Risk profiles and incidence of cardiovascular events across different cancer types.

BACKGROUND: Cancer survivors are at increased risk for cardiovascular (CV) disease, although additional data are needed to better understand the incidence of CV events across different malignancies. This study sought to characterize the incidence of major adverse CV events [myocardial infarction, stroke, unstable angina (MACE), or heart failure (HF)] across multiple cancer types after cancer diagnosis. PATIENTS AND METHODS: Patients were identified from a USA-based administrative claims database who had index cancer diagnoses of breast, lung, prostate, melanoma, myeloma, kidney, colorectal, leukemia, or lymphoma between 2011 and 2019, with continuous enrollment for ≥12 months before diagnosis. Baseline CV risk factors and incidence rates of CV events post-index were identified for each cancer. Multivariable Cox hazards models assessed the cumulative incidence of MACE, accounting for baseline risk factors. RESULTS: Among 839 934 patients across nine cancer types, CV risk factors were prevalent. The cumulative incidence of MACE was highest in lung cancer and myeloma, and lowest in breast cancer, prostate cancer, and melanoma. MACE cumulative incidence for lung cancer was 26% by 4 years (2.7-fold higher relative to breast cancer). The incidence of stroke was especially pronounced in lung cancer, while HF was highest in myeloma and lung cancer. CONCLUSIONS: CV events were especially increased following certain cancer diagnoses, even after accounting for baseline risk factors. Understanding the variable patient characteristics and associated CV events across different cancers can help target appropriate CV risk factor modification and develop strategies to minimize adverse CV events and improve patient outcomes.

Neuregulin in heart failure : reverse translation from cancer cardiotoxicity to new heart failure therapy.

Trastuzumab is a monoclonal antibody to the ErbB2 (Her2nue) receptor over-expressed in Her2(+) breast cancer. Trastuzumab-related cardiotoxicity has revealed the importance of ErbB2 signaling in the heart. Neuregulin (NRG-1) is an important stress-mediated paracrine growth factor that signals through the family of ErbB receptors to promote cardioprotection (myocyte cell survival, proliferation, differentiation, hypertrophy, and angiogenesis). Animal models with disrupted NRG/ErbB signaling fail to develop normally or result in impaired cardiac function post-natally. Pre-clinical animal studies and early-phase human studies suggest that recombinant NRG-1 holds promise as a new therapy for the treatment of various forms of heart failure. Much work is needed to further understand the exact mechanisms of cardiac repair and to find a safe mode of application for recombinant NRG-1 in heart failure.

Computerized tomographic finding of saddle pulmonary embolism is associated with high mortality in cancer patients.

BACKGROUND: Large pulmonary embolism (PE) is associated with high mortality in cancer patients. Several risk stratification methods have been used in PE setting. While computer-assisted tomography (CT) is now the preferred diagnostic modality for PE, its prognostic value is not well established. METHODS: A retrospective study of patients discharged from our centre between 2000 and 2006 with a PE diagnosis identified 52 patients with thrombus in the main pulmonary artery or the right or left branch. Clinical, echocardiographic and CT data were reviewed; vital status was determined 1 month and 1 year after index event. Patients were divided into saddle (defined as main pulmonary artery thrombus) and non-saddle PE. Multivariate logistic regression was applied to predict vital status, with patient age and CT parameters as predictors. RESULTS: Eighteen out of 52 patients were found to have a saddle PE. No significant difference was found between the group characteristics, although saddle PE patients were more likely to receive thrombolytic therapy (27.8% vs 2.9%, P = 0.02) and have an echocardiogram within 30 days of PE (61.1% vs 29.4%, P = 0.03). Overall mortality at 1 month was 9.6% with no difference between groups. At 1 year, mortality rates in saddle PE were significantly higher (83.3% vs 41.2%, P = 0.004). Presence of saddle PE was associated with an odds ratio of death within 1 year of 7.41 (95% confidence interval: 1.75-31.46, P = 0.007). CONCLUSION: The relatively simple distinction of saddle versus non-saddle PE by CT findings may provide a straightforward method for risk stratification, and remains useful up to 1 year after the index event.

Frequency of late potentials on signal-averaged electrocardiograms during thallium stress testing in coronary artery disease.

Late potentials detected by signal-averaged electrocardiography (SAECG) are an important noninvasive indicator identifying patients with previous myocardial infarction at risk for developing ventricular tachycardia. The role of myocardial ischemia in the development of late potentials is undefined. This study attempts to determine if late potentials on SAECG can be produced during scintigraphically proven ischemia. A signal-averaged electrocardiogram was obtained before and immediately after single-photon emission computed tomography thallium exercise testing in 51 patients. Reversible ischemia was documented in 25 cases with no significant changes in the parameters of SAECG; patients with previous myocardial infarction (n = 10) also had no significant changes from baseline. Multivariate analysis with respect to reversible ischemia and previous myocardial infarction was unrevealing. Patients with late potentials at baseline (n = 10) who developed reversible ischemia (n = 5) had a shorter QRS duration than those with late potentials at baseline and no reversible ischemia. The data indicate that exercise-induced scintigraphically proven ischemia does not alter SAECG even in the presence of previous myocardial infarction. Patients with late potentials at baseline may actually have a shortened QRS duration during reversible ischemia as opposed to the expected lengthening of the QRS.

Reliability of technetium-99m Q12 and thallium-201 myocardial activity measurements after triphenyl tetrazolium chloride myocardial staining by perfusion.

RATIONALE AND OBJECTIVES: Investigations in animal models of severe myocardial ischemia or infarction use triphenyl tetrazolium chloride (TTC) staining to document infarction size histologically and to correlate these data with uptake measurements of radiolabeled tracers. Previously published data suggest that TTC staining itself has an important impact on myocardial tracer activity measurements. The authors hypothesized that TTC staining by perfusion has no significant effect on relative regional myocardial activity measurements of technetium-99m Q12 and thallium-201 in an open-chest canine model. METHODS: Eight dogs underwent left anterior descending artery occlusion for 2 hours with 30 minutes of reperfusion, followed immediately by injection of technetium-99m Q12 (n = 4) or thallium-201. Total myocardial activity was recorded in a dose calibrator, and regional myocardial samples were obtained by Cope needle biopsies from the ischemic and normal zones, both before and after TTC staining. RESULTS: The mean percent activity retention for the whole heart after perfusion staining with TTC was significantly reduced when compared to the preperfusion value for both technetium-99m Q12 and thallium-201. Regional measurements revealed no significant difference between the mean percent retention of technetium-99m Q12 in the ischemic and normal zones. After TTC perfusion, regional mean percent retention of thallium-201 was similar in the ischemic and normal zones. CONCLUSIONS: In a canine model of myocardial ischemia and infarction with reperfusion, TTC staining can be performed by coronary artery perfusion without significantly affecting comparative regional measurements of either technetium-99m Q12 or thallium-201. Whole heart tracer retention is significantly reduced by TTC perfusion staining, but thallium-201 is more affected than technetium-99m Q12.

Native valve infective endocarditis: what is the optimal timing for surgery?

IE remains a dreaded disease masquerading under a myriad of presentations in an evolving epidemiological environment. In our continuing endeavor against this deadly disease, echocardiography has evolved into an indispensable diagnostic tool to define structural complications and guide therapy. Timing of surgical intervention for IE remains a subject of intense debate and depends on the cardiac and systemic complications of the infection, the virulence of the organism, and the responsiveness to medical therapy. A judicious agreement among cardiologist, cardiovascular surgeon, and infectious disease specialist should define whether surgical intervention is warranted and, if so, the optimal timing. Further optimization of guidelines will help in the diagnosis and treatment of endocarditis but will never be a substitute for sound judgment and experience.

Nonpharmacologic treatment of heart failure in the elderly.

Nonpharmacologic therapy is an integral part of the management of elderly patients with heart failure. Reinforcement of dietary sodium restriction and other nutritional concerns are critical features of therapy. Quality standards for the management of patients with heart failure are being developed, and the implementation of these standards is a goal of clinicians. A multidisciplinary approach to elderly patients with heart failure is beneficial.

Ticlopidine-induced neutropenia mimicking sepsis early after intracoronary stent placement.

We report a case of ticlopidine-induced profound neutropenia early in the course of therapy, which was manifest as a febrile systemic illness mimicking sepsis. This clinical presentation was potentially indicative of a contaminated intracoronary stent. The patient's signs and symptoms of illness promptly resolved with removal of ticlopidine, and no infection was documented. Review of indications for ticlopidine use, potential adverse effects, and monitoring recommendations are discussed.

High-output heart failure resulting from a remote traumatic aorto-caval fistula: diagnosis by echocardiography.

Congestive heart failure (CHF) due to high output states is known to occur in a variety of systemic illnesses and in patients with arterial-venous fistulas. This paper reports the case of a 45-year-old man admitted to the emergency room with a diagnosis of new onset atrial fibrillation and CHF, whose past medical history was not significant except for a gunshot wound to his abdomen 22 years previously. The etiology of his CHF together with the cardiomegaly and hyperdynamic left ventricular systolic function was unknown. A subcostal view routinely done during transthoracic echocardiography revealed a severely dilated inferior vena cava and the presence of an aorto-caval fistula by color doppler. The patient underwent successful corrective repair with dramatic improvement in symptoms and resolution of the atrial fibrillation, and cardiac size returned to normal. This rare case emphasizes that patients with refractory CHF must be closely examined with particular attention to palpation and auscultation over all scars, irrespective of the duration since any traumatic or surgical event.

Military graduate medical education in internal medicine: an outcomes study.

Military graduate medical education has come under increasing scrutiny in recent years as the size of the military medical force declines. To document the outcomes of military graduate medical education in internal medicine, a cohort of Air Force internal medicine residency graduates from Wright-Patterson Medical Center were studied and their residency performance, staff performance, and active duty retention recorded. The study cohort had an outstanding residency performance, as measured by research experience and board certification rate. They also performed well as military staff physicians, receiving numerous individual military medals while holding important administrative and supervisory positions in the military. Finally, the study cohort had a higher than expected active duty retention rate. These findings support the notion that military graduate medical education in internal medicine produces outstanding military internists.

Regulation of platelet activating factor synthesis: modulation of 1-alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase by phosphorylation and dephosphorylation in rat spleen microsomes.

1-Alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase plays an important regulatory role in the biosynthesis of platelet activating factor, a potent bioactive mediator. We tested the hypothesis that the activity of acetyltransferase may be modulated by enzymatic phosphorylation and dephosphorylation. The results showed that acetyltransferase activity in rat spleens was 2- to 3-fold higher in microsomes isolated in the presence of F-than in those isolated in the presence of Cl-. The microsomal acetyltransferase could be activated by preincubation of microsomes, isolated in the presence of Cl-, with ATP, Mg2+, and the soluble fraction from rat spleen. Addition of phosphatidylserine, diacylglycerols, plus Ca2+ further enhanced the activity. The increase in the activity of acetyltransferase was abolished by treatment of the activated microsomes with alkaline phosphatase. Conversely, the activity of acetyltransferase can be reactivated in the alkaline phosphatase-treated microsomes with incubation conditions that favor phosphorylation. Therefore, our findings suggest that acetyltransferase activity is regulated by reversible activation/inactivation through phosphorylation/dephosphorylation.

Left main coronary artery aneurysm in association with severe atherosclerosis: a case report and review of the literature.

Aneurysms of the coronary arteries occur in from 0.3% to 4.9% of angiograms. Only 12 cases of left main artery (LMA) aneurysms have been reported. Of these, seven were associated with atherosclerosis in patients more than 56 years old. This report details the case of a 39-year-old patient with a large LMA aneurysm associated with atherosclerosis.

Involvement of platelet activating factor in physiological stress in the lizard, Anolis carolinensis.

Platelet activating factor (PAF) and 1-O-alkyl-linked choline-containing phosphoglycerides have been identified in the blood of the lizard, Anolis carolinensis. The level of PAF in the blood of chronically stressed lizards is 250% higher than in that of controls; the blood contains sufficient 1-O-alkyl-linked choline-containing phosphoglycerides to support the synthesis of PAF. Incorporation of PAF is higher in the liver than in the blood; control animals incorporate more PAF than chronically stressed animals. "Lyso"-PAF is the major metabolite in the blood; whereas, in the liver both "lyso"-PAF and "acyl"-PAF are predominant products. 1-Alkyl-2-acetyl-sn-glycero-3-phosphocholine:acetylhydrolase activity in the chronically stressed or corticosterone-implanted lizards is increased 2- to 3-fold over the control. Involvement of PAF in the physiological response to psychological stress is indicated.

Mechanisms, diagnosis, and treatment of diastolic heart failure.

Diastolic heart failure, in the absence of LV systolic dysfunction, is a common clinical condition that can be demonstrated in as many as one third of patients with congestive heart failure. Diastolic dysfunction caused by abnormalities in LV filling can be a result of many pathologic conditions, including hypertrophy, infiltrative cardiomyopathies, or myocardial ischemia. The major physiologic determinants of LV filling can be divided into cellular mechanisms, hemodynamic characteristics, and hormonal influences. Cellular mechanisms for impaired LV inactivation are determined by the handling of calcium within the myocyte during excitation-contraction-relaxation coupling. The hemodynamic characteristics of LV diastolic filling are determined by loading conditions, the time constant of isovolumic relaxation, heart rate, ventricular nonuniformity, pericardial restraint, myocardial elasticity, chamber compliance, and coronary blood flow. The sympathetic nervous system and the renin-angiotensin system are important modulators of diastolic filling, directly or indirectly. The diagnosis of heart failure is confirmed by a combination of clinical tests including invasive and noninvasive techniques, each of which has advantages and disadvantages. Treatment of medical conditions in which diastolic heart failure is a prominent component include pharmacotherapy with calcium channel antagonists, beta-adrenergic blocking agents, diuretic agents, and angiotensin-converting-enzyme inhibitors. Certain conditions associated with diastolic filling abnormalities such as pericardial disease or severe ischemic heart disease may be best managed by surgical or percutaneous intervention. Future research will include further delineation of the cellular mechanisms of active myocardial relaxation and clinical investigation into treatment directed at improving outcome.

Increased biosynthesis of platelet-activating factor in activated human eosinophils.

1-Alkyl-2-lyso-sn-glycero-3-phosphocholine:acetyl-CoA acetyltransferase catalyzes the conversion of biologically inactive lysophospholipid to bioactive platelet-activating factor (1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, PAF) by an acetylation reaction. The activity of this enzyme in eosinophils isolated from patients with eosinophilia is stimulated (up to 4-fold) in a dose-, time-, and Ca2+/Mg2+-dependent manner after exposure to the eosinophil chemotactic factor of anaphylaxis (ECF-A), C5a, formyl-methionylleucylphenylalanine (fMLP), or ionophore A23187. The three naturally occurring chemotactic factors (ECF-A, C5a, and fMLP) cause a rapid and transient increase of enzyme activity, with a maximum at 1 or 3 min, whereas ionophore A23187 maintains an elevated level for up to 15 min. The activity of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine acetylhydrolase, an enzyme that catalyzes the breakdown of PAF to lyso-PAF, is not affected by C5a, fMLP, or ionophore A23187. The presence of PAF in eosinophils was established by demonstrating the lipid nature of the compound, the RF value being identical with that of synthetic 1-hexadecyl-2-acetyl-sn-glycero-3-phosphocholine on thin layer chromatograms, and by its ability to induce serotonin release from rabbit platelets. Furthermore, ECF-A, C5a, fMLP, and ionophore A23187 all induce the secretion of PAF from eosinophils. These findings suggest that the generation and release of PAF could be a consequence of eosinophil chemotactic activation and may thus function in inflammatory and allergic reactions in which eosinophils participate.

Effects of changes in atrioventricular gradient and contractility on left ventricular filling in human diastolic cardiac dysfunction.

The factors responsible for abnormalities in diastolic filling indexes as assessed by noninvasive testing in human beings have been extensively studied but are not completely understood. We therefore investigated left ventricular diastolic filling indexes by radionuclide angiography during right atrial pacing simultaneously with assessment of a directly measured left atrioventricular gradient and a time constant of isovolumic relaxation in 11 patients with hypertension and diastolic dysfunction. Loading conditions were altered with nitroprusside and phenylephrine, and contractility was improved by dobutamine infusion. The maximum left atrioventricular gradient at constant heart rates was determined by loading conditions and was not significantly affected by increases in contractility or an improvement in isovolumic relaxation rate. The peak filling rate according to radionuclide angiography was highly dependent on the atrioventricular gradient and was not affected by enhancement of the isovolumic relaxation rate.

Prediction of human transplantation arteriopathy and coronary events with lung/heart count ratios during intravenous dipyridamole thallium-201 imaging.

BACKGROUND: Cardiac allograft arteriopathy often limits long-term survival in transplantation recipients but has been difficult to detect by standard diagnostic methods. Because of the diffuse nature of transplantation coronary disease, we postulated that a lung/heart ratio during dipyridamole thallium imaging might better predict arteriopathy-related complications than diagnostic methods that detect discrete luminal stenoses. METHODS AND RESULTS: Sixty-six unselected heart transplantation recipients were evaluated with annual coronary arteriograms, endomyocardial biopsy, and intravenous dipyridamole thallium testing (initial study group). The mean lung/heart ratio on an anterior planar image was 0.40 for all patients; therefore <0.40 was arbitrarily defined as normal. After October 1992, 98 patients were tested (validation study group) and a lung/heart ratio cutoff of 0.40 was evaluated prospectively. Coronary end points were defined as (1) at least 1 coronary artery stenosis >/=50% of the luminal diameter, (2) sudden cardiac death, and (3) acute myocardial infarction. Stepwise logistic regression analysis was performed to identify independent predictors of future coronary end points. For the initial study group, the lung/heart ratio on the first annual thallium study was the only independent predictor of subsequent cardiac end points (0.47 +/- 0.13 [SD] with end points vs 0.38 +/- 0.11 without end points, P <.05). For the validation study group, independent predictors of subsequent coronary events included the lung/heart ratio and the radionuclide left ventricular ejection fraction. No patient with a lung/heart ratio <0.40 and a left ventricular ejection fraction >/=0.50 developed a cardiac event during 21 +/- 11 months of follow-up. CONCLUSIONS: A lung/heart ratio >/=0.40 on dipyridamole thallium testing is a sensitive predictor of coronary events after heart transplantation. Patients with heart transplantion who have a lung/heart ratio <0.40 and normal systolic left ventricular function are at low risk for subsequent coronary events and may not require annual surveillance by coronary arteriography.