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:

• The 30-day ECLS SHOCK study demonstrated no benefit to up-front ECLS in the reduction of 30-day mortality in acute, infarct-related cardiogenic shock.
• At one year, there were similarly no differences in the primary endpoint of all-cause mortality between ECLS and control. Additionally, there were no differences in the secondary outcomes of CV mortality, readmissions, and repeat revascularization.
• Patients receiving ECLS had significantly higher moderate or extreme pain at one year relative to those in the control arm, with no differences in other quality of life measures.

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Key Points:

• While inflammation is critical to the pathogenesis of atherosclerosis, few available anti-inflammatory treatments have been tested in ACS.
• In IVORY FINALE, low-dose interleukin 2 (IL-2) was compared to placebo in ACS. The primary endpoint was change in arterial inflammation, as measured by PET scan. Safety and tolerability were also assessed.
• In the primary analysis, IL-2 resulted in a significant reduction in arterial inflammation in the index vessel on PET. Over a median of 2.6 years of follow-up, IL-2 also decreased MACE compared to placebo.

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Key Points:

• The RHEIA trial found that TAVI was superior to surgical aortic valve replacement (SAVR) in women with severe aortic stenosis, significantly reducing the composite endpoint of all-cause mortality, stroke, and rehospitalization for valve-related symptoms or worsening heart failure.
• The reduction in the primary endpoint was primarily driven by a significant decrease in rehospitalizations for valve- or procedure-related symptoms in the TAVI group compared to the SAVR group.
• TAVI demonstrated clear advantages over SAVR, suggesting that TAVI could be the preferred therapy for women with severe symptomatic aortic stenosis.

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Key Points:

• Anthracycline toxicity is an important cause of cardiomyopathy; it is unclear whether prophylactic treatment with ACE inhibitors could mitigate this risk.
• In PROACT, enalapril was compared to standard of care in individuals undergoing anthracycline treatment for breast cancer or NHL. The primary endpoint was myocardial injury (defined as cTnT≥14 ng/L). 
• Enalapril did not result in a significant reduction in anthracycline toxicity as measured by myocardial injury, LVEF, or GLS a month after chemotherapy completion.

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Key Points:

• IV TXA is used to prevent peri-operative bleeding in cardiac surgery, but it carries a risk of seizure. It is hypothesized that topical TXA may reduce this risk of seizure.
• In DEPOSITION, topical and IV TXA were compared in individuals undergoing cardiac surgery. The primary endpoint was seizure. Authors also investigated differences in RBC transfusions between arms.
• Topical TXA did not result in a significant difference in peri-operative seizures, but it did increase RBC transfusion requirement relative to IV TXA.

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Key Points:

• Despite the high symptomatic burden, very few effective treatments exits for symptomatic, non-obstructive HCM.
• In IMPROVE-HCM, a novel cardiac mitotrope (ninerafaxstat) was compared to placebo in non-obstructive HCM. The primary efficacy endpoint was change in KCCQ score from baseline. Safety and tolerability were also assessed.
• In the primary intention-to-treat analysis, ninerafaxstat did not improve symptoms; however, when restricting the population to patients with baseline limitation by KCCQ (or NYHA III), treatment resulted in a significant improvement in HF symptoms. Ninerafaxstat also improved exercise capacity on CPET in the total sample.

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Key Points:

• Benzodiazepine use contributes to delirium before and after cardiac surgery, but intra-operative benzodiazepine use has not been well-studied.
• In B-Free, a restrictive intraoperative benzodiazepine strategy was compared with a liberal benzodiazepine strategy in the reduction of post-operative delirium.
• In the primary intention-to-treat analysis, the restrictive benzodiazepine strategy did not result in a significant reduction in post-operative delirium. However, this endpoint was significantly reduced in the restrictive arm using either an on-policy analysis approach or after excluding patients receiving pre-operative benzodiazepines. 

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Key Points:

• Inter-atrial shunting (IAS) may provide a useful opportunity to dynamically regulate left atrial pressure in heart failure.
• In the RELIEVE-HF study, IAS was compared with placebo in patients with at least a 6-month history of HF, across all LVEF categories and HF etiologies. The primary endpoint was a hierarchical composite of all-cause death, transplant or LVAD placement, all HF hospitalizations, and change in KCCQ score from baseline to 12 months; the primary safety endpoint was a composite of major adverse cardiac or neurologic events over 30 days.
• IAS was well-tolerated with zero adverse safety events, but it did not result in a significant reduction in the primary endpoint. However, in exploratory pre-specified stratified analyses by LVEF, IAS appeared to cause harm in patients with HFpEF and confer benefit in HFrEF.

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Key Points:

• Severe hypertriglyceridemia portends high risk of both CVD and acute pancreatitis, but there are limited effective treatment options.
• A novel RNA interference (RNAi) therapeutic plozasiran can reduce APOC3, a mediator of triglyceride elevation.
• In the Phase 2B trial SHASTA-2, two doses of plozasiran were compared with placebo in long-term (24 and 48 week) reduction of triglycerides and other cholesterol pathway mediators.
• All doses of plozasiran was well-tolerated and resulted in sustained reduction in triglycerides, APOC3, and remnant cholesterol with increased HDL-C by 24 weeks, with a still-significant but attenuated effect at 48 weeks.

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Key Points:

• Cardiogenic shock (CS) mortality remains high despite increased utilization of mechanical circulatory support. Specifically, no randomized data has supported the use of Impella CP in CS.
• In DanGer Shock, routine use of Impella CP was compared with standard of care in selected individuals with cardiogenic shock after STEMI.
• Impella CP use was associated with a 13% reduction in 6-month all-cause-mortality but increased rates of both ischemic and hemorrhagic adverse events.

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Key Points:

• Post-MI adverse cardiovascular events remain high despite robust evidence-based antiplatelet, statin, and anticoagulant therapy.
• Cholesterol efflux is impaired post-MI and has been associated with  short- and long-term MACE. A novel human plasma–derived apolipoprotein A1 (CSL112) was developed to increase cholesterol efflux capacity with the goal of improving cholesterol efflux post-MI.
• In the AEGIS-II study, intravenous infusions of CSL112 were compared with placebo in patients with type I acute MI. The primary endpoint was 90-day CV death, MI, or stroke.
• CSL112 did not result in a significant reduction in the primary endpoint; however, patients treated with CSL112 infusions had numerically lower rates of CV death and MI, type-1 MI, and stent thrombosis-related MI compared to placebo. 
• In an exploratory analysis, CSL112 significantly reduced the primary endpoint in a subgroup of individuals with LDL ≥100 mg/dL.

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Key Points:

• Up to 1 in 10 women experience a hypertensive disorder of pregnancy, which is associated with long-term cardiovascular disease. However there are no established interventions to reduce risk post-partum.
• The POP-HT study examined the impact of a targeted physician-optimized postnatal BP control regimen on long-term BP control and cardiac remodeling.
• Physician-Optimized post-partum BP control resulted in a significant reduction in both systolic and diastolic BP at 9 months, in addition to BP-related postnatal admissions and evidence of adverse cardiac remodeling on both cardiac MRI and echocardiogram.

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Key Points:

• Uncontrolled hypertension is a major public health concern, and this condition is often primarily driven by the renin-angiotensin (RAAS) pathway.
• A new RNA interference therapy, Zilebesiran, was developed to target to most upstream precursor of the RAAS pathway (angiotensinogen). This study was a Phase 2 study examining the safety and efficacy of zilebesiran.
• A single dose of subcutaneous zilebesiran resulted in sustained BP reduction with low rates of adverse events over 6 months.

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Key Points:

• Despite the advent of PCSK9 inhibitors, the majority of patients with familial hypercholesterolemia do not meet their LDL-C targets with standard therapies. 
• VERVE-1 is a novel CRISPR base editing medication which was designed to inactivate hepatic PCKS9 with a single DNA base pair change, thus reducing LDL-C.
• In this study, the highest dose of VERVE-101 treatment resulted in a sustained >55% LDL-C reduction at 180 days. VERVE-101 was generally well tolerated, with mild infusion reactions at high doses and two observed severe adverse CV events which were attributed to underlying severe ASCVD.

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Key Points:

• There are currently no approved targeted therapies for the reduction of Lp(a).
• In this Phase I study, a novel siRNA therapy (lepodisiran) was tested in escalating doses and compared to placebo in 48 patients. Lp(a) concentrations and safety events were examined for 48 weeks.
• Single-dose lepodisiran administration resulted in up to 94% reduction in Lp(a) at 48 weeks and was generally well-tolerated, supporting further development of this therapy.

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Key Points:

• Since the advent of novel HeartMate 3 LVAD technology with lower thrombotic risk, the clinical utility of continuing to add aspirin to the antithrombotic strategy has not been established.
• In the ARIES-HM3 study, an aspirin exclusion strategy (ie, Vitamin K antagonist [VKA] + placebo) was compared with the typical dual VKA/ASA therapy in patients with a HeartMate 3 LVAD. The primary endpoint was survival free of any non-surgical major hemocompatibility related adverse event one year post implant.
• Aspirin avoidance resulted in fewer bleeding events and hospitalizations for bleeding complications without any concurrent increase in thrombosis or mortality.

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Key Points:

• Out-of-pocket costs for GDMT in HFrEF have risen substantially with the advent of novel effective therapies. However, there is limited information regarding the utility of comprehensive cost disclosure in informing patient and clinician decision-making regarding prescribing GDMT.
• The POCKET-COST-HF study was a stepped-wedge cluster randomized trial examining the utility of a tailored, comprehensive cost disclosure intervention on a primary endpoint of cost-informed decision-making, ascertained by transcription of audio recordings of a clinic visit for HF.
• Comprehensive cost disclosure resulted in a higher proportion of encounters in which cost of medication was discussed, with further studies needed to inform the potential impact on medication prescribing and implementation strategies. 

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Key Points:

• While myocarditis is an inflammatory condition, there have not yet been trials demonstrating the benefit of anti-inflammatory therapies in the treatment of acute myocarditis.
• In the ARAMIS study, subcutaneous anakinra was compared with placebo in patients with acute myocarditis diagnosed on CMR presenting with chest pain and troponin elevation. The primary endpoint was number of days alive free from myocarditis complications.
• Anakinra use did not result in a significant change in number of days free from myocarditis complications but was well-tolerated and safe.

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Key Points:

• Diuretic requirement Is a major contributor to hospital length-of-stay for HF admissions, but the optimal strategy of diuretic optimization has not yet been established. Spot urinary sodium measurement and subsequent natriuresis-guided diuretic adjustment may refine diuretic dosage in the setting of insufficient diuretic response.
• In the PUSH-AHF study, natriuresis-guided therapy was compared with standard of care in patients hospitalized with acute HF. The two primary endpoints were a) natriuresis over 24 hours and b) first occurrence of all-cause mortality or heart failure rehospitalization after 180 days.
• Natriuresis-guided therapy resulted in significantly increased natriuresis over 24 hours without a significant difference in time to all-cause mortality or heart failure rehospitalization.

The duration of acute HF hospitalization is often driven by diuresis requirement, but the optimal strategy of in-hospital diuresis has not yet been established. For those with insufficient diuretic response, assessment of urinary sodium may help monitor diuretic response and guide further therapy. In a breaking presentation at the 2023 ESC Congress today, Dr. Jozine ter Maaten (University Medical Centre Groningen ) and her team presented their study: “PUSH-AHF: Natriuresis guided therapy in acute heart failure.”

The PUSH-AHF trial (NCT04606927) was a randomized, open-label single-center trial of adult patients with a primary inpatient diagnosis of acute heart failure with an intravenous diuretic requirement that compared natriuresis-guided therapy with standard of care diuresis. Natriuresis-guided therapy was dictated by spot urinary sodium measurements; a spot sodium <70 mmol/L indicated insufficient response and resulted in diuretic therapy adjustment.  Key exclusion criteria were non-cardiac dyspnea or severe renal impairment requiring dialysis. The two primary outcomes were total natriuresis after 24 hours and first occurrence of all-cause mortality or heart failure rehospitalization after 180 days.

A total of 310 patients were 1:1 randomized to either natriuresis-guided therapy or standard of care. The median age was 74, and 45% were women. Participants receiving natriuresis-guided therapy had a significant increase in natriuresis at 24 hours (409±178 vs 345±202 mmol, p=0.0061).  However, there were no significant differences in time to all-cause mortality or heart failure rehospitalization after 180 days (HR 0.92, 95% CI 0.62-1.38, p=0.698). The secondary endpoints of 48-hour natriuresis and both 24- and 48-hour diuresis were all increased in the intervention arm (all p<0.02). There was no difference in hospital length-of-stay between the two groups. Natriuresis-guided therapy was safe and well-tolerated.

When discussing the clinical implications of the study at the ESC Congress press conference, Dr. ter Maaten stated: “The results of the PUSH-AHF trial are directly implementable to improve decongestive treatment as spot urinary sodium values are easy to obtain, inexpensive and widely available…natriuresis guided therapy was safe and is a first step to a personalized treatment approach in patients with acute heart failure.”