Ex-vivo histopathologic examination of irrigated radiofrequency ablation utilizing half-normal saline of the human heart.

INTRODUCTION: Radiofrequency ablation (RFA) utilizing half-normal saline (HNS) irrigation is a promising intervention to circumvent commonly encountered limitations during radiofrequency ablation of deep myocardial substrate. Few studies to date have analyzed the morphologic changes in the human myocardium following HNS RFA. METHODS AND RESULTS: Three patients with symptomatic ventricular tachycardia (VT) who underwent RFA with HNS irrigation underwent pathological specimen examination at time of autopsy or following native heart explant at the time of cardiac transplantation. Gross evaluation of the heart was performed fresh and after fixation in 10% formalin. A routine examination was performed with fixation in 10% formalin. Sections of lesioned tissue were paraffin embedded and evaluated using standard hematoxylin and eosin (H&E) staining. CONCLUSION: Irrigated RF ablation with HNS irrigant produces coagulative necrosis as well as several delayed histopathological changes with a deeper field of effective ablation. Transmurality may not be obtained in the ventricular myocardium with endocardial, epicardial, or sequential unipolar HNS ablation.

Isolated aortic valve replacement with bio-prostheses in patients age 50 to 65 years: a decade of statewide data on cost and patient outcomes.

BACKGROUND: Guidelines for choice of replacement valve-mechanical versus bio-prosthetic, are well established for patients aged <50 and >65 years. We studied the trends and implications of aortic valve replacement (AVR) with mechanical versus bioprosthetic valve in patients aged 50 to 65 years. METHODS: STS and cost database of 17 centers for isolated AVR surgery were analyzed by dividing them into bioprosthetic valve (BV) or mechanical valve (MV) groups. RESULTS: From 2002 to 2011, 3,690 patients had AVR, 18.6% with MV and 81.4% with BV. Use of BV for all ages increased from 71.5% in 2002 to 87% in 2011. There were 1127 (30.5%) patients in the age group 50-65 years. Use of BV in this group almost doubled, 39.6% in 2002 to 76.8% in 2011. Mean age of patients in BV group was higher (59.2±4.2 years vs. 56.7±4.3 years, P≤0.0001). Preoperative renal failure, heart failure and chronic obstructive pulmonary disease favored use of BV, whereas preoperative atrial fibrillation favored AVR with MV. Mortality (MV 2.2% vs. BV 2.36%) and other postoperative outcomes between the groups were similar. Cost of valve replacement increased for both groups (MV $26,191 in 2002 to $42,592 in 2011; BV $27,404 in 2002 to $44,257 in 2011). CONCLUSIONS: Use of bioprostheses for AVR has increased; this change is more pronounced in patients aged 50-65 years. Specific preoperative risk factors influence the choice of valve for AVR. Postoperative outcomes between the two groups were similar. Long-term implications of this changing practice, in particular, reoperation for bioprosthetic valve degeneration should be examined.

Combined Heart-Liver and Domino Liver Transplantation in Familial Amyloidosis.

BACKGROUND: Combined heart-liver transplantation (CHLT) is the only curative option for patients with concomitant pathology affecting the heart and liver. In some cases, the native livers of familial amyloidosis (FA) patients may be suitable for domino transplantation into other recipients. METHODS: Retrospective analysis (2013 to 2019) of all CHLT at our center was performed. Continuous data were presented as mean with standard deviation and discrete variables as percentages. RESULTS: Familial amyloidosis was the indication for CHLT in 5 out of 6 patients. The mean recipient age was 55 ± 5.62 years. Two patients were bridged with total artificial heart. The mean model for end-stage liver disease score at transplant was 17.17 ± 3.7. Two explanted livers were used for transplantation in a domino fashion. The median intensive care and hospital stays were 5.5 and 19 days, respectively. Complications included renal failure (1), groin abscess (1), pulmonary embolism (1), and cardiac rejection (1). Patient and graft survival for both organs was 100% at a median follow-up of 59 (range 20-76) months. DISCUSSION: Combined heart-liver transplantation for FA achieves excellent outcomes. The possible use of livers explanted from patients with FA for domino liver transplantation can contribute to the liver donor pool.

Spectrum of arrhythmogenic substrate post minimally invasive maze surgery in patients with recurrent.

BACKGROUND: Advancements in minimally invasive surgical ablation (MISA) have focused on improving pulmonary vein isolation. Additional ablation targets have been developed (such as posterior wall isolation). The mid- and long-term effects of current techniques (including electrophysiologic findings and recurrent arrhythmia mechanisms) have not previously been reported. METHODS: Twenty eight patients with recurrent atrial arrhythmias after bipolar clamp ablation of the pulmonary vein antrum, ganglionated plexi, posterior wall isolation (roof and floor lines to create a posterior box), and ligament of Marshall ligation/cauterization and left atrial appendage clipping underwent follow up electrophysiology study including left atrial mapping an average of 2.3 years postoperatively. RESULTS: Atrial fibrillation was the most common recurrent arrhythmia (n = 18) followed by micro-reentrant atrial tachycardia (n = 5), macro-reentry left atrial flutter (n = 3), and typical cavo-tricuspid isthmus atrial flutter (n = 2). Eighty six of 112 (77%) PVs mapped were electrically isolated, 16 (57%) patients had all four pulmonary veins (PVs) isolated. The posterior wall (PW) was completely isolated in only four (14%) patients, seven (25%) patients had normal PW voltage, while 17 (61%) patients had abnormal delayed or fractionated electrograms in the posterior wall (incomplete isolation). Abnormal PW electrograms were more frequently found in patients with complex recurrent left atrial arrhythmia (micro-reentry or left atrial macro-reentry flutter). CONCLUSION: With current surgical techniques PV isolation has improved, but PW isolation remains challenging. Incomplete PW isolation may produce arrhythmogenic substrate.

Predictors of Renal Failure in Patients Treated With the Total Artificial Heart.

BACKGROUND: The incidence of hemodialysis (HD)-dependent renal failure after total artificial heart (TAH) implantation is high. We sought to determine the preoperative predictors of HD after TAH implantation. METHODS AND RESULTS: We studied 87 patients after TAH implantation at our institution between April 2006 and March 2017. Baseline clinical data were obtained from the medical records, and patients were followed until death or heart transplantation. We performed logistic regression analysis to identify predictors of HD after TAH implantation. Of the patients, 24 (28%) required postimplantation HD. Those requiring HD were more likely to have histories of coronary artery disease (58% vs 29%; P = 0.01), required preoperative membrane oxygenation (33% vs 4.8%; P = 0.001) and had lower baseline estimated glomerular filtration rates (54 ± 29 vs 67 ± 24 mL/min/1.73m2; P = 0.04). Patients requiring HD were at a higher risk of death on device at 1 year (33% vs 5%, P = 0.001; log rank test: P =0.001, hazard ratio 6.6 [95% CI:1.8-23], P = 0.003). CONCLUSIONS: The incidence of postimplantation HD is high and is associated with increased likelihood of mortality. Lower baseline estimated glomerular filtration rates, histories of coronary artery disease and preoperative membrane oxygenation support are predictors of postimplantation requirement of HD. These data may help to identify patients at risk for adverse outcomes after TAH implantation.

Neurologic Complications in Patients with Left Ventricular Assist Devices: Single Institution Retrospective Review.

BACKGROUND: Neurologic complications are common complications encountered by patients with left ventricular assist devices (LVADs). This single-center retrospective study aims to identify the incidence and risk factors of neurologic complications and interventions in patients supported with LVADs and define the associated anticoagulation management. METHODS: Between August 2009 and August 2017, 244 patients underwent LVAD implantation. Twenty-one patients were excluded for having neurologic complications before LVAD placement or for having previously undergone heart transplantation. RESULTS: Fifty-six patients (25%) suffered 61 complications, and 11 (19.6%) died as a result. Gender, type of LVAD, or chronic medical comorbidities evaluated did not contribute to a difference in complication rate; in contrast, length of LVAD implantation was directly related to risk of neurologic complication. Eleven patients (19.6%) underwent 13 surgical interventions including 5 mechanical thrombectomies. Anticoagulation was reversed in 16 patients and held without complication. Anticoagulation was not held for ischemic complications, and no clinically significant hemorrhagic transformation occurred. Intravenous tissue plasminogen activator was also successfully administered to 3 patients without complication. CONCLUSIONS: Neurologic complications were observed in 25% of patients supported with LVADs, of which 20% required neurosurgical intervention. Anticoagulation can be safely withheld in patients with hemorrhagic complications. Patients with ischemic complications can continue to be anticoagulated with no significant risk of hemorrhagic transformation. Length of LVAD implantation was directly related to the risk of neurologic complication. Finally, our study adds to existing literature that mechanical thrombectomy and even intravenous tissue plasminogen activator are options for LVAD patients with ischemic complications.

Heart transplantation from donation after circulatory death donors: Present and future.

The first successful human heart transplantation was reported on 3 December 1967, by Christiaan Barnard in South Africa. Since then this life-saving procedure has been performed in over 120 000 patients. A limitation to the performance of this procedure is the availability of donor hearts with as many as 20% of patients dying before a donor's heart is available for transplant. Today, hearts for transplantation are procured from individuals experiencing donation after brain death (DBD). Interestingly, this, however, was not always the case as the first heart transplants occurred after circulatory death. Revisiting the availability of hearts for transplant from those experiencing donation after circulatory death (DCD) could further expand the number of hearts suitable for transplantation. There are several considerations pertinent to transplanting hearts from those undergoing circulatory death. In this review, we summarize the main distinctions between DBD and DCD heart donation and discuss the research relevant to increasing the number of hearts available for transplantation by including individual's hearts that experience circulatory death.

Primary graft dysfunction after heart transplantation: Outcomes and resource utilization.

BACKGROUND: A unified definition of primary graft dysfunction (PGD) after heart transplantation was adopted in 2014, with moderate and severe PGD defined as a need for mechanical circulatory support. While risk factors for PGD are well identified, outcomes and resource utilization have not been well-studied. We examined the resource utilization and associated costs with PGD. METHODS: All adult heart transplantations (2001-2016) from a statewide Society of Thoracic Surgery database were analyzed by dividing them into two groups-with PGD (requiring mechanical circulatory support) and without PGD. RESULTS: Of the 718 heart transplants, 110 (15.3%) patients developed PGD. Prevalence of PGD for the study duration ranged from 3.7% to 22.7% with no significant trend. The most frequently used mechanical circulatory support device was intra-aortic balloon pump (88%), followed by extracorporeal membrane oxygenation (17%), and catheter-based circulatory support devices (3%). There were no significant differences in demographics or preoperative variables between the two groups. Resource utilization such as total intensive care unit hours, ventilation hours, reoperation for bleeding, blood product transfusions, and length of stay were significantly higher in the PGD group. Postoperative complications were also higher in PGD group including operative mortality (31.8% vs 3.8%, P < .0001). The median cost of heart transplantation was significantly higher in the PGD group $229 482 ($126 044-$388 889) vs $101 788 ($72 638-$181 180) P < .0001. CONCLUSION: Primary graft dysfunction following heart transplantation developed in 15% of patients. Patients with PGD had significantly higher complications, resource utilization, and mortality. Preventive measures to address the development of PGD would reduce resource utilization and improve outcomes.

Exercise Capacity in Patients with the Total Artificial Heart.

There is a dearth of information regarding the functional abilities of patients with the total artificial heart (TAH). Increased utilization of the TAH and patient discharge to home with the portable unit necessitates a shift in focus to quality of life, which includes quantifying and ultimately optimizing functional capacity. To date, only single-patient case studies have described the exercise response of the TAH patient. Fourteen patients with the TAH underwent cardiopulmonary exercise testing with concurrent analysis of TAH device function. All device settings remained fixed during testing. Peak oxygen consumption (VO2; 0.872 L/min [interquartile range (IQR) = 0.828-1.100 L/min]), percent predicted peak VO2 (36% [IQR = 32-42%]), and ventilatory anaerobic threshold (0.695 L/min [IQR = 0.542-0.845 L/min]) were markedly reduced in the TAH compared with predicted normal values. Determinants of VO2 using device-generated hemodynamics revealed a blunted cardiac output (+9% increase) and exaggerated oxygen extraction with exercise. Peak VO2 strongly correlated with resting (R = +0.548, p = 0.045), ventilatory anaerobic threshold (R = +0.780, p = 0.001), and peak exercise cardiac output (R = +0.672, p = 0.008). Patients with the TAH have significantly impaired exercise performance. The limitations to cardiopulmonary exercise testing performance appear to be related to limited ability of the pump to modulate output for activity and reduced oxygen carrying capacity.

Severe tricuspid regurgitation due to interactions with right ventricular permanent pacemaker or defibrillator leads.

Although thought to be a rare event, permanent pacemakers and implantable cardioverter-defibrillators with right ventricular intracardiac leads have the potential to induce tricuspid valve dysfunction. Adverse lead-valve interactions can take place through a variety of mechanisms including damage at the time of implantation, leaflet pinning, or long-term fibrosis encapsulating the leaflet tissue. Clinical manifestations can display a wide range of severity, as well as a highly variable time span between implantation and hemodynamic deterioration. This review aims to describe the potential pathophysiologic effects of intracardiac device leads on the tricuspid valve, with a focus on ideal diagnostic strategies and treatment options once lead-induced valvular dysfunction is suspected.

Interagency registry for mechanically assisted circulatory support report on the total artificial heart.

BACKGROUND: We sought to better understand the patient population who receive a temporary total artificial heart (TAH) as bridge to transplant or as bridge to decision by evaluating data from the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) database. METHODS: We examined data related to survival, adverse events, and competing outcomes from patients who received TAHs between June 2006 and April 2017 and used hazard function analysis to explore risk factors for mortality. RESULTS: Data from 450 patients (87% men; mean age, 50 years) were available in the INTERMACS database. The 2 most common diagnoses were dilated cardiomyopathy (50%) and ischemic cardiomyopathy (20%). Risk factors for right heart failure were present in 82% of patients. Most patients were INTERMACS Profile 1 (43%) or 2 (37%) at implantation. There were 266 patients who eventually underwent transplantation, and 162 died. Overall 3-, 6-, and 12-month actuarial survival rates were 73%, 62%, and 53%, respectively. Risk factors for death included older age (p = 0.001), need for pre-implantation dialysis (p = 0.006), higher creatinine (p = 0.008) and lower albumin (p < 0.001) levels, and implantation at a low-volume center (≤10 TAHs; p < 0.001). Competing-outcomes analysis showed 71% of patients in high-volume centers were alive on the device or had undergone transplantation at 12 months after TAH implantation vs 57% in low-volume centers (p = 0.003). CONCLUSIONS: Patients receiving TAHs have rapidly declining cardiac function and require prompt intervention. Experienced centers have better outcomes, likely related to patient selection, timing of implantation, patient care, and device management. Organized transfer of knowledge to low-volume centers could improve outcomes.

Measurement of Blood Loss in Cardiac Surgery: Still Too Much.

BACKGROUND: Cardiac surgery is associated with a significant decrease in hematocrit. It is unclear whether that occurs from hemodilution, loss of red cells, or both. Hematocrit is a major determinant of transfusion decisions although transfusion is associated with increased morbidity and mortality. Physicians must determine whether this anemia is the result of hemodilution or red blood cell loss as the former would be treated with packed red blood cell transfusions and the latter by diuresis. We hypothesize that the decrease in hematocrit observed in cardiac surgery is due to hemodilution. METHODS: Blood volume (BV), plasma volume (PV), and red blood cell volume (RBCV) were measured in 54 patients undergoing coronary artery bypass graft surgery, valve surgery, or coronary artery bypass graft/valve surgery. Measurements were made preoperatively, immediately postoperatively, and 2 hours after surgery utilizing a dilution tracer method and hematocrit measurements. RESULTS: Preoperative average BV was 6,094 mL (SD 1,904 mL), RBCV was 2,024 mL (SD 720 mL), and PV was 4,070 mL (SD 1,339 mL). Postoperative average BV was 4,834 mL (SD 1,432 mL), RBCV 1,226 mL (SD 527 mL), and PV 3,607 mL (SD 993 mL). Blood volume decreased 18% (p < 0.0001), RBCV decreased 38% (p < 0.001), and PV decreased 8% (p < 0.012). There were no significant changes between postoperative values and those 2 hours later in the cardiac surgery intensive care unit. CONCLUSIONS: Decreases in hematocrit observed in cardiac surgery patients are due to significant red blood cell losses and not to hemodilution. Red blood cell losses averaged 38%. Plasma volume also decreased.

Determination of Optimal Coronary Flow for the Preservation of "Donation after Circulatory Death" in Murine Heart Model.

Donation after circulatory death donors (DCD) have the potential to increase the number of heart transplants. The DCD hearts undergo an extended period of warm ischemia, which mandates the use of machine perfusion preservation if they are to be successfully recovered for transplantation. Because the minimum coronary artery flow needed to meet the basal oxygen demand (DCRIT) of a DCD heart during machine perfusion preservation is critical and yet unknown, we studied this in a DCD rat heart model. Adult male rats were anesthetized, intubated, heparinized, and paralyzed with vecuronium. The DCD hearts (n = 9) were recovered 30 minutes after circulatory death whereas non-DCD control hearts (n = 12) were recovered without circulatory death. Hearts were perfused through the aorta with an oxygenated Belzer Modified Machine Perfusion Solution (A3-Bridge to Life Ltd. Columbia, SC) at 15°C or 22°C starting at a flow index of 300 ml/100 g/min and decreasing by 40 ml/100 g/min every 10 minutes. Inflow (aortic) and outflow (inferior vena cava) perfusate samples were collected serially to assess the myocardial oxygen consumption index (MVO2) and O2 extraction ratio. The DCRIT is the minimum coronary flow below which the MVO2 becomes flow dependent. The MVO2, DCRIT, and oxygen extraction ratios were higher in DCD hearts compared with control hearts. The DCRIT for DCD hearts was achieved only at 15°C and was significantly higher (131.6 ± 7 ml/100 g/min) compared with control hearts (107.7 ± 8.4 ml/100 gm/min). The DCD hearts sustain warm ischemic damage and manifest higher metabolic needs during machine perfusion. Establishing adequate coronary perfusion is critical to preserving organ function for potential heart transplantation.

Left ventricular assist devices versus medical management in ambulatory heart failure patients: An analysis of INTERMACS Profiles 4 and 5 to 7 from the ROADMAP study.

BACKGROUND: The ROADMAP study showed survival with improved functional status was better with left ventricular assist device (LVAD) therapy compared with optimal medical management (OMM) in ambulatory, non-inotrope-dependent (INTERMACS [IM] Profile 4 to 7) patients. To study more balanced cohorts and better define which patients may benefit from implantation of an LVAD, we re-evaluated the patients enrolled in ROADMAP when stratified by INTERMACS profile (Profile 4 and Profiles 5 to 7). METHODS: The primary end-point (survival on original therapy with improvement in 6-minute walk distance ≥75 meters at 1 year), actuarial survival, adverse events (AEs) and health-related quality of life (HRQoL) were evaluated. RESULTS: For INTERMACS Profile 4 (IM4), more LVAD patients met the primary end-point compared with OMM patients (40% vs 15%; odds ratio = 3.9 [1.2 to 12.7], p = 0.024), but there was no statistically significant difference for INTERMACS Profiles IM 5 to 7 (IM5-7). Event-free survival on original therapy at 2 years was greater for LVAD than for OMM patients in both IM4 (67% vs 28%; p < 0.001) and IM5-7 (76% vs 49%; p = 0.025) profile groups. Composite end-points of survival on original therapy with improved HRQoL or depression were better with LVAD than OMM in IM4, but not IM5-7. AEs trended higher in LVAD compared with OMM patients in both profile groups. Rehospitalization rates for LVAD vs OMM were similar between treatment arms in IM4 (82% vs 86%; p = 0.780), but were higher for LVAD in IM5-7 (93% vs 71%; p = 0.016). CONCLUSIONS: LVAD patients in IM4, but not IM5-7, are more likely to meet the primary end-point and have improvements in HRQoL and depression compared with OMM, even with AEs generally being more frequent. LVAD therapy with current technology may be beneficial in select IM4 patients, but can be deferred for most IM5-7 patients, who should be followed closely due to the high frequency of treatment failures.

Metabolomics and Precision Medicine in Trauma: The State of the Field.

Trauma is a major problem in the United States. Mortality from trauma is the number one cause of death under the age of 45 in the United States and is the third leading cause of death for all age groups. There are approximately 200,000 deaths per year due to trauma in the United States at a cost of over $671 billion in combined healthcare costs and lost productivity. Unsurprisingly, trauma accounts for approximately 30% of all life-years lost in the United States. Due to immense development of trauma systems, a large majority of trauma patients survive the injury, but then go on to die from complications arising from the injury. These complications are marked by early and significant metabolic changes accompanied by inflammatory responses that lead to progressive organ failure and, ultimately, death. Early resuscitative and surgical interventions followed by close monitoring to identify and rescue treatment failures are key to successful outcomes. Currently, the adequacy of resuscitation is measured using vital signs, noninvasive methods such as bedside echocardiography or stroke volume variation, and other laboratory endpoints of resuscitation, such as lactate and base deficit. However, these methods may be too crude to understand cellular and subcellular changes that may be occurring in trauma patients. Better diagnostic and therapeutic markers are needed to assess the adequacy of interventions and monitor responses at a cellular and subcellular level and inform clinical decision-making before complications are clinically apparent. The developing field of metabolomics holds great promise in the identification and application of biochemical markers toward the clinical decision-making process.