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Objectives: Data on the impact and course of uncorrected tricuspid regurgitation (TR) during left ventricular assist device (LVAD) implantation are scarce and inconsistent. This study explores the clinical impact and natural course of uncorrected TR in patients after LVAD implantation., Methods: The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients with LVAD implants without concomitant tricuspid valve surgery. A mediation model was developed to assess the association of TR with 30-day mortality via other risk factors. Generalized mixed models were used to model the course of post-LVAD TR. Joint models were used to perform sensitivity analyses., Results: A total of 2496 procedures were included (median age: 56 years; men: 83%). TR was not directly associated with higher 30-day mortality, but mediation analyses suggested an indirect association via preoperative elevated right atrial pressure and creatinine (P = 0.035) and bilirubin (P = 0.027) levels. Post-LVAD TR was also associated with increased late mortality [hazard ratio 1.16 (1.06-1.3); P = 0.001]. On average, uncorrected TR diminished after LVAD implantation. The probability of having moderate-to-severe TR immediately after an implant in patients with none-to-mild TR pre-LVAD was 10%; in patients with moderate-to-severe TR pre-LVAD, it was 35% and continued to decrease in patients with moderate-to-severe TR pre-LVAD, regardless of pre-LVAD right ventricular failure or pulmonary hypertension., Conclusions: Uncorrected TR pre-LVAD and post-LVAD is associated with increased early and late mortality. Nevertheless, on average, TR diminishes progressively without intervention after an LVAD implant. Therefore, these data suggest that patient selection for concomitant tricuspid valve surgery should not be based solely on TR grade., (© The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery.)

Purpose: Time of drug administration may significantly influence its effect. The aim of the present study was to investigate the effect of ASA (administrated in the morning or in the evening) on the anti-hypertensive effect and diurnal blood pressure profile in the high-risk group of cardiovascular patients., Methods: All patients (n = 114) had been diagnosed with coronary heart disease and arterial hypertension prior to the enrolment and had been treated with 75 mg per day of ASA in the morning. The patients were randomly assigned to one of the two study groups receiving 75 mg of ASA per day in a single antiplatelet therapy for 3 months in the morning (n = 58) or in the evening (n = 56). The control group (n = 61) consisted of patients with arterial hypertension but without coronary heart disease, not receiving ASA. In all the patients, during each visit, clinical blood pressure (BP) and ambulatory blood pressure measurements (ABPM) were performed., Results: There was a significant reduction in 24-h BP and blood pressure at night in the ASA group evening group compared with the ASA morning group and the control group., Conclusions: The present study demonstrated that compared with the use of ASA in the morning, its administration in the evening may lead to favourable drop in the ABPM and an improvement of the diurnal profile in the high-risk group of cardiovascular patients who are not naïve to ASA.

Cardiovascular diseases are the number one cause of morbidity and mortality worldwide, but the underlying molecular mechanisms remain not well understood. Cardiomyopathies are primary diseases of the heart muscle and contribute to high rates of heart failure and sudden cardiac deaths. Here, we distinguished four different genetic cardiomyopathies based on gene expression signatures. In this study, RNA-Sequencing was used to identify gene expression signatures in myocardial tissue of cardiomyopathy patients in comparison to non-failing human hearts. Therefore, expression differences between patients with specific affected genes, namely LMNA (lamin A/C), RBM20 (RNA binding motif protein 20), TTN (titin) and PKP2 (plakophilin 2) were investigated. We identified genotype-specific differences in regulated pathways, Gene Ontology (GO) terms as well as gene groups like secreted or regulatory proteins and potential candidate drug targets revealing specific molecular pathomechanisms for the four subtypes of genetic cardiomyopathies. Some regulated pathways are common between patients with mutations in RBM20 and TTN as the splice factor RBM20 targets amongst other genes TTN , leading to a similar response on pathway level, even though many differentially expressed genes (DEGs) still differ between both sample types. The myocardium of patients with mutations in LMNA is widely associated with upregulated genes/pathways involved in immune response, whereas mutations in PKP2 lead to a downregulation of genes of the extracellular matrix. Our results contribute to further understanding of the underlying molecular pathomechanisms aiming for novel and better treatment of genetic cardiomyopathies.

Severe mitral annulus calcifications significantly hinder surgical repair and replacement of the dysfunctional mitral valve. Herein, we present a novel surgical technique where we created an intra-atrial neomitral ring using a vascular Dacron graft in which a prosthetic valve was implanted. This approach is a simple alternative technique that can be used when anatomic prosthetic valve implantation is not feasible. Major assets of this approach are evasion of extensive debridement, implantation of an adequately sized prosthesis, and prosthetic material availability., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The clinical profile of left ventricular assist device (LVAD) candidates is rapidly changing, with increasing proportion of patients in more stable clinical conditions. However, early postoperative right ventricular failure (eRVF) is still one of the cornerstones associated with increased mortality and the preoperative recognition of associated risk factors remains challenging. The aim of this study was to identify predictive parameters for eRVF after LVAD implantation in patients with preoperative intermediate Intermacs (InM) risk profile 3-5., Methods: Preoperative laboratory, echocardiography, and right heart catheterization data collected from 80 patients with InM profile 3-5 before LVAD implantation were retrospectively tested with respect to their ability to predict the risk for eRVF after the implantation of a continuous-flow LVAD., Results: Preoperative higher bilirubin and blood urea nitrogen (BUN) levels, higher Model for End-stage Liver Disease score, lower estimated glomerular filtration rate, and higher central venous pressure to pulmonary capillary wedge pressure ratio (CVP/PCWP) were associated to higher risk of eRVF. Regarding the echocardiographic assessment, higher end diastolic linear dimensions of the RV, higher basal end diastolic RV linear dimension to LV ratio, severe tricuspid regurgitation, lower tricuspid annular plane systolic excursion, and lower RV fractional area contraction identified patients with higher risk for eRVF. In the multivariable analysis, a CVP/CPWP > 0.55 (odds ratio [OR]: 4, 95% confidence interval [CII]: 1.4-11.8;P = .01) and BUN > 44.5 mg/dL (OR: 6.6, 95% CI: 1.51-23; P = .011) independently predicted the risk of eRVF., Conclusion: Preoperative BUN > 44.5 mg/dL and CVP/PCWP > 0.55 are associated to an increased risk of eRVF following LVAD implantation in intermediate InM patients., (© 2020 The Authors. Journal of Cardiac Surgery published by Wiley Periodicals LLC.)

Aims: We aimed to unravel the genetic, molecular and cellular pathomechanisms of DSC2 truncation variants leading to arrhythmogenic cardiomyopathy (ACM)., Methods and Results: We report a homozygous 4-bp DSC2 deletion variant c.1913_1916delAGAA, p.Q638LfsX647 hom causing a frameshift carried by an ACM patient. Whole exome sequencing and comparative genomic hybridization analysis support a loss of heterozygosity in a large segment of chromosome 18 indicating segmental interstitial uniparental isodisomy (UPD). Ultrastructural analysis of the explanted myocardium from a mutation carrier using transmission electron microscopy revealed a partially widening of the intercalated disc. Using qRT-PCR we demonstrated that DSC2 mRNA expression was substantially decreased in the explanted myocardial tissue of the homozygous carrier compared to controls. Western blot analysis revealed absence of both full-length desmocollin-2 isoforms. Only a weak expression of the truncated form of desmocollin-2 was detectable. Immunohistochemistry showed that the truncated form of desmocollin-2 did not localize at the intercalated discs. In vitro, transfection experiments using induced pluripotent stem cell derived cardiomyocytes and HT-1080 cells demonstrated an obvious absence of the mutant truncated desmocollin-2 at the plasma membrane. Immunoprecipitation in combination with fluorescence measurements and Western blot analyses revealed an abnormal secretion of the truncated desmocollin-2., Conclusion: In summary, we unraveled segmental UPD as the likely genetic reason for a small homozygous DSC2 deletion. We conclude that a combination of nonsense mediated mRNA decay and extracellular secretion is involved in DSC2 related ACM., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: Tricuspid regurgitation (TR) is common in patients receiving a left ventricular assist device (LVAD). Controversy exists as to whether concomitant tricuspid valve surgery (TVS) is beneficial in currently treated patients. Therefore, our goal was to investigate the effect of TVS concomitant with a LVAD implant., Methods: The European Registry for Patients with Mechanical Circulatory Support was used to identify adult patients. Matched patients with and without concomitant TVS were compared using a propensity score matching strategy., Results: In total, 3323 patients underwent LVAD implantation of which 299 (9%) had TVS. After matching, 258 patients without TVS were matched to 258 patients with TVS. In the matched population, hospital deaths, days on inotropic support, temporary right ventricular assist device implants and hospital stay were comparable, whereas stay in the intensive care unit was higher in the TVS cohort (11 vs 15 days; P = 0.026). Late deaths (P = 0.17), cumulative incidence of unexpected hospital readmission (P = 0.15) and right heart failure (P = 0.55) were comparable between patients with and without concomitant TVS. In the matched population, probability of moderate-to-severe TR immediately after surgery was lower in patients with concomitant TVS compared to patients without TVS (33% vs 70%; P = 0.001). Nevertheless, the probability of moderate-to-severe TR decreased more quickly in patients without TVS (P = 0.030), resulting in comparable probabilities of moderate-to-severe TR within 1.5 years of follow-up., Conclusions: In matched patients, TVS concomitant with LVAD implant does not seem to be associated with better clinical outcomes. Concomitant TVS reduced TR significantly early after LVAD implant; however, differences in probability of TR disappeared during the follow-up period., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Here, we present a small Iranian family, where the index patient received a diagnosis of restrictive cardiomyopathy (RCM) in combination with atrioventricular (AV) block. Genetic analysis revealed a novel homozygous missense mutation in the DES gene (c.364T > C; p.Y122H), which is absent in human population databases. The mutation is localized in the highly conserved coil-1 desmin subdomain. In silico, prediction tools indicate a deleterious effect of the desmin ( DES ) mutation p.Y122H. Consequently, we generated an expression plasmid encoding the mutant and wildtype desmin formed, and analyzed the filament formation in vitro in cardiomyocytes derived from induced pluripotent stem cells and HT-1080 cells. Confocal microscopy revealed a severe filament assembly defect of mutant desmin supporting the pathogenicity of the DES mutation, p.Y122H, whereas the wildtype desmin formed regular intermediate filaments. According to the guidelines of the American College of Medical Genetics and Genomics, we classified this mutation, therefore, as a novel pathogenic mutation. Our report could point to a recessive inheritance of the DES mutation, p.Y122H, which is important for the genetic counseling of similar families with restrictive cardiomyopathy caused by DES mutations.

The obstructive sleep apnea (OSA) is highly associated with various significant cardiovascular outcomes such as resistant hypertension (RAH). Despite this, as of now the relationship between high night-time blood pressure (BP) and left ventricular hypertrophy (LVH) in patients with OSA and RAH is not fully understood. The aim of this study was to assess the influence of the addition of eplerenone to a standard antihypertensive therapy on parameters of 24-h ambulatory blood pressure measurement (ABPM) as well as on the results of echocardiography and polysomnography in patients with OSA and RAH. The patients were randomly assigned to one of the two study groups: the treatment group, receiving 50 mg/d eplerenone orally for 6 months ( n = 51) and the control group, remaining on their standard antihypertensive therapy ( n = 51). After that period, a significant reduction in the night-time BP parameters in the treatment group including an increased night blood pressure fall from 4.6 to 8.9% was noted. Additionally, the number of non-dipper patients was reduced by 45.1%. The treatment group also revealed a decrease in left ventricular hypertrophy and in the apnea-hypopnea index (AHI) with a positive correlation being observed between these two parameters. This study is the first to report the improvement of the circadian BP profile and the improvement of the left ventricle geometry in patients with OSA and RAH following the addition of selective mineralocorticoid receptor antagonists to antihypertensive therapy.

Background: Hypertrophic cardiomyopathy (HCM) is a genetic cardiomyopathy with a prevalence of about 1:200. It is characterized by left ventricular hypertrophy, diastolic dysfunction and interstitial fibrosis; HCM might lead to sudden cardiac death (SCD) especially in the young. Due to low autopsy frequencies of sudden unexplained deaths (SUD) the true prevalence of SCD and especially of HCM among SUD remains unclear. Even in cases of proven SCD genetic testing is not a routine procedure precluding appropriate risk stratification and counseling of relatives., Methods: Here we report a case of SCD in a 19-year-old investigated by combined forensic and molecular autopsy., Results: During autopsy of the index-patient HCM was detected. As no other possible cause of death could be uncovered by forensic autopsy the event was classified as SCD. Molecular autopsy identified two (probably) pathogenic genetic variants in FHL1 and MYBPC3. The MYBPC3 variant had an incomplete penetrance. The FHL1 variant was a de novo mutation. We detected reduced FHL1 mRNA levels and no FHL1 protein in muscle samples suggesting nonsense-mediated mRNA decay and/or degradation of the truncated protein in the SCD victim revealing a plausible disease mechanism., Conclusion: The identification of the genetic cause of the SCD contributed to the rational counseling of the relatives and risk assessment within the family. Furthermore our study revealed evidences for the pathomechanism of FHL1 mutations., (© 2019 Herz- & Diabeteszentrum NRW, Ruhr-Universitat Bochum. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Heart failure is a clinical syndrome of multifactorial aetiology with typical symptoms and diverse prevalence depending on the world region, reaching more than 10% in the population over 70 years of age. The prognosis, in spite of a dynamic improve- ment in medical therapy, remains poor. The only treatment for these patients is heart transplantation, however, its availability is highly limited because of the shortage of donor organs. Mechanical circulatory support can offer an alternative treatment for this patient cohort. In this review the authors discuss the present indications for, as well as results and complications of different types of long-term mechanical circulatory support. The long-term survival in patients receiving this therapy, in spite of many complication, is much better than in those receiving medical treatment. The use of mechanical circulatory support is an established treatment option for many patients with end-stage heart failure. The most important issue for the cardiologist is to identify patients eligible for this therapy in order to give them a chance for a longer life and better quality of life.

Background: Acetylsalicylic acid (ASA) is one of the basic drugs used in the secondary prevention of coronary artery disease (CAD), and in most cases it is taken in the morning in one daily dose. It is suggested that the morning peak of platelet aggregation is responsible for the occurrence of myocardial infarctions and strokes. Hence, the aim of the study was to observe the effect of ASA (morning vs. evening) dosing on the anti-aggregative effect of platelets in patients with CAD and arterial hypertension (AH)., Methods: The study involved 175 patients with CAD and AH. Patients were randomly assigned to one of two study groups, taking ASA in the morning or in the evening. The patients had two visits, one baseline and another after 3 months from changing the time of ASA dosage. The platelet aggregation was determined using the VerifyNow analyzer., Results: In the ASA evening group, a significant reduction in platelet aggregation was obtained. In the ASA morning group, a significant difference in response to ASA was observed, depending on sex. In men, the reactivity of platelets decreased, but in women it increased., Conclusions: In the group of patients with CAD and AH, bedtime ASA dosing is associated with a significant reduction in platelet aggregation. The response to ASA may differ between sexes. The benefit gained by changing the drug administration from the morning to the evening is greater in women.

The number of implanted left ventricular assist devices is increasing systematically. Novel systems are being introduced and survival rates are improving, but complications, such as heart failure, leading to high early and late mortality still exist. Echocardiography is the preferred method for assessing the anatomy and function of the right ventricle (RV). In spite of the many methods available for use, including 2- and 3-dimensional techniques, assessment of the RV remains challenging. In this review, we present echocardiographic parameters that are most often used to assess right ventricular anatomy and function, and analyse their ability to predict right heart failure after the implantation of a left ventricular assist device.

Background: DES mutations cause different cardiac and skeletal myopathies. Most of them are missense mutations., Methods: Using a next-generation sequencing cardiac 174 gene panel, we identified a novel heterozygous in-frame indel mutation (DES-c.493_520del28insGCGT, p.Q165_A174delinsAS) in a Caucasian patient with cardiomyopathy in combination with atrioventricular block and skeletal myopathy. This indel mutation is located in the coding region of the first exon. Family anamnesis revealed a history of sudden cardiac death. We performed cell transfection experiments and in vitro assembly experiments to prove the pathogenicity of this novel DES indel mutation., Results: These experiments revealed a severe filament formation defect of mutant desmin supporting the pathogenicity. In addition, we labeled a skeletal muscle biopsy from the mutation carrier revealing cytoplasmic desmin positive protein aggregates. In summary, we identified and functionally characterized a pathogenic DES indel mutation causing cardiac and skeletal myopathy., Conclusion: Our study has relevance for the clinical and genetic interpretation of further DES indel mutations causing cardiac or skeletal myopathies and might be helpful for risk stratification., (© 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.)

Objectives: Heart transplantation (HT) and ventricular assist devices (VAD) for the management of end-stage heart failure have not been directly compared. We compare the outcomes and use of resources with these 2 strategies in 2 European countries with different allocation systems., Methods: We studied 83 patients managed by VAD as the first option in Bad Oeynhausen, Germany (Group I) and 141 managed with either HT or medical therapy, as the first option, in Paris, France (Group II). The primary end-point was 2-year survival. Kaplan-Meier analyses were performed after the application of propensity score weights to mitigate the effects of non-random group assignment. The secondary end-points were resource utilization and costs. Subgroup analyses were performed for patients undergoing HT and patients treated with inotropes at the enrolment time., Results: The Group I patients were more severely ill and haemodynamically compromised, and 28% subsequently underwent HT vs 55% primary HT in Group II, P < 0.001. The adjusted probability of survival was 44% in Group I vs 70% in Group II, P <0.0001. The mean cumulated 2-year costs were €281 361 ± 156 223 in Group I and €47 638 ± 35 061 in Group II, P < 0.0001. Among patients who underwent HT, the adjusted probability of survival in Group I (n = 23) versus Group II (n = 78) was 76% versus 68%, respectively (0.09), though it differed in the inotrope-treated subgroups (77% in Group I vs 67% in Group II, P = 0.04)., Conclusions: HT should remain the first option for end-stage heart failure patients, associated with improved outcomes and better cost-effectiveness profile. VAD devices represent an option when transplant is not possible or when patient presentation is not optimal., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Cardiomyopathies might lead to end-stage heart disease with the requirement of drastic treatments like bridging up to transplant or heart transplantation. A not precisely known proportion of these diseases are genetically determined. We genotyped 43 index-patients (30 DCM, 10 ARVC, 3 RCM) with advanced or end stage cardiomyopathy using a gene panel which covered 46 known cardiomyopathy disease genes. Fifty-three variants with possible impact on disease in 33 patients were identified. Of these 27 (51%) were classified as likely pathogenic or pathogenic in the MYH7, MYL2, MYL3, NEXN, TNNC1, TNNI3, DES, LMNA, PKP2, PLN, RBM20, TTN, and CRYAB genes. Fifty-six percent (n = 24) of index-patients carried a likely pathogenic or pathogenic mutation. Of these 75% (n = 18) were familial and 25% (n = 6) sporadic cases. However, severe cardiomyopathy seemed to be not characterized by a specific mutation profile. Remarkably, we identified a novel homozygous PKP2-missense variant in a large consanguineous family with sudden death in early childhood and several members with heart transplantation in adolescent age.

Aims: Coronary artery disease accounts for the majority of sudden cardiac deaths (SCD) in the older population whereas cardiomyopathies and arrhythmogenic abnormalities predominate in younger SCD victims (<35 years) with a significant genetic component. The elucidation of the pathogenetic cause of death might be relevant for the prevention of further deaths within affected families. Aim of this study was to determine the portion of underlying genetic heart diseases among unexplained putative SCD cases from a large German forensic department., Methods and Results: We included 10 forensic cases of sudden unexplained death (SUD) victims aged 19-40 years, who died by SCD due to forensic autopsy. DNA was analysed by next generation panel sequencing of 174 candidate genes for channelopathies and cardiomyopathies. Cardiological examinations, genetic counselling, and subsequent genetic testing were offered to all affected families. We identified within 1 year 10 cases of SUD among 172 forensic cases. Evidence for a genetic disposition was found in 8 of 10 (80%) cases, with pathogenic mutations in 3 and variants of uncertain significance in 5 of SCD cases. Subsequent selective screening of family members revealed two additional mutation carriers., Conclusion: The study provides strong evidence that molecular genetics improves the post mortem diagnosis of fatal genetic heart diseases among SUD victims. Molecular genetics should be integrated in forensic and pathological routine practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Restrictive cardiomyopathy (RCM) is a rare heart disease characterized by diastolic dysfunction and atrial enlargement. The genetic etiology of RCM is not completely known. We identified by a next-generation sequencing panel the novel CRYAB missense mutation c.326A>G, p.D109G in a small family with RCM in combination with skeletal myopathy with an early onset of the disease. CRYAB encodes αB-crystallin, a member of the small heat shock protein family, which is highly expressed in cardiac and skeletal muscle. In addition to in silico prediction analysis, our structural analysis of explanted myocardial tissue of a mutation carrier as well as in vitro cell transfection experiments revealed abnormal protein aggregation of mutant αB-crystallin and desmin, supporting the deleterious effect of this novel mutation. In conclusion, CRYAB appears to be a novel RCM gene, which might have relevance for the molecular diagnosis and the genetic counseling of further affected families in the future., (© 2017 Wiley Periodicals, Inc.)

Objectives: The number of implanted biological valves for treatment of valvular heart disease is growing and a percentage of these patients will eventually undergo a transcatheter valve-in-valve (ViV) procedure. Some of these patients will represent challenging cases. The aim of this study was to develop a feasible algorithm to plan and in vitro simulate a new interventional procedure to improve patient outcome., Methods: In addition to standard diagnostic routine, our algorithm includes 3D printing of the annulus, hydrodynamic measurements and high-speed analysis of leaflet kinematics after simulation of the procedure in different prosthesis positions as well as X-ray imaging of the most suitable valve position to create a 'blueprint' for the patient procedure., Results: This algorithm was developed for a patient with a degenerated Perceval aortic sutureless prosthesis requiring a ViV procedure. Different ViV procedures were assessed in the algorithm and based on these results the best option for the patient was chosen. The actual procedure went exactly as planned with help of this algorithm., Conclusions: Here we have developed a new technically feasible algorithm simulating important aspects of a novel interventional procedure prior to the actual procedure. This algorithm can be applied to virtually all patients requiring a novel interventional procedure to help identify risks and find optimal parameters for prosthesis selection and placement in order to maximize safety for the patient., (© The Author 2015. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Right ventricular failure (RVF) is a major cause of morbidity and mortality in left ventricular assist device (LVAD) recipients., Objectives: To identify preoperative echocardiographic predictors of post-LVAD RVF., Methods: Data were collected for 42 patients undergoing LVAD implantation in Germany. RVF was defined as the need for placement of a temporary right ventricular assist device or the use of inotropic agents for 14 days. Data for RVF patients were compared with those for patients without RVF. A score (ARVADE) was established with independent predictors of RVF by rounding the exponentiated regression model coefficients to the nearest 0.5., Results: RVF occurred in 24 of 42 LVAD patients. Univariate analysis identified the following measurements as RVF risk factors: basal right ventricular end-diastolic diameter (RVEDD), minimal inferior vena cava diameter, pulsed Doppler transmitral E wave (Em), Em/tissue Doppler lateral systolic velocity (SLAT) ratio and Em/tissue Doppler septal systolic velocity (SSEPT) ratio. Em/SLAT≥18.5 (relative risk [RR] 2.78, 95% confidence interval [CI] 1.38-5.60; P=0.001), RVEDD≥50 mm (RR 1.97, 95% CI 1.21-3.20; P=0.008) and INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) level 1 (RR 1.74, 95% CI 1.04-2.91; P=0.04) were independent predictors of RVF. An ARVADE score>3 predicted the occurrence of post-implantation RVF with a sensitivity of 89% and a specificity of 74%., Conclusion: The ARVADE score, combining one clinical variable and three echocardiographic measurements, is potentially useful for selecting patients for the implantation of an assist device., (Copyright © 2015 Elsevier Masson SAS. All rights reserved.)

Objectives: We investigated the impact of inodilators on the accuracy of E/e' ratio as a surrogate for pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure., Setting: The ratio of early diastolic transmitral flow velocity to tissue Doppler mitral annular early diastolic velocity, E/e', and pulmonary artery occlusion pressure have been shown to be correlated. The validity of E/e' for predicting pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure was recently challenged, but the influence of inodilators was not taken into account, despite the reported influence of these drugs on left ventricular relaxation properties., Patients and Intervention: Invasive hemodynamic monitoring and echocardiographic data were collected prospectively from 39 patients with decompensated end-stage systolic heart failure (92% male), aged 56 ± 13 years. These patients had dilated ventricles with a low cardiac index (1.9 ± 0.6 L/min/m) and high pulmonary artery occlusion pressure (22 ± 8 mm Hg), and 90% required inodilator support during hospitalization., Measurements and Main Results: The correlation between septal E/e' and pulmonary artery occlusion pressure was good for examinations in the absence of inodilators (n = 21) (r = 0.7; p < 0.001), but no correlation was found when inodilators were used (n = 31). Lateral and mean E/e' were poorly correlated with pulmonary artery occlusion pressure, if at all, in both cases., Conclusions: By modifying ventricular relaxation properties and the influence of filling pressure on e', inodilator agents severely impair the correlation between E/e' and pulmonary artery occlusion pressure in patients with decompensated end-stage systolic heart failure.

Right ventricular failure (RVF) exposes ventricular assist device (VAD) recipients to a high risk of death, but its management has not yet been standardized. We report three separate management strategies used for VAD recipients that present with RVF at a single center: 1) Thoratec paracorporeal biventricular VAD implantation, 2) left ventricular assist device (LVAD) implantation with temporary CentriMag right ventricular assist device (RVAD), and 3) LVAD combined with inotropic therapy. We retrospectively compared the preoperative data, the clinical outcomes, and the rates of adverse events in 84 biventricular assist device (BiVAD) recipients and 89 LVAD recipients presenting with postoperative RVF (57 were treated with a temporary RVAD and 32 were managed medically). Risk factors for death were analyzed. The BiVAD recipients were significantly younger, more critically ill at the time of device implantation, and required extracorporeal membrane oxygenation, an intraaortic balloon pump, mechanical ventilation, inotropes, or cardiopulmonary resuscitation significantly more often (at the time of device implant) than the LVAD recipients with RVF. The 6 month mortality was comparable in the two groups: 44 BiVAD patients (52%) and 38 LVAD patients (43%). Age, previous cardiac surgery, low platelet count, increased creatinine levels, the use of preoperative mechanical ventilation, and the need for a temporary RVAD were associated with 6 month mortality. The occurrence of RVF at the time of device implantation is a severe situation; it is associated with excess mortality, even if it is managed using a BiVAD or a LVAD with a temporary RVAD, probably because of the high preoperative risk profiles of the patients. In all cases, RVF must be managed quickly.

In this case report, we present a patient 28 years after mitral valve replacement with the Starr-Edwards prosthesis complicated by periprosthetic leak with severe aortic stenosis and moderate tricuspid regurgitation. We successfully repaired the periprosthetic regurgitation in a patient with extensive mitral annular calcification, without replacement of the valve. No apparent structural deterioration on the caged-ball valve was found. Moreover, aortic valve replacement and tricuspid annuloplasty were performed. One month after reoperation, the patient remained stable with improved clinical status and without any evidence for further paravalvular leak.

A 68-year-old man was admitted to the hospital 4 months after HeartMate II ventricular assist device implantation, because his clinical status had deteriorated and his levels of lactate dehydrogenase and free hemoglobin had increased. Transthoracic echocardiography performed at admission revealed decreased basic diastolic continuous flow velocity with a pulsatile increase in flow velocity during ventricular contraction in both inflow and outflow cannulas. Twelve hours after beginning lytic therapy, basal diastolic continuous flow velocity had increased, and the amplitude between diastolic and systolic flow velocity had decreased. The clinical status of the patient improved, and his lactate dehydrogenase decreased. A decrease in basal diastolic flow may be a valuable marker of flow disturbance in continuous flow ventricular assist devices., (Copyright © 2010 American Society of Echocardiography. Published by Mosby, Inc. All rights reserved.)

(Echocardiography, ****;**:E1-E2).

Background: Sleep-related breathing disorders (SRBD) are the additional factor related to poor prognosis in patients with cardiovascular disorders. The apnoea/hypopnoea index (AHI), describing the number of apnoea and hypopnoea episodes per one hour of sleep, has been used as a marker of severity of the disorder. The disease is present in 4% of men and 2% of women above 40 years of age. However, SRBD are diagnosed in less than 3% of patients with this syndrome due to lack of awareness of the disease among health care practitioners and patients. Polysomnography (PSG) has been used as a golden standard for detecting SRBD, however this test is available only in selected centres. Therefore, a simple, fast and inexpensive test for screening for SRBD is necessary. Respiratory activity influences the amplitude of ECG signal whereas heart rate variability (HRV) depicts the activity of the autonomic nervous system. These associations have been used to develop a new method for detection of SRBD involving analysis of HRV and morphology of ECG signal in ECG monitoring., Aim: Assessment of accuracy of SRBD detection using estimated AHI (Est.AHI), calculated from Holter ECG recordings., Methods: In a study group consisting of 74 patients tested for SRBD, simultaneous PSG and 24-hour ECG monitoring were performed. Following PSG, AHI for each patient was calculated. According to the AHI values patients were classified as SRBD patients (AHI >15), non-SRBD patients (AHI <5), whereas 12 individuals had borderline SRBD (5< or = AHI < or =15). Age, prevalence of concomitant disorders and treatment were similar in all groups. In all individuals the Est.AHI value was calculated based on ECG recording. Considering the AHI value as a reference parameter discriminating SDB and non-SRBD patients, the number of false positive and false negative results for detecting SDB with the Est.AHI was calculated. Moreover, the SRBD detection accuracy using the Est.AHI calculation was evaluated by the receiver-operator characteristic (ROC) curves which were used to calculate area under curve (AUC), sensitivity, specificity, as well as positive (PPV) and negative (NPV) predictive values for optimal cut-off value., Results: According to Est.AHI, 50 (68%) patients were correctly diagnosed. The ROC analysis showed high accuracy of SRBD detection using Est.AHI: AUC - 0.91 with sensitivity - 91.2%, specificity - 87.5%, PPV - 88.6%, and NPV - 88.9%. The cut-off value of Est.AHI set at 17 was optimal for the differentiation between patients with or without SRBD., Conclusions: The Est.AHI calculated with the Lifescreen Apnea software from Holter ECG is an accurate, specific and sensitive method for the detection and classification of obstructive and mixed SRBD.

Unlabelled: A prospective collection of clinical (history), electrocardiography (ECG), exercise electrocardiography (EE), dobutamine stress echocardiography (SE) and catheterization data was performed in 551 patients with chest pain regarded as definite or probable stable angina pectoris. All patients (65% male) without prior history of myocardial infarction undergone clinical evaluation: chest pain classification according to Diamond, ECG, EE (regarded as positive on the basis of > or = 1 mm ST-depression), SE (ischemia was defined as new or worsening wall motion abnormalities using a 16-segment model) and coronary angiography (CA):CAD was defined as > or = 50% narrowing of at least one major vessel. Sensitivity and specificity of ECG, EE, SE was calculated: and results are as follows respectively: 23% and 87%, 93% and 21%, 85% and 69%. On the basis of these results with implication of probability analysis two algorithms were developed by computer program. They incorporated pretest variables: age, gender, chest pain classification, ECG and results of one or two non-invasive tests: EE and (or) SE. The sensitivity and specificity of the algorithm is 96% and 44%., Conclusions: 1. Chest pain characteristics remains an effective tool for estimating probability of CAD. 2. The diagnostic value of resting electrocardiography in stable CAD is low. 3. SE has comparably sensitivity but significantly higher specificity than EE. 4. We demonstrated that when the likelihood of CAD is high on the basis of initial evaluation, diagnostic non-invasive testing is not indicated before CA. 5. When the probability is intermediate or low, implementation of first choice test should be different in women (SE) and men (EE).

The purpose of this study was to examine the early and late results of CABG in patients with left ventricular ejection fraction (LVEF) lower than 40%. This study comprised 128 patients (114 male and 14 female) at age from 41 to 75 years (mean 58.3 +/- 7.9). Before operation 115 patients (89.8%) were in CCS class III or IV. Before operation in all patients coronary arteriography with left-sided ventriculography were performed. In 12 patients myocardial perfusion in SPECT with Tc-99m-MIBI was assessed. Perioperative mortality in whole group was 12.5% (16 patients). The lowest (9.2%) was in subgroup with LVEF from 0.31 to 0.4 and the highest (27.3%) in patients with LVEF below 0.2. In 8 patients death was caused by low cardiac output, in 4 by ventricular fibrillation, in the others by renal failure or cerebral stroke (2 patients in each). In 45 patients (35.2%) postoperative low cardiac output was observed. In 41 patients was treated with the use of intraaortic balloon pumping (IABP). Twenty seven (65.9%) patients with IABP survived. During follow-up died 5 pts. 24-months probability of survival calculated from Kaplan-Meier method was 82.4%. In follow-up 80.9% of patients were in CCS class I and II. In SPECT, four months after CABG significantly more segments of left ventricle with normal perfusion (45% vs 53%; p < 0.05) were observed. Patients with LVEF < 40% are at higher operative risk because of often postoperative low output syndrome. Low output syndrome can by successfully treated with IABP. CABG significantly improves circulatory sufficiency in patients with LVEF < 40%.

Unlabelled: The relation of chest pain characteristics and other features of the history of disease to coronary angiograms was assessed in 551 patients with chest pain regarded as definite or probable stable angina pectoris. A standardised questionnaire was used to record demographic details and chest pain characteristics of interviewed patients. The differentiation between typical, atypical or nonanginal pain was based on classification proposed by Diamond. The indications for catheterization in each patient were determined at the discretion of the attending physician. All patients underwent diagnostic coronary angiography (clinically important coronary artery disease was defined as > 50 per cent narrowing of the diameter of at least one major vessel or > or = 50 per cent of the left main coronary artery)., Conclusion: Chest pain characteristics remains an effective tool for estimating probability of coronary artery disease.

Background and Aim of the Study: Ostium primum atrial septal defect (ASD I) is very rarely observed in the adults. Although ASD I was first corrected surgically almost 50 years ago, the efficacy of surgical treatment in adults has not been well documented. Thus, the long-term outcome of patients aged over 20 years and having surgical repair of ASD I was examined., Methods: Fifteen patients (10 males, five females; mean age 31.4+/-13.1 years; range: 20 to 56 years) who had surgical repair of ASD I between 1982 and 2000 were followed. All patients were examined physically and underwent chest radiography, ECG and echocardiography (cross-sectional and Doppler) before and after surgery. Autologous pericardium was used to close the defect in 14 patients, and a direct suture was used in one patient. Mitral valvuloplasty (repair of the cleft) was performed in 12 patients, and De Vega annuloplasty in eight., Results: There were no hospital deaths. In one case a pacemaker was implanted five days after surgery because of complete heart block. Preoperatively, nine patients (60%) were in NYHA classes III and IV; at the end of follow up, 14 (93.3%) were in classes I and II. Preoperatively, 13 patients had sinus rhythm, and one each had atrial fibrillation (AF) and rhythm from the atrioventricular sinus. During follow up, three patients developed AF which was treated successfully with electrical cardioversion. The preoperative mean cardiac volume index of 695 +/- 216 ml/m(2) was reduced significantly after repair to 523 +/- 108 ml/m(2) (p < 0.05). Before surgery, mitral regurgitation was observed (severe in five cases, moderate in seven, mild in three). Postoperatively, a residual intracardiac shunt was identified in one case. Postoperative mitral regurgitation was noted in six patients (moderate in two, mild in four). The right ventricular dimension was decreased significantly, from 5.0 +/- 1.5 mm before surgery to 3.2 +/- 0.6 mm after repair (p < 0.001)., Conclusion: Patients aged over 20 years with ASD I benefit from surgical repair of the defect.

The purpose of this study was to assess the risk of coronary artery bypass grafting (CABG) in the group of patients (pts) over 70 years of age and to examine results of surgical treatment in these pts. Between January 1993 to December 1999 1276 pts underwent CABG. From this group 114 consecutive pts at the age over 70 were retrospectively studied. The average age of the pts was 71.8 +/- 2.2 years (range, 70 to 79 years). Eighty nine male (78.1%) and 25 female (21.9%) pts were operated. One or more myocardial infarction had occurred in 64.0% of pts preoperatively. All the pts underwent left cardiac catheterization. The indication for surgery was significant stenosis of the left main trunk in 35 (30.7%) pts and three vessels disease in 54 (47.4%) pts. The total number of peripheral anastomoses was 274 (average 2.4 +/- 0.9 grafts per pts). In 29 cases left internal mammary artery (to left anterior descending artery) and in 245 reversed saphenous vein grafts were used. The early postoperative mortality in the group of pts at the age over 70 (10 pts--8.8%) was significantly higher than in the group of younger pts (41 of 1162 pts). The cause of death in septuagenarians was: low cardiac output syndrome (5 pts), respiratory failure (2 pts), renal insufficiency (2 pts) and cerebral stroke (1 pt). In early postoperative course the incidence of any organ insufficiency (cardiac, respiratory, renal and neurological) was higher in the group of pts over 70 years of age than in the younger pts. Seven-year probability of survival calculated from Kaplan-Meier method was 66 +/- 4%. After operation 84.5% of pts were asymptomatic, while only 5 pts were in III and IV CCS functional class. CABG in pts at the age over 70 is associated with higher operative risk and higher rate of perioperative organ failure. After surgery most pts enjoy improvement in life quality.

Background and Aims of the Study: This retrospective study evaluated late results of surgical treatment of partial anomalous pulmonary venous connection (PAPVC) concomitant with sinus venosus-type atrial septal defect (ASD) with the use of pericardial patch technique., Methods: Between 1981 and 1995, 25 consecutive patients (18 females, seven males) underwent surgical repair of PAVPC with ASD. Mean age at surgery was 37.8 +/- 13.0 (range: 16 to 62 years). All patients underwent the procedure of covering both defect and vein with pericardial patch to direct blood flow from anomalous pulmonary veins through the ASD into the left atrium. Mean follow up was 7.8 +/- 4.0 years (range: 2 to 16 years). No patients were lost to follow up., Results: There were no early deaths. One patient died 11 months after surgery from progressive heart failure. At follow up, 10 (42.7%) patients were clinically asymptomatic. One patient had clinical signs of superior vena cava (SVC) obstruction. Electrocardiography showed no abnormalities in seven (29.2%) patients. Chest radiography revealed normal pulmonary vascularity in 22 (91.7%) patients and no residual shunts were found in the SVC., Conclusion: The patch method of repair of PAPVC with sinus venosus ASD in adults with use of autologous pericardium is a safe and effective procedure.

There are controversies regarding the possibility of returning of A wave (mitral flow at left atrial contraction) after electroconversion (EC) in patients with persisting chronic atrial fibrillation in spite of successful surgical treatment of mitral valve disease. Twenty-four hours before successful EC, thereafter daily for 1 week and then on the 14th, 21st and 28th day and 6 months after EC, ECG, M-mode, two-dimensional and Doppler echocardiography were performed in 55 patients. A wave (>0.1 m/s) appeared on the 1st day in 31 patients, on the 2nd day in the next 6, on the 3rd in 5 patients, on the 4th and 5th days in 1 patient and on the 7th day in 4 patients. In 7 patients A wave did not restore. Maximum velocity of A wave increased from 0.48 +/- 0.22 to 0.86 +/- 0.28 m/s (p < 0.05) during the follow-up. In 92% of patients with A wave 24 h after EC, significant increases in stroke index from 35 +/- 12 to 47 +/- 15 ml/m2 (p < 0.04), ejection fraction from 46 +/- 9 to 55 +/- 8% (p < 0.01) and pulmonary acceleration time from 94 +/- 26 to 107 +/- 22 ms (p < 0.05) were observed. Sinus rhythm was still present on the 28th day in 34 patients (62%) and after 6 months in 31 patients (57%), all of them with A wave. observation shows the increase in pulmonary acceleration time, the decrease in the left atrial area and the increase in its systolic function in patients with A wave. Appearance of A wave determined the hemodynamic improvement, but we did not observe a correlation between maximal velocity of A wave and hemodynamic improvement. Appearance of A wave had a low predictive value for maintaining sinus rhythm (sensitivity 58% and specificity 45%). Relative increase in A wave velocity during the 1st week after EC correlated positively with long-term maintenance of sinus rhythm (r = 0.62; p < 0.001).

In many patients operated on for valvular heart diseases indications are present to digitalis administration in the preoperative period. During extracorporeal circulation fluctuations occur of blood potassium concentration which increase the risk for toxic effect of digitalis. In the work, digoxin concentration was studied in the serum of patients operated on in extracorporeal circulation in whom administration of this drug was discontinued 48 hours before the operation. The first digoxin dose (0.5 mg) was given directly after withdrawal of extracorporeal circulation, and another 0.5 mg was given after 4 hours. Digoxin concentrations were determined by fluorescence-polarization-immunological method using TD* Abbott device. The digoxin concentration increased rapidly and reached its peak after 6 hours (1.9 ng/ml), decreasing after 12 hours to 0.9 ng/ml and persisted at this therapeutic level in further samples. The present studies demonstrated that digoxin administration directly after withdrawal of extracorporeal circulation and within 24 hours after the operation in commonly accepted doses provided therapeutic concentration of the drug and caused no increase of the risk for toxic reaction development.

In 55 patients aged 47 +/- 6 years successful electrical cardioversion of atrial fibrillation was made. 24 hours before and after cardioversion, ekg and M-mode, 2-D and Doppler echocardiography was performed. Important improvement in ejection fraction (Simpson method), (p < 0.005) and in stroke index (Simpson method, p < 0.01; Doppler method, p < 0.005) was found in 64% of pts. Pts with haemodynamic improvement (HI) were significantly younger, had smaller, left atrial area in apical two-chamber view and left ventricular diastolic diameter and longer pulmonary acceleration time. In pts with HI the duration of AF was significantly shorter and closed mitral commissurotomy less frequent (p < 0.05). Restoration of mechanical atrial function (A-wave) was found in 44% of pts. In pts with A-wave HI was more often (p < 0.001). There was no correlation between maximal peak A-wave flow velocity and HI.

265 patients (168 women, 97 men) after cardiac surgery (mitral valve replacement--74 pts, mitral commissurotomy--158 pts, aortic valve replacement--6 pts, replacement of both valves--16 pts, closure of ASD--11 pts) were randomized after successful electro-conversion of atrial fibrillation to quinidine (63 pts), verapamil (56 pts), amiodarone (50 pts), digoxin (56 pts) or control group (40 pts). The groups were comparable regarding age, sex and mitral valve disease distribution, heart volume, echocardiographic left atrium size and time from cardiac surgery to electro-conversion. After one year sinus rhythm was still present in 43% receiving quinidine, 43% receiving verapamil, 40% receiving amiodarone, 22% receiving digoxin, 20% in the untreated group, and after two years in 14%, 11%, 20%, 0% and 0%--respectively. The treatment was discontinued because of side effects in 13% of pts in the quinidine group, 8% of pts in the amiodarone group and 4% of pts in the verapamil group. It is concluded that quinidine, amiodarone and verapamil compared with control group are significantly (p less than 0.05--after one year) more effective in preventing late relapses of atrial fibrillation. Digoxin is ineffective in preventing recurrence of the arrhythmia. There are no significant differences between quinidine, verapamil and amiodarone regarding its prophylactic efficacy.