Leaflet modification before transcatheter aortic valve implantation in patients at risk for coronary obstruction: the ShortCut study.

BACKGROUND AND AIMS: This trial sought to assess the safety and efficacy of ShortCut, the first dedicated leaflet modification device, prior to transcatheter aortic valve implantation (TAVI) in patients at risk for coronary artery obstruction. METHODS: This pivotal prospective study enrolled patients with failed bioprosthetic aortic valves scheduled to undergo TAVI and were at risk for coronary artery obstruction. The primary safety endpoint was procedure-related mortality or stroke at discharge or 7 days, and the primary efficacy endpoint was per-patient leaflet splitting success. Independent angiographic, echocardiographic, and computed tomography core laboratories assessed all images. Safety events were adjudicated by a clinical events committee and data safety monitoring board. RESULTS: Sixty eligible patients were treated (77.0 ± 9.6 years, 70% female, 96.7% failed surgical bioprosthetic valves, 63.3% single splitting and 36.7% dual splitting) at 22 clinical sites. Successful leaflet splitting was achieved in all (100%; 95% confidence interval [CI] 94-100.0%, p<0.001) patients. Procedure time, including imaging confirmation of leaflet splitting, was 30.6 ± 17.9 min. Freedom from the primary safety endpoint was achieved in 59 (98.3%; 95% CI [91.1-100%]) patients, with no mortality and one (1.7%) disabling stroke. At 30 days, freedom from coronary obstruction was 95% (95% CI 86.1-99.0%). Within 90 days, freedom from mortality was 95% (95% CI 86.1-99.0%]), without any cardiovascular deaths. CONCLUSIONS: Modification of failed bioprosthetic aortic valve leaflets using ShortCut was safe, achieved successful leaflet splitting in all patients, and was associated with favorable clinical outcomes in patients at risk for coronary obstruction undergoing TAVI.

Critically ill patients with infective endocarditis, neurological complications and indication for cardiac surgery: a multicenter propensity-adjusted study.

BACKGROUND: The benefit-risk balance and optimal timing of surgery for severe infective endocarditis (IE) with ischemic or hemorrhagic strokes is unknown. The study aim was to compare the neurological outcome between patients receiving surgery or not. METHODS: In a prospective register-based multicenter ICU study, patients were included if they met the following criteria: (i) left-sided IE with an indication for heart surgery; (ii) with cerebral complications documented by cerebral imaging before cardiac surgery; (iii) with Sequential Organ Failure Assessment score ≥ 3. Exclusion criteria were isolated right-sided IE, in-hospital acquired IE and patients with cerebral complications only after cardiac surgery. In the primary analysis, the prognostic value of surgery in term of disability at 6 month was assessed by using a propensity score-adjusted logistic regression. RESULTS: 192 patients were included including ischemic stroke (74.5%) and hemorrhagic lesion (15.6%): 67 (35%) had medical treatment and 125 (65%) cardiac surgery. In the propensity score-adjusted logistic regression, a favorable 6-month neurological outcome was associated with surgery (odds ratio 13.8 (95% CI 6.2-33.7). The 1-year mortality was strongly reduced with surgery in the fixed-effect propensity-adjusted Cox model (hazard ratio 0.18; 95% CI 0.11-0.27; p < 0.001). These effects remained whether the patients received delayed surgery (n = 62/125) or not and whether they were deeply comatose (Glasgow Coma Scale ≤ 10) or not. CONCLUSIONS: In critically ill IE patients with an indication for surgery and previous cerebral events, a better propensity-adjusted neurological outcome was associated with surgery compared with medical treatment.

Systematic Aetiological Assessment of Myocarditis: A Prospective Cohort Study.

BACKGROUND: Myocarditis is commonly diagnosed in the intensive care cardiology unit (ICCU). No current recommendation nor guideline aids exist for aetiological assessments. METHODS: From September 2021 to October 2023, 84 patients with acute myocarditis underwent thorough and systematic serum and blood cell panel evaluations to determine the most common causes of myocarditis. RESULTS: Of the 84 patients (median age 34 years, range 22-41 years, 79% male), 16 presented with complicated myocarditis. The systematic aetiological assessment revealed that 36% of patients were positive for lupus anticoagulant, 12% for antinuclear antibodies, 8% for anti-heart antibodies, and 12% for anti-striated muscle antibodies. Viral serology did not yield any significant results. After the aetiological assessment, one patient was diagnosed with an autoimmune inflammatory disorder (Still's disease). T-cell subset analyses indicated that myocarditis severity tended to increase with the T-cell lymphopenia status. CONCLUSIONS: A comprehensive, systematic aetiological assessment was of limited value in terms of predicting the clinical or therapeutic outcomes in myocarditis patients presenting to the ICCU.

Impact of Valve Academic Research Consortium 3 (VARC-3) minor access site vascular complications in patients undergoing percutaneous transfemoral transcatheter aortic valve implantation.

OBJECTIVES: The aim of this study was to investigate the impact of Valve Academic Research Consortium 3 minor access site vascular complications (VCs) in patients who underwent percutaneous transfemoral (TF) transcatheter aortic valve implantation (TAVI). METHODS: This single-centre retrospective study included consecutive patients who underwent percutaneous TF-TAVI from 2009 to 2021. A propensity score-matched analysis was performed to compare early and long-term clinical results between patients with VC and without VC (nVC). RESULTS: A total of 2161 patients were included, of whom 284 (13.1%) experienced access site VC. Propensity score analysis allowed to match 270 patients from the VC group with 727 patients from the nVC group. In the matched cohorts, the VC group showed longer operative times (63.5 vs 50.0 min, P < 0.001), higher operative and in-hospital mortality (2.6% vs 0.7%, P = 0.022; and 6.3% vs 3.2%, P = 0.040, respectively), longer hospital length of stay (8 vs 7 days, P = 0.001) and higher rates of blood transfusion (20.4% vs 4.3%, P < 0.001) and infectious complications (8.9% vs 3.8%, P = 0.003). Overall survival during follow-up was significantly lower in the VC group (hazard ratio 1.37, 95% CI 1.03-1.82, P = 0.031) with 5-year survival rates being 58.0% (95% CI 49.5-68.0%) and 70.7% (95% CI 66.2-75.5%) for the VC and nVC groups, respectively. CONCLUSIONS: This retrospective study observed that minor access site VCs during percutaneous TF-TAVI can be serious events affecting early and long-term outcomes.

Glycaemic Variability and Hyperglycaemia as Prognostic Markers of Major Cardiovascular Events in Diabetic Patients Hospitalised in Cardiology Intensive Care Unit for Acute Heart Failure.

(1) Background: Hyperglycaemia and hypoglycaemia are both emerging risk factors for cardiovascular disease. Nevertheless, the potential effect of glycaemic variability (GV) on mid-term major cardiovascular events (MACE) in diabetic patients presenting with acute heart failure (AHF) remains unclear. This study investigates the prognostic value of GV in diabetic patients presenting with acute heart failure (AHF). (2) Methods: this was an observational study including consecutive patients with diabetes and AHF between January 2015 and November 2016. GV was calculated using standard deviation of glycaemia values during initial hospitalisation in the intensive cardiac care unit. MACE, including recurrent AHF, new-onset myocardial infarction, ischaemic stroke and cardiac death, were recorded. The predictive effects of GV on patient outcomes were analysed with respect to baseline characteristics and cardiac status. (3) Results: In total, 392 patients with diabetes and AHF were enrolled. During follow-up (median (interquartile range) 29 (6−51) months), MACE occurred in 227 patients (57.9%). In total, 92 patients died of cardiac causes (23.5%), 107 were hospitalised for heart failure (27.3%), 19 had new-onset myocardial infarction (4.8%) and 9 (2.3%) had an ischaemic stroke. Multivariable logistic regression analysis showed that GV > 50 mg/dL (2.70 mmol/L), age > 75 years, reduced left ventricular ejection fraction (LVEF < 30%) and female gender were independent predictors of MACE: hazard ratios (HR) of 3.16 (2.25−4.43; p < 0.001), 1.54 (1.14−2.08; p = 0.005), 1.47 (1.06−2.07; p = 0.02) and 1.43 (1.05−1.94; p = 0.03), respectively. (4) Conclusions: among other well-known factors of HF, a GV cut-off value of >50 mg/dL was the strongest independent predictive factor for mid-term MACE in patients with diabetes and AHF.

Brain imaging determinants of functional prognosis after severe endocarditis: a multicenter observational study.

OBJECTIVE: We developed a detailed imaging phenotype of the cerebral complications in critically ill patients with infective endocarditis (IE) and determine whether any specific imaging pattern could impact prognostic information. METHODS: One hundred ninety-two patients admitted to the intensive care units of seven tertiary centers with severe, definite left IE and neurological complications were included. All underwent cerebral imaging few days after admission to define the types of lesions, their volumes, and their locations using voxel-based lesion-symptom mapping (VLSM). We employed uni- and multi-variate logistic regression analyses to explore the associations among imaging features and other prognostic variables and the 6-month modified Rankin Scale (mRS) score. RESULTS: Ischemic lesions were the most common lesions (75%; mean volume, 15.3 ± 33 mL) followed by microbleeds (50%; mean number, 4 ± 7.5), subarachnoidal hemorrhages (20%), hemorrhagic strokes (16%; mean volume, 14.6 ± 21 mL), and hemorrhagic transformations (10%; mean volume, 5.6 ± 11 mL). The volume of hemorrhagic transformations, the severity of leukopathy, and the compromises of certain locations on the motor pathway from the VLSM were associated with a poor 6-month mRS score on univariate analyses. However, upon multivariate analyses, no such specific imaging pattern independently predicted the mRS; this was instead influenced principally by age (OR = 1.03 [1.004-1.06]) and cardiac surgery status (OR = 0.06 [0.02-0.16]) in the entire cohort, and by age (OR = 1.04 [1.01-1.08]) and Staphylococcus aureus status (OR = 2.86 [1.19-6.89]) in operated patients. CONCLUSIONS: In a cohort of severely ill IE patients with neurological complications, no specific imaging pattern could be highlighted as a reliable predictor of prognosis.

Bail-out therapy in ST-segment elevation myocardial infarction due to calcified lesion causing stent underexpansion: Intravascular lithotripsy is in the lead.

A 52-year-old male was referred for an acute anterior ST-segment elevation myocardial infarction (STEMI). Coronary angiography revealed an acute left anterior descending artery occlusion. The patient was treated with a drug-eluting stent (DES). Despite long and repeated high-pressure inflations (>20 atm) of non-compliant balloons, OPN NCⓇ high-pressure balloon (SIS Medical AG; Frauenfeld, Switzerland), rotational atherectomy, and cutting balloon, there was a severe hourglass stent underexpansion caused by coronary calcification. Thus, intravascular lithotripsy (IVL) (Shockwave Medical, Fremont, CA, USA) was attempted to re-dilate this calcified lesion. Underexpansion was successfully treated after delivering 70 shockwaves to the narrowest segment. IVL delivers localized pulsatile sonic pressure waves inducing circumferential calcium modification and multiple fractures. Our observation illustrates the additional value of coronary lithotripsy as a bail-out procedure to tackle severely calcified, de novo coronary lesions causing stent underexpansion in the context of STEMI, when all other available techniques failed. .

OCT and CMR for the Diagnosis of Patients Presenting With MINOCA and Suspected Epicardial Causes.

OBJECTIVES: Among all patients presenting with myocardial infarction with nonobstructive coronary arteries (MINOCA), epicardial causes may be suspected when there is a correlation between electrocardiogram (ECG) changes and regional wall motion abnormalities (WMAs). We evaluated the diagnostic yield of intravascular optical coherence tomography (OCT) and cardiac magnetic resonance (CMR) in this specific setting. BACKGROUND: OCT is able to identify different morphologic features of coronary plaques that are well known causes of MINOCA. Furthermore, CMR has become the gold standard for detection of myocardial infarction in the setting of MINOCA. METHODS: In a prospective 2-center study, consecutive patients with MINOCA including ECG features of ischemia associated with corresponding WMAs underwent OCT and CMR. RESULTS: Forty patients (mean age: 50 ± 11 years, 62.5% male, 32.5% with ST-segment elevation) were enrolled. Coronary arteries were normal on coronary angiography in 10 patients (25%); 18 patients (45%) presented minimal lumen irregularities, whereas the remaining 12 patients (30%) showed mild to moderate (≥30% but <50%) coronary lesions. Plaque rupture, eruptive calcific nodule, plaque erosion, lone thrombus, and spontaneous coronary artery dissection were found in 14 (35%), 1 (2.5%), 12 (30%), 3 (7.5%), and 2 (5%) patients, respectively. Acute myocardial infarction was evident at CMR in 31 of 40 patients (77.5%). Twenty-three patients (57.5%) had a substrate and/or diagnosis supported by both techniques with an evident relationship between the findings obtained by the 2 techniques. By coupling OCT with CMR, a substrate and/or diagnosis was found in 100% of cases. CONCLUSIONS: OCT coupled with CMR can provide a clear substrate and/or diagnosis in the vast majority of patients presenting with MINOCA including ECG features of ischemia associated with corresponding WMAs.

Guidance of the MitraClip® procedure by 2D and 3D imaging.

Percutaneous edge-to-edge repair using MitraClip® (Abbott Laboratories, Abbott Park, IL, USA) can be used to treat mitral regurgitation. However, real-time echocardiographic guidance is vital; and use of 3D transoesophageal echocardiography to guide the procedure has improved reproducibility, reliability and safety. This review describes the MitraClip® device - which is composed of a steerable guide catheter (SGC) and a Clip Delivery System (CDS) - and the MitraClip® procedure. The procedure consists of six steps: (1) transseptal approach and puncture; (2) introduction of the SGC into the left atrium; (3) navigation with the CDS into the left atrium to place the MitraClip® above the mitral valve; (4) crossing the valve and advancing the CDS into the left ventricle; (5) grasping the leaflets and assessment of the quality of the grasping; and (6) final mitral regurgitation assessment. This review also describes which imaging techniques are applicable to each stage of the procedure; and contains examples of the various images obtained during these steps.

Planar cell polarity genes frizzled4 and frizzled6 exert patterning influence on arterial vessel morphogenesis.

Quantitative analysis of the vascular network anatomy is critical for the understanding of the vasculature structure and function. In this study, we have combined microcomputed tomography (microCT) and computational analysis to provide quantitative three-dimensional geometrical and topological characterization of the normal kidney vasculature, and to investigate how 2 core genes of the Wnt/planar cell polarity, Frizzled4 and Frizzled6, affect vascular network morphogenesis. Experiments were performed on frizzled4 (Fzd4-/-) and frizzled6 (Fzd6-/-) deleted mice and littermate controls (WT) perfused with a contrast medium after euthanasia and exsanguination. The kidneys were scanned with a high-resolution (16 µm) microCT imaging system, followed by 3D reconstruction of the arterial vasculature. Computational treatment includes decomposition of 3D networks based on Diameter-Defined Strahler Order (DDSO). We have calculated quantitative (i) Global scale parameters, such as the volume of the vasculature and its fractal dimension (ii) Structural parameters depending on the DDSO hierarchical levels such as hierarchical ordering, diameter, length and branching angles of the vessel segments, and (iii) Functional parameters such as estimated resistance to blood flow alongside the vascular tree and average density of terminal arterioles. In normal kidneys, fractal dimension was 2.07±0.11 (n = 7), and was significantly lower in Fzd4-/- (1.71±0.04; n = 4), and Fzd6-/- (1.54±0.09; n = 3) kidneys. The DDSO number was 5 in WT and Fzd4-/-, and only 4 in Fzd6-/-. Scaling characteristics such as diameter and length of vessel segments were altered in mutants, whereas bifurcation angles were not different from WT. Fzd4 and Fzd6 deletion increased vessel resistance, calculated using the Hagen-Poiseuille equation, for each DDSO, and decreased the density and the homogeneity of the distal vessel segments. Our results show that our methodology is suitable for 3D quantitative characterization of vascular networks, and that Fzd4 and Fzd6 genes have a deep patterning effect on arterial vessel morphogenesis that may determine its functional efficiency.

Lethal Aorto-Right Ventricular Defect After Transcatheter Aortic Valve Implantation in a Patient With Radiation-Induced Porcelain Aorta: Notes of Caution.

A 47-year-old man with severe radiation-induced aortic stenosis was rejected for cardiac surgery because of porcelain aorta. We successfully implanted an Edwards SAPIEN valve (Edwards Lifesciences, Irvine, CA), but the patient was readmitted 3 weeks later for heart failure with a continuous murmur on auscultation. Echocardiography showed a small defect between the aorta and the infundibulum of the right ventricle, which was also confirmed with aortography and computed tomography. Medical therapy was optimized; however, he died unexpectedly a few weeks later. We concluded that irradiated tissues are particularly fragile and require specific attention during transcatheter aortic valve implantation. Furthermore, this case suggests that a more aggressive closure should have been applied.

The use of Impella 2.5 in severe refractory cardiogenic shock complicating an acute myocardial infarction.

OBJECTIVES: To investigate the outcome of patients with acute myocardial infarction (AMI) complicated by refractory cardiogenic shock (CS) who underwent mechanical circulatory support with Impella 2.5. BACKGROUND: AMI complicated by CS remains a highly fatal condition. A potent and minimally invasive left ventricular assist device might improve patient outcomes. METHODS: We analyzed the procedural characteristics and outcomes of 22 consecutive patients who underwent, between July 2008 and December 2012, a percutaneous coronary intervention and Impella 2.5 support for AMI complicated by CS refractory to first-line therapy with inotropes and/or Intra-aortic balloon pump. RESULTS: In this analysis, patients were relatively young with a mean age of 57.9 ± 11.6 year old and 59.1% were male. The majority of patients (77.3%) were admitted in CS and 40.9% sustained cardiac arrest prior to admission. Hemodynamics improved significantly upon initiation of support, end-organ and tissue perfusion improved subsequently demonstrated by a significant decrease in lactate levels from 6.37 ± 5.3 mmol/L to 2.41 ± 2.1 mmo/L, (P = 0.008) after 2 days of support. Thirteen (59.1%) patients were successfully weaned-off Impella 2.5 and 4 (18.2%) were transitioned to another device. We observed a functional recovery of the left ventricle when compared to baseline (43 ± 10% vs. 27 ± 9%, P < 0.0001). The survival rate at 6 months and 1 year was 59.1% and 54.5%, respectively. CONCLUSION: Impella 2.5 was initiated as a last resort therapy to support very sick patients with refractory CS after failed conventional therapy. The use of the device yielded favorable short and mid-term survival results with recovery being the most frequently observed outcome.

Hypoxia preconditioned mesenchymal stem cells improve vascular and skeletal muscle fiber regeneration after ischemia through a Wnt4-dependent pathway.

Mesenchymal stem cells (MSC) are multipotent postnatal stem cells, involved in the treatment of ischemic vascular diseases. We investigate the ability of MSC, exposed to short-term hypoxic conditions, to participate in vascular and tissue regeneration in an in vivo model of hindlimb ischemia. Transplantation of hypoxic preconditioned murine MSC (HypMSC) enhanced skeletal muscle regeneration at day 7, improved blood flow and vascular formation compared to injected nonpreconditioned MSC (NormMSC). These observed effects were correlated with an increase in HypMSC engraftment and a putative role in necrotic skeletal muscle fiber clearance. Moreover, HypMSC transplantation resulted in a large increase in Wnt4 (wingless-related MMTV integration site 4) expression and we demonstrate its functional significance on MSC proliferation and migration, endothelial cell (EC) migration, as well as myoblast differentiation. Furthermore, suppression of Wnt4 expression in HypMSC, abrogated the hypoxia-induced vascular regenerative properties of these cells in the mouse hindlimb ischemia model. Our data suggest that hypoxic preconditioning plays a critical role in the functional capabilities of MSC, shifting MSC location in situ to enhance ischemic tissue recovery, facilitating vascular cell mobilization, and skeletal muscle fiber regeneration via a paracrine Wnt-dependent mechanism.