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Background Nursing home (NH) residents have been dramatically affected by COVID-19, with extremely high rates of hospitalization and mortality. Aims To describe the features and impact of an assistance model involving an intermediate care mobile medical specialist team (GIROT, Gruppo Intervento Rapido Ospedale Territorio) aimed at delivering “hospital-at-nursing home” care to NH residents with COVID-19 in Florence, Italy. Methods The GIROT activity was set-up during the first wave of the pandemic (W1, March–April 2020) and became a structured healthcare model during the second (W2, October 2020–January 2021). The activity involved (1) infection transmission control among NHs residents and staff, (2) comprehensive geriatric assessment including prognostication and geriatric syndromes management, (3) on-site diagnostic assessment and protocol-based treatment of COVID-19, (4) supply of nursing personnel to understaffed NHs. To estimate the impact of the GIROT intervention, we reported hospitalization and infection lethality rates recorded in SARS-CoV-2-positive NH residents during W1 and W2. Results The GIROT activity involved 21 NHs (1159 residents) and 43 NHs (2448 residents) during W1 and W2, respectively. The percentage of infected residents was higher in W2 than in W1 (64.5% vs. 38.8%), while both hospitalization and lethality rates significantly decreased in W2 compared to W1 (10.1% vs 58.2% and 23.4% vs 31.1%, respectively). Discussion Potentiating on-site care in the NHs paralleled a decrease of hospital admissions with no increase of lethality. Conclusions An innovative “hospital-at-nursing home” patient-centred care model based on comprehensive geriatric assessment may provide a valuable contribution in fighting COVID-19 in NH residents.

Background We hypothesized that cardiovascular physiology differs in reflex syncope patients compared with the general population, predisposing such individuals to vasovagal reflex. Methods In this multicohort cross-sectional study, we compared aggregate data of resting SBP, DBP, pulse pressure (PP) and heart rate (HR), collected from six community-based cohort studies (64 968 observations) with those from six databases of reflex syncope patients (6516 observations), subdivided by age decades and sex. Results Overall, in male individuals with reflex syncope, SBP (-3.4 mmHg) and PP (-9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages above 60 years. In female individuals, PP (-6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with male individuals, SBP in female individuals exhibited slower increase until age 40 years, and then demonstrated steeper increase that continued throughout remaining life. Conclusion The patients prone to reflex syncope demonstrate a different resting cardiovascular haemodynamic profile as compared with a general population, characterized by lower SBP and PP, reflecting reduced venous return and lower stroke volume, and a higher HR and DBP, suggesting the activation of compensatory mechanisms. Our data contribute to a better understanding why some individuals with similar demographic characteristics develop reflex syncope and others do not. Video abstract http://links.lww.com/HJH/B580.

Aims Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. The study hypothesis was that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. Methods and results ABPM data from reflex syncope patients and controls, matched by average 24 h SBP, age, sex, and hypertension were compared. Patients with constitutional hypotension, orthostatic hypotension, and predominant cardioinhibition during carotid sinus massage or prolonged electrocardiogram monitoring or competing causes of syncope were excluded. Daytime and nighttime SBP drops ( Conclusion SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

Purpose of Review To review the blood pressure (BP) effects of pain and analgesic medications and to help interpret BP changes in people suffering from acute or chronic pain. Recent Findings Acute pain evokes a stress response which prompts a transient BP increase. Chronic pain is associated with impaired regulation of cardiovascular and analgesia systems, which may predispose to persistent BP elevation. Also analgesics may have BP effects, which vary according to the drug class considered. Data on paracetamol are controversial, while multiple studies indicate that non-steroidal anti-inflammatory drugs may increase BP, with celecoxib showing a lesser impact. Hypotension has been reported with opioid drugs. Among adjuvants, tricyclic antidepressants and serotonin-norepinephrine reuptake inhibitors could be pro-hypertensive due to potentiation of adrenergic transmission. Summary Pain and analgesics may induce a clinically significant BP destabilization. The implications on hypertension incidence and BP control remain unclear and should be explored in future studies. Graphical abstract

Objective: Diagnostic criteria for ambulatory blood pressure monitoring (ABPM) in patients with suspected reflex syncope are lacking. We hypothesized that patients with reflex syncope have a higher prevalence of systolic blood pressure (SBP) drops on ABPM. Design and method: We conducted a retrospective analysis comparing ABPM data from reflex syncope patients and controls, matched by average 24-hour SBP, age, sex and hypertension. Patients with constitutional hypotension, orthostatic hypotension, predominant cardioinhibition or competing causes of syncope were excluded. Daytime and night-time SBP drops ( 90% and 80–90%, respectively. Findings were validated in an independent sample. Results: In the Derivation cohort, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drop < 90 mmHg provided the best diagnostic yield (91% specificity, 32% sensitivity, Odds Ratio [OR] = 4.6, p = 0.001). Two or more-daytime drops < 100 mmHg achieved 84% specificity and 40% sensitivity (OR = 3.5, p = 0.001). Results were confirmed in the Validation cohort: one or more daytime SBP drop < 90 mmHg provided 94% specificity and 29% sensitivity (OR = 6.2, p < 0.001), while two or more daytime SBP drops < 100 mmHg achieved 83% specificity and 35% sensitivity (OR = 3.5, p < 0.001) Conclusions: SBP drops during ABPM are more common in reflex syncope patients than in controls. Cut-off values that may be applied in clinical practice are defined. This study expands the current indications for ABPM to patients with reflex syncope.

Aims Indications, methodology, and diagnostic criteria for carotid sinus massage (CSM) and tilt testing (TT) have been standardized by the 2018 Guidelines on Syncope of the European Society of Cardiology. Aim of this study was to assess their effectiveness in a large cohort which reflects the performance under ‘real-world’ conditions. Methods and results We analysed all patients who had undergone CSM and TT in the years 2003–2019 for suspected reflex syncope. Carotid sinus massage was performed according to the ‘Method of Symptoms’. Tilt testing was performed according to the ‘Italian protocol’ which consists of a passive phase followed by a sublingual nitroglycerine phase. For both tests, positive test was defined as reproduction of spontaneous symptoms in the presence of bradycardia and/or hypotension. Among 3293 patients (mean age 73 ± 12 years, 48% males), 2019 (61%) had at least one test positive. A bradycardic phenotype was found in 420 patients (13%); of these, 60% were identified by CSM, 37% by TT, and 3% had both test positive. A hypotensive phenotype was found in 1733 patients (53%); of these, 98% were identified by TT and 2% had both TT and CSM positive. Conclusion The overall diagnostic yield of the tests in patients >40-year-old with suspected reflex syncope was 61%. Both CSM and TT are useful for identifying those patients with a bradycardic phenotype, whereas CSM has a limited value for identifying the hypotensive phenotype. Since the overlap of responses between tests is minimal, both CSM and TT should be performed in every patient over 40 years receiving investigation for unexplained but possible reflex syncope.

Orthostatic hypotension (OH) is an abnormal blood pressure response to standing, which is associated with an increased risk of adverse outcomes such as syncope, falls, cognitive impairment, and mortality. Medical therapy is one the most common causes of OH, since numerous cardiovascular and psychoactive medications may interfere with the blood pressure response to standing, leading to drug-related OH. Additionally, hypotensive medications frequently overlap with other OH risk factors (e.g., advanced age, neurogenic autonomic dysfunction, and comorbidities), thus increasing the risk of symptoms and complications. Consequently, a medication review is recommended as a first-line approach in the diagnostic and therapeutic work-up of OH, with a view to minimizing the risk of drug-related orthostatic blood pressure impairment. If symptoms persist after the review of hypotensive medications, despite adherence to non-pharmacological interventions, specific drug treatment for OH can be considered. In this narrative review we present an overview of drugs acting on the cardiovascular and central nervous system that may potentially impair the orthostatic blood pressure response and we provide practical suggestions that may be helpful to guide medical therapy optimization in patients with OH. In addition, we summarize the available strategies for drug treatment of OH in patients with persistent symptoms despite non-pharmacological interventions.

AIMS: Unexplained syncope is an important clinical challenge. The influence of age at first syncope on the final syncope diagnosis is not well studied. METHODS AND RESULTS: Consecutive head-up tilt patients (n = 1928) evaluated for unexplained syncope were stratified into age groups 1 concurrent diagnosis; 14 vs. 26%, P

This review addresses tilt-testing methodology by searching the literature which reports timing of asystole and loss of consciousness (LOC). Despite the Italian protocol being the most widely adopted, its stipulations are not always followed to the letter of the European Society of Cardiology guidelines. The discrepancies permit reassessment of the incidence of asystole when tilt-down is early, impending syncope, compared with late, established LOC. Asystole is uncommon with early tilt down and diminishes with increasing age. However, if LOC is established as test-end, asystole is more common, and it is age-independent. Thus, the implications are that asystole is commonly under-diagnosed by early tilt-down. The prevalence of asystolic responses observed using the Italian protocol with a rigorous tilt down time is numerically close to that observed during spontaneous attacks by electrocardiogram loop recorder. Recently, tilt-testing has been questioned as to its validity but, in selection of pacemaker therapy in older highly symptomatic vasovagal syncope patients, the occurrence of asystole has been shown to be an effective guide for treatment. The use of head-up tilt test as an indication for cardiac pacing therapy requires pursuing the test until complete LOC. This review offers explanations for the findings and their applicability to practice. A novel interpretation is offered to explain why pacing induced earlier may combat vasodepression by raising the heart rate when sufficient blood remains in the heart.

Purpose: Home blood pressure monitoring (HBPM) might be considered a valid alternative to ambulatory blood pressure monitoring (ABPM) for both the diagnosis and management of hypertension. Correct information on how to perform HBPM are crucial for its reliability. The aim of the present survey was to assess if hypertensive patients followed current recommendation on how to correctly perform HBPM measurements. Materials and methods: The survey included 30 different items on how to perform the HBPM. It was developed by the ‘Young Investigators’ group of the Italian Society of Arterial Hypertension (SIIA) and it was administered during the office visit between May 2019 and December 2021. Results: A total of 643 hypertensive patients participated in the study. Main results show that, despite the rate of informed patients was relatively high (71% of the whole population), unacceptable number of patients did not follow indications on how to perform a correct HBPM. Patients who were informed on how to measure home BP had a significantly higher rate of correct position during measurement (78 vs. 22%, p < 0.01), avoidance of talking and moving during measurement (68 vs. 32%, p < 0.0001), and correct number and time interval between two measurements (85 vs. 15%, p < 0.001). More accurate measurements of home BP were associated with less prevalence of carotid plaque. Conclusions: Correct performance for HBPM is low among patients treated in Italian hypertension centers. These findings shed light on the importance of correct HBPM measurements for the detection of accurate BP values for the proper management of hypertensive patients.

SARS-CoV-2 vaccination has significantly reduced infection, hospitalization, and lethality rates among nursing home (NH) residents, but durability of vaccine effects remains unknown. This study investigated the long-term impact of BNT162b2 SARS-CoV-2 vaccine on breakthrough infection rates in the NHs of Florence, Italy.Participants included residents living in Florence NHs as of April 1st, 2021, who had completed the primary SARS-CoV2 vaccination course by February 15th, 2021. Weekly rates of breakthrough infection were calculated between April 1st and October 31st 2021, with 7-day incidence defined as the number of new confirmed SARS-CoV-2-positive residents over the vaccinated resident census. Hospital admissions and deaths were recorded from local administrative and clinical sources. Patients admitted to NHs after April 1st were excluded to avoid confounding effect of different vaccination timing.Among 2271 vaccinated residents (mean age 86.6, 74% female), we recorded 105 cases of breakthrough infections. Rates of breakthrough infection remained very low in the 6 months after vaccination, but started to rise over the following months, peaking at 0.94%, and then became stable around 0.2%-0.3%. Over the study period, infection rates remained low as compared to the incidence of SARS-CoV-2 infection during pre-vaccination period. Overall hospitalization and lethality rates were 8%.Among vaccinated NH residents, rates of breakthrough SARS-CoV-2 infection, hospitalization and lethality remained low up to 9 months following primary vaccination course. A mild resurgence of SARS-CoV-2 infection, after 6 months from vaccination, suggests a decline of vaccine effectiveness in preventing transmission.

Syncope is a frequent event in the general population. Approximately 1%-2% of all emergency department admissions are due to syncope and at least one third of all people experience fainting in their life. Although consequences of cardiac syncope are generally feared, non-cardiac syncope is much more common and may be associated with severe injuries and quality of life impairment, particularly in older adults. Various diagnostic and therapeutic strategies have been created and implemented over decades, leading to significant improvements in diagnostic accuracy and treatment effectiveness. In recent years, diagnosis and treatment have further evolved according to an innovative approach focused on the hemodynamic mechanism underlying syncope, based upon the assumption that knowledge of syncope mechanism is a prerequisite for effective syncope prevention and treatment. Therefore, a new classification of syncope has been proposed, which defines two main syncope phenotypes with different predominant mechanisms: the hypotensive phenotype, where hypotension or vasodepression prevails, and the bradycardic phenotype, where cardioinhibition prevails. Identification of syncope phenotype - bradycardic or hypotensive/vasodepressive - represents the first step towards a personalized management of syncope, characterized by customized interventions for prevention. The present review is aimed at illustrating these new developments in diagnosis and therapy of non-cardiac syncope within a mechanism-based perspective. Diagnosis and therapy of bradycardic and hypotensive phenotypes are discussed, with a focus on recent evidence.

Background Syncope is a common clinical problem with a sharp rise in the incidence after 70 years. In older patients, syncope is often a diagnostic challenge. It is unclear whether the age at which patients experience syncope for the first time impacts the results of syncope investigation. Purpose To study the influence of early-onset vs. mature-onset syncope on clinical characteristics and final head-up tilt (HUT) diagnosis in a large sample of unexplained syncope patients. Methods Consecutive patients (n=1928) with unexplained syncope after initial evaluation examined with a standard HUT protocol in a syncope unit were stratified into age groups below and above 60 years. Clinical characteristics and the final HUT diagnosis were analysed in relation to self-reported age at first syncope and age at investigation. The distribution of age at first syncope was bimodal with peaks at 15 and 70 years (Figure 1). In the present analysis, patients aged >60 years (n=836) with early-onset (60 years) syncope were compared. Results Vasovagal syncope (VVS) was more common in early-onset syncope, 39% vs 19% (p60 years.Complex syncope etiology (findings suggesting overlap between VVS, OH and/or CSS) was more common among patients with early-onset syncope, 37% vs 26% (p=0.023). No definite HUT-derived diagnosis was more common in mature-onset syncope, 23% vs 13% (p=0.023). Heart failure, 9% vs 2% (p=0.024) and atrial fibrillation, 20% vs 9% (p=0.013) were more common in mature-onset syncope. Prodromes were less common in mature-onset syncope, 26% vs 52% (p Conclusions Mature-onset syncope was more often associated with absence of prodromes, orthostatic hypotension, inconclusive HUT findings and presence of heart failure and atrial fibrillation suggesting cardiac syncope to be the likely cause. Early-onset syncope was associated with presence of prodromes, vasovagal reflex mechanism and complex syncope diagnosis. Lifelong and mature-onset unexplained syncope may have different pathophysiological mechanisms in older patients and aetiologies other than vasovagal syncope should be carefully considered in patients with first-ever syncope in later life. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swedish heart and lung foundationCrafoord foundation

Evidence on the effectiveness of SARS-CoV-2 vaccines in nursing home (NHs) residents is limited. We examined the impact of the BNT162b2 mRNA SARS-CoV-2 vaccine on the course of the epidemic in NHs in the Florence Health District, Italy, before and after vaccination. Moreover, we assessed survival and hospitalization by vaccination status in SARS-CoV-2-positive cases occurring during the post-vaccination period. We calculated the weekly infection rates during the pre-vaccination (1 October–26 December 2020) and post-vaccination period (27 December 2020–31 March 2021). Cox analysis was used to analyze survival by vaccination status. The study involved 3730 residents (mean age 84, 69% female). Weekly infection rates fluctuated during the pre-vaccination period (1.8%–6.5%) and dropped to zero during the post-vaccination period. Nine unvaccinated (UN), 56 partially vaccinated (PV) and 35 fully vaccinated (FV) residents tested SARS-CoV-2+ during the post-vaccination period. FV showed significantly lower hospitalization and mortality rates than PV and UV (hospitalization: FV 3%, PV 14%, UV 33%; mortality: FV 6%, PV 18%, UV 56%). The death risk was 84% and 96% lower in PV (HR 0.157, 95%CI 0.049–0.491) and FV (HR 0.037, 95%CI 0.006–0.223) versus UV. SARS-CoV-2 vaccination was followed by a marked decline in infection rates and was associated with lower morbidity and mortality among infected NH residents.

Aims Syncope without prodromes in subjects with normal heart and normal electrocardiogram (ECG) is classified as non-classical neurally mediated syncope and is characterized by low adenosine plasma levels (APLs) and frequent asystolic syncope. We assessed the efficacy of theophylline, a non-selective adenosine receptor antagonist, in preventing syncopal events. Methods and results Participants received an implantable cardiac monitor, underwent APL measurement, and received oral theophylline at maximum tolerated dose (starting dose 300 mg b.i.d.). They were compared with a historical cohort of untreated patients with implantable cardiac monitor who had the same inclusion criteria and were balanced with the propensity score (PS) method as regard age, sex, lifetime syncopal episodes, APL, and antihypertensive drugs. Primary endpoint was time to first syncopal recurrence at 24 months. There were 76 patients in the theophylline group and 58 in the control group. Syncope recurred in 25 (33%) patients in the theophylline group and in 27 (47%) patients in the control group, with an estimated 2-year recurrence rate of 33% and 60%, respectively, and a hazard ratio of 0.53 [95% confidence interval (CI), 0.30–0.95; P = 0.034]. Most of the benefit of theophylline is derived from reduction of syncope due to asystolic atrioventricular (AV) block (hazard ratio of 0.13; 95% CI, 0.03–0.58; P = 0.008). Thirty (39%) patients discontinued theophylline after a median of 6.4 (interquartile range 1.7–13.8) months due to side effects. Conclusion Theophylline was effective in preventing recurrences in patients with syncope without prodromes, normal heart, and normal ECG. The benefit was greater in patients with syncope due to asystolic AV block. ClinicalTrials.gov Identifier NCT03803215.

Background Psychogenic pseudosyncope (PPS), a conversion disorder and syncope mimic, accounts for a large proportion of ‘unexplained syncope’. PPS is diagnosed by reproduction of patients’ symptoms during head-up tilt (HUT). Electroencephalogram (EEG), a time consuming and resource intensive technology, is used during HUT to demonstrate absence of cerebral hypoperfusion during transient loss of consciousness (TLOC). Near-infrared spectroscopy (NIRS) is a simple, non-invasive technology for continuous monitoring of cerebral perfusion. We present a series of patients for whom PPS diagnosis was supported by NIRS during HUT. Methods Eight consecutive patients with suspected PPS referred to a syncope unit underwent evaluation. During HUT, continuous beat-to-beat blood pressure (BP), heart rate (HR) and NIRS-derived tissue saturation index (TSI) were measured. BP, HR and TSI at baseline, time of first symptom, presyncope and apparent TLOC were measured. Patients were given feedback and followed for symptom recurrence. Results Eight predominantly female patients (6/8, 75%) aged 31 years (16–54) were studied with (5/8, 63%) having comorbid psychiatric diagnoses, and (5/8, 63%) presenting with frequent episodes of prolonged TLOC with eyes closed (6/8, 75%). All patients experienced reproduction of typical events during HUT. Systolic BP (mmHg) increased from baseline (129.7 (interquartile range [IQR] 124.9–133.4)) at TLOC (153.0 (IQR 146.7–159.0)) (P-value = 0.012). HR (bpm) increased from baseline 78 (IQR 68.6–90.0) to 115.7 (IQR 93.5–127.9) (P-value = 0.012). TSI (%) remained stable throughout, 71.4 (IQR 67.5–72.9) at baseline vs. 71.0 (IQR 68.2–73.0) at TLOC (P-value = 0.484). Conclusions NIRS provides a non-invasive surrogate of cerebral perfusion during HUT. We propose HUT incorporating NIRS monitoring in the diagnostic algorithm for patients with suspected PPS.

Background Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to unfavorable drug-related effects on cognition and psychomotor functioning. BDZs may also have hypotensive effects, but evidence concerning the relationship between BDZs and orthostatic blood pressure (BP) behaviour in older people is scarce. We investigated the effects of BDZs on BP response to an orthostatic active stand test. Methods We performed a retrospective analysis of data from an outpatient research clinic in an Irish university hospital, where people aged 60 or older underwent a comprehensive geriatric assessment between August 2007 and May 2009. Non-invasive beat-to-beat orthostatic BP was measured during active stand, with systolic BP assessed at each 10-second interval. Information on regular BDZs use was collected. Factors independently associated with orthostatic systolic BP were investigated using multiple linear regression. Results Of 624 community-dwelling people who underwent a clinic assessment, orthostatic active stand data was collected in 541. Information on regular BDZs use was available in 538 people. Of 538 participants, mean age was 72.7±7.2, 67.7% were female and 33 (6.1%) reported regular use of BDZs. History of falls (p=0.027) and fear of falling (p Conclusion BDZs may confer higher risk of an immediate systolic BP drop after standing in older people, which may contribute to their known falls risk. BDZ should be avoided in older people at risk of falling.

The rate of syncope in the Emergency Department ranges between 0.9 and 1.7%. Syncope is mostly related to a underlying reflex or orthostatic mechanism. A bradycardic or a hypotensive phenotype, may be identified. The latter is the most common and could be constitutional or drug induced. Consequently, obtaining an accurate drug history is an important step of the initial assessment of syncope. As anti-hypertensive medication might be responsible for orthostatic hypotension, managing hypertension in patients with syncope requires finding an ideal balance between hypotensive and cardiovascular risks. The choice of anti-hypertensive molecule as well as the therapeutic regimen and dosage, influences the risk of syncope. Not only could anti-hypertensive drugs have a hypotensive effect but opioids and psychoactive medications may also be involved in the mechanism of syncope. Proper drug management could reduce syncope recurrences and their consequences.

The Working Group on Uric Acid and Cardiovascular Risk of the Italian Society of Hypertension conceived and designed an ad hoc study aimed at searching for prognostic cut-off values of serum uric acid (SUA) in predicting combined (fatal and non-fatal) cerebrovascular (CBV) events in the whole database. The URic acid Right for heArt Health study is a nationwide, multicenter, observational cohort study involving data on subjects aged 18-95 years recruited on a regional community basis from all the territory of Italy under the patronage of the Italian Society of Hypertension with a mean follow-up period of 120.7 ± 61.8 months. A total of 14,588 subjects were included in the analysis. A prognostic cut-off value of SUA able to discriminate combined CBV events (>4.79 mg/dL or >284.91 µmol/L) was identified by means of receiver operating characteristic curve in the whole database. Multivariate Cox regression analysis adjusted for confounders (age, sex, arterial hypertension, diabetes, chronic kidney disease, smoking habit, ethanol intake, body mass index, low-density lipoprotein cholesterol, and use of diuretics) identified an independent association between SUA and combined CBV events in the whole database (HR 1.249, 95% confidence interval, 1.041-1.497, p = 0.016). The results of the present study confirm that SUA is an independent risk marker for CBV events after adjusting for potential confounding variables, including arterial hypertension, and demonstrate that >4.79 mg/dL is a valid prognostic cut-off value.

Objectives: In older individuals, the role of serum uric acid (SUA) as risk factor for mortality is debated. This study investigated the association of SUA with all-cause and cardiovascular (CV) mortality in older adults participating in the large multicentre observational uric acid right for heart health (URRAH) study. Methods: Eight thousand URRAH participants aged 65+ were included in the analysis. The predictive role of SUA was assessed using Cox regression models stratified according to the cut-off age of 75. SUA was tested as continuous and categorical variable (age-specific quartiles). The prognostic threshold of SUA for mortality was analysed using receiver operating characteristic curves. Results: Among participants aged 65-74, multivariate Cox regression analysis adjusted for CV risk factors and comorbidities identified an independent association of SUA with both all-cause mortality (hazard ratio [HR] 1.169, 95% confidence interval [CI] 1.107-1.235) and CV mortality (HR 1.146, 95% CI 1.064-1.235). The cut-off value of 4.8 mg/dl discriminated mortality status. In participants aged 75+, we observed a J-shaped relationship of SUA with all-cause and CV mortality, with risk increasing at extreme SUA levels. Conclusions: These results confirmed the predictive role of SUA for all-cause and CV mortality in older adults, while revealing considerable age-related differences. Mortality risk increased at higher SUA levels in participants aged 65-74, with a prognostic threshold of 4.8 mg/dl. The relationship between SUA and mortality was J-shaped in oldest participants. Large interventional studies are needed to clarify the benefits and possible risks of urate-lowering treatments in older adults.

Aims Whether the association between uric acid (UA) and cardiovascular disease is influenced by some facilitating factors is unclear. The aim of this study was to investigate whether the risk of cardiovascular mortality (CVM) associated with elevated UA was modulated by the level of resting heart rate (HR). Methods and results Multivariable Cox analyses were made in 19 128 participants from the multicentre Uric acid Right for heArt Health study. During a median follow-up of 11.2 years, there were 1381 cases of CVM. In multivariable Cox models both UA and HR, either considered as continuous or categorical variables were independent predictors of CVM both improving risk discrimination (P ≤ 0.003) and reclassification (P Conclusion This data suggest that the contribution of UA to determining CVM is modulated by the level of HR supporting the hypothesis that activation of the sympathetic nervous system facilitates the action of UA as a cardiovascular risk factor.

BACKGROUNDWe hypothesized that cardiovascular physiology differs in reflex syncope patients compared with general population, predisposing such subjects to vasovagal reflex.METHODSIn this multicohort cross-sectional study, we compared resting systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP) and heart rate (HR), collected from 6 community-based cohort studies (64,968 observations) with those from 6 databases of reflex syncope patients (6516 observations), subdivided by age decades and sex.RESULTSOverall, in males with reflex syncope, SBP (−3.4 mmHg) and PP (−9.2 mmHg) were lower and DBP (+2.8 mmHg) and HR (+5.1 bpm) were higher than in the general population; the difference in SBP was higher at ages >60 years. In females, PP (−6.0 mmHg) was lower and DBP (+4.7 mmHg) and HR (+4.5 bpm) were higher than in the general population; differences in SBP were less pronounced, becoming evident only above 60 years. Compared with males, SBP in females exhibited slower increase until age 40, and then demonstrated steeper increase that continued throughout life.CONCLUSIONThe patients prone to reflex syncope demonstrate a different resting cardiovascular hemodynamic profile characterized by reduced venous return and stroke volume, evidenced by lower SBP and PP, and compensatory increase in HR and vascular resistance, the latter expressed by elevated DBP. The data presented here contribute to our understanding why some subjects with similar demographic characteristics develop reflex syncope and others not.

Introduction Why some individuals with similar demographic characteristics develop syncope during tilt testing (TT) and others do not is unknown and low test sensitivity is claimed. We sought an alternative explanation; resting cardiovascular physiology differs in patients with positive and negative TT. Methods We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP), and heart rate (HR) using three large syncope patient databases comparing tilt-positive with tilt-negative results after excluding orthostatic hypotension. Positive tilt-response, confirming reflex syncope, was defined as reproduction of spontaneous symptoms with characteristic bradycardia and/or hypotension. Impact of demographic, hemodynamic parameters and prevalent hypertension on TT positivity were assessed using logistic regression models. Results Records of 5236 patients (45% males; mean age, 60±22 years; 32% on antihypertensive therapy) were analyzed. TT was positive in 3129 (60%) and tilt-positive patients had lower SBP (127.2±17.9 vs 129.7±18.0 mmHg, p

Aims Tilt testing (TT) is recognized to be a valuable contribution to the diagnosis and the pathophysiology of vasovagal syncope (VVS). This study aimed to assess the influence of age on TT responses by examination of a large patient cohort. Methods and results Retrospective data from three experienced European Syncope Units were merged to include 5236 patients investigated for suspected VVS by the Italian TT protocol. Tilt testing-positivity rates and haemodynamics were analysed across age-decade subgroups. Of 5236 investigated patients, 3129 (60%) had a positive TT. Cardioinhibitory responses accounted for 16.5% of positive tests and were more common in younger patients, decreasing from the age of 50–59 years. Vasodepressor (VD) responses accounted for 24.4% of positive tests and prevailed in older patients, starting from the age of 50–59. Mixed responses (59.1% of cases) declined slightly with increasing age. Overall, TT positivity showed a similar age-related trend (P = 0.0001) and was significantly related to baseline systolic blood pressure (P Conclusions Age significantly impacts the haemodynamic pattern of TT responses, starting from the age of 50. Conversely, TT phase—passive or TNG-potentiated—does not significantly influence the type of response, when age-adjusted. Vagal hyperactivity dominates in younger patients, older patients show tendency to vasodepression.

A structured four-step bedside algorithm, named SponTAneous Nystagmus, Direction, head Impulse test, standiNG (STANDING), has been proposed to differentiate central from peripheral acute vestibulopathy in the Emergency Department (ED). We aimed to evaluate the effective application of STANDING in the management of vertigo in the ED and to define its role in deciding the patient’s pathway after discharge. We retrospectively analysed data from 131 consecutive patients (65% female, mean age 56) undergoing ED visits for a vertigo complaint between April and May 2016. Our study showed that the STANDING algorithm is underused, being performed only in the 18% of patients. The positivity of the STANDING did not influence the choice of the following pathway (e.g. outpatient fast track or discharge). Moreover, a small percentage of patients had a non-audiological diagnosis (mainly presyncope), for which no defined pathways were yet foreseen. Our study emphasized the need for continuous updating with appropriate training courses and the importance of a multidisciplinary assessment of vertigo in the ED.

Serum uric acid (SUA) levels discriminating across the different strata of cardiovascular risk is still unknown. By utilizing a large population-based database, we assessed the threshold of SUA that increases the risk of total mortality and cardiovascular mortality (CVM). The URRAH study (Uric Acid Right for Heart Health) is a multicentre retrospective, observational study, which collected data from several large population-based longitudinal studies in Italy and subjects recruited in the hypertension clinics of the Italian Society of Hypertension. Total mortality was defined as mortality for any cause, CVM as death due to fatal myocardial infarction, stroke, sudden cardiac death, or heart failure. A total of 22 714 subjects were included in the analysis. Multivariate Cox regression analyses identified an independent association between SUA and total mortality (hazard ratio, 1.53 [95% CI, 1.21–1.93]) or CVM (hazard ratio, 2.08 [95% CI, 1.146–2.97]; P P

Optimal blood pressure (BP) control can prevent major adverse health events, but target values are still controversial, especially in older patients with comorbidities, frailty and disability. To evaluate mortality according to BP values in a cohort of older adults enrolled in the Fiesole Misurata Study, after a 6-year follow-up. Living status as of December 31, 2016 was obtained in 385 subjects participating in the Fiesole Misurata Study. Patients' characteristics were analysed to detect predictors of mortality. At baseline, all participants had undergone office BP measurement and a comprehensive geriatric assessment. After a 6-year follow-up, 97 participants had died (25.2%). After adjustment for comorbidities and comprehensive geriatric assessment, mortality was significantly lower for SBP 140–159 mmHg as compared with 120–139 mmHg (HR 0.54, 95% CI 0.33–0.89). This result was also confirmed in patients aged 75 + (HR 0.49, 95% CI 0.29–0.85), and in those with disability (HR 0.36, 95% CI 0.15–0.86) or taking antihypertensive medications (HR 0.49, 95% CI 0.28–0.86). An intensive BP control may lead to greater harm than benefit in older adults. Indeed, the European guidelines recommend caution in BP lowering in older patients, especially if functionally compromised, to minimize the risk of hypotension-related adverse events. After a 6-year follow-up, mortality risk was lower in participants with SBP 140–159 mmHg as compared with SBP 120–139 mmHg, in the overall population and in the subgroups of subjects aged 75 + , with a disability or taking anti-hypertensive medications.

Background Cardiac pacing is the treatment of choice for cardioinhibitory carotid sinus syndrome (CSS), but syncope recurrence occurs in up to 20% of patients within 3 years. The present study aims at assessing incidence and identifying predictors of syncope recurrence in patients receiving pacing therapy for CSS. Methods The Syncope Clinics of two large regional hospitals in Northern Italy, both following European Syncope Guidelines, combined to perform this study. Retrospective analysis of 3127 consecutive patients undergoing carotid sinus massage (CSM) was performed 2004–2014. Ten-second supine and standing CSM was systematically assessed in patients aged >40 years with suspected reflex syncope as part of the initial evaluation. Syncope recurrence was investigated in those paced for CSS having >6 months' available follow-up. Data were collected from clinical records and patient interviews. Results CSS was diagnosed in 261 patients (8.3%). Pacemakers were implanted in 158, with follow-up data available in 112: 19 (17%) experienced 73 syncope recurrences during a mean follow-up of 89 ± 42 months, yielding an incidence of 0.5 episodes per patient/year. Prodrome, predisposing situations preceding syncope and chronic nitrate therapy were more frequent in patients reporting recurrence. Prodrome and predisposing situations remained independent predictors of post-implantation recurrence on multivariable analysis. Conclusions CSS is a frequent cause of syncope, if CSM is performed during the initial evaluation. Most patients treated by pacing remain asymptomatic during long-term follow-up. In those who have recurrence, its incidence is very low. Prodrome and predisposing situations are predictors of post-implantation recurrence, suggesting presence of hypotensive susceptibility.

Background Psychogenic pseudosyncope (PPS) is a conversion disorder that often mimics syncope, is commonly referred to cardiology clinics and accounts for a large proportion of patients admitted with “unexplained syncope”. Unlike syncope, PPS is characterized by normal blood pressure (BP) and heart rate (HR) values at TLOC inferring the absence of cerebral hypoperfusion. The current gold standard for the diagnosis of PPS is the reproduction of patients' symptoms during a head-up tilt test (HUTT) with concurrent electroencephalogram (EEG) monitoring showing normal haemodynamic and brainwave measurements. However, EEG is time consuming, resource intensive and many syncope units lack ready access, thereby solely relying on absence of peripheral haemodynamic changes to diagnose PPS. Purpose Near-infrared spectroscopy (NIRS) is a non-invasive technology used for continuous monitoring of cerebral oxygenation. Measuring adequacy of tissue oxygenation is an appropriate surrogate for cerebral perfusion. In this study, we present a case series of patients for whom the diagnosis of PPS was confirmed by NIRS during TLOC. We propose use of NIRS in routine clinical assessment of suspected PPS. Methods We describe nine consecutive patients with suspected PPS referred to a dedicated syncope unit for investigation of recurrent unexplained syncope. All patients underwent evaluation in accordance with European Society of Cardiology guidelines including HUTT. Continuous beat-to-beat BP and HR measurements were recorded using finger plethysmography. In addition, continuous NIRS-derived tissue saturation index (TSI) - a measure of percentage oxygenation - was recorded using an optical sensor applied to the left lateral forehead to assess cerebral perfusion. Absolute values of BP, HR and TSI at baseline, time of first symptom onset, presyncope and apparent TLOC were recorded. The evaluation was diagnostic for PPS when apparent TLOC occurred in the absence of typical haemodynamic or cerebral perfusion changes. Results The median age was 35 years (range 14–54). Clinical features were consistent with those previously described in PPS literature - female preponderance, comorbid psychiatric diagnosis, frequent attack history, with prolonged TLOC and eyes closed during events. During HUTT, all patients experienced an apparent TLOC which they recognised as reproductive of typical events. BP and HR measurements increased significantly at time of TLOC. There was no significant change in TSI at any of the time points throughout HUTT. (Figure 1 shows averaged absolute values of systolic and diastolic BP, HR and TSI with median values represented by thickened lines.) Figure 1. Measurements during HUTT Conclusion NIRS is readily available, easily accessible and provides an appropriate surrogate measure of cerebral perfusion during HUTT. We propose that HUTT incorporating concurrent NIRS monitoring will enhance diagnostic yield and patient management providing important biofeedback.

Older people taking benzodiazepines (BDZs) have higher risk of falling, which is mainly attributed to cognitive and psychomotor effects. BDZs may also have hypotensive effects. We investigated the association between BDZs and orthostatic blood pressure behaviour in older people.We retrospectively analysed data from an outpatient clinic where people aged 60 or older underwent a geriatric assessment. Non-invasive beat-to-beat orthostatic systolic blood pressure (SBP) was assessed at regular time intervals before and after an active stand test. We compared clinical characteristics between BDZs users and non-users and also investigated if BDZs use was an independent predictor of baseline SBP. Factors associated with SBP change were investigated using a repeated measures general linear model.Of 538 participants (67.7% female, mean age 72.7), 33 (6.1%) reported regular BDZs use. BDZ users had lower baseline SBP (149 versus 161 mmHg, P 0.05). Multiple linear regression confirmed BDZs use as independent predictor of baseline SBP in N = =538. At 10 s post-stand, the SBP difference between BDZs use groups became maximum (21 mmHg); at this point, SBP still seemed to be decreasing in BDZ-users, whereas in controls it seemed to be recovering. After adjustment (age, sex, hypertension, frailty, comorbidity, antihypertensives), BDZs were associated with greater SBP reduction between baseline and 10 s post-stand (P 0.05).Older people taking BDZs may have a higher risk of orthostatic hypotension, perhaps due to an exaggerated immediate BP drop. This adds to other BDZ-related falls risks. BDZs should be avoided in older people at risk of falling.