MANAGEMENT OF ATRIAL FIBRILLATION, VENTRICULAR ARRHYTHMIA, LEFT VENTRICULAR DYSFUNCTION, AND SUBSEQUENT CARDIOPATHOLOGIC EVALUATION IN AN ORANGUTAN (PONGO PYGMAEUS × ABELII).

A 37-yr-old male vasectomized hybrid orangutan (Pongo pygmaeus × abelii) was diagnosed with left ventricular dysfunction during a preventative health care examination. Treatment was initiated with carvedilol. The following year, this orangutan was evaluated for intermittent lethargy. Following observation of an irregular cardiac rhythm during an echocardiogram, a lead II electrocardiogram revealed atrial fibrillation and ventricular arrhythmia. Additional treatment included amiodarone, furosemide, spironolactone, clopidogrel, and aspirin. An improved activity level was noted, and follow-up testing showed restoration of a sinus rhythm, reduced frequency of ventricular arrhythmia, and improved left ventricular function. The orangutan died 27 mon after initial diagnosis of heart disease, and a complete necropsy was performed. This article describes successful diagnosis and management of structural and arrhythmic heart disease in an orangutan, emphasizing the role of cardiac disease screening and behavioral training in apes, as well as the value of matching thorough antemortem and postmortem cardiac evaluation.

The aorta in humans and African great apes, and cardiac output and metabolic levels in human evolution.

Humans have a larger energy budget than great apes, allowing the combination of the metabolically expensive traits that define our life history. This budget is ultimately related to the cardiac output, the product of the blood pumped from the ventricle and the number of heart beats per minute, a measure of the blood available for the whole organism physiological activity. To show the relationship between cardiac output and energy expenditure in hominid evolution, we study a surrogate measure of cardiac output, the aortic root diameter, in humans and great apes. When compared to gorillas and chimpanzees, humans present an increased body mass adjusted aortic root diameter. We also use data from the literature to show that over the human lifespan, cardiac output and total energy expenditure follow almost identical trajectories, with a marked increase during the period of brain growth, and a plateau during most of the adult life. The limited variation of adjusted cardiac output with sex, age and physical activity supports the compensation model of energy expenditure in humans. Finally, we present a first study of cardiac output in the skeleton through the study of the aortic impression in the vertebral bodies of the spine. It is absent in great apes, and present in humans and Neanderthals, large-brained hominins with an extended life cycle. An increased adjusted cardiac output, underlying higher total energy expenditure, would have been a key process in human evolution.

Surgical placement of implantable cardiac loop recorders in great apes.

Cardiovascular disease is the leading cause of morbidity and mortality in zoologically managed adult great apes, accounting for 29%-77% of adult deaths in the North American population depending on the species. In an effort to better understand the underlying causes of heart disease, implantable loop recorders (ILRs) have been used in some cases to monitor great apes with suspected or known cases of arrhythmia. This is a 10-year review of the Great Ape Heart Project's experience of implanting 21 ILRs in 7 gorillas (Gorilla gorilla gorilla; 9 total ILR devices), 5 chimpanzees (Pan troglodytes, 11 total ILR devices), and 1 orangutan (Pongo abelii, 1 ILR device) in an effort to develop effective methods for surgical implantation and remote collection of the data for analysis.

Conduction system pacing in prosthetic heart valves.

BACKGROUND: There has been increasing interest in physiologic pacing techniques that directly activate the specialized conduction system. We aimed to assess outcomes of conduction system pacing (CSP) in patients with prosthetic heart valves. METHODS: This systematic review was performed according to PRISMA guidelines. Freeman-Tukey double arcsine transformation with the random-effect model was used to summarize the data. Outcomes studied were 1) implant success (defined as ability to recruit the His-Purkinje system or the distal Purkinje system); (2) lead parameters at implant and follow-up; and (3) procedure-related complications. RESULTS: This systematic review of 7 studies included 267 unique patients in whom CSP was attempted with either HBP or LBBAP for pacing indications after a prosthetic valve. HBP was attempted in 38% (n = 108), while LBBAP in 62% (n = 175) patients. The overall success rate of CSP was 87%, while in patients post-TAVR, the overall success rate was 83.2%. In the subgroup analysis, LBBAP had a significant higher overall success rate compared to HBP (94.3% vs. 76.5%, p interaction = 0.02) and post-TAVR patients (94.3 vs. 66.9%, p interaction < 0.01), respectively. The LBBAP thresholds were significantly lower compared to HBP both at implant (0.67 ± 0.4 @ 0.44 ms vs. 1.35 ± 1 @ 0.85 ms, p interaction < 0.01) and at a mean follow-up of 12.4 ± 8 months (0.73 ± 0.1 @ 0.44 ms vs. 1.39 ± 1 @ 0.85 ms, p interaction < 0.01), respectively. CONCLUSION: CSP is safe and feasible in patients with a prosthetic valve, with a significantly higher success rate and superior lead parameters with LBBAP than HBP, especially in patients post-TAVR.

Navigating inferior vena cava filters in invasive cardiology procedures: A systematic review.

BACKGROUND: Transfemoral venous access (TFV) is the cornerstone of minimally invasive cardiac procedures. Although the presence of inferior vena cava filters (IVCFs) was considered a relative contraindication to TFV procedures, small experiences have suggested safety. We conducted a systematic review of the available literature on cardiac procedural success of TFV with IVCF in-situ. METHODS: Two independent reviewers searched PubMed, EMBASE, SCOPUS, and Google Scholar from inception to October 2020 for studies that reported outcomes in patients with IVCFs undergoing TFV for invasive cardiac procedures. We investigated a primary outcome of acute procedural success and reviewed the pooled data for patient demographics, procedural complications, types of IVCF, IVCF dwell time, and procedural specifics. RESULTS: Out of the 120 studies initially screened, 8 studies were used in the final analysis with a total of 100 patients who underwent 110 procedures. The most common IVCF was the Greenfield Filter (36%), 60% of patients were males and the mean age was 67.8 years. The overall pooled incidence of acute procedural success was 95.45% (95% confidence interval = 89.54-98.1) with no heterogeneity (I2 = 0%, p = 1) and there were no reported filter-related complications. CONCLUSION: This systematic review is the largest study of its kind to demonstrate the safety and feasibility of TFV access in a variety of cardiac procedures in the presence of IVCF.

Species-Spanning Echocardiography: Cardiovascular Insights from Across the Animal Kingdom.

PURPOSE OF REVIEW: The objective of this review is to present comparative echocardiography as a source of insights for human cardiovascular medicine. RECENT FINDINGS: We present echocardiographic examples of high impact human cardiovascular pathologies, including valvular, vascular, conduction, and myocardial disorders, in a wide range of species in varying environments. Unique features associated with comparative echocardiographic assessments are linked to human cardiology, including natural animal models of resistance and vulnerability. The cardiovascular vulnerabilities and strengths of other species can be a source of invaluable insights for human healthcare professionals. Echocardiography is playing a key role in bridging human and veterinary cardiology. Consequently, species-spanning echocardiography can deliver novel insights for human medicine.

Monitoring great ape heart health through innovative electrocardiogram technology: Training methodologies and welfare implications.

Assessing and treating cardiovascular disease (or heart disease) is a growing concern for institutions housing great apes, as it is a major cause of mortality in all four taxa managed in human care. As part of a proactive monitoring plan, zoological managers and veterinarians often elect to perform electrocardiograms (ECGs) on their great ape populations. ECGs noninvasively evaluate cardiac electrical activity, and are thereby capable of providing information regarding heart function. This electrical signature is transcribed as a visual display of waveforms, referred to as telemetry strips, and can detect irregularities in heart rhythm, also known as arrhythmia. While traditional 6- or 12-lead ECGs are recommended periodically as part of a thorough heart performance evaluation, here we discuss the KardiaMobile (KM) device as an additional primate welfare tool. KM is a small, Food and Drug Administration-cleared, clinical-grade mobile ECG monitor that requires only 30 s of pressure to flag heart rate or arrhythmic abnormalities. We detail the training process and applicability to great apes in human care.

GREAT APE HEART PROJECT GUIDELINES FOR THE ECHOCARDIOGRAPHIC ASSESSMENT OF GREAT APES.

Cardiovascular disease (CVD) has been identified as a major cause of mortality in all four great ape taxa in zoologic institutions. In an effort to better understand and treat CVD in captive great apes, a program called the Great Ape Heart Project (GAHP), based at Zoo Atlanta, collects and maintains a database of echocardiograms and other relevant medical information relating to the cardiac health status of great apes. Cardiac health assessments have become standard practice among North American zoos that house great apes and are recommended by all four great ape Species Survival Plans (SSP) for the assessment of CVD in captive great apes. As of December 31, 2017, more than 70 ape-holding institutions have submitted approximately 1,100 cardiac examinations of great apes to the GAHP, information from which is stored in the GAHP database. Transthoracic echocardiography is one of the most practical and cost-effective diagnostic imaging techniques for the evaluation of cardiac function in great apes. Standardization of echocardiographic measurements is critical for maximizing the diagnostic value of an echocardiographic exam and for utilization of stored information in comparative studies within and between the great ape taxa. The following manuscript offers suggestions for standardization of nomenclature, imaging technique, echocardiographic measurements, data storage, and reporting of cardiac exams for submission into the GAHP database with the goal of promoting consistency and quality in data collection.

Cardiac disease is linked to adiposity in male gorillas (Gorilla gorilla gorilla).

Cardiac disease is a major cause of morbidity and mortality for adult gorillas. Previous research indicates a sex-based difference with predominantly males demonstrating evidence of left ventricular hypertrophy. To evaluate these findings, we analyzed serum markers with cardiac measures in a large sample of gorillas. The study sample included 44 male and 25 female gorillas housed at American Association of Zoo and Aquariums (AZA)-accredited zoos. Serum samples were collected from fasted gorillas during routine veterinary health exams and analyzed to measure leptin, adiponectin, IGF-1, insulin, ferritin, glucose, triglycerides, and cholesterol. Cardiac ultrasonography via transthoracic echocardiogram was performed simultaneously. Three echocardiographic parameters were chosen to assess cardiac disease according to parameters established for captive lowland gorillas: left ventricular internal diameter, inter-ventricular septum thickness, and left ventricular posterior wall thickness. Our data revealed that high leptin, low adiponectin, and lowered cholesterol were significantly and positively correlated with measures of heart thickness and age in males but not in females. Lowered cholesterol in this population would be categorized as elevated in humans. High leptin and low adiponectin are indicative of increased adiposity and suggests a potential parallel with human obesity and cardiovascular disease in males. Interestingly, while females exhibited increased adiposity with age, they did not progress to cardiac disease.

Diagnosing cardiovascular disease in western lowland gorillas (Gorilla gorilla gorilla) with brain natriuretic peptide.

Cardiovascular disease is a leading cause of death in zoo-housed great apes, accounting for 41% of adult gorilla death in North American zoological institutions. Obtaining a timely and accurate diagnosis of cardiovascular disease in gorillas is challenging, relying on echocardiography which generally requires anesthetic medications that may confound findings and can cause severe side effects in cardiovascularly compromised animals. The measurement of brain natriuretic peptide (BNP) has emerged as a modality of interest in the diagnosis, prognosis and treatment of human patients with heart failure. This study evaluated records for 116 zoo-housed gorillas to determine relationships of BNP with cardiovascular disease. Elevations of BNP levels correlated with the presence of visible echocardiographic abnormalities, as well as reported clinical signs in affected gorillas. Levels of BNP greater 150 pb/mL should alert the clinician to the presence of myocardial strain and volume overload, warranting medical evaluation and intervention.

Figure-of-eight suture for venous hemostasis in fully anticoagulated patients after atrial fibrillation catheter ablation.

INTRODUCTION: Limited data exists for types of venous closure and its associated complications in patients after atrial fibrillation (AF) catheter ablation. We evaluated the subcutaneous figure-of-eight closure (FO8) for achieving venous hemostasis after AF catheter ablation compared to manual pressure. METHODS: 284 consecutive patients that underwent AF catheter ablation by two operators were included. All patients received continuous therapeutic warfarin or interrupted novel oral anticoagulants (NOAC) and heparin (ACT300-400 s) without reversal. Patients were divided into two groups: 1) sheaths were left in place and pulled once ACT < 180 s, with hemostasis being achieved with manual pressure (MP); and 2) a subcutaneous FO8 suture closed the venous access site immediately after the ablation on each groin site and sheaths were removed immediately after the ablation despite full anticoagulation with heparin and warfarin or interrupted NOAC. Sutures were removed after four hours, and the patients laid flat for an additional two hours. RESULTS: The MP group (n = 105) was similar to the FO8 group (n = 179). Time in bed was 573 ± 80 min for MP group vs. 373 ± 49 min for FO8 group (p < 0.0001). Eleven hematomas were seen in the MP group compared to seven in the FO8 group (P = 0.041). CONCLUSIONS: In fully anticoagulated patients undergoing AF catheter ablation, excellent hemostasis was achieved with figure-of-eight sutures, with no major vascular complications, a lower hematoma rate, and a significantly shorter flat-time-in-bed compared to manual pressure.

Incidence of Pocket Infection Postcardiac Device Implantation Using Antibiotic versus Saline Solution for Pocket Irrigation.

BACKGROUND: Preprocedure systemic antibiotic prophylaxis reduces infections in patients undergoing cardiac implantable electronic devices (CIEDs) implantations. Whether pocket irrigation with antibiotic solution offers any advantage over saline solution in CIED implantation is unknown. METHODS: Records from 327 consecutive patients who underwent CIED implantation by three operators from February 2011 to January 2014 were reviewed. From February 2011 to January 2012, the antibiotic solution was used for pocket irrigation; from February 2012 to January 2014, saline solution was used. All patients received preprocedural IV antibiotics. Baseline demographics, comorbidities, lab data, and occurrence of any pocket infection postimplant were collected. RESULTS: There were 118 and 209 patients in the antibiotic solution and saline solution group, respectively. A total of four (1.2%) patients had CIED infection: two in the antibiotic solution group and two in the saline solution group. Median time to infection from implant date was 81.5 ± 35 days. Two patients (50%) had infection after first device implantation. Of the four patients, one had positive blood culture, three had positive pocket cultures, one had lead vegetation, one underwent pocket exploration, and all of them had devices/leads extracted, with reimplantation on the contralateral side. No mortality was observed due to infectious complications. CONCLUSION: When compared to pocket irrigation in the antibiotic solution group, the saline solution group was not associated with increased incidence of infectious complications after CIED implantation. The use of saline solution pocket irrigation alone may be used in CIED pocket irrigation periprocedurally.  Further evaluation in larger randomized trials is needed.

Pulmonary Vein Isolation Using the Visually Guided Laser Balloon: A Prospective, Multicenter, and Randomized Comparison to Standard Radiofrequency Ablation.

BACKGROUND: Balloon catheters have been designed to facilitate pulmonary vein (PV) isolation in patients with paroxysmal atrial fibrillation (AF). The visually guided laser balloon (VGLB) employs laser energy to ablate tissue under direct visual guidance. OBJECTIVES: This study compared the efficacy and safety of VGLB ablation with standard irrigated radiofrequency ablation (RFA) during catheter ablation of AF. METHODS: Patients with drug-refractory paroxysmal AF were enrolled in a multicenter, randomized controlled study of PV isolation using either the VGLB or RFA (control). The primary efficacy endpoint was freedom from protocol-defined treatment failure at 12 months, including symptomatic AF occurring after the 90-day blanking period. The primary efficacy and safety endpoints were powered for noninferiority. RESULTS: A total of 353 patients (178 VGLB, 175 control) were randomized at 19 clinical sites. The mean procedure, ablation, and fluoroscopy times were longer with VGLB compared with controls. The primary efficacy endpoint was met in 61.1% in the VGLB group versus 61.7% in controls (absolute difference -0.6%; lower limit of 95% confidence interval [CI]: -9.3%; p = 0.003 for noninferiority). The primary adverse event rate was 11.8% in the VGLB group versus 14.5% in controls (absolute difference -2.8%; upper limit of 95% CI: 3.5; p = 0.002 for noninferiority), and was mainly driven by cardioversions. Diaphragmatic paralysis was higher (3.5% vs. 0.6%; p = 0.05), but PV stenosis was lower (0.0% vs. 2.9%; p = 0.03) with VGLB. CONCLUSIONS: Despite minimal prior experience, the safety and efficacy of VGLB ablation proved noninferior to RFA for the treatment of paroxysmal AF. (Pivotal Clinical Study of the CardioFocus Endoscopic Ablation System-Adaptive Contact [EAS-AC] [HeartLight] in Patients With Paroxysmal Atrial Fibrillation [PAF] [HeartLight]; NCT01456000).

Evaluating echocardiogram and indirect blood pressure results in male western lowland gorillas (Gorilla gorilla gorilla) during three phases of an anesthetic protocol.

Until the majority of the great ape population is trained for conscious cardiac evaluations, most individuals will require general anesthesia to perform echocardiograms. Within the veterinary community, concern exists that certain anesthetic protocols may exacerbate or artificially induce signs of cardiac disease. Because of potential cardiovascular effects, medetomidine has generally been used cautiously in patients with cardiac disease. The combination of ketamine and medetomidine is frequently used by many institutions because of its reversibility. To date, no published studies have obtained physiologic or echocardiographic parameters comparing different anesthetic protocols. In this study, with the use of seven adult male gorillas (Gorilla gorilla gorilla) with and without cardiac disease, echocardiographic and indirect blood pressure data during three phases of an anesthetic protocol were collected. The initial echocardiographic study was completed with ketamine/ medetomidine alone (5-7 mg/kg, i.m., and 0.05-0.07 mg/kg, i.m., respectively); the second study was completed after the addition of sevoflurane inhalant anesthesia to this procedure; and the third study was completed after reversal of medetomidine by administration of atipamezole (5:1 with the medetomidine dose given at induction). Without exception, ejection fractions were 15-25% lower under anesthesia with medetomidine as compared to ejection fractions after administration of atipamezole. Indirect blood pressures were higher on ketamine/ medetomidine, lower with addition of sevoflurane, and considerably lower after administration of atipamezole.

Echocardiographic parameters of captive western lowland gorillas (Gorilla gorilla gorilla).

A total of 163 echocardiographic studies on western lowland gorillas (Gorilla gorilla gorilla) were submitted for evaluation; 140 from 99 animals were suitable for analysis. Of these, 81 studies (42 studies from 35 males ranging in age from 11-41+ yr and 39 studies from 31 females ranging in age from 11-41+ yr) are reported here. Three studies from 3 females and 56 studies from 30 males were excluded from this report due to cardiac abnormalities. Cardiac parameters measured were aortic root (Ao Rt) diameter and left atrial (L atrium) size. Left ventricular (LV) measurements included left ventricular internal diameter in systole (LVID(s)) and diastole (LVID(d)) as well as diastolic septal (IVS) and posterior wall thickness (LVPW). Values considered to be normal in females > 11 yr of age were: Ao Rt < 3.5 cm, L atrium < 4.0 cm, LVID(d) < 5.0 cm, IVS < 1.4 cm, LVPW < 1.4 cm, and ejection fraction (EF) > 60%. The data from male gorillas show a separation in animals based on three cardiac parameters: systolic function, LV cavity size, and LV wall thickness. Male gorillas > 11 yr of age fall into two groups; unaffected and affected. Unaffected animals are defined as those with no echocardiographic abnormalities and a consistent Ao Rt of < 4.0 cm, LVID(d) of < 6.0 cm, IVS and LVPW of <1.5 cm, and an EF of > 58%. The affected group consisted of male gorillas that exhibited changes in echocardiographic parameters representing the presence of cardiovascular disease. The results determined in this database, gathered from data collected from 1999-2009, suggest a sex-based difference between males and females with predominantly males demonstrating evidence of cardiac disease. The most striking finding seen in this study is that of progressive LV hypertrophy and depressed LV EF in affected adult male gorillas.

Risk of hematoma complications after device implant in the clopidogrel era.

BACKGROUND: Device implant pocket hematoma is a recognized complication after permanent pacemaker (PM) and implantable cardioverter-defibrillator (ICD) implantation. Pocket hematoma is associated with local discomfort, an increased risk of infection, and may require surgical intervention or lead to lengthier hospital stays. The purpose of the study was to identify the clinical factors associated with hematoma formation after PM or ICD device implantation. METHODS AND RESULTS: The subjects of this prospective observational study were 935 consecutive patients at Beaumont Hospital who underwent implantation of a PM or an ICD. Clinical characteristics and anticoagulant/antiplatelet drug use were recorded. A pocket hematoma was documented in 89 of 935 patients. Significant predictors of device pocket hematoma included ongoing clopidogrel therapy (18.3% on therapy, 10.5% recently discontinued, and 7.9% off therapy; P<0.001) and use of intravenous heparin (22.0% on therapy versus 8.2%; P<0.0001). Patients in whom clopidogrel was discontinued >4 days before device implantation had no hematoma. Hematomas occur more frequently in patients receiving ICDs than those receiving PMs. Device pocket hematoma was associated with an increased median length of hospital stay (4 days [interquartile range, 1 to 9] days with versus 2 days [ interquartile range, 1 to 6] days without hematoma; P=0.004) and increased late complications or surgical intervention. CONCLUSIONS: The use of clopidogrel or intravenous heparin significantly increased the risk of hematoma at the time of PM or ICD implantation. By withholding clopidogrel before surgery, the excess risk of bleeding complications may be reduced.

Dose-related effects of methadone on QT prolongation in a series of patients with torsade de pointes.

STUDY OBJECTIVE: To investigate the relationship between the daily dose of the synthetic opioid methadone and the corrected QT (QTc) interval in a series of methadone-treated patients who developed torsade de pointes. DESIGN: Retrospective case series analysis. SETTING: Outpatient pain management center and methadone maintenance treatment programs. PATIENTS: Seventeen patients who developed torsade de pointes while receiving very high daily doses of methadone. MEASUREMENTS AND MAIN RESULTS: The QTc intervals were calculated for each patient. The relationship between daily methadone dose and QTc interval was assessed and adjusted for clinical characteristics that may have independently prolonged cardiac repolarization. The mean QTc interval was 615 +/- 77 msec. Multiple linear regression indicated that only the daily methadone dose was predictive of the QTc interval (r = +0.51, p = 0.03). All other variables examined, such as age, sex, presence of hypokalemia or structural heart disease, and presence of QT-prolonging drugs, were not predictive of the QTc interval (minimum p = 0.28). CONCLUSION: In this series, the daily methadone dose correlated positively with the QTc interval. This finding supports the possibility that methadone contributed to the development of arrhythmia.

Negative-pressure pulmonary edema complicated by acute respiratory distress syndrome in an orangutan (Pongo pygmaeus abelii).

A 22-yr-old, 86-kg, morbidly obese female orangutan (Pongo pygmaeus abelii) was immobilized and transported to the Denver Zoological Gardens hospital for a routine physical examination. Immediately after arriving at the hospital, cyanosis and apparent inadequate ventilatory efforts were noted. Clinically significant hypoxia occurred despite attempts to ventilate the orangutan through face mask, and attempts to place an endotracheal tube began. A large volume of pink-tinged frothy fluid flowed from the trachea when the laryngoscope was inserted into the oropharynx. Severe pulmonary edema due to negative-pressure pulmonary edema, precipitating life-threatening hypoxia was suspected. The orangutan was maintained on a mechanical ventilator using the neuromuscular blocking agent cisatracurium besylate and sedation with periodic doses of isoflurane and midazolam for 48 hr. Positive end-expiratory pressure was used while the orangutan was ventilated mechanically to improve respiratory function. The edema and hypoxia improved, but respiratory arrest ensued 30 min after extubation, when the orangutan was removed from mechanical ventilation. Necropsy and histopathology demonstrated that serious lung injury had led to acute respiratory distress syndrome.