Daily Cardiology Research Analysis
A randomized trial in acute stroke (DAYLIGHT) shows that extending CT angiography below the carina quintupled detection of cardioaortic thrombi without delaying imaging. The first multicenter, blinded RCT of fecal microbiota transplantation for hypertension demonstrated safety but an unsustained blood pressure effect alongside microbiome–metabolome shifts. A systematic review/meta-analysis suggests managing systolic blood pressure to <130 mmHg in HFpEF lowers heart failure hospitalizations, with
Summary
A randomized trial in acute stroke (DAYLIGHT) shows that extending CT angiography below the carina quintupled detection of cardioaortic thrombi without delaying imaging. The first multicenter, blinded RCT of fecal microbiota transplantation for hypertension demonstrated safety but an unsustained blood pressure effect alongside microbiome–metabolome shifts. A systematic review/meta-analysis suggests managing systolic blood pressure to <130 mmHg in HFpEF lowers heart failure hospitalizations, with increased hypotension risk but no signal for renal harm.
Research Themes
- Imaging optimization to uncover cardioembolic sources in acute stroke
- Microbiome-based interventions and cardiometabolic regulation
- Blood pressure targets in HFpEF and clinical outcomes
Selected Articles
1. Extended CT angiography versus standard CT angiography for the detection of cardioaortic thrombus in patients with ischaemic stroke and transient ischaemic attack (DAYLIGHT): a prospective, randomised, open-label, blinded end-point trial.
In the DAYLIGHT randomized trial, extending CTA at least 6 cm below the carina increased detection of cardioaortic thrombi from 1.7% to 8.8% without prolonging imaging time. The design was single-centre, open-label with blinded endpoint adjudication and included 465 patients with ischaemic stroke/TIA.
Impact: This RCT demonstrates a practical imaging change that substantially increases detection of actionable thrombi without workflow penalty, potentially enabling earlier anticoagulation and secondary prevention.
Clinical Implications: Acute stroke protocols could consider extended CTA to improve detection of cardioaortic thrombi and inform early anticoagulation decisions; outcome and cost-effectiveness studies are warranted.
Key Findings
- Extended CTA detected cardioaortic thrombi in 8.8% vs 1.7% with standard CTA (OR 5.70, 95% CI 1.92–16.96; p=0.002).
- No significant delay in imaging: median time to CTA completion 21.0 vs 20.0 minutes (p=0.67).
- Randomized 830 patients; modified ITT analysis included 465 with ischaemic stroke/TIA after excluding stroke mimics.
Methodological Strengths
- Prospective randomized design with blinded endpoint adjudication and trial registration.
- Direct workflow metric assessment showing non-inferiority in imaging time.
Limitations
- Single-centre study; generalizability needs multicentre validation.
- Primary outcome was diagnostic yield; impact on recurrent stroke and clinical outcomes remains untested.
Future Directions: Multicentre pragmatic trials assessing whether extended CTA-guided management reduces recurrent stroke; radiation/contrast risk–benefit analyses and cost-effectiveness; subgroup analyses (e.g., renal dysfunction).
BACKGROUND: Cardioembolic sources often remain undetected after standard diagnostic stroke workup, contributing to high rates of recurrence. We aimed to assess whether a head-to-neck CT angiography extended at least 6 cm below the carina (extended CT angiography) can increase the detection of cardioaortic thrombi compared with standard-of-care CT angiography (standard CT angiography) in patients with ischaemic stroke or transient ischaemic attack. METHODS: This single-centre, prospective, randomised, open-label, blinded end-point trial was done at London Health Sciences Centre, Western University, Canada. Eligible patients were adults aged 18 years or older with ischaemic stroke or transient ischaemic attack assessed during acute code strokes. Exclusion criteria were known allergy or concerns about the safety of iodinated contrast agents (eg, severe renal failure) and no intravenous access. Participants were randomly assigned in a 1:1 ratio to receive standard CT angiography or extended CT angiography. Patients, neurologists adjudicating qualifying events, cardiothoracic radiologists, and cardiologists adjudicating study outcomes were masked to randomisation. Adjudicators were considered masked to randomisation as they did not know which patients were crossovers, which patients in the standard of care arm had partial imaging of the left atrial appendage due to normal variations in size and shape, and which patients in the extended CT angiography group also had partial imaging of the left atrial appendage instead of full imaging. The primary efficacy outcome was the detection of a cardioaortic thrombus (modified intention-to-treat population). The primary safety outcome was time to CT angiography completion (as-treated population). The trial was registered at ClinicalTrials.gov, NCT05522244, and is closed. FINDINGS: Between July 17, 2023, and May 6, 2024, 963 patients were assessed for inclusion. 133 were excluded because they already had a CT angiography at their local hospital, intracranial haemorrhage was identified on the initial non-contrast CT, a diagnosis of stroke was considered highly unlikely by the treating stroke neurologist, or randomisation was not possible. 830 patients were enrolled and randomly assigned to extended CT angiography (n=415) or standard CT angiography (n=415). One patient withdrew consent and was excluded from the analyses. 364 participants who were later adjudicated as having experienced stroke mimics were excluded. 465 patients with ischaemic stroke or transient ischaemic attack were included in the modified intention-to-treat population (226 in the extended CT angiography group and 239 in the standard CT angiography group). 239 (51%) of 465 patients were female and 226 (49%) were male. Median age of the analysis group at enrolment was 78·0 years (IQR 69·0-84·0). The primary outcome (cardioaortic thrombus) was detected in 20 (8·8%) of 226 patients in the extended CT angiography group and four (1·7%) of 239 in the standard CT angiography group (odds ratio 5·70, 95% CI 1·92-16·96; p=0·002). There were no statistically significant differences in the median time from code stroke activation to CT angiography completion between the extended CT angiography group (21·0 min; IQR 15·8-27·0 min) and the standard CT angiography group (20·0 min, 17·0-26·0 min). The median difference between extended CT angiography and standard CT angiography groups was 1·0 min (-1·0 to 2·5), p=0·67). INTERPRETATION: Performing extended CT angiography during acute code strokes is feasible and results in increased cardioaortic thrombi detection without causing delays in CT angiography completion. Future studies should assess whether extended CT angiography can reduce recurrent stroke risk by prompting early anticoagulation after thrombus detection. FUNDING: Western University, and the Kathleen and Dr Henry Barnett Chair in Stroke Research.
2. Fecal microbiota transplantation for hypertension: an exploratory, multicenter, randomized, blinded, placebo-controlled trial.
In this multicenter, randomized, blinded, placebo-controlled trial (n=124), FMT was safe but did not significantly reduce office SBP at 30 days versus placebo, despite an early 1-week between-arm reduction of −4.34 mmHg that was not sustained. FMT induced reproducible shifts in specific microbial taxa and plasma metabolites that correlated with SBP.
Impact: This is the first blinded RCT testing FMT for hypertension, establishing safety and delineating microbiome–metabolome correlates, which reframes future microbial therapeutics toward targeted consortia rather than whole-FMT.
Clinical Implications: FMT capsules should not be used for routine hypertension control; future clinical studies should focus on defined microbial consortia with metabolite-targeted, BP-modulating properties and biomarker-guided engraftment.
Key Findings
- Primary endpoint was neutral: mean SBP change at day 30 was similar (6.28 vs 5.77 mmHg; p=0.62).
- Early effect: week-1 SBP reduction favored FMT by −4.34 mmHg (95% CI −8.1 to −0.58; p=0.024) but waned despite repeat dosing.
- Safety comparable to placebo (AEs 20.6% vs 14.8%; p=0.39) with significant shifts in taxa (e.g., Parabacteroides merdae↑, Eggerthella lenta↓) and metabolites correlating with SBP.
Methodological Strengths
- Multicentre, randomized, double-blind, placebo-controlled design with ITT analysis.
- Integrated multi-omics (microbiome and metabolome) linking taxa and metabolites to BP.
Limitations
- Short follow-up (primary at 30 days; safety to 3 months) and relatively young cohort (mean age 43).
- Whole-FMT approach may dilute specific BP-modulating effects; engraftment not ensured.
Future Directions: Test defined microbial consortia with mechanistic metabolites (e.g., amino acid pathways), optimize dosing/engraftment, and enrich responders via baseline microbiome/metabolome signatures in longer trials.
BACKGROUND: On the basis of the contribution of the gut microbiota to hypertension development, a novel strategy involving fecal microbiota transplantation (FMT) has been proposed to treat hypertension, but its efficacy has not been investigated in the clinic. METHODS: In a randomized, blinded, placebo-controlled clinical trial (2021/03-2021/12, ClinicalTrials.gov, NCT04406129), hypertensive patients were recruited from seven centers in China, and received FMT or placebo capsules orally at three visits. The patients were randomized at a 1:1 ratio in blocks of four and stratified by center by an independent statistician. The intention-to-treat principle was implemented, as all randomized participants who received at least one intervention were included. The primary outcome was the decrease in office systolic blood pressure (SBP) from baseline to the day 30 visit. Adverse events (AEs) were recorded through the 3-month follow-up to assess safety measures. Alterations in BP, the fecal microbiome, and the plasma metabolome were assessed via exploratory analyses. RESULTS: This study included 124 patients (mean age 43 years, 73.4% men) who received FMT (n=63) or placebo (n=61) capsules. The numbers of participants who experienced AEs (13 (20.6%) vs. 9 (14.8%), p=0.39) and the primary outcome (6.28 (11.83) vs. 5.77 (10.06) mmHg, p=0.62) were comparable between the groups. The FMT group presented a decrease in SBP after 1 week of FMT, with a between-arm difference of -4.34 (95% CI, -8.1 to -0.58; p=0.024) mmHg, but this difference did not persist even after repeated intervention. After FMT, shifts in microbial richness and structure were identified and the abundance of the phyla Firmicutes and Bacteroidetes was altered. Decreases in the abundances of Eggerthella lenta, Erysipelatoclostridium ramosum, Anaerostipes hadrus, Gemella haemolysans, and Streptococcus vestibularis and increases in the abundances of Parabacteroides merdae, Prevotella copri, Bacteroides galacturonicus, Eubacterium sp. CAG 180, Desulfovibrio piger, Megamonas hypermegale, Collinsella stercoris, Coprococcus catus, and Allisonella histaminiformans were identified and correlated with office SBP. Those species were also correlated with responding and inversely office SBP-associated metabolites including tyrosine, glutamine, aspartate, phenylalanine, methionine, serine, sarcosine, and/or asparagine. CONCLUSIONS: Safety but unsustainable BP reduction was observed in the first trial of the effects of FMT on hypertension. Additional intervention studies on specific microbes with metabolite-targeting and BP-modulating features are needed. Video Abstract.
3. Systolic blood pressure lower than 130 mmHg in heart failure with preserved ejection fraction: a systematic review and meta-analysis of clinical outcomes.
Across six RCTs where intervention groups achieved SBP <130 mmHg, HF hospitalizations were reduced (RR 0.80, p=0.005) with a trend toward lower all-cause mortality, at the expense of more hypotension but no increase in renal dysfunction or serious adverse events.
Impact: This synthesis aligns BP targets with improved outcomes in HFpEF and informs forthcoming guidelines, despite indirectness from interventions not exclusively targeting SBP <130 mmHg.
Clinical Implications: In HFpEF, manage SBP to <130 mmHg when tolerated, with vigilant monitoring for hypotension, while anticipating no excess renal or serious adverse events based on current evidence.
Key Findings
- Achieving SBP <130 mmHg reduced HF hospitalizations (RR 0.80, 95% CI 0.69–0.93; p=0.005).
- Trend toward lower all-cause mortality (RR 0.74, 95% CI 0.53–1.04; p=0.083).
- Hypotension increased (RR 1.35, 95% CI 1.03–1.79; p=0.03) without increases in renal dysfunction or serious adverse events.
Methodological Strengths
- PRISMA-consistent systematic search including RCTs with ≥6-month follow-up.
- Consistent direction of effects across heterogeneous interventions achieving SBP <130 mmHg.
Limitations
- Indirectness: no RCTs that randomized patients specifically to SBP <130 mmHg as the primary intervention.
- Potential heterogeneity in populations, interventions, and BP measurement protocols.
Future Directions: Conduct pragmatic RCTs targeting SBP <130 mmHg with standardized BP protocols in HFpEF, including frailty and orthostatic hypotension assessments, and evaluate patient-centred outcomes.
The optimal blood pressure (BP) management level for patients with heart failure (HF) with preserved ejection fraction (HFpEF) remains unclear. In conjunction with the upcoming the Japanese Society of Hypertension Guidelines for the Management of Hypertension 2025 (JSH2025), we conducted a systematic review and meta-analysis to evaluate whether managing systolic BP (SBP) < 130 mmHg improves outcomes in HFpEF patients. We searched PubMed, Cochrane and Ichishi for randomized controlled trials (RCTs) published since 2012 that targeted HFpEF patients; used strict BP control, antihypertensive medications, or intensive HF management as interventions; demonstrated significant BP reduction with achieved SBP < 130 mmHg in intervention groups; and had follow-up periods ≥6 months. Six studies were included, evaluating mineralocorticoid receptor antagonists (n = 2), angiotensin receptor-neprilysin inhibitors (n = 2), intensive BP control (n = 1), and intensive HF management (n = 1). Meta-analysis showed that achieving SBP < 130 mmHg significantly reduced HF hospitalizations (relative risk [RR] [95% confidence interval (CI)] 0.80 [0.69-0.93], p = 0.005) and demonstrated a trend toward reduced all-cause mortality (RR [95% CI] 0.74 [0.53-1.04], p = 0.083). While hypotension increased (RR [95% CI] 1.35 [1.03-1.79], p = 0.03), there was no significant increase in renal dysfunction or serious adverse events. Despite limitations from indirectness (no RCTs specifically targeted SBP < 130 mmHg as primary intervention), our findings suggest that achieving SBP < 130 mmHg in HFpEF patients may improve clinical outcomes. We recommend managing HFpEF patients to achieve SBP < 130 mmHg, while carefully monitoring for hypotension.