Outcomes of COVID-19 in Patients With a History of Cancer and Comorbid Cardiovascular Disease.

BACKGROUND: Cancer and cardiovascular disease (CVD) are independently associated with adverse outcomes in patients with COVID-19. However, outcomes in patients with COVID-19 with both cancer and comorbid CVD are unknown. METHODS: This retrospective study included 2,476 patients who tested positive for SARS-CoV-2 at 4 Massachusetts hospitals between March 11 and May 21, 2020. Patients were stratified by a history of either cancer (n=195) or CVD (n=414) and subsequently by the presence of both cancer and CVD (n=82). We compared outcomes between patients with and without cancer and patients with both cancer and CVD compared with patients with either condition alone. The primary endpoint was COVID-19-associated severe disease, defined as a composite of the need for mechanical ventilation, shock, or death. Secondary endpoints included death, shock, need for mechanical ventilation, need for supplemental oxygen, arrhythmia, venous thromboembolism, encephalopathy, abnormal troponin level, and length of stay. RESULTS: Multivariable analysis identified cancer as an independent predictor of COVID-19-associated severe disease among all infected patients. Patients with cancer were more likely to develop COVID-19-associated severe disease than were those without cancer (hazard ratio [HR], 2.02; 95% CI, 1.53-2.68; P<.001). Furthermore, patients with both cancer and CVD had a higher likelihood of COVID-19-associated severe disease compared with those with either cancer (HR, 1.86; 95% CI, 1.11-3.10; P=.02) or CVD (HR, 1.79; 95% CI, 1.21-2.66; P=.004) alone. Patients died more frequently if they had both cancer and CVD compared with either cancer (35% vs 17%; P=.004) or CVD (35% vs 21%; P=.009) alone. Arrhythmias and encephalopathy were also more frequent in patients with both cancer and CVD compared with those with cancer alone. CONCLUSIONS: Patients with a history of both cancer and CVD are at significantly higher risk of experiencing COVID-19-associated adverse outcomes. Aggressive public health measures are needed to mitigate the risks of COVID-19 infection in this vulnerable patient population.

First spot urine sodium after initial diuretic identifies patients at high risk for adverse outcome after heart failure hospitalization.

BACKGROUND: Relief of congestion is the primary goal of initial therapy for acute decompensated heart failure (ADHF). Early measurement of urine sodium concentration (UNa) may be useful to identify patients with diminished response to diuretics. The aim of this study was to determine if the first spot UNa after diuretic initiation could select patients likely to require more intensive therapy during hospitalization. METHODS: At the time of admission, 103 patients with ADHF were identified prospectively, and UNa was measured after the first dose of intravenous diuretic. Clinical outcomes were compared for patients with UNa >60 mmol/L and UNa of ≤60 mmol/L, with the primary outcome of a composite of death at 90 days, mechanical circulatory support during admission, and requirement of inotropic support at discharge. RESULTS: Patients with UNa ≤60 had lower admission blood pressure, had less chronic neurohormonal antagonist prior to admission, and were more than twice as likely to experience the primary end point (hazard ratio 2.40, 95% CI 1.02-5.66, P = .045), which was marginally significant after adjusting for renal function and baseline home loop diuretic. Worsening renal function was significantly more common in patients with UNa <60 (23.6% vs 6.5%, P = .05). Although the initial assessment of congestion was similar at admission, patients with low early UNa had a longer length of stay (11 vs 6 days, P < .006) than patients with UNa >60. CONCLUSIONS: Assessment of spot UNa after initial intravenous loop diuretic administration may facilitate identification and triage of a population of HF patients at increased risk for adverse events and prolonged hospitalization.

Visually guided TEE probe insertion, making a case based on anatomic variation: A cadaveric study.

AIMS: The variations in upper esophageal anatomy currently are unknown. This study was carried out to evaluate this variation and assess its impact on transesophageal echocardiography probe insertion. METHODS: We included 9 consecutive cadavers studied at the University of Maryland School of Medicine's Clinical Surgical Laboratory. Each cadaver was first intubated blindly by an echocardiographer (KAA) and then under direct vision with a UE Medical VL 400 video laryngoscope (Newton, MA) by an anesthesiologist (JD). RESULTS: The visually guided method took a shorter average time (19.4 ± 13.4 seconds) and fewer passes (2.4 ± 2.1 passes) than blind insertion (30.3 ± 19.1 seconds, 5.3 ± 3.3 passes). None of the cadavers had the esophagus located directly posterior to the trachea. The esophageal hiatus was posterior and to the right of the trachea in most (n = 6); in these, the traditional "forward" jaw thrust helped to open the esophageal hiatus. Two cadavers had the esophagus and trachea located almost side by side, and in these the "forward" jaw thrust method failed. Instead, the jaw needed to be pulled to the left in order to advance the probe. CONCLUSION: This is the first study to describe anatomic variations in the location of and relationship between the upper esophageal sphincter and the larynx for the purpose of transesophageal echocardiography probe insertion. Awareness of the side-by-side anatomic variation can help to improve esophageal intubation by prompting the use of a new "pull to the side" technique instead of the traditional "forward" jaw thrust.

Identifying patients for safe early hospital discharge following st elevation myocardial infarction.

OBJECTIVES: To examine whether the CADILLAC risk score is an effective method of patient stratification for early discharge following ST elevation myocardial infarction (STEMI). BACKGROUND: Patients with STEMI are typically hospitalized to monitor for serious complications such as arrhythmias, heart failure, and reinfarction. Optimal length of stay is unclear. Whether low risk patients can be safely discharged before 72 hr of hospitalization is unclear. METHODS: Patients with STEMI who underwent successful PCI were retrospectively stratified using CADILLAC risk score to low risk (n = 123) and intermediate to high risk (n = 105). The primary outcome was adverse clinical events at day 3 or later. Secondary outcomes were adverse clinical events on day 1 and mortality rates at 30 days and 31 to 365 days. RESULTS: Low risk patients had lower major adverse clinical events at day 3 or later (0 vs. 11.4%, P = 0.0002) and lower total mortality at 1 year (0 vs. 4.8%, P = 0.02) than patients with intermediate to high risk. Low risk patients were also less likely to have a cardiovascular event during the first 24 hr when compared to those with an intermediate to high risk score (3.3% vs. 13.3%, P = 0.006). CONCLUSION: Low risk patients identified using CADILLAC risk score with STEMI treated successfully with primary PCI have a low adverse event rate on the third day or later of hospitalization suggesting that an earlier discharge is safe in properly selected patients. Monitoring in a noncritical care setting following primary PCI for STEMI may be feasible for selected patients. © 2016 Wiley Periodicals, Inc.

Intracranial hemorrhage as a complication of dobutamine stress echocardiography: case report and review of the literature.

Dobutamine stress echocardiography is a generally well-tolerated study to evaluate patients with suspected coronary artery disease. Rare but life-threatening complications of this study have been well described. Severe hypertensive responses are a known but uncommon adverse reaction to dobutamine infusion. The authors report a case of intracranial hemorrhage in the setting of severe hypertension as a complication of dobutamine stress echocardiography. The patient was on systemic anticoagulation with warfarin for a prosthetic mitral valve and had an international normalized ratio (INR) of 3.8 that was slightly over the therapeutic goal INR of 2.5-3.5. He had no predisposing intracranial lesions such as tumor, vascular malformation, or aneurysm. He suffered an intraparenchymal hemorrhage in three distinct areas of his brain. Intracranial hemorrhage related to dobutamine infusion has not been reported previously, but given the known risk of hypertension, life-threatening sequelae including intracranial hemorrhage are possible.

Does loss of spondylolisthesis reduction impact clinical and radiographic outcomes after minimally invasive transforaminal lumbar interbody fusion?

BACKGROUND CONTEXT: Minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) is a common operative approach to address degenerative lumbar stenosis and spondylolisthesis which has failed nonoperative care. Compared to open TLIF, MI-TLIF relies to a greater extent on indirect decompression resulting in a heightened awareness of spondylolisthesis reduction among MI surgeons. To what extent intraoperative reduction is achieved as well as the rate and clinical impact of loss or reduction and slip recurrence remain unknown. PURPOSE: To determine the rate and clinical impact of slip recurrence after MI-TLIF with expandable cage technology STUDY DESIGN/SETTING: Retrospective Cohort Study PATIENT SAMPLE: Patients undergoing MI-TLIF for degenerative spondylolisthesis using an articulating, expandable cage OUTCOME MEASURES: Patient-reported outcome measures (PROMs), including the Oswestry Disability Index (ODI), visual analog scale (VAS) for back/leg pain, Short Form-12 (SF-12), and PROMIS Physical Function (PF) METHODS: Patients undergoing MI-TLIF for degenerative spondylolisthesis using articulating, expandable cages from 2017 to 2019 were retrospectively studied. Lateral radiographs were reviewed and evaluated for the presence or absence of spondylolisthesis preoperatively, intraoperatively, and at follow-up times including 2 weeks, 6 weeks, 12 weeks, 6 months, and 1 year postoperatively. Spondylolisthesis was measured from the posterior inferior corner of the cephalad vertebra to the posterior superior corner of the caudal vertebra, with any measurement >1 mm classified as spondylolisthesis, and Meyerding grade was noted. Intraoperative reduction was measured, and loss of reduction was defined as >1 mm increase in spondylolisthesis comparing follow-up imaging to intraoperative films. PROMs were recorded at the preoperative and follow-up time points. Fusion was assessed at 1 year postoperatively via CT. RESULTS: A total of 63 patients and 70 levels were included, with mean age 59.8 years (SD,13.8). 19 levels (27.1%) had complete reduction intraoperatively, 40 (57.1%) had partial reduction, and 11 (15.7%) had no reduction. Of the 30 levels with loss of reduction (50.8%), 20 (66.7%) occurred by 2 weeks postoperatively and 28 (93.3%) occurred by 12 weeks postoperatively. At 6 months, there were significant differences between those who had loss of reduction and those who did not in VAS back pain (3.0 vs. 0.9, p = .017) and SF-12 PCS (41.5 vs. 50.0, p = .035), but no differences were found between the groups for any instruments at any other time points. The overall fusion rate was 82.1% (32/39) at 1 year postoperatively. There was no significant difference in fusion rate between the loss of reduction (16/20) and no loss of reduction (20/23) groups. Patients with loss of reduction had no difference in reoperation rate (1/28) compared to those without loss of reduction (2/24). CONCLUSIONS: While a majority of patients demonstrated reduction intraoperatively, 51% had loss of reduction, most commonly in the acute postoperative period. There were few differences in PROMs between patients who had loss of reduction and those who did not, suggesting that radiographic loss of reduction after MI-TLIF in the setting of degenerative spondylolisthesis may not be clinically meaningful.

Implantable devices for heart failure monitoring.

Heart failure (HF) is associated with considerable morbidity and mortality. The increasing prevalence of HF and inpatient HF hospitalization has a considerable burden on healthcare cost and utilization. The recognition that hemodynamic changes in pulmonary artery pressure (PAP) and left atrial pressure precede the signs and symptoms of HF has led to interest in hemodynamic guided HF therapy as an approach to allow earlier intervention during a heart failure decompensation. Remote patient monitoring (RPM) utilizing telecommunication, cardiac implantable electronic device parameters and implantable hemodynamic monitors (IHM) have largely failed to demonstrate favorable outcomes in multicenter trials. However, one positive randomized clinical trial testing the CardioMEMS device (followed by Food and Drug Administration approval) has generated renewed interest in PAP monitoring in the HF population to decrease hospitalization and improve quality of life. The COVID-19 pandemic has also stirred a resurgence in the utilization of telehealth to which RPM using IHM may be complementary. The cost effectiveness of these monitors continues to be a matter of debate. Future iterations of devices aim to be smaller, less burdensome for the patient, less dependent on patient compliance, and less cumbersome for health care providers with the integration of artificial intelligence coupled with sophisticated data management and interpretation tools. Currently, use of IHM may be considered in advanced heart failure patients with the support of structured programs.

Electrocardiogram Criteria to Diagnose Cardiac Amyloidosis in Men With a Bundle Branch Block.

Diagnosing cardiac amyloidosis is challenging and requires a high index of suspicion in patients with an increased left ventricular wall thickness (LVWT). Low QRS voltage on electrocardiogram (ECG) has been regarded as the hallmark ECG finding in cardiac amyloidosis; however, the presence of low voltage can range from 20-74% and the voltage/mass ratio carries a greater diagnostic accuracy than QRS voltage alone. Patients with cardiac amyloidosis can have conduction system infiltration and this may result in a BBB. Therefore, the ECG or mass/voltage criteria established for patients with a narrow QRS in the diagnosis of cardiac amyloidosis may not be applicable in patients with a BBB. We sought to identify criteria to aid in the diagnosis of cardiac amyloidosis in patients with increased LVWT on echocardiogram and with a BBB on ECG. We calculated the total QRS score/LVWT, limb lead QRS score/LVWT, R in lead aVL/LVWT, R in lead I/LVWT, and Sokolow index/LVWT. In patients with an increase in LVWT and BBB, total QRS voltage that is indexed to wall thickness can help distinguish between patients with increased wall thickness who have cardiac amyloidosis from those who have LVH related to a pressure overload state. A unique index of Total QRS Score/LVWT is the best predictor of cardiac amyloidosis with a cutoff value of 92.5 mV/cm which is 100% sensitive and 83% specific for the diagnosis of cardiac amyloidosis. This may be a useful screening tool in patients with an increased wall thickness to raise diagnostic suspicion for cardiac amyloidosis.

Angiotensin II Administration in Patients With COVID-19 Shock.

PURPOSE: To understand the hemodynamic effect of angiotensin II as a vasopressor in patients with shock secondary to COVID-19 infection. METHODS: A retrospective analysis was performed on all patients at a single center with COVID-19 infection and shock who were treated with angiotensin II. The hemodynamic response to angiotensin II was estimated by recording the mean arterial pressure, norepinephrine equivalent dose (NED) and urine output. RESULTS: Ten patients with COVID-19 related shock were treated with angiotensin II. Over the initial 6 hours, the average the NED decreased by 30.4% (from 64.6 to 44 µg/min) without a significant change in the mean arterial pressure (0.7% decrease). Six patients experienced at least a 25% reduction in NED by 6 hours, and 2 experienced at least a 50% reduction. CONCLUSIONS: On average, the hemodynamic response to angiotensin II in COVID-19 related shock was favorable. Two patients had a marked rapid improvement. Given the relationship of SARS-CoV-2 with the renin-angiotensin-aldosterone system, further evaluation of angiotensin II for the treatment of COVID-19 related shock is warranted.

Impella CP Implantation during Cardiopulmonary Resuscitation for Cardiac Arrest: A Multicenter Experience.

BACKGROUND: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown. METHODS: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival. RESULTS: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min (p = 0.035 and p = 0.008, respectively). CONCLUSIONS: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.

Power versus manual pedicle tract preparation: a multi-center study of early adopters.

STUDY DESIGN: Retrospective cohort, multicenter. A single surgeon study demonstrated that pedicle tract preparation with power tools was associated with lower fluoroscopy times and revision rates compared to manual tools, while maintaining patient safety. OBJECTIVE: Our purpose was to determine the safety of power-assisted pedicle tract preparation by early adopters of this technology. METHODS: Retrospective review comparing patients that underwent posterior spinal fusion by seven pediatric spine surgeons at six institutions between January 1, 2008 and August 31, 2019. The manual pedicle tract preparation used a pedicle awl. Power tract preparation used a flexible 2.0-2.4 mm drill bit, followed by a larger drill bit or a reamer. All screws were inserted with power technique. RESULTS: In the manual tract preparation group, 9424 screws were placed in 585 cases. In the power tract preparation group, 22,209 screws were placed in 1367 cases. Seven patients (7/1952; 0.36%; 95% CI: 0.14-0.74%) had 11 mal-positioned screws (11/31,633; 0.03%; 95% CI: 0.017-0.062%). Seven screws (7/9424; 0.07%; 95% CI: 0.030-0.15%) were in the manual cohort and four (4/22,209; 0.02%; 95% CI: 0.0049-0.046%) were in the power cohort. There were significantly more revisions per screw in the manual cohort (p = 0.02). However, there were not significantly more revisions per patient in the manual cohort (manual: 0.5%, 3/585 vs. power: 0.3%, 4/1,367; p = 0.43). Of these seven, three patients (3/585; 0.5%; 95% CI: 0.1-1.5%) experienced neurologic injury or neuro-monitoring changes requiring screw removal in the manual cohort, and 1 patient (1/1,367, 0.07%; 95% CI: 0.002-0.4%) in the power cohort (p = 0.08). Three additional patients underwent revision in the power cohort: 1 for an asymptomatic lateral breech, 1 for a spinal headache/medial breech that developed after an MVA, and 1 for an iliac vein injury during pedicle tract preparation. CONCLUSION: This is the first multi-center study examining power pedicle preparation. Overall, 99.9% of pedicle screws placed with power pedicle preparation did not have complications or revision. Equivalent patient safety was demonstrated compared to manual technique. LEVEL OF EVIDENCE: III.

Management of Patients With Giant Cell Myocarditis: JACC Review Topic of the Week.

Giant cell myocarditis is a rare, often rapidly progressive and potentially fatal, disease due to T-cell lymphocyte-mediated inflammation of the myocardium that typically affects young and middle-aged adults. Frequently, the disease course is marked by acute heart failure, cardiogenic shock, intractable ventricular arrhythmias, and/or heart block. Diagnosis is often difficult due to its varied clinical presentation and overlap with other cardiovascular conditions. Although cardiac biomarkers and multimodality imaging are often used as initial diagnostic tests, endomyocardial biopsy is required for definitive diagnosis. Combination immunosuppressive therapy, along with guideline-directed medical therapy, has led to a paradigm shift in the management of giant cell myocarditis resulting in an improvement in overall and transplant-free survival. Early diagnosis and prompt management can decrease the risk of transplantation or death, which remain common in patients who present with cardiogenic shock.

Cardiotoxicity of Contemporary Anticancer Immunotherapy.

PURPOSE OF REVIEW: Contemporary anticancer immunotherapy, particularly immune checkpoint inhibitors (ICI) and chimeric antigen receptor (CAR) T cell therapy, has changed the landscape of treatment for patients with a variety of malignancies who historically had a poor prognosis. However, both immune checkpoint inhibitors and CAR T cell therapy are associated with serious cardiovascular adverse effects. As immunotherapy evolves to include high-risk patients with preexisting cardiovascular risk factors and disease, the risk and relevance of its associated cardiotoxicity will be even higher. RECENT FINDINGS: ICI can cause myocarditis, which usually occurs early after initiation, can be fulminant, and prompt treatment with high-dose corticosteroids is crucial. CAR T cell therapy frequently leads to cytokine release syndrome, which is associated with cardiomyopathy or arrhythmia development and may also result in circulatory collapse. Supportive treatment, as well as tocilizumab, an anti-interleukin-6 receptor antibody, is the cornerstone of treatment. Recent findings suggest that preexisting cardiovascular risk factors and disease may increase the risk of such cardiotoxicity, and prompt recognition, as well as treatment, may favorably alter the outcomes. SUMMARY: ICI and CAR T cell therapy have improved cancer-related outcomes; however, they both are associated with potentially therapy-limiting cardiotoxicity. Cardio-oncologists are required to play an important role in patient selection, pretherapy cardiovascular optimization, and prompt recognition and treatment of cardiotoxicity.

Risk and predictors of dyssynchrony cardiomyopathy in left bundle branch block with preserved left ventricular ejection fraction.

BACKGROUND: Left bundle branch block (LBBB) and left ventricular (LV) dyssynchrony likely contribute to progressive systolic dysfunction. The evaluation of newly recognized LBBB includes screening for structural heart abnormalities and coronary artery disease (CAD). In patients whose LV ejection fraction (EF) is preserved during initial testing, the incidence of subsequent cardiomyopathy is not firmly established. HYPOTHESIS: The risk of developing LV systolic dysfunction among LBBB patients with preserved LVEF is high enough to warrant serial imaging. METHODS: We screened records of 1000 consecutive patients with LBBB from our ECG database and identified subjects with an initially preserved LVEF (≥45%) without clinically relevant CAD or other cause for cardiomyopathy. Baseline imaging, clinical data, and follow-up imaging were recorded to determine the risk of subsequent LV systolic dysfunction (LVEF ≤40%). RESULTS: (Data are mean + SD) 784 subjects were excluded, the majority for CAD or depressed LVEF upon initial imaging. Of the remaining 216, 37 (17%) developed a decline in LVEF(≤40%) over a mean follow-up of 55 ± 31 months; 94% of these patients had a baseline LVEF≤60% and LV end systolic diameter (ESD) ≥ 2.9 cm indicating that these measures may be useful to define which patients warrant longitudinal follow-up. The negative predictive value of a LVEF>60% and LVESD <2.9 cm was 98%. CONCLUSIONS: Seventeen percent of patients with LBBB and initial preserved LVEF develop dyssynchrony cardiomyopathy. We believe the risk of developing dyssynchrony cardiomyopathy is high enough to warrant serial assessment of LV systolic function in this high-risk population.

Outcomes of Impella CP insertion during cardiac arrest: A single center experience.

OBJECTIVES: We sought to determine the outcomes of patients with an Impella CP percutaneous mechanical circulatory support (MCS) device deployed during a cardiac arrest. BACKGROUND: The Impella CP device is indicated for left ventricular support in patients with cardiogenic shock. The utility of percutaneous MCS in the setting of cardiac arrest during cardiopulmonary resuscitation (CPR) remains unclear. METHODS: We retrospectively examined data from patients supported with an Impella CP device for cardiogenic shock complicated by cardiac arrest between April 2015 and April 2017 at a single academic medical center. Patients with cardiac arrest who underwent Impella CP placement during CPR were compared to those who had return of spontaneous circulation (ROSC) prior to Impella CP placement. RESULTS: We identified 22 patients with cardiogenic shock complicated by cardiac arrest (average age 64 years, 23% female) who underwent placement of an Impella CP device. The majority of patients (68%) underwent support for cardiogenic shock secondary to an acute myocardial infarction. Seven of the 22 patients (32%) underwent Impella CP placement during CPR and 15 (68%) underwent Impella CP insertion following ROSC. The in-hospital mortality was 86% in the group of patients who had the Impella CP placed during CPR and 56% in the group with ROSC prior to Impella CP insertion, (p = 0.19). CONCLUSIONS: Based on our single center retrospective analysis, the mortality rate of patients undergoing placement of an Impella CP during CPR is 86%. Further study is necessary to better understand the utility of the Impella CP mechanical circulatory support device during a cardiac arrest.

Global Longitudinal Strain and Cardiac Events in Patients With Immune Checkpoint Inhibitor-Related Myocarditis.

BACKGROUND: There is a need for improved methods for detection and risk stratification of myocarditis associated with immune checkpoint inhibitors (ICIs). Global longitudinal strain (GLS) is a sensitive marker of cardiac toxicity among patients receiving standard chemotherapy. There are no data on the use of GLS in ICI myocarditis. OBJECTIVES: This study sought to evaluate the role of GLS and assess its association with cardiac events among patients with ICI myocarditis. METHODS: This study retrospectively compared echocardiographic GLS by speckle tracking at presentation with ICI myocarditis (cases, n = 101) to that from patients receiving an ICI who did not develop myocarditis (control subjects, n = 92). Where available, GLS was also measured pre-ICI in both groups. Major adverse cardiac events (MACE) were defined as a composite of cardiogenic shock, arrest, complete heart block, and cardiac death. RESULTS: Cases and control subjects were similar in age, sex, and cancer type. At presentation with myocarditis, 61 cases (60%) had a normal ejection fraction (EF). Pre-ICI, GLS was similar between cases and control subjects (20.3 ± 2.6% vs. 20.6 ± 2.0%; p = 0.60). There was no change in GLS among control subjects on an ICI without myocarditis (pre-ICI vs. on ICI, 20.6 ± 2.0% vs. 20.5 ± 1.9%; p = 0.41); in contrast, among cases, GLS decreased to 14.1 ± 2.8% (p < 0.001). The GLS at presentation with myocarditis was lower among cases presenting with either a reduced (12.3 ± 2.7%) or preserved EF (15.3 ± 2.0%; p < 0.001). Over a median follow-up of 162 days, 51 (51%) experienced MACE. The risk of MACE was higher with a lower GLS among patients with either a reduced or preserved EF. After adjustment for EF, each percent reduction in GLS was associated with a 1.5-fold increase in MACE among patients with a reduced EF (hazard ratio: 1.5; 95% confidence interval: 1.2 to 1.8) and a 4.4-fold increase with a preserved EF (hazard ratio: 4.4; 95% confidence interval: 2.4 to 7.8). CONCLUSIONS: GLS decreases with ICI myocarditis and, compared with control subjects, was lower among cases presenting with either a preserved or reduced EF. Lower GLS was strongly associated with MACE in ICI myocarditis presenting with either a preserved or reduced EF.

Influenza vaccination and myocarditis among patients receiving immune checkpoint inhibitors.

BACKGROUND: Influenza vaccination (FV) is recommended for patients with cancer. Recent data suggested that the administration of the FV was associated with an increase in immune-related adverse events (irAEs) among patients on immune checkpoint inhibitors (ICIs). Myocarditis is an uncommon but serious complication of ICIs and may also result from infection with influenza. There are no data testing the relationship between FV and the development of myocarditis on ICIs. METHODS: Patients on ICIs who developed myocarditis (n = 101) (cases) were compared to ICI-treated patients (n = 201) without myocarditis (controls). A patient was defined as having the FV if they were administered the FV from 6 months prior to start of ICI to anytime during ICI therapy. Alternate thresholds for FV status were also tested. The primary comparison of interest was the rate of FV between cases and controls. Patients with myocarditis were followed for major adverse cardiac events (MACE), defined as the composite of cardiogenic shock, cardiac arrest, hemodynamically significant complete heart block and cardiovascular death. RESULTS: The FV was administered to 25% of the myocarditis cases compared to 40% of the non-myocarditis ICI-treated controls (p = 0.01). Similar findings of lower rates of FV administration were noted among myocarditis cases when alternate thresholds were tested. Among the myocarditis cases, those who were vaccinated had 3-fold lower troponin levels when compared to unvaccinated cases (FV vs. No FV: 0.12 [0.02, 0.47] vs. 0.40 [0.11, 1.26] ng/ml, p = 0.02). Within myocarditis cases, those administered the FV also had a lower rate of other irAEs when compared to unvaccinated cases (36 vs. 55% p = 0.10) including lower rates of pneumonitis (12 vs. 36%, p = 0.03). During follow-up (175 [IQR 89, 363] days), 47% of myocarditis cases experienced a MACE. Myocarditis cases who received the FV were at a lower risk of cumulative MACE when compared to unvaccinated cases (24 vs. 59%, p = 0.002). CONCLUSION: The rate of FV among ICI-related myocarditis cases was lower than controls on ICIs who did not develop myocarditis. In those who developed myocarditis related to an ICI, there was less myocardial injury and a lower risk of MACE among those who were administered the FV.

Myocarditis in Patients Treated With Immune Checkpoint Inhibitors.

BACKGROUND: Myocarditis is an uncommon, but potentially fatal, toxicity of immune checkpoint inhibitors (ICI). Myocarditis after ICI has not been well characterized. OBJECTIVES: The authors sought to understand the presentation and clinical course of ICI-associated myocarditis. METHODS: After observation of sporadic ICI-associated myocarditis cases, the authors created a multicenter registry with 8 sites. From November 2013 to July 2017, there were 35 patients with ICI-associated myocarditis, who were compared to a random sample of 105 ICI-treated patients without myocarditis. Covariates of interest were extracted from medical records including the occurrence of major adverse cardiac events (MACE), defined as the composite of cardiovascular death, cardiogenic shock, cardiac arrest, and hemodynamically significant complete heart block. RESULTS: The prevalence of myocarditis was 1.14% with a median time of onset of 34 days after starting ICI (interquartile range: 21 to 75 days). Cases were 65 ± 13 years of age, 29% were female, and 54% had no other immune-related side effects. Relative to controls, combination ICI (34% vs. 2%; p < 0.001) and diabetes (34% vs. 13%; p = 0.01) were more common in cases. Over 102 days (interquartile range: 62 to 214 days) of median follow-up, 16 (46%) developed MACE; 38% of MACE occurred with normal ejection fraction. There was a 4-fold increased risk of MACE with troponin T of ≥1.5 ng/ml (hazard ratio: 4.0; 95% confidence interval: 1.5 to 10.9; p = 0.003). Steroids were administered in 89%, and lower steroids doses were associated with higher residual troponin and higher MACE rates. CONCLUSIONS: Myocarditis after ICI therapy may be more common than appreciated, occurs early after starting treatment, has a malignant course, and responds to higher steroid doses.