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Purpose of review Timely referral of eligible candidates for consideration of advanced therapies, such as a heart transplantation or mechanical circulatory support is essential. The characteristics of heart transplantation candidates have changed significantly over the years, leading to a more complex evaluation process. The present review summarizes recent advances in the evaluation process for heart transplantation eligibility. Recent findings The heart transplantation allocation policy was recently reviewed in the USA in an effort to reduce waitlist mortality and to ensure fair geographic allocation of organs to the sickest patients. Moreover, patients with chronic infectious diseases, as well as malignancies, are being currently considered acceptable candidates for transplantation. Listing practices for heart transplantation vary between programmes, with a greater willingness to consider high-risk candidates at higher-volume centres. Summary The ultimate decision to place high-risk candidates on the heart transplantation waitlist should be based on a combination of quantitative and qualitative data analysis informed by clinical judgement, and the chronic shortage of organ donors makes this process an important ethical concern for any society. Future guidelines should discuss approaches to achieve fair organ allocation while preserving improved outcomes after transplantation.

Background: The MOMENTUM 3 study (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) has demonstrated that the HeartMate 3 (HM3) pump is associated with reduced strokes compared with the HeartMate II (HMII) device. We now perform a comprehensive analysis of stroke events to evaluate their longitudinal occurrence, clinical correlates, patterns, and impact on outcome across the 2-year duration of support. Methods: MOMENTUM 3 is a randomized controlled trial of the HM3 centrifugal-flow pump versus the HMII axial-flow pump in patients with advanced heart failure, regardless of the intended goal of support (bridge to transplantation or destination therapy). Baseline and postimplantation clinical correlates of stroke events were assessed with multivariable analyses. Longitudinal patterns, including device association, type of stroke (hemorrhagic versus ischemic), changing severity of impairment assessed with the modified Rankin Scale (disabling [modified Rankin Scale score >3] versus nondisabling [modified Rankin Scale score ≤3]) over time, and association with outcome, were determined. Results: In 361 patients with the intended implant (189 HM3 and 172 HMII), 65 strokes (40 ischemic strokes and 25 hemorrhagic strokes) occurred in 52 patients at a median of 131 (range, 1–733) days. No difference in stroke rate was noted between 0 and 180 days of follow-up between devices. However, stroke incidence in the long-term period (181–730 days after left ventricular assist device) was 3.3 times lower for the HM3 group (HM3: 0.04 versus HMII: 0.13 events per patient-year; odds ratio, 0.23; 95% CI, 0.08–0.63; P =0.01). Treatment with the HM3 pump was the only independent predictor of lower stroke events. We found no direct association of blood pressure or antithrombotic regimens with observed stroke rates. A stroke event significantly lowered 2-year postimplantation survival regardless of subtype or initial severity of neurological impairment compared with patients without a stroke (43±12% for hemorrhagic stroke, 57±9% for ischemic stroke, 51±11% for disabling, and 51±11% for nondisabling compared with 85±2% 2-year survival for patients without stroke). Conclusions: The HM3 pump is associated with a marked reduction in stroke rates compared with the HMII device, with benefits observed in the long-term period (>6 months). The occurrence of stroke of any type (hemorrhagic and ischemic) or of any functional severity (disabling and nondisabling) is predictive of a poor 2-year clinical outcome. Clinical Trial Registration: URL: https://www.clinicaltrials.gov/ . Unique identifier: NCT02224755.

Introduction: The volume of solid organ transplantation in the US has increased in recent years. Few data are available characterizing thoracic transplantation patterns and outcomes by citizenship status. Methods: Citizenship at the time of transplantation was characterized among thoracic organ transplantation recipients in the US between 2013 and 2018 using United Network for Organ Sharing data. The non-US citizen group included non-US citizen/US residents, non-US citizen/non-US residents who travelled to the US for transplantation, and non-US citizen/non-US residents who travelled to the US for reasons other than transplantation. Cox regression models were constructed to examine the association between citizenship status and death or graft failure, accounting for age, sex, race, and payment method. Results: Among 31,174 thoracic organ transplantations, number of non-US citizen thoracic organ recipients increased from 90 in 2013 to 221 in 2018 (a 146% increase). Proportion of non-US citizen recipients (of all recipients) similarly increased from 2.0% in 2013 to 3.7% in 2018 (Figure 1a). Non-US citizens were, on average, younger than US citizens (46±19 vs 51±19 years, p Conclusions: Between 2013 and 2018, there was a modest increase in non-US citizen recipients of thoracic organ transplantation. Non-US citizens have similar risk-adjusted patient and graft survival when undergoing thoracic organ transplantation compared with US citizens.

Background: The MOMENTUM 3 trial compares the centrifugal HeartMate 3 (HM3) with the axial HeartMate II (HMII) continuous-flow left ventricular assist system in patients with advanced heart failure, irrespective of the intended goal of therapy. The trial’s 2-year clinical outcome (n=366) demonstrated superiority of the HM3 for the primary end point (survival free of a disabling stroke or reoperation to replace or remove a malfunctioning pump). This analysis evaluates health resource use and cost implications of the observed differences between the 2 devices while patients were enrolled in the trial. Methods: We analyzed all hospitalizations and their associated costs occurring after discharge from the implant hospitalization until censoring (study withdrawal, heart transplantation, and pump exchange with a nonstudy device or death). Each adjudicated episode of hospital-based care was used to calculate costs (device-attributable and non–device-attributable event costs), estimated by using trial data and payer administrative claims databases. Cost savings stratified by subgroups (study outcome [transplant, death, or ongoing on device], intended goal of therapy, type of insurance, or sex) were also assessed. Results: In 366 randomly assigned patients, 361 comprised the as-treated group (189 in the HM3 group and 172 in the HMII group), of whom 337 (177 in the HM3 group and 160 in the HMII group) were successfully discharged following implantation. The HM3 arm experienced fewer total hospitalizations per patient-year (HM3: 2.1±0.2 versus HMII: 2.7±0.2; P =0.015) and 8.3 fewer hospital days per patient-year on average (HM3: 17.1 days versus HMII: 25.5 days; P =0.003). These differences were driven by patients hospitalized for suspected pump thrombosis (HM3: 0.6% versus HMII: 12.5%; P P =0.002). Controlled for time spent in the study (average cumulative cost per patient-year), postdischarge HM3 arm costs were 51% lower than with the HMII (HM3: $37 685±4251 versus HMII: $76 599±11 889, P Conclusions: In this 2-year outcome economic analysis of the MOMENTUM 3 trial, the HM3 demonstrated a reduction in rehospitalizations, hospital days spent during rehospitalizations, and a significant cost savings following discharge in comparison with the HMII left ventricular assist system, irrespective of the intended goal of therapy. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02224755.

Background: Center differences in short-term survival after heart transplant (HT) are known. We sought to compare long-term graft survival (freedom from death or retransplantation) at currently active United States HT centers stratified by performance for short-term survival. Methods: We used the Organ Procurement and Transplant Network database to identify subjects ≥18 years old who received primary HT during 2000 to 2014 at US centers active during 2013 and 2014. Follow-up was available until March 2016. Center case-mix was assessed by computing expected 90-day mortality and short-term performance by 90-day standardized mortality ratio (SMR; observed/expected mortality). Centers were stratified by case-mix as transplanting low-, intermediate-, and high-risk patients and by short-term performance as SMR quintiles. Center-level differences in long-term graft survival were assessed by risk-adjusted, mixed-effects Weibull survival models with center as a random effect. Results: We analyzed 25 467 HT recipients at 96 centers. Those receiving HT at centers with superior (lower) 90-day SMR had longer graft survival ( P for trend P for trend P P Conclusions: HT recipients at centers with superior short-term outcomes have longer graft survival on long-term follow-up. Allocating resources to improve patient care processes and transplant expertise at high-SMR centers may improve short-term and overall survival after HT.

Background: A cohort of heart failure (HF) patients receiving left ventricular assist devices (LVADs) has decoupling of their diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. However, the clinical implications of this decoupling remain unclear. Methods and Results: In this prospective study, patients with LVADs underwent routine invasive hemodynamic ramp testing with right heart catheterization, during which LVAD speeds were adjusted. Inappropriate decoupling was defined as a >5 mm Hg difference between diastolic pulmonary artery pressure and pulmonary capillary wedge pressure. The primary outcomes of survival and heart failure readmission rates after ramp testing were assessed. Among 63 LVAD patients (60±12 years old and 25 female [40%]), 27 patients (43%) had inappropriate decoupling at their baseline speed. After adjustment of their rotation speed during ramp testing, 30 patients (48%) had inappropriate decoupling. Uni/multivariable Cox analyses demonstrated that decoupling was the only significant predictor for the composite end point of death and heart failure readmission during the 1 year following the ramp study (total of 18 events; hazards ratio, 1.09; 95% confidence interval, 1.04–1.24; P P =0.035). Conclusions: The presence of inappropriate decoupling was associated with worse outcomes in patients with LVADs. Prospective, large-scale multicenter studies to validate the result are warranted.

The development of current mechanical circulatory support (MCS) systems began in the 1960s as an effort to provide a therapeutic option for patients with refractory advanced heart failure.1 Today, MCS represents a viable alternative to cardiac transplantation for the overwhelming majority of patients in whom age, comorbidities, or the profound shortage of donors makes transplantation infeasible. Response by Owens and Jessup on p 3087 Painstaking work on the technique of orthotopic cardiac transplantation, coupled with advances in the knowledge of immunology, resulted in the improvements in survival and quality of life that make cardiac transplantation the treatment of choice for individuals with advanced heart failure. MCS has only recently become accepted for widespread clinical use.2 Early MCS designs were based on the assumption that maintaining pulsatility of flow was a physiological necessity. These bulky devices were of limited durability and resulted in a great deal of morbidity in the form of hematologic, neurological, and infectious complications.3 Current (second- and third-generation) devices deliver continuous flow (either axial [HeartMate II] or centrifugal [Heartware HVAD]) and have far fewer moving parts (only a rotor); as a result, they are smaller, quieter, and far more durable (estimated to last ≥10 years compared with 18 months) than the early pulsatile systems.4 Although no longer in common use, early pulsatile-flow left ventricular assist devices (LVADs) provided the first proof of principle that MCS can extend life of well-selected patients with advanced heart failure refractory to traditional optimal medical therapy. The development of continuous-flow devices has made MCS a practical clinical tool, and outcomes with the newer devices provide a convincing rationale for LVADs as standard of care in well-selected patients with refractory heart failure in whom transplantation is not an option. ### Proof of Principle Recognition that LVADs intended as a bridge to cardiac transplantation delivered …

B-type natriuretic peptide (BNP) levels provide diagnostic and prognostic information in heart failure. This study determined the frequency of BNP assessment and analyzed demographic characteristics, clinical variables and the utilization of guideline-recommended heart failure therapies by BNP level in outpatients with reduced left ventricular ejection fraction (LVEF).The IMPROVE HF registry (The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting) is a prospective cohort study of patients at least 18 years of age with a LVEF 35% or less and chronic heart failure or previous myocardial infarction (MI) presenting to cardiology and multispecialty practices. The medical records of 15,381 patients were reviewed. BNP was measured in 4213 (27.4%) patients and the median plasma BNP level was 384 pg/ml (interquartile range 158-877 pg/ml). Patients were stratified by plasma BNP measurements into the following tertiles: 219 pg/ml or less, more than 219 to 649 pg/ml, and more than 649 pg/ml. Jugular venous distension, pedal edema, rales and systolic murmur on physical examination and elevated renal function parameters were associated with higher BNP levels. BNP assessment and elevated BNP levels were not associated with greater use of any of the quality of care measures. However, patients with a BNP in the top tertile were less likely to be treated with angiotensin-converting enzyme inhibitors/angiotensin receptor blockers or aldosterone antagonists compared with patients with a BNP in the bottom tertile.Among practices participating in IMPROVE HF, BNP was not measured in most outpatients with reduced LVEF and chronic heart failure or previous MI. BNP assessment or the BNP level in patients with recorded measurements, with few exceptions, did not impact the utilization of guideline-recommended therapies.

Background— A treatment gap exists between heart failure (HF) guidelines and the clinical care of patients. The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting (IMPROVE HF) prospectively tested a multidimensional practice-specific performance improvement intervention on the use of guideline-recommended therapies for HF in outpatient cardiology practices. Methods and Results— Performance data were collected in a random sample of HF patients from 167 US outpatient cardiology practices at baseline, longitudinally after intervention at 12 and 24 months, and in single-point-in-time patient cohorts at 6 and 18 months. Participants included 34 810 patients with reduced left ventricular ejection fraction (≤35%) and chronic HF or previous myocardial infarction. To quantify guideline adherence, 7 quality measures were assessed. Interventions included clinical decision support tools, structured improvement strategies, and chart audits with feedback. The performance improvement intervention resulted in significant improvements in 5 of 7 quality measures at the 24-month assessment compared with baseline: β-blocker (92.2% versus 86.0%, +6.2%), aldosterone antagonist (60.3% versus 34.5%, +25.1%), cardiac resynchronization therapy (66.3% versus 37.2%, +29.9%), implantable cardioverter-defibrillator (77.5% versus 50.1%, +27.4%), and HF education (72.1% versus 59.5%, +12.6%) (each P Conclusions— The Registry to Improve the Use of Evidence-Based Heart Failure Therapies in the Outpatient Setting, a defined and scalable practice-specific performance improvement intervention, was associated with substantial improvements in the use of guideline-recommended therapies in eligible patients with HF in outpatient cardiology practices. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00303979.

Geometric mitral regurgitation is a phenomenon encountered by an otherwise anatomically normal mitral valve in the setting of advanced adverse left ventricular remodeling that alters the alignment characteristics of the mitral valve apparatus leading to functional production of a leaking valve. In this review, we discuss contemporary directions in the knowledge base for managing geometric mitral regurgitation.Much progress has been encountered in describing the types of geometric mitral regurgitation (nonischemic and ischemic origins), standardization of echocardiographic techniques to allow for a common language in ascertaining the severity of mitral regurgitation, knowledge on dynamic mitral regurgitation during exercise, effectiveness of therapy and appropriate use and timing of surgical repair.Geometric mitral regurgitation develops in tandem with progressive ischemic or nonischemic cardiomyopathy and can improve with antiremodeling pharmacological and device-based therapy. Surgical therapy can be accomplished at experienced centers with low morbidity and mortality, and may improve symptoms and enhance pump function. Whether such therapy saves lives remains uncertain. New percutaneous approaches to tackle geometric mitral regurgitation are developing, and early data is encouraging but remains experimental.

Background— Prior investigations suggest that superimposing continuous flow on aortic flow (continuous aortic flow augmentation) produces vasodilation, cardiac unloading, and improved cardiac performance. Methods and Results— We compared percutaneous continuous aortic flow augmentation (flow ≤1.5 L/min for up to 96 hours) plus medical therapy versus medical therapy alone by randomizing 168 patients (device, n=109; control, n=59) hospitalized with heart failure, reduced left ventricular ejection fraction and cardiac index, elevated pulmonary capillary wedge pressure, and renal impairment or substantial diuretic requirement despite intravenous inotropes/vasodilators. The primary composite efficacy end point included pulmonary capillary wedge pressure (72 to 96 hours) and days alive out of hospital off mechanical support over 35 days. The population’s illness severity posed unique challenges. Enrollment ended early because of an inability to demonstrate significant benefit on the primary composite end point (device, 17.4%; control, 13.6%; P =0.45) in the face of excess device group bleeding. Pulmonary capillary wedge pressure decreased from 28.8±6.3 mm Hg (mean±SD) to 24.9±7.2 mm Hg (average, 72 to 96 hours) and 28.9±7.1 to 26.5±6.2 mm Hg in the device and control groups, respectively (between-group P =0.074). Cardiac index progressively increased in the device (2.05±0.53 to 2.44±0.52 L · min −1 · m −2 ) but not the control (between-group P P =0.10). Through 65 days, device-to-control hazard ratios were as follows: all-cause mortality, 1.05 (95% confidence interval, 0.60 to 1.82); death or heart failure hospitalization, 0.87 (95% confidence interval, 0.57 to 1.33); and heart failure hospitalization, 0.66 (95% confidence interval, 0.38 to 1.13). Major bleeds occurred in 16.5% in the device (7.3% treatment related) and 5.1% in the control ( P =0.05) group. Conclusions— Continuous aortic flow augmentation improved cardiac performance, improving cardiac index and pulmonary capillary wedge pressure, but statistical significance for the primary efficacy end point was not attained. Hemodynamic and clinical observations provide direction toward additional studies to further investigate the clinical effects of this treatment.

Background— Few data exist regarding contemporary care patterns for heart failure (HF) in the outpatient setting. IMPROVE HF is a prospective cohort study designed to characterize current management of patients with chronic HF and ejection fraction ≤35% in a national registry of 167 US outpatient cardiology practices. Methods and Results— Baseline patient characteristics and data on care of 15381 patients with diagnosed HF or prior myocardial infarction and left ventricular dysfunction were collected by chart abstraction. To quantify use of therapies, 7 individual metrics (use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, β-blocker, aldosterone antagonist, anticoagulation, implantable cardioverter defibrillator, cardiac resynchronization therapy, and HF education) and composite metrics were assessed. Care metrics include only patients documented to be eligible and without contraindications or intolerance. Among practices, 69% were nonteaching. Patients were 71% male, with a median age of 70 years, and a median ejection fraction of 25%. Use of angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (80%) and β-blocker (86%) was relatively high in eligible patients in the outpatient cardiology setting; other metrics, such as aldosterone antagonist (36%), device therapy (implantable cardioverter defibrillator/cardiac resynchronization therapy with defibrillator, 51%; cardiac resynchronization therapy, 39%), and education (61%), showed lower rates of use. A median 27% of patients received all HF therapies for which they were potentially eligible on the basis of chart documentation. Use of guideline-recommended therapies by practices varied widely. Conclusions— These data are among the first to assess treatment in the outpatient setting since the release of the latest national HF guidelines and to demonstrate substantial variation among cardiology practices in the documented therapies provided to HF patients.

Although the age-adjusted mortality from heart disease has declined in the United States, cardiovascular disease remains the No. 1 cause of death.1,2 Patients with cardiac disease generally die of one of 2 causes: sudden, unexpected cardiac death or progressive heart failure. Chronic heart failure (CHF) has become an epidemic in the United States. Implantable cardioverter-defibrillator (ICD) therapy has had a major impact on the treatment of heart failure in the United States. The ICD has been shown to decrease mortality relative to the best medical therapy in patients who have survived an episode of sustained ventricular tachycardia (VT) or ventricular fibrillation (VF).3 Unfortunately, only a small minority of patients who experience an out-of-hospital cardiac arrest in the United States are successfully resuscitated.4 Thus, ICD therapy has been applied for the primary prevention of sudden death in patients at high risk of cardiac arrest. Once thought to be a “bystander” curiosity in the progression of heart failure, electrical-conduction disturbances are now recognized to be important causes of left ventricular (LV) dysfunction. Cardiac resynchronization therapy (CRT) can restore more-normal electrical contraction and, when combined with defibrillation (CRTD), can have a major impact on the mortality and morbidity of heart failure. Although there remain many limitations and challenges to the appropriate application of ICDs or CRTD, there is no question that device therapy has had a major impact on the management of patients with LV dysfunction. The ICD was developed in the 1970s as a device to detect and automatically terminate ventricular tachyarrhythmias.5,6 Early ICDs were large devices that required a thoracotomy to implant. Improvements in batteries, capacitors, and microprocessors7 have resulted in the rapid evolution of ICD technology. Current-generation ICDs are small enough to be easily implanted in the pectoral region and can perform a variety of …

Cardiac resynchronization therapy (CRT) is a relatively new therapy for patients with symptomatic heart failure resulting from systolic dysfunction. CRT is achieved by simultaneously pacing both the left and right ventricles. Biventricular pacing resynchronizes the timing of global left ventricular depolarization and improves mechanical contractility and mitral regurgitation. Published clinical trials have demonstrated that CRT results in improved clinical status and lower mortality rate when selected patients with systolic ventricular dysfunction and heart failure are treated with CRT. This advisory identifies appropriate candidates for CRT on the basis of the inclusion criteria and results from the published clinical trials.

Congestive heart failure (CHF) is a major cardiovascular disorder that is increasing in incidence, prevalence, and lethality. The prognostic significance of cardiac troponin levels among symptomatic and asymptomatic CHF has attracted recent interest. We sought to assess the significance of cardiac troponins in heart failure. These cardiac markers are associated with decreased left ventricular ejection fraction and poor prognosis in patients with CHF and are related to the severity of heart failure. The mechanism for the release of these markers seems to be from ventricular remodeling, ongoing myocyte degeneration, the presence of coronary artery disease, and reduced coronary reserve. In addition to B-type (brain) natriuretic peptide (BNP), cardiac troponin levels measured in patients admitted to the hospital could help risk-stratify patients and manage them effectively. BNP and cardiac troponins are easy to measure and can be repeated many times to follow patients, without interobserver variability. Theoretically, BNP is a marker of heart failure status and cardiac troponin is a marker of myocyte injury. The first therapeutic goal could be relief of circulatory congestion and lowering of BNP. The second goal could be attenuation of myocyte injury and lowering of cardiac troponins. Measuring and monitoring the levels of both could be highly effective means to reliably stratify the patients into low-, intermediate-, and high-risk groups for cardiac events and progression of heart failure. Furthermore, large-scale trials are necessary to establish them as noninvasive monitoring markers of heart failure and effectiveness of treatment.

The 20th annual meeting of the Heart Failure Society of America (HFSA) (September 17–20, 2016), held in Orlando, Florida, assembled multidisciplinary teams of clinicians and scientists for a thrilling journey of high-quality patient-centered care, an emerging theme of implementation science and trial interpretation. Two trials of the vasopressin antagonist Tolvaptan in the setting of hospitalized heart failure (HF), and 2 separate applications of palliative care in advanced stage HF, debuted at the meeting. The aquaretic Tolvaptan was studied in the TACTICS (Targeting Acute Congestion With Tolvaptan in Congestive HF Study) and SECRET of CHF (Study to Evaluate Challenging Responses to Therapy in …

See related article, p 2702 . In the past 50 years, we have learnt to transition mechanical circulatory support devices, such as durable left ventricular assist systems (LVAS), from crisis intervention life-saving devices to the contemporary era of using such therapy in prolonging meaningful life in patients with advanced heart failure.1 Despite generational shifts in engineering of such devices, from large pulsatile mechanisms to smaller continuous flow devices, the complications related to neurological adverse effects have not improved substantially.2,3 Hemorrhagic and ischemic strokes continue to occur, with a frequency greater than that observed in patients with advanced heart failure.2 This complication has limited the expansion of such devices to patients with less severe stages of illness, and the quest to understand these devastating events and to prevent them is ongoing. Most studies of neurological complications with LVAS have found a strong correlation between elevated mean arterial blood pressure, anticoagulation levels, and systemic infection.3–5 Ischemic strokes can occur because of thrombi that pass from the heart through the device and into the brain or could develop in unique locations, such as the aortic surface of the valves within the sinus of Valsalva, the carotid bulb, and in some cases …

Background The frequency and outcome of hepatitis C virus (HCV) infection in recipients of hearts from HCV-infected donors remains poorly characterized. Methods Between 1991 and 1999, 10 anti-HCV-negative patients received hearts from donors who were anti-HCV and HCV RNA-positive. Each recipient was tested for anti-HCV and HCV RNA and serially evaluated for liver dysfunction. Recipient records were reviewed for cumulative steroid boluses in the first posttransplant year and other components of the immune suppression regimen. We analyzed recipient outcome in relation to the virologic status of the donor, including the level of HCV RNA and genotype and the type of antirejection therapy. Results All 10 recipients became HCV RNA positive. Donor-recipient pairs expressed identical genotypes in each instance. Six of nine evaluable recipients developed biochemical evidence of hepatitis. Recipients with genotype 1 (1a, 1b) accounted for five of the six cases, and all patients with genotype 1 developed hepatitis. Severe liver injury occurred in two patients. Two deaths occurred, both of which were genotype 1 patients who had been given multiple boluses of corticosteroids in the first posttransplant year. No definite relationship between viral load in the donor and recipient outcome was found. Conclusion Transmission of HCV infection from cardiac donors who are viremic at the time of organ donation occurs with high frequency and can cause severe hepatitis. Hearts from infected patients should probably be restricted to those recipients who already have evidence for hepatitis C or are in need of emergent transplantation.

The detection of anti-human leukocyte antigen (HLA) donor-specific antibodies has been associated with a variety of clinical syndromes that determine short-term and long-term outcomes of cardiac transplant recipients, including an increased incidence of early and more severe allograft rejection and cardiac allograft vasculopathy. Recent surveys indicate marked heterogeneity in clinical protocols for detection and management of sensitization in heart transplantation. The commonly performed complement-dependent cytotoxicity assay is insensitive compared with newer methods such as flow cytometry for antibody screening. The imperative exists to create strategies that can decrease the level of sensitization and increase the likelihood for a negative crossmatch. In this effort, several strategies have been suggested, including administration of intravenous immunoglobulin, apheresis, and combination therapies using potent immunosuppression, particularly with cyclophosphamide. The future of managing allosensitization may be in induction of a chimeric state to allow graft tolerance.

OBJECTIVE To review the outcome of cholecystectomy after heart transplant. SUMMARY BACKGROUND DATA The optimal timing for gallbladder surgery in heart transplant patients is controversial. METHODS Between April 1985 and October 2000, 518 cardiac transplants were performed at Ochsner Foundation Hospital. Data gathered included ultrasound reports, cholecystectomy operative reports, gallbladder pathologic reports, complications, and deaths. RESULTS Charts were available for 509 patients (98%), 68 (13%) of whom underwent cholecystectomy before transplantation. Of the 509, 53 (10%) had serial ultrasound examinations and 29 of the 53 (55%) developed gallstones. After transplant, 47 (9%) underwent cholecystectomy. Five cholecystectomies were performed during the immediate postoperative course. Two patients who underwent cholecystectomy had acalculous cholecystitis; one was incidental. Four patients died (one with rejection and three with sepsis). After discharge, 42 cholecystectomies were performed: 16 for biliary colic (no deaths, three patients with complications), 19 for acute cholecystitis (one death, nine patients with complications), 5 for biliary pancreatitis (1 death, 1 patient with complications), and 2 others. CONCLUSIONS The risk of morbidity and mortality from gallstone disease is high in cardiac transplant patients, particularly immediately posttransplant. Posttransplant patients require annual ultrasound examinations to detect the onset of gallstone disease, and this risk is higher than in the general population. Gallstones alone are an indication for cholecystectomy in the cardiac transplant patient. Pretransplant cholecystectomy should be considered in clinically stable patients with gallstones.

Background Black American heart transplant recipients receiving cyclosporine-based primary immunoprophylaxis suffer higher rates of allograft rejection with hemodynamic compromise, infections, and posttransplant coronary artery disease. We examined the hypothesis that a combination of tacrolimus and mycophenolate mofetil resurrects clinical outcome of black Americans to those seen in white heart transplant recipients. Methods. Sixty-three adult primary heart transplant recipients were included in this study. Twenty black American and 21 white patients who received tacrolimus-based primary immunoprophylaxis were enrolled in this prospective, observational parallel cohort investigation. A separate group of 22 black American patients were randomly allocated to receive cyclosporine-microemulsion-based primary prophylaxis and served as the control population for assessing outcomes in the black American group. Adjunctive immunosuppression included mycophenolate mofetil and corticosteroids. The primary end-point was the freedom from allograft rejection requiring treatment at 1 year. Secondary end-points included rejection with hemodynamic compromise, and patient or graft survival. Adverse events evaluated included development of infections requiring hospitalization and nonimmunological outcomes including hyperlipidemia, hypertension, and diabetes mellitus (new onset or worsened). Results. Tacrolimus-treated black American patients had greater freedom from allograft rejection requiring treatment at 1 year than those treated with cyclosporine (64% vs. 37%, P=0.01). No differences were noted between tacrolimus-treated black Americans and whites in the primary end point (64% and 67% respectively, P=nonsignificant [NS]). Tacrolimus-based immunosuppression was associated with better 1-year survival in black Americans compared with cyclosporine (95% vs. 73%, P=0.04), and this end point was similar to that achieved in tacrolimus-treated white heart transplant recipients (95%). No differences in infection rates were noted among either group. Cyclosporine-treated black Americans suffered more hyperlipidemia and worse hypertension than tacrolimus-treated patients. Conclusions. Compared with cyclosporine, an immunosuppressive strategy using tacrolimus in black Americans achieves superior efficacy with regard to allograft rejection, higher allograft survival, and similar safety. Furthermore, tacrolimus-based immunosuppression is similar in immunological efficacy and safety in black Americans and in white heart transplant recipients.

Introduction: Standardized Clinical Assessment and Management Plans (SCAMPs) are a novel tool forthe prospective auditing of clinical outcomes and quality improvement in areas of practice variation. Using the SCAMP methodology to address heart failure (HF) discharges, two sites collaborated to investigate adherence to guideline-recommended achievement of optimal volume status and reasons for deviation in clinical practice. Methods: Consecutive patients hospitalized for chronic HF at a tertiary referral center (Brigham and Women’s Hospital, Boston MA, n=108, 55.3%) and community hospital with a dedicated heart failure program (Lancaster General Hospital, Lancaster PA, n=87, 44.6%) were enrolled in a HF SCAMP which recommended discharge only after complete decongestion (defined by jugular venous pressure Results: There were 195 patients enrolled. The average age at BWH was 64 years compared to 79 year at LGH. Overall, 57 (29%) patients had residual congestion at discharge, 37% of patients at BWH and 20% at LGH (p=0.01). However, the average weight change was -4.3kg at BWH and -3.8Kg at LGH. At BWH, the most common reason for inadequate decongestion was renal dysfunction (34% BWH vs. 6% LGH, p=0.04). At LGH, non-cardiac/chronic edema (“edema resistant”) was the most common reason (44% LGH vs. 17% BWH (p=0.08). Plan for continued diuresis at home was more common at LGH (LGH 19% vs. BWH 0%, p=0.03). At 90 days, 37% of congested patients and 23% of completely decongested patients had been readmitted (p=0.08). Conclusions: Nearly 1 in 3 patients admitted for worsening HF were discharged with residual congestion, which was more common at the tertiary care center and trended with higher readmission rates. The reasons for inadequate decongestion were different between sites.

The concept of ventricular assistance as a bridge to recovery of cardiac function has received a great deal of recent attention because of its enormous potential for offering an alternative mode of therapy for an ever-growing list of patients with end-stage heart disease. Although there are clear rationales for the anatomic, histologic, and biochemical alterations facilitated by ventricular support, there has yet to be large-volume predictable clinical success with this concept. Nonetheless, increased awareness of this possibility has led to the development of protocols for patient evaluation and treatment that will lead to increased future successes. Augmented bridges to recovery, such as with proangiogenic therapy or cell transplantation, may be developed as realistic options. An effort to test these hypotheses with approved devices in the bridge-to-transplant population must be developed for this goal to be realized.

Abstract —Altered sympathetic activity and peripheral vascular function are suspected as a mechanism of the development of arterial hypertension in organ transplantation recipients treated with cyclosporine. We assessed whether cyclosporine might alter peripheral vascular properties or autonomic modulation of the sinus node and the vasculature during rest and standing. We examined 17 orthotopic heart transplantation recipients, 8 solid organ transplantation recipients, 17 patients with essential hypertension, and 42 normotensive control subjects. All except the normotensive control subjects were treated with a long-acting dihydropyridine calcium entry blocker; transplantation recipients also received cyclosporine-based immunosuppression. Radial artery compliance was reduced in patients with essential hypertension and in patients with heart and solid organ transplantation as compared with normotensive control subjects, with this reduction being more marked in heart transplantation recipients. At rest, R-R variance was lowest in heart transplantation recipients, denoting denervation. The spectral profile of both R-R and systolic blood pressure variability as well as the index of baroreflex gain was normal at rest in patients with solid organ transplantation. On standing, both transplantation groups demonstrated reduced responsiveness in markers of autonomic modulation. The decrease in arterial compliance in cyclosporine-induced hypertension seems to imply a degree of ventricular vascular uncoupling more apparent in heart transplantation recipients. These changes are associated with alterations in autonomic modulation that are evidenced by an orthostatic stimulus.

The use of cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Several mechanisms, including endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in nitric oxide, and altered cytosolic calcium translocation, have been proposed to underlie cyclosporine-induced hypertension. In addition, other studies have shown activation of the sympathetic nervous system and the renin-angiotensin system, as well as abnormalities in prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of cyclosporine-induced hypertension consist of elevated peripheral vascular resistance, ventricular vascular uncoupling contributing to left ventricular hypertrophy, and abnormalities in the diastolic function of the allograft. Combined calcium-channel blockers and angiotensin-converting enzyme inhibitors have been used for the treatment of this clinical problem, and they achieve blood pressure control in 65% of patients. Moreover, these agents may also be beneficial in preventing development of cardiac allograft vasculopathy, a long-term nemesis in cardiac transplantation.

Background Several therapies are guideline‐recommended to reduce mortality in patients with heart failure (HF) and reduced left ventricular ejection fraction, but the incremental clinical effectiveness of these therapies has not been well studied. We aimed to evaluate the individual and incremental benefits of guideline‐recommended HF therapies associated with 24‐month survival. Methods and Results We performed a nested case‐control study of HF patients enrolled in IMPROVE HF. Cases were patients who died within 24 months and controls were patients who survived to 24 months, propensity‐matched 1:2 for multiple prognostic variables. Logistic regression was performed, and the attributable mortality risk from incomplete application of each evidence‐based therapy among eligible patients was calculated. A total of 1376 cases and 2752 matched controls were identified. β‐Blocker and cardiac resynchronization therapy were associated with the greatest 24‐month survival benefit (adjusted odds ratio for death 0.42, 95% confidence interval (CI), 0.34–0.52; and 0.44, 95% CI, 0.29–0.67, respectively). Angiotensin‐converting enzyme inhibitors/angiotensin receptor blockers, implantable cardioverter‐defibrillators, anticoagulation for atrial fibrillation, and HF education were also associated with benefit, whereas aldosterone antagonist use was not. Incremental benefits were observed with each successive therapy, plateauing once any 4 to 5 therapies were provided (adjusted odds ratio 0.31, 95% CI, 0.23–0.42 for 5 or more versus 0/1, P Conclusions Individual, with a single exception, and incremental use of guideline‐recommended therapies was associated with survival benefit, with a potential plateau at 4 to 5 therapies. These data provide further rationale to implement guideline‐recommended HF therapies in the absence of contraindications to patients with HF and reduced left ventricular ejection fraction.

Background: Variations between outpatient cardiology practices in adherence to guideline-recommended therapies for heart failure (HF) have previously been described. The effect of performance improvement initiatives on reducing these variations has not been evaluated. Methods: IMPROVE HF is a prospective evaluation of a practice-based, performance improvement intervention implemented at cardiology practices to increase use of evidence-based, guideline-recommended care for eligible outpatients with systolic HF or post-myocardial infarction LVSD. Variations in use of 7 individual and 2 summary care measures were assessed by comparing the 10 th and 90 th percentiles, the inter-decile differences, and variance for each measure at baseline (pre-intervention) and 24 months post-intervention. Results: A total of 15,177 patients followed in 155 of 167 practices were available for analysis. Substantial variations for all care measures were evident at baseline with inter-decile differences ranging from 23.6% for β-blockers to 81.3% for CRT-P/CRT-D. The 24-month evaluation revealed significant improvements in adherence to 6 of 7 specific measures, the composite, and all-or-none care measures. However, large care variations persisted among practices with interdecile differences at 24 months ranging from 16.2% to 75.0%. No measure demonstrated significantly reduced variation at 24 months compared to baseline. Conclusions: Implementation of a practice-based performance improvement initiative resulted in substantial improvement in adherence to guideline-recommended therapies for HF. However, wide variations in provision of evidence-based care persisted among cardiology practices. Additional targeted interventions may be necessary to reduce variations in use of guideline-recommended HF therapies in outpatient cardiology practices.

Case report: A 54-year-old man is referred for dyspnea on exertion. He has a history of type II diabetes and 35 pack-years of smoking. He suffered an anterior myocardial infarction 14 months ago, and on recent echocardiography was found to have an ejection fraction of 25%. Since his myocardial infarction, he has quit smoking and has gained an additional 27 pounds. He admits to a sedentary lifestyle and has recently tried to initiate an exercise program in an effort to lose weight. His current body mass index is 33.4 kg/m2. He denies orthopnea but does have progressive lower-extremity edema. What is the primary cause of his dyspnea? Is it ventilatory or circulatory? Obesity or deconditioning? What is the prognosis for his ischemic cardiomyopathy? What would be the appropriate diagnostic study to obtain these answers? Exercise stress testing is commonly used in clinical practice to evaluate the presence and severity of coronary ischemia. A significant enhancement of clinical information available during exercise can be obtained by concurrent measurement of respiratory gas exchange via use of a metabolic cart. This modality of stress testing has been called cardiopulmonary stress testing (CPX). This article will update the cardiovascular clinician on the utility of CPX in the modern cardiovascular practice. A major function of the cardiovascular system is gas exchange, supplying O2 and other fuels to working muscles, as well as removal of CO2 and other metabolites. The heart, lungs, and pulmonary and systemic circulations form a single circuit for exchange of respiratory gases between the environment and the cells of the body.1,2 Under steady-state conditions, respiratory oxygen uptake (Vo2) and carbon dioxide outflow (Vco2) measured at the mouth are equivalent to oxygen utilization (![Graphic][1] o2) and carbon dioxide production (![Graphic][2] co2) occurring in the … [1]: /embed/inline-graphic-1.gif [2]: /embed/inline-graphic-2.gif

ObjectivesThis study was designed to assess the effects of three-month formal phase II cardiac rehabilitation and exercise training programs on high-sensitivity C-reactive protein (HSCRP) levels in patients with coronary heart disease (CHD).BackgroundHigh-sensitivity C-reactive protein is associated with abdominal adiposity and other CHD risk factors and is a potent independent predictor of CHD events. Although weight reduction and statin therapy reduce HSCRP levels, the independent effects of cardiac rehabilitation programs on HSCRP are not well established.MethodsWe analyzed plasma levels of HSCRP in 277 patients with CHD (235 consecutive patients before and after formal phase II cardiac rehabilitation and exercise training programs and 42 “control” patients who did not attend cardiac rehabilitation). Additionally, we determined the effects of cardiac rehabilitation on HSCRP independent of statin therapy and weight loss.ResultsRehabilitation patients improved significantly in body fat, obesity indices, exercise capacity, and other cardiac risk factors. Mean (5.9 ± 7.7 to 3.8 ± 5.8 mg/l; −36%; p < 0.0001) and median levels of HSCRP (−41%; p = 0.002) decreased significantly in the rehabilitation group but not in the control population. Similar significant reductions in HSCRP occurred in the rehabilitation patients regardless of whether they received statin therapy or lost weight.ConclusionsTherapeutic lifestyle changes effected through a three-month cardiac rehabilitation program significantly improved numerous cardiac risk factors. Through this holistic approach to secondary prevention, we observed significant reductions in HSCRP levels. These findings identify another clinical modality of reducing HSCRP beyond use of statin drugs and suggest an additional benefit of formal phase II cardiac rehabilitation and exercise training programs.