Sirolimus-Coated Balloon in an All-Comer Population of Coronary Artery Disease Patients: The EASTBOURNE Prospective Registry.

BACKGROUND: Drug-coated balloons (DCB) represent 1 of the most promising innovations in interventional cardiology and may represent a valid alternative to drug-eluting stents. Currently, some sirolimus-coated balloons (SCB) are being investigated for several coronary artery disease applications. OBJECTIVES: This study sought to understand the role of a novel SCB for the treatment of coronary artery disease. METHODS: EASTBOURNE (All-Comers Sirolimus-Coated Balloon European Registry) is a prospective, multicenter, investigator-driven clinical study that enrolled real-world patients treated with SCB. Primary endpoint was target lesion revascularization (TLR) at 12 months. Secondary endpoints were procedural success, myocardial infarction (MI), all-cause death, and major adverse clinical events (a composite of death, MI, and TLR). All adverse events were censored and adjudicated by an independent clinical events committee. RESULTS: A total population of 2,123 patients (2,440 lesions) was enrolled at 38 study centers in Europe and Asia. The average age was 66.6 ± 11.3 years, and diabetic patients were 41.5%. De novo lesions (small vessels) were 56%, in-stent restenosis (ISR) 44%, and bailout stenting occurred in 7.7% of the patients. After 12 months, TLR occurred in 5.9% of the lesions, major adverse clinical events in 9.9%, and spontaneous MI in 2.4% of the patients. The rates of cardiac/all-cause death were 1.5% and 2.5%, respectively. The primary outcome occurred more frequently in the ISR cohort (10.5% vs 2.0%; risk ratio: 1.90; 95% CI: 1.13-3.19). After multivariate Cox regression model, the main determinant for occurrence of the primary endpoint was ISR (OR: 5.5; 95% CI: 3.382-8.881). CONCLUSIONS: EASTBOURNE, the largest DCB study in the coronary field, shows the safety and efficacy of a novel SCB in a broad population of coronary artery disease including small vessels and ISR patients at mid-term follow-up. (The All-Comers Sirolimus-Coated Balloon European Registry [EASTBOURNE]; NCT03085823).

Conduction abnormalities after transcatheter aortic valve implantation.

In the last few years, transcatheter aortic valve implantation (TAVI) has become an alternative procedure in patients with severe aortic stenosis and high risk for surgical aortic replacement. Due to the anatomic correlation between aortic valve structure and conduction system of the heart, one of the most common complications after TAVI is conduction system disturbances which including bundle branch block, complete heart block and need for permanent pacemaker implantation. Although these disturbances are usually not lethal, they may have a great influence on patients' state and long term-survival. Several risk factors for conduction disturbances have been identified which including age, anatomy of the heart, periprocedural factors, type of implanted valve, preexisting abnormalities and comorbidities. As this technique becomes more familiar to physicians, patients should be carefully screened for risk factors for the development of conduction abnormalities after TAVI in order to provide effective prevention and proper treatment.

Four-year clinical results of transcatheter self-expanding Medtronic CoreValve implantation in high-risk patients with severe aortic stenosis.

BACKGROUND: transcatheter aortic valve implantation (TAVI) has emerged as an alternative to surgical aortic valve replacement for patients with severe aortic stenosis considered inoperable or at high operative risk, but the long-term outcome remains unknown. HYPOTHESIS: we assessed the 4-year clinical and echocardiographic outcomes of patients undergoing TAVI with the self-expanding Medtronic CoreValve prosthesis. METHODS: sixty-three patients (mean age 80 ± 6 years) with severe aortic stenosis (AS) at high risk for surgical aortic valve replacement (Logistic EuroSCORE 28.8 ± 10.9%) were included in this study. RESULTS: all-cause cumulative mortality at 1, 2, 3 and 4 years was 14.3, 25.4, 28.6 and 36.5%, respectively. The cumulative incidence of documented major stroke at 4 years was 6.3%. In survivors, there was a significant improvement in functional status at 4 years. Paravalvular leak (trivial/mild to moderate) was observed in the majority of patients post-TAVI with no case of progression to severe regurgitation at 4-year follow-up. In multivariate analysis, independent predictor for increased all-cause mortality was left ventricular ejection fraction <40% (HR: 5.347, 95% CI: 1.126-25.381, P = 0.035). CONCLUSION: our study demonstrated favourable long-term (4 years) outcomes after successful TAVI using the third-generation Medtronic CoreValve device.

Management of Coronary Artery Disease and Conduction Abnormalities in Transcatheter Aortic Valve Implantation.

OPINION STATEMENT: Transcatheter aortic valve replacement (TAVR) is an expanding, catheter-based technology that allows the implantation of a prosthetic valve without requiring open heart surgery for the treatment of severe aortic stenosis (AS). The frequency of coronary artery disease (CAD) in patients (pts) with severe AS undergoing surgical treatment ranges from 30 to 50 %. This tends to be higher in pts undergoing TAVR with a prevalence of 49-76 % and is more prevalent with older age and the fact that TAVR is commonly performed in high-risk groups with more advanced cardiovascular disease. The overall influence of CAD on TAVR procedural outcomes remains controversial, and the management of concomitant artery disease is still under discussion. There are three major issues that must be addressed: the impact of CAD, optimal timing of percutaneous coronary intervention (PCI) and TAVR, and extent of revascularization. Today, TAVR is commonly performed as a stand-alone procedure with variable degrees of concomitant CAD tolerated without intervention. One of the major potential complications with TAVR is the damage to the conduction system. The requirement of permanent pacemaker (PM) implantation ranges from 9 to 49 % of cases with a mean of ~20 %, whereas surgical aortic valve replacement (sAVR) is associated with a complete heart block that requires permanent PM in 3-12 % of cases. Reports have demonstrated an increased incidence of conduction damage in patients undergoing TAVR with the CoreValve (Medtronic Minneapolis, MN, USA) prosthesis (mean 20.8 %, range 9.3-30.0 %) compared with the Edwards SAPIEN (Edwards Lifesciences LLC; Irvine, CA, USA) prosthesis (mean 5.4 %, range 0-10.1 %). Factors predicting PM implantation include preexisting bundle branch block (BB) or conduction abnormalities. The prognostic significance of new left bundle branch block (LBBB) after TAVR is unclear. In the future, new valve designs may improve the incidence of permanent PM implantation after TAVR.

Cardiovascular magnetic resonance and computed tomography in the evaluation of aneurysmal coronary-cameral fistula.

Coronary artery fistulas represent abnormal communications between a coronary artery and a major vessel like venae cavae, pulmonary arteries or veins, the coronary sinus, or a cardiac chamber. The latter is called coronary cameral fistula is a rare condition and is most of the times congenital but can be also post traumatic or post surgical, especially after cardiovascular interventional procedures. Most patients are asymptomatic and coronary-cameral fistulae are discovered incidentally during angiographic evaluation for coronary vascular disorders, while other patients have a clinical presentation ranging from angina pectoris to heart failure. In this article, we report a rare case of an aneurysmal right coronary cameral fistula draining into the left ventricle. Echocardiography usually represents the first diagnostic imaging approach, but often due to a poor acoustic window may not show the entire course of the fistula which is crucial for the final diagnosis. ECG-gated cardiovascular CT may play an important role in the evaluation of the origin, course, termination and morphology of the fistula, its relation to the adjacent anatomical structures as well as the morphology and contractility of the heart. Cardiac MRI instead plays an additional crucial role regarding not only the above mentioned factors but also in estimating the blood flow within the fistula, providing more detailed information about the cardiac function but also about myocardial wall viability.

The role of TNF-α, Fas/Fas ligand system and NT-proBNP in the early detection of asymptomatic left ventricular dysfunction in cancer patients treated with anthracyclines.

BACKGROUND: Anthracycline-induced cardiotoxicity typically presents as congestive heart failure (CHF). As immuno-inflammatory activation and apoptosis are important mechanisms in the process of heart failure, the use of biomarkers that could detect cardiovascular toxicity before the clinical presentation is of great importance. We studied whether sTNF-a, sTNF-RI, sTNF-RII, Fas/FasLigand system and NT-proBNP associate with early cardiac dysfunction in patients receiving cardiotoxic drugs. METHODS: Two groups of breast cancer patients-group A with metastatic disease under chemotherapy with epirubicin and group B with no residual disease under a less cardiotoxic regimen-as well as healthy women were included in this prosprective study. NT-proBNP, sTNF-a, sTNF-RI, sTNF-RII, sFas, sFas-Ligand and left ventricular ejection fraction (LVEF) were determined in all patients before and after the completion of chemotherapy. RESULTS: In Group A, an increase in sFas levels (p < 0.001), a decrease in the sFasL levels (p = 0.010), an NT-proBNP increase (p < 0.001) and a significant reduction of LVEF (p < 0.001) was recorded post-chemotherapy. The decrease in LVEF correlated significantly with the increase in sFas, the decrease in sFasL and the rise in NT-proBNP levels. In Group B, TNF-RI levels were higher (p = 0.024) and mean sFas-L levels lower (p = 0.021) post chemotherapy with no LVEF drop. Two of group A (7.6%) patients developed symptomatic CHF 12 and 14 months respectively after the end of chemotherapy. CONCLUSION: SFas, sFas-L and NT-proBNP correlate with reductions in LVEF and could be used as sensitive biochemical indices for the detection of asymptomatic left ventricular dysfunction in cancer patients under cardiotoxic chemotherapy.

Anesthetic management of patients undergoing transcatheter aortic valve implantation.

OBJECTIVE: To compare 2 anesthetic techniques, general anesthesia or monitored anesthesia care, performed by the same cardiac anesthesiologists for transcatheter aortic valve implantation in the authors' institution. DESIGN: A retrospective study. SETTING: A single specialized cardiac surgery center. PARTICIPANTS: Ninety-eight patients with severe aortic valve stenosis and a high logistic EuroSCORE considered not eligible to undergo conventional aortic valve replacement. INTERVENTION: General anesthesia or monitored anesthesia care. MEASUREMENTS AND MAIN RESULTS: General anesthesia was used in 57 and monitored anesthesia care in 41 patients. The authors compared the following parameters: Duration of procedure, transfusion requirements, cardiac indices, superior vena cava saturation (ScVO2) before and after the aortic valve implantation, hospital length of stay and 30-day mortality. The only significant differences between the groups concerned were the duration of anesthesia (p<0.001) and ScVO2 values. Anesthesia duration was prolonged significantly when general anesthesia was administered, and ScVO2 was significantly higher both before and after the valve implantation in the general anesthesia group. Thirty-day mortality was 5.3% in the general anesthesia group and 4.9% in the monitored anesthesia group. CONCLUSIONS: It would appear that both anesthetic techniques may be used for patients with a high logistic EuroSCORE undergoing transcatheter aortic valve implantation.

Idiopathic pulmonary arterial hypertension in a young patient with the Cohen syndrome.

We admitted a 16-year-old boy with the Cohen syndrome to our institution for increasing dyspnoea. Investigations revealed idiopathic pulmonary hypertension. He was commenced on bosentan and oral anticoagulation and was followed up for nearly 7 years, during which he was readmitted for dynamic measurements of pulmonary artery pressure. Despite initial improvement, the right heart pressures increased again and sildenafil was added. His final hospitalisation was due to increasing breathlessness and episodes of syncope. The addition of prostacyclin conferred no reduction in pulmonary artery pressure. The patient suffered a cardiac arrest and remained intubated for 2 weeks, during which Klebsiella pneumonia and superinfection with the H1N1 swine flu virus occurred. The patient died due to multi-organ failure, nearly 7 years after his initial diagnosis. The Cohen syndrome, its phenotype and clinical findings, and the incidence and treatment of pulmonary hypertension are discussed.

Transcatheter aortic valve implantation: restoring the qualities of life in old age.

Transcatheter aortic valve implantation (TAVI) is a tremendous therapeutic advance for patients with severe aortic stenosis and high-surgical risk. Since TAVI-treated patients are elderly with multiple co-existing conditions, limited life expectancy and disproportionate health-care expenditures, the aspect of the health-related quality of life (HRQoL) benefits becomes of fundamental importance. Based on recent evidence, TAVI appears to improve significantly HRQoL measures compared with optimal standard care, which are restored to age-adjusted population norms over time.

Unprotected left main distal bifurcation lesion.

Left main coronary artery disease is a high-risk condition with significant mortality. Currently, bypass surgery is considered the gold-standard treatment for unprotected left main disease. The introduction of drugeluting stents for the treatment of coronary artery disease has proved to reduce the rates of restenosis and, consequently, the need for repeat revascularisation; therefore, recently, percutaneous coronary intervention in the unprotected left main using drug-eluting stents has been considered another therapeutic option for patients at high risk for bypass surgery, or for patients who simply refuse bypass surgery. Based on the updated guidelines on myocardial revascularisation of the European Society of Cardiology, treating left main lesions by angioplasty is feasible and safe in selected patients. In this case report we demonstrate the successful implantation of drug-eluting stents for the treatment of an unprotected left main bifurcation lesion in an 85-year-old patient with high perioperative risk.

Anomalous origin of coronary arteries: when one sinus fits all.

A right coronary artery origin from the left coronary sinus and a left coronary origin from the right sinus although rarely encountered during routine cardiac catheterization, they represent two relatively common autopsy findings in young patients suffering sudden cardiac death. The interarterial course of the aberrant artery, between the aortic root and the pulmonary artery has been considered as a malignant variant, because of the higher risk of myocardial ischemia and sudden death. We present two rare cases of ectopic coronary origin from the opposite sinus of Valsalva.

Long-term quality of life improvement after transcatheter aortic valve implantation.

BACKGROUND: Transcatheter aortic valve implantation (TAVI) is a novel therapeutic option for severe aortic stenosis in old patients with high surgical risk. The aim of this study was to assess changes in quality of life (QoL) along with functional status and late survival after this procedure. METHODS: Thirty-six consecutive patients (80.5 ± 5.9 years, 21 men and 15 women) with a logistic Euroscore of 29.7 ± 13.7 underwent TAVI using the 18-Fr CoreValve prosthesis. Aortic valve prosthesis was inserted retrograde using a femoral or a subclavian arterial approach. QoL was evaluated by administering the Short Form 36 (SF-36) tool and the shorter SF-12 version 2 (SF-12v2) questionnaires before and 1-year after TAVI. RESULTS: TAVI was successfully performed in all patients. The estimated 1-year overall survival rate using Kaplan-Meier method was 68%. One-year follow-up also showed a marked improvement in echocardiographic parameters (peak gradient 76.2 ± 26.1 vs 15.4 ± 7.8 mm Hg, P < .001; aortic valve area 0.7 ± 0.1 vs 2.6 ± 2.7 cm(2), P < .001) with a significant change in New York Heart Association class (3 ± 0.7 vs 1.2 ± 0.4, P < .001). Both preprocedural summary SF-36 and SF-12v12 physical and mental scores showed a significant improvement 1 year after TAVI (21.6 vs 46.7, P < .001; 42.9 vs 55.2, P < .001; 22 vs 48.9, P < .001; 43.3 vs 52.2, P < .001, respectively). CONCLUSIONS: Our results show a marked 1-year clinical benefit in functional status and physical and mental health in patients who underwent TAVI.

Cytokine gene polymorphisms are associated with markers of disease severity and prognosis in patients with idiopathic dilated cardiomyopathy.

AIMS: To identify potential genetic associations of five cytokine gene polymorphisms with disease severity and prognosis in patients with idiopathic dilated cardiomyopathy (DCM). METHODS AND RESULTS: Eighty patients with DCM were genotyped for transforming growth factor beta1 (TGF-ß1)+869 T/C (codon10 Leu→Pro), TGF-ß1 +915 G/C (codon25 Arg→Pro), interleukin (IL)-6 -174G/C, tumor necrosis factor-alpha (TNF-α) -308A/G, interferon-gamma (IFN-γ) +874T/A, IL-10 -1082A/G, IL-10 -819T/C and IL-10 -592A/C gene polymorphisms. In homozygous TT patients for TGF-ß1 +869 T/C polymorphism mean VO(2) max was significantly higher than in CC homozygous patients (25.67±6.73ml/kg/min vs. 20.29±6.35 ml/kg/min, p = 0.046), which remained significant only for patients younger than 39 years old after adjusting for age and sex (p = 0.009). C carriers of TGF-ß1 +915 G/C polymorphism are 4.2 times more likely to be in a worse NYHA stage (III-IV) than non C carriers [OR: 4.25, 95% CI (1.53-11.80), p = 0.006]. Patients GG homozygous for IL-6 -174G/C polymorphism presented greater left ventricle end-systolic (p = 0.018) and end-diastolic (p = 0.04) diameters in comparison to the CC homozygous. The AA homozygote for IFN-γ +874T/A polymorphism (p = 0.02) and the combination of the TGF-ß1 +869 T/C and TGF-ß1 +915 G/C genotypes were associated with adverse outcome (p = 0.014). CONCLUSION: Specific cytokine gene polymorphisms seem to be associated with worse prognosis as well as with measures of disease severity in DCM.

Transcatheter aortic valve implantation, patient selection process and procedure: two centres' experience of the intervention without general anaesthesia.

INTRODUCTION: transcatheter aortic valve implantation (TAVI) is an emerging technique for the treatment of aortic stenosis. With the advent of percutaneous suture devices for the access point and prosthesis delivery systems of smaller diameter, TAVI has become a truly percutaneous procedure: percutaneous aortic valve replacement (PAVR). Thus, PAVR may be conducted without general anaesthesia (GA). METHODS: We report two centres' experience from PAVR without GA. CoreValve aortic bioprostheses were utilised. The patient selection process and PAVR procedure are described in detail. RESULTS: a total of 30 patients (pts) were treated with PAVR. In 4 pts correction of the initial malposition of the prosthesis required a special technique (2 pts: "snare"; 2 pts: "removing and reinserting"). At 1-month follow up, haemodynamic and clinical improvements were observed: left ventricular ejection fraction increased from 50.8 ± 9.3% to 54.3 ± 8.3% (p=0.02); peak aortic valve gradient decreased from 90.3 ± 26.4 mmHg to 14.8 ± 9.7 mmHg, (p<0.001); NYHA functional class decreased from 3.53 ± 0.93 to 1.45 ± 0.94 (p<0.001). Overall 1-month mortality was 3.3% (1 patient died). CONCLUSION: PAVR without general anaesthesia is a feasible technique, however the role of anaesthesiologists is still important.

Short and long term anti-inflammatory effects of bosentan therapy in patients with pulmonary arterial hypertension: relation to clinical and hemodynamic responses.

OBJECTIVE: We sought to investigate the short- and long- term effects of bosentan therapy on endothelial, inflammatory and fibrotic markers in patients with pulmonary arterial hypertension (PAH) and the relation to clinical and hemodynamic responses. METHODS: We studied 16 patients with moderate-severe idiopathic PAH, in WHO functional class II-IV, despite conventional treatment. Patients received additional treatment with bosentan, 62.5 mg twice daily for 1 month, followed by 125 mg twice daily for 11 months. Study endpoints included 6-min walking distance (6MWD), mean pulmonary artery pressure (mPAP), pulmonary vascular resistance (PVR) and plasma levels of intracellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), IL-6 and brain natriuretic peptide (BNP). Patients were assessed at baseline, 2 months and 12 months after initiation of bosentan. RESULTS: At 2 months there was an improvement in 6MWD (p < 0.001) and functional class (p < 0.001) and a marked fall in PVR (p < 0.001), ICAM-1 (p < 0.001), IL-6 (p < 0.001)and BNP (p = 0.001). At 12 months, 6MWD was further improved (p < 0.001), PVR remained significantly improved (p < 0.001), mPAP was significantly decreased (p < 0.001) and ICAM-1, IL-6 and BNP remained significantly lower (p < 0.001). Significant correlations were found between changes in ICAM-1 and cardiac index (r = 0.59, p = 0.01), IL-6 and PVR (r = 0.51, p = 0.04), BNP and 6MWD (r = -0.53, p = 0.03) and BNP and PAP (r = 0.51, p = 0.04) between 2- and 12-months treatment. CONCLUSIONS: In patients with moderate-severe PAH, the addition of bosentan to therapy, exerts favorable anti-inflammatory effects, which are associated with clinical and hemodynamic improvement.