Current Role of Electrocardiographic Imaging in Patient Selection for Cardiac Resynchronization Therapy.

Cardiac resynchronization therapy (CRT) is a recognized therapy for heart failure with altered ejection fraction and abnormal left ventricular activation time. Since the introduction of the therapy, a 30% rate of non-responders is observed and unchanged. The 12-lead ECG remains the only recommended tool for patient selection to CRT.

Pacing therapy for atrioventricular dromotropathy: a combined computational-experimental-clinical study.

Aims: Investigate haemodynamic effects, and their mechanisms, of restoring atrioventricular (AV)-coupling using pacemaker therapy in normal and failing hearts in a combined computational-experimental-clinical study.

Methods And Results: Computer simulations were performed in the CircAdapt model of the normal and failing human heart and circulation. Experiments were performed in a porcine model of AV dromotropathy.

Left-axis deviation in patients with nonischemic heart failure and left bundle branch block is a purely electrical phenomenon.

Background: Possible mechanisms of left-axis deviation (LAD) in the setting of left bundle branch block (LBBB) include differences in cardiac electrophysiology, structure, or anatomic axis.

Objective: The purpose of this study was to clarify the mechanism(s) responsible for LAD in patients with LBBB.

Methods: Twenty-nine patients with nonischemic cardiomyopathies and LBBB underwent noninvasive electrocardiographic imaging (ECGi), cardiac computed tomography, and magnetic resonance imaging in order to define ventricular electrical activation, characterize cardiac structure, and determine the cardiac anatomic axis.

Interim Analysis of the Phase II Study: Noninferiority Study of Doxorubicin with Upfront Dexrazoxane plus Olaratumab for Advanced or Metastatic Soft-Tissue Sarcoma.

Purpose: To report the interim analysis of the phase II single-arm noninferiority trial, testing the upfront use of dexrazoxane with doxorubicin on progression-free survival (PFS) and cardiac function in soft-tissue sarcoma (STS).

Patients And Methods: Patients with metastatic or unresectable STS who were candidates for first-line treatment with doxorubicin were deemed eligible. An interim analysis was initiated after 33 of 65 patients were enrolled.

Prognostic Utility of Echocardiographic Atrial and Ventricular Strain Imaging in Patients With Cardiac Amyloidosis.

Objectives: The prognostic value of echocardiographic atrial and ventricular strain imaging in patients with biopsy-proven cardiac amyloidosis was assessed.

Background: Although left ventricular global longitudinal strain (GLS) is known to be predictive of outcome, the additive prognostic value of left (LA), right atrial (RA), and right ventricular (RV) strain is unclear.

Methods: One hundred thirty-six patients with cardiac amyloidosis and available follow-up data were studied by endomyocardial biopsy, noncardiac biopsy with supportive cardiac imaging, or autopsy confirmation.

The Left and Right Ventricles Respond Differently to Variation of Pacing Delays in Cardiac Resynchronization Therapy: A Combined Experimental- Computational Approach.

Timing of atrial, right (RV), and left ventricular (LV) stimulation in cardiac resynchronization therapy (CRT) is known to affect electrical activation and pump function of the LV. In this study, we used computer simulations, with input from animal experiments, to investigate the effect of varying pacing delays on both LV and RV electrical dyssynchrony and contractile function. A pacing protocol was performed in dogs with atrioventricular block ( = 6), using 100 different combinations of atrial (A)-LV and A-RV pacing delays.

Distinct lipid droplet characteristics and distribution unmask the apparent contradiction of the athlete's paradox.

Objective: Intramyocellular lipid (IMCL) storage negatively associates with insulin resistance, albeit not in endurance-trained athletes. We investigated the putative contribution of lipid droplet (LD) morphology and subcellular localization to the so-called athlete's paradox.

Methods: We performed quantitative immunofluorescent confocal imaging of muscle biopsy sections from endurance Trained, Lean sedentary, Obese, and Type 2 diabetes (T2DM) participants (n = 8/group).

Response to cardiac resynchronization therapy is determined by intrinsic electrical substrate rather than by its modification.

Background: Electrocardiographic mapping (ECM) expresses electrical substrate through magnitude and direction of the activation delay vector (ADV). We investigated to what extent the response to cardiac resynchronization therapy (CRT) is determined by baseline ADV and by ADV modification through CRT and optimization of left ventricular (LV) pacing site.

Methods: ECM was performed in 79 heart failure patients (4 RBBB, 12 QRS < 120 ms, 23 non-specific conduction delay [NICD] and 40 left bundle branch block [LBBB]).

Electrical Substrates Driving Response to Cardiac Resynchronization Therapy: A Combined Clinical-Computational Evaluation.

Background: The predictive value of interventricular versus intraventricular dyssynchrony for response to cardiac resynchronization therapy (CRT) remains unclear. We investigated the relative importance of both ventricular electrical substrate components for left ventricular (LV) hemodynamic function.

Methods And Results: First, we used the cardiovascular computational model CircAdapt to characterize the isolated effect of intrinsic interventricular and intraventricular activation on CRT response (ΔLVdP/dt).

Cardiac electrical dyssynchrony is accurately detected by noninvasive electrocardiographic imaging.

Background: Poor identification of electrical dyssynchrony is postulated to be a major factor contributing to the low success rate for cardiac resynchronization therapy.

Objective: The purpose of this study was to evaluate the sensitivity of body surface mapping and electrocardiographic imaging (ECGi) to detect electrical dyssynchrony noninvasively.

Methods: Langendorff-perfused pig hearts (n = 11) were suspended in a human torso-shaped tank, with left bundle branch block (LBBB) induced through ablation.

Dissociation of intramyocellular lipid storage and insulin resistance in trained athletes and type 2 diabetes patients; involvement of perilipin 5?

Key Points: Intramyocellular lipid storage is negatively associated with insulin sensitivity. However, endurance trained athletes and type 2 diabetes mellitus (T2DM) patients store similar amounts of lipids in their muscle; the so-called athlete's paradox. Compared to T2DM, trained athletes possess higher levels of perilipin 5 (PLIN5), a lipid droplet (LD) coating protein.

Cardiovascular magnetic resonance features of mechanical dyssynchrony in patients with left bundle branch block.

Patients with left bundle branch block (LBBB) can exhibit mechanical dyssynchrony which may contribute to heart failure; such patients may benefit from cardiac resynchronization treatment (CRT). While cardiac magnetic resonance imaging (CMR) has become a common part of heart failure work-up, CMR features of mechanical dyssynchrony in patients with LBBB have not been well characterized. This study aims to investigate the potential of CMR to characterize mechanical features of LBBB.

Septal flash and septal rebound stretch have different underlying mechanisms.

Abnormal left-right motion of the interventricular septum in early systole, known as septal flash (SF), is frequently observed in patients with left bundle branch block (LBBB). Transseptal pressure gradient and early active septal contraction have been proposed as explanations for SF. Similarities in timing (early systole) and location (septum) suggest that SF may be related to septal systolic rebound stretch (SRSsept).

Differentiating Electromechanical From Non-Electrical Substrates of Mechanical Discoordination to Identify Responders to Cardiac Resynchronization Therapy.

Background: Left ventricular (LV) mechanical discoordination, often referred to as dyssynchrony, is often observed in patients with heart failure regardless of QRS duration. We hypothesized that different myocardial substrates for LV mechanical discoordination exist from (1) electromechanical activation delay, (2) regional differences in contractility, or (3) regional scar and that we could differentiate electromechanical substrates responsive to cardiac resynchronization therapy (CRT) from unresponsive non-electrical substrates.

Methods And Results: First, we used computer simulations to characterize mechanical discoordination patterns arising from electromechanical and non-electrical substrates and accordingly devise the novel systolic stretch index (SSI), as the sum of posterolateral systolic prestretch and septal systolic rebound stretch.

Influence of left ventricular lead position relative to scar location on response to cardiac resynchronization therapy: a model study.

Aims: It is unclear how the position of the left ventricular (LV) lead relative to a scar affects the haemodynamic response in patients with dyssynchronous heart failure receiving cardiac resynchronization therapy. We investigated this complex interaction using a computational model.

Methods And Results: The CircAdapt computational cardiovascular system model was used to simulate heart failure with left bundle branch block (LBBB).