Survival of patients with cardiomyopathies

Cardiomyopathies are a heterogeneous group of diseases. The main pathogenetic mechanism is myocardial damage due to genetic mutations. Cardiomyopathies are one of the leading causes of heart failure, sudden cardiac death, and life-threatening arrhythmias. Certain factors associated with poor prognosis determined the prognosis in this group of patients. Survival in different types of cardiomyopathies depends on the time of diagnosis and initial treatment. The types of cardiomyopathies discussed in this review are hypertrophic cardiomyopathy, dilative cardiomyopathy, restrictive cardiomyopathy, left ventricle non-compaction, and arrhythmogenic right ventricular cardiomyopathy.

Fibrin Sealant Patch for the Management of Intractable Bleeding From an LVAD Apex Cannula

Background: Intractable bleeding from the apical cannulation site of a left ventricular assist device (LVAD) is a dreaded complication. Case report: A 52-year-old male suffering from dilative cardiomyopathy (DCM) with fixed pulmonary hypertension underwent reoperative LVAD implantation after previous mitral valve surgery. The patient underwent three rethoracotomies for bleeding from the apex cannulation site without achieving hemostasis. Conventional techniques and application of fibrin sealants and polymeric sealing devices did not fix the problem. The bleeding stopped after application of the EVARREST® Fibrin Sealant Patch (FSP), and he needed no further transfusions. Conclusion: This patch might become a useful tool for intractable bleeding problems in LVAD surgery.

Comparison of periodontal parameters between patients with ischemic and dilative cardiomyopathy

Background This cross-sectional study aimed in the comparison of periodontal parameters, number of remaining teeth and oral behaviour between patients with ischemic- (ICM) and non-ischemic dilative cardiomyopathy (DCM). Methods Patients with HF from the Department for Cardiac Surgery at the Heart Center Leipzig were included. The two groups (ICM and DCM) were composed by matching according to age, gender and smoking habits. All participants received a comprehensive periodontal examination, including a periodontal probing on six measurement points of each tooth. Results A total of 226 patients (n = 113 each group) was included. Patients in DCM group used interdental cleaning significantly more often than ICM (23.9% vs. 12.5%, p = 0.04). The majority of patients in both groups (ICM: 83.6%, DCM: 84.6%, p = 0.23) were diagnosed with stage III–IV periodontitis. Periodontal parameters were comparable between groups (p > 0.05). Variance analysis revealed no influence of the group (ICM vs. DCM) on the number of remaining teeth (p = 0.16), periodontitis stage (p = 0.27) or the periodontal inflamed surface area (p = 0.62). Conclusions Patients with severe HF show high periodontal burden, without any differences between ICM and DCM group. Therefore, increased attention should be payed to periodontal health of patients with severe heart disease, irrespective of their underlying disease.

Functional Characterization of Cardiac Actin Mutants Causing Hypertrophic (p.A295S) and Dilative Cardiomyopathy (p.R312H and p.E361G)

The human mutant cardiac α-actins p.A295S or p.R312H (plus p.R312K) and p.E361G correlated with hypertrophic or dilative cardiomyopathy, respectively, were expressed by using the baculovirus/Sf21 insect cell system. After purification their biochemical and cell biological properties were analysed and compared to wild type (wt) cardiac actin identically obtained or conventionally isolated from bovine hearts. DNase I inhibition and their polymerization behaviour indicated that all c-α-actins had maintained their native state. Cardiomyopathy type specific differences were observed except for the p.R312K mutant, which behaved like wt c-α-actin. The extent of myosin-S1 ATPase stimulation by the c-actin variants and its Ca2+-sensitivity after decoration with tropomyosin (cTm) and troponin complex (cTn) varied being highest for the HCM p.A295S and lower for both DCM mutants. Similar Ca2+-sensitivity differences were observed by recording the fluorescence increase of pyrene-cTm in the absence or presence of myosin-S1 and/or the actin-binding N-terminal fragment of cardiac myosin binding protein C (N-cMyBP-C). Transfection experiments showed the incorporation of the c-actin variants into existing cytoskeletal elements of non-muscle cells. Wt and p.A295S c-α-actin preferably incorporated into the microfilament system and p.R312H and p.E361G into the submembranous actin network of MDCK cells. Transduction of neonatal rat cardiomyocytes with adenoviral constructs coding for HA-tagged c-α-actins showed their incorporation into thin filaments of nascent sarcomeric structures at their plus ends (Z-lines) except the p.E361G mutant, which preferably incorporated at the minus ends. Our data indicate functional differences of the c-α-actins that may be causative for the different cardiomyopathy phenotypes.

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension

The aim of our study was to analyse the protein expression of cartilage intermediate layer protein 1 (CILP1) in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH).Pulmonary artery banding was performed in 14 mice; another 9 mice underwent sham surgery. CILP1 protein expression was analysed in all hearts by western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left ventricular (LV) hypertrophy; 20 with dilative cardiomyopathy (DCM); 19 controls without LV or RV abnormalities)In mice, the amount of RV CILP1 was markedly higher after banding than after sham. Control patients had lower CILP1 serum levels than all other groups (p<0.001). CILP1 concentrations were higher in PH patients with maladaptive RV function than those with adaptive RV function (p<0.001), LV pressure overload (p<0.001), and DCM (p=0.003). CILP1 showed good predictive power for maladaptive RV in ROC analysis (AUC 0.79). There was no significant difference between the AUCs of CILP1 and NT-pro-BNP (AUC 0.82). High CILP1 (≥cut-off value for maladaptive RV of 4373 pg·mL−1) was associated with lower TAPSE/PASP ratios (p<0.001) and higher NT-pro-BNP levels (p<0.001).CILP1 is a novel biomarker of RV and LV pathological remodelling that is associated with RV maladaptation and ventriculoarterial uncoupling in patients with PH.

MIR1183 as a new tissue biomarker with triggered acute response and upregulation in chronic atrial and ventricular remodeling

Background and purpose Cardiac remodeling can be caused by a variety of insults linked to either stretch or tachycardia as a triggering mechanism. We aimed to investigate similarities and differences of the transcriptomic profiles in response to either acute stretch or tachycardia in isolated human atrial myocardium. In addition, we tested the highest acutely regulated target for its chronic regulation in human tissue with atrial or ventricular cardiac remodeling. Methods For acute trigger testing we applied either stretch (high pre- and afterload) or sustained tachycardia (2.5 Hz) for 6 hours in isolated atrial human trabeculae from cardiac surgery patients (all in sinus rhythm, SR). We performed gene expression profiling by RNA microarrays (n=5 per group) as a remodeling readout. For chronic regulation we performed qPCR of selected genes of interest in right atrial appendage tissue obtained from cardiac surgery patients with persistent atrial fibrillation compared to control patients with SR (n=6 per group), and also in ventricular tissue samples from failing hearts (from transplanted dilative cardiomyopathy patients) or non-failing control hearts (from multi-organ donors denied for transplantation), n=6 per group. Results The expression patterns of stretch and tachycardia were largely independent with 1305 transcripts regulated solely by stretch and 1837 transcripts by tachycardia with p&lt;0.05. In contrast, the fraction of commonly regulated genes was small (65 transcripts with p&lt;0.05). However, this fraction contained the strongest upregulated transcript, the microRNA precursor gene MIR1183, which was similarly upregulated by both triggers (4.1fold in stretch and 2.7fold in tachycardia, both p&lt;0.05). MIR1183 also showed upregulation in two important chronic remodeling settings: In atrial samples with persistent atrial fibrillation in comparison to sinus rhythm, it was 2.8fold upregulated, and in ventricular samples from dilative cardiomyopathy hearts it was 1.6fold upregulated (p&lt;0.05 for both). A functional role of MIR1183 in remodeling was also suggested by significant downregulation of its predicted downstream target genes ADAM20 and PLA2G7. Our ongoing research aims to confirm upregulation also in the circulating expression levels of the mature form of MIR1183 in human plasma samples in a cohort of atrial fibrillation patients with diseased atria, these findings will also be presented at scientific sessions. Conclusion Stretch and tachycardia show distinct transcriptomic signatures in human atrial trabeculae but share the strongest upregulated gene MIR1183 and consistent regulation of its downstream targets. This is present in an acute as well as chronic remodeling setting. Expression levels of MIR1183 might serve as a biomarker for atrial remodeling and to some extend ventricular remodeling and have potential functional significance in cardiac disease. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): Medical University of Graz

P362 Antimalarial-induced cardiomyopathy: retrospective case series

Background Antimalarial drugs chloroquine and hydroxychloroquine represent an important therapeutic option in autoimmune diseases. Rare cases of potentially lethal antimalarial-induced cardiomyopathy (AMIC) have been described. Pattern of minimal changes with wall hypertrophy, followed by restrictive and end-stage dilative cardiomyopathy was proposed in AMIC. Purpose Our aim was to identify patients with definite AMIC and characterize their clinical and imaging findings. Methods Retrospective analysis of admissions to Cardiology department from January 2010 to January 2019 was done to identify patients with definite diagnosis of AMIC based on positive endomyocardial biopsy. Clinical, echocardiographic, and cardiac magnetic resonance (CMR) imaging findings were reviewed if available. Results Three patients with biopsy proven diagnosis of AMIC were identified. Two patients, 62 and 76-year-old females, presented with signs of congestive heart failure, while the third, a 41-year-old man presented with chest pain and cardiac conduction abnormalities necessitating pacemaker implantation. All were treated with chloroquine phosphate. Both females had a history of pacemaker due to atrioventricular block. All had positive troponin and coronary artery disease was excluded. Echocardiography in the first case showed a severely dilated left ventricle (LV) with global hypokinesia and severe systolic dysfunction (LVEF 30%). CMR confirmed dilative cardiomyopathy, furthermore subepicardial late gadolinium enhancement (LGE) of the inferolateral LV wall and of the right ventricle free wall was present. In the second case a restrictive cardiomyopathy pattern was observed with mild biventricular systolic dysfunction and biatrial enlargement. CMR of this case was not available. Echocardiography in the third case showed a normal sized LV with mild diastolic and systolic dysfunction (LVEF 50%), along with septal hypokinesia. CMR showed patchy subepicardial and mid-wall LGE of the septum that was falsely attributed to myocarditis. Additionally, a chemical shift artefact suggestive of myocardial fatty infiltration (Image 1) was visible in the apical septum. After discontinuation of chloroquine two patients improved, while the first patient deteriorated and eventually succumbed to refractory heart failure. Conclusions Our three cases confirm high diversity of cardiac imaging findings in AMIC. Even mild non-specific findings such as LV systolic dysfunction or wall motion abnormalities in patients on antimalarial drugs should therefore be thoroughly investigated. CMR with non-ischaemic LGE pattern may aid in diagnosis, however definite diagnosis is currently possible only with endomyocardial biopsy. Novel imaging techniques, such as T1 mapping, have a potential to increase the diagnostic yield given the known patohistological similarities between AMIC and Anderson-Fabry disease. Abstract P362 Figure. Chemical shift artefact (arrow) in AMIC

Bilateral papillary muscle repositioning: successful repair of functional mitral regurgitation in dilative cardiomyopathy

OBJECTIVES: Functional mitral regurgitation (FMR) in patients with non-ischaemic dilative cardiomyopathy (DCM) is associated with heart failure and poor outcome. Aggressively undersized annuloplasty as an annular solution for a ventricular problem ameliorates heart failure but may be associated with recurrent FMR and does not improve survival. We sought to analyse if moderately undersized annuloplasty with repositioning of both papillary muscles can lead to improved valve stability and outcome in patients with DCM and FMR. METHODS: In 66 patients with DCM-associated FMR (age 66 ± 12 years, ejection fraction 29 ± 6% and mean pulmonary artery pressure 35 ± 11 mmHg) and severe leaflet tethering (tenting height ≥10 mm) bilateral papillary muscle repositioning was added to moderately undersized ring annuloplasty (median size 30 mm). Concomitant surgery included tricuspid valve repair in 86% of patients and atrial ablation in 44%. RESULTS: The early mortality rate was 9%. Overall 5-year freedom from all-cause death, left ventricular assist device implantation or heart transplant was 58% (95% confidence interval 45–71%). Six patients underwent reoperation (redo repair n = 4). Reverse remodelling was observed during follow-up in 66% of patients with decreasing left ventricular end-diastolic diameters (66 ± 5 to 61 ± 12 mm; P < 0.001) and left ventricular end-systolic diameters (56 ± 9 to 51 ± 14 mm; P = 0.001). Subgroup analyses (partial versus complete ring, preoperative left ventricular end-diastolic diameters <65 mm vs left ventricular end-diastolic diameter ≥65 mm) documented similar survival rates. A competing risks regression analysis identified cerebral vascular disease (P = 0.01), use of a partial ring (P = 0.03) and absence of tricuspid valve repair (P = 0.03) as independent predictors of death. CONCLUSIONS: The combination of bilateral papillary muscle repositioning and moderately undersized ring annuloplasty leads to stable mid-term repair results and reverse remodelling in patients with DCM and FMR and severe leaflet tethering.

An electrical nightmare: 105 inadequate ICD-shocks in a patient with broca aphasia

With a growing number of ICD-recipients, device complications are seen more frequently in the clinical setting and outpatient departments. Amongst the most severe are ICD-infections and inadequate shocks caused by oversensing of atrial tachycardia or lead fracture. We report on a 76-year-old female patient with dilative cardiomyopathy and broca aphasia after stroke, who experienced 105 consecutive inadequate ICDshocks due to cluster missensing of her fractured ICD-lead. The diagnosis was complicated and delayed by the patient’s aphasia emphasizing the need for intensified remote monitoring, especially in elderly and dependent patients.