Sacubitril-valsartan vs ACE/ARB in pediatric heart failure: A retrospective cohort study.

BACKGROUND: The first angiotensin receptor/neprilysin inhibitor on the market, sacubitril-valsartan, has shown marked improvements in death and hospitalization for heart failure among adults, and is now approved for use in pediatric heart failure. While the ongoing PANORAMA-HF trial is evaluating the effectiveness of sacubitril-valsartan for pediatric patients with a failing systemic left ventricle, the enrollment criteria do not include the majority of pediatric heart failure patients. Additional studies are needed. METHODS: Using the TriNetX database, we performed a propensity score matched, retrospective cohort study to assess the incidence of a composite of all-cause mortality or heart transplant within 1 year. The 519 patients who received sacubitril-valsartan were compared to 519 matched controls who received an angiotensin converting enzyme inhibitor (ACE) or angiotensin II receptor blocker (ARB). RESULTS: There was no significant difference in the incidence of the composite outcome with sacubitril-valsartan over an ACE/ARB (13.3% vs 13.2%, p = 0.95), or among the components of mortality (5.0% vs 5.8%, p = 0.58) or heart transplantation (8.7% vs 7.5%, p = 0.50). Patients who were receiving full goal-directed medical therapy (14.4% vs 16.0%, p = 0.55) also showed no difference in the composite outcome. We observed a significantly increased incidence of hypotension (10% vs 5.2%, p = 0.006) and a trend toward reduced number of hospitalizations per year (mean (SD) 1.3 (4.4) vs 2.0 (9.1), p = 0.09). CONCLUSIONS: Sacubitril-valsartan is not associated with a decrease in the composite of all-cause mortality or heart transplantation within 1 year. Future studies should evaluate the possible reduction in hospitalizations and optimal dosing to minimize hypotension.

Primary Cilia and Their Role in Acquired Heart Disease.

Primary cilia are non-motile plasma membrane extrusions that display a variety of receptors and mechanosensors. Loss of function results in ciliopathies, which have been strongly linked with congenital heart disease, as well as abnormal development and function of most organ systems. Adults with congenital heart disease have high rates of acquired heart failure, and usually die from a cardiac cause. Here we explore primary cilia's role in acquired heart disease. Intraflagellar Transport 88 knockout results in reduced primary cilia, and knockout from cardiac endothelium produces myxomatous degeneration similar to mitral valve prolapse seen in adult humans. Induced primary cilia inactivation by other mechanisms also produces excess myocardial hypertrophy and altered scar architecture after ischemic injury, as well as hypertension due to a lack of vascular endothelial nitric oxide synthase activation and the resultant left ventricular dysfunction. Finally, primary cilia have cell-to-cell transmission capacity which, when blocked, leads to progressive left ventricular hypertrophy and heart failure, though this mechanism has not been fully established. Further research is still needed to understand primary cilia's role in adult cardiac pathology, especially heart failure.

Causes of Shortness of Breath in the Acute Patient: A National Study.

BACKGROUND: Dyspnea is a common and ambiguous complaint that results in 3.4 million emergency department (ED) visits annually. While learners may encounter lists of differential diagnoses to consider while in training, often these lists are not empirically based. We sought to establish an evidence-based differential diagnosis for dyspnea and to determine whether normal vital signs can rule out a life-threatening diagnosis. METHODS: We analyzed data from the National Hospital Ambulatory Medical Care Survey from 2005 to 2014 for ED visits with a chief complaint of dyspnea and tallied the principal discharge diagnosis. We included 10,170 sampled ED visits by adults with a chief complaint of dyspnea, representing nearly 42 million visits nationally. We then calculated the most common principal discharge diagnoses by age group and the frequency of abnormal respiratory vital signs in cases with life-threatening diagnoses. RESULTS: The most represented age group was 45 to 64 years (31.6%). Most visits were discharged directly from the ED (57.5%), while 8.1% required admission to an intensive care unit (ICU). The most common diagnosis in patients aged 18 to 44 was acute asthma exacerbation (14.8%). Obstructive chronic bronchitis was the most common specified diagnosis in both patients ages 45 to 64 (11.1%) and patients ages 65 to 79 (12.4%), while congestive heart failure was the most common for patients ages 80 and over (15.9%). Respiratory vital signs were frequently normal in the 44.6% of visits that resulted in a potentially life-threatening diagnosis but corresponded to increased ICU utilization when abnormal. CONCLUSIONS: For patients with dyspnea, the high utilization of ICUs highlights the importance of an accurate differential. The frequencies established here can be used as pretest probabilities in Bayesian analysis to improve the accuracy of differential diagnosis lists.