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.

Continue reading →

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.

Continue reading →

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. 

Continue reading →

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.

Continue reading →

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:

• Sudden cardiac death causes a fifth of all deaths in industrialized countries, but survival to hospital discharge remains low.
• Transfer to a specialized, cath-lab capable cardiac arrest center may expedite care of patients with an ischemic cause of arrest.
• This multicenter randomized trial compared transfer to a specialized cardiac arrest center with the nearest ED in patients with a resuscitated out-of-hospital cardiac arrest (OHCA). The primary endpoint was 30-day all-cause mortality.
• There were no differences in the primary endpoint of all-cause mortality between the two transportation strategies, nor any difference in the secondary endpoints of 3-month mortality and neurological outcome.

Continue reading →

Key Points:

• The use of ECLS has increased substantially over the past decade despite stagnant, high mortality in cardiogenic shock.
• This multicenter randomized trial compared ECLS with control in patients with acute MI-related cardiogenic shock. The primary endpoint was 30-day all-cause mortality.
• There were no differences in the primary endpoint of all-cause mortality between ECLS and placebo; however, ECLS resulted in higher rates of moderate-to-severe bleeding and peripheral ischemia requiring intervention.

Continue reading →

Key Points:

• Qiliqiangxin is a traditional Chinese herbal medicine extract which has been approved since 2004 for the treatment of HF in China.
• This multicenter, double-blind, placebo-controlled trial compared qiliqiangxin with placebo amongst patients with HFrEF (EF<40%). The primary endpoint was a composite of CV death and HF hospitalizations.
• Over a median follow-up of 18 months, qiliqiangxin use resulted in a reduction in the composite primary endpoint.

Continue reading →

Key Points:

• More than 80% of patients with HFpEF are overweight or obese, but there has not yet been a study examining the use of weight-loss agents in body weight reduction or HF symptomatology in HFpEF.
• In the Step-HFpEF study, subcutaneous once-weekly semaglutide was compared with placebo in patients with HFpEF and obesity. The two primary endpoints were change of KCCQ-CCS and body weight from baseline after 52 weeks of treatment.
• Semaglutide use resulted in a significant reduction in both heart failure symptomatology and body weight at 52 weeks.

Continue reading →

Key Points:

• Both inflammatory risk and hyperlipidemia and crucial risk factors for MACE in patients at high risk of CVD.
• In a large collaborative study of patients combining data from the PROMINENT (N = 9,988), REDUCE-IT (N = 8,179) and STRENGTH (N = 13,078) trials, the effect of residual inflammatory risk (as measured by hsCRP) and LDL-C levels on MACE were assessed.
• Residual inflammatory risk as assessed by hsCRP was a stronger determinant of risk for future cardiovascular events and death than residual cholesterol risk as assessed by LDL-C.

Continue reading →

Key Points:

• There have been conflicting data on the role and recommended dosage of anticoagulation in non-critically-ill patients with COVID-19.
• In the open-label FREEDOM COVID study, therapeutic anticoagulation was compared with prophylactic doses of enoxaparin in patients hospitalized for COVID-19. The primary endpoint was a 30-day composite of all-cause mortality, requirement For ICU level-of-care, systemic thromboembolism, or ischemic stroke.
• Therapeutic anticoagulation did not result in any significant differences in the composite endpoint, but it did result in lower 30-day mortality and endotracheal intubation compared with prophylaxis.

Continue reading →

Key Points:

• Sotatercept is a novel activin signaling inhibitor which was designed to target pulmonary vascular remodeling in PAH.
• In the STELLAR study, sotatercept was tested against placebo on a background of baseline PAH therapy in adults with WHO II/III PAH. The primary endpoint was change in 6MWD at 16 weeks.
• Sotatercept resulted in an improvement in 6MWD, PVR, NT-proBNP, and a composite of time to clinical worsening and all-cause mortality at 16 weeks compared to placebo.

Continue reading →

Key Points:

• SGLT2i therapy reduces HF hospitalizations and CV mortality in HFpEF, but the mechanism is not yet clear.
• In this single-center, double-blinded RCT, patients with HFpEF were randomized to dapagliflozin or placebo and underwent exercise and resting hemodynamics at baseline and at 24 weeks.
• Dapagliflozin resulted in reduced resting and exercise PCWP, weight, and plasma volume relative to placebo.

Continue reading →

Key Points:

• Macitentan and Tadalfil are frequently used in combination for PAH, which opens up the possibility of a fixed-dose combination pill.
• In the DUE study, macitentan/tadalafil FDC therapy was compared against macitentan and tadalafil monotherapy. The primary outcome was PVR reduction at 16 weeks.
• M/T FDC resulted in a significant reduction in PVR at 16 weeks compared to either macitentan or tadalfil monotherapy. There was a non-significant trend towards reduction in 6MWD at 16 weeks.

Continue reading →

Key Points:
 The prognostic significance of the V122I variant (associated with wt-ATTR) in Black women has not yet been established.
 A substudy of the WHI aimed to establish the association of the V122I variant with a composite of CVD and all-cause mortality in Black Women.
 The V122I variant was associated with increased composite CVD and all-cause mortality in Black women; this association was particularly significant for women age 60+.

Continue reading →

Key Points:

• There have been limited data regarding the biomarkers that may predict the development and severity of preeclampsia.
• hs-cTnI was significantly elevated in pregnant women who would later develop preeclampsia starting at 14 weeks. A cutoff hs-cTnI value of >2.2pg/ml at 14 weeks and >2.6pg/ml at 26 weeks had a combined 100% negative predictive value for predicting severe preeclampsia in women at high a prior risk.

Continue reading →

Key Points:

• There have been limited data examining the safety and efficacy of transcatheter tricuspid repair systems.
• In the TRILUMINATE study, Tri-Clip was compared against medical therapy in patients with severe symptomatic TR.
• Tri-Clip implantation reduced severity of TR and improved quality of life. Tri-Clip was safe and resulted in only a 1.7% rate of major adverse events.

Continue reading →

Key Points:

• Mortality in high-risk PE remains unacceptably high (25%) despite advances in medical and interventional therapies.
• The FLAME study was a prospective, multi-center non-randomized observational study to describe the outcomes of patients undergoing mechanical thrombectomy and other modern therapies and generate evidence in high-risk PE. The primary outcome was a composite of all-cause mortality, bailout to alternate thrombus removal strategy, clinical deterioration, and major bleeding.
• Compared with a pre-established performance goal of 32%, patients treated with Flowtriever had a significant reduction in the primary endpoint. There was also significant reduction in in-hospital mortality (1.9% compared to 28.5%). There was no increase in adverse events in the FlowTriever group.
• Randomized evidence will be required to follow-up this observational study, but FlowTriever appears to be a safe, effective treatment which may reduce mortality in high-risk PE.

Continue reading →

Key Points:

• Indobufen, a platelet aggregation inhibitor, has been shown to be a shorter acting antiplatelet in comparison to aspirin. However, it has not been studied as a component of DAPT in patients requiring stent implantation.
• In the OPTION study, patients with CAD undergoing stent placement were randomized to either indobufen or aspirin. The primary outcome of interest was a 1-year composite of CV death, nonfatal MI, ischemic stroke, definite or probable stent thrombosis, or BARC type-2, 3, or 5 bleeding
• Indobufen was found to be non-inferior to aspirin in the primary endpoint.

Continue reading →

Key Points:

• There is substantial heterogeneity in the use of different non-invasive and invasive modalities for CAD risk stratification; however, there limited is RCT evidence dictating the optimal strategy.
• In the PRECISE study, patients with typical or atypical symptoms suggestive of potential CAD were randomized to either a risk-score based, “precision” strategy or usual care. The primary outcome of interest was a 1-year composite of death, nonfatal MI, or a coronary catheterization yielding no obstructive CAD.
• The precision strategy resulted in a significant 70% reduction in the primary outcome at 1 year compared to usual care.

Continue reading →