Reliable exclusion of prognostically significant coronary disease in left ventricular dysfunction by cardiac MRI.

AIM: To assess the ability of cardiac magnetic resonance (CMR) to exclude prognostically significant coronary artery disease (CAD) in patients with left ventricular systolic dysfunction (LVSD). MATERIALS AND METHODS: A cohort of patients who underwent both X-ray angiography and CMR since 2006 was reviewed retrospectively. Records of those with European criteria for LVSD (left ventricular ejection fraction [LVEF] <50% or LV end-diastolic volume index [LVEDVI] ≥97 ml/m2) on CMR or transthoracic echo were analysed. The presence and extent of subendocardial late gadolinium enhancement (LGE) was recorded with the 17-segment model. The degree of coronary stenosis at X-ray angiography was assessed visually and significant disease defined as stenosis of the LMS ≥50%, or proximal left anterior descending ≥75%, or ≥70% in two main coronary vessels. RESULTS: One hundred and sixteen patients were included. The mean age was 64 years and 78% were male. The mean LVEF was 40%. The prevalence of prognostic CAD was 47%. The presence of subendocardial LGE detected prognostically significant CAD with a sensitivity of 100% (95% CI: 94-100%) with no false-negative results. CONCLUSIONS: The absence of subendocardial LGE on CMR reliably excludes prognostic CAD in patients with LVSD.

Acute myocarditis secondary to Campylobacter jejuni enterocolitis.

Myocarditis is a rare condition that can mimic an acute coronary syndrome (ACS). We present the case of a 24-year-old male with Noonan syndrome who presented with a diarrhoeal pro-dromal illness, acute onset chest pain, elevated cardiac biomarkers and an abnormal ECG with ST elevation in the absence of obstructive coronary artery disease. The patient had acute myocarditis secondary to Campylobacter jejuni enterocolitis. Infective myocarditis is most commonly due to a viral infection. Myocarditis is very rarely due to a bacterial infection with only isolated reports of myocarditis induced by Campylobacter jejuni infection. At follow-up he remains well. Myocarditis should be considered in all patients presenting with acute onset chest pain and elevated cardiac biomarkers.

Mitochondrial dysfunction in Friedreich's ataxia: from pathogenesis to treatment perspectives.

Friedreich's ataxia (FRDA), the most common inherited ataxia, is an autosomal recessive degenerative disorder caused by a GAA triplet expansion or point mutations in the FRDA gene on chromosome 9q13. The FRDA gene product, frataxin, is a widely expressed mitochondrial protein, which is severely reduced in FRDA patients. The demonstration that deficit of frataxin in FRDA is associated with mitochondrial iron accumulation, increased sensitivity to oxidative stress, deficit of respiratory chain complex activities and in vivo impairment of cardiac and skeletal muscle tissue energy metabolism, has established FRDA as a "new" nuclear encoded mitochondrial disease. Pilot studies have shown the potential effect of antioxidant therapy based on idebenone or coenzyme Q10 plus Vitamin E administration in this condition and provide a strong rationale for designing larger randomized clinical trials.

Left ventricular remodelling and brain natriuretic peptide after first myocardial infarction.

OBJECTIVE: To investigate the relation between brain natriuretic peptide (BNP) concentrations and left ventricular remodelling characteristics after acute myocardial infarction. DESIGN: Consecutive sample prospective cohort study. SETTING: District general hospital coronary care unit in the north of England. PATIENTS: 133 initial survivors of a first myocardial infarction who received thrombolytic treatment. INTERVENTIONS: Patients had transthoracic echocardiography and BNP concentrations measured at three to seven days (early) and two months (late). MAIN OUTCOME MEASURES: Wall motion index 10% also had higher early and late BNP concentrations (early BNP p = 0.034 and late BNP p = 0.001). Early BNP was significantly associated with one year mortality (p = 0.003). CONCLUSIONS: Higher BNP concentrations early after first myocardial infarction are associated with adverse left ventricular remodelling characteristics. This may help explain why BNP is such a strong predictor of outcome after myocardial infarction.

Antioxidant treatment improves in vivo cardiac and skeletal muscle bioenergetics in patients with Friedreich's ataxia.

Friedreich's ataxia (FA) is the most common form of autosomal recessive spinocerebellar ataxia and is often associated with a cardiomyopathy. The disease is caused by an expanded intronic GAA repeat, which results in deficiency of a mitochondrial protein called frataxin. In the yeast YFH1 knockout model of the disease there is evidence that frataxin deficiency leads to a severe defect of mitochondrial respiration, intramitochondrial iron accumulation, and associated production of oxygen free radicals. Recently, the analysis of FA cardiac and skeletal muscle samples and in vivo phosphorus magnetic resonance spectroscopy (31P-MRS) has confirmed the deficits of respiratory chain complexes in these tissues. The role of oxidative stress in FA is further supported by the accumulation of iron and decreased aconitase activities in cardiac muscle. We used 31P-MRS to evaluate the effect of 6 months of antioxidant treatment (Coenzyme Q10 400 mg/day, vitamin E 2,100 IU/day) on cardiac and calf muscle energy metabolism in 10 FA patients. After only 3 months of treatment, the cardiac phosphocreatine to ATP ratio showed a mean relative increase to 178% (p = 0.03) and the maximum rate of skeletal muscle mitochondrial ATP production increased to 139% (p = 0.01) of their respective baseline values in the FA patients. These improvements, greater in prehypertrophic hearts and in the muscle of patients with longer GAA repeats, were sustained after 6 months of therapy. The neurological and echocardiographic evaluations did not show any consistent benefits of the therapy after 6 months. This study demonstrates partial reversal of a surrogate biochemical marker in FA with antioxidant therapy and supports the evaluation of such therapy as a disease-modifying strategy in this neurodegenerative disorder.

Impact of first myocardial infarction on self-perceived health status.

Despite recent advances in the acute management of myocardial infarction (MI), few studies have evaluated self-perceived quality of life in the longer term after MI. We mailed a questionnaire incorporating the short form 12 (SF-12) and seeking information on symptoms, drug therapy, recent investigations and employment status, to 149 patients who had a first MI 2 years previously. The response rate was 82%. Mean physical and mental summary scores were significantly lower in patients than "normative" controls (physical summary score: 37.0+/-11.5 vs. 50.9+/-9.4; p<0.001 and mental summary score: 46.2+/-12.8 vs. 52.1+/-8.7; p<0.001, respectively). Physical and mental summary scores were closely associated with continuing chest pain at 2 years, level of limitation on daily activities and employment status. We found the SF-12 to be a useful tool for monitoring health status and believe it could be used to evaluate the impact of interventions on quality of life after acute MI. Self-perceived health status 2 years after a first MI remains poor despite advances in management.

Magnetic resonance spectroscopy evidence of abnormal cardiac energetics in Xp21 muscular dystrophy.

OBJECTIVES: Our aim was to measure the cardiac phosphocreatine to adenosine triphosphate ratio (PCr/ATP) noninvasively in patients and carriers of Xp21 muscular dystrophy and to correlate the results with left ventricular (LV) function as measured by echocardiography. BACKGROUND: Duchenne and Becker muscular dystrophy (the Xp21 dystrophies) are associated with the absence or altered expression of dystrophin in cardiac and skeletal muscles. They are frequently complicated by cardiac hypertrophy and dilated cardiomyopathy. The main role of dystrophin is believed to be structural, but it may also be involved in signaling processes. Defects in energy metabolism have been found in skeletal muscle in patients with Xp21 muscular dystrophy. We therefore hypothesized that a defect in energy metabolism may be part of the mechanism leading to the cardiomyopathy of Xp21 muscular dystrophy. METHODS: Thirteen men with Becker muscular dystrophy, 10 female carriers and 23 control subjects were studied using phosphorus-31 magnetic resonance spectroscopy and echocardiography. RESULTS: The PCr/ATP was significantly reduced in patients (1.55+/-0.37) and carriers (1.37+/-0.25) as compared with control subjects (2.44+/-0.33; p<0.0001 for both groups). The PCr/ATP did not correlate with LV ejection fraction or mass index. CONCLUSIONS: Altered expression of dystrophin leads to a reduction in the PCr/ATP. Since this reduction did not correlate with indexes of left ventricular function, this raises the possibility of a direct link between altered dystrophin expression and the development of cardiomyopathy in such patients.

Reversal of severe pulmonary hypertension with beta blockade in a patient with end stage left ventricular failure.

A 52 year old man with severe chronic left ventricular failure (New York Heart Association class IV) was considered unsuitable for cardiac transplantation because of high and irreversible pulmonary vascular resistance (PVR). In an attempt to produce symptomatic improvement, metoprolol was cautiously introduced, initially at 6.25 mg twice daily. This was slowly increased to 50 mg twice daily over a two month period and continued thereafter. After four months of treatment the patient's symptoms had improved dramatically. His exercise tolerance had increased and diuretic requirements reduced to frusemide 160 mg/day only. Assessment of right heart pressures was repeated and, other than a drop in resting heart rate, there was little change in his pulmonary artery pressure or PVR. His right heart pressures were reassessed showing a pronounced reduction in pulmonary artery pressure and a significant reduction in PVR, which fell further with inhaled oxygen and sublingual nitrates. He was then accepted onto the active waiting list for cardiac transplantation. A possible mechanism of action was investigated by assessing responses to beta agonists during treatment. Not only was there pronounced improvement in PVR but it was also demonstrated that beta receptor subtype cross-regulation may have contributed to the mechanism of benefit.

Permanent cardiac pacing in elderly patients with recurrent falls, dizziness and syncope, and a hypersensitive cardioinhibitory reflex.

The study was designed to assess the outcome of treatment with permanent dual-chamber pacing of elderly patients with falls, dizziness and syncope associated with the demonstration of a hypersensitive cardioinhibitory reflex. Questionnaires were sent to patients (and their general practitioners) who had been referred to a regional pacing centre with recurrent falls, dizziness or syncope diagnosed as likely to be secondary to cardioinhibitory carotid sinus syndrome or predominantly cardioinhibitory vasovagal syndrome. After pacemaker insertion, 84% of patients had no further syncope over a mean follow-up period of 10 (range 1.5 to 30) months. Minor symptoms persisted in only 40% of all patients. Symptoms were unchanged in 22%. It was concluded that permanent dual-chamber pacing is an effective treatment for elderly patients with recurrent falls, dizziness and syncope in whom a hypersensitive cardioinhibitory reflex is found. Good results were obtained in this group with a simple diagnostic work-up.

Papillary endothelial hyperplasia in a TEC coronary atherectomy specimen.

Angiography in a 37 year old female with a three week history of typical crescendo angina found an 80% stenosis of the proximal left anterior descending (LAD) artery. The patient underwent percutaneous transluminal coronary angioplasty involving TEC artherectomy of the LAD artery. The specimen removed by atherectomy was found to have the appearance of papillary endothelial hyperplasia. This is an unusual histological diagnosis that occurs in association with thrombus. It is rarely found within arterial vessels and has not been reported in a coronary artery. Papillary endothelial hyperplasia is now thought to be a form of organising thrombus, probably dependent on the production of basic fibroblast growth factor by the endothelium.