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Archive for May, 2024

How many molecules of LDL penetrate the coronary arterial endothelium per day?

Posted in Uncategorized on May 26, 2024|

“Half-baked knowledge is not better than fully-baked Ignorance“

LDL is portrayed as villain de-chief of Atheroscerlois and CAD. But, LDL with a 100 to 160 mg concentration, is in constant circulation, in a smooth manner serving other physiological vascular functions.

The forcible evidence that LDL can pierce an Intact endothelium is so huge no one can have the courage to dispute it. But, it doesn’t happen in the majority is the mysterious truth.

Electron microscopic picture of 20nm sized LDL molecules in circulation. They are not as frightening molecules as they are portrayed

What factors induce LDL to enter the endothelial gap junctions.?

Some facts

The diameter of LDL particles is about 20–30 nm which is much larger than that of gap-junctions (3–6 nm) between adjacent cells in continuous endothelium (Iuliano, Micheletta, & Violi, 2001). Hence, the only way for LDLs to cross the endothelium is through a process called caveolae-mediated transcytosis.

Contrary to the shout-out, LDL is not a true villain in all patients with CAD. It is something else, we aren’t aware of that keeps the LDL either passive or promotes its penetration.

There are at least five important factors.

1. Baseline Endothelial Integrity & vascular aging

2. Accelerated caveolae formation,

3,The shear stress of flowing BP .

4 .The associated diabetic basement membrane dysfunction.

5. Finally, the aggressiveness of native LDL molecule (Absolute levels of LDL are less important than we think . Please note, the much-researched South Asian metabolic syndrome has near normal LDL )

What we fail to acknowledge is the fact that our understanding of endothelial lipid interaction is based on poor-quality data . Meanwhile, the concept of endothelial-friendly LDL can’t be eliminated totally.

Final message

How many molecules of LDL enter endothelial breakpoints?

I am sure, no one can answer this question. In fact, this question need not be answered. Still, the PCSK blockers, the Inclisirons are the new armed weapons in anti LDL industry waiting hungrily to Invade the vasculature. What if these agents swallow good LDLs ?

Let us first clarify, the true invading potential of LDL before falling for these costly semi-annual subscription-based drugs. Meanwhile, HDL dysfunction with its Apo A2 interaction defects may be a more concerning issue than LDL-mediated injury is coming up.

Reference

1. Francesca Luchetti, Rita Crinelli, Maria Gemma Nasoni, Serena Benedetti, Francesco Palma, AlessaLDL receptors, caveolae and cholesterol in endothelial dysfunction: oxLDLs accomplices or victims ? British Journal of pharmacology.
https://doi.org/10.1111/bph.15272

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Coronary Leriche syndrome: An often missed sub-set of left main STEMI

Posted in Uncategorized on May 16, 2024|

Leriche syndrome (1948, Annals of Surgery, College de Paris, France) is a famous eponym in Aortic vascular emergency, where a saddle-shaped thrombus folds across the Aortic bi-furcation resulting in bilateral lower limb vascular insufficiency.

Though such vascular emergencies can occur in any bifurcation point in a vascular tree, it is not often thought about in acute coronary syndrome.

Large thrombus burden in LAD or LCX is so commonly visualized, while in a stump left main, we often fail to recognize the fact, that it is almost the same as “saddle embolus” sitting across both LAD & LCX bifurcation.

Most such patients do not reach the hospital. If the thrombus migrates to one of the branches, it might evolve either as LAD STEMI, LCX STEMI, or a combination of both. We have seen a few lucky Left main STEMIs in the cath lab, with some spontaneous canalization.

Final message

De-novo Coronary Leriche syndrome is a real entity. For many of us this may appear, just an acute coronary curiosity, since most of the time it results in silent sudden deaths and escapes from our vision. However, primary PCI Interventionalists need to be aware of this concept, as meddling in this critical arena with high thrombus load can rapidly evolve into an acquired Leriche syndrome, for which the operator becomes squarely responsible.

Reference

1.Leriche R, Morel A. The Syndrome of Thrombotic Obliteration of the Aortic Bifurcation. Ann Surg. 1948 Feb;127(2):193-206. doi: 10.1097/00000658-194802000-00001. PMID: 17859070; PMCID: PMC1513778.

Link 2

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What are the possible mechanisms of simultaneous Inferior and Anterior STEMI?

Posted in Uncategorized on May 16, 2024|

1. Wrap around LAD true Global MI

wrap-around-lad

 

2. RCA-dependent LAD circulation through collaterals

RCA dependent lad circulation

 

3. True bifurcation STEMI with static thrombus  (Carinal trapping of thrombus  ,Coronary Lerish sydrome )

4. Embolic  STEMI with showers of emboli  into both LCX and LAD

thrombus leriche syndrome equivalent in coronary

Simultaneous or sequential Anterior and Inferior STEMI

5. Mid or Proximal LAD lesion with proximal thrombus build-up

Further possibilities 

 Mimickers: Distal LAD lesions -Inferior ST elevation due to sparing of diagonal

 Wrong diagnosis -ERS pattern, pericarditis etc.

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When will the “Rate vs Rhythm” control debate in AF will end ?

Posted in Uncategorized on May 15, 2024|

We have more than solid evidence, that rate control is good enough or even better than rhythm control in the management of AF , for more than two decades. Studies that showed either equipoise or rate control was marginally superior in certain clinical parameters are.

1.AFFIRM (2002)

2.RACE

3.STAF(2003)

4.HOT-CAFE (2004)

Now, in 2020s with modalities like ablation, the choice is being pushed toward Pro-rhythm control. (Of course with evidence).Some of these studies are,

1.EAST-AFNET (2020)

2.CASTLE AF(2018)

3.RAFT AF (Again equivocal)

With emerging new technologies, scientists are trying whether more safer methods like cryoablation or pulse-filed ablation would beat the rate control with drugs. Still, rhythm control strategy is finding it tough to win over the apparently less scientific rate control strategy. (Why? The reason is discussed elsewhere )

“How can rhythm control be inferior or non-superior? Something is wrong. We can’t leave it like that. Let’s do a meta-analysis”

Even meta-analysis couldn’t help out rhythm control strategy.(Caldeira, Daniel et al. “Rate versus rhythm control in atrial fibrillation and clinical outcomes: updated systematic review and meta-analysis of randomized controlled trials.” Archives of cardiovascular diseases 105 4 (2012): 226-38 .)

Now, what shall we do? , Let us do another meta-analysis. A fresh one is released just a few days ago in 2024 . This mega meta-analysis with almost similar data, clearly vouchs for the superiority of early rhythm control with some form of ablation. It is gratifying that, with this study, we could sustain some confusion, in the management of this most common cardiac arrhythmia.

When will this fight for Rate vs Rhythm control in AF end?

Answer: It will not stop as long as an entity AF exists. Research, as the name implies, we need to search again, & again for truth. However, In the case of AF, I think, a different game is being played in the EP arena. It looks like, we are fighting with an established truth, not fighting for the truth.

Reference

1.Stefanos Zafeiropoulos, Ioannis Doundoulakis, Alexandra Bekiaridou et al Rhythm vs Rate Control Strategy for Atrial Fibrillation: A Meta-Analysis of Randomized Controlled Trials J Am Coll Cardiol EP. May 08, 2024. Epublished DOI: 10.1016/j.jacep.2024.03.006

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