What's Next for Acute Heart Failure Research?

Each year over one million patients with acute heart failure (AHF) present to a United States emergency department (ED). The vast majority are hospitalized for further management. The length of stay and high postdischarge event rate in this cohort have changed little over the past decade. Therapeutic trials have failed to yield substantive improvement in postdischarge outcomes; subsequently, AHF care has changed little in the past 40 years. Prior research studies have been fragmented as either “inpatient” or “ED‐based.” Recognizing the challenges in identification and enrollment of ED patients with AHF, and the lack of robust evidence to guide management, an AHF clinical trials network was developed. This network has demonstrated, through organized collaboration between cardiology and emergency medicine, that many of the hurdles in AHF research can be overcome. The development of a network that supports the collaboration of acute care and HF researchers, combined with the availability of federally funded infrastructure, will facilitate more efficient conduct of both explanatory and pragmatic trials in AHF. Yet many important questions remain, and in this document our group of emergency medicine and cardiology investigators have identified four high‐priority research areas.     

Gray matter differences between pediatric obsessive-compulsive disorder patients and high-risk siblings: A preliminary voxel-based morphometry study

Neuroimaging studies have identified alterations in frontostriatal circuitry in obsessive-compulsive disorder (OCD). Voxel-based morphometry (VBM) allows for the assessment of differences in gray matter density across the whole brain. VBM has not previously been used to examine regional gray matter density in pediatric OCD patients and the siblings of pediatric OCD patients. Volumetric magnetic resonance imaging (MRI) studies were conducted in 10 psychotropic naïve pediatric patients with OCD, 10 unaffected siblings of pediatric patients with OCD, and 10 healthy controls. VBM analysis was conducted using SPM2. Statistical comparisons were performed with the general linear model, implementing small volume random field corrections for a priori regions of interest (anterior cingulate cortex or ACC, striatum and thalamus). VBM analysis revealed significantly lower gray matter density in OCD patients compared to healthy in the left ACC and bilateral medial superior frontal gyrus (SFG). Furthermore, a small volume correction was used to identify a significantly greater gray matter density in the right putamen in OCD patients as compared to unaffected siblings of OCD patients. These findings in patients, siblings, and healthy controls, although preliminary, suggest the presence of gray matter structural differences between affected subjects and healthy controls as well as between affected subjects and individuals at risk for OCD.     

Remission of hormone-refractory prostate cancer attributed to Essiac

Essiac is a popular complementary and alternative medicine (CAM) that is utilized by many cancer patients in North America. Much anecdotal reporting exists about its cancer-fighting qualities, but so far no clinical trials have been preformed to validate those claims. We describe here the case of a 64-year-old man whose hormone-refractory prostate cancer responded well to Essiac tea.     

Noninvasive assessment of coronary vasodilation using magnetic resonance angiography

OBJECTIVES: The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation. BACKGROUND: Coronary vasodilation plays a vital role in the human coronary circulation. Previous studies of epicardial coronary vasodilation have used invasive coronary angiography. Coronary MRA may provide an alternative noninvasive method to directly assess changes in coronary size. METHODS: Thirty-two subjects were studied: 12 patients (age 55 +/- 18 years) and 20 healthy subjects (age 34 +/- 4 years). High-resolution multi-slice spiral coronary MRA (in-plane resolution of 0.52 to 0.75 mm) was performed before and after sublingual nitroglycerin (NTG). Quantitative analysis of coronary vasodilation was performed on cross-sectional images of the right coronary artery (RCA). A time-course analysis of coronary vasodilation was performed in a subset of eight subjects for 30 min after NTG. Signal-to-noise ratio was also measured on the in-plane RCA images. RESULTS: Coronary MRA demonstrated a 23% increase in cross-sectional area after NTG (16.9 +/- 7.8 mm2 to 20.8 +/- 8.9 mm2, p <0.0001), with significant vasodilation between 3 and 15 min after NTG on time-course analysis. The MRA measurements had low interobserver variability (< or =5%) and good correlation with X-ray angiography (r=0.98). The magnitude of vasodilation correlated with baseline cross-sectional area (r=0.52, p=0.03) and age (r=0.40, p=0.019). Post-NTG images also demonstrated a 31% improvement in coronary signal-to-noise ratio (p = 0.002). CONCLUSIONS: Nitroglycerin-enhanced coronary MRA can noninvasively measure coronary artery vasodilation and is a promising noninvasive technique to study coronary vasomotor function.     

Muckle–Wells Cryopyrinopathy: Complex Phenotyping and Response to Therapy in a New Multiplex Kindred

Muckle–Wells syndrome (MWS) is a member of the cryopyrin-associated periodic syndrome family of auto-inflammatory diseases, originally described as a triad of urticaria, sensorineural deafness and amyloidosis. IL-1 blockade is a proven therapy for MWS. The clinical, laboratory and genotypic characteristics of a novel kindred of five individuals with Muckle–Wells syndrome are described. Response to IL-1 blockade therapy in the proband was evaluated. All five affected family members experienced symptoms of multi-organ inflammation. Lead time between symptom onset and diagnosis was approximately 30 years in the proband. Fever was not a universal feature in all affected family members. Anti-IL-1 therapy in the proband resulted in improvements in patient-reported symptoms, inflammatory markers, auditory acuity and reversal of her infertility. Muckle–Wells syndrome is a rare, multisystem, auto-inflammatory syndrome. Delay in diagnosis prevents effective treatment. We propose reversal of infertility to be among the potential benefits of IL-1 inhibition in this disease.     

Cardiac remodelling identified by cardiovascular magnetic resonance in patients with hepatitis C infection and liver disease

Chronic cardiac dysfunction in patients with chronic liver disease (CLD) in the absence of alcohol consumption or other cardiac disease is well described. Whilst functional and morphological features of this condition remain unclear, diastolic dysfunction has been implicated by echocardiography. We aimed to evaluate myocardial structure, function and tissue composition with cardiac magnetic resonance (CMR) imaging in patients with hepatitis C and histological evidence of liver disease on biopsy. Contrast-enhanced CMR imaging for morphological, functional and tissue characterization was performed on 16 patients with CLD and 21 healthy controls. Cardiac structure and function was assessed with standard cine imaging, with Late Gadolinium Enhancement (LGE) and myocardial T1 mapping (pre- and post-contrast) performed to evaluate regional and diffuse myocardial fibrosis respectively. Compared to controls, patients with CLD demonstrated lower left ventricular end-diastolic volume (LVEDV) (138 ± 36 vs. 167 ± 44 mL, p < 0.05), reduced stroke volume (88 ± 20 vs. 109 ± 29 mL, p = 0.016), lower post-contrast myocardial T1 time and higher Partition Coefficient consistent with diffuse myocardial fibrosis (466 ± 78 vs. 545 ± 134 ms and 0.247 ± 0.110 vs. 0.123 ± 0.057 %, p < 0.05 for both). There were no differences in other cardiac parameters including left ventricular mass and ejection fraction (p = NS for all comparisons). No patients in either group had evidence of LGE. Compared to controls, patients with hepatitis C and histological evidence liver involvement have lower LVEDV, SV and increased diffuse myocardial fibrosis, all of which are associated with diastolic dysfunction. LVEF and LV mass were preserved. This may explain in part previous functional observations made by echocardiography.     

Lessons from the 2015 earthquake(s) in Nepal: implication for rehabilitation

Purpose: There has been an increase in the number of natural disasters in recent history, and the rate of disability is increasing among survivors. The most recent major natural disaster was the earthquake(s) that occurred in Nepal on 25 April 2015 and 12 May 2015. In total, more than 8500 people were killed and over 18?500 people were left injured. This article aims to demonstrate the role of rehabilitation professionals in post-disaster relief and beyond in Nepal. Method: This is an experiential account of physiotherapists present during the earthquake and participating in the post-disaster relief. Results: Rehabilitation professionals played an important role in the acute phase post-disaster by providing essential services and equipment. However, discharge planning emerged as an important role for rehabilitation providers in the early days of post-disaster and signaled a relatively new and innovative function that facilitated the heavy imbalance between little supply and tremendous demand for care. In the coming years, rehabilitation will need to support local initiatives that focus on minimizing the long-term effects among people with a newly acquired disability. Conclusions: Rehabilitation serves an important role across the continuum in post-disaster relief from the initial stages to the months and years following an event.

• Implications for Rehabilitation

• Driven by medical advances in acute field medicine, the relative proportion of casualties following natural disasters is decreasing, while relative rates of disability are rising among survivors.

• In post-disaster settings, the growing number of people with newly acquired disabilities will be added to the existing proportion of the population who lived with disabilities, creating a significant growth in the total number of people with disabilities (PWDs) in communities that are often ill prepared to provide necessary services.

• Rehabilitation interventions in the initial stages of emergency humanitarian response can minimize the long-term effects among people with newly acquired disabilities through early activation and prevention of secondary effects.

• Rehabilitation providers thus appear to have an important mediating effect on outcomes of disabilities in the early stages, but must also be strong partners with PWDs to advocate for social and political change in the long term.