Entity

Time filter

Source Type


Schwartz P.J.,University of Pavia | Schwartz P.J.,Laboratory of Cardiovascular Genetics | Schwartz P.J.,University of Cape Town | Schwartz P.J.,Stellenbosch University | Schwartz P.J.,King Saud University
Pharmacology and Therapeutics | Year: 2011

The congenital long QT syndrome (LQTS) is a familial disorder characterized by a prolongation of the QT interval on the ECG and occurrence of life-threatening cardiac arrhythmias especially, but not only, under conditions of increased sympathetic activity. Symptomatic untreated patients are at high risk for sudden cardiac death. Twelve LQTS genes have been identified and most of them encode cardiac ion channels. Very effective therapies are available and in carefully treated patients mortality is around 0.5-1% over 20 years. The initial treatment should always involve β-blockers, with propranolol and nadolol being the two most effective ones. With few exceptions all mutation carriers should be treated because of the risk of sudden death during the first cardiac event. Approximately 20% of patients continue to have syncope despite the β-blockers and the most rationale next level of therapy is represented by Left Cardiac Sympathetic Denervation (LCSD), which is highly effective and can complement any other therapy. One important limitation of LCSD is that, without valid reasons, it is available only in a few selected centers. Whenever syncope recurs despite LCSD, or whenever an aborted cardiac arrest has occurred, it becomes logical to resort to the implantation of a cardioverter defibrillator (ICD). The latter, however, is burdened by a high rate (31%) of adverse events including severe ones such as endocarditis, inappropriate shocks, and by the need of frequent battery replacements. A scoring system, based on simple clinical variables, can identify the patients more and less likely to benefit from ICD implantation. © 2011 Elsevier Inc. Source


De Ferrari G.M.,Fondazione IRCCS Policlinico S. Matteo | Schwartz P.J.,Fondazione IRCCS Policlinico S. Matteo | Schwartz P.J.,University of Pavia | Schwartz P.J.,Laboratory of Cardiovascular Genetics | And 2 more authors.
Heart Failure Reviews | Year: 2011

Vagus nerve stimulation was performed experimentally for the first time more than 150 years ago. In the 1980s and 1990s, vagus nerve stimulation was shown, both in the anesthetized and in the conscious animal, to exert marked antiarrhythmic effects, particularly during acute myocardial ischemia. There is a strong rationale for a beneficial effect of augmented vagal activity in the setting of chronic heart failure. Studies in experimental models of heart failure showed that chronic vagus nerve stimulation exerts beneficial effects on left ventricular function and on survival. Vagus nerve stimulation is approved in man for refractory epilepsy and depression. The first-in-man study performed in 32 patients with chronic heart failure suggests that vagus nerve stimulation was safe and well tolerated. Six months of open-label treatment was associated with significant improvements (P < 0.001) in NYHA class, quality of life, 6-min walk test, LV ejection fraction (from 22 ± 7 to 29 ± 8%), and LV systolic volumes (P = 0.02). These improvements were maintained at 1 year. Mechanisms of action may include the following: heart rate, anti-adrenergic, anti-apoptotic, and anti-inflammatory effects as well as an increase in nitric oxide. Controlled clinical trials will start soon to assess whether vagus nerve stimulation can indeed represent a new non-pharmacological approach for the treatment of symptomatic heart failure. © 2010 Springer Science+Business Media, LLC. Source


Schwartz P.J.,Fondazione IRCCS Policlinico S. Matteo | Schwartz P.J.,University of Pavia | Schwartz P.J.,Laboratory of Cardiovascular Genetics | Schwartz P.J.,University of Cape Town | And 2 more authors.
Heart Failure Reviews | Year: 2011

Sympathetic-parasympathetic interaction plays a major role in the evolution and outcome of many cardiovascular disorders. Nonetheless, a thorough understanding of this relationship and of its potential implications for prognosis and management still escapes many cardiologists. This article reviews the background of sympathetic-parasympathetic interactions focusing on the best direct evidence available, namely direct neural recordings of the activity of single vagal and sympathetic fibers directed to the heart. It examines indirect but highly reliable markers of this interaction as they can be studied in the clinical setting of ischemic heart disease and of heart failure, focusing primarily on the experimental and clinical studies of baroreflex sensitivity. It concludes by drawing inferences likely to lead to a novel approach to the management of heart failure, resulting from the knowledge gained about the vagal control of the heart and based on electrical vagal stimulation. © 2010 Springer Science+Business Media, LLC. Source


Schwartz P.J.,University of Pavia | Schwartz P.J.,Laboratory of Cardiovascular Genetics | Schwartz P.J.,University of Cape Town | Schwartz P.J.,King Saud University
Current Opinion in Cardiology | Year: 2011

The initial observations with chronic vagal stimulation in man, though limited by very small numbers, are very encouraging and seem to open new paths, or perhaps avenues, for the management of symptomatic heart failure. This transition between experimental and clinical approaches represents an exciting example of translational research. © 2010 Wolters Kluwer Health. Source


De Ferrari G.M.,Fondazione IRCCS Policlinico San Matteo | Crijns H.J.G.M.,Maastricht University | Borggrefe M.,University of Mannheim | Smid J.,Otto Von Guericke University of Magdeburg | And 13 more authors.
European Heart Journal | Year: 2011

Aims In chronic heart failure (CHF), reduced vagal activity correlates with increased mortality and acute decompensation. Experimentally, chronic vagus nerve stimulation (VNS) improved left ventricular (LV) function and survival; clinically, it is used for the treatment of drug-refractory epilepsy. We assessed safety and tolerability of chronic VNS in symptomatic CHF patients, using a novel implantable nerve stimulation system. The secondary goal was to obtain preliminary data on clinical efficacy. Methods and resultsThis multi-centre, open-label phase II, two-staged study (8-patient feasibility phase plus 24-patient safety and tolerability phase) enrolled 32 New York Heart Association (NYHA) class IIIV patients [age 56 ± 11 years, LV ejection fraction (LVEF) 23 ± 8]. Right cervical VNS with CardioFit (BioControl Medical) implantable system started 24 weeks after implant, slowly raising intensity; patients were followed 3 and 6 months thereafter with optional 1-year follow-up. Overall, 26 serious adverse events (SAEs) occurred in 13 of 32 patients (40.6), including three deaths and two clearly device-related AEs (post-operative pulmonary oedema, need of surgical revision). Expected non-serious device-related AEs (cough, dysphonia, and stimulation-related pain) occurred early but were reduced and disappeared after stimulation intensity adjustment. There were significant improvements (P < 0.001) in NYHA class quality of life, 6-minute walk test (from 411 ± 76 to 471 ± 111 m), LVEF (from 22 ± 7 to 29 ± 8), and LV systolic volumes (P 0.02). These improvements were maintained at 1 year. ConclusionsThis open-label study shows that chronic VNS in CHF patients with severe systolic dysfunction may be safe and tolerable and may improve quality of life and LV function. A controlled clinical trial appears warranted. © 2011 The Author. Source

Discover hidden collaborations