Cardiac disease

Chest CT scan of my patient with congestive heart failure (CHF) and shortness of breath shows mediastinal adenopathy.  Can mediastinal adenopathy be caused by CHF alone?

FA Manian MD, MPH, , , , , , Leave a comment

Yes! Mediastinal adenopathy (commonly defined as 1 or more lymph nodes with a short axis diameter >1 cm) may be caused by CHF alone (AKA “congestive adenopathy”). 1-4

Although not as common as alveolar/interstitial edema on chest CT scan, hypertrophy of mediastinal lymph nodes may occur in a significant number of patients with CHF.  In a study involving 215 patients with CHF and no confounding etiology of adenopathy, 68% had evidence of adenopathy, particularly involving the right paratracheal and precarinal, subcarinal and other mediastinal lymph nodes; hilar and single station adenopathy were less common. The findings of pulmonary edema on CT and pleural effusion were significantly associated with adenopathy.1

In a study involving 3 patients with mediastinal adenopathy and CHF, lymph node biopsy showed noninflammatory, benign lesions that did not affect the node structure. Follow-up CT scan in 2 patients at 8 and 10 months showed no changes in the morphologic characteristics of mediastinal lymph nodes, while in another patient most of the enlarged lymph nodes disappeared at 5 months post- acute phase of the CHF.2   Interestingly, another study involving 31 cases of “subacute left heart failure” found that average ejection fraction was lower among patients with adenopathy (34% vs 43%).3

One potential mechanism for CHF-related adenopathy is that the excess lung fluid causes increased flow of fluid through the lymphatic channels and into the lymph nodes resulting in their congestion and enlargement.1

 

Bonus Pearl: Did you know that experimental animal studies have shown that acute CHF is associated with significant increases in mediastinal lymphatic flow and lymphatic vessel dilatation? 4-5

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Shweihat YR, Perry J, Etman Y, et al. Congestive adenopathy: A mediastinal sequela of volume overload. J Bronchol Intervent Pulmonol 2016; 23:298-302. https://pubmed.ncbi.nlm.nih.gov/27623420/
  2. Ngom A, Dumont P, Diot P, et al. Benign mediastinal lymphadenopathy in congestive heart failure. CHEST 2001;119: 653-656. https://pubmed.ncbi.nlm.nih.gov/11171755/
  3. Chabbert V, Canevet G, Baixas C, et al. Mediastinal lymphadenopathy in congestive heart failure: a sequential CT evaluation with clinical and echocardiographic correlations. Eur Radiol 2004;14:881-889. https://pubmed.ncbi.nlm.nih.gov/14689226/
  4. Drake RE, Dhother S, Teague RA, et al. Lymph flow in sheep with rapid cardiac ventricular pacing. Am J Physiol 1997; 272:1595-1598. https://pubmed.ncbi.nlm.nih.gov/9176352/
  5. Leeds SE, Uhley HN, Telesky LB. Direct cannulation and injection lymphangiography of the canine cardiac and pulmonary efferent mediastinal lymphatics in congestive hart failure. Invest Radiol 1981;16:193-200. https://pubmed.ncbi.nlm.nih.gov/6266975/

Disclosures/Disclaimers: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

Chest CT scan of my patient with congestive heart failure (CHF) and shortness of breath shows mediastinal adenopathy.  Can mediastinal adenopathy be caused by CHF alone?

Should I consider treating my patient with heart failure with an SGLT2 inhibitor?

FA Manian MD, MPH, , , , , , , , , , , , , , 1 Comment

Absolutely! Although sodium glucose cotransporter 2 (SGLT2) inhibitors are often used for their antidiabetic properties, more recently they have been shown to have extraordinary benefits in patients with heart failure.

 In 2015, a large randomized controlled trial, EMPA-REG OUTCOME, showed that empagliflozin significantly lowered overall death, death from cardiovascular events, and hospitalizations for heart failure in patients who had type II diabetes (T2DM) and cardiovascular disease1.

Later, 2 other randomized controlled trials showed that patients with heart failure with reduced ejection fractions (HFrEF), irrespective of a diagnosis of T2DM, had lower rates of death from cardiovascular causes and better heart failure outcomes when treated with SGLT2 inhibitors2,3.

In 2021, the EMPEROR Preserved trial showed that SGLT2 inhibitors provide significant clinical benefit for patients with heart failure with preserved ejection fraction (HFpEF), irrespective of the presence of T2DM4. In addition, multiple studies have shown substantial benefit to starting SGLT2 inhibitors during or shortly after a hospitalization for heart failure.5,6,7

 The effectiveness of SGLT2 inhibitors in heart failure is also reflected in the updated guidelines from the American College of Cardiology/American Heart Association8  that recommend  use of SGLT2 inhibitors in patients with chronic symptomatic HFrEF.  In addition,  the guidelines state that SGLT2 inhibitors can be beneficial in decreasing heart failure hospitalizations and cardiovascular mortality for patients mildly reduced ejection fraction and those with HFpEF.

 Potential mechanisms of action of SGLT2 inhibitors in heart failure include reduction in myocardial oxidative stress, decrease cardiac preload and afterload, increase endothelial function, decrease arterial stiffness, and increase muscle free fatty acid uptake which leads to increased availability of ketones during times of stress.9 

So the data to date suggest that we should consider SGLT2 inhibitors as part of our armamentarium for treatment of heart failure unless, of course, there are contraindications, including pregnancy/risk of pregnancy, breastfeeding, eGFR <30mL/min/1.73 m2, symptoms of hypotension, systolic blood pressure <95mmHg, or a known allergic/other adverse reactions. 10

Bonus Pearl: Did you know that SGLT 2 inhibitors are derived from phlorizin, a naturally occurring phenol glycoside first isolated back in 1835 from the bark of apple tree in 1835? 11

Contributed by Yisrael Wallach, MD, St. Louis, Missouri

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Zinman, B., Wanner, C., Lachin, J. M., Fitchett, D., Bluhmki, E., Hantel, S., … & Inzucchi, S. E. (2015). Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. New England Journal of Medicine, 373(22), 2117-2128. https://pubmed.ncbi.nlm.nih.gov/26378978/
  2. McMurray, J. J., Solomon, S. D., Inzucchi, S. E., Køber, L., Kosiborod, M. N., Martinez, F. A., … & Langkilde, A. M. (2019). Dapagliflozin in patients with heart failure and reduced ejection fraction. New England Journal of Medicine, 381(21), 1995-2008. https://pubmed.ncbi.nlm.nih.gov/31535829/
  3. Packer, M., Anker, S. D., Butler, J., Filippatos, G., Pocock, S. J., Carson, P., … & Zannad, F. (2020). Cardiovascular and renal outcomes with empagliflozin in heart failure. New England Journal of Medicine, 383(15), 1413-1424. https://pubmed.ncbi.nlm.nih.gov/32865377/
  4. Anker, S. D., Butler, J., Filippatos, G., Ferreira, J. P., Bocchi, E., Böhm, M., … & Packer, M. (2021). Empagliflozin in heart failure with a preserved ejection fraction. New England Journal of Medicine, 385(16), 1451-1461. https://pubmed.ncbi.nlm.nih.gov/34449189/
  5. Cunningham, J. W., Vaduganathan, M., Claggett, B. L., Kulac, I. J., Desai, A. S., Jhund, P. S., … & Solomon, S. D. (2022). Dapagliflozin in Patients Recently Hospitalized With Heart Failure and Mildly Reduced or Preserved Ejection Fraction. Journal of the American College of Cardiology. https://pubmed.ncbi.nlm.nih.gov/36041912/
  6. Voors, A. A., Angermann, C. E., Teerlink, J. R., Collins, S. P., Kosiborod, M., Biegus, J., … & Ponikowski, P. (2022). The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure: a multinational randomized trial. Nature medicine, 28(3), 568-574. https://pubmed.ncbi.nlm.nih.gov/35228754/
  7. Bhatt, D. L., Szarek, M., Steg, P. G., Cannon, C. P., Leiter, L. A., McGuire, D. K., … & Pitt, B. (2021). Sotagliflozin in patients with diabetes and recent worsening heart failure. New England Journal of Medicine, 384(2), 117-128. https://pubmed.ncbi.nlm.nih.gov/33200892/
  8. Heidenreich, P. A., Bozkurt, B., Aguilar, D., Allen, L. A., Byun, J. J., Colvin, M. M., … & Yancy, C. W. (2022). 2022 AHA/ACC/HFSA guideline for the management of heart failure: Executive summary: a report of the American College of Cardiology/American heart association joint Committee on clinical practice guidelines. Journal of the American College of Cardiology, 79(17), 1757-1780. https://pubmed.ncbi.nlm.nih.gov/35379504/
  9. Muscoli, S., Barillà, F., Tajmir, R., Meloni, M., Della Morte, D., Bellia, A., … & Andreadi, A. (2022). The New Role of SGLT2 Inhibitors in the Management of Heart Failure: Current Evidence and Future Perspective. Pharmaceutics, 14(8), 1730. https://pubmed.ncbi.nlm.nih.gov/36015359/
  10. Aktaa, S., Abdin, A., Arbelo, E., Burri, H., Vernooy, K., Blomström-Lundqvist, C., … & Gale, C. P. (2022). European Society of Cardiology Quality Indicators for the care and outcomes of cardiac pacing: developed by the Working Group for Cardiac Pacing Quality Indicators in collaboration with the European Heart Rhythm Association of the European Society of Cardiology. EP Europace, 24(1), 165-172. https://pubmed.ncbi.nlm.nih.gov/34455442/
  11. Petersen, C. (1835). Analyse des phloridzins. Annalen der pharmacie, 15(2), 178-178. 

Disclosures: The listed questions and answers are solely the responsibility of the author and do not necessarily represent the official views of Mercy Hospital-St. Louis, Massachusetts General Hospital, Harvard Catalyst, Harvard University, their affiliate academic healthcare centers, or its contributors. Although every effort has been made to provide accurate information, the author is far from being perfect. The reader is urged to verify the content of the material with other sources as deemed appropriate and exercise clinical judgment in the interpretation and application of the information provided herein. No responsibility for an adverse outcome or guarantees for a favorable clinical result is assumed by the author. Thank you!

 

 

Should I consider treating my patient with heart failure with an SGLT2 inhibitor?

Is there a connection between my patient’s blood type and risk of thromboembolic events?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

The weight of the evidence to date seem to suggest that non-blood group O may be associated with non-valvular atrial fibrillation (NVAF)-related peripheral cardioembolic complications, myocardial infarction (MI) and ischemic stroke. 1-4

A 2015 retrospective Mayo Clinic study involving patients with NVAF adjusted for CHADS2 score found significantly lower rate of peripheral embolization in those with blood group O compared to those with other blood groups combined (3% vs 2%, O.R. 0.66, 95% CI, 0.5-0.8); rates of cerebral thromboembolic events were not significantly different between the 2 groups, however. 1

A 2008 systematic review and meta-analysis of studies spanning over 45 years reported a significant association between non-O blood group and MI, peripheral vascular disease, cerebral ischemia of arterial origin, and venous thromboembolism.2 Interestingly, the association was not significant for angina pectoris or for MI when only prospective studies were included.  Some studies have reported that the association between von Willebrand factor (VWF) and the risk of cardiovascular mortality may be independent of blood group. 5,6

Although the apparent lower risk of thromboembolic conditions in O blood group patients may be due to lower levels of VWF and factor VIII in this population 1,4, other pathways likely  play a role.7  

As for why the rate of peripheral (but not cerebral) thromboembolic events in NVAF is affected by blood group, one explanation is that because of their size, larger clots (facilitated by lower VWF levels) may bypass the carotid and vertebral orifices in favor of their continuation downstream to the “peripheral bed”.1

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References

  1. Blustin JM, McBane RD, Mazur M, et al. The association between thromboembolic complications and blood group in patients with atrial fibrillation. Mayo Clin Proc 2015;90;216-23. https://www.sciencedirect.com/science/article/abs/pii/S002561961401043X
  2. Wu O, Bayoumi N, Vickers MA, et al. ABO (H) groups and vascular disease: a systematic review and meta-analysis. J Thromb Haemostasis 2008;6:62-9. https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1538-7836.2007.02818.x
  3. Medalie JH, Levene C, Papier C, et al. Blood groups, myocardial infarction, and angina pectoris among 10,000 adult males. N Engl J Med 1971;285:1348-53. https://www.nejm.org/doi/pdf/10.1056/NEJM197112092852404
  4. Franchini M, Capra F, Targher G, et al. Relationship between ABO blood group and von Willebrand factor levels: from biology to clinical implications. Thrombosis Journal 2007, 5:14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2042969/
  5. Meade TW, Cooper JA, Stirling Y, et al. Factor VIII, ABO blood group and the incidence of ischaemic heart disease. Br J Haematol 1994;88:601-7. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2141.1994.tb05079.x
  6. Jager A, van Hinsbergh VW, Kostense PJ, et al. von Willebrand factor, C-reactive protein, and 5-year mortality in diabetic and nondiabetic subjects: the Hoorn Study. Arterioscl Thromb Vasc Biol 1999;19:3071-78. https://www.researchgate.net/publication/12709043_von_Willebrand_Factor_C-Reactive_Protein_and_5-Year_Mortality_in_Diabetic_and_Nondiabetic_Subjects_The_Hoorn_Study
  7. Sode BF, Allin KH, Dahl M, et al. Risk of venous thromboembolism and myocardial infarction associated with factor V Leiden and prothrombin mutations and blood type. CMAJ 2013.DOI:10.1503/cmaj.121636. https://www.ncbi.nlm.nih.gov/pubmed/23382263
Is there a connection between my patient’s blood type and risk of thromboembolic events?

My patient with inferior myocardial infarction with Q-waves 2 years ago now has no evidence of Q waves on his EKG. Can Q-waves from myocardial infarction really regress over time?

FA Manian MD, MPH, , , Leave a comment

Short answer: Yes! Q-waves may regress following transmural myocardial infarction (ATMI) and in fact this phenomenon may not be as unusual as once thought, occurring in 7-15% of patients (1,2).

 
A prospective study involving patients with ATMI evaluated by coronary angiography and followed for an average of 65 months found an 11% rate of loss of Q-waves over an average of 14 months after ATMI. Factors associated with loss of Q-waves included lower peak creatine kinase values, lower left ventricular end-diastolic pressures, higher ejection fractions, fewer ventricular aneurysms and lower rate of congestive heart failure, all leading to the authors’ conclusion that Q-wave loss may be related to a smaller infarct size (1).

 
Similar findings were reported from patients enrolled in the Aspirin Myocardial Infarction Study with a loss of a previously documented diagnostic Q-wave confirmed in 14.2% of participants over an average of 38 months. Mortality among patients who lost Q-waves was not significantly different than among those with persistent Q-waves in a single infarct location (2).

 
These observations suggest that Q-waves in the setting of ATMI may not necessarily be pathognomonic of myocardial necrosis and, at least in some instances, may be due to tissue ischemia, edema and inflammation causing reversible myocardial and electrical stunning (3). Of interest, reversible Q-waves have also been reported in acute myocarditis (4).

Bonus Pearl: Did you know that the EKG waves P and Q were likely named by Einthoven, the inventor of EKG, after the designation of the same letters by Descartes, the father of analytical geometry, in describing refraction points? (5). 

 

If you liked this post, sign up under MENU and catch future fresh pearls straight into your mailbox!

 

 

References
1. Coll S, Betriu A, De Flores T, et al. Significance of Q-wave regression after transmural acute myocardial infarction. Am J Cardiol 1988;61:739-42.
2. Wasserman AG, Bren GB, Ross AM, et al. Prognostic implications of diagnostic Q waves after myocardial infarction. Circulation 1982;65:1451-55.
3. Barold SS, Falkoff MD, Ong LS, et al. Significance of transient electrocardiographic Q waves in coronary artery disease. Cardiol Clin 1987;5:367-80.
4. Dalzell JR, Jackson CE, Gardner RS. Masquerade: Fulminant viral myocarditis mimicking a Q-wave anterolateral myocardial infarction. Am J Med 2009. Doi:10.1016/j.amjmed.2009.01.015.

5. Hurst, JW.  Naming of the waves in the ECG, with a brief account of their genesis. Circulation 1998;98:1937-42. 

 

My patient with inferior myocardial infarction with Q-waves 2 years ago now has no evidence of Q waves on his EKG. Can Q-waves from myocardial infarction really regress over time?

Why is the bicuspid aortic valve of my middle age patient with endocarditis so heavily calcified?

FA Manian MD, MPH, , , , Leave a comment

Congenital bicuspid aortic valve (BAV) is a significant risk factor for valvular calcification, occurring about 20 years earlier than people with normal tricuspid aortic valve as they age. In fact, despite its prevalence of only 1-2% in the population, BAV may account for 50% of aortic valve stenosis (1).

 
Two potential mechanisms could account for the propensity of patients with BAV to develop valve calcification. First, genetic mutations that  account for some of the cases of BAV disease, may also be associated with valvular calcification (1). NOTCH1 mutation is one such candidate causing early developmental defect in the aortic valve, while later causing de-repression of calcium deposition (2). A mutation of the gene for endothelial nitric oxide synthase (eNOS) involved in preventing calcification in animal and tissue experiments may be another factor (3,4).

 
Besides genetic explanations, alteration in the mechanical force environments of the BAV itself likely plays an important part in the premature degeneration and calcification of the valve (1). Stenotic and skewed forward flow along with increased jet velocity may increase shear forces on the valve. The resultant inflammatory response and apoptosis could lead to a diseased valve, not unlike what may be seen with tricuspid aortic valve under similar circumstances (5).

 

Perhaps more fascinating is the observation that fluid shear itself may influence bone morphogenetic protein expression, further contributing to valvular calcification (6).

Bonus Pearl: Did you know that the risk of infective endocarditis may be much higher (>20-fold) among patients with BAV compared to those with triscuspid aortic valve (7)?

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

 

References
1. Yap CH, Saikrishanan N, Tamilselvan G, et al. The congenital bicuspid aortic valve can experience high-frequency unsteady shear stresses on its leaflet surface. Am J Physiol Heart Circ Physiol 2012; 303:H721-H731. doi:10.1152/ajpheart.00829.2011. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3468455/
2. Nigam V, Srivastava D. Notch 1 represses osteogenic pathways in aortic valve cells. J Mol Cell Cardiol 2009;47:828-34. https://www.ncbi.nlm.nih.gov/pubmed/19695258
3. Rajamannan NM, Subramanian M, Stock SR, et al. Atorvastatin inhibits calcification and enhances nitric oxide synthase production in the hypercholesterolaemic aortic valve disease. Heart 2005;91:806-10. https://www.ncbi.nlm.nih.gov/pubmed/15894785
4. Kennedy JA, Hua X, Mishra K, et al. Inhibition of calcifying nodule formation in cultured porcine aortic valve cells by nitric oxide donors. Eur J Pharmacol 2009;602:28-35. https://www.ncbi.nlm.nih.gov/pubmed/19056377
5. Wallby L, Janerot-Sjöberg B, Steffensen T, Broqvist M. T lymphocyte infiltration in non-rheumatic aortic stenosis: a comparative descriptive study between tricuspid and bicuspid aortic valves. Heart 88: 348–351, 2002. https://www.ncbi.nlm.nih.gov/pubmed/12231589
6. Sorescu GP, Song H, Tressel SL, et al. Bone morphogenic protein 4 produced in endothelial cells by oscillatory shear stress induces monocyte adhesion by stimulating reactive oxygen species production from a nox1-based NADPH oxidase. Circ Res 2004;84:773-79. https://www.ncbi.nlm.nih.gov/pubmed/15388638
7. Kiyota Y, Corte AD, Vieira VM, et al. Risk and outcomes of aortic valve endocarditis among patients with bicuspid and tricuspid aortic valves. Open Heart J 2017;4:e000545. Doi:10.1136/opnhrt-2016-000545. https://openheart.bmj.com/content/openhrt/4/1/openhrt-2016-000545.full.pdf

Why is the bicuspid aortic valve of my middle age patient with endocarditis so heavily calcified?

My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Yes! Arterial thromboembolism—just as venous thromboembolism— is more common in patients with cancer.

In a large 2017 epidemiologic study involving patients 66 years of age or older, the 6-month cumulative incidence of MI was nearly 3-fold higher in newly-diagnosed cancer patients compared to controls, with the excess risk resolving by 1 year. 1 These findings were similar to a previous report involving patients with newly-diagnosed cancer, although in that study the overall coronary heart disease risk remained slightly elevated even after 10 years. 2

In addition, the incidence of coronary events and unstable ischemic heart disease during the 2 year period prior to the diagnosis of cancer is 2-fold higher among cancer patients suggesting that ischemic heart disease may be precipitated by occult cancer. 3

The association of cancer and thromboembolic coronary events may be explained through several mechanisms, including development of a prothrombotic or hypercoagulable state through acute phase reactants, abnormal fibrinolytic activity and increased activation of platelets which are also significantly involved in the pathophysiology of acute coronary syndrome (ACS). 4 Coronary artery embolism from cancer-related marantic endocarditis may also occur.5

More specific to our case, primary brain tumors may be associated with a hypercoagulable state through expression of potent procoagulants such as tissue factor and tissue factor containing microparticles, with a subset producing carbon monoxide, another procoagulant. 6

So our patient’s MI prior to his surgery for brain tumor diagnosis might have been more than a pure coincidence!

Bonus Pearl: Did you know that cancer-related prothrombotic state, also known as  “Trousseau’s syndrome” was first described in 1865 by Armand Trousseau, a French physician who diagnosed the same in himself and died of gastric cancer with thrombotic complications just 2 years later? 7,8

References

  1. Navi BB, Reinder AS, Kamel H, et al. Risk of arterial thromboembolism in patients with cancer. JACC 2017;70:926-38. https://www.ncbi.nlm.nih.gov/pubmed/28818202
  2. Zoller B, Ji Jianguang, Sundquist J, et al. Risk of coronary heart disease in patients with cancer: A nationwide follow-up study from Sweden. Eur J Cancer 2012;48:121-128. https://www.ncbi.nlm.nih.gov/pubmed/22023886
  3. Naschitz JE, Yeshurun D, Abrahamson J, et al. Ischemic heart disease precipitated by occult cancer. Cancer 1992;69:2712-20. https://www.ncbi.nlm.nih.gov/pubmed/1571902
  4. Lee EC, Cameron SJ. Cancer and thrombotic risk: the platelet paradigm. Frontiers in Cardiovascular Medicine 2017;4:1-6. https://www.ncbi.nlm.nih.gov/pubmed/29164134
  5. Lee V, Gilbert JD, Byard RW. Marantic endocarditis-A not so benign entity. Journal of Forensic and Legal Medicine 2012;19:312-15. https://www.ncbi.nlm.nih.gov/pubmed/22847046
  6. Nielsen VG, Lemole GM, Matika RW, et al. Brain tumors enhance plasmatic coagulation: the role of hemeoxygenase-1. Anesth Analg 2014;118919-24. https://www.ncbi.nlm.nih.gov/pubmed/24413553
  7. Thalin C, Blomgren B, Mobarrez F, et al. Trousseau’s syndrome, a previously unrecognized condition in acute ischemic stroke associated with myocardial injury. Journal of Investigative Medicine High Impact Case Reports.2014. DOI:10.1177/2324709614539283. https://www.ncbi.nlm.nih.gov/pubmed/26425612
  8. Samuels MA, King MA, Balis U. CPC, Case 31-2002. N Engl J Med 2002;347:1187-94. https://www.nejm.org/doi/pdf/10.1056/NEJMcpc020117?articleTools=true

If you liked this post, sign up under MENU and get future pearls freshly delivered into your mailbox!

My patient with brain tumor suffered a myocardial infarction (MI) just before having a diagnostic brain surgery. Could the tumor have placed him at higher risk of a coronary event?

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

FA Manian MD, MPH, , , , , , , , , , , , , , , , Leave a comment

Absolutely! Mediastinal irradiation is associated with several cardiac complications, including coronary artery disease, pericarditis, systolic or diastolic dysfunction and valvular disease. Valvular disease may occur in 2-37% of patients after mediastinal irradiation, is dose-dependent, and generally does not manifest until 10-20 years after the radiation exposure.1 Since mediastinal irradiation is common in young adults diagnosed with Hodgkin’s lymphoma, these complications may be seen in early middle-age or later.

Valvular retraction is usually the first radiation-induced valvular change, and most commonly leads to mitral and aortic valve regurgitation.2 This retraction tends to occur within 10 years of the radiation therapy, followed by fibrosis and calcification of the valves after 20 years.

Although the pathophysiology of radiation-induced valvular disease is not entirely understood, activation of fibrogenic growth factors (eg, tissue growth factor β1 and myofibroblasts) which promote the synthesis of collagen has been postulated.1 Additionally, irradiation of aortic interstitial cells has been shown to cause transformation to an osteogenic phenotype that produces bone morphogenic protein 2, osteopontin and alkaline phosphatase, all important factors in bone formation and possibly valvular calcification.3

Since radiation-induced heart disease is the most common cause of non-malignant morbidity and mortality in patients who have undergone mediastinal irradiation, some have recommended screening of asymptomatic patients for valvular disease every 5 years by echocardiography beginning 10 years after radiation therapy. 2  If an abnormality is found, the screening frequency should increase to every 2-3  years,  if the valvular abnormality is mild, or annually if the abnormality is moderate. For severe valvular abnormalities, the patients should be considered for valve replacement.

If you liked this post, sign up under MENU and get future pearls straight into your mailbox!

References

    1. Gujral DM, Lloyd G, Bhattacharyya S. Radiation-induced valvular heart disease. Heart 2016;102:269–276. https://heart.bmj.com/content/heartjnl/102/4/269.full.pdf
    2. Cuomo JR, Sharma GK, Conger PD, Weintraub NL. Novel concepts in radiation-induced cardiovascular disease. World J Cardiol. 2016; 8 (9):504-519. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5039353/
    3. Nadlonek NA, Weyant MJ, Yu JA, et al. Radiation induces osteogenesis in human aortic valve interstitial cells. J Thorac Cardiovasc Surg 2012;144:1466–70. doi:10.1016/j.jtcvs.2012.08.041 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3665422/

Contributed by Rachel Wallwork, MD, Mass General Hospital, Boston, MA

 

My middle-aged patient with a history of mediastinal irradiation for Hodgkin’s lymphoma in his 20s now has moderate aortic regurgitation. Could his valvular disease be related to the radiation he received over 20 years ago?

Why was the myocardial infarction in my postop patient silent?

FA Manian MD, MPH, , , , , , , , , , , , , , , Leave a comment

Myocardial infarction (MI) in postop patients is in fact usually silent (1,2) but what is less clear is how myocardial ischemia can occur without any symptoms.

Although use of analgesics and narcotics postop may dampen or mask chest pain or other symptoms associated with MI, other factors are also likely to play an important role, such as decreased sensitivity to painful stimuli, autonomic neuropathy (eg, in diabetes mellitus), and higher pain threshold among some patients (3).

Additional factors associated with silent MIs include cerebral cortical dysfunction since frontal cortical activation appears to be necessary to experience cardiac pain. Mental stress is also a frequent trigger for asymptomatic myocardial ischemia, infarction and sudden cardiac death (4).  High levels of beta-endorphin, an endogenous opiate, may also play a role (5).

 
Perhaps the most intriguing explanation for lack of symptoms is the observation that the levels of anti-inflammatory cytokines (interleukin-4 and -10)—which block pain transmission pathways and increase the threshold for nerve activation—seem to be increased in patients with silent myocardial ischemia (6).  Even more relevant to our postop patient is the finding that interleukin-10 production increases during and after major abdominal surgery and correlates with the amount of intraoperative blood loss (7). 

No wonder MIs in postop patients are often silent!

References
1. Devereaux PJ, Xavier D, Pogue J, et al. Characteristics nd short-term prognosis of perioperative myocardial infarction in patients undergoing noncardiac surgery: a cohort study. Ann Intern Med 2011;154:523-8. https://annals.org/aim/article-abstract/746934/characteristics-short-term-prognosis-perioperative-myocardial-infarction-patients-undergoing-noncardiac 
2. Badner NH, Knill RL, Brown JE, et al. Myocardial infarction after noncardiac surgery. Anesthesiology 1998;88:572-78. http://anesthesiology.pubs.asahq.org/article.aspx?articleid=1948483
3. Ahmed AH, Shankar KJ, Eftekhari H, et al. Silent myocardial ischemia:current perspectives and future directions. Exp Clin Cardiol 2007;12:189-96. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2359606/ 
4. Gullette EC, Blumenthal JA, Babyak M, et al. Effects of mental stress on myocardial ischemia during daily life. JAMA 1997;277:1521-6. https://jama.jamanetwork.com/journals/jama/articlepdf/416233/jama_277_19_029.pdf
5. Hikita H, Kurita A, Takase B, et al. Re-examination of the roles of beta-endorphin and cardiac autonomic function in exercise-induced silent myocardial ischemia. Ann Noninvasive Electrocardiol 1997;2:319-25. https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1542-474X.1997.tb00195.x
6. Mazzone A, Cusa C, Mazzucchelli I, et al. Increased production of inflammatory cytokines in patients with silent myocardial ischemia. J Am Coll Cardiol 2001;38:1895-901. https://www.ncbi.nlm.nih.gov/pubmed/11738291
7. Kato M, Honda I, Suzuki H, et al. Interleukin-10 production during and after upper abdominal surgery. J Clin Anesth 1998;10:184-8. https://www.ncbi.nlm.nih.gov/pubmed/9603586 

If you liked this post, sign up under MENU and catch future pearls straight into your mailbox! 

Why was the myocardial infarction in my postop patient silent?

My hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?

FA Manian MD, MPH, , , , , , , , , Leave a comment

Yes! Ample epidemiological studies implicate infection as an important risk factor for MI.1 The increased risk of MI has been observed during the days, weeks, months or even years following an infection.

A 2018 paper reported a several-fold risk of MI during the week after laboratory-confirmed infection caused by a variety of respiratory pathogens such as influenza virus (6-fold), respiratory syncytial virus (4-fold), and other respiratory viruses (3-fold). 2 Among patients hospitalized for pneumococcal pneumonia, 7-8% may suffer an MI.3,4 One study found a 48-fold increase in the risk of MI during the first 15 days after hospitalization for acute bacterial pneumonia.5 Similarly, an increase in the short-term risk of MI has been observed in patients with urinary tract infection and bacteremia.6

The risk of MI appears to be the highest at the onset of infection and correlates with the severity of illness, with the risk being the highest in patients with pneumonia complicated by sepsis, followed by pneumonia and upper respiratory tract infection. Among patients with pneumonia, the risk exceeds the baseline risk for up to 10 years after the event, particularly with more severe infections.1

Potential mechanisms of MI following infections include release of inflammatory cytokines (eg, interleukins 1, 6, tumor necrosis factor alpha) causing activation of inflammatory cells in atherosclerotic plaques, in turn resulting in destabilization of the plaques. In addition, the thrombogenic state of acute infections, platelet and endothelial dysfunction may increase the risk of coronary thrombosis at sites of plaque disruption beyond clinical resolution of the acute infection. 1

Liked this post? Download the app on your smartphone and sign up under MENU to get future pearls straight into your inbox, all for free!

 

References

  1. Musher DM, Abers MS, Corrales-Medina VF. Acute infection and myocardial infarction. N Engl J Med 2019;380:171-6. https://www.ncbi.nlm.nih.gov/pubmed/30625066
  2. Kwong JC, Schwartz KL, Campitelli MA, et al. Acute myocardial infarction after laboratory-confirmed influenza infection. N Engl J Med 2018;378:345-53. https://www.nejm.org/doi/full/10.1056/NEJMoa1702090
  3. Musher DM, Alexandraki I, Graviss EA, et al. Bacteremic and nonbacteremic pneumococcal pneumonia: a prospective study. Medicine (Baltimore) 2000;79:210-21. https://www.ncbi.nlm.nih.gov/pubmed/10941350
  4. Musher DM, Rueda Am, Kaka As, Mapara SM. The association between pneumococcal pneumonia and acute cardiac events. Clin Infect Dis 2007;45:158-65. https://www.ncbi.nlm.nih.gov/pubmed/17578773
  5. Corrales-Medina VF, Serpa J, Rueda AM, et al. Acute bacterial pneumonia is associated with the occurrence of acute coronary syndromes. Medicine (Baltimore) 2009;88:154-9. https://www.ncbi.nlm.nih.gov/pubmed/19440118
  6. Dalager-Pedersen M, Sogaard M, Schonheyder HC, et al. Risk for myocardial infarction and stroke after community-acquired bacteremia: a 20-year population-based cohort study. Circulation 2014;129:1387-96. https://www.ncbi.nlm.nih.gov/pubmed/24523433

 

My hospitalized patient with pneumonia has now suffered an acute myocardial infarction (MI). Can acute infection and MI be related?

How can I distinguish cardiac asthma from typical bronchial asthma?

FA Manian MD, MPH, , , , , , , , Leave a comment

Certain clinical features of cardiac asthma, defined as congestive heart failure (CHF) associated with wheezing, may be useful in distinguishing it from bronchial asthma, particularly in older patients with COPD (1-3).

• Paroxysmal nocturnal dyspnea associated with wheezing
• Presence of rales or crackles, ascites or other signs of CHF
• Poor response to bronchodilators and corticosteroids
• Formal pulmonary function test with bronchoprovocation demonstrating minimal methacholine response.

Cardiac asthma is not uncommon. In a prospective study of patients 65 yrs of age or older (mean age 82 yrs) presenting with dyspnea due to CHF, cardiac asthma was diagnosed in 35% of subjects. Even in non-elderly patients, cardiac asthma has been reported in 10-15% of patients with CHF (2).

The mechanism(s) underlying cardiac asthma is likely multifactorial. Pulmonary edema and pulmonary vascular congestion have traditionally been considered as key factors either through edema in the interstitial fluid of bronchi squeezing the bronchiolar lumen or by externally compressing the entire airway structure and the bronchiole wall. Reflex bronchoconstriction involving the vagus nerve, bronchial hyperreactivity, systemic inflammation, and airway remodeling may also play a role (1,3). 

Treatment of choice for cardiac asthma typically includes diuretics, nitrates and morphine, not bronchodilators or corticosteroids (1,3). 

Bonus Pearl: Did you know that the term “cardiac asthma” was first coined by the Scottish physician, James Hope, way back in 1832 to distinguish it from bronchial asthma!

Liked this post? Download the app on your smart phone and sign up below to catch future pearls right into your inbox, all for free!

Subscribe to Blog via Email

Enter your email address to subscribe to this blog and receive notifications of new posts by email.

References
1. Litzinger MHJ, Aluen JKN, Cereceres R, et al. Cardiac asthma: not your typical asthma. US Pharm. 2013;38:HS-12-HS-18. https://www.uspharmacist.com/article/cardiac-asthma-not-your-typical-asthma
2. Jorge S, Becquemin MH, Delerme S, et al. Cardiac asthma in elderly patients: incidence, clinical presentation and outcome. BMC Cardiovascular Disorders 2007;7:16. https://www.ncbi.nlm.nih.gov/pubmed/17498318
3. Tanabe T, Rozycki HJ, Kanoh S, et al. Cardiac asthma: new insights into an old disease. Expert Rev Respir Med 2012;6(6), 00-00. https://www.ncbi.nlm.nih.gov/pubmed/23234454

How can I distinguish cardiac asthma from typical bronchial asthma?