Acute Haemodynamic and Echocardiographic Effects of Multiple Configurations of Left Ventricular Pacing Sites in Acute Myocardial Infarction: Experimental Study.

BACKGROUND: Left ventricular (LV) pacing is unsuccessful in a significant number of patients, mainly due to sub-optimal LV pacing location. Nevertheless, data about the impact of different pacing sites on LV function in ischaemic myocardium are scarce. The purpose of this study was to investigate the effect of combinations of alternative LV pacing sites on LV mechanics after experimental acute anterior myocardial infarction (AMI), in order to define the optimal configuration. METHODS: Atrioventricular epicardial pacing at alternative pacing sites was performed in 16 healthy pigs simultaneously, after experimental AMI. Standard right ventricular (RV) apical pacing was combined with: i) LV apex lateral wall; ii) LV basal posterior wall; iii) LV basal anterior wall, and; iv) LV basal anterior wall + LV basal posterior wall. Moreover the pacing configurations of, v) LV basal posterior wall + LV apex lateral wall; vi) LV basal posterior wall + LV basal anterior wall, and; vii) LV basal anterior wall + LV apex lateral wall were also investigated. Haemodynamic parameters, together with classic and novel echocardiographic indices were used, to evaluate the effect of each pacing combination. A speckle tracking technique using EchoPAC software was used. RESULTS: After AMI, the pacing combination of LV apex lateral wall and LV basal posterior wall had the most favourable effect on LV function, leading to similar haemodynamic and torsional effects with sinus rhythm (all variables p>0.05). CONCLUSIONS: In pig hearts after AMI, the combination of pacing LV apex lateral wall and LV basal posterior wall managed to maintain the LV function at a level comparable to the sinus rhythm.

Addition of cyclophosphamide and higher doses of dexamethasone do not improve outcomes of patients with AL amyloidosis treated with bortezomib.

Bortezomib, in combination with dexamethasone (VD) or with the addition of cyclophosphamide (VCD), is highly effective in patients with amyloid light-chain (AL) amyloidosis. Currently, VCD is considered as a primary regimen for patients with AL, but it is not clear whether the addition of cyclophosphamide to VD further and significantly improves efficacy, given the substantial activity of bortezomib itself. We retrospectively compared the outcomes of 101 patients with AL amyloidosis who received VD (n=59) or VCD (n=42) in two consecutive periods. Early mortality after adjustment for Mayo stage was similar. On intent to treat, a hematologic response rate was 68% for patients treated with VD and 78% for VCD (P=0.26), while complete response+very good partial response (CR+VGPR) rate was 47.5% and 35%, respectively. Higher doses of dexamethasone or twice-weekly bortezomib were not associated with significantly higher CR+VGPR rates. Organ responses occurred in similar rates between the two groups. Median survival was similar (33 vs 36 months, P=0.45) even after adjustment for Mayo stage and dose and schedule of bortezomib and dexamethasone. In conclusion, bortezomib even with low doses of dexamethasone is effective for the treatment of AL amyloidosis; higher doses of dexamethasone and addition of cyclophosphamide do not seem to have a profound effect on efficacy and survival.

Atrioventricular node modification in patients with chronic atrial fibrillation: role of morphology of RR interval variation.

BACKGROUND: This study evaluates the role of RR interval distribution pattern as an outcome predictor of radiofrequency (RF) modification of atrioventricular (AV) node in chronic atrial fibrillation (AF) and attempts to elucidate the likely mechanism of rate control. METHODS AND RESULTS: Sixty-five patients with chronic AF underwent AV node modification. The RR interval distribution pattern was derived from 24-hour ECG recordings obtained before and after the procedure. The preablation pattern was bimodal (B) in 36 patients (55%) and unimodal (U) in 29 patients (45%). After the modification procedure, the B pattern shifted to U (78%) or became modified B (22%). The mean number of RF pulses delivered and the fluoroscopy time were n=8+/-5 and 24+/-11 minutes, respectively, in patients with B pattern versus n=18+/-7 and 45+/-17 minutes in patients with U pattern (P<0.001 for both). The location of successful ablation was posteroseptal and lower midseptal in 26 patients (81%) with B pattern versus 2 (13%) with U pattern (P<0.001). Mean and maximal ventricular rates and heart rate at peak exercise were reduced after the procedure in both groups (P<0.001 for all). Long-term success rate, AV block incidence, and pacemaker implantation rate were 89%, 0%, and 8%, respectively, in patients with B pattern versus 52% (P<0.001), 21% (P=0.006), and 48% (P<0.001) in patients with U pattern. CONCLUSIONS: RF modification of the AV node is expected to be more effective, safe, and expeditious in patients with chronic AF and B RR interval distribution pattern. Posterior atrionodal input ablation may be the prevailing mechanism of rate control in these patients, whereas U-pattern patients may benefit from partial injury to the AV node.

Osteoprotegerin is a significant prognostic factor for overall survival in patients with primary systemic amyloidosis independent of the Mayo staging.

Bone metabolism has not been systematically studied in primary (AL) amyloidosis. Thus we prospectively evaluated bone remodeling indices in 102 patients with newly diagnosed AL amyloidosis, 35 healthy controls, 35 newly diagnosed myeloma and 40 monoclonal gammopathy of undetermined significance patients. Bone resorption markers (C-telopeptide of type-1 collagen, N-telopeptide of type-1 collagen) and osteoclast regulators (soluble receptor activator of nuclear factor-κB ligand (sRANKL), osteoprotegerin (OPG)) were increased in AL patients compared with controls (P<0.01), but bone formation was unaffected. Myeloma patients had increased bone resorption and decreased bone formation compared with AL patients, while sRANKL/OPG ratio was markedly decreased in AL, due to elevated OPG in AL (P<0.001). OPG correlated with N-terminal pro-brain natriuretic peptide (P<0.001) and was higher in patients with cardiac involvement (P=0.028) and advanced Mayo stage (P=0.001). OPG levels above the upper value of healthy controls was associated with shorter survival (34 versus 91 months; P=0.026), while AL patients with OPG levels in the top quartile had very short survival (12 versus 58 months; P=0.024). In Mayo stage 1 disease, OPG identified patients with poor survival (12 versus >60 months; P=0.012). We conclude that increased OPG in AL is not only a compensation to osteoclast activation but may also reflect early cardiac damage and may identify patients at increased risk of death within those with earlier Mayo stage.