There is uncertainty regarding the clinical effects of discontinuation of drugs for heart failure after long-term use. The withdrawal of long-term treatment can follow 1 of 4 distinct patterns: 1) loss of on-treatment effect with no observed changes following discontinuation (eg, prazosin); 2) attenuation or loss of on-treatment effect with rebound clinical worsening following discontinuation (eg, nitroprusside); 3) persistence of deleterious on-treatment effect followed by clinical worsening after discontinuation (eg, milrinone and flosequinan); and 4) persistence of favorable on-treatment effect followed by clinical worsening after discontinuation (eg, digoxin and sodium-glucose cotransporter 2 inhibitors). Persuasive evidence for persistence of efficacy has been demonstrated for the use of digoxin, diuretic agents, sodium-glucose cotransporter 2 inhibitors, and (to a limited extent) for angiotensin-converting enzyme inhibitors. Available evidence for worsening of clinical status following the withdrawal of neurohormonal antagonists largely consists of observational studies. However, their findings are difficult to interpret because of considerable confounding related to the fact that drugs were withdrawn for clinical reasons, which represented a more important contributor to the poor outcome of these patients than the withdrawal of an effective drug. Nevertheless, the totality of available evidence points to a meaningful clinical deterioration within a few weeks following the withdrawal for most drugs that have been evaluated for the treatment of heart failure. These findings suggests that that our current emphasis on the implementation of foundational drugs needs to include an equally important emphasis to avoid even short-term gaps in treatment.

2023-07-01·Journal of Cardiac Failure

The First Dedicated Comprehensive Heart Failure Program in the United States: The Division of Circulatory Physiology at Columbia Presbyterian (1992–2004)

Article

作者: Packer, Milton

The first dedicated multidisciplinary heart failure program in the United States was founded as the Division of Circulatory Physiology at the Columbia University College of Physicians & Surgeons in 1992. The Division was administratively and financially independent of the Division of Cardiology and grew to 24 faculty members at its peak. Its administrative innovations included (1) a comprehensive full-integrated service line, with 2 differentiated clinical teams, one devoted to drug therapy and the other to heart transplantation and ventricular assist devices; (2) a nurse specialist/physician assistant-led clinical service; and (3) a financial structure independent of (and not supported by) other cardiovascular medical or surgical services. The division had 3 overarching missions: (1) to promote a unique career development path for each faculty member to be linked to recognition in a specific area of heart failure expertise; (2) to change the trajectory and enhance the richness of intellectual discourse in the discipline of heart failure, so as to foster an understanding of fundamental mechanisms and to develop new therapeutics; and (3) to provide optimal medical care to patients and to promote the ability of other physicians to provide optimal care. The major research achievements of the division included (1) the development of beta-blockers for heart failure, from initial hemodynamic assessments to proof-of-concept studies to large-scale international trials; (2) the development and definitive assessment of flosequinan, amlodipine, and endothelin antagonists; (3) initial clinical trials and concerns with nesiritide; (4) large-scale trials evaluating dosing of angiotensin converting-enzyme inhibitors and the efficacy and safety of neprilysin inhibition; (5) identification of key mechanisms in heart failure, including neurohormonal activation, microcirculatory endothelial dysfunction, deficiencies in peripheral vasodilator pathways, noncardiac factors in driving dyspnea, and the first identification of subphenotypes of heart failure and a preserved ejection fraction; (6) the development of a volumetric approach to the assessment of myocardial shortening; (7) conceptualization and early studies of cardiac contractility modulation as a treatment for heart failure; (8) novel approaches to the identification of cardiac allograft rejection and new therapeutics to prevent allograft vasculopathy; and (9) demonstration of the effect of left ventricular assist devices to induce reverse remodeling, and the first randomized trial showing a survival benefit with ventricular assist devices. Above all, the division served as an exceptional incubator for a generation of leaders in the field of heart failure.

2018-01-01·JACC: Heart Failure

Flosequinan

Letter

作者: Weinrauch, Larry A.

ABSTRACT The Weismann barrier postulates that genetic information passes only from the germline to the soma and not in reverse, thus providing an obstacle to the inheritance of acquired traits. Certain organisms such as planaria – flatworms that can reproduce through asymmetric fission – avoid the limitations of this barrier, thus blurring the distinction between the processes of inheritance and development. In this paper, we re-evaluate canonical ideas about the interaction between developmental, genetic and evolutionary processes through the lens of planaria. Biased distribution of epigenetic effects in asymmetrically produced parts of a regenerating organism could increase variation and therefore affect the species9 evolution. The maintenance and fixing of somatic experiences, encoded via stable biochemical or physiological states, may contribute to evolutionary processes in the absence of classically defined generations. We discuss different mechanisms that could induce asymmetry between the two organisms that eventually develop from the regenerating parts, including one particularly fascinating source – the potential capacity of the brain to produce long-lasting epigenetic changes.

100 项与氟司喹南相关的药物交易

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