On 2014 Oct 16, Gaetano Santulli commented:

This study strongly endorses the hypothesis that counteracting neurohormonal hyperactivation represents a cornerstone for the treatment of heart failure. Remarkably, the Authors did not provide any data on the smoking status of the patients nor on catecholamine levels, which I believe would contribute compelling pathophysiological insights about the modulation of autonomic nervous system by neprilysin/angiotensin receptor inhibition. Indeed, cigarette smoking has been shown to increase catecholamine release, generating important effects on cardiovascular regulation essentially via sympathetic nervous system activation (1). Supporting this view, when examining the diabetic population (one third of the enrolled patients) no significant difference was found in the specific outcome ‘death from cardiovascular causes’. This finding could be at least in part ascribable to the autonomic neuropathy and neurovascular dysfunction described in diabetes mellitus (2). In this sense, an analysis that takes into account the duration of diabetes and therapy [i.e. insulin vs oral hypoglycemics (3)] in this population would also be interesting to the Reader.

References 1. Grassi G, Seravalle G, Calhoun DA, et al. Mechanisms responsible for sympathetic activation by cigarette smoking in humans. Circulation 1994;90:248-53. 2. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes care 2003;26:1553-79. 3. Sardu C, Marfella R, Santulli G. Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people. J Cardiovasc Transl Res. 2014 Apr;7(3):362-8.

Gaetano Santulli, MD, PhD Columbia University Medical Center, New York, NY, USA

On 2014 Oct 16, Gaetano Santulli commented:

This study strongly endorses the hypothesis that counteracting neurohormonal hyperactivation represents a cornerstone for the treatment of heart failure. Remarkably, the Authors did not provide any data on the smoking status of the patients nor on catecholamine levels, which I believe would contribute compelling pathophysiological insights about the modulation of autonomic nervous system by neprilysin/angiotensin receptor inhibition. Indeed, cigarette smoking has been shown to increase catecholamine release, generating important effects on cardiovascular regulation essentially via sympathetic nervous system activation (1). Supporting this view, when examining the diabetic population (one third of the enrolled patients) no significant difference was found in the specific outcome ‘death from cardiovascular causes’. This finding could be at least in part ascribable to the autonomic neuropathy and neurovascular dysfunction described in diabetes mellitus (2). In this sense, an analysis that takes into account the duration of diabetes and therapy [i.e. insulin vs oral hypoglycemics (3)] in this population would also be interesting to the Reader.

References 1. Grassi G, Seravalle G, Calhoun DA, et al. Mechanisms responsible for sympathetic activation by cigarette smoking in humans. Circulation 1994;90:248-53. 2. Vinik AI, Maser RE, Mitchell BD, Freeman R. Diabetic autonomic neuropathy. Diabetes care 2003;26:1553-79. 3. Sardu C, Marfella R, Santulli G. Impact of diabetes mellitus on the clinical response to cardiac resynchronization therapy in elderly people. J Cardiovasc Transl Res. 2014 Apr;7(3):362-8.

Gaetano Santulli, MD, PhD Columbia University Medical Center, New York, NY, USA