Joel A. Wirth

Pulmonary arteriovenous malformations: diagnosis and transcatheter embolotherapy.

The recent long-term studies from England, France, and the Netherlands, as well as our own, indicate that transcatheter embolotherapy is definitive treatment for PAVM. More recently, Puskas et al have questioned transcatheter embolotherapy as a primary treatment for patients with PAVM (4,56). Their opinion was based on two recurrences among five patients treated with transcatheter embolotherapy. It is not clear why one of the late recurrences in the series by Puskas et al happened, and the other recurrence could have been dut to early deflation of the balloon. Nevertheless, we believe that the collective experience in the larger series reporting on transcatheter embolotherapy of PAVM supports the use of embolotherapy as a primary modality of treatment. Because many patients have bilateral pulmonary malformations and many pulmonary malformations will grow with time, repeated surgical intervention is not ideal therapy. The recurrence rate of 8% reported by Remy et al using coils, and 2% reported by Pollak et al using balloons and coils supports our contention that transcatheter embolotherapy is durable and should be the initial treatment. Also, recurrences are easily retreated by transcatheter embolotherapy with durable results (54). We favor detachable balloons over coils for occluding PAVMs because immediate cross-sectional occlusion of the segmental artery is obtained in a position that preserves the most normal branches. The necessity for repeated introduction of coils, when using the coil method, contributes to longer procedure times with an increased risk of air introduction and, in our experience, a greater risk of postprocedure pleurisy. At the same time, we appreciate that approximately 70% of PAVMs can be occluded equally well with balloons or coils. We also believe that coils have unique advantages over balloons in specific anatomic situations including oversized arteries (where coils are the only option) and for occlusion of the aneurysm of a PAVM. As with all forms of embolotherapy, the interventionalist is best served by having more than one option of treatment, which for PAVM includes both balloons and coils. In summary, PAVMs are effectively managed by means of transcatheter embolotherapy. This therapy has been demonstrated to be safe and durable. Careful technique with modifications depending on the angioarchitecture of the PAVM is required. Patients with PAVMs require follow-up at 1 month and 1 year. While observations documenting serial growth of small PAVMs are somewhat limited, there is published evidence to support their growth with time (35,36). Because of these reports and our unpublished observations, we believe that patients with treated PAVM need long-term follow-up every 5 years to detect growth of small PAVMs that will ultimately reach a size where they may cause paradoxical embolization and stroke (1).

Embolotherapy of large pulmonary arteriovenous malformations: long-term results.

BACKGROUND The purpose of this study was to document the long-term results of transcatheter embolotherapy of large pulmonary arteriovenous malformations (PAVMs). METHODS From a data base of 221 consecutive patients with PAVMs treated by embolotherapy between 1978 and 1995, 45 patients with 52 PAVMs, supplied by feeding arteries 8 mm in diameter or larger, were selected for a retrospective investigation. RESULTS Of 45 patients with 52 large PAVMs, 38 patients (84%) with 44 PAVMs (85%) were cured by the first embolotherapy (mean follow-up, 4.7 years). Acute periprocedural complications included self-limited pleurisy (31%), angina secondary to air embolus (2%), and paradoxical embolization of a device during deployment (4%). None of these events led to short- or long-term sequelae. Seven patients (16%) had persistence of the PAVM attributable to either recanalization (n = 4) or interim accessory artery growth (n = 3). Two of these patients presented with ischemic stroke several years after the initial treatment. Persistent PAVMs (n = 8) were retreated successfully by a second procedure (n = 7), or a third procedure (n = 1) (mean follow-up, 5.9 and 5.3 years, respectively). CONCLUSIONS Embolotherapy of large PAVMs results in permanent occlusion in an overwhelming majority of patients. Continued patency due to recanalization or accessory artery growth is easily detected and treated.

What Is the Role of Oral Prostacyclin Pathway Medications in Pulmonary Arterial Hypertension Management

Purpose of ReviewProstacyclin pathway medications have been shown to be highly efficacious in the treatment of pulmonary arterial hypertension (PAH) through multiple prospective clinical trials and more than two decades of clinical experience. The strongest support for prostacyclin use in PAH management is with parenteral administration. Numerous risks and limitations of parenteral delivery systems as well as significant patient burdens restrict widespread parenteral use. Highly effective and tolerable oral prostacyclin preparations to manage PAH have long been sought. We review the development of the oral prostacyclin agents beraprost, treprostinil, and selexipag and including current indications and limitations. Research into new approaches to the management of PAH, expanding indications for existing agents, and development of novel agents are also discussed.Recent FindingsTwo oral prostacyclin pathway medications, oral treprostinil and selexipag, were FDA approved in December 2013 and 2015, respectively. Current guidelines recommend use of selexipag in WHO-FC II and III (class 1, level B recommendation) and oral treprostinil in WHO-FC III (class 2b, level B recommendation). The use of these medications is challenging due to complexity in dosing and their side effect profiles which limit patient tolerability and acceptance.SummaryThere is a promising role for oral prostacyclin pathway medications in patients with PAH. Future investigations are underway of alternative dose regimens and transitioning from parenteral therapies in order to improve efficacy and tolerability.

Vitamin A Chemoprevention of Lung Cancer

This article describes an ongoing short-term biomarker study of Vitamin A in subjects at high risk for lung cancer. Workers exposed to asbestos and cigarettes have a markedly increased risk of developing lung cancer and parenchymal fibrosis. Epidemiologic and experimental studies have shown that dietary vitamin A has significant anticancer and immunomodulatory effects (1-6). However, whether intervention with supplemental vitamin A can reduce the mortality or morbidity from either disease and the mechanisms involved remains unclear. Airway metaplasia on bronchial biopsy and inflammation on bronchoalveolar lavage (BAL) are considered potential markers for the development of lung cancer and parenchymal fibrosis respectively. Our prior clinical studies (see below) have shown an high incidence of both of these lesions in asbestos-exposed subjects, findings consistent with the idea that the processes of inflammation and carcinogenesis are linked. We have hypothesized that 1) the vitamin A intervention may reduce both bronchial metaplasia and lung inflammation, 2) the mechanism of this effect may be through modulation of relevant pulmonary cytokines, growth factors, and/or oncogenes, and 3) local lung vitamin A status may be a key modifiable host determinant or biomarker of susceptibility. We are performing a double-blind placebo controlled 6 month trial of combination 0-carotene and retinol in 50 subjects at high risk for both lung cancer and parenchymal fibrosis to address these hypotheses. This study should provide valuable data on whether vitamin A can modify potential early markers of lung cancer and fibrosis, the mechanisms involved, and the role of local vitamin A. The findings may lead to effective preventive strategies for lung cancer.