Usefulness of electroanatomical mapping during transseptal endocardial left ventricular lead implantation

AimFailure rate to implant left ventricular (LV) lead transvenously is 4-8% in cardiac resynchronization therapy (CRT) patients. Epicardial lead placement is an alternative method and if not applicable case reports and small series showed the feasibility of endocardial LV lead implantation. Electroanatomical mapping might be a useful tool to guide this procedure.Methods and resultsFour patients had undergone endocardial LV lead implantation after unsuccessful transvenous implantation or epicardial LV lead dysfunction using the transseptal approach. Electroanatomical mapping was used to mark the location of the transseptal puncture. This location point guided the mapping catheter from the subclavian access and facilitated positioning of the LV lead at the adjacent latest activation area of the left ventricle detected by activation mapping. Endocardial active fixation LV leads were successfully implanted in all patients with stable electrical parameters immediately after implantation and over a mean follow-up of 18.3 months (lead impedance 520 +/- 177 vs. 439 +/- 119 Omega and pacing threshold 0.8 +/- 0.2 V, 0.5 ms vs. 0.6 +/- 0.1 V, 0.5 ms, respectively). Patients were maintained on anticoagulation therapy with a target international normalized ratio of 3.5-4.5 and did not show any thromboembolic, haemorrhagic events, or infection. Echocardiography showed significant improvement of LV systolic function with marked improvement of the functional status.ConclusionsElectroanatomical mapping is a useful technical tool to guide endocardial LV lead implantation. It helps to identify the location of the transseptal puncture and the use of activation mapping might facilitate location of the optimal lead positions during CRT

High rate of in-stent restenosis after coronary intervention in carriers of the mutant mannose-binding lectin allele

BACKGROUND: In-stent restenosis occurs in 10-30% of patients following bare metal stent (BMS) implantation and has various risk factors. Mannose-binding lectin (MBL) is known to have effect on the progression of atherosclerosis. Single nucleotide polymorphisms (SNP) of the MBL2 gene intron 1 (codon 52, 54, 57) are known to modulate the bioavailability of the MBL protein. Our aim was to identify the association of these polymorphisms of the MBL gene in the occurrence of in-stent restenosis after coronary artery bare metal stent implantation. METHODS: In a non-randomized prospective study venous blood samples were collected after recoronarography from 225 patients with prior BMS implantation. Patients were assigned to diffuse restenosis group and control group based on the result of the coronarography. MBL genotypes were determined using quantitative real-time PCR. Proportion of different genotypes was compared and adjusted with traditional risk factors using multivariate logistic regression. RESULTS: Average follow-up time was 1.0 (+ - 1.4) year in the diffuse restenosis group (N = 117) and 2.7 (+ - 2.5) years in the control group (N = 108). The age, gender distribution and risk status was not different between study groups. Proportion of the MBL variant genotype was 26.8% (29 vs. 79 normal homozygous) in the control group and 39.3% (46 vs. 71 normal homozygous) in the restenosis group (p = 0.04). In multivariate analysis the mutant allele was an independent risk factor (OR = 1.96, p = 0.03) of in-stent restenosis. CONCLUSIONS: MBL polymorphisms are associated with higher incidence of development of coronary in-stent restenosis. The attenuated protein function in the mutant allelic genotype may represent the underlying mechanism

Management of upper airway edema caused by hereditary angioedema

Hereditary angioedema is a rare disorder with a genetic background involving mutations in the genes encoding C1-INH and of factor XII. Its etiology is unknown in a proportion of cases. Recurrent edema formation may involve the subcutis and the submucosa - the latter can produce obstruction in the upper airways and thereby lead to life-threatening asphyxia. This is the reason for the high, 30-to 50-per-cent mortality of undiagnosed or improperly managed cases. Airway obstruction can be prevented through early diagnosis, meaningful patient information, timely recognition of initial symptoms, state-of-the-art emergency therapy, and close monitoring of the patient. Prophylaxis can substantially mitigate the risk of upper airway edema and also improve the patients' quality of life. Notwithstanding the foregoing, any form of upper airway edema should be regarded as a potentially life-threatening condition. None of the currently available prophylactic modalities is capable of preventing UAE with absolute certainty

Frequency of the virilising effects of attenuated androgens reported by women with hereditary angioedema.

BACKGROUND: Danazol, a drug extensively used in the management of hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE), has various side effects. This study investigated the virilizing actions of this drug in 31 danazol-treated female patients with HAE-C1-INH. We compared our findings with those of healthy controls and with literature data. METHODS: The patients were interviewed individually about the type and severity of the virilizing effects, as well as about their satisfaction with danazol therapy. RESULTS: The average duration of danazol treatment was 10.31 years [2 to 23] and its mean daily dose was 131.7 mg [33 to 200]. The most common adverse effects were hirsutism (n = 14), weight gain (n = 13), and menstrual disturbances (n = 8). The severity of danazol adverse effects did not differ by duration of treatment or by daily drug dose. The mean level of patient satisfaction with the treatment was high. The comparison of age-matched healthy controls and of HAE-C1-INH patients receiving danazol did not demonstrate a statistically higher incidence of any of the monitored symptoms in the danazol group. CONCLUSIONS: Our findings indicate that long-term danazol treatment – using the lowest effective dose – has only a mild virilizing effect

New treatments addressing the pathophysiology of hereditary angioedema

Hereditary angioedema is a serious medical condition caused by a deficiency of C1-inhibitor. The condition is the result of a defect in the gene controlling the synthesis of C1-inhibitor, which regulates the activity of a number of plasma cascade systems. Although the prevalence of hereditary angioedema is low – between 1:10,000 to 1:50,000 – the condition can result in considerable pain, debilitation, reduced quality of life, and even death in those afflicted. Hereditary angioedema presents clinically as cutaneous swelling of the extremities, face, genitals, and trunk, or painful swelling of the gastrointestinal mucosa. Angioedema of the upper airways is extremely serious and has resulted in death by asphyxiation

Safety of pulsed field ablation in more than 17,000 patients with atrial fibrillation in the MANIFEST-17K study

Pulsed field ablation (PFA) is an emerging technology for the treatment of atrial fibrillation (AF), for which pre-clinical and early-stage clinical data are suggestive of some degree of preferentiality to myocardial tissue ablation without damage to adjacent structures. Here in the MANIFEST-17K study we assessed the safety of PFA by studying the post-approval use of this treatment modality. Of the 116 centers performing post-approval PFA with a pentaspline catheter, data were received from 106 centers (91.4% participation) regarding 17,642 patients undergoing PFA (mean age 64, 34.7% female, 57.8% paroxysmal AF and 35.2% persistent AF). No esophageal complications, pulmonary vein stenosis or persistent phrenic palsy was reported (transient palsy was reported in 0.06% of patients; 11 of 17,642). Major complications, reported for ~1% of patients (173 of 17,642), were pericardial tamponade (0.36%; 63 of 17,642) and vascular events (0.30%; 53 of 17,642). Stroke was rare (0.12%; 22 of 17,642) and death was even rarer (0.03%; 5 of 17,642). Unexpected complications of PFA were coronary arterial spasm in 0.14% of patients (25 of 17,642) and hemolysis-related acute renal failure necessitating hemodialysis in 0.03% of patients (5 of 17,642). Taken together, these data indicate that PFA demonstrates a favorable safety profile by avoiding much of the collateral damage seen with conventional thermal ablation. PFA has the potential to be transformative for the management of patients with AF.Peer reviewe

The role of the complement system in ischemic stroke and neural plasticity

Evidence from experimental animal studies suggests that complement activation in the brain is a “double-edged sword” as it exerts beneficial or detrimental effects depending on the context. Here, we assessed whether complement activation in the systemic circulation could be a predictive biomarker of functional outcome after stroke. Further, we studied the role of the complement system in brain plasticity and recovery after ischemic stroke. We found that acute and delayed phase plasma levels of C3 and C3a differ substantially among patients suffering from ischemic stroke of different etiology, and the association of plasma C3 and C3a levels with case/control status and with functional outcome is ischemic stroke subtype-dependent. In large vessel disease and cardioembolic stroke patients, C3 levels at 3-month follow up were associated with an unfavorable functional outcome at both 3 months and 2 years after stroke. However, in cardioembolic stroke patients moderate increase in plasma C3a/C3 ratio predicted favorable outcome after 2 years (Paper I and II). Furthermore, two single nucleotide polymorphisms (SNPs) in the C3 gene were found to be associated with ischemic stroke independently of traditional risk factors and one of these SNPs was associated with cryptogenic stroke (Paper III). Also, two SNPs were associated with plasma C3a or C3 levels independently of age, sex and case/control status. Taken together, the role of the complement system in ischemic stroke is strongly dependent on stroke etiology. We have also found that C3a overexpression in mice increased, whereas C3a receptor (C3aR) deficiency decreased the number of post-stroke-born neurons in the peri-infarct cortex without affecting the infarct size. Furthermore, the density of presynaptic puncta and GAP43-positive axonal growth cones in the cortex surrounding the infarct were lower in the C3aR-deficient compared to control mice, while in the C3a-overexpressing mice post stroke axonal plasticity response was increased. Mice lacking C3aR showed a more pronounced sensorimotor functional deficit as assessed by behavioral testing (Paper IV). These results indicate that C3aR signaling should be considered as a target when designing therapeutic strategies to improve functional recovery after ischemic stroke. To study complement-related neural plasticity in a non-pathological context, we performed electrophysiological recordings in the CA1 region of live hippocampal slices of young mice lacking C3 and control mice. We found that the C3-deficient mice had a decreased neurotransmitter release probability but dendritic spine density, and frequency and amplitude of miniature excitatory postsynaptic potentials were comparable in both groups of mice. Behavioral testing using the IntelliCage platform revealed that the C3-deficient mice performed better in the place and reversal learning tasks (Paper V). These findings may have implications for the management of disorders involving synapse elimination, such as Alzheimer’s diseases, autism or multiple sclerosis

Sex differences in rate and rhythm control for atrial fibrillation

Atrial fibrillation (AF), is the most common sustained arrhythmia and is associated with a substantial increase in morbidity and mortality. Several studies have demonstrated sex-related differences in various aspects, including age at diagnosis, clinical manifestations, management and prognosis. These dissimilarities may dictate different approaches to management and could translate to differences in outcomes. However, similarly to other cardiovascular therapies, there may be a tendency to treat females more conservatively and less aggressively than male patients. The use of oral anticoagulants, for example, is lower in female patients with AF. Electrical cardioversion is less often used. Likewise, despite higher rates of adverse reactions to antiarrhythmic drugs in women, they are less likely to undergo catheter ablations, a well-established therapeutic approach to symptomatic patients with recurrences of AF. In this article, we review sex related dissimilarities in patients with AF. In addition, we discuss various treatment options, and specifically refer to differences in access of treatment, success rates, and potential treatment-related complications