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.

Inhibition of peripheral chemoreceptors improves ventilatory efficiency during exercise in heart failure with preserved ejection fraction - a role of tonic activity and acute reflex response.

Peripheral chemoreceptors (PChRs) play a significant role in maintaining adequate oxygenation in the bloodstream. PChRs functionality comprises two components: tonic activity (PChT) which regulates ventilation during normoxia and acute reflex response (peripheral chemosensitivity, PChS), which increases ventilation following a specific stimulus. There is a clear link between augmented PChS and exercise intolerance in patients with heart failure with reduced ejection fraction. It has been also shown that inhibition of PChRs leads to the improvement in exercise capacity. However, it has not been established yet: 1) whether similar mechanisms take part in heart failure with preserved ejection fraction (HFpEF) and 2) which component of PChRs functionality (PChT vs. PChS) is responsible for the benefit seen after the acute experimental blockade. To answer those questions we enrolled 12 stable patients with HFpEF. All participants underwent an assessment of PChT (attenuation of minute ventilation in response to low-dose dopamine infusion), PChS (enhancement of minute ventilation in response to hypoxia) and a symptom-limited cardiopulmonary exercise test on cycle ergometer. All tests were placebo-controlled, double-blinded and performed in a randomized order. Under resting conditions and at normoxia dopamine attenuated minute ventilation and systemic vascular resistance (p = 0.03 for both). These changes were not seen with placebo. Dopamine also decreased ventilatory and mean arterial pressure responses to hypoxia (p < 0.05 for both). Inhibition of PChRs led to a decrease in V˙E/V˙CO2 comparing to placebo (36 ± 3.6 vs. 34.3 ± 3.7, p = 0.04), with no effect on peak oxygen consumption. We found a significant relationship between PChT and the relative decrement of V˙E/V˙CO2 on dopamine comparing to placebo (R = 0.76, p = 0.005). There was a trend for correlation between PChS (on placebo) and V˙E/V˙CO2 during placebo infusion (R = 0.56, p = 0.059), but the relative improvement in V˙E/V˙CO2 was not related to the change in PChS (dopamine vs. placebo). We did not find a significant relationship between PChT and PChS. In conclusion, inhibition of PChRs in HFpEF population improves ventilatory efficiency during exercise. Increased PChS is associated with worse (higher) V˙E/V˙CO2, whereas PChT predicts an improvement in V˙E/V˙CO2 after PChRs inhibition. This results may be meaningful for patient selection in further clinical trials involving PChRs modulation.

The Role of Pharmacological Treatment in the Chemoreflex Modulation.

From a physiological point of view, peripheral chemoreceptors (PCh) are the main sensors of hypoxia in mammals and are responsible for adaptation to hypoxic conditions. Their stimulation causes hyperventilation-to increase oxygen uptake and increases sympathetic output in order to counteract hypoxia-induced vasodilatation and redistribute the oxygenated blood to critical organs. While this reaction promotes survival in acute settings it may be devastating when long-lasting. The permanent overfunctionality of PCh is one of the etiologic factors and is responsible for the progression of sympathetically-mediated diseases. Thus, the deactivation of PCh has been proposed as a treatment method for these disorders. We review here physiological background and current knowledge regarding the influence of widely prescribed medications on PCh acute and tonic activities.

Induction of Day-Time Periodic Breathing is Associated With Augmented Reflex Response From Peripheral Chemoreceptors in Male Patients With Systolic Heart Failure.

Spontaneous day-time periodic breathing (sPB) constitutes a common phenomenon in systolic heart failure (HF). However, it is unclear whether PB during wakefulness could be easily induced and what are the physiological and clinical correlates of patients with HF in whom PB induction is possible. Fifty male HF patients (age 60.8 ± 9.8 years, left ventricle ejection fraction 28.0 ± 7.4%) were prospectively screened and 46 enrolled. After exclusion of patients with sPB the remaining underwent trial of PB induction using mild hypoxia (stepwise addition of nitrogen gas to breathing mixture) which resulted in identification of inducible (iPB) in 51%. All patients underwent assessment of hypoxic ventilatory response (HVR) using transient hypoxia and of hypercapnic ventilatory response (HCVR) employing Read's rebreathing method. The induction trial did not result in any adverse events and minimal SpO2 during nitrogen administration was ∼85%. The iPB group (vs. non-inducible PB group, nPB) was characterized by greater HVR (0.90 ± 0.47 vs. 0.50 ± 0.26 L/min/%; p <0.05) but comparable HCVR (0.88 ± 0.54 vs. 0.67 ± 0.68 L/min/mmHg; p = NS) and by worse clinical and neurohormonal profile. Mean SpO2 which induced first cycle of PB was 88.9 ± 3.7%, while in sPB mean SpO2 preceding first spontaneous cycle of PB was 96.0 ± 2.5%. There was a reverse relationship between HVR and the relative variation of SpO2 during induced PB (r = -0.49, p = 0.04). In summary, PB induction is feasible and safe in HF population using simple and standardized protocol employing incremental, mild hypoxia. Pathophysiology of iPB differs from sPB, as it relies mostly on overactive peripheral chemoreceptors. At the same time enhanced HVR might play a protective role against profound hypoxia during iPB.

Contribution of Peripheral Chemoreceptors to Exercise Intolerance in Heart Failure.

Peripheral chemoreceptors (PChRs), because of their strategic localization at the bifurcation of the common carotid artery and along the aortic arch, play an important protective role against hypoxia. Stimulation of PChRs evokes hyperventilation and hypertension to maintain adequate oxygenation of critical organs. A relationship between increased sensitivity of PChRs (hyperreflexia) and exercise intolerance (ExIn) in patients with heart failure (HF) has been previously reported. Moreover, some studies employing an acute blockade of PChRs (e.g., using oxygen or opioids) demonstrated improvement in exercise capacity, suggesting that hypertonicity is also involved in the development of ExIn in HF. Nonetheless, the precise mechanisms linking dysfunctional PChRs to ExIn remain unclear. From the clinical perspective, there are two main factors limiting exercise capacity in HF patients: subjective perception of dyspnoea and muscle fatigue. Both have many determinants that might be influenced by abnormal signalling from PChRs, including: exertional hyperventilation, oscillatory ventilation, ergoreceptor oversensitivity, and augmented sympathetic tone. The latter results in reduced muscle perfusion and altered muscle structure. In this review, we intend to present the milieu of abnormalities tied to malfunctioning PChRs and discuss their role in the complex relationships leading, ultimately, to ExIn.

Acute hyperoxia reveals tonic influence of peripheral chemoreceptors on systemic vascular resistance in heart failure patients.

Peripheral chemoreceptors' (PCh) hyperactivity increases sympathetic tone. An augmented acute ventilatory response to hypoxia, being a marker of PCh oversensitivity, was also identified as a marker of poor prognosis in HF. However, not much is known about the tonic (chronic) influence of PCh on cardio-respiratory parameters. In our study 30 HF patients and 30 healthy individuals were exposed to 100% oxygen for 1 min during which minute ventilation and hemodynamic parameters were non-invasively recorded. Systemic vascular resistance (SVR) and mean arterial pressure (MAP) responses to acute hyperoxia differed substantially between HF and control. In HF hyperoxia caused a significant drop in SVR in early stages with subsequent normalization, while increase in SVR was observed in controls. MAP increased in controls, but remained unchanged in HF. Bilateral carotid bodies excision performed in two HF subjects changed the response to hyperoxia towards the course seen in healthy individuals. These differences may be explained by the domination of early vascular reaction to hyperoxia in HF by vasodilation due to the inhibition of augmented tonic activity of PCh. Otherwise, in healthy subjects the vasoconstrictive action of oxygen remains unopposed. The magnitude of SVR change during acute hyperoxia may be used as a novel method for tonic PCh activity assessment.

Neck Chamber Technique Revisited: Low-Noise Device Delivering Negative and Positive Pressure and Enabling Concomitant Carotid Artery Imaging With Ultrasonography.

Background and Objectives: Recently, novel noiseless device for the assessment of baroreceptor function with the neck suction (NS) has been presented. In this study, we present another in-house approach to the variable-pressure neck chamber method. Our device offers further critical improvements. First, it enables delivery of negative (NS) as well as positive pressure (neck pressurizing, NP) in a noiseless manner. Second, we used small, 3D-printed cups positioned over the carotid sinuses instead of cumbersome neck collar to improve subject comfort and to test feasibility of tracking the pressure-induced changes in carotid artery with ultrasonography. Methods: Five healthy, non-smoking, normal-weight subjects aged 29 ± 3 years (mean ± SD) volunteered for the study. Heart rate (HR, bpm) and mean arterial pressure (MAP, mmHg) responses to short, 7-s long episodes of NS and NP were recorded. Each trial consisted of 12 episodes of variable-pressure: six episodes of NS (suction ranging between -10 and -80 mmHg) and six episodes of NP (pressure ranging between + 10 and + 80 mmHg). Carotid artery sonography was performed during the NS and NP in four subjects, on another occasion. Results: The variable-pressure episodes resulted consistently in the expected pattern of hemodynamic alterations: HR and MAP increases or decreases following the NP and NS, respectively, as evidenced by the coefficient of determination (R2) of ≥0.78 for the carotid-HR response curve (for all five participants) and the carotid-MAP response curve (for four out of five participants; the curve cannot be calculated for one subject). We found a linear, dose-dependent relation between the applied pressure and the systolic-diastolic difference in carotid artery diameter. Conclusion: The novel device enables noiseless stimulation and unloading of the carotid baroreceptors with the negative and positive pressure, respectively, applied on the subject's neck via small, asymmetric and one-side flattened, 3D-printed cups. The unique design of the cups enables concomitant visualizing of the carotid artery during the NS or NP administration, and thereby direct monitoring of the intensity of mechanical stimulus targeting the carotid baroreceptors.

Antiplatelets in acute coronary syndrome in Poland - from guidelines to clinical practice.

Acute coronary syndrome is a factor for poor prognosis and recurrent cardiovascular events. Adequate antiplatelet therapy is crucial in patients with the acute coronary syndrome for risk reduction. Such treatment is well described in four documents issued by the European Society of Cardiology, which precisely illustrate the use of antiplatelets in the settings of ST-elevated and non-ST elevated myocardial infarction. Despite its unquestioned role in the treatment of acute coronary syndrome, recent real-world-data from Polish registries reveal poor adherence to the guidelines-recommended antiplatelet treatment in Poland. Thus, we present here a comprehensive review of the use of antiplatelets in the settings of the acute coronary syndrome. Each phase of the treatment, i.e. pre-hospital, in-hospital and post-hospital, is discussed separately for a better understanding of the decision-making process at each step. We also present unpublished data from Polish registries (e.g. PL-ACS 2019, National Registry of Procedures of Invasive Cardiology, RECEPTOmetrPEX panel) regarding adherence to the guidelines-recommended treatment in Poland, thus highlighting the points of care which should be immediately improved. It has to be stressed here that careful assessment of ischaemic and bleeding risk has to be performed in each patient with acute coronary syndrome individually and repeated at successive phases of the treatment. Only such an approach allows for appropriate antiplatelet therapy tailoring.

Utilization of Subcutaneous Cardioverter-Defibrillator in Poland and Europe-Comparison of the Results of Multi-Center Registries.

The implantation of a subcutaneous cardioverter-defibrillator (S-ICD) may be used instead of a traditional transvenous system to prevent sudden cardiac death. Our aim was to compare the characteristics of S-ICD patients from the multi-center registry of S-ICD implantations in Poland with the published results of the European Snapshot Survey on S-ICD Implantation (ESSS-SICDI). We compared data of 137 Polish S-ICD patients with 68 patients from the ESSS-SICDI registry. The groups did not differ significantly in terms of sex, prevalence of ischemic cardiomyopathy, concomitant diseases, and the rate of primary prevention indication. Polish patients had more advanced heart failure (New York Heart Association (NYHA) class III: 11.7% vs. 2.9%, NYHA II: 48.9% vs. 29.4%, NYHA I: 39.4% vs. 67.7%, p < 0.05 each). Young age (75.9% vs. 50%, p < 0.05) and no vascular access (7.3% vs. 0%, p < 0.05) were more often indications for S-ICD. The percentage of patients after transvenous system removal due to infections was significantly higher in the Polish group (11% vs. 1.5%, p < 0.05). In the European population, S-ICD was more frequently chosen because of patients' active lifestyle and patients' preference (both 10.3% vs. 0%, p < 0.05). Our analysis shows that in Poland, compared to other European countries, subcutaneous cardioverters-defibrillators are being implanted in patients at a more advanced stage of chronic heart failure. The most frequent reason for choosing a subcutaneous system instead of a transvenous ICD is the young age of a patient.

Oxygenation pattern and compensatory responses to hypoxia and hypercapnia following bilateral carotid body resection in humans.

KEY POINTS: Five years after bilateral carotid body resection (bCBR) performed in four patients, the absence of the hypoxic ventilatory response persisted, suggesting no compensatory regrowth. Breathing hypoxic gas mixtures (15% and 12%) results in a lower (by ∼10%) minimal blood oxygen saturation ( SpO2 ) in bCBR patients compared to heart failure subjects (CHF) with intact peripheral chemoreceptors. After bCBR, patients were characterized by a greater short-term variability in SpO2 during mild hypoxia in comparison to the CHF group. The ventilatory response to hypercapnia was preserved following bCBR and was sufficient to maintain minimal SpO2 at levels comparable to controls when combined with hypoxia. Bilateral CBR - a novel treatment modality for sympathetically mediated diseases - should be used with caution due to the risk of significant desaturation even during mild hypoxia equivalent to that experienced during long-haul air travel and high altitude. ABSTRACT: Carotid body resection has been proposed as a novel treatment for sympathetically mediated diseases but the safety of bilateral carotid body resection (bCBR) for blood oxygenation during hypoxic stress (long-haul flights or high altitude) remains uncertain. Also unknown is whether central ventilatory drive is sufficient to maintain adequate oxygen saturation when exposed to hypercapnia with concomitant hypoxia. Thus, we administered: 15% O2 , 12% O2 , 5% CO2 /12% O2 and 5% CO2 /95% O2 to a group of four patients with congestive heart failure (65 ± 2.9 years) in whom bCBR was performed 5 years earlier. Ventilatory, haemodynamic and blood oxygen saturation ( SpO2 ) responses were recorded non-invasively and compared to control groups with intact peripheral chemoreceptors (both healthy and heart failure patients). First, we confirmed that the ventilatory response to hypoxia was eliminated in patients with bCBR, although the increase in cardiac output was preserved. Second, administration of hypoxic gas mixtures resulted in a larger decrease in SpO2 and greater short-term variability of the SpO2 leading to a lower minimal SpO2 for both hypoxia levels in the bCBR group compared to heart failure controls (82.5 ± 1.2% vs. 91.6 ± 2.3% for 15% O2 and 73.8 ± 4.0% vs. 83.7 ± 3.1% for 12% O2 ). Third, in bCBR patients the ventilatory response to hypercapnia was present and sufficient to maintain a minimal SpO2 at a level comparable to heart failure controls following administration of 5% CO2 /12% O2 (88.7 ± 4.2% vs. 91.1 ± 2.8%). We conclude that bCBR carries a risk of significant oxygen desaturation even during mild hypoxia. Despite preservation of central chemosensitivity, future studies should focus on unilateral CBR or on pharmacological modulation of peripheral chemosensitivity.

Frailty and cognitive impairment are predictive of takotsubo syndrome following pacemaker implantation.

BACKGROUND: Pacemaker (PM) implantation may cause acute emotional distress leading to takotsubo syndrome (TTS). Frailty and cognitive impairment are known to influence outcomes after surgical procedures. It is unclear whether they may also predispose to TTS following PM implantation. METHODS: We identified nine cases (81 ± 6 years) of TTS following PM implantation that took place between 2013 and 2017 in one high volume implantation center. TTS was diagnosed based on typical echocardiographic appearance with resolution over time and (in cases where deemed necessary) normal coronary angiography. The TTS cases were compared with 30 consecutive cases of PM implantation (75 ± 9 years), which were not complicated by TTS (control group). Frailty was assessed using retrospective Risk Analysis Index (RAI-A). Pacing parameters were analyzed during PM implantation and after 1 month. RESULTS: Cognitive impairment was more prevalent (67% vs 10%, P = .0005), and RAI-A index was significantly higher in the TTS group compared to the control group (26 ± 13.7 vs 13.1 ± 9.8, P = .008). Perioperative right ventricular threshold was significantly higher in patients with TTS comparing to controls (0.99 ± 0.43 V vs 0.74 ± 0.20 V, P = .04). The magnitude of decrease in right ventricular threshold between implantation and 1 month follow-up was greater in TTS patients compared to controls (-0.41 ± 0.29 V vs -0.15 ± 0.38 V, P = .049). CONCLUSIONS: TTS is a rare complication of PM implantation. Patients with cognitive impairment and frailty are at risk of TTS. Right ventricular pacing threshold is acutely affected by TTS and improves over time.

Seat belts-related behaviors in car drivers with cardiac implantable electronic devices.

BACKGROUND: Seat belt use is the single most effective means of reducing fatal injuries in road traffic accidents. The presence of a cardiac implantable electronic device (CIED) might influence seat belt-related behaviors due to the physical proximity of the seat belt and left subclavian area in which the device is usually implanted. Understanding the underlying mechanisms of improper seat belt use may improve safety of these patients. METHODS: We performed a prospective study using a structured questionnaire with 120 CIED recipients (age, 63.9 ± 10.9 years) attending a pacing outpatient clinic. All study participants were active drivers and predominantly male. The majority of patients (79%) had undergone high-energy device implantation. RESULTS: We found that 18% of study participants do not fasten seat belts on a regular basis or use the seat belt in an atypical fashion (such as under the armpit). Moderate or high level of discomfort from the interaction between seat belt and CIED was present in 27%, while more than half (51%) were afraid of seat belt-induced CIED damage. In multifactorial analysis, we found the following independent predictors of improper seat belt use: (1) at least moderate level of discomfort at the CIED site (P = 0.02); (2) fear of CIED damage (P = 0.009); and (3) irregular seat belt use prior to CIED implantation (P = 0.037). CONCLUSIONS: Improper seat belt-related behaviors are common in CIED recipients. They arise from previous habits and from CIED-related physical and psychological factors. Patients' education regarding the importance and safety of proper seat belt use is a priority.

Hypoxic tachycardia is not a result of increased respiratory activity in healthy subjects.

NEW FINDINGS: What is the central question of this research? Does increased ventilation contribute to the increase in heart rate during transient exposure to hypoxia in humans? What is the main finding and its importance? Voluntary suppression of the ventilatory response to transient hypoxia does not affect the magnitude of the heart rate response to the stimulus. This indicates that hypoxic tachycardia is not secondary to hyperpnoea in humans. Better understanding of the physiology underlying the cardiovascular response to hypoxia might help in identification of new markers of elevated chemoreceptor activity, which has been proposed as a target in treatment of sympathetically mediated diseases. ABSTRACT: Animal data suggest that hypoxic tachycardia is secondary to hyperpnoea, and for years this observation has been extrapolated to humans, despite a lack of experimental evidence. We addressed this issue in 17 volunteers aged 29 ± 7 (SD) years. A transient hypoxia test, comprising several nitrogen-breathing episodes, was performed twice in each subject. In the first test, the subject breathed spontaneously (spontaneous breathing). In the second test, the subject was repeatedly asked to adjust his or her depth and rate of breathing according to visual (real-time inspiratory flow) and auditory (metronome sound) cues, respectively (controlled breathing), to maintain respiration at the resting level during nitrogen-breathing episodes. Hypoxic responsiveness, including minute ventilation [Hyp-VI; in liters per minute per percentage of blood oxygen saturation ( SpO2 )], tidal volume [Hyp-VT; in litres per SpO2 ], heart rate [Hyp-HR; in beats per minute per SpO2 ], systolic [Hyp-SBP; in millimetres of mercury per SpO2 ] and mean blood pressure [Hyp-MAP; in millimetres of mercury per SpO2 ] and systemic vascular resistance [Hyp-SVR; in dynes seconds (centimetres)-5 per SpO2 ] was calculated as the slope of the regression line relating the variable to SpO2 , including pre- and post-hypoxic values. The Hyp-VI and Hyp-VT were reduced by 69 ± 25 and 75 ± 10%, respectively, in controlled versus spontaneous breathing (Hyp-VI, -0.30 ± 0.15 versus -0.11 ± 0.09; Hyp-VT, -0.030 ± 0.024 versus -0.007 ± 0.004; both P < 0.001). However, the cardiovascular responses did not differ between spontaneous and controlled breathing (Hyp-HR, -0.62 ± 0.24 versus -0.71 ± 0.33; Hyp-MAP, -0.43 ± 0.19 versus -0.47 ± 0.21; Hyp-SVR, 9.15 ± 5.22 versus 9.53 ± 5.57; all P ≥ 0.22), indicating that hypoxic tachycardia is not secondary to hyperpnoea. Hyp-HR was correlated with Hyp-SVR (r = -074 and -0.80 for spontaneous and controlled breathing, respectively; both P < 0.05) and resting barosensitivity assessed with the sequence technique (r = -0.60 for spontaneous breathing; P < 0.05). This might suggest that the baroreflex mechanism is involved.

Human carotid bodies as a therapeutic target: new insights from a clinician's perspective.

From the physiological point of view, carotid bodies are mainly responsible for the ventilatory response to hypoxia; however, they also take part in the regulation of sympathetic tone. According to preclinical data, these structures likely contribute to the development and progression of sympathetically mediated diseases. Moreover, carotid body deactivation in animal models improved blood pressure control in hypertension and reduced mortality in heart failure, along with reducing sympathetic activity. On this basis, two first-in-man studies have been recently performed to investigate the safety and feasibility of such an approach in humans. In this review we summarise the current knowledge regarding the function of carotid bodies, the prevalence of their abnormalities, and the consequences of their excision in human hypertension and heart failure.

Carotid body resection for sympathetic modulation in systolic heart failure: results from first-in-man study.

AIMS: Augmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CBs), characterize patients with systolic heart failure and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CBs in these patients can be performed safely to decrease sympathetic tone. METHODS AND RESULTS: We studied 10 male patients with systolic heart failure (age, 59 ± 3 years; LVEF, 27 ± 7%) who underwent unilateral right-sided CB resection (four patients) or bilateral CB resection (six patients). Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post-CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post-procedure and adverse events assessed up to 12 months. At the 1-month visit, CB resection was associated with a significant decrease both in MSNA (86.6 ± 3.1 vs. 79.7 ± 4.2 bursts/100 beats, P = 0.03) and in peripheral chemosensitivity (1.35 ± 0.19 vs. 0.41 ± 0.17 L/min/SpO2 , P = 0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection, there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non-invasive ventilation. CONCLUSION: We present first-in-man evidence that CB resection in patients with systolic heart failure is associated with a decrease in sympathetic activity. A bilateral procedure may carry a risk of worsening oxygenation at night. CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.

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.