Incremental Value of Global Longitudinal Strain for Confirming Heart Failure-Related Symptoms in Severe Aortic Stenosis.

The indications or timing of aortic valve replacement for symptomatic aortic stenosis (AS) are based on a patient's life expectancy and symptoms. However, clinical decision-making may be difficult because symptoms are subjective and cannot be quantitatively assessed and confirmed. This study aimed to evaluate the association between heart failure (HF)-related symptoms and cardiac hemodynamic left ventricular deformations in patients with severe AS using transthoracic echocardiographic assessments of left ventricular global longitudinal strain (LV-GLS). The medical records of patients hospitalized for AS between February 2017 and September 2019 were retrospectively screened. Independent cardiologists analyzed the transthoracic echocardiographic images of a digital echocardiography database. The cohort comprised 177 hospitalized patients with severe AS and no history of HF. The subgroup with HF-related symptoms included 87 patients, whereas that without HF-related symptoms included 90 patients. In 145 patients without atrial fibrillation, the left atrial volume index (LAVI) and LV-GLS were significantly associated with HF-related symptoms (odds ratio 1.033, 95% confidence interval 1.008 to 1.059, p = 0.011 and odds ratio 1.224, 95% confidence interval 1.118 to 1.340, p <0.0001, respectively). Moreover, the combination of brain natriuretic peptide level, LAVI, and LV-GLS showed better diagnostic accuracy than the combination of brain natriuretic peptide level and LAVI (p = 0.005). However, there were no such tendencies in 32 patients with atrial fibrillation. The HF-related symptoms in patients with severe AS were strongly linked to LV-GLS. LV-GLS showed incremental value for confirming HF-related symptoms.

Prognostic significance of the Holter-derived T-wave variability in patients with ventricular tachyarrhythmias complicating acute coronary syndrome-TWIST study.

BACKGROUND: We aimed to investigate the association between ventricular repolarization instability and sustained ventricular tachycardia and ventricular fibrillation (VT/VF) occurring within 48 h (acute-phase VT/VF) after the onset of acute coronary syndrome (ACS) and the prognostic role of repolarization instability and heart rate variability (HRV) after discharge from the hospital. METHODS: We studied 572 ACS patients with a left ventricular ejection fraction >35%. The ventricular repolarization instability was assessed by the beat-to-beat T-wave amplitude variability (TAV) using high-resolution 24-h Holter ECGs recorded at a median of 11 days from the date of admission. We calculated the HRV parameters including the deceleration capacity (DC) and non-Gaussian index calculated on a 25 s timescale (λ25s). The DC and λ25s were dichotomized based on previous studies' thresholds. RESULTS: Acute-phase VT/VF developed in 43 (7.5%) patients. In-hospital mortality was significantly higher among VT/VF patients (4.7% vs. 0.9%, p = .03). An adjusted logistic model showed that the maximum TAV (odds ratio 1.02, 95% confidence interval [CI] 1.00-1.29, p = .04) was associated with acute-phase VT/VF. During a median follow-up period of 2.1 years, 19 (3.3%) patients had cardiac deaths or resuscitated cardiac arrest. Acute-phase VT/VF (p = .12) and TAV (p = .72) were not significant predictors of survival. An age and sex-adjusted Cox model showed that the DC (p < .01), λ25s (p < .01), and emergency coronary intervention (p < .01) were independent predictors. CONCLUSION: T-wave amplitude variability was associated with acute-phase VT/VF, but the TAV was not predictive of survival post-discharge. The DC, λ25s, and emergency coronary intervention were independent predictors of survival.

Mechanisms and implications of mitral regurgitation in patients with severe aortic stenosis who received transcatheter aortic valve replacement.

INTRODUCTION: This study aimed to investigate the mechanisms and clinical implications of mitral regurgitation (MR) in patients with severe aortic stenosis (AS) who received transcatheter aortic valve replacement (TAVR). METHODS: We conducted retrospective echocardiographic analyses at baseline and 6 months after TAVR in 140 patients with symptomatic AS (85 ± 5 years) who underwent TAVR. We defined significant MR as ≥ moderate based on evaluation of transthoracic echocardiography (TTE). RESULTS: There were 48 patients (34%) with preexisting MR at the baseline. Among measured TTE parameters, end-systolic wall stress (ESWS), mitral annulus area, and mitral valve thickening index were independent factors associated with preexisting MR (odds ratio [OR]: 1.013, 95% confidence interval [CI]: 1.005-1.021; OR: 1.740, 95% CI: 1.314-2.376; OR: 2.306, 95% CI: 1.426-3.848; respectively). Six months after TAVR, there were 34 patients with post-existing MR, A history of atrial fibrillation and ESWS after TAVR were independent factors (OR: 3.013, 95% CI: 1.208-7.556; OR: 1.013, 95% CI: 1.000-1.023; respectively). The Kaplan-Meier plot indicated that preexisting MR was a risk factor for heart failure-related events within 1 year of discharge after TAVR (p = .012). CONCLUSIONS: In patients who underwent TAVR for severe AS, preexisting MR was associated with having a thickened mitral valve and large mitral annulus size induced by high ESWS. These patients may have worse prognosis after TAVR and should be closely monitored in the long term.

Utility of open-window mapping for catheter ablation of an accessory pathway in patients with Wolff-Parkinson-White syndrome.

BACKGROUND: Open-window mapping (OWM) is a novel automated mapping method for catheter ablation of an accessory pathway (AP), in which the local signal is annotated with window-of-interest parameters to analyze both atrial and ventricular signals. This study aimed to determine the utility of OWM in visualizing the location and width of APs in patients with Wolff-Parkinson-White syndrome. METHODS: This two-center study enrolled 30 patients (20 males; mean age: 56 years, interquartile range [IQR]: 22-69 years) who underwent high-density OWM with the extended early-meets-late (EEML) algorithm using a 20-electrode, 5-spline catheter (PENTARAY, Biosense Webster). The lower threshold of the EEML was set to adjust the EEML gap to match the propagation mapping, and broad APs were defined as an EEML gap > 1 cm. RESULTS: The median mapping points, mapping time, and lower threshold of the EEML were 2482 (IQR: 1755-4000) points, 23 (IQR: 15-30) min, and 23 (IQR: 18-25), respectively. All 30 APs (24 in the mitral annulus and 6 in the tricuspid annulus) were successfully eliminated. Of these APs, 21 (70%) were eliminated by the first radio frequency (RF) application. OWM revealed broad APs in 11 patients (37%), in four of whom (36%) the first RF application achieved a loss of AP conduction (vs. 90% of patients without broad APs; p = .004). CONCLUSION: OWM facilitates the visualization of the location and width of APs, which may be particularly useful for predicting whether multiple RF applications are required for broad APs.

Echocardiographic score for the screening of cardiac amyloidosis with positive 99m technetium pyrophosphate scintigraphy result.

INTRODUCTION: Speckle-tracking-derived strains in cardiac chambers may provide better solutions for transthyretin amyloid cardiomyopathy (ATTR-CM) screening. This study aimed to evaluate the efficacy of biventricular strain measurements using speckle tracking for screening 99m Tc-pyrophosphate (99m Tc-PYP) scintigraphy-positive cardiomyopathy, which is nearly equivalent to ATTR-CM. METHODS: We performed a retrospective analysis of transthoracic echocardiographic studies using vendor-independent speckle tracking analysis in older patients (≥65 years) who underwent 99m Tc-PYP scintigraphy to evaluate the etiology of suspected ATTR-CM in our institute between January 2019 and December 2022. RESULTS: The entire cohort (n = 89) was divided into two subgroups positive 99m Tc-PYP scan results (n = 34) and negative 99m Tc-PYP scan results (n = 55). In the multivariate analysis, posterior wall thickness (p = .003, odds ratio [OR]:1.48, 95% confidence interval [CI]:1.14 -1.92), left ventricular longitudinal strain apical/basal ratio (LVLSapi/bas) (p = .015, OR: 2.78, 95% CI: 1.23-6.32, and right ventricular longitudinal strain (RVLS) (p = .003, OR: 1.15, 95% CI: 1.05 -1.26) were selected to be the most representative echocardiographic findings in 99m Tc-PYP positive cardiomyopathy. The receiver operating characteristic analysis indicated that posterior wall thickness (p < .0001, area under the curve [AUC]: .821, cut-off value: 14.0 mm), LVLSapi/bas (p < .001, AUC: .802, cut-off value: 2,16), and RVLS (p < .001, AUC: .791, cut-off value: -18.7%) could significantly detect 99m Tc-PYP positive results with an excellent credibility. Echocardiographic score points calculated using the summary of these three parameters in each patient revealed that a 2-point score had a fair sensitivity (85%) and an excellent specificity (93%), while a 1-point score had an excellent sensitivity (91%) and a modest specificity (53%). CONCLUSION: Our proposed echocardiographic screening tool for 99m Tc-PYP scintigraphy-positive cardiomyopathy may help clinicians manage patients with suspected ATTR-CM.

Right ventricular free wall longitudinal strain assessment using offline speckle tracking in COVID-19 patients requiring intensive medical care.

PURPOSE: The purpose of this study was to evaluate and confirm the prognostic utility of comprehensive transthoracic echocardiography (TTE) using offline myocardial strain analyses in a Japanese coronavirus disease (COVID-19) cohort hospitalized in intensive care units. METHODS: We performed a retrospective analysis of 90 consecutive adult patients with COVID-19 who underwent clinically indicated standard two-dimensional TTE in intensive care wards. Patients on extracorporeal membrane oxygenation (ECMO) at the time of TTE were excluded. Biventricular strain assessments using vendor-independent offline speckle tracking analysis were performed. Patients with inadequate TTE image quality were also excluded. RESULTS: Among the 90 COVID-19 patients, 15 (17%) patients required venovenous or venoarterial ECMO. There were 25 (28%) in-hospital deaths. A composite event, defined as the combination of in-hospital mortality and subsequent initiation of ECMO, occurred in 32 patients. Multivariate logistic regression for composite events indicated that right ventricular free wall longitudinal strain (RV-FWLS) and mechanical ventilation at the time of TTE were independent risk factors for composite events (p = 0.01, odds ratio [OR] 1.09, 95% confidence interval [CI] 1.01-1.18; p = 0.04, OR 3.24, 95% CI 1.03-10.20). Cumulative survival probability plots generated using the Kaplan-Meier method for composite events with log-rank tests revealed a significant difference between subgroups divided by the cutoff value of RV-FWLS (p < 0.001). CONCLUSION: Offline measurement of RV-FWLS may be a potent predictor of worse outcomes in COVID-19 requiring intensive care. Larger multicenter prospective studies are needed.

Interim Report of a Japanese Phase II Trial for Cardiac Stereotactic Body Radiotherapy in Refractory Ventricular Tachycardia　- Focus on Target Determination.

Background: Cardiac radiotherapy using stereotactic body radiation therapy (SBRT) has attracted attention as a minimally invasive treatment for refractory ventricular tachycardia. However, a standardized protocol and software program for determining the irradiation target have not been established. Here, we report the first preclinical stereotactic radioregulation antiarrhythmic therapy trial in Japan, focused on the target-setting process. Methods and Results: From 2019 onwards, 3 patients (age range 60-91 years) presenting with ischemic or non-ischemic cardiomyopathy were enrolled. Two patients were extremely serious and urgent, and were followed up for 6 and 30 months. To determine the irradiation targets, we aggregated electrophysiological, structural, and functional data and reflected them in an American Heart Association 17-segment model, as per the current recommendations. However, in all 3 patients, invasive electrophysiological study, phase-contrast computed tomography, and magnetic resonance imaging could not be performed; therefore, electrophysiological and structural information was limited. As alternatives, high-resolution ambulatory electrocardiography and nuclear medicine studies were useful in assessing arrhythmic substrates; however, concerns regarding test weighting and multiple scoring remain. Risks to surrounding organs were fully taken into account. Conclusions: In patients requiring cardiac SBRT, the information needed for target planning is sometimes limited to minimally invasive tests. Although there are issues to be resolved, this is a promising option for the life-saving treatment of patients in critical situations.

Utility and limitations of coherent mapping algorithm utilizing vectors and global propagation patterns in atrial tachycardia.

Background: A novel mapping algorithm utilizing vectors and global patterns of propagation (Coherent™, Biosense Webster) has been developed to help identify the mechanism of atrial tachycardia (AT). We aimed to determine the diagnostic accuracy of coherent mapping compared with that of ripple mapping. Methods and results: This study included 41 consecutive patients with 84 ATs (47 reentrant and 37 focal ATs). Two independent electrophysiologists confirmed the diagnoses using coherent mapping before the ripple map-guided ablation. AT termination was achieved in 75 of 84 ATs (89%) at first ablation lesion set. Four of the remaining nine ATs, which were terminated before an index radiofrequency (RF) application, were non-inducible after RF delivery at the first lesion set, whereas the other five ATs were terminated at the second lesion set. Diagnostic agreement between coherent and ripple maps was achieved in 51 of 84 ATs (61%): 28 of the 47 macroreentrant ATs (60%) and 23 of the 37 focal ATs (62%; P = 0.826). In typical macroreentrant ATs, including left atrial roof, perimitral, and cavotricuspid isthmus-dependent ATs, coherent maps achieved diagnostic agreement in 23 of 29 ATs (79%), which was higher than that in other ATs (51%, P = 0.018): 13 of 26 macroreentrant ATs (50%) and 15 of 29 focal ATs (52%, P = 1.000). Conclusion: Ripple map-guided AT ablation achieved a high termination rate in the first lesion set. Coherent mapping yielded a favorable diagnostic accuracy for typical macroreentrant ATs, though its value for diagnosing other ATs was limited.

Short-term Outcomes of Urgent Transcatheter Aortic Valve Replacement in Symptomatic Aortic Stenosis That Requires Emergency Hospital Admission.

Objective This study retrospectively compared the outcomes of emergently admitted patients with aortic stenosis (AS) with or without urgent transcatheter aortic valve replacement (TAVR). Methods Patients hospitalized between February 2015 and December 2019 for symptomatic AS were retrospectively analyzed by comparing the received conservative management [continued medical therapy with or without elective surgical transcatheter replacement (SAVR) or TAVR scheduled after the index hospitalization] and urgent TAVR (TAVR during the index hospitalization). Results The cohort comprised 114 patients with symptomatic AS who required emergency admission. Urgent TAVR was performed for 37 patients, while conservative management was provided for 77 patients, including 1 who received urgent SAVR. Urgent TAVR was more likely to be performed in patients with a history of hospitalization for heart failure, high New York Heart Association class scores, a lower clinical frailty scale at admission, and a high aortic valve peak velocity (p=0.01, p<0.001, p<0.01 and p=0.02, respectively). Kaplan-Meier analyses with log-rank test revealed favorable outcomes of urgent TAVR in all-cause mortality and cardiovascular events within 60 days of admission (p<0.01, p<0.01, respectively). Conclusion Urgent TAVR had better short-term outcomes in patients with symptomatic AS who required emergency hospital admission than conservative management. When considering urgent TAVR, patients with typical heart failure symptoms due to AS with a history of heart failure hospitalization and relatively little frailty can be selected.

Heavy Ion Irradiation Reduces Vulnerability to Atrial Tachyarrhythmias　- Gap Junction and Sympathetic Neural Remodeling.

BACKGROUND: Low-invasive stereotactic body radiation therapy is a novel anti-arrhythmic strategy. The mechanisms underlying its effects against ventricular tachycardia/fibrillation (VT/VF) are gradually becoming clear, whereas those underlying atrial tachycardia/fibrillation (AT/AF) remain unknown. This study investigated the effects of carbon ion beam on gap junction expression and sympathetic innervation.Methods and Results: Atrial and ventricular tachyarrhythmia models was established in 26 hypercholesterolemic (HC) 3-year-old New Zealand white rabbits; 12 rabbits were irradiated with a single 15-Gy carbon ion beam (targeted heavy ion irradiation [THIR]) and 14 were not (HC group). Eight 3-month-old rabbits (Young) were used as a reference group. In vivo induction frequencies in the Young, HC, and HC+THIR groups were 0%, 9.9%, and 1.2%, respectively, for AT/AF and 0%, 7.8%, and 1.2%, respectively, for VT/VF (P<0.01). The conduction velocity of the atria and ventricles on optical mapping was significantly reduced in the HC group; this was reversed in the HC+THIR group. Connexin-40 immunolabelling in the atria was 66.1-78.7% lower in the HC than Young group; this downregulation was less pronounced in the HC+THIR group (by 23.1-44.4%; P<0.01). Similar results were obtained for ventricular connexin-43. Sympathetic nerve densities in the atria and ventricles increased by 41.9-65.3% in the HC vs. Young group; this increase was reversed in the HC+THIR group. CONCLUSIONS: Heavy ion radiation reduced vulnerability to AT/AF and VT/VF in HC elderly rabbits and improved cardiac conductivity. The results suggest involvement of connexin-40/43 upregulation and suppression of sympathetic nerve sprouting.

Ablation index-guided cavotricuspid isthmus ablation with contiguous lesions using fluoroscopy integrated 3D mapping in atrial flutter.

PURPOSE: The feasibility and safety of cavotricuspid isthmus (CTI) ablation with contiguous lesions using ablation index (AI) under the guidance of fluoroscopy integrated 3D mapping (CARTO UNIVU/CU) in typical atrial flutter (AFL) remains uncertain. This study aimed to determine the efficacy of AI-guided CTI ablation with contiguous lesions in patients with AFL. METHODS: In this single-center, prospective, non-randomized, single-arm, observational study, procedural outcomes were determined in 151 patients undergoing AI-guided CTI ablation (AI group) with a target AI value of 450 and an interlesion distance of ≤ 4 mm under CU guidance. These outcomes were compared with those of 30 patients undergoing non-AI-guided ablation (non-AI group). RESULTS: Among 151 patients, first-pass conduction block was achieved in 120 (80%) patients in the AI group (67% in the non-AI group, P = 0.152) with a shorter fluoroscopy time of 0.2 ± 0.4 min (1.7 ± 2.0 min in the non-AI group, P < 0.001). Conduction gaps were located at the atrial aspects near the inferior vena cava in 24 of 31 (78%) patients without first-pass conduction block. The AI group received 11 ± 5 (12 ± 4 in the non-AI group, P = 0.098) radiofrequency (RF) applications, and the RF time was 4.2 ± 2.4 (5.1 ± 2.5 min in the non-AI group, P = 0.011). Despite the occurrence of steam pop in 3 (2%) patients, none of them developed cardiac tamponade. No patients had recurrence within 6 months of follow-up. CONCLUSIONS: AI-guided CTI ablation in combination with CU was feasible and effective in reducing radiation exposure in patients with AFL.

Ambulatory electrocardiographic markers predict serious cardiac events in patients with chronic kidney disease: The Japanese Noninvasive Electrocardiographic Risk Stratification of Sudden Cardiac Death in Chronic Kidney Disease (JANIES-CKD) study.

BACKGROUND: Noninvasive electrocardiographic markers (NIEMs) are promising arrhythmic risk stratification tools for assessing the risk of sudden cardiac death. However, little is known about their utility in patients with chronic kidney disease (CKD) and organic heart disease. This study aimed to determine whether NIEMs can predict cardiac events in patients with CKD and structural heart disease (CKD-SHD). METHODS: We prospectively analyzed 183 CKD-SHD patients (median age, 69 years [interquartile range, 61-77 years]) who underwent 24-h ambulatory electrocardiographic monitoring and assessed the worst values for ambulatory-based late potentials (w-LPs), heart rate turbulence, and nonsustained ventricular tachycardia (NSVT). The primary endpoint was the occurrence of documented lethal ventricular tachyarrhythmias (ventricular fibrillation or sustained ventricular tachycardia) or cardiac death. The secondary endpoint was admission for cardiovascular causes. RESULTS: Thirteen patients reached the primary endpoint during a follow-up period of 24 ± 11 months. Cox univariate regression analysis showed that existence of w-LPs (hazard ratio [HR] = 6.04, 95% confidence interval [CI]: 1.4-22.3, p = .007) and NSVT [HR = 8.72, 95% CI: 2.8-26.5: p < .001] was significantly associated with the primary endpoint. Kaplan-Meier analysis demonstrated that the combination of w-LPs and NSVT resulted in a lower event-free survival rate than did other NIEMs (p < .0001). No NIEM was useful in predicting the secondary endpoint, although the left ventricular mass index was correlated with the secondary endpoint. CONCLUSION: The combination of w-LPs and NSVT was a significant risk factor for lethal ventricular tachyarrhythmias and cardiac death in CKD-SHD patients.

Selexipag for the treatment of chronic thromboembolic pulmonary hypertension.

BACKGROUND: Treatment options for inoperable chronic thromboembolic pulmonary hypertension (CTEPH) remain limited. Selexipag, an oral selective IP prostacyclin receptor agonist approved for pulmonary arterial hypertension, is a potential treatment option for CTEPH. METHODS: In this multicentre, randomised, double-blind, placebo-controlled study, 78 Japanese patients with inoperable CTEPH or persistent/recurrent pulmonary hypertension after pulmonary endarterectomy and/or balloon pulmonary angioplasty were randomly assigned to receive placebo or selexipag. The primary end-point was the change in pulmonary vascular resistance (PVR) from baseline to week 20. Secondary end-points were changes in other haemodynamic parameters: 6-min walk distance (6MWD), Borg dyspnoea scale score, World Health Organization (WHO) functional class, EuroQol five-dimension five-level tool and N-terminal pro-brain natriuretic peptide. RESULTS: The change in PVR was -98.2±111.3 dyn·s·cm-5 and -4.6±163.6 dyn·s·cm-5 in the selexipag and placebo groups, respectively (mean difference -93.5 dyn·s·cm-5; 95% CI -156.8 to -30.3; p=0.006). The changes in cardiac index (p<0.001) and Borg dyspnoea scale score (p=0.036) were also significantly improved over placebo. 6MWD and WHO functional class were not significantly improved. The common adverse events in the selexipag group corresponded to those generally observed following administration of a prostacyclin analogue. CONCLUSION: Selexipag significantly improved PVR and other haemodynamic variables in patients with CTEPH, although exercise capacity remained unchanged. Further large-scale investigation is necessary to prove the role of selexipag in CTEPH.

Impact of exercise capacity on the long-term incidence of atrial arrhythmias in heart failure.

We sought to demonstrate the impact of improved peak exercise oxygen consumption (V̇O2) during maximal exercise testing after cardiac rehabilitation (CR) on the incidence of arrhythmias in patients with heart failure (HF). The present study comprised of 220 patients with HF, and peak V̇O2 was examined at 2 and 5 months after CR. Of the 220 patients, 110 (50%) had a low peak V̇O2 of < 14 mL/min/kg at 2 months. The peak V̇O2 improved in 86 of these 110 (78%) patients at 5 months after CR. During a median follow-up of 6 years, the patients with improvement in peak V̇O2, compared to those without peak V̇O2 improvement, had a lower rate of mortality (4% vs. 29%, log-rank, P < 0.001) and HF hospitalization (6 vs. 17%, log-rank, P = 0.044) and a lower incidence of new-onset atrial arrhythmias (9 vs. 27%, log-rank, P = 0.013), with no difference in the incidence of ventricular arrhythmias between groups (1 vs. 4%, log-rank, P = 0.309). The majority of deaths in the patients without an improved peak V̇O2 were because of cardiovascular events (73%), particularly progressive HF (55%). Early detection and management of atrial arrhythmias may improve outcomes in patients without peak V̇O2 improvement after CR.

Clinical Significance of the Head-Up Tilt Test in Improving Prognosis in Patients with Possible Neurally Mediated Syncope.

Syncope is commonly encountered in daily clinical practice. Depending on its etiology (benign or life-threatening conditions or environmental triggers), syncope can be neurally mediated (reflex), cardiac, or orthostatic. Furthermore, neurologic disease can cause symptoms that mimic syncope. However, there is limited research on neurally mediated syncope (NMS), which is considered a benign disorder, and close follow-ups are rarely performed. NMS can cause serious clinical events, including severe trauma and car accidents. The head-up tilt test (HUTT) is the gold standard for diagnosing NMS; however, its clinical significance remains unknown, and its relevance to NMS prognosis requires further research. This retrospective study aimed to assess the clinical significance of the HUTT for NMS. We reviewed the charts of 101 patients who underwent HUTT at Tokai University Hospital in Japan between January 2016 and March 2019. During the HUTT, 72 patients (69.2%) experienced syncope. Patients were followed up for 886.1 ± 457.7 days (interquartile range: 518-1293 days). The syncope recurrence rate was 16.9%; however, no significant difference was observed between the two groups (HUTT positive vs. negative) (13.8% vs. 18.1%, p = 0.772). Four of 29 (13.9%) and two of 72 (2.8%) patients in the negative and positive HUTT groups, respectively, experienced cardiac events (p = 0.019). Negative HUTT results may assist in anticipating unexpected clinical events within a few years. A negative HUTT result may allow us to reconsider the NMS diagnosis based on clinical information. Close outpatient follow-up of patients with negative HUTT results is warranted.