Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis.

BACKGROUND: Percutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy. METHODS: Five patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters. RESULTS: Amyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow-up (P = .038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P = .02). CONCLUSION: PMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group.

Pentraxin-3 Predicts Short- and Mid-term Mortality in Patients with Sepsis and Septic Shock During Intensive Care Treatment.

BACKGROUND: The prognostic value of the acute phase protein Pentraxin 3 (PTX-3) is not well evaluated in patients with septic shock, which reveal an unacceptably high short- and long-term mortality. New Sepsis-3 definitions are not yet implemented in most biomarker studies. Therefore, this study assesses the prognostic value of PTX-3 for short- and mid-term mortality in patients with sepsis or septic shock, as defined by the latest definitions, treated at a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3, and 8. All-cause mortality was followed up to 30 days and at 6 months. RESULTS: On all three days, PTX-3 levels were able to discriminate non-survivors from survivors at 30 days and 6 months (AUC range: 0.59 - 0.70; 95% CI: 0.52 - 0.79; p ≤ 0.02). Highest PTX-3 levels within the fourth quartiles during the first week of ICU treatment were associated with an increased mortality rate at 30 days (OR = 7; 95% CI: 2.0 - 23.5; p ≤ 0.002) and at 6 months (OR = 5; 95% CI: 2.1 - 11.4; p ≤ 0.006). Additionally, the prognostic value of PTX-3 was proven for all patients as well as in subcohorts of patients with sepsis and septic shock, according to Sepsis-3 criteria, both in univariate and multivariate analyses for 30-day and 6-months all-cause mortality, especially predicting all-cause mortality in septic shock (HRs range: 1.0 - 2.9; 95% CI: 0.3 - 5.1; p ≤ 0.03). CONCLUSIONS: PTX-3 offers prognostic value for the prediction of short- and mid-term all-cause mortality in patients suffering from sepsis and septic shock according to the latest Sepsis-3 criteria.

Diagnostic value of Pentraxin-3 in patients with sepsis and septic shock in accordance with latest sepsis-3 definitions.

BACKGROUND: Pentraxin-3 (PTX-3) is an acute-phase protein involved in inflammatory and infectious processes. This study assesses its diagnostic and prognostic value in patients with sepsis or septic shock in a medical intensive care unit (ICU). METHODS: The study includes 213 ICU patients with clinical criteria of sepsis and septic shock. 77 donors served as controls. Plasma levels of PTX-3, procalcitonin (PCT) and interleukin-6 were measured on day 1, 3 and 8. RESULTS: PTX-3 correlated with higher lactate levels as well as with APACHE II and SOFA scores (p = 0.0001). PTX-3 levels of patients with sepsis or septic shock were consistently significantly higher than in the control group (p ≤ 0.001). Plasma levels were able to discriminate sepsis and septic shock significantly on day 1, 3 and 8 (range of AUC 0.73-0.92, p = 0.0001). Uniform cut-off levels were defined at ≥5 ng/ml for at least sepsis, ≥9 ng/ml for septic shock (p = 0.0001). CONCLUSION: PTX-3 reveals diagnostic value for sepsis and septic shock during the first week of intensive care treatment, comparable to interleukin-6 according to latest Sepsis-3 definitions. TRIAL REGISTRATION: NCT01535534 . Registered 14.02.2012.

Galectin-3 Reflects Left Atrial Function being Assessed by Cardiac Magnetic Resonance Imaging.

BACKGROUND: This study aims to evaluate the association between galectin-3 and left atrial function (LAF) in patients undergoing cMRI. METHODS: Patients undergoing cMRI were prospectively enrolled. Right ventricular dysfunction (< 50%) was excluded. Blood samples for biomarker measurements of galectin-3 and NT-proBNP were collected at the time of cMRI examination. RESULTS: A total of 84 patients were included. Median LVEF was 59% (IQR 51 - 64%). Galectin-3 was inversely correlated with overall LAF within a multivariable linear regression model (Beta -0.27; T -2.54; p = 0.01). Galectin-3 increased significantly according to the different stages of impaired LAF (p = 0.003) and was able to discriminate both patients with impaired LAF < 55% (AUC = 0.70, p = 0.002) and LAF < 45% (AUC = 0.69, p = 0.004). In multivariable logistic regression models, galectin-3 was still associated with impaired LAF (LAF < 55%: OR = 2.64, p = 0.07; LAF < 45%: OR = 6.65, p = 0.007). CONCLUSIONS: This study demonstrates that galectin-3 is able to reflect LAF being assessed by cMRI.

Re-do MitraClip in patients with functional mitral valve regurgitation and advanced heart failure.

AIM: Percutaneous mitral valve repair (PMVR) via MitraClip implantation is a therapeutic option for severe mitral regurgitation (MR) in advanced stages of heart failure (HF). However, progressive left ventricular dilation in these patients may lead to recurrent MR after PMVR and consequent re-do MitraClip implantation. Here, we describe the characteristics and outcomes of this clinical scenario. METHODS AND RESULTS: Patients with systolic HF and functional MR undergoing a re-do MitraClip procedure were retrospectively analysed. Inclusion criteria were age ≥18 years, technical, device and procedural success at first MitraClip procedure, functional MR and systolic HF with an ejection fraction (EF) of <45%. Seventeen out of 684 patients undergoing PMVR with the MitraClip device at our institution between September 2009 and July 2019 were included. All patients displayed advanced HF with an EF of 20% (±9.9) and highly elevated N-terminal pro-brain natriuretic peptide. Technical success of the re-do MitraClip procedure was 100%, whereas procedural and device success were only achieved in 11 patients (65%). Unsuccessful re-do procedures were related to lower EF and implantation of more than one clip at initial procedure. However, despite reduction in MR grade and no occurrence of significant mitral stenosis after the procedure, the mortality during 12 months follow-up remained high (8 of 17; 47%). CONCLUSIONS: In a cohort of patients with advanced HF undergoing PMVR, re-do MitraClip procedure was feasible, but procedural success was unsatisfactory and morbidity and mortality remained high, possibly reflecting the advanced stage of HF in these patients.

MitraClip implantation followed by insertion of a left ventricular assist device in patients with advanced heart failure.

AIMS: Mitral valve regurgitation (MR) is common in patients with advanced heart failure (HF). Percutaneous mitral valve repair (PMVR) via MitraClip (MC) has emerged as a feasible treatment strategy for these high-risk patients. However, as HF often further progresses, there is a frequent need for left ventricular assist device (LVAD) implantation in these patients. We aimed to investigate whether prior MC implantation affects the subsequent LVAD implantation and outcome. METHODS AND RESULTS: Thirty-seven patients with advanced HF and significant MR who underwent LVAD implantation were retrospectively analysed. Follow-up data were collected at 1 year after LVAD implantation. Primary endpoint was all-cause mortality. Secondary endpoint included peri-operative parameters and clinical development depicted as New York Heart Association (NYHA) class and Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) level. Seventeen patients initially received a MC device (MC group), resulting in a significant reduction in MR grade. After MC, NYHA class and INTERMACS level further worsened, leading to subsequent LVAD implantation after a median time of 475 days in the MC group. At LVAD implantation, overall characteristics were comparable with those of the patients undergoing LVAD implantation without prior MC placement (no-MC group). Procedural data revealed a higher incidence of right ventricular (RV) failure needing mechanical RV assistance and a longer need for nitric oxide ventilation in the MC group after LVAD implantation. One-year survival was slightly better in the no-MC group compared with the MC group [41% (n = 7/17) vs. 65% (n = 13/20); P = 0.15], albeit event-free survival was comparable between both groups, MC and no-MC. CONCLUSIONS: LVAD implantation after MC is feasible and safe. However, in patients with advanced HF and severe MR, PMVR may only delay a needed LVAD implantation and thereby lead to poorer peri-operative RV function and impaired outcome. Arguably, these patients might benefit from the timely management of advanced HF by the means of early LVAD implantation or heart transplantation.

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.

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.

Revisiting the prognostic value of monocyte chemotactic protein 1 and interleukin-6 in the sepsis-3 era.

BACKGROUND: Monocyte Chemotactic Protein 1 (MCP1) and latest sepsis-3 criteria are poorly represented within studies evaluating biomarkers in sepsis. Therefore, this study evaluates the prognostic value of MCP-1 compared to interleukin-6 (IL-6) in patients with sepsis and septic shock according to sepsis-3 criteria. METHODS: 136 patients with sepsis or septic shock were included within 24h of intensive care unit (ICU) admission. MCP-1, IL-6, procalcitonin (PCT), C-reactive protein (CRP) and white blood cells (WBC) were measured on days 1, 3 and 8. All-cause mortality was followed up at 30days and 6months. RESULTS: Both MCP-1 and IL-6 levels revealed valuable prognostic discrimination of 30-day and 6-months all-cause mortality on day 1 and 3 (MCP-1: range of AUCs 0.62-0.65, p<0.039; IL-6: range of AUCs 0.65-0.70, p<0.021) compared to PCT, CRP, SOFA and APACHE II score. MCP-1 levels within the 4th quartile revealed the highest mortality at 30days and 6months compared to patients with lower levels (range of hazard ratio (HR)=2.1-3.3, p<0.041). The prognostic value of MCP-1 sustained in multivariate regression models and was comparable to that of IL-6. CONCLUSION: Both MCP-1 and IL-6 revealed prognostic value for short- and mid-term all-cause mortality in patients with sepsis and septic shock according to latest sepsis-3 definitions.

Comparative analysis of high-sensitivity cardiac troponin I and T for their association with coronary computed tomography-assessed calcium scoring represented by the Agatston score.

BACKGROUND: This study evaluates the association between high-sensitivity cardiac troponin I (hs-cTnI) and T (hs-cTnT) and coronary calcium concentration (CAC) detected by coronary computed tomography (CCT) and evaluated with the Agatston score in patients with suspected coronary artery disease (CAD). METHODS: Patients undergoing CCT during routine clinical care were enrolled prospectively. CCT was indicated for patients with a low to intermediate pretest probability for CAD. Within 24 h of CCT examination, peripheral blood samples were taken to measure cardiac biomarkers hs-cTnI and hs-cTnT. RESULTS: A total of 76 patients were enrolled including 38% without detectable CAC, 36% with an Agatston score from 1 to 100, 17% from 101 to 400, and 9% with values ≥ 400. hs-cTnI was increasing alongside Agatston score and was able to differentiate between different groups of Agatston scores. Both hs-cTn discriminated values greater than 100 (hs-cTnI, AUC = 0.663; p = 0.032; hs-cTnT, AUC = 0.650; p = 0.048). In univariate and multivariate logistic regression models, hs-cTnT and hs-cTnI were significantly associated with increased Agatston scores. Patients with hs-cTnT ≥ 0.02 µg/l and hs-cTnI ≥ 5.5 ng/l were more likely to reveal values ≥ 400 (hs-cTnT; OR = 13.4; 95% CI 1.545-116.233; p = 0.019; hs-cTnI; OR = 8.8; 95% CI 1.183-65.475; p = 0.034). CONCLUSION: The present study shows that the Agatston score was significantly correlated with hs cardiac troponins, both in univariable and multivariable linear regression models. Hs-cTnI is able to discriminate between different Agatston values. The present results might reveal potential cut-off values for hs cardiac troponins regarding different Agatston values. Trial registration Cardiovascular Imaging and Biomarker Analyses (CIBER), NCT03074253 https://clinicaltrials.gov/ct2/show/record/NCT03074253.

Endothelial cell-specific molecule-1/endocan: Diagnostic and prognostic value in patients suffering from severe sepsis and septic shock.

PURPOSE: This study aims to assess the diagnostic and prognostic value of endocan in patients with severe sepsis or septic shock on a medical intensive care unit (ICU). METHODS: 150 patients suspected for at least severe sepsis were enrolled on a medical ICU. On days 1, 3, and 8, plasma levels of endocan, procalcitonin (PCT), and interleukin (IL)-6 were measured. Follow-up on all-cause mortality was performed after 30 days and 6 months. RESULTS: Endocan correlated with Acute Physiology and Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA), and Simplified Acute Physiology Score II (SAPS II) (P < .006). Endocan was higher in patients with at least severe sepsis compared with systemic inflammatory response syndrome (SIRS) or sepsis patients (P = .0006) on days 1, 3, and 8. With a minimum sensitivity of 70%, uniform cutoff levels were set for ≥ sepsis at 1.8 ng/mL, for ≥ severe sepsis at 2.6 ng/mL, for ≥ septic shock at 2.9 ng/mL. On day 1, endocan levels of the fourth quartile were significantly associated with 30-days and 6-months mortality compared to lower levels. After adjustment in Cox regressions, endocan still revealed prognostic value. CONCLUSIONS: Endocan showed diagnostic capacity to diagnose patients with severe sepsis and septic shock and revealed prognostic information for 30-days and 6-months all-cause mortality.