Reversal of inappropriate peripheral vascular responses in hypertrophic cardiomyopathy.
OBJECTIVE
We assessed the frequency of abnormal forearm vasodilator responses during lower body negative pressure (LBNP) in 21 non-obstructive hypertrophic cardiomyopathy (HCM) patients (31 +/- 8 [20 to 43] years) with abnormal blood pressure response (ABPR) to exercise and the effects of three drugs used to treat vasovagal syncope (propranolol, clonidine, and paroxetine) in a double-blind crossover study.


BACKGROUND
Some HCM patients have an ABPR to exercise, which may be due to paradoxical peripheral vasodilatation. A similar proportion has paradoxical forearm vasodilatation during central volume unloading using LBNP. These abnormal reflexes may be caused by left ventricular mechanoreceptor activation. Similar mechanisms may also contribute to some cases of vasovagal syncope.


METHODS
Blood pressure changes were assessed during exercise, and forearm vascular responses and baroreceptor sensitivity were assessed during LBNP using plethysmography.


RESULTS
Nine (43%) patients (group A) had paradoxical vasodilator responses (forearm vascular resistance [FVR] fell by 7.5 +/- 4.6 U), and 12 (57%) patients (group B) had normal vasoconstrictor responses during LBNP (FVR increased by 7.7 +/- 4.9 U). Paroxetine augmented systolic blood pressure (SBP) during exercise in group A (21 +/- 6 mm Hg vs. 14 +/- 11 mm Hg at baseline, p = 0.02); no effect was detected in group B. Paroxetine reversed paradoxical vascular responses during LBNP in seven (78%) patients from group A. Propranolol and clonidine had no significant effect on SBP during exercise but reversed paradoxical vascular responses in some patients from group A (n = 5 and n = 3).


CONCLUSIONS
Paradoxical vasodilatation during LBNP occurs in 40% of patients with ABPR during exercise and is reversed by propranolol, clonidine, and paroxetine. Paroxetine also improved SBP response to exercise.
Thaman
Rajesh
R
Department of Cardiological Sciences, St. George's Hospital Medical School, London, United Kingdom. rajesh.thaman@uclh.nhs.uk
Elliott
Perry M
PM
Shah
Jaymin S
JS
Mist
Bryan
B
Williams
Lynne
L
Murphy
Ross T
RT
McKenna
William J
WJ
Frenneaux
Michael P
MP
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000503:physiopathology*; D003000:Clonidine / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D005080:Exercise Test; D005260:Female; D006801:Humans; D035002:Lower Extremity / Q000503:physiopathology; D008297:Male; D017374:Paroxetine / Q000494:pharmacology / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D019462:Syncope, Vasovagal / Q000209:etiology / Q000517:prevention & control; D014664:Vasodilation / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D017374:Paroxetine; D011433:Propranolol; D003000:Clonidine