Failure of calcium channel blockers to improve ventricular relaxation in humans. 1993

R A Nishimura, and R S Schwartz, and D R Holmes, and A J Tajik
Division of Cardiovascular Diseases and Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905.

OBJECTIVE The objective of this study was to ascertain whether the reversal of low peak filling rates after administration of calcium channel blockers in patients with diastolic dysfunction indicates true improvement in the rate of ventricular relaxation and left ventricular end-diastolic pressure measured by invasive indexes. BACKGROUND Depressed filling rates measured noninvasively have been associated with diastolic dysfunction, specifically abnormal relaxation of the left ventricle. There is a reversal of these low peak filling rates after administration of calcium channel blockers. METHODS Doppler echocardiographic measurements of peak filling rates were made and invasive high fidelity manometer-tipped pressures were measured before and after administration of verapamil (0.1 mg/kg body weight) in 20 patients with coronary artery disease who had an ejection fraction > 40% and decreased peak filling rates. RESULTS Verapamil caused significant increases in the peak filling rate, as measured by early transmitral (E) flow velocity, from 0.57 +/- 0.16 m/s to 0.77 +/- 0.15 m/s (p < 0.01), indicating reversal of decreased peak filling rates. Concomitantly, left ventricular end-diastolic pressure increased from 18.0 +/- 7.7 mm Hg to 24.1 +/- 9.0 mm Hg (p < 0.001). The time constant of relaxation was variable, with an overall significant increase from 45.8 +/- 10.4 ms to 53.2 +/- 14.6 ms (p = 0.01). CONCLUSIONS Verapamil administered intravenously produced reversal of decreased peak filling rates in patients with coronary artery disease and normal ventricular function. However, there was an increase in left ventricular end-diastolic pressure as well as an overall prolongation of the time constant of relaxation. Therefore, changes in peak filling rates do not accurately reflect the response of ventricular relaxation to drug interactions. Thus, calcium channel blockers should be used cautiously in the empiric treatment of patients with diastolic dysfunction.

UI MeSH Term Description Entries
D008297 Male Males
D008875 Middle Aged An adult aged 45 - 64 years. Middle Age
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D011446 Prospective Studies Observation of a population for a sufficient number of persons over a sufficient number of years to generate incidence or mortality rates subsequent to the selection of the study group. Prospective Study,Studies, Prospective,Study, Prospective
D012044 Regression Analysis Procedures for finding the mathematical function which best describes the relationship between a dependent variable and one or more independent variables. In linear regression (see LINEAR MODELS) the relationship is constrained to be a straight line and LEAST-SQUARES ANALYSIS is used to determine the best fit. In logistic regression (see LOGISTIC MODELS) the dependent variable is qualitative rather than continuously variable and LIKELIHOOD FUNCTIONS are used to find the best relationship. In multiple regression, the dependent variable is considered to depend on more than a single independent variable. Regression Diagnostics,Statistical Regression,Analysis, Regression,Analyses, Regression,Diagnostics, Regression,Regression Analyses,Regression, Statistical,Regressions, Statistical,Statistical Regressions
D002121 Calcium Channel Blockers A class of drugs that act by selective inhibition of calcium influx through cellular membranes. Calcium Antagonists, Exogenous,Calcium Blockaders, Exogenous,Calcium Channel Antagonist,Calcium Channel Blocker,Calcium Channel Blocking Drug,Calcium Inhibitors, Exogenous,Channel Blockers, Calcium,Exogenous Calcium Blockader,Exogenous Calcium Inhibitor,Calcium Channel Antagonists,Calcium Channel Blocking Drugs,Exogenous Calcium Antagonists,Exogenous Calcium Blockaders,Exogenous Calcium Inhibitors,Antagonist, Calcium Channel,Antagonists, Calcium Channel,Antagonists, Exogenous Calcium,Blockader, Exogenous Calcium,Blocker, Calcium Channel,Blockers, Calcium Channel,Calcium Blockader, Exogenous,Calcium Inhibitor, Exogenous,Channel Antagonist, Calcium,Channel Blocker, Calcium,Inhibitor, Exogenous Calcium
D003327 Coronary Disease An imbalance between myocardial functional requirements and the capacity of the CORONARY VESSELS to supply sufficient blood flow. It is a form of MYOCARDIAL ISCHEMIA (insufficient blood supply to the heart muscle) caused by a decreased capacity of the coronary vessels. Coronary Heart Disease,Coronary Diseases,Coronary Heart Diseases,Disease, Coronary,Disease, Coronary Heart,Diseases, Coronary,Diseases, Coronary Heart,Heart Disease, Coronary,Heart Diseases, Coronary
D003971 Diastole Post-systolic relaxation of the HEART, especially the HEART VENTRICLES. Diastoles
D005260 Female Females
D006328 Cardiac Catheterization Procedures in which placement of CARDIAC CATHETERS is performed for therapeutic or diagnostic procedures. Catheterization, Cardiac,Catheterization, Heart,Heart Catheterization,Cardiac Catheterizations,Catheterizations, Cardiac,Catheterizations, Heart,Heart Catheterizations

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