scholarly journals Coronary microcirculation damage in anthracycline cardiotoxicity

2021 ◽  
Author(s):  
Carlos Galán-Arriola ◽  
Jean Paul Vílchez-Tschischke ◽  
Manuel Lobo ◽  
Gonzalo J López ◽  
Antonio de Molina-Iracheta ◽  
...  
Keyword(s):  
Cumulative Dose ◽  
Structural Damage ◽  
Coronary Microcirculation ◽  
Cumulative Exposure ◽  
Anthracycline Cardiotoxicity ◽  
Dose Regime ◽  
Cardiac Contractile ◽  
Flow Reserve ◽  
High Cumulative Dose

Abstract Aims The aim of this study was to study changes in coronary microcirculation status during and after several cycles of anthracycline treatment. Methods and Results Large-White male pigs (n = 40) were included in different experimental protocols (ExPr.) according to anthracycline cumulative exposure (0.45 mg/kg intracoronary (IC) doxorubicin per injection) and follow-up: Control (no doxorubicin); Single injection and sacrifice either at 48 hours (ExPr. 1) or 2 weeks (ExPr. 2); Three injections two weeks apart (low cumulative dose) and sacrifice either 2 weeks (ExPr. 3) or 12 weeks (ExPr. 4) after third injection; Five injections two weeks apart (high cumulative dose) and sacrifice 8 weeks after fifth injection (ExPr. 5). All groups were assessed by serial cardiac magnetic resonance (CMR) to quantify perfusion and invasive measurement of coronary flow reserve (CFR). At the end of each protocol, animals were sacrificed for ex vivo analyses. Vascular function was further evaluated by myography in explanted coronary arteries of pigs undergoing ExPr. 3 and controls. A single doxorubicin injection had no impact on microcirculation status, excluding a direct chemical toxicity. A series of five fortnightly doxorubicin injections (high cumulative dose) triggered a progressive decline in microcirculation status, evidenced by reduced CMR-based myocardial perfusion and CFR-measured impaired functional microcirculation. In the high cumulative dose regime (ExPr. 5), microcirculation changes appeared long before any contractile defect became apparent. Low cumulative doxorubicin dose (3 biweekly injections) was not associated with any contractile defect across long-term follow-up, but provoked persistent microcirculation damage, evident soon after third dose injection. Histological and myograph evaluations confirmed structural damage to arteries of all calibers even in animals undergoing low cumulative dose regimes. Conversely, arteriole damage and capillary bed alteration occurred only after high cumulative dose regime. Conclusion Serial in vivo evaluations of microcirculation status using state-of-the-art CMR and invasive CFR show that anthracyclines treatment is associated with progressive and irreversible damage to the microcirculation. This long-persisting damage is present even in low cumulative dose regimes, which are not associated with cardiac contractile deficits. Microcirculation damage might explain some of the increased incidence of cardiovascular events in cancer survivors who received anthracyclines without showing cardiac contractile defects.

Abstract 4838: Diffuse, Marked, Reversible Impairment in Coronary Microcirculation in Stress Cardiomyopathy: A Vasodilator Stress Echo Study

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Fausto Rigo ◽  
Rosa Sicari ◽  
Rodolfo Citro ◽  
Giovanni Ossena ◽  
Paolo Buja ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Acute Phase ◽  
Right Coronary Artery ◽  
Wall Motion ◽  
Stress Cardiomyopathy ◽  
Coronary Microcirculation ◽  
Early Recovery ◽  
Flow Reserve ◽  
Stress Echo

Stress cardiomyopathy, also referred to as Takotsubo cardiomyopathy (TC) has been linked to excessive sympathetic stimulation, which can be toxic for myocytes and coronary microcirculation. Aim: To assess coronary flow reserve (CFR) in TC. Methods: 30 consecutive patients (5 males; 68±12 years) meeting diagnostic criteria for TC were evaluated with transthoracic dipyridamole (0.84 mg/kg over 6′) stress echo and Pulsed Doppler CFR assessment on mid-distal left anterior descending (LAD) and posterior descending of right coronary artery (PD). Wall Motion Score Index (WMSI) was evaluated at baseline and during stress. All patients were followed-up clinically and - on day 1, day 7 (±2 days) and at 6 months - by repeat stress echo. Twenty-one age and gender matched controls were also studied. Results: CFR was obtained in all patients on LAD and in 25 on PD. All pts showed a transient apical ballooning in the acute phase (day 1 of admission), with progression recovery of function at follow-up (WMSI, day 1=1.7±.2; day 7=1.4±.14; 6-months=1.0±0.1; p<0.001 vs day 1 and vs. day 7). When compared to controls, CFR was reduced on day 1 (upon admission) and it showed early recovery in the subacute (pre-discharge) assessment on day 7. CFR values remained stable at 6-months follow-up (see figure ). Conclusion: TC is characterized by a profound, diffuse, coronary microcirculatory disturbance in the acute phase, with early reversal to near-normal values within a few days, paralleling the functional recovery in regional wall motion. The reversible coronary microcirculatory abnormality can be observed also in the territory of right coronary artery.

scholarly journals Screening for valve disease in patients with hyperprolactinaemia disorders prescribed cabergoline: a service evaluation and literature review

2017 ◽  
Vol 8 (7) ◽  
pp. 215-229 ◽  
Author(s):  
David Gamble ◽  
Rachel Fairley ◽  
Roderick Harvey ◽  
Colin Farman ◽  
Nathan Cantley ◽  
...  
Keyword(s):  
Heart Disease ◽  
Cumulative Dose ◽  
Valvular Heart Disease ◽  
Current Evidence ◽  
High Dose ◽  
Weekly Dose ◽  
High Cumulative Dose ◽  
The Mean ◽  
Clinically Significant

Objectives: The indication for screening for valvular heart disease in patients taking cabergoline is based on evidence from patients with Parkinson’s disease on high-dose medication. However, current patients take much lower doses for indications such as hyperprolactinaemia disorders. Contemporary guidelines for echocardiogram monitoring in patients taking cabergoline are conflicting. This study aimed to review current clinical practice in our area regarding echocardiographic screening and to review the literature examining the evidence of valvular heart disease in patients taking lower dose cabergoline. Methods: This was a retrospective study of all patients with hyperprolactinaemia disorders prescribed cabergoline in a single UK NHS health board between January 2014 and July 2015. The proportion of patients receiving baseline and follow-up echocardiograms was recorded. A review of the published literature was carried out using the databases EMBASE and Medline to examine the current evidence for the effect cabergoline has on cardiac valves in patients treated for hyperprolactinaemia disorders. Results: The mean age was 51.7 ± 16.5 years with a 64.4% female predominance. The mean duration of therapy was 5.9 years ± 4.1 years. Of the total cohort ( n = 45), two (4.4%) patients had an initial baseline echocardiogram and five (13.2%) had follow-up echocardiograms every 24 months. Of the 25 articles identified, 12 showed no clinically significant evidence of valvular dysfunction in the cabergoline group groups. Of the remaining 13 articles, evidence for valvular changes was confined to high cumulative dose cabergoline patients and there was only one confirmed case of ‘cabergoline associated valvulopathy’ described. Conclusions: Clinically significant valvular dysfunction is uncommon and generally only reported in high cumulative dose treatment groups. We propose that clearer national guidelines are required and that echocardiogram screening be reserved for patients who are high risk, are taking a high weekly dose (≥2 mg cabergoline weekly) or high cumulative dose.

scholarly journals POS0677 THE ROLE OF MUSCULOSKELETAL ULTRASOUND IN PREDICTING THE RESPONSE TO JAK INHIBITORS: RESULTS FROM A LARGE MONOCENTRIC COHORT

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 583-583
Author(s):  
C. Garufi ◽  
F. Ceccarelli ◽  
F. R. Spinelli ◽  
S. Mancuso ◽  
C. Pirone ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Structural Damage ◽  
Power Doppler ◽  
Response To Treatment ◽  
Jak Inhibitors ◽  
Inflammatory Score ◽  
Inflammatory Status

Background:In the management of chronic arthritis, such as Rheumatoid Arthritis (RA), Ultrasound (US) assessment can provide relevant information about the joint inflammatory status in the diagnostic phase and even more in the monitoring of disease activity and structural damage1,2.Objectives:In this longitudinal study, we aimed to assesse the role of US in predicting the efficacy of JAK-inhibitors (JAKi) in RA patients.Methods:We enrolled RA patients starting baricitinib or tofacitinib. All patients were evaluated at baseline and after 4, 12, 24, 48 weeks. Disease activity was calculated by DAS28CRP. US examination in 22 joints (I–V MCPs and PIPs, wrists) aimed at evaluating inflammatory features (synovial effusion and hypertrophy, power Doppler-PD), through a semi-quantitative scale (0-3). The total US (0-198) and PD (0-66) scores were calculated. We scanned bilateral flexor (I–V fingers of hands) and extensor compartments (1-6) tendons: tenosynovitis was scored as absent/present (0/1), resulting in a total score (0-22).Results:We studied 102 patients (M/F 15/87; median age 59.2 years, IQR 17.75; median disease duration 144 months, IQR 126), 61 treated with baricitinib and 41 with tofacitinib. At baseline, the median total US score was 18 (IQR 19) and the median PD score 2 (4). We observed a significant reduction in both total and PD US scores at all time-points (p<0.0001) (Figure 1). At baseline, 75.4% of patients showed tenosynovitis involving at least one tendon, with a median score of 2 (IQR 3.5) significantly decreasing after 24 weeks (p=0.02). Multivariate analysis, adjusted for baseline DAS28CRP and other concomitant treatments (including glucocorticoids and methotrexate treatment), confirmed the independent association between baseline US (PD and tenosynovitis) scores and the reduction of disease activity at follow-up evaluations.Conclusion:The present study confirmed the early efficacy of JAKi in RA patients by using US evaluation. Furthermore, power doppler and tenosynovitis scores could play a predictive role in response to treatment.References:[1]MUELLER RB, HASLER C, POPP F, et al. Effectiveness, Tolerability, and Safety of Tofacitinib in Rheumatoid Arthritis: A Retrospective Analysis of Real-World Data from the St. Gallen and Aarau Cohorts. J Clin Med. 2019;8(10):1548.[2]COLEBATCH AN, EDWARDS CJ, ØSTERGAARD M, et al. EULAR recommendations for the use of imaging of the joints in the clinical management of rheumatoid arthritis. Ann Rheum Dis. 2013;72(6):804-14.Figure 1.Ultrasound inflammatory score (a) and Ultrasound Power Doppler (PD) score (b) at baseline and follow-up.Table 1.Baseline characteristics of 414 RA patients.WEEKS04122448US inflammatory score18 (19)11 (15.5)9.5 (11.7)7.5 (8)6 (11)US PD score2 (4)0 (2)0 (1)0 (1)0 (0.7)Disclosure of Interests:Cristina Garufi: None declared, Fulvia Ceccarelli: None declared, Francesca Romana Spinelli Speakers bureau: Abbvie, Eli Lilly, Consultant of: Gilead/Galapagos, Eli Lilly, Grant/research support from: Pfizer, Silvia Mancuso: None declared, Carmelo Pirone: None declared, Fabrizio Conti Speakers bureau: Abbvie, Eli Lilly, Sanofi, Pfizer, Consultant of: Gilead/Galapagos

Beta-Blockade in Intraseptal Anomalous Coronary Artery With Reversible Myocardial Ischemia

2021 ◽  
Vol 12 (1) ◽  
pp. 145-148
Author(s):  
Tam T. Doan ◽  
Athar M. Qureshi ◽  
Shagun Sachdeva ◽  
Cory V. Noel ◽  
Dana Reaves-O’Neal ◽  
...  
Keyword(s):  
Coronary Artery ◽  
Myocardial Ischemia ◽  
Dobutamine Stress ◽  
Medical Intervention ◽  
Beta Blockade ◽  
Fractional Flow ◽  
Flow Reserve ◽  
Reversible Ischemia ◽  
Improve Patient

Anomalous aortic origin of a left coronary artery (L-AAOCA) with an intraseptal course is a rare anomaly and can be associated with myocardial ischemia and sudden cardiac death. No surgical or medical intervention is known to improve patient outcomes. A 7-year-old boy with intraseptal L-AAOCA presented with nonexertional chest pain, syncope, and had reversible myocardial ischemia on provocative testing. The patient was started on β-blockade, following which his symptoms improved and resolved over a period of six years. A follow-up dobutamine stress magnetic resonance imaging no longer showed reversible ischemia, and cardiac catheterization with fractional flow reserve did not show coronary flow compromise.

Late anthracycline cardiotoxicity protection by dexrazoxane (ICRF-187) in pediatric patients: echocardiographic follow-up

2005 ◽  
Vol 14 (2) ◽  
pp. 128-136 ◽  
Author(s):  
Lubomir Elbl ◽  
Hana Hrstkova ◽  
Iva Tomaskova ◽  
Jaroslav Michalek
Keyword(s):  
Pediatric Patients ◽  
Anthracycline Cardiotoxicity

scholarly journals Physiological Evaluation of Anomalous Aortic Origin of a Coronary Artery Using Computed Tomography–Derived Fractional Flow Reserve

2021 ◽  
Author(s):  
Julien Adjedj ◽  
Fabien Hyafil ◽  
Xavier Halna du Fretay ◽  
Patrick Dupouy ◽  
Jean‐Michel Juliard ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Coronary Artery ◽  
Ct Angiography ◽  
Fractional Flow Reserve ◽  
Coronary Ct Angiography ◽  
Functional Evaluation ◽  
Fractional Flow ◽  
Coronary Ct ◽  
Flow Reserve

Background With the emergence of coronary computed tomography (CT) angiography, anomalous aortic origin of a coronary artery (ANOCOR) is more frequently diagnosed. Fractional flow reserve derived from CT (FFRCT) is a noninvasive functional test providing anatomical and functional evaluation of the overall coronary tree. These unique features of anatomical and functional evaluation derived from CT could help for the management of patients with ANOCOR. We aimed to retrospectively evaluate the physiological and clinical impact of FFRCT analysis in the ANOCOR registry population. Methods and Results The ANOCOR registry included patients with ANOCOR detected during invasive coronary angiography or coronary CT angiography between January 2010 and January 2013, with a planned 5‐year follow‐up. We retrospectively performed FFRCT analysis in patients with coronary CT angiography of adequate quality. Follow‐up was performed with a clinical composite end point (cardiac death, myocardial infarction, and unplanned revascularization). We obtained successful FFRCT analyses and 5‐year clinical follow‐up in 54 patients (average age, 60±13 years). Thirty‐eight (70%) patients had conservative treatment, and 16 (30%) patients had coronary revascularization after coronary CT angiography. The presence of an ANOCOR course was associated with a moderate reduction of FFRCT value from 1.0 at the ostium to 0.90±0.10 downstream the ectopic course and 0.82±0.11 distally. No significant difference in FFRCT values was identified between at‐risk and not at‐risk ANOCOR. After a 5‐year follow‐up, only one unplanned percutaneous revascularization was reported. Conclusions The presence of ANOCOR was associated with a moderate hemodynamic decrease of FFRCT values and associated with a low risk of cardiovascular events after a 5‐year follow‐up in this middle‐aged population.

scholarly journals Long-Term Safety and Efficacy of Subcutaneous Cladribine Used in Increased Dosage in Patients with Relapsing Multiple Sclerosis: 20-Year Observational Study

2021 ◽  
Vol 10 (21) ◽  
pp. 5207
Author(s):  
Konrad Rejdak ◽  
Adriana Zasybska ◽  
Aleksandra Pietruczuk ◽  
Dariusz Baranowski ◽  
Sebastian Szklener ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Cumulative Dose ◽  
Induction Dose ◽  
Disability Status ◽  
Risk Of Progression ◽  
Dosing Regimens ◽  
Favorable Safety ◽  
Relapsing Multiple Sclerosis

Cladribine is currently registered as a 10-milligram tablet formulation with a fixed cumulative dosage of 3.5 mg/kg over 2 years. It is important to investigate if an increased dosage may lead to further clinical stability with preserved safety. This study used an off-label subcutaneous (s.c.) formulation of cladribine and compared outcomes (Expanded Disability Status Scale (EDSS) scores and disease progression) between 52 relapsing multiple sclerosis (RMS) patients receiving different s.c. dosing regimens with up to 20 years of follow-up. The study group received induction therapy with s.c. cladribine (1.8 mg/kg cumulative dose; consistent with 3.5 mg/kg of cladribine tablets). Patients were subsequently offered maintenance therapy (repeated courses of 0.3 mg/kg s.c. cladribine during 5–20-year follow-up). Forty-one patients received an increased cumulative dose (higher than the induction dose of 1.8 mg/kg); 11 received the standard induction dose. Risk of progression on the EDSS correlated with lower cumulative dose (p < 0.05) and more advanced disability at treatment initiation (p < 0.05) as assessed by EDSS change between year 1 and years 5 and 10 as the last follow-up. Maintenance treatment was safe and well-tolerated, based on limited source data. Subcutaneous cladribine with increased cumulative maintenance dosage was associated with disease stability and favorable safety over a prolonged period of follow-up (up to 20 years) in RMS patients.

scholarly journals Cyclosporine in the treatment of idiopathic nephrosis.

1994 ◽  
Vol 5 (4) ◽  
pp. 1049-1056
Author(s):  
P Niaudet ◽  
R Habib
Keyword(s):  
Structural Damage ◽  
Therapeutic Effects ◽  
Steroid Resistant ◽  
The Past ◽  
Cyclosporine Nephrotoxicity ◽  
Steroid Sensitive ◽  
Idiopathic Nephrosis ◽  
High Doses ◽  
Functional Toxicity

Within the past decade, there have been numerous reports on the use of cyclosporine in idiopathic nephrosis. In this review, the results of both uncontrolled and controlled studies of the therapeutic effects of cyclosporine in steroid-sensitive/dependent idiopathic nephrosis and in steroid-resistant idiopathic nephrosis are analyzed. Cyclosporine is efficient in up to 80% of patients with steroid-sensitive/dependent idiopathic nephrosis. Most patients, however, relapse when the drug is withdrawn, thus necessitating prolonged treatments. Although cyclosporine is less efficient in patients with steroid-resistant idiopathic nephrosis, a few studies seem to indicate that this drug may be successful in some patients, especially if combined with corticosteroids. There is no evidence that cyclosporine can prevent the recurrence of nephrotic syndrome on the graft after renal transplantation. However, in patients in whom disease has recurred, high doses of cyclosporine may be effective alone or in combination with plasma exchanges. The main worrisome side effect of cyclosporine is chronic nephrotoxicity, which should be differentiated from acute or "functional" toxicity. Follow-up studies including pretreatment and posttreatment renal biopsies show a lack of correlation between structural damage and renal function, suggesting that a histologic examination of the renal parenchyma is the only reliable way of evaluating chronic cyclosporine nephrotoxicity.

Abstract 2344: Cumulative Radiation Dose Estimate From Medical Testing in Grown-Up Patients With Congenital Heart Disease

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Lamia Ait-Ali ◽  
Nicoletta Botto ◽  
Maria Grazia Andreassi ◽  
Pierluigi Festa ◽  
Eugenio Picano
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Effective Dose ◽  
Cumulative Dose ◽  
Congenital Heart ◽  
Cumulative Exposure ◽  
X Rays ◽  
Dose Estimate ◽  
Risk Of Cancer ◽  
Beir Vii

Background: The “Biological effects of Ionizing Radiation” (BEIR VII,2005) underlines “the need of studies of infants who are exposed to diagnostic radiation”. Aim: to assess the individual cumulative lifetime radiological dose in grown up congenital heart disease (GUCH) patients. Methods: In 41 consecutive operated GUCH patient (24 males, age= 27 ± 9 years old), followed in our outpatient clinic, a cumulative radiological history was collected with a structured questionnaire and access to lifetime hospital records. All patient underwent at least one surgical intervention during the infancy for Tetralogy of Fallot (n=18), aortic coarctation (n=10), anatomical/functional univentricular heart (n=8), other congenital heart disease (n=5) The cumulative exposure was expressed in milliSievert (mSv) and derived from average effective dose estimates of individual examinations proposed by the European Commission Medical Imaging Guidelines (2001). The attributable cancer risk was estimated from BEIR VII, 2005 document. Results: On average, cumulative dose estimate was 22.3 ± 12.4 (mean ± SD) mSv per patient, equivalent to about 1115 ± 620 chest x-rays. Diagnostic and interventional catheterization accounted for the most important sources of exposure (see figure ). The median cumulative dose gave an average extra-risk of cancer of about 1 out of 200 patients (range, 1 in 448 to 1 out of 58). Conclusion: the average contemporary GUCH patient is exposed to a significant cumulative radiological effective dose. Every effort should be done to justify the indications and to optimise dose delivery during ionizing testing.

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