Publications by authors named "Patrick A Calvert"

48 Publications

Impact of percutaneous patent foramen ovale closure on migraine headaches in patients with history of ischemic neurological events.

Postepy Kardiol Interwencyjnej 2020 Sep 2;16(3):315-320. Epub 2020 Oct 2.

Department of Cardiology, Royal Papworth Hospital, Cambridge, United Kingdom.

Introduction: Observational studies have shown that migraine has been associated with patent foramen ovale (PFO). Whilst studies investigating PFO closure for the treatment of migraine have been neutral, there is some evidence that symptoms of migraine may improve if the PFO was closed after ischemic stroke.

Aim: To establish whether closure of PFO in patients with stroke or transient ischemic attack (TIA) is associated with reduction in the severity of co-existent migraine headaches.

Material And Methods: Patients with ischemic stroke or TIA, PFO suitable for percutaneous closure and migraine, were given migraine severity questionnaires prior to PFO closure. These were followed up at 6 and 12 months after closure with the same questionnaire. The primary endpoint was change in migraine severity using the Migraine Severity Scale (MIGSEV). Migraine episode frequency, disability (using the MIDAS scale), and pain intensity were also assessed.

Results: Sixty-two patients were included in the analysis. MIGSEV scores reduced from 7 (7-8) at baseline to 4 (3.25-6) at 6-month follow-up, and 3 (0-4) at 12-month follow-up ( < 0.001). Other measures of migraine headache were also improved at both 6- and 12-month follow-up. Twenty-four (38%) patients were rendered migraine free at 12 months.

Conclusions: PFO closure for stroke or TIA prevention in patients with migraine was associated with a reduction in markers of migraine headache severity.
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http://dx.doi.org/10.5114/aic.2020.99267DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863799PMC
September 2020

Patent Foramen Ovale Closure: State of the Art.

Interv Cardiol 2020 Apr 24;15:e15. Epub 2020 Nov 24.

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people, it is a benign finding; however, in some people, the PFO can open widely to enable paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of the PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised control trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this article considers the evidence for PFO closure in cryptogenic stroke. The article also addresses other potential indications for closure, including systemic arterial embolisation, decompression sickness, platypnoea-orthodeoxia syndrome and migraine with aura. The article lays out the pre-procedural investigations and preparation for the procedure. Finally, the article gives an overview of the procedure itself, including discussion of closure devices.
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http://dx.doi.org/10.15420/icr.2019.27DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7726850PMC
April 2020

28 days later: a traumatic pacing indication and the role of cardiac imaging as the pathologist.

Eur Heart J Cardiovasc Imaging 2020 Nov 9. Epub 2020 Nov 9.

Royal Papworth Hospital, Cambridge Biomedical Campus, Cambridge CB2 0AY, UK.

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http://dx.doi.org/10.1093/ehjci/jeaa283DOI Listing
November 2020

Transcatheter treatment of postinfarct ventricular septal defects.

Heart 2020 Jun 28;106(12):878-884. Epub 2020 Feb 28.

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK

Postinfarct ventricular septal defects (VSDs) are a mechanical complication of acute myocardial infarction (AMI) with a very poor prognosis. They are estimated to occur in 0.2% of patients presenting with AMI, with 1-month survival of 6% without intervention. Guidelines recommend surgical repair, but recent advances in transcatheter technology, and bespoke device development, mean it is increasingly viable as a closure option. Surgical mortality is between 30% and 50% for all-comers, while in series of transcatheter closure, mortality was 32%. Transcatheter closure appears durable, with no evidence of late leaks and low long-term mortality in series with up to 5-year follow-up. Guidelines recommend early closure, which is likely to provide most benefit for patients regardless of the closure method. Multimodality cardiac imaging including echocardiography, CT and cardiac MRI can define size, shape, location of defects and their relationship to other cardiac structures, assisting with treatment decisions. Brief delay to allow stabilisation of the patient is appropriate, but untreated patients risk rapid deterioration. Mechanical circulatory support may be helpful, although the preferred modality is unclear. Transcatheter closure involves large bore venous access and the formation of an arteriovenous loop (under fluoroscopic and trans-oesophageal echocardiographic guidance) in order to facilitate deployment of the device in the defect and close the postinfarct VSD. Guidelines suggest transcatheter closure as an alternative to surgical repair in centres where appropriate expertise exists, but decisions for all patients with postinfarct VSD should be led by the multidisciplinary heart team.
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http://dx.doi.org/10.1136/heartjnl-2019-315751DOI Listing
June 2020

Coronary perforation complicating percutaneous coronary intervention in patients presenting with an acute coronary syndrome: An analysis of 1013 perforation cases from the British Cardiovascular Intervention Society database.

Int J Cardiol 2020 01 14;299:37-42. Epub 2019 Jun 14.

Keele Cardiovascular Research Group, Institute of Applied Clinical Sciences, University of Keele, Stoke-on-Trent, UK; Royal Stoke Hospital, UHNM, Stoke-on-Trent, UK.

Background: The evidence base for coronary perforation occurring during percutaneous coronary intervention in patients presenting with an acute coronary syndrome (ACS-PCI) is limited and the specific role of acute pharmacology in its clinical presentation unclear.

Methods And Results: Using the BCIS PCI database, data were analysed on all ACS-PCI procedures performed in England and Wales between 2007 and 2014. Multiple regressions were used to identify predictors of coronary perforation and its association with outcomes. Propensity score matching was used to evaluate the association between differing P2Y12 inhibitors or glycoprotein inhibitors (GPI) and CP. During 270,329 ACS-PCI procedures, 1013 coronary perforations were recorded (0.37%) with a stable annual incidence. In multiple regression analysis, covariates associated with increased frequency of coronary perforation included age, female gender, CTO intervention, number and length of stents used, and rotational atherectomy use, whilst differing P2Y12 inhibitors were not predictive. Using propensity score matching, use of a GPI was independently associated with tamponade (OR 1.50, [1.08-2.06], p = 0.014). The adjusted odds ratios for all clinical outcomes were adversely affected by coronary perforation.

Conclusions: Coronary perforation is an infrequent event during ACS-PCI but is closely associated with adverse clinical outcomes. GPI use was associated with higher rates of tamponade.
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http://dx.doi.org/10.1016/j.ijcard.2019.06.034DOI Listing
January 2020

Comparison of Routine Versus Selective Glycoprotein IIb/IIIa Inhibitors Usage in Primary Percutaneous Coronary Intervention (from the British Cardiovascular Interventional Society).

Am J Cardiol 2019 08 9;124(3):373-380. Epub 2019 May 9.

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK; Division of Cardiovascular Medicine, University of Cambridge, Cambridge, UK. Electronic address:

The role of glycoprotein IIb/IIIa inhibitors (GPI) in primary percutaneous coronary intervention (PPCI) remains uncertain. Previous analyses compare PPCI outcomes with clopidogrel plus GPI, versus without GPI. This does not reflect modern contemporary PPCI practice with ticagrelor or prasugrel. Nor does it answer the important question faced daily by PPCI operators: should GPI be used routinely or selectively? We aim to determine whether a strategy of routine use of GPI in contemporary PPCI practice is superior to selective GPI use. A total of 110,327 consecutive PPCIs performed in England were prospectively recorded in the British Cardiovascular Intervention Society Database (2009 to 2015). The cohort was divided into routine and selective GPI usage groups based on the PPCI operator's strategy, defined as GPI used in >75% and <25% PPCIs, respectively. Overall, GPI use declined from 73.1% to 43.3% of PPCIs. Routine compared with selective GPI usage was associated with lower all-cause 1-year mortality: 9.7% versus 11.0%, p < 0.001. There was a consistent survival benefit for routine GPI usage as compared with selective GPI usage: univariable analysis (hazard ratio = 0.88 [95% confidence interval 0.83 to 0.93], p < 0.001), multivariable analysis (hazard ratio = 0.82 [0.77 to 0.88], p < 0.001). For survival, there was no interaction between GPI usage and the type of P2Y12-inhibitor used. In conclusion, a strategy of routine GPI usage in patients who underwent PPCI was associated with lower all-cause mortality as compared with selective GPI usage. This benefit was maintained despite 44.3% of patients receiving prasugrel or ticagrelor.
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http://dx.doi.org/10.1016/j.amjcard.2019.05.010DOI Listing
August 2019

Author Correction: Percutaneous management of paravalvular leaks.

Nat Rev Cardiol 2019 Dec;16(12):760

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.

In the version of this article initially published online, the Paravalvular Leak Device (PLD; Occlutech) was incorrectly described as having a "proximal disc that is slightly larger than the distal disc", whereas the distal disc is actually slightly larger than the proximal disc. This error has been corrected for the HTML, PDF and print versions of the article.
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http://dx.doi.org/10.1038/s41569-019-0184-3DOI Listing
December 2019

Patent Foramen Ovale Closure in 2019.

Interv Cardiol 2019 Feb;14(1):34-41

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust Cambridge, UK.

Patent foramen ovale (PFO) is a common abnormality affecting between 20% and 34% of the adult population. For most people it is a benign finding; however, in some the PFO can open widely, enabling a paradoxical embolus to transit from the venous to arterial circulation, which is associated with stroke and systemic embolisation. Percutaneous closure of PFO in patients with cryptogenic stroke has been undertaken for a number of years, and a number of purpose-specific septal occluders have been marketed. Recent randomised controlled trials have demonstrated that closure of PFO in patients with cryptogenic stroke is associated with reduced rates of recurrent stroke. After a brief overview of the anatomy of a PFO, this review considers the evidence for PFO closure in cryptogenic stroke. The review also addresses other potential indications for closure, including systemic embolisation, decompression sickness, platypnoea-orthodeoxia syndrome and migraine with aura. It lays out the pre-procedural investigations and preparation for the procedure. Finally, it gives an overview of the procedure itself, including discussion of closure devices.
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http://dx.doi.org/10.15420/icr.2018.33.2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6406129PMC
February 2019

Coronary artery lesion phenotype in frail older patients with non-ST-elevation acute coronary syndrome undergoing invasive care.

EuroIntervention 2019 Jun 12;15(3):e261-e268. Epub 2019 Jun 12.

Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.

Aims: The association of frailty with coronary plaque phenotype among older patients with non-ST-elevation acute coronary syndrome (NSTEACS) is not known. The aim of this study was to evaluate the association of frailty with coronary plaque phenotype among older patients with NSTEACS.

Methods And Results: Older patients with NSTEACS who underwent invasive angiography were recruited. Frailty was measured using the Fried frailty score. Following angiography, patients underwent greyscale and virtual histology intravascular ultrasound (VH-IVUS) imaging. Of the 90 patients, 26 (28.9%) were robust, 49 (54.4%) patients were pre-frail, and 15 (16.7%) were frail. Mean age was 80.9±3.8 years; 59 (65.6%) were male. Compared to robust patients, the pre-frail group had a significantly greater presence of high-risk lesions including VH thin-cap fibroatheroma (TCFA, p=0.011), minimum lumen area (MLA) ≤4 mm2 (p=0.016), TCFA+MLA ≤4 mm2 (p=0.005), TCFA+plaque burden (PB) ≥70% (p=0.005) and TCFA+PB ≥70%+MLA ≤4 mm2 (p=0.003). By age- and sex-adjusted logistic regression analysis, frailty was found to be strongly and independently associated with the presence of TCFA (odds ratio [OR] 2.81, 95% confidence interval [CI]:1.06-7.48, p=0.039).

Conclusions: This is the first study to report the relationship between frailty phenotype and coronary plaque morphology among frail older NSTEACS patients. ClinicalTrials.gov Identifier: NCT01933581.
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http://dx.doi.org/10.4244/EIJ-D-18-00848DOI Listing
June 2019

Percutaneous management of paravalvular leaks.

Nat Rev Cardiol 2019 05;16(5):275-285

Department of Cardiology, Royal Papworth Hospital NHS Foundation Trust, Cambridge, UK.

Paravalvular leak (PVL) is a complication that occurs in 5-17% of patients after surgical prosthetic valve implantation. Whereas PVLs can be benign, some PVLs are associated with substantial morbidity and mortality. Percutaneous closure using occluders specifically designed to improve closure and reduce procedural complications has now become the first-line treatment for PVL. In this Review, we first detail the frequency and clinical consequences of PVL closure. The role of cardiac imaging in the assessment and management of PVL, including echocardiographic imaging and adjunctive techniques such as CT, is then discussed, together with important considerations for the percutaneous closure of PVL, such as access site and device selection. Finally, we summarize the clinical evidence for percutaneous closure of PVL, including large national registries from Ireland, Spain and the UK, as well as head-to-head data comparing this procedure with surgical closure.
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http://dx.doi.org/10.1038/s41569-018-0147-0DOI Listing
May 2019

High-Risk Atherosclerotic Plaque in Aberrant Circumflex Coronary Artery.

J Invasive Cardiol 2018 03;30(3):E26

Department of Cardiology, ABM University Health Board, Morriston Hospital, Swansea SA6 6NL, United Kingdom.

A 45-year-old man presented after an episode of central chest pain. Catheter angiography revealed an aberrant circumflex artery and high-grade stenosis in the mid RCA and proximal CX arteries. Previous case series have suggested that the retroaortic portion of aberrant circumflex arteries may be particularly prone to the development of atherosclerosis.
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March 2018

Effects of Patent Foramen Ovale Closure on Obstructive Sleep Apnea Syndrome: PCOSA Study.

Can J Cardiol 2017 12 12;33(12):1708-1715. Epub 2017 Sep 12.

RSSC, Papworth Hospital, Papworth Everard, United Kingdom.

Background: Previous studies have shown a higher prevalence of patent foramen ovale (PFO) in patients with obstructive sleep apnea syndrome (OSAS). Right to left shunting through a PFO may be encouraged by the respiratory physiology of OSAS, contributing to the disease pathophysiology. We assessed whether PFO closure would improve respiratory polygraphy parameters compared with baseline measurements in patients with OSAS.

Methods: Twenty-six patients with newly diagnosed OSAS and a moderate-large PFO (prevalence, 18% of 143 patients screened) were referred for PFO closure. The oxygen desaturation index (ODI), apnea-hypopnea index (AHI), Epworth Sleepiness Scale (ESS), 6-minute walk test (6MWT), and Sleep Apnea Quality of Life Index (SAQLI) results were compared in these patients at baseline (before continuous positive pressure ventilation [CPAP]) and at 6-month follow-up (after interrupting CPAP for 1 week).

Results: All PFOs were safely sealed at 6 months, as confirmed by repeated transthoracic echocardiography. The ODI (44.8 [interquartile range (IQR), 31.2-63.5) vs 42.3 [IQR, 34.0-60.8]; P = 0.89) and AHI (47.9 [IQR, 31.5-65.2] vs 42.3 [IQR, 32.1-63]; P = 0.99) did not change after PFO closure nor did the 6MWT, although the ESS (13.0 [IQR, 12.0-16.8] vs 6.0 [IQR, 4.0-8.8]; P < 0.001) and the SAQLI (3.4 [IQR, 2.8-4.3] vs 4.4 [IQR, 3.9-5.3]; P < 0.001) did improve.

Conclusions: The prevalence of PFO in OSAS appears to be no higher than that in the general population. Although PFO closure is safe and effective, it did not improve respiratory polygraphy measures of OSAS severity. The improvement in the ESS and SAQLI likely reflect residual benefits from CPAP.
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http://dx.doi.org/10.1016/j.cjca.2017.09.005DOI Listing
December 2017

Coronary CT angiography features of ruptured and high-risk atherosclerotic plaques: Correlation with intra-vascular ultrasound.

J Cardiovasc Comput Tomogr 2017 Nov 5;11(6):455-461. Epub 2017 Sep 5.

Division of Cardiovascular Medicine, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

Background: Features of ruptured and high-risk plaque have been described on coronary computed tomography angiography (coronary CTA), but not systematically assessed against intravascular ultrasound (IVUS). We examined the ability of coronary CTA to identify IVUS defined ruptured plaque and Virtual Histology Intravascular Ultrasound (VH-IVUS) defined thin-cap fibroatheroma (TCFA).

Methods: Sixty-three patients (32 with acute coronary syndrome and 31 with stable angina) underwent coronary CTA, IVUS and VH-IVUS. Plaque rupture on CTA was defined as intra-plaque contrast and its frequency compared with IVUS-defined plaque rupture. We then examined the relationship of conventional coronary CTA high-risk features (low attenuation plaque, positive remodeling, spotty calcification and the Napkin-Ring sign) in VH-IVUS-defined TCFA. We compared these with a novel index based on quantifying the ratio of necrotic core to fibrous plaque using x-ray attenuation cut-offs derived from the relationship of plaque to luminal contrast attenuation.

Results: Of the 71 plaques interrogated with IVUS, 39 were ruptured. Coronary CTA correctly detected 13-ruptured plaques with 3 false positives giving high specificity (91%) but low sensitivity (33%). None of the conventional coronary CTA high-risk features were significantly more frequent in the higher-risk (VH-IVUS defined thin-cap) compared with thick-cap fibroatheroma. However, the new index (necrotic core/fibrous plaque ratio) was higher in thin-cap (mean 0.90) vs. thick-cap fibroatheroma (mean 0.59), p < 0.05.

Conclusions: Compared with intravascular ultrasound, coronary CTA identifies ruptured plaque with good specificity but poor sensitivity. We have identified a novel high-risk feature on coronary CTA (necrotic core/fibrous plaque ratio that is associated with VH-IVUS defined-TCFA.
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http://dx.doi.org/10.1016/j.jcct.2017.09.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725309PMC
November 2017

Plaque Rupture in Coronary Atherosclerosis Is Associated With Increased Plaque Structural Stress.

JACC Cardiovasc Imaging 2017 12 19;10(12):1472-1483. Epub 2017 Jul 19.

Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom. Electronic address:

Objectives: The aim of this study was to identify the determinants of plaque structural stress (PSS) and the relationship between PSS and plaques with rupture.

Background: Plaque rupture is the most common cause of myocardial infarction, occurring particularly in higher risk lesions such as fibroatheromas. However, prospective intravascular ultrasound-virtual histology studies indicate that <10% higher risk plaques cause clinical events over 3 years, indicating that other factors also determine plaque rupture. Plaque rupture occurs when PSS exceeds its mechanical strength; however, the determinants of PSS and its association with plaques with proven rupture are not known.

Methods: We analyzed plaque structure and composition in 4,053 virtual histology intravascular ultrasound frames from 32 fibroatheromas with rupture from the intravascular ultrasound-virtual histology in Vulnerable Atherosclerosis study and 32 fibroatheromas without rupture on optical coherence tomography from a stable angina cohort. Mechanical loading in the periluminal region was estimated by calculating maximum principal PSS by finite element analysis.

Results: PSS increased with increasing lumen area (r = 0.46; p = 0.001), lumen eccentricity (r = 0.32; p = 0.001), and necrotic core ≥10% (r = 0.12; p = 0.001), but reduced when dense calcium was ≥10% (r = -0.12; p = 0.001). Ruptured fibroatheromas showed higher PSS (133 kPa [quartiles 1 to 3: 90 to 191 kPa] vs. 104 kPa [quartiles 1 to 3: 75 to 142 kPa]; p = 0.002) and variation in PSS (55 kPa [quartiles 1 to 3: 37 to 75 kPa] vs. 43 kPa [quartiles 1 to 3: 34 to 59 kPa]; p = 0.002) than nonruptured fibroatheromas, with rupture primarily occurring either proximal or immediately adjacent to the minimal luminal area (87.5% vs. 12.5%; p = 0.001). PSS was higher in segments proximal to the rupture site (143 kPa [quartiles 1 to 3: 101 to 200 kPa] vs. 120 kPa [quartiles 1 to 3: 78 to 180 kPa]; p = 0.001) versus distal segments, associated with increased necrotic core (19.1% [quartiles 1 to 3: 11% to 29%] vs. 14.3% [quartiles 1 to 3: 8% to 23%]; p = 0.001) but reduced fibrous/fibrofatty tissue (63.6% [quartiles 1 to 3: 46% to 78%] vs. 72.7% [quartiles 1 to 3: 54% to 86%]; p = 0.001). PSS >135 kPa was a good predictor of rupture in higher risk regions.

Conclusions: PSS is determined by plaque composition, plaque architecture, and lumen geometry. PSS and PSS variability are increased in plaques with rupture, particularly at proximal segments. Incorporating PSS into plaque assessment may improve identification of rupture-prone plaques.
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http://dx.doi.org/10.1016/j.jcmg.2017.04.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5725311PMC
December 2017

Inflammatory Differences in Plaque Erosion and Rupture in Patients With ST-Segment Elevation Myocardial Infarction.

J Am Heart Assoc 2017 May 3;6(5). Epub 2017 May 3.

Norfolk and Norwich University Hospital, Norwich, United Kingdom

Background: Plaque erosion causes 30% of ST-segment elevation myocardial infarctions, but the underlying cause is unknown. Inflammatory infiltrates are less abundant in erosion compared with rupture in autopsy studies. We hypothesized that erosion and rupture are associated with significant differences in intracoronary cytokines in vivo.

Methods And Results: Forty ST-segment elevation myocardial infarction patients with <6 hours of chest pain were classified as ruptured fibrous cap (RFC) or intact fibrous cap (IFC) using optical coherence tomography. Plasma samples from the infarct-related artery and a peripheral artery were analyzed for expression of 102 cytokines using arrays; results were confirmed with ELISA. Thrombectomy samples were analyzed for differential mRNA expression using quantitative real-time polymerase chain reaction. Twenty-three lesions were classified as RFC (58%), 15 as IFC (38%), and 2 were undefined (4%). In addition, 12% (12 of 102) of cytokines were differentially expressed in both coronary and peripheral plasma. I-TAC was preferentially expressed in RFC (significance analysis of microarrays adjusted <0.001; ELISA IFC 10.2 versus RFC 10.8 log pg/mL; =0.042). IFC was associated with preferential expression of epidermal growth factor (significance analysis of microarrays adjusted <0.001; ELISA IFC 7.42 versus RFC 6.63 log pg/mL, =0.036) and thrombospondin 1 (significance analysis of microarrays adjusted =0.03; ELISA IFC 10.4 versus RFC 8.65 log ng/mL, =0.0041). Thrombectomy mRNA showed elevated I-TAC in RFC (=0.0007) epidermal growth factor expression in IFC (=0.0264) but no differences in expression of thrombospondin 1.

Conclusions: These results demonstrate differential intracoronary cytokine expression in RFC and IFC. Elevated thrombospondin 1 and epidermal growth factor may play an etiological role in erosion.
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http://dx.doi.org/10.1161/JAHA.117.005868DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5524113PMC
May 2017

Patent foramen ovale presenting as visual loss.

JRSM Open 2016 Jan 1;8(1):2054270416669302. Epub 2016 Dec 1.

Department of Ophthalmology, Queen Elizabeth Hospital Birmingham, University Hospitals Birmingham NHS Foundation Trust, Birmingham B15 2TH, UK; Academic Unit of Ophthalmology, Institute of Inflammation and Ageing, University of Birmingham, Birmingham B15 2WB, UK; Centre for Rare Diseases, Institute of Translational Medicine, Birmingham Health Partners, Birmingham B15 2TH, UK.

Retinal artery occlusion in an otherwise healthy, young patient is rare. In this context it is important to consider patent foramen ovale as a differential. Early referral to a cardiology specialist for diagnosis and treatment is important for preventing further ocular and non-ocular events.
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http://dx.doi.org/10.1177/2054270416669302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5298438PMC
January 2016

Assessing flow limitation in patients with stable coronary artery disease.

BMJ 2016 Oct 20;355:i5534. Epub 2016 Oct 20.

Department of Cardiology, Papworth Hospital, Cambridge, UK.

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http://dx.doi.org/10.1136/bmj.i5534DOI Listing
October 2016

The Role of Virtual Histology Intravascular Ultrasound in the Identification of Coronary Artery Plaque Vulnerability in Acute Coronary Syndromes.

Cardiol Rev 2016 Nov/Dec;24(6):303-309

From the *Institute of Cellular Medicine, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, United Kingdom; †Cardiothoracic Centre, Freeman Hospital, Newcastle upon Tyne Hospitals National Health Service Foundation Trust, Newcastle upon Tyne, United Kingdom; ‡Volcano Corporation, San Diego, CA; §Department of Biomedical Engineering, Cleveland Clinic, Cleveland, OH; ¶Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom; ‖Department of Cardiology, Thorax Institute, Hospital Clinic, University of Barcelona, Barcelona, Spain; and **Division of Cardiology, Cardiovascular Research Foundation, New York, NY.

Markers of coronary plaque vulnerability, such as a high lipid burden, increased inflammatory activity, and a thin fibrous cap, have been identified in histological studies. In vivo, grayscale intravascular ultrasound (IVUS) provides more in-depth information on coronary artery plaque burden than conventional angiography but is unable to accurately distinguish between noncalcific tissue types within the plaque. An analysis of IVUS radiofrequency backscatter based on spectral pattern recognition, such as virtual histology IVUS, allows detailed scrutiny of plaque composition and classification of coronary lesions. This review discusses the virtual histology IVUS technology and its accuracy in identifying vulnerable plaque features, focusing on its use in predicting patient outcomes after acute coronary syndrome, and its limitations in clinical practice.
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http://dx.doi.org/10.1097/CRD.0000000000000100DOI Listing
March 2017

Closure of a coronary artery: coronary sinus fistula.

EuroIntervention 2016 10 10;12(8):e1009. Epub 2016 Oct 10.

Department of Cardiology, Queen Elizabeth Hospital, Birmingham, United Kingdom.

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http://dx.doi.org/10.4244/EIJV12I8A164DOI Listing
October 2016

Percutaneous Device Closure of Paravalvular Leak: Combined Experience From the United Kingdom and Ireland.

Circulation 2016 Sep 1;134(13):934-44. Epub 2016 Sep 1.

From Papworth Hospital NHS Foundation Trust, Cambridge, United Kingdom (P.A.C., L.S., W.R.D., B.S.R.); Queen Elizabeth Hospital, University Hospitals Birmingham, United Kingdom (P.A.C., P.L., P.C., J.d.G.); Institute of Translational Medicine, University of Birmingham, United Kingdom (P.A.C., P.C.); Royal Infirmary of Edinburgh, Edinburgh, United Kingdeom (D.B.N.); Imperial College NHS Trust, London, United Kingdom (I.S.M.); Evelina Children's Hospital, London, United Kingdom (S.A.Q., G.M.); The Heart Hospital, London, United Kingdom (M.M.); Nottingham University Hospital, Nottingham, United Kingdom (R.H., H.R.K.); Bristol Heart Institute, Bristol, United Kingdom (M.T., Y.I.); University Hospital Coventry, Coventry, United Kingdom (M.B.); Mater Misericordiae University Hospital, Dublin, Ireland (K.P.W.); Mater Private Hospital, Dublin, Ireland (I.C.); Liverpool Heart and Chest Hospital, Liverpool, United Kingdom (L.M., S.K.A.); Golden Jubilee National Hospital, Glasgow, United Kingdom (N.L.W.); Leeds General Infirmary, Leeds, United Kingdom (J.T.); Royal Victoria Hospital, Belfast, United Kingdom (M.S.S.); Manchester Royal Infirmary, Manchester, United Kingdom (V.S.M.); Castle Hill Hospital, Hull, United Kingdom (A.H.); King's College London, United Kingdom (P.A.M.); John Radcliffe Hospital, Oxford, United Kingdom (M.J.D., J.O.M.O., O.O.); and Royal Sussex County Hospital, Brighton, United Kingdom (S.S.C., D.H.-S.).

Background: Paravalvular leak (PVL) occurs in 5% to 17% of patients following surgical valve replacement. Percutaneous device closure represents an alternative to repeat surgery.

Methods: All UK and Ireland centers undertaking percutaneous PVL closure submitted data to the UK PVL Registry. Data were analyzed for association with death and major adverse cardiovascular events (MACE) at follow-up.

Results: Three hundred eight PVL closure procedures were attempted in 259 patients in 20 centers (2004-2015). Patient age was 67±13 years; 28% were female. The main indications for closure were heart failure (80%) and hemolysis (16%). Devices were successfully implanted in 91% of patients, via radial (7%), femoral arterial (52%), femoral venous (33%), and apical (7%) approaches. Nineteen percent of patients required repeat procedures. The target valve was mitral (44%), aortic (48%), both (2%), pulmonic (0.4%), or transcatheter aortic valve replacement (5%). Preprocedural leak was severe (61%), moderate (34%), or mild (5.7%) and was multiple in 37%. PVL improved postprocedure (P<0.001) and was none (33.3%), mild (41.4%), moderate (18.6%), or severe (6.7%) at last follow-up. Mean New York Heart Association class improved from 2.7±0.8 preprocedure to 1.6±0.8 (P<0.001) after a median follow-up of 110 (7-452) days. Hospital mortality was 2.9% (elective), 6.8% (in-hospital urgent), and 50% (emergency) (P<0.001). MACE during follow-up included death (16%), valve surgery (6%), late device embolization (0.4%), and new hemolysis requiring transfusion (1.6%). Mitral PVL was associated with higher MACE (hazard ratio [HR], 1.83; P=0.011). Factors independently associated with death were the degree of persisting leak (HR, 2.87; P=0.037), New York Heart Association class (HR, 2.00; P=0.015) at follow-up and baseline creatinine (HR, 8.19; P=0.001). The only factor independently associated with MACE was the degree of persisting leak at follow-up (HR, 3.01; P=0.002).

Conclusion: Percutaneous closure of PVL is an effective procedure that improves PVL severity and symptoms. Severity of persisting leak at follow-up is independently associated with both MACE and death. Percutaneous closure should be considered as an alternative to repeat surgery.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.116.022684DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6485596PMC
September 2016

Plaque Structural Stress Estimations Improve Prediction of Future Major Adverse Cardiovascular Events After Intracoronary Imaging.

Circ Cardiovasc Imaging 2016 06;9(6)

From the Division of Cardiovascular Medicine (A.J.B., P.A.C., N.K.R., O.H., D.R.O., C.C., M.R.B.), Department of Radiology (Z.T., Y.H., J.H.G.), and Department of Engineering (Z.T.), University of Cambridge, United Kingdom; MonashHEART, Monash Medical Centre, Clayton, Australia (N.N.); and Department of Interventional Cardiology (P.A.C., S.P.H., N.E.J.W.) and Department of Pathology (M.G.), Papworth Hospital NHS Trust, United Kingdom.

Background: Although plaque rupture is responsible for most myocardial infarctions, few high-risk plaques identified by intracoronary imaging actually result in future major adverse cardiovascular events (MACE). Nonimaging markers of individual plaque behavior are therefore required. Rupture occurs when plaque structural stress (PSS) exceeds material strength. We therefore assessed whether PSS could predict future MACE in high-risk nonculprit lesions identified on virtual-histology intravascular ultrasound.

Methods And Results: Baseline nonculprit lesion features associated with MACE during long-term follow-up (median: 1115 days) were determined in 170 patients undergoing 3-vessel virtual-histology intravascular ultrasound. MACE was associated with plaque burden ≥70% (hazard ratio: 8.6; 95% confidence interval, 2.5-30.6; P<0.001) and minimal luminal area ≤4 mm(2) (hazard ratio: 6.6; 95% confidence interval, 2.1-20.1; P=0.036), although absolute event rates for high-risk lesions remained <10%. PSS derived from virtual-histology intravascular ultrasound was subsequently estimated in nonculprit lesions responsible for MACE (n=22) versus matched control lesions (n=22). PSS showed marked heterogeneity across and between similar lesions but was significantly increased in MACE lesions at high-risk regions, including plaque burden ≥70% (13.9±11.5 versus 10.2±4.7; P<0.001) and thin-cap fibroatheroma (14.0±8.9 versus 11.6±4.5; P=0.02). Furthermore, PSS improved the ability of virtual-histology intravascular ultrasound to predict MACE in plaques with plaque burden ≥70% (adjusted log-rank, P=0.003) and minimal luminal area ≤4 mm(2) (P=0.002). Plaques responsible for MACE had larger superficial calcium inclusions, which acted to increase PSS (P<0.05).

Conclusions: Baseline PSS is increased in plaques responsible for MACE and improves the ability of intracoronary imaging to predict events. Biomechanical modeling may complement plaque imaging for risk stratification of coronary nonculprit lesions.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.004172DOI Listing
June 2016

Percutaneous Closure of Paravalvular Leaks: A Systematic Review.

J Interv Cardiol 2016 Aug 31;29(4):382-92. Epub 2016 May 31.

University Hospital of Salamanca, IBSAL, Salamanca, Spain.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with the implantation of mechanical or bioprosthetic surgical valves and more recently recognized with transcatheter aortic valves implantation (TAVI). A significant number of patients will present with symptoms of congestive heart failure or haemolytic anaemia due to PVL and need further surgical or percutaneous treatment. Until recently, surgery has been the only available therapy for the treatment of clinically significant PVLs despite the significant morbidity and mortality associated with re-operation. Percutaneous treatment of PVLs has emerged as a safe and less invasive alternative, with low complication rates and high technical and clinical success rates. However, it is a complex procedure, which needs to be performed by an experienced team of interventional cardiologists and echocardiographers. This review discusses the current understanding of PVLs, including the utility of imaging techniques in PVL diagnosis and treatment, and the principles, outcomes and complications of transcatheter therapy of PVLs.
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http://dx.doi.org/10.1111/joic.12295DOI Listing
August 2016

Geographical miss is associated with vulnerable plaque and increased major adverse cardiovascular events in patients with myocardial infarction.

Catheter Cardiovasc Interv 2016 Sep 3;88(3):340-7. Epub 2015 Nov 3.

Division of Cardiovascular Medicine, University of Cambridge, Cambridge, United Kingdom.

Objectives: To determine the incidence, characteristics, and outcomes associated with geographical miss (GM) of plaque.

Background: GM describes plaques that are incompletely covered following stenting, with GM thought to be associated with worse clinical outcomes. However, the incidence and characteristics of intravascular ultrasound (IVUS)-defined GM plaques have never been studied and the relationship between GM with both short and long-term clinical events is unknown.

Methods: One hundred and seventy patients with stable angina (n = 100) or myocardial infarction (MI) (n = 70) underwent virtual-histology IVUS (VH-IVUS) prior to, and following, percutaneous coronary intervention (PCI). GM was defined as three consecutive uncovered VH frames, either proximal or distal to the stented segment with plaque burden >40%. MACE was defined as a composite of death, myocardial infarction, unplanned revascularization, or hospitalization for angina.

Results: In total, 245 plaques underwent PCI with 80 (32.7%) displaying evidence of GM (69 patients). GM was associated with increased plaque volume (p < 0.001), % necrotic core, and dense calcium (both p < 0.001) and VH-defined thin-cap fibroatheroma (VH-TCFA) (p = 0.01). GM was not associated with increased periprocedural MI (p = 0.15) or inflammatory cytokine release. At follow-up, 42 MACE occurred in 28 patients (median 1,115 days). MACE was attributable to 8/80 (10%) plaques with and 7/165 (4.2%) plaques without GM (log-rank p = 0.11). GM was associated with increased MACE in patients presenting with MI (p = 0.015), but not for those with stable angina (p = 0.94).

Conclusions: GM is common after PCI and associated with more vulnerable plaque composition/subtype. GM may confer a worse prognosis in patients undergoing PCI for MI. © 2015 Wiley Periodicals, Inc.
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http://dx.doi.org/10.1002/ccd.26275DOI Listing
September 2016

Direct Comparison of Virtual-Histology Intravascular Ultrasound and Optical Coherence Tomography Imaging for Identification of Thin-Cap Fibroatheroma.

Circ Cardiovasc Imaging 2015 Oct;8(10):e003487

From the Division of Cardiovascular Medicine (A.J.B., D.R.O., C.C., P.A.C., M.R.B.), Department of Radiology (Z.T.), and Department of Engineering (Z.T.), University of Cambridge, Cambridge, United Kingdom; Health Services Research Unit, Usher Institute of Population Health Sciences and Informatics, College of Medicine and Veterinary Medicine. University of Edinburgh, Edinburgh, United Kingdom (R.A.P.); and Departments of Interventional Cardiology (S.P.H., N.E.J.W.) and Pathology (M.G.), Papworth Hospital NHS Trust, Cambridge, United Kingdom.

Background: Although rupture of thin-cap fibroatheroma (TCFA) underlies most myocardial infarctions, reliable TCFA identification remains challenging. Virtual-histology intravascular ultrasound (VH-IVUS) and optical coherence tomography (OCT) can assess tissue composition and classify plaques. However, direct comparisons between VH-IVUS and OCT are lacking and it remains unknown whether combining these modalities improves TCFA identification.

Methods And Results: Two hundred fifty-eight regions-of-interest were obtained from autopsied human hearts, with plaque composition and classification assessed by histology and compared with coregistered ex vivo VH-IVUS and OCT. Sixty-seven regions-of-interest were classified as fibroatheroma on histology, with 22 meeting criteria for TCFA. On VH-IVUS, plaque (10.91±4.82 versus 8.42±4.57 mm(2); P=0.01) and necrotic core areas (1.59±0.99 versus 1.03±0.85 mm(2); P=0.02) were increased in TCFA versus other fibroatheroma. On OCT, although minimal fibrous cap thickness was similar (71.8±44.1 μm versus 72.6±32.4; P=0.30), the number of continuous frames with fibrous cap thickness ≤85 μm was higher in TCFA (6.5 [1.75-11.0] versus 2.0 [0.0-7.0]; P=0.03). Maximum lipid arc on OCT was an excellent discriminator of fibroatheroma (area under the curve, 0.92; 95% confidence interval, 0.87-0.97) and TCFA (area under the curve, 0.86; 95% confidence interval, 0.81-0.92), with lipid arc ≥80° the optimal cut-off value. Using existing criteria, the sensitivity, specificity, and diagnostic accuracy for TCFA identification was 63.6%, 78.1%, and 76.5% for VH-IVUS and 72.7%, 79.8%, and 79.0% for OCT. Combining VH-defined fibroatheroma and fibrous cap thickness ≤85 μm over 3 continuous frames improved TCFA identification, with diagnostic accuracy of 89.0%.

Conclusions: Both VH-IVUS and OCT can reliably identify TCFA, although OCT accuracy may be improved using lipid arc ≥80° and fibrous cap thickness ≤85 μm over 3 continuous frames. Combined VH-IVUS/OCT imaging markedly improved TCFA identification.
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http://dx.doi.org/10.1161/CIRCIMAGING.115.003487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4596008PMC
October 2015

Ischaemic heart disease - a selected review of recent developments.

Curr Opin Cardiol 2015 Nov;30(6):657-62

aInstitute of Translational Medicine, Queen Elizabeth Hospital, University Hospitals Birmingham NHS Foundation Trust bUniversity of Birmingham, Birmingham, UK.

Purpose Of Review: The purpose of this review is to highlight important and interesting advances in the field of ischaemic heart disease that have occurred over the last 18 months. It is focused on research that is likely to lead to changes in clinical practice.

Recent Findings: There is new evidence on appropriate pharmacotherapy during angioplasty in both stable and unstable patients. The use of pressure wire assessment has been shown to improve patient outcome. The management of patients with ST elevation myocardial infarction (STEMI) is likely to change with a reduction in the use of manual thrombectomy and an increase in the treatment of nonculprit disease.

Summary: The optimal duration of dual antiplatelet therapy in percutaneous coronary intervention remains an intensely debated topic with contradictory results from major trials. Pressure wire guided coronary intervention reduces the need for urgent revascularization. The use of fractional flow reserve computed tomography has the potential to revolutionize functional testing. The treatment of patients presenting with ST elevation myocardial infarction is likely to change dramatically. Heparin with bailout glycoprotein IIbIIIa-inhibitor (GPIIbIIIa-I) appears superior to bivalirudin alone, although there is no longer a role for routine manual thrombectomy. Multivessel PCI to establish complete revascularization may become the gold standard in patients presenting with STEMI, although larger trials are needed. Novel therapies are being devised for the treatment of patients with intractable angina, but further work is required in this area.
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http://dx.doi.org/10.1097/HCO.0000000000000230DOI Listing
November 2015

Role of percutaneous mitral valve repair in the contemporary management of mitral regurgitation.

Heart 2015 Oct 22;101(19):1531-9. Epub 2015 Jun 22.

Brighton University Hospital.

Percutaneous mitral valve (MV) repair has been performed in over 20,000 patients worldwide. As clinical experience in this technique grows indications for its use are being defined. Mitral regurgitation (MR) encompasses a complex heterogeneous group and its treatment is governed by determining a clear understanding of the underlying aetiology. Surgical MV repair remains the gold standard therapy for severe MR. However in select groups of high-risk surgical patients, a percutaneous approach to MV repair is establishing its role. This review gives an overview of the published data in percutaneous MV repair and its impact on the contemporary management of MR.
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http://dx.doi.org/10.1136/heartjnl-2014-306256DOI Listing
October 2015

Dual-energy computed tomography imaging to determine atherosclerotic plaque composition: a prospective study with tissue validation.

J Cardiovasc Comput Tomogr 2014 May-Jun;8(3):230-7. Epub 2014 May 2.

Division of Cardiovascular Medicine, University of Cambridge, ACCI, Hills Road, Cambridge, CB2 0QQ, UK. Electronic address:

Background: Identifying vulnerable coronary plaque with coronary CT angiography is limited by overlap between attenuation of necrotic core and fibrous plaque. Using x-rays with differing energies alters attenuation values of these components, depending on their material composition.

Objectives: We sought to determine whether dual-energy CT (DECT) improves plaque component discrimination compared with single-energy CT (SECT).

Methods: Twenty patients underwent DECT and virtual histology intravascular ultrasound (VH-IVUS). Attenuation changes at 100 and 140 kV for each plaque component were defined, using 1088 plaque areas co-registered with VH-IVUS. Hounsfield unit thresholds that best detected necrotic core were derived for SECT (conventional attenuation values) and for DECT (using dual-energy indices, defined as difference in Hounsfield unit values at the 2 voltages/their sum). Sensitivity of SECT and DECT to detect plaque components was determined in 77 segments from 7 postmortem coronary arteries. Finally, we examined 60 plaques in vivo to determine feasibility and sensitivity of clinical DECT to detect VH-IVUS-defined necrotic core.

Results: In contrast to conventional SECT, mean dual-energy indices of necrotic core and fibrous tissue were significantly different with minimal overlap of ranges (necrotic core, 0.007 [95% CI, -0.001 to 0.016]; fibrous tissue, 0.028 [95% CI, 0.016-0.050]; P < .0001). DECT increased diagnostic accuracy to detect necrotic core in postmortem arteries (sensitivity, 64%; specificity, 98%) compared with SECT (sensitivity, 50%; specificity, 94%). DECT sensitivity to detect necrotic core was lower when analyzed in vivo, although still better than SECT (45% vs 39%).

Conclusions: DECT improves the differentiation of necrotic core and fibrous plaque in ex vivo postmortem arteries. However, much of this improvement is lost when translated to in vivo imaging because of a reduction in image quality.
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http://dx.doi.org/10.1016/j.jcct.2014.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4070076PMC
February 2015

Percutaneous closure of postinfarction ventricular septal defect: in-hospital outcomes and long-term follow-up of UK experience.

Circulation 2014 Jun 25;129(23):2395-402. Epub 2014 Mar 25.

From the University Hospitals Birmingham National Health Service Foundation Trust, Birmingham, UK (P.A.C., P.L., J.d.G.); University of Cambridge, Cambridge, UK (P.A.C.); Papworth Hospital National Health Service Foundation Trust, Cambridge, UK (P.A.C., B.S.R., L.M.S.); Sussex Cardiac Centre, Brighton and Sussex University Hospitals, Brighton, UK (J.C., D.W., D.H.-S.); Edinburgh Royal Infirmary, Edinburgh, UK (D.N.); The Heart Hospital, University College London, London, UK (M.J.M.); Imperial College Healthcare National Health Service Trust, London, UK (I.M.); University Hospitals Bristol National Health Service Foundation Trust, Bristol, UK (M.T.); Heart and Lung Centre, New Cross Hospital, Wolverhampton, UK (S.K.); University Hospital Southampton National Health Service Foundation Trust, Southampton, UK (G.R.V.); Walsgrave Hospital Coventry, Coventry, UK (M.B.); University Hospital North Staffordshire National Health Service Trust, Stoke-on-Trent, UK (R.B.); Leeds Teaching Hospitals National Health Service Trust, Leeds, UK (J.T.); King's College Hospital National Health Service Foundation Trust, London, UK (J.B., P.M.); Liverpool Heart and Chest Hospitals National Health Service Foundation Trust, Liverpool, UK (L.M.); and University Hospital of South Manchester, Manchester, UK (B.B.).

Background: Postinfarction ventricular septal defect carries a grim prognosis. Surgical repair offers reasonable outcomes in patients who survive a healing phase. Percutaneous device implantation represents a potentially attractive early alternative.

Methods And Results: Postinfarction ventricular septal defect closure was attempted in 53 patients from 11 centers (1997-2012; aged 72±11 years; 42% female). Nineteen percent had previous surgical closure. Myocardial infarction was anterior (66%) or inferior (34%). Time from myocardial infarction to closure procedure was 13 (first and third quartiles, 5-54) days. Devices were successfully implanted in 89% of patients. Major immediate complications included procedural death (3.8%) and emergency cardiac surgery (7.5%). Immediate shunt reduction was graded as complete (23%), partial (62%), or none (15%). Median length of stay after the procedure was 5.0 (2.0-9.0) days. Fifty-eight percent survived to discharge and were followed up for 395 (63-1522) days, during which time 4 additional patients died (7.5%). Factors associated with death after postinfarction ventricular septal defect closure included the following: age (hazard ratio [HR]=1.04; P=0.039), female sex (HR=2.33; P=0.043), New York Heart Association class IV (HR=4.42; P=0.002), cardiogenic shock (HR=3.75; P=0.003), creatinine (HR=1.007; P=0.003), defect size (HR=1.09; P=0.026), inotropes (HR=4.18; P=0.005), and absence of revascularization therapy for presenting myocardial infarction (HR=3.28; P=0.009). Prior surgical closure (HR=0.12; P=0.040) and immediate shunt reduction (HR=0.49; P=0.037) were associated with survival.

Conclusions: Percutaneous closure of postinfarction ventricular septal defect is a reasonably effective treatment for these extremely high-risk patients. Mortality remains high, but patients who survive to discharge do well in the longer term.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.113.005839DOI Listing
June 2014