Brian G. Firth

Limitations of qualitative angiographic grading in aortic or mitral regurgitation

This study was performed to assess the accuracy of qualitative angiographic grading in persons with aortic regurgitation (AR) or mitral regurgitation (MR) and to determine the factors that may influence the reliability of such grading. In 230 patients (152 men, 78 women, aged 52 +/- 14 years) with AR or MR, forward cardiac index was measured by the Fick and indicator dilution techniques and left ventricular (LV) angiographic index by the area-length method, from which the regurgitant volume index was calculated. In 124 other patients (89 men, 35 women, aged 52 +/- 11 years) without regurgitation, there was good agreement between forward and angiographic cardiac indexes (r = 0.87, p less than 0.001). In the 83 patients with AR, the regurgitant volume indexes in those with 1+ (0.87 +/- 0.57 liters/min/m2) and 2+ (1.72 +/- 1.19 liters/min/m2) angiographic regurgitation were not significantly different from one another, but were significantly different from those with 3+ (3.0 +/- 1.42 liters/min/m2) and 4+ (4.80 +/- 2.25 liters/min/m2) regurgitation; at the same time, the regurgitant volume indexes of patients with 3+ and 4+ AR were not significantly different from one another. In the 147 patients with MR, the regurgitant volume indexes in patients with 1+ regurgitation (0.61 +/- 0.64 liters/min/m2) were significantly lower than other grades, but the regurgitant volume indexes of 2+ (1.14 +/- 0.85 liters/min/m2) vs 3+ (2.14 +/- 1.37 liters/min/m2) and of 3+ vs 4+ (4.60 +/- 2.31 liters/min/m2) were not significantly different. With AR and MR, regurgitant flow within each angiographic grade varied widely, especially in grades 3+ and 4+, and there was considerable overlap of regurgitant volume indexes between grades.(ABSTRACT TRUNCATED AT 250 WORDS)

Continuous electrocardiographic monitoring in patients with unstable angina pectoris: Identification of high-risk subgroup with severe coronary disease, variant angina, and/or impaired early prognosis

We assessed the value of two-channel Holter monitoring during the initial hours of hospitalization in patients with unstable angina pectoris (UAP) to identify those with severe coronary artery disease (CAD), variant angina, and/or poor prognosis over the next 3 months. Accordingly, 116 UAP patients had Holter monitoring for 27 +/- 7 (mean +/- SD) (range 12 to 50) hours following hospitalization. Of these, 24 evolved myocardial infarction (MI) during monitoring and 92 did not. Transient ST segment alterations occurred in 21 of the 92. Of these 21, 4 had variant angina, were treated with calcium antagonists, and did well. Each of the remaining 17 had severe fixed CAD (left main or three-vessel) (n = 12) and/or poor prognosis over the 3 months after discharge as manifested by death (n = 1), MI (n = 3), and/or severe angina (n = 3). In contrast, 71 patients did not demonstrate transient ST segment alterations: none had variant angina (p less than 0.001), nine had left main or three-vessel CAD (p less than 0.001), and 50 were alive and well 3 months after discharge (p less than 0.001). Ventricular tachycardia (VT) was demonstrated by Holter monitor in 5 of the 92 patients: four had three-vessel CAD and the other had severe persistent angina. Thus in patients hospitalized with unstable angina, transient ST segment alterations and/or VT on Holter monitor are specific predictors of high-risk subgroup UAP patients with left main or three-vessel CAD, variant angina, and/or impaired 3-month prognosis.

Efficacy of prazosin in the management of chronic congestive heart failure: A 6-month randomized, double-blind, placebo-controlled study

The beneficial effects of acute prazosin therapy in patients with congestive heart failure (CHF) have been well documented; however, its chronic efficacy over several months has not previously been evaluated in a placebo-controlled manner. Therefore, an assessment was made by radionuclide ventriculography of the effect of prazosin, 20 mg/day, on left ventricular ejection fraction and end-systolic and end-diastolic volumes at rest and on peak upright bicycle exercise, as well as its effect on right ventricular ejection fraction at rest, exercise time and work load, and standard clinical variables in 23 patients with stable class III symptoms of CHF. The study consisted of a 6-month randomized, double-blind, controlled evaluation of prazosin versus placebo in patients receiving a stable dose of digitalis and diuretics for at least 1 month. At entry, the prazosin and placebo groups did not differ in any respect. Prazosin caused no demonstrable effect on clinical variables such as status of symptoms, heart rate, mean arterial pressure, and cardiothoracic ratio when compared with placebo. Prazosin also caused no demonstrable effect compared with placebo on absolute or percent changes in radionuclide variables at rest or on peak exercise, or on exercise time or exercise work load. In addition, prazosin had no consistent effect compared with placebo on plasma renin activity or plasma catecholamine levels. However, there was a slight but significant increase in weight (p less than 0.0001) and in plasma renin activity in the upright position (p less than 0.002) with time, as well as a tendency for the diuretic dose to increase with time in both groups. Thus, long-term prazosin therapy generally produces no demonstrable subjective or objective improvement in patients with stable, chronic class III CHF receiving digitalis and diuretic therapy.

Hemodynamic and electrophysiologic effects of verapamil and nifedipine in patients on propranolol

Abstract Because the combined use of a beta-adrenergic blocking agent and a calcium antagonist may be beneficial in patients with severe angina, we assessed the hemodynamic and electrophysiologic effects of verapamil or nifedipine in patients receiving oral propranolol. In 26 patients with stable angina receiving oral propranolol (234 ± 230 mg/day, mean ± standard deviation), cardiac catheterization was performed, and variables were measured at baseline and 5 to 10 minutes after (1) intravenous saline solution, 10 ml (n = 6); (2) intravenous verapamil, 0.15 mg/kg body weight to a maximal dose of 10 mg (n = 10); and (3) sublingual nifedipine, 10 mg (n = 10). Cardiac output (by thermodilution) was unchanged after saline solution and verapamil but increased with nifedipine (4.3 ± 1.1 to 5.0 ± 1.4 liters/min, p

Direct measurement of cardiac output by gated equilibrium blood pool scintigraphy: Validation of scintigraphic volume measurements by a nongeometric technique

Abstract A nongeometric technique for the determination of left ventricular volumes from the count data derived from gated equilibrium blood pool scans was previously described and validated by the demonstration of an excellent correlation between the derived data and angiographically determined left ventricular volumes. To provide a further prospective evaluation of this method and to validate its ability to determine stroke volume and cardiac output by a technique that is itself independent of geometric assumptions, simultaneous measurements of cardiac output by the thermodilution technique and gated scintigraphy were performed in 21 patients without valve regurgitation or intracardiac shunts. To substantiate the reliability of scintigraphic measurements at high levels of cardiac output, seven patients had multiple measurements of cardiac output at rest and during an infusion of isoproterenol. There was an excellent correlation between thermodilution and scintigraphic values for cardiac output (scan cardiac output = 0.99 thermodilution cardiac output − 0.005 liters/min; n = 31, standard error of the estimate [SEE]= 0.175 liters/min, r = 0.97) as well as between thermodilution and scintigraphic stroke volumes (scan stroke volume = 1.03 thermodilution stroke volume − 2.8 ml; n = 31, SEE = 2.5 ml, r = 0.95). In addition, the relation between scintigraphic and angiographic measurements of left ventricular volumes continued to be excellent: In 15 patients with technically adequate angiograms, scintigraphic left ventricular volume = 0.90 angiographic left ventricular volume + 7 ml (n = 30, SEE = 10 ml, r = 0.91). Thus, this study further validates the nongeometric method of measuring left ventricular volumes with gated scintigraphy and demonstrates its ability to measure left ventricular stroke volume and cardiac output reliably.

Symptomatic, electrocardiographic, metabolic, and hemodynamic alterations during pacing-induced myocardial ischemia

Atrial pacing has been used to assess the physiologic impact of coronary artery disease (CAD). Several variables have served as markers of pacing-induced myocardial ischemia, but their specificities and sensitivities are unknown. Accordingly, in 28 patients, incremental atrial pacing was performed. Of the 28, 10 had no CAD. The left ventricular ejection fraction (LVEF) (by gated equilibrium blood pool scintigraphy) increased in this group (0.60 +/- 0.11 [mean +/- standard deviation] before pacing to 0.67 +/- 0.13 at peak-pacing, p = 0.002). In no patient did left ventricular end-diastolic pressure increase by greater than 5 mm Hg. No patient had lactate production, and 2 (20%) had electrocardiographic S-T segment depression greater than or equal to 0.1 mV. Four (40%) had chest pain with atrial pacing. In the remaining 18 patients with CAD, atrial pacing caused a decrease in LVEF greater than or equal to 0.05 (0.46 +/- 0.10 to 0.33 +/- 0.09, p less than 0.001) and new segmental wall motion abnormalities in all, indicating pacing-induced myocardial ischemia. Only 8 (44%) had an increase in left ventricular end-diastolic pressure of greater than 5 mm Hg, and only 9 (50%) had lactate production. Ten (56%) had ischemic electrocardiographic changes, and 12 (67%) had chest pain. Thus, the electrocardiographic, metabolic, and hemodynamic alterations that may accompany pacing-induced ischemia are specific but relatively insensitive markers of ischemia. In contrast, chest pain during atrial pacing is a nonspecific occurrence, appearing with similar frequency in normal subjects and patients with CAD and pacing-induced ischemia.

Prognostic value of resting and submaximal exercise radionuclide ventriculography after acute myocardial infarction in high-risk patients with single and multivessel disease

In patients who survive the acute phase of myocardial infarction, those with multivessel coronary artery disease generally have a worse prognosis than those with single-vessel disease. However, some patients with significant multivessel stenoses have a good prognosis, whereas some with a significant single-vessel stenosis have a poor prognosis. Thus, although definition of coronary anatomy may be helpful, it is a not a fail-safe prognosticator. In this retrospective analysis, the association of abnormalities at rest and during submaximal exercise testing with radionuclide ventriculography after acute myocardial infarction with major cardiac complications (death, recurrent infarction, severe angina or congestive heart failure) in the ensuing 6 months was assessed in patients with single and multivessel disease. Coronary angiography and submaximal exercise testing with radionuclide ventriculography were performed within 3 months of each other in 42 patients. Eleven of the 16 patients with single-vessel coronary stenosis had major cardiac complications. The subsequent course of these 16 patients was correctly predicted by left ventricular ejection fraction (LVEF) less than or equal to 0.40 in 8 patients, by LVEF less than 0.55 in 7 patients, by failure of LVEF to increase by 0.05 units in 13 patients, and by an increase in left ventricular end-systolic volume index (LVESVI) during exercise greater than 5% above baseline in 11 patients. Of the 26 patients with multivessel coronary artery disease, 24 had major cardiac complications. The subsequent course of these 26 patients was correctly predicted in 13 by LVEF less than or equal to 0.40, in 20 by LVEF less than 0.55, in 25 by a failure of LVEF to increase by 0.05 units during exercise, and in 20 by an increase in LVESVI by greater than 5% during exercise. Thus, submaximal exercise testing with radionuclide ventriculography may provide valuable prognostic information concerning the occurrence of major cardiac events after myocardial infarction not only in patients with multivessel disease, but also in those with single-vessel disease. Exercise-induced abnormalities of left ventricular function may have greater prognostic importance than the delineation of coronary arterial anatomy or the assessment of residual left ventricular function at rest.

Early detection of left ventricular dysfunction in chronic aortic regurgitation as assessed by contrast angiography, echocardiography, and rest and exercise scintigraphy

Abstract The best method for detecting early left ventricular (LV) dysfunction in patients with chronic aortic regurgitation is uncertain. Variables used previously to identify LV dysfunction have included (1) angiographic measurements to identify an LV end-systolic volume index (LVESVI) ≥60 ml/m 2 , (2) echocardiographic measurements to identify LV end-systolic dimension (LVESD) ≥5.5 cm or LV fractional shortening ≤25%, and (3) depressed LV ejection fraction (EF) at rest and/or an LVEF or LVESVI that deteriorates with exercise as detected by myocardial scintigraphic measurements. The hypothesis was tested that radionuclide ventriculography with exercise allows earlier detection of important LV dysfunction in patients with aortic regurgitation than the other variables. In 15 consecutive asymptomatic or only minimally symptomatic patients (8 men and 7 women, mean age 44 years) with isolated 2 to 4+ aortic regurgitation (1) rest and exercise-gated radionuclide ventriculography, (2) M-mode echocardiography, and (3) LV angiography were performed. No other cause of LV dysfunction was apparent in 13 patients; 1 patient had moderate systemic arterial hypertension and 1 had 50% luminal diameter narrowing of the proximal left anterior descending coronary artery. Ten patients did not have an increase in LVEF >0.05 EF units at peak exercise (0.58 ± 0.11 to 0.50 ± 0.12, mean ± standard deviation [SD]) (Group 2), whereas 5 had a normal LVEF response to exercise (0.63 ± 0.08 to 0.69 ± 0.07) (Group 1). Eight of the 10 patients with abnormal LVEF responses to exercise had a decrease in LVEF >10% during exercise. The same 8 patients also had an increase in LVESVI with exercise, whereas the 5 patients with normal LVEF responses to exercise had normal or blunted LVESVI responses to exercise. Only 4 of the 10 patients with exercise-induced LV dysfunction had an angiographic LVESVI ≥60 ml/m 2 , and only 1 had an echocardiographically determined LVESD ≥5.5 cm. Serial follow-up rest and exercise scintigraphic and echocardiographic measurements were made in 8 of the patients a mean of 9.4 months after the initial measurements; 3 patients were in Group 1 and 5 in Group 2. The 5 patients in Group 2 again demonstated abnormal LV function during exercise stress, and 2 of the 3 patients in Group 1 then demonstrated an abnormal LV functional response during exercise. Therefore, it is concluded that (1) exercise radionuclide ventriculography identifies LV dysfunction earlier than traditionally used assessments, (2) LV dysfunction appears to persist in patients that demonstrate it and develop in others that did not have it originally, and (3) echocardiographic dilatation of the LVESD to 5.5 cm appears to be a late and relatively unusual occurrence.

Assessment of the inotropic and vasodilator effects of amrinone versus isoproterenol

The hemodynamic effects of graded-dose infusions of amrinone (maximal dose 30 micrograms/kg/min) (10 patients) and isoproterenol (maximum dose 4 micrograms/min) (11 patients) were assessed in patients with a range of left ventricular (LV) function. LV ejection fraction ranged from 0.13 to 0.77 (mean +/- standard deviation 0.47 +/- 0.23) among the patients who received amrinone and from 0.24 to 0.77 (mean 0.52 +/- 0.18) among those who received isoproterenol. Peak-dose amrinone produced a reduction in LV filling pressure (from 15 +/- 10 to 10 +/- 7 mm Hg, p less than 0.001), but no significant change in heart rate, cardiac output, mean aortic pressure, total systemic vascular resistance (TSVR) or LV dP/dt max. In contrast, peak-dose isoproterenol produced a similar reduction in LV filling pressure (from 17 +/- 12 to 13 +/- 13 mm Hg, p less than 0.05), but also caused increases in heart rate, cardiac output and LV dP/dt max and decreases in mean aortic pressure and TSVR (p less than 0.001). The absolute change in cardiac output and stroke volume correlated closely with the change in TSVR in response to amrinone (r = -0.90, p less than 0.001 and r = -0.84, p = 0.002, respectively), but not in response to isoproterenol. Although isoproterenol produced a marked increase in cardiac output and LV dP/dt max (not explained by heart rate changes alone) in all patients, amrinone produced an increase in cardiac output only in those with markedly elevated LV filling pressures (who had a reduction in TSVR), and an increase in LV dP/dt in a minority.

Effect of increasing heart rate in patients with aortic regurgitation: Effect of incremental atrial pacing on scintigraphic, hemodynamic and thermodilution measurements☆

This study was performed to assess the effect of pacing-induced tachycardia in patients with aortic regurgitation. In 12 patients (5 men and 7 women with a mean age of 53 years) with aortic regurgitation, left ventricular end-diastolic and end-systolic volume indexes were measured with multigated equilibrium blood pool imaging, and forward cardiac index was determined with thermodilution, both at rest (mean heart rate +/- standard deviation 72 +/- 8 beats/min) and during atrial pacing at 100 and 120 beats/min. Pacing caused a decremental reduction in left ventricular end-diastolic and end-systolic volume indexes and radionuclide-determined stroke volume index but no change in radionuclide-determined cardiac index or left ventricular ejection fraction. Forward cardiac index increased incrementally from the baseline value at rest to that at 120 beats/min despite a decremental reduction in stroke volume index. There was a stepwise decrease in regurgitant volume/stroke (46 +/- 20 ml/m2 at baseline, 27 +/- 15 at 120 beats/min; p less than 0.05) but no change in regurgitant volume/min (3.38 +/- 1.80 liters/min per m2 at baseline, 3.22 +/- 1.78 at 120 beats/min; difference not significant [NS]) or regurgitant fraction (0.54 +/- 0.13 at baseline, 0.49 +/- 0.13 at 120 beats/min; NS). Mean femoral arterial, pulmonary arterial and pulmonary capillary wedge pressures did not change with pacing.