Systolic and diastolic flow abnormalities in elderly patients with hypertensive hypertrophic cardiomyopathy.

Seventeen patients with clinical and echocardiographic features of hypertensive hypertrophic cardiomyopathy of the elderly were studied to more completely characterize left ventricular systolic and diastolic function in this group. Measurements of left ventricular structure and systolic and diastolic function were made in the study patients and compared with those of age-matched control subjects. The study group had significantly greater left ventricular mass, wall thickness, shortening fraction and relative wall thickness than did the control subjects. Left ventricular end-diastolic dimension was smaller and left atrial size was not different in study patients compared with control subjects. Left ventricular filling was characterized by an increased peak atrial velocity and reduced ratio of peak early to peak atrial velocity in the study group. Left ventricular outflow velocities were elevated in 14 of the 17 study patients with peak velocities ranging from 1.2 to 5.0 m/s corresponding to a peak intraventricular gradient of 16 to 100 mm Hg. The velocity waveforms in these patients were late-peaking, similar to those described in hypertrophic obstructive cardiomyopathy. The elevated velocities were localized to the left ventricular outflow tract. These findings imply a pathophysiologic state in these elderly patients with long-standing hypertension, very similar to that in hypertrophic obstructive cardiomyopathy, and provide further support for the use of pharmacologic agents with negative inotropic properties or positive lusitropic properties in this group.

Effects of pharmacologic coronary hyperemia on echocardiographic left ventricular function in patients with single vessel coronary artery disease.

To assess whether pharmacologic coronary vasodilation could provoke new left ventricular wall motion abnormalities in patients with single vessel coronary artery disease, systemic hemodynamics, coronary blood flow velocity and left ventricular wall motion were measured by two-dimensional echocardiography during administration of 10 mg of intracoronary papaverine in 14 patients before and again immediately after left coronary angioplasty (group 1). As a comparison with an intravenous method, left ventricular wall motion was analyzed after 0.56 mg/kg body weight of intravenous dipyridamole in a separate group of 13 patients with single vessel coronary disease (group 2). Heart rate-blood pressure product increased 3% to 6% in papaverine-treated patients and 14 +/- 11% (p = NS) in dipyridamole-treated patients. No angiographic collateral vessels were present in either group. Although intracoronary mean flow velocity measured in the 14 group 1 patients and in 5 normal control subjects during papaverine treatment increased from 125% to 400% of basal flow velocity, papaverine induced new left ventricular wall motion abnormalities in only 5 of the 14 patients before coronary angioplasty. In three of five patients, left ventricular wall motion abnormalities persisted after successful coronary angioplasty. Four of the 14 patients demonstrated augmentation of left ventricular wall motion with papaverine. After intravenous dipyridamole, only 3 of the 13 group 2 patients developed new left ventricular regional asynergy. These data suggest that selective (papaverine) and, most likely, global (dipyridamole) augmentation of coronary flow alone does not reliably identify potential ischemic left ventricular regions affected by critical single vessel coronary artery disease.

Echocardiographic evaluation of cardiac structure and function in elderly subjects with isolated systolic hypertension.

One hundred four participants in the Systolic Hypertension in the Elderly Program (SHEP) trial (mean age 71 +/- 6 years) were examined by Doppler echocardiography to gain information on the cardiac structural and functional alterations in isolated systolic hypertension. Participants had a systolic blood pressure greater than 160 mm Hg with diastolic blood pressure less than 90 mm Hg and were compared with 55 age-matched normotensive control subjects. Left ventricular mass index was significantly higher in the participants than in the normotensive subjects (103 +/- 28 versus 87 +/- 23 g/m2, p = 0.0014) and 26% of the participants met echocardiographic criteria for left ventricular hypertrophy compared with 10% of normotensive subjects. Left atrial index was also greater in participants than in normotensive subjects (2.26 +/- 0.32 versus 2.11 +/- 0.24 cm/m2, p = 0.005) and 51% of participants had left atrial enlargement. Doppler measures of diastolic filling were significantly different between the two groups, with peak atrial velocity higher (76 +/- 17 versus 69 +/- 17 cm/s, p = 0.02) and ratio of peak early to atrial velocity lower (0.76 +/- 0.23 versus 0.86 +/- 0.22, p = 0.0124) in participants. There was no correlation between left ventricular mass index and Doppler measures of diastolic function, but relative wall thickness correlated significantly with peak atrial velocity (r = 0.22, p = 0.016) and peak early to peak atrial velocity ratio (r = 0.24, p = 0.007). There was no difference in M-mode ejection phase indexes of systolic performance (shortening fraction and peak velocity of circumferential fiber shortening) between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Impaired coronary vasodilator reserve in the immediate postcoronary angioplasty period: analysis of coronary artery flow velocity indexes and regional cardiac venous efflux.

The ratio of peak hyperemic/basal mean coronary flow velocity, an index of coronary vasodilator reserve, immediately after coronary angioplasty normalizes in less than 50% of patients. To evaluate other indexes of coronary vasodilator capacity, both intracoronary arterial velocity and cardiac venous efflux were measured at rest and during vasodilator-induced coronary hyperemia (intracoronary nitroglycerin and papaverine) before and after angioplasty in 27 patients; 17 patients had measurements of intracoronary velocity alone and 10 had thermodilution measurements of great cardiac vein flow. Coronary flow velocity responses were also measured in 6 angiographically normal segments in patients undergoing angioplasty and in 10 normal left coronary artery segments in patients with normal coronary arteries or isolated right coronary artery disease. Despite significant angiographic (72 +/- 12 to 23 +/- 11% diameter narrowing) and hemodynamic (49 +/- 12 to 19 +/- 12 mm Hg aortocoronary gradient) improvement, coronary vasodilator reserve ratios for both arterial velocity and venous flow after angioplasty were only minimally affected. Angioplasty did not significantly increase rest coronary vein flow or artery flow velocities, but did result in significantly higher papaverine responses after angioplasty. Mean and phasic coronary velocity, diastolic coronary flow velocity integral and measured great cardiac vein flow ratios were significantly lower when compared with those in 16 angiographically normal coronary artery segments. These data indicate that maximal hyperemic coronary flow velocity is increased after angioplasty, but the reserve ratios, calculated by any of several flow velocity indexes, remain minimally improved. Angiographic correlations (percent coronary diameter, absolute diameter or cross-sectional area) with variables of coronary blood flow or velocity suggest that no single variable is useful in assessing angioplasty results. However, postangioplasty arterial mean velocity and diastolic flow velocity integral are nearly normalized in most patients, whereas relative changes remain attenuated. These findings are important in studies assessing coronary vasomotor responses in patients with atherosclerotic coronary disease, especially after angioplasty.

Immediate and short-term effects of aortic balloon valvuloplasty on left ventricular diastolic function and filling in humans.

The effect of aortic balloon valvuloplasty on left ventricular diastolic function and filling was investigated in 44 adult patients with severe aortic stenosis. Two-dimensional and Doppler echocardiography was performed in all patients before and 24 h after valvuloplasty. In 19 patients (short-term group) repeat studies were performed at 3 (n = 2) and 6 (n = 17) months. Left ventricular relaxation, chamber stiffness and filling were assessed in 16 patients (immediate post-valvuloplasty group) before and immediately after valvuloplasty by simultaneous micromanometer left ventricular pressure tracings and echocardiograms. Immediately after valvuloplasty, relaxation was slightly impaired in the immediate post-valvuloplasty group, as reflected by the isovolumic relaxation time constant (56 +/- 26 to 68 +/- 39 ms; p less than 0.01) and maximal negative dP/dt (2,063 +/- 640 to 1,767 +/- 495 mm Hg/s; p less than 0.001). The chamber stiffness constants and diastolic filling dynamics were unchanged immediately after valvuloplasty. Twenty-four hours after valvuloplasty, patients without mitral regurgitation (n = 24) showed increases in the peak early filling velocity (72 +/- 31 to 83 +/- 28 cm/s; p less than 0.05) and peak early to atrial filling velocity ratio (0.8 +/- 0.6 to 1.0 +/- 0.7; p less than 0.05). However, in patients with mitral regurgitation (n = 20), the diastolic filling dynamics were not significantly changed. In the short-term group at the 3 to 6 month follow-up period, patients without mitral regurgitation (n = 12) showed striking increases compared with pre-valvuloplasty values in the peak early filling velocity (66 +/- 21 to 93 +/- 31 cm/s; p less than 0.02), peak early to atrial filling velocity ratio (0.6 +/- 0.2 to 0.9 +/- 0.4; p less than 0.02) and early time-velocity integral (9 +/- 4 to 16 +/- 6 cm; p less than 0.002). In patients with mitral regurgitation (n = 7) decreases occurred in the peak early filling velocity (123 +/- 32 to 106 +/- 28 cm/s; p less than 0.05) and peak early to atrial filling velocity ratio (1.5 +/- 0.7 to 1.1 +/- 0.6; p less than 0.05). Functional class in hospital improved after valvuloplasty (3.1 +/- 1.0 to 2.6 +/- 0.9; p less than 0.001) and correlated modestly with the percent decrease in Doppler-derived peak gradient (rs = 0.41, p less than 0.02) and mean gradient (rs = 0.36, p less than 0.05), but did not correlate with changes in aortic valve area, left ventricular ejection fraction or diastolic filling variables.(ABSTRACT TRUNCATED AT 400 WORDS)

Mechanism of blood flow generated by precordial compression during CPR. I. Studies on closed chest precordial compression.

The mechanism of forward flow produced by precordial compression during CPR was investigated with the aid of echocardiographic and hemodynamic measurements in anesthetized, mechanically ventilated domestic pigs. Both mitral and tricuspid valves opened during compression diastole and closed during compression systole. Valve motion persisted throughout resuscitation in 17 of 22 animals which were hemodynamically resuscitated. There was a 25 percent reduction in left ventricular area during compression systole. Maximum pressure generated during compression systole in the aorta exceeded that of the right atrium throughout the 12-min interval of precordial compression in successfully resuscitated animals. These observations provide evidence of direct cardiac compression as the mechanism accounting for effective forward blood flow during CPR. The persistence of valve function, chamber compression, and pressure gradients during precordial compression was predictive of successful resuscitation. The absence of these factors prognosticates failure of resuscitation and explains, in part, the inconsistency of prior reports.

Increases in coronary vein CO2 during cardiac resuscitation.

We investigated the aortic, mixed venous, and great cardiac vein acid-base changes in eight domestic pigs during cardiac arrest produced by ventricular fibrillation and during cardiopulmonary resuscitation (CPR). The great cardiac vein PCO2 increased from a control value of 52 +/- 2 to 132 +/- 28 (SD) Torr during CPR, whereas the arterial PCO2 was unchanged (39 +/- 4 vs. 38 +/- 4). The coronary venoarterial PCO2 gradient, therefore, increased remarkably from 13 +/- 2 to 94 +/- 29 Torr. The simultaneously measured great cardiac vein lactate concentrations increased from 0.24 +/- 0.06 to 7.3 +/- 2.34 mmol/l. Much more moderate increases in the lactate content of aortic blood from 0.64 +/- 0.25 to 2.56 +/- 0.27 mmol/l were observed. Increases in great cardiac vein PCO2 and lactate were highly correlated during CPR (r = 0.91). After successful CPR, the coronary venoarterial PCO2 gradient returned to normal levels within 2 min after restoration of spontaneous circulation. Lactate content was rapidly reduced and lactate extraction was reestablished within 30 min after CPR. These studies demonstrate marked but reversible acidosis predominantly as the result of myocardial CO2 production during CPR.

Effects of tromethamine and sodium bicarbonate buffers during cardiac resuscitation.

The effects on cardiac resuscitability of iso-osmolal solutions of tris-hydroxymethyl-aminomethane (tromethamine), sodium bicarbonate (NaHCO3) and sodium chloride placebo were compared in 30 domestic pigs using a well-established model of electrically induced cardiac arrest and resuscitation. We hypothesized that a carbon dioxide (CO2) consuming buffer like tromethamine would reduce and sodium bicarbonate would increase the respiratory acidosis of mixed venous blood, which had recently been demonstrated in our laboratory, Tromethamine did decrease and sodium bicarbonate did increase both arterial and mixed venous CO2 during cardiopulmonary resuscitation (CPR). Both concentrations of end-tidal CO2 and coronary venous PCO2 were significantly lower after tromethamine than after bicarbonate. However, tromethamine produced an unexpected vasodilator effect with reduction of mean aortic and coronary perfusion pressures to levels that are known to reduce resuscitability and survival independently of its buffer action. Neither resuscitability nor survival was altered by bicarbonate therapy in comparison with sodium chloride placebo.

Micelle formation of amphiphilic polystyrene-b-poly(N-vinylpyrrolidone) diblock copolymer in methanol and water-methanol binary mixtures.

The micelle formation by the amphiphilic polystyrene-block-poly(N-vinylpyrrolidone) (PS48-b-PNVP99) copolymer is investigated in methanol and water-methanol binary mixtures of various compositions using 1H NMR, fluorescence spectroscopy, static/dynamic light scattering (SLS/DLS), and transmission electron microscopy (TEM). Critical micelle concentrations (cmc) are determined by employing fluorescence spectroscopy and DLS measurements. The cmc of the PS48-b-PNVP99 block copolymer increases with increasing methanol content in the water-methanol binary mixtures, suggesting that methanol is a better solvent for the PS48-b-PNVP99 block copolymer than water-methanol mixtures or pure water. The amphiphilic PS48-b-PNVP99 diblock copolymer forms spherical micelles of Rh approximately 16 nm in pure methanol solution as revealed by DLS measurements. In contrast, significantly larger micelles having higher aggregation numbers are formed in water-methanol binary mixtures. Temperature dependent data reveal an increase in aggregation number and radius of gyration (Rg) concomitantly with temperature (10-40 degrees C). In contrast, the overall size (Rh) of the micelles remains almost constant over the same temperature range. An explanation is tendered that PNVP coronas dehydrate/desolvate at higher temperatures counteracting the increase in micelle size (Rh) caused by increased aggregation numbers (Nagg).

Effects of aging on left ventricular structure and function.

To better characterize the cardiac structural and functional changes that are associated with aging, Doppler-echocardiography was performed on 23 young (mean age, 25 years) and 30 old (mean age, 70 years) healthy normotensive subjects. Left ventricular cavity dimensions and wall thickness were determined and left ventricular mass index was calculated from M-mode echocardiograms. Stroke volume was calculated from Doppler-measured aortic flow. Diastolic filling was evaluated by pulsed Doppler echocardiography of mitral inflow. Posterior wall thickness (1.0 vs 0.8 cm, p less than 0.05) and relative wall thickness (0.42 vs 0.35, p less than .05) were significantly greater in the elderly subjects compared with the younger subjects. Left ventricular mass index increased on average 0.25 gm/m2/yr but was not significantly increased in the elderly compared with the younger subjects (89 vs 77 gm/m2). Shortening fraction and stroke volume did not differ between the two groups. Diastolic filling was dramatically altered with aging, and the elderly subjects demonstrated a doubling of percent atrial contribution (37% vs 19%, p less than 0.0001) and halving of peak early-to-peak atrial velocity ratio (0.85 vs 1.77, p less than .01).

Expired carbon dioxide: a noninvasive monitor of cardiopulmonary resuscitation.

End-tidal CO2 concentration (ETCO2) may serve as a simple noninvasive measurement of the blood flow generated by precordial compression during cardiopulmonary resuscitation (CPR). In a mechanically ventilated porcine preparation of ventricular fibrillation, onset of fibrillation was associated with a rapid decrease in ETCO2 from 4.0 +/- 0.2% to less than 0.7 +/- 0.2%. With precordial compression, it increased to 1.9 +/- 0.3%. Animals that were successfully defibrillated after 12 min of CPR demonstrated an immediate increase in ETCO2. The ETCO2 increased from 1.9 +/- 0.3% to 4.9 +/- 0.3% over an interval of between 30 and 60 sec. These changes in ETCO2 were closely related to proportionally similar decreases and increases in cardiac output (CO), and a close correlation between ETCO2 and CO was demonstrated (r = .92). A similar highly significant correlation between ETCO2 and CO was also demonstrated during open-chest cardiac massage (r = .95). ETCO2 therefore serves as a noninvasive measure of pulmonary blood flow and therefore CO. In 17 successfully resuscitated animals. ETCO2 during precordial compression averaged 1.7 +/- 0.2%, whereas it was only 0.5 +/- 0.1% in five animals in whom resuscitation procedures were unsuccessful (p less than .001). Accordingly, ETCO2 prognosticates outcome during CPR and immediately identifies restoration of spontaneous circulation.

Effect of abruptly increased intrathoracic pressure on coronary blood flow velocity in patients.

To assess the effects of abruptly increased intrathoracic pressure on coronary blood flow, arterial pressure, heart rate, and intracoronary Doppler blood flow velocity were measured continuously during cough(s) and again during the four phases of the Valsalva maneuver in 14 patients. Coughing significantly increased the systolic pressure (137 +/- 25 to 176 +/- 30 mm Hg), diastolic pressure (72 +/- 10 to 84 +/- 18 mm Hg), and arterial pulse pressure (65 +/- 27 to 92 +/- 35 mm Hg), with no change in heart rate. The mean coronary flow velocity decreased (17 +/- 10 to 14 +/- 12 cm/sec, p less than 0.03). During the Valsalva maneuver, despite marked reduction in the mean arterial pressure during phase III (96 +/- 12 to 68 +/- 14 mm Hg, p less than 0.05), the reduction of coronary blood flow velocity did not achieve statistical significance. These data demonstrate that neither type of abrupt physiologic increase in intrathoracic pressure enhances coronary blood flow. Coughing does not improve coronary perfusion pressures or flow velocity, despite marked increases in arterial diastolic pressure. The Valsalva maneuver, for the most part, does not significantly alter coronary blood flow velocity.

Ventricular arrhythmia due to intracoronary papaverine: analysis of QT intervals and coronary vasodilatory reserve.

Intracoronary papaverine commonly produces striking QT interval prolongation with rare but serious ventricular dysrhythmias reported. Because of 3 cases of severe papaverine-induced dysrhythmia in our laboratory, QT intervals and hemodynamic and intracoronary velocity data collected during intracoronary papaverine administration were retrospectively reviewed in 34 patients; 20 patients with angiographically normal coronary arteries (group 1) and 14 patients (group 2) before and (group 2) after single-vessel left coronary angioplasty. QT intervals increased from 394 +/- 44 to 464 +/- 73 msec, 414 +/- 47 to 504 +/- 95 msec, and 410 +/- 41 to 486 +/- 75 msec for groups 1 and 2 before and after angioplasty, respectively (all P less than 0.01). There was no correlation with hemodynamic, electrocardiographic, or coronary vasodilatory reserve responses and change in QTc interval. In the 3 index patients having significant papaverine-related arrhythmias, a baseline QT interval was prolonged (after prior papaverine exposure) in only 1 in association with torsade de pointes. These data indicate that QT interval prolongation after papaverine is a common occurrence, but that the production of ventricular dysrhythmia is probably idiosynchratic in origin. In view of these findings, we recommend that appropriate antiarrhythmic preparations be in place for patients receiving intracoronary papaverine.

Preliminary experience with 5 and 6 French diagnostic catheters as guiding catheters for coronary angioplasty.

With the reduction in profile of balloon dilation catheters, until recently, it has been the internal dimensions and performance of the guiding catheter that has mandated the use of 7, 8 or 9 French (F) systems for the performance of percutaneous transluminal coronary angioplasty (PTCA). A new 5F catheter design (Sherwood Medical Co., St. Louis, MO) provided a large inner lumen (0.4") permitting use of 0.20-0.22" fixed-wire PTCA balloon catheters with good coronary visualization. Potential advantages include reduced coronary artery ostial trauma and catheter induced damping and enhanced patient comfort. We report our initial experience in 14 patients undergoing PTCA with a 5 and 6F guide/fixed-wire system. Mean age was 63 +/- 10 (43-78 years). PTCA indications: Cardiogenic shock (1), post-myocardial infarction angina pectoris (2), grade III angina (5) and unstable angina pectoris (6). Vessel attempted: Left anterior descending (3), circumflex (4), obtuse marginal (2), diagonal (1), right coronary artery (3), and internal thoracic artery (1). Twelve patients had femoral approach; two brachial approach. The USCI Probe (USCI Division, Billerica, MA) was used in 8 lesions and SCIMED ACE (SCIMED Life Systems, Maplegrove, MN) catheter in 7 lesions. Successful 5 or 6F guide/fixed-wire dilations reduced the stenosis (77 +/- 14 to 37 +/- 30%) and were successfully performed in 79% (11/14). One 5F patient required 8F guiding catheter and was dilated with 2.0 fixed-wire balloon. A second failed 5F PTCA could not be dilated with any larger conventional system. A third total occlusion could not be crossed with a guidewire or fixed wire balloon. No patient had a complication.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of high (sodium meglumine diatrizoate, Renografin-76) and low osmolar (sodium meglumine ioxaglate, Hexabrix) radiographic contrast media on diastolic function during left ventriculography in patients.

Although a majority of studies indicate superior hemodynamic and clinical profiles of low osmolar compared with high osmolar contrast media, the effect of these agents on diastolic left ventricular function has not been examined. We prospectively examined hemodynamic, electrocardiographic, and echocardiographic indices of left ventricular function in patients undergoing contrast ventriculography with a high osmolar, ionic, monomeric contrast, diatrizoate (Renografin-76) compared with a low osmolar, ionic, dimeric contrast, ioxaglate (Hexabrix). Thirty patients were randomized to each group. There were no clinical differences between the two groups. The decrease in systemic pressures was significantly greater with diatrizoate after left ventriculography (-38.5 +/- 3.5 versus -18.2 +/- 2.3, p less than 0.001) and selective left coronary angiography (-29.5 +/- 2.4 versus -17.4 +/- 2.6, p less than 0.001). In addition, left ventricular end-diastolic pressure increased significantly more with diatrizoate (7.3 +/- 0.9 versus 2.7 +/- 0.8 mm Hg for ioxaglate, p less than 0.001). QT interval prolongation occurred in both patient groups. Diatrizoate decreased systemic vascular resistance, and increased cardiac output and left ventricular ejection fraction more than ioxaglate, while simultaneously increasing left ventricular end-diastolic volume and altering the peak atrial filling velocity. Negative dp/dt (p less than 0.05), but not Tau, computed by the logarithmic or derivative methods, was reduced by diatrizoate. These data indicate that significant alteration of diastolic filling patterns occurs with high osmolar compared with low osmolar contrast agents. Although the clinical significance of this observation is currently unknown, these data further support the reported hemodynamic superiority of the low osmolar, dimeric contrast agent ioxaglate during contrast angiography.