Clinical profile, management and outcomes of patients with cardiogenic shock undergoing transfer between centers in Spain.

INTRODUCTION AND OBJECTIVES: The aim of this study was to analyze the clinical profile, management, and prognosis of ST segment elevation myocardial infarction-related cardiogenic shock (STEMI-CS) requiring interhospital transfer, as well as the prognostic impact of structural variables of the treating centers in this setting. METHODS: This study included patients with STEMI-CS treated at revascularization-capable centers from 2016 to 2020. The patients were divided into the following groups: group A: patients attended throughout their admission at hospitals with interventional cardiology without cardiac surgery; group B: patients treated at hospitals with interventional cardiology and cardiac surgery; and group C: patients transferred to centers with interventional cardiology and cardiac surgery. We analyzed the association between the volume of STEMI-CS cases treated, the availability of cardiac intensive care units (CICU), and heart transplant with hospital mortality. RESULTS: A total of 4189 episodes were included: 1389 (33.2%) from group A, 2627 from group B (62.7%), and 173 from group C (4.1%). Transferred patients were younger, had a higher cardiovascular risk, and more commonly underwent revascularization, mechanical circulatory support, and heart transplant during hospitalization (P<.001). The crude mortality rate was lower in transferred patients (46.2% vs 60.3% in group A and 54.4% in group B, (P<.001)). Lower mortality was associated with a higher volume of care and CICU availability (OR, 0.75, P=.009; and 0.80, P=.047). CONCLUSIONS: The proportion of transfers in patients with STEMI-CS in our setting is low. Transferred patients were younger and underwent more invasive procedures. Mortality was lower among patients transferred to centers with a higher volume of STEMI-CS cases and CICU.

Fulminant myocarditis proven by early biopsy and outcomes.

BACKGROUND AND AIMS: While endomyocardial biopsy (EMB) is recommended in adult patients with fulminant myocarditis, the clinical impact of its timing is still unclear. METHODS: Data were collected from 419 adult patients with clinically suspected fulminant myocarditis admitted to intensive care units across 36 tertiary centres in 15 countries worldwide. The diagnosis of myocarditis was histologically proven in 210 (50%) patients, either by EMB (n = 183, 44%) or by autopsy/explanted heart examination (n = 27, 6%), and clinically suspected cardiac magnetic resonance imaging confirmed in 96 (23%) patients. The primary outcome of survival free of heart transplantation (HTx) or left ventricular assist device (LVAD) at 1 year was specifically compared between patients with early EMB (within 2 days after intensive care unit admission, n = 103) and delayed EMB (n = 80). A propensity score-weighted analysis was done to control for confounders. RESULTS: Median age on admission was 40 (29-52) years, and 322 (77%) patients received temporary mechanical circulatory support. A total of 273 (65%) patients survived without HTx/LVAD. The primary outcome was significantly different between patients with early and delayed EMB (70% vs. 49%, P = .004). After propensity score weighting, the early EMB group still significantly differed from the delayed EMB group in terms of survival free of HTx/LVAD (63% vs. 40%, P = .021). Moreover, early EMB was independently associated with a lower rate of death or HTx/LVAD at 1 year (odds ratio of 0.44; 95% confidence interval: 0.22-0.86; P = .016). CONCLUSIONS: Endomyocardial biopsy should be broadly and promptly used in patients admitted to the intensive care unit for clinically suspected fulminant myocarditis.

The current clinical practice for management of post-infarction ventricular septal rupture: a European survey.

Aims: Many historical and recent reports showed that post-infarction ventricular septal rupture (VSR) represents a life-threatening condition and the strategy to optimally manage it remains undefined. Therefore, disparate treatment policies among different centres with variable results are often described. We analysed data from European centres to capture the current clinical practice in VSR management. Methods and results: Thirty-nine centres belonging to eight European countries participated in a survey, filling a digital form of 38 questions from April to October 2022, to collect information about all the aspects of VSR treatment. Most centres encounter 1-5 VSR cases/year. Surgery remains the treatment of choice over percutaneous closure (71.8% vs. 28.2%). A delayed repair represents the preferred approach (87.2%). Haemodynamic conditions influence the management in almost all centres, although some try to achieve patients stabilization and delayed surgery even in cardiogenic shock. Although 33.3% of centres do not perform coronarography in unstable patients, revascularization approaches are widely variable. Most centres adopt mechanical circulatory support (MCS), mostly extracorporeal membrane oxygenation, especially pre-operatively to stabilize patients and achieve delayed repair. Post-operatively, such MCS are more often adopted in patients with ventricular dysfunction. Conclusion: In real-life, delayed surgery, regardless of the haemodynamic conditions, is the preferred strategy for VSR management in Europe. Extracorporeal membrane oxygenation is becoming the most frequently adopted MCS as bridge-to-operation. This survey provides a useful background to develop dedicated, prospective studies to strengthen the current evidence on VSR treatment and to help improving its currently unsatisfactory outcomes.

Optimal surgical timing after post-infarction ventricular septal rupture.

BACKGROUND: Ventricular septal rupture (VSR) following acute myocardial infarction (AMI) is a dangerous condition. Surgical VSR closure is the definitive therapy, but there is controversy regarding the surgical timing and the bridging therapy between diagnosis and intervention. The objective of this study is to analyze the ideal time of surgical repair and to establish the contribution of mechanical circulatory support (MCS) devices on the prognosis. METHODS: We designed an observational, retrospective, multicenter study, selecting all consecutive patients with post-AMI VSR between January 1, 2008 and December 31, 2018, with non-exclusion criteria. The main objective of this study was to analyze the optimal timing for surgical repair of post-AMI VSR. Secondary endpoints were to determine which factors could influence mortality in the patients of the surgical group. RESULTS: A total of 141 patients were included. We identified lower mortality rates with an odds ratio of 0.3 (0.1-0.9) in patients operated on from day 4 compared with the surgical mortality in the first 24 hours after VSR diagnosis. The use of MCS was more frequent in patients treated with surgery, particularly for intra-aortic balloon pump (IABP; 79.6% vs. 37.8%, p < 0.001), but also for veno-arterial extracorporeal membrane oxygenation (VA-ECMO; 18.2% vs. 6.4%, p = 0.134). Total mortality was 91.5% for conservative management and 52.3% with surgical repair (p < 0.001). CONCLUSIONS: In our study, we observed that the lowest mortality rates in patients with surgical repair of post-AMI VSR were observed in patients operated on from day 4 after diagnosis of VSR, compared to earlier interventions.

Prevalence, Characteristics, and Outcomes of COVID-19-Associated Acute Myocarditis.

BACKGROUND: Acute myocarditis (AM) is thought to be a rare cardiovascular complication of COVID-19, although minimal data are available beyond case reports. We aim to report the prevalence, baseline characteristics, in-hospital management, and outcomes for patients with COVID-19-associated AM on the basis of a retrospective cohort from 23 hospitals in the United States and Europe. METHODS: A total of 112 patients with suspected AM from 56 963 hospitalized patients with COVID-19 were evaluated between February 1, 2020, and April 30, 2021. Inclusion criteria were hospitalization for COVID-19 and a diagnosis of AM on the basis of endomyocardial biopsy or increased troponin level plus typical signs of AM on cardiac magnetic resonance imaging. We identified 97 patients with possible AM, and among them, 54 patients with definite/probable AM supported by endomyocardial biopsy in 17 (31.5%) patients or magnetic resonance imaging in 50 (92.6%). We analyzed patient characteristics, treatments, and outcomes among all COVID-19-associated AM. RESULTS: AM prevalence among hospitalized patients with COVID-19 was 2.4 per 1000 hospitalizations considering definite/probable and 4.1 per 1000 considering also possible AM. The median age of definite/probable cases was 38 years, and 38.9% were female. On admission, chest pain and dyspnea were the most frequent symptoms (55.5% and 53.7%, respectively). Thirty-one cases (57.4%) occurred in the absence of COVID-19-associated pneumonia. Twenty-one (38.9%) had a fulminant presentation requiring inotropic support or temporary mechanical circulatory support. The composite of in-hospital mortality or temporary mechanical circulatory support occurred in 20.4%. At 120 days, estimated mortality was 6.6%, 15.1% in patients with associated pneumonia versus 0% in patients without pneumonia (P=0.044). During hospitalization, left ventricular ejection fraction, assessed by echocardiography, improved from a median of 40% on admission to 55% at discharge (n=47; P<0.0001) similarly in patients with or without pneumonia. Corticosteroids were frequently administered (55.5%). CONCLUSIONS: AM occurrence is estimated between 2.4 and 4.1 out of 1000 patients hospitalized for COVID-19. The majority of AM occurs in the absence of pneumonia and is often complicated by hemodynamic instability. AM is a rare complication in patients hospitalized for COVID-19, with an outcome that differs on the basis of the presence of concomitant pneumonia.

The impact of optimal medical therapy on patients with recurrent acute myocardial infarction: Subanalysis from the BleeMACS study.

BACKGROUND: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI. METHODS AND RESULTS: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching. CONCLUSIONS: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.

The role of perioperative cardiorespiratory support in post infarction ventricular septal rupture-related cardiogenic shock.

BACKGROUND: Current guidelines recommend emergency surgical correction in patients with post infarction ventricular septal rupture (PIVSR), but patients with multiorgan failure are commonly managed conservatively because of high surgical risk. We assessed characteristics and outcomes of operated PIVSR patients with or without the use of short-term ventricular assist devices (ST-VADs). We also assessed the impact of a ST-VAD on the performance of surgery. METHODS: We retrospectively analysed all consecutive patients with PIVSR between January 2004 and May 2017. Baseline clinical characteristics, use of ST-VAD and performance of surgery during admission were assessed. The main outcome measured was in-hospital mortality. RESULTS: A total of 28 patients were included. Mean age was 69.2 years. Most patients (20/28, 71.4%) underwent surgical repair. ST-VADs were used in 11/28 patients (39.3%). This percentage progressively increased across the study period, from 22.2% (2/9) in 2004-2011 to 58.3% (7/12) in 2015-2017 (p=0.091). Patients undergoing ST-VAD use had poorer INTERMACS status, higher values of creatinine, lactate and alanine aminotransferase and lower left ventricular ejection fraction as compared with operated patients without support. In-hospital mortality did not differ according to the use of ST-VADs in operated patients (27.3% without ST-VAD vs. 22.2% with ST-VAD, p=0.604). All five patients undergoing early preoperative venoarterial extracorporeal membrane oxygenator support and delayed surgery survived at hospital discharge. CONCLUSIONS: ST-VAD use increased in patients with PIVSR. Despite a higher risk profile in operated patients undergoing ST-VAD use, mortality was not significantly different in these patients. Early preoperative venoarterial extracorporeal membrane oxygenation should be considered for very high risk PIVSR patients.

P2Y12 inhibitors in acute coronary syndrome patients with renal dysfunction: an analysis from the RENAMI and BleeMACS projects.

AIMS: The aim of the present study was to establish the safety and efficacy profile of prasugrel and ticagrelor in real-life acute coronary syndrome (ACS) patients with renal dysfunction. METHODS AND RESULTS: All consecutive patients from RENAMI (REgistry of New Antiplatelets in patients with Myocardial Infarction) and BLEEMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registries were stratified according to estimated glomerular filtration rate (eGFR) lower or greater than 60 mL/min/1.73 m2. Death and myocardial infarction (MI) were the primary efficacy endpoints. Major bleedings (MBs), defined as Bleeding Academic Research Consortium bleeding types 3 to 5, constituted the safety endpoint. A total of 19 255 patients were enrolled. Mean age was 63 ± 12; 14 892 (77.3%) were males. A total of 2490 (12.9%) patients had chronic kidney disease (CKD), defined as eGFR <60 mL/min/1.73 m2. Mean follow-up was 13 ± 5 months. Mortality was significantly higher in CKD patients (9.4% vs. 2.6%, P < 0.0001), as well as the incidence of reinfarction (5.8% vs. 2.9%, P < 0.0001) and MB (5.7% vs. 3%, P < 0.0001). At Cox multivariable analysis, potent P2Y12 inhibitors significantly reduced the mortality rate [hazard ratio (HR) 0.82, 95% confidence interval (CI) 0.54-0.96; P = 0.006] and the risk of reinfarction (HR 0.53, 95% CI 0.30-0.95; P = 0.033) in CKD patients as compared to clopidogrel. The reduction of risk of reinfarction was confirmed in patients with preserved renal function. Potent P2Y12 inhibitors did not increase the risk of MB in CKD patients (HR 1.00, 95% CI 0.59-1.68; P = 0.985). CONCLUSION: In ACS patients with CKD, prasugrel and ticagrelor are associated with lower risk of death and recurrent MI without increasing the risk of MB.

Trends in cardiogenic shock management and prognostic impact of type of treating center.

INTRODUCTION AND OBJECTIVES: Current guidelines recommend centralizing the care of patients with cardiogenic shock in high-volume centers. The aim of this study was to assess the association between hospital characteristics, including the availability of an intensive cardiac care unit, and outcomes in patients with ST-segment elevation myocardial infarction (STEMI)-related cardiogenic shock (CS). METHODS: Discharge episodes with a diagnosis of STEMI-related CS between 2003 and 2015 were selected from the Minimum Data Set of the Spanish National Health System. Centers were classified according to the availability of a cardiology department, catheterization laboratory, cardiac surgery department, and intensive cardiac care unit. The main outcome measured was in-hospital mortality. RESULTS: A total of 19 963 episodes were identified. The mean age was 73.4±11.8 years. The proportion of patients with CS treated at hospitals with a catheterization laboratory and cardiac surgery department increased from 38.4% in 2005 to 52.9% in 2015 (P <.005). Crude- and risk-adjusted mortality rates decreased over time, from 82% to 67.1%, and from 82.7% to 66.8%, respectively (both P <.001). Coronary revascularization, either percutaneous or coronary artery bypass grafting, was independently associated with a lower mortality risk (OR, 0.29 and 0.25; both P <.001, respectively). Intensive cardiac care unit availability was associated with lower adjusted mortality rates (65.3%±7.9 vs 72±11.7; P <.001). CONCLUSIONS: The proportion of patients with STEMI-related CS treated at highly specialized centers increased while mortality decreased during the study period. Better outcomes were associated with the increased performance of revascularization procedures and access to intensive cardiac care units over time.

Development and external validation of a post-discharge bleeding risk score in patients with acute coronary syndrome: The BleeMACS score.

BACKGROUND: Accurate 1-year bleeding risk estimation after hospital discharge for acute coronary syndrome (ACS) may help clinicians guide the type and duration of antithrombotic therapy. Currently there are no predictive models for this purpose. The aim of this study was to derive and validate a simple clinical tool for bedside risk estimation of 1-year post-discharge serious bleeding in ACS patients. METHODS: The risk score was derived and internally validated in the BleeMACS (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome) registry, an observational international registry involving 15,401 patients surviving admission for ACS and undergoing percutaneous coronary intervention (PCI) from 2003 to 2014, engaging 15 hospitals from 10 countries located in America, Europe and Asia. External validation was conducted in the SWEDEHEART population, with 96,239 ACS patients underwent PCI and 93,150 without PCI. RESULTS: Seven independent predictors of bleeding were identified and included in the BleeMACS score: age, hypertension, vascular disease, history of bleeding, malignancy, creatinine and hemoglobin. The BleeMACS risk score exhibited a C-statistic value of 0.71 (95% CI 0.68-0.74) in the derivation cohort and 0.72 (95% CI 0.67-0.76) in the internal validation sample. In the SWEDEHEART external validation cohort, the C-statistic was 0.65 (95% CI 0.64-0.66) for PCI patients and 0.63 (95% CI 0.62-0.64) for non-PCI patients. The calibration was excellent in the derivation and validation cohorts. CONCLUSIONS: The BleeMACS bleeding risk score is a simple tool useful for identifying those ACS patients at higher risk of serious 1-year post-discharge bleeding. ClinicalTrials.govIdentifier: NCT02466854.

Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy.

BACKGROUND: The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. METHODS AND RESULTS: The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15 hospitals. The primary endpoint was a composite event of death and re-infarction after one year of follow-up. Bleedings were the secondary endpoint. 15,401 patients were enrolled, 926 (6.4%) in the cancer group and 14,475 (93.6%) in the group of patients without cancer. Patients with cancer were older (70.8±10.3 vs. 62.8±12.1 years, P<0.001) with more severe comorbidities and presented more frequently with non-ST-segment elevation myocardial infarction compared with patients without cancer. After one year, patients with cancer more often experienced the composite endpoint (15.2% vs. 5.3%, P<0.001) and bleedings (6.5% vs. 3%, P<0.001). At multiple regression analysis the presence of cancer was the strongest independent predictor for the primary endpoint (hazard ratio (HR) 2.1, 1.8-2.5, P<0.001) and bleedings (HR 1.5, 1.1-2.1, P=0.015). Despite patients with cancer generally being undertreated, beta-blockers (relative risk (RR) 0.6, 0.4-0.9, P=0.05), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (RR 0.5, 0.3-0.8, P=0.02), statins (RR 0.3, 0.2-0.5, P<0.001) and dual antiplatelet therapy (RR 0.5, 0.3-0.9, P=0.05) were shown to be protective factors, while proton pump inhibitors (RR 1, 0.6-1.5, P=0.9) were neutral. CONCLUSION: Cancer has a non-negligible prevalence in patients with acute coronary syndrome undergoing percutaneous coronary intervention, with a major risk of cardiovascular events and bleedings. Moreover, these patients are often undertreated from clinical despite medical therapy seems to be protective. Registration:The BleeMACS project (NCT02466854).

Predictors of Late Reperfusion in STEMI Patients Undergoing Primary Angioplasty. Impact of the Place of First Medical Contact.

INTRODUCTION AND OBJECTIVES: The benefit of primary angioplasty may be reduced if there are delays to reperfusion. Identification of the variables associated with these delays could improve health care. METHODS: Analysis of the Codi Infart registry of Catalonia and of the time to angioplasty depending on the place of first medical contact. RESULTS: In 3832 patients analyzed, first medical contact took place in primary care centers in 18% and in hospitals without a catheterization laboratory in 37%. Delays were longer in these 2 groups than in patients attended by the outpatient emergency medical system or by hospitals with a catheterization laboratory (P < .0001, results in median): first medical contact to reperfusion indication time was 42minutes in both (overall 35minutes); first medical contact to artery opening time was 131 and 143minutes, respectively (overall 121minutes); total ischemia time was 230 and 260minutes (overall 215minutes). First medical contact to artery opening time > 120minutes was strongly associated with first medical contact in a center without a catheterization laboratory (OR, 4.96; 95% confidence interval, 4.14-5.93), and other factors such as age, previous coronary surgery, first medical contact during evening hours, nondiagnostic electrocardiogram, and Killip class ≥ III. Mortality at 30 days and 1 year was 5.6% and 8.7% and was independently associated with age, longer delay to angioplasty, Killip class ≥ II, and first medical contact in a center with a catheterization laboratory. CONCLUSIONS: In more than 50% of patients requiring primary angioplasty, the first medical contact occurs in centers without a catheterization laboratory, which is an important predictor of delay from diagnosis to artery opening.

Optimal Medical Therapy in Patients with Malignancy Undergoing Percutaneous Coronary Intervention for Acute Coronary Syndrome: a BleeMACS Sub-Study.

OBJECTIVE: Our objective was to define the most appropriate treatment for acute coronary syndrome (ACS) in patients with malignancy. METHODS AND RESULTS: The BleeMACS project is a worldwide multicenter observational prospective registry in 16 hospitals enrolling patients with ACS undergoing percutaneous coronary intervention. Primary endpoints were death, re-infarction, and major adverse cardiac events (MACE; composite of death and re-infarction) after 1 year of follow-up. The secondary endpoint was bleeding events during follow-up. We performed sub-study analyses according to whether ß-blockers (BBs), angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), statins, or proton pump inhibitors (PPIs) were prescribed at discharge. We also calculated the propensity score for optimal medical therapy (OMT; combination of BB, ACEI/ARB, and statins). The study included 926 patients. According to the multivariate analysis, ACEIs/ARBs (hazard ratio [HR] 0.58, 95 % confidence interval [CI] 0.36-1.94; p = 0.03) and statins (HR 0.37, 95 % CI 0.23-0.61; p < 0.01) reduced the risk of MACE, while the effects of BBs (HR 0.85, 95 % CI 0.55-1.32; p = 0.48) and PPIs (HR 1.33, 95 % CI 0.83-2.12; p = 0.23) were not significant. OMT was prescribed at discharge in 300 (32.4 %) patients; after propensity score analysis, OMT showed a significant reduction in death (3 % vs. 12.5 %, HR 0.21, 95 % CI 0.1-0.4; log-rank p < 0.001) and MACE (6.7 vs. 15.2 %, log-rank p = 0.01). CONCLUSION: In patients with ACS and malignancy, OMT reduces the risk of adverse events at 1 year; in particular, ACEIs/ARBs and statins were the most protective drugs. (Clinical trials identifier: NCT02466854).

[Impact of concomitant use of P2Y12 inhibitors and proton pump inhibitors on ischemia events in patients with acute coronary syndrome in real world].

Objective: The study aimed to analyze the impact of concomitant administration of P2Y12 inhibitors and PPIs on ischemia events in patients with acute coronary syndrome (ACS) after percutaneous coronary intervention (PCI). Methods: We retrospectively analyzed data from a international, multi-center registry between 2003 and 2014 in patients with ACS after PCI, grouped the cohort into patients receiving PPIs or no PPIs and assessed 1-year clinical endpoint (all-cause death/re-infarction). Meanwhile, we grouped the cohort into patients receiving clopidogrel or ticagrelor, and compared the impact of concomitant administration of PPIs and clopidogrel or ticagrelor on 1-year clinical endpoint. Results: Of 9 429 patients in the final cohort, 54.8% (n=5 165) was prescribed a PPI at discharge. Patients receiving a PPI were more likely to have comorbidities. No association was observed between PPI use and the clinical endpoint (HR 1.00, 95% CI 0.86-1.18). Meanwhile, no association was found between PPI use and the clinical endpoint in patients receiving either clopidogrel or ticagrelor. And the clinical endpoint in patients administrated of clopidogrel and PPIs had no difference with that of ticagrelor and PPIs. Conclusions: In patients with ACS following PCI, increased risk of ischemia event was not found in the concomitant use of PPIs and P2Y12 inhibitors, and especially, compared with ticagrelor, clopidogrel was found no association with ischemia events when concomitant administrated with PPIs.

[Body mass index and prognosis in the elderly patients with acute coronary syndromes]. / Índice de masa corporal y pronóstico en pacientes ancianos con síndrome coronario agudo.

BACKGROUND AND OBJECTIVE: Little information exists about the prognostic impact of body mass index (BMI) in the elderly with acute coronary syndromes (ACS). We aimed to prospectively assess the association between BMI and midterm mortality in consecutive elderly patients with ACS. PATIENTS AND METHOD: We included consecutive ACS patients aged 75 years or older admitted to the Coronary Care Unit. Patients were stratified into 5 BMI subgroups (<20, 20-24.9, 25-29.9, 30-35, > 35 kg/m(2)). Primary endpoint was overall midterm mortality. Analyses were performed by Cox regression method. RESULTS: During the study period 600 patients were admitted, of whom 579 had known BMI values. Low weight patients (BMI<20 kg/m(2)) were older, with higher prevalence of vasculopathy and lower creatinine clearance. Median follow up was 315 days. Patients with BMI< 20 kg/m(2) had higher mortality as compared to the rest of groups. Adjusted analysis showed an attenuation of these differences, while maintaining significance for the groups of BMI 20-24.9 and 30-35 kg/m(2). CONCLUSIONS: The association between BMI and mortality was mainly due to worse prognosis in low weight patients. Prospective assessment of comorbidities and other variables linked to ageing should contribute to better understand the association between BMI and mortality.

Anthracycline-mediated cardiomyopathy: Basic molecular knowledge for the cardiologist / Miocardiopatía inducida por antraciclinas: conocimientos moleculares básicos para el cardiólogo

Anthracyclines are cytostatic antibiotics discovered almost half a century ago exerting their action through inhibition of topoisomerase II. The two most representative drugs are doxorubicin and daunorubicin and they have been proven as useful antineoplastics and are widely prescribed in daily oncology practice; unfortunately, cardiotoxicity has been a limiting factor when it comes to their use. Diverse mechanisms have been involved in anthracycline cardiotoxicity, none of which are capable of causing the whole clinical picture by itself. Traditionally, reactive oxygen species (ROS) have received more attention, although recently basic research has proven other factors to be as important as ROS. These factors mainly involve sarcomeric structure disruption, toxic accumulation of metabolites, iron metabolism, energetic alterations and inflammation. The role of genetics has been studied by some groups, although a clear genotype-response relationship is yet to be elucidated. With the improved survival from different oncologic diseases we are witnessing more cases of chemotherapy-induced cardiotoxicity and the advent of new anticancer drugs poses several challenges for the cardiologist, highlighting the importance of a deep knowledge of the main mechanisms inducing this toxicity.

Hace casi medio siglo se descubrieron las antraciclinas; estas son antibióticos citostáticos inhibidores de la topoisomerasa II. Los 2 fármacos más representativos de este grupo son la doxorrubicina y la daunorrubicina. Estos fármacos han demostrado ser eficaces antineoplásicos y han sido ampliamente utilizados en la práctica oncológica. Desafortunadamente, la cardiotoxicidad sigue siendo un elemento limitante para su uso. Los mecanismos mediante los cuales estos fármacos ocasionan cardiotoxicidad son múltiples pero ninguno de ellos de forma individual es capaz de explicar el cuadro clínico por completo. Casi siempre se ha considerado que la formación de especies reactivas de oxígeno era responsable de gran parte de la toxicidad, sin embargo la experimentación básica reciente ha demostrado que hay otros factores, entre los que destacan las alteraciones en la estructura sarcomérica, la acumulación de metabolitos tóxicos, las alteraciones del metabolismo del hierro o de los mecanismos energéticos, y la liberación de mediadores de inflamación. Por otra parte, diversos grupos han investigado la intervención que la genética podría tener en el desarrollo de esta enfermedad, si bien no se puede definir aún una clara correlación genotipo-respuesta. Con el aumento de la supervivencia por el tratamiento de diversas enfermedades oncológicas, se están detectando más casos de cardiotoxicidad mediada por quimioterapia; y con la aparición de nuevos fármacos quimioterápicos se añaden nuevos retos, con lo que se demuestra la importancia del estudio profundo de los mecanismos causales.

Anthracycline-mediated cardiomyopathy: basic molecular knowledge for the cardiologist.

Anthracyclines are cytostatic antibiotics discovered almost half a century ago exerting their action through inhibition of topoisomerase II. The two most representative drugs are doxorubicin and daunorubicin and they have been proven as useful antineoplastics and are widely prescribed in daily oncology practice; unfortunately, cardiotoxicity has been a limiting factor when it comes to their use. Diverse mechanisms have been involved in anthracycline cardiotoxicity, none of which are capable of causing the whole clinical picture by itself. Traditionally, reactive oxygen species (ROS) have received more attention, although recently basic research has proven other factors to be as important as ROS. These factors mainly involve sarcomeric structure disruption, toxic accumulation of metabolites, iron metabolism, energetic alterations and inflammation. The role of genetics has been studied by some groups, although a clear genotype-response relationship is yet to be elucidated. With the improved survival from different oncologic diseases we are witnessing more cases of chemotherapy-induced cardiotoxicity and the advent of new anticancer drugs poses several challenges for the cardiologist, highlighting the importance of a deep knowledge of the main mechanisms inducing this toxicity.