Caseous calcification of the mitral annulus presenting as recurrent strokes.

Although caseous calcification of the mitral annulus is usually diagnosed incidentally, it can cause embolic complications. The current report describes the case of caseous calcification revealed by recurrent episodes of stroke in a 64-year-old female patient. After her last ischemic episode, cerebral magnetic resonance imaging confirmed the presence of a thrombus in the right middle cerebral artery. Transthoracic echocardiogram revealed calcification of the mitral annulus and an echo-dense mass with mobile borders fixed posteriorly. Transesophageal echocardiogram allowed better evaluation of the lesion. A medical approach was preferred, with no recurrence thereafter. Learning objective: Caseous calcification of the mitral annulus is a rare form of mitral annular calcification which is associated with high risk of strokes.Medical management with optimal anticoagulation can be effective over long-term follow up.

Prospective Phenotyping of Right Ventricle Function Following Intra-Aortic Balloon Pump Counterpulsation in Left Ventricular Assist Device Candidates: Outcomes and Predictors of Response.

Intra-aortic balloon pump (IABP) may be applied to optimize advanced heart failure (AHF) patients and improve right ventricular (RV) function before left ventricular assist device (LVAD) implantation. We aimed to evaluate the outcome of this intervention and define RV response predictors. Decompensated AHF patients, not eligible for LVAD because of poor RV function, who required IABP for stabilization were enrolled. Echocardiography and invasive hemodynamics were serially applied to determine fulfillment of prespecified "LVAD eligibility RV function" criteria (right atrium pressure [RA] <12 mm Hg, pulmonary artery pulsatility index [PAPi] >2.00, RA/pulmonary capillary wedge pressure [PCWP] <0.67, RV strain <-14.0%). Right ventricular-free wall tissue was harvested to assess interstitial fibrosis. Eighteen patients (12 male), aged 38 ± 14 years were supported with IABP for 55 ± 51 (3-180) days. In 11 (61.1%), RV improved and fulfilled the prespecified criteria, while seven (38.9%) showed no substantial improvement. Histopathology revealed an inverse correlation between RV interstitial fibrosis and functional benefit following IABP: interstitial fibrosis correlated with post-IABP RA ( r = 0.63, p = 0.037), RA/PCWP ( r = 0.87, p = 0.001), PAPi ( r = -0.83, p = 0.003). Conclusively, IABP improves RV function in certain AHF patients facilitating successful LVAD implantation. Right ventricular interstitial fibrosis quantification may be applied to predict response and guide preoperative patient selection and optimization. http://links.lww.com/ASAIO/A995.

Human immunodeficiency virus type 1 impairs sumoylation.

During infection, the human immunodeficiency virus type 1 (HIV-1) manipulates host cell mechanisms to its advantage, thereby controlling its replication or latency, and evading immune responses. Sumoylation is an essential post-translational modification that controls vital cellular activities including proliferation, stemness, or anti-viral immunity. SUMO peptides oppose pathogen replication and mediate interferon-dependent anti-viral activities. In turn, several viruses and bacteria attack sumoylation to disarm host immune responses. Here, we show that HIV-1 impairs cellular sumoylation and targets the host SUMO E1-activating enzyme. HIV-1 expression in cultured HEK293 cells or in CD4+ Jurkat T lymphocytes diminishes sumoylation by both SUMO paralogs, SUMO1 and SUMO2/3. HIV-1 causes a sharp and specific decline in UBA2 protein levels, a subunit of the heterodimeric SUMO E1 enzyme, which likely serves to reduce the efficiency of global protein sumoylation. Furthermore, HIV-1-infected individuals display a significant reduction in total leukocyte sumoylation that is uncoupled from HIV-induced cytopenia. Because sumoylation is vital for immune function, T-cell expansion and activity, loss of sumoylation during HIV disease may contribute to immune system deterioration in patients.

Sumoylation of Cas9 at lysine 848 regulates protein stability and DNA binding.

CRISPR/Cas9 is a popular genome editing technology. Although widely used, little is known about how this prokaryotic system behaves in humans. An unwanted consequence of eukaryotic Cas9 expression is off-target DNA binding leading to mutagenesis. Safer clinical implementation of CRISPR/Cas9 necessitates a finer understanding of the regulatory mechanisms governing Cas9 behavior in humans. Here, we report our discovery of Cas9 sumoylation and ubiquitylation, the first post-translational modifications to be described on this enzyme. We found that the major SUMO2/3 conjugation site on Cas9 is K848, a key positively charged residue in the HNH nuclease domain that is known to interact with target DNA and contribute to off-target DNA binding. Our results suggest that Cas9 ubiquitylation leads to decreased stability via proteasomal degradation. Preventing Cas9 sumoylation through conversion of K848 into arginine or pharmacologic inhibition of cellular sumoylation enhances the enzyme's turnover and diminishes guide RNA-directed DNA binding efficacy, suggesting that sumoylation at this site regulates Cas9 stability and DNA binding. More research is needed to fully understand the implications of these modifications for Cas9 specificity.

Missed Heparin-Induced Thrombocytopenia (HIT) Diagnosis in a Patient with Acute Stent Thrombosis.

BACKGROUND Heparin-induced thrombocytopenia (HIT) is a serious complication of heparin therapy, characterized by thrombocytopenia and high risk for venous and arterial thrombosis. CASE REPORT We report an unusual case of acute stent thrombosis secondary to delayed HIT. A 74-year-old man with non-ST-segment elevation myocardial infarction had a coronary angiography which revealed 2-vessel disease. A bolus of unfractionated heparin (UFH) was administered at admission and he received fondaparinux during his hospitalization. We performed elective percutaneous coronary intervention (PCI) with stents to LAD and LCx. Two hours after PCI, the patient developed acute pulmonary edema, and repeat angiography revealed an occlusive thrombus in the ostial LAD and the LCx. A turbidimetric assay for the rapid detection of plasma anti-PF4/heparin antibodies was negative. After repeated unsuccessful attempts of balloon angioplasty and continuous thrombosis, the patient was transferred for emergency surgical revascularisation and was treated with additional UFH followed by enoxaparin. Platelets decreased gradually to 38 k/µl 7 days after surgery, at which time enoxaparin was replaced with fondaparinux. The subsequent HIT test results were positive. CONCLUSIONS HIT should be considered in patients with multiple recent exposures to anticoagulants, independent of the platelet count, if there are signs and symptoms of thrombosis.

Platelet to lymphocyte ratio in acute aortic dissection.

BACKGROUND: Inflammation plays an important role in the initiation and progression of acute aortic dissection (AAD). New inflammatory indices derived from full cell blood count and its differential may be associated with increased risk. We evaluated platelet-lymphocyte (PLR), red cell distribution width (RDW) and RDW/PLT's (platelets) (RPR) in AAD. METHODS: We studied 120 consecutive patients with AAD type I admitted for emergency surgery (group I), 121 consecutive patients with aortic aneurysms of the ascending aorta prior to elective repair (group II) and 121 controls (group III), age and sex matched. RESULTS: PLR was significantly higher in group I vs both groups II and III (P < .001). There was an excellent correlation of PLR with neutrophil/lymphocyte ratio (NLR) in all three groups (P < .001 for all). After adjustment for hemoglobin, RDW did not differ but RPR remained significantly higher in group I compared to groups II and III (P < .001). The best cutoff value of PLR to predict dissection was 159 with 53% sensitivity and 86% specificity. No association between PLR, RDW, and RPR and mortality in group I was found. CONCLUSIONS: Indices derived from full cell blood count may provide diagnostic information in patients with AAD; whether these indices may contribute to prognosis assessment should be further investigated.

Dyspnoea on exertion in a 53-year-old woman.

CLINICAL INTRODUCTION: A 53-year-old woman with no previous medical history complained of easy fatigue over the last 6 months. She had a positive family history for coronary artery disease but no other risk factors. On physical examination, a 3/6 pansystolic murmur was heard over the apex, and the lung auscultation was unremarkable. Her ECG showed a left anterior fascicular block, with poor R wave progression in the anterior leads (see online supplementary image A). A subsequent echocardiogram revealed a slightly dilated for the patient's body surface area (BSA) (1.73 m2) left ventricle (55/35 mm), with preserved systolic function and a moderate functional mitral regurgitation. The estimated pulmonary artery pressure was 45 mm Hg. During treadmill radionuclide scintigraphy, her exercise tolerance was normal, with good inotropic response, and 96% oxygen saturation at rest and at peak exercise. A 2 mm ST segment depression was noted at peak effort, which persisted well into recovery (see online supplementary image B). The scintigraphy scan showed extensive reversible anteroapical wall ischaemia (see online supplementary image C). At this point she was referred to us for right and left heart catheterisation. Intracardiac pressures and saturations were: right atrium (RA)RA=3 mm Hg, right ventricle (RV)=26/3 mm Hg, Pulmonary artery (PA)=26/10/mean 16 mm Hg, pulmonary capillary wedge pressure (PCWP)=11 mm Hg, left ventricle (LV)=110/10 mm Hg, Aorta (Ao)=110/60/mean 80 mm Hg, Superior vena cava saturation (SVCsat)=62%, RAsat=62%, PAsat=78%, Aosat=96% and estimated pulmonary to systematic flow ratio (Qp/Qs)=1.8. Her coronary angiography and CT angiography are shown in figure 1A,B.DC1SP110.1136/heartjnl-2017-311256.supp1Supplementary material 1 DC2SP210.1136/heartjnl-2017-311256.supp2Supplementary material 2 DC3SP310.1136/heartjnl-2017-311256.supp3Supplementary material 3 heartjnl;103/17/1390/F1F1F1Figure 1Coronary and CT angiograms. QUESTION: What is the most likely diagnosis?Right coronary fistula to right ventricleKawasaki disease with fistulaAnomalous origin of the left coronary artery from the pulmonary arteryPersistent truncus arteriosus.

Osteopontin in relation to Prognosis following Coronary Artery Bypass Graft Surgery.

Cardiovascular events may occur even after complete revascularization in patients with coronary artery disease. We measured preoperative osteopontin (OPN) levels in 131 consecutive patients (66.5 ± 10 years old, 117 men and 14 women) with left ventricular ejection fraction of 50.7 ± 9.2% and low logistic EuroScore (3.5 ± 3.2%) undergoing elective Coronary Artery Bypass Grafting (CABG) surgery. Patients were prospectively followed up for a median of 12 months (range 11-24). The primary study endpoint was the composite of cardiovascular death, nonfatal myocardial infarction, need for repeat revascularization, and hospitalization for cardiovascular events. Pre-op OPN plasma levels were 77.9 (49.5, 150.9). Patients with prior acute myocardial infarction (AMI) had significantly higher OPN levels compared to those without [131.5 (52.2, 219) versus 73.3 (45.1, 125), p = 0.007]. OPN levels were positively related to EuroScore (r = 0.2, p = 0.031). Pre-op OPN levels did not differ between patients who had a major adverse event during follow-up compared to those with no event (p = 0.209) and had no effect on the hazard of future adverse cardiac events [HR (95% CI): 1.48 (0.43-4.99), p = 0.527]. The history of AMI was associated with increased risk of subsequent cardiovascular events at follow-up (p = 0.02). OPN is associated with preoperative risk assessment prior to low-risk CABG but did not independently predict outcome.

Radial Interventions: Present and Future Indications.

OPINION STATEMENT: Since its first introduction, radial access for diagnostic and interventional cardiovascular procedures has progressively evolved with advances in understanding, capabilities, and ease of operation. Numerous studies have demonstrated its safety, efficacy, and cost-effectiveness. Overall, radial catheterization is a valid alternative to the femoral approach with additional benefits of shorter length of hospital stay and reduced patient costs when performed by experienced interventionists. Moreover, with reduced rates of access site complications and enhanced patient satisfaction, the transradial approach has emerged as the preferred vascular access route for most coronary interventions, even in cases of acute myocardial infarction.

Prognostic performance of critical care scores in patients undergoing transcatheter aortic valve implantation.

BACKGROUND: Critical care management of patients undergoing transcatheter aortic valve implantation (TAVI) is a major determinant of their outcome. AIMS: The aim of this study was to compare the prognostic performance of four general scoring systems [Acute Physiology and Chronic Health Evaluation (APACHE), Simplified Acute Physiology Score (SAPS), Sequential Organ Failure Assessment (SOFA), and MultiOrgan Dysfunction (MOD) scores] in TAVI patients. METHODS: Between 1 June 2008 and 30 June 2014, 75 patients (81.2 ± 6.4 years old, 36 men and 39 women) who underwent TAVI were scored during the first 24 h of their stay at the intensive care unit (ICU). The outcome measures were in-hospital and 30-day mortality and in-hospital and 30-day morbidity defined as myocardial infarction, implantation of permanent pacemaker, stroke, tamponade, major bleeding, vascular access site complications and prolonged ventilation. RESULTS: Four patients (5.3%) died in ICU and one more during follow-up, indicating a 30-day mortality rate of 6.6%. Regarding in-hospital mortality, the area under the ROC curve (AUC) was 0.92 for SAPS II, 0.88 for APACHE II, 0.73 for MODS and 0.74 for SOFA. Regarding 30 day-mortality, SAPS II and APACHE II performed equally higher (AUC = 0.88) than the other two scores (0.79 for MODS and 0.80 for SOFA). SAPS II had the best calibration among all four scores for in-hospital and 30-day mortality (χ2 = 3.06 and χ2 = 3.29, respectively). AUCs for in-hospital and 30-day morbidity were above 0.7 for SAPS II and APACHE II. CONCLUSIONS: SAPS II and APACHE II are reliable mortality and morbidity risk stratification models for TAVI patients with high calibration and discrimination.

High neutrophil to lymphocyte ratio in type A acute aortic dissection facilitates diagnosis and predicts worse outcome.

OBJECTIVE: The authors investigated whether neutrophil to lymphocyte ratio (N/L) can contribute to the diagnosis and risk assessment in patients with type A acute aortic dissection (AAD). METHODS: The authors studied 120 consecutive patients with type A AAD (group I) and compared them with 121 consecutive patients with chronic aneurysms (group II) and 121 age- and sex-matched healthy subjects (group III). RESULT: It was found that white blood cell count, N/L, D-dimer and C-reactive protein were significantly higher in group I versus both groups II and III (p < 0.001 for all comparisons). White blood cell count and D-dimer were much higher in patients who died compared to survivors in group I (p = 0.023 and p = 0.033, respectively). A cutoff value of N/L >4.6 was associated with 0.89 sensitivity and 0.91 specificity for AAD. CONCLUSION: High N/L may contribute to the diagnostic evaluation and prompt immediate therapy in patients with type A AAD.

Heart rate and B-blockade in stable coronary artery disease in Greece.

INTRODUCTION: Heart rate (HR) is a strong prognostic indicator in patients with coronary artery disease (CAD). However, there is only limited evidence on HR and the use of b-blockers in patients with CAD in contemporary clinical practice. METHODS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis >50%, or chest pain associated with proven myocardial ischemia. A total of 33,283 patients from 45 countries were enrolled between November 2009 and July 2010; of these, 559 patients were enrolled in Greece (age 62.3 ± 10.6 years, 84.44% men). RESULTS: HR measured by pulse was 68.3 ± 10.2 bpm and by electrocardiogram 67.6 ± 10.9, with an excellent correlation (r=0.91, p<0.001). Overall, 42.8% had HR70 bpm. B-blockers were prescribed in 74.2% of patients. Resting HR by pulse on b-blocker was 67.8 bpm and without b-blocker 69.6 bpm (p=0.069). HR70 bpm was independently associated with a lack of physical activity, higher systolic blood pressure, and a higher prevalence of asthma or chronic obstructive pulmonary disease and carotid artery disease. CONCLUSION: Despite the use of HR lowering agents, the percentage of patients with HR70 bpm was high. It is likely that we can further improve HR control in Greek patients with stable CAD by both increasing the prescription of b-blockers and up-titrating their dose, as well as by using and up-titrating other available HR lowering agents.

Clinical presentation and management of stable coronary artery disease: insights from the international prospective CLARIFY registry - results from the Greek national cohort.

INTRODUCTION: Coronary artery disease (CAD) is highly prevalent worldwide, yet there is a paucity of data regarding the clinical characteristics and management of outpatients with stable CAD. In this paper, we report the baseline data of the Greek cohort and we compare our national data with the global results of the entire registry, as well as the results from the western European countries. METHODS: CLARIFY is an international, prospective, observational, longitudinal registry of outpatients with stable CAD, defined as prior myocardial infarction or revascularization procedure, evidence of coronary stenosis >50%, or chest pain associated with proven myocardial ischemia. A total of 33,283 patients from 45 countries in 4 continents were enrolled between November 2009 and July 2010; of these, 14,726 were from western European countries (Austria, Belgium, Denmark, France, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the United Kingdom) and 559 patients were enrolled in Greece. RESULTS: Compared to their counterparts in western Europe and the entire cohort, Greeks were younger (p<0.0001, p<0.0001, respectively), more predominantly male (p<0.0039, p<0.0001), with a higher body mass index (p<0.0002, p<0.0001) and a larger waist circumference (p<0.0001, p<0.0001), as well as a higher prevalence of family history of CAD (p<0.0008, 0.0005), hyperlipidemia (p<0.0001, p<0.0001) and smoking (p<0.0001, p<0.0001). Noninvasive testing (p<0.0001, p<0.0001, respectively) and coronary angiography (p<0.0001, 0.0013) along with surgical revascularization (CABG) (p<0.0001, 0.0088) were performed more often in Greece. Antiplatelets, b-blockers and lipid lowering medications were used to an equal extent in Greece as in the other two cohorts. CONCLUSION: There are substantial differences in demographics, clinical profiles and treatment in patients with stable CAD within the data set, which are also observed for Greek data. Interestingly, these differences are consistent in relation to the global as well as the western European data.

Left ventricular pseudoaneurysm formation: Two cases and review of the literature.

Left ventricular wall rupture (LVWR) comprises a complication of acute myocardial infarction (AMI). Acute LVWR is a fatal condition, unless the formation of a pseudoaneurysm occurs. Several risk factors have been described, predisposing to LVWR. High index of suspicion and imaging techniques, namely echocardiography and computed tomography, are the cornerstones of timely diagnosis of the condition. As LVWR usually leads to death, emergency surgery is the treatment of choice, resulting in significant reduction in mortality and providing favorable short-term outcomes and adequate prognosis during late follow-up. Herein, we present two patients who were diagnosed with LVWR following AMI, and subsequent pseudoaneurysm formation. In parallel, we review the aforementioned condition.

Transcatheter aortic valve implantation: restoring the qualities of life in old age.

Transcatheter aortic valve implantation (TAVI) is a tremendous therapeutic advance for patients with severe aortic stenosis and high-surgical risk. Since TAVI-treated patients are elderly with multiple co-existing conditions, limited life expectancy and disproportionate health-care expenditures, the aspect of the health-related quality of life (HRQoL) benefits becomes of fundamental importance. Based on recent evidence, TAVI appears to improve significantly HRQoL measures compared with optimal standard care, which are restored to age-adjusted population norms over time.