Polypill Strategy in Secondary Cardiovascular Prevention.

BACKGROUND: A polypill that includes key medications associated with improved outcomes (aspirin, angiotensin-converting-enzyme [ACE] inhibitor, and statin) has been proposed as a simple approach to the secondary prevention of cardiovascular death and complications after myocardial infarction. METHODS: In this phase 3, randomized, controlled clinical trial, we assigned patients with myocardial infarction within the previous 6 months to a polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg), ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal type 1 myocardial infarction, or nonfatal ischemic stroke. RESULTS: A total of 2499 patients underwent randomization and were followed for a median of 36 months. A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; 95% confidence interval [CI], 0.60 to 0.96; P = 0.02). A key secondary-outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the usual-care group (hazard ratio, 0.70; 95% CI, 0.54 to 0.90; P = 0.005). The results were consistent across prespecified subgroups. Medication adherence as reported by the patients was higher in the polypill group than in the usual-care group. Adverse events were similar between groups. CONCLUSIONS: Treatment with a polypill containing aspirin, ramipril, and atorvastatin within 6 months after myocardial infarction resulted in a significantly lower risk of major adverse cardiovascular events than usual care. (Funded by the European Union Horizon 2020; SECURE ClinicalTrials.gov number, NCT02596126; EudraCT number, 2015-002868-17.).

Variable Penetrance and Expressivity of a Rare Pore Loss-of-Function Mutation (p.L889V) of Nav1.5 Channels in Three Spanish Families.

A novel rare mutation in the pore region of Nav1.5 channels (p.L889V) has been found in three unrelated Spanish families that produces quite diverse phenotypic manifestations (Brugada syndrome, conduction disease, dilated cardiomyopathy, sinus node dysfunction, etc.) with variable penetrance among families. We clinically characterized the carriers and recorded the Na+ current (INa) generated by p.L889V and native (WT) Nav1.5 channels, alone or in combination, to obtain further insight into the genotypic-phenotypic relationships in patients carrying SCN5A mutations and in the molecular determinants of the Nav1.5 channel function. The variant produced a strong dominant negative effect (DNE) since the peak INa generated by p.L889V channels expressed in Chinese hamster ovary cells, either alone (-69.4 ± 9.0 pA/pF) or in combination with WT (-62.2 ± 14.6 pA/pF), was significantly (n ≥ 17, p < 0.05) reduced compared to that generated by WT channels alone (-199.1 ± 44.1 pA/pF). The mutation shifted the voltage dependence of channel activation and inactivation to depolarized potentials, did not modify the density of the late component of INa, slightly decreased the peak window current, accelerated the recovery from fast and slow inactivation, and slowed the induction kinetics of slow inactivation, decreasing the fraction of channels entering this inactivated state. The membrane expression of p.L889V channels was low, and in silico molecular experiments demonstrated profound alterations in the disposition of the pore region of the mutated channels. Despite the mutation producing a marked DNE and reduction in the INa and being located in a critical domain of the channel, its penetrance and expressivity are quite variable among the carriers. Our results reinforce the argument that the incomplete penetrance and phenotypic variability of SCN5A loss-of-function mutations are the result of a combination of multiple factors, making it difficult to predict their expressivity in the carriers despite the combination of clinical, genetic, and functional studies.

Clinical and economic outcomes of a systematic same-day discharge programme after pulmonary vein isolation: comparison between cryoballoon vs. radiofrequency ablation.

AIMS: Same-day discharge (SDD) is feasible after pulmonary vein isolation (PVI). We aim to compare prospectively cryoballoon (CRYO) vs. radiofrequency (RF) ablation in a systematic SDD programme. METHODS AND RESULTS: We prospectively analysed the 617 scheduled PVI performed consecutively at our institution (n = 377 CRYO, n = 240 RF) from 1 April 2019 to 31 December 2022 within a systematic programme of SDD. The feasibility of SDD, the 10-day incidence of urgent/unplanned medical care after discharge (UUC-10), and the cost per procedure due to hospital resource use were studied. The 100 procedures performed during the previous year, in which patients were systematically hospitalized, were used as a control group. Same-day discharge was achieved in 585/617 (95%) procedures, with a significant trend towards a higher monthly SDD rate from 2019 to 2022 (P = 0.03). The frequency of SDD was similar in CRYO (356/377; 94%) vs. RF (229/240; 95%). After SDD, the UUC-10 was 66/585 (11.3%), being similar for CRYO (41/356; 11.5%) and RF (25/229; 10.9%); P = 0.8 (log-rank test). Of these, 10 patients were re-hospitalized, with an identical rate in CRYO-treated (6/356; 1.7%) and RF-treated (4/229; 1.7%) patients and owing to similar causes (4 haematomas, 4 pericarditis, and 2 symptomatic sinus node dysfunction). Same-day discharge was associated with an average savings per procedure of 63% (P < 0.001), but no differences were found between the CRYO and RF (P = 0.8). CONCLUSION: In a systematic SDD programme, feasibility (95%, increasing over time), safety (11% UUC-10, 1.7% re-hospitalizations), and savings (63% per procedure) were similar for CRYO and RF ablation procedures.

Short-term mechanical circulatory support in elderly patients.

BACKGROUND: Age over 70 years seems to confer poor prognosis for patients under mechanical circulatory support (MCS). Advanced age is usually a relative contraindication. Our objective was to assess the impact of age on survival of patients with short-term MCS. METHODS: Retrospective analysis of ≥70-year-old patients supported with veno-arterial extracorporeal membrane oxygenation (VA-ECMO) or Impella CP® due to cardiogenic shock and other situations of hemodynamic instability in a referral hospital (elderly group), compared with younger patients (<70 years). We analyze factors associated with survival in elderly group. RESULTS: Out of 164 short-term MCS implants from 2013 to October 2020, 45 (27.4%) correspond to ≥70-year-old patients (73.3% VA-ECMO; 26.7% Impella CP®), 80% as bridge to recovery and 15.6% for high-risk percutaneous coronary intervention (PCI). We found no significant differences in complications developed between both groups. Survivals at discharge (40% vs. 43.7%, p = 0.403) and at follow-up (median 13.6 [30] months) were similar in elderly and young patients (35.6% vs. 37.8%, log-rank p = 0.061). Predictive factors of mortality in elderly patients were peripheral artery disease (p = 0.037), higher lactate (p = 0.003) and creatinine (p = 0.035) at implant, longer cardiac arrest (p = 0.003), and worse post-implantation left ventricular ejection fraction (p = 0.003). Patients with indication of MCS for high-risk PCI had higher survival compared to other indications (p = 0.013). CONCLUSION: Short-term MCS with VA-ECMO or Impella CP® in elderly patients may be a reasonable option in hemodynamic compromise situations as bridge to recovery or elective high-risk PCI, without a significant increase in complications or mortality. Age should not be an absolute contraindication, but careful selection of candidate patients is necessary.

Predictive Model and Risk Score for In-Hospital Mortality in Patients with All-Cause Cardiogenic Shock.

Cardiogenic shock (CS) is a condition associated with high morbidity and mortality. Our study aimed to perform a risk score for in-hospital mortality that allows for stratifying the risk of death in patients with CS.This is a retrospective analysis, which included 135 patients from a Spanish university hospital between 2011 and 2020. The Santiago Shock Score (S3) was created using clinical, analytical, and echocardiographic variables obtained at the time of admission.The in-hospital mortality rate was 41.5%, and acute coronary syndrome (ACS) was the responsible cause of shock in 60.7% of patients. Mitral regurgitation grade III-IV, age, ACS etiology, NT-proBNP, blood hemoglobin, and lactate at admission were included in the score. The S3 had good accuracy for predicting in-hospital mortality area under the receiver operating characteristic curve (AUC) 0.85 (95% confidence interval (CI) 0.78-0.90), higher than the AUC of the CardShock score, which was 0.74 (95% CI 0.66-0.83). Predictive power in a cohort of 131 patients with profound CS was similar to that of CardShock with an AUC of 0.601 (95% CI 0.496-0.706) versus an AUC of 0.558 (95% CI 0.453-0.664). Three risk categories were created according to the S3: low (scores 0-6), intermediate (scores 7-10), and high (scores 11-16) risks, with an observed mortality of 12.9%, 49.1%, and 87.5% respectively (P < 0.001).The S3 score had excellent predictive power for in-hospital mortality in patients with nonprofound CS. It could aid the initial risk stratification of patients and thus, guide treatment and clinical decision making in patients with CS.

Predictors of cardiovascular events and all-cause of death in patients with transfusion-dependent myelodysplastic syndrome.

Cardiovascular disease (CVD) involves the second cause of death in low-risk myelodysplastic syndrome (MDS) population. Prospective study to characterise the CVD and to identify predictors for the combined event (CE) cardiovascular event and/or all-cause mortality in transfusion dependent low-risk MDS patients. Thirty-one patients underwent a cardiac assessment including biomarkers and cardiac magnetic resonance (cMR) with parametric sequences (T1, T2 and T2* mapping) and myocardial deformation by feature tracking (FT) and were analysed for clonal hematopoiesis of indeterminate potential mutations. Cardiac assessment revealed high prevalence of unknown structural heart disease (51% cMR pathological findings). After 2·2 [0·44] years follow-up, 35·5% of patients suffered the CE: 16% death, 29% cardiovascular event. At multivariate analysis elevated NT-proBNP ≥ 486pg/ml (HR 96·7; 95%-CI 1·135-8243; P = 0·044), reduced native T1 time < 983ms (HR 44·8; 95%-CI 1·235-1623; P = 0·038) and higher left ventricular global longitudinal strain (LV-GLS) (HR 0·4; 95%-CI 0·196-0·973; P = 0·043) showed an independent prognostic value. These variables, together with the myocardial T2* time < 20ms, showed an additive prognostic value (Log Rank: 12·4; P = 0·001). In conclusion, low-risk MDS patients frequently suffer CVD. NT-proBNP value, native T1 relaxation time and longitudinal strain by FT are independent predictors of poor cardiovascular prognosis, thus, their determination would identify high-risk patients who could benefit from a cardiac treatment and follow-up.

Cycle length of nonsustanied ventricular tachycardias among ICD patients: implications on subsequent appropriate therapies.

BACKGROUND: ICD patients with episodes of nonsustained ventricular tachycardias (NSVT) are at risk of appropriate therapies. However, the relationship between the cycle length (CL) of such NSVTs and the subsequent incidence of appropriate interventions is unknown. METHODS: 416 ICD patients with LVEF < 45% were studied. ICD programming was standardized. NSVT was defined as any VT of 5 or more beats at ≥ 150 bpm occurred in the first 6 months after implantation that terminated spontaneously and was not preceded by any appropriate therapy. The mean follow-up was 41 ± 27 months. RESULTS: We analyzed 2201 NSVTs (mean CL = 323 ms) that occurred in 250 patients; 111 of such episodes were fast (CL ≤ 300 ms). Secondary prevention (HR = 1.7; p < 0.001), number of NSVT episodes (HR = 1.05; 95% CI 1.04-1.07; p < 0.001) and beta-blocker treatment (HR = 0.7; p = 0.04) were independent predictors of appropriate interventions; however, the mean CL of NSVTs was not (p = 0.6). There was a correlation between the mean CL of NSVTs and the CL of the first monomorphic VT: r = 0.88; p < 0.001. This correlation was especially robust in individuals with > 5 NSVTs (r = 0.97; p < 0.001), with an agreement between both values greater than 95%. Patients with any fast NSVT experienced a higher incidence of VF episodes (26%) compared to those without NVSTs (3%) or with only slow NSVTs (7%); p < 0.001. CONCLUSIONS: Unlike the burden, the CL of NSVTs is not a predictor of subsequent appropriate interventions. However, there is a close relationship between the CL of NSVTs and that of arrhythmias that will later lead to appropriate therapies.

Levosimendan in veno-arterial extracorporeal membrane oxygenator supported patients: Impact on the success of weaning and survival.

Weaning failure and mortality rates in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) supported patients are significant. Small studies suggest the possible usefulness of levosimendan in this environment, especially in postcardiotomy shock. We performed a retrospective analysis of VA-ECMO implants in a referral hospital comparing weaning failure and survival of patients treated with levosimendan with a control group. From 2013 to May 2020, 123 VA-ECMO for several indications were implanted. Levosimendan was administered in 23 patients (18.7%) with good tolerance. Levosimendan was used more frequently in cardiogenic shock due to acute coronary syndrome indication, and in patients with lower left ventricular ejection fraction (LVEF) at the implant. No significant differences were found in success of ECMO weaning (60.9% levosimendan group vs. 44% non-levosimendan group, P = .169) despite worse LVEF in levosimendan group. Survival at follow-up (20.6 [58] months) was higher in the group that received levosimendan, although without finding statistically significant differences (47.8% vs. 32.0%, log rank P = .124). Levosimendan can be safely administered during VA-ECMO support. Patients receiving levosimendan were weaned similarly from circulatory support despite worse LVEF. Its use did not influence in short- and medium-term survival. Randomized studies are needed to evaluate the levosimendan impact in this indication.

Prevalence of coronary atherosclerosis and reclassification of cardiovascular risk in Spanish population by coronary computed tomography angiography: EVA study.

BACKGROUND: A more complete assessment of coronary artery disease (CAD) can be performed by coronary computed tomography angiography (CCTA). The aim was to assess the prevalence, distribution and characteristics of coronary artery disease (CAD) and the reclassification of cardiovascular risk by CCTA in an asymptomatic Spanish population. DESIGN: We included, in a cross-sectional study, 501 random subjects from asymptomatic population, aged 35 and 75. Risk factors, target organ damage and cardiovascular risk were assessed. CCTA was offered to measure the coronary artery calcium score(CACS), segment involvement score(SIS) and segment stenosis score(SSS). The offer was accepted by 220 subjects (44%), with a mean age of 58 ± 14 years, 56% of them male. RESULTS: The mean CACS was 119.6 ± 381.7 (median (IQR) (0 (0-61.55))), with higher scores in males (191.9 ± 493.1) than females (26.1 ± 73.3; P < .01). CCTA revealed coronary atherosclerosis in 89 cases, 40% (CI95%:34%-46%) in global, 51% in male and 25% in female, of which 13 had obstructive lesions (5.9%). Mean SIS was 1.5 ± 2.5 and SSS 1.2 ± 3.1. When the CACS was included in the CAD risk scale, there was a reclassification of 24%, and when using the SIS percentile, it was 38%, with a 9% increase in risk in both cases. CONCLUSIONS: The prevalence of CAD in asymptomatic Spanish population was 40%, with greater proportion among males. The incorporation of CACS and SIS in the assessment of cardiovascular risk allows reclassifying subjects who are at low or moderate risk and thus identify those with high cardiovascular risk and also the other way.

Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With ST-Segment Elevation Myocardial Infarction and Left Ventricular Dysfunction.

RATIONALE: Allogeneic cardiac stem cells (AlloCSC-01) have shown protective, immunoregulatory, and regenerative properties with a robust safety profile in large animal models of heart disease. OBJECTIVE: To investigate the safety and feasibility of early administration of AlloCSC-01 in patients with ST-segment-elevation myocardial infarction. METHODS AND RESULTS: CAREMI (Safety and Efficacy of Intracoronary Infusion of Allogeneic Human Cardiac Stem Cells in Patients With STEMI and Left Ventricular Dysfunction) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial in patients with ST-segment-elevation myocardial infarction, left ventricular ejection fraction ≤45%, and infarct size ≥25% of left ventricular mass by cardiac magnetic resonance, who were randomized (2:1) to receive AlloCSC-01 or placebo through the intracoronary route at days 5 to 7. The primary end point was safety and included all-cause death and major adverse cardiac events at 30 days (all-cause death, reinfarction, hospitalization because of heart failure, sustained ventricular tachycardia, ventricular fibrillation, and stroke). Secondary safety end points included major adverse cardiac events at 6 and 12 months, adverse events, and immunologic surveillance. Secondary exploratory efficacy end points were changes in infarct size (percentage of left ventricular mass) and indices of ventricular remodeling by magnetic resonance at 12 months. Forty-nine patients were included (92% male, 55±11 years), 33 randomized to AlloCSC-01 and 16 to placebo. No deaths or major adverse cardiac events were reported at 12 months. One severe adverse events in each group was considered possibly related to study treatment (allergic dermatitis and rash). AlloCSC-01 elicited low levels of donor-specific antibodies in 2 patients. No immune-related adverse events were found, and no differences between groups were observed in magnetic resonance-based efficacy parameters at 12 months. The estimated treatment effect of AlloCSC-01 on the absolute change from baseline in infarct size was -2.3% (95% confidence interval, -6.5% to 1.9%). CONCLUSIONS: AlloCSC-01 can be safely administered in ST-segment-elevation myocardial infarction patients with left ventricular dysfunction early after revascularization. Low immunogenicity and absence of immune-mediated events will facilitate adequately powered studies to demonstrate their clinical efficacy in this setting. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02439398.

Effect of Ischemia Duration and Protective Interventions on the Temporal Dynamics of Tissue Composition After Myocardial Infarction.

RATIONALE: The impact of cardioprotective strategies and ischemia duration on postischemia/reperfusion (I/R) myocardial tissue composition (edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction) is not well understood. OBJECTIVE: To study the effect of ischemia duration and protective interventions on the temporal dynamics of myocardial tissue composition in a translational animal model of I/R by the use of state-of-the-art imaging technology. METHODS AND RESULTS: Four 5-pig groups underwent different I/R protocols: 40-minute I/R (prolonged ischemia, controls), 20-minute I/R (short-duration ischemia), prolonged ischemia preceded by preconditioning, or prolonged ischemia followed by postconditioning. Serial cardiac magnetic resonance (CMR)-based tissue characterization was done in all pigs at baseline and at 120 minutes, day 1, day 4, and day 7 after I/R. Reference myocardium at risk was assessed by multidetector computed tomography during the index coronary occlusion. After the final CMR, hearts were excised and processed for water content quantification and histology. Five additional healthy pigs were euthanized after baseline CMR as reference. Edema formation followed a bimodal pattern in all 40-minute I/R pigs, regardless of cardioprotective strategy and the degree of intramyocardial hemorrhage or microvascular obstruction. The hyperacute edematous wave was ameliorated only in pigs showing cardioprotection (ie, those undergoing short-duration ischemia or preconditioning). In all groups, CMR-measured edema was barely detectable at 24 hours postreperfusion. The deferred healing-related edematous wave was blunted or absent in pigs undergoing preconditioning or short-duration ischemia, respectively. CMR-measured infarct size declined progressively after reperfusion in all groups. CMR-measured myocardial salvage, and the extent of intramyocardial hemorrhage and microvascular obstruction varied dramatically according to CMR timing, ischemia duration, and cardioprotective strategy. CONCLUSIONS: Cardioprotective therapies, duration of index ischemia, and the interplay between these greatly influence temporal dynamics and extent of tissue composition changes after I/R. Consequently, imaging techniques and protocols for assessing edema, myocardium at risk, infarct size, salvage, intramyocardial hemorrhage, and microvascular obstruction should be standardized accordingly.

Dynamic Edematous Response of the Human Heart to Myocardial Infarction: Implications for Assessing Myocardial Area at Risk and Salvage.

BACKGROUND: Clinical protocols aimed to characterize the post-myocardial infarction (MI) heart by cardiac magnetic resonance (CMR) need to be standardized to take account of dynamic biological phenomena evolving early after the index ischemic event. Here, we evaluated the time course of edema reaction in patients with ST-segment-elevation MI by CMR and assessed its implications for myocardium-at-risk (MaR) quantification both in patients and in a large-animal model. METHODS: A total of 16 patients with anterior ST-segment-elevation MI successfully treated by primary angioplasty and 16 matched controls were prospectively recruited. In total, 94 clinical CMR examinations were performed: patients with ST-segment-elevation MI were serially scanned (within the first 3 hours after reperfusion and at 1, 4, 7, and 40 days), and controls were scanned only once. T2 relaxation time in the myocardium (T2 mapping) and the extent of edema on T2-weighted short-tau triple inversion-recovery (ie, CMR-MaR) were evaluated at all time points. In the experimental study, 20 pigs underwent 40-minute ischemia/reperfusion followed by serial CMR examinations at 120 minutes and 1, 4, and 7 days after reperfusion. Reference MaR was assessed by contrast-multidetector computed tomography during the index coronary occlusion. Generalized linear mixed models were used to take account of repeated measurements. RESULTS: In humans, T2 relaxation time in the ischemic myocardium declines significantly from early after reperfusion to 24 hours, and then increases up to day 4, reaching a plateau from which it decreases from day 7. Consequently, edema extent measured by T2-weighted short-tau triple inversion-recovery (CMR-MaR) varied with the timing of the CMR examination. These findings were confirmed in the experimental model by showing that only CMR-MaR values for day 4 and day 7 postreperfusion, coinciding with the deferred edema wave, were similar to values measured by reference contrast-multidetector computed tomography. CONCLUSIONS: Post-MI edema in patients follows a bimodal pattern that affects CMR estimates of MaR. Dynamic changes in post-ST-segment-elevation MI edema highlight the need for standardization of CMR timing to retrospectively delineate MaR and quantify myocardial salvage. According to the present clinical and experimental data, a time window between days 4 and 7 post-MI seems a good compromise solution for standardization. Further studies are needed to study the effect of other factors on these variables.

Does renal function affect the efficacy or safety of a pharmacoinvasive strategy in patients with ST-elevation myocardial infarction? A meta-analysis.

BACKGROUND: The efficacy and safety of pharmacoinvasive strategy following fibrinolysis for ST-elevation myocardial infarction (STEMI) in relation to renal function have not been established. METHODS: Using patient-level data from 4 randomized controlled trials, we examined the efficacy and safety of pharmacoinvasive versus standard treatment after fibrinolysis for STEMI. Patients were stratified based on the estimated glomerular filtration rate (eGFR) on presentation (<60 mL/min/1.73 m2 vs ≥60 mL/min/1.73 m2). The primary outcome was the composite of death or reinfarction at 30 days. RESULTS: Of 2,029 patients, 457 (23%) had an eGFR<60 mL/min/1.73 m2. Patients with eGFR<60 mL/min/1.73 m2 were older and had higher Thrombolysis in Myocardial Infarction risk scores. Compared with patients with eGFR≥60 mL/min/1.73 m2, patients with renal dysfunction had higher rates of the primary outcome (5.3% vs 11.8%, respectively; P<.001). There was no significant heterogeneity in the treatment effect of pharmacoinvasive strategy on the primary outcome (P heterogeneity=.73) or the rate of death or reinfarction at 1 year (P heterogeneity=.64) in relation to eGFR. Patients with renal dysfunction had higher rates of in-hospital major bleeding compared with patients with eGFR ≥60 mL/min/1.73 m2 (7.7% vs 4.3%, respectively; P=.004); however, there was no difference in bleeding events between treatment arms in the overall cohort or in relation to eGFR (P heterogeneity=.67). CONCLUSIONS: Renal impairment is associated with increased rates of adverse events in STEMI patients treated with fibrinolysis. However, the safety and efficacy of pharmacoinvasive strategy are preserved in patients with renal impairment on presentation.

Brain natriuretic peptide levels variation after left atrial appendage occlusion.

OBJECTIVE: To explore the variations of brain natriuretic peptide (BNP) secretion after left atrial appendage occlusion. BACKGROUND: Left atrial appendage occlusion has been increasingly performed in the last few years, however little is known about the physiological consequences of left atrial appendage occlusion. Left atrial appendage regulates partially intravascular volume via release of brain natriuretic peptide. Brain natriuretic peptide levels have been related to increased risk of stroke in atrial fibrillation patients. METHODS: Venous blood samples were obtained in consecutive patients undergoing left atrial appendage occlusion before, 24 hr after device implantation and at the first visit after discharge (45-60 days) for BNP measurement. RESULTS: Left atrial appendage occlusion was performed in 34 patients with non-valvular atrial fibrillation and contraindication to long-term oral anticoagulation or at high-risk of bleeding. There were no differences in BNP levels between baseline and 24 hr after device implantation. However left atrial appendage closure resulted in a significant decrease in BNP levels at the first follow-up visit (45-60 days) compared to baseline measurements (759.90 pg ml(-1) vs. 636.90 pg ml(-1) , P = 0.013). CONCLUSIONS: Left atrial appendage occlusion modifies BNP levels. These levels decrease after left atrial appendage occlusion. The clinical consequences of these findings need to be evaluated in further studies. © 2015 Wiley Periodicals, Inc.

Percutaneous Closure of Paravalvular Leaks: A Systematic Review.

Paravalvular leak (PVL) is an uncommon yet serious complication associated with the implantation of mechanical or bioprosthetic surgical valves and more recently recognized with transcatheter aortic valves implantation (TAVI). A significant number of patients will present with symptoms of congestive heart failure or haemolytic anaemia due to PVL and need further surgical or percutaneous treatment. Until recently, surgery has been the only available therapy for the treatment of clinically significant PVLs despite the significant morbidity and mortality associated with re-operation. Percutaneous treatment of PVLs has emerged as a safe and less invasive alternative, with low complication rates and high technical and clinical success rates. However, it is a complex procedure, which needs to be performed by an experienced team of interventional cardiologists and echocardiographers. This review discusses the current understanding of PVLs, including the utility of imaging techniques in PVL diagnosis and treatment, and the principles, outcomes and complications of transcatheter therapy of PVLs.

Utility of Real-Time 3-Dimensional Transesophageal Echocardiography in the Assessment of Mitral Paravalvular Leak.

BACKGROUND: Mitral paravalvular leak (PVL) is a potential complication of surgical valve replacement procedures. Real-time 3D transesophageal echocardiography (RT-3DTEE) has emerged as an efficient tool for providing essential information about the anatomy of mitral PVLs compared with 2DTEE findings. The purpose of this study was to evaluate the utility of RT-3DTEE in the assessment of mitral PVLs. METHODS AND RESULTS: The 3D characteristics of PVLs were recorded and compared with 2D findings. We included 34 consecutive patients with clinical suspicion of mitral PVL in the study. Mitral PVLs were detected in 26 patients (76%); 26 PVLs were identified by 2DTEE and 37 by RT-3DTEE. Moderate or severe mitral regurgitation was present in 23 patients (88%). The most common PVL locations were the septal and posterior regions. The median PVL size measured by RT-3DTEE was 7 mm long×4 mm wide. The median vena contracta of defect measured by 2DTEE and RT-3DTEE was 5 mm and 4 mm, respectively. The median effective regurgitant orifice area of defect measured by RT-3DTEE was 0.36 cm(2). The defect types were "oval" (54%), "round" (35%), "crescentic" (8%) and highly irregular (3%). CONCLUSIONS: Compared with 2DTEE, RT-3DTEE provided detailed descriptions of the number, location, size and morphology of PVLs, which is essential for planning and guiding the potential corrective techniques. (Circ J 2016; 80: 738-744).

Pulmonary Vein Occlusion Successfully Treated by Stenting with Intravascular Ultrasound Guidance.

Pulmonary vein (PV) stenosis (PVS) is a known complication of PV isolation procedures for AF (atrial fibrillation). PV angioplasty and stenting have been used as an effective therapy for PVS, yet high rates of restenosis are common. Experience with intravascular ultrasound (IVUS) in evaluating the PVS morphological characteristics and appropriate stent deployment is very limited. Furthermore, the use of IVUS could minimise the risk of restenosis. We describe the case of a patient with sub-occlusion of the left superior PV and total occlusion of the left inferior PV following catheter ablation for AF treated by stenting with IVUS guidance.