Brain Natriuretic Peptide as a Marker of Adverse Neurological Outcomes Among Survivors of Cardiac Arrest.

BACKGROUND: Neurological prognosis after cardiac arrest remains ill-defined. Plasma brain natriuretic peptide (BNP) may relate to poor neurological prognosis in brain-injury patients, though it has not been well studied in survivors of cardiac arrest. METHODS: We performed a retrospective review and examined the association of BNP with mortality and neurological outcomes at discharge in a cohort of cardiac arrest survivors enrolled from January 2012 to December 2016 at the Wake Forest Baptist Hospital, in North Carolina. Cerebral performance category (CPC) and modified Rankin scales were calculated from the chart based on neurological evaluation performed at the time of discharge. The cohort was subdivided into quartiles based on their BNP levels after which multivariable adjusted logistic regression models were applied to assess for an association between BNP and poor neurological outcomes as defined by a CPC of 3 to 4 and a modified Rankin scale of 4 to 5. RESULTS: Of the 657 patients included in the study, 254 patients survived until discharge. Among these, poor neurological status was observed in 101 (39.8%) patients that had a CPC score of 3 to 4 and 97 patients (38.2%) that had a modified Rankin scale of 4 to 5. Mean BNP levels were higher in patients with poor neurological status compared to those with good neurological status at discharge (P = .03 for CPC 3-4 and P = .02 for modified Rankin score 4-5). BNP levels however, did not vary significantly between patients that survived and those that expired (P = .22). BNP did emerge as a significant discriminator between patients with severe neurological disability at discharge when compared to those without. The area under the curve for BNP predicting a modified Rankin score of 4 to 5 was 0.800 (95% confidence interval [CI] 0.756-0.844, P < .001) and for predicting CPC 3 to 4 was 0.797 (95% CI 0.756-0.838, P < .001). BNP was able to significantly improve the net reclassification index and integrated discriminatory increment (P < .05). BNP was not associated with long-term all-cause mortality (P > .05). CONCLUSIONS: In survivors of either inpatient or out-of-hospital cardiac arrest, increased BNP levels measured at the time of arrest predicted severe neurological disability at discharge. We did not observe an independent association between BNP levels and long-term all-cause mortality. BNP may be a useful biomarker for predicting adverse neurological outcomes in survivors of cardiac arrest.

Cardiorespiratory Fitness and Risk of Incident Atrial Fibrillation: Results From the Henry Ford Exercise Testing (FIT) Project.

BACKGROUND: Poor cardiorespiratory fitness (CRF) is an independent risk factor for cardiovascular morbidity and mortality. However, the relationship between CRF and atrial fibrillation (AF) is less clear. The aim of this analysis was to investigate the association between CRF and incident AF in a large, multiracial cohort that underwent graded exercise treadmill testing. METHODS AND RESULTS: From 1991 to 2009, a total of 64 561 adults (mean age, 54.5±12.7 years; 46% female; 64% white) without AF underwent exercise treadmill testing at a tertiary care center. Baseline demographic and clinical variables were collected. Incident AF was ascertained by use of International Classification of Diseases, Ninth Revision code 427.31 and confirmed by linkage to medical claim files. Nested, multivariable Cox proportional hazards models were used to estimate the independent association of CRF with incident AF. During a median follow-up of 5.4 years (interquartile range, 3-9 years), 4616 new cases of AF were diagnosed. After adjustment for potential confounders, 1 higher metabolic equivalent achieved during treadmill testing was associated with a 7% lower risk of incident AF (hazard ratio, 0.93; 95% confidence interval, 0.92-0.94; P<0.001). This relationship remained significant after adjustment for incident coronary artery disease (hazard ratio, 0.92; 95% confidence interval, 0.91-0.93; P<0.001). The magnitude of the inverse association between CRF and incident AF was greater among obese compared with nonobese individuals (P for interaction=0.02). CONCLUSIONS: There is a graded, inverse relationship between cardiorespiratory fitness and incident AF, especially among obese patients. Future studies should examine whether changes in fitness increase or decrease risk of atrial fibrillation. This association was stronger for obese compared with nonobese, especially among obese patients.

Prognostic value of extracardiac incidental findings on attenuation correction cardiac computed tomography.

BACKGROUND: Attenuation corrected computed tomography (CTAC) is often performed to improve the specificity of single-photon emission tomography imaging. Extracardiac incidental findings are frequently observed. It is unclear whether these findings have any prognostic value. METHODS: Consecutive patients (n = 1139) at a tertiary care center were retrospectively evaluated for incidental findings on CTAC. Clinically significant incidental findings were defined as findings warranting physician follow-up. Information regarding subsequent resource utilization was obtained by chart review. Cox proportional hazard model adjusted for demographic and clinical variables was used to evaluate association of these incidental findings with all-cause and cancer-specific mortality. RESULTS: A total of 135 (12%) patients with incidental findings were identified, 83 of whom (68%) were newly diagnosed. Lung nodules were the most common finding, present in 92 (68%) patients. Over a median follow-up of 468 days, incidental findings were not significantly associated with increased risk of all-cause mortality (HR 1.34; 95% CI 0.77-2.33, P = 0.29) but was significantly associated with cancer-specific mortality (HR 3.21; 95% CI 1.26-8.14, P = 0.01). This association remained statistically significant when the analysis was limited to newly diagnosed incidental findings. Among patients with incidental findings, follow-up radiographic studies were conducted in 87%, and invasive procedures performed in 32%. Physician office-based follow-up of these findings occurred in 42% of patients and incidental finding-related hospitalization occurred in 14%. CONCLUSIONS: This study shows that incidental findings are common and were associated with all-cause and cancer-specific mortality but only the later remained statistically significant after multivariable adjustment.

Late Migration of a Transcatheter Heart Valve.

Migration or embolization of transcatheter aortic valve replacement (TAVR) prosthesis is an uncommon (usually acute) complication. Associated risk factors include malpositioning, pacing miscapture, undersizing, postdilation, and bicuspid anatomy. Delayed migration is exceedingly rare with little experience reported. The presentation can be catastrophic, requiring emergency surgery. Herein, we present a case of late TAVR migration managed with repeat transfemoral TAVR.

Clinical predictors of post-liver transplant new-onset heart failure.

Objectives of this study were (1) to evaluate preoperative predictors of systolic and diastolic heart failure in patients undergoing liver transplantation (LT) and (2) to describe the prognostic implications of systolic and diastolic heart failure in these patients. The onset of heart failure after orthotopic LT remains poorly understood. Data were obtained for all LT recipients between January 2000 and December 2010. The primary outcome was post-LT heart failure: systolic (ejection fraction ≤ 50%), diastolic, or mixed heart failure. Patients underwent echocardiographic evaluation before and after LT. Pretransplant variables were evaluated as predictors of heart failure with Cox proportional hazards model. 970 LT recipients were followed for 5.3 ± 3.4 years. Ninety-eight patients (10.1%) developed heart failure in the posttransplant period. There were 67 systolic (6.9%), 24 diastolic (2.5%), and 7 mixed systolic/diastolic (0.7%) heart failures. Etiology was ischemic in 18 (18.4%), tachycardia-induced in 8 (8.2%), valvular in 7 (7.1%), alcohol-related in 4 (4.1%), hypertensive heart disease in 3 (3.1%), and nonischemic in majority of patients (59.2%). Pretransplant grade 3 diastolic dysfunction, diabetes, hypertension, mean arterial pressure ≤ 65 mm Hg, mean pulmonary artery pressure ≥ 30 mm Hg, mean pulmonary capillary wedge pressure ≥ 15 mm Hg, hemodialysis, brain natriuretic peptide level and QT interval > 450 ms were found to be predictive for the development of new-onset systolic heart failure. However beta-blocker use before LT and tacrolimus after LT were associated with reduced development of new-onset systolic heart failure. In conclusion, pretransplant risk factors, hemodynamic variables, and echocardiographic variables are important predictors of post-LT heart failure. In patients undergoing LT, postoperative onset of systolic or diastolic heart failure was found to be an independent predictor of mortality.

Heparin-induced thrombocytopenia: is it a graft-threatening complication?

Heparin-induced thrombocytopenia (HIT), a prothrombotic complication of heparin therapy, can lead to serious thromboembolic events and cause significant morbidity and mortality. We aim to study the prevalence of HIT in the transplant population at our institute. This is a retrospective, single-center study which looked into the transplant database over a 25-year period. In patients with clinical suspicion of HIT, the 4T score was used, and laboratory tests such as ELISA HIT antibody and functional serotonin release assay, along with clinical manifestation of thromboembolic events were reviewed. Medical records of 2800 patients who underwent transplantation from January 1985 to December 2010 were reviewed. HIT antibody assay was performed in 262 patients from this group in which HIT was suspected. Of these, only 48 patients were HIT antibody positive along with moderate to high 4T score. The mean 4T score was 6.75 ± 1.4. Thrombotic complications were seen in 11 patients, with the highest in cardiac transplant recipients. Direct thrombin inhibitor (DTI) therapy was used in only eight patients who had thrombotic event. No other complications or mortality was reported in any of the HIT antibody-positive transplant patients. To our knowledge, this is the first study of its kind that has shown very low incidence of HIT in the transplant population except for in cardiac transplant recipients.

Impact of restarting warfarin therapy in renal disease anticoagulated patients with gastrointestinal hemorrhage.

BACKGROUND: Atrial fibrillation (AF) is emerging as a major health problem. The prevalence is as high as 32% in patients with renal disease. Gastrointestinal bleeding (GIB) is a frequent complication. OBJECTIVE: To investigate the hazards of resumption or discontinuation of anticoagulation in renal disease patients after an episode of GIB. DESIGN, SETTINGS, PARTICIPANTS AND MEASUREMENTS: This is a multicenter retrospective cohort of patients with AF on warfarin that developed an episode of GIB. Chronic kidney disease (CKD) was defined by eGFR ≤60 mL/min and end stage renal disease (ESRD) was defined by being on hemodialysis for >3 months. Outcomes were 90-day recurrent gastrointestinal bleeding (GIB), mortality, and stroke/transient ischemic attack (TIA). RESULTS: Out of 11,513 AF patients, index GIB occurred in 96 ESRD and 159 CKD patients. Outcomes of CKD patients did not differ when compared with patients with normal kidney function. CKD patients who resumed warfarin had decreased stroke/TIA rates (p < 0.0001). There were no significant differences between CKD patients who resumed warfarin versus that did not resume warfarin (p > 0.05). ESRD patients also did not have significant differences in outcomes when compared to patients with normal kidney function restarted on warfarin. However, there was an increase in recurrent GIB and decrease in mortality as well as stroke/TIA when patients with ESRD that restarted warfarin were compared with ESRD patients who did not restart warfarin. CONCLUSION: Study suggests resuming warfarin after an episode of GIB in CKD patients but recommends considering the increased risk of recurrent GIB in ESRD patients.

Venous Thromboembolism in Cancer: An Update of Treatment and Prevention in the Era of Newer Anticoagulants.

Cancer patients are at major risk of developing venous thromboembolism (VTE), resulting in increased morbidity and economic burden. While a number of theories try to explain its pathophysiology, its risk stratification can be broadly done in cancer-related, treatment-related, and patient-related factors. Studies report the prophylactic use of thrombolytic agents to be safe and effective in decreasing VTE-related mortality/morbidity especially in postoperative cancer patients. Recent data also suggest the prophylactic use of low molecular weight Heparins (LMWHs) and Warfarin to be effective in reducing VTEs related to long-term central venous catheter use. In a double-blind, multicenter trial, a new ultra-LMWH Semuloparin has shown to be efficacious in preventing chemotherapy-associated VTE's along with other drugs, such as Certoparin and Nadoparin. LMWHs are reported to be very useful in preventing recurrent VTEs in advanced cancers and should be preferred over full dose Warfarin. However, their long-term safety beyond 6 months has not been established yet. Furthermore, this paper discusses the safety and efficacy of different drugs used in the treatment and prevention of recurrent VTEs, including Bemiparin, Semuloparin, oral direct thrombin inhibitors, parenteral and direct oral factor Xa inhibitors.

Symptomatic ileofemoral deep vein thrombosis due to May-Thurner syndrome.

A 33-year-old woman with no medical history reported an acute onset of left leg and thigh swelling. A review of her medications revealed that she had started oral contraceptives 2 months previously. Ultrasonography and subsequent venography demonstrated extensive ileofemoral clot burden. Thrombolysis and thrombectomy successfully restored venous return with subsequent improvement in the leg swelling and oedema. In this case, we describe a patient presenting with extensive ileofemoral deep vein thrombosis, otherwise known as the May-Thurner syndrome.

Restarting anticoagulation and outcomes after major gastrointestinal bleeding in atrial fibrillation.

Data regarding the outcomes of restarting anticoagulation in patients who develop gastrointestinal bleeding (GIB) while anticoagulated are sparse. We hypothesized that restarting anticoagulation in these patients is associated with better outcomes. This is a retrospective cohort study that enrolled subjects who developed GIB while on anticoagulation from 2005 to 2010. Atrial fibrillation was defined by history and electrocardiography on presentation. GIB was defined as a decrease in hemoglobin by 2 g, visible bleeding, or positive endoscopic evaluation. Time-to-event adjusted analyses were performed to find an association of restarting warfarin and recurrent GIB, arterial thromboembolism, and mortality. Stratified analysis by duration of interruption of warfarin was also performed. Overall, 1,329 patients (mean age 76 years, women 45%) developed major GIB. Warfarin was restarted in 653 cases (49.1%). Restarting warfarin was associated with decreased thromboembolism (hazard ratio [HR] 1.18, 95% confidence interval [CI] 0.75 to 1.84, p = 0.47) [corrected] and reduced mortality (HR 0.67, 95% CI 0.56 to 0.81, p <0.0001) but not recurrent GIB (HR 1.18, 95% CI 0.94 to 1.10, p = 0.47). When the outcomes were stratified by duration of warfarin interruption, restarting warfarin after 7 days was not associated with increased risk of GIB but was associated with decreased risk of mortality and thromboembolism compared with resuming after 30 days of interruption. Decision to restart warfarin after an episode of major GIB is associated with improved survival and decreased thromboembolism without increased risk of GIB after 7 days of interruption.

Interplay of parathyroid hormone and aldosterone antagonist in prevention of heart failure hospitalizations in chronic kidney disease.

BACKGROUND: Aldosterone antagonists may mediate their effects on heart failure through parathyroid hormone (PTH) in chronic kidney disease (CKD) patients. METHODS: Patients with CKD on spironolactone were selected and matched for age, gender, race, use of a vitamin D analogue, the number of antihypertensive medications, and CKD stage. PTH levels before and after the first prescription of spironolactone were measured. A thorough chart review was conducted to assess for heart failure hospitalizations. An adjusted Cox proportional model was used to calculate the hazard ratio (HR) for heart failure hospitalizations among cases versus controls. RESULTS: There were a total of 950 (mean age 67±13 years, 40% men) patients with CKD. Of these, there were 48 hospitalizations for heart failure among the cases and 82 among the controls (HR 0.37; 95% confidence interval (CI) 0.19-0.74, p=0.005). We noted a more significant decrease in PTH levels among the cases when compared to the controls (p<0.0001). The adjusted hazard for heart failure hospitalization increased with higher PTH levels (p=0.002) and mediation analysis revealed change in PTH level as a significant mediator of heart failure hospitalization (p=0.04). CONCLUSION: Aldosterone antagonists may be helpful in preventing hospitalizations for heart failure exacerbation in CKD patients through a PTH-mediated effect.

Cryofibrinogenaemia: not just skin deep.

A Caucasian woman in her 60s with a history of rheumatoid arthritis presented to our institution complaining of skin ulceration. Her initial course was complicated by superinfection and sepsis until a diagnosis of cryofibrinogenaemia was finally established. Cryofibrinogenaemia remains as an under-recognised entity in part, because it can mimic other causes of skin ulcerations. In addition, its diagnosis can be challenging because of the particular handling techniques required of lab specimens. This case exemplifies some of the diagnostic and treatment challenges encountered while managing the patient with cryofibrinogenaemia.

Non-Hodgkin's lymphoma: a cause of paraneoplastic cholestasis.

We describe a 79-year-old gentleman with a longstanding history of chronic lymphocytic leukaemia who presented with subacute onset of cholestatic jaundice. Comprehensive review of the patient's data and medications failed to reveal any obvious causes. Exhaustive testing including abdominal CT and magnetic resonance cholangiopancreatography failed to reveal any obstruction. A liver biopsy demonstrated scattered non-caseating granulomas. The patient was diagnosed with granulomatous hepatitis and treated with oral steroids and eventually improved. It was thought to be due to paraneoplastic cholestasis as an extrahepatic manifestation of non-Hodgkin's lymphoma.

Lithium toxicity in the setting of nonsteroidal anti-inflammatory medications.

Lithium toxicity is known to affect multiple organ systems, including the central nervous system. Lithium levels have been used in the diagnosis of toxicity and in assessing response to management. There is evidence that nonsteroidal anti-inflammatory medications (NSAIDs) can increase lithium levels and decrease renal lithium clearance. We present a case of lithium toxicity, which demonstrates this effect and also highlights the fact that lithium levels do not correlate with clinical improvement, especially the neurological deficit.

Polyoma BK Virus: An Oncogenic Virus?

We report a case of a 65-year-old gentleman with a history of end stage renal disease who underwent a successful cadaveric donor kidney transplant four years ago. He subsequently developed BK virus nephropathy related to chronic immunosuppressant therapy. Three years later, misfortune struck again, and he developed adenocarcinoma of the bladder.

Aortic arch variant presenting as an acute ST elevation myocardial infarction.

A woman in her 40s presented to our institution with a first episode of sudden-onset right-sided chest pain. Initially, her ECG revealed ST segment elevation in leads V1-V3 and cardiac biomarkers were elevated with a troponin I (TnI) 5 µg/l. Her cardiac risk factors included type II diabetes mellitus and a history of hypertension. Intravenous heparin was initiated and emergent cardiac catheterisation revealed non-obstructive coronary artery disease. A two-dimensional echocardiogram confirmed hypokinesis of the anterior wall. A CT thorax demonstrated a rare anatomical variant of the aortic arch with an aberrant right subclavian artery. This is a rare case of an aortic arch anomaly presenting as a myocardial infarction.

Treating symptomatic coronary artery disease in patients with Von Willebrand disease.

There is limited data on the occurrence of coronary artery disease (CAD) in patients with Von Willebrand disease and the literature is even scarce on their management. We at our institute reviewed the medical records of 198 patients with Von Willebrand disease over a period of 15years, of which 6 were found to have symptomatic CAD. Acute coronary syndrome was noted in 3 patients while the remaining 3 had stable angina. Cardiac catheterization showed that left main coronary artery was the culprit vessel in all of these patients. In terms of management, stents were placed in 3 patients, two of them underwent coronary artery bypass grafting, and the remaining one patient was medically managed. Aspirin, and in some patients clopidogrel, was well tolerated with minimal side effects.

Outcomes of correcting hyponatremia in patients with myocardial infarction.

BACKGROUND: Hyponatremia has significant prognostic implications in patients with heart, failure. However, little data are available regarding its significance in patients presenting with myocardial infarction. In addition, it is not known if correction of hyponatremia impacts outcomes in these patients. The aim of this study was to evaluate the prognostic value of hyponatremia in patients with myocardial infarction and the effect of its correction on all-cause mortality. METHODS: Patients with the discharge diagnosis of myocardial infarction at our institution between 2000 and 2010 with serum sodium levels measured within 24 h of admission were included in this retrospective analysis. Multivariate analysis was used to determine the predictors of all-cause mortality. Cox proportional hazard model was applied to determine the adjusted survival. RESULTS: A total of 11,562 patients (67.15 ± 14.6 years, males 56.3 %) were included in the analysis. There were a total of 1,535 (13.3 %) deaths within mean follow-up duration of 5.5 ± 3.3 years. There were 425 (27.9 %) deaths in patients with corrected hyponatremia and 155 (55.3 %) deaths in persistent hyponatremia patients. Multivariate analysis indicated that corrected hyponatremia and persistent hyponatremia were independent predictors of all cause mortality (p < 0.0001). When analyzing short-term (30 days) and long-term mortality, corrected hyponatremia group did not have associated long term mortality. Various methods to correct hyponatremia were also analyzed and use of vaptans was associated with decrease in mortality in patients with hyponatremia from 115 to 125 (HR 0.45; 95 % CI 0.26-0.78, p = 0.005). CONCLUSION: Our analysis showed that corrected and persistent hyponatremia in patients presenting with myocardial infarction is a predictor of all-cause mortality, major adverse cardiac events and heart failure related 30 day rehospitalization. In certain cases, correction of hyponatremia may actually improve survival of the patients.