Mitro-aortic fibrosa pseudoaneurysm and concomitant aortic stenosis: How to kill two birds with a stone.

Pseudoaneurysm of mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare acquired malformation of the mitral-aortic intervalvular area. It appears as a pulsatile cavity in the mitral-aortic junction communicating with the left ventricular outflow tract. P-MAIVF has been reported as a complication of aortic and mitral valve surgery, infective endocarditis, and thoracic trauma. It is associated with life-threatening complications. The recommended treatment is surgery, however, conservative therapy is an alternative approach for high-risk patients or when surgical treatment is refused. We describe a successfully exclusion of a P-MAIVF by transapical transcatheter aortic valve implantation in a patient with concomitant severe aortic stenosis.

Efficacy and safety of deferiprone for the treatment of superficial siderosis: results from a long-term observational study.

BACKGROUND: Superficial siderosis (SS) of the central nervous system is a rare and heterogeneous condition due to deposition of hemosiderin on the surface of the brain and spinal cord. The usually progressive clinical course is characterized by a combination of hearing loss, cerebellar ataxia, and myelopathy. There is no known treatment for SS, but the iron chelator deferiprone (DFP) has been proposed as a potentially useful treatment. METHODS: We present a long-term (average 3.7 years) evaluation of four cases of SS treated with DFP (15 mg/kg po bid). RESULTS: Treatment with DFP proved safe and well tolerated. Two out of the four subjects were unchanged while the other two presented a clinical improvement with reduction of postural instability and cerebellar signs. Blinded evaluation of magnetic resonance imaging (performed every 6 months during follow-up) showed a reduction of the abnormal iron deposition for all patients. CONCLUSIONS: This long-term observational study suggests that DFP may be effective in the management of the neurological manifestations associated with iron accumulation in SS. CLINICALTRIALS. GOV IDENTIFIER: NTC00907283.

Calibration of myocardial T2 and T1 against iron concentration.

BACKGROUND: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron. METHODS: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading. Ex-vivo R1 and R2 measurements (R1=1/T1 and R2=1/T2) at 1.5 Tesla were compared with myocardial iron concentration measured using inductively coupled plasma atomic emission spectroscopy. RESULTS: From a single myocardial slice in formalin which was repeatedly examined, a modest decrease in T2 was observed with time, from mean (± SD) 23.7 ± 0.93 ms at baseline (13 days after death and formalin fixation) to 18.5 ± 1.41 ms at day 566 (p<0.001). Raw T2 values were therefore adjusted to correct for this fall over time. Myocardial R2 was correlated with iron concentration [Fe] (R2 0.566, p<0.001), but the correlation was stronger between LnR2 and Ln[Fe] (R2 0.790, p<0.001). The relation was [Fe] = 5081•(T2)-2.22 between T2 (ms) and myocardial iron (mg/g dry weight). Analysis of T1 proved challenging with a dichotomous distribution of T1, with very short T1 (mean 72.3 ± 25.8 ms) that was independent of iron concentration in all hearts stored in formalin for greater than 12 months. In the remaining hearts stored for <10 weeks prior to scanning, LnR1 and iron concentration were correlated but with marked scatter (R2 0.517, p<0.001). A linear relationship was present between T1 and T2 in the hearts stored for a short period (R2 0.657, p<0.001). CONCLUSION: Myocardial T2 correlates well with myocardial iron concentration, which raises the possibility that T2 may provide additive information to T2* for patients with myocardial siderosis. However, ex-vivo T1 measurements are less reliable due to the severe chemical effects of formalin on T1 shortening, and therefore T1 calibration may only be practical from in-vivo human studies.

Pelvic floor failure: MR imaging evaluation of anatomic and functional abnormalities.

Pelvic floor failure is a common disorder that can seriously jeopardize a woman's quality of life by causing urinary and fecal incontinence, difficult defecation, and pelvic pain. Multiple congenital and acquired risk factors are associated with pelvic floor failure, including altered collagen metabolism, female sex, vaginal delivery, menopause, and advanced age. A complex variety of fascial and muscular lesions that range from stretching, insertion detachment, denervation atrophy, and combinations of pelvic floor relaxation to pelvic organ prolapse may manifest in a single patient. Thorough preoperative assessment of pelvic floor failure is necessary to reduce the rate of relapse, which is reported to be as high as 30%. Magnetic resonance (MR) imaging of the pelvic floor is a two-step process that includes analysis of anatomic damage on axial fast spin-echo (FSE) T2-weighted images and functional evaluation using sagittal dynamic single-shot T2-weighted sequences during straining and defecation. This article presents high-resolution FSE T2-weighted MR images that permit detailed assessment of anatomic lesions and briefly describes pelvic floor pathophysiology, associated clinical symptoms, and patterns of dysfunction seen with dynamic MR imaging sequences. MR imaging is a powerful tool that enables radiologists to comprehensively evaluate pelvic anatomic and functional abnormalities, thus helping surgeons provide appropriate treatment and avoid repeat operations.

Chronic Total Occlusion of the Left Main and Severe Aortic Stenosis.

Concomitant aortic stenosis and coronary artery disease in the elderly population is frequent and the proper therapeutic approach is a matter of debate. We present 2 challenging cases of patients affected by severe aortic stenosis and chronic total occlusion of the left main, demonstrating the safety and feasibility of transcatheter aortic valve replacement, performed both with balloon-expandable and self-expanding valves.

Pre-TAVI imaging: an Italian survey by the CT PRotocol optimization (CT-PRO) group.

PURPOSE: The purpose of this survey was to evaluate the current state-of-art of pre-TAVI imaging in a large radiological professional community. METHODS: Between December 2022 and January 2023 all members of the Italian Society of Medical and Interventional Radiology (SIRM) were invited by the CT PRotocol Optimization group (CT-PRO group) to complete an online 24-item questionnaire about pre-TAVI imaging. RESULTS: 557 SIRM members participated in the survey. The greatest part of respondents were consultant radiologists employed in public hospitals and 84% claimed to routinely perform pre-TAVI imaging at their institutions. The most widespread acquisition protocol consisted of an ECG-gated CT angiography (CTA) scan of the aortic root and heart followed by a non-ECG-synchronized CTA of the thorax, abdomen, and pelvis. Contrast agent administration was generally tailored on the patient's body weight with a preference for using high concentration contrast media. The reports were commonly written by radiologists with expertise in cardiovascular imaging, and included all the measurements suggested by current guidelines for adequate pre-procedural planning. About 60% of the subjects affirmed that the Heart Team is present at their institutions, however only 7% of the respondents regularly attended the multidisciplinary meetings. CONCLUSIONS: This survey defines the current pre-TAVI imaging practice in a large radiological professional community. Interestingly, despite the majority of radiologists follow the current guidelines regarding acquisition and reporting of pre-TAVI imaging studies, there is still a noteworthy absence from multidisciplinary meetings and from the Heart Team.

Impact of heart magnetic resonance imaging on chelation choices, compliance with treatment and risk of heart disease in patients with thalassaemia major.

This study aimed to verify the impact of heart magnetic resonance imaging on chelation choices and patient compliance in a single-institution cohort as well as its predictive value for heart failure and arrhythmias. Abnormal cardiac T2* values determined changes in treatment in most subjects. Heart T2* was confirmed to be highly predictive over 1 year for heart failure and arrhythmias. The choice of chelation regimens known to remove heart iron efficiently was not sufficient by itself to influence the risk. Compliance with treatment had a more remarkable role.

On T2* magnetic resonance and cardiac iron.

BACKGROUND: Measurement of myocardial iron is key to the clinical management of patients at risk of siderotic cardiomyopathy. The cardiovascular magnetic resonance relaxation parameter R2* (assessed clinically via its reciprocal, T2*) measured in the ventricular septum is used to assess cardiac iron, but iron calibration and distribution data in humans are limited. METHODS AND RESULTS: Twelve human hearts were studied from transfusion-dependent patients after either death (heart failure, n=7; stroke, n=1) or transplantation for end-stage heart failure (n=4). After cardiovascular magnetic resonance R2* measurement, tissue iron concentration was measured in multiple samples of each heart with inductively coupled plasma atomic emission spectroscopy. Iron distribution throughout the heart showed no systematic variation between segments, but epicardial iron concentration was higher than in the endocardium. The mean ± SD global myocardial iron causing severe heart failure in 10 patients was 5.98 ± 2.42 mg/g dry weight (range, 3.19 to 9.50 mg/g), but in 1 outlier case of heart failure was 25.9 mg/g dry weight. Myocardial ln[R2*] was strongly linearly correlated with ln[Fe] (R²=0.910, P<0.001), leading to [Fe]=45.0×(T2*)⁻¹·²² for the clinical calibration equation with [Fe] in milligrams per gram dry weight and T2* in milliseconds. Midventricular septal iron concentration and R2* were both highly representative of mean global myocardial iron. CONCLUSIONS: These data detail the iron distribution throughout the heart in iron overload and provide calibration in humans for cardiovascular magnetic resonance R2* against myocardial iron concentration. The iron values are of considerable interest in terms of the level of cardiac iron associated with iron-related death and indicate that the heart is more sensitive to iron loading than the liver. The results also validate the current clinical practice of monitoring cardiac iron in vivo by cardiovascular magnetic resonance of the midseptum.

A pilot trial of deferiprone for neurodegeneration with brain iron accumulation.

Deferiprone was shown to reverse iron deposition in Friedreich's ataxia. This multi-center, unblinded, single-arm pilot study evaluated safety and efficacy of deferiprone for reducing cerebral iron accumulation in neurodegeneration with brain iron accumulation. Four patients with genetically-confirmed pantothenate kinase-associated neurodegeneration, and 2 with parkinsonism and focal dystonia, but inconclusive genetic tests, received 15 mg/kg deferiprone bid. Magnetic resonance imaging and neurological examinations were conducted at baseline, six and 12 months. Chelation treatment caused no apparent hematologic or neurological side effects. Magnetic resonance imaging revealed decreased iron accumulation in the globus pallidus of 2 patients (one with pantothenate kinase-associated neurodegeneration). Clinical rating scales and blinded video rating evaluations documented mild-to-moderate motor improvement in 3 patients (2 with pantothenate kinase-associated neurodegeneration). These results underline the safety and tolerability of deferiprone, and suggest that chelating treatment might be effective in improving neurological manifestations associated with iron accumulation. (Clinicaltrials.gov Identifier: NTC00907283).

A very long-term observation of a family with dilated cardiomyopathy and overlapping phenotype from lamin A/C mutation.

AIMS: We aim to describe one of the longest longitudinal follow-ups reported so far (>22 years), concerning a whole family affected by a missense lamin A/C mutation (Arg60Gly), which manifested as an overlapping phenotype with cardiac and extracardiac involvement over time. METHODS: Starting from the family history, two generations of that family were prospectively observed, from 1997 until 2020. At baseline, four individuals with dilated cardiomyopathy and cardiac conduction defects showed the same mutation. This was also found in three young individuals, phenotypically unaffected at baseline assessment. RESULTS: The prolonged clinical and laboratory evaluation has shown the evolution of an overlapping phenotype in which cardiac alterations have been associated with lipodystrophy and neurological manifestations. In the first observed generation, the prognosis was negatively affected by the progression of heart failure and lipodystrophy, whereas in the second generation the first phenotypic manifestations became evident after the 2nd decade. Cardiac magnetic resonance played a relevant role in the early detection of cardiac alteration. Right bundle branch block was another sign of initial phenotypical expression. CONCLUSION: In lamin A/C gene mutation carriers, a strict, multidisciplinary follow-up allows the opportunity to monitor the progress of the disease and to intervene precociously with the best available treatments.

International reproducibility of single breathhold T2* MR for cardiac and liver iron assessment among five thalassemia centers.

PURPOSE: To examine the reproducibility of the single breathhold T2* technique from different scanners, after installation of standard methodology in five international centers. MATERIALS AND METHODS: Up to 10 patients from each center were scanned twice locally for local interstudy reproducibility of heart and liver T2*, and then flown to a central MR facility to be rescanned on a reference scanner for intercenter reproducibility. Interobserver reproducibility for all scans was also assessed. RESULTS: Of the 49 patients scanned, the intercenter reproducibility for T2* was 5.9% for the heart and 5.8% for the liver. Local interstudy reproducibility for T2* was 7.4% for the heart and 4.6% for the liver. Interobserver reproducibility for T2* was 5.4% for the heart and 4.4% for the liver. CONCLUSION: These data indicate that T2* MR may be developed into a widespread test for tissue siderosis providing that well-defined and approved imaging and analysis techniques are used.

Right ventricular function assessed by cardiac magnetic resonance predicts the response to resynchronization therapy.

BACKGROUND AND AIM: Cardiac resynchronization therapy (CRT) reduces mortality and morbidity in chronic heart failure symptomatic patients with broad QRS who are already undergoing optimal medical treatment. However, approximately one-third of implanted patients do not show any benefit from this treatment. Right ventricle (RV) dysfunction leads to a worse outcome in patients with heart failure, but its role in predicting the response to CRT has shown conflicting results. The purpose of our study was to investigate how the RV function, assessed by cardiac magnetic resonance (CMR), could influence the outcome of heart failure patients treated with CRT. METHODS AND RESULTS: We retrospectively enrolled 72 heart failure patients, 38 affected by dilated cardiomyopathy (DCM) and 34 by ischemic dysfunction, with left bundle branch block, QRS greater than 120 ms and standard indications to CRT. We defined the response to CRT as an improvement of at least 10% of the left ventricular ejection fraction (LVEF) or at least one of the NYHA functional classes. We stratified the population into two groups based on the right ventricle ejection fraction (RVEF) at CMR: group 1 RVEF at least 55% (n = 32), group 2 RVEF less than 55% (n = 40). After a mean follow-up of 38 ±â€Š12 months, 44 patients (61%) were considered responders whereas 28 (39%) did not show any benefit. Patients in group 1 had a higher rate of response to CRT (75 vs. 50%, P = 0.03). At the univariate analysis RVEF [54 vs. 43%; confidence interval (CI) = 0.907-0.980; hazard ratio = 0.943; P = 0.003], RV end-systolic volume (56 vs. 84 ml; CI = 1.005-1.034; hazard ratio = 1.019; P = 0.008) and tricuspid annular plane systolic excursion (TAPSE) (16.4 vs. 14 mm; CI 0.745-0.976; heart rate = 0.853; P = 0.021) were the parameters most strongly associated with the response to CRT. Male sex, atrial fibrillation, and older age also negatively influenced the outcome. At a multivariate model, RVEF and older age remained significant. CONCLUSION: In our experience, patients with RV dysfunction less likely benefited from CRT. RV assessment, studied with CMR, appears to be a good predictor of the response to biventricular stimulation.

Onset of cardiac iron loading in pediatric patients with thalassemia major.

We reviewed cardiac T2* assessments from 77 thalassemia major patients between the ages of 2.5 and 18 years to study optimal timing of cardiac iron screening by magnetic resonance imaging. No patient under 9.5 years of age showed detectable cardiac iron in contrast to 36% of patients between the ages of 15-18 years old, corresponding to an odds-ratio of 1.28 (28%) per year. All patients with cardiac iron had received at least 35 grams of transfusional iron. Liver iron and ferritin failed to predict cardiac iron loading. Initiation of cardiac magnetic resonance imaging assessment should be determined according to age and transfusional burden rather than indices of iron overload. When appropriate chelation therapy has been administered since birth, cardiac magnetic resonance imaging can be postponed until 8 years of age when anesthesia is not required. Patients with suboptimal chelation, increased transfusional requirements, or who have initiated transfusions later in life should be tested sooner.

Myocardial iron overload assessment by T2* magnetic resonance imaging in adult transfusion dependent patients with acquired anemias.

Only limited data are available regarding myocardial iron overload in adult patients with transfusion dependent acquired anemias. To address this topic using MRI T2* we studied 27 consecutive chronic transfusion dependent patients with acquired anemias: (22 myelodysplastic syndrome, 5 primary myelofibrosis). Cardiac MRI T2* values obtained ranged from 5.6 to 58.7 (median value 39.8) milliseconds. Of the 24 analyzable patients, cardiac T2* correlated with transfusion burden (p=0.0002). No patient who had received less than 290 mL/kg of packed red blood cells (101 units=20 grams of iron) had a pathological cardiac T2* value (< 20 ms). All patients who had received at least 24 PRBC units showed MRI T2* detectable hepatic iron (liver T2* value

Effects of combined deferiprone and desferrioxamine iron chelating therapy in beta-thalassemia major end-stage heart failure: a case report.

Despite usual iron chelating therapy based on desferrioxamine, patients affected by beta-thalassemia major (beta-TM) often develop progressive heart failure caused by myocardial iron overload, which is the leading cause of mortality within the third decade of life. Heart transplantation is a limited therapeutic option, as very often these patients have multi-organ iron deposits and infective complications (particularly hepatitis C), secondary to frequent blood transfusions. We report the case of a 26-year-old male affected by beta-TM with end-stage heart failure, who showed a dramatic improvement in symptoms and myocardial function when a new oral iron chelating agent, deferiprone, was added to standard therapy with desferrioxamine.

Clinical Spectrum, Therapeutic Options, and Outcome of Advanced Heart Failure in Hypertrophic Cardiomyopathy.

BACKGROUND: The clinical course of patients with hypertrophic cardiomyopathy and advanced heart failure (HF) subtended by progressive left ventricular dysfunction has received limited attention. Our aim was to assess the outcome of HF and impact of treatment options including the implantable cardioverter-defibrillator and heart transplantation (HT) in patients with hypertrophic cardiomyopathy evaluated at 2 Italian referral centers >3 decades. METHODS AND RESULTS: All-cause mortality and a combined end point including death, HT, or appropriate implantable cardioverter-defibrillator shock were assessed in 71 consecutive patients with HF not related to outflow obstruction (7% of the entire hypertrophic cardiomyopathy cohort) followed up for 6.1±6.9 years after development of New York Heart Association class III to IV symptoms. At enrollment, left ventricular ejection fraction was <50% in 55 patients and >50% in 16; all had restrictive left ventricular filling. During follow-up, 35 patients died (49%%; 5-year rate, 49%) and 53 met the combined end point (75%; 5-year rate, 62%). Most events occurred in the 3 years after HF onset (17% per year compared with only 3% per year subsequently). Appropriate implantable cardioverter-defibrillator shocks occurred in 11 of 34 implanted patients. Of 37 patients evaluated for HT, 14 were transplanted, 10 listed, and 13 excluded; 2 early post-HT deaths occurred in patients with elevated pulmonary vascular resistance. Eleven of the 14 HT patients were alive at 10±8 years. CONCLUSIONS: In hypertrophic cardiomyopathy, advanced HF not associated with outflow obstruction portends a severely unfavorable prognosis, particularly in the first 3 years after onset of symptoms, despite frequently preserved systolic function in about one quarter of the patients. Outcome of HT is favorable but requires early consideration, as the window of opportunity may be short.

Efficacy and safety of deferiprone for the treatment of pantothenate kinase-associated neurodegeneration (PKAN) and neurodegeneration with brain iron accumulation (NBIA): results from a four years follow-up.

OBJECTIVE: To evaluate the long-term effect of Deferiprone (DFP) in reducing brain iron overload and improving neurological manifestations in patients with NBIA. METHODS: 6 NBIA patients (5 with genetically confirmed PKAN), received DFP solution at 15 mg/kg po bid. They were assessed by UPDRS/III and UDRS scales and blinded video rating, performed at baseline and every six months. All patients underwent brain MRI at baseline and during follow up. Quantitative assessment of brain iron was performed with T2* relaxometry, using a gradient multi-echo T2* sequence. RESULTS: After 48 months of treatment clinical rating scales and blinded video rating indicated a stabilization in motor symptoms in 5/6 Pts. In the same subjects MRI evaluation showed reduced hypointensity in the globus pallidus (GP); quantitative assessment confirmed a significant increment in the T2* value, and hence reduction of the iron content of the GP. CONCLUSION: The data from our 4-years follow-up study confirm the safety of DFP as a chelator agent for iron accumulation. The clinical stabilization observed in 5/6 of our patients suggests that DFP may be a reasonable therapeutic option for the treatment of the neurological manifestations linked with iron accumulation and neurodegeneration, especially in adult patients at early stage of the disease. (Clinicaltrials.gov identifier: NTC00907283).

Italian registry of cardiac magnetic resonance.

OBJECTIVES: Forty sites were involved in this multicenter and multivendor registry, which sought to evaluate indications, spectrum of protocols, impact on clinical decision making and safety profile of cardiac magnetic resonance (CMR). MATERIALS AND METHODS: Data were prospectively collected on a 6-month period and included 3376 patients (47.2 ± 19 years; range 1-92 years). Recruited centers were asked to complete a preliminary general report followed by a single form/patient. Referral physicians were not required to exhibit any specific certificate of competency in CMR imaging. RESULTS: Exams were performed with 1.5T scanners in 96% of cases followed by 3T (3%) and 1T (1%) magnets and contrast was administered in 84% of cases. The majority of cases were performed for the workup of inflammatory heart disease/cardiomyopathies representing overall 55.7% of exams followed by the assessment of myocardial viability and acute infarction (respectively 6.9% and 5.9% of patients). In 49% of cases the final diagnosis provided was considered relevant and with impact on patient's clinical/therapeutic management. Safety evaluation revealed 30 (0.88%) clinical events, most of which due to patient's preexisting conditions. Radiological reporting was recorded in 73% of exams. CONCLUSIONS: CMR is performed in a large number of centers in Italy with relevant impact on clinical decision making and high safety profile.