Rapid Attenuation of Response to Nifedipine in Primary Pulmonary Hypertension

vascular maHormatioos must be confhmed angiographicaDy and should be treated de&nitively. This is the first reported case in which a nonsurgical approach has been used in the treatment of SAPA fistulae. EmbolU.ation is an alternative to surgery and should be considered in most cases.

SELECTED REFERENCES 1 Burchell HB, Claggett OT. The clinical syndrome associated with pulmonary arteriovenous fistulas, including a case report of tbe surgical cure. Am Heart J 1947; 34:151 ! Hearne SF, Burbank MK. Internal mammary artery-topulmonary artery fistulas. Circulation 1980; 62:1131-35 3 Bnmdage BH, Gomez AC, Cheitlin MD, Gmelich JT. Systemic artery-to-pulmonary artery fistulae: Report of two cases and review of the literature. Chest 1972: 62:19-23 4 Kerber CW. Flow-control therapeutic embolization: A physiologic and safe technique. AJR 1980; 134:557-61 5 Thurer RJ. Communication between the pulmonary and systemic circulations. Ann Thorac Surg 1975; 21:114-22 6 Rodbard S. Blood velocity and endocarditis. Circulation 1963; 27: 18-26 7 Gomes MR, Bematz PE, Dines DE. Pulmonary arteriovenous fistu1ae. Ann Thorac Surg 1969; 7:582-91

Rapid AHenuation of Response to Nifedipine in Primary Pulmonary Hypertension• Brvce A Wood, M.D.; FrancUco Tortoledo, M.D.; ]ert'fl

C. Luck, M.D.; and William H. FenneU. M.D.t

In a 22-year-old WOIDIUI wida prima'y palmoaary by• pertelllion resisCimt to .0 prevlo• attempts to rednc:e the palmoaary '98IICIIbr resl'duce, there w. dramde Improvement after tbe lnt dose of nlfedlplne, lO 1111 po, wblcb w. aot IUIDined with sabreqaent doses. While there ,.. • penillteDt red1ldloa Ia systemic: vasc:u1ar res11tance, the Initial dnJI-related reduction Ia pulmoaary 'ftiiC1IIao n*tace .,.. (II'Oinlllvely at· tennated with the lllhleqneat four doees of nlfedlplne,

CASE REPoRT A 22-year-old black woman was flrst admitted to this haspital in February, 1981 for progressive dyspnea on eurtioa and Dear syncopal episodes. These had begun approximately flve months prior to her admission when she noted dyspnea on climbing stairs. Physical examination revealed the presence of a right ventricular heave and a grade 3/6 holosystolic heart murmur loudest at the upper left sternal border with radiation down the left sternal border toward the left mid-clavicular line. The lungs were clear to percussion and auscultation. There was moderate jugular venous distension without peripheral edema. There was RVH noted on the electrocardiogram, and cardiac enlargement noted on the cheat x-ray film without any pulmonary parenchymal abnormalities. A ventilation/perfusion lung scan gave normal findings. Echocardiogram showed a small left ventricle with a hypokinetic septum and decreued systolic function. reduced EF slope and an enlarged right ventricle. The patient underwent left and right heait catheterization. Right atrial ( RA) pressures ( mm Hg) were elevated 25, v 18 (mean RA-17); right ventricular to a pressures, 90/9; pulmonary artery pressures (PAP), 90/60 with a mean of 65. Aortic pressures were 140/80; left ventricular pressures (LVP), 140/80; mean pulmonary capillary wedge ( PCW), pressure 8. Peripheral pulmonary artery angiogram with hand injection demonstrated the "pruned tree" effect found with primary pulmonary hypertension. The patient failed to respond to a variety of therapeutic agents including 100 percent oxygen. 60 mg of tolazoline IV, 0.4 mg nitroglycerin SL, and prazosin 1 to 5 mg and hydralazine, 25 and 50 mg orally. The patient was re-admitted to the haspital on September 30, 1981. Results of the physical examination had changed from the previous admission with the development of marked jugular venous distention to the angle of the mandible while sitting upright, hepatomegaly with a span of 18 em in the right midclavicular line, a palpable splenic tip and 2+ pitting edema in the lower extremities extending to the mid thighs. The cardiac examination. electrocardiogram and chest x-ray film were unchanged. Radionuclide gated wall motion study showed a markedly enlarged

=

Table !--Summary of Hemod,--mie Re.po,..ea to (1•, Zrul and 4rl& Do..)

Nifedlpin.e 10 rq aJUI ZO rq

lOJIIIo

Control N 10mg

pulmonary hypertension may be caused by P rimary pulmonary vasocontriction. Attempts to alleviate 1

vasoconstriction have included the use of oxygen, acetylcholine, isoproterenol, phentolamine, diazoxide, tolazoline, prostacyclin, hydralazine, diltiazem, verapamil, and nifedipine. 2 • 8 We report a patient with primary pulmonary hypertension in whom nifedipine caused a dramatic reduction in pulmonary hypertension initially. However, tachyphylaxis developed with subsequent doses.

•From the Department of Medicine, Section of Cardiology, The Ben Taub General Haspital, Baylor College of Medicine, Houston. tPresently at Cork Regional Hospital, Wilton, Cork. Ire-

~~ requuta:

Howton 77030

=

Dr. Lucie. 1200 Mounund, Boom 512D,

PAP (iii) SBP RAPiD

HR PVR

75

72

26

63

64

120

102

70

68

90

19

15

17

09

24

118

115

107

105

116

34.8

%4 SVR

%4

N20mg N20mg N20mg 11 12 14

31.6 -9

55.8

44.7 -20

00.7 -69 28.9

-48

26.6 -23

27.5 -21

38.7

28.6

-48

-31

N -nifedipine; PAP-pulmonary artery pressure, m-mean; SBP-systolic blood pressure; RAP-right atrial pressure; HR- heart rate; PVR-pulmonary vascular resistance (IIi PAP+cardiac output); SVR-systemic vascular resistance (SBP+cardiac output) CHEST I 12 I 8 I DECEMBER, 1812

7U

right ventricle with global hypokinesis and a small normally contracting left ventricle. Right sided cardiac catheterization with a Swan-Ganz thermodilution catheter revealed the following pressures: RAP 12; PAP, 100/60 with a mean of 75; PCWP, 13; and a cardiac output of 2.7 liters per minute. The patient subsequently received in all seven doses of nifed.ipine, three of 10 mg and four of 20 mg. A summary of the hemodynamic effects of nifedipine after the first dose of 10 mg and following the first, second and fourth dose of 20 mg are tabulated in Table 1. After the administration of the first 20 mg dose of nifed.ipine, there was a marked reduction in PAP and pulmonary vascular resistance which, however, became progressively less with each subsequent dose of 20 mg. Following the first dose of nifedipine 20 mg, she became lightheaded and apprehensive, but administration of the subsequent doses of nifedipine was uneventful. Nifedipine also reduced the systemic vascular resistance, but in a dose-related manner with persistent drug effect aU doses. The reduction in PAP was not associated with a significant reduction in right atrial pressure eliminating a role for systemic venodilation alone in the etiology of the reduction in pulmonary vascular resistance. DISCUSSION

Nifedipine is a potent blocker of the slow inward calcium current and results in systemic vasodilatation and reflex beta adrenergic activity that blocks its potential negative inotropic, chronotropic and dromotropic effects. It has been found to lower the pulmonary artery pressure and pulmonary vascular resistance in a number of conditions, including congestive heart failure,T and hypoxic pulmonary vasoconstriction.8 Camerini and colleagues' have reported the successful use of nifedipine also in a case of primary pulmonary hypertension. Their patient responded acutely to the administration of the medication and showed a persistant ability to respond at the time of repeat hemodynamic evaluation after three months of treatment. The response of our patient to nifedipine was markedly different from that previously reported. She showed a modest reduction in systemic and pulmonary artery pressures after the first 10 mg dose. After nifedipine, 20 mg, however, she experienced a precipitous fall in her pulmonary artery pressure and reisistance and a lesser fall in systemic blood pressure and resistance. These effects lasted approximately three hours. In contrast to most other patients' reported responses to nifedipine, whether they had increased pulmonary artery pressures secondary to primary pulmonary hypertension or congestive heart failure, this patient did not increase her cardiac output or her heart rate concomitantly with her fall in systemic and pulmonary pressures. The reason for these differences in response is unclear. It is also noteworthy that the patient failed to show changes from baseline in her hemodynamics after further doses of 10 and 20 mg of nifedipine except for modest increases in her cardiac output. It was decided not to continue the patient on nifedipine because of the greater and excessive effect on systemic vascular resistance.

The results of this trial of nifedipine in the treatment of primary pulmonary hypertension appear to bear out the caveat of Camerini and colleagues' that "in primary pulmonary hypertension the response to this, as well as to other vasodilators, can be extremely variable from time to time and from one subject to another." The marked but transient reduction in pulmonary vascular resistance in this patient receiving nifedipine after failure of other agents may suggest a role for calcium antagonists in the treatment of some patients with primary pulmonary hypertension. Further observations are needed to confirm this clinical observation. ACKNOWLEDGMENTS: The authors wish to acknowledge the help of Ms. Carolyn Ferrante in the preparation of this manuscript.

REFERENCES 1 Wagenvoort CA, Wagenvoort N. Primary pulmonary hypertension. A pathologic study of the lungs in 156 clinically diagnosed cases. Circulation 1970; 42: 1163-84

2 Klinke WP. Treatment for primary pulmonary hypertension. Am Heart J 1980; 100:587-88 3 Guadagni DN, Ikram H, Maslowski AH. Haemodynamic effects of prostacyclin ( PGI.) in pulmonary hypertension. Br Heart J 1981; 45:385-88 4 Kambara H, Fujimoto K, Wakabayashi A, Kauri C. Primary pulmonary hypertension: beneficial therapy with diltiazem. Am Heart J 1981; 101 :230-31 5 Landmark K, Retsum AM, Simonsen S, Stordein 0. Verapamil and pulmonary hypertension. Acta Med Scand 1978; 20!:299-302 6 Camerini F, Alberti E, Klupmann S, Salir A. Primary

pulmonary hypertension: effects of nifed.ipine. Br Heart

J 1980; 44:352-56

7 Klugmann S, Palvi A, Camerini F. Haemodynamic effects of nifedipine in heart failure. Br Heart J 1980; 43:440-46 8 Simonneau G, Escourrou P, Duroux P, Lockhart A. Inhibition of hypoxic pulmonary vasoconstriction by nifedipine. N Engl J Med 1981; 304:1582-86

Disappearance of Exercise-Induced ST-Segment Depression Associated with Transient Left Anterior Hemiblock* Milch T.C. Huang, M.D.;t and Puthenpuralcal K. Mathew, M.D., F.C.C.P.

To our knowledge, tbfs Is the first case reported of total disappeal'llllee of eserdse-laduced ST«p~eat depre. sloa Ia the pnseac:e of traasieat left aatertor bemiltlock at peak eseadie. Aa aa1111181 paradoxic IDcrease Ia Twave amplitade also aotlced. The slplficaat STsep~eat displacemeat reappeared whea the traasleat

w•

•From the Cardiology Unit, St. Mary's Hospital, and Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York. tPresently Chie£1 Section of Cardiology, Veterans Administration Medical Center, Canadaigua. New York. &print requem: Dr. Hutlfll{, Chlef, Section of Cardlolollfl, VA Medical Center, Ct~t&QtKtatgua, New York 14424

DIMPPM1'8110• of ExerciM-Induced ST-eegment Depre..lon (HUallfl, Mathew)