Search

Peer reviewed: True, Funder: National School of Healthcare Science, Background: Patients with implantable cardioverter defibrillators (ICD) experience anxiety, depression and reduced quality of life (QoL). Objectives: This mixed-methods systematic review evaluates whether ICD support groups have a beneficial effect on mental well-being. Methods: Literature searches were carried out in MEDLINE, Embase, CINAHL, PsycINFO and Web of Science. Eligible studies investigated patient-led support groups for ICD patients aged 18 years or older, using any quantitative or qualitative design. The Mixed-Methods Assessment Tool was used to assess quality. Meta-analysis of measures of mental well-being was conducted. Thematic synthesis was used to generate analytic themes from the qualitative data. The data were integrated and presented using the Pillar Integration Process. Results: Ten studies were included in this review. All studies bar one were non-randomised or had a qualitative design and patients had self-selected to attend a support group. Five contributed to the quantitative data synthesis and seven to the qualitative synthesis. Meta-analysis of anxiety and QoL measures showed no significant impact of support groups on mental well-being, but qualitative data showed that patients perceived benefit from attendance through sharing experiences and acceptance of life with an ICD. Discussion: ICD support group attendance improved the patients’ perceived well-being. Attendees value the opportunity to share their experiences which helps to accept their new life with an ICD. Future research could consider outcomes such as patient acceptance and the role of healthcare professionals at support groups.

Introduction Hospital admissions of patients with cardiovascular disease were markedly reduced in the UK in 2020 during the Covid-19 pandemic. In many institutions, including ours, patient care was redistributed from a specialty-based approach to a ward-based system, meaning some patients being admitted and managed under the care of non-specialist teams. Purpose We wished to examine the impact of these changes on heart failure (HF) patients presenting during the pandemic and on appropriate delivery of complex device therapies. Methods The study was undertaken in a large UK teaching hospital. The institution audit programme includes cardiac device therapy provision, aiming to ensure that implantable cardioverter defibrillators and cardiac resynchronisation therapy are offered to the target population in accordance with NICE guidance [Technology Appraisal 314]. In accordance with the guidance, patients admitted to hospital with serious ventricular arrhythmia, familial cardiac condition with high risk of sudden cardiac death (SCD), surgical repair of congenital heart disease (CHD) and patients with HF and LVEF Results Among non-HF patients, device therapy prescription was consistent in the two periods observed. Table 1 shows how many patients were eligible for device therapy and how many were offered it. Table 2 contains details of HF admissions, showing an 8% reduction in admissions during the pandemic. The proportion of patients eligible for device therapy did not change significantly. However, there was a significant reduction in the proportion of eligible patients who were offered device therapy (79% vs 94% p=0.03). In addition, during the pandemic there was a trend towards a greater chance of patients being considered too frail for device therapy (p=0.08). Among 12 patients overlooked for device therapy, 10 were not under the care of Cardiology. Among 31 patients considered too frail for device therapy, 26 were not under the care of Cardiology. Conclusion During the Covid-19 pandemic, a modest reduction in HF hospital admission was observed with a marked fall in identification of patients eligible for device therapy. Possible explanations include intense pressure to discharge patients quickly, an increased perception of patient frailty during a crisis and the lack of recognition of indications for device therapy when patients are under the care of non-specialists. These findings suggest that cardiac services should actively look for HF patients who may have missed out on life-saving device therapies during the pandemic. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Superior response to CRT and improved clinical outcomes can be achieved when placing the left ventricular (LV) lead at the site of latest mechanical activation and avoiding regions of scar during cardiac resynchronisation therapy (CRT). The site of latest mechanical activation can be identified using speckle-tracking echocardiography according to the TARGET study, whilst the area of latest electrical activation can be assessed by measuring the intrinsic LV electric delay (QLV), which is the time from the initial deflection of the surface QRS complex to sensing at the LV lead electrode. It remains unclear if the two techniques are interchangeable and whether the site of latest mechanical activation is related to the site of latest electrical activation, or whether sensed electrical signals correspond to sites of scar.Purpose: The purpose of this study was to determine whether electrical targeting of LV lead position corresponds to echo-guided mechanical targeting and whether myocardial electrogram signals can predict areas of myocardial scar Methods This was a pilot study of patients receiving CRT, in sinus rhythm with severe LV impairment (ejection fraction ≤35%) and left bundle branch block (LBBB) with QRS ≥130ms. Ethics approval was obtained, and written consent was sought. Participants underwent echocardiographic speckle-tracking 2-dimensional radial strain imaging to identify amplitude and time to peak contraction of posterior, posterolateral, lateral, anterolateral and anterior segments. During CRT implant, the sensed R wave and QLV were measured at the respective branch of the coronary sinus, where the anatomy permitted. The site of latest mechanical was compared to the site of latest electrical activation and classified as concordant (same site), adjacent (within 1 segment), or remote (2 segments away). The strain amplitude was compared to the sensed R wave and time to mechanical activation with QLV. Results Seventeen patients (13 male) were studied, mean age 74.2 (SD 8.7). Mean QRS was 161 ms (SD 18), mean PR 186 ms (SD 37). A modest and significant positive correlation was found between the site of latest mechanical and latest electrical activation (Pearson r=0.66, p 0.004). The site of latest electrical activation was concordant with latest mechanical activation in 13 patients (76.5%), adjacent in 4 patients (23.5%) and remote in none. There was no apparent association between sensed R wave and strain amplitude (Pearson r=0.2, p=0.12) or between QLV and time to mechanical activation (Pearson r=0.1, p=0.5). Conclusion A significant positive correlation was found between the site of latest mechanical and latest electrical activation in patients undergoing CRT implant. Electrical targeting might be a suitable alternative to mechanical targeting particularly when imaging is not available, however, does not appear to discriminate scar. Future larger studies are needed to confirm our findings and determine whether QLV can be used as an alternative method for targeting LV lead placement. Conflict of Interest None

Introduction The 2020 Covid-19 pandemic saw a marked nationwide reduction in hospital admissions due to cardiovascular disease. In many institutions, including ours, it also saw redistribution of patient care from a specialty-based approach to a ward-based system, meaning patients being admitted and remaining under the care of non-specialist teams. We wished to examine the impact of these changes on heart failure patients presenting during the pandemic and on appropriate delivery of complex device therapies. Methods The study was undertaken in a large UK teaching hospital, where the annual audit programme includes NICE guidance (Technology Appraisal 314: Implantable Cardioverter Defibrillators and Cardiac Resynchronisation Therapy for Arrhythmias and Heart Failure). As per the NICE guideline, patients admitted to hospital were identified, using discharge codes, with: serious ventricular arrhythmia;familial cardiac condition with high risk of sudden cardiac death (SCD);surgical repair of congenital heart disease;and patients with heart failure and LVEF

Introduction The Covid-19 pandemic has put a considerable strain on procedural waiting lists, with the majority of elective outpatient work cancelled during the pandemic. With the vaccination programme and reducing infection levels, attention is turning to addressing these waiting lists. One procedure that was affected was the removal of implantable loop recorders (ILRs). Manufacturers recommend that ILRs are removed at the point of battery depletion (usually 3-4 years), if they have not already been removed due to a positive finding or patient preference. There is little evidence in the literature regarding late complications with ILRs, and we therefore wished to examine what patients’ thoughts would be about keeping the ILR in for a longer period of time. Methods Patients awaiting ILR explantation and those who had undergone explantation, were identified. A retrospective review of the notes was used to get demographic and clinical data. Both groups of patients were contacted, and a questionnaire used to gain an understanding of patients’ experience and expectations. Results Prior to the Covid-19 pandemic, 60 patients who had undergone ILR explantation were identified. A total of 22 responded to our questionnaire (table 1). The majority (86%) were happy to have their ILR removed, although a smaller majority (59%) would also have been happy to have had the device kept in, were it felt to be safe. Very few patients felt a tangible difference as a result of having the ILR removed (14%) and no patients were worried about the waiting time prior to Covid-19. Of 77 patients currently awaiting explant, 30 responded to our questionnaire (table 1), with 70% not being concerned by the wait for removal. This is likely aided by the fact that 80% of patients had no day to day symptoms as a result of the ILR. Half of the patients however, would be concerned about not having the ILR removed, predominantly due to mild discomfort or concerns regarding the presence of a battery. Across both groups (n=52) only 8 patients were concerned about the risk of coming into the hospital for the procedure, with patients commenting that the stringent regulations that hospitals had employed combined with the vaccination programme, gave them significant confidence in attending for outpatient procedures. Conclusions This study found that if patients are reassured about the safety of keeping an implantable loop recorder in, and do not suffer any discomfort or symptoms as a result of the device, they are happy both to wait longer for device removal, or even not have it removed at all. In the context of the current pandemic, more thought should perhaps be given to patient guided removal times, especially in cases of removals performed for battery depletion. Conflict of Interest Nil

Introduction The implantable cardioverter defibrillator (ICD) is an important treatment option for heart failure patients, protecting against sudden cardiac death. Current guidelines highlight left ventricular (LV) systolic function as the principal measure, for most patients, used to decide which patients receive ICD implantation. Referral for ICD implant is dependent upon recognition of the indication by the patient’s physician. It is also recognised that sudden death risk is not solely a function of LV systolic function and guidelines could potentially exclude patients at risk of sudden death. We wished to ascertain how many patients presenting with life-threatening ventricular arrhythmias were already known to have an indication for ICD therapy, how many fell outside of current guidelines for primary prevention and, among the latter, what the underlying cardiac diagnoses were. Methods In a 5-year single-centre retrospective study within a large teaching hospital, we used the hospital electronic patient record to identify patients admitted with new presentation of ventricular arrhythmia, who did not have an ICD in-situ. Case-notes were reviewed to identify whether patients already had a known indication for ICD implant and to determine the cardiac background. Results Of 779 inpatient admissions with a code for ventricular arrhythmia, 302 patients were found to have had life-threatening arrhythmia. Of these, 79 had already received ICD implant. The clinical status of the remaining 223 patients is shown in Table 1. After excluding patients with acute provocation (68) and 21 patients with severe LV impairment deemed ineligible for ICD therapy, 128 surviving patients were considered eligible to receive ICD implantation. Among these, 23 patients (18%) had a previously known guideline-based indication for primary prevention ICD treatment, of whom 10 died without leaving hospital (43.5%). 53 patients (41%) had structural heart disease not meeting criteria for primary prevention ICD (Table 2). Conclusions Nearly one fifth of patients presenting to hospital with life-threatening ventricular arrhythmia and eligible for ICD therapy already had an identified indication for primary prevention ICD that had gone unrecognised, leading to potentially avoidable deaths. Two fifths of patients had cardiac disease falling outside of primary prevention guideline criteria. More widespread understanding of guidelines for recommending ICD therapy is important for ensuring that this treatment is offered to all eligible patients. This study suggests that current guidelines are unsatisfactory in identifying a substantial proportion of patients who may benefit from primary prevention ICD implantation. Conflict of Interest none

Learning objectives Cardiac resynchronisation therapy (CRT) is a well-established treatment for heart failure (HF). The Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure1 and Cardiac Resynchronisation Heart Failure (CARE-HF)2 trials found that CRT reduces both morbidity and mortality in HF patients. Based on current guidelines, 6%–12% of patients hospitalised with HF are eligible for CRT.3 CRT helps to restore atrioventricular (AV), interventricular (VV) and intraventricular synchrony, improve left ventricular (LV) function, reduce functional mitral regurgitation and induce LV reverse remodelling, as evidenced by increases in LV filling time and left ventricular ejection fraction (LVEF), and decreases in LV end-diastolic and end-systolic volumes, mitral regurgitation and septal dyskinesis.2 4 Up to 30% of patients receiving CRT do not attain symptomatic benefit.5 Various parameters have been used to define response to CRT, including improvement in New York Heart Association (NYHA) functional class, improvement in quality of life and echocardiographic parameters. There are five different possible clinical outcomes post-CRT implantation. Responders (70%) show a measurable improvement, whereas super-responders (5%) show excellent response up to normalisation of LV function. Non-progressors (10%) do not experience the progressive decline that is observed in non-responders (10%), and negative responders (5%) experience clinical deterioration and decline in LV function.6 7 Given the inherent risks and costs of device implantation and maintenance, a reduction in the rate of lack of response to CRT is an important goal. Factors associated with a lack of response include inappropriate patient selection, suboptimal LV lead placement, presence of myocardial scar, inadequate device programming and failure to deliver continuous biventricular (BiV) pacing.5 …

Preclinical data have shown that rilmenidine can regulate autophagy in models of Huntington’s disease (HD), providing a potential route to alter the disease course in patients. Consequently, a 2-year open-label study examining the tolerability and feasibility of rilmenidine in mild-moderate HD was undertaken. 18 non-demented patients with mild to moderate HD took daily doses of 1 mg Rilmenidine for 6 months and 2 mg for a further 18 months followed by a 3-month washout period. The primary outcome was the number of withdrawals and serious adverse events. Secondary outcomes included safety parameters and changes in disease-specific variables, such as motor, cognitive and functional performance, structural MRI and serum metabolomic analysis. 12 patients completed the study; reasons for withdrawal included problems tolerating study procedures (MRI, and venepuncture), depression requiring hospital admission and logistical reasons. Three serious adverse events were recorded, including hospitalisation for depression, but none were thought to be drug-related. Changes in secondary outcomes were analysed as the annual rate of change in the study group. The overall change was comparable to changes seen in recent large observational studies in HD patients, though direct statistical comparisons to these studies were not made. Chronic oral administration of rilmenidine is feasible and well-tolerated and future, larger, placebo-controlled, studies in HD are warranted. Trial registration: EudraCT number 2009-018119-14. Electronic supplementary material The online version of this article (doi:10.1007/s00415-017-8647-0) contains supplementary material, which is available to authorized users.

A substantial proportion of patients who undergo cardiac device implantation receive oral anticoagulation to prevent thromboembolism or antiplatelets to prevent thrombotic events. Anticoagulation and antiplatelets increase the risk of hemorrhagic complications, while discontinuation may increase thromboembolic risk and thrombotic events. With the introduction of non-vitamin K antagonist oral anticoagulant agents and the newer antiplatelet agents such as prasugrel or ticagrelor, the perioperative management of patients has become more challenging. In this article, we review the recent trials and meta-analysis and describe the available evidence, as well as the current recommendations in order to inform best practice. We also reinforce the importance of further trials in this complex and rapidly evolving area.

Aims 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. Methods and results Data were analysed from 294 patients undergoing CRT between June 2008 and December 2012. All patients were in sinus rhythm with QRS >120 ms, NYHA class II–IV, and LVEF 150 ms and non-ischaemic aetiology. A cut-off score 3.28 offered high specificity (specificity 86%, sensitivity 70%) to predict response. Survival proportion at longer term follow-up was low (21%) in the group with predictive score

Objectives This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT). Background An 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. Methods Data 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. Results An 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 Conclusions An 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.

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 [RSD c ]), 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%). RSD c 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), RSD c was higher in responders compared with nonresponders (74±39% versus 29±15%; P r =−0.53; P c >40% predicted remodeling (sensitivity, 87%; specificity, 88%). In the validation group (n=108), RSD c similarly predicted response (sensitivity, 89%; specificity, 84%). Survival at long-term follow-up was greater in patients with RSD c >40% ( P Conclusions— RSD c , based on both the timing and the amplitude of segmental strain, has a strong predictive value for CRT remodeling response and long-term survival.

Objectives This study sought to assess the impact of targeted left ventricular (LV) lead placement on outcomes of cardiac resynchronization therapy (CRT). Background Placement of the LV lead to the latest sites of contraction and away from the scar confers the best response to CRT. We conducted a randomized, controlled trial to compare a targeted approach to LV lead placement with usual care. Methods A total of 220 patients scheduled for CRT underwent baseline echocardiographic speckle-tracking 2-dimensional radial strain imaging and were then randomized 1:1 into 2 groups. In group 1 (TARGET [Targeted Left Ventricular Lead Placement toGuide Cardiac Resynchronization Therapy]), the LV lead was positioned at the latest site of peak contraction with an amplitude of >10% to signify freedom from scar. In group 2 (control) patients underwent standard unguided CRT. Patients were classified by the relationship of the LV lead to the optimal site as concordant (at optimal site), adjacent (within 1 segment), or remote (≥2 segments away). The primary endpoint was a ≥15% reduction in LV end-systolic volume at 6 months. Secondary endpoints were clinical response (≥1 improvement in New York Heart Association functional class), all-cause mortality, and combined all-cause mortality and heart failure–related hospitalization. Results The groups were balanced at randomization. In the TARGET group, there was a greater proportion of responders at 6 months (70% vs. 55%, p = 0.031), giving an absolute difference in the primary endpoint of 15% (95% confidence interval: 2% to 28%). Compared with controls, TARGET patients had a higher clinical response (83% vs. 65%, p = 0.003) and lower rates of the combined endpoint (log-rank test, p = 0.031). Conclusions Compared with standard CRT treatment, the use of speckle-tracking echocardiography to the target LV lead placement yields significantly improved response and clinical status and lower rates of combined death and heart failure–related hospitalization. (Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy [TARGET] study); ISRCTN19717943 )

The increasing use of implantable electronic devices such as cardiac pacemakers and neurostimulators means that they are being increasingly encountered in endoscopy departments. The electromagnetic fields generated during electrosurgery and with magnetic imaging systems have the potential to interfere with such devices. The authors present a case that highlights some of the steps necessary for minimising risk, review the evidence and summarise the currently available guidance.

Aims: Noninvasive 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. Methods: Two hundred and three patients undergoing CRT were assessed in two consecutive nonrandomized groups; an empiric group (n = 54) was programmed to “out of the box” settings with a fixed AV delay of 120 ms and a VV delay of 0 ms; and the optimization group (n = 149) underwent adjustments of both the AV and VV delays according to the greatest improvement in resting CO. The primary endpoints were improvements in left ventricular (LV) volumes and function from baseline at 6 months. Secondary endpoints were change in New York Heart Association (NYHA) class, quality of life score, and 6-minute walk test (6 MWT) performance. Results: After 6 months of CRT, the optimization group had a better clinical response with lower NYHA class (2.1±0.8 vs 2.4 ± 0.8, P = 0.048) and quality of life scores (35 ± 18 vs 42 ± 20, P = 0.045) but no differences in 6-MWT performance (269 ± 110 vs 277 ± 114 m, P = 0.81). Echocardiographic response was also better in the optimization group with lower LV end systolic volume (108 ± 51 vs 126 ± 60 mL, P = 0.048) and higher ejection fraction (30 ± 7 vs 27 ± 8, P = 0.01) compared to empiric settings. Conclusion: Device optimization using noninvasive measures of CO is associated with better clinical and echocardiographic response compared to empiric settings. (PACE 2011; 34:1527–1536)

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.

Aims Left 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. Methods and results In 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). Conclusion VV optimization overcomes some but not all of the deleterious effects of a suboptimal LV lead position.

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. Methods: In 131 CRT patients, the LV lead was positioned preferentially in a lateral or posterolateral vein and the RV lead to either the RV septum (RVS, n = 55) or RV apex (RVA, n = 76). The latest site of contraction was determined with two-dimensional speckle tracking radial strain imaging and patients had a concordant LV lead position if pacing the latest segment, and discordant if not. Response was defined as ≥15% reduction in LV end systolic volume (LVESV) at 6-month follow-up. Results: There were no significant differences in mean reduction of LVESV at follow-up (RVS vs RVA: −23.3 ± 16% vs 22.1 ± 18%, P = 0.70) or rate of responders (58.2% vs 57.9%, P = 0.97) between the two groups. In patients with a concordant LV lead (n = 71), the response rate was significantly higher than those with a discordant lead (76.1% vs 36.7%, P < 0.001). There were no differences in outcomes in patients with a concordant or discordant LV lead according to the RV lead location. Conclusion: The extent of LV reverse remodeling following CRT is not related to the RV lead position, but is significantly higher in patients with a concordant LV lead. (PACE 2011; 34:467–474)

Background To examine the effect of serum testosterone levels on survival in a consecutive series of men with confirmed coronary disease and calculate the prevalence of testosterone deficiency. Design Longitudinal follow-up study. Setting Tertiary referral cardiothoracic centre. Patients 930 consecutive men with coronary disease referred for diagnostic angiography recruited between June 2000 and June 2002 and followed up for a mean of 6.962.1 years. Outcome All-cause mortality and vascular mortality. Prevalence of testosterone deficiency. Results The overall prevalence of biochemical testosterone deficiency in the coronary disease cohort using bio-available testosterone (bio-T)

Heart failure is posing an increasing burden on healthcare systems around the world, a consequence of increased survival from acute coronary syndromes and life-prolonging medications. Cardiac resynchronization therapy has become a ratified and established therapy for heart failure to reduce both the morbidity and mortality of the condition. Its prophylactic role in patients who have minimal symptoms to delay future deterioration is a novel development. The indications for this therapy continue to evolve, mainly as a result of company-sponsored multicenter trial data aimed at broadening its usage. Uncertainty remains on how to accurately identify individuals who will respond to resynchronization therapy and how best to manage patients following device implant.

Non-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.Forty-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) by15%. 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, P0.001). A 20% increase in acute CO following CRT predicted LVESV reduction of15% 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, P0.01) and for VV delay in 39 of 47 patients (83%, r = 0.89, P0.01).Non-invasive cardiac output monitoring is a simple, reliable, and portable alternative to echocardiography to program CRT devices.

Evaluation of: Pocock SJ, McMurray JJV, Dobson J et al. Weight loss and mortality risk in patients with chronic heart failure in the Candesartan in Heart failure: Assessment of Reduction in Mortality and morbidity (CHARM) programme. Eur. Heart J. 29, 2641-2650 (2008). Among patients with heart failure, the usual association between obesity and reduced survival appears to be turned on its head. Increasing numbers of studies appear to confirm the apparent protective effect of the 'obesity paradox' in heart failure. The adverse effects of weight loss and cachexia have been recognized among patients with chronic disease. The paper under evaluation clarifies and offers further insight into the impact of BMI and weight loss on prognosis in a large sample of heart failure patients. The results confirm and extend previous knowledge. They raise many questions, not only regarding the underlying pathophysiology that leads to this counterintuitive relationship observed in the obese heart failure group, but also as to how we should best approach and advise these patients on weight management in day-to-day practice.

Evaluation of: Jankowska EA, Biel B, Majda J et al. : Anabolic deficiency in men with chronic heart failure; prevalence and detrimental impact on survival. Circulation 114, 1829–1837 (2006). The study examined the circulating levels of three anabolic hormones (testosterone, insulin-like growth factor-1 and dehydroepiandrosterone sulfate) in 208 men with stable chronic heart failure and 366 healthy controls. A high prevalence of anabolic hormone deficiency (89% deficient in one or more hormone) was found in heart failure patients. Hormone levels were weakly related to disease severity and hormone deficiency independently predicted prognosis (a 3-year survival rate of 27% was found in subjects deficient in all three hormones). Although it cannot be concluded that anabolic hormone deficiency contributes to the disease process – it may simply reflect chronic disease with no physiological consequence – it is highly plausible that deficiency may at least contribute to symptomatology. Further studies evaluating anabolic hormone replacement for symptomatic improvement and possible prognostic benefit are warranted.

A substantial proportion of patients who undergo cardiac rhythm device implantation receive anticoagulation to prevent thromboembolism. Many patients have coexisting cardiovascular diseases treated with antiplatelet therapy. Anticoagulation may increase the risk of hemorrhagic complication, while withdrawal of anticoagulation may increase thromboembolic risk. In this article, we review and describe the available evidence, in order to inform best practice.

Testosterone has classically been considered to exert a detrimental influence upon the cardiovascular system due to the high male prevalence of coronary artery disease (CAD), which even after correcting for sex-dependent differences in risk factors, remains double that in women (Wingard et al., 1983; Jousilahti et al., 1999). However, numerous cross-sectional case control studies report hypotestosteronaemia in patients with heart disease (reviewed in Alexandersen et al. (1996)) and a recent study by our group has demonstrated that men with significant CAD have markedly reduced circulating levels of testosterone (English et al., 2000c). Similarly, testosterone levels are reported to be inversely proportional to atherosclerotic risk (Khaw & Barrett-Connor, 1991; Duell & Bierman, 1990; Hromadova et al., 1991), and other risk factors for CAD including hypertension, hyperinsulinaemia, diabetes, obesity, smoking, age and an adverse thrombotic profile are all associated with hypotestosteronaemia (reviewed in English et al., 1997). Such observations contradict this traditional view and suggest that testosterone is beneficial to the cardiovascular system, at least in male individuals, and that it is a relative deficiency in circulating testosterone which is associated with coronary heart disease. Indeed, a number of studies support this hypothesis. Research dating back to the 1940s has demonstrated a beneficial effect of testosterone therapy in male patients with angina (Hamm, 1942; Walker, 1942; Sigler & Tulgan, 1943; Lesser, 1946), although it was a further 30 years until the first placebo-controlled data was provided: Jaffe (1977) reported an improvement in myocardial ischaemia in men who had received either four or eight, weekly intramuscular testosterone injections. Subsequent studies have demonstrated that chronic administration of high dose oral testosterone (Wu & Weng, 1993), and physiological trans-dermal testosterone (English et al., 2000d), also improve symptom scores of angina and reduce objective measures of myocardial ischaemia. Furthermore, acute administration of testosterone also provides rapid improvements in myocardial ischaemia (Webb et al., 1999a; Rosano et al., 1999), prompting the suggestion that testosterone may beneficially influence coronary vascular tone. Indeed, in subsequent studies Webb et al. (1999b) demonstrated that an intra-coronary infusion of physiological concentrations of testosterone increased coronary artery diameter and coronary blood flow in male patients with CAD, consistent with a direct coronary vasodilatory action. Numerous animal studies have also demonstrated that testosterone acts as a direct coronary vasodilator in a variety of species, including rabbit, dog, pig and rat, both in vivo (Chou et al., 1996) and in vitro (Yue et al., 1995; Murphy & Khalil, 1999; Crews & Khalil, 1999a; English et al., 2000b; 2002; Deenadayalu et al., 2001). The beneficial effects of testosterone upon myocardial ischaemia are attributed to this activity. Testosterone is also reported to exhibit a vasodilatory action in thoracic aortae (Yue et al., 1995; Perusquia et al., 1996; Honda et al., 1999; Ding & Stallone, 2001) and in vessels isolated from the mesenteric (Tep-Areenan et al., 2002) and pulmonary (English et al., 2001; Jones et al., 2002a) vasculature. Furthermore, recent reports demonstrate that both acute administration of intravenous testosterone (Ong et al., 2000) and chronic administration of oral testosterone (Kang et al., 2002) enhance brachial artery responsiveness to flow and nitrate-mediated dilatation in men with CAD. Such observations demonstrate that in addition to a direct vasodilatory action, testosterone also exerts a beneficial effect upon the regulation of vascular tone controlled by the release of nitric oxide from the endothelium, and in the clinical setting in which such therapy could be employed – male patients with significant CAD.

Heart failure has traditionally been considered a disease of the myocardium, with symptoms arising from altered haemodynamics. However, it is now recognised that, in addition to marked neuroendocrine disturbance, there is perturbation of cytokine expression in patients with heart failure, resulting in an inflammatory imbalance. This not only influences symptoms, but also plays a central role in the underlying pathophysiological processes of heart failure, leading to disease progression and poorer prognosis. Recognition of the influence of cytokines, in particular tumour necrosis factor, has opened a new avenue for potential therapies for heart failure. Current approaches involve immunomodulation, aimed at suppressing tumour necrosis factor. We suggest that androgens may potentially offer a superior therapeutic strategy by their well-recognised non-specific immunosuppressive and anti-inflammatory effects. Studies of cell lines, human mononuclear cells and animals in vivo have demonstrated the 'anti-cytokine' actions of androgens, and we have found a similar action in whole blood from patients with heart failure. These effects, along with the anabolic action of these agents, make androgens an attractive potential option for treatment of patients with heart failure.

Recent evidence supports a beneficial effect of testosterone on the cardiovascular system. Testosterone acts as a coronary vasodilator and reduces myocardial ischemia in men with coronary heart disease. The aim of the current study was to determine whether testosterone has a similar vasodilatory action in the pulmonary circulation and to characterize the underlying mechanism of action. The vasodilatory action of testosterone was studied in pulmonary arteries (n = 132, mean internal diameter = 344 +/- 8 microm) isolated from male rats (n = 48, mass = 396 +/- 7 g) mounted in a small vessel wire myograph and loaded to a tension equivalent to 17.5 mm Hg. Micromolar concentrations of testosterone induced dilatation in pulmonary arteries preconstricted with prostaglandin F2alpha (100 microM) within seconds of application. Dilatation to testosterone was similar in vessels treated with N-gamma-nitro-l-arginine methyl ester (l-NAME) (10 microM) or vehicle (5 microl distilled water), -38.2 +/- 2.9%, and -38.1 +/- 3.4%, respectively, and in vessels treated with indomethacin (10 microM), flutamide (10 microM), or vehicle (5 microl ethanol), -35.5 +/- 2.8%, -43.2 +/- 3.6%, and -35.7 +/- 4.6%, respectively (all p > 0.05). Maximal dilatation to testosterone occurred following preconstriction with agents that activated voltage-gated calcium channels such as prostaglandin F2alpha (-34.6 +/- 5.0%), BAY K8644 (-32.9 +/- 8.7), or potassium chloride (-26.7 +/- 1.5%), compared with calcium-independent protein kinase C activation by phorbol dibutyrate (-14.7 +/- 1.6%) or capacitative calcium entry via thapsigargin (-5.1 +/- 0.9%). This study demonstrates that testosterone induces pulmonary dilatation via a mechanism that is independent of the classic androgen receptor and also of the release of nitric oxide or dilator prostaglandins. The data support a calcium antagonistic action for testosterone in the pulmonary circulation, primarily against voltage-gated calcium channels.

The effect of acute myocardial infarction on plasma levels of testosterone in men is unclear. No previous studies have evaluated the bio-available fraction of testosterone. Low plasma testosterone levels have been associated with several risk factors for myocardial infarction, including an unfavorable fibrinolytic profile. In a prospective, case control study, we examined changes in plasma levels of sex hormones, including bio-available testosterone, in patients with acute myocardial infarction and in control subjects. In addition, changes in hormone levels in patients were compared with alterations in the fibrinolytic profile. Thirty male patients admitted with chest pain were studied. Twenty two had acute myocardial infarction and eight had non-specific chest pain. Plasma levels of total and bio-available testosterone, 17beta-estradiol, sex hormone binding globulin and insulin were measured at baseline and throughout admission. In addition, fibrinolytic factors (plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) and fibrinogen) were measured in patients who received fibrinolysis. Height and weight, and the subsequent development of heart failure or myocardial dysfunction were also recorded. Patients had lower levels of bio-available testosterone (2.07 +/- 0.75 nmol/L vs. 5.3 +/- 1.7 nmol/L, p < 0.05) and higher levels of 17beta-estradiol (87.9 +/- 39.5 pmol/L vs. 48.1 +/- 18.4 pmol/L, p < 0.001) than controls. Total and bio-available testosterone levels fell acutely following myocardial infarction (11.9 +/- 3.8 nmol/L to 9.7 +/- 3.3 nmol/L, p < 0.05; 1.95 +/- 0.76 nmol/L to 1.55 +/- 0.67 nmol/L, p < 0.05). This reduction was associated with elevation of PAI-I activity and reduction of tPA activity, independent of changes in plasma insulin levels. Patients with lower baseline levels of testosterone and higher levels of 17beta-estradiol had a relatively pro-thrombotic fibrinolytic profile and increased risk of complications. In conclusion, total and bio-available levels of testosterone fall following acute myocardial infarction in men, in association with adverse changes in fibrinolytic profile. It is not clear whether this association represents a direct effect of testosterone on thrombotic tendency but warrants further investigation.

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.Data were analysed from 294 patients undergoing CRT between June 2008 and December 2012. All patients were in sinus rhythm with QRS120 ms, NYHA class II-IV, and LVEF35%. Detailed clinical assessment including echocardiography was completed at baseline and 6 months after CRT. Response was defined as a ≥15% reduction in LV end-systolic volume. Dyssynchrony (interventricular delay and radial strain delay), global longitudinal strain, and LV lead position were independent predictors of LV remodelling and were used to derive a predictive score which correlated with reduction in LV volume (r = - 0.5, P0.001) and was higher with QRS150 ms and non-ischaemic aetiology. A cut-off score0.6 offered the highest specificity and positive predictive value (100%) to determine non-response. A score3.28 offered high specificity (specificity 86%, sensitivity 70%) to predict response. Survival proportion at longer term follow-up was low (21%) in the group with predictive score0.6.A multiparametric strategy, which defines anticipated probability of response to CRT, offers potential to predict non-responders with poor long-term survival following CRT. The value of this approach in avoiding unnecessary device implantation with potential for harm requires validation in large multicentre studies.

Background and study aims: Use of the colonoscope magnetic imaging device (ScopeGuide, Olympus Medical Systems, Tokyo, Japan) is currently contraindicated by the manufacturer for patients with implantable cardiac devices, a group of patients that is increasing annually along with the number of colonoscopies performed in the era of colorectal cancer screening. This is the first study to examine the safety of ScopeGuide in patients with permanent pacemakers, implantable cardioverter defibrillators, and cardiac resynchronization therapy. Patients and methods: Nonimplanted cardiac devices were exposed to the electromagnetic field of ScopeGuide ex vivo and assessed for evidence of interference or change in device settings. Following this, consecutive patients attending device check clinics were prospectively recruited and exposed to the ScopeGuide electromagnetic field. After an initial device check, patients underwent continuous external cardiac monitoring and device interrogation while a colonoscope was placed on the abdomen over clothing and connected to ScopeGuide to simulate colonoscopy. Patients were monitored for 2 minutes to assess for any interference. ScopeGuide was then disconnected and devices were checked for any change in settings. Results: A total of 230 patients were invited to participate and 100 were recruited to the study. There was no evidence of interference on device leads or change in programming following exposure to the electromagnetic field generated by ScopeGuide. Conclusion: ScopeGuide does not appear to cause interference or change in settings and is therefore likely to be safe for use in patients with implantable cardiac devices.

Chronic congestive heart failure (CHF) remains a significant cause of mortality and morbidity in the UK, accounting for 5% of acute hospital admissions and 1% of the total NHS budget.1 Coronary artery disease (CAD) and hypertension are the most commonly associated conditions. The condition is characterized by left ventricular dysfunction, impaired vascular tone and skeletal muscle abnormalities, producing breathlessness and fatigue. Neuro‐hormonal and cytokine activation are self‐perpetuating maladaptive responses to the failing heart, which cause further deterioration in cardiac function and increased catabolism. The mainstay of current therapy includes diuretics and neuro‐hormonal manipulation; ACE inhibitors are well established as the most important intervention for improving prognosis, and angiotensin II receptor antagonists offer a good alternative.2 More recently, reduced mortality has been demonstrated from the use of both beta‐blockers and the aldosterone receptor antagonist spironolactone.3,,4 Vasodilators may also provide symptomatic and prognostic benefit. However, the only therapy offering long‐term survival is cardiac transplantation, which remains limited by lack of donors and recipient suitability. There remains, therefore, a need for therapies which alleviate the suffering associated with CHF, as well as reducing mortality. Potential strategies under evaluation include anti‐cytokine therapy and inhibitors of neutral endopeptidases, which prevent breakdown of natriuretic peptides. Testosterone therapy has also been proposed as a useful add‐on treatment for men with CHF, although there are currently no clinical data to support this.6 In this article, we review the cardiovascular and neuro‐hormonal actions of testosterone, and discuss how androgen therapy may be of benefit to men with chronic heart failure. No studies have sought specifically to determine gonadal function in men with heart failure. However, several small studies suggest that these patients may have relatively low …

This study was conducted to assess the impact of left ventricular (LV) lead position on longer-term survival after cardiac resynchronization therapy (CRT).An 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.Data 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.An 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% [p0.001]; 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).An 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.

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.

Figure 1. Normal sized ventricle in diastole. In October 2010, a 64 year-old lady with history of well controlled hypertension, previous stroke with no residual weakness and psoriasis attended for a routine tooth extraction. This proved to be a complicated procedure, lasting over an hour, requiring repeated injections of prilocaine and felypressin and resulting in considerable distress to the patient. Fifteen minutes after the procedure finished, the patient experienced central crushing chest pain with radiation to the left arm and her back. She was breathless and sweaty. She attended the emergency department at our institution where examination, initial ECG and chest radiograph were unremarkable. However, her initial troponin level was elevated at 0.54 μg/L (normal < 0.1 μg/L) and measured 1.4 μg/L at 12 hours. Within 24 hours her ECG evolved demonstrating prolongation of the QT interval and lateral T wave inversion. She subsequently underwent coronary angiography, which found smooth normal coronary arteries; left ventriculography demonstrated apical akinesia with basal hyperkinesis (Figs. 1, 2), consistent with tako-tsubo phenomenon. She was treated with aspirin, clopidogrel, bisoprolol, ramipril and atorvastatin and she made a good recovery. Two months later, transthoracic echocardiography showed normal left ventricular size and function. Tako-tsubo was first described in 1991 in patients presenting with cardiac pain, ECG changes consistent with ischemia/infarction, normal coronary angiogram but transient apical akinesis/hypokinesis on left ventriculography [1]. This is thought to arise from catecholamine-mediated epicardial coronary vasoconstriction leading to myocardial stunning, although other theories have been proposed [2, 3]. It is estimated that 1–2% of patients presenting with the clinical picture of an acute myocardial infarction actually suffer from tako-tsubo cardiomyopathy [4]. Typically, tako-tsubo affects post-menopausal females following a significantly stressful event and has been described following bereavement, accidents, physical stress and acute medical illnesses. To our knowledge, this is the first report of tako-tsubo cardiomyopathy occurring apparently as a result of a tooth extraction. Both the significant

Untreated heart failure is a terminal illness with a poor prognosis. β-blockers are an established therapy used to reduce morbidity and mortality. Hypotension and bradycardia often hinder optimal β-blocker administration in patients with chronic heart failure. The efficacy of cardiac resynchronization therapy (CRT) in affecting favorable cardiac remodeling and reducing mortality in heart failure patients with electrical dyssynchrony has been demonstrated in landmark trials only in patients receiving optimal medical therapy. This paper demonstrates the favorable effects of CRT on cardiac hemodynamics facilitating uptitration of β-blocker therapy. It highlights the synergistic relationship of the two therapies and emphasizes the importance of optimizing medical therapy before and after CRT implantation.