Zaid Alirhayim

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.

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

Abstract 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.

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. Liver Transpl 19:701–710, 2013.

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.

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.

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.

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.

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.

DRESS syndrome and thrombotic thrombocytopaenic purpura: are they related?

A middle-aged man diagnosed with a drug reaction with eosinophilia and systemic symptom (DRESS) syndrome, secondary to phenytoin use, subsequently developed thrombotic thrombocytopaenic purpura. The patient improved with steroids and plasmapheresis. Their diagnosis can be challenging, and an early recognition and treatment are critical owing to their high mortality rates. Both diseases are thought to be of an autoimmune origin, and a potential relationship between them led to the consideration of the DRESS syndrome as an aetiology for thrombotic thrombocytopaenic purpura in this case. We concluded that two possibilities exist: some type of antibody developed during the clinical presentation of DRESS syndrome and subsequently resulted in an inhibition of a disintegrin and metalloproteinase with a thrombospondin type-1 motif, member 13 (ADAMTS13) leading to thrombotic thrombocytopaenic purpura, or perhaps this patients autoimmune predisposition to thrombotic thrombocytopaenic purpura contributed to the drug reaction.

Response to Letter Regarding Article, “Cardiorespiratory Fitness and Risk of Incident Atrial Fibrillation: Results From the Henry Ford Exercise Testing (FIT) Project”

We thank Dr Patane for the kind words. We agree that obstructive sleep apnea and ectopic adipose tissue deposition (eg, pericardial fat) are important risk factors for the development of atrial fibrillation (AF). Recently, both mechanisms have been suggested to have a causal effect through various paracrine and mechanical pathways. Most of our knowledge in this regard is drawn from animal models, and a recent Australian study demonstrated that overfed obese sheep with …