Outcome in neonates with Ebstein's anomaly

AbstractThe presentation and outcome of 50 patients with neonatal Ebstein's anomaly seen from 1961 to 1990 were reviewed. The majority (88%) presented in the 1st 3 days of life; cyanosis (80%) was the most common presenting feature. Associated defects, present in 27 infants (54%), included pulmonary stenosis in 11 and atresia in 7. Nine patients (18%) died in the neonatal period; there were 15 late deaths (due to hemodynamic deterioration in 9, sudden death in 5 and a noncardiac cause in 1) at a mean age of 4.5 years (range 4 months to 19 years). Actuarial survival at 10 years was 61%.A new echocardiographic grade (1 to 4 in order of increasing severity of the defect) was devised with use of the ratio of the area of the right atrium and atrialized right ventricle to the area of the functional right ventricle and left heart chambers. Cardiac death occured in 0 of 4 infants with grade 1, 1 (10%) of 16 with grade 2, 4 (44%) of 9 with grade 3 and 5 (100%) of 5 with grade 4. In a multivariate analysis of clinical and investigational features at presentation, echocardiographic grade of severity was the best independent predictor of death.Neonates with Ebstein's anomaly have a high early mortality rate and those surviving the 1st month of life remain at high risk of late hemodynamic deterioration or sudden death. Echocardiographic grading of severity of the defect permits prognostic stratification

Apical ballooning syndrome complicated by acute severe mitral regurgitation with left ventricular outflow obstruction – Case report

BACKGROUND: Apical ballooning syndrome (or Takotsubo cardiomyopathy) is a syndrome of transient left ventricular apical ballooning. Although first described in Japanese patients, it is now well reported in the Caucasian population. The syndrome mimicks an acute myocardial infarction but is characterised by the absence of obstructive coronary disease. We describe a serious and poorly understood complication of Takotsubo cardiomyopathy. CASE PRESENTATION: We present the case of a 65 year-old lady referred to us from a rural hospital where she was treated with thrombolytic therapy for a presumed acute anterior myocardial infarction. Four hours after thrombolysis she developed acute pulmonary oedema and a new systolic murmur. It was presumed she had acute mitral regurgitation secondary to a ruptured papillary muscle, ischaemic dysfunction or an acute ventricular septal defect. Echocardiogram revealed severe mitral regurgitation, left ventricular apical ballooning, and systolic anterior motion of the mitral valve with significant left ventricular outflow tract gradient (60–70 mmHg). Coronary angiography revealed no obstructive coronary lesions. She had an intra-aortic balloon pump inserted with no improvement in her parlous haemodynamic state. We elected to replace her mitral valve to correct the outflow tract gradient and mitral regurgitation. Intra-operatively the mitral valve was mildly myxomatous but there were no structural abnormalities. She had a mechanical mitral valve replacement with a 29 mm St Jude valve. Post-operatively, her left ventricular outflow obstruction resolved and ventricular function returned to normal over the subsequent 10 days. She recovered well. CONCLUSION: This case represents a serious and poorly understood association of Takotsubo cardiomyopathy with acute pulmonary oedema, severe mitral regurgitaton and systolic anterior motion of the mitral valve with significant left ventricular outflow tract obstruction. The sequence of our patient's presentation suggests that the apical ballooning caused geometric alterations in her left ventricle that in turn led to acute and severe mitral regurgitation, systolic anterior motion of the mitral valve and left ventricular outflow tract obstruction. The left ventricular outflow tract obstruction and mitral regurgitation were corrected by mechanical mitral valve replacement. We describe a variant of Takotsubo cardiomyopathy with acute mitral regurgitation, systolic anterior motion of the mitral valve leaflet and left ventricular outflow tract obstruction of a dynamic nature

Prevalence and outcomes of low‐gradient severe aortic stenosis—from the National Echo Database of Australia

Background: The prevalence and outcomes of the different subtypes of severe low‐gradient aortic stenosis (AS) in routine clinical cardiology practice have not been well characterized. Methods and Results: Data were derived from the National Echocardiography Database of Australia. Of 192 060 adults (aged 62.8±17.8 [mean±SD] years) with native aortic valve profiling between 2000 and 2019, 12 013 (6.3%) had severe AS. Of these, 5601 patients (47%) had high‐gradient and 6412 patients (53%) had low‐gradient severe AS. The stroke volume index was documented in 2741 (42.7%) patients with low gradient; 1750 patients (64%) with low flow, low gradient (LFLG); and 991 patients with normal flow, low gradient. Of the patients with LFLG, 1570 (89.7%) had left ventricular ejection fraction recorded; 959 (61%) had paradoxical LFLG (preserved left ventricular ejection fraction), and 611 (39%) had classical LFLG (reduced left ventricular ejection fraction). All‐cause and cardiovascular‐related mortality were assessed in the 8162 patients with classifiable severe AS subtype during a mean±SD follow‐up of 88±45 months. Actual 1‐year and 5‐year all‐cause mortality rates varied across these groups and were 15.8% and 49.2% among patients with high‐gradient severe AS, 11.6% and 53.6% in patients with normal‐flow, low‐gradient severe AS, 16.9% and 58.8% in patients with paradoxical LFLG severe AS, and 30.5% and 72.9% in patients with classical LFLG severe AS. Compared with patients with high‐gradient severe AS, the 5‐year age‐adjusted and sex‐adjusted mortality risk hazard ratios were 0.94 (95% CI, 0.85–1.03) in patients with normal‐flow, low‐gradient severe AS; 1.01 (95% CI, 0.92–1.12) in patients with paradoxical LFLG severe AS; and 1.65 (95% CI, 1.48–1.84) in patients with classical LFLG severe AS. Conclusions: Approximately half of those patients with echocardiographic features of severe AS in routine clinical practice have low‐gradient hemodynamics, which is associated with long‐term mortality comparable with or worse than high‐gradient severe AS. The poorest survival was associated with classical LFLG severe AS

Altered Arterial Stiffness and Subendocardial Viability Ratio in Young Healthy Light Smokers after Acute Exercise

Studies showed that long-standing smokers have stiffer arteries at rest. However, the effect of smoking on the ability of the vascular system to respond to increased demands (physical stress) has not been studied. The purpose of this study was to estimate the effect of smoking on arterial stiffness and subendocardial viability ratio, at rest and after acute exercise in young healthy individuals.Healthy light smokers (n = 24, pack-years = 2.9) and non-smokers (n = 53) underwent pulse wave analysis and carotid-femoral pulse wave velocity measurements at rest, and 2, 5, 10, and 15 minutes following an exercise test to exhaustion. Smokers were tested, 1) after 12h abstinence from smoking (chronic condition) and 2) immediately after smoking one cigarette (acute condition). At rest, chronic smokers had higher augmentation index and lower aortic pulse pressure than non-smokers, while subendocardial viability ratio was not significantly different. Acute smoking increased resting augmentation index and decreased subendocardial viability ratio compared with non-smokers, and decreased subendocardial viability ratio compared with the chronic condition. After exercise, subendocardial viability ratio was lower, and augmentation index and aortic pulse pressure were higher in non-smokers than smokers in the chronic and acute conditions. cfPWV rate of recovery of was greater in non-smokers than chronic smokers after exercise. Non-smokers were also able to achieve higher workloads than smokers in both conditions.Chronic and acute smoking appears to diminish the vascular response to physical stress. This can be seen as an impaired 'vascular reserve' or a blunted ability of the blood vessels to accommodate the changes required to achieve higher workloads. These changes were noted before changes in arterial stiffness or subendocardial viability ratio occurred at rest. Even light smoking in young healthy individuals appears to have harmful effects on vascular function, affecting the ability of the vascular bed to respond to increased demands

Daily egg consumption in hyperlipidemic adults - Effects on endothelial function and cardiovascular risk

<p>Abstract</p> <p>Background</p> <p>Limiting consumption of eggs, which are high in cholesterol, is generally recommended to reduce risk of cardiovascular disease. However, recent evidence suggests that dietary cholesterol has limited influence on serum cholesterol or cardiac risk.</p> <p>Objective</p> <p>To assess the effects of egg consumption on endothelial function and serum lipids in hyperlipidemic adults.</p> <p>Methods</p> <p>Randomized, placebo-controlled crossover trial of 40 hyperlipidemic adults (24 women, 16 men; average age = 59.9 ± 9.6 years; weight = 76.3 ± 21.8 kilograms; total cholesterol = 244 ± 24 mg/dL). In the acute phase, participants were randomly assigned to one of the two sequences of a single dose of three medium hardboiled eggs and a sausage/cheese breakfast sandwich. In the sustained phase, participants were then randomly assigned to one of the two sequences of two medium hardboiled eggs and 1/2 cup of egg substitute daily for six weeks. Each treatment assignment was separated by a four-week washout period. Outcome measures of interest were endothelial function measured as flow mediated dilatation (FMD) and lipid panel.</p> <p>Results</p> <p>Single dose egg consumption had no effects on endothelial function as compared to sausage/cheese (0.4 ± 1.9 vs. 0.4 ± 2.4%; <it>p </it>= 0.99). Daily consumption of egg substitute for 6 weeks significantly improved endothelial function as compared to egg (1.0 ± 1.2% vs. -0.1 ± 1.5%; <it>p </it>< 0.01) and lowered serum total cholesterol (-18 ± 18 vs. -5 ± 21 mg/dL; <it>p </it>< 0.01) and LDL (-14 ± 20 vs. -2 ± 19 mg/dL; <it>p </it>= 0.01). Study results (positive or negative) are expressed in terms of change relative to baseline.</p> <p>Conclusions</p> <p>Egg consumption was found to be non-detrimental to endothelial function and serum lipids in hyperlipidemic adults, while egg substitute consumption was beneficial.</p

The relevance of tissue angiotensin-converting enzyme: manifestations in mechanistic and endpoint data

Angiotensin-converting enzyme (ACE) is primarily localized (>90%) in various tissues and organs, most notably on the endothelium but also within parenchyma and inflammatory cells. Tissue ACE is now recognized as a key factor in cardiovascular and renal diseases. Endothelial dysfunction, in response to a number of risk factors or injury such as hypertension, diabetes mellitus, hypercholesteremia, and cigarette smoking, disrupts the balance of vasodilation and vasoconstriction, vascular smooth muscle cell growth, the inflammatory and oxidative state of the vessel wall, and is associated with activation of tissue ACE. Pathologic activation of local ACE can have deleterious effects on the heart, vasculature, and the kidneys. The imbalance resulting from increased local formation of angiotensin II and increased bradykinin degradation favors cardiovascular disease. Indeed, ACE inhibitors effectively reduce high blood pressure and exert cardio- and renoprotective actions. Recent evidence suggests that a principal target of ACE inhibitor action is at the tissue sites. Pharmacokinetic properties of various ACE inhibitors indicate that there are differences in their binding characteristics for tissue ACE. Clinical studies comparing the effects of antihypertensives (especially ACE inhibitors) on endothelial function suggest differences. More comparative experimental and clinical studies should address the significance of these drug differences and their impact on clinical events

Sex differences in vascular endothelial function and health in humans: Impacts of exercise.

This brief review presents historical evidence for the purported impacts of male and female sex hormones on the vasculature in humans, including effects on macro- and micro-vascular function and health. Impacts of aging on hormonal changes and artery function are considered in the context of the menopause. Physiological data are presented alongside clinical outcomes from large trials, in an attempt to rationalise disparate findings along the bench-to-bedside continuum. Finally, the theoretical likelihood that exercise and hormone treatment may induce synergistic and/or additive vascular adaptations is developed in the context of recent laboratory studies that have compared male and female responses to training. Differences between men and women in terms of the impact of age and cardiorespiratory fitness on endothelial function are addressed. Ultimately, this review highlights the paucity of high quality and compelling evidence regarding the fundamental impact, in humans, of sex differences on arterial function and the moderating impacts of exercise on arterial function, adaptation and health at different ages in either sex. This article is protected by copyright. All rights reserved

Asymmetric Dimethylarginine, Endothelial Nitric Oxide Bioavailability and Mortality in Sepsis

Background: Plasma concentrations of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxidesynthase, are raised in patients with chronic vascular disease, causing increased cardiovascular risk and endothelialdysfunction, but the role of ADMA in acute inflammatory states is less well defined.Methods and Results: In a prospective longitudinal study in 67 patients with acute sepsis and 31 controls, digitalmicrovascular reactivity was measured by peripheral arterial tonometry and blood was collected at baseline and 2&ndash;4 dayslater. Plasma ADMA and L-arginine concentrations were determined by high performance liquid chromatography. Baselineplasma L-arginine: ADMA ratio was significantly lower in sepsis patients (median [IQR] 63 [45&ndash;103]) than in hospital controls(143 [123&ndash;166], p,0.0001) and correlated with microvascular reactivity (r = 0.34, R2 = 0.12, p = 0.02). Baseline plasma ADMAwas independently associated with 28-day mortality (Odds ratio [95% CI] for death in those in the highest quartile($0.66 mmol/L) = 20.8 [2.2&ndash;195.0], p = 0.008), and was independently correlated with severity of organ failure. Increase inADMA over time correlated with increase in organ failure and decrease in microvascular reactivity.Conclusions: Impaired endothelial and microvascular function due to decreased endothelial NO bioavailability is a potentialmechanism linking increased plasma ADMA with organ failure and death in sepsis

Justice Through a Multispecies Lens

The bushfires in Australia during the Summer of 2019–2020, in the midst of which we were writing this exchange, violently heightened the urgency of the task of rethinking justice through a multispecies lens for all of the authors in this exchange, and no doubt many of its readers. As I finish this introduction, still in the middle of the Australian summer, more than 10 million hectares (100,000 km2 or 24.7 million acres) of bushland have been burned and over a billion individual animals killed. This says nothing of the others who will die because their habitat and the relationships on which they depend no longer exist. People all around the world are mourning these deaths and the destruction of unique ecosystems. As humans on this planet, and specifically as political theorists facing the prospect that such devastating events will only become more frequent, the question before us is whether we can rethink what it means to be in ethical relationships with beings other than humans and what justice requires, in ways that mark these deaths as absolute wrongs that obligate us to act, and not simply as unfortunate tragedies that leave us bereft