Baylor Heart and Vascular Institute

Packer, M. (2017). “Will long-acting glucagon-like peptide-1 analogues recapitulate our agonizing experience with cyclic amp-dependent positive inotropic agents in heart failure?” Eur J Heart Fail: 2017 Oct [Epub ahead of print].

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Over the past three decades, substantial changes have taken place regarding our understanding of the role of cyclic AMP. It is now understood that cyclic AMP may be compartmented and that changes in subcellular pools may not have implications for cardiac contractility or cardiotoxicity.3 Treatments that increase cyclic AMP in the heart have been reported to have favourable effects on myocardial viability and angiogenesis as well as on cardiac remodelling.4,5 Phosphodiesterase inhibitors (i.e. cilostazol) have been developed for the treatment of patients with claudication, even though peripheral vascular disease and heart failure frequently coexist.

Packer, M. (2017). “Why is the use of digitalis withering? Another reason that we need medical heart failure specialists.” Eur J Heart Fail: 2017 Oct [Epub ahead of print].

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Contrary to popular opinion, William Withering did not discover digitalis nor was he the first to describe its use for heart failure. In 1785, the esteemed English botanist and physician wrote a pamphlet that summarized his experiences in 163 patients with dropsy. Yet, at the time, digitalis had been known to exert important pharmacological effects for 2000 years. In the first century, the Greek physician, Pedanius Dioscorides, noted the use of digitalis as a therapeutic agent; its application to heart failure was first recorded in print by Leonard Fuchs in 1542.1 Nevertheless, Withering was the first to systematically carry out clinical studies with the plant in a scientific manner, eliminating the superstition that had long surrounded it. Withering’s work was ground-breaking, not because of what he discovered, but how he approached its evaluation. It was the first use of the scientific method for the characterization of a pharmaceutical.

Packer, M. (2017). “Activation and inhibition of sodium-hydrogen exchanger is a mechanism that links the pathophysiology and treatment of diabetes mellitus with that of heart failure.” Circulation 136(16): 1548-1559.

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The mechanisms underlying the progression of diabetes mellitus and heart failure are closely intertwined, such that worsening of one condition is frequently accompanied by worsening of the other; the degree of clinical acceleration is marked when the 2 coexist. Activation of the sodium-hydrogen exchanger in the heart and vasculature (NHE1 isoform) and the kidneys (NHE3 isoform) may serve as a common mechanism that links both disorders and may underlie their interplay. Insulin insensitivity and adipokine abnormalities (the hallmarks of type 2 diabetes mellitus) are characteristic features of heart failure; conversely, neurohormonal systems activated in heart failure (norepinephrine, angiotensin II, aldosterone, and neprilysin) impair insulin sensitivity and contribute to microvascular disease in diabetes mellitus. Each of these neurohormonal derangements may act through increased activity of both NHE1 and NHE3. Drugs used to treat diabetes mellitus may favorably affect the pathophysiological mechanisms of heart failure by inhibiting either or both NHE isoforms, and drugs used to treat heart failure may have beneficial effects on glucose tolerance and the complications of diabetes mellitus by interfering with the actions of NHE1 and NHE3. The efficacy of NHE inhibitors on the risk of cardiovascular events may be enhanced when heart failure and glucose intolerance coexist and may be attenuated when drugs with NHE inhibitory actions are given concomitantly. Therefore, the sodium-hydrogen exchanger may play a central role in the interplay of diabetes mellitus and heart failure, contribute to the physiological and clinical progression of both diseases, and explain certain drug-drug and drug-disease interactions that have been reported in large-scale randomized clinical trials.

Rios, A., P. Parsa, J. Eidt and G. Pearl (2017). “A novel surgical approach to symptomatic left renal vein aneurysm.” J Vasc Surg Venous Lymphat Disord 5(6): 875-877.

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Visceral venous aneurysms are uncommon and renal vein aneurysms are among the rarest in this subset. Renal vein aneurysms are frequently asymptomatic, but patients may present with flank pain or hematuria. Complications of untreated visceral venous aneurysms include thrombus formation and, very rarely, rupture. Treatment of renal vein aneurysms ranges from watchful waiting to surgical repair. We describe a patient with renal vein aneurysm presenting with recurrent pulmonary embolus with no other identifiable source. Furthermore, we propose a novel surgical treatment with complete resection of the aneurysm and reconstruction of venous return by transposing the inferior mesenteric vein to the remaining left renal vein.

Packer, M. (2017). “Heart failure with a mid-range ejection fraction: A disorder that a psychiatrist would love.” JACC Heart Fail 5(11): 805-807.

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Over the past 5 decades, cardiologists have become obsessed with the ejection fraction. The term can be found in the abstracts of more than 52,000 papers; 10s of 1,000s of additional papers refer to it in their texts. The measurement yields important prognostic information in patients without heart failure, yet the field of heart failure has been particularly consumed by its assessment. We rarely find a paper about heart failure that does not mention it, guidelines mandate its evaluation in all patients, and it has been an entry criterion for every heart failure trial over the past 30 years. Its importance seems odd, however, because ejection fraction is not related to or associated with any specific clinical feature or pathophysiological abnormality of heart failure.