Insulin resistance and central obesity determine hepatic steatosis and explain cardiovascular risk in steatotic liver disease.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed to replace non-alcoholic fatty liver disease and focus on patients with progressive disease due to the presence of metabolic dysfunction. However, it is unclear whether the new definition actually identifies patients with hepatic steatosis at increased cardiovascular risk. Methods: A total of 4,286 asymptomatic subjects from the SAKKOPI study aged 45-80 years undergoing screening colonoscopy were analyzed. Steatosis was diagnosed by abdominal ultrasound. MASLD was diagnosed according to the recent expert consensus. Insulin resistance was assessed by homeostasis model assessment-insulin resistance score (HOMA-IR) (cutoff: ≥2.5), subclinical inflammation was estimated by ferritin/CRP/uric acid, and cardiovascular risk was assessed using SCORE2/ASCVD. Results: Mean age was 59.4 ± 8.5 years, 51.6% were male; mean BMI was 27.0 ± 4.5 kg/m², 9.2% had type 2 diabetes mellitus. In total, 1,903 (44.4%) were diagnosed with hepatic steatosis and were characterized by more severe metabolic dysfunction including insulin resistance (47.1% vs. 12.2%, p < 0.001) and central obesity (waist circumference ≥102/88 cm, 71.8% vs. 37.1%, p < 0.001). This translated into higher (subclinical) inflammation (ferritin 153 vs. 95 mg/dL, p < 0.001, uric acid 6.3 mg/dL vs. 5.2 mg/dL, p < 0.001) and 10-year cardiovascular risk (SCORE2 7.8 points vs. 5.1 points, p < 0.001, ASCVD 17.9 points vs. 10.8 points, p < 0.001). 99.0% of subjects with steatosis met the MASLD definition, 95.4% met the MAFLD definition, and 53.6% met the definition of metabolic syndrome, while 95.4% of subjects without steatosis also met the MASLD criteria for metabolic dysfunction compared to 69.0% and 17.4% who met the MAFLD and metabolic syndrome criteria, respectively. Forward stepwise regression indicated that waist circumference, HOMA-IR, and triglycerides were most relevant in explaining the presence of hepatic steatosis across all subgroups of increasing metabolic dysfunction. At the same time, hepatic steatosis was not associated with cardiovascular risk in the overall cohort (SCORE2: B = 0.060, 95% CI: -0.193-0.314, and p = 0.642) and in patients with metabolic dysfunction after adjusting for age, sex, and these three metabolic dysfunction components. Conclusion: Although hepatic steatosis is associated with increased central obesity and insulin resistance, metabolic dysfunction per se rather than hepatic steatosis explains cardiovascular risk in these patients.

Investigation of hs-TnI and sST-2 as Potential Predictors of Long-Term Cardiovascular Risk in Patients with Survived Hospitalization for COVID-19 Pneumonia.

Introduction: COVID-19 survivors reveal an increased long-term risk for cardiovascular disease. Biomarkers like troponins and sST-2 improve stratification of cardiovascular risk. Nevertheless, their prognostic value for identifying long-term cardiovascular risk after having survived COVID-19 has yet to be evaluated. Methods: In this single-center study, admission serum biomarkers of sST-2 and hs-TnI in a single cohort of 251 hospitalized COVID-19 survivors were evaluated. Concentrations were correlated with major cardiovascular events (MACE) defined as cardiovascular death and/or need for cardiovascular hospitalization during follow-up after hospital discharge [FU: 415 days (403; 422)]. Results: MACE was a frequent finding during FU with an incidence of 8.4% (cardiovascular death: 2.8% and/or need for cardiovascular hospitalization: 7.2%). Both biomarkers were reliable indicators of MACE (hs-TnI: sensitivity = 66.7% & specificity = 65.7%; sST-2: sensitivity = 33.3% & specificity = 97.4%). This was confirmed in a multivariate proportional-hazards analysis: besides age (HR = 1.047, 95% CI = 1.012−1.084, p = 0.009), hs-TnI (HR = 4.940, 95% CI = 1.904−12.816, p = 0.001) and sST-2 (HR = 10.901, 95% CI = 4.509−29.271, p < 0.001) were strong predictors of MACE. The predictive value of the model was further improved by combining both biomarkers with the factor age (concordance index hs-TnI + sST2 + age = 0.812). Conclusion: During long-term FU, hospitalized COVID-19 survivors, hs-TnI and sST-2 at admission, were strong predictors of MACE, indicating both proteins to be involved in post-acute sequelae of COVID-19.

Case report: Short-long-short mechanism triggering sustained ventricular tachycardia in a patient with a single-chamber ICD but inhibiting antitachycardia therapy.

Introduction: Short-long-short (SLS) sequences are an important cause of ICD pro-arrhythmia and can initiate both polymorphic and monomorphic ventricular tachycardias (VT). Depending on the programming of a single-chamber ICD, the interplay between SLS sequences and combined VT detection criteria can be responsible for withholding adequate anti-tachycardia pacing (ATP) or shock therapy. Methods: A 78-year-old patient with ICD was admitted to our emergency department after external cardioversion of a long-lasting VT with hemodynamic compromise. The interrogation of the ICD revealed an SLS sequence initiating a monomorphic VT at a rate of 171 bpm (350 ms). The VT discrimination of the implanted single-chamber ICD was based on the onset and stability criteria as the patient had a history of paroxysmal atrial fibrillation. The ICD was programmed that both criteria had to be met for VT detection and initiation of anti-tachycardia therapy. Results: Due to the SLS sequence in combination with the programmed VT detection interval, the onset threshold was not fulfilled and inhibited adequate therapy. Some relatively slow VT beats following the SLS sequence resulted finally in a considerable delay in the declaration of the episode onset. As a first step, the threshold for VT detection was programmed to 150 instead of 160 bpm. To avoid SLS sequences and pause-dependent ventricular tachyarrhythmias, VVI backup stimulation was increased from 35 to 55 ppm. Besides, a device-specific algorithm called rate smoothing was activated as a potential preventive feature. On the 3-month follow-up, all sustained VT episodes were detected adequately by the reprogrammed device, resulting in appropriate anti-tachycardia pacing. After further refinement and less aggressive programming of rate smoothing, the patient remained free of symptoms and arrhythmias over a follow-up of more than 2.5 years, particularly since progression to permanent atrial fibrillation and pacing at a lower rate of 60 ppm. Conclusions: SLS sequences may initiate or trigger VT episodes. Misclassification of the true onset may occur in some ICD devices due to specific programming of VT detection criteria. If both criteria "Onset and Stability" have to be fulfilled, ICD therapy is not delivered despite ongoing VT. Anti-bradycardia backup pacing at a very low stimulation rate may facilitate SLS sequences in patients with ICD resembling a potential pro-arrhythmic mechanism. In case of gradual VT onset with some intervals slower than the programmed VT threshold, the detection rate has to be adjusted down to guarantee appropriate identification of the onset.