Publications by authors named "Phillip Freeman"

28 Publications

  • Page 1 of 1

Emergency department cardiovascular disease encounters and associated mortality in patients with cancer: A study of 20.6 million records from the USA.

Int J Cardiol 2022 Sep 22;363:210-217. Epub 2022 Jun 22.

Keele Cardiovascular Research Group, Centre for Prognosis Research, Keele University, UK; Department of Cardiology, Thomas Jefferson University Philadelphia, PA, USA; Institute of Population Health, University of Manchester, UK. Electronic address:

Background: there is limited data on Emergency department (ED) cardiovascular disease (CVD) presentations and outcomes amongst cancer patients.

Objectives: The present study aimed to describe the clinical characteristics, prevalence, and clinical outcomes of the most common cardiovascular ED admissions in patients with cancer.

Methods: All ED encounters with a primary CVD diagnosis from the US Nationwide Emergency Department Sample between January 2016 to December 2018 were stratified by cancer type as well as metastatic status. Multivariable logistic regression was performed to determine the adjusted odds ratios of in-hospital mortality in different groups.

Results: From a total of 20,737,247 ED encounters with a primary CVD diagnosis, cancer was present in 3.4%. In patients with cancer the most common CVDs were DVT/PE (20%), hypertensive heart or kidney disease (14.7%), and AF/flutter (11.2%). The distribution of CVDs varied by cancer type, with AF/flutter most common in patients with lung cancer, AMI most common in patients with prostate cancer, heart failure most common in those with haematological malignancies, and patients with colorectal cancer having the greatest frequency of DVT/PE. Cancer status was independently associated with significantly higher risk of mortality in almost all CVD categories, consistent across all the cancer types, amongst which lung cancer patients had the highest risk of mortality across all CVD categories, except intracranial haemorrhage and hypertensive crisis.

Conclusions: Cardiovascular presentations to the ED varied by cancer subtype. Across all cancer subtypes, patients presenting with cardiovascular presentations carried a significantly increased risk of mortality compared to patients with no cancer.
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http://dx.doi.org/10.1016/j.ijcard.2022.06.053DOI Listing
September 2022

Rationale and design of A study of patients with symptomatic moderate aortic valve stenosis and preserved left ventricular ejection fraction.

Int J Cardiol Heart Vasc 2022 Aug 27;41:101063. Epub 2022 May 27.

Weatherhead PET Center, Division of Cardiology, Department of Medicine, McGovern Medical School at UTHealth and Memorial Hermann Hospital, Houston, TX, USA.

Background: Moderate aortic valve stenosis occurs twice as often as severe aortic stenosis (AS) and carries a similarly poor prognosis. Current European and American guidelines offer limited insight into moderate AS (MAS) patients with unexplained symptoms. Measuring valve physiology at rest while most patients experience symptoms during exertion might represent a conceptual limitation in the current grading of AS severity. The stress aortic valve index (SAVI) may delineate hemodynamically significant AS among patients with MAS.

Objectives: To investigate the diagnostic value of SAVI in symptomatic MAS patients with normal left ventricular ejection fraction (LVEF ≥ 50%): aortic valve area (AVA) > 1 cm plus either mean valve gradient (MG) 15-39 mmHg or maximal aortic valve velocity (AOV max) 2.5-3.9 m/s. Short-term objectives include associations with symptom burden, functional capacity, and cardiac biomarkers. Long-term objectives include clinical outcomes.

Methods And Results: Multicenter, non-blinded, observational cohort. AS severity will be graded invasively (aortic valve pressure measurements with dobutamine stress testing for SAVI) and non-invasively (echocardiography during dobutamine and exercise stress). Computed tomography (CT) of the aortic valve will be scored for calcium, and hemodynamics simulated using computational fluid dynamics. Cardiac biomarkers and functional parameters will be serially monitored. The primary objective is to see how SAVI and conventional measures (MG, AVA and Vmax) correlate with clinical parameters (quality of life survey, 6-minute walk test [6MWT], and biomarkers).

Conclusions: The SAVI-AoS study will extensively evaluate patients with unexplained, symptomatic MAS to determine any added value of SAVI versus traditional, resting valve parameters.
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http://dx.doi.org/10.1016/j.ijcha.2022.101063DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9157233PMC
August 2022

Five-Year Outcomes After Coronary Computed Tomography Angiography (From 110,599 Patients in a Danish Nationwide Register-Based Follow-Up Study).

Am J Cardiol 2022 08 21;176:1-7. Epub 2022 May 21.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

The long-term cardiovascular risk for patients examined with coronary computed tomography angiography (CCTA) to rule out coronary heart disease compared with population controls remains unexplored. A nationwide register-based study including first-time CCTA-examined patients between 2007 and 2017 in Denmark alive 180 days post-CCTA was conducted. We evaluated 5-year outcomes of myocardial infarction (MI) or revascularization and all-cause mortality in 3 distinct CCTA-groups: (1) no post-CCTA preventive pharmacotherapy use (cholesterol-lowering drugs, antiplatelets, or anticoagulants); (2) post-CCTA preventive pharmacotherapy use; and (3) revascularization or MI within 180 days post-CCTA. For each patient group, population controls were matched on age, gender, and calendar year. Absolute risks standardized to the age, gender, selected co-morbidity, and anti-anginal pharmacotherapy distributions of the specific CCTA-examined patients and respective controls were obtained from multivariable Cox regression. Of 110,599 CCTA-examined patients, (1) 48,231 patients were not prescribed preventive pharmacotherapy 180 days post-CCTA; (2) 42,798 patients were prescribed preventive pharmacotherapy within 180 days post-CCTA; and (3) 19,570 patients were diagnosed with MI or revascularized within 180 days post-CCTA. For patient groups 1 to 3 versus respective controls, 5-year MI or revascularization risks were <0.1% versus 2.0%, <0.1% versus 3.8%, and 19.0% versus 2.5%, all p<0.001. Five-year all-cause mortality were 2.8% versus 4.2%, 5.5% versus 8.8%, and 6.7% versus 8.5%, all p <0.001. In conclusion, the 5-year MI or revascularization risk can be considered very low for CCTA-examined patients without ischemic events within 180 days post-CCTA. Conversely, CCTA-examined patients with MI or revascularization events within 180 days post-CCTA have significantly elevated 5-year MI or revascularization risk.
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http://dx.doi.org/10.1016/j.amjcard.2022.04.035DOI Listing
August 2022

Temporal trends in disease-specific causes of cardiovascular mortality amongst patients with cancer in the USA between 1999 to 2019.

Eur Heart J Qual Care Clin Outcomes 2022 Apr 18. Epub 2022 Apr 18.

Keele Cardiovascular Research Group, Keele University, Keele, UK.

Aims: We report disease-specific cardiovascular causes of mortality amongst cancer patients in the USA between 1999 to 2019, considering temporal trends by age, sex, and cancer site.

Methods And Results: We used the Multiple Cause of Death database, accessed through the CDC WONDER (Centres for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research) resource. We included 629,308 decedents with cardiovascular disease (CVD) recorded as the primary cause of death and active malignancy listed as a contributing cause of death. We created disease-specific CVD categories and grouped cancers by site. We calculated the proportion of CVD deaths attributed to each disease category stratified by sex, age, and cancer site. We also examined disease-specific temporal trends by cancer site. Ischaemic heart disease (IHD) was the most common cardiovascular cause of death across all cancer types (55.6%), being more common in men (59.8%), older ages, and in those with lung (67.8%) and prostate (58.3%) cancers. Cerebrovascular disease (12.9%) and hypertensive diseases (7.6%) were other common causes of death. The proportion of deaths due to heart failure was greatest in haematological (7.7%) and breast (6.3%) cancers. There was a decreasing temporal trend in the proportion of cardiovascular deaths attributed to IHD across all cancer types. The proportion of deaths due to hypertensive diseases showed the greatest percentage increase, with largest change in breast cancer patients (+191.1%).

Conclusions: We demonstrate differential cardiovascular mortality risk by cancer site and demographics, providing insight into the evolving healthcare needs of this growing high cardiovascular risk population.
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http://dx.doi.org/10.1093/ehjqcco/qcac016DOI Listing
April 2022

Impact of diabetes on clinical outcomes after revascularization with the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent and the sirolimus-eluting Orsiro stent.

Catheter Cardiovasc Interv 2022 06 6;99(7):1965-1975. Epub 2022 Apr 6.

Department of Cardiology, Odense University Hospital, Odense, Denmark.

Objectives: To compare the efficacy and safety of the dual therapy CD34 antibody-covered sirolimus-eluting Combo stent (DTS) and the sirolimus-eluting Orsiro stent (SES) in patients with and without diabetes mellitus (DM) included in the Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) X study.

Background: The incidence of target lesion failure (TLF) after treatment with modern drug-eluting stents has been reported to be significantly higher in patients with DM when compared to patients without DM. Thus, whether the results from the SORT OUT X study apply to patients with and without DM remains unknown.

Methods: In total 3146 patients were randomized to stent implantation with DTS (n = 1578; DM: n = 279) or SES (n = 1568; DM: n = 271). The primary end point, TLF, was a composite of cardiac death, target-lesion myocardial infarction (MI), or target lesion revascularization (TLR) within 1 year.

Results: At 1 year, the rate of TLF was increased in the DTS group compared to the SES group, both among patients with DM (9.3% vs. 4.8%; risk difference: 4.5%; incidence rate ratio: 1.99, 95% confidence interval [CI]: 1.02-3.90) and without DM (5.7% vs. 3.5%; incidence rate ratio: 1.67, 95% CI: 1.15-2.42). The differences were mainly explained by higher rates of TLR.

Conclusion: Compared to the SES, the DTS was associated with an increased risk of TLF at 12 months in patients with and without DM. The differences were mainly explained by higher rates of TLR, whereas rates of cardiac death and target lesion MI did not differ significantly between the two stent groups in patients with or without DM.
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http://dx.doi.org/10.1002/ccd.30175DOI Listing
June 2022

Risk for Myocardial Infarction Following 5-Fluorouracil Treatment in Patients With Gastrointestinal Cancer: A Nationwide Registry-Based Study.

JACC CardioOncol 2021 Dec 21;3(5):725-733. Epub 2021 Dec 21.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Background: Myocardial infarction is a cardiac adverse event associated with 5-fluorouracil (5-FU). There are limited data on the incidence, risk, and prognosis of 5-FU-associated myocardial infarction.

Objectives: The aim of this study was to examine the risk for myocardial infarction in patients with gastrointestinal (GI) cancer treated with 5-FU compared with age- and sex-matched population control subjects without cancer (1:2 ratio).

Methods: Patients with GI cancer treated with 5-FU between 2004 and 2016 were identified within the Danish National Patient Registry. Prevalent ischemic heart disease in both groups was excluded. Cumulative incidences were calculated, and multivariable regression and competing risk analyses were performed.

Results: A total of 30,870 patients were included in the final analysis, of whom 10,290 had GI cancer and were treated with 5-FU and 20,580 were population control subjects without cancer. Differences in comorbid conditions and select antianginal medications were nonsignificant ( > 0.05 for all). The 6-month cumulative incidence of myocardial infarction was significantly higher for 5-FU patients at 0.7% (95% CI: 0.5%-0.9%) versus 0.3% (95% CI: 0.3%-0.4%) in population control subjects, with a competing risk for death of 12.1% versus 0.6%. The 1-year cumulative incidence of myocardial infarction for 5-FU patients was 0.9% (95% CI: 0.7%-1.0%) versus 0.6% (95% CI: 0.5%-0.7%) among population control subjects, with a competing risk for death of 26.5% versus 1.4%. When accounting for competing risks, the corresponding subdistribution hazard ratios suggested an increased risk for myocardial infarction in 5-FU patients, compared with control subjects, at both 6 months (hazard ratio: 2.10; 95% CI: 1.50-2.95;  < 0.001) and 12 months (hazard ratio: 1.39; 95% CI: 1.05-1.84;  = 0.022).

Conclusions: Despite a statistically significantly higher 6- and 12-month risk for myocardial infarction among 5-FU patients compared with population control subjects, the absolute risk for myocardial infarction was low, and the clinical significance of these differences appears to be limited in the context of the significant competing risk for death in this population.
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http://dx.doi.org/10.1016/j.jaccao.2021.11.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702810PMC
December 2021

Polymer-free biolimus-coated stents versus ultrathin-strut biodegradable polymer sirolimus-eluting stents: two-year outcomes of the randomised SORT OUT IX trial.

EuroIntervention 2022 Jun 3;18(2):e124-e131. Epub 2022 Jun 3.

Department of Cardiology, Aarhus University Hospital, Skejby Hospital, Aarhus, Denmark.

Background: For patients with high bleeding risk, the BioFreedom stent is safer and more effective than a bare metal stent. However, at the one-year follow-up of the SORT OUT IX trial, the BioFreedom stent did not meet the criteria for non-inferiority for target lesion failure (TLF) when compared with the Orsiro stent and had a higher incidence of target lesion revascularisation (TLR).

Aims: The aim of the study was to compare the two-year outcomes following coronary implantation of the BioFreedom or the Orsiro stents in all-comer patients.

Methods: The Scandinavian Organization for Randomized Trials with Clinical Outcome (SORT OUT) IX trial is a prospective, multicentre, randomised clinical trial comparing the BioFreedom and the Orsiro stents. The primary endpoint, TLF, was a composite of cardiac death, myocardial infarction (MI; not related to other lesions) and TLR.

Results: A total of 1,572 patients were randomised to treatment with the BioFreedom stent and 1,579 patients with the Orsiro stent. At two-year follow-up, TLF was 7.8% in the BioFreedom and 6.3% in the Orsiro stent groups (rate ratio [RR] 1.23, 95% confidence interval [CI]: 0.94-1.61). Risks of cardiac death, MI and definite stent thrombosis did not differ significantly between the groups, whereas more patients in the BioFreedom group had TLR (5.1% vs 2.6%; RR 1.98, 95% CI: 1.26-2.89) attributable to a higher risk of TLR within the first year (3.5% vs 1.3%; RR 2.77, 95% CI: 1.66-4.62).

Conclusions: At two years, there were no significant differences between the BioFreedom and Orsiro stents for TLF. TLR was significantly higher with the BioFreedom stent due to higher risk of TLR within the first year.
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http://dx.doi.org/10.4244/EIJ-D-21-00874DOI Listing
June 2022

Mortality and ventricular arrhythmia after acute myocarditis: a nationwide registry-based follow-up study.

Open Heart 2021 10;8(2)

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Objective: Incidence and severity of acute myocarditis vary significantly in previous reports and there is a lack of epidemiological studies on the short-term risks of mortality, heart failure and ventricular arrhythmias in patients with acute myocarditis. Therefore, study aims were to examine 90-day risks of mortality, heart failure (HF) and ventricular arrhythmias in patients with acute myocarditis in comparison to age-matched and sex-matched background population controls.

Methods: In this nationwide register-based follow-up study of patients hospitalised with myocarditis between 2002 and 2018 in Denmark, 90-day risks of all-cause mortality, HF, ventricular arrhythmias (ventricular tachycardia, ventricular fibrillation (VF)), cardiac arrest and implantable cardioverter-defibrillator (ICD) implantation were compared with age-matched and sex-matched controls from the background population (1:5 matching). Absolute risks standardised to the age, sex and comorbidity distribution of the entire study population were derived from multivariable Cox regression.

Results: A total of 2523 patients hospitalised with myocarditis were included. Median age was 48 years (Q1-Q3: 30-69) and 67.7% were men. Comorbidity burden was more pronounced among patients with myocarditis relative to controls. Standardised 90-day all-cause mortality risk was 4.9% for patients with acute myocarditis versus 0.3% for controls (p<0.001). Ninety-day standardised risks for other endpoints were 7.5% versus 0.1% for HF, 1.9% versus <0.1% for VF/VF/arrest risk and 1.6% versus <0.1% for ICD implantation (all p<0.001).

Conclusions: In this large nationwide register-based follow-up study, patients hospitalised with myocarditis had significantly higher 90-day risks of all-cause mortality, HF, ventricular arrhythmias, cardiac arrest and ICD implantation compared with background population controls.
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http://dx.doi.org/10.1136/openhrt-2021-001806DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8532546PMC
October 2021

Mechanical circulatory support for refractory out-of-hospital cardiac arrest: a Danish nationwide multicenter study.

Crit Care 2021 05 22;25(1):174. Epub 2021 May 22.

Department of Cardiology, Aarhus University Hospital, Palle Juul-Jensens Boulevard 99, 8200, Aarhus N, Denmark.

Background: Mechanical circulatory support (MCS) with either extracorporeal membrane oxygenation or Impella has shown potential as a salvage therapy for patients with refractory out-of-hospital cardiac arrest (OHCA). The objective of this study was to describe the gradual implementation, survival and adherence to the national consensus with respect to use of MCS for OHCA in Denmark, and to identify factors associated with outcome.

Methods: This retrospective, observational cohort study included patients receiving MCS for OHCA at all tertiary cardiac arrest centers (n = 4) in Denmark between July 2011 and December 2020. Logistic regression and Kaplan-Meier survival analysis were used to determine association with outcome. Outcome was presented as survival to hospital discharge with good neurological outcome, 30-day survival and predictors of 30-day mortality.

Results: A total of 259 patients were included in the study. Thirty-day survival was 26%. Sixty-five (25%) survived to hospital discharge and a good neurological outcome (Glasgow-Pittsburgh Cerebral Performance Categories 1-2) was observed in 94% of these patients. Strict adherence to the national consensus showed a 30-day survival rate of 30% compared with 22% in patients violating one or more criteria. Adding criteria to the national consensus such as signs of life during cardiopulmonary resuscitation (CPR), pre-hospital low-flow < 100 min, pH > 6.8 and lactate < 15 mmol/L increased the survival rate to 48%, but would exclude 58% of the survivors from the current cohort. Logistic regression identified asystole (RR 1.36, 95% CI 1.18-1.57), pulseless electrical activity (RR 1.20, 95% CI 1.03-1.41), initial pH < 6.8 (RR 1.28, 95% CI 1.12-1.46) and lactate levels > 15 mmol/L (RR 1.16, 95% CI 1.16-1.53) as factors associated with increased risk of 30-day mortality. Patients presenting signs of life during CPR had reduced risk of 30-day mortality (RR 0.63, 95% CI 0.52-0.76).

Conclusions: A high survival rate with a good neurological outcome was observed in this Danish population of patients treated with MCS for OHCA. Stringent patient selection for MCS may produce higher survival rates but potentially withholds life-saving treatment in a significant proportion of survivors.
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http://dx.doi.org/10.1186/s13054-021-03606-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8141159PMC
May 2021

Randomized Clinical Comparison of the Dual-Therapy CD34 Antibody-Covered Sirolimus-Eluting Combo Stent With the Sirolimus-Eluting Orsiro Stent in Patients Treated With Percutaneous Coronary Intervention: The SORT OUT X Trial.

Circulation 2021 06 7;143(22):2155-2165. Epub 2021 Apr 7.

Department of Cardiology, Odense University Hospital, Denmark (K.V., J.E., O.A., A.A., A.J., H.S.H., L.O.J.).

Background: Target lesion failure remains an issue with contemporary drug-eluting stents. Thus, the dual-therapy sirolimus-eluting and CD34+ antibody-coated Combo stent (DTS) was designed to further improve early healing. This study aimed to investigate whether the DTS is noninferior to the sirolimus-eluting Orsiro stent (SES) in an all-comers patient population.

Methods: The SORT OUT X (Combo Stent Versus Orsiro Stent) trial, was a large-scale, randomized, multicenter, single-blind, 2-arm, noninferiority trial with registry-based follow-up. The primary end point target lesion failure was a composite of cardiac death, myocardial infarction, or target lesion revascularization within 12 months, analyzed using intention-to-treat. The trial was powered for assessing target lesion failure noninferiority of the DTS compared with the SES with a predetermined noninferiority margin of 0.021.

Results: A total of 3146 patients were randomized to treatment with the DTS (1578 patients; 2008 lesions) or SES (1568 patients; 1982 lesions). At 12 months, intention-to-treat analysis showed that 100 patients (6.3%) assigned the DTS and 58 patients (3.7%) assigned the SES met the primary end point (absolute risk difference, 2.6% [upper limit of 1-sided 95% CI, 4.1%]; (noninferiority)=0.76). The SES was superior to the DTS (incidence rate ratios for target lesion failure, 1.74 [95% CI, 1.26-2.41]; =0.00086). The difference was explained mainly by a higher incidence of target lesion revascularization in the DTS group compared with the SES group (53 [3.4%] vs. 24 [1.5%]; incidence rate ratio, 2.22 [95% CI, 1.37-3.61]; =0.0012).

Conclusions: The DTS did not confirm noninferiority to the SES for target lesion failure at 12 months in an all-comer population. The SES was superior to the DTS mainly because the DTS was associated with an increased risk of target lesion revascularization. However, rates of death, cardiac death, and myocardial infarction at 12 months did not differ significantly between the 2 stent groups. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03216733.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.120.052766DOI Listing
June 2021

Long-term impact of baseline anaemia on clinical outcomes following percutaneous coronary intervention in stable angina.

Open Heart 2020 10;7(2)

Department of Cardiology and Clinical Medicine, Aalborg University Hospital, Aalborg, Nordjylland, Denmark.

Background: In patients with stable angina (SA), the clinical benefits of percutaneous coronary intervention (PCI) reside almost exclusively within the realm of symptomatic improvement rather than improvement in hard clinical endpoints. The benefits of PCI should always be balanced against its potential short-term and long-term risks. Common among these risks is the presence of anaemia and its interaction with poor clinical outcomes and increased morbidity; this study aims to elucidate the impact of anaemia on long-term clinical outcomes of this patient group.

Methods: From Danish national registries, we identified patients with SA treated with PCI who had a haemoglobin measurement maximum of 90 days prior to PCI procedure. Anaemia was defined as haemoglobin <130 and <120 g/L in men and women, respectively. Follow-up was up to 3 years after PCI, and Cox regression was used to estimate HRs with 95% CIs of hospitalisation due to bleeding, acute coronary syndrome (ACS) and all-cause mortality in patients with anaemia compared with patients without anaemia.

Results: Of 2837 included patients, 14.6% had anaemia prior to PCI. During follow-up, 93 patients (3.3%) had a bleeding episode, which was higher in patients with anaemia (5.8%) compared with patients without anaemia (2.8%). A total of 213 patients (7.5%) developed ACS, which was higher in patients with anaemia (10.6%) compared with patients without anaemia (7.0%). Furthermore, 185 patients (6.5%) died, with a mortality rate of 18.1% in patients with anaemia compared with 4.5% in patients without anaemia. In multivariable analyses, anaemia was associated with a significantly increased risk of bleeding (HR 1.69; 95% CI 1.04 to 2.73; P 0.033), ACS (HR 1.47; 95% CI 1.04 to 2.10; P 0.031) and all-cause mortality (HR 2.41; 95% CI 1.73 to 3.30; P <0.001).

Conclusion: Anaemia in patients with SA was significantly associated with bleeding, ACS and all-cause mortality following PCI.
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http://dx.doi.org/10.1136/openhrt-2020-001319DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7534726PMC
October 2020

Characterisation of patients with and without cardiac magnetic resonance imaging abnormalities presenting with myocardial infarction with non-obstructive coronary arteries (MINOCA).

Acta Cardiol 2021 Sep 29;76(7):760-768. Epub 2020 Jun 29.

Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.

Objective: The objective of the current study is to determine the characteristics of myocardial infarction with non-obstructive coronary arteries (MINOCA) patients with and without cardiac magnetic resonance (CMR) abnormalities.

Methods: We evaluated patients admitted with a presentation of acute myocardial infarction (MI) with no coronary obstruction on invasive angiography in our institution between 2012 and 2017. Patients with prior cardiac disease, myocarditis, Takotsubo cardiomyopathy and type 2 myocardial infarction were excluded. Myocardial fibrosis was determined by late gadolinium enhancement (LGE). Patients were divided into two groups based on the presence or absence of CMR abnormalities (LGE or oedema). Major adverse cardiovascular events (MACE) were defined as non-fatal MI, all-cause mortality, ventricular arrythmias or heart failure hospitalisation at follow-up.

Results: Thirty-four patients fulfilling the inclusion criteria were identified. Myocardial changes with CMR were observed in 20 (59%) patients with signs of subendocardial infarct by LGE in 13 (38%) patients, transmural infarct by LGE in 6 (18%) patients and one patient had myocardial oedema. ECG and echocardiographic features were similar between patients with and without CMR abnormalities. Troponin T was significantly higher among patients with CMR abnormalities. The median duration of follow-up was 702 (IQR 456-1394) days. Two patients had MACE (both heart failure). One of them had LGE changes.

Conclusions: A significant number of patients with MINOCA have ischaemic LGE changes or myocardial wall oedema. The patients with CMR abnormalities have similar ECG and echocardiographic features except higher biomarker, highlighting the role of CMR in patients with MINOCA.
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http://dx.doi.org/10.1080/00015385.2020.1785134DOI Listing
September 2021

Monomorphic ventricular tachycardia as the primary presentation of an anterior STEMI.

Clin Case Rep 2019 Sep 26;7(9):1680-1684. Epub 2019 Jul 26.

Department of Cardiology Aalborg University Hospital Aalborg Denmark.

Traditionally sustained monomorphic ventricular tachycardia (SMVT) is associated with areas of myocardial scar such as that of chronic coronary artery disease. We present a case of SMVT in the initial setting of an acute myocardial infarction in a previously healthy individual suggesting that acute ischemia can give rise to SMVT.
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http://dx.doi.org/10.1002/ccr3.2324DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6745393PMC
September 2019

Combinations of bleeding and ischemic risk and their association with clinical outcomes in acute coronary syndrome.

Int J Cardiol 2019 09 21;290:7-14. Epub 2019 May 21.

Keele Cardiovascular Research Group, Institutes of Applied Clinical Science and Primary Care and Health Sciences, Keele University, Stoke-on-Trent, UK; Department of Cardiology, Royal Stoke Hospital, University Hospital North Midlands, Stoke-on-Trent, UK. Electronic address:

Background: Clinical predictors of future ischemic events in patients with acute coronary syndrome (ACS) are also risk factors for bleeding, with patients often at high-risk of both outcomes. We aimed to define the clinical outcomes and provision of guideline-recommended care in ACS management for different combinations of ischemic and bleeding risk defined using a combined GRACE and CRUSADE score.

Methods: A retrospective observational analysis of a national ACS database was performed for patients with ACS admitted to three tertiary centres from January 2010 to March 2016. Patients were stratified into 9 groups based on possible CRUSADE-GRACE risk combinations. Multiple logistic regression was used to estimate adjusted odds ratios (ORs [95% CI]) for outcomes (in-hospital net adverse cardiac events (NACE), in-hospital all-cause mortality, 30-day mortality and treatment strategy).

Results: A total of 17,701 patients were included in the analysis. We observed a graded risk of mortality and adverse events in the high-risk GRACE strata (Groups 3, 6 and 9). Almost a third of patients with ACS were at a 'dual high-risk' (Group 9, 32%) and were independently associated with higher in-hospital NACE (composite of cardiac mortality, all-cause bleeding and re-infarction): aOR 6.33 [3.55, 11.29], all-cause mortality: aOR 14.17 [5.27, 38.1], all-cause bleeding: aOR 4.82 [1.96, 11.86], and 30-day mortality: aOR 10.79 [5.33, 21.81]. This group was also the least likely to be offered coronary angiography (aOR 0.24 [0.20, 0.29]) and dual anti-platelet therapy (aOR 0.26 [0.20, 0.34]).

Conclusions: One in five patients presenting with an ACS are high ischemic and high bleeding risk, and these patients are more likely to experience poor clinical outcomes and reduced odds of receiving guideline-recommended therapy.
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http://dx.doi.org/10.1016/j.ijcard.2019.05.035DOI Listing
September 2019

The effect of schizophrenia on major adverse cardiac events, length of hospital stay, and prevalence of somatic comorbidities following acute coronary syndrome.

Eur Heart J Qual Care Clin Outcomes 2019 04;5(2):121-126

Department of Cardiology, Aalborg University Hospital, Hobrovej 18, Aalborg, Denmark.

Aims: We aimed to investigate major adverse cardiac events (MACE: defined as all-cause mortality, re-infarction, and stroke), length of hospital stays (LOS), and comorbidities following acute coronary syndrome (ACS) in a population with schizophrenia.

Methods And Results: This Danish register study included patients diagnosed with ACS in the period between 1995 and 2013 with a preceding diagnosis of schizophrenia (n = 726). Each patient was matched to a psychiatric healthy control 1:2 on sex, age, year of ACS diagnosis, and number of comorbidities (total n = 2178). After performing Cox regression and Kaplan-Meier analyses, we found that patients with schizophrenia had an increased risk of MACE [hazard ratio (HR) 1.62, 95% confidence interval (CI) 1.45-1.81], all-cause mortality (HR 2.54, 95% CI 2.22-2.90), and stroke (HR 1.51, 95% CI 1.15-1.99). No differences were found in the re-infarction rates and LOS between the populations. Patients with schizophrenia had higher prevalence's diabetes, anaemia, heart failure, cardiomyopathy, chronic obstructive lung disease, and stroke. Nonetheless, we found lower prevalence's of hypertension and hyperlipidaemia.

Conclusion: Schizophrenia is associated with an increased risk of MACE despite a lower prevalence of some diagnosed traditional cardiac risk factors which may indicate underdiagnosing of these. Awareness of treatment bias may improve this increased risk.
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http://dx.doi.org/10.1093/ehjqcco/qcy055DOI Listing
April 2019

Chronic total coronary occlusion: treatment results.

Scand Cardiovasc J 2017 Aug 20;51(4):197-201. Epub 2017 Apr 20.

a Department of Cardiology , Aalborg University Hospital , Aalborg , Denmark.

Objectives: To describe the clinical and procedural coronary chronic total occlusion (CTO) treatment results in a Nordic PCI centre during the implementation of a CTO treatment program.

Design: In a retrospective registry study, we assessed; (1) indication for the procedure, (2) Canadian Cardiovascular Society angina pectoris score (CCS)/New York Heart Association (NYHA) heart failure score, (3) lesion complexity and (4) adverse events during hospital stay and three months following the index procedure.

Results: The study cohort included 503 patients (594 lesions). From 2010 to 2013 96% of procedures were performed with antegrade wire-escalation technique and 4% performed using retrograde techniques, from 2013-2016 the corresponding numbers were 83% and 17.0%. The procedural success rate was 69%, increasing from 64% before to 72% (p = .06) after routinely using the retrograde approach. No individual patient characteristic, lesion variable or score was strongly associated with procedural success or failure. There were 4% serious procedure related complications. In patients with PCI of a CTO lesion only, 87% were in CCS or NYHA functional class ≥2 before the index procedure vs. 22% at follow-up.

Conclusions: Routine use of retrograde techniques tended to increase the procedural success rate. Clinical results after three months were acceptable, but the complication rate was higher than for non-CTO PCI. Individual patient and lesion characteristics had a low predictability for procedural success. Therefore, clinical symptoms, objective signs of myocardial ischemia and procedural risk should be focus points in coronary chronic total occlusion treatment strategies.
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http://dx.doi.org/10.1080/14017431.2017.1319575DOI Listing
August 2017

Statins for secondary prevention: clinical use in patients with acute coronary syndrome in Wales.

Future Cardiol 2017 03 10;13(2):137-141. Epub 2017 Feb 10.

Institute of Population Medicine, Cardiff University, Wales, UK.

Aim: Statins have a proven role for the secondary prevention of cardiovascular disease. Despite this, typical patient use in real life is variable. Our aim was to investigate the typical clinical use, including adherence, for statins in a sample population in South Wales (UK).

Methods: We identified 2248 patients admitted to hospitals in South Wales with acute coronary syndrome using a retrospective 3-year-long longitudinal study. We performed data linkage using the Secure Anonymized Information Linkage databank.

Results & Conclusion: In total, 1806 (80.3%) of patients were initiated on statins at discharge, with simvastatin being most common. Only 38% of patients were on high-intensity dosage. There was minimal change in cholesterol levels, with discontinuation rates of 53.7 and 84.3% at 1- and 3-year follow-up, respectively.
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http://dx.doi.org/10.2217/fca-2016-0060DOI Listing
March 2017

Increased morbidity, mortality and length of in-hospital stay for patients with acute coronary syndrome with pre-morbid psychiatric diagnoses.

Int J Cardiol 2017 Jun 9;236:5-8. Epub 2017 Jan 9.

Institute of Population Medicine, Cardiff University, Wales, UK; Department of Cardiology, Aalborg University Hospital, Denmark.

Background: Psychiatric and cardiac comorbidities form the top two budget categories for health systems in high-income countries with evidence that psychiatric pre-morbidities lead to worse outcomes in patients with acute coronary syndrome (ACS). There are no studies examining this relationship in a national multicentre population level study in the UK, and no studies examining their impact on length of in-hospital stay (LoS) in ACS. Recognizing at-risk populations and reducing LoS in ACS is an essential part of improving patient care and cost-effectiveness.

Methods: We investigated the impact of psychiatric diagnoses on morbidity, all-cause mortality and LoS amongst 57,668 ACS patients between Jan-2004 and Dec-2014 using the Secure-Anonymized-Information-Linkage (SAIL) databank. Demographics, admissions, cardiac and psychiatric comorbidities were identified using coded data.

Results: There were a total of 3857 out of 57,668 patients who had a pre-morbid psychiatric diagnosis. The mean LoS in patients without psychiatric comorbidities was 9.78days (95% CI: 9.66-9.91). This was higher (p<0.01) in the presence of any psychiatric diagnosis (14.72), dementia (20.87), schizophrenia (15.67), and mood disorders (13.41). Patients with psychiatric comorbidities had worse net adverse cardiac events (HR 1.18, 95% CI: 1.16-1.21) and mortality rates (HR 1.26, 95% CI: 1.23-1.30).

Conclusions: Our results demonstrate that psychiatric comorbidities have a significant and clinically important impact on morbidity, mortality and LoS in ACS patients in Wales, UK. Clinicians' awareness and active management of psychiatric conditions amongst ACS patients is needed to reduce poor outcomes and LoS and ultimately the risk for patients and financial burden for the health-service.
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http://dx.doi.org/10.1016/j.ijcard.2017.01.067DOI Listing
June 2017

Acute coronary syndrome on Friday the 13th: a case for re-organising services?

Med J Aust 2016 Dec;205(11):523-525

Cardiff University School of Medicine, Cardiff, Wales, United Kingdom.

Background: Friday the 13th is described as an "unlucky" day that brings misfortune. There are few studies on the question, and none on its effect in cardiovascular patients. The recently misreported "weekend effect" has led to changes in the junior doctor contract in England, providing greater staffing levels on weekends. Should we make similar provisions for Friday the 13th?

Methods: A retrospective analysis of a large database for patients admitted to hospitals in South Wales with an acute coronary syndrome (ACS) during 1999-2014. Mortality rates for 217 admission day number/name combinations and for Friday the 13th were compared in a Cox proportional hazards regression model.

Results: 56 062 ACS patients were identified. There were no significant differences in 13-year mortality between most admission dates (211 of 216) and Friday the 13th. However, a statistically significant reduction in mortality was identified for five dates: Thursday the 15th (HR, 0.77; 95% CI, 0.59-0.999), Wednesday the 18th (HR, 0.76; 95% CI, 0.58-0.99), Monday the 28th (HR, 0.76; 95% CI, 0.57-0.99), Monday the 30th (HR, 0.75; 95% CI, 0.57-0.99) and Tuesday the 31st (HR, 0.71; 95% CI, 0.51-0.99).

Conclusion: On most days, there was no difference in the 13-year mortality rate for patients admitted with their first ACS from that for "unlucky" Friday the 13th. However, patients admitted on five day/number combinations were 20-30% more likely to survive at 13 years. These findings could be explained by subgroup analysis inflation of the type I error, although supernatural causes merit further investigation. Our findings should be taken into account in future junior doctor contract negotiations, and may provide a case for reduced staffing levels on these lucky days.
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http://dx.doi.org/10.5694/mja16.00870DOI Listing
December 2016

Severe symptomatic aortic stenosis: medical therapy and transcatheter aortic valve implantation (TAVI)-a real-world retrospective cohort analysis of outcomes and cost-effectiveness using national data.

Open Heart 2016;3(1):e000414. Epub 2016 Jun 8.

Morriston Hospital, Swansea, UK; Swansea University, Swansea, UK.

Objectives: Determine the real-world difference between 2 groups of patients with severe aortic stenosis and similar baseline comorbidities: surgical turn down (STD) patients, who were managed medically prior to the availability of transcatheter aortic valve implantation (TAVI) following formal surgical outpatient assessment, and patients managed with a TAVI implant.

Design: Retrospective cohort study from real-world data.

Setting: Electronic patient letters were searched for patients with a diagnosis of severe aortic stenosis and a formal outpatient STD prior to the availability of TAVI (1999-2009). The second group comprised the first 90 cases of TAVI in South Wales (2009 onwards). 2 years prior to and 5 years following TAVI/STD were assessed. Patient data were pseudoanonymised, using the Secure Anonymized Information Linkage (SAIL) databank, and extracted from Office National Statistics (ONS), Patient-Episode Database for Wales (PEDW) and general practitioner databases.

Population: 90 patients who had undergone TAVI in South Wales, and 65 STD patients who were medically managed.

Main Outcome Measures: Survival, hospital admission frequency and length of stay, primary care visits, and cost-effectiveness.

Results: TAVI patients were significantly older (81.8 vs 79.2), more likely to be male (59.1% vs 49.3%), baseline comorbidities were balanced. Mortality in TAVI versus STD was 28% vs 70% at 1000 days follow-up. There were significantly more hospital admissions per year in the TAVI group prior to TAVI/STD (1.5 (IQR 1.0-2.4) vs 1.0 IQR (0.5-1.5)). Post TAVI/STD, the TAVI group had significantly lower hospital admissions (0.3 (IQR 0.0-1.0) vs 1.2 (IQR 0.7-3.0)) and lengths of stay (0.4 (IQR 0.0-13.8) vs 11.0 (IQR 2.5-28.5), p<0.05). The incremental cost-effectiveness ratio (ICER) for TAVI was £10 533 per quality-adjusted life year (QALY).

Conclusions: TAVI patients were more likely to survive and avoid hospital admissions compared with the medically managed STD group. The ICER for TAVI was £10 533 per QALY, making it a cost-effective procedure.
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http://dx.doi.org/10.1136/openhrt-2016-000414DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4908912PMC
June 2016

Chronic anemia and non-ST elevation acute coronary syndrome - double jeopardy.

Curr Med Res Opin 2016 09 26;32(9):1503-9. Epub 2016 Jul 26.

b University Hospital of Wales, Heath Park , Cardiff , UK ;

This review outlines the priorities from cardiology and gastroenterology perspectives, resolves some of the misconceptions, and uses the evidence available to suggest strategies for optimizing management of these patients. The dual presentation of acute active gastrointestinal (GI) blood loss together with an acute coronary syndrome (NSTEACS or STEMI) is outside the remit of this review but has been previously reviewed by our group. The review covers NSTEACS together with chronic or sub-acute anemia, anemia that cannot be accounted for by chronic kidney disease, heart failure, or inflammatory disorders. Identification of a potential GI etiology of anemia is important as it allows adjustment to both GI and CV investigations and treatments that can reduce the likelihood and impact of bleeding complications.
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http://dx.doi.org/10.1080/03007995.2016.1182902DOI Listing
September 2016

Temporomandibular Joint Septic Arthritis and Mandibular Osteomyelitis Arising From an Odontogenic Infection: A Case Report and Review of the Literature.

J Oral Maxillofac Surg 2016 Apr 6;74(4):754-63. Epub 2015 Nov 6.

Associate Professor, Department of Oral and Maxillofacial Surgery, University of Texas-Houston Health Science Center, Houston, TX.

Septic arthritis of the temporomandibular joint (TMJ) has been infrequently reported in the literature. Some investigators believe that this condition is under-reported because it is underdiagnosed. Misdiagnosis or late diagnosis of this condition can lead to serious morbidity, including fistula formation, intracranial abscess, fibrous or bony ankylosis, temporal bone or condylar osteomyelitis, growth alteration, and several others. This report describes a case of septic TMJ arthritis arising from direct spread of an odontogenic infection with subsequent development of mandibular osteomyelitis. The purpose of this case report is to 1) increase awareness of an underdiagnosed condition, 2) establish the seriousness of this infection, 3) for the first time report on a case of TMJ septic arthritis caused by Bacteroides infection, and 4) provide a review of the relevant literature.
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http://dx.doi.org/10.1016/j.joms.2015.11.003DOI Listing
April 2016

Changes in platelet function independent of pharmacotherapy following coronary intervention in non-ST-elevation myocardial infarction patients.

Atherosclerosis 2015 Nov 21;243(1):320-7. Epub 2015 Sep 21.

Cardiothoracic Directorate, University Hospital of Wales, UK.

Background: High on treatment platelet reactivity (HTPR) is common in patients receiving clopidogrel following an acute coronary syndrome (ACS); it's also associated with increased morbidity and mortality. More potent and predictable antiplatelet drugs have addressed this issue at the expense of increased bleeding. Identification of HTPR and the targeted use of more potent antiplatelet drugs has, so far, broadly failed. We investigate this approach in terms of the timing of platelet function testing and how this can impact on the ability of these bedside tests to predict HTPR around the time of coronary intervention.

Methods: High risk ACS patients treated with 5 days of clopidogrel had platelet function assessed using the multiple electrode aggregometry system (MEA) pre, post and 24 h following percutaneous coronary intervention (PCI). Simultaneous detailed analysis of platelet status was undertaken with quantification of platelet bound and soluble p-selectin and mass spectrometry quantification of the eicosanoid 12-HETE.

Results: As assessed by MEA 40.5% of patients had HTPR pre-PCI; mean aggregation units (AU) in response to ADP were 499.1 ± 46.3 pre-PCI, 407.6 ± 37.7 post-PCI and 269.1 ± 24.6 AU 24 h post-PCI (pre to post PCI p > 0.05, pre to 24 h post-PCI p = 0.0002). This highly significant drop in platelet reactivity was contrasted with on-going expression of platelet bound p-selectin, increased soluble p-selectin and rising 12-HETE concentrations.

Conclusions: This study outlines significant changes in ex-vivo platelet aggregation that occur within 24 h of PCI in high risk NSTEMI patients using bedside PFT. Whilst there were no changes in antiplatelet therapy during the study period its clear that timing is crucial when assessing high on treatment residual platelet activity.
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http://dx.doi.org/10.1016/j.atherosclerosis.2015.09.024DOI Listing
November 2015

Changes in Intraocular Pressure During Orbital Floor Fracture Repair.

Ophthalmic Plast Reconstr Surg 2015 Jul-Aug;31(4):303-5

*Department of Ophthalmology, Alkek Eye Center, Baylor College of Medicine; †Department of Oral and Maxillofacial Surgery, University of Texas Health Science Center, Houston, Texas; ‡Department of Ophthalmology, Casey Eye Institute, Oregon Health and Sciences University, Portland, Oregon; and §Department of Ophthalmology, Oculofacial Plastic and Orbital Surgery, Gavin Herbert Eye Institute, University of California, Irvine, California, U.S.A.

Purpose: To evaluate changes in intraocular pressure (IOP) during orbital floor fracture repair.

Methods: Retrospective chart review of patients undergoing isolated orbital floor fracture repair with implant placement at a level 1 trauma center and tertiary care center. Patients with combined zygomaticomaxillary or medial wall fracture repair, or other significant ocular injuries were excluded. IOP measurements using a handheld applanation tonometer were recorded immediately after induction of anesthesia, immediately after orbital floor implant placement, and on postoperative day 1.

Results: Nine patients who underwent isolated orbital floor fracture repair were examined. There was a statistically significant mean decrease of 4.66 mmHg (p < 0.05) in IOP from prior to surgical to immediately after implant placement. There was also a significant mean increase in IOP of 7.44 mmHg (p < 0.05) at postoperative day 1 compared with immediately after implant placement. There was no statistically significant difference in IOP between prior to surgical incision and postoperative day 1.

Conclusions: All patients who underwent orbital floor fracture repair in this study had a significant decrease in IOP during orbital floor fracture repair that returned to immediately preoperative levels by postoperative day 1. This initial decrease in IOP may be because of intraoperative manipulation of the globe.
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http://dx.doi.org/10.1097/IOP.0000000000000322DOI Listing
February 2016

Discharge after primary angioplasty at 24 h: feasible and safe or a step too far?

Cardiology 2013 12;125(3):176-9. Epub 2013 Jun 12.

Department of Cardiology, Royal United Hospital Bath, UK.

Current clinical practice regarding surveillance period and length of hospital stay after an ST elevation myocardial infarction is very variable among different countries and hospitals. In general, there has been a significant reduction in length of stay overall, which is mainly due to the increasing use of primary percutaneous coronary intervention. Length of stay after a ST elevation myocardial infaction, which is a rather common event, has a major impact on health care costs and patients' quality of life. We try to evaluate how far we could push the limits.
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http://dx.doi.org/10.1159/000351186DOI Listing
March 2014

Saphenous vein graft percutaneous coronary intervention via radial artery access: safe and effective with reduced hospital length of stay.

Am Heart J 2012 Oct;164(4):468-72

University Hospital of Wales, Heath Park, Cardiff, Wales, United Kingdom.

Background: Although percutaneous coronary intervention (PCI) via radial artery access confers many advantages over the femoral artery, PCI to saphenous vein grafts (SVG) is commonly performed via the femoral route. We compared outcomes in patients undergoing SVG PCI from the radial and femoral routes.

Methods: We performed a retrospective analysis of patients who underwent SVG PCI between January 2006 and December 2010 in 2 large interventional centers in the United Kingdom. All radial and femoral operators selected for this analysis performed high-volume (>200 PCIs per year) procedures via either vascular route.

Results: Of 305 patients (260 males) who underwent SVG PCI, 208 (68.2%) had the procedure completed from the femoral route and 97 (32.8%) radially. There was no difference between groups in fluoroscopy time (femoral vs radial 1095 vs 1125 seconds, P nonsgnificant), but radiation doses were greater (43.87 ± 2.83 Gy/cm(2) vs 56.92 ± 4.52 Gy/cm(2), P = .012) as was body mass index in the radial group (27.99 ± 0.33 vs 29.05 ± 0.42, P = .048). Three femoral access patients had vascular access complications, whereas the radial route group had none. There were no differences in no flow/slow flow (femoral 3.86% vs radial 2.54%, P nonsignificant). The mean length of hospital stay was significantly shorter in the radial access cohort (1.09 vs 2.09 days, P < .001). Three patients converted from radial to femoral artery, whereas one converted from femoral to radial after technical failure to complete the procedure.

Conclusion: Saphenous vein graft PCI can be safely and effectively performed via radial artery access with comparable fluoroscopy times but not radiation doses. Of clinical significance, use of the radial artery access was associated with decreased hospital stay and arterial complications. These data suggest that a routine radial approach for SVG PCI is feasible and could offer clinical and economic benefits.
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http://dx.doi.org/10.1016/j.ahj.2012.07.029DOI Listing
October 2012
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