A Retrospective Analysis of 10-year Experience on Branched and Fenestrated Endovascular Aortic Arch Repair.

OBJECTIVE: This study aimed to present the early and mid-term outcomes of fenestrated/branched thoracic endovascular aortic repair (f/bTEVAR) for aortic arch pathologies. BACKGROUND: f/bTEVAR represents a less invasive treatment option for aortic arch diseases. Previous published series showed decreased early mortality and morbidity compared to open repair. METHODS: A single-center retrospective analysis of consecutive patients, managed with f/bTEVAR (Cook Medical, Bloomington, IN, USA) between 01.09.11and 30.06.22 was conducted. Primary outcomes were technical success, 30-day mortality and stroke. Data during follow-up and factors affecting early mortality and stroke were analyzed. RESULTS: 209 patients were included (38.3% females; mean age 69.8±3.4years; mean aortic diameter 61±4.7 mm); 14.4% were managed urgently. Fenestrations/scallop configuration was used in 39.7%, branched devices in 55.5% and branch/scallop combination in 4.8%. Landing to zone 0 was performed in 65.5% and in zone 1 in 32.1%. Non-native aortas were used for landing in 39.2%. Technical success was 97.1% and 30-day mortality 9.5%. Strokes were identified in 10%; 5.7% major. Non-native proximal aortic landing zone was an independent protective factor for stroke (P=0.002). Post-operative stroke (P<0.001) and pericardial effusion (P<0.001) were independently related to 30-day mortality. The mean follow-up was 21±8 months. The estimated survival and freedom from reintervention rates were 79.5% (standard error; SE3.1%) and 47.1% (SE 4.3%) at 24months, respectively. CONCLUSIONS: f/bTEVAR presented high technical success and acceptable 30-day mortality. Non-native proximal landing zone was related to lower stroke rate. Half of patients needed a reintervention within the 24-month follow-up.

SARS-CoV-2 Vaccination-Induced Immunogenicity in Heart Transplant Recipients.

Among heart transplant (HT) recipients, a reduced immunological response to SARS-CoV-2 vaccination has been reported. We aimed to assess the humoral and T-cell response to SARS-CoV-2 vaccination in HT recipients to understand determinants of immunogenicity. HT recipients were prospectively enrolled from January 2021 until March 2022. Anti-SARS-CoV-2-Spike IgG levels were quantified after two and three doses of a SARS-CoV-2 vaccine (BNT162b2, mRNA1273, or AZD1222). Spike-specific T-cell responses were assessed using flow cytometry. Ninety-one patients were included in the study (69% male, median age 55 years, median time from HT to first vaccination 6.1 years). Seroconversion rates were 34% after two and 63% after three doses. Older patient age (p = 0.003) and shorter time since HT (p = 0.001) were associated with lower antibody concentrations after three vaccinations. There were no associations between vaccine types or immunosuppressive regimens and humoral response, except for prednisolone, which was predictive of a reduced response after two (p = 0.001), but not after three doses (p = 0.434). A T-cell response was observed in 50% after two and in 74% after three doses. Despite three vaccine doses, a large proportion of HT recipients exhibits a reduced immune response. Additional strategies are desirable to improve vaccine immunogenicity in this vulnerable group of patients.

Hepatitis E virus persists in the ejaculate of chronically infected men.

BACKGROUND & AIMS: Hepatitis E virus (HEV) infections are prevalent worldwide. Various viruses have been detected in the ejaculate and can outlast the duration of viremia, indicating replication beyond the blood-testis barrier. HEV replication in diverse organs, however, is still widely misunderstood. We aimed to determine the occurrence, features and morphology of HEV in the ejaculate. METHODS: The presence of HEV in testis was assessed in 12 experimentally HEV-genotype 3-infected pigs. We further tested ejaculate, urine, stool and blood from 3 chronically HEV genotype 3-infected patients and 6 immunocompetent patients with acute HEV infection by HEV-PCR. Morphology and genomic characterization of HEV particles from various human compartments were determined by HEV-PCR, density gradient measurement, immune-electron microscopy and genomic sequencing. RESULTS: In 2 of the 3 chronically HEV-infected patients, we observed HEV-RNA (genotype 3c) in seminal plasma and semen with viral loads >2 logs higher than in the serum. Genomic sequencing showed significant differences between viral strains in the ejaculate compared to stool. Under ribavirin-treatment, HEV shedding in the ejaculate continued for >9 months following the end of viremia. Density gradient measurement and immune-electron microscopy characterized (enveloped) HEV particles in the ejaculate as intact. CONCLUSIONS: The male reproductive system was shown to be a niche of HEV persistence in chronic HEV infection. Surprisingly, sequence analysis revealed distinct genetic HEV variants in the stool and serum, originating from the liver, compared to variants in the ejaculate originating from the male reproductive system. Enveloped HEV particles in the ejaculate did not morphologically differ from serum-derived HEV particles. LAY SUMMARY: Enveloped hepatitis E virus particles could be identified by PCR and electron microscopy in the ejaculate of immunosuppressed chronically infected patients, but not in immunocompetent experimentally infected pigs or in patients with acute self-limiting hepatitis E.

Next-generation sequencing of 32 genes associated with hereditary aortopathies and related disorders of connective tissue in a cohort of 199 patients.

PURPOSE: Heritable factors play an important etiologic role in connective tissue disorders (CTD) with vascular involvement, and a genetic diagnosis is getting increasingly important for gene-tailored, personalized patient management. METHODS: We analyzed 32 disease-associated genes by using targeted next-generation sequencing and exome sequencing in a clinically relevant cohort of 199 individuals. We classified and refined sequence variants according to their likelihood for pathogenicity. RESULTS: We identified 1 pathogenic variant (PV; in FBN1 or SMAD3) in 15 patients (7.5%) and ≥1 likely pathogenic variant (LPV; in COL3A1, FBN1, FBN2, LOX, MYH11, SMAD3, TGFBR1, or TGFBR2) in 19 individuals (9.6%), together resulting in 17.1% diagnostic yield. Thirteen PV/LPV were novel. Of PV/LPV-negative patients 47 (23.6%) showed ≥1 variant of uncertain significance (VUS). Twenty-five patients had concomitant variants. In-depth evaluation of reported/calculated variant classes resulted in reclassification of 19.8% of variants. CONCLUSION: Variant classification and refinement are essential for shaping mutational spectra of disease genes, thereby improving clinical sensitivity. Obligate stringent multigene analysis is a powerful tool for identifying genetic causes of clinically related CTDs. Nonetheless, the relatively high rate of PV/LPV/VUS-negative patients underscores the existence of yet unknown disease loci and/or oligogenic/polygenic inheritance.

Sex differences in preformed panel-reactive antibody levels and outcomes in patients undergoing heart transplantation.

BACKGROUND: Sex differences in panel-reactive antibody (PRA) levels in heart transplant recipients and their association with transplant-related outcomes are mostly unknown. METHODS: In 20 181 (24.7% women) first-time heart transplant recipients included from July 2004 to March 2015 in the prospective Organ Procurement and Transplantation Network (OPTN), we studied sex differences in most recent (mr) and peak (p)PRA and outcomes (graft failure, rejection, cardiac allograft vasculopathy [CAV], retransplantation, and mortality). Median follow-up (all-cause mortality) was 6 years. Analyses are based on OPTN data (March 6, 2017). RESULTS: MrPRA levels were associated with all-cause mortality (hazard ratio, 95% confidence interval: class I 1.03, 1.01-1.04, P < 0.001) and acute rejection (class II 1.08, 1.03-1.14, P = 0.0044). PPRA levels were associated with all-cause mortality (class I 1.02, 1.00-1.04, P = 0.015) and CAV (class II 1.03, 1.01-1.06, P = 0.020). Sex interactions were seen for the association of pPRA and graft failure with a higher risk in women, and for pPRA and CAV with a higher risk in men. CONCLUSIONS: PRA were associated with different transplant-related outcomes in both sexes. However, women with elevated pPRA were shown to be at higher risk for graft failure, whereas higher levels of pPRA were more hazardous for men in developing CAV.

HEV-positive blood donations represent a relevant infection risk for immunosuppressed recipients.

BACKGROUND & AIMS: Routine HEV testing of blood products has recently been implemented in Great Britain and the Netherlands. The relevance of transfusion-transmitted HEV infections is still controversially discussed in Europe. METHODS: All blood donations at the University Medical Center Hamburg-Eppendorf were prospectively tested for HEV RNA by pooled PCR from October 2016 to May 2017. Reactive samples were individually retested. Additionally, stored samples from previous donations of positive donors were tested to determine the duration of HEV viraemia. HEV RNA-positive donors and a control cohort were asked to answer a questionnaire. RESULTS: Twenty-three out of 18,737 HEV RNA-positive donors were identified (0.12%). Only two of the positive donors (8.7%) presented with elevated aminotransferases at time of donation (alanine aminotransferase: 192 and 101 U/L). The retrospective analysis of all positive donors revealed that four asymptomatic donors had been HEV viraemic for up to three months with the longest duration of HEV viraemia exceeding four months. Despite the HEV-testing efforts, 14 HEV RNA-positive blood products were transfused into 12 immunocompromised and two immunocompetent patients. One recipient of these products developed fatal acute-on-chronic liver failure complicated by Pseudomonas septicemia. The questionnaire revealed that HEV RNA-positive donors significantly more often consumed raw pork meat (12 out of 18; 67%) than controls (89 out of 256; 35%; p = 0.01). In two donors, undercooked pork liver dishes were identified as the source of infection. HEV genotyping was possible in 7 out of 23 of HEV viraemic donors and six out of seven isolates belonged to HEV Genotype 3, Group 2. CONCLUSIONS: Prolonged HEV viraemia can be detected at a relatively high rate in Northern German blood donors, leading to transfusion-transmitted HEV infections in several patients with the risk of severe and fatal complications. Eating raw pork tartare represented a relevant risk for the acquisition of HEV infection. LAY SUMMARY: The relevance of transfusion-transmitted hepatitis E virus infections has been discussed controversially. Herein, we present the first report on routine hepatitis E virus screening of blood donations at a tertiary care centre in Germany. Hepatitis E viraemia was found at a relatively high rate of 0.12% among blood donors, which represents a relevant transfusion-related risk for vulnerable patient populations.

Non-contrast MR angiography at 1.5 Tesla for aortic monitoring in Marfan patients after aortic root surgery.

BACKGROUND: Contrast-enhanced cardiovascular magnetic resonance angiography (CE-CMRA) is the established imaging modality for patients with Marfan syndrome requiring life-long annual aortic imaging before and after aortic root replacement. Contrast-free CMRA techniques avoiding side-effects of contrast media are highly desirable for serial imaging but have not been evaluated in the postoperative setup of Marfan patients. The purpose of this study was to assess the feasibility of non-contrast balanced steady-state free precession (bSSFP) magnetic resonance imaging for aortic monitoring of postoperative patients with Marfan syndrome. METHODS: Sixty-four adult Marfan patients after aortic root replacement were prospectively included. Fourteen patients (22%) had a residual aortic dissection after surgical treatment of type A dissection. bSSFP imaging and CE-CMRA were performed at 1.5 Tesla. Two radiologists evaluated the images regarding image quality (1 = poor, 4 = excellent), artifacts (1 = severe, 4 = none) and aortic pathologies. Readers measured the aortic diameters at defined levels in both techniques. Statistics included observer agreement for image scoring and diameter measurements and ROC analyses for comparison of the diagnostic performance of bSSFP and CE-CMRA. RESULTS: Both readers observed no significant differences in image quality between bSSFP and CE-CMRA and found a median image quality score of 4 for both techniques (all p > .05). No significant differences were found regarding the frequency of image artifacts in both sequences (all p > .05). Sensitivity and specificity for detection of aortic dissections was 100% for both readers and techniques. Compared to bSSFP imaging, CE-CMRA resulted in higher diameters (mean bias, 0.9 mm; p < .05). The inter-observer biases of diameter measurements were not significantly different (all p > .05), except for the distal graft anastomosis (p = .001). Using both techniques, the readers correctly identified a graft suture dehiscence with aneurysm formation requiring surgery. CONCLUSION: Unenhanced bSSFP CMR imaging allows for riskless aortic monitoring with high diagnostic accuracy in Marfan patients after aortic root surgery.

Results of modern mitral valve repair in patients with Marfan syndrome.

OBJECTIVES: Mitral valve (MV) regurgitation is a common manifestation in patients with Marfan syndrome (MFS) and is age dependent. Valve pathology shares some features with myxomatous MV disease. Surgical treatment is still being debated and not well characterized in patients with MFS. PATIENTS AND METHODS: We retrospectively evaluated the results of mitral valve repair (MVR) of symptomatic patients with MFS who underwent surgery between January 2004 and April 2011. MFS was diagnosed following the Ghent criteria. MVR was performed in 12 patients. Three patients underwent minimally invasive MVR despite severe thorax deformities. Mean follow-up was 60.1 months (95% CI: 48-72) and was complete. RESULTS: Thirty-day mortality was 0%. One patient died because of arrhythmia 66 months after MVR. Transthoracic echocardiography at last visit showed mild mitral regurgitation in one patient (8.3%) and no mitral regurgitation in the remaining patients (91.7%). CONCLUSION: MVR was associated with excellent survival and a low rate of complications. Transthoracic echocardiography showed good results of the repaired valves even years later. Minimally invasive repairs are feasible even in deformed thoraces, lowering the risk for future aortic surgery. Because of excellent mid-term to long-term results, MVR may also be justified in asymptomatic Marfan patients.

Impact of age and gender on cardiac pathology in children and adolescents with Marfan syndrome.

Cardiac pathologies are the major aspect in the treatment strategies for Marfan syndrome (MFS). In this progressive disease, less is known about manifestations and progression of cardiovascular symptoms in children. To define a certain decision regarding therapeutic options, knowledge concerning the onset of cardiovascular findings is essential. From 1998 to 2011, suspected pediatric Marfan patients were subjected to a standardized diagnostic program. Cardiovascular findings were analyzed in terms of age at first clinical manifestation, prevalence and gender differences, morbidity, mortality, and treatment. Marfan syndrome was diagnosed in 82 patients (46 boys; mean age at diagnosis, 9.0 ± 5.7 years). At first presentation, aortic root dilation was found in 56 % of patients, mitral valve prolapse in 31 %, whereas pulmonary artery dilation was detected in 22 % and tricuspid valve prolapse in only 17 % of patients. Aortic (2.5 %) and mitral valve regurgitations (22 %) are significantly correlated with aortic root dilation (p < 0.01) and mitral valve prolapse (p < 0.05) but without relevant progression during childhood. Prophylactic medication was initiated for 42 % of the patients (mean age, 8.0 ± 4.5 years) because of progressive aortic root dilation. Aortic dissection did not appear. Aortic root surgery was needed for 4 % of the patients. Gender-specific differences in cardiovascular findings, progression of disease, or treatment did not appear. Comparable with adults, aortic root dilation is the most frequent cardiovascular finding in children and associated with relevant morbidity, whereas aortic and mitral valve regurgitation are of minor clinical relevance. Manifestation at an early age and slow progression of cardiovascular findings underscore the necessity of repeated echocardiographic examinations for early diagnosis and start of prophylactic treatment.

Physical and Mental Recovery after Aortic Valve Surgery in Non-Elderly Patients: Native Valve-Preserving Surgery vs. Prosthetic Valve Replacement.

Background: Exercise capacity and patient-reported outcomes are increasingly considered crucial following aortic valve (AV) surgery in non-elderly adults. We aimed to prospectively evaluate the effect of native valve preservation compared with prosthetic valve replacement. Methods: From October 2017 to August 2020, 100 consecutive non-elderly patients undergoing surgery for severe AV disease were included. Exercise capacity and patient-reported outcomes were evaluated upon admission, and 3 months and 1 year postoperatively. Results: In total, 72 patients underwent native valve-preserving procedures (AV repair or Ross procedure, NV group), and 28 patients, prosthetic valve replacement (PV group). Native valve preservation was associated with an increased risk of reoperation (weighted hazard ratio: 10.57 (95% CI: 1.24-90.01), p = 0.031). The estimated average treatment effect on six-minute walking distance in NV patients at 1 year was positive, but not significant (35.64 m; 95% CI: -17.03-88.30, adj. p = 0.554). The postoperative physical and mental quality of life was comparable in both groups. Peak oxygen consumption and work rate were better at all assessment time points in NV patients. Marked longitudinal improvements in walking distance (NV, +47 m (adj. p < 0.001); PV, +25 m (adj. p = 0.004)) and physical (NV, +7 points (adj. p = 0.023); PV, +10 points (adj. p = 0.005)) and mental quality of life (NV, +7 points (adj. p < 0.001); PV, +5 points (adj. p = 0.058)) from the preoperative period to the 1-year follow-up were observed. At 1 year, there was a tendency of more NV patients reaching reference values of walking distance. Conclusions: Despite the increased risk of reoperation, physical and mental performance markedly improved after native valve-preserving surgery and was comparable to that after prosthetic aortic valve replacement.

Heart Rate Reduction and Outcomes in Heart Failure Outpatients.

Aim. Pharmacologic reduction in heart rate with beta-blockers (BB) or ivabradine is associated with improved survival in heart failure (HF) with sinus rhythm. We analyzed the association of different heart rate-reducing drug treatments on outcomes in HF outpatients. Methods. Consecutive patients with HF in sinus rhythm referred to a specialized tertiary service were prospectively enrolled from August 2015 until March 2018. Clinical characteristics were assessed at baseline. We performed Cox regression analyses to examine the effect of the resting heart rate and different heart rate-reducing drug regimens on all-cause mortality and a composite endpoint of "all-cause mortality or heart transplantation" over a mean follow-up of 3.1 years. Results. Of the 278 patients included, 213 (76.6%) were male, the median age was 57.0 years (IQR 49.0-66.1), and 185 (73.7%) had an ejection fraction <40%. Most patients received BB in submaximal [n = 118] or maximum dose [n = 136]. Patients on BB in maximum dose plus ivabradine [n = 24] were younger (53.0 vs. 58.0 years) and had a lower EF (25 vs. 31%). Higher resting heart rate was associated with an increased risk of death or transplantation (HR 1.03 [1.01, 1.06], p = 0.0072), even after adjusting for age and sex. There were no differences between the groups concerning all-cause mortality or the composite endpoint. Conclusion. Our prospective study confirms the association between low heart rate and survival in HF patients receiving various heart rate-reducing medications. We could not identify a specific effect of either regimen.

Supervised exercise training in patients with advanced heart failure and left ventricular assist device: A multicentre randomized controlled trial (Ex-VAD trial).

AIMS: Small studies and observations suggested that exercise training may improve peak oxygen consumption (peakVO2 ) in patients with advanced heart failure and left ventricular assist device (LVAD). We investigated whether in this patient group a supervised exercise training can improve exercise capacity. METHODS AND RESULTS: In this multicentre, prospective, randomized, controlled trial, patients with stable heart failure and LVAD were randomly assigned (2:1) to 12 weeks of supervised exercise training or usual care, with 12 weeks of follow-up. The primary endpoint was the change in peakVO2 after 12 weeks (51 patients provided a power of 90% with an expected group difference in peakVO2 of 3 ml/kg/min). Secondary endpoints included changes in submaximal exercise capacity and quality of life. Among 64 patients enrolled (97% male, mean age 56 years), 54 were included in the analysis. Mean difference in the change of peakVO2 after 12 weeks was 0.826 ml/min/kg (95% confidence interval [CI] -0.37, 2.03; p = 0.183). There was a positive effect of exercise training on 6-min walk distance with a mean increase in the intervention group by 43.4 m (95% CI 16.9, 69.9; p = 0.0024), and on the Kansas City Cardiomyopathy Questionnaire physical domain score (mean 14.3, 95% CI 3.7, 24.9; p = 0.0124), both after 12 weeks. The overall adherence was high (71%), and there were no differences in adverse events between groups. CONCLUSION: In patients with advanced heart failure and LVAD, 12 weeks of exercise training did not improve peakVO2 but demonstrated positive effects on submaximal exercise capacity and physical quality of life.

Concomitant cardiovascular malformations in isolated bicuspid aortic valve disease: a retrospective cross-sectional study and meta-analysis.

Background: Congenital bicuspid aortic valve affects up to 2% of the general population. It occurs in complex congenital heart defects or in syndromes such as Turner, Marfan, or Loeys-Dietz. However, the majority of bicuspid aortic valves are considered to manifest as isolated malformations. Methods: We aimed to assess retrospectively associated cardiovascular malformations in 200 individuals with bicuspid aortic valve considered to occur as an isolated manifestation. All individuals underwent transthoracic echocardiography, 164 thoracoabdominal tomographic imaging, and 84 coronary artery imaging. In addition, we also performed a meta-analysis of data from the literature to assess the occurrence of associate malformations. Results: In our retrospective cross-sectional study collective, the mean age was 45±15 years, 154 (77%) individuals were male. Anatomy of bicuspid aortic valve according to Schaefer was type 1 in 142 (71%), type 2 in 35 (18%), type 3 in 2 (1%), unicuspid in 6 (3%), and unclassified in 15 (8%) individuals. Coarctation of the aorta had 4.2% of individuals, 3.6% had coronary anomalies. No individual had a patent ductus arteriosus, 0.5% had atrial and ventricular septal defect each, 1.5% mitral valve prolapse. No individual had a tricuspid valve prolapse. Our meta-analysis identified in cohorts with isolated bicuspid aortic valve 11.8% (95% CI: 7.7-16.0%) individuals with aortic coarctation, 3.7% (95% CI: 1.2-6.1%) with coronary anomalies, 3.3% (95% CI: 0.0-6.7%) with patent ductus arteriosus, 5.9% (95% CI: 1.3-10.5%) with ventricular septal defect and 1.6% (95% CI: 1.1-2.1%) with mitral valve prolapse. Conclusions: Individuals with isolated bicuspid aortic valve may exhibit a variety of associated cardiovascular malformations and therefore screening for associated malformations may be warranted.

Sleep apnea predicts cardiovascular death in patients with Marfan syndrome: a cohort study.

Background: Surgical replacement of the aortic root is the only intervention that can prevent aortic dissection and cardiovascular death in Marfan syndrome (MFS). However, in some individuals, MFS also causes sleep apnea. If sleep apnea predicts cardiovascular death, a new target for predictive, preventive, and personalized medicine (PPPM) may emerge for those individuals with MFS who have sleep apnea. Methods: This is an investigator-initiated study with long-term follow-up data of 105 individuals with MFS. All individuals were screened for sleep apnea regardless of symptoms. Cardiovascular death served as a primary endpoint, and aortic events as a secondary outcome. Results: Sleep apnea with an apnea-hypopnea index (AHI) > 5/h was observed in 21.0% (22/105) with mild sleep apnea in 13% (14/105) and moderate to severe sleep apnea in 7.6% (8/105). After a median follow-up of 7.76 years (interquartile range: 6.84, 8.41), 10% (10/105) had died, with cardiovascular cause of death in 80% (8/10). After adjusting for age and body mass index (BMI), the AHI score emerged as an independent risk factor for cardiovascular death (hazard ratio 1.712, 95% confidence interval [1.061-2.761], p = 0.0276). The secondary outcome of aortic events occurred in 33% (35/105). There was no effect of the AHI score on aortic events after adjusting for age and BMI (hazard ratio 0.965, 95% confidence interval [0.617-1.509]), possibly due to a high number of patients with prior aortic surgery. Interpretation: Sleep apnea is emerging as an independent predictor of cardiovascular death in MFS. It seems mandatory to screen all individuals with MFS for sleep apnea and to include these individuals, with both MFS and sleep apnea, in further studies to evaluate the impact of preventive measures with regard to cardiovascular death. Supplementary Information: The online version contains supplementary material available at 10.1007/s13167-022-00291-4.

Gender differences in characteristics and outcomes in heart failure patients referred for end-stage treatment.

AIMS: Despite signals from clinical trials and mechanistic studies implying different resilience to heart failure (HF) depending on gender, the impact of gender on presentation and outcomes in patients with HF remains unclear. This study assessed the impact of gender on clinical presentation and outcomes in patients with HF referred to a specialised tertiary HF service. METHODS AND RESULTS: Consecutive patients with HF referred to a specialised tertiary HF service offering advanced therapy options including left ventricular assist devices (LVAD) and heart transplantation were prospectively enrolled from August 2015 until March 2018. We assessed clinical characteristics at baseline and performed survival analyses and age-adjusted Cox regression analyses in men vs. women for all-cause death and a combined disease-related endpoint comprising death, heart transplantation, and LVAD implantation. Analyses were performed for the overall study population and for patients with HF with reduced ejection fraction (HFrEF). Of 356 patients included, 283 (79.5%) were male. The median age was 58 years (interquartile range 50-67). Two hundred and fifty-one (74.5%) patients had HFrEF. HF aetiology, ejection fraction, functional status measures, and most of the cardiac and non-cardiac comorbidities did not differ between men and women. In a median follow-up of 3.2 years, 50 patients died (45 men, 5 women), 15 patients underwent LVAD implantation, and 8 patients heart transplantation. While all-cause death was not significantly different between both genders in the overall population [16.9 vs. 6.0%, P = 0.065, hazard ratio (HR) 2.29 (95% confidence interval 0.91-5.78), P = 0.078], in the HFrEF subgroup, a significant difference between men and women was observed [20.7% vs. 3.9%, P = 0.017, HR 3.67 (95% confidence interval 1.13-11.91), P = 0.031]. The combined endpoint was more often reached in men than in women in both the overall population [21.6% vs. 9.0%, P = 0.053, HR 2.51 (1.08-5.82), P = 0.032] and the HFrEF subgroup [27.1% vs. 7.7%, P = 0.015, HR 3.58 (1.29-9.94), P = 0.014]. CONCLUSIONS: Patients referred to a specialised tertiary HF service showed a similar clinical profile without relevant gender differences. In the mid-term follow-up, more male than female patients died or underwent heart transplantation and LVAD implantation. These findings call for independent validation and for further research into gender-specific drivers of HF progression.

Left Ventricular Assist Device Implantation and Concomitant Dor Procedure: a Single Center Experience.

OBJECTIVE: Left ventricular assist device (LVAD) implantation with concomitant Dor plasty is only reported anecdotally. We herein aimed to describe our experience with LVAD and concomitant Dor procedures and describe long-term outcomes of this special subset of heart failure patients. METHODS: Between January/2010 and December/2018, 144 patients received LVAD therapy at our institution. Of those, five patients (80% male, 60.4±7.2 years) presented with an apical aneurysm and received concomitant Dor plasty. Apical aneurysms presented diameter between 75 and 98 mm, with one impending rupture. RESULTS: Procedural success was achieved in all patients. No unplanned right ventricular assist device implantation occurred. Furthermore, no acute 30-day mortality was seen. In follow-up, one patient was lost due to intentional disconnection of the driveline. One patient underwent heart transplantation on postoperative day 630. The remaining three patients are still on device with sufficient flow; pump thromboses were successfully managed by lysis therapy in one patient. CONCLUSION: LVAD implantation with concomitant Dor procedure is feasible, safe, and occasionally performed in patients with ischemic cardiomyopathy. Major advantages are prevention of thromboembolism and facilitation of LVAD placement by improving pump stability and warranting midventricular, coaxial alignment of the inflow cannula. In long-term follow-up, no adverse event associated with Dor plasty was observed.

Assessing palliative care need in left ventricular assist device patients and heart transplant recipients.

OBJECTIVES: Palliative care (PC) has gained rising attention in a holistic treatment approach to chronic heart failure (HF). It is unclear whether there is a need for PC in left ventricular assist device (LVAD) patients or heart transplant recipients. METHODS: In a cross-sectional explorative pilot study, outpatients after heart transplantation (HTx, n = 69) or LVAD implantation (n = 21) underwent screening for palliative care (PC) need and evaluation of symptom burden and psychological distress using tools that emanated from palliative cancer care. RESULTS: The 'Palliative Care Screening Tool for Heart Failure Patients' revealed scores of 4.3 ± 2.2 in HTx and 6.0 ± 2.1 in LVAD patients (max. 12 points, P = 0.003), indicating the need for PC (≥5 points) in 32% of HTx and 67% of LVAD patients. Symptom burden, as assessed by MIDOS ('Minimal Documentation System for Palliative Care') scores was substantial in both groups (4.9 ± 4.7 in HTx vs 6.6 ± 5.3 in LVAD, max. 30 points, P = 0.181). 'Fatigue', 'weakness' and 'pain' were the most frequent symptoms. Using the 'Distress-Thermometer', 'clinically relevant' distress was detected in 57% of HTx and 47% of LVAD patients (P = 0.445). In the PHQ-4 ('4-Item Patient Health Questionnaire'), 45% of LVAD patients, compared to only 10% of HTx patients, reported mild symptoms of anxiety and depression. CONCLUSIONS: Findings reveal substantial need for PC in LVAD patients and, to a lesser extent, in heart transplant recipients, suggesting that multi-disciplinary PC should be introduced into routine aftercare.

Marfan Syndrome Versus Bicuspid Aortic Valve Disease: Comparative Analysis of Obstetric Outcome and Pregnancy-Associated Immediate and Long-Term Aortic Complications.

Pregnancy poses a threat to women with aortopathy. Conclusive data on the obstetric and aortic outcome in this risk collective, especially when it comes to aortic complications in the long term, are still missing. This study offers a comparative analysis of pregnancy-associated outcome in 113 consecutive women with Marfan syndrome or bicuspid aortic valve disease, including 46 ever-pregnant and 37 never-pregnant women with Marfan syndrome, and 23 ever-pregnant and 7 never-pregnant females with bicuspid aortic valve disease. The overall obstetric outcome was comparable between ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease (p = 0.112). Pregnancy-associated aortic dissection occurred in two women with Marfan syndrome (3%) during a total of 62 completed pregnancies, whereas no single case of aortic event occurred in women with bicuspid aortic valve disease during a total of 36 completed pregnancies (p = 0.530). In the long-term follow-up, aortic dissection occurred in 21% of ever-pregnant women with Marfan syndrome, but in none of the women with bicuspid aortic valve disease (p = 0.022). Proximal aortic surgery was performed with similar frequency in ever-pregnant women with Marfan syndrome and with bicuspid aortic valve disease in the long term (p = 0.252). However, ever-pregnant women with Marfan syndrome were younger when surgery was performed (44 ± 9 vs. 59 ± 7 years; p = 0.041). In Marfan syndrome, long-term growth of the aorta was comparable between ever-pregnant and never-pregnant women. Pregnancy thus exhibited an increased immediate aortic risk only in women with Marfan syndrome, but not in women with bicuspid aortic valve disease. Previous pregnancy did not relate to an increased long-term risk of adverse aortic events in women with Marfan syndrome or with bicuspid aortic valve disease.

The spectrum of syndromes and manifestations in individuals screened for suspected Marfan syndrome.

The diagnosis of Marfan syndrome (MFS) is based on evaluating a large number of clinical criteria. We have observed that many persons presenting in specialized centers for "Marfan-like" features do not have MFS, but exhibit a large spectrum of other syndromes. The spectrum of these syndromes and the distribution of "Marfan-like" features remain to be characterized. Thus, we prospectively evaluated 279 consecutive patients with suspected MFS (144 men and 135 women at a mean age of 34+/-13 years) for presence of 27 clinical criteria considered characteristic of MFS. The most frequent reasons to refer individuals for suspected MFS were skeletal features (31%), a family history of MFS, or aortic complications (29%), aortic dissection or aneurysm (19%), and eye manifestations (9%). Using established criteria, we confirmed MFS in 138 individuals (group 1) and diagnosed other connective tissue diseases, both with vascular involvement in 30 (group 2) and without vascular involvement in 39 (group 3), and excluded any distinct disease in 72 individuals (group 4). Clinical manifestations of MFS were present in all four patient groups and there was no single clinical criterion that exhibited positive and negative likelihood ratios that were per se sufficient to confirm or rule out MFS. We conclude that "Marfan-like" features are not exclusively indicative of MFS but also of numerous, alternative inherited diseases with many of them carrying a hitherto poorly defined cardiovascular risk. These alternative diseases require future study to characterize their responses to therapy and long-term prognosis.