Nonfatal Recurrence Research Articles

Comparison of myocardial infarction with non-obstructive coronary arteries (MINOCA) versus type 2 MI with NSTEMI presentation; an Italian observation study

Abstract Funding Acknowledgements None. Background In the last decades, NSTEMI, is the predominant phenotype of myocardial infarction (MI) and many NSTEMI patients(pts) have a non-obstructive CAD. NSTEMI, represents an umbrella for many different conditions with distinct underlying pathogenesis and exhibits significant gender discrepancies and survival differences. Further, in absence of non-obstructive CAD, pts could be wrongly comforted about their prognosis. Purpose In this study, we compared the characteristics and the prognosis of pts with MINOCA and type 2 MI with non-obstructive CAD. The primary outcome was a composite of all-cause mortality, non-fatal MI, hospitalization for heart failure (HF) and transitory ischemic attack or non-fatal stroke. Methods Were screened 18223 pts with MI, who underwent coronary angiography between 2005 and 2022. Among them, 7815 pts had NSTEMI presentation, of which 693 pts (9%) had a non-obstructive CAD. After reviewing the angiographic data and clinical presentation, 155 pts were excluded because they belonged to one of the categories known as "MINOCA mimichers" (Fig 1). Five hundred and thirty eight pts with MI, NSTEMI presentation and with non-obstructive CAD were included in the final cohort: 301 (56%) had MINOCA and 237 pts (44%) had type 2 MI (Fig 1). Results The mean age of the population was 68 years, and females were predominant in both groups. MINOCA pts were younger, more frequently had adverse events during pregnancy and endocrine disorders. Pts with type 2 MI were more likely to have typical CV risk factors and comorbidities such as CKD and HF. Pts with type 2 MI had a worse diastolic function, a more dilated left atrium and left ventricle(LV), and non-coronary distribution of regional LV wall-motion abnormalities. At initial clinical presentation, the MINOCA group had typical chest pain upon awakening or at night, responsive to nitrates, while type 2 MI were more often to present with dyspnea, palpitations, and with higher blood pressure. Coronary vasospasm and embolization were the most common identified aetiologies in MINOCA pts while tachyarrhythmias were the most common trigger of type 2 MI, followed by hypertensive crisis. The final model of the predictors of MINOCA at multivariate logistic regression analysis listed in Fig 2, yielded an AUC of 0.865, p<0.01 at ROC analysis(Fig 2a). These variables were used for the generation of nomogram for MINOCA prediction(Fig 2b). During the median follow-up of 61 months (IQR 34.2-100.35), pts with MINOCA had a significantly better survival rate; 135 of 538 pts (25.1%) reached the primary combined endpoint(Fig 3a). The primary end-point was mainly driven by the all-cause mortality, followed by HF hospitalization, non-fatal stroke, non-fatal MI recurrence. Results of Cox multivariable analysis are presented in Fig 3b. Conclusions MINOCA cohort was associated with unconventional risk factors and had a better prognosis compared to T2 MI, which is closer to the classical AMI-CAD.

The Vienna Prediction Model for identifying patients at low risk of recurrent venous thromboembolism: a prospective cohort study.

Patients with unprovoked venous thromboembolism (VTE) have a high recurrence risk, and guidelines suggest extended-phase anticoagulation. Many patients never experience recurrence but are exposed to bleeding. The aim of this study was to assess the performance of the Vienna Prediction Model (VPM) and to evaluate if the VPM accurately identifies these patients. In patients with unprovoked VTE, the VPM was performed 3 weeks after anticoagulation withdrawal. Those with a predicted 1-year recurrence risk of ≤5.5% were prospectively followed. Study endpoint was recurrent VTE over 2 years. A total of 818 patients received anticoagulation for a median of 3.9 months. 520 patients (65%) had a predicted annual recurrence risk of ≤5.5%. During a median time of 23.9 months, 52 patients had non-fatal recurrence. The recurrence risk was 5.2% [95% confidence interval (CI) 3.2-7.2] at 1 year and 11.2% (95% CI 8.3-14) at 2 years. Model calibration was adequate after 1 year. The VPM underestimated the recurrence risk of patients with a 2-year recurrence rate of >5%. In a post-hoc analysis, the VPM's baseline hazard was recalibrated. Bootstrap validation confirmed an ideal ratio of observed and expected recurrence events. The recurrence risk was highest in men with proximal deep-vein thrombosis or pulmonary embolism and lower in women regardless of the site of incident VTE. In this prospective evaluation of the performance of the VPM, the 1-year rate of recurrence in patients with unprovoked VTE was 5.2%. Recalibration improved identification of patients at low recurrence risk and stratification into distinct low-risk categories.

Recurrent Acute Necrotizing Encephalopathy with underlying RANBP2 mutation

Objective N/A. Background Acute necrotizing encephalopathy (ANE) is a rapidly progressive encephalopathy that can occur in otherwise healthy children after common viral infections such as influenza and parainfluenza. Most ANE is sporadic and nonrecurrent (isolated ANE). We report a case of recurrent acute necrotizing encephalitis in a boy with an identified RANBP2 mutation, which is known to account for the majority of recurrent ANE cases. Design/Methods CASE REPORT Our patient is a 13-year-old boy with no significant medical or developmental history and no family history of neurodevelopmental disorders.He had his first episode at 15 months of agewhich manifested as irritability, non-responsiveness and was diagnosed as acute disseminated encephalomyelitis (ADEM) and subsequently had 4 additional episodes of ANE at ages 4,4.5,5, and 10. After his third episode, testing for RANBP2 was performed and found to be positive. His typical presentation includes fever, staring spells, nystagmus and altered sensorium during these episodes typically within 24 hours of febrile-illness. He has had multiple triggering viral infections identified including adenovirus, influenza A and parainfluenza. Ultimately his ANE episodes were managed with iv pulse steroid therapy and IVIG.With treatment he has had a slow but nearcomplete recovery, including radiological resolution. He does have mild cognitive impairment and learning difficulties which have persisted. Results N/A. Conclusions This patient has had numerous episodes of ANE triggered by infection that have responded well to acute management without prophylactic immunomodulation. This is, to our knowledge, themost non-fatal recurrences that have been reported with this condition. Our case suggests that multiple relapses are possible in patients with ANE and early diagnosis and treatment of the episodic encephalopathy would result in improved outcomes. Our case raises the consideration of prophylactic immunotherapy but also demonstrates a relatively positive outcome with a watchful management approach. Keywords: acute necrotizing encephalopathy.

Association Between Plasma Trimethyllysine and Prognosis of Patients With Ischemic Stroke.

BackgroundTrimethyllysine, a trimethylamine N‐oxide precursor, has been identified as an independent cardiovascular risk factor in acute coronary syndrome. However, limited data are available to examine the role of trimethyllysine in the population with stroke. We aimed to examine the relationship between plasma trimethyllysine levels and stroke outcomes in patients presenting with ischemic stroke or transient ischemic attack.Methods and ResultsData of 10 027 patients with ischemic stroke/transient ischemic attack from the CNSR‐III (Third China National Stroke Registry) and 1‐year follow‐up data for stroke outcomes were analyzed. Plasma levels of trimethyllysine were measured with mass spectrometry. The association between trimethyllysine and stroke outcomes was analyzed using Cox regression models. Mediation analysis was performed to examine the mediation effects of risk factors on the associations of trimethyllysine and stroke outcomes. Elevated trimethyllysine levels were associated with increased risk of cardiovascular death (quartile 4 versus quartile 1: adjusted hazard ratio [HR], 1.72; 95% CI, 1.03–2.86) and all‐cause mortality (quartile 4 versus quartile 1: HR, 1.97; 95% CI, 1.40–2.78) in multivariate Cox regression model. However, no associations were found between trimethyllysine and nonfatal stroke recurrence or nonfatal myocardial infarction. Trimethyllysine was associated with cardiovascular death independent of trimethylamine N‐oxide. Both estimated glomerular filtration rate and hs‐CRP (high‐sensitivity C‐reactive protein) had significant mediation effects on the association of trimethyllysine with cardiovascular death, with a mediation effect of 37.8% and 13.4%, respectively.ConclusionsElevated trimethyllysine level is associated with cardiovascular death among patients with ischemic stroke/transient ischemic attack. Mediation analyses propose that trimethyllysine contributes to cardiovascular death through inflammation and renal function, suggesting a possible pathomechanistic link.

Contemporary Implications of ECG to Activation Time on Long-term Outcomes in Patients With ST-Segment Elevation Myocardial Infarction Treated With Primary Percutaneous Coronary Intervention

PurposeThe prognosis of door to balloon time (DBT) after primary percutaneous coronary intervention (PPCI) in ST-segment elevation myocardial infarction (STEMI) has been extensively studied. However, the clinical implications of the ECG to activation time (EAT), as a component of DBT, on long-term outcomes are less well established. This study evaluates the association of EAT with major adverse cardiovascular events (MACEs) in more contemporary patients undergoing PPCI and investigates factors that influence EAT. MethodsA total of 1082 consecutive patients with STEMI who underwent PPCI from 2013 to 2019 were classified into 3 groups according to EAT: EAT ≤30 minutes, EAT of 30 to 60 minutes, and EAT >60 minutes. We analyzed the incidence of MACEs, including all-cause death, nonfatal recurrence of MI, or nonfatal stroke during a median follow-up of 37 months. FindingsThe median EAT was 58 minutes (interquartile range, 44–80 minutes), which explained 90% of the variability in DBT and had the strongest correlation with DBT (r = 0.95, P < 0.001). Achieving an EAT of ≤30 minutes resulted in a 94.1% chance of achieving a DBT ≤90 minutes. The incidence of MACEs had a concurrent increase with increased EAT (10.2% for EAT ≤30 minutes, 14.3% for EAT of 30–60 minutes, and 17.3% for EAT >60 minutes; P = 0.027) that was driven by more mortality (4.2% for EAT ≤30 minutes, 6.9% for EAT of 30–60 minutes, and 9.8% for EAT >60 minutes; P = 0.020). An EAT >30 minutes was independently associated with risk-adjusted long-term MACEs (hazard ratio = 1.99; 95% CI, 1.07–3.69; P = 0.030). Critically ill status in emergency department (P = 0.001) and time required for consent of revascularization (P < 0.001) were significantly associated with delayed EAT. ImplicationsAchieving an EAT ≤30 minutes was key to achieving the guideline-recommended target time of DBT in contemporary practice. As a strong driver of overall DBT, EAT >30 minutes was associated with worse clinical outcome in patients with STEMI undergoing PPCI. These data suggest that efforts to minimize EAT are needed to reduce long-term MACEs in contemporary population. © 2021 Elsevier HS Journals, Inc.

Recurrence biomarkers of triple negative breast cancer treated with neoadjuvant chemotherapy and anti-EGFR antibodies

To find metastatic recurrence biomarkers of triple-negative breast cancer (TNBC) treated by neoadjuvant chemotherapy and anti-EGFR antibodies (NAT), we evaluated tumor genomic, transcriptomic, and immune features, using MSK-IMPACT assay, gene arrays, Nanostring technology, and TIL assessment on H&E. Six patients experienced a rapid fatal recurrence (RR) and other 6 had later non-fatal recurrences (LR). Before NAT, RR had low expression of 6 MHC class I and 13 MHC class II genes but were enriched in upregulated genes involved in the cell cycle-related pathways. Their TIL number before NAT in RR was very low (<5%) and did not increase after treatment. In post-NAT residual tumors, RR cases showed high expression of SOX2 and CXCR4. Our results indicate that high expression of cell cycle genes, combined with cold immunological phenotype, may predict strong TNBC resistance to NAT and rapid progression after it. This biomarker combination is worth validation in larger studies.

Machine Learning to Predict Outcomes in Patients with Acute Pulmonary Embolism Who Prematurely Discontinued Anticoagulant Therapy.

Patients with pulmonary embolism (PE) who prematurely discontinue anticoagulant therapy (<90 days) are at an increased risk for death or recurrences. We used the data from the RIETE (Registro Informatizado de Pacientes con Enfermedad TromboEmbólica) registry to compare the prognostic ability of five machine-learning (ML) models and logistic regression to identify patients at increased risk for the composite of fatal PE or recurrent venous thromboembolism (VTE) 30 days after discontinuation. ML models included decision tree, k-nearest neighbors algorithm, support vector machine, Ensemble, and neural network [NN]. A "full" model with 70 variables and a "reduced" model with 23 were analyzed. Model performance was assessed by confusion matrix metrics on the testing data for each model and a calibration plot. Among 34,447 patients with PE, 1,348 (3.9%) discontinued therapy prematurely. Fifty-one (3.8%) developed fatal PE or sudden death and 24 (1.8%) had nonfatal VTE recurrences within 30 days after discontinuation. ML-NN was the best method for identification of patients experiencing the composite endpoint, predicting the composite outcome with an area under receiver operating characteristic (ROC) curve of 0.96 (95% confidence interval [CI]: 0.95-0.98), using either 70 or 23 variables captured before discontinuation. Similar numbers were obtained for sensitivity, specificity, positive predictive value, negative predictive value, and accuracy. The discrimination of logistic regression was inferior (area under ROC curve, 0.76 [95% CI: 0.70-0.81]). Calibration plots showed similar deviations from the perfect line for ML-NN and logistic regression. The ML-NN method very well predicted the composite outcome after premature discontinuation of anticoagulation and outperformed traditional logistic regression.

Antiplatelet Therapy after Intracerebral Hemorrhage and Subsequent Clinical Events: A 12-Year South Korean Cohort Study

Introduction: Antiplatelet agents are usually discontinued to reduce hemorrhagic tendency during the acute phase of intracerebral hemorrhage (ICH). However, their use after ICH remains controversial. Methods: This study investigated the effect of antiplatelet agents in ICH survivors. We used the National Health Insurance Service-National Sample Cohort 2002–2013 database for retrospective cohort modeling, estimating the effects of antiplatelet therapy on clinical events. Subgroup analyses assessed antiplatelet medication administered before ICH. Results: The prescription rate of antiplatelets after ICH was also examined. Of 1,007 ICH-surviving patients, 303 subsequent clinical events were recorded, 41 recurrences of nonfatal ICH recurrence, 26 incidents of nonfatal ischemic stroke, 6 nonfatal myocardial infarctions, and 230 incidents of all-cause mortality. The use of antiplatelet therapy significantly decreased the risk of primary outcomes (adjusted hazard ratio [AHR] = 0.743, 95% confidence interval [CI] = 0.578–0.956) and all-cause mortality (AHR = 0.740, 95% CI = 0.552–0.991), especially in patients without a history of antiplatelet treatment. The use of antiplatelet medication after ICH did not significantly increase the recurrence of ICH. The prescription rate of antiplatelet therapy within 1 year was 16.6%. Among 220 patients with a history of using antiplatelet medication, the resumption rate was 0.5% at discharge, 5% after a month, 12.7% after 3 months, and 29.1% after a year. Conclusion: Using antiplatelet treatment after ICH does not increase chances of recurrence, but lowers the occurrence of subsequent clinical events, especially mortality. However, the prescription and resumption rate of antiplatelet therapy after ICH remains low in South Korea.

Abstract 15295: Clinical Characteristics, Treatment Patterns, and Short-term Outcomes in Patients With Isolated Distal Deep Vein Thrombosis

Background: Isolated distal deep vein thrombosis (IDDVT) is a common form of venous thromboembolism (VTE). Limited data exist about the clinical characteristics, initial treatment, and short-term outcomes of these patients. Methods: Using the data from the RIETE registry (05/2001-02/2019), we identified patients with IDDVT without pulmonary embolism (PE). We determined the clinical presentation, initial treatment, and 30-day and 90-day outcomes. We compared the findings with patients with proximal DVT without PE. Results: We identified 5,359 patients with IDDVT (mean age 61±17 years, 50% women). The most prevalent comorbidities were hypertension (39%), anemia (28%), prior VTE (14%), active cancer (12%), heart failure (6.7%), and diabetes (6.6%). Recent surgery was reported in 16%. Most participants received anticoagulation (99%), most commonly with low-molecular-weight heparin (88%). No patient received thrombolytics and use of vena cava filters was rare (0.4%). At 30 days, 59 patients (1.1% [99% CI, 0.8%-1.5%]) died, including only 3 from PE (0.1% [99% CI, 0.01%-0.2%]), 44 (0.8% [99% CI, 0.5%-1.2%]) had nonfatal VTE recurrence, and 31 (0.6% [99% CI, 0.4%-0.9%]) had major bleeding. At 90 days, 2.9% (99% CI, 2.4%-3.6%) died (no additional death from PE), 1.5% (99% CI, 1.1%-2.0%) had nonfatal VTE recurrence, and 0.9% (99% CI, 0.6%-1.3%) had major bleeding. When compared with 25,420 individuals with proximal DVT without PE, those with IDDVT had lower co-morbidity burden including diabetes, heart failure, and cancer, but were more likely to have had recent surgery (P&lt;0.001 for all). Patients with IDDVT also had lower odds of 30-day and 90-day death and major bleeding in bivariate and multivariable analyses (Figure). Conclusions: In a large multinational study, IDDVT occurred in patients with low comorbidity burden. Most patients with IDDVT received anticoagulation. Fatal PE was rare, and patients had a more benign prognosis compared with those with proximal DVT.

Recurrence and mortality 1 year after hospital admission for non-fatal self-harm: a nationwide population-based study.

A large number of people present each day at hospitals for non-fatal deliberate self-harm (DSH). Examination of the short-term risk of non-fatal recurrence and mortality at the national level is of major importance for both individual medical decision-making and global organisation of care. Following the almost exhaustive linkage (96%) of two national registries in France covering 45 million inhabitants (i.e. 70% of the whole population), information about hospitalisation for DSH in 2008-2009 and vital status at 1 year was obtained. Individuals who died during the index hospital stay were excluded from analyses. Over 2 years, 136,451 individuals were hospitalised in medicine or surgery for DSH. The sample comprised 62.8% women, median age 38 in both genders, with two peaks at 16 and 44 years in women, and one peak at 37 years in men. The method used for DSH was drug overdose in 82.1% of cases. Admission to an intensive care unit occurred in 12.9%. Following index hospitalisation, 71.3% returned home and 23.7% were transferred to a psychiatric inpatient care unit. DSH recurrence during the following year occurred in 12.4% of the sample, within the first 6 months in 75.2%, and only once in 74.6%. At 1 year, 2.6% of the sample had died. The overall standardised mortality ratio was 7.5 but reached more than 20 in young adults. The causes were natural causes (35.7%), suicide (34.4%), unspecified cause (17.5%) and accident (12.4%). Most (62.9%) deaths by suicide occurred within the first 6 months following index DSH. Violent means (i.e. not drug overdose) were used in 70% of suicide cases. Concordance between means used for index DSH and for suicide was low (30% overall), except for drug overdose. Main suicide risk factors were older age, being male, use of a violent means at index DSH, index admission to an intensive care unit, a transfer to another medical department or to a psychiatric inpatient unit, and recurrence of DSH. However, these factors had low positive predictive values individually (below 2%). Non-fatal DSH represent frequent events with a significant risk of short-term recurrence and death from various causes. The first 6 months following hospital discharge appear to be a critical period. Specific short-term aftercare programs targeting all people with a DSH episode have to be developed, along other suicide prevention strategies.

The Impacts of Peptic Ulcer on Stroke Recurrence

Peptic ulcer has been associated with an increased risk of stroke. This study aimed to evaluate the impacts of peptic ulcer on stroke recurrence and mortality. Patients with first-ever ischemic stroke were retrospectively confirmed with or without a history of peptic ulcer. The primary end point was defined as fatal and nonfatal stroke recurrence. Risks of 1-year fatal and nonfatal stroke recurrence were analyzed with the Kaplan-Meier method. Predictors of fatal and nonfatal stroke recurrence were evaluated with the Cox proportional hazards model. Among the 2577 enrolled patients with ischemic stroke, 129 (5.0%) had a history of peptic ulcer. The fatal and nonfatal stroke recurrence within 1 year of the index stroke was higher in patients with peptic ulcer than in patients without peptic ulcer (12.4% versus 7.2%, P = .030). Cox proportional hazards model detected that age (hazard ratio [HR] = 1.018, 95% confidence interval [CI] 1.005-1.031, P = .008), hypertension (HR = 1.397, 95% CI 1.017-1.918, P = .039), and history of peptic ulcer (HR = 1.853, 95% CI 1.111-3.091, P = .018) were associated with stroke recurrence. Ischemic stroke patients with peptic ulcer may have an increased risk of stroke recurrence. The results emphasize the importance of appropriate prevention and management of peptic ulcer for secondary stroke prevention.

A prospective validation of the Bova score in normotensive patients with acute pulmonary embolism

BackgroundThe Bova score has shown usefulness in the identification of intermediate-high risk patients with acute pulmonary embolism (PE), but lacks prospective validation.The aim of this study was to prospectively validate the Bova score in different settings from the original derivation cohort. MethodsConsecutive, normotensive patients with acute PE recruited at 13 academic or general hospitals were stratified, using their baseline data, into the three Bova risk stages (I–III). The primary outcome was the 30-day composite of PE-related mortality, hemodynamic collapse and non-fatal PE recurrences in the three risk categories. ResultsIn the study period, 639 patients were enrolled. The primary end point occurred in 45 patients (7.0%; 95% Confidence Intervals, 5.2%–9.3%). Risk stage correlated with the PE-related complication rate (stage I, 2.9%; stage II, 17%; stage III, 27%). Patients classified as stage III by the Bova score had a 6.5-fold increased risk for adverse outcomes (3.1–13.5, p < 0.001) compared with stages I and II combined. Rescue thrombolysis increased from stage I to stage III (0.6%, 12% and 15% respectively). All-cause mortality (5.3%) did not substantially differ among the stages. ConclusionsThe Bova score accurately stratifies normotensive patients with acute PE into stages of increasing risk of 30-day PE-related complications.

Ablation Outcomes and Predictors of Mortality Following Catheter Ablation for Ventricular Tachycardia: Data From the German Multicenter Ablation Registry.

BackgroundVentricular tachycardia (VT) causes significant morbidity and mortality. Implantable cardioverter‐defibrillator shocks terminate VT but confer a significant morbidity and mortality risk. Therefore, VT ablation is increasingly common. Patients with structural heart disease (SHD) and patients with structurally normal hearts as well as the subgroup with and without ischemic heart disease were assessed for predictors of mortality and nonfatal VT recurrence. We present the first multicenter, prospective German VT registry.Methods and ResultsIn 334 patients, 118 structurally normal hearts and 216 SHD (74.5% ischemic heart disease), referred for VT ablation in 38 centers, long‐term follow‐up was assessed for a minimum of 12 months and analyzed for factors predicting VT recurrence rates and mortality. The VTs in SHD patients were more frequently hemodynamically unstable (34.7% versus 12.7%, P<0.0001) or incessant (9.7% versus 2.7%, P<0.05). More SHD patients underwent substrate modification than patients with structurally normal hearts who had more focal ablations. Ablation failure was 9% in both groups. Two‐year mortality was higher in patients with SHD (18.7% versus 3.5%, P<0.001). Predictors of mortality include age >60 years, incessant VT, left ventricular ejection fraction ≤30%, procedural failure, and Class I and III anti‐arrhythmic drug use at discharge. Only procedural failure is a predictor of nonfatal VT recurrence.ConclusionsProcedural failure was the sole independent predictor for nonfatal VT recurrence for our study cohort. This emphasizes the importance of a successful ablation procedure in experienced hands to reduce long‐term mortality and nonfatal VT recurrence.

Abstract 41: Prognostic Value of Perfusion MRI in Patients with Transient Ischemic Attack or Minor Stroke

Background and purpose: We aimed to investigate the role of perfusion MRI parameters (TTP: time to peak, CBF: cerebral blood flow, CBV: cerebral blood volume) as a prognostic factor for the risk of stroke recurrence or cardiovascular outcome in patients with transient ischemic attack (TIA) or minor stroke. Methods: We retrospectively reviewed TIA or minor stroke patients who underwent our stroke MRI protocol (DWI, perfusion MRI, and MRA) in a consecutively collected stroke registry. Primary outcome was nonfatal stroke recurrence and secondary outcome was cardiovascular composite outcome. Multivariate analysis was used to examine the association of perfusion MRI parameters and angiographic findings with the risk of stroke recurrence and cardiovascular event. Results: Of the 326 patients who met inclusion criteria, we identified 15(4.6%) nonfatal strokes and 25(7.7%) cardiovascular composite events during the first 1 year after the index TIA or minor stroke. The presence of regional delayed perfusion on TTP maps (p=0.002) and regional hyperperfusion on CBV maps (p&lt;0.001) were associated with recurrent stroke. In MRA images, concomitant stenosis of the intracranial arteries and/or extracranial carotid arteries was associated with cardiovascular events (p=0.009). Using multivariate cox proportional hazard analysis, presence of regional hyperperfusion on CBV remained an independent predictor of recurrent stroke (HR 10.82, 95% CI 4.19-38.67, p&lt;0.001) and cardiovascular event (HR 6.30, 95% CI 2.67-18.25, p&lt;0.001). The AUC of the CBV maps was also greater than other parameters for the prediction of stroke recurrence (AUC=0.701, 95% CI 0.54-0.86) and cardiovascular composite outcome (AUC=0.628, 95% CI 0.50-0.76). Conclusions: Increased CBV on perfusion MRI, representing the hemodynamic status of postischemic hyperperfusion, could be more useful than other perfusion parameters in predicting poor prognosis of TIA or minor stroke patients.

Predictors of Short- and Long-Term Outcomes of Takotsubo Cardiomyopathy

Takotsubo cardiomyopathy (TC) is a reversible cardiomyopathy with a benign short-term prognosis but is associated with recurrence rate of 10%. Clinical variables that predict long-term mortality and recurrence are unknown; 56 consecutive patients presenting to a single urban medical center who fulfilled the Mayo Clinic criteria for the diagnosis of TC were included. Patients were followed with 100% completeness; >60 clinical factors were analyzed, including presentation, treatment, electrocardiogram, and echocardiographic, angiographic, and demographic variables. Survival analysis was performed using the Kaplan-Meier function and Cox proportional hazards regression models. There were 15 deaths during follow-up: 5 in-hospital, 4 before 90days, and 6 after 90days. Mean survival was 4.47years (95% confidence interval 3.81 to 5.13). All short-term survivors had repeat ejection fraction evaluation demonstrating improvement; 45 of 56 patients were women and 96% were postmenopausal. The nonfatal recurrence rate was 1.8%. QTc interval at presentation was the factor most strongly predictive of overall outcome, after intubation. All patients with mortality had QTc intervals between 400 and 550 ms. In conclusion, this study demonstrates the prognostic significance of QTc prolongation at presentation in TC. Because the cause of TC involves intense catecholamine release and hyperadrenergic tone, the QTc may reflect the individual impact on myocardial repolarization and the balance between sympathetic innervation and parasympathetic compensation. In conclusion, in thisseries, TC was associated with an 8.9% in-hospital mortality, an additional 17.9% mortality after discharge, and a nonfatal recurrence rate of 1.8%. Moreover, the QTc on presentation with TC was predictive of outcome.

Efficacy and safety of growth hormone treatment in adults with growth hormone deficiency: a systematic review of studies on morbidity.

Due to the positive effects demonstrated in randomized clinical trials on cardiovascular surrogate markers and bone metabolism, a positive effect of growth hormone (GH) treatment on clinically relevant end-points seems feasible. In this review, we discuss the long-term efficacy and safety of GH treatment in adult patients with growth hormone deficiency (GHD) with emphasis on morbidity: fatal and nonfatal cardiovascular disease (CVD) and stroke, fractures, fatal and nonfatal malignancies and recurrences, and diabetes mellitus. A positive effect of GH treatment on CVD and fracture risk could be concluded, but study design limitations have to be considered. Stroke and secondary brain tumours remained more prevalent. However, other contributing factors have to be taken into account. Regrowth and recurrences of (peri)pituitary tumours were not increased in patients with GH treatment compared to similar patients without GH treatment. All fatal and nonfatal malignancies were not more prevalent in GH-treated adults compared to the general population. However, follow-up time is still relatively short. The studies on diabetes are difficult to interpret, and more evidence is awaited. In clinical practice, a more individualized assessment seems appropriate, taking into consideration the underlying diagnosis of GHD, other treatment regimens, metabolic profile and the additional beneficial effects of GH set against the possible risks. Large and thoroughly conducted observational studies are needed and seem the only feasible way to inform the ongoing debate on health care costs, drug safety and clinical outcomes.

Radio-frequency ablation as primary management of well-tolerated sustained monomorphic ventricular tachycardia in patients with structural heart disease and left ventricular ejection fraction over 30%

Patients with well-tolerated sustained monomorphic ventricular tachycardia (SMVT) and left ventricular ejection fraction (LVEF) over 30% may benefit from a primary strategy of VT ablation without immediate need for a 'back-up' implantable cardioverter-defibrillator (ICD). One hundred and sixty-six patients with structural heart disease (SHD), LVEF over 30%, and well-tolerated SMVT (no syncope) underwent primary radiofrequency ablation without ICD implantation at eight European centres. There were 139 men (84%) with mean age 62 ± 15 years and mean LVEF of 50 ± 10%. Fifty-five percent had ischaemic heart disease, 19% non-ischaemic cardiomyopathy, and 12% arrhythmogenic right ventricular cardiomyopathy. Three hundred seventy-eight similar patients were implanted with an ICD during the same period and serve as a control group. All-cause mortality was 12% (20 patients) over a mean follow-up of 32 ± 27 months. Eight patients (40%) died from non-cardiovascular causes, 8 (40%) died from non-arrhythmic cardiovascular causes, and 4 (20%) died suddenly (SD) (2.4% of the population). All-cause mortality in the control group was 12%. Twenty-seven patients (16%) had a non-fatal recurrence at a median time of 5 months, while 20 patients (12%) required an ICD, of whom 4 died (20%). Patients with well-tolerated SMVT, SHD, and LVEF > 30% undergoing primary VT ablation without a back-up ICD had a very low rate of arrhythmic death and recurrences were generally non-fatal. These data would support a randomized clinical trial comparing this approach with others incorporating implantation of an ICD as a primary strategy.

Statins after recent stroke reduces recurrence and improves survival in an aging Mediterranean population without known coronary heart disease

The effect of a statin-based medical intervention on prevention of fatal and non-fatal stroke recurrence and the incidence of all-causes mortality have been explored previously in aging populations within the scope of clinical trials research. However, such evidence needs to be explored under conditions of routine clinical practice. The objective of this study was to determine whether statin therapy in patients with a first stroke episode reduces the incidence of 6-year recurrent fatal or non-fatal stroke and all-cause mortality in an aging Mediterranean population without known coronary heart disease followed in routine medical practice. A retrospective study was carried out using records on death, hospitalizations owing to stroke and history of statin therapy included in the Badalona Serveis Assistencials (BSA) database. The cohort studied consisted of consecutive patients covered by the BSA health provider plan with a first-ever acute stroke episode during January 2003 until December 2008, for whom there was available information covering the 6-year follow-up period. Recurrence rate (RR) and incidence rate (IR) of fatal/non-fatal stroke and all-causes mortality were computed. Association with statin therapy was assessed by means of calculation of relative risk (RR) and hazard ratio (HR) using multivariate logistic regression and Cox proportional hazards models controlling for confounding covariates. The cohort comprised a series of 601 consecutive patients [57% men, 75·9 (12·4) years old (88% >60 years)]. Of these, 32% received statins, which were associated with lower fatal/non-fatal recurrent stroke RR; 7% vs. 18% [adjusted RR=0·32 (CI: 0·16-0·61), P=0·001] and lower IR; 16·78 vs. 45·22 events/year-1000 subjects [adjusted HR=0·35 (0·19-0·64), P=0·001]. Similarly, observed all-causes mortality was lower in the cohort receiving statins; 11% vs. 16% [adjusted RR=0·29 (CI: 0·08-1·12), P=0·072], and also mortality rate; 26·09 vs. 36·25 deaths/year-1000 subjects [adjusted HR=0·23 (0·08-0·67), P=0·007]. Statin therapy in patients with first-ever acute stroke lowers the risk of 6-year stroke recurrence and improves survival in an aging Mediterranean cohort. These results add additional evidence in routine clinical practice to the observed effects of statins in clinical trials.

Diagnosis and Management of Isolated Subsegmental Pulmonary Embolism: Review and Assessment of the Options

We assessed the potential safety of withholding treatment of pulmonary embolism (PE) limited to subsegmental branches. Literature review showed that untreated patients with mostly subsegmental PE had no fatal recurrences in 1 to 3 months and no nonfatal recurrences of PE in 3 months. Patients with suspected PE who had nondiagnostic ventilation/perfusion lung scans, adequate cardiorespiratory reserve or low or moderate clinical probability, and negative serial noninvasive leg tests were shown not to require treatment. It appears safe, therefore, to withhold treatment of subsegmental PE providing (1) pulmonary-respiratory reserve is good; (2) no evidence of deep venous thrombosis (DVT) on serial testing; (3) major risk factor for PE was transient and no longer present; (4) no history of central venous catheterization or atrial fibrillation; and (5) willingness to return for serial venous ultrasound. After fully informing patients, some may choose to be treated and some may choose not to be treated.

Stroke prevention: might vitamin D be safer than statins?

Drs. Paliani and Ricci [1] recommend statin therapy in both primary and secondary prevention of stroke. However, although statin treatment might be effective in the prevention of stroke in patients with known coronary-artery disease but without a history of cerebrovascular disease, its role in the secondary prevention of stroke raises some serious concerns [2]. Indeed, a closer look at the results of the Stroke Prevention with Aggressive Reduction in Cholesterol (SPARCL) trial [3], the only study specifically designed to investigate the role of high-dose statin therapy in the secondary prevention of stroke, should question the safety of statin therapy in patients with a history of cerebrovascular disease. The well publicized effect of highdose statin on stroke recurrences in the SPARCL trial reaches significance only with the merging of fatal and nonfatal outcomes. In fact, as compared with placebo, the use of high-dose atorvastatin in accurately selected patients who had a stroke or TIA is associated with a nonsignificant 13% risk reduction of nonfatal stroke during a 5-year follow-up, without improving overall survival (five more deaths in the statin arm), and with 66% increase in the relative risk of hemorrhagic stroke among the patients receiving the statin drug. The latter outcome is neither unlikely a chance finding, nor it could be related to the fact that the SPARCL study not only included patients with ischemic stroke as an entry event, but also patients with hemorrhagic stroke. A sensitivity analysis excluding all patients with a hemorrhagic stroke as an entry event in the SPARCL trial finds that statin treatment is still associated with an increased risk of hemorrhagic stroke [4]. In a subgroup of patients with a history of cerebrovascular disease enrolled in the Heart Protection Study, which did not include patients with hemorrhagic stroke, a similar increased risk of hemorrhagic stroke during follow-up is demonstrated [4]. Furthermore, in the same SPARCL trial, high-dose atorvastatin fails to significantly reduce nonfatal stroke recurrences in every subgroup of studied patients [2], such as men and women, individuals older than 65 years, and patients with and without carotid stenosis. Of concern, despite in the trial design, among the primary efficacy parameters, it was reported that every effort should have been made to determine whether strokes were ischemic or hemorrhagic [3], this worrisome statin side-effect was never reported in any secondary analysis [2]. Finally, Drs. Paliani and Ricci [1] highlight that in combination with other preventive strategies, such as blood pressure-lowering and antithrombotic treatment, in the prevention of stroke, we should also focus on lipid-lowering therapies, beyond statins. However, this approach may distract from other safer tools for the prevention and treatment of stroke. In this setting, an emerging role is related to the vitamin D status. Mounting evidence suggests that vitamin D deficiency is associated with an increased risk of stroke [5]. This notion is supported by studies showing that several risk factors for cerebrovascular events are associated with low 25-hydroxyvitamin D levels L. Mascitelli (&) Comando Brigata Alpina ‘‘Julia’’, Medical Service, 8 Via S. Agostino, 33100 Udine, Italy e-mail: lumasci@libero.it