Search

Implanted biomaterials are often inevitably attacked by the bacterial infection. So far this problem has not been sufficiently explained and solved. It represents an ‘evergreen’ in the artificial heart research. Infection of biomaterials is a completely new clinical entity that profoundly differs from the common clinical course of various kinds of infections and their treatment. These infections are persistent; they resist host defense mechanisms and antibiotic therapy because the nature of these microorganisms has changed due to their protection by the biofilm of some bacteria on the surfaces of implanted biomaterials. In our 66 long-term experiments with total artificial heart (TAH) in 25 animals, the infection and sepsis were the main causes of death. The different organs, attacked by the bacterial and septic complications, varied from case to case as the predominant organs, the function of which ceased to be compatible with further survival. The main foci where the infection started were also very variable. The artificial hearts used in these 25 calves were predominantly of TNS-BRNO-VII type (19 animals), TNS-BRNO-II type (4 animals) and of ROSTOCK TAH type (2 animals). The decrease of the immune defense in the TAH recipients of different intensity was evident during the course of infectious process and simultaneously, the virulence and resistance of the microorganisms against antibiotics substantially increased. The activity of the infectious agents was often combined with increased blood coagulation and thrombi formation. In 5 calves hemolytic and hemorrhagic episodes were observed, and in 15 calves without simultaneous anti-calcification treatment, a primary calcification of driving diaphragms was observed. A common dystrophic calcification sometimes complicated septic thrombogenesis. The tactics of the antibiotic therapy differed according to the results of hemocultivation tests and body temperature and was often supported by the stimulation of the immune resistance. In 2 cases we used the coating of blood chamber and driving diaphragm with albumin and hydrophilic polyurethane in order to show whether this changed surface will influence positively or negatively the bacterial seeding on the biomaterial surface. We assume the infections in the TAH recipients to be a multi-factorial process, and therefore the prevention and therapy ought to be also multi-factorial. We tried to respect this approach and we were able to increase the survival from 39 to 293 days. [Copyright &y& Elsevier]

Background: Chronic heart failure (CHF) is one of the most common causes of mortality in industrialized countries despite regular therapeutic advances. Numerous factors influence mortality in CHF patients, including nutritional status. It is known that malnutrition is a risk factor for mortality, whereas obesity may play a protective role, a phenomenon dubbed the "obesity paradox". However, the effect of the obesity-malnutrition association on mortality has not been previously studied for CHF. Our aim was to study the effect of nutritional status on overall mortality in CHF patients.Methods: This retrospective, multicenter study was based on a French nationwide database (PMSI). We included all CHF patients aged ≥18 years admitted to all public and private hospitals between 2012 and 2016 and performed a survival analysis over 1 to 4 years of follow-up.Results: Malnutrition led to a significant decrease in life expectancy in CHF patients when compared with normal nutritional status (aHR=1.16 [1.14-1.18] at one year and aHR=1.04 [1.004-1.08] at four years), obese, and obese-malnutrition groups. In contrast, obesity led to a significant increase in life expectancy compared with normal nutritional status (aHR=0.75 [0.73-0.78] at one year and aHR=0.85 [0.81-0.90] at four years), malnutrition, and obese-malnutrition groups. The mortality rate was similar in patients presenting both malnutrition and obesity and patients with normal nutritional status.Conclusions: Our results indicate that the protective effect on mortality observed in obese CHF patients seems to be linked to fat massincrease. Furthermore, malnourished obese and normal nutritional status patients had similar mortality rates. Further studies should be conducted to confirm our results and to explore the physiopathological mechanisms behind these effects. [ABSTRACT FROM AUTHOR]

Background: Early access experience in France with tafamidis meglumine, a selective transthyretin stabilizer for transthyretin-related amyloidosis cardiomyopathy (ATTR-CM), following transthyretin-related amyloidosis (ATTR) polyneuropathy approval and positive ATTR-ACT study results., Aim: To describe the characteristics and clinical outcomes for patients in the French ATTR-CM tafamidis meglumine early access programme (28 Nov 2018 to 01 Jun 2021)., Methods: Patients with confirmed ATTR-CM received tafamidis meglumine 20mg/day or 80mg/day. Demographic and clinical data were collected prospectively until patients discontinued treatment or died, or the programme ended., Results: Overall, 222 physicians from 126 centres enrolled 2788 patients. The median age was 82years, 81.6% were male and New York Heart Association severity was class I for 12.8%, class II for 60.1% and class III for 27.0%. Overall, 1943 (74.6%) had genetic testing, and the results were available at tafamidis start for 1208 (62.2%) patients: 995 (82.4%) had wild-type ATTR and 213 (17.6%) had hereditary ATTR. Most patients started treatment≤12months after diagnosis (88.3%): 2268 (81.3%) at 20mg/day, with 401 (17.7%) increasing to 80mg/day. Median follow-up duration was 11.8months. New York Heart Association class improved or remained stable for 1299 (77.6%), whereas 376 (22.4%) worsened between inclusion and last follow-up. Among patients initiated at 80mg, 297 (81.1%) improved or remained stable and 69 (18.9%) worsened. New York Heart Association class progression did not vary with age. The 18-month survival rates were 89.8% (95% confidence interval: 87.0-92.0) among patients aged<80years, and 86.5% (95% confidence interval: 83.9-88.7) among those aged≥80years., Conclusions: Early tafamidis meglumine access was given to 2788 patients with ATTR-CM. New York Heart Association class progression and survival were consistent with previously published data., (Copyright © 2024. Published by Elsevier Masson SAS.)

Background: The best management of symptomatic patients with low-gradient (LG) severe aortic stenosis (AS) and preserved left ventricular ejection fraction (LVEF) has not been established. The Randomised study for the Optimal Treatment of symptomatic patients with low-gradient severe Aortic valve Stenosis (ROTAS) trial aimed to assess the superiority of aortic valve replacement (AVR) versus medical treatment (MT) in this specific group of AS patients., Methods: Patients with symptomatic LG severe AS and preserved LVEF (>50%) underwent dobutamine stress echocardiography and/or CT-aortic calcium score to confirm AS severity and were then randomised 1:1 to AVR or MT. The primary endpoint was a composite of overall death and/or cardiovascular hospitalisation., Results: The ROTAS study was stopped early because of insufficient recruitment. In the end, only 52 patients (age 79±7 years; women 54%; NYHA III-IV 27%; median STS score 3.3%) were included in the study. During follow-up (mean: 14±7 months), the primary endpoint occurred in 12 (23%) patients. Compared with MT, AVR was not associated with a significant prognostic benefit (events: 5/26 (19%) vs 7/26 (27%) (HR 0.76, 95% CI 0.24 to 2.39, p=0.63). During follow-up, 11 (42%) patients in the MT group developed class I criteria for AVR or severe symptoms justifying a cross-over to the AVR group., Conclusions: Because of the small number of included patients and short follow-up the ROTAS trial was underpowered and unable to demonstrate a difference in the study endpoint between treatment arms. In patients in the MT arm, a regular echocardiographic and clinical assessment might be useful to disclose those developing class I indications of AVR or severe AS-related symptoms., Trial Registration Number: NCT01835028., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Aims: Based on retrospective studies, the 2022 European guidelines changed the definition of post-capillary pulmonary hypertension (pcPH) in heart failure (HF) by lowering the level of mean pulmonary artery pressure (mPAP) and pulmonary vascular resistance (PVR). However, the impact of this definition and its prognostic value has never been evaluated prospectively., Methods: Stable left HF patients with the need for right heart catheterization were enrolled from 2010 to 2018 and prospectively followed up in this multicentre study. The impact of the successive pcPH definitions on pcPH prevalence and subgroup [i.e. isolated (IpcPH) vs. combined pcPH (CpcPH)] was evaluated. Multivariable Cox regression analysis was used to assess the prognostic value of mPAP and PVR on all-cause death or hospitalization for HF (primary outcome)., Results: Included were 662 HF patients were (median age 63 years, 60% male). Lowering mPAP from 25 to 20 mmHg resulted in +10% increase in pcPH prevalence, whereas lowering PVR from 3 to 2 resulted in +60% increase in CpcPH prevalence (with significant net reclassification improvement for the primary outcome). In multivariable analysis, both mPAP and PVR remained associated with the primary outcome [hazard ratio (HR) 1.02, 95% confidence interval (CI) 1.00-1.03, P = .01; HR 1.07, 95% CI 1.00-1.14, P = .03]. The best PVR threshold associated with the primary outcome was around 2.2 WU. Using the 2022 definition, pcPH patients had worse survival compared with HF patients without pcPH (log-rank, P = .02) as well as CpcPH compared with IpcPH (log-rank, P = .003)., Conclusions: This study is the first emphasizing the impact of the new pcPH definition on CpcPH prevalence and validating the prognostic value of mPAP > 20 mmHg and PVR > 2 WU among HF patients., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Many patients with heart failure and preserved ejection fraction have no overt volume overload and normal resting left atrial (LA) pressure., Objectives: This study sought to characterize patients with normal resting LA pressure (pulmonary capillary wedge pressure [PCWP] <15 mm Hg) but exercise-induced left atrial hypertension (EILAH)., Methods: The REDUCE LAP-HF II (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure) trial randomized 626 patients with ejection fraction ≥40% and exercise PCWP ≥25 mm Hg to atrial shunt or sham procedure. The primary trial outcome, a hierarchical composite of death, heart failure hospitalization, intensification of diuretics, and change in health status was compared between patients with EILAH and those with heart failure and resting left atrial hypertension (RELAH)., Results: Patients with EILAH (29%) had similar symptom severity, but lower natriuretic peptide levels, higher 6-minute walk distance, less atrial fibrillation, lower left ventricular mass, smaller LA volumes, lower E/e', and better LA strain. PCWP was lower at rest, but had a larger increase with exercise in EILAH. Neither group as a whole had a significant effect from shunt therapy vs sham. Patients with EILAH were more likely to have characteristics associated with atrial shunt responsiveness (peak exercise pulmonary vascular resistance <1.74 WU) and no pacemaker (63% vs 46%; P < 0.001). The win ratio for the primary outcome was 1.56 (P = 0.08) in patients with EILAH and 1.51 (P = 0.04) in those with RELAH when responder characteristics were present., Conclusions: Patients with EILAH had similar symptom severity but less advanced myocardial and pulmonary vascular disease. This important subgroup may be difficult to diagnose without invasive exercise hemodynamics, but it has characteristics associated with favorable response to atrial shunt therapy. (A Study to Evaluate the Corvia Medical, Inc. IASD System II to Reduce Elevated Left Atrial Pressure in Patients With Heart Failure [REDUCE LAP-HF TRIAL II]; NCT03088033)., Competing Interests: Funding Support and Author Disclosures This study was sponsored by Corvia Medical Inc. Dr Litwin has received research funding from the department of Veterans Affairs, Corvia, AstraZeneca, V-Wave, Axon Therapeutics, and Eli Lilly all paid to the institution; has received consulting fees from CVRx, Axon Therapeutics, Occlutech, Eli Lilly, and Rivus Pharmaceuticals; and has received travel grants, speaker fees, and advisory board honoraria from NovoNordisk and Roche. Dr Komtebedde is employed by Corvia. Dr Burkhoff has consulted for Corvia. Dr Hasenfuß has consulted for AstraZeneca, Boehringer Ingelheim, Corvia, Impulse Dynamics, Novartis, Servier, Vifor; has received honoraria for lectures from AstraZeneca, Bayer, Impulse Dynamics, Novartis, Pfizer, Servier, and Vifor; and is a co-principal investigator to Impulse Dynamics. Dr Borlaug has received research grants from Corvia, AstraZeneca, Medtronic, GlaxoSmithKline, Mesoblast, Novartis, and Tenax Therapeutics; and has received consulting fees from Actelion, Amgen, Aria, Axon Therapies, Boehringer Ingelheim, Edwards Lifesciences, Eli Lilly, Imbria, Janssen, Merck, Novo Nordisk, and VADovations. Dr Solomon has received research grants from Alnylam, AstraZeneca, Bellerophon, Bayer, Bristol Myers Squibb, Cytokinetics, Eidos, GlaxoSmithKline, Ionis, Lilly, MyoKardia, the National Institutes of Health/National Heart, Lung, and Blood Institute, Novartis, Novo Nordisk, Respicardia, Sanofi Pasteur, Theracos, US2.AI; and has consulted for Abbott, Action, Akros, Alnylam, Amgen, Arena, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardior, Cardurion, Corvia, Cytokinetics, Daiichi-Sankyo, GlaxoSmithKline, Lilly, Merck, Myokardia, Novartis, Roche, Theracos, Quantum Genomics, Cardurion, Janssen, Cardiac Dimensions, Tenaya, Sanofi-Pasteur, DiNAQOR, Tremeau, CellProthera, Moderna, American Regent, Sarepta, Lexicon, AnaCardio, and Akros. Dr Mohan has received research support from Corvia and V-Wave paid to the institution. Dr Kahwash has served as a consultant for Medtronic, Impulse Dynamics, and Cardionomic. Dr Sverdlov has received research grants from the National Heart Foundation of Australia (Future Leader Fellowships 101918 and 106025), Department of Health and Aged Care (Australia): Medical Research Future Fund (MRF2017053), New South Wales Health (Australia), Novartis Australia, Biotronik, RACE Oncology, Bristol Myers Squibb, Roche Diagnostics, and Vifor Pharma; and has received personal fees from Novartis, Bayer, Bristol Myers Squibb, AstraZeneca, Corvia, and Boehringer Ingelheim. Dr Fail has received research support paid to the institution from Corvia and Alleviant. Dr Chung has served as a consultant to Intershunt. Dr Kaye has received research support from Corvia. Dr Hummel has received research grant funding from National Institutes of Health, Veterans Affairs, American Heart Association, Novartis, Pfizer, AstraZeneca, Corvia, and Axon Therapies. Dr Zirlik has received personal consulting fees and honoraria for lectures from Abbott, Abiomed, AstraZeneca, Amarin, Amgen, Bayer Healthcare, Biotronik, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimensions, Cardiorentis, Corvia, Daichi Sankyo, Edwards Lifesciences, Eli Lilly, Janssen, Merck, Neucomed, Novo Nordisk, Novartis, Rigel, and Stealth Peptides. Dr Hayward has received research support from Corvia, Medtronic, Abbott, Roche, and Procyrion. Dr Lewis has received research funding from the National Institutes of Health (R01-HL 151841, R01-HL131029, R01-HL159514), American Heart Association (15GPSGC-24800006), Amgen, Cytokinetics, Applied Therapeutics, AstraZeneca, and SoniVie; has received honoraria for advisory boards outside of the current study from Pfizer, Merck, Boehringer Ingelheim, NXT, American Regent, Cyclerion, Cytokinetics, and Amgen; and has received royalties from UpToDate for scientific content authorship related to exercise physiology. Dr Gupta has received research support from the National Institutes of Health, Imara, Corvia, and Astellas Pharma. Dr Cikes has received institutional research grants from Abbott, Novartis, and Pfizer; has received travel grants, speaker fees, and advisory board honoraria from Abbott, Abiomed, Amicus, AstraZeneca, Bayer, Boehringer Ingelheim, GE Healthcare, Krka Pharma, LivaNova, Medtronic, Novartis, Orion Corporation, Pfizer, Sanofi, Swixx BioPharma, and Teva Pharmaceutical Industries, all outside of the present study; and has received research support from Corvia. Dr Gustafsson has received honoraria outside the present study as a consultant for Abbott, Pfizer, Ionis Pharmaceuticals, Bayer, AstraZeneca, and Alnylam; has received speaker fees from Novartis and Orion Pharma; and has received research support from Corvia. Dr Silvestry has received research support from Corvia. Dr Rowin has received research support from Corvia; and has served as a consultant for Cardiovascular Clinical Sciences. Dr Cutlip has received research support from Corvia paid to the institution. Dr Kitzman has received honoraria outside the present study as a consultant for Boehringer Ingelheim, Novo Nordisk, AstraZeneca, Rivus, Keyto, and Novartis; has received grant funding outside the present study from Novartis, Bayer, Novo Nordisk, and AstraZeneca; owns stock in Gilead Sciences; and has received research support from Corvia. Dr Shah has received research grants from the National Institutes of Health (U54 HL160273, R01 HL107577, R01 HL127028, R01 HL140731, R01 HL149423), Actelion, AstraZeneca, Corvia, Novartis, and Pfizer; and has received personal fees from Abbott, Actelion, AstraZeneca, Amgen, Aria CV, Axon Therapies, Bayer, Boehringer Ingelheim, Boston Scientific, Bristol Myers Squibb, Cardiora, Coridea, CVRx, Cyclerion, Cytokinetics, Edwards Lifesciences, Eidos, Eisai, Imara, Impulse Dynamics, Intellia Therapeutics, Ionis, Ironwood, Lilly, Merck, MyoKardia, Novartis, Novo Nordisk, Pfizer, Prothena, Regeneron, Rivus, Sanofi, Shifamed, Tenax, Tenaya, and United Therapeutics. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Heart failure- (HF) and arrhythmia-related complications are the main causes of morbidity and mortality in patients with nonischemic dilated cardiomyopathy (NIDCM). Cardiovascular magnetic resonance (CMR) imaging is a noninvasive tool for risk stratification based on fibrosis assessment. Diffuse interstitial fibrosis in NIDCM may be a limitation for fibrosis assessment through late gadolinium enhancement (LGE), which might be overcome through quantitative T1 and extracellular volume (ECV) assessment. T1 and ECV prognostic value for arrhythmia-related events remain poorly investigated. We asked whether T1 and ECV have a prognostic value in NIDCM patients., Methods: This prospective multicenter study analyzed 225 patients with NIDCM confirmed by CMR who were followed up for 2 years. CMR evaluation included LGE, native T1 mapping and ECV values. The primary endpoint was the occurrence of a major adverse cardiovascular event (MACE) which was divided in two groups: HF-related events and arrhythmia-related events. Optimal cutoffs for prediction of MACE occurrence were calculated for all CMR quantitative values., Results: Fifty-eight patients (26%) developed a MACE during follow-up, 42 patients (19%) with HF-related events and 16 patients (7%) arrhythmia-related events. T1 Z-score (p = 0.008) and global ECV (p = 0.001) were associated with HF-related events occurrence, in addition to left ventricular ejection fraction (p < 0.001). ECV > 32.1% (optimal cutoff) remained the only CMR independent predictor of HF-related events occurrence (HR 2.15 [1.14-4.07], p = 0.018). In the arrhythmia-related events group, patients had increased native T1 Z-score and ECV values, with both T1 Z-score > 4.2 and ECV > 30.5% (optimal cutoffs) being independent predictors of arrhythmia-related events occurrence (respectively, HR 2.86 [1.06-7.68], p = 0.037 and HR 2.72 [1.01-7.36], p = 0.049)., Conclusions: ECV was the sole independent predictive factor for both HF- and arrhythmia-related events in NIDCM patients. Native T1 was also an independent predictor in arrhythmia-related events occurrence. The addition of ECV and more importantly native T1 in the decision-making algorithm may improve arrhythmia risk stratification in NIDCM patients. Trial registration NCT02352129. Registered 2nd February 2015-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02352129., (© 2023. The Author(s).)

Background: High-output heart failure is a rare condition that occurs when the heart is unable to respond to a sustained increase in blood demand. On echocardiography, a cardiac index of > 4 L/min/m 2 (or 6 L/min) is a clear indicator of this disorder. The causes of high-output heart failure vary, but they all involve peripheral vasodilation or arteriovenous shunting. Renal cell carcinoma is well known for producing high levels of angiogenic growth factors that induce arteriovenous shunts. The decrease in peripheral arterial resistance and the increase in venous return result in a permanent high cardiac output, followed by congestive heart failure. Single bone metastases of renal clear cell carcinoma tumours causing high cardiac output and heart failure symptoms have been reported less than ten times in the medical literature., Case Presentation: Before a right-shoulder painful lump with a murmur when auscultated, magnetic resonance imaging revealed a large scapular mass, which was biopsied and found to be a bone metastasis of renal cell carcinoma. Two months later, the patient developed heart failure for the first time. There was no evidence of cardiac disease on echocardiography. The cardiac output was 9.8 L/min and the cardiac index was 5.1 L/min/m 2 . Doppler ultrasound revealed numerous arteriovenous shunts in the large scapular metastasis and a right axillary artery flow of 24% of cardiac output. Sustained lower cardiac output was obtained following lesion-focused radiotherapy and systemic antiangiogenic treatment with axitinib and pembrolizumab., Conclusions: Herein, we present a unique case of high-output heart failure in a 70-year-old man diagnosed by echocardiography and upper-limb Doppler ultrasound in the context of metastatic renal cell carcinoma without pre-existing cardiac disease. We stress the potentially life-threatening hemodynamic consequences of hypervascularity associated with arteriovenous shunts within a single metastatic renal cell carcinoma implant, the importance of auscultating any progressing bone mass, and the utility of non-invasive Doppler ultrasound assessment in this setting., (© 2022. The Author(s).)

Aims: Defining the risk of atrial fibrillation (AF) in hypertrophic cardiomyopathy (HCM) patients is an important clinical and prognostic challenge. The aim of this study is to determine HCM phenogroups with different risk of AF occurrence at 5 years., Methods and Results: We applied retrospectively the Bayesian method, which can analyze a large number of variables, to differentiate phenogroups of patients with different risks of AF and prognoses across a French prospective on-going hospital-based registry of adult HCM patients (REMY). Clinical and imaging data were prospectively recorded, and patients were followed for 5 years. A total of 1431 HCM patients were recruited, including 1275 analyzed in the present study after exclusion criteria. The population included 412 women, 369 patients with obstructive HCM, and 252 implanted with an ICD. AF occurred in 167 (11.6%) patients during the 5 year follow-up. Three phenogroups were defined according to their common clinical and echocardiographic characteristics. Patients at the highest risk were oldest, more often female, with more frequent comorbidities, anteroposterior diameter of the left atrium was significantly greater, with diastolic dysfunction, outflow-tract obstruction, and mitral valve abnormality, and presented higher pulmonary artery pressure and/or right-ventricular dysfunction. These also had a higher risk of all-cause hospitalizations and death., Conclusion: Based on a clustering analysis, three phenogroups of HCM according to the risk of AF occurrence can be identified. It can indicate which patients should be more monitored and/or treated, particular to prevent the risk of stroke., (© 2021. Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Diagnostic and patients' management modifications induced by whole-body 18F-FDG-PET/CT had not been evaluated so far in prosthetic valve (PV) or native valve (NV) infective endocarditis (IE)-suspected patients., Methods: In sum, 140 consecutive patients in 8 tertiary care hospitals underwent 18F-FDG-PET/CT. ESC-2015-modified Duke criteria and patients' management plan were established jointly by 2 experts before 18F-FDG-PET/CT. The same experts reestablished Duke classification and patients' management plan immediately after qualitative interpretation of 18F-FDG-PET/CT. A 6-month final Duke classification was established., Results: Among the 70 PV and 70 NV patients, 34 and 46 were classified as definite IE before 18F-FDG-PET/CT. Abnormal perivalvular 18F-FDG uptake was recorded in 67.2% PV and 24.3% NV patients respectively (P < .001) and extracardiac uptake in 44.3% PV and 51.4% NV patients. IE classification was modified in 24.3% and 5.7% patients (P = .005) (net reclassification index 20% and 4.3%). Patients' managements were modified in 21.4% PV and 31.4% NV patients (P = .25). It was mainly due to perivalvular uptake in PV patients and to extra-cardiac uptake in NV patients and consisted in surgery plan modifications in 7 patients, antibiotic plan modifications in 22 patients and both in 5 patients. Altogether, 18F-FDG-PET/CT modified classification and/or care in 40% of the patients (95% confidence interval: 32-48), which was most likely to occur in those with a noncontributing echocardiography (P < .001) or IE classified as possible at baseline (P = .04), while there was no difference between NV and PV., Conclusions: Systematic 18F-FDG-PET/CT did significantly and appropriately impact diagnostic classification and/or IE management in PV and NV-IE suspected patients., Clinical Trials Registration: NCT02287792., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aims: Tricuspid regurgitation (TR) was long forgotten until recent studies alerting on its prognostic impact. Cardiac output (CO) is the main objective of heart mechanics. We sought to compare clinical and echocardiographic data of patients with TR from inclusion to 1-year follow-up according to initial CO., Methods and Results: Patients with isolated secondary TR and left ventricular ejection fraction (LVEF) ≥40% were prospectively included. All patients had a clinical and echocardiographic evaluation at baseline and after 1 year. Echocardiographic measurements were centralized. The patients were partitioned according to their CO at baseline. The primary outcome was all-cause death. Ninety-five patients completed their follow-up. The majority of patients had normal CO (n = 64, 67.4%), whereas 16 (16.8%) patients had low-CO and 12 (12.6%) had high-CO. right ventricular function was worse in the low-CO group but with improvement at 1 year (30% increase in tricuspid annular plane systolic excursion). LVEF and global longitudinal strain were significantly worse in the low-CO group. Overall, 18 (19%) patients died during follow-up, of which 10 (55%) patients had abnormal CO. There was a U-shaped association between CO and mortality. Normal CO patients had significantly better survival (87.5% vs. 62.5% and 66.67%) in the low- and high-CO groups, respectively, even after adjustment (heart rate 2.23 for the low-CO group and 9.08 for high-CO group; P = 0.0174)., Conclusion: Significant isolated secondary TR was associated with 19% of mortality. It is also associated with higher long-term mortality if CO is abnormal, suggesting a possible role for evaluating better and selecting patients for intervention., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Few data exist concerning genotype-phenotype relationships in left ventricular noncompaction (LVNC)., Methods and Results: From a multicenter French Registry, we report the genetic and clinical spectrum of 95 patients with LVNC, and their genotype-phenotype relationship. Among the 95 LVNC, 45 had at least 1 mutation, including 14 cases of mutation in ion channel genes. In a complementary analysis including 16 additional patients with ion channel gene mutations, for a total of 30 patients with ion channel gene mutation, we found that those patients had higher median LV ejection fraction (60% vs 40%; P < .001) and more biventricular noncompaction (53.1% vs 18.5%; P < .001) than the 81 other patients with LVNC. Among them, both the 19 patients with an HCN4 mutation and the 11 patients with an RYR2 mutation presented with a higher LV ejection fraction and more frequent biventricular noncompaction than the 81 patients with LVNC but with no mutation in the ion channel gene, but only patients with HCN4 mutation presented with a lower heart rate., Conclusions: Ion channel gene mutations should be searched systematically in patients with LVNC associated with either bradycardia or biventricular noncompaction, particularly when LV systolic function is preserved. Identifying causative mutations is of utmost importance for genetic counselling of at-risk relatives of patients affected by LVNC., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Left ventricular non-compaction (LVNC) is a cardiomyopathy that may be of genetic origin; however, few data are available about the yield of mutation, the spectrum of genes and allelic variations. The aim of this study was to better characterize the genetic spectrum of isolated LVNC in a prospective cohort of 95 unrelated adult patients through the molecular investigation of 107 genes involved in cardiomyopathies and arrhythmias. Fifty-two pathogenic or probably pathogenic variants were identified in 40 patients (42%) including 31 patients (32.5%) with single variant and 9 patients with complex genotypes (9.5%). Mutated patients tended to have younger age at diagnosis than patients with no identified mutation. The most prevalent genes were TTN, then HCN4, MYH7, and RYR2. The distribution includes 13 genes previously reported in LVNC and 10 additional candidate genes. Our results show that LVNC is basically a genetic disease and support genetic counseling and cardiac screening in relatives. There is a large genetic heterogeneity, with predominant TTN null mutations and frequent complex genotypes. The gene spectrum is close to the one observed in dilated cardiomyopathy but with specific genes such as HCN4. We also identified new candidate genes that could be involved in this sub-phenotype of cardiomyopathy., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Pulmonary hypertension (PH) is a common and severe complication of heart failure (HF). Consequently, HF is the leading cause of PH. For many years, specialists have attempted to better understand the pathophysiology of PH in HF, to define its prevalence and its impact on prognosis in order to improve the therapeutic management of these patients. Nowadays, despite the recent guidelines published on the subject, several points remain unclear or debated, and until now, no study has demonstrated the efficacy of any treatment. The aim of this review is to report the evolution of the concepts on post-capillary PH (diagnosis, prevalence, prognosis, and therapeutics). The main issues are raised, focusing especially on the link between structural alterations and haemodynamic abnormalities, to discuss the possible reasons for treatment failures and future potential targets., (© 2018 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.)

Aims: Mutations in PRKAG2, the gene encoding for the γ2 subunit of 5'-AMP-activated protein kinase (AMPK), are responsible for an autosomal dominant glycogenosis with a cardiac presentation, associating hypertrophic cardiomyopathy (HCM), ventricular pre-excitation (VPE), and progressive heart block. The aim of this study was to perform a retrospective time-to-event study of the clinical manifestations associated with PRKAG2 mutations., Methods and Results: A cohort of 34 patients from 9 families was recruited between 2001 and 2010. DNA were sequenced on all exons and flanking sequences of the PRKAG2 gene using Sanger sequencing. Overall, four families carried the recurrent p.Arg302Gln mutation, and the five others carried private mutations among which three had never been reported. In the total cohort, at 40 years of age, the risk of developing HCM was 61%, VPE 70%, conduction block 22%, and sudden cardiac death (SCD) 20%. The global survival at 60 years of age was 66%. Thirty-two per cent of patients (N = 10) required a device implantation (5 pacemakers and 5 defibrillators) at a median age of 66 years, and two patients required heart transplant. Only one patient presented with significant skeletal muscle symptoms. No significant differences regarding the occurrence of VPE, ablation complications, or death incidence were observed between different mutations., Conclusion: This study of patients with PRKAG2 mutations provides a more comprehensive view of the natural history of this disease and demonstrates a high risk of cardiac complications. Early recognition of this disease appears important to allow an appropriate management., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.)

Objective: To confirm that electrical myostimulation is a good alternative to conventional aerobic training in patients with chronic heart failure and to compare the effects of both training programmes in patients with different exercise capacities., Patients and Methods: A total of 44 patients with stable chronic heart failure underwent 5 weeks of exercise training, with electrical myostimulation or conventional aerobic training programmes. At baseline and after the training period, patients performed a symptom-limited cardiopulmonary exercise test and a 6-min walk test., Results: Oxygen uptake at the end of exercise (V.O2 peak) and at ventilatory threshold (V.O2 VT) increased after electrical myostimulation (p< 0.001) and conventional aerobic training (p< 0.001) training programmes. The slope of the relationship between V.O2 and workload was reduced after electrical myostimulation (p< 0.05), but not after conventional aerobic training. Recovery was improved after both training programmes (p< 0.05), and the distance walked in 6 min was increased (p< 0.001). These improvements were not statistically different between electrical myostimulation and conventional aerobic training. Moreover, electrical myostimulation induced greater improvements in patients with low exercise capacity, whereas conventional aerobic training induced improved performance in patients with average exercise capacity., Conclusion: Five weeks of electrical myostimulation and conventional aerobic training exercise training produced similar improvements in exercise capacity in patients with chronic heart failure. However, electrical myostimulation appears to be more effective in patients with low exercise capacity than in those with average exercise capacity.

Acute renal failure due to paradoxical embolism is exceptionally reported. A new case gives the opportunity to review mechanisms, diagnosis and therapeutic issues. A 49-year-old woman without medical history is admitted for crural venous thrombosis and acute pulmonary embolism. At day 2, a left flank acute pain with fever, doubling of plasma creatinine, and controlateral recurrence at day 12, leads to diagnosis of acute bilateral renal infarction only at day 20. Paradoxical embolism is then suspected and confirmed by transoesophageal contrast echocardiography, disclosing patent foramen ovale with right-to-left shunt. Nine months later, successful percutaneous closure of patent foramen ovale with Amplatzer PFO occluder 25 mm allows subsequent discontinuation of oral anticoagulation. Diagnostic criteria for paradoxical embolism are present in our case. If this mechanism is often discussed in cryptogenic cerebrovascular stroke of young patients, it is exceptionally reported as responsible for clinical renal disease, particularly acute renal failure (whereas anatomical renal involvement is not unfrequent). The clue is the difficulty to suspect and confirm renal infarction, especially when classical causes of cardiac embolism are lacking. The relevance is the opportunity to save renal tissue in the acute phase, and to close patent foramen ovale (currently most often percutaneously) weeks or months after the acute bout.

Background and Aim of the Study: Although described in a number of necropsy studies, endocarditis on mitral annular calcification (MAC) has rarely been reported during life. The study aim was to assess the frequency and specific features of bacterial endocarditis complicating MAC., Methods: Data relating to 62 cases of infective endocarditis of the native mitral valve diagnosed with multiplane transesophageal echocardiography (TEE) over a five-year period were collected prospectively., Results: Among 62 patients, 15 (24%) had vegetations originating from a calcified mitral annulus (group 1), while 47 had classic leaflet endocarditis (group 2). Group 1 patients differed significantly from group 2 patients with regard to: (i) higher incidence of diabetes mellitus and cancers; (ii) initial clinical presentation, with febrile coma or meningoencephalitis in 53% of cases; (iii) echocardiographic features, with significantly greater vegetations, presence of calcium-dense echoes within the vegetation, high frequency of ring abscess, and high frequency of para-annular ventriculoatrial leakage; and (iv) poorer clinical outcome, with 53% in-hospital mortality., Conclusion: MAC appears to be an underestimated predisposing factor for a particularly severe type of bacterial endocarditis. The use of multiplane TEE should improve current knowledge of this disease.

Most often revealed thanks to chest pain, acute aortic dissection must be suspected and diagnosed without losing anytime, because of their evolutive risks and their specific treatment in a specialised unit. Once the early management is over, survivers must be closely followed, specially for their blood pressure to be kept normal, and to screen for secondary complications that would require surgery. Owing to the improvement of early management and follow up, facilitated by the new non-invasive imaging techniques of the aorta, the severe prognosis of this disease has significantly improved.