Clinical features and response at head-up tilt test of patients with situational syncope.

OBJECTIVE: The study compared clinical characteristics and response at head-up tilt test (HUTT) between situational (SS) and vasovagal syncope (VVS). METHODS: Consecutive patients who underwent nitroglycerin-potentiated HUTT were retrospectively dichotomised into two groups: those with a history of SS and those with a history of VVS. The patients with SS were further subdivided into patients with SS alone and with SS and at least one episode of VVS. RESULTS: 1285 patients were enrolled: 246 (19.1%) had SS (SS alone in 121 and SS+VVS in 125). Patients with SS were older (48.8±20.0 vs 44.4±19.1, p=0.007) and more frequently male (57.3% vs 47.7%, p=0.001). At multivariable analysis, smoking habit (OR 2.28; p<0.0001), history of traumatic syncope (OR 2.29; p=0.0001) and ACE inhibitors/angiotensin II receptor blockers (OR 4.74; p<0.0001) were independently associated with SS. HUTT was positive in 175 (71.1%) patients with SS and in 737 (70.9%) patients with VVS (p=0.9). Patients with SS showed more mixed (42.3% vs 32.0%, p=0.002) and vasodepressor forms (10.6% vs 6.1%, p=0.01) and less cardioinhibitory responses compared with others (18.3% vs 32.8%, p<0.0001). CONCLUSIONS: Compared with VVS, patients with SS have different clinical characteristics and a higher prevalence of hypotensive drugs leading to hypotensive susceptibility. The positivity rate of HUTT is high and similar to that of VVS, although patients with SS show a higher prevalence of hypotensive responses.

Short-duration head-up tilt test potentiated with sublingual nitroglycerin in suspected vasovagal syncope: the fast Italian protocol.

BACKGROUND: The traditional nitroglycerin (NTG) head-up tilt test (HUTT) is time-consuming and the test duration is a barrier to widespread utilization in clinical practice. It was hypothesized that a short-duration protocol is not inferior to the traditional protocol regarding the positivity rate and has a similar distribution of hemodynamic response. METHODS AND RESULTS: Patients undergoing HUTT were randomized 1:1 to a 10 min passive phase plus a 10 min 0.3 mg NTG if the passive phase was negative (Fast) or to a 20 min passive phase plus a 15 min 0.3 mg NTG if the passive phase was negative (Traditional). A sample size of 277 patients for each group achieved 80% power to detect an expected difference of 0% with a non-inferiority margin of -10% using a one-sided t-test and assuming a significant level alpha of 0.025. A total of 554 consecutive patients (mean age 46.6 ± 19.3 years, 47.6% males) undergoing HUTT for suspected vasovagal syncope were randomly assigned to the Fast (n = 277) or Traditional (n = 277) protocol. A positive response was defined as the induction of syncope in presence of hypotension/bradycardia, and was observed in 167 (60.3%) patients with Fast and in 162 (58.5%) patients with the Traditional protocol. There was a trend of lesser vasodepressor response (14.8% Fast vs. 20.6% Traditional) which was significant during the passive phase (P = 0.01). CONCLUSION: The diagnostic value of the Fast HUTT protocol is similar to that of the Traditional protocol and therefore the Fast protocol can be used instead of the Traditional protocol.

The clinical presentation of syncope influences the head-up tilt test responses.

INTRODUCTION: Little is still known about the positivity rate of nitroglycerin (NTG) potentiated head-up tilt test (HUTT) according to the history-based clinical features of syncope. The study aimed to compare the HUTT positivity rate and type of responses in patients with classical and non-classical vasovagal syncope (VVS). MATERIALS AND METHODS: We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for VVS. The study population was dichotomized into classical and non-classical VVS. RESULTS: A total of 1285 VVS patients (45± 19.1 years; 49.6% male) were enrolled: 627 (48.8%) had a history of classical VVS and 658 (51.2%) of non-classical VVS. HUTT was positive in 866 (67.4%) patients. The positivity rate was significantly higher in patients with classical compared to those with non-classical VVS (81.5% vs 54%; P< 0.0001). Cardioinhibitory response showed similar total positivity rate (27.6% vs 31%; P= 0.17), but higher relative prevalence among positive tests (57.7% vs 33.9%, P< 0.0001) in patients with non-classical VVS. At multivariable analysis, classical reflex syncope, male sex, history of traumatic syncope and use of diuretics were independent predictors of HUTT positivity. CONCLUSION: The clinical presentation of syncope influences the overall HUTT positivity rate and the type of responses. Cardioinhibitory response and traumatic syncope are more likely in patients with non-classical VVS.

Cardioinhibitory syncope with asystole during nitroglycerin potentiated head up tilt test: prevalence and clinical predictors.

AIMS: The aim of our study was to evaluate the prevalence and clinical predictors of cardioinhibitory (CI) responses with asystole at the nitroglycerin (NTG)-potentiated head-up tilt test (HUTT) in patients with a history of syncope admitted to a tertiary referral syncope unit. METHODS: We retrospectively evaluated all consecutive patients who underwent NTG-potentiated HUTT for suspected reflex syncope at our institution from March 1 2017 to May 1 2020. The prevalence of HUTT-induced CI syncope was assessed. Univariate and multivariate analyses were performed to test the association of asystolic response to HUTT with a set of clinical covariates. RESULTS: We enrolled 1285 patients (45 ± 19.1 years; 49.6% male); 368 (28.6%) showed HUTT-induced CI response with asystole. A multivariate analysis revealed that the following factors were independently associated with HUTT-induced CI syncope: male sex (OR 1.48; ConInt 1.14-1.92; P = 0.003), smoking (OR 2.22; ConInt 1.56-3.115; P < 0.001), traumatic syncope (OR: 2.81; ConInt 1.79-4.42; P < 0.001), situational syncope (OR 0.45; ConInt 0.27-0.73; P = 0.002), and the use of diuretics (OR 9.94; ConInt 3.83-25.76; P < 0.001). CONCLUSIONS: The cardioinhibitory syncope with asystole induced by NTG-potentiated HUTT is more frequent than previously reported. The male gender, smoking habit, history of traumatic syncope, and use of diuretics were independent predictors of HUTT-induced CI responses. Conversely, the history of situational syncope seems to reduce this probability.

Pharmacokinetics of Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Extreme Obesity.

PURPOSE: Direct oral anticoagulants (DOACs) are recommended in preference to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF) eligible for oral anticoagulation therapy; however, data and clinical experiences supporting the use of DOACs in patients with a body mass index ≥40 kg/m2 or weight >120 kg remain limited. The aim of this study was to evaluate the pharmacokinetic properties of DOACs in patients with AF and extreme obesity. METHODS: We enrolled all consecutive patients with AF and extreme obesity undergoing treatment with DOACs followed up at Monaldi Hospital, Naples, Italy. To determine peak plasma and trough levels of DOACs, plasma samples were collected at 2nd, 4th, 6th, and 12th hours from the last dose intake in patients receiving apixaban and dabigatran and at the 2nd, 4th, 6th, and 24th hours in those receiving edoxaban and rivaroxaban. The DOACs' peak and trough plasma levels obtained from our study population were compared with those sourced from pharmacokinetic studies among patients without obesity, defined as a normal reference range in the literature. If at least 1 peak or trough plasma level was found ​​below or above the normal reference ranges, the patients were classified as having out-of-range DOAC plasma levels. Study population was then divided into in-range and out-of-range groups. Baseline characteristics, including DOAC treatment, were compared between the 2 groups. Univariate and multivariate logistic regression analysis were performed to identify baseline variables associated with DOACs' plasma concentration out of the expected range. FINDINGS: A total of 58 patients (mean [SD] age, 70.93 [8.73] years; 40% female) with extreme obesity (mean [SD] body mass index. 44.43 [3.54] kg/m2) and AF while undergoing DOAC treatment were included in the present study. In 9 patients (15.5 %), the DOAC plasma concentrations were out of the expected ranges (out-of-range group);, indicating a greater likelihood of edoxaban 30 mg treatment (33% vs 2%; P < 0.01) and inappropriate DOAC underdosing (56% vs 4%; P < 0.005) compared with the in-range group. According to the multivariate logistic analysis (P = 0.0011), the inappropriate DOAC underdosing (hazard ratio = 29.37; P = 0.0002) was an independent predictor of DOAC plasma levels out of the expected ranges. IMPLICATIONS: Patients with extreme obesity and AF who were receiving DOAC therapy had DOAC plasma concentrations in the expected range. The inappropriate DOAC underdosing seems to be the only independent clinical factor associated with a plasma concentration of the drug out of the expected range.

Edoxaban in elderly patient with morbid obesity and atrial fibrillation: the role of plasma levels evaluation for selecting the appropriate dose.

We present the case of a 80-year-old man with atrial fibrillation, morbid obesity (weight 123 kg, height 167 cm, BMI 44.1), high clearance of creatinine and pharmacological polytherapy, in which the serial determinations of edoxaban plasma levels help us to choose the appropriate dose.