Heart transplantation outcomes in cardiac sarcoidosis.

BACKGROUND: Cardiac sarcoidosis (CS) is a progressive inflammatory cardiomyopathy that can lead to heart failure, arrhythmia, and death. There is limited data on Orthotopic Heart Transplantation (OHT) outcomes in patients with CS. Here we examine outcomes in patients with CS who have undergone OHT at centers throughout the United States from 1987 to 2019. METHODS: This was an analysis of 63,947 adult patients undergoing OHT captured in the United Network for Organ Sharing (UNOS) registry. Patients were characterized as cardiac sarcoidosis (CS) or Non-CS. Baseline characteristics were compared using chi-square and Kruskal-Wallis Tests. Outcomes of interest included primary graft failure, patient survival, treated graft rejection, hospitalization for infection, and post-transplant malignancy. RESULTS: During the study period 227 patients with CS underwent OHT. Patients with CS were younger, had higher proportion of non-white patients, and received transplants at more urgent statuses. After multivariable modeling there was no difference in survival (HR 0.86, CI 0.59-1.3, p = 0.446) or graft failure (HR 0.849, CI 0.58-1.23, p = 0.394) between patients with CS and Non-CS. Patients with CS had lower odds of rejection (OR 0.558, CI 0.315- 0.985, p = 0.0444). Patients with CS had similar odds of hospitalization for infection and post-transplant malignancy, as Non-CS patients. CONCLUSIONS: Patients with CS and Non-CS had similar post OHT survival, odds of graft failure, hospitalizations for infection, and post-transplant malignancy. Results of this study confirm the role of heart transplantation as a viable option for patients with CS.

History of cigarette smoking and heart transplant outcomes.

Background : Active cigarette smoking (CS) is a contraindication for Orthotopic Heart Transplantation (OHT) with a recommendation that HT candidates be free from CS for at minimum 6 months prior to HT. Animal studies have shown that a history of CS is associated with increased risk of allograft rejection, but few studies have examined the association of past CS and HT outcomes. Methods : Data were analyzed from HT recipients captured in the United Network for Organ Sharing (UNOS) transplant registry. Adults aged 18-79 who underwent HT from 1987 to 2018 and with data for all covariates (N = 32,260) were included in this study. The cohort was categorized by past smoking history (CS vs non-CS). Post-transplant outcomes of interest included survival, graft failure, treated rejection, malignancy and hospitalization for infection. Baseline characteristics were compared between the two groups using the chi-squared analysis. Unadjusted associations between CS and patient survival were determined using the Kaplan-Meier estimations and confounding was addressed using multivariable Cox proportional hazards models. Results : HT recipients with a history of CS were older (55 vs 50, p = <0.0001), more likely to be Caucasian (75.7 vs 62.3, p = <0.0001), male (81.7 vs 68.2, p =< 0.0001), and diabetic (27.4 vs 24.4, p =< 0.0001). CS was associated with significantly worse survival (HR: 1.23, p < 0.0001). A history of CS was also associated with increased risk of acute rejection (OR: 1.20, p < 0.0001), hospitalization for infection (OR:1.24, p < 0.0001), graft failure (OR:1.23, p < 0.0001) and post-transplant malignancy (OR:1.43, p < 0.0001). Conclusion : A history of CS is associated with increased risk of adverse events post OHT.

Increased incidence and mortality associated with skin cancers after cardiac transplant.

Skin cancer incidence has been shown to be increased in the context of transplant-associated immunosuppression. There is, however, limited information specifically about the incidence of skin cancer after cardiac transplantation in the United States. A 10-year retrospective cohort study of 6271 heart transplants at 32 US transplant centers revealed increased postprocedure incidence of nonmelanoma and melanoma skin cancers, especially cutaneous squamous cell carcinoma, for which the incidence increased from 4- to 30-fold compared to the age and gender equivalent general population. Incidence of skin cancer in this study was consistent with prior single-center data regarding cardiac transplant patients. Comparison of all-cause mortality statistics for patients with basal cell carcinoma, squamous cell carcinoma and melanoma, respectively, demonstrated increased mortality associated with melanoma. Skin cancer screening and prophylaxis may be of some utility in reducing morbidity and mortality in cardiac transplant patients.

Outcomes after emergency department discharge with a primary diagnosis of heart failure.

BACKGROUND: Patients with decompensated chronic heart failure (CHF) are frequently evaluated in emergency departments (ED). The outcomes of such patients after discharge to the outpatient setting from the ED are not well known. Risk factors for return ED visits or subsequent hospital admission after ED discharge for CHF also are not known. METHODS: Charts were reviewed from all 112 patients discharged from the Parkland Memorial Hospital ED with a primary diagnosis of CHF from October to December 1998. A composite end point ("failure of outpatient therapy") was prespecified to be a recurrent ED visit for CHF, hospitalization for CHF, or death at 3 months after the index ED discharge. RESULTS: Within 3 months of the index ED visit, 61% of the study population met the composite end point. The median time to failure of outpatient therapy was 30 days. Univariate analysis of 27 clinical and demographic variables demonstrated the respiratory rate at presentation as the only predictor of failure of outpatient therapy (P =.02). Multivariate analysis of a model with 8 prespecified variables also demonstrated respiratory rate to be the only variable independently associated with an increased risk for the composite end point (odds ratio 1.6, 95% confidence interval 1.1-2.6, for each increase of 5 breaths/min). CONCLUSION: There is a high rate of failure of outpatient therapy (61%) in patients discharged with a primary diagnosis of CHF from an urban county hospital ED. Increased respiratory rate on presentation to the ED may be associated with adverse outcomes after ED discharge for CHF.

Race and the response to adrenergic blockade with carvedilol in patients with chronic heart failure.

BACKGROUND: The benefits of angiotensin-converting-enzyme inhibitors and beta-blockers may be smaller in black patients than in patients of other races, but it is unknown whether race influences the response to carvedilol in patients with chronic heart failure. METHODS: In the U.S. Carvedilol Heart Failure Trials Program, 217 black and 877 nonblack patients (in New York Heart Association class II, III, or IV and with a left ventricular ejection fraction of no more than 0.35) were randomly assigned to receive placebo or carvedilol (at doses of 6.25 to 50 mg twice daily) for up to 15 months. The effects of carvedilol on ejection fraction, clinical status, and major clinical events were retrospectively compared between black and nonblack patients. RESULTS: As compared with placebo, carvedilol lowered the risk of death from any cause or hospitalization for any reason by 48 percent in black patients and by 30 percent in nonblack patients. Carvedilol reduced the risk of worsening heart failure (heart failure leading to death, hospitalization, or a sustained increase in medication) by 54 percent in black patients and by 51 percent in nonblack patients. The ratios of the relative risks associated with carvedilol for these two outcome variables in black as compared with nonblack patients were 0.74 (95 percent confidence interval, 0.42 to 1.34) and 0.94 (95 percent confidence interval, 0.43 to 2.05), respectively. Carvedilol also improved functional class, ejection fraction, and the patients' and physicians' global assessments in both the black patients and the nonblack patients. For all these measures of outcome and clinical status, carvedilol was superior to placebo within each racial cohort (P<0.05 in all analyses), and there was no significant interaction between race and treatment (P> 0.05 in all analyses). CONCLUSIONS: The benefit of carvedilol was apparent and of similar magnitude in both black and nonblack patients with heart failure.

Heart failure in blacks: etiologic and epidemiologic differences.

Heart failure in black Americans has become a cardiovascular conundrum of increasing clinical significance. Over 60% of black patients with heart failure have an antecedent history of hypertension as a putative cause of left ventricular (LV) dysfunction, whereas only 30% have coronary artery disease as the suspected cause of LV dysfunction. Once affected with heart failure, the natural history of the disease becomes worrisome: LV dysfunction is more advanced, the severity of the disease is worse, the hospitalization rate is higher, and the mortality rate is at least 30% higher than that of white Americans. When treated in a conventional manner, available data have been inconsistent, and reliable drug efficacy has not been demonstrated. These differences do not appear to be due to socioeconomic factors. It is quite possible that unique pertubations in the neurohormonal environment may explain differences in the natural history of heart failure in blacks and yield new targets of therapy.

Clinical trials of beta-blockers in heart failure: a class review.

Heart failure remains a clinically challenging illness, with increasing incidence and prevalence and a high risk of mortality. The introduction of agents that interfere with the neurohormonal response to chronic left-ventricular dysfunction has resulted in improved patient outcomes. Owing to slowed disease progression and reduced mortality, angiotensin-converting enzyme (ACE) inhibitors are indicated in all patients with heart failure. New data indicate that in appropriate patients, beta-blocker therapy relieves the symptoms associated with heart failure, reduces hospitalizations, and improves survival when added to standard therapy. Questions still remain regarding the ideal use of beta blockers in heart failure, and ongoing trials will attempt to clarify those points.

Noninvasive assessment of hemodynamics: an emphasis on bioimpedance cardiography.

Evaluation of the hemodynamic response in heart failure is a useful adjunct in clinical management. Invasive monitoring has been the accepted gold standard of hemodynamic assessment but carries with it significant associated risks. Noninvasive hemodynamic assessment in heart failure previously has been either unreliable or difficult to obtain. Bioimpedance relies on the proportional change in the conduction of alternating current applied across the thorax as a function of blood volume in the heart and great vessels. Stroke volume, cardiac output, thoracic fluid content, and measures of diastolic function can be determined with bioimpedance. Impedance cardiography is becoming an accepted method for safe, reliable, and reproducible assessment of hemodynamics in heart failure.

Improving patient outcomes by pooling resources (the Texas Heart Care Partnership experience).

The morbidity and mortality associated with cardiovascular disease presents an enormous humanistic and economic burden in the United States. In Texas, cardiovascular disease has been the leading cause of death since 1950. Risk-factor modification has been targeted in the secondary prevention of cardiovascular disease, including lipid management, smoking cessation, improved control of blood pressure, physical activity, weight management, the use of antiplatelet agents/anticoagulants, angiotensin-converting enzyme (ACE) inhibitors in congestive heart failure, beta blockers after myocardial infarction, and estrogen replacement therapy. The Heart Care Partnership (HCP) is a multifaceted interactive program designed to improve risk-factor management in the secondary prevention of cardiovascular disease through physician education, participation, and consensus development in addition to practice improvement processes and patient education. Development and implementation of the Texas HCP was a joint effort of the Texas Medical Association, the Texas Affiliate of the American Heart Association, and Merck & Co. This program helps hospitals improve the quality of care and outcomes for patients with heart disease. Program resources include educational workshops, quality improvement processes, and patient educational materials. HCP workshops address the treatment gap, define optimal care, and help define institution-specific plans for treating heart disease. Quality-improvement processes provide hospitals with baseline data and tools to improve and measure outcomes over time. The HCP workshops are provided as a combination of lectures, interactive discussions, and small group planning sessions designed to encourage audience participation. Upon completing the HCP program, participants are able to (1) describe the evidence-based medicine supporting secondary prevention of cardiovascular disease; (2) identify and prioritize cardiovascular disease risk factors for secondary prevention; (3) identify barriers to and solutions for implementing secondary prevention; and (4) develop site-based plans for cardiovascular risk-factor modification with definite time lines for implementation ("care maps"). The HCP's initial audit of medical practices indicates that Texas appears to share the same deficiencies in the secondary prevention of cardiovascular disease as the rest of the country. However, improvements can be demonstrated in both the hospital and physician office settings through the HCP. The HCP facilitated the cooperation of the medical community in the state of Texas to work together in a synchronized, communicative manner to decrease coronary events. This partnership represents a watershed event in the history of Texas medicine. It is the first time that such a statewide team approach to address a public health issue has been initiated. In the past, medical organizations within the state have had disparate goals and multiple strategies for achieving them.

Tailored therapy using dobutamine and nitroglycerin in advanced heart failure.

In 29 patients with advanced heart failure, therapy tailored to hemodynamic goals was attempted using an initial infusion of dobutamine and nitroglycerin (the latter in those with pulmonary hypertension) followed by escalating doses of oral vasodilators. In the 23 patients who were weaned from inodilator therapy, significant improvements in hemodynamic parameters and a low 90-day hospital readmission rate were documented.

The MR appearance of volume overload in the lower extremities.

PURPOSE: Our goal was to describe the MR findings of volume overload (VO) in the lower extremities. METHOD: Fifteen individuals were studied, including eight healthy controls and seven patients with VO (four cardiac, three renal). MR evaluation included various SE techniques. Edema detection, localization, and symmetry were assessed subjectively. Relaxation time estimates were also made of the subcutaneous tissue, marrow, and three muscles. RESULTS: Subcutaneous tissue was markedly edematous in seven of seven patients and asymmetric in four of seven, whereas marrow was normal in all patients. Muscle edema was mild and asymmetric in six and two of seven patients, respectively. Perifascial fluid collections were identified in six of seven patients. CONCLUSION: Subcutaneous tissue edema is the dominant feature of VO in the lower extremities. Perifascial fluid is common but does not necessarily distribute symmetrically. Muscle edema is relatively mild. These findings should aid in identifying VO as the potential cause of swelling in patients with swollen legs.

An individualized protocol is more accurate than a standard protocol for assessing exercise capacity after heart transplantation.

BACKGROUND: Subjective improvement and normalization of exercise tolerance are reported by most of patients after heart transplantation. However, objective measurements often do not confirm the subjective improvement. This disparate observation may be related to the methods used to test exercise tolerance. We postulated that an individualized, more gradual exercise protocol might allow a more accurate assessment of exercise tolerance than standard protocols for patients with transplanted, denervated hearts. METHODS: Eleven stable heart recipients exercised on a treadmill using two different protocols. Protocol A was a standard Naughton's protocol, and protocol B was an individualized Naughton's protocol, in which the slope of the treadmill was increased only after a steady state in heart rate and oxygen consumption had been achieved and maintained for 30 seconds. RESULTS: Patients exercised longer and reached a higher workload with protocol B than with protocol A. Time to anaerobic threshold was significantly prolonged by protocol B. Minute ventilation and oxygen consumption at anaerobic threshold were significantly higher with protocol B than with protocol A. At peak exercise, heart rate, oxygen consumption, oxygen pulse, and minute ventilation were similar with the two protocols and exceeded 75% of the predicted corresponding maximal values for a normal matched population. CONCLUSIONS: The use of an individualized, gradual exercise protocol for heart transplant recipients detected a significantly better submaximal exercise capacity than a standard protocol, which is more consistent with the subjective improvement in functional capacity in this population.

Treatment of hyperlipidemia after heart transplantation and rationale for the Heart Transplant Lipid Registry.

Hyperlipidemia occurs frequently after heart transplantation, and accelerated coronary artery disease remains the major cause of morbidity and mortality in patients who survive more than 1 year after heart transplantation. However, the risks and benefits of lipid-lowering therapy after heart transplantation remain poorly defined, and national guidelines for lipid-lowering drug therapy do not specifically address treatment of dyslipidemia in transplant recipients. Since the initial reports in the 1980s of rhabdomyolysis in heart transplant patients receiving high-dosage lovastatin, results of 11 post-transplantation series that used lovastatin, simvastatin, or pravastatin at lower dosages as drug monotherapy have been published. These studies have shown an overall 1% incidence of rhabdomyolysis, defined as creatine kinase > 10 times the upper limit of normal plus muscle symptoms. One randomized, controlled prospective trial has investigated the effects of lipid-lowering pharmacotherapy on patient outcome in cardiac transplant recipients. At 1-year follow-up in this nonblinded, single-center trial, patients treated with pravastatin (20 or 40 mg/day) initiated within 2 weeks of transplantation had a significant reduction in mortality rate and a significantly lower incidence of transplant arteriopathy. A number of important issues remain unanswered regarding treatment guidelines in patients with hyperlipidemia after heart transplantation. In January 1995 we began the Heart Transplant Lipid Registry, with 12 participant centers, to gather data prospectively on the efficacy and safety of lipid-lowering drugs in the treatment of dyslipidemia after heart transplantation.

Central venous pressure in space.

Gravity affects cardiac filling pressure and intravascular fluid distribution significantly. A major central fluid shift occurs when all hydrostatic gradients are abolished on entry into microgravity (microG). Understanding the dynamics of this shift requires continuous monitoring of cardiac filling pressure; central venous pressure (CVP) measurement is the only feasible means of accomplishing this. We directly measured CVP in three subjects: one aboard the Spacelab Life Sciences-1 space shuttle flight and two aboard the Spacelab Life Sciences-2 space shuttle flight. Continuous CVP measurements, with a 4-Fr catheter, began 4 h before launch and continued into microG. Mean CVP was 8.4 cmH2O seated before flight, 15.0 cmH2O in the supine legs-elevated posture in the shuttle, and 2.5 cmH2O after 10 min in microG. Although CVP decreased, the left ventricular end-diastolic dimension measured by echocardiography increased from a mean of 4.60 cm supine preflight to 4.97 cm within 48 h in microG. These data are consistent with increased cardiac filling early in microG despite a fall in CVP, suggesting that the relationship between CVP and actual transmural left ventricular filling pressure is altered in microG.

Risk factors for early, cumulative, and fatal infections after heart transplantation: a multiinstitutional study.

BACKGROUND AND METHODS: By multivariable analysis, risk factors were identified for initial infection of any type, cumulative infections during the first 6 months and fatal infection among 2210 heart transplant recipients at 30 institutions. RESULTS AND CONCLUSIONS: Of the 1218 infections in 695 patients, bacterial infections were most frequent (47%), followed by viral (42%), fungal (8%), and protozoal (4%). Risk factors for earlier infection included older recipient age (p < 0.0001), ventilator support at time of transplant (p < 0.0001), ventricular assist device at time of transplant (p = 0.02), OKT3 induction therapy (p < 0.0001), donor black race (p = 0.0007), and positive donor cytomegalovirus serology (for cytomegalovirus infection) (p = 0.0007). Cumulative infections during the first 6 months were increased by older recipient age (p < 0.0001), ventilator support at transplant (p = 0.0004), ventricular assist at transplant (p = 0.009), Black donor (p = 0.03), female donor (p = 0.03), and OKT3 induction therapy (p = 0.005). The actuarial freedom from fatal infection was 96% at 1 year and 95% at 3 years. Risk factors for death from infection included very old (p = 0.002) and very young recipients (p = 0.004), ventilator support at time of transplant (p = 0.004), older donor (p < 0.0001), and longer donor ischemic time (p = 0.02). The risk of death from infection within the first 3 months exceeded 20% among older recipients (> 55 years) on ventilator support at time of transplantation who received an older (> 50 years) donor heart.

Triple-drug immunosuppression with steroid discontinuation by six months after heart transplantation.

BACKGROUND: Triple-drug immunosuppression with cyclosporine, azathioprine, and prednisone is associated with complications which might be reduced by steroid withdrawal. METHODS: In two groups of heart transplant recipients maintained on an identical regimen of cyclosporine and azathioprine, prednisone was withdrawn in group I patients (n = 35) by 6 months after transplantation, whereas in group II patients (n = 49) prednisone was never discontinued. RESULTS: Survival was similar in the two groups. The incidence of acute graft rejection was significantly higher in group I (54%) than in group II (12%), whereas infective complications were significantly lower in group I than in group II (0.63 versus 1.02 episode/patient). The degree of posttransplantation weight gain, lipid abnormalities, and incidence of hypertension were not modified by the fast tapering of prednisone, whereas the incidence of cataract and compression fracture and the degree of bone loss were significantly reduced in group I. Graft function and incidence of coronary artery disease were similar in the two groups. CONCLUSIONS: The present data suggest that prednisone can be safely withdrawn in heart transplant recipients without jeopardizing survival and graft function. Longer follow-up is needed to assess the full impact of early withdrawal of steroids from triple-drug immunosuppression, especially on long-term graft function and incidence of coronary artery disease. Benefits of early steroid withdrawal included a reduction in bone loss, which might ultimately have a major positive impact on the extent of long-term rehabilitation and exercise tolerance after heart transplantation.