Parenteral Anticoagulation at First Medical Contact Improves Infarct Related Artery Patency in STEMI.

(1) Background: Acute ST-segment elevation myocardial infarction (STEMI) remains one of the main morbidity and mortality contributors worldwide. Its main treatment, primary percutaneous coronary intervention (pPCI), can only be performed with a high anticoagulation regimen, usually with heparin. There is still not enough evidence regarding the timing of heparin administration. (2) Methods: We conducted a multicenter observational study of 614 consecutive STEMI patients treated between 2017 and 2019. We split the population in two groups: one that received heparin at the first medical contact, as early as possible, and the second group that received heparin at the PCI capable center or in the cath lab. (3) Results: There was a significantly higher rate of infarct-related artery (IRA) patency at the time of the coronary angiogram in the pre-transfer heparin group than in the on-site heparin group, 44.7% vs. 37.3%, p = 0.042. Also, the early heparin group received shorter and wider stents. There was no difference in bleeding rates or in the in-hospital and two-year mortality rates. (4) Conclusions: Early administration of heparin leads to a higher rate of reperfusion in the IRA, before pPCI, with significant related benefits, such as better stent implantation parameters, without increased bleeding rates.

Left Ventricular-Arterial Coupling as an Independent Predictor of Adverse Events in Young Patients with ST Elevation Myocardial Infarction-A 3D Echocardiographic Study.

Left ventricular-arterial coupling (VAC) is a key determinant of global cardiovascular performance, calculated as the ratio between arterial elastance (EA) and left ventricular end-systolic elastance (EES). Over the years, acute myocardial infarction (STEMI) has remained an important cause of morbidity and mortality worldwide. Although, until recently, it was considered a disease occurring mostly in older patients, its prevalence in the young population is continuously rising. In this study, we aimed to investigate the role of 3D VAC and its derived indices in predicting adverse outcomes in young patients with STEMI. We prospectively enrolled 84 young patients (18-51 years) with STEMI who underwent primary PCI and 28 healthy age and sex-matched controls. A 3D echocardiography was used for non-invasive measurements of end-systolic elastance (EES), arterial elastance (EA), and VAC (EA/EES). The occurrence of major adverse cardiac events (MACE) was assessed one year after the index STEMI. Out of 84 patients, 15.4% had adverse events at 12 months follow-up. Patients were divided into two groups according to the presence or absence of MACE. There were no significant differences in arterial elastance between the two groups. EA was higher in the MACE group but without statistical significance (2.65 vs. 2.33; p = 0.09). EES was significantly lower in the MACE group (1.25 ± 0.34 vs. 1.91 ± 0.56. p < 0.0001) and VAC was higher (2.2 ± 0.62 vs. 1.24 ± 0.29, p < 0.0001). ROC analysis showed that VAC has a better predictive value for MACE (AUC 0.927) compared with EA or EEA but also compared with a classical determinant of LV function (LVEF and LVGLS). A VAC value over 1.71 predicts unfavourable outcome with 83.3% sensitivity and 97.1% specificity. In both univariate and multivariate COX regression analysis, VAC remained an independent predictor for MACE and demonstrated incremental prognostic value over LVEF and LVGLS in the proposed statistical models. In conclusion, 3D VAC is an independent predictor of adverse events in young patients with STEMI at a 12 month follow-ups and could be used for a more accurate risk stratification in the acute phase.

Left Atrial Low-Voltage Areas Predict the Risk of Atrial Fibrillation Recurrence after Radiofrequency Ablation.

Atrial fibrillation (AF), the most frequently encountered arrhythmia worldwide, is associated with increased cardiovascular morbidity and mortality. Left atrial (LA) and antral region of the pulmonary veins (PVs) remodeling are risk factors for AF perpetuation. Among the methods of LA fibrosis quantification, bipolar voltage mapping during three-dimensional electro-anatomical mapping is less studied. The main aim of this study was to analyze the relationship between the degree of LA fibrosis quantified in low-voltage areas and the efficacy of AF radiofrequency catheter ablation. All consecutive patients with AF ablation were included, and the degree of LA fibrosis was measured based on the low-voltage areas in the LA and the antral region of PVs (<0.5 mV for patients in sinus rhythm and <0.25 mV for patients in AF at the time of the ablation procedure). The efficacy of AF ablation was determined by the rate of recurrence after a blanking period of three months. A total of 106 patients were included; from these, 38 (35.8%) had AF recurrence after RF ablation, while 68 (64.2%) were free of events. The area and percentage of LA fibrosis were significantly higher in the patients with AF recurrence (p = 0.018 and p = 0.019, respectively). However, no significant differences were found between the patients with and without AF recurrence in terms of the area and percentage of PVs fibrosis (p = 0.896 and p = 0.888, respectively). Moreover, LA fibrosis parameters proved to be excellent predictors for AF recurrence (areas under the curve of 0.834 and 0.832, respectively, p < 0.001) even after adjustment for LA indexed volume and CHA2DS2-VASc score. In conclusion, LA fibrosis measured on bipolar voltage maps increases the risk of AF recurrence after the RF catheter ablation procedure.

Yield of Rare Variants Detected by Targeted Next-Generation Sequencing in a Cohort of Romanian Index Patients with Hypertrophic Cardiomyopathy.

BACKGROUND: The aim of this study was to explore the rare variants in a cohort of Romanian index cases with hypertrophic cardiomyopathy (HCM). METHODS: Forty-five unrelated probands with HCM were screened by targeted next generation sequencing (NGS) of 47 core and emerging genes connected with HCM. RESULTS: We identified 95 variants with allele frequency < 0.1% in population databases. MYBPC3 and TTN had the largest number of rare variants (17 variants each). A definite genetic etiology was found in 6 probands (13.3%), while inconclusive results due to either known or novel variants were established in 31 cases (68.9%). All disease-causing variants were detected in sarcomeric genes (MYBPC3 and MYH7 with two cases each, and one case in TNNI3 and TPM1 respectively). Multiple variants were detected in 27 subjects (60%), but no proband carried more than one causal variant. Of note, almost half of the rare variants were novel. CONCLUSIONS: Herein we reported for the first time the rare variants identified in core and putative genes associated with HCM in a cohort of Romanian unrelated adult patients. The clinical significance of most detected variants is yet to be established, additional studies based on segregation analysis being required for definite classification.

The Great Myocardial Mimic - Takotsubo Syndrome.

Takotsubo syndrome has been traditionally considered a reversible form of acute heart failure triggered by an emotional or physical stressor, mainly occurring in women of post-menopausal age and often mimicking an acute coronary syndrome. While its pathophysiology is still incompletely understood, sympathetic overstimulation is known to play a central role in the disease. The classical hallmark of the condition was the presence of wall motion abnormalities limited to the apical segments of the ventricle, leading to the so-called apical ballooning, but different patterns of wall motion abnormalities are nowadays recognised. Different definitions and diagnostic criteria for takotsubo syndrome were proposed during the last decades, reflecting the heterogeneity of the condition and the gaps in the thorough understanding of the disease. While initially it was believed to be a benign entity, takotsubo syndrome has in fact similar morbidity and mortality with acute coronary syndromes, both on short- and long-term, highlighting the importance of proper risk stratification. Many questions still remain unanswered concerning the pathophysiology of the syndrome and the optimal therapeutic strategy for these patients.

NT-proBNP and CA 125 levels are associated with increased pro-inflammatory cytokines in coronary sinus serum of patients with chronic heart failure.

PURPOSE: Heart failure (HF) is considered to be a complex syndrome associated with neurohormonal and cytokine activation, that contribute to its progression. There are evidences which showed that, carbohydrate antigen 125 (CA 125), a tumor marker widely used for ovarian cancer therapy monitoring, was significantly elevated in HF patients. We hypothesized that inflammatory stimuli may be responsible for amino-terminal fragment of the prohormone B-type natriuretic peptide (NT-proBNP) and CA-125 production and release in chronic HF (CHF). We aimed to measure the levels of NT-proBNP, CA 125, pro-anti-inflammatory cytokines (IL-6, IL-1ß, IL-8, TNF-α and IL-4), from peripheral venous (PV) and coronary sinus (CS) blood samples, in patients with CHF and to assess their correlation with echocardiographic indices. METHODS: We enrolled 32 subjects (20M/12F) with CHF (III-IV NYHA functional class) who were to undergo cardiac resynchronization therapy (CRT) device implantation and 30 healthy controls (18M/12F). Two blood samples, from PV and CS, were collected at the time of CRT for each CHF patient. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: All investigated biomarkers were significantly higher in CHF patients than in non-CHF controls (P < 0.001). There were positive correlations between biomarkers concentrations in PV and CS (r between 0.54 and 0.98, all P < 0.003). NT-proBNP, IL-6 and IL-1ß levels were 17%, 86% and 36% higher in CS than in PV, these increases being very well correlated each other, while CA 125 levels were 86% higher in PV than in CS. Moreover, CS NT-proBNP, CS IL-6 and CS IL-1ß serum concentrations were inversely related to the echocardiographically determined left ventricular ejection fraction (LVEF) (r = -0.61, P < 0.001; r = -0.71, P < 0.001 and r = -0.48, P = 0.005, respectively). A positive relationship was found between CA 125 and IL-1ß (r = 0.51, P = 0.003) in CS serum and between CA 125 and IL-6 (r = 0.43, P = 0.015), TNF-α (r = 0.46, P = 0.008) in PV serum. CA 125 concentrations were closely related to NT-proBNP both in CS (r = 0.46, P = 0.008) and PV (r = 0.52, P = 0.002). CONCLUSIONS: CS sampling of NT-proBNP, CA 125 and pro-anti-inflammatory cytokines provides an additional insight into the possible mechanisms by which these biomarkers lead to left ventricular remodeling. Our results clearly suggest that serum NT-proBNP and CA 125 levels not only in PV, but also in CS of patients with CHF, may be dependent on inflammation as a consequence of cytokine network activation.

The role of pro-fibrotic biomarkers in paroxysmal and persistent atrial fibrillation.

PURPOSE: Signaling pathways involved in electrical, structural and contractile remodeling processes behind development and progression of atrial fibrillation (AF) have not been completely elucidated, but it seems to be related to complex interactions among neurohormonal and cellular mediators. We aimed to investigate interleukin-6 (IL-6), transforming growth factor-beta1 (TGF-ß1), matrix metalloproteinase-9 (MMP-9), tissue inhibitor of metalloproteinase-1 (TIMP-1), as biomarkers of atrial remodeling, in patients with paroxysmal and persistent AF, and their correlation with N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and left atrial (LA) diameter. METHODS: Thirty-seven patients (22M/15F) with paroxysmal AF, 32 patients (22M/10F) with persistent AF and 30 healthy control subjects (18M/12F) were enrolled in the study. Serum levels of biomarkers were measured by ELISA. Cardiac function was assessed echocardiographically. RESULTS: IL-6 levels and MMP-9/TIMP-1 ratio were significantly higher in AF patients than in non-AF controls (P < .001), and in persistent than in paroxysmal AF (P < .001), in line with NT-proBNP and LA diameter. In contrast, TGF-ß1levels declined with increasing AF duration (from 51.2 pg/mL, IQR: 38.9-87.9 pg/mL in paroxysmal to 23.9 pg/mL, IQR: 16.9-43.6 pg/mL in persistent AF). TGF-ß1 was negatively correlated with NT-proBNP (r = -0.53, P = .001 in paroxysmal AF and r = -0.71, P < .001 in persistent AF) and LA diameter (r = -0.44, P = .006 in paroxysmal AF and r = -0.51, P = .003 in persistent AF). CONCLUSIONS: Our results demonstrate that AF development and progression (from paroxysmal to persistent) is associated with a gradual increase in serum levels of NT-proBNP, IL-6 and MMP-9/TIMP-1 ratio. Moreover, this study suggests that the relationship between TGF-ß1, NT-proBNP and LA diameter allows for the progression of atrial remodeling during AF, despite compensatory changes in the TGF-ß1 signaling pathway.

Cardiac resynchronization therapy in patients with chronic heart failure is associated with anti-inflammatory and anti-remodeling effects.

OBJECTIVES: Proinflammatory cytokines, matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a role in left ventricular (LV) structural remodeling. We aimed to investigate the effects of cardiac resynchronization therapy (CRT) on serum levels of amino-terminal prohormone B-type natriuretic peptide (NT-proBNP), some interleukins (IL-1ß, IL-6, IL-8), MMP-2 and TIMP-2 in patients with chronic heart failure (CHF). DESIGN AND METHODS: We studied 27 patients (15 M/12 F) with CHF, III-IV NYHA class, implanted with a biventricular pacemaker/defibrillator and 40 healthy subjects (23 M/17 F). Blood samples were collected at baseline and 1 week, 3, 6, and 12 months after CRT device implantation. Cardiac function was assessed echocardiographically. RESULTS: CRT induced significant improvement in the NYHA class (baseline 3.2±0.5 vs. 1.0 at 12 months, P=0.0002) and significant LV reverse remodeling, with a 41% (P=0.001) reduction in LV end-systolic volume (LVESV). This was associated with a significant reduction in serum NT-proBNP, IL-6 and IL-8. Positive extracellular matrix remodeling was illustrated by decreasing levels of MMP-2 and increasing TIMP-2. MMP-2/TIMP-2 ratio decreased with 55% (P=0.003) from baseline value at 12 months and the correlation with LVESV reduction was 0.41 (P=0.001). CONCLUSIONS: Structural response to CRT is associated with reduced immune activation and positive extracellular matrix remodeling.

Identical anatomical location of accessory pathway in a family with Wolff-Parkinson-White syndrome.

Identical location of accessory pathways in family members with Wolff-Parkinson-White syndrome, although theoretically possible, has never been described. A 37-year-old woman and her 18-year-old son were referred for electrophysiological study due to fast rate palpitations and pre-excitation on baseline electrocardiogram. After mapping during pre-excitation, successful radiofrequency application was located at the right free wall in both patients, in an identical anatomical position, on the infero-lateral aspect of the tricuspid ring.