Project description:Cardioprotection refers to a strategy aimed at enhancing survival pathways in the injured yet salvageable myocardium following ischemia-reperfusion. Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor that can be targeted following reperfusion, to induce a cardioprotective signaling through the activation of the reperfusion injury salvage kinase (RISK) pathway. The data from preclinical studies with non-selective and selective LRP1 agonists are promising, showing a large therapeutic window for intervention to reduce infarct size after ischemia-reperfusion. A pilot clinical trial with plasma derived α1-antitrypsin (AAT), a naturally occurring LRP1 agonist, supports the translational value of LRP1 as a novel therapeutic target for cardioprotection. A phase I study with a selective LRP1 agonist has been completed showing no toxicity. These findings may open the way to early phase clinical studies with pharmacologic LRP1 activation in patients with acute myocardial infarction (AMI).
Project description:Over the past few decades, advances in pharmacological, catheter-based, and surgical reperfusion have improved outcomes for patients with acute myocardial infarctions. However, patients with large infarcts or those who do not receive timely revascularization remain at risk for mechanical complications of acute myocardial infarction. The most commonly encountered mechanical complications are acute mitral regurgitation secondary to papillary muscle rupture, ventricular septal defect, pseudoaneurysm, and free wall rupture; each complication is associated with a significant risk of morbidity, mortality, and hospital resource utilization. The care for patients with mechanical complications is complex and requires a multidisciplinary collaboration for prompt recognition, diagnosis, hemodynamic stabilization, and decision support to assist patients and families in the selection of definitive therapies or palliation. However, because of the relatively small number of high-quality studies that exist to guide clinical practice, there is significant variability in care that mainly depends on local expertise and available resources.
Project description:Despite advanced therapies, the mortality of patients with myocardial infarction (MI) complicated by cardiogenic shock (CS) remains around 50%. Mechanical complications of MI are rare nowadays but associated with high mortality in patients who present with CS. Different treatment strategies and mechanical circulatory support (MCS) devices have been increasingly used to improve the grim prognosis of refractory CS. This article discusses current evidence regarding the use of MCS in MI complicated by CS, ventricular septal rupture, free wall rupture and acute mitral regurgitation. Device selection should be tailored according to the cause and severity of CS. Early MCS initiation and multidisciplinary team cooperation is mandatory for good results. MCS associated bleeding remains a major complication and an obstacle to better outcomes. Ongoing prospective randomized trials will improve current knowledge regarding MCS indications, timing, and patient selection in the coming years.
Project description:BackgroundMechanical complications represent an important cause of mortality in myocardial infarction (MI) patients. This is a nationwide study performed to evaluate possible changes in epidemiology or prognosis of these complications with current available strategies.MethodsInformation was obtained from the minimum basis data set of the Spanish National Health System, including all hospitalizations for acute myocardial infarction (AMI) from 2010 to 2015. Risk-standardized in-hospital mortality ratio was calculated using multilevel risk adjustment models.ResultsA total of 241,760 AMI episodes were analyzed, MI mechanical complications were observed in 842 patients: cardiac tamponade in 587, ventricular septal rupture in 126, and mitral regurgitation due to papillary muscle or chordae tendineae rupture in 155 (there was more than one complication in 21 patients). In-hospital mortality was 59.5%. On multivariate adjustment, variables with significant impact on in-hospital mortality were: age (OR 1.06; 95% CI 1.04-1.07; p < 0.001), ST-segment elevation AMI (OR 2.91; 95% CI 1.88-4.5; p < 0.001), cardiogenic shock (OR 2.35; 95% CI 1.66-3.32; p < 0.001), cardio-respiratory failure (OR 3.48; 95% CI 2.37-5.09; p < 0.001), and chronic obstructive pulmonary disease (OR 1.85; 95% CI 1.07-3.20; p < 0.001). No significant trends in risk-adjusted in-hospital mortality were detected (IRR 0.997; p = 0.109). Cardiac intensive care unit availability and more experience with mechanical complications management were associated with lower adjusted mortality rates (56.7 ± 5.8 vs. 60.1 ± 4.5; and 57 ± 6.1 vs. 59.9 ± 5.6, respectively; p < 0.001).ConclusionsMechanical complications occur in 3.5 per thousand AMI, with no significant trends to better survival over the past few years. Advanced age, cardiogenic shock and cardio-respiratory failure are the most important risk factors for in-hospital mortality. Higher experience and specialized cardiac intensive care units are associated with better outcomes.
Project description:Although numerous therapies are widely applied clinically and stem cells and/or biomaterial based in situ implantations have achieved some effects, few of these have observed robust myocardial regeneration. The beneficial effects on cardiac function and structure are largely acting through paracrine signaling, which preserve the border-zone around the infarction, reduce apoptosis, blunt adverse remodeling, and promote angiogenesis. Ionic extracts from biomaterials have been proven to stimulate paracrine effects and promote cell-cell communications. Here, the paracrine stimulatory function of bioactive ions derived from biomaterials is integrated into the clinical concept of administration and proposed "ion therapy" as a novel strategy for myocardial infarction. In vitro, silicon- enriched ion extracts significantly increase cardiomyocyte viability and promote cell-cell communications, thus stimulating vascular formation via a paracrine effect under glucose/oxygen deprived conditions. In vivo, by intravenous injection, the bioactive silicon ions act as "diplomats" and promote crosstalk in myocardial cells, stimulate angiogenesis, and improve cardiac function post-myocardial infarction.
Project description:BackgroundThe study aims to assess characteristics and outcomes of patients suffering a mechanical complication (MC) after ST-segment elevation myocardial infarction (STEMI) in a contemporary cohort of patients in the percutaneous coronary intervention era.Methods and resultsThis retrospective single-center cohort study encompasses 2508 patients admitted with STEMI between March 9, 2009 and June 30, 2014. A total of 26 patients (1.1%) suffered a mechanical complication: ventricular septal rupture (VSR) in 17, ventricular free wall rupture (VFWR) in 2, a combination of VSD and VFWR in 2, and papillary muscle rupture (PMR) in 5 patients. Older age (74.5 ± 10.4 years versus 63.9 ± 13.1 years, p < 0.001), female sex (42.3% versus 23.3%, p = 0.034), and a longer latency period between symptom onset and angiography (> 24h: 42.3% versus 16.2%, p = 0.002) were more frequent among patients with MC as compared to patients without MC. The majority of MC patients had multivessel disease (77%) and presented in cardiogenic shock (Killip class IV: 73.1%). Nine patients (7 VSR, 2 VFWR & VSR) were treated conservatively and died. Out of the remaining 10 VSR patients, four underwent surgery, three underwent implantation of an occluder device, and another three patients had surgical repair following occluder device implantation. All patients with isolated VFWR and PMR underwent emergency surgery. At 30 days, mortality for VSR, VFWR, VFWR & VSR and PMR amounted to 71%, 50%, 100% and 0%, respectively.ConclusionsDespite advances in the management of STEMI patients, mortality of mechanical complications stays considerable in this contemporary cohort. Older age, female sex, and a prolonged latency period between symptom onset and angiography are associated with the occurrence of these complications.
Project description:AimsCOVID-19 has dramatically impacted the healthcare system. Evidence from previous studies suggests a decline in in-hospital admissions for acute myocardial infarction (AMI) during the pandemic. However, the effect of the pandemic on mechanical complications (MC) in acute ST-segment elevation myocardial infarction (STEMI) has not been comprehensively investigated. Therefore, we evaluated the impact of the pandemic on MC and in-hospital outcomes in STEMI during the second wave, in which there was a huge SARS-CoV-2 diffusion in Italy.Methods and resultsBased on a single center cohort of AMI patients admitted with STEMI between February 1, 2019, and February 28, 2021, we compared the characteristics and outcomes of STEMI patients treated during the pandemic vs. those treated before the pandemic. In total, 479 STEMI patients were included, of which 64.5% were during the pandemic. Relative to before the pandemic, primary percutaneous coronary intervention (PCI) declined (87.7 vs. 94.7%, p = 0.014) during the pandemic. Compared to those admitted before the pandemic (10/2019 to 2/2020), STEMI patients admitted during the second wave (10/2020 to 2/2021) presented with a symptom onset-to-door time greater than 24 h (26.1 vs. 10.3%, p = 0.009) and a reduction of primary PCI (85.2 vs. 97.1%, p = 0.009). MC occurred more often in patients admitted during the second wave of the pandemic than in those admitted before the pandemic (7.0 vs. 0.0%, p = 0.032). In-hospital mortality increased during the second wave (10.6 vs. 2.9%, p = 0.058).ConclusionAlthough the experience gained during the first wave and a more advanced hub-and-spoke system for cardiovascular emergencies persists, late hospitalizations and a high incidence of mechanical complications in STEMI were observed even in the second wave.
Project description:There are limited data on complications in acute myocardial infarction (AMI) admissions receiving extracorporeal membrane oxygenation (ECMO). Adult (>18 years) admissions with AMI receiving ECMO support were identified from the National Inpatient Sample database between 2000 and 2016. Complications were classified as vascular, lower limb amputation, hematologic, and neurologic. Outcomes of interest included temporal trends, in-hospital mortality, hospitalization costs, and length of stay. In this 17-year period, in ~10 million AMI admissions, ECMO support was used in 4608 admissions (<0.01%)-mean age 59.5 ± 11.0 years, 75.7% men, 58.9% white race. Median time to ECMO placement was 1 (interquartile range [IQR] 0-3) day. Complications were noted in 2571 (55.8%) admissions-vascular 6.1%, lower limb amputations 1.1%, hematologic 49.3%, and neurologic 9.9%. There was a steady increase in overall complications during the study period (21.1% in 2000 vs. 70.5% in 2016). The cohort with complications, compared to those without complications, had comparable adjusted in-hospital mortality (60.7% vs. 54.0%; adjusted odds ratio 0.89 [95% confidence interval 0.77-1.02]; p = 0.10) but longer median hospital stay (12 [IQR 5-24] vs. 7 [IQR 3-21] days), higher median hospitalization costs ($458,954 [IQR 260,522-737,871] vs. 302,255 [IQR 173,033-623,660]), fewer discharges to home (14.7% vs. 17.9%), and higher discharges to skilled nursing facilities (44.1% vs. 33.9%) (all p < 0.001). Over half of all AMI admissions receiving ECMO support develop one or more severe complications. Complications were associated with higher resource utilization during and after the index hospitalization.
Project description:Microvascular obstruction (MVO) is a recognised phenomenon following mechanical reperfusion in patients presenting with ST-segment elevation myocardial infarction (STEMI). Invasive and non-invasive modalities to detect and measure the extent of MVO vary in their accuracy, suggesting that this phenomenon may reflect a spectrum of pathophysiological changes at the level of coronary microcirculation. The importance of detecting MVO lies in the observation that its presence adds incremental risk to patients following STEMI treatment. This increased risk is associated with adverse cardiac remodelling seen on cardiac imaging, increased infarct size, and worse patient outcomes. This review provides an outline of the pathophysiology, clinical implications, and prognosis of MVO in STEMI. It describes historic and novel pharmacological and non-pharmacological therapies to address this phenomenon in conjunction with primary PCI.