Peter J. Pugh

Incidence of atrial fibrillation detected by implantable loop recorders in unexplained stroke

Objectives: The usefulness of the implantable loop recorder (ILR) with improved atrial fibrillation (AF) detection capability (Reveal XT) and the factors associated with AF in the setting of unexplained stroke were investigated. Methods: A cohort study is reported of 51 patients in whom ILRs were implanted for the investigation of ischemic stroke for which no cause had been found (cryptogenic) following appropriate vascular and cardiac imaging and at least 24 hours of cardiac rhythm monitoring. Results: The patients were aged from 17 to 73 (median 52) years. Of the 30 patients with a shunt investigation, 22 had a patent foramen ovale (73.3%; 95% confidence interval [CI] 56.5%–90.1%). AF was identified in 13 (25.5%; 95% CI 13.1%–37.9%) cases. AF was associated with increasing age (p = 0.018), interatrial conduction block (p = 0.02), left atrial volume (p = 0.025), and the occurrence of atrial premature contractions on preceding external monitoring (p = 0.004). The median (range) of monitoring prior to AF detection was 48 (0–154) days. Conclusion: In patients with unexplained stroke, AF was detected by ILR in 25.5%. Predictors of AF were identified, which may help to target investigations. ILRs may have a central role in the future in the investigation of patients with unexplained stroke.

Effect of Low-Amplitude Two-Dimensional Radial Strain at Left Ventricular Pacing Sites on Response to Cardiac Resynchronization Therapy

BACKGROUNDnLeft ventricular (LV) lead placement to areas of scar has detrimental effects on response to cardiac resynchronization therapy (CRT). Speckle-tracking radial two-dimensional strain offers assessment of the extent of regional myocardial deformation. The aim of this study was to assess the impact of LV lead placement at areas of low-amplitude strain on CRT response.nnnMETHODSnThe optimal cutoff of radial strain amplitude at the LV pacing site associated with an unfavorable CRT response was determined in a derivation group (n = 65) and then tested in a second consecutive validation group (n = 75) of patients with heart failure. Patients had concordant LV leads if placed at the most delayed site, and dyssynchrony was defined as anteroseptal to posterior delay ≥ 130 msec. CRT response was defined as a ≥15% reduction in LV end-systolic volume at 6 months.nnnRESULTSnIn the derivation group, a derived cutoff for radial strain amplitude of <9.8% defined low-amplitude segments (LAS) and had a high specificity but low sensitivity for predicting LV reverse remodeling, suggesting a strong negative predictive value. In the validation group, compared with patients without LAS at the LV pacing site, in patients with LAS (n = 16), CRT response was significantly lower (62.7% vs 31.3%, P < .05). By multivariate analysis, LV lead concordance and the absence of an LAS at the LV pacing site but not dyssynchrony were significantly related to CRT response.nnnCONCLUSIONnLV lead placement over segments with two-dimensional radial strain amplitudes <9.8% is associated with poor outcomes of CRT.

The Impact of the Right Ventricular Lead Position on Response to Cardiac Resynchronization Therapy

Introduction: Left ventricular (LV) lead placement to the latest contracting area (concordant LV lead) is associated with better response to cardiac resynchronization therapy (CRT) compared to a discordant LV lead. However, the effect of the right ventricular (RV) lead site on CRT response is unclear. We investigated the relationship of the RV and LV lead positions on CRT response.

Prognostic Benefit of Optimum Left Ventricular Lead Position in Cardiac Resynchronization Therapy : Follow-Up of the TARGET Study Cohort (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy)

OBJECTIVESnThis study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT).nnnBACKGROUNDnAn optimal LV lead position in CRT is associated with improved clinical outcome. A strategy of speckle-tracking echocardiography can be used to guide the implanter to the site of latest activation and away from segments of low strain amplitude (scar). Long-term, prospective survival data according to LV lead position in CRT are limited.nnnMETHODSnData from a follow-up registry of 250 consecutive patients receiving CRT between June 2008 and July 2010 were studied. The study population comprised patients recruited to the derivation group and the subsequent TARGET (Targeted Left Ventricular Lead Placement to guide Cardiac Resynchronization Therapy) randomized, controlled trial. Final LV lead position was described, in relation to the pacing site determined by pre-procedure speckle-tracking echocardiography, as optimal (concordant/adjacent) or suboptimal (remote). All-cause mortality was recorded at follow-up.nnnRESULTSnAn optimal LV lead position (n = 202) conferred LV remodeling response superior to that of a suboptimal lead position (change in LV end-systolic volume: -24 ± 15% vs. -12 ± 17% [p < 0.001]; change in ejection fraction: +7 ± 8% vs. +4 ± 7% [p = 0.02]). During long-term follow-up (median: 39 months; range: <1 to 61 months), an optimal LV lead position was associated with improved survival (log-rank p = 0.003). A suboptimal LV lead placement independently predicted all-cause mortality (hazard ratio: 1.8; p = 0.024).nnnCONCLUSIONSnAn optimal LV lead position at the site of latest mechanical activation, avoiding low strain amplitude (scar), was associated with superior CRT response and improved survival that persisted during follow-up.

Cardiac resynchronization therapy optimization using noninvasive cardiac output measurement.

Aims: u2002Noninvasive cardiac output (CO) measurement (NICOM) is a novel method to assess ventricular function and offers a potential alternative for optimization of cardiac resynchronization therapy (CRT) devices. We compared the effect of NICOM‐based optimization to no optimization (empiric settings) on CRT outcomes.

Non-invasive cardiac output measurements based on bioreactance for optimization of atrio- and interventricular delays.

AIMSnNon-invasive cardiac output monitoring (NICOM) based on bio-reactance offers a portable method to assess ventricular function. Optimization of cardiac resynchronization therapy (CRT) by echocardiography is labour-intensive. We compared the ability of NICOM and echocardiography to facilitate optimum CRT device programming.nnnMETHODS AND RESULTSnForty-seven patients in sinus rhythm were evaluated within 14 days of CRT implantation. The atrio- (AV) and interventricular (VV) delay intervals were incrementally adjusted and at each setting, NICOM and echocardiographic data were recorded. Left ventricular (LV) volumes and function were assessed by echocardiography at baseline and 3 months. Response to CRT was defined as a reduction in LV end-systolic volume (LVESV) by >15%. In all patients, cardiac output (CO) increased significantly at optimized settings compared with baseline (5.66 +/- 1.4 vs. 4.35 +/- 1.1 L/min, P < 0.001). A 20% increase in acute CO following CRT predicted LVESV reduction of >15% with a sensitivity of 81% and specificity of 92% (AUC 0.86). The optimum AV delay determined by NICOM was confirmed by echocardiography in 40 of 47 patients (85%, r = 0.89, P < 0.01) and for VV delay in 39 of 47 patients (83%, r = 0.89, P < 0.01).nnnCONCLUSIONnNon-invasive cardiac output monitoring is a simple, reliable, and portable alternative to echocardiography to program CRT devices.

Radial Strain Delay Based on Segmental Timing and Strain Amplitude Predicts Left Ventricular Reverse Remodeling and Survival After Cardiac Resynchronization Therapy

Background— Dyssynchrony assessment based on the timing of regional contraction is inherently independent of underlying myocardial contractility. We tested the hypothesis that patient selection for cardiac resynchronization therapy (CRT) would be enhanced using a parameter derived from the net radial strain delay (RSD) for the 12 basal and mid–left ventricular segments (calculated radial strain delay RSD [RSDc]), based on not only timing but also amplitude of segmental strain. Methods and Results— Echocardiographic data were analyzed in 240 patients with symptomatic heart failure undergoing CRT (New York Heart Association class III/IV; QRS >120 milliseconds; ejection fraction, 23±7%). RSDc was calculated as the sum of difference between peak radial strain and radial strain at aortic valve closure before CRT implantation. CRT response was defined as >15% reduction in left ventricular end-systolic volume at 6 months. In a derivation group (n=102), RSDc was higher in responders compared with nonresponders (74±39% versus 29±15%; P<0.001) and related to the change in left ventricular end-systolic volume (r=−0.53; P<0.001). RSDc >40% predicted remodeling (sensitivity, 87%; specificity, 88%). In the validation group (n=108), RSDc similarly predicted response (sensitivity, 89%; specificity, 84%). Survival at long-term follow-up was greater in patients with RSDc >40% (P<0.0001). Conclusions— RSDc, based on both the timing and the amplitude of segmental strain, has a strong predictive value for CRT remodeling response and long-term survival.

Impact of VV optimization in relation to left ventricular lead position: an acute haemodynamic study

AIMSnLeft ventricular (LV) lead placement to the most delayed segment offers the greatest potential benefit to cardiac resynchronization therapy (CRT). We assessed the impact of interventricular (VV) optimization on acute changes in cardiac output (CO) in patients with and without LV pacing of the most delayed segment.nnnMETHODS AND RESULTSnIn 124 patients, the most delayed segment was defined by speckle tracking radial strain and the LV lead position by biplane fluoroscopy. Patients were classified as either a concordant (LV lead at latest site), adjacent (within one segment), or remote (two or more segments away) LV lead. Atrioventricular (AV) and VV delays were optimized by echocardiography. Cardiac output was measured non-invasively and a >20% increase in CO from baseline (intrinsic) defined acute response. Changes in CO in patients with concordant, adjacent, or remote LV leads were recorded following atrioventricular optimization alone (AV OPT) and after combined AV and VV optimization (AV/VV OPT). Compared with AV OPT pacing, AV/VV OPT produced a greater rise in CO (5.45 ± 1.1 vs. 5.76 ± 1.2 L/min, P< 0.001) and higher acute response rates (48.4 vs. 61.3%, P= 0.041). In adjacent patients, compared with AV OPT pacing, AV/VV OPT settings increased the response rate from 36.4 to 63.6% (P= 0.037). VV optimization had no effect on acute response rates in patients with remote (26.7 vs. 33.3%, P = 0.581) or concordant LV leads (65.6 vs. 72.1%, P = 0.438).nnnCONCLUSIONnVV optimization overcomes some but not all of the deleterious effects of a suboptimal LV lead position.

Increased incidence of interatrial block in younger adults with cryptogenic stroke and patent foramen ovale.

Background: Stroke is often unexplained in younger adults, although it is often associated with a patent foramen ovale (PFO). The reason for the association is not fully explained, and mechanisms other than paradoxical embolism may be involved. Young stroke patients with PFO have more atrial vulnerability than those without PFO. It is plausible that stretching of the interatrial septum may disrupt the interatrial conduction pathways causing interatrial block (IAB). IAB is associated with atrial fibrillation, dysfunctional left atria and stroke. Methods: Electrocardiogram (ECG) characteristics of prospectively recruited young patients (≤55 years of age) with unexplained stroke (TOAST and A-S-C-O) were compared with control data. All stroke cases underwent bubble contrast transthoracic and transoesophageal echography. IAB was defined as a P-wave duration of ≧110 ms. ECG data were converted to electronic format and analysed in a blind manner. Results: Fifty-five patients and 23 datasets were analysed. Patients with unexplained stroke had longer P-wave duration (p = 0.013) and a greater prevalence of IAB (p = 0.02) than healthy controls. Case status was an independent predictor of P-wave duration in a significant multivariate model. There was a significant increase in the proportion of cases with a PFO with IAB compared with cases without PFO and with controls (p = 0.005). Conclusions: Young patients with unexplained stroke, particularly those with PFO, exhibit abnormal atrial electrical characteristics suggesting atrial arrhythmia or atrial dysfunction as a possible mechanism of stroke.

Development of a multiparametric score to predict left ventricular remodelling and prognosis after cardiac resynchronization therapy

Optimal delivery of CRT requires appropriate patient selection and device implantation. Echocardiographic predictors of CRT response individually appear to enhance patient selection, but do not fully reflect the complex underlying myocardial dysfunction. We hypothesized that a multiparametric approach would offer greater predictive value and sought to derive a score incorporating baseline characteristics including: dyssynchrony, LV function, and LV lead position.