Plasma Levels of Atrial Natriuretic Peptide in Hypertrophic Cardiomyopathy Giorgio Derchi, MD, Pietro Bellone, MD, Franc0 Chiarella, MD, Matilde Randazzo, BS, Vera Zino, BS, and Carlo Vecchio, MD he most typical physiopathologicabnormality in hypertrophic cardiomyopathy (HC) is diastolic dysT function, characterized by abnormal stiffnessof the left ventricle during diastole,with resultant impaired ventricular filling. This abnormality in diastolic relaxation results in elevationof left ventricular end-diastolicpressure. Impaired early diastolic filling as well as abnormal distensibility leadsto a compensatoryincreasein the contribution of atria1 systole to left ventricular fdling.1 Atria1 natriuretic peptide (ANP) is a cardiac polypeptideexerting potent diuretic, natriuretic and vasodilatory activities, and is producedand secretedpredominantly by the atria in responseto volwne or pressureoverload.2SThe mechanism of ANP releasehas been attributed to increasesin either atria1pressuresor atria1distension.4*5 PlasmaANP levelsare increasedin patients with congestiveheart failure and correlate well with left ventricular end-diastolic pressure and atria1 pressure in patients with thii disease.671 Experimental data provideevidenceof ventricular activation of the ANP gene in ventricular overload. A recent report8indicated that ventricular ANP expression occurs as a responseto disease-specificchangessuch as myocardial fiber disarray, hypertrophy of myocytesand fibrosis in HC.8 Plasma ANP levels have not yet been investigatedand related to the clinical status in HC. The purposeof this study was to verify whether an increasein plasma ANP levels in patients with HC exists and to establish a possiblecorrelation betweenANP levels and clinical anatomic status of patients with HC. The study group consistedof 30 patients (21 men, 9 womenaged 13 to 74 years, mean 43 f 18) with HC in ambulatory follow-up at the Cardiology Division, E.O. Ospedali Galliera, Genoa,Italy. Thirteen patients were receiving antiarrhythmic drugs. The control group consisted of 50 normal subjects (30 men, 20 womenaged 8 to 70 years, mean 42 f 19). All normal subjects had a normal rest electrocardiogram, chestx-rays, ventricular diameters and wall motion by 2-dimensional echocardiography. Each patient was classified according to the criteria of New York Heart Associationfunctional class. Of the 30 patients with HC, 20 were designated New York Heart Association class I, 5 were class II, 4 were class III and 1 was class IV. Body surface area ranged from 1.3 to 2.05 m2. After echocardiographicexamination (30 minutes in the supine position), blood samples were collected and analyzedfor ANP concentration.Blood wasdrawnfrom all patients in the morning via an antecubital vein, after From the Cardiology Division and Nuclear Medicine Service, E.O. Ospedali Galliera, Via Volta 8, 16128Genova, Italy. Manuscript re ccived April 13, 1992;revisedmanuscript receivedand acceptedJune 15, 1992.

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THE AMERICAN JOURNAL OF CARDIOLOGY VOLUME 70

30 minutes in the supineposition and after an overnight fat. Blood samples were collected in pre-chilled test tubes containing ethylenediaminetetraacetic acid-2Na and 500 kIU of aprotine. Plasma isolated by low-temperature centrtfugation was stored at -70°C and ANP levelswerelater determinedby a commercially available kit from Eiken Chemical Co., Tokyo, Japan. Reference values in our laboratory are: 50 f 12 pglml (range 20 to 77). Values are expressed as mean f SD. Differences betweenmeanswerecomparedusing unpaired Student’s t test. Upper and lower 95% normal confidencelimits for the echocardiographic data were calculated from a 2tailed Student’s t test distribution by using thefollowing formulas: mean + (2.042 X SD) and mean - (2.042 X SD). Regression analysis was applied to examine the relation between2 variables as appropriate. A p value x0.05 was consideredsignificant. Echocardiographic data revealed significantly hypertrophic ventricles and increasedatria1 dimension in patients with HC comparedwith normal subjects. Table I summarizes the echocardiographic data for all patients. No differencesoccurred in left ventricular internal diameters.Left ventricular outjlow tract obtruction was presentin 11 of the 30patients with HC (mild in 4, severe in 7). Mild mitral regurgitation waspresent in 10 of the 30patients with HC. New York Heart Association class rangedfrom I to IVwith a median value in classI. Mean plasma ANP concentrationof the group of patients with HC was significantly higher than that of the control group (101 f 88 us 53 f 18 pglml; p 20 mm/m3 waspresent in all patients in New York Heart Association class ZZZto IV and in 9 of 24 patients in New York Heart Association class Z to ZZ (26%). Figure 1 showsthe relation betweenthe degreeof left atria1 cavity enlargement and plasma ANP levels (r = 0.64,p