Do most patients with mycotic aneurysms have endocarditis?

No! In fact, the great majority of patients who develop mycotic aneurysm (MAs) in the postantibiotic era have no evidence of endocarditis1-3.

MAs are thought to be related to microbial arteritis due to blood stream infection of any source with implantation of circulating pathogen (usually bacterial) in atherosclerotic, diseased, or traumatized aortic intima. Plus, MAs may develop due to an adjacent infectious process (eg, vertebral osteomyelitis), either through direct extension or via lymphatic vessels, pathogen seeding of vasa vasorum, or infection of a pre-existing aneurysm1,2.  All these factors may occur in the absence of endocarditis.

Many of your patients may be at risk of MA such as those with advanced age or history of diagnostic or therapeutic arterial catheterization, illicit intravascular drug use, hemodialysis and depressed host immunity1-3..  Staphylococcus aureus, Salmonella sp, S. epidermidis and Streptococcus sp are common culprits in descending order1-3.

So think of MA in your patient with recent blood stream infection,  particularly due to S. aureus or Salmonella sp, in the setting of persistent signs of infection  with or without evidence of endocarditis.

Final Fun Fact: Did you know that the term “mycotic aneurysm” is a misnomer, having been first introduced by Sir William Osler to describe aneurysms of the aortic arch in a patient with (you guessed it) bacterial not fungal endocarditis?


  1. Gomes MN, Choyke PL, Wallace RB. Infected aortic aneurysms: A changing entity. Ann Surg 1992;215:435-42.
  2. Muller BT, Wegener OR, Grabitz K, et al. Mycotic aneurysms of the thoracic and abdominal aorta and iliac arteries: Experience with anatomic and extra-anatomic repair in 33 cases. J Vasc Surg 2001;33:106-13.
  3. Mukherjee JT, Nautiyal A, Labib SB. Mycotic aneurysms of the ascending aorta. Tex Heart Inst J 2012;39:692-5.
Do most patients with mycotic aneurysms have endocarditis?

Does methotrexate reduce the risk of cardiovascular events in patients with rheumatoid arthritis?

The weight of the evidence suggests that methotrexate reduces the overall risk of cardiovascular events (CVEs)—including myocardial infarction, congestive heart failure, stroke, and or major adverse cardiac events—in RA patients (RR 0.72, 95% CI 0.57-0.91)1.

Aside from its effect on controlling systemic inflammation, methotrexate has also been shown to increase HDL and reduce total cholesterol/HDL ratio in patients with RA compared with treated non-RA controls2. In vitro, methotrexate appears to activate mechanisms involved in reverse transport of cholesterol out of the cell to the circulation for eventual excretion3. Not surprisingly then, methotrexate has also been reported to decrease atherosclerotic plaque burden measured by carotid artery intima-media thickness2.

We tend to think of RA as a disease that primarily causes arthritis but its effects may extend far beyond the joints. Patients with RA have an increased risk of cardiovascular deaths compared to the general population4, likely due to a variety of factors, including accelerated atherosclerosis secondary to chronic inflammation. At baseline, RA patients also have an unfavorable lipid profile with decreased HDL and higher total cholesterol/HDL ratio.

Fun Final Fact: Did you know that methotrexate is on the WHO Model List of Essential Medicines (April 2015) not only as a cancer drug but for treatment of RA as well5?


  1. Roubille C, Richer V, Starnino T, McCourt C, McFarlane A, Fleming P, Siu S, Kraft J, Lynde C, Pope J, Gulliver W, Keeling S, Dutz J, Bessette L, Bissonnette R, Haraoui B. The effects of tumour necrosis factor inhibitors, methotrexate, non-steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis. 2015;74:480-9.
  2. Georgiadis AN, Voulgari PV, Argyropoulou MI, Alamanos Y, Elisaf M, Tselepis AD, Drosos AA. Early treatment reduces the cardiovascular risk factors in newly diagnosed rheumatoid arthritis patients. Semin Arthritis Rheum 2008;38:13-9.
  3. Reiss AB, Carsons SE, Anwar K, Rao S, Edelman SD, Zhang H, Fernandez P, Cronstein BN, Chan ES. Atheroprotective effects of methotrexate on reverse cholesterol transport proteins and foam cell transformation in human THP-1 monocyte/macrophages. Arthritis Rheum 2008;58:3675-83.
  4. Aviña-Zubieta JA, Choi HK, Sadatsafavi M, Etminan M, Esdaile JM, Lacaille D. Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies. Arthritis Rheum 2008; 59:1690-7.
  5. WHO Model List of Essential Medicines (April 2015).


Contributed by Brian Li, Medical Student, Harvard Medical School

Does methotrexate reduce the risk of cardiovascular events in patients with rheumatoid arthritis?

Does hypertension cause epistaxis?

Although traditionally we think of epistaxis as a potential sign of hypertension, particularly when severe, whether hypertension causes epistaxis is unclear and even the association of these 2 conditions has been challenged in recent years.

A 2014 systematic review found that although the majority of studies reported an association between these 2 conditions, many did not include a control group, were of poor methodological quality and did not adjust for confounding variables such as age, sex, and anticoagulation1.  Indeed, a larger study that controlled for many potential confounding factors failed to confirm such an association2.  A small prospective study also found no correlation between the severity of hypertension and epistaxis3.

Even when an association between hypertension and epistaxis has been found, it is unclear how much of the stress of bleeding itself and white coat syndrome may affect the readings1. However, an interesting 2017 study found masked hypertension (normal blood pressure in office, abnormal on ambulatory measurements) in 33.3% of patients with epistaxis with night time blood pressures that were significantly higher among patients with epistaxis4.

So the data is all over the place! It makes sense that long standing hypertension through its effects on blood vessels such as atherosclerosis and endothelium dysfunction may set the stage for epistaxis1,5, particularly in our ever-aging population on anticoagulants.  But whether hypertension by itself is enough to cause epistaxis is likely to be debated for years to come.  



  1. Kikidis D, Tsioufis K, Papanikolaou V, et al. Is epistaxis associated with arterial hypertension? A systematic review of the literature 2014;271:237-243.
  2. Fuchs FD, Moreira LB, Pires CP, et al. Absence of association between hypertension and epistaxis: a population-based study. Blood Press 12:145-48.
  3. Knopfholz J, Lima-Junior E, Précoma-Neto D, et al. Association between epistaxis and hypertension: A one year follow-up after an index episode of nose bleeding in hypertensive patients. Internat J Cardiol 2009;134:e107-e109.
  4. Acar B, Yavuz B, Yildiz E, et al. A possible cause of epistaxis: increased masked hypertension prevalence in patients with epistaxis. Braz J Otorhinolaryngol 2017;83:45-49.
  5. Celik T, Iyisoy A, Yuksel UC, et al. A new evidence of end-organ damage in the patients with arterial hypertension: epistaxis? Internat J Cardiol 2008;141:105-107.
Does hypertension cause epistaxis?

Can I assess the severity of aortic stenosis by physical exam alone?

Even in this age of high-tech medicine, physical exam is still a great starting point for assessing the severity of aortic stenosis (AS) even if you are not a skilled cardiologist like most.

Start out by listening over the right clavicle. If you don’t hear a systolic murmur, you can be pretty confident that your patient doesn’t have moderate to severe AS (>98% sensitivity, LR 0.10)1.

If you hear a systolic murmur look for combination of findings that may increase the likelihood of moderate to severe AS: slow carotid artery upstroke, reduced carotid artery volume, maximal murmur intensity at the second right intercostal space, and reduced intensity of the second heart sound.  The presence of 3 or 4 of these signs increases the likelihood of moderate to severe AS (LR 40), with less than 3 not helping much1.

When considered individually, many of the signs we often attribute to significant AS2 may not be as helpful in part because most of us are not skilled cardiologists and over the years the cause of AS has changed from primarily rheumatic heart disease-related to that advancing age and valve degeneration3.  

So it may not be surprising that murmur intensity (eg grade 3/6 or above) may have a poor sensitivity and is an unreliable predictor of the severity of AS when patients with left ventricular failure are also studied3.  Remember also that the absence of the 2nd sound may not distinguish between moderate and severe AS4



  1. Etchells E, Glenns V, Shadowitz S, et al. A bedside clinical prediction rule for detecting moderate or severe aortic stenosis. J Gen Intern Med 1998;13:699-704.
  2. Etchells EE, Bell C. Robb KV. Does this patient have an abnormal systolic murmur? JAMA 1997;277:564-71.
  3. Das P, Pocock C, Chambers J. The patient with a systolic murmur: severe aortic stenosis may be missed during cardiovascular examination. Q J Med 2000;93:685-8.–jHRtv9AJI2uHlzN79Vzkh~oIrR-rI5mkHle3Yz0R3qIBY0l4P3PssMng~v-IXMNKS~Ghjav8YFTigHN23aEA5yUYllsC7hR25L6h9PA0SZP3QA__&Key-Pair-Id=APKAIUCZBIA4LVPAVW3Q
  4. Aronow WS, Kronzon I. Prevalence and severity of valvular aortic stenosis determined by Doppler echocardiography and its association with echocardiographic and electrocardiographic left  ventricular hypertrophy and physical signs of aortic stenosis in elderly patients. Am J Cardiol 1991;67:776-7.
Can I assess the severity of aortic stenosis by physical exam alone?

Is my patient with aortic stenosis and no atrial fibrillation at higher risk of a cerebrovascular accident?

Several lines of evidence suggests that even in the absence of atrial fibrillation, patients with aortic stenosis (AS) may be at higher risk of a cerebrovascular accident (CVA).

A population-based study from Mayo Clinic examining the risk of cerebrovascular events (primarliy ischemic strokes or transient ischemic attacks) among patients with valvular heart disease reported severe aortic stenosis (study defined as mean pressure gradient >30 mm Hg) as a predictor of cerebrovascular event, independent from atrial fibrillation or age and at rates similar to those of mitral stenosis 1.  Similarly, the simvastatin and ezetimibe in AS study involving patients with mild-to-moderate AS not prescribed oral anticoagulation found that CHA2DS2-VASc was a major predictor of stroke, independent of atrial fibrillation or aortic valve replacement2. Thromboembolic CVA has also been reported in the setting of calcified bicuspid aortic valve with moderate-severe AS3.

Potential factors increasing the risk of CVA in AS include calcium embolization from the valve and increased microthrombus formation on the valve which may be present in 53% of stenotic aortic valves3,4.  In addition, severe AS may be a marker for other conditions that increase risk of CVA, such as atherosclerosis or prothrombotic tendencies1.


  1. Petty GW, Khandheria BK, Whisant JP. Predictors of cerebrovascular event and death among patients with valvular heart disease: A population-based study. Stroke 2000;31:2628-2635.
  2. Greve AM, Dalsgaard M, Bang CN, et al. Stroke in patients with aortic stenosis: The simvastatin and ezetimibe in aortic stenosis study. Stroke 2014;45:1939-1946.
  3. Mahajan N, Khetarpal V, Alfonso L. Stroke secondary to calcific bicuspid aortic valve: Case report and literature review. J Cardiol 2009;54:158-61.
  4. Pleet AB, Massey EW, Vengrow ME. TIA, stroke, and the bicuspid aortic valve. Neurology 1981;31:1540-2. 
Is my patient with aortic stenosis and no atrial fibrillation at higher risk of a cerebrovascular accident?

Where should I expect to hear radiation of mitral regurgitation in my patient with endocarditis?

Mitral regurgitation (MR) murmur can radiate to several places on the chest wall as well as the spine and….ready for this…. the top of the head!

Classically, MR is thought to have 4 patterns of radiation1,2

  1. Axilla and the inferior angle of the left scapula (typical)
  2. Left sternal border, base of the heart and into the neck
  3. Cervical and lumbar spine (down to sacrum)
  4. Right of the sternum (associated with a “giant left atrium”)

Less well-known and perhaps most intriguing is the radiation of MR to the top of the head. Original reports involved patients who often had ruptured chordae tendineae due to subacute bacterial endocarditis and/or rheumatic heart disease2. It was posited that “the flail portion of the mitral valve folds back into the left atrial cavity forming a hood which deflects the regurgitant stream against the atrial wall”.  In the setting of a flail anterior leaflet, if the jet stream is sufficiently high energy and comes in contact with the spine, the murmur may be transmitted by bone conduction to the top of the skull2

I suggest you explain to your patient what you are doing before you auscultate the top of their heads!



  1. Chatterjee K. Physical examination. In Topol EJ, ed. Textbook of cardiovascular medicine, 2007, pp 193-224. Lippincott, Williams &Wilkins. Philadelphia.
  2. Merendino KA, Hessel EA. The “murmur on top of the head” in acquired mitral insufficiency: Pathological and clinical significance. JAMA 1967;199:892-896.
Where should I expect to hear radiation of mitral regurgitation in my patient with endocarditis?

Which is more effective in managing rapid ventricular rate in atrial fibrillation, diltiazem or metoprolol?

Overall, diltiazem may be more effective than metoprolol in the acute management of AFib with RVR without increased side effects based on a few small but randomized double-blind studies.

A systematic review1 based on 2 trials2,3 comparing IV diltiazem with IV metroprolol in patients with atrial fibrillation seen in emergency departments has reported better acute rate control with IV diltiazem (RR 1.8 [95% CI, 1.2-1.6]).  In these studies, the onset of rate control was faster and the percentage decrease in ventricular rate at each time point was higher with IV diltiazem.  In general, 0.25 mg/kg of IV diltiazem (max 25 mg) and 0.15 mg/kg of IV metoprolol (max 10 mg) were used.

Exclusion criteria in these studies included severe congestive heart failure, hypotension, acute coronary syndrome, and use of either class of drugs within the past five days.


  1. Martindale JL, deSouza IS, Silverberg M et al.. Beta-blockers versus calcium channel blockers for acute rate control of atrial fibrillation with rapid ventricular response: a systematic review. Eur J Emerg Med 2015;22: 150-154.
  2. Demircan C, Cikriklar H, Engindeniz Z, et al. Comparison of the effectiveness of intravenous diltiazem and metoprolol in the management of rapid ventricular rate in atrial fibrillation. Emerg Med J 2005;22: 411-414. 
  3. Fromm C, Suan SJ, Cohen V, et al. Diltizem vs metoprolol in the management of atrial fibrillation or flutter with rapid ventricular rate in the emergency department. J Emerg Med 2015;49:175-82.

Contributed by William L. Hwang, MD, Mass General Hospital, Boston, MA.

Which is more effective in managing rapid ventricular rate in atrial fibrillation, diltiazem or metoprolol?