Endovascular renal sympathetic denervation to improve heart failure with reduced ejection fraction: the IMPROVE-HF-I study.

INTRODUCTION: The aim of the present study was to assess the safety and efficacy of renal sympathetic denervation (RDN) in patients with heart failure with reduced ejection fraction (HFrEF). METHODS: We randomly assigned 50 patients with a left ventricular ejection fraction (LVEF) ≤ 35% and NYHA class ≥ II, in a 1:1 ratio, to either RDN and optimal medical therapy (OMT) or OMT alone. The primary safety endpoint was the occurrence of a combined endpoint of cardiovascular death, rehospitalisation for heart failure, and acute kidney injury at 6 months. The primary efficacy endpoint was the change in iodine-123 meta-iodobenzylguanidine (123I­MIBG) heart-to-mediastinum ratio (HMR) at 6 months. RESULTS: Mean age was 60 ± 9 years, 86% was male and mean LVEF was 33 ± 8%. At 6 months, the primary safety endpoint occurred in 8.3% vs 8.0% in the RDN and OMT groups, respectively (p = 0.97). At 6 months, the mean change in late HMR was -0.02 (95% CI: -0.08 to 0.12) in the RDN group, versus -0.02 (95% CI: -0.09 to 0.12) in the OMT group (p = 0.95) whereas the mean change in washout rate was 2.34 (95% CI: -6.35 to 1.67) in the RDN group versus -2.59 (95% CI: -1.61 to 6.79) in the OMT group (p-value 0.09). CONCLUSION: RDN with the Vessix system in patients with HFrEF was safe, but did not result in significant changes in cardiac sympathetic nerve activity at 6 months as measured using 123I­MIBG.

Measuring left ventricular mechanical dyssynchrony from ECG-gated SPECT myocardial perfusion imaging.

Cardiac resynchronization therapy (CRT) has shown benefits in patients with severe heart failure. The traditional criteria to select patients for CRT (New York Heart Association [NYHA] class III or IV, depressed left ventricular [LV] ejection fraction, and prolonged QRS duration) result in at least 30% of the selected patients with no response to CRT. Recent studies with echocardiography have shown that the presence of LV dyssynchrony is an important predictor for response to CRT. However, the recent report from the predictors of response to cardiac resynchronization therapy (PROSPECT) trial suggested that under ''real-world'' conditions the current available echocardiographic techniques including tissue Doppler imaging (TDI) and myocardial strain-rate imaging are not ready for routine clinical practice to assess LV dyssynchrony. Phase analysis is a recently developed technique that allows measuring LV dyssynchrony from electrocardiogram (ECG)-gated single photon emission computed tomography (GSPECT) myocardial perfusion imaging (MPI). This technique uses Fourier harmonic functions to approximate regional wall thickening over the cardiac cycle and to calculate regional onset of mechanical contraction (OMC) phases. These OMC phases are obtained three-dimensionally over the entire left ventricle to quantitatively assess the degree of LV dyssynchrony. This technique has been compared to TDI and shown promising results in clinical validations. The advantages of this technique over echocardiography in measuring LV dyssynchrony are its automation, its high repeatability and reproducibility. It can be applied to any conventional GSPECT MPI study with no additional procedure. In this review the phase analysis methodology is described and its up-to-date clinical validations are summarized.

Non-invasive anatomical and functional imaging for the detection of coronary artery disease.

Coronary artery disease (CAD) is still an important cause of morbidity and mortality in the Western world. The gold standard for assessing significant coronary artery stenosis is invasive coronary angiography. Several disadvantages of the technique in combination with the fact that a substantial number of patients referred for conventional angiography appear free from significant stenosis have led to the pursuit of non-invasive imaging modalities for the diagnosis of CAD. The traditional modalities for this purpose are gated single-photon emission computed tomography, position emission tomography, (contrast) stress echocardiography and cardiac magnetic resonance (CMR), and these techniques can be characterized as functional imaging techniques as they detect ischaemia. Although the presence of a flow-limiting stenosis can be adequately ruled out with these techniques, atherosclerosis cannot be visualized with functional techniques. For this purpose, non-invasive coronary angiography techniques (computed tomography and CMR) are currently under development. The purpose of this review is to provide the reader an overview of the currently used imaging modalities to detect CAD.

Comprehensive cardiac assessment with multislice computed tomography: evaluation of left ventricular function and perfusion in addition to coronary anatomy in patients with previous myocardial infarction.

OBJECTIVE: To evaluate a comprehensive multislice computed tomography (MSCT) protocol in patients with previous infarction, including assessment of coronary artery stenoses, left ventricular (LV) function and perfusion. PATIENTS AND METHODS: 16-slice MSCT was performed in 21 patients with previous infarction; from the MSCT data, coronary artery stenoses, (regional and global) LV function and perfusion were assessed. Invasive coronary angiography and gated single-photon emission computed tomography (SPECT) served as the reference standards for coronary artery stenoses and LV function/perfusion, respectively. RESULTS: 236 of 241 (98%) coronary artery segments were interpretable on MSCT. The sensitivity and specificity for detection of stenoses were 91% and 97%. Pearson's correlation showed excellent agreement for assessment of LV ejection fraction between MSCT and SPECT (49 (13)% v 53 (12)%, respectively, r = 0.85). Agreement for assessment of regional wall motion was excellent (92%, kappa = 0.77). In 68 of 73 (93%) segments, MSCT correctly identified a perfusion defect as compared with SPECT, whereas the absence of perfusion defects was correctly detected in 277 of 284 (98%) segments. CONCLUSIONS: MSCT permits accurate, non-invasive assessment of coronary artery stenoses, LV function and perfusion in patients with previous infarction. All parameters can be assessed from a single dataset.

Infiltration by alien predators into invertebrate food webs in Hawaii: a molecular approach.

Abstract Alien invertebrate predators have been introduced to Hawaii to control pests, particularly in lowland areas where most crops are grown. We developed techniques for assessing the impact of these predators on native food webs in relatively pristine upland areas where, it was hypothesized, few lowland predators might be found. Predator densities were assessed along transects within the Alakaii Swamp on Kaua'i. The most numerous alien biocontrol agents found were Halmus chalybeus (Coccinellidae), a species known to feed on Lepidoptera eggs. Laboratory experiments were conducted using two genera of endemic Lepidoptera, Scotorythra and Eupithecia (Geometridae), that are of considerable conservation value, the former because of its recent speciation across Hawaii, the latter for its unique predatory larvae. Techniques were developed for detecting Lepidoptera DNA within the guts of alien predators using prey-specific PCR primers. General primers amplified fragments of the mitochondrial cytochrome oxidase I gene from beetles and Lepidoptera. The sequences were aligned and used successfully to design target-specific primers for general detection of the remains of Geometridae and for particular species, including Scotorythra rara and Eupithecia monticolans. DNA fragments amplified were short [140-170 base pairs (bp)], optimizing detection periods following prey ingestion. Trials using the introduced biocontrol agent Curinus coeruleus (Coccinellidae) demonstrated detection of Lepidoptera DNA fragments = 151 bp in 85-100% of beetles after 24 h digestion of an early instar larva. This study provides a framework for future use of molecular gut analysis in arthropod conservation ecology and food web research with considerable potential for quantifying threats to endemic species in Hawaii and elsewhere.

Response to walnut olfactory and visual cues by the parasitic wasp Diachasmimorpha juglandis.

Diachasmimorpha juglandis is a specialist parasitoid attacking fly larvae in the genus Rhagoletis that feed exclusively on walnut fruit husks. In a free-foraging assay comparing response to uninfested, infested, and mechanically damaged fruits, we first determined that D. juglandis use host feeding damage on the fruit as a cue for host presence. In another free-foraging assay that used artificial walnut models and wind tunnel experiments, D. juglandis distinguished infested from uninfested fruits by using either olfactory or visual cues separately. However, the response rate of wasps in the wind tunnel was raised considerably when visual cues were also available. We analyzed the volatile compounds emitted by cohorts of uninfested, mechanically damaged, and infested fruits 1, 3, 5, 8, and 10 days after oviposition by flies into the infested fruits. Total volatile emissions did not differ significantly among treatments, but quantitative changes in volatiles distinguished infested fruits from uninfested and damaged fruits. The fact that parasitoids did not distinguish between infested and damaged fruits in assays where damage was visible indicates that they rely on visual cues when those are available.

Infiltration of a Hawaiian community by introduced biological control agents.

To examine the community-wide effects of introduced biocontrol agents on Kauai Island, Hawaii, we constructed quantitative food webs showing interactions among plants, moths, and moth parasitoids in a native forest. Eighty-three percent of parasitoids reared from native moths were biological control agents, 14% were accidental immigrants, and 3% were native species. Although parasitism by biological control agents reached 28% in some species of moth, all biocontrol agents reared had been released before 1945. This study highlights the importance of considering the potential damage caused by an introduced control agent, in addition to that caused by the target alien species.