Preserved left ventricular function during supine exercise in patients after orthotopic cardiac transplantation.

Cardiac denervation may affect cardiovascular responses during exercise in patients after orthotopic cardiac transplantation. In 17 such patients, haemodynamic responses and left ventricular function were examined by radionuclide ventriculography during and after supine exercise, at an average of 17.1 +/- 2.6 months after surgery. Data were also obtained during 'volume loading' brought about by leg elevation before exercise. Results were compared with those of six normal controls. At rest, heart rate was significantly faster among transplant patients than among controls (P less than 0.0003). No significant inter-group differences in changes in cardiovascular parameters were found between the two groups during leg elevation. During exercise, heart rate in transplant patients rose at a significantly slower rate than controls (P = 0.0001), but similar increases in ejection fraction, stroke volume and cardiac output were observed among transplant patients and controls. Decline in heart rate (P = 0.0001), ejection fraction (P = 0.0007) and cardiac output (P = 0.0001) was significantly slower in transplant patients during recovery. Although there were differences in rates of increases in heart rate between transplant patients and controls during supine exercise, there were no inter-group differences in increases in cardiac output and ejection fraction and changes in haemodynamic responses and left ventricular volumes.     

Determinants of left ventricular function one year after cardiac transplantation.

Left ventricular systolic function was assessed by radionuclide angiography in 107 consecutive transplant recipients who were alive one year after operation. Mean (SEM) ejection fraction was 62.4 (4.6) at rest and 68.8 (5.4) on exercise. The influence of donor-related factors (donor age and sex, ischaemia time), recipient-related factors (recipient age and sex, frequency of acute rejection), type of immunosuppression (cyclosporin/azathioprine or prednisolone/azathioprine), and frequency of hypertension on left ventricular function one year after operation was examined by univariate and multivariate analysis. There was a close association both at rest and on exercise between a higher ejection fraction and treatment with cyclosporin/azathioprine. There was a trend for lower donor and recipient age, shorter ischaemia time, and fewer rejection episodes to be associated with better left ventricular function, but this was not statistically significant. Left ventricular systolic function was well maintained in most patients a year after cardiac transplantation. The type of immunosuppression used had a strong influence on the left ventricular systolic function of the transplanted heart.     

Determinants of left ventricular function one year after cardiac transplantation

Left ventricular systolic function was assessed by radionuclide angiography in 107 consecutive transplant recipients who were alive one year after operation. Mean (SEM) ejection fraction was 62.4 (4.6) at rest and 68.8 (5.4) on exercise. The influence of donor-related factors (donor age and sex, ischaemia time), recipient-related factors (recipient age and sex, frequency of acute rejection), type of immunosuppression (cyclosporin/azathioprine or prednisolone/azathioprine), and frequency of hypertension on left ventricular function one year after operation was examined by univariate and multivariate analysis. There was a close association both at rest and on exercise between a higher ejection fraction and treatment with cyclosporin/azathioprine. There was a trend for lower donor and recipient age, shorter ischaemia time, and fewer rejection episodes to be associated with better left ventricular function, but this was not statistically significant. Left ventricular systolic function was well maintained in most patients a year after cardiac transplantation. The type of immunosuppression used had a strong influence on the left ventricular systolic function of the transplanted heart.     

Evaluation by Doppler echocardiography of left ventricular diastolic function in acute graft rejection after heart transplantation

In order to study abnormalities of left ventricular diastolic function (LVDF) in heart transplant patients and their possible association with graft rejection, 21 patients who had recently undergone orthotopic heart transplantation were evaluated prospectively, on the day of endomyocardial biopsy, by pulsed and continuous Doppler echocardiography (DEC). Investigation of the LVDF consisted of pulsed DEC of the mitral valve in apical projection (4 cavities) with measurement of isovolumetric relaxation time (IVR), peak velocity of rapid ventricular filling (E), peak velocity of graft atrial contraction (A) and transmitral gradient decrease half-time (mitral T1/2). Each patients had 5 DEC examinations on average over a 2-month period. In patients with subsevere to severe rejection mitral T1/2 decreased significantly from 76.46 +/- 11.6 ms in the absence of rejection to 47 +/- 13.7 ms during rejection (P less than 0.001). When mitral T1/2 decreased by 25 p. 100 or more between two successive DEC, rejection was present in 89 p. 100 of the cases. It is concluded that Doppler echocardiographic studies of left ventricular diastolic function provide useful information in the follow-up of heart transplant recipients and offer hopes, in a not too distant future, of non-invasive detection of cardiac graft rejection.     

Evaluation of a noninvasive index of global ventricular function to predict rejection after pediatric cardiac transplantation

A Doppler myocardial performance index, defined as the sum of the isovolumetric contraction and relaxation time divided by the ejection time (ICT + IRT/ET), reflects global cardiac function, and when applied to the left ventricle, may serve as a predictor of moderate rejection in pediatric cardiac transplant patients.     

Echocardiographic signs of cardiac rejection during the first week after cardiac transplantation

The early recognition of acute rejection after heart transplantation remains an important clinical problem. In this study we explored the value of echo-Doppler techniques to identify the rejection during the first week after cardiac transplantation. The study included 22 patients with an average age of 48 +/- 9 years. Ultrasonic measurements were obtained by 2-dimensional 84 degrees phased array sector scanner with pulsed Doppler incorporated. The stroke index (SI), the peak outflow blood velocity pulsed (POBVP), the peak outflow blood acceleration pulsed (POBAP), the peak flow velocity in early diastole (PFVE), the peak flow velocity during atrial systole (PFVA), the PFVA/PFVE ratio, the mitral valve pressure half-time (PHT) and the fractional shortening (FS) were calculated. On the seventh day after transplantation, a percutaneous right ventricular endomyocardial biopsy was systematically performed. For the entire group, the SI, PHT and the FS relation were not significantly influenced during the week of evaluation. The POBVP and the POBAP transiently decreased but returned to baseline on the seventh day. An increment in the PFVA/PFVE ratio was observed in 4 patients, and acute allograft rejection was documented in 3 of them. On day 7 after transplantation, PFVA and PFVA/PFVE were significantly higher in patients with rejection. No patient with normal PFVA/PFVE ratio had allograft rejection. No patient with rejection showed signs of altered systolic function as measured by SI, POBVP, POBAP and FS. These data therefore indicate that the assessment of the diastolic function using Doppler techniques (PFVA/PFVE) can be helpful to detect signs of acute allograft rejection occurring early after heart transplant.     

Changes in left ventricular function during chemotherapy with doxorubicin

The authors investigated by echocardiography changes of left ventricular function in 79 patients with non-Hodgkin lymphoma or Hodgkin's disease who were treated by chemotherapy containing doxorubicin. In 22% patients they diagnosed during treatment a significant gradual decline of the left ventricular ejection fraction (change > 10% or a drop of EF below 50%) after a cumulative dose of 185 +/- 52 mg/m2 doxorubicin (median 200 mg/m2). Changes of the ejection fraction were at the expense of an increasing endsystolic left ventricular volume. These changes correlated closely with the increase of endsystolic stress of the left ventricular wall (r = -0.87). After administration of a cumulative doxorubicin dose of 100 mg/m2 a significant deterioration of indicators of diastolic filling of the left ventricle occurred--of the isovolumic relaxation period (IRP) and deceleration time (DT). The contribution of these early changes of diastolic function of the left ventricle for assessment of the risk of development of systolic dysfunction is not unequivocal. Prolongation of IRP > 12% as compared with the baseline value and at the same time above 95 ms had a 50% sensitivity, 50% specificity, a 26% positive prediction value a 74% negative prediction value and 50% diagnostic accuracy, change of DT > 13%, and at the same time prolongation above 200 ms had a 47% sensitivity 55% specificity, a 22% positive prediction value, a 78% negative prediction value and a 53% diagnostic accuracy. The authors found a significant relationship between the assessed changes of left ventricular function and clinical and haemodynamic indicators. Only the patients' age correlated significantly with IRP and DT values. Changes of the left ventricular ejection fraction were not associated with clinical signs of cardiac failure, they did not call for cardiological intervention and did not affect the course of chemotherapy. Contrary to some statements in the literature, the authors did not consider the described functional changes as sufficient to justify interference with chemotherapy. On the other hand, their importance for the development of late sequelae of chemotherapy with anthracyclines in adult patients must be based on long-term prospective follow-up.     

Arteritis in cardiac rejection after transplantation

During a 4-year experience with cardiac transplantation, 33 hearts were obtained by autopsy or surgical resection for retransplantation. Arteritis was a feature common to all rejected hearts (14 of 14), but was absent in explanted hearts without rejection (0 of 19) (p = 0.001). Monitoring of acute cardiac rejection by endomyocardial biopsy (863 biopsies) was also reviewed, with special reference to the incidence of arteritis. Among the 16 patients with arteritis on 1 or more biopsies, 44% (7 patients, confidence limits 29 to 60%) suffered fatal rejection or underwent retransplantation because of irreversible rejection. Arteritis was seen in the small vessels obtained by endomyocardial biopsy in 4 of 5 persons who underwent biopsy within 3 days of death or retransplantation due to rejection and on none of the 6 persons who underwent biopsy within 3 days of death or retransplantation for causes other than rejection. Thus, arteritis is an important indicator for severe acute rejection, and although often reversible, may identify patients at higher risk for fatal rejection. Arteritis occurred in transplanted hearts subjected to varying combinations of cyclosporine, azathioprine and steroid therapy and could not be correlated with any drug regimen.     

Treating humoral rejection after cardiac transplantation

Whereas effective strategies are available to treat acute cellular cardiac rejection, humoral rejection, also called vascular or antibody-mediated rejection, is more difficult to manage. Antibody-mediated (non-cellular) rejections (AMR) are rare and few successfully treated cases have been described in the literature. We report on a female patient, diagnosed with humoral rejection, leading to severe ventricular dysfunction and haemodynamic compromise, two months after transplantation. The patient received a combination therapy, consisting of plasmapheresis and immunoglobulins, which resulted in complete resolution of immunohistochemical signs of AMR. In this report, we will overview AMR and discuss several treatment modalities.     

Deficient acceleration of left ventricular relaxation during exercise after heart transplantation.

BACKGROUND. The exercise-induced rise in left ventricular filling pressures after cardiac transplantation is considered to be the result of a blunted heart rate response, of elevated venous return, and of unfavorable passive late-diastolic properties of the cardiac allograft. In contrast to passive late-diastolic left ventricular properties, the effect of left ventricular relaxation on the exercise-induced rise in left ventricular filling pressures of the cardiac allograft has not yet been studied. In the present study, the response of left ventricular relaxation to exercise was investigated in transplant recipients and compared with left ventricular relaxation observed in normal control subjects exercised to the same heart rate. Moreover, the response of left ventricular relaxation of the cardiac allograft to beta-adrenoreceptor stimulation, to reduced left ventricular afterload, and to increased myocardial activator calcium was investigated by infusion of dobutamine and of nitroprusside and by postextrasystolic potentiation. METHODS AND RESULTS. Twenty-seven transplant recipients were studied 1 year (n = 17), 2 years (n = 7), 3 years (n = 2), and 4 years (n = 1) after transplantation. All patients were free of rejection and of significant graft atherosclerosis at the time of study. Tip-micromanometer left ventricular pressure recordings and cardiac hemodynamics were obtained at rest, during supine bicycle exercise stress testing (n = 27), during dobutamine infusion at a heart rate matching the heart rate at peak exercise (n = 8), during nitroprusside infusion (n = 9), and after postextrasystolic potentiation (n = 10). Tip-micromanometer left ventricular pressure recordings were also obtained in a normal control group (n = 9) at rest and during supine bicycle exercise stress testing to a heart rate, which matched the heart rate of the transplant recipient group at peak exercise. Left ventricular relaxation rate was measured by calculation of a time constant of left ventricular pressure decay (T) derived from an exponential curve fit to the digitized tip-micromanometer left ventricular pressure signal. In the transplant recipients, exercise abbreviated T from 43 +/- 6 to 40 +/- 8 msec (p less than 0.01) and caused a rise of left ventricular minimum diastolic pressure (LVMDP) from 5 +/- 2 to 9 +/- 6 mm Hg (p less than 0.001). In normal control subjects, exercise induced a 2.5 times larger abbreviation of T (from 42 +/- 7 to 34 +/- 6 msec; p less than 0.001) and a small drop in LVMDP from 5 +/- 2 to 4 +/- 3 mm Hg (p less than 0.05). In the transplant recipients, the change in T (delta T) from rest to exercise was variable ranging from an abbreviation, as observed in normal controls, to a prolongation and was significantly correlated with the change in RR interval (delta RR) and the change in left ventricular end-diastolic pressure (delta LVEDP) (delta T = 0.068 delta RR + 0.58 delta LVEDP-2.2; r = 0.76; p less than 0.001). In a first subset of transplant recipients (n = 8), dobutamine infusion resulted in a heart rate equal to the heart rate at peak exercise, a left ventricular end-diastolic pressure (8 +/- 7 mm Hg) lower than at peak exercise (22 +/- 6 mm Hg; p less than 0.05) and a T value (32 +/- 9 msec), which was shorter than both resting value (44 +/- 5 msec; p less than 0.005) and value observed at peak exercise (40 +/- 8 msec; p less than 0.01). In a second subset of transplant recipients (n = 9), nitroprusside infusion and postextrasystolic potentiation resulted in a significant prolongation of T from 41 +/- 7 to 56 +/- 10 msec (p less than 0.05) and a characteristic negative dP/dt upstroke pattern with downward convexity as previously observed in left ventricular hypertrophy. CONCLUSIONS. Exercise after cardiac transplantation resulted in a smaller acceleration of left ventricular relaxation than in a normal control group exercised to the same heart rate...     

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.     

Time course of left ventricular function after cardiac denervation in conscious dogs.

The time course of left ventricular (LV) function was compared in normal (N) and cardiac-denervated (CD) dogs over an 8-week period after instrumentation with solid-state LV pressure gauges and three pairs of ultrasonic crystals to measure LV long and short axes and wall thickness. Baseline LV systolic, end-systolic, and end-diastolic pressures did not differ in N and CD dogs. Heart rate was higher (p less than 0.01) and LV dP/dt was lower (p less than 0.05) in CD dogs. LV short-axis shortening, shortening fraction, velocity of circumferential fiber shortening, and ejection fraction were consistently lower (p less than 0.01) in CD dogs. With angiotensin II to increase LV afterload, relations of LV short-axis shortening, shortening fraction, velocity of circumferential fiber shortening, and ejection fraction to average LV systolic wall stress were shifted downward (p less than 0.01) in CD dogs at 2, 4, and 8 weeks. Relations of LV short-axis shortening to LV end-diastolic wall stress also differed (p less than 0.01) in N and CD dogs. Ganglionic blockade abolished differences in LV function between N and CD dogs during elevated LV systolic wall stress with angiotensin II. Thus, in conscious dogs, cardiac denervation results in a sustained reduction of LV function over a wide range of ventricular loading conditions.     

Changes in left ventricular morphology and function after mitral valve surgery

Degenerative mitral valve disease is the leading cause of mitral regurgitation in North America. Surgical intervention has hinged on the symptoms and ventricular changes that develop as compensatory ventricular remodeling occurs. In the present study, we sought to characterize the temporal response of left ventricular (LV) morphology and function to mitral valve surgery for degenerative disease and to identify the preoperative factors that influence reverse remodeling. From 1986 to 2007, 2,778 patients with isolated degenerative mitral valve disease underwent valve repair (n = 2,607 [94%]) or replacement (n = 171 [6%]) and had ≥1 postoperative transthoracic echocardiogram; 5,336 transthoracic echocardiograms were available for analysis. Multivariate longitudinal repeated-measures analysis was performed to identify the factors associated with reverse remodeling. The LV dimensions decreased in the first year after surgery (end-diastolic from 5.7 ± 0.80 to 4.9 ± 1.4 cm; end-systolic from 3.4 ± 0.71 to 3.1 ± 1.4 cm). The LV mass index decreased from 139 ± 44 to 112 ± 73 g/m(2). The reduction in LV hypertrophy was less pronounced in patients with greater preoperative left heart enlargement (p <0.0001) and a greater preoperative LV mass (p <0.0001). The postoperative LV ejection fraction initially decreased from 58 ± 7.0% to 53 ± 20%, increased slightly during the first postoperative year, and was negatively influenced by preoperative heart failure symptoms (p <0.0001) and a lower preoperative LV ejection fraction (p <0.0001). The risk-adjusted response of LV morphology and function to valve repair and replacement was similar (p >0.2). In conclusion, a positive response toward normalization of LV morphology and function after mitral valve surgery is greatest in the first year. The best response occurs when surgery is performed before left heart dilation, LV hypertrophy, or LV dysfunction develop.     

Right ventricular failure after cardiac surgery

Right ventricular (RV) failure remains a major problem in cardiac surgery, particularly in the setting of heart transplantation and following institution of left ventricular support. Experimental studies have shown that RV function is derived from 2 sources: the free wall of the RV and the interventricular septum. Management of RV failure involves not only decreasing RV afterload, but also optimizing both contributions to RV function, which is best achieved by optimizing developed systemic pressure. Techniques for managing the pulmonary circulation and strategies for optimizing RV function in various clinical settings are presented.     

Doppler cardiac output and left ventricular performance after cardiac surgery. Pulsed Doppler ascending aorta and pulmonary blood flows and left ventricular function using implanted microprobes.

We have developed novel implantable Doppler microprobes to monitor beat-by-beat stroke volume and cardiac output (CO) after cardiac surgery. In 11 adults undergoing either coronary artery bypass grafting (n = 6) or valve replacement (n = 5), Doppler microprobes were implanted on the ascending aorta or the main pulmonary artery to measure aortic blood flow (ABF) or pulmonary artery blood flow (PBF). The diameters of both vessels were determined before surgery using two-dimensional echocardiography. Stroke volume was obtained from velocity tracings measured by a 4-MHz zero-crossing pulsed Doppler flowmeter. Simultaneous measurements of Doppler and thermodilution CO (TDCO) were compared. We found the following: ABF = 1.03 TDCO - 0.22 L/min (r = 0.89); while PBF = 0.69 TDCO - 1.24 L/min (r = 0.75). Furthermore, peak flow velocity and maximum acceleration of blood in the ascending aorta were measured after inotropic stimulation with dobutamine; both values increased significantly from control values (25.2 +/- 6.1 percent and 44.6 +/- 8.6 percent, respectively, at 7.5 micrograms/kg/min). We conclude that implanted aortic Doppler microprobes provide a sensitive and reliable method to measure aortic blood flow velocity after surgery and then allow monitoring of stroke volume and CO and analysis of left ventricular function after cardiac surgery.     

Right ventricular function following cardiac resynchronization therapy

The effect of cardiac resynchronization therapy (CRT) on right ventricular (RV) function has not been well described. The purpose of this study was to use tissue Doppler imaging to assess changes in RV function after CRT. Thirty-five patients with heart failure (age 65 +/- 10 years; 26 men) who underwent color tissue Doppler imaging of the right ventricle both immediately before CRT and >3 months (mean 6 +/- 3) after were studied. Myocardial systolic velocity was measured at the tricuspid annulus and basal and midventricular segments of the right ventricle free wall and averaged to obtain a measure of global RV function (RV S(m)). Left ventricular ejection fraction was also measured using biplane Simpson's method before and after CRT. RV S(m) significantly improved after CRT (5.4 +/- 1.9 to 7.1 +/- 2.6 cm/s; p <0.001), as did left ventricular ejection fraction (26 +/- 6% to 34 +/- 10%; p <0.001). Twenty-one of 35 patients (60%) showed an increase in RV S(m) > or =1 cm/s, with an increase > or =2 cm/s in 13 of those patients (37%). Improvement was seen in both ischemic and nonischemic patients and was independent of improvement in left ventricular ejection fraction and baseline left ventricular dyssynchrony. In conclusion, CRT resulted in improved RV function measured as RV S(m). CRT had beneficial effects on RV function independent of improvement in left ventricular ejection fraction.     

Assessment of left ventricular function by cardiac ultrasound.

Our understanding of the physical underpinnings of the assessment of cardiac function is becoming increasingly sophisticated. Recent developments in cardiac ultrasound permit exploitation of many of these newer physical concepts with current echocardiographic machines. This review will first focus on the current approach to the assessment of cardiovascular hemodynamics by cardiac ultrasound. The next focus will be the assessment of global cardiac mechanics in systole and diastole. Finally, relationships between the cardiac structure and regional myocardial function, and the way regional function can be quantified by ultrasound, will be presented. This review also discusses the clinical impact of echocardiography and its future directions and developments.