Moffitt Cardiology Pearls 10/10/17 – Congenital Heart Disease and SVC Syndrome

Thank you so much to Nick and Matt for presenting the case of a young man with a history of congenital pulmonary atresia and hypoplastic RV decades status post a bidirectional Glenn procedure coming in with shortness of breath and chest pain. The patient was found to have a severely dilated aortic root with resultant aortic insufficiency and severe pulmonary hypertension.

 

KEY PEARLS:

  1. When assessing a patient with congenital heart disease, it is VITAL to obtain records outlining the pathophysiology and previous procedures in order to understand their current physiology and what might go wrong.
  2. As Anne Thorson shared with us, in a patient with congenital heart disease who was previously doing well and then decompensates, ALWAYS consider the possibility of infection (particularly endocarditis) as the cause.
  3. SVC syndrome is a clinical diagnosis – see some physical exam features below.

    Cyanotic Congenital Heart Lesions: There are 5 main lesions, often called the “5 Ts”, of congenital heart defects that can result in cyanosis at birth or in the neonatal period. Most of these conditions will require intervention within the first months of life.

     

    Here’s a review on cyanotic congenital heart disease in adults. Of note, it’s from 1975… my guess is many things have changed since then and we see significantly more adult survivors of congenital disease.

Pulmonary atresia and hypoplastic RV is NOT typically a cyanotic heart lesion. However, the small RV + atretic pulmonic valve can lead to a volume and pressure overloaded state on the right side the heart. The Bidirectional Glenn Procedure reduces blood flow to the hypoplastic RV (thus offloading the pressures) by diverting the SVC directly into the pulmonary arteries. Blood return from the IVC continues to enter into the RA.

 


While we most commonly see SVC Syndrome in the setting of extrinsic compression or internal invasion of the SVC in malignancy, remember that there are multiple other risk factors as well!

Risk factors for SVC syndrome:

  • Thoracic mass – lung cancer, lymphadenopathy, lymphoma, teratoma, thymoma
  • Vascular disease – aortic aneurysm, vasculitis, AV fistula
  • Scarring or Fibrosis – related to chronic infection (like histo as Harry mentioned or tuberculous mediastinitis as described by Schechter in 1954), radiation, or instrumentation
  • Cardiac causes – pericarditis, atrial myxoma OR, as in this case, severe pulmonary hypertension in patient whose SVC connects directly to the pulmonary veins!
  • Clot – with or without underlying malignancy or central venous catheter

Here’s another, more recent, review of SVC syndrome, describing the pathology, risk factors, diagnosis, and management.

Harry mentioned Pemberton’s sign, described in the linked NEJM images in Clinical Medicine article. Below are 2 YouTube videos showing the classic finding:  signs of SVC syndrome brought on by extending the arms over the head. The second is quite dramatic.

1) https://www.youtube.com/watch?v=r1dkasbE7v8

2) https://www.youtube.com/watch?v=m_ZecWGnb2A

 

Evernote: https://www.evernote.com/shard/s462/sh/d5befae6-e090-4f3e-ab15-7dfa8ed3e73a/6e88cb495f580e320334ed1c2932afb5

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Moffitt Pearls 10/9 – Polyarthritis

Key Pearls:
1)  There are a number of ways to approach arthritis including time course (acute vs. chronic), # of joints affected (mono vs. oligo vs. poly), size of joints affected (small vs. large), and symmetry.  See below for more about the DDx based on # of joints affected.
2) Arthritis vs. arthralgia?  Look for evidence of articular inflammation on the physical exam!  The key finding is synovitis.
3) The positive LR for synovial fluid WBCs >100K is 28 for septic arthritis! This was published by some of our very own (see below)!
4)  The seronegative spondyloarthropathies consist of ankylosing spondylitis, IBD-associated arthritis, psoriatic arthritis, reactive arthritis, and undifferentiated spondyloarthritis.

Check out this fantastic post from Grant Smith on Septic Arthritis and Reactive Arthritis!

 
Approach to Arthritis by # of Joints affected:
 

Monoarthritis (1 joint affected):

  • Infection (Staph, GC can be either mono or poly)
  • Crystal Arthropathy (gout, CPPD)
  • Rheum disease (RA, SLE, sarcoid, spondy)
  • Inflammatory osteoarthritis
  • Trauma/Hemarthrosis
  • Tumor (giant cell tumor, sarcoma, metastasis)

Oligoarthritis (definition varies:  at least 2 and up to 3 to 5) and Polyarthritis (at least 4):

  • Infection (GC, Lyme, endocarditis, viral)
  • Crystalline
  • Rheum disease (RA, SLE, sarcoid, ankylosing spondylitis, psoriatic, IBD, poly/dermatomyositis, vasculitis)
  • Inflammatory osteoarthritis
  • Post-infectious/reactive
  • Other systemic disease: FMF, malignancy

Migratory Arthritis:

  • Rhematic fever
  • Infective endocarditis
  • HSP
  • Serum sickness
  • Viral arthritis
  • Septicemia (staph, strep, mening/gonococcal)
  • Pulmonary infection: mycoplasma, histoplasmosis
  • Lyme disease
Discriminating Factor
Possible Diagnoses
Temperature >40.0 C
Still’s disease, bacterial arthritis, SLE
Fever preceding arthritis
viral arthritis, lyme disease, reactive arthritis, Still’s disease, endocarditis
Migratory arthritis
Rheumatic fever, gonococcus, meningococcus, viral arthritis, SLE, acute leukemia, Whipple’s disease
Effusion disproportionate to pain
TB arthritis, endocarditis, IBD, GCA, lyme disease
Pain disproportionate to effusion
Rheumatic fever, FMF, acute leukemia, AIDS
Positive RF
RA, viral arthritis, TB arthritis, endocarditis, SLE, sarcoidosis, systemic vasculitis
Morning stiffness
RA, PMR, Still’s disease, some viral and reactive arthritis
Symmetric small joint
RA, SLE, viral arthritis
Leukocytosis (>15K)
Bacterial arthritis, endocarditis, Still’s disease, systemic vasculitis, acute leukemia
Leukopenia
SLE, viral arthritis
Episodic recurrences
Lyme disease, crystal-induced arthropathy, IBD, Whipple’s disease, FMF, Still’s disease, SLE

From the JAMA Rational Clinical Exam 2007 Article, “Does This Adult Patient Have Septic Arthritis?”, by our very own Mary Margaretten and Jeff Kohlwes:
  • Summary LRs for Synovial Fluid studies:
    WBCs >100K 28
    WBCs >50K 7.7
    WBCs >25K 2.9
    PMNs > 90% 3.4

Seronegative Spondyloarthropathies:  Group of conditions linked by common clinical features and immunopathologic mechanisms. Distinguished from one another usually on basis of history and clinical findings.  “Seronegative” implies RF negativity.  All subtypes involve  the axial skeleton.  Extra-axial involvement, such as uveitis, calcaneal enthesitis or peripheral arthritis can occur in all subtypes.

  • Ankylosing spondylitis – 90% HLAB27 +
  • Psoriatic arthritis – 60% HLAB27 +.
  • Reactive arthritis – 85% HLAB27 +
  • IBD-associated or Enteropathic arthritis
  • Undifferentiated spondyloarthritis – no definite radiologic signs of sacroiliitis

SFGH Morning Report 10.6.17 – Cirrhosis – HCV Treatment and altered mental status

Thanks Dan for presenting an interesting case of a middle age man with HCV cirrhosis c/b HCC in the ICU after a motor vehicle accident with altered mental status, hyperkalemia, and volume overload.  Dr. Cello gave us some awesome pearls!

Learning Pearls

  • Of all the causes of cirrhosis there is one that will not progress to HCC: Congestive hepatopathy from heart failure
  • There is no role for beta-blocker treatment to prevent recurrent variceal bleeds after banding has been performed because the varices have a very low incidence of bleeding.  These patients may have upper GI bleed from other causes (gastritis, PUD, portal hypertensive gastropathy)
  • Treating individuals with HCV who are actively using drugs is part of the End Hep C SF Initiative! Patients should be counseled about the risk of re-infection
  • There are 5 reasons a cirrhotic will have worsening hepatic encephalopathy: increased gut protein load, infection, drugs, azotemia, or hypokalemia

 

Physical Exam in cirrhosis

  • Spider angiomata: the number and size of spider angiomata correlate with the severity of liver disease
  • Nail findings
    • Muehrcke nails = horizontal white bands
    • Terry’s nails = proximal 2/3 of the nail bed is white and distal 1/3 of nail bed is red
      • This is different from half-and-half nails seen in renal failure where the proximal 1/2 of the nail bed is white and the distal 1/2 of the nail bed is red
    • Both are due to hypoalbuminemia
  • Per Dr. Cello: A cirrhotic liver from alcohol is often big and feels like cooked ham whereas a cirrhotic liver from viral causes is often small and not palpable below the costal margin

Treatment of Varices

  • Pre-primary prophylaxis: Preventing variceal bleed by preventing varices.
    • Current goal is to treat underlying cause of cirrhosis leading to portal hypertension.  There is no data suggesting beta-blockers can prevent the developemnt of varices
    • We should continue screen patients with cirrhosis for varices
  • Primary prophylaxis: Preventing variceal bleeding by treating varices
    • Can treat with beta-blockers or endoscopic variceal ligation. Studies have shown similar efficacy
  • Beta-blockers reduce portal hypertension by decreasing portal venous inflow
  • Variceal ligation should be repeated until the varices are obliterated.  After they are obliterated they have a low risk of re-bleeding.

 

Treating HCV in IVDU

  • If the goal is to eliminate HCV then we need to treat the population most affected
  • Studies have shown successful (~95%) sustained virologic response in individuals treated with the direct-acting antivirals even when actively using drugs.
  • After treatment positive antibodies do not project against from re-infection
  • Reinfection rates in perviously cured individuals using drugs are ~5-10 per 100 person-years
  • SFDPH is actively treating individuals using drugs as part of their End Hep C SF Initiative

 

5 causes to look out for in a patient with hepatic encephalopathy

  • Protein load in the gut either from diet but more commonly from GI bleed
  • Infection
  • Drugs – especially drugs that have their first pass through the liver such as benzos
  • Azotemia
  • Hypokalemia worsening uremia

 

 

VA Ambulatory Report 10.4.17 – Nephrotic Syndrome

Thanks to Akshai for presenting an interesting case of a 41 yo F with subacute bilateral leg swelling found to have nephrotic syndrome in the process of being evaluated for the underlying cause.

 

Pearls

  • Proteinuria can be broken into 4 causes: Overflow, glomerular, tubular, post-renal
  • When concerned about a glomerular process use your clinical findings and UA to help you determine if the picture is more consistent with nephritic vs. nephrotic
  • Nephritic Syndrome is often diagnosed with lab tests whereas nephrotic syndrome usually needs a biopsy to confirm the underlying cause
  • Treatment of nephrotic syndrome: ACEi/ARB for proteinuria, loop diuretic and salt restriction for edema, statin if hyperlipidemia does not resolve, warfarin if thrombosis.

 

What is the usefulness of BNP for lower extremity edema?

  • Breathing Not Properly Study: In a patient presenting with dyspnea a BNP cut off of > 100 can be helpful in determining heart failure over pulmonary cause of dyspnea
  • The ACC/AHA 2017 Focused Update gives a Class I recommendation for measurement of BNP in patients presenting with dyspnea, to support a diagnosis or exclusion of HF.
  • No studies have looked at BNP in a patient presenting with lower extremity edema as a predictor for heart failure
  • Can be elevated for a variety of reasons:  renal failure, cirrhosis, sepsis, anemia, stroke, OSA, PE and more.

 

Causes of Proteinuria (Forgive my powerpoint nephron drawing!)

Screen Shot 2017-10-06 at 10.10.50 AM.png

Nephritic vs. Nephrotic?

Disease of the glomerulus can be nephrotic or nephritic.  Use your clinical findings and UA to help you differentiate.

  Clinical Findings UA and urine sediment Findings Histology Findings
Mild Nephritic Asymptomatic microscopic hematuria and proteinuria

Occassionally gross hematuria

RBCs, dysmorphic RBCs, RBC casts

Mild proteinuria

Inflammatory lesions in less than one half of glomeruli
Severe Nephritic Edema

HTN

Renal Insufficiency

RBCs, dysmorphic RBCs, RBC casts

Heavy Proteinuria (>1.5g/day)

Diffuse glomerular disease
Severe Nephrotic Hyperlipidemia

Edema

Thrombotic disease

Heavy proteinuria (oftenr >3.5g/day)

Few casts or cells

Varies based on underlying cause

 

Nephrotic Range Proteinuria work-up for the PCP:

  • Send ANA, A1c, HIV, RPR, and Hepatitis serologies.
  • Refer to renal for likely renal biopsy.
  • Renal biopsy is often needed in adults whereas children are often treated with empiric steroids for presumed minimal change disease.

 

Treatment of Nephrotic Syndrome

  • Proteinuria
    • The degree of proteinuria is a predictor of renal failure. Treatment can reduce progression.
    • ACEi/ARBs – BP effects are immediate but proteinuria effects can take days-weeks
  • Volume Overload:
    • Due to sodium retention (not oncotic pressure from protein loss)
    • Diuretics; Slow diuresis to prevent hypovolemia, start with loop diuretics but may also need thiazide diuretics
  • Hyperlipidemia
    • Often reverse when underlying cause is treated and reversed
    • Most patients will need statin
    • Dietary modification does not help
  • Hypercoagulability
    • More common in membranous nephropathy
    • If thrombosis, treat with warfarin
    • Unclear if prophylactic anticoagulation benefit outweighs risks, practice varies amongst nephrologists
  • Treat underlying cause if identified

ZSFG AM Report Pearls 10/4/2017: Sarcoidosis

Thank you to our team at ZSFG for presenting the case of a patient with sarcoidosis who presented with a history of falls, weight loss, and shortness of breath that brought up some questions about the basics of sarcoidosis. Check out the post below about some basics on sarcoidosis.

SARCOIDOSIS:
Pathophysiology:
  • Fundamental abnormality is formation and accumulation of granulomas (compact, centrally organized collections of macrophages and epithelioid cells encircled by lymphocytes).
  • About 20-25% of patients will develop pulmonary fibrosis due to matrix metalloproteinases
Clinical Features:
  • Often first seen on CXR for another reason
  • Fatigue, night sweats, and weight loss are common
  • Lofgren’s Syndrome: arthritis, erythema nodosum, bilateral hilar adenopathy
  • 2/3 of patients have remission within a decade after diagnosis with few or no consequences
  • 1/3 of patients have unrelenting disease
Diagnosis:
  • Unless presenting with classic Lofgren’s syndrome, typically need to have a biopsy specimen demonstrating noncaseating epithelioid-cell granulomas in the absence of organisms or particles.
    • Should biopsy from easiest access point (skin, peripheral lymph nodes, lacrima glands)
    • Sometimes, you may still need a bronchoscopy to get lung tissues
  • Need to rule out other infections (i.e. TB, bacterial cultures)
  • There is no value to checking a serum ACE level:
Organ Involvement:
  • Pulmonary: can present with a restrictive spirometry pattern (underlying fibrosis), pulmonary HTN
  • Cutaneous: can be disfiguring can be macules, papules, plaques and erythema nodosum
  • Liver/Spleen: typically clinically silent liver problems, but can include liver failure
  • Neurologic: involved in 25% of patients on autopsy, 10% clinically. MRI with gadolinium is useful for detecting involvement. Complications common to uncommon:
    • Cranial-nerve palsies
    • Headache
    • Ataxia
    • Cognitive dysfunction
    • Weakness
    • Seizures
  • Optho: anterior uveitis most common manifestation
  • Cardiac: Typically cardiomyopathy, can also present with tachy- or brady-arrhythmias. Diagnosis helped with MRI with gad and PET scanning to aid in dx (biopsy is limited b/c of the patchy nature of disease).
  • Renal: Can have hypercaliuria and renal calculi
  • Bone: Bony lesions can be seen throughout the skeleton, often confused
Treatment:
Treatment for Sarcoid

Sources:

  • Iannuzzi MC et al. (2007). Medical progress – Sarcoidosis. NEJM 347:2153-2165.

Evernote:

  • Sarcoidosis: https://www.evernote.com/shard/s509/sh/ff61b59b-6f75-456d-b99d-972fa8a4c790/e83ad7376c5ec6e2f8d33d64c9528ddc

 

Moffitt Pearls 10.6.17 – Thrombocytopenia, TTP, HUS

Thank you, Marko and Brad, for presenting a fascinating case of an older male presenting with fatigue and jaundice found to have profound thrombocytopenia, anemia, and AKI concerning for TTP!

Key Pearls

  1. The approach to thrombocytopenia can be organized by decreased production, increased consumption, and sequestration.
  2. TMA vs MAHA? What’s the difference again?? Microangiopathic hemolytic anemia refers to non-immune hemolysis (i.e. Coombs-negative hemolysis). As a result, you see schistocytes on blood smear. Thrombotic microangiopathy is a specific pathologic abnormality in the walls of arterioles and capillaries that lead to microvascular thrombosis. Not all MAHAs are a result of a TMA, but nearly all TMAs will cause MAHAs.
  3. There’s a new scoring system used to predict TTP – The PLASMIC score – you can use this to help determine when to start plasma exchange in a patient while you’re waiting for the ADAMTS13 to return.

Approach to Thrombocytopenia:

  • Decreased Production
    • Bone marrow process – can further guide ddx based on bone marrow biopsy
      • Hypocellular – aplastic anemia, MDS, drugs, alcohol, cirrhosis
      • Hypercellular – MDS, leukemia, megaloblastic anemia
      • Marrow Replacement – myelofibrosis, malignancy, granulomatous disease
    • Megakaryocyte process – most commonly EtOH use, as alcohol is a direct megakaryocyte toxin. Usually won’t get lower than ~100 without a secondary process as well.
  • Increased Destruction or Consumption
    • Immune-mediated
      • Primary: ITP
      • Secondary: infection, lupus, APS, lymphoproliferative disease, drugs (heparin!, antibiotics, H2 blockers), alloimmune
    • Non-Immune-mediated
      • MAHA, Plavix, vasculitis, HELLP, CVVH
  • Sequestration – splenomegaly – often from portal HTN

 


Approach to a Suspected TMA (from UpToDate):




The PLASMIC score

Published in the Lancet Haematology earlier this year, the PLASMIC score is a model that uses 5 independent variables to predict ADAMTS13 deficiency.  This model was developed in a cohort of 214 patients with thrombotic microangiography, of which 29% had TTP.  It was subsequently validated in 2 different cohorts.

  • Plts <30
  • Cr <2
  • INR < 1.5
  • MCV <90
  • Presence of hemolysis

Citations:

  1. Bendapudi PK, Hurwitz S, Fry A, Marques MB, Waldo SW, Li A, Sun L, Upadhyay V, Hamdan A, Brunner AM, Gansner JM, Viswanathan S, Kaufman RM, Uhl L, Stowell CP, Dzik WH, Makar RS. Derivation and external validation of the PLASMIC score for rapid assessment of adults with thrombotic microangiopathies: a cohort study. Lancet Haematol 2017.
  2. Jamme M, Rondeau E. The PLASMIC score for thrombotic thrombocytopenic purpura. Lancet Haematol 2017.

Evernote: https://www.evernote.com/shard/s462/sh/ea34eab3-06e4-4541-8664-b508bf3ab3ee/f0669d43862b43e7f513d48b1324aa8e

 

VA ICU Report 10.6.17: Pseudomonas double-coverage + post-arrest neurologic prognostication

Case summary: We discussed the case of 83M with PMH ESRD on HD, CAD s/p CABG, AIN on prednisone, who had a PEA arrest secondary to hypoxemia in the setting of multifocal pneumonia, who developed post-arrest myoclonus and was ultimately transitioned to comfort care. Thanks to Jill Goslinga, Neuro intern extraordinaire, for bringing up tons of great questions and pearls.

Top pearls: 

  1. Data support double-coverage (beta-lactam and aminoglycoside) for Pseudomonas in patients who are critically ill and at risk for multi-drug resistant organisms. Once sensitivities are known, you can narrow appropriately.
  2. Although neurologic prognostication is extremely variable, some 72H coma exam findings are predictive of poor neurologic outcome. These include absent or extensor motor response on day three and/or absent pupillary or corneal reflexes on day three.
  3. James Frank reminded us that nodules on a chest CT should make you expand your infectious differential beyond classic bacterial pathogens, particularly in immunocompromised patients– think carefully about mycobacteria (tuberculous and nontuberculous), endemic fungi (histo, cocci), and (rarely) PCP.

Pseudomonas double-coverage: just the facts

  • These are pearls I’ve learned from Jen Babik’s fantastic “Fever in the ICU” lectures.

Why do we talk about “double-coverage” for Pseudomonas?

1. Concern about resistant Pseudomonas: give 2 ABX EMPIRICALLY to expand the spectrum.

2. Idea of synergy between 2 active ABX: usually beta-lactam + (aminoglycoside or FQ).

  • 2012 metaanalysis showed NO mortality benefit, including for septic shock or neutropenic patients

3. Hope that 2 ABX prevents development of resistance.

  • No evidence that combination therapy prevents development of resistance and may increase superinfection rate.

…So when should we double-cover?

  1. In critically ill patients (like this patient) who have risk factors for multi-drug resistant organisms, consider empiric coverage with 2 ABX with anti-pseudomonal activity. Then narrow pending cultures and susceptibilities.
  2. Check your local sensitivities: the most recent SFVA Pseudomonas sensitivities from 1/2017 (non-urine and urine) can be found here!
  • Note that most studies are observational, non-blinded and have lots of heterogeneity (e.g. different ABX combinations).
  • Also note that these data likely DON’T apply to specific sub-populations at greatly increased risk of resistant organisms (e.g. cystic fibrosis patients).

Jen Babik’s “Fever in the ICU” lectures

Pseudomonas: Paul and Leibovici, CID 2013.(PMID 23580731)


Neurologic prognostication post-arrest

  • We discussed how this is one of the most humbling areas of medicine, as it is incredibly variable and difficult to predict.
  • Thanks so much to Jill Goslinga for digging into the data on the most important neurologic exam findings we and our Neuro colleagues use in our assessment.
  • Two systematic reviews have concluded that two clinical criteria have been found to be 100 percent specific for poor outcome:
    • Absent or extensor motor response on day three
    • Absent pupillary or corneal reflexes on day three
  • A JAMA Rational Clinical Exam review noted 5 clinical signs that strongly predict death or poor neurological outcome:
    • absent corneal reflexes at 24 hours (LR, 12.9; 95% confidence interval [CI], 2.0-68.7),
    • absent pupillary response at 24 hours (LR, 10.2; 95% CI, 1.8-48.6),
    • absent withdrawal response to pain at 24 hours (LR, 4.7; 95% CI, 2.2-9.8),
    • no motor response at 24 hours (LR, 4.9; 95% CI, 1.6-13.0),
    • no motor response at 72 hours (LR, 9.2; 95% CI, 2.1-49.4).
  • Although myoclonic status is associated with poor neurologic outcome, seizures and non-epileptic myoclonus alone are not significant predictors of morbidity or mortality.
    • We often use EEG to evaluate for status for this reason

Neurology. 2006;67(2):203.

Lancet. 1998;352(9143):1808.

JAMA. 2004 Feb 18;291(7):870-9.