BACKGROUND:Sex differences in chronic heart failure are well established, but corresponding differences in acute heart failure (AHF), particularly in multimodal imaging findings and short-term recovery, remain incompletely characterized. METHODS:In this prospective observational study, 567 adults hospitalized with AHF underwent clinical assessment, laboratory testing, transthoracic echocardiography, and lung ultrasound during the early in-hospital phase (median 2 days after admission) and 1-3 months after discharge. The primary endpoint was the composite of all-cause mortality or heart failure readmission within 180 days. RESULTS:Among 567 patients (mean age 78.2±11.6 years), 248 (43.7%) were female. Females were older and more frequently had atrial fibrillation and hypertension, whereas males more frequently had dyslipidemia and ischemic heart disease. Females more frequently presented with palpitations and peripheral edema, whereas males more frequently reported chest pain. During the early in-hospital assessment, females had higher left ventricular ejection fraction (38% vs. 35%, p<0.001), higher absolute global longitudinal strain (10.5±4.7% vs. 9.7±4.4%, p=0.04), lower left ventricular mass index (113 vs. 136 g/m2, p<0.001), and higher relative wall thickness (0.51 vs. 0.47, p=0.002). Males had a higher lung ultrasound B-line count (5 [1-12] vs. 2 [0-9], p=0.003). Among patients completing follow-up, improvements in cardiac function, congestion, and NT-proBNP were similar between sexes. No statistically significant sex differences were observed in the 180-day composite outcome. CONCLUSIONS:Females and males hospitalized with AHF exhibited distinct clinical presentation and imaging profiles during the early in-hospital assessment. Among patients completing follow-up, short-term recovery was similar between sexes, with no statistically significant sex differences in 180-day clinical outcomes.

Trial registration NCT06684743, registered 9 November 2024 (https://clinicaltrials.gov/study/NCT06684743).

In this prespecified analysis of DANFLU-2, including the largest CKD population ever in an individually randomized vaccine trial, we observed a benefit of HD-IIV vs SD-IIV against hospitalization for influenza or pneumonia, as well as hospitalization for influenza, with suggestion of a greater relative benefit among those with CKD. Furthermore, the beneficial effect of HD-IIV vs SD-IIV on multiple cardiorespiratory outcomes was consistent across participants irrespective of CKD status.

Importance:The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against laboratory-confirmed influenza infection vs standard-dose IIV (SD-IIV); however, data regarding its effectiveness against cardiovascular (CV) outcomes are mainly from observational studies or specific high-risk groups. Objective:To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against CV outcomes in the general older adult population in Denmark. Design, Setting, and Participants:This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial (RCT) using nationwide administrative health registries in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Older adults (age ≥65 years) were eligible for inclusion regardless of comorbidity. The trial design specified that if the primary end point was neutral, no hypothesis testing would be performed for secondary or exploratory end points. Data were analyzed from June 29 to August 12, 2025. Interventions:Individual-level 1:1 randomization to HD-IIV or SD-IIV. Participants re-enrolling in additional seasons were rerandomized. Main Outcomes and Measures:Severe CV outcomes were prespecified secondary and exploratory end points in the trial, occurring from 14 days after vaccination through May 31 the following year. Results:A total of 332 438 participants (170 900 [51.4%] male; mean [SD] age, 73.7 [5.8] years) were randomized (166 218 to HD-IIV and 166 220 to SD-IIV), of whom 91 026 (27.4%) had a history of CV disease. HD-IIV did not significantly reduce the trial's primary end point of hospitalization for influenza or pneumonia. The incidence of hospitalization for any cardiorespiratory disease was lower in the HD-IIV group than the SD-IIV group (rVE, 5.7% [95% CI, 1.4% to 9.9%]; absolute difference, -0.13 [95% CI, -0.24 to -0.03] percentage points), and rVE did not differ by history of CV disease compared with no CV disease at baseline. Hospitalization for any CV disease occurred in fewer participants in the HD-IIV group than the SD-IIV group (rVE, 7.5% [95% CI, 1.5% to 12.5%]; absolute difference, -0.10 [95% CI, -0.18 to -0.02] percentage points) as did hospitalization for heart failure (rVE, 19.5% [95% CI, 3.3% to 33.1%]; absolute difference, -0.03 [95% CI, -0.06 to -0.01] percentage points). Conclusions and Relevance:This study found reduced incidence of cardiorespiratory hospitalization among those who received HD-IIV vs SD-IIV, driven by a lower incidence of CV hospitalizations, and particularly heart failure hospitalizations. These differences should be interpreted as exploratory findings in the setting of a large RCT with a neutral primary outcome. Trial Registration:ClinicalTrials.gov Identifier: NCT05517174.

The high-dose inactivated influenza vaccine (HD-IIV) has demonstrated superior protection against laboratory-confirmed influenza infection vs standard-dose IIV (SD-IIV); however, data regarding its effectiveness against cardiovascular (CV) outcomes are mainly from observational studies or specific high-risk groups. To investigate the relative vaccine effectiveness (rVE) of HD-IIV vs SD-IIV against CV outcomes in the general older adult population in Denmark. This was a prespecified secondary analysis of DANFLU-2, a pragmatic, open-label, individually randomized clinical trial (RCT) using nationwide administrative health registries in Denmark during the 2022/2023 to 2024/2025 influenza seasons. Older adults (age ≥65 years) were eligible for inclusion regardless of comorbidity. The trial design specified that if the primary end point was neutral, no hypothesis testing would be performed for secondary or exploratory end points. Data were analyzed from June 29 to August 12, 2025. Individual-level 1:1 randomization to HD-IIV or SD-IIV. Participants re-enrolling in additional seasons were rerandomized. Severe CV outcomes were prespecified secondary and exploratory end points in the trial, occurring from 14 days after vaccination through May 31 the following year. A total of 332 438 participants (170 900 [51.4%] male; mean [SD] age, 73.7 [5.8] years) were randomized (166 218 to HD-IIV and 166 220 to SD-IIV), of whom 91 026 (27.4%) had a history of CV disease. HD-IIV did not significantly reduce the trial’s primary end point of hospitalization for influenza or pneumonia. The incidence of hospitalization for any cardiorespiratory disease was lower in the HD-IIV group than the SD-IIV group (rVE, 5.7% [95% CI, 1.4% to 9.9%]; absolute difference, −0.13 [95% CI, −0.24 to −0.03] percentage points), and rVE did not differ by history of CV disease compared with no CV disease at baseline. Hospitalization for any CV disease occurred in fewer participants in the HD-IIV group than the SD-IIV group (rVE, 7.5% [95% CI, 1.5% to 12.5%]; absolute difference, −0.10 [95% CI, −0.18 to −0.02] percentage points) as did hospitalization for heart failure (rVE, 19.5% [95% CI, 3.3% to 33.1%]; absolute difference, −0.03 [95% CI, −0.06 to −0.01] percentage points). This study found reduced incidence of cardiorespiratory hospitalization among those who received HD-IIV vs SD-IIV, driven by a lower incidence of CV hospitalizations, and particularly heart failure hospitalizations. These differences should be interpreted as exploratory findings in the setting of a large RCT with a neutral primary outcome. ClinicalTrials.gov Identifier: NCT05517174

BACKGROUND:Individuals with chronic lung disease (CLD) face an increased risk of influenza-related complications and mortality, and seasonal vaccination is recommended. Limited evidence exists on the effectiveness of high-dose (HD-IIV) vs. standard-dose (SD-IIV) inactivated influenza vaccines in this population. METHODS:DANFLU-1 trial was a pragmatic, open-label, randomized trial comparing HD-IIV vs. SD-IIV in adults aged 65-79 years during the 2021/2022 influenza season. Vaccines were allocated 1:1. CLD was identified using ICD-10 codes. The prespecified outcomes were hospitalizations due to pneumonia or influenza, respiratory, cardiovascular, cardiorespiratory, and all-cause hospitalizations, and mortality. RESULTS:The study population included 12,477 participants (mean age 71.7 ± 3.9 years, 47 % female), of whom 850 (6.8 %) had CLD. Hospitalization rates for all outcomes were significantly higher among participants with CLD. HD-IIV was associated with a lower risk of hospitalization for pneumonia or influenza (HR 0.36 (CI: 0.17-0.73); no CLD: HR 0.22 (CI: 0.08-0.57); CLD: HR 0.95 (CI: 0.28-3.30); p for interaction = 0.064), respiratory hospitalization, and all-cause mortality, and a lower incidence rate of all-cause hospitalization. Effect estimates were less favorable for HD-IIV compared to SD-IIV among CLD patients in preventing respiratory disease hospitalization and all-cause mortality. CONCLUSION:In this prespecified analysis of the DANFLU-1 randomized trial of HD-IIV vs. SD-IIV, trends suggested that among participants with CLD, the benefit of HD-IIV may be attenuated compared with those without CLD, particularly in relation to respiratory disease hospitalization and all-cause mortality. Given the small sample size, these results should be considered hypothesis-generating and require further investigation. TRIAL REGISTRATION:ClinicalTrials.gov: NCT05048589.

BACKGROUND:Radiofrequency catheter ablation (RFA) plays an increasing role in the treatment of ventricular arrhythmias (VAs). This study aimed to evaluate the echocardiographic and clinical characteristics of patients undergoing first-time RFA for VAs and to identify risk factors associated with VA recurrence, implantable cardioverter-defibrillator (ICD) therapy, and mortality. METHODS:We studied patients scheduled for first-time RFA for VAs from 2011 to 2022 with available transthoracic echocardiography before the procedure. The primary outcome was defined as VA recurrence, and the secondary outcome was defined as appropriate ICD therapy and mortality. Uni- and multivariable Cox hazards regression models were used to assess the prognostic value of cardiac structure and function by echocardiography. RESULTS:A total of 218 patients (mean age 61 years [±15], 62% men, mean LVEF 51% [IQR: 44; 57]) underwent RFA during the study period. Of these, 90 patients (41%) had VA recurrence while 52 patients (24%) developed the secondary outcome during a median follow-up time of 3.1 years (IQR: 1.1; 6.7 years). Patients with ventricular tachycardia had significantly more right-and left ventricular (LV) dysfunction, compared to patients with premature ventricular contractions. No echocardiographic measures were associated with VA recurrence, while several echocardiographic measures were associated with the secondary outcome. LV mass index, LV ejection fraction, global longitudinal strain, and VA recurrence showed the highest predictive values of the secondary outcome. CONCLUSION:In patients undergoing RFA for VAs, several echocardiographic measures may identify patients at risk of an adverse outcome.

This prespecified secondary analysis of a randomized clinical trial investigates the risk of myocarditis or pericarditis with high-dose vs standard-dose inactivated influenza vaccine among older adults.

BACKGROUND AND AIMS:The aim was to evaluate and compare the relative vaccine effectiveness (rVE) of high-dose (HD-IIV) vs. standard-dose inactivated influenza vaccination (SD-IIV) on respiratory and cardiovascular outcomes in persons with or without pre-existing atherosclerotic cardiovascular disease (ASCVD). METHODS:A prespecified exploratory analysis of a pragmatic, open-label, individually randomized trial conducted in Denmark during three influenza seasons. Adults ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Baseline and outcome data were collected through nationwide registries. The primary outcome was hospitalization for influenza or pneumonia. Major adverse cardiovascular events (MACE) was defined as a composite of cardiovascular death, hospitalization for myocardial infarction, or hospitalization for stroke. Heterogeneity in rVE among participants with vs. without ASCVD was assessed. RESULTS:The incidence of all outcomes was higher in participants with pre-existing ASCVD (n = 46 825) vs. those without (n = 285 613). rVE was consistent among participants with and without ASCVD (all Pinteraction ≥ .05). The rVE for the primary outcome was 6.87% [95% confidence interval (CI), -2.52 to 15.42] among individuals without ASCVD and 4.71% (95% CI, -11.58 to 18.63) in those with (Pinteraction = .80). For influenza hospitalizations, the rVE was 42.88% (95% CI, 22.07-58.44) vs. 45.73% (95% CI, 16.68-65.16) in those without vs. with ASCVD (Pinteraction = .84). For MACE, the rVE was 4.29% (95% CI, -6.50 to 14.00) in participants without, and 0.30% (95% CI, -17.56 to 15.44) in participants with, pre-existing ASCVD (Pinteraction = .68). CONCLUSIONS:Among individuals ≥65 years, the rVE of HD-IIV vs. SD-IIV against respiratory and cardiovascular outcomes was similar among those with vs. without pre-existing ASCVD.

BACKGROUND:Influenza contributes substantially to disease burden in individuals with heart failure (HF) and is an established trigger of cardiovascular and HF events. Standard-dose inactivated influenza vaccine (SD-IIV) is recommended for HF, though immune responses may be attenuated. High-dose inactivated influenza vaccine (HD-IIV) was developed to enhance immunogenicity, but its effectiveness compared with SD-IIV against hospitalization for influenza and cardiovascular disease by HF status remains uncertain. METHODS:This was a prespecified analysis of a pragmatic, prospective, individually randomized, open-label trial with registry-based end point-evaluation conducted in Denmark across the 2022/2023 to 2024/2025 influenza seasons. Citizens ≥65 years were randomized 1:1 to HD-IIV or SD-IIV. Outcomes included hospitalization for influenza-related illness, laboratory-confirmed influenza, any cardiovascular disease, cardio-respiratory disease, and HF, assessed by HF status. Effect of HD-IIV versus SD-IIV in reducing risk of outcomes assessed was expressed as risk ratios. RESULTS:The trial randomized 332 438 participants (48.6% female; mean age, 73.7±5.8 years), including 10 410 with HF at baseline (27.4% female; mean age, 76.0±6.3 years). Overall, HD-IIV was associated with a statistically significant lower incidence of hospitalization for influenza-related illness, laboratory-confirmed influenza, cardio-respiratory disease, cardiovascular disease, and HF compared with SD-IIV. In participants with HF, effect estimates were similar: risk ratio for influenza-related hospitalization was 0.48 (95% CI, 0.20-1.06; Pinteraction=0.64), for laboratory-confirmed influenza hospitalization 0.55 (95% CI, 0.29-1.02; Pinteraction=0.59), for cardio-respiratory hospitalization 0.89 (95% CI, 0.77-1.02; Pinteraction=0.34), for cardiovascular hospitalization 0.86 (95% CI, 0.72-1.02; Pinteraction=0.34), and for HF hospitalization 0.82 (95% CI, 0.61-1.11; Pinteraction=0.83). Findings were consistent across HF subgroups by disease duration, recency of hospitalization, most recent NT-proBNP (N-terminal pro-B-type natriuretic peptide), and presence of device therapy. CONCLUSIONS:In this prespecified exploratory analysis of the largest individually randomized influenza vaccine trial ever conducted, HD-IIV was associated with lower rates of influenza and cardiovascular hospitalizations compared with SD-IIV, with effect estimates similar across HF status at baseline and HF subgroups. REGISTRATION:URL: https://www.clinicaltrials.gov; Unique identifier: https://clinicaltrials.gov/study/NCT05517174.

Abstract Background Human Immunodeficiency Virus (HIV) has become a treatable, chronic condition, but people with HIV still face an elevated risk of cardiovascular disease, including heart failure. Purpose To assess echocardiographic alterations in left ventricular (LV) function in a contemporary cohort of well-treated people with HIV compared to the general population. Methods We included 744 people with HIV frequency matched 1:1 on age and sex with controls from the general population. Both people with HIV and controls underwent echocardiography, physical examination, questionnaires and blood sampling according to similar study protocols. LV systolic dysfunction was defined as LV ejection fraction (LVEF) <50% or absolute global longitudinal strain (GLS) <16%. LV diastolic function was defined as abnormal if the following was true for half or more available parameters: (1) average E/e’>14, (2) septal e’ velocity < 7 cm/s or lateral e’ velocity <10cm/s, (3) tricuspid regurgitation velocity >2.8 m/s, (4) left atrial volume index >34ml/m2. Associations between HIV status and LV function were assessed using linear and logistic regression models adjusted for age, sex, smoking, hypertension, diabetes mellitus, total cholesterol and high-sensitivity C-reactive protein. Among people with HIV, the association between HIV-specific characteristics and LV function were assessed using logistic regression models with adjustment for the same potential confounders. Results Mean age was 53.4 years and 88% were male. For people with HIV, median time since HIV diagnosis was 18 years and 99% received antiretroviral therapy. People with HIV had lower adjusted mean absolute GLS [17.6 vs. 18.5%, p<0.001], E/A ratio [1.0 vs. 1.2, p<0.001] and average e’ [9.5 vs. 10.5 cm/s, p<0.001] than controls, while LVEF and E/e’ were not significantly different between people with HIV and controls (Figure 1). HIV was associated with impaired systolic function as assessed by GLS [odds ratio 1.70, 95% CI: 1.17-2.46, p=0.005], but not when assessed by LVEF [odds ratio 1.06, 95% CI: 0.78-1.45, p=0.69](Figure 2). Living with HIV was not associated with diastolic dysfunction compared to controls [odds ratio 0.97, 95% CI: 0.61-1.52, p=0.88], but longer HIV-duration was associated with higher odds of diastolic dysfunction among people with HIV (odds ratio 1.06, 95% CI: 1.02-1.10 per year, p=0.004). Current antiretroviral medication type, previous AIDS defining conditions, current CD4+ count and detectable viral load were not associated with LV dysfunction. Conclusion People with HIV show signs of early impairments in longitudinal LV systolic function compared to the general population. These subclinical changes may underlie the increased risk of heart failure observed in PWH.

Background The extent of cardiac involvement in cystic fibrosis (CF) remains to be determined. The remarkable therapeutic advancements with new highly effective cystic fibrosis transmembrane conductance regulator (CFTR) modulator treatment and subsequent increase in life expectancy substantiates further research. We aimed to explore the prevalence of cardiac alterations in people with CF (pwCF) compared to matched controls and investigate potential cardiovascular risk factors. Methods In this cross-sectional study, 104 pwCF underwent clinical and echocardiographic assessment. All participants were matched 1:1 with controls from the general population. Results Of 104 pwCF, 44 % were female, mean age was 34 years, and 93 % received CFTR modulator treatment. The prevalence of abnormal cardiac function in pwCF was 44 %, more than double the prevalence in controls. PwCF were found to have smaller left ventricular (LV) dimensions, worse LV diastolic function, and reduced right ventricle (RV) as well as LV systolic function. After multivariable adjustment, LV diastolic function as well as LV and RV systolic function remained poorer in pwCF as compared to controls. Male sex and decreasing FEV1/FVC ratio remained independently associated with abnormal cardiac function in pwCF (male sex: OR 3.94 (1.56; 9.95), p = 0.004 and FEV1/FVC ratio: OR 2.05 per 0.1 unit decrease (1.21; 3.52), p = 0.008, respectively). Conclusions Both left- and right-sided cardiac alterations were found in pwCF. After adjustments for risk factors, both RV and LV systolic measures remained altered in pwCF, compared to controls. Male sex and decreasing pulmonary function evaluated by FEV1/FVC-ratio were associated with abnormal cardiac function in pwCF.