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Giuseppe Pasqualetti,1 Valeria Calsolaro,1 Giacomo Bini,1 Umberto Dell’Agnello,1 Marco Tuccori,2 Alessandra Marino,2 Alice Capogrosso-Sansone,2 Martina Rafanelli,3 Massimo Santini,4 Eugenio Orsitto,4 Andrea Ungar,3 Corrado Blandizzi,2 Fabio Monzani1 On behalf of the ANCESTRAL-ED study group 1Geriatrics Unit, 2Pharmacology Unit, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, 3Syncope Unit, Geriatric and Intensive Care Medicine, AOU Careggi and University of Florence, Florence, 4Emergency Department, University Hospital of Pisa, Pisa, Italy Abstract: It is difficult to distinguish unexplained falls (UFs) from accidental falls (AFs) or syncope in older people. This study was designed to compare patients referred to the emergency department (ED) for AFs, UFs or syncope. Data from a longitudinal study on adverse drug events diagnosed at the ED (ANCESTRAL-ED) in older people were analyzed in order to select cases of AF, syncope, or UF. A total of 724 patients (median age: 81.0 [65–105] years, 66.3% female) were consecutively admitted to the ED (403 AF, 210 syncope, and 111 UF). The number of psychotropic drugs was the only significant difference in patients with AF versus those with UF (odds ratio [OR] 1.44; 95% confidence interval 1.17–1.77). When comparing AF with syncope, female gender, musculoskeletal diseases, dementia, and systolic blood pressure >110 mmHg emerged as significantly associated with AF (OR 0.40 [0.27–0.58], 0.40 [0.24–0.68], 0.35 [0.14–0.82], and 0.31 [0.20–0.49], respectively), while valvulopathy and the number of antihypertensive drugs were significantly related to syncope (OR 2.51 [1.07–5.90] and 1.24 [1.07–1.44], respectively). Upon comparison of UF and syncope, the number of central nervous system drugs, female gender, musculoskeletal diseases, and SBP >110 mmHg were associated with UF (OR 0.65 [0.50–0.84], 0.52 [0.30–0.89], 0.40 [0.20–0.77], and 0.26 [0.13–0.55]), respectively. These results indicate specific differences, in terms of demographics, medical/pharmacological history, and vital signs, among older patients admitted to the ED for AF and syncope. UF was associated with higher use of psychotropic drugs than AF. Our findings could be helpful in supporting a proper diagnostic process when evaluating older patients after a fall. Keywords: older people, frailty, fall, accidental fall, syncope

We assessed the capability of an integrated multisensory patch-type monitor (RootiRx®) in detecting episodes of reflex (pre)syncope induced by tilt table test (TTT). Firstly, we performed an intrapatient comparison of cuffless systolic blood pressure (SBP), R-R interval (RRI) and variability (power spectrum analysis) obtained by means of the RootiRx® with those obtained with conventional methods (CONV) with validated finger pressure devices at baseline in supine position and repeatedly during TTT in 32 patients affected by likely reflex syncope. Secondly, the LF/HF values obtained with RootiRx® during TTT were analyzed in 50 syncope patients. Compared with baseline supine recordings, during TTT a decrement of median SBP was observed with CONV (-53.5 mmHg) but not with RootiRx® ®(-1 mmHg). Conversely, RRI reduction (CONV: 102 ms; RootiRx®: 127 ms) and RRI Low Frequency/High Frequency powers ratio (LF/HF) increase (CONV: 1.6; RootiRx®: 2.5) were similar. The concordance was good for RRI (0.97 [95% CI 0.96-0.98]) and fair for LF/HF ratio (0.69 [95% CI 0.46-0.83]). During the first 5 min of TTT the LF/HF ratio was higher in patients who later developed syncope than in no-syncope patients. This ratio was significantly different among patients with syncope, presyncope or without symptoms at the time of syncope (p value = 0.02). In conclusion, cuffless RootiRx® was unable to detect rapid drops of SBP occurring during impending reflex syncope and thus cannot be used as a diagnostic tool for hypotensive syncope. On the other hand, RRI mean values and LF/HF power ratios obtained with RootiRx® were consistent with those simultaneously obtained using conventional methods., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Martina Rafanelli, Alessandro Morrione, Annalisa Landi, Emilia Ruffolo, Valentina M Chisciotti, Maria A Brunetti, Niccolò Marchionni, Andrea Ungar Syncope Unit, Cardiology and Geriatric Medicine, University of Florence and Azienda Ospedaliero-Universitaria Careggi, Florence, Italy Background: The incidence of syncope increases in individuals over the age of 70 years, but data about this condition in the elderly are limited. Little is known about tilt testing (TT), carotid sinus massage (CSM), or supine and upright blood pressure measurement related to age or about patients with complex diagnoses, for example, those with a double diagnosis, ie, positivity in two of these three tests. Methods: A total of 873 consecutive patients of mean age 66.5±18 years underwent TT, CSM, and blood pressure measurement in the supine and upright positions according to the European Society of Cardiology guidelines on syncope.1 Neuroautonomic evaluation was performed if the first-line evaluation (clinical history, physical examination, electrocardiogram) was suggestive of neurally mediated syncope, or if the first-line evaluation was suggestive of cardiac syncope but this diagnosis was excluded after specific diagnostic tests according to European Society of Cardiology guidelines on syncope, or if certain or suspected diagnostic criteria were not present after the first-line evaluation. Results: A diagnosis was reached in 64.3% of cases. TT was diagnostic in 50.4% of cases, CSM was diagnostic in 11.8% of cases, and orthostatic hypotension was present in 19.9% of cases. Predictors of a positive tilt test were prodromal symptoms and typical situational syncope. Increased age and a pathologic electrocardiogram were predictors of carotid sinus syndrome. Varicose veins and alpha-receptor blockers, nitrates, and benzodiazepines were associated with orthostatic hypotension. Twenty-three percent of the patients had a complex diagnosis. The most frequent association was between vasovagal syncope and orthostatic hypotension (15.8%); 42.9% of patients aged 80 years or older had a complex diagnosis, for which age was the strongest predictor. Conclusion: Neuroautonomic evaluation is useful in older patients with unexplained syncope after the initial evaluation. A complex neurally mediated diagnosis is frequent in older people. Our results suggest that complete neuroautonomic evaluation should be done particularly in older patients. Keywords: syncope, elderly, tilt testing, carotid sinus massage, blood pressure, neurally mediated diagnosis

: Managing hypertension in syncope patients requires the accurate balancing of hypotensive and cardiovascular risks. On the basis of the available literature, this study analyses the complex inter-relationship between these clinical problems and presents an algorithm strategy to guide hypertension management in patients affected by syncope episodes. A SBP target of 120 mmHg is recommended in patients with a low syncope risk and a high cardiovascular risk. In patients with a high syncope risk and a low cardiovascular risk, and in older (70+) frail individuals, a less intensive treatment is advisable, targeting SBP of 140 mmHg. SBP values up to 160 mmHg can be tolerated in severe frailty or disability.Patients with hypertension and syncope may benefit from team-based care by a 'Blood Pressure Team' including experts on hypertension and syncope and a geriatrician. The team should carry out a multidimensional assessment to balance syncope and cardiovascular risk and develop therapeutic strategies customized to individuals' frailty and functional status.

Background: In patients with unexplained syncope, bifascicular block (BFB) is considered associated with syncope due to either heart block or sinus arrest. Immediate or delayed pacemaker (PM) implantation after ECG documentation of syncopal recurrence by means of implantable cardiac monitors (ICM) is still debated. We aimed to assess the incidence of recurrent syncope and guideline-based PM implantation in patients with syncope and BFB implanted with ICM., Methods: Consecutive patients with syncope and BFB followed at two tertiary care syncope units and implanted with ICM from 2012 to 2020 were retrospectively reviewed. Only patients with ≥2 clinical visits and ≥ 18 years of age were included. Incidence of a Class I indication for PM implantation was the primary outcome., Results: Of 635 syncope patients implanted with an ICM, 55 (8.7%) had a BFB and were included. Median age at implantation was 75 [interquartile range, IQR:64-81] years, and 28(49.1%) were women. At 26 [IQR:12-41] months follow-up, 20 (36.3%,16.3%/year) patients experienced syncope: in 6(10.9%) patients syncope was classified 'arrhythmic' with a higher prevalence in older individuals (p = 0.048). PM implantation (N = 14,25.5%) was more frequent in patients ≥75 years (p = 0.024). At survival analysis, patients ≥75 years were at highest risk of arrhythmic syncope and guideline directed PM implantation (Hazard Ratio: 4.5, 95% Confidence Intervals 1.5-13.3)., Conclusions: Most older patients with syncope who received an ICM did not have events during follow-up. One-in-three experienced syncope, and an even smaller number had an arrhythmic syncope with indication for PM implantation. Older age was strongly associated with PM implantation., (Copyright © 2022 Elsevier B.V. All rights reserved.)

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 (<110, 100, 90, 80 mmHg) were assessed. Findings were validated in an independent sample. In the derivation sample, daytime SBP drops were significantly more common in 158 syncope patients than 329 controls. One or more daytime drops <90 mmHg achieved 91% specificity and 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 sample of 164 syncope patients and 164 controls: one or more daytime SBP drops <90 mmHg achieved 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 2.6, P < 0.001)., 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., Competing Interests: Conflicts of interests: R.S. declares the following potential conflicts of interest: consulting fees from Medtronic Inc (unrelated to present work); payment for expert testimony in medico-legal cases in UK (related to syncope but unrelated to this work); member of clinical events committee for the BioSync study (published in 2021 in European Heart Journal); Secretary to the Executive Board of World Society of Arrhythmias; private shareholder receiving only dividends from Boston Scientific Corp and Edwards Lifesciences Corp. A.F. has received speaker fees from Medtronic Inc., Biotronik, and Bristol-Myers Squibb, and is consultant to Medtronic Inc, and Argenx BV. The other authors declare no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Cardiology.)

Background We assessed the reliability and feasibility of blood pressure (BP) measurements by means of a new wearable watch-type BP monitor (HeartGuide) in detecting episodes of hypotensive (pre)syncope induced by tilt table test. Methods and Results An intrapatient comparison between systolic BP (SBP) measured by means of the HeartGuide device and noninvasive finger beat-to-beat BP monitoring was undertaken both at baseline in supine position and repeatedly during tilt table test in patients evaluated for reflex syncope. Intrapatient fall of systolic BP from baseline was measured. Eighty-one patients (mean age, 61±19 years; 46 women) were included. Overall, HeartGuide was able to yield BP values at the time of BP nadir in 58 (72%) patients (average HeartGuide SBP 102±18 mm Hg, versus finger SBP 101±19 mm Hg). Compared with baseline, the maximum SBP decrease was on average -28.5±27.8 and -30.3±33.9 mm Hg respectively (Lin's concordance correlation coefficient=0.78, r =0.79, P =0.001). In the subgroup of 38 patients with tilt table test induced (pre)syncope, the average HeartGuide SBP during symptoms was 97±16 mm Hg, and the finger SBP was 94±18 mm Hg. Compared with baseline, the maximum SBP decrease was on average -35.2±29.3 and -43.3±31.8 mm Hg, respectively (Lin's concordance correlation coefficient=0.83, r =0.87, P =0.001). Conclusions Our data indicate that the HeartGuide BP monitor can detect low BP during presyncope and that its measure of SBP change is consistent with that simultaneously obtained through continuous BP monitoring, despite some intrapatient variability. Thus, this device might be useful in determining the hypotensive nature of spontaneous (pre)syncopal symptoms, a possibility that should be verified by field studies.

Falls are a geriatric syndrome affecting mortality, morbidity, and institutionalization. Falls are also the leading cause of unintentional injury and a common emergency department presentation. Physical and psychological issues may develop after falling, leading to increase in dependency and disability and their relative costs. The pathogenesis of falls is multi-factorial, being indeed the result of the interaction between increased individual susceptibility, high risk activities and environmental hazards. The patient should be evaluated for gait, standing balance, mobility, muscle weakness, cognitive status, osteoporosis risk, sensorial impairment, urinary incontinence, functional status, and for possible residential environmental hazards. It is also mandatory to obtain a full report of the circumstances and a careful therapeutic recognition. However not all falls are explainable. Indeed, retrograde amnesia and the frequent absence of a witness complicate history collection of falls in older adults. In this case, "the management of unexplained falls should be the same as that for unexplained syncope" as stated by the latest version of the European Society of Cardiology guidelines on syncope. In this context, the investigation of the cardiovascular autonomic nervous system and the use of implantable loop recorder have an increasing role. The present paper addresses the diagnostic approach to falls in older adults through a comprehensive multifactorial risk assessment and examines evidence and gaps on fall prevention strategies.

Objective: To compare one-year mortality risk associated with syncope and unexplained fall in older adults with dementia., Methods: 522 patients (aged >65 years) with dementia and history of transient loss of consciousness and/or unexplained falls were evaluated. The diagnosis of syncope was based on European Society of Cardiology guidelines. A "Syncopal Fall" was defined in patients with an initial clinical presentation of unexplained fall, but a final diagnosis of syncope after complete assessment. A "Truly Unexplained Fall" was defined in patients with an initial clinical presentation of unexplained fall, in whom a diagnosis of syncope had been excluded after the diagnostic work-up. One-year follow-up was assessed by phone interview., Results: Follow-up data were available for 501 participants (mean age 83 ± 6 years, 65% female). After a mean follow-up of 324 ± 93 days, death from any cause was reported in 188 participants (24%). Advanced age, male sex, cognitive and functional impairment were associated with a higher mortality rate. Patients with "Truly Unexplained Falls" had a higher mortality risk compared with syncope and "Syncopal Fall". A diagnosis of "Truly Unexplained Falls" remained an independent predictor of one-year all-cause mortality in multivariate model., Conclusions: We propose the novel diagnostic category of "Truly Unexplained Fall", resulting from the application of syncope guidelines to subjects with unexplained falls. This condition in older adults with dementia is a predictor of one-year all-cause mortality. For this new high risk profile, we advice a comprehensive geriatric assessment focused on risk factors for fall, aimed at a possible improvement of prognosis., (Copyright © 2022. Published by Elsevier B.V.)

Background: Implantable cardiac monitor (ICM) revealed subclinical atrial fibrillation (SCAF) in up to 30% of cryptogenic stroke (CS) patients in randomized trials. However, real world data are limited., Objectives: We investigated SCAF occurrence, treatments, clinical outcomes and predictors of SCAF in a multicenter real-world population subjected to ICM after CS., Methods: From September 2016 to November 2019, 20 Italian centers collected data of consecutive patients receiving ICM after CS and followed with remote and outpatient follow-up according to clinical practice. All device-detected AF events were confirmed by the cardiologist to diagnose SCAF., Results: ICM was implanted in 334 CS patients (mean age±SD 67.4±11.5 years, 129 (38.6%) females, 242 (76.1%) with CHA 2 DS 2 -VASC score≥4). During a follow-up of 23.6 (IQR 14.6-31.5) months, SCAF was diagnosed in 92 (27.5%) patients. First episode was asymptomatic in 81 (88.1%). SCAF daily burden ≥5 minutes was 22.0%, 24.1% and 31.5% at 6, 12, and 24 months after ICM implantation. Median time to first day with AF was 60 (IQR 18-140) days. Female gender, age>69 years, PR interval>160 ms and cortical-subcortical infarct type at enrolment were independently associated with an increased risk of SCAF., Conclusions: In a real-world population, ICM detected SCAF in more than a quarter of CS patients. This experience confirms the relevance of implanting CS patients, for maximizing the possibilities to detect AF, following failure of Holter monitoring, according to guidelines. However, there is need to demonstrate that shift to oral anticoagulation following SCAF detection is associated with reduced risk of recurrent stroke., (Copyright © 2021. Published by Elsevier B.V.)

Aim of this study was to explore whether differences in resting hemodynamic parameters may be associated with tilt test results in unexplained syncope. We analyzed age, gender, systolic (SBP), diastolic blood pressure (DBP) and heart rate (HR) by merging three large databases of patients considered likely to be of vasovagal reflex etiology, comparing patients who had tilt-induced reflex response with those who did not. Tilt-induced reflex response was defined as spontaneous symptom reproduction with characteristic hypotension and bradycardia. Relationship of demographics and baseline supine BP to tilt-test were assessed using logistic regression models. Individual records of 5236 patients (45% males; mean age: 60 ± 22 years; 32% prescribed antihypertensive therapy) were analyzed. Tilt-positive (n = 3129, 60%) vs tilt-negative patients had lower SBP (127.2 ± 17.9 vs 129.7 ± 18.0 mmHg, p < 0.001), DBP (76.2 ± 11.5 vs 77.7 ± 11.7 mmHg, p < 0.001) and HR (68.0 ± 11.5 vs 70.5 ± 12.5 bpm, p < 0.001). In multivariable analyses, tilt-test positivity was independently associated with younger age (Odds ratio (OR) per 10 years:1.04; 95% confidence interval (CI), 1.01-1.07, p = 0.014), SBP ≤ 128 mmHg (OR:1.27; 95%CI, 1.11-1.44, p < 0.001), HR ≤ 69 bpm (OR:1.32; 95%CI, 1.17-1.50, p < 0.001), and absence of hypertension (OR:1.58; 95%CI, 1.38-1.81, p < 0.001). In conclusion, among patients with suspected reflex syncope, younger age, lower blood pressure and lower heart rate are associated with positive tilt-test result., (© 2021. The Author(s).)

The aim of our study was to evaluate the impact of the COVID-19 outbreak on Syncope Units (SUs) Activities in Italy. Methods: Data about types of SU activities and admissions were obtained from 10 SUs throughout Italy, certified by the Italian Multidisciplinary Working Group on Syncope (GIMSI), from 10 March 2020 to 31 December 2020 and compared with the same time frame in 2019. Results: A remarkable reduction in overall non-invasive diagnostic tests (-67%; p < 0.001) and cardiac invasive procedure. Elective cardiac pacing procedures disclosed a significant decrease (-62.7%; p < 0.001); conversely, the decrease of urgent procedures was not significant (-50%; p = 0.08). There was a significantly increased rate of patients who underwent both telemedicine follow-up visits (+225%, p < 0.001) and cardiac implantable electronic devices (CIEDs) remote monitoring follow-up visits (+100%; p < 0.001). Conclusion: The COVID-19 outbreak was associated with a remarkable decrease in all clinical activities of Syncope Units in Italy, including both non-invasive tests and cardiac invasive procedures; conversely, a significant increase in telehealth activities was shown.

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.

In this paper, we define an intersection matrix for enriching the semantics of the topological relationships between a directed polyline and a polygon. In particular, we propose the $$\mathcal {DLP}$$ -intersection matrix which enables us to model the origin and destination points, as well as the right- and left-hand sides of the directed polyline. This matrix overcomes the limitation of the well-known DE-9 IM, because it allows the representation of the different dimensions of the intersection results at the same time. Accordingly, the geo-operators have been revised and extended in order to address the notions of right- and left-hand sides of a directed polyline, as well as additional notions related to the orientation of the polyline. The $$\mathcal {DLP}$$ -intersection matrix has been implemented by extending the Java Topology Suite methods in order to address the new geo-operators based on the notion of orientation. [ABSTRACT FROM AUTHOR]

Hypertension management is challenging in frail older adults. The balance between treatment risks and benefits may be difficult to achieve due to an increased vulnerability to treatment-related adverse events, and limited evidence is available to support clinical decisions. The effects of frailty on blood pressure are unclear, as well as its impact on antihypertensive treatment benefits. Appropriate blood pressure targets in frail patients are debated and the frailty measure which best inform clinical decisions in hypertensive patients has yet to be identified. Therefore, hypertension management in frail older adults still represents a 'gap in evidence'. Knowledge of currently available literature is a fundamental prerequisite to develop future research and may help to implement frailty assessment and improve hypertension management in this vulnerable population. Given these premises, we present a narrative review illustrating the most relevant issues that are a matter of debate and that should be addressed in future studies., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Muscle mass is frequently reduced in older patients experiencing injurious falls and may further reduce during hospitalization for bone fracture. In these patients, renal function may be overestimated, because it is usually calculated using serum creatinine, which is strictly related to muscle mass. We evaluated if creatinine levels change during hospitalization in older patients with fracture. We also assessed the role of cystatin C as a more appropriate marker of renal function, comparing estimated glomerular filtration rate (eGFR) according to different formulas based on creatinine and/or cystatin C levels., Methods: Patients aged 65+ years, consecutively hospitalized for fracture, were enrolled in a prospective cohort study. Creatinine and cystatin C levels were measured at baseline and in the post-operative period; eGFR was calculated using six equations based on creatinine and/or cystatin C., Results: 425 patients were enrolled (mean age 84 years, mean creatinine 0.97 mg/dL, mean cystatin C 1.53 mg/L). Creatinine levels significantly decreased after surgery (p<0.001), while cystatin C remained stable. According to creatinine-based formulas, eGFR was < 60 mL/min/1.73 m 2 in 29-30% at baseline and only in 17% participants in the post-operative period. Conversely, according to equations including cystatin C, eGFR was < 60 mL/min/1.73 m 2 in half to three-quarters of the sample at all assessments., Conclusions: In older fractured patients, creatinine levels decline during hospital stay and may possibly overestimate renal function, whereas cystatin C remains stable. Whether cystatin C is a more reliable marker of renal function in this specific population should be further investigated., (Copyright © 2020. Published by Elsevier B.V.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)

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.

Background: 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., Aims: 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., Methods: 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., Results: 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)., Discussion: 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., Conclusions: 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.