Cardio-oncology in advanced prostate cancer.

Treatment intensification with androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPi) have led to improved survival in advanced prostate cancer. However, ADT is linked to significant cardiovascular toxicity, and ARPi also negatively impacts cardiovascular health. Together with a higher prevalence of baseline cardiovascular risk factors reported among prostate cancer survivors at diagnosis, there is a pressing need to prioritise and optimise cardiovascular health in this population. Firstly, While no dedicated cardiovascular toxicity risk calculators are available, other tools such as SCORE2 can be used for baseline cardiovascular risk assessment. Next, selected patients on combination therapy may benefit from de-escalation of ADT to minimise its toxicities while maintaining cancer control. These patients can be characterised by an exceptional PSA response to hormonal treatment, favourable disease characteristics and competing comorbidities that warrant a less aggressive treatment regime. In addition, emerging molecular and genomic biomarkers hold the potential to identify patients who are suited for a de-escalated treatment approach either with ADT or with ARPi. One such biomarker is AR-V7 splice variant that predicts resistance to ARPi. Lastly, optimization of modifiable cardiovascular risk factors for patients through a coherent framework (ABCDE) and exercise therapy is equally important. This article aims to comprehensively review the cardiovascular impact of hormonal manipulation in metastatic hormone-sensitive prostate cancer, propose overarching strategies to mitigate cardiovascular toxicity associated with hormonal treatment, and, most importantly, raise awareness about the detrimental cardiovascular effects inherent in our current management strategies involving hormonal agents.

Point-of-care AI-enhanced novice echocardiography for screening heart failure (PANES-HF).

The increasing prevalence of heart failure (HF) in ageing populations drives demand for echocardiography (echo). There is a worldwide shortage of trained sonographers and long waiting times for expert echo. We hypothesised that artificial intelligence (AI)-enhanced point-of-care echo can enable HF screening by novices. The primary endpoint was the accuracy of AI-enhanced novice pathway in detecting reduced LV ejection fraction (LVEF) < 50%. Symptomatic patients with suspected HF (N = 100, mean age 61 ± 15 years, 56% men) were prospectively recruited. Novices with no prior echo experience underwent 2-weeks' training to acquire echo images with AI guidance using the EchoNous Kosmos handheld echo, with AI-automated reporting by Us2.ai (AI-enhanced novice pathway). All patients also had standard echo by trained sonographers interpreted by cardiologists (reference standard). LVEF < 50% by reference standard was present in 27 patients. AI-enhanced novice pathway yielded interpretable results in 96 patients and took a mean of 12 min 51 s per study. The area under the curve (AUC) of the AI novice pathway was 0.880 (95% CI 0.802, 0.958). The sensitivity, specificity, positive predictive and negative predictive values of the AI-enhanced novice pathway in detecting LVEF < 50% were 84.6%, 91.4%, 78.5% and 94.1% respectively. The median absolute deviation of the AI-novice pathway LVEF from the reference standard LVEF was 6.03%. AI-enhanced novice pathway holds potential to task shift echo beyond tertiary centres and improve the HF diagnostic workflow.

Water Conservation Overrides Osmotic Diuresis During SGLT2 Inhibition in Patients With Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors are believed to improve cardiac outcomes due to their osmotic diuretic potential. OBJECTIVES: The goal of this study was to test the hypothesis that vasopressin-driven urine concentration overrides the osmotic diuretic effect of glucosuria induced by dapagliflozin treatment. METHODS: DAPA-Shuttle1 (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment) was a single-center, double-blind, randomized, placebo-controlled trial, in which patients with chronic heart failure NYHA functional classes I/II and reduced ejection fraction were randomly assigned to receive dapagliflozin 10 mg daily or placebo (1:1) for 4 weeks. The primary endpoint was change from baseline in urine osmolyte concentration. Secondary endpoints included changes in copeptin levels and solute free water clearance. RESULTS: Thirty-three randomized, sodium-glucose cotransporter 2 inhibitor-naïve participants completed the study, 29 of whom (placebo: n = 14; dapagliflozin: n = 15) provided accurate 24-hour urine collections (mean age 59 ± 14 years; left ventricular ejection fraction 31% ± 9%). Dapagliflozin treatment led to an isolated increase in urine glucose excretion by 3.3 mmol/kg/d (95% CI: 2.51-4.04; P < 0.0001) within 48 hours (early) which persisted after 4 weeks (late; 2.7 mmol/kg/d [95% CI: 1.98-3.51]; P < 0.0001). Dapagliflozin treatment increased serum copeptin early (5.5 pmol/L [95% CI: 0.45-10.5]; P < 0.05) and late (7.8 pmol/L [95% CI: 2.77-12.81]; P < 0.01), leading to proportional reductions in free water clearance (early: -9.1 mL/kg/d [95% CI: -14 to -4.12; P < 0.001]; late: -11.0 mL/kg/d [95% CI: -15.94 to -6.07; P < 0.0001]) and elevated urine concentrations (late: 134 mmol/L [95% CI: 39.28-229.12]; P < 0.01). Therefore, urine volume did not significantly increase with dapagliflozin (mean difference early: 2.8 mL/kg/d [95% CI: -1.97 to 7.48; P = 0.25]; mean difference late: 0.9 mL/kg/d [95% CI: -3.83 to 5.62]; P = 0.70). CONCLUSIONS: Physiological-adaptive water conservation eliminated the expected osmotic diuretic potential of dapagliflozin and thereby prevented a glucose-driven increase in urine volume of approximately 10 mL/kg/d · 75 kg = 750 mL/kg/d. (Hepato-renal Regulation of Water Conservation in Heart Failure Patients With SGLT-2 Inhibitor Treatment [DAPA-Shuttle1]; NCT04080518).

Cardiovascular disease risk assessment and multidisciplinary care in prostate cancer treatment with ADT: recommendations from the APMA PCCV expert network.

PURPOSE: Androgen deprivation therapy (ADT) is the mainstay approach for prostate cancer (PCa) management. However, the most commonly used ADT modality, gonadotropin-releasing hormone (GnRH) agonists, has been associated with an increased risk of cardiovascular disease (CVD). METHODS: The PCa Cardiovascular (PCCV) Expert Network, consisting of multinational urologists, cardiologists and oncologists with expertise in managing PCa, convened to discuss challenges to routine cardiovascular risk assessment in PCa management, as well as how to mitigate such risks in the current treatment landscape. RESULTS: The experts identified several barriers, including lack of awareness, time constraints, challenges in implementing risk assessment tools and difficulties in establishing multidisciplinary teams that include cardiologists. The experts subsequently provided practical recommendations to improve cardio-oncology care for patients with PCa receiving ADT, such as simplifying cardiovascular risk assessment, individualising treatment based on CVD risk categories, establishing multidisciplinary teams and referral networks and fostering active patient engagement. A streamlined cardiovascular risk-stratification tool and a referral/management guide were developed for seamless integration into urologists' practices and presented herein. The PCCV Expert Network agreed that currently available evidence indicates that GnRH antagonists are associated with a lower risk of CVD than that of GnRH agonists and that GnRH antagonists are preferred for patients with PCa and a high CVD risk. CONCLUSION: In summary, this article provides insights and guidance to improve management for patients with PCa undergoing ADT.

Approaches to Prevent and Manage Cardiovascular Disease in Patients Receiving Therapy for Prostate Cancer.

PURPOSE OF REVIEW: Prostate cancer (PCa) is amongst the most common cancers in men worldwide. Cardiovascular (CV) risk factors and CV disease (CVD) are common comorbidities in this patient population, posing a challenge for PCa-directed therapies which can cause or worsen CVRFs and CVDs. Herein, we summarize the approaches to prevent and manage CVD in patients with PCa receiving therapy. RECENT FINDINGS: While patients with locally advanced and metastatic PCa benefit from hormonal therapy, these treatments can potentially cause CV toxicity. Androgen receptor targeting therapies, such as androgen deprivation therapy (ADT), can induce metabolic changes and directly impact cardiovascular function, thereby reducing cardiorespiratory fitness and increasing CV mortality. Moreover, more than half of the PCa patients have poorly controlled CV risk factors at baseline. Hence, there is an urgent need to address gaps in preventing and managing CVD in PCa patients. Screening and optimizing CV risk factors and CVD in patients undergoing ADT are essential to reduce CV mortality, the leading non-cancer cause of death in PCa survivors. The risk of CV morbidity and mortality can be further mitigated by considering the patient's cardiovascular risk profile when deciding the choice and duration of ADT. A multidisciplinary team-based approach is crucial to achieve the best outcomes for PCa patients undergoing therapy.

CAR-T Therapy in Lymphoma Patients With Coexisting Cardiomyopathy or Cardiac Lymphomatous Involvement.

Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the management of aggressive hematologic malignancies. However, its role in patients with lymphoma and cardiac metastasis or cardiomyopathy remains undefined due to potentially life-threatening complications such as ventricular rupture, cardiac tamponade, and circulatory failure. We present a case series of patients with lymphoma and cardiomyopathy or cardiac metastasis managed with chimeric antigen receptor T-cell therapy. (Level of Difficulty: Advanced.).

Advancing Cardio-Oncology in Asia.

Cardio-oncology is an emerging multi-disciplinary field, which aims to reduce morbidity and mortality of cancer patients by preventing and managing cancer treatment-related cardiovascular toxicities. With the exponential growth in cancer and cardiovascular diseases in Asia, there is an emerging need for cardio-oncology awareness among physicians and country-specific cardio-oncology initiatives. In this state-of-the-art review, we sought to describe the burden of cancer and cardiovascular disease in Asia, a region with rich cultural and socio-economic diversity. From describing the uniqueness and challenges (such as socio-economic disparity, ethnical and racial diversity, and limited training opportunities) in establishing cardio-oncology in Asia, and outlining ways to overcome any barriers, this article aims to help advance the field of cardio-oncology in Asia.

Modern-era radiotherapy and ischaemic heart disease-related mortality outcomes in Asian breast-cancer patients.

Introduction: Left-sided breast-cancer patients treated with adjuvant radiotherapy (RT) before the 1990s were associated with increased risk of cardiac mortality. Modern RT techniques have since improved, resulting in lower radiation doses to the heart. However, concerns regarding cardiac toxicity remain. In a retrospective cohort study, we compare the ischaemic heart disease (IHD)-related mortality of left-sided versus right-sided breast-cancer patients. We present the results of the cardiac mortality and all-cause mortality risk of Asian breast-cancer survivors treated with RT in Singapore. Material and methods: A total of 14,419 Asian women from a single institution were treated for breast cancer from 2000 to 2016. A systematic mortality follow-up was conducted until December 2015. The effect of breast cancer laterality on IHD-related mortality and on overall mortality was investigated. Mean heart doses were recorded for patients from 2010-2016. Results: In the irradiated group (n = 9556), we found no difference in IHD-related mortality or overall mortality when comparing the left- and right-sided breast cancers. The hazard ratio of cardiac mortality for left-sided versus right-sided RT was 0.94 (95% CI: 0.64-1.38). The hazard ratio for all-cause mortality was 1.03 (95% CI: 0.94-1.13). Conclusions: Our study of Asian cancer patients did not reveal a significant increase in the risk of IHD-related mortality or overall mortality comparing left- vs. right-sided breast cancers in modern-era RT.

Cardiovascular toxicities of androgen deprivation therapy in Asian men with localized prostate cancer after curative radiotherapy: a registry-based observational study.

BACKGROUND: Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, and the risk relates to pre-existing risk factors and ADT modalities. Despite ethnic differences in the prevalence of CV risk factors and variations of CV mortality, data on ADT-related cardiotoxicities in the Asian population remain inconclusive. Our registry-based study investigated ADT-related major adverse cardiovascular events (MACE) after primary or salvage RT. METHODS: Our study combined two prospectively established registry databases from National Cancer Center Singapore and National Heart Center Singapore. The primary endpoint is time to first MACE after treatment. MACE is defined as myocardial infarction, stroke, unstable angina, or cardiovascular death. Two types of propensity score adjustments, including ADT propensity score as a covariate in the multivariable regression model and propensity score weighting, were applied to balance baseline features and CV risk factors between RT alone and RT + ADT groups. RESULTS: From 2000 to 2019, 1940 patients received either RT alone (n = 494) or RT + ADT (n = 1446) were included. After a median follow-up of 10 years (RT) and 7.2 years (RT+ ADT), the cumulative incidence of MACE at 1, 3 and 9 years was 1.2, 5 and 16.2% in RT group, and 1.1, 5.2 and 17.6% in RT + ADT group, respectively. There were no differences in the incidence of MACE between 2 groups (HR 1.01, 95% CI 0.78-1.30, p = 0.969). Pre-treatment CV risk factors were common (80%), and CV disease (15.9%) was the second leading cause of death after prostate cancer (21.1%). On univariate analysis, older age, Indians and Malays, pre-existing CV risk factors, and history of MACE were associated with higher MACE risk. After propensity score adjustments, there remained no significant differences in MACE risk between RT + ADT and RT group on multivariable analysis. CONCLUSIONS: In our registry-based study, ADT is not associated with increased risk of major cardiovascular events among Southeast Asian men with prostate cancer after curative radiotherapy.

The role of multimodality imaging in diagnosing acute perimyocarditis secondary to Crohn's disease.

BACKGROUND: Acute perimyocarditis is a rare extra-intestinal manifestation in Crohn's disease which required multimodality imaging to confirm the diagnosis. Here we present a case of acute perimyocarditis as the first presentation of Crohn's disease. To date, this is the first case presentation reporting the use of 18F-FDG PET/CT Scan for diagnosing such condition. CASE PRESENTATION: A 25-year-old male presented to our hospital with severe persistent pleuritic sharp left-sided chest pain. This was his second hospital admission in the past 4 months for chest pain and diarrhea. At the first hospitalization, he was diagnosed with viral perimyocarditis and irritable bowel syndrome. Laboratory findings, electrocardiogram, and cardiac magnetic resonance imaging results confirm the diagnostic of perimyocarditis. Virology, bacteriology, parasitology, and autoimmune evaluations were unremarkable. Colonoscopy, colorectal biopsy, and 18FGD PET findings confirmed manifestation of perimyocarditis, Crohn's disease, and negative for sarcoidosis. CONCLUSIONS: Looking at the overall clinical picture and investigation results of colonoscopy, colorectal biopsy findings, as well as multi-modality imaging with echocardiography, 18FDG PET-scan and CMRI, the patient was diagnosed to have perimyocarditis attending Chron's disease flare up as a rare extra-intestinal manifestation.

Successful extracorporeal liver dialysis for the treatment of trimethoprim-sulfamethoxazole-induced fulminant hepatic failure.

Trimethoprim-sulfamethoxazole (TMP-SMZ) is a commonly used antibiotic that has been associated with drug rash with eosinophilia and systemic symptoms (DRESS) syndrome. DRESS syndrome is characterised by fever, rash, lymphadenopathy, eosinophilia and one or more major organ involvement. Although rare, TMP-SMZ is a recognised cause of fulminant hepatic failure. We report a 17-year-old Chinese male adolescent who presented with fever, myalgia, generalised maculopapular rash and lymphadenopathy after taking TMP-SMZ for acne vulgaris. He subsequently developed hepatic encephalopathy and was worked up for urgent liver transplantation. He responded well to extracorporeal liver dialysis (originally intended as a bridging therapy) and subsequently recovered without the need for liver transplantation. This case report highlights the importance of early recognition of TMP-SMZ-induced DRESS syndrome and the need for early discontinuation of the drug in the affected patient. Extracorporeal liver dialysis and transplantation should be considered in the management of TMP-SMZ-induced fulminant hepatic failure.

Prevalence of electrocardiographic abnormalities in an unselected young male multi-ethnic South-East Asian population undergoing pre-participation cardiovascular screening: results of the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol.

AIMS: Resting 12-lead electrocardiograms (ECGs) have been employed in the pre-participation evaluation of young asymptomatic subjects to detect pre-existing heart diseases. Although the incorporation of routine ECG in pre-participation screening remains controversial, there is increasing evidence that cardiomyopathies and ion channelopathies have ECG changes as the initial manifestation. The causes of sudden cardiac death in young people show significant geographical variation. We aim to determine the prevalence and spectrum of ECG abnormalities in a young male South-East Asian population. METHODS AND RESULTS: The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE) protocol is an ECG-based pre-participation cardiac screening programme modelled after the Italian system. From October 2008 to May 2009, a total of 18 476 young male conscripts (mean age 19.5 years old, range 16-27) underwent mandatory pre-enlistment medical screening at a single medical facility. Subjects with abnormal ECG findings were classified into two groups: Group A had ECG changes that fulfilled a pre-specified checklist to screen for hypertrophic cardiomyopathy and were referred for transthoracic echocardiogram; Group B had other ECG abnormalities [such as Brugada pattern, Wolff-Parkinson-White (WPW) pattern, long QTc] and were referred for secondary screening at a tertiary institution. Of the 18 476 subjects screened, 7.0% (n= 1285) had ECG abnormalities. Of note, 19 (0.10%) had Brugada pattern, 25 (0.14%) had WPW pattern, and 31 (0.17%) had prolonged QT interval on ECG. The prevalence of ECG abnormalities was significantly higher in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). CONCLUSION: The prevalence of ECG abnormalities in a young, South-East Asian male population was 7.0%. There were significant ethnic differences, with ECG abnormalities more prevalent in Chinese than in South Asians (7.2 vs. 5.7%, P= 0.003). The inclusion of universal ECG, in addition to history and physical examination, may increase the sensitivity of a cardiovascular screening programme. Knowledge of the spectrum and prevalence of ECG abnormalities and disease conditions would be pivotal in designing customized screening programmes.

Prevalence of hypertrophic cardiomyopathy on an electrocardiogram-based pre-participation screening programme in a young male South-East Asian population: results from the Singapore Armed Forces Electrocardiogram and Echocardiogram screening protocol.

AIMS: Hypertrophic cardiomyopathy is a leading cause of sudden cardiac death (SCD) in young people in the USA. Pre-participation screening for athletes might reduce the incidence of SCD. In Singapore, military service is compulsory for all young able-bodied male citizens. The Singapore Armed Forces Electrocardiogram and Echocardiogram (SAFE) pre-participation screening protocol based on the Italian programme was introduced. This study evaluates the prevalence of hypertrophic cardiomyopathy (HCM) in a young male South-East Asian population. METHODS AND RESULTS: From October 2008 to May 2009, all male military conscripts underwent pre-participation screening. For all conscripts whose electrocardiogram (ECG) findings fulfilled any of these pre-specified criteria (Group A), direct referral for a transthoracic echocardiogram was mandatory. Conscripts with ECG findings other than pre-specified criteria (e.g. T-wave inversions, repolarization abnormalities) were referred for secondary screening by cardiologists (Group B), which could include echocardiography. Out of 18 476 subjects screened during the study period, 988 (5.3%) subjects were fast tracked for echocardiogram (Group A). Of them, there were three (0.3%) cases with severe abnormalities; there was one case each of HCM, bicuspid aortic valve with significant aortic valve regurgitation, and atrial septal defect with right ventricular systolic dysfunction. The patient with HCM had left axis deviation on ECG. None of the 215 patients who underwent echocardiography following cardiology consult (Group B) had HCM. CONCLUSION: The prevalence of HCM in our young male population (mean age 19.5, range 16-27) using an ECG-based screening protocol was 0.005%; this appeared lower than published data from other geographical cohorts. Possible explanations include a later age of phenotypic manifestation in our population, limitations of the ECG criteria for screening, or a truly lower prevalence of HCM. More population-based longitudinal studies would be needed to ascertain the true prevalence of HCM in our South-East Asian population.