Daily Cardiology Research Analysis
A pooled randomized analysis in Lancet shows that high-dose influenza vaccine reduces influenza/pneumonia and cardiorespiratory hospitalizations in older adults. A large echocardiography cohort identifies a U-shaped link between left ventricular ejection fraction and worsening heart failure, highlighting risk at supranormal EF. An individual patient-level meta-analysis finds suture-based ProGlide superior to plug-based MANTA for large-bore vascular closure after TAVI, lowering vascular and bleed
Summary
A pooled randomized analysis in Lancet shows that high-dose influenza vaccine reduces influenza/pneumonia and cardiorespiratory hospitalizations in older adults. A large echocardiography cohort identifies a U-shaped link between left ventricular ejection fraction and worsening heart failure, highlighting risk at supranormal EF. An individual patient-level meta-analysis finds suture-based ProGlide superior to plug-based MANTA for large-bore vascular closure after TAVI, lowering vascular and bleeding complications.
Research Themes
- Vaccination strategies to reduce cardiopulmonary hospitalizations in older adults
- Risk stratification across the full spectrum of left ventricular ejection fraction
- Optimization of large-bore vascular closure in transcatheter interventions
Selected Articles
1. Effectiveness of high-dose influenza vaccine against hospitalisations in older adults (FLUNITY-HD): an individual-level pooled analysis.
Across 466,320 randomized participants, high-dose influenza vaccine reduced hospitalisation for influenza or pneumonia versus standard dose (relative vaccine effectiveness 8.8%). It also reduced cardiorespiratory, laboratory-confirmed influenza, and all-cause hospitalisations, with similar all-cause mortality and serious adverse events.
Impact: This prespecified pooled analysis of two harmonized randomized trials provides robust evidence that high-dose influenza vaccination confers superior protection against severe clinical outcomes in older adults, informing vaccine policy.
Clinical Implications: Preferential use of high-dose inactivated influenza vaccine in older adults may reduce influenza/pneumonia and cardiorespiratory hospitalizations without increasing serious adverse events, and should be considered in immunization programs.
Key Findings
- Primary endpoint: hospitalisation for influenza or pneumonia was lower with HD-IIV vs SD-IIV (rVE 8.8%, 95% CI 1.7–15.5; one-sided p=0.0082).
- Secondary endpoints: reductions with HD-IIV in cardiorespiratory hospitalisation (rVE 6.3%), laboratory-confirmed influenza hospitalisation (rVE 31.9%), and all-cause hospitalisation (rVE 2.2%).
- All-cause mortality and serious adverse events were similar between groups.
Methodological Strengths
- Prespecified individual-level pooled analysis of two harmonized randomized trials with >460,000 participants.
- Registry-linked outcomes and hierarchical testing of clinically relevant endpoints.
Limitations
- Geographic scope limited to Denmark and Galicia (Spain), potentially affecting generalizability.
- No mortality benefit demonstrated; potential confounding by circulating strains across seasons.
Future Directions: Head-to-head cost-effectiveness analyses and implementation studies across diverse health systems; evaluation in very old, frail, or multimorbid populations and in coadministration settings.
BACKGROUND: Two large-scale trials comparing high-dose inactivated influenza vaccine (HD-IIV) versus standard-dose inactivated influenza vaccine (SD-IIV) against hospitalisation outcomes have been conducted in Denmark and Spain. We aimed to analyse the pooled data from these trials to enhance generalisability and assess the relative vaccine effectiveness (rVE) of HD-IIV versus SD-IIV against severe clinical outcomes in older adults. METHODS: FLUNITY-HD was a prespecified, individual-level pooled analysis of two methodologically harmonised pragmatic, individually randomised trials comparing HD-IIV with SD-IIV in older adults. DANFLU-2 included adults aged 65 years or older and GALFLU included community-dwelling adults aged 65-79 years. DANFLU-2 was conducted during the 2022-23, 2023-24, and 2024-25 influenza seasons in Denmark, whereas GALFLU was conducted during the 2023-24 and 2024-25 seasons in Galicia, Spain. In both trials, participants were randomly assigned (1:1) to receive either HD-IIV (60 µg of haemagglutinin [HA] antigen per strain) or SD-IIV (15 µg of HA antigen per strain) and followed up for the occurrence of endpoints from 14 days after vaccination to May 31 the following year in each season. Routine health-care databases were used as primary data source. The primary endpoint of both the pooled analysis and the individual trials was hospitalisation for influenza or pneumonia. Secondary endpoints were tested hierarchically, and consisted of hospitalisation for any cardiorespiratory disease, laboratory-confirmed influenza hospitalisation, all-cause hospitalisation, all-cause mortality, hospitalisation for influenza (ICD-10), and hospitalisation for pneumonia.
2. A U-shaped relationship between left ventricular ejection fraction and risk of worsening heart failure.
In 93,694 adults, LVEF showed a U-shaped association with the composite of all-cause death or worsening heart failure, with lowest risk at 60–70% and increased risk when LVEF was ≥70%. The pattern held across age, sex, and comorbid subgroups and for both incident and recurrent HF events.
Impact: This large cohort extends the U-shaped paradigm of LVEF from mortality to worsening HF, identifying supranormal EF (≥70%) as a high-risk phenotype that may warrant tailored monitoring and management.
Clinical Implications: Patients with supranormal LVEF may merit closer surveillance and targeted evaluation for diastolic dysfunction, hypertrophy, or infiltrative disease despite preserved or high EF.
Key Findings
- U-shaped association between LVEF and composite of all-cause mortality or worsening HF, with nadir at 60–70%.
- Supranormal LVEF (≥70%) associated with higher risk for the composite (aHR 1.12) and for worsening HF (aHR 1.13).
- Findings consistent across age, sex, hypertension, diabetes subgroups, and for incident and recurrent HF events.
Methodological Strengths
- Very large single-center cohort with granular 5% LVEF categories.
- Long median follow-up (8.3 years) with multiple clinically relevant outcomes.
Limitations
- Observational design from a tertiary center; residual confounding and referral bias are possible.
- Lack of detailed phenotyping (e.g., strain, biomarkers) to elucidate mechanisms at high EF.
Future Directions: Prospective, multiethnic validation with mechanistic profiling (imaging, biomarkers) to define drivers of risk at supranormal EF and to test tailored management strategies.
AIMS: Left ventricular ejection fraction (LVEF) is a key measure of cardiac function. While prior studies showed a U-shaped relationship between LVEF and mortality, its association with worsening heart failure (HF) remains unclear. We aimed to evaluate the association between the full spectrum of LVEF and the risk of worsening HF. METHODS AND RESULTS: We analysed data from 93 694 consecutive participants (median age 62 years [interquartile range: 50-76 years], 51.4% men) undergoing echocardiography at a tertiary medical centre. LVEF, measured by biplane Simpson's method, was categorized into 5% intervals from <20% to ≥70%. The primary outcome was a composite of all-cause mortality or worsening HF, while the secondary outcomes included all-cause mortality, cardiovascular death, and worsening HF. The primary outcome occurred in 32 398 (34.6%) participants over a median follow-up of 8.3 years. A U-shaped relationship between LVEF and the primary outcome was observed, with a nadir at 60-70% and an increased risk when LVEF was ≥70% [adjusted hazard ratio (aHR) 1.12; 95% confidence interval (CI) 1.06-1.18]. Similar patterns were observed for the secondary outcomes. Participants with LVEF ≥70% also had a higher risk of worsening HF (aHR 1.13, 95% CI 1.03-1.23). This U-shaped association was consistent across subgroups stratified by age, sex, hypertension, and diabetes, and was observed for both incident and recurrent HF events.
3. Suture-based versus plug-based closure for large-bore arterial access: an individual patient-level meta-analysis of randomised trials.
Pooling individual data from two randomized TAVI trials (n=722), suture-based ProGlide reduced VARC-3 access-site vascular complications versus plug-based MANTA (OR 0.54) and lowered bleeding (OR 0.41). Need for endovascular stenting or vascular surgery was also lower with ProGlide (OR 0.22).
Impact: Access-site complications are a major driver of morbidity in large-bore interventions. This IPD meta-analysis provides comparative randomized evidence to guide device selection.
Clinical Implications: For transfemoral TAVI requiring large-bore access, suture-based closure with ProGlide should be favored to minimize vascular and bleeding complications and reinterventions.
Key Findings
- ProGlide reduced access site-related vascular complications vs MANTA (OR 0.54, 95% CI 0.35–0.82).
- Access site-related bleeding events were lower with ProGlide (OR 0.41, 95% CI 0.18–0.94).
- ProGlide reduced need for endovascular stenting or vascular surgery (OR 0.22, 95% CI 0.06–0.79); no subgroup favored MANTA.
Methodological Strengths
- Individual patient-level meta-analysis of randomized trials with standardized VARC-3 outcomes.
- Prespecified subgroup analyses to explore effect modifiers.
Limitations
- Only two randomized trials and 722 patients; external validity beyond TAVI populations may be limited.
- Operator experience and device learning curves could influence outcomes but are difficult to fully standardize.
Future Directions: Head-to-head randomized trials across broader anatomies and access sizes; cost-effectiveness analyses; training and standardization strategies to optimize closure outcomes.
BACKGROUND: Percutaneous large-bore arteriotomy closure devices are either suture- or plug-based. The comparative efficacy and safety of both techniques and optimal patient selection remain controversial. AIMS: We aimed to conduct a patient-level meta-analysis of randomised trials comparing suture-based ProGlide versus plug-based MANTA large-bore vascular closure devices (VCDs). METHODS: We searched PubMed, the Cochrane Central Register of Controlled Trials, and Google Scholar for randomised controlled trials comparing vascular closure with the ProGlide-based and the MANTA-based technique. The primary endpoint of this analysis was access site-related vascular complications defined according to the Valve Academic Research Consortium-3 criteria. RESULTS: We identified 2 trials that enrolled a total of 722 patients undergoing transcatheter aortic valve implantation. The primary endpoint was significantly less common after vascular closure with the ProGlide-based technique (odds ratio [OR] 0.54, 95% confidence interval [CI]: 0.35-0.82). Access site-related bleeding events were also less common with the ProGlide-based technique (OR 0.41, 95% CI: 0.18-0.94). Prespecified subgroup analyses did not reveal any subgroup favouring the plug-based technique. Clinical outcomes with the MANTA-based technique were better in larger-sized vessels. Patients who received the ProGlide-based technique were less likely to undergo endovascular stenting or vascular surgery (OR 0.22, 95% CI: 0.06-0.79). CONCLUSIONS: In this patient-level meta-analysis of randomised trials, the ProGlide-based technique for large-bore arterial access was superior to the MANTA-based technique in terms of vascular and bleeding complications.