Prognostic Significance of Incidental Nonsustained Ventricular Tachycardia Detected on Pacemaker Interrogation.

Symptomatic sustained ventricular tachycardia is a life threatening arrhythmia requiring prompt treatment. However, the risk associated with asymptomatic nonsustained ventricular tachycardia (NSVT) detected on routine permanent pacemaker (PPM) interrogation in patients with known cardiac conduction disease is unknown. Our aim is to determine if asymptomatic NSVT detected on PPM interrogation is associated with increased mortality. As part of a prospective observational cohort study, 582 patients with long-term pacemakers were recruited at a tertiary cardiac centre, and followed for 4 ± 1.96 years (mean ± standard deviation). At each subsequent pacemaker check, any symptoms and ventricular high-rate episodes were recorded. We excluded 17 patients due to incomplete data. In the remaining 565 patients (57% male, age 74.5 ± 19.2 years, left ventricular ejection fraction 50.0 ± 11.3%), NSVT was found in 125 (22.1%) patients with a higher prevalence in males (65% vs 54%; p = 0.033). Those with NSVT were more likely to have had coronary artery disease (p = 0) or previous myocardial infarction (p = 0.015). After correction for baseline variables, NSVT had no impact on survival (n = 52 [42%] vs n = 162 [37%]; log-rank p = 0.331, hazard ratio: 0.927, 95% confidence interval: 0.678 to 1.268, p = 0.697). In conclusion, asymptomatic NSVT identified on PPM interrogation does not appear to be associated with increased mortality, thus whether treatment to suppress this arrhythmia is of benefit remains unproven.

Calcium, phosphate and calcium phosphate product are markers of outcome in patients with chronic heart failure.

BACKGROUND: Serum calcium (Ca) and inorganic phosphate (Pi) concentrations and calcium-phosphate product (CPP) levels are positively associated with worse outcomes in patients with chronic kidney disease, but there are few data for Pi or Ca and none for CPP in patients with chronic heart failure (CHF). METHODS: Unselected, consecutive patients with CHF (left ventricular ejection fraction, LVEF ≤45%) were enrolled in a prospective observational study for the occurrence of hospitalisation and mortality. Blood samples were collected at the time of recruitment and analysed immediately. RESULTS: Patients (n = 713) were on contemporary optimal treatment and mean (standard error, SE) follow-up was 765 (18.9) days. Mean (SE) Ca was 2.29 (0.004) mmol/l. Median (interquartile range, IQR) Pi was 1.11 (0.98-1.23) mmol/l and median CPP 2.53 (2.21-2.88) mmol(2)/l(2). LVEF correlated inversely with Ca, natural log-transformed (Ln)Pi, and LnCPP. There was no difference in CPP between classes of symptom severity or diabetes status. Ca and LnCPP (but not LnPi) were associated with total mortality. Ca was significantly associated with progressive HF and non-cardiovascular death but not with sudden death. Binary logistic regression analyses showed that LnPi and LnCPP were associated with risk of hospitalisation. CONCLUSIONS: Ca, Pi and CPP could be useful additional variables in determining risk in CHF patients. Further work is required to elucidate the mechanisms underlying the adverse influence and determine whether lowering phosphate levels per se in CHF patients is of benefit.

Patients with long-term permanent pacemakers have a high prevalence of left ventricular dysfunction.

INTRODUCTION: Patients with right ventricular pacemakers are at increased risk of left ventricular systolic dysfunction (LVSD). We aimed to establish the prevalence, degree and associations of LVSD in patients with long-term right ventricular pacemakers listed for pulse generator replacement (PGR). METHODS: All patients listed for PGR at Leeds General Infirmary were invited to attend for an assessment during which we recorded medical history, symptomatic status, medical therapy, date and indication of first implantation, the percentage of right ventricular pacing (% RVP) and an echocardiogram. RESULTS: We collected data on 491 patients. A left ventricular ejection fraction less than 50% was observed in 40% of our cohort, however, this was much higher (59%) in those with more than 80% RVP than in those with less than 80% RVP (22%) (P < 0.0001). Multivariable analysis revealed % RVP, (but not complete heart block at baseline), serum creatinine and previous myocardial infarction to be independently related to the presence of LVSD. A model combining % RVP and previous myocardial infarction has a c-statistic of 0.74 for predicting LVSD. After a mean follow-up time of 668 days, 56 patients (12%) were dead or had been hospitalized for heart failure. In multivariable analysis, previous myocardial infarction and high % RVP were independently associated with a worse survival. CONCLUSION: Patients with right ventricular pacemakers have a high prevalence of LVSD, and this is greater in those exposed to more RVP. Those with LVSD and high amounts of RVP are at higher risk of hospitalization or death. Simple variables can identify those patients who might benefit from a more comprehensive review.

Cardiac resynchronization therapy in pacemaker-dependent patients with left ventricular dysfunction.

AIMS: Heart failure and left ventricular (LV) systolic dysfunction (LVSD) are common in patients with permanent pacemakers. The aim was to determine if cardiac resynchronization therapy (CRT) at the time of pulse generator replacement (PGR) is of benefit in patients with unavoidable RV pacing and LVSD. METHODS AND RESULTS: Fifty patients with unavoidable RV pacing, LVSD, and mild or no symptoms of heart failure, listed for PGR were randomized 1 : 1 to either standard RV-PGR (comparator) or CRT. The primary endpoint was the difference in change in LV ejection fraction (LVEF) between RV-PGR and CRT groups from baseline to 6 months. Secondary endpoints included peak oxygen consumption, quality of life, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. At 6 months there was a difference in change in median (interquartile range) LVEF [9 (6-12) vs. -1.5 (-4.5 to -0.8)%; P < 0.0001] between the CRT and RV-PGR arms. There were also improvements in exercise capacity (P = 0.007), quality of life (P = 0.03), and NT-proBNP (P = 0.007) in those randomized to CRT. After 809 (729-880) days, 17 patients had died or been hospitalized (6 in CRT group and 11 in the comparator RV-PGR group) and two patients in the RV-PGR arm had required CRT for deteriorating heart failure. Patients with standard RV-PGR had more days in hospital during follow-up than those in the CRT group [4 (2-7) vs. 11 (6-16) days; P = 0.047]. CONCLUSION: Performing CRT in pacemaker patients with unavoidable RV pacing and LVSD but without severe symptoms of heart failure, at the time of PGR, improves cardiac function, exercise capacity, quality of life, and NT-pro-BNP levels.

Marine polyunsaturated fatty acids in heart failure. Are the theoretical benefits matched by the clinical data?

Chronic heart failure (CHF) is a common condition, which despite major advances, is still characterized by high mortality (with sudden arrhythmic death a particular risk), poor quality of life due to exercise intolerance and frequent hospitalizations. Epidemiological studies suggest that populations with a high intake of marine polyunsaturated fatty acids (PUFAs or fish oils) have low levels of cardiovascular mortality. Animal and human studies of fish oil supplementation have demonstrated improved endothelial function and myocardial relaxation, reduced vascular tone and platelet aggregability, and a stabilization of myocyte excitability by prolongation of the refractory period. Marine PUFAs also have potentially important immune-modulating effects, reducing cytokine production and release, and altering prostaglandin metabolism. Data from patients following acute myocardial infarction have suggested that marine PUFA supplementation may reduce early mortality, mostly by reducing the risk of sudden arrhythmic death. Until recently, data in patients with chronic heart failure was lacking, but the recent publication of the GISSI-HF study, randomizing more than 7000 CHF patients to marine PUFA supplementation or placebo has clarified somewhat the role of these agents. The aim of this article is to review the theoretical benefits of marine PUFAs and to discuss the implications of the GISSI-HF study for the management of patients with CHF.

Dyspnoea versus fatigue: additional prognostic information from symptoms in chronic heart failure?

BACKGROUND: In non-heart failure populations, dyspnoea reported by the patient as the reason for stopping an exercise test is associated with a worse prognosis than fatigue. Patients with chronic heart failure (CHF) have exercise limitation due to breathlessness or fatigue, but it is unclear whether one symptom confers an adverse prognosis over the other. METHODS: Consecutive CHF patients underwent exercise testing with metabolic gas exchange. Upon stopping exercise the dominant symptom reported by the patients was recorded. Survival analyses were performed to establish predictors of mortality and relationships between symptoms and objective measures of exercise capacity. RESULTS: Data were analysed on 271 patients (219 men), mean age 67 (10) years, mean left ventricular ejection fraction 32 (8)%, and median follow-up 59 months (interquartile range 38). There were no differences in exercise variables, sex, NYHA class, body mass index and medical therapy between fatigued and dyspnoeic patients. At the censor date 92 (34%) patients had died. Deceased patients had a lower peak oxygen consumption (17.2 (4.6) versus 20.3 (5.6); p=0.0028). Although NYHA class was related to death at 36 months (chi2 value=7.3, p=0.026), reason for stopping was not (chi2 value=0.57, p=0.45). CONCLUSION: Unlike in non-heart failure populations, dyspnoea as the reason for stopping an exercise test in CHF subjects is not associated with increased mortality. CHF patients should be assessed for treatments such as cardiac resynchronisation therapy by the degree of exercise intolerance, not the nature of their symptoms.

Carvedilol in the treatment of elderly patients with chronic heart failure.

Chronic heart failure (CHF) is common, and increases in incidence and prevalence with age. There are compelling data demonstrating reduced mortality and hospitalizations with adrenergic blockade in older patients with CHF. Despite this, many older patients remain undertreated. The aim of the present article is to review the potential mechanisms of the benefits of adrenergic blockade in CHF and the clinical data available from the large randomized studies, focusing particularly on older patients.

Muscle sympathetic nerve activity and ventilation during exercise in subjects with and without chronic heart failure.

BACKGROUND: Changes within skeletal muscle, including augmentation of its capacity to elicit reflex increases in both efferent muscle sympathetic nerve activity (MSNA) and ventilation during work, contribute significantly to exercise intolerance in heart failure (HF). Previously, we demonstrated that peak oxygen uptake (pVO(2)) in HF relates inversely to MSNA at rest and during exercise. OBJECTIVE: To test the hypothesis that there is an independent positive relationship between resting MSNA and the ratio of ventilation to carbon dioxide output during exercise (VE/VCO(2)) that is augmented in HF. METHODS: MSNA at rest and VE/VCO(2)) during stationary cycling were measured in 30 patients (27 men) with HF (mean +/- SD ejection fraction 20+/-6%) and in 31 age-matched controls (29 men). RESULTS: MSNA was higher in HF patients than in controls (51.5+/-14.3 bursts/min versus 33.0+/-11.1 bursts/min; P<0.0001). The VE/VCO(2) slope was also higher in HF patients than in controls (33.7+/-5.7 versus 26.0+/-3.5; P<0.0001), whereas pVO(2) was lower in HF patients than in controls (18.6+/-6.6 versus 31.4+/-8.4 mL/kg/min; P<0.0001). There were significant relationships between MSNA and VE/VCO(2) in both HF (r=0.50; P=0.005) and control subjects (r=0.36; P=0.046). The slope of this regression equation was steeper in HF (0.20 versus 0.11 x MSNA; P=0.001). An analysis of covariance for main effects, including age and pVO(2), identified a significant independent relationship between MSNA burst frequency and VE/VCO(2) (P=0.013) that differed between HF and controls (P<0.01). CONCLUSIONS: The magnitude of resting sympathetic activity correlates positively with the VE/VCO(2) slope. Augmentation of this relationship in HF patients is consistent with the concept that enhanced mechanoreceptor reflex activity exaggerates their ventilatory response to exercise.

Fibrinogen synthesis is increased in cachectic patients with chronic heart failure.

INTRODUCTION: Cachexia is common in chronic heart failure (CHF) and may be due to a combination of reduced appetite, and increased metabolic rate due to immune activation. This hypermetabolism, with an increase in acute phase protein turnover, also seen in cancer cachexia, might contribute to weight loss seen in severe CHF. We investigated the rate of hepatic fibrinogen synthesis by measuring the rate of incorporation of deuterated phenylalanine into circulating plasma fibrinogen. METHODS: 14 male patients with CHF, 9 with a history of weight loss each received an infusion containing 3500 mg of l-phenylalanine and 350 mg [(2)H(5)]l-phenylalanine. Blood drawn at intervals allowed measurement of the rate of [(2)H(5)]-phenylalanine enrichment in fibrinogen by gas chromatography-mass spectrometry. RESULTS: Cachectic and non-cachectic patients had similar age and CHF severity. Cachectic patients had lower body mass index (BMI), and corrected arm muscle area (CAMA). The logarithmic derivatives of CRP and IL-6 were greater in the cachectic than the non-cachectic subjects (0.99 (0.38) v 0.44 (0.35); p=0.015 and 1.25 (0.50) v 0.86 (0.15); p=0.09). Total plasma fibrinogen (TF), relative fibrinogen synthesis rate (FSR) and absolute synthesis rate (ASR) were greater in those with cachexia. There were inverse relationships between TF and indices of body habitus: CAMA (r=0.62; p<0.02) and BMI (r=0.55; p<0.05). TF was related to CRP (r=0.69; p<0.007). CONCLUSION: Patients with CHF and cachexia have an increased hepatic fibrinogen synthesis rate related to the level of C-reactive protein. It is possible that increased protein turnover is one of the causes of weight loss in patients with severe heart failure.

Epidemiology, associated factors, and prognostic outcomes of renal artery stenosis in chronic heart failure assessed by magnetic resonance angiography.

Our aim was to determine the prevalence, morbidity, and mortality associated with the presence of significant renal artery stenosis (RAS) in patients with chronic heart failure (HF), and to explore the use of angiotensin-converting enzyme (ACE) inhibitors and diuretics in this population during a 3-year follow-up period. We identified 97 patients with significant renal dysfunction (RD, defined as a calculated glomerular filtration rate of <60 ml/min) and 38 patients without RD, with ejection fractions of <40%. A stenosis of >50% using magnetic resonance angiography of the renal arteries was used to define significant RAS. Seventy-three (54%) patients had significant RAS of >or=1 artery. Mean follow-up time was 37.3 (+/- 7.9) months. Compared with patients with no significant RAS, these patients were on higher doses of diuretics, lower doses of ACE inhibitors, had prolonged hospital admissions, were admitted with exacerbation of HF, and had a higher mortality (p = 0.007 for mortality). In conclusion, RAS is common in patients with chronic HF, especially among patients with RD and is a predictor of a poor clinical outcome. Interventional trials on renal revascularization are underway that contain subsets of patients with HF that may provide evidence on how best to manage RAS in this setting.

Effects of applying a standardised management algorithm for moderate to severe renal dysfunction in patients with chronic stable heart failure.

BACKGROUND: No specific guidelines exist on how to manage renal dysfunction (RD) in patients with chronic heart failure (CHF). AIMS: To identify the proportion of patients with moderate to severe RD and CHF who showed an improvement in their renal function in response to a systematic management algorithm. METHODS: Stable patients with CHF and RD (defined by a serum creatinine (SCr) of >130 micromol/l (>1.5 mg/dl)) were enrolled into a systematic management algorithm. The following changes were implemented: switching aspirin to clopidogrel, halving the dose of both diuretics and angiotensin converting enzyme (ACE) inhibitors and switching between bisoprolol and carvedilol. RESULTS: Two thirds of patients in whom diuretics were reduced, and one fifth of patients in whom ACE inhibitors were reduced, improved their SCr by >25.5 micromol/l (0.3 mg/dl). All these changes were more marked in the presence of bilateral renal artery stenosis. Compared to a reference group, in whom no changes were implemented, the treatment group showed an improvement in their mean SCr by 35 micromol/l (0.4 mg/dl), p<0.001. CONCLUSION: Manipulation of pharmacological therapy for patients with CHF and RD results in a substantial recovery of renal function in a minority of patients.

The effect of altering heart rate on ventricular function in patients with heart failure treated with beta-blockers.

BACKGROUND: Beta-blockers are effective for the treatment of heart failure, but their mechanism of action is unresolved. Heart rate reduction may be a central mechanism or a troublesome side effect. METHODS: A randomized, double-blind, parallel group study comparing chronic higher-rate (80 pulses per minute) with lower-rate (60 pulses per minute) pacing in pacemaker-dependent patients with symptomatic left ventricular (LV) systolic dysfunction, receiving beta-blockers. Gated radionuclide ventriculography (RNVG) was performed at baseline and after at least 9 months. The primary outcome was change in LV volumes, as a marker of beneficial reverse remodeling, from baseline to follow-up. RESULTS: Forty-nine patients were randomized. Mean age was 74 +/- 6 years and with LV ejection fraction of 26% +/- 9% at baseline. During 14 +/- 13 months of follow-up, 21 patients (43%) died and 25 (51%) completed the study protocol: 12 in the higher-rate and 13 in the lower-rate group. Mean LV end-diastolic (higher rate +20 +/- 104 mL vs lower rate -65 +/- 92 mL, P = .03) and systolic (higher rate +29 +/- 83 mL vs lower rate -60 +/- 74 mL, P = .006) volumes increased with higher-rate versus lower-rate pacing, whereas LV ejection fraction declined (higher rate -4.2% +/- 4.4% vs lower rate +2.2% +/- 5.4%, P = .002). CONCLUSION: Reversal of beta-blocker-induced bradycardia has deleterious effects on ventricular function, suggesting heart rate reduction is an important mediator of their effects. The prognosis of patients with pacemakers and heart failure is poor.

Anemia, renal dysfunction, and their interaction in patients with chronic heart failure.

Anemia and renal dysfunction (RD) are frequent complications seen in chronic heart failure (HF). However, the prevalence and interaction of these co-morbidities in a representative population of outpatients with chronic HF is poorly described. In this study, it was sought to determine the association between RD and anemia in patients with HF enrolled in a community-based HF program. Nine hundred fifty-five patients with HF due to left ventricular systolic dysfunction were investigated for the prevalence of anemia and its cause and followed for a median of 531 days. Anemia was defined as hemoglobin < 12.0 g/dl in women and < 13.0 g/dl in men. RD was defined as a calculated glomerular filtration rate of < 60 ml/min. The prevalence of anemia was 32%. Fifty-three percent of patients with and 27% of those without anemia had > or = 1 test suggesting hematinic deficiency. The prevalence of RD was 54%. Forty-one percent of patients with and 22% of patients without RD had anemia, with similar proportions associated with iron deficiency in the presence or absence of RD. Anemia and RD independently predicted a worse outcome, and this effect was additive. In conclusion, in outpatients with chronic HF, anemia and RD are common and co-exist but confer independent prognostic information. A deficiency of conventional hematinic factors may cause about 1/3 of anemia in this clinical setting.