First described in 1983, Barth syndrome (BTHS) is widely regarded as a rare X-linked genetic disease characterised by cardiomyopathy (CM), skeletal myopathy, growth delay, neutropenia and increased urinary excretion of 3-methylglutaconic acid (3-MGCA). Fewer than 200 living males are known worldwide, but evidence is accumulating that the disorder is substantially under-diagnosed. Clinical features include variable combinations of the following wide spectrum: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), endocardial fibroelastosis (EFE), left ventricular non-compaction (LVNC), ventricular arrhythmia, sudden cardiac death, prolonged QTc interval, delayed motor milestones, proximal myopathy, lethargy and fatigue, neutropenia (absent to severe; persistent, intermittent or perfectly cyclical), compensatory monocytosis, recurrent bacterial infection, hypoglycaemia, lactic acidosis, growth and pubertal delay, feeding problems, failure to thrive, episodic diarrhoea, characteristic facies, and X-linked family history. Historically regarded as a cardiac disease, BTHS is now considered a multi-system disorder which may be first seen by many different specialists or generalists. Phenotypic breadth and variability present a major challenge to the diagnostician: some children with BTHS have never been neutropenic, whereas others lack increased 3-MGCA and a minority has occult or absent CM. Furthermore, BTHS was first described in 2010 as an unrecognised cause of fetal death. Disabling mutations or deletions of the tafazzin (TAZ) gene, located at Xq28, cause the disorder by reducing remodeling of cardiolipin, a principal phospholipid of the inner mitochondrial membrane. A definitive biochemical test, based on detecting abnormal ratios of different cardiolipin species, was first described in 2008. Key areas of differential diagnosis include metabolic and viral cardiomyopathies, mitochondrial diseases, and many causes of neutropenia and recurrent male miscarriage and stillbirth. Cardiolipin testing and TAZ sequencing now provide relatively rapid diagnostic testing, both prospectively and retrospectively, from a range of fresh or stored tissues, blood or neonatal bloodspots. TAZ sequencing also allows female carrier detection and antenatal screening. Management of BTHS includes medical therapy of CM, cardiac transplantation (in 14% of patients), antibiotic prophylaxis and granulocyte colony-stimulating factor (G-CSF) therapy. Multidisciplinary teams/clinics are essential for minimising hospital attendances and allowing many more individuals with BTHS to live into adulthood.

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Polydimethylsiloxane (PDMS) is widely used in biomedical science and can form composites that have broad applicability. One promising application where PDMS composites offer several advantages is optical ultrasound generation via the photoacoustic effect. Here, methods to create these PDMS composites are reviewed and classified. It is highlighted how the composites can be applied to a range of substrates, from micrometer‐scale, temperature‐sensitive optical fibers to centimeter‐scale curved and planar surfaces. The resulting composites have enabled all‐optical ultrasound imaging of biological tissues both ex vivo and in vivo, with high spatial resolution and with clinically relevant contrast. In addition, the first 3D all‐optical pulse‐echo ultrasound imaging of ex vivo human tissue, using a PDMS‐multiwalled carbon nanotube composite and a fiber‐optic ultrasound receiver, is presented. Gold nanoparticle‐PDMS and crystal violet‐PDMS composites with prominent absorption at one wavelength range for pulse‐echo ultrasound imaging and transmission at a second wavelength range for photoacoustic imaging are also presented. Using these devices, images of diseased human vascular tissue with both structural and molecular contrast are obtained. With a broader perspective, literature on recent advances in PDMS microfabrication from different fields is highlighted, and methods for incorporating them into new generations of optical ultrasound generators are suggested.

Severe degenerative calcific aortic stenosis (cAS) is common, affecting 3% of individuals aged >75 years and leads to heart failure and death unless the valve is replaced.1,2 Its coexistence with cardiac amyloidosis has been reported, but this has not been studied systematically and the prognostic significance is unknown.3 Cardiac amyloidosis is a progressive infiltrative cardiomyopathy in which deposits of amyloid, almost always of either immunoglobulin light-chain (AL) or transthyretin amyloidosis (ATTR) type, 4-6 accumulate in the ventricular myocardium; ATTR amyloid is usually wildtype (wtATTR) and acquired, but it may also be hereditary and associated with mutant forms of transthyretin. Wild-type cardiac ATTR amyloid has a male preponderance and was formerly known as senile amyloid reflecting its first appearance beyond 60 to 70 years of age and prevalence at autopsy of up to 25% among octogenarians. 7,8 Its natural history and the prevalence of clinically significant ATTR amyloid deposition in the heart are unknown. In a recent small cohort of patients with AS who underwent transcatheter aortic valve Background-Calcific aortic stenosis (cAS) affects 3% of individuals aged >75 years, leading to heart failure and death unless the valve is replaced. Wild-type transthyretin cardiac amyloid is also a disorder of ageing individuals. Prevalence and clinical significance of dual pathology are unknown. This study explored the prevalence of wild-type transthyretin amyloid in cAS by myocardial biopsy, its imaging phenotype and prognostic significance. Methods and Results-A total of 146 patients with severe AS requiring surgical valve replacement underwent cardiovascular magnetic resonance and intraoperative biopsies; 112 had cAS (75±6 years; 57% men). Amyloid was sought histologically using Congo red staining and then typed using immunohistochemistry and mass spectrometry; patients with amyloid underwent clinical evaluation including genotyping and 99m TC-3,3-diphosphono-1,2-propanodicarboxylic-acid (DPD) bone scintigraphy. Amyloid was identified in 6 of 146 patients, all with cAS and >65 years (prevalence 5.6% in cAS >65). All 6 patients had wild-type transthyretin amyloid (mean age 75 years; range, 69-85; 4 men), not suspected on echocardiography. Cardiovascular magnetic resonance findings were of definite cardiac amyloidosis in 2, but could be explained solely by AS in the other 4. Postoperative DPD scans demonstrated cardiac localization in all 4 patients who had this investigation (2 died prior). At follow-up (median, 2.3 years), 50% with amyloid had died (versus 7.5% in cAS; 6.9% in age >65 years). In univariable analyses, the presence of transthyretin amyloidosis amyloid had the highest hazard ratio for death (9.5 [95% confidence interval, 2.5-35.8]; P=0.001). Conclusions-Occult wild-type transthyretin cardiac amyloid had a prevalence of 6% among patients with AS aged >65 years undergoing surgical aortic valve replacement and was associated with a poor outcome. (Circ Cardiovasc Imaging. 2016;9:e005066.