Paradoxical low flow and/or low gradient severe aortic stenosis despite preserved left ventricular ejection fraction: implications for diagnosis and treatment

Paradoxical low flow, low gradient, severe aortic stenosis (AS) despite preserved ejection fraction is a recently described clinical entity whereby patients with severe AS on the basis of aortic valve area have a lower than expected gradient in relation to generally accepted values. This mode of presentation of severe AS is relatively frequent (up to 35% of cases) and such patients have a cluster of findings, indicating that they are at a more advanced stage of their disease and have a poorer prognosis if treated medically rather than surgically. Yet, a majority of these patients do not undergo surgery likely due to the fact that the reduced gradient is conducive to an underestimation of the severity of the disease and/or of symptoms. The purpose of this article is to review and further analyse the distinguishing characteristics of this entity and to present its implications with regards to currently accepted guidelines for AS severity

Induction and reversal of cardiac phenotype of human hypertrophic cardiomyopathy mutation cardiac troponin T-Q92 in switch on–switch off bigenic mice

ObjectivesThe aim of this study was to establish reversibility of cardiac phenotypes in hypertrophic cardiomyopathy (HCM) by generating bigenic mice in which expression of the mutant transgene could be turned on and off as needed.BackgroundAdvances in molecular therapeutics could ultimately lead to therapies aimed at correcting the causal mutations. However, whether cardiac phenotypes, once established, are permanent, or could be reversed, if expression of the mutant protein is turned off, is unknown.MethodsWe generated ligand-inducible bigenic mice, turned on and off expression of cardiac troponin T-Q92 (cTnT-Q92), responsible for human HCM, and characterized molecular, histologic, and functional phenotypes.ResultsWe established six lines and in dose-titration studies showed that treatment with 1,000 μg/kg of mifepristone consistently switched on cTnT-Q92 expression in the heart. Short-term (16 days) induced expression enhanced myocardial systolic function without changing myocardial cyclic adenosine monophosphate levels. Levels of PTEN, a regulator of cardiac function, phospho-protein kinase C-Ζλ-Thr538 and phosphor-protein kinase D-Ser744-748 were reduced, whereas messenger ribonucleic acid (mRNA) levels of NPPA, NPPB, and sarcoplasmic reticulum calcium adenine triphosphatase 2 (ATP2A2) (hypertrophic markers) and procollagen COL1A1, COL1A2, and COL3A1were unchanged. Long-term (70 days) induced expression increased COL1A1and COL1A3 mRNAs levels and collagen volume fraction and reduced levels of NPPAand NPPB. Switching off expression of the cTnT-Q92 reversed functional, molecular, and histologic phenotypes completely.ConclusionsThe initial phenotype induced by cTnT-Q92 is enhanced myocardial systolic function followed by changes in signaling kinases and interstitial fibrosis. Established phenotypes in HCM reverse upon turning off expression of the mutant protein. These findings provoke pursuing specific therapies directed at correcting the underlying the genetic defect in HCM

ACC/AHA Guidelines for Coronary Angiography. A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on Coronary Angiography)

"The ACC/AHA Task Force on Practice Guidelines herein revises and updates the original “Guidelines for Coronary Angiography,” published in 1987 (1). The frequent and still-growing use of coronary angiography, its relatively high costs, its inherent risks and the ongoing evolution of its indications have given this revision urgency and priority. The expert committee appointed included private practitioners and academicians. Committee members were selected to represent both experts in coronary angiography and senior clinician consultants. Representatives from the family practice and internal medicine professions were also included on the committee. The English-language medical literature was searched for the 10 years preceding development of the guidelines. The searches yielded >1,600 references that the committee reviewed for relevance. Evidence relative to the use of coronary angiography was compiled and evaluated by the committee. Whereas randomized trials are often available for reference in the development of treatment guidelines, randomized trials regarding the use of diagnostic procedures such as coronary angiography are rarely available (2). For development of these guidelines, when coronary angiography was a necessary procedure in describing a clinical subset or in choosing a course of treatment and that therapy was shown to have an advantage for the patient, especially in the context of a randomized trial, then the indication for angiography was given greater consideration than indications cited in less-rigorous evaluations of data.

ACC/AHA 2006 Guidelines for the Management of Patients With Valvular Heart Disease. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1998 Guidelines for the Management of Patients With Valvular Heart Disease)

"The ACC and the AHA have long been involved in the joint development of practice guidelines designed to assist healthcare providers in the management of selected cardiovascular disorders or the selection of certain cardiovascular procedures. The determination of the disorders or procedures to develop guidelines for is based on several factors, including importance to healthcare providers and whether there are sufficient data from which to derive accepted guidelines. One important category of cardiac disorders that affect a large number of patients who require diagnostic procedures and decisions regarding long-term management is valvular heart disease. During the past 2 decades, major advances have occurred in diagnostic techniques, the understanding of natural history, and interventional cardiology and surgical procedures for patients with valvular heart disease. These advances have resulted in enhanced diagnosis, more scientific selection of patients for surgery or catheter-based intervention versus medical management, and increased survival of patients with these disorders. The information base from which to make clinical management decisions has greatly expanded in recent years, yet in many situations, management issues remain controversial or uncertain. Unlike many other forms of cardiovascular disease, there is a scarcity of large-scale multicenter trials addressing the diagnosis and treatment of patients with valvular disease from which to derive definitive conclusions, and the information available in the literature represents primarily the experiences reported by single institutions in relatively small numbers of patients.

ACC/AHA/ASNC Guidelines for the Clinical Use of Cardiac Radionuclide Imaging—Executive Summary: A Report of the American College of Cardiology/American HeartAssociation Task Force on Practice Guidelines (ACC/AHA/ASNC Committee to Revise the 1995 Guidelines for the Clinical Use of Cardiac Radionuclide Imaging)

The American College of Cardiology (ACC)/American Heart Association (AHA) Task Force on Practice Guidelines regularly reviews existing guidelines to determine when an update or full revision is needed. Guidelines for the Clinical Use of Cardiac Radionuclide Imaging were originally published in 1986 and updated in 1995. Important new developments have continued to occur since 1995, particularly in the areas of acute and chronic ischemic syndromes and heart failure. The Task Force therefore believed the topic should be revisited de novo and invited the American Society for Nuclear Cardiology (ASNC) to cosponsor the undertaking, which represents a joint effort of the 3 organizations