George T. Daughters

Effect of Intrathoracic Pressure on Left Ventricular Performance

Left ventricular dysfunction is common in respiratory-distress syndrome, asthma and obstructive lung disease. To understand the contribution of intrathoracic pressure to this problem, we studied the effects of Valsalva and Müller maneuvers on left ventricular function in eight patients. Implantation of intramyocardial markers permitted beat-by-beat measurement of the velocity of fiber shortening (VCF) and left ventricular volume. During the Müller maneuver, VCF and ejection fraction decreased despite an increase in left ventricular volume and a decline in arterial pressure. In addition, when arterial pressure was corrected for changes in intrapleural pressure during either maneuver it correlated better with left ventricular end-systolic volumes than did uncorrected arterial pressures. These findings suggest that negative intrathoracic pressure affects left ventricular function by increasing left ventricular transmural pressures and thus afterload. We conclude that large intrathoracic-pressure changes, such as those that occur in acute pulmonary disease, can influence cardiac performance.

Alterations in left ventricular twist mechanics with inotropic stimulation and volume loading in human subjects.

BACKGROUND Left ventricular (LV) twist, the longitudinal gradient of circumferential rotation about the LV long axis, may play an important role in the storage of potential energy at end systole and its subsequent release as elastic recoil during early diastole; however, the effects of load and inotropic state on LV systolic twist and diastolic untwist in human subjects have not previously been characterized. METHODS AND RESULTS Six cardiac transplant recipients with 12 implanted radiopaque midwall LV myocardial markers were studied 1 year after transplantation. Biplane cinefluoroscopic marker images and LV pressure were recorded during control conditions and after afterload augmentation (methoxamine, 5 to 10 micrograms.kg-1 x min-1), inotropic stimulation (dobutamine, 5 micrograms.kg-1 x min-1), and preload augmentation (volume loading with normal saline). Systolic twist dynamics were assessed by maximum twist (Tmax[rad/cm]), peak negative twist rate (-dT/dtmin[rad.cm-1 x s-1]), and the slope of the twist normalized-ejection fraction relation (T-nEFR, Msys[rad/cm]) during systole. Diastolic untwist was assessed by the peak positive untwist rate (+dT/dtmax [rad.cm-1 x s-1]) and the slopes (rad/cm) of the T-nEFR during early diastole (Mear-dia) and mid diastole (Mmid-dia). Compared with control values, LV pressure and volume loading had no significant effect on Tmax, -dT/dtmin, or Msys; however, inotropic stimulation significantly increased all parameters describing systolic twist (Tmax: -0.10 +/- 0.03 versus -0.06 +/- 0.02 rad/cm, P < .001; -dT/dtmin: -0.72 +/- 0.19 versus -0.44 +/- 0.22 rad.cm-1 x s-1, P < .001; Msys: -0.10 +/- 0.03 versus -0.06 +/- 0.01 rad/cm, P < .001). Pressure loading had no effect on early diastolic untwisting; however, dobutamine significantly increased M(ear)-dia (-0.24 +/- 0.06 versus -0.13 +/- 0.04 rad/cm, P < .0001) and +dT/dtmax (0.78 +/- 0.24 versus 0.45 +/- 0.16 rad.cm-1 x s-1, P < .001). Conversely, volume loading significantly decreased M(ear)-dia (-0.08 +/- 0.04 versus -0.13 +/- 0.04 rad/cm, P < .05). M(ear)-dia correlated directly with LV contractile state (as assessed as maximum dP/dt, r = .60, P < .0001) and inversely with end-systolic volume (r = -.87, P < .0001) but was unrelated to stroke volume (r = .08, P = .30) or LV afterload (estimated as effective arterial elastance, r = .08, P = .29). Mmid-dia did not change during any intervention. CONCLUSIONS In conscious human transplant patients, (1) pressure and volume loading do not affect systolic LV twist; (2) dobutamine augments systolic twist and early diastolic untwisting, suggesting more end-systolic potential energy storage and early diastolic elastic recoil with enhanced inotropic state; (3) volume loading decreases early diastolic untwisting, possibly reflecting diminished recoil forces after preload augmentation associated with larger end-systolic volumes (ESV); and (4) M(ear)-dia correlates strongly with ESV (in an inverse fashion), and less strongly, but directly, with LV dP/dtmax.

Exercise response of the denervated heart in long-term cardiac transplant recipients

Abstract The left ventricular response to volume loading and graded supine bicycle exercise (3 minutes at 15, 45 and 90 watts) was assessed in nine long-term (more than 1 year) cardiac transplant recipients. Computer-aided fluoroscopy of radiopaque myocardial markers implanted in the left ventricle at the time of surgery was used to measure left ventricular dynamics. Pulmonary arterial and left ventricular pressures were monitored. Plasma norepinephrine was measured by radio-enzymatic assay at each level of exercise. Early in exercise mean end-diastolic volume (six patients) increased from a resting value of 125 to 138 ml (p

Geometric Distortions of the Mitral Valvular-Ventricular Complex in Chronic Ischemic Mitral Regurgitation

Background—Better understanding of the precise 3-dimensional geometric changes of the mitral valvular-ventricular complex in chronic ischemic mitral regurgitation (CIMR) is needed in order to devise better surgical repair techniques. We hypothesized that changes after inferior myocardial infarction would be different in hearts that developed CIMR compared with those that did not. Methods and Results—Twenty-four sheep underwent coronary snare and marker placement (annulus, papillary muscles, and anterior and posterior leaflets). After 8 days, cinefluoroscopy provided 3-dimensional marker data, and snare occlusion of obtuse marginal branches created inferior myocardial infarction, including the posterior papillary muscle. After 7 weeks, the 16 surviving animals were studied again and grouped by mitral regurgitation grade (≥ 2+, n=10 versus ≤ 1+, n=6). End-systolic mitral annulus dimensions, components of papillary muscle and leaflet displacement, were calculated. After inferior myocardial infarction, total displacement of the posterior papillary muscle from the midseptal annulus (“saddle horn”) was greater in CIMR(+) animals: 6.5±3.2 versus 3.1±2.7 (P =0.02), with the posterior papillary muscle moving more laterally (6.8±3.4 versus 2.5±3.5 mm, P =0.01). Increase in mitral annular septal-lateral diameter was greater in animals with CIMR (4.9±2.7 versus 2.3±2.0, P =0.02), and apical displacement of the posterior leaflet (PL) margin was also greater in the CIMR(+) group (1.7±1.0 versus 0.3±0.5, P =0.01). Conclusions—The CIMR(+) group had greater septal-lateral annular dilatation, lateral posterior papillary muscle displacement, and apical PL restriction, indicating that these associated geometric alterations may be important in the pathogenesis of CIMR. Treatment of CIMR should address both annular septal-lateral dilatation and lateral displacement of the posterior papillary muscle.

Alterations in left ventricular diastolic twist mechanics during acute human cardiac allograft rejection.

BACKGROUND Contraction of obliquely oriented left ventricular (LV) fibers results in a twisting motion of the left ventricle. The purpose of this study was to assess the effects of acute human cardiac allograft rejection on LV twist pattern and the twist-volume relation. METHODS AND RESULTS Tantalum markers were implanted into the LV midwall in 15 transplant recipients to measure time-varying, three-dimensional chamber twist using computer-assisted analysis of biplane cinefluoroscopic images. Twist was defined as the mean longitudinal gradient of circumferential rotation about the LV long axis. When plotted against normalized percent ejection fraction (%EF), the resulting twist-normalized %EF relation could be divided into three phases. In systole, LV twist was linearly related to ejection of blood. In contrast, diastolic untwist was characterized by early rapid recoil with little change in LV volume, followed by more gradual untwisting when the bulk of diastolic filling occurred. During 10 acute rejection episodes in 10 patients, maximum twist, peak systolic twist rate, and the slope of the systolic twist-normalized %EF relation did not change. In contrast, the slope of the early (first 15% of filling) diastolic twist-normalized %EF relation (M(early-dia)) decreased significantly (-0.194 +/- 0.062 [prerejection] versus -0.103 +/- 0.054 rad/cm [rejection], p = 0.0003), resulting in a prolonged tau 1/2 (time required to untwist by 50% [20 +/- 5% versus 28 +/- 5% of diastole], p = 0.0003) and decrease in percent untwisting at 15% diastolic LV filling (62 +/- 11% versus 36 +/- 13%, p = 0.0003). Therefore, a greater proportion of LV untwisting occurred later in diastole during rejection, as reflected by an increase in the slope (M(mid-dia)) of the middle to late (from 15 to 90% filling) diastolic twist-normalized %EF relation (-0.018 +/- 0.009 versus -0.030 +/- 0.010 rad/cm, p = 0.0015). Peak rate of untwist was not affected. With resolution of rejection, M(early-dia) and percent untwist during early diastole returned to baseline levels (p = NS versus baseline). There was also a trend for M(mid-dia) to return toward prerejection values (p = NS versus baseline), but this change did not reach statistical significance compared with rejection values. CONCLUSION Acute cardiac allograft rejection is associated with altered diastolic twist mechanics in the absence of any demonstratable systolic abnormalities. During rejection, myocardial edema and other factors may result in intrinsic changes of the elastic properties of the myocardium, thereby leading to modification of recoil forces responsible for the early, rapid unwinding of the deformed ventricle.

Torsional deformation of the left ventricular midwall in human hearts with intramyocardial markers: regional heterogeneity and sensitivity to the inotropic effects of abrupt rate changes

The spiral orientation of left ventricular (LV) fibers suggests that twisting about the ventricular long axis of the apex with respect to the base, i.e., torsional deformation, may be characteristic of LV contraction. To demonstrate this twisting motion, 10 orthotopic human cardiac allograft recipients were studied with biplane cineradiography of tantalum helices implanted within the LV midwall at 12 specific sites. Counterclockwise twisting about the LV long axis (as reviewed from apex to base) accompanied ventricular ejection in all patients. Torsional deformation angles, measured relative to a reference minor axis at the base, were substantially smaller in the anteroapical wall, as compared with counterparts in the apical third of the inferior and lateral walls (anterior = 13.3 ±6.0±, inferior =18.7±6.3±, and lateral = 23.4±10.7±). Torsional angles at the midventricular level were roughly half as much and exhibited similar regional variabilities (anterior = 7.6 ±3.3±, inferior = 9.0±3.3±, lateral = 10.7 ±5.2±, and septal = 8.8±3.8±). Comparison of control beats and the initial beat after abrupt cessation of rapid atrial pacing (126 ± 10 beats/min) with return to the control heart rate (96 ±9 beats/min) permitted the mild positive inotropic effect of tachycardia to be assessed at similar levels of ventricular load. Torsional deformation of the anteroapical and inferoaplcal sites increased significantly (p < 0.05) over control values to 15.6 ±7.5± and 21.2 ±5.5±, respectively. In contrast, torsional deformation of the lateral wall was essentially unchanged. These data provide direct evidence for torsional deformation of the left ventricle in humans, demonstrate that torsion of the LV chamber is nonuniform, and suggest a dependence of LV torsion upon contractile strength that is attenuated in the lateral wall.

Restricted posterior leaflet motion after mitral ring annuloplasty

BACKGROUND The effects of ring annuloplasty on mitral leaflet motion are incompletely known. The three-dimensional dynamics of the mitral valve in vivo were examined to determine how two types of annuloplasty rings affect leaflet motion during valve closure. METHODS Miniature radiopaque markers on the mitral leaflets, annulus, and left ventricle were implanted in three groups of sheep. One group served as control (n = 7); other sheep were randomly assigned to receive either a flexible Duran (n = 6) or a semirigid Carpentier-Edwards Physio ring (n = 6). After recovery, three-dimensional marker coordinates were computed from simultaneous (60 Hz) biplane videofluoroscopic marker images. RESULTS Both types of rings immobilized the middle scallop of the posterior leaflet without affecting anterior leaflet motion. The excursion of the anterior leaflet edge from maximally open to fully closed was not different between the groups (control, 13+/-2 mm; Duran 13+/-1 mm; Physio ring, 14+/-1 mm; p > 0.05), but posterior leaflet edge excursion was restricted (control, 7.4+/-0.4 mm; 2.3+/-0.3 mm [p < 0.001]; Physio, 2.7+/-0.2 mm [p < 0.001]) by both rings. CONCLUSIONS Mitral annuloplasty with either ring type markedly reduced the mobility of the central posterior leaflet in normal ovine hearts such that valve closure became essentially a single (anterior) leaflet process with the frozen posterior leaflet serving only as a buttress for closing.

Limitations of comparing left ventricular volumes by two dimensional echocardiography, myocardial markers and cineangiography

Abstract Measurement of left ventricular volume at end-diastole or end-systole with both two dimensional echocardiography and either Cineangiography or radionuclide scans, not recorded simultaneously, has shown large echocardiographic underestimation of volumes even in normal ventricles. In this study fluoroscopic and two dimensional echocardiographic recordings were obtained in 18 patients with abnormal wall motion and previously implanted myocardial markers. The echocardiographic values for volume and those derived from myocardial markers correlated well (r = 0.87), and there were no statistically significant differences in values obtained with the two methods at end-diastole or end-systole. The ejection fractions obtained with two dimensional echocardiography (mean ± standard deviation 46 ± 7 percent) and with fluoroscopic recording of the markers (41 ± 9 npercent) did not differ statistically. These results were compared with those in another 18 patients (nine with abnormal wall motion) having two dimensional echocardiography within 24 hours of a 30 ° right anterior oblique contrast left ventriculogram. Again, two dimensional echocardiographic ventricular volume correlated well with the angiographic volume (r = 0.85), although echocardiographic end-diastolic volume was consistently 20 percent less than angiographic end-diastolic volume (p Probable reasons for the lack of severe underestimation of volume with echocardiography even in very abnormal ventricles, relative to that demonstrated in prior reports, include improvements in ultrasonic beam width, tracing method, transducer position and scan plane orientation within the ventricle. In addition, the possible effects of angiographic dye in the ventricular trabeculae are discussed and the effect of simultaneous studies by two different methods are compared.

Experimental evaluation of different chordal preservation methods during mitral valve replacement

During chordal-sparing mitral valve replacement (MVR), some recommend anatomic reattachment of the anterior leaflet chordae to the anterior annulus; others advocate shifting the chordae to the posterior annulus. To compare the results of these techniques with those of conventional MVR (total chordal excision), 21 dogs were studied 5 to 12 days after implantation of tantalum markers to measure left ventricular volume and geometry. One to 3 weeks later, animals underwent conventional MVR (n = 7) or chordal-sparing MVR with either anterior chordal reattachment (n = 7) or posterior transposition (n = 7). Contractility was assessed using physiologic volume intercepts for end-systolic elastance, preload recruitable stroke work, and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume. The physiologic intercept for end-systolic elastance did not change after anterior or posterior MVR, but increased from 60 +/- 14 mL before MVR to 72 +/- 17 mL with conventional MVR (p < 0.002), indicating impaired left ventricular contractility. Similarly, the physiologic intercept for preload recruitable stroke work and the relationship of the maximum rate of change of left ventricular pressure to the end-diastolic volume increased 22% +/- 13% and 28% +/- 13%, respectively, after conventional MVR, but neither changed after anterior or posterior MVR. Although the end-diastolic pressure-volume relationship did not change with either chordal-sparing technique, its slope increased 98% +/- 73% after conventional MVR (p < 0.008). Thus, although chordal preservation maintained better systolic and diastolic function, there was no substantial difference between the results of the anterior and posterior chordal-sparing techniques in this model.

Importance of Mitral Valve Second-Order Chordae for Left Ventricular Geometry, Wall Thickening Mechanics, and Global Systolic Function

Background—Mitral valvular–ventricular continuity is important for left ventricular (LV) systolic function, but the specific contributions of the anterior leaflet second-order “strut” chordae are unknown. Methods and Results—Eight sheep had radiopaque markers implanted to silhouette the LV, annulus, and papillary muscles (PMs); 3 transmural bead columns were inserted into the mid-lateral wall between the PMs. The strut chordae were encircled with exteriorized wire snares. Three-dimensional marker images and hemodynamic data were acquired before and after chordal cutting. Preload recruitable stroke work (PRSW) and end-systolic elastance (Ees) were calculated to assess global LV systolic function (n=7). Transmural strains were measured from bead displacements (n=4). Chordal cutting caused global LV dysfunction: Ees (1.48±1.12 versus 0.98±1.30 mm Hg/mL, P=0.04) and PRSW (69±16 versus 60±15 mm Hg, P=0.03) decreased. Although heart rate and time from ED to ES were unchanged, time of mid-ejection was delayed (125±18 versus 136±19 ms, P=0.01). Globally, the LV apex and posterior PM tip were displaced away from the fibrous annulus and LV base-apex length increased at end-diastole and end-systole (all +1 mm, P<0.05). Locally, subendocardial end-diastolic strains occurred: Longitudinal strain (E22) 0.030±0.013 and radial thickening (E33) 0.081±0.041 (both P<0.05 versus zero). Subendocardial systolic shear strains were also perturbed: Circumferential-longitudinal “micro-torsion” (E12) (0.099±0.035 versus 0.075±0.025) and circumferential radial shear (E13) (0.084±0.023 versus 0.039±0.008, both P<0.05). Conclusion—Cutting second-order chords altered LV geometry, remodeled the myocardium between the PMs, perturbed local systolic strain patterns affecting micro-torsion and wall-thickening, and caused global systolic dysfunction, demonstrating the importance of these chordae for LV structure and function.