Sympathetic activation in heart failure.

Sympathetic activation has been long appreciated exclusively as a fundamental compensatory mechanism of the failing heart and, thus, welcome and to be supported. In the initial clinical phases of heart failure (HF), the sympathetic nervous system overdrive plays a compensatory function aimed at maintaining an adequate cardiac output despite the inotropic dysfunction affecting the myocardium. However, when the sympathetic reflex response is exaggerated it triggers a sequence of unfavourable remodelling processes causing a further contractile deterioration that unleashes major adverse cardiovascular consequences, favouring the HF progression and the occurrence of fatal events. Eventually, the sympathetic nervous system in HF was demonstrated to be a 'lethality factor' and thus became a prominent therapeutic target. The existence of an effective highly specialized intracardiac neuronal network immediately rules out the old concept that sympathetic activation in HF is merely the consequence of a drop in cardiac output. When a cardiac damage occurs, such as myocardial ischaemia or a primary myocardial disorder, the adaptive capability of the system may be overcame, leading to excessive sympatho-excitation coupled with attenuation till to abolishment of central parasympathetic drive. Myocardial infarction causes, within a very short time, both a functional and anatomical remodelling with a diffuse up-regulation of nerve growth factor (NGF). The subsequent nerve sprouting signal, facilitated by a rise in the levels of NGF in the left stellate ganglion and in the serum, triggers an increase in cardiac nerve density in both peri-infarct and non-infarcted areas. Finally, NFG production decreases over time, supposedly as an adaptative response to the prolonged exposure to sympathetic overactivity, leading in the end to a reduction in sympathetic nerve density. Accordingly, NGF levels were markedly reduced in patients with severe congestive heart failure. The kidney is the other key player of the sympathetic response to HF as it indeed reacts to under-perfusion and to loop diuretics to preserve filtration at the cost of many pathological consequences on its physiology. This vicious loop ultimately participates to the chronic and disruptive sympathetic overdrive. In conclusion, sympathetic activation is the natural physiological consequence to life stressors but also to any condition that may harm our body. It is the first system of reaction to any potential life-threatening event. However, in any aspect of life over reaction is never effective but, in many instances, is, actually, life threatening. One for all is the case of ischaemia-related ventricular fibrillation which is, strongly facilitated by sympathetic hyperactivity. The take home message? When, in a condition of harm, everybody is yelling failure is just around the corner.

Cryoballoon ablation for atrial fibrillation guided by real-time three-dimensional transoesophageal echocardiography: a feasibility study.

AIMS: Cryoballoon ablation (CBA; Arctic Front, Medtronic) has proven very effective in achieving pulmonary vein isolation. Real-time three-dimensional transoesophageal echocardiography (RT 3D TEE) is a novel technology, which permits detailed visualization of cardiac structures in a 3D perspective. The aim of the present study was to assess the feasibility, advantages, and safety of RT 3D TEE in guiding CBA in a series of patients affected by paroxysmal atrial fibrillation. METHODS AND RESULTS: Forty-five patients (34 males, mean age: 63 ± 12 years) underwent CBA guided by 3D TEE. A total of 190 veins could be documented by TEE. Real-time three-dimensional transoesophageal echocardiography successfully guided the operator to position the CB in the pulmonary vein (PV) ostium and obtain complete occlusion in all 190 (100%) veins. Transoesophageal echocardiography identified leakages in 25 (13%) veins led to successful elimination of PV-left atrium (LA) backflow by guiding correct balloon repositioning. In four (2%) veins, this imaging tool led to perform successful pull-down manoeuvres. After a mean 2.6 ± 1.4 applications, isolation could be documented in 190 (100%) PVs. Median procedural and fluoroscopy times were 145 and 24 min. During a median follow-up of 278 days, 37 (82%) patients did not experience atrial fibrillation recurrence following a 3-month blanking period. CONCLUSION: Cryoballoon ablation is safe and feasible under RT 3D TEE guidance. This imaging tool permits perfect visualization of all PV ostia and neighbouring LA structures. Most importantly, it proved very efficient in guiding the operator to achieve complete occlusion and successful isolation in all veins.

Heart transplantation in mildly diabetic patients.

From 1985 to 1989, 67 heart transplantations were performed in our hospital, 6 of them in non-insulin-dependent (type II) diabetic patients. Six pretransplantation type II diabetic male heart recipients (mean +/- SD age 50.0 +/- 7.3 yr) were compared with 61 nondiabetic recipients (mean age 44.5 +/- 11.0 yr; 55 men, 6 women) to define whether a different posttransplantation prognosis may be caused by pretransplantation diabetes. Before transplantation, all diabetic recipients (3 newly diagnosed and 3 with diabetes duration of 5, 6, and 12 yr, respectively) were in good glycemic control (mean fasting blood glucose 7.95 +/- 1.62 mM, mean HbA1c 7.6 +/- 0.2%). None had ocular or renal microangiopathic complications, 5 were treated only with diet, and 1 was treated with oral hypoglycemic agents. All recipients were treated with the same immunosuppressive protocol (cyclosporin, prednisone, and since 1986, azathioprine and antilymphocyte globulin), and mean dose and blood levels of cyclosporin were not significantly different between diabetic and nondiabetic recipients. After heart transplantation (mean follow-up 558 +/- 340 days in diabetic and 379 +/- 338 in nondiabetic recipients), the mortality rate and complications (i.e., rejection episodes, supplementary immunosuppressive treatments, major and minor infections, arterial hypertension, and graft atherosclerosis) showed no significant differences except for the more frequent arterial hypertension in diabetic recipients (P less than 0.05), although pretransplantation incidence of hypertension was lower in diabetic candidates.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute rejection after heart transplantation: noninvasive echocardiographic evaluation.

OBJECTIVES: The purpose of this study was to assess the reliability of echocardiography in the noninvasive diagnosis of acute rejection in heart transplant recipients. BACKGROUND: Although echocardiographic results seem to correlate well with allograft rejection, published data are limited and contradictory. METHODS: In 130 transplant recipients, 1,400 serial echocardiograms were recorded within 24 h of endomyocardial biopsy. Increased wall thickness, myocardial echogenicity, pericardial effusion, shorter pressure half-time, isovolumetric relaxation time and a decrease in left ventricular ejection fraction were considered markers of rejection. RESULTS: The distribution of echocardiographic markers revealed highly significant differences between bioptically graded moderate, mild and no rejection and between untreated and treated rejection episodes (both chi-square test, p < 0.0001). Specificity was 98.6% for two markers, but sensitivity was good (80%) for only moderate rejection because of the large number of false negatives in untreated patients with mild rejection. In untreated patients, there was a highly significant difference in the number of echocardiographic criteria between a benign and nonbenign outcome (chi-square test, p < 0.0001). In treated patients, the significant difference in the variation in echocardiographic criteria between favorable and unfavorable responses after 1 week was more pronounced after 2 weeks (t test, p < 0.01 vs. < 0.001). Diastolic indexes and pericardial effusion at 2 weeks seemed to be predictive of therapeutic response. CONCLUSIONS: Poor sensitivity to mild rejection indicates that serial echocardiography cannot supplant endomyocardial biopsy in the early diagnosis of acute rejection, but it seems to be a reliable noninvasive means of identifying acute rejection requiring intensified immunosuppressive therapy and of evaluating outcome.

Super-normal 201Tl retention in hibernating myocardium: an ex-vivo study using the failing human heart.

OBJECTIVE: Although the relationship between delayed 201Tl distribution and blood flow in acutely ischemic and infarcted myocardium has been widely explored in the experimental setting, its behaviour in chronically hypoperfused dysfunctioning human myocardium has not yet been evaluated. METHODS: In tissue samples of excised failing hearts taken from ischemic (IHD) patients and idiopathic dilated cardiomyopathy (IDC) controls, we evaluated the relationship between delayed 201Tl retention (4 h redistribution), blood flow (assessed by means of 99mTc-labelled human albumin microspheres injected during transplantation) and biochemically-assessed fibrosis. 201Tl activity was expressed as the percent of the activity in the region with highest flow and the least fibrosis. RESULTS: Fibrosis and 201Tl activity were inversely related (r = -0.62, P = 0.0001). In IDC controls, low flows corresponded to uniformly preserved 201Tl retention. In IHD, 46 segments with flows < or = 0.60 ml.min-1.g-1 and 20 segments with flows > 0.60 ml.min-1.g1 showed matching delayed 201Tl retention and flow values; in the remaining 27, there was a disproportionately high tracer accumulation in comparison with flow (flow/201Tl mismatch). Despite significantly less fibrosis and lower flows, the mismatch segments showed significantly greater. 201Tl activity than the segments with concordantly high tracer retention and flow values. Conversely, at equivalent flow rates, the mismatch regions had less fibrosis than the areas with concordantly depressed 201Tl activity and perfusion. CONCLUSIONS: This super-normal 201Tl retention in hibernating myocardium may indicate a mechanism of cell adaptation to chronic hypoperfusion.

Reflex vasopressin and renin modulation by cardiac receptors in humans.

Animal studies have shown that vasopressin secretion is modulated by arterial baroreceptors and cardiopulmonary volume receptors. Whether this is the case also in humans is controversial, however. To determine whether vasopressin is reflexly modulated by cardiac volume receptors, we studied the effect on plasma vasopressin (venous blood, radioimmunoassay) of reducing venous return and left ventricular end-diastolic diameter (echocardiography) by producing a 20-minute lower body negative pressure in 14 healthy subjects (aged 49.3 +/- 3.8 years, mean +/- SEM). The data were compared with those of 14 age-matched heart-transplant recipients, i.e., subjects with cardiac denervation. In healthy subjects, lower body negative pressure at -15 mm Hg caused a modest reduction in left ventricular end-diastolic diameter (-5 +/- 3.4%) and no change in vasopressin, whereas lower body negative pressure at -37.5 mm Hg caused a more marked reduction in left ventricular end-diastolic diameter (-12 +/- 2.5%) and a small, variable, but overall statistically significant (p < 0.05) increase in vasopressin (+145 +/- 46%, p < 0.01). The left ventricular end-diastolic diameter changes induced by the two lower body negative pressure stimuli were similar in heart-transplant recipients, but the vasopressin increase seen with the lower body negative pressure at -37.5 mm Hg was abolished. The marked increase in plasma renin activity and forearm vascular resistance induced by lower body negative pressure in healthy subjects was also abolished or drastically attenuated in heart-transplant recipients.(ABSTRACT TRUNCATED AT 250 WORDS)

Lysosomal glycogen storage with normal acid maltase: a familial study with successful heart transplant.

Lysosomal glycogen storage in muscle with normal acid maltase activity is a rare inherited condition characterized by cardiomyopathy, mental retardation and mild myopathy in males, but generally only cardiomyopathy in females. Three cases (index case, his sister and her son) are described in a family with at least two other affected members. The index case underwent a successful heart transplant. The sister has cardiac involvement, myopathic changes and mental impairment--to our knowledge the first report of multisystem involvement in a female. We propose that skeletal muscle should be examined in young patients with hypertrophic cardiomyopathy. Furthermore, female relatives of males with the disease should be investigated for cardiomyopathy; they would be excellent candidates for life-saving heart transplant, since myopathy and mental retardation, if clinically evident, are mild.

Significance of pericardial effusion after heart transplantation.

The aim of this study was to evaluate the clinical significance of pericardial effusion after heart transplantation and to assess its correlation with acute rejection. One hundred fifty transplanted patients were followed up for the first year: serial echocardiographic studies were performed on the same day as were the endomyocardial biopsies; hemodynamic studies and coronary angiographies were performed 1 year after transplant. Ten days after surgery, pericardial effusion was absent in 77 patients, small in 52, moderate in 14, and large in 7, and was significantly related to severe postoperative bleeding (p < 0.001). Patients were classified according to the presence and the course of pericardial effusion in group A (absence or disappearance of previous pericardial effusion within 1 month, 107 patients) and in group B (onset, persistence, or increase in pericardial effusion, 43 patients). One hundred nineteen patients experienced > or = 1 acute rejection episode. The evolution of pericardial effusion was different (p < 0.0001) according to the number of acute rejection episodes and biopsy specimens showing acute rejection, histologic grading and time of the first episode, and histologic grading of the most severe acute rejection episode. Furthermore, there was a significant correlation with the cumulative duration of acute rejection episodes (p < 0.005) and the presence of previous cardiac surgical history (p < 0.007), but no correlation with cardiac transplant vasculopathy or with a positive weight mismatch. This study suggests that pericardial effusion in transplant recipients is associated with a higher incidence and more severe histologic grading of acute rejection episodes; its presence indicates the need for stricter monitoring of acute rejection.

Implantable left ventricular assist systems (LVAS): recent results. A report from a series of meetings sponsored by the Study Group on Advanced Heart Failure of the Working Group on Heart Failure.

Implantable left ventricular assist systems (LVAS) consist of implantable pumps with small control consoles and power sources that can be worn externally. These systems provide far greater patient mobility and independence than external pumps with bulky control consoles. Patients with implantable LVAS can be discharged from hospital and are able to return to work and resume active sports. Most patients have received these systems as a bridge to heart transplantation. Clinical status and quality of life improve dramatically after device implantation and survival on support (60-70% after approx. 100 days of support) is acceptable compared with transplant candidates on medical therapy. Patient selection and adverse events, primarily bleeding, thromboembolism and infection, are important issues with LVAS. In the future, long-term support and bridging to myocardial recovery may become important indications for LVAS.

Posttransplantation cutaneous B-cell lymphoma with monoclonal Epstein-Barr virus infection, responding to acyclovir and reduction in immunosuppression.

Posttransplantation lymphoproliferative disorders (PTLDs) represent an important complication of solid organ transplantation. The main causative factor of PTLDs seems to be the intensity and type of immunosuppressive therapy and the frequent occurrence of Epstein-Barr virus infection. PTLDs that are disseminated at diagnosis or present late after transplantation generally share an unfavorable prognosis and are unlikely to regress in response to reduction in immunosuppressive therapy. We describe a case of cutaneous B-cell lymphoma occurring 4 years after heart transplantation in which molecular analysis revealed a monoclonal pattern of Epstein-Barr virus infection and immunoglobulin gene rearrangement. In spite of its monoclonal nature and late occurrence, the lymphomatous lesions regressed completely after antiviral treatment and a reduction in immunosuppressive therapy.

Prognostic value of pulmonary hypertension in patients with chronic interstitial lung disease referred for lung or heart-lung transplantation.

BACKGROUND: The purpose of this study was to identify precise and reliable prognostic parameters in patients affected by serious chronic interstitial lung disease, who were undergoing screening for lung or heart-lung transplantation. METHODS: Hemodynamic and respiratory function parameters of 67 patients (43 with idiopathic pulmonary fibrosis, 18 with histiocytosis X, and 6 with lymphangioleiomyomatosis) undergoing clinical screening for lung transplantation. RESULTS: Statistical analysis showed that hemodynamic and respiratory function parameters in patients affected by histiocytosis X and idiopathic pulmonary fibrosis were not related to survival time. Moreover, the degree of pulmonary hypertension showed no correlation between respiratory function parameters in all the groups of diseases examined. Patients affected with histiocytosis X, even with higher degrees of pulmonary hypertension, had a better survival rate (p < 0.0005) compared with patients with idiopathic pulmonary fibrosis. CONCLUSIONS: Hemodynamic and respiratory parameters obtained during the clinical screening for lung transplantation do not predict survival and cannot be used as prognostic indicators.

Restrictive criteria for heart transplantation candidacy maximize survival of patients with advanced heart failure.

BACKGROUND: The shortage of organ donors and the amelioration of medical management of advanced heart failure mandate strict selection of heart transplant candidates on the basis of the need and probability of success of transplantation, with the aim of maximizing survival of patients with advanced heart failure, both with and without transplantation. This study analyzes the impact of restricting the criteria for heart transplantation candidacy on the outcome of patients with advanced heart failure referred for transplantation. METHODS: Survival and freedom from major cardiac events (death, resuscitated cardiac arrest, transplantation while supported with inotropes or mechanical devices) were compared between patients listed during 1990 to 1991, when standard criteria were applied (group 1, n = 118), and patients listed during 1993 to 1994, when only patients requiring continuous/recurrent intravenous inotrope therapy in spite of optimized oral medications and outpatients showing actual progression of the disease were admitted to the waiting list (group 2, n = 88). Survival and freedom from cardiac events (defined as above plus listing in urgent status) were also calculated in stable outpatients evaluated in 1993 to 1994, who were potential heart transplant candidates according to standard criteria but were not listed because of restrictive criteria (group 3, n = 52, New York Heart Association functional class > or = III, mean echocardiographic ejection fraction 0.22 +/- 0.05, mean peak oxygen consumption 12.3 +/- 1.5 ml/kg/min, mean follow-up 19 +/- 10 months). RESULTS: Thirty-one percent, 40%, and 50% of group 1 patients versus 58%, 65%, and 77% of group 2 patients underwent transplantation within 3, 6, and 12 months after listing (p < 0.0007). The 1- and 2-year survival rates after listing were 80% and 71% in group 1 versus 85% and 84% in group 2 (p < 0.0001). Freedom from death/urgent transplantation was lower in group 2 than in group 1 (55% and 48% versus 72% and 59% at 6 and 12 months, respectively; p < 0.0001). In patients undergoing transplantation, the postoperative survival rate was similar (87% and 91% at 2 years in group 1 and group 2, respectively). Two years after heart transplantation candidacy was denied, 86% of group 3 patients were alive, and 74% were event-free. CONCLUSIONS: Restricting the admissions to the waiting list to patients with refractory/progressive heart failure improved survival rates after listing by increasing the probability to undergo transplantation in a short time. Selection of most severely ill candidates did not affect postoperative survival. Survival and freedom from cardiac events were good in patients with advanced but stable heart failure, in spite of their severe functional limitation. Thus restrictive criteria for heart transplantation candidacy allows maximal survival benefit from both medical therapy and transplantation.

A semiquantitative approach to the evaluation of acute cardiac allograft rejection at endomyocardial biopsy.

BACKGROUND: Histopathologic criteria for grading of acute cardiac allograft rejection are focused on the most severe lesion that is recognized among the myocardial fragments provided by each endomyocardial biopsy specimen. Considering the distribution of rejection lesions among all the fragments improved the accuracy in characterizing the severity of rejection in pathologic studies. This study was undertaken to verify the usefulness of a semiquantitative evaluation of endomyocardial biopsy specimens, consisting of the calculation of the proportion of fragments showing rejection in the clinical setting. METHODS: Of the 2386 biopsy specimens obtained during the first posttransplantation year in 168 consecutive cardiac allograft recipients, 290 biopsy specimens constituted by > or = 3 adequate fragments and showing rejection not followed by treatment (n = 159) or being the first biopsy specimen prompting treatment with augmented immunosuppression for that rejection episode (n = 131) were selected. These biopsy specimens (index biopsy specimens) were grouped according to whether rejection was present in < or = 33%, > 33% to < or = 67%, and > 67% of the fragments. The rejection grade (according to the standardized grading system) and the proportion of fragments positive for rejection were correlated with the occurrence of clinical symptoms and signs of rejection at index biopsy and with the results of the next biopsy. RESULTS: Rejections graded > or = 3A were more frequently symptomatic (36% vs 9% for those graded < 3, p < 0.0001), as were those involving increasing proportions of fragments (< or = 33%: 5 of 124, 4%; > 33 to < or = 67%: 13 of 99, 13%; > 67%: 19 of 67, 28% [p < 0.0001]). Spontaneous resolution after untreated biopsies was more frequent in focal (grade 1A and 2) than in diffuse mild (1B) rejections (68% vs 38% [p < 0.04]), whereas progression to grade 3A or greater was less frequent (4% vs 27% [p < 0.01]). Increasing proportions of positive fragments were associated with lower frequencies of spontaneous resolution (p < 0.05) and higher frequencies of worsening (9%, 22%, 43% [p < 0.009]) or progression to grade 3A or greater (2%, 6%, 28% [p < 0.005]). Complete resolution after treatment was less frequent for increasing proportions of positive fragments at index biopsy (80%, 66%, 49% [p < 0.05]). CONCLUSIONS: Diffuse versus focal rejection pattern and the proportion of positive fragments seem to be clinically relevant in terms of occurrence of symptoms, spontaneous evolution, and response to treatment.

Prognostic indices in heart transplant candidates after the first hospitalization triggered by the need for intravenous pharmacologic circulatory support.

BACKGROUND: Patients with heart failure refractory to optimal oral pharmacologic therapy have a dismal short term prognosis. Heart transplantation is the only therapy shown to improve survival in these patients. Unfortunately, due to the critical shortage of donor organs, approximately 30% of listed patients with end-stage heart failure die before a suitable donor heart becomes available. The principal aim of this study was to determine whether intravenous pharmacologic circulatory support favorably influences the clinical course of heart transplant candidates or whether mechanical circulatory support should be instituted in this high risk patient population. METHODS: Data from 154 consecutive hospitalizations in 125 patients 49+/-12 years were retrospectively reviewed. The product limit method was used to estimate survival. Multiple logistic regression analysis was used to identify the clinical and hemodynamic variables that independently predict outcome after each admission in which heart transplantation did not occur. RESULTS: One year survival for the study population was 65%. This survival is significantly lower than the 91% 1 year survival in similarly ill patients undergoing heart transplantation. The Cox proportional hazard method identified serum bilirubin, blood urea nitrogen (BUN), serum sodium levels and right atrial pressure as independent prognostic indices. Serum bilirubin, BUN levels and duration of intravenous pharmacologic circulatory support were associated with a poor outcome. A composite index including serum bilirubin and BUN levels predicted outcome with a sensitivity and specificity of 79% and 77%, respectively. The addition of pharmacologic support duration increased the model's sensitivity to 95%, but did not significantly alter specificity that was 74%. Of the 125 patients hospitalized due to the need to initiate intravenous pharmacologic support for the first time (index hospitalization), 69 (55%) were discharged after optimization of medical therapy. Of 21 patients who did not undergo transplantation during the follow-up period, 18 (86%) died within 2 years of the index hospitalization. The duration of intravenous pharmacologic support beyond which prognosis dramatically worsens without heart transplantation is 21 days. CONCLUSION: Heart transplant candidates who require intravenous pharmacologic circulatory support for more than 21 days and do not receive a suitable donor heart within this period of time have a high mortality. Alternative therapies, such as implantation of a mechanical circulatory assist device should be considered in this high risk population.

Cardiac transplantation in Becker muscular dystrophy.

A 23-year-old man with X-linked Becker type muscular dystrophy underwent cardiac transplantation because of dilated cardiomyopathy which was complicated by terminal heart failure. Impairment of muscle function was mild and slowly progressive, whereas the cardiac disease was severe and rapidly progressive. All four chambers of the removed heart were grossly dilated; microscopically, the myocardial fibres were hypertrophic and pale; the nuclei exhibited pleomorphism with variability in nuclear size, shape, and depth of staining.

The European experience of Novacor left ventricular assist (LVAS) therapy as a bridge to transplant: a retrospective multi-centre study.

OBJECTIVE: Artificial heart devices have suffered from a negative press based on the early Jarvik experience of the 1980s. This is in stark contrast to realities of current left ventricular assist (LVAS) therapy. The Novacor N100 PC wearable left ventricular assist system (LVAS) was introduced in Europe in late 1993. This system allows implanted recipients to be completely autonomous with the system controlled by a small computer and powered by rechargeable batteries. This report represents the initial European experience with the Novacor LVAS. METHODS: Since the system was introduced with regulatory approval as a commercial product, clinicians were not bound by the constraints of a study protocol and only minimal data were collected. This report presents the results of a retrospective study of 118 consecutive patients who had the LVAS implanted as a bridge to transplant, in 19 centres over the three year period ending in November 1996. RESULTS: Mortality and morbidity varied widely between centres. The median implant time was 115 days (0-585 days) and 33% of patients returned home, supported by the LVAS. The overall survival on LVAS was 64%. The major causes of death were infection (14%) and MOF (6%). There were no significant device or system failures despite a cumulative patient experience of 24.8 years outside of a hospital environment. Patient selection and management varied greatly between centres and this was reflected in disparate outcomes. CONCLUSIONS: Optimal selection and management of LVAS patients has still to be established. While the data available for this report lacked the detail necessary to demonstrate direct causal relationships between selection and management, it was clear from the inter-centre differences that these two factors have a major impact on outcomes. This early experience has directed attention towards improved management regimes. Given the results obtained from the best centres and the ability to discharge patients to lead near-normal lives in the community, the authors believe that the Novacor LVAS now offers a real therapeutic alternative for selected end-stage heart failure patients for whom a donor heart is unavailable or who are unsuitable for transplantation.

Selection and evaluation of recipients for heart-lung and lung transplantation: the Niguarda Hospital experience.

Between January 1989 and February 1993, 52 patients were evaluated at Niguarda Hospital for lung or heart and lung transplantation. Of the 35 that entered the waiting list, a total of 19 were transplanted (14 at other institutes before our surgical programme became operative, and 5 at our hospital). Recipient selection and evaluation criteria, and timing of transplantation in the different diseases are discussed.

[Treatment with beta blockers in advanced heart failure]. / Il trattamento con betabloccanti nello scompenso cardiaco avanzato.

Sympathetic activation plays an important role in the progression of heart failure, and beta-blocker treatment not only improves ventricular function but may also slow and reverse heart remodeling. Patients with severe heart failure remain markedly symptomatic and have a poor prognosis despite optimal pharmacological treatment which includes an ACE-inhibitor. In these patients the tolerability of beta-blockers is reduced, but they could have the most to gain from this therapy, since they are more likely to show symptomatic and survival improvement in the long term. With close clinical observation during the initiation and titration of the drug, and an adequate adjustment of associated therapy, beta-blockers are tolerated in the majority of such patients. This article reviews the clinical experience of beta-blocker use in advanced heart failure, and discusses the appropriate modality of drug initiation and titration. Considerations are also made about the usefulness of prognostic parameters in the evaluation of tolerability and efficacy of beta-blocker treatment.

[Arrhythmia risk stratification in patients with heart failure according to drug treatment and its effects]. / Stratificazione del rischio aritmico nei pazienti con scompenso cardiaco in base al trattamento farmacologico ed ai suoi effetti.

Despite therapeutic advances in heart failure treatment, this syndrome still presents a poor prognosis, with a relevant mortality due to both systolic dysfunction progression and sudden death. Sudden cardiac death appears to be relatively more frequent in less compromised patients (NYHA functional class I) but in absolute numbers it is more frequent in more functionally compromised patients. The ability to predict sudden cardiac events with current available tests is poor, with the possible exception of electrophysiological test in ischemic cardiomyopathy. The risk of sudden death is proven to be increased in more advanced cardiac dysfunction and frequently the acute event can be precipitated by ischemia. Therefore the best approach in the prevention of sudden cardiac death may well be the proper treatment of ischemia and cardiac dysfunction. Beta-blockers have demonstrated a favorable effect in the prevention of sudden cardiac death. ACE-inhibitors can significantly reduce global death in heart failure patients, but their impact on sudden death appears to be limited. The same may be true for angiotensin II blockers. Diuretics have generally been demonstrated to increase sudden death, possibly via electrolyte imbalance; this may explain why spironolactone has a pronounced impact in reducing sudden death. Inotropes, in spite of their good effect on refractory heart failure and their usefulness in the compassionate care of terminally ill heart failure patients, have demonstrated an increase in sudden cardiac death. The same holds true for digoxin, in spite of its ability to reduce death due to heart failure deterioration. Antiarrhythmic drugs, with the possible exception of amiodarone, have demonstrated an unfavorable effect on sudden death incidence.

Central and peripheral haemodynamic determinants of effort tolerance in patients with heart failure.

We studied central and peripheral hemodynamics and exercise tolerance in 24 patients with left ventricular dysfunction. All were in NYHA class II or III, and echocardiographic left ventricular ejection fraction was < 35% without pharmacologic influences. Patients underwent to treadmill test (Naughton protocol), cardiopulmonary upright bicycle test, and supine bicycle test with haemodynamic measurements. All tests were exhaustive. Average exercise time was 9 +/- 3.4 min, (range 3-20). Average ejection fraction (.28 +/- 0.65) dis not correlate with working capacity (r = .32), nor did left ventricular filling pressure (pulmonary capillary wedge pressure) at rest and at peak exercise (r = .29 and r = .02). Stroke volume and stroke volume index were on average depressed, with no variations during work; cardiac output and cardiac index were also depressed, with a significant increase at peak exercise (both p < .001). Systemic and pulmonary resistances were increased, but systemic resistances tended to decrease during effort (p < .001), while pulmonary resistances did not (p = NS). We subdivided patients according to systemic vascular resistances lower or higher than 1500 dynes.cm.sec-5 at rest; this identifies two different working capacities (low systemic vascular resistances 11.7 +/- 4.4 min, high systemic vascular resistances 6.9 +/- 3.2 min, p < .05). Patients were then divided in two groups: group I (rest stroke volume > 60 ml) and group II (rest stroke volume < 60 ml). Group I worked 11 +/- 5 min, group II 8.5 +/- 3 min (p < .05). We performed a linear regression analysis between cardiac output and systemic vascular resistances at rest and during exercise in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)