Key Points:

• In the GIPS-IV study, patients with STEMI were randomized to either receiving sodium thiosulfate (STS), an emerging therapy targeting infarct size, or placebo. The outcomes of interest included infarct size as measured by CMR, LVEF, peak CK-MB, NT pro-BNP, and clinical events (ie, MACE, recurrent STEMI, CV mortality) at 4 months. The presence of adverse safety events was also observed.
• Treatment with STS did not result in significant improvement in either the primary or secondary outcomes. STS administration was safe, with an increased risk of nausea and vomiting as the primary side effect.

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Key Points:

• In the original CANTOS, patients with stable CAD post-MI with elevated CRP were randomized to either canakinumab or placebo. In this secondary analysis, , the relative contributions of residual cholesterol risk and residual inflammatory risk were determined in the prediction of MACE, CV death, and mortality in patients already treated with statins, which was then stratified by eGFR.
• Elevated levels of both hsCRP and IL-6 were found to be predictive of MACE in patients with both preserved and reduced kidney function; however, LDLC and non-HDLC were predictive of MACE only in preserved kidney function. Elevated CRP predicted CV mortality, with or without kidney dysfunction.
• Residual inflammatory risk appears to play an important role in determining MACE risk in patients already treated with lipid-lowering therapy.

Inflammation has recently been identified as an independent contributor to the development of atherosclerotic cardiovascular disease, and it has also been theorized to act jointly with hyperlipidemia in the development of this risk. Canakinumab is a monoclonal antibody which neutralizes IL-1β and was recently studied in the CANTOS trial to determine whether it could effect MACE reduction in patients with stable CAD post MI and elevated CRP. In a breaking presentation at the 2022 American College of Cardiology Conference today, Dr. Paul Ridker (Brigham and Women’s Hospital, Boston) and his team presented “Residual Inflammatory Risk and Residual Cholesterol Risk Among Statin Treated Atherosclerosis Patients With and Without Chronic Kidney Disease: A Secondary Analysis of CANTOS.”

The original CANTOS study (NCT01327846) was a randomized multicenter trial which demonstrated that patients with stable CAD post MI and elevated CRP (≥2mg/L) led to reduced MACE at a median follow-up of 3.7 years. In this secondary analysis, the relative contributions of residual cholesterol risk and residual inflammatory risk were determined in the prediction of MACE, CV death, and mortality, which was then stratified by eGFR.

A total of 9,151 randomized patients (all of whom were treated with statins) were analyzed and followed for up to 5 years. hsCRP, IL-6, LDLC, and non-HDLC were measured and monitored. For the primary outcome, hsCRP and IL-6 were both found to be predictive of MACE in patients with both preserved and reduced kidney function; however, LDLC and non-HDLC were predictive of MACE only in preserved kidney function. Elevated CRP predicted CV mortality, with or without the concomitant presence of kidney dysfunction.

When discussing the additive potential of anti-inflammatory therapies to existing medical therapy for CAD at the ACC, Dr. Ridker stated: “Relative risk reduction is infinite…there is a lot of residual risk in these [stable CAD] patients…upcoming trials of anti-inflammatory drugs will be in addition to standard of care therapies for CAD [such as SGLT2s].”

Key Points

• Prompt and complete removal of CIED systems is strongly recommended by all major professional societies, however only 1 in 5 patients with CIED infection undergo prompt extraction (<6 days after infection) in a nationally-representative Medicare cohort.
• Compared to extraction, no extraction is associated with a significantly higher risk-adjusted 1-year mortality rate (HR 0.73, 95% CI 0.70-0.81).
• Regionalization of care and creation of regional health system pathways may promote cooperation between extraction centers and referral centers, to increase extraction rates and improve morbidity and mortality for patients with CIEDs.

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Key Points:

• As transcatheter aortic valve replacement (TAVR) has experienced expanded indications into patients with low and intermediate surgical risk, conversations about valve durability have become increasingly important.
• Analysis of the pivotal CoreValve and SURTAVI trials demonstrated that TAVR was associated with less structural valve deterioration at 5 years than bioprosthetic SAVR.
• The analysis furthermore showed that structural valve deterioration was associated with higher risk of all cause mortality, including cardiovascular mortality and hospitalization for aortic valve disease.

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Key Points

• Tricuspid regurgitation is a debilitating valve disorder characterized by shortness of breath, fatigue, and recurrent hospitalization for fluid retention.
• The PASCAL device (Edwards Life Sciences) is a transcatheter edge-to-edge clip that is used to perform tricuspid valve repair.
• The CLASP-TR study is a single-arm trial enrolling patients with severe tricuspid regurgitation to receive transcatheter edge to edge repair with the PASCAL device.
• At one year, in patients who remained alive, all patients had at least a one-grade improvement in their tricuspid regurgitation, with 75% having maintained an improvement of at least two grades.

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Key Points

• While VT ablation has been associated with improved survival, the most ideal time to undergo VT ablation remains undefined.
• PARTITA was the first clinical trial to randomize patients to early VT ablation versus standard of care after ICD implant for both ischemic and non-ischemic cardiomyopathy.
• Despite its small sample size (n=56), the adaptive Bayesian design of this study predicted a 99.9% predictive probability of success, causing early termination of the trial. Early VT ablation caused a statistically significant reduction in the primary outcome of all-cause mortality or worsening heart failure, compared to standard of care (4.3% vs 41.7%, p=0.01).
• Furthermore, ATP termination of VT was found to be the most significant predictor of subsequent ICD shocks, which suggests that it may be beneficial to perform VT ablation even earlier after ICD implant.

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Key Points

• Optimal medical therapy for patients with Heart Failure with Reduced Ejection Fraction (HFrEF) compromises of renin-angiotensin-aldosterone-system inhibitors that often cause hyperkalemia.
• If hyperkalemia cannot be mitigated with alternative methods, dose reductions, which compromise the effect of the optimal therapies, are often employed.
• Patirometer, which binds to potassium in exchange for calcium, was shown to help mitigate hyperkalemia in patients with HFrEF on RAAS-i.

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Key Points

• Selective XIa inhibitor Asundexian may innovate the field of oral anticoagulation by finally uncoupling hemostasis from thrombosis and potentially allowing similar protection from thromboembolic events without increasing bleeding risk among patients with atrial fibrillation.
• The Phase 2 dose-finding PACIFIC-AF trial (n=755) compared Asundexian 20 mg, Asundexian 50 mg and apixaban among patients with atrial fibrillation followed for 14 weeks. While Asundexian 50 mg showed a significant reduction in major and non-major clinically relevant bleeding, the low bleeding rate and resulting wide confidence intervals suggests more data are needed to better understand the comparative effectiveness and safety of this novel agent versus DOACs.

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Key Points

• PCSK-9 inhibitors have emerged as a viable treatment option patients hypercholesterolemia despite adequate tolerance of statin therapies.
• The role of thin capped fibrous atheromas with a lipid rich pool in causing myocardial infarction is well described, but the effect of PCSK-9 inhibitors on these plaques is yet to be explored
• PACMAN-AMI randomized patients presenting with acute myocardial infarction to receive alirocumab, a PCSK-9 inhibitor, or placebo in addition to high intensity statin. At baseline and 52 weeks, coronary imaging was performed with the use of intravascular ultrasound and optical coherence tomography to assess changes in plaque burden.
• At 52 weeks, there was a substantial improvement in overall plaque volume, and thickening of fibrous atheroma caps, suggesting alirocumab confers protection from myocardial infarction.

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Key Points:

• In the EXPLORER-LTE study, patients with severely symptomatic obstructive HCM previously enrolled in the EXPLORER-HCM study underwent ongoing therapy with mavacamten. The outcomes of interest included changes in resting and Valsalva LVOT gradient, functional class, LVEF, and reduction in BNP. The presence of adverse safety events was also monitored.
• Treatment with mavacamten led to a reduction in resting and Valsalva LVOT at 84 weeks, as well as symptomatic improvement at 48 weeks. There was a concomitant reduction in BNP as well as an expected mild decrease in LVEF. No new safety events were observed.

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Key Points:

• A need for various lipid-lowering agents to combat high cholesterol exists for those already taking statin medications.
• Vupanorsen is a monoclonal antibody that inhibits lipoprotein lipase and has been shown to decrease non-HDL cholesterol in phase II trias.
• In this phase III trial, vupanorsen was found to reduce non-HDL cholesterol by up to 28% in patients who were already taking a statin medication, however was associated with injection site reactions and elevated liver enzymes at higher doses.

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Key Points:

• In the Phase I APOLLO study, patients without known ASCVD and elevated Lp(a) ≥150nmol/L were treated with a novel siRNA therapy (SLN360) in a single ascending dose study. The primary outcome was degree of Lp(a) reduction at 150 days. Secondary outcomes included assessment of changes in LDL-C, apoB, oxidized LDL, inflammatory markers, plasminogen, and pharmacokinetics.
• Treatment with SLN360 resulted in a persistent 70-80% reduction in Lp(a) at 150 days in the higher dose regimens (300 and 600mg). A 20-30% reduction in LDL-C and apoB was also observed. Further trials are warranted to determine the effect of a multi-dose regimen as well as to determine potential impact on the development of ASCVD.

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Key Points

• PCI has yet to be shown to be superior to CABG with respect to quality of life and angina in those with multivessel coronary artery disease.
• This substudy of the FAME-3 trial, which randomized participants to FFR-guided PCI versus CABG, sought to understand whether physiology-guided PCI would have an effect on quality of life and angina.
• Quality of Life was assessed by the EQ-5D questionnaire, and angina was assessed on the Canadian Coronary Symptoms scale.
• At 1 year, there were no differences in angina and quality of life between those who underwent FFR-guided PCI and those who underwent CABG.

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Key Points:

• In the EDIT-CMD study, patients with coronary vasomotor dysfunction (encompassing both coronary vasospasm and microvascular dysfunction, as defined by coronary function testing) were treated with either diltiazem or placebo. The primary outcome was resolution of either vasospasm or microvascular dysfunction on repeat coronary function testing after 6 weeks of treatment. Secondary outcomes included reduction in coronary flow reserve, index of microvascular resistance, flow at rest and hyperemia, and symptoms of angina/quality of life.
• Treatment with diltiazem resulted in reduced epicardial spasm (on an underpowered secondary analysis) but had no effect on the primary outcome (resolution of either spasm or microvascular dysfunction), anginal symptoms, or quality of life. There was a small significant reduction in coronary flow reserve with diltiazem as well.

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Key Points

• The COMPLETE trial, published in 2019, demonstrated that in patients with ST-segment elevation myocardial infarction found to have multivessel disease, complete revascularization was superior to culprit-only revascularization in reducing the risk of cardiovascular death or subsequent myocardial infarction.
• In this secondary analysis of the COMPLETE trial, the authors sought to understand the effect of both treatment modalities (complete or culprit-only) on patients’ perceptions of angina-related quality of life.
• Seattle Angina Questionnaires were administered at baseline, 3 months, 6 months, and 3 years.
• There was no significant difference in angina-related quality of life for patients who underwent complete revascularization or culprit-only percutaneous coronary intervention. Both groups demonstrated significant improvement in Seattle Angina Questionnaire scores

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Key points:

• Sodium-HF sought to determine whether dietary sodium reduction reduces the morbidity or mortality associated with heart failure (HF) in the largest randomized trial testing dietary sodium in HF patients to date
• Dietary sodium reduction (to a target of <1500 mg/day) in HF patients did not reduce the clinical composite outcome of all-cause mortality, cardiovascular-related hospitalization, or cardiovascular-related emergency department visits compared with usual care over 12 months
• NYHA functional class and KCCQ scores were modestly improved in low sodium vs. usual care groups, indicating signal for better quality of life in those patients adhering to sodium restricted diets
• Investigators conclude that clinicians and patients should consider a dietary intervention similar to other medical therapies and balance the potential benefits on an individual basis

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Key Points: 

• Tranexamic acid, given to patients undergoing noncardiac surgery, was associated with fewer bleeding events at 30 days.

• Participants of the POISE-3, a multinational, double-blinded randomized control study,  were randomized to receive IV tranexamic acid or placebo during surgery.

• Study investigators conclude that the drug, already in widespread use for cardiac surgery, could have major economical and public health impact if used in the noncardiac space.

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Key Points:

• • In the VALOR-HCM study, patients with severely symptomatic obstructive HCM on maximally tolerated medical therapy were treated with either mavacamten (a novel cardiac myosin inhibitor) or placebo. The primary outcome was composite of patient decision to proceed with SRT or continue to meet 2011 ACC/AHA guideline eligibility for SRT after 16 weeks. Pre-specified secondary analyses included a) change in post-exercise LVOT gradient, b) number of patients with a ≥1 class of NYHA improvement, c) change in KCCQ clinical summary score, d) change in NT-proBNP, and e) change in Troponin I.
  • Treatment with mavacamten reduced the primary endpoint, which was largely driven by guideline eligibility for SRT 17.9% of patients were eligible for SRT therapy at 16 weeks in the mavacamten arm, compared to 76.8% in the placebo arm. Mavacamten also led to a reduction in resting and Valsalva LVOT gradient, troponin and BNP, and KCCQ score.

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