LV reverse remodeling imparted by aortic valve replacement for severe aortic stenosis; is it durable? A cardiovascular MRI study sponsored by the American Heart Association

<p>Abstract</p> <p>Background</p> <p>In patients with severe aortic stenosis (AS), long-term data tracking surgically induced effects of afterload reduction on reverse LV remodeling are not available. Echocardiographic data is available short term, but in limited fashion beyond one year. Cardiovascular MRI (CMR) offers the ability to serially track changes in LV metrics with small numbers due to its inherent high spatial resolution and low variability.</p> <p>Hypothesis</p> <p>We hypothesize that changes in LV structure and function following aortic valve replacement (AVR) are detectable by CMR and once triggered by AVR, continue for an extended period.</p> <p>Methods</p> <p>Tweny-four patients of which ten (67 ± 12 years, 6 female) with severe, but compensated AS underwent CMR pre-AVR, 6 months, 1 year and up to 4 years post-AVR. 3D LV mass index, volumetrics, LV geometry, and EF were measured.</p> <p>Results</p> <p>All patients survived AVR and underwent CMR 4 serial CMR's. LVMI markedly decreased by 6 months (157 ± 42 to 134 ± 32 g/m^<b>2</b>, p < 0.005) and continued trending downwards through 4 years (127 ± 32 g/m^<b>2</b>). Similarly, EF increased pre to post-AVR (55 ± 22 to 65 ± 11%,(p < 0.05)) and continued trending upwards, remaining stable through years 1-4 (66 ± 11 vs. 65 ± 9%). LVEDVI, initially high pre-AVR, decreased post-AVR (83 ± 30 to 68 ± 11 ml/m2, p < 0.05) trending even lower by year 4 (66 ± 10 ml/m^<b>2</b>). LV stroke volume increased rapidly from pre to post-AVR (40 ± 11 to 44 ± 7 ml, p < 0.05) continuing to increase non-significantly through 4 years (49 ± 14 ml) with these LV metrics paralleling improvements in NYHA. However, LVmass/volume, a 3D measure of LV geometry, remained unchanged over 4 years.</p> <p>Conclusion</p> <p>After initial beneficial effects imparted by AVR in severe AS patients, there are, as expected, marked improvements in LV reverse remodeling. Via CMR, surgically induced benefits to LV structure and function are durable and, unexpectedly express continued, albeit markedly incomplete improvement through 4 years post-AVR concordant with sustained improved clinical status. This supports down-regulation of both mRNA and MMP activity acutely with robust suppression long term.</p

Uplifting manhood to wonderful heights? News coverage of the human costs of military conflict from world war I to Gulf war Two

Domestic political support is an important factor constraining the use of American military power around the world. Although the dynamics of war support are thought to reflect a cost-benefit calculus, with costs represented by numbers of friendly war deaths, no previous study has examined how information about friendly, enemy, and civilian casualties is routinely presented to domestic audiences. This paper establishes a baseline measure of historical casualty reporting by examining New York Times coverage of five major wars that occurred over the past century. Despite important between-war differences in the scale of casualties, the use of conscription, the type of warfare, and the use of censorship, the frequency of casualty reporting and the framing of casualty reports has remained fairly consistent over the past 100 years. Casualties are rarely mentioned in American war coverage. When casualties are reported, it is often in ways that minimize or downplay the human costs of war

A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

<p>Abstract</p> <p>Background</p> <p>Left ventricular mass (LVM) is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC). In the present study, we use association analysis to further study the genetic effect on LVM.</p> <p>Methods</p> <p>Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets.</p> <p>Results</p> <p>In the overall analysis, the most significant association was found to rs10743465, downstream of the <it>SOX5 </it>gene (p = 1.27E-05). Also, 19 additional SNPs had nominal p < 0.001. In the subset analysis, the most significant difference in genetic effect between those with high and low WC occurred with rs1157480 (p = 1.37E-04 for the difference in β coefficients), located upstream of <it>TMTC1</it>. Twelve additional SNPs in or near 6 genes had p < 0.001.</p> <p>Conclusions</p> <p>The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. <it>SOX5 </it>may play an important role in the regulation of LVM. An interaction of <it>TMTC1 </it>with abdominal obesity may contribute to phenotypic variation of LVM.</p

Cinaciguat prevents the development of pathologic hypertrophy in a rat model of left ventricular pressure overload

Pathologic myocardial hypertrophy develops when the heart is chronically pressure-overloaded. Elevated intracellular cGMP-levels have been reported to prevent the development of pathologic myocardial hypertrophy, therefore we investigated the effects of chronic activation of the cGMP producing enzyme, soluble guanylate cyclase by Cinaciguat in a rat model of pressure overload-induced cardiac hypertrophy. Abdominal aortic banding (AAB) was used to evoke pressure overload-induced cardiac hypertrophy in male Wistar rats. Sham operated animals served as controls. Experimental and control groups were treated with 10 mg/kg/day Cinaciguat (Cin) or placebo (Co) p.o. for six weeks, respectively. Pathologic myocardial hypertrophy was present in the AABCo group following 6 weeks of pressure overload of the heart, evidenced by increased relative heart weight, average cardiomyocyte diameter, collagen content and apoptosis. Cinaciguat did not significantly alter blood pressure, but effectively attenuated all features of pathologic myocardial hypertrophy, and normalized functional changes, such as the increase in contractility following AAB. Our results demonstrate that chronic enhancement of cGMP signalling by pharmacological activation of sGC might be a novel therapeutic approach in the prevention of pathologic myocardial hypertrophy

Cardiovascular magnetic resonance in pericardial diseases

The pericardium and pericardial diseases in particular have received, in contrast to other topics in the field of cardiology, relatively limited interest. Today, despite improved knowledge of pathophysiology of pericardial diseases and the availability of a wide spectrum of diagnostic tools, the diagnostic challenge remains. Not only the clinical presentation may be atypical, mimicking other cardiac, pulmonary or pleural diseases; in developed countries a shift for instance in the epidemiology of constrictive pericarditis has been noted. Accurate decision making is crucial taking into account the significant morbidity and mortality caused by complicated pericardial diseases, and the potential benefit of therapeutic interventions. Imaging herein has an important role, and cardiovascular magnetic resonance (CMR) is definitely one of the most versatile modalities to study the pericardium. It fuses excellent anatomic detail and tissue characterization with accurate evaluation of cardiac function and assessment of the haemodynamic consequences of pericardial constraint on cardiac filling. This review focuses on the current state of knowledge how CMR can be used to study the most common pericardial diseases

Integrated genomic approaches implicate osteoglycin (Ogn) in the regulation of left ventricular mass

Left ventricular mass (LVM) and cardiac gene expression are complex traits regulated by factors both intrinsic and extrinsic to the heart. To dissect the major determinants of LVM, we combined expression quantitative trait locus1 and quantitative trait transcript (QTT) analyses of the cardiac transcriptome in the rat. Using these methods and in vitro functional assays, we identified osteoglycin (Ogn) as a major candidate regulator of rat LVM, with increased Ogn protein expression associated with elevated LVM. We also applied genome-wide QTT analysis to the human heart and observed that, out of 22,000 transcripts, OGN transcript abundance had the highest correlation with LVM. We further confirmed a role for Ogn in the in vivo regulation of LVM in Ogn knockout mice. Taken together, these data implicate Ogn as a key regulator of LVM in rats, mice and humans, and suggest that Ogn modifies the hypertrophic response to extrinsic factors such as hypertension and aortic stenosi

Angiotensin-Converting Enzyme and Angiotensinogen Genes in Patterns of Left-Ventricular Hypertrophy and in Diastolic Dysfunction

1. The association of different patterns of left ventricular hypertrophy and diastolic dysfunction with angiotensin converting enzyme (ACE) genotypes or angiotensinogen dinucleotide repeat alleles were studied in human subjects. 2. Three abnormal patterns of hypertrophy (remodelled, eccentric and concentric) were associated with a history of hypertension. The presence of remodelled or concentric hypertrophy was associated with diastolic dysfunction. 3. There was no difference between the frequencies of the ACE genotypes in normotensive and hypertensive subjects, in subjects with normal ventricles and those with different patterns of left ventricular hypertrophy, nor in subjects with normal and abnormal diastolic function. Similarly, there was no difference between the relative frequencies of AGT alleles in the same clinical subgroups. 4. We conclude that in this population of hospital patients, variants of the ACE and AGT genes do not contribute to the presence of different patterns of hypertrophy or to diastolic dysfunction