3D Printing Direct Powder Extrusion in the Production of Drug Delivery Systems: State of the Art and Future Perspectives.

The production of tailored, on-demand drug delivery systems has gained attention in pharmaceutical development over the last few years, thanks to the application of 3D printing technology in the pharmaceutical field. Recently, direct powder extrusion (DPE) has emerged among the extrusion-based additive manufacturing techniques. It is a one-step procedure that allows the direct processing of powdered formulations. The aim of this systematic literature review is to analyze the production of drug delivery systems using DPE. A total of 27 articles have been identified through scientific databases (Scopus, PubMed, and ScienceDirect). The main characteristics of the three types of 3D printers based on DPE have been discussed. The selection of polymers and auxiliary excipients, as well as the flowability of the powder mixture, the rheological properties of the molten material, and the printing temperatures have been identified as the main critical parameters for successful printing. A wide range of drug delivery systems with varied geometries and different drug release profiles intended for oral, buccal, parenteral, and transdermal routes have been produced. The ability of this technique to manufacture personalized, on-demand drug delivery systems has been proven. For all these reasons, its implementation in hospital settings in the near future seems promising.

Extrusion-based technologies for 3D printing: a comparative study of the processability of thermoplastic polyurethane-based formulations.

Thermoplastic polyurethanes (TPU) offer excellent properties for a wide range of dosage forms. These polymers have been successfully utilized in personalized medicine production using fused deposition modeling (FDM) 3D printing (3DP). However, direct powder extrusion (DPE) has been introduced recently as a challenging technique since it eliminates filament production before 3DP, reducing thermal stress, production time, and costs. This study compares DPE and single-screw extrusion for binary (drug-TPU) and ternary (drug-TPU-magnesium stearate [MS]) mixtures containing from 20 to 60% w/w of theophylline. Powder flow, mechanical properties, fractal analysis, and percolation theory were utilized to analyze critical properties of the extrudates. All the mixtures could be processed at a temperature range between 130 and 160 °C. Extrudates containing up to 50% w/w of drug (up to 30% w/w of drug in the case of single-screw extrusion binary filaments) showed toughness values above the critical threshold of 80 kg/mm2. MS improved flow in mixtures where the drug is the only percolating component, reduced until 25 °C the DPE temperature and decreased the extrudate roughness in high drug content systems. The potential of DPE as an efficient one-step additive manufacturing technique in healthcare environments to produce TPU-based tailored on-demand medicines has been demonstrated.

Long-term prognostic impact of beta-blockers in patients with Takotsubo syndrome: Results from the RETAKO Registry.

BACKGROUND: No evidence-based therapy has yet been established for Takotsubo syndrome (TTS). Given the putative harmful effects of catecholamines in patients with TTS, beta-blockers may potentially decrease the intensity of the detrimental cardiac effects in those patients. OBJECTIVE: The purpose of this study was to assess the impact of beta-blocker therapy on long-term mortality and TTS recurrence. METHODS: The cohort study used the national Spanish Registry on TakoTsubo Syndrome (RETAKO). A total of 970 TTS post-discharge survivors, without pheochromocytoma, left ventricular outflow tract obstruction, sustained ventricular arrhythmias, and significant bradyarrhythmias, between January 1, 2003, and July 31, 2018, were assessed. Cox regression analysis and inverse probability weighting (IPW) propensity score analysis were used to evaluate the association between beta-blocker therapy and survival free of TTS recurrence. RESULTS: From 970 TTS patients, 582 (60.0%) received beta-blockers. During a mean follow-up of 2.5±3.3 years, there were 87 deaths (3.6 per 100 patients/year) and 29 TTS recurrences (1.2 per 100 patient/year). There was no significant difference in follow-up mortality or TTS recurrence in unadjusted and adjusted Cox analysis (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.59-1.27, and 0.95, 95% CI 0.57-1.13, respectively). After weighting and adjusting by IPW, differences in one-year survival free of TTS recurrence between patients treated and untreated with beta-blockers were not found (average treatment effect -0.01, 95% CI -0.07 to 0.04; p=0.621). CONCLUSIONS: In this observational nationwide study from Spain, there was no significant association between beta-blocker therapy and follow-up survival free of TTS recurrence.

3D Printed Fractal-like Structures with High Percentage of Drug for Zero-Order Colonic Release.

Colonic drug delivery of drugs is an area of great interest due to the need to treat high prevalence colonic local diseases as well as systemic conditions that may benefit from the advantages associated to this route of drug administration. In the last decade, the use of 3D printing technologies has expanded, offering the possibility of preparing personalized medicines in small batches directly at the point of care. The aim of this work is to design a high drug loaded 3D printed system prepared by a combination of Fused Deposition Modelling (FDM) and Injection Volume Filling (IVF) techniques intended for zero-order colonic drug release. For this purpose, different batches of binary and ternary filaments based on the thermoplastic polyurethane Tecoflex EG-72D (TPU), theophylline anhydrous (AT) as model drug, and magnesium stearate as lubricant have been developed and characterized. Filaments with the highest drug load and the best rheological properties were selected for the manufacture of a printed fractal-like structure based on multiple toroids. This design was proposed to provide high surface area, leading to increased drug release and water uptake in the colonic region. This structure was 3D printed by FDM and then coated in a unique step by IVF technology using the enteric polymer DrugCoat S 12.5. This way, an additional coating process is avoided, reducing costs and production time. Studies of drug release confirmed the ability of the structures to provide a five-hour period of constant drug delivery in the colonic region.

Instantaneous Wave-Free Ratio for the Assessment of Intermediate Left Main Coronary Artery Stenosis: Correlations With Fractional Flow Reserve/Intravascular Ultrasound and Prognostic Implications: The iLITRO-EPIC07 Study.

BACKGROUND: There is little information available on agreement between fractional flow reserve (FFR) and instantaneous wave-free ratio (iFR) in left main coronary artery (LMCA) intermediate stenosis. Besides, several meta-analyses support the use of FFR to guide LMCA revascularization, but limited information is available on iFR in this setting. Our aims were to establish the concordance between FFR and iFR in intermediate LMCA lesions, to evaluate with intravascular ultrasound (IVUS) in cases of FFR/iFR discordance, and to prospectively validate the safety of deferring revascularization based on a hybrid decision-making strategy combining iFR and IVUS. METHODS: Prospective, observational, multicenter registry with 300 consecutive patients with intermediate LMCA stenosis who underwent FFR and iFR and, in case of discordance, IVUS and minimal lumen area measurements. Primary clinical end point was a composite of cardiovascular death, LMCA lesion-related nonfatal myocardial infarction, or unplanned LMCA revascularization. RESULTS: FFR and iFR had an agreement of 80% (both positive in 67 and both negative in 167 patients); in case of disagreement (31 FFR+/iFR- and 29 FFR-/iFR+) minimal lumen area was ≥6 mm2 in 8.7% of patients with FFR+ and 14.6% with iFR+. Among the 300 patients, 105 (35%) underwent revascularization and 181 (60%) were deferred according to iFR and IVUS. At a median follow-up of 20 months, major adverse cardiac events incidence was 8.3% in the defer group and 13.3% in the revascularization group (hazard ratio, 0.71 [95% CI 0.30-1.72]; P=0.45). CONCLUSIONS: In patients with intermediate LMCA stenosis, a physiology-guided treatment decision is feasible either with FFR or iFR with moderate concordance between both indices. In case of disagreement, the use of IVUS may be useful to indicate revascularization. Deferral of revascularization based on iFR appears to be safe in terms of major adverse cardiac events. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03767621.

Transjugular closure of a residual septal device defect: a case report.

Background: Severe residual shunts after percutaneous closure of atrial septal defects are unusual. These patients are usually considered candidates for surgery. Case summary: We describe the transjugular closure of a residual atrial septal defect with significant left-to-right shunt due to a malpositioned large atrial septal device in a symptomatic 74-year-old female. Transjugular access was chosen first due to the unfavourable position of the device for delivery of a new one from the femoral approach. An overlapping Figulla® Flex II 27/30 mm PFO device was successfully implanted with the guidance of 3D-transoesophageal echocardiography. Discussion: This case demonstrates the safety and feasibility of transjugular access as an alternative to femoral or transhepatic approaches in patients with difficult atrial septal anatomies, who are usually referred for surgery.

Prospective application of a bleeding and ischemic risks-adjusted antithrombotic protocol in elderly patients revascularized with everolimus-eluting stents: EPIC05-Sierra75 study.

OBJECTIVES: Elderly patients show a higher incidence of ischemic and bleeding events after percutaneous transluminal coronary intervention (PCI). We sought to investigate outcomes in elderly patients treated with antithrombotic strategy guided by bleeding and ischemic risks after revascularization with last generation everolimus-eluting stent (EES). METHODS: Prospective multicenter registry including patients over 75 years revascularized with EES and antithrombotic therapy guided by clinical presentation, PCI complexity and PRECISE DAPT score. Co-primary safety endpoints were: (1) composite of cardiac death, myocardial infarction and stent thrombosis and; (2) bleeding (BARC 2-5). Primary efficacy endpoint was target lesion revascularization. A matched group of patients revascularized with current drug-eluting stents and no such tailored antithrombotic therapy was used as control. RESULTS: Finally, 1064 patients were included in SIERRA-75 cohort, 80.8 ± 4.2 years, 36.6% women, 71% acute coronary syndromes (ACS) and 53.6% complex PCI. Co-primary safety endpoint of major adverse cardiovascular events was met in 6.2%, co-primary safety endpoint of bleeding in 7.8% and primary efficacy endpoint of TKLR in 1.5%. The multivariable adjusted model showed no significant association of the prescribed short/long dual antiplatelet therapy (DAPT) durations with any endpoint suggesting a well tailored therapy. No stent thrombosis reported in the subgroup with 1-3 months DAPT duration. As compared to control group, bleeding BARC 2-5 was significantly lower in SIERRA-75 group (7.4% vs. 10.2%, P = 0.04) as well as the net safety-efficacy endpoint (14.3% vs. 18.5%, P = 0.02). CONCLUSIONS: In elderly population, the application of this risks-adjusted antithrombotic protocol after revascularization with last generation EES seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes.

Assessment of the Extrusion Process and Printability of Suspension-Type Drug-Loaded AffinisolTM Filaments for 3D Printing.

Three-dimensional (3D) printing technology enables the design of new drug delivery systems for personalised medicine. Polymers that can be molten are needed to obtain extruded filaments for Fused Deposition Modelling (FDM), one of the most frequently employed techniques for 3D printing. The aim of this work was to evaluate the extrusion process and the physical appearance of filaments made of a hydrophilic polymer and a non-molten model drug. Metformin was used as model drug and Affinisol™ 15LV as the main carrier. Drug-loaded filaments were obtained by using a single-screw extruder and, subsequently, their printability was tested. Blends containing up to a 60% and 50% drug load with 5% and 7.5% of auxiliary excipients, respectively, were successfully extruded. Between the obtained filaments, those containing up to 50% of the drug were suitable for use in FDM 3D printing. The studied parameters, including residence time, flow speed, brittleness, and fractal dimension, reflect a critical point in the extrusion process at between 30-40% drug load. This finding could be essential for understanding the behaviour of filaments containing a non-molten component.

Efficacy and safety of abciximab versus tirofiban in addition to ticagrelor in STEMI patients undergoing primary percutaneous intervention.

Platelet glycoprotein IIb/IIIa inhibitors (GPIs) have been part of the adjuvant treatment of acute coronary syndrome for years. However, real-life data regarding the efficacy and safety of GPIs under the current indications are lacking in the setting of potent platelet inhibition. The objectives were to assess the efficacy and safety of abciximab versus tirofiban in patients with ST-elevation acute myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) and pretreated with ticagrelor, and to identify independent predictor factors of efficacy, bleeding and platelet drop. Three hundred sixty-two patients were divided by GPI administered. Clinical, laboratory, angiographic and outcome characteristics were compared. The primary objective was a composite efficacy endpoint (death from any cause, nonfatal myocardial infarction and nonfatal stroke) at 30 days. The secondary objectives were its individual components, safety (bleeding) and the impact on platelet count during hospital stay. The composite efficacy endpoint was similar in the abciximab and tirofiban groups (6.1% vs 7.3%; p = .632). There were also no differences in cardiovascular death (2.5% vs 2.4%; p = .958), nonfatal myocardial infarction (3% vs 4.3%; p = .521) and nonfatal stroke (0.5% vs 1.8%; p = .332). Tirofiban administration was associated with a higher incidence of bleeding (11.6% vs 22%; p = .008) with no differences in BARC ≥ 3b bleeding (3.6 vs 2.5%; p = .760). In STEMI patients undergoing PPCI with ticagrelor, abciximab and tirofiban had similar rates in the composite efficacy endpoint at 30 days. The 30-day bleeding rate was significantly higher in the tirofiban group. Tirofiban administration was an independent predictor of both bleeding and platelet count drop.

3D printed systems for colon-specific delivery of camptothecin-loaded chitosan micelles.

The use of 3D printing technology in the manufacturing of drug delivery systems has expanded and benefit of a customized care. The ability to create tailor-made structures filled with drugs/delivery systems with suitable drug dosage is especially appealing in the field of nanomedicine. In this work, chitosan-based polymeric micelles loaded with camptothecin (CPT) were incorporated into 3D printing systems (printfills) sealed with an enteric layer, aiming to protect the nanosystems from the harsh environment of the gastrointestinal tract (GIT). Polymeric micelles and printfills were fully characterized and, a simulated digestion of the 3D systems upon an oral administration was performed. The printfills maintained intact at the simulated gastric pH of the stomach and, only released the micelles at the colonic pH. From there, the dissolution media was used to recreate the intestinal absorption and, chitosan micelles showed a significant increase of the CPT permeability compared to the free drug, reaching an apparent permeability coefficient (Papp) of around 9×10-6 cm/s in a 3D intestinal cell-based model. The combination of 3D printing with nanotechnology appears to have great potential for the colon-specific release of polymeric micelles, thereby increasing intestinal absorption while protecting the system/drug from degradation throughout the GIT.

Triflusal in Patients with Acute Coronary Syndrome and Acetylsalicylic Acid Hypersensitivity.

BACKGROUND: Acetylsalicylic acid hypersensitivity (ASAH) limits therapeutic options in patients with acute coronary syndrome (ACS), who benefit from dual antiplatelet therapy (DAPT), especially when undergoing stent implantation. Our aim was to evaluate the safety and efficacy of triflusal in patients with ACS and ASAH. METHODS AND RESULTS: Two-center retrospective study of patients diagnosed with ACS and ASAH from January 1, 2000, to May 1, 2020. Sixty-six patients were treated with triflusal. ASAH was confirmed with tests in 15 patients (22.7%). Forty-nine patients (74.2%) presented history of other drug allergies. Fifty-nine patients (89.4%) underwent stent implantation. DAPT was prescribed for ≥12 months in 54 patients. No adverse reactions to triflusal were reported. During a median follow-up of 5.12 years [IQR 2.7-9.9], rate of cardiovascular (CV) mortality was 6.1%, nonfatal myocardial infarction 12.1%, and ischemic stroke 4.5%. No cases of definite stent thrombosis occurred. Bleeding Academic Research Consortium grade ≥2 was observed in 3 patients during follow-up. CONCLUSION: In this series of patients presenting with ACS and ASA hypersensitivity, triflusal showed good tolerability and was associated with a low rate of CV and bleeding events.

High-degree atrioventricular block. An unusual presentation of Takotsubo cardiomyopathy: a case report.

BACKGROUND: Takotsubo cardiomyopathy is a non-ischemic cardiomyopathy characterized by acute left ventricular systolic dysfunction with transient wall motion abnormalities without a culprit coronary stenosis or other concurrent diagnoses. Its coexistence with transient high-degree AV block is very infrequent. CASE PRESENTATION: A 61-year-old man presented with a new onset of high degree AV block without ST segment deviations developing an anterior and apical dyskinesia with a low left ventricular ejection fraction in the absence of coronary artery disease. CONCLUSION: Atrioventricular block is an uncommon presentation of Takotsubo syndrome. The management of patients with relevant conduction disorders in this scenario is a challenge for the clinician. In case of persistence of advanced conduction disorders, it seems appropriate to implant a pacemaker.

3D Printed Drug Delivery Systems Based on Natural Products.

In the last few years, the employment of 3D printing technologies in the manufacture of drug delivery systems has increased, due to the advantages that they offer for personalized medicine. Thus, the possibility of producing sophisticated and tailor-made structures loaded with drugs intended for tissue engineering and optimizing the drug dose is particularly interesting in the case of pediatric and geriatric population. Natural products provide a wide range of advantages for their application as pharmaceutical excipients, as well as in scaffolds purposed for tissue engineering prepared by 3D printing technologies. The ability of biopolymers to form hydrogels is exploited in pressure assisted microsyringe and inkjet techniques, resulting in suitable porous matrices for the printing of living cells, as well as thermolabile drugs. In this review, we analyze the 3D printing technologies employed for the preparation of drug delivery systems based on natural products. Moreover, the 3D printed drug delivery systems containing natural products are described, highlighting the advantages offered by these types of excipients.

Short- and Long-Term Prognosis of Patients With Takotsubo Syndrome Based on Different Triggers: Importance of the Physical Nature.

Background Takotsubo syndrome (TTS) is an acute reversible heart condition initially believed to represent a benign pathology attributable to its self-limiting clinical course; however, little is known about its prognosis based on different triggers. This study compared short- and long-term outcomes between TTS based on different triggers, focusing on various physical triggering events. Methods and Results We analyzed patients with a definitive TTS diagnosis recruited for the Spanish National Registry on TTS (RETAKO [Registry on Takotsubo Syndrome]). Short- and long-term outcomes were compared between different groups according to triggering factors. A total of 939 patients were included. An emotional trigger was detected in 340 patients (36.2%), a physical trigger in 293 patients (31.2%), and none could be identified in 306 patients (32.6%). The main physical triggers observed were infections (30.7%), followed by surgical procedures (22.5%), physical activities (18.4%), episodes of severe hypoxia (18.4%), and neurological events (9.9%). TTS triggered by physical factors showed higher mortality in the short and long term, and within this group, patients whose physical trigger was hypoxia were those who had a worse prognosis, in addition to being triggered by physical factors, including age >70 years, diabetes mellitus, left ventricular eyection fraction <30% and shock on admission, and increased long-term mortality risk. Conclusions TTS triggered by physical factors could present a worse prognosis in terms of mortality. Under the TTS label, there could be as yet undiscovered very different clinical profiles, whose differentiation could lead to individual better management, and therefore the perception of TTS as having a benign prognosis should be generally ruled out.

Printfills: 3D printed systems combining fused deposition modeling and injection volume filling. Application to colon-specific drug delivery.

Three-dimensional printing has become a feasible manufacturing technique for pharmaceutical products providing cheap and accurate freeform systems with a great potential for personalized-dose drugs. Fused Deposition Modeling (FDM) highlights among other 3D technologies due to its low cost and easy to operate but, until now, it has the drawbacks of the low drug loaded and the impossibility to print thermosensitive drugs. So, intermediate processes such as hot melt extrusion are frequently associated with FDM. Here, pharmaceutical dosage forms have been manufactured for the first time with a 3D printer combining two different printing technologies: FDM and injection volume filling (IVF), performing customized extruded scaffolds in which a liquid or semisolid system can be injected at room temperature. A model drug and a pH-sensitive polymer were successfully incorporated during the construction of the extruded backbone of the systems, called printfills (printed systems filled with a liquid or semisolid). SEM microphotographs of printfills show the sealing of the structure in the perimeter and the homogeneity of the colonic film formed in the upper side. Thus, the addition of the pH-sensitive polymer does not need an additional process in a fluidized bed or coating pan. Results from drug release studies performed at different pH confirm the ability of printfills for colon-specific drug delivery. Therefore, IVF technology complements FDM, solving its main limitations providing an easy, automatized and versatile technology to manufacture tailored drug delivery platforms, avoiding other intermediate processes.

Short- and Long-Term Prognostic Relevance of Cardiogenic Shock in Takotsubo Syndrome: Results From the RETAKO Registry.

OBJECTIVES: This study sought to describe the incidence, determinants, and prognostic impact of cardiogenic shock (CS) in takotsubo syndrome (TTS). BACKGROUND: TTS can be associated with severe hemodynamic instability. The prognostic implication of CS has not been well characterized in large studies of TTS. METHODS: We analyzed patients with a definitive TTS diagnosis (modified Mayo criteria) who were recruited for the National RETAKO (Registry on Takotsubo Syndrome) trial from 2003 to 2016. Cox and competing risk regression models were used to identify factors associated with mortality and recurrences. RESULTS: A total of 711 patients were included, 81 (11.4%) of whom developed CS. Male sex, QTc interval prolongation, lower left ventricular ejection fraction at admission, physical triggers, and presence of "a significant" left intraventricular pressure gradient, were associated with CS (C index = 0.85). In-hospital complication rates, including mortality, were significantly higher in patients with CS. Over a median follow-up of 284 days (interquartile range: 94 to 929 days), CS was the strongest independent predictor of long-term, all-cause mortality (hazard ratio [HR]: 5.38; 95% confidence interval [CI]: 2.60 to 8.38); cardiovascular (CV) death (sub-HR: 4.29; 95% CI: 2.40 to 21.2), and non-CV death (sub-HR: 3.34; 95% CI: 1.70 to 6.53), whereas no significant difference in the recurrence rate was observed between groups (sub-HR: 0.76; 95% CI: 0.10 to 5.95). Among patients with CS, those who received beta-blockers at hospital discharge experienced lower 1-year mortality compared with those who did not receive a beta-blocker (HR: 0.52; 95% CI: 0.44 to 0.79; pinteraction = 0.043). CONCLUSIONS: CS is not uncommon and is associated with worse short- and long-term prognosis in TTS. CS complicating TTS may constitute a marker of underlying disease severity and could identify a masked heart failure phenotype with increased vulnerability to catecholamine-mediated myocardial stunning.

Síndrome de tako-tsubo en varones: infrecuente, pero con mal pronóstico / Tako-tsubo syndrome in men: rare, but with poor prognosis

Introducción y objetivos: El síndrome de tako-tsubo es un proceso patológico potencialmente grave durante la fase aguda. Simula un infarto de miocardio, sin que haya lesiones coronarias potencialmente responsables. El objetivo de este trabajo es analizar la evolución y el pronóstico de los pacientes con síndrome de tako-tsubo en función del sexo. Métodos: Se analizaron las características de los pacientes incluidos en el registro RETAKO durante los años 2003 a 2015, un registro multicéntrico en el que participaron 32 hospitales españoles. Resultados: De los 562 pacientes incluidos, 493 (87,7%) eran mujeres. El dolor torácico fue menos frecuente como síntoma inicial en los varones que en las mujeres (43 [66,2%] frente a 390 [82,8%]; p < 0,01). El pronóstico fue peor en los varones, con mayor mortalidad intrahospitalaria (3 [4,4%] frente a 1 [0,2%]; p < 0,01), duración más prolongada de ingreso en cuidados intensivos (4,2 ± 3,7 frente a 3,2 ± 3,2 días; p = 0,03) y mayor frecuencia de insuficiencia cardiaca grave (22 [33,3%] frente a 95 [20,3%]; p = 0,02). Sin embargo la aparición de obstrucción dinámica a nivel del tracto de salida del ventrículo izquierdo se observó exclusivamente en mujeres (39 [7,9%] frente a 0 [0,0%]; p = 0,02) y la incidencia de insuficiencia mitral funcional también fue mayor en ellas (52 [10,6%] frente a 2 [2,9%]; p = 0,04). Conclusiones: El síndrome de tako-tsubo es una enfermedad que muestra grandes diferencias en función del sexo en cuanto a su incidencia, presentación y evolución, con un peor pronóstico en los varones

Introduction and objectives: Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. Methods: We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. Results: Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). Conclusions: Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men

Tako-tsubo Syndrome in Men: Rare, but With Poor Prognosis.

INTRODUCTION AND OBJECTIVES: Tako-tsubo syndrome is a potentially serious disease during the acute phase. It mimics myocardial infarction, but with no potentially causative coronary lesions. The aim of this study was to analyze the clinical course and outcome of patients with tako-tsubo syndrome by sex. METHODS: We analyzed the characteristics of patients included in the RETAKO registry from 2003 to 2015, a multicenter registry with participation of 32 Spanish hospitals. RESULTS: Of 562 patients included, 493 (87.7%) were women. Chest pain was less frequent as an initial symptom in men than in women (43 [66.2%] vs 390 [82.8%]; P < .01). The prognosis was worse in men, with higher in-hospital mortality (3 [4.4%] vs 1 [0.2%]; P < .01), longer intensive care stay (4.2 ± 3.7 vs 3.2 ± 3.2 days; P = .03) and a higher frequency of severe heart failure (22 [33.3%] vs 95 [20.3%]; P = .02). However, dynamic obstruction at the left-ventricular outflow tract occurred exclusively in women (39 [7.9%] vs 0 [0.0%]; P = .02). The incidence of functional mitral regurgitation was also higher in women (52 [10.6%] vs 2 [2.9%]; P = .04). CONCLUSIONS: Tako-tsubo syndrome shows wide differences by sex in terms of its incidence, presentation, and outcomes. Prognosis is worse in men.