Sakthivel

Consultant Cardiologist and Electrophysiologist, Dr KMH

[John Mandrola, MD @drjohnm]

Mandrola-ism: by a million miles, the best tool to sort syncope is to turn off your phone, pull up a chair at the bedside and listen to the story. The whole story. Every detail.

[Sakthivel @drsakthivelep]

@willsuh76 @drjohnm @DrRoderickTung Clearly dyssynchronous

[Elad Anter @EladAnter]

🔥 Hot off the press: We identified how and where AF begins.

I am excited to share this work.

Since the discovery of PV triggers more than 25 years ago, AF ablation has evolved into an empiric therapy centered on PVI. Yet, we have never been able to identify the arrhythmogenic substrate that determines why a premature beat initiates AF at one site and not another.

We believe this study changes that.

In this mechanistic study, we found that AF initiation arose predominantly through reentry originating from a small number of spatially discrete regions with steep repolarization gradients. Their distribution was unique to each patient, and they accounted for more than 92% of AF initiation episodes.

Importantly, the arrhythmogenic substrate was not defined by low voltage, and while conduction abnormalities were often present, they appeared to play a secondary role.

Its patient-specific distribution may help explain the controversy surrounding posterior wall isolation: the posterior wall harbored the substrate in only approximately 30% of patients. Importantly, in redo patients with durable PVI, right-atrial substrate (which is often beyond standard mapping strategies) was identified in 30%.

Most encouragingly, in an exploratory cohort of 24 patients with recurrent AF and durable PVI (50% PerAF), targeted elimination of these sites achieved 87.5% single-procedure freedom from any atrial tachyarrhythmia over a median of 489 days, without antiarrhythmic drugs.

The thoughtful accompanying editorial by Jon Kalman highlights the significance of this discovery and its central translational challenge of bringing it into real-world clinical practice.

But stay tuned! Technology is under development to transform this discovery into a rapid, automated functional mapping.

Current electroanatomic mapping relies largely on voltage amplitude and activation timing. We need to move beyond these measures and map how tissue actually functions - how it conducts, repolarizes, and responds to premature stimulation. This can add the critical dimension that has long been missing from substrate mapping and may reveal what truly makes cardiac tissue arrhythmogenic.

To me, this is the beauty of physiology: there are no black boxes. We can identify the sites that reproducibly initiate the arrhythmia, define their EP properties, eliminate them with ablation, and confirm that arrhythmia can no longer be initiated.

The next steps are prospective multicenter validation and technological development. Together, they may move AF ablation beyond empiric therapy toward truly individualized, mechanism-guided therapy.

📄 Paper in @JACCJournals:
https://t.co/izIR8HbNYk
📝 Editorial:
https://t.co/mYIilXkjJ7

#JACCCEP #AtrialFibrillation #CardiacElectrophysiology #CatheterAblation #EPeeps

[TheLiverDoc™ @theliverdoc]

Requesting the Government of India - honorable President @rashtrapatibhvn, @PMOIndia to withdraw the fourth highest civilian award bestowed on this quack - to maintain credibility and sanctity of such awards. This is shameful and atrocious. This woman's social media accounts are now being witheld because of legal demands in India due to cognizance of the public health danger she promotes.

In her Padma Award citation, the red-lined sections mentions "claims of" cure of serious illnesses and chronic diseases - this is an outright violation of Drugs and Magic Remedies Act. This woman should be chargesheeted and these "wild" claims investigated. Show some respect to the public you serve @PadmaAwards

Indian public in general maybe 'blind' health illiterates, but not all are! @arunachaltimes_

[Sakthivel @drsakthivelep]

@PurumittalDr Quinidine Verapamil Ablation

[Sakthivel @drsakthivelep]

@DrRajeshG1 Trial CV/SR maintenance. If not, AVJ ablation and pace.
Dialyse well & Meds.
Still persistent MR and TR: Repair
Needs TEE and CMR.

[Sakthivel @drsakthivelep]

@drameya @indian_rhythm @HRSonline First is Epicardial, Summit region, AIV
second PVC likely from mid posterior rvot/RCC

[Sakthivel @drsakthivelep]

@sumitvermaep @DavidLBrownMD @drjohnm @KostekMilan Just asking. What ischemia evaluation will you do in a high CAD risk patient with AF prior to starting flecainide (or not needed at all)?

[Elad Anter @EladAnter]

There’s something uncomfortable about watching our field race forward with blinders on. Not out of ignorance, but because the path is familiar, the tools keep improving, and every new tech is met with celebration.

Stopping to question our direction has become harder than building the next catheter.

New tools are helpful, but they have not moved the needle enough to meaningfully change outcomes, and something important, I feel, is being missed.

I’ve had my share helping to build some of these technologies, and I believe in this work. But that’s exactly why I feel the responsibility to say this.

Take posterior wall isolation. It doesn’t help everyone. Trials keep coming back neutral, and they will continue to, until we understand which patients actually benefit and why.

We’ve spent decades refining how we record and read voltage and activation data, adding electrodes, improving algorithms. Indeed, the maps look better, but the outcomes, not so much.

PFA is a great advancement, easier to use, procedurally efficient, creates more consistent lesions. That matters, but it will not change the trajectory of clinical outcomes.

At some point, that pattern stops being a coincidence. It becomes a signal that we may not be solving the right problem. The real gap, I suspect, isn’t in our catheters or our maps. It’s in our understanding of the disease itself.

Why does an APC trigger AF in one patient and not another, or from one location and not from another? What is the true arrhythmogenic substrate- is it really scar? Is AF really a left atrial disease? We know it is not, so how do we identify who has right atrial disease, and how do we map and target it?

We don’t fully have those answers, and no new tool will give them to us.

Closing the mechanism gap, that’s the work we need to do. Everything else, is refinement within a paradigm that may have already reached its ceiling.

The blinders come off when we’re willing to slow down and ask whether we’re racing in the right direction.

I’m fortunate to have worked with an incredible team over the past many years, that has taken on some of these questions directly. We’ll be presenting our findings on April 25 at 9:30AM at the High Impact Science session, and I hope it’s the beginning of a longer conversation.

@HRSonline @BarkaganMichael @MilmanAnat @drjohnm

[Praggnanandhaa @rpraggnachess]

We had the honour of meeting Manuel Aaron Sir, Pioneer of Indian chess. At 92 his passion is still unmatched and analyzing all top-level games. Truly inspiring and lot of respect🙏🙏

[Sakthivel @drsakthivelep]

@SrihariNaiduMD @HcmPatient @hcmsociety @noshreza @tikuowens @MasriAhmadMD @purviparwani @DavidWienerMD @adityadoc1 @GiorgioMedranda @EllauziRama What's your experience with CMI in midcavity obstruction? Can we use them liberally?

[Sakthivel @drsakthivelep]

@Jasonphilip8 Treat LDL harder with triple drug hit plus mounjaro or sema for best CV protection
You will be hale and hearty, best wishes sir.

[Stefano Garzon @stefano_garzon]

Koeckerling et al. just dropped in @JACCJournals: a reconstructed-IPD meta-analysis of all 5 RCTs comparing PCI vs CABG for left main disease (LE MANS, SYNTAX, PRECOMBAT, EXCEL, NOBLE). 4,499 patients pooled. The headline: 10-year all-cause mortality is virtually identical — 23.4% vs 23.3%, HR 1.02 (0.89–1.17), RMST difference of exactly 0.0 years.

This is genuinely good news. For patients with left main disease and low-to-intermediate anatomic complexity who are eligible for both strategies, we can now tell them with reasonable confidence: your chances of being alive at 10 years are the same regardless of which path you choose.

The methodology deserves praise. The team used reconstructed time-to-event IPD (via the IPDfromKM algorithm) with 98.7% fidelity, pooled in a 1-stage Cox model with γ-frailty for trial, verified proportional hazards (Schoenfeld P=0.59), ran RMST as a complementary analysis, and confirmed everything with conventional fixed/random effects meta-analysis. Every approach converges to the same number. That's reassuring.

But as with any meta-analysis, the fine print matters. A few observations:

𝗧𝗵𝗲 𝗘𝗫𝗖𝗘𝗟 𝗾𝘂𝗲𝘀𝘁𝗶𝗼𝗻

EXCEL is the largest trial (n=1905, 23% of the weight) and the only one with contemporary 2nd-gen DES (everolimus). It's also the only trial censored at 5 years — no 10-year follow-up, none planned. And it was the only trial showing a statistically significant excess in all-cause mortality with PCI at 5 years (13.0% vs 9.9%, difference 3.1 pp).

@GreggWStone et al. themselves wrote in NEJM 2019: "at this time point the hazard curves were continuing to diverge. Ten-year follow-up is needed."

Administrative censoring at 5 years is statistically valid — it doesn't bias the HR within the observed window. But it removes the possibility of detecting whether the divergence continued or reversed. The other 4 trials that DO have 10-year data all used 1st-gen DES or BMS. So the question "what happens to everolimus-eluting stents in left main at 10 years?" remains genuinely unanswered.

𝗥𝗲𝗰𝗼𝗻𝘀𝘁𝗿𝘂𝗰𝘁𝗲𝗱 𝗜𝗣𝗗 ≠ 𝘁𝗿𝘂𝗲 𝗜𝗣𝗗

The reconstruction method is validated and reliable for time-to-event data. But it cannot recover individual covariates. This means the meta-analysis cannot test treatment-by-subgroup interactions for diabetes, acute coronary syndromes, or SYNTAX score at 10 years. The Sabatine et al. IPD meta-analysis (Lancet 2021) found no interaction at 5 years — but extrapolating that to 10 years is an assumption, not a finding.

This matters because the NOBLE 10-year paper (Holck et al., Lancet 2026) found a significant interaction between ACS presentation and mortality (HR 0.57 favoring PCI in ACS, p_interaction=0.049). If confirmed, this would have major practical implications. But it couldn't be tested in the pooled analysis.

𝗠𝗼𝗿𝘁𝗮𝗹𝗶𝘁𝘆 𝗲𝗾𝘂𝗮𝗹 ≠ 𝗼𝘂𝘁𝗰𝗼𝗺𝗲𝘀 𝗲𝗾𝘂𝗮𝗹

The meta-analysis only reports mortality. No MI, no stroke, no repeat revascularization. This is a deliberate and defensible choice (mortality is the hardest endpoint, immune to ascertainment bias). But it leaves the conversation incomplete.

As an exercise, I pooled the 3 trials that report non-mortality endpoints at their longest available follow-up (LE MANS 10yr, PRECOMBAT 10yr, EXCEL 5yr — ~2,610 patients). Exploratory, not definitive, but informative:

→ Repeat revascularization: RR 1.66 (1.36–2.03). Significantly and consistently higher with PCI. No surprise — but the magnitude matters for shared decision-making.

→ Total MI: RR 1.12 (0.87–1.46). Apparently neutral. But EXCEL shows why this is misleading: periprocedural MI favored PCI (RR ~0.66) while spontaneous MI favored CABG (RR ~1.92). They cancel out in the composite. Classic Simpson's-adjacent phenomenon — the total hides a divergence that matters clinically.

→ Spontaneous MI (EXCEL-driven): RR 1.64 (1.14–2.38), P=0.008. This is the trade-off the patient needs to hear. CABG appears to protect better against late spontaneous infarction — plausibly because grafts bypass vulnerable proximal plaques that stents don't address.

Caveat: SYNTAX and NOBLE didn't collect these endpoints between 5–10 years, so this analysis is incomplete. It's a conversation starter, not a conclusion.

𝗛𝗼𝘄 𝗱𝗼𝗲𝘀 𝗢𝗣𝗧𝗜𝗠𝗔𝗟 𝗳𝗶𝘁 𝗶𝗻?

The OPTIMAL trial (Testa et al., NEJM 2026) just showed that IVUS-guided PCI adds no benefit over angiography-guided PCI in left main (HR 1.11, 0.87–1.42). This seems to contradict the NOBLE IVUS substudy (20% vs 31% mortality with/without final IVUS).

But there's no contradiction. The NOBLE observation was confounded by indication. OPTIMAL randomized the comparison and found that in expert hands — operators who already internalize IVUS-derived optimization criteria — the imaging itself doesn't add incremental value. The control arm had 96% post-dilation rates and 85% POT. That's not "angiography-naïve" PCI — it's PCI done by people who think with IVUS even when they don't use it.

This actually reinforces the Koeckerling findings: PCI in the included trials, even without mandated imaging, achieved equivalent mortality to CABG. If even IVUS doesn't move the needle in expert centers, then the mortality equivalence reported in the meta-analysis is likely robust and not contingent on a hypothetical "better PCI."

𝗧𝗮𝗸𝗲-𝗮𝘄𝗮𝘆

My thoughts:

1. PCI and CABG offer the same probability of being alive at 10 years in patients with left main disease and SYNTAX ≤32. This is established.

2. But equal survival is not the same as equal outcomes. PCI means ~66% more repeat revascularization and likely more spontaneous MI. CABG means more periprocedural stroke and a harder early recovery.

3. The choice isn't about which is "better." It's about which set of trade-offs aligns with the patient sitting in front of you — their anatomy, their comorbidities, their values, their fear of surgery vs. their tolerance for reintervention.

Equal mortality is the foundation. The rest is shared decision-making. Again, kudos to the authors. This is beautiful work!

#CardiologyX #InterventionalCardiology #LeftMain

[Amitabh Yaduvanshi MD, DM, FACC, FSCAI @IntervnCardio]

1/10
🚨 In 1989, a clinical trial STOPPED EARLY because patients were dying.

The drug? Flecainide—a Class Ic antiarrhythmic.

The result? Doctors abandoned it for heart patients.

But 35 years later, NEW research from 1.5M patients is reopening the debate.

Here's the controversy 🧵👇

[Sakthivel @drsakthivelep]

@drjohnm @Sensible__Med The sky is blue and every V trial is also positive. V for vericiguat tested in WHF and SHF. Waiting to listen to your POV. Reliable 5th pillar?

[Sakthivel @drsakthivelep]

@IsaParam Change in VA activation from left posterior (close to median) to left anterior pathway (distant free wall) following slight wobble in CL; prematurity results in VA refractoriness in the former.

[Sakthivel @drsakthivelep]

@karthik2k2 Hi Sir. You could have mentioned the cardiologist's name just like you have mentioned prof bala sir's name. Remembering how prof.JBC maintained his pacemaker patients' complete record during his entire active career, written by himself as if like calligraphy and preserved well.

[Sakthivel @drsakthivelep]

@FCademartiri @iamritu The hypothesis is consistent with tirzepatide benefits in summit; similarly it's renoprotective effects as well.

[Sakthivel @drsakthivelep]

@UlhasDr Paraseptal AT.

Right inferior force;Any CHD?

[Sakthivel @drsakthivelep]

@DrRajeshG1 Two ascents (or one staggered ascent) with one descent. Patient could be in sinus rhythm.