Publications by authors named "Alexandros Briasoulis"

305 Publications

Catheter Ablation for Atrial Fibrillation in Patients with Heart Failure with Preserved Ejection Fraction: A Systematic Review and Meta-Analysis.

J Clin Med 2022 Jan 6;11(2). Epub 2022 Jan 6.

Electrophysiology Department, Barts Heart Centre, St. Bartholomew's Hospital, London EC1A 7BE, UK.

Background: Catheter ablation (CA) for atrial fibrillation (AF) has been proposed as a means of improving outcomes among patients with heart failure and reduced ejection fraction (HFrEF) who are otherwise receiving appropriate treatment. Unlike HFrEF, treatment options are more limited in patients with preserved ejection fraction (HFpEF) and the data pertaining to the management of AF in these patients are controversial. The aim of this systematic review and meta-analysis was to investigate the effects of CA on outcomes of patients with AF and HFpEF, such as functional status, post-procedural complications, hospitalization, morbidity and mortality, based on data from observational studies.

Methods: We systematically searched the electronic databases MEDLINE, PUBMED, EMBASE and the Cochrane Library for Central Register of Clinical Trials until May 2020.

Results: Overall, the pooling of our data showed that sinus rhythm was achieved long-term in 58.0% (95% CI 0.44-0.71). Long-term AF recurrence was noticed in 22.3% of patients. Admission for HF occurred in 6.2% (95% CI 0.04-0.09) whilst all-cause mortality was identified in 6.3% (95% CI 0.02-0.13).

Conclusion: This meta-analysis is the first to focus on determining the benefits of a rhythm control strategy for patients with AF and HFpEF using CA, suggesting it may be worthwhile to investigate the effects of a CA rhythm control strategy as the default treatment of AF in HFpEF patients in randomized trials.
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http://dx.doi.org/10.3390/jcm11020288DOI Listing
January 2022

Outcomes after heart transplantation in patients with cardiac sarcoidosis.

ESC Heart Fail 2022 Jan 15. Epub 2022 Jan 15.

Department of Cardiovascular Diseases, Mayo Clinic, Rochester, MN, USA.

Background: The number of patients with sarcoidosis requiring heart transplantation (HT) is increasing. The aim of this study was to evaluate outcomes of isolated HT in patients with sarcoid cardiomyopathy and compare them to recipients with non-ischaemic restrictive or dilated cardiomyopathy.

Methods And Results: Adult HT recipients were identified in the UNOS Registry between 1990 and 2020. Patients were grouped according to diagnosis. The cumulative incidences for the all-cause mortality and rejection were compared using Fine and Gray model analysis, accounting for re-transplantation as a competing risk. Rejection was evaluated using logistic regression analysis. We also reviewed characteristics and outcomes of all HT recipients with previous diagnosis of sarcoid cardiomyopathy from a single centre. A total of 30 160 HT recipients were included in the present study (n = 239 sarcoidosis, n = 1411 non-ischaemic restrictive cardiomyopathy, and n = 28 510 non-ischaemic dilated cardiomyopathy). During a total of 194 733 patient-years, all-cause mortality at the latest follow-up was not significantly different when comparing sarcoidosis to non-ischaemic dilated cardiomyopathy [adjusted subhazard ratio (aSHR) 1.46, 95% confidence intervals (CIs): 0.9-2.4, P = 0.12] or restrictive cardiomyopathy (aSHR 1.12, 95% CI: 0.65-1.95, P = 0.67). Accordingly, multivariable analysis suggested that 1 year mortality was not significantly different between sarcoidosis and non-ischaemic dilated cardiomyopathy (aSHR 1.56, 95% CI: 0.9-2.7, P = 0.12) or restrictive cardiomyopathy (aSHR 1.15, 95% CI: 0.61-2.18, P = 0.66). No differences were observed regarding 30 day mortality, treated and hospitalized acute rejection, and 30 day death from graft failure after HT. Thirty-day mortality did not improve significantly in more recent HT eras whereas there was a trend towards improved 1 year mortality in the latest HT era (P = 0.06). Data from the single-centre case review showed excellent long-term outcomes with sirolimus-based immunosuppression.

Conclusions: Short-term and long-term post HT outcomes among patients with sarcoid cardiomyopathy are similar to those with common types of non-ischaemic cardiomyopathy.
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http://dx.doi.org/10.1002/ehf2.13789DOI Listing
January 2022

Outcomes of diabetic patients with end-stage heart failure listed for heart transplantation: A propensity-matched analysis.

Clin Transplant 2022 Jan 12:e14590. Epub 2022 Jan 12.

Division of Heart Failure and Transplant, University of Iowa Hospitals and Clinics, Iowa, Iowa, USA.

Background: We investigated the current trends and outcomes of diabetic patients listed for heart transplants in the U.S. and provided a method for risk-stratification.

Methods: Using data from the United Network for Organ Sharing (UNOS), we identified heart failure patients listed for heart transplants between 2010 and 2019. Diabetic patients were propensity-matched with non-diabetics, and waitlist mortality as well as post-transplant graft survival were compared between the two groups. Further risk-stratification of diabetic patients was done based on the risk factors that independently predict graft failure.

Results: 28,928 adult patients (30% diabetic) with end-stage heart failure were added to the waitlist over the study period. In the propensity-matched cohort, waitlist mortality was higher in diabetic patients compared to non-diabetics (HR = 1.13 (95% CI = 1.04-1.22, P = .002). Over the study period, 5739 patients with diabetes were transplanted. In the propensity-matched cohorts of transplant recipients, the rate of graft failure was significantly higher for diabetic patients (23.3%) compared to non-diabetics (20.4%); HR = 1.17, 95% CI = 1.08-1.26, P < .001. We identified 12 risk factors of graft failure among diabetic patients and developed a risk score that further risk-stratify these patients. Diabetic patients at low risk (score≤4) had similar graft survival as patients without diabetes (HR = .91, 95% CI = .82-1.01, P = .06). On the other hand, high-risk diabetic patients had worse graft survival compared to non-diabetics (HR = 1.52, 95% CI = 1.38-1.67, P < .001).

Conclusion: Among patients with end-stage heart failure, pre-existing diabetes was associated with higher waitlist mortality and worse graft survival. However, with careful patient selection, graft survival is similar to those without diabetes.
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http://dx.doi.org/10.1111/ctr.14590DOI Listing
January 2022

Impact of atrial fibrillation on in-hospital outcomes among hospitalizations for cardiac surgery: an analysis of the National Inpatient Sample.

J Investig Med 2022 Jan 5. Epub 2022 Jan 5.

Division of Cardiology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA.

The short-term impact of atrial fibrillation (AF) on cardiac surgery hospitalizations has been previously reported in cohorts of various sizes, but results have been variable. Using the 2005-2014 National Inpatient Sample, we identified all adult hospitalizations for cardiac surgery using the International Classification of Diseases, Ninth Revision, Clinical Modification as any procedure code and AF as any diagnosis code. We estimated the impact of AF on inpatient mortality, length of stay (LOS), and cost of hospitalization using survey-weighted, multivariable logistic, accelerated failure-time log-normal, and log-transformed linear regressions, respectively. Additionally, we exact-matched AF to non-AF hospitalizations on various confounders for the same outcomes. A total of 1,269,414 hospitalizations were noted for cardiac surgery during the study period. Coexistent AF was found in 44.9% of these hospitalizations. Overall mean age was 65.6 years, 40.9% were female, mean LOS was 11.6 days, and inpatient mortality was 4.5%. Stroke rate was lower in AF hospitalizations (1.8% vs 2.1%, p<0.001). Mortality was lower in the AF (3.9%) versus the non-AF (5%) group (exact-matched OR or emOR=0.48, 95% CI 0.29 to 0.80, p<0.001; 987 matched pairs, n=2423), with similar results after procedural stratification: isolated valve replacement/repair (emOR=0.38, p<0.001), isolated coronary artery bypass graft (CABG) (emOR=0.33, p<0.001), and CABG with valve replacement/repair (emOR=0.55, p<0.001). A 12% increase was seen in LOS in the AF subgroup (exact-matched time ratio=1.12, 95% CI 1.10 to 1.14, p<0.001) among hospitalizations which underwent valve replacement/repair with or without CABG. Hospitalizations for cardiac surgery which had coexistent AF were found to have lower inpatient mortality risk and stroke prevalence but higher LOS and hospitalization costs compared with hospitalizations without AF.
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http://dx.doi.org/10.1136/jim-2021-001864DOI Listing
January 2022

Incidence and long-term outcome of heart transplantation patients who develop postoperative renal failure requiring dialysis.

J Heart Lung Transplant 2021 Nov 29. Epub 2021 Nov 29.

Division of Cardiovascular Medicine, Section of Heart Failure and Transplantation, University of Iowa, Iowa City, Iowa; National and Kapodistrian University of Athens, Athens, Greece. Electronic address:

Background: Acute renal failure requiring dialysis after heart transplantation remains a significant clinical issue because of its increasing incidence. We aimed to investigate its time trends, clinical predictors, and long-term outcomes.

Methods: Adult heart transplantation recipients registered in the United Network for Organ Sharing registry between 2009 and 2020 were identified. The patients were grouped according to the requirement for dialysis in the postoperative heart transplantation period. The independent risk predictors were identified, and the association between post-heart transplantation renal failure requiring dialysis and long-term mortality accounting for re-transplantation was investigated.

Results: A total of 28,170 patients were included in the study, of which 3,371 (12%) required dialysis immediately post-heart transplantation. The incidence increased from 7.9% to 13.9% during the study period. Longer ischemic time, serum creatinine at transplantation >1.2 mg/dL, prior cardiac surgery, higher recipient body mass index, support of mechanical ventilation or extracorporeal membrane oxygenation, and history of congenital heart disease or restrictive/hypertrophic cardiomyopathy were its predictors (all p < 0.05). Patients on posttransplant dialysis had a higher risk of all-cause mortality (adjusted hazard ratio [aHR]: 5.2, 95% CI: 4.7-5.7, p < 0.001), 30 day mortality (aHR: 7.7, 95% CI: 6.3-9.6, p < 0.001) and 1 year mortality (aHR: 7.5, 95% CI: 6.6-8.6, p < 0.001). Post-transplant dialysis was associated with a risk of treated rejection at 1 year.

Conclusion: Acute renal failure requiring dialysis after heart transplantation is associated with significantly worse 30 day and long-term mortalities, and thus, early identification of high-risk patients is crucial to prevent severe renal complications.
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http://dx.doi.org/10.1016/j.healun.2021.11.017DOI Listing
November 2021

The 30-day readmission rate of same-day discharge protocol following catheter ablation for atrial fibrillation: a propensity score-matched analysis from National Readmission Database.

Europace 2021 Dec 14. Epub 2021 Dec 14.

Division of Cardiology, Westchester Medical Center, Valhalla, NY, USA.

Aims: The effectiveness and safety of same-day discharge (SDD) for catheter ablation (CA) for atrial fibrillation (AF) has not been fully elucidated using a large nationwide database. This study aimed to evaluate the all-cause readmission rates within 30-days among patients receiving CA for AF with an SDD protocol compared with a conventional overnight stay (ONS).

Methods And Results: We performed a retrospective cohort study using the US Nationwide Readmission Database. The primary outcome was all-cause 30-day readmission following discharge in patients receiving CA and a secondary outcome was requiring total healthcare cost. A 1 : 3 propensity score matching was conducted to compare the safety and efficacy within both SDD and ONS group. Among 30 776 patients [mean 67.2 ± 11.4 years, 12 590 female (41.5%)] who received CA from 2016 through 2018, 440 (1.42%) patients were discharged on the same-day following CA (SDD group), and the remaining 30 336 patients stayed at least one night in the hospital (ONS group). A propensity score analysis generated 1751 matched pairs (440 in the SDD group; 1311 in the ONS group). The 30-day readmission following discharge was not significantly higher in the SDD group than the ONS group (SDD vs. ONS: 12.7% vs. 9.7%; hazard ratio: 1.17, 95% confidence interval: 0.76-1.81, P = 0.47). Healthcare cost was significantly higher in the ONS group ($25 237 ± 14 036 vs. $30 749 ± 16 383; P < 0.01).

Conclusion: In this nationwide database study, there was no significant difference in the all-cause 30-day readmission following SDD for CA compared with ONS.
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http://dx.doi.org/10.1093/europace/euab296DOI Listing
December 2021

Trends and outcomes of opioid-related cardiac arrest in a contemporary US population.

Eur J Intern Med 2021 Nov 16. Epub 2021 Nov 16.

Division of Cardiovascular Medicine, University of Iowa Hospitals and Clinics & National Kapodistrian University of Athens, Greece. Electronic address:

Background: Opioid abuse is a worldwide public health issue, and deaths related to opioid abuse are increasing. We aimed to investigate trends, predictors, and outcomes of cardiac arrest in patients with opioid abuse.

Methods: All hospitalizations for primary diagnosis of cardiac arrest between 2012 and 2018 identified in the Nationwide Inpatient Sample were categorized into those with or without a secondary diagnosis of opioid overdose. Multivariable logistic regression was used to analyze in-hospital outcomes of opioid-associated cardiac arrest after adjusting for patient and hospital characteristics.

Results: Among 1,410,475 hospitalizations with cardiac arrest, opiate abuse as a secondary diagnosis was found in 3.1% (n=43,090) of hospitalizations, with an increasing trend during the study period. Hospitalizations for cardiac arrest with opioid abuse were seen less likely in patients with heart failure (21.2% vs. 40.6%; p<0.05), diabetes mellitus (19.5% vs. 35.4%; p<0.05), hypertension (43.4% vs. 64.9%; p<0.05) and renal failure (14.3% vs. 30.2%; p<0.05) and more frequently in those with history of alcohol abuse (16.9% vs. 7.1%; p<0.05), depression (18.8% vs. 9%; p<0.05), and smoking (37.0% vs. 21.8%; p<0.05) as compared with cardiac arrest without opioid use. In-hospital mortality in cardiac arrest patients with and without opioids was not different after multivariable adjustment (odds ratio OR 0.96, 0.91-1.00; p=0.07). OA-OHCA was associated with significantly higher risks of acute kidney injury, acute respiratory failure, and mechanical ventilation, p<0.05 for all.

Conclusion: Opioid abuse remains a significant cause of cardiac arrest. Despite similar in-hospital mortality and lower resource utilization, severe complications are more frequent in opioid abuse related cardiac arrests compared to those without opioid abuse.
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http://dx.doi.org/10.1016/j.ejim.2021.11.004DOI Listing
November 2021

Safety and efficacy of cerebral embolic protection devices in patients undergoing transcatheter aortic valve replacement: a meta-analysis of in-hospital outcomes.

Cardiovasc Interv Ther 2021 Nov 13. Epub 2021 Nov 13.

Section of Heart Failure and Transplant, Division of Cardiovascular Diseases, University of Iowa Hospitals and Clinics, 200 Hawkins Dr, Iowa City, IA, 52242, USA.

The evidence regarding the impact of cerebral embolic protection devices (EPDs) on outcomes following transcatheter aortic valve replacement (TAVR) is limited. The objective of this study was to evaluate in-hospital outcomes with the use of cerebral EPDs in TAVR. We performed a comprehensive EMBASE and PUBMED search to investigate randomized control studies or propensity score-matched retrospective studies which assessed patients undergoing TAVR with or without EPD up to April 2021. Endpoints of interest were in-hospital mortality, stroke, acute kidney injury, pacemaker implantation, major bleeding, vascular complication, length of stay. Ten studies involving 173,002 patients with EPD (n = 16,898, 9.8%) and those without (n = 156,104, 90.2%) fulfilled the inclusion criteria. The use of EPD was associated with significantly lower risk of in-hospital stroke (odds ratio [95% confidential interval]: 0.64 [0.46; 0.89]), but similar rate of in-hospital mortality (odds ratio [95% confidential interval]: 0.75 [0.54; 1.05]). No differences were observed in acute kidney injury, pacemaker implantation, major bleeding, vascular complication, length of stay. EPD during TAVR was associated with lower in-hospital stroke but did not affect procedural complications and length of stay.
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http://dx.doi.org/10.1007/s12928-021-00823-1DOI Listing
November 2021

National Trends in Heart Failure Hospitalization and Readmissions Associated With Policy Changes.

JAMA Cardiol 2022 Jan;7(1):114

Division of General Internal Medicine and Health Services Research, David Geffen School of Medicine at UCLA, University of California, Los Angeles.

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http://dx.doi.org/10.1001/jamacardio.2021.4416DOI Listing
January 2022

Immunological Response to COVID-19 Vaccination in Ovarian Cancer Patients Receiving PARP Inhibitors.

Vaccines (Basel) 2021 Oct 8;9(10). Epub 2021 Oct 8.

Department of Clinical Therapeutics, School of Medicine, Alexandra General Hospital, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Objective: Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, limited data exist for cancer patients under systemic therapy.

Methods: In this cohort, we prospectively enrolled cancer patients treated with PARPi as well as healthy volunteers in order to study the kinetics of anti-SARS-CoV-2 antibodies (NAbs) after COVID-19 vaccination. Baseline demographics, co-morbidities, and NAb levels were compared between the two groups.

Results: The results of the cohort of 36 patients receiving PARP inhibitors are presented here. Despite no new safety issues being noticed, their levels of SARS-CoV-2 neutralizing antibodies were significantly lower in comparison to matched healthy volunteers up to day 30 after the second dose.

Conclusions: These results suggest that maintaining precautions against COVID-19 is essential for cancer patients and should be taken into consideration for the patients under treatment, while further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.
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http://dx.doi.org/10.3390/vaccines9101148DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8541338PMC
October 2021

Changing Demographics, Temporal Trends in Waitlist, and Posttransplant Outcomes After Heart Transplantation in the United States: Analysis of the UNOS Database 1991-2019.

Circ Heart Fail 2021 11 25;14(11):e008764. Epub 2021 Oct 25.

Division of Heart Failure and Transplant (A.B.), University of Iowa Hospitals and Clinics, Iowa City.

Background: We sought to investigate temporal trends in patient characteristics, waitlist, and posttransplant outcomes after heart transplantation in the United States.

Methods: Using data from the United Network of Organ Sharing, we identified adults listed for heart transplantation between 1991 and 2019. Patients were divided into 4 eras based on the 3 time points in which changes were made to the patient selection/allocation policy (Era 1=January 1991-January 1999; Era 2=January 1999-July 2006; Era 3=July 2006-October 2018; and Era 4=October 2018-March 2020), and patient characteristics, waitlist, and posttransplant outcomes were evaluated for each era.

Results: Between 1991 and 2019, 95 179 patients were added to the heart transplantation waitlist. Compared with Era 1, patients listed in Era 4 were older (mean age: 50 versus 52 years) and with higher risk comorbidities (eg, 10% versus 28.8% diabetes, 23.3% versus 35.6% obese). Over the study period, 22 738 patients died or were permanently delisted for deterioration on the waitlist while 61 687 were transplanted. Compared with the preceding era, there was significant decrease in death or deterioration in the last 2 eras (sub-hazard ratio, 0.67 [95% CI, 0.65-0.70] for Era 3 versus Era 2 and sub-hazard ratio, 0.65 [95% CI, 0.58-0.73] for Era 4 versus 3). Across the years, 27.1% to 40.5% of those on the waitlist were transplanted. Among those transplanted, there was increase in the rates of in-hospital stroke (2.8% in Era 1 to 3.7% in Era 4), renal failure requiring dialysis (7.2%-17.1%), and length-of-stay (14-17days), <0.001. However, this did not negatively impact short-term survival when compared with the preceding era (1-year graft survival from Era 1 to Era 4=84.1%, 86.4%, 90.4%, and 89.7%, respectively).

Conclusions: There have been significant changes in the characteristics of patients listed for heart transplantation. Although transplant volume has increased, the wide supply-demand gap persisted. The last two changes in the allocation policy achieved their primary objective of reducing waitlist mortality.
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http://dx.doi.org/10.1161/CIRCHEARTFAILURE.121.008764DOI Listing
November 2021

Conventional sternotomy versus right mini-thoracotomy versus robotic approach for mitral valve replacement/repair; insights from a network meta-analysis.

J Cardiovasc Surg (Torino) 2021 Oct 19. Epub 2021 Oct 19.

Department of Surgery, The University of Chicago Medicine, Chicago, IL, USA.

Objective: Minimally invasive cardiac surgery (MICS) through right mini-thoracotomy as well as robotic surgery has emerged for the last decade for mitral valve surgery. However, their risks and benefits are not fully understood yet. Thus, we conducted a network meta-analysis comparing the early- and long-term outcomes of mitral valve surgery via the conventional sternotomy, MICS, and robotic approaches.

Evidence Acquisition: MEDLINE and EMBASE were searched through November, 2020 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) trials that investigated early- and long-term outcomes after mitral surgery via the conventional sternotomy, MICS, and robotic approaches. A subalalysis focusing on only subjects who initially underwent mitral valve repair was also conducted.

Evidence Synthesis: Our systematic literature search identified 2 RCTs and 19 PSM studies. MICS was related to significant risk reductions of permanent pacemaker implantation, surgical site infection, and transfusion compared to the sternotomy approach. The robotic approach was associated with a significant increase in re-exploration for bleeding compared to sternotomy. The subanalysis showed that MICS was associated with a significant increase requiring mitral valve reoperation compared to the sternotomy approach (hazard ratio [95% confidence interval] =7.33 [1.54-34.97], p=0.012), while no significant difference was observed between the sternotomy and the robotic approach.

Conclusions: Our network meta-analysis demonstrated that MICS was associated with better short-term outcomes compared to the sternotomy approach. Mitral valve reoperation was more frequent with MICS compared with the sternotomy approach after mitral valve repair, while no difference was observed between the sternotomy and robotic approaches.
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http://dx.doi.org/10.23736/S0021-9509.21.11902-0DOI Listing
October 2021

Comparative Safety and Effectiveness of Loading Doses of P2Y12 Inhibitors in Patients Undergoing Elective PCI: a Network Meta-analysis.

Cardiovasc Drugs Ther 2021 Oct 13. Epub 2021 Oct 13.

Lehigh Valley Heart Institute, Lehigh Valley Health Network, Allentown, PA, USA.

Purpose: Effective platelet inhibition prior to elective percutaneous coronary intervention (PCI) reduces the risk of ischemic complications. Newer P2Y12 inhibitors are preferred agents over clopidogrel for patients presenting with the acute coronary syndrome. However, the comparative efficacy and safety of them over clopidogrel in elective PCI is unclear. We performed a network meta-analysis to compare the safety and efficacy of loading strategies of P2Y12 inhibitors in patients undergoing elective PCI.

Methods: We conducted a systematic review of randomized controlled trials (RCT) up to June 2021 to compare the safety and effectiveness of different loading strategies of P2Y12 inhibitors before elective PCI. The endpoints of interest were overall mortality, rates of myocardial infarction (MI), stroke, revascularization, and major bleeding. Random effects model using the frequentist approach was used to perform a network meta-analysis using R software.

Results: Five trials with a total of 5194 patients were included in our analysis. For ischemic outcomes, including MI, stroke, and revascularization, prasugrel had the most favorable trend. However, clopidogrel had the highest probability of being most effective for major bleeding and all-cause mortality. None of these trends was statistically significant due to lack of power for each outcome.

Conclusion: Although prasugrel and ticagrelor are known as more potent antiplatelet agents, their effects in preventing MI and stroke are marginal and do not translate into improved overall mortality and bleeding compared with clopidogrel.
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http://dx.doi.org/10.1007/s10557-021-07270-3DOI Listing
October 2021

Treatment with abiraterone or enzalutamide does not impair immunological response to COVID-19 vaccination in prostate cancer patients.

Prostate Cancer Prostatic Dis 2021 Oct 9. Epub 2021 Oct 9.

Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.

Data regarding the safety and efficacy of COVID-10 vaccines among cancer patients are lacking. Factors such as age, underlying disease and antineoplastic treatment confer negatively to the immune response due to vaccination. The degree of immunosuppression though may be lessen by targeted treatments like the androgen receptor-targeted agents (ARTA) that are commonly used in patients with metastatic prostate cancer. Herein, we report our data on 25 patients with prostate cancer under treatment with ARTA who were vaccinated for COVID-19. Our data suggest that these patients develop neutralizing antibodies against SARS-CoV-2 similarly to healthy volunteers. No safety issues were noted.
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http://dx.doi.org/10.1038/s41391-021-00455-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8501917PMC
October 2021

Utilization and tolerance of beta-blockers among patients with AL amyloidosis.

Amyloid 2021 Sep 22:1-7. Epub 2021 Sep 22.

Department of Clinical Therapeutics, National Kapodistrian University of Athens, Medical School, Athens, Greece.

Background: The utilization and clinical impact of beta-blockers (BBs) in cardiac amyloidosis (CA) is largely unexplored.

Methods: We conducted a retrospective, single-center analysis of indications, timing of initiation, types and doses of BB used, reasons to discontinue BB and association between BB tolerance and outcomes in a cohort of patients with immunoglobulin light chain amyloidosis (AL).

Results: We reviewed 236 patients with AL CA and identified 53 patients taking BB (22.5%). Most patients presented in New York Heart Association Class (NYHA) II or III (74.5%) and 24% presented in Mayo stage IIIB. The most frequent indications for BB initiation were atrial fibrillation (AF) and coronary artery disease (CAD). In most cases (59%) BB was started before the diagnosis of CA. The median duration of BB treatment was 9 months (interquartile range [IQR] 3-24 months). Among patients receiving BB, 28 tolerated BB during follow-up whereas 25 patients discontinued BB. The main causes of BB discontinuation were hypotension and heart failure (HF) exacerbation. Patients intolerant to BB presented with more advanced NYHA class, worse performance status and lower median left ventricular ejection fraction (LVEF) at baseline. At median follow-up duration of 17.7 months, patients who did not tolerate BB had a poor survival.

Conclusions: Although some patients with CA may have indications for treatment with BB, their use is uncommon and those with more advanced disease tolerate BB poorly. Intolerance to BB in patients with cardiac AL is an indicator of poorer outcome.
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http://dx.doi.org/10.1080/13506129.2021.1981281DOI Listing
September 2021

Poor neutralizing antibody responses in 106 patients with WM after vaccination against SARS-CoV-2: a prospective study.

Blood Adv 2021 11;5(21):4398-4405

Department of Clinical Therapeutics, School of Medicine, and.

Immunocompromised patients with hematologic malignancies are more susceptible to COVID-19 and at higher risk of severe complications and worse outcomes compared with the general population. In this context, we evaluated the humoral response by determining the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 in patients with Waldenström macroglobulinemia (WM) after vaccination with the BNT162b2 or AZD1222 vaccine. A US Food and Drug Administration-approved enzyme-linked immunosorbent assay-based methodology was implemented to evaluate NAbs on the day of the first vaccine shot, as well as on days 22 and 50 afterward. A total of 106 patients with WM (43% men; median age, 73 years) and 212 healthy controls (46% men; median age, 66 years) who were vaccinated during the same period at the same center were enrolled in the study (which is registered at www.clinicaltrials.gov as #NCT04743388). Our data indicate that vaccination with either 2 doses of the BNT162b2 or 1 dose of the AZD1222 vaccine leads to lower production of NAbs against SARS-CoV-2 in patients with WM compared with controls on days 22 and 50 (P < .001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with either rituximab or Bruton's tyrosine kinase inhibitors was proven as an independent prognostic factor for suboptimal antibody response after vaccination. In conclusion, patients with WM have low humoral response after COVID-19 vaccination, which underlines the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.
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http://dx.doi.org/10.1182/bloodadvances.2021005444DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8450138PMC
November 2021

Myeloma patients with COVID-19 have superior antibody responses compared to patients fully vaccinated with the BNT162b2 vaccine.

Br J Haematol 2022 01 16;196(2):356-359. Epub 2021 Sep 16.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Greece.

Patients with multiple myeloma (MM) have a suboptimal antibody response following vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and lower seroconversion rates following coronavirus disease 2019 (COVID-19) compared with healthy individuals. In this context, we evaluated the development of neutralising antibodies (NAbs) against SARS-CoV-2 in non-vaccinated patients with MM and COVID-19 compared with patients after vaccination with two doses of the BNT162b2 vaccine. Serum was collected either four weeks post confirmed diagnosis or four weeks post a second dose of BNT162b2. NAbs were measured with a Food and Drug Administration-approved enzyme-linked immunosorbent assay methodology. Thirty-five patients with COVID-19 and MM along with 35 matched patients were included. The two groups did not differ in age, sex, body mass index, prior lines of therapy, disease status, lymphocyte count, immunoglobulin levels and comorbidities. Patients with MM and COVID-19 showed a superior humoral response compared with vaccinated patients with MM. The median (interquartile range) NAb titre was 87·6% (71·6-94%) and 58·7% (21·4-91·8%) for COVID-19-positive and vaccinated patients, respectively (P = 0·01).Importantly, there was no difference in NAb production between COVID-19-positive and vaccinated patients who did not receive any treatment (median NAb 85·1% vs 91·7%, P = 0·14). In conclusion, our data indicate that vaccinated patients with MM on treatment without prior COVID-19 should be considered for booster vaccine doses.
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http://dx.doi.org/10.1111/bjh.17841DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8653218PMC
January 2022

Poor Neutralizing Antibody Responses in 132 Patients with CLL, NHL and HL after Vaccination against SARS-CoV-2: A Prospective Study.

Cancers (Basel) 2021 Sep 6;13(17). Epub 2021 Sep 6.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, 11528 Athens, Greece.

Emerging data suggest suboptimal antibody responses to COVID-19 vaccination in patients with hematological malignancies. We evaluated the humoral response following the BNT162b2 vaccine in patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), and Hodgkin's lymphoma (HL). An FDA-approved, ELISA-based methodology was implemented to evaluate the titers of neutralizing antibodies (NAbs) against SARS-CoV-2 on day 1 of the first vaccine, and afterwards on day 22 and 50. One hundred and thirty-two patients with CLL/lymphomas and 214 healthy matched controls vaccinated during the same period, at the same center were enrolled in the study (NCT04743388). Vaccination with two doses of the BNT162b2 vaccine led to lower production of NAbs against SARS-CoV-2 in patients with CLL/lymphomas compared with controls both on day 22 and on day 50 ( < 0.001 for all comparisons). Disease-related immune dysregulation and therapy-related immunosuppression are involved in the low humoral response. Importantly, active treatment with Rituximab, Bruton's tyrosine kinase inhibitors, or chemotherapy was an independent prognostic factor for suboptimal antibody response. Patients with HL showed superior humoral responses to the NHL/CLL subgroups. In conclusion, patients with CLL/lymphomas have low humoral response following COVID-19 vaccination, underlining the need for timely vaccination ideally during a treatment-free period and for continuous vigilance on infection control measures.
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http://dx.doi.org/10.3390/cancers13174480DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8430746PMC
September 2021

SARS-CoV-2 neutralizing antibodies after first vaccination dose in breast cancer patients receiving CDK4/6 inhibitors.

Breast 2021 Dec 28;60:58-61. Epub 2021 Aug 28.

Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Alexandra General Hospital, Athens, Greece.

Undoubtedly, the development of COVID-19 vaccines displays a critical step towards ending this devastating pandemic, considering their protective benefits in the general population. Yet, data regarding their efficacy and safety in cancer patients are limited. Herein we provide the initial analysis of immune responses after the first dose of vaccination in 21 breast cancer patients receiving cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors. The levels of neutralizing antibodies post vaccination were similar to the matched healthy controls, whereas no safety issues have been raised. Further exploration is needed to reduce the uncertainty of SARS-CoV-2 immunity among cancer patients under treatment.
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http://dx.doi.org/10.1016/j.breast.2021.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8402928PMC
December 2021

Trends, risk factors, and outcomes of post-operative stroke after heart transplantation: an analysis of the UNOS database.

ESC Heart Fail 2021 10 25;8(5):4211-4217. Epub 2021 Aug 25.

National Kapodistrian University of Athens Medical School, Athens, Greece.

Background: Post-operative stroke increases morbidity and mortality after cardiac surgery. Data on characteristics and outcomes of stroke after heart transplantation (HTx) are limited.

Methods And Results: We conducted a retrospective analysis of the United Network for Organ Sharing (UNOS) database from 2009 to 2020 to identify adults who developed stroke after orthotropic HTx. Heart transplant recipients were divided according to the presence or absence of post-operative stroke. The primary endpoint was all-cause mortality. A total of 25 015 HT recipients were analysed, including 719 (2.9%) patients who suffered a post-operative stroke. The stroke rates increased from 2.1% in 2009 to 3.7% in 2019, and the risk of stroke was higher after the implantation of the new allocation system [odds ratio 1.29, 95% confidence intervals (CI) 1.06-1.56, P = 0.01]. HTx recipients with post-operative stroke were older (P = 0.008), with higher rates of prior cerebrovascular accident (CVA) (P = 0.004), prior cardiac surgery (P < 0.001), longer waitlist time (P = 0.04), higher rates of extracorporeal membrane oxygenation (ECMO) support (P < 0.001), left ventricular assist devices (LVADs) (P < 0.001), mechanical ventilation (P = 0.003), and longer ischaemic time (P < 0.001). After multivariable adjustment for recipient and donor characteristics, age, prior cardiac surgery, CVA, support with LVAD, ECMO, ischaemic time, and mechanical ventilation at the time of HTx were independent predictors of post-operative stroke. Stroke was associated with increased risk of 30 day and all-cause mortality (hazard ratio 1.49, 95% CI 1.12-1.99, P = 0.007).

Conclusions: Post-operative stroke after HTx is infrequent but associated with higher mortality. Redo sternotomy, LVAD, and ECMO support at HTx are among the risk factors identified.
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http://dx.doi.org/10.1002/ehf2.13562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8497374PMC
October 2021

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and bioprosthetic valves: A meta-analysis.

J Thorac Cardiovasc Surg 2021 Jul 29. Epub 2021 Jul 29.

Department of Cardiology, Montefiore Medical Center, Albert Einstein Medical College, New York, NY. Electronic address:

Background: The optimal anticoagulation strategy for patients with bioprosthetic valves and atrial fibrillation remains uncertain. We conducted a meta-analysis using updated evidence comparing direct anticoagulants (DOACs) and vitamin K antagonists (VKAs) in patients with bioprosthetic valves and atrial fibrillation.

Methods: Medline and Embase were searched through March 2021 to identify randomized controlled trials (RCTs) and observational studies investigating the outcomes of DOAC therapy and VKA therapy in patients with bioprosthetic valves and atrial fibrillation. The outcomes of interest were all-cause death, major bleeding, and stroke or systemic embolism.

Results: Our analysis included 4 RCTs and 6 observational studies enrolling a total of 6405 patients with bioprosthetic valves and atrial fibrillation assigned to a DOAC group (n = 2142) or a VKA group (n = 4263). Pooled analysis demonstrated the similar rates of all-cause death (hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .18; I = 0%) in the DOAC and VKA groups. However, the rate of major bleeding was significantly lower in the DOAC group (HR, 0.66; 95% CI, 0.48-0.89; P = .006; I = 0%), whereas the rate of stroke or systemic embolism was similar in the 2 groups (HR, 0.72; 95% CI, 0.44-1.17; P = .18; I = 39%).

Conclusions: DOAC might decrease the risk of major bleeding without increasing the risk of stroke or systemic embolism or all-cause death compared with VKA in patients with bioprosthetic valves and atrial fibrillation.
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http://dx.doi.org/10.1016/j.jtcvs.2021.07.034DOI Listing
July 2021

SARS-CoV-2 Viral Load and Myocardial Injury: Independent and Incremental Predictors of Adverse Outcome.

Mayo Clin Proc Innov Qual Outcomes 2021 Oct 13;5(5):891-897. Epub 2021 Aug 13.

Division of Cardiology, Wayne State University, Detroit, MI.

To evaluate the association of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) initial viral load (iVL) and the incidence of myocardial injury (MCI) in hospitalized patients with SARS-CoV-2 infection, we conducted a retrospective longitudinal study of hospitalized patients who had a nasopharyngeal swab sample on admission that returned a positive result for SARS-CoV-2 by polymerase chain reaction between April 4 and June 5, 2020. The cycle threshold (Ct) value was used as a surrogate for the iVL level, with a Ct level of 36 or less for elevated iVL and greater than 36 for low iVL. Myocardial injury was defined as an elevated high-sensitivity cardiac troponin I level that was higher than the 99th percentile upper reference limit. A total of 270 patients were included. Of these, 171 (63.3%) had an elevated iVL and 88 (32.6%) had MCI. There was no significant difference in the incidence of MCI in patients with low iVL compared to those with elevated iVL (28 of 99 [28.3%] vs 60 of 171 [35.1%]; =.25). In a multivariable model, MCI (odds ratio, 3.86; 95% CI, 1.80 to 8.34; <.001) and elevated iVL (odds ratio, 4.21; 95% CI, 2.06 to 8.61; <.001) were independent and incremental predictors of in-hospital mortality. The SARS-CoV-2 iVL level is not associated with increased incidence of MCI, although both parameters are strong independent and incremental predictors of mortality. Understanding the MCI mechanisms allows for early focused interventions to improve survival, especially in patients with SARS-CoV-2 infection and high iVL.
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http://dx.doi.org/10.1016/j.mayocpiqo.2021.08.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8360996PMC
October 2021

Analysis of outcome of 6-month readmissions after percutaneous left atrial appendage occlusion.

Heart 2021 Aug 16. Epub 2021 Aug 16.

Cardiovascular Diseases, University of Iowa, Iowa City, Iowa, USA.

Objective: Percutaneous left atrial appendage occlusion (LAAO) is an alternative strategy for prevention of thromboembolic events in patients with atrial fibrillation and unsuitable for long-term oral anticoagulation. The study aimed to evaluate the causes and timing of readmissions within 6 months following percutaneous LAAO in a real-world setting.

Methods: We conducted a retrospective cohort study of percutaneous LAAO performed in the USA between January and June of 2016-2018 using the Nationwide Readmissions Database.

Results: Overall, 12 446 patients who underwent LAAO were included in the analyses and 3477 patients (28%) were readmitted within 6 months following the interventions. Readmitted patients were more often women (p=0.001). The index hospitalisation was characterised by longer duration of hospital stay (p<0.001) and complicated with acute kidney injury (p<0.001) among readmitted patients compared with those without readmissions. Readmissions within 6 months following the index intervention were mainly due to heart failure (13%) and gastrointestinal bleeding (12%). Characteristics associated with readmissions due to heart failure included previously known heart failure (HR 2.39; 95% CI 1.70 to 3.37), valvular heart disease (HR 1.39; 95% CI 1.05 to 1.84) and chronic kidney disease (HR 1.42; 95% CI 1.03 to 1.94). Readmissions due to gastrointestinal bleeding were associated with diabetes mellitus (HR 1.78; 95% CI 1.25 to 2.53), chronic kidney disease (HR 1.86; 95% CI 1.23 to 2.81) and previous anaemia (HR 2.41; 95% CI 1.54 to 3.77).

Conclusions: After percutaneous LAAO, over a quarter of the patients in the USA required rehospitalisation within 6 months, mainly due to heart failure and gastrointestinal bleeding.
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http://dx.doi.org/10.1136/heartjnl-2021-319345DOI Listing
August 2021

Risk of Ischemic Stroke in Transcatheter Aortic Valve Implantation Versus Surgical Aortic Valve Replacement in Patients With Prior Stroke.

Am J Cardiol 2021 10 6;157:79-84. Epub 2021 Aug 6.

Division of Cardiology, Westchester Medical Center and New York Medical College, Valhalla, New York.

It has not been well studied whether transcatheter aortic valve implantation (TAVI) or surgical aortic valve replacement (SAVR) have lower risk of ischemic stroke (IS) in those with prior history of IS. From the Nationwide Readmission Database from October 2015 to November 2017, TAVI and SAVR above age 50 were identified with the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System codes. Transapical TAVI and SAVR with concomitant bypass, mitral, or tricuspid surgery were excluded. The primary outcome was in-hospital IS. A total of 92,435 TAVI (13,292 with prior stroke) and 68,651 SAVR (5,365 with prior stroke) were identified. In-hospital IS was significantly lower in TAVI compared with SAVR (3.7% vs 8.0%, adjusted odds ratio 0.65, 95% confidence interval 0.47 to 0.89, p <0.01) with prior stroke whereas it was similar between TAVI and SAVR (1.7% vs 2.1%, adjusted odds ratio 0.97, 95% confidence interval 0.78 to 1.19, p = 0.75) in those without prior stroke (P < 0.001). In-hospital mortality, acute kidney injury, and bleeding were lower in TAVI compared with SAVR in patients with and without prior stroke (P > 0.05 for all). This analysis of a national claims database showed that TAVI was associated with a lower risk of in-hospital IS compared with SAVR among patients with prior stroke.
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http://dx.doi.org/10.1016/j.amjcard.2021.06.049DOI Listing
October 2021

Prognostic Implications of Ambulatory N-Terminal Pro-B-Type Natriuretic Peptide Changes in Patients with Continuous-Flow Left Ventricular Assist Devices.

ASAIO J 2021 Aug 3. Epub 2021 Aug 3.

From the Department of Medicine, University of Iowa Health Care, Carver College of Medicine, Iowa, Iowa Department of Medicine, University at Buffalo, Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York Department of Surgery, University of Iowa Health Care, Carver College of Medicine, Iowa, Iowa.

Data regarding the role of N-terminal Pro-B-type natriuretic peptide (NT-pro BNP) in patients with a continuous-flow left ventricular assist device (CFLVAD) is scarce. To evaluate the prognostic implications of measuring both absolute values and changes in NT-pro BNP concentrations in ambulatory patients with a CFLVAD, we performed a retrospective study of 168 consecutive patients who had an LVAD implantation at our institution and survived beyond their index hospitalization. Of these, 127 patients (56.2 ± 12.5 years, 21.2% female) had NT-pro BNP measured at 1 and 3 months postdischarge in ambulatory settings. Compared to the NT-pro BNP concentration at 1 month, 94 patients (74%) had a decline, and 33 patients (26%) had an increase in concentrations, from their 1 month baseline. After a median follow-up of 17 months, a total of 53 (41.7%) adverse events occurred. Of these, 37 (69.8%) were heart failure (HF) hospitalizations, and 16 (30.2%) were deaths. For each 1,000 unit increase in NT-pro BNP concentration at 3 months, there was a 17% increase in the risk of HF hospitalization or death (hazard ratio [HR] = 1.17, 95% confidence interval [CI] = 1.04-1.32, p = 0.007). Conversely, each 1000 unit decline during the same time, was associated with an 11% decrease in the risk of HF hospitalization or death (HR = 0.89, 95% CI = 0.77-0.98, p = 0.04). In conclusion, in patients with a CFLAD, an increase in NT-pro BNP concentration from 1 to 3 months is associated with an increased risk of HF hospitalization and death. In contrast, a decline is associated with a reduction in the risk of HF hospitalization and death.
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http://dx.doi.org/10.1097/MAT.0000000000001524DOI Listing
August 2021

The neutralizing antibody response post COVID-19 vaccination in patients with myeloma is highly dependent on the type of anti-myeloma treatment.

Blood Cancer J 2021 08 2;11(8):138. Epub 2021 Aug 2.

Department of Clinical Therapeutics, School of Medicine, National and Kapodistrian University of Athens, Athens, Greece.

Recent data suggest a suboptimal antibody response to COVID-19 vaccination in patients with hematological malignancies. Neutralizing antibodies (NAbs) against SARS-CoV-2 were evaluated in 276 patients with plasma cell neoplasms after vaccination with either the BNT162b2 or the AZD1222 vaccine, on days 1 (before the first vaccine shot), 22, and 50. Patients with MM (n = 213), SMM (n = 38), and MGUS (n = 25) and 226 healthy controls were enrolled in the study (NCT04743388). Vaccination with either two doses of the BNT162b2 or one dose of the AZD1222 vaccine leads to lower production of NAbs in patients with MM compared with controls both on day 22 and on day 50 (p < 0.001 for all comparisons). Furthermore, MM patients showed an inferior NAb response compared with MGUS on day 22 (p = 0.009) and on day 50 (p = 0.003). Importantly, active treatment with either anti-CD38 monoclonal antibodies (Mabs) or belantamab mafodotin and lymphopenia at the time of vaccination were independent prognostic factors for suboptimal antibody response following vaccination. In conclusion, MM patients have low humoral response following SARS-CoV-2 vaccination, especially under treatment with anti-CD38 or belamaf. This underlines the need for timely vaccination, possibly during a treatment-free period, and for continuous vigilance on infection control measures in non-responders.
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http://dx.doi.org/10.1038/s41408-021-00530-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8327056PMC
August 2021

The Utility of Non-LGE Cardiac Magnetic Resonance Imaging Parameters in the Diagnosis of Cardiac Amyloidosis.

Heart Lung Circ 2021 Dec 30;30(12):e137-e138. Epub 2021 Jul 30.

Department of Clinical Therapeutics, National Kapodistrian University of Athens, Medical School, Athens, Greece.

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http://dx.doi.org/10.1016/j.hlc.2021.07.007DOI Listing
December 2021

Network meta-analysis of treatment strategies in patients with coronary artery disease and low left ventricular ejection fraction.

J Card Surg 2021 Oct 26;36(10):3834-3842. Epub 2021 Jul 26.

Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York City, New York, USA.

Objective: The optimal treatment strategy in patients with coronary artery disease (CAD) and low left ventricular ejection fraction (LVEF) remains controversial. Herein, we conducted a network meta-analysis comparing coronary artery bypass graft (CABG), percutaneous coronary intervention (PCI), and optimal medical therapy (OMT) in patients with CAD and low LVEF.

Methods: MEDLINE and EMBASE were searched through March, 2021 to identify randomized controlled trials (RCTs) and propensity-score matched (PSM) studies comparing CABG, PCI, and OMT. We extracted hazard ratios (HRs) of the outcomes.

Results: A total of three RCTs and 10 PSM trials were identified, yielding a total of 18,855 patients with CAD with low EF who were treated with CABG (n = 9241), PCI (n = 8771), or OMT (n = 1003). All-cause mortality was significantly lower in patients with CABG compared with those with PCI or OMT (HR [95% confidence interval (CI)] = 0.72 [0.62-0.82], p < .001, HR [95% CI] = 0.65 [0.51-0.82], p = .004, respectively), while no difference was observed between PCI and OMT. The rates of MI were significantly lower in patients treated with CABG compared to those treated with PCI or OMT. However, the subgroup analysis by limiting the PCI group to patients who received drug-eluting stent (DES) showed similar all-cause mortality between CABG and PCI, while both CABG and PCI were associated with lower all-cause mortality compared with OMT.

Concluion: The present study demonstrated that CABG was the appropriate treatment strategy in patients with CAD and low LVEF. Further long-term trials were warranted to investigate outcomes of PCI with DES compared with CABG.
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http://dx.doi.org/10.1111/jocs.15850DOI Listing
October 2021
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