Marc R. Moon

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

BACKGROUNDnLeft 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.nnnMETHODS AND RESULTSnSix 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.nnnCONCLUSIONSnIn 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.

Treatment of endocarditis with valve replacement: the question of tissue versus mechanical prosthesis

BACKGROUNDnIt remains unknown whether there is any important clinical advantage to the use of either a bioprosthetic or mechanical valve for patients with native or prosthetic valve endocarditis.nnnMETHODSnBetween 1964 and 1995, 306 patients underwent valve replacement for left-sided native (209 patients) or prosthetic (97 patients) valve endocarditis. Mechanical valves were implanted in 65 patients, bioprostheses in 221 patients, and homografts in 20 patients.nnnRESULTSnOperative mortality was 18+/-2% and was independent of replacement valve type (p > 0.74). Long-term survival was superior for patients with native valve endocarditis (44+/-5% at 20 years) compared with those with prosthetic valve endocarditis (16+/-7% at 20 years) (p < 0.003). Survival was independent of valve type (p > 0.27). The long-term freedom from reoperation for patients who received a biologic valve who were younger than 60 years of age was low (51+/-5% at 10 years, 19+/-6% at 15 years). For patients older than 60 years, however, freedom from reoperation with a biological valve (84+/-7% at 15 years) was similar to that for all patients with mechanical valves (74+/-9% at 15 years) (p > 0.64).nnnCONCLUSIONSnMechanical valves are most suitable for younger patients with native valve endocarditis; however, tissue valves are acceptable for patients greater than 60 years of age with native or prosthetic valve infections and for selected younger patients with prosthetic valve infections because of their limited life expectancy.

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.

Surgical Treatment of Endocarditis

Since early investigators first suggested that the treatment of endocarditis should include valve replacement for infections not readily controlled with medical therapy alone, the role of surgery has become expanded, yet refined, to improve the outcome of patients with this potentially fatal disease. Innovative surgical techniques have also been developed in an effort to improve the results of surgical treatment for complex sequelae of invasive infections. This article examines the current indications for surgical intervention, compares the various surgical options, and assesses the expected short-and long-term outcome after valve replacement for patients with native valve or prosthetic valve endocarditis.

Pilot study of the efficacy of a thrombin inhibitor for use during cardiopulmonary bypass

Heparin is normally used for anticoagulation during cardiopulmonary bypass (CPB), but its use is contraindicated in patients with a history of heparin-induced thrombocytopenia, heparin-provoked thrombosis, or both. Heparin therapy can also be ineffective due to heparin resistance. A short-acting, oligonucleotide-based thrombin inhibitor (thrombin aptamer) may potentially serve as a substitute for heparin in these and other clinical situations. We tested a novel thrombin aptamer in a canine CPB pilot study to determine its anticoagulant efficacy, the resultant changes in coagulation variables, and the aptamers clearance mechanisms and pharmacokinetics. Seven dogs were studied initially: Four received varied doses of the aptamer (to establish the pharmacokinetic profile) and 3 received heparin. Subsequently, 4 other dogs underwent CPB, receiving a constant infusion of the aptamer before CPB (to characterize the baseline coagulation status), with partial CPB and hemodilution, during 60 minutes of total CPB, and, finally, after a 2-hour recovery period. At a 0.5 mg.kg-1.min-1 dose, the activated clotting time rose with aptamer infusion from 106 +/- 12 seconds to 187 +/- 8 seconds (+/- 1 standard deviation) (p = 0.014), increased further with hemodilution (to 259 +/- 41 seconds; p = 0.017), and was even more prolonged during total CPB (> 1,500 seconds; p < 0.001). This later increase in the activated clotting time paralleled a rise in the plasma concentration of the thrombin aptamer during total CPB, as determined by high-performance liquid chromatography.(ABSTRACT TRUNCATED AT 250 WORDS)

Simultaneous abdominal aortic replacement and thoracic stent-graft placement for multilevel aortic disease

PURPOSEnPatients with aneurysmal disease involving both the descending thoracic and abdominal aorta have historically required simultaneous or sequential conventional operations, but the morbidity rate is high with either approach in these patients, who often exhibit coexisting cardiopulmonary disease. Transluminally placed endovascular grafts have recently been developed for repair of aortic aneurysms, and we have implemented these techniques to eliminate the need for a thoracotomy in patients with multilevel aortic disease.nnnMETHODSnSince January 1994, 18 patients have undergone conventional abdominal aortic replacement with endovascular stent-graft placement into the descending thoracic aorta under fluoroscopic guidance through a 10 mm Dacron side limb off the abdominal graft. Abdominal aortic replacement required a tube graft in eight patients and bifurcated grafts in 10 patients. Thoracic stent-grafts (custom fabricated, woven Dacron covered, self-expandable stents) averaged 12.2 +/- 4.2 cm (mean +/- SD) in length.nnnRESULTSnOne patient died, resulting in a hospital mortality rate of 6%. No patients required further surgical intervention to treat their aortic disease. Seventeen patients (94%) are currently well 14 +/- 8 months after surgery (range, 3 to 29 months) with completely excluded thoracic aortic disease, no stent migration, and no change in stent configuration documented by serial radiologic examinations.nnnCONCLUSIONSnSimultaneous abdominal aortic replacement and deployment of a thoracic stent-graft can safely exclude multilevel aortic aneurysmal disease and may be a valuable treatment option for these otherwise high-risk patients.

Right ventricular dynamics during left ventricular assistance in closed-chest dogs.

To determine the effects of left ventricular assist device (LVAD) support on global right ventricular (RV) systolic mechanics, 8 closed-chest, conscious, sedated dogs were studied after placement of an LVAD (left ventricle to femoral artery bypass) and implantation of 27 tantalum markers into the left ventricular and RV walls for computation of biventricular volumes and geometry. Biplane cinefluoroscopic marker images and hemodynamic parameters were recorded during transient vena caval occlusion at various levels of LVAD support. Right ventricular contractility was assessed using end-systolic elastance and preload recruitable stroke work, and the myocardial (pump) efficiency of converting mechanical energy to external work (stroke work/total pressure-volume area) was calculated. With full LVAD support, RV end-diastolic volume increased from 60 +/- 15 to 62 +/- 17 mL (p < 0.002), pulmonary artery input impedance decreased from 940 +/- 636 to 587 +/- 347 dyne.s/cm5 (p < 0.007), and measurement of RV and left ventricular septal-free wall dimensions demonstrated a significant leftward septal shift (p < 0.0005). Global RV end-systolic elastance and preload recruitable stroke work decreased from 2.4 +/- 1.0 to 1.7 +/- 0.7 mm Hg/mL (p < 0.004) and 14.1 +/- 3.3 to 12.1 +/- 3.9 mm Hg (p < 0.02), respectively; however, RV power output and myocardial efficiency did not change significantly (p > 0.74 and p > 0.33, respectively). Therefore, during LVAD support, global RV contractility is impaired with leftward septal shifting, but RV myocardial efficiency and power output are maintained through a decrease in RV afterload and an increase in RV preload.

Heart-lung versus double-lung transplantation for suppurative lung disease.

OBJECTIVEnThe purpose of this study was to compare outcomes after heart-lung or double-lung transplantation in patients undergoing transplantation because of end-stage suppurative lung disease.nnnMETHODSnWe reviewed our experience in patients with cystic fibrosis or bronchiectasis who had heart-lung or double-lung transplantation between January 1988 and September 1997. Twenty-three patients (14 male, 21 cystic fibrosis) had heart-lung transplantation and 24 patients (8 male, 19 cystic fibrosis) had double-lung transplantation. There were no statistically significant differences between the groups in age, weight, preoperative creatinine level, cytomegalovirus status, maintenance immunosuppression, or donor demographics. Patients received induction therapy with monoclonal (OKT3) or polyclonal (rabbit anti-thymocyte globulin) antibody.nnnRESULTSnSixteen of 24 patients had double-lung transplantation after 1994 whereas 13 of 22 patients had heart-lung transplantation before 1991, allowing longer follow-up for the heart-lung group. Mean waiting times for transplantation were 270 +/- 245 days (heart-lung) and 361 +/- 229 days (double-lung; P =.20). The 1-, 3-, and 5-year actuarial survival figures were respectively 86%, 82%, and 65% (heart-lung) and 96%, 75%, and unavailable (double-lung; P = no significant difference). The 1-, 3-, and 5-year rates of freedom from obliterative bronchiolitis were respectively 77%, 61%, and 45% (heart-lung) and 86%, 78%, and unavailable (double-lung; P = no significant difference). Linearized overall infection rates (events/100 patient-days) were 2.05 +/- 0.33 (heart-lung) and 2.34 +/- 0.34 (double-lung; P = NS) at 3 months. Thirty-day survival was 100% (heart-lung) and 96% (double-lung). There were 7 late deaths among heart-lung recipients (3 obliterative bronchiolitis, 2 infection, 0 graft coronary artery disease, 2 other) whereas 2 late deaths related to obliterative bronchiolitis occurred in double-lung recipients. Graft coronary artery disease (all stenoses < 50%) affected 15% of heart-lung survivors, whereas 3 double-lung recipients (12.5%) required either bronchial dilatation or stenting.nnnCONCLUSIONnHeart-lung and double-lung transplantation provide similar palliation for patients with end-stage suppurative lung disease. Therefore double-lung transplantation should be the preferred operation for most patients with end-stage suppurative lung disease.

Effects of mitral valve replacement on regional left ventricular systolic strain

BACKGROUNDnMitral valve replacement (MVR) with chordal excision impairs left ventricular (LV) systolic function, but the responsible mechanisms remain incompletely characterized. Loss of normal annular-papillary continuity also adversely affects LV torsional deformation, possibly due to changes in myocardial fiber contraction pattern.nnnMETHODSnTwenty-seven dogs underwent insertion of LV myocardial markers and a sham procedure (cardiopulmonary bypass, no MVR, n = 6), conventional MVR with chordae tendineae excision (n = 7), or chordal-sparing MVR with reattachment of the anterior leaflet chordae to the anterior annulus (n = 7) or to the posterior annulus (n = 7). In the anterior, lateral, posterior, and septal LV regions, linear chords were constructed from each regions central marker to its surrounding markers. Percent systolic shortening (regional LV strain) was calculated for each chord, and the chords were assigned to one of four angular groups: I, left-handed oblique (subepicardial fiber direction); II, circumferential (midwall); III, right-handed oblique (subendocardial); or IV, longitudinal. Regional LV strain data were compared before and after MVR.nnnRESULTSnSham and anterior chordal-sparing MVR had minimal effects on regional LV strain. With posterior chordal-sparing MVR: anteriorly, left-oblique (I) strain fell (31%, p<0.05), as did circumferential (II) and right-oblique (III) strains (by 49% and 51%, respectively; p<0.01). Laterally, left-oblique (I) strain fell by 36% (p<0.05), as did longitudinal (IV) strain (54% decline, p<0.01). Conventional MVR with chordal excision disrupted regional fiber shortening diffusely, affecting oblique fibers (I and III) in the anterior and septal regions and impairing longitudinal (IV) strain in all regions (45% to 68% fall, p<0.05).nnnCONCLUSIONSnSham and anterior chordal-sparing MVR did not substantially alter regional LV strain; however, loss of normal anatomic valvular-ventricular integrity (conventional MVR) or posterior chordal-sparing MVR resulted in pronounced alterations in LV strain, most notably in the longitudinal and oblique fiber directions. These findings demonstrate that the deleterious effects of chordal excision are associated with perturbed internal myocardial systolic deformation, which suggests that chordal disruption distorts myofiber architecture or regional systolic loading.