Can arrhythmias lead to heart failure

Arrhythmia Induced Cardiomyopathy

Background: Heart failure affects around 1–2% of the population and is associated with increased morbidity and mortality. Cardiac arrhythmias often occur secondary, but can also be the cause of left ventricular systolic dysfunction (LVSD) in the sense of arrhythmia-induced cardiomyopathy (AIC). This causal relationship must be taken into account when treating patients with systolic heart failure and arrhythmias.

Method: A selective literature search was carried out in PubMed (1987–2017) taking into account the current guideline recommendations.

Results: The key criterion for diagnosing AIC is evidence of persistent arrhythmia (or pathological tachycardia) in connection with LVSD that cannot be explained otherwise. Almost every tachycardiac arrhythmia and frequent ventricular extrasystoles can lead to progressive LVSD if they persist. The mechanisms are not fully understood; In addition to the increase in the ventricular frequency, an asynchronous cardiac contraction process and neurohumoral activation are obviously pathophysiologically significant. The most common triggers are supraventricular tachycardias in children and atrial fibrillation in adults. Current studies indicate that the causal importance of atrial fibrillation is underestimated when LVSD is otherwise inexplicable. The therapy of an AIC consists primarily in the treatment of the arrhythmia. Medicines such as beta blockers and amiodarone can be used for this; Depending on the type of arrhythmia, catheter ablation should be considered individually as a long-term therapy. The diagnosis of AIC is considered confirmed if the LVSD normalizes or improves within a few weeks to months through targeted treatment of the arrhythmia.

Conclusion: Since AIC is potentially reversible, recognition of the clinical picture and adequate treatment of the underlying arrhythmia are prognostically important.

Heart failure is a leading cause of morbidity and mortality in Western nations. In the general population, around 1–2% of adults and> 10% of those over 70 years of age are affected (1–3). Together with the continuously aging population, heart failure represents one of the great challenges for modern medicine and health economics.

In the diagnostic algorithm of systolic heart failure, the identification of the underlying cause of a ventricular pump dysfunction is of paramount importance for initiating causal therapy and assessing the prognosis (4).

Arrhythmia-induced cardiomyopathy (also tachymyopathy or tachycardia-induced cardiomyopathy) is a subtype of (non-familial) dilated cardiomyopathy (5, 6). It is characterized by left ventricular systolic dysfunction (LVSD), which is causally caused by high and / or irregular ventricular frequencies and can be cured through elimination or effective treatment of the underlying arrhythmia (7). In the classical form, the arrhythmia is the sole substrate and the LVSD is completely reversible. Arrhythmia-induced cardiomyopathy can, however, aggravate LVSD even with pre-existing structural heart disease and is then only partially reversible (8, 9).

Arrhythmia-induced cardiomyopathy can apparently occur at any age. Although the clinical picture has been known for decades (10) and has been well characterized by animal models, there are hardly any prospectively collected clinical or reliable epidemiological data and the prevalence is ultimately unclear.

In more recent therapy studies, it is noticeable that about a third of the patients included with atrial fibrillation and systolic heart failure have primarily idiopathic LVSD and that in 58–88% of these cases arrhythmia-induced cardiomyopathy or a relevant component of this disease can be demonstrated (11, 12). In a cohort study of 1,269 consecutive patients with atrial flutter, arrhythmia-induced cardiomyopathy was diagnosed in 56% of the cases (103/184) of the LVSD subgroup after ablation of the arrhythmia (13). In contrast, the importance of arrhythmia-induced cardiomyopathy is likely to be underestimated in clinical practice when arrhythmia is considered solely as a consequence and not as a possible cause of cardiomyopathy.

methodology

The literature was selectively researched in PubMed from 1987–2017 on the basis of the authors' clinical and scientific experience. The detailed description can be found in the eMethods section.

Pathophysiology

Persistent tachycardia reproducibly induces systolic heart failure in various animal models (Figure 1) with a typical cellular heart failure phenotype (14–16). A decrease in systolic contractility with consecutively decreased cardiac output, increased wall tension, and dilatation of the heart cavities can be observed within days to weeks (15, 17). In the further course (depending on the model, usually after a few weeks), the persistent tachycardia and excessive neurohumoral activation develop into the complete cardiac insufficiency phenotype with marked LVSD and dilatation of the heart cavities (8, 15, 17–20). If the tachycardiac stimulation is stopped, the described changes normalize within days to weeks in the animal model and within weeks to months in humans (Figure 1) (21).

In the animal model, the extent of LVSD increases with the heart rate and the duration of the tachycardia (22). In addition, other factors seem to influence the pathological sequence of arrhythmia-induced cardiomyopathy. LVSD progresses faster and is more pronounced when the tachycardiac stimulation does not come from the atria but from the ventricles (8, 23). The dyssynchronous electrical excitation of the heart resulting from the ventricular stimulation (loss of the physiological AV sequence and the synchronous ventricular activation) apparently potentiates the effect of tachycardia as a cofactor.

The functional and molecular effects of a long-lasting tachycardia on the myocardium and the development of heart failure have been examined almost exclusively in animal models and may therefore only be transferable to humans to a limited extent.

General diagnosis and therapy

The key diagnostic criterion for arrhythmia-induced cardiomyopathy is evidence of persistent arrhythmia or pathological tachycardia in connection with LVSD that cannot be explained otherwise. Various arrhythmias can lead to arrhythmia-induced cardiomyopathy (box) (8). The duration of the arrhythmia and the level of the heart rate are important factors, but there are no threshold values ​​for this (8). A significant arrhythmia cannot always be diagnosed with a single 12-lead ECG. A long-term ECG can be used to determine, for example, recurrent tachycardias, the mean ventricular frequency in atrial fibrillation or the frequency of ventricular extrasystoles.

The causal connection between arrhythmia and LVSD is often difficult to assess at first, as any form of LVSD can in principle also lead to arrhythmias (“chicken and egg” question). The possible diagnostic procedure for suspected arrhythmia-induced cardiomyopathy is summarized in Figure 2. After the basic diagnosis has been carried out, potential causes must be ruled out through targeted special diagnosis. Clinical studies have shown that the extent of initial left ventricular dilation in patients with arrhythmia-induced cardiomyopathy is less than in those with dilated cardiomyopathy and secondary tachycardia (24, 25). In a retrospective analysis, an end-diastolic diameter of the left ventricle (LV) ≤ 61 mm with a sensitivity of 100% and a specificity of 71% predicted arrhythmia-induced cardiomyopathy (24).

In addition, several studies indicate the potential of magnetic resonance imaging (MRI) in the diagnosis of arrhythmia-induced cardiomyopathy (8, 11, 26–28). Accordingly, if the cardiomyopathy is unclear, the lack of ventricular "Late Gadolinium Enhancement" (LGE) distinguishes the arrhythmia-induced cardiomyopathy from other heart diseases. In the LGE, images are acquired using magnetic resonance approximately 15 minutes after the administration of gadolinium-containing contrast medium and necrosis, scar areas and myocardial fibrosis are visualized as contrast-enhancing, hyperintense areas. For the differential diagnosis between cardiomyopathy and inflammatory heart disease, magnetic resonance imaging is considered to be superior to other methods (29) and, in our opinion, can be recommended for the diagnosis of arrhythmia-induced cardiomyopathy.

The myocardial biopsies of patients with arrhythmia-induced cardiomyopathy and cardiomyopathy of other origins (dilated or inflammatory) were recently compared histopathologically (30). The arrhythmia-induced cardiomyopathy was characterized, among other things, by a lack of or only slight myocardial fibrosis, increased expression of "major histocompatibility complex" class II molecules and infiltration with CD68 + macrophages. The potential role of myocardial biopsy in the diagnosis of arrhythmia-induced cardiomyopathy, however, requires additional prospective studies.

The diagnosis of arrhythmia-induced cardiomyopathy is currently considered confirmed if the LVSD is completely reversible within a few weeks to months after successful treatment of the arrhythmia (or partially) in the case of pre-existing structural heart disease (8).

The therapy of arrhythmia-induced cardiomyopathy focuses on the treatment of the arrhythmia, primarily by eliminating the arrhythmia, alternatively - for example in the case of permanent atrial fibrillation - by controlling the ventricular rate (8, 31–38). The spectrum of drugs that can be used to treat arrhythmias is essentially reduced to beta blockers, digitalis preparations and amiodarone in LVSD. Other antiarrhythmics may only be used after carefully weighing the risks and benefits. Depending on the patient's age, comorbidity and rhythm disturbance, catheter ablation is usually the therapy of choice in the long term.

In addition to causal “rhythm therapy”, arrhythmia-induced cardiomyopathy is treated with the medication generally recommended for systolic heart failure (Figure 3) (1, 4). It should be mentioned, however, that no specific study data exist for arrhythmia-induced cardiomyopathy, which prove the favorable influence of this heart failure medication on the course or prognosis. This also applies to drug administration after the left ventricular pump function has recovered. Even taking into account the existing knowledge on the pathophysiology of arrhythmia-induced cardiomyopathy, heart failure medication still appears to be indicated, not least because the importance of this therapy for systolic heart failure in general (regardless of the etiology) is proven at a high level of evidence and anchored in the guidelines (1 , 4). Figure 3 summarizes the general therapy principles for arrhythmia-induced cardiomyopathy.

Since arrhythmia-induced cardiomyopathy is a reversible form of cardiomyopathy, primary prophylactic implantation of a defibrillator is not indicated, even if LVSD is initially severe (39). The transient use of a defibrillator vest can be considered as a bridging treatment option in patients with suspected arrhythmia-induced cardiomyopathy (40).

Arrhythmia-specific diagnostics and therapy

Atrial fibrillation

In adults, atrial fibrillation is the most common persistent arrhythmia and the most common cause of arrhythmia-induced cardiomyopathy (24, e1). LVSD is found in 20–30% of all patients with atrial fibrillation (e2), and 10–50% of patients with heart failure have atrial fibrillation (e3). Structural heart disease is often present in atrial fibrillation and LVSD. However, 25–50% of those affected probably have at least one component of arrhythmia-induced cardiomyopathy (8, 11, e4). It should be emphasized that arrhythmia-induced cardiomyopathy can also occur with atrial fibrillation and normal ventricular frequencies (11).

In clinical practice, it is not uncommon for atrial fibrillation and LVSD to be diagnosed for the first time at the same time, so that the causal relationship is initially unclear. In these cases, drug frequency control (beta blockers ± digitalis) and drug therapy for heart failure should be sought first (e2), since at the time of initial contact it can also be atrial fibrillation due to heart failure. Which ventricular frequencies are ideal has not been conclusively clarified. We currently recommend 60–100 rpm in rest and < 110 in="" bei="" leichter="" belastung="" (1).="" insbesondere="" bei="" anhaltender="" symptomatik,="" unzureichender="" frequenzkontrolle="" und/oder="" fortbestehender="" lvsd="" folgt="" (sofern="" keine="" kontraindikationen="" vorliegen)="" ein="" rhythmisierungsversuch="" mittels="" elektrischer="" kardioversion="" und="" gegebenenfalls="" amiodaron.="" verlaufsabhängig="" und="" unter="" berücksichtigung="" der="" weiteren="" diagnostik="" (grafik="" 2)="" kann="" dann="" differenziert="" werden,="" ob="" der="">

  • a pure arrhythmia-induced cardiomyopathy (due to atrial fibrillation),
  • another heart disease (resulting in atrial fibrillation) or
  • a mixed form (other heart disease and worsening of the LVSD due to atrial fibrillation)

underlying.

The majority of randomized studies on the treatment of atrial fibrillation in LVSD included predominantly patients with chronic systolic heart failure and structural heart disease. In this case, rhythmization with electrical cardioversion and amiodarone led to an improvement in left ventricular pump function and quality of life (e5), but not to a reduction in mortality (e6). In a meta-analysis (26 studies, 1,838 patients with LVSD, 61% structural heart disease, 39% idiopathic), the mean left ventricular ejection fraction improved from 40% to 53% after left atrial ablation of atrial fibrillation (e7). This positive effect was also found in an earlier observational study in structural heart disease, but less pronounced than in primary idiopathic LVSD (increase in left ventricular ejection fraction by 16 ± 14% and 24 ± 10%) (12).

Only a few prospective studies have specifically investigated the influence of catheter ablation in atrial fibrillation in patients with primarily idiopathic LVSD (and thus most likely pure arrhythmia-induced cardiomyopathy). In a study on 16 patients, the left ventricular pump function normalized in the 15 participants with stable sinus rhythm (ejection fraction 40 ± 10% at inclusion and 60 ± 6% after 6 months, p < 0,001) (27).="" eine="" randomisierte="" studie="" an="" 68="" patienten="" mit="" primär="" idiopathischer="" lvsd="" konnte="" jüngst="" zeigen,="" dass="" auch="" bei="" zuvor="" optimaler="" medikamentöser="" frequenzkontrolle="" die="" ablation="" von="" vorhofflimmern="" die="" linksventrikuläre="" ejektionsfraktion="" (32 ± 9 %="" auf="" 50 ± 11 %="" versus="" 34 ± 8 %="" auf="" 38 ± 9 %="" bei="" fortgeführter="" frequenzkontrolle,="" p="">< 0,0001) deutlich="" bessert="" (11).="" war="" in="" einer="" vorausgehenden="" untersuchung="" mithilfe="" der="" magnetresonanztomographie="" kein="" ventrikuläres="" lge="" nachweisbar,="" normalisierte="" sich="" die="" linksventrikuläre="" ejektionsfraktion="" bei="" drei="" viertel="" der="" patienten="" nach="">

In summary, in arrhythmia-induced cardiomyopathy due to atrial fibrillation, preservation of the sinus rhythm should be sought. Catheter ablation in the left atrium should be considered as therapy, taking into account the patient's age, comorbidity, symptoms, and wishes (e2). The risk of a relevant procedural complication is around 5%, and in around half of the cases more than one procedure is required to stabilize the sinus rhythm (e2). In the case of therapy-refractory, recurrent or permanent atrial fibrillation with a ventricular frequency that cannot be adequately controlled with medication, the combination of AV node ablation and (possibly bi-) ventricular stimulation ("ablate and pace") is ultimately a safe and effective treatment option (e2, e8, e9).

Atrial flutter

In an analysis of> 1,000 patients with atrial flutter, the frequency of arrhythmia-induced cardiomyopathy was around 8% (13). In arrhythmia-induced cardiomyopathy, those affected had higher ventricular frequencies during atrial flutter (109 ± 19 versus 84 ± 23 / min) than in LVSD of other origins (e10). The medical control of the ventricular rate is more difficult with atrial flutter than with atrial fibrillation, so that rhythmization is required more often. Electrical cardioversion is an effective measure for the acute restoration of sinus rhythm. In view of the risk of recurrence, however, catheter ablation should be considered, which is associated with high success rates and low complication rates in typical atrial flutter (e11). In patients with atrial flutter and LVSD, an improvement was found in over half of these cases and complete normalization of the left ventricular pump function in three quarters of these cases (13, e10).

Supraventricular tachycardias

The arrhythmias that belong to the group of supraventricular tachycardias (SVT) in the narrower sense are listed in the box. In adulthood, SVT are rarely the cause of arrhythmia-induced cardiomyopathy. In childhood, however, according to a multicenter study of 81 children, around 90% of cases of arrhythmia-induced cardiomyopathy are based on persistent SVT (e12). In this analysis, permanent focal atrial tachycardias were found in 59% of children with arrhythmia-induced cardiomyopathy and permanent junctional reentry tachycardias in 23%. These forms of tachycardia are rather rare in adulthood and relatively often (in 18–28% of cases) (8) lead to arrhythmia-induced cardiomyopathy in affected children, presumably because the sustained but relatively moderate increase in heart rate to 150–200 / min is common does not lead to acute symptoms (e13).

For the acute treatment of SVT, vagus maneuvers or the rapid intravenous administration of adenosine are primarily recommended (e11, e14). In the case of SVT-related arrhythmia-induced cardiomyopathy, however, this usually enables the SVT to be terminated transiently at best. If possible, catheter ablation should be sought as a curative therapy (e11, e14). The success rates vary between 80% and 95% depending on the SVT mechanism (e11, e14). In newborns and young children, ablation is only recommended if drug treatment is not possible or unsuccessful (e14).

Frequent ventricular extrasystoles and ventricular tachycardias

Frequent ventricular extrasystoles (VES) can result in arrhythmia-induced cardiomyopathy in patients without structural heart disease (33) and worsen left ventricular function in patients with pre-existing LVSD (e15, e16). In a study on patients with relatively frequent idiopathic ventricular extrasystoles (> 1,000 / day), arrhythmia-induced cardiomyopathy developed in 13 of the 239 patients (5.4%) during a follow-up period of 5.6 years (e17). The likelihood of arrhythmia-induced cardiomyopathy increases with the frequency of ventricular extrasystoles (e17). This is quantified in the long-term ECG as an absolute (ventricular extrasystoles / day) or relative frequency (ventricular extrasystoles load as a percentage of all QRS complexes). In the literature, threshold values ​​for the ventricular extrasystole load and the risk of arrhythmia-induced cardiomyopathy are given that vary from> 10% to> 24% ventricular extrasystoles (38, 39). The likelihood of arrhythmia-induced cardiomyopathy also increases with the QRS width of the ventricular extrasystoles, which correlates with the extent of the ventricular asynchrony (e18). According to retrospective analyzes, there is an increased risk of arrhythmia-induced cardiomyopathy if the ventricular extrasystole QRS width is> 150 ms (e18 – e20). If there is frequent ventricular extrasystoles and a corresponding risk, the left ventricular pump function should be checked regularly (6 to 12 months at our discretion) to rule out arrhythmia-induced cardiomyopathy (e17, e21).

Ventricular tachycardias are only rarely the cause of arrhythmia-induced cardiomyopathy, probably because they usually lead to acute symptoms and thus to therapy.

Catheter ablation is the treatment of choice for eliminating arrhythmia-induced cardiomyopathy-causing ventricular extrasystoles, with long-term success rates between 66% and 90% (e22, e23). Alternatively, depending on age, comorbidity, and the presumed focus of the ventricular extrasystoles, drug treatment, primarily with amiodarone, can be considered (e24).

Course and prognosis

After effective treatment, the left ventricular pump function normally recovers within a few weeks to months (8, 33, 36, e1, e25, e26). At our discretion, outpatient follow-up checks should initially be carried out closely (e.g. 1 to 3 months) and include both a (long-term) ECG and an echocardiogram. Depending on the triggering arrhythmia, arrhythmia recurrences with a frequency of around 5% (SVT) to around 50% (atrial fibrillation) can occur following successful catheter ablation (e2, e11). These can lead to the LV pump function not fully recovering during follow-up (e27) or rapidly deteriorating again after initial normalization (e1). The recurrence rate of arrhythmia-induced cardiomyopathy after successful therapy has not been conclusively clarified; in a study with 12 patients (observation period 53 ± 24 months) it is reported to be around 25% (e25).

If the left ventricular pumping function recovers with treatment of the arrhythmia, the prognosis for those affected is good as far as survival is concerned (13, e1, e25, e28). It should be noted, however, that in a study years after arrhythmia-induced cardiomyopathy and normalization of the LVSD, a slight left ventricular dilatation and ultrastructural changes in the myocardium were still detectable in the examination using magnetic resonance imaging (e29). This observation may also explain the apparently very rare but described cases of sudden cardiac death that have been observed in patients with arrhythmia-induced cardiomyopathy and already normalized left ventricular pump function (e1). The temporary continuation of heart failure medication after recovery of the LVSD therefore appears advisable, even if there is no evidence in this regard for arrhythmia-induced cardiomyopathy (8).

Conflict of interest
Prof. Sossalla has received reimbursement of travel and accommodation expenses from Berlin Chemie, Menarini, Novartis, Bayer, Böhringer Medtronic and Servier. He has received lecture fees from Novartis, Menarini, and Berlin-Chemie. He received funding from Novartis for a research project he initiated.

Prof. Vollmann has received reimbursement of conference attendance fees from Boston Scientific, Medtronic, and St. Jude Medical. He has received reimbursement for travel and accommodation from Biosense Webster, Boston Scientific, Medtronic, and St. Jude Medical. He has received honoraria for lecturing from Medtronic, St. Jude Medical, Böhringer Ingelheim, and Novartis.

Manuscript dates
submitted: October 1, 2017, revised version accepted: February 22, 2018

Address for the authors
Prof. Dr. med. Samuel Sossalla
Clinic and Polyclinic for Internal Medicine II
University Hospital Regensburg
Franz-Josef-Strauss-Allee 11, 93053 Regensburg
[email protected]

How to quote
Sossalla S, Vollmann D: Arrhythmia-induced cardiomyopathy — causes, clinical significance, and treatment. Dtsch Arztebl Int 2018; 115: 335-41.
DOI: 10.3238 / arztebl.2018.0335

► The German version of this article is available online:
www.aerzteblatt-international.de

Additional material
Literature marked with "e":
www.aerzteblatt.de/lit1918 or via QR code

eMethods part:
www.aerzteblatt.de/18m0335 or via QR code

Ponikowski P, Voors AA, Anker SD, et al .: 2016 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart failure of the European Society of Cardiology (ESC ). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail 2016; 18: 891-975 CrossRefMEDLINE
van Riet EE, Hoes AW, Limburg A, Landman MA, van der Hoeven H, Rutten FH: Prevalence of unrecognized heart failure in older persons with shortness of breath on exertion. Eur J Heart Fail 2014; 16: 772-7. CrossRefMEDLINE
Redfield MM, Jacobsen SJ, Burnett JC, Mahoney DW, Bailey KR, Rodeheffer RJ: Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA 2003; 289: 194-202 Cross Ref
German Medical Association (BÄK), KBK, Working Group of Scientific Medical Societies (AWMF): National Care Guideline for Chronic Heart Failure - Long Version. 2nd edition, Version 1 2017. DOI: 106101 / AZQ / 000386 2017.
Santangeli P, Marzo F, Camporeale A, Bellocci F, Crea F, Pieroni M: What do tachycardiomyopathy belong to? Eur Heart J 2008; 29: 1073-4 CrossRefMEDLINE
Pinto YM, Elliott PM, Arbustini E, et al .: Proposal for a revised definition of dilated cardiomyopathy, hypokinetic non-dilated cardiomyopathy, and its implications for clinical practice: a position statement of the ESC Working Group on Myocardial and Pericardial Diseases. Eur Heart J 2016; 37: 1850-8 CrossRefMEDLINE
Shinbane JS, Wood MA, Jensen DN, Ellenbogen KA, Fitzpatrick AP, Scheinman MM: Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol 1997; 29: 709-15 Cross Ref
Gopinathannair R, Etheridge SP, Marchlinski FE, Spinale FG, Lakkireddy D, Olshansky B: Arrhythmia-induced cardiomyopathies: mechanisms, recognition, and management. J Am Coll Cardiol 2015; 66: 1714-28 CrossRefMEDLINE PubMed Central
Fenelon G, Wijns W, Andries E, Brugada P: Tachycardiomyopathy: mechanisms and clinical implications. Pacing Clin Electrophysiol 1996; 19: 95-106 Cross Ref
Brill IC: Auricular fibrillation with congestive failure and no other evidence of organic heart disease. Am Heart J 1937: 175-82 CrossRef