Missed Opportunities in Implementation and Optimization of Lipid-Lowering Therapies in Very-High-Risk Patients Presenting with ST-Segment Elevation Myocardial Infarction.

The aim of this retrospective study was to provide real-world data on lipid-lowering therapy (LLT) implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in an ST-segment elevation myocardial infarction (STEMI) population, with a focus on very-high-risk patients according to European guidelines criteria. METHODS: Included were all STEMI patients with available LDL-C and total cholesterol treated at a large tertiary center in Salzburg, Austria, 2018-2020 (n = 910), with stratification into very-high-risk cohorts. Analysis was descriptive, with variables reported as number, percentages, median, and interquartile range. RESULTS: Among patients with prior LLT use, statin monotherapy predominated, 5.3% were using high-intensity statins, 1.2% were using combined ezetimibe therapy, and none were taking PCSK9 inhibitors at the time of STEMI. In very-high-risk secondary prevention cohorts, LLT optimization was alarmingly low: 8-22% of patients were taking high-intensity statins, just 0-6% combined with ezetimibe. Depending on the very-high-risk cohort, 27-45% of secondary prevention patients and 58-73% of primary prevention patients were not taking any LLTs, although 19-60% were actively taking/prescribed medications for hypertension and/or diabetes mellitus. Corresponding LDL-C target achievement in all very-high-risk cohorts was poor: <22% of patients had LDL-C values < 55 mg/dL at the time of STEMI. CONCLUSION: Severe shortcomings in LLT implementation and optimization, and LDL-C target achievement, were observed in the total STEMI population and across all very-high-risk cohorts, attributable in part to deficits in care delivery.

Early beta-blocker therapy improves in-hospital mortality of patients with non-ST-segment elevation myocardial infarction - a meta-analysis.

BACKGROUND: Although current guidelines endorse early beta-blocker therapy in stable patients with STEMI, there is no clear recommendation on the early use of these drugs in patients with NSTEMI. METHODS: Literature search was conducted by 3 independent researchers using PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS. Studies were eligible if (P) patients included were ≥ 18 years of age and had non-ST-segment elevation myocardial infarction (NSTEMI), (I) early (<24 h) treatment with intravenous or oral beta-blockers was compared to (C) no treatment with beta-blockers and data on (O) in-hospital mortality and/or in-hospital cardiogenic shock were depicted. Odds ratios and 95% confidence intervals were calculated using random effects models with the Mantel-Haenszel method. The Hartung-Knapp-Sidik-Jonkman method was used as estimator for τ2. RESULTS: 977 records were screened for eligibility, which led to the inclusion of 4 retrospective, nonrandomized, observational cohort studies comprising a total of N = 184,951 patients. After pooling of the effect sizes, early therapy with beta-blockers resulted in a reduction of in-hospital mortality (OR 0.43 [0.36-0.51], p = 0.0022) despite no significant effect on the prevalence of cardiogenic shock (OR 0.36 [0.07-1.91], p = 0.1196). CONCLUSION: Early treatment with beta-blockers was associated with an attenuation of in-hospital mortality despite no increase in cardiogenic shock. Thus, early therapy with these drugs could elicit beneficial effects on top of reperfusion therapy, similar to the effects seen in STEMI-patients. The low number of studies (k = 4) has to be considered when interpreting the findings of this analysis.

Tei Index Complements Conventional Echocardiographic Parameters in Diagnostic Workup of Suspected Takotsubo Syndrome.

BACKGROUND: Tei index (TI) is a combined myocardial performance index for overall cardiac function, the sensitivity of which seems to be better than that of systolic and diastolic parameters alone. Evidence for TI in the context of Takotsubo syndrome (TTS) is currently limited, which is why we chose to investigate this parameter in affected patients. SUBJECTS AND METHODS: Patients with TTS (n = 51), acute coronary syndrome (ACS; n = 29), and controls (n = 58) were retrospectively investigated. Laboratory and echocardiographic parameters including TI were analyzed for their ability to discriminate TTS in the total study cohort. RESULTS: TI was the highest, and thus most pathological, in patients with TTS (median 0.516 vs. ACS: 0.355 vs. control: 0.313, p < 0.0001) and showed the best discriminatory ability for TTS (AUC: 0.836, p < 0.0001). A cut-off for diagnosis of TTS was calculated at ≥0.418 (specificity: 83.5% and sensitivity: 74.0%) by means of the Youden index. CONCLUSION: The discriminatory ability of TI was better than that of other echocardiographic parameters such as LV systolic function. Due to the simple, fast, and inexpensive way of calculating TI, diagnostic workup with conventional parameters could be complemented by TI in patients with suspected TTS.

Tei Index Is a Useful Adjunctive Tool in the Diagnostic Workup of Patients with Acute Myocarditis.

Background: Tei index (TI) is a combined myocardial performance index, which was found to be more sensitive for overall cardiac dysfunction than systolic or diastolic parameters alone. Currently, there is only limited evidence for this measure in the context of myocarditis. Thus, TI could add additional benefits to conventional diagnostic workup. Methods: TI of patients with myocarditis (n = 40), acute coronary syndrome (n = 29) and controls (n = 50) was retrospectively analyzed concerning its discriminatory ability for myocarditis. Results: TI was most pathological in patients with myocarditis (median 0.41 vs. 0.35 vs. 0.31, p < 0.0001). Its discriminatory ability was better than that of EF or E/e' (AUCs: TI: 0.71, p < 0.0001; EF: 0.57, p = 0.112; E/e': 0.64, p = 0.983), which was also verified in logistic regression analysis (B(SE) = 0.81(0.23), p = 0.0004). The association of TI with myocarditis remained significant even after correction for confounders in propensity score weighted analysis. Conclusions: The TI showed a better discriminatory ability for myocarditis than conventional echocardiographic parameters. Since TI is easily conducted, it might be a helpful adjunctive tool to supplement conventional diagnostic modalities in patients with suspected myocarditis.

A Novel Clinical Score for Differential Diagnosis Between Acute Myocarditis and Acute Coronary Syndrome - The SAlzburg MYocarditis (SAMY) Score.

Background: Acute myocarditis and acute coronary syndrome (ACS) are important differential diagnoses in patients with new-onset chest pain. To date, no clinical score exists to support the differentiation between these two diseases. The aim of this study was to develop such a score to aid the physician in scenarios where discrimination between myocarditis and ACS appears difficult. Materials and Methods: Patients with ACS (n = 233) and acute myocarditis (n = 123) were retrospectively enrolled. Least absolute shrinkage and selection operator (LASSO) regression was conducted to identify parameters associated with the highest or least probability for acute myocarditis. Logistic regression was conducted using the identified parameters and score points for each level of the predictors were calculated. Cutoffs for the prediction of myocarditis were calculated. Validation was conducted in a separate cohort of 90 patients. Results: A score for prediction of acute myocarditis was calculated using six parameters [age, previous infection, hyperlipidemia, hypertension, C-reactive protein (CRP), and leukocyte count]. Logistic regression analysis showed a significant association between total score points and the presence of myocarditis (B = 0.9078, p < 0.0001). Cutoff #1 for the prediction of myocarditis was calculated at ≥ 4 (Sens.: 90.3%, Spec.: 93.1%; 46.3% predicted probability for acute myocarditis), cutoff #2 was calculated at ≥ 7 (Sens.: 73.1%, Spec.: > 99.9%; 92.9% pred. prob.). Validation showed good discrimination [area under the curve (AUC) = 0.935] and calibration of the score. Conclusion: Our clinical score showed good discrimination and calibration for differentiating patients with acute myocarditis and ACS. Thus, it could support the differential diagnosis between these two disease entities and could facilitate clinical decisions in affected patients.

From Streptococcal Pharyngitis/Tonsillitis to Myocarditis: A Systematic Review.

(1) Background: Myocarditis following group A streptococcal pharyngitis and tonsillitis is a relatively rare medical condition. The aim of this systematic review was to identify specific ECG changes, laboratory parameters and signs, and symptoms associated with this disease. (2) Methods: A systematic literature review was performed in concordance with the current PRISMA guidelines, including the databases PubMed/MEDLINE, Web of Science, CDSR, CENTRAL, CCAs, EBM Reviews, and LILACS. Articles were included if they covered myocarditis after streptococcal pharyngitis/tonsillitis in humans. Exclusion criteria were rheumatic, autoimmune, or toxic myocarditis. (3) Results: Patients that developed myocarditis after group A streptococcal throat infection frequently presented with chest pain, elevated cardiac markers, and ST-segment elevations, making it a condition that shows more similarities to acute coronary syndrome than viral myocarditis. (4) Conclusions: Myocarditis after streptococcal pharyngitis and/or tonsillitis is a rather infrequently described disease; however, it is necessary to consider this condition when investigating streptococcal sore throat because it can be associated with severe adverse events for the individual patient.

Differences of Hemogram Parameters and Their Ratios among Patients with Takotsubo Syndrome, Acute Coronary Syndrome and Healthy Individuals.

Introduction: Takotsubo cardiomyopathy (TTC) and acute coronary syndrome (ACS) are clinically indistinguishable from each other. Although therapeutically redundant, coronary angiography remains indispensable for differential diagnosis. Methods: In our study, we compared hemogram parameters and their ratios in 103 patients presenting with undiagnosed chest pain. Blood was drawn at baseline in 40 patients with TTC, 63 patients with ACS, and 68 healthy controls ((Ctrl) no coronary artery disease or signs of heart failure). Results: Peripheral lymphocyte counts were significantly depressed in TTC and ACS patients when compared to the Ctrl. Consequently, all three investigated hemogram ratios were significantly elevated in patients with ACS or TTC (NLR: TTC: median 3.20 vs. ACS: median 3.82 vs. Ctrl: median 2.10, p < 0.0001; BLR: median 0.02 vs. ACS: median 0.00 vs. Ctrl: median 0.00, p < 0.0001; MLR: median 0.37 vs. ACS: median 0.44 vs. Ctrl: median 0.28, p < 0.0001). Of note, BLR was only significantly elevated in patients with TTC, and not in patients with ACS (ACS vs. Ctrl p = 0.183). Conclusion: Basophil count and BLR are significantly increased in TTC patients when compared to ACS and may, therefore, be helpful in the distinction of TTC from ACS. Whereas NLR might be useful to differentiate ACS from controls. Elevated basophil counts and BLR in TTC patients are interesting findings and may confirm speculations about the partly unexplained pathophysiology.

Intranasal application of adeno-associated viruses: a systematic review.

Adeno-associated viruses (AAVs) represent some of the most commonly employed vectors for targeted gene delivery and their extensive study has resulted in the approval of multiple gene therapies to treat human diseases. The intranasal route of vector application in gene therapy offers several advantages over traditional ways of administration. In addition to targeting local tissue like the olfactory epithelium, it provides minimally invasive access to various organ systems, including the central nervous system and the respiratory tract. Through a systematic literature review, a total of 53 articles that investigated the intranasal application of AAVs were identified, included, and summarized in this manuscript. Within these studies, AAV-based gene therapy was mainly investigated for its application in various infectious, pulmonary, or neurologic and/or psychiatric diseases. This review gives a comprehensive overview of the current technological state of the art regarding the intranasal application of AAVs for gene transfer and discusses remaining hurdles, which still have to be resolved before this approach can effectively be implemented in the routine clinical setting.

Treatment with Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) Does Not Affect Outcome in Patients with Acute Myocarditis or Myopericarditis.

Background: Previous animal studies reported an association of non-steroidal anti-inflammatory drugs (NSAIDs) with adverse outcomes in acute myocarditis, which is why these drugs are currently not recommended in affected patients. In this retrospective case-control study, we sought to investigate the effects of NSAID treatment in patients with acute myocarditis and myopericarditis to complement the available evidence. Method: A total of 114 patients with acute myocarditis were retrospectively enrolled. Demographical, clinical and laboratory data were extracted from hospital records. Patients who received NSAIDs (n = 39, 34.2%) were compared to controls. Follow-up on all-cause mortality was acquired for two years. Propensity score matching was additionally conducted to account for covariate imbalances between groups. Results: Treatment with NSAIDs was neither associated with a worse outcome (p = 0.115) nor with significant differences in left ventricular systolic function (p = 0.228) or in-hospital complications (p = 0.507). Conclusion: Treatment with NSAIDs was not associated with adverse outcomes in our study cohort. Together with the findings of previous studies, our results indicate that these drugs could be safely administered in patients with myocarditis and myopericarditis.

Time to abandon ampicillin plus gentamicin in favour of ampicillin plus ceftriaxone in Enterococcus faecalis infective endocarditis? A meta-analysis of comparative trials.

BACKGROUND: Current guidelines recommend either ampicillin plus ceftriaxone (AC) or amoxicillin/ampicillin plus gentamicin (AG) with an equivalent class IB recommendation in Enterococcus faecalis endocarditis. However, previous observational studies suggest that AC might be favourable in terms of adverse events. OBJECTIVES: To investigate whether AC is non-inferior to AG, and if it is associated with less adverse events. METHODS: In June 2021, a systematic literature search using the databases PubMed/MEDLINE, CDSR, CENTRAL, CCAs, EBM Reviews, Web of Science and LILACS was conducted by two independent reviewers. Studies were considered eligible if (P) patients included were ≥ 18 years of age and had IE with E. faecalis, (I) treatment with AC was compared to (C) treatment with AG and (O) outcomes on in-hospital mortality, nephrotoxicity and adverse events requiring drug withdrawal were reported. Odds ratios and 95% confidence intervals were calculated using random-effects models with the Mantel-Haenszel method, the Sidik-Jonkman estimator for τ2 and the Hartung-Knapp adjustment. RESULTS: Treatment with AC was non-inferior to AG, as depicted by no significant differences in-hospital mortality, 3-month mortality, relapses or treatment failure. Furthermore, AC was associated with a lower prevalence of nephrotoxicity (OR 0.45 [0.26-0.77], p = 0.0182) and drug withdrawal due to adverse events (OR 0.11 [0.03-0.46], p = 0.0160) than AG. CONCLUSIONS: Treatment with AC was non-inferior to treatment with AG, and it was associated with a reduced prevalence of nephrotoxicity and drug withdrawal due to adverse events. Thus, combination therapy with AC appears favourable over AG in patients with E. faecalis IE.

Biological Sex and Its Impact on Clinical Characteristics in Patients Presenting with Myocarditis.

INTRODUCTION: Biological sex has a paramount influence on the pathophysiology of diseases, and thus on clinical presentation. In this study, we provide a comprehensive analysis of sex-specific differences in patients with myocarditis. MATERIALS AND METHODS: Patients with myocarditis who were admitted to our study center in the time-period of 2009-2019 were retrospectively enrolled in this study. Clinical data, laboratory parameters, and measurements from transthoracic echocardiography were extracted from hospital records. Follow-up was acquired for 2 years after admission. RESULTS: Two hundred twenty-four patients with myocarditis were enrolled in this study. Of these, 78% were men and 22% women. Female patients were older (median 50 years vs. 35 years, p < 0.0001), had a higher prevalence of respiratory tract infections, and had less frequently ST-segment elevations on electrocardiogram (ECG) (28% vs. 59%, p = 0.003). Furthermore, C-reactive protein was lower in women (median 0.60 mg/dL vs. 3.90 mg/dL, p < 0.0001), but showed a less pronounced decrease within 3 days when compared to men (fold-change 1.00 vs. 0.80, p = 0.002). Cardiac magnetic resonance imaging was conducted less often in women, whereas time to coronary angiography was significantly longer. We found no difference in left ventricular systolic function or all-cause-mortality between the 2 sexes. CONCLUSION: We observed sex-specific differences in laboratory parameters, abnormalities on ECG, and diagnostic procedures conducted in patients with myocarditis. Understanding these differences, both at the cellular level and in regard to the clinical presentation of patients, could be helpful in the diagnosis and treatment of this disease, and could further expand our understanding of its pathophysiology.

Neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio predict length of hospital stay in myocarditis.

Neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte ratio (MLR) are associated with the severity of various diseases. The aim of this study was to demonstrate the relationship of NLR and MLR with the severity of myocarditis. 202 consecutive patients with myocarditis were retrospectively enrolled in this study. Laboratory parameters and clinical data were extracted from hospital records and discharge letters. Median NLR was 2.48 (IQR 1.55-4.58) and median MLR was 0.42 (IQR 0.39-0.58). NLR and MLR correlated with HF, CRP and leukocyte count, MLR further correlated inversely with LV systolic function (rs = - 0.379, p = 0.030). Both ratios correlated better with length of hospital stay (NLR: rs = 0.435, p = 0.003; MLR: rs = 0.534, p < 0.0001) than CRP, leukocyte count, IL-6 or procalcitonin. AUCs for the prediction of prolonged hospital stay (NLR = 0.75, MLR = 0.80), and optimal cut-offs therefor were calculated. Patients who had in-hospital complications showed a higher NLR, however, this remained statistically insignificant. NLR and MLR correlated with the length of stay, as well as with several clinical and laboratory parameters in patients with myocarditis. Since white blood cell differentials are relatively easy and fast to perform, both ratios could facilitate further risk stratification in affected patients.