SECTION 1

Echocardiography in the Evaluation of the Dyspneic Patient

Gerard P. Aurigemma, MD, FAHA, FASE, FACC

CLINICAL CASE PRESENTATION

A 71-year-old woman, who was brought by her family to the emergency room, was admitted to the cardiology service for the evaluation of progressive dyspnea. She is visiting her family from a foreign country. Her major complaint is dyspnea on exertion and episodes of chest pain. The chest pain is nonexertional. The dyspnea began approximately 6 months ago and was thought to be due to deconditioning. However, it has progressed to the point where she can barely walk 50 feet without becoming severely short of breath. The emergency department has diagnosed congestive heart failure, and you are asked to direct further evaluation.

She denies paroxysmal nocturnal dyspnea or orthopnea and is able to lie flat in bed. There is mild peripheral edema. She has occasional spasms of coughing; the cough is not productive. She has lost 8 pounds since the shortness of breath was first noted. The medical history is significant only for hypertension for which she has been prescribed lisinopril and hydrochlorothiazide. She takes these medications faithfully. She is a lifelong nonsmoker and does not drink alcohol.

Examination revealed a frail, elderly woman in no respiratory distress. She becomes dyspneic, however, in moving from her chair to the bed for examination. Vital signs: her blood pressure is 155/70 mm Hg, her heart rate is 92 beats/min and regular, her room air pulse oximetry is 94%, and she is afebrile.

Pertinent exam findings include normal jugular venous pressure, a prominent innominate artery pulsation in the right supraclavicular region, scattered rhonchi, and coarse rales heard throughout the lung fields. The S₁ is normal, as is the S₂. The P₂ is accentuated. There are no murmurs, and there is mild peripheral edema.

Laboratory data is significant for a slightly elevated Troponin I of 0.09 mg/dL and a BNP of 176.

The chest x-ray (Figure 4-1-1) is interpreted as showing prominent interstitial markings, consistent with pulmonary edema. There is also engorgement of the pulmonary vasculature.

FIGURE 4-1-1 Chest x-ray, which was interpreted as showing diffuse interstitial markings, consistent with pulmonary edema and cardiomegaly, with prominent pulmonary artery and venous silhouette.

Her ECG (Figure 4-1-2) shows biatrial enlargement and precordial T-wave inversions, consistent with anterior wall ischemia.

FIGURE 4-1-2 ECG obtained on admission, showing sinus rhythm, right atrial enlargement, and precordial T-wave inversions, consistent with anterior ischemia. Left atrial abnormality is also present.

ECHOCARDIOGRAPHIC EVALUATION

The patient underwent comprehensive echocardiography (Figures 4-1-3 to 4-1-7).

• The findings include normal LV ejection fraction, RV hypertrophy, and pulmonary hypertension, with an RV-RA gradient of 59 mm Hg. The IVC was not well visualized, so the peak pulmonary artery systolic pressure cannot be more precisely assessed, but it is certainly elevated.

• Doppler examination yields clues concerning LA and LV diastolic pressures: the transmitral pattern is A dominant, consistent with abnormal relaxation. The pulmonary venous inflow (Figure 4-1-4) shows clear-cut S dominance. The tissue Doppler early (e’) velocity is 5 cm/s, yielding an E/e’ ratio of 10, which suggests that LA pressure is not elevated.⁴

The clinical and echocardiographic examinations of this patient were consistent with the notion of a noncardiac cause of dyspnea.

• This is based on the findings of LA pressure which is not elevated, based on the transmitral inflow pattern of low E/A ratio; the pulmonary venous inflow pattern, which is S dominant; and the E/e’ which is not elevated.⁴

FIGURE 4-1-3 Transmitral inflow profile, showing low E/A ratio and low absolute E velocity.

FIGURE 4-1-4 Pulmonary venous inflow pattern obtained with the sample volume in the right upper pulmonary vein; this was interpreted as showing low left atrial pressure.

FIGURE 4-1-5 Tissue Doppler spectral profile obtained with the sample volume in the lateral annulus. While this velocity is low at 5 cm/s, the E/e’ ratio is 50 cm/s ÷ 5 cm/s = 10, which is not consistent with elevated LA pressure.

FIGURE 4-1-6 TR profile showing peak RV to RA gradient of 59 mm Hg, consistent with elevated RV systolic pressure.

FIGURE 4-1-7 Parasternal long axis demonstrating normal LV size and EF. The RV outflow tract appears dilated and hypertrophied

DIAGNOSIS

Based on the cardiologist’s clinical evaluation and the results of the echocardiogram, the dyspnea was felt most likely due to the pulmonary disease, and pulmonary hypertension was felt not to be passive, ie, due to elevated LA pressure⁵. Electrocardiographic findings were deemed to be consistent with idiopathic pulmonary hypertension. These include right atrial enlargement and precordial T-wave inversions, thought to represent an RV strain pattern.

HOSPITAL COURSE

The patient was evaluated by the pulmonary medicine service. She underwent CT scanning of the chest (Figure 4-1-8). This study demonstrated diffuse interstitial fibrosis, and eventually the diagnosis of idiopathic pulmonary fibrosis was made. She was subsequently discharged with follow-up with the pulmonary medicine team.

FIGURE 4-1-8 CT scan of chest obtained on third hospital day; this was interpreted as showing evidence of diffuse interstitial fibrosis, consistent with the diagnosis of idiopathic pulmonary fibrosis.

DYSPNEA

• Dyspnea was the presenting symptom for this patient. Whether it occurs either at rest or with exertion, dyspnea is a cardinal symptom of heart disease.

• It can be difficult, at the bedside, to distinguish among the various etiologies of dyspnea, which, in addition to heart and lung disease, include deconditioning, anemia, or anxiety/hyperventilation.

• Dyspnea accompanying obvious signs of left heart disease strongly suggests a cardiac etiology, but these signs were not present in this patient.

• As was shown in this case, echocardiography is an essential component of the initial evaluation of the patient with dyspnea. It may help to elucidate the origin of dyspnea by documenting or ruling out the common cardiac causes of pulmonary congestion: left-sided valvular disease, depressed systolic function, diastolic dysfunction, and cardiomyopathy.

• For this reason, echocardiography is an important initial diagnostic test when the history, physical examination, and routine laboratory tests suggest or cannot eliminate cardiac disease.

ADDITIONAL DIAGNOSTIC TESTS IN THE EVALUATION OF DYSPNEA

Depending on the initial history and physician examination findings, as well as baseline laboratory studies (cbc, chemistries), further diagnostic tests may be warranted:

• Chest x-ray (to assess for pneumonia, underlying lung disease)

• Pulmonary function studies

• 6-minute walk test

• Cardio-pulmonary exercise test (to differentiate pulmonary from cardiac etiologies)

• Cardiac stress test (to assess for myocardial ischemia)

• Chest CT

• CT pulmonary angiogram or ventilation-perfusion scan to rule out pulmonary emboli

ECHOCARDIOGRAPHY IN THE EVALUATION OF THE DYSPNEIC PATIENT

Echocardiography is clearly indicated in the evaluation of the dyspneic patient when there is a clinical suspicion for a cardiac contribution to the patient’s symptoms.^1,2,3,6

• The 2011 Appropriate Use Guidelines for echocardiography lists: “Symptoms or conditions potentially related to suspected cardiac etiology including but not limited to chest pain, shortness of breath, palpitations, TIA, stroke, or peripheral embolic event” and “Prior testing that is concerning for heart disease or structural abnormality including but not limited to chest X-ray, baseline scout images for stress echocardiogram, ECG, or cardiac biomarkers” as appropriate indications for echocardiography, with a score of 9 (the highest possible) for each.¹

• One of the principal findings in this patient was that systolic function was normal. In fact, of all the indications for echocardiography, the evaluation of ventricular systolic function is the most common. Krumholz, et al,⁷ has shown that evaluation of LV systolic function was the primary indication for TTE in 26% of inpatients studied, a frequency at least twice that of the next most common indication.

• A comprehensive echocardiographic examination includes assessment of LV size and function, as well as information concerning diastolic function^4,6 filling pressures, and an estimate of pulmonary artery systolic pressure.⁸

• In this instance, as we have seen, resting diastolic function was consistent with grade I diastolic dysfunction. Such diastolic dysfunction is usually not associated with elevated filling pressures at rest.^4,9 Furthermore, while many if not most patients with pulmonary hypertension in clinical practice have elevated left-sided filling pressures as the etiology,¹⁰ this was most likely not the case in this patient.

• Other cardiac etiologies that might account for dyspnea include valvular heart disease, especially mitral valve stenosis and/or regurgitation, aortic valve disease, tricuspid regurgitation, and pericardial disease. The echocardiogram in this patient quickly ruled out these etiologies.

REFERENCES

  1. Douglas PS, Garcia MJ, Haines DE, et al. ACCF/ASE/AHA/ASNC/HFSA/HRS/SCAI/SCCM/SCCT/SCMR 2011 appropriate use criteria for echocardiography: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Society of Echocardiography, American Heart Association, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Critical Care Medicine, Society of Cardiovascular Computed Tomography, and Society for Cardiovascular Magnetic Resonance. J Am Coll Cardiol. 2011;57(9):1126-1166. doi:10.1016/j.jacc.2010.11.002.

  2. Patel MR, White RD, Abbara S, et al. 2013 ACCF/ACR/ASE/ASNC/SCCT/SCMR appropriate utilization of cardiovascular imaging in heart failure: a joint report of the American College of Radiology Appropriateness Criteria Committee and the American College of Cardiology Foundation Appropriate Use Criteria Task Force. J Am Coll Cardiol. 2013;61:2207–2231. doi:10.1016/j.jacc.2013.02.005. This document is available on the World Wide Web sites of the American College of Cardiology (http://www.cardiosource.org) and the American College of Radiology (http://www.acr.org).

  3. Yancy CW, Jessup M, Bozkurt B, et al. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013;62:e147–239. This document is available on the World Wide Web sites of the American College of Cardiology (www.cardiosource.org) and the American Heart Association (my.americanheart.org).

  4. Nagueh SF, Appleton CP, Gillebert TC, et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography. Eur J Echocardiogr. 2009;10(2):165-193.

  5. Bouchard JL, Aurigemma GP, Hill JC, Ennis CA, Tighe DA. Usefulness of the pulmonary arterial systolic pressure to predict pulmonary arterial wedge pressure in patients with normal left ventricular systolic function. Am J Cardiol. 2008;101(11):1673-1676.

  6. Douglas PS, Hendel RC, Cummings JE, et al. ACCF/ACR/AHA/ASE/ASNC/HRS/NASCI/RSNA/SAIP/SCAI/SCCT/SCMR 2008 Health Policy Statement on Structured Reporting in Cardiovascular Imaging. Endorsed by the Society of Nuclear Medicine [added]. Circulation. 2009;119(1): 187-200.

  7. Krumholz HM, Douglas PS, Goldman L, Waksmonski C, Clinical utility of transthoracic two-dimensional and Doppler echocardiography. J Am Coll Cardiol. 1994;24(1):125-131.

  8. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber quantification: a report from the American Society of Echocardiography’s Guidelines and Standards Committee and the Chamber Quantification Writing Group, developed in conjunction with the European Association of Echocardiography, a branch of the European Society of Cardiology. J Am Soc Echocardiogr. 2005;18(12):1440-1463.

  9. Aurigemma GP, Gaasch WH. Clinical practice. Diastolic heart failure. N Engl J Med. 2004;351(11):1097-1105.

10. Lam CS, Lyass A, Kraigher-Krainer E., et al. Cardiac dysfunction and noncardiac dysfunction as precursors of heart failure with reduced and preserved ejection fraction in the community. Circulation. 2011;124(1):24-30.

SECTION 2

Alcoholic Cardiomyopathy

Rebecca Baumann, MD, and Gerard P. Aurigemma, MD, FAHA, FASE, FACC

CLINICAL CASE PRESENTATION

A 48-year-old man with paroxysmal atrial fibrillation (not on anticoagulation), hypertension, hyperlipidemia, Type 2 diabetes mellitus, COPD, longstanding heavy tobacco and alcohol use, and dialysis-dependent end-stage renal disease presented to the emergency department with chest pressure, palpitations, shortness of breath and a nonproductive cough of 1 day’s duration. The symptoms began after carrying a bicycle upstairs. He had had similar but much less intense dyspnea and coughing in the past. He denied any change in the chest discomfort with inspiration or position, lightheadedness, swelling, fevers, chills, sweating, or nausea. That day he had opted to forgo his dialysis as it was his daughter’s birthday. His last dialysis session had been 3 days prior to presentation. On further review of his social history, the patient volunteered that for the past 6 to 9 months he had been drinking heavily, consuming up to 1 quart of vodka per day.

An initial ECG showed atrial fibrillation with an average ventricular rate of 143 bpm and a left bundle branch block (Figure 4-2-1). After the administration of intravenous diltiazem, his heart rate and blood pressure stabilized. His breathing was not labored or rapid, but he did require 2 L/min of oxygen. His exam was remarkable for bibasilar crackles and an S₃ gallop. A chest x-ray demonstrated mild cardiomegaly, pulmonary vascular congestion, and pulmonary edema. His troponin I peaked at 0.17 ng/mL and BNP was 4537 pg/mL. Electrolytes were within normal limits. CBC was significant for a mild leukocytosis. A repeat ECG confirmed that normal sinus rhythm had been restored (Figure 4-2-2). Over the next 24 hours his respiratory status worsened, and he was eventually transferred to the ICU for BiPAP and emergent dialysis.

FIGURE 4-2-1 Admission ECG demonstrating rapid atrial fibrillation and left bundle branch block

FIGURE 4-2-2 Repeat ECG demonstrates restoration of normal sinus rhythm; however, left bundle branch block persists.

A transthoracic echocardiogram at the time of dialysis revealed LV dilatation with LVEF of 30%, global hypokinesis, increased wall thickness, restrictive diastolic physiology, a moderately dilated left atrium and mild pulmonary hypertension. Doppler analysis was consistent with elevated mean left atrial pressure (Figures 4-2-3 to 4-2-7).

FIGURE 4-2-3 Parasternal long axis view demonstrating a dilated, hypokinetic LV.

FIGURE 4-2-4 Apical 4 chamber view demonstrating 4 chamber enlargement. There is significant LV and RV hypokinesis.

FIGURE 4-2-5 Apical 4 chamber view with color Doppler demonstrating significant MR.

FIGURE 4-2-6 Pulsed Doppler at level of the mitral valve after normal sinus rhythm has been restored; this filling pattern is “restrictive” with high E velocity, rapid deceleration time, and absent A wave. The lack of an A wave despite restoration of normal sinus rhythm is consistent with either an atrial myopathy or atrial stunning.

FIGURE 4-2-7 Tissue Doppler obtained at the lateral mitral annulus. The E/e’ ratio is consistent with elevated mean LA pressure.

The patient had undergone cardiac catheterization 4 months prior to this admission (performed as a follow-up of an equivocal nuclear stress test results, which had been ordered as part of an evaluation for kidney transplant). The coronary arteriogram demonstrated minor luminal irregularities.

On review of his previous ECGs it was noted that the LBBB had been present 2 months prior but that his QRS complexes were normal 1 year ago (Figure 4-2-8).

FIGURE 4-2-8 ECG performed approximately 1 year prior to admission demonstrating normal sinus rhythm and narrow QRS complex.

Given his echocardiographic findings and social history in addition to his lack of significant coronary artery disease, he was presumptively diagnosed with an alcoholic cardiomyopathy. His decompensation was attributed to a combination of volume overload due to missed dialysis, exercise, and tachycardia due to paroxysmal atrial fibrillation with poor rate control, as well as the malefic effects on LV filling of the left bundle branch block.

With medical management of his heart failure, initiation of amiodarone to maintain sinus rhythm, and more aggressive ultrafiltration, the patient’s clinical status soon improved dramatically, with resolution of his dyspnea and chest pain syndrome. The patient has abstained from alcohol use. A follow-up echocardiogram, performed 6 months later, demonstrated normal LV function and reduction in the severity of mitral regurgitation (Figures 4-2-9 and 4-2-10).

FIGURE 4-2-9 Parasternal long axis follow-up echo demonstrating improvement in LV dimensions and EF. The atria remain dilated.

FIGURE 4-2-10 Apical 4 chamber view with color Doppler demonstrating an improvement in the MR.

EPIDEMIOLOGY

Alcoholic cardiomyopathy (ACM) is the most common cause of nonischemic dilated cardiomyopathy in the western world, comprising 21% to 36% of all cases.¹

• Both systolic and diastolic LV dysfunction as well as systolic RV dysfunction can occur.

• It is believed that diastolic impairment may be an early harbinger of ACM as this is seen in 30% to 40% of alcoholics with normal systolic function and in two-thirds of those with systolic dysfunction.^2,3

• An EF ≤50% has been reported in approximately 13% of heavy drinkers (lifetime alcohol consumption of 9 kg/kg body weight),³ while another study claims the incidence of cardiomyopathy in chronic alcoholics is as high as 50%.⁴

• Men comprise the majority of ACM cases at roughly 86%⁵ despite the increased sensitivity to toxic effects of alcohol in women.⁶

• In ACM patients, the 4-year mortality without alcohol abstinence is estimated at 50%.⁵

ETIOLOGY AND PATHOPHYSIOLOGY

Cardiotoxicity varies with both the amount of alcohol ingested and the duration of drinking above this threshold.⁷ There is wide variation among studies as to what constitutes a “drink” and “mild,” “moderate,” and “heavy” drinking.

• In the US the common definition of a standard alcoholic drink is 14 g of alcohol (12 oz beer, 5 oz wine, 1.5 oz or “shot” of 80-proof distilled spirits or liquor).² It is thought that in order to develop ACM, men must consume on average 80 g of ethanol per day for a period of 5 to 15 years.^1,7 Women require less to achieve the same cardiotoxic effects.⁶ The increased sensitivity to alcohol seen in women is possibly due to slower gastric metabolism and accelerated hepatic metabolism, leading to a net increase in the level of toxic metabolites.

There are many putative mechanisms leading from excessive alcohol consumption to ACM, but it is also fair to say that the mechanism is not fully understood.

• Nutritional deficiencies are no longer thought to play a major role.

• Proposed mechanisms of direct injury include oxidative stress with buildup of reactive oxygen species (ROS). These ROS cause myocyte hypertrophy and apoptosis, which lead to remodeling.⁸

• Changes in the myofibrillary architecture and decreased myocardial contractility occur as well.⁴

    On electron microscopic studies of animals with induced ACM histologic findings include dilated sarcoplasmic reticula, swollen mitochondria with fragmented cristae and glycogen-filled vacuoles, myofibrillar degeneration and fibrosis, and collagen accumulation in the extracellular matrix.

• It is also believed that increases in norepinephrine levels and derangements in the renin-angiotensin-aldosterone system contribute.

• Finally, structural changes may reflect other cardiovascular effects of alcohol including hypertension, hyperlipidemia, and arrhythmias.

• Several genetic mechanisms which may predispose to ACM have also been proposed, prompted by the observation that only a minority of chronic alcohol abusers will go on to develop this condition.

    It is well established that a certain genotype of the angiotensin converting enzyme (ACE-DD) is associated with heart failure in patients with both ischemic and dilated cardiomyopathy. One study showed the prevalence of this allele in alcohol abusers with symptomatic dilated cardiomyopathy to be 57% versus only 7% in abusers with normal systolic function. The odds ratio for development of ACM in alcoholics with the DD allele was 16.4 compared to those with the I allele.^9,10

    Other genetic polymorphisms implicated in development of ACM are involved in the metabolism of ethanol. Defective variants of acetaldehyde dehydrogenase and alcohol dehydrogenase (ADH) lead to accumulation of the highly cardiotoxic metabolite, acetaldehyde,⁸ which concentrates in the heart and is far more reactive than ethanol. Increased levels of acetaldehyde due to overexpression of ADH have been demonstrated in alcoholics.⁴ The acetaldehyde was also shown to hinder the coupling of myocyte excitation and contraction by inhibiting release of intracellular calcium from the sarcoplasmic reticulum.

• Illegally produced alcohol often contains additives such as lead and cobalt, which themselves are cardiotoxic.

• Heavy alcohol consumption is also frequently accompanied by electrolyte imbalances (hypokalemia, hypomagnesemia, hypophosphatemia), which further contribute to myocyte dysfunction, arrhythmias and structural alterations.

DIAGNOSIS

Clinical Features

Obtaining a careful clinical history is imperative. Of singular importance is the presence of long-standing heavy alcohol consumption. Frequently, patients will downplay this, and repeated, pointed, yet nonjudgmental questioning may be necessary to elicit this history.¹

Patients with ACM will exhibit typical signs and symptoms of both systolic and/or diastolic heart failure. As mentioned, a significant number will have impaired LV function long before symptoms become apparent.⁵

• Dyspnea with exertion (and eventually at rest), dry cough, orthopnea, PND, chest heaviness, and fatigue all signal the transition to decompensation.

• Palpitations may occur and are usually due to supraventricular tachyarhythmias.

• Physical exam may reveal an S₃ or S₄ gallop, a systolic apical murmur of mitral regurgitation (due to papillary muscle dysfunction), crackles, and decreased pulse pressure from elevated diastolic pressure secondary to peripheral vasoconstriction.

• In advanced stages, signs and symptoms of RV dysfunction may also become evident including elevated JVP, peripheral edema, and ascites.

ECHOCARDIOGRAPHY

One definition of alcoholic cardiomyopathy is LV dilatation, increased LV mass, normal or decreased wall thickness in the setting of 5 to 10 years of heavy drinking, and absence of ischemia or other causes.^5,7

• As in all forms of non-ischemic cardiomyopathy, systolic dysfunction is a hallmark. Diastolic impairment, however, often precedes this and even more frequently accompanies systolic dysfunction.³

• Early in the course of ACM, an increase in the relative wall thickness is found, with 4 chamber dilatation with associated valvular regurgitation eventually supervening.

• An elevated LV mass index, atrial contraction (A wave), and deceleration time with a reduced E wave and E/A ratio.³

• The fate of the RV in ACM has not been widely researched; however, one study showed a U-shaped dose-response curve with both LV and RV size where RV dilatation occurred only with very heavy drinking (>180 g/d) and paralleled the increase in LV size.¹¹

OTHER LABORATORY STUDIES

All patients with a suspected cardiomyopathy should undergo a basic evaluation including a CXR, ECG and a basic metabolic panel. Nonspecific findings in ACM may include elevated BNP, ESR, and CRP, as well as low potassium, magnesium, sodium, and phosphorous.

• Laboratory studies suggestive of alcohol abuse may help to support the diagnosis:

    Typical hematologic and chemical abnormalities found in alcohol abuse include abnormal levels of B12, folic acid, thiamine and zinc, as well as elevated MCV, MCH, transaminases, γ-glutamyltranspeptidase, PT/INR, and a low platelet count.

• Endomyocardial biopsy:

    Usually not necessary as the echocardiographic findings along with the clinical history generally suffice to make the diagnosis of ACM.

    Biopsy may be useful to distinguish certain types of myocarditis-induced or infiltrative cardiomyopathies. Once fibrosis has set in, the utility of this study declines significantly.

DIFFERENTIAL DIAGNOSIS

The differential diagnosis of a dilated cardiomyopathy includes:

• Tachycardia-mediated cardiomyopathy

• Stress-induced cardiomyopathy

• Idiopathic dilated cardiomyopathy

• Chronic volume overload due to inadequate dialysis

• Chemotherapy-related cardiomyopathy

MANAGEMENT

Conventional medical therapy for heart failure is warranted. This includes β-blockers, ACE-inhibitors/ARBs, diuretics, digoxin, fluid and sodium restriction. Nutritional deficiencies (thiamine, B12, and folate deficiencies) and electrolyte abnormalities, often seen in chronic alcoholism, should also be corrected.

Essential for the treatment of ACM is abstinence from or significant reduction in alcohol consumption. It has been well demonstrated that this can lead to partial or even full recovery of LV function.⁷

• After 1 year of abstinence, LVEF has been shown to improve by 13% with similar results in patients who reduced their consumption to 20 to 60 g/d.¹² Seventy-five percent of those who continued to drink >80 g/d (even if they had significantly cut down from their previous consumption) passed away within 4 years of follow-up.

PATIENT EDUCATION AND FOLLOW-UP

Patients must be educated on the adverse effects of alcohol on the heart. Referral to an alcohol treatment program is appropriate. The importance of compliance with an ongoing medical regimen for chronic CHF must be emphasized. Regular follow-up with a cardiologist is warranted. As noted above, the LVEF may improve with cessation of alcohol use and/or the institution of medical therapy, which may allow for a tailoring of medical therapy. A repeat echocardiogram after 3 to 6 months of therapy is thus warranted to reassess LVEF and guide the need for other therapies such as CRT and/or ICD placement (see other sections in this chapter).

REFERENCES

  1. Skotzko CE. Alcohol use and congestive heart failure: incidence, importance, and approaches to improved history taking, Heart Fail Rev. 2009;14:51-55.

  2. Kloner RA. To drink or not to drink? That is the question. Circulation. 2007;116(11):1306-1317.

  3. Fernandez-Sola J. Diastolic function impairment in alcoholics. Alcohol Clin Exp Res. 2000;12(24):1830-1835.

  4. Duan J. Overexpression of alcohol dehydrogenase exacerbates ethanol-induced contractile defect in cardiac myocytes. Am J Physiol Heart Circ Physiol. 2002;282(4):H1216-H1222.

  5. Laonigro I. Alcohol abuse and heart failure, Eur J Heart Fail. 2009;11(5):453-462.

  6. Urbano-Màrquez A. The greater risk of alcoholic cardiomyopathy and myopathy in women compared with men. JAMA. 1995;274:149-154.

  7. Djousse L. Alcohol consumption and heart failure: a systematic review. Curr Atheroscler Rep. 2008;10(2):117-120.

  8. Lucas DL. Alcohol and the cardiovascular system: research challenges and opportunities. J Am Coll Cardiol. 2005;45(12):1916-1924.

  9. Fernandez-Sola J. Angiotensin-converting enzyme gene polymorphism is associated with vulnerability to alcoholic cardiomyopathy. Ann Intern Med. 2002;137:321-326.

10. Pilati M. The role of angiotensin-converting enzyme polymorphism in congestive heart failure. CHF. 2004;10:87-95.

11. Kajander OA. Dose dependent but non-linear effects of alcohol on the left and right ventricle. Heart. 2001;86:417-423.

12. Nicolàs JM. The effect of controlled drinking in alcoholic cardiomyopathy. Ann Intern Med. 2002;136:192-200.

SECTION 3

Tachycardia-Mediated Cardiomyopathy

Gaurav R Parikh, MD, MRCP (UK) and Gerard P. Aurigemma, MD, FAHA, FASE, FACC

CLINICAL CASE PRESENTATION

A 65-year-old woman with a history of mitral valve prolapse, treated breast cancer, hypothyroidism, and hyperlipidemia presented to her physician with symptoms of dyspnea. She was initially treated with antibiotics for a presumptive diagnosis of pneumonia. However, she continued to have symptoms of significant dyspnea and was referred for further workup. Upon presentation to the echo lab, she was noted to be tachycardic, and an ECG confirmed her to be in atrial fibrillation with rapid ventricular rate of 150 bpm (Figure 4-3-1). A chest radiograph (Figure 4-3-2) showed cardiomegaly, bilateral pleural effusions, and vascular congestion. An echocardiogram revealed a dilated, spherical left ventricle with severely reduced LV ejection fraction and severe mitral regurgitation (Figures 4-3-3 and 4-3-4). Right and left heart cardiac catheterization was performed, which demonstrated no obstructive coronary disease. Tracings from that procedure are seen in Figure 4-3-5 A and B; pulmonary hypertension was noted, and there was a sizeable ‘v’ wave noted in the pulmonary capillary wedge tracing.

FIGURE 4-3-1 ECG showing atrial fibrillation with rapid ventricular response.

FIGURE 4-3-2 CXR showing bilateral pleural effusions and pulmonary vascular congestion.

FIGURE 4-3-3 M-mode taken from the initial echocardiogram; M-mode cursor is directed through the LV showing the dilated LV cavity. There is marked LV dilation; diastolic dimension is 6.7 cm.

FIGURE 4-3-4 Apical 4 chamber view (top panel) and 2 chamber view with color Doppler (bottom panel). The echo shows LV dilation, tachycardia, and marked diminution of global systolic function. Note also, biatrial enlargement, severe mitral annular calcification, and myxomatous degeneration of the mitral valve. Apical 2 chamber view with color flow Doppler mapping demonstrates a broad area of flow turbulence in the left atrium in systole, indicative of severe mitral regurgitation. There is a large area of flow convergence in the left ventricle. Note also rapid heart rate and severe systolic dysfunction.

FIGURE 4-3-5 A Pulmonary artery pressure tracing documenting significant pulmonary hypertension, with peak systolic pressure in the 50 to 56 mm Hg range, and pulmonary artery diastolic pressure averaging 28 to 30 mm Hg. B Composite of pulmonary capillary wedge and left ventricular pressure tracings. (The PCW tracing is phase delayed, so the peak ‘v’ wave does not coincide with diastole.) Note the high mean pulmonary PCW pressures with elevated v waves to as much as 30 mm Hg.

The patient underwent successful cardioversion back to normal sinus rhythm, and a heart failure medical regimen was initiated. Echocardiography performed approximately 4 weeks later demonstrated improved systolic function, but also persistent chamber dilation (Figure 4-3-6). In addition, there was persistent severe mitral regurgitation. A subsequent echocardiogram performed 4 months later demonstrated normalization of LV size but there was persistent severe mitral regurgitation (Figure 4-3-7). Accordingly, she subsequently underwent mitral valve repair with annuloplasty and a modified biatrial Cox procedure and left atrial appendage resection. Upon follow-up, she was remarkably better without any symptoms or signs of heart failure, and her echocardiogram showed eventual normalization of LV cavity dimensions and normal LV ejection fraction.

FIGURE 4-3-6 Parasternal long axis view 4 weeks postcardioversion showing persistently dilated LV cavity (LVIDD 6.9 cm).

FIGURE 4-3-7 An echocardiogram performed 4 months post cardioversion demonstrated marked improvement in LV dilatation (LVIDD 5.5 cm). The accompanying 2 videos demonstrate improved LVEF but persistent significant MR.

CLINICAL FEATURES

• The clinical presentation of tachycardia-mediated cardiomyopathy can be extremely variable.

• Patients may present with palpitations related to the uncontrolled heart rate and irregularity of the underlying arrhythmia.

• Alternatively, they may present with signs and symptoms of congestive heart failure: fatigue, shortness of breath, paroxysmal nocturnal dyspnea, orthopnea, and pedal edema.

• Accordingly, the physical examination, apart from the rapid heart rate, can be variable. If heart failure is the presentation, there will be elevated JVP, S₃ gallop, mitral regurgitation murmur, and pedal edema. Lung examination may show the presence of pleural effusion and basilar rales.

BACKGROUND AND EPIDEMIOLOGY

Cardiomyopathy is a group of disorders caused by abnormal myocardial structure and function in absence of ischemic heart disease, hypertension, or valvular disease.

• Phenotypic classification is based on the anatomy and physiology. Categories include dilated, hypertrophic, restrictive, arrhythmogenic right ventricular and unclassified.¹

• It has been known for some time that chronic rapid heart rates can cause a dilated type of cardiomyopathy that is highly reversible upon control of the tachycardia. While the exact incidence of tachycardia-mediated cardiomyopathy is not known, it is being increasingly recognized as an important cause of dilated cardiomyopathy.^1,2

PATHOPHYSIOLOGY AND ETIOLOGY

• Dilated cardiomyopathy has been described in chronic and incessant tachycardia from atrial fibrillation, atrial flutter, atrial tachycardia, accessory pathway mediated tachycardia, and AV nodal reentry tachycardia as well as with incessant ventricular tachycardia.^2–4

• Animal models that were originally developed to investigate heart failure have helped immensely to understand tachycardia-mediated cardiomyopathy.

    In experimental animal models, rapid pacing produces hemodynamic changes such as a fall in blood pressure and a drop in cardiac output as early as 24 hours with continued deterioration in ventricular function for up to 3 to 5 weeks, leading to marked biventricular dilatation and end-stage heart failure.

    The LV assumes a more spherical shape with thinning of the LV walls. There is apical and lateral displacement of the papillary muscles leading to tenting and tethering of mitral leaflets causing secondary mitral regurgitation.²

• Several mechanisms have been described to account for contractile dysfunction and structural changes:

    Myocardial energy depletion and impaired utilization, abnormal calcium handling, myocardial ischemia, and myocyte and extracellular matrix remodeling have all been described.

    At the cellular level, there is disruption of extracellular matrix architecture and myocyte basement membrane-sarcolemmal interface. There are morphologic changes in myocyte itself with myocyte loss and increase in volume of the remaining myocytes.²

• There is intense neurohumoral activation with marked elevation of atrial natriuretic peptide, epinephrine, norepinephrine, renin activity, and aldosterone levels.²

ECHOCARDIOGRAPHY

Patients with signs and symptoms of heart failure should be evaluated with an echocardiogram. There are several features of a dilated cardiomyopathy that can be assessed.⁵

• 2-D and M-mode echocardiography will show marked biventricular dilatation. The left ventricle assumes spherical geometry with sphericity index <1.5:1.

• Thinning of the ventricular walls is noted.

• There can be enlargement of the right ventricle and both the atria.

• There is markedly increased end-systolic and end-diastolic LV volumes and markedly reduced systolic function.

• Geometric changes in the shape of the LV as well as geometric changes resulting in apical and lateral displacement of the papillary muscles are seen. This may lead to apical tenting of the mitral apparatus causing functional mitral regurgitation.

• The LV apex should be examined carefully in cases with severely reduced systolic function to look for apical thrombus.

• M-mode echocardiography at the level of mitral leaflet tips will show increased E-point to septal separation (EPSS) distance indicating dilated LV cavity and reduced LV systolic function (Figure 4-3-8).

• Reduced mitral leaflet opening and premature tapering and closure of aortic cups are noted on M-mode consistent with reduced stroke volume.

• A “B-bump” (Figure 4-3-9) may be noted at the level of mitral tips indicating elevated LV filling pressures.

• Doppler echocardiography will help assess the LV filling pressure by looking at the mitral inflow pattern.

    A steep mitral E wave deceleration slope of <130 ms and a ratio of E/e’ >20 is associated with elevated left atrial pressures and elevated left ventricular filling pressures.

    An E/e’ <10 is associated with normal left atrial pressure.

• The presence and severity of mitral and tricuspid regurgitation add prognostic value, with a general rule of thumb being worse prognosis with worsening mitral and tricuspid regurgitation.⁶

FIGURE 4-3-8 M-mode at the level of mitral leaflet tips in a patient with dilated cardiomyopathy with severely reduced systolic function showing increased EPSS = 3cm.

FIGURE 4-3-9 M-mode at the level of mitral leaflet tips in a patient with dilated cardiomyopathy with severely reduced systolic function. Broad arrows indicate an interruption in the smooth closure motion of the anterior leaflet of the mitral valve in late diastole, indicating a “B-bump” or “A-C” shoulder. This finding denotes an elevation in post-atrial systole ventricular diastolic pressure.

OTHER DIAGNOSTIC TESTING AND PROCEDURES

A clinical evaluation should always begin with a careful history concerning the onset and type of symptoms.

• An ECG will give crucial information regarding the heart rate and rhythm.

• Holter monitoring or telemetry are used to diagnose any and all arrhythmias and to better understand the heart rate variability.

• Chest radiograph will show evidence of cardiomegaly. It may show right-sided pleural effusion and/or pulmonary vascular congestion.

• Radionuclide imaging may be of value in ruling out myocardial ischemia as well as assessing ventricular volumes and ejection fraction in cases where echocardiogram is suboptimal.

• Cardiac MRI can not only accurately assesses ventricular function, but it can also be immensely helpful in distinguishing inflammatory from infiltrative cardiomyopathies, as well as identify patients who have evidence of replacement fibrosis and are at high risk of sudden cardiac death due to electrical instability.⁷

• Cardiac catheterization, in this era, is generally reserved for assessing the presence and extent of coronary artery disease and to document filling pressures, as was done in this case.

DIFFERENTIAL DIAGNOSIS

The main differential diagnosis of tachycardia-mediated cardiomyopathy is a dilated cardiomyopathy from other causes: idiopathic, post-viral, HIV-related, familial, drugs, alcohol, and chemotherapy. Echocardiographically, these may exhibit a very similar phenotype, and the differentiation is provided by the history and other clinical features.

DIAGNOSIS

The diagnosis is usually made by careful history, physical examination, an ECG showing tachycardia with the echocardiographic features outlined above. Cardiac catheterization is useful to rule out underlying coronary disease.⁸

MANAGEMENT

The main emphasis of management of tachycardia-mediated cardiomyopathy is to terminate the arrhythmia and either establish sinus rhythm or control the ventricular response, either with medications or an AV nodal ablation/pacemaker. A secondary emphasis is on treating the heart failure with a medical regimen of diuretics, angiotensin converting enzyme inhibitor or angiotensin receptor antagonist, β-blockers, and an aldosterone antagonist.⁸

FOLLOW-UP

The patient should be followed up closely with a cardiologist/primary care physician. It should be reemphasized that tachycardia-mediated cardiomyopathy is highly reversible once the underlying arrhythmia is treated. The majority of cases will normalize their left ventricular size and systolic function.

REFERENCES

1. Maron BJ, Towbin JA, Thiene G, et al. Contemporary definitions and classification of the cardiomyopathies: an American Heart Association Scientific Statement from the Council on Clinical Cardiology, Heart Failure and Transplantation Committee; Quality of Care and Outcomes Research and Functional Genomics and Translational Biology Interdisciplinary Working Groups; and Council on Epidemiology and Prevention. Circulation. 2006;113:1807.

2. Shinbane JS, Wood MA, Jensen DN, et al. Tachycardia-induced cardiomyopathy: a review of animal models and clinical studies. J Am Coll Cardiol. 1997;29:709.

3. Kasper EK, Agema WR, Hutchins GM, et al. The causes of dilated cardiomyopathy: a clinicopathologic review of 673 consecutive patients. J Am Coll Cardiol. 1994;23:586.

4. Redfield MM, Kay GN, Jenkins LS, et al. Tachycardia-related cardiomyopathy: a common cause of ventricular dysfunction in patients with atrial fibrillation referred for an atrioventricular ablation. Mayo Clinic Proc. 2000;75:790.

5. Armstrong WF, Ryan T. Feigenbaum’s Echocardiography 7^th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2009.

6. Koelling TM, Aaronson KD, Cody RJ, Bach DS, Armstrong WF. Prognostic significance of mitral regurgitation and tricuspid regurgitation in patients with left ventricular systolic dysfunction. Am Heart J. 2002;144:524-529.

7. Nazarian S, Bluemke DA, Lardo AC, et al. Magnetic resonance assessment of the substrate for inducible ventricular tachycardia in nonischemic cardiomyopathy. Circulation. 2005;112:2821.

8. Jessup M, Abraham WT, Casey DE, et al. 2009 focused update: ACCF/AHA Guidelines for the Diagnosis and Management of Heart Failure in Adults: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines: developed in collaboration with the International Society for Heart and Lung Transplantation. Circulation. 2009;119:1977.

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