What do I do if my patient on an antiarrhythmic goes back into atrial fibrillation?!

I had a patient recently who flipped from normal sinus rhythm into asymptomatic afib with RVR with heart rates into the 150s on post-op day 2. Classic. The twist is that she had been in sinus rhythm for years on flecainide prior to the surgery, and was still taking flecainide post-op. I was stymied: did her being on flecainide change management?  Answer at the end of the post!

The urgent question: do you need to cardiovert? The indications for cardioversion are still the same when a patient is on an antiarrhythmic: (1) unacceptable symptoms like syncope, CHF; (2) hemodynamic instability; (3) first episode of new afib within 48 hours (this did NOT apply to my patient because she had a history of afib). Cardioverting whether mechanically or pharmacologically with something like amiodarone carries the same risk of thromboembolism, so the next question should be…

Is the patient anticoagulated? Patients who flip from sinus into afib are at the highest risk of thromboembolism in the first 48 hours. Sometimes patients’ anticoagulation may be held, like in the perioperative period like for my patient. Try to make sure that if there are no contraindications to anticoagulation, it’s restarted.

Is there an underlying trigger? Lots of things can trigger afib: infection, PE, MI, fluid shifts, hyperthyroidism, postoperative stress, etc…If there is a trigger, treating it will make the afib better. Try to make sure there is nothing else going on that could be fixed.

If you are looking for specific discussions on different antiarrhythmics, check out this comprehensive review.

To return to my patient, the goal was still rate control. We decided that it was fine to continue her flecainide, and more than likely her rates would come down and she would convert back to sinus on her own. The biggest concern for her was that she was off anticoagulation. Two days later, she was still in afib, but her rates were in the 90s and she was back on apixaban.

Side note: many cardiologists advocate an antiarrhythmic “pill in pocket” for patients with infrequent afib. If they develop symptomatic afib, they can take the pill right then and there, which increases their chance of going back to sinus. However, if they are also on beta blockers, they should take the beta blocker first, as a medication like flecainide can have greater toxicity if it binds to receptors before the beta blocker does. Flecainide should always be combined with a beta blocker or other rate control agent, as one adverse effect is organization of the atrial rhythm so that the AV node can conduct 1:1 –> conversion of afib into atrial flutter with RVR (rates as high as 200s) which is obviously not sustainable.


How do I select an agent for afterload reduction in a patient with heart failure?

Afterload reduction has been recommended in the management of systolic heart failure since the 1980s. Afterload= arterial resistance as blood is pumped out of the left ventricle. The thought is that by reducing afterload, cardiac filling pressures are decreased, which is beneficial.

What agents reduce afterload? Anything that is an arterial vasodilator. (Venodilators decrease preload, which are thought to have a similar beneficial effect.)

  • Nitrates (venous>arterial vasodilators)
  • Hydralazine (most selective arterial vasodilator, in my experience this has been used the most)
  • Minoxidil (arterial vasodilator)
  • Lisinopril, captopril (about equal veno- and arterial vasodilators)
  • Diuretics (long-term arterial vasodilator)
  • In the ICU: nitroprusside, phentolamine, dopamine
  • Inotropes like milrinone (patients with advanced heart failure may be put on this palliatively)
  • Technically, the intra-aortic balloon pump (IABP) does, too!

What is the diagnostic accuracy of pulsus paradoxus for cardiac tamponade?

A classic Step 1 associations is: increased pulsus paradoxus=cardiac tamponade. But like everything in medicine, it’s not that simple. An abnormal pulsus paradoxus is not really sensitive or specific for cardiac tamponade. Pulsus paradoxus may also be present in patients with labored breathing, asthma attacks, pulmonary hypertension, constrictive pericarditis, PE, etc. This summary cites one report that “15% pulsus paradoxus in the face of relative hypotension was found in 97% of patients with moderate or severe tamponade and only 6% of patients with absent or mild tamponade.”

This review in Clinical Cardiology describes pulsus paradoxus as the “end of a spectrum” in cardiac tamponade, which frames it as what it is: an exam finding that if present, means that it’s more likely the patient is ALREADY in tamponade and you should act quickly…but just because it’s absent doesn’t mean the patient does NOT have tamponade.  This study reports that NHYA Class III symptoms (comfortable at rest but significant symptoms impairing function) were significantly associated the development of cardiac tamponade, which seems like it would be obvious, but can help in ambiguous cases. In my anecdotal experience, this is true, and relative hypotension, a narrow pulse pressure, and distended neck veins have been more sensitive for predicting tamponade.

NB: when trying to figure out if a pulsus paradoxus is abnormal, 20-30 mm Hg is considered high. But remember to take the pulse pressure into account! If the pulse pressure is narrow (like 110/90), then a pulsus of even 10 mm Hg might be abnormal and warrants immediate ultrasound.

What are the PCSK9 inhibitors?

There are two that are FDA approved: alirocumab (Praluent) and evolocumab (Repatha).

What is the biological basis of PCSK9 inhibitors?

LDL-R (for receptor) is found on the surface of hepatocytes. These receptors pick out LDL-c from the circulation, lowering the LDL level in the bloodstream. That’s a good thing!

PCSK9 is a protein that balances out the effect of LDL-R by binding to LDL-R and getting it degraded, thereby not allowing LDL-c to get reabsorbed. This means LDL levels may go up. (See this illustration and explanation) The PCSK9 inhibitors (mAbs) bind to PCSK9, which allows LDL-R to keep doing it’s job, and keep LDL-c levels low.

Are PCSK9 inhibitors effective? 

Yes. They are especially effective at reducing LDL levels when combined with statins. This review goes into exhaustive detail about trial data. However, no one knows for sure if they, like statins, reduce mortality from cardiovascular disease.

What caveats do I need to know about these drugs? 

  • Injected, not in pill form. This may be a barrier for some patients who either can’t (or won’t) inject themselves
  • These drugs are expensive! A year’s supply of evolocucamb is estimated to cost about $14,500. It’s unclear how much of that may be covered by insurance
  • The most common side effects are nasopharyngitis, congestion, and myalgia, but there are concerns about allergic reactions (it’s a monoclonal antibody) and cognitive impairment (subjective, but was reported in the phase III trials).
  • Patients with severe kidney and liver disease were excluded from studies, so if, for example, you have a patient with cirrhosis who wants to start one of these medications, talk with their hepatologist
  • Long-term studies on these drugs are lacking; there is a Cochrane review that reports that overall, follow up times for PCSK9 inhibitor studies have been short (26 months at the longest) and there have been few reported events.

Is is safe to give tPA/thrombolytics to someone who just underwent cardiac catheterization?

At my institution, we recently discussed a case of a patient with acute stroke in the setting of cardiac catheterization (right femoral access). The decision to push tPA was a tricky one, because he had just been cathed. When is it ok? When is it NOT ok?

Here are relative and absolute contraindications (respectively) for giving tPA:


As you can see, arterial puncture at a noncompressible site is a relative contraindication for tPA. So depending on where the puncture site was…the typical site for an arterial stick in a catheterization is between the bifurcation of the SFA and PFA and the branching point of the inferior epigastric artery. Typical site=compressible, “high stick”=noncompressible. If there is a “high stick,” tPA will confer a much higher risk of RP bleed and hemorrhage, and should be avoided.

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What is a “MIBI scan” and who should get one?

“MIBI” is short for sestamibi, a mildly radioactive compound that is used to perform nuclear scans. Sestamibi = technetium-99 = methoxy-isobutyl-isonitrile.

Thallium = TI 201 is another radioactive agent that is used in myocardial perfusions scans.

Either of these agents can be used to perform a nuclear myocardial perfusion rest-stress test, which may also be referred to as single photon emission computed tomography (SPECT). They are equally sensitive in detecting areas of ischemia or scarring. Thallium may be more sensitive for detecting viable myocardium because it is lower energy and redistributes in tissue; it does not remain fixed in myocytes. However, it also has a much longer half-life (73 hours opposed to 6 hours for sestamibi).

These radioactive agents that are used to image the heart are different from the pharmacological agents that are used to stress the heart. Pharmacological agents include adenosine, dobutamine, persantine.

Stress modalities: exercise, pharmacological (*note the terminology is different than in the borrowed image below)

Imaging modalities: EKG, ECHO, nuclear, CT

Imaging modality
Stress modality EKG ECHO Nuclear
Pharmacological (adenosine, dobutamine, persantine)    

You can mix and match any of these to create a stress test that fits your patient’s condition/contraindications best!



How should I interpret pulse pressure?

How do pulse pressure and mean arterial pressure differ, and how are they related? 

Mean arterial pressure (MAP)
= 1/3*(systolic blood pressure) + 2/3*(diastolic blood pressure) 
= cardiac output [heart rate*stroke volume] * systemic vascular resistance 
= ¼ diastolic blood pressure + 0.4*(pulse pressure). 

MAP is an important way to measure blood pressure; MAP is what we use to titrate pressors and measure perfusion. However, consider the case of person #1 with a BP 130/80 and person #2 with a BP 160/60. Both of them have a MAP of 100 mm Hg by the first calculation, but clearly, the blood pressures are different–what is different is the originating pressure from the left ventricle, and pulse pressure correlates better with this. This chapter explains the factors that contribute to pulse pressure elegantly, but the simple equation is:

Pulse pressure (PP) = systolic blood pressure – diastolic blood pressure

What is a “high” PP and what is a “low” PP, and what do they signify?

There is no specific cut-off that I could find. However, if you think about 120/80 as a “normal” blood pressure, that indicates that a “normal” PP=40. The study cited below uses a cutoff of <30 mm Hg as a “low” PP. Therefore, it’s reasonable to think that a “high” PP is >50 and a “low” PP is <30.

Traditionally, we have been warned against high pulse pressure. Why? High PP is associated with increased cardiovascular death, as well as CAD, MI, and heart failure, because it signifies either/and a high systolic blood pressure and low diastolic blood pressure. In addition to heart failure, other conditions associated with a high PP include severe anemia, sepsis, thyrotoxicosis, aortic dissection, aortic regurgitation, neurological conditions (i.e. hemorrhage) or AVMs (things that might cause a high output heart failure state).

However, low PP can also be dangerous. If you think about it, someone with a systolic and diastolic blood pressure that are almost the same is in a “low flow” state; their blood pressure demonstrates they can’t push blood forward effectively. This study is one report about an association between low PP and cardiovascular death in patients with heart failure, specifically, advanced heart failure (NYHA Class III-IV). In addition to advanced heart failure, other conditions associated with a low PP include cardiogenic shock, tamponade, and severe aortic stenosis. 

Bonus question: what is “true MAP” and how is it calculated? “True MAP” is direct measurement of pulsatile flow…think about that…it’s measured through tonometry, usually of the brachial artery, which involves placement of an arterial line.