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?

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

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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?

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

 

Patients with atrial fibrillation (AF) who need percutaneous coronary intervention (PCI) after acute coronary syndrome or for stable angina pose a treatment challenge as oral anticoagulants (OACs) and dual antiplatelet therapy (DAPT) are often used concurrently to decrease the risk of systemic thromboembolism and stent thrombosis. However, “triple therapy”, including aspirin, a P2Y12 inhibitor, and an OAC (eg, warfarin or a direct oral anticoagulant-DOAC), also increases the risk of bleeding, necessitating several recent landmark trials to better address the subject.

Two modest-sized RCTs (WOEST and ISAR-TRIPLE) reported that when compared to triple therapy (DAPT plus warfarin), double therapy (single antiplatelet agent plus INR-targeted warfarin) is associated with reduced risk of bleeding complications without an increased risk of thrombotic events. 1,2

Two larger RCTs, PIONEER AF-PCI and RE-DUAL PCI, studied rivaroxaban and dabigatran, respectively, in patients with non-valvular AF undergoing PCI and found a reduction in bleeding events in patients receiving double therapy (single antiplatelet agent plus DOAC) compared to triple therapy (DAPT plus warfarin), without an increased risk of thrombotic complications. 3,4

Collectively, these studies suggest that it may be safe to treat patients with increased risk of bleeding with double therapy (even immediately following PCI) without an increase in thrombotic events. If triple therapy is elected, duration should be minimized, clopidogrel should be preferred over more potent P2Y12 inhibitors, and a PPI should be considered.

 

References:

  1. Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet. 2013;381:1107-15. https://www.ncbi.nlm.nih.gov/pubmed/23415013
  2. Fiedler KA, Maeng M, Mehilli J, et al. Duration of triple therapy in patients requiring oral anticoagulation after drug-eluting stent Implantation: The ISAR-TRIPLE Trial. J Am Coll Cardiol. 2015;65:1619-29. https://www.ncbi.nlm.nih.gov/pubmed/25908066
  3. Gibson CM, Mehran R, Bode C, et al. Prevention of bleeding in patients with atrial fibrillation undergoing PCI. N Engl J Med. 2016;375:2423-2434. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1611594
  4. Cannon CP, Bhatt DL, Oldgren J, et al. Dual antithrombotic therapy with dabigatran after PCI in atrial fibrillation. N Engl J Med. Published online, Aug, 27, 2017. http://www.nejm.org/doi/pdf/10.1056/NEJMoa1708454

 

Contributed by Amulya Nagarur, MD, Mass General Hospital, Boston, MA

In my patient on oral anticoagulation about to undergo coronary stenting, will triple therapy (an oral anticoagulant plus two antiplatelet agents) be necessary or can I get away with double therapy (an oral anticoagulant plus a single antiplatelet agent)?

When should I suspect spontaneous coronary artery dissection in my patient with chest pain?

Spontaneous coronary artery dissection (SCAD) is defined as the separation of the walls of the coronary artery.1 It is thought that hemorrhage into the false lumen can result in compression of the true lumen, leading to ischemia. Although its exact incidence is unknown, SCAD has been estimated to account for up to 35% of myocardial infarctions in women younger than 50 y of age.2-3

SCAD is often associated with acute chest pain with presentations ranging from acute coronary syndrome (ACS) to sudden cardiac death.1,4 Diagnosis is typically accomplished with coronary angiography and, increasingly, newer modalities such as optical coherence tomography, intravascular ultrasound, and cardiac CT angiography.1

Clinical features that should raise suspicion of SCAD are shown (Table)5. Among many risk factors, myocardial infarction in younger women and the absence of traditional cardiovascular risk factors or lack of typical atherosclerotic lesions in coronary arteries should be potential flags for the possibility of SCAD.

Although the optimal management of SCAD is unclear, conservative therapy with aspirin, clopidogel and beta-blockers has often been recommended5 .  Percutaneous coronary intervention (PCI) carries a risk of worsening the dissection or causing additional dissections in such patients1. Revascularization is often reserved for those with hemodynamic instability, persistent ischemia, sustained ventricular tachycardia or fibrillation, or left main dissection.1,5

Table. Clinical features that raise suspicion of SCAD5 ______________________________________________________________________________________________________________
Myocardial infarction in young women (especially age ≤ 50 y)
Absence of traditional cardiovascular risk factors
Little or no evidence of typical atherosclerotic lesions in coronary arteries
Peripartum state
History of fibromuscular dysplasia
History of relevant connective tissue disorder (eg, Marfan’s syndrome, Ehler Danlos syndrome)
History of relevant systemic inflammation (incl. SLE, IBD, sarcoidosis, polyarteritis nodosa)
Precipitating stress events caused by emotional or intense physical factors ______________________________________________________________________________________________________________
SLE: Systemic lupus erythematosus; IBD: Inflammatory bowel disease (eg, Crohn’s, ulcerative colitis).

References

  1. Saw J, Mancini GB, Humphries KH. Contemporary Review on Spontaneous Coronary Artery Dissection. J Am Coll Cardiol 2016;68:297-312.
  2. Rashid HN, Wong DT, Wijesekera H, et al. Incidence and characterisation of spontaneous coronary artery dissection as a cause of acute coronary syndrome – a single-centre Australian experience. Int J Cardiol 2016;202:336-8.
  3. Nakashima T, Noguchi T, Haruta S, et al. Prognostic impact of spontaneous coronary artery dissection in young female patients with acute myocardial infarction: a report from the Angina Pectoris-Myocardial Infarction Multicenter Investigators in Japan. Int J Cardiol 2016;207:341-8.
  4. Lettieri C, Zavalloni D, Rossini R, et al. Management and long-term prognosis of spontaneous coronary artery dissection. Am J Cardiol 2015;116:66-73.
  5. Yip A, Saw J. Spontaneous coronary artery dissection-A review. Cardiovasc Diagn Ther 2015;5:37-48. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4329168/pdf/cdt-05-01-037.pdf

Contributed by Mahesh Vidula, MD, Mass General Hospital, Boston, MA.

When should I suspect spontaneous coronary artery dissection in my patient with chest pain?

Does marijuana use lead to any adverse cardiovascular effects?

Although marijuana is often not considered to have serious cardiovascular effects, in animal studies THC, the active ingredient in cannabis, has been found to affect cardiovascular activity through a number of mechanisms, including inhibition of adrenal catecholamine secretion and modulation of cardiac vagal tone through inhibition of norepinephrine release from sympathetic neurons (1).

There have also been reports of temporal association between marijuana use and acute coronary syndrome, cardiac arrhythmias, cerebrovascular events, including TIA’s, strokes, and cerebral vasospasm, as well as peripheral vascular events, including arteritis, Raynaud’s phenomenon, and digital necrosis (2).

In a recent comprehensive case series, about 2.0 % of all cannabis-associated adverse events were reported cardiovascular in nature, with 25% resulting in death (2). However, it is often difficult to determine the relative contribution of marijuana and other concurrent conditions or substances (e.g. alcohol and tobacco) when cardiovascular complications occur. More research in this area is needed.

References

1. Szabo B, Nordheim U, Niederhoffer N. Effects of cannabinoids on sympathetic and parasympathetic neuroeffector transmission in the rabbit heart. J Pharmacol ExpTher 2001; 297:819-826. http://jpet.aspetjournals.org/content/297/2/819

2. Jouanjus E, Lapeyre-Mestre M, Micallef J, et al. Cannabis use: signal of increasing risk of serious cardiovascular disorders. J Am Heart Assoc 2014; 3:e000638.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4187498/

Contributed by Pierre Ankomah, MD, Boston, MA

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Does marijuana use lead to any adverse cardiovascular effects?