Infective endocarditis in a cohort of adult CHD patients.

BACKGROUND: CHD increases the risk of infective endocarditis due to the substrate of prosthetic materials and residual lesions. However, lesion-specific and mortality risks data are lacking. We sought to analyse clinical course and mortality of infective endocarditis in a cohort of adult CHD. METHODS: Retrospective analysis of all cases of proven and probable infective endocarditis (Duke's criteria) followed in our adult CHD clinic between 1970 and August, 2021. Epidemiological, clinical and imaging data were analysed. Predictors of surgical treatment and mortality were assessed using regression analysis. RESULTS: During a mean follow-up of 15.8 ± 10.9 years, 96 patients had 105 infective endocarditis episodes, half with previous cardiac surgery (corrective or palliative). The most frequent diagnoses were: ventricular septal defect, bicuspid aortic valve, Tetralogy of Fallot and pulmonary atresia. The site of infection was identified by echocardiography in 82 episodes (91%), most frequently in aortic (n = 27), tricuspid (n = 15), and mitral (n = 13) valves. Blood cultures were positive in 79% of cases, being streptococci (n = 29) and staphylococci (n = 23) the predominant pathogens. Surgery was necessary in 40% and the in-hospital mortality was 10.5%, associated with heart failure (p < 0.001; OR 13.5) and a non-surgical approach (p = 0.003; OR 5.06). CONCLUSIONS: In an adult CHD cohort, infective endocarditis was more frequent in patients with ventricular septal defect and bicuspid aortic valves, which contradicts the current guidelines that excludes them from prophylaxis. Surgical treatment is often required and mortality remains substantial. Prevention of this serious complication should be one of the major tasks in the care of adults with CHD.

Congenital coronary collateral.

Intercoronary communications are a very rare congenital coronary artery anomalies. We report a case of a man who underwent elective coronary angiography that showed a bidirectional direct intercoronary communication between right coronary and left circumflex arteries.

Relationship of left ventricular global longitudinal strain with cardiac autonomic denervation as assessed by 123I-mIBG scintigraphy in patients with heart failure with reduced ejection fraction submitted to cardiac resynchronization therapy : Assessment of cardiac autonomic denervation by GLS in patients with heart failure with reduced ejection fraction submitted to CRT.

BACKGROUND: Heart failure (HF) is associated with cardiac autonomic denervation (AD), which can be non-invasively assessed by 123I-metaiodobenzylguanidine (123I-mIBG) scintigraphy and has prognostic implications. We aimed to study the relationship between myocardial contractility assessed by global longitudinal strain (GLS) and AD assessed by 123I-mIBG scintigraphy in advanced HF. METHODS/RESULTS: BETTER-HF is a prospective randomized clinical trial including HF patients (pts) submitted to cardiac resynchronization therapy (CRT) who are submitted to a clinical, echocardiographic, and scintigraphic assessment before and 6 months after CRT. 81 pts were included. An echocardiographic response (absolute increase in left ventricular ejection fraction ≥ 10%) was observed in 73.7% of pts. A higher baseline late heart-to-mediastinum ratio (HMR) was associated with a better echocardiographic response. There was a significant association between late HMR and GLS at baseline and 6 months. At baseline, GLS had an AUC of 0.715 for discrimination for a late HMR < 1.6. A GLS cut-off of - 9% maximized the likelihood of correctly classifying a pt as having severe AD (HMR < 1.6). CONCLUSION: Myocardial contractility as assessed by GLS is moderately correlated with AD as assessed by 123I-mIBG scintigraphy and has a good discrimination for the identification of severe cardiac denervation. GLS may allow for a more readily accessible estimation of the degree of AD in advanced HF pts.

Prognostic power of anaerobic threshold parameters in patients with transposition of the great arteries and systemic right ventricle.

INTRODUCTION: Both transposition of the great arteries (TGA) previously submitted to a Senning/Mustard procedure and congenitally corrected TGA (cc-TGA) have the systemic circulation supported by the morphological right ventricle, thereby rendering these patients to heart failure events risk. The aim of this study was to evaluate cardiopulmonary exercise test parameters for stratifying the risk of heart failure events in TGA patients. METHODS: Retrospective evaluation of adult TGA patients with systemic circulation supported by the morphological right ventricle submitted to cardiopulmonary exercise test in a tertiary centre. Patients were followed up for at least 1 year for the primary endpoint of cardiac death or heart failure hospitalisation. Several cardiopulmonary exercise test parameters were analysed as potential predictors of the combined endpoint and their predictive power were compared (area under the curve). RESULTS: Cardiopulmonary exercise test was performed in 44 TGA patients (8 cc-TGA), with a mean age of 35.1 ± 8.4 years. The primary endpoint was reached by 10 (22.7%) patients, with a mean follow-up of 36.7 ± 26.8 months. Heart rate at anaerobic threshold had the highest area under the curve value (0.864), followed by peak oxygen consumption (pVO2) (0.838). Heart rate at anaerobic threshold ≤95 bpm and pVO2 ≤20 ml/kg/min had a sensitivity of 87.5 and 80.0% and a specificity of 82.4 and 76.5%, respectively, for the primary outcome. CONCLUSION: Heart rate at anaerobic threshold ≤95 bpm had the highest predictive power of all cardiopulmonary exercise test parameters analysed for heart failure events in TGA patients with systemic circulation supported by the morphological right ventricle.

Bicuspid aortic valve outcomes.

BACKGROUND: Bicuspid aortic valve is the most common CHD. Its association with early valvular dysfunction, endocarditis, thoracic aorta dilatation, and aortic dissection is well established. OBJECTIVE: The aim of this study was to assess the incidence and predictors of cardiac events in adults with bicuspid aortic valve. METHODS: We carried out a retrospective analysis of cardiac outcomes in ambulatory adults with bicuspid aortic valve followed-up in a tertiary hospital centre. Outcomes were defined as follows: interventional - intervention on the aortic valve or thoracic aorta; medical - death, aortic dissection, aortic valve endocarditis, congestive heart failure, arrhythmias, or ischaemic heart disease requiring hospital admission; and a composite end point of both. Kaplan-Meier curves were generated to determine event rates, and predictors of cardiac events were determined by multivariate analysis. RESULTS: A total of 227 patients were followed-up over 13±9 years; 29% of patients developed severe aortic valve dysfunction and 12.3% reached ascending thoracic aorta dimensions above 45 mm. At least one cardiac outcome occurred in 38.8% of patients, with an incidence rate at 20 years of follow-up of 47±4%; 33% of patients were submitted to an aortic valve or thoracic aorta intervention. Survival 20 years after diagnosis was 94±2%. Independent predictors of the composite end point were baseline moderate-severe aortic valve dysfunction (hazard ratio, 3.19; 95% confidence interval, 1.35-7.54; p<0.01) and aortic valve leaflets calcification (hazard ratio, 4.72; 95% confidence interval, 1.91-11.64; p<0.005). CONCLUSIONS: In this study of bicuspid aortic valve, the long-term survival was excellent but with occurrence of frequent cardiovascular events. Baseline aortic valve calcification and dysfunction were the only independent predictors of events.

Giant pericardial cyst mimicking dextrocardia on chest X-ray.

Pericardial cysts are rare benign congenital malformations, usually small, asymptomatic and detected incidentally on chest X-ray as a mass located in the right costophrenic angle. Giant pericardial cysts are very uncommon and produce symptoms by compressing adjacent structures. In this report, the authors present a case of a symptomatic giant pericardial cyst incorrectly diagnosed as dextrocardia on chest X-ray.

Validation of a Heart Failure Risk Score in a Cohort of Cardiac Resynchronization Therapy Patients Under Remote Monitoring: Results from the TriageHF™ Algorithm.

The heart failure risk status (HFRS) is a validated dynamic tool for risk score prediction, based on the TriageHF™ algorithm (Medtronic, Minneapolis, MN, USA), for the occurrence of a heart failure (HF) event in the 30 days following a remote monitoring (RM) transmission. The aim of this study was to evaluate the accuracy of the HFRS in predicting an unplanned hospital admission due to HF decompensation in a real-world cohort of patients submitted to cardiac resynchronization therapy (CRT). We conducted a single-center review of a cohort of 40 consecutive HF patients, under RM, with CRT devices using the HFRS of the TriageHF™ algorithm. The correlation of the HFRS with hospital admissions was analyzed. During a mean follow-up of 36 months, a stepwise increase in the HFRS was significantly associated with a higher risk of HF admission (odds ratio, 12.7; 95% confidence interval, 3.2-51.5; P < .001), and the HFRS was demonstrated to have good discrimination for HF hospitalization, with an area under the receiver-operating characteristic curve of 0.812. The TriageHF™ algorithm effectively predicted HF-related hospitalization in a cohort of CRT patients during long-term RM follow-up, providing a novel clinical pathway to optimize the clinical management of this complex population.

Long term follow-up of Marfan Syndrome - experience of an adult congenital heart disease centre.

BACKGROUND: Marfan Syndrome (MFS) is one of the most common connective tissue disorders. The aim of this study was to characterize an adult population with MFS and evaluate its long-term prognosis. METHODS: A retrospective analysis of adult patients with MFS followed up during the past 40 years in a tertiary congenital heart disease outpatient clinic was performed. Survival analysis was performed according to different parameters, and survival curves were compared using the log-rank test. RESULTS: A total of 62 MFS patients were followed up for a mean period of 12 years (47% male; mean age, 39 years). The baseline mean aortic root diameter (ARD) at the Valsalva sinus was 42.4 ± 10.3 mm, with 15% of patients having moderate-to-severe aortic regurgitation and seven patients with acute aortic syndrome. The Bentall procedure was the most commonly performed surgical technique, and five patients required re-operation. Of the 17 pregnancies, 29% developed fetal complications; however, there was no maternal morbidity or mortality. A total of ten deaths occurred at a mean age of 52 years. Patients with an ARD ≤ 45 mm had a significantly lower all-cause mortality rate than patients with 45 < ARD ≤ 50 mm or with ARD > 50 mm (P = 0.004 and P < 0.001, respectively). Heart failure symptoms were associated with a worse outcome (P = 0.041), while the presence of extracardiac involvement had a protective effect (P < 0.001). CONCLUSION: MFS-related aortopathy is associated with high morbidity rates. In the overall population, an ARD > 45 mm at the time of diagnosis was associated with higher mortality during follow-up.

Paravalvular leak closure: Still a challenge with unpredictable results.

INTRODUCTION: Paravalvular leak (PVL) is a common serious complication associated with prosthetic valve implantation. OBJECTIVE: The aim of this study was to report our single-center experience in a retrospective review and to analyze possible predictors of success. METHODS: We performed 33 percutaneous PVL closures in 26 patients (54% female, mean age 65±13 years). All mitral prostheses were studied previously with 3D transesophageal echocardiography (TEE), and aortic prostheses with 2D/3D TEE. 3D TEE and fluoroscopy were used for the assessment, planning, and guidance of the interventions. Twelve patients also underwent computed tomography angiography for better characterization of anatomic details. RESULTS: Eighteen patients (69.2%) were admitted due to heart failure (New York Heart Association [NYHA] III or IV, seven (26.9%) because of heart failure and hemolysis, and one (3.8%) due to hemolysis only. Regarding the leaks, 46.2% were in aortic and 53.8% in mitral prostheses, 88.5% in mechanical and 7.7% in biological prostheses, and 3.8% in transcatheter aortic valve implants. All the aortic patients had severe aortic regurgitation. Furthermore, all mitral patients but one had moderate to severe or severe mitral regurgitation. Closure was successful in 17 patients (65.4%), partially successful in four (15.4%) and unsuccessful in five (19.2%). After the procedure, 69% were in NYHA I-II. Hemolysis worsened in three patients despite successful closure; all required further valvular surgery and two died. Regarding angiographic and echocardiographic procedural success, we analyzed age, gender, type of prosthesis (mechanical or biological), location (aortic or mitral), clinical data, maximum leak diameter, anatomic regurgitant orifice, leak location (anterior, posterior, inferior and lateral for mitral leaks and left, right and non-coronary sinus for aortic leaks), and number of devices (plugs) used for closure. No parameters presented a significant relationship with success excepting previous hemolysis. There was a relationship between clinical improvement and reduction of PVL (p=0.0001). In follow-up, cardiac-related events (new hospital admissions, cardiac valvular surgery, need for transfusion) were more frequent in patients with partially successful or unsuccessful closure (p=0.012). There was a relationship between cardiac-related events and death (p=0.029). CONCLUSION: Percutaneous PVL closure has emerged as an alternative treatment for PVL. Predictors of procedural success are difficult to establish. Survival is related to reduction of regurgitation and improvement in NYHA functional class.

Impact of substrate-based ablation for ventricular tachycardia in patients with frequent appropriate implantable cardioverter-defibrillator therapy and dilated cardiomyopathy: Long-term experience with high-density mapping.

INTRODUCTION: Recurrent ventricular tachycardia (VT) episodes have a negative impact on the clinical outcome of implantable cardioverter-defibrillator (ICD) patients. Modification of the arrhythmogenic substrate has been used as a promising approach for treating recurrent VTs. However, there are limited data on long-term follow-up. AIM: To analyze long-term results of VT substrate-based ablation using high-density mapping in patients with severe left ventricular (LV) dysfunction and recurrent appropriate ICD therapy. METHODS: We analyzed 20 patients (15 men, 55% with non-ischemic cardiomyopathy, age 58±15 years, LV ejection fraction 32±5%) and repeated appropriate shocks or arrhythmic storm (>2 shocks/24 h) despite antiarrhythmic drug therapy and optimal heart failure medication. All patients underwent ventricular programmed stimulation (600 ms/S3) to document VT. A sinus rhythm (SR) voltage map was created with a three-dimensional electroanatomic mapping system (CARTO, Biosense Webster, CA) using a PentaRay® high-density mapping catheter (Biosense Webster, CA) to delineate areas of scarred myocardium (ventricular bipolar voltage ≤0.5 mV - dense scar; 0.5-1.5 mV - border zone; ≥1.5 mV - healthy tissue) and to provide high-resolution electrophysiological mapping. Substrate modification included elimination of local abnormal ventricular activities (LAVAs) during SR (fractionated, split, low-amplitude/long-lasting, late potentials, pre-systolic), and linear ablation to obtain scar homogenization and dechanneling. Pace-mapping techniques were used when capture was possible. The LV approach was retrograde in nine cases, transseptal in five and epi-endocardial in four. In two patients ablation was performed inside the right ventricle. RESULTS: LAVAs and scar areas were modified in all patients. Mean procedure duration was 149 min (105-220 min), with radiofrequency ranging from 18 to 70 min (mean 33 min) and mean fluoroscopy time of 15 min. Non-inducibility was achieved in 75% of cases (in four patients with hemodynamic deterioration and an LV assist device, VT inducibility was not performed). There were two cases of pericardial tamponade, drained successfully. During a follow-up of 50±24 months, 65% had no VT recurrences. Among the seven patients with recurrences, three underwent redo ablation and four, with fewer VT episodes, received appropriate ICD therapy. There were five hospital readmissions due to heart failure decompensation, one patient died in the first week after unsuccessful ablation of a VT storm and three died (stroke and pneumonia) >1 year after ablation. CONCLUSION: Catheter ablation based on substrate modification is feasible and safe in patients with frequent VTs and severe LV dysfunction. This approach may be of clinical relevance, with potential long-term benefits in reducing VT burden.

Prevalence and prognostic impact of apical sparing contractility pattern in patients with aortic stenosis referred for transcatheter aortic valve implantation.

INTRODUCTION: Prolonged afterload increase in aortic stenosis (AS) may alter left ventricular (LV) contractility, irrespective of LV ejection fraction (LVEF). The prevalence and morbimortality associated with the apical sparing strain pattern (ASP), a typical finding of cardiac amyloidosis (CA), are not fully understood in patients with AS. We assessed the prevalence of the ASP in patients with severe AS and its clinical impact after transcatheter aortic valve implantation (TAVI). METHODS: Eighty-nine consecutive patients with severe AS and LV hypertrophy referred for TAVI were included. Baseline clinical and echocardiographic data were assessed, including the ASP in bull's eye plots (ASPB), relative apical longitudinal strain (RALS) and EF to global longitudinal strain (EF/GLS) ratio. We analysed all-cause mortality; a composite of all-cause mortality, stroke, and heart failure hospitalizations; and the rate of pacemaker implantation, after TAVI. RESULTS: Mean age was 82 ± 6 years and mean LVEF was 57 ± 10%. ASPB and RALS >1 were present in 43.8% and 24.7% of patients, respectively. Over a median follow-up of 13 months (IQR 6-32), ASPB was associated with higher rates of all-cause mortality (log-rank P=0.001) and was an independent predictor of all-cause mortality in multivariate analysis. Combination of the ASPB and GLS or EF/GLS ratio improved the risk stratification. Patients with RALS >1 were more likely to have new BBB and an indication for pacemaker implantation (P=0.048). CONCLUSION: The ASP, as assessed by the ASPB and RALS, was frequent in patients with AS regardless of the diagnosis of CA. The ASPB may refine risk stratification in patients referred for TAVI.

Nocardial endocarditis after mitral valve replacement: case report and review of the literature.

Nocardia causes several types of infection in both immunocompetent and immunocompromised hosts, and may affect any organ. Endocarditis due to infection by Nocardia species is rare and has a poor prognosis. To our knowledge, after a literature review, only 12 cases of nocardial endocarditis have been reported, most treated with valve replacement. We report the case of a patient with prosthetic valve endocarditis due to Nocardia species, who was successfully treated with antimicrobial chemotherapy only (trimethoprim-sulfamethoxazole), instead of valve replacement.

Myocardial work improvement after sacubitril-valsartan therapy: a new echocardiographic parameter for a new treatment.

AIMS: Myocardial work is a new transthoracic echocardiogram (TTE) parameter that enhances the information provided through left ventricular (LV) global longitudinal strain (GLS). Nothing is known about the impact of sacubitril/valsartan (LCZ696) therapy on myocardial work parameters. The aim of this study was to evaluate the effects of LCZ696 on LV myocardial work in heart failure patients. METHODS: Prospective evaluation of chronic heart failure patients with LV ejection fraction of 40% or less despite optimized standard of care therapy, in which LCZ696 therapy was started and no other heart failure treatment was expected to change. TTE study was performed before and 6 months after LCZ696 therapy. A semiautomated analysis of LV GLS was made and myocardial work estimated using custom software of the GE Vivid E95 ultrasound system. RESULTS: Of the 42 patients, 35 (83.3%) completed the 6 months, follow-up, since 2 (4.8%) patients died and 5 (11.9%) discontinued treatment due to adverse events. Mean age was 58.6 ±â€Š11.1 years. TTE data showed a significant reduction in LV dimensions and atrial volumes, as well as an improvement in LV ejection fraction (29.3 vs. 35.2%, P = 0.001) and GLS (-7.0 vs. -8.9%, P = 0.001). Myocardial work had a significant increase in global constructive work (720.2 vs. 900.6 mmHg%, P = 0.016) and global work efficiency (78.6 vs. 86.6%, P = 0.027), with a nonsignificant decrease in global wasted work (150.2 vs. 136.8 mmHg%, P = 0.441) at 6 months. CONCLUSION: LCZ696 therapy was associated with signs of reverse remodelling by usual TTE parameters and LV myocardial work at 6 months, including an increase in global constructive work and work efficiency.

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

BACKGROUND: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. METHODS: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. RESULTS: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). CONCLUSIONS: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

Giant septal cavity due to coronary artery fistula and ventricular septal dissection after cardiac surgery.

Ventricular septal dissection may rarely result from infective endocarditis, myocardial infarction or sinus of Valsalva aneurysm progression. A rare case that developed in a 66-year-old female after mitral valve replacement for severe mitral regurgitation with cordal rupture is presented and discussed. It resulted from a coronary artery fistula, from a septal branch, to a 6 cm wide saccular cystic cavity within the interventricular septum, which was detected by transthoracic echocardiography some months after surgery. Coronary arteries were anatomically normal. Coronary angiography was helpful to clarify the origin of the fistula. Later on the patient developed heart failure and atrial fibrillation, but she refused any further intervention. She has been followed up for more than 7 years and is presently stable on medical therapy. A review of the peculiar aspects of the case is done and the most relevant aspects and images are presented and discussed.

Primary undifferentiated sarcoma of the mitral and aortic valves.

Although sarcomas are the most frequent primary malignant tumor of the heart, they very rarely involve only the left heart valves. A 72-year-old woman was diagnosed with a severe mitral valve disease and referred for cardiac surgery. Preoperative transthoracic echocardiography revealed a cardiac mass involving the mitral and aortic valves. The aortic valve had an unusual appearance, with a cystic mass protruding to the left ventricular outflow tract. The mitral valve apparatus was also involved, with chordal rupture. Extended resection and dual valve replacement was performed. A histological examination revealed an undifferentiated sarcoma. Postoperatively, neither chemotherapy nor radiotherapy therapy was used. Although most patients may benefit from adjunctive therapy, some respond well in the short term with only surgical resection, despite the poor prognosis of this rare entity.

Longitudinal strain by two-dimensional speckle tracking to assess ventricular function in adults with transposition of the great arteries: Can serial assessment be simplified?

INTRODUCTION: Transposition of the great arteries (TGA) is a rare form of congenital heart disease in which most patients reach adulthood. Right ventricular dysfunction is the most severe residual complication in long-term follow-up, both in patients treated by atrial switch and in those with congenitally corrected TGA. New echocardiographic tools such as longitudinal strain by two-dimensional (2D) speckle tracking may improve assessment of ventricular function in these patients. METHODS AND RESULTS: We performed a retrospective analysis of echocardiograms in adult patients with TGA (26 patients with dextro-TGA - 15 treated by atrial switch and six by arterial switch - and five with congenitally corrected TGA) and in a control group of 14 healthy individuals. Right ventricular strain was significantly worse (p<0.001), as was the corresponding annular plane systolic excursion (p=0.010) in atrial switch patients, in comparison to arterial switch patients, while no differences were found in left ventricular parameters. In the overall population, systemic right ventricular parameters were significantly less negative than pulmonary right ventricular parameters, and these were less negative than in controls. Left ventricular parameters were similar across groups, except for pulmonary left ventricular strain, which was worse than in controls (p=0.008) as well as pulmonary right ventricular strain. CONCLUSIONS: Assessment of ventricular function in patients with TGA by 2D speckle tracking longitudinal strain is easy and feasible and may be a useful tool for serial follow-up. Of particular note, we found that there is also some degree of ventricular dysfunction even after re-establishment of normal connections.

Impact on long-term cardiovascular outcomes of different cardiac resynchronization therapy response criteria.

INTRODUCTION: There is a lack of consensus on the definition of response to cardiac resynchronization therapy (CRT), and it is not clear which response criteria have most influence on cardiac event-free survival. OBJECTIVES: To assess the predictive value of various response criteria in patients undergoing CRT and the agreement between them. METHODS: We performed a secondary analysis of the BETTER-HF trial. Patient response was classified at six months after CRT according to eleven criteria used in previous trials. The predictive value of response criteria for survival free from mortality, cardiac transplantation and heart failure hospitalization was assessed by Cox regression analysis. Agreement between the different response criteria was assessed using Cohen's kappa (κ). RESULTS: A total of 115 patients were followed for a mean of 25 months. During follow-up, 15 deaths occurred (13%) and 29 patients had at least one adverse cardiac event (25%). Only five of the eleven response criteria were predictors of event-free survival. The most powerful isolated clinical and echocardiographic predictors were a reduction of ≥1 NYHA functional class (HR 0.39 for responders; 95% CI 0.18-0.83, p=0.014) and an increase of at least 15% in left ventricular ejection fraction (HR 0.43, 95% CI 0.20-0.90, p=0.024), respectively. Agreement between the different response criteria was poor. CONCLUSIONS: Most currently used response criteria do not predict clinical outcomes and have poor agreement. It is essential to establish a consensus on the definition of CRT response in order to standardize studies.

Overview on Inhalable Nanocarriers for Respiratory Immunization.

Despite the value of vaccination, the control of re-emerging infectious and non-infectious diseases remains a challenge for researchers. In this topic, mucosal immunization, in particular at airway mucosa, is receiving increased investigational focus. Innovative vaccine platforms to deliver immunogens with or without adjuvants in a safe and stable manner have been explored to improve vaccine efficacy and induce long-term and protective immunity. This review provides an overview of the features of respiratory immunization and the fate of inhalable nanocarriers in the respiratory tract. The review also highlights the most representative delivery approaches based on inhalable nanocarriers, including polymeric, lipid and inorganic-based nanosystems, which can enhance vaccine uptake by antigen-presenting cells. The review takes into consideration the most relevant and recent in vivo studies to provide readers a realistic insight into the potential of these technologies in the advantages and potential hurdles to clinical and commercial success of these platforms for vaccination.