Feasibility and prognostic significance of ventricular-arterial coupling after myocardial infarction: the RIGID-MI cohort.

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.

Clinical significance of myocardial work parameters after acute myocardial infarction.

Aims: To investigate the additional prognostic value of myocardial work (MW) parameters following acute myocardial infarction (AMI). Methods and results: 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 <91% was selected to identify patients at higher ME risk (hazard ratio: 95% confidence interval) = 2.94 (1.36-6.35), P = 0.0041). Conclusion: 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.

Clinical significance of electrocardiographic markers of myocardial damage prior to aortic valve replacement.

BACKGROUND: Pre-operative myocardial fibrosis and remodeling impact on outcomes after aortic valve replacement (AVR). We aimed at investigating the prognostic impact of preoperative electrocardiographic (ECG) markers of left ventricular (LV) myocardial damage, i.e. bundle branch block (BBB) and ECG strain pattern after (surgical or transcatheter) AVR for severe aortic stenosis (AS). METHODS: Between April 2008 and October 2017, we explored consecutive patients referred to our Heart Valve Clinic for first AVR for severe AS. Detailed pre-operative phenotyping and ECG analysis were performed. Patients were followed-up after AVR for major cardiac events (ME), i.e. cardiovascular death, cardiac hospitalization for acute heart failure and stroke. RESULTS: BBB and ECG strain were respectively observed in 13.5 and 21% of the 1122 patients included. These ECG markers identified a subgroup of older patients, with higher NYHA class and more advanced myocardial disease as detected by echocardiography, i.e. higher LV mass and lower LV ejection fraction, global longitudinal strain and integrated backscatter, than patients without ECG strain or BBB. ME occurred in 212 (18.6%) patients during a mean follow-up of 4.4 ± 1.5 years with higher incidence in case of ECG strain or BBB (HR 1.56, 95%CI 1.13-2.14, p = 0.006; HR 1.47, 95%CI 1.02-2.13, p = 0.04 respectively). The prognostic value of ECG strain remained significant after adjustment for age, diabetes and pre-operative LVEF. CONCLUSIONS: Pre-operative ECG markers of myocardial damage identify a subgroup of AS patients at high risk of post-AVR cardiovascular complications irrespective of other prognostic factors and should help the multiparametric staging of cardiac damage to guide AVR.

Epicardial fat amount is associated with the magnitude of left ventricular remodeling in aortic stenosis.

Both genetic and environmental factors interact to control left ventricular (LV) remodeling in the context of aortic stenosis (AS). Epicardial adipose tissue (EAT) is a specific visceral adipose tissue with paracrine properties in close contact with the myocardium. We sought to assess determinants of EAT amount and its association with the magnitude and pattern of LV remodeling in patients suffering from severe AS. Between January 2014 and September 2017, we prospectively explored consecutive patients referred to our Heart Valve Center for SAVR presenting with severe AS and normal left ventricular ejection fraction (> 50%). Comprehensive transthoracic echocardiography (TTE) including assessment of LV remodeling and EAT amount were performed. 202 patients were included. EAT was significantly larger in elderly, diabetic and obese patients. EAT thickness was correlated positively with indexed LV mass in AS (r2 = 0.21; p < 0.0001) as well as severe LV remodeling pattern. Importantly, this observation persisted after adjustment for other factors associated with LV remodeling (ß ± SE = 1.74 ± 0.34; p < 0.0001). Large amounts of EAT are positively and independently associated with more pronounced and severe LV remodeling in severe AS. Further exploration regarding the impact of functional properties of EAT on LV remodeling is required.

Peri-operative acute kidney injury upon cardiac surgery time-of-day.

BACKGROUND: A relevant morning-afternoon variation in ischemia-reperfusion (IR) insult after cardiac surgery has been demonstrated. We speculated that the biorhythm might also impact systemic reactions involved in acute kidney injury (AKI) following cardiac surgery. We aimed at investigating incidence, determinants and prognostic impact of AKI in a large cohort of patients referred for surgical aortic valve replacement (SAVR) according to surgery time-of-day. METHODS: Between 2009 and 2015, we explored consecutive patients referred to our Heart Valve Center (CHU Lille) for first SAVR. Patients undergoing morning and afternoon SAVR were matched into pairs by propensity score and followed for major events (ME) i.e. cardiovascular death, cardiac hospitalization for acute heart failure (HF) and post-operative myocardial infarction. AKI was defined using KDIGO classification. RESULTS: In the matched population (n = 596 patients), AKI occurred in 20% of patients. After multivariable adjustment, medical history of hypertension, pre-operative renal function impairment and cardio-pulmonary bypass duration were independent predictors of AKI onset. Post-operative AKI was significantly associated with increased occurrence of ME and specifically of cardiac hospitalization for HF (p = 0.0035 and p = 0.0071, respectively) during the 500 days following SAVR. Finally, AKI occurrence and severity were similar between morning and afternoon groups (p = 0.98 and p = 0.99, respectively). CONCLUSION: We showed that despite current high-quality patient management during and following SAVR, peri-operative AKI remains frequent, developing in 20% of patients, and clearly worsens mid-term post-operative outcomes. AKI more often develops in patients with pre-operative chronic kidney disease and long duration of cardiac surgery but is not influenced by surgery time-of-day.

Daytime variation of perioperative myocardial injury in cardiac surgery and its prevention by Rev-Erbα antagonism: a single-centre propensity-matched cohort study and a randomised study.

BACKGROUND: On-pump cardiac surgery provokes a predictable perioperative myocardial ischaemia-reperfusion injury which is associated with poor clinical outcomes. We determined the occurrence of time-of-the-day variation in perioperative myocardial injury in patients undergoing aortic valve replacement and its molecular mechanisms. METHODS: We studied the incidence of major adverse cardiac events in a prospective observational single-centre cohort study of patients with severe aortic stenosis and preserved left ventricular ejection fraction (>50%) who were referred to our cardiovascular surgery department at Lille University Hospital (Lille, France) for aortic valve replacement and underwent surgery in the morning or afternoon. Patients were matched into pairs by propensity score. We also did a randomised study, in which we evaluated perioperative myocardial injury and myocardial samples of patients randomly assigned (1:1) via permuted block randomisation (block size of eight) to undergo isolated aortic valve replacement surgery either in the morning or afternoon. We also evaluated human and rodent myocardium in ex-vivo hypoxia-reoxygenation models and did a transcriptomic analysis in myocardial samples from the randomised patients to identify the signalling pathway(s) involved. The primary objective of the study was to assess whether myocardial tolerance of ischaemia-reperfusion differed depending on the timing of aortic valve replacement surgery (morning vs afternoon), as measured by the occurrence of major adverse cardiovascular events (cardiovascular death, myocardial infarction, and admission to hospital for acute heart failure). The randomised study is registered with ClinicalTrials.gov, number NCT02812901. FINDINGS: In the cohort study (n=596 patients in matched pairs who underwent either morning surgery [n=298] or afternoon surgery [n=298]), during the 500 days following aortic valve replacement, the incidence of major adverse cardiac events was lower in the afternoon surgery group than in the morning group: hazard ratio 0·50 (95% CI 0·32-0·77; p=0·0021). In the randomised study, 88 patients were randomly assigned to undergo surgery in the morning (n=44) or afternoon (n=44); perioperative myocardial injury assessed with the geometric mean of perioperative cardiac troponin T release was significantly lower in the afternoon group than in the morning group (estimated ratio of geometric means for afternoon to morning of 0·79 [95% CI 0·68-0·93; p=0·0045]). Ex-vivo analysis of human myocardium revealed an intrinsic morning-afternoon variation in hypoxia-reoxygenation tolerance, concomitant with transcriptional alterations in circadian gene expression with the nuclear receptor Rev-Erbα being highest in the morning. In a mouse Langendorff model of hypoxia-reoxygenation myocardial injury, Rev-Erbα gene deletion or antagonist treatment reduced injury at the time of sleep-to-wake transition, through an increase in the expression of the ischaemia-reperfusion injury modulator CDKN1a/p21. INTERPRETATION: Perioperative myocardial injury is transcriptionally orchestrated by the circadian clock in patients undergoing aortic valve replacement, and Rev-Erbα antagonism seems to be a pharmacological strategy for cardioprotection. Afternoon surgery might provide perioperative myocardial protection and lead to improved patient outcomes compared with morning surgery. FUNDING: Fondation de France, Fédération Française de Cardiologie, EU-FP7-Eurhythdia, Agence Nationale pour la Recherche ANR-10-LABX-46, and CPER-Centre Transdisciplinaire de Recherche sur la Longévité.