Association between statin therapy dose intensity and radiation cardiotoxicity in non-small cell lung cancer: Results from the NI-HEART study.

INTRODUCTION: Radiation cardiotoxicity is a dose-limiting toxicity and major survivorship issue for patients with non-small cell lung cancer (NSCLC) completing curative-intent radiotherapy, however patients' cardiovascular baseline is not routinely optimised prior to treatment. In this study we examined the impact of statin therapy on overall survival and post-radiotherapy cardiac events. METHODS: Patients treated between 2015-2020 at a regional center were identified. Clinical notes were interrogated for baseline patient, tumor and cardiac details, and both follow-up cancer control and cardiac events. Three cardiologists verified cardiac events. Radiotherapy planning scans were retrieved for application of validated deep learning-based autosegmentation. Pre-specified Cox regression analyses were generated with varying degrees of adjustment for overall survival. Fine and Gray regression for the risk of cardiac events, accounting for the competing risk of death and cardiac covariables was undertaken. RESULTS: Statin therapy was prescribed to 59% of the 478 included patients. The majority (88%) of patients not prescribed a statin had at least one indication for statin therapy according to cardiovascular guidelines. In total, 340 patients (71%) died and 79 patients (17%) experienced a cardiac event. High-intensity (HR 0.68, 95%CI 0.50-0.91, p = 0.012) and medium-intensity (HR 0.70, 95%CI 0.51-0.97, p = 0.033) statin therapy were associated with improved overall survival after adjustment for patient, cancer, treatment, response and cardiovascular clinical factors. There were no consistent differences in the rate or grade of cardiac events according to statin intensity. CONCLUSIONS: Statin therapy is associated with improved overall survival in patients receiving curative-intent radiotherapy for NSCLC, and there is evidence of a dose-response relationship. This study highlights the importance of a pre-treatment cardiovascular risk assessment in this cohort. Further studies are needed to examine if statin therapy is cardioprotective in patients undergoing treatment for NSCLC with considerable incidental cardiac radiation dose and a low baseline cardiac risk.

Sex-based difference in fractional flow reserve and its impact on clinical outcomes.

BACKGROUND: Obesity is a real public health problem and is of growing concern. People are resorting to surgical or endoscopic means to fight against overweight and obesity. In recent years, there has been a marked increase in the use of these means and in particular the insertion of a gastric balloon which seems to present less risk than surgical methods. Renal complications from intragastric balloon placement are extremely rare. We report here the case of compression of the left renal vein revealed by lumbar pain and hematuria in an overweight 39-year-old woman who benefited from the balloon gastric placement one month before symptoms. The scanner made the diagnosis and showed a good evolution after the withdrawal of the balloon. METHODS: This was a prespecified and retrospective analysis of all consecutive patients who underwent FFR assessment for intermediate coronary lesions between January 2014 and December 2015. The primary endpoint was defined as the 1-year composite of cardiac death, vessel-related myocardial infarction, and clinically-driven target vessel revascularization. RESULTS: In 1554 lesions (23% in women), FFR was lower in men [0.83 ±0.09 vs 0.85 ±0.08, P = .004] driven by LAD values (for LAD P < .001, LCx or RCA P> .40). In proximal lesions (PLs), FFR was lower in men [0.83 ±0.10 vs 0.85 ±0.08, P = .004] with comparable values in non-PLs [0.84 ±0.09 vs 0.85 ±0.08, P = .36]. In PLs, the primary endpoint was higher in women [HR(adjusted) 3.18 (1.08-9.37), P = .035] with comparable outcomes in non-PLs (P = .032 for interaction). In deferred lesions, the primary endpoint was higher in women [HR(adjusted) 2.73 (1.10-6.74), P = .03] with no differences in revascularized lesions across sex (P = .02 for interaction). Results were consistent when using propensity score matching analysis. CONCLUSIONS: There is a sex-based difference in FFR, particularly in stenoses subtending large myocardium, and more evident in deferred lesions.

Comparative Analysis of the Effect of Renal Function on the Spectrum of Coronary Artery Disease.

BACKGROUND: We aim to assess the differential effect of renal impairment across the spectrum of patients with ischaemic heart disease and to study if any established risk factors may modify this risk. METHODS: A total of 2013 patients who underwent revascularization for ST-segment elevation myocardial infarction or invasive physiology assessment were included. Renal impairment was defined as glomerular filtration rate less than 60 ml/min/1.73m2. Clinical endpoints were prospectively collected, and the primary endpoint was defined as the composite endpoints of death, myocardial infarction, and unplanned revascularization. RESULTS: 593 (30%) presented with ST-segment elevation myocardial infarction, and 1362 (70%) stable patients had invasive ischaemia assessment which resulted in 37% receiving revascularization and 63% being deferred. Renal impairment was associated with increased adverse events in myocardial infarction [HR 1.77 (95% CI 1.15 to 2.74)], but not in the revascularized stable group [(HR 1.14 (95% CI 0.62 to 2.08)] or the deferred group [HR 1.31 (95% CI 0.84 to 2.03)]. There was an exponential increase in the future risk in ST-segment elevation myocardial infarction patients with severe renal dysfunction (glomerular filtration rate < 30) compared to a linear relationship in stable patients. Age and hypertension were the only two factors that had a differential impact across three groups (P<0.05 for interactions), with inconsistent directional effect of hypertension between medically managed and revascularized groups. CONCLUSIONS: The magnitude of risk of renal impairment varies according to the clinical presentation of coronary artery disease with more weighted risk in myocardial infarction compared to stable patients.

Clinical Outcomes of Deferred Revascularisation Using Fractional Flow Reserve in Diabetic Patients.

BACKGROUND: Fractional flow reserve (FFR) is used to assess the functional significance of coronary artery lesions. Diabetic patients are associated with high burden of atherosclerosis and microvascular dysfunction. We studied the clinical outcomes of diabetic patients who underwent FFR-guided deferred revascularisation. METHODS: Consecutive patients from a single large volume centre who underwent FFR assessment were included. Clinical endpoints were prospectively collected using the national electronic care records system. The primary endpoint was defined as the four-year risk of the vessel-oriented composite outcome of cardiac death, vessel-related myocardial infarction (VMI), and vessel-related urgent revascularisation (VUR). Absolute FFR values groups (0.81 to 0.85; 0.86 to 0.90; and >0.90) were used to further stratify patient outcomes. RESULTS: FFR-guided deferred revascularisation occurred in 860 patients (63%), of whom 159 were diabetic. The primary endpoint was significantly higher in the diabetic compared to the non-diabetic group [HR 1.76 (95%CI 1.08 to 2.88), P = 0.024]. The difference was driven from cardiac death (6.3% vs. 3.0%, P = 0.044) and VMI (5.0% vs. 1.7%, P = 0.012) but not VUR (8.8% vs. 5.1%, P = 0.07). There was a significant decrease in the incidence of the primary endpoint in the diabetic group according to FFR groups (23.6%, 12.3%, 2.4%, P = 0.001) with comparable clinical outcomes in the non-diabetic group (11.8%, 6.4%, 7.4%, P = 0.085). CONCLUSIONS: Our study demonstrated an increased risk of death and target vessel MI in diabetic patients undergoing FFR-guided deferred revascularisation compared to non-diabetic group. Nonetheless, FFR remained a useful tool to identify those at future risk, mainly in diabetic patients.

The evolution of coronary stents.

INTRODUCTION: Percutaneous coronary intervention (PCI) is 40 years old this year. From its humble beginnings of experimental work, PCI has transitioned over years with coronary artery stenting now a standard medical procedure performed throughout the world. Areas covered: The conversion from plain old balloon angioplasty (POBA) to the present era of drug eluting stents (DES) has been driven by many technological advances and large bodies of clinical trial evidence. The journey to present day practice has seen many setbacks, such as acute vessel closure with POBA; rates of instant restenosis with bare metal stents (BMS) and more recently, high rates of stent thrombosis with bioabsorbable platforms. This work discusses POBA, why there was a need for BMS, the use of inhibiting drugs to create 1st generation DES, the change of components to 2nd generation DES, the use of absorbable drug reservoirs and platforms, and possible future directions with Prohealing Endothelial Progenitor Cell Capture Stents. Expert commentary: This paper reviews the evolution from the original pioneering work to modern day practice, highlighting landmark trials that changed practice. Modern day contemporary practice is now very safe based on the latest drug eluting stents and supported by large datasets.

Management and Prevention of Saphenous Vein Graft Failure: A Review.

Coronary artery bypass grafting (CABG) remains a vital treatment for patients with multivessel coronary artery disease (CAD), especially diabetics. The long-term benefit of the internal thoracic artery graft is well established and remains the gold standard for revascularization of severe CAD. It is not always possible to achieve complete revascularization through arterial grafts, necessitating the use of saphenous vein grafts (SVG). Unfortunately, SVGs do not have the same longevity, and their failure is associated with significant adverse cardiac outcomes and mortality. This paper reviews the pathogenesis of SVG failure, highlighting the difference between early, intermediate, and late failure. It also addresses the different surgical techniques that affect the incidence of SVG failure, as well as the medical and percutaneous prevention and treatment options in contemporary practice.

A Review of the Key Clinical Trials of 2015: Results and Implications.

INTRODUCTION: Multiple significant, potentially practice changing clinical trials in cardiology have been conducted and subsequently presented throughout the past year. METHODS: In this paper, the authors have reviewed and contextualized significant cardiovascular clinical trials presented at major international conferences of 2015 including American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, American Diabetes Association, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Rhythm Congress, and the American Heart Association Scientific Sessions. RESULTS: The authors describe new trial data for heart failure (including eplerenone, finerenone, patiromer, sacubitril/valsartan, the beta 3 agonist mirabegron, sitagliptin, empagliflozin, alginate-hydrogel LV epicardial implant), anticoagulation (idarucizumab and andexanet alfa reversal agents, adherence programmes, practice in ablation), transcatheter aortic valve replacement (long-term data, valve-in-valve use, the TriGuard embolic deflecting device), patent foramen ovale closure, cardiovascular prevention (PCSK9 inhibitors, hypertension treatment) and antiplatelets strategies (extended duration therapy with clopidogrel or ticagrelor). Trial data are also described for contemporary technologies including the Biofreedom polymer-free drug coated stent, bioabsorbable stents, PCI strategies, left main treatment, atrial fibrillation ablation techniques, leadless pacemakers and the role of coronary computed tomographic angiography. CONCLUSIONS: This paper summarizes and contextualizes multiple pertinent 2015 clinical trials and will be of interest to both clinicians and cardiology researchers.

Serum- and HDL3-serum amyloid A and HDL3-LCAT activity are influenced by increased CVD-burden.

BACKGROUND: High density lipoproteins (HDL) protect against cardiovascular disease (CVD). However, increased serum amyloid-A (SAA) related inflammation may negate this property. This study investigated if SAA was related to CVD-burden. METHODS: Subjects referred to the rapid chest pain clinic (n = 240) had atherosclerotic burden assessed by cardiac computerised tomography angiography. Subjects were classified as: no-CVD (n = 106), non-obstructive-CVD, stenosis<50% (n = 58) or moderate/significant-CVD, stenosis ≥50% (n = 76). HDL was subfractionated into HDL2 and HDL3 by rapid-ultracentrifugation. SAA-concentration was measured by ELISA and lecithin cholesterol acyltransferase (LCAT) activity measured by a fluorimetric assay. RESULTS: We illustrated that serum-SAA and HDL3-SAA-concentration were higher and HDL3-LCAT-activity lower in the moderate/significant-CVD-group, compared to the no-CVD and non-obstructive-CVD-groups (percent differences: serum-SAA, +33% & +30%: HDL3-SAA, +65% and +39%: HDL3-LCAT, -6% & -3%; p < 0.05 for all comparisons). We also identified a positive correlation between serum-SAA and HDL3-SAA (r = 0.698; p < 0.001) and a negative correlation between HDL3-SAA and HDL3-LCAT-activity (r = -0.295; p = 0.003), while CVD-burden positively correlated with serum-SAA (r = 0.150; p < 0.05) and HDL3-SAA (r = 0.252; p < 0.001) and negatively correlated with HDL3-LCAT-activity (r = -0.182; p = 0.006). Additionally, multivariate regression analysis adjusted for age, gender, CRP and serum-SAA illustrated that HDL3-SAA was significantly associated with modifying CVD-risk of moderate/significant CVD-risk (p < 0.05). CONCLUSION: This study has demonstrated increased SAA-related inflammation in subjects with moderate/significant CVD-burden, which appeared to impact on the antiatherogenic potential of HDL. We suggest that SAA may be a useful biomarker to illustrate increased CVD-burden, although this requires further investigation.

Reperfusion Options for ST Elevation Myocardial Infarction Patients with Expected Delays to Percutaneous Coronary Intervention.

Primary percutaneous coronary intervention (PCI) is the preferred reperfusion strategy for ST elevation myocardial infarction (STEMI). However, only one-third of hospitals in the US have PCI availability 24/7. For non-PCI hospitals, transfer remains the optimal strategy. For expected delays of greater than 120 minutes, a pharmacoinvasive strategy is recommended. In patients with evidence of failed reperfusion or hemodynamic instability, immediate rescue PCI should be performed. All other patients should undergo routine cardiac catheterization and PCI within 24 hours after fibrinolysis. A pharmacoinvasive strategy is best implemented within an organized regional STEMI system with prospective standardized transfer protocols.

The Essentials of Cardiac Computerized Tomography.

Cardiac computerized tomography (CT) has evolved from a research tool to an important diagnostic investigation in cardiology, and is now recommended in European, US, and UK guidelines. This review is designed to give the reader an overview of the current state of cardiac CT. The role of cardiac CT is multifaceted, and includes risk stratification, disease detection, coronary plaque quantification, defining congenital heart disease, planning for structural intervention, and, more recently, assessment of ischemia. This paper addresses basic principles as well as newer evidence.

A Review of Current Diagnosis, Investigation, and Management of Acute Coronary Syndromes in Elderly Patients.

The elderly constitute a sizeable proportion of the acute coronary syndrome (ACS) population, and this population is continually increasing in number. Guideline-directed therapy is frequently underutilized in the elderly due to concerns about patient safety. However, studies suggest that this subgroup could benefit from many of the conventional and newer therapies available. This paper reviews current literature in the context of contemporary American and European guidance.

A Review of the Key Clinical Trials of 2014.

INTRODUCTION: Over the last year, multiple, potentially practice-changing, cardiology trials or studies have been published or presented at international meetings including the American College of Cardiology, European Association for Percutaneous Cardiovascular Interventions, European Society of Cardiology, Transcatheter Cardiovascular Therapeutics, Heart Failure Congress, Heart Rhythm Society, Heart Failure Society of America, American Society of Hypertension and the American Heart Association. METHODS: Clinical trial results presented at major cardiology conferences during 2014 were reviewed by the authors. Search terms included heart failure (HF), acute coronary syndrome, stable coronary disease, interventional cardiology, atrial fibrillation, electrophysiology and coronary prevention. Selection criteria were trials of broad relevance to the cardiology community, those with potential to change current practice and those with potential to guide further phase III research. RESULTS: In this paper, the authors describe and place in clinical context, new HF, data including neprilysin inhibitors, intravenous ferric carboxymaltose, potassium-absorbing compounds, quadripolar leads for cardiac resynchronization therapy and intraventricular device intervention. New trial data are also described for acute coronary syndromes (clopidogrel, prasugrel, ticagrelor), stable coronary artery disease (ivabradine), percutaneous coronary intervention (the role of thrombectomy or treatment of non-culprit lesions during primary intervention, pressure wire studies and outcomes of new stent designs), transcatheter aortic valve intervention data, atrial fibrillation (anticoagulation and direct current cardioversion), electrophysiology (leadless pacemaker devices, use of quinidine in Brugada syndrome) and coronary prevention (landmark Ezetimibe outcome data, PCSK9 clinical trials, childhood prevalence of hypertension, renal denervation for resistant hypertension and the role of cardiac computerized tomography in cardiovascular screening). CONCLUSION: This paper summarizes key clinical trials during 2014 and should be of practical interest to clinicians and cardiology researchers.

Addressing discrepancies: personal experience of a cardiac mission programme in Africa.

The worldwide incidence of cardiovascular disease (CVD) is increasing, reflecting a combination of ongoing infective diseases and a rapid rise in traditional 'western' risk factors. It is estimated that in the next 20 years that CVD be the leading cause of death in developing nations. There are high incidences of rheumatic heart disease, coronary artery disease, cardiomyopathies, uncorrected congenital heart disease and human immunodeficiency virus (HIV) associated disease in many low-income countries. Such high levels combined with a lack of diagnostic tests and therapeutic options means mortality and morbidity rates are high. A number of charities and organizations have tried to address the discrepancy of cardiac care within developing areas although the needs remain great. However there is no one global cardiac organization that coordinates such humanitarian work. The challenges of missionary work include the need for appropriate facilities, financial constraints of clinical consumables, and lack of education of local healthcare staff, making the move away from the mission model difficult. The strategy for delivery of care in developing countries should be long term educational and technical support, so that local case volumes increase. However it must be realized that there are many different levels of local services within developing nations with different health and educational needs, including some countries with very high facilities and skills levels, yet high case loads. This paper highlights the personal experience of our organization and the types of diseases encountered in developing countries.

A comparison of Diamond Forrester and coronary calcium scores as gatekeepers for investigations of stable chest pain.

To determine if calcium scores (CS) could act as a more effective gatekeeper than Diamond Forrester (DF) in the assessment of patients with suspected coronary artery disease (CAD). A sub-study of the Cardiac CT for the Assessment of Chest Pain and Plaque (CAPP) study, a randomised control trial evaluating the cost-effectiveness of cardiac CT in symptomatic patients with stable chest pain. Stable pain was defined as troponin negative pain without symptoms of unstable angina. 250 patients undergoing cardiac CT had both DF scores and CS calculated, with the accuracy of both evaluated against CT coronary angiogram. Criteria given in UK national guidelines were compared. Of the 250 patients, 4 withdrew. 140 (57 %) patients were male. The mean DF was 47.8 and mean CS 172.5. Of the 144 patients with non-anginal pain 19.4 % had significant disease (>50 % stenosis). In general the DF over estimated the presence of CAD whereas the CS reclassified patients to lower risk groups, with 91 in the high risk DF category compared to 26 in the CS. Both receiver operating curve and McNemar Bowker test analysis suggested the DF was less accurate in the prediction of CAD compared to CS [Formula: see text] Projected downstream investigations were also calculated, with the cost per number of significant stenoses identified cheaper with the CS criteria. Patients with suspected stable CAD are more accurately risk stratified by CS compared to the traditional DF. CS was more successful in the prediction of significant stenosis and appears to be more effective at targeting clinical resources to those patients that are in need of them.

Evaluation of a final year work-shadowing attachment.

The transition from medical student to junior doctor is well recognised to be a difficult and stressful period. To ease this transition, most UK universities have a work-shadowing period (WSP), during which students can learn practical skills needed for forthcoming employment. The aim of this study was to evaluate the WSP at Queen's University Belfast, and gain the views of both students and Foundation Programme Supervisors and Directors (FPSDs). The study utilised both qualitative (focus groups) and quantitative (questionnaires) approaches. The FPSDs completed a specific questionnaire designed for this study, while the students completed the university's internal quality assurance questionnaire. Twenty-eight of the 37 (76%) FPSDs and 106 / 196 (54%) students completed the questionnaires. Focus groups were conducted with up to 10 students in each group in both a regional centre and a district general hospital at the start and the end of the WSP as well as 8 weeks into working life. The transcripts of the focus groups were analysed and themes identified. A number of deficiencies with the current WSP were identified, including concerns about the use of log books, the timing of the attachment and relatively low levels of supervision provided by senior hospital staff members. As a result, students felt unprepared for commencing work, with particular mention given to medical emergencies, prescribing, and the emotional aspects of the job. A number of recommendations are made, including the need for more senior input to ensure better student attendance, participation and clinical interaction. Furthermore, students should be offered additional supervised responsibility for delivery of patient care and more experiential learning with respect to drug prescribing and administration. The study also suggests that more needs to be done to help ease the emotional and psychological stresses of the early FY1 period. These issues have been resolved to a large extent with the introduction of the new final year Student Assistantship module in the academic year 2010-2011.

Delayed cardiac perforation by defibrillator lead placed in the right ventricular outflow tract resulting in massive pericardial effusion.

A 76-year-old man received a dual-chamber implantable cardioverter defibrillator (ICD), with the defibrillator lead positioned within the right ventricular outflow tract. The lead parameters at the time of implantation were satisfactory and the post-procedure chest X-ray showed the leads were in place. The patient was cardioverted from atrial fibrillation during defibrillation threshold testing and commenced on anticoagulation immediately. One month post implantation, he experienced multiple ventricular tachycardia episodes all successfully treated with antitachycardia pacing and shocks by his ICD, but he fell and hit his chest against a hard surface during one of these attacks. He developed a massive pericardial effusion and computed tomography confirmed cardiac perforation by the defibrillator lead. Pericardiocentesis was performed and the defibrillator lead replaced with a different model positioned at the right ventricular apex. The patient made an uneventful recovery. The management and avoidance of delayed cardiac perforation by transvenous leads were discussed.