The Companion Times News | Updates | Insights | Reviews | Developments Volume 3. Issue - 2020II APR MAY- A bi-monthly scienti? c newsletter brought to you as part of the Educational Initiative of SAVAVETs part of the Educational Initiative of SAVAVET a

Namaste! We are back again! We are pleased to bring a special editon in Small Animal Cardiology in the current issue of The Companion Times, As a busy practitioner, you will ? nd this issue informative and interesting. Go an and read your heart’s full ! IN THIS ISSUE 03 2019 ACVIM CARDIOLOGY CONSENSUS GUIDELINES 04 2009 ACVIM STAGING SYSTEM FOR MMVD 10 EVERY MURMUR MATTERS. HOWEVER FEEBLE. 13 IS TRIPLE THERAPY INCLUDING ACEI SUPERIOR TO DOUBLE THERAPY IN MMVD? 19 CARDIORENAL Your contributions are invited for the upcoming Newsletters. Kindly send them to [email protected] SYNDROME TYPES 20 AETIOLOGY OF CvRD IN DOGS & CATS 22 PIMOBENDAN IN CATS WITH HYPERTROPHIC CARDIOMYOPATHY (HCM)

2019 ACVIM CARDIOLOGY CONSENSUS GUIDELINES THE RECOMMENDATIONS FOR DIAGNOSIS AND TREATMENT OF “ “ STAGE A REMAINS UNCHANGED IN THE NEWLYREVISED GUIDELINES . Management of MMVD DIAGNOSISOF STAGE A Management of MMVD before the onset of  Small breed dogs, including breeds with before the onset of clinical signs of heart clinical signs of heart known predisposition to develop MMVD failure has changed failure has changed (eg, Cavalier King Charles Spaniels, substantially compared substantially compared with the 2009 guidelines. Dachshunds, Miniature, and Toy Poodles) with the 2009 guidelines. should undergo regular evaluations (yearly “ “ auscultation by the family veterinarian) as part of routine health care. (Class I, LOE : expert opinion) TREATMENTOF STAGE A  Owners of breeding dogs or those at  No drug treatment recommended for any especially high risk, such as Cavalier King patient. (Class I, LOE : expert opinion) Charles Spaniels, may choose to participate  No dietary treatment recommended for any in yearly screening events at dog shows or patient. (Class I, LOE : expert opinion) other events sponsored by their breed  Potential breeding animals should no longer association or yearly screening events at dog be bred if a murmur or echocardiographic shows or other events sponsored by their evidence of mitral regurgitation (MR ) is breed association or kennel club and identi? ed early, during the normal breeding conducted by board-certi? ed cardiologists age range (<6-8 years of age). (Class I, parti cipating in an - ACVIM -approved LOE: moderate) disease registry. (Class I, LOE : expert opinion) et al. ACVIM Keene BW , Haggstrom J, Atkins CE consensus guidelines for the diagnosis and treatment of myxomatous mitral valve disease in dogs. J Vet Int Med. 2019;33:1127-1140 Apr - May 2020 03

2009 ACVIM STAGING SYSTEM FOR MMVD STAGE A Identi? es dogs at high risk for developing heart disease but that currently have no identi? able structural disorder of the heart (eg, every Cavalier King Charles Spaniel or other predisposed breed without a heart murmur). STAGE B Identi? es dogs with structural heart disease (eg, the typical murmur of mitral valve regurgitation, accompanied by some typical valve pathology, is present), but that have never developed clinical signs caused by heart failure. STAGE B1 Describes asymptomatic dogs that have no radiographic or echocardiographic evidence of cardiac remodeling in response to their MMVD, as well as those in which remodeling changes are present, but not severe enough to meet current clinical trial criteria that have been used to determine that initiating treatment is warranted. STAGE B2 Refers to asymptomatic dogs that have more advanced mitral valve regurgitation that is hemodynamically severe and long-standing enough to have caused radiographic and echocardiographic ? ndings of left atrial and ventricular enlargement that meet clinical trial criteria used to identify dogs that clearly should bene? t from initiating pharmacologic treatment to delay the onset of heart failure. STAGE C Denotes dogs with either current or past clinical signs of heart failure caused by MMVD . Because of important treatment differences between dogs with acute heart failure requiring hospital care and those in which heart failure can be treated on an outpatient basis, these issues have been addressed separately by the panel. It is important to note that some dogs presented with heart failure for the ? rst time may have severe clinical signs requiring aggressive treatment (eg, with additional afterload reducers or temporary ventilatory assistance) that more typically would be reserved for those patients refractory to standard treatment (see Stage D below). STAGE D Refers to dogs with end-stage MMVD , in which clinical signs of heart failure are refractory to standard treatment. Such patients require advanced or specialized treatment strategies to remain clinically comfortable with their disease, and at some point, treatment efforts become futile without surgical repair of the valve. 04 Apr - May 2020

STAGE B DOGS HAVE A STRUC-  No drug or dietary treatment is recom- TURAL ABNORMALITY EG THE ( , mended (Class I, LOE: expert opinion) ) PRESENCE OF MMVD BUT HAVE NEVER HAD CLINICAL SIGNS OF  Re-evaluation by echocardiography is sug- HEART FAILURE ASSOCIATED gested (or radiography if echocardiography WITH THEIR DISEASE . is unavailable) in 6-12 months, depending MMVD is recognized during a screening or on the imaging results (some panelists routine health examination by auscultation of recommend more frequent follow-up in a heart murmur typical of mitral valve large dogs). (Class I, LOE: expert opinion) regurgitation. Stage B2 dogs have asymptomatic MMVD  Thoracic radiography is recommended in Dogs in this category should meet the criteria all patients to assess the hemodynamic outline below: relevance of the valve disease and to obtain  Murmur intensity =3/6 baseline thoracic radiographs at a time  Echocardiographic LA: Ao ratio in the when the patient is asymptomatic for right-sided short axis view in early diastole MMVD. (Class I, LOE: expert opinion). =1.6  Left ventricular internal diameter in  Blood pressure measurement is diastole, normalized for body weight recommended for all patients to identify or (LVIDDN) =1.7 rule out concurrent systemic hypertension  Breed-adjusted radiographic vertebral heart and to establish baseline blood pressure. score (VHS) >10.5 (Class I, LOE : expert opinion)  Echocardiography is recommended to de? nitively identify the cause of the murmur, answer speci? c questions regarding the severity of cardiac chamber enlargement, and identify comorbidities. (Class I, LOE : Moderate). The recommendations for treatment and “ Dogs in Stage B2 are likely monitoring of Stage B1 remain unchanged to bene? t substantially from the earlier recommendations Treatment is not recommended in these dogs from treatment before the because at this early stage of disease, onset of clinical signs of heart failure. progression to heart failure is uncertain, (Class I, LOE: Strong). unlikely to occur within the recommended “ evaluation interval, and there is no evidence that medication is effective at this stage. Apr - May 2020 05

TREATMENT FOR STAGE B2  Surgical intervention in advanced Stage B2  Pimobendan is recommended at a dosage is possible and recommended by some of 0.25-0.3 mg/kg PO q12h.44,55 (Class I, panelists for clients who can afford and LOE: strong) access mitral valve repair at the few centers demonstrating evidence of acceptably low  Dietary treatment is recommended that includes mild dietary sodium restriction, complication rates and effective, durable provision of a highly palatable diet with results. (Class IIa, LOE: moderate) adequate protein and calories for maintaining optimal body condition. (Class IIa, LOE: weak)  For patients in Stage B2 on either initial Coughing in dogs: what is examination, or in which the LA has the evidence for and increased markedly in size on successive against a cardiac cough? monitoring examinations, 5 (of 10) Ferasin L and Linney C. JASP. 2019; Vol 60: 139-145 Dogs with CHF may cough, but panelists recommend treatment with ACEI. the cause may not always be (Class IIa in geographic regions where pulmonary oedema, and other ACEI are low cost, LOE: weak) Clinical features of the cardiac disease or trials addressing the ef? cacy of ACEI for concurrent lower airway disease are likely to play a part in the treatment of dogs in Stage B have shown “cardiac cough.” mixed results. Lethargy, exercise intolerance and  Beta blockade is not recommended tachypnoea/dyspnoea are much routinely to delay the onset of heart failure more speci? c signs of left-sided in dogs in Stage B2, regardless of heart CHF. enlargement. (Class III, LOE: weak) Coughing should continue to remain listed as a clinical sign of  Spironolactone is not recommended for CHF but in isolation it has a low routine use to delay the onset of heart speci? city for heart disease and failure in dogs. (Class IIb, LOE: expert clinicians should not rely on this opinion). clinical sign to diagnose heart disease or heart failure.  Some panelists ? nd the use of cough Cough in the absence of suppressants useful in occasional patients in tachypnoea and/or dyspnoea is advanced Stage B2 when their cough is most likely a feature of primary thought to be the result of pressure from respiratory disease rather than a cardiac enlargement (without pulmonary cardiac disease. edema) on adjacent bronchi. (Class IIa, LOE: expert opinion) 06 Apr - May 2020

DIAGNOSIS OF STAGE C The signalment, history, and physical examination can be helpful in determining the pretest probability of heart failure as a cause of clinical signs in patients with MMVD. For example, obese dogs with no history of weight loss are less likely to be in heart failure secondary to MMVD; dogs with marked sinus arrhythmia and relatively slow heart rates also are less likely to have clinical signs attributable Worsens with time and has an to MMVD than are those with similar clinical asymptomatic phase and symptomatic phase. During the signs (eg, cough, dyspnea) with sinus rhythm asymptomatic phase, the dog or sinus tachycardia. (Class I, LOE: expert exhibits no signs of CHF apart opinion) from a heart murmur. The typical dog in Stage C from MMVD PROGRESSIVELY presents with clinical signs of left-sided CHF DEGENERATING and a history that can include tachypnea, LESIONS restlessness, respiratory distress, or cough. Because of the relatively high prevalence of chronic tracheobronchial disease in the MITRAL population most at risk for MMVD, the REGURGITATION presence of a typical left apical regurgitant quality murmur in a coughing dog does not necessarily mean that clinical signs are the INCREASED VOLUME result of CHF. A clinical database (including LOAD ON THE LEFT SIDE OF HEART thoracic radiographs and ideally an echocardiogram) should be obtained. Additionally, basic laboratory tests, including at a minimum PCV as well as serum total CARDIOMEGALY protein, creatinine, urea nitrogen and electrolyte concentrations, and urine speci? c gravity) should be obtained as soon as practical in dogs with heart failure. Impaired renal CHF function in particular represents an important comorbidity in dogs with heart failure. (Class I, LOE: expert opinion) Apr - May 2020 07

Echocardiography with Doppler studies Acute (hospital-based) treatment of Stage C also is useful in the diagnosis of dogs with  Furosemide 2 mg/kg administered IV (or MMVD that have advanced to Stages C and D. intramuscularly [IM]), followed by 2 mg/kg Cardiac ultrasound examination can con? rm IV or IM hourly until the patient's respira- the presence of MMVD, quantify chamber tory signs are substantially improved (ie, enlargements and cardiac function, provide respiratory rate and effort are decreased) or general estimates of LV ? lling pressures, and a total dosage of 8 mg/kg has been reached identify comorbidities and complications of over 4 hours. (Class I, LOE: expert opinion) chronic MR. These might include pulmonary  For life-threatening pulmonary edema (ie, hypertension, acquired atrial septal defect, and expectoration of froth associated with pericardial effusion from an atrial tear or severe dyspnea, radiographic white-out unrelated cardiac tumor. In dogs with evidence lung, poor initial response to furosemide of symptomatic pulmonary hypertension (eg, bolus with failure of respiratory effort and exertional fatigue, collapse or syncope, ascites rate to improve over 2 hours), furosemide from right-sided CHF), spectral Doppler also may be administered as a constant rate ? ndings can substantiate the diagnosis and infusion (CRI) at a dosage of 0.66-1 help guide therapeutic decision-making. mg/kg/ hour after the initial bolus.66,67 As a group, dogs with clinical signs caused (Class IIa, LOE: weak) by heart failure have higher serum NT-  Allow the patient free access to water once proBNP concentrations than do dogs in diuresis has begun. (Class I, LOE: expert which clinical signs are caused by primary opinion; humane considerations apply) pulmonary disease.  Pimobendan, 0.25-0.3 mg/kg admini- A normal or near normal NT-proBNP stered PO q12h. The recomme ndation to - concentration in a dog with clinical signs of use pimobendan in acute heart failure cough, dyspnea, or exercise intolerance treatment is strongly supported by strongly suggests that heart failure is not the hemodynamic and experimental evidence cause of the clinical signs. (Class I, LOE: as well as the anecdotal experience of the moderate) panelists. In many countries outside of the Most symptomatic dogs with MMVD are United States, pimobendan for IV middle-aged or older, and it is prudent to administration is available. (Class I, LOE: complete the clinical database with a blood weak) pressure assessment, CBC, serum biochemical  Oxygen supplementation, if needed, can pro? le, and urinalysis, especially if treatment be administered via a humidity and tempe- for CHF is anticipated. (Class I, LOE: expert rature controlled oxygen cage or incubator opinion) or via a nasal oxygen cannula. (Class I, LOE: expert opinion) 08 Apr - May 2020

 Mechanical treatments (eg, abdominal comfort care measures. Continuous ECG paracentesis, thoracentesis) are recomm- monitoring is recommended where ended to relieve effusions judged suf? cient available during dobutamine infusion, with to impair ventilation or cause respiratory dosage reduction indicated if tachycardia or distress. (Class I, LOE: expert opinion) ectopic beats occur. (Class I, LOE: expert  Sedation-anxiety associated with opinion) dyspnea should be treated. Narcotics, or  Constant IV infusion of sodium nitro- a narcotic combined with an anxiolytic prusside at dosages ranging from 1 to 15 agent, most often are used by panelists. Care ìg/kg/min) for up to 48 hours often is must be taken to monitor the blood useful for lifethreatening, poorly responsive pressure and respiratory response to pulmonary edema69; this medication is narcotics and tranquilizers. No speci? c currently (2018) expensive in the United treatment or dosage regimen was used by all States. panelists. Butorphanol 0.2 to 0.25 mg/kg  Although ACEI is a Class I recommen- administered IM or IV was the narcotic dation for chronic Stage C heart failure and most often utilized for this purpose; some panelists also treat acute heart failure combinations of buprenorphine (0.0075- with ACEI, the evidence supporting 0.01 mg/kg) and acepromazine (0.01-0.03 ACEI ef? cacy and safety in acute mg/kg IV, IM, or SC) as well as other narco- treatment, when combined with tics, including morphine and hydrocodone, furosemide and pimo bendan, is less - also were suggested. (Class I, LOE: expert clear. opinion)  Provide optimal nursing care, including maintenance of appropriate environmental temperature and humidity, increase of the “ head on pillows, and placement of sedated patients in sternal posture. (Class I, LOE: expert opinion) Emerging data from  Dobutamine (2.5-10 /kg/min as a CRI, ìg VALVE Study opens up an exciting debate on the starting at 2.5 ìg /kg/min and increasing value of adding ACEI to the dosage incrementally) may be used in Pimobendan and addition to the above treatments to improve Furosemide in patients the left ventricular function in patients that with MMVD. “ fail to respond adequately to diuretics, pimobendan, sedation, oxygen, and Apr - May 2020 09

1. Focal and dif? cult to hear. Requires careful listening in a quiet environment 2. Quiet but immediately audible over the point of maximum intensity. Softer than heart sounds. 3. Moderately loud. Same intensity as S1 and S2 heart sounds. 4. Louder than heart sounds. No palpable precordial thrill. Often obscures S2 heart sound Audible over a wide area. 5. Loud with a palpable precordial thrill. 6. Loud murmur with palpable precordial thrill. Audible with stethoscope chest piece held slightly off chest well. MOST LIKELY TO HAVE CARDIOMEGALY 10 Apr - May 2020

There is, however, clear evidence that the  Chronic PO furosemide dosages =8 acute administration of enalapril plus mg/kg q24h in any dosing regimen (or the furosemide in acute heart failure results in equipotent torsemide dosage) needed to signi? cant improvement in pulmonary maintain patient comfort in the face of capillary wedge pressure when compared appropriate dosages of pimobendan, an with the admini stration of furosemide - ACEI, and spironolactone indicate disease alone. (Class IIb, LOE: weak) progression to Stage D. (Class I, LOE: weak)  Nitroglycerin ointment, approximately  Measurement of serum creatinine, blood half an inch paste/10 kg BW, applied to an urea nitrogen, and electrolyte concen- unhaired or shaved area of skin, can be used trations 3-14 days after initiating furose- for the ? rst 24 to 36 hours of hospitali- mide treatment is recommended for zation. 71,72 Some panelists recommend animals with Stage C heart failure. (Class I, administering the ointment at intervals (12 LOE: weak) hours on, 12 hours off). (Class IIb, LOE: weak)  Continue or start ACEI (eg, enalapril or Chronic(home-based)treatment of StageC benazepril, 0.5 mg/kg PO q12h) or an equivalent dosage of another ACEI, if approved for this use.  Measurement of serum creatinine and electrolyte concentrations 3-14 days after beginning an ACEI is recomm- ended for animals with Stage C heart failure. Concern for development of acute kidney injury is warranted should serum creatinine concentrations increase by =30%  Continue PO furosemide admini- of the baseline concentration. (Class I, stration to effect, commonly at a dosage of LOE: weak) 2 mg/kg administered q12h, or as needed to maintain patient comfort. Some panelists  Spironolactone (2.0 mg/kg PO q12 - 24 h) now choose to substitute torsemide for is recommended as an adjunct for chronic furosemide at 1/10-1/20 or approximately treatment of dogs in Stage C heart failure. 5% to 10% of the furosemide dosage, or The primary bene? t of spironolactone in approximately 0.1-0.3 mg/kg q24h73 for this situation is thought to be aldosterone home care in animals in which hospitalized antagonism.(Class I, LOE: moderate) CHF management using furosemide was  Continue pimobendan, 0.25-0.3 mg/kg dif? cult or met with limited success. (Class PO q12h. (Class I, LOE: strong) I, LOE: moderate) Apr - May 2020 11

 Panelists recommend against starting a beta combination with diltiazem. (Class IIb, blocker in the face of active clinical signs LOE: moderate) of CHF (eg, cardiogenic pulmonary edema)  In patients receiving a beta blocker before caused by MMVD. (Class IV, LOE: weak) the onset of Stage C heart failure, the  None of the panelists routinely use majority of panelists continue beta nitroglycerin in the chronic treatment of blockade; some panelists consider dosage Stage C heart failure. (Class III, LOE: reduction if needed clinically because of expert opinion) clinical signs of low cardiac output,  Home-based care to promote ideal BW, hypothermia, or bradycardia. (Class IIB, appetite, respiratory and heart rate LOE: expert opinion) monitoring while providing client support  Some panelists ? nd the use of cough to enhance medication regimen adherence suppressants useful in occasional patients and dosage adjustments in patients with in Stage C heart failure from MMVD. (Class heart failure is encouraged. (Class I, LOE: IIa, LOE: expert opinion) expert opinion).  Some panelists ? nd the use of broncho-  Identi? cation of increases in resting dilators useful in occasional patients in respiratory rate above normal baseline has Stage C MMVD patients. (Class IIb, LOE: the best predictive value for impending expert opinion) clinical decompensation. (Class I, LOE: moderate).  In centers with low complication rates, Stage C patients bene? t from surgical intervention to repair their mitral valve apparatus. (Class I, LOE: moderate)  In cases complicated by atrial ? brillation, diltiazem, often in combination with digoxin (see below), is recommended to control ventricular rate. (Class I, LOE: moderate)  For the chronic management of Stage C heart failure, panelists recommended the addition of digoxin only in cases complicated by persistent atrial ? brillation to slow the ventricular response rate. In these cases, digoxin generally is used in 12 Apr - May 2020

Game-changingVALVE Study First study to evaluate prospectively the result of adding ACE-Inhibitor to Pimobendan + Furosemide with a long follow-up period. Key Question: Study Population: 158 dogs, 77 in dual therapy Is Triple Therapy (Pimobendan+ Furosemide) Superior to Double and 79 in triple therapy (Pimobendan+ Furosemide) Therapy in MMVD ? + ACE -I) with similar baseline characteristics. No apparent bene? t in combining ACE inhibitor on top of pimobendan and furosemide in dogs with CHF due to MMVD. 223 days 100 Median survival Time 80 in Dual Therapy (Pimobendan+ 60 Furosemide) 40 179 days Median survival Time in 20 Triple Therapy Pimobendan (Furosemide + Ramipril) 0 + 0 250 500 750 1000 1250 1500 1750 Time (days) Vasotop in Addition to Lasix and Vetmedin for the treatment of mitral valve Endocardiosis. G Wess. On behalf of the VALVE Investigators 158 dogs, 77 in dual therapy (Pimobendan + Furosemide) and 79 in triple therapy (Pimobendan + Furosemide + ACE-I) with similar baseline characteristics. Apr - May 2020 13

Dietary treatment for Stage C food, and foods used to administer  Cardiac Cachexia has substantial negative medications) and avoid any processed or prognostic implications and is much easier other salted foods.(Class I, LOE: moderate) to prevent than to treat. (Class I, LOE:  Monitor serum electrolyte concentrations moderate) and supplement the diet with potassium  Maintain adequate calorie intake to from either natural or commercial sources minimize weight loss that often occurs in only if hypokalemia is identi? ed. (Class I, CHF. Simple culinary strategies to improve LOE: expert opinion) appetite may be bene? cial in accomplishing  Diets and foods with high potassium this goal (eg, warming food, mixing wet content should be avoided when food with dry food, offering a variety of hyperkalemia is present. (Class I, LOE: foods). (Class I, LOE: moderate) • expert opinion)  Record body condition score and accurate  Consider monitoring serum magnesium weight of the patient at every clinic visit and concentrations, especially as heart failure investigate the cause of clinically relevant progresses and in dogs with arrhythmias. changes in body condition, weight gain or Supplement with magnesium in cases in loss. (Class I, LOE: expert opinion) which hypomagnesemia is identi? ed. (Class  Ensure adequate protein intake and avoid IIa, LOE: expert opinion) low-protein diets unless severe concurrent  Consider supplementing with omega-3 renal failure is present. (Class I, LOE: moderate) fatty acids, especially in dogs with  Modestly restrict sodium intake, taking into decreased appetite, muscle loss, or consideration sodium dog food, treats, table arrhythmia.86 (Class IIa, LOE: moderate) 14 Apr - May 2020

Acute (hospital-based) treatment of Stage D medications to have an effect, and in  In the absence of severe renal insuf? ciency providing time for left atrial dilatation to (eg, serum creatinine concentration >3 accommodate sudden increases in mitral mg/dL), additional furosemide can be valve regurgitant volume in patients with administered to dyspneic patients acute exacerbation of MMVD and diagnosed with refractory heart failure as an impending respiratory failure. (Class I, initial 2 mg/kg IV bolus followed by either LOE: weak) additional bolus doses or a furosemide CRI  In patients that can tolerate it, more at a dosage of 0.66-1 mg/kg/h, until vigorous afterload reduction (arterial respiratory distress (rate and effort) has vasodilation) is recommended, with close decreased, or for a maximum of 4 hours. monitoring of arterial blood pressure. In (Class I, LOE: expert opinion) dogs judged to be too sick to wait for the  Torsemide, a potent long-acting loop effects of PO afterload reduction or diuretic may be used to treat dogs no longer inotropic support (eg, pimobendan with or adequately responsive to furosemide (0.1- without hydralazine or amlodipine), the 0.2 mg/kg q12h-q24h or approximately administration of a CRI IV of sodium 5%-10% of the current furosemide dosage nitroprusside (for afterload reduction) or to deliver a furosemide-equivalent dose).28 dobutamine (for inotropic support, It appears that the diuresis induced by especially in hypotensive patients) or both is torsemide recommended by a majority of panelists.  Produces less renin-angiotensinaldosterone  Both are started at dosages of 1.0 system activation than more frequent what ìg/kg/min and up-titrated every 15-30 has been shown in dogs and horses with the minutes to a maximum of approximately diuresis induced by furosemide CRI.89,90 10-15 /kg/min. These rates may be used ìg Clinicians should continue to allow patients for 12-48 hours to improve hemodynamic free access to water, once diuresis has status and control refractory cardiogenic begun. (Class I, LOE: expert opinion) pulmonary edema. Continuous ECG and blood pressure monitoring are recom-  Cavitary centesis (abdominal paracentesis, thoracentesis), as needed to relieve mended to minimize the potential risks of respiratory distress or discomfort. (Class I, this treatment. (Class IIa, LOE: weak) LOE: expert opinion)  Potentially bene? cial PO drugs that decrease afterload in this situation include  In addition to oxygen supplementation as in Stage C (above), mechanical ventilatory hydralazine (0.5-2.0 mg/kg PO, starting at a assistance may be useful in making the low dosage and titrating to effect as patient comfortable, in allowing time for described above with nitroprusside, but Apr - May 2020 15

with hourly dosage increases or amlodipine evident pulmonary in? ltrates. (Class I, (approximately 0.05-0.1 mg/kg PO, also to LOE: moderate) effect, although maximal drug effect does  The occurrence of ascites or jugular not occur for approximately 3 hours, distension in patients with primarily left- mandating a slower titration). (Class I, sided heart disease is suggestive of LOE: expert opinion) pulmonary hypertension and should  These drugs are recommended in addition prompt an attempt to conclusively diagnose to an ACEI and pimobendan. Vigilance is and identify patients that may bene? t from needed to avoid serious, prolonged sildena? l. (Class IIa, LOE: weak) hypotension (monitor blood pressure  Pimobendan dosage may be increased (off- closely, maintaining arterial systolic blood label use) to include a third 0.3 mg/kg daily pressure >85 mm Hg, or mean arterial PO dose (ie, 0.3 mg/kg PO q8h); some blood pressure >60 mm Hg). Serum panelists administer an additional dose of creatinine concentration should be pimobendan on admission to Stage D reevaluated no more than 24 to 72 hours patients with acute pulmonary edema after initiating these drugs. The panel regardless of the timing of the last dose emphasized that because afterload given at home. (Class IIa, LOE: expert reduction may increase cardiac output opinion) substantially in the setting of severe MR and  Some panelists recommend adjunctive heart failure, administration of an effective treatment with bronchodilators in treating arterial dilator drug in this setting does not cardiogenic pulmonary edema in necessarily compromise blood pressure. hospitalized patients. (Class IIb, LOE: (Class IIa, LOE: expert opinion). expert opinion)  Sildena? l, (starting at 1-2 mg/kg PO q8h, and titrating if needed) is used by panelists to treat Stage D heart failure from MMVD that is complicated by clinically relevant estimated pulmonary hypertension.  Pulmonary hypertension is recognized as an increasingly frequent complication of MMVD, either as a direct consequence of severe mitral valve regurgitation or as an independent comorbidity that can be responsible for clinical signs including syncope, cough, and shortness of breath (dyspnea), and sometimes radiographically 16 Apr - May 2020

Chronic (home-based) Stage D treatment  Pimobendan dosage is increased by  Furosemide (or torsemide) dosage should some panelists to include a third 0.3 be increased as needed to decrease the mg/kg daily dose (off-label use; routine accumulation of pulmonary edema or body explanations and cautions to the owner cavity effusions, if not limited by renal apply as in hospital care described dysfunction above) or an even higher dosage when repeated rescue is necessary. (Class IIa,  Torsemide, a potent and longer-acting loop diuretic, may be used to treat dogs no LOE: expert opinion) longer adequately responsive to furosemide  Additional afterload reduction, using either (torsemide beginning dosage of 0.1-0.2 amlodipine or hydralazine may provide mg/kg PO, or approximately 5%-10% of additional hemodynamic bene? t and the current furosemide dosage, up to decrease cough frequency. approximately 0.6 mg/kg, divided q12h if  Digoxin, at the same (relatively low) necessary).94 (Class I, LOE: moderate) dosages recommended by some panelists  Spironolactone, if not already started as for Stage C heart failure with atrial recommended in Stage C, is indicated for ? brillation, is recommended for the chronic treatment of Stage D patients.74 treatment of atrial ? brillation in Stage D (Class I, LOE: moderate) patients lacking a concrete contraindi- cation. (Class IIb, LOE: moderate)  Beta blockers generally should not be initiated at this stage, unless they are being  Sildena? l (1-2 mg/kg PO q8h) may be used as an adjunct to control heart rate in useful in the management of patients with atrial ? brillation. (Class IV, LOE: expert clinical signs related to exertion and in opinion) management of ascites when there is echocardiographic evidence of moderate to  Hydrochlorothiazide was recommended by several panelists as adjunctive treatment severe pulmonary hypertension. (Class IIa, to furosemide or torsemide, utilizing LOE: weak) various dosing schedules (including  Beta blockade may be useful in decreasing intermittent use every 2nd-4th day). Some the ventricular response rate in atrial panelists warned of the risk of acute kidney ? brillation after stabilization and digitali- insuf? ciency and marked electrolyte zation, but caution should be used because disturbances, based on personal experience. of the negative inotropic effects of beta (Class IIb, LOE: expert opinion) blockers. (Class IIb, LOE: expert opinion) Apr - May 2020 17

 The majority of panelists felt that beta blockade initiated previously should not be stopped, but that dosage reduction may be needed if shortness of breath cannot be controlled by the addition of other The connection between medications or if bradycardia, hypotension, kidneys and heart has or both were present. (Class IIb, LOE: gained increasing interest. This phenomenon termed expert opinion) as “Cardiorenal Syndrome”  Cough suppressants are recommended to is based upon clinical and treat chronic, intractable cough in Stage D epidemiological home care patients by some panelists. (Class observations that both IIa, LOE: expert opinion) kidney failure and heart failure (HF) are associated  Bronchodilators are recommended to with a high incidence of treat chronic, intractable coughing in Stage failure of the other organ. D home care patients by some panelists. (Class IIb, LOE: expert opinion) 18 Apr - May 2020

ACUTE CARDIORENAL SYNDROME 1 CvRD Acute impairment of the cardiac function leading to acute H kidney injury (AKI) unstable Acute heart failure, Cardiogenic shock 2 CHRONIC CARDIORENAL SYNDROME Chronic heart failure leading to CKD CvRD H stable Chronic Heart Failure “Congestive nephropathy” ACUTE NEPHROCARDIAC SYNDROME 3 CvRD Acute primary worsening of kidney function that leads to K cardiac dysfunction unstable AKI; Hyperkalemia, uremia 4 CHRONIC NEPHROCARDIAC SYNDROME Primary CKD that contributes to cardiac dysfunction CvRD K unstable Chronic glomerular disease, anemia, systemic hypertension SECONDARY CARDIORENAL SYNDROME 5 CvRD Cardiac and renal dysfunction secondary to an acute or O chronic systemic condition Diabteic mellitus, Sepsis CvRD – Cardiovascular Renal Disease CvRDH - refers to kidney injury or dysfunction emanating from a primary disease process involving the cardiovascular system CvRDK refers to cardiovascular injury or dysfunction emanating from a primary disease process involving the kidney CvRDO refers to kidney and cardiovascular injury or dysfunction emanating from either a primary disease process outside the two systems or instances in which primary kidney and cardiovascular diseases coexist Each category is further subdivided into stable disease (S) or unstable disease (U) based on the patient’s clinical presentation. Orvalho JS and Cowgill LD. Cardiorenal Syndrome: Diagnosis and Management. Vet Clinics of North America: Small Animal Practice. 2017: 47(5): 1083-1102 Apr - May 2020 19

AETIOLOGY OF CvRD IN DOGS & CATS CvRD class Aetiology CvRDH - Systemic hypertension leading to glomerular disease - Cardiac shock, low cardiac output and systemic hypotension leading to decreased renal perfusion, azotaemia and acute kidney injury Systemic arterial thromboembolism leading to renal infarction Heartworm infection or caval syndrome leading to glomerulonephritis or AKI, respectively - Passive congestion of the kidney during heart failure* CvRDK - Kidney-mediated systemic hypertension leading to increased afterload, left ventricular hypertrophy, worsening mitral or aortic insuf? ciency, arrhythmias, vasculopathy or retinopathy - Volume overload leading to congestion or systemic hypertension Hypokalaemia or hyperkalaemia leading to cardiac arrhythmias Reduced renal clearance of drugs (e.g. digoxin) leading to toxicity Uraemic hypodipsia, anorexia or emesis leading to volume depletion and reduced cardiac output and perfusion Uraemic pericarditis Activation of the renin-angiotensin-aldosterone axis leading to sodium and water retention, cardiac and vascular remodelling or congestion - Anaemia secondary to chronic kidney disease leading to volume overload and reduced cardiac tissue oxygenation* CvRDO - Septic or neoplastic emboli leading to renal and cardiac infarction Gastric dilation and volvulus leading to cardiac arrhythmias and azotaemia - Infectious disease (e.g. Trypanosoma cruzi) - Glycogen storage disease leading to glycogen deposition in the kidneys and heart - Amyloidosis leading to amyloid deposition in the kidney and cardiac tissues* *Causes that are proposed, possible or suspected Atkiins C, Polzin DJ, Moise NS et al. Cardiovascular-renal axis disorders in the domestic dog and cat: A veterinary consensus statement. JASP; 56(9):537-52 20 Apr - May 2020

HEART BETWEEN RELATIONSHIP THE UNDERLYING MECHANISMS FAILURE (HF) AND RENAL DYSFUNCTION. Blue arrows indicate pathways by which HF may lead to renal failure. Red arrows indicate pathways by which renal failure may lead to HF. Atkiins C, Polzin DJ, Moise NS et al. Cardiovascular-renal axis disorders in the domestic POSTULATED dog and cat: A veterinary consensus statement. JASP; 56(9):537-52 Apr - May 2020 21

BACKGROUND: RESULTS Pimobendan has been shown to impart a  Signi? cant increase in left atrial fractional signi? cant survival bene? t in cardio- shortening in Pimobendan group (pimo- myopathic cats who receive it as part of bendan group 41.7% ± 5.9; placebo group heart failure therapy. 36.1% ± 6.0; p = 0.04) However, use of pimobendan remains contro-  No signi? cant difference in left ventricular versial in cats with HCM due to lack of out? ow tract (LVOT) velocities between pharmacodynamic data for pimobendan in the groups (pimobendan group 2.8 m/s ± cats with HCM and due to theoretical concerns 0.8; placebo group 2.6 m/s ± 1.0) for exacerbating left ventricular out? ow tract  No signi? cant differences between the obstructions. number of cats with LVOT obstructions between groups STUDY DESIGN:  However, use of pimobendan remains controversial in cats with HCM due to lack of pharmacodynamic data for pimobendan in cats with HCM and due to theoretical concerns for exacerbating left ventricular out? ow tract obstructions.  Owners of breeding dogs or those at “ especially high risk, such as Cavalier King Charles Spaniels, may choose to participate in yearly screening events at dog shows or Pimobendan imparts a other events sponsored by their breed signi? cant bene? t in association or yearly screening events at dog LA function in cats with HCM and provides shows or other events sponsored by their evidence that pimobendan breed association or kennel club and does not signi? cantly conducted by board-certi? ed cardiologists increase systolic function participating in an ACVIM approved disease and LVOT obstructions. “ registry. (Class I, LOE : expert opinion) Oldach MS, Ueda Yu, Stern JA et al. Cardiac Effects of a Single Dose of Pimobendan in Cats With Hypertrophic Cardiomyopathy; A Randomized, Placebo-Controlled, Crossover Study. 2019. Front. Vet. Sci., February. 22 Apr - May 2020

SAFEHEART Pimobendan Chewable Tablets 1.25/5/10mg 5 years of keeping them connected. Heart to Heart. Evidence that speaks. 4000 patients with CHF & lots of heart-winning stories Because of every heart matters. Apr - May 2020 23

References: 1. David Dycus, Helpful Tips for Managing wounds in veterinary Patients. Today’s Veterinary Practice, November- December 2013. 2. Caleb Hudson, Degloving Wound Management by Second-Intention Healing. Veterinary Team Brief, October 2016. 3. Bonnie Grambow Campbell, The New Standard of Care, Moist Wound Healing. Today’s Veterinary Practice, July- August 2015. 4. Karen M. Tobias, The Essential Wound Care Series Basic Wound Care. NAVC Clinician’s Brief, March 2012 5. Elena Zubin, Regenerative therapy for the management of a large skin wound in a dog. Clinical Case Reports published by John Wiley & Sons Ltd., 2015 6. Julia P. Sumner, Dorsal skin necrosis secondary to a solar-induced thermal burn in a brown-coated dachshund. CVJ , VOL 57, March 2016 7. Eric A. Rowe, Management of Degloving Injuries. NAVC clinician’s brief, August 2007 8. Karen Tobias, Persistent Wound in a Cat. Clinician's Brief, August 2012 BKL/XXX /27Mar20/36pg VET IN/CT3-2 / Disclaimer: The Companion Times is the O? cial newsle er of SAVAVET . Any reproduc on of the same is illegal. SAVAVET is commi ed to provide unbiased informa on to the Indian Veterinary Community. All due credits and cita ons to the authors have been provided. Contributors Business Unit Head Karthik Rajan Dr. Ishan Madelwar Dr. Samiksha Saklani Yatin Hembade Creative Media Manager Product Management Team Product Management Team Please send in your feedback to: [email protected] SAVA HEALTHCARE LIMITED SAVA House, Off New Airport Road, Viman Nagar, Pune - 411 014, INDIA. Tel:+91 20 3051 6100 | Fax:+91 20 3051 6161 | Web: www.savavet.com For detailed information, please reach us on customer care :+91 976 444 3740