Timing of P2Y12 Inhibitor Administration in Patients With STEMI Undergoing Primary PCI.

BACKGROUND: The optimal timing of P2Y12 inhibitor administration in patients with ST-segment elevation myocardial infarction (STEMI) has not been completely elucidating. OBJECTIVES: This analysis from a prospective multicenter registry sought to assess the safety and effectiveness of P2Y12 inhibitor pretreatment in patients transferred for primary percutaneous coronary intervention (PCI) within a regional STEMI network. METHODS: Pretreatment was defined as P2Y12 inhibitor administration before coronary angiography. Endpoints were major adverse cardiac events (MACE), major bleeding, and net adverse clinical events, a composite of MACE or major bleeding, within 30 days of index admission. Association of P2Y12 inhibitor pretreatment with outcomes was modeled using doubly robust weighted estimators based on propensity score analysis. RESULTS: Of 1,624 patients included, 1,033 received P2Y12 inhibitors before angiography and 591 in the catheterization laboratory (cath lab). The non-pretreated cohort more often had history of coronary artery disease and were more likely to receive antiplatelet therapy before the index admission. After adjustment for confounding and dependent censoring, pretreatment with P2Y12 inhibitors predicted lower risk of MACE (adjusted HR: 0.53; 95% CI: 0.37-0.76), without increasing bleeding risk (adjusted HR: 0.62; 95% CI: 0.36-1.05), resulting in superior net clinical benefit (adjusted HR: 0.47; 95% CI: 0.26-0.86) compared with in-cath lab administration of P2Y12 inhibitors. There was a significant treatment-by-time interaction for MACE risk, whereby the observed benefits of pretreatment only became apparent when time between P2Y12 inhibitor administration and PCI was longer than 80 minutes. CONCLUSIONS: In contemporary patients with STEMI transferred for primary PCI, pretreatment with P2Y12 inhibitors was associated with a significant time-dependent reduction of 30-day MACE without increasing bleeding risk.

Trigger-Associated Clinical Implications and Outcomes in Takotsubo Syndrome: Results From the Multicenter GEIST Registry.

Background Takotsubo syndrome is usually triggered by a stressful event. The type of trigger seems to influence the outcome and should therefore be considered separately. Methods and Results Patients included in the GEIST (German-Italian-Spanish Takotsubo) registry were categorized according to physical trigger (PT), emotional trigger (ET), and no trigger (NT) of Takotsubo syndrome. Clinical characteristics as well as outcome predictors were analyzed. Overall, 2482 patients were included. ET was detected in 910 patients (36.7%), PT in 885 patients (34.4%), and NT was observed in 717 patients (28.9%). Compared with patients with PT or NT, patients with ET were younger, less frequently men, and had a lower prevalence of comorbidities. Adverse in-hospital events (NT: 18.8% versus PT: 27.1% versus ET: 12.1%, P<0.001) and long-term mortality rates (NT: 14.4% versus PT: 21.6% versus ET: 8.5%, P<0.001) were significantly lower in patients with ET. Increasing age (P<0.001), male sex (P=0.007), diabetes (P<0.001), malignancy (P=0.002), and a neurological disorder (P<0.001) were associated with a higher risk of long-term mortality, while chest pain (P=0.035) and treatment with angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (P=0.027) were confirmed as independent predictors for a lower risk of long-term mortality. Conclusions Patients with ET have better clinical conditions and a lower mortality rate. Increasing age, male sex, malignancy, a neurological disorder, chest pain, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and diabetes were confirmed as predictors of long-term mortality.

[Heart rate disorders in patients with Tako-tsubo syndrome]. / Trastornos del ritmo cardiaco en pacientes con síndrome de Tako-tsubo.

OBJECTIVES: This study sought to evaluate the incidence, prognosis and treatment of heart rhythm disorders (HRD) in Tako-tsubo syndrome (TTS). BACKGROUND: TTS is associated with HRD. The HRD prognostic value is not well characterized in TTS yet. METHODS: The HRD of patients included in the National Registry of Tako-tsubo syndrome, admitted between 2002 and 2018 and coming from 38 hospitals throughout the country, was analyzed. We analyzed any heart rhythm disorder in patients presented before admission, at admission and in long-term follow-up. RESULTS: All types of HRD were described in 259 (23.5%) cases, from a cohort of 1,097 consecutive patients with TTS. HRD was more associated with diabetes mellitus, smoking, hyperuricemia, sleep apnea, anemia with a worse LVEF on admission. The most frequent HRD was a new onset of atrial fibrillation. During hospitalization, patients with HRD showed more complications such as shock on admission, major bleeding, acute renal failure, and combined infections. At follow-up, they presented higher mortality and more major adverse cardiac events, but with a non-significant correlation. CONCLUSIONS: The incidence of HRD in patients with TTS is not infrequent. TTS, when associated with HRD, presents more complications and a worse prognosis both in hospital and in the long term.

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.

Gender Differences in Takotsubo Syndrome.

BACKGROUND: Male sex in takotsubo syndrome (TTS) has a low incidence and it is still not well characterized. OBJECTIVES: The aim of the present study is to describe TTS sex differences. METHODS: TTS patients enrolled in the international multicenter GEIST (GErman Italian Spanish Takotsubo) registry were analyzed. Comparisons between sexes were performed within the overall cohort and using an adjusted analysis with 1:1 propensity score matching for age, comorbidities, and kind of trigger. RESULTS: In total, 286 (11%) of 2,492 TTS patients were men. Male patients were younger (age 69 ± 13 years vs 71 ± 11 years; P = 0.005), with higher prevalence of comorbid conditions (diabetes mellitus 25% vs 19%; P = 0.01; pulmonary diseases 21% vs 15%; P = 0.006; malignancies 25% vs 13%; P < 0.001) and physical trigger (55 vs 32% P < 0.01). Propensity-score matching yielded 207 patients from each group. After 1:1 propensity matching, male patients had higher rates of cardiogenic shock and in-hospital mortality (16% vs 6% and 8% vs 3%, respectively; both P < 0.05). Long-term mortality rate was 4.3% per patient-year (men 10%, women 3.8%). Survival analysis showed higher mortality rate in men during the acute phase in both cohorts (overall: P < 0.001; matched: P = 0.001); mortality rate after 60 days was higher in men in the overall (P = 0.002) but not in the matched cohort (P = 0.541). Within the overall population, male sex remained independently associated with both in-hospital (OR: 2.26; 95% CI: 1.16-4.40) and long-term mortality (HR: 1.83; 95% CI: 1.32-2.52). CONCLUSIONS: Male TTS is featured by a distinct high-risk phenotype requiring close in-hospital monitoring and long-term follow-up.

Takotsubo syndrome and cancer, clinical and prognostic implications, insights of RETAKO. / Implicaciones clínicas y pronósticas en síndrome de Takotsubo y cáncer: percepciones del registro RETAKO.

BACKGROUND AND OBJECTIVES: A relationship between neoplasms and Takotsubo syndrome (TS) has been postulated. Our goal was to determine its prevalence in patients with TS, compare the clinical profile of TS with or without cancer and study its long-term evolution. MATERIALS AND METHODS: The oncological situation of patients included in the National Registry on TAKOtsubo syndrome (RETAKO), admitted between 2002 and 2019, provided by 38 hospitals throughout the country is analysed. Any history of malignancy or tumour, even benign, that received chemotherapy, radiotherapy or specific surgery, current or past, was considered. RESULTS: Any type of neoplasm was described in 129 (11.8%), within a cohort of 1,097 patients with TS. The cohort of patients with neoplasm, with a lower percentage of women (79.1 vs. 88.3%; P=.003), showed a non-significant tendency at an older age, hyperuricaemia, sleep apnoea and lower LVEF on admission, with a similar cardiovascular risk factor profile, but more chronic anaemia and immunosuppression. The most common neoplasm was breast cancer. During their hospital stay, the cancer patients suffered more complications, highlighting heart failure/shock, acute renal failure and a trend towards combined infections. On follow-up, they presented higher mortality and more combined MACE events, with a non-significant trend in the occurrence of cardiovascular recurrences or readmissions. CONCLUSIONS: The prevalence of neoplasms in patients with TS is high. The clinical presentation is different in relation to patients who do not have neoplasms and they probably represent a risk factor for a worse hospital and long term prognosis.

Safety and Efficacy of Prasugrel and Ticagrelor in Acute Coronary Syndrome. Results of a "Real World" Multicenter Registry.

INTRODUCTION AND OBJECTIVES: The incorporation of the new antiplatelet agents (NAA) prasugrel and ticagrelor into routine clinical practice is irregular and data from the "real world" remain scarce. We aimed to assess the time trend of NAA use and the clinical safety and efficacy of these drugs compared with those of clopidogrel in a contemporary cohort of patients with acute coronary syndromes (ACS). METHODS: A multicenter retrospective observational study was conducted in patients with ACS admitted to coronary care units and prospectively included in the ARIAM-Andalusia registry between 2013 and 2015. In-hospital rates of major cardiovascular events and bleeding with NAA vs clopidogrel were analyzed using propensity score matching and multivariate regression models. RESULTS: The study included 2906 patients: 55% received clopidogrel and 45% NAA. A total of 60% had ST-segment elevation ACS. Use of NAA significantly increased throughout the study. Patients receiving clopidogrel were older and were more likely to have comorbidities. Total mortality, ischemic stroke, and stent thrombosis were lower with NAA (2% vs 9%, P < .0001; 0.1% vs 0.5%, P = .025; 0.07% vs 0.5%, P = .025, respectively). There were no differences in the rate of total bleeding (3% vs 4%; P = NS). After propensity score matching, the mortality reduction with NAA persisted (OR, 0.37; 95%CI, 0.13 to 0.60; P < .0001) with no increase in total bleeding (OR, 1.07; 95%CI, 0.18 to 2.37; P = .094). CONCLUSIONS: In a "real world" setting, NAA are selectively used in younger patients with less comorbidity and are associated with a reduction in major cardiac events, including mortality, without increasing bleeding compared with clopidogrel.

Secondary forms of Takotsubo cardiomyopathy: A whole different prognosis.

BACKGROUND: Takotsubo syndrome (TKS) usually mimics an acute coronary syndrome. However, several clinical forms have been reported. Our aim was to assess if different stressful triggers had prognostic influence on TKS, and to establish a working classification. METHODS: We performed an analysis including patients with TKS between 2003-2013 from our prospective local database and the RETAKO National Registry, fulfilling Mayo criteria. Patients were divided in two groups regarding their potential triggers: (a) none/psychic stress as 'primary forms' and (b) physical factors (asthma, surgery, trauma, etc.) as 'secondary forms'. RESULTS: Finally, 328 patients were included, 90.2% women, with a mean age of 69.7 years. Patients were divided into primary TKS (n=265) and 63 secondary TKS groups. Age, gender, previous functional class and cardiovascular risk profile displayed no differences between groups before admission. However, primary-TKS patients suffered a main complaint of chest pain (89.4% vs 50.7%, p<0.0001) with frequent vegetative symptoms. Regarding treatment before admission, there were no differences either. During admission, differences were related to more intensive antithrombotic and anxiolytic drug use in the primary TKS group. Inotropic and mechanical ventilation use was higher in the secondary cohort. After discharge, a more frequent prescription of beta-blockers and statins in primary-TKS patients was seen. Secondary forms displayed more in-hospital stay and evolutive complications: death (hazard ratio (HR): 3.41; 95% confidence interval (CI): 1.14-10.16, p=0.02), combined event variable (MACE) (HR: 1.61; 95% CI: 1.01-2.6, p=0.04) and recurrences (HR: 1.85; 95% CI: 1.06-3.22, p=0.02). CONCLUSION: Secondary TKS could present or mark worse short and long-term prognoses in terms of mortality, recurrences and readmissions. We propose a simple working nomenclature for TKS.

Prognostic impact of clopidogrel pretreatment in patients with acute coronary syndrome managed invasively.

Pretreatment with antiP2Y12 agents before angiography in acute coronary syndrome (ACS) is associated with a reduction in thrombotic events. However, recent evidences have questioned the benefits of upstream antiP2Y12, reporting a higher incidence of bleeding. We analyzed the prognostic impact of clopidogrel pretreatment in a large cohort of invasively managed patients with ACS. In hospital, safety and efficacy of clopidogrel pretreatment were retrospectively analyzed in patients included in the ARIAM-Andalucía Registry (Analysis of Delay in Acute Myocardial Infarction). Propensity score and inverse probability of treatment weighting analysis were performed to control treatment selection bias. Results were stratified by ACS type. Sensitivity analyses were used to explore stability of the overall treatment effect. Of 9,621 patients managed invasively, 69% received clopidogrel before coronary angiography. In the ST-elevation myocardial infarction group, pretreatment was associated with a significant reduction in reinfarction (odds ratio 0.53, 95% confidence interval [CI] 0.27 to 0.96; p = 0.027), stent thrombosis (odds ratio 0.15, 95% CI 0.06 to 0.38; p <0.0001), and mortality (odds ratio 0.67, 95% CI 0.48 to 0.94; p = 0.020), with an increase in minor bleeding but remained as a net clinical benefit strategy. Those benefits were not present in patients without ST elevation (non-ST elevation ACS). The weighting and propensity analysis confirmed the same results. An interaction between pretreatment duration and bleeding was observed. In conclusion, pretreatment with clopidogrel reduced the occurrence of death and thrombotic outcomes at the cost of minor bleeding. Those benefits exclusively affected ST-elevation myocardial infarction cases. The potential benefit of routine upstream pretreatment in patients with non-ST-elevation ACS should be reappraised at the present.

Characterization of Tako-tsubo Cardiomyopathy in Spain: Results from the RETAKO National Registry.

INTRODUCTION AND AIMS: The etiology and epidemiology of tako-tsubo cardiomyopathy remain uncertain. The symptoms of this condition are often similar to those of myocardial infarction and, although it usually has a good prognosis, it is not without complications. Our aim was to characterize this disease in our setting using a dedicated registry (Spanish REgistry for TAKOtsubo cardiomyopathy). METHODS: The prospective registry included 202 incident patients in 23 hospitals from 2012 to 2013. The patients' clinical characteristics and analytical, echocardiographic, and imaging results were recorded, as were the events during follow-up. Patients were included when the attending physician considered the case proven, and incidence was calculated relative to the catheterizations requested for a presumptive diagnosis of acute coronary syndrome. RESULTS: The patients were predominantly women (90%), with a mean age of 70 years, and many had cardiovascular risk factors, such as hypertension (67%), dyslipidemia (41%), diabetes mellitus (15%), and smoking (15%). The incidence of tako-tsubo cardiomyopathy was 1.2%, and there was no clear weekly or seasonal distribution pattern. Chest pain was the predominant symptom, a triggering factor (emotional, physical, or both) was present in 72%, and most patients consulted within the first 6h after symptom onset. The median duration of hospitalization was 7 days. There were heart failure symptoms in 34.0%, arrhythmia in 26.7%, and 2.4% of patients died. CONCLUSIONS: The incidence of tako-tsubo cardiomyopathy is low. This disease primarily affects postmenopausal women, and occurs after a situation of emotional stress in more than half of affected individuals. It is characterized by anginal pain, shows no seasonal distribution, and has a good prognosis, although it is not without morbidity and mortality.

Prognostic impact of atrial fibrillation in acute coronary syndromes: results from the ARIAM registry.

AIMS: The prognostic ability of atrial fibrillation (AF) in acute coronary syndromes (ACS) is unclear. Studies regarding patient outcomes with respect to the timing of AF are scarce and conflicting. The present study aimed to determine the frequency, predictors and impact on clinical outcome of AF in patients with ACS. METHODS: We analysed 39,237 consecutive patients with ACS included in the ARIAM registry between January /2001 and December 2011. Patients with AF were compared with patients in sinus rhythm. We differentiate between new-onset AF and previous AF cases to analyse mortality and other major adverse cardiac events (MACE) during hospitalization. RESULTS: Of the patients, 2851 (7.3%) developed AF; 1568 (55%) of these were new-onset AF and 1283 (45%) had previous AF. The AF group had a higher risk profile at baseline and poorer clinical presentation at admission than non-AF patients. Compared with previous AF patients, new-onset AF presented with fewer comorbidities, including hypertension, diabetes, prior myocardial infarction, and chronic renal impairment. The inhospital mortality for new-onset AF, previous AF, and non-AF patients were 14, 11.6, and 5.2%, respectively (new-onset AF unadjusted HR 2.19, 95% CI 1.9-2.53, p<0.001; adjusted HR 1.70, 95% CI 1.12-3.4, p<0.001). After propensity score analysis, only new-onset AF persisted as an independent predictor for mortality (HR 1.62, 95% CI 1.09-2.89, p<0.001). Other MACE such as reinfarction, malignant arrhythmias, and heart failure were also more frequent in new-onset AF patients than in previous AF or non-AF patients. CONCLUSIONS: These findings suggest that the presence of new-onset AF during ACS is associated with a significant increase in mortality, even after adjusting for confounding variables.

Cor triatriatum sinistrum in an elderly man.

Divided left atrium or Cor Triatriatum, is a congenital cardiac malformation having low incidence during paediatric age, ranging between 0.1 - 0.4%. Its appearance in adulthood is even more exceptional and often inadvertently discovered, although symptomatic manifestations could entail an interesting differential diagnosis. We present an elderly patient with asymptomatic Cor Triatriatum.