Publications by authors named "Dimitrios Alexopoulos"

329 Publications

Evaluation of optimal medical therapy in acute myocardial infarction patients with prior stroke.

Ther Adv Chronic Dis 2021 29;12:20406223211046999. Epub 2021 Sep 29.

Interventional Cardiology, University Clinic of Cardiology, Skopje, Former Yugoslav Republic of Macedonia (FYROM).

Background: Treatment of acute myocardial infarction (AMI) patients with prior stroke is a common clinical dilemma. Currently, the application of optimal medical therapy (OMT) and its impact on clinical outcomes are not clear in this patient population.

Methods: We retrieved 765 AMI patients with prior stroke who underwent percutaneous coronary intervention (PCI) during the index hospitalization from the international multicenter BleeMACS registry. All of the subjects were divided into two groups based on the prescription they were given prior to discharge. Baseline characteristics and procedural variables were compared between the OMT and non-OMT groups. Mortality, re-AMI, major adverse cardiovascular events (MACE), and bleeding were followed-up for 1 year.

Results: Approximately 5% of all patients presenting with AMI were admitted to the hospital for ischemic stroke. Although the prescription rate of each OMT medication was reasonably high (73.3%-97.3%), 47.7% lacked at least one OMT medication. Patients receiving OMT showed a significantly decreased occurrence of mortality (4.5% vs 15.1%,  < 0.001), re-AMI (4.2% vs 9.3%,  = 0.004), and the composite endpoint of death/re-AMI (8.6% vs 20.5%,  < 0.001) compared to those without OMT. No significant difference was observed between the groups regarding bleeding. After adjusting for confounding factors, OMT was the independent protective factor of 1-year mortality, while age was the independent risk factors.

Conclusions: OMT at discharge was associated with a significantly lower 1-year mortality of patients with AMI and prior stroke in clinical practice. However, OMT was provided to just half of the eligible patients, leaving room for substantial improvement.

Clinical Trial Registration: NCT02466854.
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http://dx.doi.org/10.1177/20406223211046999DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8485283PMC
September 2021

COVID-19 pandemic, mechanical reperfusion and 30-day mortality in ST elevation myocardial infarction.

Heart 2021 Oct 28. Epub 2021 Oct 28.

Department of Cardiology, University of Patras, Patras, Greece.

Objective: The initial data of the International Study on Acute Coronary Syndromes - ST Elevation Myocardial Infarction COVID-19 showed in Europe a remarkable reduction in primary percutaneous coronary intervention procedures and higher in-hospital mortality during the initial phase of the pandemic as compared with the prepandemic period. The aim of the current study was to provide the final results of the registry, subsequently extended outside Europe with a larger inclusion period (up to June 2020) and longer follow-up (up to 30 days).

Methods: This is a retrospective multicentre registry in 109 high-volume primary percutaneous coronary intervention (PPCI) centres from Europe, Latin America, South-East Asia and North Africa, enrolling 16 674 patients with ST segment elevation myocardial infarction (STEMI) undergoing PPPCI in March/June 2019 and 2020. The main study outcomes were the incidence of PPCI, delayed treatment (ischaemia time >12 hours and door-to-balloon >30 min), in-hospital and 30-day mortality.

Results: In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio 0.843, 95% CI 0.825 to 0.861, p<0.0001). This reduction was significantly associated with age, being higher in older adults (>75 years) (p=0.015), and was not related to the peak of cases or deaths due to COVID-19. The heterogeneity among centres was high (p<0.001). Furthermore, the pandemic was associated with a significant increase in door-to-balloon time (40 (25-70) min vs 40 (25-64) min, p=0.01) and total ischaemia time (225 (135-410) min vs 196 (120-355) min, p<0.001), which may have contributed to the higher in-hospital (6.5% vs 5.3%, p<0.001) and 30-day (8% vs 6.5%, p=0.001) mortality observed during the pandemic.

Conclusion: Percutaneous revascularisation for STEMI was significantly affected by the COVID-19 pandemic, with a 16% reduction in PPCI procedures, especially among older patients (about 20%), and longer delays to treatment, which may have contributed to the increased in-hospital and 30-day mortality during the pandemic.

Trial Registration Number: NCT04412655.
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http://dx.doi.org/10.1136/heartjnl-2021-319750DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8561823PMC
October 2021

Does ventricle size contribute to cognitive outcomes in posthemorrhagic hydrocephalus? Role of early definitive intervention.

J Neurosurg Pediatr 2021 Oct 15:1-11. Epub 2021 Oct 15.

1Departments of Neurological Surgery.

Objective: Posthemorrhagic hydrocephalus (PHH) is associated with significant morbidity, smaller hippocampal volumes, and impaired neurodevelopment in preterm infants. The timing of temporary CSF (tCSF) diversion has been studied; however, the optimal time for permanent CSF (pCSF) diversion is unknown. The objective of this study was to determine whether cumulative ventricle size or timing of pCSF diversion is associated with neurodevelopmental outcome and hippocampal size in preterm infants with PHH.

Methods: Twenty-five very preterm neonates (born at ≤ 32 weeks' gestational age) with high-grade intraventricular hemorrhage (IVH), subsequent PHH, and pCSF diversion with a ventriculoperitoneal shunt (n = 20) or endoscopic third ventriculostomy (n = 5) were followed until 2 years of age. Infants underwent serial cranial ultrasounds from birth until 1 year after pCSF diversion, brain MRI at term-equivalent age, and assessment based on the Bayley Scales of Infant and Toddler Development, Third Edition, at 2 years of age. Frontooccipital horn ratio (FOHR) measurements were derived from cranial ultrasounds and term-equivalent brain MRI. Hippocampal volumes were segmented and calculated from term-equivalent brain MRI. Cumulative ventricle size until the time of pCSF diversion was estimated using FOHR measurements from each cranial ultrasound performed prior to permanent intervention.

Results: The average gestational ages at tCSF and pCSF diversion were 28.9 and 39.0 weeks, respectively. An earlier chronological age at the time of pCSF diversion was associated with larger right hippocampal volumes on term-equivalent MRI (Pearson's r = -0.403, p = 0.046) and improved cognitive (r = -0.554, p = 0.047), motor (r = -0.487, p = 0.048), and language (r = -0.414, p = 0.021) outcomes at 2 years of age. Additionally, a smaller cumulative ventricle size from birth to pCSF diversion was associated with larger right hippocampal volumes (r = -0.483, p = 0.014) and improved cognitive (r = -0.711, p = 0.001), motor (r = -0.675, p = 0.003), and language (r = -0.618, p = 0.011) outcomes. There was no relationship between time to tCSF diversion or cumulative ventricle size prior to tCSF diversion and neurodevelopmental outcome or hippocampal size. Finally, a smaller cumulative ventricular size prior to either tCSF diversion or pCSF diversion was associated with a smaller ventricular size 1 year after pCSF diversion (r = 0.422, p = 0.040, R2 = 0.178 and r = 0.519, p = 0.009, R2 = 0.269, respectively).

Conclusions: In infants with PHH, a smaller cumulative ventricular size and shorter time to pCSF diversion were associated with larger right hippocampal volumes, improved neurocognitive outcomes, and reduced long-term ventriculomegaly. Future prospective randomized studies are needed to confirm these findings.
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http://dx.doi.org/10.3171/2021.4.PEDS212DOI Listing
October 2021

Saphenous Vein Graft Failure: From Pathophysiology to Prevention and Treatment Strategies.

Circulation 2021 Aug 30;144(9):728-745. Epub 2021 Aug 30.

Center for Coronary Artery Disease, Minneapolis Heart Institute and Minneapolis Heart Institute Foundation, Abbott Northwestern, MN (I.X., I.N., E.V., J.K., M.N.B., V.N.B., E.S.B.).

Saphenous vein grafts (SVGs) remain the most frequently used conduits in coronary artery bypass graft surgery (CABG). Despite advances in surgical techniques and pharmacotherapy, SVG failure rates remain high, often leading to repeat coronary revascularization. The no-touch SVG harvesting technique (minimal graft manipulation with preservation of vasa vasorum and nerves) reduces the risk of SVG failure, whereas the effect of the off-pump technique on SVG patency remains unclear. Use of buffered storage solutions, intraoperative graft flow measurement, careful selection of the target vessels, and physiological assessment of the native coronary circulation before CABG may also reduce the incidence of SVG failure. Perioperative aspirin and high-intensity statin administration are the cornerstones of secondary prevention after CABG. Dual antiplatelet therapy is recommended for off-pump CABG and in patients with a recent acute coronary syndrome. Intermediate (30%-60%) SVG stenoses often progress rapidly. Stenting of intermediate SVG stenoses failed to improve outcomes; hence, treatment focuses on strict control of coronary artery disease risk factors. Redo CABG is associated with higher perioperative mortality compared with percutaneous coronary intervention (PCI); hence, the latter is preferred for most patients requiring repeat revascularization after CABG. SVG PCI is limited by high rates of no-reflow and a high incidence of restenosis during follow-up. Drug-eluting and bare metal stents provide similar long-term outcomes in SVG PCI. Embolic protection devices reduce no-reflow and should be used when feasible. PCI of the corresponding native coronary artery is associated with better short- and long-term outcomes and is preferred over SVG PCI, if technically feasible.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052163DOI Listing
August 2021

Parallel hippocampal-parietal circuits for self- and goal-oriented processing.

Proc Natl Acad Sci U S A 2021 08;118(34)

Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110;

The hippocampus is critically important for a diverse range of cognitive processes, such as episodic memory, prospective memory, affective processing, and spatial navigation. Using individual-specific precision functional mapping of resting-state functional MRI data, we found the anterior hippocampus (head and body) to be preferentially functionally connected to the default mode network (DMN), as expected. The hippocampal tail, however, was strongly preferentially functionally connected to the parietal memory network (PMN), which supports goal-oriented cognition and stimulus recognition. This anterior-posterior dichotomy of resting-state functional connectivity was well-matched by differences in task deactivations and anatomical segmentations of the hippocampus. Task deactivations were localized to the hippocampal head and body (DMN), relatively sparing the tail (PMN). The functional dichotomization of the hippocampus into anterior DMN-connected and posterior PMN-connected parcels suggests parallel but distinct circuits between the hippocampus and medial parietal cortex for self- versus goal-oriented processing.
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http://dx.doi.org/10.1073/pnas.2101743118DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8403906PMC
August 2021

Reperfusion therapies and in-hospital outcomes for ST-elevation myocardial infarction in Europe: the ACVC-EAPCI EORP STEMI Registry of the European Society of Cardiology.

Eur Heart J 2021 11;42(44):4536-4549

Spitalul Clinic de Urgenta "Floreasca", Calea Floreasca 8, București 014461, Romania.

Aims: The aim of this study was to determine the contemporary use of reperfusion therapy in the European Society of Cardiology (ESC) member and affiliated countries and adherence to ESC clinical practice guidelines in patients with ST-elevation myocardial infarction (STEMI).

Methods And Results: Prospective cohort (EURObservational Research Programme STEMI Registry) of hospitalized STEMI patients with symptom onset <24 h in 196 centres across 29 countries. A total of 11 462 patients were enrolled, for whom primary percutaneous coronary intervention (PCI) (total cohort frequency: 72.2%, country frequency range 0-100%), fibrinolysis (18.8%; 0-100%), and no reperfusion therapy (9.0%; 0-75%) were performed. Corresponding in-hospital mortality rates from any cause were 3.1%, 4.4%, and 14.1% and overall mortality was 4.4% (country range 2.5-5.9%). Achievement of quality indicators for reperfusion was reported for 92.7% (region range 84.8-97.5%) for the performance of reperfusion therapy of all patients with STEMI <12 h and 54.4% (region range 37.1-70.1%) for timely reperfusion.

Conclusions: The use of reperfusion therapy for STEMI in the ESC member and affiliated countries was high. Primary PCI was the most frequently used treatment and associated total in-hospital mortality was below 5%. However, there was geographic variation in the use of primary PCI, which was associated with differences in in-hospital mortality.
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http://dx.doi.org/10.1093/eurheartj/ehab342DOI Listing
November 2021

Optical Coherence Tomography for ST-Segment Elevation Myocardial Infarction: When the Occluded Vessel is not the Culprit.

Hellenic J Cardiol 2021 Jul 26. Epub 2021 Jul 26.

Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.

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http://dx.doi.org/10.1016/j.hjc.2021.07.004DOI Listing
July 2021

Persistent decline of hospitalizations for acute stroke and acute coronary syndrome during the second wave of the COVID-19 pandemic in Greece: collateral damage unaffected.

Ther Adv Neurol Disord 2021 7;14:17562864211029540. Epub 2021 Jul 7.

Second Department of Neurology, ATTIKON University Hospital, National and Kapodistrian University of Athens, Athens, Greece.

Background: An alarming cerebro/cardiovascular collateral damage, reflected by a decline in admissions for acute stroke (AS) and acute coronary syndrome (ACS), was observed during the initial phase of the COVID-19 pandemic, thereby leading to a re-design of public campaigns. However, there are limited data regarding the AS and ACS hospitalization rates during the second wave of the pandemic, which was followed by re-imposition of lockdowns.

Methods: We calculated the rate of AS and ACS hospitalizations from three representative tertiary care hospitals in Greece during a 2-month period (November-December 2020) of the second wave of the COVID-19 pandemic compared with the corresponding control period in 2019 from three representative tertiary care hospitals in Greece. This was a follow-up study with identical design to our previous report evaluating AS and ACS hospitalizations during the first wave of the pandemic (March-April 2020).

Results: Compared with 2019, there was a 34% relative reduction of AS hospitalizations [incidence rate ratio (IRR): 0.66, 95% confidence interval (CI): 0.48-0.92,  = 0.013] and 33% relative reduction of ACS hospitalizations (IRR: 0.67, 95% CI: 0.54-0.83,  < 0.001) during the second wave of the COVID-19 pandemic. The relative reduction was smaller and did not reach the level of statistical significance for the respective syndromes (haemorrhagic stroke: IRR 0.87, 95% CI: 0.41-1.82,  = 0.71; ST-elevation myocardial infarction: IRR 0.81, 95% CI: 0.57-1.14,  = 0.22).

Conclusion: AS and ACS hospitalizations were persistently reduced during the second wave of the COVID-19 pandemic compared with 2019 in Greece. This decline was similar to the observations during the first wave despite the large differences in the epidemiological COVID-19 burden. Lockdowns, a common characteristic in both waves, appear to have a detrimental indirect impact on cerebro/cardiovascular diseases in the general population.
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http://dx.doi.org/10.1177/17562864211029540DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8267023PMC
July 2021

Alterations in resting-state functional connectivity in pediatric patients with tuberous sclerosis complex.

Epilepsia Open 2021 Sep 3;6(3):579-587. Epub 2021 Aug 3.

Department of Neurology, Washington University, St. Louis, MO, USA.

Objective: To investigate resting-state functional connectivity (FC) in pediatric patients with tuberous sclerosis complex and intractable epilepsy requiring surgery.

Methods: Resting-state functional MRI was utilized to investigate functional connectivity in 13 pediatric patients with tuberous sclerosis complex (TSC) and intractable epilepsy requiring surgery.

Results: The majority of patients demonstrated a resting-state network architecture similar to those reported in healthy individuals. However, preoperative differences were evident between patients with high versus low tuber burden, as well as those with good versus poor neurodevelopmental outcomes, most notably in the cingulo-opercular and visual resting-state networks. One patient with high tuber burden and poor preoperative development and seizure control had nearly normal development and seizure resolution after surgery. This was accompanied by significant improvement in resting-state network architecture just one day postoperatively.

Significance: Although many patients with tuberous sclerosis complex and medically refractory epilepsy demonstrate functional connectivity patterns similar to healthy children, relationships within and between RSNs demonstrate clear differences in patients with higher tuber burden and worse outcomes. Improvements in resting-state network organization postoperatively may be related to epilepsy surgery outcomes, providing candidate biomarkers for clinical management in this high-risk population.
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http://dx.doi.org/10.1002/epi4.12523DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8408601PMC
September 2021

Shockwave coronary intravascular lithotripsy system for heavily calcified de novo lesions and the need for a cost-effectiveness analysis.

Cardiovasc Revasc Med 2021 Jul 5. Epub 2021 Jul 5.

1st Cardiology Department, AHEPA General Hospital, Aristotle University of Thessaloniki, Greece.

The optimal management for severely calcified coronary artery disease is multi-adjunctive. Different strategies with dedicated devices should be available in the cardiac catheterization laboratory with their selection depending on the nature of the calcific disease and its anatomical distribution. Shockwave Intravascular Lithotripsy (S-IVL) system offers a novel option for lesion preparation of heavily calcified plaques in coronary and peripheral vessels. S-IVL is based on the fundamental principles of lithotripsy, a technology that has been used to modify renal stones for over 30 years. Pulsatile mechanical energy is used to fragment selectively amorphous calcium, sparing soft tissue. S-IVL has the potential of more widespread adoption because of its proven safety, efficacy and operational simplicity, but cost-effectiveness of such advanced technology will need to be analyzed.
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http://dx.doi.org/10.1016/j.carrev.2021.06.125DOI Listing
July 2021

Ticagrelor or Clopidogrel After an Acute Coronary Syndrome in the Elderly: A Propensity Score Matching Analysis from 16,653 Patients Treated with PCI Included in Two Large Multinational Registries.

Cardiovasc Drugs Ther 2021 12 5;35(6):1171-1182. Epub 2021 Jul 5.

Department of Cardiovascular Medicine, Kanazawa University Graduate School of Medical Sciences, Kanazawa, Japan.

Purpose: Higher risk of bleeding with ticagrelor over clopidogrel in elderly patients with acute coronary syndrome (ACS) who underwent percutaneous coronary intervention (PCI) has been suggested. We assessed the incidence of major bleedings (MB), reinfarction (re-MI), and all-cause death to evaluate safety and efficacy of ticagrelor versus clopidogrel in such population.

Methods: Real-world registries RENAMI and BleeMACS were merged. The pooled cohort was divided into two groups, clopidogrel versus ticagrelor. Statistical analysis considered patients <75 versus ≥75 years old. Endpoints were BARC 3-5 MB, re-MI, and all-cause death at 1-year follow-up. The study included 16,653 patients (13,153 < 75 and 3500 ≥ 75 years). Ticagrelor was underused in elderly patients (16.3% versus 20.8%, P < 0.001). Using propensity score matching (PSM), two treatment groups of 1566 patients were included in the final analysis.

Results: Ticagrelor was able to prevent re-MI (hazard ratio [HR], 0.31; 95% confidence interval [CI], 0.2-0.6; P < 0.001) and all-cause death (HR, 0.60; 95% CI, 0.4-0.9; P = 0.026) irrespective of age. In patients ≥75 years, ticagrelor reduced all-cause death (HR, 0.32; 95% CI, 0.1-0.8; P = 0.012) and re-MI (HR, 0.25; 95% CI, 0.1-1.1, P = 0.072). Moreover, even with the limit of the low number of events, ticagrelor did not significantly increase the incidence of MB (HR, 1.49; 95% CI, 0.70-3.0; P = 0.257). At multiple Cox regression, age (HR, 1.03; 95% CI, 1.02-1.05; P < 0.001) resulted an independent risk factor for bleeding.

Conclusion: In our study, reflecting the results from two large retrospective, real-world registries, Ticagrelor did not significantly increase MB compared with clopidogrel in elderly patients with ACS treated with PCI, while significantly improving 1-year survival. Further studies on elderly patients are suggested.
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http://dx.doi.org/10.1007/s10557-021-07213-yDOI Listing
December 2021

Pharmacodynamic Effects of Pre-Hospital Administered Crushed Prasugrel in Patients With ST-Segment Elevation Myocardial Infarction.

JACC Cardiovasc Interv 2021 06;14(12):1323-1333

Department of Cardiology, University Medical Center Utrecht, Utrecht, the Netherlands; Department of Cardiology, Maasstad Hospital, Rotterdam, the Netherlands. Electronic address:

Objectives: This study sought to compare the pharmacodynamic effects of pre-hospitally administered P2Y inhibitor prasugrel in crushed versus integral tablet formulation in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (pPCI).

Background: Early dual antiplatelet therapy is recommended in STEMI patients. Yet, onset of oral P2Y inhibitor effect is delayed and varies according to formulation administered.

Methods: The COMPARE CRUSH (Comparison of Pre-hospital Crushed Versus Uncrushed Prasugrel Tablets in Patients With STEMI Undergoing Primary Percutaneous Coronary Interventions) trial randomized patients with suspected STEMI to crushed or integral prasugrel 60-mg loading dose in the ambulance. Pharmacodynamic measurements were performed at 4 time points: before antiplatelet treatment, at the beginning and end of pPCI, and 4 h after study treatment onset. The primary endpoint was high platelet reactivity at the end of pPCI. The secondary endpoint was impact of platelet reactivity status on markers of coronary reperfusion.

Results: A total of 441 patients were included. In patients with crushed prasugrel, the occurrence of high platelet reactivity at the end of pPCI was reduced by almost one-half (crushed 34.7% vs. uncrushed 61.6%; odds ratio [OR] = 0.33; 95% confidence interval [CI] = 0.22 to 0.50; p < 0.01). Platelet reactivity <150 P2Y reactivity units at the beginning of coronary angiography correlated with improved Thrombolysis In Myocardial Infarction flow grade 3 in the infarct artery pre-pPCI (OR: 1.78; 95% CI: 1.08 to 2.94; p = 0.02) but not ST-segment resolution (OR: 0.80; 95% CI: 0.48 to 1.34; p = 0.40).

Conclusions: Oral administration of crushed compared with integral prasugrel significantly improves platelet inhibition during the acute phase in STEMI patients undergoing pPCI. However, a considerable number of patients still exhibit inadequate platelet inhibition at the end of pPCI, suggesting the need for alternative agents to bridge the gap in platelet inhibition.
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http://dx.doi.org/10.1016/j.jcin.2021.04.022DOI Listing
June 2021

Ticagrelor versus prasugrel in acute coronary syndrome: sex-specific analysis from the RENAMI Registry.

Minerva Cardiol Angiol 2021 Aug 17;69(4):408-416. Epub 2021 Jun 17.

General University Hospital of Patras, Rion, Patras, Greece.

Background: The use of potent P2Y12 inhibitors (ticagrelor & prasugrel) in acute coronary syndrome (ACS) patients undergoing percutaneous coronary interventions (PCI) is a class I recommendation. We performed a sex-specific analysis comparing the difference in efficacy and safety outcomes between ticagrelor and prasugrel in a real-world ACS population.

Methods: Data from the multicenter REgistry of New Antiplatelets in patients with Myocardial Infarction (RENAMI) for 4424 ACS patients who underwent PCI and were treated with ticagrelor or prasugrel between 2012 to 2016 were analyzed. Mean follow-up was 17±9 months.

Results: After propensity score matching, there was no significant difference in the occurrence of primary endpoint of net adverse cardiac events between ticagrelor and prasugrel in men (HR: 0.94; 95% CI: 0.69-1.29; P=0.71), or women (HR: 1.17; 95% CI: 0.63-2.20; P=0.62; P interaction [sex] = 0.40). Similarly, no differences were found in the occurrence of any of the secondary endpoints (MACE, all cause death, re-infarction, stent thrombosis, BARC major bleeding and BARC any bleeding) between the two P2Y12 groups between men and women.

Conclusions: In this real-world ACS population, no relative difference in efficacy or safety outcomes were found between ticagrelor and prasugrel between sexes.
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http://dx.doi.org/10.23736/S2724-5683.21.05591-5DOI Listing
August 2021

Differential effects of heat-not-burn and conventional cigarettes on coronary flow, myocardial and vascular function.

Sci Rep 2021 06 3;11(1):11808. Epub 2021 Jun 3.

2nd Cardiology Department, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

We compared the effects of Heat-not-Burn cigarette (HNBC) to those of tobacco cigarette (Tcig), on myocardial, coronary and arterial function as well as on oxidative stress and platelet activation in 75 smokers. In the acute study, 50 smokers were randomised into smoking a single Tcig or a HNBC and after 60 min were crossed-over to the alternate smoking. For chronic phase, 50 smokers were switched to HNBC and were compared with an external group of 25 Tcig smokers before and after 1 month. Exhaled carbon monoxide (CO), pulse wave velocity (PWV), malondialdehyde (MDA) and thromboxane B2 (TxB2) were assessed in the acute and chronic study. Global longitudinal strain (GLS), myocardial work index (GWI), wasted myocardial work (GWW), coronary flow reserve (CFR), total arterial compliance (TAC) and flow-mediated dilation (FMD) were assessed in the chronic study. Acute HNBC smoking caused a smaller increase of PWV than Tcig (change 1.1 vs 0.54 m/s, p < 0.05) without change in CO and biomarkers in contrast to Tcig. Compared to Tcig, switching to HNBC for 1-month improved CO, FMD, CFR, TAC, GLS, GWW, MDA, TxB2 (differences 10.42 ppm, 4.3%, 0.98, 1.8 mL/mmHg, 2.35%, 19.72 mmHg%, 0.38 nmol/L and 45 pg/mL respectively, p < 0.05). HNBCs exert a less detrimental effect on vascular and cardiac function than tobacco cigarettes.Trial registration Registered on https://clinicaltrials.gov/ (NCT03452124, 02/03/2018).
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http://dx.doi.org/10.1038/s41598-021-91245-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8175445PMC
June 2021

Massive thrombus migration: thrombectomy to rescue.

Coron Artery Dis 2022 Jan;31(1):e21-e22

Second Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.

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http://dx.doi.org/10.1097/MCA.0000000000001057DOI Listing
January 2022

Seizure burden in preterm infants and smaller brain volume at term-equivalent age.

Pediatr Res 2021 Apr 26. Epub 2021 Apr 26.

Division of Newborn Medicine, Department of Pediatrics, Washington University, St. Louis, MO, USA.

Background: Seizures are underrecognized in preterm infants, and little is known about their impact on brain growth. We aimed to define the association between early seizures and subsequent brain growth.

Methods: Infants <30 weeks gestation underwent 72 h of prospective amplitude-integrated electroencephalography (aEEG) monitoring, term-equivalent age (TEA) magnetic resonance imaging (MRI), and 2-year neurodevelopmental testing. Seizures were defined as trains of sharp waves >10 s, evolving in frequency/amplitude/morphology, and identified using automated algorithms with manual review. Using T2-weighted images, cortical surface area (CSA) and gyrification index (GI) were calculated and volumes were segmented into five tissue classes: cerebrospinal fluid, gray matter, white matter (WM), deep nuclear gray matter, and cerebellum. Correlations between total seizure burden and tissue-specific volumes were evaluated, controlling for clinical variables of interest.

Results: Ninety-nine infants underwent aEEG/MRI assessments (mean GA = 26.3 weeks, birthweight = 899 g). Seizure incidence was 55% with a median of two events; median length = 66 s and mean burden = 285 s. Greater seizure burden was associated with smaller CSA and volumes across all tissue types, most prominently in WM (R = -0.603, p < 0.01), even after controlling for confounders. There was no association with GI.

Conclusions: Seizures in preterm infants are common and associated with smaller TEA brain volumes. This relationship was strongest for WM and independent of clinical factors.

Impact: Seizures in preterm infants are common. Little is known about the association between early seizures and later brain growth. Greater seizure burden is linked with smaller volumes of all brain tissue types, most prominently the WM. This relationship is true even controlling for other factors. Additional study is needed to identify the optimal EEG monitoring and seizure treatment strategy for improved brain growth and neurodevelopmental outcomes.
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http://dx.doi.org/10.1038/s41390-021-01542-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8546006PMC
April 2021

Not-high before-treatment platelet reactivity in patients with STEMI: prevalence, clinical characteristics, response to therapy and outcomes.

Platelets 2021 Apr 15:1-8. Epub 2021 Apr 15.

Cardiology Clinic, Sassari University Hospital, Sassari, Italy.

Platelet reactivity (PR) has been indicated as a pathophysiological key element for ST-Elevation Myocardial Infarction (STEMI) development. Patients with not-high before-treatment platelet reactivity (NHPR) have been poorly studied so far. The aim of this study is to investigate the prevalence, clinical characteristics, response to therapy and outcomes of baseline prior to treatment NHPR among patients with STEMI undergoing primary PCI.We analyzed the data from 358 STEMI patients with assessment of PR by VerifyNow before P2Y inhibitor loading dose (LD). Blood samples were obtained at baseline, and after 1 hour, 2 hours, 4-6 hours and 8-12 hours after LD. High platelet reactivity (HPR) was defined as Platelet Reactivity Unit values ≥208, while patients with values <208 at baseline were defined as having NHPR.Overall, 20% patients had NHPR. Age and male gender both resulted independent predictors of NHPR, even after propensity score adjustment. The percentage of inhibition of PR after ticagrelor or prasugrel LD was similar between HPR and NHPR patients at each time point. However, patients with HPR showed worse in-hospital clinical outcomes, and the composite adverse outcome endpoint of death, reinfarction, stroke, acute kidney injury or heart failure was significantly higher (10.0% vs 1.4%; = .017) as compared with the NHPR group.In conclusion, a significant proportion of patients presenting with STEMI has a baseline NHPR that is associated with better in-hospital outcomes as compared with patients with HPR. Further studies are needed to better elucidate the potential therapeutic implications of NHPR in terms of secondary prevention.
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http://dx.doi.org/10.1080/09537104.2021.1915973DOI Listing
April 2021

Vascular conditioning prevents adverse left ventricular remodelling after acute myocardial infarction: a randomised remote conditioning study.

Basic Res Cardiol 2021 02 6;116(1). Epub 2021 Feb 6.

2nd Department of Cardiology, Medical School, Attikon Hospital, National and Kapodistrian University of Athens, Rimini 1, Haidari, 12462, Athens, Greece.

Aims: Remote ischemic conditioning (RIC) alleviates ischemia-reperfusion injury via several pathways, including micro-RNAs (miRs) expression and oxidative stress modulation. We investigated the effects of RIC on endothelial glycocalyx, arterial stiffness, LV remodelling, and the underlying mediators within the vasculature as a target for protection.

Methods And Results: We block-randomised 270 patients within 48 h of STEMI post-PCI to either one or two cycles of bilateral brachial cuff inflation, and a control group without RIC. We measured: (a) the perfusion boundary region (PBR) of the sublingual arterial microvessels to assess glycocalyx integrity; (b) the carotid-femoral pulse wave velocity (PWV); (c) miR-144,-150,-21,-208, nitrate-nitrite (NOx) and malondialdehyde (MDA) plasma levels at baseline (T0) and 40 min after RIC onset (T3); and (d) LV volumes at baseline and after one year. Compared to baseline, there was a greater PBR and PWV decrease, miR-144 and NOx levels increase (p < 0.05) at T3 following single- than double-cycle inflation (PBR:ΔT0-T3 = 0.249 ± 0.033 vs 0.126 ± 0.034 μm, p = 0.03 and PWV:0.4 ± 0.21 vs -1.02 ± 0.24 m/s, p = 0.03). Increased miR-150,-21,-208 (p < 0.05) and reduced MDA was observed after both protocols. Increased miR-144 was related to PWV reduction (r = 0.763, p < 0.001) after the first-cycle inflation in both protocols. After one year, single-cycle RIC was associated with LV end-systolic volume reduction (LVESV) > 15% (odds-ratio of 3.75, p = 0.029). MiR-144 and PWV changes post-RIC were interrelated and associated with LVESV reduction at follow-up (r = 0.40 and 0.37, p < 0.05), in the single-cycle RIC.

Conclusion: RIC evokes "vascular conditioning" likely by upregulation of cardio-protective microRNAs, NOx production, and oxidative stress reduction, facilitating reverse LV remodelling.

Clinical Trial Registration: http://www.clinicaltrials.gov . Unique identifier: NCT03984123.
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http://dx.doi.org/10.1007/s00395-021-00851-1DOI Listing
February 2021

Dual Antithrombotic Therapy in Atrial Fibrillation Patients undergoing Percutaneous Coronary Angioplasty: The Impact of Bleeding Risk Score on Outcome.

Thromb Haemost 2021 06 30;121(6):845-847. Epub 2020 Dec 30.

2nd Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece.

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http://dx.doi.org/10.1055/s-0040-1721777DOI Listing
June 2021

Impact of COVID-19 pandemic and diabetes on mechanical reperfusion in patients with STEMI: insights from the ISACS STEMI COVID 19 Registry.

Cardiovasc Diabetol 2020 12 18;19(1):215. Epub 2020 Dec 18.

Central Hospital of Medical University of Lodz, Łódź, Poland.

Background: It has been suggested the COVID pandemic may have indirectly affected the treatment and outcome of STEMI patients, by avoidance or significant delays in contacting the emergency system. No data have been reported on the impact of diabetes on treatment and outcome of STEMI patients, that was therefore the aim of the current subanalysis conducted in patients included in the International Study on Acute Coronary Syndromes-ST Elevation Myocardial Infarction (ISACS-STEMI) COVID-19.

Methods: The ISACS-STEMI COVID-19 is a retrospective registry performed in European centers with an annual volume of > 120 primary percutaneous coronary intervention (PCI) and assessed STEMI patients, treated with primary PCI during the same periods of the years 2019 versus 2020 (March and April). Main outcomes are the incidences of primary PCI, delayed treatment, and in-hospital mortality.

Results: A total of 6609 patients underwent primary PCI in 77 centers, located in 18 countries. Diabetes was observed in a total of 1356 patients (20.5%), with similar proportion between 2019 and 2020. During the pandemic, there was a significant reduction in primary PCI as compared to 2019, similar in both patients with (Incidence rate ratio (IRR) 0.79 (95% CI: 0.73-0.85, p < 0.0001) and without diabetes (IRR 0.81 (95% CI: 0.78-0.85, p < 0.0001) (p int = 0.40). We observed a significant heterogeneity among centers in the population with and without diabetes (p < 0.001, respectively). The heterogeneity among centers was not related to the incidence of death due to COVID-19 in both groups of patients. Interaction was observed for Hypertension (p = 0.024) only in absence of diabetes. Furthermore, the pandemic was independently associated with a significant increase in door-to-balloon and total ischemia times only among patients without diabetes, which may have contributed to the higher mortality, during the pandemic, observed in this group of patients.

Conclusions: The COVID-19 pandemic had a significant impact on the treatment of patients with STEMI, with a similar reduction in primary PCI procedures in both patients with and without diabetes. Hypertension had a significant impact on PCI reduction only among patients without diabetes. We observed a significant increase in ischemia time and door-to-balloon time mainly in absence of diabetes, that contributed to explain the increased mortality observed in this group of patients during the pandemic.

Trial Registration Number: NCT04412655.
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http://dx.doi.org/10.1186/s12933-020-01196-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7747477PMC
December 2020

Effect of Prehospital Crushed Prasugrel Tablets in Patients With ST-Segment-Elevation Myocardial Infarction Planned for Primary Percutaneous Coronary Intervention: The Randomized COMPARE CRUSH Trial.

Circulation 2020 12 14;142(24):2316-2328. Epub 2020 Oct 14.

Maasstad Hospital, Rotterdam, The Netherlands (G.J.V., V.P., P.C.S.).

Background: Early treatment with a potent oral platelet P2Y inhibitor is recommended in patients presenting with ST-segment-elevation myocardial infarction scheduled to undergo primary percutaneous coronary intervention (pPCI). The impact on coronary reperfusion of crushed P2Y inhibitor tablets, which lead to more prompt and potent platelet inhibition, is unknown.

Methods: We conducted a randomized controlled, multicenter trial in the Netherlands, enrolling patients with ST-segment-elevation myocardial infarction scheduled to undergo pPCI. Patients were randomly allocated to receive in the ambulance, before transfer, a 60-mg loading dose of prasugrel either as crushed or integral tablets. The independent primary end points were thrombolysis in myocardial infarction (TIMI) 3 flow in the infarct-related artery at initial coronary angiography, and complete (≥70%) ST-segment resolution 1 hour after pPCI. The safety end points were TIMI major and Bleeding Academic Research Consortium ≥3 bleedings. Secondary end points included platelet reactivity and ischemic outcomes.

Results: A total of 727 patients were assigned to either crushed or integral tablets of prasugrel loading dose. The median time from study treatment to wire-crossing during pPCI was 57 (47-70) minutes. The primary end point TIMI 3 flow in the infarct-related artery before pPCI occurred in 31.0% in the crushed group versus 32.7% in the integral group (odds ratio, 0.92 [95% CI, 0.65-1.30], =0.64). Complete ST-segment resolution 1 hour after pPCI was present in 59.9% in the crushed group versus 57.3% in the integral group (odds ratio, 1.11 [95% CI, 0.78-1.58], =0.55). Platelet reactivity at the beginning of pPCI, measured as P2Y reactivity unit, differed significantly between groups (crushed, 192 [132-245] versus integral, 227 [184-254], ≤0.01). TIMI major and Bleeding Academic Research Consortium ≥3 bleeding occurred in 0% in the crushed group versus 0.8% in the integral group, and in 0.3% in the crushed group versus 1.1% in the integral group, respectively. There were no differences observed between groups regarding ischemic events at 30 days.

Conclusions: Prehospital administration of crushed prasugrel tablets does not improve TIMI 3 flow in the infarct-related artery before pPCI or complete ST-segment resolution 1 h after pPCI in patients presenting with ST-segment-elevation myocardial infarction scheduled for pPCI. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03296540.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.051532DOI Listing
December 2020

Impact of COVID-19 Pandemic on Mechanical Reperfusion for Patients With STEMI.

J Am Coll Cardiol 2020 11;76(20):2321-2330

Division of Cardiology, Ospedale "Sant'Anna", Ferrara, Italy.

Background: The fear of contagion during the coronavirus disease-2019 (COVID-19) pandemic may have potentially refrained patients with ST-segment elevation myocardial infarction (STEMI) from accessing the emergency system, with subsequent impact on mortality.

Objectives: The ISACS-STEMI COVID-19 registry aims to estimate the true impact of the COVID-19 pandemic on the treatment and outcome of patients with STEMI treated by primary percutaneous coronary intervention (PPCI), with identification of "at-risk" patient cohorts for failure to present or delays to treatment.

Methods: This retrospective registry was performed in European high-volume PPCI centers and assessed patients with STEMI treated with PPPCI in March/April 2019 and 2020. Main outcomes are the incidences of PPCI, delayed treatment, and in-hospital mortality.

Results: A total of 6,609 patients underwent PPCI in 77 centers, located in 18 countries. In 2020, during the pandemic, there was a significant reduction in PPCI as compared with 2019 (incidence rate ratio: 0.811; 95% confidence interval: 0.78 to 0.84; p < 0.0001). The heterogeneity among centers was not related to the incidence of death due to COVID-19. A significant interaction was observed for patients with arterial hypertension, who were less frequently admitted in 2020 than in 2019. Furthermore, the pandemic was associated with a significant increase in door-to-balloon and total ischemia times, which may have contributed to the higher mortality during the pandemic.

Conclusions: The COVID-19 pandemic had significant impact on the treatment of patients with STEMI, with a 19% reduction in PPCI procedures, especially among patients suffering from hypertension, and a longer delay to treatment, which may have contributed to the increased mortality during the pandemic. (Primary Angioplasty for STEMI During COVID-19 Pandemic [ISACS-STEMI COVID-19] Registry; NCT04412655).
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http://dx.doi.org/10.1016/j.jacc.2020.09.546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7834750PMC
November 2020

Ticagrelor and omeprazole: A desirable combination in post MI patients?

Hellenic J Cardiol 2020 Sep - Oct;61(5):311-312. Epub 2020 Nov 9.

2nd Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Athens, Greece. Electronic address:

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http://dx.doi.org/10.1016/j.hjc.2020.10.002DOI Listing
May 2021

Prolonged antithrombotic therapy in patients after acute coronary syndrome: A critical appraisal of current European Society of Cardiology guidelines.

Cardiol J 2020 19;27(6):661-676. Epub 2020 Oct 19.

Pavia, Italy.

The increased risk of non-cardiovascular death in patients receiving clopidogrel or prasugrel in comparison with the placebo group in the Dual Antiplatelet Therapy (DAPT) trial in contrast to the decreased risk of cardiovascular death and all-cause death seen in patients treated with low-dose ticagrelor in the EU label population of the PEGASUS-TIMI 54 trial, resulted in inclusion in the 2020 ESC NSTE-ACS guidelines the recommendation for use of clopidogrel or prasugrel only if the patient is not eligible for treatment with ticagrelor. The prevalence of the primary outcome composed of cardiovascular death, stroke, or myocardial infarction was lower in the low-dose rivaroxaban and acetylsalicylic acid (ASA) group than in the ASA-alone group in the COMPASS trial. Moreover, all-cause mortality and cardiovascular mortality rates were lower in the rivaroxaban-plus-ASA group. Comparison of the PEGASUS-TIMI 54 and COMPASS trial patient characteristics clearly shows that each of these treatment strategies should be addressed at different groups of patients. A greater benefit in post-acute coronary syndrome (ACS) patients with a high risk of ischemic events and without high bleeding risk may be expected with ASA and ticagrelor 60 mg b.i.d. when the therapy is continued without interruption or with short interruption only after ACS. On the other hand, ASA and rivaroxaban 2.5 mg b.i.d. seems to be a better option when indications for dual antithrombotic therapy (DATT) appear after a longer time from ACS (more than 2 years) and/or from cessation of DAPT (more than 1 year) and in patients with multiple vascular bed atherosclerosis. Thus, both options of DATTs complement each other rather than compete, as can be presumed from the recommendations. However, a direct comparison between these strategies should be tested in future clinical trials.
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http://dx.doi.org/10.5603/CJ.a2020.0132DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8079117PMC
September 2021

Trends of Antithrombotic Treatment in Atrial Fibrillation Patients Undergoing Percutaneous Coronary Intervention: Insights from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) Registry.

Cardiovasc Drugs Ther 2021 02 9;35(1):11-20. Epub 2020 Oct 9.

2nd Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens Medical School, Rimini 1, Chaidari, 12462, Athens, Greece.

Purpose: Patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) are a high-risk subset of patients, whose optimal antithrombotic treatment strategy, involving a combination of anticoagulant and antiplatelet agents, has not been well defined. Our study aims to investigate contemporary "real-world" trends of antithrombotic treatment strategies in AF patients undergoing PCI, as well as identify factors affecting decision-making at hospital discharge.

Methods: "Real-world" data were retrieved from the GReek-AntiPlatElet Atrial Fibrillation (GRAPE-AF) registry, a contemporary, nationwide, multicenter, observational study of AF patients undergoing PCI. Characteristics of patients discharged on triple antithrombotic therapy (TAT) or dual antithrombotic therapy (DAT) were compared in order to identify factors that could influence treatment decisions.

Results: A total of 654 patients were enrolled (42% with stable coronary artery disease, 58% with acute coronary syndrome). TAT was adopted in 49.9% and DAT in 49.2% of patients at discharge. Regarding anticoagulants, the vast majority of patients (92.9%) received non-vitamin K antagonist oral anticoagulants (NOACs) and only 7.1% received vitamin K antagonists (VKAs). Dyslipidemia, insulin-dependent diabetes mellitus, prior myocardial infarction, acute coronary syndrome at presentation, and regional variations were predictive of TAT adoption, whereas the use of NOACs or ticagrelor was predictive of DAT adoption.

Conclusion: Contemporary "real-world" data concerning antithrombotic treatment in AF patients undergoing PCI indicate a strong shift towards the use of NOACs instead of VKAs, along with a large subset of patients adopting an aspirin-free strategy early after index PCI, with clinical as well as treatment characteristics affecting decision-making.

Trial Registration: ClinicalTrials.gov Identifier: NCT03362788 (First Posted: December 5, 2017).
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http://dx.doi.org/10.1007/s10557-020-07090-xDOI Listing
February 2021

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

Int J Cardiol 2020 Nov 26;318:1-6. Epub 2020 Jun 26.

Interventional Cardiology, University Clinic of Cardiology, Skopje, Macedonia.

Background: Acute myocardial infarction (AMI) recurrence is still high despite great progress in secondary prevention. Patients with recurrent AMI suffer worse prognosis compared to those with first AMI. The objective was to evaluate the effect of optimal medical therapy (OMT) on these patients with recurrent AMI.

Methods And Results: Sub-analysis was performed including 13,343 patients with AMI from the international multicenter Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome (BleeMACS) registry. OMT was defined as the combination of aspirin, any P2Y12 inhibitor, statin, angiotensin converting enzyme inhibitor/angiotensin receptor blocker, and beta-blocker. Among 1285 patients with prior AMI, 56.8% received OMT prescription. Patients receiving OMT suffered from less congestive heart failure, peripheral artery disease, malignancy, and bleeding history. Kaplan-Meier survival estimates revealed that OMT was strongly related to decreased in all-cause death (4.2% vs. 10.1%, p < .001) and the composite endpoint of death/re-AMI (11.1% vs. 16.9%, p = .005) at 1-year follow-up. OMT was the independent protect factor of primary endpoint even after adjusting for multiple possible confounders (HR, 0.46; 95% CI, 0.27-0.78; p = .004). However, no significant difference was observed regarding re-AMI between OMT and non-OMT groups. OMT also reduced all-cause death in patients with recurrent AMI after propensity score matching.

Conclusions: The prescription of OMT was seriously insufficient in patients with recurrent AMI, especially high-risk patients, even though OMT was associated with improved prognosis. Further improvements in pharmacological therapy are needed to reduce subsequent recurrent events.
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http://dx.doi.org/10.1016/j.ijcard.2020.06.021DOI Listing
November 2020

Global Longitudinal Strain of the Systemic Ventricle Is Correlated with Plasma Galectin-3 and Predicts Major Cardiovascular Events in Adult Patients with Congenital Heart Disease.

Medicina (Kaunas) 2020 Jun 22;56(6). Epub 2020 Jun 22.

Second Cardiology Department, ATTIKON University Hospital, National and Kapodistrian University of Athens, 12461 Athens, Greece.

: We sought to assess in adult congenital heart disease (ACHD) patients the prognostic value of plasma galectin-3 (Gal-3) levels and systemic ventricular global longitudinal strain (SV GLS) as well as their association with NTproBNP and arrhythmogenesis. : We studied 58 patients (26 men, mean age 37 ± 16.8 years) with various congenital heart diseases. Patients underwent echocardiogram, 24 h ambulatory ECG monitoring, while NTproBNP and Gal-3 were measured. They were followed up (median of 790.5 days -IQR 350.3 days) and major cardiovascular events (MACE) were recorded. . Mean Gal-3 levels were 17.07 ± 6.38 ng/m. Plasma Gal-3 was correlated with LogNTproBNP (r = 0.456, = 0.001).Gal-3 levels associated with supraventricular tachycardia (SVT) ( < 0.001) and ventricular tachycardia (VT) ( < 0.001), but was not associated with MACE (HR 1.018, 95% CI 0.944-1.098, = 0.641).Mean SVGLS in patients with systemic left ventricle was -15.91% ± 4.09%, which was significantly lower compared to patients with systemic right ventricle and patients with single ventricle (-11.42% ± 3.37% and -11.9% ± 5.06%, respectively, = 0.021).SV GLS correlated with plasma Gal-3 (r = 0.313, = 0.027) and logNTproBNP (r = 0.479, < 0.001). SVGLS correlated with VT arrhythmias ( = 0.004). NTproBNP predicted MACE (AUC 0.750, = 0.03). SVGLS also predicted MACE (AUC 0.745, = 0.03. In multivariate analysis, SVGLS and logNTproBNP maintained their predictive value ( = 0.004 and = 0.009, respectively) : In ACHD patients, SV GLS was found to predict MACE independently from NTproBNP and correlated with VT. Gal-3 correlated with NTproBNP and SVGLS as well as SVT and VT, but has not been shown to bear significant prognostic potential.
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http://dx.doi.org/10.3390/medicina56060305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7353898PMC
June 2020

Effect of Colchicine vs Standard Care on Cardiac and Inflammatory Biomarkers and Clinical Outcomes in Patients Hospitalized With Coronavirus Disease 2019: The GRECCO-19 Randomized Clinical Trial.

JAMA Netw Open 2020 06 1;3(6):e2013136. Epub 2020 Jun 1.

Department of Cardiology, Ioannina University Hospital, University of Ioannina, Ioannina, Greece.

Importance: Severe acute respiratory syndrome coronavirus 2 infection has evolved into a global pandemic. Low-dose colchicine combines anti-inflammatory action with a favorable safety profile.

Objective: To evaluate the effect of treatment with colchicine on cardiac and inflammatory biomarkers and clinical outcomes in patients hospitalized with coronavirus disease 2019 (COVID-19).

Design, Setting, And Participants: In this prospective, open-label, randomized clinical trial (the Greek Study in the Effects of Colchicine in COVID-19 Complications Prevention), 105 patients hospitalized with COVID-19 were randomized in a 1:1 allocation from April 3 to April 27, 2020, to either standard medical treatment or colchicine with standard medical treatment. The study took place in 16 tertiary hospitals in Greece.

Intervention: Colchicine administration (1.5-mg loading dose followed by 0.5 mg after 60 min and maintenance doses of 0.5 mg twice daily) with standard medical treatment for as long as 3 weeks.

Main Outcomes And Measures: Primary end points were (1) maximum high-sensitivity cardiac troponin level; (2) time for C-reactive protein to reach more than 3 times the upper reference limit; and (3) time to deterioration by 2 points on a 7-grade clinical status scale, ranging from able to resume normal activities to death. Secondary end points were (1) the percentage of participants requiring mechanical ventilation, (2) all-cause mortality, and (3) number, type, severity, and seriousness of adverse events. The primary efficacy analysis was performed on an intention-to-treat basis.

Results: A total of 105 patients were evaluated (61 [58.1%] men; median [interquartile range] age, 64 [54-76] years) with 50 (47.6%) randomized to the control group and 55 (52.4%) to the colchicine group. Median (interquartile range) peak high-sensitivity cardiac troponin values were 0.0112 (0.0043-0.0093) ng/mL in the control group and 0.008 (0.004-0.0135) ng/mL in the colchicine group (P = .34). Median (interquartile range) maximum C-reactive protein levels were 4.5 (1.4-8.9) mg/dL vs 3.1 (0.8-9.8) mg/dL (P = .73), respectively. The clinical primary end point rate was 14.0% in the control group (7 of 50 patients) and 1.8% in the colchicine group (1 of 55 patients) (odds ratio, 0.11; 95% CI, 0.01-0.96; P = .02). Mean (SD) event-free survival time was 18.6 (0.83) days the in the control group vs 20.7 (0.31) in the colchicine group (log rank P = .03). Adverse events were similar in the 2 groups, except for diarrhea, which was more frequent with colchicine group than the control group (25 patients [45.5%] vs 9 patients [18.0%]; P = .003).

Conclusions And Relevance: In this randomized clinical trial, participants who received colchicine had statistically significantly improved time to clinical deterioration. There were no significant differences in high-sensitivity cardiac troponin or C-reactive protein levels. These findings should be interpreted with caution.

Trial Registration: ClinicalTrials.gov Identifier: NCT04326790.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.13136DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7315286PMC
June 2020
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