Feasibility and physiological effects of prone positioning in non-intubated patients with acute respiratory failure due to COVID-19 (PRON-COVID): a prospective cohort study.

BACKGROUND: The COVID-19 pandemic is challenging advanced health systems, which are dealing with an overwhelming number of patients in need of intensive care for respiratory failure, often requiring intubation. Prone positioning in intubated patients is known to reduce mortality in moderate-to-severe acute respiratory distress syndrome. We aimed to investigate feasibility and effect on gas exchange of prone positioning in awake, non-intubated patients with COVID-19-related pneumonia. METHODS: In this prospective, feasibility, cohort study, patients aged 18-75 years with a confirmed diagnosis of COVID-19-related pneumonia receiving supplemental oxygen or non-invasive continuous positive airway pressure were recruited from San Gerardo Hospital, Monza, Italy. We collected baseline data on demographics, anthropometrics, arterial blood gas, and ventilation parameters. After baseline data collection, patients were helped into the prone position, which was maintained for a minimum duration of 3 h. Clinical data were re-collected 10 min after prone positioning and 1 h after returning to the supine position. The main study outcome was the variation in oxygenation (partial pressure of oxygen [PaO2]/fractional concentration of oxygen in inspired air [FiO2]) between baseline and resupination, as an index of pulmonary recruitment. This study is registered on ClinicalTrials.gov, NCT04365959, and is now complete. FINDINGS: Between March 20 and April 9, 2020, we enrolled 56 patients, of whom 44 (79%) were male; the mean age was 57·4 years (SD 7·4) and the mean BMI was 27·5 kg/m2 (3·7). Prone positioning was feasible (ie, maintained for at least 3 h) in 47 patients (83·9% [95% CI 71·7 to 92·4]). Oxygenation substantially improved from supine to prone positioning (PaO2/FiO2 ratio 180·5 mm Hg [SD 76·6] in supine position vs 285·5 mm Hg [112·9] in prone position; p<0·0001). After resupination, improved oxygenation was maintained in 23 patients (50·0% [95% CI 34·9-65·1]; ie, responders); however, this improvement was on average not significant compared with before prone positioning (PaO2/FiO2 ratio 192·9 mm Hg [100·9] 1 h after resupination; p=0·29). Patients who maintained increased oxygenation had increased levels of inflammatory markers (C-reactive protein: 12·7 mg/L [SD 6·9] in responders vs 8·4 mg/L [6·2] in non-responders; and platelets: 241·1 × 103/µL [101·9] vs 319·8 × 103/µL [120·6]) and shorter time between admission to hospital and prone positioning (2·7 days [SD 2·1] in responders vs 4·6 days [3·7] in non-responders) than did those for whom improved oxygenation was not maintained. 13 (28%) of 46 patients were eventually intubated, seven (30%) of 23 responders and six (26%) of 23 non-responders (p=0·74). Five patients died during follow-up due to underlying disease, unrelated to study procedure. INTERPRETATION: Prone positioning was feasible and effective in rapidly ameliorating blood oxygenation in awake patients with COVID-19-related pneumonia requiring oxygen supplementation. The effect was maintained after resupination in half of the patients. Further studies are warranted to ascertain the potential benefit of this technique in improving final respiratory and global outcomes. FUNDING: University of Milan-Bicocca.

DWI/FLAIR Mismatch during Hyperacute Infarction of the Percheron Artery: Time Is Thalamus!

The artery of Percheron (AOP) is a single dominant thalamo-perforating artery that supplies bilaterally the medial thalami with variable contribution to the rostral midbrain. Occlusion of the AOP causes indeed variable and unspecific clinical symptoms due to this complex anatomy, and very often this diagnosis is delayed with the impossibility of recurring to intravenous thrombolysis (rTPA). Here, we report a case of AOP stroke that received a prompt diagnosis and therapy, owing to the availability of MR brain scan, showing a DWI/FLAIR mismatch typical of hyperacute infarctions. This case points out the importance of a high level of suspicion of AOP stroke, together with the correct implementation of imaging studies.

Effects of chronic carotid baroreceptor activation on arterial stiffness in severe heart failure.

BACKGROUND: Heart failure with reduced ejection fraction (HFrEF) is characterized by activation of the sympathetic nervous system and increased arterial stiffness, leading to an impaired ventricular-vascular coupling. Baroreflex activation therapy (BAT) has been shown to reduce muscle sympathetic nerve activity (MSNA) and improve clinical status of patients with HFrEF. The purpose of this investigation was to determine the effects of BAT on arterial stiffness in HFrEF. METHODS AND RESULTS: MSNA, clinical variables, and parameters of central blood pressure (BP) and arterial stiffness were collected in 18 NYHA Class III HFrEF patients, nine receiving BAT and nine continuing with optimal medical management alone. Patients were followed for 3 months, with measurements at that time compared to baseline evaluation. Baseline characteristics of the groups were well matched. At 3 months, BAT did not improve central BP and arterial stiffness despite a significant amelioration of MSNA, NYHA class, Minnesota living with heart failure questionnaire score, number of heart failure medications and six-minute walking distance. The control group exhibited no significant changes in all the measured variables. CONCLUSIONS: Despite significant reductions in MSNA and clinical improvement, BAT does not appear to chronically modify arterial stiffness within this HFrEF cohort. Additional study is required to determine if this result applies to the HFrEF population as a whole.

Sympathetic nerve traffic and baroreflex function in optimal, normal, and high-normal blood pressure states.

OBJECTIVE: Adrenergic activation and baroreflex dysfunction are common in established essential hypertension, elderly hypertension, masked and white-coat hypertension, resistant hypertension, and obesity-related hypertension. Whether this autonomic behavior is peculiar to established hypertension or is also detectable in the earlier clinical phases of the disease, that is, the high-normal blood pressure (BP) state, is still largely undefined, however. METHODS: In 24 individuals with optimal BP (age: 37.1  ±  2.1 years, mean  ±  SEM) and in 27 with normal BP and 38 with high-normal BP, age matched with optimal BP, we measured clinic, 24-h and beat-to-beat BP, heart rate (HR), and muscle sympathetic nerve activity (MSNA) at rest and during baroreceptor stimulation and deactivation. Measurements also included anthropometric as well as echocardiographic and homeostasis model assessment (HOMA) index. RESULTS: For similar anthropometric values, clinic, 24-h ambulatory, and beat-to-beat BPs were significantly greater in normal BP than in optimal BP. This was the case when the high-normal BP group was compared to the normal and optimal BP groups. MSNA (but not HR) was also significantly greater in high-normal BP than in normal BP and optimal BP (51.3  ±â€Š 2.0 vs. 40.3  ±  2.3 and 41.1 ±â€Š2.6  bursts per 100  heartbeats, respectively, P < 0.01). The sympathetic activation seen in high-normal BP was coupled with an impairment of baroreflex HR control (but not MSNA) and with a significant increase in HOMA Index, which showed a significant direct relationship with MSNA. CONCLUSION: Thus, independently of which BP the diagnosis is based, high-normal BP is a condition characterized by a sympathetic activation. This neurogenic alteration, which is likely to be triggered by metabolic rather than reflex alterations, might be involved, together with other factors, in the progression of the condition to established hypertension.

Relationship among morning blood pressure surge, 24-hour blood pressure variability, and cardiovascular outcomes in a white population.

Cardiovascular events have their greatest prevalence in the early morning period. Whether this is attributable to an arousal-dependent blood pressure (BP) increase is far from being clear. It is also not clear to what extent this phenomenon reflects overall 24-hour BP variability. In 2051 subjects (aged 25-74 years) representative of the population of Monza (Italy), we measured 24-hour ambulatory systolic BP (SBP) and calculated the difference between the 2-hour average values after morning arousal and the lowest 3 or average 2-hour values before arousal (morning BP surge 1 and 2, respectively). For either measure, we sought the relationship with a variety of indices of 24-hour SBP variability and collected information on (1) the occurrence of cardiovascular and all cause deaths during a follow-up of ≈16 years and (2) the appearance of echocardiographic left ventricular hypertrophy after 10 years from the baseline visit. Morning SBP surge 1 was directly related to indices of 24-hour SBP variability, including those made independent on the magnitude of the day-night SBP difference. There was a weak positive relationship between morning SBP surge 1 and the risk of cardiovascular and all-cause death, which disappeared after adjustment for confounders. This was the case also for development of left ventricular hypertrophy. Morning SBP surge 2 was smaller, inconsistently related to 24-hour SBP variability and not at all related to fatal events or new-onset left ventricular hypertrophy. In a white population, morning BP surge was not found to be an independent predictor of cardiovascular death, all-cause death, or development of high cardiovascular risk (as documented by new-onset cardiac damage) even when appropriately assessed by measures that reflect its association with 24-hour BP variability.

Blood pressure control in Italian essential hypertensives treated by general practitioners.

BACKGROUND: Adequate control of blood pressure (BP) is limited worldwide. This has serious consequences for public health because in hypertensive patients, uncontrolled BP is associated with a higher incidence of cardiovascular events, particularly stroke. The aim of this study was to investigate BP control in a cohort of treated patients with diagnosed hypertension, who were under general practitioner care in Italy. METHODS: Data were collected by 2,643 physicians on 8,572 individual Italian patients. Office BP was measured 5 min after seating each patient and then 3-5 min later. For each patient, data such as medical history of patients, physical examination data, antihypertensive drug usage, and self-BP measurement frequency were obtained. RESULTS: Male prevalence was 48.4%, and mean age was 64.3 ± 10.5 years. Based on the second measurement, BP control (<140/90 mm Hg) was observed in 33.5% of all patients (34.2% in men and 33.4% in women). BP control was much lower for systolic BP than for diastolic BP (35.9 vs. 61.3%, P < 0.0001); moreover, BP control was much more common in patients who were engaged in self-BP measurement (61.2 vs. 38.8%, P < 0.0001). A stricter BP control recommended by the guidelines of the European Society of Hypertension (ESH) and European Society of Cardiology (ESC) (<130/80 mm Hg) was observed in only 5.5% of diabetic patients. CONCLUSIONS: In treated Italian hypertensives effective BP control remains uncommon largely due to the failure to appropriately reduce the systolic BP. The stricter values recommended by the ESH/ESC guidelines for diabetic patients are achieved only by a small fraction of hypertensive diabetic population.

Comparison of echotracking and magnetic resonance assessment of abdominal aorta distensibility and relationships with pulse wave velocity.

Arterial distensibility can be measured either by echotracking or by nuclear magnetic resonance (MRI). Little information, however, is available on the comparison between the two methods and on the relationships between the results obtained with the two approaches and the arterial stiffness gold standard measurement, i.e., pulse wave velocity (PWV). In 28 normotensive subjects (age 33.0 ± 10.4 years, mean ± SD) we measured aortic diameter 1 cm above iliac bifurcation, aortic pulse pressure by tonometry and calculated arterial distensibility via the Reneman formulae for both methods. Aortic diameter and aortic distensibility were not superimposable and higher values were systematically detected with the MRI approach than with the ultrasound one. However, PWV showed a significant correlation with aortic distensibility values obtained by both methods (r = 0.50 and r = 0.49, p < 0.05). These data provide evidence that MRI-measured distensibility value is higher than that obtained via echotracking. The significant correlation with PWV, however, suggests that both methods can be regarded as valuable approaches. Considering the greater economic cost and the lower availability in daily clinical and research practice of MRI, echotracking ultrasonography can be regarded as a reliable and feasible method to assess aortic distensibility.