Digital flashcards and medical physiology performance: a dose-dependent effect.

Use of digital flashcards promotes active recall, spaced repetition, and self-assessment academic principles. This work explores the association and dose-dependent effect of this study method and locomotor (LP) and cardiovascular physiology (CP) grades. A single-faculty cohort study of medical LP and CP students was conducted, and 155 and 676 flashcards, respectively, were created through Moodle. An exploratory analysis examined three exam results (2019), and a confirmatory study used a fourth exam (2021) in another CP cohort. Of 685 students enrolled, 558 participated in the exploratory analysis: 319 (69%) for LP and 311 (84%) for CP, of which 203 LP and 267 CP students were flashcard users. Median grades were higher among flashcard users, and the number of cards reviewed was positively correlated with grades (r = 0.275 to 0.388 for LP and r = 0.239 to 0.432 for CP, P < 0.001). Multiple linear regression models confirmed a positive dose-dependent association between results and the number of flashcards studied: for every 100 LP cards reviewed, exam grades increased 0.44-0.75 on a 0-20 scale range (P < 0.001), and for every 1,000 CP flashcards, results raised 0.81-1.08 values (P < 0.05). These findings were confirmed in the 2021 CP cohort of 269 participants, of whom 67% were flashcard users. Digital flashcard revision has a consistent positive dose-dependent association on LP and CP grades.NEW & NOTEWORTHY Implementing flashcard-based strategies is a feasible way to promote active recall, spaced repetition, and self-assessment, and students are highly adherent to these initiatives. There is a positive dose-dependent association between the number of flashcards reviewed and physiology grades. These results are consistent across different physiology subjects, under different cohorts, over short and medium terms.

Clinical relevance of the blanking period on late recurrence after catheter ablation of atrial fibrillation.

INTRODUCTION: Recurrence of atrial fibrillation (AF) within the blanking period after catheter ablation (CA) is traditionally classified as a transient and benign event. However, recent findings suggest that early recurrence (ER) is associated with late recurrence (LR), challenging the predefined "blanking period". We aimed to determine the clinical and procedural predictors of ER and LR after CA and establish the risk of LR in patients who experience ER. METHODS AND RESULTS: Retrospective single-centre study including all patients who underwent a first procedure of AF CA between 2017 and 2019. ER was defined as any recurrence of AF, atrial flutter or atrial tachycardia >30 s within 90 days after CA and LR as any recurrence after 90 days of CA. A total of 399 patients were included, 37% women, median age of 58 years [49-66] and 77% had paroxysmal AF. Median follow-up was 33 months (from 13 to 61). ER after CA was present in 14% of the patients, and LR was reported in 32%. Among patients who experienced ER, 84% also had LR (p < .001). Patients with ER had a higher prevalence of moderate/severe valvular heart disease, persistent AF, previous electrical cardioversion, a larger left atrium, higher coronary artery calcium score, and higher rates of intraprocedural electrical cardioversion and cardiac fibrosis on eletroanatomical mapping compared with patients without ER. After covariate adjustment, ER and female sex were defined as independent predictors of LR (hazard ratio [HR] 4.69; 95% confidence interval [CI], 2.99-7.35; p < .001 and HR 2.73; 95% CI, 1.47-5.10; p = .002, respectively). CONCLUSION: The risk of LR after an index procedure of CA was significantly higher in patients with ER (five-fold increased risk). These results support the imperative need to clarify the clinical role of the blanking period.

Impact of Coronary Artery Calcium Score Screening on Cardiovascular Risk Stratification of Patients with Atrial Fibrillation Undergoing Ablation.

INTRODUCTION: There is a well-established association between atrial fibrillation (AF) and coronary artery disease. Coronary artery calcium score (CACS) is a helpful tool to refine cardiovascular (CV) risk stratification and inform on the best strategies for primary CV prevention. This study aims to evaluate the impact of opportunistic screening with CACS on risk stratification and decision of preventive therapies, in patients with AF. METHODS: Cross-sectional study including patients with AF or atrial flutter undergoing cardiac computed tomography for ablation procedure planning, from 2017 to 2019. Baseline clinical and demographical data were collected. CACS was assessed in patients without coronary artery disease using the Agatston method. RESULTS: A total of 474 patients were included (93% with AF, mean age of 58 ± 10 years, 62% male). CACS >0 was present in 254 (54%) patients. According to CACS and the Society of Cardiovascular Computed Tomography recommendations, 25% of the patients would be candidates for statin therapy and 17% would be candidates for changes in the current statin intensity; in 11 patients (8%), acetylsalicylic acid would be recommended. CONCLUSION: In our study, more than half of the patients undergoing cardiac computed tomography before AF catheter ablation had CACS above zero. Our findings suggest that an opportunistic evaluation of CACS at the time of ablation can be an important tool to improve CV risk stratification, with important clinical and therapeutic implications.

Cardiac rehabilitation in elderly myocardial infarction survivors: focus on circulatory power.

Exercise-based cardiac rehabilitation (EBCR) is paramount after an acute myocardial infarction (AMI). Older individuals have been reported as having a worse prognosis after an AMI, and some series have reported differences in the functional response to EBCR. The peak circulatory power (CP), a non-invasive parameter, has been described as a surrogate for the cardiac power, showing promising results as a comprehensive measure of the cardiovascular response. Whilst this, data concerning the impact of EBCR on CP, particularly among elderly individuals, remains elusive. To address this issue, an observational, retrospective study including all patients admitted due to an AMI who completed a phase II EBCR programme between 11/2012 and 4/2017, was conducted, with CP being analysed by a symptom-limited cardiopulmonary exercise test. A total of 379 patients, 30% aged ≥65 years-old, were included. CP significantly improved after the EBCR programme (in all patients, as well as in both subgroups). Older patients presented lower CP than their younger counterparts at the beginning and the end of the programme, while presenting smaller improvements (122 ± 540 vs 293 ± 638 mmHg mL/kg/min, p = 0.013). This was maintained after adjusting for several potential confounding factors. A contemporary ECBR programme was associated with significant improvements in CP among AMI patients. Though those aged ≥65 years-old presented smaller improvements in CP than younger individuals, these still presented significant increases in this parameter. These results highlight the importance of EBCR in this challenging higher risk group of patients.

Suppression of tumorigenicity 2 after exercise: a systematic review.

Exercise is a pivotal physiological activity, associated with benefits. Whilst the importance of physical activity is consensual along different steps of the cardiovascular (CV) continuum, there has been interest in assessing the CV adaptations to vigorous exercise. Indeed, exercise can be associated with increases in cardiac biomarkers, though the scope of this observation remains elusive. Interleukin 1 receptor related protein, Suppression of tumorigenicity 2 (ST2) is a biomarker related to the pathophysiology of fibrosis, having shown promise in the study of heart failure. Knowledge of ST2 kinetics could improve understanding of the mechanistic pathways related to CV adaptations to exercise. To assess the current state-of-the-art concerning ST2 levels after exercise in healthy individuals. A systematic review was carried out on three databases (Pubmed, ISI Web of Science and Scopus), up to October 2020, using the queries "ST2" or "ST-2" + "exercise" or "running". A total of six studies were included in the review, encompassing 349 subjects (73% male gender) in which ST2 was assessed. Most studies reported increases in ST2 levels after exercise. Three studies, encompassing a total of 219 individuals, described a cut-off level of 35 ng/dL for ST2. In these, 92.7% of subjects had ST2 levels above this cut-off after exercise (running in all studies). Most studies report increased levels of ST2 after exercise, with an important number of individuals exceeding the 35 ng/dL threshold. Given the small number of individuals represented and the lack of imaging data and long-term follow-up, further prospective larger studies should target this.

Enhanced clinical phenotyping by mechanistic bioprofiling in heart failure with preserved ejection fraction: insights from the MEDIA-DHF study (The Metabolic Road to Diastolic Heart Failure).

Background: Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome for which clear evidence of effective therapies is lacking. Understanding which factors determine this heterogeneity may be helped by better phenotyping. An unsupervised statistical approach applied to a large set of biomarkers may identify distinct HFpEF phenotypes.Methods: Relevant proteomic biomarkers were analyzed in 392 HFpEF patients included in Metabolic Road to Diastolic HF (MEDIA-DHF). We performed an unsupervised cluster analysis to define distinct phenotypes. Cluster characteristics were explored with logistic regression. The association between clusters and 1-year cardiovascular (CV) death and/or CV hospitalization was studied using Cox regression.Results: Based on 415 biomarkers, we identified 2 distinct clusters. Clinical variables associated with cluster 2 were diabetes, impaired renal function, loop diuretics and/or betablockers. In addition, 17 biomarkers were higher expressed in cluster 2 vs. 1. Patients in cluster 2 vs. those in 1 experienced higher rates of CV death/CV hospitalization (adj. HR 1.93, 95% CI 1.12-3.32, p = 0.017). Complex-network analyses linked these biomarkers to immune system activation, signal transduction cascades, cell interactions and metabolism.Conclusion: Unsupervised machine-learning algorithms applied to a wide range of biomarkers identified 2 HFpEF clusters with different CV phenotypes and outcomes. The identified pathways may provide a basis for future research.Clinical significanceMore insight is obtained in the mechanisms related to poor outcome in HFpEF patients since it was demonstrated that biomarkers associated with the high-risk cluster were related to the immune system, signal transduction cascades, cell interactions and metabolismBiomarkers (and pathways) identified in this study may help select high-risk HFpEF patients which could be helpful for the inclusion/exclusion of patients in future trials.Our findings may be the basis of investigating therapies specifically targeting these pathways and the potential use of corresponding markers potentially identifying patients with distinct mechanistic bioprofiles most likely to respond to the selected mechanistically targeted therapies.

SGLT-2 Inhibitors in Heart Failure and Type-2 Diabetes: Hitting Two Birds with One Stone?

Type 2 diabetes mellitus (T2DM) and heart failure (HF) have a tremendous impact worldwide, markedly reducing life-expectancy and quality of life. It is now known that each disease represents a risk factor for the other. Moreover, when they are combined, the prognosis is significantly worse. Until recently, these pathologies have been managed independently. However, their treatment paradigm is rapidly changing, with recent cardiovascular outcome trials showing that sodium-glucose cotransporter-2 inhibitors (SGLT-2i) are effective in the management of both diseases. This article explores the interactions between T2DM and HF and the concept of diabetic cardiomyopathy and summarizes recent data regarding the effects of SGLT-2i on HF hospitalization and the proposed pathophysiological mechanisms involved.

Differential Impact of a Cardiac Rehabilitation Program on Functional Parameters in Elderly versus Non-Elderly Myocardial Infarction Survivors.

BACKGROUND: Exercise-based cardiac rehabilitation (EBCR) plays a pivotal role in the management of acute myocardial infarction (AMI). Studies have shown that older individuals have a worse prognosis after an AMI, attesting to the importance of risk reduction strategies. We aimed at assessing the impact of age (patients dichotomized as ≥65 years old or <65 years old) on the functional benefits of an EBCR program among AMI survivors. DESIGN: Observational, retrospective cohort study. PARTICIPANTS: All patients admitted due to an AMI who completed a phase II EBCR program after discharge, between November 2012 and April 2017. INTERVENTION: EBCR program. MEASUREMENTS: Functional parameters were assessed by a symptom-limited cardiopulmonary exercise test. RESULTS: A total of 379 patients were included (30% aged ≥65 years). After the EBCR program, peak oxygen uptake (pVO2) and exercise duration increased significantly. Patients aged ≥65 years presented with more comorbidities and a lower functional capacity. Those aged ≥65 years presented significantly smaller improvements in pVO2 (0.79 ± 2.61 vs. 1.60 ± 3.11 mL/kg/min, p = 0.016) and exercise duration [75 (59-120) vs. 120 s (60-180), p = 0.002]. This was maintained after adjusting for several potential confounders. CONCLUSION: Older patients have a worse functional capacity than their younger counterparts. Still, a contemporary EBCR program was associated with significant functional improvements among those aged ≥65 years. The smaller improvements even after adjustments for potential confounders suggest that physiological differences may contribute to this finding. These results highlight the relevance of EBCR among this higher-risk subgroup.

Sodium-Glucose Co-transporter 2 Inhibitors in the Failing Heart: a Growing Potential.

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new drug class designed to treat patients with type 2 diabetes (T2D). However, cardiovascular outcome trials showed that SGLT2i also offer protection against heart failure (HF)-related events and cardiovascular mortality. These benefits appear to be independent of glycaemic control and have recently been demonstrated in the HF population with reduced ejection fraction (HFrEF), with or without T2D. This comprehensive, evidence-based review focuses on the published studies concerning HF outcomes with SGLT2i, discussing issues that may underlie the different results, along with the impact of these new drugs in clinical practice. The potential translational mechanisms behind SGLT2i cardio-renal benefits and the information that ongoing studies may add to the already existing body of evidence are also reviewed. Finally, we focus on practical management issues regarding SGLT2i use in association with other T2D and HFrEF common pharmacological therapies. Safety considerations are also highlighted. Considering the paradigm shift in T2D management, from a focus on glycaemic control to a broader approach on cardiovascular protection and event reduction, including the potential for wide SGLT2i implementation in HF patients, with or without T2D, we are facing a promising time for major changes in the global management of cardiovascular disease.

A rare case series of mitral valve clefts diagnosed by 3D echocardiography and mini-review of the literature.

Mitral valve cleft is a rare entity. However, it must be recognized as a differential mechanism for mitral valve regurgitation. 3D transesophageal echocardiography plays an essential role in the evaluation of single and multiple mitral valve clefts, improving morphological and functional assessment of the valve, with potential implications on surgical planning. The authors present four rare cases of mitral valve cleft presenting during adulthood, followed by a mini-review about the role of 3D echocardiography, as well as its pitfalls, in the assessment of this complex congenital mitral valve disease.

Three-dimensional proximal flow convergence automatic calculation for determining mitral valve area in rheumatic mitral stenosis.

PURPOSE: Management of patients with mitral stenosis (MS) depends heavily on the accurate quantification of mitral valve area (MVA) using echocardiography. All currently used two-dimensional (2D) methods have limitations. Estimation of MVA using the proximal isovelocity surface area (PISA) method with real time three-dimensional (3D) echocardiography may circumvent those limitations. We aimed to evaluate the accuracy of 3D direct measurement of PISA in the estimation of MVA. METHODS: Twenty-seven consecutive patients (median age of 63 years; 77.8% females) with rheumatic MS were prospectively studied. Transthoracic and transesophageal echocardiography with 2D and 3D acquisitions were performed on the same day. The reference method for MVA quantification was valve planimetry after 3D-volume multiplanar reconstruction. A semi-automated software was used to calculate the 3D flow convergence volume. RESULTS: Compared to MVA estimation using 3D planimetry, 3D PISA showed the best correlation (rho=0.78, P<.0001), followed by pressure half-time (PHT: rho=0.66, P<.001), continuity equation (CE: rho=0.61, P=.003), and 2D PISA (rho=0.26, P=.203). Bland-Altman analysis revealed a good agreement for MVA estimation with 3D PISA (mean difference -0.03 cm2 ; limits of agreement (LOA) -0.40-0.35), in contrast to wider LOA for 2D methods: CE (mean difference 0.02 cm2 , LOA -0.56-0.60); PHT (mean difference 0.31 cm2 , LOA -0.32-0.95); 2D PISA (mean difference -0.03 cm2 , LOA -0.92-0.86). CONCLUSIONS: MVA estimation using 3D PISA was feasible and more accurate than 2D methods. Its introduction in daily clinical practice seems possible and may overcome technical limitations of 2D methods.

Diastolic dysfunction in the diabetic continuum: association with insulin resistance, metabolic syndrome and type 2 diabetes.

BACKGROUND: Diabetes increases the risk of heart failure but the underlying mechanisms leading to diabetic cardiomyopathy are poorly understood. Left ventricle diastolic dysfunction (LVDD) is one of the earliest cardiac changes in these patients. We aimed to evaluate the association between LVDD with insulin resistance, metabolic syndrome (MS) and diabetes, across the diabetic continuum. METHODS: Within a population-based study (EPIPorto), a total of 1063 individuals aged ≥45 years (38% male, 61.2 ± 9.6 years) were evaluated. Diastolic function was assessed by echocardiography, using tissue Doppler analysis (E' velocity and E/E' ratio) according to the latest consensus guidelines. Insulin resistance was assessed using the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) score. RESULTS: The HOMA-IR score correlated to E' velocity (ρ = -0.20;p < 0.0001) and E/E' ratio (ρ = 0.20; p < 0.0001). There was a progressive worsening in E' velocity (p for trend < 0.001) and in E/E' ratio across HOMA-IR quartiles (p for trend <0.001). Individuals in the highest HOMA-IR quartile were more likely to have LVDD, even after adjustment for age, sex, blood pressure and body mass index (adjusted OR: 1.82; 95% CI: 1.09-3.03). From individuals with no MS, to patients with MS and no diabetes, to patients with diabetes, there was a progressive decrease in E' velocity (11.2 ± 3.3 vs 9.7 ± 3.1 vs 9.2 ± 2.8 cm/s; p < 0.0001), higher E/E' (6.9 ± 2.3 vs 7.8 ± 2.7 vs 9.0 ± 3.6; p < 0.0001) and more diastolic dysfunction (adjusted OR: 1.62; 95% CI: 1.12-2.36 and 1.78; 95% CI: 1.09-2.91, respectively). CONCLUSIONS: HOMA-IR score and metabolic syndrome were independently associated with LVDD. Changes in diastolic function are already present before the onset of diabetes, being mainly associated with the state of insulin resistance.

HIV patients have impaired diastolic function that is not aggravated by anti-retroviral treatment.

PURPOSE: Recent studies have shown that HIV infection is independently associated with heart failure. Diastolic dysfunction (DD) is frequent in HIV patients, but it is unclear whether this is an effect of the HIV infection itself or of the anti-retroviral therapy (ART). Our aim was to compare diastolic function in HIV treatment-naïve, HIV-ART patients and controls. METHODS: We prospectively enrolled 206 consecutive patients with HIV-1 infection and 30 controls, selected by frequency matching for age and sex. HIV patients were divided in two subgroups: ART-naïve (n = 88) and ART (n = 118). Diastolic function was assessed and graded by echocardiography, according to modern consensus criteria and using tissue Doppler analysis. RESULTS: Compared to controls, ART-naïve patients had lower E' velocities (E' septal: 10.2 ± 2.4 vs 11.9 ± 2.6 cm/s, p = 0.02), higher E/E' ratio (7.8 ± 1.9 vs 6.9 ± 1.6,p = 0.02) and higher prevalence of DD (19 % vs 3.3 %,p = 0.05). HIV patients under ART also had worse diastolic function compared to controls (E' septal: 10.3 ± 2.5 cm/s;p < 0.01; E/E'ratio: 8.0 ± 2.0,p < 0.01; DD prevalence: 23 %;p = 0.01), but no significant differences were found between ART-naïve and ART HIV subgroups. In multivariable logistic regression analysis, age and body mass index were the only independent predictors of reduced diastolic reserve in HIV patients. Regarding systolic function, there were no significant differences in ejection fraction or S' velocities between controls and HIV subgroups. CONCLUSIONS: HIV treatment-naïve patients have reduced diastolic reserve that is not worsened by ART. These data reinforce the association of diastolic dysfunction with the HIV infection itself and not with the anti-retroviral therapy.

METformin in DIastolic Dysfunction of MEtabolic syndrome (MET-DIME) trial: rationale and study design : MET-DIME trial.

PURPOSE: Insulin resistance plays a central role in the pathophysiology of metabolic syndrome (MS). Its cardiac deleterious effects are characterized by an increase in fibrous tissue that increases myocardial stiffness and contributes to subclinical left ventricular diastolic dysfunction (LVDD) and heart failure with preserved ejection fraction in patients with MS. In addition to lifestyle counseling (LC), metformin treatment may attenuate or even reverse diastolic dysfunction in these patients. This trial aims to evaluate if treating non-diabetic patients with MS and LVDD with metformin in addition to LC improves diastolic function and assess its impact in functional capacity and health-related quality of life (HRQoL). DESIGN: MET-DIME is a phase II prospective, randomized, open-label, blinded-endpoint trial with a scheduled follow-up of 24 months. Fifty-four patients (adults 40-65 years old with AHA/NHLBI criteria of MS and rest LVDD) will be randomized by minimization to LC only or LC plus metformin (target dose of 1,000 mg twice daily). The primary endpoint will be change in mean of early diastolic mitral annular velocity, an echocardiographic parameter highly correlated with myocardial fibrosis (serial measurements will be performed at 6, 12 and 24 months). The secondary endpoints will include change in diastolic parameters at rest; metabolic, inflammatory and remodeling biomarkers; functional capacity; adipose tissue volumes and HRQoL. CONCLUSION: MET-DIME is a pragmatic trial designed to evaluate if adding metformin to the standard treatment of patients with MS improves diastolic dysfunction, assessing its impact in metabolic homeostasis, proinflammatory state, functional capacity and HRQoL.

Digital health and cardiovascular healthcare professionals in Portugal: Current status, expectations and barriers to implementation.

INTRODUCTION AND OBJECTIVES: Digital health (DH) is a broad concept, bringing together technology and healthcare, that is playing an increasingly important role in the daily routine of healthcare professionals (HCPs) and promises to contribute to the prevention and treatment of cardiovascular disease. There are no solid data on the position of Portuguese HCPs toward the implementation of DH in cardiovascular medicine. This national cross-sectional study aims to provide a snapshot of DH implementation in Portuguese cardiovascular HCP routines and to identify both expectations and barriers to its adoption. METHODS: An 18-question survey was created specifically for this study and distributed to 1174 individuals on the Portuguese Society of Cardiology mailing list. RESULTS: We collected 117 valid responses (response rate 10%). Almost all participants had smartphones and laptops, and two-thirds had tablets. Electronic medical information systems were the most used DH tool (84% of respondents) and were considered the most important for improving cardiovascular care. Implantable technologies (sensors and devices), telemedicine and social media were used by more than two out of three respondents and considered «very important¼ or «extremely important¼ by most of them. Most participants showed positive expectations regarding the impact of DH in cardiovascular medicine: 78% agreed that DH could improve health outcomes, 64% that it promotes health literacy and 63% that it could decrease healthcare costs. The top-rated barriers were patients' inability to use smartphones, limited access to electronic devices, and lack of legal regulation of DH. CONCLUSION: Most Portuguese cardiovascular HCPs had at least three electronic devices (mainly smartphones, laptops and tablets) and showed positive expectations regarding DH's current and future impact on cardiovascular medicine. Patient DH literacy, technology adoption, and DH regulation were identified as the most important barriers to increasing the adoption of DH tools in cardiovascular medicine.