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

Cerebral infarction in autopsies of chagasic patients with heart failure

OBJECTIVE: To determine the frequency of encephalic infarction and its contribution to lethality in patients with Chagas' disease and heart failure. METHODS: Medical records and autopsy reports of patients with Chagas' disease complicated by heart failure, who died at the Professor Edgar Santos Hospital of the Federal University of Bahia in the past 45 years were retrospectively analyzed. Data comprised information regarding the clinical history on hospital admission, complementary and anatomicopathological examinations, including the presence of encephalic infarction, the impaired region, and the cause of death. RESULTS: Of the 5,447 autopsies performed, 524 were in patients with heart failure due to Chagas' disease. The mean age was 45.7 years, and 51 (63%) patients were of the male sex. The frequency of encephalic infarction was 17.5%, corresponding to 92 events in 92 individuals, 82 (15.8%) of which involved the brain, 8 (1.5%) involved the cerebellum, and 2 (0.4%) involved the hypophysis. CONCLUSION: Cerebral infarction has been a frequent finding in autopsies of chagasic patients with heart failure, and it has been an important cause of death in our region. The presence of cerebral infarction and its complications have been associated with death in 52% of the cases studied

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.</p

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

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 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

ON T2* MAGNETIC RESONANCE AND CARDIAC IRON

Background: Measurement of myocardial iron is key to the clinical management of patients at ris