M.Birhan YILMAZ, MD, FESCAssociate Professor of Cardiology,

Cumhuriyet University School of MedicineDepartment of Cardiology

Sivas, TURKEYSECOND ITALIAN GREAT NETWORK CONGRESS

October 18-21 2011Aula Urbani, Ospedale Sant’Andrea - Roma, Italy

M.Birhan YILMAZ, MD, FESCAssociate Professor of Cardiology,

Cumhuriyet University School of MedicineDepartment of Cardiology

Sivas, TURKEYSECOND ITALIAN GREAT NETWORK CONGRESS

October 18-21 2011Aula Urbani, Ospedale Sant’Andrea - Roma, Italy

Acute Heart Failure and Atrial Fibrillation

Acute Heart Failure and Atrial Fibrillation

Atrial fibrillation (AF) is a common rhythm in patients with acute heart failure (AHF).

Registry and trial data indicate that 20% to 35% of patients with AHF who are admitted to the hospital will be in AF at presentation.

In about one third of these patients, the AF will be of recent onset.

Asirvatham and Friedman. From: Shivkumar, Weiss, Fonarow, and Narula; eds. Braunwald’s Atlas of EP in HF. 2005.

Paroxysmal AF

Persistent AF

Permanent AF

Triggersectopic foci

ElectrophysiologicRemodeling

Chronic Substratefibrosis

Nattel et al. Circulation 1999;100:87-95

Types of AF

AF-HF interaction

Loss of atrial kick Rapid rate İrregular beat

Sympathetic

toneremodelling

Atrial

stretch

SOLVD Investigators: J Am Coll Cardiol. 1998;32:695-703.

Key Questions to Consider Before Starting Therapy

Does the patient have an ICD or pacemaker in place?

Does the patient have preserved or reduced systolic function at their baseline?

What is the duration of the AF episode? Is the patient already on drugs for rhythm or

rate control and anticoagulation? What concomitant disorders are present?

Types of AF in AHF

1-Acute symptomatic AF 2-Incessant AF 3-Acute on chronic AF

Acute symptomatic de novo AF

Either the AF episode itself has rapidly precipitated heart failure in a previously stable patient or worsening heart failure has triggered an acute episode of AF.

In these patients, the potential for successful early restoration of sinus rhythm is high if the heart failure symptoms can be controlled

Cardiomyopathy can be caused by any tachycardia (>110 bpm) that occurs as little as 10-15% of day

Severity related to rate and duration of HR Maximal improvement after rate control may

require up to 8 months After improvement susceptibility to rapid

deterioration remains if tachycardia recurs

Olshansky et al Circulation 2004, Fenelon et al PACE 1996;19:95-106,

Shinbane J et al. JACC 1997;29: 709-715

Atrial Fibrillation and Tachycardia

Induced Cardiomyopathy

Incessant AF

May be subacute or acute Depending on caardiac reserve, patients

become symptomatic During the ensuing days and weeks, the

patient gradually slips into ADHF and then presents with severe symptoms.

These patients will probably not convert spontaneously but may be candidates for a later cardioversion attempt.

Acute on chronic AF

Some patients with permanent AF that is usually well rate controlled will develop progressive heart failure and then present emergently with rapid ventricular rates due to the stress of the episode

Unlikely to control the rhythm

Patients with AF and signs of acute heart failure require urgent rate control and often cardioversion.

An urgent echocardiogram should be performed in haemodynamically compromised patients to assess LV and valvular function and right ventricular pressure.

The Atrial Fibrillation and Congestive Heart Failure (AF-CHF) trial observed no difference in cardiovascular mortality (primary outcome) between patients with an LVEF ≤35%, symptoms of congestive heart failure, and a history of AF randomized to rate or rhythm control, or in the secondary outcomes including death from any cause and worsening of heart failure

In the general population of patients with atrial fibrillation (AF), the main goals of therapy are the control of symptoms and the prevention of arterial embolism, particularly stroke. These goals are also true for the relatively large subset of AF patients with heart failure (HF).

In such patients, the adverse hemodynamic consequences of AF can quickly lead to a decrease in exercise capacity and a worsening of symptoms, both of which may be difficult to manage

In an analysis from the Framingham Heart Study, of 708 patients with heart failure (HF) who were in sinus rhythm, 159 (22 percent) developed atrial fibrillation (AF) at an average of 4.2 years of follow-up.

The prevalence of AF in patients with chronic HF varies from <10 to 50 %, depending in part upon the severity of HF and New York Heart Association class

There is also an association between left ventricular diastolic dysfunction and AF

It should also be kept in mind that each (AF and HF) may predispose or promote the other’s persistent nature

Although the optimal resting heart rate during AF is between 60 and 100 bpm, rates below 100 bpm may not be achievable during AHDF until volume overload and hypoxia have been corrected.

A more realistic target is to achieve a heart rate below 120 bpm during the first hours of treatment

Adverse Hemodynamic Effects of AF

Heart rate changes. In cases where the ventricular response is fast and maintained, a chronic tachycardia can lead to a rate-related cardiomyopathy.

In cases where the ventricular response is exceptionally slow, patients can develop symptomatic bradycardia and possibly syncope.

Activation of neurohumoral vasoconstrictors such as angiotensin II and norepinephrine, as well as other maladaptive and procoagulant biochemical mechanisms.

Adverse Hemodynamic Effects of AF Beat-to-beat variations in atrial pressure (preload). The influence of

preload on left ventricular ejection (Frank-Starling mechanism) is important in AF only when afterload is relatively low .

Beat-to-beat variations in myocardial contractility . Among patients with AF, the preceding RR interval has a significant positive correlation with left ventricular ejection, as a shorter RR interval (more rapid ventricular response) reduces the LVEF . This effect is independent of end-diastolic volume, indicating that it cannot be explained by the Frank-Starling mechanism. In addition, the "pre-preceding" RR interval has a negative correlation with left ventricular ejection, which has been ascribed to postextrasystolic potentiation .

Inefficient ventricular mechanics due to abrupt changes in cycle length .

*p < 0.01

NSR AF VVI VVI VVT 60 AVG

VVI -AVG VVT

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ard

iac

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t (L

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tpu

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Clark DM. JACC 1997; 30:1039-45

Adverse Hemodynamic Effects of AF

Irregular RR Intervals Impair Cardiac Performance

N=16

Atrial systole — Contraction of the left atrium injects a volume of blood under pressure into the left ventricle, leading to increments in ventricular diastolic volume, end-diastolic pressure, and stroke volume .

Loss of atrial systole can therefore diminish the stroke volume. This may be particularly important when left ventricular compliance is reduced and in mitral stenosis.

The importance of atrial systole has been demonstrated in patients with hypertrophic cardiomyopathy, which is typically associated with an increased atrial contribution to ventricular filling (31 versus 16 percent in controls in one report)

Adverse Hemodynamic Effects of AF

Impact on Prognosis in Chronic HF

A three-year follow-up of 6517 patients in the SOLVD trials (patients with asymptomatic left ventricular dysfunction or NYHA class II to III HF) found that AF (present in 6.4 percent) was a significant predictor of all-cause mortality (34 versus 23 percent in those without AF), even after multivariate analysis [7].

The V-HeFT I and II trials included 1427 patients with NYHA class II to III HF, 206 of whom (14 percent) had AF [5]. There was no significant difference in mortality at two years in either trial (34 versus 30 percent and 20 versus 21 percent, respectively) or in hospitalization for HF

EHFS II: A survey on hospitalized AHF patients

AF may worsen symptoms in patients with HF and uncontrolled HF can precipitate or speed the ventricular response of AF

Most patients with AF will have unacceptable symptoms attributable in part to a rapid ventricular rate. These patients require a slowing of the ventricular rate prior to a decision about rhythm or rate control as a long-term strategy to control symptoms.

In the general population of patients with AF, rate control strategy for many might be preferable.

The AF-CHF trial was the first large, randomized trial to test the hypothesis that long-term rhythm control is better than rate control in patients with HF and paroxysmal AF

In this trial, 1376 patients with a left ventricular ejection fraction <35 percent, HF symptoms, and a history of paroxysmal (or persistent) AF were assigned to a strategy of either rhythm control (amiodarone, sotalol, or dofetilide), or rate control (with beta blockers). At a mean follow-up of 37 months, there was no significant difference in the primary outcome of death from cardiovascular causes between the rhythm and rate control groups (27 versus 25 percent, respectively).

This finding is consistent with that in the general population.

For many patients with AF and chronic HF, a rate control is preferred to a rhythm control strategy given the burdens of cost, a more complicated medical regimen, and the potential for adverse side effects of antiarrhythmic therapy. In particular a rate control strategy is an acceptable initial approach to patients who can easily be rate controlled, are very unlikely to maintain sinus rhythm in the long term, and who are not bothered by symptoms such as palpitations that are attributable to AF. Nevertheless, certain circumstances may warrant attempts at rhythm control depending on a patient’s hemodynamic status, severity of symptoms, and ability to adequately control the ventricular response rate.

AHF-AF: Possible Relationships

Atrial fibrillation (AF) is a common arrhythmia, particularly in patients with underlying heart disease. Among patients with both HF and AF, there are several possible relationships:

Acute HF can precipitate AF due to increases in left atrial pressure and wall stress.

AF can cause acute HF, particularly if the ventricular response is rapid.

AF may be chronic and not directly related to the acute HF decompensation.

It is usually difficult to determine whether AF is the cause or result of ADHF.

A reliable history of palpitations that clearly precede the decompensation suggests but does not prove that AF was the cause of the pulmonary edema.

The treatment of AF depends upon whether or not it is associated with significant hemodynamic instability and whether or not it is believed to be the precipitant of HF decompensation.

In some patients with AF and ADHF, effective treatment of pulmonary edema results in slowing of the ventricular rate or spontaneous reversion of the arrhythmia. If AF persists, it is treated in the same fashion as AF in other situations. 

Rate control is often the preferred initial strategy for the following reasons:

Because acute HF can precipitate AF, cardioversion prior to the resolution of acute HF will often be followed by early recurrence of AF.

AF is often a chronic condition that is not contributing to the acute decompensation.

However, if a rate control strategy is selected, the negative inotropic effects of beta-blockers and nondihydropyridine calcium channel blockers can be problematic in patients with systolic dysfunction. For this reason, short-acting IV formulations of such drugs (eg, esmolol or diltiazem) are often used. In addition, digoxin is also potentially useful in this setting, although its use has lessened considerably due to toxicity issues and slow onset of action.

Amiodarone can be considered.

Restoration of sinus rhythm should be considered in the following settings:

If AF is associated with hypotension or evidence of cardiogenic shock

If AF is clearly the cause for pulmonary edema If the response to effective therapy of

pulmonary edema is slow or suboptimal Heparin should be started prior to

cardioversion, whenever possible.

ALARM-HF database

AF in ALARM-HF

no AF Acute AF Acute on chronic

AF

chronic AF

0.0

2.0

4.0

6.0

8.0

10.0

12.0

Mortality (p=0.33)

Mortality

HFSA

Rate and rhythm control of AF

aClass of recommendation. bLevel of evidence.

AF = atrial fibrillation; EHRA = European Heart Rhythm Association.

CHA2DS2VASc score

Rate control of atrial fibrillation

The choice of drugs depends on life style and underlying disease

Acute rate control in AF

aClass of recommendation. bLevel of evidence.

AF = atrial fibrillation; i.v. = intravenous.

Beta-blocker therapy in treatment of atrial fibrillation

Randomized studies have confirmed the superiority of beta-blockers in controlling the ventricular response, especially with exercise.

First, a small population of patients experience recurrent AF in association with stress or anxiety; these patients with adrenergically mediated AF may respond well to beta-blockade

Second, and more common, is the use of beta-blockers for prevention of AF in patients following cardiothoracic surgery (post-op AHF) , in which AF occurs in approx. 30% of patients.

The efficacy of beta-blockers in this circumstance likely relates to the elevated sympathetic tone present postoperatively.

Long-term rate control in AF

aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; bmp = beats per minute; LV = left ventricular; NYHA = New York Heart Association.

AV node ablation in AF patients

aClass of recommendation. bLevel of evidence.

AF = atrial fibrillation; AV = atrioventricular; CRT = cardiac resynchronization therapy; LV = left ventricular;LVEF = left ventricular ejection fraction; NYHA = New York Heart Association.

Choice of an antiarrhythmic drugfor AF control

aClass of recommendation. bLevel of evidence.AF = atrial fibrillation; AV = atrioventricular; LoE = level of evidence; NYHA = New York Heart Association.

Surgical ablation of AF

aClass of recommendation.bLevel of evidence.

AF = atrial fibrillation.

Primary prevention of AFwith “upstream” therapy

aClass of recommendation.bLevel of evidence.

ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker.

Secondary prevention of AFwith “upstream” therapy

aClass of recommendation.bLevel of evidence.

ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker.

Rate control during AF with heart failure

aClass of recommendation.bLevel of evidence.

AF = atrial fibrillation; AP = accessory pathway; LVEF = left ventricular ejection fraction.

Rate control during AF with heart failure

aClass of recommendation.bLevel of evidence.

AF = atrial fibrillation; AV = atrioventricular; CRT = cardiac resynchronization therapy;LVEF = left ventricular ejection fraction; NYHA = New York Heart Association.

Rhythm control of AF in heart failure

aClass of recommendation. bLevel of evidence.

AF = atrial fibrillation; DCC = direct current cardioversion; NYHA = New York Heart Association.

New Trends in Cardiology

April 9-11, 2009

Hyatt Regency Hotel

Thessaloniki

Greece

Atrial Fibrillation in Heart Failure

Background Pathophysiology Influence on disease state and

progression Clinical approach – Management

Heart Failure in the USA

Prevalence: 5 million patients Annual new diagnoses: 550,000 per year Mortality: 54,000 per year Consumption of medical resources:

12 to 15 million office visits / year6.5 million hospital days / year

Predicted steady increase

ACC / AHA Guidelines 2006

0

0,1

0,2

0,3

0,4

0,5

0,6% Patients with Atrial Fibrillation

Atrial fibrillation: prevalence increases with severity of heart failure

Class I – II Class III - IV

Wattigney, W. A. et al. Circulation 2003;108:711-716

Age-specific prevalence (per 10.000 population) of hospitalizations for atrial fib- among adults aged 35 yrs or older by year, 1985 to 1999

Concomitant Heart Failure: 13 % age 35 – 64 yrs 21 % age > 65 yrs

Atrial Fibrillation is Increasing

Development of AF is Associated with Clinical Deterioration in Heart Failure prospective follow-up of 344 patients with CHF and sinus

rhythm for 19 ± 12 months. 28 patients developed AF which became chronic in 18 pts When AF occurred

NYHA class worsened (from 2.4 ± 0.5 to 2.9 ± 0.6, p = 0.0001), peak exercise O2 consumption declined (from 16 ± 5 to 11 ± 5 ml/kg per min, p = 0.002), cardiac index decreased (from 2.2 ± 0.4 to 1.8 ± 0.4, p =

0.0008), mitral and tricuspid regurgitation increased

thromboembolism occurred in 3 of the 18 patients with AF. 9 of 18 patients died after AF occurrence of AF was a predictor of major cardiac events.

Pozolli et al, JACC 1999

Atrial Fibrillation is Associated with Increased Mortality in Chronic HF

RR 1.34 (1.11 - 1.61) adjusted for severity, medication

Atrial Fib- Sinus pn 419 6098

Mortality 34% 23% <0.0001

Heart Failure Death 17% 9% <0.0001

Arrhythmic Death 7% 6% NS

Dries et al, SOLVD, JACC 1998

A) Impact of Treatment of Heart Failure on Atrial Fibrillation - RAAS

Targeting atrial-specific ion channels and developing antiarrhythmic drugs with selected channel-blocking profiles are very attractive approaches.

Success in preventing components of AF pathophysiology, including the prevention of AF-promoting structural remodelling by suppressing renin–angiotensin activation, has been achieved in animal experiments.

Clinical trials indicate the value of inhibiting angiotensin-converting enzyme or blocking angiotensin type-1 receptors in preventing AF recurrence (RAAS).

Antiarrhythmic drugs for atrial fibrillation: Do we need better use, better drugs or a randomized trial of ablation as primary therapy? Stanley Nattel, Montreal Heart Institute Research Center, CMAJ 2004 ; 171 (7).

Prevention of Atrial Fib With Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers: A Meta-Analysis

11 studies with 56,308 patients Overall, ACEIs and ARBs reduced the relative risk of

AF by 28% (95% C] 15% to 40% Benefit is similar for ACE-inhibitors and AII blockers Reduction in AF was greatest in patients with heart

failure (relative risk reduction 44%, p = 0.007).

Healey, et al JACC 2005;45:1832

A) Impact of Treatment of Heart Failure on Atrial Fibrillation - RAAS Aldosterone has a wide range of both genomic and

non-genomic actions and is a potent stimulus for cardiac fibrosis. In addition, aldosterone may produce direct electrophysiological changes.

AF increases serum aldosterone concentrations, whereas restoration of sinus rhythm returns aldosterone concentrations to normal.

Aldosterone production is enhanced by the renin–angiotensin activation occurring in CHF, and it would not be surprising if the resulting mineralocorticoid receptor stimulation contributed to the atrial fibrosis that is an important component of the AF substrate associated with CHF.

Stanley Nattel . Aldosterone antagonism and atrial fibrillation: time for clinical assessment? European Heart Journal 2005 26(20):2079-2080

Milliez P, DeAngelis N, Rucker-Martin C, Leenhardt A, Vicaut E, Robidel E, Beaufils P, Delcayre C, Hatem SN, Spironolactone reduces fibrosis of dilated atria during heart failure in rats with myocardial infarction. Eur Heart J 2005;26:2193–2199. First published on September 1, 2005

Atrial Fibrillation and Heart Failure

Prevention – the best medicineNeurohormonal antagonists

Aggressive therapy of initial AF episodes?

Anticoagulation

Statins?

Targeting heart failure

Thanks for your attention