Safety and Efficacy of Early SGLT2 Inhibitors Initiation in Diabetic Patients Following Acute Myocardial Infarction, a Retrospective Study.

INTRODUCTION: Sodium-glucose cotransporter- 2 (SGLT2) inhibitors have become a cornerstone in heart failure (HF), Type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) management. In the current retrospective study, we aimed to assess efficacy and safety of SGLT2 inhibitors early following acute myocardial infarction (AMI). METHODS: Patients with T2DM hospitalized for AMI in 2017-2020 were divided according to SGLT2 inhibitors therapy status on discharge (with vs without therapy). Primary outcome was defined as a composite of hospitalizations for HF, recurrent AMI, and cerebrovascular accident (CVA). Secondary outcomes included hospitalizations for any cause, total cumulative number of hospitalizations, and all-cause mortality. RESULTS: A total of 69 patients (mean age 59.2 ± 8.2 years) with AMI discharged with SGLT2 inhibitors were compared to 253 patients (mean age 62.5 ± 9.8) with no SGLT2 inhibitors. During the first year post-AMI, 4 (5.8%) patients in the treatment group and 16 (6.3%) in the control group were hospitalized for CV events (p = 1.0). Patients in the SGLT2 inhibitors group had lower rates of hospitalization for any cause (31.9% vs 47.8%, P = 0.02), with no change in mortality (0% vs 3.6%, P = 0.21). After multivariate regression analysis, only female gender was associated with increased risk for readmission, mainly due to urinary tract infections. No events of diabetic ketoacidosis (DKA) or limb amputation were reported. CONCLUSIONS: We found that early initiation of SGLT2 inhibitors in T2DM patients following AMI is safe and decreases the risk of hospitalization for any cause.

[EVALUATION OF DIFFERENT TIMINGS OF EARLY CARDIAC REHABILITATION AFTER MYOCARDIAL INFARCTION AND EXAMINATION OF DRUG THERAPY BASED ON THE SYNTHESIZED PEPTIDE TO BALANCE THE MITOCHONDRIAL DYNAMICS PROCESSES].

INTRODUCTION: Cardiovascular diseases are the main cause of mortality in the world. Their most common expression is ischemic heart disease (IHD) such as myocardial infarction (MI). Physical rehabilitation is a common practice for IHD patients. Yet, there is no definition of when is the most effective time to start physical rehabilitation. However, it is recommended to start it as soon as possible. There is a growing interest in understanding the relationship between IHD and cardiomyocytes mitochondrial dynamics processes. Mitochondrial imbalance after MI accelerates cardiac damage. Peptide-based drugs are an effective and safe treatment option. AIMS: To examine rehabilitation and peptide intervention post-MI to assess optimal time to start a physical activity and mitochondrial function post-MI. BACKGROUND: Early training as well as peptide treatment will protect the cardiac muscle post-MI from accelerated damage. METHODS: Sixty rats will be divided into 6 groups: Six groups will undergo ischemia-reperfusion (I/R) surgery, by a 30 minute occlusion of their left anterior descending artery (LAD) followed by reperfusion. Three groups will start moderate-intensity exercise training for 8 weeks at different time-points post-MI (3, 7, or 21 days). Another group will be injected with synthetic peptide 5' pre-reperfusion. A sedentary group and a sham group will be used as controls. Results will be assessed by a mitochondrial function test, echocardiography, blood inflammatory and biochemical markers, pressure/volume loops, an exercise test and histology. RESULTS: Improvement of cardiac physiology following exercise training, and mitochondrial treatment will shed light on the preferred timing of cardiac rehabilitation and the mitochondrial damage post-MI.

C-Reactive Protein Can Predict Outcomes in Patients With Takotsubo Syndrome.

Background and Objectives: Takotsubo syndrome (TTS) is a form of reversible cardiomyopathy often preceded by mental or physical stressors and predominantly affects elderly women. Several cardiac and inflammatory biomarkers are involved in the pathogenesis of the disease. We aimed to investigate the correlation of C-reactive protein (CRP) level with left ventricular ejection fraction (LVEF) and clinical outcomes in patients with TTS. Methods: The study included patients with discharge-diagnosis of Takotsubo through 2017-2022 from the cardiology department. Demographic, laboratory, echocardiographic, and clinical outcomes were retrospectively obtained. We investigated the relation between CRP and LVEF, length of stay (LOS), in-hospital complications, and recurrence. Results: A total of 86 patients (93% female, mean age 68.8±12.3 years) were included in the study. The median CRP level was 17.4 (interquartile range [IQR], 6.1-40.1) mg/L, and the mean LVEF was 41.5%, (IQR, 38-50%). Complications occurred in 24 (27.9%) of the patients, and the median LOS was 3 (IQR, 3-5) days. The level of CRP was associated with lower LVEF (r=-0.39, p<0.001), longer hospital stay (r=0.25, p=0.021), and recurrence. There was no correlation between CRP and in-hospital complications. In multivariate logistic regression, poor LVEF was associated with TTS recurrence (odds ratio, 1.22; 95% confidence interval, 1.08-1.37; p=0.001). Using linear regression, only CRP was correlated with longer LOS and lower LVEF (p<0.001). Conclusions: Among patients hospitalized with TTS, CRP level was associated with poor LVEF and prolonged hospital stay but not with in-hospital complications. Poor LVEF was also associated with TTS recurrence.

The Risk of Left Atrial Appendage Thrombus in Patients With Atrial Flutter Versus Atrial Fibrillation.

Objective: Patients with atrial fibrillation (AF) are at increased risk of thromboembolic events originating mainly from left atrial appendage thrombus (LAAT). Patients with atrial flutter (AFL) are treated with anticoagulation based on the same criteria as patients with AF. However, whether patients with AFL have similar thromboembolic risk as AF is unclear. In the current study we aimed to estimate the prevalence of LAAT in patients with AFL undergoing trans-esophageal echocardiography (TEE). Methods/results: We included 438 patients (404 with AF and 34 with AFL) scheduled for TEE to rule out LAAT before cardioversion (patients who reported no or inadequate anticoagulation before cardioversion). Demographic and echocardiographic data were compared between patients with and without LAAT. Despite a similar CHA2DS2-VASC score (3.8 ± 1.3 vs 3.4 ± 1.5 in the AF and AFL groups, respectively, P = .09), LAAT was documented in 12 (2.8%) in the AF group and in no patient in the AFL group (P < .0001). Conclusion: Based on our results and previous studies, it seems reasonable to re-evaluate the need for oral anticoagulation in specific populations with AFL such as those with solitary AFL (without a history of AF episodes) undergoing successful ablation and in those with low CHA2DS2-VASC score.

Complete Transesophageal Assessment of the Aortic Valve Using the Continuity Equation in Equivocal Cases of Aortic Stenosis.

BACKGROUND: The continuity equation (CE) used for evaluating aortic stenosis (AS) is based on values obtained from transthoracic echocardiography (TTE) with the assumption that the left ventricular outflow tract (LVOT) has a circular shape. Transesophageal echocardiography (TEE) may be used for accurate measurement of the LVOT cross-sectional area (CSA). Previous studies have focused on fusion from TEE for LVOT-CSA measurement and TTE for velocity time integrals (VTI) calculations. OBJECTIVES: To assess aortic valve area (AVA) using parameters obtained exclusively from TEE as an alternative approach. METHODS: Thirty patients with equivocal AS based on TTE were evaluated using TEE for further assessment. RESULTS: The mean pressure gradient across the aortic valve (AV) was 38 ± 5.9 and 37.9 ± 7.6 mmHg in TTE and TEE, respectively, P = 0.42. LVOT-CSA was larger in TEE (3.6 ± 0.3 vs. 3.4 ± 0.3 cm2, P = 0.049). VTI over the AVA was similar (98.54 ± 22.8 and 99.52 ± 24.52 cm in TTE and TEE, respectively, P = 0.608), while VTI across the LVOT was higher when measured by TTE (24.06 ± 5.8 vs. 22.03 ± 4.3 cm, P < 0.009). Using the CE, AVA was 0.82 ± 0.3 vs. 0.83 ± 0.17 cm2 in TEE vs. TTE, respectively, P = 0.608. Definitive grading was achieved in all patients (26 patients defined with severe AS and 4 with moderate). CONCLUSIONS: In equivocal cases of AS, full assessment using TEE may be a reliable modality for decision making.

The Role of Extracellular Signal-Regulated Kinase Pathways in Different Models of Cardiac Hypertrophy in Rats.

Cardiac hypertrophy develops following different triggers of pressure or volume overload. In several previous studies, different hypertrophy types were demonstrated following alterations in extracellular signal-regulated kinase (ERK) pathway activation. In the current study, we studied two types of cardiac hypertrophy models in rats: eccentric and concentric hypertrophy. For the eccentric hypertrophy model, iron deficiency anemia caused by a low-iron diet was implemented, while surgical aortic constriction was used to induce aortic stenosis (AS) and concentric cardiac hypertrophy. The hearts were evaluated using echocardiography, histological sections, and scanning electron microscopy. The expression of ERK1/2 was analyzed using Western blot. During the study period, anemic rats developed eccentric hypertrophy characterized by an enlarged left ventricle (LV) cavity cross-sectional area (CSA) (59.9 ± 5.1 mm2 vs. 47 ± 8.1 mm2, p = 0.002), thinner septum (2.1 ± 0.3 mm vs. 2.5 ± 0.2 mm, p < 0.05), and reduced left ventricular ejection fraction (LVEF) (52.6% + 4.7 vs. 60.3% + 2.8, p < 0.05). Rats with AS developed concentric hypertrophy with a thicker septum (2.8 ± 0.6 vs. 2.4 ± 0.1 p < 0.05), increased LV muscle cross-sectional area (79.5 ± 9.33 mm2 vs. 57.9 ± 5.0 mm2, p < 0.001), and increased LVEF (70.3% + 2.8 vs. 60.0% + 2.1, p < 0.05). ERK1/2 expression decreased in the anemic rats and increased in the rats with AS. Nevertheless, the p-ERK and the p-MEK did not change significantly in all the examined models. We concluded that ERK1/2 expression was altered by the type of hypertrophy and the change in LVEF.

The impact of on-site cardiac surgical backup on clinical outcomes of acute coronary syndrome-analysis of the ACSIS national registry.

Background: The availability of advanced technologies for mechanical support in hospitals with on-site cardiac surgery (CS), along with the ability to perform urgent coronary artery bypass graft (CABG) surgery, may result in improved clinical outcomes in patients with acute coronary syndrome (ACS). Methods: We conducted a retrospective analysis of the bi-annually Acute Coronary Syndrome Israeli Survey (ACSIS) registry from the year 2000 to 2020, performed in hospitals with and without CS. Mortality rates and major adverse cardiac and cerebrovascular events (MACCE) rates are reported. We evaluated two periods of the study-early (2000-2010) vs. late (2011-2020). Propensity score matching was performed to reduce bias between the two groups. Results: The study included 16,979 patients (52.3% in the on-site CS group). Patients in the on-site CS group were more likely to undergo percutaneous coronary intervention (PCI), (odds ratio [OR], 1.26 [95% CI, 1.18-1.35]; p < 0.001) and CABG [OR, 1.91 (95%CI, 1.63-2.24); P < 0.001], and patients in hospitals without on-site CS had higher 30-day MACCE [OR, 1.17 (95% CI, 1.07-1.27); p < 0.0005]. Overall, there was no difference in 1-year mortality (hazard ratio [HR], 0.98 [95% CI, 0.89-1.08]; p = 0.71) between the groups. During the late period of the study, patients in the group without on-site CS had lower 30-day mortality [OR, 0.69 (95% CI, 0.49-0.97); P = 0.04], yet with no difference in 1-year mortality [HR, 0.81 (95% CI, 0.65-1.01); p = 0.07]. Conclusions: The availability of on-site CS resulted in variations in treatment modality, yet it did not affect the clinical outcomes of ACS. A trend to a better short-term outcomes was noted in hospitals without CS during the late period of the study, which warrants further investigation.

The safety of sodium-glucose co-transporter 2 inhibitors in patients with left ventricular assist device - a single center experience.

AIMS: Sodium-glucose co-transporter 2 (SGLT2) inhibitors are used increasingly for patients with heart failure or chronic kidney disease to improve cardiac and renal outcomes. The use of these medications in patients with left ventricular assist devices (LVAD) is still limited and lacks evidence regarding the safety profile. In this study, we aimed to report our experience in treating 20 patients, supported by LVAD, with SGLT2 inhibitors. METHODS: We studied the safety profile of SGLT2 inhibitors (dapagliflozin and empagliflozin) in 20 patients (mean age 64.7 ±â€Š12.2 years, 75% male) supported by LVAD as destination therapy. All patients have diabetes mellitus and were prescribed SGLT2 inhibitors for glycemic control. RESULTS: SGLT2 inhibitors were well tolerated with no major adverse events. Few suction events were reported in three patients without the need for pump speed adjustment. There was no change in mean arterial pressure (71.1 ±â€Š5.6 vs. 70.1 ±â€Š4.8 mmHg, P  = 0.063). Modest decline in renal function was observed in six patients within the first weeks after drug initiation. There were no events of diabetic ketoacidosis or limb amputation. CONCLUSION: SGLT2 inhibitors are safe in patients with LVAD and may potentially improve cardiovascular and renal outcomes in this special population.

Downstream Imaging Studies Do Not Significantly Improve Outcome in Most Patients with Chest Pain Who Did Not Reach Their Target Heart Rate on a Stress ECHO Study.

Echocardiographic stress tests are often used to evaluate patients who complain of chest pain. However, some patients fail to reach the target heart rate required for the test to be conclusive (usually defined as 85% of the predicted maximal heart rate based on the patient's age) and are often sent for additional imaging tests, such as myocardial perfusion imaging (MPI) or cardiac computed tomography angiography (CTA). Few studies have evaluated the effectiveness of these additional tests in patients who present with chest pain but did not meet the heart rate requirements for a stress test. The primary objective of the study was to evaluate the efficacy of additional imaging tests for patients who experience chest pain during daily activities but are unable to reach the target heart rate currently required for an echocardiographic stress test. The study group included 415 consecutive patients who underwent a stress echocardiogram, did not achieve their target heart rate, and did not demonstrate abnormal changes during the test. The control group consisted of 415 consecutive patients who did reach their target heart rate and demonstrated no signs of ischemia. Demographic and clinical data, medication use, imaging test results (MPI, CTA, and/or coronary catheterization) and documented cardiac events that occurred during 1 year of follow-up were obtained from the electronic medical records. Of the 415 patients in the study group, 73 (17.6%) were referred to another imaging test within 12 months. Of these 73 patients, 59 underwent MPI and 14 underwent cardiac CTA. In 12 of these patients (16.4%) the test was considered to be abnormal, but only 7 patients (1.7%) subsequently underwent a percutaneous intervention (PCI). In the control group, 28 (6.7%) patients were referred for another imaging test. Of these 28 patients, 14 underwent MPI and 14 underwent cardiac CTA. None of these tests were found to be abnormal, but two patients (0.5%) underwent a PCI (p = 0.2 between groups). There were no deaths during the study period and no patients underwent bypass surgery. The majority of the patients who underwent PCI had additional clinical risk factors (diabetes, hypertension, and/or known coronary artery disease), had taken a beta blocker within 24 h prior to the test, and/or did not reach a heart rate above 78% of their target heart rate. Our study suggests that in most patients with chest pain who do not show ischemic changes on a stress echocardiogram, additional imaging studies can be safely deferred, even if the required target heart rate was not reached. However, in patients with diabetes and/or known coronary disease, those who took a beta blocker 24 h prior to the test, or those who did not achieve a heart rate above 78% of the current target heart rate, additional imaging studies should be considered.

Admission Serum Magnesium Levels Is Associated with Short and Long-Term Clinical Outcomes in COVID-19 Patients.

BACKGROUND: In the face of the global pandemic that the coronavirus disease 2019 (COVID-19) has created, readily available prognostic markers may be of great use. OBJECTIVE: To evaluate the association between serum magnesium (sMg) levels on admission and clinical outcomes in hospitalized COVID-19 patients. METHODS: We retrospectively analyzed all patients admitted to a single tertiary center with a primary de novo diagnosis of COVID-19. Patients were followed for a mean of 10 ± 7 months. Demographic, clinical and laboratory data were collected and compared between five groups of patients according to sMg quintiles on hospital admission. RESULTS: The cohort included 1522 patients (58% male, 69 ± 17 years old). A low sMg level (1st quintile) was associated with higher rates of diabetes and steroid use, whereas a high sMg level (5th quintile) was associated with dyslipidemia, renal dysfunction, higher levels of inflammatory markers and stay in the intensive care unit. All-cause in-hospital and long-term mortality was higher in patients with both low and high sMg levels, compared with mid-range sMg levels (2nd, 3rd and 4th quintiles; 19% and 30% vs. 9.5%, 10.7% and 17.8% and 35% and 45.3% vs. 23%, 26.8% and 27.3% respectively; p < 0.001 for all). After adjusting for significant clinical parameters indicating severe disease and renal dysfunction, only low sMg state was independently associated with increased mortality (HR = 1.57, p < 0.001). CONCLUSIONS: Both low and high sMg levels were associated with increased mortality in a large cohort of hospitalized COVID-19 patients. However, after correction for renal dysfunction and disease severity, only low sMg maintained its prognostic ability.

Sodium-Glucose Co-Transporter 2 Inhibitors in Heart Failure-Current Evidence in Special Populations.

Sodium-glucose co-transporter 2 (SGLT2) inhibitors, originally used for diabetes mellitus, are gaining more popularity for other indications, owing to their positive cardiovascular and renal effects. SGLT2 inhibitors reduce heart failure (HF) hospitalization and improve cardiovascular outcomes in patients with type 2 diabetes. Later, SGLT2 inhibitors were evaluated in patients with HF with reduced ejection fraction (HFREF) and had beneficial effects independent of the presence of diabetes. Recently, reductions in cardiovascular outcomes were also observed in patients with HF with preserved ejection fraction (HFPEF). SGLT2 inhibitors also reduced renal outcomes in patients with chronic kidney disease. Overall, these drugs have an excellent safety profile with a negligible risk of genitourinary tract infections and ketoacidosis. In this review, we discuss the current data on SGLT2 inhibitors in special populations, including patients with acute myocardial infarction, acute HF, right ventricular (RV) failure, left ventricular assist device (LVAD), and type 1 diabetes. We also discuss the potential mechanisms behind the cardiovascular benefits of these medications.

The Role of Stress in Stable Patients with Takotsubo Syndrome-Does the Trigger Matter?

BACKGROUND: Takotsubo syndrome (TTS) is a unique type of reversible cardiomyopathy that predominantly affects elderly women. The role of physical and emotional stress in the pathophysiology of TTS is well established. However, the association between preceding emotional triggers and clinical outcomes in stable patients has not yet been fully investigated. We aimed to investigate the association between emotional triggers before symptom onset and clinical outcomes in stable patients with TTS. METHODS: This is a retrospective cohort study based on the data of patients with ICD-9 discharge diagnosis of TTS between 2017 and 2022. Patients were divided into two groups: with and without obvious emotional trigger before symptom onset. Demographic, laboratory, echocardiographic, and clinical outcomes were obtained and compared between the two groups. RESULTS: We included 86 patients (93% were women, mean age 68.8 ± 12.3 years). Of them, 64 (74.4%) reported an emotional trigger before symptom onset. Patients with a previous emotional trigger had a longer hospital stay (4.3 + 2.0 days vs. 3.0 + 1.4, p = 0.002) with no difference in in-hospital complications (32.8% vs. 13.6%, p = 0.069), with no difference in 30-day mortality, readmissions, or recurrence rate between the groups. CONCLUSIONS: Patients with TTS related to an emotional trigger may represent a different population from patients without a preceding trigger by having more symptomatic disease and longer hospital stay, yet with no difference in the 30-day outcomes.

The Molecular Effects of SGLT2i Empagliflozin on the Autophagy Pathway in Diabetes Mellitus Type 2 and Its Complications.

Background: Type 2 diabetes mellitus (T2DM), especially hyperglycemia, is associated with increased glucose cell toxicity and oxidative stress that can lead to irreversible damage in the kidney such as diabetic nephropathy (DN). Autophagy plays a key role in the degradation of damaged intracellular proteins in order to maintain intracellular homeostasis and cell integrity. The disturbance of autophagy is involved in the pathogenesis of diabetic nephropathy. We aim to investigate the molecular effect of sodium-glucose transporter 2 inhibitor (SGLT2i) on the expression of ATG5 and its downstream collaborator LC3-II in diabetic nice model. Material and Methods. We used eight weeks old male mice: twenty C57BL/6 wild type (C57BL/6), twenty BTBR ob/ob (DM), and twenty BTBR ob/ob that were treated with empagliflozin (DM+EMPA), FDA approved SGLT2i. Lysate from murine renal cortex was analyzed by Western blot and immunohistochemistry. ATG5, LC3B, and fibronectin expression were analyzed in murine kidney tissues. All mice were sacrificed 13 weeks after the beginning of the experiment. Results: Histological and Western blot analyses reveal decrease ATG5, LC3-II, and fibronectin levels at renal specimens taken from DM mice. EMPA treatment reduced T2DM mice body weight and blood glucose and increased urine glucose. Further, it upregulated all of the abovementioned proteins. Conclusions: Hyperglycemia reduces LC3-II and ATG5 protein levels which contribute to deficiencies in the autophagy process, with development and progression of DN. SGLT2i significantly reduces progression of DN and onset of end-stage renal disease in T2DM patients, probably through its effect on autophagy.

Peripheral artery disease, abnormal ankle-brachial index, and prognosis in patients with acute coronary syndrome.

Objectives: Ankle-brachial index (ABI) is an independent prognostic marker of cardiovascular events among patients with coronary artery disease (CAD). We aimed to investigate the outcome of patients hospitalized with acute coronary syndrome (ACS) and abnormal ABI. Approach and results: ABI was prospectively measured in 1,047 patients hospitalized due to ACS, who were stratified into three groups, namely, those with clinical peripheral artery disease (PAD) (N = 132), those without clinical PAD but with abnormal (< 0.9) ABI (subclinical PAD; N = 148), and those without clinical PAD with normal ABI (no PAD; N = 767). Patients were prospectively followed for 30-day major adverse cardiovascular event (MACE) and 1-year all-cause mortality. The mean age was 64 years. There was a significant gradual increase throughout the three groups in age, i.e., the incidence of prior stroke, diabetes mellitus, and hypertension (p for trend = 0.001 for all). The in-hospital course showed a gradual rise in the incidence of complications with an increase in heart failure [2.5, 6.1, and 9.2%, (p for trend = 0.001)] and acute kidney injury [2, 4.1, and 11.5%, (p for trend = 0.001)]. At day 30, there was a stepwise increase in MACE, such that patients without PAD had the lowest rate, followed by subclinical and clinical PADs (3.5, 6.8, and 8.1%, respectively, p for trend = 0.009). Similarly, there was a significant increase in 1-year mortality from 3.4% in patients without PAD, through 6.8% in those with subclinical PAD, to 15.2% in those with clinical PAD (p for trend = 0.001). Conclusion: Subclinical PAD is associated with poor outcomes in patients with ACS, suggesting that routine ABI screening could carry important prognostic significance in these patients regardless of PAD symptoms.

Paraoxonase 1 hydrolysis of EPA-derived lactone impairs endothelial-mediated vasodilation.

Human serum paraoxonase-1 (PON1) is a lactonase that plays a significant role in anti-atherosclerotic high-density lipoprotein (HDL) activity. PON1 is also localized in endothelial cell membranes, where it is enzymatically active and regulates endothelial signals. PON1 has a high specificity for lipophilic lactones and has been shown to hydrolyze and regulate lactone lipid mediators derived from arachidonic polyunsaturated fatty acids (PUFA). Previously, we showed that an arachidonic acid lactone metabolite (AA-L) dose-dependently dilates PON1 gene deletion (PON1KO) mouse mesenteric arteries significantly more than wild-type arteries. In contrast, preincubation with HDL or rePON1 reduced AA-L-dependent vasodilation. Recently we showed that an additional δ-lactone metabolite derived from the eicosapentaenoic acid lactone, 5,6-δ-DiHETE lactone (EPA-L) reduced blood pressure by dilating microvessels of hypertensive rats. However, whether PON1 regulates the activity of the EPA-L lipid mediator is unknown. AIM: To demonstrate that PON1 hydrolyzes EPA-L and to reveal the effect of this hydrolysis on endothelial-dependent vascular dilation. METHODS AND RESULTS: In vascular reactivity experiments, EPA-L dose-dependently dilated PON1KO mouse mesenteric arteries significantly more than wild-type mesenteric arteries. This dilation was not affected by nitric oxide inhibition. PON1 impaired the cellular calcium increase mediated by EPA-L in endothelial cells, though this impairment decreased with PON1 internalization to the cell. CONCLUSION: These findings support that PUFA-lactones are physiological substrates of PON1, and that PON1 activity in the endothelial membrane affects the dilation of microvessels that is induced by these endothelial-derived hyperpolarizing PUFA-lactones.

The Prognostic Value of Natriuretic Peptides in Stable Patients with Suspected Acute Myocarditis: A Retrospective Study.

Risk stratification in acute myocarditis is based on the clinical signs of heart failure, the degree of cardiac dysfunction, and the findings in cardiac magnetic resonance (CMR). The aim of the current study is to examine the prognostic yield of the natriuretic peptide N-terminal-pro hormone Brain Natriuretic Peptide (NT-proBNP) and C-reactive protein (CRP) in acute myocarditis among patients with preserved/mildly reduced left ventricular ejection fraction (LVEF). We retrospectively analyzed 59 patients (median age 28 years, 76% males) with ICD-9 discharge diagnosis of acute myocarditis. Basic characteristics, echocardiographic, and laboratory parameters were obtained from computerized files. The median length of stay was 3, (IQR 2−5) days, and the median LVEF was 48% (IQR, 54−62%). High levels of NT-proBNP and CRP were associated with increased length of stay (r = 0.57, p < 0.001; r = 0.4 p = 0.001, respectively), while troponin level was not (r = 0.068, p = 0.61). During the index hospitalization, complications occurred in 14 (23.7%) patients. High NT-proBNP and CRP levels were associated with complications (p < 0.001, and p = 0.001, respectively), while troponin level was not (p = 0.452). In conclusion, routine measurement of NT-proBNP and CRP are preferred over troponin for risk stratification in hemodynamically stable myocarditis.

Peripheral Arterial Disease in Patients With Acute Coronary Syndrome: Results From a Large Real-World Registry.

BACKGROUND: Limited data exist regarding the significance of peripheral arterial disease (PAD) in patients with acute coronary syndrome (ACS). METHODS: We evaluated 16,922 consecutive ACS patients who were prospectively included in a national ACS registry. The co-primary endpoint included 30 days major adverse cardiovascular event (MACE) (re-infarction, stroke, and/or cardiovascular death) and 1-year mortality. RESULTS: PAD patients were older (70±11 vs 63±13; p<0.01), male predominance (80% vs 77%; p=0.01), and more likely to sustain prior cardiovascular events. PAD patients were less likely to undergo coronary angiography (69% vs 83%; p<0.001) and revascularisation (80% vs 86%; p<0.001). Patients with PAD were more likely to sustain 30-day MACE (22% vs 14%; p<0.001) and mortality (10% vs 4.4%; p<0.001), as well as re-hospitalisation (23% vs 19%; p=0.001). After adjusting for potential confounders, PAD remained an independent predictor of 30-day MACE (odds ratio [OR], 1.6 [95% confidence interval (CI), 1.24-2.06]). Patients with compared to those without PAD had 2.5 times higher 1-year mortality rate (22% vs 9%; p<0.001). Co-existence of PAD remained an independent predictor of 1-year mortality after adjustment for potential confounders by multivariable regression analysis (OR, 1.62; 95% CI, 1.4-1.9). PAD was associated with a significant higher 1-year mortality rate across numerous sub-groups of patients including type of myocardial infarction (ST-elevation myocardial infarction vs non-ST-elevation myocardial infarction), and whether the patient underwent revascularisation. CONCLUSIONS: Acute coronary syndrome with concomitant PAD represents a high-risk subgroup that warrants special attention and a more tailored approach.

Cardiac assessment accuracy by students using palm-held ultrasound compared to physical examination by skilled cardiologists: a pilot study with a single medical student.

BACKGROUND: Despite the inherent limitations of the traditional cardiac physical examination (PE), it has not yet been replaced by a more accurate method. METHODS: We hypothesized that a single medical student, following a brief training (two academic hours) with the PHU, will better identify abnormal findings including significant valvular diseases, pericardial effusion and reduced LV function, as compared to PE performed by senior cardiologists and cardiology fellows. Transthoracic echocardiogram (TTE) served as a 'gold standard'. RESULTS: Seventy-seven patients underwent TTE, of them 64 had an abnormal finding. PE identified 34 patients with an abnormal finding compared to 52 identified by PHU (p < 0.05). Ejection fraction (EF) below 50% was found in 35 patients on TTE, compared to only 15 and 6 patients by PE and PHU, respectively (p < 0.05). There was no difference in valvular dysfunction diagnosis detected by PE and medical students using PHU. The overall accuracy of PHU compared to TTE was 87%, with a specificity of 94% and sensitivity of 64% (the low sensitivity was driven mainly by EF assessment), whereas the accuracy of PE was 91%, specificity 91% and sensitivity 38% (again driven by poor EF assessment). CONCLUSIONS: Cardiac evaluation using PHU by a single medical student was able to demonstrate similar accuracy as PE done by cardiac specialists or cardiology fellows. The study topic should be validated in future studies with more medical students with a very brief training of cardiac ultrasound.

Stress-Induced Cardiomyopathy-Considerations for Diagnosis and Management during the COVID-19 Pandemic.

The novel coronavirus disease 2019 (COVID-19) is associated with several cardiovascular manifestations including myocardial injury, myocarditis, arrhythmia, and pulmonary embolism. Rare cases of stress-induced cardiomyopathy, or takotsubo syndrome have also been reported during the acute infection, and secondary to stress following lockdown and self-isolation. Diagnosis in the setting of the acute infection is challenging since conventional imaging modalities such as transthoracic echocardiography and coronary angiography should be restricted to minimize physician-patient contact until the patients is tested negative for COVID-19. The use of point of care hand-held ultrasound is appropriate for this purpose. The overall course of the disease seems to be similar to takotsubo in the general population. Physicians should be familiar with the clinical presentation, possible complications, and management of takotsubo during COVID-19 outbreak. Here, we review the special considerations in the diagnosis and management of takotsubo syndrome during the current pandemic.