Administration Of Nitroglycerin Research Articles

VERMONT non-optimised: can baseline diagnostic catheter images be used to measure angiography based CAAS-vFFR?

Abstract Background We have previously reported strong diagnostic accuracy and validity of angiography-based vessel Fractional Flow Reserve (CAAS-vFFR) compared to conventional wire based Fractional Flow Reserve (FFR)(1). The CAAS-vFFR system requires at least two additional optimised angiographic cine images taken after intracoronary glyceryl trinitrate administration, separated by ≥ 30 degrees at a frame-rate of ≥ 15 frames/seconds with minimal overlap and foreshortening, no table movement and adequate contrast opacification. At present, there is a paucity of data regarding the validity of using baseline non-optimised diagnostic cine images in the assessment of CAAS-vFFR. Purpose To assess the concordance and validity of using baseline non-optimised diagnostic cine images in measuring angiography based CAAS-vFFR. Methods We conducted an investigator-initiated, single centre, blinded, prospective observational study performing wire based FFR and CAAS-vFFR conducted simultaneously in patients undergoing routine wire-based FFR for intermediate coronary stenoses. All eligible patients had baseline diagnostic and optimised guide-catheter based angiographic images acquired. Results 195 consecutive patients with 205 lesions were recruited over 19 months; 56 (27.3%) lesions were excluded due to inadequate baseline cine angiogram images (Picture 1). 102 (68.5%) had stable symptoms and 107 (71.8%) were male. The median age was 65.0 years (interquartile range 59.0 – 73.0) and mean body-mass-index was 29.2 kg/m2 (± 5.8). There were 117 (78.5%) lesions in the left anterior descending artery/diagonal branches, 20 (13.4%) in the right coronary artery and 12 (8.1%) in the left circumflex artery/marginal branches. There were 93 (62.4%) diffuse (≥ 20 cm), 23 (15.4%) bifurcation and 15 (10.1%) ostial lesions. The mean optimised vFFR and non-optimised vFFR were 0.80 (± 0.1) and 0.79 (± 0.1) respectively with a Pearson correlation of 0.87 (p<0.001). Overall, 52 lesions (34.9%) and 73 lesions (49.0%) had a wire-based FFR and non-optimised vFFR value of ≤ 80 respectively. The mean wire-based FFR and non-optimised vFFR were 0.82 (± 0.1) and 0.79 (± 0.1) respectively. Receiver operating characteristic (ROC) curve analysis revealed excellent diagnostic accuracy of non-optimised vFFR in predicting a wire based FFR of ≤ 80 (AUC 0.91; 95% CI; 0.87-0.96) (Picture 2). Baseline non-optimised diagnostic vFFR images produced a sensitivity of 94.2%, specificity of 75.3%, positive-predictive-value (PPV) of 67.1% and negative-predictive-value (NPV) of 96.1% compared with wire-based FFR. Conclusions CAAS-vFFR derived values from baseline non-optimised diagnostic cine images were strongly concordant with those derived from optimised images and displayed a high sensitivity and NPV compared to wire-based FFR. This reflects the potential for CAAS-vFFR to have broader clinical applications and be utilised as a retrospective screening tool for intermediate lesions.Excluded baseline angiogram lesionsROC Curve

1H-MRS reveals abnormal energy metabolism and excitatory-inhibitory imbalance in a chronic migraine-like state induced by nitroglycerin in mice

BackgroundChronic migraine is closely related to the dysregulation of neurochemical substances in the brain, with metabolic imbalance being one of the proposed causes of chronic migraine. This study aims to evaluate the metabolic changes between energy metabolism and excitatory and inhibitory neurotransmitters in key brain regions of mice with chronic migraine-like state and to uncover the dysfunctional pathways of migraine.MethodsA chronic migraine-like state mouse model was established by repeated administration of nitroglycerin (NTG). We used von Frey filaments to assess the mechanical thresholds of the hind paw and periorbital in wild-type and familial hemiplegic migraine type 2 mice. After the experiments, tissue was collected from five brain regions: the somatosensory cortex (SSP), hippocampus, thalamus (TH), hypothalamus, and the spinal trigeminal nucleus caudalis (TNC). Proton magnetic resonance spectroscopy (1H-MRS) was employed to study the changes in brain metabolites associated with migraine, aiming to explore the mechanisms underlying metabolic imbalance in chronic migraine-like state.ResultsIn NTG-induced chronic migraine-like state model, we observed a significant reduction in energy metabolism during central sensitization, an increase in excitatory neurotransmitters such as glutamate, and a tendency for inhibitory neurotransmitters like GABA to decrease. The TNC and thalamus were the most affected regions. Furthermore, the consistency of N-acetylaspartate levels highlighted the importance of the TNC-TH-SSP pathway in the ascending nociceptive transmission of migraine.ConclusionAbnormal energy metabolism and neurotransmitter imbalance in the brain region of NTG-induced chronic migraine-like state model are crucial mechanisms contributing to the chronicity of migraine.

Acute coronary syndrome due to coronary vasospasm: a case report.

Coronary vasospasm can lead to decreased cardiac perfusion and result in acute coronary syndrome. Here is a case of a 49-year-old man presented to the emergency department with epigastric pain and nausea with normal initial electrocardiogram. However, 6h later, the patient experienced severe chest pain prompting a repeat electrocardiogram demonstrating inferior ST-segment elevation with troponin I levels peaked at 1.2ng/ml (normal range: 0.00-0.02ng/ml). Coronary angiography revealed angiographic stenosis in the left circumflex territory of a left dominant system which resolved with intracoronary nitroglycerin administration indicating ischemia with nonobstructive coronary arteries secondary to coronary vasospasm. He was discharged on isosorbide mononitrate and amlodipine therapy and had no recurrence of symptoms during follow-up.

Type I Kounis syndrome in a young woman without chest pain: a case report

BackgroundKounis syndrome is defined as the concurrence of acute coronary syndromes in the setting of allergic or anaphylactic reactions. It primarily affects men aged 40–70 years and is often associated with chest pain. This syndrome is often unrecognized and undiagnosed in clinical practice due to a low level of awareness. Herein, we present a case of type I Kounis syndrome in a young woman without chest pain.Case presentationA 28-year-old Japanese woman with a history of atopic dermatitis received a glycyrrhizin, glutathione, and neurotropin preparation (a preparation of inflamed skin extract from rabbits inoculated with vaccinia virus) at a dermatology clinic to treat pruritus caused by atopic dermatitis. Immediately after the administration, the patient developed abdominal pain and generalized body wheals. The patient was diagnosed with anaphylaxis and was transported to our hospital. She had no chest pain on arrival at our hospital; however, a 12-lead electrocardiogram showed ST elevation in leads I, aVL, V2, and V3, and an echocardiogram showed decreased wall motion in the anterior and lateral walls of the left ventricle. Sublingual nitroglycerin administration improved ST-segment elevation and left ventricular wall motion abnormalities. The patient underwent emergency coronary angiography, which revealed no significant stenosis, and was diagnosed with type I Kounis syndrome.ConclusionKounis syndrome without chest pain is rare in young women. Since it can be fatal in cases with severe allergic symptoms such as anaphylaxis, the possibility of concurrent acute coronary syndrome should be considered when treating systemic allergic reactions, regardless of age, sex, or the presence or absence of chest symptoms.

Effects of Co-administration of Fentanyl and Nitroglycerin on Hemodynamic Responses During Intubation and Extubation: A Randomized Clinical Trial

PurposeThis study was conducted with the aim of investigating the effects of simultaneous administration of fentanyl and nitroglycerine on hemodynamic responses. DesignThis randomized controlled trial was conducted with 50 patients undergoing elective inguinal hernia surgery. MethodsPatients were randomly divided into two groups. In one group, fentanyl (F) was administered 5 minutes before intubation and extubation. In the other group, in addition to F, sublingual nitroglycerine spray was administered 2 minutes before intubation and extubation. Systolic, diastolic, and mean blood pressure and heart rate were measured before, immediately after, and at 1, 3, and 5 minutes after both procedures. FindingsSystolic, diastolic, and mean blood pressure and heart rate were significantly lower in the group receiving fentanyl and nitroglycerine than in the group receiving fentanyl alone. In both groups, a reduction in hemodynamic variables was observed immediately after both procedures, up to 5 minutes later, but it was significantly reduced in the group receiving simultaneous administration of the two drugs. ConclusionsCo-administration of nitroglycerine and fentanyl significantly weakened the hemodynamic responses and reflexes induced by intubation and extubation during the anesthesia process. Preventing these unwanted complications can lead to safer anesthesia for susceptible patients.

Radial Artery Spasm-A Review on Incidence, Prevention and Treatment.

Radial artery spasm (RAS) is a common complication associated with transradial access (TRA) for coronary interventions, particularly affecting elderly patients in whom radial access is preferred due to its benefits in reducing bleeding complications, improving clinical outcomes, and lowering long-term costs. This review examines the incidence, prevention, and treatment of RAS. Methods included an online search of PubMed and other databases in early 2024, analyzing meta-analyses, reviews, studies, and case reports. RAS is characterized by a sudden narrowing of the radial artery due to psychological and mechanical factors with incidence reports varying up to 51.3%. Key risk factors include patient characteristics like female sex, age, and small body size as well as procedural factors such as emergency procedures and the use of multiple catheters. Preventive measures include using distal radial access, hydrophilic sheaths, and appropriate catheter sizes. Treatments involve the intraarterial administration of nitroglycerine and verapamil as well as mechanical methods like balloon-assisted tracking. This review underscores the need for standardizing RAS definitions and emphasizes the importance of operator experience and patient management in reducing RAS incidence and improving procedural success.

Computed tomography angiography assessment of Adamkiewicz artery with sublingual nitroglycerin administration.

Identification of the Adamkiewicz artery before aortic surgery is important for preventing postoperative complications due to spinal cord ischemia. The Adamkiewicz artery is difficult to identify due to its small diameter. Nitroglycerin has a vasodilatory effect and is used clinically to improve visualization of blood vessels on coronary computed tomography (CT) angiography. We investigated whether the vasodilatory effect of nitroglycerin could improve the ability to visualize the Adamkiewicz artery. We extracted 33 cases wherein contrast-enhanced CT images were taken before and after aortic aneurysm surgery. Nitroglycerin was administered for coronary artery evaluation on the preoperative CT. However, no nitroglycerin was administered before the postoperative CT. Aortic contrast-to-noise ratio, CT value, image noise, and diameter of the Adamkiewicz artery and anterior spinal artery were measured. The depiction of the Adamkiewicz artery was graded into four grades and evaluated. These measurements were performed by two independent reviewers. In nitroglycerin-administered cases, the contrast-to-noise ratio and CT values were significantly higher (P < 0.001, P < 0.001, respectively); the Adamkiewicz artery and anterior spinal artery diameters were dilated (P = 0.005, P = 0.001, respectively). The Adamkiewicz artery score also improved significantly (P < 0.001). No significant difference was found in image noise. Nitroglycerin contributed to improving the Adamkiewicz artery's visualization.

Nitroglycerin combined with NSAIDs for prevention of post-ERCP pancreatitis: A meta-analysis of prospective, randomized, controlled trials.

Acute pancreatitis is the most common complication of endoscopic retrograde cholangiopancreatography (ERCP), with an incidence of approximately 9.7% according to some literature reviews. Recent clinical guidelines propose that glyceryl trinitrate (GTN) can reduce the incidence of post-ERCP pancreatitis (PEP). However, currently, no guidelines provide an exact opinion on GTN and nonsteroidal anti-inflammatory drugs (NSAIDs) to prevent post-ERCP pancreatitis. A meta-analysis was performed of published, full-length, randomized controlled trials (RCTs) evaluating the effects of prophylactic use of GTN, including GTN alone or GTN in combination with NSAIDs, on the prevention of PEP. Literature searches were conducted using PubMed, Embase, Web of Science, and The Cochrane Library. Search terms included "endoscopic retrograde cholangiopancreatography" OR "ERCP," "OR 'PEP' OR 'post-endoscopic retrograde cholangiopancreatography pancreatitis', pancreatitis," "GTN" OR "glyceryl trinitrate" OR "nitroglycerin," "NSAIDs" OR "Nonsteroidal Anti-inflammatory Drugs" and limited to RCT. A total of 10 RCTs comprising 3240 patients undergoing ERCP were included. Meta-analysis revealed that the administration of GTN was associated with a significant reduction in the overall incidence of PEP. Moreover, PEP incidence was significantly lower in the GTN combined with the NSAIDs group than in the GTN alone group. GTN alone or GTN combined with NSAIDs may not reduce the severity of PEP (risk ratio = 0.64; 95% confidence interval: 0.41-0.99; P = .04). The difference in incidence between the 2 groups is 1.01% (6/594) in the GTN with NSAIDs group and 2.36% (14/592) in the placebo group. GTN has a significant benefit in preventing postoperative ERCP pancreatitis (P < .001). And neither GTN nor GTN plus NSAIDs reduces the incidence of non-mild ERCP postoperative pancreatitis. These conclusions need to be confirmed by high-quality randomized controlled studies with multicenter, large samples, and long-term follow-up.

Noninvasive assessment of human microvascular function in health and disease using incident dark-field microscopy.

Reduced peripheral microvascular reactivity is associated with an increased risk for major adverse cardiac events (MACEs). Tools for noninvasive assessment of peripheral microvascular function are limited, and existing technology is poorly validated in both healthy populations and patients with cardiovascular disease (CVD). Here, we used a handheld incident dark-field imaging tool (CytoCam) to test the hypothesis that, compared with healthy individuals (no risk factors for CVD), subjects formally diagnosed with coronary artery disease (CAD) or those with ≥2 risk factors for CAD (at risk) would exhibit impaired peripheral microvascular reactivity. A total of 17 participants (11 healthy, 6 at risk) were included in this pilot study. CytoCam was used to measure sublingual microvascular total vessel density (TVD), perfused vessel density (PVD), and microvascular flow index (MFI) in response to the topical application of acetylcholine (ACh) and sublingual administration of nitroglycerin (NTG). Baseline MFI and PVD were significantly reduced in the at-risk cohort compared with healthy individuals. Surprisingly, following the application of acetylcholine and nitroglycerin, both groups showed a significant improvement in all three microvascular perfusion parameters. These results suggest that, despite baseline reductions in both microvascular density and perfusion, human in vivo peripheral microvascular reactivity to both endothelial-dependent and -independent vasoactive agents remains intact in individuals with CAD or multiple risk factors for disease.NEW & NOTEWORTHY To our knowledge, this is the first study to comprehensively characterize in vivo sublingual microvascular structure and function (endothelium-dependent and -independent) in healthy patients and those with CVD. Importantly, we used an easy-to-use handheld device that can be easily translated to clinical settings. Our results indicate that baseline microvascular impairments in structure and function can be detected using the CytoCam technology, although reactivity to acetylcholine may be maintained even during disease in the peripheral microcirculation.

Type 1 Kounis syndrome: recurrent myocardial infarctions in a patient with aspirin-exacerbated respiratory disease: a case report

Introduction. We present a case of type 1 Kounis syndrome in a patient with recurrent myocardial infarction with non-obstructive coronary arteries (MINOCA) due to allergic coronary vasospasm. Awareness of doctors about this pathology will allow identifying the MINOCA causes and prescribing pathogenetic treatment.Brief description. A 51-year-old woman with aspirin-exacerbated respiratory disease (asthma, rhinosinusitis with nasal polyposis, aspirin hypersensitivity, eosinophilia) without cardiovascular risk factors developed three recurrent myocardial infarctions against the background of vasospastic angina over a 6-month period. Despite the typical clinical performance, stable ST segment elevation, unchanged coronary arteries on coronary angiography, the vasospastic MI was not immediately established. The patient received long-term treatment for type 1 MI, including beta-blockers. Recurrent MI occurred against the background of an asthma attack. During the second and third hospitalization for MI, coronary angiography revealed a spasm of the right coronary artery, which completely resolved with the nitroglycerin administration. Intracoronary ultrasound made it possible to rule out atherosclerotic involvement of the infarct-related artery. Subsequently, microvascular angina developed, which was confirmed by positron emission tomography. Vasospastic angina in combination with microvascular angina, MIBOCA with asthma attacks, were regarded as type 1 Kounis syndrome. Over the next 2 years, the patient received pathogenetic treatment, and no recurrent cardiovascular events were observed.Discussion. Lack of awareness about Kounis syndrome led to incomplete examination of the patient with MIBOCA and the prescription of pathogenetically unreasonable tehrapy, which could contribute to recurrent MI within 6 months.

Effects of the Dual FAAH/MAGL Inhibitor AKU-005 on Trigeminal Hyperalgesia in Male Rats.

The inhibition of endocannabinoid hydrolysis by enzymatic inhibitors may interfere with mechanisms underlying migraine-related pain. The dual FAAH/MAGL inhibitor AKU-005 shows potent inhibitory activity in vitro. Here, we assessed the effect of AKU-005 in a migraine animal model based on nitroglycerin (NTG) administration. Male rats were treated with AKU-005 (0.5 mg/kg, i.p.) or vehicle 3 h after receiving NTG (10 mg/kg, i.p.) or NTG vehicle. One hour later, rats were subjected to the open field test followed by the orofacial formalin test. At the end of the test, we collected serum samples for assessing calcitonin gene-related peptide (CGRP) levels as well as meninges, trigeminal ganglia, and brain areas to assess mRNA levels of CGRP and pro-inflammatory cytokines, and endocannabinoid and related lipid levels. AKU-005 reduced NTG-induced hyperalgesia during the orofacial formalin test but did not influence NTG-induced changes in the open field test. It significantly reduced serum levels of CGRP, CGRP, and pro-inflammatory cytokine mRNA levels in the meninges, trigeminal ganglia, and central areas. Surprisingly, AKU-005 caused no change in endocannabinoids and related lipids in the regions evaluated. The present findings suggest that AKU-005 may have anti-migraine effects by reducing CGRP synthesis and release and the associated inflammatory events. This effect, however, does not seem mediated via an interference with the endocannabinoid pathway.

Environmental enrichment alleviates hyperalgesia by modulating central sensitization in a nitroglycerin-induced chronic migraine model of mice

BackgroundChronic migraine (CM) is a debilitating neurofunctional disorder primarily affecting females, characterized by central sensitization. Central sensitization refers to the enhanced response to sensory stimulation, which involves changes in neuronal excitability, synaptic plasticity, and neurotransmitter release. Environmental enrichment (EE) can increase the movement, exploration, socialization and other behaviors of mice. EE has shown promising effects in various neurological disorders, but its impact on CM and the underlying mechanism remains poorly understood. Therefore, the purpose of this study was to determine whether EE has the potential to serve as a cost-effective intervention strategy for CM.MethodsA mouse CM model was successfully established by repeated administration of nitroglycerin (NTG). We selected adult female mice around 8 weeks old, exposed them to EE for 2 months, and then induced the CM model. Nociceptive threshold tests were measured using Von Frey filaments and a hot plate. The expression of c-Fos, calcitonin gene-related peptide (CGRP) and inflammatory response were measured using WB and immunofluorescence to evaluate central sensitization. RNA sequencing was used to find differentially expressed genes and signaling pathways. Finally, the expression of the target differential gene was investigated.ResultsRepeated administration of NTG can induce hyperalgesia in female mice and increase the expression of c-Fos and CGRP in the trigeminal nucleus caudalis (TNC). Early exposure of mice to EE reduced NTG-induced hyperalgesia in CM mice. WB and immunofluorescence revealed that EE inhibited the overexpression of c-Fos and CGRP in the TNC of CM mice and alleviated the inflammatory response of microglia activation. RNA sequencing analysis identified that several central sensitization-related signaling pathways were altered by EE. VGluT1, a key gene involved in behavior, internal stimulus response, and ion channel activity, was found to be downregulated in mice exposed to EE.ConclusionEE can significantly ameliorate hyperalgesia in the NTG-induced CM model. The mechanisms may be to modulate central sensitization by reducing the expression of CGRP, attenuating the inflammatory response, and downregulating the expression of VGluT1, etc., suggesting that EE can serve as an effective preventive strategy for CM.

Rapid Intravenous Glyceryl Trinitrate in Ischemic Damage (RIGID): A potential neuroprotection strategy for acute ischemic stroke (AIS) patients

Despite advances in intravenous thrombolysis and endovascular thrombectomy, numerous acute ischemic stroke survivors continue to experience various disability levels. The nitric oxide (NO) donor, Glyceryl Trinitrate (GTN), has been identified as a potential neuroprotective agent against ischemic damage. We evaluated the safety and feasibility of intravenous GTN in AIS patients. Subsequently, we conducted a secondary analysis to assess for possible efficacy of GTN as a neuroprotectant. We conducted a prospective, double-blind, randomized controlled trial in the Stroke Intervention & Translational Center (SITC) in Beijing Luhe Hospital, Capital Medical University (ChiCTR2100046271). AIS patients within 24 h of stroke onset were evenly divided into GTN or control groups (n = 20 each). The GTN group received intravenous GTN (5 mg in 50 ml saline at a rate of 0.4 mg/h for 12.5 h/day over 2 days), while controls were administered an equivalent volume of 0.9% saline. Both groups followed standard Stroke Guidelines for treatment. Safety measures focused on SBP<110 mmHg and headache occurrence. Efficacy was assessed via the 90-day modified rankin score (mRS) and the national institutes of health stroke score (NIHSS). Of the 40 AIS patients, baseline characteristics such as age, gender, risk factors, and pre-mRS scores showed no significant difference between the groups. Safety measures of SBP<110 mmHg and headache occurrence were comparable. Overall, 90-day mRS (1 vs. 1) and NIHSS (1 vs. 1) did not significantly differ between groups. However, the GTN-treated group had a benefit in enhancing NIHSS recovery (△NIHSS 4.5 vs. 3, p = 0.028), indicating that GTN may augment recovery. Subgroup analyses revealed a benefit in the GTN group at the 90-day NIHSS score and △NIHSS follow up for non-thrombolysis patients (1 vs. 2, p = 0.016; 5 vs. 2, p = 0.001). Moreover, the GTN group may benefit mild stroke patients in NIHSS score at 90 day and △NIHSS observed at 90 days (1 vs. 1, p = 0.025; 3 vs. 2 p = 0.002). Overall, while preliminary data suggest GTN might aid recovery in NIHSS improvement, the evidence is tempered due to sample size limitations. The RIGID study confirms the safety and feasibility of intravenous GTN administration for AIS patients. Preliminary data also suggest that the GTN group may provide improvement in NIHSS recovery compared to the control group. Furthermore, a potential benefit for non-thrombolysis patients and those with mild stroke symptoms was identified, suggesting a possible potential role as a tailored intervention in specific AIS subgroups. Due to the limited sample size, further larger RCT will be necessary to replicate these results. Trial Registrationwww.chictr.org.cn, identifier: ChiCTR2100046271.

Combination Administration of Heparin and Nitroglycerin for the Treatment of Polycaprolactone-Induced Intravascular Embolism: A Preclinical Investigation.

As a new-generation collagen stimulator, polycaprolactone (PCL) containing filler has been extensively applied in facial dermal fillers and other medical aesthetic fields. However, inadvertent intravascular injection of PCL may result in complications such as tissue edema, flap necrosis, and even blindness. To date, there is no effective treatment for PCL-induced intravascular embolism. The aim of this study was to identify a viable resolution for the embolism resulting from intravascular administration of PCL-containing fillers. Two different animal experiments were performed: (1) PCL-induced rat inferior epigastric arteries embolism, followed by gross observation, histological evaluation, and cytokines analysis from serum; and (2) PCL-induced rabbit auricular artery embolism, immediately treated with heparin and nitroglycerin. The ears were then evaluated by gross observation, Laser speckle imaging, in vivo imaging system (IVIS) imaging, and histological evaluation. Saline and hyaluronic acids (HA) were used as controls, hyaluronidase was used as a positive drug. In a rat model of inferior epigastric arteries embolism, both intravascular injection of HA and PCL resulted in flap necrosis, indicating that the filler-induced intravascular embolism can lead to serious complications. In a rabbit model of auricular artery embolism, the combination treatment of heparin and nitroglycerin resulted in a relative blood reperfusion recovery of 80% in the ischemic area of the PCL group on day 7 post-operation, which was comparable to that of the HA group treated with hyaluronidase. Histological analysis revealed that the administration of heparin and nitroglycerin significantly attenuated intravascular thrombosis formation and inflammatory cell aggregation. The combination of heparin and nitroglycerin effectively restores blood flow reperfusion in the intravascular embolization caused by PCL filler injection, alleviates local tissue edema and flap necrosis. These findings offer a novel approach for future clinical management of intravascular embolization with PCL-containing filler injection. This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Efficacy and Safety of Prehospital Diltiazem

Objective This study assesses the likelihood of clinical improvement and adverse events from EMS-administered diltiazem. Current prehospital protocols direct paramedics to administer diltiazem, a calcium channel blocker, to decrease the heart rate (HR) of symptomatic, hemodynamically stable patients with rapid atrial fibrillation. However, diltiazem can also cause systemic hypotension and bradycardia, which can precipitate end-organ injury. Methods To assess whether the rate control benefit of prehospital diltiazem outweighs the risk of adverse events, we conducted a retrospective chart review of all adult patients who received diltiazem from Maryland Advanced Life Support EMS clinicians between January 1, 2019, and March 31, 2022. Collected data included patient demographics, vital signs, diltiazem dose, transport times, administered medications, and procedures. The main outcomes were clinical improvement (HR <100 beats per minute or ≥20% decrease from the maximum HR) and adverse events (bradycardia or hypotension). Multivariable logistic regression was used for statistical analysis. Results During the study period, 2396 patients received prehospital diltiazem and 94% of these patients (n = 2254) were included in the study. Overall, 1414 (63.8%) patients improved clinically, 604 (27.3%) patients achieved rate control as defined by a HR of <100 beats per minute, and 78 patients (3.5%) experienced an adverse event. Patients over the age of 50 were less likely to clinically improve with diltiazem administration. Adverse events were more likely in patients with systolic blood pressures (SBP) less than 140 mmHg, patients with maximum HR of less than 120 beats per minute, and patients who received nitroglycerin. Conclusions Prehospital diltiazem is effective and safe for most patients. Adverse events are more likely in patients with baseline SBP less than 140 mmHg, HR less than 120 beats per minute, and concurrent nitroglycerin administration. Future opportunities for research include examining the relationship between adverse events and underlying etiology as well as investigating downstream outcomes.

Feasibility and Utility of Anatomical and Physiological Evaluation of Coronary Disease With Cardiac CT in Severe Aortic Stenosis (FUTURE-AS Registry): Rationale and Design

BackgroundCoronary artery disease (CAD) in patients with severe aortic stenosis (AS) is common and may be associated with worse outcomes. Computed tomography coronary angiography (CTCA) and fractional flow reserve derived from computed tomography (FFRCT) are tools for comprehensive coronary assessment. The utility and safety of CTCA and FFRCT in the work-up for transcatheter aortic valve replacement (TAVR) is not established, especially in an evolving landscape that involves younger TAVR patients. The FUTURE-AS Registry will assess the utility and safety of cardiac-optimized CTCA and FFRCT to evaluate CAD and guide referral for downstream invasive coronary angiography (ICA) in patients with severe AS being considered for TAVR. MethodsFUTURE-AS is an international, prospective, multicenter registry of patients with severe AS referred for TAVR being assessed for CAD with CTCA and FFRCT. The primary end point is the per-patient sensitivity and negative predictive value of CTCA and FFRCT for identifying anatomical and physiologically significant CAD compared to ICA and invasive FFR. The safety end point is the incidence of symptomatic hypotension or bradycardia requiring intervention following the administration of nitroglycerin or β-blocker medications. Feasibility end points include the incidence of noninterpretable CTCA scans and CTCA scans not adequate for FFR analysis. Other utility end points include specificity, positive predictive value, and accuracy of CTCA and FFRCT. Lastly, the potential of a CTCA and FFRCT guided strategy to defer pre-TAVR ICA will be assessed. ConclusionsFUTURE-AS will characterize the utility, safety, and feasibility of CTCA and FFRCT for coronary assessment pre-TAVR.

Nitroglycerin to Ameliorate Coronary Artery Spasm During Focal Pulsed-Field Ablation for Atrial Fibrillation

BackgroundIn treating atrial fibrillation, pulsed-field ablation (PFA) has comparable efficacy to conventional thermal ablation, but with important safety advantages: no esophageal injury or pulmonary vein stenosis, and rare phrenic nerve injury. However, when PFA is delivered in proximity to coronary arteries using a pentaspline catheter, which generates a broad electrical field, severe vasospasm can be provoked. ObjectivesThe authors sought to study the vasospastic potential of a focal PFA catheter with a narrower electrical field and develop a preventive strategy with nitroglycerin. MethodsDuring atrial fibrillation ablation, a focal PFA catheter was used for cavotricuspid isthmus ablation. Angiography of the right coronary artery (some with fractional flow reserve measurement) was performed before, during, and after PFA. Beyond no nitroglycerin (n = 5), and a few testing strategies (n = 8), 2 primary nitroglycerin administration strategies were studied: 1) multiple boluses (3-2 mg every 2 min) into the right atrium (n = 10), and 2) a bolus (3 mg) into the right atrium with continuous peripheral intravenous infusion (1 mg/min; n = 10). ResultsWithout nitroglycerin, cavotricuspid isthmus ablation provoked moderate-severe vasospasm in 4 of 5 (80%) patients (fractional flow reserve 0.71 ± 0.08). With repetitive nitroglycerin boluses, severe spasm did not occur, and mild-moderate vasospasm occurred in only 2 of 10 (20%). Using the bolus + infusion strategy, severe and mild-moderate spasm occurred in 1 and 3 of 10 patients (aggregate 40%). No patient had ST-segment changes. ConclusionsAblation of the cavotricuspid isthmus using a focal PFA catheter routinely provokes right coronary vasospasm. Pretreatment with high doses of parenteral nitroglycerin prevents severe spasm.

Unraveling the directional relationship of sleep and migraine-like pain.

Migraine and sleep disorders are common co-morbidities. Patients frequently link their sleep to migraine attacks suggesting a potential causal relationship between these conditions. However, whether migraine pain promotes or disrupts sleep or whether sleep disruption can increase the risk of migraine remains unknown. We assessed the potential impact of periorbital allodynia, a measure consistent with migraine-like pain, from multiple preclinical models on sleep quantity and quality. Additionally, we evaluated the possible consequences of sleep deprivation in promoting susceptibility to migraine-like pain. Following the implantation of electroencephalogram/electromyography electrodes to record sleep, mice were treated with either single or repeated systemic injections of nitroglycerin at the onset of their active phase (i.e. nocturnal awake period). Neither single nor repeated nitroglycerin affected the total sleep time, non-rapid eye movement sleep, rapid eye movement sleep, sleep depth or other measures of sleep architecture. To account for the possible disruptive effects of the surgical implantation of electroencephalogram/electromyography electrodes, we used immobility recordings as a non-invasive method for assessing sleep-wake behaviour. Neither single nor repeated nitroglycerin administration during either the mouse sleep (i.e. daylight) or active (i.e. night) periods influenced immobility-defined sleep time. Administration of an inflammatory mediator mixture onto the dura mater at either sleep or active phases also did not affect immobility-defined sleep time. Additionally, inhalational umbellulone-induced migraine-like pain in restraint-stressed primed mice did not alter immobility-defined sleep time. The possible influence of sleep disruption on susceptibility to migraine-like pain was evaluated by depriving female mice of sleep over 6 h with novel objects, a method that does not increase circulating stress hormones. Migraine-like pain was not observed following acute sleep deprivation. However, in sleep-deprived mice, subthreshold doses of systemic nitroglycerin or dural calcitonin gene-related peptide induced periorbital cutaneous allodynia consistent with migraine-like pain. Our data reveal that while migraine-like pain does not significantly disrupt sleep, sleep disruption increases vulnerability to migraine-like pain suggesting that a therapeutic strategy focused on improving sleep may diminish migraine attacks.

Hyperventilation testing in the diagnosis of vasospastic angina: A clinical review and meta-analysis.

Given the limited access to invasive vasospastic reactivity testing in Western Countries, there is a need to further develop alternative non-invasive diagnostic methods for vasospastic angina (VSA). Hyperventilation testing (HVT) is defined as a class IIa recommendation to diagnose VSA by the Japanese Society of Cardiology. In this systematic review and meta-analysis reported according to the PRISMA statement, we review the mechanisms, methods, modalities and diagnostic accuracy of non-invasive HVT for the diagnostic of VSA. A total of 106 articles published between 1980 and 2022 about VSA and HVT were included in the systematic review, among which 16 were included in the meta-analysis for diagnostic accuracy. Twelve electrocardiogram-HVT studies including 804 patients showed a pooled sensitivity of 54% (95% confidence intervals [CI]; 30%-76%) and a pooled specificity of 99% (95% CI; 88%-100%). Four transthoracic echocardiography-HVT studies including 197 patients revealed a pooled sensitivity of 90% (95% CI; 82%-94%) and a pooled specificity of 98% (95% CI; 86%-100%). Six myocardial perfusion imaging-HVT studies including 112 patients yielded a pooled sensitivity of 95% (95% CI; 63%-100%) and a pooled specificity of 78% (95% CI; 19%-98%). Non-invasive HVT resulted in a low rate of adverse events, ventricular arrhythmias being the most frequently reported, and were resolved with the administration of nitroglycerin. Non-invasive HVT offers a safe alternative with high diagnostic accuracy to diagnose VSA in patients with otherwise undiagnosed causes of chest pain.

Abstract 27: A Novel Adjuvant Strategy After Endovascular Therapy: Arterial Glyceryl Trinitrate in Acute Ischemic Stroke for Neuroprotection (AGAIN)

Introduction: Although mechanical thrombectomy (MT) demonstrates robust clinical efficacy in acute ischemic stroke (AIS), not all stroke patients benefit from successful reperfusion. The protective effect of NO donors has been shown to prevent ischemia-reperfusion injury through reduction of reactive oxygen species formation in cardiovascular studies. Glyceryl Trinitrate (GTN), a Food and Drug Administration-approved vasodilator, is one of the widely used exogenous NO donors used in the clinic and has been trialed for neuroprotection in AIS without successful clinical translation. The recent advances in MT for AIS have paved the way for promising new opportunities to supplementary neuroprotective therapies to patients after reperfusion. This study evaluated the safety, feasibility, and preliminary efficacy of intra-arterial administration of GTN after MT for neuroprotection. Methods: This is a prospective randomized controlled study (ID: ChiCTR2100045254). Eligible patients were randomized to receive 800μg GTN or same volume of normal saline through the catheter after recanalization. The primary outcome was symptomatic intracranial hemorrhage (sICH), while secondary outcomes included mortality, functional outcome, infarction volume, complications, and blood nitrate index (NOx). Results: A total of 40 patients were enrolled and randomized with no participants being lost to follow-up. There was no significant difference in the proportion of sICH between GTN and control groups. No significant difference was observed in mortality or rates of neurological deterioration and other complications. Favorable trends for both functional independence (mRS 0-2, 75.0% vs. 65.0%) at 90 days and reduction in final infarct volume (33.2 vs. 38.9 ml) have been observed in GTN group, although they did not reach the significant levels. Moreover, the concentration of blood NO X was increased (p&lt;0.05) at 2 hours after GTN administration (26.2 vs 18.0 μmol/l). Conclusion: The AGAIN study suggests intra-arterial administration of GTN post MT is safe and feasible in AIS patient. The discernible positive trends may be due to the raised NO X levels, which potentially highlight the mechanistic reinforcement for these observed benefits.