Joseph P. Murgo

Effects of age on ventricular-vascular coupling

The effects of age on the interrelation between the physical properties of the arterial tree (aortic input impedance) and left ventricular performance (cardiac output) were studied in 45 subjects, aged 19 to 62 years, without apparent cardiovascular disease. Ascending aortic pulsatile pressure and blood flow velocity were measured with a multisensor catheter and cardiac output by green dye or the Fick method. Heart rate and end-diastolic aortic pressure remained unchanged with age, whereas aortic systolic, mean and pulse pressures and aortic radius increased. In subjects younger than 30 years, early systolic pressure usually exceeded late systolic pressure (type C beat); in subjects older than 50 years, late systolic pressure usually exceeded early systolic pressure (type A beat). In 55% of subjects aged 30 to 50 years, early and late systolic pressures were essentially equal (type B beat). The impedance spectra from all subjects showed fluctuations about the characteristic impedance (index of elastance) that were greater in the older subjects. Peripheral resistance increased 37% (r = 0.47, p less than 0.001) over the age range of 20 to 60 years, whereas characteristic impedance increased 137% (r = 0.66, p less than 0.001). The fundamental impedance modulus increased, and the impedance modulus minimum shifted to a higher frequency. These changes in the impedance spectral pattern indicate that the ascending aorta becomes stiffer and the cross section of the peripheral vascular bed decreases with age, causing increased pulse wave velocity and wave reflection.(ABSTRACT TRUNCATED AT 250 WORDS)

Percutaneous angioscopy during coronary angioplasty using a steerable microangioscope

The feasibility of using a flexible, steerable angioscope to perform coronary angioscopy before and after percutaneous coronary angioplasty was tested. The microangioscope fits through an 8F coronary angioplasty guiding catheter and contains a multifiber viewing bundle incorporated into the body of a 4.3F balloon catheter with a central lumen for distal flushing and guide-wire passage. Angioscopy was performed without complications 45 times in 24 patients, including 6 patients with stable and 18 with unstable angina. Circumferential visualization of the target lesion was successful in 20 (83%) of the 24 patients and improved with operator experience. Excellent visualization of the target lesion was achieved in 16 (94%) of the last 17 patients. Plaque, thrombus and dissection were among the abnormal findings in the 20 patients (4 with stable, 16 with unstable angina) in whom circumferential viewing of the target lesion was achieved. In four patients with restenosis after angioplasty, the lesion morphology was distinctly different from that of lesions in arteries without prior angioplasty. In patients with stable angina, no thrombus or dissection was seen by angiography or angioscopy before angioplasty. In patients with unstable angina, thrombus was detected more frequently by angioscopy than by angiography before angioplasty (8 versus 2 of 16) and after (15 versus 2 of 16) angioplasty. Intimal dissection was also seen much more frequently by angioscopy than by angiography before angioplasty (7 versus 0 of 16) and after angioplasty (16 versus 7 of 16). It is concluded that high resolution percutaneous coronary angioscopy can be performed safely in conjunction with balloon angioplasty. Further investigation is needed before this diagnostic tool can be applied clinically.

Manipulation of ascending aortic pressure and flow wave reflections with the Valsalva maneuver: relationship to input impedance.

SUMMARY Dramatic changes in the shape of pulsatile ascending aortic pressure and flow wave forms occur during the Valsalva maneuver in man. To study these changes, aortic pressure and flow signals were recorded in eight patients using a multisensor catheter. Aortic input impedance was derived during the control, strain and postrelease phases of the Valsalva maneuver. During control, well-defined minima and maxima occurred in the spectral plots of impedance moduli. This pattern was accentuated during the postrelease phase. In contrast, input impedance during strain was almost equal to the characteristic impedance for all harmonics. These results imply that during the control and postrelease phases, strong reflections return to the ascending aorta, but during the strain phase, reflections are minimal, absent or more diffuse. From wave transmission theory, it also follows that pulsatile pressure and flow wave forms should be similar in shape in the absence of reflections and dissimilar in the presence of reflections. This was observed in all eight patients. By provoking changes in the arterial tree during the Valsalva maneuver, the magnitude and timing of wave reflections were significantly altered, resulting in marked changes in the shape of pulsatile aortic pressure and flow wave forms. This study demonstrates the importance of reflections in determining the shape of the arterial pulse.

Effects of exercise on aortic input impedance and pressure wave forms in normal humans.

The effects of supine bicycle exercise on the input impedance of the ascending aorta were studied in thirteen male subjects undergoing cardiac catheterization, but in whom no cardiovascular disease was found. Ascending aortic flow velocity and pressure were recorded simultaneously from a multisensor catheter with an electromagnetic flow velocity probe and a pressure sensor mounted at the same location. A second pressure sensor at the catheter tip provided left ventricular pressure. Fick cardiac outputs were used to scale the velocity signal to instantaneous volumetric flow. Input imped- ance was calculated from 10 harmonics of aortic pressure and flow. For each subject, impedance moduli and phases from a minimum of 15 beats during rest and exercise were averaged. Peripheral resistance decreased from a resting value of 1142 ± 51 (± SE) dynes sec/cm6 to 712 ± 39 dynes sec/cm6 during exercise. Characteristic impedance remained unchanged with a resting value of 47 ± 4 dynes sec/cm5and an exercise value of 45 ± 4 dynes sec/cm5. These results were associated with an increase in aortic pressure (96 ± 2 to 111 ± 2 mm Hg) and pulse wave velocity implying a decrease in aortic compliance. An increase in aortic cross-sectional area apparently offsets the effects of these changes in compliance and pulse wave velocity to result in an unchanged characteristic impedance. The increase in pulse wave velocity caused wave reflections to occur earlier during exercise, but the general characteristics of the pressure wave shapes remained unchanged. Circ Res 48: 334-343, 1981

Location of a Reflection Site Is Elusive: Consequences for the Calculation of Aortic Pulse Wave Velocity

Aortic pulse wave velocity (PWV), a measure of aortic stiffness, is an important indicator of cardiovascular risk. Derivation of PWV from uncalibrated proximal aortic or carotid pressure alone has practical advantages. However, when the time of return of the reflected wave, &Dgr;t, is used to calculate PWV, inaccurate data are obtained. With aging PWV increases but &Dgr;t hardly decreases, suggesting that the reflection site moves toward the periphery. We hypothesized that the forward and reflected waves in the distal aorta are not in phase, leading to an undefined reflection site. We derived forward and backward waves, at the entrance and distal end of a uniform tube, with length “L.” With the tube closed at the end, forward and reflected waves are there in phase, and PWV=2L/&Dgr;t. When the tube is ended with the input impedance of the lower body, forward and backward waves at its end are not in phase, and &Dgr;t is increased, suggesting that the reflection site is further away (tube seems longer), and PWV calculated from 2L/&Dgr;t is underestimated. Using an anatomically accurate model of the human arterial system, we show that the forward and backward waves in the distal aorta are not in phase. When aortic PWV increases, &Dgr;t changes only little, and the reflection site appears to move to the periphery, similar to what is observed in humans. We conclude that to define the location of a reflection site is elusive and that PWV cannot be calculated from time of return of the reflected wave.

Clinical variables affecting recovery of left atrial mechanical function after cardioversion from atrial fibrillation

OBJECTIVES We sought to evaluate the effect of clinical factors on recovery of atrial function after cardioversion for atrial fibrillation. BACKGROUND Lack of effective mechanical atrial function (EMAF) after cardioversion of atrial fibrillation predisposes to thromboembolic complications and delays improvement in functional capacity. METHODS Fifty-two patients underwent cardioversion (group I, electrical cardioversion, n = 40; group II, pharmacologic or spontaneous cardioversion, n = 12) for atrial fibrillation. Serial transmitral inflow Doppler variables were recorded after cardioversion until EMAF (atrial filling velocity > 0.50 m/s) was seen. Clinical variables (age, duration of atrial fibrillation, left ventricular ejection fraction, left atrial diameter, underlying cardiovascular disease, antiarrhythmic drug therapy and mode of cardioversion) were tested for an association with the outcomes of recovery of atrial function by day 3 and day 7. RESULTS Effective mechanical atrial function recovered in 68% of patients by day 3 and in 76% by day 7 after cardioversion. The mode of cardioversion was significantly associated with recovery of atrial function by day 3 in bivariate and multivariate analyses (odds ratio 0.12, 95% confidence interval 0.01 to 1.0, for electrical cardioversion). None of the variables had an association with recovery of atrial function by day 7. Group I patients took a longer time to recover atrial function than group II patients (p = 0.012). In addition, group I patients had a significantly lower peak atrial filling velocity (mean [+/-SD] 0.39 +/- 0.19 m/s vs. 0.56 +/- 0.16 m/s) and a higher early filling to atrial filling velocity ratio (2.5 +/- 1.2 vs. 1.5 +/- 0.5) after cardioversion. CONCLUSIONS A high proportion of patients recover EMAF within 1 week after cardioversion. Patients who undergo electrical cardioversion display a greater degree and a longer duration of mechanical atrial dysfunction than those who convert pharmacologically or spontaneously.

Hemodynamics in transgenic mice with overexpression of atrial natriuretic factor.

The circulatory effects associated with lifelong plasma atrial natriuretic factor (ANF) elevation were examined by generating transgenic mice, which constitutively express a fusion gene consisting of the transthyretin promoter and the ANF structural gene. These mice have chronically elevated ANF levels as compared with their nontransgenic siblings. Transgenic animals exhibited immunoreactive ANF levels that were nearly fivefold higher than those measured in nontransgenic littermates. Systemic and regional hemodynamics and blood volumes were explored by using modifications of the reference microsphere and dilution techniques. Mean arterial pressure was reduced by 24 mm Hg, associated with a 27% reduction in total heart weight. This chronic reduction in blood pressure was due to a 21% reduction in total peripheral resistance, whereas cardiac output, stroke volume, and heart rate were not significantly altered, despite a 15% elevation in plasma volume. Transgenic mice displayed reductions of 35%, 33%, 32%, and 19% in muscle, skin, brain, and renal vascular resistance, respectively, whereas coronary and splanchnic resistances were not significantly altered. The findings complement earlier data from chronically infused normotensive mammals and suggest that these mice are an excellent model for investigating the effects of lifelong ANF elevation.

Myocardial contrast echocardiography: reliable, safe, and efficacious myocardial perfusion assessment after intravenous injections of a new echocardiographic contrast agent.

Reliable and reproducible myocardial opacification after intravenous administration of echocardiographic contrast agents has remained elusive. This study was performed to determine whether a new agent, FS069, a suspension of perfluoropropane-filled albumin microspheres (3.6 microns average microbubble size, concentration 8 x 8(8)/ml), could achieve safe and successful myocardial opacification in open-chest dogs. Seventeen dogs (group 1, n = 7, group 2, n = 10) underwent two-dimensional echocardiography before, during, and after the administration of intravenous FS069. Safety was evaluated by measuring arterial and pulmonary artery pressures, heart rate, blood gases, systolic function, myocardial blood flow, and postmortem analysis of myocardial viability by triphenyl-tetrazolium chloride staining. Efficacy to detect changes in regional myocardial perfusion was assessed by injecting FS069 at baseline, after sequential coronary occlusions and reperfusion, and during intravenous vasodilators with and without coronary occlusions. Results were compared with radiolabeled microspheres. FS069 was found to be safe and effective. In the absence of coronary occlusions, uniform myocardial opacification was observed in all dogs. A perfusion defect was observed in all dogs during coronary occlusions. Background-subtracted peak contrast intensity in the myocardium correctly identified regional myocardial blood flow changes and showed a significant correlation with radiolabeled microspheres (r = 0.65, p = 0.0001).

Prognostic Value of Stress Echocardiography in the Evaluation of Atypical Chest Pain Patients Without Known Coronary Artery Disease

Patients with atypical chest pain frequently lack significant coronary artery disease (CAD) and are, therefore, at low risk for future adverse cardiovascular events. We hypothesized that in this group of patients, stress echocardiography could identify those at risk for cardiac events. We retrospectively reviewed (mean follow-up 23.0 +/- 7.2 months) the prognostic value of stress echocardiography for major (cardiac death, myocardial infarction, congestive heart failure, and unstable angina) and total (major events plus coronary revascularization) cardiac events in 661 patients with atypical chest pain, normal global left ventricular (LV) systolic function, and no history of CAD. A positive stress echocardiogram was defined as the development of new or worsening wall motion abnormalities with exercise stress (80%) or dobutamine (20%). A total of 41 cardiac and 16 major events were noted. The event-free survival for total cardiac events was 97% for a normal stress echocardiogram and 93% for a normal stress electrocardiogram (ECG) at 30 months. A positive stress ECG predicted an event-free rate of 86% compared with 74% for stress-induced wall motion abnormalities and 42% if stress-induced LV dysfunction accompanied the wall motion abnormalities. A strategy recommending invasive studies based on positive stress echocardiogram results increased the per-patient cost, but led to greater savings per cardiac event predicted and provided incremental prognostic value for future cardiac events beyond clinical and stress electrocardiographic data. Thus, stress echocardiography in low-risk patients for CAD appears to be more cost effective than a stress ECG.

Benefits of reducing the cardiac cycle–triggering frequency of ultrasound imaging to increase myocardial opacification with FSO69 during fundamental and second harmonic imaging☆☆☆★★★

BACKGROUND Recent work has shown significant enhancement in myocardial contrast intensity with brief ultrasound pulsing gated to a discrete portion of the cardiac cycle over conventional 30 Hz imaging. We hypothesized that limiting ultrasound imaging to less than every cardiac cycle would further intensity the myocardial echo-contrast effect. We therefore sought to determine the best pulsing frequency for ultrasound imaging to achieve optimal myocardial perfusion after the intravenous administration of FSO69 using fundamental and second harmonic imaging. METHODS AND RESULTS In 13 male mongrel dogs, myocardial contrast opacification was determined while varying the cardiac cycle-triggering frequency of ultrasound imaging after intravenous injections of FSO69. Resulting myocardial echo-contrast intensities with a cardiac cycle-triggering frequency of every beat during end-diastole were compared with those with a cardiac cycle-triggering frequency of every third and fifth beat. Myocardial opacification, measured by background-subtracted peak intensity and visual scoring, was significantly greater when ultrasound imaging was triggered to every third and fifth beats compared with every beat. These benefits were seen with imaging in both the fundamental and second harmonic modes. Optimal myocardial opacification with FSO69 was achieved with injections as low as 0.1 ml, a dose that produced significant acoustic shadowing in only 24% of the injections. The degree of myocardial opacification was not significantly affected when the images were acquired during end-systole or end-diastole. CONCLUSIONS Electrocardiogram-gated ultrasound imaging to every third or fifth cardiac cycle greatly improves myocardial opacification compared with imaging each cardiac cycle. This benefit was increased twofold to threefold with the use of second harmonic imaging as compared with fundamental imaging.