Iatrogenic intracranial hypotension secondary to subarachnoid-pleural fistula after transthoracic surgery for the treatment of lateral thoracic meningocele.

Subarachnoid-pleural fistula (SPF), a rare complication following transthoracic spinal surgery, results in the accumulation of cerebrospinal fluid (CSF) in the pleural space. Hindered spontaneous closure, attributed to negative pleural pressure, gives rise to CSF hypotension and subdural blood collections. Despite numerous reported cases, achieving consensus on management remains elusive. Treatment options encompass conservative measures, surgical repair, epidural blood patch, and diverse approaches such as multilayer dural closure or meningocele resection. Presented herein is a distinctive case following lateral thoracic meningocele surgery, where SPF-induced CSF hypotension found successful resolution through the innovative use of titanium hemostatic clips to occlude the meningocele. This novel approach, emphasizing the utility of titanium clips, deviates from conventional strategies. Surgical SPF exclusion, particularly leveraging titanium clips, emerges as a potential solution, effectively alleviating symptoms of CSF hypotension. The article also aims to present a personal experience, contributing an effective and alternative approach for the etiological treatment of thoracic meningocele.

Emotions observed during sessions of dialectical behavior therapy predict outcome for borderline personality disorder.

OBJECTIVE: We examined whether the emotions that clients experience within session are associated with treatment outcome in dialectical behavior therapy (DBT) for borderline personality disorder (BPD). METHOD: Participants were 52 adults who met criteria for BPD and were enrolled in a 12-month DBT treatment. The Classification of Affective-Meaning States, an observer-rated measure of discrete emotions, was used to code videos of individual DBT sessions. Raters coded three psychotherapy sessions for each participant: one session from each of the early, working, and late phases of psychotherapy. Self-report measures of BPD symptoms were used to assess treatment outcome. RESULTS: More emotional experience overall during the early phase predicted fewer BPD symptoms at 12-month treatment outcome, explaining 19% of the variance in symptoms. However, increases across treatment in global distress predicted higher levels of BPD (24% of the variance explained) and depression symptoms (15% explained) at termination. Increases in emotional flexibility (i.e., variation between states) from the early to working phase predicted fewer depressive symptoms at termination (14% explained). Self-compassion coded during the working phase also predicted a better treatment outcome (explaining 19%-34%). CONCLUSIONS: Clients' in-session emotional experiences predict treatment outcome 8-10 months later. Clients with BPD may benefit from more overall exploration of their emotional experiences early in DBT, as well as expression of self-compassion. Increases in nonspecific, intense negative affect anticipates poor prognosis, whereas increases in emotional flexibility during early treatment anticipates better prognosis. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Non-invasive physiological assessment of intermediate coronary stenoses from plain angiography through artificial intelligence: the STARFLOW system.

BACKGROUND: Despite evidence supporting use of fractional flow reserve (FFR) and instantaneous waves-free ratio (iFR) to improve outcome of patients undergoing coronary angiography (CA) and percutaneous coronary intervention, such techniques are still underused in clinical practice due to economic and logistic issues. OBJECTIVES: We aimed to develop an artificial intelligence (AI)-based application to compute FFR and iFR from plain CA. METHODS AND RESULTS: Consecutive patients performing FFR or iFR or both were enrolled. A specific multi-task deep network exploiting 2 projections of the coronary of interest from standard CA was appraised. Accuracy of prediction of FFR/iFR of the AI model was the primary endpoint, along with sensitivity and specificity. Prediction was tested both for continuous values and for dichotomous classification (positive/negative) for FFR or iFR. Subgroup analyses were performed for FFR and iFR.A total of 389 patients from 5 centers were enrolled. Mean age was 67.9 ± 9.6 and 39.2% of patients were admitted for acute coronary syndrome. Overall, the accuracy was 87.3% (81.2-93.4%), with a sensitivity of 82.4% (71.9-96.4%) and a specificity of 92.2% (90.4-93.9%). For FFR, accuracy was 84.8% (77.8-91.8%), with a sensitivity of 81.9% (69.4-94.4%) and a specificity of 87.7% (85.5-89.9%), while for iFR accuracy was 90.2% (86.0-94.6%), with a sensitivity of 87.2% (76.6-97.8%) and a specificity of 93.2% (91.7-94.7%, all confidence intervals 95%). CONCLUSION: The presented machine-learning based tool showed high accuracy in prediction of wire-based FFR and iFR.

Development of machine learning models for fractional flow reserve prediction in angiographically intermediate coronary lesions.

BACKGROUND: Fractional flow reserve (FFR) represents the gold standard in guiding the decision to proceed or not with coronary revascularization of angiographically intermediate coronary lesion (AICL). Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. OBJECTIVES: We sought to develop machine learning (ML) models based on clinical, angiographic and OCT variables for predicting FFR. METHODS: Data from a multicenter, international, pooled analysis of individual patient's level data from published studies assessing FFR and OCT on the same target AICL were collected through a dedicated database to train (n = 351) and validate (n = 151) six two-class supervised ML models employing 25 clinical, angiographic and OCT variables. RESULTS: A total of 502 coronary lesions in 489 patients were included. The AUC of the six ML models ranged from 0.71 to 0.78, whereas the measured F1 score was from 0.70 to 0.75. The ML algorithms showed moderate sensitivity (range: 0.68-0.77) and specificity (range: 0.59-0.69) in detecting patients with a positive or negative FFR. In the sensitivity analysis, using 0.75 as FFR cut-off, we found a higher AUC (0.78-0.86) and a similar F1 score (range: 0.63-0.76). Specifically, the six ML models showed a higher specificity (0.71-0.84), with a similar sensitivity (0.58-0.80) with respect to 0.80 cut-off. CONCLUSIONS: ML algorithms derived from clinical, angiographic, and OCT parameters can identify patients with a positive or negative FFR.

Angiography-derived physiological patterns of coronary artery disease: implications with post-stenting physiology and long-term clinical outcomes.

BACKGROUND: Physiological patterns of coronary artery disease (CAD) have emerged as potential determinants of functional results of percutaneous coronary interventions (PCI) and of vessel-oriented clinical outcomes (VOCE). OBJECTIVES: In this study, we evaluated the impact of angiography-derived physiological patterns of CAD on post-PCI functional results and long-term clinical outcomes. METHODS: Pre-PCI angiography-derived fractional flow reserve (FFR) virtual pullbacks were quantitatively interpreted and used to determine the physiological patterns of CAD. Suboptimal post-PCI physiology was defined as an angiography-derived FFR value ≤ 0.91. The primary endpoint was the occurrence of VOCE at the longest available follow-up. RESULTS: Six hundred fifteen lesions from 516 patients were stratified into predominantly focal (n = 322, 52.3%) and predominantly diffuse (n = 293, 47.7%). Diffuse pattern of CAD was associated with lower post-PCI angiography-derived FFR values (0.91 ± 0.05 vs. 0.94 ± 0.05; p = 0.001) and larger rate of suboptimal post-PCI physiology (43.0 vs. 22.7%; p = 0.001), as compared to focal CAD. At the median follow-up time of 37 months (33-58), post-PCI suboptimal physiology was related to a higher risk of VOCE (16.2% vs. 7.6%; HR: 2.311; 95% CI 1.410-3.794; p = 0.0009), while no significant difference was noted according to baseline physiological pattern. In diffuse disease, the use of intracoronary imaging was associated with a lower incidence of long-term VOCE (5.1% vs 14.8%; HR: 0.313, 95% CI 0.167-0.614, p = 0.030). CONCLUSIONS: Suboptimal post-PCI physiology is observed more often in diffusely diseased arteries and it is associated with higher risk of VOCE at follow-up. The use of intravascular imaging might improve clinical outcomes in the setting of diffuse CAD.

Age and Vasodilator Response to Different Hyperemic Agents: Adenosine versus Contrast Medium.

Background: Age-related remodelling has the potential to affect the microvascular response to hyperemic stimuli. However, its precise effects on the vasodilatory response to adenosine and contrast medium, as well as its influence on fractional flow reserve (FFR) and contrast fractional flow reserve (cFFR), have not been previously investigated. We investigate the impact of age on these indices. Methods: We extrapolated data from the post-revascularization optimization and physiological evaluation of intermediate lesions using fractional flow reserve (PROPHET-FFR) and The Multi-center Evaluation of the Accuracy of the Contrast MEdium INduced Pd/Pa RaTiO in Predicting (MEMENTO) studies. Only lesions with a relevant vasodilatory response to adenosine and contrast medium were considered of interest. A total of 2080 patients, accounting for 2294 pressure recordings were available for analysis. The cohort was stratified into three age terciles. Age-dependent correlations with FFR, cFFR, distal pressure/aortic pressure (Pd/Pa) and instantaneous wave-free ratio (iFR) were calculated. The vasodilatory response was calculated in 1619 lesions (with both FFR and cFFR) as the difference between resting and hyperaemic pressure ratios and correlated with aging. The prevalence of FFR-cFFR discordance was assessed. Results: Age correlated positively to FFR (r = 0.062, p = 0.006), but not with cFFR (r = 0.024, p = 0.298), Pd/Pa (r = -0.015, p = 0.481) and iFR (r = -0.026, p = 0.648). The hyperemic response to adenosine (r = -0.102, p ≤ 0.0001) and to contrast medium (r = -0.076, p = 0.0023) showed a negative correlation with age. When adjusted for potential confounders, adenosine induced hyperaemia was negatively associated with age (p = 0.04 vs p = 0.08 for cFFR). Discordance decreased across age terciles (14.64% vs 12.72% vs 10.12%, p = 0.032). Conclusions: As compared to adenosine, contrast induced hyperaemia appeared to be less affected by age. cFFR may be considered a more stable and reproducible tool to assess epicardial stenosis in elderly patients. Clinical Trial Registration: PROPHET-FFR STUDY, Clinicaltrials.gov (NCT05056662).

A Novel Hemodynamic Index Characterizing Mitral Regurgitation Undergoing Transcatheter Edge-to-Edge Repair: The MPF.

Background: Hemodynamic impact of residual mitral regurgitation (MR) after transcatheter edge-to-edge repair (TEER) is not always univocally measured by transesophageal echocardiographic (TEE) assessment alone. When analyzing TEER procedure result, operators often encounter discrepancy between TEE guidance and invasive hemodynamic monitoring. Objectives: This study sought to investigate the role of invasive hemodynamic monitoring during mitral valve TEER procedure on top of TEE guidance. Methods: We analyzed 78 patients with moderate-to-severe or severe MR who underwent TEER. Mitral pulse pressure fraction (MPF) was extracted from intraprocedural continuous left atrial pressure monitoring. Twenty-three patients with the same grade of MR not undergoing TEER were included as a control group. At follow-up, clinical and functional status in the majority of patients undergoing TEER were reassessed by NYHA classification and the 12-item Kansas City Cardiomyopathy Questionnaire (KCCQ). Results: TEER significantly reduced MR burden on both TEE guidance and invasive hemodynamic monitoring. Post-TEER MPF was significantly reduced compared to both pre-TEER setting (P < 0.001) and control group (P < 0.001). At follow-up, while MR reduction assessed by TEE was associated with an improved functional status in terms of the 12-item KCCQ but not of NYHA classification, a greater reduction in MPF was associated with a significant amelioration of both NYHA classification (P = 0.036) and 12-item KCCQ (P = 0.032). Conclusions: MPF could provide an immediate estimate of the real hemodynamic impact of MR and a prompt prediction of the functional improvement after TEER.

Optical Coherence Tomography Measures Predicting Fractional Flow Reserve: The OMEF Study.

Background: Optical coherence tomography (OCT) allows to carefully characterize coronary plaque morphology and lumen dimensions. We sought to evaluate the value of OCT in predicting fractional flow reserve (FFR). Methods: We performed a multicenter, international, pooled analysis of individual patient-level data from published studies assessing FFR and OCT on the same vessel. Data from stable or unstable patients who underwent both FFR and OCT of the same coronary artery were collected through a dedicated database. Predefined OCT parameters were minimum lumen area (MLA), percentage area stenosis (%AS), and presence of thrombus or plaque rupture. Primary end point was FFR ≤0.80. Secondary outcome was the incidence of major adverse cardiac events in patients not undergoing revascularization based on negative FFR (>0.80). Results: A total of 502 coronary lesions in 489 patients were included. A significant correlation was observed between OCT-MLA and FFR values (R = 0.525; P < .001), and between OCT-%AS and FFR values (R = -0.482; P < .001). In Receiver operating characteristic analysis, MLA <2.0 mm2 showed a good discriminative power to predict an FFR ≤0.80 (AUC, 0.80), whereas %AS >73% showed a moderate discriminative power (AUC, 0.73). When considering proximal coronary segments, the best OCT cutoff values predicting an FFR ≤0.80 were MLA <3.1 mm2 (AUC, 0.82), and %AS >61% (AUC, 0.84). In patients with a negative FFR not revascularized, the combination of lower MLA and higher %AS had a trend toward worse outcome (which was statistically significant in the analysis restricted to proximal vessels). Conclusions: OCT lumen measures (MLA, %AS) may predict FFR, and different cutoffs are needed for proximal vessels.

Broadening the evidentiary basis for clinical practice guidelines: Recommendations from qualitative psychotherapy researchers.

To improve the provision of psychotherapy, many countries have now established clinical practice guidelines for the treatment of specific disorders and mental health concerns. These guidelines have typically been based on evidence from meta-analyses of randomized clinical trials with minimal consideration of findings from qualitative research designs. This said, there has been growing interest in incorporating qualitative research in guideline development processes from both stakeholders and guideline development bodies. In this international collaboration, 19 qualitative psychotherapy researchers from 10 countries articulated the benefits of including qualitative findings within the guideline development process and generated recommendations for guideline developers. The underlying question of this report was "Why and how should qualitative research be used in efforts to develop guidance for psychotherapy practice?" The advantages of reviewing qualitative findings included the ability to identify treatment patterns at the level of in-session dynamics, cultural contexts, interpersonal relationships, and internal experiences, thereby creating guidance that is responsive to clients' needs in the moment-to-moment therapy process. Recommendations are offered at the systemic level (e.g., guideline formation processes, methods of education, research funding priorities). Also, methodological advice is offered for guideline developers when selecting to incorporate qualitative research in the implementation of an expanded guideline development process. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Multivessel revascularization in non-ST segment elevation acute coronary syndromes: A systematic review and meta-analysis of 182,798 patients.

BACKGROUND: Patients experiencing non-ST segment elevation acute-coronary-syndromes (NSTE-ACS) often present with multivessel-coronary-artery-disease (MVD). An immediate complete multivessel revascularization (MVR) - within the index hospitalization - may be considered the default therapeutic strategy, although its risk-to-benefit profile has not been definitively established through dedicated clinical trials. METHODS: A systematic review and meta-analysis, adhering to MOOSE and PRISMA guidelines, was conducted to assess studies comparing immediate MVR versus a conservative culprit-only revascularization (COR) in NSTE-ACS with MVD. The main endpoints were all-cause death, major adverse cardiovascular events (MACE) and non-fatal myocardial infarction (MI). The incidence of any revascularization or further percutaneous-coronary-interventions (PCIs) were also collected. The primary analyses for the main endpoints were conducted on propensity-matched groups only. RESULTS: A total of 22 studies (182,798 patients) were identified. 7 studies, encompassing 11,372 patients, were included in the primary analysis of propensity score-matched groups. Immediate MVR significantly increased (28%) survival (OR 0.72, 95% CI 0.58-0.90, P < 0.01) along with a 35% reduction in MACE (OR 0.65, 95% CI 0.47-0.88, P = 0.01) and a 60% decrease in MI (OR 0.40, 95% CI 0.25-0.63, P < 0.01) during a mean 3-years follow-up compared to the propensity score-matched COR group. Results were consistent in the unmatched analyses. CONCLUSIONS: This meta-analysis supports an immediate MVR for improving clinical outcomes in patients with NSTE-ACS and MVD as compared to a conservative immediate COR. These data prompt further evaluations regarding optimal strategies in the pursuit of MVR, including patient selection, revascularization modality, and assessment methods of revascularization completeness.

Ischemia with non-obstructive coronary artery (INOCA): Non-invasive versus invasive techniques for diagnosis and the role of #FullPhysiology.

Ischemia with non-obstructive coronary arteries (INOCA) is an increasingly recognized entity. It encompasses different pathophysiological subtypes (i.e., endotypes), including coronary microvascular dysfunction (CMD), vasospastic angina (VSA) and mixed entities resulting from the variable combination of both. Diagnosing INOCA and precisely characterizing the endotype allows for accurate medical treatment and has proven prognostic implications. A breadth of diagnostic technique is available, ranging from non-invasive approaches to invasive coronary angiography adjuvated by functional assessment and provocative tests. This review summarizes the strength and limitations of these methodologies and provides the rationale for the routine referral for invasive angiography and functional assessment in this subset of patients.

Influence of Pathophysiologic Patterns of Coronary Artery Disease on Immediate Percutaneous Coronary Intervention Outcomes.

BACKGROUND: Diffuse coronary artery disease affects the safety and efficacy of percutaneous coronary intervention (PCI). Pathophysiologic coronary artery disease patterns can be quantified using fractional flow reserve (FFR) pullbacks incorporating the pullback pressure gradient (PPG) calculation. This study aimed to establish the capacity of PPG to predict optimal revascularization and procedural outcomes. METHODS: This prospective, investigator-initiated, single-arm, multicenter study enrolled patients with at least one epicardial lesion with an FFR ≤0.80 scheduled for PCI. Manual FFR pullbacks were used to calculate PPG. The primary outcome of optimal revascularization was defined as an FFR ≥0.88 after PCI. RESULTS: A total of 993 patients with 1044 vessels were included. The mean FFR was 0.68±0.12, PPG 0.62±0.17, and the post-PCI FFR was 0.87±0.07. PPG was significantly correlated with the change in FFR after PCI (r=0.65 [95% CI, 0.61-0.69]; P<0.001) and demonstrated excellent predictive capacity for optimal revascularization (area under the receiver operating characteristic curve, 0.82 [95% CI, 0.79-0.84]; P<0.001). FFR alone did not predict revascularization outcomes (area under the receiver operating characteristic curve, 0.54 [95% CI, 0.50-0.57]). PPG influenced treatment decisions in 14% of patients, redirecting them from PCI to alternative treatment modalities. Periprocedural myocardial infarction occurred more frequently in patients with low PPG (<0.62) compared with those with focal disease (odds ratio, 1.71 [95% CI, 1.00-2.97]). CONCLUSIONS: Pathophysiologic coronary artery disease patterns distinctly affect the safety and effectiveness of PCI. PPG showed an excellent predictive capacity for optimal revascularization and demonstrated added value compared with an FFR measurement. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04789317.

Three-Year Clinical Impact of Murray Law-Based Quantitative Flow Ratio and OCT- or FFR-Guidance in Angiographically Intermediate Coronary Lesions.

BACKGROUND: The FORZA trial (FFR or OCT Guidance to Revascularize Intermediate Coronary Stenosis Using Angioplasty) prospectively compared the use of fractional flow reserve (FFR) or optical coherence tomography (OCT) for treatment decisions and percutaneous coronary intervention (PCI) optimization in patients with angiographically intermediate coronary lesions. Murray law-based quantitative-flow-ratio (µQFR) is a novel noninvasive method for the computation of FFR. In the present study, we evaluated the clinical impact of µQFR, FFR, or OCT guidance in FORZA trial lesions at 3-year follow-up. METHODS: µQFR was assessed at baseline and, in the case of a decision to intervene, after (FFR- or OCT-guided) PCI. The baseline µQFR was considered the final µQFR for deferred lesions, and post-PCI µQFR value was taken as final for stented lesions. The primary end point was target vessel failure ([TVF]; cardiac death, target-vessel-related myocardial infarction, and target-vessel-revascularization) at a 3-year follow-up. RESULTS: A total of 419 vessels (199 OCT-guided and 220 FFR-guided) were included in the FORZA trial. µQFR was evaluated in 256 deferred lesions and 159 treated lesions (98 OCT-guided PCI and 61 FFR-guided PCI). In treated lesions, post-PCI µQFR was higher in OCT-group compared with FFR-group (median, 0.93 versus 0.91; P=0.023), and the post-PCI µQFR improvement was greater in FFR-group (0.14 versus 0.08; P<0.0001). At 3-year follow-up, OCT- and FFR-guided treatment decisions resulted in comparable TVF rate (6.7% versus 7.9%; P=0.617). Final µQFR was the only predictor of TVF. µQFR ≤0.89 was associated with 3× increase in TVF (11.6% versus 3.7%; P=0.004). PCI was a predictor of higher final µQFR (odds ratio, 0.22 [95% CI, 0.14-0.34]; P<0.001). CONCLUSIONS: In vessels with angiographically intermediate coronary lesions, OCT-guided PCI resulted in comparable clinical outcomes as FFR-guided PCI. µQFR estimated at the end of diagnostic or interventional procedure predicted 3-year TVF. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT01824030.

Predicting the response to acetylcholine in ischemia or infarction with non-obstructive coronary arteries: The ABCD score.

BACKGROUND AND AIMS: Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. METHODS: We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). RESULTS: 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652-0.754,p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626-0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. CONCLUSIONS: The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score.

Comprehensive Angiography-Derived Functional Assessment of Epicardial and Microvascular Coronary Disease. Correlation With Non-invasive Myocardial Stress Imaging.

Coronary angiography (CA) is poorly correlated with non-invasive myocardial stress imaging (NSI) and myocardial ischemia is often observed in patients with unobstructed coronary arteries. Moreover, the diagnostic performance of combined epicardial and microcirculatory angiography-derived physiological assessment and its correlation with NSI remains unknown. A total of 917 coronary vessels in 319 patients who underwent both CA and NSI were included in this multicenter observational retrospective analysis. Quantitative flow ratio (QFR) and angiography-derived index of microcirculatory resistance (IMRangio) analyses were performed to estimate coronary epicardial and microcirculatory function respectively. NSI demonstrated evidence of myocardial ischemia in 76% of the cases. IMRangio (36 [22 to 50] vs 29 [21 to 41], p <0.001) was significantly higher and QFR (0.92 [0.78 to 0.99] vs 0.97 [0.91 to 0.99], p <0.001) was significantly lower in vessels subtending ischemic territories. Overall, the diagnostic accuracy of QFR was moderate (area under the curve of receiver operating characteristic [AUCROC] 0.632 [95% confidence interval [CI] 0.589 to 0.674], p <0.0001) but it was higher in patients with normal microcirculatory function (AUCROC = 0.726 [95% CI 0.669 to 0.784], p <0.0001, p Value for AUCROC comparison = 0.009). Combined QFR/IMRangio assessment provided incremental diagnostic performance compared with the evaluation of epicardial or microcirculatory districts in isolation (p Value for AUC comparison <0.0001) and it was able to identify the predominant mechanism of myocardial ischemia in 77% of the patients with positive NSI. Our study suggests the value of a combined angiography-derived assessment of epicardial and microvascular function for the definition of the predominant mechanism of myocardial ischemia in patients with suspected coronary artery disease.

Coronary Spasm Testing with Acetylcholine: A Powerful Tool for a Personalized Therapy of Coronary Vasomotor Disorders.

Coronary vasomotor disorders (CVD) are characterized by transient hypercontraction of coronary vascular smooth muscle cells, leading to hypercontraction of epicardial and/or microvascular coronary circulation. CVDs play a relevant role in the pathogenesis of ischemia, angina and myocardial infarction with non-obstructive coronary arteries. Invasive provocative testing with intracoronary Acetylcholine (ACh) administration is the gold standard tool for addressing CVD, providing relevant therapeutic and prognostic implications. However, safety concerns preclude the widespread incorporation of the ACh test into clinical practice. The purpose of this review is to shed light on the pathophysiology underlying CVD and on the clinical role of the ACh test, focusing on safety profile and prognostic implications. We will also discuss contemporary evidence on the management of CVD and the role of the ACh test in driving a personalized approach of patients with CVD.

"The INOCA-IT: Rationale and design of a multicenter registry investigating ischemia in patients with non-obstructive coronary artery (INOCA) disease in Italy".

BACKGROUND: Ischemia with non-obstructive coronary artery (INOCA) disease is being progressively acknowledged as one of the pathophysiological mechanisms of chronic coronary syndrome (CCS) in an increasingly wide range of clinical pictures. Although the research has already begun to move towards a defined diagnostic pathway and a specific medical therapy for this disease, at present it remains a clinical challenge, especially if not thoroughly investigated. METHODS AND RESULTS: The INOCA IT Multicenter Registry RF-2019-12369486 is a prospective, multicentric, non-randomized, single-arm, open label clinical study which aims to evaluate the efficacy of a stratified diagnostic and therapeutic approach on adverse events prevention and symptom relief in Italian patients with INOCA disease. The study population includes patients with a clinical presentation of CCS for angina and/or positive stress test for myocardial ischemia and evidence of non-obstructive coronary artery disease (CAD) at coronary angiography. In these patients a complete invasive coronary physiology assessment is performed with the guidewire-based measurement of coronary flow reserve (CFR) and index of microvascular resistance (IMR), followed by acetylcholine (ACh) spasm provocation test. On the basis of the results of coronary function testing, patients are stratified into different INOCA endotypes (coronary microvascular disease, vasospastic angina, microvascular spasm, non-cardiac chest pain) and given a tailored medical therapy in accordance with the latest scientific evidence. At one year follow-up the impact of such a target therapy on angina class and quality of life, as well as on cardiovascular adverse events (hospitalization and coronary revascularization) is evaluated. CONCLUSIONS: The INOCA-IT Multicenter Registry will inform clinicians on sex-specific prevalence of INOCA in Italy and will show the impact of a stratified diagnostic and therapeutic approach on symptoms burden and prognosis of INOCA patients.

Impact of thrombus aspiration on left ventricular remodeling and function in patients with ST-segment elevation myocardial infarction: A meta-analysis of randomized controlled trials.

BACKGROUND: Routine thrombus aspiration (TA) does not improve clinical outcomes in patients with ST-segment-elevation myocardial infarction (STEMI), although data from meta-analyses suggest that patients with high thrombus burden may benefit from it. The impact of TA on left ventricular (LV) functional recovery and remodeling after STEMI remains controversial. We aimed to pool data from randomized controlled trials (RCTs) on the impact of TA on LV function and remodeling after primary percutaneous coronary intervention (pPCI). METHODS: PubMed and CENTRAL databases were scanned for eligible studies. Primary outcome measures were: LV ejection fraction (LVEF), LV end diastolic volume (LVEDV), LV end systolic volume (LVESV) and wall motion score index (WMSI). A primary pre-specified subgroup analysis was performed comparing manual TA with mechanical TA. RESULTS: A total of 28 studies enrolling 4990 patients were included. WMSI was lower in TA group than in control (mean difference [MD] -0.11, 95% confidence interval [CI] -0.19 to -0.03). A greater LVEF (MD 1.91, 95% CI 0.76 to 3) and a smaller LVESV (MD -6.19, 95% CI -8.7 to -3.6) were observed in manual TA group compared to control. Meta regressions including patients with left anterior descending artery (LAD) involvement showed an association between TA use and the reduction of both LVEDV and LVESV (z = -2.13, p = 0.03; z = -3.7, p < 0.01) and the improvement in myocardial salvage index (z = 2.04, p = 0.04). CONCLUSION: TA is associated with improved LV function. TA technique, total ischemic time and LAD involvement appears to influence TA benefit on post-infarction LV remodeling.

Early treatment of type II SMA slows rate of progression of scoliosis.

BACKGROUND: Type II spinal muscular atrophy (SMA) often leads to scoliosis in up to 90% of cases. While pharmacological treatments have shown improvements in motor function, their impact on scoliosis progression remains unclear. This study aims to evaluate potential differences in scoliosis progression between treated and untreated SMA II patients. METHODS: Treatment effect on Cobb's angle annual changes and on reaching a 50° Cobb angle was analysed in treated and untreated type II SMA patients with a minimum 1.5-year follow-up. A sliding cut-off approach identified the optimal treatment subpopulation based on age, Cobb angle and Hammersmith Functional Motor Scale Expanded at the initial visit. Mann-Whitney U-test assessed statistical significance. RESULTS: There were no significant differences in baseline characteristics between the untreated (n=46) and treated (n=39) populations. The mean Cobb angle variation did not significantly differ between the two groups (p=0.4). Optimal cut-off values for a better outcome were found to be having a Cobb angle <26° or an age <4.5 years. When using optimal cut-off, the treated group showed a lower mean Cobb variation compared with the untreated group (5.61 (SD 4.72) degrees/year vs 10.05 (SD 6.38) degrees/year; p=0.01). Cox-regression analysis indicated a protective treatment effect in reaching a 50° Cobb angle, significant in patients <4.5 years old (p=0.016). CONCLUSION: This study highlights that pharmacological treatment, if initiated early, may slow down the progression of scoliosis in type II SMA patients. Larger studies are warranted to further investigate the effectiveness of individual pharmacological treatment on scoliosis progression in this patient population.