Pulmonary vascular remodeling in pulmonary hypertension due to chronic heart failure.

UNLABELLED: Pulmonary hypertension (PHT) associated with chronic heart failure (CHF) is a risk factor of right ventricular failure after heart transplantation (HT). Our aim was to study pulmonary vascular changes in patients with CHF and to assess any correlation with haemodynamic data. METHODS: We studied 17 HT recipients with preoperative CHF who died shortly after HT. Preoperative haemodynamic information was obtained immediately before HT. Vascular lesions in muscular arteries were assessed by linear morphometry. Haemodynamic data were correlated with the morphologic changes. RESULTS: Mean transpulmonary gradient (TPG) was 8.9+/-4.5 mm Hg and pulmonary vascular resistance (PVR) was 2.25+/-1.34 Wu. According to the threshold for at-risk PHT (TPG>12 mm Hg or PVR>2.5 Wu), six patients had at-risk PHT. Medial thickness was 23.82+/-7.23% in patients with at-risk PHT and 17.16+/-3.24% in patients without at-risk PHT (p=0.018). CONCLUSIONS: Medial hypertrophy of muscular pulmonary arteries is more common and severe than expected in patients with CHF, even in patients without at-risk PHT. This structural change could explain why PHT, even in range of values not excluding HT, is a risk factor for right ventricular failure after HT and influences post-HT haemodynamic behaviour.

A framework for clinical reasoning in adult cardiology.

It is well known that an expert clinician formulates a diagnostic hypothesis with little clinical data. In comparison, students have difficulties in doing so. The mental mechanism of diagnostic reasoning is almost unconscious and therefore difficult to teach. The purpose of this essay (devoted to 2nd-year medical students) is to present an integrating framework to teach clinical reasoning in cardiology. By analyzing cardiology with a synthetic mind, it becomes apparent that although there are many diseases, the heart, as an organ, reacts to illness with only six basic responses. The clinical manifestations of heart diseases are the direct consequence of these cardiac responses. Considering the six cardiac responses framework, diagnostic reasoning is done in three overlapping steps. With the presented framework, the process of reasoning becomes more visual and needs less clinical data, resembling that of the expert clinician.

Induction treatment with monoclonal antibodies for heart transplantation.

Individualization of induction therapy for heart transplantation (HT) is needed, given that only patients at significant risk for fatal rejection seem to present a favorable risk-benefit ratio. The question whether monoclonal interleukin 2 antagonists or antilymphocyte antibodies should be recommended remains unanswered. As most studies suggest that they have similar efficacy in preventing acute rejection, other variables related to safety or management costs should be taken into account. The cytokine release syndrome, associated with the use of OKT3, complicates management of HT patient. The experience in our center with 2 consecutive cohorts, treated with basiliximab (BAS) and OKT3, respectively, suggests that the use of BAS is associated, in addition to similar immunosuppressive efficacy and better safety profile than OKT3, with simpler patient management during the initial hospital stay, which could be associated with a reduction in posttransplant costs. Because few centers continue to use OKT3 as induction therapy in HT, more studies comparing cost-effectiveness of BAS vs polyclonal antilymphocyte antibodies (ATG) are needed.

Acute rejection after heart transplantation.

Acute rejection (AR) seems to be less common with current immunosuppressive strategies; however, it remains a major cause of morbidity and mortality in the first year following heart transplantation. Despite great interest in noninvasive methods for detecting rejection, the endomyocardial biopsy remains the standard method for AR identification and, recently, the cardiac biopsy grading system has been reviewed. Moreover, the availability of several immunosuppressive drug combinations has generated confusion in the minds of clinicians. This review will focus on recently published studies that are related to the clinical impact of AR, combination regimens of chronic maintenance immunosuppression and specific therapeutic options for treating AR.

Sirolimus-associated interstitial pneumonitis in 3 heart transplant recipients.

Sirolimus-induced interstitial pneumonitis (SIP) has been reported mainly in renal transplant recipients. However, it has recently been reported with increasing frequency in heart transplantation (HT) patients switched from calcineurin inhibitors (CNIs) to sirolimus. We reviewed the medical records of 30 patients who were treated with sirolimus. Twenty-seven patients were switched from a CNI, 2 patients were initially treated with sirolimus and in 1 patient sirolimus was used to treat a persistent cellular acute rejection. Three patients developed SIP. Symptoms included dry cough, shortness of breath and hypoxemia. High-resolution computed tomography (HRCT) scans showed patchy pulmonary consolidation in a peribronchial distribution or diffuse interstitial pulmonary infiltrates. Before onset of SIP, 2 patients had previous heart failure. Sirolimus discontinuation resulted in a complete resolution of symptoms. SIP is a common and severe adverse event (10%) in HT recipients treated with sirolimus. Drug discontinuation can dramatically improve clinical status. Previous lung injury may play a role in SIP pathogenesis.

Impact of diltiazem administration and cyclosporine levels on the incidence of acute rejection in heart transplant patients.

To identify the clinical factors associated with acute rejection (AR) in the first year after heart transplantation (HT), we analysed 112 patients. All patients received OKT3 and standard triple-drug therapy. We analysed the following variables to determine their relationship with AR: age and gender, panel-reactive antibodies, HLA-DR mismatch, use of Sandimmune vs Neoral, diltiazem administration, and cyclosporine levels in week 2 and months 1, 2, and 3 after HT. Fifty-two patients had no AR and 49 had at least one episode. The variables independently associated with absence of AR were diltiazem administration (odds ratio 0.306, confidence limit 0.102-0.921) and cyclosporine level in the first month after HT (odds ratio 0.996, confidence limit 0.992-0.999). Furthermore, a cyclosporine level greater than 362 ng/ml in the first month predicted the absence of AR. In conclusion, a cyclosporine level greater than 362 ng/ml and diltiazem administration in the first month after HT reduce AR during the first year. Both cyclosporine level and diltiazem show a large and independent protective effect.