Rationale for the short term use of intravenous milrinone under hemodynamic guidance in patients with severe systolic heart failure

Patients with severe systolic heart failure have a decrease in both number and function of cardiac beta receptors, which may result in a poor inotropic response to I.V. beta-adrenergic agonists such as dobutamine. The I.V. use of the phosphodiesterase inhibitor milrinone, which is a combined positive inotrope/vasodilator in this patient population, is a more rational choice, especially if heart failure is chronic. Many of these patients may also be referred for consideration for cardiac transplantation, for which the use of invasive hemodynamic monitoring is typically necessary to determine whether severe hemodynamic compromise and pulmonary hypertension are reversible with therapy. The use of hemodynamically guided I.V. vasodilator therapy has also been extensively described as a tool to optimize oral vasodilator therapy and predict prognosis in patients evaluated for cardiac transplantation. This review summarizes the important studies supporting the rationale for and benefits of using I.V. milrinone under hemodynamic guidance in this patient population. (c)2000 by CHF, Inc.     

Mildly dilated congestive cardiomyopathy. Use of prospective diagnostic criteria and description of the clinical course without heart transplantation

Prognosis in classically described dilated congestive cardiomyopathy has been reported to be related to ventricular size. Mildly dilated congestive cardiomyopathy (MDCM) has been defined as end-stage heart failure of unknown etiology (New York Heart Association class IV, left ventricular ejection fraction less than 30%), occurring with neither typical hemodynamic signs of restrictive myopathy nor significant ventricular dilatation (less than 15% above normal range). The present study includes follow-up in 12 nontransplant patients. In the first 4 months after diagnosis, two patients improved and are living, and two showed cardiac dilation and clinical deterioration and died. Six of the remaining eight with persistent MDCM died (four with intractable heart failure and two, sudden deaths) without change in ventricular size before death, despite medical therapy over 20 +/- 8 months. Eight comparable transplanted patients with persistent MDCM demonstrated improved total survival by life table analysis (p less than 0.05). A family history of congestive cardiomyopathy was found in nine of 16 patients (56%) with persistent MDCM. Nontransplant patients were older (p less than 0.02), but other findings were similar in the two groups. Endomyocardial biopsies available in 14 of 16 cases showed little or no myofibrillar loss in spite of severe hemodynamic impairment. The degree of myofibrillar loss did not correlate with hemodynamic parameters but showed good correlation with left ventricular size, that is, five of six patients with no myofibrillar loss had normal ventricular size, whereas all eight patients with mild myofibrillar loss had mild cardiomegaly (p less than 0.002). Our current experience suggests a somewhat variable but negative prognosis after prospective diagnosis of MDCM, with poor survival in patients with persistence of the original diagnostic features during follow-up. Preservation of heart size in MDCM is probably related to lack of significant myofibrillar loss. Thus, irrespective of heart size or myofibrillar preservation on biopsy, heart transplantation should be strongly considered in MDCM if signs of severe cardiac dysfunction persist despite therapy.     

Selection of patients for cardiac transplantation

Selection of potential cardiac recipients is not a simple process. Identification of patients who are declining from end-stage cardiac disease and may be expected to die within 12 months or less and deciding which of a number of cardiac invalids are reasonable candidates for cardiac transplantation involves prognostication as well as a working knowledge of the expected benefits and survival rates in cardiac transplantation. Screening by means of the currently accepted contraindications for cardiac transplantation is somewhat more difficult in 1986 than it was 10 years ago when these contraindications were changing less rapidly. However, for optimal use of the limited supply of donor organs and maintenance of reasonable survival rates such screening is absolutely necessary. A second area of restriction that is less approachable by the physician is that of financial limitations. It would appear that the working poor and lower middle class may be deprived of the opportunity for cardiac transplantation much as they are deprived of the opportunity for optimal medical care in our society today.     

Echocardiographic predictors of adverse outcomes in primary pulmonary hypertension

OBJECTIVES: The aim of this study was to evaluate the relationships between echocardiographic findings and clinical outcomes in patients with severe primary pulmonary hypertension (PPH).BACKGROUND: Primary pulmonary hypertension is associated with abnormalities of right heart structure and function that contribute to the poor prognosis of the disease. Echocardiographic abnormalities associated with PPH have been described, but the prognostic significance of these findings remains poorly characterized. METHODS: Echocardiographic studies, invasive hemodynamic measurements and 6-min walk tests were performed and outcomes prospectively followed in 81 patients with severe PPH. Subjects were participants in a 12-week randomized trial examining the effects of prostacyclin plus conventional therapy compared with conventional therapy alone. RESULTS: During the mean follow-up period of 36.9 +/- 15.4 months, 20 patients died and 21 patients underwent transplantation. Pericardial effusion (p = 0.003) and indexed right atrial area (p = 0.005) were predictors of mortality. Pericardial effusion (p = 0.017), indexed right atrial area (p = 0.012) and the degree of septal shift in diastole (p = 0.004) were predictors of a composite end point of death or transplantation. In multivariable analyses incorporating clinical, hemodynamic and echocardiographic variables, pericardial effusion and an enlarged right atrium remained predictors of adverse outcomes. Six-minute walk results, mixed venous oxygen saturation and initial treatment randomization were also independently associated with a poor prognosis. CONCLUSIONS: Pericardial effusion, right atrial enlargement and septal displacement are echocardiographic abnormalities that reflect the severity of right heart failure and predict adverse outcomes in patients with severe PPH. These characteristics may help identify patients appropriate for more intensive medical therapy or earlier transplantation.     

Surgical approaches to dilated cardiomyopathy

Heart failure is one of the leading causes of hospitalization in the United States today. Congestive heart failure is a chronic progressive disease with the common central element being the remodeling of the cardiac chamber associated with ventricular dilation. Secondary mitral regurgitation is a complication of end-stage cardiomyopathy and is associated with a poor prognosis. Historically, these patients were not considered operative candidates due to the high morbidity and mortality in this patient population. Heart transplantation is now considered the standard of treatment for select patients with end-stage heart disease, however, it is only applicable to a small number of patients. In an effort to address this problem, newer and alternative surgical approaches are evolving, including mitral valve annuloplasty, the Batista myoplasty, and cardiomyoplasty. When these operative techniques that alter the shape of the left ventricle are utilized, in combination with optimal medical management for heart failure, survival is improved and patients can avoid or postpone transplantation.     

Poor survival of patients with idiopathic cardiomyopathy considered too well for transplantation

Although the success of cardiac transplantation has encouraged earlier referral of potential candidates, those with mild symptoms of heart failure are frequently considered "too well" for transplantation. Outcome was investigated for 28 patients with non-ischemic dilated cardiomyopathy and ejection fraction of 25 percent or less who were denied transplantation due to lack of severe symptoms. One-year survival without transplantation was 46 percent. Low stroke volume and history of ventricular arrhythmias were independent predictors of early mortality. High risk, defined as either stroke volume of 40 ml or less or history of ventricular arrhythmia, identified 13 of 14 patients who did not survive one year and only one of 12 one-year survivors (p less than 0.001). Low stroke volume predicted hemodynamic failure (p less than 0.05) whereas arrhythmic history predicted sudden death (p less than 0.001). Clinical status improved in only six patients, all of whom had symptom duration of seven or less months at initial evaluation (p less than 0.001). Thus, patients referred to transplantation for dilated cardiomyopathy with an ejection fraction of 25 percent or less have a poor prognosis even if symptoms are mild. Patients with high hemodynamic risk may require early transplantation, whereas those with high arrhythmia risk may require other aggressive therapy in order to avoid transplantation until symptoms become severe.     

Cardiac hemodynamic and coronary angiographic characteristics of patients being evaluated for liver transplantation

With improved survival after liver transplantation (LT), the referral of older candidates has increased. The increasing demand for, and the decreased supply of, liver donors makes careful preoperative cardiac risk assessment imperative. There is a paucity of information regarding the cardiac characteristics of patients being referred for LT in the current era. This study aimed to describe the cardiac hemodynamic and coronary angiographic characteristics of a cohort of patients with end-stage liver disease without known coronary artery disease (CAD) being evaluated for LT. One hundred sixty-one consecutive patients aged>or=45 years with end-stage liver disease who were referred for right- and left-sided cardiac catheterization as part of a liver transplant evaluation were identified. There was a high prevalence of atherosclerotic risk factors; half had hypertension or diabetes, and more than half had >or=2 coronary risk factors other than age. There was a high prevalence of CAD, with 26% having unknown moderate to severe coronary narrowing. Patients with moderate to severe CAD were older, were more likely to be men, and were more likely to have hypertension or diabetes mellitus. Right- and left-sided filling pressures were elevated, suggesting abnormalities in left ventricular diastolic compliance. In conclusion, this study showed a high prevalence of coronary risk factors and unknown moderate to severe CAD in patients with end-stage liver disease being referred for LT.     

Mitral valve surgery in patients with ischemic and nonischemic dilated cardiomyopathy

Congestive heart failure (CHF) is a chronic, progressive disease and its central element is the remodeling of the cardiac chamber associated with ventricular dilatation. Secondary mitral regurgitation is a complication of end-stage cardiomyopathy and is associated with a poor prognosis. It is due to progressive mitral annular dilatation and alteration in the geometry of the left ventricle. A vicious cycle of continuing volume overload, ventricular dilatation, progression of annular dilatation, increased left ventricular wall tension and worsening mitral regurgitation and CHF occurs. The mainstays of medical therapy are diuretics and afterload reduction, which are associated with poor long-term survival in these patients. Historically, the surgical approach to patients with mitral regurgitation was mitral valve replacement, but these patients were not considered operative candidates because of their high morbidity and mortality. Heart transplantation is now considered standard treatment for select patients with end-stage heart disease; however, it is applicable only to a small number of patients. Mitral valve replacement in these patients is associated with adverse consequences on left ventricular systolic function resulting from interruption of the annulus-papillary muscle continuity. Preserving the mitral valve apparatus and left ventricle in mitral valve repair enhances and maintains left ventricular function and geometry with an associated decrease in wall stress. Using these operative techniques to alter the shape of the left ventricle, in combination with optimal medical management for heart failure, improves survival and may avoid or postpone transplantation.     

肾移植受者合并重症肺孢子菌肺炎的危险因素及预后分析

目的 分析肾移植受者合并重症肺孢子菌肺炎(PCP)的早期危险因素及预后.方法 收集2010年6月-2020年6月安徽省立医院诊治的65例肾移植受者合并PCP的临床资料,分别根据病情严重程度和预后情况分组,采用多因素Logistic回归分析与重症以及预后不良患者相关的危险因素.并对患者进行长期随访,采用Kaplan-Me...     

Exercise capacity for survivors of cardiac transplantation or sustained medical therapy for stable heart failure

Cardiac transplantation is predicted to improve survival for patients with severe symptoms of heart failure and ejection fraction of 20% or less, but the exercise capacity after cardiac transplantation is less than normal. Patients responding to vasodilators and diuretics have progressive improvement in exercise capacity despite low ejection fraction. We hypothesized that among patients currently considered appropriate for transplantation who could nonetheless subsequently be stabilized on medical therapy tailored to hemodynamic goals, survivors after 6 months of sustained medical therapy would demonstrate exercise capacity comparable to that of survivors of transplantation. Of 146 patients referred, 118 (81%) were discharged on tailored therapy without transplantation, and 88 (60%) were stable for at least 1 month. Stability after discharge was more likely in patients with lower right atrial pressures and better renal function on therapy. Of the 88 stable patients, 45 patients were listed for transplant, and 43 were ineligible or unwilling. From these patients, 42 survivors for more than 6 months follow-up after cardiac transplantation or tailoring of medical therapy underwent exercise testing. Baseline functional and hemodynamic status and left ventricular ejection fraction (15 +/- 4%) were not different between the transplant and sustained medical survivor groups at the time of initial evaluation. After 14 +/- 6 months, left ventricular ejection fraction had increased to 62 +/- 7% after transplantation (p less than 0.01) and only 22 +/- 9% after sustained medical therapy (p less than 0.05). However, there were no significant differences in the maximum workload, oxygen uptake, anaerobic threshold, or maximum oxygen pulse between survivors of cardiac transplantation and survivors on sustained medical therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Surgical therapy of end-stage heart failure

Heart failure is still associated with a poor prognosis despite great advances in drug therapy, so that surgical procedures are necessary in patients with end-stage cardiac failure. Cardiac transplantation was the therapy of choice during the last decades, but due to its disadvantages and the increasing scarcity of donor organs other surgical procedures were developed. Multisite pacing improves quality of life, but a longterm survival benefit remains to be proved. Coronary artery bypass grafting and valve surgery demonstrated to improve quality of life and to increase long-term survival. Ventricular assist devices are effective in bridging up to 70% of patients to cardiac transplantation, but the number of complications must be reduced. Partial left ventriculectomy may be performed with results similar to those obtained of cardiac transplantation, but long-term results are not yet available. Dynamic cardiomyoplasty and Myosplint implantation were not successful, but it must be awaited, if passive cardiomyoplasty leads to better results. Xenotransplantation is under intense investigation, but cannot be used clinically until now due to the hurdles of rejection and transfer of infectious diseases. This work provides a summary of today's knowledge about surgical procedures for end-stage heart failure.     

Patient Selection for Long-Term Mechanical Circulatory Support: Is It Ever too Early for the NYHA Class III Patient?

Heart failure is a common condition with significant morbidity and mortality. Pharmacologic and device therapies have resulted in substantial improvements in heart failure outcomes. Despite optimal therapy, 10 % of patients progress to advanced HF, characterized by progressive symptoms, poor quality of life, and poor prognosis. The “gold-standard” treatment of advanced heart failure remains cardiac transplantation. However, the number of patients with advanced heart failure far exceeds available donor organs. Left ventricular assist devices (LVADs) were initially developed to bridge patients with hemodynamic collapse to transplantation. Their use resulted in marked improvements in survival and quality of life in select patients giving rise to increased and expanded overall implantation. Despite these improvements, patient selection and timing for LVAD therapy is still evolving. In this article, we will review a brief history of LVADs, examine patient selection, and explore the currently debated expansion of LVADs to “less sick” patients.     

Lung transplantation for pulmonary hypertension

Although lung transplantation is a viable option for patients with end-stage pulmonary hypertension, it is associated with numerous problems including infection, rejection, and limited long-term survival. Because of these limitations, transplantation should only be considered for patients who are failing maximal medical therapy. Treatment options for patients with pulmonary hypertension that may serve to prolong or obviate the need for transplantation include anticoagulation with warfarin, diuretics, and vasodilators such as calcium channel blockers or continuous intravenous epoprostenol (prostacyclin). The response to medical therapy should be assessed at regular intervals by evaluating exercise tolerance and hemodynamic parameters. Because waiting periods for transplantation now exceed 1.5 to 2 years in the United States, and the response to medications is unpredictable, referral for transplantation should occur when patients become symptomatic. Those who are responding well to medical therapy should be removed from the active transplant waiting list, whereas those who fail therapy should go on to transplant. Utilizing medical therapy and transplantation as complementary treatments will achieve the best potential to improve quality of life and prolong survival.     

Hepatorenales Syndrom

A rapid identification of the disease and classification as orthotopic liver transplantation (OLT) candidate is necessary for patients with hepatorenal syndrome due to the poor prognosis. A successful vasoconstrictor therapy combined with albumin therapy increases the probability of survival during bridging of the critical waiting period to transplantation and leads to improved renal function following OLT. In selected cases placement of a transjugular intrahepatic portosystemic shunt (TIPS) or renal replacement therapy can represent an important therapeutic option. In cases where the prognostic factors predict a persistence of renal dysfunction after OLT, sequential or simultaneous liver-kidney transplantation can be indicated.     

LVAD destination therapy: applying what we know about psychiatric evaluation and management from cardiac failure and transplant

Left ventricular assist devices (LVADs) have evolved into long-term use as destination therapy for those with severe end-stage heart failure due to other medical risks. Success with LVAD depends on adherence to a complicated mechanical regimen, and acceptance of a life that is far from normal. Patients with LVADs share characteristics with other end-stage cardiac failure patients and those waiting for or receiving heart transplants. Understanding the more thoroughly studied issues of psychiatric disorders, adherence, and behavioral correlates of success in heart failure and transplantation may identify feasible strategies for optimizing care of LVAD patients and suggest directions for future research. Depression and distress complicate post-transplant care. Psychiatric morbidity is associated with poor outcomes, including graft rejection, non-adherence, hospitalizations, infection, and death. With a high risk of embolic neurological events, patients’ ability for self-care may be compromised. Psychiatric symptoms are underdiagnosed and undertreated, which may impact overall survival and quality of life.     

Augmentation of cardiac function in end-stage heart failure by combined use of dobutamine and amrinone

A patient with end-stage congestive cardiomyopathy had progressive hemodynamic deterioration while awaiting orthotopic heart transplantation. Attempts to support cardiovascular function by high-dose dobutamine infusions were complicated by life-threatening cardiac arrhythmias. The addition of the noncatecholamine inotropic agent, amrinone, improved ventricular performance, enabling reduction of the dose of dobutamine and resolution of the cardiac arrhythmias. Beta receptor stimulation by dobutamine combined with phosphodiesterase inhibition by amrinone may additively or synergistically augment cardiac function despite severe congestive heart failure and also have an adrenergic "sparing effect."     

Factors affecting long-term survival (>10 years) after cardiac transplantation in the cyclosporine era

OBJECTIVES: The aim of this study was to determine long-term survival (>10 years) after cardiac transplantation in the cyclosporine era and identify risk factors influencing long-term survival. BACKGROUND: Despite the availability of newer modalities for heart failure, cardiac transplantation remains the treatment of choice for end-stage heart disease. METHODS: Between 1983 and 1988, 195 patients underwent heart transplantation at a single center for the treatment of end-stage heart disease. Multivariable logistic regression analysis of pretransplant risk factors affecting long-term survival after cardiac transplantation included various recipient and donor demographic, immunologic and peritransplant variables. RESULTS: Among the group of 195 cardiac transplant recipients, actuarial survival was 72%, 58% and 39% at 1, 5 and 10 years respectively. In the 65 patients who survived >10 years, mean cardiac index was 2.91/m2 and mean ejection fraction was 58%. Transplant-related coronary artery disease (TRCAD) was detected in only 14 of the 65 patients (22%). By multivariable analysis, the only risk factor found to adversely affect long-term survival was a pretransplant diagnosis of ischemic cardiomyopathy (p = 0.04). CONCLUSIONS: Long-term survivors maintain normal hemodynamic function of their allografts with a low prevalence of TRCAD. It is possible that similar risk factors that lead to coronary artery disease in native vessels continue to operate in the post-transplant period, thereby contributing to adverse outcomes after cardiac transplantation. Aggressive preventive and therapeutic measures are essential to limit the risk factors for development of coronary atherosclerosis and enable long-term survival after cardiac transplantation.     

Efficacy of medical therapy tailored for severe congestive heart failure in patients transferred for urgent cardiac transplantation

Cardiac transplantation can only be performed in a few patients with severe congestive heart failure (CHF), due to the shortage of donor hearts. The efficacy of current medical therapy tailored for severe CHF, which has not previously been determined for transplant candidates, is of particular importance in patients considered for urgent cardiac transplantation. In this study, 50 consecutive in-patients transferred from other hospitals for urgent transplantation underwent intensive afterload reduction therapy, initially with intravenous and subsequently with oral vasodilators and diuretics tailored to hemodynamic goals. Oral regimens allowed hospital discharge without surgery for 40 of 50 patients. Nineteen of these patients had arrived on inotropic infusions and 32 had received oral vasodilators in the previous month. Cardiac index increased from 1.9 +/- 0.6 to 2.8 +/- 0.7 liters/min/m2, while pulmonary capillary wedge pressure decreased from 30 +/- 8 to 15 +/- 4 mm Hg and systemic vascular resistance decreased from 1,800 +/- 800 to 1,100 +/- 200 dynes-s-cm-5. Despite poor initial hemodynamics, ejection fraction 16 +/- 4%, serum sodium 131 +/- 6 mEq/liter, and apparent failure of previous medical therapy, actuarial survival for 24 discharged patients receiving sustained medical therapy alone was 67% at 1 year, with 67% of survivors employed full- or part-time, and 14 of 16 (88%) discharged transplant candidates survived until transplantation. By decreasing the need for transplantation to be performed urgently, increased emphasis on the design of medical therapy may allow more effective distribution of limited donor hearts.     

Use of a high thoracic epidural analgesia for treatment of end-stage congestive heart failure secondary to coronary artery disease: effect of HTEA on CHF

We present the case of a patient with end-stage congestive heart failure (NYHA class IV) secondary to ischemic cardiomyopathy despite maximally medical therapy, who needed to have a coronary artery bypass graft (CABG) surgery but whose risk was considered too high due to his deteriorating cardiac function. Cardiac sympathetic blockade by high thoracic epidural analgesia (HTEA) was added to stabilize the patient's critical condition before surgery. HTEA was performed at the T1 through T5 levels with a catheter placed percutaneously and then lidocaine (0.5%, 3-5 ml) was given as intermittent injections through the epidural catheter. The combination of HTEA treatment resulted in a rapid hemodynamic and clinical improvement and no serious catheter-related complications occurred. This case suggests that HTEA seems to be an effective and safe adjuvant therapeutics and can be used as a short-term bridge to CABG or cardiac transplantation in patients with end-stage congestive heart failure.     

The prognosis in stable and unstable angina

The average annual mortality in unselected patients with chronic stable angina is 4%. Mortality is increased in male patients and in patients who have risk factors such as hypertension, previous MI, or abnormal ECGs. We do not routinely recommend cardiac catheterization in the initial management of patients with stable angina unless the patient exhibits evidence for severe myocardial ischemia on non-invasive testing or has symptoms that are refractory to treatment. In patients who undergo cardiac catheterization, the most important determinant of survival is left ventricular function followed by the number of diseased vessels. Noninvasive testing provides important additional prognostic information to cardiac catheterization data and should be used in the decision to treat a patient medically or surgically. Mortality is increased in patients who have low exercise tolerance, exercise-induced ischemia, or a poor hemodynamic response to exercise. Unstable angina in medically treated patients is associated with a 3% to 5% hospital mortality and 7% to 8% mortality in the first year. The rate of nonfatal MI is about 8% to 10% in the first 2 weeks. We routinely recommend coronary angiography unless patients have had recent cardiac catheterization or there is a major contraindication. Mortality is increased in those who fail to respond to initial therapy, who have severe left ventricular dysfunction, and who have multivessel CAD, particularly left main CAD. The question of whether all patients with unstable angina require coronary angiography for risk stratification and possible revascularization is being addressed in the TIMI III trial.