[Cardiology: what's new in 2023]. / Cardiologie: ce qui a changé en 2023.

The year 2023 has been extremely rich in new publications in the various subfields of cardiology. Furthermore, the European Society of Cardiology (ESC) has issued revised guidelines focused on the management of acute coronary syndrome (ACS) and endocarditis, as well as an update on the recommendations for the management of heart failure and cardiovascular prevention. The most significant updates according to the Cardiology Department of CHUV are summarized in this review article.

L'année 2023 a été extrêmement riche en nouvelles publications dans les différents sous-domaines de la cardiologie. De plus, la Société européenne de cardiologie (ESC) a formulé des directives révisées axées sur le management du syndrome coronarien aigu (SCA) et de l'endocardite ainsi qu'une mise à jour des recommandations sur la prise en charge de l'insuffisance cardiaque et la prévention cardiovasculaire. Les nouveautés les plus importantes selon l'équipe du Service de cardiologie du CHUV sont résumées dans cet article de synthèse.

Pulmonary Hypertension in Left Heart Diseases: Pathophysiology, Hemodynamic Assessment and Therapeutic Management.

Pulmonary hypertension (PH) associated with left heart diseases (PH-LHD), also termed group 2 PH, represents the most common form of PH. It develops through the passive backward transmission of elevated left heart pressures in the setting of heart failure, either with preserved (HFpEF) or reduced (HFrEF) ejection fraction, which increases the pulsatile afterload of the right ventricle (RV) by reducing pulmonary artery (PA) compliance. In a subset of patients, progressive remodeling of the pulmonary circulation resulted in a pre-capillary phenotype of PH, with elevated pulmonary vascular resistance (PVR) further increasing the RV afterload, eventually leading to RV-PA uncoupling and RV failure. The primary therapeutic objective in PH-LHD is to reduce left-sided pressures through the appropriate use of diuretics and guideline-directed medical therapies for heart failure. When pulmonary vascular remodeling is established, targeted therapies aiming to reduce PVR are theoretically appealing. So far, such targeted therapies have mostly failed to show significant positive effects in patients with PH-LHD, in contrast to their proven efficacy in other forms of pre-capillary PH. Whether such therapies may benefit some specific subgroups of patients (HFrEF, HFpEF) with specific hemodynamic phenotypes (post- or pre-capillary PH) and various degrees of RV dysfunction still needs to be addressed.

Complement blockade with eculizumab to treat acute symptomatic humoral rejection after heart transplantation.

Antibody-mediated rejection (AMR) is a major barrier preventing successful discordant organ xenotransplantation, but it also occurs in allotransplantation due to anti-HLA antibodies. Symptomatic acute AMR is rare after heart allograft but carries a high risk of mortality, especially >1 year after transplant. As complement activation may play a major role in mediating tissue injury in acute AMR, drugs blocking the terminal complement cascade like eculizumab may be useful, particularly since "standards of care" like plasmapheresis are not based on strong evidence. Eculizumab was successfully used to treat early acute kidney AMR, a typical condition of "active AMR," but showed mitigated results in late AMR, where "chronic active" lesions are more prevalent. Here, we report the case of a heart recipient who presented with acute heart failure due to late acute AMR with eight de novo donor-specific anti-HLA antibodies (DSA), and who fully recovered allograft function and completely cleared DSA following plasmapheresis-free upfront eculizumab administration in addition to thymoglobulin, intravenous immunoglobulins (IVIG), and rituximab. Several clinical (acute onset, abrupt and severe loss of graft function), biological (sudden high-level production of DSA), and pathological features (microvascular injury, C4d deposits) of this cardiac recipient are shared with early kidney AMR and may indicate a strong role of complement in the pathogenesis of acute graft injury that may respond to drugs like eculizumab. Terminal complement blockade should be further explored to treat acute AMR in recipients of heart allografts and possibly also in recipients of discordant xenografts in the future.

Comparison of Risk Stratification Scores in Pulmonary Arterial Hypertension: A Monocentric Retrospective Study at Lausanne University Hospital.

BACKGROUND: Risk assessment is the cornerstone of pulmonary arterial hypertension (PAH) management. Risk stratification scores predict prognosis and help individualize treatment. OBJECTIVES: The aims of the study include the following: (1) to compare the prediction for transplant-free survival (TFs) of 3 risk assessment tools at 3 and 5 years after diagnosis and (2) to analyze whether the initial risk stratification was altered after 1 year of treatment. METHOD: We collected retrospectively data of 50 patients diagnosed with PAH Group 1. We categorized them as low, intermediate, and high mortality risk at baseline and at 1 year with the (1) Registry to Evaluate Early and Long-Term PAH Disease Management (REVEAL) risk score version 2.0, (2) Swedish/Comparative Prospective Registry of Newly Initiated Therapies for Pulmonary Hypertension (PH) (COMPERA) score, and (3) French PH Network Registry (FPHR) score. RESULTS: TFs at 3 years is predicted by the 3 scores computed at baseline with an area under the curve (AUC) of 0.73, 0.73, and 0.77, respectively. The predictive value increased when the scores were calculated after 1 year of treatment (AUC = 0.91, 0.89, and 0.78). The prediction of TFs at 5 years was better evaluated by the COMPERA and FPHR (AUC = 0.85) than by REVEAL 2.0 (AUC = 0.69) computed at baseline. A low risk status was associated with excellent TFs whatever the scoring used. CONCLUSION: In accordance with the original publications, the 3 scores are able to predict survival up to 5 years after diagnosis. The better performance of the scores after 1 year is a further evidence for their clinical use and an indirect proof for treatment efficacy.

[Practical considerations in the use of SGLT2 inhibitors in cardiovascular diseases]. / Considérations pratiques pour l'utilisation des inhibiteurs du SGLT2 dans les maladies cardiovasculaires.

Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a class of drugs which offer cardiovascular (CV) and renal benefits. They are currently indicated as first-line treatments of type 2 diabetes mellitus (T2DM) in patients with CV disease, high CV risk, renal disease, or heart failure with reduced ejection fraction (HFrEF). Two randomized clinical trials have shown the benefits of dapagliflozin and empagliflozin in patients with HFrEF, regardless of the presence of T2DM. Despite an overall favorable safety profile, attention has to be paid to adverse events, such as an increased risk of euglycemic diabetic ketoacidosis and genital mycotic infections. We present an up-to-date narrative literature review of the physiological mechanisms of action, current indications, and side effects of SGLT2 inhibitors.

Les inhibiteurs du cotransporteur sodium-glucose de type 2 (iSGLT2) sont une classe d'antidiabétiques oraux ayant de nombreux bénéfices cardiovasculaires (CV) et rénaux. Ils sont indiqués chez les patients avec un diabète de type 2 (DT2) et une maladie CV, un risque CV élevé, une insuffisance rénale chronique ou une insuffisance cardiaque à fraction d'éjection réduite (ICFER). Des essais cliniques randomisés ont montré les bénéfices de la dapagliflozine et de l'empagliflozine chez les patients avec une ICFER, avec ou sans DT2. Malgré un profil de sécurité favorable, il convient de connaître les effets indésirables éventuels, tels que l'acidocétose euglycémique et les infections génito-urinaires. Nous présentons une revue narrative de la littérature à jour portant sur les mécanismes d'action, indications et effets secondaires des iSGLT2.

The role of Heart Failure Team in managing Mechanical Circulatory Support in a Swiss low-volume institution.

BACKGROUND: Outcomes after VAD implantation may be dependent on institutional procedural volume. Specifically, it is claimed that high volumes are associated to better clinical results. This study aims to determine if this procedure is safe even in low-volume center. METHODS: Single center, retrospective cohort study, including Heart Failure consecutive patients who received long-term VAD from 2007 to 2017. Primary outcome was survival to transplant or ongoing MCS at 1-year. Survival analysis was performed using Kaplan-Meier method. RESULTS: Data concerning 50 adult patients were examined; 35 male (70%), mean age 49+/- 8 years. VAD was implanted as BTT in 48 and DT in 2. Devices implanted were: HeartMate II in 18 (36%), HeartWare in 20 (40%), HeartMate III in 12 (24%). Outcomes were: Death in 16 (32%), heart transplant in 24 (48%), uneventful ongoing support 10 (20%). Data were analysed according to pre and post-heart team creation and 2 groups of 25 patients were identified: 2007-2013 (mean INTERMACS level 3.1) and 2014-2017 (mean INTERMACS level 3.9) showing 1-year survival of 56% and 80% respectively. According to the type of device implanted, 3 groups were identified: HMII = 18 (mean INT. level 2.7), HW=20 (mean INT. level 3.3) and HMIII=12 (mean INT. level 3.7), showing survival of 52%, 78% and 91% respectively. CONCLUSIONS: Long term MCS can be implanted at low-volume centers with survival rate not inferior to high volume centers. A Heart team specifically trained in heart failure is probably more important than institutional volume in determining outcomes after VAD implantation.

[Therapeutic options in advanced heart failure : place of durable left ventricular assist device (LVAD)]. / Options thérapeutiquesdans l'insuffisance cardiaque avancée : place de l'assistance ventriculaire gauche permanente (LVAD).

Despite the benefit of the drugs acting on neuro-humoral activation and cardiac resynchronization therapy, some patients will end in a severe refractory form of heart failure: advanced heart failure. The only therapeutic options with a positive impact on mortality and quality of life are heart transplantation and permanent left ventricular assist device (LVAD). The significant technological improvements of the past 20 years lead to a reduction of the complications associated with these devices, which now allow their use not only during the waiting period preceding heart transplantation (bridge to transplant), but also as a durable therapeutic option (destination therapy).

Malgré le bénéfice des médicaments agissant sur l'activation neuro-humorale et de la thérapie de resynchronisation, certains patients vont évoluer vers une forme sévère et réfractaire d'insuffisance cardiaque : l'insuffisance cardiaque avancée (ICA). Les seules options thérapeutiques de l'ICA ayant démontré un impact favorable sur la survie et la qualité de vie sont la transplantation cardiaque et l'implantation d'un dispositif d'assistance ventriculaire gauche permanent (LVAD, Left Ventricular Assist Device). Les importantes améliorations technologiques des vingt dernières années ont permis de réduire significativement les complications associées à ces dispositifs, permettant non seulement leur utilisation dans l'attente du greffe cardiaque (bridge to transplant), mais aussi comme option thérapeutique définitive (destination therapy).

[Cardiology update 2017]. / Cardiologie.

As usual, numerous papers published in 2017 contributed to optimize the management of patients in all clinical cardiologic fields. It is of course impossible to summarize them all in such an article. Subjects and papers were thus selected if they were thought to be particularly important for non-cardiologist physicians, especially general practitioners. The authors would also like to take the opportunity of this article to honor the memory of Pr Daniel Wagner who unfortunately passed away after less than six months at the head of our Cardiology Department. He was well recognized for his generosity as well as his clinical and scientific competence. This article is dedicated to him.

Comme à l'accoutumée, l'année 2017 a été marquée par la publication de nombreux travaux permettant d'optimaliser la prise en charge de nos patients dans tous les domaines de la cardiologie et il est évidemment impossible de les synthétiser ici de façon exhaustive. Nous avons donc sélectionné les sujets et les travaux qui nous ont paru les plus saillants et surtout les plus utiles pour nos collègues non cardiologues et particulièrement pour nos collègues médecins de premier recours. Cette revue de l'année 2017 ne serait toutefois pas complète sans un hommage au Pr Daniel Wagner qui a débuté son activité de chef du service de cardiologie du CHUV au 1er janvier et nous a quittés après seulement quelques mois passés parmi nous. Daniel fut un chef de service apprécié tant pour ses qualités humaines que pour ses compétences scientifiques et cliniques. Cet article lui est donc dédié.

[Hepatopulmonary syndrome and portopulmonary hypertension]. / Syndrome hépato-pulmonaire et hypertension porto-pulmonaire.

Hepatopulmonary syndrome (HPS) and portopulmonary hypertension (POPH) are two frequent pulmonary complications of liver disease. Portal hypertension is a key element in the pathogenesis of both disorders, which are however distinct in terms of pathogenesis, diagnosis and treatment. HPS corresponds to an abnormal arterial oxygenation in relation with the development of intrapulmonary vascular dilatations. POPH is a pulmonary arterial hypertension in the setting of portal hypertension and elevated pulmonary vascular resistance. As both diseases are associated with an increased risk of morbidity and mortality, it is important to screen and evaluate the severity of these two disorders particularly in liver transplant candidates.

Le syndrome hépato-pulmonaire (SHP) et l'hypertension porto-pulmonaire (HPP) sont deux complications pulmonaires fréquentes de la maladie hépatique. La présence d'une hypertension portale est un élément crucial dans la pathogenèse de ces deux maladies, toutefois distinctes en termes de physiopathologie, de diagnostic et de traitement. Le SHP se manifeste par une oxygénation artérielle anormale, liée à la présence de dilatations vasculaires intrapulmonaires. En revanche, l'HPP est une hypertension artérielle pulmonaire, développée dans le contexte d'une hypertension portale et d'une élévation des résistances vasculaires pulmonaires. Il est important d'identifier et d'évaluer la sévérité de ces deux maladies, en particulier chez les candidats à une transplantation hépatique, en raison de leur association à une morbi-mortalité plus importante.

[Resting heart rate: how to use it for cardiovascular prevention?]. / Fréquence cardiaque de repos: quelle utilité pour la prévention cardiovasculaire?

Resting heart rate is a very accessible clinical parameter in medical practice. Several observational studies have described the link between resting heart rate and the risk of cardiovascular events. An elevated resting heart rate was associated with an increased risk of heart failure and cardiovascular mortality, independently of cardiovascular risk factors. By contrast, interventional studies have shown that reducing heart rate with drugs was beneficial only in patients with pre-existing heart failure or those with coronary heart disease. We aim to review the role and implications of resting heart rate for cardiovascular prevention.

[Transthyretin-related hereditary amyloidosis]. / Amyloïdose héréditaire à transthyrétine.

Transthyretin-related hereditary amyloidosis (ATTR) is a progressive and potentially lethal genetic disorder, transmitted as an autosomal dominant trait. Tissue injury is induced by amyloid fibrils consisting of mutated transthyretin. The symptomatology and clinical course of ATTR is highly variable but typically causes peripheral polyneuropathy and autonomic dysfunction, leading to death within 10 years. As transthyretin is produced mainly in the liver, liver transplantation was the first successful therapeutic approach. Several disease-modifying treatments, including transthyretin stabilizers and gene therapy, are now available or in clinical development, with promising results.

L'amyloïdose héréditaire à transthyrétine (ATTR) est une maladie génétique progressive et potentiellement fatale, transmise sur un mode autosomique dominant. Les lésions organiques sont induites par des dépôts tissulaires de fibrilles amyloïdes, consécutifs à une mutation de la transthyrétine. L'ATTR cause typiquement une polyneuropathie ainsi qu'une dysautonomie, amenant au décès, en moyenne dix ans après le diagnostic. La transthyrétine étant produite surtout par le foie, la transplantation hépatique permet d'arrêter la progression de la maladie dans 70 % des cas, à long terme. De nouvelles thérapies modifiant le cours de la maladie, telles que les stabilisateurs de la transthyrétine et la thérapie génique, sont disponibles ou en développement clinique, avec des résultats prometteurs.

[Cardiology update in 2015]. / Cardiologie.

The present review provides a selected choice of clinical trials and therapeutic advances in the field of cardiology in 2015. A new treatment option in heart failure will become available this year in Switzerland. In interventional cardiology, new trials have been published on the duration of dual antiplatelet therapy, the new stents with bioresorbable scaffold and the long-term results of TAVR in patients who are not surgical candidates or at high surgical risk. RegardingAF the BRIDGE trial provides new evidences to guide the management of patients during warfarin interruption for surgery. Recent publications are changing the paradigm of AF treatment by showing a major impact of the management of cardiometabolic risk factors. Finally, refined criteria for ECG interpretation in athletes have been recently proposed to reduce the burden of false-positive screening.

[Cardiology update in 2014]. / Cardiologie.

Important clinical trials and therapeutic advances in the field of cardiology have been presented in 2014. New evidences on the management of acute myocardial infarction and the duration of dual antiplatelet therapy after coronary stent implantation have been published. A new class of therapeutic agents seems to offer promising perspectives for patients with heart failure and reduced ejection fraction. The new generation of subcutaneous or MRI-compatible implantable defibrillators is a major technological breakthrough. Finally, the European Society of Cardiology published new recommendations for the management of patients with cardiovascular diseases. This selective review of the literature summarizes the most important studies in the field of interventional cardiology, rhythmology, heart failure and cardiac imaging.

Clinical outcomes of HeartMate 3 left ventricular assist device support with a Bridge to Transplant vs a Destination Therapy strategy: a single-centre retrospective cohort.

INTRODUCTION: Real-world outcomes with the HeartMate 3 left ventricular assist device (LVAD) depending on whether it's a bridge to transplantation (BTT) or destination therapy (DT) are poorly studied. We aimed to compare the profile and clinical outcomes of patients supported with HeartMate 3 according to a BTT or a DT pre-implantation strategy. METHODS: All patients consecutively implanted with HeartMate 3 at our centre (University Hospital of Lausanne, Switzerland) in 2015-2022 were analysed in a retrospective observational study. Indications for HeartMate 3 implantation were advanced heart failure despite optimal medical treatment. Patients were treated with a vitamin K antagonist anticoagulant combined with antiplatelet therapy after HeartMate 3 implantation and were followed up monthly at our institution. RESULTS: Among 71 patients implanted with HeartMate 3 between 2015 and 2022, 51 (71.8%) were implanted as a BTT and 20 (28.2%) as DT. Their median age was 58 (IQR: 52-69) years and 84% of patients were classified as INTERMACS profiles 2-4. The median follow-up duration was 18.3 (IQR: 7.5-33.9) months. Patients in the DT group were older than those in the BTT group (p <0.001) and had more chronic renal failure (p <0.001). They also had a lower 5-year survival rate (mean ± standard error: 87.3 ± 5.6% vs 49.4 ± 15.1%) and more adverse events such as renal dysfunction requiring temporary perioperative dialysis (p = 0.08) or bleeding (p = 0.06). CONCLUSION: Although patients supported with HeartMate 3 have favourable survival, those with LVAD-DT have poorer outcomes. There is a need to better select patients eligible for LVAD-DT in order to limit the burden of adverse events and improve their prognosis.

Comparison of HTK-Custodiol and St-Thomas solution as cardiac preservation solutions on early and midterm outcomes following heart transplantation.

OBJECTIVES: The choice of the cardiac preservation solution for myocardial protection at time of heart procurement remains controversial and uncertainties persist regarding its effect on the early and midterm heart transplantation (HTx) outcomes. We retrospectively compared our adult HTx performed with 2 different solutions, in terms of hospital mortality, mid-term survival, inotropic score, primary graft dysfunction and rejection score. METHODS: From January 2009 to December 2020, 154 consecutive HTx of adult patients, followed up in pre- and post-transplantation by 2 different tertiary centres, were performed at the University Hospital of Lausanne, Switzerland. From 2009 to 2015, the cardiac preservation solution used was exclusively St-Thomas, whereafter an institutional decision was made to use HTK-Custodiol only. Patients were classified in 2 groups accordingly. RESULTS: There were 75 patients in the St-Thomas group and 79 patients in the HTK-Custodiol group. The 2 groups were comparable in terms of preoperative and intraoperative characteristics. Postoperatively, compared to the St-Thomas group, the Custodiol group patients showed significantly lower inotropic scores [median (interquartile range): 35.7 (17.5-60.2) vs 71.8 (31.8-127), P < 0.001], rejection scores [0.08 (0.0-0.25) vs 0.14 (0.05-0.5), P = 0.036] and 30-day mortality rate (2.5% vs 14.7%, P = 0.007) even after adjusting for potential confounders. Microscopic analysis of the endomyocardial biopsies also showed less specific histological features of subendothelial ischaemia (3.8% vs 17.3%, P = 0.006). There was no difference in primary graft dysfunction requiring postoperative extracorporeal membrane oxygenation. The use of HTK-Custodiol solution significantly improved midterm survival (Custodiol versus St-Thomas: hazard ratio = 0.20, 95% confidence interval: 0.069-0.60, P = 0.004). CONCLUSIONS: This retrospective study comparing St-Thomas solution and HTK-Custodiol as myocardial protection during heart procurement showed that Custodiol improves outcomes after HTx, including postoperative inotropic score, rejection score, 30-day mortality and midterm survival.

The transpulmonary pressure gradient for the diagnosis of pulmonary vascular disease.

The transpulmonary pressure gradient (TPG), defined by the difference between mean pulmonary arterial pressure (P(pa)) and left atrial pressure (P(la); commonly estimated by pulmonary capillary wedge pressure: P(pcw)) has been recommended for the detection of intrinsic pulmonary vascular disease in left-heart conditions associated with increased pulmonary venous pressure. In these patients, a TPG of >12 mmHg would result in a diagnosis of "out of proportion" pulmonary hypertension. This value is arbitrary, because the gradient is sensitive to changes in cardiac output and both recruitment and distension of the pulmonary vessels, which decrease the upstream transmission of P(la). Furthermore, pulmonary blood flow is pulsatile, with systolic P(pa) and mean P(pa) determined by stroke volume and arterial compliance. It may, therefore, be preferable to rely on a gradient between diastolic P(pa) and P(pcw). The measurement of a diastolic P(pa)/P(pcw) gradient (DPG) combined with systemic blood pressure and cardiac output allows for a step-by-step differential diagnosis between pulmonary vascular disease, high output or high left-heart filling pressure state, and sepsis. The DPG is superior to the TPG for the diagnosis of "out of proportion" pulmonary hypertension.