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CLINICAL RESEARCH: HYPERTROPHIC CARDIOMYOPATHY

Reversal of Inappropriate Peripheral Vascular Responses in Hypertrophic Cardiomyopathy

Rajesh Thaman, MD, MRCP^_*,,_*, Perry M. Elliott, MD, MRCP, FACC^_*,, Jaymin S. Shah, MD, MRCP^_*,, Bryan Mist, PhD^_*,, Lynne Williams, MRCP, Ross T. Murphy, MD, MRCP^_*,, William J. McKenna, MD, FRCP, FACC^_*, and Michael P. Frenneaux, MD, FRCP, FACC

^_* Department of Cardiological Sciences, St. George’s Hospital Medical School, London, United Kingdom
The Heart Hospital, University College London, London, United Kingdom
Department of Cardiovascular Medicine, University of Birmingham, Birmingham, United Kingdom

Manuscript received August 31, 2004; revised manuscript received March 17, 2005, accepted April 19, 2005.

^_* Reprint requests and correspondence: Dr. Rajesh Thaman, The Heart Hospital, Cardiology, 16-18 Westmoreland Street, London, W1G 8PH, United Kingdom. (Email: rajesh.thaman{at}uclh.nhs.uk).

OBJECTIVES: 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.

Abbreviations and Acronyms   ABPR = abnormal blood pressure response   BRS = baroreceptor sensitivity   FBF = forearm blood flow   FVR = forearm vascular resistance   HCM = hypertrophic cardiomyopathy   LBNP = lower body negative pressure   LV = left ventricle/ventricular   NBPR = normal blood pressure response   SBP = systolic blood pressure   SVR = systemic vascular resistance   VO2 = oxygen consumption   %VO2max = percentage of the predicted maximal VO2

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