Cardiac Magnetic Resonance–Derived Extracellular Volume Mapping for the Quantification of Hepatic and Splenic Amyloid

BACKGROUND: Systemic amyloidosis is characterized by amyloid deposition that can involve virtually any organ. Splenic and hepatic amyloidosis occurs in certain types, in some patients but not others, and may influence prognosis and treatment. SAP (serum amyloid P component) scintigraphy is uniquely able to identify and quantify amyloid in the liver and spleen, thus informing clinical management, but it is only available in 2 centers globally. The aims of this study were to examine the potential for extracellular volume (ECV) mapping performed during routine cardiac magnetic resonance to: (1) detect amyloid in the liver and spleen and (2) estimate amyloid load in these sites using SAP scintigraphy as the reference standard. METHODS: Five hundred thirty-three patients referred to the National Amyloidosis Centre, London, between 2015 and 2017 with suspected systemic amyloidosis who underwent SAP scintigraphy and cardiac magnetic resonance with T1 mapping were studied. RESULTS: The diagnostic performance of ECV to detect splenic and hepatic amyloidosis was high for both organs (liver: area under the curve, -0.917 [95% CI, 0.880-0.954]; liver ECV cutoff, 0.395; sensitivity, 90.7%; specificity, 77.7%; P<0.001; spleen: area under the curve, -0.944 [95% CI, 0.925-0.964]; spleen ECV cutoff, 0.385; sensitivity, 93.6%; specificity, 87.5%; P<0.001). There was good correlation between liver and spleen ECV and amyloid load assessed by SAP scintigraphy (r=0.504, P<0.001; r=0.693, P<0.001, respectively). There was high interobserver agreement for both the liver and spleen (ECV liver intraclass correlation coefficient, 0.991 [95% CI, 0.984-0.995]; P<0.001; ECV spleen intraclass correlation coefficient, 0.995 [95% CI, 0.991-0.997]; P<0.001) with little bias across a wide range of ECV values. CONCLUSIONS: Our study demonstrates that ECV measurements obtained during routine cardiac magnetic resonance scans in patients with suspected amyloidosis can identify and measure the magnitude of amyloid infiltration in the liver and spleen, providing important clues to amyloid type and offering a noninvasive measure of visceral amyloid burden that can help guide and track treatment

Achieving Optimal Medical Therapy: Insights From the ORBITA Trial

Background: In stable coronary artery disease, medications are used for 2 purposes: cardiovascular risk reduction and symptom improvement. In clinical trials and clinical practice, medication use is often not optimal. The ORBITA (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) trial was the first placebo-controlled trial of percutaneous coronary intervention. A key component of the ORBITA trial design was the inclusion of a medical optimization phase, aimed at ensuring that all patients were treated with guideline-directed truly optimal medical therapy. In this study, we report the medical therapy that was achieved. Methods and Results: After enrollment into the ORBITA trial, all 200 patients entered a 6-week period of intensive medical therapy optimization, with initiation and uptitration of risk reduction and antianginal therapy. At the prerandomization stage, the median number of antianginals established was 3 (interquartile range, 2-4). A total of 195 patients (97.5%) reached the prespecified target of ≥2 antianginals; 136 (68.0%) did not stop any antianginals because of adverse effects, and the median number of antianginals stopped for adverse effects per patient was 0 (interquartile range, 0-1). Amlodipine and bisoprolol were well tolerated (stopped for adverse effects in 4/175 [2.3%] and 9/167 [5.4%], respectively). Ranolazine and ivabradine were also well tolerated (stopped for adverse effects in 1/20 [5.0%] and 1/18 [5.6%], respectively). Isosorbide mononitrate and nicorandil were stopped for adverse effects in 36 of 172 (20.9%) and 32 of 141 (22.7%) of patients, respectively. Statins were well tolerated and taken by 191 of 200 (95.5%) patients. Conclusions: In the 12-week ORBITA trial period, medical therapy was successfully optimized and well tolerated, with few drug adverse effects leading to therapy cessation. Truly optimal medical therapy can be achieved in clinical trials, and translating this into longer-term clinical practice should be a focus of future study. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT02062593

Placebo-controlled efficacy of percutaneous coronary intervention for focal and diffuse patterns of stable coronary artery disease

Background: Physiological assessment with pressure wire pullback can characterize coronary artery disease (CAD) with a focal or diffuse pattern. However, the clinical relevance of this distinction is unknown. We use data from the ORBITA trial (Objective Randomised Blinded Investigation With Optimal Medical Therapy of Angioplasty in Stable Angina) to test if the pattern of CAD predicts the placebo-controlled efficacy of percutaneous coronary intervention (PCI) on stress echocardiography ischemia and symptom end points. Methods: One hundred sixty-four patients in ORBITA underwent blinded instantaneous wave-free ratio (iFR) pullback assessment before randomization. Focal disease was defined as a ≥0.03 iFR unit drop within 15 mm, rather than over a longer distance. Analyses were performed using regression modeling. Results: In the PCI arm (n=85), 48 were focal and 37 were diffuse. In the placebo arm (n=79), 35 were focal and 44 were diffuse. Focal stenoses were associated with significantly lower fractional flow reserve (FFR) and iFR values than diffusely diseased vessels (mean FFR and iFR, focal 0.60±0.15 and 0.65±0.24, diffuse 0.78±0.10 and 0.88±0.08, respectively, P<0.0001). With adjustment for this difference, PCI for focal stenoses resulted in significantly greater reduction in stress echo ischemia than PCI for diffuse disease (P<0.05). The effect of PCI on between-arm pre-randomization adjusted exercise time was 9.32 seconds (95% CI, −17.1 to 35.7 seconds; P=0.487). When stratified for pattern of disease, there was no detectable difference between focal and diffuse CAD (Pinteraction=0.700). PCI improved Seattle Angina Questionnaire angina frequency score and freedom from angina more than placebo (P=0.034; P=0.0035). However, there was no evidence of interaction between the physiological pattern of CAD and these effects (Pinteraction=0.436; Pinteraction=0.908). Conclusions: PCI achieved significantly greater reduction of stress echocardiography ischemia in focal compared with diffuse CAD. However, for symptom end points, no such difference was observed

A Placebo-Controlled Trial of Percutaneous Coronary Intervention for Stable Angina.

Percutaneous coronary intervention (PCI) is frequently performed to reduce the symptoms of stable angina. Whether PCI relieves angina more than a placebo procedure in patients who are not receiving antianginal medication remains unknown. We conducted a double-blind, randomized, placebo-controlled trial of PCI in patients with stable angina. Patients stopped all antianginal medications and underwent a 2-week symptom assessment phase before randomization. Patients were then randomly assigned in a 1:1 ratio to undergo PCI or a placebo procedure and were followed for 12 weeks. The primary end point was the angina symptom score, which was calculated daily on the basis of the number of angina episodes that occurred on a given day, the number of antianginal medications prescribed on that day, and clinical events, including the occurrence of unblinding owing to unacceptable angina or acute coronary syndrome or death. Scores range from 0 to 79, with higher scores indicating worse health status with respect to angina. A total of 301 patients underwent randomization: 151 to the PCI group and 150 to the placebo group. The mean (±SD) age was 64±9 years, and 79% were men. Ischemia was present in one cardiac territory in 242 patients (80%), in two territories in 52 patients (17%), and in three territories in 7 patients (2%). In the target vessels, the median fractional flow reserve was 0.63 (interquartile range, 0.49 to 0.75), and the median instantaneous wave-free ratio was 0.78 (interquartile range, 0.55 to 0.87). At the 12-week follow-up, the mean angina symptom score was 2.9 in the PCI group and 5.6 in the placebo group (odds ratio, 2.21; 95% confidence interval, 1.41 to 3.47; P<0.001). One patient in the placebo group had unacceptable angina leading to unblinding. Acute coronary syndromes occurred in 4 patients in the PCI group and in 6 patients in the placebo group. Among patients with stable angina who were receiving little or no antianginal medication and had objective evidence of ischemia, PCI resulted in a lower angina symptom score than a placebo procedure, indicating a better health status with respect to angina. (Funded by the National Institute for Health and Care Research Imperial Biomedical Research Centre and others; ORBITA-2 ClinicalTrials.gov number, NCT03742050.). [Abstract copyright: Copyright © 2023 Massachusetts Medical Society.

The utility and educational impact of a virtual webinar to deliver an international undergraduate cardiovascular conference

Introduction Conferences are an important avenue for dissemination of knowledge, research and provide networking opportunities for career development. The COVID-19 pandemic has prompted adoption of virtual platforms for delivery of these conferences. The aim of the study was to determine the utility and educational impact of a student-led virtual webinar to deliver an undergraduate cardiovascular conference compared to a traditional in-person conference. Methods We conducted a two-day virtual conference using the Zoom platform in June 2021. The conference consisted of cardiology subspecialty lectures and workshops conducted by a junior doctor, senior cardiology trainees and consultants. The conference also outlaid a virtual poster hall and oral presentation session while networking opportunities were encouraged using breakout rooms and poster hall chat function. A 38-item self-administered online questionnaire was designed and disseminated at the end of the conference to all attending delegates. All data analysis and data visualisation strategies were conducted on R statistical programming. Results Eight-hundred and forty students from 55 countries attended the event. 490 participants (58.5% response rate, 55.9% female) completed the questionnaire. Factors such as weekend conference (84.9%), student-led or organised (84.1%), environmental/sustainable (82.3%), appropriate level for me (81.5%) and comfort to present (80.8%) were deemed to be at least equal to traditional in-person conference. The conference also increased participants’ interest, their core cardiology knowledge and improved their critical analysis and basic echocardiography skills [median 4 (IQR 3-5) for all parameters]. Overall, participants also found it easy to use the virtual platform [median 5 (IQR 5-5)] and easier to ask questions compared to in-person conferences [median 5 (IQR 4-5) vs median 4 (IQR 3-5), p< 0.001]. Conclusion Our virtual conference provided opportunities to students that the COVID-19 pandemic would have otherwise affected, however its utility and educational impact will need to be assessed within its individual context of delivery

Changing student perception of an Online Integrated Structured Clinical Examination during the COVID-19 pandemic

Background: The COVID-19 pandemic has created a hiatus in in-person clinical assessments due to safety and logistical concerns. We aimed to evaluate student perception and utility of an online Integrated Structured Clinical Examinations (ISCEs) during the pandemic. Methods: Final-year medical students from a single institution were offered an online mock ISCE through a student-to-student (“near-peer”) teaching-programme. A questionnaire based cross-sectional study was conducted pre- and post-online mock ISCE. Results: 64 students completed the study. Matched pre- and post-data showed an increase in confidence (p<0.0001), less worry regarding the online format (p<0.0001) and less anxiety about excelling in ISCEs (p<0.001). Students felt that having done the mock, an online format would more positively affect their overall performance (p=0.007). Conclusions: This study demonstrates a positive change in student perception and confidence in online ISCEs. Online ISCEs are thus feasible, though sole reliance on this format may provide an incomplete assessment of student’s overall clinical competency

Cardiopulmonary exercise testing and efficacy of percutaneous coronary intervention: A substudy of the ORBITA trial

Aims Oxygen-pulse morphology and gas exchange analysis measured during cardiopulmonary exercise testing (CPET) has been associated with myocardial ischaemia. We examine the relationship between CPET parameters, myocardial ischaemia and anginal symptoms in patients with chronic coronary syndrome. We also determine the ability of these parameters to predict the placebo-controlled response to percutaneous coronary intervention (PCI). Methods and results Patients with severe single vessel coronary artery disease were randomised 1:1 to PCI or placebo in the ORBITA trial. Subjects underwent pre-randomisation treadmill CPET, dobutamine stress-echocardiography (DSE) and symptom assessment. These assessments were repeated at the end of a 6-week blinded follow-up period. 195 patients with CPET data were randomised (102 PCI, 93 placebo). Patients in whom an oxygen-pulse plateau was observed during CPET had higher (more ischaemic) DSE score (+0.82 segments; 95%CI, 0.40 to 1.25, P=0.0068) and lower FFR (-0.07; -0.12 to -0.02, P=0.011) compared to those without. At lower (more abnormal) oxygen-pulse slopes, there was a larger improvement of the placebo-controlled effect of PCI on DSE score (oxygen-pulse plateau presence [Pinteraction=0.026] and oxygen-pulse gradient [Pinteraction=0.023]) and Seattle angina physical-limitation score (oxygen-pulse plateau presence [Pinteraction=0.037]). Impaired peak VO2, VE/VCO2 slope, peak oxygen-pulse and oxygen-uptake efficacy slope was significantly associated with higher symptom burden but did not relate to severity of ischaemia or predict response to PCI. Conclusion Although selected CPET parameters relate to severity of angina symptoms and quality of life, only an oxygen-pulse plateau detects the severity of myocardial ischaemia and predicts the placebo-controlled efficacy of PCI in patients with single-vessel coronary artery disease

Assessing the publicity and reach of peer-led online medical teaching: A single-event evaluation

Purpose: The COVID-19 pandemic caused significant disruption to higher education, including medical studies. Online learner support became urgently necessary, and peer-support of learning was needed to supplement formal teaching. This study evaluates the impact and delivery media of OSCEazy, a student-led initiative supporting formal teaching across institutional and national boundaries. Methods: A survey was created on Google Forms and disseminated via the Zoom chat function to all the participants at the end of our event titled, “The Cardiology Station”. Results: A large proportion (99.5%) of the students have a Facebook account and (98.7%) use it to keep track of medical events (p=0.45 for comparison). However, a very small proportion of use their other social media to keep up with medical events (p< 0.0001 for comparison). Conclusion: It is evident from our results, that most of our participants used Facebook to keep track of medical events. The use of their other social media platforms (Instagram, etc) to keep track of medical events was limited. Thus, it is important for any organisation, such as ours, who conduct online events to evaluate which platform is most suitable for them to use to publicise their events

Assessing the publicity and reach of peer-led online medical teaching – A single event evaluation

Purpose The Covid-19 pandemic caused significant disruption to Higher Education, including medical studies. Online learner support became urgently necessary, and peer-support of learning was needed to supplement formal teaching. This study evaluates the impact and delivery media of OSCEazy, a student-led initiative supporting formal teaching across institutional and national boundaries. Methods A survey was created on Google Forms and disseminated via the Zoom chat function to all the participants at the end of our event titled, ‘The Cardiology Station.’ Results A large proportion (99.5%) of the students have a Facebook account and (98.7%) use it to keep track of medical events (p=0.45 for comparison). However, a very small proportion of use their other social media to keep up with medical events (p<0.0001 for comparison). Conclusion It is evident from our results, that most of our participants used Facebook to keep track of medical events. The use of their other social media platforms (Instagram, etc) to keep track of medical events was limited. Thus, it is important for any organisation, such as ours, who conduct online events to evaluate which platform is most suitable for them to use to publicise their events