Therapeutic approach in heart failure with poor diuretic response: peripheral ultrafiltration vs. conventional treatment.

AIMS: Patients with heart failure (HF) admitted for decompensation often require high doses of intravenous diuretics. This study aims to analyse whether the use of peripheral ultrafiltration (UF) in patients hospitalized for acute HF with systemic-predominant congestion results in better hydric control, renal protection, and reduction of hospital stay compared with conventional treatment. METHODS AND RESULTS: This study was a retrospective, comparative, single-centre study of 56 patients admitted for HF with systemic congestion with a poor diuretic response after diuretic escalation. One group underwent peripheral UF (35 patients) and others were maintained on intense diuretic treatment (control group, 21 patients). The diuretic response and days of hospital stay were compared between and within groups. The baseline characteristics of both groups were similar: males with right ventricular failure and renal dysfunction. The inter-group analysis showed that patients who received UF had better glomerular filtration rate (GFR; UF: 39.2 ± 18.2 vs. control: 28.7 ± 13.4 mL/min; P = 0.031) and higher diuresis (UF: 2184 ± 735 vs. control: 1335 ± 297 mL; P = 0.0001) at hospital discharge despite less need for diuretic drugs. Days of hospital stay were shorter in the UF group (UF: 11.7 ± 10.1 vs. control: 19.1 ± 14.4 days; P = 0.027). Intra-group analysis showed that patients receiving UF improved GFR, increased diuresis, and reduced weight at discharge (P < 0.001), whereas patients on conventional treatment only experienced improved weight but worsening renal function at discharge. CONCLUSIONS: In patients with acute HF with systemic congestion and diuretic resistance, UF compared with conventional treatment produces greater decongestion and renal protection, reduces the total diuretic load, and shortens the length of hospital stay.

Is the Benefit of Treating Iron Deficiency Greater in Acute Heart Failure with Renal Dysfunction?

BACKGROUND: This study aims to analyse whether in acute heart failure (AHF) with iron deficiency (ID), the administration of ferric carboxymaltose (FCM) produces a greater benefit in renal dysfunction. METHODS: A total of 812 consecutive patients admitted for AHF and ID were studied. Untreated (n:272) and treated (n:540) patients were compared. The six-month prevalence of a combined event (readmission for HF, all-cause death, and emergency department visit for decompensation) was analysed. Three grades of renal dysfunction (KDIGO) were compared, Group 1 (grades 1 and 2), Group 2 (grades 3a and 3b), and Group 3 (grades 4 and 5). RESULTS: There were differences in sex distribution (untreated group: males 39.7% vs. treated group: males 51.9%; p < 0.001). Sex-adjusted combined event analysis showed a greater benefit in Group 1 (OR: 0.31, 95% CI:0.19-0.5; p < 0.001) and Group 2 (OR: 0.23, 95% CI:0.14-0.38; p < 0.001), but not in Group 3 (OR: 0.51, 95% CI:0.17-0.55; p: 0.237). CONCLUSIONS: The administration of FCM in patients with AHF and ID reduces the combined event analysed. The benefit is greater when renal dysfunction is present, except in very advanced degrees where no significant benefit is obtained.

Evolving Indications for Heart-Lung Transplant in Spain.

BACKGROUND: The outcomes of heart-lung transplant (HLT) are worse than those of heart transplant (HT) and lung transplant alone; this and the availability of mechanical assistance have meant that the indications for HLT have been changing. This study aims to analyze the evolution of indications for HLT in a country of 47 million inhabitants. METHODS: We performed a retrospective observational study of all HLTs performed in Spain (performed in 2 centers) from 1990 to 2020. The total number of patients included was 1751 (HT 1673 and HLT 78). After clinical adjustment, overall survival was compared between the 2 groups. Seven etiological subgroups were considered within the HLT group: (1) cardiomyopathy with pulmonary hypertension (CM + PH);, (2) Eisenmenger syndrome, (3) congenital heart disease without Eisenmenger syndrome, (4) idiopathic pulmonary arterial hypertension (IPAH), (5) cystic fibrosis, (6) chronic obstructive pulmonary disease (COPD) and/or emphysema), and (7) diffuse interstitial lung disease. RESULTS: There were a large number of differences between patients with HLT vs HT. HLT had a 2.69-fold increased probability of death in the first year compared with HT. The indications for HLT have changed over the years. In the recent period the indications are mainly congenital heart disease and Eisenmenger syndrome, with some cases of CM + PH. Other indications for HLT have virtually disappeared, mainly lung diseases (IPAH, COPD, cystic fibrosis). Median survival was low in CM + PH (18 days), diffuse interstitial lung disease (29 days), and ischemic heart disease (114 days); intermediate in Eisenmenger syndrome (600 days); and longer in IPAH, COPD and/or emphysema, and cystic fibrosis. CONCLUSIONS: HLT is a procedure with high mortality. This and mechanical assists mean that the indications have changed over the years. Etiological analysis is of utmost interest to take advantage of organs and improve survival.

Prevalence of Tricuspid Regurgitation After Orthotopic Heart Transplantation and Its Evolution in the Follow-up Period: A Long-Term Study.

BACKGROUND: Tricuspid regurgitation (TR) after heart transplant (HT) can be an important complication depending on its etiology and severity. This study aims to analyze the prevalence of TR, the causes, and its evolution over time after HT. METHODS: We performed a retrospective study of transplants performed between 2000 and 2019 in 2 centers (1009 patients). TR was grouped according to etiology: primary graft dysfunction (PGD), acute rejection, cardiac allograft vasculopathy (CAV), pulmonary hypertension, prolapse, endomyocardial biopsy complication (EMB), pacemaker (PM), and unclear etiology (TR not related to any process and for which no justification was found). RESULTS: The prevalence of TR after HT was 19.8% (moderate: 13.2%, severe: 6.6%). Significant TR was more prevalent in the first months (month 1: 51%, month 3: 40%, month 6: 29%, 1 year: 24%). These results were related to the etiologies. Thus, in the first month, TR due to PGD is frequent and it is the only time when TR due to pulmonary hypertension appears. During the first 6 months, TR of unclear cause gains relevance, which tends to decrease over time. After 1 year, TR due to rejection predominates. After 5 years, TR is less frequent (< 10%) and related to long-term complications of HT, such as CAV, EMB, and those associated with PM. CONCLUSIONS: The prevalence of TR after HT is 19.8%. Prevalence and etiology change over time. Initially it is usually related to PGD, in the medium-term to rejection and in the long-term to CAV and procedures such as EMB and PM.

Why Iron Deficiency in Acute Heart Failure Should Be Treated: A Real-World Clinical Practice Study.

Background. This study aims to determine whether the administration of ferric carboxymaltose (FCM) in patients with acute heart failure (AHF) and iron deficiency (ID) improves morbidity and mortality. Methods. We studied 890 consecutive patients admitted for AHF. Patients were divided into six groups according to reduced left ventricular ejection fraction (HFrEF) or preserved (HFpEF), presence of ID, and administration of FCM. Emergency visits, re-admissions, and all-cause mortality were assessed at 6 months. Results. The overall prevalence of ID was 91.2%. In the HFrEF group, no differences were found in isolated events when patients with untreated vs. treated ID were compared, while differences were found in the combined event rate (p = 0.049). The risk calculation showed an absolute risk reduction (ARR) of 10% and relative risk reduction (RRR) of 18%. In HFpEF there was a positive trend with regard to the combined event (p = 0.107), with an ARR of 9% and an RRR of 15%. The number of patients we needed to treat to prevent a combined event was 10.5 in HFrEF and 10.8 in HFpEF. Conclusions. FCM in AHF reduced the combined event rate of emergency visits, re-admission, and all-cause death at 6 months in HF with left ventricular ejection fraction <50%, and showed a positive trend in HFpEF.

MicroRNA-4732-3p Is Dysregulated in Breast Cancer Patients with Cardiotoxicity, and Its Therapeutic Delivery Protects the Heart from Doxorubicin-Induced Oxidative Stress in Rats.

Anthracycline-induced cardiotoxicity is the most severe collateral effect of chemotherapy originated by an excess of oxidative stress in cardiomyocytes that leads to cardiac dysfunction. We assessed clinical data from patients with breast cancer receiving anthracyclines and searched for discriminating microRNAs between patients that developed cardiotoxicity (cases) and those that did not (controls), using RNA sequencing and regression analysis. Serum levels of 25 microRNAs were differentially expressed in cases versus controls within the first year after anthracycline treatment, as assessed by three different regression models (elastic net, Robinson and Smyth exact negative binomial test and random forest). MiR-4732-3p was the only microRNA identified in all regression models and was downregulated in patients that experienced cardiotoxicity. MiR-4732-3p was also present in neonatal rat cardiomyocytes and cardiac fibroblasts and was modulated by anthracycline treatment. A miR-4732-3p mimic was cardioprotective in cardiac and fibroblast cultures, following doxorubicin challenge, in terms of cell viability and ROS levels. Notably, administration of the miR-4732-3p mimic in doxorubicin-treated rats preserved cardiac function, normalized weight loss, induced angiogenesis, and decreased apoptosis, interstitial fibrosis and cardiac myofibroblasts. At the molecular level, miR-4732-3p regulated genes of TGFß and Hippo signaling pathways. Overall, the results indicate that miR-4732-3p is a novel biomarker of cardiotoxicity that has therapeutic potential against anthracycline-induced heart damage.

Cardiac Allograft Rejection Induces Changes in Nucleocytoplasmic Transport: RANGAP1 as a Potential Non-Invasive Biomarker.

The non-invasive diagnosis of acute cellular rejection (ACR) is a major challenge. We performed a molecular study analyzing the predictive capacity of serum RanGTPase AP1 (RANGAP1) for diagnosing ACR during the first year after heart transplantation (HT). We included the serum samples of 75 consecutive HT patients, extracted after clinical stability, to determine the RANGAP1 levels through ELISA. In addition, various clinical, analytical, and echocardiographic variables, as well as endomyocardial biopsy results, were collected. RANGAP1 levels were higher in patients who developed ACR (median 63.15 ng/mL; (inter-quartile range (IQR), 36.61-105.69) vs. 35.33 ng/mL (IQR, 19.18-64.59); p = 0.02). Receiver operating characteristic (ROC) curve analysis confirmed that RANGAP1 differentiated between patients with and without ACR (area under curve (AUC), 0.70; p = 0.02), and a RANGAP1 level exceeding the cut-off point (≥90 ng/mL) was identified as a risk factor for the development of ACR (OR, 6.8; p = 0.006). Two independent predictors of ACR identified in this study were higher RANGAP1 and N-terminal pro-brain natriuretic peptide levels. The analysis of the ROC curve of the model showed a significant AUC of 0.77, p = 0.001. Our findings suggest that RANGAP1 quantification facilitates risk prediction for the occurrence of ACR and could be considered as a novel non-invasive biomarker of ACR.

Cardiovascular Events During and After Bronchiectasis Exacerbations and Long-term Mortality.

BACKGROUND: Population-based and retrospective studies have shown that risk for cardiovascular events such as arrythmias, ischemic episodes, or heart failure, increase during and after bronchiectasis exacerbations. RESEARCH QUESTION: What are the risk factors for cardiovascular events (CVE) during and after bronchiectasis exacerbations and their impact on mortality? STUDY DESIGN AND METHODS: This was a post hoc retrospective analysis of a prospective observational study of 250 patients with bronchiectasis at two tertiary care hospitals. Only the first exacerbation was considered for each patient, collecting demographic, comorbidity, and severity data. The main outcomes were the appearance of CVE and mortality. Risk factors for CVE were analyzed using a semi-competing risks model. RESULTS: During a median follow-up of 35 months, 74 (29.6%) patients had a CVE and 93 (37.2%) died. Semi-competing risk analysis indicated that age, arterial hypertension, COPD, and potentially severe exacerbations significantly increased the risk for developing CVE. Compared with patients without CVE, those with CVE had higher mortality. INTERPRETATION: Demographic factors and comorbidities are risk factors for the development of CVE after an acute exacerbation of bronchiectasis. The appearance of CVE worsens long-term prognosis.

Diagnostic value of serum miR-144-3p for the detection of acute cellular rejection in heart transplant patients.

BACKGROUND: The development of noninvasive approaches for the early diagnosis of acute cellular rejection (ACR), an important complication of cardiac transplantation, is of great importance in clinical practice. We conducted a nontargeted transcriptomic study focused on identifying serum miRNAs to evaluate their diagnostic accuracy for detecting rejection episodes. METHODS: We included consecutive serum samples from transplant recipients undergoing routine endomyocardial biopsies. In the discovery phase (n = 40), an RNA sequencing analysis (Illumina HiSeq 2500 sequencer) was performed. We focused on the validation of miR-144-3p in a larger patient cohort (n = 212), selected based on the criteria of higher accuracy for ACR detection. ACR was assessed according to the International Society for Heart and Lung Transplantation. RESULTS: In the discovery phase, 26 altered miRNAs were identified as potential markers for detecting ACR. miR-144-3p showed the best results, it was the only molecule with an AUC greater than 0.95 to detect Grade ≥2R ACR and it showed significant differences in its levels when we compared Grade 1R ACR with the nonrejection group. In the validation phase, we confirmed this finding, and it had an excellent diagnostic capacity for clinically relevant rejection (Grade ≥2R AUC = 0.801, p < 0.0001), detecting mild rejection (Grade 1R AUC = 0.631, p < 0.01) and was an independent predictor for the presence of ACR (odds ratio of 14.538, p < 0.01). CONCLUSIONS: ACR is associated with the differential expression of specific serum miRNAs that correlate with the severity of the episode. Circulating miR-144-3p is a candidate noninvasive ACR biomarker that could contribute to improving the surveillance of cardiac transplanted patients.

Creatinine and NT-ProBNP levels could predict the length of hospital stay of patients with decompensated heart failure.

BACKGROUND: Heart failure (HF) is a clinical syndrome that causes high morbidity and mortality with a high number of admissions and sometimes prolonged admissions. This study aimed at assessing whether parameters detected during the first 24 h of admission may predict a prolonged hospital stay in patients admitted to hospital for decompensated HF. METHODS: From January 2016 to December 2019, 2359 admissions of decompensated HF were recorded. In-hospital transfers, de novo HF, deaths and scheduled admissions were discarded to homogenise the sample. Finally, 1196 patients were included. The sample was divided into two groups: (a) non-prolonged admission (n = 643, admission ≤7 days) or (b) prolonged admission (n = 553, admission >7 days). Clinical, analytical, electrocardiographic and echocardiographic variables obtained during the first 24 h of admission were analysed. RESULTS: Univariate differences were found at admission in NT-ProBNP, creatinine, history of cardiac surgery, smoking and alcoholism, left and right ventricular ejection fraction, systolic blood pressure and heart rate. The ROC analysis showed significant areas under the curve for the NT-ProBNP (AUC: 0.63, 95% CI: 0.60-0.67; p < 0.001) and creatinine (AUC: 0.69, 95% CI: 0.66-0.72; p < 0.0001). The variables associated with prolonged hospital admission were NT-ProBNP (OR: 1, 95% CI: 1-1; p < 0.001), creatinine (OR: 2.2, 95% CI: 1.8-2.7; p < 0.0001) and previous smoking (OR: 1.5, 95% CI: 0.4-1; p < 0.02). CONCLUSIONS: Variables such as creatinine and NT-ProBNP at hospital admission may define a subgroup of patients who will probably have a long hospital stay. Therefore, the planning of hospital care and transition to discharge may be enhanced.

Time course and predictors for neoaortic root dilatation and neoaortic valve regurgitation during adult life after arterial switch operation.

INTRODUCTION AND OBJECTIVES: There are limited data on the long-term development of neoaortic root dilatation (NRD) and neoaortic valve regurgitation (AR) after arterial switch operation (ASO) for transposition of the great arteries during adult life. METHODS: We performed a retrospective longitudinal analysis of 152 patients older than 15 years who underwent ASO for transposition of the great arteries and who were followed-up for 4.9±3.3 years in 2 referral centers. Sequential changes in body surface-adjusted aortic root dimensions and progression to moderate/severe AR were determined in patients with 2 or more echocardiographic examinations. Risk factors for dilatation were tested by Cox regression to identify predictors of AR progression. RESULTS: At baseline, moderate AR was present in 9 patients (5.9%) and severe AR in 4 (2.6%), of whom 3 had required aortic valve surgery. Initially, the median neoaortic root dimension was 20.05±2.4mm/m2, which increased significantly to 20.73±2.8mm/m2 (P <.001) at the end of follow-up. The mean change over time was 0.14mm/m2/y (95%CI, 0.07-0.2). Progressive AR was observed in 20 patients (13.5%) and 6 patients (4%) required aortic valve surgery. Progressive AR was associated with bicuspid valve, AR at baseline, NRD at baseline, and neoaortic root enlargement. Independent predictors were bicuspid valve (HR, 3.3; 95%CI, 1.1-15.2; P=.037), AR at baseline (HR, 5.9; 95%CI, 1.6-59.2; P=.006) and increase in NRD (HR, 4.1 95%CI, 2-13.5; P=.023). CONCLUSIONS: In adult life, NRD and AR progress over time after ASO. Predictors of progressive AR are bicuspid valve, AR at baseline, and increase in NRD.

Genotype FBN1/phenotype relationship in a cohort of patients with Marfan syndrome.

Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the fibrillin-1 (FBN1) gene, and cardiovascular involvement is the leading cause of mortality. We sought to examine the genotype/phenotype realtionship in 61 consecutive patients with a phenotype and genotype compatible with MFS. The FBN1 gene was analyzed by massive sequencing using a hybridization capture-based target enrichment custom panel. Forty-three different variants of FBN1 were identified, of which 17 have not been previously reported. The causal variants of MFS were grouped into mutations resulting in haploinsufficiency (HI group; 23 patients) and mutations producing a dominant-negative effect (DN group; 38 patients). Patient information was collected from electronic medical records and clinical evaluation. While no significant differences were found between the two groups, the HI group included more cases with aortic dissection and occurring at a younger age that the DN group (34.7% vs. 15.8%; p = 0.160). Irrespective of the mutation group, males presented with a higher probability of aortic involvement (4-fold higher risk than females) and aortic dissections events occurred at younger ages. Patients with DN variants carrying a cysteine substitution had a higher incidence of ectopia lentis.

Evaluation of a near-zero fluoroscopic approach for catheter ablation in patients with congenital heart disease.

PURPOSE: Radiation exposure (RE) is a matter of concern for patients with congenital heart disease (CHD) who not infrequently need multiple interventional procedures under fluoroscopy guidance. We sought to evaluate the safety and feasibility of a minimally fluoroscopic approach in patients with CHD undergoing catheter ablation using a new image integration module (IIM). METHODS: Consecutive patients with CHD undergoing catheter ablation using the Carto Univu™ IIM were included. A near-zero fluoroscopy procedure was defined by an effective dose (ED) ≤ 1 mSv. RE parameters (total fluoroscopy time [TFT], total dose area product [tDAP], and ED), ablation outcomes, and complications were evaluated. RESULTS: Fifty-five patients with CHD underwent 63 ablation procedures (supraventricular tachycardia, n = 53; ventricular tachycardia, n = 10). The CHD was simple in 25%, moderate in 42%, and complex in 33%. The use of the IIM resulted in very low levels of RE (median TFT 0.13 min [IQR 0-1.04], median tDAP 54.5 cGy cm2 [IQR 9.5-176.4], median ED 0.136 mSv [IQR 0.02-0.49]). Patients with complex CHD had significantly higher RE when compared with patients with simple and moderate defects. A total of 56/63 ablation procedures (89%) were performed with an ED ≤ 1 mSv. One patient developed sinus node dysfunction requiring pacemaker implantation. CONCLUSIONS: The use of a minimally fluoroscopic approach was safe and feasible resulting in very low RE during catheter ablation of patients with CHD. A near-zero fluoroscopy ablation was possible in up to 89% of the procedures.

Left ventricular myocardial dysfunction in arrhythmogenic cardiomyopathy with left ventricular involvement: A door to improving diagnosis.

BACKGROUND: Diagnostic Task Force Criteria (TFC) for arrhythmogenic cardiomyopathy (AC) exhibit poor performance for left dominant forms. TFC only include right ventricular (RV) dysfunction (akinesia, dyssynchrony, volumes and ejection fraction). Moreover, cardiac magnetic resonance imaging (CMRI) assessment of left ventricular (LV) dyssynchrony has hitherto not been described. Thus, we aimed to comprehensively characterize LV CMRI behavior in AC patients. METHODS: Thirty-five AC patients with LV involvement and twenty-three non-affected family members (controls) were enrolled. Feature-tracking analysis was applied to cine CMRI to assess LV ejection fraction (LVEF), LV end-systolic and end-diastolic volume indexes, strain values and dyssynchrony. Regions with more frequent strain and dyssynchrony impairment were also studied. RESULTS: Radial dyssynchrony and LVEF were selected (sensitivities 54.3% and 48.6%, respectively at 100% specificity), with a threshold of 70 ms for radial dyssynchrony and 48.5% for LVEF. 71.4% of patients exceeded these thresholds (31.4% both, 22.9% only dyssynchrony and 17.1% only LVEF). Considering these cut-off values as a novel combined criterion, 30% of patients with 'borderline' or 'possible' AC following 2010 TFC would move to a 'definite' AC diagnosis. Strain was globally impaired whereas dyssynchronous regions were more often apical and located at the inferolateral wall. CONCLUSIONS: Mirroring the RV evaluation, we suggest including LVEF and LV dyssynchrony to improve the diagnosis of AC. Two independent mechanisms can be claimed in AC patients with LV involvement: 1) decreased myocardial deformation with global LV affectation and 2) delayed myocardial contraction at localized regions.

SERCA2a: A potential non-invasive biomarker of cardiac allograft rejection.

BACKGROUND: The detection of heart transplant rejection by non-invasive methods remains a major challenge. Despite the well-known importance of the study of sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) in the heart, its role as a rejection marker has never been analyzed. Our objective in this study was to determine whether circulating SERCA2a could be a good marker of cardiac rejection. METHODS: We collected 127 consecutive endomyocardial biopsies (EMBs) and serum samples from adult heart transplant recipients (49 without allograft rejection and 78 with the diagnosis of biopsy allograft rejection, including 48 Grade 1R, 21 Grade 2R and 9 Grade 3R). Serum concentrations of SERCA2a were determined using a specific sandwich enzyme-linked immunosorbent assay. We also analyzed SERCA2a expression changes on EMBs using immunofluorescence. RESULTS: SERCA2a cardiac tissue and serum levels were decreased in patients with cardiac rejection (p < 0.0001). A receiver-operating characteristic analysis showed that SERCA2a strongly discriminated between patients with and without allograft rejection: normal grafts vs all rejecting grafts (AUC = 0.804); normal grafts vs Grade 1R (AUC = 0.751); normal grafts vs Grade 2R (AUC = 0.875); normal grafts vs Grade 3R (AUC = 0.922); normal grafts vs Grade 2R and 3R (AUC = 0.889), with p < 0.0001 for all comparisons. CONCLUSIONS: We demonstrated that changes in SERCA2a cardiac tissue and serum levels occur in cardiac allograft rejection. Our findings suggest that SERCA2a concentration assessment may be a relatively simple, non-invasive test for heart transplant rejection, showing a strong capability for detection that improves progressively as rejection grades increase.

Safety and Feasibility of a Minimally Fluoroscopic Approach for Ventricular Tachycardia Ablation in Patients With Structural Heart Disease: Influence of the Ventricular Tachycardia Substrate.

BACKGROUND: We sought to evaluate the safety and feasibility of a minimally fluoroscopic approach using the CARTOUNIVU module during scar-related ventricular tachycardia (VT) ablation. METHODS AND RESULTS: Consecutive patients with structural heart disease undergoing VT ablation using the CARTOUNIVU module were prospectively included and classified depending on their VT substrate: (1) ischemic VT (IVT) and (2) nonischemic VT and depending on the presence of an epicardial access. Radiation exposure parameters and major and minor procedure-related complications were registered. A near-zero fluoroscopy exposure was defined as those procedures with an effective dose ≤1 mSv. A total of 44 VT ablation procedures were performed in 41 patients (22 IVT and 19 nonischemic VT). The use of the CARTOUNIVU module resulted in low levels of radiation exposure: median total fluoroscopy time and effective dose of 6.08 (1.51-12.36) minutes and 2.15 (0.58-8.22) mSv, respectively. Patients with IVT had lower radiation exposure than patients with nonischemic VT (total fluoroscopy time, 2.53 [1.22-11.22] versus 8.51 [5.55-17.34] minutes; P=0.016). Epicardial access was associated with significantly higher levels of radiation exposure. Complications occurred in 4.9% patients, none of them being related to the use of the image integration tool. A near-zero fluoroscopy ablation could be performed in 14 of 44 procedures (32%), 43% of IVT procedures, and 50% of procedures with endocardial access only. CONCLUSIONS: The use of the CARTOUNIVU module during scar-related VT ablation resulted in low levels of radiation exposure. A near-zero fluoroscopy approach can be achieved in up to half of the procedures, especially in IVT patients with endocardial ablation.

Electrical Isolation of Pulmonary Veins Using Laser Catheter in the Treatment of Paroxysmal and Persistent Atrial Fibrillation. One-year Results.

INTRODUCTION AND OBJECTIVES: A new laser balloon that allows visualization of atrial tissue has recently been introduced for pulmonary vein electrical isolation. The aim of this study was to evaluate the mid-term safety and efficacy of this catheter in the treatment of atrial fibrillation. METHODS: Laser balloon ablation was performed in 71 patients with paroxysmal (80%) or persistent (20%) atrial fibrillation. Arrhythmia recurrence was defined as any episode lasting longer than 30 seconds. During follow-up, regular visits were performed every 3 months with 24- to 48-hour Holter tests. RESULTS: Isolation was possible in 275 of 278 (99%) of pulmonary veins. Mean procedure and fluoroscopy times were 154 ± 25 and 34 ± 15minutes, respectively. A total of 89% of veins were isolated during the first attempt. The most common complication was phrenic nerve paralysis (5.6%), which appeared in only the first 18 cases. A total of 59 patients received follow-up for a mean of 420 ± 193 days, with a rate of arrhythmia recurrence of 12% and 30%, respectively, in paroxysmal and persistent atrial fibrillation (P = .155). CONCLUSIONS: The laser balloon is a safe and effective system for pulmonary vein electrical isolation. Its advantages include the capacity to adapt to pulmonary vein anatomy using a single catheter, the efficacy with which pulmonary vein electrical isolation is achieved, and the favorable mid-term clinical progress, even for patients with persistent atrial fibrillation.

Gene expression network analysis reveals new transcriptional regulators as novel factors in human ischemic cardiomyopathy.

BACKGROUND: Ischemic cardiomyopathy (ICM) is characterized by transcriptomic changes that alter cellular processes leading to decreased cardiac output. Because the molecular network of ICM is largely unknown, the aim of this study was to characterize the role of new transcriptional regulators in the molecular mechanisms underlying the responses to ischemia. METHODS: Myocardial tissue explants from ICM patients and control (CNT) subjects were analyzed by RNA-Sequencing (RNA-Seq) and quantitative Real-Time PCR. RESULTS: Enrichment analysis of the ICM transcriptomic profile allowed the characterization of novel master regulators. We found that the expression of the transcriptional regulators SP100 (-1.5-fold, p < 0.05), CITED2 (-3.8-fold, p < 0.05), CEBPD (-4.9-fold, p < 0.05) and BCL3 (-3.3-fold, p < 0.05) were lower in ICM than in CNT. To gain insights into the molecular network defined by the transcription factors, we identified CEBPD, BCL3, and HIF1A target genes in the RNA-Seq datasets. We further characterized the biological processes of the target genes by gene ontology annotation. Our results suggest that CEBPD-inducible genes with roles in the inhibition of apoptosis are downregulated and that BCL3-repressible genes are involved in the regulation of cellular metabolism in ICM. Moreover, our results suggest that CITED2 downregulation causes increased expression of HIF1A target genes. Functional analysis of HIF1A target genes revealed that hypoxic and stress response genes are activated in ICM. Finally, we found a significant correlation between the mRNA levels of BCL3 and the mRNA levels of both CEBPD (r = 0.73, p < 0.001) and CITED2 (r = 0.56, p < 0.05). Interestingly, CITED2 mRNA levels are directly related to ejection fraction (EF) (r = 0.54, p < 0.05). CONCLUSIONS: Our data indicate that changes in the expression of SP100, CITED2, CEBPD, and BCL3 affect their transcription regulatory networks, which subsequently alter a number of biological processes in ICM patients. The relationship between CITED2 mRNA levels and EF emphasizes the importance of this transcription factor in ICM. Moreover, our findings identify new mechanisms used to interpret gene expression changes in ICM and provide valuable resources for further investigation of the molecular basis of human cardiac ischemic response.

Initial Experience with a New Image Integration Module Designed for Reducing Radiation Exposure During Electrophysiological Ablation Procedures.

INTRODUCTION: Reduction of radiation exposure during cardiac arrhythmia ablation procedures is desirable. We sought to evaluate the utility of a new image integration module (CARTOUNIVU(TM) ) in reducing fluoroscopy times and dosages during left atrial arrhythmia (LAA) and ventricular tachycardia (VT) ablation procedures. METHODS AND RESULTS: Consecutive patients undergoing LAA (n = 28)/VT (n = 13) ablation using the CARTOUNIVU(TM) module were included. Total fluoroscopy time, radiation dose (total dose area product [tDAP], effective dose [ED]), and procedure duration were evaluated. A retrospective cohort of patients who underwent LAA (n = 16)/VT(n = 8) ablation without the new image integration module served as a control group. The use of the new image integration module significantly reduced mean fluoroscopy time (5.2 minutes [IQR 1.9;6.8] in the LAA ablation UNIVU group vs. 28.2 minutes [IQR 15.3;37.8] in the control group, P<0.001; 9.8 minutes [IQR 4.5;13.1] vs. 25.5 minutes [IQR 14.1;30.9] for VT ablation, P = 0.013), tDAP (2,088 cGy*cm(2) [IQR 664;2911] vs. 5,893 cGy*cm(2) [IQR 3088;8483], P< 0.001 for LAA ablation; 3,917 cGy*cm(2) [IQR 948;4217] vs. 12,377 cGy*cm(2) (IQR 3385;23157) for VT ablation patients, P = 0.025) and ED (4.1 mSv [IQR 1;5.8] vs. 11.8 mSv [IQR 6.2;16.9] for LAA ablation patients, P< 0.001; 7.8 mSv [IQR 1.9;8.4] vs. 24.7 mSv [IQR 6.8;46.3] for VT ablation patients, P = 0.025). Procedure duration did not significantly change (174 ± 45 minutes vs. 197 ± 36 minutes for LAA ablation, P = 0.083; 201 ± 51 minutes vs. 201 ± 63 minutes for VT ablation, P = 0.860). No serious adverse events related to the use of the CARTOUNIVU(TM) module occurred. CONCLUSIONS: The new image integration module significantly reduced total fluoroscopy time and mean radiation dose without influence in procedure duration during ablation of complex atrial and ventricular arrhythmias.