Prognostic Implication of Pre-Cannulation Cardiac Arrest in Patients Undergoing Extracorporeal Membrane Oxygenation for the Management of Cardiogenic Shock.

BACKGROUND: The application of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) in contemporary management of cardiogenic shock (CS) has dramatically increased. Despite increased utilization, few predictive models exist to estimate patient survival based on pre-ECMO characteristics. Furthermore, the prognostic implications of pre-ECMO cardiac arrest are not well defined. METHODS: Utilizing an institutional VA-ECMO database, all consecutive patients undergoing VA-ECMO for the management of CS from January 1, 2014, to July 1, 2019, were identified. Survival to hospital discharge was analyzed based on cannulation indication in patients with and without pre-ECMO cardiac arrest. Patients who received extracorporeal cardiopulmonary resuscitation (eCPR) were analyzed separately. RESULTS: Of the 214 patients identified, 110 did not suffer a cardiac arrest prior to cannulation (cohort 1), 57 patients had a cardiac arrest with sustained ROSC (cohort 2), and 47 were cannulated as a component of eCPR (cohort 3). Despite sustained ROSC (cohort 2), the presence of pre-ECMO cardiac arrest was associated with a significant reduction in survival to hospital discharge (22.8% vs. 55.5% in cohort 1; p < 0.001). Comparatively, survival to discharge was similar in patients undergoing eCPR (22.8% vs. 17.0%; p = 0.464). Finally, patients with a cardiac arrest were significantly more likely to have a neurological etiology death with VA-ECMO than patients supported prior to hemodynamic collapse (18.3% vs. 2.7%; p < 0.001). This result is seen in those with sustained ROSC (21.1% vs. 2.7%; p < 0.001) and those with eCPR (14.9% vs. 2.7%; p = 0.004). CONCLUSION: In our cohort, pre-ECMO cardiac arrest carries a negative prognostic value across all indications and is associated with an increased prevalence of neurological-etiology death. This finding is true in patients with sustained ROSC as well as those resuscitated with eCPR. Cardiac arrest can inform survival probability with VA-ECMO as early implementation of VA-ECMO may mitigate adverse outcomes in patients at the highest risk of hemodynamic collapse.

Establishing a Cardiac ICU Recovery Clinic: Characterizing a Model for Continuity of Cardiac Critical Care.

BACKGROUND: Care in the cardiovascular intensive care unit (CICU) has become increasingly intricate due to a temporal rise in noncardiac diagnoses and overall clinical complexity with high risk for short-term rehospitalization and mortality. Survivors of critical illness are often faced with debility and limitations extending beyond the index hospitalization. Comprehensive ICU recovery programs have demonstrated some efficacy but have primarily targeted survivors of acute respiratory distress syndrome or sepsis. The efficacy of dedicated ICU recovery programs on the CICU population is not defined. METHODS: We aim to describe the design and initial experience of a novel CICU-recovery clinic (CICURC). The primary outcome was death or rehospitalization in the first 30 days following hospital discharge. Self-reported outcome measures were performed to assess symptom burden and independence in activities of daily living. RESULTS: Using standardized criteria, 41 patients were referred to CICURC of which 78.1% established care and were followed for a median of 88 (56-122) days. On intake, patients reported a high burden of heart failure symptoms (KCCQ overall summary score 29.8 [18.0-47.5]), and nearly half (46.4%) were dependent on caretakers for activities of daily living. Thirty days postdischarge, no deaths were observed and the rate of rehospitalization for any cause was 12.2%. CONCLUSIONS: CICU survivors are faced with significant residual symptom burden, dependence upon caretakers, and impairments in mental health. Dedicated CICURCs may help prioritize treatment of ICU related illness, reduce symptom burden, and improve outcomes. Interventions delivered in ICU recovery clinic for patients surviving the CICU warrant further investigation.

Predicting mortality in nonsurgical patients before cannulation for veno-arterial extracorporeal life support: Development and validation of the LACT-8 score.

OBJECTIVES: We sought to derive and validate a model to predict inpatient mortality after veno-arterial extracorporeal life support (VA-ECLS) based on readily available, precannulation clinical data. BACKGROUND: Refractory cardiogenic shock supported by VA-ECLS is associated with high morbidity and mortality. METHODS: VA-ECLS cases at our institution from January 2014 through July 2019 were retrospectively reviewed. Exclusion criteria were cannulation: (1) at another institution; (2) for primary surgical indication; or (3) for extracorporeal cardiopulmonary resuscitation. Multivariable logistic regression compared those with and without inpatient mortality. Multiple imputation was performed and optimism-adjusted area under the curve (oAUC) values were computed. RESULTS: VA-ECLS cases from August 2019 through November 2020 were identified as a validation cohort. In the derivation cohort (n = 135), the final model included Lactate (mmol/L), hemoglobin (g/dl; Anemia), Coma (Glasgow Coma Scale [GCS] < 8) and resusciTATEd cardiac arrest (LACTATE score; oAUC = 0.760). In the validation cohort (n = 30, LACTATE showed similar predictability [AUC = 0.710]). A simplified (LACT-8) score was derived by dichotomizing lactate (>8) and hemoglobin (<8) and summing together the number of components for each patient. LACT-8 performed similarly (derivation, oAUC = 0.724; validation, AUC = 0.725). In the derivation cohort, both scores outperformed SAVE (oAUC = 0.568) and SOFA (oAUC = 0.699) scores. A LACT-8 ≥ 3 had a specificity for mortality of 97.9% and 92.9%, in the derivation and validation cohorts, respectively. CONCLUSIONS: The LACT-8 score can predict inpatient mortality prior to before cannulation for VA-ECLS. LACT-8 can be implemented utilizing clinical data without the need for an online calculator.

Characteristics of diabetes medication-taking in people with mild to moderate intellectual disability compared to those without: a mixed-methods study.

AIM: To compare the frequency and factors associated with diabetes medication-taking (depression, perceived side effects, self-efficacy and social support) in people with mild to moderate intellectual disability and those without intellectual disability. METHODS: In stage 1 of this study, we collated information on diabetes medication-taking and associated factors in 111 people with diabetes: 33 adults with mild to moderate intellectual disability and 78 adults without intellectual disability. Validated instruments measuring medicine-taking, self efficacy, depressive symptoms, perceived level of social support and perceived side effects were administered in both groups. In stage 2, we used an abductive qualitative approach to triangulate stage 1 findings with carers responses (n = 12). RESULTS: The instruments showed good internal reliability (Cronbach's α = 0.7-0.9). Comparisons between people with intellectual disabilities and those without revealed similar frequency of medication-taking (70% vs 62%; P = 0.41). People with intellectual disabilities and diabetes had significantly higher depressive symptoms, as measured by the Glasgow Depression Scale for people with a Learning Disability (P = 0.04), higher levels of perceived side effects (P = 0.01), and lower confidence levels, as measured by the Perceived Confidence Scale (P = 0.01). The results of stage 2 showed how carers of people with intellectual disabilities and diabetes optimized medication-taking yet infrequently discussed the side effects of medicines. CONCLUSIONS: Further investigation of medication-taking and side effects may result in the development of an evidence-informed intervention to improve medicines safety in people with intellectual disabilities.

Reduction of radiation and contrast agent exposure in a cryoballoon ablation procedure with integration of electromagnetic mapping and intracardiac echocardiography: a single center experience.

BACKGROUND: Pulmonary vein isolation (PVI) with cryoballoon ablation (CBA) is routinely guided by fluoroscopy and utilizes contrast injection to ensure catheter positioning and pulmonary vein occlusion. Non-fluoroscopic imaging techniques including electromagnetic mapping (EM) and intracardiac echocardiography (ICE) have demonstrated reduced fluoroscopy times and contrast exposure. Utilization of color flow Doppler to evaluate vein occlusion with the balloon has not been evaluated as an alternative to contrast injection. In this study we evaluate the effectiveness of cryoablation guided by EM and ICE along with color Doppler to achieve PVI. METHODS: We designed a retrospective cohort study comparing patients who were treated before and after implementation of EM (Carto 3, Biosense Webster) and ICE during CBA (AF Solutions, Medtronic). We analyzed patients receiving CBA with fluoroscopy plus EM and ICE (group 2; N = 24) versus fluoroscopy alone (group 1; N = 25). Procedural success was defined as freedom from atrial fibrillation or other atrial arrhythmias at 1 year post ablation. Primary outcomes were radiation time and contrast exposure. RESULTS: Procedural success was achieved in all cases. Total fluoroscopy time was reduced from 22.4 ± 9.8 min to 8.9 ± 5.1 min (P < 0.001) in patients receiving CBA guided by EM and ICE. Furthermore, exposure to contrast media was significantly lower at 75.4 ± 24.1 ml and 16.5 ± 21.1 ml (P ≤ 0.001) in group 1 and group 2, respectively. Neither the number of required cryotherapy treatments nor procedure duration was negatively impacted by the implementation of non-fluoroscopic techniques. The 1-year success rate was identical between both groups at 72% and 79%. There was no difference in complication rates. CONCLUSION: This single-center cohort study demonstrates that CBA guided by EM and ICE can markedly reduce radiation and contrast exposure with excellent rates of acute PVI. This technique may be particularly effective in patients sensitive to intravenous contrast exposure.

Stentablation with Rotational Atherectomy for the Management of Underexpanded and Undilatable Coronary Stents.

Stentablation with rotational atherectomy for the management of undilatable underexpanded coronary stents is a unique application associated with excellent periprocedural and in-hospital outcomes. Data regarding long-term outcomes remains limited, however the procedure appears to be associated with high prevalence of target lesion revascularization. Given the complexity of such lesions and few available interventional remedies; it is a reasonably safe and widely available approach of which operators should be aware. When stentablation is performed, the principles which guide contemporary rotational atherectomy and percutaneous coronary intervention, including intravascular imaging, should be applied.

Prevalence and clinical characteristics associated with left atrial thrombus detection: Apixaban.

BACKGROUND: The prevalence of left atrial appendage (LAA) thrombus detection by transesophageal echocardiogram (TEE) in patients with non-valvular atrial fibrillation (AF) anticoagulated with apixaban is not well defined and identification of additional risk factors may help guide the selection process for pre-procedural TEE. The purpose of our study was to retrospectively analyze the prevalence of LAA thrombus detection by TEE in patients continuously anticoagulated with apixaban for ≥ 4 wk and evaluate for any cardiac risk factors or echocardiographic characteristics which may serve as predictors of thrombus formation. AIM: To retrospectively analyze the prevalence of LAA thrombus detection by TEE in patients continuously anticoagulated with apixaban. METHODS: Clinical and echocardiographic data for 820 consecutive patients with AF undergoing TEE at Augusta University Medical Center over a four-year period were retrospectively analyzed. All patients (apixaban: 226) with non-valvular AF and documented compliance with apixaban for ≥ 4 wk prior to index TEE were included. RESULTS: Following ≥ 4 wk of continuous anticoagulation with apixaban, the prevalence of LAA thrombus and LAA thrombus/dense spontaneous echocardiographic contrast was 3.1% and 6.6%, respectively. Persistent AF, left ventricular ejection fraction < 30%, severe LA dilation, and reduced LAA velocity were associated with thrombus formation. Following multivariate logistic regression, persistent AF (OR: 7.427; 95%CI: 1.02 to 53.92; P = 0.0474), and reduced LAA velocity (OR: 1.086; 95%CI: 1.010 to 1.187; P = 0.0489) were identified as independent predictors of LAA thrombus. No Thrombi were detected in patients with a CHA2DS2-VASc score ≤ 1. CONCLUSION: Among patients with non-valvular AF and ≥ 4 wk of anticoagulation with apixaban, the prevalence of LAA thrombus detected by TEE was 3.1%. This suggests that continuous therapy with apixaban does not completely eliminate the risk of LAA thrombus and that TEE prior to cardioversion or catheter ablation may be of benefit in patients with multiple risk factors.

Safety and Efficacy of Stentablation with Rotational Atherectomy for the Management of Underexpanded and Undilatable Coronary Stents.

INTRODUCTION: Coronary stent underexpansion is associated with in-stent restenosis and few interventions are available for the management of undilatable underexpanded stents. Stentablation (SA) with rotational atherectomy (RA) is a unique application and has previously been described with encouraging results. Data regarding SA is limited to case reports and small case series; therefore, reasonable concern persists regarding procedural safety and long-term outcomes. METHODS: This is a single-center retrospective study analyzing twenty consecutive patients who underwent SA with RA. The primary endpoint was procedural success and secondary endpoints included procedural safety outcomes and major adverse cardiac events (MACE) over a 12-month follow-up period. RESULTS: Stentablation and secondary stenting were guided by intravascular ultrasound and procedural success was achieved in all cases. No in-hospital death or MACE was observed. The prevalence of MACE was 5% at 30 days as one patient developed recurrent MI without target lesion revascularization (TLR). At 12 months, MACE had occurred in 40% of patients, however this was strongly driven by a high prevalence of TLR (30%). Only one cardiac death (5%) and one additional NSTEMI were observed during the 11 additional months of follow up. CONCLUSION: Stentablation with RA is a feasible and effective option for the acute management of symptomatic, underexpanded, and undilatable coronary stents. SA is associated with a high rate of procedural success as well as excellent in-hospital and short-term outcomes. However, our study population demonstrated substantial MACE at 12 months which was strongly driven by TLR and associated with minimal mortality.

Outcomes of rotational atherectomy in patients with severe left ventricular dysfunction without hemodynamic support.

INTRODUCTION: Elective insertion of a percutaneous circulatory assist device (PCAD) in high-risk patients is considered a reasonable adjunct to percutaneous coronary intervention (PCI). There is limited data examining the safety and efficacy of rotational atherectomy (RA) without hemodynamic support in patients with reduced left ventricular ejection fraction (LVEF). METHODS: We retrospectively identified 131 consecutive patients undergoing RA without elective PCAD over a three-year period. Patients were categorized into three groups: LVEF ≤30%, LVEF 31-50%, and LVEF >50%. The incidence of procedural hypotension, major adverse cardiac events (MACE), and mortality were recorded. RESULTS: Statistical analysis included 18, 42, and 71 patients with LVEF ≤30%, 31-50%, and >50%, respectively. Bailout hemodynamic support was required in four cases. Analysis revealed a significant trend as bailout hemodynamic support was required in 11.1% vs 2.4% (P = 0.1551) in the ≤30% vs 31-50% and 11.1% vs 1.4% (P = 0.0416) in the ≤30% vs >50% subgroups. Combined subgroup analysis also demonstrated statistical significance 11.1% vs 1.8% (P = 0.0324) in the ≤30% vs >30% subgroups. No-reflow phenomenon was more prevalent in patients with reduced LVEF (LVEF ≤30%: 11.1%, LVEF 31-50%: 2.4%, LVEF >50%: 0%; P = 0.0190). Otherwise, no significant differences in in-hospital MACE, or mortality were observed. CONCLUSION: RA can be effectively utilized in patients with severely reduced LVEF; however, these patients are at increased risk of prolonged procedural hypotension requiring bailout hemodynamic support. If indicated, prompt implementation of hemodynamic support mitigated any impact of procedural hypotension on in-hospital MACE and mortality.

Efficacy of a heparin based rota-flush solution in patients undergoing rotational atherectomy.

INTRODUCTION: The efficacy of heparin based flush solutions in rotational atherectomy (RA) has not been validated. Recently, a single center study demonstrated the feasibility of an alternative flush solution with 10,000U of unfractionated heparin (UFH) in 1L of normal saline. We aimed to evaluate the safety and efficacy of an alternative flush solution intermittently utilized at our institution. METHODS: We retrospectively identified 150 patients undergoing RA over a three year period. One hundred cases utilized an alternative flush solution containing 10,000U UFH, 400mcg nitroglycerin, and 10mg verapamil in 1L normal saline and fifty cases utilized RotaGlide Lubricant (Boston Scientific) in addition to heparin and vasodilators in the same dose. The primary end point was to compare rates of procedural success. Secondary endpoints were to report procedural characteristics including the incidence of major adverse cardiac events (MACE) and minor periprocedural complications. RESULTS: Procedural success was achieved in 98% (98/100) of cases utilizing the alternative Rota-Flush solution compared to 100% (50/50) in the Rota-Glide group (P=0.553). A total of 292 lesions (200 Rota-Flush vs 92 Rota-Glide) were targeted for intervention. MACE occurred in 13 (13%) and 4 (8%) cases in the Rota-Flush and Rota-Glide groups, respectively (P=0.425). CONCLUSION: Rotational atherectomy performed with the previously defined Rota-Flush or Rota-Glide solutions resulted in similar rates of procedural success. There were no significant disparities in incidence of MACE and minor periprocedural complications between the two groups. Heparin based rota-flush solutions can be effective alternatives to traditional solutions containing RotaGlide Lubricant.

A refined linkage map for DNA markers around the pericentromeric region of chromosome 10.

A refined genetic linkage map for the pericentromeric region of human chromosome 10 has been constructed from data on 12 distinct polymorphic DNA loci as well as the locus for multiple endocrine neoplasia type 2A (MEN 2A), a dominantly inherited cancer syndrome. The map extends from D10S24 (at 10p13-p12.2) to D10S3 (at 10q21-q23) and is about 70 cM long. Overall, higher female than male recombination frequencies were observed for this region, with the most remarkable female excess in the immediate vicinity of the centromere, as previously reported. Most of the DNA markers in this map are highly informative for linkage and the majority of the interlocus intervals are no more than 6 cM apart. Thus this map should provide a fine framework for future efforts in more detailed mapping studies around the centromeric area. A set of ordered cross-overs identified in this work is a valuable resource for rapidly and accurately localizing new DNA clones isolated from the pericentromeric region.

The genetic defect in multiple endocrine neoplasia type 2A maps next to the centromere of chromosome 10.

Multiple endocrine neoplasia type 2A (MEN2A) is a rare cancer syndrome that is inherited in an apparently autosomal dominant fashion. Previous linkage studies had assigned the MEN2A locus to chromosome 10 in the pericentromeric region. We recently have described several new easily scorable RFLPs for the chromosome 10-specific alpha satellite DNA (the D10Z1) locus that is known, on the basis of previous in situ hybridization experiments, to lie at the centromere. We report here tight linkage between MEN2A and D10Z1, as demonstrated by a maximum lod score of 12.02 at the recombination frequency of zero (1-lod-unit support interval 0-4 cM), indicating that the genetic defect in MEN2A lies in the immediate vicinity of the centromere. By means of a set of ordered polymorphic DNA markers from the pericentromeric region, multipoint as well as pairwise linkage analyses place the MEN2A locus at the middle of a small region (approximately 11 cM) bracketing the centromere with FNRB (at 10p11.2) and RBP3 (at 10q11.2) on either side, providing further support for the centromeric location of the MEN2A locus. Marked sex difference in recombination frequencies exists in this pericentromeric region: significantly (P less than .01) more female than male crossovers were observed across all of the adjacent intervals D10S24-FNRB, FNRB-D10Z1, and D10Z1-RBP3. However, a sex difference was not seen in the 7-cM interval from RBP3 to D10S5, suggesting that large variation in the sex difference in recombination can occur over small chromosomal regions.(ABSTRACT TRUNCATED AT 250 WORDS)

The beta subunit locus of the human fibronectin receptor: DNA restriction fragment length polymorphism and linkage mapping studies.

The beta subunit of the human fibronectin receptor (FNRB) is a transmembrane protein belonging to the VLA (very late antigens of activation) family. Using pGEM-32, a 2.5-kb partial cDNA clone corresponding to the 3' portion of the human FNRB locus, multiple restriction fragment length polymorphisms (RFLPs) were revealed on DNAs from unrelated Caucasians. RFLPs detected by five enzymes, BanII, HinfI, KpnI, BglII, and SacI, are of the simple two-allele form, and pairwise linkage analyses of these RFLPs with numerous known DNA markers from the chromosome-10 pericentromeric region not only confirmed the chromosome-10 assignment of the functional FNRB gene but also supported its localization at p11.2 suggested by in situ hybridization. An infrequent MspI RFLP was detected by pB/R2, a 4.6-kb genomic clone from the FNRB locus. Another type of DNA polymorphism was also revealed by the cDNA clone and it was visualized on the Southern blot analyses as the presence or absence of an extra band (or a set of extra bands). It seems to stem from a stretch of DNA sequence present in some individuals at one single locus but absent in others, and is of non-chromosome-10 origin based on linkage analyses with known chromosome 10 markers. This "presence/absence" type of polymorphism could be revealed by all of the 25 restriction enzymes tested and is similar in nature to that previously reported with one of the human dihydrofolate reductase pseudogenes, DHFRP1. Dissection of the pGEM-32 clone demonstrated that the region revealing the non-chromosome-10 sequences is within a fragment about 1.7 kb in length extending from about 600 nucleotides preceding the stop codon down to the end of the cloned FNRB 3' untranslated region. Due to its high polymorphism information content (PIC) value (0.71 for haplotypes of BanII, HinfI, and KpnI RFLPs) and proximity to the centromere. FNRB will prove to be a highly useful marker for genetic linkage studies of multiple endocrine neoplasia type 2A (MEN2A) as well as for chromosome-10 linkage studies in general.

The nature of the toxic reaction of influenza virus towards lung tissue.

The inoculation of large doses of unadapted influenza virus intranasally into mice results in the production of severe lung lesions. This toxic effect is a result of the entry of virus particles into the lung cells followed by uncoating of the virus ribonucleic acid.The toxic property of the virus is destroyed by procedures which destroy or modify the nucleic acid such as exposure to monochromatic UV light of wavelength 2537 A, or treatment with hydroxylamine or Bayer A139. Reagents acting on amino groups are particularly effective as they react with the nucleic acid and probably also interfere with penetration of virus into the cell.Toxicity is also destroyed by mercurials which probably prevent uncoating of the nucleic acid by union with disulphide bonds, and by oxidizing agents such as iodine, permanganate, osmic acid and hydrogen peroxide under condition which suggest possible action on some constituent of the virus containing methionine.The toxic effect produced by the inoculation of large doses of unadapted virus intranasally in mice is associated with the occurrence of an incomplete growth cycle in which there is full production of RNP antigen but no production of haemagglutinin or infective virus.

The chemical reactions of the haemagglutinins and neuraminidases of different strains of influenza viruses. 3. Effects of proteolytic enzymes.

The action of trypsin and pronase on the haemagglutinins and neuraminidases of eight strains of influenza virus has been examined.The haemagglutinins of all the strains were highly susceptible to digestion by pronase but there were great variations in resistance to trypsin.The neuraminidases of the eight strains were of three types. The neuraminidases of the A 1 strains and the DSP strain of virus A were highly susceptible to destruction by both enzymes. The neuraminidases of the PR 8 and Swine strains showed partial resistance especially to trypsin, while the A 2 strains and the LEE strains of virus B possessed neuraminidases that were completely resistant to both trypsin and pronase.Proteolytic enzymes released free neuraminidases from the A 2 and LEE viruses the morphology of which was different from that of neuraminidases released by detergent treatment.