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High prevalence of intramural coronary infection in patients with drug-resistant cardiac syndrome X: comparison with chronic stable angina and normal controls
  1. Cristina Chimenti1,2,3,
  2. Patrizio Sale3,4,
  3. Romina Verardo2,
  4. Stefania Cicalini5,
  5. Nicola Petrosillo5,
  6. Matteo A Russo3,4,
  7. Francesco Fedele1,
  8. Andrea Frustaci1,2
  1. 1Cardiovascular and Respiratory Sciences Department, La Sapienza University, Rome, Italy
  2. 2The Molecular and Cellular Cardiology Laboratory, IRCCS “Lazzaro Spallanzani”, Rome, Italy
  3. 3The Experimental Medicine and Pathology Department, La Sapienza University, Rome, Italy
  4. 4The IRCCS San Raffaele La Pisana, Rome, Italy
  5. 5The “2nd Infectious Disease Unit”, IRCCS L Spallanzani, Rome, Italy
  1. Correspondence to Dr Andrea Frustaci, Cardiovascular and Respiratory Sciences Department, La Sapienza University, Viale del Policlinico 155, Rome 00161, Italy; biocard{at}


Background Coronary microvascular dysfunction has been reported along with myocardial viral infection. Whether intramural coronary vessels infection plays a role in patients with cardiac syndrome X (CSX) is unknown.

Methods Thirteen consecutive patients (four men, nine women, mean age 51±10.5 years) with drug-resistant CSX underwent left ventricular endomyocardial biopsy. Myocardial tissue was examined for histology, immunohistochemistry and for the presence of cardiotropic viruses by PCR analysis. In the presence of a viral infection on the whole tissue, laser microdissection was performed to analyse the viral genome selectively in intramural vessels and cardiomyocytes. Controls were surgical cardiac biopsies from patients with chronic stable angina and from patients with mitral stenosis and normal cardiac function (normal controls).

Results Histology showed hypertrophy and degeneration of cardiomyocytes with interstitial and replacement fibrosis in all CSX, while focal lymphocytic myocarditis was additionally recognised in three patients. No vasculitis was observed. Viral genomes were detected in nine of 13 CSX (Epstein–Barr virus in four, adenovirus in three, human herpes virus (HHV) 6 in one, Epstein–Barr adenovirus co-infection in one). Laser microdissection showed that Epstein–Barr and adenovirus localised both in cardiomyocytes and intramural vessels, while HHV-6 infection was confined to the vessel wall.

Conclusions Viral genomes can be detected in intramural vessels of up to 69% of drug-resistant CSX. Coronary small vessels infection represents an alternative pathophysiological mechanism of this syndrome and can explain the poor response to anti-ischaemic drugs.

  • Coronary microcirculation
  • endomyocardial biopsy
  • laser microdissection
  • microvascular
  • myocarditis
  • syndrome X
  • virus

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  • Funding This study was funded by grant EX ART.56 entitled ‘HIV-related and unrelated inflammatory cardiomyopathy: identification of causal agents and pathogenetic mechanisms providing a tailored therapy’.

  • Competing interests None.

  • Patient consent Obtained.

  • Ethics approval This study was conducted with the approval of La Sapienza University.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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