Extracellular vesicles as circulating cancer biomarkers: opportunities and challenges.

Extracellular vesicles (EVs) are small, lipid-bound particles containing nucleic acid and protein cargo which are excreted from cells under a variety of normal and pathological conditions. EVs have garnered substantial research interest in recent years, due to their potential utility as circulating biomarkers for a variety of diseases, including numerous types of cancer. The following review will discuss the current understanding of the form and function of EVs, their specific role in cancer pathogenesis and their potential for non-invasive disease diagnosis and/or monitoring. This review will also highlight several key issues for this field, including the importance of implementing robust and reproducible sample handling protocols, and the challenge of extracting an EV-specific biomarker signal from a complex biological background.

Comparison of temporary bifocal right ventricular pacing and biventricular pacing for heart failure: evaluation by tissue Doppler imaging.

BACKGROUND: The complications and limitations of biventricular pacing largely relate to left ventricular (LV) pacing. An alternative approach was tested of simultaneously pacing the right ventricular (RV) apex and outflow tract (RVOT) or using bifocal right ventricular pacing (BRVP) to provide cardiac resynchronisation. METHODS: 21 consecutive patients with heart failure and severely impaired left ventricular function were studied. Ejection fraction and tissue Doppler data were collected at baseline, during BRVP, and during biventricular pacing, using a temporary pacing protocol. RESULTS: BRVP was achieved in all patients without complication. BRVP significantly reduced mean baseline intra-LV, inter-LV-RV, and global mechanical dyssynchrony from (mean (SD)) 71 (35) to 44 (18) ms, p = 0.003; 86 (42) to 57 (33) ms, p = 0.029; and 157 (67) to 101 (42) ms, p = 0.005, respectively. It increased the ejection fraction from 21 (8)% to 29 (7)%, p = 0.002. Compared with BRVP, reductions in intra-LV, inter-LV-RV, and global mechanical dyssynchrony were superior with biventricular pacing (31 (12) ms, p = 0.014; 36 (27) ms, p = 0.008; and 67 (34) ms, p = 0.01 compared with BRVP, respectively); improvements in ejection fraction were similar (26 (9)%, NS). CONCLUSIONS: In patients with heart failure, superior mechanical resynchronisation is achieved with biventricular pacing compared with BRVP. BRVP may be useful when left ventricular lead placement is not possible.

The interaction of interventricular pacing intervals and left ventricular lead position during temporary biventricular pacing evaluated by tissue Doppler imaging.

OBJECTIVE: To determine the effects of interventricular pacing interval and left ventricular (LV) pacing site on ventricular dyssynchrony and function at baseline and during biventricular pacing, using tissue Doppler imaging. METHODS: Using an angioplasty wire to pace the left ventricle, 20 patients with heart failure and left bundle branch block underwent temporary biventricular pacing from lateral (n = 20) and inferior (n = 10) LV sites at five interventricular pacing intervals: +80, +40, synchronous, -40, and -80 ms. RESULTS: LV ejection fraction (EF) increased (mean (SD) from 18 (8)% to 26 (10)% (p = 0.016) and global mechanical dyssynchrony decreased from 187 (91) ms to 97 (63) ms (p = 0.0004) with synchronous biventricular pacing compared to unpaced baseline. Sequential pacing with LV preactivation produced incremental improvements in EF and global mechanical dyssynchrony (p<0.0001 and p = 0.0026, respectively), primarily as a result of reductions in inter-LV-RV dyssynchrony (p = 0.0001) rather than intra-LV dyssynchrony (NS). Results of biventricular pacing from an inferior or lateral LV site were comparable (for example, synchronous biventricular pacing, global mechanical dyssynchrony: lateral LV site, 97 (63) ms; inferior LV site, 104 (41) ms (NS); EF: lateral LV site, 26 (10)%; inferior LV site, 27 (10)% (NS)). ECG morphology was identical during biventricular pacing through an angioplasty wire and a permanent lead. CONCLUSIONS: Sequential biventricular pacing with LV preactivation most often optimises LV synchrony and EF. An inferior LV site offers a good alternative to a lateral site. Pacing through an angioplasty wire may be useful in assessing the acute effects of pacing.

Echocardiographic methods for selecting patients suitable for biventricular pacing therapy.

The large outcome studies of biventricular pacing to date have selected patients using electrocardiogram criteria (prolonged QRS and left bundle branch block morphology). However, 20-30% of patients do not appear to respond clinically, and as a result there has been much interest in developing more specific methods of detecting mechanical dyssynchrony. A number of different echocardiographic techniques have been developed which appear to offer greater sensitivity and specificity than ECG in selecting these patients. This paper reviews the most promising of the echocardiographic techniques and gives guidance for the clinical use of echocardiography in selecting patients for biventricular pacing.

Selection and optimisation of biventricular pacing: the role of echocardiography.

The quantification of ventricular dyssynchrony is a key factor in identifying patients with severe heart failure who may benefit from cardiac resynchronisation with biventricular pacing (BVP). Echocardiographic techniques appear to offer superior sensitivity and specificity than the ECG in selecting these patients. This paper reviews the scope of current echocardiographic techniques for guiding both patient selection and optimisation of device programming following implantation.