[Posted 12/Oct/2026]

AUDIENCE: Cardiology, Endocrinology, Internal Medicine

KEY FINDINGS: This study found that HF was associated with increased visceral adiposity, reduced muscle volume, and greater muscle fat infiltration, even when patients were compared with controls matched for BMI. The differing patterns across HF phenotypes suggest that body composition abnormalities are not uniform among patients with heart failure.

The findings indicate that BMI and conventional anthropometric measures may underestimate clinically relevant metabolic and muscular abnormalities. Advanced imaging and more consistent definitions of sarcopenia may improve characterization of these abnormalities, although further research is needed to determine their prognostic value and implications for treatment.

BACKGROUND: Heart failure (HF) is associated with metabolic and musculoskeletal abnormalities that may not be adequately captured by body mass index (BMI). Excess visceral fat, reduced skeletal muscle volume, and increased fat infiltration within muscle can coexist and may differ across HF phenotypes. This study used advanced imaging to characterize body composition in patients with HF compared with matched controls and to examine differences among HF with reduced ejection fraction (HFrEF), mildly reduced ejection fraction (HFmrEF), and preserved ejection fraction (HFpEF).

DETAILS: Researchers analyzed participants in the UK Biobank Imaging Study. A total of 185 individuals with HF and available ejection fraction measurements were matched in a 1:5 ratio with 925 controls matched for age, sex, and BMI. Whole-body magnetic resonance imaging (MRI) was used to quantify visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue, liver fat, thigh fat-free muscle volume, and muscle fat infiltration (MFI). Dual-energy x-ray absorptiometry (DXA) was used to measure total fat and appendicular lean mass. Personalized z-scores adjusted for sex and body size were calculated. Adverse muscle composition (AMC) was defined by the combination of low muscle volume and high muscle fat infiltration. The investigators also assessed sarcopenia using grip strength and DXA-derived lean mass criteria.

Compared with matched controls, participants with HF had significantly greater visceral adipose tissue (z-score, 0.46 ± 1.1 vs 0.07 ± 1.0; P < 0.001) and muscle fat infiltration (8.4% ± 2.3% vs 7.6% ± 2.0%; P < 0.001). Adverse muscle composition was present in 36% of participants with HF compared with 17% of controls (P < 0.001). Muscle volume was also lower in the HF group (z-score, −0.7 ± 1.0 vs −0.1 ± 0.9; P < 0.001). Body composition patterns differed across HF phenotypes. HFmrEF was associated with the highest visceral adipose tissue levels and lowest muscle volume. HFpEF showed greater overall fat and muscle fat infiltration, whereas HFrEF had the highest prevalence of adverse muscle composition and the weakest grip strength.

Despite the MRI-detected muscle abnormalities, the estimated prevalence of sarcopenia varied considerably according to the diagnostic criteria applied, highlighting inconsistencies among current definitions.

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Source: Butler, J., Fioretti, F., Anker, S. D., et al. Body Composition in Heart Failure: A Magnetic Resonance Imaging and Dual X-Ray Absorptiometry Assessment in the UK Biobank Study. JACC: Heart Failure. 2026; 14(10): 103242. Published: October, 2026. DOI: 10.1016/j.jchf.2026.103242.

A Paradigm for Healthy Aging

[Posted 6/Oct/2026]

AUDIENCE: Ob/Gyn, Endocrinology, Internal Medicine

KEY FINDINGS: Key Information The FIGO-IMS position paper reframes hormone therapy in POI and early menopause as replacement of prematurely lost ovarian hormones, with potential implications for healthy aging. Treatment decisions should consider age at ovarian insufficiency, symptoms, bone health, cardiovascular risk, uterine status, reproductive goals, and individual contraindications.

The evidence supports a comprehensive, individualized approach rather than assuming that regimens used for typical-age menopause are sufficient for younger women with prolonged estrogen deficiency. The authors also acknowledge important evidence gaps, particularly regarding long-term cardiovascular outcomes and comparative effectiveness of different hormone regimens.

BACKGROUND: Premature ovarian insufficiency (POI) and early menopause are associated with prolonged estrogen deficiency during years when ovarian hormone production would ordinarily continue. Beyond vasomotor symptoms and reproductive consequences, estrogen deficiency may affect skeletal, cardiovascular, metabolic, cognitive, and genitourinary health. Hormone therapy (HT) has traditionally been considered primarily for symptom control, but its role in replacing deficient ovarian hormones and supporting long-term health warrants broader clinical consideration.

A joint position paper from FIGO and the International Menopause Society (IMS) reviews current evidence and proposes a more comprehensive approach to hormone therapy in women with POI or early menopause.

DETAILS: The position paper examines the physiological rationale for estrogen replacement, the timing and duration of treatment, hormone formulation and route of administration, and the potential implications for bone and cardiovascular health. It discusses the distinction between hormone replacement in younger women with premature estrogen loss and conventional menopausal hormone therapy initiated around the usual age of menopause. The authors review evidence supporting physiological estradiol replacement, including transdermal 17β-estradiol at 100 micrograms per day or oral 17β-estradiol at 2-4 mg per day. The paper also addresses the need for progestogen protection in women with an intact uterus, individualization of treatment, fertility considerations, and the limitations of available evidence concerning long-term cardiovascular outcomes and comparisons between HT and combined oral contraceptives.

The position paper emphasizes that hormone therapy in women with POI or early menopause should be considered an important component of long-term health management, rather than solely a treatment for vasomotor symptoms. Physiological estrogen replacement may help maintain bone mineral density and address consequences of premature estrogen deficiency. The authors discuss evidence that transdermal estradiol at 100 micrograms per day can restore lumbar spine and femoral neck bone mineral density to normal levels in women with POI. However, evidence regarding the superiority of higher estrogen doses for all skeletal outcomes remains inconsistent, and comparative data on major cardiovascular outcomes are limited.

The paper also highlights the need for further research comparing hormone therapy with combined oral contraceptives and evaluating long-term health outcomes, treatment acceptability, and optimal regimens.

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Source: Benedetto, C., Khadilkar, S. S., Nappi, R. E., et al. Hormone therapy (HT) in women with premature ovarian insufficiency or early menopause: Time to think of a new paradigm for healthy aging. Journal of Gynecology & Obstetrics.. 2026; 175(1): 26-47. Published: October, 2026. DOI: 10.1002/ijgo.71217.

[Posted 5/Oct/2026]

AUDIENCE: Family Medicine, Endocrinology, Primary Care

KEY FINDINGS: Among adults older than 50 years initiating levothyroxine, an initial dose exceeding 1.0 μg/kg per day was associated with higher long-term risks of cardiovascular events, bone outcomes, and all-cause mortality compared with lower initial dosing. The findings support careful consideration of initial dose and subsequent titration in older patients. However, the observational design does not establish that higher dosing directly caused these outcomes, and prospective studies are needed to validate the findings.

BACKGROUND: Levothyroxine is commonly prescribed for hypothyroidism, but determining an appropriate initial dose in older adults remains challenging. Both insufficient and excessive thyroid hormone replacement may adversely affect cardiovascular health, bone integrity, and survival. This study used an emulated target trial approach to evaluate the association between initial weight-based levothyroxine dosing and long-term clinical outcomes in adults older than 50 years.

DETAILS: This observational study used data from The Health Improvement Network, a UK primary care database, covering January 1, 2006, through December 31, 2021. Eligible participants were adults older than 50 years with diagnosed hypothyroidism, at least one recorded thyroid-stimulating hormone (TSH) measurement exceeding 4.0 mU/L, and a new levothyroxine prescription during the study period. The investigators compared patients initiating levothyroxine at more than 1.0 μg/kg per day with those receiving 1.0 μg/kg per day or less. Dosing was assessed using both total bodyweight and lean bodyweight. Participants were followed for up to 10 years for cardiovascular events, bone outcomes, and all-cause mortality. Inverse probability of treatment weighting was used to adjust for baseline confounders, and weighted Cox proportional hazards models were applied to estimate outcome associations.

A total of 19,027 records were eligible, including 14,296 women (75%) and 4,731 men (25%). The cardiovascular analysis included 15,463 adults, the bone health analysis included 14,947, and all 19,027 participants were included in the mortality analysis. Unweighted event rates were higher among patients initiating levothyroxine at more than 1.0 μg/kg per day than among those receiving lower doses. Cardiovascular events occurred in 20% versus 18%, bone outcomes in 13% versus 9%, and all-cause mortality in 18% versus 17%, respectively. Higher initial dosing was associated with increased risk of cardiovascular events (adjusted hazard ratio [HR], 1.18; 95% CI, 1.08-1.29), bone outcomes (HR, 1.29; 95% CI, 1.16-1.43), and all-cause mortality (HR, 1.17; 95% CI, 1.09-1.25).

Using total bodyweight-based dosing, the weighted 10-year absolute risk differences between the higher- and lower-dose groups were 1.3% (95% CI, 0.3-3.0) for cardiovascular events, 3.0% (95% CI, 1.6-4.5) for bone outcomes, and 3.4% (95% CI, 1.7-5.1) for all-cause mortality. Similar associations were observed in analyses using lean bodyweight-based dosing.

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Source: Holley, M., Wilkes, S., Moss, E. D., et al. Weight-based levothyroxine dosing and long-term cardiovascular, bone, and mortality outcomes in older adults: an emulated target trial using UK primary care data. The Lancet Primary Care. 2026; 2(8): 100194. Published: August, 2026. DOI: 10.1016/j.lanprc.2026.100194.

[Posted 25/Sep/2026]

AUDIENCE: Critical Care Nursing, Palliative Hospice Nursing

KEY FINDINGS: A structured, interprofessional approach to palliative ECMO de-escalation can reduce variability in end-of-life practice and support more consistent symptom management and communication. Incorporating patient and family preferences into the process, together with proactive symptom management and staff debriefing, was associated with a more comfortable and dignified end-of-life experience in this quality-improvement setting.

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is an invasive, potentially lifesaving therapy associated with complications involving multiple organ systems. When ECMO is no longer considered beneficial, de-escalation or decannulation may be required as part of a transition to comfort-focused care and natural death. At a tertiary care facility with 64 beds using ECMO, variability was identified in ECMO initiation, communication with patients and families, determination of nonbeneficial therapy, and symptom management during de-escalation.

DETAILS: This quality-improvement project integrated palliative care, reviewed existing literature on best practices, and established an interprofessional task force focused on ECMO de-escalation. New clinical guidelines were developed to provide a consistent, evidence-based framework for communication, decision-making, symptom management, and de-escalation/decannulation. The initiative was designed to reduce practice variability while improving the experience of patients, families, and clinicians during transition to comfort-directed care.

Implementation of the guidelines decreased practice variability and reduced patient and family stress and discomfort during ECMO de-escalation and decannulation. Team members reported decreases in symptoms of secondary trauma and moral distress associated with these situations. They also reported improved delivery of end-of-life care, including family education and support, patient advocacy, and symptom management. Family members valued greater attention to both patient and family well-being, while structured staff debriefings supported reflection and identification of opportunities for improvement.

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Source: Arbour, R., Abate, M., Garcia, O., et al. Palliative Extracorporeal Membrane Oxygenation Decannulation: An Ethical, Evidence-Based Approach. Critical Care Nurse. 2026; 46(4): 17-28. Published: August 1, 2026. DOI: 10.4037/ccn2026166.

[Posted 23/Sep/2026]

AUDIENCE: Cardiology, Oncology, Internal Medicine

KEY FINDINGS: In this large real-world cohort of patients with early-stage HER2-positive breast cancer, biosimilar trastuzumab use increased markedly between 2018 and 2024 without a statistically significant difference in heart failure risk compared with reference trastuzumab. Overall heart failure occurred in 5.9% of the study population. Comorbidity burden and older age were associated with higher heart failure risk, emphasizing the importance of cardiovascular risk assessment during HER2-directed therapy. Because this was a retrospective claims-based study, longer follow-up and additional real-world studies are needed to further evaluate long-term cardiac outcomes.

BACKGROUND: Trastuzumab is an important treatment for HER2-positive breast cancer, but cardiac dysfunction, including heart failure, remains a recognized safety concern. Biosimilar trastuzumab products have expanded treatment access and may reduce costs, although real-world data comparing their cardiac safety with the reference product remain limited. This study evaluated the uptake of biosimilar trastuzumab and compared heart failure risk between patients receiving biosimilar and reference trastuzumab in routine clinical practice.

DETAILS: The investigators analyzed patients aged ≥18 years with breast cancer who received trastuzumab between 2018 and 2024 using the IQVIA PharMetrics Plus Closed Health Plan Claims database. Patients who underwent breast cancer surgery within the first year after diagnosis were considered to have early-stage disease. Individuals with a heart failure diagnosis before breast cancer surgery were excluded. Trastuzumab products were identified using Healthcare Common Procedure Coding System Level II codes, while heart failure was identified using International Classification of Diseases codes. The analysis used multivariable cause-specific Cox proportional hazards regression to evaluate the association between trastuzumab type and subsequent heart failure risk. The study included 5,135 patients, of whom 43.9% received reference trastuzumab.

Use of biosimilar trastuzumab increased substantially during the study period, from 0% in 2018 to 71.3% in 2024 (P<0.001). Overall, heart failure occurred in 5.9% of patients, including 5.5% of those receiving reference trastuzumab and 6.3% of those receiving biosimilar trastuzumab (P=0.26). After adjustment for relevant factors, there was no statistically significant difference in heart failure risk between biosimilar and reference trastuzumab (adjusted HR, 1.16; 95% CI, 0.92-1.46). In contrast, patients with a Charlson Comorbidity Index score ≥2 had a higher heart failure risk than those with a score of 0 (adjusted HR, 1.52; 95% CI, 1.11-2.08). Older age was also associated with greater risk: compared with patients aged 18-54 years, the adjusted HR was 1.61 (95% CI, 1.19-2.19) for those aged 65-74 years and 1.95 (95% CI, 1.29-2.96) for those aged ≥75 years.

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Source: Jackson, I., Zhang, N., Sullivan, M., et al. Real-World Cardiotoxicity of Biosimilar versus Reference Trastuzumab in Early HER2-Positive Breast Cancer. JACC: CardioOncology. Published: September 10, 2026. DOI: 10.1016/j.jaccao.2026.07.009.

[Posted 22/Sep/2026]

AUDIENCE: Ophthalmology, Endocrinology, Internal Medicine

KEY FINDINGS: The development of NVG was associated with additional long-term systemic morbidity and mortality beyond the underlying PDR or CRVO in this large retrospective cohort. The strongest associations included mortality and ESRD among patients with PDR and mortality and stroke among those with CRVO. The findings suggest that development of NVG may identify patients with substantial systemic vascular risk and support closer coordination between ophthalmic and other medical specialties. Because the study was retrospective and based on electronic health records, the observed associations should not be interpreted as evidence that NVG itself directly causes these systemic outcomes.

BACKGROUND: Neovascular glaucoma (NVG) is a serious ocular complication of retinal vascular disease, including proliferative diabetic retinopathy (PDR) and central retinal vein occlusion (CRVO). Although NVG is primarily recognized for its effects on vision and intraocular pressure, less is known about whether its development is associated with additional long-term systemic health risks. This multicenter retrospective cohort study evaluated mortality and major systemic outcomes among adults with PDR or CRVO who did or did not subsequently develop NVG.

DETAILS: The investigators used the TriNetX Research Network, a deidentified electronic health record database containing information from more than 177 million patients across more than 150 healthcare organizations worldwide. Adults older than 40 years with PDR or CRVO were identified and compared according to whether NVG subsequently developed. Patients were propensity-score matched 1:1 based on demographic characteristics and comorbidities. Outcomes were assessed at 1, 5, and 10 years and included all-cause mortality, stroke, myocardial infarction (MI), end-stage renal disease (ESRD), and deep-vein thrombosis (DVT). A total of 1,278 patients with PDR and NVG were matched with 1,278 patients with PDR without NVG. The study also evaluated patients with CRVO and NVG compared with matched CRVO patients without NVG, as well as an NVG cohort compared with a cataract control cohort.

Among patients with PDR, development of NVG was associated with higher 10-year mortality (HR, 1.34; 95% CI, 1.14-1.57) and ESRD (HR, 1.43; 95% CI, 1.23-1.67) compared with PDR without NVG. Ten-year survival was 60.4% in the PDR + NVG group compared with 68.4% in the PDR without NVG group. Among patients with CRVO, those who developed NVG had higher 10-year mortality (HR, 1.61; 95% CI, 1.17-2.20) and stroke risk (HR, 1.86; 95% CI, 1.19-2.90). Differences in MI and ESRD were not statistically significant in this comparison, and DVT risk was also not significantly different. When PDR + NVG was compared directly with CRVO + NVG, the PDR + NVG group had higher 10-year risks of mortality (HR, 1.56; 95% CI, 1.17-2.07), MI (HR, 1.94; 95% CI, 1.13-3.32), and ESRD (HR, 4.04; 95% CI, 2.43-6.73). Compared with the cataract control cohort, NVG was associated at 10 years with higher risks of mortality (HR, 2.66; 95% CI, 2.40-2.94), stroke (HR, 2.17; 95% CI, 1.85-2.54), MI (HR, 1.89; 95% CI, 1.60-2.23), and ESRD (HR, 3.34; 95% CI, 2.89-3.88).

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Source: Margolis, R., Vasu, P., and Dorairaj, S. K. Long-Term Risk of Mortality and Systemic Morbidity in Neovascular Glaucoma: A Multicenter Retrospective Cohort Study. Ophthalmology Glaucoma. 2026; 9(5): 517-526. Published: September-October, 2026. DOI: 10.1016/j.ogla.2026.01.017.