Spontaneous pregnancy-associated coronary artery dissection: a case report on diagnostic and therapeutic challenges.

Background: One of the main causes of myocardial infarction during pregnancy is spontaneous coronary artery dissection. This is ascribed to hormonal changes during pregnancy leading to a weakening of the vessel wall and haemodynamic changes especially during childbirth. Management options include conservative medical treatment and percutaneous coronary intervention, depending on clinical presentation. Case summary: A 37-year-old woman presented with typical chest pain six weeks after giving birth to her third child. Echocardiography revealed a moderate reduction in systolic function. Initial invasive coronary angiography showed no abnormalities. After cardiac magnetic resonance demonstrated extensive scar, invasive coronary angiography was repeated including intravascular imaging. A dissection of the left anterior descending artery was visualized and treated by percutaneous coronary intervention and stenting. Left ventricular function was normalized at three-month follow-up. In this educational case report, we highlight the diagnostic and therapeutic challenges when treating this special patient cohort and the importance of cardiovascular imaging. Discussion: Pregnancy-associated spontaneous coronary dissection is a potential differential diagnosis when treating post-partum women with recent onset chest pain. Management is challenging and intravascular imaging to visualize dissection should be performed during invasive coronary angiography. Patients require interdisciplinary care within a pregnancy heart team.

Oral Anticoagulants after Heart Transplantation-Comparison between Vitamin K Antagonists and Direct Oral Anticoagulants.

AIMS: Patients after heart transplantation (HTX) often require oral anticoagulants (OACs) due to atrial arrhythmias or thromboembolic events but little is known about the post-transplant use of direct oral anticoagulants (DOACs). We investigated the frequency, indications, and complications of DOACs and vitamin K antagonists (VKAs) after HTX. METHODS: We screened all adult patients for the use of post-transplant OACs who underwent HTX at Heidelberg Heart Center between 2000 and 2021. Patients were stratified by type of OAC (DOAC or VKA) and by DOAC agents (apixaban, dabigatran, edoxaban, or rivaroxaban). Indications for OACs comprised atrial fibrillation, atrial flutter, pulmonary embolism, upper and lower extremity deep vein thrombosis, as well as intracardiac thrombus. RESULTS: A total of 115 of 459 HTX recipients (25.1%) required OACs, including 60 patients with DOACs (52.2%) and 55 patients with VKAs (47.8%). Concerning DOACs, 28 patients were treated with rivaroxaban (46.7%), 27 patients with apixaban (45.0%), and 5 patients with edoxaban (8.3%). We found no significant differences between both groups concerning demographics, immunosuppressive drugs, concomitant medications, indications for OACs, ischemic stroke, thromboembolic events, or OAC-related death. Patients with DOACs after HTX had a significantly lower one-year rate of overall bleeding complications (p = 0.002) and a significantly lower one-year rate of gastrointestinal hemorrhage (p = 0.011) compared to patients with VKAs after HTX in the Kaplan-Meier estimator. CONCLUSIONS: DOACs were comparable to VKAs concerning the risk of ischemic stroke, thromboembolic events, or OAC-related death but were associated with significantly fewer bleeding complications in HTX recipients.

Frequency, Risk Factors, and Clinical Outcomes of Late-Onset Atrial Flutter in Patients after Heart Transplantation.

Aims: Atrial flutter (AFL) is a common late-onset complication after heart transplantation (HTX) and is associated with worse clinical outcomes. Methods: This study investigated the frequency, risk factors, and outcomes of late-onset post-transplant AFL. We analyzed 639 adult patients undergoing HTX at the Heidelberg Heart Center between 1989 and 2019. Patients were stratified by diagnosis and type of late-onset post-transplant AFL (>90 days after HTX). Results: A total of 55 patients (8.6%) were diagnosed with late-onset post-transplant AFL, 30 had typical AFL (54.5%) and 25 had atypical AFL (45.5%). Patients with AFL were younger at HTX (p = 0.028), received more biatrial anastomosis (p = 0.001), and presented with moderate or severe tricuspid regurgitation (56.4%). Typical AFL was associated with graft rejection (p = 0.016), whereas atypical AFL was associated with coronary artery disease (p = 0.028) and stent implantation (p = 0.042). Patients with atypical AFL showed a higher all-cause 1-year mortality (p = 0.010) along with a higher rate of graft failure after diagnosis of AFL (p = 0.023). Recurrence of AFL was high (83.6%). Patients with catheter ablation after AFL recurrence had a higher 1-year freedom from AFL (p = 0.003). Conclusions: Patients with late-onset post-transplant AFL were younger at HTX, received more biatrial anastomosis, and showed a higher rate of moderate or severe tricuspid regurgitation. Typical AFL was associated with graft rejection, whereas atypical AFL was associated with myocardial ischemia, graft failure, and mortality. Catheter ablation represents a viable option to avoid further episodes of late-onset AFL after HTX.

Genotype Complements the Phenotype: Identification of the Pathogenicity of an LMNA Splice Variant by Nanopore Long-Read Sequencing in a Large DCM Family.

Dilated cardiomyopathy (DCM) is a common cause of heart failure (HF) and is of familial origin in 20−40% of cases. Genetic testing by next-generation sequencing (NGS) has yielded a definite diagnosis in many cases; however, some remain elusive. In this study, we used a combination of NGS, human-induced pluripotent-stem-cell-derived cardiomyocytes (iPSC-CMs) and nanopore long-read sequencing to identify the causal variant in a multi-generational pedigree of DCM. A four-generation family with familial DCM was investigated. Next-generation sequencing (NGS) was performed on 22 family members. Skin biopsies from two affected family members were used to generate iPSCs, which were then differentiated into iPSC-CMs. Short-read RNA sequencing was used for the evaluation of the target gene expression, and long-read RNA nanopore sequencing was used to evaluate the relevance of the splice variants. The pedigree suggested a highly penetrant, autosomal dominant mode of inheritance. The phenotype of the family was suggestive of laminopathy, but previous genetic testing using both Sanger and panel sequencing only yielded conflicting evidence for LMNA p.R644C (rs142000963), which was not fully segregated. By re-sequencing four additional affected family members, further non-coding LMNA variants could be detected: rs149339264, rs199686967, rs201379016, and rs794728589. To explore the roles of these variants, iPSC-CMs were generated. RNA sequencing showed the LMNA expression levels to be significantly lower in the iPSC-CMs of the LMNA variant carriers. We demonstrated a dysregulated sarcomeric structure and altered calcium homeostasis in the iPSC-CMs of the LMNA variant carriers. Using targeted nanopore long-read sequencing, we revealed the biological significance of the variant c.356+1G>A, which generates a novel 5' splice site in exon 1 of the cardiac isomer of LMNA, causing a nonsense mRNA product with almost complete RNA decay and haploinsufficiency. Using novel molecular analysis and nanopore technology, we demonstrated the pathogenesis of the rs794728589 (c.356+1G>A) splice variant in LMNA. This study highlights the importance of precise diagnostics in the clinical management and workup of cardiomyopathies.

Pre-transplant Type 2 Diabetes Mellitus Is Associated With Higher Graft Failure and Increased 5-Year Mortality After Heart Transplantation.

Aims: Cardiac transplant recipients often suffer from type 2 diabetes mellitus (T2DM) but its influence on graft failure and post-transplant mortality remains unknown. The aim of this study was to investigate the long-term effects of pre-transplant T2DM in patients after heart transplantation (HTX). Methods: This study included a total of 376 adult patients who received HTX at Heidelberg Heart Center between 01/01/2000 and 01/10/2016. HTX recipients were stratified by diagnosis of T2DM at the time of HTX. Patients with T2DM were further subdivided by hemoglobin A1c (HbA1c ≥ 7.0%). Analysis included donor and recipient data, immunosuppressive drugs, concomitant medications, post-transplant mortality, and causes of death. Five-year post-transplant mortality was further assessed by multivariate analysis (Cox regression) and Kaplan-Meier estimator. Results: About one-third of all HTX recipients had T2DM (121 of 376 [32.2%]). Patients with T2DM showed an increased 5-year post-transplant mortality (41.3% versus 29.8%; P = 0.027) and had a higher percentage of death due to graft failure (14.9% versus 7.8%; P = 0.035). Multivariate analysis showed T2DM (HR: 1.563; 95% CI: 1.053-2.319; P = 0.027) as an independent risk factor for 5-year mortality after HTX. Kaplan-Meier analysis showed a significantly better 5-year post-transplant survival of patients with T2DM and a HbA1c < 7.0% than patients with T2DM and a HbA1c ≥ 7.0% (68.7% versus 46.3%; P = 0.008) emphasizing the clinical relevance of a well-controlled T2DM in HTX recipients. Conclusion: Pre-transplant T2DM is associated with higher graft failure and increased 5-year mortality after HTX.

Five-year results of heart rate control with ivabradine or metoprolol succinate in patients after heart transplantation.

BACKGROUND: Cardiac graft denervation causes inadequate sinus tachycardia in patients after heart transplantation (HTX) which is associated with reduced survival. This study investigated the 5-year results of heart rate control with ivabradine or metoprolol succinate in patients after HTX. METHODS: This registry study analyzed 104 patients receiving either ivabradine (n = 50) or metoprolol succinate (n = 54) within 5 years after HTX. Analysis included patient characteristics, medication, echocardiographic features, cardiac catheterization data, cardiac biomarkers, heart rates, and post-transplant survival including causes of death. RESULTS: Demographics and post-transplant medication revealed no significant differences except for ivabradine and metoprolol succinate use. At 5-year follow-up, patients with ivabradine had a significantly lower heart rate (73.3 bpm) compared to baseline (88.6 bpm; P < 0.01) and to metoprolol succinate (80.4 bpm; P < 0.01), a reduced left ventricular mass (154.8 g) compared to baseline (179.5 g; P < 0.01) and to metoprolol succinate (177.3 g; P < 0.01), a lower left ventricular end-diastolic pressure (LVEDP; 12.0 mmHg) compared to baseline (15.5 mmHg; P < 0.01) and to metoprolol succinate (17.1 mmHg; P < 0.01), and a reduced NT-proBNP level (525.4 pg/ml) compared to baseline (3826.3 pg/ml; P < 0.01) and to metoprolol succinate (1038.9 pg/ml; P < 0.01). Five-year post-transplant survival was significantly better in patients with ivabradine (90.0%) versus metoprolol succinate (68.5%; P < 0.01). CONCLUSION: Patients receiving ivabradine showed a superior heart rate reduction and a better left ventricular diastolic function along with an improved 5-year survival after HTX.

Risk Factors, Treatment and Prognosis of Patients with Lung Cancer after Heart Transplantation.

Long-term survival after heart transplantation (HTX) is impacted by adverse effects of immunosuppressive pharmacotherapy, and post-transplant lung cancer is a common occurrence. This study aimed to examine the risk factors, treatment, and prognosis of patients with post-transplant lung cancer. We included 625 adult patients who received HTX at Heidelberg Heart Center between 1989 and 2018. Patients were stratified by diagnosis and staging of lung cancer after HTX. Analysis comprised donor and recipient characteristics, medications including immunosuppressive drugs, and survival after diagnosis of lung cancer. A total of 41 patients (6.6%) were diagnosed with lung cancer after HTX, 13 patients received curative care and 28 patients had palliative care. Mean time from HTX until diagnosis of lung cancer was 8.6 ± 4.0 years and 1.8 ± 2.7 years from diagnosis of lung cancer until last follow-up. Twenty-four patients (58.5%) were switched to an mTOR-inhibitor after diagnosis of lung cancer. Multivariate analysis showed recipient age (HR: 1.05; CI: 1.01-1.10; p = 0.02), COPD (HR: 3.72; CI: 1.88-7.37; p < 0.01), and history of smoking (HR: 20.39; CI: 2.73-152.13; p < 0.01) as risk factors for post-transplant lung cancer. Patients in stages I and II had a significantly better 1-year (100.0% versus 3.6%), 2-year (69.2% versus 0.0%), and 5-year survival (53.8% versus 0.0%) than patients in stages III and IV (p < 0.01). Given the poor prognosis of late-stage post-transplant lung cancer, routine reassessment of current smoking status, providing smoking cessation support, and intensified lung cancer screening in high-risk HTX recipients are advisable.

Atrial fibrillation before heart transplantation is a risk factor for post-transplant atrial fibrillation and mortality.

AIMS: Atrial fibrillation (AF) after heart transplantation (HTX) is associated with worse clinical outcomes. The current study aimed to analyse the association between AF before HTX and AF within 30 days after HTX. METHODS AND RESULTS: This study included 639 adults who received HTX at Heidelberg Heart Center. Patients were subdivided into four groups depending on the status of AF before and after HTX. Analyses comprised recipient and donor data, medication, echocardiographic features, permanent pacemaker implantation, stroke, and mortality after HTX. Three hundred thirty-two patients (52.0%) had neither AF before nor after HTX, 15 patients (2.3%) had no AF before HTX but showed AF after HTX, 219 patients (34.3%) showed AF before HTX but had no AF after HTX, and 73 patients (11.4%) had AF before and after HTX. Patients with AF before and after HTX had a higher 1 year post-transplant mortality (39.7%) than patients without AF before or after HTX (18.1%, P < 0.01). Secondary outcomes showed a higher percentage of enlarged atria, ventricular dysfunction, mitral regurgitation, 1-year stroke, and 1-year permanent pacemaker implantation in patients with AF before and after HTX. Multivariate analysis revealed a six-fold elevated risk for post-transplant AF in patients with AF before HTX (hazard ratio: 6.59, confidence interval: 3.72-11.65; P < 0.01). Further risk factors for post-transplant AF were higher donor age and prolonged ischaemic time, whereas total orthotopic HTX was associated with a two-fold lower risk for post-transplant AF. CONCLUSIONS: Atrial fibrillation before HTX is a risk factor for post-transplant AF, permanent pacemaker implantation, and mortality after HTX.

Newly acquired complete right bundle branch block early after heart transplantation is associated with lower survival.

AIMS: Right bundle branch block (RBBB) after heart transplantation (HTX) is a common finding, but its impact on post-transplant survival remains uncertain. This study investigated the post-transplant outcomes of patients with complete RBBB (cRBBB) ≤ 30 days after HTX. METHODS: This registry study analysed 639 patients receiving HTX at Heidelberg Heart Center between 1989 and 2019. Patients were stratified by diagnosis of cRBBB ≤ 30 days after HTX. Analysis included recipient and donor data, medication, echocardiographic features, graft rejections, atrial fibrillation, heart rates, permanent pacemaker implantation and mortality after HTX including causes of death. RESULTS: One hundred thirty-nine patients showed cRBBB ≤ 30 days after HTX (21.8%), 20 patients with pre-existing cRBBB in the donor heart (3.2%) and 119 patients with newly acquired cRBBB (18.6%). Patients with newly acquired cRBBB had a worse 1-year post-transplant survival (36.1%, P < 0.01) compared with patients with pre-existing cRBBB (85.0%) or without cRBBB (86.4%), along with a higher percentage of death due to graft failure (P < 0.01). Multivariate analysis indicated cRBBB ≤ 30 days after HTX as significant risk factor for 1-year mortality after HTX (HR: 2.20; 95% CI: 1.68-2.87; P < 0.01). Secondary outcomes showed a higher rate of an enlarged right atrium (P = 0.01), enlarged right ventricle (P < 0.01), reduced right ventricular function (P < 0.01), 30-day atrial fibrillation (P < 0.01) and 1-year permanent pacemaker implantation (P = 0.02) in patients with cRBBB after HTX. CONCLUSIONS: Newly acquired cRBBB early after HTX is associated with increased post-transplant mortality.

The diagnostic benefit of 16S rDNA PCR examination of infective endocarditis heart valves: a cohort study of 146 surgical cases confirmed by histopathology.

AIMS: Upon suspicion of infective endocarditis, the causative microorganism must be identified to optimize treatment. Blood cultures and culturing of removed valves are the mainstay of this diagnosis and should be complemented by growth-independent methods. We assessed the diagnostic benefit of examining removed endocarditis valves by broad-range bacterial PCR to detect causative bacteria in cases where culturing was not available, negative, or inconclusive because a skin commensal was detected, in patients from our clinical routine practice. METHODS AND RESULTS: Patients from Heidelberg University Hospital with suspicion of endocarditis, followed by valve replacement and analysis by 16S rDNA PCR, between 2015 and 2018, were evaluated. 146 patients with definite infective endocarditis, confirmed by the valve macroscopics and/or histology, were included. Valve PCRs were compared to corresponding blood and valve culture results. Overall, valve PCR yielded an additional diagnostic benefit in 34 of 146 cases (23%) and was found to be more sensitive than valve culture. In 19 of 38 patients with both negative blood and valve cultures, valve PCR was the only method rendering a pathogen. In 23 patients with positive blood cultures detecting skin commensals, 4 patients showed discordant valve PCR results, detecting a more plausible pathogen, and in 11 of 23 cases, valve PCR confirmed commensals in blood culture as true pathogens. Only the remaining 8 patients had negative valve PCRs. CONCLUSION: Valve PCR was found to be a valuable diagnostic tool in surgical endocarditis cases with negative blood cultures or positive blood cultures of unknown significance. TRIAL REGISTRATION: S-440/2017 on 28.08.2017 retrospectively registered. Subdividing of all infective endocarditis patients in this study, showing that valve PCR yields valuable information for patients with skin commensals in blood cultures, which were either confirmed by the same detection in valve PCR or refuted by the detection of a different and typical pathogen in valve PCR. Additionally, benefit was determined in patients with negative or not available blood cultures and only positive detection in valve PCR. +: Positive; -: negative; n/a: not available results.

Combined amiodarone and digitalis therapy before heart transplantation is associated with increased post-transplant mortality.

AIMS: Amiodarone and digitalis are frequently used drugs in patients with heart failure. Both have separately been linked to reduced post-transplant survival, but their combined impact on mortality after HTX remains uncertain. This study investigated the effects of combined amiodarone and digitalis use before HTX on post-transplant outcomes. METHODS AND RESULTS: This registry study analysed 600 patients receiving HTX at Heidelberg Heart Center between 1989 and 2016. Patients were stratified by amiodarone and digitalis use before HTX. Analysis included patient characteristics, medication, echocardiographic features, heart rates, permanent pacemaker implantation, atrial fibrillation, and post-transplant survival including causes of death. One hundred eighteen patients received amiodarone before HTX (19.7%), hereof 67 patients with digitalis (56.8%) and 51 patients without digitalis before HTX (43.2%). Patients with and without amiodarone before HTX showed a similar 1 year post-transplant survival (72.0% vs. 78.4%, P = 0.11), but patients with combined amiodarone and digitalis before HTX had a worse 1 year post-transplant survival (64.2%, P = 0.01), along with a higher percentage of death due to transplant failure (P = 0.03). Echocardiographic analysis of these patients showed a higher percentage of an enlarged right ventricle (P = 0.02), left atrium (P = 0.02), left ventricle (P = 0.03), and a higher rate of reduced left ventricular ejection fraction (P = 0.03). Multivariate analysis indicated combined amiodarone and digitalis use before HTX as a significant risk factor for 1 year mortality after HTX (hazard ratio: 1.69; 95% confidence interval: 1.02-2.77; P = 0.04). CONCLUSIONS: Combined pre-transplant amiodarone and digitalis therapy is associated with increased post-transplant mortality.

Elevated pre-transplant pulmonary vascular resistance is associated with early post-transplant atrial fibrillation and mortality.

AIMS: Severely elevated pre-transplant pulmonary vascular resistance (PVR) has been linked to adverse effects after heart transplantation (HTX). The impact of a moderately increased PVR before HTX on post-transplant outcomes remains uncertain. The aim of this study was to investigate the effects of an elevated pre-transplant PVR ≥ 300 dyn·s·cm-5 (≥3.75 Wood units) on outcomes after HTX. METHODS AND RESULTS: This observational retrospective single-centre study included 561 patients receiving HTX at Heidelberg Heart Center between 1989 and 2015. Patients were stratified by degree of pre-transplant PVR. Analyses covered demographics, post-transplant medication, mortality and causes of death after HTX, early post-transplant atrial fibrillation (AF), and length of the initial hospital stay after HTX. Ninety-four patients (16.8%) had a PVR ≥ 300 dyn·s·cm-5 (≥3.75 Wood units). These patients had a higher rate of early post-transplant AF [20.2 vs. 10.7%, difference: 9.5%, 95% confidence interval (CI): 0.9-18.1%, P = 0.01] and an increased 30 day post-transplant mortality (25.5 vs. 6.4%, hazard ratio: 4.4, 95% CI: 2.6-7.6, P < 0.01), along with a higher percentage of death due to transplant failure (21.2 vs. 4.1%, difference: 17.1%, 95% CI: 8.7-25.5%, P < 0.01). Multivariate analysis revealed a PVR ≥ 300 dyn·s·cm-5 (≥3.75 Wood units) as a significant risk factor for increased 30 day mortality after HTX (hazard ratio: 4.4, 95% CI: 2.5-7.6, P < 0.01). Kaplan-Meier estimator showed a lower 2 year survival after HTX (P < 0.01) in patients with a PVR ≥ 300 dyn·s·cm-5 (≥3.75 Wood units). CONCLUSIONS: Elevated pre-transplant PVR ≥ 300 dyn·s·cm-5 (≥3.75 Wood units) is associated with early post-transplant AF and increased mortality after HTX.

The chameleon of cardiology: cardiac sarcoidosis before and after heart transplantation.

Cardiac sarcoidosis is a chronic inflammatory disease with a large spectrum of symptoms that can mimic diseases such as dilated, hypertrophic, or arrhythmogenic cardiomyopathies. It can be asymptomatic but can also present with ventricular arrhythmias, conduction disease, and heart failure (HF) or even sudden cardiac death (SCD). We present here the case of a patient transplanted due to end-stage arrhythmogenic right ventricular cardiomyopathy (ARVC), fulfilling the task force criteria. A few years after successful heart transplantation (HTX), the patient developed similar symptoms and morphofunctional changes of the heart, which led to critical re-evaluation of his primary diagnosis.

A novel risk score to predict survival in advanced heart failure due to cardiac amyloidosis.

BACKGROUND: Cardiac amyloidosis, caused by deposition of immunoglobulin light chains (AL) or transthyretin (ATTR), carries a poor prognosis. Established risk scores for amyloidosis may not predict outcomes in those patients who develop advanced heart failure and who are potential candidates for heart transplantation. Here, we aimed to identify predictive parameters for patients with severe heart failure due to amyloidosis. METHODS: Out of > 1000 patients with cardiac amyloidosis (AL or ATTR) admitted to our centre between September 1998 and January 2016, a cohort of 120 patients with a complete cardiac assessment at diagnosis, including right heart catheterization, echocardiography and biomarkers, was analysed retrospectively in this study. Primary endpoint was all-cause mortality. We performed univariate and multivariate Cox regression analysis, generated risk scores to predict outcomes in AL and ATTR amyloidosis and compared those to established risk models for amyloidosis. RESULTS: In the Cox multivariate model, high-sensitivity troponin T (hsTnT; hazard ratio (HR) 1.003; confidence interval (CI) 1.001-1.005; p = 0.009) and mean pulmonary artery pressure (HR 1.061; CI 1.024-1.100; p = 0.001) were found to significantly and independently predict outcomes for AL amyloidosis, whereas QRS duration (HR 1.021; CI 1.004-1.039; p = 0.013), hsTnT (HR 1.021; CI 1.006-1.036; p = 0.006) and N-terminal pro-brain natriuretic peptide (HR 1.0003; CI 1.0001-1.0004; p = 0.002) were the best predictors for ATTR amyloidosis. A simple risk score ("HeiRisk") including these parameters for AL and ATTR allowed a more precise risk stratification in our patient population compared to established risk models. CONCLUSIONS: Risk stratification for cardiac amyloidosis with the newly developed "HeiRisk" score may be superior to other staging systems for patients with advanced heart failure due to amyloid cardiomyopathy.

The impact of technical and clinical factors on fecal microbiota transfer outcomes for the treatment of recurrent Clostridioides difficile infections in Germany.

Introduction: Fecal microbiota transfer (FMT) is highly effective in the treatment and prevention of recurrent Clostridioides difficile infection (rCDI) with cure rates of about 80% after a single treatment. Nevertheless, the reasons for failure in the remaining 20% remain largely elusive. The aim of the present study was to investigate different potential clinical predictors of response to FMT in Germany. Methods: Information was extracted from the MicroTrans Registry (NCT02681068), a retrospective observational multicenter study, collecting data from patients undergoing FMT for recurrent or refractory CDI in Germany. We performed binary logistic regression with the following covariates: age, gender, ribotype 027, Eastern Co-operative Oncology Group score, immunosuppression, preparation for FMT by use of proton pump inhibitor, antimotility agents and bowel lavage, previous recurrences, severity of CDI, antibiotic induction treatment, fresh or frozen FMT preparation, and route of application. Results: Treatment response was achieved in 191/240 evaluable cases (79.6%) at day 30 (D30) post FMT and 78.1% at day 90 (D90) post FMT. Assessment of clinical predictors for FMT failure by forward and confirmatory backward-stepwise regression analysis yielded higher age as an independent predictor of FMT failure (p = 0.001; OR 1.060; 95%CI 1.025-1.097). Conclusion: FMT in Germany is associated with high cure rates at D30 and D90. No specific pre-treatment, preparation or application strategy had an impact on FMT success. Only higher age was identified as an independent risk factor for treatment failure. Based on these and external findings, future studies should focus on the assessment of microbiota and microbiota-associated metabolites as factors determining FMT success.

Clinical and genetic insights into non-compaction: a meta-analysis and systematic review on 7598 individuals.

BACKGROUND: Left ventricular non-compaction has been increasingly diagnosed in recent years. However, it is still debated whether non-compaction is a pathological condition or a physiological trait. In this meta-analysis and systematic review, we compare studies, which investigated these two different perspectives. Furthermore, we provide a comprehensive overview on the clinical outcome as well as genetic background of left ventricular non-compaction cardiomyopathy in adult patients. METHODS AND RESULTS: We retrieved PubMed/Medline literatures in English language from 2000 to 19/09/2018 on clinical outcome and genotype of patients with non-compaction. We summarized and extensively reviewed all studies that passed selection criteria and performed a meta-analysis on key phenotypic parameters. Altogether, 35 studies with 2271 non-compaction patients were included in our meta-analysis. The mean age at diagnosis was the mid of their fifth decade. Two-thirds of patients were male. Congenital heart diseases including atrial or ventricular septum defect or Ebstein anomaly were reported in 7% of patients. Twenty-four percent presented with family history of cardiomyopathy. The mean frequency of neuromuscular diseases was 5%. Heart rhythm abnormalities were reported frequently: conduction disease in 26%, supraventricular tachycardia in 17%, and sustained or non-sustained ventricular tachycardia in 18% of patients. Three important outcome measures were reported including systemic thromboembolic events with a mean frequency of 9%, heart transplantation with 4%, and adequate ICD therapy with 15%. Nine studies investigated the genetics of non-compaction cardiomyopathy. The most frequently mutated gene was TTN with a pooled frequency of 11%. The average frequency of MYH7 mutations was 9%, for MYBPC3 mutations 5%, and for CASQ2 and LDB3 3% each. TPM1, MIB1, ACTC1, and LMNA mutations had an average frequency of 2% each. Mutations in PLN, HCN4, TAZ, DTNA, TNNT2, and RBM20 were reported with a frequency of 1% each. We also summarized the results of eight studies investigating the non-compaction in altogether 5327 athletes, pregnant women, patients with sickle cell disease, as well as individuals from population-based cohorts, in which the presence of left ventricular hypertrabeculation ranged from 1.3 to 37%. CONCLUSION: The summarized data indicate that non-compaction may lead to unfavorable outcome in different cardiomyopathy entities. The presence of key features in a multimodal diagnostic approach could distinguish between benign morphological trait and manifest cardiomyopathy.

Pathophysiological background and prognostic implication of systolic aortic root motion in non-ischemic dilated cardiomyopathy.

Recordings of aortic root movement represent one of the first accomplishments of ultrasound in medicine and mark the beginning of functional cardiac imaging. However, the underlying mechanism is not completely understood. Since the aortic root is directly connected to the cardiac skeleton we hypothesize, that the amplitude of systolic aortic root motion (SARM) may be mainly caused by displacement of the cardiac base towards the apex and might therefore be used as measure of left ventricular longitudinal function (LV-LF). One hundred and eighty patients with dilated cardiomyopathy and 180 healthy controls were prospectively included into this study. SARM was lower in patients compared to controls (9 ± 3 mm vs. 12 ± 2 mm, p < 0.001) and lowest in patients with cardiovascular events (9 ± 3 mm vs. 7 ± 3 mm, p < 0.001). During a median follow-up time of 38 months, the combined end-point of cardiovascular death or hospitalization for heart failure was reached by 25 patients (13.9%). Reduced SARM had significant prognostic impact on outcome (hazard ratio 0.74, 95% confidence interval 0.63-0.88, p < 0.001) and remained an independent predictor in the multivariate analysis. Compared to parameters with potential influence on its mechanism, SARM correlated best (r = 0.75, p < 0.001) with global longitudinal strain (GLS). SARM may therefore represent an alternative echocardiographic parameter for the assessment of LV-LF, particularly when GLS is not feasible or apical views are not available.

Implementation of an intensified outpatient follow-up protocol improves outcomes in patients with ventricular assist devices.

BACKGROUND: Ventricular assist devices (VAD) are increasingly used as long-term treatment for advanced heart failure. However, survival after VAD implantation is still unsatisfactory, and no specific outpatient follow-up algorithms have been formally established. Here, we evaluate the effect of an intensified follow-up protocol (IFUP) on survival rates and VAD-associated complications. METHODS AND RESULTS: This is a retrospective study of 57 patients who received a VAD at our center between February 2013 and December 2017. Inclusion criteria were discharge home after VAD implantation and follow-up in our VAD outpatient clinic. Patients implanted after October 2015 (n = 30) were monitored according to IFUP. This protocol embodied formalized, multi-disciplinary clinical visits every 4-8 weeks including a cardiologist, a cardiothoracic surgeon and a VAD-coordinator and was characterized by optimized anticoagulation and wound management as well as guideline-directed medical therapy. One-year survival in the IFUP patients was 97%, compared to 74% in the pre-IFUP era (p = 0.01). Implementation of IFUP was associated with a 90% risk-reduction for 1-year mortality (relative risk 0.099; p = 0.048). The rate of complications, e.g., device thrombosis and major bleeding, was significantly reduced, resulting in superior event-free survival in the IFUP group (p = 0.003). Furthermore, by implementation of IFUP, a more stable anticoagulation adjustment was achieved as well as an improved adherence to guideline-directed medical therapy. CONCLUSION: Implementation of an IFUP for VAD patients is associated with a significant decrease in 1-year all-cause mortality. This emphasizes the need for more vigilance in the management of VAD patients by a dedicated multi-disciplinary team.

Risk factors and survival of patients with permanent pacemaker implantation after heart transplantation.

BACKGROUND: Permanent pacemaker (PPM) implantation after heart transplantation (HTX) may be required due to severe bradycardia. The aim of this study was to investigate the risk factors, indications, perioperative outcomes and complications of PPM implantation after HTX as well as the underlying effect on post-transplant mortality including causes of death. METHODS: This registry study included 621 patients receiving HTX at Heidelberg Heart Center between 1989 and 2018. Patients were stratified by PPM implantation after HTX. Data analysis of risk factors for PPM implantation included donor and recipient demographics, post-transplant medication, mortality, and causes of death. RESULTS: Thirty-six patients (5.8%) received PPM implantation after HTX, 12 (33.3%) with early PPM and 24 (66.7%) with late PPM. Indications for PPM implantation after HTX included sinus node dysfunction (SND) (n=15; 41.7%) and atrioventricular block (AVB) (n=21; 58.3%). Multivariate analysis revealed recipient body mass index (BMI) [hazard ratio (HR): 1.10; confidence interval (CI): 1.01-1.21; P=0.03], donor age (HR: 1.07; CI: 1.03-1.10; P<0.01), and biatrial HTX (HR: 2.63; CI: 1.22-5.68; P=0.01) as significant risk factors for PPM implantation after HTX. Kaplan-Meier estimator displayed a statistically significant inferior 5-year post-transplant survival among patients with early PPM after HTX in comparison to patients with late PPM or no PPM after HTX (P<0.01) along with a higher percentage of death due to infection (P<0.01). CONCLUSIONS: Multivariate risk factors for PPM implantation after HTX include recipient BMI, donor age, and biatrial HTX. Early PPM implantation after HTX is associated with increased 5-year post-transplant mortality due to infection.