Biomechanical Impact of Pathogenic MYBPC3 Truncation Variant Revealed by Dynamically Tuning In Vitro Afterload.

Engineered cardiac microtissues were fabricated using pluripotent stem cells with a hypertrophic cardiomyopathy associated c. 2827 C>T; p.R943x truncation variant in myosin binding protein C (MYBPC3+/-). Microtissues were mounted on iron-incorporated cantilevers, allowing manipulations of cantilever stiffness using magnets, enabling examination of how in vitro afterload affects contractility. MYPBC3+/- microtissues developed augmented force, work, and power when cultured with increased in vitro afterload when compared with isogenic controls in which the MYBPC3 mutation had been corrected (MYPBC3+/+(ed)), but weaker contractility when cultured with lower in vitro afterload. After initial tissue maturation, MYPBC3+/- CMTs exhibited increased force, work, and power in response to both acute and sustained increases of in vitro afterload. Together, these studies demonstrate that extrinsic biomechanical challenges potentiate genetically-driven intrinsic increases in contractility that may contribute to clinical disease progression in patients with HCM due to hypercontractile MYBPC3 variants.

Anatomical/Physiological Correlates of Functional Capacity in Adults With Repaired and Nonsevere Coarctation of the Aorta.

Background: There is limited data regarding the interplay of anatomic and physiologic parameters with exercise capacity in adults with native or recurrent nonsevere coarctation of the aorta (CoA). Objectives: The objective of this study was to use exercise stress echocardiography and cardiac magnetic resonance imaging to identify anatomic and physiologic correlates of exercise capacity in these patients. Methods: We conducted a single-center retrospective analysis of 54 adults with nonsevere CoA (repaired or unrepaired) followed at our institution between 2015 and 2020. Resting coarctation gradients were obtained using echocardiography. Exercise gradients and functional capacity were assessed using exercise stress echocardiography. Aorta anatomy was obtained using magnetic resonance imaging. Results: Coarctation-to-diaphragm ratio correlated with minutes of exercise (r = 0.56, P < 0.01) and metabolic equivalents (r = 0.49, P < 0.01). These relationships remained significant after controlling for use of beta-blockers, valvular disease, and type of coarctation repair. Minutes of exercise correlated with mean resting gradients (r = -0.39, P < 0.05). Coarctation-to-diaphragm ratio correlated with peak and mean resting gradients (r = -0.34, P < 0.05; r = -0.48, P < 0.01). Patients with coarctation-to-diaphragm ratio ≤0.7 achieved fewer metabolic equivalents (11.1 ± 1.9 vs 12.8 ± 2.2, P < 0.05) and minutes of exercise (10.3 ± 2.0 vs 12.6 ± 2.7, P < 0.05). Conclusions: In patients with nonsevere native or recurrent CoA, reduced exercise capacity is correlated with coarctation severity by anatomic size and gradients. Those with a coarctation-to-diaphragm ratio ≤0.7 may represent a subset of patients with nonsevere CoA whose clinical symptoms are only elicited with exercise stress testing. Exercise stress testing and cross-sectional imaging may help identify those who could be considered for earlier coarctation intervention.

Outcomes After Tricuspid Valve Operations in Patients With Drug-Use Infective Endocarditis.

The increase of intravenous drug use has led to an increase in right-sided infective endocarditis and its complications including septic pulmonary embolism. The objective of this study was to compare the outcomes of tricuspid valve (TV) operations in patients with drug-use infective endocarditis (DU-IE) complicated by septic pulmonary emboli (PE). Hospitalizations for DU-IE complicated by septic PE were identified from the National Inpatient Sample from 2002 to 2019. Outcomes of patients who underwent TV operations were compared with medical management. The primary outcome was the incidence of major adverse cardiovascular events (MACEs), defined as in-hospital mortality, myocardial infarction, stroke, cardiogenic shock, or cardiac arrest. An inverse probability of treatment weighted analysis was utilized to adjust for the differences between the cohorts. A total of 9,029 cases of DU-IE with septic PE were identified (mean age 33.6 years), of which 818 patients (9.1%) underwent TV operation. Surgery was associated with a higher rate of MACE (14.5% vs 10.8%, p <0.01), driven by a higher rate of cardiogenic shock (6.1% vs 1.2%, p <0.01) but a lower rate of mortality (2.7% vs 5.7%, p <0.01). Moreover, TV operation was associated with an increased need for permanent pacemakers, blood transfusions, and a higher risk of acute kidney injury. In the inverse probability treatment weighting analysis, TV operation was associated with an increased risk for MACE driven by a higher rate of cardiogenic shock and cardiac arrest, but a lower rate of mortality when compared with medical therapy alone. In conclusion, TV operations in patients with DU-IE complicated by septic PE are associated with an increased risk for MACE but a decreased risk of mortality. Although surgical management may be beneficial in some patients, alternative options such as percutaneous debulking should be considered given the higher risk.

Long-term follow-up of acute and chronic rejection in heart transplant recipients from hepatitis C viremic (NAT+) donors.

The long-term safety of heart transplants from hepatitis C viremic (NAT+) donors remains uncertain. We conducted a prospective study of all patients who underwent heart transplantation at our center from January 2018 through August 2020. Routine testing was performed to assess for donor-derived cell-free DNA, acute cellular rejection (ACR), antibody-mediated rejection (AMR), and cardiac allograft vasculopathy (CAV). Allograft dysfunction and mortality were also monitored. Seventy-five NAT- recipients and 32 NAT+ recipients were enrolled in the study. All NAT+ recipients developed viremia detected by PCR, were treated with glecaprevir/pibrentasvir at the time of viremia detection, and cleared the virus by 59 days post-transplant. Patients who underwent NAT testing starting on post-operative day 7 (NAT+ Group 1) had significantly higher viral loads and were viremic for a longer period compared with patients tested on post-operative day 1 (NAT+ Group 2). Through 3.5 years of follow-up, there were no statistically significant differences in timing, severity, or frequency of ACR in NAT+ recipients compared with the NAT- cohort, nor were there differences in noninvasive measures of graft injury, incidence or severity of CAV, graft dysfunction, or mortality. There were five episodes of AMR, all in the NAT- group. There were no statistically significant differences between Group 1 and Group 2 NAT+ cohorts. Overall, these findings underscore the safety of heart transplantation from NAT+ donors.

Invasive Management of Acute Myocardial Infarctions During the Initial Wave of the COVID-19 Pandemic.

BACKGROUND: The initial wave of the coronavirus disease 2019 (COVID-19) pandemic resulted in an influx of patients with acute viral illness and profound changes in healthcare delivery in New York City. The impact of this pandemic on the presentation and invasive management of acute myocardial infarction (MI) is not well described. METHODS: This single-center retrospective study compared patients with MI who underwent invasive coronary angiography at New York University from March-April 2020, during the peak of the first wave of the pandemic, with those presenting in March-April 2019. RESULTS: Only 35 patients with MI underwent angiography during the study period in 2020 vs 109 patients in 2019. No differences in comorbidities or baseline medications were identified. The proportion of patients with ST-segment elevation MI (STEMI) was higher in 2020 than in 2019 (48.6% vs 24.8%, respectively; P=.01). Median peak troponin concentration was higher (14.5 ng/mL vs 2.9 ng/mL; P<.01) and left ventricular ejection fraction was lower (43.34% vs 51.1%; P=.02) during the pandemic. Among patients with non-STEMI, time from symptom onset to presentation was delayed in 2020 compared with 2019 (median, 24 hours vs 10 hours; P=.04). CONCLUSION: There was a dramatic decrease in the number of patients with MI undergoing coronary angiography during the first wave of the COVID-19 pandemic. Of those who presented, patients tended to seek care later after symptom onset and had excess myocardial injury. These data indicate a need for improved patient education to ensure timely cardiovascular care during public health emergencies.

Short-Segment Type B Interrupted Aortic Arch Presenting With Subarachnoid Hemorrhage With Subsequent Primary Percutaneous Repair.

This report describes a young adult man presenting with subarachnoid hemorrhage secondary to an intracranial aneurysm who was found to have a short-segment type B interrupted aortic arch. We describe the clinical presentation, evaluation, and management of this patient and highlight imaging findings and percutaneous repair of the aneurysm and interrupted aortic arch. (Level of Difficulty: Intermediate.).

Acquired pulmonary vein stenosis resulting in haemoptysis: a case series.

BACKGROUND: Acquired pulmonary vein stenosis (PVS) is an infrequent complication of atrial fibrillation ablation that is often misdiagnosed due to predominant respiratory symptoms. It can result in pulmonary venous hypertension, with varying presentations, ranging from shortness of breath to haemoptysis. CASE SUMMARY: We report two patients with a history of paroxysmal atrial fibrillation treated with radiofrequency ablation and pulmonary vein (PV) isolation, who subsequently developed PVS. Case 1 initially presented with indolent symptoms of shortness of breath and cough. He was initially diagnosed with and treated for pneumonia. In contrast, Case 2 presented with massive haemoptysis, requiring intubation and intensive care unit admission. Both patients were eventually diagnosed with PVS by computed tomography. They were treated with PV angioplasty and stenting. DISCUSSION: While previously limited to the congenital heart disease population, PVS is occurring more frequently now in adult patients as a complication of ablation procedures. It is most effectively treated with angioplasty and stent implantation but has a high rate of recurrence.

Comparison of outcomes of pulmonary valve replacement in adult versus paediatric hospitals: institutional influence†.

OBJECTIVES: Controversy exists in ascertaining the ideal location for adults with congenital heart disease requiring surgical intervention. In this study, we sought to compare the perioperative management between our paediatric and adult hospitals and to determine how clinical factors and the location affect the length of stay after pulmonary valve replacement. METHODS: A retrospective analysis of patients, ≥18 years of age, undergoing pulmonary valve replacement was conducted at our paediatric and adult hospitals between 1 January 2000 and 30 October 2014. Patients with previous Ross or concomitant left heart procedures were excluded. Descriptive statistics were used to assess demographics and clinical characteristics. Inverse probability weight-adjusted models were used to determine differences in the number of surgical complications, duration of mechanical ventilation and postoperative length of stay between paediatric and adult hospitals. Additional models were calculated to identify factors associated with prolonged length of stay. RESULTS: There were altogether 98 patients in the adult (48 patients) and paediatric (50 patients) hospitals. Patients in the adult hospital were older with more comorbidities (arrhythmia, hypertension, depression and a history of cardiac arrest, all P < 0.05). Those at the paediatric hospital had better preoperative right ventricular function and less tricuspid regurgitation. The cardiopulmonary bypass time, the length of intubation and the length of stay were higher at the adult hospital, despite no difference in the number of complications between locations. Factors contributing to the increased length of stay include patient characteristics and postoperative management strategies. There were no deaths. CONCLUSIONS: Pulmonary valve replacement may be performed safely with no deaths and with a comparable complication rate at both hospitals. Patients undergoing surgery at the adult hospital have longer intubation times and length of stay. Opportunities exist to streamline management strategies.

Quantifying [¹8F]fluorodeoxyglucose uptake in the arterial wall: the effects of dual time-point imaging and partial volume effect correction.

PURPOSE: The human arterial wall is smaller than the spatial resolution of current positron emission tomographs. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake. We evaluated the impact of a novel method for partial volume effect (PVE) correction with contrast-enhanced CT (CECT) assistance on quantification of arterial wall (18)F-FDG uptake at different imaging time-points. METHODS: Ten subjects were assessed by CECT imaging and dual time-point PET/CT imaging at approximately 60 and 180 min after (18)F-FDG administration. For both time-points, uptake of (18)F-FDG was determined in the aortic wall by calculating the blood pool-corrected maximum standardized uptake value (cSUVMAX) and cSUVMEAN. The PVE-corrected SUVMEAN (pvcSUVMEAN) was also calculated using (18)F-FDG PET/CT and CECT images. Finally, corresponding target-to-background ratios (TBR) were calculated. RESULTS: At 60 min, pvcSUVMEAN was on average 3.1 times greater than cSUVMAX (P < .0001) and 8.5 times greater than cSUVMEAN (P < .0001). At 180 min, pvcSUVMEAN was on average 2.6 times greater than cSUVMAX (P < .0001) and 6.6 times greater than cSUVMEAN (P < .0001). CONCLUSION: This study demonstrated that CECT-assisted PVE correction significantly influences quantification of arterial wall (18)F-FDG uptake. Therefore, partial volume effects should be considered when quantifying arterial wall (18)F-FDG uptake with PET.