Left atrial appendage occlusion with the Amplatzer™ Amulet™ device: full results of the prospective global observational study.

AIMS: To evaluate the safety and efficacy of left atrial appendage occlusion (LAAO) with the Amplatzer™ Amulet™ occluder. METHODS AND RESULTS: Patients with atrial fibrillation eligible for LAAO were recruited to a prospective global study. Implant procedures were undertaken with echocardiographic guidance. Transoesophageal echocardiography (TOE) was undertaken 1-3 months post-LAAO. Implant and follow-up TOEs were evaluated by a CoreLab. The primary endpoint was a composite of ischaemic stroke and cardiovascular death at 2 years. Serious adverse events were adjudicated by an independent clinical events committee. A total of 1088 patients were enrolled, aged 75.2 ± 8.5 years; 64.5% were male. CHA2DS2-VASc and HAS-BLED scores were 4.2 ± 1.6 and 3.3 ± 1.1, respectively. A total of 71.7% had prior major bleeding, and 82.8% had contraindications to oral anticoagulants. Implant success was 99.1%. Major adverse events (≤7 days post-procedure) occurred in 4.0%, including death (0.3%), stroke (0.4%), major vascular (1.3%), and device embolization (0.2%). A total of 80.2% of patients were discharged on antiplatelet therapy alone. Peridevice flow was <3 mm in 98.4% at follow-up TOE. Device-related thrombus (DRT) was seen in 1.6% of cases. Cardiovascular death or ischaemic stroke occurred in 8.7% of patients at 2 years. The ischaemic stroke rate was 2.2%/year-a 67% reduction compared to the CHA2DS2-VASc predicted rate. Major bleeding (Bleeding Academic Research Consortium type ≥ 3) occurred at rates of 10.1%/year (year 1) and 4.0%/year (year 2). CONCLUSION: Following LAAO with the Amplatzer Amulet device, the ischaemic stroke rate was reduced by 67% compared to the predicted risk. Closure was complete in 98.4% of cases and DRT seen in only 1.6%.

Safety and Efficacy Outcomes of Combined Leadless Pacemaker and Atrioventricular Nodal Ablation for Atrial Fibrillation Using a Single Femoral Puncture Approach.

BACKGROUND: Atrioventricular nodal (AVN) ablation with permanent pacemaker (PPM) insertion is indicated for rate control in patients with atrial fibrillation (AF) who remain unresponsive to rate or rhythm control strategies. The leadless PPM (Micra Transcatheter Pacing System [TPS], Medtronic, Minneapolis, MN, USA) has the advantage of eliminating transvenous lead and pacemaker pocket-related complications. The aim of this case series was to determine the outcomes of patients who had undergone combined Micra TPS and AVN ablation, performed via a single femoral approach. METHOD: A retrospective review was undertaken on patients who had undergone concurrent procedures, across two major hospitals in Perth, Western Australia. Procedural details were obtained from a cardiac devices database whilst patient demographics and clinical information were determined from medical records. RESULTS: Fourteen (14) patients underwent concurrent Micra TPS insertion and AVN ablation for symptomatic AF. The average age was 73±9.2 years, and 43% of them were males. There was no acute procedural/device related complication. Over a median follow-up duration of 9 months (36% completing 12-month follow-up), there was no incidence of device complications, in particular device dislodgement, malfunction or infection. One patient had a resuscitated ventricular fibrillation (VF) arrest event with new onset cardiomyopathy during follow-up and required Micra TPS removal. One patient died at 33 days post procedure from a non-cardiac cause. Device performance was excellent with stable sensing and pacing thresholds during the follow-up period. CONCLUSION: Our study has shown that combined leadless PPM (Micra TPS) implantation and AVN ablation using a single femoral approach is feasible, with good safety and efficacy profile in the short-medium term. Long-term data involving larger cohorts is needed to confirm the findings of this study and determine the clinical usefulness of this combined approach.

Current Device Therapies for Sudden Cardiac Death Prevention - the ICD, Subcutaneous ICD and Wearable ICD.

Defibrillator technology for sudden cardiac death (SCD) prevention now includes the transvenous implantable cardiac defibrillator (ICD), subcutaneous ICD (S-ICD) and wearable cardioverter defibrillator (WCD). ICD use improves survival in patients who survived previous sudden cardiac arrest (SCA) due to ventricular tachycardia (VT)/ventricular fibrillation (VF), as well as in patients who experienced haemodynamically significant VT. It is also currently indicated for primary prevention in ischaemic/non-ischaemic cardiomyopathies, certain congenital heart disease conditions and inherited channelopathies. In this review article, we hope to present an updated review on ICD use for SCD prevention, with a focus on contemporary issues affecting ICD selection. These include: the role of primary prevention ICD in patients with non-ischaemic cardiomyopathy (NICM) in light of the 2016 DANISH (Danish Study to Assess the Efficacy of ICDs in Patients with Non-Ischemic Systolic Heart Failure on Mortality) trial; the role of defibrillator component (CRT-D) in patients receiving cardiac resynchronisation therapy (CRT-P); and the emerging role of cardiac magnetic resonance imaging (cMRI) in particular, the presence of late gadolinium enhancement (LGE), as an important SCD risk predictor. The current use of S-ICD and WCD, including clinical indications, evidence for efficacy and limitations, will also be discussed.

Dealing With the Left Atrial Appendage for Stroke Prevention: Devices and Decision-Making.

Left atrial appendage (LAA) device occlusion represents a major evolution in stroke prevention for atrial fibrillation (AF). Left atrial appendage device occlusion is now a proven strategy which provides long-term thromboembolic stroke prevention for patients with non-rheumatic AF. Evidence supports its benefit as an alternative to long-term anticoagulation while mitigating long-term bleeding risks and improving cardiovascular mortality. The therapy offers expanded options to physicians and patients negotiating stroke prevention (both primary and secondary prevention), but a good understanding of the risks and benefits is required for decision-making. This review aims to summarise the evolution of LAA device occlusion therapy, current knowledge in the field and a snapshot of current status of the therapy in clinical practice in Australia and around the world.

Characteristics of a large sample of candidates for permanent ventricular pacing included in the Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization Study (BioPace).

AIMS: The general clinical profile of European pacemaker recipients who require predominant ventricular pacing (VP) is scarcely known. We examined the demographic and clinical characteristics of the 1808 participants (out of 1833 randomized patients) of the ongoing Biventricular Pacing for Atrio-ventricular Block to Prevent Cardiac Desynchronization (BioPace) study. METHODS AND RESULTS: BioPace recruited patients between May 2003 and September 2007 predominantly in European medical centres. We analysed demographic data and described clinical characteristics and electrophysiological parameters prior to device implantation in 1808 enrolled patients. The mean age ± standard deviation (SD) of the 1808 patients was 73.5 ± 9.2 years, 1235 (68%) were men, 654 (36%) presented without structural heart disease, 547 (30%) had ischemic, 355 (20%) hypertensive, 146 (8%) valvular, and 102 (6%) non-ischemic dilated cardiomyopathy. Mean left ventricular ejection fraction was 55.4 ± 12.3%. The main pacing indications were (a) permanent and intermittent atrioventricular (AV) block in 973 (54%), (b) atrial fibrillation with slow ventricular rate in 313 (17%), and (c) miscellaneous bradyarrhythmias in 522 (29%) patients. Mean QRS duration was 118.5 ± 30.5 ms, left bundle branch block was present in 316 (17%), and atrial tachyarrhythmias in 426 (24%) patients. CONCLUSION: To the best of our knowledge, this sample is a representative source of description of the general profile of European pacemaker recipients who require predominant VP. Patients' characteristics included advanced age, predominantly male gender, preserved left ventricular systolic function, high-grade AV block, narrow QRS complex, and atrial tachyarrhythmias, the latter being present in nearly one-fourth of the cohort.

Detection of atrial high-rate events by continuous home monitoring: clinical significance in the heart failure-cardiac resynchronization therapy population.

AIMS: Uncertainty exists over the importance of device-detected short-duration atrial arrhythmias. Continuous atrial diagnostics, through home monitoring (HM) technology (BIOTRONIK, Berlin, Germany), provides a unique opportunity to assess frequency and quantity of atrial fibrillation (AF) episodes defined as atrial high-rate events (AHRE). METHODS AND RESULTS: Prospective data from 560 heart failure (HF) patients (age 67 ± 10 years, median ejection fraction 27%) patients with a cardiac resynchronization therapy (CRT) device capable of HM from two multi-centre studies were analysed. Atrial high-rate events burden was defined as the duration of mode switch in a 24-h period with atrial rates of >180 beats for at least 1% or total of 14 min per day. The primary endpoint was incidence of a thromboembolic (TE) event. Secondary endpoints were cardiovascular death, hospitalization because of AF, or worsening HF. Over a median 370-day follow-up AHRE occurred in 40% of patients with 11 (2%) patients developing TE complications and mortality rate of 4.3% (24 deaths, 16 with cardiovascular aetiology). Compared with patients without detected AHRE, patients with detected AHRE>3.8 h over a day were nine times more likely to develop TE complications (P= 0.006). The majority of patients (73%) did not show a temporal association with the detected atrial episode and their adverse event, with a mean interval of 46.7 ± 71.9 days (range 0-194) before the TE complication. CONCLUSION: In a high-risk cohort of HF patients, device-detected atrial arrhythmias are associated with an increased incidence of TE events. A cut-off point of 3.8 h over 24 h was associated with significant increase in the event rate. Routine assessment of AHRE should be considered with other data when assessing stroke risk and considering anti-coagulation initiation and should also prompt the optimization of cardioprotective HF therapy in CRT patients.

Clinical use of telemonitoring in chronic heart failure: keeping up with the times or misuse of time?

Close follow-up of patients with severe heart failure, especially after hospital discharge, has been shown to impact the mortality and readmission rates in this patient population. Monitoring of the patients' physiological status is important for predicting a potential heart failure decompensation. Earlier studies on structured telephone support and telemonitoring suggested a clear benefit on mortality and heart failure admissions, though recent large randomized controlled trials have been neutral. This review looks into the possible reasons for discrepancies in the outcomes. Remote monitoring of implantable cardiac devices is becoming increasingly utilized in a proportion of patients for device follow-up, and recent technology advances have suggested utility of certain device algorithms in detecting heart failure decompensations. Implantable hemodynamic monitors also show promise in this sphere, though have limited evidence at this stage, and further development in the technology is likely before they become part of routine practice.

Telemonitoring in chronic heart failure.

Clinical management of refractory heart failure remains challenging, with a high rate of rehospitalizations despite advances in medical and device therapy. Care can be provided in person, via telehomecare (by telephone), or telemonitoring, which involves wireless technology for remote follow-up. Telemonitoring wirelessly transmits parameters such as weight, heart rate, or blood pressure for review by health-care professionals. Cardiac implantable devices (defibrillators and cardiac resynchronization therapy) also transmit continually interrogated physiological data, such as heart rate variability or intrathoracic impedance, which may be of value to predict patients at greater risk of hospitalization for heart failure. The use of remote monitoring techniques facilitates a rapid and regular review of such data by health-care workers as part of a heart failure management programme. Current evidence supports the feasibility of such an approach but routinely assessed parameters have been shown not to impact patient outcomes. Devices that directly assess cardiac haemodynamic status through invasive measurement of pressures are currently under investigation and could potentially increase the sensitivity and specificity of predicting heart failure events. The current evidence for telemonitoring and remote monitoring, including implantable haemodynamic devices, will be reviewed.

Percutaneous extraction of a malpositioned subclavian arterial pacing lead using the retained wire technique and a vascular closure device: a case report.

Background: Inadvertent lead malposition (ILM) in the left ventricle (LV) via the subclavian artery is a rare complication during the insertion of cardiac implantable electronic devices (CIED). If not identified, there is a risk of systemic thromboembolism. Transarterial pacing lead extraction often requires surgical removal and carries high risks of bleeding and thromboembolism, but percutaneous extraction has also been previously described. Case summary: A 71-year-old female presented with left homonymous hemianopia on Day 1 post-insertion of a dual-chamber permanent pacemaker (PPM). A computed tomography (CT) angiogram of the brain and aortic arch revealed an acute occlusion of a branch of the right posterior circulating artery (PCA) and a malpositioned pacing lead in the left subclavian artery. Urgent percutaneous removal of the transarterial lead using the retained wire technique was successfully performed. Discussion: Inadvertent lead malposition in the arterial system is rare and often requires lead extraction due to systemic thromboembolic complications. The retained wire technique has been previously described for percutaneous transvenous lead extraction and exchange, but to our knowledge, we are the first to report utilizing this technique for transarterial lead extraction. Using a case report, we highlight the utility, safety, and effectiveness of the retained wire technique in extracting a malposition lead in the subclavian artery and LV.

Hybridization of long short-term memory with Sparrow Search Optimization model for water quality index prediction.

Water quality (WQ) analysis is a critical stage in water resource management and should be handled immediately in order to control pollutants that could have a negative influence on the ecosystem. The dramatic increase in population, the use of fertilizers and pesticides, and the industrial revolution have resulted in severe effects on the WQ environment. As a result, the prediction of WQ greatly helped to monitor water pollution. Accurate prediction of WQ is the foundation of managing water environments and is of high importance for protecting water environment. WQ data presents in the form of multi-variate time-sequence dataset. It is clear that the accuracy of predicting WQ will be enhanced when the multi-variate relation and time sequence dataset of WQ are fully utilized. This article presents the Water Quality Prediction utilising Sparrow Search Optimization with Hybrid Long Short-Term Memory (WQP-SSHLSTM) model. The presented WQP-SSHLSTM model intends to examine the data and classify WQ into distinct classes. To achieve this, the presented WQP-SSHLSTM model undergoes data scaling process to scale the input data into uniform format. Followed by, a hybrid long short-term memory-deep belief network (LSTM-DBN) technique is employed for the recognition and classification of WQ. Moreover, Sparrow search optimization algorithm (SSOA) is utilized as a hyperparameter optimizer of the proposed DBN-LSTM model. For demonstrating the enhanced outcomes of the presented WQP-SSHLSTM model, a sequence of experiments has been performed and the outcomes are reviewed under distinct prospects. The WQP-SSHLSTM model has achieved 99.84 percent accuracy, which is the maximum attainable. The simulation outcomes ensured the enhanced outcomes of the WQP-SSHLSTM model on recent methods.

Short-term hemodynamic effects of cardiac resynchronization therapy in patients with heart failure, a narrow QRS duration, and no dyssynchrony.

BACKGROUND: Cardiac resynchronization therapy produces both short-term hemodynamic and long-term symptomatic/mortality benefits in symptomatic heart failure patients with a QRS duration >120 ms. This is conventionally believed to be due principally to relief of dyssynchrony, although we recently showed that relief of external constraint to left ventricular filling may also play a role. In this study, we evaluated the short-term hemodynamic effects in symptomatic patients with a QRS duration <120 ms and no evidence of dyssynchrony on conventional criteria and assessed the effects on contractility and external constraint. METHODS AND RESULTS: Thirty heart failure patients (New York Heart Association class III/IV) with a left ventricular ejection fraction < or =35% who were in sinus rhythm underwent pressure-volume studies at the time of pacemaker implantation. External constraint, left ventricular stroke work, dP/dtmax, and the slope of the preload recruitable stroke work relation were measured from the end-diastolic pressure-volume relation before and during delivery of biventricular and left ventricular pacing. The following changes were observed during delivery of cardiac resynchronization therapy: Cardiac output increased by 25+/-5% (P<0.05), absolute left ventricular stroke work increased by 26+/-5% (P<0.05), the slope of the preload recruitable stroke work relation increased by 51+/-15% (P<0.05), and dP/dtmax increased by 9+/-2% (P<0.05). External constraint was present in 15 patients and was completely abolished by both biventricular and left ventricular pacing (P<0.05). CONCLUSIONS: Cardiac resynchronization therapy results in an improvement in short-term hemodynamic variables in patients with a QRS <120 ms related to both contractile improvement and relief of external constraint. These findings provide a potential physiological basis for cardiac resynchronization therapy in this patient population.

The effect of bipole tip-to-ring distance in atrial electrodes upon atrial tachyarrhythmia sensing capability in modern dual-chamber pacemakers.

INTRODUCTION: Accurate atrial arrhythmia discrimination is important for dual chamber pacemakers and defibrillators. The aim was to assess the accuracy of atrial arrhythmia recording using modern devices and relate this to atrial tip-to-ring (TTR) distance. METHODS: One hundred eighty-two patients (72 + or - 9 years, 55% male) with paroxysmal atrial fibrillation were enrolled and were included in the study if they had an atrial fibrillation (AF) burden of 1-50% during a monitoring phase. Seventy-nine patients fulfilled these criteria and were followed for at least 5 months. Electrodes were classified as having short (<10 mm), medium (10-12), or long (13-18) atrial TTR spacing. RESULTS: Two thousand eight hundred eighty-three detailed onset reports were analyzed; 730 (25%) demonstrated aberrant sensing. Six percent were due to farfield R wave oversensing (FFRWO) and 19% due to undersensing, sometimes occurring in the same patient and study phase. FFRWO was significantly reduced with short TTR electrodes (P < 0.05). Undersensing due to sensitivity fallout was 18% (short), 24% (medium), and 17% (long) (P = ns). Undersensing due to pacemaker blanking was 11% (short), 11% (medium), and 12% (long) (P = ns). Active fixation electrodes did not show any difference from passive fixation. CONCLUSION: Atrial electrodes with a short TTR (<10 mm) significantly reduce FFRWO without increasing undersensing and should be used routinely in patients with paroxysmal atrial tachyarrhythmias. However, 20% of atrial tachyarrythmia episodes were incorrectly classified as terminated by these modern devices due to undersensing. Clinicians should be wary of using device-derived endpoints that rely on AF episode number or duration as these may be falsely increased or reduced, respectively.

Toward understanding response to cardiac resynchronization therapy: left ventricular dyssynchrony is only one of multiple mechanisms.

AIM: To date, most published echocardiographic methods have assessed left ventricular (LV) dyssynchrony (DYS) alone as a predictor for response to cardiac resynchronization therapy (CRT). We hypothesized that the response is instead dictated by multiple correctable factors. METHODS AND RESULTS: A total of 161 patients (66 +/- 10 years, EF 24 +/- 6%, QRS > 120 ms) were investigated pre- and post-CRT (median of 6 months). Reduction in NYHA Class >/=1 or LV reverse remodelling (end-systolic volume reduction >/= 10%) defined response. Four different pathological mechanisms were identified. Group1: LVDYS characterized by a pre-ejection septal flash (SF) (87 patients, 54%). Elimination of SF (77 of 87 patients) resulted in reverse remodelling in 100%. Group 2: short-AV delay (21 patients, 13%) resolution (19 of 21 patients) resulted in reverse remodelling in 16 of 19. Group 3: long-AV delay (16 patients, 10%) resolution (14 of 16 patients) resulted in NYHA Class reduction >/=1 in 11 with reverse remodelling in five patients. Group 4: exaggerated LV-RV interaction (15 patients, 9%) reduced post-CRT. All responded clinically with fall in pulmonary artery pressure (P = 0.003) but did not volume respond. Group 5: patients with none of the above correctable mechanisms (22 patients, 14%). None responded to CRT. CONCLUSION: CRT response is dictated by correction of multiple independent mechanisms of which LVDYS is only one. Long-axis DYS measurements alone failed to detect 40% of responders.

Responders to cardiac resynchronization therapy with narrow or intermediate QRS complexes identified by simple echocardiographic indices of dyssynchrony: the DESIRE study.

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended for patients with NYHA class III-IV refractory heart failure (HF), ejection fraction <35% and a QRS >120 ms. We attempted to identify responders to CRT from echocardiographic (echo) indices of mechanical dyssynchrony in patients with QRS<150 ms. METHODS AND RESULTS: The study enrolled 51 men and 9 women (mean age: 64.5 years) in NYHA class III (n=54) or IV (n=6) presenting with a mean ejection fraction: 25.7%, LV end-diastolic diameter: 69.1 mm, and QRS=121+/-19 ms. All patients were implanted with a CRT system and followed for 1 year. Implantation was preceded and followed by clinical, functional and Doppler (D)-echo evaluation. The primary combined endpoint included 1) death from any cause, 2) HF-related hospitalisations, and 3) NYHA class at 6 months. Before implant, 27 patients had > or =1 echo criterion of mechanical dyssynchrony (DES+ group) and 33 had no evidence of dyssynchrony (DES- group). At 12 months, 8 patients (4 per group) had died, 7 from HF. As regards the primary endpoint at 6 months, 33 patients (55%) had improved, 10 (16%) were unchanged, and 17 (29%) had deteriorated. Clinical improvement was observed in 19 of 27 DES+ (70%), versus 14 of 33 DES- (42%) patients (P<0.04). Baseline QRS duration did not predict response to CRT. CONCLUSIONS: In this population of HF patients with QRS<150 ms, the presence of mechanical dyssynchrony at baseline D-echo examination, but not the QRS width, predicted 6-month clinical response to CRT.

NO metabolite flux across the human coronary circulation.

OBJECTIVES: The theory of a red blood cell derived nitric oxide (NO) reserve conserving NO bioactivity and delivering NO as a function of oxygen demand has been the subject of much interest. We identified the human coronary circulation as an ideal model system in which to analyse NO metabolites because of its large physiological oxygen gradient. Our objective was to identify whether oxygen drove apportion between various NO metabolite species across a single vascular bed. METHODS: Plasma and red blood cell NO metabolites were assessed from the left main coronary artery, coronary sinus and pulmonary artery (providing cross heart and cross pulmonary analysis) of healthy subjects under resting conditions and following administration of an inhibitor of NO biosynthesis. Physiological parameters and angiographic data were monitored throughout the study. RESULTS: Under baseline conditions we observed significant metabolite flux upon the transit of blood across the coronary and pulmonary vascular beds. Whilst there was no net loss of NO through the coronary circulation (p=0.0759), plasma nitrite/protein NO (excluding nitrate) (p=0.0279) and red blood cell sulphanilamide labile signal (p=0.0143) decreased whereas haemoglobin-bound NO increased three-fold (p=0.005). These changes across the coronary circulation were reversed through the pulmonary circuit with red blood cell sulphanilamide labile signal (p=0.0143) and plasma nitrite/protein NO (p=0.0279) increasing and haemoglobin-bound NO decreasing. Blockade of NO synthesis increased mean arterial blood pressure (p<0.01) and reduced coronary artery diameter (p<0.05), however we observed similar apportion of NO metabolites across the heart and lung with no net loss or gain in total NO metabolites. CONCLUSIONS: For the first time in human subjects across the resting coronary circulation we reveal significant re-apportionment of NO between metabolite species which correlate with haemoglobin oxygen saturation. These changes occur even within the transit time of blood across this single vascular bed. We demonstrate no net loss/gain of NO from the total metabolite pool across the coronary circulation even where NO biosynthesis is inhibited.

Left atrial appendage occlusion with the AMPLATZER Amulet device: one-year follow-up from the prospective global Amulet observational registry.

AIMS: Left atrial appendage occlusion (LAAO) is a stroke prevention therapy for patients with non-valvular atrial fibrillation (AF). This study reports one-year outcomes from patients enrolled in the prospective global Amulet registry. METHODS AND RESULTS: A total of 1,088 patients were recruited, aged 75±9 years; 65% of patients were male. The CHA2DS2-VASc and HAS-BLED scores were 4.2±1.6 and 3.3±1.1, respectively. Eighty-three percent (83%) of patients had contraindications to anticoagulation (OAC); 72% had a history of major bleeding. An AMPLATZER Amulet LAA occluder was successfully implanted in 99% of cases. Transoesophageal echocardiography one to three months after implant showed no residual flow or flow <3 mm in 98.4%. The observed ischaemic stroke rate was 2.9%/year. Device-related thrombus was noted in 1.7% of patients. There were ten cases between 0 and 90 days and eight cases between 91 and 365 days. Patients discharged without OAC (>80%), in particular those on single aspirin therapy, did not appear to have a higher risk of device-related thrombus. In the first year, major bleeding occurred at an annualised rate of 10.3%. All-cause mortality was 8.4% at one year. CONCLUSIONS: In the global prospective Amulet registry of patients at high risk of stroke and bleeding, the annualised ischaemic stroke rate was 2.9%. The LAA was sealed in 98.4% after one to three months and device-related thrombus was observed in 1.7% of cases with only a minority of all patients on anticoagulation treatment.

Electrical and mechanical components of dyssynchrony in heart failure patients with normal QRS duration and left bundle-branch block: impact of left and biventricular pacing.

BACKGROUND: Resynchronization pacing is an effective symptomatic treatment for heart failure patients with prolongation of the QRS duration (QRSd). Dyssynchronous contraction of the left ventricle is also observed with normal QRSd. We set out to determine how electrical activation of the left ventricular (LV) free wall differed between patients with left bundle-branch block (LBBB) and normal QRSd and if synchrony improved during pacing in patients with normal QRSd. METHODS AND RESULTS: Twenty-two patients were implanted with resynchronization pacemakers, 13 with LBBB (mean QRS, 171 ms) and 9 with normal QRSd <120 ms (mean, 100 ms). LV lead electrograms and surface ECGs in sinus rhythm (unpaced) were recorded. Conventional and tissue Doppler echocardiography were performed without pacing, with LV and biventricular pacing at optimal atrioventricular delay. Lead electrograms from the LV free wall were later in the LBBB patients in absolute terms (155 ms [SD 23] versus 65.5 ms [SD 25]; P=0.05) and also relative to the surface QRS (90.5% [SD 8] versus 65.5% [SD 24]). Improved synchrony of the left and right ventricles (interventricular synchrony) and of the LV myocardial segments (intraventricular synchrony) was observed for patients with LBBB and normal QRSd. Baseline LV synchrony correlated with timing of LV free-wall electrical activation. Improved intraventricular synchrony during pacing also correlated with LV free-wall electrical activation time. CONCLUSIONS: Resynchronization of systole can be achieved for patients with normal QRSd and LBBB during biventricular and LV pacing. The timing of LV free-wall electrical activation correlated with the improvement in synchrony.

Heart rate dependency of pulse pressure amplification and arterial stiffness.

BACKGROUND: Pulse pressure and aortic pulse wave velocity, measures of arterial stiffness, are both important determinants of cardiovascular risk. However, assessment of peripheral pulse pressure does not always provide a reliable measure of changes in central pulse pressure or arterial stiffness. The aim of the present study was to assess the effect of acute changes in heart rate on arterial stiffness and on peripheral and central pulse pressure in healthy subjects. METHODS: Twenty subjects (age range, 20 to 72 years) were studied at cardiac catheterization. Pulse wave analysis was used to determine central pressure, augmentation index (AIx), a measure of systemic arterial stiffness, and aortic pulse wave velocity (PWV) during right atrial pacing (80 to 120 beats/min). RESULTS: Pulse pressure amplification increased during pacing due to a reduction in central pressure augmentation. AIx was significantly and inversely related to heart rate (r = -0.70, P < .001) due to an alteration in the relative timing of the reflected pressure wave, rather than a reduction in arterial stiffness, as PWV did not change. CONCLUSIONS: These data suggest that peripheral pulse pressure does not provide an accurate assessment of changes in central hemodynamics in relation to changes in heart rate, and that aortic stiffness is not affected by acute changes in heart rate.

Time course and extent of collateral channel recruitment during coronary angioplasty.

OBJECTIVES: To assess the extent and timing of recruitment of collateral channels during coronary angioplasty in patients without spontaneous collaterals at diagnostic angiography. SETTING: The extent of collateral channel recruitment during coronary angioplasty is variable and its contribution to myocardial protection is not well established. The functional significance of collaterals recruited during balloon occlusion remains in question. PATIENTS: Collateral channels were assessed in 16 patients by contralateral injection at 30, 60 and 90 s into each of four 90 s inflations and by a 0.014 " Doppler guide wire distal to the lesion. RESULTS: Angiographic collateral recruitment was evident in 11 out of 16 patients (71%), but in only four (24%) by intracoronary Doppler. Grade I collaterals were present in seven patients, grade II in three and grade III in two. Collaterals were evident angiographically by 30 s in 10 out of 11 patients, with no progressive recruitment during subsequent inflations. In the four patients with Doppler evidence of collateral flow there were no differences in any flow velocity parameters with successive inflations. There was no difference in either maximum ST segment shift or time to 2 mm ST segment elevation between successive inflations. CONCLUSIONS: Collateral channel recruitment is variable between patients and appears maximal early in the first inflation. The lack of incremental recruitment of collaterals together with low or absent evidence of flow by Doppler wire suggests that these channels do not make a major contribution to myocardial protection in this setting.

Do clinical and angiographic parameters predict failure of medical therapy in patients suitable for coronary angioplasty?

AIMS: Recent studies have suggested that patients with coronary disease suitable for angioplasty have an equally good outcome with medical therapy if clinically stable. Complex lesion morphology may predict acute events without intervention and stenosis severity influences the degree of collateralisation. This study was designed to assess the influence of these factors on clinical outcome. METHODS AND RESULTS: A retrospective review of patients suitable for angioplasty who were randomised to initial medical therapy as part of a multicentre study. Angiograms were reviewed for lesion characteristics, TIMI flow grade, and degree of collateralisation. Angiograms were available on 79 patients (13 female, 66 male). Mean age was 54.8 years (range 43-68) in the group crossing-over to revascularisation, and 58.4 (range 37-78) in the group who did not (P=ns). Seventeen patients crossed-over (two to CABG, 15 to PTCA) at 5.4 months (range 0-10) after initial angiography. Disease progression had occurred in 10/17 patients (58.8%), three of whom developed a new occlusion. Collateralisation was more likely in smokers, independent of lesion severity (P<0.05). Time to cross-over was not influenced by progression of disease. Crossing-over was not affected by age, diabetic status, cholesterol level, vessel involved, lesion severity, TIMI flow, lesion morphology, collateralisation, or the number of vessels diseased, but was more likely in females (P<0.05). CONCLUSION: This group of patients generally does well with medical therapy. Whilst the numbers are relatively small, there does not appear to be any reliable prospective marker, including the presence of spontaneous collateral channels on diagnostic angiography, to indicate which patients will fail medical therapy and require revascularisation.