Is thrombosis a contributor to heart failure pathophysiology? Possible mechanisms,therapeutic opportunities,and clinical investigation challenges

Thrombotic events (coronary thrombosis, venous thromboembolism, intraventricular thrombosis, intracranial and systemic thromboembolism) occur frequently in patients with heart failure. These events may be precipitated by several mechanisms including hypercoagulability through enhancement of procoagulant reactions, impairment of the protein C pathway, protease activated receptor (PAR) activation, adenosine-mediated thrombosis, or neurohormonal activation; stasis secondary to low cardiac output; and endothelial dysfunction from neurohormonal activation or systemic inflammation. Pathophysiologic evidence and analyses of retrospective data support the hypothesis that antithrombotic agents may improve outcomes in patients with heart failure. Warfarin has not been shown to reduce clinical events in patients with heart failure, although several of the completed randomized trials were underpowered, and the most recent was not placebo-controlled. Many unanswered questions remain that justify continued research in this area. This paper examines the conceptual framework, opportunities, and challenges of clinical investigative approaches with the newer anti-thrombotic agents in patients with heart failure. Critical questions are raised with regard to clinical trial designs that warrant consideration as the field progresses.     

Preprocedural white blood cell count and major adverse cardiac events late after percutaneous coronary intervention in saphenous vein grafts

Elevation of white blood cells (WBCs) is associated with worse outcomes in patients with coronary artery disease (CAD), including patients undergoing percutaneous coronary intervention (PCI) of native coronary arteries, but this relation has not been studied in patients with saphenous vein graft disease undergoing PCI. A total of 530 patients who underwent PCI of saphenous vein grafts from May 1997 to July 2002 were followed for >3 years. Major adverse coronary events (MACEs) were assessed as a composite of death, myocardial infarction, or revascularization during follow-up (mean 2.7 years). Patients with MACEs (n = 287) were younger and had more thrombotic and ostial lesions (p < 0.05) than those without MACEs (n = 243). The preprocedural WBC count was also significantly higher in the MACE group than in the non-MACE group (8.1 x 10(3)/mul, range 6.6 to 10.1, vs 7.0 x 10(3)/mul, range 5.6 to 8.2; p < 0.001). After adjusting for covariates, multiple logistic regression analysis revealed the preprocedural WBC count to be an independent predictor for MACEs (odds ratio 1.2; 95% confidence interval 1.1 to 1.3, p < 0.001). Patients in the highest quartile of the preprocedural WBC level had a significantly increased risk of MACEs (lowest vs highest quartile, 41.3% vs 72.4%; odds ratio 3.7; 95% confidence interval 2.2 to 6.3). Thus, an elevated preprocedural WBC count is associated with increased risk of MACEs in patients undergoing PCI for saphenous vein graft lesions.     

Cardiovascular magnetic resonance imaging in asymptomatic patients with connective tissue disease and recent onset left bundle branch block

Background–aim

Recent LBBB in connective tissue diseases (CTDs) is challenging, due to high incidence of underlying pathology that may remain undetected, due to limitations of imaging tests. We hypothesized that cardiovascular magnetic resonance (CMR) may be of diagnostic value in CTDs with recent LBBB and normal echocardiogram.

Patients–methods

26 CTDs, aged 32 ± 7 yrs (19 F) and 26 controls without CTDs, aged 60 ± 4 yrs (10 F) with recent LBBB and normal echo were evaluated by CMR. The CTDs included 6 sarcoidosis (SRC), 4 systemic sclerosis (SSc), 6 systemic lupus erythematosus (SLE), 6 rheumatoid arthritis (RA) and 4 inflammatory myopathies (IM). CMR was performed by 1.5 T. LVEF, T2 ratio (oedema imaging) and late gadolinium enhancement (LGE) (fibrosis imaging) were evaluated. Acute and chronic lesions were characterised by T2 > 2 and positive LGE and T2 < 2 and positive LGE, respectively. According to LGE, lesions were characterised as diffuse subendo-, subepicardial/intramural not following and subendocardial/transmural following the distribution of coronaries, indicative of vasculitis, myocarditis and myocardial infarction, respectively.

Results

CTDs were younger (p < 0.001), with higher incidence of abnormal CMR (42.31 vs 30.77%, p = NS), including dilated cardiomyopathy (11.54%), diffuse subendocardial fibrosis (11.54%), myocardial infarction (7.69%) and acute myocarditis (11.54%) vs dilated cardiomyopathy (19.23%), myocardial infarction (7.69%) and acute myocarditis (3.85%), detected in non-CTDs.

Conclusions

In CTDs with recent LBBB, CMR documented acute and chronic cardiac pathology, particularly myocarditis. CMR should be considered as an adjunct to conventional diagnostic workup in both patient groups, more so in CTDs.     

An unclassified tibial plateau fracture: Reverse Schatzker type IV

The most commonly accepted system of classification for tibia plateau fractures is that of Schatzker. Increasingly, both high energy injuries and atypical osteoporotic fragility failures have led to more complex, unusual and previously undescribed fracture patterns being recognized. We present a case of a patient with a previously unreported pattern of tibia plateau fracture and knee dislocation. We highlight the challenges confronted and present the management and the outcomes of his injury. A 28-year old male motorcyclist was involved in a head on collision with a truck and was transferred by helicopter to our level 1 major trauma centre emergency department. His injuries were a circumferential degloving injury to his left leg and a right lateral tibial plateau fracture/knee dislocation. The pattern of the lateral tibial plateau fracture was unique and did not fit any recognised classification system. The patient received a spanning external fixator initially and after latency of 12 days for soft tissue resuscitation he underwent definite fixation through an antero-lateral approach to the proximal tibia with two cannulated 6.5 mm partially threaded screws and an additional lateral proximal tibia plate in buttress mode. A hinged knee brace was applied with unrestricted range of motion post-operatively and free weight bearing were permitted post operatively. At the 6 months follow up, the patient walks without aids and with no limp. Examination revealed a stable joint and full range of motion. Plain radiographs revealed that the fracture healed with good alignment and the fixation remained stable. High energy injuries can lead to more complicated fracture patterns, which challenge the orthopaedic surgeons in their management. It is crucial to understand the individual fracture pattern and the possible challenges that may occur. This study reports a lateral tibia plateau fracture/dislocation which perhaps is best described as a reverse Schatzker IV type fracture.