The effects of P2Y12 adenosine receptors' inhibitors on central and peripheral chemoreflexes.

Introduction: The most common side effect of ticagrelor is dyspnea, which leads to premature withdrawal of this life-saving medication in 6.5% of patients. Increased chemoreceptors' sensitivity was suggested as a possible pathophysiological explanation of this phenomenon; however, the link between oversensitization of peripheral and/or central chemosensory areas and ticagrelor intake has not been conclusively proved. Methods: We measured peripheral chemoreceptors' sensitivity using hypoxic ventilatory response (HVR), central chemoreceptors' sensitivity using hypercapnic hyperoxic ventilatory response (HCVR), and dyspnea severity before and 4 ± 1 weeks following ticagrelor initiation in 11 subjects with chronic coronary syndrome undergoing percutaneous coronary intervention (PCI). The same tests were performed in 11 age-, sex-, and BMI-matched patients treated with clopidogrel. The study is registered at ClinicalTrials.com at NCT05080478. Results: Ticagrelor significantly increased both HVR (0.52 ± 0.46 vs. 0.84 ± 0.69 L min-1 %-1; p < 0.01) and HCVR (1.05 ± 0.64 vs. 1.75 ± 1.04 L min-1 mmHg-1; p < 0.01). The absolute change in HVR correlated with the change in HCVR. Clopidogrel administration did not significantly influence HVR (0.63 ± 0.32 vs. 0.58 ± 0.33 L min-1%-1; p = 0.53) and HCVR (1.22 ± 0.67 vs. 1.2 ± 0.64 L min-1 mmHg-1; p = 0.79). Drug-related dyspnea was reported by three subjects in the ticagrelor group and by none in the clopidogrel group. These patients were characterized by either high baseline HVR and HCVR or excessive increase in HVR following ticagrelor initiation. Discussion: Ticagrelor, contrary to clopidogrel, sensitizes both peripheral and central facets of chemodetection. Two potential mechanisms of ticagrelor-induced dyspnea have been identified: 1) high baseline HVR and HCVR or 2) excessive increase in HVR or HVR and HCVR. Whether other patterns of changes in chemosensitivities play a role in the pathogenesis of this phenomenon needs to be further investigated.

Effectiveness of screening for atrial fibrillation and its determinants. A meta-analysis.

BACKGROUND: Many atrial fibrillation patients eligible for oral anticoagulants are unaware of the presence of AF, and improved detection is necessary to facilitate thromboprophylaxis against stroke. OBJECTIVE: To assess the effectiveness of screening for AF compared to no screening and to compare efficacy outcomes of different screening strategies. MATERIALS AND METHODS: Cochrane Central Register of Controlled Trials, EMBASE and MEDLINE from Jan 1, 2000 -Dec 31, 2015 were searched. Studies employing systematic or opportunistic screening and using ECG or pulse palpation in populations age ≥40 years were included. Data describing study and patient characteristics and number of patients with new AF were extracted. The outcome was the incidence of previously undiagnosed AF. RESULTS: We identified 25 unique (3 RCTs and 22 observational) studies (n = 88 786) from 14 countries. The incidence of newly detected AF due to screening was 1.5% (95% CI 1.1 to 1.8%). Systematic screening was more effective than opportunistic: 1.8% (95% CI 1.4 to 2.3%) vs. 1.1% (95% CI 0.6 to 1.6%), p<0.05, GP-led screening than community based: 1.9% (95% CI 1.4 to 2.4%) vs. 1.1% (95% CI 0.7 to 1.6%), p<0.05, and repeated heart rhythm measurements than isolated assessments of rhythm: 2.1% (95% CI 1.5-2.8) vs. 1.2% (95% CI 0.8-1.6), p<0.05. Only heart rhythm measurement frequency had statistical significance in a multivariate meta-regression model (p<0.05). CONCLUSIONS: Active screening for AF, whether systematic or opportunistic, is effective beginning from 40 years of age. The organisation of screening process may be more important than technical solutions used for heart rhythm assessment.

[Patient with the intervention of an implantable cardioverter-defibrillator in a hospital emergency department].

OBJECTIVE: Introduction: Implantable cardioverter-defibrillators (ICD) improve prognosis in patients with malignant ventricular arrhythmias. Patients with ICD represent a significant proportion of all Emergency Department (ED) admissions. The number of these visits due to the high-energy therapy or antitachycardia pacing (ATP) delivered by the implanted cardioverter-defibrillator is constantly increasing. The aim: To present the prevalence and type of therapeutic interventions of an ICD in patients admitted to ED in 2014-2017 at two medical centers covering approx. 400 000 residents. PATIENTS AND METHODS: Materials and methods: The patients' documentation was analyzed to find patients admitted to emergency department because of the suspicion of the ventricular arrhythmias' therapy delivered by ICD. RESULTS: Results: In most cases adequate high-energy therapies due to life-threatening ventricular arrhythmias were the reason for hospitalization. We identified 126 patients aged 63.0±12.0 years, 108 (86&) of male and 18 (14&) of female. Among 171 ED admissions 6 were associated with ATP and 149 with high-energy therapy, 10 cases presented with VT without therapies, 5 with fantom shocks and in one case the patient had only a pacemaker but not ICD. The number of ICD shocks ranged from 1 to 108. Inadequate ICD discharges were found in 26 (17.4&) of high energy therapies. CONCLUSION: Conclusions:1. The number of patients with ICD admitted to Emergency Department due to the initiation of high-energy or anti-tachyarrhythmic therapy has been steadily increasing in recent years. 2. In most cases, the reason for the admissions are adequate high-energy therapies, i.e. ICD discharges that disrupt the potentially life threatening arrhythmia. 3. Accurate medical history, the possibility of assessing the heart rate stored in the ICD memory during its intervention form the basis for establishing a plan of action in patients with ICD.

Effects of selective carotid body stimulation with adenosine in conscious humans.

KEY POINTS: In humans, excitation of peripheral chemoreceptors with systemic hypoxia causes hyperventilation, hypertension and tachycardia. However, the contribution of particular chemosensory areas (carotid vs. aortic bodies) to this response is unclear. We showed that selective stimulation of the carotid body by the injection of adenosine into the carotid artery causes a dose-dependent increase in minute ventilation and blood pressure with a concomitant decrease in heart rate in conscious humans. The ventilatory response was abolished and the haemodynamic response was diminished following carotid body ablation. We found that the magnitude of adenosine evoked responses in minute ventilation and blood pressure was analogous to the responses evoked by hypoxia. By contrast, opposing heart rate responses were evoked by adenosine (bradycardia) vs. hypoxia (tachycardia). Intra-carotid adenosine administration may provide a novel method for perioperative assessment of the effectiveness of carotid body ablation, which has been recently proposed as a treatment strategy for sympathetically-mediated diseases. ABSTRACT: Stimulation of peripheral chemoreceptors by acute hypoxia causes an increase in minute ventilation (VI), heart rate (HR) and arterial blood pressure (BP). However, the contribution of particular chemosensory areas, such as carotid (CB) vs. aortic bodies, to this response in humans remains unknown. We performed a blinded, randomized and placebo-controlled study in 11 conscious patients (nine men, two women) undergoing common carotid artery angiography. Doses of adenosine ranging from 4 to 512 µg or placebo solution of a matching volume were administered in randomized order via a diagnostic catheter located in a common carotid artery. Separately, ventilatory and haemodynamic responses to systemic hypoxia were also assessed. Direct excitation of a CB with intra-arterial adenosine increased VI, systolic BP, mean BP and decreased HR. No responses in these variables were seen after injections of placebo. The magnitude of the ventilatory and haemodynamic responses depended on both the dose of adenosine used and on the level of chemosensitivity as determined by the ventilatory response to hypoxia. Percutaneous radiofrequency ablation of the CB abolished the adenosine evoked respiratory response and partially depressed the cardiovascular response in one participant. The results of the present study confirm the excitatory role of purines in CB physiology in humans and suggest that adenosine may be used for selective stimulation and assessment of CB activity. The trial is registered at ClinicalTrials.gov NCT01939912.

Late Cardiac Tamponade as a Result of Parietal Pericardium Erosion.

Late onset cardiac tamponade is a rare and particularly challenging (both from diagnostic and management perspectives) complication of intracardiac lead implantation. We present a case of a late tamponade leading to cardiogenic shock, which occurred 1,164 days after implantable cardioverter-defibrillator (ICD) implantation. Open repair revealed unusual and, to our knowledge, not yet reported mechanism of the disease. A pressure sore caused by an ICD lead was found in the parietal layer of pericardium with no visible damage to the visceral layer. Conservative management in the described clinical scenario could be fatal, thus awareness of this pathomechanism of tamponade is critical.

[Current opinions on clinical significance of carotid bodies]. / Obecne poglady na temat znaczenia klinicznego klebków szyjnych.

Carotid body (lat. glomus caroticum) is a small structure of the size of maximally 7 mm of height and 4 mm of diameter and 2 mm of thickness located bilaterally and posteriorly to bifurcation of the carotid artery into internal and external carotid artery. It is a cluster of chemoreceptors detecting changes in the composition of arterial blood flowing through it. Recent research studies show that significance of its function may be greater than it has been previously established in the aspect of cardiology and oncology. Currently, in cardiology journals the high concern is devoted to the influence of chronically increased activity of carotid bodies on the progression of heart failure. In oncology it has been found that carotid body paraganglioma originating from carotid body known also as chemodectoma is the most common paraganglioma in the region of head and neck. In the authors' opinion it seems reasonable to gather the novel data on carotid bodies and to conduct research studies in order to make methods of determination of their morphology and function more perfect. In the present study a summary of the up-to-date knowledge on carotid bodies as well as on their pathophysiology and physiology has been made.