CME INDIA Case Presentation Dr Deepak Gupta, DM, FESC, FSCAI, FACC, Director Cardiac Sciences Pulse Superspeciality Hospital, Ranchi.

CME INDIA Case Study:

50yr old male develops CVA while swimming in club at Varanasi, strong family history of stroke in young. He is diabetic, well controlled (hb1ac=6.5), non-hypertensive.


CT Brain shows anterior cerebral artery involvement. ECG-Normal, Echo-normal, Lipids – within normal range.

Treatment received

Thrombolysis within 60 minutes. Very good improvement except only few residual disability and some memory impairment. Soon goes back to normal activity.

He visits Ranchi later on to consult me as wanted to go Australia for vacation trip.

What to think at this Juncture?

  • Ischemic stroke may be caused by a variety of heterogeneous mechanisms, and secondary stroke prevention is optimized by targeting the most likely etiology of the preceding event.
  • There is accumulating evidence that occult atrial fibrillation accounts for a meaningful portion of cryptogenic stroke.
  • Risk Factors and Biomarkers for AF:
    • Systemic hypertension.
    • Obesity.
    • Sleep apnea.
    •  Enlarged left atrium.
    • Hyperthyroidism.
    •  Diabetes alcohol abuse.
    • Cigarette smoking.
    • Elevated Pro BNP.
    • Frequent premature atrial contractions.
    • Increased P wave dispersion on ECG.

Further Work Up done at Ranchi

Holter, Repeat echo (preferably TEE), and Coaglation Profile

  • Holter 1 week – No AF episodes.
  • TTE (trans thoracic echo) in VNS – Normal.
  • Coagulation profile – Mildly raised fibrinogen level.


  • Should we level it as cryptogenic stroke?
  • What therapy to prevent next stroke?

As cause of stroke not settled TEE (trans esophageal echo) was done:

It shows PFO (Persistent Foramen Ovale)

Contrast TEE was also done

Diagnosis of PFO

Suspicion of PFO

  • Transthoacic echo misses 50%.
  • TEE misses 10%.
  • Transcranial doppler – Most sensitive modality.

Quick Look at PFO

  • PFO an “innocent bystander?”
  • PFO is highly prevalent, found in approximately 25% of the general adult population.
  • The risk of stroke recurrence in patients with PFO and no other etiology identified is low, approximately 1% per year.
  • This stroke risk is generally lower than the stroke risk caused by other possible common stroke mechanisms.

High-risk PFO

  • Atrial septal aneurysm.
  • Hypermobility (phasic septal excursion into either atrium >10 mm).
  • PFO size (maximum separation of the septum primum from the secundum) > 2 mm.

Dilemma Unlimited

I advised for Closure of PFO but difference of opinion Cardiologist vs Neurologist existed. Could it be a diabetic vasulopathy?

It was very alarming.

Next repeat stroke in Ant Cerebral Artery after 2 months of 1st episode.

Referred to NIMHANS, Bengaluru

3 days discussion on this young patient

  • CT angiography (CTA) or MR angiography (MRA) of the head and neck vessels.
  • Repeat ECHO TEE.
  • Advised PFO Closure.

CME INDIA Learning Points:

  • In setting of PFO, time to retire cryptogenic stroke, better term to use PFO associated stroke in order to better diagnosis and ultimately treatment.
  • Aspirin and clopidogrel are usually given for 6 months but evidence for this is limited and practice has varied markedly between trials. Some operators preload patients with anti-platelets, but again the evidence for this is uncertain. Single antiplatelet therapy, usually clopidogrel 75mg daily is continued indefinitely.
  • The patient should undergo TTE prior to discharge and at 6 weeks to exclude pericardial effusion and device embolization.
  • Complete closure depends upon endothelisation of the device and can take up to 6 months after which time a repeat bubble study can be undertaken to confirm closure.
  • Cryptogenic stroke is defined as brain infarction that is not attributed to definite large‐vessel atherosclerosis, small‐artery disease, or embolism despite extensive vascular, serological, and cardiac evaluation.
  • Approximately one‐third of all ischemic strokes are considered cryptogenic.
  • The causal relationship between patent foramen ovale (PFO) and cryptogenic stroke has historically been controversial. Approximately 25% of the adult population has a PFO, and the condition by itself has not been shown to increase the risk of ischemic stroke.
  • Yet, the prevalence of PFO is significantly higher in patients with cryptogenic stroke; up to 40% of ischemic strokes without an identifiable cause have a PFO. This suggests that paradoxical embolism through a PFO may be implicated in a proportion of cryptogenic strokes.
  • Evaluation of patients with suspected PFO should start with a transthoracic echocardiogram (TTE) and administration of agitated saline bubbles.
  • The “bubble study” is best done in the standard apical 4‐chamber view. The timing of bubbles appearing into the left atrium is important to differentiate intracardiac from transpulmonary shunts. Intracardiac shunting is likely when bubbles appear in the left‐sided cardiac chambers within 3 cardiac cycles.

CME INDIA Tail Piece:

“PFOs don’t actually cause strokes, but they provide a portal through which a thrombus might pass from the right to the left side of the circulation Depending on whether the clot takes a right or left turn as it exits the heart, it can travel to the brain and cause stroke or TIA. Statistically speaking, the odds of this happening are low.”

May 19, 2020; 94 (20) Practice advisory update summary: Patent foramen ovale and secondary stroke prevention. Report of the Guideline Subcommittee of the American Academy of Neurology.

Major recommendations:

  • In patients being considered for PFO closure, clinicians should ensure that an appropriately thorough evaluation has been performed to rule out alternative mechanisms of stroke (level B).
  • In patients with a higher risk alternative mechanism of stroke identified, clinicians should not routinely recommend PFO closure (level B).
  • Clinicians should counsel patients that having a PFO is common; that it occurs in about 1 in 4 adults in the general population; that it is difficult to determine with certainty whether their PFO caused their stroke; and that PFO closure probably reduces recurrent stroke risk in select patients (level B).
  • In patients younger than 60 years with a PFO and embolic-appearing infarct and no other mechanism of stroke identified, clinicians may recommend closure following a discussion of potential benefits (absolute recurrent stroke risk reduction of 3.4% at 5 years) and risks (periprocedural complication rate of 3.9% and increased absolute rate of non-periprocedural atrial fibrillation of 0.33% per year) (level C).
  • In patients who opt to receive medical therapy alone without PFO closure, clinicians may recommend an antiplatelet medication such as aspirin or anticoagulation (level C).

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