Optimal Heart Failure Medical Therapy and Mortality in Survivors of Cardiogenic Shock: Insights From the FRENSHOCK Registry.

BACKGROUND: The effects of pharmacological therapy on cardiogenic shock (CS) survivors have not been extensively studied. Thus, this study investigated the association between guideline-directed heart failure (HF) medical therapy (GDMT) and one-year survival rate in patients who are post-CS. METHODS AND RESULTS: FRENSHOCK (French Observatory on the Management of Cardiogenic Shock in 2016) registry was a prospective multicenter observational survey, conducted in metropolitan French intensive care units and intensive cardiac care units. Of 772 patients, 535 patients were enrolled in the present analysis following the exclusion of 217 in-hospital deaths and 20 patients with missing medical records. Patients with triple GDMT (beta-blockers, renin-angiotensin system inhibitors, and mineralocorticoid receptor antagonists) at discharge (n=112) were likely to have lower left ventricular ejection fraction on admission and at discharge compared with those without triple GDMT (n=423) (22% versus 28%, P<0.001 and 29% versus 37%, P<0.001, respectively). In the overall cohort, the one-year mortality rate was 23%. Triple GDMT prescription was significantly associated with a lower one-year all-cause mortality compared with non-triple GDMT (adjusted hazard ratio 0.44 [95% CI, 0.19-0.80]; P=0.007). Similarly, 2:1 propensity score matching and inverse probability treatment weighting based on the propensity score demonstrated a lower incidence of one-year mortality in the triple GDMT group. As the number of HF drugs increased, a stepwise decrease in mortality was observed (log rank; P<0.001). CONCLUSIONS: In survivors of CS, the one-year mortality rate was significantly lower in those with triple GDMT. Therefore, this study suggests that intensive HF therapy should be considered in patients following CS.

COVID-19 promotes endothelial dysfunction and thrombogenicity: role of proinflammatory cytokines/SGLT2 prooxidant pathway.

BACKGROUND: COVID-19 is associated with an increased risk of cardiovascular complications. Although cytokines have a predominant role in endothelium damage, the precise molecular mechanisms are far from being elucidated. OBJECTIVES: The present study hypothesized that inflammation in patients with COVID-19 contributes to endothelial dysfunction through redox-sensitive SGLT2 overexpression and investigated the protective effect of SGLT2 inhibition by empagliflozin. METHODS: Human plasma samples were collected from patients with acute, subacute, and long COVID-19 (n = 100), patients with non-COVID-19 and cardiovascular risk factors (n = 50), and healthy volunteers (n = 25). Porcine coronary artery endothelial cells (ECs) were incubated with plasma (10%). Protein expression levels were determined using Western blot analyses and immunofluorescence staining, mRNA expression by quantitative reverse transcription-polymerase chain reaction, and the level of oxidative stress by dihydroethidium staining. Platelet adhesion, aggregation, and thrombin generation were determined. RESULTS: Increased plasma levels of interleukin (IL)-1ß, IL-6, tumor necrosis factor-α, monocyte chemoattractant protein-1, and soluble intercellular adhesion molecule-1 were observed in patients with COVID-19. Exposure of ECs to COVID-19 plasma with high cytokines levels induced redox-sensitive upregulation of SGLT2 expression via proinflammatory cytokines IL-1ß, IL-6, and tumor necrosis factor-α which, in turn, fueled endothelial dysfunction, senescence, NF-κB activation, inflammation, platelet adhesion and aggregation, von Willebrand factor secretion, and thrombin generation. The stimulatory effect of COVID-19 plasma was blunted by neutralizing antibodies against proinflammatory cytokines and empagliflozin. CONCLUSION: In patients with COVID-19, proinflammatory cytokines induced a redox-sensitive upregulation of SGLT2 expression in ECs, which in turn promoted endothelial injury, senescence, platelet adhesion, aggregation, and thrombin generation. SGLT2 inhibition with empagliflozin appeared as an attractive strategy to restore vascular homeostasis in COVID-19.

Outcomes of patients with active cancer undergoing transcatheter aortic valve replacement.

BACKGROUND: Cardiovascular disease and cancer are the two leading causes of mortality worldwide, and their association presents a therapeutic challenge. Current data regarding the prognosis of active cancer in patients undergoing transcatheter aortic valve replacement are conflicting. AIM: To determine the impact and prognosis of active cancer in transcatheter aortic valve replacement. METHODS: All consecutive patients with severe aortic stenosis treated by transcatheter aortic valve replacement between February 2010 and May 2019 were enrolled in a prospective study. The cohort was divided according to the presence or absence of active cancer at baseline. The primary endpoint was all-cause mortality 1 year after the procedure. RESULTS: A total of 1,125 patients were enrolled: 1,037 (92.2%) without and 88 (7.8%) with active cancer. The most frequent cancers were haematological (36.4%), breast (14.8%) and prostate (14.8%), with 79.5% of patients receiving curative treatment and 17.0% receiving palliative treatment. The 1-year mortality rate was higher in patients with active cancer (27.3% vs. 13.9%; P<0.01), mainly driven by non-cardiovascular causes. An increased cardiovascular mortality rate at 2 years was seen in patients with active cancer (27.5% vs. 15.0%; P=0.03) compared with a similar rate at 1-year follow-up. Active cancer was a strong predictor of 1-year all-cause mortality (hazard ratio 2.46, 95% confidence interval 1.19-4.68; P=0.02). Major/life-threatening bleeding events at 1 year were more frequent in patients with active cancer (P=0.02). CONCLUSIONS: Among patients who undergo transcatheter aortic valve replacement, 1-year all-cause mortality is higher in those with active cancer. We also observed a trend towards increased long-term bleeding events in case of active cancer.

Long-Term Survival Outcomes After Transcatheter Aortic Valve Replacement: A Real-World Experience of a Large Tertiary Center.

Transcatheter aortic valve replacement (TAVR) becomes the leading therapeutic choice for severe aortic stenosis. There is a growing body of knowledge on long-term survival outcomes, but available data from real-world observational studies are scarce. An observational cohort study was conducted on 705 consecutive patients who underwent TAVR at Strasbourg University Hospital between February 2010 and June 2017. We observed the living status (dead or alive) for each study participants by March 2023. The primary end point was to evaluate the all-cause mortality rate beyond 5 years after TAVR, compare the survival outcomes according to valve type, and identify predictors of mortality. Of the 705 study participants, 91.8% of the TAVR procedures were performed through the common femoral artery and 60.6% were treated with a balloon-expandable valve. Over a mean study period of 5.4 ± 3 years, the all-cause mortality rate was 45.8%. No difference in survival outcomes according to valve type was observed (p = 0.449). All-cause mortality rate was associated with age ≥90 years (hazard ratio [HR] 1.625, 1.109 to 2.380, p = 0.013), female gender (HR 0.228, 0.176 to 0.294, p <0.001), diabetes mellitus (HR 1.356, 1.070 to 1.719, p = 0.012), post-TAVR stroke (HR = 2.867, 1.690 to 4.865, p <0.001), and post-TAVR acute kidney injury (HR 1.977, 1.445 to 2.703, p <0.001). In conclusion, the present real-world large tertiary center experience showed that more than half of patients who underwent TAVR are alive beyond 5 years from procedure's date. All-cause mortality is mainly determined by advanced age and co-morbid conditions, and valve type has no advantage on the survival outcomes.

Bioprosthetic valve thrombosis after transcatheter aortic valve replacement and pulmonary embolism due to heparin-induced thrombocytopenia: a case report.

Background: Bioprosthetic valve thrombosis is a complication of transcatheter aortic valve replacement (TAVR). It is believed to be platelet independent, mainly driven by contact phase activation, and more likely to be targeted by oral anticoagulant (OAC). Case summary: We report case of an 86-year-old man with history of TAVR, who presented an early TAVR aortic valve thrombosis occurring in the context of heparin-induced thrombocytopenia (HIT) and pulmonary embolism. The patient rapidly recovered and was discharged 17 days after readmission. OAC by Coumadin was administered for 3 months. Chest tomography after 3 months showed the disappearance of the hypoattenuated leaflet thickening. Discussion: Although HIT has been fully described and is known for being a prothrombotic disorder, this is the first case report of aortic valve thrombosis after TAVR due to HIT. HIT is rare but possibly lethal. Diagnosis is based on pre-test probability evaluation with the 4T clinical score and confirmation with laboratory evidence of anti-PF4/heparin complexes and positivity of a functional test. Management of HIT is based on heparin discontinuation, and treatment of thrombotic complication with direct anti-IIa inhibitor or anti-Xa inhibitor. According to our knowledge, this case represents the first report of bioprosthetic valve thrombosis after TAVR due to HIT.

Determinants and treatments of heart failure after transcatheter aortic valve implantation: moving up a notch.

Transcatheter aortic valve implantation (TAVI) has become an alternative to surgical aortic valve replacement for patients with symptomatic severe aortic stenosis in elderly and comorbid population. Significant improvement in heart function has been observed in patients undergoing TAVI, but numerous patients are readmitted to hospital for heart failure (HF). Moreover, repeat HF hospitalization is strongly associated with an adverse prognosis and increases the financial burden of health care. Although studies have identified pre-existing and post-procedural factors that contribute to HF hospitalization after TAVI, there is a paucity of data regarding optimal post-procedural pharmacological treatments. This review aims to provide an overview of the current understanding of mechanisms, determinants, and potential treatments of HF following TAVI. We first review the pathophysiology of left ventricular (LV) remodelling, coronary microcirculation disorder, and endothelial dysfunction in patients with aortic stenosis and then examine the impact of TAVI on these conditions. We then present evidence of various factors and complications that may interplay with LV remodelling and contribute to HF events after TAVI. Next, we describe the triggers and predictors of early and late HF rehospitalizations following TAVI. Lastly, we discuss the potential of conventional pharmacological treatments, including renin-angiotensin blockers, beta-blockers, and diuretics in TAVI patients. The paper explores the potential of newer drugs, including sodium-glucose co-transporter 2 inhibitors, anti-inflammatory drugs, and ion supplementation. Comprehensive knowledge in this field may aid in recognizing successful existing therapies, developing effective new treatments, and establishing dedicated patient care strategies during follow-up after TAVI.

Occurrence of Severe Arrhythmias in Patients with Non-ST Elevation Acute Coronary Syndrome (NSTE-ACS): A Retrospective Study.

BACKGROUND: Non-ST elevation acute coronary syndrome (NSTE-ACS) is one of the most frequent manifestations of coronary artery disease. The occurrence of serious heart rhythm disorders (SHRDs) in NSTE-ACS is not well documented. However, continuous heart rhythm monitoring is recommended during the initial management of NSTE-ACS. The targeted monitoring of patients at greater risk for SHRDs could facilitate patients' care in emergency departments (EDs) where the flow of patients is continuously increasing. METHODS: This retrospective single-center study included 480 patients from emergency and cardiology departments within the Strasbourg University Hospital between 1 January 2019 and 31 December 2020. The objective was to estimate the frequency of the occurrence of SHRDs among patients with NSTE-ACS. The secondary objective was to highlight the factors associated with a higher risk of SHRDs. RESULTS: The proportion of SHRDs during the first 48 h of hospital care was 2.3% (CI95%: 1.2-4.1%, n = 11). Two time periods were considered: before coronary angiography (1.0%), and during, or after coronary angiography (1.3%). In the first group, two patients required immediate treatment (0.4% of the patients) and no death occurred. In the univariate analysis, the variables significantly associated with SHRDs were age, anticoagulant medication, a decrease in glomerular filtration rate, plasmatic hemoglobin, and left ventricle ejection fraction (LVEF), and an increase in plasmatic troponin, BNP, and CRP levels. In the multivariable analysis, plasmatic hemoglobin > 12 g/dL seemed to be a protective factor for SHRDs. CONCLUSIONS: In this study, SHRDs were rare and, most often, spontaneously resolved. These data challenge the relevance of systematic rhythm monitoring during the initial management of patients with NSTE-ACS.

Combination of Primary Hemostatic Disorders and Atrial Fibrillation Increases Bleeding Events Following Transcatheter Aortic Valve Replacement.

Background Patients with atrial fibrillation (AF) are likely to have a poor prognosis including bleedings following transcatheter aortic valve replacement (TAVR). Closure time of adenosine diphosphate (CT-ADP) is a primary hemostasis point-of-care test and is a predictor of bleeding events following TAVR. We aimed to evaluate the impact of ongoing primary hemostatic disorders on bleeding events in TAVR patients with AF. Methods We enrolled 878 patients from our prospective registry. The primary endpoint was VARC-2 major/life-threatening bleeding complications (MLBCs) at 1 year after TAVR and secondary endpoint was major adverse cardiac and cerebrovascular events (MACCEs) at 1 year, defined as a composite of all-cause death, myocardial infarction, stroke, and heart failure hospitalization. Ongoing primary hemostatic disorder was defined by a postprocedural CT-ADP >180 seconds. Results Patients with AF had a higher incidence of MLBCs (20 vs. 12%, p = 0.002), MACCE (29 vs. 20%, p = 0.002), and all-cause mortality (15 vs. 8%, p = 0.002) within 1 year compared to non-AF patients. When the cohort was split into four subgroups according to AF and CT-ADP >180 seconds, patients with AF and CT-ADP >180 seconds had the highest risk of MLBCs and MACCE. Multivariate Cox regression analysis confirmed that the patients with AF and CT-ADP >180 seconds had 3.9-fold higher risk of MLBCs, whereas those patients were no longer associated with MACCE after the adjustment. Conclusion In TAVR patients, AF with postprocedural CT-ADP >180 seconds was strongly associated with MLBCs following TAVR. Our study suggests that persistent primary hemostatic disorders contribute to a higher risk of bleeding events particularly in AF patients.

Coronary subclavian steal syndrome causing acute coronary syndrome: a case report.

Background: Myocardial infarction on non-occluded coronary artery represents a very specific subset of acute coronary syndrome (ACS). Coronary subclavian steal syndrome (CSSS) is defined by a left subclavian artery stenosis in case of (i) left internal mammary artery (LIMA) used to bypass left anterior descending artery (LAD) and (ii) >75% stenosis of the left subclavian artery prior to the origin of the LIMA to LAD graft. Here we report the case of a CSSS causing ACS. Case summary: A 71-year-old man with history of LIMA to LAD coronary artery bypass surgery was admitted to the nephrology intensive care unit for acute kidney injury requiring dialysis. Due to rapid deterioration, altered left ventricular ejection fraction and elevated c-troponin levels, an urgent coronary angiography was performed. It revealed a subtotal occlusion of the left subclavian artery prior to the origin of the LIMA to LAD graft. This was responsible for a severely altered coronary flow in the LIMA and LAD. Revascularization of the proximal left subclavian artery with a stent was performed, enabling instant recovery of distal coronary flows. Discussion: ACS due to CSSS in this report highlights the complexity of the cardio-renal interaction. Patients with coronary artery bypass graft and chronic kidney disease commonly exhibit a higher risk for severe progression of atherosclerosis at multiple sites. CSSS treatments include secondary prevention measures and revascularization (if indicated) such as an endovascular approach.

Baseline mean platelet volume is a strong predictor of major and life-threatening bleedings after transcatheter aortic valve replacement.

BACKGROUND: Bleeding following transcatheter aortic valve replacement (TAVR) has important prognostic implications. This study sought to evaluate the impact of baseline mean platelet volume (MPV) on bleeding events after TAVR. METHODS AND RESULTS: Patients undergoing TAVR between February 2010 and May 2019 were included. Low MPV (L-MPV) was defined as MPV ≤10 fL and high MPV (H-MPV) as MPV >10 fL. The primary endpoint was the occurrence of major/life-threatening bleeding complications (MLBCs) at one-year follow-up. Among 1,111 patients, 398 (35.8%) had L-MPV and 713 (64.2%) had H-MPV. The rate of MLBCs at 1 year was higher in L-MPV patients compared with H-MPV patients (22.9% vs. 17.7% respectively, p = 0.034). L-MPV was associated with vascular access-site complications (36.2% vs. 28.9%, p = 0.012), early (<30 days) major bleeding (15.6% vs. 9.4%, p<0.01) and red blood cell transfusion >2 units (23.9% vs. 17.5%, p = 0.01). No impact of baseline MPV on overall death, cardiovascular death and ischemic events (myocardial infarction and stroke) was evidenced. Multivariate analysis using Fine and Gray model identified preprocedural hemoglobin (sHR 0.84, 95%CI [0.75-0.93], p = 0.001), preprocedural L-MPV (sHR 1.64, 95%CI [1.16-2.32], p = 0.005) and closure time adenosine diphosphate post-TAVR (sHR 2.71, 95%CI [1.87-3.95], p<0.001) as predictors of MLBCs. CONCLUSIONS: Preprocedural MPV was identified as an independent predictor of MLBCs one year after TAVR, regardless of the extent of platelet inhibition and primary hemostasis disorders.

Acute kidney injury and acute kidney recovery following Transcatheter Aortic Valve Replacement.

BACKGROUND: Acute kidney injury (AKI) is associated with a dismal prognosis in Transcatheter Aortic Valve replacement (TAVR). Acute kidney recovery (AKR), a phenomenon reverse to AKI has recently been associated with better outcomes. METHODS: Between November 2012 to May 2018, we explored consecutive patients referred to our Heart Valve Center for TAVR. AKI was defined according to the VARC-2 definition. Mirroring the VARC-2 definition of AKI, AKR was defined as a decrease in serum creatinine (≥50%) or ≥25% improvement in GFR up to 72 hours after TAVR. RESULTS: AKI and AKR were respectively observed in 8.3 and 15.7% of the 574 patients included. AKI and AKR patients were associated to more advanced kidney disease at baseline. At a median follow-up of 608 days (range 355-893), AKI and AKR patients experienced an increased cardiovascular mortality compared to unchanged renal function patients (14.6% and 17.8% respectively, vs. 8.1%, CI 95%, p<0.022). Chronic kidney disease, (HR: 3.9; 95% CI 1.7-9.2; p < 0.001) was the strongest independent factor associated with AKI similarly to baseline creatinine level (HR: 1; 95% CI 1 to 1.1 p < 0.001) for AKR. 72-hours post procedural AKR (HR: 2.26; 95% CI 1.14 to 4.88; p = 0.021) was the strongest independent predictor of CV mortality. CONCLUSIONS: Both AKR and AKI negatively impact long term clinical outcomes of patients undergoing TAVR.

Incomplete Recovery From Takotsubo Syndrome Is a Major Determinant of Cardiovascular Mortality.

BACKGROUND: Although there is an apparent rapid and spontaneous recovery of left ventricular ejection fraction (LVEF) in patients with Takotsubo syndrome (TTS), recent studies have demonstrated a long-lasting functional impairment in those patients. The present study sought to evaluate the predictors of incomplete recovery following TTS and its impact on cardiovascular mortality.Methods and Results:Patients with TTS between 2008 and 2018 were retrospectively enrolled at 3 different institutions. After exclusion of in-hospital deaths, 407 patients were split into 2 subgroups according to whether their LVEF was >50% (recovery group; n=341), or ≤50% (incomplete recovery group; n=66) at the chronic phase. Multivariate logistic regression analysis found that LVEF (odds ratio [OR]: 0.94; 95% confidence interval [CI]: 0.91-0.98; P<0.001) and C-reactive protein levels (OR: 1.11; 95% CI: 1.02-1.22; P=0.02) at discharge were independent predictors of incomplete recovery. At a median follow up of 52 days, a higher cardiovascular mortality was evident in the incomplete recovery group (16% vs. 0.6%; P<0.001). CONCLUSIONS: This study demonstrated that incomplete recovery after TTS is characterized by residual systemic inflammation and an increased cardiac mortality at follow up. Altogether, the present study findings determined that patients with persistent inflammation are a high-risk subgroup, and should be targeted in future clinical trials with specific therapies to attenuate inflammation.

Electrocardiographic Strain Pattern Is a Major Determinant of Rehospitalization for Heart Failure After Transcatheter Aortic Valve Replacement.

Background Electrocardiographic strain pattern (ESP) has recently been associated with increased adverse outcome in aortic stenosis and after surgical aortic valve replacement. Our study sought to determine the impact and incremental value of ESP pattern in predicting adverse outcome after transcatheter aortic valve replacement. Methods and Results A total of 585 patients with severe aortic stenosis (mean age, 83±7 years; men, 39.8%) were enrolled for transcatheter aortic valve replacement from November 2012 to May 2018. ESP was defined as ≥1-mm concave down-sloping ST-segment depression and asymmetrical T-wave inversion in the lateral leads. The primary end points of the study were all-cause mortality, rehospitalization for heart failure, myocardial infarction, and stroke. A total of 178 (30.4%) patients were excluded because of left bundle-branch block (n=103) or right bundle-branch block (n=75). Among the 407 remaining patients, 106 had ESP (26.04%). At a median follow-up of 20.00 months (11.70-29.42 months), no impact of electric strain on overall and cardiac death could be established. By contrast, incidence of rehospitalization for heart failure was significantly higher (33/106 [31.1%] versus 33/301 [11%]; P<0.001) in patients with ESP. By multivariate analyses, ESP remained a strong predictor of rehospitalization for heart failure (hazard ratio, 2.75 [95% CI, 1.61-4.67]; P<0.001). Conclusions In patients with aortic stenosis who were eligible for transcatheter aortic valve replacement, ESP is frequent and associated with an increased risk of postinterventional heart failure regardless of preoperative left ventricular hypertrophy. ESP represents an easy, objective, reliable, and low-cost tool to identify patients who may benefit from intensified postinterventional follow-up.

Impact of Primary Hemostasis Disorders on Late Major Bleeding Events among Anticoagulated Atrial Fibrillation Patients Treated by TAVR.

BACKGROUND: Bleeding events are among the striking complications following transcatheter aortic valve replacement (TAVR), and bleeding prediction models are crucially warranted. Several studies have highlighted that primary hemostasis disorders secondary to persistent loss of high-molecular-weight (HMW) multimers of the von Willebrand factor (vWF) and assessed by adenosine diphosphate closure time (CT-ADP) may be a strong predictor of late major/life-threatening bleeding complications (MLBCs). Pre-existing atrial fibrillation (AF) is a frequent comorbidity in TAVR patients and potentially associated with increased bleeding events after the procedure. OBJECTIVES: This study evaluated the impact of ongoing primary hemostasis disorders, as assessed by post-procedural CT-ADP > 180 s, on clinical events after TAVR among anticoagulated AF patients. METHODS: An ongoing primary hemostasis disorder was defined by post-procedure CT-ADP > 180 s. Bleeding complications were assessed according to the Valve Academic Research Consortium-2 (VARC-2) criteria. The primary endpoint was the occurrence of late MLBCs at one-year follow-up. The secondary endpoint was a composite of mortality, stroke, myocardial infarction, and rehospitalization for heart failure. RESULTS: In total, 384 TAVR patients were included in the analysis. Of these patients, 57 patients (14.8%) had a prolongated CT-ADP > 180 s. Increased MLBCs were observed in patients with CT-ADP > 180 s (35.1% versus 1.2%; p < 0.0001). Conversely, the occurrence of the composite endpoint did not differ between the groups. Multivariate analysis identified CT-ADP > 180 s (HR 28.93; 95% CI 9.74-85.95; p < 0.0001), bleeding history, paradoxical aortic stenosis (AS), and major vascular complications following TAVR as independent predictors of late MLBCs. CONCLUSION: Among patients with anticoagulated AF, a post-procedural CT-ADP > 180 s was identified as a strong independent predictor of late MLBCs. These findings suggest that persistent primary hemostasis disorders contribute to a higher risk of late bleeding events and should be considered for a tailored, risk-adjusted antithrombotic therapy after TAVR.