Genetics of feline hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is characterized by an abnormal increase in myocardial mass that affects cardiac structure and function. HCM is the most common inherited cardiovascular disease in humans (0.2%) and the most common cardiovascular disease in cats (14.7%). Feline HCM phenotype is very similar to the phenotype found in humans, but the time frame for the development of the disease is significantly shorter. Similar therapeutic agents are used in its treatment and it has the same complications, such as heart failure, thromboembolism and sudden cardiac death. In contrast to humans, in whom thousands of genetic variants have been identified, genetic studies in cats have been limited to fragment analysis of two sarcomeric genes identifying two variants in MYBPC3 and one in MYH7. Two of these variants have also been associated with human disease. The high prevalence of the reported variants in non-affected cats hinders the assumption of their pathogenicity in heterozygotes. An in-depth review of the literature about genetic studies on feline HCM in comparison with the same disease in humans is presented here. The close similarity in the phenotype and genotype between cats and humans makes the cat an excellent model for the pathophysiological study of the disease and future therapeutic agents.

Modulation of IL-33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers.

BACKGROUND: Interleukin (IL)-33 and sST2 are molecules with an opposite pathophysiologic implications in the myocardial response after acute myocardial infarction (AMI). Both may be a target for therapeutic interventions. The kinetics of IL-33 and sST2 expression in infarcted myocardium and their correlation with the ongoing processes of fibrosis, inflammation and apoptosis remains poorly defined. MATERIALS AND METHODS: Fifty Wistar rats underwent left anterior descending coronary artery surgical ligation and were sacrificed at 1, 2, 4, 12 or 24 weeks post-AMI. A sham-operated group was also included. The mRNA cardiac expression levels of IL-33, sST2, fibrosis markers, inflammatory markers and apoptosis markers were assessed by RT-PCR. The protein expression of IL-33 was also measured by Western blotting. RESULTS: The mRNA levels of IL-33 and sST2 were upregulated in the infarcted myocardium during the first week after AMI. However, while IL-33 levels remained elevated during the first 12 weeks post-AMI, sST2 levels showed a marked drop at 4 weeks. IL-33 protein expression showed a similar kinetic than mRNA expression. The expression of sST2 positively correlated with cardiac gene expression of inflammatory and fibrosis markers. However, the IL-33 level did not correlate with these cardiac remodelling markers. No correlation of sST2 with apoptosis markers was observed. CONCLUSION: After AMI, expression of sST2 is rapidly upregulated during the first 4 weeks and, in contrast to IL-33, its levels correlated with the ongoing processes of fibrosis and inflammation. These findings suggest differential regulation of IL33 and sST2. Therapeutic modulation of early sST2 expression may be of greater importance to prevent adverse remodelling after AMI.

Lipid-lowering effect and efficacy after switching to etravirine in HIV-infected patients with intolerance to suppressive HAART.

PURPOSE: Etravirine (ETR) has shown a good lipid profile in previous studies. The aim of this study was to determine the virologic, immunologic, and lipid outcome in HIV-infected patients switching to an ETR-based antiretroviral regimen due to intolerance or toxicity. METHODS: Observational cohort study of 125 HIV-infected patients who switched therapy to an ETR-based regimen. The lipid profile, including total triglycerides (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) was compared after 24 weeks. RESULTS: Patients changed from efavirenz (n = 34; 28%) and ritonavir-boosted protease inhibitors (PI/r; 67 cases: 21 atazanavir, 21 lopinavir, 11 fosamprenavir, 14 darunavir). Hyperlipidemia was the cause in only 22 patients (18%). At 24 weeks, a significant decrease was observed in mean TC level (-8%), LDL-C (-8%), TC:HDL ratio (-6%), and TG level (-20%). For patients receiving previously efavirenz, there was a significant reduction in TC (-23 mg/dL; -13%) and LDL-C (-25 mg/dL; -21%) levels and a trend to a better TG level (-38 mg/dL; -21%;P = .06). In the case of prior PI/r therapy, there was also a significant reduction in TC (-14 mg/dL; -6%) and TG levels (-58 mg/dL; -16%), mostly in prior lopinavir- or fosamprenavir-based therapy (TC -15%; TG -53%). Median CD4+ count increased from 513 to 621 cells/µL (P = .03), and there were only 3 cases of virologic failure (2%). CONCLUSIONS: In patients switching to an ETR-containing regimen, there is a significant improvement of lipids and maintenance of immunologic and virologic response. This lipid-lowering effect was irrespective of the presence of previous hyperlipidemia and for patients receiving different antiretroviral drugs.

The significance of antiretroviral-associated acute kidney injury in a cohort of ambulatory human immunodeficiency virus-infected patients.

BACKGROUND: To determine the incidence and significance of acute kidney injury (AKI) after initiating highly active antiretroviral therapy (HAART). METHODS: A prospective cohort study of 271 consecutively treated HIV-infected patients, initiating first (75) or sequential HAART (196) from January 2008 to June 2011. AKI was diagnosed according to the Risk, Injury, Failure, Loss of kidney function, End-stage renal disease (RIFLE)/Acute Kidney Injury Network (AKIN) criteria, and the risk of progression to chronic kidney disease (CKD) was evaluated. RESULTS: A greater estimated glomerular filtration rate (eGFR) decrease after 1 year was observed for patients initiating a tenofovir disoproxil fumarate (TDF)-based regimen (-6.45 versus +0.98 mL/min/1.73 m(2) when compared with patients without TDF; P < 0.01), both in the case of the first (-8.5 versus -2.27; P = 0.04) or successive regimens (-5.3 versus + 1.18 mL/min/1.73 m(2); P < 0.01). AKI, as defined, was observed in 10% (28 cases, 6.98 episodes/100 patients-year), mostly stage I (27 cases), in a median time of 6 (3-16.5) months. Four cases (14%), having a worse baseline renal function progressed to CKD, whereas four recovered completely. In the multivariate analysis, AKI was associated with the concomitant use of cotrimoxazole prophylaxis and to low CD4+ count. CKD was diagnosed in 2% (six cases) of patients. Therefore, the overall rate of HAART-associated renal disorders was 11% (30 cases, 7.46 episodes/100 patients-year (95% confidence interval, 6.09-8.83). CONCLUSIONS: The initiation of a tenofovir-based regimen is followed by a significant decline in eGFR, although it could be misinterpreted by the concomitant use of cotrimoxazole. A substantial proportion of patients develop AKI, but only a minority progress to CKD. Patients initiating HAART and developing AKI should be carefully monitored for progression of renal disease.

Social isolation in HIV-infected patients according to subjective patient assessment and DEXA-confirmed severity of lipodystrophy.

This study was designed to investigate the persistence of lipodystrophy (LD)-related social distress and isolation in HIV-infected patients in the current era, according to confirmatory dual energy X-ray absorptiometry (DEXA) measurements. Cross-sectional interview data were collected from 168 HIV-positive adult patients taking more than 2 years of antiretroviral therapy (133 cases with LD diagnosed a mean of 7.2 years before; 35 without LD, controls). Mean time of HIV infection was 16.2 years (2.1-27.3), and the mean time of exposure to highly active antiretroviral therapy of 11.7 years (2.1-21.1). The presence and severity of LD, confirmed by DEXA measurements, correlated with social isolation through a validated scale, including avoidance of social relationships, sex, work, or sport activities. In comparison with control patients, social distress was observed for patients having moderate body changes. The significant correlation between LD and social isolation was irrespective of age, CD4+ count, HIV RNA level, AIDS diagnosis, time of HIV infection, anxiety, or depressive symptoms. These results confirm that patient assessment of LD is correlated with whole-body DEXA scan, and they highlight the role of LD as an independent cause of social isolation even after years of the diagnosis.

HIV-1 infection and neurocognitive impairment in the current era.

Brain HIV-1-infection may result in a syndrome of profound cognitive, behavioral and motor impairment known as AIDS dementia complex (ADC) in adults and HIV-related encephalopathy in children. Although the introduction of highly active antiretroviral therapy (HAART) has prolonged and improved the lives of infected individuals, it is clear that HAART does not provide complete protection against neurological damage in HIV/AIDS. HIV-1 associated dementia is a complex phenomenon, which could be the result of several mechanisms caused by those players using different intracellular signaling pathways. Understanding the causes of neurodegeneration during HIV-1 infection and the factors which certain individuals develop disease can provide researches on new therapeutic targets to positively affect disease outcomes. Controlling CNS viral replication with HAART is an essential primary approach, but it should be complemented with adjunctive CNS-directed therapeutics. Understanding the nature of HIV-1 infection within the CNS as well as inflammatory responses will ultimately lead to the elimination of HIV-associated neurocognitive disorders.

Comparative Study of Inhaled Fluticasone Versus Oral Prednisone in 30 Dogs with Cough and Tracheal Collapse.

Coughing is common in dogs with tracheal collapse (TC). The use of inhaled corticosteroids is less widespread than oral ones. This study aims to compare the effects of oral and inhaled corticosteroids in dogs with cough and TC. Thirty dogs were prospectively included and randomized to the prednisone oral group (OG, 14) or fluticasone inhaled group (IG, 16). A clinical score (CS) based on four clinical parameters (respiratory distress, cough episodes, cough frequency, tracheal sensitivity) was monitored at the hospital (enrolment and weeks 2 and 4). Water intake, urination habits, and adherence and tolerance to treatments were monitored weekly. Significant improvements in clinical parameters were identified in both groups throughout the study. Between-group (OG-IG) comparisons revealed no significant differences, indicating equivalent improvement. At the study's endpoint, the IG dogs had a significantly lower CS (5.69 ± 0.79) than OG dogs (6.43 ± 1.02, p < 0.05). Adherence and tolerance were comparable. From weeks 2 to 4, OG dogs were significantly thirstier and urinated more frequently than IG dogs. In conclusion, fluticasone provided good tolerability and efficacy in controlling cough in dogs with TC, and they showed a lower incidence of signs of hypercortisolism compared to prednisone. These data encourage the use of inhaled fluticasone in dogs with cough and TC.

Silencing of microRNA-106b-5p prevents doxorubicin-mediated cardiotoxicity through modulation of the PR55α/YY1/sST2 signaling axis.

Clinical use of doxorubicin (Dox), an anthracycline with potent anti-tumor effects, is limited because of its highly chemotherapy-induced cardiotoxicity (CIC). After myocardial infarction (MI), we have recently identified Yin Yang-1 (YY1) and histone deacetylase 4 (HDAC4) as two factors involved in the overexpression of the isoform soluble suppression of tumorigenicity 2 (sST2) protein, which acts as a decoy receptor blocking the favorable effects of IL-33. Therefore, high levels of sST2 are associated with increased fibrosis, remodeling, and worse cardiovascular outcomes. No data exist on the role of the YY1/HDAC4/sST2 axis in CIC. This study aimed to evaluate the pathophysiological implication of the molecular YY1/HDAC4/sST2 axis in remodeling that is developed in patients treated with Dox as well as to suggest a novel molecular therapy to prevent anthracycline-induced cardiotoxicity. Here, we have characterized a novel nexus between miR106b-5p (miR-106b) levels and the YY1/HDAC4 axis in relation to the cardiac expression of sST2 using two experimental models with Dox-induced cardiotoxicity. The addition of Dox (5 µM) to human induced pluripotent stem cell-derived cardiomyocytes induced cellular apoptotic death via upregulation of miR-106b-5p (miR-106b), which was confirmed by specific mimic sequences. A functional blockage of miR-106b using the locked nucleic acid antagomir inhibited Dox-induced cardiotoxicity.

Age and Sex Determine Electrocardiogram Parameters in the Octodon degus.

Cardiovascular diseases represent the leading cause of mortality and morbidity worldwide, and age is an important risk factor. Preclinical models provide supportive evidence toward age-related cardiac changes, as well as allow for the study of pathological aspects of the disease. In the present work, we evaluated the electrocardiogram (ECG) recording in the O. degus during the aging process in both females and males. Taking into account the age and sex, our study provides the normal ranges for the heart rate, duration and voltage of the ECG waves and intervals, as well as electrical axis deviation. We found that the QRS complex duration and QTc significantly increased with age, whereas the heart rate significantly decreased. On the other hand, the P wave, PR and QTc segments durations, S wave voltage and electrical axis were found to be significantly different between males and females. The heart rhythm was also altered in aged animals, resulting in an increased incidence of arrhythmias, especially in males. Based on these results, we suggest that this rodent model could be useful for cardiovascular research, including impacts of aging and biological sex.

Reverse Sneezing in Dogs: Observational Study in 30 Cases.

Reverse sneezing (RS) is a frequent reason for veterinary consultation, but there is scarce clinical information. The aim of this study was to describe clinical characteristics in a cohort of 30 dogs with RS. Signalment, clinical features, results of diagnostic tests, final diagnosis, and evolution were retrospectively evaluated. Sex and neuter status were equally distributed into diagnosis categories. A significantly higher representation of toys (<5 kg, 50%) and small-sized dogs (5−15 kg, 27%), in comparison to medium (15−30 kg, 17%) and large-sized dogs (>30 kg, 7%), was found. RS was the main owner concern in many of the cases (67%). Many cases presented chronic RS (60%, > 3 months), with more than one episode a week (60%). Most cases had an additional clinical respiratory sign (63%) and an unremarkable physical examination (63%). Inflammatory airway disorders were present in 57% of the cases, followed by anatomical−functional disorders (27%), and nasal/nasopharyngeal foreign bodies (10%). Two dogs (7%) remained as open diagnoses. Episodes of RS were persistent despite the treatment in 61% of the dogs with follow-up. Although some dogs manifest infrequent episodes of RS, being otherwise normal, RS should be considered a marker of potential irritation of the nasopharyngeal mucosa and should always be sufficiently investigated.

Clinical and Electrocardiographic Findings for Predicting the Severity of Pulmonary Valve Stenosis in Dogs.

Pulmonary valve stenosis (PS) in dogs is usually suspected due to the presence of a heart murmur and clinical signs. Echocardiography is needed to confirm the diagnosis and define the severity of PS. This retrospective study evaluated the utility of clinical and electrocardiographic (ECG) findings in the prediction of PS severity. Data regarding heart murmur and ECG analysis were gathered. Ninety-seven dogs with PS were included. A murmur grade ≥IV/VI was predictive of severe PS (area under curve (AUC) = 0.71; sensitivity (Se) = 95%; specificity (Sp) = 33%; p = 0.003). In lead II, P wave amplitude >0.35 mV (AUC = 0.67; Se = 31%; Sp = 100%; p = 0.038), Q wave < 0.15 mV (AUC = 0.70; Se = 70%; Sp = 59%; p = 0.0015), R wave < 0.87 mV (AUC = 0.66; Se = 67%; Sp = 69%; p = 0.006), and S wave > 0.37 mV (AUC = 0.80; Se = 72%; Sp = 85%; p < 0.0001) were predictive of severe PS. The extent of right deviation of the mean electrical axis of the QRS complex was correlated with the pulmonary pressure gradient (r = 0.648; p < 0.0001). In conclusion, a systolic murmur with intensity ≥IV/VI, a P wave amplitude >0.35 mV, low amplitude of Q and R waves, deep S waves in lead II, and right axis deviation of the QRS complex in a young dog are predictive of severe PS.

Safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with advanced liver disease.

PURPOSE: There are few data about the safety and pharmacokinetics of lopinavir in HIV/HCV coinfected patients with very advanced liver disease. METHOD: Prospective study of 60 HIV/HCV coinfected patients who underwent a liver biopsy and received a lopinavir-based regimen. The rate of hepatotoxiciy and plasma trough levels were determined in absence/presence of cirrhosis (25 cases), especially in 11 patients with Child-Pugh stage B-C. RESULTS: Overall, geometric mean level of lopi-navir was 7,109 ng/mL (interquartile range [IQR], 5,163-9,029), without differences according to cirrhosis (7,662; IQR, 5,165-10,442) or not (6,708; IQR, 5,524-8,526; P = .6). In 11 patients with Child-Pugh stage B-C, trough level was 9,640 ng/mL (IQR, 1,620-11,622 ng/mL), but there was a 99% interpatient variability (72 to 13,331 ng/mL). During a follow-up of 195.2 patient-years, there were 7 cases of hepatotox-icity, with an incidence of 3.39 episodes/100 patient-years (2.2 to 7.9). This incidence was higher in patients with Child-Pugh stage B-C (5.43 episodes/100 patient-years). There were no differences in lopinavir trough levels between patients with or without liver toxicity (7,100 vs 7,119 ng/mL; P = .9). CONCLUSION: The risk of lopinavir-associated hepatotoxicity in patients with very advanced liver disease is low. However, lopinavir plasma trough levels are increased, and there is a high interpatient variability.

The miRNA199a/SIRT1/P300/Yy1/sST2 signaling axis regulates adverse cardiac remodeling following MI.

Left ventricular remodeling following myocardial infarction (MI) is related to adverse outcome. It has been shown that an up-regulation of plasma soluble ST2 (sST2) levels are associated with lower pre-discharge left ventricular (LV) ejection fraction, adverse cardiovascular outcomes and mortality outcome after MI. The mechanisms involved in its modulation are unknown and there is not specific treatment capable of lowering plasma sST2 levels in acute-stage HF. We recently identified Yin-yang 1 (Yy1) as a transcription factor related to circulating soluble ST2 isoform (sST2) expression in infarcted myocardium. However, the underlying mechanisms involved in this process have not been thoroughly elucidated. This study aimed to evaluate the pathophysiological implication of miR-199a-5p in cardiac remodeling and the expression of the soluble ST2 isoform. Myocardial infarction (MI) was induced by permanent ligation of the left anterior coronary artery in C57BL6/J mice that randomly received antimiR199a therapy, antimiR-Ctrl or saline. A model of biomechanical stretching was also used to characterize the underlying mechanisms involved in the activation of Yy1/sST2 axis. Our results show that the significant upregulation of miR-199a-5p after myocardial infarction increases pathological cardiac hypertrophy by upregulating circulating soluble sST2 levels. AntimiR199a therapy up-regulates Sirt1 and inactivates the co-activator P300 protein, thus leading to Yy1 inhibition which decreases both expression and release of circulating sST2 by cardiomyocytes after myocardial infarction. Pharmacological inhibition of miR-199a rescues cardiac hypertrophy and heart failure in mice, offering a potential therapeutic approach for cardiac failure.

Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.

Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have shown to prevent heart failure progression, although the mechanisms remain poorly understood. Here we evaluated the effect of empagliflozin (EMPA, SGLT2i) in cardiac remodeling after myocardial infarction, the interplay with diabetes status and the role of cardiac GTP enzyme cyclohydrolase 1 (cGCH1). A rat model of diabetes (50 mg/kg streptozotocin, i.p.) was subjected to myocardial infarction and left ventricular systolic dysfunction, by ligation of the left anterior descending coronary artery. EMPA therapy significantly improved cardiac remodeling parameters and ameliorated processes of fibrosis and hypertrophy, in both non-diabetic and diabetic rats. This cardioprotective effect related with a significant increase in myocardial expression levels of cGCH1, which led to activation of nNOS and eNOS, and inhibition of iNOS, and subsequently resulted in increasing of NO levels and decreasing O2.- and nitrotyrosine levels. These effects were replicated in a cardiomyocyte biomechanical stretching diabetic model, where silencing cGCH1 blocked the preventive effect of EMPA. The beneficial effects were observed irrespective of diabetes status, although the magnitude was greater in presence of diabetes. Empagliflozin improves myocardial remodeling after myocardial infarction through overexpression of cGCH1, and irrespective of diabetes status.

Author Correction: Empagliflozin improves post-infarction cardiac remodeling through GTP enzyme cyclohydrolase 1 and irrespective of diabetes status.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Temporal changes in clinical and radiographic variables in dogs with preclinical myxomatous mitral valve disease: The EPIC study.

BACKGROUND: The Evaluation of pimobendan in dogs with cardiomegaly caused by preclinical myxomatous mitral valve disease (EPIC) study monitored dogs with myxomatous mitral valve disease (MMVD) as they developed congestive heart failure (CHF). OBJECTIVES: To describe the changes in clinical and radiographic variables occurring as dogs with MMVD and cardiomegaly develop CHF, compared to similar dogs that do not develop CHF. ANIMALS: One hundred and thirty-five, and 73 dogs that did or did not develop CHF, respectively. MATERIALS AND METHODS: The following variables were evaluated in 2 groups of dogs (dogs that did or did not develop CHF): Heart rate (HR), clinic respiratory rate (RR), home-measured resting respiratory rate (RRR), rectal temperature (RT), body weight (BW), and vertebral heart sum (VHS). Absolute value and rate of change of each variable were calculated for each day a dog was in study. Daily means were calculated and plotted against time. The onset of CHF or last visit before leaving the study were set as reference time points. RESULTS: The most extreme values and rate of change occurred in variables immediately before onset of CHF. Vertebral heart sum increased earliest. Heart rate, RR, and RRR also increased. Rectal temperature and BW decreased. Increases in RR and RRR were most extreme and occurred immediately before CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: Dogs with MMVD and cardiomegaly experience increases in HR, RR, RRR, and VHS, and decreases in BW and RT as they develop CHF. The variables with highest absolute change and rate of change were RR and RRR. These findings reinforce the value of RR and RRR as indicators of impending or incipient CHF.

Transthoracic Echocardiographic Examination in the Rabbit Model.

Large animal models such as the rabbit are valuable for translational preclinical research. Rabbits have a similar cardiac electrophysiology compared to that of humans and that of other large animal models such as dogs and pigs. However, the rabbit model has the additional advantage of lower maintenance costs compared to other large animal models. The longitudinal evaluation of cardiac function using echocardiography, when appropriately implemented, is a useful methodology for preclinical assessment of novel therapies for heart failure with reduced ejection fraction (e.g. cardiac regeneration). The correct use of this non-invasive tool requires the implementation of a standardized examination protocol following international guidelines. Here we describe, step by step, a detailed protocol supervised by veterinary cardiologists for performing echocardiography in the rabbit model, and demonstrate how to correctly obtain the different echocardiographic views and imaging planes, as well as the different imaging modes available in a clinical echocardiography system routinely used in human and veterinary patients.

Long-term incidence and risk of noncardiovascular and all-cause mortality in apparently healthy cats and cats with preclinical hypertrophic cardiomyopathy.

BACKGROUND: Epidemiologic knowledge regarding noncardiovascular and all-cause mortality in apparently healthy cats (AH) and cats with preclinical hypertrophic cardiomyopathy (pHCM) is limited, hindering development of evidence-based healthcare guidelines. OBJECTIVES: To characterize/compare incidence rates, risk, and survival associated with noncardiovascular and all-cause mortality in AH and pHCM cats. ANIMALS: A total of 1730 client-owned cats (722 AH, 1008 pHCM) from 21 countries. METHODS: Retrospective, multicenter, longitudinal, cohort study. Long-term health data were extracted by medical record review and owner/referring veterinarian interviews. RESULTS: Noncardiovascular death occurred in 534 (30.9%) of 1730 cats observed up to 15.2 years. Proportion of noncardiovascular death did not differ significantly between cats that at study enrollment were AH or had pHCM (P = .48). Cancer, chronic kidney disease, and conditions characterized by chronic weight-loss-vomiting-diarrhea-anorexia were the most frequently recorded noncardiovascular causes of death. Incidence rates/risk of noncardiac death increased with age in AH and pHCM. All-cause death proportions were greater in pHCM than AH (65% versus 40%, respectively; P < .001) because of higher cardiovascular mortality in pHCM cats. Comparing AH with pHCM, median survival (study entry to noncardiovascular death) did not differ (AH, 9.8 years; pHCM, 8.6 years; P = .10), but all-cause survival was significantly shorter in pHCM (P = .0001). CONCLUSIONS AND CLINICAL IMPORTANCE: All-cause mortality was significantly greater in pHCM cats due to disease burden contributed by increased cardiovascular death superimposed upon noncardiovascular death.

Broncholithiasis in a cat: clinical findings, long-term evolution and histopathological features.

A 14-year-old neutered male Persian cat was evaluated because of an acute exacerbation of a chronic cough of 2-3 years of duration. Physical examination was normal except for the auscultation of accentuated breath sounds and wheezes cranially on both sides of the chest. Complete blood count, biochemical parameters and urinalysis were normal. Thoracic radiographs showed a generalised nodular pattern with multiple mineral opacities. Oral prednisone and doxycycline were prescribed. Two weeks later, the frequency of the cough was significantly reduced. Terbutaline was recommended for relief of acute exacerbations. Three years later the cat was evaluated again due to a non-related disease that led to the euthanasia of the cat. Concerning its respiratory disease, the cat had experienced nearly asymptomatic periods of 3-6 weeks of duration punctuated by acute exacerbation periods of 7-10 days, during which terbutaline was useful to relieve the cough. Thoracic radiographs showed a mild increase in the size and extent of the pulmonary mineralisation. Histopathologically, mild bronchitis and bronchiectasis were evident, accompanied by calcified bronchial plugs and marked hyperplasia and hypertrophy of the seromucinous glands. Based on clinical and pathoanatomical findings, a final diagnosis of miliary broncholithiasis and bronchiectasis was made. Broncholithiasis should be considered in differential diagnosis of pulmonary mineralisation in cats. When no concomitant diseases are present, this rare disease appears to have a slowly progressive evolution that does not appear to carry a bad prognosis and may be satisfactorily managed with combinations of bronchodilators and corticosteroids.

Echocardiographic evaluation of the right ventricular dimension and systolic function in dogs with pulmonary hypertension.

BACKGROUND: Right ventricular (RV) enlargement and dysfunction are associated with prognosis in humans with pulmonary hypertension (PH). HYPOTHESIS/OBJECTIVES: To assess RV size and systolic function in dogs with PH and to determine if they are associated with disease severity and right-sided congestive heart failure (R-CHF). ANIMALS: 89 dogs with PH and 74 healthy dogs. METHODS: Prospective observational study. PH was classified according to the tricuspid regurgitation pressure gradient. RV end-diastolic area (RVEDA) index was calculated as RVEDA divided by body surface area. RV systolic function was assessed with the tricuspid annular plane systolic excursion (TAPSE) and the RV fractional area change (FAC) normalized for body weight (TAPSEn and FACn, respectively). RESULTS: RVEDA index was higher in dogs with moderate PH (10.8 cm2 /m2 ; range, 6.2-14.4 cm2 /m2 ) and severe PH (12.4 cm2 /m2 ; range, 7.7-21.4 cm2 /m2 ) than in those with mild PH (8.4 cm2 /m2 ; range, 4.8-11.6 cm2 /m2 ) and control dogs (8.5 cm2 /m2 ; range, 2.8-11.6 cm2 /m2 ; P < .001). RVEDA index was significantly higher in dogs with R-CHF (13.7 cm2 /m2 ; range, 11.0-21.4 cm2 /m2 ) than in dogs without R-CHF (9.4 cm2 /m2 ; range, 4.8-17.1 cm2 /m2 ; P < .001). The severity of tricuspid regurgitation (TR) was the only independent predictor of the RVEDA index (P < .001). TAPSEn and FACn were not significantly different among varying degrees of PH severity and between dogs with and without R-CHF. CONCLUSIONS AND CLINICAL IMPORTANCE: The RVEDA index can be used to evaluate RV size in dogs. It can provide additional information in dogs with PH and predict R-CHF. Severity of TR is the main determinant of RV enlargement in dogs with PH.