Cardiology

Roberts, W. C., I. Kale and C. S. Roberts (2020). “Perforation of a Stenotic Congenitally Bicuspid Aortic Valve Cusp by Heavy Calcium in the Other Cusp.” Am J Cardiol 125(2): 299-301.

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On occasion in patients with stenotic congenitally bicuspid aortic valves (BAVs), the quantity of calcium in one of the cusps is considerably greater than in the other cusp. We examined operatively excised stenotic congenitally BAVs in 630 patients having isolated aortic valve replacement (No other cardiac valve was replaced, and none had had infective endocarditis.) Of the 630 valves, 3 contained a perforation in the mildly calcified cusp due to a large calcific “spur” extending across the orifice from a heavily calcified cusp. In conclusion, heavy calcific deposits in 1 of 2 BAVs may extend across the orifice causing a perforation in the noncalcified portion of the opposing cusp.

Roberts, W. C., N. Ather and J. M. Guileyardo (2020). “Examining Hearts Containing Left Ventricular Assist Devices at Necropsy.” Am J Cardiol 125(2): 244-250.

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There are no publications describing hearts at necropsy containing left ventricular assist devices (LVADs). The purpose was to study the relation of the LVAD cannula to the left ventricular (LV) cavity and wall. We studied the hearts at necropsy of 15 adults who had an LVAD inserted from 4 to 1,423 days (median 60) earlier. In 13 patients, the cannula had been inserted at an angle to the major longitudinal axis of the LV chamber, and in 11 patients, the orifice margin of the cannulas contacted the LV mural endocardium. In 3 patients, the LVAD cannula was inserted into the posterior wall, and, in another into the anterior wall. In the remaining 11 patients, the cannula had been inserted into the LV apex. Despite the insertion of the cannulas into the LV apex, the direction of the insertion was not into the longitudinal axis of the LV cavity in 9 patients. These unusual insertions in some patients may have altered flow into the orifice of the cannula; in others, based on their long postoperative survival, physiologic consequences were almost certainly absent. The presence of considerable quantities of subepicardial adipose tissue and pericardial adhesions from previous cardiac procedures (mainly coronary bypass) potentially interfered with achieving proper alignment of the LVAD cannula during its insertion. Misalignment of the cannulas of the LVAD in the LV cavity appears to be rather frequent.

Packer, M., C. S. P. Lam, L. H. Lund and M. M. Redfield (2020). “Interdependence of Atrial Fibrillation and Heart Failure With a Preserved Ejection Fraction Reflects a Common Underlying Atrial and Ventricular Myopathy.” Circulation 141(1): 4-6.

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Atrial fibrillation (AF) and heart failure with a preserved ejection fraction (HFpEF) are closely intertwined disorders that afflict millions of people, many of whom are obese or have diabetes mellitus or other proinflammatory conditions. Conceivably, the convergence of AF and HFpEF might be explained by 2 distinctly different frameworks. On the one hand, it is possible that each phenotype might lead sequentially to the other (ie, the increased left ventricular [LV] filling pressure in HFpEF may cause left atrial [LA] dilatation that triggers AF, and conversely, the rapid heart rate that accompanies AF might lead to LV fibrosis, although there is little evidence to support this hypothesis). On the other hand, and more likely, the 2 disorders may be parallel manifestations of the same underlying myocardial disease, which causes AF (because it affects the LA) and HFpEF (because it afflicts the LV) . . . AF and HFpEF demonstrate an exceptionally high degree of clinical and epidemiological convergence. Regardless of which disorder presents first, both are or will soon become evident in the same patients. AF and HFpEF appear to both be manifestations of a common underlying atrial and ventricular myopathy that is triggered when a systemic inflammatory or metabolic disorder causes coronary microvascular dysfunction and fibrosis of the atrial and ventricular myocardium, a process that may be mediated or exacerbated by inflammation in the adjoining epicardial adipose tissue. (Excerpts from text, p. 4, 6; no abstract available.)

Packer, M. (2020). “Potential Role of Atrial Myopathy in the Pathogenesis of Stroke in Rheumatoid Arthritis and Psoriasis: A Conceptual Framework and Implications for Prophylaxis.” J Am Heart Assoc 9(3): e014764.

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Both rheumatoid arthritis (RA) and psoriasis are accompanied by an increased risk of stroke, which cannot be explained by an increased prevalence of traditional cardiovascular risk factors that are focused on atherosclerosis. Instead, the risk of stroke is likely to be related to an effect of systemic inflammation to promote the development of an atrial myopathy, resulting in blood stasis within the left atrium (LA), thrombus formation, and systemic thromboembolism. The systemic inflammatory process in RA and psoriasis can directly impair the integrity of the endothelium of the coronary microcirculation of the atrial myocardium. In addition, systemic inflammation can cause expansion of the epicardial adipose tissue adjacent to the LA; the secretion of proinflammatory adipocytokines from the epicardial fat depot can exaggerate the adverse structural and functional changes in the LA, leading to the atrial myopathy that provides the substrate for thromboembolic stroke. Interventions that are directed toward alleviation of the atrial myopathy and the resulting risk of thrombus formation are worthy of further evaluation in reducing the burden of cerebrovascular disease in patients with RA and psoriasis. (Excerpt from text, n.p.; no abstract available.)

Packer, M. (2020). “Interplay of AMPK/SIRT1 Activation and Sodium Influx Inhibition Mediates the Renal Benefits of SGLT2 Inhibitors in Type 2 Diabetes: a Novel Conceptual Framework.” Diabetes Obes Metab. Jan 9. [Epub ahead of print].

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Long-term treatment with SGLT2 inhibitors slows the deterioration of renal function in patients with diabetes. This benefit cannot be ascribed to an action on blood glucose, ketone utilization, uric acid or systolic blood pressure. SGLT2 inhibitors produce a striking amelioration of glomerular hyperfiltration. Although initially ascribed to an action of these drugs to inhibit proximal tubular glucose reabsorption, SGLT2 inhibitors exert renoprotective effects even in patients with meaningfully impaired levels of glomerular function that are sufficient to abolish their glycosuric actions. Instead, the reduction in intraglomerular pressures may be related to an action of SGLT2 inhibitors to interfere with the activity of sodium-hydrogen exchanger isoform 3 (NHE-3), thereby inhibiting proximal tubular sodium reabsorption and promoting tubuloglomerular feedback. Yet, experimentally, such an effect may not be sufficient to prevent renal injury. It is therefore noteworthy that the diabetic kidney exhibits an important defect in AMPK and SIRT1 signaling, which may contribute to the development of nephropathy. These enzymes exert direct effects to mute oxidative stress and inflammation, and they also stimulate autophagy, a lysosomally-mediated degradative pathway that maintains cellular homeostasis in the kidney. SGLT2 inhibitors induce both AMPK and SIRT1, and they have been shown to stimulate autophagy, thereby ameliorating cellular stress and glomerular and tubular injury. Enhanced AMPK/SIRT1 signaling may also contribute to the action of SGLT2 inhibitors to interfere with sodium transport mechanisms. The dual effects of SGLT2 inhibitors on AMPK/SIRT1 activation and renal tubular sodium transport may explain their protective effects on the kidney in type 2 diabetes.