Safety of in-hospital insertable cardiac monitor procedures performed outside the traditional settings: results from the Reveal LINQ in-office 2 international study.

BACKGROUND: Historically, the majority of insertable cardiac monitor (ICM) procedures were performed in the cardiac catheterization (cath) lab, electrophysiology (EP) lab, or operating room (OR). The miniaturization of ICMs allows the procedure to be relocated within the hospital without compromising patient safety. We sought to estimate the rate of untoward events associated with procedures performed within the hospital but outside the traditional settings and to characterize resource utilization, procedure time intervals, and physician experience. METHODS: The Reveal LINQ in-Office 2 (RIO 2) International study was a single arm, multicenter, prospective study. Patients indicated for an ICM and willing to undergo device insertion outside the cath/EP lab or OR were eligible and followed for 90 days after insertion. RESULTS: A total of 191 patients (45.5% female aged 63.8 ± 26.9 years) underwent successful Reveal LINQ ICM insertion at 17 centers in Europe, Canada and Australia. The median total visit duration was 106 min (interquartile range [IQR]: 55-61). Patient preparation and patient education accounted for 10 min (IQR: 5-20) and 10 min (IQR: 8-15) of total visit duration, respectively. Preparation and education occurred in the procedure room for 90.6 and 60.2% of patients, respectively. There were no untoward events (0.0, 95% CI: 0.0-2.1%) though four patients presented with procedure-related adverse events that did not require invasive intervention. Physicians rated procedure location as convenient or very convenient. CONCLUSIONS: The Reveal LINQ™ ICM insertion can be safely and efficiently performed in the hospital outside the cath/EP lab or OR. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02412488 ; registered on April 9, 2015.

Intermediate and nonclassical monocytes show heterogeneity in patients with different types of acute coronary syndrome.

This study was performed to gain further insight in the heterogeneity of monocytes in the different categories of acute coronary syndrome (ACS), especially between patients with unstable angina pectoris, ST-elevation myocardial infarction (STEMI), and non-ST-elevation myocardial infarction (NSTEMI). For this purpose, blood samples were collected in the acute phase from patients presenting with an ACS. These samples were examined with multiparameter flow cytometry to identify the different monocyte subsets and to analyze the expression of monocyte-associated molecules. Leukocytes, as well as an absolute number of monocytes, showed a clear and significant increase in patients with STEMI. This increase was seen in all subtypes of monocytes. The classical monocytes (CD14++CD16-) of patients with an NSTEMI had a significantly increased CD11b expression when compared to the control group, while these cells showed a decreased expression pattern in STEMI patients. This increased CD11b-expression was also seen in the intermediate monocytes of NSTEMI, while it was almost completely downregulated on the intermediate monocytes of STEMI. Finally, CX3CR1, which is almost exclusively expressed on intermediate and nonclassical monocytes, showed a significant decrease in expression in patients with STEMI. In conclusion, intermediate and nonclassical monocytes have a different immunophenotypic pattern in patients with STEMI versus NSTEMI. These differences reflect the pro-inflammatory state of the monocytes in NSTEMI and can be used as target molecules for novel therapeutic strategies to diminish the migration of proinflammatory monocytes into the myocardial tissue. © 2017 International Society for Advancement of Cytometry.

Acute heart failure and iron deficiency: a prospective, multicentre, observational study.

AIMS: The prevalence and the natural course of iron deficiency (ID) in acute heart failure (AHF) are still unclear. We investigated the prevalence of ID in unselected patients admitted with AHF on admission, at discharge and up to 3 months thereafter. METHODS AND RESULTS: In this prospective, multicentre, observational study, 742 patients admitted with AHF were enrolled. The main study outcome was the percentage of patients with ID (ferritin <100 µg/L = absolute ID or ferritin 100-299 µg/L and transferrin saturation <20% = functional ID) at admission (T0), after clinical stabilization prior to discharge (T1), and 10 ± 6 weeks after discharge (T2). At T0, ID was present in 71.8% of the patients (44.1% absolute and 27.7% functional ID). At T1 and T2, ID was present in 56.4% (32.4% absolute and 24% functional ID) and 50.3% (36.8% absolute and 13.5% functional ID), respectively. Absolute ID persisted from T0 to T2 in 66% of the patients, while functional ID resolved in 56% of the patients. Ferritin (median [interquartile range] 124 µg/L [56-247] to 150 µg/L [73-277]), transferrin saturation (15% [10-20] to 18% [12-27]), and iron levels (9 µmol/L [6-13] to 11 µmol/L [8-16]) increased significantly (all P < 0.001) from T0 to T1. Transferrin saturation (to 21% [15-29]) and iron levels (to 13 µmol/L [9-17]) also increased significantly (both P < 0.01) from T1 to T2 without iron supplementation. CONCLUSIONS: Iron deficiency is highly prevalent in patients with AHF, but resolves during treatment in some patients, even without iron supplementation. Absolute ID is more likely to persist over time, whereas functional ID often resolves during treatment of AHF, representing probably a reduced iron availability rather than a true deficiency.

Does the use of locking plates or mesh and wires influence the risk of symptomatic non-union of the sternal osteotomy after modified Ravitch?

BACKGROUND: Patients with pectus excavatum which is unsuitable for minimally invasive repair are usually treated by modified Ravitch procedure. For fixation of the sternal osteotomy, mesh and wires are mostly used. To decrease non-union risk, we introduced a technique with double locking plate fixation of the osteotomy and compared this to fixation using mesh and wires. METHODS: Patients undergoing a modified Ravitch procedure for pectus excavatum between 2006 and 2016 were included. From 2006 to 2012, the sternum was fixated with mesh and wires. From 2012 to 2016, locking compression plates (LCP) were used. Baseline parameters, symptomatic non-union and total number of complications were retrospectively compared. Statistical analysis was performed using Mann-Whitney or Fisher's exact test. Data are presented as means +/- SD. RESULTS: Forty-four patients were included. In 18 patients, the sternum was fixed with mesh and wires, in 26 patients with LCP. Mean follow-up was 35 months in the mesh and 30 months in the LCP group, P=0.71. Haller index was similar in both groups (mesh 3.8±1.3 vs. LCP 3.9±1.1, P=0.81). Symptomatic non-union occurred in 17% (n=3) in the mesh group and did not occur after LCP, P=0.062. Total number of complications was 33% (n=6) in the mesh group and 15% (n=4) after LCP, P=0.27. CONCLUSIONS: After modified Ravitch procedure, union of the sternal osteotomy is challenging. In this retrospective cohort study, a lower incidence of symptomatic non-union was observed after fixation of the sternum with LCPs, with a trend towards statistical significance.

Anaemia and renal dysfunction are independently associated with BNP and NT-proBNP levels in patients with heart failure.

BACKGROUND: Anaemia may affect B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) levels, but this has not been well described in heart failure (HF) patients without the exclusion of patients with renal dysfunction. AIMS: To study the influence of both anaemia and renal function on BNP and NT-proBNP levels in a large group of hospitalised HF patients. METHODS AND RESULTS: We studied 541 patients hospitalised for HF (mean age 71+/-11 years, 62% male, and left ventricular ejection fraction 0.33+/-0.14). Of these patients, 30% (n=159) were anaemic (women: Hb<7.5 mmol/l, men: Hb<8.1 mmol/l). Of the 159 anaemic patients, 73% had renal dysfunction (eGFR<60 ml/min/1.73 m2) and of the non-anaemic patients, 57% had renal dysfunction. BNP and NT-proBNP levels were measured in all patients before discharge. In multivariable analyses both plasma haemoglobin and eGFR were independently related to the levels of BNP and NT-proBNP (standardised beta's of -0.16, -0.14 [BNP] and -0.19, -0.26 [NT-proBNP] respectively, P-values<0.01). CONCLUSION: Anaemia and renal dysfunction are related to increased BNP and NT-proBNP levels, independent of the severity of HF. These results indicate that both anaemia and renal dysfunction should be taken into consideration during the interpretation of BNP and NT-proBNP levels in HF patients.

Factor XIa and Thrombin Generation Are Elevated in Patients with Acute Coronary Syndrome and Predict Recurrent Cardiovascular Events.

OBJECTIVE: In acute coronary syndrome (ACS) cardiac cell damage is preceded by thrombosis. Therefore, plasma coagulation markers may have additional diagnostic relevance in ACS. By using novel coagulation assays this study aims to gain more insight into the relationship between the coagulation system and ACS. METHODS: We measured plasma thrombin generation, factor XIa and D-dimer levels in plasma from ACS (n = 104) and non-ACS patients (n = 42). Follow-up measurements (n = 73) were performed at 1 and 6 months. Associations between coagulation markers and recurrent cardiovascular events were calculated by logistic regression analysis. RESULTS: Thrombin generation was significantly enhanced in ACS compared to non-ACS patients: peak height 148±53 vs. 122±42 nM. There was a significantly diminished ETP reduction (32 vs. 41%) and increased intrinsic coagulation activation (25 vs. 7%) in ACS compared to non-ACS patients. Furthermore, compared to non-ACS patients factor XIa and D-dimer levels were significantly elevated in ACS patients: 1.9±1.1 vs. 1.4±0.7 pM and 495(310-885) vs. 380(235-540) µg/L. Within the ACS spectrum, ST-elevated myocardial infarction patients had the highest prothrombotic profile. During the acute event, thrombin generation was significantly increased compared to 1 and 6 months afterwards: peak height 145±52 vs. 100±44 vs. 98±33 nM. Both peak height and factor XIa levels on admission predicted recurrent cardiovascular events (OR: 4.9 [95%CI 1.2-20.9] and 4.5 [1.1-18.9]). CONCLUSION: ACS patients had an enhanced prothrombotic profile, demonstrated by an increased thrombin generation potential, factor XIa and D-dimer levels. This study is the first to demonstrate the positive association between factor XIa, thrombin generation and recurrent cardiovascular events.

Effect of long-acting nifedipine on mortality and cardiovascular morbidity in patients with stable angina requiring treatment (ACTION trial): randomised controlled trial.

BACKGROUND: Calcium antagonists are widely prescribed for angina pectoris but their effect on clinical outcome is controversial. We aimed to investigate the effect of the calcium antagonist nifedipine on long-term outcome in patients with stable angina pectoris. METHODS: We randomly assigned 3825 patients with treated stable symptomatic coronary disease to double-blind addition of nifedipine GITS (gastrointestinal therapeutic system) 60 mg once daily and 3840 to placebo. The primary endpoint was the combination of death, acute myocardial infarction, refractory angina, new overt heart failure, debilitating stroke, and peripheral revascularisation. Mean follow-up was 4.9 years (SD 1.1). Analysis was by intention to treat. FINDINGS: 310 patients allocated nifedipine died (1.64 per 100 patient-years) compared with 291 people allocated placebo (1.53 per 100 patient-years; hazard ratio 1.07 [95% CI 0.91-1.25], p=0.41). Primary endpoint rates were 4.60 per 100 patient-years for nifedipine and 4.75 per 100 patient-years for placebo (0.97 [0.88-1.07], p=0.54). With nifedipine, rate of death and any cardiovascular event or procedure was 9.32 per 100 patient-years versus 10.50 per 100 patient-years for placebo (0.89 [0.83-0.95], p=0.0012). The difference was mainly attributable to a reduction in the need for coronary angiography and interventions in patients assigned nifedipine, despite an increase in peripheral revascularisation. Nifedipine had no effect on the rate of myocardial infarction. INTERPRETATION: Addition of nifedipine GITS to conventional treatment of angina pectoris has no effect on major cardiovascular event-free survival. Nifedipine GITS is safe and reduces the need for coronary angiography and interventions.

The pro- and anticoagulant role of blood-borne phagocytes in patients with acute coronary syndrome.

This study was performed to gain further insight in pro- and anticoagulant characteristics of leukocytes in acute coronary syndrome (ACS). For this purpose, patients presenting on the emergency department (ED) with anginal chest pain were included in this study. In peripheral blood, procoagulant tissue factor (TF) expression was measured in the different blood-borne phagocytes, i.e. neutrophilic granulocytes and the three different monocyte subsets based on expression of CD14 and CD16. Simultaneously, intracellular presence of platelet-(CD41) and/or endothelial cell-remnants (CD62e) was analysed in these different leukocyte subsets. Neutrophils showed a weak intracellular staining of CD62e and CD41 that increased with severity of ACS. Monocytes, and especially the classical (CD14++CD16-) and intermediate monocytes (CD14++CD16+) showed a clear and significant increase in intracellular CD41-staining after coronary damage. The different monocyte subsets showed an increase in expression of TF in severe ACS. Finally, it appeared that also neutrophils showed a significant increase in expression of TF on their membrane. In conclusion, this study showed an increased intracellular staining in blood-borne phagocytes for CD62e and CD41 in patients with ACS compared to non-cardiac related control patients. This indicates that at least in the acute phase of ACS phagocytosis of platelet and endothelial cell-remnants is increased. These data support the recent hypothesis that neutrophils protect against further thrombotic processes by clearing platelet and endothelial cell-remnants. In addition, this study shows that the different monocyte subsets are also involved in this process. Furthermore, both monocytes and neutrophils show increased TF expression in ACS.

Patients originally diagnosed with idiopathic atrial fibrillation more often suffer from insidious coronary artery disease compared to healthy sinus rhythm controls.

BACKGROUND: Idiopathic atrial fibrillation (AF) refers to a clinically lacking cardiovascular or pulmonary disease generating the pathophysiologic substrate for the arrhythmia. However, because idiopathic AF is associated with an increased event rate, it could be a harbinger of as-yet undetected underlying heart disease. OBJECTIVE: The purpose of this study was to determine the prevalence of coronary artery disease (CAD) in patients diagnosed with idiopathic paroxysmal AF. METHODS: Of the 3243 patients who underwent cardiac computed tomographic angiography (CTA) in our center between January 2008 and March 2011, we identified a total of 115 consecutive idiopathic paroxysmal AF patients who underwent CTA before electrophysiologic ablation. Patients were compared with 275 age-, sex-, and PROCAM risk score-matched healthy controls in permanent sinus rhythm. All patients were free of hypertension, diabetes, congestive heart failure, previous known coronary artery and peripheral vascular disease, previous stroke, thyroid, pulmonary, and renal disease, and structural abnormalities on echocardiography. RESULTS: Controls more often showed a family history of CAD (38% vs 15%, P <.001), had a higher prevalence of smoking (25% vs 14%, P = .021), higher fasting blood glucose levels (5.5 ± 0.7 mmol/L vs 5.4 ± 0.6 mmol/L, P = .025), and smaller atrial diameters (37 ± 4 mm vs 40 ± 5 mm, P <.001) compared to AF patients. Notwithstanding the above, idiopathic AF patients significantly more often suffered from subclinical CAD compared to controls (49% vs 34%, P = .008). Multivariable regression analysis revealed that beside (as expected) age and gender, a history of AF and left atrial diameter were significant predictors of underlying CAD. CONCLUSION: Half of patients originally diagnosed with idiopathic paroxysmal AF show concealed underlying CAD. The detection and treatment of CAD at an early stage could improve the prognosis of these patients.

Nifedipine Gastrointestinal Therapeutic System (GITS) in the treatment of coronary heart disease and hypertension.

Since the 1960s, calcium antagonists have been available for the treatment of angina pectoris and hypertension. The first of this class, nifedipine, was introduced and readily accepted as the third treatment option for angina, alongside beta-blockers and nitrates. However, the short-acting formulations of nifedipine had pharmacokinetic properties that were far from ideal and in 1995, several studies involving various dosing regimens reported possible dangerous effects in secondary prevention. Since then, large-scale, randomized controlled trials with new controlled-released formulations of nifedipine have demonstrated the effectiveness and safety of this drug. As a consequence of these results, guidelines for both hypertension and angina pectoris have been recently reconsidered, and have put the modern formulations of calcium channel blockers in a pole position. Within this group of therapeutics, nifedipine gastrointestinal therapeutic system has a unique position and it cannot be replaced by other controlled-release formulations of nifedipine, the pharmaceutical properties of which have yet to be tested in large-scale outcome trials.