Sbk2, a Newly Discovered Atrium-Enriched Regulator of Sarcomere Integrity.

BACKGROUND: Heart development relies on tight spatiotemporal control of cardiac gene expression. Genes involved in this intricate process have been identified using animals and pluripotent stem cell-based models of cardio(myo)genesis. Recently, the repertoire of cardiomyocyte differentiation models has been expanded with iAM-1, a monoclonal line of conditionally immortalized neonatal rat atrial myocytes (NRAMs), which allows toggling between proliferative and differentiated (ie, excitable and contractile) phenotypes in a synchronized and homogenous manner. METHODS: In this study, the unique properties of conditionally immortalized NRAMs (iAMs) were exploited to identify and characterize (lowly expressed) genes with an as-of-yet uncharacterized role in cardiomyocyte differentiation. RESULTS: Transcriptome analysis of iAM-1 cells at different stages during one cycle of differentiation and subsequent dedifferentiation identified ≈13 000 transcripts, of which the dynamic changes in expression upon cardiomyogenic differentiation mostly opposed those during dedifferentiation. Among the genes whose expression increased during differentiation and decreased during dedifferentiation were many with known (lineage-specific) functions in cardiac muscle formation. Filtering for cardiac-enriched low-abundance transcripts, identified multiple genes with an uncharacterized role during cardio(myo)genesis including Sbk2 (SH3 domain binding kinase family member 2). Sbk2 encodes an evolutionarily conserved putative serine/threonine protein kinase, whose expression is strongly up- and downregulated during iAM-1 cell differentiation and dedifferentiation, respectively. In neonatal and adult rats, the protein is muscle-specific, highly atrium-enriched, and localized around the A-band of cardiac sarcomeres. Knockdown of Sbk2 expression caused loss of sarcomeric organization in NRAMs, iAMs and their human counterparts, consistent with a decrease in sarcomeric gene expression as evinced by transcriptome and proteome analyses. Interestingly, co-immunoprecipitation using Sbk2 as bait identified possible interaction partners with diverse cellular functions (translation, intracellular trafficking, cytoskeletal organization, chromatin modification, sarcomere formation). CONCLUSIONS: iAM-1 cells are a relevant and suitable model to identify (lowly expressed) genes with a hitherto unidentified role in cardiomyocyte differentiation as exemplified by Sbk2: a regulator of atrial sarcomerogenesis.

Myocardial infarction care in low and high socioeconomic environments: claims data analysis.

BACKGROUND: To date, claims data have not been used to study outcome differences between low and high socioeconomic status (SES) patients surviving ST-elevation myocardial infarction (STEMI) and non-ST-elevation myocardial infarction (NSTEMI) in the Netherlands. AIM: To evaluate STEMI and NSTEMI care among patients with low and high SES in the referral area of three Dutch percutaneous coronary intervention (PCI) centres, using claims data as a source. METHODS: STEMI and NSTEMI patients treated in 2015-2017 were included. Patients' SES scores were collected based on their postal code via an open access government database. In patients with low (SES1) and high (SES4) status, revascularisation strategies and secondary prevention medication were compared. RESULTS: A total of 2065 SES1 patients (age 68 ± 13 years, 58% NSTEMI) and 1639 SES4 patients (age 68 ± 13 years, 63% NSTEMI) were included. PCI use was lower in SES1 compared to SES4 in both STEMI (80% vs 84%, p < 0.012) and NSTEMI (42% vs 48%, p < 0.002) patients. Coronary artery bypass grafting was performed more often in SES1 than in SES4 in both STEMI (7% vs 4%, p = NS) and NSTEMI (11% vs 7%, p < 0.001) patients. Optimal medical therapy use in STEMI patients was higher in SES1 compared to SES4 (52% vs 46%, p = 0.01) but comparable among NSTEMI patients (39% vs 40%, p = NS). One-year mortality was comparable in SES1 and SES4 patients following STEMI (14% vs 16%, p = NS) and NSTEMI (10% vs 11%, p = NS). CONCLUSION: Combined analysis of claims data and area-specific socioeconomic statistics can provide unique insight into how to improve myocardial infarction care for low and high SES patients.

Improved prehospital triage for acute cardiac care: results from HART-c, a multicentre prospective study.

BACKGROUND: Cardiac symptoms are one of the most prevalent reasons for emergency department visits. However, over 80% of patients with such symptoms are sent home after acute cardiovascular disease has been ruled out. OBJECTIVE: The Hollands-Midden Acute Regional Triage-cardiology (HART-c) study aimed to investigate whether a novel prehospital triage method, combining prehospital and hospital data with expert consultation, could increase the number of patients who could safely stay at home after emergency medical service (EMS) consultation. METHODS: The triage method combined prehospital EMS data, such as electrocardiographic and vital parameters in real time, and data from regional hospitals (including previous medical records and admission capacity) with expert consultation. During the 6­month intervention and control periods 1536 and 1376 patients, respectively, were consulted by the EMS. The primary endpoint was the percentage change of patients who could stay at home after EMS consultation. RESULTS: The novel triage method led to a significant increase in patients who could safely stay at home, 11.8% in the intervention group versus 5.9% in the control group: odds ratio 2.31 (95% confidence interval (CI) 1.74-3.05). Of 181 patients staying at home, only 1 (< 1%) was later diagnosed with ACS; no patients died. Furthermore the number of interhospital transfers decreased: relative risk 0.81 (95% CI 0.67-0.97). CONCLUSION: The HART­c triage method led to a significant decrease in interhospital transfers and an increase in patients with cardiac symptoms who could safely stay at home. The presented method thereby reduced overcrowding and, if implemented throughout the country and for other medical specialties, could potentially reduce the number of cardiac and non-cardiac hospital visits even further.

Associations between left ventricular function, vascular function and measures of cerebral small vessel disease: a cross-sectional magnetic resonance imaging study of the UK Biobank.

OBJECTIVES: Impaired cardiovascular function has been associated with cognitive deterioration; however, to what extent cardiovascular dysfunction plays a role in structural cerebral changes remains unclear. We studied whether vascular and left ventricular (LV) functions are associated with measures of cerebral small vessel disease (cSVD) in the middle-aged general population. METHODS: In this cross-sectional analysis of the UK Biobank, 4366 participants (54% female, mean age 61 years) underwent magnetic resonance imaging to assess LV function (ejection fraction [EF] and cardiac index [CI]) and cSVD measures (total brain volume, grey and white matter volumes, hippocampal volume and white matter hyperintensities [WMH]). Augmentation index (AIx) was used as a measure of arterial stiffness. Linear and non-linear associations were evaluated using cardiovascular function measures as determinants and cSVD measures as outcomes. RESULTS: EF was non-linearly associated with total brain volume and grey matter volume, with the largest brain volume for an EF between 55 and 60% (both p < 0.001). EF showed a negative linear association with WMH (- 0.23% [- 0.44; - 0.02], p = 0.03), yet no associations were found with white matter or hippocampal volume. CI showed a positive linear association with white matter (ß 3194 mm3 [760; 5627], p = 0.01) and hippocampal volume (ß 72.5 mm3 [23.0; 122.0], p = 0.004). No associations were found for CI with total brain volume, grey matter volume or WMH. No significant associations were found between AIx and cSVD measures. CONCLUSIONS: This study provides novel insights into the complex associations between the heart and the brain, which could potentially guide early interventions aimed at improving cardiovascular function and the prevention of cSVD. KEY POINTS: • Ejection fraction is non-linearly and cardiac index is linearly associated with MRI-derived measures of cerebral small vessel disease. • No associations were found for arterial stiffness with cSVD measures.

Normal and reference values for cardiovascular magnetic resonance-based pulse wave velocity in the middle-aged general population.

BACKGROUND: Aortic stiffness, assessed through pulse wave velocity (PWV), is an independent predictor for cardiovascular disease risk. However, the scarce availability of normal and reference values for cardiovascular magnetic resonance imaging (CMR) based PWV is limiting clinical implementation. The aim of this study was to determine normal and reference values for CMR assessed PWV in the general population. METHODS: From the 2,484 participants of the Netherlands Epidemiology of Obesity (NEO) study that have available CMR-PWV data, 1,394 participants free from cardiovasculard disease, smokers or treatment for diabetes, hypertension or dyslipidaemia were selected (45-65 years, 51% female). Participants were divided into sex, age and blood pressure (BP) subgroups. Normal values were specified for participants with a BP < 130/80 mmHg and reference values for elevated BP subgroups (≥ 130/80 and < 140/90 mmHg; and ≥ 140/90 mmHg). Differences between groups were tested with independent samples t-test or ANOVA. Due to an oversampling of obese individuals in this study, PWV values are based on a weighted analysis making them representative of the general population. RESULTS: Normal mean PWV was 6.0 m/s [95% CI 5.8-6.1]. PWV increased with advancing age and BP categories (both p < 0.001). There was no difference between sex in normal PWV, however in the BP > 140/90 mmHg women had a higher PWV (p = 0.005). The interpercentile ranges were smaller for participants < 55 years old compared to participants ≥ 55 years, indicating an increasing variability of PWV with age. PWV upper limits were particularly elevated in participants ≥ 55 years old in the high blood pressure subgroups. CONCLUSION: This study provides normal and reference values for CMR-assessed PWV per sex, age and blood pressure category in the general population.

Myocardial calcification is associated with endocardial ablation failure of post-myocardial infarction ventricular tachycardia.

AIMS: In patients with post-myocardial infarction (post-MI) ventricular tachycardia (VT), the presence of myocardial calcification (MC) may prevent heating of a subepicardial VT substrate contributing to endocardial ablation failure. The aims of this study were to assess the prevalence of MC in patients with post-MI VT and evaluate the impact of MC on outcome after endocardial ablation. METHODS AND RESULTS: In 158 patients, the presence of MC was retrospectively assessed on fluoroscopy recordings in seven standard projections obtained during pre-procedural coronary angiograms. Myocardial calcification, defined as a distinct radiopaque area that moved synchronously with the cardiac contraction, was detected in 30 patients (19%). After endocardial ablation, only 6 patients (20%) with MC were rendered non-inducible compared with 56 (44%) without MC (P = 0.033) and of importance, 8 (27%) remained inducible for the clinical VT [compared with 9 (6%) patients without MC; P = 0.003] requiring therapy escalation. After a median follow-up of 31 months, 61 patients (39%) had VT recurrence and 47 (30%) died. Patients with MC had a lower survival free from the composite endpoint of VT recurrence or therapy escalation at 24-month follow-up (26% vs. 59%; P = 0.003). Presence of MC (HR 1.69; P = 0.046), a lower LV ejection fraction (HR 1.03 per 1% decrease; P = 0.017), and non-complete procedural success (HR 2.42; P = 0.002) were independently associated with a higher incidence of VT recurrence or therapy escalation. CONCLUSION: Myocardial calcification was present in 19% of post-MI patients referred for VT ablation and was associated with a high incidence of endocardial ablation failure.

The prognostic value of J-wave pattern for recurrence of ventricular tachycardia after catheter ablation in patients with myocardial infarction.

BACKGROUND: J-waves and fragmented QRS (fQRS) on surface ECGs have been associated with the occurrence of ventricular tachyarrhythmias. Whether these non-invasive parameters can also predict ventricular tachycardia (VT) recurrence after radiofrequency catheter ablation (RFCA) is unknown. Of interest, patients with a wide QRS-complex have been excluded from clinical studies on J-waves, although a J-wave like pattern has been described for wide QRS. METHODS: We retrospectively included 168 patients (67 ± 10 years; 146 men) who underwent RFCA of post-infarct VT. J-wave pattern were defined as J-point elevation ≥ 0.1 mV in at least two leads irrespective of QRS width. fQRS was defined as various RSR` pattern in patients with narrow QRS and more than two R wave in those with wide QRS. The primary endpoint was VT recurrence after RFCA up to 24 months. RESULTS: J-wave pattern and fQRS were present in 27 and 28 patients, respectively. Overlap of J-wave pattern and fQRS was observed in nine. During a median follow-up of 20 (interquartile range 9-24) months, 46 (27%) patients had VT recurrence. Kaplan-Meier curves revealed that both J-wave pattern and fQRS were associated with VT recurrence. Multivariate Cox regression analysis demonstrated that the presence of J-wave pattern (hazard ratio [HR] 2.84; 95% confidence interval [CI] 1.45-5.58; P = .002) and greater number of induced VT (HR 1.29; 95% CI 1.15-1.45; P < .001) were the independent predictors of VT recurrence. CONCLUSIONS: A J-wave pattern-but not fQRS-is independently associated with an increased risk of post-infarct VT recurrence after RFCA irrespective of QRS width. This simple non-invasive parameter may identify patients who require additional treatment.

Mechanical extraction of cardiac implantable electronic devices leads with long dwell time: Efficacy and safety of the step up approach.

The aim of this study was to evaluate the efficacy and safety of the stepwise mechanical transvenous lead extraction approach in a patient population with chronically implanted transvenous leads with a long dwell time. From January 2014 till December 2018, all lead extractions with lead dwell time ≥5 years performed at our tertiary centre were retrospectively analysed. A total of 173 leads, from 78 patients (median age 68 years; 81% male) with a median dwell time of 9 years (interquartile range [IQR] 5) were extracted, with three or more leads in 42% of the patients. Right atrial leads: 41%; right ventricular pacing leads: 16%; implantable cardioverter-defibrillator (ICD) leads: 31% (72% dual coil); coronary sinus leads: 12%. The majority (75%) of the leads had an active fixation. Most frequent indication for extraction was pocket infection/erosion (76%). Overall clinical success was 97%, and complete procedural success was 93%. Venous patency, assessed with venous angiography, was well preserved in 93% of the cases. The overall procedural complication rate was 3.8% (2.6% major and 1.3% minor). Despite the complexity of the population and a very long dwell time (median 9 years), a clinical success rate of 97% was achieved with the stepwise mechanical approach. Analysis of impeding progression of pectoral extraction suggests that dense fibrosis and sharp lead curvature in the transvenous trajectory pose a challenge. Complication rate was low, and acute venous patency was generally well preserved.

The impact of transvenous cardioverter-defibrillator implantation on quality of life, depression and optimism in dialysis patients: report on the secondary outcome of QOL in the randomized controlled ICD2 trial.

RATIONALE: The impact of prophylactic implantable cardioverter-defibrillator (ICD) implantation on the psychological well-being of patients on dialysis is unknown. OBJECTIVE: We aimed to identify the effect of primary ICD implantation on quality of life (QoL), mood and dispositional optimism in patients undergoing dialysis. METHODS AND RESULTS: We performed a prespecified subanalysis of the randomized controlled ICD2 trial. In total, 177 patients on chronic dialysis, with an age of 55-81 years, and a left ventricular ejection fraction of ≥ 35%, were included in the per-protocol analysis. Eighty patients received an ICD for primary prevention, and 91 patients received standard care. The Short Form-36 (SF-36), Geriatric Depression Scale-15 (GDS-15), Revised Life Orientation Test (LOT-R) questionnaires were administered prior to ICD implantation (T0), and at 1-year follow-up (T1) to assess QoL, depression and optimism, respectively. The patients were predominantly male (76.0%), with a median age of 67 years. Hemodialysis was the predominant mode of dialysis (70.2%). The GDS-15 score difference (T1 - T0) was 0.5 (2.1) in the ICD group compared with 0.3 (2.2) in the control group (mean difference - 0.3; 95% CI - 1.1 to 0.6; P = 0.58). The LOT-R score difference was - 0.2 (4.1) in the ICD group compared with - 1.5 (4.0) in the control group (mean difference - 1.1 (0.8); 95% CI - 2.6 to 0.4; P = 0.17). The mean difference scores of all subscales of the SF-36 were not significantly different between randomization groups. CONCLUSIONS: In our population of patients on dialysis, ICD implantation did not affect QoL, mood or dispositional optimism significantly during 1-year follow-up. CLINICAL TRIAL REGISTRATION: Unique identifier: ISRCTN20479861. http://www.controlled-trials.com .

Identification of known and unknown genes associated with mitral valve prolapse using an exome slice methodology.

PURPOSE: Although a familial distribution has been documented, the genetic aetiology of mitral valve prolapse (MVP) is largely unknown, with only four genes identified so far: FLNA, DCHS1, DZIP1 and PLD1. The aim of this study was to evaluate the genetic yield in known causative genes and to identify possible novel genes associated with MVP using a heart gene panel based on exome sequencing. METHODS: Patients with MVP were referred for genetic counselling when a positive family history for MVP was reported and/or Barlow's disease was diagnosed. In total, 101 probands were included to identify potentially pathogenic variants in a set of 522 genes associated with cardiac development and/or diseases. RESULTS: 97 (96%) probands were classified as Barlow's disease and 4 (4%) as fibroelastic deficiency. Only one patient (1%) had a likely pathogenic variant in the known causative genes (DCHS1). However, an interesting finding was that 10 probands (11%) had a variant that was classified as likely pathogenic in six different, mostly cardiomyopathy genes: DSP (1×), HCN4 (1×), MYH6 (1×), TMEM67 (1×), TRPS1 (1×) and TTN (5×). CONCLUSION: Exome slice sequencing analysis performed in MVP probands reveals a low genetic yield in known causative genes but may expand the cardiac phenotype of other genes. This study suggests for the first time that also genes related to cardiomyopathy may be associated with MVP. This highlights the importance to screen these patients and their family for the presence of arrhythmias and of 'disproportionate' LV remodelling as compared with the severity of mitral regurgitation, unravelling a possible coexistent cardiomyopathy.

Human epicardium-derived cells reinforce cardiac sympathetic innervation.

RATIONALE: After cardiac damage, excessive neurite outgrowth (sympathetic hyperinnervation) can occur, which is related to ventricular arrhythmias/sudden cardiac death. Post-damage reactivation of epicardium causes epicardium-derived cells (EPDCs) to acquire a mesenchymal character, contributing to cardiac regeneration. Whether EPDCs also contribute to cardiac re/hyperinnervation, is unknown. AIM: To investigate whether mesenchymal EPDCs influence cardiac sympathetic innervation. METHODS AND RESULTS: Sympathetic ganglia were co-cultured with mesenchymal EPDCs and/or myocardium, and neurite outgrowth and sprouting density were assessed. Results showed a significant increase in neurite density and directional (i.e. towards myocardium) outgrowth when ganglia were co-cultured with a combination of EPDCs and myocardium, as compared to cultures with EPDCs or myocardium alone. In absence of myocardium, this outgrowth was not directional. Neurite differentiation of PC12 cells in conditioned medium confirmed these results via a paracrine effect, in accordance with expression of neurotrophic factors in myocardial explants co-cultured with EPDCs. Of interest, EPDCs increased the expression of nerve growth factor (NGF) in cultured, but not in fresh myocardium, possibly due to an "ischemic state" of cultured myocardium, supported by TUNEL and Hif1α expression. Cardiac tissues after myocardial infarction showed robust NGF expression in the infarcted, but not remote area. CONCLUSION: Neurite outgrowth and density increases significantly in the presence of EPDCs by a paracrine effect, indicating a new role for EPDCs in the occurrence of sympathetic re/hyperinnervation after cardiac damage.

Prophylactic Use of Implantable Cardioverter-Defibrillators in the Prevention of Sudden Cardiac Death in Dialysis Patients.

BACKGROUND: Patients with end-stage renal disease who are undergoing dialysis are reported to be at high risk of sudden cardiac death (SCD), and to date, no therapy has been shown to be effective in reducing this risk. The feasibility and value of prophylactic implantable cardioverter-defibrillator (ICD) implantation to prevent SCD is uncertain. METHODS: We conducted the ICD2 trial (Implantable Cardioverter-Defibrillator in Dialysis Patients), a prospective, randomized, controlled study investigating the value and safety of ICD implantation to prevent SCD in 200 patients on dialysis with a left ventricular ejection fraction ≥35%, after adequate screening and optimization of other treatments. The primary end point was SCD. Secondary end points were all-cause mortality and ICD-related complications. RESULTS: The trial was stopped as per the recommendation of the data and safety monitoring board for futility reasons after inclusion of 188 patients, 97 in the ICD group and 91 in the control group. The median duration of follow-up was 6.8 years (interquartile range, 3.8-8.8 years). SCD occurred in 19 of 188 cases (10.1%), 11 of 97 in the ICD group and 8 of 91 in the control group. The cumulative SCD incidence at 5 years was 9.7% (95% CI, 3.3%-16.2%) in the ICD group and 7.9% (95% CI, 1.7-14.0%) in the control group, resulting in a hazard ratio of 1.32 (95% CI, 0.53-3.29; P=0.55). Overall, 99 of 188 patients died (52.7%), 52 in the ICD group and 47 in the control group. Five-year survival probability was 50.6% (95% CI, 39.8%-61.5%) in the ICD group and 54.5% (95% CI, 43.0-66.0%) in the control group, resulting in a hazard ratio of 1.02 (95% CI, 0.69-1.52; P=0.92). Among 80 patients who received an ICD, 25 adverse events related to ICD implantation occurred. CONCLUSIONS: In a well-screened and well-treated population undergoing dialysis, prophylactic ICD therapy did not reduce the rate of SCD or all-cause mortality, which remained high. CLINICAL TRIAL REGISTRATION: URL: http://www.controlled-trials.com . Unique identifier: ISRCTN20479861.

Procedural-related coronary atrial branch occlusion during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction and atrial arrhythmias at follow-up.

OBJECTIVES: To evaluate the frequency of procedural-related atrial branch occlusion in ST-segment elevation myocardial infarction (STEMI) patients and its association with atrial arrhythmias at 1-year follow-up. BACKGROUND: Atrial ischemia due to procedural-related coronary atrial branch occlusion in elective percutaneous coronary intervention (PCI) has been associated with atrial arrhythmias. Its role in a STEMI scenario is unknown. METHODS: STEMI patients treated with primary PCI were classified according to the loss or patency of an atrial branch at the end of the procedure. The occurrence of atrial arrhythmias was documented on 24-hr Holter-ECG at 3 and 6 months or on ECG during 1-year follow-up visits. RESULTS: Of 900 patients, 355 (age 61 ± 12 years, 79% male) underwent primary PCI involving the origin of an atrial branch. Procedural-related coronary atrial branch occlusion was observed in 18 (5%) individuals). During 1-year follow-up, 33% of patients with procedural-related atrial branch occlusion presented atrial arrhythmias, as compared with 55% in those with a patent atrial branch (p = .088). Age, no previous history of myocardial infarction, and a reduced flow in the culprit vessel were the only independent correlates of atrial arrhythmias. CONCLUSIONS: The frequency of procedural-related atrial branch occlusion during primary PCI is low (5%) and is not associated with increased frequency of atrial arrhythmias at 1-year follow-up.

An initial exploration of subtraction electrocardiography to detect myocardial ischemia in the prehospital setting.

BACKGROUND: In the prehospital triage of patients presenting with symptoms suggestive of acute myocardial ischemia, reliable myocardial ischemia detection in the electrocardiogram (ECG) is pivotal. Due to large interindividual variability and overlap between ischemic and nonischemic ECG-patterns, incorporation of a previous elective (reference) ECG may improve accuracy. The aim of the current study was to explore the potential value of serial ECG analysis using subtraction electrocardiography. METHODS: SUBTRACT is a multicenter retrospective observational study, including patients who were prehospitally evaluated for acute myocardial ischemia. For each patient, an elective previously recorded reference ECG was subtracted from the ambulance ECG. Patients were classified as myocardial ischemia cases or controls, based on the in-hospital diagnosis. The diagnostic performance of subtraction electrocardiography was tested using logistic regression of 28 variables describing the differences between the reference and ambulance ECGs. The Uni-G ECG Analysis Program was used for state-of-the-art single-ECG interpretation of the ambulance ECG. RESULTS: In 1,229 patients, the mean area-under-the-curve of subtraction electrocardiography was 0.80 (95%CI: 0.77-0.82). The performance of our new method was comparable to single-ECG analysis using the Uni-G algorithm: sensitivities were 66% versus 67% (p-value > .05), respectively; specificities were 80% versus 81% (p-value > .05), respectively. CONCLUSIONS: In our initial exploration, the diagnostic performance of subtraction electrocardiography for the detection of acute myocardial ischemia proved equal to that of state-of-the-art automated single-ECG analysis by the Uni-G algorithm. Possibly, refinement of both algorithms, or even integration of the two, could surpass current electrocardiographic myocardial ischemia detection.

Optimizing ablation duration using dormant conduction to reveal incomplete isolation with the second generation cryoballoon: A randomized controlled trial.

INTRODUCTION: Efficacy of cryoballoon ablation depends on balloon-tissue contact and ablation duration. Prolonged duration may increase extracardiac complications. The aim of this study is to determine the optimal additional ablation duration after acute pulmonary vein isolation (PVI). METHODS: Consecutive patients with paroxysmal AF were randomized to three groups according to additional ablation duration (90, 120, or 150 seconds) after acute PVI (time-to-isolation). Primary outcome was reconnection/dormant conduction (DC) after a 30 minutes waiting period. If present, additional 240 seconds ablations were performed. Ablations without time-to-isolation <90 seconds, esophageal temperature <18°C or decreased phrenic nerve capture were aborted. Patients were followed with 24-hour Holter monitoring at 3, 6, and 12 months. RESULTS: Seventy-five study patients (60 ± 11 years, 48 male) were included. Reconnection/DC per vein significantly decreased (22%, 6% and 4%) while aborted ablations remained stable (respectively 4, 5, and 7%) among the 90, 120, and 150 seconds groups. A shorter cryo-application time, longer time-to-isolation, higher balloon temperature and unsuccessful ablations predicted reconnection/DC. Freedom of atrial fibrillation was, respectively, 52, 56, and 72% in 90, 120, and 150 seconds groups ( P = 0.27), while repeated procedures significantly decreased from 36% to 4% ( P = 0.041) in the longer duration group compared to shorter duration group (150 seconds vs 90 seconds group). In multivariate Cox-regression only reconnection/DC predicted recurrence. CONCLUSION: Prolonging ablation duration after time-to-isolation significantly decreased reconnection/DC and repeated procedures, while recurrences and complications rates were similar. In a time-to-isolation approach, an additional ablation of 150 seconds ablation is the most appropriate.

Impact of left atrial box surface ratio on the recurrence after ablation for persistent atrial fibrillation.

BACKGROUND: The posterior wall of the left atrium (LA) is a well-known substrate for atrial fibrillation (AF) maintenance. Isolation of the posterior wall between the pulmonary veins (box lesion) may improve ablation success. Box lesion surface area size varies depending on the individual anatomy. This retrospective study evaluates the influence of box lesion surface area as a ratio of total LA surface area (box surface ratio) on arrhythmia recurrence. METHODS: Seventy consecutive patients with persistent AF (63 ± 11 years, 53 men) undergoing computed tomography (CT) imaging and ablation procedure consisting of a first box lesion were included in this study. Box lesion surface area was measured on electroanatomical maps and total LA surface area was derived from CT. Patients were followed with 24-h electrocardiography and exercise tests at 3, 6, and 12 months after AF ablation. Arrhythmia recurrence was defined as any AF/atrial tachycardia (AT) beyond 3 months without antiarrhythmic drugs. RESULTS: During a median follow-up of 13 (interquartile range = 10-17) months, 42 (60%) patients had AF/AT recurrence. Multivariate Cox proportional regression analysis showed that a larger box surface ratio protected against recurrence (hazard ratio [HR] = 0.81; 95% confidence interval [CI] = 0.690-0.955; P = 0.012). Left atrial volume index (HR = 1.01 [0.990-1.024, P = 0.427] and a history of mitral valve surgery (HR = 2.90; 95% CI = 0.970-8.693; P = 0.057) were not associated with AF recurrence in multivariate analysis. CONCLUSION: A larger box lesion surface area as a ratio of total LA surface area is protective for AF/AT recurrence after ablation for persistent AF.

Vasoplegia After Restrictive Mitral Annuloplasty for Functional Mitral Regurgitation in Patients With Heart Failure.

OBJECTIVES: Patients undergoing heart failure surgery are at risk for developing postoperative vasoplegia. The aim of this study was to determine the incidence, survival, and predictors of vasoplegia in heart failure patients undergoing mitral valve repair for functional mitral regurgitation and to evaluate the effect of ischemic versus non-ischemic etiology. DESIGN: Retrospective. SETTING: University medical center, single institutional. PARTICIPANTS: Heart failure patients with functional mitral regurgitation who underwent restrictive mitral annuloplasty (2006-2015). MEASUREMENTS AND MAIN RESULTS: One hundred twenty-two patients were included (48% ischemic etiology). The incidence of vasoplegia was 19% and was not influenced by mitral regurgitation etiology. Ninety-day survival rate was decreased in vasoplegic compared with non-vasoplegic patients (65% v 93%, p < 0.001). After adjusting for age, gender, and heart failure etiology, prior hypertension (odds ratio [OR] 0.28; 95% confidence interval [CI] 0.08-0.91; p = 0.034), higher creatinine clearance (OR 0.97; 95% CI 0.95-0.99; p = 0.009), and beta-blocker use (OR 0.25; 95% CI 0.09-0.73; p = 0.011) decreased the risk of vasoplegia. Anemia (OR 3.00; 95% CI 1.10-8.20; p = 0.032) and longer cross clamp (OR 1.03; 95% CI 1.01-1.04; p = 0.001), cardiopulmonary bypass (OR 1.01; 95% CI 1.00-1.02; p = 0.003), and procedure times (OR 1.01; 95% CI 1.00-1.02, p = 0.002) increased the risk of vasoplegia. CONCLUSIONS: Vasoplegia occurs in 19% of heart failure patients undergoing mitral valve repair for functional mitral regurgitation. It is associated with a poor early outcome. Prior hypertension, a higher creatinine clearance, and beta-blocker use were associated with a decreased risk of vasoplegia, whereas anemia and longer procedure times were associated with an increased risk of vasoplegia, independent of heart failure etiology.

Mortality differences in acute myocardial infarction patients in the Netherlands: The weekend-effect.

Objective: Several studies have shown that patients admitted with an acute myocardial infarction during the weekends have a higher mortality rate than those admitted during weekdays, possibly attributable to less trained personnel available and a lower use of medical procedures. The current study aimed to assess this 'weekend-effect' in a nationwide registry. Methods: In the Netherlands, all inhabitants are, by law, obliged to have health insurance and all claim data are centrally registered. In 2012 and 2013, all national diagnose-codings of STEMI and NSTEMI patients were acquired. One-year mortality rates and treatment with percutaneous coronary intervention (PCI) were compared between weekdays and weekends (holidays included). Results: In total, 59,534 patients (67 ± 13 years, 39,545(66%) male) were included of whom 33,904(57%) had a NSTEMI. Overall 6857(12%) patients died in the year following the acute myocardial infarction registration. In STEMI patients, no differences in one-year mortality rates were observed between admission on weekdays or weekends. In NSTEMI patients, one-year mortality was higher in those admitted during weekends (weekdays 11% versus weekends 13%, P < .001). Furthermore, STEMI patients admitted during weekends were more often treated with PCI (weekdays 77% versus weekends 81%, P < .001). Conversely, NSTEMI patients admitted during weekends were less often treated with PCI (weekdays 35% versus weekends 32%, P < .001). Conclusion: Differences in treatment and mortality rates exist between acute myocardial infarction patients admitted during weekdays and weekends. NSTEMI patients admitted during weekends are less often treated with PCI and have a higher mortality rate than patients admitted during weekdays.

Effects of Transcatheter Mitral Valve Repair With MitraClip on Left Ventricular and Atrial Hemodynamic Load and Myocardial Wall Stress.

AIMS: To evaluate the effects of MitraClip on left ventricular (LV) and left atrial (LA) myocardial wall stress as assessed with the use of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and strain imaging. METHODS AND RESULTS: Sixty-five patients with symptomatic moderate and severe mitral regurgitation (MR; age 75 ± 9 y, 57% male, 89% functional MR) treated with the use of MitraClip were evaluated. Patients were divided according to 6-month NT-proBNP tertiles. Changes in echocardiographic parameters over 6 months were assessed. Reductions in LV end-diastolic volumes (178 ± 77 mL to 170 ± 79 mL; P = .045) and LV end-systolic volumes (120 ± 70 mL to 111 ± 69 mL; P = .040) were observed in the overall population. Interestingly, low-NT-proBNP-tertile patients showed slight improvements in LV and LA longitudinal strain, whereas high-NT-proBNP-tertile patients showed impairment. CONCLUSIONS: Although MitraClip induces hemodynamic unloading in patients with predominantly functional MR, myocardial wall stress is not consistently improved. In patients with reduced NT-proBNP, improvements in LA volume index and LV and LA strains were observed. Patients who showed an increase in NT-proBNP exhibited impairment in LV and LA strain, suggesting an increase of myocardial wall stress.

Pulmonary Valve Morphology in Patients with Bicuspid Aortic Valves.

The aortic and pulmonary valve share a common developmental origin from the embryonic arterial trunk. Bicuspid aortic valve is the most common congenital anomaly and can occur isolated as well as in association with other congenital heart disease (CHD). Data on pulmonary valve morphology in these cases are scarce. In this study, we aimed to determine pulmonary valve morphology in hearts with BAV associated with CHD. In 83 post-mortem heart specimens with BAV and associated CHD, pulmonary valve morphology was studied and related to BAV morphology. In 14/83 (17%) hearts, the pulmonary valve was affected, bicuspid in 8/83 (10%), dome-shaped in 3/83 (4%) and atretic in 3/83 (4%). In specimens with a bicuspid pulmonary valve, 5/8 (63%) had a strictly bicuspid aortic valve (without raphe), 2/3 hearts (67%) with dome-shaped pulmonary valves and 2/3 hearts (67%) with atretic pulmonary valves had BAV without raphe. Six out of eight (75%) specimens with a bicuspid pulmonary valve had a perimembranous ventricular septal defect (VSD). 4/8 (50%) specimens with a bicuspid pulmonary valve were associated with chromosomal abnormalities: 3 (38%) had trisomy 18 and 1 (13%) had trisomy 13. In BAV with associated CHD, abnormal pulmonary valve morphology was observed in 17% of the hearts. The majority of hearts with abnormal pulmonary valve morphology had a Type B bicuspid aortic valve (without raphe). Bilateral semilunar valvular disease is associated with Type B BAVs and in many cases related to chromosomal abnormalities. As this study was performed in post-mortem specimens with high frequency of associated CHD, caution is warranted with application of these results to the general BAV population.