J. Somaratne

The prognostic significance of heart failure with preserved left ventricular ejection fraction: a literature-based meta-analysis.

Heart failure (HF) with normal or preserved left ventricular (LV) ejection fraction (HFPEF) has been reported to be associated with similar outcome as HF with reduced EF (HFREF) in registry‐based and epidemiological analyses, but many of these studies excluded patients who did not have EF measurements. Conversely, prior prospective studies have reported better outcome for patients with HFPEF. We performed a meta‐analysis of prospective observational studies comparing all‐cause mortality in patients with HFREF and HFPEF.

Differences in Myocardial Structure and Coronary Microvasculature Between Men and Women With Coronary Artery Disease

Women younger than 75 years with stable angina or acute coronary syndrome have higher cardiac mortality than similarly aged men, despite less obstructive coronary artery disease. To determine whether the myocardial structure and coronary microvasculature of women differs from that of men, we performed histological analysis of biopsies from nonischemic left ventricular myocardium from 46 men and 11 women undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation, or furosemide therapy. The 2 patient groups had similar clinical characteristics, apart from a lower body surface area (BSA) in women (P=0.0015). Women had less interstitial fibrosis than men (P=0.019) but similar perivascular fibrosis. Arteriolar wall area/circumference ratio, a measure of arteriolar wall thickness, was 47% greater in women than men (P=0.012). Cardiomyocyte width and diffusion radius were positively correlated, and capillary length density was negatively correlated with BSA (P<0.05). Whereas cardiomyocyte width, capillary length density, diffusion radius, and cardiomyocyte width/BSA ratio were similar for men and women, women had a greater diffusion radius/BSA ratio (P=0.0038) and a greater diffusion radius/cardiomyocyte width ratio (P=0.027). Women also had lower vascular endothelial growth factor (VEGF) receptor-1 levels (P=0.048) and VEGF receptor-1/VEGF-A ratio (P=0.024) in plasma. We conclude that women with extensive coronary artery disease have greater arteriolar wall thickness and diffusion radius relative to BSA and to cardiomyocyte width than men, which may predispose to myocardial ischemia. Additional studies of larger numbers of women with less extensive coronary artery disease are required to confirm these findings.

Screening for left ventricular hypertrophy in patients with type 2 diabetes mellitus in the community

BackgroundLeft ventricular hypertrophy (LVH) is a strong predictor of cardiovascular disease and is common among patients with type 2 diabetes. However, no systematic screening for LVH is currently recommended for patients with type 2 diabetes. The purpose of this study was to determine whether NT-proBNP was superior to 12-lead electrocardiography (ECG) for detection of LVH in patients with type 2 diabetes.MethodsProspective cross-sectional study comparing diagnostic accuracy of ECG and NT-proBNP for the detection of LVH among patients with type 2 diabetes. Inclusion criteria included having been diagnosed for > 5 years and/or on treatment for type 2 diabetes; patients with Stage 3/4 chronic kidney disease and known cardiovascular disease were excluded. ECG LVH was defined as either the Sokolow-Lyon or Cornell voltage criteria. NT-proBNP level was measured using the Roche Diagnostics Elecsys assay. Left ventricular mass was assessed from echocardiography. Receiver operating characteristic curve analysis was carried out and area under the curve (AUC) was calculated.Results294 patients with type 2 diabetes were recruited, mean age 58 (SD 11) years, BP 134/81 ± 18/11 mmHg, HbA1c 7.3 ± 1.5%. LVH was present in 164 patients (56%). In a logistic regression model age, gender, BMI and a history of hypertension were important determinants of LVH (p < 0.05). Only 5 patients with LVH were detected by either ECG voltage criteria. The AUC for NT-proBNP in detecting LVH was 0.68.ConclusionsLVH was highly prevalent in asymptomatic patients with type 2 diabetes. ECG was an inadequate test to identify LVH and while NT-proBNP was superior to ECG it remained unsuitable for detecting LVH. Thus, there remains a need for a screening tool to detect LVH in primary care patients with type 2 diabetes to enhance risk stratification and management.

Atrial fibrillation and the risk of death in patients with heart failure: a literature-based meta-analysis.

Background: Heart failure (HF) and atrial fibrillation (AF) are common, associated with significant morbidity and mortality, and frequently coexist. It is uncertain from published data if the presence of AF in patients with HF is associated with an incremental adverse outcome. The aim of this study was to combine the results of all studies investigating prognosis for patients with HF and AF compared with those in sinus rhythm (SR) to asses the mortality risk associated with this arrhythmia.

Diastolic Dysfunction of Aging Is Independent of Myocardial Structure but Associated with Plasma Advanced Glycation End-Product Levels

Background Heart failure is associated with abnormalities of myocardial structure, and plasma levels of the advanced glycation end-product (AGE) Nε-(carboxymethyl)lysine (CML) correlate with the severity and prognosis of heart failure. Aging is associated with diastolic dysfunction and increased risk of heart failure, and we investigated the hypothesis that diastolic dysfunction of aging humans is associated with altered myocardial structure and plasma AGE levels. Methods We performed histological analysis of non-ischemic left ventricular myocardial biopsies and measured plasma levels of the AGEs CML and low molecular weight fluorophores (LMWFs) in 26 men undergoing coronary artery bypass graft surgery who had transthoracic echocardiography before surgery. None had previous cardiac surgery, myocardial infarction, atrial fibrillation, or heart failure. Results The patients were aged 43–78 years and increasing age was associated with echocardiographic indices of diastolic dysfunction, with higher mitral Doppler flow velocity A wave (r = 0.50, P = 0.02), lower mitral E/A wave ratio (r = 0.64, P = 0.001), longer mitral valve deceleration time (r = 0.42, P = 0.03) and lower early diastolic peak velocity of the mitral septal annulus, e’ (r = 0.55, P = 0.008). However, neither mitral E/A ratio nor mitral septal e’ was correlated with myocardial total, interstitial or perivascular fibrosis (picrosirius red), immunostaining for collagens I and III, CML, and receptor for AGEs (RAGE), cardiomyocyte width, capillary length density, diffusion radius or arteriolar dimensions. Plasma AGE levels were not associated with age. However, plasma CML levels were associated with E/A ratio (r = 0.44, P = 0.04) and e’ (r = 0.51, P = 0.02) and LMWF levels were associated with E/A ratio (r = 0.49, P = 0.02). Moreover, the mitral E/A ratio remained correlated with plasma LMWF levels in all patients (P = 0.04) and the mitral septal e’ remained correlated with plasma CML levels in non-diabetic patients (P = 0.007) when age was a covariate. Conclusions Diastolic dysfunction of aging was independent of myocardial structure but was associated with plasma AGE levels.

When Collateral Supply is Accounted For Epicardial Stenosis Does Not Increase Microvascular Resistance

Background— The relationship between epicardial stenosis and microvascular resistance remains controversial. Exploring the relationship is critical, as many tools used in interventional cardiology imply minimal and constant resistance. However, variable collateralization may impact well on these measures. We hypothesized that when collateral supply was accounted for, microvascular resistance would be independent of epicardial stenosis. Methods and Results— Forty patients with stable angina were studied before and following percutaneous intervention. A temperature and pressure sensing guide wire was used to derive microvascular resistance using the index of microcirculatory resistance (IMR), defined as the hyperemic distal pressure multiplied by the hyperemic mean transit time. Lesion severity was assessed using fractional flow reserve. For comparison, evaluation of an angiographically normal reference vessel from the same subject also was undertaken. Both simple IMR (sIMR) and IMR corrected for collateral flow (cIMR) were calculated. When collateral supply was not accounted for, there was a significant difference in IMR values between the culprit, the post PCI, and nonculprit values (culprit sIMR 26.68±2.06, nonculprit sIMR 18.37±1.89, P=0.002; post percutaneous intervention sIMR 18.5±1.94 versus culprit sIMR 26.68±2.06, P<0.0001). However, when collateral supply was accounted for there was no difference observed (cIMR 16.96±1.78 versus nonculprit sIMR 18.37±1.89, P=0.52; post percutaneous intervention sIMR 18.5±1.94 versus cIMR 16.96±1.78, P=0.42). Conclusions— When collateral supply is accounted for, epicardial stenosis does not increase microvascular resistance in patients with stable angina.

Pseudonormal mitral filling is associated with similarly poor prognosis as restrictive filling in patients with heart failure and coronary heart disease: a systematic review and meta-analysis of prospective studies.

OBJECTIVE The study objective was to more precisely evaluate the link between the pseudonormal mitral filling pattern and death by way of systematic review and meta-analysis. METHODS Patients with heart failure (HF) and coronary artery disease (CAD) were included. Online databases were searched for prospective studies of patients with HF and CAD who had comprehensive echocardiography. Mortality in patients with pseudonormal filling was compared with restrictive filling and other nonrestrictive filling patterns, including normal and abnormal relaxation. Review Manager Version 4.2.7 software was used for the analysis. RESULTS Seven studies (5 HF and 2 CAD) were identified, and 887 patients (244 deaths) were included. The pseudonormal filling pattern conferred a 4-fold increase in odds of death compared with abnormal relaxation/normal (odds ratio 4.46; 95% confidence interval, 2.87-6.92). Outcome was similar when restrictive filling was compared with pseudonormal filling (odds ratio 1.16; 95% confidence interval, 0.78-1.74). Death was the main outcome measure. CONCLUSION This literature-based meta-analysis, pooling results from 7 prospective studies, demonstrates the 4-fold increase in odds of death associated with pseudonormal filling compared with abnormal relaxation/normal. The pseudonormal filling pattern and restrictive filling pattern are associated with similar risk of death. These data further support the need for a comprehensive assessment of diastolic filling, including assessment for pseudonormal filling, as part of routine echocardiographic risk stratification in patients with HF and CAD.

Neurological and systemic complications of tuberculous meningitis and its treatment at Auckland City Hospital, New Zealand

Mortality and serious long-term sequelae still occur in about 50% of patients with tuberculous meningitis. The frequency and the clinical features of neurological and systemic complications were determined in a retrospective review of 104 patients with tuberculous meningitis. Complications occurred in 81 patients (78%). The most common complications were: hyponatraemia 49%, hydrocephalus 42%, stroke 33%, cranial nerve palsies 29%, epileptic seizures 28%, diabetes insipidus 6%, tuberculoma 3%, myeloradiculopathy 3% and hypothalamic syndrome 3%. The most common iatrogenic complication was hepatotoxicity related to anti-tuberculosis treatment in seven patients. Twenty-three patients (22%) died. At last follow-up one patient (1%) remained in a persistent vegetative state, 14 patients (13%) had severe disability and 12 patients (12%) were moderately disabled. The most common complications in the 81 long-term survivors were cognitive impairment (12%) and epilepsy (11%). Neurological and systemic complications of tuberculous meningitis were common and were important causes of mortality and long-term morbidity.

Obesity Is Associated with Lower Coronary Microvascular Density

Background Obesity is associated with diastolic dysfunction, lower maximal myocardial blood flow, impaired myocardial metabolism and increased risk of heart failure. We examined the association between obesity, left ventricular filling pressure and myocardial structure. Methods We performed histological analysis of non-ischemic myocardium from 57 patients (46 men and 11 women) undergoing coronary artery bypass graft surgery who did not have previous cardiac surgery, myocardial infarction, heart failure, atrial fibrillation or loop diuretic therapy. Results Non-obese (body mass index, BMI, ≤30 kg/m2, n=33) and obese patients (BMI >30 kg/m2, n=24) did not differ with respect to myocardial total, interstitial or perivascular fibrosis, arteriolar dimensions, or cardiomyocyte width. Obese patients had lower capillary length density (1145±239, mean±SD, vs. 1371±333 mm/mm3, P=0.007) and higher diffusion radius (16.9±1.5 vs. 15.6±2.0 μm, P=0.012), in comparison with non-obese patients. However, the diffusion radius/cardiomyocyte width ratio of obese patients (0.73±0.11 μm/μm) was not significantly different from that of non-obese patients (0.71±0.11 μm/μm), suggesting that differences in cardiomyocyte width explained in part the differences in capillary length density and diffusion radius between non-obese and obese patients. Increased BMI was associated with increased pulmonary capillary wedge pressure (PCWP, P<0.0001), and lower capillary length density was associated with both increased BMI (P=0.043) and increased PCWP (P=0.016). Conclusions Obesity and its accompanying increase in left ventricular filling pressure were associated with lower coronary microvascular density, which may contribute to the lower maximal myocardial blood flow, impaired myocardial metabolism, diastolic dysfunction and higher risk of heart failure in obese individuals.

Impact of right atrial pressure on decision-making using fractional flow reserve (FFR) in elective percutaneous intervention

BACKGROUND We undertook a prospective study to assess the impact of routine incorporation of right atrial pressure into the calculation of FFR in a real world elective PCI cohort. METHODS 42 patients with stenoses in 2 separate epicardial vessels at coronary angiography were studied. Using a temperature and pressure sensing guidewire (TPSG) FFR and FFRRAP were performed in the target vessel pre and post PCI and in a non-target vessel. FFR was defined as Pd/Pa, FFRRAP as Pd-Pv/Pa-Pv where Pv was right atrial pressure and Pd/Pa were the hyperemic distal and proximal arterial pressures respectively. RESULTS Mean RAP was 9.1 ± 0.7 mmHg. Mean FFR was significantly lower when RAP was included in the calculation (FFRRAP 0.77 ± 0.19 vs. FFR 0.80 ± 0.16, p<0.001). In the target vessel pre PCI, incorporating RAP into the calculation of FFR resulted in a significant difference in the FFR value (FFR Pre-PCI 0.69 ± 0.02 vs. FFRRAP Pre-PCI 0.63 ± 0.03, p<0.0001). 21 patients had an FFR ≤ 0.8 in the group. If right atrial pressure were utilized to calculate FFR prior to PCI, an additional 9 patients would have been re-categorised to an FFR ≤ 0.8. Following PCI, mean FFR was lower when RAP was incorporated (Post PCI FFRRAP 0.93±0.05 vs. Post PCI FFR 0.95 ± 0.06, p<0.001). CONCLUSION Incorporation of right atrial pressure into the calculation of FFR significantly alters FFR values and may potentially reclassify lesions below ischaemic thresholds.