ID: 6: HYPERTROPHIC OBSTRUCTIVE CARDIOMYOPATHY IN THE SETTING OF SYSTEMIC SCLERODERMA

Restrictive cardiomyopathy has been a common variant seen in systemic sclerosis (SS) with myocardial fibrosis. The association of SS with restrictive cardiomyopathy has well been established, but that with HOCM is not clearly understood. Herein, we report a case of a patient with SS, identified to have both HOCM and myocardial fibrosis.A 54-year-old woman with systemic sclerosis, idiopathic lung disease with moderate pulmonary hypertension, presented with fatigue, decreased appetite and shortness of breath. Vital signs were significant for oxygen saturation of 86% on room air, tachycardia of 117 bpm, and blood pressure of 110/53 mm Hg. Physical examination revealed diffuse rhonchi in all lung fields, malar rash and skin excoriation in bilateral lower extremities without edema. Laboratory studies were significant for elevated brain natriuretic peptide (BNP) of 858 pg/mL. Transthoracic echocardiography revealed left ventricular hypertrophy (LVH) with ejection fraction of 78%. Electrocardiography illustrated LVH. Cardiac magnetic resonance imaging (cMRI) was significant for severe left ventricular cardiac asymmetric septal hypertrophy with outflow obstruction caused by anterior motion of the mitral valve. Cardiac biopsy revealed evidence of diffuse fibrosis, but did not show iron, glycogen, or amyloid depositions.Patient was maintained on mycophenolate mofetil, low dose of methylprednisolone, morphine, clonazepam and transferred to hospice care.Hypertrophic obstructive cardiomyopathy (HOCM) is the most common genetic cardiac disorder with an autosomal dominant transmission. It is characterized by asymmetric LVH out of proportion of systemic after load. The most common cardiac involvement in SS is myocardial fibrosis in a restrictive pattern, while HOCM is rarely seen in SS.Abstract ID: 6 Figure 1Cardiac MRI demonstrating hypertrophied ventricle with fibrosis. This image demonstrates the features of both hypertrophic and restrictive cardiomyopathy.

Diminished effect of cAMP on Ca2+ accumulation in skinned fibers of hypertrophied rat heart

Sarcoplasmic reticulum (SR) Ca2+ uptake is reduced in the hypertrophied ventricle. To determine whether events initiated by beta-adrenergic stimulation are involved, we compared the effects of adenosine 3',5'-cyclic monophosphate (cAMP) on SR Ca2+ uptake between normal and pressure-overloaded hypertrophied hearts using saponin-skinned rat left ventricular muscles. Left ventricular pressure overload was induced by partial ligation of the abdominal aorta for 4–6 wk before study. Age-matched normal rats served as controls. Pressure overload increased the left ventricular weight-to-body weight ratio 60.8%. The SR was loaded by exposing the muscles to 10(-6) M Ca2+ solution; SR Ca2+ release was induced by 5 or 25 mM caffeine, and the amount of Ca2+ released from the SR was estimated by the area under the caffeine-induced transient contraction. Concomitant exposure to 10(-4) M cAMP did not influence caffeine-induced Ca2+ release in either normal or hypertrophied fibers. When 10(-4) M cAMP was applied during the Ca(2+)-loading periods, the amount of Ca2+ accumulated by the SR increased in both normal and hypertrophied fibers. However, the extent of increase was significantly smaller in hypertrophied fibers than in normal fibers [10.9 +/- 1.7 and 27.4 +/- 5.3% in 1 min of Ca2+ loading (P < 0.05), 12.2 +/- 3.2 and 24.7 +/- 3.8% in 4 min of Ca2+ loading (P < 0.05), respectively]. cAMP (10(-4) M) shifted the force-pCa relationship to the right similarly in normal and hypertrophied muscles, and there was no difference in the force-pCa relationship between the two groups either with or without cAMP.(ABSTRACT TRUNCATED AT 250 WORDS)

Hypoxia-induced downregulation of beta-adrenergic receptors in rat heart

To test the desensitization hypothesis of cardiac beta-adrenergic receptors (beta-AR) in chronic hypoxia, the effect of 1, 3, 7, 15, and 21 days of exposure to hypobaric hypoxia (380 Torr) was evaluated in Wistar rats. Exposure to hypoxia for 1–15 days did not induce any change in right and left ventricular beta-AR density (Bmax) determined with [125I]iodocyanopindolol or in antagonist affinity. After 21 days, Bmax decreased by 24% in the left ventricle. In contrast, no change in beta-AR was shown in the right hypertrophied ventricle. Agonist affinity in the left ventricle was not altered, as shown by the analysis of displacement curves of isoproterenol (normoxia 185 +/- 26 nM, hypoxia 170 +/- 11 nM). Moreover, there was no significant decrease in adenylate cyclase activity (pmol.mg-1.min-1) in the left ventricle. In the right ventricle, a 21-day exposure to hypoxia led to a decrease in basal and maximal activity when stimulated by isoproterenol. A decrease in tissue norepinephrine content was observed after 7 days of hypoxia. In conclusion, these data support the beta-AR downregulation hypothesis as one of the mechanisms of myocardial adaptation to high altitude occurring after 2-3 wk of exposure to hypoxia. The regulation pathways of beta-AR may differ between left nonhypertrophied and right hypertrophied ventricles. No evidence of profound abnormality of signal transduction was shown.