Effect of COMBinAtion therapy with remote ischemic conditioning and exenatide on the Myocardial Infarct size: a two-by-two factorial randomized trial (COMBAT-MI).

Remote ischemic conditioning (RIC) and the GLP-1 analog exenatide activate different cardioprotective pathways and may have additive effects on infarct size (IS). Here, we aimed to assess the efficacy of RIC as compared with sham procedure, and of exenatide, as compared with placebo, and the interaction between both, to reduce IS in humans. We designed a two-by-two factorial, randomized controlled, blinded, multicenter, clinical trial. Patients with ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention (PPCI) within 6 h of symptoms were randomized to RIC or sham procedure and exenatide or matching placebo. The primary outcome was IS measured by late gadolinium enhancement in cardiac magnetic resonance performed 3-7 days after PPCI. The secondary outcomes were myocardial salvage index, transmurality index, left ventricular ejection fraction and relative microvascular obstruction volume. A total of 378 patients were randomly allocated, and after applying exclusion criteria, 222 patients were available for analysis. There were no significant interactions between the two randomization factors on the primary or secondary outcomes. IS was similar between groups for the RIC (24 ± 11.8% in the RIC group vs 23.7 ± 10.9% in the sham group, P = 0.827) and the exenatide hypotheses (25.1 ± 11.5% in the exenatide group vs 22.5 ± 10.9% in the placebo group, P = 0.092). There were no effects with either RIC or exenatide on the secondary outcomes. Unexpected adverse events or side effects of RIC and exenatide were not observed. In conclusion, neither RIC nor exenatide, or its combination, were able to reduce IS in STEMI patients when administered as an adjunct to PPCI.

Clinical picture, management and risk stratification in patients with cardiogenic shock: does gender matter?

BACKGROUND: Early recognition and risk stratification are crucial in cardiogenic shock (CS). A lower adherence to recommendations has been described in women with cardiovascular diseases. Little information exists about disparities in clinical picture, management and performance of risk stratification tools according to gender in patients with CS. METHODS: Data from the multicenter Red-Shock registry were used. All consecutive patients with CS were included. Both CardShock and IABP-SHOCK II risk scores were calculated. The primary end-point was in-hospital mortality. The discriminative ability of both scores according to gender was assessed by binary logistic regression, calculating Receiver operating characteristic (ROC) curves and the corresponding area under the curve (AUC). RESULTS: A total of 793 patients were included, of whom 222 (28%) were female. Women were significantly older and had a lower proportion of chronic obstructive pulmonary disease and prior myocardial infarction. CS was less often related to acute coronary syndromes (ACS) in women. The use of vasoactive drugs, renal replacement therapy, invasive ventilation, therapeutic hypothermia and mechanical circulatory support was similar between both groups. In-hospital mortality was 346/793 (43.6%). Mortality was not significantly different according to gender (p = 0.194). Cardshock risk score showed a good ability for predicting in-hospital mortality both in man (AUC 0.69) and women (AUC 0.735). Likewise, the IABP-II successfully predicted in-hospital mortality in both groups (man: AUC 0.693; women: AUC 0.722). CONCLUSIONS: No significant differences were observed regarding management and in-hospital mortality according to gender. Both the CardShock and IABP-II risk scores depicted a good ability for predicting mortality also in women with CS.

Corrigendum: Dynamics of Emergency Cardiovascular Hospital Admissions and In-Hospital Mortality During the COVID-19 Pandemic: Time Series Analysis and Impact of Socioeconomic Factors.

[This corrects the article DOI: 10.3389/fcvm.2022.827212.].

Dynamics of Emergency Cardiovascular Hospital Admissions and In-Hospital Mortality During the COVID-19 Pandemic: Time Series Analysis and Impact of Socioeconomic Factors.

Aims: This study aimed to evaluate the decline in urgent cardiovascular hospital admissions and in-hospital mortality during the COVID pandemic in two successive waves, and to evaluate differences by sex, age, and deprivation index subgroups. Methods and Results: We obtained acute cardiovascular hospital episodes during the years 2019-2020 from region-wide data on public healthcare usage for the population of Catalonia (North-East Spain). We fitted time models to estimate the incidence rate ratios (IRRs) of the acute coronary syndrome (ACS) and acute heart failure (HF) admissions during the first pandemic wave, the between-waves period, and the second wave compared with the corresponding pre-COVID-19 periods and to test for the interaction with sex, age, and area-based socioeconomic level. We evaluated the effect of COVID-19 period on in-hospital mortality. ACS (n = 8,636) and HF (n = 27,566) episodes were defined using primary diagnostic ICD-10 codes. ACS and HF admissions decreased during the first wave (IRR = 0.66, 95%CI: 0.58-0.76 and IRR = 0.61, 95% CI: 0.55-0.68, respectively) and during the second wave (IRR = 0.80, 95%CI: 0.72-0.88 and IRR = 0.76, 95%CI: 0.69-0.84, respectively); acute HF admissions also decreased in the period between waves (IRR: 0.81, 95%CI: 0.74-0.89). The impact was similar in all sex and socioeconomic subgroups and was higher in older patients with ACS. In-hospital mortality was higher than expected only during the first wave. Conclusion: During the first wave of the COVID-19 pandemic, there was a marked decline in urgent cardiovascular hospital admissions that were attenuated during the second wave. Both the decline and the attenuation of the effect have been similar in all subgroups regardless of age, sex, or socioeconomic status. In-hospital mortality for ACS and HF episodes increased during the first wave, but not during the second wave.

Emergent Percutaneous Closure of a Free-Wall Perforation During Impella Implantation.

Free wall perforation during percutaneous manipulation of devices and wires into the ventricular cavities is an uncommon but life-threatening complication that should be managed with emergent surgery whenever possible. However, the number of patients with prohibitive surgical risk that undergo complex percutaneous cardiac procedures is increasing. Some cases of ventricle perforation during Impella® (Abiomed; Danvers, MA) implantation have been previously reported but in all previous reported cases the patient underwent emergent surgery. We present a case of iatrogenic perforation during Impella® implantation that was emergently treated using an Amplatzer® Duct Occluder II device (Abbott Vascular; Santa Clara, CA).

Diabetes mellitus is not independently associated with mortality in elderly patients with ST-segment elevation myocardial infarction. Insights from the Codi Infart registry.

BACKGROUND: Diabetes mellitus predicts poorer outcomes in patients with acute coronary syndrome (ACS), but the magnitude of this association in patients at older ages remains controversial. METHODS: Data were extracted from the Codi Infart database. All consecutive patients with diagnosis of ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) between 2010 and 2015 were included. We assessed the impact of diabetes mellitus on 30-day and one-year mortality in patients aged less than and at least 75 years. RESULTS: A total of 12 792 cases were registered, of whom 3023 (23.6%) were aged at least 75 years. About 20% patients had previous diabetes mellitus diagnosis. Patients aged at least 75 years had higher prevalence of comorbidities, higher proportion of heart failure at admission, a more extensive coronary artery disease and significant delay to reperfusion (P < 0.001). Diabetes mellitus was associated with higher 30-day mortality both in young [odds ratio (OR) 1.97, 95% confidence interval (CI): 1.43-2.70] and in elderly patients (OR 1.43, 95% CI: 1.07-1.91). After adjusting for potential confounders, this association remained significant in young patients (OR 1.47, 95% CI: 1.00-2.16, P = 0.047), but not in the elderly (OR 1.14, P = 0.43). Likewise, a crude association between diabetes mellitus and one-year mortality was observed in both groups (young patients: HR = 1.93; 95% CI: 1.51-2.46; older patients: HR = 1.33; 95% CI: 1.08-1.64). However, after adjusting for potential confounders, this association remained significant in younger patients (HR = 1.46; 95% CI: 1.13-1.89; P < 0.001), but not in the elderly (HR = 1.16; P = 0.17). CONCLUSION: A significant proportion of these nonselected patients with STEMI had previous diabetes mellitus. The association between diabetes mellitus and outcomes is different according to age.

High incidence of TIMI flow 0 to I in patients with ST-elevation myocardial infarction without electrocardiographic lytic criteria.

BACKGROUND: Most patients with ST-elevation myocardial infarction fulfilling ST-segment elevation (STE) lytic criteria present an occluded culprit artery but the occlusion rate in those with minimal STE (minSTE) not fulfilling lytic criteria is unknown. METHODS: In 63 patients with minSTE (mean STE:1.2 +/- 0.6 mm) and 149 with lytic STE criteria (lyticSTE, 4.8 +/- 3.1 mm), an emergency coronary angiography was performed, serial creatine kinase-MB was determined, and ejection fraction was measured by 2-dimensional echocardiography. RESULTS: The 2 groups showed similar time from pain onset to electrocardiogram (minSTE 196 +/- 199 vs lyticSTE, 176 +/- 172 min, P = .444), and although time to catheterization was longer in patients with minSTE (426 +/- 314 vs 253 +/- 239 min, P < .001), the rate of TIMI flow 0 to I (88% vs 81%, P = .21) was similar and percutaneous coronary intervention was performed in >80% of patients from the 2 groups. Moreover, patients with minSTE had higher rate of collateral circulation (27% vs 13%, P = .013), lower rate of Q waves (44% vs 60%, P = .041), lower creatine kinase-MB (202 +/- 150 vs 335 +/- 280, microg/L, P < .001), higher ejection fraction (54% +/- 9% vs 49% +/- 12%, P = .004), and lower mortality (0% vs 7.4%, P = .036). CONCLUSIONS: ST-elevation myocardial infarction patients with minSTE present a high prevalence of TIMI flow 0 to I similar to those meeting lyticSTE suggesting an identical underlying mechanism and the potential to benefit from primary angioplasty.

Use of perampanel in one case of super-refractory hypoxic myoclonic status: Case report.

UNLABELLED: Proper treatment of hypoxic myoclonic status is not clearly determined. Induced hypothermia is improving prognosis and a more aggressive treatment might be beneficial in some patients. Among the new options of antiepileptic drugs, perampanel (PER) is a drug with a novel mechanism, and it might be a promising drug for myoclonic status or as an antimyoclonic drug. We describe the use of PER in one patient with hypoxic super-refractory myoclonic status. DESCRIPTION: A 51-year-old patient presented after an out-of-hospital cardiac arrest due to an acute myocardial infarction. The patient was diagnosed with clinical and electrical (EEG) myoclonic status at the rewarming phase. Several treatments were used, starting with clonazepam, valproate, sedation (midazolam, propofol), and subsequently barbiturate-induced coma with persistent myoclonic status. Finally, we decided to try PER (dose: 6-8 mg) through a nasogastric tube, resulting in a marked improvement of EEG activity and myoclonus decrease. The patient had a progressive clinical improvement, with a CPC (Cerebral Performance Category) scale score of 1. CONCLUSION: This case shows the potential utility of PER as a therapeutic option in super-refractory hypoxic status and even its potential use before other aggressive alternatives considering their greater morbidity.

Typical angina without significant coronary stenosis: comparison of clinical profile, circadian presentation, and long-term follow-up between patients with and patients without vasospastic angina.

OBJECTIVES: The spectrum of patients with 'angina and normal coronary arteries' ranges from severe vasospasm to atypical chest pain. Among those with typical angina, however, little is known about similarities in the clinical profile and circadian presentation between typical nonvasospastic angina and normal coronary arteries (tANCA) and vasospastic angina (VA). MATERIALS AND METHODS: Clinical, ECG, and angiographic features as well as the circadian characteristics of angina were compared between 384 tANCA and 273 VA patients. Follow-up events were also analyzed. RESULTS: tANCA patients had greater female predominance (61 vs. 18%), higher incidence of dyspnea to moderate exertion (49 vs. 12%), lower incidence of tobacco smoking (25 vs. 67%), but a similar low rate of diabetes (8.9 vs. 4.4%). In both groups, however, dyspnea and smoking were associated with female and male sex, respectively. tANCA patients showed lower but non-negligible frequency of early morning (25 vs. 67%) and evening angina (37 vs. 54%), similar rate of nocturnal angina (47 vs. 50%), and higher rate of emotional angina (49 vs. 31%). Moreover, a high proportion of patients gained pain relief with nitroglycerin (97% in VA, 246/253, and 76% in tANCA, 231/306). At 140 months, frequent angina (>10 episodes/year) was rare (VA: 7.1% vs. tANCA: 6.3%) as was the rate of cardiac death/myocardial infarction (7.3 vs. 6.0%, P=0.524). CONCLUSION: Despite differences in the clinical profile between VA and tANCA patients, there is notable sharing of circadian presentation of rest angina, response to nitroglycerin, and long-term presence and frequency of angina that suggests more similarities in underlying mechanisms than heretofore suspected.

Lower tissue factor inhibition in patients with ST segment elevation than in patients with non ST elevation acute myocardial infarction.

INTRODUCTION: Mechanisms to explain the different course of coronary thrombosis between ST elevation myocardial infarction (STEMI) and non-STEMI patients remain poorly defined. We hypothesize, however, that STEMI patients may present lower tissue factor plasma inhibition to partly account for their more persistent coronary thrombotic occlusion. MATERIALS AND METHODS: Total (t-TFPI ) and free tissue factor plasma inhibitor (f-TFPI), thrombin-antithrombin complex (TAT), plasminogen activator inhibitor 1 (PAI-1), von Willebrand factor (vWF), and fibrinogen were measured on admission and at 3 and 6 months in patients with a first STEMI (n:69) or non-STEMI (n:60). C reactive protein (CRP) was also measured on admission and at 3 months. RESULTS: STEMI patients showed lower admission levels of t-TFPI (p=0.001), f-TFPI (p=0.030) and fibrinogen (p=0.022), and higher vWF levels (p=0.005) than non-STEMI whereas TAT, PAI and CRP levels were comparable. At 3 and 6 months VWF, t-TFPI, f-TFPI, and TAT levels declined significantly in the 2 groups (p=0.002) reaching similar values. CRP levels also declined at 3 months (p=0.002). Moreover, the rate of cardiac mortality, non fatal MI or stroke during a 6 year follow-up were unrelated to admission coagulation parameters. CONCLUSIONS: The lower inhibition of tissue factor and greater endothelial dysfunction in STEMI than in non-STEMI patients may enhance thrombosis at the culprit lesion and adjacent coronary plaques, and hence, account at least in part for their different pathophysiology. This condition, however, is limited to the acute phase.

Acute cardiac syndromes without significant coronary stenosis: differential features between myocardial infarction and apical-ballooning syndrome.

OBJECTIVE: Among patients with acute cardiac syndromes without coronary stenosis, the clinical, electrocardiographic, echocardiographic, and angiographic features of those with a first acute myocardial infarction (AMI) were compared with those with apical-ballooning syndrome (ABS). METHODS: Data of consecutive patients admitted with a first AMI (n=30) or ABS (n=45) were reviewed. RESULTS: Patients with ABS were older (72 vs. 56 years; P=0.001) and presented a higher frequency of female sex (91 vs. 43%; P=0.001), triggering emotional or physical stress (47 vs. 17%; P=0.003) and a lower rate of tobacco smoking (27 vs. 50%; P=0.051) than those with the first AMI. They also presented a greater number of leads (5.5 vs. 3.6; P=0.01) and more anterior or anterior+inferior involvement (96 vs. 40%; P<0.001), more depressed ejection fraction (45 vs. 57%; P=0.001), more proportion of akinesia or diskinesia (89 vs. 27%; P=0.001) that extended beyond the boundaries of a single-vessel territory, and a greater rate of left ventricular outflow obstruction (29 vs. 0%; P=0.001) and heart failure (38 vs. 10%; P=0.015). Frequency of nonsignificant coronary stenosis or smooth vessels, however, was similar in both groups. CONCLUSION: Patients with ABS were older and more frequently were women than those with first AMI without significant coronary stenosis and had larger hypocontractile areas. The preponderance of tobacco smoking, pain without triggers, and hypocontractility limited to one-vessel territory in the latter, however, may suggest a transient thrombotic/vasospastic event as their underlying mechanism as opposed to patients with ABS.

Platelets activated by transient coronary occlusion exacerbate ischemia-reperfusion injury in rat hearts.

Platelets (Plt) accumulate in reperfused myocardium but their effect on myocardial necrosis has not been established. We tested the hypothesis that the effect of Plt depends on their activation status. Pig Plt were obtained before 48 min of coronary occlusion (pre-CO-Plt), 10 min after reperfusion (R-Plt), or after a 60-min sham operation (sham-Plt). Plt were infused into isolated rat hearts (n = 124) and subsequently submitted to 60 min of ischemia and 60 min of reperfusion. P-selectin expression was higher (P = 0.02) in R-Plt than in pre-CO-Plt or sham-Plt. Lactate dehydrogenase (LDH) release during reperfusion was similar in hearts receiving pre-CO-Plt, sham-Plt, or no Plt, but R-Plt increased LDH release by 60% (P = 0.004). Activation of pre-CO-Plt with thrombin increased P-selectin expression and LDH release (P < 0.001), and these results were unaffected by tirofiban. There was a close correlation between P-selectin expression and LDH release (r = 0.84; P < 0.001), and myocardial Plt accumulation (r = 0.85; P < 0.001). We conclude that the deleterious effect of Plt on reperfused myocardium depends on their activation status as represented by P-selectin expression, which is enhanced by ischemia-reperfusion.