C.May be , an Important link . (Will wait for evidence)
D.No link at all.
Answer:
There has been many postulations linking the two. 1.Cross over of vasoactive substances like serotonin . 2.Paradoxical microemboli that trigger a cortical migraine like aura .3.Transient hypoxemia due to right to left shunt during valsalva strain.
However ,the truth appears to be, it is more of an association , since both entities are very common in the general population.(Up to 20%) .If you ask for a pragmatic answer, it will be determined by the tempting desire to close an innocuous hole in the heart.
Postamble
While, the connection between migraine and PFO is speculative , but its link to cryptogenic stroke may be little more firm, although fear mongering is not warranted . (RoPE criteria: Risk of Paradoxical Embolism)
Answer: You should have guessed it right. If not, read the following, might help you out.
The first and foremost point is to understand the difference between LV dysfunction and failure. LV failure is a clinical diagnosis. LV dysfunction is an echocardiographic diagnosis.BNP can increase due to any mechanical stretch of LV and may rise even with Atrial stretch . Every patient with baseline LV dysfunction will show mild elevation. Sudden spikes can come with clinical worsening. However, to our surprise the NT pro BNP levels is not found to be correlating with severity dyspnea or orthopnea .
Most importantly NT Pro BNP can elevate in isolated subclinical diastolic dysfunction. This makes interpreting its level more complex.
*Additionally, BNP levels can be falsely elevated in renal failure and may be spuriously normal in obese individuals with left ventricular dysfunction. These disparities are due to variations in contributions from preformed (Granular cell depots) and freshly synthesised NT Pro BNP. The later process is severely impaired in obesity.
The following chart illustrates conditions that can cause elevated NT Pro-BNP levels beyond heart failure.
The answer to the question : Every response A to D is correct.
Final message
Relying too much on biochemistry, such as NT pro BNP to diagnose heart failure clouds our clinical judgment.Please realise ,NT pro BNP is not a creatinine equivalent for renal failure .Diagnosis of cardiac failure should focus on clinical criteria and symptoms, with NT pro BNP serving more as a prognostic rather than a diagnostic tool.(The good old Framingham criteria still stands strong & relevant )
TAVI has become a popular Aortic Intervention, but the risk of coronary obstruction (Left main & RCA too) is often underestimated , it can happen during the procedure or in the long term .High degree of anticipation is essential. The exact incidence is not known as reporting the event is far less than, what it is actually. Following are the suggested precautions to prevent coronary obstruction.
Pre-Procedural Assessment
Low Coronary Ostial Height: Identify if the Left Main origin is (< 10–12 mm )from the aortic annular plane, that will increase the chance of struts covering the ostia.
Shallow Sinuses of Valsalva : A shallow sinus( < 30 mm )leaves insufficient room for the displaced native leaflet, directing it toward the ostium.
Leaflet Length and Calcification: Evaluate for heavy calcification or a long native leaflet that exceeds the height of the coronary ostium, as these are easily pushed into the vessel opening.
Virtual Valve-to-Coronary (VTC) Distance: In Valve-in-Valve (ViV) procedures, calculate the VTC distance. A computed distance less than 4 mm indicates risk of coronary obstruction.
Risk factors for potential coronary obstruction.
Image source Ref 2
*Leaflet length is a very critical parameter, which was ignored in the past. (It is more Important than even, the coronary height.Mind you coronary height matters little if leaflet is long enough to reach the ostium , when TAVI flushed it with wall of Aorta.)
Intra procedural precautions(In small shallow roots)
Chimney Stenting: Prophylactic wire in the Left Main and park an undeployed drug-eluting stent. If any segment of TAVI tends to occlude deploy the stent.
BASILICA/Leaflet Splitting: This is used in ultra-high risk or valve-in-valve cases, use radiofrequency energy or mechanical cutting devices to lacerate the target aortic cusp before valve deployment, forcing it to part like a curtain instead of blocking the ostium.This is not an easy procedure as it may look. Prone for its own complication.
Post-Procedural & Long-Term Management
Dual antiplatelet therapy is critical . Routine echocardiography and follow-up CT angiograms to monitor for delayed coronary obstruction or stent deformation . Documenting the valve-stent alignment is encouraged for a possible future coronary interventions.
Planning a PCI with TAVI
Image source : Ref 2
PCI types in different types of valves. A) PCI with minimal stent protrusion due to limited space between the valve and the STJ. B) Adequate space between the valve and the STJ, allowing for the chimney technique. C) Valve-directed stenting from the coronary ostium towards the valve frame. D) PCI with minimal protrusion, as the coronary ostium is located above the valve. E) Coronary ostium located below the valve frame, with sufficient space between the valve and the STJ to perform the chimney/snorkel technique. F) Coronary ostium located below the valve frame, with limited space between the valve and the STJ; therefore, stenting is directed from the ostium towards the valve. BEV: balloon-expandable valve; PCI: percutaneous coronary intervention; SEV: self-expanding valve; STJ: sinotubular junction; TAVI: transcatheter aortic valve implantation
Final message
TAVI is a popular Aortic Intervention, but the risk of coronary obstruction is often underestimated by cardiologists, and it can happen during the procedure or in the long term; thus, preparedness is essential.
During physiology classes in medical schools, we are taught about the fundamental difference between cardiac and skeletal muscles. While skeletal muscle gets fatigued, cardiac muscle is unique in that it never takes rest, still it has the capacity not to get fatigued. We also learn cardiac myocytes handle calcium ions in a totally different way and they can’t be tetanized.
Is that all really true?
The tachycardic cardiomyopathy
Here the cardiac muscle typically goes into short‑term or long‑term fatigue due to ATP depletion or exhaustion. Many recover; some hearts do not recover. So, what we learnt in physiology classes is not indeed entirely right. Physiological rules apply only within the physiological limits.
Cardiac muscle paralysis
Like skeletal muscle, cardiac muscle does paralyze when the heart rate becomes too rapid as in VT and finally ends in cardiac convulsions called ventricular fibrillation. We are not clear whether stress cardiomyopathy and resulting ballooning of the apex is an expression of cardiac muscle fatigue and weakness.
Final message
It looks like cardiac muscle do get fatigued like skeletal muscle, but only beyond physiological limits. The reality and the clinical implication is more tricky as this physiological limit can vary very much between individuals. We need to assess and assist such hearts by metabolic means and to give adequate rest to recover. In cardiac failure, exercise prescription can either be useful or counterproductive in chronically fatigued hearts.
Postamble
If the heart fails to relax in diastole,(the short time it gets in between two contraction) it results in diastolic dysfunction. We have always looked diastolic dysfunction in a hemodynamic perspective. It is time , we need to look into the metabolic and biochemical and molecular basis of LV relaxation.
Human myocardium does not read hospital sign boards . It simply doesn’t bother whether thrombolysis is done in a moving van or a stationary room . When confronted with a life threatening emergency , all that it demands is quickness with which it is administered. Yet, in modern interventional cardiology, a same thrombolytic drug transforms from a life-saver into a forbidden clinical error, depending on whether it was injected in an moving ambulance or in the emergency Department.
This is the comical, yet tragic, irony of modern STEMI care.
Pre-hospital lysis is celebrated as a great strategy , while ultra fast in hospital lysis even within the “golden hour” is frowned upon as low-quality treatment.
At the heart of this paradox lies , the cult like status of primary PCI .It is true, pPCI has been etched as the gold standard of ACS care. However, most of the experienced cardiologist* know its perceived supremacy is not absolute ,largely attributed to the seductive power cath lab . (* Few have the courage to admit it )
Respect the myocardium not the cath lab
The efficacy thrombolysis is strictly a function of time, not geography. Landmark data from the CAPTIM trial explicitly demonstrated that when thrombolysis is administered within this early window, mortality rates are equivalent, and in some subsets superior, to immediate pPCI.
The current system of care willingly accepts this when a paramedic administers the drug but reprimands a physical if he does the same in his CCU .Why ? We seem to suffer from a misplaced academic arrogance that demands , fate of every coronary event must be decided only in cath lab. Any thing else is considered as deviation from the standard of care
Final message
It is time to change how we use the terms “pre-hospital” and “in-hospital” thrombolysis and replace them with a simple terminology . Symptom to Reperfusion Time. If a patient presents to a pPCI-capable center within the first hour standalone, ultra-fast ER lysis should be made an established, protocol equivalent to pre-hospital care, which is at equipoise with (un)disputed gold standard of pPCI as per the landmark study of CAPTIM.
Postamble
It is heartening to note In-hospital thrombolysis continues to be dominate mode of reperfusion at any point of time, inspite of the negativity surrounding it. Can we take this as a proof of real mettle of pPCI ?
We are taught embryology of the heart, right from the first year , when we enter the medical school.We learnt about various holes of the heart in a sincere way .After 15 years or so , it is fascinating for a fellow to become full-fledged structural interventional cardiologist , and close an ASD with an Amplatzer device with absolute ease.
Can’t ignore the basics
Meanwhile, how many of us are aware, there is a big disconnect between basic science and the cath lab cardiology. When I ask my fellows, what is the origin ostium secundum ASD ? majority come with wrong answer. Very few of us have time and interest to go deep into the different layers of IAS development. Now, let us be aware, there is a host of errors in the way we have understood the embryological basis of ASD.
The first one : The most common type of ASD, what we call, it as OS ASD , Is actually a defect in septum primum.
The second is OP ASD is not due to defect in septum primum , but due to defect in AV cushion.
The third : The so called sinus venosus type of ASD is not an ASD at all, where IAS is totally intact.it is just an vascular Unroofing, between PV and SVC.
The fourth and an ultimate shocker Embryologically, there may not be anything called true septum secundum, it is just interatrial fold, we named it as septum secundum and include it as apart of part of IAS .
The traditional Name
What it Sounds Like
What it Actually Means Anatomically
Ostium Secundum ASD
A defect in the septum secundum.
A hole or deficiency in the septum primum (the fossa ovalis floor).
Ostium Primum ASD
A defect in septum primum, that comes lower in IAS than OS ASD
It is an endocardial cushion defect at the AV junction , to precise they are defects of IAS rather Partial AVSD).
Sinus Venosus Defect
A true hole within the interatrial septal wall.
An unroofing/missing wall between the pulmonary vein and a vena cava (SVC or IVVC) outside the true septum.
Septum Secundum
An ingrowth of septal tissue left of septum primum , that forms the upper part of IAS
It is not true component of IAS. It is a thick in-folding of the outer roof wall (interatrial groove) pushed downwards and incompletely fuse with septum primum, forming the fossa ovalis in the process.
Final message
A hole is a hole is a hole.If you have a device close it, can’t waste time to bother about the origin of it . May be you are right as a restless Interventional cardiologist. 150 years of congenital heart disease , thousands of literature and advanced imaging ,interventions, can’t be Ignored. Let us be aware of the reality of embryology and how we are still following the old cheat sheets .Fellows please make a note of it.
Learning anatomy is foundational first step in the pathway to become a great clinician. This post is written to address a potential nomenclature issue in cardiac anatomy .
What constitutes Aortic annulus.?
“Aortic annulus” by default conveys a discrete, planar, circular ring. However, from a macroscopic and histological perspective, a distinct, single-plane collagenous ring does not exist at the base of the aortic valve. Rather, aortic annulus is a complex, three-dimensional , Morpho-anatomical functional zone spanning the ventriculo-aortic junction. This brings the aortic leaflets to be arranged in a crown-like formation that crosses multiple spatial planes. The lowest points of these attachments (the nadirs) dip into the left ventricular outflow tract, while the highest points (the commissures) extend superiorly to anchor at the sinotubular junction.
Can anyone see a single plane of Aortic annulus in the above Image ? Note the leaflets , pan whole area from the virtual ring to the ST junction making the annulus a well secluded zone with from ST junction to the virtual lower ring. This aortic annular zone has clear cut boundaries, the inferior border is formed by lowermost insertion points of the aortic valve leaflets. (Which just above the virtual ring formed by sinus of valsalva)
Why the misconception ?
The misconception of a flat aortic annulus came from extrapolation of AV valve anatomy to the semilunar valves. In the mitral and tricuspid positions, the leaflets anchor to a continuous, planar fibrous skeleton. Consequently, their hinge lines and leaflet planes remain the same in a reatively single plane throughout the cardiac cycle.
Systolic and diastolic disconnect
This complex anatomy of aortic annulus also results in a clear disconnect between systole and diastole. During systole, the aortic leaflets open vertically like flushed doors, against the sinus walls , while the basal plane vanish.Conversely, during diastole, the leaflets fall medially and down to meet at the center, creating a horizontal plane of coaptation.
Timing of measurement of aortic annlus
We are asked to measure the aortic annulus in peak systole. Ironically at this point of time , every measurement becomes virtual in the aortic annular zone. At least in diastole, the so called virtual lower end becomes real with leaflets hanging down forming a point of reference.
TAVI and Aortic annulus measuerment
The measurement of the aortic annulus has become essential due to the rise of TAVI, as CT scans accurately define the annulus compared to echocardiography, revealing the distinct height of the aortic annulus that was previously unrecognized. read below, for all the relevant measurements before doing a TAVI.
Newer TAVI engineering designers intentionally utilizes the entire vertical distance of the aortic root (from the leaflet nadirs to the ST junction) to anchor, seal, and position leaflets across different spatial planes to optimize physics and hemodynamics
Final message
The perception of aortic annulus as a single anatomical plane in our minds is very firm and it is due to the flaw in the way we learned cardiac anatomy. To make things right, we need to change aortic annulus as the “aortic annular zone” in anatomical literature. This change must be made at the earliest, right from the first clinical years of undergraduate education. Recognizing this is vital for understanding surgical or percutaneous repair or replacement of prosthetic valves.
Postamble (For the fellows)
When someone asks you what is aortic annular size, please ask them to confirm which dimension they are talking about. If they are surprised, teach them, there are distinct multiple horizontal (Maximal, minimal) and vertical distance for every annulus.(Which can correlate to a certain extent to the coronary height, the TAVI guys talk about)
de Kerchove L, El Khoury G. Anatomy and pathophysiology of the ventriculo-aortic junction. Ann Cardiothorac Surg. 2013;2(1):87-92. doi:10.3978/j.issn.2225-319X.2012.11.15
Aortic dissection splits the aorta into a true lumen (TL) and a false lumen (FL) at different planes of aortic media. True lumen often retains* all the three wall layers (intima, media, adventitia), providing structural stability. Conversely, the FL outer wall consists only of outer media and adventitia. This thin wall can be fragile. Persistent, un-thrombosed FL flow may maintain organ perfusion but it carries a risk of aneurysm or late rupture. The false lumen has less elastin, in long term more likely to to replaced with fibrosis. In spite of this , there are occasions were false lumen can by exploited for a good circulation. (Click here for more eloborate True vs false lumen difference)
*A significant portion of wall of true lumen faces the false lumen .So technically true lumen also lacks three layers in its entire 360 degrees. But the risk of rupture is internal not in the aortic wall.A comforting truth about false lumen.The fragility of false lumen is highly variable, depending on the thickness of media .However, adventitia , the toughest layer of of Aorta is always there to limit the risk of rupture in the outer curvature.
Situations where false lumen Stenting is only way out.
While standard endovascular repair aims to stent the TL and obliterate the FL, stenting the FL itself is utilized in two distinct scenarios:
Intentional Organ Salvage: In chronic or severe dissections, vital branch arteries may arise solely from a dominant FL. If the TL is too crushed or severely calcified (or porcelain like ), we need to intentionally stent the FL to preserve critical organ perfusion.
The STABILISE Technique: This aggressive strategy uses a TL stent followed by heavy-duty balloon inflation. The balloon deliberately breaks the internal dissection flap, obliterating the FL space and fusing both channels into a single, stable lumen.(Ref 2)
Inadvertent false lumen stenting
This is more common than we realise.Some times it is not never recognised ,if the entry and exit paths are clean. But more often it creates immediate hemodynamic issues.A guidewire can accidentally enter the dynamic FL . Deploying a stent here can catastrophically crush the TL, requiring immediate rescue fenestration or secondary TL stenting to restore flow.
Conclusion
Identifying entire morphology of true and false lumen is critical. Restoring true lumen flow, and trying to obliterate false lumen is the default strategy in majority of aortic dissections. However, it is good to recognise , false lumen stenting is not forbidden, if situations demand. It can be life-saving in some complex anatomy or acute organ malperfusion.
Reference
Simring D, Raja J, Morgan-Rowe L, Hague J, Harris PL, Ivancev K. Placement of a branched stent graft into the false lumen of a chronic type B aortic dissection. J Vasc Surg. 2011 Dec;54(6):1784-7. doi: 10.1016/j.jvs.2011.05.053. Epub 2011 Jul 23. PMID: 21784607.
Hofferberth SC, Nixon IK, Boston RC, McLachlan CS, Mossop PJ. Stent-assisted balloon-induced intimal disruption and relamination in aortic dissection repair: the STABILISE concept. J Thorac Cardiovasc Surg. 2014;147(4):1240-1245. Available from: The Journal of Thoracic and Cardiovascular Surgery or via PubMed Central.
Resch TA, Kölbel T, Dias NV, Rohlffs F, Carpenter SW, Heidemann F, et al. Intentional false lumen stenting for complex chronic aortic dissection: te
We know south Asians (who constitute about 2 billion people) consistently develop premature and severe atherosclerosis despite largely normal or only mildly elevated LDL-C levels. This “Lipid Paradox” is driven by small dense LDL particles, elevated ApoB, high triglycerides, low HDL, and insulin resistance not classical high LDL cholesterol.
This reveals a fundamental flaw in the current LDL-centric model of atherosclerosis genesis. When one-quarter of humanity develops CAD without high LDL, we must question whether LDL reduction is the primary target or merely a convenient proxy. A broader focus on ApoB, metabolic health, and visceral fat may be more scientifically honest and cost-effective.
Further, HDL molecule has its own problems in being a savior. At a level more than 60 mg/dl, it loses its protective value; rather, excess dysfunctional HDL is harmful as well. Since we have failed to increase HDL by pharmacological means, LDL reduction has gained more attention.(Franczyk B Et all , 2021)
Forget the patient .. target the LDL
Yet, aggressive marketing promotes expensive drugs like, PCSK antagonists, SiRNAs like Inclisiran and ATP citrate blocker Bempedoic acid to target ultra-low LDL levels (<55 or <50 mg/dL) in a population where LDL-C is often a weak tentative target. The latest to join the LDL rat race is the VERVE* 102 yearly Injection , a dramatic temporary RNA editing drug by the pharma giant Eli lilly.
*VERVE-102 consists of a messenger RNA encoding an adenine base-editor protein and a guide RNA targeting PCSK9, which are encapsulated in a lipid nanoparticle incorporating N-acetylgalactosamine(NEJM 2026)
Final message
LDL is definitely one of the culprit in human Atherosclerosis , but it is very difficult to prove , it is a major, universal, risk factor in isolation.This is not mocking the science. This is true at least in our part of the world. To treat a South Asian patient exclusively on standard LDL lowering protocols and projecting it as villain de chief, is not a scientically sound cardiology practice.
Reference
Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic Cardiovascular Disease in South Asians in the United States: Epidemiology, Risk Factors, and Treatments: A Scientific Statement From the American Heart Association. Circulation. 2018;138(1):e1-e34.
Agarwala A, Satish P, Al Rifai M, et al. Identification and Management of Atherosclerotic Cardiovascular Disease Risk in South Asian Populations in the U.S. JACC Adv. 2023;2(2):100258.
Bilen O, Kamal A, Virani SS. Lipoprotein abnormalities in South Asians and its association with cardiovascular disease: Current and future perspectives. J Clin Lipidol. 2016;10(3):543-552.
Postamble
The word “wrong culprit” in the title is intentional. It actually means “not a primary culprit”
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Dr.S.Venkatesan MD 