Abstract Background Limited heart rate rise contributes to reduced exercise tolerance for people who have heart failure with reduced ejection fraction (HFrEF), yet rate-adaptive pacing does not improve functional capacity due to an attenuated force-frequency relationship (FFR). How the FFR relates to total peripheral resistance and sympathetic tone in HFrEF is unknown. Methods In a prospective, observational study, participants with HFrEF and controls underwent an incremental pacing protocol, during which heart rate was increased from 50 to 140 beats per minute. At each heart rate increment LV contractility was measured by echocardiography to determine the FFR, as well as continuous beat-to-beat measurement of systolic and diastolic blood pressures with a plethysmography device to determine cardiac output, total peripheral resistance and blood pressure variability (BPV). A microneurography study was then conducted to measure muscle sympathetic nerve activity (MSNA) during incremental pacing. Results A total of 157 participants with HFrEF and 55 controls (mean age 71.1±1.4 years, 172 (81.1%) male) underwent the pacing protocol. We observed single units in seven of 11 participants who participated in the microneurography study. In both groups, LV contractility and cardiac output increased until the peak of the FFR, after which these declined. We observed a reduction in total peripheral resistance, blood pressure variability, MSNA frequency and incidence coinciding with the peak of the FFR, beyond which these increased. Whilst these relationships were present in both groups, they were more evident in participants with HFrEF. Conclusions For people with HFrEF there is a bidirectional relationship between heart rate and sympathetic activation, with a nadir of sympathetic tone occurring at the peak of the FFR. Both excessively low and high heart rates are accompanied by greater sympathetic activation. Taken together, these data suggest that optimal heart rate targets for HFrEF are likely to be individual.

BACKGROUND AND AIMS:Understanding the reasons for, and perceived barriers to, applying for cardiology training is vital to interpret current application trends and address modifiable barriers to entry. A cross-sectional survey was conducted on behalf of the British Junior Cardiologists' Association (BJCA) to assess the opinions of resident doctors interested in pursuing a career in cardiology. METHODS:Data were collected on six domains: demographic information, intention to pursue a career in cardiology, prior clinical and academic experiences, reasons for and perceived barriers to applying for cardiology training (assessed using a Likert scale from one to five), and the impact of the transition from core medical training to internal medicine training. RESULTS:Responses were received from 171 of 307 (56%) eligible BJCA members. Of 171 participants, 109 (63.7%) stated they would definitely, and 29 (17.0%) would probably, apply for cardiology training. Formal research training was limited; of those who had published research, 77 (45.0%) had published fewer than five articles. The primary motivating factor for applying was the opportunity to perform invasive procedures [mean 4.2 ± standard deviation (SD) 1.0]; competition was identified as the most significant barrier, on average (3.8 ± SD 1.2). The transition to internal medicine training was viewed by 111 respondents (64.9%) as primarily serving the purpose of service provision. CONCLUSIONS:These data should allow potential applicants to make an informed decision as to their specialty of choice. Addressing modifiable barriers to entry may encourage a more diverse range of resident doctors to apply for cardiology training.

Background:Pacemakers attempt to accurately mirror normal physiology; however, even normal pacemaker functionality can have undesirable effects. Case Summary:A 59-year-old male with a background including heart failure, presented with symptoms of 'hitting a brick wall' during exertion, years following the implantation of a biventricular pacemaker for third-degree atrioventricular block. He was extensively evaluated, with cardiopulmonary exercise testing and simultaneous device interrogation. After reaching a heart rate of 140 beats/minute, continued exercise resulted in Wenckebach phenomenon and progression to sustained 2:1 atrioventricular block with immediate reductions in oxygen consumption. Ultimately, the aetiology was attributed to upper rate behaviour, rather than the progression of heart failure, and resolved with simple device reprogramming. Discussion:Cardiopulmonary exercise testing is an invaluable tool when evaluating patients who present with cardiovascular symptoms. Device reprogramming is often required, including the use of rate-response algorithms where appropriate. Personalisation is key, with programming tailored to the individual's physiology.

Due to inconclusive evidence, the role and timing of cavity boost radiotherapy (CBRT) following resection of metastases varies in practice globally. Better patient stratification is urgently needed to identify those that might benefit, but limited predictive models exist. This study aims to explore factors associated with improved outcomes in this patient cohort, to inform a clinically useful predictive algorithm. Patients (n=163, M:64, F:99): histologically confirmed brain metastases undergoing resection at a UK Brain Tumour Centre of Excellence from 2016-21. Data collected: primary site, staging, total intracranial metastases, steroid treatment, KPS, surgery, overall survival (OS), local recurrence. Statistical analysis: Restricted Mean Survival Times (RMST), following Inverse Probability of Treatment Weightage (IPTW) confounder adjustment; Univariate and Multivariate Piecewise Cox Proportional Hazards models to identify significant risk factors, with Leave-One-Out Cross-Validation (LOOCV), Likelihood Ratio Test (LRT) and time-dependent Area Under the Curve (AUC) performed as validation. 50 (31%) patients received CBRT (fractionated=31, single-fraction-SRS=19). CBRT demonstrated significant cumulative OS gains from 1 year [RMST: 2.31, 95%CI:-3.30 - -1.40, p=0.002] to 4.6 years [RMST: 6.33, 95%CI:-13.33 - -0.38, p=0.049]. CBRT had the most significant protective effect on OS in the high-risk mortality group (OS<7months) [HR: 0.14, Bootstrapped 95%CI: 0.04-0.39, p=0.0003] compared to moderate-risk (7months45months) groups. Per 10-point increase in postoperative KPS, mortality risk decreased by 19% [HR: 0.98, Bootstrapped 95%CI: 0.97-0.99, p=0.009]. Multivariate modelling was statistically significant overall (LRT χ²=95.5, p<0.0001), with good predictive power (LOOCV C-index: 0.70, 95%CI: 0.64–0.75) across 1-5 years respectively (time-dependent AUCs: 0.711, 0.715, 0.710, 0.638, 0.611). Based on a large, multivariate dataset, with long-term follow-up, we identified postoperative KPS with early, upfront CBRT as being key to conferring significant and sustained benefits to patients. These data informed a risk-adapted predictive model that can be used in the management of this patient cohort.

Vaginal pessaries are widely considered to be a safe and effective non-surgical management option for women with pelvic organ prolapse. Complications may occur, and are more frequent with improper care and certain device designs and materials. It is imperative to provide information to patients about potential complications. We present the case of a woman in her 70s who presented to the Emergency Department with increasing groin and abdominal pain following a vaginal pessary insertion 2 days prior for grade 3 vaginal vault prolapse. On presentation, her abdomen was markedly distended with guarding. Laboratory investigations showed a significant acute kidney injury with a metabolic acidosis. An initial non-contrast CT showed fluid and inflammatory changes surrounding the bladder, and bladder perforation was suspected. A subsequent CT cystogram showed extravasation of contrast from the bladder into the peritoneal cavity, in keeping with an intraperitoneal bladder rupture. The patient underwent an emergency bladder repair in theatre.

BACKGROUND:The Surprise Question, 'Would you be surprised if this person died within the next year?' is a simple tool that can be used by clinicians to identify people within the last year of life. This review aimed to determine the accuracy of this assessment, across different healthcare settings, specialties, follow-up periods and respondents. METHODS:Searches were conducted of Medline, Embase, AMED, PubMed and the Cochrane Central Register of Controlled Trials, from inception until 01 January 2024. Studies were included if they reported original data on the ability of the Surprise Question to predict survival. For each study (including subgroups), sensitivity, specificity, positive and negative predictive values and accuracy were determined. RESULTS:Our dataset comprised 56 distinct cohorts, including 68 829 patients. In a pooled analysis, the sensitivity of the Surprise Question was 0.69 ((0.64 to 0.74) I2=97.2%), specificity 0.69 ((0.63 to 0.74) I2=99.7%), positive predictive value 0.40 ((0.35 to 0.45) I2=99.4%), negative predictive value 0.89 ((0.87 to 0.91) I2=99.7%) and accuracy 0.71 ((0.68 to 0.75) I2=99.3%). The prompt performed best in populations with high event rates, shorter timeframes and when posed to more experienced respondents. CONCLUSIONS:The Surprise Question demonstrated modest accuracy with considerable heterogeneity across the population to which it was applied and to whom it was posed. Prospective studies should test whether the prompt can facilitate timely access to palliative care services, as originally envisioned. PROSPERO REGISTRATION NUMBER:CRD32022298236.

Appendiceal collision tumours are extremely rare, with most reported cases describing tumours consisting of a mucinous component and a neuroendocrine component. Low-grade appendiceal mucinous neoplasms, in some cases, have a tendency to rupture and disseminate their mucin-producing cells throughout the abdominal cavity, leading to a clinical syndrome known as pseudomyxoma peritonei (PMP). We present the case of a 64-year-old male who initially presented with acute appendicitis and was subsequently found to have PMP and appendiceal malignancy. After several years of scans, surgical intervention and histological analysis, it became apparent that the appendiceal malignancy was comprised of distinct cell types. The patient underwent two rounds of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy, which resulted in a 2-year disease-free period. Unfortunately, the PMP recurred, having morphological changes consistent with a more aggressive disease process.

INTRODUCTION:Older patients may be less likely to receive cardiac resynchronisation therapy (CRT) for the management of heart failure. We aimed to describe the differences in clinical response, complications, and subsequent outcomes following CRT implantation compared to younger patients. METHODS:We conducted a retrospective cohort study of unselected, consecutive patients implanted with CRT devices between March 2008 and July 2017. We recorded complications, symptomatic and echocardiographic response, hospitalisation for heart failure, and all-cause mortality comparing patients aged <70, 70-79 and ≥ 80 years. RESULTS:Five hundred and seventy-four patients (median age 76 years [interquartile range 68-81], 73.3% male) received CRT. At baseline, patients aged ≥80 years had worse symptoms, were more likely to have co-morbidities, and less likely to be receiving comprehensive medical therapy, although left ventricular function was similar. Older patients were less likely to receive CRT-defibrillators compared to CRT-pacemakers. Complications were infrequent and not more common in older patients. Age was not a predictor of symptomatic or echocardiographic response to CRT (67.2%, 71.2% and 62.6% responders in patients aged <70, 70-79 and ≥ 80 years, respectively; P = 0.43), and time to first heart failure hospitalisation was similar across age groups (P = 0.28). Ten-year survival was lower for older patients (49.9%, 23.9% and 6.8% in patients aged <70, 70-79 and ≥ 80 years, respectively; P < 0.001). CONCLUSIONS:The benefits of CRT on symptoms and left ventricular function were not different in older patients despite a greater burden of co-morbidities and less optimal medical therapy. These findings support the use of CRT in an ageing population.

Bronchopulmonary sequestration is a rare disease in which a non-functional region of pulmonary tissue receives an aberrant vascular supply and lacks normal communication with the tracheobronchial tree. We present the case of a 30-year-old female with a primary complaint of unexplained weight loss and no other additional signs or symptoms. In view of this, computed tomography imaging was ordered, showing a 33HU mass in the right upper lobe. A specialist radiologist reviewed the images and concluded that the most likely differentials were mediastinal lymphoma or thymic malignancy. Video-assisted thoracoscopic surgery was performed, when it was seen that no malignancy was present, but rather a bronchopulmonary sequestration. Histology confirmed the diagnosis; the patient fared well post-operatively. Bronchopulmonary sequestration is a rare pathology, with most cases occurring in the lower lung lobes. This case is highly atypical, due to the lack of clinical features and the lesion radiologically mimicking the appearance of malignancy.

Metastasis to the supraclavicular lymph nodes usually originate from primary tumours in the head and neck, breast or abdomen. Infradiaphragmatic tumours very rarely metastasise to these nodes. Transitional cell carcinomas (TCCs), also termed urothelial carcinomas, account for ⁓90% of all ureteral cancers; exceptionally few cases have reported such cancers spreading to the supraclavicular fossae. We present the case of a 65-year-old male who was being investigated for gallstones and was subsequently found to have metastatic bony lesions and widespread adenopathy on magnetic resonance cholangiopancreatography. Initially, the primary cancer was an area of contention between clinicians, as radiologists suggested it was of urological origin, but the bladder multidisciplinary team felt the scans did not fulfil this notion. Ultimately, histological analysis confirmed the diagnosis of metastatic TCC.

Situs inversus totalis (SIT) is a rare autosomal recessive anomaly in which the thoracoabdominal viscerae are laterally transposed, introducing unique challenges in surgical scenarios. Only a few reports have demonstrated the treatment of cholecystitis in situs inversus, much less so in the context of portal vascular anomalies. We present the case of a 41-year-old female presenting to the emergency department with right upper quadrant pain, and subsequently found to have left-sided cholecystitis complicated by SIT with portal venous malformations on magnetic resonance cholangiopancreatography and abdominal computed tomography. Initially, she was referred for open cholecystectomy however due to the lack of symptoms and the presence of a tortuous recanalized portal vein presenting multiple thrombotic complications, an expectant approach was adopted. Thus, imaging remains the gold-standard to diagnose SIT and consideration of all congenital risk factors to cholecystectomy is crucial to avoid post-operative complications.

The prevalence, clinical characteristics, management and long-term outcomes of patients with atrial secondary mitral regurgitation (ASMR) are not well described. We performed a retrospective, observational study of consecutive patients with grade III/IV MR determined by transthoracic echocardiography. The aetiology of MR was grouped as being either primary (due to degenerative mitral valve disease), ventricular SMR (VSMR: due to left ventricular dilatation/dysfunction), ASMR (due to LA dilatation), or other. A total of 388 individuals were identified who had grade III/IV MR; of whom 37 (9.5

Objectives Standardised comparison of abdominal muscle and adipose tissue is often utilised in morphometric clinical research. Whilst measurements are traditionally standardised against the patient's height, this may not be always practically feasible. The aim of this study was to investigate the relationship between measurements of the vertebral body and patient height. Methods We analysed cross-sectional CT scans. Measurements of the vertebral body area (VBA), anteroposterior vertebral body diameter (APVBD) and lateral vertebral body diameter (LVBD) were made by two independent investigators by manual tracing. Patients were randomly divided into two groups: Group 1 standar-disation and Group 2 validation. We compared height and vertebral body parameters from patients in Group 1 and mathematically modelled this relationship. We then utilised the model to predict the height of patients in Group 2 and compared this with their actual height. Observer variability was assessed using Bland-Altman plots and t-tests of differences. Results CT scans from 382 patients were analysed. No significant intraobserver or interobserver differences were apparent when measuring vertebral body parameters. We describe models which enable the prediction of the patients' height using the measured VBA, APVBD and LVBD. No significant differences were observed between the patients predicted and actual heights in the validation group. Conclusions We demonstrate an important relationship between measurements of the patient's height and the vertebral body. This can be utilised in future research when the patient's height has not been measured. Advances in knowledge In the absence of the patient's height, we demonstrate that two-dimensional vertebral body parameters may be reliably used to standardise morphometric measurements.