Abstract We report the case of a 48–year–old female with a special history of ischemic heart disease. It started in 2021 with an acute anterior ST myocardial infarction: the coronary angiography showed subocclusive stenosis at the first tract of the left anterior descending (LAD), without other coronary stenoses. The patient was treated with primary PCI + DES; the echocardiogram showed EF 30% and akinesia of apex, intermediate segments of anterior wall and interventricular septum. During the same hospitalization the patient experienced recurrence of angina with transient ST elevation in the anterior and inferior leads; a control coronary angiography was unchanged. She was started on therapy with nitrates and diltiazem up to the tolerated dose, statin as well as antiplatelet and anticoagulant therapy due to apical thrombus. She underwent ICD implantation in primary prevention in January 2022. During 2022, there were several accesses to the ED for vasospastic angina despite medical therapy at the maximum tolerated dose. In October 2023 the patient experienced an acute chest pain followed by cardiac arrest, pulseless electrical activity and acute cardiogenic shock. After resuscitation procedures, she underwent an emergency coronary angiography which showed excellent result of the previous PCI, as well as stenosis of the distal edge of the stent resolving after injection of i.c. nitrates. No arrhythmic events at ICD recording and continuous electrocardiographic monitoring in ICU were observed. Cardiac MRI showed areas of subendocardial LGE involving the apex, anterior, anterolateral and septal segments due to ischemic scar; we also observed areas of edema and LGE with an ischemic pattern at the infero–septal and inferior wall in toto, suggesting recent ischemia; EF was 31%. During hospitalization the patient experienced episodes of typical angina with poor response to medical therapy at the maximum tolerated dose. The current clinical case most likely points to acute myocardial infarction due to vasospasm of the right coronary artery with acute pump failure resulting in cardiac arrest and no specific recommendations exist in recent cardiologic guidelines on the strategy to adopt for this acute clinical setting. In the hypothesis of a vasospastic pathogenesis of the problem, counseling for modulation of the stellate ganglion was requested.

Background: β-thalassemia major (TM) is characterized by a wide spectrum of clinical manifestations and laboratory findings and the disease phenotype largely depends on the underlying mutations of the β gene. These mutations cause a reduced (β+) or absent (β0) production of the β-globin chain. No study has evaluated the link between genotype and pancreatic iron, representing a powerful predictor for glucose metabolism and cardiac iron and complications. Aims: The objective of this multicenter study was to evaluate the impact of genotype on pancreatic iron levels and glucose metabolism in TM. Methods: We considered 549 TM patients (36.23±10.63 years, 46.3% females), consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia Network. T2* measurements were performed over pancreatic head, body and tail and global value was the mean. The pattern of disturbances of glucose metabolism was assessed by means of the oral glucose tolerance test (OGTT). Results: Three groups of patients were identified: homozygous β+ (N=158), compound heterozygous β0β+ (N=206), and homozygous β0 (N=145). The three groups were homogeneous for age, sex, age at start of regular transfusions and chelation, and frequency of splenectomy. The homozygous β0 group showed significantly lower global pancreas T2* values than the homozygous β+ group (9.91±8.13 ms vs 14.45±10.72 ms; P<0.0001) and the heterozygous β0β+ group (9.91±8.13 ms vs 14.69±10.76 ms; P<0.0001). Pancreatic iron overload (T2*<26 ms) was found in 81.6% of β+β+ patients, 82.5% of β0β+ patients, and 95.1% of β0β0 patients (P<0.0001) (Figure 1A). β0β0 patients were more likely to have pancreatic iron overload than both β+β+ patients (odds ratio-OR=4.39, 95%CI=2.01-9.61; P<0.0001) and β0β+patients (OR=4.14, 95%CI=1.94-8.86; P<0.0001). An altered OGTT was found in 154 patients (34 impaired fasting glucose, 54 impaired glucose tolerance, and 66 diabetes mellitus), all showing pancreatic iron overload. The prevalence of impaired OGTT was significantly higher in the homozygous β0 group than in the homozygous β+ group (34.9 vs 22.4%; P=0.042) (Figure 1B). β0β0 patients had around twice the risk of alterations of glucose metabolism (OR=1.86, 95%CI=1.33-3.07; P=0.014) than β+β+ patients. Image:Summary/Conclusion: In TM the homozygous β0 genotype is associated with higher pancreatic iron levels and prevalence of impaired glucose metabolism. Therefore, the knowledge of the genotype can be useful in the prediction of some phenotypic features and in the clinical and instrumental management of TM patients.

Abstract Funding Acknowledgements Type of funding sources: Private company. Main funding source(s): The MIOT project receives “no-profit support” from industrial sponsorships (Chiesi Farmaceutici S.p.A., ApoPharma Inc.). Background. Sickle β-thalassemia (Sβ-thal) is a hereditary hemoglobinopathy resulting from the combined heterozygosity for sickle cell and β-thalassemia genes. Cardiac involvement in Sβ-thal patients has been poorly investigated. Aim. We aimed to evaluate myocardial iron overload and cardiac function by cardiovascular magnetic resonance (CMR) in patients with Sβ-thal. Methods. One hundred and eleven Sβ-thal patients consecutively enrolled in the Myocardial Iron Overload in Thalassemia (MIOT) network were studied and compared with 46 sickle cell disease (SCD) patients. Biatrial and biventricular function CMR parameters of Sβ-thal patients were compared with those of 111 healthy volunteers, matched by gender and age. Myocardial iron overload (MIO) was assessed by T2* technique. Cine images were acquired to quantify biventricular function. Macroscopic myocardial fibrosis was evaluated by late gadolinium enhancement (LGE) technique. Results. In Sβ-thal and SCD patients morphological and functional MR parameters were not significantly different, except for left atrial area and SVI (p = 0.023 and p = 0.048, respectively) that were significantly higher in SCD patients. No significant differences between the two groups were found in terms of myocardial iron overload and macroscopic myocardial fibrosis. When compared to healthy subjects, Sβ-thal patients showed significantly higher bi-atrial and biventricular parameters except for LVEF that was significantly lower (Fig.1). Conclusions. The CMR analysis confirmed that Sβ-thal and SCD patients are phenotypically similar. Since Sβ-thal patients showed markedly different morphological and functional indices from healthy subjects, it would be useful to identify Sβ-thal/SCD-specific bi-atrial and biventricular reference values.

Background:Patients with non‐transfusion dependent thalassaemia (NTDT) can be placed on regular transfusional therapy either for the prevention or for the management of different complications.Aims:We retrospectively evaluated the effects of blood transfusions (BT) in the real‐life and quite extensive context of the Myocardial Iron Overload in Thalassaemia (MIOT) network where most of biochemical, cardiac, hepatic parameters and morbidities typical of the NTDT patients could be analysed and compared in a chronologically manner.Methods:147 NTDT patients (46.49 ± 12.27 years; 92 females) who started regular BT at the mean age of 21.84 ± 17.85 years were considered. Magnetic Resonance Imaging (MRI) was used to quantify iron overload (T2∗ technique) and biventricular morphological and functional parameters (cine sequences).Results:For the 40% of the patients there were more than two indications for the transition to regular BT, with anemia being present in the 92.5% of the cases. The patients reached a pre‐transfusion hemoglobin of 9.64 ± 0.72 g/dl.The percentage of chelated patients increased significantly after starting regular BT (52.5% vs 91.7%; P < 0.00001).Table 1 shows the changes (6 months before vs 6 months after starting regular BT) in the haematochemical and iron‐overload parameters. A down‐regulation of all erythropoietic and/or haemolysis indices and a drop‐in platelets and white blood cell count were detected. No changes in serum ferritin, MRI liver iron concentration (LIC) and global heart T2∗ values were detected.There was a significant decrease of the left ventricular end‐diastolic volume index (101.58 ± 19.67 ml/m2 vs 91.65 ± 20.99; P = 0.050).After the start of regular BT, patients were followed‐up for 24.08 ± 15.62 years. There was a significant increase in the frequency of endocrinopathies (diabetes, hypogonadism, hypothyroidism and osteopenia), bone pain, infections, and alloimunization, but their prevalence remained lower than 20%.A positive impact on patients’ health‐related quality of life was detected, with the sense of well‐being passing from 16.4% to 73.0% (P < 0.0001).Summary/Conclusion:Following the use of regular BT and chelation therapy, only a mild increase in most of the complications evaluated in the analysis was recorded; we cannot exclude that it could be ascribable to aging per se, as it happens for general population. No increase in iron overload parameters was detected and conversely, we recorded a positive cardiac remodelling. Therefore, in the Italian context, the decision to regularly transfuse patients with NTDT, despite sometimes complex and problematic, may represent a way to prevent or slow down the natural progression of the disease and improve the patients overall quality of life.image

In non transfusion dependent thalassemia (NTDT) the lack of a clear genotype-phenotype relationship complicates the already complex and extensive scenario in clinical practice. Our aim was to detect if the presence of a β°/β° homozygous genotype was associated to different rate of cardiac findings by Cardiovascular Magnetic Resonance (CMR) and cardiac complications. We considered 81 patients with thalassemia intermedia never transfused o who received occasional transfusions (37.7±11.4 years, 39 females) consecutively enrolled in the Myocardial Iron Overload in Thalassemia project. CMR was used to quantify iron overload (T2* technique), biventricular morphological and functional parameters (cine sequences), and the presence of myocardial fibrosis (late gadolinium enhancement-LGE technique). All cardiac complications were classified according to international guidelines. Two groups of patients were identified: non homozygous β°/β° genotype (N=61) and homozygous β°/β° genotype (N=20.) No significant differences for sex and age were found between the groups. Patients with homozygous β°/β° genotype had lower mean haemoglobin levels (8.6±1.1g/dl vs 9.2±1.2 g/dl) but the difference did not reach the statistical significance (P=0.060). No patient showed cardiac iron and global heart T2* values were comparable between the two groups. Left atrial area index, left ventricular (LV) end-diastolic, end-systolic and stroke volume indexes, LV mass index, right ventricular end-diastolic and end-systolic volume indexes were significantly higher in the homozygous β°/β° group (see Table). Frequencies of heart failure and arrhythmias were comparable between the groups. Non-β0/β0 homozygous genotype β0/β0 homozygous genotype P Left Atrial Area (cm2/m2) 13.87±2.59 16.63±2.59 0.001 LV EDVI (ml/m2) 94.88±15.59 112.94±21.52 0.003 LV ESVI (ml/m2) 35.22±9.55 41.88±9.70 0.018 LV SVI (ml/m2) 61.98±12.57 69.81±11.20 0.029 LV mass index (g/m2) 61.26±10.15 68.63±15.89 0.030 RV EDVI (ml/m2) 91.27±23.50 107.53±23.87 0.019 RV ESVI (ml/m2) 33.93±17.55 40.81±15.20 0.043 Heart remodelling related to a high cardiac output state cardiomyopathy was more pronounced in patients with homozygous β°/β° genotype. These data can support the knowledge of different phenotypic groups in the management of NTDT patients.