Patrick Tansley

BACKGROUND: In patients with severe heart failure, prolonged unloading of the myocardium with the use of a left ventricular assist device has been reported to lead to myocardial recovery in small numbers of patients for varying periods of time. Increasing the frequency and durability of myocardial recovery could reduce or postpone the need for subsequent heart transplantation. METHODS: We enrolled 15 patients with severe heart failure due to nonischemic cardiomyopathy and with no histologic evidence of active myocarditis. All had markedly reduced cardiac output and were receiving inotropes. The patients underwent implantation of left ventricular assist devices and were treated with lisinopril, carvedilol, spironolactone, and losartan to enhance reverse remodeling. Once regression of left ventricular enlargement had been achieved, the beta2-adrenergic-receptor agonist clenbuterol was administered to prevent myocardial atrophy. RESULTS: Eleven of the 15 patients had sufficient myocardial recovery to undergo explantation of the left ventricular assist device a mean (+/-SD) of 320+/-186 days after implantation of the device. One patient died of intractable arrhythmias 24 hours after explantation; another died of carcinoma of the lung 27 months after explantation. The cumulative rate of freedom from recurrent heart failure among the surviving patients was 100% and 88.9% 1 and 4 years after explantation, respectively. The quality of life as assessed by the Minnesota Living with Heart Failure Questionnaire score at 3 years was nearly normal. Fifty-nine months after explantation, the mean left ventricular ejection fraction was 64+/-12%, the mean left ventricular end-diastolic diameter was 59.4+/-12.1 mm, the mean left ventricular end-systolic diameter was 42.5+/-13.2 mm, and the mean maximal oxygen uptake with exercise was 26.3+/-6.0 ml per kilogram of body weight per minute. CONCLUSIONS: In this single-center study, we found that sustained reversal of severe heart failure secondary to nonischemic cardiomyopathy could be achieved in selected patients with the use of a left ventricular assist device and a specific pharmacologic regimen.

BACKGROUND: First described in 1997, breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) was recognised by the World Health Organisation in 2016 as a specific disease. It typically presents as a late seroma-containing atypical, monoclonal T cells which are CD30+ and anaplastic lymphoma kinase negative. Until recently, it was thought that the disease was very rare. However, it is being diagnosed increasingly frequently with 56 cases confirmed in Australia by September 2017 and the estimated incidence revised from 1 in 300,000 to between 1 in 1000 and 1 in 10,000 patients with bilateral implants. There is debate about the spectrum of BIA-ALCL. According to the current WHO classification, BIA-ALCL is a cancer in all cases. Treatment guidelines require that it is treated urgently with a minimum of bilateral removal of implants and capsulectomies. Whilst acknowledging the disease has been under diagnosed in the past, with some notable exceptions the BIA-ALCL literature has given scant attention to the epidemiological evidence. Now that it is known that the disease may occur in up to 1 in 1000 patients with a median of 7.5 years from implantation to diagnosis, understanding it in its epidemiological context is imperative. The epidemiology of cancer and lymphoma in women with breast implants strongly suggests that most patients do not have a cancer that will inevitably progress without treatment but instead a self-limiting lympho-proliferative disorder. Although the possibility of spontaneous regression has been raised and the observation made that treatment delay did not seem to increase the risk of spread, the main objection to the lympho-proliferative hypothesis has been the lack of documented cases of spontaneous regression or resolution. Because all cases currently are considered malignant and treated urgently, only case report evidence, interpreted in the proper epidemiological context, is likely to be available to challenge this thinking. METHODS AND RESULTS: New observations and interpretation of the epidemiology of BIA-ALCL are made. These are supported by the presentation of two cases, which to the best of our knowledge comprise the first documented evidence of spontaneous regression and spontaneous resolution of confirmed BIA-ALCL. CONCLUSIONS: The epidemiology of the disease strongly suggests that the vast majority of cases are not a cancer that will inevitably progress without treatment. The findings presented in the manuscript provide supportive clinical evidence. Consequently, an alternative view of BIA-ALCL with implications for research, diagnosis and clinical management needs to be considered. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .