Brian O'Murchu

Endothelin: A New Cardiovascular Regulatory Peptide

Endothelin, a recently discovered peptide produced by endothelial cells, contracts vascular strips in vitro with greater potency than any previously known vasoconstrictor. Infusions of pharmacologic doses of endothelin in vivo result in a prolonged pressor response and a preferential impairment of renal hemodynamic and excretory functions. Endothelin also directly stimulates the release of aldosterone from the adrenal gland and inhibits renin release in vitro. A highly sensitive and specific radioimmunoassay has confirmed that endothelin circulates in human plasma, and increased plasma endothelin levels have been associated with various cardiovascular disease states. This review summarizes the current knowledge about the molecular biologic features and physiologic actions of endothelin and also explores the role of endothelin, through its local and systemic function, as a regulator of vascular tone in normal and pathophysiologic states.

Increased production of nitric oxide in coronary arteries during congestive heart failure.

Experiments were designed to determine whether a heterogeneity of endothelium-dependent relaxations in arteries from different vascular beds exists in experimental congestive heart failure (CHF) and to determine the mediators of those responses. CHF was produced in dogs by rapid ventricular pacing for 15 d. Rings of coronary, femoral, and renal arteries with and without endothelium from control and CHF dogs were suspended in organ chambers for measurement of isometric force. In arteries contracted with prostaglandin F2 alpha, endothelium-dependent relaxations to BHT 920 (an alpha 2-adrenergic agonist) were increased in coronary arteries from dogs with CHF (maximal relaxation: control -15 +/- 9% vs CHF -92 +/- 5%; n = 5-6; P < 0.05), with a modest enhancement in renal arteries. Relaxations to adenosine diphosphate and the calcium ionophore were unchanged. Relaxations to BHT 920 in CHF were reduced by NG monomethyl-L-arginine (L-NMMA) and pertussis toxin but not by indomethacin. These data suggest that endothelium-dependent relaxations are affected heterogeneously in CHF. The enhanced response to alpha 2-adrenergic agonists in the coronary artery is mediated by nitric oxide through a mechanism sensitive to inhibition by pertussis toxin. This selective increase in endothelium-dependent relaxations in the coronary artery may contribute to preserving coronary blood flow during CHF.

Study design and rationale of the heterotopic implantation of the Edwards-Sapien XT transcatheter valve in the inferior VEna cava for the treatment of severe tricuspid regurgitation (HOVER) trial.

Tricuspid regurgitation (TR) is an under treated disease. Although surgery for TR remains an effective therapy, many patients are considered to be at a high risk or otherwise inoperable. Caval valve implant (CAVI) offers an alternative to surgery in these patients. Trials assessing the safety and efficacy of caval valve implant are lacking. Methods: The Heterotopic Implantation Of the Edwards‐Sapien XT Transcatheter Valve in the Inferior VEna cava for the treatment of severe Tricuspid Regurgitation (HOVER) trial is an FDA approved, physician initiated, prospective, non‐blinded (open label), non‐randomized safety and feasibility study to determine the safety and efficacy of the heterotopic implantation of the Edwards‐Sapien XT valve in the inferior vena cava for the treatment of severe TR in patients who are at high risk or inoperable. Patients with severe TR in the absence of severe pulmonary hypertension will be recruited. They will be evaluated by a multi‐disciplinary team who will agree by consensus that the patients’ symptoms are from TR. They will undergo imaging to assess the size of the inferior vena cava (IVC) to determine feasibility of the procedure. If patients meet the inclusion criteria and are free from exclusion criteria, after informed consent they will be eligible for enrollment in the study. A total of 30 patients will be enrolled. The primary objective of the study will be to demonstrate procedural success at 30‐days and patient success at 1‐year. Conclusion: Caval valve implant may present an alternative for patients who are at high risk or inoperable for tricuspid valve surgery (TVS) for TR.

Complex atrial septal defect: percutaneous repair guided by three-dimensional echocardiography.

Three‐dimensional transesophageal echocardiography (3D TEE) has been used to guide the percutaneous repair of simple atrial septal defects (ASDs). There has been limited experience in using this imaging modality to guide complex ASD repair. In this report, we describe how 3D TEE was used to guide the repair of a complex, multifenestrated ASD. In a single view, 3D TEE provides a superior anatomic definition when compared to the traditional two‐dimensional echocardiography. We believe that this emerging technology will play a critical role as the number and complexity of percutaneous techniques treating structural heart disease continue to rise. (Echocardiography 2010;27:590‐593)

Acute anterior ST-elevation myocardial infarction and electrical storm secondary to nondominant right coronary artery occlusion.

A 42-year-old man emergently presented with chest pain and anterior ST elevation. Refractory ventricular arrhythmias and shock developed rapidly. A coronary angiogram revealed the acute occlusion of a nondominant right coronary artery. After percutaneous coronary intervention, the anterior ST elevation and ventricular arrhythmias resolved. The electrocardiographic pattern was a result of isolated right ventricular infarction that in turn caused profound electrical and hemodynamic instability. We discuss the cause and pathophysiology of this patients case, and we recommend that interventional and general cardiologists be aware that anterior ST elevation can be caused by the occlusion of a nondominant right coronary artery.

Platypnea-orthodeoxia syndrome: an unusual complication of partial liver resection.

Platypnea-orthodeoxia syndrome (POS) is a rare syndrome of severe hypoxemia upon assuming an upright position. It is classically described as shunting from the right atrium to the left atrium usually via a patent foramen ovale (PFO). Alterations in the intrathoracic anatomy after liver resection and regeneration may trigger this condition in patients with clinically silent PFO -a previously unreported cause of POS.

A YOUNG FEMALE WITH ST ELEVATION MYOCARDIAL INFARCTION AND AN OCCLUDED LEFT ANTERIOR DESCENDING ARTERY SECONDARY TO SPONTANEOUS CORONARY DISSECTION: LESS IS MORE

Spontaneous coronary artery dissection (SCAD) is a rare cause of ST-segment elevation myocardial infarction (STEMI), and is associated with lower success and increased complication rates from percutaneous revascularization. SCAD occurs most commonly in females and has an association with a recent

Exercise-induced pulmonary artery hypertension in a patient with compensated cardiac disease: hemodynamic and functional response to sildenafil therapy.

We describe the case of a 54-year-old man who presented with exertional dyspnea and fatigue that had worsened over the preceding 2 years, despite a normally functioning bioprosthetic aortic valve and stable, mild left ventricular dysfunction (left ventricular ejection fraction, 0.45). His symptoms could not be explained by physical examination, an extensive biochemical profile, or multiple cardiac and pulmonary investigations. However, abnormal cardiopulmonary exercise test results and a right heart catheterization-combined with the use of a symptom-limited, bedside bicycle ergometer-revealed that the patients exercise-induced pulmonary artery hypertension was out of proportion to his compensated left heart disease. A trial of sildenafil therapy resulted in objective improvements in hemodynamic values and functional class.

ACUTE CORONARY SYNDROME DUE TO LEFT MAIN PLAQUE RUPTURE, WITH NEGATIVE FFR AND MILD ANGIOGRAPHIC STENOSIS: TO REVASCULARIZE OR NOT?

Deferring revascularization of a hemodynamically insignificant, intermediate left main (LM) lesion in the setting of stable coronary artery disease is well established. However, in a patient with acute coronary syndrome (ACS) due a left main plaque rupture that has mild angiographic appearance and

Left main coronary artery compression syndrome and spontaneous coronary artery dissection: coincidence or pathologic association?

Left main coronary artery compression syndrome (LMCS) in patients with severe pulmonary arterial hypertension (PAH) is an unusual, and often a missed cause of exertional angina. Spontaneous coronary dissection (SCD) is a rare cause of acute coronary syndrome of unknown etiology, with predilection to women in the 20s-40s. Weather the co-presence of LMCS and SCD in certain patients is a coincidence or of pathological significance is not known. The optimal management strategy of each of these conditions remains controversial. We report a case of SCD in a patient with PAH and LMCS, successfully treated with conservative medical therapy.