Reduction of Lipid-Core Burden Index in Nonculprit Lesions at Follow-Up after ST-Elevation Myocardial Infarction: A Randomized Study of Bioresorbable Vascular Scaffold versus Optimal Medical Therapy.

BACKGROUND: Non-flow-limiting nonculprit lesions (NCL) that contain a large lipid-rich necrotic core (nonculprit lipid-rich plaques (NC-LRP)) are most likely to cause recurrent acute coronary syndrome after ST-elevation myocardial infarction (STEMI). Near-infrared spectroscopy (NIRS) detects LRPs using the maximum 4 mm lipid-core burden index (maxLCBI4 mm). Few data are available regarding NIRS-guided therapy of these NC-LRPs, which are a potential target for preventive stenting. Bioresorbable vascular scaffold (BVS) provides local drug delivery and could facilitate plaque passivation after resorption. This study sought to assess the safety of BVS implantation in NC-LRPs and its efficacy in reducing maxLCBI4 mm at 2-year follow-up after STEMI. METHODS AND RESULTS: In total, 33 non-flow-limiting NCLs from 29 STEMI patients were included in this study. Of these, 15 were LRPs and were randomly assigned to either the BVS + optimal medical therapy (OMT) arm (group 1; N = 7) or the OMT arm (group 2; N = 8). At baseline, there were no differences in plaque characteristics between groups (fractional flow reserve: 0.85 ± 0.04 vs. 0.89 ± 0.06; diameter stenosis (DS): 43.4 ± 8 vs. 40.1 ± 10.7%; plaque burden 54.98 ± 5.8 vs. 49.76 ± 8.31%; and maxLCBI4 mm 402 [348; 564] vs. 373 [298; 516]; p=NS for all comparisons between groups 1 and 2, respectively). Seven BVSs were implanted 3 ± 1 days after STEMI in six patients, without complications. At angiographic follow-up (712 [657; 740] days), a significant and similar reduction of maxLCBI4 mm was observed in both groups, with a median change of 306 [257; 377] in group 1 vs. 300 [278; 346] in group 2 (p=0.44). DS was significantly lower in group 1 vs. group 2 (19.8 ± 7 vs. 41.7 ± 13%, p=0.003), while plaque burden remained unchanged in both groups. Overall survival was 100%, target lesion failure was 13%, and stent thrombosis was 0%. CONCLUSIONS: BVS + OMT and OMT appear as similarly safe and effective in reducing maxLCBI4mm in NC-LRPs at 2-year follow-up after STEMI.

Usefulness of tissue Doppler imaging to evaluate pulmonary capillary wedge pressure during exercise in patients with reduced left ventricular ejection fraction.

The early diastolic transmitral velocity/tissue Doppler imaging mitral annular early diastolic velocity (E/e') ratio is used to estimate left ventricular (LV) filling pressures at rest. However, there are only limited data that validate its use during exercise. Accordingly, the aim of this study was to test the ability of E/e' to estimate pulmonary capillary wedge pressure (PCWP) during symptom-limited exercise in patients with LV systolic dysfunction. Forty patients with severe LV dysfunction and heart failure symptoms (54 ± 12 years, 28 men) underwent simultaneous Doppler assessment of E/e' and right-sided cardiac catheterization at rest and during a symptom-limited exercise test, at steady state levels of 30%, 60%, and 90% of their maximal exercise capacity. During exercise, all 40 patients successfully completed stage 1, yielding 40 pairs of data for comparison. Eighteen patients also successfully completed stage 2, and 5 patients also made it through stage 3, yielding 23 additional data pairs. In total, there were thus 63 pairs of data available during exercise. With exercise, heart rate increased from 77 ± 14 to 112 ± 21 beats/min. Septal E/e' at rest correlated well with PCWP at rest (r = 0.75, p <0.01). PCWP at rest also correlated with resting mitral deceleration time (r = 0.32, p <0.01) and with the transmitral E/A ratio (r = 0.74, p <0.01). During exercise, the correlation between septal E/e' and PCWP was weaker (r = 0.57, p <0.01) and was shifted to the right. This rightward shift was observed in patients with both separated or merged E and A velocities. In conclusion, in patients with severe LV dysfunction, although E/e' allows accurate estimation of PCWP at rest, it appears less reliable for estimating LV filing pressure during exercise.

Recovery after balloon aortic valvuloplasty in patients with aortic stenosis and impaired left ventricular function: predictors and prognostic implications.

AIMS: The aim of this study was to evaluate predictors of recovery after balloon aortic valvuloplasty (BAV) among patients with aortic stenosis and depressed left ventricular ejection fraction (LVEF). Predictors for recovery after BAV are not clearly defined. B-type natriuretic peptide (BNP) predicts outcome after surgical and transcatheter aortic valve replacement. METHODS AND RESULTS: Among 151 consecutive patients treated in our institution by BAV, a total of 59 with poor LVEF underwent an echocardiography at 1 month. In these 59 patients, LVEF significantly improved in 22 patients (group 1) from 27 ± 5% to 45 ± 6% (P<.0001) and remained unchanged in 37 patients (group 2) from 29 ± 8% to 30 ± 11% (P=NS). BNP plasma levels at 24 hours only decreased in group 1 from 2170 ± 967 pg/mL to 1208 ± 662 pg/mL (P=.001). By multivariate analysis, BNP reduction >300 pg/mL was the strongest independent predictor of LVEF improvement at 30 days (hazard ratio, 5.459; 95% confidence interval, 1.580-18.860; P=.007). Kaplan-Meier analysis showed that 1-year survival after BAV was significantly higher in patients of group 1 than in group 2 (95 ± 4% vs 51 ± 8%, respectively; P=.02). CONCLUSIONS: BAV in patients with poor left ventricular function resulted in LVEF improvement at 30 days in 37% of cases, which was detected by a reduction of BNP levels already seen at 24 hours. Survival at 1 year was significantly higher in patients with such an improved LVEF after BAV.

Impact of frailty scores on outcome of octogenarian patients undergoing transcatheter aortic valve implantation.

BACKGROUND: For selected patients with symptomatic aortic stenosis, transcatheter aortic valve implantation (TAVI) is an alternative to surgical aortic valve replacement (AVR). In addition to co-morbidities, frailty has to be taken into account in the decision-making process. Criteria for patient selection, according to current guidelines, include EuroSCORE and STS score but frailty is not easy to quantify. ISAR (Identification of Seniors At Risk) detects seniors at risk for adverse health outcome after an emergency visit and SHERPA (Score Hospitalier d'Evaluation du Risque de Perte d'Autonomie) assesses the risk of functional decline after hospitalization. OBJECTIVES: The aim of the present study was to evaluate the impact of ISAR and SHERPA scores in the prediction of patient outcome afterTAVI. METHODS AND RESULTS: A prospective cohort of 30 consecutive octogenarian patients (16 males, 86 +/- 3 y, EuroSCORE 34 +/- 12%) underwent a transfemoral TAVI and a complete geriatric assessment in our institution. Survival at one year was 73%. The ISAR score was similar between both groups (3.1 +/- 1 vs. 3.6 +/- 1; P = 0.10) but the SHERPA score was significantly higher in non-survivors (7.8 +/- 1.6) than among survivors (4.9 +/- 2.4; P = 0.001). With multivariate analysis, SHERPA score and BMI were independent predictors of 1-year mortality. Kaplan-Meier analysis showed that 1-year survival was significantly lower in patients with than in those without a SHERPA score > 7 (40 vs. 89%; P = 0.004). CONCLUSIONS: The result of this study showed that SHERPA score predicts 1-year survival after transfemoral TAVI and could be considered as a useful frailty score in patient selection.

A critical review on telemonitoring in heart failure.

Morbidity and mortality remain high in heart failure despite considerable progress achieved with medical therapy and electrical devices. A multidisciplinary approach is actually strongly recommended. In order to provide optimal care to the ever-growing population of patients with heart failure, telemonitoring has been proposed as a modality to improve usual care. The aim of this review is to provide an overview of the existing evidence on telemonitoring in HF. Despite two major meta-analyses with favourable results, two recent, large, multicentre, randomized controlled trials, one with a sophisticated technical remote telemonitoring approach (TIM-HF) in stable chronic HF and the other with a comprehensive telephone-based interactive voice-response monitoring (Tele-HF) in patients recently hospitalized for heart failure, have been performed and both failed to demonstrate a clinical benefit for telemonitoring. Newer technologies or other modalities, such as collaboration between a general practitioner and a heart failure clinic facilitated by telemonitoring should be further evaluated. Dedicated telemonitoring for heart failure may be a practical adjunct in selective centres and patients, on top of usual care, including education and a multidisciplinary approach. However, prior to being accepted as a standard of care, more evidence from large, randomized clinical trials is required.

Exercise capacity in patients supported with rotary blood pumps is improved by a spontaneous increase of pump flow at constant pump speed and by a rise in native cardiac output.

Exercise capacity is improved in patients supported with continuous flow rotary blood pumps (RP). The aim of this study was to investigate the mechanisms underlying this improvement. Ten patients implanted with a RP underwent cardiopulmonary exercise testing (CPET) at 6 months after surgery with hemodynamic and metabolic measurements (RP group). A group of 10 matched heart failure patients were extracted from our heart transplant database, and the results of their last CPET before transplantation were used for comparison (heart failure [HF] group). Peak VO(2) was significantly higher in RP than in HF patients (15.8 ± 6.2 vs. 10.9 ± 3 mL O(2)/kg.min) reaching 52 ± 16% of their predicted peak VO(2). The total output measured by a Swan-Ganz catheter increased from 5.6 ± 1.6 to 9.2 ± 1.8 L/min in the RP group and was significantly higher at rest and at peak exercise than in the HF group, whose output increased from 3.5 ± 0.4 to 5.6 ± 1.6 L/min. In the RP group, the estimated pump flow increased from 5.3 ± 0.4 to 6.2 ± 0.8, whereas the native cardiac output increased from 0.0 ± 0.5 to 3 ± 1.7 L/min. Cardiac output at peak exercise was inversely correlated with age (r = -0.86, P = 0.001) and mean pulmonary artery pressure (r = -0.75, P = 0.012). Maximal exercise capacity is improved in patients supported by RP as compared to matched HF patients and reaches about 50% of the expected values. Both a spontaneous increase of pump flow at constant pump speed and an increase of the native cardiac output contribute to total flow elevation. These findings may suggest that an automatic pump speed adaptation during exercise would further improve the exercise capacity. This hypothesis should be examined.

Endothelium-dependent and endothelium-independent vasodilator response of left and right internal mammary and internal thoracic arteries used as a composite Y-graft.

OBJECTIVE: The manner in which a blood vessel is for used as a coronary graft may be important in maintaining a viable and functional endothelial lining. Composite internal thoracic arteries (ITAs) in a Y-graft configuration are characterized by the connection of an in situ left ITA with preserved innervation and lymphatics and of a free semi-skeletonized right ITA. METHODS: To determine whether endothelial function differs between left and right ITA segments in a Y-graft configuration, 11 patients were studied 3 years after surgery. The endothelium-dependent vasodilator substance P was selectively infused (1.4-22.4 pmol min⁻¹ in doubling dose increments) in the ostium of ITA Y-grafts. A maximal endothelium-independent vasodilatory response was then obtained by intragraft infusion of 2mg isosorbide dinitrate (ISDN). Biplane angiograms obtained at 3-min intervals using an automated contrast injection system with fixed preset volume and pressure parameters were analyzed off-line using a quantitative analysis system (CAAS, Pie Medical). RESULTS: A similar dose-dependent vasodilatory response to substance P was observed in the left and in the right ITA. No difference in maximal endothelium-dependent response to substance P (7.4 ± 4.3% in the left ITA and 8.1 ± 5.3% in the right ITA) or in maximal endothelium-independent response to ISDN (12.2 ± 4.4% in the left ITA and 10.6 ± 8.1% in the right ITA) was observed. CONCLUSIONS: The endothelium-dependent and the endothelium-independent vasodilator capacity of the two branches of a Y-graft ITA configuration appear similar 3 years after bypass surgery. This suggests that the preservation of the ITA pedicle does not significantly affect basal vasomotor tone, long-term endothelial function, or vasodilator reserve.

Tako-tsubo syndrome following nortriptyline overdose.

BACKGROUND: Tako-tsubo syndrome (TTS) refers to the apical ballooning of the left ventricle observed when angiographic ventriculography is performed in patients presenting with electrocardiographic changes suggestive of acute coronary syndrome (new transient ST-segment deviation (>0.05 mV) or T-wave inversion (>0.2 mV)), mild elevation of cardiac markers, but normal coronary arteries at the angiogram. CASE REPORT: A 54-year-old woman developed the characteristic features of TTS 44 hours following nortriptyline overdose. The admission ECG showed increased QRS duration rapidly reversible after sodium bicarbonate infusion. There was a minimal increase in troponin I level. The ECG performed at the time of chest pain revealed deeply negative T waves in leads I, II, III, aVF, V1 to V6 and remained abnormal at 5 weeks follow-up. In contrast, a complete recovery of left ventricular function was observed within one week. DISCUSSION: The pathophysiology of TTS, a variant of myocardial stunning, is still incompletely understood but could be related to sympathetic overstimulation. The possibility of TTS following toxic exposure is discussed.

Allosensitization in bridge to transplant Novacor left ventricular assist device patients: analysis of long-term outcomes with regard to acute rejection and chronic allograft vasculopathy.

BACKGROUND: The true relevance of allosensitization in patients benefiting from left ventricular assist device (LVAD) as bridge to transplant (BTT) is still debated. Available registry data referred to numerous devices precluding LVAD-specific analysis. Therefore, we studied all patients with Novacor LVAD prior to transplantation. METHODS: From 1985 to 2006, 37 Novacor LVADs were implanted as BTT, with 30 patients surviving to transplantation (81%). Post-LVAD sensitization was determined for anti-HLA-class I and class II IgGs. Study endpoints were overall survival and/or graft loss, > or =3A cellular rejection and chronic allograft vasculopathy (CAV). The results from LVAD patients were compared to non-LVAD primary heart transplant recipients (n=318). RESULTS: After LVAD insertion, 5 out of 27 patients available for analysis developed anti-HLA antibodies (18.5%). The mean anti-HLA titer after Novacor LVAD implantation was 14% [SD 31]. Actuarial 5- and 10-year patient/graft survival for LVAD and non-LVAD transplant recipients were 73% and 55%, and 70% and 55%, respectively (p=NS). Overall prevalence of rejection > or =3A was 23.3 % (LVAD group) and 18.9% (non-LVAD group) (p=NS). At follow-up, the respective incidence of CAV was 8% (LVAD group) and 32.4% (non-LVAD group) (p<0.01). However, mean follow-up was significantly different for LVAD and non-LVAD patients, 46 vs 90 months (p<0.001). CONCLUSION: In this study, allosensitization occurred infrequently after Novacor LVAD implantation. Secondly, analysis of outcome variables shows that Novacor-LVAD BTT patients can anticipate similar survival to non-LVAD patients, thus minimizing the impact of allosensitization after LVAD implantation.

Superiority of big endothelin-1 and endothelin-1 over natriuretic peptides in predicting survival in severe congestive heart failure: a 7-year follow-up study.

BACKGROUND: Plasma concentrations of atrial and brain natriuretic peptides (ANP, BNP), of their N-terminal pro-peptides, of endothelin-1 (ET-1), and big endothelin-1 (big ET-1) have diagnostic and prognostic significance in congestive heart failure (CHF). However, their respective values as a predictor of survival remain controversial and have never been directly compared in severe CHF. METHODS AND RESULTS: We analyzed, in 47 patients with severe CHF (New York Heart Association [NYHA] class III to IV; age 66 +/- 8 years, ejection fraction 20 +/- 6%), the prognostic performance of a panel of neurohormones and assays (N-terminal pro-ANP 1-25, 68-98 by radioimmunoassay [RIA], and 1-98 by enzyme-linked immunosorbent assay [ELISA], BNP by RIA and immunoradiometric assay [IRMA], N-terminal pro-BNP by Elisa, ET-1 by RIA, and big ET-1 by RIA and Elisa. Data were compared with 40 patients with mild to moderate CHF [NYHA I-II] and 30 healthy subjects. After a follow-up of 81 +/- 15 months, there were 34 deaths and 1 heart transplant. All neurohormones were significantly higher at baseline in patients with severe than in mild to moderate CHF or healthy subjects (all P < .001). Although all neurohormones but BNP IRMA were significant predictors of survival in univariate analysis, only big ET-1 RIA and ET-1 were independent predictors of survival (improvement chi(2): 7.5 and 4.6, P < .01 and P < .05). Using medians as cutpoints of big ET-1 RIA and ET-1, 2 severe CHF populations were defined with a different outcome (5-year survival: 55 versus 18%, P < .01). CONCLUSIONS: Big ET-1 and ET-1 are strong independent predictors of survival in patients with severe CHF and better for this purpose than natriuretic peptides or their pro-peptides. These markers allow easily to identify a population with a very high risk mortality eligible for more aggressive therapies.

Beneficial neurohormonal profile of spironolactone in severe congestive heart failure: results from the RALES neurohormonal substudy.

OBJECTIVES: We sought to evaluate the effects of spironolactone on neurohormonal factors in patients with severe congestive heart failure (CHF). BACKGROUND: In the Randomized ALdactone Evaluation Study (RALES), spironolactone, an aldosterone receptor antagonist, significantly reduced mortality in patients with severe CHF. However, the mechanism of action and neurohormonal impact of this therapy remain to be clarified. METHODS: The effects of spironolactone (25 mg/day; n = 54) or placebo (n = 53) on plasma concentrations of the N-terminal portion of atrial natriuretic factor (N-proANF), brain natriuretic peptide (BNP), endothelin-1 (ET-1), norepinephrine (NE), angiotensin II (AII), and aldosterone were assessed in a subgroup of 107 patients (New York Heart Association functional class III to IV; mean ejection fraction 25%) at study entry and at three and six months. RESULTS: Compared with the placebo group, plasma levels of BNP (-23% at 3 and 6 months; p = 0.004 and p = 0.05, respectively) and N-proANF (-19% at 3 months, p = 0.03; -16% at 6 months, p = 0.11) were decreased after spironolactone treatment. Over time, spironolactone did not modify the plasma levels of NE and ET-1. Angiotensin II increased significantly in the spironolactone group at three and six months (p = 0.003 and p = 0.001, respectively). As expected, a significant increase in aldosterone levels was observed over time in the spironolactone group (p = 0.001). CONCLUSIONS: Spironolactone administration in patients with CHF has opposite effects on circulating levels of natriuretic peptides (which decrease) and aldosterone and AII (which increase). The reduction in natriuretic peptides might be related to changes in left ventricular diastolic filling pressure and/or compliance, whereas the increase in AII and aldosterone probably reflects activated feedback mechanisms. Further studies are needed to link these changes to the beneficial effects on survival and to determine whether the addition of an AII antagonist could be useful in this setting.

Randomized comparison of primary stenting and provisional balloon angioplasty guided by flow velocity measurement

Background—Coronary stenting improves outcomes compared with balloon angioplasty, but it is costly and may haveother disadvantages. Limiting stent use to patients with a suboptimal result after angioplasty (provisional angioplasty) may be as effective and less expensive.Methods and Results—To analyze the cost-effectiveness of provisional angioplasty, patients scheduled for single-vessel angioplasty were first randomized to receive primary stenting (97 patients) or balloon angioplasty guided by Doppler flow velocity and angiography (523 patients). Patients in the latter group were further randomized after optimization to either additional stenting or termination of the procedure to further investigate what is “optimal.” An optimal result wasdefined as a flow reserve 2.5 and a diameter tenosis 36%. Bailout stenting was needed in 129 patients (25%) who were randomized to balloon angioplasty, and an optimal result was obtained in 184 of the 523 patients (35%). There was no significant difference in event-free survival at 1 year between primary stenting (86.6%) and provisional angioplasty (85.6%). Costs after 1 year were significantly higher for provisional angioplasty (EUR 6573 versus EUR 5885; (P50.014). Results after the second randomization showed that stenting was also more effective after optimal balloon angioplasty (1-year event free survival, 93.5% versus 84.1%; P50.066). Conclusions—After 1 year of follow-up, provisional angioplasty was more expensive and without clinical benefit. The beneficial value of stenting is not limited to patients with a suboptimal result after balloon angioplasty.