Lower Platelet Count Following Rabbit Antithymocyte Globulin Induction Is Associated With Less Acute Cellular Rejection in Heart Transplant Recipients.

BACKGROUND: Unlike lymphodepletion, a decrease in platelet count following induction immunosuppressive therapy with polyclonal rabbit antithymocyte globulin (rATG) is deemed as an adverse event. However, this phenomenon may represent a particular rATG antirejection mechanism. METHODS: This retrospective single-center study included 156 patients who received a heart transplant (HTx) between 2010 and 2018. All patients received rATG induction therapy for 5 days. Absolute lymphocyte count (ALC) and platelet counts were assessed on days 0, 7, and 14 following HTx. The primary outcome of the study was the first occurrence of acute cellular rejection (ACR) defined as grade ≥ 1B within 24 months after HTx. RESULTS: Both ALC and platelet counts decreased rapidly after induction. During the 24-month follow-up period, 17% of patients had ACR. Patients with ACR had significantly higher platelet count on day 7 (145 vs 104, P < .001) and higher ALC on day 14 (162 vs 130, P = .035) than those without rejection. Patients in the highest platelet count quartile showed more ACR (50% in quartile 4 vs 0% in quartile 1, P = .006) as well as a higher cumulative total rejection score. Univariate analysis showed that ACR was associated with platelet count on day 7, recipient age, and pretransplant cytomegalovirus IgG serology. In multivariable regression analysis, platelet count on day 7 was the most accurate predictor of ACR. CONCLUSIONS: Lower platelet count after induction with rATG is associated with less ACR. This suggests platelet involvement in antirejection mechanisms of rATG and a possible rationale for targeting platelets in future immunosuppressive strategies.

A pragmatic approach to the use of inotropes for the management of acute and advanced heart failure: An expert panel consensus.

Inotropes aim at increasing cardiac output by enhancing cardiac contractility. They constitute the third pharmacological pillar in the treatment of patients with decompensated heart failure, the other two being diuretics and vasodilators. Three classes of parenterally administered inotropes are currently indicated for decompensated heart failure, (i) the beta adrenergic agonists, including dopamine and dobutamine and also the catecholamines epinephrine and norepinephrine, (ii) the phosphodiesterase III inhibitor milrinone and (iii) the calcium sensitizer levosimendan. These three families of drugs share some pharmacologic traits, but differ profoundly in many of their pleiotropic effects. Identifying the patients in need of inotropic support and selecting the proper inotrope in each case remain challenging. The present consensus, derived by a panel meeting of experts from 21 countries, aims at addressing this very issue in the setting of both acute and advanced heart failure.

Manual Intracardiac Electrogram Method Is Accurate Alternative to Echocardiography for Atrioventricular and Interventricular Optimization in Cardiac Resynchronization Therapy.

Some manufacturers do not provide automated intracardiac electrogram method (IEGM) systems for atrioventricular (AV) and interventricular (VV) delay optimization in cardiac resynchronization therapy (CRT). We aimed to evaluate the accuracy of manual IEGM method in 48 patients previously implanted with Medtronic Syncra CRT. All patients underwent standard device interrogation followed by CRT optimization by IEGM method and by echocardiography one month after implantation. The patient mean age was 60.7±11.8 years and there were 33 (68.8%) males. After CRT implantation, the left ventricular ejection fraction increased from 28.0±7.9% to 39.1±11.0% (p<0.001). Optimal aortic flow Velocity Time Integral (aVTI) was obtained when VV was set to 20-50 ms left ventricular pre-activation. There was a strong correlation between VV values determined by echocardiography and IEGM (R=0.823, p<0.001). We found no significant difference in AV, VV and aVTI values between echocardiography and IEGM method. However, IEGM was significantly less time-consuming than echocardiography [20 (10-28) vs. 40 (35-60) minutes, p<0.001]. Manual IEGM method may be good alternative to echocardiography and automated IEGM method. It also emphasizes the need for implementation of automated IEGM systems in as many CRT devices as possible.

Urgent Heart Retransplant in an Adult Patient With Anthracycline-Induced Cardiomyopathy After Diffuse Large B-Cell Lymphoma - Case Report.

Heart retransplant is a treatment option for some patients with graft failure. With heart donor short-age, it is important to assess candidates carefully for cardiac retransplant. An adult patient had a successful urgent heart retransplant due to severe toxic cardiomyopathy (anthracycline-induced) after posttransplant lymphoproliferative disease that was a diffuse large B-cell lymphoma.

Pretransplant and perioperative predictors of early heart transplantation outcomes.

Aim. To identify predictors of 3-month mortality after heart transplantation in a Croatian academic center. Methods. A retrospective review of institutional database identified 117 heart transplantations from January 2008 to July 2014. Two children <14 years were excluded from the study. The remaining 115 patients were dichotomized into survivors and non-survivors adjudicated at 3-months postoperatively, and their demographic, clinical, and longitudinal hemodynamic data were analyzed. Results. 3-month survival after heart transplantation was 86%. Non-survivors were older (59±8 vs 50±14 years, P=0.009), more likely to have previous cardiac surgery (44% vs 19%; odds ratio [OR] 3.28, 95% confidence interval [CI] 1.08-9.90; P=0.029), lower body mass index (BMI) (25±4 vs 28±2 kg/m(2), P=0.001), and be diabetics (44% vs 23%; OR 2.57, 95% CI 0.86-7.66; P=0.083). Creatinine clearance was marginally superior among survivors (59=19 vs 48 ± 20 mL/min, P=0.059). Donor age and sex did not affect outcomes. Non-survivors were more likely to have had ischemic cardiomyopathy (69% vs 32%, P=0.010). Postoperative utilization of epinephrine as a second line inotropic agent was a strong predictor of mortality (63% vs 7%; OR 21.91; 95% CI 6.15-78.06; P<0.001). Serum lactate concentrations were consistently higher among non-survivors, with the difference being most pronounced 2 hours after cardiopulmonary bypass (9.8±3.5 vs 5.2±3.2 mmol/L, P<0.001). The donor hearts exhibited inferior early hemodynamics in non-survivors (cardiac index 3.0±1.0 vs 4.0±1.1 L/min/m(2), P=0.001), stroke volume (49±24 vs 59±19 mL, P=0.063), and left and right ventricular stroke work indices (18±8 vs 30±11 g/beat/m(2), P<0.001 and 5±3 vs 7±4 g/beat/m(2), P=0.060, respectively). Non-survivors were more likely to require postoperative re-sternotomy (50% vs 12%; OR 7.25, 95% CI 2.29-22.92; P<0.001), renal replacement therapy (RRT) (69% vs 9%; OR 22.00, 95% CI 6.24-77.54; P<0.001), and mechanical circulatory assistance (MCS) (44% vs 5%; OR 14.62, 95% CI 3.84-55.62; P<0.001). Binary logistic regression revealed recipient age (P=0.024), serum lactates 2 hours after CPB (P=0.007), and epinephrine use on postoperative day 1 (P=0.007) to be independently associated with 3-month mortality. Conclusion. Pretransplant predictors of adverse outcome after heart transplantation were recipient age, lower BMI, ischemic cardiomyopathy, reoperation and diabetes. Postoperative predictors of mortality were inferior donor heart hemodynamics, epinephrine use, and serum lactate concentrations. Non-survivors were more likely to require re-sternotomy, MCS, and RRT.

Cardiac allograft vasculopathy: diagnosis, therapy, and prognosis.

Development of cardiac allograft vasculopathy represents the major determinant of long-term survival in patients after heart transplantation. Due to graft denervation, these patients seldom present with classic symptoms of angina pectoris, and the first clinical presentations are progressive heart failure or sudden cardiac death. Although coronary angiography remains the routine technique for coronary artery disease detection, it is not sensitive enough for screening purposes. This is especially the case in the first year after transplantation when diffuse and concentric vascular changes can be easily detected only by intravascular ultrasound. The treatment of the established vasculopathy is disappointing, so the primary effort should be directed toward early prevention and diagnosis. Due to diffuse vascular changes, revascularization procedures are restricted only to a relatively small proportion of patients with favorable coronary anatomy. Percutaneous coronary intervention is preferred over surgical revascularization since it leads to better acute results and patient survival. Although there is no proven long-term advantage of drug-eluting stents for the treatment of in-stent restenosis, they are preferred over bare-metal stents. Severe vasculopathy has a poor prognosis and the only definitive treatment is retransplantation. This article reviews the present knowledge on the pathogenesis, diagnosis, treatment, and prognosis of cardiac allograft vasculopathy.