Early detection of cancer therapy cardiotoxicity by radionuclide angiography: An update.

Cancer therapy-induced cardiotoxicity is an emerging clinical and healthcare issue. Myocardial dysfunction and heart failure are mostly responsible for increased cardiovascular mortality in cancer disease survivors. Several imaging surveillance techniques have been proposed for early diagnosis of cancer therapy-induced cardiac dysfunction. Our aim was to provide an update of radionuclide angiography applications in this field. Radionuclide angiography is widely used to assess left ventricular ejection fraction (LVEF) throughout cancer treatment, especially in patients with limited acoustic window. Additional prognostic data may be provided by phase analysis and diastolic function evaluation. Low LVEF and high approximate entropy at baseline seem to be predictors for cancer therapy-induced cardiac dysfunction. A decrease in peak filling rate and/or an increase in time to peak filling rate may be observed in patients undergoing anthracycline and/or trastuzumab administration. Diastolic function impairment may precede or not LVEF decrease. In conclusion, recent studies have provided novel insights into the possible role of radionuclide angiography in the early detection of cancer therapy cardiotoxicity. While interpreting the results of a radionuclide angiography examination, an integrated approach combining the evaluation of LVEF, LV diastolic function, and phase analysis may be useful to improve risk stratification of cancer patients treated with cardiotoxic agents.

Pocket histology at cardiac implantable electronic device replacement: What's new?

BACKGROUND: Repeated procedures involving the cardiac implantable electronic device (CIED) pocket increase the infection risk, and the extent of pocket adhesions may prolong the procedure time. Few data on pocket histology at the time of CIED replacement are available. OBJECTIVE: The purpose of this study was to describe CIED pocket histology in a cohort of patients undergoing CIED replacement or upgrade. METHODS: All consecutive patients undergoing CIED replacement or upgrade at our center between November 2019 and May 2020 were enrolled. Subclinical pocket infection was ruled out by physical inspection and laboratory parameters before the procedure. Pocket tissue specimens from the anterior and posterior pockets were obtained intraoperatively. A systematic histological analysis of capsular thickness, fibrous connective tissue, neovascularization, inflammation, and calcifications was performed. RESULTS: Thirty patients (6 women, 20%) were enrolled. The mean capsular thickness was 0.8 ± 0.3 mm in the anterior wall and 1.1 ± 0.4 mm in the posterior wall. Subcapsular fibrosis was mild and multifocal in the anterior wall and moderate and focal in the posterior wall. Neovascularization was focal in most cases, and vessel remodeling mainly involved the tunica media. Chronic inflammation was usually mild and nongranulomatous, and in a quarter of cases, subacute exudative fibrous inflammation was detected in the posterior pocket wall. CONCLUSION: The CIED pocket is a histopathologically dynamic environment, given the coexistence of both a subacute foreign body response and fibrous tissue growth, implying continuous remodeling due to an injury-repair mechanism. Strategies to interact with foreign body response might minimize inflammatory pocket activity, especially device encapsulation by tight fibrous tissue, and possibly complications related to repeated CIED procedures.

Ten-year follow-up of cardiac resynchronization therapy patients with non-ischemic dilated cardiomyopathy assessed by radionuclide angiography: a single-center cohort study.

PURPOSE: Relatively few data are available on long-term survival and incidence of ventricular arrhythmias in cardiac resynchronization therapy (CRT) patients. We investigated long-term outcomes of CRT patients with non-ischemic dilated cardiomyopathy stratified as responders or non-responders according to radionuclide angiography. METHODS: Fifty patients with non-ischemic dilated cardiomyopathy undergoing CRT were assessed by equilibrium Tc99 radionuclide angiography with bicycle exercise at baseline and after 3 months. Intra- and interventricular dyssynchrony were derived by Fourier phase analysis. Patient clinical outcome was assessed after 10 years. RESULTS: At 3 months, 50% of patients were identified as CRT responders according to an increase in LV ejection fraction ≥ 5%. During a follow-up of 109 ± 48 months, 30% of patients died and 6% underwent heart transplantation. Age and history of paroxysmal atrial fibrillation were found to be predictors of all-cause mortality. CRT responders showed lower risk of death from cardiac causes than non-responders. At follow-up, 38% of patients presented at least one episode of sustained ventricular tachycardia, with a similar percentage between responders and non-responders. CONCLUSION: At long-term follow-up, non-ischemic CRT recipients identified as responders by radionuclide angiography were found to be at lower risk of worsening heart failure death than non-responders. Long-term risk for sustained ventricular arrhythmia was similar between CRT responders and non-responders.

Single-photon cardiac imaging in patients with cardiac implantable electrical devices.

Nuclear imaging techniques like single-photon emission computed tomography (SPECT) and radionuclide angiography have wide applications in patients receiving a cardiac implantable electrical device (CIED), who cannot usually undergo cardiac magnetic resonance. Our aim was to provide an update of single-photon imaging clinical applications, with a specific focus on CIED recipients. SPECT imaging is commonly used in CIED patients to assess myocardial perfusion, but it can also be used to evaluate myocardial viability, which is an important predictor of LV function improvement by cardiac resynchronization therapy (CRT). Radionuclide angiography has shown higher temporal resolution and reproducibility than SPECT in the evaluation of cardiac function and dyssynchrony. Left ventricular dyssynchrony as assessed by radionuclide angiography with phase analysis may be reliably used for CRT patient selection and evaluation of CRT response. SPECT imaging with meta-iodo-benzyl-guanidine allows for cardiac sympathetic innervation examination, which may be used for prognostic stratification of heart failure patients and prediction of ventricular tachyarrhythmias. Finally, promising results in CIED infection diagnosis have been shown by SPECT with radiolabeled autologous white blood cells.

Axillary vein access for antiarrhythmic cardiac device implantation: a literature review.

The current narrative review provides an update of available knowledge on venous access techniques for cardiac implantable electronic device implantation, with a focus on axillary vein puncture. Lower procedure-related and lead-related complications have been reported with extrathoracic vein puncture techniques compared with intrathoracic accesses. In particular, extrathoracic lead access through the axillary vein seems to be associated with lower complication incidence than subclavian vein puncture and higher success rate than cephalic vein cutdown. In literature, many techniques have been described for axillary vein access. The use of contrast venography-guided puncture has facilitated the diffusion of the axillary vein approach for device implantation. Venography may be particularly useful in specific demographic and clinical device implantation contexts. Ultrasound-guided or microwire-guided vascular access for lead positioning can be considered a valid alternative to venography, although current applications for axillary vein puncture need further evaluations.

Cardiac implantable electrical devices in patients with hypertrophic cardiomyopathy: single center implant data extracted from the Swedish pacemaker and ICD registry.

Objectives: To investigate cardiac implantable electrical device (CIED) first implants in patients with hypertrophic cardiomyopathy (HCM) in a Swedish tertiary university hospital. Design: Clinical and technical data on pacemaker, implantable cardioverter defibrillator (ICD), and cardiac resynchronization therapy (CRT) first implants performed in HCM patients at the Karolinska University Hospital from 2005 to 2016 were extracted from the Swedish Pacemaker and ICD Registry. Echocardiographic data were obtained by review of hospital recordings. Results: The number of first pacemaker implants in HCM patients was 70 (1.5% of total pacemaker implants). The mean age of HCM pacemaker patients was 71 ± 10 years. Pacemaker implants were almost uniformly distributed between genders. Dual-chamber pacemakers with or without CRT properties were prevalent (6 and 93%, respectively). The number of first ICD implants in HCM patients was 99 (5.1% of total ICD implants). HCM patients receiving an ICD were 53 ± 15 years and prevalently men (70%). Sixty-five (66%) patients were implanted for primary prevention. Dual-chamber ICDs with or without CRT were 21 and 65%, respectively. Obstructive HCM was present in 47% pacemaker patients and 25% ICD patients with available pre-implant echo. Conclusions: This retrospective registry-based study provides a picture of CIED first implants in HCM patients in a Swedish tertiary university hospital. ICDs were the most commonly implanted devices, covering 59% of CIED implants. HCM patients receiving a pacemaker or an ICD had different epidemiological and clinical profiles.

Effects of cardiac resynchronization therapy on right ventricular function during rest and exercise, as assessed by radionuclide angiography, and on NT-proBNP levels.

AIM: We carried out this study to investigate mid-term effects of cardiac resynchronization therapy (CRT) on right ventricular (RV) function and neurohormonal response, expressed by N-terminal pro-brain natriuretic peptide (NT-proBNP), in heart failure patients stratified by baseline RV ejection fraction (RVEF). METHODS AND RESULTS: Thirty-six patients with nonischemic dilated cardiomyopathy underwent technetium-99m radionuclide angiography with bicycle exercise immediately after CRT implantation (during spontaneous rhythm and after CRT activation) and 3 months later. Plasma NT proBNP was assessed before implantation and after 3 months. At baseline, RVEF was impaired (≤35%) in 14 patients, preserved (>35%) in 22. At 3 months, RVEF improved during rest and exercise (P = .02) in patients with impaired RV function, while remaining unchanged in patients with preserved RV function. Rest and exercise RV dyssynchrony decreased in both groups at follow-up (P < .05). A similar mid-term improvement in left ventricular (LV) function and NT-proBNP was observed in patients with impaired and preserved RVEF. In the former, the decrease in NT-proBNP correlated with the improvements both in LV and RV dyssynchrony and functions. CONCLUSION: CRT may improve RV performance, during rest and exercise, and neurohormonal response in heart failure patients with nonischemic dilated cardiomyopathy and baseline RV dysfunction. RV dysfunction should not be considered per se a primary criterion for excluding candidacy to CRT.

Role of cardiovascular imaging in cardiac resynchronization therapy: a literature review.

: Cardiac resynchronization therapy (CRT) is an established treatment in patients with symptomatic drug-refractory heart failure and broad QRS complex on the surface ECG. Despite the presence of either mechanical dyssynchrony or viable myocardium at the site where delivering left ventricular pacing being necessary conditions for a successful CRT, their direct assessment by techniques of cardiovascular imaging, though feasible, is not recommended in clinical practice by the current guidelines. Indeed, even though there is growing body of data providing evidence of the additional value of an image-based approach as compared with routine approach in improving response to CRT, these results should be confirmed in prospective and large multicentre trials before their impact on CRT guidelines is considered.

Five year trends (2008-2012) in cardiac implantable electrical device utilization in five European nations: a case study in cross-country comparisons using administrative databases.

Aims: Common methodologies for analysis of analogous data sets are needed for international comparisons of treatment and outcomes. This study tests using administrative hospital discharge (HD) databases in five European countries to investigate variation/trends in pacemaker (PM) and implantable cardioverter defibrillator (ICD) implant rates in terms of patient characteristics/management, device subtype, and initial implantation vs. replacement, and compares findings with existing literature and European Heart Rhythm Association (EHRA) reports. Methods and results: HD databases from 2008 to 2012 in Austria, England, Germany, Italy and Slovenia were interrogated to extract admissions (without patient identification) associated with PM and ICD implants and replacements, using direct cross-referencing of procedure codes and common methodology to compare aggregate data. 1 338 199 records revealed 212 952 PM and 62 567 ICD procedures/year on average for a 204.4 million combined population, a crude implant rate of about 104/100 000 inhabitants for PMs and 30.6 for ICDs. The first implant/replacement rate ratios were 81/24 (PMs) and 25/7 (ICDs). Rates have increased, with cardiac resynchronization therapy (CRT) subtypes for both devices rising dramatically. Significant between- and within-country variation persists in lengths of stay and rates (Germany highest, Slovenia lowest). Adjusting for age lessened differences for PM rates, scarcely affected ICDs. Male/female ratios remained stable at 56/44% (PMs) and 79/21% (ICDs). About 90% of patients were discharged to home; 85-100% were inpatient admissions. Conclusion: To aid in policymaking and track outcomes, HD administrative data provides a reliable, relatively cheap, methodology for tracking implant rates for PMs and ICDs across countries, as comparisons to EHRA data and the literature indicated.

Less is more: Can we achieve cardiac resynchronization with 2 leads only?

BACKGROUND: We compared clinical and technical outcome of CRT recipients treated either with a conventional 3­leads (3L) CRTD or with the new 2­leads (DX) CRTD that enables atrial signal detection by a floating dipole built on a pentafilar RV lead. METHODS: Echocardiography and cardiopulmonary exercise tests were repeated either before CRTD implantation and between 6 and 12 months follow up in consecutively implanted patients who had a resting heart rate>40bpm at maximum tolerated beta-blocker dosage. HF status, reverse LV remodeling, exercise tolerance and chronotropic incompetence were assessed at 12 months FU. Device diagnostics were obtained twice yearly until December 2016. RESULTS: 37 patients aged 66 (58-73) years were consecutively implanted in 2013-2014 according to current guidelines, 25 with a 3L CRTD and 12 with a DX CRTD. Beta-blocker dosage was similar, and no difference between the 2 groups was observed in terms of NYHA class improvement, LV reverse remodeling, peak cardiopulmonary performance and presence of chronotropic incompetence at 12 months follow up. There was no difference in: amount delivered CRT; occurrence of VT/VF; occurrence of AT/AF. No patients developed need of atrial stimulation at 3-years FU. Atrial undersensing never occurred in any patient, whereas Far-field R-wave oversensing was more common in 3L patient than in DX patients (8/25 vs none, P<0.05). P wave amplitude was greater in DX vs 3L patients [5.1(3.7-9.2) vs 2.9(2-3.9) mV, P<0.01]. CONCLUSION: CRT can be achieved with two­leads-only in the majority of patients, provided that indication to atrial stimulation is ruled out.

Investigating Regional Variation of Cardiac Implantable Electrical Device Implant Rates in European Healthcare Systems: What Drives Differences?

Despite established efficacy for cardiac implantable electrical devices (CIEDs), large differences in CIED implant rates have been documented across and within countries. The aim of this paper is to investigate the influence of socio-economic, epidemiological and supply side factors on CIED implant rates across 57 Regions in 5 EU countries and to assess the feasibility of using administrative data for this purpose. A total of 1 330 098 hospitalizations for CIED procedures extracted from hospital discharge databases in Austria, England, Germany, Italy and Slovenia from 2008 to 2012 was used in the analysis. Higher levels of tertiary education among the labour force and percent of aged population are positively associated with implant rates of CIED. Regional per capita GDP and number of implanting centres appear to have no significant effect. Institutional factors are shown to be important for the diffusion of CIED. Wide variation in CIED implant rates across and within five EU countries is undeniable. However, regional factors play a limited part in explaining these differences with few exceptions. Administrative databases are a valuable source of data for investigating the diffusion of medical technologies, while the choice of appropriate modelling strategy is crucial in identifying the drivers for variation across countries. © 2017 The Authors. Health Economics published by John Wiley & Sons, Ltd.

Effect of Cardiac Resynchronization Therapy on Left Atrial Size and Function as Expressed by Speckle Tracking 2-Dimensional Strain.

Changes in left atrial (LA) strain in patients treated with cardiac resynchronization therapy (CRT) remain not entirely explored. We prospectively evaluated long-term changes in LA size and function and their relation with left ventricular (LV) reverse remodeling and noninvasive hemodynamic variables in patients treated with CRT by 2-dimensional speckle tracking echocardiography. Thirty patients (62 ± 11 years, 63% men) underwent 2-dimensional speckle tracking echocardiography before implant and after 12 months. LA area, global and regional LA strains, LV ejection fraction (LVEF) and longitudinal strain, mitral regurgitation (MR), and diastolic variables were evaluated. At 12 months, CRT responders (60%) exhibited an increase in LA strain (11.4 ± 6.5% vs 16.5 ± 7.9%, p <0.001) and a reduction in LA area (p = 0.002), which were associated with an improvement in MR, E/E' ratio, LVEF, and LV longitudinal strain. In nonresponders, a worsening in LA strain (11.4 ± 6.8% vs 8.7 ± 4.6%, p = 0.017) and LA area (p = 0.002) occurred in parallel with an increase in E/E', whereas LVEF and LV longitudinal strain were unchanged. In conclusion, over long-term follow-up, LA size and strain improved in CRT responders, while worsening in nonresponders. Changes in LV function, filling pressures, and MR seem to be related to LA reverse remodeling, giving a feedback loop.

Battery drain in daily practice and medium-term projections on longevity of cardioverter-defibrillators: an analysis from a remote monitoring database.

AIMS: The longevity of generators is a crucial determinant of the cost-effectiveness of therapy with implantable cardioverter-defibrillators (ICDs) and cardiac resynchronization therapy defibrillators (CRT-D). We evaluated the trend of device-measured residual battery capacity and longevity projections over 5-year follow-up. We also investigated possible factors associated with battery drain. METHODS AND RESULTS: Data from 4851 patients in the European LATITUDE(®) database who were followed up for a minimum of 3 years were analysed. The factors associated with battery drain (i.e. year-to-year decrease in residual battery capacity), and thus potentially impacting on device longevity, were mainly the pacing parameters in CRT-D devices and the number of shocks delivered and diverted in both ICD and CRT-D (all P < 0.01 on linear regression analysis). Over the first 5 years, the longevity estimates provided by devices showed low intra-patient variability and increased with time. The estimates exceeded 10 years for CRT-D and 13 and 12 years for single- and dual-chamber ICDs, respectively. In CRT-D patients, the expected patient age on replacement was 80 ± 12 years, and the expected probability of undergoing device replacement was 63 ± 13% for New York Heart Association (NYHA) II patients and 37 ± 16% for NYHA III patients. For comparison, the probabilities of replacing a CRT-D lasting 5 years were 78 ± 8 and 59 ± 13%, respectively (both P < 0.001). CONCLUSION: Battery drain was mainly associated with pacing output in CRT-D devices and with the number of capacitor charges in both ICD and CRT-D devices. The longevity estimates provided by the devices were consistent and conservative. According to these estimates, among CRT-D recipients a low proportion of patients should require device replacement.

Implant rates of cardiac implantable electrical devices in Europe: A systematic literature review.

BACKGROUND: In recent years, indications for cardiac implantable electrical devices (CIEDs) have broadened; however, budget constraints can significantly impact patient access to these life-saving health technologies. OBJECTIVE: To perform a systematic literature review on the implant rates of pacemakers, cardioverter-defibrillators, and cardiac resynchronization therapy devices in Europe over the last decade to provide insight into the possible reasons for differences across regions or countries. METHODS: Four electronic databases were searched to find studies describing CIED implant rates in Europe. Fifty-eight studies were included. RESULTS: An overview showed a recent rise in CIED implants, with large geographic differences. The ratio between the regions with the highest and lowest implant rates within the same country ranged between 1.3 and 3.4 for pacemakers and between 1.7 and 44.0 for defibrillators. The ratio between the countries with the highest and lowest implant rates ranged between 2.3 and 87.5 for pacemakers, between 3.1 and 1548.0 for defibrillators, and between 4.1 and 221.0 for resynchronization therapy devices. Implant rate variability appears to be influenced by health care, economic, demographic, and cultural factors. CONCLUSION: Publications on CIED implant rates in Europe show a wide variability within and across countries, the determinants of which are only partially investigated. Policy making should improve regarding equity of access to better care.

Non-valvular atrial fibrillation: potential clinical implications of the heterogeneous definitions used in trials on new oral anticoagulants.

AIMS: To evaluate the potential impact of the different definitions of non-valvular atrial fibrillation reported in the literature and to analyse the possible implications for eligibility for novel oral anticoagulants (NOACs) in clinical practice. METHODS: We derived the definitions of 'non-valvular atrial fibrillation' from the exclusion criteria of the trials on NOACs, and then assessed the number and percentage of patients fulfilling the various definitions in a cohort of 500 consecutive atrial fibrillation patients, undergoing clinical and echocardiographic evaluation in our cardiology department, as either in-patients or out-patients. RESULTS: Among the 500 atrial fibrillation patients (mean age 71.2 ±â€Š12.6 years), with permanent atrial fibrillation in 45.2% of the cases, hypertension was very common, either as the main diagnosis or as an associated disease. Valvular heart disease as the main diagnosis (including valvular prosthesis) accounted for 22.8% of the cases. At the echocardiographic evaluation, valvular alterations were very common, especially mitral regurgitation (present, with a variable degree of severity in 63.6% of the cases). Application of the RE-LY exclusion criteria with regard to valvular disease resulted in 116 (23.2%) patients of our cohort classified as valvular atrial fibrillation. This percentage was reduced to 12.2 and 8.8% if ROCKET-AF and ARISTOTLE/ENGAGE-AF criteria, respectively, were applied. CONCLUSIONS: Non-valvular atrial fibrillation is a common clinical entity, but without a unified definition in the literature. The impact in daily practice of the different definitions adopted in trials is noteworthy, since in one patient out of seven, the eligibility for NOACs can be questioned, simply as a consequence of adopting a more or less restrictive definition.

Asymptomatic lone atrial fibrillation - how can we detect the arrhythmia?

Atrial fibrillation (AF) may occur in the absence of identifiable causes, co-morbidities or structural cardiac disease (lone AF). Silent AF is common and patients may have a completely asymptomatic arrhythmia or may experience both symptomatic and asymptomatic AF episodes. It has been estimated that among patients with recognized AF, one third has no appreciable symptoms. In contemporary clinical practice, AF remains largely underdiagnosed and 25% of patients with AF-associated cardioembolic stroke have not been previously diagnosed with AF. The strategies for AF screening include opportunistic and systematic screening. Several methods for AF detection are nowadays available: from very simple (pulse palpation) to more advanced technologies proposed for ambulatory external monitoring of variable time duration. In patients previously implanted with cardiac electrical devices with an atrial lead, according to current clinical indications, the ability to continuously detect AF and to monitor its evolution is magnified, and AF burden can be precisely measured and monitored along with time. Similar information on AF burden can be also obtained by implantation of subcutaneous cardiac monitors that rely on the analysis of consecutive RR intervals for the diagnosis of AF. The prognosis is generally favorable for patients presenting with lone AF, but adverse outcomes, including stroke and thromboembolic events may occur at long term, in association with aging, or the development of underlying heart disease, or progression from paroxysmal to permanent AF. In this respect, the role of new technologies and diagnostic tools for AF detection and monitoring should be fully defined.

Current use of implantable electrical devices in Sweden: data from the Swedish pacemaker and implantable cardioverter-defibrillator registry.

AIMS: The National Swedish Pacemaker and Implantable Cardioverter-Defibrillator (ICD) Registry collects prospective data on all pacemaker and ICD implants in Sweden. We aimed to report the 2012 findings of the Registry concerning electrical devices implantation rates and changes over time, 1 year complications, long-term device longevity and patient survival. METHODS AND RESULTS: Forty-four Swedish implanting centres continuously contribute implantation of pacemakers and ICDs to the Registry by direct data entry on a specific website. Clinical and technical information on 2012 first implants and postoperative complications were analysed and compared with previous years. Patient survival data were obtained from the Swedish population register database. In 2012, the mean pacemaker and ICD first implantation rates were 697 and 136 per million inhabitants, respectively. The number of cardiac resynchronization therapy (CRT) first implantations/million capita was 41 (CRT pacemakers) and 55 (CRT defibrillators), with only a slight increase in CRT-ICD rate compared with 2011. Most device implantations were performed in men. Complication rates for pacemaker and ICD procedures were 5.3 and 10.1% at 1 year, respectively. Device and lead longevity differed among manufacturers. Pacemaker patients were older at the time of first implant and had generally worse survival rate than ICD patients (63 vs. 82% after 5 years). CONCLUSION: Pacemaker and ICD implantation rates seem to have reached a level phase in Sweden. Implantable cardioverter-defibrillator and CRT implantation rates are very low and do not reflect guideline indications. Gender differences in CRT and ICD implantations are pronounced. Device and patient survival rates are variable, and should be considered when deciding device type.