Stress electrocardiography testing in coronary artery disease: Is it time for its swan song or to redefine its role in the modern era?

Stress electrocardiography (sECG) or treadmill stress testing is a well validated noninvasive diagnostic modality available to clinicians at low cost yet providing valuable functional data for coronary artery disease (CAD) diagnostic and prognostic evaluation. With the advances in cardiac imaging in both functional and anatomic fronts and the existing limitations of sECG testing, this modality appears less favored worldwide as reflected in some recent guideline updates. We review the past present and future of sECG to provide a viewpoint on where it stands in CAD evaluation and if it will remain relevant as a diagnostic modality or be retired going forward. We also provide our perspectives on how sECG can co-exist with other modalities such as calcium scoring and discuss the role of such testing in the Indian population

Positive Feedback Promotes Oscillations in Negative Feedback Loops

A simple three-component negative feedback loop is a recurring motif in biochemical oscillators. This motif oscillates as it has the three necessary ingredients for oscillations: a three-step delay, negative feedback, and nonlinearity in the loop. However, to oscillate, this motif under the common Goodwin formulation requires a high degree of cooperativity (a measure of nonlinearity) in the feedback that is biologically “unlikely.” Moreover, this recurring negative feedback motif is commonly observed augmented by positive feedback interactions. Here we show that these positive feedback interactions promote oscillation at lower degrees of cooperativity, and we can thus unify several common kinetic mechanisms that facilitate oscillations, such as self- activation and Michaelis-Menten degradation. The positive feedback loops are most beneficial when acting on the shortest lived component, where they function by balancing the lifetimes of the different components. The benefits of multiple positive feedback interactions are cumulative for a majority of situations considered, when benefits are measured by the reduction in the cooperativity required to oscillate. These positive feedback motifs also allow oscillations with longer periods than that determined by the lifetimes of the components alone. We can therefore conjecture that these positive feedback loops have evolved to facilitate oscillations at lower, kinetically achievable, degrees of cooperativity. Finally, we discuss the implications of our conclusions on the mammalian molecular clock, a system modeled extensively based on the three-component negative feedback loop

Seasonal reproduction in a fluctuating energy environment: Insolation-driven synchronized broadcast spawning in corals

*Background/Question/Methods:* Colonies of spawning corals reproduce in mass-spawning events, in which polyps within each colony release sperm and eggs for fertilization in the water column, with fertilization occurring only between gametes from different colonies. Participating colonies synchronize their gamete release to a window of a few hours once a year (for the species Acropora digitifera we study experimentally). This remarkable synchrony is essential for successful coral reproduction and thus, maintenance of the coral reef ecosystem that is currently under threat from local and global environmental effects such as pollution, global warming and ocean acidification. The mechanisms determining this tight synchrony in reproduction are not well understood, although several influences have been hypothesized and studied including lunar phase, solar insolation, and influences of temperature and tides. Moreover, most corals are in a symbiotic relationship with photosynthetic algae (Symbiodinium spp.) that live within the host tissue. Experiments supported by detailed bioenergetic modeling of the coral-algae symbiosis have shown that corals receive >90% of their energy needs from these symbionts. We develop a bioenergetic integrate-and-fire model in order to investigate whether annual insolation rhythms can entrain the gametogenetic cycles that produce mature gametes to the appropriate spawning season, since photosynthate is their primary source of energy. We solve the integrate-and-fire bioenergetic model numerically using the Fokker-Planck equation and use analytical tools such as rotation number to study entrainment.

*Results/Conclusions:* In the presence of short-term fluctuations in the energy input, our model shows that a feedback regulatory mechanism is required to achieve coherence of spawning times to within one lunar cycle, in order for subsequent cues such as lunar and diurnal light cycles to unambiguously determine the “correct” night of spawning. Entrainment to the annual insolation cycle is by itself not sufficient to produce the observed coherence in spawning. The feedback mechanism can also provide robustness against population heterogeneity due to genetic and environmental effects. We also discuss how such bioenergetic, stochastic, integrate-and-fire models are also more generally applicable: for example to aquatic insect emergence, synchrony in cell division and masting in trees

A Note on the Nutritional Requirements of the Asian Elephant (Elephas maximus indicus)

In this preliminary study, data were collected with regard to the high concentration of cobalt in palm leaf and of vitamin B12 in the blood plasma of the elephant. This suggests microbial synthesis and absorption of vitamin B12 in the elephant intestine

Coronary Risk Assessment and Management Options in Chronic Kidney Disease Patients Prior to Kidney Transplantation

Cardiovascular disease remains the most important cause of morbidity and mortality among kidney transplant recipients. Nearly half the deaths in transplanted patients are attributed to cardiac causes and almost 5% of these deaths occur within the first year after transplantation. The ideal strategies to screen for coronary artery disease (CAD) in chronic kidney disease patients who are evaluated for kidney transplantation (KT) remain controversial. The American Society of Transplantation recommends that patients with diabetes, prior history of ischemic heart disease or an abnormal ECG, or age ≥50 years should be considered as high-risk for CAD and referred for a cardiac stress test and only those with a positive stress test, for coronary angiography. Despite these recommendations, vast variations exist in the way these patients are screened for CAD at different transplant centers. The sensitivity and specificity of noninvasive cardiac tests in CKD patients is much lower than that in the general population. This has prompted the use of direct diagnostic cardiac catheterization in high-risk patients in several transplant centers despite the risks associated with this invasive procedure. No large randomized controlled trials exist to date that address these issues. In this article, we review the existing literature with regards to the available data on cardiovascular risk screening and management options in CKD patients presenting for kidney transplantation and outline a strategy for approach to these patients

Integral role of cardiovascular magnetic resonance imaging in the diagnostic workup of suspected takotsubo cardiomyopathy: Avoiding misdiagnosis

Takotsubo cardiomyopathy (TC), or stress cardiomyopathy, is an increasingly recognized acute but reversible myopathic process affecting the ventricle. Although specific criteria have been published to diagnose this entity, traditionally, coronary angiography has been used to exclude coronary artery disease in this condition. We present a case initially suspected to be TC based on clinical and angiographic data. However, cardiovascular magnetic resonance with delayed enhancement imaging with gadolinium identified occult coronary artery disease and refuted the original diagnosis of TC. Cardiovascular magnetic resonance should be an integral part of the diagnostic workup of suspected Takotsubo cardiomyopathy. (Cardiol J 2007; 14: 592-594)

Midventricular Hypertrophic Cardiomyopathy with Apical Aneurysm: Potential for Underdiagnosis and Value of Multimodality Imaging

We illustrate a case of midventricle obstructive HCM and apical aneurysm diagnosed with appropriate use of multimodality imaging. A 75-year-old African American woman presented with a 3-day history of chest pain and dyspnea with elevated troponins. Her electrocardiogram showed sinus rhythm, left atrial enlargement, left ventricular hypertrophy, prolonged QT, and occasional ectopy. After medical therapy optimization, she underwent coronary angiography for an initial diagnosis of non-ST segment elevation myocardial infarction. Her coronaries were unremarkable for significant disease but her left ventriculogram showed hyperdynamic contractility of the midportion of the ventricle along with a large dyskinetic aneurysmal apical sac. A subsequent transthoracic echocardiogram provided poor visualization of the apical region of the ventricle but contrast enhancement identified an aneurysmal pouch distal to the midventricular obstruction. To further clarify the diagnosis, cardiac magnetic resonance imaging with contrast was performed confirming the diagnosis of midventricular hypertrophic cardiomyopathy with apical aneurysm and fibrosis consistent with apical scar on delayed enhancement. The patient was medically treated and subsequently underwent elective implantable defibrillator placement in the ensuing months for recurrent nonsustained ventricular tachycardia and was initiated on prophylactic oral anticoagulation with warfarin for thromboembolic risk reduction