Onset Of Congestive Heart Failure Research Articles

Comparative Analysis of Modified BT Shunt and Central Shunt in Pediatric Patients.

Cyanotic congenital heart diseases constitute 40-45% of all congenital heart diseases. In patients who are not suitable for primary repair, modified BT (MBT) shunt and central shunt (CS) procedures are still frequently used. This study included 62 pediatric patients who underwent MBT shunt or CS via median sternotomy. Patients' demographic, echocardiographic, operative, and postoperative data were collected retrospectively. The patients were classified as single ventricle and bi-ventricle according to their cardiac anatomy, and the presence of prematurity and heterotaxy was noted. Procedure details of the patients who underwent endovascular intervention prior to the surgery were investigated, and operation data were accessed from the surgery notes. Data regarding postoperative follow-ups were obtained and comparatively analyzed. Of the total 62 patients, 32 (51.6%) were newborns and 16 (25.8%) had a body weight < 3 kg. MBT shunt was applied to 48 patients (77.4%), while CS was applied to 14 patients (22.6%). There was no significant difference between the two surgical procedures in terms of requirement for urgent shunt or cardiopulmonary bypass, additional simultaneous surgical intervention, need for high postoperative inotropes, and in-hospital mortality (P>0.05). The rate of congestive heart failure in patients with in-hospital mortality was determined as 66.7% and it was significantly higher than in patients without heart failure (P<0.001). MBT shunt and CS are still frequently used in cyanotic patients. The use of small-diameter shunts, particularly when centrally located, can prevent the onset of congestive heart failure and lower mortality.

Efficacy of a mitral regurgitation severity index to predict long-term outcome in dogs with myxomatous mitral valve disease.

Predicting progression of myxomatous mitral valve disease (MMVD) in dogs can be challenging. The mitral regurgitation severity index (MRSI) will predict time to congestive heart failure (CHF) and all-cause death in dogs with MMVD. Eight hundred sixty-nine client-owned dogs. Retrospective study pooling data from 4 previous samples including dogs with MMVD stage B2 or C. MRSI was calculated as: (heart rate [HR]/120) × left atrium-to-aorta ratio (LA:Ao) × (age in years/10) × 100. Alternative MRSI formulas substituting radiographic measures of left atrial size were also calculated. Cox proportional hazard modeling and time-dependent receiver-operator characteristic curves quantified prognostic performance. For Stage B2 pooled samples, MRSI > 156 was predictive of time to CHF (median 407 vs 1404 days; area under the curve [AUC] 0.68; hazard ratio 3.02 [95% CI 1.9-4.9]; P < .001). MRSI > 173 was predictive of all-cause death (median survival 868 vs 1843 days; AUC 0.64; hazard ratio 4.26 [95% CI 2.4-7.5]; P < .001). MRSI showed superior predictive value compared to the individual variables of HR, LA:Ao, and age. Variations of the MRSI equation substituting radiographic vertebral left atrial size for LA:Ao were also significantly predictive of outcome in stage B2. MRSI was not consistently predictive of outcome in Stage C. MRSI was predictive of outcome (onset of CHF and all-cause death) in MMVD Stage B2, demonstrating utility as a useful prognostic tool. Echocardiographic LA:Ao can be effectively replaced by radiographically determined LA size in the MRSI formula.

Negative correlation between organ heteroplasmy, particularly hepatic heteroplasmy, and age at death revealed by post-mortem studies of m.3243A > G cases

Mitochondrial DNA m.3243A > G mutation causes mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) and its associated multi-organ disorders, including diabetes. To clarify associations between m.3243A > G organ heteroplasmy and clinical phenotypes, including the age at death, we combined genetic and pathological examinations from seven unreported and 36 literature cases of autopsied subjects. Clinical characteristics of subjects were as follows: male, 13; female, 28; unknown, 2; the age at death, 36.9 ± 20.2 [4–82] years; BMI, 16.0 ± 2.9 [13.0–22.3]; diabetes, N = 21 (49%), diabetes onset age 38.6 ± 14.2 years; deafness, N = 27 (63%); stroke-like episodes (StLEp), N = 25 (58%); congestive heart failure (CHF), N = 15 (35%); CHF onset age, 51.3 ± 14.5 years. Causes of death (N = 32) were as follows: cardiac, N = 13 (41%); infection, N = 8 (25%); StLEp, N = 4 (13%); gastrointestinal, N = 4 (13%); renal, N = 2 (6%); hepatic, N = 1 (2%). High and low heteroplasmies were confirmed in non-regenerative and regenerative organs, respectively. Heteroplasmy of the liver, spleen, leukocytes, and kidney for all subjects was significantly associated with the age at death. Furthermore, the age at death was related to juvenile-onset (any m.3243A > G-related symptoms appeared before 20) and stroke-like episodes. Multiple linear regression analysis with the age at death as an objective variable showed the significant contribution of liver heteroplasty and juvenile-onset to the age at death. m.3243A > G organ heteroplasmy levels, particularly hepatic heteroplasmy, are significantly associated with the age at death in deceased cases.

Pimobendan prevents cardiac dysfunction, mitigates cardiac mitochondrial dysfunction, and preserves myocyte ultrastructure in a rat model of mitral regurgitation

BackgroundPimobendan has been proven to delay the onset of congestive heart failure (CHF) in dogs with mitral regurgitation (MR); however, molecular underlying mechanisms have not been fully elucidated. This study aimed to investigate (1) the effects of pimobendan on cardiac function, cardiac mitochondrial quality and morphology, and cardiac ultrastructure in a rat model of chronic MR and (2) the direct effect of pimobendan on intracellular reactive oxygen species (ROS) production in cardiac cells. MR was surgically induced in 20 Sprague-Dawley rats, and sham procedures were performed on 10 rats. Eight weeks post-surgery, the MR rats were randomly divided into two groups: the MR group and the MR + pimobendan group. Pimobendan (0.15 mg/kg) was administered twice a day via oral gavage for 4 weeks, whereas the sham and MR groups received equivalent volumes of drinking water. Echocardiography was performed at baseline (8 weeks post-surgery) and at the end of the study (4 weeks after treatment). At the end of the study protocol, all rats were euthanized, and their hearts were immediately collected, weighed, and used for transmission electron microscopy and mitochondrial quality assessments. To evaluate the role of pimobendan on intracellular ROS production, preventive or scavenging properties were tested with H2O2-induced ROS generation in rat cardiac myoblasts (H9c2).ResultsPimobendan preserved cardiac functions and structure in MR rats. In addition, pimobendan significantly improved mitochondrial quality by attenuating ROS production and depolarization (P < 0.05). The cardiac ultrastructure and mitochondrial morphology were significantly preserved in the MR + pimobendan group. In addition, pimobendan appeared to play as a ROS scavenger, but not as a ROS preventer, in H2O2-induced ROS production in H9c2 cells.ConclusionsPimobendan demonstrated cardioprotective effects on cardiac function and ultrastructure by preserving mitochondrial quality and acted as an ROS scavenger in a rat model of MR.

Cardiovascular Complications of CD 19 Chimeric Antigen Receptor-T Cell Therapy: A Systematic Review

Corresponding Author: Muhammad Umair Mushtaq, MD Assistant Professor of Medicine Division of Hematologic Malignancies and Cellular Therapeutics University of Kansas Medical Center 2330 Shawnee Mission Parkway, Suite 210, MS 5003, Westwood, KS 66205 Email: mmushtaq@kumc.edu Background: Anti CD19 chimeric antigen receptor (CAR) T cell therapy is being utilized for the treatment of patients with refractory and relapsing hematologic malignancies with propitious results. It has resulted in a significant increase in overall survival and reduced relapse rate. However, a multitude of cardiac complications has been observed with this therapy. This systematic review aims at cardiovascular complications of CD 19 CAR-T cell therapy. Methodology: Following the preferred reporting items for systemic reviews and Meta-analysis (PRISMA) guidelines, a comprehensive literature search was performed on three databases (PubMed, Cochrane Register of Controlled Trials, and Clinicaltrials.gov) using MeSH terms and keywords for "cardiovascular complications" AND "CAR-T Cell therapy" from the date of inception to May 16, 2022. Our search produced 354 results, and duplicates were removed. After excluding irrelevant and review articles during primary and secondary screening, ten studies were included which mentioned cardiovascular side effects of CAR-T cell therapy. Results: A total of 3004 patients from ten studies were included for this systematic review. The median age of patients was 57 (2-72) years, and 62% were male. (Table 1) All included studies used CD19 CAR-T cell therapy except Qi et al. which used CD20 and CD22 in addition to CD19. Eight studies were retrospective, and two were clinical trials. As per the available data, Troponemia was the most commonly reported cardiac side effect of CART therapy with an incidence of 18.3% (n=54), followed by arrhythmias at 4.9% (n=138), new onset of congestive heart failure 4.8% (n=144), and acute coronary syndrome (ACS) 4.1% (n=11). CHF decompensation, cardiogenic shock, venous thromboembolism, and myocarditis was observed in 3.2% (n=20), 3.1% (n=76), 1.5%(n=35), 0.8% (n=4) of the patients, respectively. Cardiac arrest due to CAR-T cell therapy occurred in 1.5% (n=8) of patients, while death due to cardiac causes occurred in 1.9% (n=48) of the patients. Conclusion: The overall rate of cardiotoxicity associated with CAR-T cell therapy is low and further studies are need of the hour to consolidate these findings. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Change of Vertebral Left Atrial Size in Dogs With Preclinical Myxomatous Mitral Valve Disease Prior to the Onset of Congestive Heart Failure

Introduction/objectivesIt has been proposed that vertebral left atrial size (VLAS) on thoracic radiographs can be used to assess the left atrial enlargement in dogs with myxomatous mitral valve disease (MMVD). However, it remains unclear whether VLAS can be used to distinguish dogs between pre-clinical MMVD that are at a greater risk of developing congestive heart failure (CHF) from those at a lower risk. We investigated this possibility. Animals, materials and methodsForty-one dogs with MMVD were retrospectively classified into one of two groups, a group that developed CHF (group CHF, n = 17) or remained CHF-free (group no-CHF, n = 24). The value of vertebral heart scale (VHS) and VLAS at three time-points, change in VHS and VLAS at a specific time interval (ΔVHS, ΔVLAS) and rate of change in the values per month (ΔVHS/month, ΔVLAS/month) were compared. ResultsAt the first visit, there were no significant differences in VLAS between the groups. At the median of 105 (interquartile ranges 83–155) days prior to the onset of CHF (group CHF) or the last visit (group no-CHF), VLAS was significantly higher in group CHF (mean, 2.9; standard deviation ± 0.4) than in group no-CHF (2.6 ± 0.3) (p = 0.028). ΔVLAS/month (area under the curve, 0.91; p<0.001) showed high diagnostic accuracy in distinguishing which dogs would develop CHF within 180 days and which would not. ConclusionsVLAS and ΔVLAS/month in dogs with pre-clinical MMVD may be useful to identify dogs at risk of developing CHF within the next 180 days.

Severe cardiomyopathy associated with the VCP p.R155C and c.177_187del MYBPC3 gene variants

Inclusion Body Myopathy, Paget's Disease of Bone, with Frontotemporal Dementia is a progressive autosomal dominant disease that affects the ubiquitin-proteasome complex, that is caused by variants in the Valosin Containing Protein (VCP) gene. We report the first case of concurrent pathogenic variants in both MYBPC3 and VCP that led to earlier onset of congestive heart failure with features of dilated cardiomyopathy. Cardiomyopathy has previously been associated with VCP inclusion body myopathy mostly at an advanced stage of the disease. Due to acute onset of cardiomyopathy in a previous asymptomatic individual, a cardiomyopathy gene panel was obtained which revealed an additional c.177_187del variant of the MYBPC3 gene. We report a first case of concurrent pathogenic variants in both c.177_187del gene of MYBPC3 and p.R155C VCP that led to earlier onset and a more severe form of the cardiomyopathy.

Detection of Congestive Heart Failure and Myocardial Dysfunction in Cats With Cardiomyopathy by Using Two-Dimensional Speckle-Tracking Echocardiography.

Congestive heart failure (CHF) is a life-threatening condition in cats with cardiomyopathy. We hypothesized that myocardial dysfunction may induce progression to CHF pathophysiology in cats with cardiomyopathy. However, no previous studies have evaluated the involvement of myocardial dysfunction in cats with CHF. In this study, we aimed to evaluate the relationship between CHF and myocardial function assessed using two-dimensional speckle-tracking echocardiography (2D-STE). Sixteen client-owned healthy cats and 32 cats with cardiomyopathy were enrolled in this study. Cats were classified into three groups: healthy cats, cardiomyopathy without CHF (CM group), and cardiomyopathy with CHF (CHF group). Left ventricular (LV) longitudinal and circumferential strains (SL and SC, respectively), and right ventricular (RV) SL were measured using 2D-STE. Logistic regression analysis was performed to assess the relationship between CHF and echocardiographic variables, including 2D-STE. Results comparing the healthy cats and CM vs. CHF groups showed that increased left atrial to aortic diameter ratio and decreased LV apical SC were significantly associated with the existence of CHF (odds ratio [95% confidence interval]: 1.40 [1.16–1.78] and 1.59 [1.06–2.36], respectively). Results comparing the CM vs. CHF group showed that increased end-diastolic RV internal dimension and decreased RV SL were significantly associated with the existence of CHF (odds ratio: 1.07 [1.00–1.13] and 1.34 [1.07–1.68], respectively). Left atrial enlargement and depressed LV apical myocardial function may be useful tools for predicting the progression to CHF in cats. Furthermore, RV enlargement and dysfunction may lead to the onset of CHF in asymptomatic cats with cardiomyopathy.

Development of a Risk Score for Cardiovascular Events in Anthracycline Treated DLBCL Patients

Introduction:There is increased risk of congestive heart failure (CHF) following anthracycline-based chemotherapy in patients with Diffuse Large B-cell lymphoma (DLBCL). Other than increased cumulative anthracycline dose, little is known about risk factors for developing CHF and other cardiovascular events (CVE).Methods:We conducted a retrospective analysis of 539 DLBCL patients diagnosed at University Hospitals Seidman Cancer Center between 2002 - 2016. Baseline patient and disease characteristics, patterns of treatment and outcomes after therapy, including response, survival, relapse, CVE, and causes of death were collected.Time-to-CVE was measured from the date of DLBCL diagnosis to the date of CVE diagnosis and censored at the date of last follow-up for those without CVE, considering death as competing risk. The cumulative incidence of CVE was estimated taking death as competing risk into account. Univariate and multivariable analysis on time-to-CVE was done using Gray's method. Multicollinearity was tested and some of the highly correlated covariables were excluded in the final analysis. CVE risk scores were computed for each patient as a linear combination of the factors included in the multivariable model and their respective coefficients. The optimal cutoff point was identified by searching the spectrum of the risk scores to have the best discrimination of time-to-CVE among patients at low/high risks. All tests were two-sided and p-value ≤ 0.05 were considered statistically significant.Results:We identified 463 patients who received anthracycline to be included in the statistical analysis. Baseline clinical and disease characteristics including comorbidities, clinical risk factors are outlined in Table 1.After a median follow up of 71.1 (range: 0.3 - 216.1) months, 5-year PFS was 59% with median PFS of 82.7 (95% Cl: 71.1 - 115.7) months and 5-year OS was 71% with median OS of 152.6 (95% CI: 127.5 - 162) months.CVE were identified in 92 patients (19.9%), with 128 events identified. The most common CVE was new onset of CHF in 10.4% of patients, followed by atrial fibrillation (4.9%) and asymptomatic heart failure ( 3%) (Table 2).The 3, 6 and 9-year cumulative incidence of CVE for early stage was 13.1%, 15.2% and 18.5%, respectively and 22.2%, 31.4% and 36.5% for advanced stage, respectively (p-value = 0.026). Similarly, the cumulative incidence of CVE was increased in patients with diabetes, with a 3-year cumulative incidence of CVE of 9.4% vs. 17.5% in patients with and without diabetes, respectively.Proportional hazards regression for time-to-CVE identified age >65 years, CD10 expression by IHC, diabetes, and hypertension as significant predictors of time-to-CVE on univariate analysis. On multivariable regression analysis with advanced age at diagnosis, stage, baseline lymphocyte count, and diabetes; stage was still significant in predicting time-to- CVE controlling the effects of advanced age and diabetes, which were also marginally significant.A predictive formula was created to help identify patients at highest risk for cumulative incidence of CVE. Using advanced age (over 65 years of age), baseline lymphocyte count above 800/µL, advanced stage at diagnosis and history of diabetes patients could be stratified into groups with low, intermediate and high risk for CVE (Table 4 and Figure 1).Risk score = Age >65 (3 points) + Lymphocyte count > 800/µL (-1 point) + Stage III/IV(8 points) + Diabetes (3 points) (Table 3)One-year cumulative incidence of CVE was 5.3% for low-risk patients, 7.9% for intermediate risk patients and 13.4% for high risk patients (Figure 1).Conclusions:Our analysis indicates a high risk of CVE in anthracycline treated DLBCL patients, with 19.9% of patients having a CVE in our cohort. The proposed CVE predictive score uses clinical and laboratory parameters routinely collected on all new DLBCL patients and can be easily assessed in the clinical setting. Patients in the high-risk group have a cumulative incidence of CVE of 13.4% at 1 year and would likely benefit from surveillance and interventions. Use of a clinical risk score can aid in the identification of patients at highest CVE risk to conduct studies of surveillance and prevention of this common complication. [Display omitted] DisclosuresBoughan: Beigene: Speakers Bureau. Caimi: Seattle Genetics: Consultancy; Verastem: Consultancy; Amgen Therapeutics.: Consultancy; Kite Pharmaceuticals: Consultancy; TG Therapeutics: Honoraria; ADC Theraputics: Consultancy, Research Funding; Genentech: Research Funding; XaTek: Patents & Royalties: Royalties from patents (wife).

The Role of Matrix Metalloproteinases in the Progression and Vulnerabilization of Coronary Atherosclerotic Plaques

Abstract Extracellular matrix (ECM) plays an important role in the development and progression of atherosclerotic lesions. Changes in the ECM are involved in the pathophysiology of many cardiovascular diseases, including atherosclerosis. Matrix metalloproteinases (MMPs) are a family of zinc-dependent proteases, also known as matrixins, with proteolytic activity in the ECM, being responsible for the process of tissue remodeling in various systemic pathologies, including cardiac and vascular diseases. MMPs play an important role in maintaining normal vascular structure, but also in secondary cardiovascular remodeling, in the formation of atherosclerotic plaques and in their vulnerabilization process. In addition to the assigned effect of MMPs in vulnerable plaques, they have a well-defined role in post-infarction ventricular remodeling and in various types of cardiomyopathies, followed by onset of congestive heart failure, with repeated hospitalizations and death. The aim of this manuscript was to provide a summary on the role of serum matrix metalloproteinases in the process of initiation, progression and complication of atherosclerotic lesions, from a molecular level to clinical applicability and risk prediction in patients with vulnerable coronary plaques.

Preliminary Outcome of a Novel Edge-to-Edge Closure Device to Manage Mitral Regurgitation in Dogs.

Background: Veterinary management of mitral valve regurgitation due to mxyomatous valve disease in dogs is limited to medical treatments, which only postpones the onset of congestive heart failure or alleviates clinical symptoms. Most surgical procedures to manage this condition in humans require cardiopulmonary bypass and have a high risk of complications.Animals: Eight dogs with naturally occurring mitral valve regurgitation.Methods: Prospective observational study. All dogs were treated with a novel edge-to-edge transcatheter device named ValveClamp. The total surgical procedural time and total catheterization time were recorded. Echocardiographic variables measured pre- and post-procedure were compared using Wilcoxin-signed rank test with a P < 0.05 considered significant. Data were expressed as median and interquartile range and absolute numbers and percentages.Results: The procedural success rate was 100% and all the dogs survived without complications. The median (interquartile range) total surgical procedural time was 86.5 (76–96.2) minutes and catheterization time was 23.5 (22–33.8) minutes. Echocardiography revealed a significant reduction in mitral regurgitation severity in all dogs following the procedure based on both a reduced mitral regurgitant maximum jet area (P = 0.012) and a reduced mitral regurgitant maximum jet area to left atrial area (P = 0.018).Conclusion: The ValveClamp device is effective at reducing the severity of mitral regurgitation in dogs with naturally occurring myxomatous valve disease.

Cardiac magnetic resonance imaging features prognostic information in patients with suspected myocardial infarction with non-obstructed coronary arteries

BackgroundTo assess the prognostic implications of cardiac magnetic resonance imaging (CMR) in patients with clinical suspicion of myocardial infarction with non-obstructed coronary arteries (MINOCA). MethodsA total of 145 patients (58 ± 15 years, 97 men) were retrospectively enrolled in this single-center, longitudinal observational study. All patients underwent CMR including cine, edema-sensitive, and late gadolinium enhancement acquisitions, within a median of 3 days after cardiac catheterization. Follow-up was performed by medical records chart review and phone interviews; the median follow-up time was 4.2 years. The primary endpoint was defined as a combination of death, stroke, new onset of congestive heart failure, recurrent hospitalization, or the need for an invasive cardiac procedure. ResultsIn 143 (98.6%) cases, CMR revealed the following cardiac pathologies: myocarditis (n = 48, 33.1%), structural cardiomyopathies (n = 40, 27.6%), “true” myocardial infarction (n = 22, 15.1%), hypertensive heart disease (n = 19, 13.1%), and Tako-Tsubo cardiomyopathy (n = 14, 9.7%). Only two patients (1.4%) had a normal CMR examination. There were significant prognostic differences between different etiologies, e.g. myocarditis and Tako-Tsubo cardiomyopathy had a more favorable prognosis then structural cardiomyopathies. Age, end-diastolic volume index and time-to-CMR showed significant association with the primary endpoint in multi-variate Cox regression. ConclusionsCMR performed early after the onset of clinical symptoms allows discrimination between acute myocardial injury from “true” MINOCA in patients presenting with chest pain and elevated cardiac biomarkers, thereby helping to identify the underlying pathology in suspected MINOCA and allowing risk stratification based on the established diagnosis. Furthermore, CMR parameters allow for improved prediction of adverse events compared to clinical and laboratory parameters.

Blood pressure parameters and the development of congestive heart failure among hypertensive patients at Kiambu County Hospital, Kenya

Introduction: Global incidence of heart failure is on increase. Heart failure has been shown to be on the increase with 1-3% admission rates globally and a 3-7% admission rate in the African hospitals. Hypertension (HTN) has been shown to play a pivotal role in the evolution and syndrome of heart failure where it is mostly non- ischemic in origin yet there are few studies on the association of the individual blood parameters and heart failure.&#x0D; Objective: The study assessed the individual blood pressure parameters as prognosticators of congestive heart failure (CHF) in hypertensive patients.&#x0D; Method: A retrospective study was carried out at Kiambu County Hospital, on 205 heart failure patients who met the Framingham Criteria. The parameters observed included the time of onset of CHF, systolic/ diastolic blood pressure, pulse pressure and their duration to the development of CHF. Multivariable cox proportional hazard regression models were used to determine the effects of individual blood pressure parameters relative to the onset of CHF.&#x0D; Results: Overall, 205 patients were eligible for the study. Median time to CHF was estimated to be 4 years (range: 1-18), median age of CHF development was 65.7 years with a 68.8% female preponderance. Pulse pressure of 55- 60 mm Hg (AHR: 2.21; 95%CI: 1.16-4.21), hypertension duration of 5-10 years (AHR: 0.14; 95%CI: 0.088-0.223) and over 10 years (AHR: 0.023; 95%CI: 0.010-0.050) were significantly associated with the development of CHF.&#x0D; Conclusion: Pulse pressure is a better prognosticator of CHF in hypertensive patients with a hazard ratio of 2.2 times more likely in patients with a pulse pressure of 55- 60 mmHg than those below 55mm Hg.

Abstract 13438: The Role and Mechanism of Chronic Beta3-Adrenergic Receptor Blockade on the Progression of Heart Failure in a Rat Model

Background: The negative inotrope and up-regulation of β 3 -adrenergic receptors (AR) in human and animal failing hearts suggest a direct and contributing role of cardiac β 3 -AR activation on the progression of congestive heart failure (CHF). However, its precise role is still being debated. We hypothesize that up-regulation of cardiac β 3 -AR is detrimental and chronic β 3 -AR blockade may prevent CHF-caused intrinsic defects of left ventricular (LV) myocyte force-generating capacity and relaxation and improve β-AR regulation, thereby limiting the progression of CHF. Methods: We compared the alterations of LV and myocyte functional responses and [Ca 2+ ] i transient ([Ca 2+ ] iT ) in SD rats divided into 3 groups (8/group): 1) CHF 3 months after isoproterenol (ISO) (170 mg/kg, sq, for 2 days); 2) ISO/β 3 -ANT , 2 months after receiving ISO, a selective β 3 -AR antagonist (ANT), L-748,337, was initiated (10 -7 M/kg/day, sq. by mini-pump) and was given for 1 month; and 3) Sham controls . Results: Compared with controls, the animals that received ISO treatment had CHF onset at 1 month and progressed to severe HF at 3 months after ISO. Plasma norepinephrine (NE) (1295 vs 259 pg/ml) increased 5-fold; whereas, stroke volume (SV) (39 vs 91 μl) and ejection fraction (EF) (39 vs 62%) significantly decreased, and LV end-diastolic pressure (P ED ) (13.9 vs 6.0 mmHg) was doubled. These changes were paralleled with about 50% reductions in cell contraction (dL/dt max , 93 vs 186 μm/s) and relaxation (dR/dt max , 96 vs 159 μm/s) associated with a significant decrease in the peak systolic [Ca 2+ ] iT , (0.17 vs 0.26). In addition, superfusion of ISO (10 -8 M) caused much less increases in dL/dt max (39 vs 68%), dR/dt max (23 vs 54%), and [Ca 2+ ] IT (14 vs 28%). Treatment with β 3 -ANT increased SV (89 μl) and EF (60%), decreased P ED more than 90% from ISO-treated values, and corrected the elevation of plasma NE (301 pg/ml), dL/dt max (184 μm/s), dR/dt max (152 μm/s), and [Ca 2+ ] iT (0.24). ISO-induced increase in dL/dt max and [Ca 2+ ] iT also returned close to control levels. Conclusion: Chronic β 3 -ANT treatment after CHF significantly improves LV and myocyte contractile function and [Ca 2+ ] i regulation and limits the development of CHF. Thus, β 3 -AR blocker may provide a new therapeutic strategy for the treatment of CHF.

Early Midterm Results After Valve Replacement With Contemporary Pericardial Prostheses for Severe Aortic Stenosis

Clinical studies have demonstrated improved gradients after aortic valve replacement with the Trifecta (TR) valve (Abbott Cardiovascular, St Paul, MN) as compared with the Carpentier-Edwards Magna Ease (ME) valve (Edwards Lifesciences, Irvine, CA). Clinical benefits of this strategy have not been demonstrated. Patients undergoing aortic valve replacement for severe aortic stenosis with either valve were included. Patients were excluded if they underwent concomitant procedures other than coronary artery bypass grafting. Inverse proportion treatment weighting was used in the analysis. The primary outcome was a composite of cardiac mortality, need for reintervention, and freedom from first congestive heart failure (CHF). Secondary outcomes were all-cause mortality, the composite components, and cumulative CHF admission. Follow-up echocardiograms were assessed in a cohort of patients to assess structural valve degeneration. There were 331 patients in the TR group and 360 patients in the ME group. The TR group had more women (48% vs 32%, P < .001) with smaller roots (left ventricular outflow tract diameter: TR, 2.11 cm; ME, 2.17 cm; P < .001). After weighting there was no significant difference in the composite measure between groups (P > .05). There was no difference in all-cause mortality (hazard ratio, 0.82; 95% confidence interval, 0.42-1.59; P= .56), and 5-year survival was 91.9% in the ME group and 93.4% in the TR group. There was no difference in cardiac death, reintervention, or first onset of CHF or incidence of structural valve degeneration between groups. There was no difference in the rate of admissions for CHF per 100 patients between the 2 valve types (P= .19). Early hemodynamic benefits have not translated into differences in medium-term clinical outcomes between these 2 valves. Long-term follow-up is necessary.

The role of atrial fibrillation as a prognostic factor in doberman pinschers with dilated cardiomyopathy and congestive heart failure

Atrial fibrillation (AF) in congestive heart failure (CHF) is associated with a high risk of mortality and shorter survival times in human and veterinary medicine. A retrospective review of medical records was performed to evaluate the impact of AF on survival times in Doberman Pinschers with dilated cardiomyopathy (DCM). Time of first onset of CHF and its role as a prognostic factor were also determined, as were predictors of AF development.Forty-eight client-owned purebred Doberman Pinschers with DCM and CHF were included; 23 dogs presented with AF and 25 dogs did not develop AF until immediately before cardiac-related death. Dogs with AF survived for significantly shorter times than those without AF (P = 0.043). For dogs with AF, mean and median survival times were 88.2 days and 22 days, respectively (range, 42.1–134.4 days); mean and median survival times for dogs without AF were 150.7 days and 98 days, respectively (range, 98.5–203 days). AF increased the risk of cardiac-related death (hazard ratio [HR], 2.371; 95% confidence intervals [CI], 1.14–4.95; P = 0.021). Biventricular and right atrial dilation was only present in dogs with AF and right atrial enlargement was the only significant predictor of AF after multivariate analysis (P < 0.001). Dogs with AF had significantly higher mean heart rates than dogs without AF (201 beats per min [bpm] vs. 132 bpm; P < 0.001). In conclusion, AF in Doberman Pinschers with DCM and CHF increased the risk of cardiac-related death and reduced survival time.

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

BackgroundThe 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).ObjectivesTo 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.AnimalsOne hundred and thirty‐five, and 73 dogs that did or did not develop CHF, respectively.Materials and methodsThe 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.ResultsThe 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 ImportanceDogs 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.

IMPACT OF DIFFERENT ANGIOTENSIN-CONVERTING INHIBITORS ON OUTCOMES OF POST-MYOCARDIAL INFARCTION PATIENTS

The aim: To compare the long-term effects of different angiotensin-converting enzyme inhibitors in post-myocardial infarction (MI) patients. Materials and methods: Of 445 consecutive patients with myocardial infarction, 76 (17%) patients had co-morbid conditions, as well as were found to be compliant with secondary prevention treatment and eligible for follow-up. These patients were assigned to ramipril, perindopril or zofenopril groups in complex management of post-MI period. Subsequently, the patients were followed-up prospectively for a period of up to 24 months. Results: Patients of zofenopril group performed better in terms of post-MI biventricular remodeling and left ventricular function recovery. Also, patients receiving zofenopril showed benefits in terms of short-term and long-term mortality as compared with patients of ramipril and perindopril groups. Conclusion: Zofenopril may have advantages over perindopril and ramipril in the complex management of post-MI patients in terms of prevention of negative myocardial remodeling, onset of congestive heart failure and major adverse events.

P1560Prognostic predictors of mortality in very elderly patients presenting with NSTEMI

Abstract Background Elderly patients are usually under-represented in randomized controlled trials, therefore there is less data providing prognostic information for this particular group. NSTEMI clinical practice guidelines indicate that older patients should receive the same therapeutic strategy than younger patients. Methods Observational retrospective study including 8771 patients admitted for acute coronary syndrome in two tertiary referral hospitals between 2003 and 2017: 5673 NSTEMI (64.3%) and 3098 STEMI (35.7%). 999 patients presenting with NSTEMI and aged over 75 years were selected and divided into 3 groups: aged 75–80, aged 80–89 and aged over 90. Cox proportional hazard regression analysis was performed in order to determine independent predictors of mortality. Mortality and survival were represented by Kaplan-Meier curves and log rank test was conducted to assess significant differences in survival between groups. Median follow-up period was 48 months. Results A significant association between female sex and elder age was observed, also a higher prevalence of hyperlipemia and diabetes. In acute phase, no significant differences were found in between congestive heart failure onset, myocardial re-infarction, acute renal failure, stroke or in-hospital mortality amongst the 3 groups. However, at follow-up period, higher mortality in elder groups was documented. After performing a multivariate analysis, age was identified as an independent predictor of mortality at follow-up (&lt;90 years: HR 1.50 CI 95% 1.23–1.83, p=0.0001, &gt;90 years: HR 1.93 CI 95% 1.27–2.93, p=0.002) as well as GRACE score (HR 1.06, CI 95% 1.02–1.09, p=0.002), CRUSADE score (HR 1.01 CI 95% 1.01–1.02, p=0.0001) and treatment with digoxine (HR 1.38 CI 95% 0.95–2.0, p=0.08). On the other side, beta-blockers (HR 0.71 CI 95% 0.59–0.86, p=0.0001) and complete coronary revascularization (HR 0.48 CI 95% 0.37–0.64, p=0.0001) were found to be protective factors. Conclusions In very elderly patients presenting with NSTEMI, prognostic predictors of mild-term mortality are similar to those present in younger patients. Recommendations of clinical practice guidelines, such as beta-blockers' treatment and coronary revascularization, should also be applied in elderly patients.

Reactivation of Chagas disease among heart transplant recipients in the United States, 2012-2016.

Heart transplantation has been shown to be a safe and effective intervention for progressive cardiomyopathy from chronic Chagas disease. However, in the presence of the immunosuppression required for heart transplantation, the likelihood of Chagas disease reactivation is significant. Reactivation may cause myocarditis resulting in allograft dysfunction and the rapid onset of congestive heart failure. Reactivation rates have been well documented in Latin America; however, there is a paucity of data regarding the risk in non-endemic countries. We present our experience with 31 patients with chronic Chagas disease who underwent orthotopic heart transplantation in the United States from 2012 to 2016. Patients were monitored following a standard schedule. Of the 31 patients, 19 (61%) developed evidence of reactivation. Among the 19 patients, a majority (95%) were identified by laboratory monitoring using polymerase chain reaction testing. One patient was identified after the onset of clinical symptoms of reactivation. All subjects with evidence of reactivation were alive at follow-up (median: 60weeks). Transplant programs in the United States are encouraged to implement a monitoring program for heart transplant recipients with Chagas disease. Our experience using a preemptive approach of monitoring for Chagas disease reactivation was effective at identifying reactivation before symptoms developed.