Key Points:

• Despite prior data suggesting decrease in metabolic stress may reduce atrial fibrillation (AF) progression, the effects of aggressive lifestyle and risk factor modifications (LRFM) or metformin on AF progression remain unknown.
• In this prospective, randomized, open-label clinical trial, 149 patients with atrial fibrillation and an implanted cardiac device capable of continuous AF monitoring were randomized to standard of care, metformin, LRFM or metformin + LRFM.
• Metformin, LRFM, or the combination did not reduce AF burden compared to standard of care although both LRFM arms reduced AF symptom scores.

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Key Points

• Patients with heart failure with preserved ejection fraction (HFpEF) and obesity often have significant functional limitations.
• The SUMMIT trial demonstrated that tirzepatide (TZP), a dual GIP/GLP-1 receptor agonist, improved clinical outcomes, reduced symptom burden, and enhanced functional status in patients with HFpEF and obesity.
• These benefits were likely driven by reductions in cardiac filling pressures, volume overload, and heart failure medication requirements.

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KEY POINTS:

• Hierarchical analysis prioritizing significant events more effectively traditional composite outcomes, offering clearer clinical guidance
• In a pre-specified analysis, using a win-ratio and win-odds approach, finerenone demonstrated a reduction in heart failure events compared to placebo

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KEY POINTS:

• Finerenone, a non-steroidal mineralocorticoid (MRA), increased serum potassium levels more often than placebo. However, adverse events from hyperkalemia were rare
• The incidence of cardiovascular death or heart failure exacerbation was lower in patients using finerenone, even when serum potassium was elevated, as compared to use of the placebo group with a normal serum potassium

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Key Points:

• Transthyretin amyloidosis (ATTR-CM) is a fatal disease caused by the deposition of misfolded amyloid protein in the heart, leading to heart failure and poor cardiovascular outcomes.
• In the HELIOS-B trial, vutrisiran, an RNA interference therapeutic, significantly reduced all-cause mortality and cardiovascular (CV) events in patients with ATTR-CM.
• This prespecified analysis showed that worsening heart failure (HF) portends worse outcomes, including all-cause mortality and CV events, among ATTR-CM patients.
• Vutrisiran significantly reduced the risk of outpatient worsening HF and the composite of all-cause mortality and recurrent CV events compared with placebo.

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Key Points

• Observation data has suggested that improving cardiometabolic risk factors after AF ablation may reduce the recurrence of arrythmias.
• The ARREST-AF trial provides randomized controlled evidence demonstrating the benefits of a physician-led clinic focusing on risk factor modification (RFM) in reducing arrhythmia recurrence at 12 months.
• Patients in the RFM group were significantly more likely to be free from recurrent arrhythmia and experienced improved AF symptom scores compared to those receiving usual care.
• Improvements in body weight, systolic blood pressure, glycemic control, and exercise capacity were also observed in the RFM group, underscoring the role of risk factor control in mediating the observed benefits.

Prior observational studies have pointed to the role of aggressive risk factor modification (RFM) in improving long-term outcomes after catheter ablation for atrial fibrillation (AF). However, randomized controlled trial data to validate this hypothesis has been lacking.

On November 18^th  2024, the results of “Aggressive Risk factor REduction STudy for Atrial Fibrillation (ARREST-AF) implications for ablation outcomes: A Randomized Clinical Trial” were presented at AHA Scientific Sessions 2024. The purpose of this study was to determine if attempts at intensive RFM after AF ablation improves outcomes.

This randomized controlled trial included 122 consecutive Australian adult patients with paroxysmal or persistent symptomatic AF undergoing catheter ablation (pulmonary vein isolation with additional ablation at operator discretion) who had a body mass index of ≥ 27 kg/m² and one additional cardiometabolic risk factor.  Patients with severe structural heart or systemic disease were excluded.  They were assigned in a 1:1 fashion at to RFM or usual care arm. Patients in the RFM arm received intensive risk factor management through a physician-led clinic, following AHA guideline-based recommendations. Patients in the usual care arm received standard, guideline-directed care for AF management. The primary endpoint was proportion of patients free from AF recurrence 12 months post-ablation. Secondary endpoints included changes in AF symptom severity, cardiometabolic risk factors, exercise capacity and need for redo ablation.

At 12 months, 66% of patients in the RFM group were free from AF recurrence at 12 months, compared to 42% in the usual care group, a significant difference (HR 2.18 [95% CI 1.25-3.70]; p=0.004).  In addition, AF symptom severity was significantly improved in the RFM group compared to the usual care group. The RFM group also had significantly improved body weight, glycemic control, and exercise capacity, indicating that the intervention was successful at achieving an improvement in control of major cardiometabolic risk factors.

Rajeev K. Pathak, MD, PhD, FACC, Director of Cardiac Electrophysiology at Canberra Heart Rhythm  in Garran, Australia, concluded: “Amongst patients with AF, elevated BMI and one additional cardiometabolic risk factor, aggressive risk factor management reduces arrhythmia recurrence in the 12-months following catheter ablation when compared with usual care.”

Key Points

• Obesity-related heart failure with preserved ejection fraction (HFpEF) is associated with increased left ventricular (LV) concentric remodeling and paracardiac adipose tissue (PAT), which may exacerbate HFpEF through systemic and myocardial inflammation.
• The cardiac magnetic resonance imaging (CMR) substudy of the SUMMIT trial demonstrated that tirzepatide, a dual GIP/GLP-1 receptor agonist, significantly reduces LV mass and PAT in patients with obesity-related HFpEF.
• Tirzepatide’s effects on cardiac structure and function correlated with weight loss and improvements in other clinical parameters, and may have contributed to its clinical efficacy in reducing heart failure events

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Key Points

• ATTR cardiac amyloidosis (ATTR-CA) is frequently diagnosed in older Black individuals with heart failure (HF), particularly in men over 75 years of age.
• The SCAN-MP study provides observational data showing an overall prevalence of 6.5% for transthyretin cardiac amyloidosis (ATTR-CA) among Black and Caribbean Hispanic individuals aged 60 and older with HF.
• Most cases of ATTR-CA (60.5%) were wild-type (ATTRwt-CA), while 39.5% were hereditary (ATTRv-CA) associated with the V142I TTR gene variant.
• Prevalence in Black participants was markedly higher than in Hispanic participants, emphasizing the importance of targeted screening in high-risk populations.
• A genotype-first approach would miss over half of affected individuals, as many cases are wild-type ATTR-CA, highlighting the importance of imaging in the diagnostic algorithm.

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Key Takeaways:

• The OPTION TRIAL assessed the safety and efficacy of WATCHMAN FLX in a post-ablation contemporary clinical AF patient population at risk of stroke.
• The trial showed that left atrial appendage closure after AF ablation was associated with a lower risk of non–procedure-related major or clinically relevant nonmajor bleeding compared with oral anticoagulation.

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Key Points:

• Over 6 million people in the US live with heart failure (HF), but national rates of GDMT treatment remain low
• Because pharmacists can prescribe medication and often manage chronic medical conditions, the PHARM-HF A&F study aimed to determine if education alone versus a treatment audit-and-feedback (A&F) system increased the frequency of HF medication adjustments
• The A&F arm demonstrated an increase in monthly encounters and medication adjustments compared to education alone, as well as an increase in MRA adjustments
• Though there were no significant differences in other GDMT adjustment between both arms, both arms demonstrated an increase in GDMT initiation and uptitration with longer-term follow-up needed to assess additional outcomes

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Key Points

• SUMMIT, a randomized control trial of tirzepatide versus placebo in patients with HFpEF and obesity, found that tirzepatide significantly reduced the risk of worsening heart failure events and improved physical functioning.
• This sub-analysis found that tirzepatide also led to a significant decrease in systolic blood pressure, estimated plasma blood volume, CRP, and troponin-T in this population, as well as an increase in eGFR, providing insights into the mechanisms by which tirzepatide exerts is positive clinical effects

Tirzepatide is currently approved by the US Food and Drug Administration to treat obesity. The SUMMIT trial demonstrated a positive effect of tirzepatide versus placebo on a composite of worsening heart failure events and cardiovascular mortality among patients with HFpEF and obesity, but its impact on biometric outcomes in this population is uncertain.

On November 17^th  2024, the results of “Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial” were presented at AHA Scientific Sessions 2024 with simultaneous publication in the Nature. The purpose of this mechanist secondary analysis was to determine the impact of tirzepatide on biometric measures of cardiometabolic health. .

The SUMMIT trial randomized 731 adults aged 40 or older with HFpEF (congestive heart failure with an EF ≥ 50%) and obesity (BMI ≥ 30 kgm²) to weekly injections of tirzepatide or placebo in a 1:1 fashion, and found that at a a median of 2 years of follow up, tirzepatide was associated with a significantly lower risk of cardiovascular death or a worsening heart failure events — driven primarily by a decrease in worsening heart failure  — as well as a significant improvement in KCCQ scores compared to placebo.  This secondary analysis found that tirzepatide, when compared to placebo, was also associated with  a reduction in systolic blood pressure (estimated treatment difference [ETD] – 5 mmHg [95% CI -7 to -3]; p<0.001), estimated blood volume (ETD -0.58 L [-0.63 to -0.52]; p < 0.001), C-reactive protein (CRP) (ETD -37.2% [-45.7 to -27.3]; p < 0.001), and troponin T (-10.4% [-16.7 to -3.6]; p = 0.003).  In addition, tirzepatide was also associated with a significant increase in eGFR (+1.85 ml/min/1.73 m2 [0.19–3.51]; p = 0.029) and borderline significant reductions in N-terminal prohormone B-type natriuretic peptide levels  and urine albumin–creatinine ratio.  In a post-hoc exploratory analysis, a decrease in estimated blood volume was significantly correlated with a decrease in systolic blood pressure, microalbuminuria, and improved functional status as measured by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score and 6-min walk distance. Similarly, a decrease in CRP was associated with a decrease in troponin-T levels. Overall, the hemodynamic effects were observed early in treatment, whereas the anti-inflammatory effects occurred later in the treatment course.

Dr. Barry A. Borlaug, MD, of the Mayo Clinic in Rochester, Minnesota concluded: “Tirzepatide reduced circulatory pressure-volume overload and mitigated end organ damage in the kidney and heart in patients with HFpEF and obesity, providing new insight into the mechanisms of benefit from tirzepatide in patients with obesity-related HFpEF.”

1. Borlaug, B.A., Zile, M.R., Kramer, C.M. et al.Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial. Nat Med (2024). https://doi.org/10.1038/s41591-024-03374-z

Key Points

• Three prior randomized trials including over two million adults in Denmark demonstrated that a variety of electronic message reminders, or “nudges”, to receive the influenza vaccination led to higher vaccination rates.
• This pre-specified pooled analysis evaluated the effect of this intervention among those with a history of recent acute myocardial infarction (AMI) compared to those with no AMI history, and found that nudges which highlighted the cardiovascular benefits of vaccination led to larger improvement in vaccine uptake in the AMI group, particular among those who had not been vaccinated in the prior season.
• Targeted electronic nudges may be a low-cost, highly scalable intervention to improve influenza vaccine rates among those with a history of AMI.

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Key Points:

• In patients after surgical bioprosthetic valves, it remains unclear if edoxaban is safe and effective in preventing valve complicates early after surgery.
• In this randomized clinical trial, 389 patients who had surgical bioprosthetic valves implanted were randomized to receiving either standard dose endoxaban or warfar.
• Edoxaban was found to be as safe and effective treatment option to warfarin after surgical bioprosthetic valve implantation.

There is a high incidence of thromboembolic events after bioprosthetic surgical valves. Society guidelines recommend warfarin for 3-6 months following valve implantation. However, the off-label use of direct oral anticoagulants (DOACs) following bioprosthetic surgical valve implantation is rising although its efficacy and safety is unknown.

The Efficacy and Safety of Edoxaban in Anticoagulant Therapy Early After Surgical Bioprosthetic Valve Replacement (ENBALV) trial was an investigator-initiated, open-label, multicenter, randomized clinical trial performed at 24 institutions in Japan. The study enrolled 410 patients at 24 institutions in Japan who had bioprosthetic valve replacement at the aortic and/or mitral position between May 2022 and January 2024; 389 patients were included in the final analysis.  Participants were randomized to receive either edoxaban (60 mg or 30 mg taken orally, once daily) or warfarin (administered orally, with dosing adjusted by monitoring the time taken for the patient’s blood to clot) for 12 weeks after surgery. The primary outcome was composite stroke or systemic embolism. The results of the trial were presented as a late breaking clinical trial at the American Heart Association on November 17, 2024.

Patients were ages 41-84 years old, with an average age of 73 years. The edoxaban group was 51% male and 49% female; the warfarin group was 63% male and 37% female. The study randomized participants after surgical bioprosthetic valve implantation in either the mitral or aortic position to either standard dose edoxaban (195 participants) or warfarin (194 participants).

A primary-outcome event occurred in 1 patient (0.5%) in the endoxaban arm and 3 patients (1.5%) in the warfarin arm (risk difference -1.03; 95% confidence interval [CI] -4.34 to 1.95) at 12 week follow-up. The incidence of major bleeding was higher in the endoxaban group compared to the warfarin group although not clinically significant (risk difference 3.07; 95% confidence interval [CI] –0.67 to 7.27). No fatal bleeding or intracranial hemorrhage was observed in the edoxaban group while one patient had fata intracranial bleeding in the warfarin group.

Limitations of the trial include open-label protocol, heterogenous initiation of anticoagulation at the discretion of the surgeon, short time in the therapeutic range for the warfarin arm (19.0% ± 21.6%), and no TAVR patients included.

In the late breaking presentation at the American Heart Association Scientific Sessions, Dr. Chisato Izumi concluded that “the ENBALV trial provides the first large-scale evidence demonstrating that edoxaban is a potential alternative anticoagulant therapy in patients early after bioprosthetic valve surgery.”

Key Points:

• Transthoracic echocardiography is foundational to diagnosis and evaluation of myriad conditions, but image interpretation and results reporting depends on manual reporting
• As opposed to previous applications of artificial intelligence (AI) to TTE that have focused on individual views and medical conditions, PanEcho is a view-agnostic, multi-task AI model trained on 1.23 million echo videos that can perform 39 different TTE reporting tasks
• PanEcho demonstrated a median area under the receiver operating characteristic curve (AUC) of 0.91 across 18 different classification tasks as well as minimal mean absolute error (MAE) when estimating continuous parameters, ability to identify useful views for a specific task, and translation of accurate interpretation to novel pediatric populations
• Pan-Echo represents a view-agnostic, multi-task, externally validated, open-source AI model that can accurately interpret images and produce reports across a variety of views and patient populations

Transthoracic echocardiography (TTE) is key to diagnosis and evaluation of myriad conditions. However, interpretation of imaging and reporting of findings relies on manual reporting. Among varied disciplines, artificial intelligence (AI) is said to automate processes, theoretically increasing accuracy and efficiency exponentially. Current applications of AI to TTE have traditionally focused on individual echo views and medical conditions. Here, the investigators developed PanEcho, a view-agnostic, multi-task AI model that automates TTE interpretation across different views and acquisitions for all key echocardiographic metrics and notable findings.

The investigators developed PanEcho using 1.23 million echocardiographic videos from 33,927 TTE studies performed at a health system in New England from 2016 to 2022. The model can perform 39 different TTE reporting tasks, including myocardial and valvular structure and function from any parasternal, apical, and subcostal views, including B-mode and color Doppler. PanEcho has an image encoder to learn spatial features, a Transformer (a neural network converting input to output) for temporal modeling, and task-specific output heads. In this study, PanEcho was evaluated on a distinct patient cohort from July to December 2022 as well as two external California-based cohorts from 2008 to 2020 to assess its diagnostic performance and ability to serve as a foundation model for fine-tuning in new domains.

PanEcho demonstrated a median area under the receiver operating characteristic curve (AUC) of 0.91 across 18 different classification tasks. Selected results include detection of severe aortic stenosis (AS) with 0.99 AUC, moderate-severe left ventricular (LV) systolic dysfunction with 0.98 AUC, moderate-severe LV dilation with 0.95 AUC, among others. Furthermore, the model estimates continuous metrics with a medial normalized mean absolute error (MAE) of 0.13 across 21 tasks (e.g. defining LV ejection fraction (EF) with 4.4% MAE). PanEcho’s multi-view evaluation demonstrates its ability to determine which views are more informative for each task. In addition, PanEcho’s learned representations transfer efficiently to LVEF estimation in pediatric population, outperforming current approaches (3.9% MAE vs 4.5% for the next-best).

Ultimately, the investigators conclude that PanEcho is a view-agnostic, multi-task, externally validated, open-source AI model that can accurately interpret images and produce reports across a variety of views and patient populations. Currently, PanEcho is limited by retrospective validation in previously acquired datasets. However, next steps include prospective validation in real-world patient care settings as well as evaluation of its utility among settings utilizing portable and point-of-care ultrasound (POCUS).

Key Points:

The global burden of hypertension (HTN) with high globally at 1.3 billion people and locally in India with 300 million affected
Despite making up 25% of the global population, there has never been a randomized controlled trial to investigate the optimal initial guideline-recommended combination therapy to treat HTN in those of Indian ancestry
Nearly 2000 patients were randomized to one of the three recommended initial HTN combination therapies to determine the mean change in 24-hour ambulatory systolic blood pressure (SBP) as well as other secondary outcomes
All three groups demonstrated a 14mmHg reduction in ambulatory SBP, suggesting that any of the three recommended combination therapies is reasonable for initial HTN treatment in patients of Indian ancestry

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Key Points:

• Though physical inactivity leads to poor cardiovascular outcomes, especially for those with cardiovascular disease, few studies have been performed to validate the utility of effective lifestyle interventions in this patient population
• The MyoMobile Study was a single-center randomized controlled trial to assess the effect of a personalized mobile health intervention compared to usual care on physical activity level in patients with heart failure with preserved ejection fraction (HFpEF)
• The trial compared three patient groups – usual care, patients receiving a pedometer to measure daily step count (tracking arm), and patients receiving an individualized, app-based physical activity coaching based on pedometer-based assessment of daily step count (coaching arm) – to assess change in daily step count as well as other secondary outcomes
• The coaching arm demonstrated a significant increase in daily step count compared to not only usual care, but also the tracking arm, which may demonstrate the benefits of personalized coaching for lifestyle modification therapy

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Key Points

• Maximizing lipid lowering therapy (LLTs) to optimize residual cardiovascular disease (CVD) risk after acute coronary syndrome (ACS) is usually a stepwise approach that can take months or years for many patients.
• This randomized control trial tested whether a decision support system (DSS) that provided information about residual CVD risk after ACS as well as the potential benefits of various LLTs would lead to earlier optimization compared to standard of care (SoC) pathways.
• The DDS did not significantly improve intensity of LLT treatment of percentage of patients receiving LDL-C goals within the study timeframe – however the favorable trends observed implies that this system may have value in other settings where the current SOC performance is lower than in the trial.

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KEY POINTS:

• Exenatide is a glucaon-like-peptide-1 agonist (GLP-1) improves glycemic control, and other medications in this class, appear to reduce the risk of cardiovascular disease
• The GLORIOUS Trial evaluated intravenous exenatide vs placebo in patients undergoing coronary artery bypass (CABG) or aortic valve replacement (AVR) with cardiopulmonary bypass (CPB)
• After a median follow-up of 5.9 years, no significant difference was observed in composite endpoint death, stroke, renal failure requiring dialysis, and new or worsening heart failure between the exenatide and placebo groups

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Key Points:

• Familial chylomicronemia syndrome (FCS) is characterized by extremely high plasma triglycerides (TGs) due to failure of clearance of chylomicrons, of which the most severe sequela is acute pancreatitis (AP)
• The PALISADE trial investigated a novel siRNA therapeutic, plozasiran, hypothesized to treat FCS by targeting the main regulator implicated, APOC3, which precipitates persistent chylomicronemia by inhibiting lipolysis and decreasing hepatic clearance of triglyceride-rich lipoproteins (TRLs)
• The investigators previously randomized groups to low-dose or high-dose plozasiran vs placebo to investigate primary outcome of median percent change in TGs at 10 months, as well as notable secondary outcomes, including overall reduction in TGs and APOC3 as well as reduced risk of AP, finding that plozasiran met all clinical endpoints, including reduction in TGs, APOC3, and reduced risk of AP
• The authors now present the longer-term effects of therapy, noting rapid and significant (>80%) reductions in TGs and APOC3, independent of gene variants, as well as sustained reduction of TG levels below the threshold to prevent AP among >50% of included patients

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Key Takeaways:

• The VANISH2 trial compared catheter ablation with systematic antiarrhythmic drug therapy as a first-line treatment strategy in patients with an ICD ischemic cardiomyopathy, and ventricular tachycardia who had no history of nonresponse to antiarrhythmic drug therapy.
• Catheter ablation significantly reduced the composite primary outcome (death, VT storm, ICD shock, and VT emergency treatment) compared with antiarrhythmic drug therapy (HR, 0.75; 95% CI, 0.58–0.97; P=0.03).
• Sustained VT requiring treatment below the detection limit of an ICD was notably reduced in the catheter ablation group (HR, 0.26; 95% CI, 0.13–0.55; P<0.001).
• Mortality rates were similar between groups, with no statistically significant difference (HR, 0.84; 95% CI, 0.56–1.24; P=0.38).
• Catheter ablation demonstrated a comparable safety profile, with fewer drug-related adverse events compared to antiarrhythmic drugs.

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