One-year mortality in NSTEMI patients is unaffected by timing of PCI within the first week of admission: Results of a real-world cohort analysis.

OBJECTIVES: We aimed to explore the impact of time to percutaneous coronary intervention (PCI) (T2P) on 1-year mortality in non-ST-elevation myocardial infarction (NSTEMI) patients. BACKGROUND: The current guidelines recommend an early invasive strategy for NSTEMI patients. However, impact of an early invasive strategy on mortality is a matter of debate. For that reason, real world data are of great value to determine the optimal treatment window. METHODS: This retrospective single center cohort study was performed in a high-volume PCI center in Amsterdam, The Netherlands. Intermediate- and high-risk NSTEMI patients undergoing PCI were included. The main discriminant was timing of PCI after admission (T2P), stratified according to different time windows (<24 h, 24-72 h, 72 h-7 days or >7 days). We analyzed 1-year mortality and the time distribution of overall survival. RESULTS: In total, 848 patients treated between January 1, 2016 and January 1, 2018 were included in the analysis. T2P was <24 h in 145 patients, 24-72 h in 192 patients, 72 h-7 days in 275 patients, and >7 days in 236 patients. The mean GRACE-risk score was 127.1 (SD 28.7), 130.0 (33.1), 133.8 (32.1), and 148.7 (34.6) respectively, p = <0.001. After adjusting for confounders, 1-year mortality in patients with T2P <24 h did not significantly differ when compared with T2P 24-72 h (OR = 1.08; 95% CI = 0.33-3.51) and T2P 72 h-7 days (OR 1.72; 95% CI = 0.57-5.21) but was significantly higher in T2P >7 days (OR = 3.20; 95% CI = 1.06-9.68). CONCLUSIONS: In an unselected cohort of patients with NSTEMI, treatment by PCI <24 h did not lead to improved survival as compared to aT2P <7 days strategy. Delay in PCI >7 days after admission resulted in worse outcome.

Elderly patients benefit from minimally invasive mitral valve surgery: perioperative risk management matters.

OBJECTIVES: The goal was to assess the single-centre results of minimally invasive mitral valve surgery (MIMVS) in the elderly population. METHODS: All patients referred for minimally invasive valve surgery underwent a standardized preoperative screening. We performed a retrospective analysis of 131 consecutive elderly patients (≥75 years) who underwent endoscopic MIMVS through a right mini-thoracotomy. Survival and postoperative course were assessed in 2 groups: a repair group and a replacement group. RESULTS: Eighty-five patients underwent mitral valve repair, and 46 had mitral valve replacement. The mean age was 79 ± 2.9 years, and the median follow-up duration was 3.8 years. The cardiopulmonary bypass time (128.7 min vs 155.9 min, P = 0.012) and the cross-clamp time (84.9 min vs 124.1 min, P = 0.005) were significantly longer in the replacement group. Except for more reinterventions for bleeding in the replacement group (10.9% vs 0%, P = 0.005), there were no significant differences in the postoperative course between the 2 groups. Low mortality rates at the midterm follow-up were observed in both groups, and no differences were observed between the 4-and the 12-month follow-up. Survival rates after 1 year and 5 years were 97.6% and 88.6%, respectively, with no significant differences between the 2 groups. CONCLUSIONS: MIMVS is an excellent treatment option in vulnerable elderly patients with excellent short- and long-term results. Although other studies suggest that repair could be superior to replacement even in older patients, our experience suggests that replacement is equivalent to repair in terms of mortality and major adverse cardiac and cerebrovascular events. Experience and standardized preoperative screening are mandatory to achieve optimal results.

Sex differences in characteristics of atrial fibrillation recurrence post surgical pulmonary vein isolation.

Background: Prior studies demonstrated that female sex is associated with arrhythmia recurrence after endovascular pulmonary vein isolation (PVI). However, it is unknown if the sexes differ in outcome after video assisted thoracoscopic (VATS) PVI. The aim of this study was therefore to compare characteristics of recurrent AF episodes in a matched male and female population, using implantable loop recorders for continuous rhythm monitoring. Methods: 40 matched (based on propensity score) males (age: 60.0 ± 7.71 (45-75)) and females (age: 62.0 ± 7.0 (37-74)) were retrieved from an existing database from a prior conducted study by the cardiothoracic department of the OLVG hospital (1) containing patients who received an implantable looprecorder and underwent a VATS PVI between 2012 and 2017. Patients were continuously monitored for a period of 12 months after VATS PVI and AF characteristics were compared. Results: An equal number of males and females had AF episodes during all periods (P > 0.05). The number of AF episodes was higher in females, during the first 6 months (P = 0.01, P = 0.034). During the entire follow up, the total AF duration was longer in females (P = 0.01, for all periods) with shorter inter - episode intervals (P = 0.001, P = 0001, P = 0.04) and a higher AF burden (P = 0.003, P = 0001, P = 0.006). After 3 months, AF recurrences during the night were more frequently observed in female patients (P = 0.001, P = 0.001). Conclusions: AF episodes occur frequently in both sexes after VATS PVI and warrant frequent rhythm monitoring. The observed sex differences in AF burden after VATS PVI, calls for intensive rhythm monitoring and aggressive treatment of recurrent AF epsiodes in females.

Do depressive and anxiety symptoms influence the quality of life of patients with atrial fibrillation after cryoballoon ablation: a comparison study.

BACKGROUND AND AIMS: One third of patients with atrial fibrillation (AF) suffer from high levels of anxiety and depression, which may significantly impair quality of life (QoL). The purpose of this study was to assess whether depressive and anxiety symptoms before ablation affect the QoL in patients with AF one year after cryoballoon ablation (CBA). METHODS: This single-center retrospective study investigated whether the AF patients with a high Hospital Anxiety and Depression Scale (HADS) score (≥ 8) had worse outcomes than patients with a low pre-ablation HADS score (< 8). The primary outcome was the difference in post-ablation QoL, and the secondary outcome included the difference in pre-ablative QoL, QoL improvement, and self-reported AF. RESULTS: Two hundred ninety-five patients were stratified according to their HADS scores (total, depression, and anxiety). Patients with an elevated HADS total, depression, or anxiety score (≥ 8), had a significantly lower QoL before and 12 months after CBA than patients with a HADS score < 8 (p-value < 0.001 for all groups). All groups improved significantly in QoL after CBA ablation and to a similar extent. Sixty-three percent of the patients reported AF symptoms after the procedure, which was comparable between the cohorts of patients. CONCLUSION: Patients with elevated HADS scores reported a lower QoL compared to participants with low HADS scores at baseline and 12 months after CBA. However, both groups improved in QoL after CBA, irrespective of their depressive and anxiety symptoms.

Essential Thrombocytosis in Patients <40 Years Old With Acute Coronary Syndromes: A Not So Uncommon Underlying Diagnosis Often Overlooked.

BACKGROUND: In patients under <40 years, traditional cardiovascular (CV)-risk factors are a less likely cause of acute coronary syndromes (ACS) compared to older counterparts. AIMS: To estimate the prevalence of essential thrombocytosis (ET), a hematological disorder and less-prevalent risk factor, in young patients presenting with ACS. METHODS: We constructed a retrospective database of all patients <40 years (n=271) that had consecutively undergone coronary angiography (CAG) after their first ACS within our hospital within the last ten years (2010-2020) and had known thrombocyte counts (n=241). Patients with thrombocytes >450x10*9/L were screened for this hematological disorder. RESULTS: In our database, we identified 15 subjects with thrombocytosis. One was previously known as ET. Of the remaining 14 patients, five were considered reactive/secondary thrombocytosis, and four were lost to follow-up, four were eventually diagnosed with ET, one remains uncertain. The diagnosis was newly established before the initiation of this study in two patients (average delay: six years). Two patients were identified as a result of this study.  Conclusion: With a prevalence of at least 2.1%, ET appears not uncommon in patients <40 years with ACS. Moreover, screening patients with ACS and elevated thrombocytes yielded a novel diagnosis of ET in 27% of patients. The diagnosis was initially missed in all cases. Since the timing of revascularization should be adjusted to thrombocyte count/initiation of ET therapy to prevent thrombotic complications, cardiologists should know, recognize and screen for this pathology in ACS-patients, notably in those with absent traditional CV-risk factors: an 'ACS-protocol' aimed at less-prevalent risk factors could support this.

Minimal invasive aortic valve replacement: associations of radiological assessments with procedure complexity.

OBJECTIVES: Limited aortic annulus exposure during minimal invasive aortic valve replacement (mini-AVR) proves to be challenging and contributes to procedure complexity, resulting in longer procedure times. New innovations like sutureless valves have been introduced to reduce procedure complexity. Additionally, preoperative imaging could also contribute to reducing procedure times. Therefore, we hypothesize that Computed Tomography (CT)-image based measurements are associated with mini-AVR complexity. METHODS: One hundred patients who underwent a mini-sternotomy and had a preoperative CT scan were included. With a CT-based mini-AVR planning tool, we measured access distance, access angle, annulus dimensions, and calcium volume. The associations of these measurements with cardiopulmonary bypass (CPB) time and aortic cross-clamp (AoX) time were assessed using univariable and multivariable regression models. In the multivariable models, these measurements were adjusted for age and suture technique. RESULTS: In the univariable regression models, calcium volume and annulus dimensions were associated with longer CPB and AoX time. After adjusting for age and suture technique, increasing calcium volume was still associated with longer CPB (adjusted ß-coefficient 0.002, 95%-CI (0.005, 0.019), p-value = 0.002) and AoX time (adjusted ß-coefficient 0.010, 95%-CI (0.004, 0.016), p-value = 0.002). However, after adjusting for these confounders, the association between annulus dimensions and procedure times lost statistical significance. CONCLUSION: Increase in calcium volume are associated with longer CPB and AoX times, with age and sutureless valve implantation as independent confounders. In contrast to previous studies, access angle was not associated with procedure complexity.

Resequencing three candidate genes for major depressive disorder in a Dutch cohort.

Major depressive disorder (MDD) is a psychiatric disorder, characterized by periods of low mood of more than two weeks, loss of interest in normally enjoyable activities and behavioral changes. MDD is a complex disorder and does not have a single genetic cause. In 2009 a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. Many of the top signals of this GWAS mapped to a region spanning the gene PCLO, and the non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became genome wide significant after post-hoc analysis. We performed resequencing of PCLO, GRM7, and SLC6A4 in 50 control samples from the GAIN-MDD cohort, to detect new genomic variants. Subsequently, we genotyped these variants in the entire GAIN-MDD cohort and performed association analysis to investigate if rs2522833 is the causal variant or simply in linkage disequilibrium with a more associated variant. GRM7 and SLC6A4 are both candidate genes for MDD from literature. We aimed to gather more evidence that rs2522833 is indeed the causal variant in the GAIN-MDD cohort or to find a previously undetected common variant in either PCLO, GRM7, or SLC6A4 with a higher association in this cohort. After next generation sequencing and association analysis we excluded the possibility of an undetected common variant to be more associated. For neither PCLO nor GRM7 we found a more associated variant. For SLC6A4, we found a new SNP that showed a lower P-value (P = 0.07) than in the GAIN-MDD GWAS (P = 0.09). However, no evidence for genome-wide significance was found. Although we did not take into account rare variants, we conclude that our results provide further support for the hypothesis that the non-synonymous coding SNP rs2522833 in the PCLO gene is indeed likely to be the causal variant in the GAIN-MDD cohort.

A fine-mapping study of 7 top scoring genes from a GWAS for major depressive disorder.

Major depressive disorder (MDD) is a psychiatric disorder that is characterized--amongst others--by persistent depressed mood, loss of interest and pleasure and psychomotor retardation. Environmental circumstances have proven to influence the aetiology of the disease, but MDD also has an estimated 40% heritability, probably with a polygenic background. In 2009, a genome wide association study (GWAS) was performed on the Dutch GAIN-MDD cohort. A non-synonymous coding single nucleotide polymorphism (SNP) rs2522833 in the PCLO gene became only nominally significant after post-hoc analysis with an Australian cohort which used similar ascertainment. The absence of genome-wide significance may be caused by low SNP coverage of genes. To increase SNP coverage to 100% for common variants (m.a.f.>0.1, r(2)>0.8), we selected seven genes from the GAIN-MDD GWAS: PCLO, GZMK, ANPEP, AFAP1L1, ST3GAL6, FGF14 and PTK2B. We genotyped 349 SNPs and obtained the lowest P-value for rs2715147 in PCLO at P = 6.8E-7. We imputed, filling in missing genotypes, after which rs2715147 and rs2715148 showed the lowest P-value at P = 1.2E-6. When we created a haplotype of these SNPs together with the non-synonymous coding SNP rs2522833, the P-value decreased to P = 9.9E-7 but was not genome wide significant. Although our study did not identify a more strongly associated variant, the results for PCLO suggest that the causal variant is in high LD with rs2715147, rs2715148 and rs2522833.

Opposite effects of early maternal deprivation on neurogenesis in male versus female rats.

BACKGROUND: Major depression is more prevalent in women than in men. The underlying neurobiological mechanisms are not well understood, but recent data shows that hippocampal volume reductions in depressed women occur only when depression is preceded by an early life stressor. This underlines the potential importance of early life stress, at least in women, for the vulnerability to develop depression. Perinatal stress exposure in rodents affects critical periods of brain development that persistently alter structural, emotional and neuroendocrine parameters in adult offspring. Moreover, stress inhibits adult hippocampal neurogenesis, a form of structural plasticity that has been implicated a.o. in antidepressant action and is highly abundant early postnatally. We here tested the hypothesis that early life stress differentially affects hippocampal structural plasticity in female versus male offspring. PRINCIPAL FINDINGS: We show that 24 h of maternal deprivation (MD) at PND3 affects hippocampal structural plasticity at PND21 in a sex-dependent manner. Neurogenesis was significantly increased in male but decreased in female offspring after MD. Since no other structural changes were found in granule cell layer volume, newborn cell survival or proliferation rate, astrocyte number or gliogenesis, this indicates that MD elicits specific changes in subsets of differentiating cells and differentially affects immature neurons. The MD induced sex-specific effects on neurogenesis cannot be explained by differences in maternal care. CONCLUSIONS: Our data shows that early environment has a critical influence on establishing sex differences in neural plasticity and supports the concept that the setpoint for neurogenesis may be determined during perinatal life. It is tempting to speculate that a reduced level of neurogenesis, secondary to early stress exposure, may contribute to maladaptation of the HPA axis and possibly to the increased vulnerability of women to stress-related disorders.