Nicolas Lamblin

Background: Mavacamten has been shown to be efficient in the treatment of obstructive hypertrophic cardiomyopathy (HOCM). However, its use may be associated with toxicity and subsequent adverse events. CYP2C19 genotyping is therefore recommended to optimize dosing and minimize risks in daily practice. Case summary: We report the case of a 39-year-old woman with a history of sleeve gastrectomy and HOCM. She was initiated on mavacamten 5 mg once daily (CYP2C19 genotyping showed no mutation) because of persistent significant obstruction and dyspnoea (NYHA class II) under nebivolol. Although initial tolerance was good with a reassuring transthoracic echocardiography at 4 months, she experienced a severe cardiogenic shock related to mavacamten overdose in the context of esomeprazole initiation (proton pump inhibitor that strongly interacts with the cytochrome CYP2C19 and CYP3A4) for an oesophageal pyrosis by her general practitioner 8 months later. Notably, the toxicity could be completely overcome by rifampicin initiation (600 mg twice daily for 3 days), which allowed the normalization of the plasma level of mavacamten within a few days and patient recovery. Discussion: The present case highlights that drug interactions in patients with HOCM receiving mavacamten are critical and may lead to a high level of toxicity and severe heart failure events, including cardiogenic shocks. Patient and caregiver information about these potential interactions is highly important. This case also emphasizes that the dosage of mavacamten is now available (and should be used in specific situations) and that mavacamten toxicity can rapidly be overcome by early rifampicin administration, a strong hepatic enzyme inducer.

Aims: Post-capillary pulmonary hypertension (pcPH) is a frequent complication of heart failure (HF), associated with poor outcomes. While right heart catheterization (RHC) is the diagnostic gold standard, echocardiographic indices such as left atrial volume index (LAVI) and the TAPSE/PASP ratio may offer non-invasive prognostic value. Objectives: To assess the prognostic utility of LAVI and TAPSE/PASP compared with invasive haemodynamic parameters in patients with HF and pcPH undergoing RHC. Methods and results: The PH–HF study is a prospective multicentre cohort of adults with chronic HF and confirmed pcPH (mPAP > 20 mmHg and pulmonary arterial wedge pressure > 15 mmHg) enrolled across 13 French centres (2012–2018). Patients with precapillary PH or severe pulmonary/renal comorbidities were excluded. The primary outcome was a 3-year composite of all-cause mortality, urgent heart transplantation or LVAD, or unplanned HF hospitalization. Cox regression was used for survival analyses. Overall, 55% of patients met the composite echocardiographic risk criterion (LAVI > 35 mL/m² or TAPSE/PASP < 0.40), which was associated with increased risk of adverse events (HR 1.97, 95% CI 1.41–2.75; P < 0.0001). Results were consistent across HFrEF and HFpEF phenotypes. In a multivariable model including the MAGGIC score, both the echocardiographic criterion and the clinical score remained independently associated with outcomes, supporting their complementary value in risk stratification. Conclusion: LAVI and TAPSE/PASP are strong, non-invasive predictors of adverse outcomes in HF with pcPH and may enhance prognostic assessment beyond invasive haemodynamics and clinical scores.

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. 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). 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). 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 PH-HF multicentre study. The PH-HF prospective multicentre study validates the new PH definition from the ESC/ERS guidelines among 662 patients with HF and RHC at rest. CpcPH, combined post-capillary PH; IpcPH, isolated post-capillary PH; mPAP, mean pulmonary artery pressure; PH, pulmonary hypertension; PVR, pulmonary vascular resistance; RHC, right heart catheterization.

Aims: The clinical significance and feasibility of the recently described non-invasive parameters exploring ventricular–arterial coupling (VAC) remain uncertain. This study aimed to assess VAC parameters for prognostic stratification in stable patients with left ventricular ejection fraction (LVEF) ≥40% following myocardial infarction (MI).Methods and results: Between 2018 and 2021, patients with LVEF ≥40% were evaluated 1 month following MI using transthoracic echocardiography (TTE) and arterial tonometry at rest and after a handgrip test. VAC was studied via the ratio between arterial elastance (Ea) and end-systolic LV elastance (Ees) and between pulse wave velocity (PWV) and global longitudinal strain (GLS). Patients were followed for major adverse cardiovascular events (MACE): all-cause death, acute heart failure, stroke, AMI, and urgent cardiovascular hospitalization. Among the 374 patients included, Ea/Ees and PWV/GLS were obtained at rest for 354 (95%) and 253 patients (68%), respectively. Isometric exercise was workable in 335 patients (85%). During a median follow-up of 32 months (interquartile range: 16–42), 41 (11%) MACE occurred. Patients presenting MACE were significantly older and had a higher prevalence of peripheral arterial disease, lower GLS, higher Ea, PWV, and PWV/GLS ratio. The Ea/Ees ratio and standard TTE parameters during isometric exercise were not associated with MACE. After adjustment, the PWV/GLS ratio was the only VAC parameter independently associated with outcome. Receiver operating characteristic curve analysis identified a PWV/GLS ratio >0.70 (Youden’s index = 0.37) as the best threshold to identify patients developing MACE: hazard ratio (95% confidence interval) = 2.2 (1.14–4.27), P = 0.02.Conclusion: The PWV/GLS ratio, assessed 1 month after MI, identifies a group of patients at higher risk of MACE providing additional value on top of conventional non-invasive parameters.

There is a large heterogeneity among patients presenting with cardiogenic shock (CS). It is crucial to better apprehend this heterogeneity in order to adapt treatments and improve prognoses in these severe patients. Notably, the presence (or absence) of a pre-existing history of chronic heart failure (CHF) at time of CS onset may be a significant part of this heterogeneity, and data focusing on this aspect are lacking. We aimed to compare CS patients with new-onset HF to those with worsening CHF in the multicenter FRENSHOCK registry. Altogether, 772 CS patients were prospectively included: 433 with a previous history of CHF and 339 without. Worsening CHF patients were older (68 +/− 13.4 vs. 62.7 +/− 16.2, p < 0.001) and had a greater burden of extra-cardiac comorbidities. At admission, acute myocardial infarction was predominantly observed in the new-onset HF group (49.9% vs. 25.6%, p < 0.001). When focusing on hemodynamic parameters, worsening CHF patients showed more congestion and higher ventricular filling pressures. Worsening CHF patients experienced higher in-hospital all-cause mortality (31.3% vs. 24.2%, p = 0.029). Our results emphasize the great heterogeneity of the patients presenting with CS. Worsening CHF patients had higher risk profiles, and this translated to a 30% increase in in-hospital all-cause mortality. The heterogeneity of this population prompts us to better determine the phenotype of CS patients to adapt their management.

Background: Current data regarding the impact of diabetes mellitus (DM) on cardiovascular mortality in patients with aortic stenosis (AS) are restricted to severe AS or aortic valve replacement (AVR) trials. Purpose: To investigate cardiovascular mortality according to DM across the entire spectrum of AS outpatients. Methods: Between May 2016 and December 2017, patients with mild (peak aortic velocity=2.5–2.9m/s), moderate (3–3.9m/s) and severe (≥4m/s) AS graded by echocardiography were included during outpatient cardiology visits in the Nord-Pas-de-Calais region in France and followed-up for modes of death. Results: Among 2,703 patients, 820 (30.3%) had DM, mean age was 76±10.8 years with 46.6% of women and a relatively high prevalence of underlying cardiovascular diseases. There were 200 cardiovascular deaths prior to AVR during the 2.1 years (IQR 1.4–2.7) follow-up period. In adjusted analyses, DM was significantly associated with cardiovascular mortality (HR=1.40, 95% CI 1.04–1.89; P=0.029). In mild or moderate AS, the cardiovascular mortality of diabetic patients was similar to that of nondiabetic patients (Figuer 1). In severe AS, DM was associated with higher cardiovascular mortality (HR=2.65, 95% CI 1.50–4.68; P=0.001). This was almost exclusively related to a higher risk of death from heart failure (HR=2.61, 95% CI 1.15–5.92; P=0.022) and sudden death (HR=3.33, 95% CI 1.28–8.67; P=0.014) (Figure 2). Conclusion: The effect of DM on cardiovascular mortality varied across AS severity. Despite no association between DM and outcomes in mild/moderate AS patients, DM was strongly associated with death from heart failure and sudden death in severe AS patients. Funding Acknowledgement: Type of funding sources: Public Institution(s). Main funding source(s): Fédération Française de Cardiologie

To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Between 2018 and 2020, 244 patients admitted in the cardiac intensive care unit in Lille University Hospital for AMI were included. One-month following AMI, comprehensive transthoracic echocardiography (TTE) was performed to assess parameters of myocardial function. Patients were then followed for major events (ME): cardiovascular death, heart failure, and unplanned coronary revascularization. At 1-month, half of the population was symptomatic (NYHA ≥ II), and medical therapy was almost optimized (angiotensin-converting enzyme inhibitor/angiotensin 2 receptor blocker in 95.5%, beta-blockers in 96.3%, DAPT in 94.7%, and statins in 97.1%). After a median follow-up of 681 (interquartile range: 538–840) days, ME occurred in 26 patients (10.7%). Patients presenting ME were older (65.5 ± 14.2 vs. 58.1 ± 12.1years, P = 0.005) with a higher prevalence of hypertension (65.4 vs. 36.2%, P = 0.004), more impaired left ventricular (LV) function as assessed by LV ejection fraction (P = 0.07), global longitudinal strain (P = 0.03), or MW parameters [P = 0.01 for global work efficiency (GWE)], and greater LV and left atrium dilatations (P = 0.06 for left ventricular end-diastolic volume index and P = 0.03 for left atrial volume index). After adjustment, GWE was the only TTE parameter independently associated with long-term occurrence of ME (P = 0.02). A GWE value P = 0.0041). Lower GWE at 1 month after AMI is independently associated with higher ME rates. A GWE <91% can improve the post-AMI patient risk stratification. Flow chart summarizing the prognostic value of global work efficiency (GWE) 1-month after myocardial infarction (MI). GWE <91% was independently associated with adverse events.

Bronchopulmonary infections are a major trigger of cardiac decompensation and are frequently associated with hospitalizations in patients with heart failure (HF). Adverse cardiac effects associated with respiratory infections, more specifically Streptococcus pneumoniae and influenza infections, are the consequence of inflammatory processes and thrombotic events. For both influenza and pneumococcal vaccinations, large multicenter randomized clinical trials are needed to evaluate their efficacy in preventing cardiovascular events, especially in HF patients. No study to date has evaluated the protective effect of the COVID-19 vaccine in patients with HF. Different guidelines recommend annual influenza vaccination for patients with established cardiovascular disease and also recommend pneumococcal vaccination in patients with HF. The Heart Failure group of the French Society of Cardiology recently strongly recommended vaccination against COVID-19 in HF patients. Nevertheless, the implementation of vaccination recommendations against respiratory infections in HF patients remains suboptimal. This suggests that a national health policy is needed to improve vaccination coverage, involving not only the general practitioner, but also other health providers, such as cardiologists, nurses, and pharmacists. This review first summarizes the pathophysiology of the interrelationships between inflammation, infection, and HF. Then, we describe the current clinical knowledge concerning the protective effect of vaccines against respiratory diseases (influenza, pneumococcal infection, and COVID-19) in patients with HF and finally we propose how vaccination coverage could be improved in these patients.

Multidisciplinary management of worsening heart failure (HF) in the elderly improves survival. To ensure patients have access to adequate care, the current HF and French health authority guidelines advise establishing a clearly defined HF patient pathway. This pathway involves coordinating multiple disciplines to manage decompensating HF. Yet, recent registry data indicate that insufficient numbers of patients receive specialised cardiology care, which increases the risk of rehospitalisation and mortality. The patient pathway in France involves three key stages: presentation with decompensated HF, stabilisation within a hospital setting and transitional care back out into the community. In each of these three phases, HF diagnosis, severity and precipitating factors need to be promptly identified and managed. This is particularly pertinent in older, frail patients who may present with atypical symptoms or coexisting comorbidities and for whom geriatric evaluation may be needed or specific geriatric syndrome management implemented. In the transition phase, multi-professional post-discharge management must be coordinated with community health care professionals. When the patient is discharged, HF medication must be optimised, and patients educated about self-care and monitoring symptoms. This review provides practical guidance to clinicians managing worsening HF in the elderly.