Cardiac contractility modulation in heart failure patients: Randomized comparison of signal delivery through one vs. two ventricular leads.

BACKGROUND: Cardiac contractility modulation (CCM) is an electrical stimulation treatment for symptomatic heart failure (HF) patients. The procedure involves implantation of two ventricular leads for delivery of CCM impulses. The purpose of this study is to compare the efficacy and safety of CCM when the signal is delivered through one vs. two ventricular leads. METHODS: This prospective blinded randomized trial enrolled 48 patients. Eligible subjects had symptoms despite optimal HF medications, left ventricular ejection fraction <40% and peakVO2≥9ml O2/kg/min. All patients received a CCM system with two ventricular leads, and were randomized to CCM active through both or just one ventricular lead; 25 patients were randomized to receive signal delivery through two leads (Group A) and 23 patients to signal delivery through one lead (Group B). The study compared the mean changes from baseline to 6 months follow-up in peakVO2, New York Heart Association (NYHA) classification, and quality of life (by MLWHFQ). RESULTS: Following 6 months, similar and significant (p<0.05) improvements from baseline in NYHA (-0.7±0.5 vs. -0.9±0.7) and MLWHFQ (-14±20 vs. -16±22) were observed in Group A and in Group B. PeakVO2 showed improvement trends in both groups (0.34±1.52 vs. 0.10±2.21ml/kg/min; p=ns). No patient died. Serious adverse event rates (20 events in 10 subjects) were not different between groups. No statistically significant difference was found in any of the study endpoints. CONCLUSIONS: The efficacy and safety of CCM in this study were similar when the signal was delivered through either one or two ventricular leads. These results support the potential use of a single ventricular lead for delivery of CCM.

Collaterals and the recovery of left ventricular function after recanalization of a chronic total coronary occlusion.

BACKGROUND: A good collateral function in patients with regional myocardial dysfunction may indicate viability with the potential for left ventricular (LV) recovery after revascularization of a chronic total coronary occlusion (CTO). METHODS: A CTO (duration > 2 weeks) was successfully recanalized in 126 patients. During this procedure, the collateral function was assessed before the first balloon inflation by intracoronary Doppler and pressure wires. Collateral function indexes were calculated. Left ventricular function was assessed by the LV ejection fraction (LVEF) and the wall motion severity index (WMSI [SD/chords]). A repeat angiography was available in 119 patients after 4.9 +/- 1.4 m. An improvement of WMSI > or =1 SD/chord was considered significant. RESULTS: Left ventricular function was normal in 42%, regional dysfunction with LVEF > or = 0.60 was observed in 16%, and regional dysfunction with LVEF < 0.60 in 42%. The former had a better collateral function than patients with LV dysfunction. In 39% of patients with LV dysfunction, a significant myocardial recovery was observed at follow-up. The collateral function was similar in patients with and without recovery. However, patients with recovery had a lower peripheral resistance as an indicator of a better preserved microvascular integrity. CONCLUSIONS: Recovery of impaired LV function after revascularization of a CTO is not directly related to the quality of collateral function, as collateral development does not appear to require the presence of viable myocardium. However, a preserved microvascular integrity may be of relevance for myocardial recovery.

Sirolimus-eluting stents for the prevention of restenosis in a worst-case scenario of diffuse and recurrent in-stent restenosis.

For recurrent in-stent restenosis (ISR), surgical revascularization or brachytherapy is still the principal therapeutic options. The present investigation explores the efficacy of a sirolimus-eluting stent to prevent restenosis in these lesions with a high risk of recurrence. In 22 consecutive patients with a recurrent and diffuse ISR, a sirolimus-eluting stent was implanted to cover the restenotic lesion. All patients were followed clinically for at least 1 year and underwent a repeat angiography after 7 months. A quantitative coronary angiographic analysis was done. The target vessel failure was 14% in the sirolimus-eluting stent group, with an angiographic late loss of only 0.39 +/- 0.54. No subacute stent thrombosis was observed, and the 1-year event-free survival was 86%. The three cases with restenosis were all focal and could be successfully treated by additional drug-eluting stent implantation. This study showed the efficacy of a sirolimus-eluting stent for the prevention of restenosis in a worst-case scenario of recurrent and diffuse ISR. The observed restenosis rate is lower than that reported after brachytherapy and suggests that sirolimus-eluting stents are a promising treatment option for ISR.

Regression of collateral function after recanalization of chronic total coronary occlusions: a serial assessment by intracoronary pressure and Doppler recordings.

BACKGROUND: Collaterals can maintain myocardial function or preserve viability in chronic total coronary occlusions (CTOs). It is unknown whether and to what extent collaterals regress after successful recanalization of a CTO. METHODS AND RESULTS: In 103 patients with successful recanalization of a CTO collateral function was assessed by intracoronary Doppler and pressure recordings before and after recanalization, and again after 5.0+/-1.3 months. Doppler (CFI) and pressure-derived collateral function indexes (CPI) and collateral (RColl) and peripheral resistance indexes (RP) were calculated. In 10 patients with reocclusion, all without myocardial infarction during follow-up, collateral function had reached a similar level as before the first recanalization. In the other 93 patients with or without restenosis, collateral function was attenuated during follow-up. CPI had decreased by 23% immediately after recanalization (P<0.001) and decreased further by another 23% at follow-up (P<0.001). The RColl increased immediately after recanalization by 82% (P<0.001) and by a further 273% at follow-up (P<0.001). In contrast, RP increased only by 22% after recanalization (P<0.001) and by an additional 12% at follow-up (P<0.05). The initial size of the collaterals but not the incidence of a restenosis influenced the collateral regression. Only 18% of patients at follow-up had collaterals with a CPI >0.30, presumably sufficient to prevent ischemia during acute occlusion. CONCLUSIONS: Collateral function regresses during long-term follow-up, especially in collaterals with a small diameter. In the majority of patients, collaterals are not readily recruitable in the case of acute occlusion. However, collaterals have the potential to recover in the case of chronic reocclusion.

Determinants of target vessel failure in chronic total coronary occlusions after stent implantation. The influence of collateral function and coronary hemodynamics.

OBJECTIVES: The goal of this study was to assess the influence of collateral function, coronary hemodynamics, and the angiographic result on the risk of target vessel failure (TVF) after recanalization of a chronic total coronary occlusion (CTO). BACKGROUND: Collaterals may have an adverse effect on TVF. METHODS: In 111 consecutive patients, a CTO (duration >2 weeks) was successfully recanalized with stent implantation. Collateral function was assessed by intracoronary Doppler flow velocity and pressure recordings distal to the occlusion. Baseline collateral function was determined before the first balloon inflation, and recruitable collateral function after stenting during a balloon reocclusion. Finally, the coronary flow velocity reserve (CFVR) and the fractional flow reserve (FFR) were measured. RESULTS: Angiographic follow-up after 5 +/- 4 months in 106 patients showed a reocclusion in 17% and a restenosis in 36%. The major determinants of TVF were the stent length (p < 0.01) and number of implanted stents (p < 0.01). No difference was observed in baseline or recruitable collateral function between patients with and without TVF; 52% of patients had a CFVR >or= 2.0, and only 18% a CFVR >or=2.5 after percutaneous transluminal coronary angioplasty, but neither cutoff-value predicted TVF. A low FFR discriminated patients with reocclusion (0.81 +/- 07 vs. 0.86 +/- 08, p < 0.05) but not with restenosis (0.87 +/- 0.06). CONCLUSIONS: This study showed that there is no relation between a well-developed collateral supply and the risk of TVF in recanalized CTOs. This was rather determined by the stented segment length. There was also no adverse effect of the frequently observed impaired CFVR on TVF, whereas a low FFR was associated with a higher risk of reocclusion.

Contribution of myoglobin-induced increases in vascular resistance to shock decompensation in experimental Crush-syndrome in anesthetized rats.

Myoglobin is known to become nephrotoxic when released in greater amounts from skeletal muscle into the general circulation during shock. The present study deals with the question as to whether a myoglobin-induced increase in vascular tone additionally contributes to the detrimental role of this protein in hypovolemic shock. Anesthetized rats were subjected to 250 mg kg x h(-1) myoglobin infused i.v. during hemorrhagic hypotension of 50 mmHg. Shock survival time was measured, as were blood flow and vascular resistance in kidney, intestine, brain, and heart, using the microsphere method. Rats subjected to only myoglobin or hemorrhage survived a period of >120 min; in contrast, rats, exposed to both myoglobin and hemorrhage died at 68 +/- 9 min. When the animals subjected to only hemorrhage and to myoglobin/ hemorrhage were compared, significantly lower values were found in the latter group with respect to blood flow in the kidney (1.7 +/- 0.1 vs. 0.2 +/- 0.05 ml x min(-1) x g(-1)), small intestine (1.0 +/- 0.1 vs. 0.5 +/- 0.1 ml x min(-1) x g(-1)), cardiac output (112 +/- 5 vs. 62 +/- 10 ml(-1) x min(-1) x kg(-1)), and significantly higher values of total peripheral vascular resistance (0.45 +/- 0.02 vs. 0.81 +/- 0.12 mmHg x min x ml(-1) x kg) at 50 min of hypotension. It is assumed that these effects of myoglobin are induced by its ability to scavenge endogenous nitric oxide, because a modified, non-nitrosylable myoglobin was unable to induce such effects. The results support the view that a pathological release of myoglobin into the general circulation causes increases in vascular resistance of vital organs that may contribute to decompensation of tissue supply when occurring in hypovolemic shock.