High prevalence and clinical relevance of intrapulmonary vascular dilatations in patients undergoing TIPS implantation.

BACKGROUND AND AIMS: Considerate patient selection is vital to ensure best possible outcomes after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, data regarding the impact of intrapulmonary vascular dilatations (IPVD) or hepatopulmonary syndrome (HPS) on the clinical course after TIPS implantation is lacking. Hence, this study aimed to investigate the relevance of IPVD and HPS in patients undergoing TIPS implantation. METHODS: Contrast enhanced echocardiography and blood gas analysis were utilized to determine presence of IPVD and HPS. Multivariable competing risk analyses were performed to evaluate cardiac decompensation (CD), hepatic decompensation (HD) and liver transplant (LTx)-free survival within one-year of follow up. RESULTS: Overall, 265 patients were included, of whom 136 had IPVD and 71 fulfilled the HPS criteria. Patients with IPVD had lower Freiburg index of post-TIPS survival (FIPS) scores, lower creatinine and more often received a TIPS because of variceal bleeding. Presence of IPVD was associated with a significantly higher incidence of CD (HR: 1.756 95%CI: 1.011-3.048 p=0.046) and HD (HR: 1.841 95%CI: 1.255-2.701 p=0.002). However, LTx-free survival was comparable between patients with and without IPVD (HR: 1.081 95%CI: 0.630-1.855, p=0.780). Patients with HPS displayed a trend towards more CD (HR: 1.708 95%CI: 0.935-3.122, p=0.082) and HD (HR: 1.458 95%CI: 0.934-2.275, p=0.097) that failed to reach statistical significance. LTx-free survival did not differ in those with HPS compared to patients without HPS, respectively (HR: 1.052 95%CI: 0.577-1.921, p=0.870). CONCLUSION: Screening for IPVD before TIPS implantation could help to further identify patients at higher risk of cardiac and hepatic decompensation.

Anterior mitral leaflet laceration using the MitraCut technique for transapical transcatheter Tendyne implantation after unsuccessful Carillon indirect annuloplasty: a case report.

Background: The introduction of a transapical transcatheter beating heart replacement system has significantly expanded therapeutic options for patients with severely diseased mitral valves, particularly those ineligibles for traditional surgery or transcatheter repair. However, challenges, such as left ventricular outflow tract obstruction (LVOT-O) and the risk of dynamic systolic anterior motion (SAM) in cases with elongated anterior mitral leaflet (AML) post-prosthesis implantation, impede the widespread adoption of transcatheter mitral valve replacement (TMVR). Case summary: In 2022, a 75-year-old male with severe mixed-genesis mitral regurgitation (MR) underwent Carillon Mitral Contour System annuloplasty. Recurrent heart failure admissions (New York Heart Association IV) and prohibitive risk for open-heart surgery (European System for Cardiac Operative Risk Evaluation II 8.27%) prompted evaluation for Tendyne TMVR with the MitraCut technique. This beating heart transapical approach involved scissor-mediated splitting of the elongated 27 mm AML, essential for mitigating LVOT-O risk and dynamic SAM. The screening echocardiogram revealed the poorly tethered AML near the thickened septum at the simulated neo-LVOT site. Discussion: This case underscores the intricate management challenges associated with severe MR, highlighting the successful application of the MitraCut technique as a viable alternative in high-risk scenarios. The imperative for further research and clinical studies is emphasized to comprehensively elucidate outcomes and safety parameters, providing valuable insights for refining TMVR applications within this context.

Symptom severity reflected by NYHA grade is independently associated with pruritus in chronic heart failure patients.

BACKGROUND: Pruritus is a symptom profoundly impairing patients' quality of life (QoL). It is a common symptom in chronic heart failure (CHF) patients of yet unknown nature. The aim of this study was to evaluate the risk factors of pruritus in CHF patients. METHODS: For this monocentric, prospective cohort study, CHF patients were recruited and CHF symptoms, comorbidities and drug intake were assessed using a structured report. Additionally, a questionnaire evaluated pruritus symptoms. Detailed medical histories including laboratory test results were retrieved from patient files for all participants. RESULTS: We evaluated data from 550 CHF patients. Of those, 25.3% reported pruritus to occur frequently (3-5 times per week), often (1-2 times per week) or daily. Patients of higher NYHA classes (NYHA III + IV) experienced significantly more pruritus (31.2%) than lower NYHA classes (NYHA I + II) (21.1%, p = 0.024). Patients with pruritus reported disproportionately often concomitant stasis dermatitis (p = 0.026) and chronic lung disease (p = 0.014). Other parameters reflecting cardiac, liver, kidney and thyroid function, as well as medical therapies showed no significant differences between patients with and without pruritus. In the multivariate logistic regression analysis, only NYHA class (p = 0.016, OR 1.55, 95% confidence interval (CI): [1.09; 2.20]) and elevated leukocyte count (p = 0.007, OR 1.11, CI [1.03; 1.21]) remained significantly associated with pruritus in CHF patients. CONCLUSIONS: NYHA class is an independent predictor for pruritus in CHF patients. Besides NYHA class, leukocyte count was also associated with increased pruritus. Pruritus may impair QoL in CHF patients and should thus be included in the assessment of those patients. We suggest that providing best care for CHF patients can be achieved through an interdisciplinary approach of cardiologists and dermatologists and should include a pruritus assessment.

A pilot study for risk stratification of ventricular tachyarrhythmia in hypertrophic cardiomyopathy with routine echocardiography parameters.

Ventricular tachyarrhythmia (VTA) are frequent arrhythmias in patients with hypertrophic cardiomyopathy (HCM). Representing a major risk factor for sudden cardiac death, Holter ECG at first clinical presentation appears insufficient. This study aims to investigate the ability of routinely obtained parameters associated with myocardial remodeling in stratifying for VTA in HCM. In this monocentric analysis, patients with HCM underwent 12-channel electrocardiography and echocardiography, including tissue doppler imaging. The study's primary endpoint was the documentation of non-sustained and sustained ventricular tachycardia-summarized as ventricular tachyarrhythmias (VTA) on Holter ECG or active devices. The occurrence of VTA was exploratory. Based on our collective, we developed a risk model regarding VTA. Of 140 HCM patients, 38 (27.1%) had an episode of VTA. Patients with VTA were likelier to have a history of atrial fibrillation (p < 0.001), a thicker interventricular septum (p < 0.001) and lower peak systolic mitral annular velocity (p < 0.001). The parameters were independently associated with endpoint in univariate and multivariate logistic regression. We created a logistic equation and calculated a cut-off value. The resulting ROC curve revealed a discriminative ability with AUC of 0.80 (sensitivity, 63%; specificity, 88%). Our risk model including these widely available parameters is able to distinguish low and high-risk of VTA in patients with HCM.

Hypoxia Attenuates Pressure Overload-Induced Heart Failure.

BACKGROUND: Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)-induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device-mediated mechanical unloading and circulatory support. METHODS AND RESULTS: We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia-inducible factor)-1α-mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased Tbx5 and increased Hsd11b1 mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia-mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device-mediated myocardial recovery revealed a similar expression pattern for TBX5 and HSD11B1 as observed in HxTAC hearts. CONCLUSIONS: Hypoxia attenuates LVPO-induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia-mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO-induced heart failure and mediate cardiac recovery following mechanical circulatory support.

Multicenter comparison of transcatheter aortic valve implantation with the self-expanding ACURATE neo2 versus Evolut PRO transcatheter heart valves.

BACKGROUND: New-generation self-expanding transcatheter aortic heart valves (THV) were designed to overcome technical constraints of their preceding generations. We sought to compare the efficacy and safety of the self-expanding ACURATE neo2 (Neo2) versus Evolut PRO (PRO) devices. METHODS: Seven hundred nine patients undergoing transfemoral transcatheter aortic valve implantation (TAVI) with either Neo2 (n = 496) or PRO (n = 213) were included. Propensity score matching (PSM) was performed to account for differences in baseline characteristics. In-hospital and 30-day clinical outcomes were evaluated according to Valve Academic Research Consortium-3 criteria. RESULTS: Baseline characteristics were comparable between both groups after PSM (Neo2: n = 155, Evolut Pro: n = 155). Technical success rates were high in both groups (Neo2: 94.8% vs PRO: 97.4%; p = 0.239). Need for permanent pacemaker implantation was less frequent with Neo2 compared with PRO (7.5% vs 20.6%; p = 0.002), whereas major vascular complications were more frequent with Neo2 (Neo2: 11.6% vs PRO: 4.5%; p = 0.022). Intended valve performance at discharge was high in both groups without relevant differences among groups (Neo2: 97.4% vs. 95.3%; p = 0.328). CONCLUSIONS: Short-term outcomes after TAVI using latest-generation self-expanding THV were excellent, with overall low rates of adverse events. However, Neo2 was associated with lower pacemaker rates and reduced the prevalence of moderate-severe paravalvular leakage. Transprosthetic gradients after TAVI were higher with Neo2 compared with PRO.

Diastolic dysfunction is associated with cardiac decompensation after transjugular intrahepatic portosystemic shunt in patients with liver cirrhosis.

BACKGROUND AND AIMS: About 20% of patients develop cardiac decompensation within the first year after transjugular intrahepatic portosystemic shunt (TIPS) insertion. However, risk factors for cardiac decompensation remain poorly defined. We aimed to evaluate predictors of cardiac decompensation after TIPS insertion in a large, well-defined cohort of patients with liver cirrhosis. METHODS: 234 cirrhotic patients who received a TIPS at Hannover Medical School were retrospectively followed up for one year to assess the incidence of cardiac decompensation. Echocardiographic parameters and established diagnostic criteria for cardiac impairment (e.g. by the American Society of Echocardiography/ European Association of Cardiovascular Imaging (ASE/EACVI)) were investigated for an association with cardiac decompensation in a competing risk analysis. Survival was analyzed using a multivariable cox regression analysis adjusting for Freiburg index of post-TIPS survival. RESULTS: Predominant TIPS indication was ascites (83%). Median age was 59 years, median MELD-score 12% and 58% were male. Overall, 41 patients (18%) developed cardiac decompensation within one year after TIPS insertion. Diastolic dysfunction according to the ASE/EACVI was diagnosed in 26% of patients at baseline and was linked to a significantly higher risk for cardiac decompensation (p = 0.025) after TIPS. When investigating individual echocardiographic baseline parameters, only pathological E/A (<0.8 or >2) was identified as a risk factor for cardiac decompensation (p = 0.015). Mortality and liver transplantation (n = 50) were significantly higher among patients who developed cardiac decompensation (HR = 5.29, p < 0.001) as well as in patients with a pathological E/A (HR = 2.34, p = 0.006). Cardiac high-risk status (44% of patients) was strongly linked to cardiac decompensation (HR = 2.93, p = 0.002) and mortality (HR = 2.24, p = 0.012). CONCLUSION: Cardiac decompensation after TIPS is a frequent and important complication and is associated with reduced survival. American Society of Echocardiography/EACVI criteria and E/A seem to be the best parameters to predict the cardiac risk in cirrhotic patients undergoing TIPS insertion.

Simple and safe digitoxin dosing in heart failure based on data from the DIGIT-HF trial.

BACKGROUND: The present study aimed to develop a simple dosing score when starting the cardiac glycoside digitoxin in heart failure with reduced ejection fraction (HFrEF) employing first data from the randomized, double-blinded DIGIT-HF trial. METHODS AND RESULTS: In DIGIT-HF, digitoxin was started with a dose of 0.07 mg once daily (o.d.) in all patients. For score derivation, 317 patients were analyzed who had been randomized to digitoxin. In these patients, after scheduled determination of serum levels at study week 6, the digitoxin dose had remained unchanged or had been reduced to 0.05 mg o.d. (97% of patients) to achieve serum concentrations within a predefined range (10.5-23.6 nmol/l). In logistic regression analyses, sex, age, body mass index (BMI), and estimated glomerular filtration rate (eGFR) were associated with need for dose reduction and, therefore, selected for further developing the dosing score. Optimal cut-points were derived from ROC curve analyses. Finally, female sex, age ≥ 75 years, eGFR < 50 ml/min/1.73 m2, and BMI < 27 kg/m2 each were assigned one point for the digitoxin dosing score. A score of ≥ 1 indicated the need for dose reduction with sensitivity/specificity of 81.6%/49.7%, respectively. Accuracy was confirmed in a validation data set including 64 patients randomized to digitoxin yielding sensitivity/specificity of 87.5%/37.5%, respectively. CONCLUSION: In patients with HFrEF, treatment with digitoxin should be started at 0.05 mg o.d. in subjects with either female sex, eGFR < 50 ml/min/1.73m2, BMI < 27 kg/m2, or age ≥ 75 years. In any other patient, digitoxin may be safely started at 0.07 mg o.d.

Immune Checkpoint Inhibitor Associated Myocarditis and Cardiomyopathy: A Translational Review.

Immune checkpoint inhibitors (ICIs) have revolutionized oncology and transformed the treatment of various malignancies. By unleashing the natural immunological brake of the immune system, ICIs were initially considered an effective, gentle therapy with few side effects. However, accumulated clinical knowledge reveals that ICIs are associated with inflammation and tissue damage in multiple organs, leading to immune-related adverse effects (irAEs). Most irAEs involve the skin and gastrointestinal tract; however, cardiovascular involvement is associated with very high mortality rates, and its underlying pathomechanisms are poorly understood. Ranging from acute myocarditis to chronic cardiomyopathies, ICI-induced cardiotoxicity can present in various forms and entities. Revealing the inciting factors, understanding the pathogenesis, and identifying effective treatment strategies are needed to improve the care of tumor patients and our understanding of the immune and cardiovascular systems.

Prevalence of HSPB6 gene variants in peripartum cardiomyopathy: Data from the German PPCM registry.

BACKGROUND: Heat shock protein family B (small) member 6 (HSPB6) mediates cardioprotective effects against stress-induced injury. In humans two gene variants of HSPB6 have been identified with a prevalence of 1% in patients with dilated cardiomyopathy (DCM). Peripartum cardiomyopathy (PPCM) is a potentially life-threatening heart disease of unknown etiology in previously healthy women of whom 16-20% of PPCM carry gene variants associated with cardiomyopathy. This study was designed to analyze the prevalence of pathogenic HSPB6 gene variants in PPCM. METHODS AND RESULTS: Whole-exome sequencing was performed in whole blood samples of PPCM patients (n = 65 PPCM patients from the German PPCM registry) and screened subsequently for HSPB6 gene variants. In this PPCM cohort one PPCM patient carries a HSPB6 gene variant of uncertain significance (VUS), which was not associated with changes in the amino acid sequence and no likely pathogenic or pathogenic variants were detected. CONCLUSION: HSPB6 gene variants did not occur more frequently in a cohort of PPCM patients from the German PPCM registry, compared to DCM patients. Genetic analyses in larger cohorts and in cohorts of different ethiologies of PPCM patients are needed to address the role of the genetic background in the pathogenesis of PPCM.

Cabergoline treatment promotes myocardial recovery in peripartum cardiomyopathy.

AIMS: Peripartum cardiomyopathy (PPCM) is a rare heart disease, occurring in previously heart-healthy women during the last month of pregnancy or the first months after delivery due to left ventricular (LV) systolic dysfunction. A common pathomechanistic pathway of PPCM includes increased oxidative stress and the subsequent generation of a cleaved prolactin fragment (16 kDa PRL), which promotes the onset of heart failure (HF) in a microRNA (miR)-146a-dependent manner. Inhibition of prolactin secretion with the dopamine D2 receptor (D2R) agonist bromocriptine combined with standard HF therapy supports cardiac recovery. This study examined whether treatment with the more selective D2R agonist cabergoline prevents HF development in an experimental PPCM mouse model and might be used as an alternative treatment regime for PPCM. METHODS AND RESULTS: Postpartum (PP) female PPCM-prone mice with a cardiomyocyte restricted STAT3-deficiency (αMHC-Cretg/+ ; Stat3fl/fl ; CKO) were treated over two consecutive nursing periods with cabergoline (CKO Cab, 0.5 mg/kg/day) and were compared with bromocriptine treated CKO (CKO Br) and postpartum-matched WT and CKO mice. Cabergoline treatment in CKO PP mice preserved cardiac function [fractional shortening (FS): CKO Cab: 34.5 ± 9.4% vs. CKO: 22.1 ± 9%, P < 0.05] and prevented the development of cardiac hypertrophy, fibrosis, and inflammation as effective as bromocriptine therapy (FS: CKO Br: 33.4 ± 5.6%). The myocardial up-regulation of the PPCM biomarkers plasminogen inhibitor activator 1 (PAI-1) and miR-146a were prevented by both cabergoline and bromocriptine therapy. A small cohort of three PPCM patients from the German PPCM Registry was treated with cabergoline (1 mg per week for 2 weeks, followed by 0.5 mg per week for another 6 weeks) due to a temporary unavailability of bromocriptine. All PPCM patients initially presented with a severely reduced LV ejection fraction (LVEF: 26 ± 2%). However, at 6 months of follow-up, LV function (LVEF: 56 ± 2%) fully recovered in all three PPCM patients, and no adverse events were detected. CONCLUSIONS: In the experimental PPCM mouse model, the selective D2R agonist cabergoline prevents the onset of postpartum HF similar to bromocriptine. In PPCM patients, cabergoline treatment was safe and effective as all patients fully recovered. Cabergoline might serve as a promising alternative to bromocriptine. However, these findings are based on experimental data and a small case series and thus have to be interpreted with caution and should be validated in a larger clinical trial.

High prevalence of reduced fertility and use of assisted reproductive technology in a German cohort of patients with peripartum cardiomyopathy.

BACKGROUND: Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet. METHODS: A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population. RESULTS: The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p < 0.0001), the percentage of born infants conceived by IVF/ICSI was higher (p < 0.0001) with a higher multiple birth (p < 0.0001), C-section (p < 0.0001) and preeclampsia rate (p < 0.0001), compared to postpartum women. The cardiac outcome was comparable between subfertile and fertile PPCM patients. Whole exome sequencing in a subset of n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome. CONCLUSIONS: Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure.

Clinical characteristics and long-term outcomes in patients with peripartum cardiomyopathy (PPCM) receiving left ventricular assist devices (LVAD).

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare cause of heart failure (HF), presenting with left ventricular (LV) systolic dysfunction either at the end of pregnancy or in the months following delivery. In rare cases, PPCM leads to severe impairment of LV function, refractory cardiogenic shock or advanced HF. LV assist devices (LVAD) have been shown to be a feasible treatment option in advanced HF. However, little is known about long-term outcomes and prognosis of PPCM patients undergoing LVAD implantation. METHODS: A retrospective analysis of data from PPCM patients undergoing LVAD implantation in two tertiary centers with respect to long-term outcomes was performed. RESULTS: Twelve patients of median age 30 (18-39) years were included. Eight patients were experiencing cardiogenic shock (INTERMACS 1) at implantation. Seven patients were implanted within 1 month of their PPCM diagnosis. Median duration of LVAD support was 19 (2-92) months with median follow up of 67 (18-136) months (100% complete). In-hospital and 1-year mortality were 0% and 8.3%, respectively. Two patients died on LVAD support, four patients were successfully bridged to transplantation, two patients are still on LVAD, and four were successfully weaned due to sufficient LV recovery (one died after LV function deteriorated again). CONCLUSION: LVAD treatment of decompensated end-stage PPCM is feasible. Early LVAD provision led to hemodynamic stabilization in our cohort and facilitated safe LV recovery in one third of these young female patients.

Echocardiographic parameters indicating left atrial reverse remodeling after catheter ablation for atrial fibrillation.

Background: The echocardiographic parameters total atrial conduction time (PA-TDI duration), left atrial (LA) volume index (LAVI), and LA strain reflect adverse atrial remodeling and predict atrial fibrillation (AF). Objectives: The aim of this study was to investigate echocardiographic parameters indicating reverse LA remodeling and potential associations with AF recurrence after pulmonary vein isolation (PVI). Methods: This prospective observational study consecutively enrolled patients scheduled for PVI for symptomatic AF. Electrocardiogram (ECG) test and transthoracic echocardiography were performed the day before and after PVI and again 3 months later. AF recurrence was determined by Holter ECG at 3 months, and telephone follow-up at 12 months, after PVI. The parameters of LA remodeling [PA-TDI, LAVI, and LA strain analysis: reservoir strain (LASr), conduit strain (LAScd), contraction strain (LASct)] were determined by transthoracic echocardiography. Results: A total of 48 patients were included in the study (mean age: 61.4 ± 12.2 years). PA-TDI significantly decreased the day after PVI compared with the baseline (septal PA-TDI 103 ± 13 vs. 82 ± 14.9 ms, p ≤ 0.001; lateral PA-TDI 122.4 ± 14.8 vs. 106.9 ± 14.4 ms, p ≤ 0.001) and at the 3-month follow-up (septal PA-TDI: 77.8 ± 14.5, p ≤ 0.001; lateral PA-TDI 105.2 ± 16.1, p ≤ 0.001). LAVI showed a significant reduction at the 3-month follow-up compared with the baseline (47.7 ± 14.4 vs. 40.5 ± 9.7, p < 0.05). LASr, LAScd, and LASct did not change after PVI compared with the baseline. AF recurred in 10 patients after PVI (21%). Septal PA-TDI, septal a', and LAVI/a' determined the day after PVI were associated with AF recurrence. Conclusion: Changes in echocardiographic parameters of LA remodeling and function indicate that functional electromechanical recovery preceded morphological reverse remodeling of the left atrium after PVI. Furthermore, these changes in echocardiographic parameters indicating LA reverse remodeling after PVI may identify patients at high risk of AF recurrence.

Acute echocardiographic and electrocardiographic effects of triggered left ventricular pacing.

Cardiac resynchronization therapy (CRT) is an essential pillar in the therapy of heart failure patients with reduced ejection fraction (HFrEF) presenting with broad left bundle branch block (LBBB) or pacemaker dependency. To achieve beneficial effects, CRT requires high bi-ventricular (BiV) pacing rates. Therefore, device-manufacturers designed pacing algorithms which maintain high BiV pacing rates by a left ventricular (LV) pacing stimulus immediately following a right ventricular sensed beat. However, data on clinical impact of these algorithms are sparse. We studied 17 patients implanted with a CRT device providing triggered left ventricular pacing (tLVp) in case of atrioventricular nodal conduction. Assessment of LV dyssynchrony was performed using echocardiographic and electrocardiographic examination while CRT-devices were set to three different settings: 1. Optimized bi-ventricular-stimulation (BiV); 2. Physiological AV nodal conduction (tLVp-off); 3. Physiological AV nodal conduction and tLVp-algorithm turned on (tLVp-on). QRS duration increased when the CRT-device was set to tLVp-off compared to BiV-Stim, while QRS duration was comparable to BiV-Stim with the tLVp-on setting. Echocardiographic analysis revealed higher dyssynchrony during tLVp-off compared to BiV-Stim. TLVp-on did not improve LV dyssynchrony compared to tLVp-off. QRS duration significantly decreased using tLVp-algorithms compared to physiological AV nodal conduction. However, echocardiographic examination could not show functional benefit from tLVp-algorithms, suggesting that these algorithms are inferior to regular biventricular pacing regarding cardiac resynchronization. Therefore, medical treatment and ablation procedures should be preferred, when biventricular pacing rates have to be increased. TLVp-algorithms can be used in addition to these treatment options.

[Peripartum Cardiomyopathy]. / Peripartale Kardiomyopathie.

Peripartum cardiomyopathy (PPCM) is a rare but potentially life-threatening heart disease, with onset in the last month of pregnancy or in the first months after delivery in previously heart-healthy women. PPCM patients typically present with heart failure due to left ventricular (LV) dysfunction with an LV ejection fraction (EF) < 45 %. In the last years clinical and experimental studies contributed to a better understanding of the pathophysiology and the clinical course of PPCM. In the context of oxidative stress, the nursing hormone prolactin is cleaved into a smaller antiangiogenic and proapoptotic 16k Da form, leading to myocardial dysfunction. In an animal model this can be prevented by treatment with the dopamine agonist bromocriptine, which suppresses prolactin release. This therapeutic approach was confirmed in several clinical studies. Therefore, the current guidelines recommend a treatment consisting of a heart failure treatment according to current guidelines in combination with the dopamine agonist bromocriptine. If the diagnosis is made early and the treatment is started immediately, the prognosis is good compared to other forms of cardiomyopathies, as LV function recovers in most cases.In the acute phase the severity of heart failure differs among PPCM patients. Some patients present with mild forms, whereas some PPCM patients display severely reduced LV function and cardiogenic shock. Especially the latter cases are still challenging, as treatment with ß1-adrenergic receptor agonists is associated with progression of heart failure and a worse cardiac outcome. Therefore, patients with cardiogenic shock complicating PPCM should be treated in centers experienced in mechanical circulatory support in combination with bromocriptine treatment.

Increased Late Noncardiac Nonrelapse Mortality in Patients with Atrial Fibrillation Diagnosed During Their Hospital Stay for Allogeneic Stem Cell Transplantation.

Atrial fibrillation (AF) is the most common arrhythmia in adults but its impact on allogeneic stem cell transplantation (SCT) is not well characterized. We studied AF manifestation during the hospital stay for allogeneic SCT, referred to as AF in hospital (AFiH), and analyzed the incidence of, risk factors for, and clinical impact of AFiH on intensive care unit (ICU)-/hospital-/ and overall survival (OS), relapse-free survival (RFS), nonrelapse mortality (NRM), and graft-versus-host disease (GVHD)-free, relapse-free survival (GRFS). This retrospective matched cohort study comprised 553 consecutive SCT recipients at Hannover Medical School between January 2013 and October 2019. Patients with AFiH were compared with a non-AFiH control cohort matched for Hematopoietic Stem Cell-Specific Comorbidity Index (HCT-CI), European Group for Blood and Marrow Transplantation (EBMT) risk score, disease, conditioning regimen and availability of molecular genetic data for patients with myeloid diseases. AFiH occurred in 46 patients (8%) at a median of 2 days (interquartile range, 0 to 8 days) after SCT. Patient history of AF and elevated NT-proBNP and high-sensitivity troponin T levels, but not conventional echocardiographic parameters, were predictive for AFiH. AFiH occurred more often in patients with mutations in DNMT3A, TET2, and ASXL1 genes related to clonal hematopoiesis compared with patients with wild-type alleles, with the greatest impact from DMT3A mutations. ICU admission was significantly higher in the AFiH cohort (46% versus 7%), without significant differences in ICU or post-ICU hospital survival (62% versus 40% and 52% versus 40%, respectively). The main cause of death was sepsis. In terms of long-term outcomes, the incidences of relapse and grade II-IV acute GVHD did not differ significantly between the AFiH and the non-AFiH groups; however, OS was significantly shorter in the AFiH group (1 year OS, 39% versus 65%), owing to late noncardiac NRM (1 year NRM, 49% versus 27%). Although the underlying cellular and molecular mechanisms remain to be characterized in further detail, these data clearly demonstrate the impact of inpatient AF manifestation/AFiH on long-term outcomes of SCT recipients.

Right Ventricular Function Improves Early After Percutaneous Mitral Valve Repair in Patients Suffering From Severe Mitral Regurgitation.

Background: Percutaneous mitral valve edge-to-edge procedure (PMVR) using the MitraClip® system (Abbot Vascular, CA) is an established therapy for severe mitral regurgitation (MR) in patients judged inoperable or at high surgical risk. Besides determining exercise capacity, right ventricular (RV) function has prognostic value in heart failure and after cardiac surgery. We therefore investigated the impact of PMVR on RV function in patients with severe MR. Methods and Results: Sixty-three patients undergoing PMVR at our department were prospectively enrolled. Transthoracic echocardiography was performed before, early (2-12d) after PMVR and after 3 months, including advanced echocardiographic analyses such as 3D imaging and strain analyses. At baseline, all patients presented with advanced heart failure symptoms. Etiology of MR was more often secondary and, if present, left ventricular (LV) dysfunction was predominantly caused by ischemic cardiomyopathy. PMVR substantially reduced MR to a grade ≤ 2 in most patients. Echocardiographic assessment revealed a largely unchanged LV systolic function early after PMVR, while in contrast RV function substantially improved after PMVR [3D RV EF (%): pre 33.7% [27.4; 39.6], post 40.0% [34.5; 46.0] (p < 0.01 vs. pre), 3 months 42.8% [38.3; 48.1] (p < 0.01 vs. pre); 2D RV GLS (%): pre -12.9% [-14.5; -10.5], post -16.0% [-17.9; -12.6] (p < 0.01 vs. pre), 3 months -17.2% [-21.7; -14.9] (p < 0.01 vs. pre)]. Factors that attenuated RV improvement were larger ventricular volumes, lower LV function, secondary MR, and a higher STS score (all p < 0.05). Conclusion: By using advanced echocardiographic parameters, we discovered an early improvement of RV function after PMVR that is preserved for months, independent from changes in LV function. Improvement of RV function was less pronounced in patients presenting with an advanced stage of heart failure and a higher burden of comorbidities reflected by the STS score.