Search

Background Non-painful diagnostic procedures require an inactive state for a prolonged time, so that sedation is often needed in younger children to perform the procedures. Our standard of care in this setting consists of the association between oral midazolam (0.5 mg/kg) and intranasal dexmedetomidine (4 mcg/kg). One of the limits of this approach is that the onset of action is quite delayed (up to 55 min) and poorly predictable. We chose to compare this association with intranasal-ketamine and intranasal-dexmedetomidine. Methods This is a “pre-post” study. The study population included the first forty children receiving sedation with the “new” combination intranasal ketamine (3 mg/kg) and intranasal dexmedetomidine (4 mcg/kg) compared to a historical cohort including the last forty children receiving sedation with our standard of care combination of intranasal dexmedetomidine (4mcg/kg) and oral midazolam (0,5 mg/kg). Results The association intranasal dexmedetomidine and intranasal ketamine allowed for a significantly shorter sedation induction time than the combination intranasal dexmedetomidine and oral midazolam (13,5 min versus 35 min). Both group’s cumulative data showed a correlation between age and sedation effectiveness, with younger children presenting a higher success rate and shorter induction time (p 0,001). Conclusions: This study suggests that the ketamine and dexmedetomidine intranasal association may have a shorter onset of action when compared to intranasal dexmedetomidine and oral midazolam.

Background Current guidelines suggest to consider dual antiplatelet therapy (DAPT) continuation for longer than 12 months in selected patients with myocardial infarction (MI). Hypothesis We sought to assess the criteria used by cardiologists in daily practice to select patients with a history of MI eligible for DAPT continuation beyond 1 year. Methods We analyzed data from the EYESHOT Post-MI, a prospective, observational, nationwide study aimed to evaluate the management of patients presenting to cardiologists 1 to 3 years from the last MI event. Results Out of the 1633 post-MI patients enrolled in the study between March and December 2017, 557 (34.1%) were on DAPT at the time of enrolment, and 450 (27.6%) were prescribed DAPT after cardiologist assessment. At multivariate analyses, a percutaneous coronary intervention (PCI) with multiple stents and the presence of peripheral artery disease (PAD) resulted as independent predictors of DAPT continuation, while atrial fibrillation was the only independent predictor of DAPT interruption for patients both at the second and the third year from MI at enrolment and the time of discharge/end of the visit. Conclusions Risk scores recommended by current guidelines for guiding decisions on DAPT duration are underused and misused in clinical practice. A PCI with multiple stents and a history of PAD resulted as the clinical variables more frequently associated with DAPT continuation beyond 1 year from the index MI.

Aim: Primary objectives of the study were to assess the safety of transarterial chemoembolization (TACE) using DC Bead LUMI™ for the treatment of hepatocellular carcinoma and beads distribution after TACE. Patients/methods: This was a prospective observational cohort study. The study included 44 hepatocellular carcinoma patients who were treated with TACE using DC Bead LUMI. Beads distribution was monitored 1 h after TACE by CT scan. Results: TACE had no intraprocedural complications. Observed side effects were of mild intensity and included pain in 5 (11%), fever in 4 (9%) and vomiting in 2 (5%) patients. Most patients (89%) reported no adverse event. Non-target distribution was observed in only two cases (5%). Conclusion: DC Bead LUMI allowed assessing in real time their distribution. This could prevent non-target infusion and reduce toxicity.

Aims Patients with acute coronary syndromes (ACSs) who are managed without coronary revascularization represent a mixed and understudied population that seems to receive suboptimal pharmacological treatment. Methods and results We assessed patterns of antithrombotic therapies employed during the hospitalization and in-hospital clinical events of medically managed patients with ACS enrolled in the prospective, multicentre, nationwide EYESHOT (EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units) registry. Among the 2585 consecutive ACS patients enrolled in EYESHOT, 783 (30.3%) did not receive any revascularization during hospital admission. Of these, 478 (61.0%) underwent coronary angiography (CA), whereas 305 (39.0%) did not. The median GRACE and CRUSADE risk scores were significantly higher among patients who did not undergo CA compared with those who did (180 vs. 145, P < 0.0001 and 50 vs. 33, P < 0.0001, respectively). Antithrombotic therapies employed during hospitalization significantly differ between patients who received CA and those who did not with unfractioned heparin and novel P2Y12 inhibitors more frequently used in the first group, and low-molecular-weight heparins and clopidogrel in the latter group. During the index hospitalization, patients who did not receive CA presented a higher incidence of ischaemic cerebrovascular events and of mortality compared with those who underwent CA (1.6 vs. 0.2%, P = 0.04 and 7.9 vs. 2.7%, P = 0.0009, respectively). Conclusion Almost one-third of ACS patients are managed without revascularization during the index hospitalization. In this population, a lower use of recommended antiplatelet therapy and worse clinical outcome were observed in those who did not undergo CA when compared with those who did. Clinical Trial Registration Unique identifier: [NCT02015624][1], . [10.1093/ehjcvp/pvv017][2] [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT02015624&atom=%2Fehjcardpharm%2F1%2F3%2F168.atom [2]: /lookup/doi/10.1093/ehjcvp/pvv017

Aims In the last decades, several new therapies have emerged for the treatment of acute coronary syndromes (ACS). We sought to describe real-world patterns of use of antithrombotic treatments in the catheterization laboratory for ACS patients undergoing percutaneous coronary interventions (PCI). Methods EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalized in iTalian cardiac care units was a nationwide, prospective registry aimed to evaluate antithrombotic strategies employed in ACS patients in Italy. Results Over a 3-week period, a total of 2585 consecutive ACS patients have been enrolled in 203 cardiac care units across Italy. Among these patients, 1755 underwent PCI (923 with ST-elevation myocardial infarction and 832 with non-ST-elevation ACS). In the catheterization laboratory, unfractioned heparin was the most used antithrombotic drug in both ST-elevation myocardial infarction (64.7%) and non-ST-elevation ACS (77.5%) undergoing PCI and, as aspirin, bivalirudin and glycoprotein IIb/IIIa inhibitors (GPIs) more frequently employed before or during PCI compared with the postprocedural period. Any crossover of heparin therapy occurred in 36.0% of cases, whereas switching from one P2Y12 inhibitor to another occurred in 3.7% of patients. Multivariable analysis yielded several independent predictors of GPIs and of bivalirudin use in the catheterization laboratory, mainly related to clinical presentation, PCI complexity and presence of complications during the procedure. Conclusion In our contemporary, nationwide, all-comers cohort of ACS patients undergoing PCI, antithrombotic therapies were commonly initiated before the catheterization laboratory. In the periprocedural period, the most frequently employed drugs were unfractioned heparin, leading to a high rate of crossover, followed by GPIs and bivalirudin, mainly used during complex PCI. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02015624.

Aim To report clinical outcomes of transarterial chemoembolization (TACE) using drug-eluting beads (DEBs) loaded with doxorubicin for the treatment of unresectable intrahepatic cholangiocarcinoma (CCA). Patients and methods We treated 127 patients with doxorubicin via TACE. Inclusion criteria were: diagnosis of unresectable CCA; indication for TACE, performance status (PS) 0-2, >3 months of life expectancy, >18 years old, written consent. TACE was performed using DEBs for 109 (86%) patients and polythylene glycol drug-elutable microspheres (PEG) loaded with doxorubicin for 18 (14%) patients. Results Tumor response of the whole sample of 127 patients was partial response (PR) in 19 (15%) patients, stable disease (SD) in 101 (80%) and progressive disease (PD) in seven (5%) 3 months after therapy, with no complete responses. There were differences between type of embolics: PR was 7% and 77%, SD was 88% and 8%, and PD was 5% and 15%, and the disease control rate was 95% and 85% in the DEB and PEG groups, respectively. Most frequent side-effects were: abdominal pain, fever, nausea, and transaminase rise. Conclusion TACE was effective and safe for CCA treatment, with a high disease control rate. The best response of PEG-TACE was PR, whereas it was SD for DEB-TACE.

Aim of the study is to assess the reliability and correlation with surgical peritoneal cancer index (PCI) of combined PET/CT and ceCT scans (PET/ceCT) performed in a session in patients with peritoneal carcinomatosis candidates for cytoreductive surgery (CS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We retrospectively analyzed data collected from 27 patients with different types of peritoneal carcinomatosis candidates to CS + HIPEC who underwent FDG PET/ceCT in a single session. Two nuclear medicine physicians and two radiologists independently and blindly evaluated PET/CT and ceCT imaging, respectively. In the case of discordance, the consensus was reached by a discussion between the specialists. Moreover, the combined images were evaluated by all the specialists in consensus. The PCIs obtained from surgical look, PET/CT, ceCT, and PET/ceCT were compared with each other. The coefficients of correlation (r) were calculated. The study was conducted after approval of local ethics committee. Surgical PCI was available in 21 patients. The coefficient of correlation between PCI of PET/CT and surgery was 0.528, while it resulted higher between PET/ceCT and surgery (r = 0.878), very similar to ceCT and surgery (r = 0.876). The r coefficient between surgical PCI and PET/CT was higher in patients with a non-mucinous cancer (n = 12) than the counterpart (0.601 vs. 0.303) and the addition of ceCT significantly increases the correlation (r = 0.863), which is anyway similar to ceCT alone (r = 0.856). PET/ceCT as single examination is more accurate than PET/CT but not than ceCT alone for the definition of PCI in a selected group of patients candidates to CS + HIPEC.

Although transcatheter aortic valve implantation (TAVI) for severe aortic stenosis is becoming an established technique, the effect of gender-related differences is poorly described. We performed a gender-based comparison of high-risk patients undergoing TAVI with the self-expandable CoreValve Revalving System for severe aortic stenosis to evaluate early and mid-term clinical outcomes. From the Italian prospective CoreValve registry, 659 consecutive patients (55.8% women) who underwent TAVI were included in the present study. We analyzed the gender-based differences in terms of clinical, angiographic, and procedural features and the differences in the rate of early and mid-term major adverse cardiac and cerebrovascular events. The men were younger, presented more often with severe left ventricular dysfunction, and had a greater rate of previous myocardial infarction, coronary revascularization, peripheral artery disease, renal failure, and heart conduction disorders than the women. The logistic European System for Cardiac Operative Risk Evaluation score did not differ between the 2 groups. The overall unadjusted and adjusted analyses failed to show significant differences between genders in terms of major adverse cardiac and cerebrovascular events at a median follow-up of 13 months (range 8 to 18). At late follow-up (landmark analysis >12 months), a survival benefit was observed in women (hazard ratio 0.27, 95% confidence interval 0.09 to 0.84, p = 0.02). In conclusion, in this multicenter registry, the gender-based comparison of TAVI patients showed that men, despite the younger age, had more extensive atherosclerotic burden compared to women. Overall, the early and mid-term outcomes were similar between genders, although women might have a survival benefit with longer follow-up.

The paucity of evidences about the long-term durability of currently available transcatheter prostheses is one of the main issues of transcatheter aortic valve implantation (TAVI). We sought to assess 3-year clinical and echocardiographic outcomes of patients undergoing TAVI with the third generation CoreValve prosthesis (Medtronic Incorporation, MN, USA).From the Italian CoreValve registry, 181 who underwent TAVI from June 2007 to August 2008 and eligible for 3-year follow-up were analysed. All outcomes were defined according to the Valve Academic Research Consortium. All-cause mortality at 1, 2, and 3 years was 23.6, 30.3, and 34.8%, respectively. Cardiovascular death at 1, 2, and 3 years was 11.2, 12.1, and 13.5%, respectively. The actuarial survival free from a composite of death, major stroke, myocardial infarction, and life-threatening bleeding was 69.6% at 1 year, 63.5% at 2 years, and 59.7% at 3 years. Patients with renal insufficiency had a higher mortality at 3-year follow-up (49.0 vs. 29.2%, P = 0.007); moreover, patients experiencing post-procedural major or life-threatening bleeding had a higher rate of mortality already seen at 30 days (21.6 vs. 2.8%; P0.001) and this result was sustained at 3-year follow-up (62.2 vs. 27.7%; P0.001). Mean pressure gradients decreased from 52.2 ± 18.1 mmHg (pre-TAVI) to 10.3 ± 3.1 mmHg (1-year post-TAVI) (P0.001); aortic valve area increased from 0.6 ± 0.2 cm(2) (pre-TAVI) to 1.8 ± 0.4 cm(2) (1-year post-TAVI); these results remained stable over the 3 years of follow-up. Paravalvular leak was observed in the majority of patients. There were no cases of progression to moderate or severe regurgitation. No cases of structural valve deterioration were observed.This multicentre study demonstrates that TAVI with the 18-Fr CoreValve ReValving System is associated with sustained clinical and functional cardiovascular benefits in high-risk patients with symptomatic aortic stenosis up to 3-year follow-up. Non-cardiac causes accounted for the majority of deaths at follow-up.

Background— Transcatheter aortic valve implantation (TAVI) is a new option for patients with severe aortic stenosis at high surgical risk. The standard retrograde approach through the femoral artery is contraindicated in case of unfavorable iliofemoral anatomy or extensive disease. In these patients, a trans-subclavian approach may be feasible. Methods and Results— Between June 2007 and July 2009, TAVI with the CoreValve bioprosthesis (Medtronic, Minneapolis, Minn) was performed in 514 consecutive patients at 13 Italian hospitals, using the subclavian approach in 54 cases. The median logistic EuroSCORE was significantly higher in the subclavian (19.4; interquartile range, 12.5 to 29.8) versus femoral group (25.3; interquartile range, 15.1 to 36.6) ( P =0.03), as well as the rate of comorbidities. Procedural success was obtained in 100% versus 98.4% of the subclavian versus femoral groups, respectively ( P =0.62), with intraprocedural mortality of 0% versus 0.9% ( P =1.00). The most common in-hospital complications were a new left bundle-branch block (22.4%) and the need for pacemaker (16.3%). No specific complications for the subclavian access (vessel rupture, vertebral or internal mammary ischemia) were reported. The learning curve for the subclavian approach led to a wider use of local anesthesia. Thirty-day mortality was 0% versus 6.1% in the subclavian versus femoral groups, respectively ( P =0.13). Six-month mortality rate was 9.4% versus 15.8% ( P =0.44), whereas valve-related adverse events were 13.6% versus 13.9% ( P =0.79). Conclusions— TAVI through the subclavian approach appeared feasible and safe, with excellent procedural success and low in-hospital complication rates. This new technique allows patients with contraindications to the femoral approach to be treated with TAVI.

This study aims to verify the reliability of diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) measurements to differentiate benign from atypical/malignant meningiomas and among different sub-types.Pre-operative DWI of 102 patients (74 females, mean age 58 years, age range 34-85 years) affected by a pathologically proven intracranial meningioma were retrospectively reviewed. DWI signal intensity of tumors was classified as hypo-, iso- or hyper-intense to grey matter. ADC values and normalised ADC(ratio) (ADC(meningioma)/ADC(normal appearing white matter)) of the neoplastic tissue (avoiding calcifications and cystic or necrotic areas) were measured by two neuroradiologists unaware of each others' reading. MRI and histological findings were compared.Meningiomas were histologically graded as malignant (1%), atypical (21.5%) and benign (77.5%). Meningothelial, transitional and fibrous were the most frequent benign sub-types (44, 16 and 10 cases, respectively). There was no statistical difference between typical and atypical/malignant meningiomas when considering mean ADC values (0.964 +/- 0.192 x 10(-3) vs 0.923 +/- 0.085 x 10(-3) cm(2)/s, p = 0.3 t-Student) or ADC(ratio) (1.266 +/- 0.290 vs 1.185 +/- 0.115, p = 0.2 t-Student). ADC values or ADC(ratio) did not differ significantly among meningioma sub-types although a nearly significant difference was found between meningothelial and transitional (post hoc analysis p = 0.06). Inter-observer agreement of ADC and ADC(ratio) measurements was high (r = 0.95 and 0.92, respectively, Pearson's linear coefficient). DWI intensity did not reach a significant correlation with meningioma's grading (p = 0.08).According to our study, DWI and ADC measurement do not seem reliable in grading meningiomas or identifying histological sub-types. Hence, these parameters should not be recommended for surgical or treatment planning.

In this study we investigated the impact of acute coronary syndromes (ACSs) on clinical outcomes in patients with unprotected left main coronary artery (ULMCA) stenosis treated with drug-eluting stents (DESs). In this multicenter, retrospective, observational study we enrolled 1,101 patients with ULMCA stenosis treated with DESs. Six hundred eleven patients presented with ACS and 490 had stable coronary artery disease. ACS was defined as the presence of unstable angina or non-ST-segment elevation myocardial infarction (MI). During 2-year follow-up, the adjusted hazard ratio of cardiac mortality and MI of patients with ACS versus stable patients was 2.42 (95% confidence interval 1.37 to 4.28, p = 0.002). We observed a stepwise risk increase, namely patients with stable coronary disease had the lowest risk, patients with unstable angina an intermediate risk, and patients with non-ST-segment elevation MI the highest risk. The increased risk of cardiac mortality and MI of patients with ACS was concentrated in the first year after DES implantation. In conclusion, patients with ULMCA stenosis and ACS treated with DESs have an increased risk of cardiac mortality and MI during the first year after the intervention compared to stable patients.

Determination of coronary flow reserve (CFR) is increasingly being used in cardiac allograft vasculopathy (CAV). We aimed to identify determinants of CFR in heart transplantation (HT).CFR was measured by transthoracic echocardiography in 119 HT recipients (97 men, 22 women; 50 +/- 12 years of age at HT and 8 +/- 5 years post-HT). CFR was expressed as the ratio of hyperemic (adenosine infusion at a rate of 0.14 mg/kg) to basal diastolic flow velocity. Rejection scores (RS) on endomyocardial biopsy were calculated. Angiographic CAV was analyzed using a qualitative grading system. The coronary tree was divided into 17 traits and a CAV severity/diffusion index (SDI) was calculated for each patient, summing the scores assigned to all lesions.Upon multivariate analysis, CFR was related to CAV (p = 0.001), interventricular septum thickness (p = 0.01), ischemic heart disease pre-HT (p = 0.02) and SDI and SDI/segment number (p0.0001 and p = 0.003, respectively). In patients without CAV, CFR was related only to RS for severe grades (p = 0.01).Left ventricular hypertrophy, CAV and its severity/diffusion independently contribute to reduced CFR. In patients without angiographic CAV, CFR was only independently related to RS. Because a high rejection burden is associated with increased risk of CAV, CFR reduction may be an early marker of CAV. Microvascular dysfunction may contribute to the late morbidity and mortality seen in HT.

Objectives The aim of this study was to investigate whether there is a temporal pattern of ischemic events in relation to dual antiplatelet therapy in patients with unprotected left main coronary artery (ULMCA) stenosis treated with percutaneous coronary intervention (PCI). Background Identifying which periods during follow-up of patients with ULMCA stenosis treated with PCI are associated with higher risk of clinical events might help to improve therapeutic strategies. Methods We analyzed data from 15 centers involved in an observational study conducted by the Italian Society of Invasive Cardiology on patients with ULMCA stenosis treated with PCI. Eight hundred ninety-four patients were enrolled. Results At 30-day follow-up, the rate of cardiac mortality and myocardial infarction (MI) was 5.4%. In patients still taking dual antiplatelet therapy, the adjusted incidence rate ratio/10,000 patient-days of the combination of cardiac mortality and MI in the 31- to 180-day interval compared with the 181- to 360-day interval after PCI was 3.64 (p = 0.035). This risk was particularly high in patients with acute coronary syndromes. After stopping clopidogrel, the adjusted incidence rate ratio of cardiac mortality and MI in the 0- to 90-day interval compared with the 91- to 180-day interval was 4.20 (p = 0.009). Conclusions In patients with ULMCA stenosis taking dual antiplatelet therapy there is an increased hazard of cardiac mortality and MI between 31 and 180 days compared with 181 to 360 days. Furthermore, there is an increased hazard of cardiac mortality and MI in the first 90 days after stopping clopidogrel.

AIMS: To describe the procedural performance and 30-day outcomes following implantation using the 18 Fr CoreValve Revalving System (CRS) as part of the multicentre, expanded evaluation registry, 1-year after obtaining CE mark approval. METHODS AND RESULTS: Patients with symptomatic severe aortic stenosis and logistic Euroscore > or =15%, or age > or =75 years, or age > or =65 years associated with pre-defined risk factors, and for whom a physician proctor and a clinical specialist were in attendance during the implantation and who collected the clinical data, were included. From April 2007, to April 2008, 646 patients with a mean age of 81 +/- 6.6 years, mean aortic valve area 0.6 +/- 0.2 cm2, and logistic EuroSCORE of 23.1 +/- 13.8% were recruited. After valve implantation, the mean transaortic valve gradient decreased from 49.4 +/- 13.9 to 3 +/- 2 mmHg. All patients had paravalvular aortic regurgitation < or = grade 2. The rate of procedural success was 97%. The procedural mortality rate was 1.5%. At 30 days, the all-cause mortality rate (i.e, including procedural) was 8% and the combined rate of death, stroke and myocardial infarction was 9.3%. CONCLUSIONS: The results of this study demonstrate the high rate of procedural success and a low 30-day mortality in a large cohort of high-risk patients undergoing transcatheter aortic valve implantation (TAVI) with the CRS.

BACKGROUND Cardiac allograft vasculopathy (CAV) is the major cause of graft failure and death in cardiac transplant recipients after transplantation. We aimed to evaluate the clinical and angiographic outcomes of patients with evidence of CAV who were treated percutaneously with drug-eluting stents (DES-PCI). METHODS Between December 2002 and September 2005, we reviewed the baseline procedural characteristics and the clinical outcome of consecutive cardiac transplanted recipients with evidence of CAV treated with DES-PCI, eligible for at least 9 months of follow-up. RESULTS Fifteen consecutive patients received a total of 18 coronary DESs. Total treated lesions were 20; 12 (60%) involved the left anterior descending artery. CAV was focal in nine patients, diffuse in five patients, and mixed in only one patient. Mean time interval from transplantation to DES implantation was 126 +/- 44 months. Angiographic and procedural success was 100%. There were no adverse in-hospital events. During follow-up (17.9 +/- 8.4 months), two patients died of noncardiac cause. Six patients required a new percutaneous intervention for a repeat revascularization rate of 40%: one patient underwent target lesion revascularization because of in-DES restenosis, one patient had target vessel revascularization because of a new coronary lesion proximal to the stent. Finally, four more patients underwent repeat DES-PCI in a coronary vessel other than the treated one. CONCLUSIONS Although DES implantation seems to be associated with a high procedural success rate and a low restenosis rate, the repeat revascularization rate due to CAV progression remains in nearly half of our study patients.

ObjectivesWe tested whether 3-dimensional electroanatomical voltage mapping (EVM) may help in the differential diagnosis between idiopathic right ventricular outflow tract (RVOT) tachycardia and arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D).BackgroundRight ventricular EVM has been demonstrated to reliably identify low-voltage regions (“electroanatomical scar”), which in patients with ARVC/D correspond to areas of fibrofatty myocardial replacement.MethodsThe study population comprised 27 patients (15 men and 12 women, age 33.9 ± 8 years) with RVOT tachycardia and no echocardiographic/angiographic evidence of right ventricular (RV) dilation/dysfunction, who underwent EVM and endomyocardial biopsy (EMB) for characterization of ventricular tachycardia (VT) substrate before catheter ablation.ResultsElectroanatomical voltage mapping was normal in 20 of 27 patients (74%, group A), with electrogram voltage >1.5 mV throughout the RV. The other 7 patients (26%, group B) showed ≥1 (1.4 ± 07) RV electroanatomical scar area(s) (bipolar voltage

Infarct size has been considered an established marker of left ventricular (LV) remodeling. We assessed the predictive value of myocardial/microvascular injury assessed by delayed enhanced magnetic resonance imaging (MRI) on LV remodeling and LV ejection fraction after primary coronary intervention (PCI) compared with peak troponin levels, an established index of myocardial infarct size. We performed MRI in 76 patients with first acute myocardial infarction 6 +/- 2 days after successful PCI. Necrosis was judged as transmural when delayed enhancement was extended to >or=75% of LV segment thickness. Severe microvascular obstruction was identified as areas of late hypoenhancement surrounded by delayed enhancement. Infarct size was expressed as an index by dividing the total percentage of delayed enhancement involvement by the number of LV segments. LV end-diastolic volume index and function were quantified by 2-dimensional echocardiography at 6 +/- 1 months after acute myocardial infarction. Remodeling was evaluated as a change in LV end-diastolic volume index at follow-up compared with baseline. At univariate analyses, transmural necrosis, severe microvascular obstruction, infarct size, and troponin level were correlated directly with remodeling and inversely with LV function at follow-up (p

Aims The ultrastructural features of the myocardium in arrhythmogenic right ventricular cardiomyopathy (ARVC) have not been systematically investigated so far. The recent discovery of gene mutations encoding intercalated disc proteins prompted us to perform a transmission electron microscopy study on endomyocardial biopsies. Methods and results Twenty-one ARVC probands who fulfilled the international Task Force diagnostic criteria underwent right ventricular endomyocardial biopsy and screening of desmosome (D) protein encoding genes. Myocyte intercalated discs were analysed by transmission electron microscope and the data were compared with those of 10 controls and 10 patients with idiopathic dilated cardiomyopathy. Extensive fibro-fatty replacement with a residual myocardium of 59+ 23% was found in ARVC biopsy samples. Pathogenic D gene mutations were identified in 10 (48%): desmoglein-2 in four, desmoplakin in three and plakophilin-2 in three. Mean D length and D percent length of intercalated disc were significantly higher, D number was significantly lower and D gap was widened in ARVC. Moreover, abnormally located D in 75%, abnormal small junctions in 52%, and pale internal plaques in 32% of ARVC patients were found in the presence of a normal intercalated disc convolution index. Conclusion The ultrastructural evidence of intercalated discs remodelling in ARVC, together with the positive screening of D protein encoding genes in half of probands, are in keeping with an intercellular junction cardiomyopathy.

The outcome of moderate-to-severe ischemic mitral regurgitation with multivessel coronary artery disease is still debated. We analysed the effect of different treatments, i.e. medical therapy (MT), coronary artery by-pass grafting (CABG) alone and CABG with mitral valve surgery (MVS), on the survival and rehospitalization of these patients.Between 1990 and 2002, we identified 111 consecutive patients, aged 73+/-8 years, with chronic moderate-to-severe mitral regurgitation and multivessel coronary artery disease at cardiac catheterization, in absence of primary valve disease. Twenty-two patients were treated by MT, 50 by CABG and 39 by CABG+MVS. Overall, the median clinical and echocardiographic follow-ups were 34.9 and 14.6 months, respectively.Groups differed significantly (p0.03) for left ventricular end-diastolic volume index (MT 153+/-54, CABG 125+/-35, CABG + MVS 129+/-38, ml/m2), ejection fraction (MT 35+/-14, CABG 38+/-13, CABG + MVS 50+/-14, %) and mammary artery graft use (CABG 60, CABG + MVS 74, %). While in-hospital mortality was higher in surgical patients (MT 13.6, CABG 18, CABG + MVS 17.9, %, p=0.09), 7-years mortality showed a trend in favour of CABG + MVS compared to other groups (MT 100, CABG 57, CABG + MVS 29, %, p = 0.1). After adjusting for baseline differences, CABG alone or with MVS had a 57% (HR 0.43, p = 0.005) and 53% (HR 0.47, p = 0.02) risk reduction of combined cardiac death and rehospitalization rate compared to MT. However, only CABG + MVS independently predicted mortality (risk reduction 65%, HR 0.35, p = 0.027).In moderate-to-severe ischemic mitral regurgitation and multivessel coronary artery disease, surgery reduced total cardiac events but only a concomitant MVS significantly improved survival.

Background— Three-dimensional electroanatomic voltage mapping offers the potential to identify low-voltage areas that correspond to regions of right ventricular (RV) myocardial loss and fibrofatty replacement in patients with arrhythmogenic RV cardiomyopathy/dysplasia (ARVC/D). Methods and Results— Thirty-one consecutive patients (22 men and 9 women; mean age, 30.8±7 years) who fulfilled the criteria of the Task Force of the European Society of Cardiology and International Society and Federation of Cardiology (ESC/ISFC) for ARVC/D diagnosis after noninvasive clinical evaluation underwent further invasive study including RV electroanatomic voltage mapping and endomyocardial biopsy (EMB) to validate the diagnosis. Multiple RV endocardial, bipolar electrograms (175±23) were sampled during sinus rhythm. Twenty patients (group A; 65%) had an abnormal RV electroanatomic voltage mapping showing ≥1 area (mean 2.25±0.7) with low-voltage values (bipolar electrogram amplitude 1.5 mV). Low-voltage electrograms appeared fractionated with significantly prolonged duration and delayed activation. In 11 patients (group B; 35%), electroanatomic voltage mapping was normal, with preserved electrogram voltage (4.4±0.7 mV) and duration (37.2±0.9 ms) throughout the RV. Low-voltage areas in patients from group A corresponded to echocardiographic/angiographic RV wall motion abnormalities and were significantly associated with myocyte loss and fibrofatty replacement at EMB ( P P P P =0.02). Conclusions— Three-dimensional electroanatomic voltage mapping enhanced accuracy for diagnosing ARVC/D (1) by demonstrating low-voltage areas that were associated with fibrofatty myocardial replacement and (2) by identifying a subset of patients who fulfilled ESC/ISFC Task Force diagnostic criteria but showed a preserved electrogram voltage, an inflammatory cardiomyopathy mimicking ARVC/D, and a better arrhythmic outcome.

It is unclear whether revascularization of renal artery stenosis (RAS) by means of percutaneous renal angioplasty and stenting (PTRAS) is advantageous over optimal medical therapy. Hence, we designed a randomized clinical trial based on an optimized patient selection strategy and hard experimental endpoints. Primary objective of this study is to determine whether PTRAS is superior or equivalent to optimal medical treatment for preserving glomerular filtration rate (GFR) in the ischemic kidney as assessed by 99mTcDTPA sequential renal scintiscan. Secondary objectives of this study are to establish whether the two treatments are equivalent in lowering blood pressure, preserving overall renal function and regressing target organ damage, preventing cardiovascular events and improving quality of life. The study is designed as a prospective multicentre randomized, un-blinded two-arm study. Eligible patients will have clinical and angio-CT evidence of RAS. Inclusion criteria is RAS affecting the main renal artery or its major branches either >70% or, if

We studied 361 patients, to evaluate risk factors for cardiac allograft vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT). Rejection scores (RS) on endomyocardial biopsy were calculated (first year and whole follow-up). CAV onset was defined as any lesion seen at yearly angiography. A CAV severity/diffusion index was calculated for each patient summing up the scores of all lesions. Cox multivariate analysis included: donor age, sex, and weight; recipient sex, age, pre-HT diagnosis, hypertension, diabetes and hyperlipidemia post-HT; number of treated rejections and RS; and immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year, 22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p0.0001, relative risk (RR) = 9.9], male donor (p0.001, RR = 3.2), high RS for severe (or = 3A) grades (p0.02, RR = 2.01), high cyclosporine at 3 months (p0.02, RR = 1.9). Risk factors for CAV severity/diffusion were higher donor weight (p0.01, RR = 7.5), high prednisone dosage at 1 year (p0.0001, RR = 21.1), and coronary disease pre-HT (p0.002, RR = 9.7). High RS was an independent predictor for CAV onset, not severity/diffusion. This suggests an immune basis for CAV onset and nonimmune modulation for progression. High RS for severe grades may provide a predictor for patients at risk.

background Chronic thromboembolic pulmonary hypertension (CTPH) is associated with considerable morbidity and mortality. Its incidence after pulmonary embolism and associated risk factors are not well documented. methods We conducted a prospective, long-term, follow-up study to assess the incidence of symptomatic CTPH in consecutive patients with an acute episode of pulmonary embolism but without prior venous thromboembolism. Patients with unexplained persistent dyspnea during follow-up underwent transthoracic echocardiography and, if supportive findings were present, ventilation–perfusion lung scanning and pulmonary angiography. CTPH was considered to be present if systolic and mean pulmonary-artery pressures exceeded 40 mm Hg and 25 mm Hg, respectively; pulmonary-capillary wedge pressure was normal; and there was angiographic evidence of disease. results The cumulative incidence of symptomatic CTPH was 1.0 percent (95 percent confidence interval, 0.0 to 2.4) at six months, 3.1 percent (95 percent confidence interval, 0.7 to 5.5) at one year, and 3.8 percent (95 percent confidence interval, 1.1 to 6.5) at two years. No cases occurred after two years among the patients with more than two years of follow-up data. The following increased the risk of CTPH: a previous pulmonary embolism (odds ratio, 19.0), younger age (odds ratio, 1.79 per decade), a larger perfusion defect (odds ratio, 2.22 per decile decrement in perfusion), and idiopathic pulmonary embolism at presentation (odds ratio, 5.70). conclusions CTPH is a relatively common, serious complication of pulmonary embolism. Diagnostic and therapeutic strategies for the early identification and prevention of CTPH are needed.

We sought to evaluate myocardial reperfusion and its prognostic value after percutaneous transluminal coronary angioplasty (PTCA) in patients admitted for cardiogenic shock. Lack of myocardial reperfusion despite restored coronary flow affects the survival of patients with acute myocardial infarction (AMI). Myocardial blush grade (MBG) is an angiographic measure of myocardial perfusion. We assessed MBG in 41 consecutive patients admitted to our department within 12 hours from the onset of AMI and in cardiogenic shock. PTCA was successful in 83% of patients. Thrombolysis In Mycardial Infarction (TIMI) grade 3 flow was demonstrated in 22 patients (53%). MBG 2/3 was found in 14 patients (34%); among them, 12 had TIMI 3 flow. Compared with patients with MBG 2/3, those with MBG 0/1 were older (71 +/- 11 vs 57 +/- 13 years, p = 0.001), had a higher prevalence of diabetes (48% vs 14%, p = 0.04) and hypertension (63% vs 29%, p = 0.04), showed a trend toward longer ischemic time (6.1 +/- 2.4 vs 4.9 +/- 1.1), and had larger enzymatic infarct size (peak creatine kinase 7,690 +/- 3,516 vs 5,500 +/- 2,977 IU/L). Mortality was higher in patients with MBG 0/1 both in the hospital (81% vs 14%, p0.001) and at follow-up (81% vs 29%, p = 0.001). After adjustment by multivariate analysis, MBG 0/1 (odds ratio 16, p = 0.01) and age (odds ratio 3.8/10 years, p = 0.04) were correlated with in-hospital mortality. MBG 2/3 was achieved in a few patients in cardiogenic shock after AMI who were treated with PTCA; this was a strong predictor of in-hospital survival. Also, risk stratification after mechanical revascularization should include assessment of restoration of myocardial reperfusion.

Prospective randomized, multicentre study.Recanalisation of the culprit lesion is the main goal of primary angioplasty for acute myocardial infarction. With the exception of cardiogenic shock, staged procedures are performed in the presence of multivessel disease. The study hypothesis is that with modern non-thrombogenic stents (heparin coated) complete revascularization with multivessel treatment can be safely achieved during the primary angioplasty procedure with a lower need of subsequent revascularization procedures and at a lower cost.PRIMARY: 12-month incidence of repeat revascularization (any revascularization, infarct related artery as well as non-infarct-related artery). SECONDARY: (1) in hospital repeat revascularization, reinfarction and death; (2) total hospital cost (including a 12 months follow-up period).69 patients with ST elevation Acute Myocardial Infarction (AMI),12 hours after symptoms onset, undergoing primary angioplasty, with documented multivessel disease and both culprit lesion and 1 to 3 other lesions suitable for stent implantation. Unbalanced randomization between culprit lesion treatment only (n = 17) and complete multivessel treatment (n = 52, with 71 additional lesions treated).The two groups were well balanced in terms of clinical characteristics, number of diseased vessels and angiographic characteristics of the culprit lesion. In the complete multivessel treatment group 2.36 +/- 0.64 lesions per patient were treated using 2.73 +/- 0.78 heparin coated stents (1.00 lesions and 1.29 +/- 0.61 stents in the culprit treatment group, both p0.001). The duration of the procedure increased from 53 +/- 21 min (culprit treatment group) to 69 +/- 32 min (p = 0.032) and the amount of contrast used from 242 +/- 102 ml (culprit treatment group) to 341 +/- 163 ml (multivessel complete treatment), p = 0.025. A similar low incidence of in-hospital major adverse cardiac events was observed in the 2 groups (0 and 3.8% in culprit and multivessel treatment groups, p = 0.164). The increase in the incidence of new revascularisation in the culprit treatment group at 12 month follow-up was not significant (35 vs 17%, p = 0.247) but was sufficient to compensate the initial higher in-hospital cost, with a similar 12 month hospital cost in the 2 groups (Euro 22,330 +/- Euro 13,653 vs Euro 20,382 +/- Euro 11,671, p = 0.231).Multivessel treatment during primary PTCA was safe in this controlled trial. However, when only the culprit lesion was initially treated, the need for subsequent clinically driven revascularization remained low and no clinical or economical advantages were obtainable with a more aggressive initial approach. In clinical practice, a staged approach to multivessel treatment during primary angioplasty avoids to treat unnecessarily non clinically relevant lesions.

Background: Despite the well-known prognostic impact of systolic dysfunction in unselected patients undergoing percutaneous coronary intervention (PCI), limited data are available on its current predictive role after PCI for unprotected left main disease (ULM). We thus appraised the prognostic role of left ventricular ejection fraction (LVEF) in patients undergoing PCI for ULM with drug-eluting stents (DES). Methods: Consecutive eligible subjects were retrospectively enrolled in a national registry. Patients were divided into three groups: LVEF < 30%, LVEF 30-45%, and LVEF > 45%. Relevant baseline and outcome data were compared with bivariate and multivariable tests. Results: A total of 975 subjects was included (LVEF < 30%: 46, LVEF 30-45%: 208, LVEF > 45%: 721). Patients with LVEF < 30% had several other unfavorable clinical features, including older age and higher EuroSCORE. Adverse event rates were different already at 7 days (p = 0.012 for all-cause death and p = 0.015 for major adverse cardiac events [MACE]), with even more significant trends up to 30 days and at long-term (p < 0.001 for death, and p < 0.001 for MACE). After a median of 18 months, risk of death totaled 39 versus 13 versus 8% (p < 0.001) and risk of MACE 44 versus 24 versus 22% (p = 0.003). Multivariable analyses showed however that reduced LVEF was not an independent predictor of adverse events at any time-point. Conclusions: Whereas reduced LVEF is apparently a significant predictor of adverse events after PCI with DES for ULM, its prognostic impact is mostly due to clustering with other adverse feature

Objective: The influence of left ventricular (LV) dysfunction on survival of patients with severe aortic stenosis is poorly characterized. Few data are available about preoperative predictors of cardiac mortality and LV function recovery after aortic valve replacement of such patients. The aim of our study was to examine the outcome and the preoperative predictors of postoperative cardiac death and of LV function recovery in these patients. Methods: We evaluated 85 consecutive patients with severe aortic stenosis (aortic valve area , 1c m 2 ) and severe depression of LV ejection fraction (EF) , 35% at cardiac catheterization. Among them, 52 underwent aortic valve replacement and they were compared to patients who were not operated on. All patients had a mean clinical follow-up of 53 months and 94% of them had a mean echocardiographic follow-up of 14 months after aortic valve replacement. Results: The mean baseline characteristics included: LVEF 28 ^ 6%, peak-to-peak transvalvular gradient 51 ^ 29 mmHg, aortic valve area 0.63 ^ 0.25 cm 2 . Thirty-three patients did not undergo aortic valve replacement: 32 of them died within 3 years. Fifty-two patients underwent aortic valve replacement and 16 had a concomitant coronary bypass surgery. In-hospital mortality was 8%. Postoperative NYHA functional class changed from 2.84 ^ 0.67 to 1.43 ^ 0.44 (P , 0:001) and LVEF from 29 ^ 6% to 43 ^ 10% (P , 0:001). At follow-up 10 patients died of heart disease. By multivariate analysis, preoperative LV end-systolic volume index (ESVI) was the only covariate of cardiac death (LVESVI/10 ml/m 2 , OR 1.3, CI 1.1 ‐ 1.8, P , 0:028). By using a receiver operating characteristic curve, LVESVI # 90 ml/m 2 was the best cut-off value (sensitivity and specificity 78%) to fit with a better survival (93% vs. 63%, P , 0:01) and with LVEF recovery after aortic valve replacement (EF improved by 15 ^ 10% vs. 8 ^ 5%, P , 0:001). Conclusions: Despite LV dysfunction, aortic valve replacement appears to change drastically the natural history of severe aortic stenosis. Preoperative LV levels predict different postoperative survival rate and LVEF recovery. q 2003 Elsevier B.V. All rights reserved.

The aim of the study was to assess the seasonal variability of non-specific bronchial reactivity (NSBR) evaluated with methacholine in asthmatic farmers allergic to pollens. Twenty farmers (16 male and four female) with allergy to pollens, e.g. Graminae' and Parietaria', entered the study. None of the patients had been previously treated with specific immunotherapy. Patients underwent a methacholine challenge at the first visit and then in the subsequent seasons. Four groups of tests were obtained according to the period when the challenge was performed. Group 1: challenges performed in December, January and February; group 2 in March, April and May; group 3 in June, July and August; group 4 in September, October and November. PD20 values were expressed as the natural logarithm of the cumulative dose of methacholine causing at least a 20% fall in FEV1. Bronchial hyperreactivity was highest in summer, followed by spring and autumn; in winter it was much lower. Multiple group analysis (ANOVA) showed statistically significant differences between the groups (P < 0.01). When the groups were compared individually, statistically significant differences existed only between group 1 (winter) and each of the other groups, respectively 2 (spring) (P = 0.02), 3 (summer) (P = 0.004) and 4 (autumn) (P = 0.02). The results underlined the importance of allergic inflammation in determining changes in NSBR. In the region where the study was carried out (central Italy), the grass and Parietaria pollination lasts from March to November. Therefore, farmers had a progressive increase in NSBR from spring to summer and a decrease in fall as a consequence of the varying pollen concentration in different seasons. The level of allergen exposure is, in fact, the main factor that determines the severity of bronchial inflammation, thus affecting NSBR.

The presence of myocardial injury during non-surgical coronary revascularization has been evaluated by means of highly specific and sensitive biochemical markers. Troponin T, creatine kinase-MB isoenzyme mass concentration, and creatine kinase MB2/MB1 isoform ratio have been determined in 80 patients who underwent coronary revascularization with percutaneous transluminal coronary angioplasty (PTCA). Forty-five patients underwent balloon angioplasty, 15 rotational atherectomy, 10 directional atherectomy, and 10 elective coronary stenting. Serum concentration of the evaluated markers did not increase significantly after 57 uncomplicated revascularization procedures, including 15 rotablation procedures, nor after 8 PTCAs complicated by localized coronary type B and C dissections. Significant elevation of all markers above the upper limits of the reference interval (P0.05) was detected after occlusion of small side branches (0.5 mm diameter) in 5 patients. Creatine kinase MB2/MB1 isoform ratio was the earliest marker to increase. After recanalization of occluded vessels in 8/10 patients with 6-60 days old myocardial infarction only troponin T concentrations increased from a baseline of 0.28 microgram/l to a median peak of 0.80 microgram/l. This increase was statistically not significant (P = 0.12). In conclusion, myocardial damage was not detected following uncomplicated non-surgical revascularization obtained with different techniques. Markers of myocardial injury provide high sensitivity after small side branch occlusion.

Background— Conduction disturbances are relatively common after transcatheter aortic valve implantation. Previous data demonstrated an adverse impact of persistent left bundle-branch block (LBBB) after surgical aortic valve replacement. It is unclear whether new-onset LBBB may also impact the prognosis of patients after transcatheter aortic valve implantation. Methods and Results— Among 1060 patients treated with a CoreValve Revalving System transcatheter aortic valve implantation between October 2007 and April 2011 in high-volume centers in Italy, we analyzed those without LBBB or pacemaker at admission (879 patients [82.9%]). We further excluded those who underwent permanent pacemaker implantation within 48 hours after the procedure (61 patients [7%]), for a final study population of 818 patients. Among them, 224 patients (group A; 27.4%) developed a persistent LBBB and the remaining 594 (group B; 72.6%) did not. Clinical characteristics were similar between groups. A low implantation was significantly more frequent in group A (15% versus 9.8%, P =0.02). No patients were censored before 1 year (median follow-up period 438 days, interquartile range 174–798 days). Survival analyses and inherent log-rank tests showed that LBBB was not associated with higher all-cause mortality, cardiac mortality, or hospitalization for heart failure at 30 days or 1 year. At 30 days, but not at 1 year, group A had a significantly higher rate of pacemaker implantation. Conclusions— In this registry of high-volume centers, persistent LBBB after CoreValve Revalving System transcatheter aortic valve implantation showed no effect on hard end points. On the other hand, LBBB was associated with a higher short-term rate of pacemaker implantation.

Percutaneous balloon mitral valvuloplasty (PBMV) has been shown to induce an immediate increase in the left ventricular end-diastolic volume, which increase, in turn, has been attributed to an increase in left ventricular compliance. We studied 51 patients, 41 women and 10 men, who underwent PBMV, and were in sinus rhythm before and after the procedure. Heart rate did not vary significantly. There were increases in left ventricular end-diastolic volume (97.5 +/- 25.6 vs 112.7 +/- 25.7 ml/m2, P0.001), left ventricular end-diastolic pressure (8.7 +/- 3.0 vs 9.7 +/- 4.3 mmHg, P = 0.04), and both left ventricular systolic pressure and stress (118 +/- 20.5 vs 123 +/- 23.2 mmHg and 468 +/- 129 vs 580 +/- 164 mmHg; P = 0.04 and P0.001, respectively). The elastic stiffness constant did not vary (16.2 +/- 1.9 vs 15.7 +/- 1.9 (dimensionless units), P = 0.2). The increase in volume seemed to be particularly important when the ventricle appeared to be "shrunken" before PBMV. This increase was still present after a 1 year follow up. Thus, PBMV determines an increase in both end-diastolic volume and pressure, so that the left ventricle appears to move along a single pressure-volume curve. This enlargement evokes the Frank Starling mechanism, and improves systolic performance. Since it is still evident after a 1 year follow up, some concern may arise when a simultaneous volume overload is present, as in aortic insufficiency.

Background— Little is known of the prognostic significance of mitral regurgitation (MR) on transcatheter aortic valve replacement (TAVR), the impact of TAVR on MR severity, and the variables associated with possible post-TAVR improvement in MR. We evaluated these issues in a multicenter registry of patients undergoing CoreValve Revalving System–TAVR. Methods and Results— Among 1007 consecutive patients, 670 (66.5%), 243 (24.1%), and 94 (9.3%) presented with no/mild, moderate, and severe MR, respectively. At 1 month after TAVR, patients with severe or moderate MR showed comparable mortality rates (odds ratio, 1.1; 95% confidence interval [95% CI], 0.7–1.55; P =0.2), but both were significantly higher compared with patients with mild/no MR (odds ratio, 2.2; 95% CI, 1.78–3.28; P P =0.02, respectively). One-year mortality was also similar between patients with severe and those with moderate MR (hazard ratio, 1.4; 95% CI, 0.94–2.4; P =0.06) and still significantly higher compared with patients with mild/no MR (hazard ratio, 1.7; 95% CI, 1.2–3.41; P P =0.03, respectively). Severe pulmonary hypertension, atrial fibrillation, and MR more than mild, but not an improvement of ≥1 grade in MR severity, were independent predictors of mortality at 1 year. At 1 year, an improved MR was observed in 47% and 35% of patients with severe and moderate MR, respectively. The rate of low implantation was consistent across groups with improved, unchanged, or worsened MR. A functional type of MR and the absence of severe pulmonary hypertension and atrial fibrillation independently predicted the improvement in MR severity. Conclusions— Baseline MR greater than mild is associated with higher mortality after CoreValve Revalving System–TAVR. A significant improvement in MR was more likely in patients with functional MR and without severe pulmonary hypertension or atrial fibrillation. The improvement in MR did not independently predict mortality.

We appreciate the interest of Prinzen et al about our article,1 but some of their comments need to be addressed. Prinzen et al analyzed a mixed population of patients treated with CoreValve or Edwards Sapien prostheses.2 Of note, their different influence on the cardiac conduction system is well known,3 with the CoreValve being more prone to determine conduction disturbances as a consequence of the larger frame. Accordingly, we decided to specifically focus on the CoreValve, pooling >800 patients, which is more than double the population considered by Prinzen et al. It is clear that the internal and external validity (ie, the extent of systematic biases and the generalizability of the results) are highly affected by the sample size. Prinzen et al excluded patients who underwent pacemaker implantation within 30 days after transcatheter aortic valve replacement, which, in our opinion, makes little …

Background— There is a lack of information on the incidence and predictors of early mortality at 30 days and late mortality between 30 days and 1 year after transcatheter aortic valve implantation (TAVI) with the self-expanding CoreValve Revalving prosthesis. Methods and Results— A total of 663 consecutive patients (mean age 81.0±7.3 years) underwent TAVI with the third generation 18-Fr CoreValve device in 14 centers. Procedural success and intraprocedural mortality were 98% and 0.9%, respectively. The cumulative incidences of mortality were 5.4% at 30 days, 12.2% at 6 months, and 15.0% at 1 year. The incidence density of mortality was 12.3 per 100 person-year of observation. Clinical and hemodynamic benefits observed acutely after TAVI were sustained at 1 year. Paravalvular leakages were trace to mild in the majority of cases. Conversion to open heart surgery (odds ratio [OR] 38.68), cardiac tamponade (OR 10.97), major access site complications (OR 8.47), left ventricular ejection fraction Conclusions— Benefit of TAVI with the CoreValve Revalving System is maintained over time up to 1 year, with acceptable mortality rates at various time points. Although procedural complications are strongly associated with early mortality at 30 days, comorbidities and postprocedural paravalvular aortic regurgitation ≥2+ mainly impact late outcomes between 30 days and 1 year.

Objectives The purpose of this study was to evaluate the performance of CoreValve Revalving System (CRS) (Medtronic, Minneapolis, Minnesota) implantation in patients with failed aortic bioprostheses. Background Transcatheter aortic valve implantation with the CRS is an effective option in high-risk patients with severe aortic stenosis. It may be an option for patients with a failed aortic bioprosthesis, especially when the risk of a surgical redo is deemed prohibitive. Methods CRS “valve-in-valve” implantation was performed in 25 high-risk patients with a failed bioprosthesis. Their mean age was 82.4 ± 3.2 years. New York Heart Association functional classes III and IV were present in 21 and 4 patients, respectively. The logistic EuroSCORE was 31.5 ± 14.8%, whereas the Society of Thoracic Surgeons score was 8.2 ± 4.2. Patients/prostheses were divided in type A (mainly stenotic, n = 9) and type B (mainly regurgitant, n = 16). Results The implantation success rate was 100%. In group A, the peak aortic gradient significantly decreased from 77.6 ± 21.6 mm Hg to 34.6 ± 19.4 mm Hg (p = 0.001). In all but 2 patients in group B, no significant regurgitation was observed post-implantation. No patients died during the procedure. At 30 days, there were 3 deaths (12%), 2 myocardial infarctions (8%), and 3 atrioventricular blocks requiring pacemaker implantation (12%). At a mean follow-up of 6 months, there were another death (survival rate of 84%) and a pacemaker implantation (cumulative incidence of 16%). New York Heart Association functional class improved in all patients to I and II. Conclusions CRS implantation was feasible and effective regardless of the prevalent mode of failure. This finding may significantly affect the treatment of patients with a failed bioprosthesis deemed at a prohibitive risk for surgical redo.

Autoimmune hemolytic anemia (AHA) is a frequent complication of chronic lymphocytic leukemia (CLL). Although the pathogenesis of AHA is still unknown, an imbalance of normal residual T cells is believed to play a central role. Since fludarabine is reported to affect primarily T lymphocytes, we conducted a retrospective study to evaluate the incidence and outcome of AHA in 112 CLL patients treated with fludarabine alone. Eight patients had AHA before therapy; only one achieved remission of both CLL and AHA after fludarabine alone. In the other seven patients, we observed no effect or even a worsening of AHA, although the CLL was responding to fludarabine. Five patients developed AHA from 1 to 19 months after fludarabine therapy while the CLL was responding. One additional patient developed pure red cell aplasia (PRCA) 3 months after starting therapy. Most patients in both groups responded to steroids or other immunosuppressive therapy. The study showed that in these patients, AHA evolved independently of CLL and was not affected by fludarabine.

Percutaneous coronary intervention (PCI) in acute myocardial infarction (AMI) is sometimes complicated by microvascular damage and hemorrhage. Hemoglobin degradation products have magnetic susceptibility effects which help in detecting hemorrhagic AMI by T₂ -weighted cardiac magnetic resonance (CMR) images.To investigate the possibility to detect intramyocardial hemorrhage after AMI and to assess its contribution to the delayed hypoenhanced core on late gadolinium enhancement (LGE) CMR, a feature traditionally referred to as microvascular obstruction.Consecutive patients with AMI who underwent PCI and CMR were investigated. Hypointense zones T₂ -weighted images were labelled as "hemorrhagic" AMI. Areas of late hypoenhancement on LGE CMR were considered as regions of persistent microvascular damage (PMD). Only transmural AMI were considered.A total number of 108 transmural AMI patients were eventually enrolled and divided into two groups according to the presence of hypoenhancement on T₂ images. Thirty-two patients showed an hypointense stria within the high signal intensity zone on T₂ -weighted images; all these patients showed midmural PMD on LGE. Among the remaining 76 patients, only 14 (18.4%) showed PMD in the subendocardial region. The angiographic outcome was worse in patients with hemorrhagic AMI, with a lower prevalence of TIMI 3 (65.6% vs. 96.1%, P = 0.017) and higher prevalence of myocardial blush grade 0 (84.4% vs. 13.2%, P0.001) post-PCI.T₂ -weighted CMR in reperfused AMI allows identification of hemorrhage, related to PMD areas on LGE images and to a worse reperfusion profile on angiography. These features open new avenues of investigation for prognostic assessment of reperfused AMI.

Aims Percutaneous coronary intervention with bare metal stent (BMS) in chronic total coronary occlusions (CTOs) is associated with a higher rate of angiographic restenosis and reocclusion than that observed in subtotal stenoses. Preliminary reports have suggested a better performance of drug-eluting stents in CTO. In this multicentre, randomized trial, we compared the mid-term angiographic and clinical outcome of sirolimus-eluting stent (SES) or BMS implantation after successful recanalization of CTO. Methods and results Patients with CTO older than 1 month, after successful recanalization, were randomized to implantation of SES (78 patients) or BMS (74 patients) in 13 Italian centres. Clopidogrel therapy was prescribed for 6 months. The primary endpoint was in-segment minimal luminal diameter (MLD) at 8-month follow-up. Secondary clinical endpoints included death, myocardial infarction (MI), target lesion revascularization (TLR), and target vessel revascularization (TVR) at 24 months. Patients treated with SES showed, at in-segment analysis, a larger MLD (1.98 ± 0.57 vs. 0.98 ± 0.80 mm, P < 0.001), a lower late luminal loss (−0.06 ± 0.49 vs. 1.11 ± 0.79 mm, P < 0.001), and lower restenosis (9.8 vs. 67.7%, P < 0.001) and reocclusion (0 vs. 17%, P = 0.001) rates. At 24-month follow-up, patients in the SES group experienced fewer major adverse cardiac events (50.0 vs. 17.6%, P < 0.001) mainly due to a lower rate of both TLR (44.9 vs. 8.1%, P < 0.001) and TVR (44.9 vs. 14.9%, P < 0.001). Conclusion In CTO, SES is markedly superior to BMS in terms of restenosis and reocclusion rate, and incidence of repeat revascularization at 24 months. Clinicaltrials.gov identifier: NCT00220558

Hymenoptera venom immunotherapy (VIT) is a safe and effective approach to insect sting allergy. However, after discontinuation, relapses can occur in some patients, especially those with a high occupational risk, and they may need to prolong VIT indefinitely. In order to improve adherence, we propose extending the interval between injections of maintenance VIT (MVIT).To evaluate the safety, efficacy, and patient acceptance of a 3-month interval between MVIT injections in a group of Hymenoptera-allergic patients who are occupationally exposed to insect stings.We included 72 patients with severe systemic reactions to Hymenoptera stings. MVIT was administered for 4 years at intervals increasing up to 3 months and then continued for a further 2 years. Patients were informed of the risk of relapse after discontinuation and of the need for indefinite treatment at 3-month intervals.During the 3-month interval maintenance phase, only 235 local reactions (17.8%) were observed in 17 patients. Sixty patients experienced 125 field re-stings and only 1 experienced a systemic reaction with generalized urticaria.The study confirms that the conventional MVIT interval of 4 to 6 weeks can be extended to 3 months in most patients with no adverse events, while maintaining safety and efficacy, improving adherence, and guaranteeing safe continuation of professional activity.

Udgivelsesdato: 2010-Jun AIMS: The European PLAATO (Percutaneous Left Atrial Appendage Transcatheter Occlusion) study was performed to determine the safety and efficacy of left atrial appendage occlusion by catheter technique. Embolic stroke due to atrial fibrillation is a common observation, especially in the elderly. Most thrombi in atrial fibrillation form in the left atrial appendage (LAA), its occlusion may therefore reduce the incidence of stroke in these patients. METHODS AND RESULTS: One hundred and eighty patients with non-rheumatic atrial fibrillation and contraindication to warfarin therapy were enrolled in the PLAATO study. Patients were eligible if they had a?history of transient ischaemic attack (TIA) or stroke or at least two independent risk factors for stroke such as age > or =75 years, hypertension, congestive heart failure or diabetes. The primary endpoint was LAA closure as determined by transesophageal echocardiography (TEE) two months after the procedure and stroke rate at 150 patient years. Left atrial appendage occlusion was successful in 162/180 patients (90%, 95% CI 83.1% to 92.9%). Two patients died within 24 hours of the procedure (1.1%, 95% CI 0.3% to 4%). Six cardiac tamponades were observed (3.3%, 95% CI 1.5% to 7.1%). In two cases, surgical drainage of the tamponade was necessary (1.1%, 95% CI 0.3% to 4%). In one patient, the device that was chosen was too small and embolised into the aorta after its release (0.6%, 95% CI 0.1% to 3.1%). It was snared and replaced without further complications. Successful occlusion of the LAA was achieved in 126/ 140 (90%, 95% CI 83.5% to 94.2%) of patients as noted by TEE at the two months follow-up. In a follow-up time of 129 documented patient years, three strokes occurred (2.3% per year). The expected incidence of stroke according to the CHADS2-Score was 6.6% per year. The trial was halted prematurely during the follow-up phase for financial considerations. CONCLUSIONS: Left atrial appendage closure is relatively safe and effective. However, severe complications can occur. It might become an alternative for atrial fibrillation patients who are ineligible for long-term anticoagulation therapy.

Aims: Percutaneous coronary intervention (PCI) is increasingly being used for unprotected left main (ULM) disease. Limited data are available on sex-related differences in this setting. We investigated gender-associated differences in patients undergoing stent-based PCI for ULM. Methods and results: We analysed baseline, procedural and long-term data of patients with ULM undergoing stent-based PCI at participating centres. The primary end-point was the long-term rate of major cardiovascular events rate (MACE, i.e., the composite of death, myocardial infarction, or target lesion revascularisation). The study population included 1,452 cases, with 27.8% females and 72.2% males. Women were older, more frequently diabetic, hypertensive or presenting with an acute coronary syndrome, and thus with a higher EuroSCORE, but were less commonly treated with drug-eluting stents (DES), in comparison to men (all p

Although angiographic perfusion has been traditionally evaluated by myocardial blush grade (MBG), pathophysiologic features underlying different MBG and the persistent blush, traditionally called staining, have been poorly explained. The aim of the study was to evaluate the correlation between MBG and morphologic aspects on cardiac magnetic resonance (CMR).Myocardial blush grade and morphologic aspects on contrast-enhanced CMR, with special reference to staining phenomenon and persistent microvascular damage (PMD), were evaluated in a consecutive series of patients with acute myocardial infarction (AMI) treated by primary percutaneous coronary intervention.A total number of 294 AMI patients were enrolled and classified into 2 groups, that is, MBG 0/1 (115, 39%) and MBG 2/3 (179, 61%), according to the angiographic profile. By comparing MBG 0/1 versus MBG 2/3 patients, the former exhibited a larger enzymatic infarct size (P.001) and a greater infarct size index (P.001) and PMD (P.001). In the MBG 0/1 group, a subgroup of 51 patients with staining phenomenon (MBG 0 staining) was also identified, with a worse CMR profile as PMD (P.001). Multivariate analysis confirmed the strong association between MBG 0/1 and mean number of segments with transmural necrosis (odds ratio 1.62, 95% CI 1.17-2.24, P = .003) and PMD index (odds ratio 3.13, 95% CI 1.19-8.29, P = .021).In AMI patients treated by primary percutaneous coronary intervention, angiographic parameters of impaired reperfusion correlate with PMD as detected by contrast CMR. Among patients with MBG 0, the presence of the so-called staining phenomenon identifies a subgroup of patients with more severe PMD.

Aims To compare long-term clinical outcome following drug-eluting stents (DES) or bare-metal stents (BMS) implantation on lesions located at the ostium or the shaft of the left main in a large real-world population. The advent of DES decreased the risk of unprotected left main coronary artery (ULMCA) restenosis when compared with BMS, but it is unclear if this advantage continues when non-bifurcational lesions are considered. Methods and results The GISE-SICI registry is a retrospective, observational multicentre registry promoted by the Italian Society of Invasive Cardiology in which 19 high-volume participating centres enrolled 1453 consecutive patients who underwent percutaneous coronary intervention on ULMCA between January 2002 and December 2006. From the registry, a total of 479 consecutive patients with ostial and shaft lesions who underwent DES ( n = 334) or BMS ( n = 145) implantation were analysed with extensive multivariable and propensity score adjustments. At 3-year follow-up, risk-adjusted survival rates were higher in patients treated with DES than in those treated with BMS. The adjusted hazard ratio (HR) for the risk of mortality after DES implantation relative to BMS implantation was 0.37 (95% CI: 0.15–0.96, P = 0.04). The adjusted HR for the risk of cardiac mortality was 0.31 (95% CI: 0.09–1.04, P = 0.06). The adjusted 3-year rates of target lesion revascularization (TLR) were not significantly lower in the DES group than in the BMS group ( P = 0.60). Conclusion In a large population of patients with lesions located at the ostium or the shaft of the left main in a real-world setting, DES were associated with favourable clinical outcomes when compared with BMS, although there was no evidence of a significant reduction in TLR with DES vs. BMS.

Aims We sought to identify predictors of distal embolization (DE) occurring during primary percutaneous coronary intervention (p-PCI) as well as to assess its impact on both myocardial reperfusion and necrosis, according to time-to-treatment. Methods and results Clinical and angiographic characteristics were prospectively assessed in 400 consecutive patients who underwent p-PCI, in order to identify predictors of DE. The impact of DE on Thrombolysis in Myocardial Infarction (TIMI) flow, myocardial blush, and troponin I (TnI) was assessed according to symptom onset-to-balloon time. DE occurred in 64 (16%) patients and did not change with time-to-treatment ( P = 0.87). The occlusion pattern of infarct-related artery (IRA), treatment of right coronary artery, higher TIMI thrombus score, longer lesion, and large IRA diameter were predictors of DE. The rate of TIMI 0/1 and myocardial blush 0/1 was higher in patients exhibiting DE when time-to-treatment was ≤6 h ( P < 0.0001), while TnI was higher in patients with DE when time-to-treatment was

Aims In this study, we compared the cumulative risk of major adverse cardiac events (MACE) of patients with distal unprotected left main coronary artery (ULMCA) stenosis with those of patients with ostial and midshaft lesions treated with drug-eluting stent (DES). Methods and results The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centres. We enrolled 1111 patients with ULMCA stenosis treated with DES. Major adverse cardiac events were defined as death, myocardial infarction, and target lesion revascularization. Three hundred and thirty-four patients had ostial or midshaft lesions (group 1) and 777 bifurcations (group 2). The adjusted hazards ratio of the risk of 2 year MACE of patients in group 2 vs. patients in group 1 was 1.50 ( P = 0.024). However, we observed that there was a significant difference between patients with bifurcations treated with two stents and those in group 1 ( P = 0.001), but not between patients with bifurcations treated with one stent and those in group 1 ( P = 0.38). Conclusion Patients with bifurcations have a worse outcome than patients with ostial and midshaft lesions. However, the technique used to treat bifurcations has a significant impact on clinical outcomes.

ObjectivesOur aim was to assess the safety and feasibility of the retrograde trans-subclavian approach to transcatheter aortic valve implantation (TAVI) in selected high-risk patients with aortic stenosis (AS) and severe peripheral vasculopathy.BackgroundTAVI is an emerging therapeutic option to treat inoperable/high-risk patients affected by symptomatic AS. However, these patients are also often affected by severe iliac-femoral arteriopathy, rendering the transfemoral approach unemployable for percutaneous revalving procedure.MethodsFrom among those patients in our department between May 2007 and December 2008, who were refused surgical aortic valve replacement because of high surgical risk and were ineligible for transfemoral percutaneous aortic valve replacement, we scheduled 3 for TAVI by the subclavian approach. Procedures were performed by a combined team of cardiologists, cardiac surgeons, and anesthetists in the catheterization laboratory. The III generation CoreValve Revalving System (CoreValve Inc., Irvine, California) with an 18-F delivery system was introduced in all cases by the left subclavian artery.ResultsProsthetic valves were successfully implanted in all 3 cases, leading to a fall in transvalvular gradient without significant paravalvular regurgitation. No intraprocedural or periprocedural complications occurred. Two patients developed an atrioventricular block requiring the implantation of a permanent pacemaker. All patients were discharged in asymptomatic status, with good prosthesis performance. No adverse events occurred within the 3-month follow-up.ConclusionsTAVI by subclavian retrograde approach seems safe and feasible in inoperable/high-risk patients with AS and peripheral vasculopathy, who are neither eligible for surgical valve replacement nor transfemoral percutaneous aortic valve implantation. Further studies are needed to evaluate the long-term efficacy of this new therapy.

Objectives Persistence of ST-segment elevation after myocardial infarction has been ascribed to left ventricular aneurysm development. However, its pathophysiological basis is still undefined. This study sought to evaluate myocardial structural and functional abnormalities underlying persistent ST-segment elevation, using contrast-enhanced magnetic resonance imaging. Methods Forty patients treated with primary angioplasty for a first anterior myocardial infarction underwent contrast-enhanced magnetic resonance imaging. Persistent ST-segment elevation was defined as ST-segment elevation of at least 2 mm in two or more leads on predischarge electrocardiogram. The presence and extent of myocardial necrosis and persistent microvascular damage, as well as wall motion abnormalities, were assessed by contrast-enhanced magnetic resonance imaging. Results At contrast-enhanced magnetic resonance imaging, patients with persistent ST-segment elevation had higher infarct size index (P = 0.02) and showed transmural necrosis (P = 0.03) and persistent microvascular damage (P = 0.003) more often. Left ventricular aneurysm was seen more frequently in patients with ST-segment elevation (P = 0.08). In a multivariate model, persistent microvascular damage was the only independent predictor of persistent ST-segment elevation (odds ratio 3.13, confidence interval 1.21–8.10, P = 0.01). Conclusion Persistent ST-segment elevation after anterior myocardial infarction is related to a larger extent of transmural necrosis and persistent microvascular damage as assessed by contrast-enhanced magnetic resonance imaging. However, the presence of microvascular damage seems to be the most powerful determinant of persistent ST-segment elevation.

Background: Few data are available on diabetic patients undergoing percutaneous coronary intervention (PCI) in the context of unprotected left main coronary artery (ULMCA) disease. The main goal of this study was to present the long-term relative benefits of using drug-eluting stent (DES) instead of bare-metal stent (BMS) for diabetic patients submitted to percutaneous ULMCA treatment in a large real world multicenter registry. Methods: The GISE-SICI registry is a retrospective, observational multicenter registry promoted by the Italian Society of Invasive Cardiology in which 19 high-volume participating centers enrolled 1,453 consecutive patients who underwent PCI on ULMCA between January 2002 and December 2006. From the registry, a total of 398 consecutive patients with diabetes mellitus who underwent DES (n = 321) or BMS (n = 77) implantation were analyzed, with extensive multivariable adjustments. Results: At 3-years, use of DES in diabetic patients resulted in no significant differences with respect to death (HR 0.56, 95% CIs 0.24–1.28), myocardial infarction (HR 0.82, 95% CIs 0.21–3.26), and the composite end-point of death or myocardial infarction (HR 0.56, 95% CIs 0.27–1.20). Conversely, DES were associated with significant reduction of target lesion revascularization (TLR, HR 0.33; 95% CIs 0.14–0.80, P = 0.001) rates. Conclusions: Patients presenting with ULMCA disease in the context of diabetes mellitus who are treated with stent-supported PCI have a significant reduction in the rate of TLR with no increased risk of death or myocardial infarction. © 2009 Wiley-Liss, Inc.

Data are limited about the relative efficacy of drug-eluting stents (DESs) versus bare-metal stents (BMSs) for the treatment of unprotected left main coronary artery (ULMCA) stenosis. The survey promoted by the Italian Society of Invasive Cardiology on ULMCA stenosis was an observational study involving 19 high-volume Italian centers of patients with ULMCA stenosis treated using percutaneous coronary intervention (PCI). From January 2002 to December 2006, of 1,453 patients identified with ULMCA stenosis treated with PCI, 1,111 were treated with DESs and 342 were treated with BMSs. During a 2-year follow-up, risk-adjusted survival free from cardiac death was significantly higher in patients treated with DESs than in those treated with BMSs. The propensity-adjusted hazard ratio for risk of 2-year cardiac mortality after DES versus BMS implantation was 0.49 (95% confidence interval 0.32 to 0.77). The benefit of DESs in reducing cardiac mortality was obtained in the period from 3 to 6 months and maintained up to 2 years. In conclusion, for patients with ULMCA stenosis undergoing PCI, DES implantation was associated with higher adjusted rates of 2-year survival free from cardiac death. The benefit of DESs in reducing cardiac mortality was obtained in the period in which clinical manifestations of restenosis usually peak.