; 76% White) with moderate overall risk of bias, clinical outcomes in patients with an ICD (n = 3260) vs a control group (n = 3685) were compared. No between-group sex differences were observed for all-cause death (odds ratio [OR] 0.86, P = 0.51), CV death (OR 0.98, P = 0.96), HFH (OR 0.95, P = 0.87), or HFH and all-cause death (OR 0.83, P = 0.51) in the ICD group, in a comparison of male vs female sex. All-cause death (OR 1.20, P = 0.67) did not differ for White vs Black patients receiving ICD therapy. Outcomes data for other non-White, non-Black race groups were often unreported. Most RCTs originated in North America, had male leadership, and were evenly sponsored by industry vs peer-reviewed funding. CONCLUSIONS: Outcomes data are sparse, by sex, race, and age, in current RCTs evaluating ICD therapy. Although ICD patient outcomes did not significantly differ by sex or race, improved data analyses and reporting are needed to determine the relationship between these sociocultural factors and clinical outcomes among distinct ICD patient cohorts.

CONTEXTE: Les données sur l'utilisation des défibrillateurs cardioverteurs implantables (DCI) dans diverses populations sont limitées. Cette étude porte sur les résultats cardiovasculaires (CV) et les décès liés aux DCI qui ont été signalés dans le cadre d'essais contrôlés randomisés (ECR), en fonction du sexe, de la race et de l'âge. MÉTHODOLOGIE: Des recherches ont été effectuées dans cinq bases de données électroniques (PubMed, EmCare, Embase, Medline et CINAHL [Cumulative Index to Nursing & Allied Health Literature]) en ciblant une période allant de la date de leur création jusqu'au 12 juillet 2021 afin de recenser les ECR menés chez des patients adultes ayant reçu un DCI. Les données ont été analysées en fonction des résultats cliniques, notamment les décès toutes causes confondues ou d'origine CV et les hospitalisations pour insuffisance cardiaque (hIC). RÉSULTATS: Cinq ECR (âge moyen des patients : 63 ans; 78 % d'hommes; 76 % de race blanche) présentant globalement un risque de biais modéré ont permis de comparer les résultats cliniques obtenus chez les patients ayant reçu un DCI (n = 3 260) et ceux du groupe témoin (n = 3 685). Aucune différence intergroupe entre les sexes n'a été observée pour les décès toutes causes confondues (rapport de cotes [RC] : 0,86, p = 0,51), les décès d'origine CV (RC : 0,98, p = 0,96) et les hIC (RC : 0,95, p = 0,87), ou les hIC et les décès toutes causes confondues (RC : 0,83, p = 0,51) au sein du groupe de patients ayant reçu un DCI, dans une comparaison entre les sexes. Aucune différence entre les patients de race blanche et de race noire ayant reçu un DCI n'a été notée pour ce qui est des décès toutes causes confondues (RC : 1,20, p = 0,67). Souvent, les données sur les résultats obtenus au sein de groupes de patients de race autre que blanche ou noire n'étaient pas signalées. La plupart des ECR avaient été menés en Amérique du Nord, étaient dirigés par des hommes et commandités à parts égales par l'industrie et des organismes offrant du financement approuvé par les pairs. CONCLUSIONS: Les ECR portant sur l'utilisation des DCI fournissent actuellement peu de données sur les résultats en fonction du sexe, de la race et de l'âge. Les résultats obtenus chez les patients ayant reçu un DCI ne différaient pas significativement selon le sexe ou la race. Néanmoins, des analyses de données et des rapports plus détaillés sont nécessaires pour déterminer la relation entre ces facteurs socioculturels et les résultats cliniques au sein de cohortes distinctes de patients ayant reçu un DCI.

Impella RP as a bridge to cardiac transplant for refractory late right ventricular failure in setting of left ventricular assist device.

Right ventricular (RV) failure remains a major complication after surgical implantation of a left ventricular assist device (LVAD). While the use of a percutaneous RV assist device has been described as a short-term bridge to recovery in end-stage heart failure patients with early post-operative RV failure after index LVAD implant, management of refractory late RV failure remains challenging in these patients. We report the first successful case of extended Impella RP use as a safe and effective bridge to orthotopic heart transplant in an LVAD patient with refractory, haemodynamically significant late RV failure. The Impella RP provided support for 37 days. Haemodynamically intolerant arrhythmia precluded use of inotropic support. No adverse complications related to percutaneous Impella RP support were seen. We also review potential considerations for mechanical circulatory support strategies in this setting: central RV assist device cannulation requires sternotomy incision that can impact subsequent cardiac surgeries, while percutaneous Protek Duo insertion requires adequate vessel size and patency. With an LVAD in situ, veno-arterial extracorporeal membrane oxygenation was not considered for isolated RV support in this case. The patient is currently over 6 months post-orthotopic heart transplant.