Implementation of risk-based lipid-lowering therapies in older (age ≥ 65 years) and very-old adults (age ≥ 75 years) with ischemic heart disease in the greater Salzburg region.

Introduction: European guidelines recommend the implementation of lipid-lowering therapies (LLTs) in adults (≥ 65 years) with established atherosclerotic cardiovascular disease (ASCVD) and for risk-based primary prevention in older adults (≤ 75 years), yet their use in very-old adults (> 75 years) is controversial, discretionary, and oriented on the presence of risk factors. The aim of this retrospective study is to assess guideline-directed LLT implementation and low-density lipoprotein cholesterol (LDL-C) target achievement in high-/very-high-risk older/very-old adults (65-74 and ≥ 75 years) at presentation for ST-segment elevation myocardial infarction (STEMI) and also to assess evidence-based care delivery to older adults in our region. Methods: All STEMI patients with available LDL-C and total cholesterol presenting for treatment at a large tertiary center in Salzburg, Austria, 2018-2020, were screened (n = 910). High-risk/very-high-risk patients (n = 369) were classified according to European guidelines criteria and divided into cohorts by age: < 65 years (n = 152), 65-74 years (n = 104), and ≥ 75 years (n = 113). Results: Despite being at high-/very-high-risk, prior LLT use was < 40% in the total cohort, with no significant difference by age. Statin monotherapy predominated; 20%-23% of older/very-old adults in the entire cohort were using low-/moderate-intensity stains, 11%-13% were using high-intensity statins, 4% were on ezetimibe therapy, and none were taking proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. In the secondary prevention cohort, 53% of older/very-old patients used prior LLTs. Significantly higher percentages of older/oldest ASCVD patients (43% and 49%) met LDL-C targets < 70 mg/dL compared to patients < 65 years (29%; p = 0.033), although just 22% and 30% of these older groups attained stricter LDL-C targets of < 55 mg/dL. Low LLT uptake (16%) among older adults aged 64-74 years for primary prevention resulted in 17% and 10% attainment of risk-based LDL-C targets < 70 mg/dL and < 55 mg/dL, respectively. Oldest adults (≥ 75 years) in both primary and secondary prevention groups more often met risk-based targets than older and younger adults, despite predominantly receiving low-/moderate-intensity statin monotherapy. Conclusion: Secondary prevention was sub-optimal in our region. Less than half of older/very-old adults with established ASCVD met LDL-C targets at the time of STEMI, suggesting severe care-delivery deficits in LLT implementation. Shortcomings in initiation of risk-based LLTs were also observed among high-/very-high-risk primary prevention patients < 75 years, with the achievement of risk-based LDL-C targets in 10%-48% of these patients.

Deciphering the Role of microRNAs: Unveiling Clinical Biomarkers and Therapeutic Avenues in Atrial Fibrillation and Associated Stroke-A Systematic Review.

MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression by binding to target messenger RNAs (mRNAs). miRNAs have been implicated in a variety of cardiovascular and neurological diseases, such as myocardial infarction, cardiomyopathies of various geneses, rhythmological diseases, neurodegenerative illnesses and strokes. Numerous studies have focused on the expression of miRNA patterns with respect to atrial fibrillation (AF) or acute ischemic stroke (AIS) However, only a few studies have addressed the expression pattern of miRNAs in patients with AF and AIS in order to provide not only preventive information but also to identify therapeutic potentials. Therefore, the aim of this review is to summarize 18 existing manuscripts that have dealt with this combined topic of AF and associated AIS in detail and to shed light on the most frequently mentioned miRNAs-1, -19, -21, -145 and -146 with regard to their molecular mechanisms and targets on both the heart and the brain. From this, possible diagnostic and therapeutic consequences for the future could be derived.

Methods to predict heart failure in diabetes patients.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) is one of the leading causes of cardiovascular disease and powerful predictor for new-onset heart failure (HF). AREAS COVERED: We focus on the relevant literature covering evidence of risk stratification based on imaging predictors and circulating biomarkers to optimize approaches to preventing HF in DM patients. EXPERT OPINION: Multiple diagnostic algorithms based on echocardiographic parameters of cardiac remodeling including global longitudinal strain/strain rate are likely to be promising approach to justify individuals at higher risk of incident HF. Signature of cardiometabolic status may justify HF risk among T2DM individuals with low levels of natriuretic peptides, which preserve their significance in HF with clinical presentation. However, diagnostic and predictive values of conventional guideline-directed biomarker HF strategy may be non-optimal in patients with obesity and T2DM. Alternative biomarkers affecting cardiac fibrosis, inflammation, myopathy, and adipose tissue dysfunction are plausible tools for improving accuracy natriuretic peptides among T2DM patients at higher HF risk. In summary, risk identification and management of the patients with T2DM with established HF require conventional biomarkers monitoring, while the role of alternative biomarker approach among patients with multiple CV and metabolic risk factors appears to be plausible tool for improving clinical outcomes.

Radiological Parameters for the Detection of Pulmonary Hypertension in Severe Aortic Valve Stenosis and Their Influence on Mortality: Does Sex Matter?

Background: Echocardiography has long been established as the primary noninvasive method for diagnosing pulmonary hypertension (PH) prior to transcatheter aortic valve replacement (TAVR) in patients with severe aortic valve stenosis (AS). In recent years, radiological methods for diagnosing PH have been investigated. Measurements such as the computed tomography angiography (CTA)-derived pulmonary artery (PA) diameter and PA diameter/body surface area (PA/BSA) have shown promising results regarding their diagnostic strength. However, it has yet to be determined if a patient's sex has any impact on the effectiveness of these diagnostic measurements. Methods: In all, 271 patients (51.3% male, mean age 82.6 ± 4.8 years) with severe AS undergoing TAVR were separated into male and female groups. The cut-off values for the diagnosis of PH were calculated for the CTA-derived PA diameter and PA/BSA based on different systolic pulmonal artery pressure values (40-45-50 mmHg). Patients were then subclassified according to measurements above or below these PA diameters and PA/BSA cut-off values. A PA diameter ≥29.5 mm and PA/BSA ≥ 15.7 mm/m2 qualified for PH. The 1-5 year survival rate in these cohorts was further analyzed. Results: Patients with a PA diameter ≥29.5 mm showed a significantly higher 1 year mortality rate (p = 0.014). This observation could only be confirmed for the male sex (p = 0.018) and not for the female sex (p = 0.492). As for the PA/BSA, in patients over the cut-off value, no significant increase in mortality was noted in the overall cohort. However, the male patients showed increased 3 year (p = 0.048) and 5 year mortality rates (p = 0.033). Conclusions: The CTA-obtained PA diameter and PA/BSA are both useful in the diagnosis of PH and mortality risk stratification in patients with severe AS undergoing TAVR, especially in males. Male patients with PA ≥ 29.5 mm or PA/BSA ≥ 15.7 mm/m2 seem to be at a higher risk of death during follow-up after undergoing TAVR. In females, no such correlation was observed.

Cardiac MRI after Sudden Cardiac Arrest: A Systematic Review.

Purpose To perform a systematic review to assess the diagnostic and prognostic value of cardiac MRI after sudden cardiac arrest (SCA). Materials and Methods PubMed and Cochrane Library databases were systematically searched for studies investigating cardiac MRI after SCA in adult patients (≥18 years of age). The time frame of the encompassed studies spans from January 2012 to January 2023. The study protocol was preregistered in OSF Registries (www.osf.io/nxaev), and the systematic review was performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of the included studies was evaluated using the Newcastle-Ottawa quality assessment scale. Results Fourteen studies involving 1367 individuals, 1257 (91.9%) of whom underwent cardiac MRI, were included. Inconsistent findings were reported on the diagnostic value of cardiac MRI-specific findings. The included studies demonstrated the following main findings: (a) cardiac MRI led to a new or alternative diagnosis in patients with SCA; (b) cardiac MRI identified pathologic or arrhythmogenic substrates; (c) cardiac MRI helped detect myocardial edema (potentially reversible); (d) cardiac MRI provided evidence for the occurrence of adverse events; and (e) functional markers or ventricular dimensions were considered prognostically relevant in a few studies. Relevant challenges in this systematic review were the lack of comparators and reference standards relative to cardiac MRI as the index test and patient selection bias. Conclusion Cardiac MRI following SCA can contribute to the diagnostic process and offer supplementary information essential for treatment planning. Limitations of the review include studies with insufficient comparators and potential bias in patient selection. Systematic review registration link: osf.io/nxaev Keywords: Cardiac MRI, Cardiovascular Disease, Cardiomyopathy, Ischemia, Myocardial Edema, Sudden Cardiac Arrest © RSNA, 2024.

The impact of concomitant chronic total occlusion on clinical outcomes in patients undergoing transcatheter aortic valve replacement: a large single-center analysis.

Background: Coronary artery disease (CAD) is a common finding in patients with severe aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). However, the impact on prognosis of chronic total occlusions (CTOs), a drastic expression of CAD, remains unclear. Methods and results: We retrospectively reviewed 1,487 consecutive TAVR cases performed at a single tertiary care medical center. Pre-TAVR angiograms were analyzed for the presence of a CTO. At the time of TAVR, 11.2% (n = 167) patients had a CTO. There was no significant association between the presence of a CTO and in-hospital or 30-day mortality. There was also no difference in long-term survival. LV ejection fraction and mean aortic gradients were lower in the CTO group. Conclusions: Our analysis suggests that concomitant CTO lesions in patients undergoing TAVR differ in their risk profile and clinical findings to patients without CTO. CTO lesion per se were not associated with increased mortality, nevertheless CTOs which supply non-viable myocardium in TAVR population were associated with increased risk of death. Additional research is needed to evaluate the prognostic significance of CTO lesions in TAVR patients.

Elevated systolic pulmonary artery pressure is a substantial predictor of increased mortality after transcatheter aortic valve replacement in males, not in females.

BACKGROUND: While pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) is associated with increased mortality after transcatheter aortic valve replacement (TAVR), there is limited data on gender differences in the effects on long-term survival. OBJECTIVE: The aim of this retrospective, multicenter study was to investigate the prognostic impact of pre-interventional PH on survival of TAVR patients with respect to gender. METHODS: 303 patients undergoing TAVR underwent echocardiography to detect PH prior to TAVR via measurement of systolic pulmonary artery pressure (sPAP). Different cut-off values were set for the presence of PH. The primary endpoint was all-cause mortality at 1, 3 and 5 years. RESULTS: Kaplan-Meier analysis by gender showed that only males exhibited significant increased mortality at elevated sPAP values during the entire follow-up period of 5 years (sPAP ≥ 40 mmHg: p ≤ 0.001 and sPAP ≥ 50 mmHg: p ≤ 0.001 in 1- to 5-year survival), whereas high sPAP values had no effect on survival in females. In Cox regression analysis based on the selected sPAP thresholds, male gender was an independent risk factor for long-term mortality after TAVR in all time courses. CONCLUSION: Male gender was an isolated risk factor for premature death after TAVR in patients with echocardiographic evidence of PH and severe AS. This could mean that, the indication for TAVR should be discussed more critically in men with severe AS and an elevated sPAP, while in females, PH should not be an exclusion criterion for TAVR.

Hypertrophic cardiomyopathy is characterized by alterations of the mitochondrial calcium uniporter complex proteins: insights from patients with aortic valve stenosis versus hypertrophic obstructive cardiomyopathy.

Introduction: Hypertrophies of the cardiac septum are caused either by aortic valve stenosis (AVS) or by congenital hypertrophic obstructive cardiomyopathy (HOCM). As they induce cardiac remodeling, these cardiac pathologies may promote an arrhythmogenic substrate with associated malignant ventricular arrhythmias and may lead to heart failure. While altered calcium (Ca2+) handling seems to be a key player in the pathogenesis, the role of mitochondrial calcium handling was not investigated in these patients to date. Methods: To investigate this issue, cardiac septal samples were collected from patients undergoing myectomy during cardiac surgery for excessive septal hypertrophy and/or aortic valve replacement, caused by AVS and HOCM. Septal specimens were matched with cardiac tissue obtained from post-mortem controls without cardiac diseases (Ctrl). Results and discussion: Patient characteristics and most of the echocardiographic parameters did not differ between AVS and HOCM. Most notably, the interventricular septum thickness, diastolic (IVSd), was the greatest in HOCM patients. Histological and molecular analyses showed a trend towards higher fibrotic burden in both pathologies, when compared to Ctrl. Most notably, the mitochondrial Ca2+ uniporter (MCU) complex associated proteins were altered in both pathologies of left ventricular hypertrophy (LVH). On the one hand, the expression pattern of the MCU complex subunits MCU and MICU1 were shown to be markedly increased, especially in AVS. On the other hand, PRMT-1, UCP-2, and UCP-3 declined with hypertrophy. These conditions were associated with an increase in the expression patterns of the Ca2+ uptaking ion channel SERCA2a in AVS (p = 0.0013), though not in HOCM, compared to healthy tissue. Our data obtained from human specimen from AVS or HOCM indicates major alterations in the expression of the mitochondrial calcium uniporter complex and associated proteins. Thus, in cardiac septal hypertrophies, besides modifications of cytosolic calcium handling, impaired mitochondrial uptake might be a key player in disease progression.

Large Bouncing Mass in the Right Atrium: Metastasis of Malignant Melanoma.

This paper presents a rare case of malignant melanoma metastasizing to the heart, highlighting the diagnostic journey, therapeutic considerations, and clinical implications. Enhanced awareness of atypical metastases aids early recognition and treatment strategies for improved patient care. Comprehensive understanding of cardiac involvement in melanoma contributes to better outcomes and clinical decision making. (Level of Difficulty: Beginner.).

MicroRNA-30d-5p-A Potential New Therapeutic Target for Prevention of Ischemic Cardiomyopathy after Myocardial Infarction.

(1) Background and Objective: MicroRNAs (miRs) are biomarkers for assessing the extent of cardiac remodeling after myocardial infarction (MI) and important predictors of clinical outcome in heart failure. Overexpression of miR-30d-5p appears to have a cardioprotective effect. The aim of the present study was to demonstrate whether miR-30d-5p could be used as a potential therapeutic target to improve post-MI adverse remodeling. (2) Methods and Results: MiR profiling was performed by next-generation sequencing to assess different expression patterns in ischemic vs. healthy myocardium in a rat model of MI. MiR-30d-5p was significantly downregulated (p < 0.001) in ischemic myocardium and was selected as a promising target. A mimic of miR-30d-5p was administered in the treatment group, whereas the control group received non-functional, scrambled siRNA. To measure the effect of miR-30d-5p on infarct area size of the left ventricle, the rats were randomized and treated with miR-30d-5p or scrambled siRNA. Histological planimetry was performed 72 h and 6 weeks after induction of MI. Infarct area was significantly reduced at 72 h and at 6 weeks by using miR-30d-5p (72 h: 22.89 ± 7.66% vs. 35.96 ± 9.27%, p = 0.0136; 6 weeks: 6.93 ± 4.58% vs. 12.48 ± 7.09%, p = 0.0172). To gain insight into infarct healing, scratch assays were used to obtain information on cell migration in human umbilical vein endothelial cells (HUVECs). Gap closure was significantly faster in the mimic-treated cells 20 h post-scratching (12.4% more than the scrambled control after 20 h; p = 0.013). To analyze the anti-apoptotic quality of miR-30d-5p, the ratio between phosphorylated p53 and total p53 was evaluated in human cardiomyocytes using ELISA. Under the influence of the miR-30d-5p mimic, cardiomyocytes demonstrated a decreased pp53/total p53 ratio (0.66 ± 0.08 vs. 0.81 ± 0.17), showing a distinct tendency (p = 0.055) to decrease the apoptosis rate compared to the control group. (3) Conclusion: Using a mimic of miR-30d-5p underlines the cardioprotective effect of miR-30d-5p in MI and could reduce the risk for development of ischemic cardiomyopathy.

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.

Diverging Concentrations of Soluble Suppression of Tumorigenicity (sST2) Analyzed by two Different Assays - a Limitation for its use in Clinical Practice?

BACKGROUND: Soluble suppression of tumorigenicity (sST2) constitutes a novel biomarker with diagnostic and prognostic implications in several diseases. However, recent evidence suggests that different enzyme-linked immunosorbent assay (ELISA) kits could result in diverging serum concentrations measured. METHODS: Serum concentrations of sST2 were measured in blood of 215 patients with aortic valve stenosis using two commercially available ELISA-assays (Presage® ST2 assay and R&D). Passing and Bablok regression analysis, Bland-Altman plot, and correlation analysis were conducted. RESULTS: Values obtained by Presage® were 1.9-fold higher than concentrations measured by R&D, with a mean bias of 14,489 pg/mL between both assays. The most extreme deviations were observed in values below the median of concentrations measured by the R&D assay (21.4%, p < 0.0001). CONCLUSIONS: Our findings suggest a constant difference and a proportional bias between both investigated assays could be of special importance in circumstances where cutoffs with prognostic relevance have been calculated previously. In order to interpret sST2 concentrations correctly, the clinician should be aware of these deviations between different ELISA kits.

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.

Prophylactic rivaroxaban in the early post-discharge period reduces the rates of hospitalization for atrial fibrillation and incidence of sudden cardiac death during long-term follow-up in hospitalized COVID-19 survivors.

Introduction: While acute Coronavirus disease 2019 (COVID-19) affects the cardiovascular (CV) system according to recent data, an increased CV risk has been reported also during long-term follow-up (FU). In addition to other CV pathologies in COVID-19 survivors, an enhanced risk for arrhythmic events and sudden cardiac death (SCD) has been observed. While recommendations on post-discharge thromboprophylaxis are conflicting in this population, prophylactic short-term rivaroxaban therapy after hospital discharge showed promising results. However, the impact of this regimen on the incidence of cardiac arrhythmias has not been evaluated to date. Methods: To investigate the efficacy of this therapy, we conducted a single center, retrospective analysis of 1804 consecutive, hospitalized COVID-19 survivors between April and December 2020. Patients received either a 30-day post-discharge thromboprophylaxis treatment regimen using rivaroxaban 10 mg every day (QD) (Rivaroxaban group (Riva); n = 996) or no thromboprophylaxis (Control group (Ctrl); n = 808). Hospitalization for new atrial fibrillation (AF), new higher-degree Atrioventricular-block (AVB) as well as incidence of SCD were investigated in 12-month FU [FU: 347 (310/449) days]. Results: No differences in baseline characteristics (Ctrl vs Riva: age: 59.0 (48.9/66.8) vs 57 (46.5/64.9) years, p = n.s.; male: 41.5% vs 43.7%, p = n.s.) and in the history of relevant CV-disease were observed between the two groups. While hospitalizations for AVB were not reported in either group, relevant rates of hospitalizations for new AF (0.99%, n = 8/808) as well as a high rate of SCD events (2.35%, n = 19/808) were seen in the Ctrl. These cardiac events were attenuated by early post-discharge prophylactic rivaroxaban therapy (AF: n = 2/996, 0.20%, p = 0.026 and SCD: n = 3/996, 0.30%, p < 0.001) which was also observed after applying a logistic regression model for propensity score matching (AF: χ 2-statistics = 6.45, p = 0.013 and SCD: χ 2-statistics = 9.33, p = 0.002). Of note, no major bleeding complications were observed in either group. Conclusion: Atrial arrhythmic and SCD events are present during the first 12 months after hospitalization for COVID-19. Extended prophylactic Rivaroxaban therapy after hospital discharge could reduce new onset of AF and SCD in hospitalized COVID-19 survivors.

Biomarkers of Atrial Fibrillation Recurrence in Patients with Paroxysmal or Persistent Atrial Fibrillation Following External Direct Current Electrical Cardioversion.

Atrial fibrillation (AF) is associated with atrial remodeling, cardiac dysfunction, and poor clinical outcomes. External direct current electrical cardioversion is a well-developed urgent treatment strategy for patients presenting with recent-onset AF. However, there is a lack of accurate predictive serum biomarkers to identify the risks of AF relapse after electrical cardioversion. We reviewed the currently available data and interpreted the findings of several studies revealing biomarkers for crucial elements in the pathogenesis of AF and affecting cardiac remodeling, fibrosis, inflammation, endothelial dysfunction, oxidative stress, adipose tissue dysfunction, myopathy, and mitochondrial dysfunction. Although there is ample strong evidence that elevated levels of numerous biomarkers (such as natriuretic peptides, C-reactive protein, galectin-3, soluble suppressor tumorigenicity-2, fibroblast growth factor-23, turn-over collagen biomarkers, growth differential factor-15) are associated with AF occurrence, the data obtained in clinical studies seem to be controversial in terms of their predictive ability for post-cardioversion outcomes. Novel circulating biomarkers are needed to elucidate the modality of this approach compared with conventional predictive tools. Conclusions: Biomarker-based strategies for predicting events after AF treatment require extensive investigation in the future, especially in the presence of different gender and variable comorbidity profiles. Perhaps, a multiple biomarker approach exerts more utilization for patients with different forms of AF than single biomarker use.

Effects of Angiotensin Receptor-Neprilysin Inhibitors (ARNIs) on the Glucose and Fat Metabolism Biomarkers Leptin and Fructosamine.

(1) Background: Heart failure with reduced ejection fraction (HFrEF) remains a major health burden. Angiotensin-Receptor-Neprilysin-Inhibitors (ARNIs) are an established HFrEF therapy which increases natriuretic peptide levels by inhibiting neprilysin. Leptin is a lipid metabolism parameter, which is also involved in glucose metabolism and is suggested to correlate with HF burden. While the hormone also seems to interact with neprilysin, potential associations with ARNI therapy have not been investigated yet. (2) Methods: To study this issue, we measured levels of leptin and fructosamine in consecutive 72 HFrEF patients before initiation of ARNI therapy and 3-6 months after initiation of therapy in two European centers. Biomarker levels were correlated with clinical parameters including ejection fraction, LVEF, and NYHA class. (3) Results: During a follow-up of up to 6 months, clinical parameters improved significantly (LVEF: 30.2 ± 7.8% to 37.6 ± 10.0%, (p < 0.001) and a significant improvement of the mean NYHA class with initial 32 patients in NYHA III or IV and 8 patients in NYHA class III/IV during the follow up (p < 0.001). The initial NT-proBNP levels of 2251.5 ± 2566.8 pg/mL significantly improved to 1416.7 ± 2145 pg/mL, p = 0.008) during follow up. ARNI therapy was also associated with an increase in leptin levels (17.5 ± 23.4 µg/L to 22.9 ± 29.3, p < 0.001) and furthermore, affected glucose metabolism indicated by elevation of fructosamine values (333.9 ± 156.8 µmol/L to 454.8 ± 197.8 µmol/L, p = 0.013). (4) Conclusion: while in the early phase of therapy, ARNI promotes clinical improvement of HFrEF, and it also seems to affect fat and glucose parameters, indicating significant metabolic implications of this therapy regime.

Impact of cavotricuspid isthmus ablation for typical atrial flutter and heart failure in the elderly-results of a retrospective multi-center study.

Introduction: While in the CASTLE-AF trial, in patients with atrial fibrillation and heart failure with reduced ejection fraction, interventional therapy using pulmonary vein isolation was associated with outcome improvement, data on cavotricuspid isthmus ablation (CTIA) in atrial flutter (AFL) in the elderly is rare. Methods: We included 96 patients between 60 and 85 years with typical AFL and heart failure with reduced or mildly reduced ejection fraction (HFrEF/HFmrEF) treated in two medical centers. 48 patients underwent an electrophysiological study with CTIA, whereas 48 patients received rate or rhythm control and guideline-compliant heart failure therapy. Patients were followed up for 2 years, with emphasis on left ventricular ejection fraction (LVEF) over time. Primary endpoints were cardiovascular mortality and hospitalization for cardiac causes. Results: Patients with CTIA showed a significant increase in LVEF after 1 (p < 0.001) and 2 years (p < 0.001) in contrast to baseline LVEF. Improvement of LVEF in the CTIA group was associated with significantly lower 2-year mortality (p = 0.003). In the multivariate regression analysis, CTIA remained the relevant factor associated with LVEF improvement (HR: 2.845 CI:95% 1.044-7.755; p = 0.041). Elderly patients (≥ 70 years) further benefited from CTIA, since they showed a significantly reduced rehospitalization (p = 0.042) and mortality rate after 2 years (p = 0.013). Conclusions: CTIA in patients with typical AFL and HFrEF/HFmrEF was associated with significant improvement of LVEF and reduced mortality rates after 2 years. Patient age should not be a primary exclusion criterion for CTIA, since patients ≥70 years also seem to benefit from intervention in terms of mortality and hospitalization.

CT measured pulmonary artery to ascending aorta ratio stratified by echocardiographically obtained systolic pulmonary artery pressure values for noninvasive detection of pulmonary hypertension in patients with severe aortic valve stenosis.

BACKGROUND: Transthoracic echocardiography (TTE) offers a measurement method for the determination of pulmonary hypertension (PH) in patients with severe aortic valve stenosis (AS) with determination of maximal tricuspid regurgitation velocity (TRVmax) and systolic pulmonary artery pressure (sPAP). Radiological parameters for noninvasive detection of PH, most importantly computed tomography (CT) based PA/AA-ratio = ratio of pulmonary artery diameter (PA) and ascending aorta diameter (AA), are also included in the latest ESC guidelines. The aim of the present study was to define cut-off values for PA/AA-ratio taking also into account cardiovascular biomarkers to determine criteria for noninvasive diagnosis of PH. METHODS: 194 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR) underwent pre-procedural TTE and CT with measurement of PA/AA-ratio. Additionally, common cardiovascular biomarkers were determined. RESULTS: TAVR patients with an sPAP ≥ 40 mmHg or a TRVmax ≥ 2.9 m/s had a PA/AA-ratio ≥ 0.80 in an AUROC analysis. The cut-off value of ≥ 0.80 resulted in a significantly higher mortality rate (log-rank test: p = 0.034) in these patients in a Kaplan-Meier analysis regarding 1-year survival after TAVR. Significant differences in biomarker expression between patients with a PA/AA-ratio ≥ 0.80 or < 0.80 occurred for BNP (p = 0.001), cTnI (p = 0.032), GDF-15 (p = 0.002) and H-FABP (p = 0.015). CONCLUSION: PA/AA-ratio ≥ 0.80 is a promising radiological parameter that can provide information about mortality in patients with severe AS undergoing TAVR; combined with biomarkers it may contribute to noninvasive detection of PH in patients with severe AS.

The Presence of Ascending Aortic Dilatation in Patients Undergoing Transcatheter Aortic Valve Replacement Is Negatively Correlated with the Presence of Diabetes Mellitus and Does Not Impair Post-Procedural Outcomes.

Both relevant aortic valve stenosis (AS) and aortic valve insufficiency significantly contribute to structural changes in the ascending aorta (AA) and thus to its dilatation. In patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), survival data regarding aortic changes and laboratory biomarker analyses are scarce. METHODS: A total of 179 patients with severe AS and an available computed tomography were included in this retrospective study. AA was measured, and dilatation was defined as a diameter ≥ 40 mm. Thirty-two patients had dilatation of the AA. A further 32 patients from the present population with a normal AA were matched to the aortic dilatation group with respect to gender, age, body mass index and body surface area, and the resulting study groups were compared with each other. In addition to echocardiographic and clinical characteristics, the expression of cardiovascular biomarkers such as brain natriuretic peptide (BNP), soluble suppression of tumorigenicity-2 (sST2), growth/differentiation of factor-15 (GDF-15), heart-type fatty-acid binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2) and soluble urokinase-type plasminogen activator receptor (suPAR) was analyzed. Kaplan-Meier curves for short- and long-term survival were obtained, and Pearson's and Spearman's correlations were calculated to identify the predictors between the diameter of the AA and clinical parameters. RESULTS: A total of 19% of the total cohort had dilatation of the AA. The study group with an AA diameter ≥ 40 mm showed a significantly low comorbidity with respect to diabetes mellitus in contrast to the comparison cohort with an AA diameter < 40 mm (p = 0.010). This result continued in the correlation analyses performed, as the presence of diabetes mellitus correlated negatively not only with the diameter of the AA (r = -0.404; p = 0.001) but also with the presence of aortic dilatation (r = -0.320; p = 0.010). In addition, the presence of AA dilatation after TAVR was shown to have no differences in terms of patient survival at 1, 3 and 5 years. There were no relevant differences in the cardiovascular biomarkers studied between the patients with dilated and normal AAs. CONCLUSION: The presence of AA dilatation before successful TAVR was not associated with a survival disadvantage at the respective follow-up intervals of 1, 3 and 5 years. Diabetes mellitus in general seemed to have a protective effect against the development of AA dilatation or aneurysm in patients with severe AS.

A Story of PA/BSA and Biomarkers to Diagnose Pulmonary Hypertension in Patients with Severe Aortic Valve Stenosis-The Rise of IGF-BP2 and GDF-15.

(1) Background: Currently, echocardiography is the primary non-invasive diagnostic method used to screen patients with severe aortic valve stenosis (AS) for pulmonary hypertension (PH) by estimating systolic pulmonary artery pressure (sPAP). Other radiological methods have been a focus of research in the past couple of years, as it was shown that by determining the pulmonary artery (PA) diameter, prognostic statements concerning overall mortality could be made in these patients. This study compared established and novel cardiovascular biomarkers with the PA/BSA value to detect PH in patients with severe AS. (2) Methods: The study cohort comprised 188 patients with severe AS undergoing transcatheter aortic valve replacement (TAVR), who were then divided into two groups based on PA/BSA values obtained through CT-angiography. The presence of PH was defined as a PA/BSA ≥ 16.6 mm/m2 (n = 81), and absence as a PA/BSA < 16.6 mm/m2 (n = 107). Blood samples were taken before TAVR to assess cardiovascular biomarkers used in this study, namely brain natriuretic peptide (BNP), cardiac troponin I (cTnI), high-sensitive troponin (hsTN), soluble suppression of tumorigenesis-2 (sST2), growth/differentiation factor 15 (GDF-15), heart-type fatty acid-binding protein (H-FABP), insulin-like growth factor binding protein 2 (IGF-BP2), and soluble urokinase-type plasminogen activator receptor (suPAR). (3) Results: Patients with a PA/BSA ≥ 16.6 mm/m2 showed significantly higher levels of BNP (p = <0.001), GDF-15 (p = 0.040), and H-FABP (p = 0.007). The other investigated cardiovascular biomarkers did not significantly differ between the two groups. To predict a PA/BSA ≥ 16.6 mm/m2, cut-off values for the biomarkers were calculated. Here, GDF-15 (p = 0.029; cut-off 1172.0 pg/mL) and BNP (p < 0.001; cut-off 2194.0 pg/mL) showed significant results. Consequently, analyses of combined biomarkers were performed, which yielded IGF-BP2 + BNP (AUC = 0.721; 95%CI = 0.585−0.857; p = 0.004) as the best result of the two-way analyses and GDF-15 + IGF-BP2 + BNP (AUC = 0.727; 95%CI = 0.590−0.864; p = 0.004) as the best result of the three-way analyses. No significant difference regarding the 1-year survival between patients with PA/BSA < 16.6 mm/m2 and patients with PA/BSA ≥ 16.6 mm/m2 was found (log-rank test: p = 0.452). (4) Conclusions: Although PA/BSA aims to reduce the bias of the PA value caused by different body compositions and sizes, it is still a controversial parameter for diagnosing PH. Combining the parameter with different cardiovascular biomarkers did not lead to a significant increase in the diagnostic precision for detecting PH in patients with severe AS.