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Aims: Tafamidis improves clinical outcomes in transthyretin amyloid cardiomyopathy (ATTR‐CM), yet how tafamidis affects cardiac structure and function remains poorly described. This study prospectively analysed the effect of tafamidis on 12‐month longitudinal changes in cardiac structure and function by cardiac magnetic resonance (CMR) compared with the natural course of disease in an untreated historic control cohort. Methods and results: ATTR‐CM patients underwent CMR at tafamidis initiation and at 12 months. Untreated patients with serial CMRs served as reference to compare biventricular function, global longitudinal strain (GLS), LV mass and extracellular volume fraction (ECV). Thirty‐six tafamidis‐treated (n = 35; 97.1% male) and 15 untreated patients (n = 14; 93.3% male) with a mean age of 78.3 ± 6.5 and 76.9 ± 6.5, respectively, and comparable baseline characteristics were included. Tafamidis was associated with preserving biventricular function (LVEF (%): 50.5 ± 12 to 50.7 ± 11.5, P = 0.87; RVEF (%): 48.2 ± 10.4 to 48.2 ± 9.4, P = 0.99) and LV‐GLS (−9.6 ± 3.2 to −9.9 ± 2.4%; P = 0.595) at 12 months, while a significantly reduced RV‐function (50.8 ± 7.3 to 44.2 ± 11.6%, P = 0.028; P (change over time between groups) = 0.032) and numerically worsening LVGLS (−10.9 ± 3.3 to −9.1 ± 2.9%, P = 0.097; P (change over time between groups) = 0.048) was observed without treatment. LV mass significantly declined with tafamidis (184.7 ± 47.7 to 176.5 ± 44.3 g; P = 0.011), yet remained unchanged in untreated patients (163.8 ± 47.5 to 171.2 ± 39.7 g P = 0.356, P (change over time between groups) = 0.027). Irrespective of tafamidis, ECV and native T1‐mapping did not change significantly from baseline to 12‐month follow‐up (P > 0.05). Conclusions: Compared with untreated ATTR‐CM patients, initiation of tafamidis preserved CMR‐measured biventricular function and reduced LV mass at 12 months. ECV and native T1‐mapping did not change significantly comparable to baseline in both groups. [ABSTRACT FROM AUTHOR]

This document summarizes a study that examined the effects of tafamidis therapy on the heart structure and function of patients with transthyretin amyloid cardiomyopathy (ATTR-CM). The study found that tafamidis treatment resulted in a decrease in left ventricular mass after 12 months, but did not significantly impact other cardiac parameters or global strain. The findings provide valuable information on the long-term effects of tafamidis therapy on cardiac remodeling and function in patients with ATTR-CM. However, the study had limitations, such as a small sample size and lack of randomization, and further research is needed to establish reliable markers for monitoring and evaluating treatment efficacy. [Extracted from the article]

High-dose dobutamine magnetic resonance stress testing has been shown to be superior to dobutamine stress echocardiography for diagnosis of coronary artery disease (CAD). We determined the feasibility of quantitative myocardial tagging during low- and high-dose dobutamine stress and tested the ability of global systolic and diastolic quantitative parameters to identify patients with significant CAD. Twenty-five patients suspected of having significant CAD were examined with a standard high-dose dobutamine/atropine stress magnetic resonance protocol (1.5-T scanner, Philips). All patients underwent invasive coronary angiography as the standard of reference for the presence (n = 13) or absence (n = 12) of significant CAD. During low-dose dobutamine stress, systolic (circumferential shortening, systolic rotation, and systolic rotation velocity) and diastolic (velocity of circumferential lengthening and diastolic rotation velocity) parameters changed significantly in patients without CAD (all P < 0.05 vs. rest) but not in patients with CAD. Identification of patients without and with CAD during low-dose stress was possible using the diastolic parameter of 'time to peak untwist.' At high-dose stress, none of the global systolic or diastolic parameters showed the potential to identify the presence of significant CAD. With myocardial tagging, a quantitative analysis of systolic and diastolic function was feasible during low- and high-dose dobutamine stress. In our study, the diastolic parameter of time to peak untwist as assessed during low-dose dobutamine stress was the most promising global parameter for identification of patients with significant CAD. Thus quantitative myocardial tagging may become a tool that reduces the need for high-dose dobutamine stress. dobutamine; echocardiography; systolic rotation velocity; time to peak untwist; diastolic rotation velocity

Abstract Background Poly(3-hydroxybutyrate) (PHB) granules are important storage compounds of carbon and energy in many prokaryotes which allow survival of the cells in the absence of suitable carbon sources. Formation and subcellular localization of PHB granules was previously assumed to occur randomly in the cytoplasm of PHB accumulating bacteria. However, contradictionary results on subcellular localization of PHB granules in Ralstonia eutropha were published, recently. Results Here, we provide evidence by transmission electron microscopy that PHB granules are localized in close contact to the nucleoid region in R. eutropha during growth on nutrient broth. Binding of PHB granules to the nucleoid is mediated by PhaM, a PHB granule associated protein with phasin-like properties that is also able to bind to DNA and to phasin PhaP5. Over-expression of PhaM resulted in formation of many small PHB granules that were always attached to the nucleoid region. In contrast, PHB granules of ∆phaM strains became very large and distribution of granules to daughter cells was impaired. Association of PHB granules to the nucleoid region was prevented by over-expression of PhaP5 and clusters of several PHB granules were mainly localized near the cell poles. Conclusion Subcellular localization of PHB granules is controlled in R. eutropha and depends on the presence and concentrations of at least two PHB granule associated proteins, PhaM and PhaP5.

Abstract Background At present there is no consensus on irradiation treatment volumes for intermediate to high-risk primary cancers or recurrent disease. Conventional imaging modalities, such as CT, MRI and transrectal ultrasound, are considered suboptimal for treatment decisions. Choline-PET/CT might be considered as the imaging modality in radiooncology to select and delineate clinical target volumes extending the prostate gland or prostate fossa. In conjunction with intensity modulated radiotherapy (IMRT) and imaged guided radiotherapy (IGRT), it might offer the opportunity of dose escalation to selected sites while avoiding unnecessary irradiation of healthy tissues. Methods Twenty-six patients with primary (n = 7) or recurrent (n = 19) prostate cancer received Choline-PET/CT planned 3D conformal or intensity modulated radiotherapy. The median age of the patients was 65 yrs (range 45 to 78 yrs). PET/CT-scans with F18-fluoroethylcholine (FEC) were performed on a combined PET/CT-scanner equipped for radiation therapy planning. The majority of patients had intermediate to high risk prostate cancer. All patients received 3D conformal or intensity modulated and imaged guided radiotherapy with megavoltage cone beam CT. The median dose to primary tumours was 75.6 Gy and to FEC-positive recurrent lymph nodal sites 66,6 Gy. The median follow-up time was 28.8 months. Results The mean SUVmax in primary cancer was 5,97 in the prostate gland and 3,2 in pelvic lymph nodes. Patients with recurrent cancer had a mean SUVmax of 4,38. Two patients had negative PET/CT scans. At 28 months the overall survival rate is 94%. Biochemical relapse free survival is 83% for primary cancer and 49% for recurrent tumours. Distant disease free survival is 100% and 75% for primary and recurrent cancer, respectively. Acute normal tissue toxicity was mild in 85% and moderate (grade 2) in 15%. No or mild late side effects were observed in the majority of patients (84%). One patient had a severe bladder shrinkage (grade 4) after a previous treatment with TUR of the prostate and seed implantation. Conclusions FEC-PET/CT planning could be helpful in dose escalation to lymph nodal sites of prostate cancer.

Abstract Background Several studies have shown an association of cryptogenic stroke and embolism with patent foramen ovale (PFO), but the question how to prevent further events in such patients is unresolved. Options include antithrombotic treatment with warfarin or antiplatelet agents or surgical or endovascular closure of the PFO. The PC-Trial was set up to compare endovascular closure and best medical treatment for prevention of recurrent events. Methods The PC-Trial is a randomized clinical trial comparing the efficacy of percutaneous closure of the PFO using the Amplatzer PFO occluder with best medical treatment in patients with cryptogenic embolism, i.e. mostly cryptogenic stroke. Warfarin for 6 months followed by antiplatelet agents is recommended as medical treatment. Randomization is stratified according to patients age ( Discussion patients were randomized in 29 centers of Europe, Canada, and Australia. Randomization started February 2000. Enrollment of 414 patients was completed in February 2009. All patients will be followed-up longitudinally. Follow-up is maintained until the last enrolled patient is beyond 2.5 years of follow-up (expected in 2011). Trial Registration Trial listed in ClinicalTrials.gov as NCT00166257 and sponsored by AGA Medical, Plymouth, MN, USA

Introduction: The patent foramen ovale (PFO) is a common anatomical variant in humans (prevalence 25%). Most often asymptomatic, it may engender paradoxically embolic strokes, myocardial infarctions, or visceral or peripheral ischemia. It is causatively related to migraine, positional or exertional hypoxemia with dyspnea, diving incidents, high altitude edema, and sleep apnea. Percutaneous closure of atrial septal defects was first performed in the seventies. A dedicated PFO occluder (Amplatzer PFO Occluder) was first used on 10 September 1997 by Kurt Amplatz and Bernhard Meier. Since, percutaneous PFO closure has evolved into one of the most common and the simplest and safest catheter-based intervention in adult cardiology. Randomized studies have proved its benefit for prevention of recurrent ischemic events (particularly strokes) in patients without competing stroke etiology. There are also supportive clinical data for PFO closure in other situations. Areas covered: The Amplatzer PFO Occluder, the first, most implanted, and best-studied PFO occluder, is reviewed, presenting implantation technique, possible complications, and pertinent scientific data of efficacy and safety. Expert commentary: Percutaneous PFO closure has grown to one of the most common procedures in interventional cardiology. Implantation of the Amplatzer PFO Occluder is simple, safe, and effective. [ABSTRACT FROM AUTHOR]