Severe hypocalcaemia mimicking acute coronary syndrome.

Hypocalcaemia is a common electrolyte deficiency that can be found in up to 28% of hospitalised patients. It may affect cardiac and smooth muscle tone, leading to ECG abnormalities and, in rare cases, coronary spasms and heart failure. This is a case of a pregnant woman in preterm labour who developed vasospastic angina and corrected QT interval (QTc) prolongation on ECG from severe hypocalcaemia, which likely occurred due to iatrogenic hypermagnesaemia. She had a negative diagnostic workup for acute coronary syndrome, and her chest pain and QTc prolongation ultimately resolved with intravenous electrolyte repletion. This case highlights the importance of considering hypocalcaemia on the differential of chest pain that is possibly cardiac in origin.

Hypertension, smoking, and preexistence of multiple cardiac risk factors correlate with carfilzomib-induced cardiovascular adverse events in a racially diverse population.

Background: Use of the proteasome inhibitor carfilzomib has become a standard of care in patients with relapsed/refractory multiple myeloma. An association between carfilzomib and cardiovascular adverse events has been well documented, but this had not been investigated in a racially diverse population. Black patients in particular are underrepresented in the reported outcomes of treatment with carfilzomib. Objective: The purpose of this study was to identify risk factors for carfilzomib-associated cardiovascular events in a diverse, single-center population. Methods: We conducted a retrospective review of 161 patients with multiple myeloma treated with carfilzomib between 2011 and 2020 at the University of Maryland Medical Center. Over half (86) were Black patients, with the remainder (75) being White patients. We did a multivariate analysis to determine risk factors for developing cardiovascular events during treatment with carfilzomib. Results: There was no statistically significant association with cardiotoxicity and race, gender, or age at first dose of carfilzomib. In multivariable analysis, patients with history of hypertension had a higher risk of cardiotoxicity [adjusted odds ratio (OR): 2.5; 95% CI: 1.1-5.9; P = 0.03] as did those with a history of smoking [OR: 2.8; 95% CI: 1.3-6.4; P = 0.01]. Conclusions: Here we report the largest cohort of Black patients treated with carfilzomib as yet reported. The results of this single center retrospective study show history of hypertension and smoking are associated with carfilzomib associated cardiotoxicity in a diverse patient population. There is a need for well-designed prospective studies enrolling a diverse population to investigate potential interventions to prevent carfilzomib-associated cardiotoxicity.

Development of a Reproducible Swine Model of Chronic Ischemic Mitral Regurgitation: Lessons Learned.

BACKGROUND: Durability of mitral valve repair for ischemic mitral regurgitation (IMR) remains poor. We established a swine model of chronic IMR, and describe the methods and lessons learned from this model. METHODS: Thirty-five swine underwent percutaneous myocardial infarction with ethanol ablation of the circumflex or obtuse marginal (OM) arteries. Swine were followed with routine echocardiography for the development of severe IMR. Once severe IMR was established, swine underwent mitral valve operations on cardiopulmonary bypass. After operation, swine were survived up to 7 weeks. Angiographic and echocardiographic features of swine who developed severe IMR (IMR swine) and those who did not (non-IMR swine) were compared. RESULTS: The median number of OM arteries was 3, with 2 OM arteries infarcted. Acute survival after the myocardial infarction was 74% (26 of 35) with 3 (9%) early, postoperative deaths. Among the 23 swine with follow-up to determine IMR status, 14 of 23 (61%) developed significant IMR. Among IMR pigs, left ventricular (LV) ejection fraction decreased from 65% pre-myocardial infarction to 45% pre-mitral valve intervention (P < .001). Among non-IMR swine, LV ejection fraction decreased nonsignificantly from baseline (60%) to latest follow-up (55%) (P = .443). LV end-diastolic dimension (P = .039), wall motion score (P = .027), global circumferential strain (P = .014), and global longitudinal strain (P = .023) were significantly worse in IMR compared with non-IMR swine. CONCLUSIONS: A reproducible percutaneous model of severe IMR in swine is feasible with a guided anesthetic and perioperative approach. This model can serve as a platform to better understand the mechanism of IMR and subsequently to test novel repair techniques.

The ABO histo-blood group, endothelial activation, and acute respiratory distress syndrome risk in critical illness.

BACKGROUNDThe ABO histo-blood group is defined by carbohydrate modifications and is associated with risk for multiple diseases, including acute respiratory distress syndrome (ARDS). We hypothesized that genetically determined blood subtype A1 is associated with increased risk of ARDS and markers of microvascular dysfunction and coagulation.METHODSWe conducted analyses in 3 cohorts of critically ill trauma and sepsis patients (n = 3710) genotyped on genome-wide platforms to determine the association of the A1 blood type genotype with ARDS risk. We subsequently determined whether associations were present in FUT2-defined nonsecretors who lack ABO antigens on epithelium, but not endothelium. In a patient subgroup, we determined the associations of blood type with plasma levels of endothelial glycoproteins and disseminated intravascular coagulation (DIC). Lastly, we tested whether blood type A was associated with less donor lung injury recovery during human ex vivo lung perfusion (EVLP).RESULTSThe A1 genotype was associated with a higher risk of moderate to severe ARDS relative to type O in all 3 populations. In sepsis, this relationship was strongest in nonpulmonary infections. The association persisted in nonsecretors, suggesting a vascular mechanism. The A1 genotype was also associated with higher DIC risk as well as concentrations of thrombomodulin and von Willebrand factor, which in turn were associated with ARDS risk. Blood type A was also associated with less lung injury recovery during EVLP.CONCLUSIONWe identified a replicable association between ABO blood type A1 and risk of ARDS among the critically ill, possibly mediated through microvascular dysfunction and coagulation.FUNDINGNIH HL122075, HL125723, HL137006, HL137915, DK097307, HL115354, HL101779, and the University of Pennsylvania McCabe Fund Fellowship Award.

Degenerative Mitral Valve Repair Simplified: An Evolution to Universal Artificial Cordal Repair.

BACKGROUND: Resectional and artificial cordal repair techniques are effective strategies for degenerative mitral valve (MV) repair. However, resectional repair requires a tailored approach using various techniques, whereas cordal repair offers a simpler, easily reproducible repair. The approach described in this study approach has evolved from resectional to cordal over time, and outcomes are compared between the eras. METHODS: Clinical and echocardiographic outcomes of all patients undergoing MV repair for degenerative mitral regurgitation (MR) from January 2004 to September 2017 were reviewed. Patients were stratified by era: from January 2004 to June 2011 (era 1; n = 405), resectional techniques were used in 62% and artificial cordal techniques were used in 38%. From July 2011 to September 2017 (era 2; n = 438), artificial cordal repair was used in 98% of patients. The primary outcome was repair failure, defined as greater than moderate MR or MV reoperation. RESULTS: Of 847 patients with degenerative MR, successful repair was achieved in 843 patients (99.5% repair rate). Leaflet prolapse was posterior in 66%, anterior in 8%, and bileaflet in 26%. Cardiopulmonary bypass time and cross-clamp times were shorter in era 2 (CPB: 109 [IQR, 92-128] minutes vs 97 [IQR, 76-121] minutes; P < .001; cross-clamp: 88 [IQR, 73-106] minutes vs. 79 [IQR, 61-99] minutes; P < .001). Predismissal echocardiography demonstrated no MR or trace MR in 95%, mild MR in 4.7%, and moderate MR in 0.3% of patients. Operative mortality was similar in the eras (0.5% vs 0.5%; P > .999). The rates of 5-year freedom from repair failure (95.1% vs 95.5%; P = .707), stroke (96.8% vs 95.3%; P = .538), and endocarditis (99.3% vs 99.7%; P = .604) were similar between the eras. CONCLUSIONS: Artificial cordal repair for all patients with degenerative MR simplifies MV repair and yields equivalent, excellent outcomes compared with a tailored resectional approach.

Differences in Hearing Acuity among "Normal-Hearing" Young Adults Modulate the Neural Basis for Speech Comprehension.

In this paper, we investigate how subtle differences in hearing acuity affect the neural systems supporting speech processing in young adults. Auditory sentence comprehension requires perceiving a complex acoustic signal and performing linguistic operations to extract the correct meaning. We used functional MRI to monitor human brain activity while adults aged 18-41 years listened to spoken sentences. The sentences varied in their level of syntactic processing demands, containing either a subject-relative or object-relative center-embedded clause. All participants self-reported normal hearing, confirmed by audiometric testing, with some variation within a clinically normal range. We found that participants showed activity related to sentence processing in a left-lateralized frontotemporal network. Although accuracy was generally high, participants still made some errors, which were associated with increased activity in bilateral cingulo-opercular and frontoparietal attention networks. A whole-brain regression analysis revealed that activity in a right anterior middle frontal gyrus (aMFG) component of the frontoparietal attention network was related to individual differences in hearing acuity, such that listeners with poorer hearing showed greater recruitment of this region when successfully understanding a sentence. The activity in right aMFGs for listeners with poor hearing did not differ as a function of sentence type, suggesting a general mechanism that is independent of linguistic processing demands. Our results suggest that even modest variations in hearing ability impact the systems supporting auditory speech comprehension, and that auditory sentence comprehension entails the coordination of a left perisylvian network that is sensitive to linguistic variation with an executive attention network that responds to acoustic challenge.