title: Left ventricular outflow tract gradient is associated with reduced capillary density in hypertrophic cardiomyopathy irrespective of genotype.
abstract: BACKGROUND
  Coronary microvascular dysfunction (CMD) is an important feature of hypertrophic cardiomyopathy (HCM), which contributes negatively to symptoms and long-term outcome. Previous in vivo imaging studies in HCM suggest that left ventricular outflow tract (LVOT) gradient and genetic status are important contributors to CMD. CMD may be caused by reduced capillary density. Here, we investigated whether a reduction in capillary density is related to genetic status or LVOT gradient severity in an in vitro study of HCM cardiac samples.
  
  
  METHODS
  Using immunofluorescence microscopy, we analysed capillaries (Cap) and cardiomyocytes (CM) in myectomy specimens from 18 HCM patients with maximum left ventricular (LV) wall thickness ≥15 mm. All subjects exhibited significant LVOT obstruction, necessitating septal myectomy. In addition, control myocardium from the LV septal wall was collected at autopsy of 6 individuals that suffered a noncardiac death.
  
  
  RESULTS
  CM area was higher in patients with HCM compared to controls. Capillary density was significantly lower in patients with HCM compared with controls (1425 ± 262 vs. 2543 ± 509 Cap/mm(2) , P < 0·001), as was the number of Cap per CM corrected for CM area (2·2 ± 0·5 vs. 4·2 ± 0·9 Cap/CM area, P < 0·001). Capillary density did not differ between genotype-negative and genotype-positive HCM patients at similar resting LVOT gradients. A significant correlation was present between resting LVOT gradient and CM area (r = 0·73, P < 0·001), capillary density (r = -0·74, P < 0·001) and the number of Cap per CM corrected for CM area (r = -0·82, P < 0·001).
  
  
  CONCLUSIONS
  Our data indicate that LVOT gradient, rather than genetic status, is associated with reduced capillary density in HCM.
authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.|ICIN-The Netherlands Heart Institute, Utrecht, The Netherlands.
authors.forename: Ahmet
authors.initials: A
authors.lastname: Güçlü
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.|Department of Pulmonology, Institute for Cardiovascular Research (ICaR-VU), VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Chris
authors.initials: C
authors.lastname: Happé
authors.affiliation: Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Seyma
authors.initials: S
authors.lastname: Eren
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Ibrahim H
authors.initials: IH
authors.lastname: Korkmaz
authors.affiliation: Department of Pathology and Cardiac Surgery, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Hans W M
authors.initials: HW
authors.lastname: Niessen
authors.affiliation: Department of Cardiothoracic Surgery, Sint Antonius Hospital, Nieuwegein, The Netherlands.
authors.forename: Patrick
authors.initials: P
authors.lastname: Klein
authors.affiliation: Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Marjon
authors.initials: M
authors.lastname: van Slegtenhorst
authors.affiliation: Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Arend F
authors.initials: AF
authors.lastname: Schinkel
authors.affiliation: Thorax Center, Department of Cardiology, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Michelle
authors.initials: M
authors.lastname: Michels
authors.affiliation: Department of Cardiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Albert C
authors.initials: AC
authors.lastname: van Rossum
authors.affiliation: Medical Center Alkmaar, Alkmaar, The Netherlands.
authors.forename: Tjeerd
authors.initials: T
authors.lastname: Germans
authors.affiliation: ICIN-The Netherlands Heart Institute, Utrecht, The Netherlands.|Department of Physiology, VU University Medical Center, Amsterdam, The Netherlands.
authors.forename: Jolanda
authors.initials: J
authors.lastname: van der Velden
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002196:Capillaries / Q000473:pathology*; D002312:Cardiomyopathy, Hypertrophic / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D014694:Ventricular Outflow Obstruction / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology; D055815:Young Adult
keywords: Capillary density; hypertrophic cardiomyopathy; hypertrophy; microvascular dysfunction