Search

Angiotensin II type 1 receptors (AT1R) blocker losartan is used in patients with renal and cardiovascular diseases. [18F]fluoropyridine‐losartan has shown favorable binding profile for quantitative renal PET imaging of AT1R with selective binding in rats and pigs, low interference of radiometabolites and appropriate dosimetry for clinical translation. A new approach was developed to produce [18F]fluoropyridine‐losartan in very high molar activity. Automated radiosynthesis was performed in a three‐step, two‐pot, and two‐HPLC‐purification procedure within 2 h. Pure [18F]FPyKYNE was obtained by radiofluorination of NO2PyKYNE and silica‐gel‐HPLC purification (40 ± 9%), preventing the formation of nitropyridine‐losartan in the second step. Conjugation with trityl‐losartan azide via click chemistry, followed by acid hydrolysis, C18‐HPLC purification and reformulation provided [18F]fluoropyridine‐losartan in 11 ± 2% (decay‐corrected from [18F]fluoride, EOB). Using tris[(1‐(3‐hydroxypropyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl]‐amine (THPTA) as a Cu(I)‐stabilizing agent for coupling [18F]FPyKYNE to the unprotected losartan azide afforded [18F]fluoropyridine‐losartan in similar yields (11 ± 3%, decay‐corrected from [18F]fluoride, EOB). Reverse‐phase HPLC was optimized by reducing the pH of the mobile phase to achieve complete purification and high molar activities (467 ± 60 GBq/μmol). The use of radioprotectants prevented tracer radiolysis for 10 h (RCP > 99%). The product passed the quality control testing. This reproducible automated radiosynthesis process will allow in vivo PET imaging of AT1R expression in several diseases. [ABSTRACT FROM AUTHOR]

Background: Noninvasive vascular strain imaging under conventional line‐by‐line scanning has a low frame rate and lateral resolution and depends on the coordinate system. It is thus affected by high deformations due to image decorrelation between frames. Purpose: To develop an ultrafast time‐ensemble regularized tissue‐Doppler optical‐flow principal strain estimator for aorta deformability assessment in a long‐axis view. Methods: This approach alleviated the impact of lateral resolution using image compounding and that of the coordinate system dependency using principal strain. Accuracy and feasibility were evaluated in two aorta‐mimicking phantoms first, and then in four age‐matched individuals with either a normal aorta or a pathological ascending thoracic aorta aneurysm (TAA). Results: Instantaneous aortic maximum and minimum principal strain maps and regional accumulated strains during each cardiac cycle were estimated at systolic and diastolic phases to characterize the normal aorta and TAA. In vitro, principal strain results matched sonomicrometry measurements. In vivo, a significant decrease in maximum and minimum principal strains was observed in TAA cases, whose range was respectively 7.9 ± 6.4% and 8.2 ± 2.6% smaller than in normal aortas. Conclusions: The proposed principal strain estimator showed an ability to potentially assess TAA deformability, which may provide an individualized and reliable evaluation method for TAA rupture risk assessment. [ABSTRACT FROM AUTHOR]

Neprilysin, also known as neutral endopeptidase, is a cell surface membrane metalo‐endopeptidase that cleaves various peptides. Altered neprilysin expression has been correlated with various cancers and cardiovascular diseases. In this work, we present the radiosynthesis of the novel O‐11C‐methylated derivative of LBQ657 (a potent neprilysin inhibitor). (2R,4S)‐5‐(Biphenyl‐4‐yl)‐4‐[(3‐carboxypropionyl)amino]‐2‐methylpentanoic acid [11C]methyl ester ([11C]MeOLBQ) is an analog of sacubitril where the alkyl ester is a 11C‐methyl instead of an ethyl. [11C]MeOLBQ was produced in a one‐pot two‐step synthesis. The O‐11C‐methylation of the pentanoic acid part was done with [11C]methyl triflate followed by the deprotection of the tert‐butyl ester precursor in acidic conditions. [11C]MeOLBQ ([11C]7) was produced in 9.5 ± 2.5% RCY (25 ± 6% decay‐corrected from [11C]CO2, n = 3) high molar activity 348 ± 100 GBq/μmol (9425 ± 2720 mCi/μmol) at EOS, in high chemical (>95%) and radiochemical (>99%) purities. The total synthesis time including HPLC purification and reformulation was 29 minutes. To our knowledge, this is the first PET‐labeled analog of the clinically used NEP inhibitor sacubitril. [ABSTRACT FROM AUTHOR]

Aims: Bromocriptine is thought to facilitate left ventricular (LV) recovery in peripartum cardiomyopathy (PPCM) through inhibition of prolactin secretion. However, this potential therapeutic effect remains controversial and was incompletely studied in diverse populations. Methods and results: Consecutive women with new‐onset PPCM (n = 76) between 1994 and 2015 in Quebec, Canada, were classified according to treatment (n = 8, 11%) vs. no treatment (n = 68, 89%) with bromocriptine. We assessed LV functional recovery at mid‐term (6 months) and long‐term (last follow‐up) and compared outcomes among groups. Women treated with bromocriptine experienced better mid‐term left ventricular ejection fraction (LVEF) recovery from 23 ± 10% at baseline to 55 ± 12% at 6 months, compared with a change from 30 ± 12% at baseline to 45 ± 13% at 6 months in women treated with standard medical therapy (P interaction < 0.01). At long‐term, a similar positive association was found with bromocriptine (9% greater LVEF variation, P interaction < 0.01). In linear regressions adjusted for obstetrical, clinical, echocardiographic, and pharmacological variables, treatment with bromocriptine was associated with a greater improvement in LVEF [β coefficient (standard error), 14.1 (4.4); P = 0.03]. However, there was no significant association between bromocriptine use and the combined occurrence of all‐cause death and heart failure events (hazard ratio, 1.18; 95% confidence interval, 0.15 to 9.31), using univariable Cox regressions based over a cumulative follow‐up period of 285 patient‐years. Conclusions: In women newly diagnosed with PPCM, treatment with bromocriptine was independently associated with greater LV functional recovery. [ABSTRACT FROM AUTHOR]

The protective action of remote ischaemic preconditioning (RIPC) has been demonstrated in the context of surgical interventions in cardiology. Application of RIPC to sports performance has been proposed, but its effect on the electrocardiogram (ECG) during exercise remains unknown. This exploratory study aims to measure the changes in ventricular repolarization observed during exercise following RIPC in healthy subjects. In an experimental randomized crossover study, 17 subjects underwent two bouts of constant load exercise tests at 75% and 115% of gas exchange threshold (GET). Prior to exercise, they were allocated to either control or RIPC intervention with four cycles of 5 min of ischaemia followed by 5 min of reperfusion. ECG was continuously recorded during the protocol. QT and RR intervals were measured every 30 s (on an average tracing of the preceding 10 s). Although the time course of RR intervals did not differ between the two interventions (p = .56 at 75% GET andp = .74 at 115% GET), a significant shortening of QT intervals (measured from Q onset to T end) was observed during exercise (mean ± standard deviation of RIPC vs. control: −32 ± 19 ms at 75% GET (p < .001) and −34 ± 12 ms at 115% GET (p < .001)) as well as during recovery (−21 ± 8 ms at 75% GET (p < .001) and −16 ± 11 ms at 115% GET (p < .001)). This effect was not present at rest. These RIPC-related changes were clearly identifiable on the QT–RR loops after hysteresis reduction. RIPC therefore induces heart rate-independent shortening of QT intervals that is revealed during exercise. [ABSTRACT FROM PUBLISHER]

The article offers information on the integrating functions of cardiac resynchronization therapy. It discusses that first step to integrate image for cardiac resynchronization therapy is to build a three dimensional regional mechanical dyssnchrony map. It presents a image of velocities recorded during the systole in normal myocardium. It also presents a pilot study where Doppler echocardiography was performed in patients eligible for CRT within 24 hours before device implantation.

Background: Cardiac resynchronization therapy (CRT) improves heart failure (HF) symptoms through a reduction of cardiac mechanical dyssynchrony. Mechanical dyssynchrony is currently estimated by electrical dyssynchrony (QRS duration). It is known that electrical and mechanical dyssynchrony are not well correlated in HF patients. However, there is limited information about whether this relationship might be influenced by the underlying cardiomyopathy. Methods: Doppler echocardiography was performed in 88 patients presenting with heart failure due to ischemic (n = 42) or nonischemic (n = 46) heart disease, left ventricular ejection fraction <40%, New York Heart Association class II–IV, regardless of their QRS duration. Interventricular dyssynchrony was assessed by the time interval between preaortic and prepulmonary ejection times. Intraventricular dyssynchrony was ascertained by (1) the delay between the earliest and the latest peak negative longitudinal strain recorded in the basal and mid-segments of the lateral and septal walls (TMinMax) and (2) the standard deviation of time-to-peak in the same segments (SDdys). Results: The correlation coefficient between QRS duration and mechanical interventricular dyssynchrony was r = 0.47 (P < 0.001) in patients with nonischemic disease and nonsignificant in patients with ischemic disease. Similarly, the correlation coefficient between QRS duration and mechanical intraventricular dyssynchrony was significant in patients with nonischemic disease (r = 0.37, P = 0.01 for TMinMax; r = 0.42, P = 0.003 for SDdys) and nonsignificant in patients with ischemic disease. Conclusion: The concordance between electrical dyssynchrony assessed by QRS duration and mechanical dyssynchrony assessed by myocardial strain is dependent upon the underlying cardiomyopathy. This observation may improve our understanding of the various responses observed in CRT patients. [ABSTRACT FROM AUTHOR]