Prevention and treatment of no-reflow phenomenon by targeting the coronary microcirculation.

The coronary no-reflow phenomenon refers to the post-percutaneous coronary intervention (PCI) state in which, despite successful revascularization of the epicardial conduit coronary arteries, substantial regions of the myocardium do not receive adequate perfusion. In most cases, the underlying mechanism can be attributed to alterations in the microvascular circulation caused by factors intrinsic or extrinsic to the coronary microcirculation. Because the no-reflow phenomenon is associated with poor clinical outcomes, it is of great importantance to identify and apply effective strategies for reducing post-PCI morbidity and mortality. Successful prevention strategies aim to ad dress increased vasoreactivity, intravascular platelet aggregation, microvascular inflammation, and down-stream plaque particle embolization. This review provides an updated overview on the pathomechanism of no-reflow and the current available prevention strategies from the perspective of coronary microcirculation. Although large randomized clinical trials have not yet identified any effective treatment, studying the coronary microcirculation may reveal new therapeutic targets for successful amelioration of the adverse clinical consequences from no-reflow phenomenon.

Emerging drugs for acute and chronic heart failure: current and future developments.

Heart failure continues to be a major public health issue. Although angiotensin-converting enzyme inhibitors and beta-adrenergic blockers have been broadly used as evidence-based therapies in heart failure, morbidity and mortality remains high. Furthermore, treatment for acute decompensated heart failure and diastolic heart failure (or 'heart failure with preserved ejection fraction') is far from perfect. This review provides a broad overview of some of the novel compounds under investigation for the treatment of heart failure. Novel strategies include drugs that aim to alleviate congestion and improve hemodynamics, drugs that preserve renal function, drugs that reduce arterial and myocardial stiffness, drugs that module myocardial contractility, drugs that affect metabolic and hormonal balance, and drugs that act on existing and novel physiologic targets.

Modelling and optimizing a system for testing electronic circuit boards.

In this article we consider a difficult combinatorial optimization problem arising from the operation of a system for testing electronic circuit boards (ECB). This problem was proposed to us by a company that makes a system for testing ECBs and is looking for an efficient way of planning the tests on any given ECB. Because of its difficulty, we first split the problem into a covering subproblem and a sequencing subproblem. We also give a global formulation of the test planning problem. Then we present and discuss results pertaining to the covering and sequencing subproblems. These results demonstrate that their solution yields testing plans that are much better than those currently used by the company. Finally we conclude our article by outlining avenues for future research.

Anomalous coronary artery found in the syncopal workup of an elderly man.

Syncope, defined as a transient loss of consciousness, is seen in 1% of all visits to emergency departments and urgent care clinics in the United States. Syncope is categorized as cardiogenic, neurologic, or psychogenic. Anomalies of the coronary arteries are rare, and anomalous coronary arteries present as syncope more often in the young than in the elderly; syncope rarely occurs in patients 65 years of age and older. There are 2 major variants of coronary anomalies. In the first variant, the left main coronary artery arises from the right aortic sinus. In the second variant, the right coronary artery arises from the left aortic sinus. The risk of sudden death is higher in patients with the left coronary artery arising from the right aortic sinus. We present a case of an anomalous coronary artery discovered during the syncopal workup in a 66-year-old man because no such cases have been published in the United States. We will discuss the management of anomalous coronary arteries as well as a systematic approach to the diagnosis and management of syncope.

Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system.

OBJECTIVES: We sought to determine whether circulating soluble angiotensin-converting enzyme 2 (sACE2) is increased in the plasma of patients with heart failure (HF). BACKGROUND: Angiotensin-converting enzyme 2 (ACE2) is an integral membrane protein that antagonizes the actions of angiotensin II and prevents the development of HF in animal models. However, because of the need for invasive cardiac tissue sampling, little is known about whether ACE2 is involved in the pathophysiology of HF in humans. METHODS: We developed a sensitive and specific assay to measure sACE2 activity in human plasma and screened a heterogeneous group of patients suspected of having clinical HF. RESULTS: Increasing sACE2 plasma activity strongly correlated with a clinical diagnosis of HF (p = 0.0002), worsening left ventricular ejection fraction (p < 0.0001), and increasing B-type natriuretic peptide levels (p < 0.0001). Similar to B-type natriuretic peptide, sACE2 activity reflected the severity of HF, with increasing levels associated with worsening New York Heart Association functional class (p < 0.0001). These associations were independent of other disease states and medication use. We found that sACE2 activity was increased in patients with both ischemic and nonischemic cardiomyopathies and also in patients with clinical HF but a preserved left ventricular ejection fraction. CONCLUSIONS: Soluble ACE2 activity is increased in patients with HF and correlates with disease severity, suggesting that a cardioprotective arm of the renin-angiotensin-aldosterone system is active in HF.

Conivaptan: potential therapeutic implications in heart failure.

Conivaptan, a dual vasopressin receptor antagonist, is a member of an emerging class of medications for the treatment of euvolemic hyponatremia. These agents induce a free-water diuresis as compared to the natriuretic effect of loop diuretics and make them an intriguing prospect for the treatment of congestive heart failure. Article also includes recent patents on this topic.