Changes in Care for Acute Pulmonary Embolism Through A Multidisciplinary Pulmonary Embolism Response Team.

BACKGROUND: Optimal management of acute pulmonary embolism requires expertise offered by multiple subspecialties. As such, pulmonary embolism response teams (PERTs) have increased in prevalence, but the institutional consequences of a PERT are unclear. METHODS: We compared all patients that presented to our institution with an acute pulmonary embolism in the 3 years prior to and 3 years after the formation of our PERT. The primary outcome was in-hospital pulmonary embolism-related mortality before and after the formation of the PERT. Sub-analyses were performed among patients with elevated-risk pulmonary embolism. RESULTS: Between August 2012 and August 2018, 2042 patients were hospitalized at our institution with acute pulmonary embolism, 884 (41.3%) pre-PERT implementation and 1158 (56.7%) post-PERT implementation, of which 165 (14.2%) were evaluated by the PERT. There was no difference in pulmonary embolism-related mortality between the two time periods (2.6% pre-PERT implementation vs 2.9% post-PERT implementation, P = .89). There was increased risk stratification assessment by measurement of cardiac biomarkers and echocardiograms post-PERT implementation. Overall utilization of advanced therapy was similar between groups (5.4% pre-PERT implementation vs 5.4% post-PERT implementation, P = 1.0), with decreased use of systemic thrombolysis (3.8% pre-PERT implementation vs 2.1% post-PERT implementation, P = 0.02) and increased catheter-directed therapy (1.3% pre-PERT implementation vs 3.3% post-PERT implementation, P = 0.05) post-PERT implementation. Inferior vena cava filter use decreased after PERT implementation (10.7% pre-PERT implementation vs 6.9% post-PERT implementation, P = 0.002). Findings were similar when analyzing elevated-risk patients. CONCLUSION: Pulmonary embolism response teams may increase risk stratification assessment and alter application of advanced therapies, but a mortality benefit was not identified.

Fluoropyrimidine-Associated Cardiotoxicity: A Retrospective Case-Control Study.

BACKGROUND: The fluoropyrimidines, 5-fluorouracil (5-FU) and capecitabine, are commonly used chemotherapeutic agents that have been associated with coronary vasospasm. METHODS: In this retrospective case-control study, we identified patients at our institution who received 5-FU or capecitabine in 2018. We compared characteristics of patients who experienced cardiotoxicity with controls. We described phenotypes and outcomes of cardiotoxic cases. RESULTS: We identified 177 patients who received fluoropyrimidines. After adjudication, 4.5% of the cohort met the criteria for cardiovascular toxicity. Coronary artery disease was more common among cases than controls (38% vs. 7%, p < .05). There was also a trend toward increased prevalence of cardiovascular risk factors in cases compared with controls. Most cardiotoxic cases had chest pain, although a minority of cases presented with nonischemic cardiomyopathy. CONCLUSION: Cardiotoxicity phenotypes associated with fluoropyrimidine use are not limited to coronary vasospasm. Cardiac risk factors and ischemic heart disease were highly prevalent among patients with cardiotoxicity.

Fluoropyrimidine-Associated Cardiotoxicity.

Fluoropyrimidines are chemotherapeutic agents that confer great benefit to many patients with solid tumors, but their use is often limited by cardiotoxicity. The incidence and precise mechanisms of cardiotoxicity remain uncertain. Clinical presentations of fluoropyrimidine toxicity are varied and include chest pain, myocardial infarction, acute cardiomyopathy, arrhythmia, cardiogenic shock, and sudden cardiac death. Proposed mechanisms include coronary vasospasm, coronary endothelial dysfunction, direct myocardial toxicity, myocarditis, and Takotsubo cardiomyopathy. Therapeutic and prophylactic interventions primarily target coronary vasospasm as the underlying cause. Prospective studies are needed to develop evidence-based approaches to cardioprotection in patients receiving fluoropyrimidines.

Vasopressin antagonism for decompensated right-sided heart failure.

BACKGROUND: Targeted treatment for decompensated right heart failure (RHF) with or without left heart failure is lacking. Vasopressin antagonists (vaptans) may offer an option by increasing urine output and fluid mobilization when used in acute decompensated RHF without impacting blood pressure or renal function, both common complications of loop diuretics. METHODS AND RESULTS: We searched electronic medical records from 2 institutions over 4 years for patients with RHF treated with vaptans. Urine output, creatinine, BUN and sodium, 1 day pre- versus 1 day post-vaptan initiation were compared. Baseline (admission) pre-vaptan values for patients with RHF who met inclusion criteria (n = 112) were RAP, median (interquartile range) = 19 (13-24) mmHg; cardiac index, mean ±â€¯standard deviation = 1.8 ±â€¯0.4 L/min/m2; BNP, 1078 (523-1690) pg/ml; creatinine clearance of 51 (39-69) ml/min, BUN, 37 (26-54) mg/dl, and serum [Na+] 132 (126-135) mEq/L. Most patients (n = 103/112) received intravenous inotrope (prior to vaptan, n = 91). Overall length of stay was 27 (16-43) days. Vaptan treatment (90% tolvaptan, 10% conivaptan) was associated with increased 24 h urine output, 1517 (906-2394) vs 2337 (1425-3744) mL, p = 0.005, and [Na+], 127 (124-130) vs 130 (126-135) mEq/L, p = 0.001, without significant change in Cr or BUN. Furosemide IV dose equivalent decreased or remained unchanged in 75% of patients at 24 h and 64% at 72 h compared to the 24 h prior to vaptan use. CONCLUSION: Vaptans were associated with a significant increase in urine output and serum sodium with an apparent reduction or stabilization of furosemide equivalent dosing in the early treatment period in patients with decompensated RHF. Vaptans may offer a management option for patients failing conventional diuretic-based treatment.

Cardioprotection in the Modern Era of Cancer Chemotherapy.

The current arsenal of cancer chemotherapy is broad and rapidly expanding and includes conventional cytotoxic agents and targeted and immune-based therapies. As cancer survival rates have improved, the acute and latent cardiotoxicities of chemotherapy have emerged as important contributors to morbidity and mortality in cancer survivors. All chemotherapeutic agents have the potential for cardiac complications, with manifestations ranging from subclinical left ventricular dysfunction and asymptomatic QT prolongation, to congestive heart failure, myocardial ischemia, myocarditis, arrhythmia, and sudden cardiac death. Efforts are ongoing to identify patients at high risk of cardiac complications and to develop evidence-based approaches to cardioprotection. In this review, we describe antitumor agents commonly associated with cardiotoxicity, with a focus on risk assessment, surveillance strategies, and pharmacologic and nonpharmacologic interventions aimed at preventing and mitigating chemotherapy-induced myocardial dysfunction.

A Case Series of Acute Myocardial Infarction in Left Ventricular Assist Device-Supported Patients.

Acute myocardial infarction (AMI) is an underrecognized phenomenon in patients with continuous-flow left ventricular assist devices (CF-LVAD). Previously, there has been an optimistic expectation of a benign clinical course; however, AMI in LVAD-supported patients can result in profound consequences and management remains controversial. We describe a case series of AMI in four CF-LVAD patients, each with a different presentation, clinical course, treatment, and outcome. The clinical variability and mixed outcomes of these patients highlights the unique challenges in diagnosis and management of AMI in this population, particularly the uncertain role of percutaneous intervention (PCI), and underscores the potentially poor prognosis of this entity. Several key points emerge from this review. First, LVAD-supported patients frequently have underlying abnormalities on the electrocardiogram (ECG) that obscure the diagnosis of AMI. Second, clinicians should have a high degree of suspicion for AMI in the presence of suggestive clinical features, elevated cardiac biomarkers, or new-onset ventricular arrhythmias. Third, the decision to proceed with PCI requires careful evaluation of the risk of hemorrhage, and strong consideration should be given to the use of bleeding avoidance strategies during and after PCI.

Ggamma1, a downstream target for the hmgcr-isoprenoid biosynthetic pathway, is required for releasing the Hedgehog ligand and directing germ cell migration.

The isoprenoid biosynthetic pathway leading from the production of mevalonate by HMGCoA reductase (Hmgcr) to the geranylation of the G protein subunit, Ggamma1, plays an important role in cardiac development in the fly. Hmgcr has also been implicated in the release of the signaling molecule Hedgehog (Hh) from hh expressing cells and in the production of an attractant that directs primordial germ cells to migrate to the somatic gonadal precursor cells (SGPs). The studies reported here indicate that this same hmgcr-->Ggamma1 pathway provides a novel post-translational mechanism for modulating the range and activity of the Hh signal produced by hh expressing cells. We show that, like hmgcr, ggamma1 and quemao (which encodes the enzyme, geranylgeranyl diphosphate synthetase, that produces the substrate for geranylation of Ggamma1) are components of the hh signaling pathway and are required for the efficient release of the Hh ligand from hh expressing cells. We also show that the hmgcr-->Ggamma1 pathway is linked to production of the germ cell attractant by the SGPs through its ability to enhance the potency of the Hh signal. We show that germ cell migration is disrupted by the loss or gain of ggamma1 activity, by trans-heterozygous combinations between ggamma1 and either hmgcr or hh mutations, and by ectopic expression of dominant negative Ggamma1 proteins that cannot be geranylated.