Spontaneous coronary artery dissection: an unpredictable event.

Spontaneous coronary artery dissection (SCAD) is an under-recognized cause of acute coronary syndrome that predominantly affects women in adulthood and is the leading cause of acute myocardial infarction in pregnancy. The most common clinical presentation is ST-segment elevation myocardial infarction (STEMI) or non-STEMI, followed by cardiogenic shock (∼2%), sudden cardiac death (0.8% in autopsy series), cardiac arrest, ventricular arrhythmias (∼5%), and Takotsubo syndrome. The prevalence of SCAD in the general population is largely uncertain due to underdiagnosis. Oral contraceptives, post-menopausal therapy, and infertility treatments are recognized associated factors. The pathological substrates (fibromuscular dysplasia) and triggers (especially emotional stress) are commonly present in affected women. The few cases with a precise genetic aetiology occur in the context of syndromic and non-syndromic connective tissue diseases. The only true certainty in SCAD is the overwhelming prevalence in women. The first event as well as the recurrence (up to 30%, which varies depending on the definition) is largely unpredictable. The treatment strategy is highly individualized and requires extensive additional study in order to optimize outcomes and prevent major adverse cardiovascular events in affected individuals. We have known about SCAD for nearly a century, but we still do not know how best to prevent, diagnose, and treat it, making SCAD a highly important and unmet clinical need.

Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes.

BACKGROUND: Conflicting evidence exists on the efficacy and safety of bivalirudin administered as part of percutaneous coronary intervention (PCI) in patients with an acute coronary syndrome. METHODS: We randomly assigned 7213 patients with an acute coronary syndrome for whom PCI was anticipated to receive either bivalirudin or unfractionated heparin. Patients in the bivalirudin group were subsequently randomly assigned to receive or not to receive a post-PCI bivalirudin infusion. Primary outcomes for the comparison between bivalirudin and heparin were the occurrence of major adverse cardiovascular events (a composite of death, myocardial infarction, or stroke) and net adverse clinical events (a composite of major bleeding or a major adverse cardiovascular event). The primary outcome for the comparison of a post-PCI bivalirudin infusion with no post-PCI infusion was a composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events. RESULTS: The rate of major adverse cardiovascular events was not significantly lower with bivalirudin than with heparin (10.3% and 10.9%, respectively; relative risk, 0.94; 95% confidence interval [CI], 0.81 to 1.09; P=0.44), nor was the rate of net adverse clinical events (11.2% and 12.4%, respectively; relative risk, 0.89; 95% CI, 0.78 to 1.03; P=0.12). Post-PCI bivalirudin infusion, as compared with no infusion, did not significantly decrease the rate of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events (11.0% and 11.9%, respectively; relative risk, 0.91; 95% CI, 0.74 to 1.11; P=0.34). CONCLUSIONS: In patients with an acute coronary syndrome, the rates of major adverse cardiovascular events and net adverse clinical events were not significantly lower with bivalirudin than with unfractionated heparin. The rate of the composite of urgent target-vessel revascularization, definite stent thrombosis, or net adverse clinical events was not significantly lower with a post-PCI bivalirudin infusion than with no post-PCI infusion. (Funded by the Medicines Company and Terumo Medical; MATRIX ClinicalTrials.gov number, NCT01433627.).

Assessing MICRO-vascular resistances via IMR to predict outcome in STEMI patients with multivessel disease undergoing primary PCI (AMICRO): Rationale and design of a prospective multicenter clinical trial.

BACKGROUND: In STEMI patients treated with primary percutaneous coronary angioplasty (PPCI) the evaluation of coronary microcirculatory resistance index (IMR) predict the extent of microvascular damage and left ventricular (LV) remodeling. However, the impact of IMR on the clinical outcome after PPCI in patients with multivessel disease (MVD) remains unsettled. AIM: We designed a prospective multicenter controlled clinical trial to evaluate the prognostic value of IMR in terms of clinical outcome and left ventricular remodeling in STEMI patients with MVD undergoing PPCI. METHODS AND DESIGN: The study will involve 242 patients with MVD defines as the presence of at least a non-culprit lesion of >50% stenosis at index coronary angiography. Both fractional flow reserve (FFR) and IMR will be measured in the infarct-related artery (IRA) after successful PPCI. Measurements of FFR and IMR will be repeated in the IRA and performed in the non-culprit vessels at staged angiography. The non-culprit vessel lesions will be treated only in the presence of a FFR<0.75. A 2D echocardiographic evaluation of the left ventricular (LV) volumes and ejection fraction will be performed before hospital discharge and at 1-year follow-up. The primary end-point of the study will be the composite of cardiovascular death, re-hospitalization for heart failure and resuscitation or appropriate ICD shock during 1-year of follow-up. Secondary end-points will be the impact of IMR in predicting LV remodeling during follow-up and correlations between IMR and ST-segment resolution. Other secondary endpoints will be need for new revascularization, stent thrombosis and re-infarction of the non-culprit vessels territory. IMPLICATIONS: If IMR significantly correlates with differences in outcome and LV remodeling, it will emerge as a potential prognostic index after PPCI in patients with MVD.

Radial versus femoral access in patients with acute coronary syndromes undergoing invasive management: a randomised multicentre trial.

BACKGROUND: It is unclear whether radial compared with femoral access improves outcomes in unselected patients with acute coronary syndromes undergoing invasive management. METHODS: We did a randomised, multicentre, superiority trial comparing transradial against transfemoral access in patients with acute coronary syndrome with or without ST-segment elevation myocardial infarction who were about to undergo coronary angiography and percutaneous coronary intervention. Patients were randomly allocated (1:1) to radial or femoral access with a web-based system. The randomisation sequence was computer generated, blocked, and stratified by use of ticagrelor or prasugrel, type of acute coronary syndrome (ST-segment elevation myocardial infarction, troponin positive or negative, non-ST-segment elevation acute coronary syndrome), and anticipated use of immediate percutaneous coronary intervention. Outcome assessors were masked to treatment allocation. The 30-day coprimary outcomes were major adverse cardiovascular events, defined as death, myocardial infarction, or stroke, and net adverse clinical events, defined as major adverse cardiovascular events or Bleeding Academic Research Consortium (BARC) major bleeding unrelated to coronary artery bypass graft surgery. The analysis was by intention to treat. The two-sided α was prespecified at 0·025. The trial is registered at ClinicalTrials.gov, number NCT01433627. FINDINGS: We randomly assigned 8404 patients with acute coronary syndrome, with or without ST-segment elevation, to radial (4197) or femoral (4207) access for coronary angiography and percutaneous coronary intervention. 369 (8·8%) patients with radial access had major adverse cardiovascular events, compared with 429 (10·3%) patients with femoral access (rate ratio [RR] 0·85, 95% CI 0·74-0·99; p=0·0307), non-significant at α of 0·025. 410 (9·8%) patients with radial access had net adverse clinical events compared with 486 (11·7%) patients with femoral access (0·83, 95% CI 0·73-0·96; p=0·0092). The difference was driven by BARC major bleeding unrelated to coronary artery bypass graft surgery (1·6% vs 2·3%, RR 0·67, 95% CI 0·49-0·92; p=0·013) and all-cause mortality (1·6% vs 2·2%, RR 0·72, 95% CI 0·53-0·99; p=0·045). INTERPRETATION: In patients with acute coronary syndrome undergoing invasive management, radial as compared with femoral access reduces net adverse clinical events, through a reduction in major bleeding and all-cause mortality. FUNDING: The Medicines Company and Terumo.

Ultrasound-Guided Ethanol Percutaneous Ablation Versus Rescue Surgery in Patients With Locoregional Recurrence of Papillary Thyroid Cancer.

OBJECTIVES: Neck recurrence of papillary thyroid cancer (PTC) is frequently detected after initial surgery. The management of these lesions may include rescue surgery (RS) or minimally invasive techniques in selected patients, but comparative studies evaluating the effectiveness and safety of these techniques are lacking. In this paper, we compared ultrasound-guided ethanol ablation (EA) in selected patients to RS in a matched cohort. METHODS: We retrospectively compared 41 patients and 41 matched PTC patients without known distant metastases, who underwent ultrasound-guided EA or RS (matched reference group), who had 63 and 75 thyroid bed and/or lymph node confirmed PTC recurrences during a median follow-up of 72.8 and 89.6 months, respectively. The primary outcome was time until structural recurrence, compared using Kaplan-Meier survival curves. The secondary outcomes included time until biochemical recurrence, plasma thyroglobulin (Tg) levels, American Thyroid Association (ATA) response-to-therapy categories by the last available observation, and treatment-derived complications in each group. RESULTS: No significant differences were found between the EA and RS groups for time until structural recurrence (log-rank test, P=0.94). The time until biochemical recurrence was also similar (P=0.51); and the plasma Tg concentration reduction and proportions of patients in the ATA reclassification categories were also similar. A significantly higher proportion of patients in the RS group presented treatment-derived complications (29.27% vs. 9.75%, P<0.05). CONCLUSION: In this retrospective analysis, the treatment of PTC neck recurrence with EA in selected patients was comparable to RS in a matched reference group for the long-term risk of structural or biochemical relapse, but with a lower risk of treatment-derived complications. These. RESULTS: support the effectiveness and safety of this minimally invasive technique in the management of selected patients with recurrent PTC.

Age-standardized incidence, mortality rate, and trend changes of thyroid cancer in the Balearic Islands during the 2000-2020 period: a population-based study.

Objective: Global thyroid cancer (TC) incidence is growing worldwide, but great heterogenicity exists among published studies, and thus, population-specific epidemiological studies are needed to adequate health resources and evaluate the impact of overdiagnosis. Methods: We conducted a Public Health System database retrospective review of TC incident cases from 2000 to 2020 in the Balearic Islands region and evaluated age-standardized incidence rate (ASIR), age at diagnosis, gender distribution, tumor size and histological subtype, mortality rate (MR), and cause of death. Estimated annual percent changes (EAPCs) were also evaluated and data from the 2000-2009 period were compared to the 2010-2020 period when neck ultrasound (US) was routinely performed by clinicians at Endocrinology Departments. Results: A total of 1387 incident cases of TC were detected. Overall, ASIR (×105) was 5.01 with a 7.82% increment in EAPC. A significant increase in the 2010-2020 period was seen for ASIR (6.99 vs 2.82, P < 0.001) and age at diagnosis (52.11 vs 47.32, P < 0.001) compared to the 2000-2009 period. A reduction in tumor size (2.00 vs 2.78 cm, P < 0.001) and a 6.31% increase in micropapillary TC (P < 0.05) were also seen. Disease-specific MR remained stable at 0.21 (×105). The mean age at diagnosis for all mortality groups was older than survivors (P < 0.001). Conclusion: The incidence of TC has grown in the 2000-2020 period in the Balearic Islands, but MR has not changed. Beyond other factors, a significant contribution of overdiagnosis to this increased incidence is likely due to changes in the routine management of thyroid nodular disease and increased availability of neck US.

Validation of a Contemporary Acute Kidney Injury Risk Score in Patients With Acute Coronary Syndrome.

BACKGROUND: A simple, contemporary risk score for the prediction of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) was recently updated, although its external validation is lacking. OBJECTIVES: The aim of this study was to validate the updated CA-AKI risk score in a large cohort of acute coronary syndrome patients from the MATRIX (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX) trial. METHODS: The risk score identifies 4 risk categories for CA-AKI. The primary endpoint was to appraise the receiver-operating characteristics of an 8-component and a 12-component CA-AKI model. Independent predictors of Kidney Disease Improving Global Outcomes-based acute kidney injury and the impact of CA-AKI on 1-year mortality and bleeding were also investigated. RESULTS: The MATRIX trial included 8,201 patients with complete creatinine values and no end-stage renal disease. CA-AKI occurred in 5.5% of the patients, with a stepwise increase of CA-AKI rates from the lowest to the highest of the 4 risk categories. The receiver-operating characteristic area under the curve was 0.67 (95% CI: 0.64-0.70) with model 1 and 0.71 (95% CI: 0.68-0.74) with model 2. CA-AKI risk was systematically overestimated with both models (Hosmer-Lemeshow goodness-of-fit test: P < 0.05). The 1-year risks of all-cause mortality and bleeding were higher in CA-AKI patients (HR: 7.03 [95% CI: 5.47-9.05] and HR: 3.20 [95% CI: 2.56-3.99]; respectively). There was a gradual risk increase for mortality and bleeding as a function of the CA-AKI risk category for both models. CONCLUSIONS: The updated CA-AKI risk score identifies patients at incremental risks of acute kidney injury, bleeding, and mortality. (Minimizing Adverse Haemorrhagic Events by Transradial Access Site and Systemic Implementation of angioX [MATRIX]; NCT01433627).

Coronary calcification in patients presenting with acute coronary syndromes: insights from the MATRIX trial.

AIMS: The role of coronary calcification on clinical outcomes among different revascularization strategies in patients presenting with acute coronary syndromes (ACSs) has been rarely investigated. The aim of this investigation is to evaluate the role of coronary calcification, detected by coronary angiography, in the whole spectrum of patients presenting with acute ACS. METHODS AND RESULTS: The present study was a post hoc analysis of the MATRIX programme. The primary endpoint was major adverse cardiovascular events (MACE), defined as the composite of all-cause mortality, myocardial infarction (MI), or stroke up to 365 days. Among the 8404 patients randomized in the MATRIX trial, data about coronary calcification were available in 7446 (88.6%) and therefore were included in this post hoc analysis. Overall, 875 patients (11.7%) presented with severe coronary calcification, while 6571 patients (88.3%) did not present severe coronary calcification on coronary angiography. Fewer patients with severe coronary calcification underwent percutaneous coronary intervention whereas coronary artery bypass grafting or medical therapy-only was more frequent compared with patients without severe calcification. At 1-year follow-up, MACE occurred in 237 (27.1%) patients with severe calcified coronary lesions and 985 (15%) patients without severe coronary calcified lesions [hazard ratio (HR) 1.91; 95% confidence interval (CI) 1.66-2.20, P < 0.001]. All-cause mortality was 8.6% in patients presenting with and 3.7% in those without severe coronary calcification (HR 2.38, 1.84-3.09, P < 0.001). Patients with severe coronary calcification incurred higher rate of MI (20.1% vs. 11.5%, HR 1.81; 95% CI 1.53-2.1, P < 0.001) and similar rate of stroke (0.8% vs. 0.6%, HR 1.35; 95% CI 0.61-3.02, P = 0.46). CONCLUSION: Patients with ACS and severe coronary calcification, as compared to those without, are associated with worse clinical outcomes irrespective of the management strategy.

Barriers associated with emergency medical service activation in patients with ST-segment elevation acute coronary syndromes.

Many ST-segment elevation acute coronary syndrome (STEACS) patients fail to activate the Emergency Medical System (EMS), with possible dramatic consequences. Prior studies focusing on barriers to EMS activation included patients with any acute coronary syndrome (ACS) without representation of southern European populations. We aimed to investigate the barriers to EMS call for patients diagnosed for STEACS in Italy. A prospective, single-center, survey administered to all patients treated with primary percutaneous coronary intervention for STEACS in a tertiary hospital in northern Italy from 01/06/2018 to 31/05/2020. The questionnaire was filled out by 293 patients. Of these, 191 (65.2%) activated the EMS after symptoms onset. The main reasons for failing to contact EMS were the perception that the symptoms were unrelated to an important health problem (45.5%) and that a private vehicle is faster than EMS to reach the hospital (34.7%). Patients who called a private doctor after symptoms onset did not call EMS more frequently than those who did not and 30% of the patients who did not call the EMS would still act in the same way if a new episode occurred. Previous history of cardiovascular disease was the only predictor of EMS call. Information campaigns are urgently needed to increase EMS activation in case of suspected STEACS and should be primary focused on patients without cardiovascular history, on the misperception that a private vehicle is faster than EMS activation, and on the fact that cardiac arrest occurs early and may be prevented by EMS activation.

One-year results from the Assessing MICRO-vascular resistances via IMR to predict outcome in ST-elevation myocardial infarction patients with multivessel disease undergoing primary PCI (AMICRO) trial.

Background: In ST-elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary angioplasty (PPCI) the index of microcirculatory resistance (IMR) correlates to the extent of myocardial damage and left ventricular (LV) function recovery. Data on the IMR time-course and impact on clinical outcome in STEMI patients with multi-vessel disease (MVD) are scarce. Aims: We designed a prospective, multicenter clinical trial to assess the infarct-related artery (IRA)-IMR in STEMI patients with MVD undergoing PPCI and to explore its potential in relationship with outcome and LV remodeling. Methods: The study enrolled 242 STEMI patients with MVD. Both fractional flow reserve (FFR) and IMR of the IRA were assessed after successful PPCI. Then, FFR/IMR measurements were repeated in the IRA at a staged angiography, and FFR-guided angioplasty was performed in non-IRA lesions. The primary endpoint was the composite of cardiovascular death, re-infarction, re-hospitalization for heart failure, resuscitation or appropriate ICD shock at 1-year follow-up. Results: A significant improvement of IRA-IMR values (from 47.9 to 34.2, p < 0.0001) was observed early after PPCI. Staged FFR-guided angioplasty was performed in 102 non-IRA lesions. We failed to find a correlation between IRA-IMR, clinical events and LV remodeling. Notwithstanding, in patients with anterior STEMI an inverse correlation between initial IMR values and LV function at follow-up was observed. Conclusion: After successful PPCI, a significant proportion of patients with STEMI and MVD had coronary microvascular dysfunction as assessed by IMR that recovered early after reperfusion. Higher IMR values predicted lack of improvement of LV function only in anterior STEMI. Clinical trial registration: https://clinicaltrials.gov/, identifier [NCT02325973].

Complete Revascularization and One-Year Survival with Good Neurological Outcome in Patients Resuscitated from an Out-of-Hospital Cardiac Arrest.

Background. The survival benefit of complete versus infarct-related artery (IRA)-only revascularization during the index hospitalization in patients resuscitated from an out-of-hospital cardiac arrest (OHCA) with multivessel disease is unknown. Methods. We considered all the OHCA patients prospectively enrolled in the Lombardia Cardiac Arrest Registry (Lombardia CARe) from 1 January 2015 to 1 May 2021 who underwent coronary angiography (CAG) at the Fondazione IRCCS Policlinico San Matteo (Pavia). Patients' prehospital, angiographical and survival data were reviewed. Results. Out of 239 patients, 119 had a multivessel coronary disease: 69% received IRA-only revascularization, and 31% received a complete revascularization: 8 during the first procedure and 29 in a staged-procedure after a median time of 5 days [IQR 2.5−10.3]. The complete revascularization group showed significantly higher one-year survival with good neurological outcome than the IRA-only group (83.3% vs. 30.4%, p < 0.001). After correcting for cardiac arrest duration, shockable presenting rhythm, peak of Troponin-I, creatinine on admission and the need for circulatory support, complete revascularization was independently associated with the probability of death and poor neurological outcome [HR 0.3 (95%CI 0.1−0.8), p = 0.02]. Conclusions. This observation study shows that complete myocardial revascularization during the index hospitalization improves one-year survival with good neurological outcome in patients resuscitated from an OHCA with multivessel coronary disease.

Clinical governance of patients with acute coronary syndromes.

AIMS: Using the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy. METHODS AND RESULTS: Administrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852-7867) ACS patients were admitted and 5107 were enrolled-i.e. a consecutive index of 69.6% (95% CI 64.9-74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7-24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40-0.89) and an adjusted NNT of 65 (95% CI: 44-250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7-71.4%), HR of 0.50 (95% CI: 0.38-0.66), and NNT of 98 (95% CI: 79-145). CONCLUSION: A comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery. REGISTRATION: ClinicalTrials.Gov ID NCT04255537.

Importance and limits of pre-hospital electrocardiogram in patients with ST elevation myocardial infarction undergoing percutaneous coronary angioplasty.

BACKGROUND: The purpose of this study is to present data on the effects of pre-hospital electrocardiogram (PH-ECG) on the outcome of ST elevation myocardial infarction (STEMI) patients treated with percutaneous coronary angioplasty (PCI) included in a registry undertaken in the Italian region of Lombardy. Pre-hospital 12-lead electrocardiogram is recommended by current guidelines in order to achieve faster times to reperfusion in patients with STEMI. METHODS: The registry includes 3901 STEMI patients who underwent primary PCI over an 18-month period. RESULTS: Mean age was 63 ± 12 years. Admission through the emergency medical system (EMS) occurred in 1603 patients (40%): they were older, more frequently had previous MI, TIMI flow = 0 at entry and were more frequently in Killip class >1 than patients who were not admitted through the EMS. Among the patients admitted through the EMS, PH-ECG was obtained in 475 patients (12%). These patients had less frequently an anterior MI, but more frequently had absence of TIMI flow at entry than patients whose ECG was not teletransmitted. Moreover, they had a significantly shorter first medical contact-to-balloon time and a trend toward a lower 30-day death rate (5.3% vs 7.9 %, p = 0.06). However, only patients in Killip class 2-3 had a significantly lower mortality when the diagnostic ECG was transmitted, whereas no difference was found in Killip class 1 or Killip class 4 patients. CONCLUSIONS: In this registry, PH-ECG significantly decreased first medical contact-to-balloon time. Attempts to achieve faster reperfusion times should be undertaken, as this may result in improved outcome, particularly in patients with mild to moderate symptoms of heart failure.

Hallucinations and REM sleep behaviour disorder in Parkinson's disease: dream imagery intrusions and other hypotheses.

REM sleep behaviour disorder (RBD) is a REM sleep-related parasomnia which may be considered a "dissociated state of wakefulness and sleep", given that conflicting elements of REM sleep (dreaming) and of wakefulness (sustained muscle tone and movements) coexist during the episodes, leading to motor and behavioural manifestations reminiscent of an enacted dream. RBD has been reported in association with α-synucleinopathies: around a third of patients with Parkinson's disease (PD) have full-blown RBD. Recent data indicate that PD patients with RBD are more prone to hallucinations than PD patients without this parasomnia. However it is still not clear why RBD in PD is associated with an increased prevalence of VHs. Data exist which suggest that visual hallucinations in PD may be the result of untimely intrusions of REM visual imagery into wakefulness. RBD, which is characterised by a REM sleep dissociation pattern, might be a condition that particularly favours such intrusions. However, other hypotheses may be advanced. In fact, deficits in attentional, executive, visuoperceptual and visuospatial abilities have been documented in RBD and found to occur far more frequently in PD with RBD than in PD without RBD. Neuropsychological deficits involving visual perception and attentional processes are thought to play an important role in the pathophysiology of VHs. On this basis, RBD in PD could be viewed as a contributory risk factor for VHs.

Oral aspirin or low dose of intravenous lysine acetylsalicylate in ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention.

AIM: To compare the pharmacodynamic effect of an oral loading dose of 'noncoated' ASA 300 mg vs. an intravenous bolus injection of lysine acetylsalicylate 150 mg in patients with STEMI undergoing pPCI. METHODS: This was a prospective single-center, open label, pharmacodynamic study, including nonconsecutive patients presenting at our catheterization laboratory with STEMI undergoing pPCI and not receiving ASA within the previous 7 days. Pharmacodynamic analyses were performed at five time points: baseline, and 1, 2, 4 and 12 h after the loading dose, and measured as ASA reaction units (ARU) by the Verify Now System. An ARU more than 550 was considered as nonresponsiveness to study drugs. The primary end point was the different rate of patients with ARU more than 550 at 2 h after the loading dose of oral vs. intravenous ASA. Secondary end points included the comparison of ARU more than 550 at the other time points and the comparison of continuous ARU at each time point. RESULTS: The study was planned with a sample size of 68 patients, but it was prematurely stopped due to slow enrollment after the inclusion of 23 patients, 12 randomized to oral ASA and 11 to intravenous lysine acetylsalicylate. At 2 h the rate of patients with ARU more than 550 was numerically but not significantly higher in patients receiving oral ASA as compared with intravenous lysine acetylsalicylate (33 vs. 14.2%; Δ -0.19, 95% confidence interval -0.59-0.21, P = 0.58). The difference over time was NS (P = 0.98), though the prevalence of ARU more than 550 was higher at the other time points. Both routes of administration reduced ARU values over time, though with no overall significant difference between profiles (P overall = 0.48). CONCLUSION: In patients with STEMI undergoing pPCI the rate of nonresponsiveness to ASA was not different comparing an oral 'noncoated' loading dose of ASA with an intravenous bolus injection of lysine acetylsalicylate. However, as patient enrollment was prematurely terminated, this study is underpowered to draw a definite conclusion.

Total Lesion Glycolysis Improves Tumor Burden Evaluation and Risk Assessment at Diagnosis in Hodgkin Lymphoma.

Hodgkin lymphoma (HL) is a hematological malignancy with an excellent prognosis. However, we still need to identify those patients that could experience failed standard frontline chemotherapy. Tumor burden evaluation and standard decisions are based on Ann Arbor (AA) staging, but this approach may be insufficient in predicting outcomes. We aim to study new ways to assess tumor burden through volume-based PET parameters to improve the risk assessment of HL patients. We retrospectively analyzed 101 patients with HL from two hospitals in the Balearic Islands between 2011 and 2018. Higher metabolic tumor volume (MTV) and total lesion glycolysis (TLG) were significantly associated with a higher incidence of III-IV AA stages, B-symptoms, hypoalbuminemia, lymphopenia, and higher IPS. Standardized uptake value (SUVmax) was significantly related to AA stage and hypoalbuminemia. We found that TLG or the combination of SUVmax, TLG, and MTV significantly improved the risk assessment when compared to AA staging. We conclude that TLG is the best single PET/CT-related tumor-load parameter that significantly improves HL risk assessment when compared to AA staging. If confirmed in a larger and validated sample, this information could be used to modify standard frontline therapy and justifies the inclusion of TLG inside an HL prognostic score.

Intensifying platelet inhibition with tirofiban in poor responders to aspirin, clopidogrel, or both agents undergoing elective coronary intervention: results from the double-blind, prospective, randomized Tailoring Treatment with Tirofiban in Patients Showing Resistance to Aspirin and/or Resistance to Clopidogrel study.

BACKGROUND: Inhibition of platelet aggregation after aspirin or clopidogrel intake varies greatly among patients, and previous studies have suggested that poor response to oral antiplatelet agents may increase the risk of thrombotic events, especially after coronary angioplasty. Whether this reflects suboptimal platelet inhibition per se, which might benefit from more potent antiplatelet agents such as tirofiban, is unknown. METHODS AND RESULTS: We screened 1277 patients to enroll 93 aspirin, 147 clopidogrel, and 23 dual poor responders, based on a point-of-care assay, who underwent elective coronary angioplasty at 10 European sites for stable or low-risk unstable coronary artery disease. Patients were randomly assigned in a double-blind manner to receive either tirofiban (n=132) or placebo (n=131) on top of standard aspirin and clopidogrel therapy. The primary end point, consisting of troponin I/T elevation at least 3 times the upper limit of normal, was attained in 20.4% (n=27) in the tirofiban group compared with 35.1% (n=46) in the placebo group (relative risk, 0.58; 95% confidence interval, 0.39 to 0.88; P=0.009). The rate of major adverse cardiovascular events within 30 days in the tirofiban group also was reduced (3.8% versus 10.7%; P=0.031). The overall incidence of bleeding was low, likely explained by a substantial use of the transradial approach, and did not differ between the 2 groups. CONCLUSIONS: In low-risk patients according to clinical presentation who had poor responsiveness to standard oral platelet inhibitors via a point-of-care assay, intensified platelet inhibition with tirofiban lowers the incidence of myocardial infarction after elective coronary intervention.

The angiotensin-converting enzyme insertion/deletion polymorphism modifies the clinical outcome in patients with Pompe disease.

PURPOSE: The insertion/deletion polymorphism of angiotensin-converting enzyme may influence muscle properties. We examined whether Pompe disease clinical manifestations, which are known to be highly variable among late-onset patients, may be modulated by angiotensin-converting enzyme polymorphism. METHODS: We included 38 patients with late-onset Pompe disease, aged 44.6 +/- 19.8 years. We compared the distribution of angiotensin-converting enzyme polymorphism according to demographic and disease parameters. RESULTS: The distribution of angiotensin-converting enzyme polymorphism was in line with the general population, with 16% of patients carrying the II genotype, 37% carrying the DD genotype, and the remaining patients with the ID genotype. The three groups did not differ in mean age, disease duration, Walton score, and other scores used to measure disease severity. The DD polymorphism was associated with earlier onset of disease (P = 0.041), higher creatine kinase levels at diagnosis (P = 0.024), presence of muscle pain (P = 0.014), and more severe rate of disease progression (P = 0.037, analysis of variance test for interaction). DISCUSSION: These findings suggest a potential role of angiotensin-converting enzyme polymorphism in modulating Pompe disease phenotype and prognosis.

Complex paroxysmal nocturnal behaviors in Parkinson's disease.

Complex paroxysmal nocturnal motor behavioral disorders (CPNBs) are frequently reported in patients with Parkinson's disease (PD). REM sleep behavior disorder (RBD) is reported in at least a third of PD patients, although CPNB episodes can also occur on arousal from NREM sleep. It is important to establish the nature of CPNBs occurring in PD, as the different types have different neurobiological significance and clinical importance, and also different treatments. Ninety-six PD patients with and without CPNBs were submitted to overnight in-hospital video-polysomnography. Of these, 76 (47 men) were included in the study analysis: these were patients in whom it was possible to establish the presence or absence of CPNBs and to obtain a clear-cut diagnosis of the nature of the CPNBs reported. The CPNBs were found to be RBD episodes in 39 cases (87%) and nonRBD episodes in 6 (13%) (arousal-related episodes arising from NREM sleep in 3 cases and from REM sleep in 2 cases, parasomnia overlapping syndrome in 1 case). In 4 of the 6 subjects with nonRBD episodes, these occurred upon arousal at the end of an obstructive apnoeic event. Our data confirm that CPNBs in PD are, in most cases, RBD episodes. However, arousal-related episodes accounted for 13% of the CPNBs observed in our sample and occurred in close temporal association with sleep-disordered breathing (SDB). The arousal system is defective in extrapyramidal diseases due to neurodegenerative changes involving the brain stem reticular network; against this background, a trigger effect of SDB on CPNBs, through induction of abrupt arousal, may be hypothesized.

Dobutamine stress echocardiography for assessing the role of dynamic intraventricular obstruction in left ventricular ballooning syndrome.

BACKGROUND: Dynamic intraventricular obstruction has been observed in patients with left ventricular ballooning syndrome (LVBS) and has been hypothesized as a possible mechanism of the syndrome. The aim of this study was to assess the prevalence and significance of dynamic intraventricular obstruction in patients with LVBS. METHODS AND RESULTS: Dobutamine stress echocardiography was carried out in 22 patients with LVBS (82% apical), all women, aged 68 +/- 9 years. At baseline 1 patient had a > 30 mmHg LV gradient; during stress a LV gradient > 30 mm Hg developed in 6/21 patients (28%) and was caused by systolic anterior motion of the mitral valve in the 3 patients with severe gradient (mean 116 +/- 29 mmHg), who developed mitral regurgitation and impaired apical wall motion and by obstruction at mid-ventricular level in the other 3 with a moderate gradient (mean 46 +/- 16 mmHg). Compared with patients without obstruction those with obstruction had a greater mean septal thickness (11.6 +/- .6 vs 9.8. +/- 3, p < .01), a higher prevalence of septal hypertrophy (71% vs 7%, p < .005) and a higher peak wall motion score index (1.62 +/- .4 vs 1.08 +/- .4, p < .01). CONCLUSION: Spontaneous or dobutamine-induced dynamic LV obstruction is documented in 32% of patients with LVBS, is correlated with the presence of septal hypertrophy and may play a role in the development of LVBS in this subset of patients. In those without septal hypertrophy a dynamic obstruction is rarely induced with dobutamine and is unlikely to be a major pathogenetic factor of the syndrome.