Michela Brambatti

Temporal Relationship Between Subclinical Atrial Fibrillation and Embolic Events

Background— Among patients with implantable pacemakers and defibrillators, subclinical atrial fibrillation (SCAF) is associated with an increased risk of stroke; however, there is limited understanding of their temporal relationship. Methods and Results— The Asymptomatic Atrial Fibrillation and Stroke Evaluation in Pacemaker Patients and the Atrial Fibrillation Reduction Atrial Pacing Trial (ASSERT) enrolled 2580 pacemaker and defibrillator patients aged ≥65 years with a history of hypertension but without a history of atrial fibrillation. Pacemakers and implantable cardioverter-defibrillators precisely logged the time and duration of all episodes of SCAF and recorded electrograms that were adjudicated by experts. We examined the temporal relationship between SCAF >6 minutes in duration and stroke or systemic embolism. Of 51 patients who experienced stroke or systemic embolism during follow-up, 26 (51%) had SCAF. In 18 patients (35%), SCAF was detected before stroke or systemic embolism. However, only 4 patients (8%) had SCAF detected within 30 days before stroke or systemic embolism, and only 1 of these 4 patients was experiencing SCAF at the time of the stroke. In the 14 patients with SCAF detected >30 days before stroke or systemic embolism, the most recent episode occurred at a median interval of 339 days (25th to 75th percentile, 211–619) earlier. Eight patients (16%) had SCAF detected only after their stroke, despite continuous monitoring for a median duration of 228 days (25th to 75th percentile, 202–719) before their event. Conclusions— Although SCAF is associated with an increased risk of stroke and embolism, very few patients had SCAF in the month before their event. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00256152.

Comparison of dabigatran versus warfarin in diabetic patients with atrial fibrillation: Results from the RE-LY trial

OBJECTIVE Diabetes mellitus (DM) is frequent among patients with atrial fibrillation (AF). The RE-LY trial permits evaluation of patient characteristics, outcomes and the effectiveness of dabigatran etexilate among diabetic individuals. METHODS Patient characteristics and outcomes were compared between diabetic and non-diabetic patients and the relative efficacy of each dose of dabigatran (150 mg bid and 110 mg bid) versus warfarin was evaluated. RESULTS Of 18,113 patients in RE-LY, 4221 patients (23.3%) had DM. Patients with DM were younger (70.9 vs. 71.7 years), more likely to have hypertension (86.6% vs. 76.5%), coronary artery disease (37.4% vs. 24.9%) and peripheral vascular disease (5.6% vs. 3.2%); (all p<0.01). Time in therapeutic range for warfarin-treated patients was 65% for diabetic versus 68% for non-diabetic patients (p<0.001). Regardless of assigned treatment, stroke or systemic embolism was more common among patients with DM (1.9% per year vs. 1.3% per year, p<0.001). DM was also associated with an increased risk of death (5.1% per year vs. 3.5% per year, p<0.001) and major bleeding (4.2% per year vs. 3.0% per year, p<0.001). The absolute reduction in stroke or systemic embolism with dabigatran compared to warfarin was greater among patients with DM than those without DM (dabigatran 110 mg: 0.59% per year vs. 0.05% per year; dabigatran 150 mg: 0.89% per year vs. 0.51% per year). CONCLUSIONS Compared to non-DM patients, AF patients with DM derive a greater absolute risk reduction in embolic events when treated with dabigatran. ClinicalTrials.gov Identifier: NCT00262600.

Management of patients with implantable cardioverter-defibrillators and pacemakers who require radiation therapy

BACKGROUND Radiation therapy (RT) may pose acute and long-term risks for patients with cardiac implantable electronic devices (CIEDs), including pacemakers (PMs) and implantable cardioverter-defibrillators (ICDs). However, the frequency of these problems has not been accurately defined. OBJECTIVE The purpose of this study was to determine the prevalence of CIEDs among patients requiring RT and report the common CIED-related problems when patients are managed according to a standard clinical care path. METHODS In a single tertiary-care center, we prospectively screened all patients requiring RT and identified patients with ICDs or PMs. We collected clinical data about their cancer, RT treatment plan, and CIED. Radiation dose to the device was estimated in all patients, and any device malfunction during RT was documented. RESULTS Of the 34,706 consecutive patients receiving RT, 261 patients (0.8%, mean age 77.9 ± 9.4 years) had an implantable cardiac device: 54 (20.7%) ICDs and 207 (79.3%) PMs. The site of RT was head and neck (27.4%), chest (30.0%), and abdomen/pelvis (32.6%). Using our care path, 63.2% of patients required continuous cardiac monitoring, 14.6% required device reprogramming, 18.8% required magnet application during RT, and 3.4% required device repositioning to the contralateral side before RT. Four patients (1.5%) had inappropriate device function during RT: 3 experienced hemodynamically tolerated ventricular pacing at the maximum sensor rate, and 1 experienced a device power-on-reset. No patient died or suffered permanent device failure. CONCLUSION Nearly 1% of patients receiving RT in this series has a PM or ICD. However, with a systematic policy of risk assessment and patient management, significant device-related complications are rare.

Cardiac resynchronization therapy improves ejection fraction and cardiac remodelling regardless of patients' age

AIMS Cardiac resynchronization therapy (CRT) improves symptoms and reduces mortality in heart failure (HF) patients, but little data exist on the efficacy of CRT in the elderly. The aim of our study is to define CRT-related benefits in terms of left ventricular ejection fraction (LVEF) improvement in two subgroups of patients (<75 and ≥75 years old) and test possible differences between these two groups. METHODS AND RESULTS Single-centre prospective observational study including 65 patients with optimally treated, advanced HF and indication to CRT. All patients were investigated with clinical evaluation, Minnesota Living with Heart Failure Questionnaire (MLHFQ), 12-lead electrocardiogram, and full echocardiographical study before CRT implant and 3 and 12 months after. Left ventricular ejection fraction showed a time-related improvement in the whole population (+10.6% over 12 months) as well as in each subgroup. The magnitude of LVEF improvement was similar in elderly and non-elderly patients (+13.6 vs. +7.9%; P = ns). Left ventricular diameters, pulmonary artery systolic pressure, New York Heart Association class, MLHFQ score, and QRS width all showed a time-related improvement in the whole population as well as in each subgroup. End-diastolic left ventricular diameter remodelling and QRS width reduction were significantly more pronounced in the elderly, whereas other clinical and instrumental secondary endpoints showed a similar improvement between ≥75 and <75 years old patients. There was no significant difference regarding mortality between elderly and non-elderly patients. CONCLUSION Cardiac resynchronization therapy is as effective in improving LVEF in elderly as in non-elderly patients. Age alone should not be a determinant to restrict resynchronization therapy in HF patients.

Periprocedural Management of Oral Anticoagulation in Patients With Atrial Fibrillation: Approach in the Era of New Oral Anticoagulants

A growing number of patients with atrial fibrillation are treated with oral anticoagulation (OAC), and a large proportion of them will require surgical or other invasive procedures. These procedures typically involve interruption of OAC with or without the use of heparin bridging; however; there has been a dramatic change in this practice during the past 3 years. The introduction of short-acting, new oral anticoagulants and the growing popularity of some low-risk procedures with continued OAC have transformed our practice. Physicians and surgeons who treat patients with atrial fibrillation must be aware of these changes and understand how to deal with the new challenges they may encounter.

Eosinophilic myocarditis: a paraneoplastic event

2546 www.thelancet.com Vol 385 June 20, 2015 In September, 2014, a 55-year-old woman presented to our emergency department with a 2 month history of worsening dyspnoea. She was a smoker with a 19 packyear history but no other risk factors for pulmonary or cardiovascular disease. On examination her blood pressure was 90/60 mm Hg, heart rate 130 beats per min, and oxygen saturation 92% on room air. She had jugular venous distension and reduced breath sounds bilaterally but no pitting oedema of the legs. Laboratory tests showed an increased leucocyte count (18·9 × 109/L) with neutrophilia (79%) and normal eosinophils, raised C-reactive protein (36 mg/L), and raised troponin T (354 ng/L). Electrocardiogram (ECG) showed sinus tachycardia with low voltage pattern. Chest radiograph showed cardiomegaly and bilateral pleural eff usions. On echocardiography we saw a severe circumferential pericardial eff usion with signs of cardiac tamponade and immediately did evacuative pericardiocentesis, draining 650 mL of serosanguineous pericardial fl uid. Echocardiography after pericardiocentesis showed a left ventricle with normal dimensions but severe systolic dysfunction (left ventricular ejection fraction [LVEF] 25%), and a severely dilated hypokinetic right ventricle with normal pulmonary artery systolic pressure. CT scan confi rmed large bilateral pleural eff usions and showed a 40 mm hypodense lesion surrounding the right main bronchus (fi gure). 24 h after admission the patient developed cardiogenic shock with acute respiratory failure. We did evacuative thoracentesis, draining 1 L of serous pleural fl uid, and coronary angiography, which ruled out artery stenosis. We inserted an intra-aortic balloon pump and started vasopressor inotropes (dopamine and adrenaline), intravenous furosemide, and tracheal mechanical ventilation. Urgent right ventricular endomyocardial biopsy samples showed acute eosinophilic myocarditis (fi gure). We started intravenous methylprednisolone 1 g daily for 3 days followed by oral prednisone 50 mg daily. Cardiogenic shock resolved quickly and after 5 days the intra-aortic balloon pump was removed and she was extubated the next day when LVEF was 45%. 12 days after admission LVEF had further improved to 53%. Analysis of the pericardial fl uid showed adenocarcinoma-like cells although there were no malignant cells in the pleural fl uid. Further investigations confi rmed lung cancer and our patient was fi nally given a diagnosis of stage IV lung adenocarcinoma (wild-type EGFR/ALK) with cerebral metastases. She continued taking oral steroids (dexa methasone 4 mg daily) for the brain metastases and myocarditis and began cisplatin and pemetrexed chemo therapy. In March, 2015, after six cycles of chemotherapy, LVEF was 59% and the pulmonary and brain lesions were reduced in size. At last follow-up in May, 2015, 2 months after the last treatment, the pulmonary lesions had progressed. Eosinophilic myocarditis is a rare form of myocardial infl ammation, a life-threating condition with a variable presentation characterised by eosinophilic infi ltration of the myocardium, associated with systemic disorders such as parasitic infection, hypersensitivity reaction to drugs, eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, and malignancy. Eosinophilic myocarditis as a paraneoplastic occurrence is very rare. The pathogenesis is unclear; one explanation might be bone marrow stimulation via interleukin-5 (IL-5) secreted by the tumour itself, associated with peripheral hypereosinophilia. IL-5 can also be produced by eosinophils in the myocardial tissue, playing a part in both chemoattraction and degranulation, which might explain local injury without peripheral hypereosinophilia. Our patient did not present with typical features of eosinophilic myocarditis. Cardiac symptoms, raised cardiac enzymes, and severe cardiac dysfunction despite normal coronary angiography pointed to the diagnosis, but the enlarged right ventricle and absence of peripheral hypereosinophilia were unusual. We established defi nitive diagnosis on the basis of endomyocardial biopsy and started steroids early, which helped to restore cardiac contractility and enabled her to start chemotherapy.

Feasibility of a cardiologist-only approach to sedation for electrical cardioversion of atrial fibrillation: A randomized, open-blinded, prospective study

BACKGROUND/OBJECTIVES Sedation with propofol should be administered by personnel trained in advanced airway management. To overcome this limitation, the use of short acting benzodiazepines by cardiologists spread widely, causing concerns about the safety of this procedure in the absence of anesthesiology assistance. The aim of the study was to compare feasibility of a cardiologist-only approach with an anesthesiologist-assisted sedation protocol during elective direct-current cardioversion (DCC) of persistent atrial fibrillation (AF). METHODS This prospective, open-blinded, randomized study included 204 patients, which were admitted for scheduled cardioversion of persistent AF, and randomized in a 1:1 fashion to either propofol or midazolam treatment arm. Patients in the propofol group underwent DCC with anesthesiologist assistance, while patients in the midazolam group saw the cardiologist as the only responsible for both sedation and DCC. RESULTS Twenty-three adverse events occurred: 13 in the propofol group and 10 in the midazolam group (p=NS). Most of them were related to bradyarrhythmias and respiratory depressions. There was no need of intubation or other advanced resuscitation techniques in any of these patients. No differences were found regarding procedure tolerability and safety endpoints between the two groups. DCC procedures with anesthesiology support were burdened by higher delay from scheduled time and higher costs. CONCLUSIONS Sedation with midazolam administered by cardiologist-only appears to be as safe as sedation with propofol and anesthesiologist assistance. Adverse events were few in both groups and easily handled by the cardiologist alone. A cardiologist-only approach to sedation provides less procedural delay, thus being easier to schedule and correlated with fewer costs.

Sleep-disordered Breathing and Atrial Fibrillation: Review of the Evidence

Sleep-disordered breathing and atrial fibrillation are two common medical conditions. A strong association between them has been described and has prompted significant research in understanding the mechanism connecting the two conditions while explaining the synergic negative effects in terms of morbidity and mortality in affected patients. This review focuses first on the pathophysiologic mechanisms favoring the development of atrial fibrillation in patients with sleep-disordered breathing, considering specifically and separately obstructive sleep apnea and central sleep apnea. Then, the effects of these two disorders in specific clinical settings are addressed.

Is Defibrillation Testing Necessary for Implantable Transvenous Defibrillators? Defibrillation Testing Should Not Be Routinely Performed at the Time of Implantable Cardioverter Defibrillator Implantation

Because the implantable cardioverter defibrillator (ICD) was introduced into clinical practice, insertion of these devices has typically involved defibrillation testing (DT). However, DT has never been shown to independently improve patient outcomes. The rationale for DT has always been that the induction of ventricular fibrillation (VF) immediately after ICD insertion allows the implanting team to verify that the ICD can appropriately sense VF and deliver a high-energy shock that can effectively terminate this arrhythmia.1 The first ICD systems were complex, using epicardial patches and monophasic shock waveforms, thus accurate sensing and termination of VF were frequently in question. However, the ICD evolved over time, with the introduction of transvenous systems, biphasic waveforms, and active cans, which made failure to sense and treat VF much less common.2,3 Modern ICDs are also capable of delivering energies >40 J, thus many have started to question the rationale for DT in the modern era.4–7 Response by Russo et al on p 351 During the past 10 years, there has been a dramatic shift in practice, such that DT is performed in <50% of ICD implants in some jurisdictions. This change was not driven by the results of randomized trials, but by changing opinions of clinicians,4 based on the following insights from observational studies: (1) intraoperative DT is usually successful and clinicians do not always act on unfavorable results; (2) intraoperative DT is an unproven surrogate for clinical shock efficacy; (3) the likelihood of a failed appropriate clinical shock is low and does not appear lower among patients who have DT; and (4) DT is associated with uncommon, but serious complications and adds cost and complexity to the ICD implant procedure. A large randomized evaluation of DT will soon be completed8; however, the observational data …Because the implantable cardioverter defibrillator (ICD) was introduced into clinical practice, insertion of these devices has typically involved defibrillation testing (DT). However, DT has never been shown to independently improve patient outcomes. The rationale for DT has always been that the induction of ventricular fibrillation (VF) immediately after ICD insertion allows the implanting team to verify that the ICD can appropriately sense VF and deliver a high-energy shock that can effectively terminate this arrhythmia.1 The first ICD systems were complex, using epicardial patches and monophasic shock waveforms, thus accurate sensing and termination of VF were frequently in question. However, the ICD evolved over time, with the introduction of transvenous systems, biphasic waveforms, and active cans, which made failure to sense and treat VF much less common.2,3 Modern ICDs are also capable of delivering energies >40 J, thus many have started to question the rationale for DT in the modern era.4–7 Response by Russo et al on p 351 During the past 10 years, there has been a dramatic shift in practice, such that DT is performed in <50% of ICD implants in some jurisdictions. This change was not driven by the results of randomized trials, but by changing opinions of clinicians,4 based on the following insights from observational studies: (1) intraoperative DT is usually successful and clinicians do not always act on unfavorable results; (2) intraoperative DT is an unproven surrogate for clinical shock efficacy; (3) the likelihood of a failed appropriate clinical shock is low and does not appear lower among patients who have DT; and (4) DT is associated with uncommon, but serious complications and adds cost and complexity to the ICD implant procedure. A large randomized evaluation of DT will soon be completed8; however, the observational data …

Prospective study of tricuspid valve regurgitation associated with permanent leads in patients undergoing cardiac rhythm device implantation: Background, rationale, and design

Given the increasing numbers of cardiac device implantations worldwide, it is important to determine whether permanent endocardial leads across the tricuspid valve can promote tricuspid regurgitation (TR). Virtually all current data is retrospective, and indicates a signal of TR being increased after permanent lead implantation. However, the precise incidence of moderate or greater TR post-procedure, the exact mechanisms (mechanical, traumatic, functional), and the hemodynamic burden and clinical effects of this putative increase in TR, remain uncertain. We have therefore designed a multicenter, international, prospective study of 300 consecutive patients (recruitment completed, baseline data presented) who will undergo echocardiography and clinical assessment prior to, and at 1-year post device insertion. This prospective study will help determine whether cardiac device-associated TR is real, what are its potential mechanisms, and whether it has an important clinical impact on cardiac device patients.