The following science will be presented at ACC.24 in Atlanta, GA, and was published online on March 25 in JACC, JACC: Basic to Translational Science, JACC: Case Reports, JACC: Heart Failure, JACC: Cardiovascular Interventions and JACC: Advances. Access all JACC Journals' simultaneous publications on the JACC Journals at ACC.24 page.

JACC

Markers to Stratify Disease Progression in ATTR-CA
A retrospective, multinational study by Adam Ioannou, MBBS, BSc, et al., focused on a large cohort of patients with transthyretin cardiac amyloidosis (ATTR-CA) showed that both an increase in N-terminal pro-B-type natriuretic peptide (NT-proBNP) and outpatient diuretic intensification (ODI) were significant markers of disease progression and were associated with an increased risk of mortality. In an editorial comment, Kevin M. Alexander, MD, FACC, wrote that "NT-proBNP progression and ODI are potential outcomes that are easy to measure yet yield robust prognostic information," and called them "strong candidates for adoption into clinical practice."

What is the Role of SGLT2is in ACHD?
In a retrospective study of adults with congenital heart disease (ACHD), Ralph M.L. Neijenhuis, MD, et al., found that treatment with SGLT2 inhibitors (SGLT2is) reduced the heart failure (HF) hospitalization rate by three-fold at six months, and "generally seem[s] safe, well-tolerated, and potentially beneficial in patients with [congenital HF]." In an editorial comment, Luke J. Burchill, MBBS, PhD; C. Charles Jain, MD; and William R. Miranda, MD, FACC, said that the study, based on data from four European ACHD centers, "represents progress in the nascent field of ACHD HF research."

REDUCE-IT Analysis: IPE CV Risk Reduction Across Lp(a) Levels
Through a post-hoc analysis of the REDUCE-IT trial, Michael Szarek, PhD, et al., found that icosapent ethyl (IPE) reduced risk for first and total major adverse cardiovascular events (MACE) among participants with cardiovascular disease or other risk factors. Furthermore, they found that baseline lipoprotein(a) (Lp[a]) levels were associated with MACE and that IPE reduced MACE across a range of Lp(a) levels. In an editorial comment, Michael J. Blaha, MD, MPH, and Harpreet S. Bhatia, MD, FACC, pointed out that, "Importantly, the reduction in risk with IPE did not vary by Lp(a) levels when assessed both continuously and using a threshold of 50 mg/dL" and that the study "adds to a growing body of literature that Lp(a) is closely associated with risk and should lead to further scrutiny of the arbitrary 50 mg/dL threshold."

What is the Natural History of AFMR?
In a retrospective study of patients with mild-moderate/moderate atrial function mitral regurgitation (AFMR), Jwan A. Naser, MBBS, et al., tracked the progression or regression of the disease, the incidence of left ventricular systolic dysfunction (LVSD) and associated mortality. The authors found that regression of MR was more common than progression, but that it was not associated with either an increase in LVSD risk or mortality over the two-year follow-up. Pieter M. Vandervoort, MD, and Sébastien Deferm, MD, PhD, write in an editorial comment that, "The lack of an independent association between progression/regression of AFMR and all-cause mortality once again supports the notion that comorbidities and the underlying LA myopathy are stronger prognostic drivers in this scenario."

PARAGON-HF Analysis: Sacubitril/Valsartan-Related Hypotension in Patients With HFpEF and HFmrEF
In a post-hoc analysis of the PARAGON-HF trial, Alberto Foà, MD, PhD, et al., found that among patients with HF with preserved or mildly reduced ejection fraction (HFpEF; HFmrEF), higher left ventricular ejection fraction (LVEF) was associated with risk of hypotension in patients treated with sacubitril/valsartan compared with valsartan only. Among the 13% of patients who experienced hypotension, there was a higher risk of cardiovascular death and total HF hospitalizations. A graded effect was found, with an LVEF ≥60% more likely associated with treatment-related hypotension and less clinical benefit from sacubitril/valsartan. The authors concluded that patients with below-normal LVEF can benefit from sacubitril/valsartan, but that for those with high LVEF, the risks outweigh the benefits. In an editorial comment, Camilla Hage, PhD; Johan Sundström, MD, PhD; and Lars H. Lund, MD, wrote that the analysis "provides additional evidence that [HF] with normal [LVEF] is different from HF with below normal [LVEF]."

Uniform Rule-Out Cardiac Troponin Threshold Effective For Women and Men?
In a study of nearly 63,000 consecutive patients admitted to the emergency department (ED) with possible myocardial infarction (MI), a single uniform rule-out threshold using high-sensitivity cardiac troponin I <5 ng/dL identified more women than men who were at low risk, while a similar proportion of women and men at low risk were discharged from the ED. Of the some 9,000 low-risk patients discharged, <5 experienced an MI or cardiac death at 30 days. Using a sex-specific threshold they derived and validated, Ziwen Li, PhD, et al., found that in the same population it identified more women at low risk (four in 100) and fewer men (seven in 100) compared with the uniform rule-out threshold. The authors wrote that the uniform rule-out threshold was "safe and effective for both sexes," and added that "Sex-specific rule-out thresholds should be considered, but their impact on effectiveness and safety may be limited." In an editorial comment, Fred S. Apple, PhD, calls physicians to action, writing that "it's not too soon for clinicians to take the initiative, stop avoiding this issue, and carefully develop evidence to determine if the data supports sex-specific thresholds. This paper is a good start to this endeavor."

NODE-303: Novel Etripamil Nasal Spray Safe, Effective For Recurrent PSVT
The open-label NODE-303 study found that self-administered intranasal etripamil, a novel agent, was safe and effective to use in a medically unsupervised setting for multiple episodes of AV nodal-dependent paroxysmal supraventricular tachycardia (PSVT). James E. Ip, MD, et al., reported that for all PSVT episodes in this real-world study, the rate of conversion was 69.9% by 60 minutes after administering the drug, with a mean time-to-conversation of 17 minutes. They wrote that the efficacy of etripamil was similar to that found in the double-blinded RAPID study.

DAPA-HF Analysis: Dapagliflozin Associated With Better Health Status in HFrEF
Among patients with HF with reduced ejection fraction (HFrEF), dapagliflozin, vs. placebo, reduced total time lost due to death, hospitalizations and impaired well-being at 360 days. Toru Kondo, MD, et al., wrote that the new patient-focused "integrated endpoints used in this study give a much more holistic patient-centered assessment of any treatment, reflecting also the health economic and societal perspective than traditional endpoints." Read the full study.

CLEAR Outcomes Analysis: Hispanic/Latinx Patients Receive Same Benefit With Bempedoic Acid
A prespecified exploratory subgroup analysis of the CLEAR Outcomes trial found that bempedoic acid was well tolerated and reduced cardiovascular events in Hispanic/Latinx participants, similar with those who were not. All study participants were statin intolerant. Fatima Rodriguez, MD, MPH, FACC, et al., wrote that Hispanic/Latinx patients are less likely to be prescribed statins yet have a high prevalence of dyslipidemia and increased cardiovascular risk. They conclude that bempedoic acid could be an effective nonstatin alternative for both Hispanic/Latinx and non-Hispanic/Latinx populations.

JACC: Basic to Translational Science

Diabetes, Renal Function Impair Clopidogrel-Mediated P2Y12 Inhibition
A prospective ex vivo and in vitro pharmacodynamic/pharmacokinetic investigation by Luis Ortega-Paz, MD, PhD, et al., found that patients with stable ischemic heart disease and diabetes mellitus (DM) treated with clopidogrel had impaired clopidogrel-mediated platelet P2Y12 inhibition, exacerbated by chronic kidney disease. Impaired renal function in these patients with DM was also associated with increased maximum platelet aggregation.

JACC: Case Reports

Severe Systolic Anterior Motion Revealed Post Mitral Valve Repair
Michel Chedid El Helou, MD, MsC, et al., reviewed a case of a 38-year-old man who presented with recurrent dyspnea and chest discomfort during exertion that started shortly after a mitral valve repair surgery. Transesophageal echocardiogram during a reoperation unmasked severe systolic anterior motion and torrential mitral regurgitation. The case, according to the authors, "Highlights the importance of careful pre-operative imaging and surgical planning in patients with mitral valve disease."

JACC: Heart Failure

HF Risk Among African American Women With an ICAM1 Missense Variant
A new study by Prarthana J. Dalal, MD, PhD, et al., traces the occurrence of an intercellular adhesion molecule-1 (ICAM1) variant (rs5491; p.K56M) across an age range of African American women. Results show that the variant, common in African Americans, is associated with HFpEF in African American women ≥70 years old.

Most Patients With New HFrEF Still Not Getting Quadruple Medical Therapy
By analyzing the Get With the Guidelines – Heart Failure registry, Stephen J. Greene, MD, FACC, et al., found that, while 82% of patients newly diagnosed with HFrEF were eligible for quadruple (ARNI, beta-blocker, mineralocorticoid receptor antagonist and SGLT2i) therapy, only 15.3% were actually prescribed it. Using clinical trial relative risk reductions, Greene, et al., concluded that the therapy fully realized could "yield large absolute reductions in mortality."

JACC: Cardiovascular Interventions

What Are National Trends and Outcomes of Acute MI Post TAVR?
In a large, national, retrospective data study using the Vizient database, Tanush Gupta, MD, FACC, et al., examined the incidence of STEMI and NSTEMI in patients who underwent TAVR. The study found it was infrequent, but NSTEMI was more common than STEMI (229 events per 100,000 person-years vs. 25 events per 100,000 person-years, respectively). Use of coronary revascularization was similar between TAVR patients and non-TAVR patients for STEMI (65.3% vs. 63.9%, respectively) and NSTEMI (41.4% vs. 41.7%) patients. In STEMI patients, in-hospital mortality was more common for TAVR patients than non-TAVR patients; the opposite was true in NSTEMI patients. David J. Cohen, MD, MSc, and Wally Omar, MD, FACC, wrote in an editorial comment that these results "adds important new information to our understanding of 'life after TAVR.'"

JACC: Advances

Hypertriglyceridemia and Multi-Organ Disease Among US Adults
Chen Gurevitz, MD, et al., analyzed data from the U.S. National Health and Nutrition Examination Survey to estimate the prevalence of chronic conditions and multi-organ disease in U.S. adults with severe hypertriglyceridemia (defined as serum triglycerides ³500 mg/dL) compared to those with moderate hypertriglyceridemia (200 to <500 mg/dL) and normal levels (<200 mg/dL). They found that chronic conditions and multi-organ disease were more common in those with higher triglyceride levels.