Castle Hill Hospital, University of Hull, Hull UK
* Correspondence to: S D. R. Thackray, MRCP, Castle Hill Hospital, University of Hull, X-ray 3, Entrance 3, Cottingham, Hull HU16 5JQ, UK. Tel: +44-1482-624073; fax: +44-1482624071
E-mail address: simonthackray{at}hotmail.com
Received 6 November 2002; revised 21 January 2003; accepted 26 February 2003
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Abstract |
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Methods and Results Three hundred and seven patients were identified from attendance at routine pacemaker follow-up clinic. Subjects underwent a medical history and examination, 6-minute walk test and echocardiography. 94 (31%) had a left ventricular ejection fraction (LVEF) <40%, of whom 83 had symptoms of heart failure (70% NYHA II, 26% NYHA III and 4% NYHA IV). Heart failure was more prevalent in patients with single chamber compared to dual chamber pacemakers, (DDD(R) 18% vs 35% VVI(R), p<0.008), and those with chronic atrial fibrillation (AF) compared to those with sinus rhythm (42% vs 21%, p=0.003). Decreasing 6-minute walk distance, history of ischaemic heart disease and years of pacing were independently associated with the presence of heart failure (combined R=0.572, p<0.001).
Conclusions Heart failure due to left ventricular systolic dysfunction is common in the paced population. Only a minority of these had a pre-existing diagnosis and a smaller proportion were on optimal therapy. Echocardiographic screening of this high-risk population is justified to improve rates of diagnosis and treatment of heart failure.
Key Words: Heart failure Pacemakers Pacemaker syndrome Echocardiography
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1. Introduction |
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The few data that do exist describing the prevalence of heart failure come mainly from randomized studies comparing atrially to ventricularly based pacing in patients with sick sinus syndrome (SSS), and suggest that up to 40% of patients will develop symptoms of heart failure during long-term VVI(R) pacing.10,19
The present study describes in detail the prevalence of heart failure symptoms and therapies, cardiac dysfunction and exercise impairment in a large representative group of patients who have had a permanent pacemaker implanted.
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2. Methods |
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2.2. Patient selection
Three hundred and forty consecutive patients attending for routine pacemaker follow up over a six-month period were approached, with 307 (90%) agreeing to participate. Patients within all of these clinics are ungrouped as regards pacing mode, duration of pacing or any demographic or geographical characteristic. Patients were screened within 2 weeks of consent.
Inclusion criteria were permanent pacing for a period of 3 months and age over 18 years. Exclusion criteria were a recent (
1 month) history of myocardial infarction or recent cardiac surgery, patients with biventricular pacing devices or inability to give informed consent. Written informed consent was obtained from all patients. The local research ethics committee approved the study.
2.3. Study protocol
A medical history was taken from all patients by the same physician (ST) to identify:
2.4. Cardiovascular risk factors
Diabetes was defined according to conventional criteria.20A family history of premature coronary disease was defined as a first-degree relative suffering ischaemic heart disease under the age of 60 years. Smoking status was categorised as never, current or ex-smoker. Hypertension was defined as a previous blood pressure recording on two separate occasions of >140mmHg systolic or >90mmHg diastolic, or the ongoing prescription of anti-hypertensive medication.
2.5. Pre-existing diagnoses
All hospital records were screened to look for a discharge or outpatient clinic based diagnosis of heart failure. Additionally, in patients prescribed a loop diuretic by their general practitioner (GP) or patients who reported a diagnosis of heart failure made at any time, the GP was contacted to establish if a diagnosis of heart failure had been made and its duration. Angina pectoris was defined as a prior or current history of typical symptoms supported by an objective measure of ischaemia such as treadmill exercise test or perfusion scintigraphy. Myocardial infarction was defined according to World Health Organisation criteria.21Ischaemic heart disease was defined as a history of myocardial infarction, unstable angina or angiographic evidence of >50% stenosis of one or more coronary arteries. Cardiac surgery was categorised into coronary artery bypass grafting or valve surgery. Valvular heart disease was defined as echocardiographic or angiographic evidence of a haemodynamically significant valve lesion. Airways disease was classified as chronic obstructive pulmonary disease diagnosed by a respiratory physician on the basis of spirometry, or asthma diagnosed by a general practitioner or respiratory physician and requirement of regular inhaled bronchodilators. Body mass index (BMI) was defined as body weight in kg/(height in m2).
2.6. Medication use
All cardiac and concomitant non-cardiac medications were recorded. Frusemide or bumetanide doses are described in frusemide-equivalent doses, where 1mg bumetanide=40mg frusemide.
2.7. Pacing characteristics
Duration of pacing, current pacing mode, indication for pacing and rhythm at implant were recorded. Chronic AF was defined for the purposes of this study as the presence of AF, diagnosed from a 12-lead ECG for >4 weeks. Paroxysmal AF was defined as the presence of one or more episodes of AF, diagnosed on ECG or from pacemaker telemetry, reverting spontaneously or requiring cardioversion to sinus rhythm.
2.8. Symptom screening
Prior to the clinical examination and echocardiogram each patient was asked set questions, by the same physician, designed to evaluate symptoms of heart failure as follows:Q1:Do you ever experience any of the following symptoms; shortness of breath, fatigue or exercise limitation when undertaking your normal daily activities or any other activities such as moderate exercise, hobbies or sport? Q2:Do shortness of breath or fatigue ever restrict your ability to undertake your activities of daily living, such as washing, dressing, moving around the house, cooking and cleaning?Q3:Do you ever experience shortness of breath or fatigue after walking a few yards or at rest?
A positive response to any of the above questions would be counterpoised with the response What symptom exactly is it that limits you in this fashion? To ensure that it was symptoms referable to heart failure that were responsible.
Responses were categorized according to the New York Heart Association classification of severity of symptoms: A negative response to all questions=NYHA class I, a positive response to Q1 only=NYHA class II, a positive response to Q2=NYHA class III and a positive response to all questions=NYHA class IV.
2.9. Assessment of exercise capacity
Patients were excluded from exercise testing if they were clearly incapable of complying because of immobility (e.g. severe osteoarthritis, use of a wheelchair), incoordination (e.g. vertigo, neurological deficit) or refusal to undertake the test. A standardised six-minute hall walk was performed on all ambulatory patients by a cardiac technician after the echocardiogram.
2.10. Echocardiographic studies
All studies were conducted within 14 days of entry into the study using commercially available equipment (Vingmed Vivid V with a 3.4MHz electronic transducer, GE industries, USA). M-mode atrial and ventricular parameters were measured according to the recommendations of the American Society of Echocardiography.22A record was made during each echocardiogram as to whether the images used for analysis were in an intrinsic rhythm (IR) (defined as sinus rhythm, AF, AAI pacing or DDD(R) pacing with normal atrio-ventricular conduction), or in a ventricularly paced rhythm (VP) (defined as VVI(R) pacing or DDD(R) pacing with ventricular capture). Interpretation was based upon a rhythm strip recorded during the echocardiogram and a 12-lead surface ECG. Intrinsic beats were used preferentially for echocardiographic analysis. If the patient was pacing intermittently the three intrinsic beats after a paced beat and the intrinsic beat prior to a paced beat would not be used for analysis.
2.11. Echocardiographic data analysis
Echocardiographic evaluations were performed by two experienced observers (ST & NN) examining the digitised images after the original examination. The images were evaluated in random order with the observers blinded to the patient identity and were analysed by means of a commercially available offline data evaluation package (Echopac, GE Vingmed Ultrasound). Inter-observer differences of >5% in the calculation of LVEF would be reconciled by a third observer (KW). In these circumstances, each observer would undertake repeat analysis and a mean of all values used. A value for LVEF 40% was considered indicative of left ventricular (LV) systolic dysfunction. This value is at least two standard deviations below the mean for the local non-paced population, derived from an echocardiographic screening survey of the local normal population (n=300, all >45 years of age), (manuscript in preparation). LVEF was based on a Simpson's bi-plane calculation from an apical four-chamber view and two-chamber view at end systole and end diastole. Endocardial tracings were made manually. A mean from three digital loops was taken (five in AF). Mitral regurgitation was categorized according to regurgitant jet area and classified as none, mild, moderate or severe. Aortic stenosis was defined as an aortic valve gradient >20mmHg obtained from a pulsed wave Doppler recording in the proximal ascending aorta.
2.12. Mitral Doppler inflow patterns
In the apical four-chamber view a pulsed wave Doppler probe was placed at the point mid-way between the open mitral valve leaflets. Videotape of at least 10 cardiac cycles was recorded. E and A waves were analysed for peak velocity, E wave deceleration time and the degree of fusion of each E wave with either the preceding or following A wave. Fusion was defined as overlap of E and A waves such that two discrete peak velocity signals were not visible. Atrial and ventricular ectopics were not analysed.
2.13. Statistical analysis
All analyses were performed using commercially available software (SPSS®Chicago, USA). Data are reported as mean±SD. Continuous variables between groups were compared by the Student's t test for unpaired observations, multiple groups were compared using ANOVA with Tukey analysis were appropriate. Nominal data were compared by the chi-square test with Phi and Cramer's V analysis. Multiple stepwise regression analysis was performed with individual and multiple correlation co-efficient(s) quoted along with beta values, combined R-value and the standard error of the mean. Sensitivity and specificity of the 6-minute walk test were calculated from a receiver operator curve assuming a non-parametric distribution; confidence intervals for the asymptote are quoted. In all cases a p value <0.05 was considered as statistically significant.
2.14. Patient classification (Fig. 1)
Patientswere allocated into one of four groups dependent on symptoms and left ventricular ejection fraction (LVEF).Group 1: Patients with LVEF 40% and symptoms of heart failure (NYHA class II, III or IV), referred to as the heart failure-LVSD group.Group 2: Patients with LVEF
40% and no symptoms of heart failure (NYHA class I), referred to as the asymptomatic left ventricular systolic dysfunction group (asymptomatic-LVSD).Group 3: Patients with LVEF >40% and symptoms of heart failure (NYHA II, III or IV), referred to as the heart failure with preserved LV function group (heart failure-presLV).Group 4: Patients with LVEF >40% and no symptoms of heart failure, referred to as the normal group.
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3. Results |
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3.3. Medication use (Fig. 2)
Thirty-four per cent of all patients were receiving a loop diuretic (66% of the heart failure-LVSD group vs 22% of all other groups; p<0.001). Use of loop diuretics was also greater in the VVI(R) group (44% VVI(R) vs 24% DDD(R), p<0.001). Eleven of the 83 heart failure-LVSD patients (13%) were receiving spironolactone (nine in NYHA class III and IV)compared to one in all other groups combined (p<0.001). Fourteen per cent of all patients were taking an angiotensin converting enzyme (ACE) inhibitor or an angiotensin receptor blocker (ARB) (34% in the heart failure-LVSD group vs 6% in all other groups; p<0.001). Twenty-two per cent of patients were taking a beta-blocker (25% in the heart failure-LVSD group vs 17% in all other groups; p=ns). The choice of beta-blocker was varied in the heart failure-LVSD group with three taking carvedilol, three bisoprolol, five metoprolol, seven atenolol, one propranolol and two sotalol. Of the 83 patients with a study diagnosis of heart failure due to LVSD, only five (6%) were receiving the combination of an ACE inhibitor and a beta-blocker recognised for use in heart failure (carvedilol, bisoprolol or metoprolol), four of these were also receiving spironolactone.
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3.6. Ventricular function and heart failure (Table 2)
Eighty-three patients (27%) had symptoms compatible with heart failure (NYHA class IIIV) and LVEF 40%, whilst 58 (19%) had symptoms of heart failure and an LVEF
35%. A further 4% of patients had LVEF
40% without symptoms. Eighty-three patients (27%) had symptoms compatible with heart failure but a LVEF >40% while 43 (14%) had a LVEF >50%.
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Haemodynamically significant aortic stenosis was present in 16 patients (5%) and was the commonest obstructive valvular lesion. Only five of these patients were under regular cardiology review. Previously undiagnosed severe aortic stenosis (>80mmHg with associated symptoms) was observed in two patients, requiring immediate admission to hospital for assessment in one. Three patients had mitral orifice areas of <2cm/s2, all of whom were under regular cardiology surveillance. Five per cent of patients had a mitral valve prosthesis and 3% an aortic prosthesis. Intra-cardiac thrombi were seen in three patients (two ventricular mural, one attached to an atrial lead). One patient with hypertrophic cardiomyopathy (included in the analysis) and one with congenitally corrected transposition of the great vessels (excluded from the analysis) were seen.
3.7. Predicting heart failure
Using multiple stepwise regression analysis we sought to identify variables to help target screening for heart failure secondary to LV systolic dysfunction more precisely among patients with a permanent pacemaker. Factors included were: age, a diagnosis of heart failure made prior to screening, ischaemic heart disease, diabetes, hypertension, VVI(R) pacing mode, duration of pacing, pacemaker dependency at implant, chronic AF, 6-minute walk distance, prescription of an ACE inhibitor, prescription of a beta-blocker and prescription of a loop diuretic. Only 6-minute walk distance (r=0.43, p<0.001; beta=0.44, p<0.001), ischaemic heart disease (r=0.42, p<0.00; beta=0.33, p<0.001) and increasing duration of pacing in years (r=0.18, p=0.023; beta=0.18, p=0.016) were independently predictive of the presence of heart failure due to LV systolic dysfunction (combined R=0.572, SE=0.38).
3.8. 6-minute walk test
The test was performed on 235 patients (76%); a six-minute walk distance of 167m had a sensitivity of 78% and specificity of 71% for the presence or absence of heart failure due to LV systolic dysfunction (area under the curve (AUC) 0.78, 0.700.85, p<0.001). The predictive power of the 6-minute walk test increased with the duration of pacing. Sensitivity and specificity increased to 85% and 71%, respectively, if patients paced for <2 years were excluded (AUC 0.80, 0.730.87, p<0.001) and 80% and 75% if patients paced for <4 years were excluded (AUC 0.82, 0.730.91, p=0.001). No additional sensitivity or specificity accrued by targeting other subgroups, such asthose with coronary disease or those with a VVI(R) pacemaker.
3.9. Symptomatic patients with preserved systolic function
Among patients with LVEF 40% (n=213), 83 had symptoms consistent with heart failure (NYHA class II, III or IV). Compared to asymptomatic patients with preserved LV systolic function (LVEF >40%) (Table 2), symptomatic patients were older (69±13 years vs 74±10 years, p=0.005), had slightly lower LVEF (54±8% vs 52±7%, p=0.019), a shorter 6-minute walk distance (333±137m vs 168±130m, p<0.001), a higher likelihood of a pre-existing diagnosis of heart failure (6% vs 23%, p<0.001), hypertension (45% vs 68%, p=0.001) and IHD (23% vs 40%, p=0.012). Symptomatic patients were more likely to be ventricularly paced during their echocardiogram (35% vs 53%, p=0.01) have mitral regurgitation (38% vs 52%, p=0.02) and be prescribed a loop diuretic (15% vs 37%, p<0.001). Fifty-one patients (61% of symptomatic patients) had symptoms but were in sinus rhythm; 14 of these patients had VVI(R) pacemakers and demonstrated complete E and A wave dissociation, and therefore frequent E/A fusion, while 32 patients with a DDD(R) pacemaker demonstrated marked E/A fusion suggesting sub-optimal atrio-ventricular synchronization.
By stepwise regression analysis the presence of significant E/A wave fusion (r=0.21, p=0.009, beta 0.214) and lower LVEF r=0.21, p=0.009, beta=0.19) were the only variables independently associated with the presence of symptoms of heart failure in patients with pacemakers and preserved left ventricular systolic function, although thisrelationship was weak (combined R=0.29, SE of estimate 0.46).
Traditional markers of diastolic function such as E/A ratio, isovolumic relaxation time, deceleration time, left atrial size and intraventricular septal thickness showed no significant difference between the two groups.
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4. Discussion |
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Although little attention has been paid to heart failure and ventricular dysfunction in patients with pacemakers, the high prevalence should come as no surprise. Patients with pacemakers and patients with heart failure share common risk factors, being of a similar age and having a high prevalence of co-morbidities such as hypertension (62%) and coronary disease (31%). Patients with pacemakers may be at additional risk of developing heart failure either due to the nature of the underlying cardiac dysfunction or because of the pacing itself. VVI(R) pacing will impair cardiac performance by inducing atrio-ventricular dysynchrony; this can be prevented by DDD(R) pacing.26However, DDD(R) pacing can still induce inter- and intra-ventricular dysynchrony, which may impair ventricular filling, increase the severity of mitral regurgitation and reduce cardiac output.27,28Pacing may not only induce cardiac dysfunction directly but may also increase the risk of developing atrial fibrillation, an important precipitant of heart failure.29,30Patients with pacemakers have a higher prevalence of AF (26%) than an aged matched population (8%)31,32with an incidence of new onset AF of 11.4% over a mean of 5.9 years of follow-up.
The relationship between duration of pacing and the presence of heart failure is likely to be complex due to ageing, the increasing burden of co-morbidity and, potentially, the chronic effects of pacing itself. The prevalence of AF (Fig. 5) increased from around 30% initially to 46% after pacing for 10 or more years while almost 10% of patients experienced a non-fatal myocardial infarction during a mean follow-up of 4.6 years.
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The six-minute walk test is relatively easy to perform in the outpatient setting without medical supervision. In those able to perform the test, it offers a safe, cheap and convenient screening tool for the assessment of functional capacity that, in turn, may help increase awareness of the presence of heart failure. Performing the test on all possible subjects offers reasonable sensitivity (78%) and specificity (71%) for the presence of heart failure using a cut off value of 167m. The value of the test appears to increase over time with longer periods of pacing.
4.1. Limitations
Of 340 patients invited to participate in the study, only 10% failed to attend for assessment. Thecharacteristics of these patients did not differ markedly from the rest of the study population. This is unlikely to have biased our results.
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5. Conclusions |
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Acknowledgments |
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References |
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