Very Late Stent Thrombosis 42 Months after Implantation of Sirolimus-Eluting Stent and Discontinuation of Antiplatelet Therapy

Although safety profiles of sirolimus-eluting stents do not seem to differ in short-to-medium term from those of bare-metal stents, late stent thrombosis after deployment of drug-eluting stents has emerged as a potential safety concern in the era of high-pressure stent implantation. Here, we describe the case of a patient with acute myocardial infarction due to stent thrombosis of a sirolimus-eluting stent 42 months after stent deployment and 5 weeks after discontinuation of aspirin treatment. To the best of our knowledge, this is one of the most delayed cases of sirolimus-eluting stent thrombosis described so far. The case emphasizes the potential risk that late stent thrombosis can unpredictably occur at any time point after drug-eluting stent deployment

Selective Attenuation of Norepinephrine Release and Stress-Induced Heart Rate Increase by Partial Adenosine A1 Agonism

The release of the neurotransmitter norepinephrine (NE) is modulated by presynaptic adenosine receptors. In the present study we investigated the effect of a partial activation of this feedback mechanism. We hypothesized that partial agonism would have differential effects on NE release in isolated hearts as well as on heart rate in vivo depending on the genetic background and baseline sympathetic activity. In isolated perfused hearts of Wistar and Spontaneously Hypertensive Rats (SHR), NE release was induced by electrical stimulation under control conditions (S1), and with capadenoson 6 · 10−8 M (30 µg/l), 6 · 10−7 M (300 µg/l) or 2-chloro-N6-cyclopentyladenosine (CCPA) 10−6 M (S2). Under control conditions (S1), NE release was significantly higher in SHR hearts compared to Wistar (766+/−87 pmol/g vs. 173+/−18 pmol/g, p<0.01). Capadenoson led to a concentration-dependent decrease of the stimulation–induced NE release in SHR (S2/S1 = 0.90±0.08 with capadenoson 6 · 10−8 M, 0.54±0.02 with 6 · 10−7 M), but not in Wistar hearts (S2/S1 = 1.05±0.12 with 6 · 10−8 M, 1.03±0.09 with 6 · 10−7 M). CCPA reduced NE release to a similar degree in hearts from both strains. In vivo capadenoson did not alter resting heart rate in Wistar rats or SHR. Restraint stress induced a significantly greater increase of heart rate in SHR than in Wistar rats. Capadenoson blunted this stress-induced tachycardia by 45% in SHR, but not in Wistar rats. Using a [35S]GTPγS assay we demonstrated that capadenoson is a partial agonist compared to the full agonist CCPA (74+/−2% A1-receptor stimulation). These results suggest that partial adenosine A1-agonism dampens stress-induced tachycardia selectively in rats susceptible to strong increases in sympathetic activity, most likely due to a presynaptic attenuation of NE release

Acute Beneficial Hemodynamic Effects of a Novel 3D-Echocardiographic Optimization Protocol in Cardiac Resynchronization Therapy

Post-implantation therapies to optimize cardiac resynchronization therapy (CRT) focus on adjustments of the atrio-ventricular (AV) delay and ventricular-to-ventricular (VV) interval. However, there is little consensus on how to achieve best resynchronization with these parameters. The aim of this study was to examine a novel combination of doppler echocardiography (DE) and three-dimensional echocardiography (3DE) for individualized optimization of device based AV delays and VV intervals compared to empiric programming.25 recipients of CRT (male: 56%, mean age: 67 years) were included in this study. Ejection fraction (EF), the primary outcome parameter, and left ventricular (LV) dimensions were evaluated by 3DE before CRT (baseline), after AV delay optimization while pacing the ventricles simultaneously (empiric VV interval programming) and after individualized VV interval optimization. For AV delay optimization aortic velocity time integral (AoVTI) was examined in eight different AV delays, and the AV delay with the highest AoVTI was programmed. For individualized VV interval optimization 3DE full-volume datasets of the left ventricle were obtained and analyzed to derive a systolic dyssynchrony index (SDI), calculated from the dispersion of time to minimal regional volume for all 16 LV segments. Consecutively, SDI was evaluated in six different VV intervals (including LV or right ventricular preactivation), and the VV interval with the lowest SDI was programmed (individualized optimization).EF increased from baseline 23±7% to 30±8 (p<0.001) after AV delay optimization and to 32±8% (p<0.05) after individualized optimization with an associated decrease of end-systolic volume from a baseline of 138±60 ml to 115±42 ml (p<0.001). Moreover, individualized optimization significantly reduced SDI from a baseline of 14.3±5.5% to 6.1±2.6% (p<0.001).Compared with empiric programming of biventricular pacemakers, individualized echocardiographic optimization with the integration of 3-dimensional indices into the optimization protocol acutely improved LV systolic function and decreased ESV and can be used to select the optimal AV delay and VV interval in CRT

Baseline characteristics.

<p>Values are shown as means ± standard deviation or count (percentage).</p><p>NYHA, New York Heart Association; CMP, cardiomyopathy; ACE, Angiotensin-converting enzyme; ARB, Angiotensin receptor blocker; LV, left ventricle; SDI, systolic dyssynchrony index.</p

Echocardiographic parameters at baseline and after AV delay and VV interval optimization.

<p>SDI, systolic dyssynchrony index; AV, atrio-ventricular; VV, ventriculo-ventricular; LV, left ventricular; VTI, velocity-time integral.</p><p>Shown are means ± standard deviation.</p>†<p>p<0.001: for comparison of AV optimization vs baseline.</p>¶<p>p<0.05: for comparison of complete optimization vs AV optimization only.</p><p>*p<0.05: for comparison of complete optimization vs baseline.</p

Ventricular-to-ventricular (VV) intervals in patients with ischemic and dilated cardiomyopathy.

<p>Number of patients with simultaneous activation of left and right ventricle or sequential inter-ventricular pacing depending on ischemic or dilated cardiomyopathy.</p

Acute hemodynamic effects of 3D-echocardiography guided optimization.

<p>Hemodynamic variables for each timestep of the optimization protocol: A) systolic dyssynchrony index, B) ejection fraction, and C) left-ventricular end-diastolic and end-systolic volumes. Shown are means ± standard deviation. * p<0.05 vs. baseline values.</p