Search

Presents information on a study that outlined the design philosophy and objectives for producing phase-optimized trilayer structures for magneto-optic enhancement of the polar Kerr effect. Experimental procedure; Theoretical results; Conclusion.

Objectives: Treatment options for coronary chronic total occlusions (CTO) are limited, with low historical success rates from percutaneous coronary intervention (PCI). We report procedural outcomes of CTO PCI from 7 centres with dedicated CTO operators trained in hybrid approaches comprising antegrade/retrograde wire escalation (AWE/RWE) and dissection re-entry (ADR/RDR) techniques.Methods: Clinical and procedural data were collected from consecutive unselected patients with CTO between 2012 and 2014. Lesion complexity was graded by the Multicentre CTO Registry of Japan (J-CTO) score, with ≥2 defined as complex. Success was defined as thrombolysis in myocardial infarction 3 flow with <30% residual stenosis, subclassified as at first attempt or overall. Inhospital complications and 30-day major adverse cardiovascular events (MACEs, death/myocardial infarction/unplanned target vessel revascularisation) were recorded.Results: 1156 patients were included. Despite high complexity (mean J-CTO score 2.5±1.3), success rates were 79% (first attempt) and 90% (overall) with 30-day MACE of 1.6%. AWE was highly effective in less complex lesions (J-CTO ≤1 94% success vs 79% in J-CTO score ≥2). ADR/RDR was used more commonly in complex lesions (J-CTO≤1 15% vs J-CTO ≥2 56%). Need for multiple approaches during each attempt increased with lesion complexity (17% J-CTO ≤1 vs 48% J-CTO ≥2). Lesion modification ('investment procedures') at the end of unsuccessful first attempts increased the chance of subsequent success (96% vs 71%).Conclusions: Hybrid-trained operators can achieve overall success rates of 90% in real world practice with acceptable MACE. Use of dissection re-entry and investment procedures maintains high success rates in complex lesions. The hybrid approach represents a significant advance in CTO treatment. [ABSTRACT FROM AUTHOR]

The embryological development of the superior vena cava (SVC) is complex. If the left common cardinal vein fails to occlude it can, along with the left duct of Cuvier form a left SVC, which frequently drains into the coronary sinus. This may result in abnormalities in the anatomy of this structure. A persistent left SVC occurs in 0·5% of the normal population, and 3% to 4·3% of patients with congenital heart anomalies.The pacemaking tissue of the heart is derived from two sites near the progenitors of the superior vena cava. The right-sided site forms the sinoatrial node, the left-sided site is normally carried down to an area near the coronary sinus.Out of 300 patients with cardiac rhythm abnormalities, who have undergone electrophysiological studies (EPS), or permanent pacemaker insertion (PPI), we identified 12 patients with cardiac conduction abnormalities and anomalies of venous drainage. Anomalies of the coronary sinus may be associated with abnormalities of the conduction system of the heart. This may be due to the close proximity of the coronary sinus to the final position of the left-sided primitive pacemaking tissue. In our series of 300 patients, 4% had an associated left SVC, a similar incidence to that found in previous studies of congenital heart disease. [ABSTRACT FROM PUBLISHER]

Background: Manipulation of total homocysteine concentration with oral methionine is associated with impairment of endothelial-dependent vasodilation. This may be caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant vitamin and free radical scavenger. We hypothesised that if the impairment of endothelial function related to experimental hyperhomocysteinaemia was free radically mediated then co-administration of vitamin C should prevent this.Methods: Ten healthy adults took part in this crossover study. Endothelial function was determined by measuring forearm blood flow (FBF) in response to intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg) plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink plus placebo tablets. Study drugs were administered at 9 am on each study date, a minimum of two weeks passed between each study. Homocysteine (tHcy) concentration was determined at baseline and after 4 hours. Endothelial function was determined at 4 hours. Responses to the vasoactive substances are expressed as the area under the curve of change in FBF from baseline. Data are mean plus 95% Confidence Intervals.Results: Following oral methionine tHcy concentration increased significantly versus placebo. At this time endothelial-dependent responses were significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were unchanged. Co-administration of vitamin C did not alter the increase in homocysteine or prevent the impairment of endothelial-dependent responses (31.4 [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo)Conclusions: This study demonstrates that methionine increased tHcy with impairment of the endothelial-dependent vasomotor responses. Administration of vitamin C did not prevent this impairment and our results do not support the hypothesis that the endothelial impairment is mediated by adverse oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Coronavirus disease 2019 has impacted upon the role and safety of healthcare workers, with the potential to have a lasting effect on their wellbeing. Limited research has been conducted during previous pandemics exploring how student healthcare workers are impacted as they study and train for their professional careers., Objective: The aim of the current study was to examine the specific impact of COVID-19 on the academic, clinical and personal experiences of healthcare students., Method: Undergraduate students across three year groups within the School of Health Sciences at Ulster University completed online Qualtrics surveys at three timepoints during one academic year (2020/2021). Quantitative survey data was downloaded from Qualtrics into SPSS Version 25 for descriptive analysis of each cross-sectional sample. Qualitative survey data was downloaded into text format, which was thematically analysed using content analysis., Results: 412 students completed the survey at Time 1 (October 2020), n = 309 at Time 2 (December 2020) and n = 259 at Time 3 (April 2021). Academically, the pandemic had mostly a negative impact on the learning environment, the development of practical skills, the assessment process and opportunities for peer learning and support. Students reported increased stress and challenges managing their workload and maintaining a sense of motivation and routine. Clinically, they felt unprepared by the university for placement where the pandemic had an increasingly negative impact over time on learning and skill development. In terms of personal experiences, despite the majority of students taking steps to keep physically and mentally well, negative impacts on friendships, mental wellbeing and concerns for family were reported. The pandemic had not impacted upon career choice for most students., Conclusion: Consideration must be given to the development of practical skills so students feel prepared for their professional careers given the practical nature of their roles. Programme coordinators should adopt a holistic approach to student wellbeing., Competing Interests: The authors have declared that no competing interests exist.

Coronary artery ectasia (CAE) is frequently encountered in clinical practice, conjointly with atherosclerotic CAD (CAD). Given the overlapping cardiovascular risk factors for patients with concomitant CAE and atherosclerotic CAD, a common underlying pathophysiology is often postulated. However, coronary artery ectasia may arise independently, as isolated (pure) CAE, thereby raising suspicions of an alternative mechanism. Herein, we review the existing evidence for the pathophysiology of CAE in order to help direct management strategies towards enhanced detection and treatment.

Objectives: The authors used the BCIS (British Cardiovascular Intervention Society) database to define the factors associated with percutaneous coronary intervention (PCI) procedural complexity., Background: Complex high-risk indicated percutaneous coronary intervention (CHIP-PCI) is an emerging concept that is poorly defined., Methods: The BCIS (British Cardiovascular Intervention Society) database was used to study all PCI procedures in the United Kingdom 2006-2016. A multiple logistic regression model was developed to identify variables associated with in-hospital major adverse cardiac or cerebrovascular events (MACCE) and to construct a CHIP score. The cumulative effect of this score on patient outcomes was examined., Results: A total of 313,054 patients were included. Seven patient factors (age ≥80 years, female sex, previous stroke, previous myocardial infarction, peripheral vascular disease, ejection fraction <30%, and chronic renal disease) and 6 procedural factors (rotational atherectomy, left main PCI, 3-vessel PCI, dual arterial access, left ventricular mechanical support, and total lesion length >60 mm) were associated with increased in-hospital MACCE and defined as CHIP factors. The mean CHIP score/case for all PCIs increased significantly from 1.06 ± 1.32 in 2006 to 1.49 ± 1.58 in 2016 (P < 0.001 for trend). A CHIP score of 5 or more was present in 2.5% of procedures in 2006 increasing to 5.3% in 2016 (P < 0.001 for trend). Overall in-hospital MACCE was 0.6% when the CHIP score was 0 compared with 1.2% with any CHIP factor present (P < 0.001). As the CHIP score increased, an exponential increase in-hospital MACCE was observed. The cumulative MACCE for procedures associated with a CHIP score 4+ or above was 3.2%, and for a CHIP score 5+ was 4.4%. All other adverse clinical outcomes were more likely as the CHIP score increased., Conclusions: Seven patient factors and 6 procedural factors were associated with adverse in-hospital MACCE and defined as CHIP factors. Use of a CHIP score might be a future target for risk modification., Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Developmental Dysplasia of the Hip (DDH) has been linked to high birth weight and packaging disorders, though the evidence is limited. This has implications on screening strategies. The aim of this study was to establish whether birth weight was truly associated with the incidence of DDH., Patients and Methods: This cohort study analysed the birth weights of all babies born at our institution over a 24 month period, between 01/01/2017 and 01/01/2019. Babies with DDH and those without DDH were compared. Babies were excluded if born before 38 weeks, had incomplete data or were a non-singleton pregnancy. Sub-analysis was performed for DDH severity (dysplastic versus subluxed/dislocated hips), breech presentation, gestational age, gender and ethnicity. Statistical analysis was performed using SPSS., Results: There were 10,113 babies born at our institution during the selected timeframe, of which 884 were excluded for prematurity, 336 for being non-singleton and 19 for incomplete data. This left 8874 for analysis, of which 95 babies had confirmed DDH. Both the Non-DDH and DDH data sets had normal distribution (Shapiro-Wilkes, p  = 0.308 and 0.629, respectively), with mean birth weights of 3477.7 g with DDH and 3492.8 g without DDH. No difference in birth weight was found (Independent T test, p  = 0.789). Females had a lower birth weight than males (3293.1 g versus 3416.6 g ( p  < 0.001)) yet have a higher incidence of DDH (ratio 6:1 in this dataset). No significant difference was found between birth weights of females with and without DDH ( p  = 0.068), nor between males with and without DDH ( p  = 0.513). There were no significant differences in birth weights even when only displaced hips were analysed ( p  = 0.543), nor according to breech presentation ( p  = 0.8). Longer gestation babies weighed more ( p  < 0.00001), yet showed no increase in DDH incidence ( p  = 0.64)., Conclusion: This study discredits the belief that DDH may be related to higher birth weight, thus casting doubt on the link to DDH being a packaging problem in utero. This, therefore, allows future research to prioritise the investigation of alternative aetiologies., Competing Interests: Conflict of InterestOn behalf of all authors, the corresponding author states that there is no conflict of interest., (© The Author(s) 2021.)

The authors developed a global chronic total occlusion crossing algorithm following 10 steps: 1) dual angiography; 2) careful angiographic review focusing on proximal cap morphology, occlusion segment, distal vessel quality, and collateral circulation; 3) approaching proximal cap ambiguity using intravascular ultrasound, retrograde, and move-the-cap techniques; 4) approaching poor distal vessel quality using the retrograde approach and bifurcation at the distal cap by use of a dual-lumen catheter and intravascular ultrasound; 5) feasibility of retrograde crossing through grafts and septal and epicardial collateral vessels; 6) antegrade wiring strategies; 7) retrograde approach; 8) changing strategy when failing to achieve progress; 9) considering performing an investment procedure if crossing attempts fail; and 10) stopping when reaching high radiation or contrast dose or in case of long procedural time, occurrence of a serious complication, operator and patient fatigue, or lack of expertise or equipment. This algorithm can improve outcomes and expand discussion, research, and collaboration., Competing Interests: Funding Support and Author Disclosures Dr Wu has received research funding from Abiomed, OrbusNeich, Asahi Intecc; has received consulting honoraria from Boston Scientific and Abbott Vascular; is a member of the board of directors for APCTO Club; and holds stock in Abbott Vascular. Dr Brilakis has received consulting and speaker honoraria from Abbott Vascular, the American Heart Association (associate editor, Circulation), Amgen, Biotronik, Boston Scientific, Cardiovascular Innovations Foundation (board of directors), ControlRad, CSI, Ebix, Elsevier, GE Healthcare, InfraRedx, Medtronic, Siemens, and Teleflex; has received research support from Regeneron and Siemens; is an owner of Hippocrates; and is a shareholder in MHI Ventures. Dr Mashayekhi has received consulting, speaker, and proctoring honoraria from Abbott Vascular, Asahi Intecc, AstraZeneca, Biotronik, Boston Scientific, Cardinal Health, Daiichi-Sankyo, Medtronic, Teleflex, and Terumo. Dr Tsuchikane is a consultant for Boston Scientific, Asahi Intecc, Nipro, and Kaneka. Dr Avran has received consulting, speaker, and proctoring honoraria from Asahi Intecc, Biotronik, Boston Scientific, Terumo, Alvimedica, and OrbusNeich. Dr Azzalini has received consulting fees from Abiomed and Teleflex. Dr Buller is global medical director of Teleflex. Dr Burke is a shareholder in Egg Medical and MHI Ventures. Dr Croce has received grants from Abbott, Takeda, Teleflex, and CSI; has received consulting honoraria from Abbott, BSCI, Biotronik, Philips, Abiomed, CSI, Takeda, and Cordis; and holds stock in Dyad Medical. Dr Damas de los Santos is a proctor, speaker, and consultant for Boston Scientific, Terumo, Abbott Vascular, and Biotronik. Dr Dens has consultancy contracts with Abbott, Boston Scientific, IMDS, Terumo, Topmedical (a distributor for Asahi); and is a chronic total occlusion proctor for Boston Scientific and Topmedical (Asahi). Dr di Mario has received research grants from Abbott, Amgen, Behring, Daiichi-Sankyo, Edwards, Medtronic, and Shockwave Medical. Dr Egred has received chronic total occlusion proctorship fees, speaker fees, honoraria, and grants from Abbott Vascular, Boston Scientific, Philips, Spectranetics, Vascular Perspectives, Merrill, Biotronik, and AstraZeneca. Dr Elbarouni has received speaker fees from Teleflex and Bayer. Dr ElGuindy has received consulting, speaker, and proctoring honoraria from Medtronic, Boston Scientific, Asahi Intecc, and Terumo. Dr Escaned has received personal fees from Abbott, Boston Scientific, Terumo, and Phillips. Dr Furkalo has a proctoring agreement with Medtronic; and has received speaker honoraria from Sanofi. Dr Garbo is a proctor and consultant for Philips Volcano, Boston Europe, Terumo Italy, and Europe Teleflex. Dr Hall has received speaker honoraria from Medtronic, OpSens Medical, and the Cardiovascular Innovations Foundation. Dr Hanna Quesada has received honoraria from Boston Scientific. Dr Harb is a consultant for Medtronic and Cardinal Health; and has received speaker honoraria from Cardinal Health and Terumo. Dr Harding has received speaker and consultancy fees from Boston Scientific, Medtronic, Bio-Excel, and Asahi Intecc. Dr Hatem is a member of the Speakers Bureau for Abbott, Boston Scientific, and Teleflex. Dr Hoye has received speaker fees from AstraZeneca and Sanofi. Dr Jaber has received proctoring fees from Abbott; and has received consulting, advisory board, and institutional funds from Medtronic. Dr Jaffer conducts sponsored research for Canon, Siemens, Teleflex, and Shockwave; is a consultant for Boston Scientific, Siemens, Biotronik, and Magenta Medical; and holds equity interest in Intravascular Imaging. Dr Jussila has a proctoring contract with Boston Scientific and EPS Vascular. Dr Kalyanasundaram has received fees from Abbott Vascular, Boston Scientific, Asahi Intecc, and Terumo. Dr Kandzari has received institutional research grant support from Abbott, Biotronik, Boston Scientific, Cardiovascular Systems, Medtronic, Teleflex, and OrbusNeich; Dr Karmpaliotis has received honoraria from Abbott Vascular and Boston Scientific; and holds equity in Saranas, Soundbite, and Traverse Vascular. Dr Kassem has received speaker honoraria from Boston Scientific, Abbott Vascular, GE, and Abiomed. Dr Khatri has received institutional research grant from Asahi Intecc and honoraria or consulting fees from Abbott Vascular, Boston Scientific, and Terumo. Dr Kornowski is a founder of NitiLoop. Dr Lamelas has received proctoring fees from Boston Scientific, Edwards Lifesciences, and Medtronic. Dr Lim has received educational support and honoraria from Asahi Intecc, Boston Scientific, Abbott Vascular, Kaneka, Biotronik, Alvimedica, Terumo, and Medtronic. Dr Lo has received speaker and proctoring honoraria from Bio-Excel, Boston Scientific, Abbott, and Terumo; and is a member of Medtronic’s advisory board. Dr Lombardi has received royalties and is a consultant for Asahi Intecc; is a consultant for Abiomed, Boston Scientific, Medtronic, Siemens, and Teleflex; and his spouse is an employee of Philips. Dr Maran is a consultant for Boston Scientific, Medtronic, and Philips. Dr Moses has received funding from Orchestra Biomedical and Ostial Corporation. Dr Munawar has received speaker and proctorship honoraria from Asahi Intecc, Terumo, Boston Scientific, Abbott Vascular, Toray, and Phillips. Dr Oksnes has proctoring contracts with Boston Scientific and EPS Vascular. Dr Olivecrona has received lecture honoraria from Abbott and Biotronik; and has received proctoring honoraria from EPS Vascular and Terumo. Dr Patel is a consultant for Abbott Vascular, Terumo, and Chiesi; and is a proctor for Medtronic. Dr Quadros has received honoraria from Boston Scientific; and has received research funding from Boston and Terumo. Dr Abi Rafeh is a proctor and consultant for Boston Scientific, Abbott, and Shockwave Medical. Dr Råmunddal has received consulting honoraria from EPS Vascular, Boston Scientific, and Abbott Vascular. Dr Riley is an advisory board and Speakers Bureau member for and has received consulting honoraria from Boston Scientific, Asahi Intecc, and Medtronic. Dr Saghatelyan has received proctoring and speaker honoraria from Asahi Intecc and Terumo. Dr Spaedy is a consultant for Boston Scientific and Abbott Vascular. Dr Stone has received speaker or other honoraria from Cook and Terumo; is a consultant to Valfix, TherOx, Vascular Dynamics, Robocath, HeartFlow, Gore, Ablative Solutions, Miracor, Neovasc, V-Wave, Abiomed, Ancora, MAIA Pharmaceuticals, Vectorious, Reva, Matrizyme, Cardiomech, Elucid Bio, and Occlutech; and holds equity or options with Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, the MedFocus family of funds, and Valfix. Dr Tammam has a proctorship agreement with Terumo. Dr Tremmel has received honoraria from Abbott Vascular and Boston Scientific. Dr Wollmuth has received consulting, speaker, and proctoring honoraria from Abbott Vascular, Abiomed, Asahi Intecc, Biotronik, Boston Scientific, Cardiovascular Systems, Medtronic, and Philips. Dr Ybarra has received consulting and speaker fees from Abbott Vascular Canada and SoundBite Medical Solutions. Dr Yeh has received research grants from Abbott Vascular, AstraZeneca, Cook, BD Bard, Boston Scientific, Medtronic, and Philips; and is a consultant for Abbott Vascular, AstraZeneca, Boston Scientific, Edwards Lifesciences, Medtronic, Shockwave Medical, and Zoll. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Intravascular lithotripsy (IVL) has been shown to be safe and effective for calcium modification in nonocclusive coronary artery disease (CAD), but there are only case reports of its use in calcified chronic total occlusions (CTO). We report data from an international multicenter registry of IVL use during CTO percutaneous coronary intervention (PCI) and provide provisional data regarding its efficacy and safety. During the study period, IVL was used in 55 of 1053 (5.2%) CTO PCI procedures. IVL was used within the occluded segment after successful CTO crossing in 53 procedures and during incomplete CTO crossing in 2 cases. The mean J-CTO score was 3.1. CTO PCI technical and procedural success was achieved in 53 (96%) and 51 (93%) cases. Six patients had a procedural complication, with 3 main vessel perforations (5%). Two had covered stent implantation, one required pericardiocentesis, and one was managed conservatively. All had combination therapy with another calcium modification device. Two patients had a procedural myocardial infarction (PMI) (4%), and two others had a major adverse cardiovascular event (MACE) (4%) at a median follow-up of 13 (4-21) months. IVL can effectively facilitate calcium modification during CTO PCI. More data are required to establish the efficacy and safety of IVL and other calcium modification devices when used extraplaque or in combination during CTO PCI., Competing Interests: AØ has a proctoring agreement with Boston Scientific and EPS Vascular. CC received an educational grant from Shockwave Medical. SW, JS, JS, CH, and MM have consultancy agreement with Boston Scientific, Abbott Vascular, Teleflex, and Shockwave Medical. All other authors have no conflicts of interest., (Copyright © 2021 Anja Øksnes et al.)

Over the past 2 decades, chronic total occlusion (CTO) percutaneous coronary intervention has developed into its own subspecialty of interventional cardiology. Dedicated terminology, techniques, devices, courses, and training programs have enabled progressive advancements. However, only a few randomized trials have been performed to evaluate the safety and efficacy of CTO percutaneous coronary intervention. Moreover, several published observational studies have shown conflicting data. Part of the paucity of clinical data stems from the fact that prior studies have been suboptimally designed and performed. The absence of standardized end points and the discrepancy in definitions also prevent consistency and uniform interpretability of reported results in CTO intervention. To standardize the field, we therefore assembled a broad consortium comprising academicians, practicing physicians, researchers, medical society representatives, and regulators (US Food and Drug Administration) to develop methods, end points, biomarkers, parameters, data, materials, processes, procedures, evaluations, tools, and techniques for CTO interventions. This article summarizes the effort and is organized into 3 sections: key elements and procedural definitions, end point definitions, and clinical trial design principles. The Chronic Total Occlusion Academic Research Consortium is a first step toward improved comparability and interpretability of study results, supplying an increasingly growing body of CTO percutaneous coronary intervention evidence.

Objectives: This study aimed to present a case series of patient treated for stent underexpansion resistant to conventional treatment with intravascular lithotripsy (IVL)., Background: Stent underexpansion is a powerful predictor of long-term stent patency and correlates with unfavorable clinical outcomes. This case series demonstrates the utility of IVL in managing stent underexpansion resistant to conventional treatment., Methods: We describe a case series of patients with stent underexpansion due to calcific coronary artery disease treated with IVL. Stent underexpansion was identified as an inability to adequately expand stents with conventional treatment. Only cases that failed to achieve adequate expansion with high-pressure noncompliant balloon inflation were included., Results: Thirteen patients from six institutions have been included in this case series. The average age was 70.25 years with 76.9% of male patients. The average pre-IVL minimal stent area (MSA) was 2.71 mm 2 , which improved to 6.44 mm 2 post-IVL treatment, representing an average MSA gain of 238%. There were no procedural, peri-procedural, or 30-day major adverse cardiac and cerebrovascular event., Conclusion: This case series demonstrates that IVL is a feasible, safe alternative for the management of stent underexpansion due to calcific coronary disease., (© 2020 Wiley Periodicals, Inc.)

Background: Complex high-risk and indicated revascularization using percutaneous coronary intervention (CHIP-PCI) is an emerging concept that is poorly studied., Objective: To define temporal changes in CHIP-PCI volumes, and the relationship between operator CHIP-PCI volume and patient outcomes., Methods and Results: Data were analyzed on all CHIP-PCI procedures undertaken for stable angina in England and Wales between 2007 and 2014. Operator volume data was available for 2012-14. CHIP-PCI was defined by patient characteristics (age ≥80years, left ventricular (LV) ejection fraction <30%, previous CABG, or chronic renal failure) and/or by procedural characteristics (left main PCI, chronic total occlusion PCI, LV support, use of rotational atherectomy or laser atherectomy). CHIP-PCI as a percentage of total PCI increased from 28.1% in 2007 to 36.2% in 2014 (P < .001). Between 2012 and 2014, a total of 30,268 CHIP-PCI cases were performed. Total operator volume varied from 1 to 580 cases with median total operator volume of 29 cases. Higher operator volumes were associated with a greater degree of patient comorbidity and increasing procedural complexity. After adjustment for baseline difference, in-hospital major bleeding (P < .001 for trend), access site complications (P < .001) and coronary perforation (P = .002) were associated with increasing operator CHIP-PCI volumes. However, the frequency of in-hospital death (P = .394) and 12-month mortality (P = .638) were similar across the volume quartiles. Higher volumes quartiles were associated with a greater likelihood of same day discharge (P < .001)., Conclusions: CHIP-PCI cases are an increasingly large population in contemporary PCI practice. Higher operator volumes were not associated with improved 12-month survival., Condensed Abstract: Data were analyzed on all complex high-risk and indicated revascularization using percutaneous coronary intervention (CHIP-PCI) procedures in England and Wales between 2007 and 2014. CHIP-PCI as a percentage of total PCI increased from 28.1% in 2007 to 36.2% in 2014 (P < .001). Median total operator volume was 29 cases with higher volumes associated with more patient comorbidity and increasing procedural complexity. In-hospital major bleeding (P < .001 for trend), access site complications (P < .001) and coronary perforation (P = .002) all associated with increasing operator CHIP-PCI volumes. However, trends for in-hospital death (P = .394), and 12-month mortality (P = .638) were similar across the volume quartiles., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have improved because of advancements in equipment and techniques. With global collaboration and knowledge sharing, we have identified 7 common principles that are widely accepted as best practices for CTO-PCI.  1. Ischemic symptom improvement is the primary indication for CTO-PCI.  2. Dual coronary angiography and in-depth and structured review of the angiogram (and, if available, coronary computed tomography angiography) are key for planning and safely performing CTO-PCI.  3. Use of a microcatheter is essential for optimal guidewire manipulation and exchanges.  4. Antegrade wiring, antegrade dissection and reentry, and the retrograde approach are all complementary and necessary crossing strategies. Antegrade wiring is the most common initial technique, whereas retrograde and antegrade dissection and reentry are often required for more complex CTOs.  5. If the initially selected crossing strategy fails, efficient change to an alternative crossing technique increases the likelihood of eventual PCI success, shortens procedure time, and lowers radiation and contrast use.  6. Specific CTO-PCI expertise and volume and the availability of specialized equipment will increase the likelihood of crossing success and facilitate prevention and management of complications, such as perforation.  7. Meticulous attention to lesion preparation and stenting technique, often requiring intracoronary imaging, is required to ensure optimum stent expansion and minimize the risk of short- and long-term adverse events. These principles have been widely adopted by experienced CTO-PCI operators and centers currently achieving high success and acceptable complication rates. Outcomes are less optimal at less experienced centers, highlighting the need for broader adoption of the aforementioned 7 guiding principles along with the development of additional simple and safe CTO crossing and revascularization strategies through ongoing research, education, and training.

Aims: To investigate if recent technical and procedural developments in percutaneous coronary intervention (PCI) significantly influence outcomes in appropriately selected patients with three-vessel (3VD) coronary artery disease., Methods and Results: The SYNTAX II study is a multicenter, all-comers, open-label, single arm study that investigated the impact of a contemporary PCI strategy on clinical outcomes in patients with 3VD in 22 centres from four European countries. The SYNTAX-II strategy includes: heart team decision-making utilizing the SYNTAX Score II (a clinical tool combining anatomical and clinical factors), coronary physiology guided revascularisation, implantation of thin strut bioresorbable-polymer drug-eluting stents, intravascular ultrasound (IVUS) guided stent implantation, contemporary chronic total occlusion revascularisation techniques and guideline-directed medical therapy. The rate of major adverse cardiac and cerebrovascular events (MACCE [composite of all-cause death, cerebrovascular event, any myocardial infarction and any revascularisation]) at one year was compared to a predefined PCI cohort from the original SYNTAX-I trial selected on the basis of equipoise 4-year mortality between CABG and PCI. As an exploratory endpoint, comparisons were made with the historical CABG cohort of the original SYNTAX-I trial. Overall 708 patients were screened and discussed within the heart team; 454 patients were deemed appropriate to undergo PCI. At one year, the SYNTAX-II strategy was superior to the equipoise-derived SYNTAX-I PCI cohort (MACCE SYNTAX-II 10.6% vs. SYNTAX-I 17.4%; HR 0.58, 95% CI 0.39-0.85, P = 0.006). This difference was driven by a significant reduction in the incidence of MI (HR 0.27, 95% CI 0.11-0.70, P = 0.007) and revascularisation (HR 0.57, 95% CI 0.37-0.9, P = 0.015). Rates of all-cause death (HR 0.69, 95% CI 0.27-1.73, P = 0.43) and stroke (HR 0.69, 95% CI 0.10-4.89, P = 0.71) were similar. The rate of definite stent thrombosis was significantly lower in SYNTAX-II (HR 0.26, 95% CI 0.07-0.97, P = 0.045)., Conclusion: At one year, clinical outcomes with the SYNTAX-II strategy were associated with improved clinical results compared to the PCI performed in comparable patients from the original SYNTAX-I trial. Longer term follow-up is awaited and a randomized clinical trial with contemporary CABG is warranted., Clinicaltrials.gov Identifier: NCT02015832., (© The Author 2017. Published on behalf of the European Society of Cardiology)

We aimed to determine clinical outcomes 1 year after successful chronic total occlusion (CTO) PCI and, in particular, whether use of dissection and re-entry strategies affects clinical outcomes. Hybrid approaches have increased the procedural success of CTO percutaneous coronary intervention (PCI) but longer-term outcomes are unknown, particularly in relation to dissection and re-entry techniques. Data were collected for consecutive CTO PCIs performed by hybrid-trained operators from 7 United Kingdom (UK) centres between 2012 and 2014. The primary endpoint (death, myocardial infarction, unplanned target vessel revascularization) was measured at 12 months along with angina status. One-year follow up data were available for 96% of successful cases (n = 805). In total, 85% of patients had a CCS angina class of 2-4 prior to CTO PCI. Final successful procedural strategy was antegrade wire escalation 48%; antegrade dissection and re-entry (ADR) 21%; retrograde wire escalation 5%; retrograde dissection and re-entry (RDR) 26%. Overall, 47% of CTOs were recanalized using dissection and re-entry strategies. During a mean follow up of 11.5 ± 3.8 months, the primary endpoint occurred in 8.6% (n = 69) of patients (10.3% (n = 39/375) in DART group and 7.0% (n = 30/430) in wire-based cases). The majority of patients (88%) had no or minimal angina (CCS class 0 or 1). ADR and RDR were used more frequently in more complex cases with greater disease burden, however, the only independent predictor of the primary endpoint was lesion length. CTO PCI in complex lesions using the hybrid approach is safe, effective and has a low one-year adverse event rate. The method used to recanalize arteries was not associated with adverse outcomes. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

The hybrid approach is a systematic algorithm-led percutaneous coronary intervention strategy based on the identification of key anatomical features on coronary angiography to treat chronic total occlusions. The aims of this approach are to provide a standardised tool for physician training and programme development, avoiding futile strategies to improve safety, procedural success and reduce the contrast and radiation required to complete the case., Competing Interests: Disclosure: The authors have no conflicts of interest to declare.

Background: Coronary perforation (CP) during chronic total occlusion percutaneous coronary intervention for stable angina (CTO-PCI) is a rare but serious event. The evidence base is limited, and the long-term effects are unclear. Using a national PCI database, the incidence, predictors, and outcomes of CP during CTO-PCI were defined., Methods and Results: Data analyzed from the British Cardiovascular Intervention Society data set on all CTO-PCI procedures performed in England and Wales between 2006 and 2013. Multivariate logistic regressions and propensity scores were used to identify predictors of CP and its association with outcomes. A total of 376 CP were recorded from 26 807 CTO-PCI interventions (incidence of 1.40%) with an increase in frequency during the study period ( P =0.012). Patient-related factors associated with an increased risk of CP were age and female sex. Procedural factors indicative of complex CTO intervention strongly related to an increased risk of CP with a close relationship between the number of complex strategies used and CP evident ( P =0.008 for trend). Tamponade occurred in 16.6% and emergency surgery in 3.4% of cases. Adverse outcomes were frequent in those patients with perforation including bleeding, transfusion, myocardial infarction, and death. A legacy effect of perforation on mortality was evident, with an odds ratio for 12-month mortality of 1.60 for perforation survivors compared with matched nonperforation survivors without a CP ( P <0.0001)., Conclusions: Many of the factors associated with an increased risk of CP were related to CTO complexity. Perforation was associated with adverse outcomes, with a legacy effect on later mortality after CP also observed., (© 2017 American Heart Association, Inc.)

Gender differences exist in clinical outcomes after routine percutaneous coronary intervention (PCI), but studies reporting such outcomes after chronic total occlusion (CTO) PCI are limited. We assessed the characteristics and outcomes of female patients undergoing CTO PCI. We retrospectively analyzed a dedicated national (United Kingdom) prospective CTO database from 2011 to 2015 for outcomes and characteristics of female patients undergoing CTO PCI (unmatched and propensity matched). Female patients constituted 20.5% (n = 260 of 1,271) of the unmatched cohort and 33.3% (n = 233 of 699) of the matched cohort and were more likely to be older (women aged >70 years, 48% in the unmatched and 45% in the matched cohort). An increased inhospital complication rate was observed in female patients (unmatched: 10% women vs 4.45% men, p = 0.0012, and matched 9.87% women vs 3.86% men, p = 0.0032). Coronary perforation, bleeding, and contrast-induced nephropathy were more frequently observed in female patients. Femoral access site with >6 French sheath was associated with an increased risk of bleeding. Presence of calcification in the CTO artery was associated with coronary perforation (grade III) in female patients in the matched cohort (p = 0.007). Female patients undergoing CTO PCI were older and experienced increased of inhospital complications. Increased awareness of these complications could influence the selection of access site and sheath size, the need for prehydration, judicious choice of balloon size, collateral selection, and wire placement in female patients undergoing CTO PCI., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Objectives: To assess the efficacy and safety of the modified contrast microinjection technique to facilitate chronic total occlusion recanalization., Background: The success rate of chronic total occlusion percutaneous coronary intervention (CTO-PCI) does not exceed 90% even in the most experienced centres. We have previously demonstrated that a large volume of contrast injected into the subintimal space can facilitate recanalization but is limited by a risk of serious complication. The aim of this study was to assess the application, efficacy and safety of a modified contrast microinjection technique that utilizes the injection of a much smaller volume of contrast in CTO-PCI., Methods: A retrospective analysis of patients in whom the modified microinjection technique was utilised in patients undergoing CTO-PCI at five tertiary centres was conducted., Results: Of 1,192 patients who underwent CTO-PCI, the microinjection technique was used in 59 patients (4.7%). The majority of CTOs treated were in the right coronary artery (79.7%), were of high complexity and 35.6% of lesions had a least one previously failed PCI attempt. The modified microinjection technique was used for more than one indication in 7 (11.9%) of patients. The success rate was 81.4%. There were no procedural complications related to the use of the reported modified microinjection., Conclusion: Initial experience with the modified microinjection demonstrates that it can be performed safely, is reproducible, and is broadly applicable. Whilst not required for all CTO procedures it can be a helpful adjunctive tool to increase the likelihood of success especially in complex, or refractory cases, without compromising the safety of the procedure. © 2015 Wiley Periodicals, Inc., (© 2015 Wiley Periodicals, Inc.)

Objectives: The aim of this first-in-human (FIH) study was to evaluate the efficacy and safety of the novel NovaCross microcatheter system in eligible consecutive patients with chronic total occlusion (CTO)., Background: CTOs remain the most challenging lesion subset in percutaneous coronary intervention (PCI). Failure to cross to the distal true lumen with the guidewire is one of the major causes of procedural failure in CTO-PCI. The NovaCross microcatheter (Nitiloop, Ltd) is designed to improve antegrade recanalization success., Methods: This study was a prospective, non-randomized, FIH investigational study. Patients with total occlusion of a coronary artery determined to be more than 3 months old and accepted for coronary CTO-PCI with an intended antegrade strategy were enrolled., Results: Twenty-four patients were enrolled in this study. Despite the high complexity of the lesions (including 80% J-CTO score ≥3 and 50% of the cases having had a previous failed CTO-PCI attempt), technical success was 81.8%. No patients reported any major adverse cardiac event up to and including 30 days post procedure., Conclusion: In this FIH study, the NovaCross microcatheter exhibited the potential to stabilize guidewires and enhance crossing of coronary CTO lesions.

There is substantial evidence that recanalization of a chronic total occlusion is beneficial; nonetheless, it is generally underutilized in clinical practice. We consider the Aesop's fable of the "Fox and the Grapes" as analogous to the current situation in interventional cardiology. The technical challenges in achieving CTO recanalization has led interventionalists, clinical cardiologists, and sometimes even patients to believe that CTO recanalization is not effective, and, therefore, not needed. This perspective reviews available data regarding efficacy and safety of CTO percutaneous coronary intervention (PCI) in the current drug-eluting stent era, discusses areas where more studies are required, and encourages the interventional community to utilize CTO PCI where appropriate based on current evidence., (© 2014 Wiley Periodicals, Inc.)

Objectives: To define the size of the left mainstem coronary artery (LMS) in the Northern Irish population and investigate the clinical feasibility, safety, and efficacy of post dilation beyond nominal diameter of current generation Drug eluting stent (DES) when treating the LMS., Background: There is no prospective data examining the need, feasibility, and safety of over-expansion of current generation DES beyond nominal diameter., Methods: Patients with flow-limiting coronary atheroma requiring IVUS assessment of the LMS were recruited. Standardized measurements of the distal LMS were made. Subsequently, patients requiring post dilation of current generation DES within the LMS were entered into a PCI registry., Results: Overall, 125 patients were recruited into the initial study. Mean cross-sectional area (CSA) of the distal LMS was 22.6 mm(2) (SD ± 5.4 mm(2) ). Mean maximal vessel diameter was 5.7 mm (SD ± 0.7 mm). Increasing plaque burden was associated with reduced CSA (P < 0.001). In 31 consecutive patients undergoing IVUS guided PCI of the LMS with 5.5 and 6.0 mm balloon catheters, mean maximal stent diameters were >5.0 mm with the Biomatrix Flex 9 crown and Promus Element Large vessel platforms. No intraprocedural complications occurred. Mean follow up was 13.4 months. Clinical restenosis rate was 3.2%, with 2 deaths unrelated to index procedure., Conclusions: The majority of patients with angiographic coronary atheroma have a mean LMS diameter of >4 mm indicating the requirement for post dilation beyond nominal diameter all of current generation DES in almost all patients when treating the LMS. This is achievable with current DES platforms with no intraprocedural complication. Clinical follow up indicates excellent short-term efficacy., (© 2013 Wiley Periodicals, Inc.)

Successful revascularisation of chronic total occlusions (CTOs) remains one of the greatest challenges in the era of contemporary percutaneous coronary intervention (PCI). Such lesions are encountered with increasing frequency in current clinical practice. A predictable increase in the future burden of CTO management can be anticipated given the ageing population, increased rates of renal failure, graft failure and diabetes mellitus. Given recent advances and developments in CTO PCI management, successful recanalisation can be anticipated in the majority of procedures undertaken at high-volume centres when performed by expert operators. Despite advances in device technology, the management of resistant, calcific lesions remains one of the greatest challenges in successful CTO intervention. Established techniques to modify calcific lesions include the use of high-pressure non-compliant balloon dilation, cutting-balloons, anchor balloons and high speed rotational atherectomy (HSRA). Novel approaches have proven to be safe and technically feasible where standard approaches have failed. A step-wise progression of strategies is demonstrated, from well-recognised techniques to techniques that should only be considered when standard manoeuvres have proven unsuccessful. These methods will be described in the setting of clinical examples and include use of very high-pressure non-compliant balloon dilation, intentional balloon rupture with vessel dissection or balloon assisted micro-dissection (BAM), excimer coronary laser atherectomy (ECLA) and use of HSRA in various 'offlabel' settings.

In contemporary practice there are three main methods that can be employed when attempting to open a chronic total occlusion (CTO) of a coronary artery; antegrade or retrograde wire escalation, antegrade dissection re-entry and retrograde dissection re-entry. This editorial will attempt to clarify the anatomical features that can be identified to help when deciding which of these strategies to employ initially and help understand the reasons for this decision.

Background: The use of coronary angiography (CA) for diagnosis and management of chest pain (CP) has several flaws. The assessment of coronary artery disease using fractional flow reserve (FFR) is a well-validated technique for describing lesion-level ischemia and improves clinical outcome in the context of percutaneous coronary intervention. The impact of routine FFR at the time of diagnostic CA on patient management has not been determined., Methods and Results: Two hundred patients with stable CP underwent CA for clinical indications. The supervising cardiologist (S.C.) made a management plan based on CA (optimal medical therapy alone, percutaneous coronary intervention, coronary artery bypass grafting, or more information required) and also recorded which stenoses were significant. An interventional cardiologist then measured FFR in all patent coronary arteries of stentable diameter (≥2.25 mm). S.C. was then asked to make a second management plan when FFR results were disclosed. Overall, after disclosure of FFR data, management plan based on CA alone was changed in 26% of patients, and the number and localization of functional stenoses changed in 32%. Specifically, of 72 cases in which optimal medical therapy was recommended after CA, 9 (13%) were actually referred for revascularization with FFR data. By contrast, of 89 cases in whom management plan was optimal medical therapy based on FFR, revascularization would have been recommended in 25 (28%) based on CA., Conclusions: Routine measurement of FFR at CA has important influence both on which coronary arteries have significant stenoses and on patient management. These findings could have important implications for clinical practice., Clinical Trial Registration Url: http://www.clinicaltrial.gov. Unique identifier: NCT01070771.

Aims: Chronic total occlusions (CTO) secondary to in-stent restenosis (ISR) represent challenging lesions with low PCI success rates. The CrossBoss is an over-the-wire blunt catheter which has emerged as a useful tool in occlusive ISR. We aimed to review the utility of this device in the treatment of occlusive ISR within the United Kingdom., Methods and Results: The CrossBoss catheter was used as the primary strategy in 30 patients (31 CTOs) with a median CTO duration of 24 months, a mean CTO length of 39 mm and a previous unsuccessful PCI attempt in 48% of cases. Procedural success was 90% (27/30) and the CrossBoss catheter directly facilitated success in 81% of cases, with direct lumen-to-lumen crossing of the catheter in most cases. Identifiable predictors of failure were evident in the unsuccessful cases. When successful, crossing time was short (median eight minutes, range one to 40 minutes), as were procedural time (mean 99±29 minutes) and fluoroscopy time (mean 26.9±12.2 minutes), whilst radiation dose (median 5,738 cGycm2, range 3,430-64,122 cGycm2) and contrast dose (mean 271±79 mL) were low. There were no procedural complications., Conclusions: In our experience, use of the CrossBoss catheter is associated with high procedural success rates, short crossing times and low complication rates in the setting of occlusive ISR.

Introduction: Rotational atherectomy (RA) is widely used for treating calcified coronary lesions. Clinical data however remain limited., Methods: We assessed outcome and survival among patients undergoing percutaneous coronary intervention (PCI) with or without RA in the UK between September 2007 and March 2011., Results: Data from 221,669 percutaneous coronary intervention (PCI) procedures were analysed; 2152 patients (0.97%) underwent RA (RA+); the remainder underwent conventional PCI (RA-). RA+ patients were older (71.7±9.6 vs. 64.1±12.8 year; p<0.001), and had a higher incidence of diabetes (26.4% vs. 18.0%; p<0.001), hypertension, (61.9% vs. 49.4%; p<0.001), peripheral vascular disease (9.9% vs. 4.2%, p<0.001), cerebrovascular disease (5.5% vs. 3.4%, p<0.001), renal impairment (3.4% vs. 1.5%, p<0.001) and poor left ventricular function (11.4% vs. 4.3%,p<0.001). Procedural success was lower among RA+ patients (90.3% vs 94.6%; p<0.001) and procedural complications were more frequent (9.7% vs 5.4%; p<0.001). After 2.4±1.2 years follow-up, unadjusted Cox proportional hazard modeling demonstrated poorer survival for RA+ patients (HR 2.21, 95%CI 1.97-2.49; p<0.0001). This disadvantage remained after adjustment for adverse variables (HR 1.26, 95%CI 1.11-1.44; p=0.0004) and following propensity analysis. There was evidence however of improved survival for RA+ patients with left main stem disease (HR 0.52, 95%CI 0.35-0.75, p<0.0001), and peripheral vascular disease (HR 0.65, 95%CI 0.43-0.98, p<0.0005)., Conclusions: Rotational atherectomy was undertaken in patients with higher pre-procedural risk. Medium term survival was worse among patients undergoing rotational atherectomy, and this survival disadvantage remained after correction for available adverse factors. Rotational atherectomy however remains clinically useful for patients with calcified coronary lesions., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

A 65-year-old man developed respiratory failure and was admitted to the Intensive Care Unit for positive pressure ventilation and antibiotic and antifungal therapy.There was a sudden deterioration with chest pain, worsening hypoxia and hypotension. Serial electrocardiograms showed new onset right bundle-branch block with developing anterior ST-segment elevation. An urgent coronary angiogram revealed acute occlusion of the left anterior descending artery with a single large distinct thrombus, which was successfully removed with an aspiration catheter. A presumptive diagnosis of paradoxical coronary embolus was made. A short review is provided of this relatively rare clinical entity which has the potential to present in intensive care patients who have an underlying intra-cardiac defect and require positive pressure ventilation. This case emphasises the importance of being aware of less common causes of acute clinical deterioration and electrocardiographic changes in the ventilated patient.

Radial access coronary procedures are associated with fewer access site complications compared to femoral access. There is controversy regarding greater radiation exposure to patient and operator using radial access. We aimed to compare radiation dose during coronary procedures for the 2 access routes and assess the effect of operator experience with radial access on radiation dose. Fluoroscopy time (FT) and dose-area product (DAP) were recorded for all radial access and femoral access procedures during default femoral access, transition phase (femoral access and early radial access), and default radial access. Femoral access cases (n = 848, 412 diagnostic, 436 percutaneous coronary interventions [PCIs]) and radial access cases (n = 965, 459 diagnostic, 506 PCIs) were assessed. For diagnostics, median FT for radial access was longer than for femoral access (4.43 minutes, interquartile range [IQR] 2.55 to 8.18, vs 2.34 minutes, IQR 1.49 to 4.18, p <0.001) and associated with larger DAP (radial access 1,837 μGy·m(2), IQR 1,172 to 2,783, vs femoral access 1,657 μGy·m(2), IQR 1,064 to 2,376, p <0.001). For PCI, FT was longer for radial access (median 12.02 minutes, IQR 7.57 to 17.54, vs femoral access 9.36 minutes, IQR 6.13 to 14.27, p <0.001)-this did not translate into an increased DAP (femoral access median 3,392 μGy·m(2), IQR 2,139 to 5,193, vs radial access 3,682 μGy·m(2), IQR 2,388 to 5,314, p = NS). For diagnostic radial access, FT decreased from the transition phase (n = 134) to the default radial access phase (n = 323, 5.12 minutes, IQR 3.07 to 9.40, vs 4.21 minutes, IQR 2.49 to 7.52, p = 0.03). This was not observed for PCI. In conclusion, transition from femoral access to radial access for diagnostics and PCI increased FT. DAP increased for diagnostic radial access but not PCI compared with femoral access. FTs for radial access diagnostic cases decreased with experience., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Elevated blood levels of Hcy (homocysteine) are associated with endothelial dysfunction in the systemic and coronary arterial beds. We wished to know if similar changes could be detected in the pulmonary circulation, using non-invasive tests. We studied ten normal young men aged 23-31 years, in whom acute hyperhomocysteinaemia was induced by oral ingestion of methionine. Cardiopulmonary exercise testing [including measurement of exhaled breath NO (nitric oxide)] was performed on two occasions, with and without methionine loading. In addition, blood samples for vWf (von Willebrand factor) and factor VIIIc were taken as markers of endothelial function. After oral methionine, plasma Hcy increased from 11.8 +/- 3.1 to 31.2 +/- 10.3 micromol/l (values are means +/- S.D.; P < 0.0001), whereas there was no increase after placebo. After exercise there was an increase in V(NO) (NO production) and circulating plasma levels of vWf and factor VIIIc, but these were similar in the two tests. Exercise time, HR (heart rate) and BP (blood pressure) responses and P V(O2) (peak achieved O2 uptake) were also similar in the two tests. V(E) (expiratory minute ventilation)/ V(CO2) (CO2 production) was similar in the two groups at rest (methionine, 31.9 +/- 3.9; placebo, 30.5 +/- 3.9; P = 0.11), but increased during exercise after methionine (at peak, 32.2 +/- 4.6 compared with 29.9 +/- 2.8; P = 0.016). P(ETCO2) (end-tidal partial pressure of CO2) was also similar in the two groups at rest (35.1 +/- 2.9 compared with 36.8 +/- 3.2; P = 0.11), but decreased throughout the methionine test (peak 34.1 +/- 4.4 compared with 36.7 +/- 3.5; P = 0.006). V(E) vs V(CO2) slope also increased in the methionine test (25.2 +/- 2.4 compared with 22.8 +/- 2.3; P = 0.003). In conclusion, small, but consistent and significant, changes in respiratory gas exchange were seen after methionine loading, compatible with a V / Q (ventilation/perfusion) mismatch due to pulmonary vascular endothelial dysfunction.

The embryological development of the superior vena cava (SVC) is complex. If the left common cardinal vein fails to occlude it can, along with the left duct of Cuvier form a left SVC, which frequently drains into the coronary sinus. This may result in abnormalities in the anatomy of this structure. A persistent left SVC occurs in 0.5% of the normal population, and 3% to 4.3% of patients with congenital heart anomalies. The pacemaking tissue of the heart is derived from two sites near the progenitors of the superior vena cava. The right-sided site forms the sinoatrial node, the left-sided site is normally carried down to an area near the coronary sinus. Out of 300 patients with cardiac rhythm abnormalities, who have undergone electrophysiological studies (EPS), or permanent pacemaker insertion (PPI), we identified 12 patients with cardiac conduction abnormalities and anomalies of venous drainage. Anomalies of the coronary sinus may be associated with abnormalities of the conduction system of the heart. This may be due to the close proximity of the coronary sinus to the final position of the left-sided primitive pacemaking tissue. In our series of 300 patients, 4% had an associated left SVC, a similar incidence to that found in previous studies of congenital heart disease.

Heightened systemic oxidative stress is increasingly recognized as a feature of cystic fibrosis (CF). The consequences of long-term exposure to free radical attack include a predisposition to diseases such as cancer and atherosclerosis. An increased incidence of malignancy among adult patients with CF has been reported, but the absence of atherosclerotic disease is well described. The aim of the present study was to assess endothelial function in vivo and relate this to the potential of serum from patients with CF to induce oxidative-mediated damage in cultured human endothelial cells. A group of 11 CF patients was matched with a group of healthy volunteers with regard to age and sex. Endothelial function was assessed as endothelium-dependent and -independent vasodilation by measuring forearm blood flow in response to infused acetylcholine and sodium nitroprusside respectively. Confluent monolayers of cultured human endothelial cells were exposed to serum from CF patients and control subjects. Following exposure, cell death was assessed by lactate dehydrogenase release, and the degree of lipid peroxidation in the membrane was assessed by measuring the content of lipid hydroperoxides, malondialdehyde and 4-hydroxynonenal. Endothelial monolayers exposed to serum from CF patients released significantly less lactate dehydrogenase following exposure than those exposed to serum from healthy controls (1.8% and 3.0% respectively; mean difference -1.2%; 95% confidence intervals -1.9% to -0.1%; P<0.05) and contained significantly less 4-hydroxynonenal (0.75 and 3.41 micromol/g of protein respectively; mean difference -2.66 micromol/g; 95% confidence intervals -5.10 to -0.22 micromol/g; P<0.05). There was no significant difference between patients and controls in the extent of serum-induced membrane peroxidation, as assessed by malondialdehyde or lipid hydroperoxides, or in endothelial function, as assessed by forearm blood flow. In conclusion, despite evidence for heightened systemic oxidative stress in CF, patients displayed no impairment of endothelial function, and their serum caused significantly less damage to human endothelial cells than that from matched controls.

Traditionally, nitric oxide-mediated alteration in blood vessel tone has been inferred from changes in flow in response to physical and pharmacological interventions using plethysmographic or ultrasonic techniques. We hypothesized that alteration in pulsatile arterial function may represent a more sensitive measure to detect and monitor nitric oxide-mediated modulation of arterial smooth muscle tone. Healthy male volunteers (n = 15) had radial artery pressure pulse waveforms recorded using a calibrated tonometer device. A computer-based assessment of the diastolic pressure decay was employed to quantify changes in arterial waveform morphology in terms of altered pulsatile (arterial compliance) and steady-state (peripheral resistance) haemodynamics. N(G)-nitro-L-arginine methyl ester (L-NAME), a stereospecific inhibitor of nitric oxide synthesis, was infused intravenously in incrementally increasing doses of 0.25, 0.5 and 0.75 mg/kg for 8 min each. Subjects then received either L-arginine or D-arginine (200 mg/kg over 15 min) intravenously in a blinded fashion. On a separate day, subjects had radial artery pressure pulse waveforms recorded before and after the sublingual administration of glyceryl trinitrate, an exogenous donor of nitric oxide. Cardiac output and heart rate decreased and mean arterial blood pressure increased significantly (P < 0.01 for all) in response to the incremental intravenous infusion of L-NAME. Small artery compliance decreased, whereas systemic vascular resistance increased in response to nitric oxide synthesis inhibition (P < 0.01 for both). The intravenous infusion of L-arginine restored the pulsatile and steady-state haemodynamic parameters to pre-treatment values, whereas D-arginine had no effect. Sublingual glyceryl trinitrate decreased systemic vascular resistance by 11%, whereas large artery- and small artery-compliance increased by 25% and 44% respectively. Pressure pulse contour analysis represents a sensitive and convenient technique capable of tracking changes in the pulsatile function of arteries accompanying nitric oxide-mediated alteration in arterial smooth muscle tone.

A mild to moderate elevation of the total homocysteine concentration (tHcy) is now recognized as a risk factor for vascular disease. It is also associated with endothelial dysfunction in middle-aged and elderly individuals without overt atherosclerotic vascular disease. This is important, as endothelial dysfunction is a well recognized early and potentially reversible marker of the atherosclerotic process. We investigated whether mild hyperhomocysteinaemia was associated with endothelial dysfunction in otherwise healthy young males. We compared endothelial function, by measuring forearm blood flow, in 17 males with mild hyperhomocysteinaemia (defined as tHcy >10 micromol/l) and 14 controls with low tHcy (defined as <5 micromol/l). Forearm blood flow was measured in response to the intra-arterial infusion of acetylcholine (endothelial-dependent response) or sodium nitroprusside (endothelial-independent response). Responses to the vasoactive substances were expressed as the area under the curve of the change in forearm blood flow from baseline. Data are given as mean (95% confidence interval). The two groups were well matched for age, body mass index, pulse rate and blood pressure. tHcy was significantly different between the groups [12.3 (10.4-14.2) micromol/l compared with 4.9 (4.6-5.1) micromol/l; P<0.001]. Concentrations of vitamin B(12) and folate were significantly higher in the control group. There was no difference in basal forearm blood flow between the group with mild hyperhomocysteinaemia and the controls, and both the endothelial-dependent [37.5 (26.2-38.8) and 35.3 (26.1-44.4) arbitrary units respectively] and -independent [26.1 (22.2-29.9) and 25.9 (21.0-30.8) units respectively] responses were not significantly different between the groups. Thus the present study demonstrates that, in healthy adults, mild elevation of tHcy was not associated with impaired endothelial-dependent vasodilation. These data suggest an age effect with regard to homocysteine and endothelial dysfunction. The development of vascular disease in individuals with hyperhomocysteinaemia may only result with higher concentrations or after prolonged exposure.

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.