Evidence-Based Approach to Feline Diastolic Heart Failure

Medical guidelines should insists on proof that time-honored medical practices and procedures that cost money and may harm or kill patients are actually effective. This Forum is about how to force organized veterinary medicine to issue Evidence Based Guidelines.

Evidence-Based Approach to Feline Diastolic Heart Failure

Postby malernee » Thu Mar 18, 2004 1:43 pm

Evidence-Based Approach to Feline Diastolic Heart Failure
ACVIM 2003
Philip R. Fox, DVM, DACVIM (Cardiology)
New York, NY


Diastolic dysfunction is the principal pathophysiologic consequence of a group of phenotypically heterogeneous myocardial diseases. A variety of complex intrinsic and extrinsic factors affect left ventricular diastolic performance including loading conditions; myocardial mass (hypertrophy); right ventricular pressure; pericardial restraint and pleural pressure; metabolic derangements, myocardial injury (inflammation, myocytolysis, necrosis) and repair (fibrosis, matrix changes); myocyte disorganization; ischemia, and other conditions. The end result is feline myocardial diseases having in common, diastolic dysfunction-specifically, left ventricular performance impaired by increased ventricular stiffness (change in pressure per unit change in volume) and its reciprocal-reduced ventricular compliance (rate of change of volume per rate of change in pressure), as well as prolonged or incomplete relaxation.


When alterations in diastolic function lead to increased LV filling pressure and mean LA pressure, pulmonary edema may result. The clinical entity of congestive heart failure (predominantly pulmonary edema) occurring in the setting of abnormal diastolic function and relatively normal systolic function has been termed diastolic heart failure. Currently, diastolic heart failure appears to represent the most common cause of symptomatic heart disease in cats, particularly in young and middle aged felines.


The Crux of the Problem

There remain substantial gaps in understanding critical issues involving the cardiomyopathies. Etiopathogenesis is unresolved. Clinical categorization of individual myocardiopathies requires refinement. Natural history must be clarified. The risk factors that predispose to subsequent events have not been identified. Moreover, substantial obstacles have resisted development of evidence based programs including issues regarding funding, logistics inherent in large prospective clinical studies, and motivation.

In absence of prospective, randomized clinical trials in cats, decisions related to drug safety and efficacy result largely from comparable human data, retrospective feline case studies, clinically derived observations of mechanisms and physiology in cats, and of course, personal experience. Because data addressing comparative drug efficacy and long-term benefit is unavailable, recommendations for therapy are unproven, and a number of important clinical questions remain to be answered: Are current therapies for diastolic heart failure comparably applicable to all subpopulations (phenotypes) with diastolic dysfunction? Can outcome be predicted using markers of myocardial injury or assays to assess neuroendocrine changes? Should diastolic heart failure therapy vary between breed/gender/age? Are certain therapies clearly optimal for chronic management? And for preventive strategies to be fully effective, would therapies have to be implemented throughout the lifetimeof an individual (and when should they be initiated)?

In order to determine the safest, most effective therapies for treating heart disease, clinicians must forge a partnership and encourage cooperation for trials which answer these type of questions. We do a great job with diagnostic ultrasound, clinical assessment, and treating acute heart failure. We need to learn how to do a better job of long term management and prevention.

Management of the Asymptomatic Cat

There is currently no evidence that treatment of asymptomatic cats prevent disease progression, reduce risk factors, or affects morbidity and mortality. Nevertheless, there are a number of circumstances in which substantial myocardial structural and functional derangement appears to promote adverse outcome, and thereby are raison d'être for pharmacologic intervention. The following may warrant therapy, although efficacy remains unproven.

Myocardial Infarction - In cats with myocardial infarction inferred by echocardiography, ACE inhibitors and beta-blockers have been used. Rationale for ACEI therapy is based upon the potential of these agents to favorably influence ventricular remodeling and reduce mortality. Rationale for beta-adrenergic blockers include reduction of infarct size, myocardial oxygen utilization, and reduced mortality. Calcium channel blockers are not recommended for use in acute infarction (humans).

Tachyarrhythmia - Rapid tachyarrhythmias can reduce cardiac filling, promote ischemia, and result in hemodynamic instability. Sustained tachyarrhythmias are usually associated with myocardial disease with attendant cardiac remodeling (myocyte necrosis, fibrosis, inflammation, and interstitial matrix changes). Therefore, it is prudent to consider antiarrhythmic therapy in selected cases, particularly when the ventricular rate is rapid.

Massive Left Ventricular Hypertrophy (Severe Hcm) - Although not confirmed, some cardiologists consider cats with greatly increased left ventricular mass (maximal diastolic septal or left ventricular wall thickness > 8mm) to be at increased risk for cardiovascular events.

Syncope - Recurrent syncope is a risk factor for sudden death in humans with HCM. In cats syncope can be associated with tachyarrhythmias, dynamic LV outflow obstruction (LVOTO), and ischemia (infarction). Symptoms can often be managed successfully with beta-blockers to reduce or abolish LVOTO.

Spontaneous Echo Contrast ("Smoke") - Spontaneous echo contrast is associated with blood stasis. This finding is considered to presage thrombosis and is associated with increased thromboembolic risk. It should therefore warrant antiplatelet drugs (aspirin) and perhaps more aggressive therapies.

"Malignant" Familial History Of Sudden Death (High Risk Genotype) - Pedigrees may be identified with a documented heritable pattern of HCM with severe morbidity and mortality (e.g., Maine coon cats, others). Early intervention with calcium channel blockers or beta-adrenergic blockers may be contemplated based on experimental considerations which hold that a pathway to the phenotypic expression of LV hypertrophy is influenced by triggers such as higher LV pressure and work load.

Myocardial Failure - In some HCM cats LV contractility is reduced (e.g., fractional shortening, 23-29%; LV end-systolic dimension, 12-15 mm) from acute or chronic myocardial infarction, myocarditis, and other causes of LV remodeling. Therapies include oral taurine supplementation, ACE inhibitors to counteract neurohormonal activation and reduce remodeling, and judicious beta-blocker therapy if myocardial infarction is suspected or with tachyarrhythmia.

Chronic Management of Diastolic Heart Failure

Diuretic administration remains the cornerstone for acute management of pulmonary edema. While no studies have investigated the optimal diuretic dose once the patient is compensated, life-long diuretic administration is a generally accepted practice. Rationale for including supplementary drugs is based upon the belief that pharmacological intervention in the rennin-angiotensin system can improve neuroendocrine perturbations activated in the failing heart-and thereby reduce morbidity and mortality. Accordingly, the addition of beta-blockers, calcium channel blockers, and/or ACE inhibitors to diuretics are intended to improve clinical outcome and prolong survival.

Towards Evidence-Based Management

The most valued treatment outcomes include absence of clinical events, enhanced quality of life, and prolonged survival. Therefore, the foundation of evidence-based medicine is randomized clinical trials designed to evaluate effects of specific therapies on morbidity and mortality. Ideally, treatment guidelines are best developed in concert with epidemiology, natural history, and risk factor analysis. This is particularly effective when expert committees convene to review literature and incorporate the best clinical data from trials designed to substantiate evidence for treatment benefit.

There have evolved simple schemes to help assess scientific data with an evidence-based perspective. One widely held method qualifies clinical data according to four categories of evidence type (A through D) and three categories of evidence strength (Table 1). For example, when evaluating clinical data, one looks to determine the basis of stated findings (i.e., large, prospective, randomized trial vs small retrospective series)-and assess how strong the evidence is that support related contentions. Accordingly, it is instructive to view the literature through this perspective when, for example, looking to assess evidence that a given drug confers a particular treatment benefit.

An evidence-based approach is meant to shape clinical decisions utilizing the best scientific evidence currently available. Because of specific or unique patient needs, therapy for each case must ultimately be individualized.

Table 1. Categorization of Clinical Evidence

Type of Evidence

Category- Type of Evidence
Description, Type of Evidence

Large, prospective, randomized, controlled clinical trials designed to assess treatment and outcome

Smaller randomized, controlled clinical trials; Meta-analysis of other clinical trials

Studies that collect observational or metabolic/physiologic data

Clinical experience

Strength of Evidence

Category- Strength of Evidence

Very strong evidence

Moderately strong evidence

Strong trend

Future Directions

To begin to address unanswered issues regarding treatment efficacy, a multicenter collaborative clinical trial to study chronic heart failure therapies was initiated in 1998 by this author. Designed by a consensus group as a prospective, blinded, controlled study, cats recovering from first onset of diastolic heart failure are randomized into one of four treatment groups (atenolol, dilacor, enalapril, or placebo). All cats receive background therapy of low dose furosemide. At the time of this proceedings submission, the trial remains ongoing.


1. Ahmed A. ACC/AHA chronic heart failure evaluation and management guidelines: Relevance to the geriatric practice. J Am Geriatr Soc 51:123-126; 2003

2. Amberge C, Glardon O, Glaue, et al. Effects of benazepril in the treatment of feline hypertrophic cardiomyopathy, Results of a prospective, open-label, multicenter clinical trial. J Vet Cardiol 1:19-26, 1991

3. Atkins CE, Gallo AM, Kurzman ID, et al. Risk factors, clinical signs, and survival in cats with a clinical diagnosis of idiopathic hypertrophic cardiomyopathy: 74 cases (1985-1989). JAVM 201:603, 1992.

4. Baty CJ, Malarkey DE, Atkins CE, et al. Natural history of hypertrophic cardiomyopathy and aortic thromboembolism in a family of domestic shorthair cats. J Vet Int Med 15:595-596, 2001

5. Bonagura JD, Stepien RL, Lehmkuhl LB. Acute effects of esmolol on left ventricular outflow obstruction in cats with hypertrophic cardiomyopathy: A Doppler-echocardiographic study (Abstr). J Vet Int Med 5:123,1991.

6. Bright J, Golden L. Evidence for or against the efficacy of calcium channel blockers for management of hypertrophic cardiomyopathy in cats. Vet Clin N Am 21:1023, 1991

7. Bright JM, Golden L, Gompf R, et al. Evaluation of the calcium channel-blocking agents diltiazem and verapamil for treatment of feline hypertrophic cardiomyopathy. J Vet Int Med 5:272, 1991.

8. Fox PR, Liu SK, Maron B. Echocardiographic assessment of spontaneously occurring feline hypertrophic cardiomyopathy An animal model of human disease. Circulation 92:2645, 1995.

9. Fox PR. Feline Cardiomyopathies. In Fox PR, Sisson DD, Moise NS (eds): Textbook of Canine and Feline Cardiology Principles and Clinical Practice. 2nd Ed, WB Saunders, Philadelphia, 1999, p621.

10. Fox PR. Current usage and hazards of diuretic therapy. In Kirk RW, Bonagura JD (eds): Current Veterinary Therapy, Vol XI, Philadelphia, WB Saunders, 1992, p 668.

11. Fox PR. Evidence for and against beta-blockers and aspirin for management of feline cardiomyopathies. Vet Clin North Am 21:1011, 1991.

12. Golden AL, Bright JM. Use of relaxation half-time as an index of ventricular relaxation in clinically normal cats and cats with hypertrophic cardiomyopathy. Am J Vet Res 51:1352, 1990.

13. Hunt SA, Baker DW, Chin MH, et al. ACC/AHA guidelines for the evaluation and management of chronic heart failure in the adult: Executive summary. Circulation 2001:104;2996-3007

14. Johnson LM, Atkins CE, Keene BW, et al. Pharmacokinetic and pharmacodynamic properties of conventional and CD-formulated diltiazem in cats. J Vet Int Med 10:316, 1996.

15. Keene BW Towards evidence-based veterinary medicine. J Vet Intern Med 14:1180119: 2000

16. King JN, Humbert-Droz, Maurer M. Pharmacokinetics of benazepril and inhibition of plasma ACE activity in cats (Abstr). J Vet Int Med 10:163, 1996.

17. Kittleson MD, Meurs KM, Munro MJ, Kittleson JA, Liu SK, Pion PD, Towbin JA. Familial hypertrophic cardiomyopathy in Maine coon cats: an animal model of human disease. Circulation. 22;99:3172, 1999.

18. Kitzman DW, Little WC, Brubaker PH, et al. Pathophysiological characterization of isolated diastolic heart failure in comparison to systolic heart failure. JAMA. 288:2144-50;2002

19. Redfield MM, Jacobsen SJ, Burnett JC Jr, et al. Burden of systolic and diastolic ventricular dysfunction in the community: appreciating the scope of the heart failure epidemic. JAMA. 289:194-202; 2003

20. Rush JE, Freeman LM, Brown DJ, Smith FW. The use of enalapril in the treatment of feline hypertrophic cardiomyopathy. J Anim Hosp Assoc 34;38-41, 1998

21. Rush JE, Freeman LM, Fenollosa NK, et al. Population and survival characteristics of cats with hypertrophic cardiomyopathy: 260 cases (1990-1999). J Am Vet Med Assoc 220:202-207: 2002

22. Sanders N, Hamlin R, Buffington T, et al. Effects of enalapril on healthy cats (Abstr). J Vet Int Med 6:139, 1992.

23. Smith SA, Tobias AH, Jacob KA, et al. Arterial thromboembolism in cats: Acute crisis in 127 cases (1992-2001) and long-term management with low-dose aspirin in 24 cases. J Am Vet Int Med 17:73-83; 2003

24. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation, and treatment of height blood cholesterol in adults (adult treatment panel III). NIH Publication No 02-5215. Circulation 106:3142-3421, 2002

25. Vasan RS, Benjamin EJ, Levy D, et al. Prevalence, clinical features and prognosis of diastolic heart failure: an epidemiologic perspective. J Am Coll Cardiol.26:1565-1574, 1995

26. Yusuf R. Randomized controlled trials in cardiovascular medicine: past achievements, future challenges. BMJ 321:564-568; 1999

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)
Philip R. Fox, DVM, DACVIM (Cardiology)
Animal Medical Center
510 East 62nd St.
New York, NY 10021

Funding by Merial – Grant
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