Myocardial oedema contributes to interstitial expansion and associates with mechanical and electrocardiographic changes in takotsubo syndrome: a CMR T1 and T2 mapping study.

AIMS: myocardial oedema is largely represented in takotsubo syndrome (TTS) and may contribute to alter the myocardium morphology and function. The aim of the study is to describe relationships between oedema, mechanical, and electrical abnormalities in TTS. METHODS AND RESULTS: the study included n = 32 hospitalized TTS patients and n = 23 controls. Cardiac magnetic resonance (CMR) with tissue mapping and feature tracking was performed with concomitant 12-lead electrocardiogram (ECG) recording. Mean age of TTS was 72 ± 12 years old, 94% women. Compared with controls, patients had higher left ventricular (LV) mass, worse systolic function, higher septal native T1 (1116 ± 73 msec vs. 970 ± 23 msec, P < 0.001), T2 (56 ± 5 msec vs. 46 ± 2 msec, P < 0.001), and extracellular volume (ECV) fraction (32 ± 5% vs. 24 ± 1%, P < 0.001). TTS patients had higher apicobasal gradient of T2 values (12 ± 6 msec vs. 2 ± 6 msec, P < 0.001); basal LV wall displayed higher native T1, T2, and ECV (all P < 0.002) but similar circumferential strain against controls (-23 ± 3% vs. -24 ± 4%, P = 0.351). In the TTS cohort, septal T2 values showed significant correlations with native T1 (r = 0.609, P < 0.001), ECV (r = 0.689, P < 0.001), left ventricular ejection fraction (r = -0.459, P = 0.008) and aVR voltage (r = -0.478, P = 0.009). Negative T-wave voltage and QTc length correlated with apicobasal T2 mapping gradient (r = 0.499, P = 0.007 and r = 0.372, P = 0.047, respectively) but not with other tissue mapping measurements. CONCLUSIONS: CMR T1 and T2 mapping demonstrated increased myocardial water content conditioning interstitial expansion in acute TTS, detected even outside areas of abnormal wall motion. Oedema burden and distribution associated with mechanical and electrocardiographic changes, making it a potential prognostic marker and therapeutic target in TTS.

Characterization of COVID-19-Related Lung Involvement in Patients Undergoing Magnetic Resonance T1 and T2 Mapping Imaging: A Pilot Study.

Tissue characterization by mapping techniques is a recent magnetic resonance imaging (MRI) tool that could aid the tissue characterization of lung parenchyma in coronavirus disease-2019 (COVID-19). The aim of the present study was to compare lung MRI findings, including T1 and T2 mapping, in a group of n = 11 patients with COVID-19 pneumonia who underwent a scheduled cardiac MRI, and a cohort of healthy controls. MRI scout images were used to identify affected and remote lung regions within the patients' cohort and appropriate regions of interest (ROIs) were drawn accordingly. Both lung native T1 and T2 values were significantly higher in the affected areas of patients with COVID-19 as compared to the controls (1375 ms vs. 1201 ms, p = 0.016 and 70 ms vs. 30 ms, p < 0.001, respectively), whereas no significant differences were detected between the remote lung parenchyma of the COVID-19 patients and the controls (both p > 0.05). When a larger ROI was identified, comprising the whole lung parenchyma within the image irrespective of the affected and remote areas, the COVID-19 patients still retained higher native T1 (1278 ms vs. 1149 ms, p = 0.003) and T2 values (38 ms vs. 34 ms, p = 0.04). According to the receiver operator characteristics curves, the T2 value of the affected region retained the higher accuracy for the differentiation of the COVID-19 patients against the controls (area under the curve 0.934, 95% confidence interval 0.826−0.999). These findings, possibly driven by the ability of MRI tissue mapping to detect ongoing inflammation in the lungs of patients with COVID-19, suggest that T1 and T2 mapping of the lung is a feasible approach in this clinical scenario.

Sex-specific effects of daily tadalafil on diabetic heart kinetics in RECOGITO, a randomized, double-blind, placebo-controlled trial.

Cyclic GMP-phosphodiesterase type 5 (PDE5) inhibition has been shown to counteract maladaptive cardiac changes triggered by diabetes in some but not all studies. We performed a single-center, 20-week, double-blind, randomized, placebo-controlled trial (NCT01803828) to assess sex differences in cardiac remodeling after PDE5 inhibition in patients with diabetic cardiomyopathy. A total of 122 men and women (45 to 80 years) with long-duration (>3 years) and well-controlled type 2 diabetes mellitus (T2DM; HbA1c < 86 mmol/mol) were selected according to echocardiographic signs of cardiac remodeling. Patients were randomly assigned (1:1) to placebo or oral tadalafil (20 mg, once daily). The primary outcome was to evaluate sex differences in cardiac torsion change. Secondary outcomes were changes in cardiovascular, metabolic, immune, and renal function. At 20 weeks, the treatment-by-sex interaction documented an improvement in cardiac torsion (-3.40°, -5.96; -0.84, P = 0.011) and fiber shortening (-1.19%, -2.24; -0.14, P = 0.027) in men but not women. The primary outcome could not be explained by differences in cGMP concentrations or tadalafil pharmacodynamics. In both sexes, tadalafil improved hsa-miR-199-5p expression, biomarkers of cardiovascular remodeling, albuminuria, renal artery resistive index, and circulating Klotho concentrations. Immune cell profiling revealed an improvement in low-grade chronic inflammation: Classic CD14++CD16- monocytes reduced, and Tie2+ monocytes increased. Nine patients (14.5%) had minor adverse reactions after tadalafil administration. Continuous PDE5 inhibition could offer a strategy to target cardiorenal complications of T2DM, with sex- and tissue-specific responses. Further studies are needed to confirm Klotho and hsa-miR-199-5p as markers for T2DM complications.

Heart and Lung Fibrosis in a Patient with COVID-19-Related Myocarditis.

A COVID-19 patient, in whom pneumonia lesions were first detected by chest computed tomography, was further evaluated by cardiac magnetic resonance (CMR) due to a suspected myocarditis. Beyond heart alterations, CMR revealed peculiar features of affected pulmonary areas in T1 mapping sequences and showed a particular distribution of late gadolinium enhancement in the same regions. The noninvasive assessment of the cellular, fluid, or fibrotic content of lung lesions may provide key information about the underlying pathophysiological pathways in the search of a tailored medical therapy and ventilatory support for COVID-19 patients.

Cardiac Magnetic Resonance Imaging in Immune Check-Point Inhibitor Myocarditis: A Systematic Review.

Immune checkpoint inhibitors (ICIs) are a family of anticancer drugs in which the immune response elicited against the tumor may involve other organs, including the heart. Cardiac magnetic resonance (CMR) imaging is increasingly used in the diagnostic work-up of myocardial inflammation; recently, several studies investigated the use of CMR in patients with ICI-myocarditis (ICI-M). The aim of the present systematic review is to summarize the available evidence on CMR findings in ICI-M. We searched electronic databases for relevant publications; after screening, six studies were selected, including 166 patients from five cohorts, and further 86 patients from a sub-analysis that were targeted for a tissue mapping assessment. CMR revealed mostly preserved left ventricular ejection fraction; edema prevalence ranged from 9% to 60%; late gadolinium enhancement (LGE) prevalence ranged from 23% to 83%. T1 and T2 mapping assessment were performed in 108 and 104 patients, respectively. When available, the comparison of CMR with endomyocardial biopsy revealed partial agreement between techniques and was higher for native T1 mapping amongst imaging biomarkers. The prognostic assessment was inconsistently assessed; CMR variables independently associated with the outcome included decreasing LVEF and increasing native T1. In conclusion, CMR findings in ICI-M include myocardial dysfunction, edema and fibrosis, though less evident than in more classic forms of myocarditis; native T1 mapping retained the higher concordance with EMB and significant prognostic value.

T1 and T2 Mapping in Uremic Cardiomyopathy: An Update.

Uremic cardiomyopathy (UC) is the cardiac remodelling that occurs in patients with chronic kidney disease (CKD). It is characterised by a left ventricular (LV) hypertrophy phenotype, diastolic dysfunction and generally preserved LV ejection fraction. UC has a major role mediating the increased rate of cardiovascular events, especially heart failure related, observed in patients with CKD. Recently, the use of T1 and T2 mapping techniques on cardiac MRI has expanded the ability to characterise cardiac involvement in CKD. Native T1 mapping effectively tracks the progression of interstitial fibrosis in UC, whereas T2 mapping analysis suggests the contribution of myocardial oedema, at least in a subgroup of patients. Both T1 and T2 increased values were related to worsening clinical status, myocardial injury and B-type natriuretic peptide release. Studies investigating the prognostic relevance and histology validation of mapping techniques in CKD are awaited.

Semiquantitative Chest CT Severity Score Predicts Failure of Noninvasive Positive-Pressure Ventilation in Patients Hospitalized for COVID-19 Pneumonia.

OBJECTIVE: Noninvasive positive-pressure ventilation (NPPV) emerged as an efficient tool for treatment of COVID-19 pneumonia. The factors influencing NPPV failure still are elusive. The aim of the study was to investigate the relationships between semiquantitative chest computed tomography (CT) scoring and NPPV failure and mortality in patients with COVID-19. DESIGN: Observational study. SETTING: Nonintensive care setting. PARTICIPANTS: A total of 112 patients consecutively admitted for COVID-19 pneumonia. INTERVENTIONS: Usual care including various degrees of respiratory support. MEASUREMENTS AND MAIN RESULTS: The semiquantitative CT score was calculated at hospital admission. Subgroups were identified according to the ventilation strategy used (oxygen delivered by Venturi mask n = 53; NPPV-responder n = 38; NPPV-failure n = 21). The study's primary endpoint was the use of NPPV. The secondary endpoints were NPPV failure and in-hospital death, respectively. CT score progressively increased among groups (six v nine v 14, p < 0.05 among all). CT score was an independent predictor of all study endpoints (primary endpoint: 1.25 [95% confidence interval {CI} 1.1-1.4], p = 0.001; NPPV failure: 1.41 [95% CI 1.18-1.69], p < 0.001; in-hospital mortality: 1.21 [95% CI 1.07-1.38], p = 0.003). According to receiver operator characteristics curve analysis, CT score was the most accurate variable for prediction of NPPV failure (area under the curve 0.862 with p < 0.001; p < 0.05 v other variables). CONCLUSIONS: The authors reported the common and effective use of NPPV in patients with COVID-19 pneumonia. In the authors' population, a semiquantitative chest CT analysis at hospital admission accurately identified those patients responding poorly to NPPV.

Lung Ultrasound in COVID-19: Clinical Correlates and Comparison with Chest Computed Tomography.

Lung ultrasound (LUS) and chest computed tomography (chest CT) are largely employed to evaluate coronavirus disease 2019 (COVID-19) pneumonia. We investigated semi-quantitative LUS and CT scoring in hospitalized COVID-19 patients. LUS and chest CT were performed within 24 h upon admission. Both were analyzed according to semi-quantitative scoring systems. Subgroups were identified according to median LUS score. Patients within higher LUS score group were older (79 vs 60 years, p<0.001), had higher C-reactive protein (CRP) (7.2 mg/dl vs 1.3 mg/dl, p<0.001) and chest CT score (10 vs 4, p=0.027) as well as lower PaO2/FiO2 (286 vs 356, p=0.029) as compared to patients within lower scores. We found a significant correlation between scores (r=0.390, p=0.023). Both LUS and CT scores correlated directly with patients age (r=0.586, p<0.001 and r=0.399, p=0.021 respectively) and CRP (r=0.472, p=0.002 and r=0.518, p=0.002 respectively), inversely with PaO2/FiO2 (r=-0.485, p=0.003 and r=-0.440, p=0.017 respectively). LUS score only showed significant correlation with hs-troponin T, NT-pro-BNP, and creatinine (r=0.433, p=0.019; r=0.411, p=0.027, and r=0.497, p=0.001, respectively). Semi-quantitative bedside LUS is related to the severity of COVID-19 pneumonia similarly to chest CT. Correlation of LUS score with markers of cardiac and renal injury suggests that LUS might contribute to a more comprehensive evaluation of this heterogeneous population.

Role of autonomic dysfunction in the regulation of myocardial blood flow in systemic sclerosis evaluated by cardiac magnetic resonance.

AIM: Autonomic dysfunction (AD) is an early feature of systemic sclerosis (SSc). A regular endothelial function is a prerequisite for normal response of the myocardial blood flow (MBF) to cold pressure test (CPT). The aim of the study was to evaluate the relation between MBF and AD at rest and after CPT in asymptomatic SSc patients. METHODS: Twenty SSc patients and 10 age-, sex- and body mass index-matched healthy controls underwent cardiac magnetic resonance at rest and after CPT. All subjects underwent 24 hours ambulatory 3-channel electrocardiogram Holter to evaluate AD by heart rate variability. RESULTS: We did not observe any significant difference in MBF (mL/g/min) at rest and after CPT between SSc patients and healthy controls. Delta of MBF (difference between MBF after CPT and rest MBF) was lower (P = 0.039) in SSc patients than healthy controls (0.28 [0.04-0.40] vs 0.33 [0.24-0.54]). The low frequency/high frequency (LF/HF) was higher (P = 0.002) in SSc patients than healthy controls (3 [1.7-6] vs 1.8 [1.1-2.8]). The high frequencies (HF), modulated mainly by paraympathetic system, was lower (P = 0.003) in SSc patients than healthy controls (30 [16-42] vs 36.5 [24-44]). Sympathetic hyperactivity, due to reduction of parasympathetic activity (HF), is present in SSc patients. A negative correlation was observed between Delta of MBF and LF/HF (r = -0.572, P = 0.0031). CONCLUSION: AD, characterized by sympathovagal imbalance due to a reduced parasympathetic tone with high LF/HF ratio, could be responsible for the reduced myocardial vasodilatory response after CPT.

Myocardial blood flow estimates from dynamic contrast-enhanced magnetic resonance imaging: three quantitative methods.

Dynamic contrast-enhanced cardiovascular magnetic resonance imaging can be used to quantitatively assess the myocardial blood flow (MBF), recovering the tissue impulse response function for the transit of a gadolinium bolus through the myocardium. Several deconvolution techniques are available, using various models for the impulse response. The method of choice may influence the results, producing differences that have not been deeply investigated yet. Three methods for quantifying myocardial perfusion have been compared: Fermi function modelling (FFM), the Tofts model (TM) and the gamma function model (GF), with the latter traditionally used in brain perfusion MRI. Thirty human subjects were studied at rest as well as under cold pressor test stress (submerging hands in ice-cold water), and a single bolus of gadolinium weighing 0.1 ± 0.05 mmol kg-1 was injected. Perfusion estimate differences between the methods were analysed by paired comparisons with Student's t-test, linear regression analysis, and Bland-Altman plots, as well as also using the two-way ANOVA, considering the MBF values of all patients grouped according to two categories: calculation method and rest/stress conditions. Perfusion estimates obtained by various methods in both rest and stress conditions were not significantly different, and were in good agreement with the literature. The results obtained during the first-pass transit time (20 s) yielded p-values in the range 0.20-0.28 for Student's t-test, linear regression analysis slopes between 0.98-1.03, and R values between 0.92-1.01. From the Bland-Altman plots, the paired comparisons yielded a bias (and a 95% CI)-expressed as ml/min/g-for FFM versus TM, -0.01 (-0.20, 0.17) or 0.02 (-0.49, 0.52) at rest or under stress respectively, for FFM versus GF, -0.05 (-0.29, 0.20) or -0.07 (-0.55, 0.41) at rest or under stress, and for TM versus GF, -0.03 (-0.30, 0.24) or -0.09 (-0.43, 0.26) at rest or under stress. With the two-way ANOVA, the results were p = 0.20 for the method effect (not significant), p < 0.0001 for the rest/stress condition effect (highly significant, as expected), whereas no interaction resulted between the rest/stress condition and method (p = 0.70, not significant). Considering a wider time-frame (60 s), the estimates for both rest and stress conditions were 25%-30% higher (p in the range 0.016-0.025) than those obtained in the 20 s time-frame. MBF estimates obtained by various methods under rest/stress conditions were not significantly different in the first-pass transit time, encouraging quantitative perfusion estimates in DCE-CMRI with the used methods.

First experience of real-time elastography with transvaginal approach in assessing response to MRgFUS treatment of uterine fibroids.

PURPOSE: Definition of the role of real-time elastography (RTE) in the evaluation of response to treatment of uterine fibroids using MRgFUS in symptomatic patients. MATERIALS AND METHODS: 28 women with 34 symptomatic fibroids, selected for MRgFUS, were enrolled. The patients were preliminarily studied with MRI and suprapubic and transvaginal ultrasound examination including RTE; the follow-up was performed immediately after treatment, at 3 months and 12 months with the same technique. Each lesion was evaluated by looking for ultrasound parameters (volume, resistance index) and RTE strain ratio (SR). Before and after treatment, all patients completed three questionnaires for symptom evaluation (e.g., uterine fibroids symptoms and quality of life). RESULTS: Of the 27 treated fibroids, only 14 had an effective treatment with non-perfused volume (NPV) >70 %. After 3 months of treatment, 17/21 patients presented significant decrease of uterine bleeding. A positive correlation between %NVP and percentage of fibroid volume decrease was seen. Reduction of SR value from t0 to t2 was found in 19/27 fibroids, particularly significant in fibroids with NPV > 70 %. A significant positive correlation between the percentage of symptom decrease and %SR decrease was found. At the time of statistical analysis, 12/21 patients reached the 12-month follow-up: they showed a further reduction of SR. CONCLUSION: RTE is a valid method able to support standard ultrasound examination in the evaluation of uterine fibroids, since it allows demonstrating the decrease of rigidity, which can be quantified with the SR parameter. It could be included in a pre-treatment multiparametric evaluation of patients looking for MRgFUS eligibility and in follow-up when it could assess the response to treatment.

Alternatives to surgery for the treatment of myomas.

Uterine fibroids are benign neoplasms that can cause distressing symptoms in women during their reproductive age. They are often associated with menorrhagia that can determine anemia or bulk-related symptoms. Different treatment options are available: medical therapy has the goal to treat related symptoms, while semi-invasive or non-invasive uterus-sparing procedures aim to treat symptoms and eventually to determine a reduction in fibroids size. In this review we illustrate the current semi-invasive and totally non-invasive most frequently used uterus sparing procedures available. A review of the literature along with personal experience will offer the readers a panoramic view of these up-to-date treatments to be considered as different possibilities to treat women affected by uterine fibroids looking for uterus conserving non-surgical approach.

Ultra low-dose of gadobenate dimeglumine for late gadolinium enhancement (LGE) imaging in acute myocardial infarction: a feasibility study.

PURPOSE: To assess the feasibility of using an ultra-low dose (0.05 mmol/kg of body weight [BW]) of high relaxivity contrast agent for late gadolinium enhancement (LGE) imaging in patients with acute myocardial infarction (AMI). MATERIALS AND METHODS: 17 consecutive patients (mean age, 60.1 ± 10.3 years) with ST-segment elevation AMI underwent two randomized cardiac magnetic resonance studies (exam intervals between 24 and 48h) on a 1.5T unit during the first week after the event using gadobenate dimeglumine (Gd-BOPTA) at the dose of 0.1 mmol/kg BW (standard dose or SD group) and 0.05 mmol/kg BW (half dose or HD group). Image quality was qualitatively assessed. Quantitative analysis of LGE were performed by measuring signal intensity (SI), signal-to-noise ratio (SNR) in the infarcted myocardium (IM), non-infarcted myocardium (N-IM) and left ventricular cavity (LVC) in images acquired at 1, 3, 5, 10, 15 and 20 min after administration of Gd-BOPTA using both contrast media protocol. Contrast-to-noise ratio (CNR) between IM and N-IM (CNR IM/N-IM) and between IM and LVC (CNR IM/LVC) were also quantified for each time point. Moreover the extent of infarcted myocardium was measured. RESULTS: 102 LGE images were evaluated for each dose group. Quality score was significantly higher for SD at 1, 15 and 20 min (0.002

Multi-modal CT scanning in the evaluation of cerebrovascular disease patients.

Ischemic stroke currently represents one of the leading causes of severe disability and mortality in the Western World. Until now, angiography was the most used imaging technique for the detection of the extra-cranial and intracranial vessel pathology. Currently, however, non-invasive imaging tool like ultrasound (US), magnetic resonance (MR) and computed tomography (CT) have proven capable of offering a detailed analysis of the vascular system. CT in particular represents an advanced system to explore the pathology of carotid arteries and intracranial vessels and also offers tools like CT perfusion (CTP) that provides valuable information of the brain's vascular physiology by increasing the stroke diagnostic. In this review, our purpose is to discuss stroke risk prediction and detection using CT.