Abstract
Despite advances in cardioprotection, new therapeutic strategies capable of preventing ischemia-reperfusion injury of patients are still needed. Here, we discover that ...sarcoplasmic/endoplasmic reticulum Ca
2+
ATPase (SERCA2) phosphorylation at serine 663 is a clinical and pathophysiological event of cardiac function. Indeed, the phosphorylation level of SERCA2 at serine 663 is increased in ischemic hearts of patients and mouse. Analyses on different human cell lines indicate that preventing serine 663 phosphorylation significantly increases SERCA2 activity and protects against cell death, by counteracting cytosolic and mitochondrial Ca
2+
overload. By identifying the phosphorylation level of SERCA2 at serine 663 as an essential regulator of SERCA2 activity, Ca
2+
homeostasis and infarct size, these data contribute to a more comprehensive understanding of the excitation/contraction coupling of cardiomyocytes and establish the pathophysiological role and the therapeutic potential of SERCA2 modulation in acute myocardial infarction, based on the hotspot phosphorylation level of SERCA2 at serine 663 residue.
: Vasoplegic syndrome after orthotopic heart transplantation (OHT) or left ventricular assist device (LVAD) implantation is a rare but highly lethal syndrome with complex etiologies. The objective of ...this study was to assess if the preoperative use of sacubitril-valsartan combination is associated with an increased vasoplegic syndrome (VS) frequency after OHT or LVAD implantation and its relationship with 30-day mortality.
A retrospective review of perioperative data, between January 2016 and December 2017, from 73 consecutive OHT and LVAD surgery adult patients at our institution was performed. VS was defined as normal cardiac output with persistent low systemic resistance requiring a norepinephrine intravenous perfusion > 0.5 µg/kg/min and the absence of sepsis or hemorrhagic shock within 48 h after surgery. Patients were all followed-up for adverse events and all-cause mortality at 30 days.
In our cohort of 73 patients (median age 51.7 years, 65% male patients), 25 (34%) patients developed VS. Twenty-two (30.1%) patients were on ARNI at the time of surgery, 31 (42.5%) were on other RAS blockers, 12 (16.4%) were on norepinephrine and 8 (11%) had no pre-operative drug. The pre-operative use of any vasoactive agent, was not significantly associated with VS (OR = 1.36; IC95% 0.78; 2.35;
0.38). The pre-operative use of an ARNI compared to all other groups was not significantly associated with VS (OR = 2.0; IC95% 0.71; 5.62;
= 0.19). The pre-operative use of an ARNI compared to other RAS blockers was also not significantly associated with VS (OR = 1.25; IC95% 0.37; 4.26;
= 0.72). At 30 days, 18 (24.7%) patients had died. The pre-operative treatment with ARNI, or other RAS inhibitors was associated with a significantly lower rate of death compared to the absence of treatment (HR = 0.11; IC95% 0.02; 0.55;
= 0.009 for ARNI and HR = 0.20; IC95% 0.06; 0.69;
= 0.011 for other RASi).
Preoperative use of sacubitril-valsartan was not significantly associated with development of vasoplegic syndrome in patients undergoing OHT or LVAD surgery. Furthermore, our data suggests a significant 30-day survival benefit with efficient renin-angiotensin blockade before surgery.
Introduction: De novo anti-HLA donor specific antibodies (DSA) have been inconsistently associated with cardiac allograft vasculopathy (CAV) and long-term mortality. We tested whether C3d-binding de ...novo DSA were associated with CAV or long-term-survival. Methods: We included 282 consecutive patients without preformed DSA on coronary angiography between 2010 and 2012. Angiographies were classified according to CAV ISHLT grading. The primary outcome was a composite criterion of severe CAV or mortality. As the impact of de novo antibodies should be assessed only after appearance, we used a Cox regression with time-dependent covariables. Results: Of the 282 patients, 51(18%) developed de novo DSA during follow-up, 29 patients had DSA with C3d-binding ability (DSA+C3d+), and 22 were without C3d-binding ability (DSA+C3d-). Compared with patients without DSA, DSA+C3d+ patients had an increased risk for the primary outcome of severe CAV or mortality (adjusted HR = 4.31 (2.40−7.74) p < 0.001) and long-term mortality (adjusted HR = 3.48 (1.97−6.15) p < 0.001) whereas DSA+C3d- did not (adjusted HR = 1.04 (0.43−2.47) p = 0.937 for primary outcome and HR = 1.08 (0.45−2.61) p = 0.866 for mortality). Conclusion: According to this large monocentric study in heart transplant patients, donor specific antibodies were associated with worse clinical outcome when binding complement. DSA and their complement-binding ability should thus be screened for to optimize heart transplant patient follow-up.
Introduction: Heart transplantation (HT) remains the gold-standard treatment but is conditioned by organ shortage. This study aimed to evaluate the value of Forrester classification and determine ...which congestion criteria had the best prognostic value to predict cardiorenal events on heart transplant waiting list. Methods and results: One hundred consecutive patients (54 years old, 72% men) with available right heart catheterization (RHC) listed in our center for HT between 2014 and 2019 were included. Cardiac catheterization measurements were obtained at the time of HT listing evaluation. Patients were classified according to perfusion and congestion status in four groups: “warm and dry”, “warm and wet”, “cold and dry”, and “cold and wet”. pWet was used to classify patients with pulmonary congestion and sWet for systemic congestion. The primary endpoint was the rate of a composite criteria of cardiogenic shock, acute kidney injury, and acute heart failure. Secondary endpoint was the incidence of waitlist death, emergency HT, or left ventricular assist device (LVAD) implantation at 12 months evaluated by Kaplan–Meier curves and log-rank test. Only Forrester classification according to systemic congestion was associated with the primary composite endpoint (p = 0.011), while patients’ profile according to pulmonary congestion was not (p = 0.331). Similarly, only the Forrester classification according to systemic congestion predicted waitlist death, emergency HT, or LVAD implantation at 12 months, with p = 0.010 and p = 0.189 for systemic and pulmonary congestion, respectively. Moreover, systemic congestion was the main driver of cardiorenal events on waitlist. Conclusions: Forrester classification according to systemic congestion is associated with cardiorenal outcomes in patients listed for heart transplant and the risk of waitlist death, emergency HT, or LVAD implantation at 12 months.
The prognostic value of 'high dose' loop diuretics in advanced heart failure outpatients is unclear. We aimed to assess the prognosis associated with loop diuretic dose in ambulatory patients ...awaiting heart transplantation (HT).
All ambulatory patients (n = 700, median age 55 years and 70% men) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 were included. Patients were divided into 'low dose', 'intermediate dose', and 'high dose' loop diuretics corresponding to furosemide equivalent doses of ≤40, 40-250, and >250 mg, respectively. The primary outcome was a combined criterion of waitlist death and urgent HT. N-terminal pro-B-type natriuretic peptide, creatinine levels, pulmonary capillary wedge pressure, and pulmonary pressures gradually increased with higher diuretic dose. At 12 months, the risk of waitlist death/urgent HT was 7.4%, 19.2%, and 25.6% (P = 0.001) for 'low dose', 'intermediate dose', and 'high dose' patients, respectively. When adjusting for confounders, including natriuretic peptides, hepatic, and renal function, the 'high dose' group was associated with increased waitlist mortality or urgent HT adjusted hazard ratio (HR) 2.23, 1.33 to 3.73; P = 0.002 and a six-fold higher risk of waitlist death (adjusted HR 6.18, 2.16 to 17.72; P < 0.001) when compared with the 'low dose' group. 'Intermediate doses' were not significantly associated with these two outcomes in adjusted models (P > 0.05).
A 'high dose' of loop diuretics is strongly associated with residual congestion and is a predictor of outcome in patients awaiting HT despite adjustment for classical cardiorenal risk factors. This routine variable may be helpful for risk stratification of pre-HT patients.
Aims
The value of Forrester's perfusion/congestion profiles assessed by invasive catheter evaluation in non‐inotrope advanced heart failure patients listed for heart transplant (HT) is unclear. We ...aimed to assess the value of haemodynamic evaluation according to Forrester's profiles to predict events on the HT waitlist.
Methods and results
All non‐inotrope patients (n = 837, 79% ambulatory at listing) registered on the French national HT waiting list between 1 January 2013 and 31 December 2019 with right heart catheterization (RHC) were included. The primary outcome was a combined criteria of waitlist death, delisting for aggravation, urgent HT or left ventricular assist device implantation. Secondary outcome was waitlist death. The ‘warm‐dry’, ‘cold‐dry’, ‘warm‐wet’, and ‘cold‐wet’ profiles represented 27%, 18%, 27%, and 28% of patients, respectively. At 12 months, the respective rates of primary outcome were 15%, 17%, 25%, and 29% (P = 0.008). Taking the ‘warm‐dry’ category as reference, a significant increase in the risk of primary outcome was observed only in the ‘wet’ categories, irrespectively of ‘warm/cold’ status: hazard ratios, 1.50; 1.06–2.13; P = 0.024 in ‘warm‐wet’ and 1.77; 1. 25–2.49; P = 0.001 in ‘cold‐wet’.
Conclusions
Haemodynamic assessment of advanced HF patients using perfusion/congestion profiles predicts the risk of the combine endpoint of waitlist death, delisting for aggravation, urgent heart transplantation, or left ventricular assist device implantation. ‘Wet’ patients had the worst prognosis, independently of perfusion status, thus placing special emphasis on the cardinal prominence of persistent congestion in advanced HF.
Aims
Health literacy (HL) is a health determinant in cardiovascular diseases as the active participation of patients is essential for optimizing self‐management of these conditions. We aimed to ...estimate the prevalence of low HL level in patients hospitalized for acute myocardial infarction (AMI) or acute decompensated heart failure (ADHF) and explore low HL determinants.
Methods and results
A prospective cross‐sectional study was performed in three cardiology units. HL level was assessed using Brief Health Literacy Screen (BHLS) and categorized as low or adequate. Dimensions of HL were assessed with the Health Literacy Questionnaire (HLQ). Associations with sociodemographic factors, disease history, and comorbidities were explored. A total of 208 patients were included, mean ± SD age was 68.5 ± 14.9 years, and 65.9% were men. Patients with ADHF were significantly older and more often women than AMI patients. Prevalence of low HL was 36% overall, 51% in ADHF patients, and 21% in AMI patients (P < 0.001). After adjustment for sociodemographic factors, patients with lower income (€<10 000 per year, adjusted odds ratio = 10.46 95% confidence interval 2.38; 54.51, P = 0.003) and native language other than French (adjusted odds ratio = 14.36 95% confidence interval 3.76; 66.9, P < 0.002) were more likely to have low HL. ADHF patients presented significantly lower HLQ scores than AMI patients in five out of the nine HLQ dimensions reflecting challenges in access to healthcare.
Conclusions
Prevalence of low HL was higher among ADHF patients than among AMI patients. Low HL ADHF patients needed more support when accessing healthcare services, and these would require more adaptation to respond to low HL patients' needs.
Aims
The heart failure (HF) prognosis in older patients remains poor with a high 5‐years mortality rate more frequently attributed to noncardiovascular causes. The complex interplay between frailty ...and heart failure contribute to poor health outcomes of older adults with HF independently of ejection fraction. The aim of this position paper is to propose a practical management of frailty in older patients with heart failure.
Methods
A panel of multidisciplinary experts on behalf the Heart Failure Working Group of the French Society of Cardiology and on behalf French Society of Geriatrics and Gerontology conducted a systematic literature search on the interlink between frailty and HF, met to propose an early frailty screening by non‐geriatricians and to propose ways to implement management plan of frailty. Statements were agreed by expert consensus.
Results
Clinically relevant aspects of interlink between frailty and HF have been reported to identify the population eligible for screening and the most suitable screening test(s). The frailty screening program proposed focuses on frailty model defined by an accumulation of deficits including geriatric syndromes, comorbidities, for older patients with HF in different settings of care. The management plan of frailty includes optimization of HF pharmacological treatments and non‐surgical device treatment as well as optimization of a global patient‐centred biopsychosocial blended collaborative care pathway.
Conclusion
The current manuscript provides practical recommendations on how to screen and optimize frailty management in older patients with heart failure.
Aims
Abnormal renal function is a common feature in patients on heart transplant waiting lists. This study aimed to identify the haemodynamic parameters associated with decreased estimated glomerular ...filtration rate (eGFR) in patients listed for heart transplantation (HT) and renal function improvement following HT.
Methods and results
A total of 176 adults (52 years old, 81% men) with available right heart catheterization (RHC) listed in our centre for HT between 2014 and 2019 were studied. Cardiac catheterization measurements were obtained at time of HT listing evaluation. Changes in renal function were assessed between RHC and 6 months after HT. Median eGFR was 63 mL/min/1.73 m2 at time of RHC. Central venous pressure > 10 mmHg was associated with a two‐fold increase in the likelihood of eGFR < 60 mL/min/1.73 m2 at time of RHC (adjusted odd ratio, 2.2; 95% confidence interval, 1.1–4.7; P = 0.04). In the 134 patients (76%) who underwent HT during follow‐up, eGFR decreased by 7.9 ± 29.7 mL/min/1.73 m2 from RHC to 6 months after HT. In these patients, low cardiac index (<2.1 L/min/m2) at initial RHC was associated with a (adjusted) 6 month post‐HT eGFR improvement of 12.2 mL/min/1.73 m2 (P = 0.018). Patients with eGFR < 60 mL/min/1.73 m2 and low cardiac index at time of RHC exhibited the greatest eGFR improvement (delta eGFR = 18.3 mL/min/1.73 m2) while patients with eGFR ≥ 60 mL/min/1.73 m2 and normal cardiac index had a marked decrease in eGFR (delta eGFR = −27.7 mL/min/1.73 m2, P < 0.001).
Conclusions
Central venous pressure is the main haemodynamic parameter associated with eGFR < 60 mL/min/1.73 m2 in patients listed for HT. Low cardiac index prior to HT is associated with post‐transplant renal function recovery.
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