Significant increase of flow kinetic energy in "nonresponders" patients to cardiac resynchronization therapy.

BACKGROUNDS: It's still unclear if different patterns of intraventricular flow dynamics may be detected in patients nonresponders to cardiac resynchronization therapy (CRT) as compared to responders ones. Aim of this study was to evaluate the characteristics of left ventricular (LV) flow dynamics 6-months after CRT to identify Echo-particle imaging velocity (PIV) patterns were more frequently detected in nonresponders patients. METHODS: Thirty-two patients with dilated cardiomyopathy, undergoing CRT, were enrolled in this study. All patients underwent 2D and 3D echo and fluid dynamics assessment 6 months after CRT, during active CRT (CRT-ON) and during a temporarily discontinued state (CRT-OFF). LV volumes systolic and diastolic volumes (LVESV and LVEDV), ejection fraction (LVEF), global longitudinal strain (GLS), systolic dyssynchrony index (SDI), and several geometrical and functional Echo-PIV-derived parameters were calculated. Patients were divided in two groups: "responders" to CRT (decrease in LVESV>15% 6 months after CRT) and "nonresponders." RESULTS: During CRT-OFF, LVEF, GLS were lower, while SDI and LVESV were higher in nonresponders group (P=.030, P=.051, P=.035, and P=.025, respectively). Energy dissipation, vortex area, and vorticity fluctuation were higher in "nonresponders" patients during CRT-OFF (P=.038, P=.054, and P=.035, respectively). During CRT-ON, energy dissipation, vortex area, and vorticity fluctuation further increase in nonresponders patients (P=.020, P=.038, and P=.030, respectively) with a concomitant worsening of SDI (P=.045). CONCLUSION: Our data show a significant worsening in flow-derived parameters in CRT "nonresponders" patients as compared with responders. Further larger longitudinal studies are necessary to assess whether these more chaotic intraventricular flow-patterns may contribute to a persistent adverse remodeling observed in this subset of patients.

Plasma adrenomedullin and endothelin-1 concentration during low-dose dobutamine infusion: Relationship between pulmonary uptake and pulmonary vascular pressure/flow characteristics.

AIM: To study the role of endothelin (ET-1) and adrenomedullin (AM) on pulmonary vascular pressure/flow characteristic (pulmonary arterial pressure/cardiac output (Pap/CO)) during low-dose dobutamine infusion. METHODS: Case control study of 14 patients (12 men, 2 women) with severe lung disease (chronic obstructive pulmonary disease, COPD n=5; cystic fibrosis, CF n=9) and 5 control subjects (CTRL, 4 men, 1 woman). ET-1 and AM plasma levels in pulmonary artery (mixed venous blood, ven) and aorta or femoral artery (arterial, art), were measured at baseline and during dobutamine infusion (5-10-15 mcg kg(-1) min(-1)). The Ppa/CO coordinates obtained at baseline and during dobutamina infusion for each patients were used to calculate the Slope and Intercept by linear regression analysis. RESULTS: Baseline hemodynamics measurements were similar in the three groups with a trend towards a mild elevation in Ppa in CF group (Ppa mm Hg: CTRL 19+/-3.5, COPD 19.4+/-5.5, CF 22.7+/-7.5). Baseline plasma ET-1(ET-1ven pg ml(-1): CTRL 13.9+/-6.7, COPD 20.1+/-14, CF 20.4+/-7.1; ET-1art pg ml(-1): CTRL 16.7+/-6.4, COPD 20.1+/-11.7, CF 18.1+/-3.9) and AM (AMven pg ml(-1): CTRL 15.8+/-5, COPD 31.8+/-17.6, CF 27.7+/-7.6; AMart pg ml(-1): CTRL 15.9+/-1.4, COPD 21.4+/-3.8, CF 27+/-7.6) showed a trend towards higher value among patients' groups compared to the controls. Baseline ET-1 pulmonary gradient did not show significant difference among the three groups as well AM pulmonary gradient. Dobutamine infusion caused a comparable increase of heart rate and CO in the three groups. Mean pulmonary pressure had a trend towards a greater increase in COPD and CF than in controls, consequently, pulmonary Pap/CO relationship showed a steeper slope in patients' groups (Slope mm Hg L(-1) min(-1): CTRL 0.9+/-0.3, COPD 2.1+/-0.8 p<0.02 vs. CTRL, CF 1.9+/-0.9 p<0.03 vs CTRL). During dobutamine plasma ET-1 and AM showed a great individual variability resulting in no significant difference among groups. ET-1 pulmonary gradient showed a trend towards pulmonary uptake in patients' groups (ET-1art-ven pg min(-1): CTRL 2.7+/-2.9, COPD-6.1+/-7.8, CF -4+/-4.8) while AM pulmonary gradient did not show any particular pattern. During dobutamine ET-1 was significantly correlated to Pap/CO characteristics (Slope and ET-1ven, r=-0.59, p<0.05; Slope and ET-1art-ven, r=-0.60, p<0.05; Intercept and ET-1art-ven, r=0.63, p<0.004), and ET-1art-ven was the only independent variable related to Slope and Intercept. CONCLUSIONS: In patients with moderate pulmonary vascular impairment, ET-1 pulmonary gradient, but not AM pulmonary gradient, is inversely correlated with pulmonary incremental resistance, suggesting a role of ET-1 in the regulation of pulmonary vascular resistance.

Effects of abciximab and preprocedural glycemic control in diabetic patients undergoing elective coronary stenting.

BACKGROUND: In diabetic patients, the combination of abciximab with stenting has been demonstrated to be the standard of care to reduce target vessel revascularization (TVR) and mortality. Moreover, a preprocedural hyperglycemia has been associated with a higher rate of TVR after an elective stent implantation. We sought to evaluate the effects of abciximab and/or preprocedural glycemic control on 30 and 180 days of TVR and on 1-year major adverse cardiac events (MACE-cardiac mortality, TVR, and myocardial infarction) in diabetic patients undergoing elective coronary stenting. METHODS: From January 2002 through May 2003, diabetic patients undergoing elective stenting of de novo coronary artery lesions were randomized to abciximab or placebo infusion. Preprocedural hyperglycemia was defined as fasting plasma glucose >or=126 mg/dL (7.0 mmol/L) immediately before the procedure. RESULTS: A total of 122 consecutive patients with diabetes (62.4 +/- 10.2 years, 80 men) were enrolled in the study. Sixty-nine (56.5%) were randomly assigned to receive abciximab (34 with and 35 without preprocedural hyperglycemia) and 53 (43.5%) to placebo (23 with and 30 without hyperglycemia). Target vessel revascularization was significantly lower in diabetic patients who received abciximab at 30 days (2.9% and 2.8% vs 8.7% and 6.6% in nonabciximab group with or without hyperglycemia, respectively, P < .01) but not at 6 months (31.4% and 26.5% vs 30% and 28.7%, P = NS). Conversely, the cumulative incidence of MACE was significantly higher among diabetic patients with preprocedural hyperglycemia (64.7% and 65.2%) versus diabetic patients with preprocedural glycemic control (37.1% and 40%), treated with or without abciximab, respectively (P < .05). CONCLUSIONS: A preprocedural hyperglycemia is associated with a higher rate of MACE, regardless of the use of abciximab, in diabetic patients undergoing elective coronary stenting.

Impact of Heart Rate on Myocardial Salvage in Timely Reperfused Patients with ST-Segment Elevation Myocardial Infarction: New Insights from Cardiovascular Magnetic Resonance.

BACKGROUND: Previous studies evaluating the progression of the necrotic wave in relation to heart rate were carried out only in animal models of ST-elevated myocardial infarction (STEMI). Aim of the study was to investigate changes of myocardial salvage in relation to different heart rates at hospital admission in timely reperfused patients with STEMI by using cardiovascular magnetic resonance (CMR). METHODS: One hundred-eighty-seven patients with STEMI successfully and timely treated with primary coronary angioplasty underwent CMR five days after hospital admission. According to the heart rate at presentation, patients were subcategorized into 5 quintiles: <55 bpm (group I, n = 44), 55-64 bpm (group II, n = 35), 65-74 bpm (group III, n = 35), 75-84 bpm (group IV, n = 37), ≥85 bpm (group V, n = 36). Area at risk, infarct size, microvascular obstruction (MVO) and myocardium salvaged index (MSI) were assessed by CMR using standard sequences. RESULTS: Lower heart rates at presentation were associated with a bigger amount of myocardial salvage after reperfusion. MSI progressively decreased as the heart rates increased (0.54 group I, 0.46 group II, 0.38 group III, 0.34 group IV, 0.32 group V, p<0.001). Stepwise multivariable analysis showed heart rate, peak troponin and the presence of MVO were independent predictor of myocardial salvage. No changes related to heart rate were observed in relation to area at risk and infarct size. CONCLUSIONS: High heart rates registered before performing coronary angioplasty in timely reperfused patients with STEMI are associated with a reduction in salvaged myocardium. In particular, salvaged myocardium significantly reduced when heart rate at presentation is ≥85 bpm.

Right Intraventricular Dyssynchrony in Idiopathic, Heritable, and Anorexigen-Induced Pulmonary Arterial Hypertension: Clinical Impact and Reversibility.

OBJECTIVES: The aim of this study was to determine the prevalence of right intraventricular dyssynchrony, its determinants and prognostic impact in idiopathic, heritable, and anorexigen-induced pulmonary arterial hypertension. BACKGROUND: Right ventricular dyssynchrony has been described in pulmonary arterial hypertension, but no evidence is available on its prognostic impact and evolution after therapy. METHODS: In 83 consecutive therapy-naïve patients, right ventricular dyssynchrony was evaluated by 2-dimensional speckle-tracking echocardiography calculating the standard deviation of the times to peak-systolic strain for the 4 mid-basal right ventricular segments (RV-SD4). After baseline (World Health Organization [WHO] class, pulmonary hemodynamics, 6-min walk test [6 MWT]), a second assessment was performed after 12 months or when clinical worsening occurred. RESULTS: Patients with right ventricular dyssynchrony (RV-SD4 >18 ms) had advanced WHO class, worse 6 MWT, right ventricular remodeling, and hemodynamic profile compared with patients ≤ 18 ms. Determinants of dyssynchrony included pulmonary vascular resistance, QRS duration, and right ventricular end-diastolic area (r(2) = 0.38; p < 0.000001). At 12 months, 32.5% of patients presented clinical worsening (actuarial rates: 19% at 6 months, 31% at 1 year). Multivariable models for clinical worsening prediction showed that the addition of RV-SD4 to clinical and hemodynamic variables (WHO IV, 6 MWT, and cardiac index) significantly increased the prognostic power of the model (0.74 vs. 0.81; p = 0.005, 95% confidence interval [CI]: 0.02 to 0.11). Receiver operating characteristic analysis identified RV-SD4 ≥ 23 ms as the best cutoff value for clinical worsening prediction (95% negative predictive value). At 12 months, normalization of dyssynchrony was achieved in patients with a large reduction of pulmonary vascular resistance (-42 ± 4%). CONCLUSIONS: Right ventricular dyssynchrony is frequent in pulmonary arterial hypertension, is an independent predictor of clinical worsening, and might regress during effective treatments.

[New devices for the invasive treatment of acute myocardial infarction]. / Nuovi device nel trattamento invasivo dell'infarto miocardico acuto.

Primary angioplasty has been demonstrated to be the best reperfusion therapy in patients with acute myocardial infarction. Anyway, its efficacy is reduced by the distal embolization, above all in the setting of acute myocardial infarction. In the last years, many devices have been designed in order to limit this complication which may lead to a poor prognosis. This review will focus on the different devices of thrombectomy and distal protection, until now available in a cath lab.

Relationship between baseline ET-1 plasma levels and outcome in patients with idiopathic pulmonary hypertension treated with bosentan.

OBJECTIVES: To address if baseline endothelin-1 (ET-1) plasma levels might predict clinical worsening (CW) in patients with idiopathic pulmonary hypertension (IPAH) treated with bosentan. METHODS: Forty-four consecutive patients with IPAH (WHO classes II-III) were included in this study. After an initial assessment (clinical status, pulmonary hemodynamics, samples for adrenomedullin (ADM), ET-1 and brain natriuretic peptide (BNP) plasma levels), patients were treated with bosentan and followed-up for CW. RESULTS: We observed CW in 24 patients. Actuarial rates of freedom from CW were 74% at 1 year, 56% at 2 years, and 43% at 3 years. Patients with CW had a worse WHO functional class (II/III; no-CW 14/6 vs CW 5/19, p=0.002), six-minute walk-test distance (no-CW 439+94 m vs CW 385+82 m, p=0.04), mean pulmonary artery pressure (no-CW 47.4+10.6mm Hg vs CW 56+12.6mm Hg, p=0.02) and pulmonary vascular resistance (PVR no-CW 12.5+4.8 WU vs CW 16.4+6.3 WU, p=0.03) than the no-CW group. Moreover ET-1 (no-CW 14.1+4.2 pg/ml vs CW 21.3+6.3 pg/ml, p=0.0001), ADM (no-CW 14.9+7 pg/ml vs CW 21.5+10.4 pg/ml p=0.002) and BNP (no-CW 82.8+35.3 pg/ml vs CW 115.4+39.6 pg/ml, p=0.007) plasma levels were significantly higher in the CW group than in the no-CW group. The multivariate Cox proportional hazards model identified WHO class III (RR 4.6, 95%CI 14.6-1.45), ET-1 plasma levels (RR 1.1, 95%CI 2.05-1.01) and PVR (RR 1.2, 95%CI 1.3-1.03) as independent risk factors for CW. CONCLUSIONS: These data confirm the high rate of CW in patients with IPAH treated with bosentan and document the impact of the endothelin system on CW of these patients.

Prognostic factors in severe pulmonary hypertension patients who need parenteral prostanoid therapy: the impact of late referral.

BACKGROUND: Oral drugs have made the treatment of pulmonary hypertension (PH) feasible in non-expert centers, which could delay patient access to prostanoid therapy. METHODS: Fifty-seven consecutive patients with precapillary PH received a prostanoid in our center. Data at prostanoid initiation included modality of center referral, medical history, New York Heart Association [NYHA] class, exercise capacity, echocardiographic parameters, and hemodynamics. RESULTS: Overall survival at 1, 2, and 3 years was 85%, 69%, 55%, respectively. Non-survivors had worse NYHA class III/IV (17/12) than survivors (27/1; p < 0.01) and exercise capacity on 6-minute-walk distance (254 ± 114 vs 354 ± 91 meters; p < 0.01). Non-survivors were more frequently referred on oral therapy (83% vs 36%; p < 0.01) and had a higher rate of urgent prostanoid treatment (69% vs 17%; p < 0.0001). Multivariate analysis (hazard ratio [95% confidence interval]) found the independent prognostic factors were urgent prostanoid therapy (2.0 [1.1-3.9]) and NYHA class (3.5 [1.5-8.2]). Survivors had a significant response to prostanoid, improving NYHA class from 2.8 ± 0.4 to 2.3 ± 0.5 (p = 0.002), 6-minute walk distance from 354 ± 91 to 426 ± 82 meters (p = 0.0001), and pulmonary hemodynamics (pulmonary artery pressure from 56 ± 13 to 44 ± 18 mm Hg [p < 0.05]; cardiac index from 2.0 ± 1.2 to 3.1 ± 1.2 liters/min/m(2) [p = 0.002], and pulmonary vascular resistance from 17 ± 10 to 8 ± 6 WU [p = 0.001]). CONCLUSIONS: Referral of patients on oral treatment to a tertiary PH center is delayed and significantly affects prognosis.