Molecular signature of cardiogenic shock.

The incidence of cardiogenic shock (CS) has increased remarkably over the past decade and remains a challenging condition with mortality rates of ∼50%. Cardiogenic shock encompasses cardiac contractile dysfunction; however, it is also a multiorgan dysfunction syndrome, often complicated by a systemic inflammatory response with severe cellular and metabolic dysregulations. Here, we review the evidence on the biochemical manifestations of CS, elaborating on current gold standard biomarkers and novel candidates from molecular signatures of CS. Glucose and lactate, both identified over a century ago, remain the only clinically used biomarkers in current predictive risk scores. Novel genomic, transcriptomic, and proteomic data are discussed, and a recently reported molecular score derived from unbiased proteomic discovery, the CS4P, which includes liver fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1 is comprehensively described. Recent advances in -omics technologies provide new insight into a more holistic molecular signature of CS. Thus, we need to open new diagnostic and therapeutic avenues if we aim to improve outcomes.

Comorbidity and low use of new antiplatelets in acute coronary syndrome.

INTRODUCTION: Despite the use of the new generation P2Y12 inhibitors (Ticagrelor and Prasugrel) with aspirin is the recommended therapy in acute NSTE-ACS patients, their current use in clinical practice remains quite low and might be related, among several variables, with increased comorbidity burden. We aimed to assess the prevalence of these treatments and whether their use could be associated with comorbidity. METHOD: A multicentric prospective registry was conducted at 8 Cardiac Intensive Care Units (October 2017-April 2018) in patients admitted with non ST elevation myocardial infarction. Antithrombotic treatment was recorded and the comorbidity risk was assessed using the Charlson Comorbidity Index. We created a multivariate model to identify the independent predictors of the use of new inhibitors of P2Y12. RESULTS: A total of 629 patients were included, median age 67 years, 23.2% women, 359 patients (57.1%) treated with clopidogrel and 40.6% with new P2Y12 inhibitors: ticagrelor (228 patients, 36.2%) and prasugrel (30 patients, 4.8%). Among the patients with very high comorbidity (Charlson Score > 6) clopidogrel was the drug of choice (82.6%), meanwhile in patients with low comorbility (Charlson Score 0-1) was the ticagrelor or prasugrel (63.6%). Independent predictors of the use of ticagrelor or prasugrel were a low Charlson Comorbidity Index, a low CRUSADE score and the absence of prior bleeding. CONCLUSION: Antiplatelet treatment with Ticagrelor or Pasugrel was low in patients admitted with NSTE-ACS. Comorbidity calculated with Charlson Comorbidity Index was a powerful predictor of the use of new generation P2Y12 inhibitors in this population.

Protein-based cardiogenic shock patient classifier.

AIMS: Cardiogenic shock (CS) is associated with high short-term mortality and a precise CS risk stratification could guide interventions to improve patient outcome. Here, we developed a circulating protein-based score to predict short-term mortality risk among patients with CS. METHODS AND RESULTS: Mass spectrometry analysis of 2654 proteins was used for screening in the Barcelona discovery cohort (n = 48). Targeted quantitative proteomics analyses (n = 51 proteins) were used in the independent CardShock cohort (n = 97) to derive and cross-validate the protein classifier. The combination of four circulating proteins (Cardiogenic Shock 4 proteins-CS4P), discriminated patients with low and high 90-day risk of mortality. CS4P comprises the abundances of liver-type fatty acid-binding protein, beta-2-microglobulin, fructose-bisphosphate aldolase B, and SerpinG1. Within the CardShock cohort used for internal validation, the C-statistic was 0.78 for the CardShock risk score, 0.83 for the CS4P model, and 0.84 (P = 0.033 vs. CardShock risk score) for the combination of CardShock risk score with the CS4P model. The CardShock risk score with the CS4P model showed a marked benefit in patient reclassification, with a net reclassification improvement (NRI) of 0.49 (P = 0.020) compared with CardShock risk score. Similar reclassification metrics were observed in the IABP-SHOCK II risk score combined with CS4P (NRI =0.57; P = 0.032). The CS4P patient classification power was confirmed by enzyme-linked immunosorbent assay (ELISA). CONCLUSION: A new protein-based CS patient classifier, the CS4P, was developed for short-term mortality risk stratification. CS4P improved predictive metrics in combination with contemporary risk scores, which may guide clinicians in selecting patients for advanced therapies.

Acute-phase dynamics and prognostic value of growth differentiation factor-15 in ST-elevation myocardial infarction.

Background Growth differentiation factor 15 (GDF-15) in ST-elevation myocardial infarction (STEMI) is prognostic in first-generation radioimmunoassays. We examined GDF-15 temporal dynamics in STEMI and its predictive value using a first fully automated GDF-15 electrochemiluminescence assay. Methods In this prospective study, circulating GDF-15 concentration was measured at admission (0 h), 12 h and 24 h in 1026 consecutive STEMI patients treated between February 2011 and May 2016 with primary percutaneous coronary intervention. GDF-15 dynamics (0 h, 12 h, 24 h) and predictive value (30 days and 3 years) were examined. Results Median GDF-15 concentration was 1443 pg/mL at 0 h, 1731 pg/mL at 12 h and 1510 pg/mL at 24 h (p<0.001). During follow-up, 94 patients died (9.2%) and 154 (15.0%) were hospitalized. GDF-15 was a strong predictor of 30-day mortality (hazard ratio [HR] 1.76, 95% confidence interval [CI], 1.33-2.34 at 0 h; HR 2.99 [95% CI, 2.18-4.09] at 12 h, and HR 1.97 [95% CI, 1.47-2.63] at 24 h) in multivariable Cox proportional hazards models. GDF-15 improved discrimination and reclassification of a clinical risk model. GDF-15 was also associated with 3-year mortality (HR 1.31 [95% CI, 1.04-1.65] at 0 h, HR 1.42 [95% CI, 1.10-1.84] at 12 h, and HR 1.51 [95% CI, 1.16-1.96] at 24 h) and 3-year composite of mortality and cardiovascular hospitalization (HR 1.17 [95% CI, 1.01-1.37] at 0 h, HR 1.20 [95% CI, 1.02-1.42] at 12 h, and HR 1.27 [95% CI, 1.08-1.50] at 24 h). Conclusions GDF-15 peaked at 12 h and remained elevated at 24 h in STEMI. GDF-15 measurement during the first 24 h in STEMI is valuable for predicting especially short- but also long-term outcomes, and may be a useful addition to risk stratification.

Secondary prevention strategies after an acute ST-segment elevation myocardial infarction in the AMI code era: beyond myocardial mechanical reperfusion.

BACKGROUND: The AMI code is a regional network enhancing a rapid and widespread access to reperfusion therapy (giving priority to primary angioplasty) in patients with acute ST-segment elevation myocardial infarction (STEMI). We aimed to assess the long-term control of conventional cardiovascular risk factors after a STEMI among patients included in the AMI code registry. DESIGN AND METHODS: Four hundred and fifty-four patients were prospectively included between June-2009 and April-2013. Clinical characteristics were collected at baseline. The long-term control of cardiovascular risk factors and cardiovascular morbidity/mortality was assessed among the 6-months survivors. RESULTS: A total of 423 patients overcame the first 6 months after the STEMI episode, of whom 370 (87%) underwent reperfusion therapy (363, 98% of them, with primary angioplasty). At 1-year follow-up, only 263 (62%) had adequate blood pressure control, 123 (29%) had LDL-cholesterol within targeted levels, 126/210 (60%) smokers had withdrawn from their habit and 40/112 (36%) diabetic patients had adequate glycosylated hemoglobin levels. During a median follow-up of 20 (11-30) months, cumulative mortality of 6 month-survivors was 6.1%, with 9.9% of hospital cardiovascular readmissions. The lack of assessment of LDL and HDL-cholesterol were significantly associated with higher mortality and cardiovascular readmission rates. CONCLUSIONS: Whereas implementation of the AMI code resulted in a widespread access to rapid reperfusion therapy, its long-term therapeutic benefit may be partially counterbalanced by a manifestly suboptimal control of cardiovascular risk factors. Further efforts should be devoted to secondary prevention strategies after STEMI.

Early ST elevation myocardial infarction in non-capable percutaneous coronary intervention centres: in situ fibrinolysis vs. percutaneous coronary intervention transfer.

AIMS: The preferred reperfusion strategy for early ST elevation myocardial infarction (STEMI, defined as time from symptoms onset ≤120 min) in non-capable percutaneous coronary intervention (PCI) centres remains controversial. We sought to compare mortality of in situ fibrinolysis vs. PCI transfer in a real-life consecutive cohort of early STEMI. METHODS AND RESULTS: Prospective multicentre STEMI registry (Catalonia 'Codi IAM' network) of all-comers in a non-capable PCI centre with symptom onset to first medical contact (FMC) <120 min. Two groups were identified: in situ fibrinolysis and transfer to a PCI-capable centre. Primary endpoint was 30-day mortality. We included 2470 patients, of whom 2227 (90.2%) and 243 (9.8%) comprised the transfer and fibrinolysis groups, respectively. In the fibrinolysis group, diagnostic and system delays were shorter (24 vs. 31 min, P < 0.001; 45 vs. 119 min, P < 0.001, respectively). Thirty-day mortality was 7.7 and 5.1% in fibrinolysis and transfer groups, respectively (P = 0.09). However, patients in the transfer group whose time FMC-device was achieved within 140 min were associated with significantly lower mortality (2.0% for FMC-device <99 min, and 4.6% for FMC-device 99-140 min; P < 0.01 and P = 0.03, respectively vs. fibrinolysis). In multivariable logistic regression analysis, reperfusion with fibrinolysis was an independent 30-day mortality predictive factor (odds ratio: 1.91, 95% confidence interval: 1.01-3.50; P = 0.04), together with age and Killip-Kimball class (both P < 0.001). CONCLUSIONS: In early STEMI patients assisted in non-capable PCI centres, in situ fibrinolysis had worse prognosis than patient transfer. Transfer to a PCI-capable centre seems recommended in patients with FMC-device delay <140 min.

Ten-year prognosis of acute atrial fibrillation in ST-elevation myocardial infarction: recurrence and risk stroke.

BACKGROUND: Atrial fibrillation (AF) often complicates ST elevation acute myocardial infarction (STEMI), with associated risks including stroke and mortality. Anticoagulation therapy for these patients and AF prognosis remains controversial. The aim was to evaluate long-term prognosis of STEMI patients complicated with AF in the acute phase. METHODS: We performed a retrospective analysis on a prospective register involving 4,184 patients admitted for STEMI to the intensive cardiac care unit of 2 tertiary centres from 2007 to 2015. Patients with pre-existing permanent AF were excluded. Out of these, 269 (6.4%) patients developed AF within the first 48 hours after STEMI and were matched with a control group based on age and left ventricular ejection fraction (LVEF). RESULTS: After matching, a total of 470 patients were included (n=235, AF-STEMI; n=235, control group). Mean age 69.0 years, and 31.7% women. No differences were found in gender, cardiovascular risk factors or ischemic heart disease. AF-STEMI patients experienced more sustained ventricular tachycardia, advanced atrioventricular block, heart failure, and cardiogenic shock. In-hospital mortality was also higher in AF-STEMI patients (11.9% vs 7.2%, p=0.008). After 10-years follow-up, the AF-STEMI group had remained with higher mortality (50.5% vs. 36.2%; p=0.003) and a greater recurrence of AF (44.2% vs. 14.7%; p<0.001), without differences in stroke incidence (10.1% vs. 9.3%). CONCLUSIONS: As a conclusion, patients with AF complicating STEMI have higher rates of heart failure, cardiogenic shock, and in-hospital mortality. After a 10-year follow-up, they exhibit a high risk of AF recurrence and mortality, with no significant differences in stroke incidence.

Mechanical complications in STEMI: prevalence and mortality trends in the primary PCI era. The Ruti-STEMI registry.

INTRODUCTION AND OBJECTIVES: Mechanical complications confer a dreadful prognosis in ST-elevation myocardial infarction (STEMI). Their prevalence and prognosis are not well-defined in the current era of primary percutaneous coronary intervention (pPCI) reperfusion networks. We aimed to analyze prevalence and mortality trends of post-STEMI mechanical complications over 2 decades, before and after the establishment of pPCI networks. METHODS: Prospective, consecutive registry of STEMI patients within a region of 850 000 inhabitants over 2 decades: a pre-pPCI period (1990-2000) and a pPCI period (2007-2017). We analyzed the prevalence of mechanical complications, including ventricular septal rupture, papillary muscle rupture, and free wall rupture (FWR). Twenty eight-day and 1-year mortality trends were compared between the 2 studied decades. RESULTS: A total of 6033 STEMI patients were included (pre-pPCI period, n=2250; pPCI period, n=3783). Reperfusion was supported by thrombolysis in the pre-pPCI period (99.1%) and by pPCI in in the pPCI period (95.7%). Mechanical complications developed in 135 patients (2.2%): ventricular septal rupture in 38 patients, papillary muscle rupture in 24, and FWR in 73 patients. FWR showed a relative reduction of 60% in the pPCI period (0.8% vs 2.0%, P<.001), without significant interperiod changes in the other mechanical complications. After multivariate adjustment, FWR remained higher in the pre-pPCI period (OR, 1.93; 95%CI, 1.10-3.41; P=.023). At 28 days and 1 year, mortality showed no significant changes in all the mechanical complications studied. CONCLUSIONS: The establishment of regional pPCI networks has modified the landscape of mechanical complications in STEMI. FWR is less frequent in the pPCI era, likely due to reduced transmural infarcts.

Meteorin-like protein is associated with a higher risk profile and predicts a worse outcome in patients with STEMI.

INTRODUCTION AND OBJECTIVES: Meteorin-like protein (Metrnl) is a cytokine involved in the attenuation of inflammation. In patients with heart failure, high levels of this biomarker are associated with a worse outcome. In this study, we evaluated the circulating levels and prognostic value of Metrnl in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We enrolled STEMI patients undergoing primary percutaneous coronary intervention. Circulating Metrnl levels were measured in peripheral blood 12hours after symptom onset. The primary endpoint was a composite of all-cause mortality or nonfatal myocardial infarction (MI) at 3 years. RESULTS: We studied 381 patients (mean age 61 years, 21% female, 8% Killip class III/IV). Metrnl levels were associated with age, cardiovascular risk factors and the extent of coronary artery disease, as well as with STEMI complications, particularly heart failure and cardiogenic shock. Multivariable Cox regression analysis revealed that Metrnl independently predicted all-cause death or nonfatal MI at 3 years (HR, 1.86; 95%CI, 1.23-2.81; P=.003). Moreover, patients in the highest tertile (> 491.6 pg/mL) were at higher risk for the composite endpoint than those in the lowest tertiles (HR, 3.24; 95%CI, 1.92-5.44; P <.001), even after adjustment by age, diabetes mellitus, cardiac arrest, Killip-Kimball III/IV class, left ventricular ejection fraction, and creatinine clearance (HR, 1.90; 95%CI, 1.10-3.29; P=.021). CONCLUSIONS: Circulating Metrnl levels are associated with complications during the acute phase of STEMI and independently predict a worse outcome in these patients.

Time course, factors related to, and prognostic impact of venoarterial extracorporeal membrane flow in cardiogenic shock.

AIMS: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is currently one of the most used devices in refractory cardiogenic shock. However, there is a lack of evidence on how to set the 'optimal' flow. We aimed to describe the evolution of VA-ECMO flows in a cardiogenic shock population and determine the risk factors of 'high-ECMO flow'. METHODS AND RESULTS: A 7 year database of patients supported with VA-ECMO was used. Based on the median flow during the first 48 h of the VA-ECMO run, patients were classified as 'high-flow' or 'low-flow', respectively, when median ECMO flow was ≥3.6 or <3.6 L/min. Outcomes included rates of ventilator-associated pneumonia, ECMO-related complications, days on ECMO, days on mechanical ventilation, intensive care unit and hospitalization lengths of stay, and in-hospital and 60 day mortality. Risk factors of high-ECMO flow were assessed using univariate and multivariate cox regression. The study population included 209 patients on VA-ECMO, median age was 51 (40-59) years, and 78% were males. The most frequent aetiology leading to cardiogenic shock was end-stage dilated cardiomyopathy (57%), followed by acute myocardial infarction (23%) and fulminant myocarditis (17%). Among the 209 patients, 105 (50%) were classified as 'high-flow'. This group had a higher rate of ischaemic aetiology (16% vs. 30%, P = 0.023) and was sicker at admission, in terms of worse Simplified Acute Physiology Score II score [40 (26-58) vs. 56 (42-74), P < 0.001], higher lactate [3.6 (2.2-5.8) mmol/L vs. 5.2 (3-9.7) mmol/L, P < 0.001], and higher aspartate aminotransferase [97 (41-375) U/L vs. 309 (85-939) U/L, P < 0.001], among others. The 'low-flow' group had less ventilator-associated pneumonia (40% vs. 59%, P = 0.007) and less days on mechanical ventilation [4 (1.5-7.5) vs. 6 (3-12) days, P = 0.009]. No differences were found in lengths of stay or survival according to the ECMO flow. The multivariate analysis showed that risk factors independently associated with 'high-flow' were mechanical ventilation at cannulation [odds ratio (OR) 3.9, 95% confidence interval (CI) 2.1-7.1] and pre-ECMO lactate (OR 1.1, 95% CI 1.0-1.2). CONCLUSIONS: In patients with refractory cardiogenic shock supported with VA-ECMO, sicker patients had higher support since early phases, presenting thereafter higher rates of ventilator-associated pneumonia but similar survival compared with patients with lower flows.

Coronary angiography in patients without ST-segment elevation following out-of-hospital cardiac arrest. COUPE clinical trial.

INTRODUCTION AND OBJECTIVES: The role of emergency coronary angiography (CAG) and percutaneous coronary intervention (PCI) following out-of-hospital cardiac arrest (OHCA) in patients without ST-segment elevation myocardial infarction (STEMI) remains unclear. We aimed to assess whether emergency CAG and PCI would improve survival with good neurological outcome in this population. METHODS: In this multicenter, randomized, open-label, investigator-initiated clinical trial, we randomly assigned 69 survivors of OHCA without STEMI to undergo immediate CAG or deferred CAG. The primary efficacy endpoint was a composite of in-hospital survival free of severe dependence. The safety endpoint was a composite of major adverse cardiac events including death, reinfarction, bleeding, and ventricular arrhythmias. RESULTS: A total of 66 patients were included in the primary analysis (95.7%). In-hospital survival was 62.5% in the immediate CAG group and 58.8% in the delayed CAG group (HR, 0.96; 95%CI, 0.45-2.09; P=.93). In-hospital survival free of severe dependence was 59.4% in the immediate CAG group and 52.9% in the delayed CAG group (HR, 1.29; 95%CI, 0.60-2.73; P=.4986). No differences were found in the secondary endpoints except for the incidence of acute kidney failure, which was more frequent in the immediate CAG group (15.6% vs 0%, P=.002) and infections, which were higher in the delayed CAG group (46.9% vs 73.5%, P=.003). CONCLUSIONS: In this underpowered randomized trial involving patients resuscitated after OHCA without STEMI, immediate CAG provided no benefit in terms of survival without neurological impairment compared with delayed CAG. CLINICALTRIALS: gov Identifier: NCT02641626.

Performance analysis of a STEMI network: prognostic impact of the type of first medical contact facility.

INTRODUCTION AND OBJECTIVES: Prognosis in ST-elevation myocardial infarction (STEMI) is determined by delay in primary percutaneous coronary intervention (PPCI). The impact of first medical contact (FMC) facility type on reperfusion delays and mortality remains controversial. METHODS: We performed a prospective registry of primary coronary intervention (PCI)-treated STEMI patients (2010-2020) in the Codi Infart STEMI network. We analyzed 1-year all-cause mortality depending on the FMC facility type: emergency medical service (EMS), community hospital (CH), PCI hospital (PCI-H), or primary care center (PCC). RESULTS: We included 18 332 patients (EMS 34.3%; CH 33.5%; PCI-H 12.3%; PCC 20.0%). Patients with Killip-Kimball classes III-IV were: EMS 8.43%, CH 5.54%, PCI-H 7.51%, PCC 3.76% (P <.001). All comorbidities and first medical assistance complications were more frequent in the EMS and PCI-H groups (P <.05) and were less frequent in the PCC group (P <.05 for most variables). The PCI-H group had the shortest FMC-to-PCI delay (median 82 minutes); the EMS group achieved the shortest total ischemic time (median 151 minutes); CH had the longest reperfusion delays (P <.001). In an adjusted logistic regression model, the PCI-H and CH groups were associated with higher 1-year mortality, OR, 1.22 (95%CI, 1.00-1.48; P=.048), and OR, 1.17 (95%CI 1.02-1.36; P=.030), respectively, while the PCC group was associated with lower 1-year mortality than the EMS group, OR, 0.71 (95%CI 0.58-0.86; P <.001). CONCLUSIONS: FMC with PCI-H and CH was associated with higher adjusted 1-year mortality than FMC with EMS. The PCC group had a much lower intrinsic risk and was associated with better outcomes despite longer revascularization delays.

Fulminant myocarditis in adults: a narrative review.

Fulminant myocarditis (FM) is an uncommon syndrome characterized by sudden and severe hemodynamic compromise secondary to acute myocardial inflammation, often presenting as profound cardiogenic shock, life-threatening ventricular arrhythmias and/or electrical storm. FM may be refractory to conventional therapies and require mechanical circulatory support (MCS). The immune system has been recognized as playing a pivotal role in the pathophysiology of myocarditis, leading to an increased focus on immunosuppressive treatment strategies. Recent data have highlighted not only the fact that FM has significantly worse outcomes than non-FM, but that prognosis and management strategies of FM are heavily dependent on histological subtype, placing greater emphasis on the role of endomyocardial biopsy in diagnosis. The impact of subtype on severity and prognosis will likewise influence how aggressively the myocarditis is managed, including whether MCS is warranted. Many patients with refractory cardiogenic shock secondary to FM end up requiring MCS, with venoarterial extracorporeal membrane oxygenation demonstrating favorable survival rates, particularly when initiated prior to the development of multiorgan failure. Among the challenges facing the field are the need to more precisely identify immunopathophysiological pathways in order to develop targeted therapies, and the need to better optimize the timing and management of MCS to minimize complications and maximize outcomes.

"Impact of age on management and prognosis of resuscitated sudden cardiac death patients".

Background: Sudden cardiac death (SCD) has a great impact on healthcare due to cardiologic and neurological complications. Admissions of elderly people in Cardiology Intensive Care Units have increased. We assessed the impact of age in presentation, therapeutic management and in vital and neurological prognosis of SCD patients. Methods: We carried out a retrospective, observational, multicenter registry of patients who were admitted with a SCD in 5 tertiary hospitals from January 2013 to December 2020. We divided our cohort into two groups (patients < 80 years and ≥ 80 years). Clinical, analytical and hemodynamic variables as well as in-hospital management were registered and compared between groups. The degree of neurological dysfunction, vital status at discharge and the influence of age on them were also reviewed. Results: We reviewed 1160 patients admitted with a SCD. 11.3% were ≥ 80 years. Use of new antiplatelet agents, performance of a coronary angiography, use of pulmonary artery catheter and temperature control were less carried out in the elderly. Age, non-shockable rhythm, Killip class > 1 at admission, time to CPR initiation > 5 min, time to ROSC > 20 min and lactate > 2 mmol/L were independent predictors for in-hospital mortality. Non-shockable rhythm, Killip class > 1 at admission, time to CPR initiation > 5 min and time to ROSC > 20 min but not age were independent predictors for poor neurological outcomes. Conclusions: Age determined a less aggressive management and it was associated with a worse vital prognosis in patients admitted with a SCD. Nevertheless, age was not associated with worse neurological outcomes.

Circulating virome and inflammatory proteome in patients with ST-elevation myocardial infarction and primary ventricular fibrillation.

Primary ventricular fibrillation (PVF) is a life-threatening complication of ST-segment elevation myocardial infarction (STEMI). It is unclear what roles viral infection and/or systemic inflammation may play as underlying triggers of PVF, as a second hit in the context of acute ischaemia. Here we aimed to evaluate whether the circulating virome and inflammatory proteome were associated with PVF development in patients with STEMI. Blood samples were obtained from non-PVF and PVF STEMI patients at the time of primary PCI, and from non-STEMI healthy controls. The virome profile was analysed using VirCapSeq-VERT (Virome Capture Sequencing Platform for Vertebrate Viruses), a sequencing platform targeting viral taxa of 342,438 representative sequences, spanning all virus sequence records. The inflammatory proteome was explored with the Olink inflammation panel, using the Proximity Extension Assay technology. After analysing all viral taxa known to infect vertebrates, including humans, we found that non-PVF and PVF patients only significantly differed in the frequencies of viruses in the Gamma-herpesvirinae and Anelloviridae families. In particular, most showed a significantly higher relative frequency in non-PVF STEMI controls. Analysis of systemic inflammation revealed no significant differences between the inflammatory profiles of non-PVF and PVF STEMI patients. Inflammatory proteins associated with cell adhesion, chemotaxis, cellular response to cytokine stimulus, and cell activation proteins involved in immune response (IL6, IL8 CXCL-11, CCL-11, MCP3, MCP4, and ENRAGE) were significantly higher in STEMI patients than non-STEMI controls. CDCP1 and IL18-R1 were significantly higher in PVF patients compared to healthy subjects, but not compared to non-PVF patients. The circulating virome and systemic inflammation were not associated with increased risk of PVF development in acute STEMI. Accordingly, novel strategies are needed to elucidate putative triggers of PVF in the setting of acute ischaemia, in order to reduce STEMI-driven sudden death burden.

Non-STEMI vs. STEMI Cardiogenic Shock: Clinical Profile and Long-Term Outcomes.

Cardiogenic shock (CS) is a severe complication of acute myocardial infarction (AMI). In AMI-CS, the ST segment deviation on ECG may be elevated (STEMI-CS) or non-elevated (NSTEMI-CS), which may influence prognosis. Our aim was to analyze the clinical profile, acute-phase prognosis, and long-term outcomes of CS relative to the ST pattern on admission. In a prospective registry of 4647 AMI patients admitted to the intensive cardiac care unit of a university hospital between 2010 and 2019, we compared the clinical characteristics, 30-days case fatality, and long-term outcomes of AMI-CS, based on the presence of ST-segment deviation. AMI-CS developed in 239 (5.1%) patients (26.4% women): 190 (79.5%) STEMI-CS and 49 (20.5%) NSTEMI-CS. The mean age was 69.7 years. The STEMI-CS patients had larger infarcts and more mechanical complications than the NSTEMI-CS patients. The NSTEMI-CS patients had a greater prevalence of hypertension, diabetes, peripheral vascular disease, previous cardiovascular comorbidities, three-vessel disease, and left main disease than the STEMI-CS patients. The STEMI-CS patients had higher 30-day mortality than the NSTEMI-CS (59.5% vs. 36.7%; p = 0.004), even after multivariable adjustment (HR 1.91; 95% CI 1.16-3.14), but no differences in mortality were observed at 3 years. In conclusion, the 30-day case-fatality is higher in STEMI-CS, but the long-term outcome is similar in both groups.

Circulating linoleic acid at the time of myocardial infarction and risk of primary ventricular fibrillation.

Primary ventricular fibrillation (PVF) is a major driver of cardiac arrest in the acute phase of ST-segment elevation myocardial infarction (STEMI). Enrichment of cardiomyocyte plasma membranes with dietary polyunsaturated fatty acids (PUFA) reduces vulnerability to PVF experimentally, but clinical data are scarce. PUFA status in serum phospholipids is a valid surrogate biomarker of PUFA status in cardiomyocytes within a wide range of dietary PUFA. In this nested case-control study (n = 58 cases of STEMI-driven PVF, n = 116 control non-PVF STEMI patients matched for age, sex, smoking status, dyslipidemia, diabetes mellitus and hypertension) we determined fatty acids in serum phospholipids by gas-chromatography, and assessed differences between cases and controls, applying the Benjamini-Hochberg procedure on nominal P-values to control the false discovery rate (FDR). Significant differences between cases and controls were restricted to linoleic acid (LA), with PVF patients showing a lower level (nominal P = 0.002; FDR-corrected P = 0.027). In a conditional logistic regression model, each one standard deviation increase in the proportion of LA was related to a 42% lower prevalence of PVF (odds ratio = 0.58; 95% confidence interval, 0.37, 0.90; P = 0.02). The association lasted after the inclusion of confounders. Thus, regular consumption of LA-rich foods (nuts, oils from seeds) may protect against ischemia-driven malignant arrhythmias.

Awake venoarterial extracorporeal membrane oxygenation for refractory cardiogenic shock.

BACKGROUND: Venoarterial-extracorporeal membrane oxygenation (VA-ECMO) is currently one of the first-line therapies for refractory cardiogenic shock (CS), but its applicability is undermined by the high morbidity associated with its complications, especially those related to mechanical ventilation (MV). We aimed to assess the prognostic impact of keeping patients in refractory CS awake at cannulation and during the VA-ECMO run. METHODS: A 7-year database of patients given peripheral VA-ECMO support was used to conduct a propensity-score (PS)-matched analysis to balance their clinical profiles. Patients were classified as 'awake ECMO' or 'non-awake ECMO', respectively, if invasive MV was used during ≤50% or >50% of the VA-ECMO run. Primary outcomes included ventilator-associated pneumonia and ECMO-related complication rates, and secondary outcomes were 60-day and 1-year mortality. A multivariate logistic-regression analysis was used to identify whether MV at cannulation was independently associated with 60-day mortality. RESULTS: Among 231 patients included, 91 (39%) were 'awake' and 140 (61%) 'non-awake'. After PS-matching adjustment, the 'awake ECMO' group had significantly lower rates of pneumonia (35% vs. 59%, P = 0.017), tracheostomy, renal replacement therapy, and less antibiotic and sedative consumption. This strategy was also associated with reduced 60-day (20% vs. 41%, P = 0.018) and 1-year mortality rates (31% vs. 54%, P = 0.021) compared to the 'non-awake' group, respectively. Lastly, MV at ECMO cannulation was independently associated with 60-day mortality. CONCLUSION: An 'awake ECMO' management in VA-ECMO-supported CS patients is feasible, safe, and associated with improved short- and long-term outcomes.

Circulating Omega-3 Fatty Acids and Incident Adverse Events in Patients With Acute Myocardial Infarction.

BACKGROUND: Dietary omega-3 eicosapentaenoic acid (EPA) has multiple cardioprotective properties. The proportion of EPA in serum phosphatidylcholine (PC) mirrors dietary EPA intake during previous weeks. Circulating EPA in ST-segment elevation myocardial infarction (STEMI) relates to smaller infarct size and preserved long-term ventricular function. OBJECTIVES: The authors investigated whether serum-PC EPA (proxy for marine omega-3 consumption) levels at the time of STEMI were associated with a lower incidence of major adverse cardiovascular events (MACE), all-cause mortality, and readmission for cardiovascular (CV) causes at 3 years' follow-up. We also explored the association of alpha-linolenic acid (ALA, proxy for vegetable omega-3 intake) with all-cause mortality and MACE. METHODS: The authors prospectively included 944 consecutive patients with STEMI (mean age 61 years, 209 women) undergoing primary percutaneous coronary intervention. We determined serum-PC fatty acids with gas chromatography. RESULTS: During follow-up, 211 patients had MACE, 108 died, and 130 were readmitted for CV causes. A Cox proportional hazards model adjusted for known clinical predictors showed that serum-PC EPA at the time of STEMI was inversely associated with both incident MACE and CV readmission (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.62 to 0.94, and HR: 0.74; 95% CI: 0.58 to 0.95, respectively, for a 1-standard deviation [SD] increase). Serum-PC ALA was inversely related to all-cause mortality (HR: 0.65; 95% CI: 0.44 to 0.96, for a 1-SD increase). CONCLUSIONS: Elevated serum-PC EPA and ALA levels at the time of STEMI were associated with a lower risk of clinical adverse events. Consumption of foods rich in these fatty acids might improve the prognosis of STEMI.

Destination Therapy with Left Ventricular Assist Devices in Non-transplant Centres: The Time is Right.

For almost half a century, cardiac transplant has been the only long-term treatment for patients with end-stage heart failure. Implantable left ventricular assist devices (LVADs) have emerged as a new treatment option for advanced heart failure as destination therapy for patients either too old or not suitable for transplant. A meta-analysis presenting head-to-head comparisons of cardiac transplant versus LVAD as destination therapy (LVAD-DT) found no difference in 1-year mortality rates between LVAD-DT and cardiac transplant (OR 1.49; 95% CI [0.48-4.66]; I2=82.8%). Moreover, a recent subanalysis from the Interagency Registry for Mechanically Assisted Circulatory Support found similar outcomes after LVAD-DT implantation in both transplant and non-transplant centres. The time is right for LVAD-DT in non-transplant centres, provided multidisciplinary heart failure teams and expertise are in place.