Kokko Conference: Do protease inhibitors lead to improved outcomes in AL cardiac amyloidosis?

The Bottom Line: . In a study of diflunisal in ATTR cardiac amyloidosis (both mutant and wt), stable mean left ventricular (LV) mass, LVEF and cardiac biomarkers were seen during the course of therapy.  Nephrotoxicity and volume overload was observed as AEs. A RCT of diflunisal for familial amyloid polyneuropathy (FAP; caused by mutant ATTR) reported neurological stability at 2 years in 29.7 % of patients in the diflunisal arm versus 9.4 % of the placebo arm.  Tafamidis, a kinetic stabilizer of TTR protein, is active in FAP and leads to a delay in peripheral neurologic impairment, with minimal AEs.  A phase 2 study of tafamidis in ATTR amyloid cardiomyopathy showed TTR stabilization in
97 % of wt patients with mild to moderate CHF.

References:  Chakraborty R. et al.  Newer Therapies for Amyloid Cardiomyopathy.  Curr Heart Fail Rep.  2016 Oct;13(5):237-246.

Summary: OLT remains the benchmark for treatment of ATTR amyloidosis; however, progression of cardiac amyloidosis after OLT due to an increase in the wild:mutant TTR ratio is concerning. Development of BTTR stabilizers is a promising arena in hereditary amyloidosis and further studies are needed to ascertain survival benefit in those with cardiac involvement.

Posted in Grady, Therapy

EUHM Resident Report: Prevalence of Chagas disease in the United States.

The Bottom Line: In the United States, little evidence is available to document Chagas disease prevalence, assess congenital and vector-borne transmission risk, and quantify the clinical disease burden. Based on immigration estimates for the United States and prevalence estimates in Latin America, more than 300,000 persons with Chagas disease are living in this country; many of these persons do not know that they are infected. An estimated 63–315 babies acquire T. cruzi infection congenitally in the United States every year but most infections go undetected and untreated. Based on these estimates, chagasic cardiomyopathy, which can be prevented through early treatment, affects approximately 30,000–45,000 persons in the United States.

Montgomery, S. P., Starr, M. C., Cantey, P. T., Edwards, M. S., & Meymandi, S. K. (2014). Neglected Parasitic Infections in the United States: Chagas Disease. The American Journal of Tropical Medicine and Hygiene, 90(5), 814–818.

Although an estimated 300,000 persons with Chagas disease live in the United States, little is known about the burden of chagasic heart disease. It is not known how often congenital or vector-borne transmission of T. cruzi occurs in the United States, although it is known that infected mothers and infected vector bugs are found in this country

Posted in EUHMidtown | Tagged

EUH Morning Report: Does my patient have hepatomegaly?

The Bottom Line: Hepatomegaly should be considered for patients with known or suspected liver disorders, malignancy, or congestive heart failure. When there is a suspicion of liver disease, it’s recommended that clinicians forgo the scratch test and use percussion to estimate the liver span (>12 cm = abnormal). Liver ultrasonography can be used to confirm the clinical findings when indicated (Simel and D’silva, 2009). Tucker et al (1997) found the scratch test to be neither a valid nor reliable method of physical exam.

References: Simel DL, D’silva M. Hepatomegaly. In The Rational Clinical Examination: Evidence-Based Clinical Diagnosis. New York, NY: McGraw-Hill, 2009.

Tucker WN, Saab S, Rickman LS, Mathews WC. The scratch test is unreliable for detecting the liver edge. J Clin Gastroenterol. 1997 Sept;25(2):410-4.

Summary: The probability that the liver edge can be felt below the right costal margin is about 50% (Simel and D’silva, 2009). Palpating a liver edge below the right costal margin correlates poorly with the actual liver span, although it does increase the likelihood that the patient will have an enlarged liver. The failure to identify the liver edge does not rule out the presence of an increased liver span.

Although the clinical estimation of liver span is reported to be more accurate with enlarged livers, the results of Tucker et al’s (1997) illustrate that the estimation of liver span by the scratch test is inaccurate and imprecise regardless of liver span. In this prospective, double-blind study of 22 patients and multiple examiners comparing the scratch test to ultrasound, they also found the scratch test to be imprecise in estimating the lower boundary of the liver (Tucker et al, 1997).

An updated literature search concluded that “clinicians should stop assessing the liver span by ‘scratching’ the abdomen.” (Simel and D’silva, 2009).

Posted in Diagnosis, EUH

EUH Dressler Conference: What are standard treatments and NSAIDS for pericarditis?

The Bottom Line:  Aspirin or non-steroidal anti-inflammatory drugs are standard first-line therapy for acute pericarditis.

Acute pericarditis (for complete information, see DynaMed Plus):

  • ibuprofen 600 mg every 8 hours for 1-2 weeks, then taper by 200-440 mg every 1-2 weeks until resolution of symptoms and improvement of acute inflammatory markers
  • aspirin 750-1,000 mg orally every 8 hours for 1-2 weeks, then taper by 250-500 mg every 1-2 weeks until resolution of symptoms and improvement of acute inflammatory markers (preferred if other indication for antiplatelet therapy)
  • give colchicine as first-line therapy for acute pericarditis as adjunct to aspirin/NSAID (ESC Class I, Level A)
  • typical colchicine dosing for acute pericarditis
    • 0.5-0.6 mg once daily for 3 months for patients < 70 kg
    • 0.5-0.6 mg twice daily for 3 months for patients ≥ 70 kg
    • available tablets in United States (Colcrys) are 0.6 mg instead of 0.5 mg

Recurrent pericarditis (for complete information, see DynaMed Plus):

  • give aspirin or NSAIDs at full doses (if tolerated) until complete resolution of symptoms (ESC Class I, Level A)
  • if ischemic heart disease is a concern or antiplatelet therapy is required, aspirin should be considered at medium doses (1-2.4 g/day) (ESC Class IIa, Level C)
  • NSAIDs contraindicated in patients with pericarditis complicating acute myocardial infarction (aspirin preferred with addition of colchicine if unresponsive to high-dose aspirin)
  • aspirin 500-1,000 mg every 6-8 hours (range 1.5-4 g/day) for weeks-months, then taper by 250-500 mg every 1-2 weeks
  • ibuprofen 600 mg every 8 hours (range 1,200-2,400 mg/day) for weeks-months, then taper by 200-400 mg every 1-2 weeks
  • give colchicine 0.5 mg twice daily (or 0.5 mg daily for patients < 70 kg or intolerant to higher doses) for 6 months as adjunct to aspirin/NSAIDs
  • continuation of colchicine for > 6 months should be considered in select patients to improve response to medication and remission rates and prevent recurrences

References: Bach RG. ACP Journal Club. Colchicine reduced further recurrence after a first recurrence of pericarditis. Ann Intern Med. 2012 Feb 21;156(4):JC2-04. doi:10.7362/0003-4819-156-4-201202210-02004.

DynaMed Plus [Internet]. Ipswich (MA): EBSCO Information Services. 1995 – . Record No. 115401, Acute and recurrent pericarditis/Treatment/Medications/Nonsteroidal anti-inflammatory drugs (NSAIDS); [updated 2017 Sep 26, cited 2017 Oct 12]; [about 19 screens]. University login required.

Imazio M, Brucato A, Cemin R, Ferrua S, et al. A randomized trial of colchicine for acute pericarditis. N Engl J Med. 2013 Oct 17;369(16):1522-8. doi:10.1056/NEJMoa1208536.

Summary: Because recurrence may imply a lack of sustained benefit from non-steroidal anti-inflammatory drugs, clinicians often prescribe corticosteroids, a common practice supported by limited observational data. Corticosteroid use in pericarditis, however, is associated with an increased risk for recurrence and side effects (Bach, 2012).

The CORP trial is the first multicenter, blinded, randomized, placebo-controlled trial to test the efficacy and safety of colchicine for recurrent pericarditis. Recurrence at 18 months and persistence of symptoms at 72 hours were reduced by > 50% compared with placebo. Notably, colchicine was well tolerated at the doses used, with no severe side effects, and drug withdrawal rates were similar to placebo.

In a separate randomized control trial, Imazio et al (2013) found that colchicine reduced the rate of symptom persistence at 72 hours (19.2% vs. 40.0%, P = 0.001), the number of recurrences per patient (0.21 vs. 0.52, P = 0.001), and the hospitalization rate (5.0% vs. 14.2%, P = 0.02). Colchicine also improved the remission rate at 1 week (85.0% vs. 58.3%, P<0.001).

Given the increased risk for recurrence and side effects with corticosteroids (2), colchicine should be strongly endorsed as first-line treatment for recurrent pericarditis (Bach, 2012).

Posted in Applying evidence, EUH, Therapy

EUH Dressler Conference: What is the clinical exam for pericardial tamponade?

The Bottom Line: Among patients with cardiac tamponade, a minority will not have dyspnea, tachycardia, elevated jugular venous pressure, or cardiomegaly on chest radiograph. A pulsus paradoxus greater than 10 mm Hg among patients with a pericardial effusion helps distinguish those with cardiac tamponade from those without.

Reference: Roy CL, Minor MA, Brookhart MA, Choudhry NK. Does this patient with a pericardial effusion have cardiac tamponade? JAMA. 2007 Apr 25;297(16):1810-8.

Summary: Signs: Depending on the degree of hemodynamic compromise, vital signs may reveal tachycardia, hypotenstion, and tachypnea. The classic findings of tamponade were described in 1935 and are known as the Beck triad: decreasing arterial, blood pressure, increasing jugular venous pressure, and a small, quiet heart. This is seen in surgical patients; medical patients, who generally develop pericardial effusions slowly, may not exhibit any of the Beck triad findings.

Symptoms: The important symptoms include dyspnea, chest pain, or fullness. Nausea or abdominal pain from hepatic and visceral congestion or dysphagia from esophageal compression may be reported. Nonspecific symptoms such as lethargy, fever, cough, weakness, fatigue, anorexia, and palpitations also occur.

Pulsus paradoxus: Most textbooks define it as a greater than 10-mm Hg difference between initial detection of sounds on expirations and the constant presence of sounds with each heartbeat. It can be detected by palpating the radial pulse and noting an inspiratory diminution of the pulse during normal respirations, or by observing the inspiratory diminution of the peripheral pulse on an arterial catheter tracing or pulse oximeter.

Other signs: Some patients with tamponade have a pericardial rub. Patients with cardiac tamponade often have an elevated jugular venous pressure at bedside examination, but the sensitivity of this finding may be reduced by the patient’s body habitus and, theoretically, in the setting of hypovolemia.

Electrocardiogram and chest radiograph: Electrocardiogram findings indicating a large pericardial effusion include low QRS voltage, electrical alternans, atrial arrhythmias, and, if pericardial inflammation is present, ST-segment elevation and PR-segment depression. Depending on the size of the effusion, the chest radiography may be normal or may demonstrate an enlarged, globular cardiac silhouette and/or and epicardial fat stripe or “double lucency” sign on lateral views.

Posted in Diagnosis, EUH

EUH Morning Report: Delayed paracentesis and mortality risk with spontaneous bacterial peritonitis

The Bottom Line: In a study of hospitalized patients with spontaneous bacterial peritonitis (SBP), Kim et al (2014) concluded:

  • Patients who receive delayed paracentesis (DP) had a higher in-hospital mortality (27% vs 13%) compared with those who received early paracentesis (EP).
  • Patients who received DP had longer intensive care stays, hospital days, and higher 3-month mortality.
  • DP was associated with a 2.7-fold increase in in-hospital mortality, after adjusting for presenting MELD score and creatinine levels.
  • Each hour delay in the performance of paracentesis from hospitalization was associated with 3.3% increase in in-hospital mortality.
  • Paracentesis performed early on presentation in patients with cirrhosis and ascites may improve short-term survival.

Reference: Kim JJ, Tsukamoto MM, Mathur AK, Ghomri YM, et al. Delayed paracentesis is associated with increased in-hospital mortality in patients with spontaneous bacterial peritonitis. Am J Gastroenterol. 2014 Sep;109(9):1436-42. doi:10.1038/ajg.2014.212.

Summary: Early diagnosis via paracentesis is critical to the successful treatment of patients with SBP. EP is defined as receiving paracentesis < 12h and DP 12-72h from hospitalization.







(Kim et al, 2014, p.1439)

Patients with cirrhosis frequently develop life-threatening bacterial infections, and SBP is one of the most frequent sources of sepsis in patients with decompensated liver disease. Early detection and initiation of antimicrobial therapy are critical to successful treatment of SBP. Guidelines recommend diagnostic paracentesis in any patient with cirrhosis and ascites admitted to the hospital, presenting with signs and symptoms, or worsening renal and hepatic dysfunction.

Posted in Diagnosis, EUH, Therapy

EUH Morning Report: Diagnosing ascites

The Bottom Line: Three guidelines are most useful when determining if a patient has ascites (Williams and Simel, 1992, p.2648):

  1. The most useful findings for ruling out ascites are negative histories of ankle swelling or increased abdominal girth, and the inability  to demonstrate bulging flanks, flank dullness, or shifting dullness.
  2. The most powerful findings for making the diagnosis of ascites are a positive fluid wave, shifting dullness, or peripheral edema.
  3. The puddle sign is difficult to perform and uncomfortable for patients and is not sensitive to small amounts of ascites. It should not be performed.

Reference: Williams JW Jr, Simel DL. The rational clinical examination. Does this patient have ascites? How to divine fluid in the abdomen. JAMA. 1992 May 20;267(19):2645-2648.

Summary: Free fluid in the abdominal cavity is ascites. When clinically detectable, ascites may indicate underlying heart failure, liver disease, nephrotic syndrome, or malignancy. Williams and Simel (1992) use three clinical examples to illustrate how to diagnose ascites in the clinical exam and why it’s important:

  • Eliciting the symptoms and signs of acites.
    • Patient history: Examiner should ask about recent ankle edema, weight gain, or change in abdmoinal girth, as well as a history of liver disease or congestive heart failure.
    • Physical exam: Inspection for bulging flanks, percussion for flank dullness, a test for shifting dullness, and a test for a fluid wave.
  • Accuracy of history and symptoms for ascites.
    • The clinical history distinguishes patients with high and low probabilities for ascites. Ascites is unlikely when patients report no increase in abdominal girth, and it’s very unlikely in male patients who report no history of recent ankle swelling.
  • Accuracy of signs for ascites.
    • The finding of a fluid wave, shifting dullness, or peripheral edema increased the likelihood of ascites the most.
    • The absence of bulging flanks, flank dullness, shifting dullness, or peripheral edema decreased the likelihood of ascites the most.

best ascites picture



Posted in Diagnosis, EUH