Has hyperglycemia a different prognostic role in STEMI patients with or without diabetes?

BACKGROUND AND AIMS: Hyperglycemia at hospital admission is a common finding in patients with STEMI. However, whether elevated acute glycemia in these patients may have a direct impact on worsening prognosis or is just a marker of a greater neurohormonal activation in response to the infarction is still unsettled. We sought to investigate the prognostic impact of hyperglycemia at hospital admission in patients undergoing primary PCI (pPCI) for STEMI, and the influence of the presence of diabetes mellitus (DM) on its prognostic impact. METHODS: and Results, We enrolled 2958 consecutive STEMI patients treated by pPCI. Hyperglycemia was defined as plasma glucose >198 mg/dL (or >11 mmol/L). Patients with hyperglycemia showed a greater risk-profile; they also experienced a higher mortality both at univariable (17.6% vs 5.2%, p < 0.001) and multivariable (HR 1.9, 95%IC 1.5-2.9, p = 0.001) analysis. However, after stratification for DM presence, hyperglycemia resulted as an independent predictor of mortality only in patients without DM (HR 2, 95%IC 1.2-3.4, p = 0.01). CONCLUSION: Hyperglycemia in the setting of myocardial infarction treated with primary PCI in an independent predictor of all-cause mortality in patients without diabetes; in patients with diabetes, its prognostic impact seems attenuated.

Leptin affects the inflammatory response after STEMI.

Leptin is an adipose tissue-derived hormone primarily involved in the regulation of food intake. Leptine has been shown to have a much broader role than just regulating body weight and appetite in response to food intake: among the others, it has been associated with increased ROS production and inflammation, factors involved in the restoration of an effective myocardial reperfusion after myocardial revascularization. Our study, to our best knowledge, is the first showing a direct relationship between leptin serum levels, inflammatory mediators of the ischemia reperfusion damage and effective myocardial reperfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Our findings suggest that leptin serum levels are directly associated with the inflammatory response during an acute myocardial infarction and may have a role in risk stratification in this clinical setting.

Pretreatment with prasugrel in non-ST-segment elevation acute coronary syndromes.

BACKGROUND: Although P2Y12 antagonists are effective in patients with non-ST-segment elevation (NSTE) acute coronary syndromes, the effect of the timing of administration--before or after coronary angiography--is not known. We evaluated the effect of administering the P2Y12 antagonist prasugrel at the time of diagnosis versus administering it after the coronary angiography if percutaneous coronary intervention (PCI) was indicated. METHODS: We enrolled 4033 patients with NSTE acute coronary syndromes and a positive troponin level who were scheduled to undergo coronary angiography within 2 to 48 hours after randomization. Patients were randomly assigned to receive prasugrel (a 30-mg loading dose) before the angiography (pretreatment group) or placebo (control group). When PCI was indicated, an additional 30 mg of prasugrel was given in the pretreatment group at the time of PCI and 60 mg of prasugrel was given in the control group. RESULTS: The rate of the primary efficacy end point, a composite of death from cardiovascular causes, myocardial infarction, stroke, urgent revascularization, or glycoprotein IIb/IIIa inhibitor rescue therapy (glycoprotein IIb/IIIa bailout) through day 7, did not differ significantly between the two groups (hazard ratio with pretreatment, 1.02; 95% confidence interval [CI], 0.84 to 1.25; P=0.81). The rate of the key safety end point of all Thrombolysis in Myocardial Infarction (TIMI) major bleeding episodes, whether related or not related to coronary-artery bypass grafting (CABG), through day 7 was increased with pretreatment (hazard ratio, 1.90; 95% CI, 1.19 to 3.02; P=0.006). The rates of TIMI major bleeding and life-threatening bleeding not related to CABG were increased by a factor of 3 and 6, respectively. Pretreatment did not reduce the rate of the primary outcome among patients undergoing PCI (69% of the patients) but increased the rate of TIMI major bleeding at 7 days. All the results were confirmed at 30 days and in prespecified subgroups. CONCLUSIONS: Among patients with NSTE acute coronary syndromes who were scheduled to undergo catheterization, pretreatment with prasugrel did not reduce the rate of major ischemic events up to 30 days but increased the rate of major bleeding complications. (Funded by Daiichi Sankyo and Eli Lilly; ACCOAST ClinicalTrials.gov number, NCT01015287.).

[Venoarterial extracorporeal membrane oxygenation: from evidence to clinical practice]. / Il supporto della circolazione extracorporea nelle emergenze cardiologiche: evidenze scientifiche e pratica clinica.

Mortality for cardiogenic shock is still high despite optimal pharmacological therapy. Therefore, active mechanical circulatory support devices are increasingly used; venoarterial extracorporeal membrane oxygenation (VA-ECMO) enables full circulatory and respiratory support. However, recent data show that in patients with infarct-related shock unselected early use of VA-ECMO does not improve survival and is associated with major bleeding and peripheral ischemic complications. Nowadays, waiting for the results of definitive randomized controlled trials, the main indication for ECMO utilization is in selected patients with cardiac arrest, in those with shock for advanced heart failure refractory to conventional therapy, in those with fulminant myocarditis, in patients candidate for heart transplant or ventricular assistance, especially in presence of respiratory insufficiency and severe biventricular dysfunction. An important recommendation is its utilization in specialized, high-volume centers in the setting of hub and spoke hospitals.

Acute Coronary Syndromes and SARS-CoV-2 Infection: Results From an Observational Multicenter Registry During the Second Pandemic Spread in Lombardy.

Background: COVID-19 had an adverse impact on the management and outcome of acute coronary syndromes (ACS), but most available data refer to March-April 2020. Aim: This study aims to investigate the clinical characteristics, time of treatment, and clinical outcome of patients at hospitals serving as macro-hubs during the second pandemic wave of SARS-CoV-2 (November 2020-January 2021). Methods and Results: Nine out of thirteen "macro-hubs" agreed to participate in the registry with a total of 941 patients included. The median age was 67 years (IQR 58-77) and ST-elevation myocardial infarction (STEMI) was the clinical presentation in 54% of cases. Almost all patients (97%) underwent coronary angiography, with more than 60% of patients transported to a macro-hub by the Emergency Medical Service (EMS). In the whole population of STEMI patients, the median time from symptom onset to First Medical Contact (FMC) was 64 min (IQR 30-180). The median time from FMC to CathLab was 69 min (IQR 39-105). A total of 59 patients (6.3%) presented a concomitant confirmed SARS-CoV-2 infection, and pneumonia was present in 42.4% of these cases. No significant differences were found between STEMI patients with and without SARS-CoV-2 infection in treatment time intervals. Patients with concomitant SARS-CoV-2 infection had a significantly higher in-hospital mortality compared to those without (16.9% vs. 3.6%, P < 0.0001). However, post-discharge mortality was similar to 6-month mortality (4.2% vs. 4.1%, P = 0.98). In the multivariate analysis, SARS-CoV-2 infection did not show an independent association with in-hospital mortality, whereas pneumonia had higher mortality (OR 5.65, P = 0.05). Conclusion: During the second wave of SARS-CoV-2 infection, almost all patients with ACS received coronary angiography for STEMI with an acceptable time delay. Patients with concomitant infection presented a lower in-hospital survival with no difference in post-discharge mortality; infection by itself was not an independent predictor of mortality but pneumonia was.

Clinical governance of patients with acute coronary syndromes.

AIMS: Using the principles of clinical governance, a patient-centred approach intended to promote holistic quality improvement, we designed a prospective, multicentre study in patients with acute coronary syndrome (ACS). We aimed to verify and quantify consecutive inclusion and describe relative and absolute effects of indicators of quality for diagnosis and therapy. METHODS AND RESULTS: Administrative codes for invasive coronary angiography and acute myocardial infarction were used to estimate the ACS universe. The ratio between the number of patients included and the estimated ACS universe was the consecutive index. Co-primary quality indicators were timely reperfusion in patients admitted with ST-elevation ACS and optimal medical therapy at discharge. Cox-proportional hazard models for 1-year death with admission and discharge-specific covariates quantified relative risk reductions and adjusted number needed to treat (NNT) absolute risk reductions. Hospital codes tested had a 99.5% sensitivity to identify ACS universe. We estimated that 7344 (95% CI: 6852-7867) ACS patients were admitted and 5107 were enrolled-i.e. a consecutive index of 69.6% (95% CI 64.9-74.5%), which varied from 30.7 to 79.2% across sites. Timely reperfusion was achieved in 22.4% (95% CI: 20.7-24.1%) of patients, was associated with an adjusted hazard ratio (HR) for 1-year death of 0.60 (95% CI: 0.40-0.89) and an adjusted NNT of 65 (95% CI: 44-250). Corresponding values for optimal medical therapy were 70.1% (95% CI: 68.7-71.4%), HR of 0.50 (95% CI: 0.38-0.66), and NNT of 98 (95% CI: 79-145). CONCLUSION: A comprehensive approach to quality for patients with ACS may promote equitable access of care and inform implementation of health care delivery. REGISTRATION: ClinicalTrials.Gov ID NCT04255537.

BMPR2 mutations and response to inhaled or parenteral prostanoids: a case series.

Whether mutations in the BMPR2 gene may influence the response to PAH-specific therapies has not yet been investigated. In this study, in 13 idiopathic, heritable or anorexigen-associated PAH patients, in whom treatment escalation was performed by adding a prostanoid, a greater haemodynamic improvement was observed in BMPR2-negative than in BMPR2-positive patients.

[Early diagnosis and management of cardiac allograft vasculopathy: is it time for a standardized approach?] / Individuazione precoce e gestione della coronaropatia nel cuore trapiantato: è tempo per una uniformità di approccio?

Cardiac allograft vasculopathy (CAV) still represents the main cause of long-term graft loss after heart transplantation. Its silent clinical presentation makes an early identification difficult, with relevant implications for a standardized follow-up. Although technological advances have provided sophisticated non-invasive techniques for CAV assessment, intravascular ultrasound in conjunction with coronary angiography is still the gold standard to detect rapidly progressive CAV and to provide prognostic information during follow-up. Current guidelines recommend annual coronary angiography during the first 5 years and every 2 years thereafter. Although commonly performed, coronary angiography has multiple limitations, especially in young patients and in case of chronic kidney disease. This article aims to review the literature about the monitoring of CAV and to propose an ideal and individualized pathway for early diagnosis of CAV in transplanted patients, based on their cardiovascular risk.

Risk stratification in patients with residual pulmonary hypertension after pulmonary endarterectomy.

BACKGROUND: Few studies addressed the issue of risk stratification in patients with residual pulmonary hypertension (PH) after pulmonary endarterectomy (PEA). This study tested the potential added value of parameters that have not been included in existing risk models. METHODS: We evaluated 546 consecutive patients with chronic thromboembolic pulmonary hypertension who underwent PEA and were followed-up for a median period of 58 months. RESULTS: Among the 242 with residual PH, 27 died and had 127 a clinical worsening event. At univariable analysis, the parameters associated with poor survival were pulmonary vascular resistance (PVR) ≥425 dyn·s·cm-5 (p ≤ 0.001), mean pulmonary artery pressure (mPAP) ≥38 mmHg (p = 0.003) and pulmonary artery compliance (CPA) ≤1.8 ml/mmHg (p = 0.014). In the bivariable models including either PVR or mPAP as first parameter, the addition of CPA was not statistically significant. The parameters associated with poor clinical worsening were CPA ≤1.8 ml/mmHg (p < 0.001), PVR ≥425 dyn·s·cm-5 (p = 0.002), arterial oxygen tension (PaO2) ≤ 75 mmHg (p = 0.003), mPAP ≥38 mmHg (p = 0.008). In a multivariable analysis which included PVR ≥425 as the first parameter, the addition of both CPA ≤1.8 ml/mmHg and of PaO2 ≤ 75 mmHg significantly improved prognostic stratification (Harrel's C of the model = 0.64, p < 0.001). Noticeably, the lower tertile of the model's predictor index identified a subgroup of 91 patients who had an event rate numerically similar to that of patients without residual PH. CONCLUSIONS: Risk stratification in residual PH can be refined if CPA and PaO2 are considered in association with standard hemodynamic parameters.

Post-ROSC peripheral perfusion index discriminates 30-day survival after out-of-hospital cardiac arrest.

BACKGROUND: Prognostication after an out-of-hospital cardiac arrest (OHCA) remains a challenge. The peripheral-derived perfusion index (PI) is a simple and non-invasive way to assess perfusion. We sought to assess whether the PI was able to discriminate the prognosis of patients resuscitated from an OHCA. METHODS: All the reports generated by the manual monitor/defibrillator (Corpuls 3 by GS Elektromedizinische Geräte G. Stemple GmbH, Germany) used for all the OHCAs who achieved ROSC treated by our Emergency Medical Service from January 2015 to December 2018 were reviewed. The mean PI value of each minute after ROSC was automatically provided by the device and the mean value of 30 min of monitoring (MPI30) was calculated. Pre-hospital data were collected according to the Utstein 2014 recommendations. RESULTS: Among 1,909 resuscitation attempts, ROSC was achieved in 346 and it was possible to calculate an MPI30 in 164. MPI30 was higher in the patients who survived at 30 days [1.6 (95% CI 1.2-2.1) vs 1 (95% CI 0.8-1.3), p = 0.0017]. At the multivariable Cox regression model, after correction for shockable rhythm, witnessed status, bystander CPR, age, and blood pressure, MPI30 was found to be an independent predictor of both 30-day mortality [RR 0.83 (95% CI 0.69-0.99), p = 0.036] and 30-day mortality or poor neurologic outcome [RR 0.85 (95% CI 0.72-0.99), p = 0.04]. Overall 30-day survival with good neurologic outcome was significantly different in the three tertiles [T1: 0.1-0.8; T2: 0.9-1.8 and T3: 1.82-7.8, log-rank p = 0.007]. CONCLUSION: The post-ROSC peripheral perfusion index was found to be an independent predictor of 30-day mortality or poor neurologic outcome. It could help prognostication in OHCA patients.

Long-Term Effects of the Replacement of Calcineurin Inhibitors With Everolimus and Mycophenolate in Patients With Calcineurin Inhibitor-Related Nephrotoxicity.

BACKGROUND: There is little evidence on the long-term effects of calcineurin inhibitor (CNI) withdrawal and substitution with everolimus and mycophenolate mofetil in maintenance therapy of patients who have received heart transplants and have concurrent CNI nephrotoxicity. Aims of this study were to evaluate the progression of renal dysfunction after discontinuation of CNIs and to monitor for major adverse events after therapy change. METHODS: Data from 41 patients who underwent heart transplant and have different degrees of renal dysfunction (estimated glomerular filtration rate [eGFR] <60 mL/min/1.73 m2), without evidence of proteinuria, and in whom CNI therapy was replaced by everolimus, were analyzed. At the time of CNI withdrawal, clinical parameters, echocardiographic data, blood tests of renal function, and monitoring of adverse events were recorded. The median follow-up period was 5 years ± 28 months. RESULTS: In 52% of patients, there was a clear improvement in renal function (10.5 mL/min/1.73 m2 of extra eGFR on average). The former were characterized by less advanced age and a short time from the heart transplant. The echocardiographic parameters showed a significant reduction in septum thickness (11.58 ± 2 mm vs 10.29 ± 2 mm; P = .0001) and in left ventricle posterior wall thickness (10.74 ± 1 mm vs 9.74 ± 1 mm; P = .0004). The incidence of late acute rejection and cardiac allograft vasculopathy was similar in our population compared to literature data. CONCLUSIONS: A therapeutic switch from CNIs to everolimus and mycophenolate mofetil can improve renal function in patients with CNI nephrotoxicity, especially in those with a shorter time period from transplantation, without exposing them to a higher incidence of late acute rejection and cardiac allograft vasculopathy.

Percutaneous Coronary Intervention Techniques for Bifurcation Disease: Network Meta-analysis Reveals Superiority of Double-Kissing Crush.

BACKGROUND: Provisional T-stenting (PS) is generally recommended to treat patients with coronary bifurcation disease (CBD) percutaneously, but PS may not fit all complex bifurcation anatomies. Therefore, several types of up-front 2-stent techniques have been described. We aimed to identify the best percutaneous coronary intervention (PCI) technique to manage patients with CBD. METHODS: We systematically reviewed randomized controlled trials (RCTs) including patients undergoing CBD PCI which included several types of PCI techniques-PS, double-kissing (DK) crush, T-stenting and protrusion, culotte, dedicated bifurcation stents, crushing, and T-stenting-and we compared device-oriented clinical events (DOCEs), a composite of cardiac death, target-vessel myocardial infarction, stent thrombosis, and target-lesion or target-vessel revascularization, in a network meta-analysis. We included 26 RCTs, leading to a pooled population of 10,339 patient-years and a total of 1229 DOCEs. RESULTS: The DK-crush technique was associated with the lowest DOCE rate, with a relative risk of 0.62 (95% CI 0.42-0.92) compared with the PS technique. DK-crush had the highest probability (model likelihood 90.2%, area under the cumulative ranking curve 98.0%) of being the best technique among those explored to reduce DOCEs in patients receiving CBD PCI. CONCLUSIONS: When a 2-stent strategy is considered in a patient with CBD, the DK-crush technique reduces DOCEs compared with other bifurcation techniques based on all available RCTs.

[Is it necessary to prescribe oral anticoagulant therapy for paroxysmal atrial fibrillation during acute coronary syndrome, and for how long?] / È necessario prescrivere, e per quanto tempo, la terapia anticoagulante orale nel paziente con fibrillazione atriale parossistica in corso di sindrome coronarica acuta?

There is limited knowledge on the occurrence of new-onset, transient atrial fibrillation during acute coronary syndromes; compared with patients in sinus rhythm, patients with paroxysmal atrial fibrillation have an increased risk of in-hospital and long-term recurrence of the arrhythmia, all-cause mortality and ischemic stroke. There is a lack of prospective, randomized studies on anticoagulant therapy modalities in this specific subset of patients. In the absence of a widely accepted anticoagulation algorithm, the international guidelines for the management of atrial fibrillation recommend to initiate anticoagulant treatment during acute coronary syndromes estimating in each patient the thrombotic and bleeding risk using the CHA2DS2-VASc and HAS-BLED scores, respectively. In the last updates of the guidelines for the management of atrial fibrillation, non-vitamin K oral anticoagulants are recommended over warfarin and, in patients with atrial fibrillation who have undergone percutaneous coronary intervention with stenting for acute coronary syndromes, dual antiplatelet therapy with rivaroxaban or dabigatran and clopidogrel is reasonable to reduce the risk of bleeding compared with triple therapy. Neither scientific evidences nor recommendations from the guidelines are available about the duration of anticoagulant therapy in case of paroxysmal atrial fibrillation during acute coronary syndromes.

Load distributing band device for mechanical chest compressions: An Utstein-categories based analysis of survival to hospital discharge.

PURPOSE: The role of load distributing band device (LDB, AutoPulse®, Zoll Medical Corporation, Chelmsford, MA, USA) in out-of-hospital cardiac arrest is still a matter of debate, with few studies reaching conflicting results available in literature. We sought to assess whether the use of the LBD device could affect survival to hospital discharge in the different Utstein categories. MATERIALS AND METHODS: All consecutive patients enrolled in our provincial cardiac arrest registry (Pavia CARe) from January 2015 to December 2017 were included and pre-hospital data were computed as well as survival to hospital discharge. RESULTS: Among 1401 resuscitation attempts, the LDB device was used in 235 (17%) patients. The LDB device was significantly more used for shockable cardiac arrest (42.6% vs 13.7%, p < 0.001). The rate of ROSC and of survival to hospital discharge in the LDB group compared to the manual group was 40% vs 17% (p < 0.001) and 10% vs 7% (p = 0.2), respectively. However, after correction for independent predictors of LDB use, LDB device was a strong independent predictor of survival to hospital discharge only for non-shockable witnessed OHCA [n = 624/1401, OR 11.9 (95% CI 1.5-95.2), p = 0.02]. In this categories of patients LDB group showed longer resuscitation time [49.3 min (IQR 37-71) vs 23.6 (IQR 15-35), p < 0.001] and a higher rate of conversion to a shockable rhythm (33/83 = 40% vs 29/541 = 5%, p < 0.001). CONCLUSION: Utstein categories-based analysis showed that the LDB device positively affect survival to hospital discharge for non-shockable witnessed cardiac arrests with a neutral effect for shockable rhythms.

[Bleeding risk in patients with acute coronary syndromes treated with antiplatelet agents: incidence, prognosis and clinical evaluation. From research to clinical practice]. / Il rischio di sanguinamento nei pazienti con sindrome coronarica acuta trattati con farmaci antiaggreganti: incidenza, impatto prognostico e metodi di valutazione, dagli studi alla pratica clinica.

Dual antiplatelet therapy (DAPT) including aspirin and a P2Y12 inhibitor is the cornerstone for the treatment of patients with acute coronary syndrome (ACS). The introduction of more potent drugs significantly reduced ischemic events, but with an associated increased risk of bleeding. Although appropriate estimation of bleeding risk by comparing the single drugs is challenging, mainly because of differences in definitions, it has been consistently shown that bleeding events are associated with an adverse outcome, both at short and long-term follow-up.Current guidelines recommend a short DAPT in patients at high bleeding risk, making appropriate risk estimation of crucial importance. Several numerical scores have been proposed for use in daily clinical practice. Although an objective risk assessment provides superior risk discrimination compared to physician's estimation, none of these scores appear free from limitations, nor have been obtained from cohorts of patients on short-tern treatment with prasugrel or ticagrelor. In the present review, we report the rates of major bleeding observed in the main randomized clinical trials and registries, their association with mortality, differences in definitions when used as safety endpoint, and finally the scores currently used for evaluation in daily clinical practice.

Correction: Persistent abnormalities in pulmonary arterial compliance after heart transplantation in patients with combined post-capillary and pre-capillary pulmonary hypertension.

[This corrects the article DOI: 10.1371/journal.pone.0188383.].

Different forms of pulmonary hypertension in a family with clinical and genetic evidence for hereditary hemorrhagic teleangectasia type 2.

Hereditary hemorrhagic telangiectasia (HTT) is an autosomal dominant disease, most frequently caused by a mutation in either ENG or ACVRL1, which can be associated with pulmonary arterial hypertension (PAH). In this report, we describe a new unpublished ACVRL1 mutation segregating in three members of the same family, showing three different types of pulmonary hypertension (PH) in the absence of BMPR2 mutations. The first patient has a form of heritable PAH (HPAH) in the absence of hepatic arteriovenous malformations (AVMs); the second one has a severe form of portopulmonary hypertension (PoPAH) associated with multiple hepatic AVMs; the third one has hepatopulmonary syndrome (HPS) with numerous hepatic arteriovenous fistulas and a form of post-capillary PH due to high cardiac output. In summary, a single mutation in the ACVRL1 gene can be associated, in the same family, with an extreme phenotypic variability regarding not only the clinical presentation of HHT but also the type of PH in the absence of BMPR2 mutations. More studies are needed to evaluate if this variability can be explained by the presence of additional variants in other genes relevant for the pathogenesis of HHT.