Carfilzomib and the cardiorenal system in myeloma: an endothelial effect?

Carfilzomib (Cfz) has been associated with an ~5% incidence of unexplained and unpredictable cardiovascular toxicity in clinical trials. We therefore implemented a detailed, prospective, clinical cardiac and renal evaluation of 62 Cfz-treated myeloma patients, including serial blood pressure (BP), creatinine, troponin, NT-proBNP and pre- and post-treatment echocardiograms, including ejection fraction (EF), average global longitudinal strain and compliance. Pre-treatment elevations in NT-proBNP and BP, as well as abnormal cardiac strain were common. A rise in NT-proBNP occurred frequently post-treatment often without corresponding cardiopulmonary symptoms. A rise in creatinine was common, lessened with hydration and often reversible. All patients had a normal EF pre-treatment. Five patients experienced a significant cardiac event (four decline in EF and one myocardial infarction), of which 2 (3.2%) were considered probably attributable to Cfz. None were rechallenged with Cfz. The ideal strategy for identifying patients at risk for cardiac events, and parameters by which to monitor for early toxicity have not been established; however, it appears baseline echocardiographic testing is not consistently predictive of toxicity. The toxicities observed suggest an endothelial mechanism and further clinical trials are needed to determine whether or not this represents a class effect or is Cfz specific.

Therapeutic goals in patients with pheochromocytoma: a guide to perioperative management.

INTRODUCTION: Pheochromocytomas are rare neuroendocrine tumors of the adrenal medulla that may present with protean manifestations. Surgical resection is the mainstay of therapy and patients are at risk of significant hemodynamic and circulatory complications mainly attributable to catecholamine excess. The mainstay of medical therapy in order to optimize patients for surgery includes: alpha-blockers, beta-blockers, calcium channel blocker and other agents to achieve normal blood pressure, heart rate, as well as normal volume status. Understanding the pathophysiology of pheochromocytoma, the pharmacology of medications used, and recognizing postoperative complications will impact patient outcomes. CONCLUSION: A multidisciplinary team approach is best throughout the perioperative period to prevent potential complications that arise. The hospital physician, intensivist, anesthetist and cardiovascular specialist play a pivotal role in the management of patients with pheochromocytoma. In addition to the pharmacologic and volume recommendations, a multidisciplinary discussion allows for seamless implementation of an organized plan of care.

Clinical relevance of myocardial bridging severity: single center experience.

BACKGROUND: Myocardial bridging refers to intramyocardial systolic compression of a segment of an epicardial coronary artery. We aimed to identify the clinical significance of myocardial bridging by assessing the clinical presentation in non-obstructive coronary artery disease among a cohort of consecutive patients presenting for coronary angiography. MATERIALS AND METHODS: A retrospective review of our institution's database between September 2002 and March 2005 was conducted to review coronary angiography reports of 14,416 patients. The study group included 226 patients (prevalence=1.57%) with isolated myocardial bridging and <50% stenosis in the non-bridged arteries. Cases with myocardial bridging were classified according to the percentage of systolic compression of the left anterior descending artery into group I (<50% compression), group II (50-70% compression) and group III (compression >or= 70%). RESULTS: Mean age was 57.6+/-15.5 years; 59% were men. The mean duration of follow-up was 12+/-2 months. The left anterior descending was the most common site of bridging (210, 93%). There was a significant difference between groups I and III with respect to the percentage of patients who presented with non-fatal myocardial infarction (P=0.02). Unstable angina had the highest association with myocardial bridging, but there was no significance among the level of myocardial bridging severity and the clinical presentation of angina. CONCLUSIONS: Myocardial bridging is not a benign variation of coronary anatomy. It is associated with angina and myocardial infarction in patients with >or= 70% systolic compression. The bridged segment may be a cause of enhanced atherosclerotic plaque formation.

Valvular regurgitation and stenosis: when is surgery required?

Valvular heart disease is a growing public health problem, with an increasing prevalence due to an ageing population. Despite advances, the medical management of symptomatic valvular heart diseases remains suboptimal, necessitating surgical correction. The challenge remains in identifying an asymptomatic or mildly symptomatic patient who will benefit from timely surgery before irreversible changes in cardiac function have occurred. The potential risks of surgery versus watchful expectancy require careful decision-making. This review is a focused update on the existing guidelines and identifies the knowledge gaps and avenues of future research in the management of patients with valvular heart diseases.

The association between the timing of valve surgery and 6-month mortality in left-sided infective endocarditis.

OBJECTIVE: The optimal timing of valve surgery in left-sided infective endocarditis (IE) is undefined. We aimed to examine the association between the timing of valve surgery after IE diagnosis and 6-month mortality among patients with left-sided IE. METHODS: We analysed data from a retrospective cohort of patients with left-sided IE who underwent valve surgery within 30 days of diagnosis at a tertiary centre. The association between time from IE diagnosis to surgery and all-cause 6-month mortality was assessed using Cox proportional hazards modelling after adjusting for the propensity score (to undergo surgery 0-11 days vs >11 days, median time, after IE diagnosis). RESULTS: Of 546 left-sided IE cases seen between 1980 and 1998, 129 (23.6%) underwent valve surgery within 30 days of diagnosis. The median time between IE diagnosis and surgery was 11 days (range 1-30). There were 35/129 (27.2%) deaths in the surgical group. Using Cox proportional hazards modelling, propensity score and longer time to surgery (in days) were associated with unadjusted HRs of (1.15, 95% CI 1.04 to 1.28, per 0.10 unit change, p = 0.009) and (0.93; 95% CI 0.88 to 0.99, per day, p = 0.03), respectively. In multivariate analysis, a longer time to surgery was associated with an adjusted HR (0.97; 95% CI 0.90 to 1.03). The propensity score and time from diagnosis to surgery had a correlation coefficient of r = -0.63, making multicollinearity an issue in the multivariable model. CONCLUSION: On univariate analysis, a longer time to surgery showed a significant protective effect for the outcome of mortality. After adjusting for the propensity to undergo surgery early versus late, a longer time to surgery was no longer significant but remained in the protective direction. Multicollinearity between the time to surgery and the propensity score may have hindered our ability to detect the independent effect of time to surgery.

Corynebacterium jeikeium endocarditis: a systematic overview spanning four decades.

Skin flora is an important source of microorganisms that cause infective endocarditis. While staphylococcal and beta-hemolytic streptococcal species are well-recognized components of skin flora that can cause infective endocarditis, other skin flora rarely produce endocardial infection. One species of Corynebacterium has received the most attention, Corynebacterium jeikeium. This bacterium, a gram-positive rod that is a strict aerobe, is known to cause mechanical prosthetic valve infection and vancomycin is generally required for treatment of this multidrug-resistant organism. Following treatment of an unusual case of bioprosthetic valve endocarditis due to C. jeikeium, a Medline search for English-language articles published from January 1966 to October 2004 was performed. Reports of C. jeikeium endocarditis cases with culture of either blood or cardiac surgery tissue samples positive for C. jeikeium and with clinical and echocardiographic findings of infective endocarditis were reviewed. Clinical data and results of diagnostic procedures were examined. All 38 patients with C. jeikeium endocarditis reported in the literature had at least one predisposing condition for the development of infective endocarditis. The majority of patients (74%) had involvement of a prosthetic heart valve. The mortality attributed to C. jeikeium endocarditis was 33% and was similar in patients who did and did not undergo valve replacement. This relatively high mortality rate mandates that clinicians be aware of this rare endocardial infection. C. jeikeium is a rare cause of endocarditis and it more commonly infects prosthetic valves. Careful scrutiny is required when C. jeikeium is isolated from a blood culture, particularly in patients with underlying prosthetic cardiac valves.

Rare cause of right heart failure: contained rupture of a sinus of Valsalva aneurysm associated intraventricular septal aneurysm.

Sinus of Valsalva aneurysm (SVA) is a rare congenital lesion described first in 1840 by John Thurnam (Cited by Boutefou JM, Moret PR, Hahn C, Hanf E. Aneurysms of the sinus of Valsalva: report of seven cases and review of the literature. Am J Med 1978;65:18-24). In most cases unruptured Sinus of Valsalva aneurysm (SVA) is clinically silent; however, if it progressively enlarges it may cause coronary artery compression, complete heart block, or right ventricular outflow tract obstruction (Meier JH, Seward JD, Miller FA, Oh J, Sarano ME. Aneurysms in the left ventricular outflow tract: clinical presentation, causes, and echocardiographic features. J Am Soc Echocardiogr 1998;11:729-45; D'Silva SA, Dalve BV, Lokhandwala YY, Kale PA, Tendolkar AG. Unruptured congenital aneurysm of the left sinus of Valsalva presenting as acute right heart failure. Chest 1992;101:578-79) or is a potential source of cerebrovascular emboli. (Shahrabani RM, Jairaj PS. Unruptured aneurysm of the sinus of Valsalva: a potential source of cerebrovascular embolism. Br Heart J 1993;69:266-67). In this report, we describe a case of right coronary sinus of Valsalva aneurysm with a contained rupture. The containing rupture is in intraventricular septal aneurysm; the patient presents with right-sided heart failure.

Enterococcus avium endocarditis.

We describe a rare case of Enterococcus avium endocarditis in a patient with an ovarian malignancy, and review 2 previously reported cases. We contend that Enterococcus avium bacteremia and endocarditis may be associated with gastrointestinal pathology.

Calcified bicuspid aortic valve mass prolapsing into the left main coronary artery.

We report a case of a mobile calcific mass on the aortic valve that prolapsed into the left main coronary artery of a 51-year-old man. This case and a review of the literature suggest that calcific embolization to coronary arteries is a rare but possibly underrecognized complication of calcified degenerative or bicuspid aortic valves. This potentially catastrophic complication of calcified aortic valves needs to be suspected and recognized in clinical practice.

Multidisciplinary education for oxygen prescription. A continuous quality improvement study.

OBJECTIVES: To examine the oxygen-prescribing habits and monitoring patterns on a medical teaching ward and to review the literature in this area. DESIGN: A continuous quality improvement study. SETTING: A 29-bed medical clinical teaching unit in a 453-bed university-affiliated tertiary care hospital. PATIENTS: We studied 50 consecutive patients who required 79 oxygen treatments. METHODS: We recorded the indication, prescriber, documentation of prior hypoxemia, method and mode of delivery, oxygenation assessment after initiation, and duration of therapy. RESULTS: Patients received oxygen for a mean (+/- SD) of 4.7 +/- 4.5 days. Oxygen therapy was ordered on a continuous basis 60.3% of the time. It was ordered by house staff in 54 cases (68%); nurses initiated oxygen therapy in 14 cases (18%) but discontinued it more often than any other health care workers. The most common indications for starting oxygen therapy were dyspnea and tachypnea. In 15 patients (30%), none of the American College of Chest Physicians and National Heart, Lung, and Blood Institute criteria for starting oxygen therapy were fulfilled. For 16 patients (32%), arterial blood gas values were measured within 1 hour of oxygen administration; for 29 patients, oximetry was performed. For 9 patients (18%), no testing of adequate oxygenation was performed within 24 hours. Oxygenation status was assessed daily for 23 patients (46%). CONCLUSIONS: Oxygen prescribing and monitoring practices were suboptimal on our busy medical teaching ward. Practice guidelines based on best available evidence are needed to increase the efficiency of oxygen use. A physiologic, multidisciplinary educational focus on the benefits and hazards of supplemental oxygen is necessary, and randomized trials of such educational interventions should be conducted.