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P M Elliott

Publications and source records attributed to P M Elliott.

At least 19 recordsLinked to original sources
PubMed2006

Extracellular matrix turnover and disease severity in Anderson-Fabry disease.

BACKGROUND: Anderson-Fabry Disease (AFD) is an inherited metabolic disease associated with premature death secondary to cardiovascular and renal disease. Patients with AFD develop progressive left ventricular (LV) remodelling and heart failure. We hypothesized that altered extracellular matrix (ECM) turnover contributes to the pathophysiology of cardiac disease in AFD. METHODS AND RESULTS: Twenty-nine consecutive patients (44.1 +/- 11.7 years, 15 male) with AFD and 21 normal controls (39.7 +/- 11.3 years, 10 male) had serum analysed for matrix metalloproteinase-9 (MMP-9), and tissue inhibitor of matrix metalloproteinase-1 and -2 (TIMP-1, TIMP-2). All patients underwent clinical assessment, echocardiography and Mainz Severity Score Index (MSSI) measurement, a validated severity score in AFD. MMP-9 levels were significantly higher in patients than controls (1003.8 +/- 337.8 ng/ml vs 576.7 +/- 276.3 ng/ml respectively, p < 0.001). There were no differences in TIMP levels between patients and controls. There was a positive correlation between MMP-9 levels and MSSI (r = 0.5, p = 0.01). There was a negative correlation between MMP-9 and endocardial fractional shortening (FS) (r = -0.5, p = 0.01) and mid-wall FS (r = -0.6, p = 0.001). There was no correlation between other echocardiographic parameters and MMP-9 levels. These relations were independent of age and sex using stepwise linear regression analysis. CONCLUSIONS: Patients with AFD have abnormal ECM turnover compared to normal controls. The correlation between MMP-9 levels and systolic function suggests that altered ECM turnover is important in cardiac remodelling. The association between MMP-9 and overall disease severity suggests that circulating levels of MMP-9 may provide a useful marker for assessing the response of patients with AFD to enzyme replacement treatment.

Adult↗
PubMed2005

Historical trends in reported survival rates in patients with hypertrophic cardiomyopathy.

OBJECTIVE: To determine the range of survival rates of patients with hypertrophic cardiomyopathy (HCM) by comparing and contrasting the natural history of a cohort of patients seen between 1988 and 2002 with that of other published series. METHODS: 956 adult (> or = 16 years old) patients with HCM (572 men, mean (SD) age 42 (15) years, range 16-88) were evaluated by ECG, Holter, exercise testing, and echocardiography. Patient characteristics and survival data were compared with those in natural history studies from referral and non-referral centres published between 1960 and January 2003. RESULTS: The duration of follow up was 69 (45) months. 120 (12.6%) patients died or underwent cardiac transplantation. Sudden cardiac death (n = 48) was the most common mode of death. The annual rate of sudden death or implantable cardioverter-defibrillator discharge was 1.02 (95% confidence interval (CI) 0.76 to 1.26). Annual rates for heart failure death or transplantation and stroke related death were 0.55% (95% CI 0.37% to 0.78%) and 0.07% (95% CI 0.02% to 0.19%), respectively. When studies published within the last 10 years of the study period were compared with earlier reports, the size of individual study cohorts was larger (309 (240.6) v 136.5 (98.8), p = 0.058) and the proportion with severe functional limitation NYHA class III/IV lower (12.4% v 24.8%, p < 0.0001), and fewer patients underwent septal myotomy-myectomy (5.2% v 18.7%, p < 0.0001). Published sudden death rates over the last 10 years were lower than previously published figures (median 1.0% (range 0.1-1.7) v 2.0% (0-3.5)). CONCLUSION: Published survival rates in HCM cohorts have improved progressively over the past 40 years. In the modern era the prevalence of disease related complications is similar in all reporting centres.

Adolescent↗
PubMed2005

Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with alpha galactosidase A.

OBJECTIVE: To measure coronary flow reserve (CFR), an index of microvascular function, in Anderson-Fabry disease (AFD) at baseline and after enzyme replacement therapy (ERT). METHODS AND RESULTS: Mean (SD) myocardial blood flow (MBF) at rest and during hyperaemia (adenosine 140 microg/kg/min) was measured in 10 male, non-smoking patients (53.8 (10.9) years, cholesterol 5.5 (1.3) mmol/l) and in 24 age matched male, non-smoking controls (52.0 (7.6) years, cholesterol 4.5 (0.6) mmol/l) by positron emission tomography (PET). Resting and hyperaemic MBF and CFR (hyperaemic/resting MBF) were reduced in patients compared with controls (0.99 (0.17) v 1.17 (0.25) ml/g/min, p < 0.05; 1.37 (0.32) v 3.44 (0.78) ml/g/min, p < 0.0001; and 1.41 (0.39) v 3.03 (0.85), p < 0.0001, respectively). This coronary microvascular dysfunction was independent of cholesterol concentrations. PET was repeated in five patients after 10.1 (2.3) months of ERT; resting and hyperaemic MBF and CFR were unchanged after ERT (0.99 (0.16) v 0.99 (0.16) ml/g/min; 1.56 (0.29) v 1.71 (0.3) ml/g/min; and 1.6 (0.37) v 1.74 (0.28), respectively; all not significant). CONCLUSIONS: The results of the present study show that patients with AFD have very abnormal coronary microvascular function. These preliminary data suggest that ERT has no effect on coronary microvascular dysfunction. Further work is necessary to determine whether treatment at an earlier stage in the course of the disease may improve coronary microvascular function in patients with AFD.

Adult↗
PubMed2005

Fabry disease and the heart: an overview of the natural history and the effect of enzyme replacement therapy.

UNLABELLED: Fabry disease is a genetic disorder caused by the deficiency of alpha-galactosidase A, resulting in the lysosomal accumulation of glycosphingolipids. Fabry disease may result in cardiac, cerebral and renal complications. Cardiac abnormalities in patients with Fabry disease were first described in the 1960s. In the 1990s a form of Fabry disease confined to the heart was reported; however, this variant is extremely rare and a more appropriate concept is of cardiac predominance of the disease in some patients. Up to 60% of males with classic Fabry disease have cardiac abnormalities, including left ventricular hypertrophy, valvular dysfunction and conduction abnormalities. Recent data suggest that left ventricular mass and systolic function in patients with Fabry disease improve after 12 months of enzyme replacement therapy (ERT); however, many of the patients studied are relatively young and have mild cardiac abnormalities, suggesting that more research into the efficacy of ERT in older patients is necessary. CONCLUSION: Cardiac manifestations are common in patients with Fabry disease and are not confined to a 'cardiac variant' of the disease.

Cardiomyopathies↗
PubMed2005

Prevalence and clinical significance of systolic impairment in hypertrophic cardiomyopathy.

OBJECTIVES: To determine the frequency of systolic impairment (SI) and its impact on the natural history of hypertrophic cardiomyopathy (HCM). METHODS: 1080 patients (mean (SD) age 43 (15) years, 660 men) with HCM were evaluated. Initial assessment included history, examination, 48 hour Holter monitoring, cardiopulmonary exercise testing, and echocardiography; SI was defined as a fractional shortening (FS) < or = 25%. Survival data were collected at clinic visits or by direct communication with patients and their general practitioners. The results of serial echocardiography in 462 patients with normal FS at presentation are also reported. RESULTS: 26 (2.4%) patients (49 (14) years, 18 men) had SI at the initial visit. During follow up (58 (49) months), nine (34.6%) died or underwent cardiac transplantation compared with 108 (10.2%) patients with normal FS (p = 0.01). Five year survival from death (any cause) or transplantation was 90.1% (95% confidence interval (CI) 87.8 to 92.4) in patients with normal systolic function versus 52.4% (95% CI 25.2 to 79.6, p < 0.0001) in patients with SI. In patients who underwent serial echocardiography, 22 (4.8%, aged 41 (15) years) developed SI over 66 (40) months; the annual incidence of SI was 0.87% (95% CI 0.54 to 1.31). On initial evaluation patients who developed SI had a higher frequency of syncope (67 (15.2%) v 10 (45.5%) of those who did not develop SI, p = 0.001), non-sustained ventricular tachycardia (91 (20.6%) v 11 (50%), p = 0.002), and an abnormal blood pressure response on exercise (131 (29.7%) v 15 (68.2%), p = 0.001). Patients with SI had greater wall thinning (p = 0.001), left ventricular cavity enlargement (p < 0.0005), and deterioration in New York Heart Association functional class (p = 0.001) during follow up. Thirteen (59.1%) patients who progressed to SI died or underwent transplantation compared with 38 (8.6%) patients who maintained normal systolic function. CONCLUSIONS: SI is an infrequent complication of HCM but, when present, is associated with a poor prognosis.

Adolescent↗
PubMed2005

Myocardial late gadolinium enhancement cardiovascular magnetic resonance in hypertrophic cardiomyopathy caused by mutations in troponin I.

OBJECTIVE: To examine the influence of genotype on late gadolinium enhancement (LGE) and the potential of cardiovascular magnetic resonance (CMR) to detect preclinical hypertrophic cardiomyopathy. DESIGN: Prospective, blinded cohort study of myocardial LGE in a genetically homogeneous population. PATIENTS: 30 patients with disease causing mutations in the recognised hypertrophic cardiomyopathy gene for cardiac troponin I (TNNI3): 15 with echocardiographically determined left ventricular hypertrophy (LVH+) and 15 without (LVH-). MAIN OUTCOME MEASURES: CMR measures of regional left ventricular function, wall thickness, and mass, and the extent and distribution of LGE. RESULTS: LGE was found in 12 (80%) LVH+ patients but with variable extent (mean 15%, range 3-48%). LGE was also found in two (13%) LVH- patients but the extent was limited (3.6%) and both patients were found to have an abnormal ECG and regional hypertrophy by cine CMR. The extent of LGE was positively associated with clinical markers of sudden death risk (21% with > or = 2 risk factors v 7% with < or = 1 risk factor, p = 0.02) and left ventricular mass (r = 0.56, p < 0.001) and was inversely associated with ejection fraction (r = -0.58, p < 0.001). Segmental analysis showed that as regional wall thickness increased, LGE was more prevalent (p < 0.0001) and more extensive (r = 0.98, p = 0.001). CONCLUSION: In patients with disease causing mutations in TNNI3, focal fibrosis was not detected by LGE CMR before LVH and ECG abnormalities were present. Once LVH is present, LGE is common and the extent correlates with adverse clinical parameters. This suggests that focal fibrosis is closely linked to disease development.

Adolescent↗
PubMed2003

Pregnancy related complications in women with hypertrophic cardiomyopathy.

OBJECTIVES: To determine whether pregnancy is well tolerated in hypertrophic cardiomyopathy. SETTING: Referral clinic. DESIGN: The study cohort comprised 127 consecutively referred women with hypertrophic cardiomyopathy. Forty (31.5%) underwent clinical evaluation before pregnancy. The remaining 87 (68.5%) were referred after their first pregnancy. All underwent history, examination, electrocardiography, and echocardiography. Pregnancy related symptoms and complications were determined by questionnaire and review of medical and obstetric records where available. RESULTS: There were 271 pregnancies in total. Thirty six (28.3%) women reported cardiac symptoms in pregnancy. Over 90% of these women had been symptomatic before pregnancy. Symptoms deteriorated during pregnancy in fewer than 10%. Of the 36 women with symptoms during pregnancy, 30 had further pregnancies. Symptoms reoccurred in 18 (60%); symptomatic deterioration was not reported. Heart failure occurred postnatally in two women (1.6%). No complications were reported in 19 (15%) women who underwent general anaesthesia and in 22 (17.4%) women who received epidural anaesthesia, three of whom had a significant left ventricular outflow tract gradient at diagnosis after pregnancy. Three unexplained intrauterine deaths occurred in women taking cardiac medication throughout pregnancy. No echocardiographic or clinical feature was a useful indicator of pregnancy related complications. CONCLUSIONS: Most women with hypertrophic cardiomyopathy tolerate pregnancy well. However, rare complications can occur and therefore planned delivery and fetal monitoring are still required for some patients.

Adult↗
PubMed2002

Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy.

BACKGROUND: Although studies have suggested that "late-onset" hypertrophic cardiomyopathy (HCM) may be caused by sarcomeric protein gene mutations, the cause of HCM in the majority of patients is unknown. This study determined the prevalence of a potentially treatable cause of hypertrophy, Anderson-Fabry disease, in a HCM referral population. METHODS AND RESULTS: Plasma alpha-galactosidase A (alpha-Gal) was measured in 79 men with HCM who were diagnosed at > or =40 years of age (52.9+/-7.7 years; range, 40-71 years) and in 74 men who were diagnosed at <40 years (25.9+/-9.2 years; range, 8-39 years). Five patients (6.3%) with late-onset disease and 1 patient (1.4%) diagnosed at <40 years had low alpha-Gal activity. Of these 6 patients, 3 had angina, 4 were in New York Heart Association class 2, 5 had palpitations, and 2 had a history of syncope. Hypertrophy was concentric in 5 patients and asymmetric in 1 patient. One patient had left ventricular outflow tract obstruction. All patients with low alpha-Gal activity had alpha-Gal gene mutations. CONCLUSION: Anderson-Fabry disease should be considered in all cases of unexplained hypertrophy. Its recognition is important given the advent of specific replacement enzyme therapy.

Adolescent↗
PubMed2002

Septal myotomy-myectomy and transcoronary septal alcohol ablation in hypertrophic obstructive cardiomyopathy. A comparison of clinical, haemodynamic and exercise outcomes.

AIMS: Surgical myectomy has been successfully used to treat patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM). More recently, alcohol septal ablation has been advocated as a less invasive, but equally effective alternative therapy. The aim of this non-randomized cohort study was to compare subjective and objective outcomes in patients undergoing these therapies. METHODS: Forty-four patients (25 male; age 41+/-15 years) with symptomatic drug-refractory obstructive HCM were studied. Twenty-four patients underwent surgical myectomy and 20 alcohol septal ablation. All patients underwent clinical evaluation, echocardiography and upright maximal cardiopulmonary exercise testing using a cycle ergometer before and following their intervention. RESULTS: Peak gradient was reduced to a similar extent by both modalities (myectomy: 83+/-23 to 15+/-10 mmHg (P<0.000001); ablation: 91+/-18 to 22+/-14 mmHg (P<0.000002);P =0.48 for myectomy vs ablation) and led to similar improvements in NYHA class (myectomy: 2.4+/-0.6 to 1.5+/-0.7 (P<0.00001); ablation: 2.3+/-0.5 to 1.7+/-0.8 (P<0.0001);P=0.3 for myectomy vs ablation). Myectomy resulted in a greater improvement in peak oxygen consumption (myectomy: 16.4+/-5.8 to 23.1+/-7.1 ml.kg(-1) min(-1) (P<0.00002); ablation: 16.2+/-5.2 to 19.3+/-6.1 ml.kg(-1) min(-1) (P<0.05);P <0.05 for myectomy vs ablation) and work rate achieved (myectomy: 130+/-57 to 161+/-60 watts (P<0.04); ablation: 121+/-53 to 137+/-51 watts (P=0.11);P <0.05 for myectomy vs ablation). CONCLUSION: Surgical myectomy and alcohol septal ablation are equally effective at reducing obstruction and subjective exercise limitation in appropriately selected patients. However, the superior effect of surgical myectomy on exercise test parameters suggests that surgery remains the gold standard against which new treatment modalities should be compared.

Adult↗
PubMed2002

Isolated cardiac manifestations in Fabry disease: the UK experience.

UNLABELLED: Cardiac abnormalities are common in patients with Fabry disease, and may be the only clinical manifestation of the disease in some patients. At St George's Hospital Medical School, a national referral centre for hypertrophic cardiomyopathy in the UK, a study of 153 consecutively referred male patients revealed that 4% had Fabry disease. This increased to 6% in patients over 40 years of age. All these patients had electrocardiographic (ECG) abnormalities, most of which were consistent with those found in patients with classic Fabry disease: left ventricular hypertrophy, repolarization abnormalities and a prolonged QRS complex. A study of heterozygote females with Fabry disease also showed ECG and echocardiographic abnormalities in most patients. CONCLUSIONS: Fabry disease should be considered in the differential diagnosis of otherwise unexplained cardiac disease.

Age Factors↗
PubMed2002

Left ventricular diastolic function assessed using Doppler tissue imaging in patients with hypertrophic cardiomyopathy: relation to symptoms and exercise capacity.

BACKGROUND: Conventional Doppler indices of left ventricular diastolic function do not correlate with symptoms or exercise capacity in patients with hypertrophic cardiomyopathy, because of their dependence on loading conditions. Diastolic mitral annular velocity measured using Doppler tissue imaging has been reported to be a preload independent index of left ventricular diastolic function. OBJECTIVE: To determine the relation between diastolic annular velocities combined with conventional Doppler indices and symptoms or exercise capacity in hypertrophic cardiomyopathy. METHODS: 85 patients with hypertrophic cardiomyopathy and 60 normal controls were studied. Diastolic mitral annular velocities, transmitral left ventricular filling, and pulmonary venous velocities were measured. RESULTS: Early diastolic velocities at lateral and septal annulus were lower in patients with hypertrophic cardiomyopathy than in controls (lateral Ea: 10 (3) v 18 (4) cm/s, p < 0.0001; septal Ea: 7 (2) v 12 (3) cm/s, p < 0.0001). Unlike conventional Doppler indices alone, transmitral early left ventricular filling velocity (E) to lateral Ea ratio correlated inversely with peak oxygen consumption (r = -0.42, p < 0.0001). Patients in New York Heart Association (NYHA) class III had a higher transmitral E to lateral Ea ratio (12.0 (4.6)) than those in NYHA class II (7.6 (3.1), p < 0.005) or class I (6.6 (2.6), p < 0.0001). CONCLUSIONS: Early diastolic mitral annular velocities are reduced in patients with hypertrophic cardiomyopathy. Unlike conventional Doppler indices alone, the transmitral E to lateral Ea ratio correlates with NYHA functional class and exercise capacity.

Adolescent↗
PubMed2001

Hypertrophic cardiomyopathy: histopathological features of sudden death in cardiac troponin T disease.

BACKGROUND: Patients with hypertrophic cardiomyopathy (HCM) are at increased risk of premature death; this is particularly apparent for patients with mutations of the troponin T gene. Myocyte disarray and interstitial fibrosis, pathological features of HCM, may be determinants in these deaths. The relation between genotype, pathological phenotype, and mode of death has not been explored. METHODS AND RESULTS: Seventy-five hearts with HCM were examined. DNA was available in 50 for screening of the troponin T gene. The macroscopic findings, percentage of disarray, percentage of fibrosis, and percentage of small-vessel disease were correlated with the genotype. A troponin T mutation was identified in 9 of the 50 patients, 8 of whom died suddenly. Patients with a troponin T mutation were younger (mean age, 21.0 years [range, 6 to 37] versus 39.1 years [range, 14 to 72]; P<0.0001), had more sudden death (P=0.02), and had lower heart weights, less fibrosis, and greater disarray than other HCM patients (mean heart weight, 380.3+/-105.4 versus 585.0+/-245.7 g, P=0.002; mean fibrosis, 0.7+/-0.4% versus 2.6+/-2.8%, P=0.001; mean disarray, 46.2+/-7.2% versus 24.1+/-15.9%, P<0.0001; and mean small-vessel disease, 11.7+/-14.6 versus 14.1+/-8.7, P=0.6, respectively). Similarly, patients with troponin T mutations who died suddenly had lower heart weights and greater disarray than patients who died suddenly with unknown genotype (ie, troponin T mutation excluded) (mean heart weight, 429.8+/-75.4 versus 559.6+/-204.43 g, P=0.04, and mean disarray, 40.1+/-9.4% versus 20.2+/-12.6%, P=0.002, respectively). CONCLUSIONS: Patients with troponin T mutations had severe disarray, with only mild hypertrophy and fibrosis. These patients died suddenly and at an especially early age. We propose that extensive myocyte disarray in the absence of marked hypertrophy is the pathological substrate for sudden death in these patients.

Adolescent↗