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. 1997 Jan;77(1):32–39. doi: 10.1136/hrt.77.1.32

Impaired left ventricular filling dynamics in patients with angina and angiographically normal coronary arteries: effect of beta adrenergic blockade.

G Fragasso 1, S L Chierchia 1, G Pizzetti 1, E Rossetti 1, M Carlino 1, S Gerosa 1, O Carandente 1, A Fedele 1, N Cattaneo 1
PMCID: PMC484631  PMID: 9038691

Abstract

OBJECTIVE: To assess exercise performance and resting left ventricular filling dynamics in patients with syndrome X (SX) in basal conditions and after 10 days treatment with oral atenolol. DESIGN AND PATIENTS: Exercise performance was studied and left ventricular filling assessed by Doppler-derived transmitral flow pattern analysis in 22 patients (16 female, mean (SD) age 53 (4) years) with angina, a positive exercise test, and angiographically smooth coronary arteries. Patients were studied after two 10 day treatment periods with either atenolol or placebo in a single-blind, randomised, crossover trial. The same protocol was followed in 10 patients with documented coronary artery disease (CAD) and in 13 controls (C). RESULTS: Unlike the controls, patients with SX and those with CAD consistently showed exercise-induced ST segment abnormalities and impaired resting left ventricular filling while on placebo. Atenolol significantly reduced episodes of angina, completely prevented exercise-induced ST segment changes in 18 SX patients, and delayed their onset in all patients with CAD: in both groups the agent significantly improved Doppler-derived indices (mean (SD)) of ventricular filling (E/A 0.97 (0.27) v 1.22 (0.32) and 0.84 (0.21) v 1.19 (0.37), respectively). CONCLUSIONS: The objective documentation of left ventricular filling abnormalities may be useful in confirming the clinical diagnosis of SX and in providing objective evidence of therapeutic benefit. The similarity of the symptoms and electrocardiographic and ventricular filling abnormalities found in patients with SX and in those with CAD suggests that ischaemia is involved in both groups.

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Selected References

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  1. Arbogast R., Bourassa M. G. Myocardial function during atrial pacing in patients with angina pectoris and normal coronary arteriograms. Comparison with patients having significant coronary artery disease. Am J Cardiol. 1973 Sep 7;32(3):257–263. doi: 10.1016/s0002-9149(73)80130-4. [DOI] [PubMed] [Google Scholar]
  2. Bonow R. O., Bacharach S. L., Green M. V., Kent K. M., Rosing D. R., Lipson L. C., Leon M. B., Epstein S. E. Impaired left ventricular diastolic filling in patients with coronary artery disease: assessment with radionuclide angiography. Circulation. 1981 Aug;64(2):315–323. doi: 10.1161/01.cir.64.2.315. [DOI] [PubMed] [Google Scholar]
  3. Bristow J. D., Van Zee B. E., Judkins M. P. Systolic and diastolic abnormalities of the left ventricle in coronary artery disease. Studies in patients with little or no enlargement of ventricular volume. Circulation. 1970 Aug;42(2):219–228. doi: 10.1161/01.cir.42.2.219. [DOI] [PubMed] [Google Scholar]
  4. Brown B. G., Lee A. B., Bolson E. L., Dodge H. T. Reflex constriction of significant coronary stenosis as a mechanism contributing to ischemic left ventricular dysfunction during isometric exercise. Circulation. 1984 Jul;70(1):18–24. doi: 10.1161/01.cir.70.1.18. [DOI] [PubMed] [Google Scholar]
  5. Bugiardini R., Borghi A., Biagetti L., Puddu P. Comparison of verapamil versus propranolol therapy in syndrome X. Am J Cardiol. 1989 Feb 1;63(5):286–290. doi: 10.1016/0002-9149(89)90332-9. [DOI] [PubMed] [Google Scholar]
  6. Cannon R. O., 3rd, Bonow R. O., Bacharach S. L., Green M. V., Rosing D. R., Leon M. B., Watson R. M., Epstein S. E. Left ventricular dysfunction in patients with angina pectoris, normal epicardial coronary arteries, and abnormal vasodilator reserve. Circulation. 1985 Feb;71(2):218–226. doi: 10.1161/01.cir.71.2.218. [DOI] [PubMed] [Google Scholar]
  7. Cannon R. O., 3rd, Watson R. M., Rosing D. R., Epstein S. E. Angina caused by reduced vasodilator reserve of the small coronary arteries. J Am Coll Cardiol. 1983 Jun;1(6):1359–1373. doi: 10.1016/s0735-1097(83)80037-0. [DOI] [PubMed] [Google Scholar]
  8. Carroll J. D., Hess O. M., Hirzel H. O., Krayenbuehl H. P. Dynamics of left ventricular filling at rest and during exercise. Circulation. 1983 Jul;68(1):59–67. doi: 10.1161/01.cir.68.1.59. [DOI] [PubMed] [Google Scholar]
  9. Chierchia S., Gerosa S., Glazier J. J. Beta-blockers for the treatment of angina pectoris: indications in relation to pathophysiological mechanisms. J Cardiovasc Pharmacol. 1987;10 (Suppl 2):S29–S33. [PubMed] [Google Scholar]
  10. Chierchia S., Muiesan L., Davies A., Balasubramian V., Gerosa S., Raftery E. B. Role of the sympathetic nervous system in the pathogenesis of chronic stable angina. Implications for the mechanism of action of beta-blockers. Circulation. 1990 Sep;82(3 Suppl):II71–II81. [PubMed] [Google Scholar]
  11. Devereux R. B., Reichek N. Echocardiographic determination of left ventricular mass in man. Anatomic validation of the method. Circulation. 1977 Apr;55(4):613–618. doi: 10.1161/01.cir.55.4.613. [DOI] [PubMed] [Google Scholar]
  12. Diamond G., Forrester J. S. Effect of coronary artery disease and acute myocardial infarction on left ventricular compliance in man. Circulation. 1972 Jan;45(1):11–19. doi: 10.1161/01.cir.45.1.11. [DOI] [PubMed] [Google Scholar]
  13. Dwyer E. M., Jr, Wiener L., Cox J. W. Angina pectoris in patients with normal and abnormal coronary arteriograms. Am J Cardiol. 1969 May;23(5):639–646. doi: 10.1016/0002-9149(69)90024-1. [DOI] [PubMed] [Google Scholar]
  14. Egashira K., Inou T., Hirooka Y., Yamada A., Urabe Y., Takeshita A. Evidence of impaired endothelium-dependent coronary vasodilatation in patients with angina pectoris and normal coronary angiograms. N Engl J Med. 1993 Jun 10;328(23):1659–1664. doi: 10.1056/NEJM199306103282302. [DOI] [PubMed] [Google Scholar]
  15. Favaro L., Caplin J. L., Fettiche J. J., Dymond D. S. Sex differences in exercise induced left ventricular dysfunction in patients with syndrome X. Br Heart J. 1987 Mar;57(3):232–236. doi: 10.1136/hrt.57.3.232. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Fragasso G., Benti R., Sciammarella M., Rossetti E., Savi A., Gerundini P., Chierchia S. L. Symptom-limited exercise testing causes sustained diastolic dysfunction in patients with coronary disease and low effort tolerance. J Am Coll Cardiol. 1991 May;17(6):1251–1255. doi: 10.1016/s0735-1097(10)80131-7. [DOI] [PubMed] [Google Scholar]
  17. Frist W. H., Palacios I., Powell W. J., Jr Effect of hypoxia on myocardial relaxation in isometric cat papillary muscle. J Clin Invest. 1978 May;61(5):1218–1224. doi: 10.1172/JCI109037. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gaasch W. H., Levine H. J., Quinones M. A., Alexander J. K. Left ventricular compliance: mechanisms and clinical implications. Am J Cardiol. 1976 Nov 4;38(5):645–653. doi: 10.1016/s0002-9149(76)80015-x. [DOI] [PubMed] [Google Scholar]
  19. Gibbons R. J., Lee K. L., Cobb F., Jones R. H. Ejection fraction response to exercise in patients with chest pain and normal coronary arteriograms. Circulation. 1981 Nov;64(5):952–957. doi: 10.1161/01.cir.64.5.952. [DOI] [PubMed] [Google Scholar]
  20. Gibson D. G., Prewitt T. A., Brown D. J. Analysis of left ventricular wall movement during isovolumic relaxation and its relation to coronary artery disease. Br Heart J. 1976 Oct;38(10):1010–1019. doi: 10.1136/hrt.38.10.1010. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Grossman W., McLaurin L. P. Diastolic properties of the left ventricle. Ann Intern Med. 1976 Mar;84(3):316–326. doi: 10.7326/0003-4819-84-3-316. [DOI] [PubMed] [Google Scholar]
  22. Heusch G., Deussen A. The effects of cardiac sympathetic nerve stimulation on perfusion of stenotic coronary arteries in the dog. Circ Res. 1983 Jul;53(1):8–15. doi: 10.1161/01.res.53.1.8. [DOI] [PubMed] [Google Scholar]
  23. Heyndrickx G. R., Millard R. W., McRitchie R. J., Maroko P. R., Vatner S. F. Regional myocardial functional and electrophysiological alterations after brief coronary artery occlusion in conscious dogs. J Clin Invest. 1975 Oct;56(4):978–985. doi: 10.1172/JCI108178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kemp H. G., Jr Left ventricular function in patients with the anginal syndrome and normal coronary arteriograms. Am J Cardiol. 1973 Sep 7;32(3):375–376. doi: 10.1016/s0002-9149(73)80150-x. [DOI] [PubMed] [Google Scholar]
  25. Mammohansingh P., Parker J. O. Angina pectoris with normal coronary arteriograms: hemodynamic and metabolic response to atrial pacing. Am Heart J. 1975 Nov;90(5):555–561. doi: 10.1016/0002-8703(75)90217-3. [DOI] [PubMed] [Google Scholar]
  26. Mann T., Goldberg S., Mudge G. H., Jr, Grossman W. Factors contributing to altered left ventricular diastolic properties during angina pectoris. Circulation. 1979 Jan;59(1):14–20. doi: 10.1161/01.cir.59.1.14. [DOI] [PubMed] [Google Scholar]
  27. McLaurin L. P., Rolett E. L., Grossman W. Impaired left ventricular relaxation during pacing-induced ischemia. Am J Cardiol. 1973 Nov;32(6):751–757. doi: 10.1016/s0002-9149(73)80002-5. [DOI] [PubMed] [Google Scholar]
  28. Mirsky I., Cohn P. F., Levine J. A., Gorlin R., Herman M. V., Kreulen T. H., Sonnenblick E. H. Assessment of left ventricular stiffness in primary myocardial disease and coronary artery disease. Circulation. 1974 Jul;50(1):128–136. doi: 10.1161/01.cir.50.1.128. [DOI] [PubMed] [Google Scholar]
  29. Montorsi P., Fabbiocchi F., Loaldi A., Annoni L., Polese A., De Cesare N., Guazzi M. D. Coronary adrenergic hyperreactivity in patients with syndrome X and abnormal electrocardiogram at rest. Am J Cardiol. 1991 Dec 15;68(17):1698–1703. doi: 10.1016/0002-9149(91)90332-f. [DOI] [PubMed] [Google Scholar]
  30. Motz W., Vogt M., Rabenau O., Scheler S., Lückhoff A., Strauer B. E. Evidence of endothelial dysfunction in coronary resistance vessels in patients with angina pectoris and normal coronary angiograms. Am J Cardiol. 1991 Oct 15;68(10):996–1003. doi: 10.1016/0002-9149(91)90485-4. [DOI] [PubMed] [Google Scholar]
  31. Nihoyannopoulos P., Kaski J. C., Crake T., Maseri A. Absence of myocardial dysfunction during stress in patients with syndrome X. J Am Coll Cardiol. 1991 Nov 15;18(6):1463–1470. doi: 10.1016/0735-1097(91)90676-z. [DOI] [PubMed] [Google Scholar]
  32. Nixon J. V., Wright A. R., Porter T. R., Roy V., Arrowood J. A. Effects of exercise on left ventricular diastolic performance in trained athletes. Am J Cardiol. 1991 Oct 1;68(9):945–949. doi: 10.1016/0002-9149(91)90414-g. [DOI] [PubMed] [Google Scholar]
  33. Opherk D., Zebe H., Weihe E., Mall G., Dürr C., Gravert B., Mehmel H. C., Schwarz F., Kübler W. Reduced coronary dilatory capacity and ultrastructural changes of the myocardium in patients with angina pectoris but normal coronary arteriograms. Circulation. 1981 Apr;63(4):817–825. doi: 10.1161/01.cir.63.4.817. [DOI] [PubMed] [Google Scholar]
  34. Paulus W. J., Serizawa T., Grossman W. Altered left ventricular diastolic properties during pacing-induced ischemia in dogs with coronary stenoses. Potentiation by caffeine. Circ Res. 1982 Feb;50(2):218–227. doi: 10.1161/01.res.50.2.218. [DOI] [PubMed] [Google Scholar]
  35. Phillips R. A., Goldman M. E., Ardeljan M., Arora R., Eison H. B., Yu B. Y., Krakoff L. R. Determinants of abnormal left ventricular filling in early hypertension. J Am Coll Cardiol. 1989 Oct;14(4):979–985. doi: 10.1016/0735-1097(89)90476-2. [DOI] [PubMed] [Google Scholar]
  36. Presti C. F., Walling A. D., Montemayor I., Campbell J. M., Crawford M. H. Influence of exercise-induced myocardial ischemia on the pattern of left ventricular diastolic filling: a Doppler echocardiographic study. J Am Coll Cardiol. 1991 Jul;18(1):75–82. doi: 10.1016/s0735-1097(10)80221-9. [DOI] [PubMed] [Google Scholar]
  37. Romeo F., Gaspardone A., Ciavolella M., Gioffrè P., Reale A. Verapamil versus acebutolol for syndrome X. Am J Cardiol. 1988 Aug 1;62(4):312–313. doi: 10.1016/0002-9149(88)90232-9. [DOI] [PubMed] [Google Scholar]
  38. Schofield P. M., Brooks N. H., Bennett D. H. Left ventricular dysfunction in patients with angina pectoris and normal coronary angiograms. Br Heart J. 1986 Oct;56(4):327–333. doi: 10.1136/hrt.56.4.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Schofield P. M., Brooks N. H., Colgan S., Bennett D. H., Whorwell P. J., Bray C. L., Ward C., Jones P. E. Left ventricular function and oesophageal function in patients with angina pectoris and normal coronary angiograms. Br Heart J. 1987 Sep;58(3):218–224. doi: 10.1136/hrt.58.3.218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Smith S. A., Stoner J. E., Russell A. E., Sheppard J. M., Aylward P. E. Transmitral velocities measured by pulsed Doppler in healthy volunteers: effects of acute changes in blood pressure and heart rate. Br Heart J. 1989 Apr;61(4):344–347. doi: 10.1136/hrt.61.4.344. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Spirito P., Maron B. J. Relation between extent of left ventricular hypertrophy and diastolic filling abnormalities in hypertrophic cardiomyopathy. J Am Coll Cardiol. 1990 Mar 15;15(4):808–813. doi: 10.1016/0735-1097(90)90278-w. [DOI] [PubMed] [Google Scholar]
  42. Störk T. V., Möckel M., Eichstädt H., Müller R. M., Hochrein H. Noninvasive assessment by pulsed Doppler ultrasound of left ventricular filling behavior in long distance runners during marathon race. Am J Cardiol. 1991 Nov 1;68(11):1237–1241. doi: 10.1016/0002-9149(91)90203-w. [DOI] [PubMed] [Google Scholar]
  43. Teichholz L. E., Kreulen T., Herman M. V., Gorlin R. Problems in echocardiographic volume determinations: echocardiographic-angiographic correlations in the presence of absence of asynergy. Am J Cardiol. 1976 Jan;37(1):7–11. doi: 10.1016/0002-9149(76)90491-4. [DOI] [PubMed] [Google Scholar]
  44. Verdecchia P., Schillaci G., Guerrieri M., Boldrini F., Gatteschi C., Benemio G., Porcellati C. Prevalence and determinants of left ventricular diastolic filling abnormalities in an unselected hypertensive population. Eur Heart J. 1990 Aug;11(8):679–691. doi: 10.1093/oxfordjournals.eurheartj.a059783. [DOI] [PubMed] [Google Scholar]
  45. Vrints C. J., Bult H., Hitter E., Herman A. G., Snoeck J. P. Impaired endothelium-dependent cholinergic coronary vasodilation in patients with angina and normal coronary arteriograms. J Am Coll Cardiol. 1992 Jan;19(1):21–31. doi: 10.1016/0735-1097(92)90046-p. [DOI] [PubMed] [Google Scholar]

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