Adenozine Issue 2
Cardiac Emergency Evidence, without the fluff
EDITOR’S NOTE
Welcome to Issue 2 of Adenozine!
I feel honoured to see so many people subscribe and read the first edition- thank you and please feel free to recommend the newsletter to colleagues far and wide :)
This newsletter exists because keeping up with cardiac emergency evidence while working in a busy ED is genuinely hard. My aim is simple: cut through the noise and deliver what matters for frontline practice, in the time it takes to finish a coffee.
We’ve got two papers this issue. One RCT that gives you a real reason to reach for a second defibrillator. It’s not straight off the press but it’s not in the ANZCOR yet- maybe something we should be thinking about? Definitely food for thought…
The other paper is a state-of-the-art review that finally asks what happens to cardiogenic shock patients after you save them — and the answer is sobering. Let’s go!
If there’s a topic or paper you’d like covered in a future issue, hit reply. I’d genuinely love to hear from you.
Joe Rotella
Emergency Physician, Clinical Toxicologist, and Cardiac Emergency Research Lead (Victorian Heart Hospital, Monash Health)
Paper 1: Two defibrillators. One case of refractory VF. Double the survival.
The DOSE VF Trial
Cheskes S, Verbeek PR, Drennan IR, et al. Defibrillation Strategies for Refractory Ventricular Fibrillation. N Engl J Med. 2022;387(21):1947-1956. doi:10.1056/NEJMoa2207304
Please note, this was a study published in NEJM by Emergency Medicine Physicians- worthy of much respect!
The setup: Cluster-randomised controlled trial with crossover across six paramedic services in Ontario, Canada. 405 patients with refractory ventricular fibrillation during out-of-hospital cardiac arrest, defined as VF persisting after three consecutive standard shocks with 2-minute CPR intervals in between.
Three arms: standard defibrillation (pads stay anterior-lateral), vector-change defibrillation (VC; pads switched to anterior-posterior after the third shock), or double sequential external defibrillation (DSED; a second set of pads added in the anterior-posterior position, with a second defibrillator delivering a near-simultaneous second shock). Primary outcome: survival to hospital discharge.
What happened: The results are striking. Survival to hospital discharge was 30.4% in the DSED group vs 13.3% in standard — a relative risk of 2.21 (95% CI 1.33–3.67). VC defibrillation also beat standard: 21.7% vs 13.3% (RR 1.71; 95% CI 1.01–2.88).
Good neurological outcome (modified Rankin Scale ≤2) also significantly higher with DSED (27.4% vs 11.2%; RR 2.21, 95% CI 1.26–3.88) with VC trending in the same direction but not reaching significance. All three groups received similar doses of epinephrine and antiarrhythmics, making a drug-effect confound unlikely.
A few things to sit with:
The trial was stopped early by the data safety monitoring board due to COVID-related operational disruptions — it enrolled 405 of a target 930. The planned sample size wasn’t met. The fragility index for DSED is 9 (reassuring), but for VC it’s just 1- meaning a single outcome change would flip significance. Take the VC result with appropriate caution.
Fragility index = the minimum number of patients whose status would have to change from a nonevent to an event that is required to turn a statistically significant result to a non-significant result. The smaller the number, the more ‘fragile’ the significance of the trial’s findings- there’s a nice run down on Life in the Fast Lane
The mechanistic rationale makes sense. Standard anterior-lateral pads create the weakest voltage gradient in the posterior left ventricle, which is exactly where fibrillation tends to persist or restart after failed shocks. VC fixes the vector; DSED also adds energy from the second shock. Both plausible mechanisms, slightly different contributions. The evidence suggests that its about the vector not the current that makes the difference…
Nearly 90% of patients received their randomly assigned defibrillation strategy throughout the trial. CPR quality was high and consistent. These aren’t the methodological sieve of most prehospital trials. Practical- good for us!
The main practical limitation for DSED: you need a second defibrillator on scene. In urban services that’s usually achievable with two paramedic units; in regional settings it’s a real constraint. VC requires only one machine.
The majority of patients were from urban settings, which limits direct extrapolation to remote practice.
The bottom line: DSED delivers a near-doubling of survival in refractory VF - a condition that’s otherwise a near-certain death sentence. VC is a reasonable single-defibrillator alternative.
I’m keen to hear from Australian colleagues if anyone is used DSED in refractory/recurrent VF- drop me a line, I’d love to hear about it!
🟢 Quality Flag: Green.
Cluster-RCT with crossover design, strong CPR quality control, patient-centred outcomes, and consistent sensitivity analyses. Stopped early and underpowered for some secondary endpoints and the VC result in particular needs replication but DSED’s signal is hard to dismiss.
Paper 2. Cardiogenic shock: we got better at saving them. Now we need to figure out what we’re saving them for.
Samuels A, Zolotarova T, Eisenberg MJ. Cardiogenic Shock: A State-of-the-Art Review. Am J Cardiol. 2026;266:42-51. doi:10.1016/j.amjcard.2026.02.024
The setup: State-of-the-art narrative review from McGill/Jewish General, covering classification frameworks, therapeutic strategies, and critically, the emerging survivorship literature in cardiogenic shock (CS). Covers evidence through October 2025. Definitely up to date…
The classification landscape: Two frameworks now coexist. The SCAI staging system (A through E: at-risk → extremis) is your haemodynamic severity tool, which is useful for tracking progression and escalating support. The newer SHARC framework classifies by etiology: AMI-related CS, HF-related CS (de novo and acute-on-chronic), post-cardiotomy CS, and secondary CS. The etiology shift matters clinically: in a 2024 multinational registry using SHARC definitions, 59% of CS was attributable to heart failure and only 27% to AMI.
HF-CS has overtaken AMI-CS as the dominant phenotype and it carries worse post-discharge mortality (19.3% vs 8.5% at one year).
What actually works — and what doesn’t
Vasopressors and inotropes: The SOAP II trial established norepinephrine over dopamine in the CS subgroup (dopamine was associated with significantly higher 28-day mortality and more tachyarrhythmias). The DOREMI trial found milrinone and dobutamine equivalent on a composite outcome including death, cardiac arrest, and transplant. Neither class has demonstrated mortality benefit in isolation. They buy time not outcomes.
Revascularisation in AMI-CS: The SHOCK trial showed no 30-day mortality benefit, but a clear benefit at 6 months (50.3% vs 63.1% mortality) and 1 year. This remains the cornerstone of AMI-CS management. The CULPRIT-SHOCK trial refined strategy: culprit-vessel-only PCI reduced the composite of 30-day mortality or renal replacement therapy compared to immediate multivessel PCI. Resist the urge to fix everything.
IABP: Widely used, mostly not useful. The IABP-SHOCK II 6-year follow-up found no mortality difference, and no difference in QoL, NYHA class, or functional status between groups. In HF-CS, the group we are most worried about, a 2025 meta-analysis found no survival benefit though a subgroup analysis in SCAI stage C or D patients may suggest some benefit. The 2025 AHA guidelines now recommend against routine IABP in AMI-CS.
Impella: No significant reduction in 30-day mortality in AMI-CS, but a signal at 6 months (OR 0.64; 95% CI 0.43–0.95). Higher complication burden with bleeding, limb ischemia, and hemolysis. Higher-flow devices (5.5 vs 5.0) appear to have better outcomes. Earlier implantation (before PCI) associated with improved short- and mid-term survival. The 2025 AHA guidelines support selective use in severe or refractory AMI-CS. Not that common in Australia but there is uptake centres including in mine- watch this space
VA-ECMO: No mortality benefit in four randomised trials in AMI-CS. Higher rates of bleeding and limb ischemia. Resource-intensive. Left ventricular afterload rises with isolated VA-ECMO due to retrograde aortic flow - LV distension worsens ischaemia. Left ventricular unloading (ECpella- combining VA-ECMO with Impella) is now showing a mortality benefit in meta-analysis (n=9,858), with effect concentrated in patients unloaded within 2 hours of ECMO initiation.
The survivorship gap — the part most reviews skip:
This is where the review earns its place. Acute mortality has improved. What happens next is less encouraging. In a 2023 cohort of nearly 10,000 CS patients: 42% required a higher level of care than before admission, 47.5% were readmitted within a year, and 15.3% died in the first year post-discharge. Among AMI-CS survivors, the incidence of new mental health diagnoses was 109.6 per 1,000 person-years. Female patients fare worse across in-hospital outcomes and at 1- and 3-year follow-up. HF-CS patients have 31-day to 2-year mortality roughly double that of AMI-CS patients (45% vs 22%).
Knowing what happens next is useful to us as it gives us some additional information when speaking to families when it comes to next steps- it’s definitely not over, Red Rover, but there’s a journey ahead. Time will tell
The bottom line: The therapeutic landscape for CS keeps evolving, but most interventions improve short-term hemodynamics without clear long-term mortality or QoL benefit. The real emerging story is survivorship - a growing population of CS survivors discharged into a healthcare system with almost no structured follow-up. The clinical and research priority is shifting from “keeping them alive in the ICU” to “what kind of life are they going home to.”
🟢 Quality Flag: Green (reference-grade review). Not primary data, but one of the cleaner CS reviews published in recent years. Well-structured, honestly appraised, and genuinely useful as a single-reference summary of the field. The survivorship section is particularly valuable - it’s the part of CS care that’s least discussed and most overdue for attention.
Adenozine is written for emergency physicians and cardiologists with an interest in cardiac emergency evidence. Nothing here constitutes clinical advice — use your brain, consult your local guidelines, and talk to a cardiologist when the situation requires it.
Next issue: TBA — send paper suggestions to the inbox.