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.

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.

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.

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.

Survival in congestive heart failure: have we made a difference?

Congestive heart failure (CHF) affects approximately 400,000 new patients each year in the United States, resulting in death in more than 50% within five years, with traditional therapy including digitalis and diuretics. The aging of the population will only serve to aggravate this problem. Surgical treatment of CHF is a viable option in a minority of cases; a total of no more than 2,000 heart transplantation procedures were performed in the United States in 1988. Therefore, if survival is to improve in patients with CHF, effective alternative medical therapy may need to be added to or substituted for more traditional therapy. Vasodilator therapy with the angiotensin-converting enzyme inhibitors captopril and enalapril, or the combination of hydralazine and isosorbide dinitrate, improves survival in patients with severe heart failure when added to treatment with digitalis and diuretics. Nevertheless, the mortality rate remains extremely high once this stage of the disease process is reached. The prevention of left ventricular dilatation and remodeling, before the occurrence of overt heart failure, is the focus of much attention. Interventions that limit or interrupt the disease process at an even earlier stage will be necessary to make a major impact on survival.

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.

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.

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.

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.

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.

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.

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.

Role of atrial natriuretic peptide in systemic responses to acute isotonic volume expansion.

Atrial natriuretic peptide (ANP) may activate multiple mechanisms that protect against circulatory volume overload. We hypothesized that a temporal relationship exists between increases in cardiac filling pressure and plasma ANP concentration and also between ANP elevation and vasodilation, fluid movement from plasma to interstitium, and increased urine volume (UV). We infused 30 ml/kg isotonic saline at 100 ml/min in seven supine male subjects and monitored responses for 3 h postinfusion. Right atrial pressure (RAP) was measured via a central catheter. ANP (pmol/l) was measured by radioimmunoassay. Transcapillary fluid transport (TFT) equaled infused volume minus UV, insensible fluid loss, and change in plasma volume (PV, measured with Evan's blue). Systemic vascular resistance (SVR) was calculated as (mean arterial pressure-RAP)/cardiac output (determined by acetylene rebreathing). Plasma oncotic pressure (OP) was measured directly. During infusion, mean TFT (+/- SE) increased from net reabsorption during control of 111 +/- 27 ml/h to net filtration of 1,219 +/- 143 ml/h (P < 0.01). At end infusion, mean RAP, heart rate, and PV exhibited peak increases of 146, 23, and 27%, respectively. Concurrently, SVR and OP achieved nadirs 29 and 31% below control, respectively. Mean plasma ANP and UV peaked (45 and 390%, respectively) at 30 min postinfusion. Systemic vasodilation and capillary filtration resulted from and compensated for infusion-induced circulatory pressure increases and hemodilution. By 1 h postinfusion, most cardiovascular variables had returned toward control levels, and net reabsorption of extravascular fluid ensued.(ABSTRACT TRUNCATED AT 250 WORDS)

Physical fitness and cardiovascular regulation: mechanisms of orthostatic intolerance.

We studied three groups of eight men each--high, mid, and low fit (peak O2 consumption 60.0 +/- 0.8, 48.9 +/- 1.0, and 35.7 +/- 0.9 ml.min-1.kg-1)--to determine the mechanism of orthostatic intolerance in endurance athletes. Tolerance was defined by progressive lower body negative pressure (LBNP) to presyncope. Maximal calf vascular conductance (Gmax) was measured. The carotid baroreflex was characterized using both stepwise R-wave-triggered and sustained (2 min) changes in neck chamber pressure. High-fit subjects tended to have lower LBNP tolerance than mid- and low-fit subjects but similar baroreflex responses. Subjects with poor LBNP tolerance had larger stroke volumes (SV) (120 +/- 6 vs. 103 +/- 3 ml) and greater decline in SV with LBNP to -40 mmHg (40 +/- 2 vs. 26 +/- 4%). Stepwise multiple linear regression analysis revealed that Gmax and steady-state gain of the carotid baroreflex contributed significantly toward explaining interindividual variations in LBNP tolerance. Thus endurance athletes may have decreased LBNP tolerance, but apparently not as a simple linear function of aerobic fitness. Orthostatic tolerance depends on complex interactions among functional characteristics that appear both related (Gmax and SV) and unrelated (baroreflex function) to fitness or exercise training.

Differential reflex control of forearm and calf resistance vessels by chemosensitive cardiac afferent activation.

The aim of this study was to determine whether chemosensitive ventricular afferent activation in humans evokes a diffuse pattern of reflex vasodilation involving the skeletal muscle circulation of all the extremities or a highly specified pattern of vasodilation that is limited to the rather small vascular bed of the forearm. In 10 patients with innervated ventricles and 7 patients with denervated ventricles resulting from heart transplantation, we performed simultaneous plethysmographic recordings of blood flow in the forearm and calf during chemosensitive ventricular afferent activation with intracoronary Renografin. In patients with innervated ventricles, intracoronary Renografin evoked directionally opposite vascular responses in the forearm and calf: forearm resistance decreased from 50 +/- 11 to 31 +/- 8 units, whereas calf resistance increased from 42 +/- 7 to 59 +/- 9 units (P < 0.05, calf vs. forearm). Forearm vasodilation was eliminated after heart transplantation, indicating that this is a reflex response caused by ventricular afferents. In contrast, calf vasoconstriction was well preserved despite ventricular deafferentation, indicating that this response is caused by mechanisms other than ventricular afferent activation, possibly the sinoaortic baroreceptors. Taken together, these findings document a remarkable degree of specificity in the effects of cardiac afferent activation on the reflex regulation of regional vasomotor tone in humans.

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.

Combined thrombolytic therapy for prosthetic mitral valve thrombosis.

Prosthetic valve thrombosis is associated with high mortality. The treatment of choice remains operation. This is a case report of the successful combination therapy of tissue plasminogen activator and urokinase for an isolated thrombosed prosthetic mitral valve in a postpartum patient in whom operation was thought to carry an unacceptable risk. Combined thrombolytic therapy or therapy with a single agent with a long half-life and a prolonged infusion time is suggested as an emergent treatment option for prosthetic mitral valve thrombosis.

Congestive heart failure.

Congestive heart failure (CHF) is not a single entity but a symptom complex that may represent the consequence of mechanical abnormalities, myocardial abnormalities, and/or disturbances of cardiac rhythm. In turn, it affects virtually every organ system in the body. This review focuses on CHF due to systolic dysfunction of the left ventricle, which comprises the majority of cases of this condition. Recent data suggest that CHF may be the most frequent primary diagnosis in patients on medical services in nonmilitary hospitals in this country: it affects approximately 2% of the United States population, or some 4 million people. The mortality rate for CHF is also worse than for many forms of cancer; thus, new therapeutic alternatives are imperative. In order to devise new therapeutic strategies, a detailed understanding of the pathophysiology of this condition is required. The relative advantages and disadvantages of various pharmacologic and nonpharmacologic approaches are considered in detail. Certain medications, such as the angiotensin converting enzyme (ACE) inhibitors, have been shown to improve survival, and heart transplantation is clearly life-saving for those who are eligible for this therapy. However, the real challenge is to devise strategies to prevent the occurrence of heart failure, or interrupt its progress at a very early stage.

Severe congestive heart failure. How successful are drug and transplant therapies?

Severe congestive heart failure is a fatal illness. Aggressive use of proven medical regimens, including vasodilators and angiotensin-converting enzyme inhibitors, may prolong survival time for some patients. Those with refractory symptoms and seriously reduced left ventricular function, impaired exercise capacity, and complex or frequent ventricular arrhythmias should be considered for cardiac transplantation. Candidacy for transplantation is based on the absence of other illnesses that would limit survival or diminish the likelihood of success of the transplant. With the introduction of potent immunosuppressive agents, particularly cyclosporine (Sandimmune), survival rates after transplantation have improved to 90% at 1 year. Major problems include organ rejection, serious infection, development of coronary artery disease in the transplanted heart, and the limited donor organ supply.