Prosthetic Valve Infective Endocarditis With Mycobacterium Fortuitum: Antibiotics Alone Can Be Curative.

Rapidly growing non-tuberculous mycobacteria (RGM) are a rare, often fatal cause of infective endocarditis. Although surgery has been the cornerstone of RGM endocarditis therapy, we present the first documented adult case of Mycobacterium fortuitum endocarditis cured with antibiotic therapy.

Persistent global hypercoagulability in long-term survivors of acute pulmonary embolism.

Hypercoagulable and/or hypofibrinolytic states are risk factors for venous thromboembolism (VTE) including acute pulmonary embolism. Current screening for thrombophilia is targeted towards identifying a specific defect and guidelines recommend a population-based rather than individualized strategy for anticoagulation treatment. We investigated whether there is a global hypercoagulable state in long-term survivors of pulmonary embolism no longer receiving therapeutic anticoagulation utilizing the overall haemostatic potential (OHP) assay, which assesses overall coagulation potential (OCP), OHP and overall fibrinolytic potential (OFP). Long-term survivors of acute pulmonary embolism were identified from a local registry and OHP assays were performed and compared with age and sex-matched controls without pulmonary embolism. Time courses of fibrin formation and degradation were measured by spectrophotometry (absorption 405 nm) after addition of tissue factor and tissue plasminogen activator to plasma. OHP assays were performed in 67 long-term survivors of single pulmonary embolism (7.9 ±â€Š1.4 years after pulmonary embolism) and 20 age (61.7 ±â€Š11.2 vs 56.6 ±â€Š6.4 years, P = 0.06) and sex (P = 0.45)-matched controls. Survivors of pulmonary embolism were more hypercoagulable as reflected by significantly higher OCP (56.4 ±â€Š13.0 vs 49.9 ±â€Š6.9, P = 0.03) and had impaired fibrinolysis with higher OHP (12.6 ±â€Š7.0 vs 5.9 ±â€Š2.0, P < 0.001) and lower OFP (78.1 ±â€Š9.4 vs 88.2 ±â€Š2.9, P < 0.001) compared with controls. Importantly, these abnormalities in overall coagulation were independently predicted by levels of fibrinogen, platelet count, shortened activated partial thromboplastin time and inflammatory markers suggesting a multifactorial cause. Long-term survivors of pulmonary embolism demonstrate enhanced global coagulation and reduced fibrinolytic potential. Assessment of global coagulation may provide new insights into the aggregate effects of multiple prothombotic factors and long-term risk of VTE recurrence.

Impaired 6-min walk test, heart rate recovery and cardiac function post pulmonary embolism in long-term survivors.

BACKGROUND: The functional capacity of long-term survivors of submassive pulmonary embolism (PE) is unreported. A six-minute walk distance (6MWD) <350 m and reduced heart rate recovery (HRR) indicate adverse prognosis in various chronic diseases. METHODS: Long-term survivors of acute PE (January 2000-June 2005) were invited to undergo prospectively planned six-minute walk test (6MWT), transthoracic echocardiogram (TTE), clinical and biochemical evaluation with cardiac biomarkers. HRR was calculated as the difference between heart rate at 6-min during and at 1-min post 6MWT. RESULTS: 120 patients (52 males; mean age [±standard deviation] - 65 ± 14 years) were identified 7.7 ± 1.4 years after PE. 6MWD was significantly lower than that predicted after adjustment for age, sex, and height (448 ± 114 m vs 475 ± 89 m, p = 0.005), and 16% (17/104) had 6MWD <350 m. Among patients with no baseline comorbidities at follow-up (Charlson comorbidity index = 0), 8% (4/52) had 6MWD <350 m. Resting TTE identified 29% of patients had raised right ventricular (RV) pulmonary pressure (pulmonary arterial systolic pressure [PASP] >36 mmHg) and 13% had impaired RV function. Patients with 6MWD <85% predicted had significantly greater impairment of RV longitudinal function (p < 0.001), higher PASP (p < 0.001) and pulmonary vascular resistance (p < 0.001), elevated NT-proBNP (p = 0.03) and high-sensitivity troponin-T (HsTropT, p = 0.03), but similar left ventricular systolic and diastolic function, to those with normal 6MWT. CONCLUSIONS: Apparently well, long-term survivors of PE demonstrate impaired exercise capacity, heart rate recovery, mild pulmonary hypertension, raised PVR and right ventricular dysfunction associated with elevated NT-proBNP and HsTropT.

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

BACKGROUND: Current 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. METHODS: A 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. RESULTS: In 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. CONCLUSION: A 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.

Fluctuation of serum sodium and its impact on short and long-term mortality following acute pulmonary embolism.

BACKGROUND: Baseline hyponatremia predicts acute mortality following pulmonary embolism (PE). The natural history of serum sodium levels after PE and the relevance to acute and long-term mortality after the PE is unknown. METHODS: Clinical details of all patients (n = 1023) admitted to a tertiary institution from 2000-2007 with acute PE were retrieved retrospectively. Serum sodium results from days 1, 3-4, 5-6, and 7 of admission were pre-specified and recorded. We excluded 250 patients without day-1 sodium or had <1 subsequent sodium assessment, leaving 773 patients as the studied cohort. There were 605 patients with normonatremia (sodium≥135 mmol/L throughout admission), 57 with corrected hyponatremia (day-1 sodium<135 mmol/L, then normalized), 54 with acquired hyponatremia and 57 with persistent hyponatremia. Patients' outcomes were tracked from a state-wide death registry and analyses performed using multivariate-regression modelling. RESULTS: Mean (±standard deviation) day-1 sodium was 138.2±4.3 mmol/L. Total mortality (mean follow-up 3.6±2.5 years) was 38.8% (in-hospital mortality 3.2%). There was no survival difference between studied (n = 773) and excluded (n = 250) patients. Day-1 sodium (adjusted hazard ratio [aHR] 0.89, 95% confidence interval [CI] 0.83-0.95, p = 0.001) predicted in-hospital death. Relative to normonatremia, corrected hyponatremia increased the risk of in-hospital death 3.6-fold (95% CI 1.20-10.9, p = 0.02) and persistent hyponatremia increased the risk 5.6-fold (95% CI 2.08-15.0, p = 0.001). Patients with either persisting or acquired hyponatremia had worse long-term survival than those who had corrected hyponatremia or had been normonatremic throughout (aHR 1.47, 95% CI 1.06-2.03, p = 0.02). CONCLUSION: Sodium fluctuations after acute PE predict acute and long-term outcome. Factors mediating the correction of hyponatremia following acute PE warrant further investigation.

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.

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.

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.

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.

Intravascular blood sampling using the export catheter does not induce artifactual platelet activation.

We sought to investigate the feasibility of using the Export catheter to sample blood from the coronary arteries for studies of platelet activation. A pilot comparison between the Export catheter and the established Simmons catheter--currently used to sample blood from the coronary sinus--was performed. Triplicate blood samples were obtained from the descending aorta for each catheter in 10 patients, and analyzed for platelet P-selectin expression, PAC-1 expression, and platelet-leukocyte aggregate formation by flow cytometry. We found no significant increase in levels of platelet activation above that of reference values and no significant differences between the two catheters.

Natural history of right ventricular dysfunction after acute pulmonary embolism.

BACKGROUND: Acute pulmonary embolism (PE) associated with right ventricular (RV) dysfunction has an adverse prognosis. We investigated individual parameters of RV dysfunction after acute PE, assessing their correlation with the PE extent and recovery during 6 months. METHODS: In all, 35 patients (age 63 +/- 18 years) with acute PE were prospectively investigated for 6 months with serial echocardiography, incorporating longitudinal myocardial-velocity and strain imaging. The extent of PE was quantified on day 1 by ventilation/perfusion pulmonary scintigraphy with PE defined as large when there was greater than 30% lung involvement. RESULTS: PE extent correlated strongly with a number of parameters of RV function, and the strongest univariate correlates were tricuspid annular motion (TAM) (r = -0.65, P < .0001) and the ratio of RV apical to RV basal systolic velocity (r = 0.66, P < .0001). Multivariate analysis identified TAM (P < .0001) and RV basal late-diastolic velocity (P = .01) as independently predicting PE extent, with a combined correlation (R2 = 0.52, P < .0001). A TAM of less than 2.0 cm had sensitivity, specificity, and positive- and negative-predictive values of 75%, 84%, 75%, and 79%, respectively, in predicting large PE. Prospective follow-up identified that RV:left ventricular end-diastolic area ratio returned to normal within 6 weeks, whereas TAM and ratio of RV apical to RV basal systolic velocity normalized after 3 to 6 months. CONCLUSION: TAM and ratio of RV apical to RV basal systolic velocity are useful indicators of the extent of PE, and provide unique insights into the recovery of RV function after acute PE.

Influence of history of heart failure on diagnostic performance and utility of B-type natriuretic peptide testing for acute dyspnea in the emergency department.

BACKGROUND: The aim of this study was to assess the impact of a history of heart failure (HF) on emergency department (ED) B-type natriuretic peptide (BNP) testing and impact of feedback of BNP level to ED physicians. METHODS: Admission BNP was measured in 143 patients (mean age 79 +/- 10 years) presenting to the ED with dyspnea. Emergency department physicians scored probability of HF as cause of dyspnea and categorized cause of dyspnea. An independent cardiologist determined cause of dyspnea after chart review. In 83 patients, ED physicians rescored and reclassified patients after BNP measurement and evaluated test utility. RESULTS: The area under the receiver operating characteristic curve for BNP diagnosis of HF cause of dyspnea was significantly worse in patients with history of HF than those without (0.74 vs 0.94, P < .01) and in those with left ventricular ejection fraction <50% (0.64 vs 0.87, P < .05). A BNP cut point of 100 pg/mL had 100% sensitivity but only 41% specificity for diagnosing acute HF, whereas a cut point of 400 pg/mL had 87% sensitivity and 76% specificity. Emergency department physicians rated BNP useful in 64% of patients, and diagnostic uncertainty was reduced from 53% to 25% (P < .001). CONCLUSION: B-type natriuretic peptide test performance for diagnosis of dyspnea cause is significantly reduced in patients with a history of HF and must be taken into consideration in the evaluation of such patients in the ED.

Atrial and ventricular echocardiographic correlates of the extent of pulmonary embolism in the elderly.

BACKGROUND: Acute pulmonary thromboembolism (PTE) can be associated with right ventricular (RV) dysfunction. The relative importance of individual echocardiographic parameters, including those suggesting interdependence between right and left heart chambers, in predicting thromboembolic burden in elderly patients with acute PTE is unknown. METHODS: We retrospectively studied the transthoracic echocardiograms of 63 elderly patients (age 71 +/- 16 years) with acute PTE, and assessed which individual echocardiographic parameters identified more than 30% pulmonary artery obstruction on the basis of quantitative ventilation/perfusion pulmonary scintigraphy. RESULTS: RV hypokinesis (visual grade 0-3, P = .02), and the quantitative parameters RV end-systolic area (P = .005) and RV ejection area (P = .01) were associated with more extensive pulmonary artery obstruction. Although right atrial end-systolic area and RV end-diastolic area did not correlate with extent of PTE, the ratio of RV:left ventricular end-diastolic area (P = .003), and ratio of right:left atrial end-systolic area (P = .004), were strongly associated with the extent of pulmonary artery obstruction. These transthoracic echocardiographic parameters were independent of clinical variables such as prior chronic lung disease, congestive cardiac failure, or prior PTE. CONCLUSION: RV systolic dysfunction, RV end-systolic dilatation, right:left atrial end-systolic area ratio, and RV:left ventricular end-diastolic area ratio correlate with extent of PTE in the elderly.

Isolated noncompaction involving the left ventricular apex in adults.

We present a series of 9 adults in 2 families with isolated noncompaction of the ventricular myocardium involving the left ventricular apex. Three of these patients had been previously misdiagnosed as having dilated cardiomyopathy, apical hypertrophic cardiomyopathy, or apical mural thrombus. Phenotypic variation was observed with gradation of severity of noncompaction and left ventricular systolic dysfunction between first-degree relatives.