A combination of right ventricular hypertrabeculation/noncompaction and arrhythmogenic right ventricular cardiomyopathy: a syndrome?

Background

Echocardiography is widely used in the management of patients with cardiogenic shock (CS). Left ventricular ejection fraction (EF) has been shown to be an independent predictor of survival in CS. Tissue Doppler Imaging (TDI) is a sensitive echocardiographic technique that allows for the early quantitative assessment of regional left ventricular dysfunction. TDI derived indices, including systolic velocity (S'), early (E') and late (A') diastolic velocities of the lateral mitral annulus, are reduced in heart failure patients (EF < 30%) and portend a poor prognosis. In CS patients, the application of TDI prior to revascularization remains unknown.

Objective

To characterize TDI derived indices in CS patients as compared to patients with chronic CHF.

Methods

Between 2006 and 2007, 100 patients were retrospectively evaluated who underwent echocardiography for assessment of LV systolic function. This population included: Group I) 50 patients (30 males, 57 ± 13 years) with chronic CHF as controls; and Group II) 50 patients (29 males, 58 ± 10 years) with CS. Spectral Doppler indices including peak early (E) and late (A) transmitral velocities, E/A ratio, and E-wave deceleration time were determined. Tissue Doppler indices including S', E' and A' velocities of the lateral annulus were measured.

Results

Of the entire cohort, the mean LVEF was 25 ± 5%. Cardiogenic shock patients demonstrated significantly lower lateral S', E' and a higher E/E' ratio (p < 0.01), as compared to CHF patients. The in-hospital mortality in the CHF cohort was 5% as compared to the CS group with an in hospital mortality of 40%. In the subset of CS patients (n = 30) who survived, the mean S' at presentation was higher as compared to those patients who died in hospital (3.5 ± 0.5 vs. 1.8 ± 0.5 cm/s).

Conclusion

Despite similar reduction in LV systolic function, CS patients have reduced myocardial velocities and higher filling pressures using TDI, as compared to CHF patients. Whether TDI could be a reliable tool to determine CS patients with the best chance of recovery following revascularization is yet to be determined.     

Genome-wide association identifies a deletion in the 3′ untranslated region of Striatin in a canine model of arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial cardiac disease characterized by ventricular arrhythmias and sudden cardiac death. It is most frequently inherited as an autosomal dominant trait with incomplete and age-related penetrance and variable clinical expression. The human disease is most commonly associated with a causative mutation in one of several genes encoding desmosomal proteins. We have previously described a spontaneous canine model of ARVC in the boxer dog. We phenotyped adult boxer dogs for ARVC by performing physical examination, echocardiogram and ambulatory electrocardiogram. Genome-wide association using the canine 50k SNP array identified several regions of association, of which the strongest resided on chromosome 17. Fine mapping and direct DNA sequencing identified an 8-bp deletion in the 3′ untranslated region (UTR) of the Striatin gene on chromosome 17 in association with ARVC in the boxer dog. Evaluation of the secondary structure of the 3′ UTR demonstrated that the deletion affects a stem loop structure of the mRNA and expression analysis identified a reduction in Striatin mRNA. Dogs that were homozygous for the deletion had a more severe form of disease based on a significantly higher number of ventricular premature complexes. Immunofluorescence studies localized Striatin to the intercalated disc region of the cardiac myocyte and co-localized it to three desmosomal proteins, Plakophilin-2, Plakoglobin and Desmoplakin, all involved in the pathogenesis of ARVC in human beings. We suggest that Striatin may serve as a novel candidate gene for human ARVC.     

Left ventricular dysfunction due to right ventricular stimulation: is biventricular upgrade really necessary?

Left ventricular (LV) dysfunction can occur due to chronic right ventricular apical pacing. Upgrading of the pacemaker to biventricular pacing is an option to reverse LV dysfunction but reprogramming of the atrioventricular (AV) timing can also be favourable. In this case report we describe the effect of AV-time reprogramming in a patient with LV function deterioration that emerged two years after implantation of a dual chamber system for sick sinus syndrome. Echocardiographc studies demonstrated a tremendous improvement in LV function during two years follow-up whereas the percentage of right ventricular pacing diminished dramatically. Careful analysis of the cause of LV deterioration can avoid unnecessary upgrading to biventricular pacing. (Neth Heart J 2010;18:604–5.)     

Cardiac-specific genetic inhibition of nuclear factor-κB prevents right ventricular hypertrophy induced by monocrotaline

Uncontrolled pulmonary arterial hypertension (PAH) results in right ventricular (RV) hypertrophy (RVH), progressive RV failure, and low cardiac output leading to increased morbidity and mortality (McLaughlin VV, Archer SL, Badesch DB, Barst RJ, Farber HW, Lindner JR, Mathier MA, McGoon MD, Park MH, Rosenson RS, Rubin LJ, Tapson VF, Varga J. J Am Coll Cardiol 53: 1573-1619, 2009). Although the exact figures of its prevalence are difficult to obtain because of the diversity of identifiable causes, it is estimated that the incidence of pulmonary hypertension is seven to nine cases per million persons in the general population and is most prevalent in the age group of 20-40, occurring more commonly in women than in men (ratio: 1.7 to 1; Rubin LJ. N Engl J Med 336: 111-117, 1997). PAH is characterized by dyspnea, chest pain, and syncope. Unfortunately, there is no cure for this disease and medical regimens are limited (Simon MA. Curr Opin Crit Care 16: 237-243, 2010). PAH leads to adverse remodeling that results in RVH, progressive right heart failure, low cardiac output, and ultimately death if left untreated (Humbert M, Morrell NW, Archer SL, Stenmark KR, MacLean MR, Lang IM, Christman BW, Weir EK, Eickelberg O, Voelkel NF, Rabinovitch M. J Am Coll Cardiol 43: 13S-24S, 2004; Humbert M, Sitbon O, Simonneau G. N Engl J Med 351: 1425-1436, 2004. LaRaia AV, Waxman AB. South Med J 100: 393-399, 2007). As there are no direct tools to assess the onset and progression of PAH and RVH, the disease is often detected in later stages marked by full-blown RVH, with the outcome predominantly determined by the level of increased afterload (D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Ann Intern Med 115: 343-349, 1991; Sandoval J, Bauerle O, Palomar A, Gomez A, Martinez-Guerra ML, Beltran M, Guerrero ML. Validation of a prognostic equation Circulation 89: 1733-1744, 1994). Various studies have been performed to assess the genetic, biochemical, and morphological components that contribute to PAH. Despite major advances in the understanding of the pathogenesis of PAH, the molecular mechanism(s) by which PAH promotes RVH and cardiac failure still remains elusive. Of all the mechanisms involved in the pathogenesis, inflammation and oxidative stress remain the core of the etiology of PAH that leads to development of RVH (Dorfmüller P, Perros F, Balabanian K, Humbert M. Eur Respir J 22: 358-363, 2003).     

Clinical characterisation and risk stratification of patients with arrhythmogenic right ventricular dysplasia/cardiomyopathy ≥50 years of age

Purpose

With the increased use of genetic testing for arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), this disease is being increasingly recognised among elderly patients. However, elderly ARVD/C patients were underrepresented in prior cohorts. We aimed to describe the phenotypical characteristics and outcomes among ARVD/C patients surviving ≥50 years.

Methods

We assessed detailed phenotypical data of 29 patients who (1) presented at ≥50 years of age; and (2) fulfilled 2010 Task Force Criteria (TFC) for ARVD/C by last follow-up. Primary outcome was the occurrence of a major ventricular arrhythmia (sudden cardiac death, resuscitated sudden cardiac arrest or sustained ventricular tachycardia).

Results

The majority (55?%) of elderly ARVD/C subjects were male, with a mean age of 59.0 ± 5.8 years at presentation. Study participants fulfilled a median of six (IQR 5–8) TFC criteria by last follow-up, of which arrhythmia criteria were most frequent (97?%), followed by structural criteria (83?%), depolarisation criteria (72?%) and repolarisation criteria (69?%). By last follow-up, 15 (52?%) patients had experienced major ventricular arrhythmias. Most patients (n = 12) presented with this arrhythmia, while three experienced the event during 5.4 ± 3.2 years of follow-up. Compared with patients without an arrhythmic event, patients with major arrhythmias were more likely to be proband (p < 0.001) and male (p = 0.042). Likewise, survival free from sustained ventricular arrhythmia was lower among probands and males.

Conclusion

Phenotypic characteristics of elderly ARVD/C patients are characterised by depolarisation abnormalities and structural cardiac changes. Ventricular arrhythmias in this elderly cohort are associated with male gender and proband status.

     

The path to Weimar Serbia? Explaining the resurgence of the Serbian far right after the fall of Milosevic

A number of European countries are experiencing a rise in the blue-collar and ethnic majority vote for the ultra-nationalist far right. The situation seems particularly ominous in Serbia, where the far right is enjoying a resurgence of electoral support, coming close to capturing the presidency in 2004. This study analyses the results of five post-Milosevic elections and finds support for the argument that the majority's economic vulnerability and a sense of ‘ethnic threat’ are the major contextual predictors of far right support. In light of the demonstrated ability of the Serbian far right to mobilize economically vulnerable sections of the population, implementation of neo-liberal economic reforms might unintentionally bring them to power. The maintenance and development of the welfare state might counteract the electoral appeal of authoritarian ultra-nationalists.     

Recruitment of marine species: Is the bandwagon rolling in the right direction?

A highly variable rate of recruitment from pelagic larval to demersal or sessile juvenile and adult stage is characteristic of marine organisms. At present it is a major subject of attention by ecologists interested in population or community processes. Several factors conspire to ensure this variability, but in studying them it will be important to focus on the behavioral capabilities of marine larvae, and on the very small proportion of (perhaps lucky) larvae destined to be successful.     

Coronary three-vessel disease with occlusion of the right coronary artery: What are the most important factors that determine the right territory perfusion?

With progressive occlusion of a coronary main artery, some anastomotic vessels are recruited in order to supply blood to the ischemic region. This collateral circulation is an important factor in the preservation of the myocardium until reperfusion of the area at risk. An accurate estimation of collateral flow is crucial in surgical bypass planning as it alters the blood flow distribution in the coronary network and can influence the outcome of a given treatment for a given patient. The evaluation of collateral flow is frequently achieved using an index based on pressure measurements. It is named collateral flow index (CFI) and defined as: (P_w − P_v)/(P_ao − P_v), where P_w is the pressure distal to the thrombosis, P_ao the aortic pressure and P_v the central venous pressure. In the present work, we study patients with severe coronary disease (stenoses on the left branches and total occlusion of the right coronary artery). Using a mathematical model that describes the coronary hemodynamics in that situation, we demonstrate that the dependence of the collateral circulation to the pressure values is not as simple as it is commonly believed: using pressures alone as an index of collateral flow is likely to result in misinterpretation of the collateral flow contribution, because collateral flow depends on many other factors related to the status of the native stenosed arteries and to the microvascular resistances (capillary and collateral resistances, and the proportion between them).     

Environmental implications of nanomaterials: are we studying the right thing?

A fundamental lack of data on the potential impacts of carbon based nanomaterials on natural ecosystems currently exists. The gap between what we know about environmental impacts and new products that may contain nanomaterials continues to get wider especially related to knowledge about nanocomposites. In this paper we present ideas and concerns about the current state of knowledge on nanomaterials in the environment and present a number of points about what recent work has provided us about the novel materials.     

Are human taste thresholds similar on the right and left sides of the tongue?

The human tongue is a relatively symmetrical anatomical structure and is generally assumed functionally equivalent on both sides. Experimental evaluation of this assumption is complicated by the fact that psychophysical measurements tend to vary considerably across testing sessions. To address functional laterality, we determined the detection thresholds of six right-handed and six left-handed subjects for Na saccharin, NaCl, citric acid and quinine HCl. Five pairs of interwoven, left and right unilateral thresholds were obtained for each taste stimulus in 12 subjects (n = 480 separate thresholds). In most cases mean sensitivity based on multiple measurements was found to be laterally symmetrical, however, we observed a few cases of lateral asymmetry of both general and compound-specific sensitivity. Threshold values were found to vary considerably across sessions, consistent with the test-retest variability previously reported for whole mouth thresholds. We conclude that taste threshold sensitivity is equivalent on the left and right anterior tongue for most individuals. Given the occasional exceptions to this rule, however, it is advisable to employ a counterbalanced design for any experimental or clinical testing protocol in which treatments are applied asymmetrically to the tongue.     

How to reach the right size?

Very little is known about how the size of an organism, or a specific tissue in an organism, is regulated. Coordinating and regulating the size of tissues is necessary for proper development, wound healing, and regeneration. Defects in a tissue-size regulation mechanism could lead to birth defects or cancer. In addition, there is a strong psychological aspect to some areas of tissue size regulation, as many cosmetic surgery procedures involve enlarging or reducing the size of some body parts. This review addresses the little bit that we know about size regulation. A key concept is that the size of a tissue is the size of the component cells multiplied by the number of those cells. This breaks the size regulation problem down to two parts. The size of cells can be regulated by nutrient sensing and secreted factors, and may have an upper limit due to an upper limit of a genome's ability to produce mRNA's and thus proteins. To regulate the number of cells in a tissue, there are several simple theoretical models involving secreted factors. In one case, the cells can secrete a characteristic factor and the concentration of the factor will increase with the number of cells secreting it, allowing the tissue to sense its own size. In another scenario, a specific cell secretes a limited amount of a factor necessary for the survival of a target population, and this then limits the size of the target population. There are currently several examples of secreted factors that regulate tissue size, including myostatin, which regulates the amount of muscles, leptin, which regulates adipose tissue, and growth hormone and insulin-like growth factors which regulate total mass. In addition, there are factors such as the found in Dictyostelium that regulate the breakup of a tissue into sub-groups. A better understanding of how these factors regulate size will hopefully allow us to develop new therapeutic procedures to treat birth defects or diseases that affect tissue size.     

Does atrial natriuretic factor protect against right ventricular overload? I. Hemodynamic study

We studied the effects of synthetic atrial natriuretic factor (ANF, 28-amino acid peptide) on base-line perfusion pressures and pressor responses to hypoxia and angiotensin II (ANG II) in isolated rat lungs and on the following hemodynamic and renal parameters in awake, chronically instrumented rats: cardiac output (CO), systemic (Rsa) and pulmonary (Rpa) vascular resistances, ANG II- and hypoxia (10.5% O2)-induced changes in Rsa and Rpa, and urine output. Intra-arterial ANF injections lowered base-line perfusion pressures and blunted hypoxia- and ANG II-induced pressor responses in the isolated lungs. Bolus intravenous injection of ANF (10 micrograms/kg) into intact rats decreased CO and arterial blood pressures of both systemic and pulmonary circulations and increased Rsa. ANG II (0.4 micrograms/kg) increased both Rsa and Rpa, and hypoxia increased Rpa alone in the intact rats. ANF (10 micrograms/kg) inhibited both ANG II- and hypoxia-induced increases in Rpa but did not significantly affect the ANG II-induced increase in Rsa. The antagonistic effect of ANF on pulmonary vasoconstriction was reversible and dose-dependent. The threshold doses of ANF required to inhibit pulmonary vasoconstriction were in the same range as those required to elicit diuresis and natriuresis. The data demonstrate that ANF has a preferential relaxant effect on pulmonary vessels constricted by hypoxia or ANG II. Both the renal and the pulmonary vascular effects of ANF may represent fundamental physiological actions of ANF. These actions may serve as a negative feedback control system that protects the right ventricle from excessive mechanical loads.     

Is analysing the nitrogen use at the plant canopy level a matter of choosing the right optimization criterion?

Herbivores can have strong deleterious effects on plant growth, reproduction, and even survival. Because these effects might be strongly interrelated, the direct consumptive effects of herbivores and a variety of indirect effects are difficult to untangle. Reductions in growth, for example, may strongly impact the flowering behaviour of plant species in the current season, but at the same time incur costs to survival, growth and reproduction in the next growing season(s). To get better insights in the effects of herbivory on the flowering behaviour of the long-lived polycarpic grassland herb Primula veris L., flowering patterns were monitored over ten consecutive years under two treatments (grazing and control mowing regimes). We tested the hypothesis that the size at flowering was affected by the presence of herbivores, and whether this translated into costs to future reproduction and survival. Overall, grazed plants were significantly smaller than control plants, and the size at which plants flowered was also significantly smaller when herbivores were present. The transition probability of flowering and of surviving into the next year was significantly smaller for all plants in the current year if they had been grazed than if they had been mown, indicating that herbivory incurred costs to both flowering and survival. Grazed plants also needed longer to start flowering, had fewer flowers and flowered less frequently, causing a significantly lower proportion of flowering adults in the population. These results suggest that the observed regression in plant size due to herbivory does not allow plants to capture enough resources to guarantee regular flowering in the longer run.     

Is ABO group incompatibility really the reason of accelerated failure of cryopreserved allografts in very young patients? – Echography assessment of the European Homograft Bank (EHB) cryopreserved allografts used for reconstruction of the right ventricular outflow tract<Superscript>*</Superscript>

Right ventricular outflow tract reconstruction (RVOTR) with cryopreserved allograft for Ross operation and other congenital or acquired cardiac malformation has become a routine and currently, the procedure of choice for children and young patients. A tendency of accelerated degeneration in the youngest recipients has been reported. Some authors advocate the ABO group incompatibility as the main reason for such failure. This retrospective monocentric study presents the long-term outcome of the European Homograft Bank (EHB) cryopreserved allografts, used for RVOTR in Ross operation (group one) and other congenital heart malformation-s (group two). The evaluation of the allograft performance was done by means of echography, considering the allografts with the transvalvular gradient of ≥40 mm Hg and/or regurgitation of ≥3+ as failed. Fifty-one patients of group one and 123 of group two were analysed after completed follow-up information. About 25.5% of patients of group one and 30.8% of group two had a compatible, whereas 74.5% of group one and 68.92 of group two an incompatible ABO group with the donor. The mean follow up was 45.77 and 68.88 months, respectively. In second group 22.76% received the aortic, while 77.24% pulmonary allograft. Only three cases of group one (5.88%) failed: one with a compatible (7.69%) and two with an incompatible ABO group (5.26%) (p = 0.1), whereas 39 patients (29.4%) of group two failed between 20.1 and 120.2 months (29.73% with and 29.07% without ABO compatibility, p = 0.03). Contrary, the age showed more importance in the allograft failure: out of 41 failed allografts, 24 (58.54%) were implanted in patients of 0–5 years (9 or 37.5% with compatible and 15 or 62.5% with incompatible ABO group). Generally, analysing both groups together, there was no influence of ABO mismatching on the allograft failure (p = 0.79). Contrary, there was a significant difference in survival between Ross and non-Ross group (p = 0.00082). This revised version was published online in July 2006 with corrections to the Cover Date.     

‘Site’ing the right reasons: critical evaluation of conservation planning for the Asiatic lion

The resurrection of Asiatic lions (Panthera leo persica) from the brink of extinction is a remarkable conservation success story. Yet, occurrence of lions as a single population makes them vulnerable to extinction from genetic and environmental factors. Asiatic lions exist as a single free ranging population of 360 individuals in Gir Protected Area (PA; about 290 lions) and surrounding satellite areas (68 lions), namely Girnar Wildlife Sanctuary (WLS), coastal areas, hill ranges extending from Mitiyala-Savarkundla-Palitana-Shihor spreading across Junagadh, Amreli and Bhavnagar districts of Gujarat State, India. This paper traces the conservation history, current conservation pressures, and critically evaluates current conservation planning based on lion ecology and existing anthropogenic pressures. Conservation proposals for translocation of lions to alternate habitats in Kuno WLS and Barda WLS are awaiting final implementation. An alternate initiative is aimed at developing satellite lion habitats, improving corridor connectivity, and facilitating natural dispersal and expansion of lion habitats. The paper evaluates human population living within 2 km boundary of lion habitats and between Gir PA and satellite habitats to show that dispersing lions have to cross heavily populated habitations taking refuge in agriculture fields and scattered forest patches. Satellite habitats vary in size from 18 km² (Mitiyala WLS) to 250 km² (scattered forests Hipavadli-Savarkundla-Palitana zone along Shetrunji river) and are inadequate to maintain natural ranging and movement requirements of territorial lions. These habitats are varied in vegetation, terrain, human pressure, and distance to source population. Though satellite lion habitats are important suboptimal habitats for dispersing lions, long-term conservation planning require planned restoration of mosaic habitats for growing populations.