[Posted 26/Nov/2024]

AUDIENCE: Cardiology, Emergency Medicine

ACTION: The U.S. Food and Drug Administration has approved Attruby (acoramidis) to treat adults with cardiomyopathy (disorder that affects heart muscle) of wild-type or variant (hereditary) transthyretin-mediated amyloidosis (ATTR-CM) to reduce death and hospitalization related to heart problems.

Attruby is taken orally, twice daily. Recommended dosing is available in the prescribing information.

DISEASE OR CONDITION: ATTR-CM is a rare and serious disease that affects the heart muscle. In patients with ATTR-CM, there is a build-up of protein deposits in the heart, causing the walls of the heart to become stiff, and making the left ventricle unable to properly relax and fill with blood (called cardiomyopathy). As the condition progresses, the heart can become unable to pump blood out adequately, causing heart failure.

There are two types of ATTR-CM, hereditary ATTR-CM (hATTR-CM) and wild-type ATTR-CM (wATTR-CM). In hATTR-CM, which can run in families, there’s a variant in the transthyretin gene, which results in protein deposits in the heart. In wATTR-CM, there is no variant in the transthyretin gene.

While the true prevalence of ATTR-CM is unknown, increasing awareness and enhanced diagnostic tools have led to increasing estimates of the number of patients with ATTR-CM.

EFFECTIVENESS: The efficacy and safety of Attruby were evaluated in a multicenter, international, randomized, double-blind, placebo-controlled study in 611 adult patients with wild-type or hereditary (variant) ATTR-CM (NCT03860935).

The primary endpoint of the study included all-cause mortality and cumulative frequency of cardiovascular-related hospitalizations (CVH) over 30 months. At 30 months, more patients taking Attruby vs placebo were alive (81% vs 74%) and there were fewer CVH in those taking Attruby vs placebo (mean number of 0.3 vs 0.6 per year).

SAFETY INFORMATION: The most common adverse reactions were diarrhea and upper abdominal pain. Most of these gastrointestinal adverse reactions were categorized as mild and resolved without drug discontinuation.

DESIGNATIONS: Attruby received orphan drug designation for this indication.

Source: FDA Approves Drug for Heart Disorder Caused by Transthyretin-Mediated Amyloidosis. FDA. Published: November 25, 2024.

A Systematic Review

[Posted 24/Apr/2025]

AUDIENCE: Family Medicine, Cardiology

KEY FINDINGS: The use of cPOCUS by non-expert physicians after a short training course appears to be an accurate complementary tool for LVEF assessment in daily practice. Its diffusion in primary care could optimize patient management, without replacing specialist assessment.

BACKGROUND: Heart failure (HF) is the most frequent cardiovascular pathology in primary care. Echocardiography is the gold standard for diagnosis, follow-up, and prognosis of HF. Point-of-care ultrasound (POCUS) is of growing interest in daily practice. This study aimed to systematically review the literature to evaluate left ventricular ejection fraction (LVEF) assessment of unselected patients in primary care by non-expert physicians with cardiac POCUS (cPOCUS).

DETAILS: Authors searched in Medline, Embase, and Pubmed up to January 2024 for interventional and non-interventional studies assessing LVEF with cPOCUS in unselected patients with suspected or diagnosed HF in hospital or outpatient settings, performed by non-expert physicians. Forty-two studies were included, involving 6598 patients, of whom 60.2% were outpatients. LVEF was assessed by 351 non-expert physicians after an initial ultrasound training course. The LVEF was mainly assessed by visual estimation (90.2%). The most frequent views were parasternal long/short axis, and apical 4-chamber. The median time of cPOCUS was 8 minutes. A strong agreement was found (κ = 0.72 [0.63; 0.83]) compared to experts when using different types of ultrasound devices (hand-held and standard), and agreement was excellent (κ = 0.84 [0.71; 0.89]) with the same device. Training course combined a median of 4.5 hours for theory and 25 cPOCUS for practice.

Copyright © Oxford University Press. All rights reserved.

Source: Allimant, P., Guillo, L., Fierling, T., et al. (20245). Point-of-Care Ultrasound to Assess Left Ventricular Ejection Fraction in Heart Failure in Unselected Patients in Primary Care: A Systematic Review. Family Practice. 2025; 42(2): cmae040. Published: April, 2025. DOI: 10.1093/fampra/cmae040.

National Cohort and Co-Sibling Study

[Posted 21/Apr/2025]

AUDIENCE: Cardiology, Ob/Gyn

KEY FINDINGS: In this large national cohort, women who experienced any of 5 major adverse pregnancy outcomes had increased risk for HF up to 46 years later. Women with adverse pregnancy outcomes need early preventive actions and long-term clinical care to reduce the risk of HF.

BACKGROUND: Adverse pregnancy outcomes, such as preterm delivery and hypertensive disorders of pregnancy, may be associated with higher future risks of heart failure (HF). However, the comparative effects of different adverse pregnancy outcomes on long-term risk of HF, and their potential causality, are unclear. The authors sought to examine 5 major adverse pregnancy outcomes in relation to long-term risk of HF in a large population-based cohort.

DETAILS: A national cohort study was conducted of all 2,201,638 women with a singleton delivery in Sweden in 1973-2015, followed up for HF identified from nationwide outpatient and inpatient diagnoses through 2018. Cox regression was used to compute HRs for HF associated with preterm delivery, small for gestational age, preeclampsia, other hypertensive disorders of pregnancy, and gestational diabetes, while adjusting for other adverse pregnancy outcomes and maternal factors. Co-sibling analyses assessed for potential confounding by shared familial (genetic or environmental) factors. In 48 million person-years of follow-up, 667,774 women (30%) experienced an adverse pregnancy outcome, and 19,922 women (0.9%) were diagnosed with HF (median age, 61 years). All 5 adverse pregnancy outcomes were independently associated with long-term increased risk of HF. With up to 46 years of follow-up after delivery, adjusted HRs for HF associated with specific adverse pregnancy outcomes were: gestational diabetes, 2.19 (95% CI: 1.95-2.45); preterm delivery, 1.68 (95% CI: 1.61-1.75); other hypertensive disorders, 1.68 (95% CI: 1.48-1.90); preeclampsia, 1.59 (95% CI: 1.53-1.66); and small for gestational age, 1.35 (95% CI: 1.31-1.40). All HRs remained significantly elevated (1.3- to 3.0-fold) even 30 to 46 years after delivery. These findings were only partially explained by shared familial factors. Women with multiple adverse pregnancy outcomes had further increases in risk (eg, up to 46 years after delivery, adjusted HRs associated with 1, 2, or ≥3 adverse pregnancy outcomes were 1.51 [95% CI: 1.47-1.56], 2.31 [95% CI: 2.19-2.45], and 3.18 [95% CI: 2.85-3.56], respectively).

Copyright © American College of Cardiology Foundation. All rights reserved.

Source: Crump, C., Crump, J., and Crump, K. (20245). Adverse Pregnancy Outcomes and Long-Term Risk of Heart Failure in Women: National Cohort and Co-Sibling Study. J Am Coll Cardiol HF.. 2025; 3(4): 589–598. Published: April, 2025. DOI: 10.1016/j.jchf.2024.11.004.

A Population-Based Cohort Study in Sweden

[Posted 3/Mar/2025]

AUDIENCE: Cardiology, Emergency Medicine, Rheumatology

KEY FINDINGS: In patients with gout and without CHD, long-term allopurinol use protects against first-ever ACS compared with non-users. In contrast, allopurinol initiators, possibly having more systemic inflammation, had a higher risk of first-ever ACS compared with long-term users.

BACKGROUND: Purpose of this study is to investigate the impact of allopurinol use on the risk of first-ever acute coronary syndrome (ACS) event in patients with gout.

DETAILS: Using national and regional register data, we included all patients with a gout diagnosis at primary or specialised care in Western Sweden in the period 2007-2017 (n=18,862; 67% male patients). Patients with a prior history of coronary heart disease (CHD) were excluded. Follow-up started at the first gout diagnosis and ended at the first-ever ACS event, death or study end. The main outcome was the risk of first-ever ACS in: (1) allopurinol users versus non-users, by defining three categories of allopurinol exposure: exposed to 100 mg, >100 mg and no exposure (reference) and (2) allopurinol initiators (within 125 days) versus long-term users (reference). Multivariable logistic regression analysis was used to calculate ORs and 95% CIs. In analysis 1 (n=18,862), 15.3% (n=2892) were exposed to 100 mg, 9.1% (n=1717) to >100 mg and 75.6% (n=14,253) were not exposed. Allopurinol users were older and had more comorbidities compared with non-users. Allopurinol exposure (100 mg and >100 mg) was associated with significantly lower odds of first-ever ACS (OR 0.77; 95% CI 0.63 to 0.94, and OR 0.61; 95% CI 0.47 to 0.81, respectively). In Analysis 2, allopurinol initiators (n=489) had significantly higher odds of first-ever ACS compared with long-term users (n=2916) (OR 1.68; 95% CI 1.03 to 2.75).

Copyright © BMJ Publishing Group Ltd.. All rights reserved.

Source: Drivelegka, P., Jacobsson, L., Sandstrom, T. Z., et al. (2025). Allopurinol Use and Risk of Acute Coronary Syndrome in Gout Patients: A Population-Based Cohort Study in Sweden. BMJ Open. 2025; 15(2): e092522. Published: February 27, 2025. DOI: 10.1136/bmjopen-2024-092522.

Primary Results of the PEERLESS Randomized Controlled Trial

[Posted 4/Feb/2025]

AUDIENCE: Cardiology, Emergency Medicine

KEY FINDINGS: PEERLESS met its primary end point in favor of LBMT compared with CDT in treatment of intermediate-risk pulmonary embolism. LBMT had lower rates of clinical deterioration and/or bailout and postprocedural intensive care unit use compared with CDT, with no difference in mortality or bleeding.

BACKGROUND: There are a lack of randomized controlled trial data comparing outcomes of different catheter-based interventions for intermediate-risk pulmonary embolism.

DETAILS: PEERLESS is a prospective, multicenter, randomized controlled trial that enrolled 550 patients with intermediate-risk pulmonary embolism with right ventricular dilatation and additional clinical risk factors randomized 1:1 to treatment with large-bore mechanical thrombectomy (LBMT) or catheter-directed thrombolysis (CDT). The primary end point was a hierarchal win ratio composite of the following (assessed at the sooner of hospital discharge or 7 days after the procedure): (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) postprocedural intensive care unit admission and length of stay. Assessments at the 24-hour visit included respiratory rate, modified Medical Research Council dyspnea score, New York Heart Association classification, right ventricle/left ventricle ratio reduction, and right ventricular function. End points through 30 days included total hospital stay, all-cause readmission, and all-cause mortality. The primary end point occurred significantly less frequently with LBMT compared with CDT (win ratio, 5.01 [95% CI, 3.68-6.97]; P<0.001). There were significantly fewer episodes of clinical deterioration and/or bailout (1.8% versus 5.4%; P=0.04) with LBMT compared with CDT and less postprocedural intensive care unit use (P<0.001), including admissions (41.6% versus 98.6%) and stays >24 hours (19.3% versus 64.5%). There were no significant differences in mortality, intracranial hemorrhage, or major bleeding between strategies or in a secondary win ratio end point including the first 4 components (win ratio, 1.34 [95% CI, 0.78-2.35]; P=0.30). At the 24-hour visit, respiratory rate was lower for patients treated with LBMT (18.3±3.3 versus 20.1±5.1; P<0.001), and fewer had moderate to severe modified Medical Research Council dyspnea scores (13.5% versus 26.4%; P<0.001), New York Heart Association classifications (16.3% versus 27.4%; P=0.002), and right ventricular dysfunction (42.1% versus 57.9%; P=0.004). Right ventricle/left ventricle ratio reduction was similar (0.32±0.24 versus 0.30±0.26; P=0.55). Patients treated with LBMT had shorter total hospital stays (4.5±2.8 overnights versus 5.3±3.9 overnights; P=0.002) and fewer all-cause readmissions (3.2% versus 7.9%; P=0.03), whereas 30-day mortality was similar (0.4% versus 0.8%; P=0.62).

Copyright © American Heart Association, Inc. All rights reserved.

Source: Jaber, W. A., Gonsalves, C. F., Stortecky, S., et al. (2024). Large-Bore Mechanical Thrombectomy Versus Catheter-Directed Thrombolysis in the Management of Intermediate-Risk Pulmonary Embolism: Primary Results of the PEERLESS Randomized Controlled Trial. Circulation. 2025; 151(5). Published: February 4, 2025. DOI: 10.1161/CIRCULATIONAHA.124.07236.

[Posted 2/Sep/2024]

AUDIENCE: Internal Medicine, Nursing

KEY FINDINGS: Scientists from the University of Copenhagen have detected lipid biomarkers in children and teenagers with obesity that indicate an increased risk of developing type 2 diabetes, liver and heart disease as adults. A one-year lifestyle intervention lowered the levels of these lipid biomarkers, which demonstrates the importance of early intervention for children with obesity.

BACKGROUND: The number of children and teens with obesity is increasing worldwide, with over 250 million expected to be affected by 2030. It is a major public health crisis, as children with obesity risk developing insulin resistance, fatty liver, and high blood pressure, which may lead to diseases such as cardiovascular disease, type 2 diabetes and liver disease, later in life.

DETAILS: Scientists think these diseases can be triggered by changes in the body's lipids -- a wide range of fats and oils in the body including triglycerides and cholesterol that serve many purposes including energy storage and cellular signalling. But it is still not well understood how lipid species change in children with obesity, and how they are linked to early cardiometabolic complications.

Now, scientists at the University of Copenhagen have discovered that lipid species linked to cardiometabolic disease in adults are strongly associated with cardiometabolic risk factors in children and teenagers with obesity. The findings could pave the way for tests that serve as an early warning system for cardiometabolic disease.

"Our study shows that the impact of cardiometabolic associated lipid species emerges early in life in children with obesity, particularly affecting liver function and glucose metabolism. These risk lipid species could potentially be explored further as biomarkers for diagnosing or predicting cardiometabolic risk in children at high risk, offering new insights for early detection and intervention," says Postdoc Yun Huang from the Novo Nordisk Foundation Center for Basic Metabolic Research at the University of Copenhagen, and co-first author of the study in Nature Medicine.

Early intervention reverses cardiometabolic disease risk

The scientists made their discoveries by drawing on the HOLBAEK Study biobank of more than 4,000 children with and without obesity. at the Children's Obesity Clinic at Holbaek Hospital. Together with scientists at Steno Diabetes Center Copenhagen, they harnessed powerful mass spectrometry technology to map hundreds of individual lipid species, each with distinct structures and functions, providing a detailed picture of lipid metabolism. By analyzing the differences in the lipid profiles of 958 children with overweight or obesity and 373 who had normal weight, they gained deep insight into obesity altered lipid profiles and their link to cardiometabolic risk, and the ability to detect excessive fat in the liver.

Copyright © ScienceDaily or by other parties, where indicated. All rights reserved.

Source: University of Copenhagen - The Faculty of Health and Medical Sciences (2024). A Simple Blood Test Warns of Possible Cardiometabolic Complications for Children With Obesity. ScienceDaily. 2024; Published: September 20, 2024. DOI: 10.1038/s41591-024-03279-x.