Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency: a systematic review.

Background: Immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency (IAD) is a rare but potentially fatal disease. Methods: We comprehensively searched the PubMed database and made a systematic review of immune checkpoint inhibitor-induced isolated adrenocorticotropic hormone deficiency. If the status of other anterior pituitary hormones was not mentioned, the case was excluded. Results: We identified 123 cases diagnosed as immune checkpoint inhibitor-induced IAD, consisting of 44 female and 79 male patients. The average age of these patients was 64.3 ± 12.6 years old, and 67.5% were 60 years old or above. The majority (78.9%) of these patients received anti-programmed cell death protein-1 (anti-PD-1) antibodies or anti-programmed cell death ligand 1 (anti-PD-L1) antibodies or both, and 19.5% received combined therapy, sequential therapy, or both. A total of 26 patients received anti-cytotoxic T lymphocyte antigen 4 antibodies (anti-CTLA-4). The median ICI treatment cycle before the diagnosis of adrenal insufficiency was 8 (6, 12), and the median ICI treatment duration before the diagnosis of adrenal insufficiency was 6 (4, 8) months. Eleven cases developed IAD 1 to 11 months after discontinuation of ICIs. Fatigue and appetite loss were the most common symptoms, and surprisingly, there were two asymptomatic cases of IAD. Most patients (88 cases) had normal pituitary magnetic resonance imaging, only 14 cases reported mild atrophy or swelling pituitary gland, and 21 cases reported no imaging results. Most diagnoses were made by basal hormone levels, and pituitary stimulation tests were performed in only a part of the cases. No cases had been reported of discontinuation of ICI use due to IAD nor had there been any deaths due to IAD. Conclusion: IAD was predominant in elderly male patients mainly receiving anti-PD-1 or anti-PD-L1 antibodies. It was sometimes difficult to recognize IAD at first glance since non-specific symptoms were common and asymptomatic cases of IAD were also reported. Although IAD can be deadly, it usually does not affect the continued use of ICIs.

Abnormal epicardial coronary vasomotor reactivity is associated with altered outcomes.

BACKGROUND: The prevalence and significance of abnormal epicardial coronary vasomotor reactivity (ACVR) in patients with symptoms compatible with myocardial ischaemia remains ill-defined. Our diagnostic strategy is to perform a provocative test (PT) in every patient presenting with chest pain at rest, for whom coronary angiography does not reveal significant epicardial coronary artery disease (≥70% stenosis by visual assessment). AIM: To evaluate such a strategy in terms of incidence of ACVR, PT safety and patient outcomes. METHODS: The present study was a retrospective observational study with a median clinical follow-up of 5years. The primary outcome was incidence of ACVR in patients with PT. Risk factors for ACVR and clinical follow-up were obtained, and the rate of major adverse cardiovascular and cerebrovascular events (MACCE; death, cardiovascular mortality, myocardial infarction, stroke and coronary revascularization) was reported. RESULTS: ACVR was documented in 294 (12.4%) of the 2379 patients with PT, out of the 13,654 patients undergoing angiography. Patients with ACVR were more often female (43.9% vs. 30.0%; P<0.0001), current smokers (37.4% vs. 8.7%; P<0.0001) and had a suspected acute coronary syndrome (36.7% vs. 29.1%; P=0.005) at admittance compared with patients without ACVR. During clinical follow-up, MACCE occurred more frequently in patients with (9.8%) than in those without (3.7%) ACVR (hazard ratio [HR] 4.15, 95% confidence interval [CI] 2.62-6.57; P<0.0001), including more myocardial infarctions (4.0% vs. 0.4%; HR 17.8, 95% CI 6.41-49.5; P<0.0001) and more myocardial revascularizations (6.1% vs. 1.1%; HR 9.36, 95% CI 4.67-18.74; P<0.0001) compared with patients with normal PT at baseline. CONCLUSIONS: ACVR is frequent in patients with symptoms compatible with myocardial ischaemia at rest, with no significant coronary stenosis. PT is a safe strategy to identify a population at high risk of recurrent ischaemic events.

Myocardial bridge evaluation towards personalized medicine: study design and preliminary results of the RIALTO registry.

Myocardial bridge (MB) is the most frequent inborn coronary artery variant in which a portion of the myocardium overlies an epicardial coronary artery segment. Although MB has long been considered a benign entity, a growing body of evidence has suggested its association with angina and adverse cardiac events. However, to date, no data on long-term prognosis are available, nor on therapies improving cardiovascular outcomes. We are currently conducting an ambispective, observational, multicentre, study in which we enrol patients with a clinical indication to undergo coronary angiography (CA) and evidence of MB, aiming to describe the incidence of symptoms and cardiovascular events at baseline and at long-term follow-up (FUP). The role of invasive full-physiology assessment in modifying the discharge therapy and eventually the perceived quality of life and the incidence of major cardiovascular events will be analysed. Basal clinical-instrumental data of eligible and consenting patients have been acquired after CA; FUP was performed 6, 12, and 24 months after the angiographic diagnosis of MB. The primary endpoint of the study is the incidence of major adverse cardiovascular events (MACE), defined as the composite of cardiac death, myocardial infarction, cardiac hospitalization, and target vessel revascularization; the secondary endpoints are the rate of patients with Seattle Angina Questionnaire (SAQ) summary score <70 and the incidence of MACE in patients undergoing invasive intracoronary assessment. Among patients undergone FUP visits, we recorded 31 MACE at 6 months (11.6%), 16 MACE at 12 months (6.5%), and 26 MACE at 24 months (13.5%). The rate of patients with SAQ <70 is 18.8% at 6 months, 20.6% at 12 months, and 21.8% at 24 months. To evaluate the prognostic role of invasive intracoronary assessment, we compared MB patients who underwent only angiographic evaluation (Angio group) to those who underwent acetylcholine (ACH) provocative test with indication to calcium-channel blockers (CCBs) at discharge (Angio + ACH + CCBs group) and those who underwent functional assessment with fractional flow reserve (FFR) with indication to beta-blockers (BBs) at discharge (Angio + FFR + BBs group). After 2 years of FUP, the rate of MACE was significantly reduced in both Angio + ACH + CCBs group (6 vs. 25%, P = 0.029) and Angio + FFR + BBs group (3 vs. 25%, P = 0.005) compared with Angio group. The preliminary results of our study showed that MB may be a cause of angina and adverse cardiac events in patients referred to CA for suspected coronary artery disease (CAD). Full-physiology assessment unmasking MB-related ischaemia mechanisms, allowed to guide the treatment, personalizing the clinical management, improving the quality of life, and cardiovascular outcomes in patients with MB.

Superselective Anesthesia Functional Examination of the Diaphragm during Endovascular Embolization of Spinal Cord Arteriovenous Malformation.

Superselective anesthesia functional evaluation (SAFE) is an adjunct to the Wada test. It is performed to rule out unintentional positioning of the tip of the embolization catheter proximal to the origin of a normal artery supplying eloquent region of spinal cord. We report a case of a 36-year-old male with cervical intramedullary spinal cord arteriovenous malformation (SCAVM) at C3 level. In this patient, we monitored motor-evoked potentials (MEPs) of bilateral upper and lower limbs along with diaphragm. Electrodes for compound muscle action potential of diaphragm were placed under fluoroscopy guidance. Through this case, we want to emphasize that intraprocedural diaphragmatic MEPs enhance the safety margin during endovascular embolization of cervical intramedullary SCAVMs. Placement of electrodes under fluoroscopy guidance ensures proper positioning into the diaphragm muscle.

Development of early diagnosis of Parkinson's disease on animal models based on the intranasal administration of α-methyl-p-tyrosine methyl ester in a gel system.

The fight against neurodegenerative diseases, including Parkinson's disease (PD), is a global challenge of this century. The effectiveness of current PD therapy is limited, since it is diagnosed many years after the onset, following the death of most nigrostriatal dopaminergic neurons regulating motor function. PD treatment could be greatly improved if it was started at an early (preclinical) stage. For this purpose, it is necessary to develop an early diagnosis of PD, which is the goal of our study. We have developed an early diagnosis of PD on animal models using a provocative test by intranasal administration of α-methyl-p-tyrosine methyl ester (αMPTME), a reversible inhibitor of dopamine synthesis. First, we produced the provocative agent, αMPTME in gel, and showed its safety and penetration into the brain bypassing the blood-brain barrier. Then, the optimal dose of αMPTME and time after administration were selected, at which the level of dopamine in the striatum of intact animals decreases, but does not reach the 30% threshold for the appearance of motor disorders in PD patients. Finally, we proved on animal models that intranasal administration of αMPTME can serve as a diagnostic test for preclinical PD. Indeed, intranasal administration of αMPTME to mice in a model of PD at the preclinical stage reversibly reduced the dopamine level in the striatum to the 30% threshold causing short-term motor disorders. Thus, using animal models of PD, we have developed a provocative test for the preclinical diagnosis of PD, a fundamentally new technology in neurology.

Endovascular treatment of an infectious aneurysm using the selective provocative test and transcranial motor evoked potential monitoring under general anesthesia: a case report.

The selective provocative test (SPT) under local anesthesia aids in protecting against ischemic complications during endovascular treatment. However, the use of this test under general anesthesia is not well described. Herein, we present a case of a 51-year-old man with a ruptured fusiform aneurysm in the middle cerebral artery M4 segment, which was thought to possibly supply the motor cortex. Internal trapping of the affected vessel and aneurysm by endovascular intervention was successfully performed after SPT using transcranial motor evoked potential (MEP) monitoring under general anesthesia. Transcranial MEP is suitable for neurological assessment during SPT under general anesthesia.

Macimorelin Acetate for the Diagnosis of Childhood-onset Growth Hormone Deficiency.

Growth hormone provocation testing forms the cornerstone of the diagnosis of childhood growth hormone deficiency in clinical practice. Despite the widespread use of these tests, various criticisms have been levelled against them, such as the labour-intensive nature of the tests, their potential for serious adverse effects and their questionable reproducibility. Macimorelin acetate, a ghrelin mimetic approved for the diagnosis of adult growth hormone deficiency, could serve an unmet need in the diagnosis of childhood-onset growth hormone deficiency based on its good tolerability and benign side effect profile.

Diagnostic Value of Frequently Implemented Provocative Tests in the Assessment of Shoulder Pain-A Glimpse of Current Practice.

Initial evaluation of chronic shoulder disability is a diagnostic challenge due to the anatomic complexity of the shoulder joints. For this purpose, several diagnostic tools utilizing provocative testing exist, but only a few have a reliable basis for their diagnostic value. Therefore, objectively determining the predictive value of these tests in identifying the precise anatomical source for disability-subacromial, intraarticular or other-is essential in order to proceed with further imaging evaluations for final objective diagnoses. Using validated clusters of provocative tests should improve their diagnostic values.

Coronary provocative tests in the catheterization laboratory: Pathophysiological bases, methodological considerations and clinical implications.

The paradigm for the management of patients presenting with angina and/or myocardial ischemia has been historically centered on the detection and treatment of obstructive coronary artery disease (CAD). However, in a considerable proportion (30-50%) of patients undergoing coronary angiography, obstructive CAD is excluded. Thus, functional mechanisms may be involved in determining myocardial ischemia and should be investigated. In particular, coronary vasomotor disorders both at epicardial and at microvascular level may play a crucial role, but a definitive diagnosis of these disorders can at times be difficult, given the transience of symptoms, and often requires the use of coronary provocative tests. Of importance, these tests may provide relevant information on the pathogenic mechanism of myocardial ischemia, allowing physicians to tailor the therapies of their patients. Furthermore, several studies underscored the important prognostic information deriving from the use of coronary provocative tests. Nevertheless, their use in clinical practice is currently limited and mainly restricted to specialized centers, with only a minority of patients receiving a benefit from this diagnostic approach. In this review, we explain the pathophysiological bases for the use of provocative tests, along with their clinical, prognostic and therapeutic implications.

Clinical, angiographic and echocardiographic correlates of epicardial and microvascular spasm in patients with myocardial ischaemia and non-obstructive coronary arteries.

BACKGROUND: Coronary vasomotor dysfunction represents an important mechanism responsible for myocardial ischaemia in patients with non-obstructive coronary artery disease (CAD). The use of invasive provocative tests allows identifying patients with epicardial or microvascular spasm. Of note, clinical characteristics associated with the occurrence of epicardial or microvascular spasm have still not completely clarified. METHODS AND RESULTS: We prospectively enrolled consecutive patients undergoing coronary angiography for suspected myocardial ischaemia/necrosis with evidence of non-obstructive CAD and undergoing intracoronary provocative test for suspected vasomotor dysfunction. Patients with a positive provocative test were enrolled. Clinical, echocardiographic and angiographic characteristics of patients were evaluated according to the pattern of vasomotor dysfunction (epicardial vs. microvascular spasm). We included 120 patients [68 patients with stable angina and 52 patients with myocardial infarction and non-obstructive coronary arteries (MINOCA)]. In particular, 77 (64.2%) patients had a provocative test positive for epicardial spasm and 43 (35.8%) patients for microvascular spasm. Patients with epicardial spasm were more frequently males, smokers, had higher rates of diffuse coronary atherosclerosis at angiography and more frequently presented with MINOCA. On the other hand, patients with microvascular spasm presented more frequently diastolic dysfunction. At multivariate logistic regression analysis male sex, smoking, and diffuse coronary atherosclerosis were independent predictors for the occurrence of epicardial spasm. CONCLUSIONS: Our study showed that specific clinical features are associated with different responses to intracoronary provocative test. Epicardial spasm is more frequent in males and in MINOCA patients, whereas microvascular spasm is more frequent in patients with stable angina and is associated with diastolic dysfunction.

The value of prednisolone acetate provocative test before intravitreal triamcinolone acetonide injections.

PURPOSE: The aim of this study was to investigate the diagnostic value of a topical prednisolone acetate 1% provocative test for steroid-induced ocular hypertension before intravitreal triamcinolone acetonide injection. METHODS: This is a prospective, single-center, randomized controlled study at Kasr El Aini Hospital, Cairo University. Patients scheduled for intravitreal triamcinolone acetonide were enrolled and randomly allocated in a ratio 2:1 to either Group A: received prednisolone acetate provocative test and those who did not develop SIOH proceeded with intravitreal triamcinolone acetonide or Group B: did not receive prednisolone acetate provocative test and proceeded directly to intravitreal triamcinolone acetonide. Intraocular pressures were measured weekly for 4 weeks following intravitreal triamcinolone acetonide. Steroid-induced ocular hypertension is defined as intraocular pressure increase of 5 mmHg or more from baseline after prednisolone acetate provocative test or intravitreal triamcinolone acetonide. RESULTS: A total of 66 eyes (66 patients) were included. Of which, 10 eyes (23.8%) showed prednisolone acetate provocative test steroid-induced ocular hypertension during the 4-week period. Intravitreal triamcinolone acetonide steroid-induced ocular hypertension was less likely to develop in Group A (prednisolone acetate provocative test non-steroid-induced ocular hypertension, n = 32, 31.25%) than in group B (n = 24, 54.2%) (p = 0.006, odds ratio: 0.178, 95% CI: 0.53-0.596). Our test achieved a negative predictive value of 68.75%. CONCLUSION: The topical prednisolone acetate provocative test may be a useful method to predict a steroid-induced ocular hypertension following intravitreal triamcinolone acetonide.

[Vasospastic angina: An under-diagnosed pathology]. / L'angor spastique : une pathologie sous-diagnostiquée.

The clinical and physiopathological clinical entity known as spastic angina or variant angina has been long documented. It remains, however, an under-estimated condition, which is insufficiently diagnosed and explored. This pathology is associated with severe complications such as heart rhythm disorders, which may potentially result in ventricular fibrillation and cause sudden death. In Japan, this condition occurs more frequently and is better documented. Stimulation tests are also carried out more often and have a higher positivity rate than in France where vasospastic angina is less frequently reported and where provocation tests are associated with negative results and are, consequently, performed less often. In order to improve the detection of this pathology, its potential presence should be explored in patients with rest angina who experience chest pain in the second half of the night and also in instances of acute coronary syndrome with sudden death and no angiographically visible coronary artery disease. The diagnosis should be confirmed by means of ergonovine provocation tests. In order to enhance the sensitivity of these tests without increasing the risk of complications, injection of ergonovine should be preferably carried out via the intracoronary route. By increasing the frequency and sensitivity of these tests, this pathology, which responds well to medical treatment in many cases, could be amenable to therapeutic management as any other form of coronary artery disease.

Iris lens distance to predict the risk of intraocular pressure elevation after dark room provocative test.

PURPOSE: To investigate if a new ultrasound biomicroscopy (UBM) parameter, iris lens distance (ILD), and its model could predict clinically significant intraocular pressure (IOP) elevation after darkroom provocative test (DRPT). METHODS: Cases with a peripheral anterior chamber depth less than one-fourth corneal thickness were enrolled. All subjects underwent UBM examination and DRPT if possible. Anterior chamber depth (ACD) and ILD were measured in the central axis at different positions in dark (ACDD, ILDD) and bright (ACDB, ILDB). An IOP elevation over 5 mmHg and 8 mmHg was set as cutoffs for a positive DRPT result (positive-5 and positive-8). SAS 9.3 statistical software was used to manage and analyze data and calculate the linear probability model (LPM). Another 17 patients (34 eyes) were included to validate the model. RESULTS: Two hundred and ten (210) UBM images qualified for analysis. ILD was significantly less in the dark than in the bright and in patients with a positive DRPT result (p < 0.001). The LPM for positive-5 and positive-8 were P = 1.14 + (- 0.49*ILDD) + (- 0.41*ACDD) (n = 210, R2 = 0.1079, AUC = 0.715), and P = 0.87 + (- 0.44*ILDD) + (- 0.35*ACDD) (n = 210, R2 = 0.1358, AUC = 0.807), respectively. CONCLUSIONS: LPMs based on ILD could predict the risk of an IOP elevation over 5 mmHg or 8 mmHg. The LPM for positive-8 reached a good level of diagnostic accuracy.

Peak Growth Hormone Response to Combined Stimulation Test in 315 Children and Correlations with Metabolic Parameters.

BACKGROUND/AIMS: Studies are lacking regarding the timing of peak growth hormone (PGH) response. We aim to elucidate the timing of PGH response to arginine and levodopa (A-LD) and evaluate the influence of body mass index (BMI) and other metabolic parameters on PGH. METHODS: During growth hormone (GH) stimulation testing (ST) with A-LD, serum GH was measured at baseline and every 30 min up to 180 min. The PGH cut-off was defined as &#x3c;10 ng/mL. IGF-1, IGF BP3, BMI, and metabolic parameters were obtained in a fasting state at baseline. RESULTS: In the 315 tested children, stimulated PGH levels occurred at or before 120 min in 97.8% and at 180 min in 2.2%. GH area under the curve (AUC) positively correlated with PGH in all patients and with IGF-1 in pubertal males and females. BMI negatively correlated with PGH in all subjects. GH AUC negatively correlated with HOMA-IR and total cholesterol. CONCLUSION: We propose termination of the GH ST with A-LD at 120 min since omission of GH measurement at 180 min did not alter the diagnosis of GH deficiency based on a cut-off of &#x3c; 10 ng/mL. BMI should be considered in the interpretation of GH ST with A-LD. The relationships between GH AUC and metabolic parameters need further study.

Significance of Provocative Perfusion Computed Tomography for Evaluation of Bow Hunter Syndrome.

Bow hunter syndrome (BHS) is a rare vascular phenomenon of vertebrobasilar insufficiency caused by dynamic stenosis of the vertebral artery (VA) by osteophytes, fibrous bands, or disk herniation with neck rotation. We present a rare case of a patient with bilaterally patent VAs on neutral imaging and bilateral dynamic compression of VA with left head rotation. Provocation tests are critical toward understanding dynamic pathophysiology of BHS because normal neutral vascular imaging does not preclude diagnosis of BHS. Although dynamic angiography is the gold standard for diagnosis of BHS, cerebral angiography could be invasive and risky. Provocative test using perfusion computed tomography scan is a simple and noninvasive method to assess BHS on an outpatient basis.

Growth hormone provocative test of 5 036 cases in pediatric clinic: a single center nursing / 中国实用护理杂志

Objective@#To explore the nursing experience of growth hormone provocative test in pediatric clinic.@*Methods@#Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat-sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test.@*Results@#All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58%) had different degrees of adverse reactions including nausea, vomiting, abdominal pain, sweating, salivation, dizziness, pallor, etc., most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms.@*Conclusion@#Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

Growth hormone provocative test of 5 036 cases in pediatric clinic: a single center nursing / 中国实用护理杂志

Objective To explore the nursing experience of growth hormone provocative test in pediatric clinic. Methods Five thousand and thirty-six children with short stature or slowing growth received combined simultaneous Levodopa Pyridostigmine stimulation test from June 2008 to October 2018 in the Child Growth Center of the First Affiliated Hospital of SUN Yat- sen University. Comprehensive nursing intervention was conducted to ensure the test carry through successfully before, during and after the test. Results All children completed the five collections in the 120-minute growth hormone provocative test without cannula obstruction and blurt out. Some (986 out of 5 036 children, 19.58% ) had different degrees of adverse reactions including nausea,vomiting,abdominal pain, sweating,salivation,dizziness,pallor,etc.,most of which disappeared or alleviated after nursing, except 11 patients (0.22%) needed atropine muscular injection and 3 of whom needed intravenous fluids to release the marked symptoms. Conclusion Combined simultaneous Levodopa Pyridostigmine stimulation test is safe and practicable in pediatric clinics with nursing experience.

Combined simultaneous arginine clonidine stimulation test: Timing of peak growth hormone (GH) concentration and correlation with clinical indices of GH status.

BACKGROUND: The aims of this study were to determine if it is possible to truncate a combined simultaneous arginine clonidine stimulation test, and to correlate the outcome of the test with clinical indices of GH status. METHODS: Charts of subjects who underwent a combined simultaneous arginine clonidine stimulation test between January 1, 2007 and August 31, 2016 were reviewed. RESULTS: 131/203 (64.5%) tests performed in children with growth failure demonstrated a peak GH ≥ 10 ng/ml. 6/7 (85.7%) tests performed in adolescents at the end of GH treatment had a peak GH ≥ 5 ng/ml. Among these negative tests, 97.8% had a passing GH by 120 min. 58/98 (59.1%) tests that had a sample at 150 min were negative. 3/58 (5.2%) had a passing GH level only at 150 min. Therefore, if the test were shortened to 120 min, 5.2% of normal responders would be missed. There was a weak correlation of peak GH with baseline growth velocity and serum IGF-1 z-score. A trend towards an inverse correlation between peak GH level and change in growth velocity pre- and post-GH was seen. CONCLUSIONS: If the combined simultaneous arginine clonidine test were shortened to 120 min, 5.2% of normal responders would be missed. Although this test has not been compared to any "gold standard" GH stimulation test, the outcome of this test does correlate weakly with clinical indices of GH status and spares patients the inconvenience of sequential testing.

Patients with acute myocardial infarction and non-obstructive coronary arteries: safety and prognostic relevance of invasive coronary provocative tests.

Aims: Functional alterations of epicardial coronary arteries or coronary microcirculation represent a frequent cause of myocardial infarction and non-obstructive coronary arteries (MINOCA). We aimed at assessing the prognostic value of intracoronary provocative tests in patients presenting with MINOCA and in which other causes of MINOCA have been excluded. Methods and results: We prospectively evaluated patients with a diagnosis of MINOCA, excluding patients with aetiologies other than suspected coronary vasomotor abnormalities. Immediately after coronary angiography, an invasive provocative test using acetylcholine or ergonovine was performed. The incidence of death from any cause, cardiac death, and recurrence of acute coronary syndrome (ACS) was assessed at follow-up. We also assessed angina status using Seattle Angina Questionnaires (SAQ). We enrolled 80 consecutive patients [mean age 63.0 ± 10.7 years, 40 (50%) male]. Provocative test was positive in 37 (46.2%) patients without any complication. Among patients with a positive test, epicardial spasm was detected in 24 (64.9%) patients and microvascular spasm in 13 (35.1%) patients. After a median follow-up of 36.0 (range 12.0-60.0) months, patients with a positive test had a significantly higher occurrence of death from any cause [12 (32.4%) vs. 2 (4.7%); P = 0.002], cardiac death [7 (18.9%) vs. 0 (0.0%); P = 0.005], and readmission for ACS [10 (27.0%) vs. 3 (7.0%); P = 0.015] as well as a worse angina status as assessed by SAQ [Seattle score: 88.0 (33.0-100.0) vs. 100.0 (44.0-100.0); P = 0.001] when compared with patients with a negative test. Conclusions: We demonstrate that in patients presenting with MINOCA and suspected coronary vasomotor abnormalities, a positive provocative test for spasm is safe and identifies a high-risk subset of patients.