Long-term cerebral thromboembolic complications of transapical endocardial resynchronization therapy.

PURPOSE: Cardiac resynchronization therapy (CRT) is an established therapeutic option in selected heart failure patients (pts). However, the transvenous left ventricular (LV) lead implantation remains ineffectual in a considerable number of pts. Transapical LV (TALV) lead implantation is an alternative minimally invasive, surgical, endocardial implantation technique. The aim of the present prospective study is to determine the long-term outcome, including the cerebral thromboembolic complications, of pts who underwent TALV lead placement. METHODS: Twenty-six CRT candidates (19 men (78 %); mean age 61 ± 10 years) with a previously failed transvenous approach underwent TALV lead placement as a last resort therapy. The following data was collected: mortality rate, reoperation rate, and cerebrovascular event rate. Patients underwent a cerebral CT scan to determine any possible cerebrovascular event related to the presence of the TALV lead. RESULTS: Eleven out of 26 (47 %) patients survived after a median follow-up of 40 ± 24.5 months. Major acute ischemic stroke occurred in two cases, while in one case transient ischemic stroke was observed. Cerebral CT scan examination performed in asymptomatic patients revealed chronic ischemic lesions with minimal extension in two patients. Reoperation occurred in one case due to TALV lead fracture. CONCLUSIONS: This is the first study reporting the long-term outcome, mortality, and thromboembolic event rate exclusively after TALV lead implantation. Patients who underwent TALV lead implantation have a comparable long-term mortality rate to conventional CRT, although a major ischemic cerebrovascular event after TALV lead implantation is worrisome and has an impact on the outcome.

Highly-functionalised difluorinated (hydroxymethyl)conduritol analogues via the Diels-Alder reactions of a difluorinated dienophile.

A difluorodienophile, synthesised using a Stille coupling reaction underwent tin(iv)-catalysed cycloaddition with three furans to afford oxa[2.2.1]bicycloheptenes in good yield. Reduction of ester and carbamate carbonyl groups and diol protection as the acetonide set the stage for palladium-catalysed hydrostannylation in two cases. Treatment of the stannanes with methyllithium triggered ring-opening to afford highly-functionalised difluorinated cyclohexenols which could be deprotected to afford (hydroxymethyl)conduritol analogues.

DOTTADs--readily made novel metal ligands with multivariant functionality.

The interaction of Hantzsch pyridinecarboxylic acids with dialkylformamides and POCl3, followed by treatment with NH4OH yields 1,8-dioxo-1,2,7,8-tetrahydro-2,7,10-triazaanthracenes (DOTTADs), which have great potential as useful ligands for Group I and II metals and some transition metals. The corresponding Hantszch esters similarly for DOTTADs or their bis-imines by way of isolable intermediates, which are then treated with an amine RNH2. DOTTAD-imines are also available from DOTTADs with amines and this reaction is also effective with 1,8-diamino-3,6-dioxaoctane to give macrocyclic analogues, as well as with chiral amines. DOTTAD-imines can be reduced with diethylsilane and Wilkinson's catalyst to the corresponding amines, which can also be formed from DOTTADs by reductive amination with amines and Na(AcO)3BH. Mono-aldols of DOTTADs are easily formed by treatment of DOTTADs with acetone.

DOTTADs--readily made novel metal ligands with multivariant functionality--trans-DOTTADs and semi-DOTTADs.

Two new ligand systems related to the previously described DOTTADs have been generated in a simple one step reaction. The first, trans-DOTTADs, were formed by Vilsmeier formylation (followed by cyclisation and N-demethylation) of 2,6-dimethyl-3,5-pyrazine-dicarboxylic acid, to give the novel bis-pyridinopyrazine dialdehyde ligands. The corresponding pyrazine diester, reacted similarly to an intermediate iminium ion stage, which gave trans-DOTTAD imines on work-up with amines. The treatment of Hantzsch ester with two equivalents of benzaldehyde gave 7-phenyl-2-(2-phenylethenyl)-7,8-dihydropyrano[4,3-b]pyridin-5-one-3-carboxylic acid. This product underwent similar cyclisation with Vilsmeier reagents to give, for example, 6-methyl-2-(2-phenylethenyl)-8-(phenylhydroxymethyl)-6H-[1,6]naphthyridin-5-one-3-carboxylic acid, an example of a semi-DOTTAD.