Mordechai R. Kramer

Sudden unexpected death in persons <40 years of age

Abstract This study retrospectively assesses the underlying causes of sudden unexpected death and the occurrence of prodromal symptoms in 162 subjects (aged 9 to 39 years) over a 10-year period (1976 to 1985). Underlying cardiac diseases accounted for sudden death in 73% and noncardiac causes in 15% of subjects. In 12% of subjects, the causes were unidentifiable. Myocarditis (22%), hypertrophic cardiomyopathy (22%) and conduction system abnormalities (13%) were the major causes in 32 subjects aged

Macitentan for the treatment of idiopathic pulmonary fibrosis: the randomised controlled MUSIC trial

Idiopathic pulmonary fibrosis is a progressive, fatal disease. This prospective, randomised, double-blind, multicentre, parallel-group, placebo-controlled phase II trial (NCT00903331) investigated the efficacy and safety of the endothelin receptor antagonist macitentan in idiopathic pulmonary fibrosis. Eligible subjects were adults with idiopathic pulmonary fibrosis of <3 years duration and a histological pattern of usual interstitial pneumonia on surgical lung biopsy. The primary objective was to demonstrate that macitentan (10 mg once daily) positively affected forced vital capacity versus placebo. Using a centralised system, 178 subjects were randomised (2:1) to macitentan (n=119) or placebo (n=59). The median change from baseline up to month 12 in forced vital capacity was -0.20 L in the macitentan arm and -0.20 L in the placebo arm. Overall, no differences between treatments were observed in pulmonary function tests or time to disease worsening or death. Median exposures to macitentan and placebo were 14.5 months and 15.0 months, respectively. Alanine and/or aspartate aminotransferase elevations over three times upper limit of normal arose in 3.4% of macitentan-treated subjects and 5.1% of placebo recipients. In conclusion, the primary objective was not met. Long-term exposure to macitentan was well tolerated with a similar, low incidence of elevated hepatic aminotransferases in each treatment group. Long-term exposure to macitentan was well tolerated in IPF in a trial that did not meet its primary end-point http://ow.ly/p0RDL

Cyclosporine and Itraconazole Interaction in Heart and Lung Transplant Recipients

Excerpt Itraconazole is a new triazole antifungal (1-3). The infrequency of serious toxicity makes it particularly appropriate in patients receiving cyclosporine therapy, in whom nephrotoxicity is ...

Recovery of the right ventricle after single-lung transplantation in pulmonary hypertension

Single-lung transplantation has been successfully performed in patients with pulmonary fibrosis and emphysema. In contrast, patients with end-stage pulmonary hypertension (either primary or secondary to Eisenmengers syndrome) have conventionally been offered heart-lung transplantation. The rationale underlying this approach is that chronic pulmonary hypertension results in irreversible right ventricular dilatation and failure. Recovery of the right ventricle has previously been reported after thromboendarterectomy for chronic large-vessel pulmonary embolism, correction of atrial septal defect or mitral valve replacement. The evolution of right ventricular morphology and function after lung transplantation has not been previously described. This study examines the reversibility of right ventricle dysfunction following normalization of pulmonary artery pressure after single-lung transplantation in 4 patients with pulmonary hypertension. Cardiac function was assessed using electrocardiography, echocardiography and radionuclide angiography. Pulmonary hemodynamic measurements, including pulmonary artery pressure and pulmonary vascular resistance, decreased in all patients after single-lung transplantation. Electrocardiographic changes observed were leftward shift in the QRS axis, and a decrease in P-wave amplitude and in right ventricular force. Echocardiographic examination revealed decreased right atrial, right ventricular and tricuspid valve annular dimensions, normalization of septal motion, and decreased tricuspid regurgitation. Thus, improved pulmonary hemodynamics after single-lung transplantation for pulmonary vascular disease results in reversal of right heart dilatation and dysfunction, and improved myocardial performance. The extent of right ventricular dysfunction beyond which recovery is unlikely to occur has yet to be determined.

Lung transplantation in patients with scleroderma: case series, review of the literature, and criteria for transplantation

Abstract:  Backgrounds:  The use of lung transplantation (LTX) to treat respiratory failure because of scleroderma is controversial. We present our experience, review the current literature, and suggest specific criteria for LTX in scleroderma. Of the 174 patients who underwent LTX at our center, seven (4%) had scleroderma‐associated respiratory failure.

Histological diagnosis of interstitial lung diseases by cryo-transbronchial biopsy.

The gold standard for the histological diagnosis of interstitial lung diseases (ILD) is an open lung biopsy (OLB). Tissue samples obtained by forceps transbronchial lung biopsies (TBB) are usually too small. We aim to evaluate the efficacy and safety of cryo‐TBB for the diagnosis of ILD and to explore its role as substitute for OLB.

Trimethoprim-sulfamethoxazole prophylaxis for Pneumocystis carinii infections in heart-lung and lung transplantation--how effective and for how long?

Pneumocystis carinii pneumonia (PCP) is a common clinical problem in the setting of organ transplantation, particularly in heart-lung and lung allograft recipients. Without prophylactic measurements, the incidence of P carinii pneumonia can reach up to 88% of heart-lung transplant recipients. We conducted a retrospective analysis of the Stanford heart-lung and lung transplant experience in order to assess the efficacy of the prophylactic therapy and to try to define the duration of therapy necessary for prevention. During a 9-year period 82 heart-lung and 13 single-lung transplants were performed. Of the patients not on prophylaxis therapy 27% (13 patients) developed P carinii infection as compared with 0% of patients on trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis. The incidence of PCP infection peaked between 3 and 6 months posttransplantation. No case of infection was observed before the 7th week posttransplant. PCP was more common following induction immunosuppression with OKT3 as compared with RATG (P less than 0.05). All cases of infections later than one year posttransplant were associated with recent increase in the immunosuppression regimen with high-dose corticosteroids for treatment of acute or chronic (obliterative bronchiolitis) rejection. Although our study is retrospective and based on various immunosuppressive and diagnostic technique periods, it seems that TMP-SMX is highly effective in preventing PCP infections in heart-lung and lung transplant recipients. Twelve months of therapy is probably a sufficient length of therapy if immunosuppressive therapy is stable. However, whenever augmentation in the immunosuppression regimen is indicated, prophylactic therapy should promptly be restarted.

Pulmonary function in patients with Diabetes mellitus

Background: Pulmonary complications of diabetes mellitus have been poorly characterized. Although some authors have reported normal pulmonary function, others found abnormalities in lung volumes, pulmonary mechanics, and diffusing capacity. Subjects and Methods: We studied pulmonary function in a group of patients with diabetes using a combined cardiopulmonary exercise test. Twenty‐seven patients with diabetes aged 48±13 years participated in the study. Results: Overall, forced vital capacity, forced expiratory volume in 1 second, and forced expiratory flow, midexpiratory phase, were within the predicted values, but the residual volume/total lung capacity ratio was slightly elevated. Comparison by diabetes type showed nonsignificant differences in forced expiratory volume in 1 second and forced expiratory flow, midexpiratory phase. Residual volume/total lung capacity ratio was significantly elevated in type 1 patients compared with type 2. Carbon monoxide diffusion capacity (Dlco) was normal in both groups. There was no correlation between the results on pulmonary function test and duration of disease, presence of microangiopathy, or glycemic control. The Dlco was significantly lower in patients with microangiopathic changes, but not when Dlco was corrected for alveolar volume. On the cardiopulmonary exercise test, maximal workload, maximum oxygen uptake, and maximal heart rate were less than predicted, whereas anaerobic threshold and ventilatory reserve were normal. No significant differences were noted in diabetes type, and there was no correlation between parameters of cardiopulmonary exercise test and the other variables. Conclusion: Spirometric values are preserved in patients with diabetes mellitus, and there are no defects in diffusing capacity. Cardiovascular factors may account for impaired physical performance. There is no need for routine screening of pulmonary function among diabetic patients.

Peripheral Arterial Stiffness and Endothelial Dysfunction in Idiopathic and Scleroderma Associated Pulmonary Arterial Hypertension

Objective. Pulmonary endothelial dysfunction and increased reflection of pulmonary pressure waves have been reported in pulmonary arterial hypertension (PAH). However, the systemic vascular involvement is not fully understood. Our study focused on the systemic arterial stiffness and endothelial involvement in idiopathic and scleroderma associated PAH. Methods. Peripheral arterial stiffness and endothelial function were evaluated in 38 patients with idiopathic (n = 28) and scleroderma associated (n = 10) PAH, and 21 control subjects (13 healthy; 8 with scleroderma and normal pulmonary pressure). All participants underwent clinical and cardiopulmonary evaluation. Arterial stiffness was measured through the fingertip tonometry derived augmentation index (AI), which is the boost increase in the late systolic pressure wave after the initial systolic shoulder. Endothelial function was measured by forearm blood flow dilatation response to brachial artery occlusion by a noninvasive plethysmograph (EndoPAT 2000), which is associated with nitric oxide-dependent vasodilatation and yields a peripheral arterial tone (PAT) ratio. Results. Mean systolic pulmonary pressure was 70.5 ± 21.6 mm Hg (idiopathic-PAH) and 69.3 ± 20 mm Hg (scleroderma-PAH). AI was higher in scleroderma patients (10.5% ± 19.6% in healthy controls, 9.0% ± 21.5% in idiopathic-PAH, 20.1% ± 19.1% in scleroderma-PAH, and 24.4% ± 18.9% in scleroderma-controls; nonsignificant). PAT ratio was significantly lower (p < 0.05) than control values in idiopathic-PAH and scleroderma-PAH (PAT ratio: control 2.20 ± 0.25; idiopathic 1.84 ± 0.51; scleroderma 1.66 ± 0.66). AI was not correlated to endothelial dysfunction. There were no differences between the 2 PAH patient groups in age, body mass index, New York Heart Association classification, or 6-min walk test. Conclusion. Our study shows a trend towards increased arterial stiffness in scleroderma (nonsignificant), and also peripheral endothelial dysfunction in idiopathic-PAH and in scleroderma-PAH. These findings suggest involvement of different vessels in scleroderma-PAH compared to idiopathic-PAH.

Exercise Training-Based Pulmonary Rehabilitation Program Is Clinically Beneficial for Idiopathic Pulmonary Fibrosis

Background: Idiopathic pulmonary fibrosis (IPF) is a chronic, devastating, interstitial lung disease, with few therapeutic options. IPF is characterized by pulmonary restriction, dyspnea, hypoxemia, exercise intolerance and poor quality of life (QOL). Objectives: We aimed to examine the effect of exercise training (ET) on clinical outcomes in IPF patients. Methods: A randomized controlled study included thirty-two IPF patients (aged 68 ± 8 years) who were allocated either to the ET group (n = 15), participating in a 12-week, twice-weekly 60-min supervised ET-based pulmonary rehabilitation program, or to a control group (n = 17) continuing with regular medical treatment alone. Cardiopulmonary exercise test, 6-min walking distance (6MWD) test, 30-second chair-stand test, pulmonary function tests, dyspnea and QOL were assessed at baseline and at the end of the 12-week intervention. Results: Significant differences were observed between the ET and the control groups in raw mean deltas (Δ = post- - pre-intervention): Δ6MWD, 81 m, p < 0.001; ΔVO2 peak, 2.6 ml/kg/min, p = 0.002; Δwork rate, 22 W, p < 0.001; Δanaerobic threshold, 3.1 ml/kg/min, p < 0.001, and ΔFVC % predicted, 6%, p = 0.038. Dyspnea, QOL and 30-second chair-stand were also improved significantly following the program. Conclusions: ET improves exercise tolerance, functional capacity, pulmonary function, dyspnea and QOL in patients with IPF, suggesting a short-term treatment efficacy for clinical improvement, and should be considered the standard care for IPF.