(Circulation. 1997;96:500-508.)
© 1997 American Heart Association, Inc.
Articles |
Patients With Valvular Heart Disease Presenting With Sustained Ventricular Tachyarrhythmias or Syncope
Results of Programmed Ventricular Stimulation and Long-term Follow-up
From the Department of Cardiology and Angiology and Institute for Research in Arteriosclerosis and the Department of Cardiovascular Surgery (H.H.S.), University of Münster (Germany).
Correspondence to Dr Antoni Martínez-Rubio, Hospital de la Sta Creu i St Pau, Department of Cardiology, Avda. Antoni Ma. Claret 167, E-08025 Barcelona, Spain.
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Abstract |
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 Top Abstract IntroductionMethodsResultsDiscussionReferences |
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Background Programmed ventricular stimulation is commonly used to guide therapy in post–myocardial infarction patients with sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF). In patients with valvular heart disease presenting with spontaneous VT, VF, or syncope, the usefulness of this technique is still unclear. The aim of the study was to analyze whether programmed ventricular stimulation was helpful in guiding therapy and determining prognosis in 97 patients with valvular heart disease presenting with VT (60%), VF (18%), or syncope (22%).
Methods and Results Patients were classified as having either predominant ventricular pressure or volume overload or no significant pressure or volume overload. Overall, sustained VT or VF was inducible in 38 (39%) and 19 (20%) patients, respectively. Forty-six (47%) patients were discharged on antiarrhythmic drugs, 29 (30%) received an implantable cardioverter-defibrillator, and 22 (23%) remained without therapy. With serial drug testing, inducibility was completely or partially suppressed in 18 (19%) and 9 (9%) patients, respectively. During a mean follow-up of 51 months (n=97), 17 patients (18%) died (sudden death, n=7; heart failure, n=4; noncardiac causes, n=6). One-, 2- and 3-year event-free survival for sudden death, sustained VT, or VF was 77%, 68%, and 61%, respectively. Only inducibility of VT during baseline study (P<.0003) and left ventricular volume overload (P<.008) were significant predictors of arrhythmic events. Recurrence of arrhythmic events occurred in 56% and 56% of patients with complete or partial suppression of inducibility during serial drug testing as well as in 10 of 19 (53%) patients without a change in inducibility.
Conclusions Although programmed ventricular stimulation seems to predict adverse outcome, serial drug testing is unreliable in guiding therapy. The type of workload imposed on the ventricles influences outcome, being worse in patients with left ventricular volume overload. Therefore, implantation of a cardioverter-defibrillator should be considered early for the management of these patients.
Key Words: death, sudden • electrical stimulation • tachyarrhythmias • tachycardia • valves
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Introduction |
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Ambulatory Holter monitoring has demonstrated that sustained ventricular tachyarrhythmias are the most common (
85%) terminal event leading to sudden
death.1 2 3 In addition, several previous
studies4 5 6 7 8 9 reported on incidence of sudden death in
patients with a broad variety of types of valvular heart
disease. Programmed ventricular stimulation is commonly used to guide therapy in post–myocardial infarction patients with either sustained monomorphic ventricular tachycardia (VT) or ventricular fibrillation (VF).10 11 12 13 14 Recent data15 also point to the usefulness of electrophysiologically guided therapeutic decisions in patients with hypertrophic cardiomyopathy presenting with VT or VF. However, the role of this technique in patients with dilated cardiomyopathy remains unclear.16 17 18 Up to now, only a limited number of patients with valvular heart disease has been studied19 (mostly included as a subset in a large patient cohort with other diagnoses). Therefore, the aim of the present retrospective study was to assess the outcome of a large cohort of patients with valvular heart disease presenting with spontaneous sustained ventricular tachyarrhythmias or syncope who underwent programmed ventricular stimulation.
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Methods |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
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Patients
Ninety-seven consecutive patients with valvular heart disease who presented with either sustained VT, VF, or syncope between 1985 and 1994 were enrolled in the study. There were 33 women and 64 men, ranging in age from 15 to 75 years (mean±SD, 46±16 years). The clinical characteristics of the patients are described in Table 1
. Five patients (5%)
were receiving class I antiarrhythmic drugs prescribed for atrial
fibrillation (n=2) or frequent ventricular extrasystoles
(n=3) when they presented with sustained VT. Patients were
grouped on the basis of location and predominant
hemodynamic consequence of their valve disease.
Thirty-nine patients (40%) had undergone prosthetic valve
replacement (n=27 aortic; n=6 mitral; n=6 aortic and mitral) and 15
patients (15%) had previous corrective surgery of tetralogy of Fallot
71±75 months before their first arrhythmic event. All patients who had
not had surgery presented with mild or moderate
valvular heart disease. The group with left
ventricular pressure overload consisted of 14 patients with
predominant aortic stenosis; the group with left
ventricular volume overload (n=37) comprised 19 patients
with aortic regurgitation and 18 patients with mitral
regurgitation. The group with right
ventricular pressure overload (n=27) consisted of 7
patients with mitral stenosis, 15 patients with tetralogy of
Fallot (all after corrective surgery, with moderate pulmonary
stenosis and without significant pulmonary
insufficiency), and 2 patients with isolated pulmonary
stenosis and 3 patients with corrected transposition of the
great arteries. No significant pressure or volume overload was seen in
3 patients with Morbus Ebstein and 12 patients with mitral valve
prolapse.
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All patients underwent right and left heart
catheterization including the transseptal approach, if
necessary, as well as angiography as clinically indicated.
Coronary artery disease (defined as 
50% narrowing of the
diameter of at least one coronary artery) was always excluded
in patients older than 30 years. Angiographically determined (30 degree
right anterior oblique projection) left ventricular
ejection fraction was available in 75 patients.
Electrophysiological Study
Electrophysiological studies were performed
in all patients after written informed consent was obtained.
Antiarrhythmic drugs were discontinued at least 5 half-lives before the
study in 89 (92%) patients. Eight patients were referred to our
hospital and studied on class III antiarrhythmic drugs
(amiodarone) because recurrent sustained VT and/or atrial
fibrillation with fast ventricular rates occurred when they
were not receiving drugs. Programmed ventricular
stimulation was performed with the use of conventional intracardiac
recording and stimulation. The details of these procedures have
been reported elsewhere.11 13 Briefly, programmed
ventricular stimulation was performed with single and
double ventricular extrastimuli during sinus rhythm and
paced ventricular drive cycles of 500 ms, 430 ms, 370 ms,
and 330 ms at twice diastolic threshold at the right
ventricular apex and subsequently at the right
ventricular outflow tract. If neither VT nor VF were
inducible, a third extrastimulus was introduced at a paced cycle length
of 500 ms beginning at the right ventricular apex and
subsequently, if necessary, at the right ventricular
outflow tract. Sustained monomorphic VT was defined as VT manifesting
beat-to-beat uniform surface ECG QRS configuration that lasted >30
seconds or that was hemodynamically intolerable and
needed termination. A run of >3 ventricular echo beats
terminating within 30 seconds was defined as nonsustained VT.
Tachycardias with a cycle length <200 ms were considered
to be ventricular flutter if discrete QRS complexes were
present on the surface ECG; otherwise, they were considered to be
VF. Those patients in whom VF was initiated during the attempt to
terminate sustained VT by overdrive pacing or in whom monomorphic VT
spontaneously degenerated into fibrillation were not considered to have
primary induced VF. The end point of programmed ventricular
stimulation was the induction of a sustained ventricular
tachyarrhythmia (lasting >30 seconds or associated
with hemodynamic compromise) twice or completion of the
stimulation protocol.
Therapy
When the baseline study was completed, appropriate therapy was
initiated after the patient had received detailed information about
therapeutic options and related benefit/risk ratios. Usually, in
patients with inducible VT, serial drug testing was considered as the
first therapeutic approach. If arrhythmia induction could be
completely or partially suppressed, the patient was discharged on these
drugs. Completion of the stimulation protocol through to triple
extrastimuli during antiarrhythmic drug therapy without inducing
sustained ventricular arrhythmias was considered
complete suppression. If the induction of ventricular
tachyarrhythmia was possible on antiarrhythmic therapy
but only with use of more extrastimuli or at least at a basic drive
cycle length corresponding to 40 bpm faster than at baseline study,
this was considered partial suppression of inducibility.11
If inducibility of VT/VF was not at least partially suppressed by
antiarrhythmic drugs, nonpharmacological therapy was considered.
Proarrhythmic effects of antiarrhythmic drugs were considered in
patients who presented with VT on drugs that had been
prescribed not because of VT but atrial fibrillation or extrasystoles
and had no inducible VT without drugs but inducible VT with the same
drug. These patients were discharged without the drug that caused the
proarrhythmic effect.
Follow-up
Ambulatory and telephone interviews of the patients were
performed at least every 3 to 6 months. In case of death, family
members as well as the family physician were interviewed for detailed
circumstances of the death. Sudden death was defined as a death that
occurred instantaneously or within 1 hour after the onset of symptoms.
Follow-up was complete in all patients. The mean duration of follow-up
was 51±39 months and did not differ significantly between the
subgroups categorized according to location and
hemodynamic type of valvular heart
disease.
Data Analysis
Continuous data are presented as mean±SD.
Univariate comparisons were performed with Student's
t test, Mantel-Cox test, or 
2
analysis with the use of the Scientific Package for the Social
Sciences for Windows (SPSS release 5.0.1). In addition, Cox regression
was used for determining the independent predictors of arrhythmic event
recurrence. Kaplan-Meier analysis was performed to
analyze the survival function in relation to the occurrence of
arrhythmic event recurrences. To test the equality of this
survival distribution, the Mantel-Cox test was performed. A value of
P<.05 was considered statistically significant. To account
for multiple testing, a Bonferroni correction of the nominal
probability value was performed when appropriate.
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Results |
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Results of Programmed Ventricular Stimulation in Relation to the Presenting Ventricular Tachyarrhythmia
Sustained monomorphic VT was inducible in 38 patients (39%), whereas VF and nonsustained ventricular tachyarrhythmias were induced in 19 patients (20%) and in 40 patients (41%), respectively. Inducibility of VT was highest (32 of 58 [55%]) in those patients who presented with VT, only 17% (3 of 18) in patients with clinical VF, and 14% (3 of 21) in patients presenting with syncope. The incidence of inducible VF was higher in patients presenting with either VF (7 of 18 [39%]) or syncope (6 of 21 [29%]) compared with only 10% (6 of 58) of patients with clinical VT (P<.002).
Nonsustained ventricular tachyarrhythmias and VF, but in no case VT, were induced in 4 and in 1 of the 5 patients, respectively, who presented with VT while on treatment with class I antiarrhythmic drugs for atrial fibrillation (n=2) and frequent ventricular extrasystoles (n=3). After readministration of the drug on which a sustained ventricular tachyarrhythmia had occurred, sustained VT and/or VF were inducible. Therefore, in these patients the clinical arrhythmia (VT) was considered a proarrhythmic effect of the previous antiarrhythmic drug. Therefore, all of them were discharged without class I antiarrhythmic medication.
Presenting and Inducible Ventricular
Tachyarrhythmias in Relation to the Type of
Valvular Heart Disease
The inducibility of VT or VF differed considerably
(P<.001) between the subsets of patients on the basis of
the predominant hemodynamic consequence of their
valvular heart disease (Table 2). Induction of these
arrhythmias occurred in 3 of 14 patients (21%) with left
ventricular pressure overload, in 18 of 27 patients (67%)
with right ventricular pressure overload, in 24 of 37
patients (65%) with left ventricular volume overload, in 1
of 4 patients (25%) with right ventricular volume
overload, and in 11 of 15 patients (73%) with no significant pressure
or volume overload. Thus, VT/VF was inducible in 38 of 70 patients
(54%) with left-sided hemodynamic dysfunction versus
in 19 of 27 patients (70%) with right-sided dysfunction
(P<.05).
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Ejection Fraction in Relation to the Presenting and
Induced Arrhythmias
The mean left ventricular ejection fraction (n=75) was
59±18%. All patients with right-sided valvular heart disease
and the majority (80%) of patients with left-sided valvular
heart disease had an ejection fraction >40% (25 of 30 [83%]
without and 24 of 31 [77%] with prosthetic valve
replacement; NS). In detail, all patients with right
ventricular volume overload and 12 of 13 (92%) patients
with no significant pressure or volume overload had an ejection
fraction >40%. Furthermore, the majority of patients with left
ventricular pressure overload (10 of 12 [83%]), with
left ventricular volume overload (23 of 31 [74%]), and
with right ventricular pressure overload (16 of 17
[94%]) had also an ejection fraction >40%.
All patients with an ejection fraction 
40% presented with VT
or VF (Table 1
). In contrast, only 73% of the patients who had an
ejection fraction >40% presented with these
arrhythmias. As presented in Table 2, VT or VF could be
induced in 66% and in 54% of the patients with an ejection fraction
ejection fraction 40% and >40%, respectively (NS).
Therapy at Discharge
Fig 1 presents the type of therapy at hospital discharge as
well as the results of follow-up (51±39 months) for the three types of
inducible ventricular
tachyarrhythmias.
A total of 22 patients (23%; inducible nonsustained
ventricular tachyarrhythmias, n=17;
inducible VT, n=4; inducible VF, n=1) were discharged without
antiarrhythmic therapy (4 patients with assumed proarrhythmic effects
on antiarrhythmic drugs; 10 patients presenting with syncope and
with no inducible sustained ventricular
tachyarrhythmias; 8 patients with clinical VT). Three
of these 8 patients had suffered slow, hemodynamically
well-tolerated VT during the first 2 weeks after valve replacement and
had no inducible sustained ventricular
tachyarrhythmias. Five patients had spontaneous and
inducible VT (n=4) or VF (n=1) and refused any antiarrhythmic
treatment. Eleven patients were discharged on antiarrhythmic drugs
(class I, n=7; class III, n=4) that had not been serially tested
(inducible nonsustained ventricular
tachyarrhythmias, n=5; inducible VT, n=1; inducible VF,
n=5). Another 35 patients (36%; inducible nonsustained
ventricular tachyarrhythmias, n=4;
inducible VT, n=23; inducible VF, n=8) were discharged on
antiarrhythmic drugs (class I, n=9; class III, n=16; class I and class
III, n=10) after serial drug testing because of clinical VT (n=27), VF
(n=4), and syncope (n=4). The 4 patients with inducible nonsustained
ventricular tachyarrhythmias who underwent
serial drug testing had long episodes of nonsustained VT (15
seconds), had previously suffered spontaneous VT, and after
antiarrhythmic drugs only <4 ventricular echo beats were
inducible. With serial drug testing, the inducible arrhythmia
had been completely suppressed or it was more difficult to induce
(partially suppressed) in 18 patients (19%) and in 9 patients (9%),
respectively. Four patients were discharged on antiarrhythmic drugs
without significant changes in inducibility because they refused to
continue serial drug testing. Twenty-nine patients (30%) with clinical
VT (n=13), VF (n=13), or syncope (n=3) received an implantable
cardioverter-defibrillator because arrhythmias were still
inducible on antiarrhythmic drugs or because the clinically documented
arrhythmia was not inducible without antiarrhythmic drugs. In
addition, 9 patients who received an implantable
cardioverter-defibrillator were discharged on antiarrhythmic drugs
(class III, n=6; class I and class III, n=1; class IV, n=1; class III
and class IV, n=1) because of recurrent episodes of
ventricular tachyarrhythmias or because of
atrial fibrillation with fast ventricular rates.
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Follow-up
A complete follow-up was available in all patients. Seventeen
patients (18%) died during follow-up (heart failure, n=4; sudden
death, n=7; noncardiac causes, n=6). Two patients who died from cardiac
failure had left ventricular volume overload (with valve
replacement, n=1); two had right ventricular pressure
overload. Three of them had previously suffered a VT
recurrence. Two of the 6 patients who did not die of cardiac
causes had suffered VT recurrences. Sudden death occurred in 2
of 22 (9%) patients without antiarrhythmic therapy, in 1 of 11 (9%)
patients treated without serially tested antiarrhythmic drugs and in 2
of 35 patients (6%) treated with serially tested antiarrhythmic drugs
(respectively), and in 2 of 29 patients (7%) treated with an
implantable cardioverter-defibrillator. Furthermore, sudden death
occurred in 6 patients with left ventricular volume
overload and in 1 patient with left ventricular pressure
overload.
Fig 1 presents the follow-up data of arrhythmic events in detail.
Arrhythmic events (sudden death or VT/VF) occurred in a total of 40
patients (41%). At 1, 2, and 3 years, event-free survival for sudden
death, VT, or VF was 77%, 68%, and 61%, respectively.
Patients with inducible VT presented with a higher incidence of
arrhythmic events (24 of 38 [63%]; Figs 1 and 2) than those patients
with inducible nonsustained ventricular
tachyarrhythmias only (10 of 40 [25%]) or with
inducible VF (6 of 19 [32%])
(P<.002). One of
the 19 patients (5%) with inducible VF and only 1 of the 40 patients
(3%) with inducible nonsustained ventricular
tachyarrhythmias but 5 of the 38 patients (13%) with
inducible VT died suddenly during follow-up (inducible VT versus
others, P<.05).
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There was no relation between sex, the location of valvular
heart disease, the ejection fraction, or the presenting
arrhythmia with the incidence of arrhythmic events (Table 3). The incidence of
arrhythmic events varied with the hemodynamic type of
valve lesion. It occurred in 21 of 37 patients (57%) with left
ventricular volume overload, 6 of 15 patients (40%) with
no significant pressure or volume overload, 10 of 27 patients (37%)
with right ventricular pressure overload, but in 21% of
the patients with left ventricular pressure overload (n=14)
and never in patients with right ventricular volume
overload (this group included only 4 patients).
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Cox regression analysis showed that inducibility of VT and left
ventricular volume overload were significant predictors of
recurrence of arrhythmic events (P<.0003 and
P<.008, respectively) (Fig 2). Patients with (both)
inducible VT and left ventricular volume overload had an
incidence of arrhythmic events as high as 80%. In contrast, patients
with either inducible VT or left ventricular volume
overload (one of both) and patients without inducible VT and no left
ventricular volume overload had a much lower incidence of
recurrences (47% and 19%, respectively;
P<.0005).
Of those patients who were discharged after completion of antiarrhythmic serial drug testing, arrhythmic events occurred in 10 of 18 patients (56%) with complete suppression and in 5 of 9 patients (56%) of those patients with only partial suppression of inducibility. Overall (including patients with inducible VT/VF treated with an implantable cardioverter-defibrillator) incidence of arrhythmic events was 53% in patients without a change of inducibility using antiarrhythmic drugs. Thus, partial or total suppression of inducibility during serial drug testing did not improve prognosis in relation to the incidence of arrhythmic events.
In addition, 16 of 29 patients (55%) who received a cardioverter-defibrillator and 3 of 11 patients (27%) who were discharged with antiarrhythmic drugs that were not serially tested suffered arrhythmic events during follow-up. Two patients with implanted cardioverter-defibrillators died suddenly. Both had had previous arrhythmic events. Intraoperative and postoperative testing of the implanted devices had shown adequate sensing, pacing, and defibrillation thresholds.
Overall, sudden death occurred in 2 of 16 (13%) of patients treated with an implantable cardioverter-defibrillator, 2 of 16 patients treated with serially tested antiarrhythmic drugs, and in 1 of 3 patients treated with antiarrhythmic drugs not serially tested and in 2 of 3 patients without antiarrhythmic therapy who suffered arrhythmic events during follow-up.
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Discussion |
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The present study of patients with valvular heart disease presenting with a history of ventricular arrhythmias or syncope yields three important findings: (1) Results of programmed ventricular stimulation correlate with long-term follow-up. In patients with valvular heart disease in whom only VF was inducible (n=19), 1 sudden death (5%) occurred and 6 arrhythmic events occurred (32%). In patients in whom only nonsustained ventricular tachyarrhythmias were inducible (n=40), sudden death was rare (2.5%) but 25% of these patients suffered arrhythmic events. Patients with inducible monomorphic sustained VT represent a very high-risk group with a sudden death rate of 13% and recurrence of arrhythmic events in more than half of the patients (63%) (P<.002).
(2) Although spontaneous sustained ventricular tachyarrhythmias had been documented in the broad majority (78%) of patients, they were inducible in a very low percentage and, in addition, these patients demonstrated a poor prognosis despite therapy. Thus, serial drug testing seems not to be a useful method of treatment for the majority of these patients because a low percentage of patients have inducible ventricular tachyarrhythmias that could be used for serial drug testing and because the incidence of recurrence of arrhythmic events (sudden death, VT, or VF) is very high (56% in patients with complete or with partial suppression of inducibility). However, programmed ventricular stimulation might identify those patients at highest risk of suffering arrhythmic events during follow-up (despite therapy).
(3) In our cohort of patients there was a very high (41%) recurrence rate of arrhythmic events. This incidence was higher in patients with left-sided valvular disease (nonoperated, 48%; operated, 44%) than in patients with right-sided valvular disease (30%). Thus, inducibility and clinical outcome are influenced by the type of workload imposed on the (left) ventricle. Patients with left ventricular volume overload had the worse prognosis with the highest rate of recurrence of arrhythmic events (57%). In contrast, patients (n=14) with left ventricular pressure overload had the lowest incidence of inducible VT (14%) and fewer recurrences of arrhythmic events (21%) in these series. Although this group included only 14 patients and therefore the results might have been coincidental, the long follow-up (ranging from 6 to 160 months) of these patients makes this hypothesis improbable. As suggested by the results of Wolfe et al,8 von Olshausen et al,20 and Klein,21 it seems more probable that in this small subset of patients, left ventricular damage was less severe than in patients with left ventricular volume overload. Taking several previous reports into account3 8 20 21 22 as well as our data, it seems logical to consider all patients with valvular heart disease who present with sustained ventricular tachyarrhythmias as a population with a very high risk of recurrences. Sex, location of valvular heart disease, the type of presenting clinical arrhythmia, as well as left ventricular ejection fraction did not significantly influence outcome.
Comparison to Previous Data
Few data exist on the clinical utility of programmed
ventricular stimulation in assessment of the long-term
prognosis of patients with valvular heart disease after
spontaneous life-threatening ventricular
arrhythmias.19 Saxon and Denes19
reported that 12 patients with valvular heart disease and
inducible VT/VF had an improved 3-year survival (P<.05)
compared with 91 patients with coronary artery disease and
inducible VT/VF. However, these authors had included in their study 16
patients with valvular heart disease and 114 patients with
coronary artery disease and did not report on therapy and
outcome of those patients (of both groups) without inducible VT/VF or
those 91 patients with coronary artery disease who had
inducible VT/VF. In addition, their study19 did not report
the incidence of arrhythmic events (eg, the incidence of VT
recurrence) but only on probability of survival (91% in the
valvular group and 55% in the coronary artery disease
group). Although they used a more aggressive stimulation protocol, as
we did (they included quadruple extrastimuli and left
ventricular stimulation after coupled or burst pacing),
they could induce VT/VF in only 12 of the 16 patients (75%) with
valvular heart disease. Thus, despite several differences
between their study and ours (eg, number of patients, type, location of
valvular heart disease, stimulation protocol, and follow-up
data), some similarities exist. In both studies, the induction rate of
sustained ventricular tachyarrhythmias was
similar (50% and 59%) with the use of triple extrastimuli. In our
study, 11 patients (11%) died from cardiac causes (sudden cardiac
death, n=7; heart failure, n=4), which is somewhat higher than the
mortality rate (9%) presented by these authors.
Only few recent and nonbiased data on the natural history of valvular heart disease exist.6 7 8 23 Recently, Wolfe et al8 reported that 25 of 462 patients (5.4%) with aortic stenosis and 3 of 592 patients (0.5%) with pulmonary stenosis, who were participants in the First Natural History Study (NHS-1), died suddenly. Horstkotte7 reported that the linearized incidence of sudden death events per year was 0.33 in patients with moderate mitral stenosis, 0.45 in patients with significant mitral stenosis, and 5.77 in patients in whom surgery is indicated but refused mitral valve replacement. The late (median follow-up, 184 months) postoperative linearized incidence of sudden death per year in patients who underwent mitral and aortic valve replacement was 0.50 and 0.52, respectively.7 In addition, Delahaye et al6 observed that 4 of 32 patients with moderate mitral regurgitation and 4 of 160 patients with severe mitral regurgitation scheduled for valve replacement died suddenly before surgery.
Previous studies with Holter monitoring in patients with aortic valve
disease have demonstrated that the occurrence of
ventricular arrhythmias was not correlated to the
type of valve lesion (stenosis, regurgitation,
or combined stenosis and regurgitation), to the
transvalvular gradient or to the degree of
regurgitation,20 21 or to the absence or
presence of concomitant coronary artery disease.21
However, spontaneous ventricular arrhythmias (VT
was defined as 3 ventricular premature beats with a
frequency >100/min) occurred in 18% of the patients. They were
strongly influenced by the presence of impaired left
ventricular function.20 Similar results were
presented by Meinertz et al24 using Holter
monitoring in patients with aortic and/or mitral valve disease. The
results of these studies suggest that increased myocardial mass,
ventricular dilatation, and ventricular wall
stress might influence the occurrence of spontaneous complex
ventricular tachyarrhythmias, which have
been associated with the development of sustained
ventricular tachyarrhythmias and sudden
cardiac death.1 2 3 20 21 24
Gohlke-Bärwolf et al25 reported that prognosis of
patients with pure severe aortic stenosis (n=234) was excellent
after aortic valve replacement (5-year survival rate, 93%) and was
similar to that of the age-adjusted general population. These authors
reported that 30% and 38% of the patients had Lown grade 4 to 5 on
Holter monitoring before and after surgery, respectively. These
patients received antiarrhythmic drugs. However, the authors did not
specify which drugs were given and if serial drug testing had been
used. The results of Wolfe et al8 suggest that the
propensity to serious arrhythmic events may not be correlated merely to
the present hemodynamic state but rather to the
state of the ventricles over time. Patients with mild aortic
stenosis (not requiring surgery) had nonsustained VT (3
ventricular premature beats) as rarely as the normal
population (2%) but it was higher in patients who had to be treated
with valvulotomy (10%) or with aortic valve replacement (14%). In
contrast, this arrhythmia occurred in 7.7% and in 3.6% of
patients with pulmonary stenosis who were medically or
surgically treated, respectively.8
Mitral valve prolapse is the most common valvular abnormality in American adults.4 5 Although the incidence of lethal ventricular arrhythmias is very low (possibly <0.01%),4 5 patients with documented VT and fibrillation are at high risk of recurrence despite antiarrhythmic drug therapy.26 In addition, the prognosis of these patients appears to be more related to the presenting symptoms than to the response to programmed ventricular stimulation.26 Naccarelli et al27 reported the results of programmed ventricular stimulation of 18 patients with mitral valve prolapse who presented with sustained VT (n=5, 28%) or with nonsustained VT (n=13, 72%). Sustained VT could only be induced in 3 of the 5 patients who presented with these arrhythmias, whereas nonsustained VT was inducible in another 7 patients. Similar results were presented by other investigators.9 26 In addition, Vohra et al9 reported on the high risk of sudden death and of malignant ventricular arrhythmias in a selected subset of patients with mitral valve prolapse (all with trivial to mild mitral regurgitation and normal left ventricular function) who presented with presyncope, syncope, or cardiac arrest.
Possible Mechanisms of Ventricular Arrhythmias,
Syncope, and Sudden Death in Patients With Valvular Heart
Disease
Patients with chronic pressure overload and
hypertrophy of the left ventricle have increased
ventricular wall stress,28 reduced blood flow
per unit mass of myocardium,29 subendocardial
ischemia despite normal coronary
arteries,30 31 and reduced capillary density per
myocardial mass.32 33 Similar factors might be operative
in abnormalities of right-sided valves. In addition,
hemodynamic changes could be induced by stimulation of
left ventricular baroreceptors, which can lead to
arterial hypotension, a fall in venous return, and
bradycardia.34 35 36 37 Furthermore, inappropriate hypotension
and low cardiac output might lead to myocardial ischemia and
lethal rhythm disorders. Conduction disturbances with AV block
could also explain syncope and sudden death in some of these
patients.23 37
In patients with volume overload, the previously mentioned mechanisms and additional mechanical distension of myocardial fibers could enhance the probability of developing malignant arrhythmias, as might do different drugs for therapy.38 39 Chronic volume overload leads to macroscopic and microscopic changes in the structure of the myocardium with loss of connections between cell bundles and appearance of fibrotic tissue separating bundles. Such changes would lead to nonuniformities in electrical wave propagation and would set the stage for sustained reentrant activity. Furthermore, the results of previous studies, which indicate that greater increases in left ventricular volume relative to ventricular mass might result in inadequate hypertrophy associated with elevation in wall stress and of myocardial oxygen requirements29 as well as decreased myocardial contractility,40 may explain the worse outcome of patients with left ventricular volume overload compared with left ventricular pressure overload in this series. In addition, adrenergic activity and rapid heart rate as a consequence of hemodynamic dysfunction may be an arrhythmogenic factor.41
Stretch may cause several arrhythmogenic mechanisms (enhanced normal automaticity in Purkinje fibers, abnormal automaticity, and triggered activity based on early or delayed after-depolarizations in Purkinje and muscle fibers).41 42 This mechanism may occur in patients with mitral valve prolapse but also in other valvular disorders. Furthermore, enhanced adrenergic activity and hyperresponsiveness to catecholamines have been reported in patients with mitral valve prolapse.43
In patients who underwent surgery for right- or left-sided valvular heart disease, ventricular arrhythmias might occur as a consequence of long-term myocardial damage and consecutive fibrosis. In addition, after valve replacement, bleeding, endocarditis, systemic embolization, valve obstruction, or regurgitation might cause death in these patients, which in most cases is unwitnessed but not sudden.44 45 46
Thus there are several possible mechanisms of arrhythmia in the setting of valvular heart disease. It is not possible to identify a single, dominant mechanism in either the whole population or in an individual patient. It might be hypothesized that other not-yet-known mechanisms of arrhythmogenesis could also play a role in patients without significant pressure or volume overload.
Limitations
This was a retrospective study. Outcome was analyzed in
relation to clinical characteristics, presenting
arrhythmias, and induced arrhythmias, and therapy was
guided by these variables. This study includes patients who were
referred to our institution over a long time (1985 to 1994). Because
therapeutic regimen has changed significantly over time (eg, ACE
inhibitors, introduction of the transvenous implantable
cardioverter-defibrillators), no comparison of therapies is possible.
Subgroups of different types of valvular heart disease are too
small to exclude minor but important changes. Therefore, studies of
patients were performed on the basis of clinical approaches (eg,
location and hemodynamic dysfunction of
valvular heart disease and inducible arrhythmia) for
the analysis. Other stimulation protocols, other antiarrhythmic
drugs, or other dosages could have led to other results. A 12-lead ECG
documentation of VT episodes could not be obtained in the majority of
patients. Therefore, a correlation of VT morphologies with the type of
valvular heart disease was not possible.
Conclusions
The results of this study indicate that the overall inducibility
of sustained ventricular tachyarrhythmias
in this patient group is low and that the recurrence rate of
arrhythmic events is very high despite therapy. Patients with
valvular heart disease presenting with sustained
ventricular tachyarrhythmias should
therefore be considered a very high-risk population. Those patients
with inducible sustained VT and left ventricular volume
overload are at highest risk of recurring arrhythmic events. Serial
drug testing has little value in the managing of patients with
valvular heart disease and history of sustained
ventricular tachyarrhythmias. Therefore,
nonpharmacological procedures, especially the implantation of automatic
cardioverter-defibrillators, should be strongly considered in the
management of all these patients.
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Acknowledgments |
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This study was supported in part by the Franz Loogen Foundation, Düsseldorf, Germany. The data for this study are partly based on the doctoral thesis prepared by Yvonne Schwammenthal, MD.
Received September 30, 1996; revision received February 7, 1997; accepted February 11, 1997.
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