The Impact of Bariatric Surgery on Coronary Microvascular Function Assessed Using Automated Quantitative Perfusion CMR.

BACKGROUND: Coronary microvascular function is impaired in patients with obesity, contributing to myocardial dysfunction and heart failure. Bariatric surgery decreases cardiovascular mortality and heart failure, but the mechanisms are unclear. OBJECTIVES: The authors studied the impact of bariatric surgery on coronary microvascular function in patients with obesity and its relationship with metabolic syndrome. METHODS: Fully automated quantitative perfusion cardiac magnetic resonance and metabolic markers were performed before and 6 months after bariatric surgery. RESULTS: Compared with age- and sex-matched healthy volunteers, 38 patients living with obesity had lower stress myocardial blood flow (MBF) (P = 0.001) and lower myocardial perfusion reserve (P < 0.001). A total of 27 participants underwent paired follow-up 6 months post-surgery. Metabolic abnormalities reduced significantly at follow-up including mean body mass index by 11 ± 3 kg/m2 (P < 0.001), glycated hemoglobin by 9 mmol/mol (Q1-Q3: 4-19 mmol/mol; P < 0.001), fasting insulin by 142 ± 131 pmol/L (P < 0.001), and hepatic fat fraction by 5.6% (2.6%-15.0%; P < 0.001). Stress MBF increased by 0.28 mL/g/min (-0.02 to 0.75 mL/g/min; P = 0.003) and myocardial perfusion reserve by 0.13 (-0.25 to 1.1; P = 0.036). The increase in stress MBF was lower in those with preoperative type 2 diabetes mellitus (0.1 mL/g/min [-0.09 to 0.46 mL/g/min] vs 0.75 mL/g/min [0.31-1.25 mL/g/min]; P = 0.002). Improvement in stress MBF was associated with reduction in fasting insulin (beta = -0.45 [95% CI: -0.05 to 0.90]; P = 0.03). CONCLUSIONS: Coronary microvascular function is impaired in patients with obesity, but can be improved significantly with bariatric surgery. Improvements in microvascular function are associated with improvements in insulin resistance but are attenuated in those with preoperative type 2 diabetes mellitus.

Pericarditis and Cardiac Tamponade in Patients Treated with First and Second Generation Bruton Tyrosine Kinase Inhibitors: An Underappreciated Risk.

Introduction: The introduction of Bruton's tyrosine kinase (BTK) inhibitors significantly improved the management of chronic lymphocytic leukemia (CLL). However, BTK carry the risk of cardiotoxicity, which is not only limited to atrial fibrillation. Case Reports. We report three cases of patients on BTK inhibitors who developed acute pericarditis and cardiac tamponade. We report the first patient who developed this complication on treatment with zanubrutinib. This patient's treatment was changed to zanubrutinib due to atrial fibrillation. Shortly after cardioversion, he developed cardiac tamponade and shock. He underwent pericardiocentesis, received treatment for acute pericarditis with steroids and colchicine, and made a full recovery. We also report two further cases, both involving patients treated with ibrutinib. These patients also developed acute pericarditis and cardiac tamponade and required pericardiocentesis. All three patients discontinued BTK therapy following the events. Conclusions: These three cases highlight the rare but potentially life-threatening risk of cardiac tamponade which can occur even with newer generations of BTK inhibitors. Haemato-oncologists should remain vigilant in patients who report dyspnea or who show sinus tachycardia on routine electrocardiography. Even in the absence of classical clinical signs of tamponade, patients require urgent evaluation with echocardiography and potentially emergency pericardiocentesis.

Use of heart failure medical therapy before and after a cancer diagnosis: A longitudinal study.

AIMS: We aim to evaluate change in the use of prognostic guideline-directed medical therapies (GDMTs) for heart failure (HF) before and after a cancer diagnosis as well as the matched non-cancer controls, including renin-angiotensin-system inhibitors (RASIs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs). METHODS AND RESULTS: We conducted a longitudinal study in patients with HF in the UK Clinical Practice Research Datalink between 2005 and 2021. We selected patients with probable HF with reduced ejection fraction (HFrEF) based on diagnostic and prescription records. We described the longitudinal trends in the use and dosing of GDMTs before and after receiving an incident cancer diagnosis. HF patients with cancer were matched with a 1:1 ratio to HF patients without cancer to investigate the association between cancer diagnosis and treatment adherence, persistence, initiation, and dose titration as odds ratios (ORs) with 95% confidence intervals (CIs) using multivariable logistic regression models. Of 8504 eligible HFrEF patients with incident cancer, 4890 were matched to controls without cancer. The mean age was 75.7 (±8.4) years and 73.9% were male. In the 12 months following a cancer diagnosis, patients experienced reductions in the use and dosing of GDMT. Compared with the non-cancer controls, patients with cancer had higher risks for poor adherence for all three medication classes (RASIs: OR = 1.51, 95% CI = 1.35-1.68; beta-blockers: OR = 1.22, 95% CI = 1.08-1.37; MRAs: OR = 1.31, 95% CI = 1.08-1.59) and poor persistence (RASIs: OR = 2.04, 95% CI = 1.75-2.37; beta-blockers: OR = 1.35, 95% CI = 1.12-1.63; MRAs: OR = 1.49, 95% CI = 1.16-1.93), and higher risks for dose down-titration for RASIs (OR = 1.69, 95% CI = 1.40-2.04) and beta-blockers (OR = 1.31, 95% CI = 1.05-1.62). Cancer diagnosis was not associated with treatment initiation or dose up-titration. Event rates for HF hospitalization and mortality were higher in patients with poor adherence or persistence to GDMTs. CONCLUSIONS: Following a cancer diagnosis, patients with HFrEF were more likely to have reduced use of GDMTs for HF.

Predicting cardiovascular events with fluoropyrimidine chemotherapy using a standard cardiovascular risk calculator.

AIMS: Fluoropyrimidine chemotherapy is important for treatment of many solid tumours but is associated with cardiotoxicity. The relationship of fluoropyrimidine-associated cardiotoxicity (FAC) with conventional cardiovascular (CV) risk factors is poorly understood, and standard cardiovascular risk scores are not validated in this context. METHODS AND RESULTS: Single-centre retrospective study of patients treated with fluoropyrimidine chemotherapy using electronic health records for cardiovascular risk factors (and calculation of QRISK3 score), cancer treatment, and clinical outcomes. FAC was defined by cardiovascular events during or within 3 months of fluoropyrimidine treatment, and Cox regression was used to assess associations of CV risk and cancer treatment with FAC. One thousand eight hundred ninety-eight patients were included (45% male; median age 64 years), with median follow up 24.5 (11.5-48.3 months); 52.7% of patients were at moderate or high baseline CV risk (QRISK3 score >10%) Cardiovascular events occurred in 3.1% (59/1898)-most commonly angina (64.4%, 38/59) and atrial fibrillation (13.6%, 8/59), with 39% events during cycle one of treatment. In univariable analysis, QRISK3 score >20% was significantly associated with incident FAC (HR 2.25, 95% CI 1.11-4.93, P = 0.03). On multivariable analysis, beta-blocker use (HR 1.04, 95% CI 1.00-1.08, P = 0.04) and higher BMI (HR 2.33, 95% CI 1.04-5.19, P = 0.04) were independently associated with incident CV events. Thirty-two of the 59 patients with FAC were subsequently rechallenged with fluoropyrimidine chemotherapy, with repeat CV events in 6% (2/32). Incident FAC did not affect overall survival (P = 0.50). CONCLUSIONS: High BMI and use of beta-blockers are associated with risk of CV events during fluoropyrimidine chemotherapy. QRISK3 score may also play a role in identifying patients at high risk of CV events during fluoropyrimidine chemotherapy. Re-challenge with further fluoropyrimidine chemotherapy can be considered in patients following CV events during prior treatment.

Effect of statin treatment on the risk of cancer in patients with heart failure: A target trial emulation study.

PURPOSE: A recent observational study suggested statins could reduce cancer diagnosis in patients with heart failure (HF). The findings need to be validated using robust epidemiological methods. This study aimed to evaluate the effect of statin treatment on the risk of cancer in patients with HF. METHODS: We conducted two target trial emulations using primary care data from IQVIA Medical Research Database-UK (2000 to 2019) with a clone-censor-weight design. The first emulated trial addressed the treatment initiation effect: initiating within 1 year versus not initiating a statin after the HF diagnosis. The second emulated trial addressed the cumulative exposure effect: continuing a statin for ≤3 years, 3-6 years, and >6 years after initiation. The study outcomes were any incident cancer and site-specific cancer diagnoses. Weighted pooled logistic regression models were used to estimate 10-year risk ratios (RR). 95% confidence intervals (CIs) were estimated using non-parametric bootstrapping. RESULTS: The first emulated trial showed that, compared to no statin, statins did not reduce the cancer risk in patients with HF (RR, 1.05; 95% CI, 0.94-1.15). The second emulated trial showed that, compared to treatment ≤3 years, statins with longer durations did not reduce the cancer risk (3-6 years: RR, 0.94; 95% CI, 0.70-1.33. >6 years: RR, 0.97; 95% CI, 0.79-1.26). No significant risk difference was observed on any site-specific cancer diagnoses. CONCLUSIONS: The results from the target trial emulations suggest that statin treatment is not associated with cancer risk in patients with HF.

The effect of CTCA guided selective invasive graft assessment on coronary angiographic parameters and outcomes: Insights from the BYPASS-CTCA trial.

BACKGROUND: Computed tomography cardiac angiography (CTCA) is recommended for the evaluation of patients with prior coronary artery bypass graft (CABG) surgery. The BYPASS-CTCA study demonstrated that CTCA prior to invasive coronary angiography (ICA) in CABG patients leads to significant reductions in procedure time and contrast-induced nephropathy (CIN), alongside improved patient satisfaction. However, whether CTCA information was used to facilitate selective graft cannulation at ICA was not protocol mandated. In this post-hoc analysis we investigated the influence of CTCA facilitated selective graft assessment on angiographic parameters and study endpoints. METHODS: BYPASS-CTCA was a randomized controlled trial in which patients with previous CABG referred for ICA were randomized to undergo CTCA prior to ICA, or ICA alone. In this post-hoc analysis we assessed the impact of selective ICA (grafts not invasively cannulated based on the CTCA result) following CTCA versus non-selective ICA (imaging all grafts irrespective of CTCA findings). The primary endpoints were ICA procedural duration, incidence of CIN, and patient satisfaction post-ICA. Secondary endpoints included the incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: In the CTCA cohort (n â€‹= â€‹343), 214 (62.4%) patients had selective coronary angiography performed, whereas 129 (37.6%) patients had non-selective ICA. Procedure times were significantly reduced in the selective CTCA â€‹+ â€‹ICA group compared to the non-selective CTCA â€‹+ â€‹ICA group (-5.82min, 95% CI -7.99 to -3.65, p â€‹< â€‹0.001) along with reduction of CIN (1.5% vs 5.8%, OR 0.26, 95% CI 0.10 to 0.98). No difference was seen in patient satisfaction with the ICA, however procedural complications (0.9% vs 4.7%, OR 0.21, 95% CI 0.09-0.87) and 1-year major adverse cardiac events (13.1% vs 20.9%, HR 0.55, 95% CI 0.32-0.96) were significantly lower in the selective group. CONCLUSIONS: In patients with prior CABG, CTCA guided selective angiographic assessment of bypass grafts is associated with improved procedural parameters, lower complication rates and better 12-month outcomes. Taken in addition to the main findings of the BYPASS-CTCA trial, these results suggest a synergistic approach between CTCA and ICA should be considered in this patient group. REGISTRATION: ClinicalTrials.gov, NCT03736018.

Myocardial perfusion in cardiac amyloidosis.

AIMS: Cardiac involvement is the main driver of clinical outcomes in systemic amyloidosis and preliminary studies support the hypothesis that myocardial ischaemia contributes to cellular damage. The aims of this study were to assess the presence and mechanisms of myocardial ischaemia using cardiovascular magnetic resonance (CMR) with multiparametric mapping and histopathological assessment. METHODS AND RESULTS: Ninety-three patients with cardiac amyloidosis (CA) (light-chain amyloidosis n = 42, transthyretin amyloidosis n = 51) and 97 without CA (three-vessel coronary disease [3VD] n = 47, unobstructed coronary arteries n = 26, healthy volunteers [HV] n = 24) underwent quantitative stress perfusion CMR with myocardial blood flow (MBF) mapping. Twenty-four myocardial biopsies and three explanted hearts with CA were analysed histopathologically. Stress MBF was severely reduced in patients with CA with lower values than patients with 3VD, unobstructed coronary arteries and HV (CA: 1.04 ± 0.51 ml/min/g, 3VD: 1.35 ± 0.50 ml/min/g, unobstructed coronary arteries: 2.92 ± 0.52 ml/min/g, HV: 2.91 ± 0.73 ml/min/g; CA vs. 3VD p = 0.011, CA vs. unobstructed coronary arteries p < 0.001, CA vs. HV p < 0.001). Myocardial perfusion abnormalities correlated with amyloid burden, systolic and diastolic function, structural parameters and blood biomarkers (p < 0.05). Biopsies demonstrated abnormal vascular endothelial growth factor staining in cardiomyocytes and endothelial cells, which may be related to hypoxia conditions. Amyloid infiltration in intramural arteries was associated with severe lumen reduction and severe reduction in capillary density. CONCLUSION: Cardiac amyloidosis is associated with severe inducible myocardial ischaemia demonstrable by histology and CMR stress perfusion mapping. Histological evaluation indicates a complex pathophysiology, where in addition to systolic and diastolic dysfunction, amyloid infiltration of the epicardial arteries and disruption and rarefaction of the capillaries play a role in contributing to myocardial ischaemia.

Imaging in patients with cardiovascular implantable electronic devices: part 1-imaging before and during device implantation. A clinical consensus statement of the European Association of Cardiovascular Imaging (EACVI) and the European Heart Rhythm Association (EHRA) of the ESC.

More than 500 000 cardiovascular implantable electronic devices (CIEDs) are implanted in the European Society of Cardiology countries each year. The role of cardiovascular imaging in patients being considered for CIED is distinctly different from imaging in CIED recipients. In the former group, imaging can help identify specific or potentially reversible causes of heart block, the underlying tissue characteristics associated with malignant arrhythmias, and the mechanical consequences of conduction delays and can also aid challenging lead placements. On the other hand, cardiovascular imaging is required in CIED recipients for standard indications and to assess the response to device implantation, to diagnose immediate and delayed complications after implantation, and to guide device optimization. The present clinical consensus statement (Part 1) from the European Association of Cardiovascular Imaging, in collaboration with the European Heart Rhythm Association, provides comprehensive, up-to-date, and evidence-based guidance to cardiologists, cardiac imagers, and pacing specialists regarding the use of imaging in patients undergoing implantation of conventional pacemakers, cardioverter defibrillators, and resynchronization therapy devices. The document summarizes the existing evidence regarding the use of imaging in patient selection and during the implantation procedure and also underlines gaps in evidence in the field. The role of imaging after CIED implantation is discussed in the second document (Part 2).

Computed Tomography Cardiac Angiography Before Invasive Coronary Angiography in Patients With Previous Bypass Surgery: The BYPASS-CTCA Trial.

BACKGROUND: Patients with previous coronary artery bypass grafting often require invasive coronary angiography (ICA). However, for these patients, the procedure is technically more challenging and has a higher risk of complications. Observational studies suggest that computed tomography cardiac angiography (CTCA) may facilitate ICA in this group, but this has not been tested in a randomized controlled trial. METHODS: This study was a single-center, open-label randomized controlled trial assessing the benefit of adjunctive CTCA in patients with previous coronary artery bypass grafting referred for ICA. Patients were randomized 1:1 to undergo CTCA before ICA or ICA alone. The co-primary end points were procedural duration of the ICA (defined as the interval between local anesthesia administration for obtaining vascular access and removal of the last catheter), patient satisfaction after ICA using a validated questionnaire, and the incidence of contrast-induced nephropathy. Linear regression was used for procedural duration and patient satisfaction score; contrast-induced nephropathy was analyzed using logistic regression. We applied the Bonferroni correction, with P<0.017 considered significant and 98.33% CIs presented. Secondary end points included incidence of procedural complications and 1-year major adverse cardiac events. RESULTS: Over 3 years, 688 patients were randomized with a median follow-up of 1.0 years. The mean age was 69.8±10.4 years, 108 (15.7%) were women, 402 (58.4%) were White, and there was a high burden of comorbidity (85.3% hypertension and 53.8% diabetes). The median time from coronary artery bypass grafting to angiography was 12.0 years, and there were a median of 3 (interquartile range, 2 to 3) grafts per participant. Procedure duration of the ICA was significantly shorter in the CTCA+ICA group (CTCA+ICA, 18.6±9.5 minutes versus ICA alone, 39.5±16.9 minutes [98.33% CI, -23.5 to -18.4]; P<0.001), alongside improved mean ICA satisfaction scores (1=very good to 5=very poor; -1.1 difference [98.33% CI, -1.2 to -0.9]; P<0.001), and reduced incidence of contrast-induced nephropathy (3.4% versus 27.9%; odds ratio, 0.09 [98.33% CI, 0.04-0.2]; P<0.001). Procedural complications (2.3% versus 10.8%; odds ratio, 0.2 [95% CI, 0.1-0.4]; P<0.001) and 1-year major adverse cardiac events (16.0% versus 29.4%; hazard ratio, 0.4 [95% CI, 0.3-0.6]; P<0.001) were also lower in the CTCA+ICA group. CONCLUSIONS: For patients with previous coronary artery bypass grafting, CTCA before ICA leads to reductions in procedure time and contrast-induced nephropathy, with improved patient satisfaction. CTCA before ICA should be considered in this group of patients. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03736018.

Tracking Treatment Response in Cardiac Light-Chain Amyloidosis With Native T1 Mapping.

Importance: Cardiac magnetic resonance (CMR) imaging-derived extracellular volume (ECV) mapping, generated from precontrast and postcontrast T1, accurately determines treatment response in cardiac light-chain amyloidosis. Native T1 mapping, which can be derived without the need for contrast, has demonstrated accuracy in diagnosis and prognostication, but it is unclear whether serial native T1 measurements could also track the cardiac treatment response. Objective: To assess whether native T1 mapping can measure the cardiac treatment response and the association between changes in native T1 and prognosis. Design, Setting, and Participants: This single-center cohort study evaluated patients diagnosed with cardiac light-chain amyloidosis (January 2016 to December 2020) who underwent CMR scans at diagnosis and a repeat scan following chemotherapy. Analysis took place between January 2016 and October 2022. Main Outcomes and Measures: Comparison of biomarkers and cardiac imaging parameters between patients with a reduced, stable, or increased native T1 and association between changes in native T1 and mortality. Results: The study comprised 221 patients (mean [SD] age, 64.7 [10.6] years; 130 male [59%]). At 6 months, 183 patients (mean [SD] age, 64.8 [10.5] years; 110 male [60%]) underwent repeat CMR imaging. Reduced native T1 of 50 milliseconds or more occurred in 8 patients (4%), all of whom had a good hematological response; by contrast, an increased native T1 of 50 milliseconds or more occurred in 42 patients (23%), most of whom had a poor hematological response (27 [68%]). At 12 months, 160 patients (mean [SD] age, 63.8 [11.1] years; 94 male [59%]) had a repeat CMR scan. A reduced native T1 occurred in 24 patients (15%), all of whom had a good hematological response, and was associated with a reduction in N-terminal pro-brain natriuretic peptide (median [IQR], 2638 [913-5767] vs 423 [128-1777] ng/L; P < .001), maximal wall thickness (mean [SD], 14.8 [3.6] vs 13.6 [3.9] mm; P = .009), and E/e' (mean [SD], 14.9 [6.8] vs 12.0 [4.0]; P = .007), improved longitudinal strain (mean [SD], -14.8% [4.0%] vs -16.7% [4.0%]; P = .004), and reduction in both myocardial T2 (mean [SD], 52.3 [2.9] vs 49.4 [2.0] milliseconds; P < .001) and ECV (mean [SD], 0.47 [0.07] vs 0.42 [0.08]; P < .001). At 12 months, an increased native T1 occurred in 24 patients (15%), most of whom had a poor hematological response (17 [71%]), and was associated with an increased N-terminal pro-brain natriuretic peptide (median [IQR], 1622 [554-5487] vs 3150 [1161-8745] ng/L; P = .007), reduced left ventricular ejection fraction (mean [SD], 65.8% [11.4%] vs 61.5% [12.4%]; P = .009), and an increase in both myocardial T2 (mean [SD], 52.5 [2.7] vs 55.3 [4.2] milliseconds; P < .001) and ECV (mean [SD], 0.48 [0.09] vs 0.56 [0.09]; P < .001). Change in myocardial native T1 at 6 months was independently associated with mortality (hazard ratio, 2.41 [95% CI, 1.36-4.27]; P = .003). Conclusions and Relevance: Changes in native T1 in response to treatment, reflecting a composite of changes in T2 and ECV, are associated with in changes in traditional markers of cardiac response and associated with mortality. However, as a single-center study, these results require external validation in a larger cohort.

Burden and prognostic impact of cardiovascular disease in patients with cancer.

The number of patients at the intersection of cancer and cardiovascular disease (CVD) is increasing, reflecting ageing global populations, rising burden of shared cardiometabolic risk factors, and improved cancer survival. Many cancer treatments carry a risk of cardiotoxicity. Baseline cardiovascular risk assessment is recommended in all patients with cancer and requires consideration of individual patient risk and the cardiotoxicity profile of proposed anticancer therapies. Patients with pre-existing CVD are potentially at high or very high risk of cancer-therapy related cardiovascular toxicity. The detection of pre-existing CVD should prompt cardiac optimisation and planning of surveillance during cancer treatment. In patients with severe CVD, the risk of certain cancer therapies may be prohibitively high. Such decisions require multidisciplinary discussion with consideration of alternative anti-cancer therapies, risk-benefit assessment, and patient preference. Current practice is primarily guided by expert opinion and data from select clinical cohorts. There is need for development of a stronger evidence base to guide clinical practice in cardio-oncology. The establishment of multicentre international registries and national-level healthcare data linkage projects are important steps towards facilitating enrichment of cardio-oncology research programmes. In this narrative review, we consider epidemiological trends of cancer and CVD comorbidities and the impact of their co-occurrence on clinical outcomes, current approach to supporting cancer patients with pre-existing CVD and gaps in existing knowledge.

Tracking Multiorgan Treatment Response in Systemic AL-Amyloidosis With Cardiac Magnetic Resonance Derived Extracellular Volume Mapping.

BACKGROUND: Systemic light chain amyloidosis is a multisystem disorder that commonly involves the heart, liver, and spleen. Cardiac magnetic resonance with extracellular volume (ECV) mapping provides a surrogate measure of the myocardial, liver, and spleen amyloid burden. OBJECTIVES: The purpose of this study was to assess multiorgan response to treatment using ECV mapping, and assess the association between multiorgan treatment response and prognosis. METHODS: The authors identified 351 patients who underwent baseline serum amyloid-P-component (SAP) scintigraphy and cardiac magnetic resonance at diagnosis, of which 171 had follow-up imaging. RESULTS: At diagnosis, ECV mapping demonstrated that 304 (87%) had cardiac involvement, 114 (33%) significant hepatic involvement, and 147 (42%) significant splenic involvement. Baseline myocardial and liver ECV independently predict mortality (myocardial HR: 1.03 [95% CI: 1.01-1.06]; P = 0.009; liver HR: 1.03; [95% CI: 1.01-1.05]; P = 0.001). Liver and spleen ECV correlated with amyloid load assessed by SAP scintigraphy (R = 0.751; P < 0.001; R = 0.765; P < 0.001, respectively). Serial measurements demonstrated ECV correctly identified changes in liver and spleen amyloid load derived from SAP scintigraphy in 85% and 82% of cases, respectively. At 6 months, more patients with a good hematologic response had liver (30%) and spleen (36%) ECV regression than myocardial regression (5%). By 12 months, more patients with a good response demonstrated myocardial regression (heart 32%, liver 30%, spleen 36%). Myocardial regression was associated with reduced median N-terminal pro-brain natriuretic peptide (P < 0.001), and liver regression with reduced median alkaline phosphatase (P = 0.001). Changes in myocardial and liver ECV, 6 months after initiating chemotherapy, independently predict mortality (myocardial HR: 1.11 [95% CI: 1.02-1.20]; P = 0.011; liver HR: 1.07 [95% CI: 1.01-1.13]; P = 0.014). CONCLUSIONS: Multiorgan ECV quantification accurately tracks treatment response and demonstrates different rates of organ regression, with the liver and spleen regressing more rapidly than the heart. Baseline myocardial and liver ECV and changes at 6 months independently predict mortality, even after adjusting for traditional predictors of prognosis.

Cardiovascular risk in chronic myeloid leukaemia: A multidisciplinary consensus on screening and management.

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have become the mainstay of treatment for chronic myeloid leukaemia (CML), but cardiovascular (CV) risk and exacerbation of underlying risk factors associated with TKIs have become widely debated. Real-world evidence reveals little application of CV risk factor screening or continued monitoring within UK CML management. This consensus paper presents practical recommendations to assist healthcare professionals in conducting CV screening/comorbidity management for patients receiving TKIs. METHODS: We conducted a multidisciplinary panel meeting and two iterative surveys involving 10 CML specialists: five haematologists, two cardio-oncologists, one vascular surgeon, one haemato-oncology pharmacist and one specialist nurse practitioner. RESULTS: The panel recommended that patients commencing second-/third-generation TKIs undergo formal CV risk assessment at baseline, with additional investigations and involvement of cardiologists/vascular surgeons for those with high CV risk. During treatment, patients should undergo CV monitoring, with the nature and frequency of testing dependent on TKI and baseline CV risk. For patients who develop CV adverse events, decision-making around TKI interruption, cessation or change should be multidisciplinary and balance CV and haematological risk. CONCLUSION: The panel anticipates these recommendations will support healthcare professionals in implementing CV risk screening and monitoring, broadly and consistently, and thereby help optimise TKI treatment for CML.

Pericardial Fluid Analysis in Diagnosis and Prognosis of Patients Who Underwent Pericardiocentesis.

In this study, we aimed to examine the diagnostic yield of pericardial fluid biochemistry and cytology and their prognostic significance in patients with percutaneously drained pericardial effusions, with and without malignancy. This is a single-center, retrospective study of patients who underwent pericardiocentesis between 2010 and 2020. Data were extracted from electronic patient records, including procedural information, underlying diagnosis, and laboratory results. Patients were grouped into those with and without underlying malignancy. A Cox proportional hazards model was used to analyze the association of variables with mortality. The study included 179 patients; 50% had an underlying malignancy. There were no significant differences in pericardial fluid protein and lactate dehydrogenase between the 2 groups. Diagnostic yield from pericardial fluid analysis was greater in the malignant group (32% vs 11%, p = 0.002); 72% of newly diagnosed malignancies had positive fluid cytology. The 1-year survival was 86% and 33% in nonmalignant and malignant groups, respectively (p <0.001). Of 17 patients who died within the nonmalignant group, idiopathic effusions were the largest group (n = 6). In malignancy, lower pericardial fluid protein and higher serum C-reactive protein were associated with increased risk of mortality. In conclusion, pericardial fluid biochemistry has limited value in determining the etiology of pericardial effusions; fluid cytology is the most important diagnostic test. Mortality in malignant pericardial effusions may be associated with lower pericardial fluid protein levels and a higher serum C-reactive protein. Nonmalignant pericardial effusions do not have a benign prognosis and close follow-up is required.

Incident cardiovascular events and imaging phenotypes in UK Biobank participants with past cancer.

OBJECTIVES: To evaluate incident cardiovascular outcomes and imaging phenotypes in UK Biobank participants with previous cancer. METHODS: Cancer and cardiovascular disease (CVD) diagnoses were ascertained using health record linkage. Participants with cancer history (breast, lung, prostate, colorectal, uterus, haematological) were propensity matched on vascular risk factors to non-cancer controls. Competing risk regression was used to calculate subdistribution HRs (SHRs) for associations of cancer history with incident CVD (ischaemic heart disease (IHD), non-ischaemic cardiomyopathy (NICM), heart failure (HF), atrial fibrillation/flutter, stroke, pericarditis, venous thromboembolism (VTE)) and mortality outcomes (any CVD, IHD, HF/NICM, stroke, hypertensive disease) over 11.8±1.7 years of prospective follow-up. Linear regression was used to assess associations of cancer history with left ventricular (LV) and left atrial metrics. RESULTS: We studied 18 714 participants (67% women, age: 62 (IQR: 57-66) years, 97% white ethnicities) with cancer history, including 1354 individuals with cardiovascular magnetic resonance. Participants with cancer had high burden of vascular risk factors and prevalent CVDs. Haematological cancer was associated with increased risk of all incident CVDs considered (SHRs: 1.92-3.56), larger chamber volumes, lower ejection fractions, and poorer LV strain. Breast cancer was associated with increased risk of selected CVDs (NICM, HF, pericarditis and VTE; SHRs: 1.34-2.03), HF/NICM death, hypertensive disease death, lower LV ejection fraction, and lower LV global function index. Lung cancer was associated with increased risk of pericarditis, HF, and CVD death. Prostate cancer was linked to increased VTE risk. CONCLUSIONS: Cancer history is linked to increased risk of incident CVDs and adverse cardiac remodelling independent of shared vascular risk factors.

Multi-Imaging Characterization of Cardiac Phenotype in Different Types of Amyloidosis.

BACKGROUND: Bone scintigraphy is extremely valuable when assessing patients with suspected cardiac amyloidosis (CA), but the clinical significance and associated phenotype of different degrees of cardiac uptake across different types is yet to be defined. OBJECTIVES: This study sought to define the phenotypes of patients with varying degrees of cardiac uptake on bone scintigraphy, across multiple types of systemic amyloidosis, using extensive characterization comprising biomarkers as well as echocardiographic and cardiac magnetic resonance (CMR) imaging. METHODS: A total of 296 patients (117 with immunoglobulin light-chain amyloidosis [AL], 165 with transthyretin amyloidosis [ATTR], 7 with apolipoprotein AI amyloidosis [AApoAI], and 7 with apolipoprotein AIV amyloidosis [AApoAIV]) underwent deep characterization of their cardiac phenotype. RESULTS: AL patients with grade 0 myocardial radiotracer uptake spanned the spectrum of CMR findings from no CA to characteristic CA, whereas AL patients with grades 1 to 3 always produced characteristic CMR features. In ATTR, the CA burden strongly correlated with myocardial tracer uptake, except in Ser77Tyr. AApoAI presented with grade 0 or 1 and disproportionate right-sided involvement. AApoAIV always presented with grade 0 and characteristic CA. AL grade 1 patients (n = 48; 100%) had characteristic CA, whereas only ATTR grade 1 patients with Ser77Tyr had characteristic CA on CMR (n = 5; 11.4%). After exclusion of Ser77Tyr, AApoAI, and AApoAIV, CMR showing characteristic CA or an extracellular volume of >0.40 in patients with grade 0 to 1 cardiac uptake had a sensitivity and specificity of 100% for AL. CONCLUSIONS: There is a wide variation in cardiac phenotype between different amyloidosis types across different degrees of cardiac uptake. The combination of CMR and bone scintigraphy can help to define the diagnostic differentials and the clinical phenotype in each individual patient.

[11C]metomidate PET-CT versus adrenal vein sampling for diagnosing surgically curable primary aldosteronism: a prospective, within-patient trial.

Primary aldosteronism (PA) due to a unilateral aldosterone-producing adenoma is a common cause of hypertension. This can be cured, or greatly improved, by adrenal surgery. However, the invasive nature of the standard pre-surgical investigation contributes to fewer than 1% of patients with PA being offered the chance of a cure. The primary objective of our prospective study of 143 patients with PA ( NCT02945904 ) was to compare the accuracy of a non-invasive test, [11C]metomidate positron emission tomography computed tomography (MTO) scanning, with adrenal vein sampling (AVS) in predicting the biochemical remission of PA and the resolution of hypertension after surgery. A total of 128 patients reached 6- to 9-month follow-up, with 78 (61%) treated surgically and 50 (39%) managed medically. Of the 78 patients receiving surgery, 77 achieved one or more PA surgical outcome criterion for success. The accuracies of MTO at predicting biochemical and clinical success following adrenalectomy were, respectively, 72.7 and 65.4%. For AVS, the accuracies were 63.6 and 61.5%. MTO was not significantly superior, but the differences of 9.1% (95% confidence interval = -6.5 to 24.1%) and 3.8% (95% confidence interval = -11.9 to 9.4) lay within the pre-specified -17% margin for non-inferiority (P = 0.00055 and P = 0.0077, respectively). Of 24 serious adverse events, none was considered related to either investigation and 22 were fully resolved. MTO enables non-invasive diagnosis of unilateral PA.

Sex differences among patients with transthyretin amyloid cardiomyopathy - from diagnosis to prognosis.

AIMS: Transthyretin amyloid cardiomyopathy (ATTR-CM) is predominantly diagnosed in men. The few available studies suggest affected women have a more favourable cardiac phenotype. We aimed to characterize sex differences among consecutive patients with non-hereditary and two prevalent forms of hereditary (h)ATTR-CM diagnosed over a 20-year period. METHODS AND RESULTS: Analysis of deep phenotyping at presentation, changes on serial echocardiography and overall prognosis were evaluated. In total, 1732 consecutive patients were studied, comprising: 1095 with wild-type (wt)ATTR-CM; 206 with T60A-hATTR-CM; and 431 with V122I-hATTR-CM. Female prevalence was greater in T60A-hATTR-CM (29.6%) and V122I-hATTR-CM (27.8%) compared to wtATTR-CM (6%). At presentation, females were 3.3 years older than males (wtATTR-CM: 81.9 vs. 77.8 years; T60A-hATTR-CM: 68.7 vs. 65.1 years; V122I-hATTR-CM: 77.1 vs. 74.9 years). Body size significantly influenced measures of disease severity; when indexed, overall structural and functional phenotype was similar between sexes, the few significant differences suggested a mildly worse phenotype in females. No significant differences were observed in both disease progression on serial echocardiography and mortality across the overall population (p = 0.459) and when divided by genotype (wtATTR-CM: p = 0.730; T60A-hATTR-CM: p = 0.161; V122I-hATTR-CM: p = 0.056). CONCLUSION: This study of a well-characterized large cohort of ATTR-CM patients did not demonstrate overall differences between sexes in either clinical phenotype, when indexed, or with respect to disease progression and prognosis. Non-indexed wall thickness measurements may have contributed to both under-representation and delays in diagnosis for affected females and highlights the potential role of utilizing indexed echocardiographic parameters for a more accurate assessment of patients at diagnosis and for disease prognostication.

Impact of Earlier Diagnosis in Cardiac ATTR Amyloidosis Over the Course of 20 Years.

BACKGROUND: Diagnostic and therapeutic advances have led to much greater awareness of transthyretin cardiac amyloidosis (ATTR-CA). We aimed to characterize changes in the clinical phenotype of patients diagnosed with ATTR-CA over the past 20 years. METHODS: This is a retrospective observational cohort study of all patients referred to the National Amyloidosis Centre (2002-2021) in whom ATTR-CA was a differential diagnosis. RESULTS: We identified 2995 patients referred with suspected ATTR-CA, of whom 1967 had a diagnosis of ATTR-CA confirmed. Analysis by 5-year periods revealed an incremental increase in referrals, with higher proportions of patients having been referred after bone scintigraphy and cardiac magnetic resonance imaging (2% versus 34% versus 51% versus 55%, chi-square P<0.001). This was accompanied by a greater number of ATTR-CA diagnoses, predominantly of the wild-type nonhereditary form, which is now the most commonly diagnosed form of ATTR-CA (0% versus 54% versus 67% versus 66%, chi-square P<0.001). Over time, the median duration of associated symptoms before diagnosis fell from 36 months between 2002 and 2006 to 12 months between 2017 and 2021 (Mann-Whitney P<0.001), and a greater proportion of patients had early-stage disease at diagnosis across the 5-year periods (National Amyloidosis Centre stage 1: 34% versus 42% versus 44% versus 53%, chi-square P<0.001). This was associated with more favorable echocardiographic parameters of structure and function, including lesser interventricular septal thickness (18.0±3.8 mm versus 17.2±2.6 mm versus 16.9±2.3 mm versus 16.6±2.4 mm, P=0.01) and higher left ventricular ejection fraction (46.0%±8.9% versus 46.8%±11.0% versus 47.8%±11.0% versus 49.5%±11.1%, P<0.001). Mortality decreased progressively during the study period (2007-2011 versus 2012-2016: hazard ratio, 1.57 [95% CI, 1.31-1.89], P<0.001; and 2012-2016 versus 2017-2021: hazard ratio, 1.89 [95% CI, 1.55-2.30], P<0.001). The proportion of patients enrolled into clinical trials and prescribed disease-modifying therapy increased over the 20-year period, but even when censoring at the trial or medication start date, year of diagnosis remained a significant predictor of mortality (2012-2016 versus 2017-2021: hazard ratio, 1.05 [95% CI, 1.03-1.07], P<0.001). CONCLUSIONS: There has been a substantial increase in ATTR-CA diagnoses, with more patients being referred after local advanced cardiac imaging. Patients are now more often diagnosed at an earlier stage of the disease, with substantially lower mortality. These changes may have important implications for initiation and outcome of therapy and urgently need to be factored into clinical trial design.