Severe left ventricular systolic dysfunction after permanent pacemaker implantation: Should we pause before upgrading to biventricular pacing?

Left ventricular (LV) systolic dysfunction leading to heart failure (HF) is known to occur after permanent pacemaker implantation (PPI) in a subset of patients. They are often treated by upgradation of the pacemaker to cardiac resynchronisation therapy (CRT). We report a case of progressive LV dysfunction and HF after PPI. Cardiac ¹⁸FDG-PET-CT scan revealed abnormal myocardial FDG uptake suggestive of cardiac sarcoidosis (CS). Biopsy from FDG avid lymph node demonstrated non-caseating granuloma. Therapy with steroids resulted in resolution of HF symptoms accompanied by a significant improvement in LV function.     

Measurements of left ventricular myocardial longitudinal systolic displacement using spectral and colour tissue Doppler: time for a reassessment?

Background

Echocardiographic measurements of left ventricular (LV) myocardial displacement may produce different results depending on the choice of employed modality and subjective adjustments during data acquisition and analysis.

Methods

In this study, left ventricular longitudinal systolic displacement was quantified in 57 patients (31 women and 26 men, 50 ± 16 years) using colour (colour TD) and spectral tissue Doppler (spectral TD) before and after temporal filtering (30 to 70 milliseconds in 20-millisecond steps) and changed offline gain saturation (0%, 50% and 100%), respectively. The results were compared with those obtained with anatomic M-mode.

Results

Whereas only minor differences occurred between the results of colour TD and anatomic M-mode measurements, spectral TD significantly overestimated the results obtained with both these methods. However, the limits of agreement between the results produced by all three studied methods were not clinically acceptable in any of the cases. The spectral TD displacement values increased along with increasing offline gain saturation whereas the effect of temporal filtering on colour Doppler measurements was insignificant.

Conclusion

Measurements of LV myocardial longitudinal displacement employing spectral TD, colour TD or anatomic M-mode produce different results, thus discouraging interchangeable use of these modalities. Whereas the results of spectral TD measurements can be significantly altered by changing offline gain setting, the effect of temporal filtering on colour TD measurements is insignificant, a fact that increases clinical practicality of the latter method.     

"Mushroom cloud": a giant left ventricular pseudoaneurysm after a myocardial infarction due to myocardial bridging – a case report

Left ventricular pseudoaneurysm is an uncommon complication after transmural myocardial infarction, occurring when a free wall rupture is contained by adhesions of the overlying pericardium preventing acute tamponade. In this report, an unusual case of a 61 year-old male with a giant apical left ventricular pseudoaneurysm after an unnoticed myocardial infarction is presented. On coronary angiogram myocardial bridging of the distal left anterior descending artery was judged to be the infarct related lesion. The echocardiographic diagnosis allowed for a timely surgical intervention which resulted in the patient's full recovery.     

Intracoronary infusion of mononuclear cells after PCI-treated myocardial infarction and arrhythmogenesis: is it safe?

To reduce long-term morbidity after revascularised acute myocardial infarction, different therapeutic strategies have been investigated. Cell therapy with mononuclear cells from bone marrow (BMMC) or peripheral blood (PBMC) has been proposed to attenuate the adverse processes of remodelling and subsequent heart failure. Previous trials have suggested that cell therapy may facilitate arrhythmogenesis. In the present substudy of the HEBE cell therapy trial, we investigated whether intracoronary cell therapy alters the prevalence of ventricular arrhythmias after 1 month or the rate of severe arrhythmogenic events (SAE) in the first year. In 164 patients of the trial we measured function and infarct size with cardiovascular magnetic resonance (CMR) imaging. Holter registration was performed after 1 month from which the number of triplets (3 successive PVCs) and ventricular tachycardias (VT, ≥4 successive PVCs) was assessed. Thirty-three patients (20%) showed triplets and/or VTs, with similar distribution amongst the groups (triplets: control n = 8 vs. BMMC n = 9, p = 1.00; vs. PBMC n = 10, p = 0.67. VT: control n = 9 vs. BMMC n = 9, p = 0.80; vs. PBMC n = 11, p = 0.69). SAE occurred in 2 patients in the PBMC group and 1 patient in the control group. In conclusion, intracoronary cell therapy is not associated with an increase in ventricular arrhythmias or SAE.     

Noninvasive assessment of left ventricular and myocardial contractility in middle-aged men and women: disparate evolution above the age of 50?

End-systolic elastance (E(es)) is a frequently used index of left ventricular (LV) contractility. However, because of its inherent dependence on LV geometry, E(es) cannot be used to compare myocardial contractile state between ventricles with different geometries, which is the case in any cross-sectional study. Various normalization methods for E(es) have been proposed in the literature, but a standardized method is still lacking. In this study, we introduced a novel alternative normalization technique and compared it with three previously suggested methods. We tested all normalization methods to assess the age- and sex-related differences in myocardial contractility in a large population sample of 2,184 middle-aged (ages, 35-55 yr) untreated subjects free from overt cardiovascular disease. Ventricular contractility E(es) was determined using a previously validated noninvasive single-beat method, based on two-dimensional echocardiographic and brachial blood pressure measurements. Myocardial contractility was estimated as 1) E(es).end-diastolic volume (EDV); 2) E(es).LV mass (LVM); 3) 0.433.E(es).LVM/relative wall thickness (RWT), based on a theoretical LV model; and 4) 0.0941.E(es).LVM(0.455).RWT(-0.159), a novel semiempirical expression derived in this study. Because of the difference in their underlying assumptions, the various myocardial contractility indexes do not provide consistent information with respect to sex differences. Despite these discrepancies, it was found that myocardial contractility in women appears to be better preserved after the age of 50 yr compared with that in men. The physiological mechanisms behind this potentially clinically important phenomenon at population level require further investigation.     

Differences in mortality from acute myocardial infarction between coronary care unit and medical ward: treatment or bias?

To analyse the effectiveness of coronary care units in reducing mortality from myocardial infarction 18 hospitals ranging from large urban teaching hospitals to small country hospitals were stratified into four levels of care. Previous analysis had failed to show significant differences in the overall mortality in hospital among levels. There were significant differences in mortality, however, between those patients allocated to be cared for in the coronary care unit and those in the medical wards in the more advanced hospitals. The differences were largest in the hospitals with the most elaborate facilities (level 1) and non-existent in those with the least (level 4). Several analytical approaches to these observed differences indicated that they were: (a) reduced by adjustment for age and severity of infarction; (b) paralleled by differences in coexisting disease recorded on death certificates; (c) no longer significant at level 1 after allowing for differences in coexisting disease; and (d) not significant at any level after exclusion of patients first diagnosed at necropsy. These findings suggest that the observed differences in mortality between coronary care units and medical wards are largely due to bias in selection and diagnosis.     

Heterochrony in Tingidae (Insecta: Heteroptera): paedomorphosis and/or peramorphosis?

Tingidae (Heteroptera: Insecta) exhibit cephalic tubercles that present a very diverse shape in larvae but that are much simpler in adults. A phylogeny based on adult and last instar characters showed that these tubercles evolved independently from simple to complex states in two clades, and reversed from complex to simple in some taxa. These homoplasies are analysed in the light of ontogenetic sequences and interpreted as heterochronic events. The general trend of evolution of the cephalic tubercles in Tingidae is in mosaic, and could be generally peramorphic, with some isolated cases of paedomorphosis.  Journal compilation © 2008 The Linnean Society of London, Biological Journal of the Linnean Society , 2008, 93 , 71–80. No claim to original French government works.     

Insights into the change in brain natriuretic peptide after ST-elevation myocardial infarction (STEMI): why should it be better than baseline?

While baseline N-terminal brain natriuretic peptide (NT-proBNP) is useful in the prognosis of acute ST-elevation myocardial infarction (STEMI), it is unclear whether a relationship exists between serial NT-proBNP, reperfusion success, and prognosis. We prospectively defined a NT-proBNP analysis in the WEST (Which Early ST-elevation myocardial infarction Therapy) trial that enrolled 304 acute STEMI patients. NT-proBNP (pg/mL) was measured at baseline prior to treatment (n=258) and 72 to 96 h (n=247) and 30 days (n=221) after treatment (Delta NT-proBNP=72 h value - the baseline NT-proBNP). Reperfusion success was measured by ST-segment resolution at 180 min, infarct size by peak creatine kinase (CK) during the first 24 h, and QRS score at discharge (QRSd). The primary endpoint was a 30 day clinical composite. The ability of either baseline NT-proBNP or Delta NT-proBNP to predict the primary endpoint was compared using single-variable logistic regression and the c-statistic. Median (interquartile range) NT-proBNP in pg/mL was 87 (39-316) at baseline, 864 (338-1857) at 72 h, and 585 (264-1212) at 30 days. ST resolution was inversely correlated with Delta NT-proBNP (r=-0.23, p=0.002) and 30 day NT-proBNP (30 day NT-proBNP 1016, 828, and 397 for <30%, 30%-70%, >or=70% STR, respectively, p<0.001). Infarct size was correlated with Delta NT-proBNP by CK (r=0.41, p<0.001) and QRSd (r=0.31, p<0.001); the 30 day NT-proBNP relationship was similar for CK (r=0.48, p<0.001) and QRSd (p=0.003). The baseline NT-proBNP was associated with an increased 30-day composite endpoint (Q1, 19%; Q2, 20%; Q3, 15%; Q4, 38%; p=0.03 for trend) as was Delta NT-proBNP (Q1, 16%; Q2, 18%; Q3, 19%; Q4, 37%; p=0.009 for trend). The c-statistic for baseline, 72 to 96 h, and Delta NT-proBNP was 0.59, 0.61, and 0.62 for the 30-day composite and 0.64, 0.62, and 0.62 for the 90-day composite, respectively. Delta NT-proBNP clearly predicts short-term adverse cardiac events and is superior to baseline NT-proBNP, but similar to the 72 to 96 h NT-proBNP in predicting clinical events after STEMI. This likely reflects the variability in NT-proBNP at presentation and the ability to integrate subsequent important physiologic sequelae of STEMI such as reperfusion and infarct size.     

Low temperature thresholds: are chill coma and CT(min) synonymous?

The effects of sub-lethal low temperatures on insect physiology and behaviour are important determinants of insect activity including foraging, mating, and predation avoidance. A substantial body of research seeks to relate the temperatures at which these activities are compromised to both, climatic conditions at species range limits and underlying physiological processes. The interpretation of this research is complicated by confusion in the names and definition of the responses measured and their associated temperature thresholds. The development of the nomenclature and explanations of the underlying physiological causes are reviewed in order to elucidate the correct sequence of responses/thresholds and associated terminologies. The results of this analysis indicate that: (1) chill coma is a clearly defined, reversible physiological state characterised by the absence of electrophysiological activity. (2) The onset of chill coma begins when low temperatures begin to impair insect behaviour and physiology, and is punctuated by a series of behavioural and/or physiological thresholds or responses. These include the temperatures at which (i) spontaneous movements cease, (ii) coordination is lost to the degree that locomotion becomes impossible, and (iii) chill coma is entered. (3) Confusion has arisen because (a) the term ‘onset of chill coma’ has been used to describe all three of these responses/thresholds and (b) the term CT_min has entered the insect literature from the vertebrate literature. These issues are discussed and a potential solution is proposed to provide clarity and consistency in the future literature.     

Moderate ischemic mitral regurgitation (IMR) and metabolic syndrome: where are we now and where are we going?

Background

The metabolic syndrome appears to affect 10% to 25% of adult population worldwide. Several studies have described the association between metabolic syndrome and ischaemic heart disease, however, none linked metabolic syndrome to ischemic mitral regurgitation, a serious clinical problem facing both the cardiologists and cardiac surgeons. Ischemic mitral regurgitation is mitral insufficiency caused by myocardial infarction. The myocardial ischemia can result in altered ventricular geometry, leading to mitral insufficiency. Interestingly metabolic syndrome showed more pronounced alteration of left ventricular geometry and function especially in obese subjects.

Presentation of the hypothesis

We have recently proposed that there is link between metabolic syndrome and ischemic mitral regurgitation and associated complications. Operative strategy for moderate ischaemic mitral regurgitation continues to be debated between revascularisation alone and concomitant valve repair at the time of coronary artery bypass surgery. Each of the above group has published studies, with results supporting each argument.

Testing the hypothesis

Generally speaking the treatments available for metabolic syndrome are based in both life style modification (dietary advice and advice to increase physical activity) and medical treatment to enhance insulin sensitivity. Randomised controlled trials may show whether the current available treatment of metabolic syndrome may have an impact on moderate ischemic mitral regurgitation.

Implications of the hypothesis

Metabolic syndrome was shown to alter left ventricular geometry and therefore it is possible to postulate that the variation in the response of different patients with moderate ischemic mitral regurgitation to current management may be attributed to the absence and presence of metabolic syndrome. Research testing of this hypothesis in the future may reveal whether concomitant treatment of metabolic syndrome will play part in the management of moderate ischemic mitral regurgitation.     

Mitochondrial dysfunction and Down's syndrome: is there a role for coenzyme Q(10) ?

Structural changes and abnormal function of mitochondria have been documented in Down's syndrome (DS) cells, patients, and animal models. DS cells in culture exhibit a wide array of functional mitochondrial abnormalities including reduced mitochondrial membrane potential, reduced ATP production, and decreased oxido-reductase activity. New research has also brought to central stage the prominent role of oxidative stress in this condition. This review focuses on recent advances in the field with a particular emphasis on novel translational approaches involving the utilization of coenzyme Q(10) (CoQ(10) ) to treat a variety of clinical phenotypes associated with DS that are linked to increased oxidative stress and energy deficits. CoQ(10) has already provided promising results in several different conditions associated with altered energy metabolism and oxidative stress in the CNS. Two studies conducted in Ancona investigated the effect of CoQ(10) treatment on DNA damage in DS patients. Although the effect of CoQ(10) was evidenced only at single cell level, the treatment affected the distribution of cells according to their content in oxidized bases. In fact, it produced a strong negative correlation linking cellular CoQ(10) content and the amount of oxidized purines. Results suggest that the effect of CoQ(10) treatment in DS not only reflects antioxidant efficacy, but likely modulates DNA repair mechanisms.     

Endocrine disruptors (EDs) and hormone-dependent cancers: Correlation or causal relationship?

The selective increase in the incidence of hormone-dependent cancers (breast, prostate, testicular) in industrialized countries is associated with the increasing number of endocrine disruptors (EDs) in the environment and raises questions about the role of EDs in mammary carcinogenesis. Answering these questions is difficult because the number of EDs is large and varies with time. Moreover hormonal carcinogenesis is multifactorial and progresses slowly and in stages. This discussion will be limited to breast cancer and three EDs: distilbene, bisphenol A (BPA), and dichlorodiphenyltrichloroethane (DDT). All these three EDs bind estrogen receptors, albeit with widely different affinities. Several complementary approaches have been used: French cancer records, epidemiological studies on cohorts followed over several decades, numerous in vitro experimental studies using cell cultures and in vivo animal studies. These approaches all converge to the same result, strongly suggesting a causal relationship between EDs and precancerous lesions. Except for distilbene, the mechanisms and molecular targets involved are still unclear, which makes it difficult to look for substitute products that are just as efficient, but less toxic.     

Festuca inops and Festuca gracilior (Poaceae): are they two different species?

According to current systematics, Festuca inops and F. gracilior are two distinct species. However, they are hardly distinguishable from each other on the basis of their morphological characters. Festuca inops is considered a diploid species endemic to Italy, while F. gracilior has a discontinuous distribution area, apparently related to chromosomal levels: diploid populations in Italy and south-east France, tetraploid populations in north-east Spain. The diploid populations of both taxa from Italy and south-east France are investigated in the present study. Nearly 1000 exsiccata were examined and morphometric analysis was carried out on macro- and micromorphological features of 119 specimens (including type-specimens) and on 20 natural populations (including loci classici ). All these data showed that the two species should be referred to a single taxon, for which the rank of species seems to be appropriate. This result is supported by karyological, ecological and chorological data and was confirmed by the results of ISSR analysis. According to nomenclatural rules, the legitimate name for the species is Festuca inops De Not.  © 2006 The Linnean Society of London, Botanical Journal of the Linnean Society , 2006, 151 , 239–258.     

Mitochondrial ('mild') uncoupling and ROS production: physiologically relevant or not?

During the last decade, the possibility that 'mild' uncoupling could be protective against oxidative damage by diminishing ROS (reactive oxygen species) production has attracted much interest. In the present paper, we briefly examine the evidence for this possibility. It is only ROS production from succinate under reverse electron-flow conditions that is sensitive to membrane potential fluctuations, and so only this type of ROS production could be affected; however, the conditions under which succinate-supported ROS production is observed include succinate concentrations that are supraphysiological. Any decrease in membrane potential, even 'mild uncoupling', must necessarily lead to large increases in respiration, i.e. it must be markedly thermogenic. Mitochondria within cells are normally ATP-producing and thus already have a diminished membrane potential, and treatment of cells, organs or animals with small amounts of artificial uncoupler does not seem to have beneficial effects that are explainable via reduced ROS production. Although it has been suggested that members of the uncoupling protein family (UCP1, UCP2 and UCP3) may mediate a mild uncoupling, present evidence does not unequivocally support such an effect, e.g. the absence of the truly uncoupling protein UCP1 is not associated with increased oxidative damage. Thus present evidence does not support mild uncoupling as a physiologically relevant alleviator of oxidative damage.     

Parmeliopsis ambigua and P. hyperopta (Parmeliaceae): species or chemotypes?

Abstract:ITS1 and ITS2 regions were sequenced from a number of Parmeliopsis ambigua andP. hyperopta specimens from Uppland, Sweden. The data were analysed cladistically and the ITS region was found to contain enough variation to support the hypothesis that the taxa should be regarded as species rather than chemotypes.     

Ceratomyxa (Myxozoa: Bivalvulida): Robust taxon or genus of convenience?

The genus Ceratomyxa (Myxozoa: Myxosporea: Bivalvulida) contains parasites that typically infect the gall bladders of marine teleosts. Species of this genus have also been recorded from elasmobranchs, while the best known species (Ceratomyxa shasta) is a systemic pathogen of fresh water salmonid fishes. Here we characterise 10 new species of Ceratomyxa from marine teleosts using morphometric and rDNA sequence data. A phylogeny of all Ceratomyxa species for which ssrDNA sequence is available was estimated by parsimony, maximum likelihood and Bayesian analyses. Mapping host fish taxonomy, geographic locality and morphology onto the phylogenetic tree provided some concordance of these characters to groups of Ceratomyxa species, but in no case was it consistent throughout the inferred phylogeny. The position of C. shasta as a sister species to the Ceratomyxa clade contradicts previous estimates of marine myxozoan phylogeny which suggested C. shasta was an unrelated lineage. Comparative DNA sequence data is available for more than 17% of some 200 described Ceratomyxa species and the genus now represents one of the most cohesive lineages within the Myxozoa. The independent branching of all atypical Ceratomyxa species and Palliatus indecorus, indicates a review of the diagnostic characters and possible division into more genera is warranted when further data are available.