Page 276 - Feline Cardiology

Chapter 19: Congestive Heart Failure 283

are stretched. Brain natriuretic peptide is normally syn- (846 pmol/l vs 53 pmol/l, P < 0.001). [NT-proBNP]
thesized as a prohormone (pre-proBNP) in the atria. greater than 265 pmol/l was highly sensitive (90%) and
However, in the presence of increased ventricular wall specific (88%) for diagnosis of heart failure in dyspneic
stress or neurohormonal stimulation (endothelin I and/ cats, although it is important that false positives may exist,
or angiotensin II), ventricular synthesis of BNP is up- and a mildly to moderately elevated [NT-proBNP] may
regulated. In healthy cats, BNP is concentrated in the occur in the presence of renal failure and reduced renal
right auricle and is present diffusely throughout the left clearance of the hormone (Connolly et al. 2008; Schmidt
atrium. It has a novel expression in the left ventricle in et al. 2009). NT-proANP appears to be less useful than
cats with hypertrophic cardiomyopathy (Biondo et al. NT-proBNP since it was not different in asymptomatic
2003). Activation of BNP transcription is one of the cats with HCM compared to normal control cats
earliest and most reliable markers of ventricular cardio- (MacLean et al. 2006) (see Chapter 8 for greater detail).
myocyte hypertrophy (Liang et al. 2001). Ventricular Plasma [BNP] has also been used to predict a patient’s
BNP secretion also increases with increasing severity of response to treatment and assess prognosis in human
left ventricular dysfunction (Yasue et al. 1994). Upon medicine (Bettencourt et al. 2002; Cheng et al. 2001;
secretion, pro-BNP is cleaved into an inactive fragment Troughton et al. 2000; Koglin et al. 2001). Serial plasma
amino-terminal proBNP (NT-proBNP) and BNP. NT- [BNP] measurements of hospitalized human patients
proBNP has a longer circulating half-life than the bio- with CHF have been shown to predict treatment outcome
logically active BNP molecule. and mortality (Bettencourt et al. 2002; Cheng et al. 2001).
Measurement of plasma [ANP], [BNP], and [NT- Patients whose plasma [BNP] declined during hospital-
proBNP] is a useful method for diagnosis of heart disease ization were much less likely to be rehospitalized or die
and heart failure in people, dogs, and cats (Maisel et al. than patients whose plasma [BNP] increased during hos- Congestive Heart Failure
2003; Fine et al. 2008; Boswood et al. 2008; DeFrancesco pitalization (Bettencourt et al. 2002; Cheng et al. 2001).
et al. 2007; Prosek et al. 2007; Fox et al. 2009). Using a Optimal reevaluation period for plasma [BNP] was 7
rapid point-of care-assay, plasma [BNP] is highly sensi- days following heart failure treatment in a human study
tive for diagnosis of systolic heart failure (e.g., DCM) (Wu et al. 2004). In one study, when diuretic therapy of
(95%) and diastolic heart failure (e.g., HCM or RCM) CHF was guided by plasma NT-BNP, there were fewer
(86%) in people, and is an essential tool to help differenti- cardiovascular events and the time to the first event was
ate primary respiratory disease versus heart failure as a delayed compared to treatment using standard clinical
cause of dyspnea (Maisel et al. 2003). People with systolic criteria (Troughton et al. 2000). Patients with BNP-
heart failure had significantly higher plasma [BNP] than guided treatment received higher diuretic doses than
people with diastolic heart failure (812 pg/ml vs 413 pg/ patients treated in the standard clinical manner (Troughto
ml, respectively, P < 0.001), which may be due to greater et al. 2000). Future veterinary studies are needed to evalu-
ventricular wall stress with dilated cardiomyopathy ate plasma [BNP] during treatment of CHF, evaluate it as
(Maisel et al. 2003). In a small pilot study of cats, plasma a prognostic indicator of early cardiovascular mortality,
[BNP] and [NT-ANP] were elevated in asymptomatic and assess whether measurement of plasma [BNP] can be
cats with cardiomyopathy and were further elevated used to help tailor medical treatment of CHF. Currently,
in cats with CHF or arterial thromboembolism (normal NT-proBNP is the most promising feline cardiac bio-
cats: mean plasma [BNP] = 11.6 pg/ml and [NT- marker for identifying and monitoring cats with conges-
proANP] = 0.54 pmol/ml; asymptomatic: mean plasma tive heart failure. Its role appears to be one that
[BNP] = 98 pg/ml and [NT-proANP] = 0.83 nmol/ml; heart complements, but does not replace, the traditional cor-
failure/ATE: mean plasma [BNP] = 185 pg/ml and plasma nerstones of diagnosis: history, physical exam, thoracic
[NT-proANP] = 2.3 nmol/ml), although significant radiography, and echocardiography.
overlap existed between the groups (Sisson et al. 2003).
BNP appears to have a greater diagnostic potential than Troponin I
ANP given its greater degree of elevation (10-fold increase Cardiac troponin I is released when there is cardiomyo-
for BNP versus 4–5-fold increase for ANP) in cardiac cyte damage. Serum cardiac troponin I (cTnI) has been
disease and CHF in cats (Sisson 2004). A commercially studied in cats with cardiomyopathy and heart failure,
available ELISA test measuring the inactive fragment and has been shown to be a sensitive biomarker for heart
NT-proBNP has been evaluated in 68 dyspneic cats, and failure in cats (sensitivity 87%, specificity 84%), but does
it was useful to discriminate between cats with congestive not distinguish symptomatic cats from asymptomatic
heart failure (CHF) and cats with primary respiratory cats (Connolly et al. 2003). Another study found contra-
disease. Cats with CHF had significantly higher [NT- dictory results, where cTnI was increased in asymptom-
proBNP] than cats with primary respiratory disease atic cats with cardiomyopathy and was further increased