Cardio-Hepatic Interaction in Cardiac Amyloidosis.

Background: Congestion is associated with poor prognosis in cardiac amyloidosis (CA). The cardio-hepatic interaction and the prognostic impact of secondary liver affection by cardiac congestion in CA are poorly understood and require further characterisation. Methods: Participants of the amyloidosis cohort study AmyKoS at the Interdisciplinary Amyloidosis Centre of Northern Bavaria with proven transthyretin (ATTR-CA) and light chain CA (AL-CA) underwent serial work-up including laboratory tests, echocardiography, and in-depth hepatic assessment by vibration-controlled transient elastography (VCTE) and 13C-methacetin breath test. Results: In total, 74 patients with AL-CA (n = 17), ATTR-CA (n = 26) and the controls (n = 31) were analysed. ATTR-CA patients showed decreased microsomal liver function expressed by maximal percentage of dose rate (PDRpeak) related to hepatic congestion. Reduced PDRpeak in AL-CA could result from altered pharmacokinetics due to changed hepatic blood flow. Liver stiffness as a combined surrogate of chronic liver damage and congestion was identified as a predictor of all-cause mortality. Statistical modelling of the cardio-hepatic interaction revealed septum thickness, NT-proBNP and PDRpeak as predictors of liver stiffness in both CA subtypes; dilatation of liver veins and the fibrosis score FIB-4 were only significant for ATTR-CA. Conclusions: Non-invasive methods allow us to characterise CA-associated hepatic pathophysiology. Liver stiffness might be promising for risk stratification in CA.

First clinical experience with the novel cold storage SherpaPak™ system for donor heart transportation.

BACKGROUND: The current gold standard for donor heart preservation is a three-bag-technique and storage in a cooler filled with slush ice. This technique can cause freezing injury with protein denaturation. We report our early experience with a single-use disposable device (SherpaPak™, Paragonix Technologies, MA, USA) specifically designed for sterile permanent temperature-controlled transportation of donor hearts. METHODS: In this case control study with 2:1 matching we identified 21 patients after heart transplantation depending on type of organ transport (standard three-bag-technique vs. SherpaPak™). The outcome after donor heart storage in the SherpaPak™ was compared with donor heart transportation with the standard technique. RESULTS: Since July 2018 seven patients (5 males; mean age 50.3±13.2years) underwent heart transplantation with the SherpaPak™ system. Cold ischemic time was longer in the SherpaPak™ group (207.7±23.3 vs. 181.6±21.9, P=0.027). SherpaPak™ kept the organ temperature at 5.1±0.8 °C, with an average outside temperature of 21.4±3.6 °C. Among all 21 transplanted patients four developed fatal early graft failure (28.6% vs. 21.4%, P=0.432). Over the first hours we noticed no difference in hemodynamic parameters, CK-MB levels or vasoactive-inotropic score. During first follow-up we noticed slightly better right heart function in the SherpaPak™ group (TAPSE 17.83±2.71 vs. 14.52±2.61 mm, P=0.020). We identified no positive blood cultures in the SherpaPak™ group within the first 30 days after heart transplantation. CONCLUSIONS: The SherpaPak™ provides a constant temperature during transportation with permanent monitoring, never dropping below 4 °C. Organs transported with this novel device showed a normal perioperative function.

Secondary sclerosing cholangitis in cardiac surgical patients: A complication with a dismal prognosis.

OBJECTIVES: Secondary sclerosing cholangitis in critically ill patients is a rapidly progressing disease leading to biliary fibrosis and cirrhosis. We describe the course of sclerosing cholangitis in critically ill patients after cardiac surgery and compare this with matched patients. METHODS: A retrospective search for "secondary sclerosing cholangitis" and "liver and/or hepatic failure" in all adult patients (aged 18-93 years) who underwent cardiac surgery from April 2007 to March 2016 identified 192 of 8625 patients. Of those, 12 were diagnosed with sclerosing cholangitis in critically ill patients (incidence, 0.14%). A 3:1 matching was performed. Laboratory values, pharmacologic requirements, ventilation times, mechanical circulatory support, and endoscopic retrograde cholangiopancreatography studies were extracted from the hospital database. RESULTS: A total of 9 men and 3 women were affected (age 71 years; range, 59.8-75.5 years). Critically ill patients with sclerosing cholangitis required vasoconstrictors and inotropes longer than control patients (norepinephrine 356.5 hours [264.5-621] vs 68 hours [15-132.5], P = .003; enoximone 177 hours [124.3-249.5] vs 48.5 hours [12-81 hours], P < .001, respectively). Critically ill patients with sclerosing cholangitis had longer intubation time (628.5 hours [377.3-883] vs 25 hours [9.8-117.5]; P < .001) and more surgical revisions (3 [2.5-6] vs 1 [0-2], P = .003) than the matching group. Bilirubin (23.3 mg/dL [14.4-32.9] vs 1 mg/dL [0.6-2.7]; P < .001), gamma-glutamyltransferase (1082.3 U/L [259.5-2265.7] vs 53.8 U/L [35.1-146]; P < .001), and alkaline phosphatase (751.5 U/L [372-1722.3] vs 80.5 U/L [53.3-122]; P < .001) were higher in critically ill patients with sclerosing cholangitis. One critically ill patient with sclerosing cholangitis underwent successful liver transplantation. A total of 11 patients sclerosing cholangitis died (92%) versus 12 patients (33%, P < .001) in the control group. CONCLUSIONS: Sclerosing cholangitis in critically ill patients is a fatal complication in patients undergoing cardiac surgery who have a complicated postoperative course with prolonged vasoconstrictor, inotropic, and respiratory therapy, or who require frequent surgical revisions. Liver transplantation remains the only curative option but is often precluded by the age and critical state of patients undergoing cardiac surgery.

Rapid deployment valve system shortens operative times for aortic valve replacement through right anterior minithoracotomy.

BACKGROUND: There is growing evidence from the literature that right anterior minithoracotomy aortic valve replacement (RAT-AVR) improves clinical outcome. However, increased cross clamp time is the strongest argument for surgeons not performing RAT-AVR. Rapid deployment aortic valve systems have the potential to decrease cross-clamp time and ease this procedure. We assessed clinical outcome of rapid deployment and conventional valves through RAT. METHODS: Sixty-eight patients (mean age 76 ± 6 years, 32% females) underwent RAT-AVR between 9/2013 and 7/2015. According to the valve type implanted the patients were divided into two groups. In 43 patients (R-group; mean age 74.1 ± 6.6 years) a rapid deployment valve system (Edwards Intuity, Edwards Lifesciences Corp; Irvine, Calif) and in 25 patients (C-group; mean age 74.2 ± 6.6 years) a conventional stented biological aortic valve was implanted. RESULTS: Aortic cross-clamp (42.1 ± 12 min vs. 68.3 ± 20.3 min; p < 0.001) and bypass time (80.4 ± 39.3 min vs. 106.6 ± 23.2 min; p = 0.001) were shorter in the rapid deployment group (R-group). We observed no differences in clinical outcome. Postoperative gradients (R-group: max gradient, 14.3 ± 8 mmHg vs. 15.5 ± 5 mmHg (C-group), mean gradient, 9.2 ± 1.7 mmHg (R-group) vs. 9.1 ± 2.3 mmHg (C-group) revealed no differences. However, larger prostheses were implanted in C-group (25 mm; IQR 23-27 mm vs. 23 mm; IQR 21-25; p = 0.009). CONCLUSIONS: Our data suggest that the rapid deployment aortic valve system reduced cross clamp and bypass time in patients undergoing RAT-AVR with similar hemodynamics as with larger size stented prosthesis. However, larger studies and long-term follow-up are mandatory to confirm our findings.

Benefit of phosphodiesterase 4 inhibitors as supplemental therapy after lung transplantation concerning their antiproliferative effects: an experimental study using a heterotopic rodent model.

BACKGROUND: Recent advances in the understanding of immunomodulatory properties of phosphodiesterase 4 (PDE4) inhibitors recommend these drugs for immunosuppressive therapy after lung transplantation. The potency of three PDE4 inhibitors was tested using an established model of heterotopic tracheal transplantation in rats. METHODS: Five allogenic groups were investigated and treated with the PDE4 inhibitors: rolipram, cilomilast (Ariflo, SB-207499, SmithKline Beecham, Munich, Germany), roflumilast (Altana Pharmacia, Bad Homburg, Germany) or cyclosporine A (CsA), or left without immunosuppression. The grafts were quantitatively analyzed for epithelial integrity, monocyte/macrophage content, cell proliferation, and tracheal obliteration by histology/immunohistochemistry (days 1, 5, 7, 21, 28; n=4-7). RESULTS: In animals treated with the PDE4 inhibitors, the epithelium was completely lost until day 21. The epithelium was partially preserved in the rats receiving CsA until day 28. In the acute phase (days 5 and 7) the infiltration of monocytes and macrophages was significantly inhibited similarly (cilomilast) or less effective (rolipram, roflumilast) as in CsA-treated rats. In the chronic phase (day 28) the significant increase of monocytes and macrophages after CsA-treatment was not found in PDE4 inhibitor-treated rats. The PDE4 inhibitors showed lower (rolipram) or higher (cilomilast, roflumilast) potency as CsA to inhibit the cell proliferation. Only treatment with PDE4 inhibitor (Ariflo) significantly inhibited the obliteration, but to a lesser degree as CsA. CONCLUSION: The PDE4 inhibitors tested in our study are not suitable on their own for immunosuppressive therapy after lung transplantation because of the limited protection against the epithelial disturbance, infiltration of immune cells, and luminal obliteration. The strong anti-proliferative effect of the second-generation PDE4 inhibitors, cilomilast and roflumilast, suggest a benefit for the effective inhibition of immune cell and fibroblast proliferation contributing to the development of obliterative bronchiolitis.

[The influence of anxiety, depression and post traumatic stress disorder on quality of life after thoracic organ transplantation]. / Psychosoziale Belastung und Lebensqualität bei Patienten nach Herz- oder Lungentransplantation.

OBJECTIVES: This study examines stress factors, resources of coping, psychopathological symptoms and their influence on health-related quality of life (QoL) in patients after heart or lung transplantation. METHODS: 82 Patients were examined with the questionnaires SF-36 (QoL), HADS-D (anxiety and depression), IES-R and PTSS-10 (post traumatic stress disorder, PTSD) 32.3 (4-86) months after transplantation. Stress factors, resources and diagnostic criteria for PTSD were investigated by structured interview. RESULTS: In the entire sample, anxiety, depression and QoL were in the range of normal population. A subgroup of 13 patients with a PTSD diagnose had significantly reduced QoL. Anxiety and intrusion explained the 42 % variance of psychosocial score of QOL. CONCLUSIONS: There was a lower influence of depression on the medical score of QoL. Psychological symptoms such as anxiety, depression and PTSD significantly influence QoL after heart or lung transplantation. Patients with a PTSD diagnose had poor QoL. Screening for PTSD should be part of routine evaluation after organ transplantation.

Applying the Gender Lens to Risk Factors and Outcome after Adult Cardiac Surgery.

BACKGROUND: Applying the gender lens to risk factors and outcome after adult cardiac surgery is of major clinical interest, as the inclusion of sex and gender in research design and analysis may guarantee more comprehensive cardiovascular science and may consecutively result in a more effective surgical treatment as well as cost savings in cardiac surgery. METHODS: We have reviewed classical cardiovascular risk factors (diabetes, arterial hypertension, hyperlipidemia, smoking) according to a gender-based approach. Furthermore, we have examined comorbidities such as depression, renal insufficiency, and hormonal influences in regard to gender. Gender-sensitive economic aspects have been evaluated, surgical outcome has been analyzed, and cardiovascular research has been considered from a gender perspective. RESULTS: The influence of typical risk factors and outcome after cardiac surgery has been evaluated from a gender perspective, and the gender-specific distribution of these risk factors is reported on. The named comorbidities are listed. Economic aspects demonstrated a gender gap. Outcome after coronary and valvular surgeries as well as after heart transplantation are displayed in this regard. Results after postoperative use of intra-aortic balloon pump are shown. Gender-related aspects of clinical and biomedical cardiosurgical research are reported. CONCLUSIONS: Female gender has become an independent risk factor of survival after the majority of cardiosurgical procedures. Severely impaired left ventricular ejection fraction independently predicts survival in men, whereas age does in females.