Upper extremity deep vein thrombosis in COVID-19: Incidence and correlated risk factors in a cohort of non-ICU patients.

BACKGROUND: Venous thromboembolism is a frequent complication of COVID-19 infection. Less than 50% of pulmonary embolism (PE) is associated with the evidence of deep venous thrombosis (DVT) of the lower extremities. DVT may also occur in the venous system of the upper limbs especially if provoking conditions are present such as continuous positive airway pressure (CPAP). The aim of this study was to evaluate the incidence of UEDVT in patients affected by moderate-severe COVID-19 infection and to identify potential associated risk factors for its occurrence. METHODS: We performed a retrospective analysis of all patients affected by moderate-severe COVID-19 infection admitted to our unit. In accordance with the local protocol, all patients had undergone a systematic screening for the diagnosis of UEDVT, by vein compression ultrasonography (CUS). All the patients were receiving pharmacological thromboprophylaxis according to international guidelines recommendations. Univariate and multivariate analyses were used to identify risk factors associated with UEDVT. RESULTS: 257 patients were included in the study, 28 patients were affected by UEDVT with an incidence of 10.9% (95% CI, 7.1-14.7). At univariate analysis UEDVT appeared to be significantly associated (p< 0.05) with pneumonia, ARDS, PaO2/FiO2, D-dimer value higher than the age adjusted cut off value and need for CPAP ventilation. Multivariate analysis showed a significant association between UEDVT and the need for CPAP ventilation (OR 5.95; 95% IC 1.33-26.58). Increased mortality was found in patients affected by UEDVT compared to those who were not (OR 3.71; 95% CI, 1.41-9.78). CONCLUSIONS: UEDVT can occur in COVID-19 patients despite adequate prophylaxis especially in patients undergoing helmet CPAP ventilation. Further studies are needed to identify the correct strategy to prevent DVT in these patients.

Suspected myocarditis in patients with COVID-19: A multicenter case series.

ABSTRACT: Although myocarditis can be a severe cardiac complication of COVID-19 patients, few data are available in the literature about the incidence and clinical significance in patients affected by SARS-CoV-2. This study aims to describe the prevalence and the clinical features of suspected myocarditis in 3 cohorts of patients hospitalized for COVID-19. We retrospectively evaluated all the consecutive patients admitted for COVID-19 without exclusion criteria. Suspect myocarditis was defined according to current guidelines. Age, sex, in-hospital death, length of stay, comorbidities, serum cardiac markers, interleukin-6, electrocardiogram, echocardiogram, and therapy were recorded. Between March 4 to May 20, 2020, 1169 patients with COVID-19 were admitted in 3 Italian Medicine wards. 12 patients (1%) had suspected acute myocarditis; 5 (41.7%) were men, mean age was 76 (SD 11.34; median 78.5 years); length of stay was 38 days on average (SD 8, median value 37.5); 3 (25%) patients died. 8 (66.7%) had a history of cardiac disease; 7 (58.33%) patients had other comorbidities like diabetes, chronic obstructive pulmonary disease, or renal insufficiency. Myocarditis patients had no difference in sex prevalence, rate of death, comorbidities, elevations in serum cardiac markers as compared with patients without myocardial involvement. Otherwise, there was a significantly higher need for oxygen-support and a higher prevalence of cardiac disease in the myocarditis group. Patients with suspected myocarditis were older, had a higher frequency of previous cardiac disease, and significantly more prolonged hospitalization and a lower value of interleukin-6 than other COVID-19 patients. Further studies, specifically designed on this issue, are warranted.

Bedside Abdominal Ultrasound in Evaluating Nasogastric Tube Placement: A Multicenter, Prospective, Cohort Study.

BACKGROUND: Chest radiography is universally accepted as the method of choice to confirm correct positioning of a nasogastric tube (NGT). Considering also that radiation exposure could increase with multiple insertions in a single patient, bedside abdominal ultrasound (BAU) may be a potentially useful alternative to chest radiography in the management of NGTs. RESEARCH QUESTION: What is the accuracy of BAU in confirming the correct positioning of an NGT? STUDY DESIGN AND METHODS: After a specific course consisting of 10 h of training, the authors studied, in a prospective multicenter cohort, the validity of BAU to confirm correct NGT placement. All patients were also evaluated by auscultation (whoosh test) and by chest radiography. Every involved operator was blind to each other. Interobserver agreement and accuracy analyses were calculated. RESULTS: This study evaluated 606 consecutive inpatients with an indication for NGT insertion. Eighty patients were excluded for protocol violation or incomplete examinations and 526 were analyzed. BAU was positive, negative, and inconclusive in 415 (78.9%), 71 (13.5%), and 40 (7.6%), respectively. The agreement between BAU and chest radiography was excellent. Excluding inconclusive results, BAU had a sensitivity of 99.8% (99.3%-100%), a specificity of 91.0% (88.5%-93.6%), a positive predictive value of 98.3% (97.2%-99.5%), and a negative predictive value of 98.6% (97.6%-99.7%). The accuracy of BAU slightly changed according to the different assignments of the uncertain cases and was improved by the exclusion of patients with an altered level of consciousness. INTERPRETATION: These results suggest that BAU has a good positive predictive value and may confirm the correct placement of NGTs when compared with chest radiography. However, considering its suboptimal specificity, caution is necessary before implementing this technique in clinical practice.

Timing of initiation of oral anticoagulants in patients with acute ischemic stroke and atrial fibrillation comparing posterior and anterior circulation strokes.

INTRODUCTION: The aim of this study in patients with acute posterior ischaemic stroke (PS) and atrial fibrillation (AF) was to evaluate (1) the risks of recurrent ischaemic event and severe bleeding and (2) these risks in relation with oral anticoagulant therapy (OAT) and its timing. MATERIALS AND METHODS: Patients with PS were prospectively included; the outcome events of these patients were compared with those of patients with anterior stroke (AS) which were taken from previous registries. The primary outcome was the composite of stroke recurrence, transient ischaemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding and major extracranial bleeding occurring within 90 days from acute stroke. RESULTS: A total of 2470 patients were available for the analysis: 473 (19.1%) with PS and 1997 (80.9%) with AS. Over 90 days, 213 (8.6%) primary outcome events were recorded: 175 (8.7%) in patients with AS and 38 (8.0%) in those with PS. In patients who initiated OAT within 2 days, the primary outcome occurred in 5 out of 95 patients (5.3%) with PS compared to 21 out of 373 patients (4.3%) with AS (OR 1.07; 95% CI 0.39-2.94). In patients who initiated OAT between days 3 and 7, the primary outcome occurred in 3 out of 103 patients (2.9%) with PS compared to 26 out of 490 patients (5.3%) with AS (OR 0.54; 95% CI 0.16-1.80). DISCUSSION: our findings suggest that, when deciding the time to initiate oral anticoagulation, the location of stroke, either anterior or posterior, does not predict the risk of outcome events. CONCLUSIONS: Patients with PS or AS and AF appear to have similar risks of ischaemic or haemorrhagic events at 90 days with no difference concerning the timing of initiation of OAT.

New method to measure and improve consistency of baroreflex sensitivity values.

OBJECTIVE: Baroreflex sensitivity (BRS) is an important prognostic index in cardiovascular diseases, however, its use is complicated by different methods difficult to compare and standardize, often providing conflicting results. We tested whether the simple ratio of RR interval to systolic blood pressure global variabilities (assessed by standard deviations) is a reliable measure of BRS, by measuring the agreement with six established methods. In addition, we tested whether high-pass filtering of data, by removing slow non-baroreflex-mediated fluctuations, could improve the agreement between different BRS methods. METHODS: In 1,409 subjects, we compared 6 established methods (derived by cross-spectral and sequence analysis) and the new method, supine and in response to tilting (1,175 subjects). Data were analyzed after linear detrending, high-pass filtering at 0.025 and 0.05 Hz. RESULTS: Although all seven methods showed a general agreement, the new method consistently showed the lowest distance from the median of the remaining methods (0.04 ± 0.06 ms/mmHg over 2,584 files, p < 0.05 with respect to the second best method). High-pass filtering improved (p < 0.001) the agreement between methods without reducing the sensitivity to changes induced by tilting. Only the new method could provide estimates in all 2,584 files tested. INTERPRETATION: The new method intercepts the mean information of all other methods better than any other method, hence providing a simple, easy to standardize (no mathematical constraints) and yet robust and reliable BRS estimate. High-pass filtering markedly improves the agreement of all methods, without loss of sensitivity, and could be routinely used in clinical trials, to provide comparable BRS estimates.

Dynamic interactions between musical, cardiovascular, and cerebral rhythms in humans.

BACKGROUND: Reactions to music are considered subjective, but previous studies suggested that cardiorespiratory variables increase with faster tempo independent of individual preference. We tested whether compositions characterized by variable emphasis could produce parallel instantaneous cardiovascular/respiratory responses and whether these changes mirrored music profiles. METHODS AND RESULTS: Twenty-four young healthy subjects, 12 musicians (choristers) and 12 nonmusician control subjects, listened (in random order) to music with vocal (Puccini's "Turandot") or orchestral (Beethoven's 9th Symphony adagio) progressive crescendos, more uniform emphasis (Bach cantata), 10-second period (ie, similar to Mayer waves) rhythmic phrases (Giuseppe Verdi's arias "Va pensiero" and "Libiam nei lieti calici"), or silence while heart rate, respiration, blood pressures, middle cerebral artery flow velocity, and skin vasomotion were recorded.Common responses were recognized by averaging instantaneous cardiorespiratory responses regressed against changes in music profiles and by coherence analysis during rhythmic phrases. Vocal and orchestral crescendos produced significant (P=0.05 or better) correlations between cardiovascular or respiratory signals and music profile, particularly skin vasoconstriction and blood pressures, proportional to crescendo, in contrast to uniform emphasis, which induced skin vasodilation and reduction in blood pressures. Correlations were significant both in individual and group-averaged signals. Phrases at 10-second periods by Verdi entrained the cardiovascular autonomic variables. No qualitative differences in recorded measurements were seen between musicians and nonmusicians. CONCLUSIONS: Music emphasis and rhythmic phrases are tracked consistently by physiological variables. Autonomic responses are synchronized with music, which might therefore convey emotions through autonomic arousal during crescendos or rhythmic phrases.

Interaction between central-peripheral chemoreflexes and cerebro-cardiovascular control.

We investigated the interaction between hypoxia and hypercapnia on ventilation and on cerebro-cardio-vascular control. A group of 12 healthy subjects performed rebreathing tests to determine the ventilatory response to hypoxia, at different levels of carbon dioxide (CO(2)), and to normoxic hypercapnia. Oxygen saturation (SaO(2)), end-tidal CO(2) (et-CO(2)), minute ventilation, blood pressure, R-R interval and mid-cerebral artery flow velocity (MCFV) were continuously recorded. The hypoxic ventilatory response significantly increased under hypercapnia and decreased under hypocapnia (slopes L/min/% Sa O(2): -0.33 +/- 0.05, -0.74 +/- 0.02 and -1.59 +/- 0.3, p < 0.0001, in hypocapnia, normocapnia and hypercapnia, respectively). At similar degrees of ventilation, MCFV increased more markedly during normocapnic hypoxia than normoxic hypercapnia; the slopes linking MCFV to hypoxia remained unchanged at increasing levels of et-CO(2), whereas the regression lines were shifted upward. The R-R interval decreased more markedly during normocapnic hypoxia than normoxic hypercapnia and the arterial baroreflex sensitivity was decreased only by hypoxia. Cardiovascular responses to hypoxia were not affected by different levels of et-CO(2). We conclude that concomitant hypoxia and hypercapnia, while increasing ventilation synergistically, exert an additive effect on cerebral blood flow. Increased sympathetic activity (and reduced baroreflex sensitivity) is one of the mechanisms by which hypoxia stimulates cardiac sympathetic activity.

Slow breathing improves arterial baroreflex sensitivity and decreases blood pressure in essential hypertension.

Sympathetic hyperactivity and parasympathetic withdrawal may cause and sustain hypertension. This autonomic imbalance is in turn related to a reduced or reset arterial baroreflex sensitivity and chemoreflex-induced hyperventilation. Slow breathing at 6 breaths/min increases baroreflex sensitivity and reduces sympathetic activity and chemoreflex activation, suggesting a potentially beneficial effect in hypertension. We tested whether slow breathing was capable of modifying blood pressure in hypertensive and control subjects and improving baroreflex sensitivity. Continuous noninvasive blood pressure, RR interval, respiration, and end-tidal CO2 (CO2-et) were monitored in 20 subjects with essential hypertension (56.4+/-1.9 years) and in 26 controls (52.3+/-1.4 years) in sitting position during spontaneous breathing and controlled breathing at slower (6/min) and faster (15/min) breathing rate. Baroreflex sensitivity was measured by autoregressive spectral analysis and "alpha angle" method. Slow breathing decreased systolic and diastolic pressures in hypertensive subjects (from 149.7+/-3.7 to 141.1+/-4 mm Hg, P<0.05; and from 82.7+/-3 to 77.8+/-3.7 mm Hg, P<0.01, respectively). Controlled breathing (15/min) decreased systolic (to 142.8+/-3.9 mm Hg; P<0.05) but not diastolic blood pressure and decreased RR interval (P<0.05) without altering the baroreflex. Similar findings were seen in controls for RR interval. Slow breathing increased baroreflex sensitivity in hypertensives (from 5.8+/-0.7 to 10.3+/-2.0 ms/mm Hg; P<0.01) and controls (from 10.9+/-1.0 to 16.0+/-1.5 ms/mm Hg; P<0.001) without inducing hyperventilation. During spontaneous breathing, hypertensive subjects showed lower CO2 and faster breathing rate, suggesting hyperventilation and reduced baroreflex sensitivity (P<0.001 versus controls). Slow breathing reduces blood pressure and enhances baroreflex sensitivity in hypertensive patients. These effects appear potentially beneficial in the management of hypertension.

Effects of unilateral and bilateral carotid baroreflex stimulation on cardiac and neural sympathetic discharge oscillatory patterns.

BACKGROUND: Left and right carotid baroreflex afferents participate in generating the spontaneous variability of heart rate (HR), arterial pressure (AP), and muscle sympathetic nerve activity (MSNA), but the relative contribution of each side is unclear. Pathophysiological conditions unilaterally affecting carotid baroreceptor function might result in abnormal changes of HR, AP, and MSNA variability, thus markedly affecting prognosis. We tested the hypothesis that unilateral carotid baroreceptor perturbation might differentially affect HR, AP, and MSNA variability compared with stimulation of the opposite side. METHODS AND RESULTS: In 12 healthy volunteers, 4 sinusoidal neck suction procedures (0.1 Hz, from 0 to -50 mm Hg) were applied at the right, left, and combined right and left sides of the neck, in concordance or with phase opposition. Respiration was controlled at 0.25 Hz. Power spectrum analysis assessed the changes in the 0.1-Hz oscillatory component of the R-R interval, systolic AP (SAP), and MSNA variability induced by rhythmic baroreceptor stimulation. Mean R-R interval, SAP, and MSNA were unchanged during all procedures. The increase of the 0.1-Hz component of R-R and SAP variability during right and combined right and left carotid baroreceptor stimulation was greater than the changes induced by left-sided stimulation. The increase in the 0.1-Hz oscillatory component of MSNA variability was similar during all neck suction procedures. CONCLUSIONS: Right carotid baroreflex loading was as efficient as bilateral stimulation and more effective than left carotid suction in modulating R-R and SAP variability. There was no asymmetry in neural sympathetic discharge responses after single-sided carotid baroreceptor stimulation.

Slow breathing increases arterial baroreflex sensitivity in patients with chronic heart failure.

BACKGROUND: It is well established that a depressed baroreflex sensitivity may adversely influence the prognosis in patients with chronic heart failure (CHF) and in those with previous myocardial infarction. METHODS AND RESULTS: We tested whether a slow breathing rate (6 breaths/min) could modify the baroreflex sensitivity in 81 patients with stable (2 weeks) CHF (age, 58+/-1 years; NYHA classes I [6 patients], II [33], III [27], and IV [15]) and in 21 controls. Slow breathing induced highly significant increases in baroreflex sensitivity, both in controls (from 9.4+/-0.7 to 13.8+/-1.0 ms/mm Hg, P<0.0025) and in CHF patients (from 5.0+/-0.3 to 6.1+/-0.5 ms/mm Hg, P<0.0025), which correlated with the value obtained during spontaneous breathing (r=+0.202, P=0.047). In addition, systolic and diastolic blood pressure decreased in CHF patients (systolic, from 117+/-3 to 110+/-4 mm Hg, P=0.009; diastolic, from 62+/-1 to 59+/-1 mm Hg, P=0.02). CONCLUSIONS: These data suggest that in patients with CHF, slow breathing, in addition to improving oxygen saturation and exercise tolerance as has been previously shown, may be beneficial by increasing baroreflex sensitivity.