The Optimal Management of Patients with Atrial Fibrillation and Acute Heart Failure in the Emergency Department.

Atrial fibrillation (AF) and acute heart failure (AHF) are two closely interrelated conditions that frequently coexist in a manifold manner, with AF serving either as the causative factor or as the consequence or even as an innocent bystander. The interplay between these two clinical conditions is complex, given that they share common pathophysiological pathways and they can reciprocally exacerbate each other, thus triggering a vicious cycle that worsens the prognosis and increases the thromboembolic risk. The optimal management of AF in the context of AHF in the emergency department remains a challenge depending on the time onset, as well as the nature and the severity of the associated symptoms. Acute rate control, along with early rhythm control, when indicated, and anticoagulation represent the main pillars of the therapeutic intervention. The purpose of this review is to elucidate the pathophysiological link between AF and AHF and accordingly present a stepwise algorithmic approach for the management of AF in AHF patients in the emergency setting.

Pulmonary Embolism Prophylaxis in Patients With COVID-19: An Emerging Issue.

Severe acute respiratory syndrome (SARS)-CoV-2 virus disease (coronavirus disease 2019; COVID-19) is associated with increased coagulation activity, resulting in an excessive risk of venous thromboembolism (VTE) and poor prognosis. The most common manifestation of VTE is pulmonary embolism (PE), with approximately one in five hospitalised patients being at risk. These reports led to the empirical use of prophylactic anticoagulation, even in the absence of established or clinically suspected disease. This review summarises current aspects and recommendations regarding the use of thromboprophylaxis for PE in patients with COVID-19.

BRCA1 and BRCA2 germline testing in Cretan isolates reveals novel and strong founder effects.

Germline BRCA1 and BRCA2 loss-of-function variants have been linked to increased breast and ovarian cancer risk, with more than 5,000 distinct pathogenic variants being reported worldwide. Among individuals of Greek descent, the BRCA1/2 variant spectrum is heterogeneous, but characterized by strong founder effects. As patients from certain geographical regions of Greece (like Crete) were underrepresented in previous studies, we hypothesized that isolated Cretans, a southern Greece islanders' population with distinct demographic, cultural and genetic features, could harbor founder BRCA1/2 mutations. A total of 304 breast or/and ovarian cancer patients of Cretan descent, fulfilling NCCN criteria for genetic testing, were tested by NGS or Sanger sequencing, followed by MLPA. Haplotype analysis was subsequently performed to investigate potential founder effects of recurrent alleles. Overall, 16.5% (50/304) of the tested patients carried 22 different pathogenic variants; 48% in BRCA1, 52% in BRCA2. Three variants, namely two in BRCA2 (Δexons 12 and 13 and c.7806-2A>T) and one in BRCA1 (c.5492del), constituting approximately half (48%) of all detected pathogenic variants, were shown to have a founder effect, with all carriers sharing common haplotypes. Remarkably, these variants were confined to Cretans and have not been identified in other regions of Greece. The high prevalence of specific BRCA1/2 pathogenic variants among Cretans, provides the possibility of cost- and time-efficient screening of the Cretan population. Integrating this knowledge in local public health services may have a significant impact on cancer prevention, and may serve as a starting point for the implementation of testing on a population level.

Baseline and 9 months IVUS analysis of the bifurcation-dedicated biolimus A9-eluting Axxess stent system: the DIVERGE IVUS substudy.

BACKGROUND: Percutaneous treatment of complex coronary bifurcation lesions remains challenging, even in the drug-eluting stent era. We sought to evaluate the baseline and 9 months intravascular ultrasound (IVUS) analysis of the Axxess™ stent, a self-expanding, Biolimus A9™-eluting, and dedicated bifurcation stent. METHODS AND RESULTS: We enrolled the first 76 patients from selected sites of the 302 patients large DIVERGE trial (a prospective, single-arm, multicenter trial evaluating the safety and efficacy of the Axxess stent). Both baseline and 9 months IVUS images were collected for serial two-dimensional (2D) and 3D analysis. A minimal amount and a low percentage of neointimal volume index were seen in the Axxess stent at 9 months (0.4 ± 0.6 mm(3) /mm and 4.3 ± 5.2%, respectively). Vessel, lumen, and stent volume indices increased significantly (respectively, 17.0 ± 3.6 to 18.9 ± 3.7 mm(3) /mm, P < 0.0001; 7.3 ± 2.0 to 9.2 ± 2.5 mm(3) /mm, P < 0.0001; and 7.4 ± 2.0 to 9.6 ± 2.6 mm(3) /mm, P < 0.0001). This resulted in minimum lumen area (MLA) enlargement (6.1 ± 1.9 to 7.2 ± 2.3 mm(2) , P < 0.0001), whereas peristent plaque area decreased (8.7 ± 2.5 to 8.5 ± 2.1 mm(3) /mm, P = 0.016). At 9 months, 16 (26%) incomplete stent apposition (ISA) persisted from baseline, while six resolved (9.7%). Only one (2%) ISA was late acquired. In the additional distal sirolimus-eluting stents, MLA decreased from 4.3 ± 1.1 to 4.1 ± 1.2 mm(2) (P = 0.04) at 9 months for the main branch, and from 3.4 ± 1.2 to 3.2 ± 1.2 mm(2) (P = 0.09) for the side branch. CONCLUSIONS: The dedicated bifurcation Axxess stent system demonstrates significant stent volume increase with minimal neointimal formation and a low incidence of late-acquired ISA at 9 months.

Outcomes in diabetic patients undergoing primary percutaneous coronary intervention for acute anterior myocardial infarction: results from the INFUSE-AMI study.

OBJECTIVES: To evaluate the clinical, angiographic, and cardiac magnetic resonance imaging (cMRI) results in patients with and without diabetes mellitus (DM) undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). BACKGROUND: DM has been associated with increased mortality in patients with STEMI, yet the mechanisms underpinning this association have not been completely elucidated. METHODS: Overall, 451 patients (51 diabetics) from the INFUSE-AMI trial were studied. They presented with an anterior STEMI due to an occluded left anterior descending artery (LAD) and underwent bivalirudin-supported primary PCI with or without intralesion abciximab and with or without thrombus aspiration. Angiographic baseline and post-procedure parameters, cMRI at 30 days, and clinical follow-up at 30 days and at 1 year were compared between diabetic and nondiabetic patients. RESULTS: Patients with DM had significantly more comorbidities and more extensive LAD disease than nondiabetics. Primary PCI was equally effective in restoring coronary flow in both groups and the infarct size at 30 days was similar (14.3% [7.1, 24.5] vs. 17.3% [8.1, 23.6], respectively, P = 0.55). Diabetic patients had more major cardiovascular and cerebrovascular events at 1 year (16.5% vs. 8.0%, P = 0.04). Stent thrombosis within 30 days after primary PCI was higher in diabetic than in nondiabetic subjects (4.3% vs. 0.8%, P = 0.03). CONCLUSIONS: Patients with DM presenting with STEMI had a higher baseline risk profile than those without DM. Although reperfusion success and infarct size were similar, diabetic patients experienced more death, reinfarction, stent thrombosis, and revascularization than nondiabetics.

D-dimer levels predict ischemic and hemorrhagic outcomes after acute myocardial infarction: a HORIZONS-AMI biomarker substudy.

D-dimer is a product of cross linked fibrin degradation and is a measure of the amount of fibrin turnover. As such, D-dimer might be of utility in the prediction of both thrombotic and hemorrhagic events. Therefore, the aim of the present study was to evaluate whether elevated D-dimer levels on admission and at discharge could predict subsequent ischemic and hemorrhagic events in patients with acute myocardial infarction (AMI). D-dimer was measured on admission and at discharge in 461 out of a total of 3,602 patients in the HORIZONS-AMI trial, as part of the formal prespecified biomarker substudy. The predictive value for major adverse cardiovascular events (MACE) and non-CABG major bleeding after 3 year follow up was investigated by stratifying patients in groups of D-dimer level and comparing event rates using Kaplan-Meier and calculating hazard ratios using Cox proportional hazards models. D-dimer levels ≥ 0.71 µg/mL on admission were associated with an adjusted hazard ratio of 2.58 for MACE (p = 0.0014) and 4.61 for major bleeding (p = 0.0018). A discharge D-dimer level ≥ 1.26 µg/mL was associated with a higher risk for MACE by univariate analysis (HR 1.88, p = 0.037), but lost its significance after multivariate adjustment (HR 1.77, p = 0.070). High D-dimer levels on admission were associated with a higher risk of MACE and non-CABG major bleeding in STEMI patients undergoing pPCI.

Long-term clinical outcomes after percutaneous coronary intervention for chronic total occlusions.

Optimal treatment of chronic total occlusions (CTOs) remains one of the major challenges in interventional cardiology. A number of factors, including both patient clinical conditions and technical procedural considerations, have been identified to affect percutaneous coronary intervention (PCI) success and long-term outcomes, in large multicenter cohorts as well as smaller patient groups. As opposed to patient-centered factors, technical factors can be managed and as a result, a lot of research aims at improving stent technology and imaging guidance, toward enhancing PCI efficiency, in regards to patient safety.

Exercise and cardiac rehabilitation in hypertensive patients with heart failure with preserved ejection fraction: A position statement on behalf of the Working Group of Arterial Hypertension of the Hellenic Society of Cardiology.

Arterial hypertension is a major cause of cardiovascular morbidity and mortality and the most common cause of comorbidity in heart failure (HF) with preserved ejection fraction (HFpEF). As an adjunct to medication, healthy lifestyle modifications with emphasis on regular exercise are strongly recommended by both the hypertension and the HF guidelines of the European Society of Cardiology. Several long-term studies have shown that exercise is associated with a reduction in all-cause mortality, a favorable cardiac and metabolic risk profile, mental health, and other non-cardiovascular benefits, as well as an improvement in overall quality of life. However, the instructions for the prescriptive or recommended exercise in hypertensive patients and, more specifically, in those with HFpEF are not well defined. Moreover, the evidence is based on observational or small randomized studies, while well-designed clinical trials are lacking. Despite the proven benefit and the guidelines' recommendations, exercise programs and cardiac rehabilitation in patients with hypertensive heart disease and HFpEF are grossly underutilized. This position statement provides a general framework for exercise and exercise-based rehabilitation in patients with hypertension and HFpEF, guides clinicians' rehabilitation strategies, and facilitates clinical practice. It has been endorsed by the Working Group of Arterial Hypertension of the Hellenic Society of Cardiology and is focused on the Health Care System in Greece.

Evolution of intravascular assessment of coronary anatomy and physiology: from ultrasound imaging to optical and flow assessment.

The fact that coronary angiography has limitations in terms of precise estimation and progression of atherosclerosis has been partially overcome during the last years by the use of new techniques. Catheter-based invasive modalities are of a profound clinical importance in regard to accurate assessment of coronary anatomy and physiology and the choice of the appropriate treatment strategy for each patient. Also their potential in clinical investigation projects is of great interest. This current review summarizes the basic principles of these methodologies and evidently highlights not only their use in clinical practice but also their contribution in clinical outcomes.

Enhanced stent imaging improves the diagnosis of stent underexpansion and optimizes stent deployment.

OBJECTIVES: To investigate the clinical value and diagnostic accuracy of enhanced stent imaging (ESI) as compared with quantitative coronary angiography (QCA) and intravascular ultrasound (IVUS). BACKGROUND: ESI is an image acquisition and processing angiography-based software that improves visualization and provides measurements of deployed stents. METHODS: A total of 40 consecutive patients (42 stents) were studied. Stent deployment was evaluated sequentially and independently by angiography, ESI, and IVUS. Following each imaging modality, the operator determined the necessity of postdilation unrelated to the other modalities. Stent diameters were measured off-line by QCA, ESI, and IVUS at several sites along the deployed stent and compared. RESULTS: Following stent deployment and based solely on angiography, the operator decided to postdilate seven of the 42 stents (16.7%). This decision was not changed after reviewing the ESI images of these seven stents. Of the 35 stents not requiring postdilation based on angiography alone, ESI influenced the operator to change the decision and postdilate 10 of 35 stents (28.6%). The ESI-based measurements had better correlation with IVUS (r = 0.721, P < 0.0001) than did QCA with IVUS (r = 0.563, P < 0.0001). Bland-Altman analysis showed a trend towards better agreement between ESI and IVUS than between QCA and IVUS (mean differences = 0.038 vs. 0.121; P = 0.19, respectively). CONCLUSIONS: ESI is an easy to use modality that enhances stent visualization, helps in the decision making process whether to postdilate the stent, and provides estimation of stent expansion with better correlations than QCA when compared to IVUS. © 2012 Wiley Periodicals, Inc.

Volumetric intravascular ultrasound assessment of mechanisms and results of stent expansion in heart transplant patients.

BACKGROUND: Percutaneous coronary intervention with stent placement for the treatment of patients with cardiac allograft vasculopathy is common, but data regarding stent behavior in this setting is lacking. OBJECTIVES: We investigated mechanisms and potential differences in stent expansion among transplant patients vs. patients with native coronary artery atherosclerotic disease ("controls"). METHODS: We compared pre- and poststent intravascular ultrasound in 12 transplant patients (17 lesions) and 33 control patients (34 lesions) matched according to age (60.1 ± 9.2 years), diabetes mellitus, and lesion location. Planar and volumetric analysis was conducted for every 1 mm at the lesion site as well as the first 5 mm proximal and distal to the stent edge. Focal stent expansion was defined as minimum stent area (MSA) divided by mean reference lumen area. Diffuse stent expansion was defined as mean stent area divided by mean reference lumen area. RESULTS: Transplant patients had more plaque than "controls" prestenting, but similar MSA and focal and diffuse stent expansion afterwards. The increase in mean lumen area correlated with the increase in mean vessel area in both groups, transplant (R = 0.64, P = 0.008) and controls (R = 0.70, P < 0.0001), but correlated inversely with changes in mean plaque area only in the transplant group (R = 0.55, P = 0.027). There were no differences in calcification between the two groups and no axial plaque distribution from the lesion into the reference segments in either group. CONCLUSIONS: The mechanism of stent expansion in transplant vasculopathy appears to be similar to de novo atherosclerosis-i.e., mainly vessel expansion to achieve similar acute results.

Relationship between biomarkers and subsequent bleeding risk in ST-segment elevation myocardial infarction patients treated with paclitaxel-eluting stents: a HORIZONS-AMI substudy.

Major bleeding complications in STEMI patients result in significant mortality, morbidity and healthcare cost. Identification of patients at increased risk of bleeding is therefore essential. New biomarkers might be of incremental value to identify patients at risk for bleeding after primary PCI. A total of 26 biomarkers were measured at enrolment and analyzed at a central core laboratory in 464 STEMI patients in the HORIZONS-AMI trial. We investigated the relationship between tertiles of biomarker and in hospital non-CABG major bleeding. In hospital non-CABG major bleeding occurred in 3.7% of patients (n = 17). Increasing levels of cystatin C and D-dimer at admission were associated with higher rates of in hospital major bleeding. After adjustment for a risk score for bleeding, the odds ratio for in hospital major bleeding was 3.13 for cystatin C > 2.04 mg/L (p = 0.046) and 3.28 for ESAM > 34 ng/mL (p = 0.037). In this exploratory analysis of the HORIZONS-AMI biomarker substudy, high cystatin C and ESAM levels were associated with a higher risk of major bleeding. Larger studies are warranted to confirm the prognostic value of cystatin C and ESAM for major bleeding in STEMI patients.

Relationship between biomarkers and subsequent clinical and angiographic restenosis after paclitaxel-eluting stents for treatment of STEMI: a HORIZONS-AMI substudy.

Drug-eluting stents (DES) reduce the incidence of in-stent restenosis (ISR) after primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI). Whether the use of biomarkers might be of utility to identify patients who remain at risk for DES ISR after primary PCI has never been examined. A total of 26 biomarkers were measured at enrollment and 30 days and analyzed at a central core laboratory in 501 STEMI patients from the HORIZONS-AMI trial. All patients underwent primary PCI with the TAXUS paclitaxel-eluting stent (PES), were scheduled for routine angiographic follow-up at 13 months, and were followed for 3 years. Mean in-stent late-loss was 0.28 ± 0.57 mm, and target lesion revascularization (TLR) at 3 years occurred in 9.1 % of patients. Low levels of interleukin-6 (IL-6) and placental growth factor (PLGF) at admission were associated with both higher in-stent late loss and ischemia-driven TLR. Additionally, low admission levels of cardiotrophin-1 (CT-1) were associated with higher rates of ischemia-driven TLR. At 30-day follow-up lower values of IL-1ra (IL-1ra), matrix metalloproteinase 9 (MMP9), and myeloperoxidase (MPO), and a decline relative to admission in IL-1ra, monocyte chemotactic protein-1 (MCP-1), and MMP9 were associated with higher in-stent late loss. Low values of IL-6 at 30 days were also associated with ischemia-driven TLR. After multivariate adjustment, only MPO at 30 days and a decline of MCP-1 between admission and 30 days were associated with in-stent late loss, and only CT-1 was associated with TLR. MPO at 30 days and a decline of MCP-1 between admission and 30 days were independently associated with in-stent late loss, and CT-1 was associated with TLR. Additional studies to confirm and validate the utility of these biomarkers are warranted.

Hemostasis parameters disturbances in healthy individuals with prehypertension.

Prehypertension (PH) seems to be related to increased cardiovascular risk in healthy normotensive subjects, while essential hypertension is associated with hemostasis balance disturbances. The aim of our study was to examine the impact of PH on hemostasis parameters in healthy individuals with PH and to compare the findings with those of healthy normotensives with normal blood pressure (NBP) levels. This study was performed in 204 (96 M, 108 F) subjects who attended our hypertension clinic. Seventy-eight (36 M, 42 F) subjects with PH, mean age 52 ± 5 years, and body mass index (BMI) 23 ± 1.5 kg/m2 made up group A, and 126 (60 M, 66 F) subjects with NBP, mean age 53 ± 6 years, and BMI 23.2 ± 1.4 kg/m2 without any history of cardiovascular disease or diabetes mellitus made up group B. Systolic blood pressure and diastolic blood pressure were measured in three sequential visits, which were performed by the same trained nurse. Serum lipid levels, fibrinogen (F), thrombomodulin (TM), and plasminogen activator inhibitor-1 antigen, and tissue plasminogen activator antigen were determined in the whole population. Plasminogen activator inhibitor-1 antigen and tissue plasminogen activator antigen levels were significantly higher in the PH group as compared with normotensives, while in PH subjects, significantly higher plasma levels of F and TM were found compared with normotensive group. The two groups were matched for age, sex, BMI, and serum lipid levels. Our findings indicate that PH is associated with hemostasis disturbances predisposing to hypercoagulability and impaired fibrinolysis. This observation may be of prognostic value for future cardiovascular events in this group and needs further investigation.

Antihypertensive Drugs and Risk of Bone Fractures.

Antihypertensive drugs are among the most documented regimens worldwide with an overall survival and cardioprotective benefit. However, there is evidence that they cause symptoms of orthostatic hypotension (i.e., dizziness and syncope) placing patients at risk for falls and fall-related injuries such as bone fractures. Moreover, it seems that they might impact bone metabolism and architecture impairing bone health. The aim of this review was to summarize the accumulative literature exploring any potential association between several antihypertensive medications including diuretics, renin-angiotensin-aldosterone system inhibitors, beta-blockers and calcium channel blockers and the risk of fractures.

Impact of baseline thrombocytopenia on the early and late outcomes after ST-elevation myocardial infarction treated with primary angioplasty: analysis from the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial.

BACKGROUND: Thrombocytopenia (TP) is a common abnormality in patients presenting with acute coronary syndrome. Whether baseline TP has any influence on the outcome of patients treated with primary angioplasty for acute myocardial infarction is unknown. METHODS: We sought to detect the impact of baseline TP on the early and late outcomes of patients with ST-elevation myocardial infarction in the HORIZONS-AMI trial that included a protocol of immediate angiography and primary percutaneous coronary intervention. RESULTS: Baseline TP was found in 4.2% of patients and was associated with a higher incidence of cardiovascular mortality, major bleeding, and major cardiovascular events at short- and long-term follow-up. The 30-day rates of death, major bleeding, major cardiac events, and major cardiac events plus major bleeding were 6.2%, 11.9%, 9.6%, and 18.5% in the TP group, respectively, compared with 2.1%, 7%, 5.2%, and 10.8% in those without TP (P < .05 for all). Similarly, event rates at 2 years were 11.3%, 12.7%, 24.7%, and 30.8% compared with 5.1%, 7.9%, 18.5%, and 23.3% (P < .05). By multivariate analysis, baseline TP was an independent predictor of 30-day net adverse clinical events but not of any 2-year events. CONCLUSIONS: We found that baseline TP in patients with ST-elevation myocardial infarction undergoing routine angiography and primary percutaneous coronary intervention is strongly associated with early adverse events and is a maker of late events, related to both ischemia and bleeding.

Renin Angiotensin Aldosterone System Inhibitors in Chronic Kidney Disease: A Difficult Equation.

Chronic kidney disease (CKD) is a global health problem and is strongly associated with hypertension (HTN) and impaired quality of life. Managing HTN with agents that block the renin angiotensin aldosterone system (RAAS) remains the gold standard, however there is a misleading impression that patients with impaired renal function or those receiving hemodialysis should not be treated with RAAS inhibitors. To date, only a few data in this field are available, given that this population subset is systematically excluded from many major clinical trials. The purpose of this review was to solve the difficult equation regarding the optimal use of RAAS blockade in patients with CKD.