Are all left bundle branch blocks the same? Myocardial mechanical implications by cardiovascular magnetic resonance.

AIMS: Left bundle branch block (LBBB) is usually associated with structural myocardial diseases progressively leading to left ventricular (LV) dysfunction. We sought to determine the mechanical implications of LBBB (as defined based on Strauss' criteria) by Cardiovascular Magnetic Resonance (CMR). METHOD AND RESULTS: We included consecutive patients referred to CMR to assess the structural cause of LBBB. CMR scans consisted of cine, stress perfusion, and late gadolinium enhancement (LGE) sequences. Myocardial deformation was assessed by tissue tracking analysis; LGE was quantified using the full width at half maximum method. We included 86 patients [63% male, 70 years (60-72)] with mean QRS duration 150 ± 13 msec. A structural disease was identified on CMR in 53% of patients (ischemic heart disease, IHD, 31%; non-ischemic heart disease, NIHD, 22%), while LBBB-related septal dyssynchrony (SD) was the only abnormality in 47%. LGE was found in 42% of patients. LVEF and myocardial deformation were impaired. Despite similar ECG characteristics, myocardial strain differed significantly between IHD, NIHD and SD patients, and patients with SD showed less impaired myocardial deformation. Indexed LV end-systolic volume and LGE extent were independently associated with impaired strain. CONCLUSIONS: Patients with LBBB show different structural and mechanical properties, and LGE extent has an unfavourable effect on myocardial mechanics.

A pilot image interpretation teaching intervention to improve competence and confidence of radiographers to detect left ventricular thrombus in routine cardiac MRI scans.

INTRODUCTION: Prompt diagnosis of left ventricular (LV) thrombus is clinically important, as it may require immediate anti-coagulation treatment. The aim of this study was to determine if a teaching intervention delivered by cardiovascular magnetic resonance (CMR) physicians would increase the CMR radiographers' ability to detect LV thrombus on a routine CMR scan. METHODS: A cohort of 25 patients (14 with and 11 without LV thrombus) were identified. A multi-parametric CMR protocol had been performed in all patients. Ten radiographers reviewed the 25 randomised anonymised studies on a workstation, documenting the presence/absence of LV thrombus and their confidence level on a 7-point Likert scale. Two senior CMR fellows then delivered a focused teaching programme to the radiographers and all 25 randomised scans were reassessed 1 month after the teaching intervention. RESULTS: Following dedicated training, there was a significant improvement in correct thrombus identification per radiographer (pre-training: 75 ± 6% vs post-training: 85 ± 6%, p = 0.009). The size of the thrombus was not associated with the likelihood of incorrectly identifying LV thrombus size prior to the training session (p = 0.2), but a trend was observed between smaller thrombus size and incorrect identifications post-training (p = 0.06). The radiographers' overall confidence in assessing the cases prior to the teaching session was high (5.6 ± 0.8 out of 7). Following the teaching session, self-reported confidence did not vary significantly (5.9 ± 0.7 out of 7, p = 0.42). When evaluating the teaching session, radiographers provided very positive feedback, rating the usefulness of the teaching intervention as highly educative (8.8 ± 0.4 out of 10). CONCLUSIONS: This is the first study that has explored the ability and confidence of CMR radiographers in detecting LV thrombus on routine CMR scans as a result of the teaching intervention delivered by CMR physicians. IMPLICATIONS FOR PRACTICE: A teaching intervention can improve CMR radiographers' diagnostic skills and diagnostic confidence.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) mimics: the knot unravelled by cardiovascular MRI.

AIM: To assess the role of cardiovascular magnetic resonance imaging (CMRI) in patients referred for suspected arrhythmogenic right ventricular cardiomyopathy (ARVC), its ability to identify ARVC mimics, and subsequent clinical impact. MATERIALS AND METHODS: The CMRI registry of the year 2014 was analysed to identify all consecutive patients referred for suspected ARVC. A comprehensive CMRI protocol that included anatomy, bi-ventricular function modules, and late gadolinium enhancement (LGE) was performed in all patients. RESULTS: Out of 2,481 CMRI performed, 124 patients (5%) were referred for suspected ARVC. A pathological substrate was identified at CMRI in 36 patients (29%): five patients (4%) had ischaemic heart disease (IHD) and 10 (8%) non-IHD; five patients (4%) met CMRI criteria for ARVC and 16 (13%) were ARVC mimics. right ventricular end-diastolic volume (RVEDV) and right ventricular stroke volume (RVSV) were significantly higher in patients with ARVC mimics (RVEDV p=0.007, RVSV p=0.012) and ARVC (RVEDV p=0.013, RVSV p=0.013), as compared to those with structurally normal hearts. CMRI was superior to echocardiography in the identification of ARVC mimics (13% versus 1%, p=0.01). CONCLUSIONS: CMRI was able to identify 16 (13%) ARVC mimics, from congenital abnormalities to acquired heart disease. CMRI was superior in identifying ARVC mimics compared to echocardiography, and overall provided a change in diagnosis in 22% of patients.

Wave intensity analysis in the internal carotid artery of hypertensive subjects using phase-contrast MR angiography and preliminary assessment of the effect of vessel morphology on wave dynamics.

OBJECTIVE: Hypertension is associated with reduced cerebral blood flow, but it is not known how this impacts on wave dynamics or potentially relates to arterial morphology. Given the location of the internal carotid artery (ICA) and risks associated with invasive measurements, wave dynamics in this artery have not been extensively assessed in vivo. This study explores the feasibility of studying wave dynamics in the internal carotid artery non-invasively. APPROACH: Normotensive, uncontrolled and controlled hypertensive participants were recruited (daytime ambulatory blood pressure <135/85 mmHg and >135/85 mmHg, respectively; n = 38). Wave intensity, reservoir pressure and statistical shape analyses were performed on the right ICA and ascending aorta high-resolution phase-contrast magnetic resonance angiography data. MAIN RESULTS: Wave speed in the aorta was significantly lower in normotensive compared to hypertensive participants (6.7 ± 1.8 versus 11.2 ± 6.2 m s-1 for uncontrolled and 11.8 ± 4.6 m s-1 for controlled hypertensives, p = 0.02), whilst there were no differences in wave speed in the ICA. There were no significant differences between the groups for the wave intensity or reservoir pressure. Interestingly, a significant association between the anatomy of the ICA and wave energy (FCW and size, r 2 = 0.12, p = 0.04) was found. SIGNIFICANCE: This study shows it is feasible to study wave dynamics in the ICA non-invasively. Whilst changes in aortic wave speed confirmed an expected increase in arterial stiffness, this was not observed in the ICA. This might suggest a protective mechanism in the cerebral circulation, in conjunction with the effect of vessel tortuosity. Furthermore, it was observed that ICA shape correlated with wave energy but not wave speed.

Out of hospital cardiac arrest survivors with inconclusive coronary angiogram: Impact of cardiovascular magnetic resonance on clinical management and decision-making.

BACKGROUND: Non-traumatic out of hospital cardiac arrest (OHCA) is the leading cause of death worldwide, mainly due to acute coronary syndromes. Urgent coronary angiography with view to revascularisation is recommended in patients with suspected acute coronary syndrome. Diagnosis and management of patients with inconclusive coronary angiogram (unobstructed coronaries or unidentified culprit lesion) is challenging. We sought to assess the role of Cardiovascular Magnetic Resonance (CMR) in the diagnosis and management of OHCA survivors with an inconclusive coronary angiogram. METHODS AND RESULTS: This is a retrospective multicentre CMR registry analysis of OHCA survivors with an inconclusive angiogram. Clinical, ECG and multi-modality imaging data were analysed. Clinical impact of CMR was defined as a change in diagnosis or management. Out of 174 OHCA survivors referred for CMR, 110 patients (63%, 84 male, median age 58) had an inconclusive angiogram. CMR identified a pathologic substrate in 76/110 patients (69%): ischemic heart disease was found in 45 (41%) and non-ischemic heart disease in 31 (28%). A structurally normal heart was found in 25 patients (23%) and non-specific findings in 9 (8%). As compared to trans-thoracic echocardiogram, CMR proved to be superior in identifying a pathologic substrate (69% vs 54%, p=0.018). The CMR study carried a clinical impact in 70% of patients, determining a change in diagnosis in 25%, in management in 29% and a change in both in 16%. CONCLUSIONS: CMR showed a promising role in the diagnostic work-up of OHCA survivors with inconclusive angiogram and its wider use should be considered.

In vitro metabolism of 1,3-dioxane, 1,3-oxathiolane, and 1,3-dithiane derivatives of theophylline: a structure-metabolism correlation study.

Correlation between structure and metabolism was studied within a series of cyclic acetal and thioacetal theophylline derivatives. All the compounds showed marked regioselectivity in in vitro metabolism, the metabolites arising only from 7-cycloalkyl side chain transformation. The 1,3-dioxane derivative, besides N-dealkylation to theophylline, underwent enzymatic ring cleavage, through the oxidation of the acetal carbon and subsequent rearrangement. Thus the acetal group was converted enzymatically to an ester. A similar transformation, catalyzed by cytochrome P450-dependent monooxygenases, was previously found for the 1,3-dioxolane ring of doxophylline. The cyclic thioacetal derivatives (i.e. 1,3-oxathiolane and 1,3-dithiane) were not cleaved during oxidative metabolism. The metabolites arise only from the oxidation of the sulfur atom, the major nucleophilic center in the molecule. No N-dealkylation to theophylline was observed. Enzymatic sulfoxidation proceeded diastereoselectively in both the 1,3-oxathiolane and 1,3-dithiane rings, the trans isomers being the major ones with a ratio trans: cis 75:25 and 60:40 respectively. The sulfoxides were stable to hydrolysis and were not further metabolized. Neither disulfoxides nor sulfones were detected in the incubations.

Metabolism of 7-(1,3-thiazolidin-2-ylmethyl)theophylline by rat liver microsomes. Evidence for a monooxygenase-dependent step in 1,3-thiazolidine ring cleavage.

Metabolic transformation of the mucoregulator and bronchodilator 7-(1,3-thiazolidin-2-ylmethyl)theophylline was studied in vitro with a rat liver microsomal preparation containing a NADPH-generating system. The only metabolite observed was 7-theophyllinacetaldehyde. In contrast to previous literature pointing out the chemical nature of 2-substituted thiazolidine ring cleavage, the formation of 7-theophyllinacetaldehyde was mediated by monooxygenase-dependent oxidation. Possibly an unstable sulfoxide was the first metabolic product, rapidly converted to 7-theophyllinacetaldehyde by hydrolysis. The sulfoxidation was apparently catalyzed mainly by flavin-containing monooxygenases, as selective thermal inactivation and methymazole significantly reduced the rate of formation of the metabolite. No N7-dealkylation pathway producing theophylline was detected, indicating a high regioselectivity in in vitro metabolism, due to the nucleophilicity of the sulfur atom.

The metabolic fate of the anti-parkinsonian drug budipine in rats.

The metabolic fate of the anti-Parkinsonian drug budipine was studied in rats after oral administration. The presence of an aromatic hydroxylation product, metabolite M1, and its O-sulphate conjugate was confirmed. Three new minor metabolites, budipine N-oxide, metabolite M1 N-oxide and a secondary metabolite derived from M1 via hydroxylation of a methyl of the tert-butyl group, were isolated and identified in rat urine. The presence of a metabolite M1-glucuronic acid conjugate, was also established through different enzymatic treatments of the rat urine.

Metabolism of 7-(1,3-dithiolan-2-ylmethyl)-1,3-dimethylxanthine by rat liver microsomes. Diastereoselective metabolism of the 1,3-dithiolane ring.

The metabolic transformation of the antibronchospastic compound ABC-99 [7-(1,3-dithiolan-2-ylmethyl)-1,3-dimethylxanthine] was studied in vitro with a rat liver microsomal preparation containing an NADPH-generating system. Thirty percent of the ABC-99 was metabolized and the only metabolic pathway observed as the oxidation of the 1,3-dithiolane ring. Two distinct sulfoxides were formed diastereoselectively, the trans isomer being the major product in the ratio 7:3. In contrast to the 1,3-dioxolane ring of doxophylline, the 1,3-dithiolane ring of ABC-99 did not undergo oxidative opening through acetal carbon oxidation. Furthermore no N-dealkylation to theophylline was observed. This high regioselectivity in in vitro metabolism was most likely due to the nucleophilicity of the sulfur atom. The diastereoselective sulfoxidation was apparently catalyzed by flavin-dependent monooxygenases, as no effect was observed with CO treatment, whereas selective thermal inactivation significantly reduced the rate of sulfoxidation.

Metabolism of 1,1-dichloro-cis-diphenylcyclopropane by rat liver microsomes.

The metabolic fate of the anti-estrogen 1,1-dichloro-cis-diphenylcyclopropane (Analog II), was studied in vitro with phenobarbital-induced rat liver microsomal fractions. The presence of five metabolites was directly or indirectly established. Biotransformation products were isolated by TLC and HPLC techniques and, when possible, the structures were confirmed through comparison with synthetic samples. The presence of an allyl chloride, highly reactive, metabolic intermediate was stated.

In vitro metabolism of 2-(5-ethylpyridin-2-yl)benzimidazole.

The in vitro metabolic transformation of the anti-inflammatory agent 2-(5-ethylpyridin-2-yl)benzimidazole (KB-1043) was studied with phenobarbital and 3-methylcholanthrene induced rat liver microsomal fractions containing an NADPH-generating system. The major metabolite was a benzylic oxidation product and a secondary metabolite was also recovered. The metabolites were isolated by TLC and HPLC techniques and identified by comparison with known pure compounds.

'In vitro' metabolism of N-picolyl-3,5-dimethylbenzamides.

'In vitro' metabolism of three isomeric N-picolyl-3,5-dimethylbenzamides was studied. The metabolites were isolated through TLC and HPLC techniques and identified by direct comparison with authentic compounds. The results of phenobarbital and 3-methyl-cholantrene inductions are given.

Metabolism of doxophylline by rat liver microsomes.

The metabolic transformation of the bronchospasmolytic agent doxophylline (2-(7'-theophyllinemethyl)-1,3-dioxolane) was studied in vitro with phenobarbital-induced rat liver microsomal fraction containing the NADPH-generating system. Doxophylline was poorly metabolized as 95% of the recovered material was parent compound. The major metabolite resulted: 2'-hydroxyethyl ester of theophylline acetic acid. This was an unusual metabolite which possibly arose from dioxolane C2 enzymatic oxydation and subsequent ring opening. Theophylline was a minor metabolite. The per cent ratio of the two metabolites was 4:1; as we did not detected the presence of any compounds formed from N-demethylation, we concluded that doxophylline underwent a regiospecific metabolism on the N7 side chain.

In vitro Metabolism of Bumetanide.

A new metabolite of the diuretic drug bumetanide, the 4-[(4'-hydroxy)-phenoxy] analog (7), was identified in incubation mixtures of rat liver microsomes. Phenobarbital and clofibrate pretreatment to induce microsomal enzymes changed the relative amounts of the six metabolites formed. Compound 7was the most prevalent metabolite after clofibrate pretreatment.

Bromination of 3-acyl-4-hydroxy-6 methyl-2H-thiopyran-2-ones. II.

The brominations of various 3-acyl-4-hydroxy-6-methyl-2H-thiopyran-2-ones as well as of 3-acyl-4-methoxy-6-methyl-2H-thiopyran-2-ones, bearing linear and branched acyl chains ranging from four to eight carbon atoms are described. The antibacterial and antimycotic activities of the new compounds are also reported.

[Changes in salivary immunoglobulin levels after cryosurgery of benign and malignant lesions of the oral cavity]. / Variazioni del tasso delle immunoglobuline salivari dopo criochirurgia di lesioni benigne e maligne del cavo orale.

The authors have evaluated variations in salivary IgA, IgG, IgM levels after cryosurgical treatment of benign and malignant oral lesions. Salivary immunoglobulin levels were measured by radial immunodiffusion before a single cryotreatment 7 and 14 days after. Seven days after cryosurgery of the lesions, there was a statistically significant increase in salivary IgG and IgM levels (p less than 0,02). These results suggest that, at the time of maximal oral cavity inflammation, 7 days after cryotreatment, there was a transudation of these immunoglobulins from serum into saliva. Salivary IgA levels decrease in a significant way (p less than 0,02) on the 14th day; this behaviour seems to be strictly connected with tumor regression after cryosurgery.