Prevalence of diabetic cardiomyopathy in patients with type 2 diabetes in a large academic medical center.

BACKGROUND: Diabetic cardiomyopathy (DbCM) is characterized by asymptomatic stage B heart failure (SBHF) caused by diabetes-related metabolic alterations. DbCM is associated with an increased risk of progression to overt heart failure (HF). The prevalence of DbCM in patients with type 2 diabetes (T2D) is not well established. This study aims to determine prevalence of DbCM in adult T2D patients in real-world clinical practice. METHODS: Retrospective multi-step review of electronic medical records of patients with the diagnosis of T2D who had echocardiogram at UC San Diego Medical Center (UCSD) within 2010-2019 was conducted to identify T2D patients with SBHF. We defined "pure" DbCM when SBHF is associated solely with T2D and "mixed" SBHF when other medical conditions can contribute to SBHF. "Pure" DbCM was diagnosed in T2D patients with echocardiographic demonstration of SBHF defined as left atrial (LA) enlargement (LAE), as evidenced by LA volume index ≥ 34 mL/m2, in the presence of left ventricular ejection fraction (LVEF) ≥ 45%, while excluding overt HF and comorbidities that can contribute to SBHF. RESULTS: Of 778,314 UCSD patients in 2010-2019, 45,600 (5.9%) had T2D diagnosis. In this group, 15,182 T2D patients (33.3%) had echocardiogram and, among them, 13,680 (90.1%) had LVEF ≥ 45%. Out of 13,680 patients, 4,790 patients had LAE. Of them, 1,070 patients were excluded due to incomplete data and/or a lack of confirmed T2D according to the American Diabetes Association recommendations. Thus, 3,720 T2D patients with LVEF ≥ 45% and LAE were identified, regardless of HF symptoms. In this group, 1,604 patients (43.1%) had overt HF and were excluded. Thus, 2,116 T2D patients (56.9% of T2D patients with LVEF ≥ 45% and LAE) with asymptomatic SBHF were identified. Out of them, 1,773 patients (83.8%) were diagnosed with "mixed" SBHF due to comorbidities such as hypertension (58%), coronary artery disease (36%), and valvular heart disease (17%). Finally, 343 patients met the diagnostic criteria of "pure" DbCM, which represents 16.2% of T2D patients with SBHF, i.e., at least 2.9% of the entire T2D population in this study. CONCLUSIONS: Our findings provide insights into prevalence of DbCM in real-world clinical practice and indicate that DbCM affects a significant portion of T2D patients.

Postural Orthostatic Tachycardia Syndrome: Prevalence, Pathophysiology, and Management.

Postural orthostatic tachycardia syndrome (POTS) is a debilitating disease that predominantly affects young women. It is a multifactorial disorder that is characterized by severe tachycardia and orthostatic intolerance. Patients with POTS experience a variety of cardiac, neurological, and immunological symptoms that significantly reduce quality of life. In this review, a comprehensive framework is provided to aid in helping identify and treat patients with POTS. Given its heterogenous nature, it is crucial to understand each component of POTS in relation to one another instead of distinct parts. The framework highlights the overlap among the five main subtypes of POTS based on its pathophysiology (neuropathic, hypovolemic, primary hyperadrenergic, joint-hypermobility-related, and immune-related). Emphasis is placed on incorporating a multidisciplinary approach when treating patients with POTS, especially with a new focus towards immunotherapy. Although research has advanced our knowledge of POTS, there is still a critically unmet need to further our understanding and provide patients with the relief they need.

Prediction of high risk of non-adherence to antiplatelet treatment.

BACKGROUND: Dual antiplatelet therapy with acetylsalicylic acid (ASA) and clopidogrel is the standard of care for secondary prevention. Premature discontinuation of clopidogrel is associated with an increased risk of myocardial infarction (MI) or death, and greater health care expenditure. AIM: To develop an objective method for identification of patients with high risk of non-adherence to clopidogrel after MI. METHODS: A total of 189 patients were enrolled into a prospective, observational, single-centre study with a nine-month follow-up. Patients received a 600-mg loading dose and 75-mg maintenance dose of clopidogrel in combination with ASA doses of 300 mg and 75 mg, respectively. Adenosine diposphate-induced platelet aggregation (ADP-PA) was assessed during baseline hospitalisation and at three, six, and nine months after discharge. Adherence to medication with clopidogrel was defined as the proportion of drug availability based on data from the National Health Fund regarding prescribed drug purchases. Adherence was arbitrarily judged adequate when the proportion exceeded 80%. RESULTS: According to our hypothesis, ADP-PA in non-adherent patients should be higher at follow-up visits (at least once) as compared with measurement at hospitalisation. Based on the ROC curve analysis, the optimal cut-off point equal to 4 U was defined (p < 0.0001, 95% CI 0.562-0.654; sensitivity: 60.6%, specificity: 57.1%, positive predictive value: 63.3%, negative predictive value: 54.2%). The prevalence of true adherence to medication in groups of high and low probability of adherence defined according to developed criteria amounted 60 (50.8%) and 23 (32.4%) cases, respectively (p = 0.01). CONCLUSIONS: The newly developed method of objective identification of patients with high risk of non-adherence to clopidogrel after MI is easily applicable and cheap, and, despite relatively low sensitivity and specificity, it efficiently differentiates patients with regard to clinical end-points during follow-up.

Associations between selected angiographic parameters and the number of CD34⁺ cells and plasma levels of vascular endothelial growth factor and angiogenin in patients with ST-segment elevation myocardial infarction.

INTRODUCTION: Left ventricular (LV) function and prognosis in patients after myocardial infarction are associated with some angiographic parameters. OBJECTIVES: The aim of the study was to assess the associations between the TIMI score in the infarct-related artery (IRA) before percutaneous coronary intervention (PCI), myocardial blush grade (MBG) following effective PCI, and the extent of collaterals measured using the Rentrop scale and plasma levels of vascular endothelial growth factor (VEGF) and angiogenin, number of CD34⁺ cells, as well as LV ejection fraction (LVEF) and wall motion score index (WMSI). PATIENTS AND METHODS: In 62 patients with the first ST-segment elevation myocardial infarction (STEMI) treated with PCI and bare metal stent implantation, plasma VEGF and angiogenin levels as well as the number of CD34⁺ cells were assessed before PCI, 24 hours after PCI, at discharge, and at 30 days following STEMI. LVEF and WMSI were evaluated by echocardiography at discharge and at 1 and 6 months after STEMI. RESULTS: Patients with TIMI 0-1 flow in the IRA before PCI (64.6% of the patients) had significantly higher troponin I and VEGF levels as well as a higher number of CD34⁺ cells than patients with TIMI 3 flow. Patients with TIMI 0-1 flow also had worse LV systolic function at 1 and 6 months following STEMI. Neither the MBG grade nor the Rentrop score showed associations with the mobilization of CD34⁺ cells, VEGF and angiogenin levels, and parameters of L V systolic function. CONCLUSIONS: Early patency of the IRA and lower myocardial necrosis seem to be more important for LV function assessed in patients 6 months after STEMI than mobilization of CD34⁺ cells and levels of angiogenic factors.

Discrepancies in assessment of adherence to antiplatelet treatment after myocardial infarction.

The poor response to clopidogrel is multifactorial and includes, amongst others, low patient adherence to medication. The aim of this study was to assess the reported patient adherence to treatment with clopidogrel and confront it with adherence assessed by drug availability. We evaluated determinants of adherence and its impact on platelet aggregation and clinical outcome. The study population comprised 184 patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. Patient adherence to clopidogrel was defined according to self-reported drug intake and verified based on data from the National Health Fund regarding the purchase of prescribed drugs. The patients were judged as adherent when the proportion of drug availability exceeded 80%. According to drug availability, 100 (54.3%) patients were adherent and 84 (45.7%) were nonadherent. The analysis identified the following factors as predictors of low adherence (<80%): adenosine diphosphate-induced platelet aggregation (ADP-PA) during hospitalization ≤45 U, male gender and occurrence of ST-elevation myocardial infarction [(STEMI) vs. non-STEMI (NSTEMI)], while three-vessel disease was predictive of high adherence to medication. Compared with drug availability-based assessment, self-reported drug intake was significantly different: 172 (94.5%) patients reported regular and 10 (5.5%) patients reported irregular intake of clopidogrel. Clinical follow-up suggested that the self-reported nonregular clopidogrel intake may discriminate patients with a high risk of cardiovascular events. We demonstrated a huge discrepancy between the two most widely used methods for the evaluation of adherence to clopidogrel in secondary prevention treatment in patients after STEMI and NSTEMI. ADP-PA during hospitalization ≤45 U, male gender and STEMI (vs. NSTEMI) were independent predictors of nonadherence while three-vessel disease was independently predictive of adherence to treatment with clopidogrel in the investigated population.

Time-related changes in determinants of antiplatelet effect of clopidogrel in patients after myocardial infarction.

Substantial variability of antiplatelet action is an important limitation of clopidogrel. The aim of this study was to evaluate time-related changes in determinants of clopidogrel responsiveness in patients after myocardial infarction. The study population comprised 191 consecutive patients treated with primary percutaneous coronary intervention for acute myocardial infarction. Follow-up visits were scheduled at 3, 6 and 9 months after discharge. ADP-induced platelet aggregation was tested with Multiplate Analyzer. Patients with ADP-PA>46.8U were defined as clopidogrel non-responders. The prevalence of clopidogrel non-responsiveness was highest during hospitalization and at 9 month follow-up visit, while it was lowest at 3 and 6 months after myocardial infarction (P=0.004). According to multivariate analysis, platelet count, mean platelet volume, concentration of hsCRP and leukocyte count influenced ADP-induced platelet aggregation in multiple assessment points. BMI, concentrations of hemoglobin, glycated hemoglobin, and BNP, hematocrit, adherence to medication, and patient׳s age were found to be independent predictors of high on-treatment ADP-induced platelet aggregation only at a single follow-up visit. Determinants of clopidogrel responsiveness in patients after myocardial infarction change within the long-term therapy. During hospitalization and early after discharge only biological factors affect ADP-induced platelet aggregation, while non-adherence to antiplatelet therapy may be a significant factor in determining clopidogrel non-responsiveness during late follow-up visits.

Does mobilisation of CD34+ stem cells along with VEGF, angiogenin, IL-6, IL-8, and hsCRP levels allow predicting the direction of left ventricular ejection fraction and wall motion score index changes in patients with myocardial infarction?

BACKGROUND: Left ventricular (LV) systolic function is a significant prognostic factor in patients after myocardial infarction (MI). Multiple angiogenic and inflammatory factors are involved in postinfarction LV remodelling process. In addition, CD34+progenitor cells mobilised from bone marrow and tissue niches participate in regeneration of the infarcted myocardium. AIM: To examine relationships between LV ejection fraction (LVEF) and wall motion score index (WMSI) and the number of CD34+ cells and plasma levels of vascular endothelial growth factor (VEGF), angiogenin and such inflammatory factors as interleukin 6 (IL-6), interleukin 8 (IL-8), and high-sensitivity C-reactive protein (hsCRP) in patients with ST-elevation MI (STEMI). METHODS: The study group included 61 patients with STEMI treated with primary percutaneous coronary intervention (PCI)involving bare metal stent implantation. Plasma levels of the evaluated angiogenic and inflammatory factors were measured by flow cytometry at 4 time points (just before PCI, 24 h later, at hospital discharge, and 30 days after STEMI). LVEF and WMSI were measured by echocardiography at hospital discharge, 1 month later, and 6 months later. We compared angiogenic and inflammatory factor levels in patients with no improvement of the LV systolic function during the follow-up (group 1, n = 22)vs. those with improved LV systolic function (group 2, n = 39). RESULTS: No differences in the levels of VEGF, angiogenin, IL-6, IL-8, and hsCRP, and the number of CD34+ cells were observed between the two groups. Despite this, we found significant negative correlations between hsCRP level and LVEF,and positive correlations between hsCRP level and WMSI in both patient groups, but these correlations were much stronger in group 1. We also found a significant negative correlation between WMSI at 6 months and the number of CD34+ cells measured 24 h after PCI. CONCLUSIONS: 1. Evaluation of plasma VEGF, angiogenin, IL-6, IL-8, and hsCRP levels and the number of CD34+ cells at different time points in patients with STEMI did not allow predicting the direction of changes in LVEF and WMSI. 2. Observed significant correlations between hsCRP level and LVEF and WMSI may suggest a harmful effect of inflammation on postinfarction myocardial remodelling. 3. A significant negative correlation between the number of CD34+ and WMSI suggests that increased mobilisation of these cells might have a beneficial effect on systolic function after MI.

Specificity and sensitivity of INI-1 labeling in epithelioid sarcoma. Loss of INI1 expression as a frequent immunohistochemical event in synovial sarcoma.

INI1 antigen is a product of the INI-1/SMARCB1 gene localized on chromosome 22q. It is well known that INI1 gene inactivation or loss of INI1 antigen expression is observed in epithelioid sarcomas; however, there are only few reports concerning specificity and sensitivity of immunohistochemical INI1 labeling as a marker of this neoplasm. That is why we decided to test 99 soft tissue sarcomas for the presence of the INI1 gene product. More specifically, the analyzed group consisted of 33 synovial sarcomas, 14 fibrosarcomas, 8 desmoid tumors, 8 DFSPs, 5 MPNSTs, 9 epithelioid sarcomas, 11 Ewing sarcomas/PNETs, 9 rhabdomyosarcomas and 2 clear cell sarcomas. Additionally, 7 malignant melanomas and 9 adenocarcinomas were included into the study. Positive staining with an antibody against the INI-1 gene product was observed in all studied cases of MPNST, Ewing sarcoma/PNET, rhabdomyosarcoma, malignant melanoma, clear cell sarcoma, and adenocarcinoma. On the contrary, none of 9 epithelioid sarcomas was labeled. The loss of INI1 expression was also detected in 7 (21.2%) synovial sarcomas, confirmed cytogenetically or by FISH. Considering the lack of reaction with INI-1 antibody as a diagnostic test for epithelioid sarcoma we estimated that its sensitivity reached 100% and specificity - 83.5% (p < 0.0001).

[Percutaneous closure of mitral perivalvular leak]. / Przezskórne zamkniecie mitralnego przecieku okolozastawkowego.

Paravalvular leak (PVL) is a complication observed in patients after prosthetic valve replacement. The incidence of PVL is estimated as 2-3%. The cause of PVL may be paravalvular infection, suture continuity disruption, damage of tissues around the annulus or limitation of disc mobility by thrombus or vegetation. The preferable method of treatment of PVL is surgery. Recently, percutaneous closure of PVL became an alternative method. We present a case of successfully completed percutaneous closure of PVL with the use of Amplatzer occluder device in a patient with mitral PVL.

Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first ST-segment elevation myocardial infarction: Preliminary report.

BACKGROUND: Numerous trials have reported on the morning increase in the occurrence of myocardial infarction, stroke and sudden cardiac death. Similarly, enhanced morning platelet aggregation has been observed in healthy individuals and in subjects with coronary artery disease without adequate antiplatelet treatment. The purpose of the study was to assess circadian variation in platelet aggregation in patients with first ST-elevation myocardial infarction (STEMI) treated with primary percutaneous coronary interventions (pPCI) and dual antiplatelet therapy. METHODS: Fifteen consecutive patients (12 men and 3 women) were prospectively recruited into the study. Blood samples were collected at 6.00 a.m., 10.00 a.m., 2.00 p.m. and 7.00 p.m. on the third day of hospitalization. Aggregation in response to arachidonic acid and adenosine diphosphate (ADP) was assessed in the whole blood on a new generation impedance aggregometer. RESULTS: A morning increase of 75% in ADP-dependent platelet aggregation was noted in the study population (p < 0.04). In contrast, we failed to show any significant diurnal variation in arachidonic acid-mediated platelet aggregation. The magnitude of the morning surge in platelet aggregation after ADP stimulation did not correlate with its baseline level. CONCLUSIONS: Increased morning ADP-dependent platelet aggregation persists despite dual antiplatelet therapy in patients with first STEMI undergoing pPCI. The clinical significance of this finding remains to be demonstrated.