Impact of anaemia and iron deficiency on outcomes in cardiogenic shock complicating acute myocardial infarction.

AIMS: Anaemia and iron deficiency (ID) are common comorbidities in cardiovascular patients and are associated with a poor clinical status, as well as a worse outcome in patients with heart failure and acute myocardial infarction (AMI). Nevertheless, data concerning the impact of anaemia and ID on clinical outcomes in patients with cardiogenic shock (CS) are scarce. This study aimed to assess the impact of anaemia and ID on clinical outcomes in patients with CS complicating AMI. METHODS AND RESULTS: The presence of anaemia (haemoglobin <13 g/dl in men and <12 g/dl in women) or ID (ferritin <100 ng/ml or transferrin saturation <20%) was determined in patients with CS due to AMI from the CULPRIT-SHOCK trial. Blood samples were collected in the catheterization laboratory during initial percutaneous coronary intervention. Clinical outcomes were compared in four groups of patients having neither anaemia nor ID, against patients with anaemia with or without ID and patients with ID only. A total of 427 CS patients were included in this analysis. Anaemia without ID was diagnosed in 93 (21.7%), anaemia with ID in 54 study participants (12.6%), ID without anaemia in 72 patients (16.8%), whereas in 208 patients neither anaemia nor ID was present (48.9%). CS patients with anaemia without ID were older (73 ± 10 years, p = 0.001), had more frequently a history of arterial hypertension (72.8%, p = 0.01), diabetes mellitus (47.8%, p = 0.001), as well as chronic kidney disease (14.1%, p = 0.004) compared to CS patients in other groups. Anaemic CS patients without ID presence were at higher risk to develop a composite from all-cause death or renal replacement therapy at 30-day follow-up (odds ratio [OR] 3.83, 95% confidence interval [CI] 2.23-6.62, p < 0.001) than CS patients without anaemia/ID. The presence of ID in CS patients, with and without concomitant anaemia, did not increase the risk for the primary outcome (OR 1.17, 95% CI 0.64-2.13, p = 0.64; and OR 1.01, 95% CI 0.59-1.73, p = 0.54; respectively) within 30 days of follow-up. In time-to-event Kaplan-Meier analysis, anaemic CS patients without ID had a significantly higher hazard ratio (HR) for the primary outcome (HR 2.11, 95% CI 1.52-2.89, p < 0.001), as well as for death from any cause (HR 1.90, 95% CI 1.36-2.65, p < 0.001) and renal replacement therapy during 30-day follow-up (HR 2.99, 95% CI 1.69-5.31, p < 0.001). CONCLUSION: Concomitant anaemia without ID presence in patients with CS at hospital presentation is associated with higher risk for death from any cause or renal replacement therapy and the individual components of this composite endpoint within 30 days after hospitalization. ID has no relevant impact on clinical outcomes in patients with CS.

Comparison of plug-based versus suture-based vascular closure for large-bore arterial access: a collaborative meta-analysis of observational and randomized studies.

BACKGROUND: Large-bore arteriotomies can be percutaneously closed with suture-based or plug-based vascular closure device (VCD) strategies. The efficacy of both techniques remains controversial. AIMS: We conducted a meta-analysis of comparative studies between both VCD strategies, focusing on the most commonly applied VCDs (MANTA and ProGlide). METHODS: We searched MEDLINE, the Cochrane Central Register of Controlled Trials and Google scholar for observational studies (OS) and randomized controlled trials (RCT) comparing vascular closure with the MANTA-based and the ProGlide-based technique. The principal endpoint of this analysis was access-site related vascular complications. Both study types were analyzed separately. RESULTS: Access-site related vascular complications were less frequent after vascular closure with the MANTA technique in the analysis of OS (RR 0.61 [95%CI 0.43-0.89], p = 0.01, I2 = 0%), but more frequent in the analysis of RCT data (RR 1.70 [95%CI 1.16-2.51], p = 0.01, I2 = 0%). Both data sets provided no significant difference between the VCD techniques in terms of overall bleeding events (OS: RR 0.57 [95%CI 0.32-1.02], p = 0.06, I2 = 70%; and RCT: RR 1.37 [95%CI 0.82-2.28], p = 0.23, I2 = 30%). RCT data showed that endovascular stenting or vascular surgery due to VCD failure occurred more often after MANTA application (RR 3.53 [95%CI 1.07-11.33], p = 0.04, I2 = 0%). CONCLUSIONS: While OS point to favorable outcomes for large-bore vascular closure with the MANTA-based technique, RCT data show that this strategy is associated with more access-site related vascular complications as well as endovascular stenting or vascular surgery due to device failure compared with the ProGlide-based technique.

Balloon-assisted injection of fibrin sealant for the treatment of postintervention access-site bleeding complications.

This study sought to evaluate a new method that uses injection of fibrin sealant under simultaneous balloon occlusion for the treatment of postinterventional access site bleeding complications. With the rising complexity of interventional procedures, iatrogenic false aneurysms and active bleeding has become more common. In general, these complications are associated with increased morbidity and mortality, especially if surgical repair is required. Although high success rates are reported for ultrasound-guided compression and ultrasound-guided thrombin injection, these methods are not always feasible. All procedures of fibrin sealant injection under simultaneous balloon occlusion for the treatment of postinterventional access site bleeding complications or pseudoaneurysm were prospectively collected. Additional data were retrospectively obtained and analyzed for all patients treated by this new method. In total, 53 patients were included from 2018 to 2021. Most of the access site complications were related to transcatheter aortic valve replacement (40%) or percutaneous coronary intervention (21%), but also to a wide variety of other procedures. Of the 53 patients, 30 had to be treated for false aneurysms and 23 for active bleeding. A high primary success rate of 94% was achieved. Recurrences of false aneurysms occurred in six patients, of which only one needed open surgical repair. Regarding complications, two peripheral embolisms, thereof one requiring additional stent implantation occurred. Balloon-assisted thrombin injection seems to be feasible and safe. It provides a new alternative to prevent surgery for patients where common techniques are unavailable or have failed.

The novel cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide (CLIP)-based mortality risk score in cardiogenic shock after acute myocardial infarction.

BACKGROUND: Cardiogenic shock (CS) complicating acute myocardial infarction (AMI) still reaches excessively high mortality rates. This analysis is aimed to develop a new easily applicable biomarker-based risk score. METHODS AND RESULTS: A biomarker-based risk score for 30-day mortality was developed from 458 patients with CS complicating AMI included in the randomized CULPRIT-SHOCK trial. The selection of relevant predictors and the coefficient estimation for the prognostic model were performed by a penalized multivariate logistic regression analysis. Validation was performed internally, internally externally as well as externally in 163 patients with CS included in the randomized IABP-SHOCK II trial. Blood samples were obtained at randomization. The two trials are registered with ClinicalTrials.gov (NCT01927549 and NCT00491036), are closed to new participants, and follow-up is completed. Out of 58 candidate variables, the four strongest predictors for 30-day mortality were included in the CLIP score (cystatin C, lactate, interleukin-6, and N-terminal pro-B-type natriuretic peptide). The score was well calibrated and yielded high c-statistics of 0.82 [95% confidence interval (CI) 0.78-0.86] in internal validation, 0.82 (95% CI 0.75-0.89) in internal-external (temporal) validation, and 0.73 (95% CI 0.65-0.81) in external validation. Notably, it outperformed the Simplified Acute Physiology Score II and IABP-SHOCK II risk score in prognostication (0.83 vs 0.62; P < 0.001 and 0.83 vs. 0.76; P = 0.03, respectively). CONCLUSIONS: A biomarker-only score for 30-day mortality risk stratification in infarct-related CS was developed, extensively validated and calibrated in a prospective cohort of contemporary patients with CS after AMI. The CLIP score outperformed other clinical scores and may be useful as an early decision tool in CS.

Impact of smoking on cardiac magnetic resonance infarct characteristics and clinical outcome in patients with non-ST-elevation myocardial infarction.

Data derived from several studies suggest a better survival in smokers with acute myocardial infarction, a phenomenon referred to as the 'smoker's paradox'. We aimed to investigate the association of smoking with cardiac magnetic resonance (CMR) imaging determined infarct severity and major adverse cardiac events (MACE) defined as the occurrence of death, reinfarction, and congestive heart failure at 12 months in patients with non-ST-elevation myocardial infarction (NSTEMI) reperfused by early percutaneous coronary intervention (PCI). In this multicenter, registry study 311 NSTEMI patients underwent CMR imaging 3 (interquartile range [IQR] 2-4) days after PCI. Myocardial salvage index (MSI), infarct size (IS), and microvascular obstruction (MVO) as well as MACE rate were compared according to admission smoking status. Approximately one-third of patients were current smokers (n = 122, 39%). Smokers were significantly younger and less likely to have hypertension as compared to non-smokers (all p < 0.05). The extent of MSI (63.2, IQR 28.9-85.4 vs. 65.6, IQR 42.2-82.9, p = 0.30), and IS (7.2, IQR 2.3-15.7%LV vs. 7.0, IQR 2.2-12.4%LV, p = 0.27) did not differ significantly between smokers and non-smokers. Despite similar prevalence of MVO, MVO (%LV) was higher in smokers compared to non-smokers (2.0, IQR 0.9-4.7%LV vs. 1.2, IQR 0.7-2.2%LV, p = 0.03). MACE rates at 12 months were comparable in smokers and non-smokers (5.7% vs. 7.4%, p = 0.65). In NSTEMI patients, smoking is neither associated with increased myocardial salvage nor less severe myocardial damage. Clinical outcome at 12 months was similar in smokers and non-smokers.Trial registration NCT03516578.

Safety and efficacy of persistent atrial fibrillation ablation using the second-generation cryoballoon.

BACKGROUND: The second-generation cryoballoon (CB) is increasingly used for treatment of persistent atrial fibrillation (AF). Data regarding the clinical outcome and mechanism of arrhythmia recurrence following persistent AF ablation using CB is sparse. In this study, we aimed to assess the efficacy of CB and mechanisms of atrial tachyarrhythmia (ATA) recurrence in patients with persistent AF. METHODS AND RESULTS: A total of 133 patients (66 ± 10 years, 60% male) with symptomatic persistent AF, who were scheduled for PVI using the second-generation CB were enrolled. Follow-up included 24 h Holter recording at 3, 6 and 12 months. Any documented episode of ATA lasting more than 30 s was considered as a recurrent arrhythmic event. All targeted veins were isolated (100%). Phrenic nerve palsy with recovery during follow-up occurred in six patients (4.5%), no patient experienced tamponade or a cerebrovascular event. During 12.6 ± 5.4 months of follow-up, 89/133 (67%) patients were free of ATA recurrences. Multivariable analysis revealed recurrence in the blanking period (HR 11.46, 0.95 CI 3.92-33.49, p < 0.001), presence of cardiomyopathy (HR 2.75, 0.95 CI 1.09-6.96, p = 0.032) and PV abnormality (HR 3.56, 0.95 CI 1.21-10.43, p = 0.021) as predictors for late recurrence. CONCLUSION: In patients with persistent AF, second-generation cryoballoon use is associated with an excellent safety profile and favorable outcomes. Arrhythmia recurrence during the blanking period, presence of cardiomyopathy and PV abnormality were independent predictors of long-term AF recurrence.

Connexin45 is expressed in vascular smooth muscle but its function remains elusive.

Connexins (Cx) form gap junctions and allow the coordination of cellular behaviour. In vessels, expression of Cx40, Cx37, and Cx43 is well established and specifically Cx40 serves important functions in endothelial cells. In contrast, expression and physiological functions of Cx45 is unclear although its expression has been suggested in vascular smooth muscle (VSM). Therefore, we studied expression and function of Cx45 in vessels using different mice models allowing to identify and delete Cx45. Smooth muscle cell (SMC)-specific deletion was achieved by the Cre/loxP system using Cre-recombinase driven by a Nestin promoter. Deletion of Cx45 leads concomitantly to the expression of enhanced green fluorescence protein (EGFP) in these mice. Conduction of vasomotor responses was studied in cremasteric arterioles using intravital microscopy and arterial pressure was measured telemetrically. Cx45 is transcriptionally expressed in VSM as detected by EGFP expression in SMC-specific Cx45-deficient mice (Cx45fl/fl:Nestin-Cre) but not in endothelial cells (Cx45fl/fl:TIE2-Cre). Moreover, EGFP was located at VSM cell borders in arterioles of transgenic mice carrying an EGFP-tagged Cx45. Expectedly, arteriolar conduction of dilations evoked by the endothelium-dependent agonist acetylcholine were not different between Cx45fl/fl:Nestin-Cre mice and controls carrying homozygously a floxed Cx45 gene (Cx45fl/fl). Surprisingly, the amplitude of locally initiated endothelium-independent constrictions (K(+)) and dilations (adenosine) declined similarly with distance in both genotypes indicating an intact VSM conduction pathway also in mice being deficient for Cx45 in VSM. Arterial pressure was not different between freely moving Cx45fl/fl and Cx45fl/fl:Nestin-Cre mice during day or night. We conclude that Cx45 is physiologically expressed in VSM, but not in EC in murine arterioles. However, Cx45 is dispensable for the conduction of vasomotor responses along these arterioles. Possibly, other Cx functionally replace the lack of Cx45 in VSM. The reported role of Cx45 in renin secretion does not seem to alter arterial pressure in freely moving mice.