Markus Wallner

Background: Although beneficial effects of red wine and its polyphenols have been described, data on direct effects on pulmonary arteries and human myocardium are sparse, and claims remain controversial given well-known alcohol-related harms. Aims: This study investigated acute and subacute effects of red wine, dealcoholized red wine and key polyphenols (trans/cis-resveratrol, caffeic acid, gallic acid) on human atrial and ventricular myocardium and pulmonary arteries. Methods and Results: In human atrial trabeculae and failing left ventricular slices from heart transplant recipients (n = 6), polyphenols increased developed force significantly (+39% caffeic acid, +27% gallic acid, +17% trans-resveratrol, +10% cis-resveratrol; control −34%, p < 0.05) and red wine (10−4: +18%) compared with control (−23%, p < 0.0001), without affecting diastolic properties or inducing arrhythmias. In failing human left ventricular myocardium, twitch amplitude increased over 7 days with alcoholic and dealcoholized red wine (p = 0.0177) compared with control, while preserving the negative force–frequency relationship and post-rest potentiation. In preconstricted human pulmonary arteries, red wines induced a rapid, sustained 80% relaxation independent of ethanol content. L-NAME reduced human pulmonary artery relaxation from 59% to 28% (p < 0.05), confirming partial endothelial nitric-oxide mediation. Conclusion: Red wine and its bioactive compounds exert robust dual inotropic and pulmonary vasodilatory actions independent of alcohol. Dealcoholized red wine as an adjunctive strategy may represent a promising avenue toward integrated cardiopulmonary therapy in heart failure and precapillary pulmonary hypertension. A clinical trial (DARE-WINE-PH, DRKS00035605) is underway to validate acute haemodynamic effects in patients with precapillary pulmonary hypertension.

Giant cell myocarditis (GCM) is a rare but devastating inflammatory cardiac disease characterized by rapid hemodynamic deterioration, malignant arrhythmias, and high rates of death or heart transplantation. Without immunosuppressive treatment, median transplant-free survival is approximately three months. Current evidence identifies GCM as a predominantly T cell–mediated autoimmune disorder driven by a breakdown of immune tolerance, with contributions from macrophage-derived multinucleated giant cells and neutrophil extracellular trap formation. Viral infections and environmental factors have been implicated as potential triggers. GCM typically affects middle-aged adults, with concomitant non-cardiac autoimmune diseases present in approximately 20% of cases. Early diagnosis remains challenging, as clinical presentation and imaging findings are nonspecific and overlap considerably with cardiac sarcoidosis. Endomyocardial biopsy continues to represent the diagnostic gold standard, with a sensitivity of 85%, while cardiac biomarkers including cardiac troponins and NT-proBNP provide important prognostic information. Cardiac magnetic resonance imaging and FDG-PET contribute to the diagnostic workup but cannot reliably differentiate GCM from cardiac sarcoidosis. Management requires prompt initiation of combination immunosuppressive therapy—typically corticosteroids combined with T cell–targeted agents such as cyclosporine and azathioprine or tacrolimus and mycophenolate mofetil, which has substantially improved survival in contemporary registries. Mechanical circulatory support and heart transplantation are frequently required for refractory cases. Given the high arrhythmic burden, systematic evaluation for implantable cardioverter-defibrillator placement is recommended. This review provides a comprehensive overview of the pathogenesis, diagnosis, and current management of GCM and highlights priorities for future research, including noninvasive diagnostic tools and standardized treatment protocols.

Background: Sodium glucose-linked transport 2 inhibitors (SGLT2-Is) are well known to exert beneficial effects in chronic heart failure (CHF) independent of left ventricular ejection fraction (LVEF). As inflammation plays a key role in cardiac diseases, data on the association of inflammatory biomarkers and ventricular arrhythmic (VA) burden in SGLT2-I-treated patients is lacking. Methods: This pre-defined subanalysis investigated changes in pre-specified inflammatory biomarkers from baseline to week 52 in response to 5 mg Ertugliflozin compared to placebo and their associations to the incidence of VA burden. Results: A total of 36 patients (18 versus 18) with available biobank samples were included in the analysis. At week 52, leukocyte and neutrophil counts, as well as high-sensitive C-reactive protein (hsCRP) and interleukin-6 (IL-6), were numerically higher in the Ertugliflozin group. In contrast, neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were lower in the Ertugliflozin group, although these differences did not reach statistical significance. Notably, lymphocyte counts were significantly higher in Ertugliflozin showing a mean difference of 19.0 ± 10.78% (p = 0.028). Further, a significantly higher incidence of VA burden was observed among Ertugliflozin-treated patients with elevated hsCRP levels (incidence rate ratio [IRR] 3.58; 95% Confidence interval [CI], 1.12–11.40, p = 0.031). Conclusions: In patients with CHF, Ertugliflozin treatment was associated with a higher incidence of VA burden in those with elevated hsCRP levels. This may suggest a potential higher risk for VA in SGLT2-I-treated patients in the setting of heightened inflammatory activity. However, this finding is based on a single interaction analysis in a small sample size, and the results should therefore be considered exploratory and hypothesis-generating, and must be interpreted cautiously.

Background/Objectives: Ertugliflozin showed a beneficial effect to reduce arrhythmic burden in heart failure patients with an ejection fraction less than 50% with an implantable cardioverter-defibrillator (ICD) with or without cardiac resynchronization therapy device (CRT-D) in the ERASe trial. The aim of the post hoc sub-analysis of the ERASe trial was to compare the effect of ertugliflozin versus placebo on structural and functional parameters assessed by echocardiography. Methods: In this sub-analysis of the ERASe trial, 40 patients (87% of the overall ERASe trial cohort) with stored echocardiography loops and adequate image quality were included. A post hoc analysis including structural and functional echocardiography parameters was performed by a trained investigator blinded to the treatment group. Results: After 52 weeks of treatment, there were no between-group differences in left and right ventricular dimensions (left ventricular end-diastolic and -systolic volumes, right ventricular diameter) and function (left ventricular ejection fraction [LVEF], tricuspid annular plane systolic excursion), after adjustment for baseline values. Lower LVEF at baseline was associated with a higher number of ventricular arrhythmias in both treatment groups. Conclusions: In this sub-analysis of the ERASe trial, treatment with ertugliflozin did not improve structural and functional parameters assessed by echocardiography after 52 weeks of treatment compared to placebo despite the significant reduction in arrhythmic burden.

Background: Triazoles (eg, isavuconazole, posaconazole, voriconazole) are the first-line treatment for invasive pulmonary aspergillosis (IPA), but their use can be limited by drug interactions, hepatotoxicity, and emerging azole resistance. Recent guidelines recommend echinocandins as a safe and well-tolerated first-line alternative. Methods: In this multicenter observational study across 9 treatment centers, we included all consecutive patients with IPA from 1 January 2014 to 1 June 2024. We compared 30-day overall survival (OS) as the primary outcome and 90-day OS as the secondary outcome between patients receiving triazoles versus echinocandins as first-line therapy. Propensity score adjustment was applied to address baseline characteristic imbalances. Results: We included 177 patients, of whom 153 (86%) received triazoles as first-line therapy (69 voriconazole, 54 isavuconazole, 30 posaconazole). Before propensity score adjustment, patients treated with echinocandins were significantly sicker, with higher rates of intensive care treatment (95% vs 75%, P = .002). In both crude and propensity score–adjusted analyses, 30-day mortality was significantly higher in the echinocandin group compared to the triazole group (63% [95% CI 55–70] vs 30% [95% CI 13–50], P < .001). Even switching from echinocandins after initial treatment failure to salvage therapy did not mitigate the negative impact on OS. Switching from triazoles (28/153 cases) was mainly due to tolerability concerns, while echinocandins (12 cases) were switched for treatment failure. Conclusions: Using echinocandins as alternative first-line treatment for IPA may result in poorer survival outcomes and should be approached with caution until further trials confirm our findings.

Background/Objectives: The impact of cold temperature on heart failure (HF) decompensations in continental climate zones is unclear. We aimed to evaluate the association between daily temperature and the subsequent frequency of HF decompensations in an emergency department (ED) in Eastern Austria. Methods: A systematic retrospective medical chart review of all admissions to the ED of a tertiary care center within 12 months was conducted. Maximal daily temperature and further meteorological data were obtained from the National Institute for Meteorology and Geodynamics. Results: Among 32.028 ED admissions, there were 1.248 HF decompensations. Median maximal daily temperature ranged from 4.3 °C in January to 28.7 °C in August, and the frequency of decompensations ranged from 65 in August to 143 in January. Maximal daily temperature correlated negatively with the number of decompensations on the subsequent day (beta = −0.07 [95% confidence interval, −0.09 to −0.05], p < 0.001). The association remained significant in a multivariate linear regression model adjusted for other meteorological parameters (adjusted beta = −0.07 [−0.10 to −0.04], p < 0.001). Moreover, it was present across HF with preserved (n = 375; beta = −0.08 [−0.14 to −0.03], p = 0.004) and reduced (n = 331; beta = −0.08 [−0.13 to −0.02], p = 0.005) ejection fraction, but not with mildly reduced ejection fraction (n = 160; beta = −0.03 [−0.07 to 0.01], p = 0.200). Conclusions: In a European continental climate zone region, lower temperature was associated with a linear increase in subsequent HF decompensations. The sequelae of climate change on HF decompensations may burden healthcare systems in the future and should be systematically investigated in further studies.

Background: Patients with transthyretin amyloid cardiomyopathy (ATTR-CM) represent a high-risk heart failure population with continued unmet therapeutic needs. Sodium–glucose co-transporter 2 inhibitors (SGLT2i) improve cardiovascular outcomes in patients with heart failure across the whole spectrum of ejection fraction, and first evidence regarding their safety and effectiveness in patients with ATTR-CM is arising. This study investigates the association between SGLT2i therapy and clinical outcomes in these patients. Methods: This is an analysis of a prospective registry conducted at a referral centre for hypertrophic cardiomyopathies including 116 patients with confirmed ATTR-CM. Fifty-one patients (44%) were treated with SGLT2i while 65 patients (56%) remained SGLT2i-naïve. Results: During a median follow-up of 2.6 (1.7–3.7) years, 38 patients (33%) died, of whom 11 patients (9%) received SGLT2i treatment and 27 patients (23%) were treatment-naïve. SGLT2i therapy was significantly associated with lower mortality (HR 0.457, 95%CI 0.227–0.922, p = 0.029). This association persisted after adjusting for age and sex (HR 0.479, 95%CI 0.235–0.977, p = 0.043) and after additional adjustment for eGFR, NT-proBNP, LVEF, and concomitant therapy with tafamidis (HR 0.328, 95%CI 0.141–0.760, p = 0.009). However, when potential immortal time bias was considered, this association lost statistical significance (HR 1.075, 95%CI 0.524–2.206, p = 0.843). No significant associations between SGLT2i therapy and worsening heart-failure hospitalization or cardiovascular mortality were observed. Conclusions: In crude analysis, SGLT2i therapy associates with better survival in patients with ATTR-CM. However, after adjustment for immortal time, this association becomes statistically insignificant. Hence, to draw final conclusions on the effectiveness of SGLT2i therapy in these patients, a randomized controlled trial is warranted.

Background: In patients with stable chronic heart failure with a reduced ejection fraction (HFrEF), left ventricular ejection fraction (LVEF) provides limited prognostic value, especially in patients with moderately to severely reduced LVEF. Echocardiographic parameters of right ventricular function may be associated with adverse clinical events in these patients. Therefore, we analyzed 164 patients with HFrEF in a prospective single-center cohort study to evaluate whether the parameters of right ventricular function are associated with worsening heart failure (WHF) hospitalizations, cardiovascular and all-cause deaths and combined endpoints. Methods: Echocardiographic cine loops were analyzed using vendor-independent post-processing software. Multivariate Cox regression analyses were performed, which were then adjusted for clinical characteristics and left ventricular functional parameters. Results: In these models, higher tricuspid annular plane systolic excursion (TAPSE) was significantly associated with lower rates of WHF hospitalizations (HR 0.880, 95%CI 0.800–0.968, p = 0.008), a composite endpoint of WHF hospitalizations and cardiovascular death (HR 0.878, 95%CI 0.800–0.964, p = 0.006), and a composite endpoint of WHF hospitalization and all-cause death (HR 0.918, 95%CI 0.853–0.988, p = 0.023). These associations were more pronounced in patients with LVEF ≤ 35%. Conclusions: In conclusion, in patients with HFrEF, TAPSE is an independent prognosticator for adverse clinical outcomes, warranting further studies to elucidate whether incorporating TAPSE into established risk scores improves their diagnostic accuracy.

(1) Background: Mechanical circulatory support (MCS) in myocardial infarction-associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS’s timing on patient outcomes, based on data from the PREPARE CS registry. (2) Methods: The PREPARE CS prospective registry includes patients who experienced cardiogenic shock (SCAI classes C–E) and were subsequently referred for cardiac catheterization. Our present analysis included a subset of this registry, in whom MCS was used and who underwent coronary intervention due to myocardial infarction. Patients were categorized into an Upfront group and a Procedural group, depending on the timing of MCS’s introduction in relation to their PCI. The endpoint was in-hospital mortality. (3) Results: In total, 71 patients were included. MCS was begun prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after the initiation of PCI (Procedural). The groups’ baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of the Impella^® device compared to extracorporeal membrane oxygenation (67% vs. 33%), while the Procedural group exhibited a balanced use of both (50% vs. 50%). Most patients suffered from multi-vessel disease in both groups (82% vs. 84%, respectively; p = 0.99), and most patients required a complex PCI procedure; the latter was more prevalent in the Upfront group (94% vs. 71%, respectively; p = 0.02). Their rates of complete revascularization were comparable (52% vs. 34%, respectively; p = 0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs. 79%, p < 0.05); however, in-hospital mortality was similar (61% vs. 79%, respectively; p = 0.12). (4) Conclusions: The upfront implantation of MCS in myocardial infarction-associated CS did not provide an in-hospital survival benefit.

(1) Background: Mechanical circulatory support (MCS) in myocardial infarction associated cardiogenic shock is subject to debate. This analysis aims to elucidate the impact of MCS timing on patient outcomes, based on data from the PREPARE CS registry.; (2) Methods: PREPARE CS prospective registry included consecutive patients experiencing cardiogenic shock (SCAI Classes C-E) and were referred for cardiac catheterization. Present analysis included a subset, in whom MCS was used and underwent coronary intervention due to myocardial infarction. Patients were categorized into Upfront group versus Procedural group, depending on the timing of MCS introduction in relation to PCI. Endpoint was the in-hospital mortality; (3) Results: In total 71 patients were included. MCS was started prior to PCI in 33 (46%) patients (Upfront), whereas 38 (54%) received MCS during or after PCI initiation (Procedural). Baseline characteristics and hemodynamic parameters were comparable. The Upfront group had a higher utilization of Impella® device compared to extracorporeal membrane oxygenation (67% vs 33%), while the Procedural group exhibited a balanced use (50% vs 50%). Most patients suffered of multi-vessel disease in both groups (82% vs 84%, respectively; p=0.99) and most patients required complex PCI procedure, the latter was more prevalent in the Upfront group (94% vs 71%, respectively; p=0.02). Rates of complete revascularization were comparable (52% vs 34%, respectively; p=0.16). Procedural CPR was significantly more frequent in the Procedural group (45% vs 79%, p<0.05), still in-hospital mortality was similar (61% vs 79%, respectively; p=0.12); (4) Conclusions: Upfront implantation of MCS in myocardial infarction associated CS did not provide in-hospital survival benefit.