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PURPOSE Mechanisms leading to heart failure (HF) symptoms in aortic valve stenosis (AS) are contentious. We examined the impact of secondary mitral regurgitation (MR) on the symptomatic status in patients with AS. METHODS Outpatients performing echocardiography with any degree of AS, without organic mitral valve disease, mitral valve intervention, or aortic insufficiency were enrolled. MR was quantitatively defined through mitral effective regurgitant orifice area (EROA) using the proximal isovelocity surface area method. Patients were divided into two groups (New York Heart Association [NYHA] class I-II vs. NYHA class III-IV). RESULTS Five hundred and eighty-four patients were enrolled (484 NYHA I-II, 100 NYHA III-IV). More symptomatic patients had smaller aortic valve area (AVA), lower left ventricular ejection fraction (LVEF) and stroke volume, higher E/E', and LV global afterload. MR was present in 178 (30%) patients and EROA was

BACKGROUND Preliminary data suggest that pressure-controlled intermittent coronary sinus occlusion (PICSO) might reduce the infarct size (IS) in patients with anterior ST-elevation myocardial infarction (STEMI). However, the applicability of this therapy to patients with inferior STEMI and its exact mechanism of action is uncertain. METHODS AND RESULTS Thirty-six patients (27 anterior and 9 inferior) with STEMI underwent PICSO-assisted-primary percutaneous intervention (PPCI) and were compared with matched controls who underwent standard PCI (n = 72). Median age was 63 (55-70) years and 82% were male. Coronary microvascular status was assessed using thermodilution-derived index of microcirculatory resistance (IMR) and the vasodilatory capacity was assessed using the resistive reserve ratio (RRR). IS and microvascular obstruction (MVO) were assessed using cardiovascular magnetic resonance imaging (CMR) within 48 h and 6 months of follow-up. At completion of PPCI, IMR improved significantly in PICSO-treated patients compared with controls in patients with either anterior (63.7 [49.8-74.6] vs. 35.9 [27.9-47.6], p

Background Leadless pacemaker (LP) therapy has been proved effective in cases where traditional transvenous right pacing (TRP) failed. TRP through a bioprosthetic tricuspid valve (BTV) has always been considered an unpreferable solution because of possible deleterious effect of permanent pacing leads on BTV function and specifically on tricuspid regurgitation (TR). Very limited data exist about the feasibility and safety of LP implantation in this setting. Methods We describe two cases of LP implantation through BTV in patients with failure of epicardial pacemaker implanted after cardiac surgery. The focus is on technical description of the procedure and on electrical and echocardiographic evaluation at implantation and at the follow‐up. Results In both cases, skilled and careful handling of the delivery system as well as proper use of X‐ray oblique views was determinant for atraumatic successful valve crossing. Likewise, an accurate selection of the deployment site inside the right ventricle, far enough from the valve to avoid valvular dysfunction, was important for successful implantation. Electrical parameters of LP were satisfying at implantation and at the follow‐up. The echocardiogram after implantation and at the follow‐up showed no mechanical interference of LP with prosthetic valve, no significant TR, and absence of significant changes in the biventricular function. Conclusion Our data seem to support feasibility and safety of this type of procedure in skilled hands, allowing efficacious pacing without valvular dysfunction or right ventricular (RV) physiology impairment., Leadless pacemaker (LP) therapy has been proved effective in cases where traditional transvenous right pacing (TRP) failed. TRP through a bioprosthetic tricuspid valve (BTV) has always been considered an unpreferable solution because of possible deleterious effect of permanent pacing leads on BTV function and specifically on tricuspid regurgitation (TR). Very limited data exist about the feasibility and safety of LP implantation in this setting. We describe two cases of LP implantation through BTV in patients with failure of epicardial pacemaker implanted after cardiac surgery. The focus is on technical description of the procedure and on electrical and echocardiographic evaluation at implantation and at the follow‐up. In both cases, skilled and careful handling of the delivery system as well as proper use of X‐ray oblique views was determinant for atraumatic successful valve crossing. Likewise, an accurate selection of the deployment site inside the right ventricle, far enough from the valve to avoid valvular dysfunction, was important for successful implantation. Electrical parameters of LP were satisfying at implantation and at the follow‐up. The echocardiogram after implantation and at the follow‐up showed no mechanical interference of LP with prosthetic valve, no significant TR, and absence of significant changes in the biventricular function. Our data seem to support the feasibility and safety of this type of procedure in skilled hands, allowing efficacious pacing without valvular dysfunction or RV physiology impairment.

Hepatitis C virus (HCV)-related chronic infection has been associated with a higher incidence of cardiovascular diseases. An altered morphology and function of both left and right heart have been described in HCV patients; however, the causality of the association is still debated. Ninety-eight nonobese and nondiabetic HCV patients (59.5 ± 12.0 years; males 52%) with Fibroscan-Transient Elastography assessed low-moderate liver fibrosis that achieved sustained viral response at 12 and 24 weeks after DAAs (direct-acting antivirals) participated. 56 were matched with 52 control subjects for age, sex and cardiovascular risk factors at baseline. A trans-thoracic echocardiography was performed in each subject at baseline (T0) and repeated in all HCV patients after eradication (6 months later eligibility, T1). TNF-α and IL-10 were measured at baseline and at T1. A concentric remodelling of the left heart in HCV participants was identified, whereas tricuspidal annular plane systolic excursion, right indexed atrial volume, right basal ventricular diameter, inferior vena cava diameter and pulmonary arterial pressure were higher in HCV participants compared to matched controls. After virus eradication, left indexed atrial volume and all right cardiac chambers measures were lower than baseline. A significant reduction of TNF-α was shown at T1, while IL-10 did not change. This study shows a concentric remodelling of the left ventricle and structural modifications in the right sections in HCV patients compared to controls. Virus eradication with DAAs was associated with a reduction of the main right atrioventricular parameters indicating a direct involvement of the HCV in cardiac changes.

Aims In the randomized GRAFFITI trial, surgeons drew their strategy based on coronary angiography. When patients were randomized to fractional flow reserve (FFR)-guidance, surgeons were informed of the FFR values and asked to redraw their strategy. The aim of this study was to investigate the changes induced by FFR knowledge. Methods and results The intended and performed strategy (before and after FFR) were compared. Among 172 patients, 84 with 300 lesions were randomized to the FFR-guided group. The intended strategy was to bypass 236 stenoses:108 with a venous and 128 with an arterial graft. After disclosing FFR, a change in strategy occurred in 64 lesions (21.3%) of 48 (55%) patients. Among 64 lesions for which the intended strategy was medical therapy, 16 (25%) were bypassed after disclosing FFR. The number of procedures with >1 venous graft planned was significantly reduced from 37 to 27 patients (p = .031). The proportion of on-pump surgery was significantly reduced from 71 to 61 patients (p = .006). The rates of clinical events at 1 year were similar between patients with or without at least one change in strategy. Discussion FFR-guided CABG is associated with a simplified surgical procedure in 55% of the patients, with similar clinical outcomes.

Reemplaçament de la vàlvula aòrtica; Qualitat de vida; Qüestionari Reemplazo de la válvula aórtica; Calidad de vida; Cuestionario Aortic valve replacement; Quality of life; Questionnaire Aims There is no quality of life tool specifically developed for patients with severe aortic stenosis (AS) to assess how this chronic condition and its treatment affect patients. The Toronto Aortic Stenosis Quality of Life Questionnaire (TASQ) has been developed to overcome this gap. The results of the validation of the TASQ in patients undergoing treatment for severe AS are presented. Methods and results Prospective study at 10 centres in Europe and Canada, which enrolled 274 patients with severe symptomatic AS undergoing surgical or transcatheter aortic valve replacement. Mean TASQ score at baseline was 71.2 points and increased to 88.9 three months after aortic valve implantation (P < 0.001). Increases were seen for the emotional impact (32.0 to 39.0; P < 0.001), physical limitations (14.8 to 22.0; P < 0.001), and physical symptoms (8.5 vs. 11.0; P < 0.001) domains. Internal consistency was good/excellent for overall TASQ score (α = 0.891) and for the physical limitation, emotional impact, and social limitation domains (α = 0.815–0.950). Test–retest reliability was excellent or strong for the overall TASQ (intraclass correlation coefficient of 0.883) and for the physical symptoms, physical limitation, emotional impact, and social limitation domains (intraclass correlation coefficient of 0.791–0.895). Responsiveness was medium overall (Cohen's d = 0.637) and medium/large for physical symptoms, emotional impact, and physical limitations (0.661–0.812). Sensitivity to change was significant for physical symptoms, physical limitations (both P < 0.001), emotional impact (P = 0.003), and social limitations (P = 0.038). Conclusions The TASQ is a new, brief, self‐administered, and clinically relevant health‐specific tool to measure changes in quality of life in patients with AS undergoing an intervention. This work was supported by a research grant provided by Edwards Lifesciences (Nyon, Switzerland) to the Institute for Pharmacology and Preventive Medicine (Cloppenburg, Germany).

Hybrid multidisciplinary interventions are attractive care options for heart valve and vascular diseases in high-risk patients. We describe the feasibility of staged hybrid aortic arch repair to treat a type Ia endoleak and transcatheter aortic valve replacement to treat an aortic valve stenosis, achieving an escape strategy to treat an unexpected type-A aortic dissection.

BACKGROUND: Trastuzumab (TZ) therapy requires careful monitoring of left ventricular (LV) ejection fraction (LVEF) because it can be potentially cardiotoxic. However, LVEF is an imperfect parameter and there is a need to find other variables to predict cardiac dysfunction early. Left atrium (LA) enlargement has proven to be a powerful predictor of adverse outcomes in several disease entities. HYPOTHESIS: Baseline LA volume enlargement might predict TZ‐related LV dysfunction. METHODS: HER2‐positive breast cancer patients receiving TZ and undergoing transthoracic echocardiography at baseline and at follow‐up every 3 months were retrospectively recruited. One‐hundred sixty‐two patients formed the study population. RESULTS: Baseline LAVI was dilated in 14 patients (8.6%). Mean follow‐up was 14 ± 4 months. Cardiotoxicity occurred in 24 patients (14.8%). LAVI was an independent predictor of TZ‐induced LV dysfunction in a clinical model, after adjustment for age and hypertension (odds ratio per 5‐mL/m(2) LAVI increase: 1.34, 95% confidence interval: 1.03‐1.82, P = 0.03); and in a hemodynamic model, including ventricular sizes and systolic blood pressure level (odds ratio per 5‐mL/m(2) LAVI increase: 1.34, 95% confidence interval: 1.01‐1.81, P = 0.04). The predicted probability of developing cardiotoxicity increased progressively, in parallel with LAVI values. CONCLUSIONS: Baseline LA dilatation emerges as a condition associated with the development of cardiotoxicity in HER2‐positive breast cancer patients treated with TZ.

Objectives In-stent restenosis (ISR) and diffuse small vessel disease still represent challenging subsets for percutaneous coronary interventions, also in the new-generation DES era. We aim at reporting on the long-term clinical outcome of drug-coated balloons (DCB) in all-comers population. Methods Consecutive patients treated with DCB between January 2011 and December 2014 were retrospectively studied in three centers of northern Italy. The measured end-points were cardiac death, myocardial infarction (MI), target lesion revascularization (TLR), and major adverse cardiac events (MACE) defined as combination of cardiac death, MI, and TLR. Results We included 143 patients. Of the 167 lesions treated, 41 (24.5%) were de novo lesions in small coronary vessels (

Dyspnea and hypoxemia are common postoperative problems after pneumonectomy. One of the rarer causes of respiratory distress after right pneumonectomy is the development of a significant right-to-left shunt across a patent foramen ovale (PFO), which can evolve at a variable interval of time after the operation. We report here our experience with a patient who underwent right pneumonectomy, followed by several complications, and who presented severe dyspnea 7 months later, after the closure of a right thoracostomy. This report outlines the management of this challenging clinical condition; transesophageal echocardiography (TOE) provided a clear diagnosis and guided an effective percutaneous treatment.

Catheter-based treatment of aortic regurgitation (AR) often proves challenging especially due to associated anatomical difficulties. Here, we present a case of CoreValve implantation with a novel use of the valve-in-valve technique to effectively treat severe AR in a patient with repeated cardiac surgery and aneurismatic prosthetic ascending aorta. © 2013 Wiley Periodicals, Inc.

Background and Objective Late and very-late stent occlusion remains a serious complication of coronary stenting. Despite their high anti-restenotic efficacy, drug-eluting stents (DES) have been associated to more late-thrombosis as compared to bare-metal stents (BMS). The aim of this study is to analyze the clinical presentation, angiographic, and intravascular ultrasound (IVUS) findings in patients with late or very late stent thrombosis and the relationship with the antiplatelet regimen. Methods and Results Between January 2007 and December 2011, 34 consecutive patients with clinical syndromes compatible with late or very-late stent occlusion were studied with IVUS during emergency catheterization; 25 had DES and 9 had BMS. Thrombotic total occlusion was more common in DES (16 = 64%) than BMS patients (2 = 22%; P = 0.02) and ST-segment elevation myocardial infarction was the predominant clinical presentation in the former group (60% compared to 22%; P = 0.05). The time elapsed between implantation and failure was much longer in DES patients: 33 ± 22 versus 17 ± 14 months for BMS; P = 0.05. IVUS analysis showed a higher incidence of incomplete stent apposition (ISA) in the DES group compared to the BMS group (56% vs. 11%; P = 0.005) and in-stent plaque rupture was the most common finding in the BMS group (78%). In DES group, ISA was found more frequently in patients still under dual antiplatelet therapy (71%). Conclusions Very late DES failure often causes ST-elevation myocardial infarction; these very late events may not correlate with the interruption of antiplatelet therapy. Severe, late acquired ISA belongs to DES and is frequently observed in patients with very late DES thrombosis. © 2013 Wiley Periodicals, Inc.

Diagnostic delay in patients suffering massive pulmonary embolism (PE) on chronic thromboembolic pulmonary hypertension (CTEPH) has inevitably fatal consequences. Indications to pulmonary thromboendarterectomy (PTE) and extracorporeal membrane oxygenation (ECMO) are limited by severe comorbid conditions, some of which, as neurologic disease, absolutely contraindicate these procedures. We reported the clinical course of a severely diseased patient with a history of meningitis, psychosis and epilepsy, experiencing acute massive pulmonary embolism complicated by acute respiratory failure, successfully treated by ECMO and PTE. A 51-year-old woman with massive PE complicating a misdiagnosed CTEPH needed mechanical ventilation because of acute respiratory insufficiency. Thoracic computed tomography (CT) scan demonstrated PE, and brain CT showed multiple cerebral and cerebellar ischemic lesions. Veno-venous ECMO assistance was instituted despite CT imaging. She recovered from acute respiratory insufficiency by means of veno-venous ECMO. Weaning from ECMO was however impossible until surgical exploration demonstrated an underlying chronic CTEPH, which was successfully addressed by PTE, switching the ECMO system to a standard cardiopulmonary bypass. Postoperative course was uneventful and the patient was discharged home in healthy condition. Despite the fact that the cost-effective ratio should always be considered in advanced life support, expanding the commonly accepted selection criteria for expensive procedures might be advisable in selected acute life-threatening cases, in view of the possibility to unexpectedly save lives.

Background and purpose: Tobacco smoke represents a relevant risk factor for coronary heart disease (CHD). Although peroxisome proliferator-activated receptor (PPAR)γ activation reduces inflammation and atherosclerosis, expression of PPARγ in cells and its modulation by smoking are poorly investigated. We previously reported that monocyte/macrophages from healthy smokers exhibited an enhanced constitutive expression of PPARγ. Here, we evaluated PPARγ expression and basal cytokine release in monocytes and monocyte-derived macrophages (MDMs) from 85 CHD patients, classified by their smoking habit (smokers, non-smokers and ex-smokers), and assessed the role of PPARγ ligands in this context. Experimental approach: PPARγ protein was detected by Western blot and semi-quantified by PPARγ/β-actin ratio; cytokine release was measured by elisa and nuclear factor-kappaB (NF-κB) translocation by electrophoretic mobility shift assays. Key results: As compared to the other groups, MDMs from smoker CHD patients exhibited a reduced PPARγ/β-actin ratio and an increased spontaneous release of tumour necrosis factor-α (TNF-α) and interleukin-6, but with no major variations in monocytes. In cells from selected CHD patients, rosiglitazone inhibited TNF-α release and NF-κB translocation induced by phorbol-12-myristate 13-acetate. The selective PPARγ antagonist GW9662 reversed these effects, with some variations related to smoking habit. Conclusions and implications: In CHD patients, exposure to tobacco smoke profoundly affected PPARγ expression, and this was related to levels of secretion of pro-inflammatory cytokines. MDMs from CHD smokers showed the lowest PPARγ expression and released more inflammatory cytokines. Moreover, rosiglitazone's ability to inhibit cytokine release and its reversal by GW9662 clearly indicated PPARγ involvement in these changes in CHD patients.

Background and purpose: Substance P (SP) and peroxisome proliferator-activated receptor-γ (PPAR-γ) play important roles in different inflammatory conditions and are both expressed in human monocytes and macrophages. However, it is not known whether or not they interact. This study was undertaken to evaluate the effects of SP on PPAR-γ protein expression in monocytes and macrophages (MDMs: monocyte-derived macrophages) from healthy smokers and non-smokers. Experimental approach: PPAR-γ protein was detected by western blot and quantified by calculating the ratio between PPAR-γ and β-actin protein expression. Constitutive tachykinin NK1 receptor expression in monocytes and MDMs from healthy smokers and non-smokers was evaluated by western blot. Cytokine release was evaluated by ELISA. Key results: In the concentration range 10−10–10−6 M, SP stimulated PPAR-γ protein expression in monocytes and MDMs, being more effective in cells from healthy smokers. Moreover, in these cells there was a constitutively increased expression of NK1 receptors. SP-induced expression of the PPAR-γ protein was receptor-mediated, as it was reproduced by the NK1 selective agonist [Sar9Met(O2)11]SP and reversed by the competitive NK1 antagonist GR71251. SP-induced maximal effects were similar to those evoked by 15-deoxy-Δ12,14-prostaglandin J2; an endogenous PPAR-γ agonist, and were significantly reduced by a PPAR-γ antagonist. NK1 and PPAR-γ agonists exerted opposite effects on TNF-α release from monocytes and MDMs. Conclusions and implications: Enhancement of PPAR-γ protein expression represents a novel activity for SP, which could contribute to a range of chronic inflammatory disorders.

Background: Oral treatment with prednisone has demonstrated efficacy in reducing restenosis after percutaneous coronary interventions (PCI). However, administration of steroids at high dose may raise concerns in terms of applicability and tolerability. Monitoring the occurrence of possible side-effects is therefore mandatory. Methods: Secondary effects of oral prednisone in this setting is analyzed. The “expected” secondary effects of the steroid treatment are described, together with the “unexpected” occurrence of likely drug-induced neutropenia observed in patients prescribed prednisone and thienopyridines simultaneously after PCI. Results: Two-hundred and twenty patients were monitored for the occurrence of side-effects of the prednisone therapy. Twenty-eight patients (14%) had side-effects likely related to the prednisone treatment: gastric pain (4%), increment of arterial pressure needing upgrading of antihypertensive treatment (4%), edema (1.8%), and concomitant infections (1.4%). In three patients (1.4%), agranulocytosis was detected at the time of the routine blood cell count scheduled 4 weeks after PCI in otherwise asymptomatic patients. Neutropenia subsided completely after withdrawal of prednisone and thienopyridine in all cases and the blood cell formula normalized within 3 weeks. Conclusions: Side-effects of oral prednisone given after PCI to reduce restenosis occur in less than 15% of patients. Complaints are mild and reversible and can be easily managed with adjunctive diuretic and antacid drugs. The occurrence of agranulocytosis after prednisone had never been reported before, but was observed in 1.4% of our patients receiving simultaneously a thienopyridine. To explain such an unusual event we propose the hypothesis of a possible metabolic interaction between prednisone and thienopyridines.

Aim of the study was to assess the clinical and angiographic efficacy of oral treatment with prednisone at immunosuppressive dosage after percutaneous coronary interventions (PCI) in patients with bifurcation lesions treated with elective bare metal stent (BMS) implantation in the main-branch (MB) and provisional stenting in the side-branch (SB). Twenty-five patients were treated on 29 bifurcation lesions (58 vessel segments). Lesion preparation before stenting was performed with atherectomy in 7 cases, and balloon PCI over double wires in all other cases; none was treated directly with stents. The mean length of stents implanted in the MB was 19.6 +/- 4.9 mm (10-30 mm). Balloon PCI was successful in 23 of 29 SB and provisional stenting was needed in 6 SB (21%). All patients received oral prednisone according to the immunosuppressive protocol previously reported (1 mg/kg/day/10 days, 0.5 mg/kg/day/20 days, 0.25 mg/kg/day/15 days). At 12 months, one patient had recurrence of angina (4%) and two patients underwent repeated target lesion revascularization (8%). No patient died or had stent thrombosis. Quantitative coronary analysis was performed in all patients at 8 months. Global restenosis rate per vessel was 8.6% (5/58), and 17.2% (5/29) per lesion. The restenosis rate and late lumen loss were 3.4% and 0.36 +/- 0.6 mm, and 13.8% and 0.47 +/- 0.46 mm in the MB and the SB, respectively. Single stent implantation in the MB and provisional stenting of the SB is feasible in most cases after adequate lesion preparation. The systemic treatment with oral prednisone after BMS implantation offers good clinical and angiographic results even in the difficult setting of bifurcation lesions.

Regional intra-arterial infusion of human placental lactogen in anaesthetized pigs has been shown to cause coronary, renal and iliac vasoconstriction by antagonizing the vasodilatory effects of beta2-adrenergic receptors. Since nitric oxide is known to modulate or mediate beta2-adrenergic effects, the present study was planned in the same experimental model to determine the role of nitric oxide in the above vascular responses to human placental lactogen. In eight pigs anaesthetized with sodium pentobarbitone, changes in anterior descending coronary, left renal and left internal iliac blood flow caused by intra-arterial infusion of human placental lactogen at constant heart rate and arterial blood pressure were assessed using electromagnetic flowmeters. Intra-arterial infusion of the human placental lactogen caused decreases in coronary, renal and iliac blood flow which, respectively, averaged 16.7, 8.1 and 12.2% of the baseline values. The role of nitric oxide in this response was studied in the same pigs by repeating the experiments, after measured blood flows had returned to baseline values, following intra-arterial administration of N(omega)-nitro-L-arginine methyl ester (L-NAME). The subsequent intra-arterial infusion of human placental lactogen did not cause any significant changes in measured blood flows, even when performed after reversing the increase in arterial blood pressure and coronary, renal and iliac resistance caused by L-NAME with continuous intravenous infusion of papaverine. These results indicate that the coronary, renal and iliac vasoconstriction caused by human placental lactogen, known to involve antagonism of beta2-adrenergic vasodilatory effects, was mediated by inhibition of nitric oxide release.

Severe coronary artery disease often coexists with peripheral vascular atherosclerosis. The assessment of the supra-aortic circulation in candidates for surgical coronary revascularization is of clinical relevance, and after intervention the patency of the supra-aortic trunks should be regularly evaluated in the clinical follow-up. We describe three cases of coronary artery disease treated with surgical revascularization using the internal mammary artery and concomitant atherosclerotic disease of the subclavian artery. The clinical presentation, the diagnostic procedures, and the therapeutic approach by means of percutaneous transluminal angioplasty of the subclavian artery are described and discussed.