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A 73 year–old man was referred by his general practitioner to our ambulatory for worsening dyspnea. He also reported substantial weight loss (almost 20 kg during the last three months), new onset dysphonia and dry cough. The patient’s medical history also included a former tobacco addiction, arterial hypertension and dyslipidemia. There was not history of cardiomiopathy. Electrocardiogram, showed: sinus rhythm, 60/min with inferior and anterior–lateral abnormality of repolarization. No laboratory exams were available at the first visit. An echocardiogram was performed, showing: marked septal hypertrophy (IVSd= 23 mm), septal hypokinesia, with an ejection fraction at lower limits of normality (EF= 54%), neither systolic anterior motion of the mitral valve. Minimal pericardial effusion was seen. We required a CT scan of the chest, that showed a large (5x8x11cm) mass in the left upper lobe with ipsilateral mediastinal lymphadenopathy. The mass directly extended into the mediastinum with infiltration of pericardial leaflet, left atrium and the left wall of the aortic arch. A hypodense formation of approximately 4 cm in the interventricular septum in the apical portion was reported. PET–CT with FDG was performed, which documented hypercaptation of the radioactive tracer at the level of the above–mentioned lesions. The patient underwent fine–needle aspiration biopsy of the lung mass and the histological examination led to the diagnosis of squamous cell carcinoma of the lung. Systemic treatment with carboplatin plus placlitaxel and pembrolizumab was subsequently started. A cardiac CMR was performed, which documented an area of 30x17x31 mm located at the septal (mid–apical portion), apex and parapical portion of the free wall of the right ventricle with transmural extension. At this area, extensive late gadolinium enanchement (LGE) at marginal level with a central non–capillary core and hyperintense in T2 sequences (compatible with central necrotic lesion). The pericardium also showed LGE and a mild pericardial effusion (maximum 8 mm); left atrium involvement, seen on CT, was not documented . After he completed the third cycle of CHT, at 5 months from the diagnosis, the echocardiogram showed a substantial disappearance of the mass infiltrating the interventricular septum without evidence of pericardial effusion. The ecg was substantially unchanged. The patient stopped carboplatin and paclitaxel after 3 cycles and kept maintenance pembrolizumab still ongoing.

A 75–year–old overweight man, affected by hypertension, diabetes mellitus and atrial fibrillation since 2020. After 3 unsuccessful attempts of electrical cardioversion it was opted for a strategy of rate control with beta blocker and anticoagulant therapy with Rivaroxaban 20 mg. Following episodes of rectal bleeding; adenocarcinoma of the colon was diagnosed. The patient underwent hemicolectomy and started therapy with Pembrolizumab. The anticoagulant was replaced with Edoxaban 60 mg. In August 2022, he was admitted to the emergency department for severe signs and symptoms of heart failure. On ECG, atrial fibrillation with a heart rate of 90 bpm and non–specific changes in ventricular repolarization. The echocardiogram showed a severe reduction of the ejection fraction (FE 30%), which was not present at previous controls. On blood tests, troponins were negative and BNP increased. The patient underwent coronarography which was negative for significant lesions, and heart failure therapy was prescribed. Three months later the patient came to our cardio–oncology outpatient clinic; we repeated the echocardiogram which showed a recovery of the ejection fraction to 45% and planned a cardiac MRI. Cardiac MRI (CMR) showed global left ventricular hypokinesia (FE 42%) and late subepicardial gadoline enhancement in the basal segment of the inferior wall and transmural in the basal segment of the lateral wall without signs of oedema. Report described as compatible with myocarditis. The case was discussed collegially with radiologists and oncologists, and it was decided to discontinue immunotherapy (ICI). Myocarditis is the most common cardiovascular adverse events of ICI therapy, although it has a very low incidence. Generally, myocarditis related to ICI therapy has a high mortality rate and requires discontinuation of ICI. In addition, CMR may have a lower sensitivity in this setting. There is also a possibility of developing left ventricular dysfunction without associated myocarditis in the absence of increase in cardiac troponin and active myocardial inflammation at CMR. Although our case has been defined as myocarditis, it presents some unclear aspects due in part to the early non–diagnosis as a complication of ICI therapy. Although cancer patients taking ICI has expanded considerably in recent years, the evidence on cardiovascular complications is scarce and unknown to the clinical cardiologist.

Background Radiation therapy (RT) is widely diffused in the treatment of cancer; but it could lead to various negative consequences on the cardiovascular system, even several years after treatment end. They include also valvular heart diseases, arrythmias, coronary artery diseases, heart failure, pericardial diseases, systemic and pulmonary artery diseases. We report an interesting case about RT cardiotoxicity different manifestation occurred in the same patient. Case report: 79 years old patient, history of previous testicular seminoma when he was 54 years old (1997), treated through surgery and RT with betatron (total body cobalt). In 2008 aortic valve replacement with mechanical prothesis; in 2017 first hospitalization for heart failure during atrial fibrillation. In subsequent years, recurring episodes of atrial fibrillation (2 unsuccessful attempts at electrical cardioversion), and heart failure exacerbations with mild reduced ejection fraction, treated through medical therapy improvement. At follow–up echocardiogram (03/19) finding of ejection fraction mild reduced (45%), right sections increased in volumes, tricuspid valve moderate regurgitation. In January 2022, at the last cardiac check–up, he reported worsening dyspnoeic symptoms, and occasional episodes of retrosternal pain in last months. It was performed Coro–TC observing a 60% stenosis at distal tract of right coronary; in addition, patient underwent a transoesophageal echocardiogram which documented further reduction in left ventricle ejection fraction, and worsening tricuspid regurgitation to a severe degree, with anulus dilatation and partial failure of leaflets coaptation, which appeared fibro–elastic; inferior vena cava ectasia, Paps 40–45 mmHg circa. Holter–ECG showed atrial fibrillation for all 24 hours, plus 2000 BEV. The case was discussed in Heart Team, and an indication was placed for Triclip intervention. Discussion Nowadays great achievements of anticancer therapies improved patients’ survival, consequently increased the number of anticancer therapies complications; therefore, an accurate cardiac screening for early diagnosis and effective treatment of CV adverse effects is necessary. Several distinct factors contribute to determine the onset cardiotoxicity insurgence, such as the type of cancer, its anatomical localization; radiation techniques applied, total and fractional radiation doses; patient’s age and his comorbidity and risk factors for cardiovascular diseases.

Anthracyclines represent the most effective chemotherapeutic agent in the treatment of non–Hodgkin‘s lymphoma (NHL), although their use is limited due to the risk of cardiac toxicity. This occurs mainly in elderly patients, those with a history of cardiovascular (CV) disease and/or multiple concomitant risk factors. Liposomal doxorubicin has been shown to reduce this toxicity. The aim of this retrospective study is to investigate the use of non–pegylated liposomal doxorubicin in high–risk patients in terms of haematological response rate and CV events. In a single centre, 15 patients undergoing R–COMP regimen (Rituximab, Prednisone, Cyclophosphamide, Vincristine, Myocet liposomal doxorubicin) were consecutively collected from January 2020 to December 2021. The mean age of patients was 73.9 years and 60% were male. The baseline mean left ventricular ejection fraction (LVEF) was 55.9%; four patients had a baseline FE of Conclusions Our results support the efficacy and safety of R–COMP in a population at high risk for cardiac events, otherwise excluded from anthracycline–containing therapy. Liposomal formulatio reduces doxorubicin cardiomyocyte accumulation and thus toxicity, providing the best possible treatment for the majority of the onco–haematological population.

39–year–old female, without cardiovascular risk factors. At the end of pregnancy she complained of progressive dyspnoea and so she was admitted to the emergency room. Blood tests showed elevated D–dimer and LDH values. A chest CT scan was performed showing a mediastinal mass of about 15 cm encompassing the ascending aorta, the left brachiocephalic trunk and the superior vena cava, both of which appeared thrombosed. Therapy with low molecular weight heparin was started. The patient underwent a mediastinal biopsy, which documented a primary mediastinal non–Hodgkin‘s lymphoma. The baseline cardiological evaluation showed a preserved ejection fraction (60%) at echocardiogram (ECHO). The first cycle of chemotherapy with R–CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine) was started. After an episode of hypoesthesia of the left upper limb, that regressed spontaneously within a few hours, she performed MRI that showed multiple areolas compatible with ischemic disease. Following these results the patient was submitted to an ECHO with saline solution injected through the right brachial vein that documented evidence of early opacification of the left atrium and subsequent opacification of the right sections (after 3 cardiac cycles) (Fig. 1–2). This finding suggested a right–to–left shunting, via the bronchial lower district to the left atrium (pulmonary veins). This suspicion was confirmed by CT angiography, which showed occlusion of the superior vena cava with passage of contrast into azygos and early opacification of peribronchial venous circles (Fig. 3). A patency of foramen ovale was ruled out by injection of saline solution through the femoral vein. After the second cycle of chemotherapy, ECHO showed diffuse hypokinesia and reduced EF to 50%. It was then decided to proceed with the third cycle according to the intensified R–DAEPOCH scheme, except for doxorubicin, because of the cardiotoxicity developed by the patient. A cardioprotective therapy was also started with bisoprolol and ramipril with rapid titration. At subsequent radiological controls, a progressive reduction of the mediastinal mass was found and after just one month, the echocardiogram showed a complete recovery of the EF. Contrast injection confirmed presence of a veno–venous shunt. Cardio–oncology is an intriguing and complex discipline that requires the development of local multidisciplinary teams for challenging situations that patients with cancer may ask us to address.

A 53–year–old woman was admitted for chest pain for over two weeks, fever, dry cough, fatigue and myalgia. Chest pain increased in supine position and inspiration. Nasopharyngeal swab was positive for SARS–CoV–2 RT–PCR assay. Admission ECG displayed mild ST–segment elevation (0,5 mm) in inferolateral leads and echocardiogram showed normal left ventricular volume, mildly decreased left ventricular EF (52%) and no regional wall motion abnormalities. Blood tests exhibited elevated values of high–sensitivity troponin I (818 pg/mL), proBNP (19.190 pg/mL), CRP (42 mg/dL), D–Dimer test (1090 ng/mL) and WBC (13000/uL, N 89%, L 7%). IL–6 resulted slightly increased (18 ng/mL). ECG after 24 hours showed T wave inversion in inferolateral leads. Coronary CT angiography revealed normal epicardial arteries. A new echocardiogram, after five days, showed infero–basal hypokinesia, improved global EF (57%) and minimal pericardial effusion. Aspirin and fondaparinoux were started. Myopericarditis was suspected and high dose steroids were administered. After a few days, symptoms improved and ECG, echocardiographic abnormalities and troponin levels were normalized. At 6 weeks follow–up the patient was asymptomatic, ECG and echocardiogram were both normal. Instead cardiac MRI showed signs of endothelial injury: presence of interstitial oedema in the inferoapical and anteroseptal wall (STIR–T2–weighted), without late gadolinium enhancement. We measured blood levels of endothelial dysfunction markers: soluble ICAM–1, VCAM–1 and von Willebrand factor (vWF). They all resulted elevated as compared to a laboratory pool of normal serum (535 ng/ml, 265 ng/ml, and 1659 ng/ml, respectively). Our case was suggestive of myopericarditis related to Sars–Cov–2, but echocardiogram and MRI did not show signs of myocarditis permanent damage. However MRI showed interstitial oedema and hyperemia, typical signs of endothelial injury. Moreover we found high levels of soluble endothelial adhesion molecules, vWF, ICAM–1 and VCAM–1, likely expression of the microcirculatory endothelial dysfunction due to myocardial endothelialitis. In conclusion, our case report suggests that, in COVID–19, acute myocardial injury associated with clinical and investigational signs of myocarditis can be due to myocardial endothelialitis rather than true myocarditis and that an early management with anti–inflammatory drugs (steroids) can be particularly beneficial in patients with unexplained elevated cardiac troponin.

Background and Purpose The capability of transcranial Doppler sonography (TCD) to detect a patent foramen ovale (PFO) has been established. However, which provocative maneuver and what timing of contrast injection are most effective to induce a right-to-left shunt has not yet been determined. Methods We selected 38 cerebrovascular patients (21 men, 17 women) with positive contrast study for PFO on transesophageal echocardiography. Patients underwent a TCD with bilateral monitoring of the middle cerebral arteries (MCAs) and injection of a contrast solution. The injection was repeated (1) during normal breathing (basal conditions); (2) before Valsalva maneuver (VM); (3) during VM; (4) immediately after VM; and (5) during cough. The latency time and the total number of microbubbles for each side were recorded. Results TCD found positive results for PFO in 30 patients. Twenty were positive even during basal conditions. The number of positive cases varied according to the timing of the VM in relation to the contrast injection: 28, 25, and 27 cases were positive when the injection was performed before, during, and after VM, respectively, while 26 were positive during cough. There were significant differences in the number of microbubbles in the MCAs between the procedures ( P P Conclusions The injection performed before VM appeared to be the most effective TCD procedure in determining the transit of microbubbles through a PFO and subsequently in the MCAs.

Right atrial (RA) mapping has been recently more carefully examined in patients with idiopathic atrial fibrillation (AF) in order to improve radiofrequency (RF) catheter-mediated ablation lines to control recurrences. The aim of this study was to map right atrial activation during AF to analyze relationship between anatomy and atrial activation for specific sites. Twenty-four patients with recurrent, drug-refractory, paroxysmal AF underwent an extensive mapping of the RA before attempting RF linear lesion catheter ablation. A typical pattern of atrial activation was recorded in all patients which was consistent with a more regular activity on the trabeculated right atrium (type I AF) and a more fragmented and complex activation on the posterior and the anterior septum (type II and III AF). This paper helps to understand the influence of the anatomic barriers to atrial activation during atrial fibrillation.

The simple determination of transaortic pressure gradient does not accurately assess the severity of an aortic valve stenosis. Thus, estimating the aortic valve area (AVA) is vital for clinical decision-making. Cardiac catheterization has been considered the "gold-standard" for the quantification of the stenotic valve area, but this technique may underestimate the actual valve area when aortic regurgitation is associated. Doppler transthoracic echocardiography (TTE) with the continuity equation method is usually employed for AVA estimation. Recently, in pure aortic stenosis, transesophageal echocardiography (TEE) has provided AVA values well-correlated to hemodynamic invasive results.In this study, we correlated AVA values by TTE and multiplane TEE in 18 patients with combined aortic valve stenosis and regurgitation.The mean values of AVA by TEE and TTE were 0.74 +/- 0.12 and 0.68 +/- 0.55 cm2, respectively (p = NS). TEE-derived AVA correlated well to TTE-derived AVA (r = 0.816; p0.0001). Critical aortic stenosis was predicted by TEE with 100% sensitivity and specificity. Total time of examination was significantly longer for TTE (p0.00001).In conclusion, direct planimetry by multiplane TEE is a reliable method for AVA determination in aortic stenoinsufficiency. For this purpose, when the technical quality of TTE study is poor or when the patient is critically ill and does not tolerate a longer lasting TTE, multiplane TEE should be considered.

Transesophageal echocardiography (TEE) is useful in the assessment of potential cardiac sources of emboli in patients with ischemic stroke and clinical history of heart disease. Aim of our study was to assess the utility of TEE in stroke patients with and without clinical evidence of cardiac disease. In addition, we evaluated if multiplane TEE, versus mono and biplane TEE, provides additional information about potential cardiac sources of emboli. A total of 89 ischemic stroke patients were studied: 30 patients with a history and clinical evidence of cardiac disease (Group A) and 59 patients without evidence of cardiac disease (Group B). All patients had a documented ischemic lesion of the brain. Patients who had an extracardiac potential source of emboli were excluded from the study. In all patients, transthoracic (TTE) and biplane TEE were performed, whereas omniplane TEE was performed in 40 patients only. In Group A, sources of emboli were disclosed by TTE in 33% of the patients. When TEE was performed the percentage of positive cases raised to 83% (p0.001). In Group B, TTE was positive in only 10% of the patients as opposed to 43% with TEE (p0.001). Omniplane TEE revealed a potential source of emboli in 23 out of 40 (57%) patients versus 16/40 (40%) and 20/40 (50%) with monoplane and biplane, respectively. TEE is useful in patients with cardiovascular disease in whom clinical evaluation and TTE are negative for sources of emboli. TEE is of great value in stroke patients without clinical evidence of cardiovascular disease in whom an extracardiac potential source of emboli has been excluded.(ABSTRACT TRUNCATED AT 250 WORDS)

It is known that chronic alcoholism causes morphological changes of the myocardium before the development of a specific dilated cardiomyopathy. We studied a group of chronic alcoholics, with normal arterial pressure and without clinical evidence of liver cirrhosis, to evaluate left ventricular function, both before and after withdrawal of ethanol. A M-B mode echo recording of the left ventricle and left ventricular inflow Doppler velocimetry with carotid pulse tracing was performed in each patient within 24 hours of the last alcohol consumption and after a period of abstinence at least 3 weeks. We analysed parameters of left ventricular systolic and diastolic functions, in comparison with a group of normal subjects well matched for age, body surface area and heart rate. The results showed that, in the group of alcoholics, a cardiac hypertrophy exists with increased left ventricular mass and normal parameters of left systolic ventricular function, but with altered ratio PEP/LVET. This last result is the consequence of an abnormal left diastolic ventricular function, as demonstrated from the analysis of the Doppler indexes of left ventricular filling (lower ratio E/A). Left ventricular inflow Doppler velocimetry showed different results in alcoholics and control subjects in the early diastolic flow velocity peak (61 +/- 12 vs 84 +/- 8) and in the peak flow velocity in the atrial contraction phase (62 +/- 10 vs 40 +/- 5.6). We have not observed any change of the echocardiographic parameters after the short period of alcohol withdrawal. We advance the hypothesis that there is an altered diastolic function depending, not only on the hypertrophy of the myocardium, but also on the myocardial interstitial involvement caused by ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)