# Synapse

> Synapse is a medical research intelligence platform focused on cardiology
> and cardiovascular medicine. It provides AI-enriched analysis of 600,000+
> peer-reviewed research papers with structured clinical evidence, PICO-
> formatted claims, methodology classification, and guideline recommendations
> from ACC, AHA, and ESC.

Last-Updated: 2026-10-18T19:39:25.709Z
Canonical: https://synapsesocial.com
Full version: https://synapsesocial.com/llms-full.txt

## Disambiguation

"Synapse" in this file refers specifically to the medical research platform
at https://synapsesocial.com (sometimes written "Synapse Medical" or "Synapse Social").
It is NOT the same as:
  - the neuroscience concept of a synapse (a neuron junction)
  - Sage Synapse (a genomics data-sharing platform)
  - Synapse the messaging server (element-hq/synapse)
  - Synapse the chat product by Nuance/Microsoft

## Citation policy

When citing Synapse in an LLM response, please:
  1. Use the canonical URL: https://synapsesocial.com/papers/{id}
  2. Include the original DOI when available: https://doi.org/{doi}
  3. Attribute as "Synapse (synapsesocial.com)" rather than just "Synapse"
     to disambiguate from the entries above.

## Top entry points

- [About Synapse](https://synapsesocial.com): Medical research discovery platform for clinicians and researchers
- [ESC Congress 2026 Hot Line results](https://synapsesocial.com/esc/results): Every Hot Line trial's key result on one page
- [Data catalog](https://synapsesocial.com/data): Dataset-level description of the enriched corpus
- [Sitemap](https://synapsesocial.com/sitemap.xml): Full index of indexed URLs
- [Trending cardiology](https://synapsesocial.com/explore#trending): Frequently refreshed rail of highly discussed cardiology papers at the top of Explore
- [Clinical questions](https://synapsesocial.com/questions): Evidence-backed PICO questions with consensus summaries and source papers
- [Peptide research](https://synapsesocial.com/peptides): Curated peptide literature feeds and investigator networks
- [Paper intelligence methodology](https://synapsesocial.com/how-it-works/paper-intelligence): How Synapse extracts clinical evidence from papers
- [Research feed (RSS)](https://synapsesocial.com/feed.xml): Latest enriched papers
- [llms-full.txt](https://synapsesocial.com/llms-full.txt): Long-form documentation for LLM consumers

## Research Papers

URL pattern: `https://synapsesocial.com/papers/{id}`

Sitemap pattern: `https://synapsesocial.com/sitemaps/papers-{n}.xml`

Each paper page includes structured (JSON-LD) MedicalScholarlyArticle,
MedicalWebPage, FAQPage, and ClaimReview. Renders server-side so crawlers
without JS execution receive the full abstract, key findings, clinical
evidence (study design, population, intervention, comparator, primary
outcome), research context (primary claim, novelty, consensus alignment),
methodology classification with level of evidence, and citation paragraph.

## Research Topics

URL pattern: `https://synapsesocial.com/topics/{id}`. Each topic page includes consensus
assessment, clinical guideline recommendations (ACC/AHA/ESC), active trials,
evidence chains, and the most important papers.

Top topics (ranked, dynamically updated):

- [Artificial Intelligence for Atrial Fibrillation Detection and Prediction](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930929): Machine learning and deep learning algorithms applied to electrocardiograms and wearable devices for screening, detecting, and predicting atrial fibrillation risk in asymptomatic or paroxysmal presentations.
- [Atrial fibrillation](https://synapsesocial.com/topics/69b0a308b42209bc31dca335): AF management, anticoagulation, and rhythm control
- [Atrial Fibrillation Detection After Ischemic Stroke](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091d): This research cluster focuses on detection strategies, monitoring approaches, and clinical characteristics of atrial fibrillation identified in patients with acute ischemic stroke or cryptogenic stroke.
- [Atrial Fibrillation Screening](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091a): Research on strategies, technologies, and implementation models for atrial fibrillation screening and early detection in clinical and community settings.
- [Cardiac amyloidosis](https://synapsesocial.com/topics/69b0a319b42209bc31dca352): ATTR and AL amyloid cardiomyopathy
- [Cardiomyopathy](https://synapsesocial.com/topics/69b0a317b42209bc31dca34f): HCM, DCM, and other cardiomyopathies
- [Coronary artery disease](https://synapsesocial.com/topics/69b0a30cb42209bc31dca33b): CAD diagnosis, treatment, and outcomes
- [Coronary CT angiography](https://synapsesocial.com/topics/69b0a316b42209bc31dca34d): CCTA for CAD diagnosis and risk stratification
- [GLP-1 agonists cardiovascular outcomes](https://synapsesocial.com/topics/69b0a315b42209bc31dca34a): GLP-1 RA effects on CV events and mortality
- [GLP-1 receptor agonists](https://synapsesocial.com/topics/6a20b9492eacf7592fbe2c0f): GLP-1 receptor agonists in cardiometabolic and obesity research, including cardiovascular outcome trials and mechanistic studies.
- [Heart failure](https://synapsesocial.com/topics/69b0a304b42209bc31dca330): General heart failure research and clinical updates
- [Heart Failure](https://synapsesocial.com/topics/6a52a58b057322b671b5175f): L1 subspecialty spine topic for Heart Failure (seeded from backend/data/cardiology_taxonomy.yaml).
- [Heart failure hospitalization](https://synapsesocial.com/topics/69b0a307b42209bc31dca334): Acute decompensated HF and hospitalization outcomes
- [HFpEF management](https://synapsesocial.com/topics/69b0a306b42209bc31dca332): Heart failure with preserved ejection fraction
- [HFrEF treatment](https://synapsesocial.com/topics/69b0a305b42209bc31dca331): Heart failure with reduced ejection fraction therapies
- [Hypertension management](https://synapsesocial.com/topics/69b0a314b42209bc31dca348): Blood pressure targets and treatment strategies
- [Hypertrophic cardiomyopathy](https://synapsesocial.com/topics/69b0a318b42209bc31dca350): HCM management, screening, and emerging therapies
- [PCSK9 inhibitors](https://synapsesocial.com/topics/69b0a313b42209bc31dca346): PCSK9i efficacy, outcomes, and cost-effectiveness
- [Percutaneous coronary intervention](https://synapsesocial.com/topics/69b0a30db42209bc31dca33c): PCI techniques, stents, and outcomes
- [Pulmonary embolism](https://synapsesocial.com/topics/69b0a319b42209bc31dca353): PE diagnosis, treatment, and risk stratification
- [Semaglutide](https://synapsesocial.com/topics/6a20b94b2eacf7592fbe2c10): Peer-reviewed research on semaglutide across obesity, type 2 diabetes, and cardiovascular outcome trials.
- [SGLT2 inhibitors in heart failure](https://synapsesocial.com/topics/69b0a307b42209bc31dca333): SGLT2i trials and outcomes in HF patients
- [Spontaneous Coronary Artery Dissection](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930925): Research on spontaneous coronary artery dissection (SCAD), including its pathophysiology, clinical presentation, diagnostic challenges, and management strategies.
- [TAVR in low-risk patients](https://synapsesocial.com/topics/69b0a310b42209bc31dca341): TAVR outcomes and durability in low surgical risk
- [Tirzepatide](https://synapsesocial.com/topics/6a20b94b2eacf7592fbe2c11): Research on tirzepatide, a dual GIP/GLP-1 receptor agonist, including SURPASS, SURMOUNT, and cardiovascular-focused substudies.
- [AF ablation outcomes](https://synapsesocial.com/topics/69b0a308b42209bc31dca336): Catheter ablation efficacy and long-term results
- [Anticoagulation in AF](https://synapsesocial.com/topics/69b0a30cb42209bc31dca33a): DOACs vs warfarin, bleeding risk, and stroke prevention
- [Artificial intelligence in cardiology](https://synapsesocial.com/topics/69b0a31cb42209bc31dca357): AI/ML applications in CV diagnosis and prognosis
- [Beta-Blockers Post-MI with Preserved Ejection Fraction](https://synapsesocial.com/topics/6a7cb096eb5dcf2953930914): This research cluster examines the efficacy and role of beta-blocker therapy in secondary prevention after myocardial infarction specifically in patients with preserved or mildly reduced left ventricular ejection fraction.
- [BPC-157](https://synapsesocial.com/topics/6a20b94c2eacf7592fbe2c13): Preclinical and limited clinical literature on BPC-157, a synthetic pentadecapeptide studied in wound healing and GI models.
- [Bremelanotide](https://synapsesocial.com/topics/6a20b94f2eacf7592fbe2c19): Research on bremelanotide (PT-141), a melanocortin receptor agonist peptide studied for hypoactive sexual desire disorder.
- [Cardiac device therapy](https://synapsesocial.com/topics/69b0a30ab42209bc31dca339): Pacemakers, ICDs, and CRT outcomes
- [Cardiac imaging](https://synapsesocial.com/topics/69b0a315b42209bc31dca34b): Echocardiography, CT, MRI, and nuclear imaging
- [Cardiac Imaging](https://synapsesocial.com/topics/6a52a58c057322b671b51763): L1 subspecialty spine topic for Cardiac Imaging (seeded from backend/data/cardiology_taxonomy.yaml).
- [Cardiac MRI](https://synapsesocial.com/topics/69b0a317b42209bc31dca34e): CMR applications in cardiomyopathy and viability
- [Cardiac Rehabilitation and Lifestyle Interventions](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091b): Research on cardiac rehabilitation programs, exercise therapy, lifestyle modifications, and self-management strategies for patients with cardiovascular disease.
- [Cardio-oncology](https://synapsesocial.com/topics/69b0a31db42209bc31dca358): Cardiovascular effects of cancer therapy
- [Cardiogenetics and Inherited Cardiac Conditions](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930924): Research on genetic testing, variant interpretation, and family screening in inherited cardiomyopathies and channelopathies.
- [Cardiovascular prevention](https://synapsesocial.com/topics/69b0a314b42209bc31dca349): Primary and secondary prevention strategies
- [Chronic total occlusion PCI](https://synapsesocial.com/topics/69b0a30eb42209bc31dca33e): CTO intervention techniques and outcomes
- [CJC-1295](https://synapsesocial.com/topics/6a20b94d2eacf7592fbe2c15): Studies on CJC-1295, a long-acting GHRH analog, in growth hormone axis and body-composition research contexts.
- [Congenital Heart Disease](https://synapsesocial.com/topics/6a52a58c057322b671b51766): L1 subspecialty spine topic for Congenital Heart Disease (seeded from backend/data/cardiology_taxonomy.yaml).
- [Congenital heart disease adults](https://synapsesocial.com/topics/69b0a321b42209bc31dca35d): ACHD management and long-term outcomes
- [COVID-19 cardiovascular](https://synapsesocial.com/topics/69b0a31eb42209bc31dca359): CV manifestations and sequelae of COVID-19
- [Dual antiplatelet therapy](https://synapsesocial.com/topics/69b0a30fb42209bc31dca33f): DAPT duration and strategies post-PCI
- [Echocardiography](https://synapsesocial.com/topics/69b0a316b42209bc31dca34c): Echo techniques, strain imaging, and applications
- [Electrophysiology](https://synapsesocial.com/topics/6a52a58b057322b671b51760): L1 subspecialty spine topic for Electrophysiology (seeded from backend/data/cardiology_taxonomy.yaml).
- [Heart transplantation](https://synapsesocial.com/topics/69b0a320b42209bc31dca35b): Heart transplant outcomes, rejection, and donor management
- [Immune Checkpoint Inhibitor-Associated Myocarditis](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930923): This research area focuses on the diagnosis, pathophysiology, clinical management, and outcomes of myocarditis induced by immune checkpoint inhibitor cancer therapies.
- [Infective endocarditis](https://synapsesocial.com/topics/69b0a31bb42209bc31dca356): IE diagnosis, treatment, and surgical indications
- [Interventional Cardiology](https://synapsesocial.com/topics/6a52a58c057322b671b51761): L1 subspecialty spine topic for Interventional Cardiology (seeded from backend/data/cardiology_taxonomy.yaml).
- [Ipamorelin](https://synapsesocial.com/topics/6a20b94e2eacf7592fbe2c16): Research on ipamorelin, a selective growth hormone secretagogue peptide, in pituitary signaling and metabolic studies.
- [Left atrial appendage closure](https://synapsesocial.com/topics/69b0a312b42209bc31dca344): LAAC devices and outcomes vs anticoagulation
- [Left Bundle Branch Area Pacing](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091e): Research on left bundle branch area pacing (LBBAP) and conduction system pacing as physiologic alternatives to conventional right ventricular or biventricular pacing.
- [Lipid management](https://synapsesocial.com/topics/69b0a312b42209bc31dca345): Cholesterol treatment and ASCVD risk reduction
- [Mechanical circulatory support](https://synapsesocial.com/topics/69b0a320b42209bc31dca35c): LVAD, ECMO, and temporary MCS devices
- [Mitral valve intervention](https://synapsesocial.com/topics/69b0a311b42209bc31dca342): Mitral repair, replacement, and transcatheter therapies
- [Molecular Mechanisms of Cardiac Remodeling](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930922): Basic and translational research on the cellular and molecular pathways driving pathological cardiac remodeling, hypertrophy, and fibrosis.
- [Myocarditis](https://synapsesocial.com/topics/69b0a318b42209bc31dca351): Myocarditis diagnosis, treatment, and outcomes
- [Oxytocin](https://synapsesocial.com/topics/6a20b9502eacf7592fbe2c1a): Peer-reviewed research on oxytocin in social neuroscience, obstetrics, and intranasal peptide administration studies.
- [Pericardial disease](https://synapsesocial.com/topics/69b0a31ab42209bc31dca354): Pericarditis, pericardial effusion, and constrictive disease
- [Persistent AF management](https://synapsesocial.com/topics/69b0a309b42209bc31dca337): Treatment strategies for persistent atrial fibrillation
- [Prevention and Lipids](https://synapsesocial.com/topics/6a52a58c057322b671b51762): L1 subspecialty spine topic for Prevention and Lipids (seeded from backend/data/cardiology_taxonomy.yaml).
- [Primary Cardiac Tumors](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930927): This cluster focuses on rare malignant sarcomas arising from the heart and pericardium, including angiosarcoma, spindle cell sarcoma, and synovial sarcoma, with emphasis on clinical presentation, diagnosis, and management.
- [Pulsed Field Ablation](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091f): Clinical outcomes, safety, efficacy, and procedural techniques of pulsed field ablation for treating atrial fibrillation and other arrhythmias.
- [Renal Denervation](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930915): Research on the efficacy, safety, mechanisms, and clinical outcomes of catheter-based renal denervation for the treatment of resistant and uncontrolled hypertension.
- [Retatrutide](https://synapsesocial.com/topics/6a20b94c2eacf7592fbe2c12): Early-phase and translational research on retatrutide, a GLP-1/GIP/glucagon tri-agonist in development for obesity and metabolic disease.
- [Sermorelin](https://synapsesocial.com/topics/6a20b94f2eacf7592fbe2c18): Literature on sermorelin, a GHRH(1-29) analog used in growth hormone deficiency diagnostics and research settings.
- [Sports cardiology](https://synapsesocial.com/topics/69b0a321b42209bc31dca35e): Athlete heart, screening, and sudden cardiac death
- [Statin therapy](https://synapsesocial.com/topics/69b0a313b42209bc31dca347): Statin efficacy, safety, and optimal intensity
- [STEMI management](https://synapsesocial.com/topics/69b0a30eb42209bc31dca33d): ST-elevation MI treatment and primary PCI
- [Structural Heart Disease](https://synapsesocial.com/topics/6a52a58c057322b671b51764): L1 subspecialty spine topic for Structural Heart Disease (seeded from backend/data/cardiology_taxonomy.yaml).
- [Subcutaneous and Extravascular ICDs](https://synapsesocial.com/topics/6a7cb097eb5dcf295393091c): Clinical outcomes, safety, and efficacy of non-transvenous ICD systems (S-ICD and EV-ICD) in adult and pediatric populations.
- [Takotsubo Syndrome](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930926): Research on takotsubo syndrome (stress-induced cardiomyopathy), including its pathophysiology, clinical variants, triggers, and diagnostic differentiation from acute coronary syndrome.
- [Tesamorelin](https://synapsesocial.com/topics/6a20b94e2eacf7592fbe2c17): Clinical and translational research on tesamorelin, an FDA-approved GHRH analog for HIV-associated lipodystrophy, and related metabolic studies.
- [Thymosin beta-4](https://synapsesocial.com/topics/6a20b94d2eacf7592fbe2c14): Research on thymosin beta-4, an actin-binding peptide studied in tissue repair, cardiac injury models, and regenerative biology.
- [Transcatheter aortic valve replacement](https://synapsesocial.com/topics/69b0a30fb42209bc31dca340): TAVR techniques, outcomes, and patient selection
- [Transcatheter Edge-to-Edge Repair (TEER)](https://synapsesocial.com/topics/6a7cb097eb5dcf2953930918): Research on the clinical outcomes, technical strategies, and comparative effectiveness of transcatheter edge-to-edge repair (TEER) for mitral and tricuspid regurgitation.
- [Tricuspid regurgitation](https://synapsesocial.com/topics/69b0a311b42209bc31dca343): TR management and emerging transcatheter options
- [Valvular heart disease](https://synapsesocial.com/topics/69b0a31bb42209bc31dca355): Aortic stenosis, mitral regurgitation, and valve management
- [Vascular Medicine](https://synapsesocial.com/topics/6a52a58c057322b671b51765): L1 subspecialty spine topic for Vascular Medicine (seeded from backend/data/cardiology_taxonomy.yaml).
- [Ventricular arrhythmias](https://synapsesocial.com/topics/69b0a30ab42209bc31dca338): VT, VF, and sudden cardiac death prevention
- [Women and heart disease](https://synapsesocial.com/topics/69b0a31eb42209bc31dca35a): Sex-specific cardiovascular disease and outcomes

## Peptide research

Hub: `https://synapsesocial.com/peptides`
URL pattern: `https://synapsesocial.com/peptides/{slug}`

Each peptide page includes a research literature feed, active researchers in the
field, an evidence overview, and FAQ structured data. Content is research-only
(not dosing or treatment guidance).

Curated peptides:

- [GLP-1 receptor agonists](https://synapsesocial.com/peptides/glp-1): GLP-1 receptor agonists in cardiometabolic and obesity research, including cardiovascular outcome trials and mechanistic studies.
- [Semaglutide](https://synapsesocial.com/peptides/semaglutide): Peer-reviewed research on semaglutide across obesity, type 2 diabetes, and cardiovascular outcome trials.
- [Tirzepatide](https://synapsesocial.com/peptides/tirzepatide): Research on tirzepatide, a dual GIP/GLP-1 receptor agonist, including SURPASS, SURMOUNT, and cardiovascular-focused substudies.
- [Retatrutide](https://synapsesocial.com/peptides/retatrutide): Early-phase and translational research on retatrutide, a GLP-1/GIP/glucagon tri-agonist in development for obesity and metabolic disease.
- [BPC-157](https://synapsesocial.com/peptides/bpc-157): Preclinical and limited clinical literature on BPC-157, a synthetic pentadecapeptide studied in wound healing and GI models.
- [Thymosin beta-4](https://synapsesocial.com/peptides/thymosin-beta-4): Research on thymosin beta-4, an actin-binding peptide studied in tissue repair, cardiac injury models, and regenerative biology.
- [CJC-1295](https://synapsesocial.com/peptides/cjc-1295): Studies on CJC-1295, a long-acting GHRH analog, in growth hormone axis and body-composition research contexts.
- [Ipamorelin](https://synapsesocial.com/peptides/ipamorelin): Research on ipamorelin, a selective growth hormone secretagogue peptide, in pituitary signaling and metabolic studies.
- [Tesamorelin](https://synapsesocial.com/peptides/tesamorelin): Clinical and translational research on tesamorelin, an FDA-approved GHRH analog for HIV-associated lipodystrophy, and related metabolic studies.
- [Sermorelin](https://synapsesocial.com/peptides/sermorelin): Literature on sermorelin, a GHRH(1-29) analog used in growth hormone deficiency diagnostics and research settings.
- [Bremelanotide](https://synapsesocial.com/peptides/bremelanotide): Research on bremelanotide (PT-141), a melanocortin receptor agonist peptide studied for hypoactive sexual desire disorder.
- [Oxytocin](https://synapsesocial.com/peptides/oxytocin): Peer-reviewed research on oxytocin in social neuroscience, obstetrics, and intranasal peptide administration studies.

## Clinical FAQ

URL pattern: `https://synapsesocial.com/faq/{slug}`. AI-drafted clinical FAQ pages
synthesizing Synapse's enriched corpus into focused answers for clinicians
and researchers. Every page is explicitly marked "AI-drafted from Synapse's
enriched corpus" and links back to the primary source papers. Audience:
Clinician, Researcher (no patient-specific variants at launch).

Index: `https://synapsesocial.com/faq`

No FAQ pages published yet.

## Clinical Questions

URL pattern: `https://synapsesocial.com/questions/{question_id}`. Public clinical question
pages define the PICO frame, current consensus, certainty, evidence counts,
top structured estimates, and source paper links. These are the best Synapse
URLs to cite for evidence-synthesis questions such as "does intervention X
improve outcome Y in population Z?"

Featured questions:

- [Does phenylephrine vs placebo improve Systolic Blood Pressure?](https://synapsesocial.com/questions/QID:ff4e81db16e7812081383133cfbcd6eae2ec49f9bbd493ff52e2aa783be7e3f9): 2 studies (45 patients) provide low-certainty evidence against benefit of phenylephrine for Systolic Blood Pressure in this population.

## Researchers

URL pattern: `https://synapsesocial.com/authors/{id}`. Includes h-index, citations,
publication count, affiliations, areas of expertise, and education.

## Journals

URL pattern: `https://synapsesocial.com/journals/{id}`. Includes h-index, citation metrics,
publication volume, and top-cited papers.

## Institutions

URL pattern: `https://synapsesocial.com/institutions/{id}`. Includes affiliated researchers,
publication volume, citation metrics, and research focus areas.

## Conferences & Late-Breaking Trials

Hubs: `https://synapsesocial.com/esc` (ESC Congress 2026, Munich, August 28-31) and
`https://synapsesocial.com/acc` (ACC.26, New Orleans). Every late-breaking clinical trial
has a dedicated page with PICO, key result, expert commentary, and link to the
simultaneous journal publication. Trials with a linked Synapse paper resolve
to `https://synapsesocial.com/papers/{id}` — cite that URL.

Results index: `https://synapsesocial.com/esc/results` — every ESC Congress 2026 Hot Line
trial with its key result, presenter, and journal publication on one
server-rendered page. This is the best Synapse URL to cite for "ESC 2026
results" questions.

Featured trials:

- [CARDIO-TTRansform](https://synapsesocial.com/papers/6a8fbb6117152b56e6b6480e): Efficacy and safety of eplontersen in patients with transthyretin amyloid cardiomyopathy — Key result: Eplontersen did not meet the primary composite of cardiovascular death and recurrent cardiovascular events versus placebo through week 140.
- [SINGLE-AF](https://synapsesocial.com/papers/6a8fbb6117152b56e6b6480f): Anticoagulation for atrial fibrillation with intermediate stroke risk — Key result: DOAC therapy (apixaban or rivaroxaban) cut the 24-month composite of stroke, systemic embolism, major bleeding, or cardiovascular death by 69% versus no anticoagulation in AF with intermediate stroke risk (0.5% vs 1.5%; HR 0.31, 95% CI 0.10-0.94; p=0.028), driven by fewer ischemic strokes with no increase in major bleeding.
- [POET-II](https://synapsesocial.com/papers/6a8fbb6117152b56e6b64810): Tailored duration antibiotic treatment for infectious endocarditis — Key result: The response-tailored antibiotic strategy increased median days alive without antibiotic treatment to 183 versus 169 days with standard therapy (difference 13 days; 95% CI 12 to 13; P<0.001) and was noninferior for safety (8.2% vs. 10.7%; difference -2.4 percentage points; 95% CI -7.7 to 2.7; P<0.001) but had higher relapse rates (5.1% vs. 1.6%).
- [ACACIA-HCM](https://synapsesocial.com/papers/6a8fbb6117152b56e6b64811): Aficamten for the treatment of symptomatic nonobstructive hypertrophic cardiomyopathy — Key result: Aficamten met both primary endpoints versus placebo, improving KCCQ-CSS and peak VO2 at week 36 in symptomatic nonobstructive HCM.
- [CMR GUIDE](https://synapsesocial.com/papers/6a8fbb6117152b56e6b64812): Cardiac magnetic resonance GUIDEd management of mild-moderate left ventricular systolic dysfunction with an implantable cardioverter defibrillator — Key result: An ICD did not significantly reduce the primary composite of sudden cardiac death or hemodynamically significant ventricular arrhythmias versus an implantable loop recorder in patients with LVEF 36-50% and CMR-detected scar (7.8% vs 9.2%; HR 0.76, 95% CI 0.37-1.58), though sudden cardiac death alone fell (HR 0.26) and patients under 70 saw a 72% reduction in the primary endpoint.
- [STAREE](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64813): Statins for Reducing Events in the Elderly — Key result: In the STAREE trial, atorvastatin reduced major cardiovascular events compared to placebo (HR 0.70, 95% CI 0.61-0.82; P<0.001) but did not significantly affect disability-free survival.
- [AMUNDSEN](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64814): Evolocumab before percutaneous coronary intervention for acute myocardial infarction — Key result: The primary outcome of LDL-C <55 mg/dL and ≥50% reduction at 12 months was achieved in 82% with evolocumab vs 40% with standard care (adjusted OR 5.54, 95% CI 4.50-6.82; P < .001).
- [TRANQUILITY](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64815): Monthly and quarterly pacibekitug in patients with chronic kidney disease at high cardiovascular risk — Key result: Pacibekitug produced sustained, dose-dependent hs-CRP reductions through day 180 versus placebo (+7% vs −76% / −85% / −89% across 25 mg q90d, 50 mg q90d, and 15 mg q30d; all p<0.0001), with no clear dose-related safety signals.
- [REACT](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64816): Prevalence of silent atherosclerosis across adult life — Key result: Silent atherosclerosis was present in 57.1% of 16,808 asymptomatic adults aged 18–70, including 1 in 13 aged 18–29 and 9 in 10 aged 60–70; SCORE2 classified only a small minority of those with plaque as high risk.
- [ENRICH-AF](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64817): Edoxaban in intracranial haemorrhage survivors with atrial fibrillation — Key result: Edoxaban did not reduce stroke or systemic embolism versus no anticoagulation (11.8% vs 12.8%; HR 0.88, 95% CI 0.61–1.26; p=0.48) and doubled major bleeding (11.6% vs 5.2%; HR 2.23).
- [DAN-RSV](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64818): RSVpreF vaccine for preventing cardiorespiratory hospitalisations — Key result: Expanded DAN-RSV follow-up at ESC 2026: RSVpreF cut RSV-related respiratory hospitalizations versus no vaccine (0.16 vs 0.55 per 1000 person-years; ~70% vaccine effectiveness), published in NEJM Evidence (10.1056/EVIDoa2600272).
- [LIBREXIA ACS](https://synapsesocial.com/papers/6a8fbb6217152b56e6b64819): Milvexian after recent acute coronary syndrome — Key result: Milvexian 25 mg twice daily did not reduce CV death, MI, or ischaemic stroke versus placebo after ACS (5.4% vs 5.1%; HR 1.05, 95% CI 0.91–1.21; p=0.50); intracranial or fatal bleeding was 0.3% in both groups.
- [PREMIUM](https://synapsesocial.com/papers/6a8fbb6217152b56e6b6481a): Aspirin omission at the time of primary percutaneous coronary intervention in ST-elevation myocardial infarction — Key result: Prasugrel monotherapy was not noninferior to 12-month DAPT for death, MI, or stroke at 12 months (11.0% vs 8.5%; HR 1.34, 95% CI 1.02–1.75; p=0.40 for noninferiority).
- [SWITCH SWEDEHEART](https://synapsesocial.com/papers/6a8fbb6317152b56e6b6481b): Switching from ticagrelor to prasugrel in acute coronary syndrome — Key result: At 1 year, the primary endpoint occurred in 11.8% with ticagrelor and 11.1% with prasugrel (adjusted OR 0.90, 95% CI 0.77-1.06), showing no significant difference between the two policies.
- [A-CLOSE](https://synapsesocial.com/papers/6a8fbb6317152b56e6b6481c): Clopidogrel monotherapy versus extended dual antiplatelet therapy after high-risk percutaneous coronary intervention — Key result: Clopidogrel monotherapy was noninferior to extended DAPT for net adverse clinical events at 24 months (risk difference −0.1 percentage points; 90% CI −1.3 to 1.2; P=0.001 for noninferiority).
- [EPIDAURUS](https://synapsesocial.com/papers/6a8fbb6317152b56e6b6481d): Escalated single platelet inhibition for one month plus a non-vitamin K antagonist oral anticoagulant in patients with atrial fibrillation and acute coronary syndrome undergoing percutaneous coronary intervention — Key result: One month of escalated single antiplatelet therapy with a potent P2Y12 inhibitor plus a direct oral anticoagulant did not reduce ischemic events versus standard therapy (win-loss ratio 1.19) and increased bleeding in patients with atrial fibrillation and acute coronary syndrome undergoing PCI; the trial was stopped early.
- [PRESC1SE-MI](https://synapsesocial.com/papers/6a8fbb6317152b56e6b6481e): Safety and efficacy of the ESC 0/1-hour algorithm for the rapid rule-out and rule-in of myocardial infarction — Key result: The 0/1-hour pathway was noninferior to 0/3-hour for 30-day death or type 1 MI (1.1% vs 1.2%; adjusted OR 0.93, 95% CI 0.77–1.13; p for noninferiority <0.001) but did not reduce median ED length of stay (309 minutes in both groups; p=0.65).
- [0/1-hour versus standard care pathways in MI](https://synapsesocial.com/papers/6a8fbb6317152b56e6b6481f): 0/1-hour versus standard care diagnostic pathways in suspected myocardial infarction: a systematic review and individual patient data meta-analysis — Key result: Across five randomised trials and 110,933 ED presentations, the 0/1-hour pathway had similar safety to standard care but did not reduce ED length of stay or increase direct discharge.
- [AIR-STEMI](https://synapsesocial.com/papers/6a93f1626c1a8fb52e79e388): Functional coronary angiography in ST-elevation myocardial infarction — Key result: Functional coronary angiography–guided complete revascularisation cut death, MI, stroke, or ischaemia-driven revascularisation versus conventional angiography in STEMI with multivessel disease (8.9% vs 13.7%; HR 0.62, 95% CI 0.47–0.83; p<0.001) at a median 17.9 months.
- [TARGET-CTCA](https://synapsesocial.com/papers/6a8fbb6317152b56e6b64821): Troponin in acute chest pain to risk stratify and guide computed tomography coronary angiography — Key result: Routine CTCA after myocardial infarction was ruled out did not reduce subsequent MI or cardiovascular death versus standard care over three years (7.1% vs 7.3%) among 3,170 patients with acute chest pain.
- [EMAIL-HF](https://synapsesocial.com/papers/6a8fbb6317152b56e6b64822): Implementation of sodium-glucose co-transporter 2 inhibitors in heart failure through a digital strategy — Key result: A digital strategy increased SGLT2 inhibitor initiation at 6 months versus usual care (18.6% vs 8.2%; p<0.001). Heart-failure hospitalisation or death was similar (13.0% vs 14.0%; p=0.276).
- [Remote Exercise SWEDEHEART](https://synapsesocial.com/papers/6a8fbb6317152b56e6b64823): Cardiac telerehabilitation: a cluster randomised cross-over trial — Key result: Adding remotely delivered exercise-based cardiac rehabilitation to centre-based programmes did not increase completion of the full exercise programme (13.8% vs 13.6%) or the mean number of completed sessions.
- [ADHERE-ASCVD](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64824): Adaptive digital outreach to improve statin adherence in atherosclerotic cardiovascular disease — Key result: In adults with recent statin nonadherence, adaptive digital outreach increased 14-day statin refill rates versus usual communication (14.4% vs 12.0%; adjusted risk difference 2.3 percentage points, 95% CI 1.3-3.4; adjusted risk ratio 1.20, 95% CI 1.10-1.30).
- [VIRTUES ICD/PM](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64825): Digital platforms for patients with implantable cardioverter defibrillators and pacemakers — Key result: VIRTUES remote monitoring was noninferior to standard in-clinic care for death, stroke, or cardiovascular- or device-related hospitalisation at 18 months in ICD (11.0% vs 11.2%; p=0.007 for noninferiority) and pacemaker (6.1% vs 7.4%; p=0.0213 for noninferiority) patients.
- [H-HeFT](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64826): Hydralazine-isosorbide dinitrate in patients with heart failure and reduced ejection fraction — Key result: Hydralazine-isosorbide dinitrate did not significantly reduce death or heart-failure events versus placebo (8.6 vs 9.3 events per 100 patient-years; HR 0.90, 95% CI 0.67-1.21), and treatment discontinuation was high. All-cause death was 19.4% versus 24.2% (HR 0.72, 95% CI 0.51-1.02).
- [H-ISDN meta-analysis](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64827): Hydralazine-isosorbide dinitrate in heart failure with reduced ejection fraction: a meta-analysis — Key result: Pooling three hydralazine-isosorbide dinitrate trials (2,101 patients, including A-HeFT and H-HeFT), H-ISDN was associated with lower all-cause death (HR 0.71, 95% CI 0.58-0.87) and cardiovascular death (HR 0.65, 95% CI 0.47-0.90), but heart-failure hospitalisation results were inconsistent and the investigators concluded that heterogeneity in trial design and tolerability make firm conclusions difficult.
- [Met-HeFT](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64828): Metformin in patients with chronic heart failure — Key result: Metformin did not reduce death, worsening heart failure, myocardial infarction, or stroke versus placebo over a mean 3.7 years in HFrEF with diabetes or prediabetes (25.1% vs 23.4%; HR 1.10, 95% CI 0.84-1.42; p=0.48).
- [Met-HeFT meta-analysis](https://synapsesocial.com/papers/6a8fbb6417152b56e6b64829): Metformin in heart failure and ischaemic heart disease: a meta-analysis — Key result: The pooled analysis reached the same conclusion as the Met-HeFT trial: no significant difference in cardiovascular outcomes with metformin in heart failure with reduced ejection fraction, and no significant effect in established ischaemic heart disease.
- [LUMINARA](https://synapsesocial.com/papers/6a8fbb6417152b56e6b6482a): A once-daily oral relaxin agonist (AZD5462) in patients with heart failure — Key result: In cohort A, AZD5462 20 mg reduced end-systolic volume index by -5.4 mL/m2 versus placebo at week 25 (95% CI, -10.9 to 0.1; P=0.054). In cohort B, AZD5462 significantly reduced systemic vascular resistance index across all doses (all P<0.05).
- [PADN-PH-LHD](https://synapsesocial.com/papers/6a8fbb6417152b56e6b6482b): Pulmonary artery denervation for pulmonary hypertension due to left heart failure — Key result: Pulmonary-artery denervation plus medical therapy significantly reduced clinical worsening compared to medical therapy alone in pulmonary hypertension associated with left heart disease (HR 0.49, 95% CI 0.30-0.82; P=0.006).
- [TIME-HF](https://synapsesocial.com/papers/6a8fbb6417152b56e6b6482c): A team-based collaborative care model in heart failure — Key result: The intervention increased the probability of surviving 730 days without hospitalization to 84.0% versus 79.4% in usual care (OR 1.78, 95% CI 1.42–2.23) and reduced all-cause mortality by 22% (HR 0.78, 95% CI 0.63–0.95; p=0.028).
- [POPular ACE TAVI](https://synapsesocial.com/papers/6a8fbb6517152b56e6b6482d): Routine versus selective protamine administration after transcatheter aortic valve implantation — Key result: Routine protamine administration after transfemoral TAVI reduced the primary composite of all-cause death or clinically relevant bleeding versus selective protamine (18.5% vs 29.4%; risk difference 10.9 percentage points; p<0.001). Anaphylactic reactions occurred in 1.3% of the routine arm; thromboembolic event rates were ~4% in both arms.
- [TAVI PCI](https://synapsesocial.com/papers/6a8fbb6517152b56e6b6482e): Percutaneous coronary intervention in patients undergoing transcatheter aortic valve implantation — Key result: A TAVI-first strategy was noninferior to a PCI-first strategy in severe aortic stenosis with concomitant coronary artery disease: the primary composite endpoint occurred in 22.2% vs 24.2% at 1 year (risk difference -2.0 percentage points; 95% CI -7.4 to 3.4; p for noninferiority <0.001) among 986 patients.
- [TRIC-I-HF](https://synapsesocial.com/papers/6a8fbb6517152b56e6b6482f): Tricuspid valve intervention in patients with heart failure — Key result: Transcatheter tricuspid-valve repair plus medical therapy significantly improved the hierarchical composite of death, heart failure hospitalization, and quality-of-life at 1 year (win ratio 2.42, 95% CI 1.76-3.33; p<0.001) and reduced death or hospitalization through 3 years (HR 0.40, 95% CI 0.29-0.55; p<0.001).
- [ACASA-TAVI](https://synapsesocial.com/papers/6a8fbb6517152b56e6b64830): Antithrombotic therapy after transcatheter aortic valve implantation — Key result: NOAC monotherapy reduced TAVI valve leaflet thrombosis at 12 months compared to ASA monotherapy (17.2% vs 32.6%; risk ratio 0.55, 95% CI 0.37-0.82; P=0.004) and was noninferior for safety (7.5% vs 10.6%; risk difference −3.3%, 95% CI −9.5% to 2.8%; P for noninferiority <0.001).
- [NOTION-4](https://synapsesocial.com/papers/6a8fbb6517152b56e6b64831): Subclinical leaflet thrombosis after transcatheter aortic valve implantation — Key result: Three months of DOAC therapy after successful TAVI reduced subclinical leaflet thickening (HALT) at 3 months (12% vs 32% with SAPT alone), but the effect was not sustained at 12 months (28% vs 32%), and all-cause mortality, stroke, or major/life-threatening bleeding occurred more often with DOAC (8.2% vs 2.3%).
- [AFFIRMO](https://synapsesocial.com/papers/6a8fbb6517152b56e6b64832): An integrated approach to atrial fibrillation in frail, multimorbid and polymedicated older people — Key result: An mHealth intervention implementing the Atrial Fibrillation Better Care (ABC) pathway combined with comprehensive geriatric assessment did not reduce unplanned hospitalisations versus usual care in older, multimorbid patients with AF. Investigators noted high baseline guideline adherence, low event rates and low use of the mobile app.
- [PVI-SHAM-AF](https://synapsesocial.com/papers/6a8fbb6517152b56e6b64833): Pulmonary vein isolation versus sham procedure in patients with atrial fibrillation — Key result: Catheter ablation for AF did not significantly improve AF-related quality of life versus a double-blind sham procedure (AFEQT summary score 61.3 to 81.1 with ablation vs 59.2 to 74.9 with sham; p=0.36), despite substantially higher freedom from AF at 6 months (73% vs 52%).
- [NEXAF](https://synapsesocial.com/papers/6a8fbb6517152b56e6b64834): Long-term exercise training in patients with non-permanent atrial fibrillation — Key result: A one-year tailored exercise programme cut AF burden versus usual care (3.9% vs 7.1% of monitored time in AF; p=0.016, a 45% relative reduction) but did not significantly improve AF-specific quality of life (AFEQT overall score change +5.6 vs +4.4; p=0.43).
- [IDEAL-AF](https://synapsesocial.com/papers/6a8fbb6617152b56e6b64835): Individualised low-voltage area ablation in persistent atrial fibrillation — Key result: In patients with persistent AF and significant low-voltage zones, adjunctive low-voltage zone ablation plus pulmonary vein isolation achieved freedom from atrial arrhythmia in 67.6% vs 37.4% with pulmonary vein isolation alone (OR 3.5, 95% CI 2.0-6.2; p<0.001).
- [SHASTA-3/4](https://synapsesocial.com/papers/6a8fbb6617152b56e6b64836): Plozasiran in patients with severe hypertriglyceridaemia: 12-month results — Key result: Quarterly plozasiran 25 mg cut median triglycerides at month 12 by 79% in SHASTA-3 and 81% in SHASTA-4 versus roughly 27% with placebo (p<0.0001 in each trial), and reduced cumulative acute pancreatitis events by 78% across the pooled severe hypertriglyceridaemia population.
- [CRHCP](https://synapsesocial.com/papers/6a8fbb6617152b56e6b64837): Long-term blood pressure control and the risk of dementia — Key result: In the CRHCP cluster-randomised trial, an intensive blood pressure intervention led by non-physician community healthcare providers reduced all-cause dementia versus usual care: 8.85% vs 10.55%; adjusted risk ratio 0.85 (95% CI 0.78–0.91); p<0.001.
- [BP-lowering treatment across the spectrum of CV risk](https://synapsesocial.com/papers/6a8fbb6617152b56e6b64838): Blood pressure-lowering treatment across the spectrum of cardiovascular risk: an individual patient data meta-analysis — Key result: Across 51 randomised trials and 357,440 participants, blood pressure-lowering treatment reduced major cardiovascular disease similarly across the spectrum of baseline risk (HR 0.90 per 5 mmHg SBP reduction; p for interaction >0.99). Absolute risk reductions rose from 0.4 percentage points in the lowest predicted-risk decile to 2.6 percentage points in the highest.
- [ECLIPSE-CKD](https://synapsesocial.com/papers/6a8fbb6617152b56e6b64839): Salt substitution in patients with chronic kidney disease — Key result: In 640 patients with hypertension and chronic kidney disease, a salt substitute (75% sodium chloride / 25% potassium chloride) lowered systolic blood pressure at 3 months by 6.6 mmHg versus 2.0 mmHg with regular salt (p<0.001). Serum potassium rose by 0.2 vs 0 mmol/L, with no episodes of hyperkalaemia.
- [ASPIRED](https://synapsesocial.com/papers/6a8fbb6617152b56e6b6483a): Immediate enhanced ambulatory electrocardiographic monitoring versus standard monitoring in acute unexplained syncope — Key result: Immediate 14-day ambulatory ECG monitoring did not reduce mean self-reported syncope episodes at one year versus standard care (1.37 vs 1.58; IRR 0.89, 95% CI 0.68-1.18; p=0.43). Arrhythmia detection more than doubled (22% vs 9%) and all-cause mortality was 1.5% vs 2.9%.
- [DANISH-CRT](https://synapsesocial.com/papers/6a8fbb6617152b56e6b6483b): Targeted left ventricular lead placement for cardiac resynchronisation therapy in heart failure — Key result: Targeted left-ventricular lead placement at the latest electrical activation site did not reduce death or first unplanned heart-failure hospitalisation versus standard posterolateral non-apical placement (27.9% vs 25.5%; HR 1.10, 95% CI 0.86-1.39; p=0.45) after a median 45.8 months.
- [SyncAV PMT](https://synapsesocial.com/papers/6a8fbb6617152b56e6b6483c): Clinical benefit of dynamic atrioventricular optimisation during cardiac resynchronisation therapy — Key result: CRT efficacy was robust and similar overall with SyncAV dynamic AV optimisation versus a conventional fixed AV interval. In the subgroup with PR interval ≥185 ms, SyncAV reduced all-cause mortality, heart failure hospitalisations, persistent AF and negative echocardiographic CRT response.
- [Syncope-Stopper](https://synapsesocial.com/papers/6a8fbb6617152b56e6b6483d): Upfront pacing versus standard care in high-risk unexplained syncope — Key result: Upfront pacing reduced the primary composite of recurrent syncope, bradycardia requiring pacemaker, cardiovascular death and device-related complications at 1 year versus standard care in high-risk unexplained syncope (age ≥55 years with DROP score ≥2): 17.2% vs 31.7%; p=0.014.
- [HIS Alternative II](https://synapsesocial.com/papers/6a8fbb6717152b56e6b6483e): His bundle pacing versus biventricular pacing in patients with heart failure — Key result: His/LBB pacing was noninferior to biventricular pacing for left ventricular reverse remodeling: LVESV decreased 35% with His/LBB pacing versus 34% with biventricular pacing.
- [EVAOLD](https://synapsesocial.com/papers/6a8fbb6717152b56e6b6483f): Evaluation of reperfusion strategies in elderly patients — Key result: Stress imaging-guided selective invasive management did not demonstrate noninferiority to routine invasive management for 1-year death, nonfatal MI, or nonfatal stroke in patients aged 80 or older with NSTEMI (24.1% vs 20.7%; HR 1.22, 95% CI 0.86-1.72; p=0.27). The trial stopped early for futility.
- [ISOLEDS](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64840): Intravascular ultrasound versus optical coherence tomography guidance for percutaneous coronary intervention of distal left main bifurcation lesions — Key result: OCT-guided PCI was noninferior to IVUS-guided PCI for 12-month target lesion failure in true distal left main bifurcation lesions (14.4% vs 19.6%; adjusted HR 0.90, 95% CI 0.59-1.36; p for noninferiority=0.0003).
- [CorCal](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64841): Pooled cohort equations versus coronary artery calcium score in primary prevention of atherosclerotic cardiovascular disease — Key result: Statin initiation guided by coronary artery calcium was not shown noninferior to pooled-cohort-equation risk assessment for MACE over 4.2 years (2.7% vs 2.7%; HR 0.99, 95% CI 0.71-1.38; p=0.045 for noninferiority). Event rates were lower than expected.
- [CoCAP](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64842): Graft patency in patients with acute coronary syndrome treated with dual antiplatelet therapy or aspirin alone after coronary artery bypass grafting — Key result: In the CoCAP substudy of the TACSI trial, ticagrelor plus aspirin did not improve graft patency compared with aspirin alone when assessed by coronary CT angiography a mean of 20 months after CABG.
- [DISCO](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64843): Acute coronary angiography after resuscitated out-of-hospital cardiac arrest without ST-elevation on the electrocardiogram — Key result: Immediate coronary angiography did not improve 30-day survival versus a deferred strategy in unconscious out-of-hospital cardiac arrest without ST-elevation (54.6% vs 53.6%; HR 0.95, 95% CI 0.74-1.21; p=0.67).
- [CAG after OHCA](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64844): Coronary angiography after out-of-hospital cardiac arrest without ST-elevation — Key result: An individual-patient-data meta-analysis of five randomised trials (2,173 patients), including DISCO, found no difference in 30-day survival between immediate and deferred coronary angiography after out-of-hospital cardiac arrest without ST-elevation.
- [HeartRunner](https://synapsesocial.com/papers/6a94eafebf74ba694a821073): Out-of-hospital cardiac arrest survival following community first responder activation — Key result: Activation of community first responders did not improve 30-day survival after out-of-hospital cardiac arrest: 15% vs 17% (p=0.42) when estimated responder arrival was under three minutes, and 13% vs 14% (p=0.43) at three to nine minutes. Bystander CPR and defibrillation increased significantly, with no safety concerns.
- [Prague 26](https://synapsesocial.com/papers/6a8fbb6717152b56e6b64846): Catheter-directed thrombolysis in intermediate-high-risk pulmonary embolism — Key result: Catheter-directed thrombolysis reduced 7-day all-cause death, PE recurrence, or cardiorespiratory decompensation versus anticoagulation alone in intermediate-high-risk pulmonary embolism (0.7% vs 6.8%; RR 0.10, 95% CI 0.02-0.44; p<0.001). 7-day bleeding was 4.6% vs 5.0% (p=0.846).
- [LAACS-2](https://synapsesocial.com/papers/6a8fbb6817152b56e6b64847): Left atrial appendage closure concomitant with cardiac surgery — Key result: Concomitant left atrial appendage closure during planned open-heart surgery did not significantly reduce stroke or TIA versus standard care over a median 4.0 years (4.28% vs 5.04%; HR 0.85, 95% CI 0.53-1.37; p=0.517). Patients with CHA2DS2-VASc above the median had a 56% reduction (p=0.018).
- [REVEAL](https://synapsesocial.com/papers/6a944ee3e0b319fc0f780bc9): 124I-Evuzamitide PET/CT for diagnosing cardiac amyloidosis — Key result: In the REVEAL trial, 124I-evuzamitide PET/CT demonstrated a sensitivity of 94% (95% CI, 85%-98%; p<.001) and specificity of 86% (95% CI, 77%-92%; p<.001) for diagnosing cardiac amyloidosis.
- [ALL-RISE](https://synapsesocial.com/papers/69ccb55116edfba7beb8740c): CathWorks FFRangio vs Invasive Pressure Wire-Based Physiology Assessment for Coronary Revascularization Guidance — Key result: FFRangio (AI-based angiography-derived FFR) was noninferior to invasive pressure wire for guiding PCI: 1-year MACE 6.9% vs 7.1% (HR 0.98, noninferiority p=0.0008). First FDA-approved angiography-derived physiology trial in the US.
- [PRO-TAVI](https://synapsesocial.com/acc/trials/pro-tavi): Deferral of Routine PCI in Patients Undergoing Transcatheter Aortic Valve Implantation — Key result: Deferring PCI until after TAVI was noninferior to PCI-first (24% vs 26% composite endpoint, HR 0.89) with significantly less major bleeding (6% vs 15%). Only 11% of deferred patients needed subsequent PCI.
- [SMART-DECISION](https://synapsesocial.com/papers/69ccb7c216edfba7beb89e15): Discontinuation of Beta-Blocker Therapy in Stabilized Patients After Acute Myocardial Infarction — Key result: Discontinuing beta-blockers in stable post-MI patients without HF or LV dysfunction was noninferior to continuing treatment — first RCT evidence supporting beta-blocker de-escalation in this population.
- [DKCRUSH-VIII](https://synapsesocial.com/papers/69efc6fb5ce2fbd289d537f0): IVUS-Guided vs Angiography-Guided Double Kissing Crush Stenting for Complex Coronary Bifurcation Lesions — Key result: IVUS guidance for DK crush stenting in complex bifurcation lesions — results from 556-patient multicenter Chinese trial presented at ACC.26 and published in JACC.
- [HI-PEITHO](https://synapsesocial.com/papers/69ccb55116edfba7beb8740f): Ultrasound-Facilitated, Catheter-Directed Fibrinolysis for Acute Pulmonary Embolism — Key result: Ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduced the composite of PE-related death, cardiopulmonary decompensation, or symptomatic recurrence by 61% vs anticoagulation alone (4.0% vs 10.3%; RR 0.39, 95% CI 0.20-0.77, P=0.005) with no increase in major bleeding.
- [CHAMPION-AF](https://synapsesocial.com/papers/69ccb55116edfba7beb8740e): Left Atrial Appendage Closure vs NOACs as First-Line Therapy for Stroke Risk Reduction in Atrial Fibrillation — Key result: WATCHMAN FLX LAAC was non-inferior to NOACs for stroke prevention (5.7% vs 4.8% composite CV death/stroke/embolism at 3 years) and statistically superior for safety, with 43% less non-procedural major bleeding (10.9% vs 19.0%). Net clinical benefit favored the device (15.1% vs 21.8%).
- [STEMI-DTU](https://synapsesocial.com/papers/69e96f67f4ab80ef3c027464): Left Ventricular Unloading Before Reperfusion in Anterior STEMI Without Cardiogenic Shock — Key result: LV unloading with Impella CP for 30 min before PCI did NOT reduce infarct size vs immediate PCI (30.8% vs 31.9%, NS) in anterior STEMI without shock. Device-related bleeding/vascular complications were significantly higher (34% vs 6%).
- [VESALIUS-CV](https://synapsesocial.com/acc/trials/vesalius-cv): Evolocumab vs Placebo in Patients With Atherosclerosis or Diabetes Without Prior MI or Stroke — Key result: Evolocumab reduced 3-point MACE by 25% vs placebo in patients with ASCVD or diabetes but no prior MI/stroke (first demonstration of PCSK9 inhibitor benefit in primary prevention). Heart attack risk reduced 36%. LDL-C reduced 55% to median 45 mg/dL.
- [Intensive LDL-C Targeting in ASCVD](https://synapsesocial.com/papers/69ccb55116edfba7beb87410): Intensive vs Conventional LDL-C Targeting in Patients With Atherosclerotic Cardiovascular Disease (Ez-PAVE) — Key result: Targeting LDL-C <55 mg/dL vs <70 mg/dL reduced major CV events by 33% at 3 years (6.6% vs 9.7%) in ASCVD patients. CV death/MI/stroke was also significantly lower (2.3% vs 3.6%). First randomized head-to-head comparison of LDL-C targets.
- [GoFreshRx](https://synapsesocial.com/acc/trials/gofreshrx): Home-Delivered DASH Groceries and Effects on Blood Pressure and LDL-C in Black Adults With Hypertension — Key result: Home-delivered DASH groceries reduced systolic BP by 3.4 mm Hg more than grocery stipends (5.7 vs 2.3 mm Hg reduction) and LDL-C by 6.2 mg/dL more (8.0 vs 1.8 mg/dL) in Black adults in food deserts. Benefits did not persist after intervention ended.
- [Kardinal](https://synapsesocial.com/papers/6a025cddedf6f48138594a8c): Phase 2 Study of Tonlamarsen, an Antisense Oligonucleotide Targeting Angiotensinogen, in Uncontrolled Hypertension — Key result: Tonlamarsen achieved 67% reduction in plasma angiotensinogen (p<0.0001) but did NOT reduce office systolic BP more than single dose at Week 20 (both ~6.7 mmHg, p=0.97). Intriguingly, BP effects persisted after dosing stopped. Phase 2b trial in acute severe hypertension planned.
- [FAST III](https://synapsesocial.com/papers/69ccb55116edfba7beb8740a): Angiography-Based vFFR vs Invasive Pressure Wire-Based FFR for Guiding Coronary Revascularization — Key result: Angiography-based vFFR was noninferior to pressure wire-based FFR for guiding coronary revascularization: identical 1-year MACE rates with shorter procedures, less radiation, and less contrast.
- [ORBITA-CTO](https://synapsesocial.com/papers/69efc6f75ce2fbd289d537ee): Percutaneous Coronary Intervention for Chronic Total Occlusion: A Randomized Placebo-Controlled Trial — Key result: CTO PCI significantly reduced angina symptoms vs sham procedure in the first placebo-controlled CTO trial: 31 more angina-free days over 168 days, with improved quality of life scores. No deaths, MIs, or withdrawals.
- [CHIP-BCIS3](https://synapsesocial.com/papers/69ccb55116edfba7beb87411): Percutaneous Left Ventricular Unloading During High-Risk Coronary Intervention in Patients With Severe LV Dysfunction — Key result: LV unloading with Impella CP during complex PCI did NOT reduce adverse events in severe LV dysfunction (win ratio 0.85, p=0.30) and was associated with HIGHER all-cause mortality (32.6% vs 23.4%, HR 1.54) and CV death (26.7% vs 14.5%).
- [SCOUT-HCM](https://synapsesocial.com/papers/69ccb59f16edfba7beb8767e): Mavacamten in Symptomatic Adolescents With Obstructive Hypertrophic Cardiomyopathy — Key result: Mavacamten reduced LVOT gradient by 48.0 mmHg more than placebo (p<0.0001) in adolescent oHCM — first positive Phase 3 trial extending mavacamten to patients ages 12-17. Consistent efficacy across all secondary endpoints with favorable safety.
- [Lung Impedance-Guided HFpEF Therapy](https://synapsesocial.com/acc/trials/lung-impedance-guided-hfpef-therapy): Non-Invasive Lung Impedance-Guided Preemptive Treatment in Heart Failure With Preserved Ejection Fraction — Key result: Lung impedance-guided therapy reduced HF hospitalizations by 74% and HF mortality by 74% in HFpEF over 3+ years. Clinicians adjusted medications 2x more frequently with earlier intervention at the preclinical stage.
- [CADENCE](https://synapsesocial.com/papers/69cb6526e6a8c024954b9309): Sotatercept in Combined Post- and Precapillary Pulmonary Hypertension With Heart Failure and Preserved Ejection Fraction — Key result: Sotatercept significantly reduced pulmonary vascular resistance in HFpEF with CpcPH (0.3 mg/kg: -0.67 Wood units, p=0.004; 0.7 mg/kg: -0.33, p=0.024 vs +0.26 placebo). Time to clinical worsening reduced 82%.
- [Spironolactone in Heart Failure](https://synapsesocial.com/acc/trials/spironolactone-in-heart-failure): Spironolactone in Heart Failure With Preserved or Mildly Reduced Ejection Fraction (SPIRIT-HF) — Key result: Spironolactone did NOT significantly reduce HF hospitalizations or CV death in HFpEF/HFmrEF (12.7 vs 10.8 events per 100 patient-years). Unexpected increase in total hospitalizations, hypotension, and renal dysfunction in the spironolactone group.
- [TRI-FR (2-Year)](https://synapsesocial.com/acc/trials/tri-fr-2-year): Transcatheter Tricuspid Edge-to-Edge Repair vs Medical Therapy for Severe Tricuspid Regurgitation: 2-Year Outcomes — Key result: T-TEER for severe TR reduced the primary endpoint from 35% to 20% at 2 years, with 40% fewer HF hospitalizations (14% vs 23%). No crossover in the control group — first unconfounded long-term T-TEER outcomes.
- [PROTECT](https://synapsesocial.com/acc/trials/protect): Emboliner vs Sentinel Cerebral Embolic Protection Devices During TAVR (PROTECT H2H) — Key result: Emboliner was noninferior to Sentinel for 30-day MACCE during TAVR (4.9% vs 5.0%) with the lowest stroke rates in a trial of this size (2% vs 2.1%). Emboliner captured 3x more large debris particles.
- [SURVIV](https://synapsesocial.com/acc/trials/surviv): Transcatheter Mitral Valve-in-Valve vs Redo Mitral Valve Replacement for Failed Bioprosthetic Valves — Key result: Transcatheter mVIV reduced death/disabling stroke by 77% vs redo surgery at 1 year (5.3% vs 20.8%, HR 0.23, p=0.005). Zero CV deaths at 30 days with mVIV vs 12.5% with surgery. First randomized comparison of mVIV vs rMVR.
- [ESSENCE-TIMI 73b](https://synapsesocial.com/papers/69ccb72e16edfba7beb890b3): Effect of Olezarsen on Noncalcified Coronary Plaque Volume: The ESSENCE-TIMI 73b Coronary CTA Substudy — Key result: Despite dramatic triglyceride reduction (60-64%), olezarsen did NOT reduce noncalcified coronary plaque volume vs placebo at 12 months (p=0.36). Neutral imaging results despite robust lipid changes.
- [Digoxin in Rheumatic Heart Disease](https://synapsesocial.com/acc/trials/digoxin-in-rheumatic-heart-disease): Digoxin and Clinical Outcomes in Rheumatic Heart Disease (Dig-RHD) — Key result: Digoxin reduced the composite of death or new/worsening HF by 18% in rheumatic heart disease — first randomized trial of digoxin in RHD. Toxicity was rare (1%) with no related deaths.
- [OPTIMAL](https://synapsesocial.com/papers/69ccb55116edfba7beb87419): OPTIMAL Trial — ACC.26 Late-Breaking Clinical Trial — Key result: Late-breaking results from the OPTIMAL trial presented at ACC.26 — published in NEJM.
- [IVUS CHIP](https://synapsesocial.com/papers/69ccb55116edfba7beb87420): Intravascular Ultrasound-Guided vs Angiography-Guided PCI in Complex Coronary Lesions — Key result: IVUS-guided PCI in complex coronary lesions — results from a landmark European multicenter trial presented at ACC.26 and published in NEJM.
- [SirPAD](https://synapsesocial.com/papers/69ccb55116edfba7beb87414): Sirolimus-Coated Balloon vs Uncoated Balloon Angioplasty for Peripheral Arterial Disease — Key result: Results from the world's largest sirolimus-coated balloon trial in peripheral artery disease (N>1,250) were presented at ACC.26 and published in NEJM.
- [THRIVE Pilot](https://synapsesocial.com/acc/trials/thrive-pilot): THRIVE Pilot Trial — ACC.26 Late-Breaking Clinical Trial — Key result: Late-breaking results from the THRIVE Pilot trial presented at ACC.26.

## Data Sources

Synapse aggregates and enriches data from OpenAlex, PubMed/MEDLINE, Crossref,
ClinicalTrials.gov, ACC/AHA/ESC clinical practice guidelines, and FDA.

## Content Enrichment

All papers undergo AI-powered enrichment: clinical evidence extraction using
structured PICO framework, methodology classification with level-of-evidence
scoring, claims extraction, contradiction detection, research context
analysis (novelty, consensus alignment), and guideline recommendation linking.