Piotr Niewiński

Carotid body removal for treatment of chronic systolic heart failure

BACKGROUND Augmented reflex response from peripheral chemoreceptors characterises chronic heart failure (CHF), contributes to autonomic imbalance and exercise intolerance and predicts poor outcome. METHODS AND RESULTS We present a case of a 56-year-old male patient with ischaemic CHF, who underwent surgical, unilateral carotid body resection to reduce peripheral chemosensitivity. At 2-month and 6-month follow-ups, we document a persistent decrease in peripheral chemosensitivity accompanied by an improvement in exercise capacity, sleep disordered breathing and quality of life. Autonomic balance was favourably affected as evidenced by improved heart rate variability and augmented cardiac baroreflex sensitivity. There were no procedure-related adverse events. CONCLUSIONS Denervation of a carotid body may offer a clinical strategy to restore autonomic balance and improve morbidity in heart failure (NCT01653821).

Dissociation between blood pressure and heart rate response to hypoxia after bilateral carotid body removal in men with systolic heart failure

What is the central question of this study? Carotid body denervation removes the ventilatory response to acute hypoxia, although haemodynamic responses to acute hypoxia after carotid body removal have not been described conclusively in humans. What is the main finding and its importance? Carotid body removal results in dissociation of heart rate and blood pressure responses to hypoxia in human subjects. While the heart rate response (tachycardia) is maintained, there is a significant attenuation of the blood pressure response (hypertension), which indicates the existence of different sensory afferent pathways in the haemodynamic response to hypoxia that has important clinical implications for this novel therapeutic modality.

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

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.

Consequences of peripheral chemoreflex inhibition with low‐dose dopamine in humans

Low‐dose dopamine reduces the ventilatory response to acute hypoxia both in animal and in human studies. In this study we show that low‐dose dopamine also attenuates the haemodynamic responses (tachycardia, hypertension) to acute hypoxia in healthy humans. Moreover, we found that dopamine withdrawal results in a temporary increase in minute ventilation. The magnitude of the increase in minute ventilation after dopamine withdrawal correlates with the degree of ventilatory response to acute hypoxia and depends on the duration of dopamine administration. Dopamine may provide a novel method for assessing differences in the level of peripheral chemoreceptor activity, which has important clinical implications given the recently reported pathological role of the carotid body in cardiovascular diseases in animals and humans.

Effects of selective carotid body stimulation with adenosine in conscious humans

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.

Carotid body modulation in systolic heart failure from the clinical perspective.

Augmented sensitivity of peripheral chemoreceptors (PChS) is a common finding in systolic heart failure (HF). It is related to lower left ventricle systolic function, higher plasma concentrations of natriuretic peptides, worse exercise tolerance and greater prevalence of atrial fibrillation compared to patients with normal PChS. The magnitude of ventilatory response to the activation of peripheral chemoreceptors is proportional to the level of heart rate (tachycardia) and blood pressure (hypertension) responses. All these responses can be measured non‐invasively in a safe and reproducible fashion using different methods employing either hypoxia or hypercapnia. Current interventions aimed at modulation of peripheral chemoreceptors in HF are focused on carotid bodies (CBs). There is a clear link between afferent signalling from CBs and sympathetic overactivity, which remains the priority target of modern HF treatment. However, CB modulation therapies may face several potential obstacles: (1) As evidenced by HF trials, an excessive inhibition of sympathetic system may be harmful. (2) Proximity of critical anatomical structures (important vessels and nerves) makes surgical and transcutaneous interventions on CB technically demanding. (3) Co‐existence of atherosclerosis in the area of carotid artery bifurcation increases the risk of central embolic events related to CB modulation. (4) The relative contribution of CBs vs. aortic bodies to sympathetic activation in HF patients is unclear. (5) Choosing optimal candidates for CB modulation from the population of HF patients may be problematic. (6) There is a risk of nocturnal hypoxia following CB ablation – mostly after bilateral procedures and in patients with concomitant obstructive sleep apnoea.

Assessment of baroreflex sensitivity has no prognostic value in contemporary, optimally managed patients with mild‐to‐moderate heart failure with reduced ejection fraction: a retrospective analysis of 5‐year survival

We evaluated the prognostic value of cardiac baroreflex sensitivity (BRS) in contemporary, optimally treated patients with mild‐to‐moderate heart failure with reduced ejection fraction (HFrEF).

Central Chemoreceptor Sensitivity Is Not Enhanced in Contemporary Patients With Chronic Systolic Heart Failure Receiving Optimal Treatment

BACKGROUND Clinical and prognostic consequences of enhanced central chemosensitivity in the contemporary optimally treated patients with chronic heart failure (CHF) are unknown. METHODS AND RESULTS We studied central chemosensitivity (defined as hypercapnic ventilatory response [HCVR; L/min/mmHg]) in 161 CHF patients (mean left ventricular ejection fraction [LVEF] 31 ± 6%, all receiving a combination of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker and beta-blocker) and 55 sex- and age-matched healthy controls. HCVR did not differ between CHF patients and controls (median 0.63 vs 0.57 L/min-1/mmHg-1, P = .76). When the CHF patients were divided into tertiles according to their HCVR values, there were no significant differences in clinical characteristics (except for ischemic etiology, which was more frequent in those with the highest HCVR), results of the cardiopulmonary exercise testing, and indices of heart rate variability. During the follow-up (median 28 months, range 1-48 months, ≥15 months in all survivors), 21 patients died. HCVR was not related to survival in the Cox proportional hazards analysis. CONCLUSIONS Central chemosensitivity is not enhanced in contemporary, optimally treated CHF patients and its assessment does not provide significant clinical or prognostic information.

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.

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