Coronary revascularisation for postischaemic heart failure: how myocardial viability affects survival

OBJECTIVE—To assess the impact of revascularisation of viable myocardium on survival in patients with postischaemic heart failure.
METHODS—35 patients (mean (SD) age 58 (7) years) with severe heart failure (New York Heart Association (NYHA) functional class ⩾ III), mean left ventricular ejection fraction (LVEF) 24 (7)% (range 10-35%), and limited exercise capacity (peak oxygen consumption (VO₂) 15 (4) ml/kg/min) were studied. 21/35 patients had no angina. Myocardial viability was assessed with quantitative positron emission tomography and the glucose analogue ¹⁸F-fluorodeoxyglucose (FDG) (viable segment = FDG uptake ⩾ 0.25 µmol/min/g) in all patients before coronary artery bypass grafting. Patients were divided into two groups: group 1, ⩾ 8 viable dysfunctional segments (mean 12 (2), range 8-15); and group 2, < 8 viable dysfunctional segments (mean 3.5 (3), range 0-7). The two groups were comparable for age, sex, NYHA class, LVEF, and peak VO₂.
RESULTS—Two patients died perioperatively and seven patients died during follow up (mean 33 (14) months). All deaths were from cardiac causes. Kaplan-Meyer survival analysis showed 86% survival for group 1 patients versus 57% for group 2 (p = 0.03). Analysis by Cox proportional hazard model revealed three independent factors for cardiac event free survival: presence of ⩾ 8 viable segments (p = 0.006); preoperative LVEF (p = 0.002); and patient age (p = 0.01).
CONCLUSION—Revascularisation for postischaemic heart failure can be associated with good survival, which is critically dependent upon the amount of viable myocardium.


     

Reduced-intensity conditioning is effective and safe for transplantation of patients with Shwachman-Diamond syndrome

Allogeneic hematopoietic stem cell transplantation (HSCT) is the only potentially curative treatment for the BM dysfunction seen in patients with Shwachman-Diamond syndrome (SDS). Historically, these patients have fared poorly with intensive conditioning regimens with increased regimen-related toxicity especially involving the heart and lungs. We report our institutional experience with a reduced-intensity-conditioning protocol in seven patients with SDS and BM aplasia or myelodysplastic syndrome/AML. The preparative regimen consisted of Campath-1H, fludarabine and melphalan. Four patients received matched related marrow and three received unrelated stem cells (two PBSCs and one marrow). All but one was 8 of 8 allele HLA matched. All patients established 100% donor-derived hematopoiesis. No patient in this cohort developed grades III-IV GVHD. One patient had grade II skin GVHD that responded to systemic corticosteroids and one had grade I skin GVHD, treated with topical corticosteroids. Two out of seven patients developed bacterial infections in the early post transplant period. Viral infections were seen in four out of seven patients and were successfully treated with appropriate antiviral therapy. All patients are currently alive. These data indicate that HSCT with reduced-intensity conditioning is feasible in patients with SDS and associated with excellent donor cell engraftment and modest morbidity.     

Calcium channel blockade as primary therapy for stable angina pectoris. A double-blind placebo-controlled comparison of verapamil and propranolol

The effectiveness and safety of the beta-adrenergic blocking agent propranolol and the calcium channel antagonist verapamil were compared in 22 patients with chronic stable angina pectoris using a double-blind randomized placebo-controlled crossover protocol. The double-blind phase was preceded by a 2 week single-blind placebo period, followed by randomization to either 4 weeks' therapy with verapamil, 360 mg/day, or propranolol, 240 mg/day, followed by crossover to the other drug. Both verapamil and propranolol increased exercise tolerance (5.5 +/- 0.4 minutes with placebo, 7.8 +/- 0.5 minutes with propranolol [p less than 0.001], and 9.1 +/- 0.5 minutes with verapamil [p less than 0.001]), but the increase with verapamil was significantly greater (p less than 0.01). Both drugs prolonged the exercise duration to 1 mm S-T depression (3.3 +/- 0.4 minutes with placebo, 5.7 +/- 0.5 minutes with propranolol [p less than 0.001] and 5.5 +/- 0.6 minutes with verapamil [p less than 0.001]); the degree of improvement was similar with both active drugs. Both drugs decreased the resting heart rate (76 +/- 3 beats/min with placebo, 56 +/- 2 beats/min with propranolol [p less than 0.001], and 71 +/- 3 beats/min with verapamil [p less than 0.01]), but the heart rate decreased more with propranolol than with verapamil (p less than 0.001). Neither drug produced significant adverse reactions. This study, along with 8 similar double-blind placebo-controlled randomized investigations which have compared verapamil with propranolol, indicate that verapamil is as effective and safe as propranolol in relieving symptoms and improving exercise tolerance in patients with chronic stable angina pectoris and may be considered a first-line therapeutic agent in patients with ischemic heart disease.     

Correlations of fibrosis in endomyocardial biopsies from patients with aortic valve disease.

The amount of fibrosis in endomyocardial biopsies from 55 patients with aortic stenosis and 42 patients with aortic regurgitaion was measured. Sixty per cent of the patients with aortic stenosis had some degree of fibrosis; the degree of fibrosis correlated strongly with ejection fraction, peak systolic gradient, symptoms of cardiac failure, and mortality. In patients with aortic regurgitation, fibrosis was found in 40 per cent and was never severe. A correlation was found with symptoms of cardiac failure and mortality at follow-up, but not with ejection fraction or degree of regurgitation.     

TSH and Thyroid Hormones Both Regulate Bone Mass

Thyrotoxicosis is associated with a high-turnover osteoporosis, which has been solely attributed to elevated thyroid hormone levels. Mice lacking the thyroid hormone receptors α and β establish a role for thyroid hormones in regulating bone remodeling. We show that TSH, which falls when thyroid hormones rise, directly suppresses bone remodeling, and that TSH receptor null mice have profound bone loss. We suggest that reduced TSH signaling contributes to hyperthyroid osteoporosis and that TSH and its receptor could become valuable drug targets.     

Prognosis of all-cause heart failure and borderline left ventricular systolic dysfunction: 5 year mortality follow-up of the Echocardiographic Heart of England Screening Study (ECHOES).

AIMS: Heart failure (HF) is reported to have an essentially malignant prognosis that can be modified by several interventions. Most outcome data on HF are available from randomized controlled treatment trials and longitudinal epidemiological studies. However, for a number of reasons, neither type of study have, to date, provided generalizable data on HF mortality. Furthermore, data on the prognosis of borderline left ventricular systolic dysfunction (LVSD) are even more limited. METHODS AND RESULTS: ECHOES (Echocardiographic Heart of England Screening Study) screened a total of 6,162 patients from a total of 10,161 invited (61% response rate). Patients were randomly selected from four pre-specified cohorts: the general population, diuretic users, those with a prior clinical label of HF, and a population with risk factors for HF, to identify the prevalence of HF and LVSD based on clinical assessment, ECG, and echocardiography. Causes of death during a 5-9 year follow-up period were recorded from routine mortality statistics. The 5-year survival rate of the general population was 93%, compared with 69% of those with LVSD without HF, 62% with HF and no LVSD, and 53% with HF plus LVSD. Survival improved significantly with increasing ejection fraction (EF) (log rank test for trend, chi(2) = 534.5, 1, P < 0.0001). CONCLUSION: The ECHOES mortality data confirm the poor prognosis of patients suffering prevalent HF across the community with a mortality risk estimate of 9% per year. Borderline systolic dysfunction (EF 40-50%) on echocardiography carries a poor prognosis.     

Hepatitis B immunisation among invasive cardiologists: poor compliance with United Kingdom guidelines.

OBJECTIVES--To assess the compliance of invasive cardiologists in the United Kingdom with recently accepted national guidelines on the protection of health care workers and patients from hepatitis B. To determine levels of awareness of the infectivity and prevalence of the virus and current attitudes towards screening of patients before cardiac catheterisation and surgery. DESIGN--Anonymous postal survey by questionnaire from the University Hospital of Wales, Cardiff. The questionnaire established the respondent's position, knowledge of hepatitis B, current immunological state, and policy towards the routine screening of patients for hepatitis B carriage. PARTICIPANTS--All British cardiologists of consultant or senior registrar grade involved in invasive procedures. RESULTS--The response rate was 78% (211/271). 20% of respondents had never been vaccinated against hepatitis B and about a third of those vaccinated had not complied correctly with the recommended immunisation regimen. There was little uniformity in practices for screening patients for hepatitis B carriage before invasive procedures, and the level of knowledge concerning the prevalence of hepatitis B and the risks of inoculation was poor. CONCLUSIONS--Invasive cardiologists are at high risk of inoculation with hepatitis B. Nationally agreed guidelines are designed to protect both medical staff and patients against the risk of infection but currently they are ill heeded.