A. Ng

Three-dimensional and two-dimensional quantitative coronary angiography, and their prediction of reduced fractional flow reserve

AIMS We investigated whether three-dimensional (3D) and two-dimensional quantitative coronary angiography (2D-QCA) measurements differed in their accuracy in predicting reduced fractional flow reserve (FFR), and how this varied with stenosis severity and the FFR cut-off used. METHODS AND RESULTS Three-dimensional and 2D-QCA were compared in their measurements of minimum luminal area (MLA), percentage area stenosis, lesion length, minimum luminal diameter (MLD) and percentage diameter stenosis, and in their prediction of functionally significant FFR. In total, 63 target lesions were interrogated in 63 patients undergoing elective percutaneous coronary intervention. Of all measurements of lesion severity obtained by 3D-QCA, MLA best correlated with FFR (R = 0.63, P < 0.001), and was the most accurate predictor of FFR < 0.75 (C statistic 0.86, P < 0.001). Of 2D-QCA measurements, MLD correlated best with FFR (R = 0.58, P < 0.001), and best predicted FFR < 0.75 (C statistic 0.80, P < 0.001). Overall, 3D-QCA showed a non-significant trend towards more accurate prediction of FFR than 2D-QCA, especially in intermediate lesions. The relationship between FFR and apparent stenosis severity was found to be curvilinear. Both 3D- and 2D-QCA were less accurate in intermediate lesions, and in predicting FFR ≤ 0.80 than in predicting FFR <0.75. CONCLUSIONS The accuracy of QCA in predicting functionally significant FFR is limited and is dependent on FFR cut-off used and lesion severity. Where FFR is not available or contraindicated, 3D-QCA may assist in the evaluation of coronary lesions of intermediate severity.

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.

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.

Left Atrial Compression and the Mechanism of Exercise Impairment in Patients With a Large Hiatal Hernia

OBJECTIVES The purpose of this study was to determine the association between cardiac compression and exercise impairment in patients with a large hiatal hernia (HH). BACKGROUND Dyspnea and exercise impairment are common symptoms of a large HH with unknown pathophysiology. Studies evaluating the contribution of cardiac compression to the pathogenesis of these symptoms have not been performed. METHODS We collected clinical data from a consecutive series of 30 patients prospectively evaluated with resting and stress echocardiography, cardiac computed tomography, and respiratory function testing before and after laparoscopic HH repair. Left atrial (LA), inferior pulmonary vein, and coronary sinus compression was analyzed in relation to exercise capacity (metabolic equivalents [METs] achieved on Bruce treadmill protocol). RESULTS Exertional dyspnea was present in 25 of 30 patients (83%) despite normal mean baseline respiratory function. Moderate to severe LA compression was qualitatively present in 23 of 30 patients (77%) on computed tomography. Right and left inferior pulmonary vein and coronary sinus compression was present in 11 of 30 (37%), 12 of 30 (40%), and 26 of 30 (87%) patients, respectively. Post-operatively, New York Heart Association functional class and exercise capacity improved significantly (number of patients in New York Heart Association functional classes I, II, III, and IV: 6, 11, 11, and 2 vs. 26, 4, 0, and 0, respectively, p < 0.001; METs [percentage predicted]: 75 ± 24% vs. 112 ± 23%, p < 0.001) and resolution of cardiac compression was observed. Absolute change in LA diameter on the echocardiogram was the only independent cardiorespiratory predictor of exercise capacity improvement post-operatively (p = 0.006). CONCLUSIONS We demonstrate, for the first time, marked exercise impairment and cardiac compression in patients with a large HH and normal respiratory function. After HH repair, exercise capacity improves significantly and correlates with resolution of LA compression.

Flow recirculation zone length and shear rate are differentially affected by stenosis severity in human coronary arteries

Flow recirculation zones and shear rate are associated with distinct pathogenic biological pathways relevant to thrombosis and atherogenesis. The interaction between stenosis severity and lesion eccentricity in determining the length of flow recirculation zones and peak shear rate in human coronary arteries in vivo is unclear. Computational fluid dynamic simulations were performed under resting and hyperemic conditions on computer-generated models and three-dimensional (3-D) reconstructions of coronary arteriograms of 25 patients. Boundary conditions for 3-D reconstructions simulations were obtained by direct measurements using a pressure-temperature sensor guidewire. In the computer-generated models, stenosis severity and lesion eccentricity were strongly associated with recirculation zone length and maximum shear rate. In the 3-D reconstructions, eccentricity increased recirculation zone length and shear rate when lesions of the same stenosis severity were compared. However, across the whole population of coronary lesions, eccentricity did not correlate with recirculation zone length or shear rate (P = not signficant for both), whereas stenosis severity correlated strongly with both parameters (r = 0.97, P < 0.001, and r = 0.96, P < 0.001, respectively). Nonlinear regression analyses demonstrated that the relationship between stenosis severity and peak shear was exponential, whereas the relationship between stenosis severity and recirculation zone length was sigmoidal, with an apparent threshold effect, demonstrating a steep increase in recirculation zone length between 40% and 60% diameter stenosis. Increasing stenosis severity and lesion eccentricity can both increase flow recirculation and shear rate in human coronary arteries. Flow recirculation is much more sensitive to mild changes in the severity of intermediate stenoses than is peak shear.

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.

Acute coronary syndrome and stable coronary artery disease: Are they so different? Long-term outcomes in a contemporary PCI cohort

BACKGROUND Patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndromes (ACS) are known to have poorer short-term prognosis compared to stable coronary artery (CAD) patients undergoing elective PCI. Few studies have made direct comparison of long-term mortality between ACS and stable CAD patients undergoing PCI. The aim of our study was to compare the long-term mortality following PCI between patients with ACS and those with stable CAD. METHODS We examined consecutive patients undergoing PCI with stenting at a tertiary referral hospital. Clinical, angiographic and biochemical data were collected and analysed. The primary outcome was all-cause mortality retrieved from the Statewide Death Registry database. RESULTS Included were 1923 consecutive PCI patients (970 stable CAD and 953 ACS). The mean follow-up time was 4.1 years ± 1.8 years. In-hospital mortality was 1.4% overall, seen exclusively in patients with ACS (n=28, 2.9%). Post-discharge mortality was 6.7% among patients with stable CAD and 10.5% for ACS (P<0.01). Multivariate predictors of post-discharge deaths for both groups included age (HR 1.08 per year, P<0.001) and impaired renal function (HR 2.49, P<0.001). Following adjustment for these factors, an ACS indication for PCI was not associated with greater post-discharge mortality (adjusted HR 1.18: 0.85-1.64, P=0.32). CONCLUSIONS Patients undergoing PCI following an ACS have higher long-term mortality to those with stable CAD, which is potentially explained by a greater prevalence of comorbidities. This suggests that for the ACS population, contemporary interventional and medical management strategies may effectively and specifically counter the adverse prognostic impact of coronary instability and myocardial damage.

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.

Sleep disordered breathing in chronic heart failure

Heart failure is a growing problem, placing an increasing burden on public health resources and continuing to exert a high toll in mortality and morbidity. Sleep disordered breathing (SDB) is also a major public health problem and is associated with an increased risk of fatal and non-fatal cardiovascular events. Current evidence suggests SDB, particularly central SDB, is more prevalent in patients with chronic heart failure (CHF) than in the general population, but is under-diagnosed as SDB symptoms are less prevalent in CHF. This is further hampered by the absence of a simple and accurate screening tool and limited access to sleep facilities to diagnose SDB in the large numbers of patients with CHF. The presence of SDB in patients with CHF imposes increased haemodynamic burdens and results in autonomic abnormalities. Central SDB is an independent marker of worse prognosis, and evidence is increasing that obstructive SDB is also associated with higher mortality in patients with CHF. Optimal treatment of central SDB in these patients remains uncertain. While evidence of efficacy of positive pressure ventilation is stronger in obstructive SDB, improvement in survival for patients with both CHF and SDB awaits definitive trials. This paper summarizes our current understanding of the pathophysiology of SDB in CHF, and the cardiovascular consequences, and reviews the evidence for the beneficial effects of treatment of SDB in patients with CHF.

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.