Intrapericardial treatment of neoplastic pericardial effusions

Pericardial effusion and cardiac tamponade are known complications of many advanced malignancies as lung cancer, breast cancer, lymphomas and leukemias. Initial relief can be easily obtained with percutaneous echo-guided pericardiocentesis, without significant mortality and morbidity and well-tolerated even in critically ill patients. Effusion recurrences can be observed, however, in up to 40% of cases if only simple pericardial drainage is performed. Effective management can be obtained by instillation in the pericardial sac of different agents, with sclerosing or cytostatic activity, like tetracyclines, bleomycin, thiotepa or radionuclides. Intrapericardial sclerotherapy is associated to good results in terms of recurrence prevention and survival improvement. Absence of pericardial effusion at 30 days after drainage can be observed in 70 to 90% of all treated patients, without significant variations among different treatments. No significant side effects are observed, with the exclusion of chest pain during tetracyclines instillation. In our opinion pericardiocentesis associated to intrapericardial sclerotherapy with thiotepa is the best compromise in terms of recurrence prevention, tolerability and costs. Real randomized, case-control studies are moreover required to assess the gold standard of malignant pericardial effusions treatment.     

Intrapericardial bleomycin for the management of cardiac tamponade secondary to malignant pericardial effusion.

A patient with malignant pericardial effusion with cardiac tamponade was treated by the instillation of intrapericardial bleomycin. The tumour deposits elsewhere in the body continued to progress and eventually killed the patient, but drainage and one dose of intrapericardial bleomycin prevented further episodes of pericardial effusion.     

Intrapericardial bleomycin for the management of cardiac tamponade secondary to malignant pericardial effusion.

A patient with malignant pericardial effusion with cardiac tamponade was treated by the instillation of intrapericardial bleomycin. The tumour deposits elsewhere in the body continued to progress and eventually killed the patient, but drainage and one dose of intrapericardial bleomycin prevented further episodes of pericardial effusion.     

Intrapericardial therapeutics: a pharmacodynamic and pharmacokinetic comparison between pericardial and intravenous procainamide delivery

INTRODUCTION: Procainamide delivery into the pericardial space may produce a greater and more prolonged electrophysiologic effect, particularly in thin superficial atrial tissue, compared with intravenous delivery. METHODS AND RESULTS: Swine were randomized to sequential procainamide doses delivered intravenously (n = 6) or into the pericardial space (n = 7). The cumulative pericardial doses were 0.5, 1.5, and 3.5 mg/kg, and the intravenous doses were 2, 10, and 26 mg/kg. Pericardial procainamide prolonged right atrial effective refractory period from baseline by 22% (P < 0.01) but only at the 3.5 mg/kg cumulative dose. This dose slowed interatrial conduction time by 14% (P < 0.05) and raised atrial fibrillation threshold by 70 mA (P < 0.05). Pericardial procainamide had minimal effect on ventricular electrophysiology. Similar results occurred with a single 2 mg/kg pericardial dose in a closed chest model. Intravenous 10 and 26 mg/kg cumulative doses prolonged atrial effective refractory period from baseline by 24% and 18% (P < 0.01), respectively. The 26 mg/kg cumulative intravenous dose slowed interatrial and atrial-ventricular conduction times by 27% and 17%, respectively (P < 0.05), raised atrial fibrillation threshold, and slowed ventricular conduction time by 29% (P < 0.05). Pericardial procainamide produced pericardial fluid concentrations ranging from 250 to 1,500 microg/mL, but plasma concentrations were <1 microg/mL. Intravenous procainamide doses produced pericardial fluid concentrations similar to plasma trough concentrations 0 to 12 microg/mL. CONCLUSION: The single 2 mg/kg and 3.5 mg/kg cumulative pericardial procainamide doses prolonged atrial refractoriness and raised atrial fibrillation threshold similar to the 26 mg/kg cumulative intravenous dose, but the duration of effect was similar between delivery methods. Pericardial procainamide did not affect global or endocardial ventricular electrophysiology nor was it associated with ventricular proarrhythmia.     

Intrapericardial cisplatin for the management of patients with large malignant pericardial effusion

Nine patients (seven men and two women), median age 57 years (range 40–68 years), with large malignant pericardial effusion confirmed by cytological examination, were treated with direct intrapericardial administration of cisplatin. After insertion of a polyurethane catheter, fluid was drained and cisplatin (10 mg in 20 ml normal saline) was instilled over 5 min during 5 consecutive days (total cisplatin dose: 50 mg). If fluid reaccumulation occurred the courses were repeated every 3 weeks. All of the patients achieved a complete therapeutic response (no more fluid reaccumulation). The median time of response was 2.8 months (range 1–24 months). Mild nausea occurred in two patients, supraventricular arrythmia in one patient and infectious complications in one patient. Eight patients died because of disease progression without evidence of cardiac tamponade or stricture. Autopsy, performed in 7 cases, revealed neoplastic involvement of the pericardium in all of the patients, but pericardial effusion was seen in one patient only.     

Treatment of malignant pericardial tamponade with sclerosis induced by instillation of bleomycin

Five patients with pericardial tamponade of neoplastic origin were treated by pericardiocentesis, drainage and local instillation of bleomycin. The pericardial effusion was adequately controlled in all patients. Survival was influenced not by the pericardial involvement, but by the natural evolution of the tumour. Side effects were minimal. The technique of drainage and bleomycin sclerosis is simple, safe, effective and inexpensive for the management of a malignant pericardial tamponade, providing all precautions necessary for diagnosis and pericardiocentesis are adequately taken.     

Severe right-ventricular heart failure due to malignant pericardial mesothelioma

A case of a 63-year old female with symptomatic advanced right-ventricular (RV) heart failure due to malignant pericardial mesothelioma is presented. Echocardiography revealed that RV failure was due to the tumour-induced compression of the right atrium and not due to metastatic mesothelioma involving pericardial sac.     

Heart failure due to a post-traumatic calcified pericardial hematoma

Chest-wall trauma can produce bleeding into the pericardium and initiate a process of inflammation, calcification, and scarring that may eventually produce pericardial constriction. Herein, we present an unusual case of a man who experienced chest trauma at age 16 years, and developed heart failure 40 years later secondary to a large, calcified pericardial hematoma. During its prolonged genesis, the pericardial mass became deeply embedded in the myocardium and produced evidence of both constrictive and restrictive cardiomyopathy. Despite attempted surgical resection, the lesion could not be completely removed, nor could its hemodynamic impact be completely resolved.     

Intrapericardial procedures for cardiac regeneration by stem cells: need for minimal invasive access (AttachLifter) to the normal pericardial cavity

In view of the only modest functional and anatomical improvements achieved by bone marrow-derived cell transplantation in patients with heart disease, the question was addressed whether the intracoronary, transcoronary-venous, and intramyocardial delivery routes are adequate. It is hypothesized that an intrapericardial delivery of stem cells or activators of resident cardiac stem cells increases therapeutic benefits. From such an intrapericardial depot, cells or modulating factors, such as thymosin β4 or Ac-SDKP, are expected to reach the myocardium with sustained kinetics. Novel tools which provide access to the pericardial space even in the absence of pericardial effusion are, therefore, described. When the pericardium becomes attached to the suction head (monitored by an increase in negative pressure), the pericardium is lifted from the epicardium ("AttachLifter"). The opening of the suction head ("Attacher") is narrowed by flexible clamps which grab the tissue and improve the vacuum seal in the case of uneven tissue. A ridge, i.e.,"needle guidance", on the suction head excludes injury to the epicardium, whereby the pericardium is punctured by a needle which resides outside the suction head. A fiberscope can be used to inspect the pericardium prior to puncture. Based on these procedures, the role of the pericardial space and the presence of pericardial effusion in cardiac regeneration can be assessed.     

Intrapericardial treatment of autoreactive pericardial effusion with triamcinolone; the way to avoid side effects of systemic corticosteroid therapy.

AIMS: To evaluate efficacy and safety of intrapericardial treatment with the crystalloid corticosteroid triamcinolone in autoreactive pericardial effusion. METHODS AND RESULTS: Two hundred and sixty consecutive patients with pericarditis/myopericarditis underwent pericardiocentesis, pericardioscopy (Storz-AF1101B1), and epicardial biopsy with pericardial fluid and tissue analyses. By polymerase chain reaction for cardiotropic viruses/bacteria in pericardial effusion and epicardial biopsies as well as by immunohistochemistry and immunocytochemistry of epicardial and endomyocardial biopsies, 84/260 patients were classified as autoreactive pericarditis and underwent intrapericardial instillation of triamcinolone (group 1: 54 patients, 50% males, mean age 48.9 +/- 14.3 years, triamcinolone 600 mg x m(-2) x 24 h(-1); group 2: 30 patients, 46.7% males, mean age 52.5 +/- 12.7 years, triamcinolone 300 mg x m(-2) x 24 h(-1)). Intrapericardial administration of triamcinolone resulted in symptomatic improvement and prevented effusion recurrence in 92.6% vs 86.7% of the patients after 3 months and in 86.0% vs 82.1% after 1 year in groups 1 and 2, respectively (P>0.05). There were no treatment-related acute complications. During the follow-up, 29.6% of the patients developed transitory iatrogenic Cushing syndrome in group 1 in contrast to 13.3% in group 2 (P<0.05).Conclusion Intrapericardial treatment of autoreactive pericarditis with 300 mg x m(-2) x 24 h(-1) of triamcinolone prevented recurrence of symptoms and relapse of effusion as effectively as the 600 mg x m(-2) x 24 h(-1) regimen, but with significantly fewer side effects.     

Experimental efficacy of pericardial instillation of anti-inflammatory agents during percutaneous epicardial catheter ablation to prevent postprocedure pericarditis

Introduction: Pericarditis is a potential complication of catheter-based percutaneous epicardial mapping and ablation. This study evaluates the efficacy and safety of intrapericardial instillation of anti-inflammatory agents after pericardial mapping and ablation in a porcine model of postprocedural pericarditis.
Methods and Results: Twenty-five healthy swine underwent epicardial mapping and ablation after transthoracic subxyphoid puncture. After 60 minutes of continuous catheter manipulation in the pericardial space, radiofrequency energy was delivered in a linear fashion to the epicardial surfaces of both atria. The animals were randomly divided to receive the anti-inflammatory agents, Hyaluronic Acid and Triamcinolone, or control. Fourteen days after ablation, the hearts were excised and the degree of pericardial reaction/adhesions scored. The severity was uniformly graded 4 (intense) in all control animals and was characterized by intense adhesion between the parietal and the visceral pericardium obscuring tissue planes and epicardial anatomy. Hyaluronic Acid provided a mild benefit (score 3.0 ± 0.9), but 2 mg/kg of Triamcinolone significantly attenuated the inflammatory effect (all animals uniformly scored 1.0).
Conclusion: In a porcine model of ablation-related pericarditis, intrapericardial instillation of 2 mg/kg of intermediate-acting corticosteroids effectively prevents post-procedure inflammatory adhesion formation.     

Intrapericardial treatment of autoreactive myocarditis with triamcinolon. Successful administration in patients with minimal pericardial effusion

A major clinical drawback in the treatment of autoreactive pericarditis is its inherent feature to relapse. Intrapericardial treatment with triamcinolone was reported to be efficient in patients with large, symptomatic autoreactive pericardial effusions, avoiding side effects of systemic treatment as well as compliance problems. Intrapericardial treatment with 300 mg/m2 triamcinolone was for the first time performed in patients with autoreactive myopericarditis and minimal pericardial effusions (75 to 110 ml). After 12 months of follow-up both patients are asymptomatic and there were no further recurrences of pericardial effusion. Pericardiocentesis in these patients was performed with the application of the PerDUCER device, guided by pericardioscopy. This device has a hemispherical cavity at the top of the instrument connected with a vacuum-producing syringe. In this cavity the pericardium is captured by vacuum and tangentially punctured by the introducer needle. Pericardium that can be captured, must be up to 2 mm thin to fit into the hemispherical cavity. Pericardioscopy performed from the anterior mediastinum significantly contributed to the success of the procedures enabling visualization of the portions of the pericardium free of adipose tissue or adhesions, suitable for puncture with the PerDUCER. In conclusion, intrapericardial treatment of symptomatic autoreactive myopericarditis with minimal pericardial effusion was safely and efficiently performed in 2 patients. Pericardiocentesis was enabled by means of the PerDUCER device, facilitated by pericardioscopy.     

The failure of granulocytes to produce transcobalamin I TC I.

The hypothesis that transcobalamin I (TC I) originates from granulocytes was tested by comparing the isoelectric focusing (IEF) patterns of the R-type binder (cobalophilin) of vitamin B12 of: 1) lysed granulocytes, 2) 24 h granulocyte output, and 3) plasma. The preparations came from the blood of 5 normal subjects and 4 with myeloproliferative states. The cobalophilin released into a culture of granulocytes resembled the binder in the granulocytes initially. TC I, defined as the alpha1 cobalophilin with components isoelectric between pH 2.9-3.35 and as a carrier of native plasma B12, was not released by granulocytes. The granulocyte binder of leukaemic granulocytes did not differ from the normal in content per cell or amount released.     

Efficacy of percutaneous balloon pericardiotomy and intrapericardial instillation for the management of refractory pericardial effusion: a case report

Percutaneous balloon pericardiotomy and intrapericardial instillation seemed to be less invasive and effective treatments for refractory pericardial effusion. A 65-year-old man who suffered from refractory pericardial effusion associated with gastric cancer and had been hospitalized three times for pericardiocentesis, complained of dyspnea at rest and visited our emergency room. Echocardiography showed a large amount of pericardial effusion all around the heart and signs of cardiac tamponade. Percutaneous balloon pericardiotomy was performed and pericardial effusion turned to pleural effusion. We performed left thoracocentesis. One week later, massive pericardial effusion localized only around the right heart appeared, and pericardiocentesis was performed again. After another month, pericardial effusion around right heart appeared again and intrapericardial instillation with OK-432 (Picibanil) was tried. After the procedure, the pericardial effusion did not increase, and he has had few symptoms for 2 months as an outpatient.