Miniaturized implantable cardiac monitor with a long sensing vector (BIOMONITOR III): Insertion procedure assessment, sensing performance, and home monitoring transmission success.

BACKGROUND: Implantable Cardiac Monitors (ICMs) are used for long-term monitoring of arrhythmias. BIOMONITOR III is a novel ICM with a miniaturized profile, long sensing vector due to a flexible antenna, simplified implantation with a dedicated insertion tool for pocket formation and ICM placement in a single step, and daily automatic Home Monitoring (HM) function. METHODS: In 47 patients undergoing BIOMONITOR III insertion for any ICM indication, 16 investigators at 10 Australian sites assessed handling characteristics of the insertion tool, R-wave amplitudes, noise burden, P-wave visibility, and HM transmission success. Patients were followed for 1 month. RESULTS: All 47 attempted insertions were successful. Median time from skin incision to removal of the insertion tool after ICM insertion was 39 s (IQR 19-65) and to wound closure and cleaning was 4.7 min (IQR 3.5-7.8). All aspects of the insertion tool were rated as "good" or "excellent" in ≥97.9% and "fair" in ≤2.1% of patients, except for "force needed for tunnelling" (91.5% good/excellent, 8.5% fair). Based on HM data, R-waves in the first month were stable at 0.70 ± 0.37 mV. Median noise burden (disabling automatic rhythm evaluation) was 0.19% (IQR 0.00-0.93), equivalent to 2.7 min (IQR 0.0-13.4) per day. In HM-transmitted ECG strips with regular sinus rhythm, P-waves were visible in 89 ± 24% of heart cycles. Patient-individual automatic Home Monitoring transmission success was 98.0% ± 5.5%. CONCLUSIONS: The novel ICM performed well in all aspects studied, including fast insertion, reliable R-wave sensing, good P-wave visibility, and highly successful HM transmissions.

QRS Fragmentation and QTc Duration Relate to Malignant Ventricular Tachyarrhythmias and Sudden Cardiac Death in Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: QRS fragmentation (fQRS) and prolonged QTc interval on surface ECG are prognostic in various cardiomyopathies other than hypertrophic cardiomyopathy (HCM). The association between fQRS and prolonged QTc duration with occurrence of ventricular tachyarrhythmias or sudden cardiac death (VTA/SCD) in patients with HCM was explored. METHODS AND RESULTS: One hundred and ninety-five clinical HCM patients were studied. QTc duration was derived applying Bazett's formula; fQRS was defined as presence of various RSR' patterns, R or S notching and/or >1 additional R wave in any non-aVR lead in patients without pacing or (in)complete bundle branch block. The endpoints comprised SCD, ECG documented sustained VTA (tachycardia or fibrillation) or appropriate implantable cardioverter defibrillator (ICD) therapies (antitachycardia pacing [ATP] or shock) for VTA in ICD recipients (n = 58 [30%]). QT prolonging drugs recipients were excluded. After a median follow-up of 5.7 years (IQR 2.7-9.1), 26 (13%) patients experienced VTA or SCD. Patients with fQRS in ≥3 territories (inferior, lateral, septal, and/or anterior) (p = 0.004) or QTc ≥460 ms (p = 0.009) had worse cumulative survival free of VTA/SCD than patients with fQRS in <3 territories or QTc <460 ms. fQRS in ≥3 territories (ß 4.5, p = 0.020, 95%CI 1.41-14.1) and QTc ≥460 ms (ß 2.7, p = 0.037, 95%CI 1.12-6.33) were independently associated with VTA/SCD. Likelihood ratio test indicated assessment of fQRS and QTc on top of conventional SCD risk factors provides incremental predictive value for VTA/SCD (p = 0.035). CONCLUSIONS: Both fQRS in ≥3 territories and QTc duration are associated with VTA/SCD in HCM patients, independently of and incremental to conventional SCD risk factors.

Geometry of left atrial appendage assessed with multidetector-row computed tomography: implications for transcatheter closure devices.

AIMS: To assess the left atrial appendage (LAA) geometry with multidetector-row computed tomography (MDCT) and its implications for selection of closure devices. METHODS AND RESULTS: One hundred and ninety-seven patients who underwent MDCT prior to catheter ablation for atrial fibrillation were evaluated. Feasibility for Watchman and Amplatzer Cardiac Plug (ACP) devices was assessed based on the maximal cross-sectional diameter and perimeter of the ostium and at 10 mm depth and on the LAA diameter on the MDCT plane resembling the transoesophageal echocardiography (TEE) view. Mean maximal diameters of the ostium and at 10 mm depth were 28.7±4.4 mm and 24.6±4.5 mm, respectively, resulting in feasibilities of 80.7%, 84.8% and 91.4% for the Watchman, the ACP and for either one of the two devices, respectively. Mean perimeters of the ostium and at 10 mm depth were 79.1±12.2 mm and 69.8±11.6 mm, resulting in feasibilities of 87.8%, 92.9% and 96.4% for the Watchman, the ACP and for either one of the two devices, respectively. Mean TEE-like MDCT LAA diameter was 22.0±3.3 mm, resulting in feasibilities of 93.9%, 97% and 99.0% for the Watchman, the ACP and for either one of the two devices, respectively. CONCLUSIONS: The feasibility of current devices is high, based on MDCT measurements of the LAA, with no difference for either one of the devices.

Increased myocardial methionine-enkephalin with reduced arterial oxygenation in congenital heart disease.

BACKGROUND: Cardiac opioid peptides have been identified to exert important adaptive metabolic signalling for cardioprotection against ischaemia or hypoxia-related injury. AIMS: To determine myocardial methionine-enkephalin content in children with hypoxemic congenital heart defects and to correlate myocardial content of methionine-enkephalin with the extent of arterial oxygen desaturation. METHODS: Children (n= 20, median age of 16 months), undergoing cardiac surgical repair (tetralogy of Fallot, 17/20), were included in this study. Arterial oxygen saturation was measured on admission. Myocardial samples obtained during surgery were assayed via radioimmunochemistry for methionine-enkephalin content. RESULTS: Greater methionine-enkephalin content was measured in the right ventricles of the patients suffering from recent cyanotic spells compared with those with no recent spells (cyanotic spells: 2418 ± 844 pg/g wet weight tissue, n= 6; no spells: 1175 ± 189 pg/g wet weight tissue, n= 14, P= 0.04). An inverse correlation was evident between the arterial oxygen saturation and myocardial methionine-enkephalin content. CONCLUSION: Myocardial methionine-enkephalin levels increase with the severity of hypoxic stress in congenital cardiac disease and may play an important adaptive role in countering adrenergic over-activity and related excess demand on myocardial metabolic capacity.

Augmented myocardial methionine-enkephalin in a murine model of cardiac angiotensin II-overexpression.

INTRODUCTION: The endogenous opioid system has been reported to interact with both the cardiac sympathetic and renin-angiotensin systems in exerting a local regulatory action on the heart. The goal of this investigation was to examine how cardiac levels of enkephalin production are altered in the development of normotensive primary hypertrophy due to elevated intra-cardiac angiotensin II (Ang II) production. METHODS: Atrial and ventricular methionine-enkephalin (ME) levels were measured by quantitative radioimmunoassay in 14 and 28-week-old male transgenic mice (TG1306/1R) and control mice. The TG1306/1R exhibit cardiac specific Ang II overexpression and cardiac hypertrophy, but not hypertension. RESULTS: TG1306/1R mice had significantly higher heart/body weight ratios (15-20%) than control littermates at both 14 (p=0.02) and 28 weeks (p=0.04). Relative to controls, ME content was significantly elevated (approximately two-fold) in atria and ventricles in the older 28-week TG1306/1R mice only. A significant inverse correlation between heart size and ME level was observed for 28-week TG1306/1R only. CONCLUSIONS: We have provided evidence that a marked elevation of myocardial enkephalin level is observed in the established (but not early) phase of cardiac hypertrophy associated with cardiac-specific Ang II-overexpression. This study identifies a potentially important relationship between two endogenous peptidergic signalling systems involved in the regulation of growth and function of the hypertrophic heart.

Cross-talk of opioid peptide receptor and beta-adrenergic receptor signalling in the heart.

Opioid peptide receptor (OPR) and beta-adrenergic receptor (beta-AR) are well-established members of G-protein-coupled receptor (GPCR) superfamily and are involved in regulating cardiac contractility, energy metabolism, myocyte survival or death. OPRs are typical Gi/Go-coupled receptors and activated by opioid peptides derived from the endorphin, dynorphin and enkephalin families, whereas beta-AR stimulated by catecholamines is the model system for Gs-coupled receptors. While it is widely accepted that beta-AR stimulation serves as the most powerful means to increase cardiac output in response to stress or exercise, we have only begun to appreciate functional roles of OPR stimulation in regulating cardiovascular performance. Cardiovascular regulatory effects of endogenous opioids were initially considered to originate from the central nervous system and involved the pre-synaptic co-release of norepinephrine with enkephalin from sympathetic neuronal terminals in the heart. However, opioid peptides of myocardial origin have been shown to play important roles in local regulation of the heart. Notably, OPR stimulation not only inhibits cardiac excitation-contraction coupling, but also protects the heart against hypoxic and ischemic injury via activation of Gi-mediated signalling pathways. Further, OPRs functionally and physically cross-talk with beta-ARs via multiple hierarchical mechanisms, including heterodimerization of these receptors, counterbalance of functional opposing G protein signalling, and interface at downstream signalling events. As a result, the beta-AR-mediated positive inotropic effect and increase in cAMP are markedly attenuated by OPR activation in isolated cardiomyocytes as well as sympathectomized intact rat hearts. This brief review will focus on the interaction between beta-AR and OPR and its potential physiological and pathophysiological relevance in the heart.

Endogenous cardiac opioids: enkephalins in adaptation and protection of the heart.

Opiates have been used for thousands of years in the form of opium for relief of pain or fever and to induce sleep. However, it was only in the 1970s that the endogenous ligands for the opiate receptors were identified and termed opioid peptides. Opioid peptides activate G protein-coupled receptors in the central and autonomic nervous system, with marked effects on the regulation of pain perception, body temperature, respiration, heart rate and blood pressure. Cardiovascular regulatory effects of endogenous opioids were initially considered to originate from neural centres in the central nervous system, facilitating a regulatory role in neuro-transmission, as demonstrated by the presynaptic co-release from sympathetic neurones of norepinephrine with enkephalin or acetylcholine with enkephalin. However, opioid peptides of myocardial origin have also recently been shown to play a key role in local regulation of the heart. This brief review highlights the key features of the enkephalin opioids in the heart and the current understanding of their role in development, ageing, cardioprotection, hypertension, hypertrophy, and heart failure.