Tommy Chung

Long-Term Cardiovascular and Noncardiovascular Mortality of 1023 Patients With Confirmed Acute Pulmonary Embolism

Background— There are currently no guidelines advising long-term surveillance of patients following an acute pulmonary embolism (PE), because long-term outcome studies are rare. We investigated the long-term cardiovascular and all-cause mortality of a large patient cohort with confirmed PE in relation to baseline cardiovascular disease (CVD). Methods and Results— Clinical details of all patients presenting with acute PE to a tertiary hospital were retrieved from medical records, and their survival tracked from a statewide death registry. There were 1023 (45% males) patients admitted with confirmed PE from 2000 to 2007. During a mean follow-up of 3.8±2.6 years, 363 patients died (35.5%), of whom only 31 (3.0%) died in-hospital during the index PE admission. The 3-month, 6-month, 1-year, 3-year, and 5-year cumulative mortality rates were 8.3%, 11.1%, 16.3%, 26.7%, and 31.6% respectively. Annual mortality did not improve over the 7-year period. The postdischarge mortality of 8.5%/patient-year was 2.5-fold that of an age- and sex-matched general population, being 12.6-fold in the youngest quintile (<55 years) and 1.9-fold in the oldest quintile (≥83 years). Patients with known CVD at baseline had 2.2-fold greater all-cause mortality than those without CVD, and this effect, although at a lower level of risk, remained significant after multivariate analysis. Of the 332 deaths occurring postdischarge, 40% were attributed to cardiovascular causes. Conclusions— In a contemporary adult population, PE is associated with a substantially increased long-term mortality, of which nearly half is cardiovascular. Our study highlights the urgent need to develop long-term surveillance strategies in this population.

Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel

Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activation within human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel. A novel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined. We provide evidence of intracoronary up-regulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.

Effects of testosterone and nandrolone on cardiac function: a randomized, placebo-controlled study

Background  Androgens have striking effects on skeletal muscle, but the effects on human cardiac muscle function are not well defined, neither has the role of metabolic activation (aromatization, 5α reduction) of testosterone on cardiac muscle been directly studied.

Prognostic Impact of the Charlson Comorbidity Index on Mortality following Acute Pulmonary Embolism

Objectives: It was the aim of this study to determine the prognostic significance of the Charlson Comorbidity Index (CCI) following acute pulmonary embolism (PE) and assess the prognosis of patients without comorbidities (defined as a CCI score of 0). Methods: Outcomes of 1,023 consecutive patients admitted with confirmed PE were tracked after a median of 3.7 years (25-75th interquartile range 1.5-6.1 years). All were assigned a non-age-adjusted CCI score. Results: The median CCI score was 1.0 (interquartile range 0.0-3.0). Three hundred and fifty-one (34%) patients had a CCI score of 0. Only 1 (0.3%) of 31 in-hospital deaths occurred in patients with a CCI score of 0. Long-term mortality for these patients was similar to the population-derived age- and sex-matched mortality rate, and was significantly better than for those with a CCI score ≥1 (12.5 vs. 47.5%; p < 0.0001 adjusted for age and sex). In multivariate analysis, CCI (per 1-score increase) independently predicted in-hospital (hazard ratio 1.27, 95% confidence interval 1.09-1.49; p = 0.003) and post-discharge (hazard ratio 1.35, 95% confidence interval 1.29-1.42; p < 0.0001) death. The c statistics for the multivariate prediction models for in-hospital (incorporating CCI score and serum sodium level) and post-discharge death (age, CCI score, hyperlipidemia, serum sodium and hemoglobin) were 0.738 and 0.788, respectively (both p < 0.0001). Conclusion: The CCI can be incorporated into risk models, with good discriminatory power, for predicting in-hospital and long-term outcomes following acute PE. Patients with a CCI score of 0 have a favorable long-term outcome following acute PE.

Platelet activation in acute pulmonary embolism

Summary.  Background: Platelet activation is implicated in thrombotic disorders, but has not been described in acute clinical pulmonary embolism (PE). Objectives: To investigate the natural history of platelet activation in PE and associated markers of inflammation, thrombosis and cardiac dysfunction. Methods: Thirty‐five consecutive patients (age 62 ±17 years) with acute PE were prospectively enrolled and followed for 6 months. Platelet activation was assessed by flow cytometry [measuring expression of platelet P‐selectin, conformational activation of glycoprotein IIb/IIIa complex (PAC‐1) and formation of platelet–leukocyte complexes] and by plasma soluble P‐selectin. Platelet activation, right ventricular (RV) function (assessed as RV ejection area by transthoracic echocardiography), D‐dimer and high‐sensitivity C‐reactive protein (hs‐CRP) were measured at presentation and repeated over 6 months follow‐up. Results: Soluble P‐selectin (56 ±19 ng mL−1, anovaP < 0.0001) and PAC‐1 (1.5 ± 1.8%, anovaP = 0.005) were mildly but significantly increased in patients with acute PE relative to healthy young men (soluble P‐selectin 33 ± 13 ng mL−1, P < 0.001; PAC‐1 binding 0.5 ± 0.6%, P < 0.01) and age‐matched controls (soluble P‐selectin 31 ± 9 ng mL−1, P < 0.001; PAC‐1 binding 0.4 ±0.4%, P < 0.05). Platelet P‐selectin expression and platelet–leukocyte complexes were not increased during acute PE. Echocardiographic RV ejection area correlated inversely with soluble P‐selectin (r = −0.47, P = 0.007) and positively with platelet P‐selectin (r = 0.49, P = 0.0007), suggesting P‐selectin is shed from activated platelets in proportion to the severity of RV dysfunction. Elevated soluble P‐selectin, D‐dimer and hs‐CRP demonstrated a time‐dependent return to normal during 6 months follow‐up. Conclusion: Platelet activation is evident after acute PE. Platelet activation correlates with the severity of RV dysfunction, and can persist for several months after acute PE.

Right atrial to left atrial area ratio on early echocardiography predicts long-term survival after acute pulmonary embolism.

BackgroundCurrent guidelines recommend that transthoracic echocardiography (TTE) should be performed for acute risk stratification following acute pulmonary embolism (PE), but it is unclear whether the initial TTE can predict long-term outcome beyond six months. We sought to assess the potential of the initial right atrial (RA) to left atrial (LA) area ratio (RA/LA ratio) on TTE to predict long-term mortality in survivors of submassive PE.MethodsA derivation cohort comprised a previously reported group of 35 consecutive patients with acute PE who were intensively studied by serial TTE at 1, 2, 5 days, 2, 6, 12 and 26 weeks and RA/LA ratio related to long-term outcome. The Day 1 RA/LA ratio findings were then further related to long-term outcome in 158 patients followed for 3.6 ± 2.3 years.ResultsIn the derivation cohort, total mortality was 28.6% (n = 10) following a mean (±standard deviation) follow-up of 4.3 ± 1.9 years. The RA/LA ratio was highly dynamic, being increased at day 1, but normalised rapidly within 2–5 days of presentation and this was most marked amongst long-term non-survivors. A RA/LA ratio > 1.0 on day 1 was independently associated with a three-fold increase in long-term mortality on Kaplan-Meier analysis. Pooled analysis of 158 patient indicated that age, Charlson Comorbidity Index (CCI), simplified Pulmonary Embolism Severity Score (PESI), troponin T, day 1 RA/LA Ratio and pulmonary arterial systolic pressure (PASP) were univariate predictors of long-term mortality. Multivariate analysis identified Day 1 RA/LA Ratio (HR 1.7 per 10% increase,p = 0.002), CCI (HR 2.2 per 1 unit increase, p = 0.004) and age (HR 1.1, p = 0.03) as the only independent predictors of long-term mortality.ConclusionA RA/LA Ratio >1.0 at presentation with acute PE was associated with a three-fold increased risk of long-term mortality. The RA/LA ratio on presentation with an acute PE is a simple, novel predictor of long-term survival.

Cardiac troponin-T and the prediction of acute and long-term mortality after acute pulmonary embolism

BACKGROUND Although cardiac troponin elevation during acute pulmonary embolism (PE) predicts in-hospital death, its long-term prognostic significance, and the role of troponin-T concentration in this prediction, is unknown. Moreover, its use in acute PE in elderly populations with multiple comorbidities is not well described. METHODS Consecutive patients presenting with confirmed PE to a tertiary hospital between 2000 and 2007 with troponin-T measured were identified retrospectively and their outcomes tracked from a state-wide death registry. RESULTS There were 577 patients, (47% male) with a mean age (± standard deviation) of 70.1 ± 15.2 years, of whom 19 died during index admission. Of the 558 patients who survived to discharge, 186 patients died during a mean follow-up of 3.8 ± 2.4 years. There were 187 (32%) patients with elevated troponin-T (≥ 0.01 μg/L). Troponin-T concentration was significantly and independently associated with in-hospital and long-term mortality whether analyzed as a continuous or categorical variable (p<0.001). However, different cut-points were required to optimally predict in-hospital and post-discharge long-term mortality in multivariate analysis. Troponin-T ≥ 0.01 μg/L was not an independent predictor of in-hospital or post-discharge survival. A cut-point of troponin-T ≥ 0.03 μg/L was required to independently predict in-hospital death (p=0.03), and troponin-T ≥ 0.1 μg/L was required to independently predict long-term mortality (hazard ratio 2.3, 95% confidence interval 1.4-3.8, p=0.001). CONCLUSIONS Troponin-T elevation during acute PE shows a concentration-dependent relationship with acute and long-term outcome. Concentrations of troponin-T well above the threshold for detection may be required to independently contribute to prediction of outcome in elderly populations with acute PE.

Asymptomatic left ventricular dysfunction with long-term clozapine treatment for schizophrenia: a multicentre cross-sectional cohort study

Objectives Patients with schizophrenia treated with clozapine are at risk of acute myocarditis and dilated cardiomyopathy. However, there are no data on the prevalence of subclinical cardiomyopathy or its associations. Methods 100 consecutive patients with schizophrenia treated with clozapine for >1 year and without a history of cardiac pathology (group 1), 21 controls with a history of schizophrenia treated with non-clozapine antipsychotics for >1 year (group 2) and 20 controls without schizophrenia (group 3) were studied. Comprehensive evaluation by clinical examination, ECG, transthoracic echocardiography including left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS) and biochemical profiles were performed. Results Patients with schizophrenia were of similar age, but had higher body mass index (BMI), rates of smoking and hyperlipidaemia than controls. Patients with schizophrenia had received clozapine or non-clozapine antipsychotics for a mean duration of 6.8±5.3 and 9.7±6.1 years, respectively. Patients taking clozapine demonstrated globally impaired LVEF (58.3%: group 1 vs 62.2%: group 2 vs 64.8%: group 3, p<0.001) and GLS (−16.7%: group 1 vs −18.6%: group 2 vs −20.2%: group 3, p<0.001). Moreover, LVEF was <50% in 9/100 (9%) patients receiving clozapine and in non-clozapine schizophrenia patients or healthy controls, but this was not statistically significantly different (analysis of covariance, p=0.19). Univariate analysis in patients taking clozapine found that impaired LV was not predicted by high-sensitivity troponin T, but was associated with features of the metabolic syndrome (including increased triglycerides, low high-density lipoprotein cholesterol (HDL-C), high-sensitivity C reactive protein and BMI), elevated neutrophil count, elevated heart rate, smoking and N-terminal probrain natriuretic peptide. In patients taking clozapine, multivariable analysis identified elevated neutrophil count and low HDL-C as the only independent predictors of impaired GLS. Conclusions Asymptomatic mild LV impairment is common in patients with schizophrenia receiving long-term clozapine treatment and is associated with neutrophilia and low HDL-C.

Subacute cardiac toxicity following autologous haematopoietic stem cell transplantation in patients with normal cardiac function

Objective: To investigate subacute cardiac toxicity in patients with normal baseline cardiac function following autologous haematopoietic stem cell transplantation. Design: Prospective observational study. Patient and methods: Thirty-two consecutive patients (mean (SD) age 60 (11) years) with normal left ventricular ejection fraction (LVEF ⩾50%) undergoing autologous haematopoietic stem cell transplantation were studied. Transthoracic echocardiography (including colour tissue Doppler imaging-derived myocardial velocities, strain and strain rates), troponin-T and B-type natriuretic peptide (BNP) and clinical details were recorded at baseline, after conditioning chemotherapy and serially over 6 weeks from the day of transplantation. Results: The mean (SD) LVEF at baseline was 62 (6)% and decreased to 55 (16)%, 6 weeks after transplantation (p = 0.007). Cardiac toxicity (⩾10% absolute decline of LVEF to an LVEF ⩽50%) developed in 10 (31%) patients within 17 (8) days of transplantation and was usually reversible. In these 10 patients, the nadir LVEF was 39 (12)%. Two patients developed severe clinical pulmonary oedema, one episode of which was fatal. Troponin-T was mildly raised in only three of the patients with cardiac toxicity. Peak BNP values were similar in patients with or without post-transplant cardiac toxicity (149 (100) vs 196 (178) pg/ml, p = 0.43). Multivariate Cox proportional hazard regression identified baseline mitral annular systolic velocity as the only independent predictor of cardiac toxicity (hazard ratio 0.42, 95% confidence interval 0.20 to 0.86, p = 0.02). Conclusion: Subacute cardiac toxicity is common after autologous haematopoietic stem cell transplantation, even in patients with apparently normal left ventricular function. Anticipation of the period of greatest risk and recognition of patients with subclinical myocardial dysfunction may prevent clinical heart failure.

Unusual Features of Apical Hypertrophic Cardiomyopathy

Apical hypertrophic cardiomyopathy (HC) is commonly regarded as a relatively benign condition of young to middle-aged Japanese men. Apical HC in a predominantly Caucasian population is not well characterized. The cardiovascular characteristics, morbidity, and mortality of a series of elderly, predominantly Caucasian subjects with apical HC are described. Thirty-two consecutive patients with apical HC (mean age 71 years, 15 men) were identified from a teaching hospital without a specialized HC clinic. Twenty-three subjects were Caucasian, 8 were Asian, and none Japanese. Twenty-two patients had coexistent hypertension. Six patients had documented late evolution of apical HC on electrocardiography and echocardiography up to 5 years after previous documented normal left ventricular morphology on echocardiography. The diagnosis of apical HC was initially missed in 7 patients because of inadequate image quality of the left ventricular apex and a lack of awareness of the condition. The correct diagnosis was assigned to all 7 patients after repeat echocardiography. Six of 13 patients who underwent coronary angiography had associated coronary artery fistulae. One patient required an implantable defibrillator for exertional syncope. Ten of the patients developed atrial fibrillation, 6 of whom had complicating thromboembolic events. Of the 6 deaths in the cohort, 2 followed atrial fibrillation-related hemiplegic strokes, and 2 followed progressive heart failure. In conclusion, apical HC in a teaching hospital without a specialized HC clinic and in a predominantly Caucasian population is a disease of the elderly. Documented late morphologic evolution is not uncommon, with a high incidence of coronary fistulae and morbid atrial fibrillation.