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:

• Daily sodium intake remains high (on average ~3,500 mg/day), despite recommendations from the AHA and WHO to limit sodium intake to around 2,000 mg/day. 
• Salt-sensitivity to BP (SSBP) is an emerging concept supporting the notion that both normotensive and hypertensive individuals can have BP responses to their dietary sodium concentration. 
• The CARDIA-SSBP trial was a prospective, multicenter, randomized cross-over study that enrolled 228 participants to 1 week of either a high sodium diet (with up to 2,200 mg of sodium added/day) or a low sodium diet (with standardized meals containing 500 mg of sodium added/day), followed by another week crossing over to the other diet. At baseline and at the end of each week of diet, 24-hr ABPM and 24-hr urine collections were performed. 
• The low-sodium diet resulted in a significant reduction in median SBP of 6 mm Hg, which was similar to the average effect that would be observed with 12.5 mg of hydrochlorothiazide. On the other hand, further increases in daily sodium intake did not result in any significant increase in BP in this cohort – most likely as the baseline diets were already saturated in sodium.
• In conclusion, these data support that clinically meaningful lowering of BP through dietary sodium reduction can be achieved safely and rapidly within 1 week, with a magnitude comparable with that of a common first-line antihypertensive medication.

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Key Points

• This was the first randomized trial to evaluate the safety and efficacy of everolimus and low-dose tacrolimus in pediatric heart transplant recipients.
• The open-label trial demonstrated that this combination is safe compared to standard dose tacrolimus and mycophenolate mofetil but was not associated with a lower burden of coronary allograft vasculopathy, rejection, and chronic kidney disease.
• TEAMMATE was limited by lower event rates than expected and challenges related to protocol adherence due to the COVID19 pandemic.

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Key points:

• PCI is often performed for chronic stable angina, but current evidence is unclear to what extent the benefit is physiologic vs placebo
• This trial compared PCI with placebo-procedure in stable angina patients not on antianginal therapy with primary outcome of angina symptom assessment
• PCI was significantly associated with decreased angina symptoms measured by an angina symptom score compared to placebo

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Key Points:

• Intensive blood pressure (BP) lowering intervention was tested on hypertensive patients in rural China.
• In this four year blood pressure intervention program in rural China,  the intervention, led by non-physician community health-care providers, significantly reduced systolic blood pressure and the risk of all-cause dementia.
• Serious adverse events were less frequent in the intervention group, indicating the safety of the approach.

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Key Points

• Anemia is common among individuals with acute myocardial infarction, however, transfusion thresholds and targets remain uncertain.
• The MINT trial randomized 3,506 patients with acute myocardial and anemia (hemoglobin concentration < 10 g/dL) to a restrictive transfusion strategy (transfusion permitted if hemoglobin was less than 8 g/dL or in the event of anginal symptoms despite medications) or a liberal strategy (transfusion when hemoglobin was less than 10 g/dL).
• At 30-days the primary endpoint of all-cause death or recurrent myocardial infarction was not statistically different between the two strategies. 

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Key Points 

• This trial of patients with acute myocardial infarction (AMI) and impaired left ventricular (LV) systolic function found that dapagliflozin significantly improved clinical and cardiometabolic outcomes compared with placebo. 
• There was no significant difference in clinical events rates, which were low in both groups. 
• The innovative registry-based clinical trial design helped facilitate efficient patient recruitment and outcomes ascertainment.  

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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.”

Key Points:

• In hospitalized COVID-19 patients, treatments targeting the virus’s pathobiology (e.g. dysregulated immune response, inflammation, etc.) has been shown to improve outcomes
• Sodium glucose co-transporter 2 (SGLT2) inhibitors affect similar pathobiology and may lead to organ protection in acute illness, but their role in hospitalized COVID-19 patients is uncertain
• In this meta-analysis, SGLT2 inhibitors did not demonstrate decreased 28-day all-cause mortality compared with usual care or placebo in hospitalized COVID-19 patients

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Key Points:

• Contrast-induced nephropathy (CIN) is a clinical condition that refers a deterioration in kidney function after contrast exposure and is a known complication of coronary angiography
• Some studies suggest that strategies to replace nitric oxide in the body may be beneficial because nitric oxide is deficient in CIN; inorganic (dietary) nitrate is metabolized in the body to nitric oxide, and previous studies have shown protective effects on the kidneys
• The NITRATE-CIN trial examined the efficacy of inorganic nitrate for the prevention of CIN in patients with non-ST elevation ACS (NSTE-ACS) referred for invasive coronary angiography
• Compared to placebo, inorganic nitrate reduced CIN, improved kidney outcomes at three months, and reduced major adverse cardiac events (MACEs) at 12 months in patients at risk of kidney injury undergoing coronary angiography for acute coronary syndrome (ACS)

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Key Points

• Evidence suggests that catheter ablation for atrial fibrillation (AF) is associated with improved cardiovascular outcomes compared to medical therapy in patients with heart failure (HF). However, its use in a population exclusively with end-stage HF eligible for heart transplant is unknown.
• The CASTLE-HTx trial demonstrated a significant decrease in a composite end-point of all-cause mortality, worsening of HF requiring a high urgent transplantation, or implantation of a ventricular assist device as bridge to transplantation therapy with atrial fibrillation ablation compared to medical therapy.

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Key Points:

• The DICTATE-AHF trial explored early initiation of the SGLT2 inhibitor dapagliflozin in acute decompensated heart failure (ADHF) patients.
• The trial did not show a statistically significant improvement in diuretic efficiency with dapagliflozin compared to structured usual care.
• However, exploratory analyzes indicated that dapagliflozin improved decongestion and led to earlier hospital discharge without worsening safety outcomes.

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Key Points

• This trial randomizing patients with an indication for initial dual chamber (DDD) permanent pacemaker implantation (PPI) for sinus node dysfunction (SND) to a base rate of 60 beats per minute (BPM) with rate adaptive pacing (DDDR-60) or base rate of 40 BPM with non-rate adaptive pacing (DDD-40) found that there was no difference in the primary endpoint of atrial fibrillation (AF) lasting more than 6 minutes during 2 years of follow up.
• There was also no difference in the secondary endpoints of AF lasting more than 6 or 24 hours, progression to permanent or persistent AF, cardioversions for AF, all cause mortality, quality of life, or 6 minute walk test.
• However, rates of syncope were significantly higher in the DDD-40 group, as were the rates of crossover from the DDD-40 to the DDDR-60 group.
• These results indicate that minimizing atrial pacing in patients SND did non prevent AF but did lead to an increased risk of pre-syncope or syncope.

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Key Points:

• The RIGHT trial assessed the benefit of post-procedural anticoagulation (PPA) after primary percutaneous coronary intervention (PCI) in ST-segment elevation myocardial infarction (STEMI) patients.
• The trial found that overall, PPA did not result in a significant reduction in adverse outcomes compared to placebo in a low-to-intermediate risk population.
• There was a significant interaction between the type of anticoagulant used and the primary endpoint, with enoxaparin showing potential benefit while unfractionated heparin and bivalirudin did not.

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Key Points

• This trial randomizing patients at high bleeding and/or ischemic risk who had successfully completed 9-12 months of dual anti-platelet therapy (DAPT) following initial percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) to an additional 9 months of either continued DAPT or clopidogrel monotherapy plus placebo found that patients in the clopidogrel monotherapy arm had significantly lower rates of clinically relevant bleeding and major adverse cardiovascular and cerebral events (MACCE; defined as all-cause death, MI, stroke, and clinically indicated revascularization).
• These data indicate that among patients at high bleeding and/or ischemic risk who undergo PCI for ACS, after initial 9-12 months of DAPT, de-escalation to clopidogrel alone is superior to continuation of DAPT for 9 additional months in terms of both bleeding and ischemia.
• The exact duration of clopidogrel monotherapy following the initial 9-12 months of DAPT in these patients remains uncertain. When and if they should de-escalate to aspirin monotherapy or if they should remain on lifelong clopidogrel is an area of future research.

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Key Points

• This pragmatic trial randomizing patients to optical coherence tomography (OCT)-guided or intravascular ultrasound (IVUS)-guided percutaneous coronary intervention (PCI) found that OCT was non-inferior to IVUS for a composite outcome of cardiovascular death, target vessel myocardial infarction, or ischemia-driven target vessel revascularization.
• These data indicate that OCT has similar outcomes compared with IVUS in PCI across a broad range of coronary lesions, though patients with chronic kidney disease and ST-elevation myocardial infarction (STEMI) were excluded.

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Key Points

• This metanalysis integrating data from ILUMIEN IV and OCTOBER Trials with 18 prior randomized trials found that intravascular imaging (IVI) with intravascular ultrasound (IVUS) or optical coherence tomography (OCT) was associated with a 31% reduction in target lesion failure (TLF) compared to angiography alone.
• In addition, there were statistically significant reductions in all-cause death, all myocardial infarction (MI), and target vessel revascularization (TVR), a novel finding.
• OCT and IVUS performed similarly compared against angiography and one another.
• These data indicate that IVI with either OCT or IVUS is associated with better long-term clinical outcomes compared to angiography alone. The authors plan to update the analysis with data from the OCTIVUS trial, also presented the same day at ESC.

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