C4d analysis in endomyocardial biopsies of heart transplant patients: is there a correlation with hemodynamic data?

BACKGROUND: Endomyocardial biopsy (EMB) is the gold standard for immunologic follow-up to detect acute cellular rejection after cardiac transplantation. Conversely, protocols for the diagnosis and treatment of antibody-mediated rejection (AMR) are not well defined. Histologically, AMR is diagnosed by the presence of capillary damage associated with complement activation. The aim of this study was to correlate C4d expression of activated complement in EMB with hemodynamic compromise upon right heart catheterization. METHODS: Heart transplant patients underwent hemodynamic and histologic follow-up with EMB and right heart catheterization between January 2008 and December 2009 for a total of 491 procedures. The cardiac biopsy was evaluated for acute cellular and AMR by means of the presence of the C4d complement fraction. The histologic results were compared with hemodynamic data registered during right heart catheterization. RESULTS: Comparison of the hemodynamic data of subjects with versus without C4d positivity showed no significant difference. Furthermore, there was no significant difference comparing patients with versus without C4d positivity in the absence of significant acute cellular rejection episodes. (C4d-/ACR- vs C4d+/ACR-). The variation of each single hemodynamic parameter from its basal value (defined as the mean value in case of C4d-/ACR-) seemed to not be influenced by the presence of C4d+. CONCLUSIONS: In our experience, C4d has been routinely evaluated in the majority of EMBs. We could not demonstrate a significant correlation of C4d positivity with hemodynamic compromise. These findings suggest that significant allograft dysfunction is not related to C4d positivity. Therefore, the diagnosis of AMR is difficult to establish, because allograft dysfunction is 1 of the 3 fundamental criteria.

Results with cyclosporine monotherapy in long-term cardiac transplant recipients.

BACKGROUND: Triple therapy is the gold standard after heart transplantation while few reports have described experiences with cyclosporine monotherapy (CM). We have analyzed our experience with CM in long-term heart transplant recipients, surviving >5 years. METHODS: Of the 219 patients transplanted between January 1990 and December 1998, 143 survived >5 years (mean age, 49.6 +/- 10.4). There were 124 (86.7%) male subjects. Matching patients respect to follow-up length, we obtained 2 groups: group A of 41 patients on double therapy (DT; cyclosporine plus Azathioprine) and group B of 41 patients on CM. RESULTS: After a mean follow-up of 119.8 +/- 32.2 months, we did not observe a significant difference in terms of survival and major events: heart failure, malignancy, dialysis, infections, and CAV. CONCLUSION: We strongly support the use of triple therapy in cardiac transplant recipients because of its known safety and efficacy. However, our experience with CM suggests the utility of this approach.

The Myocardial Performance Index detects chronic cardiac allograft dysfunction sooner than other methods.

AIM: Many noninvasive techniques have been proposed for the early detection of chronic heart graft dysfunction. Diastolic dysfunction may precede systolic dysfunction, and often is prominent; therefore, the aim of the study was to investigate the clinical and prognostic value of a Doppler-derived index of both systolic and diastolic function in heart transplanted patients (Myocardial Performance Index, MPI). METHODS: The MPI was measured in 63 consecutive patients (mean age 55 years, 49 men and 14 women) in sinus rhythm with an orthotopic heart transplantation for at least 1 year (mean 5.3 years) and in 63 age and sex-matched controls. A complete clinical examination was performed at the time of enrollment and was repeated after 3 months. RESULTS: At 3 months, 11 patients (17.5%) presented events (heart failure, hospitalisation or cardiac death). Patients were divided into 2 groups: Group A (52 patients) without events in the follow-up and Group B (11 patients) with events. The values of MPI in Group B (0.55+/-0.19) were significantly higher than values in Group A (0.34+/-0.18, P=0.001). Whereas the values of the index did not differ significantly between Group A and control group (0.34+/-0.18 vs 0.33+/-0.10, P=NS). In the univariate analysis, the population of heart transplanted patients was dichotomised in subgroups by a cut-off MPI of 0.47 and a cut-off ejection fraction (EF) of 50%. Nine patients (41%) with MPI=or>0.47 presented events, while only 2 patients (5%) with MPI<0.47 had any event (P<0.001; c2 12.9). Six patients (85%) with EF<50% had events, while only 5 patients (9%) with EF=or>50% had an event (P<0.001; c2 14). In the multivariate analysis only MPI (chi squared=22.6, P=0.018) and EF (chi squared=20.8, P=0.025) were significant independent predictors of heart failure or cardiac death. By looking at Kaplan-Meyer curves, MPI seems to be better than EF in the earlier detection of graft dysfunction. CONCLUSION: MPI, as a combined systolic and diastolic index, may detect graft dysfunction earlier than EF.

Noninvasive assessment of central circulatory pressures by analysis of ear densitographic changes during the Valsalva maneuver.

The ear densitogram was monitored in 21 consecutive patients with various degrees of myocardial function (New York Heart Association class I to IV) during the standardized Valsalva maneuver to evaluate the quantitative relations between the pattern of response and the central circulatory pressures. The ear densitographic first derivative consistently tracked the aortic pulse pressure during the strain phase of the Valsalva maneuver (beat-to-beat correlation [r] range 0.98 to 0.72). The percent decrease of the densitographic pulse derivative during strain correlated with left ventricular end-diastolic pressure at rest (r = 0.62, p less than 0.001), but not with cardiac output, cardiac index and ejection fraction. Multiple stepwise regression was used to take into account multiple aspects (time intervals and pulse amplitudes) of the pattern of response to the Valsalva maneuver. As a result, both correlations improved substantially (r = 0.97, p less than 0.001 for left ventricular end-diastolic pressure, and r = 0.92, p less than 0.001 for pulmonary artery wedge pressure). In conclusion, the combination of several noninvasive indexes obtained by pulse amplitude and interval changes during the strain phase of the Valsalva maneuver seems to be a new and promising method for noninvasive evaluation of the status of left ventricular filling pressures.

Do hemodynamic responses to the valsalva maneuver reflect myocardial dysfunction?

In 14 consecutive patients with varying myocardial function, evaluation of the Valsalva maneuver was performed using aortic pulse pressure decay to investigate a possible quantitative relationship between the pattern of response and the degree of myocardial dysfunction. The aortic pulse pressure response during strain correlated with resting left ventricular end-diastolic pressure and pulmonary wedge pressure but not with resting cardiac output, cardiac index and ejection fraction. Similar results were obtained when several indices characterizing the aortic pulse pressure decay during Valsalva were used together to predict resting hemodynamic data by multiple regression analysis. In conclusion, quantitative aortic pulse pressure decay during the strain phase of the Valsalva maneuver correlated only moderately with hemodynamic indices used to identify myocardial dysfunction. These results raise doubts about the use of the Valsalva maneuver for the evaluation of myocardial dysfunction.

Treatment of glossopharyngeal neuralgia by carbamazepine.

An elderly woman who presented with Adams-Stokes attacks that were preceded by paroxysms of neuralgia was successfully treated with carbamazepine. Ventricular asystole was provoked by pharyngeal pain and coincided with loss of consciousness. Vagal reflexes are probably responsible for the bradycardia that causes the cardiac symptoms of glossopharyngeal neuralgia. Carbamazepine (600 mg/day) abolished the pharyngeal pain and associated cardiovascular manifestations in this patient for at least ten months.

Electrocardiographic responses to maximal exercise during acute pericarditis and early repolarization.

Exercise testing is contraindicated during active pericarditis because of the possibility of myocarditis. In a patient suspected of having ischemic heart disease, a pericardial rub appeared for the first time following a maximal exercise test, during which the elevated J-points descended to baseline. In two normal volunteer subjects with early repolarization during a maximal exercise test, the elevated J-points behaved similarly. We conclude that, contrary to previous belief, electrocardiographic exercise responses cannot distinguish between pericarditis and early repolarization.