[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.

[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.

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.

Congestive heart failure induced by recipient atrial tachycardia conducted to the donor atrium after orthotopic heart transplantation: complete regression after successful radiofrequency ablation.

We describe the case of a 30-year-old female patient who developed an interatrial tachycardia from the recipient to the donor atrium associated with signs of congestive heart failure 5 years after orthotopic heart transplantation. The patient underwent catheter mapping followed by successful radiofrequency (RF) ablation at the site of the presumed electrical connection between the recipient and the donor atria, through the interatrial surgical suture line, with stable recovery of sinus rhythm and disappearance of signs of left ventricular dysfunction. RF catheter ablation is confirmed to be feasible and safe in the treatment of heart transplant patients even in the presence of rare forms of arrhythmias, thus offering a cure for tachycardia to these patients.

Outpatient intermittent dobutamine therapy in congestive heart failure.

BACKGROUND: Patients with severe heart failure often progress to the condition where oral agents alone are inadequate to maintain a clinically compensated state. The use of outpatient intravenous inotropic therapy is contentious because it may hasten the progression of the underlying disease or aggravate existing ventricular dysrhythmia. We describe the clinical outcome of 40 pts with severe congestive heart failure (CHF) treated with outpatient dobutamine (D) Therapy. METHODS: Outpatient inotropic therapy with D was started in 40 pts (36 males, 4 females, mean age 56.3±9 years) with chronic CHF and persistence of severe symptoms despite maximal oral therapy. All the pts had required hospitalization with need for i.v. inotropic therapy during the previous 6 months (mean hospital stay 41±28 days).At baseline 35 pts were in NYHA class IV, 5 in class III, mean echo LVEF was 23±5%, cardiac index 1.8±0.4l/min/m(2), pulmonary capillary wedge pressure 22±9.4 mmHg. 18 pts were listed for heart transplantation (HTx). D was infused with portable pumps via permanent i.v. catheters and the mean dose was 3.0±0.83µg/kg/min (range 2-5). The duration of home infusion period was 60±30h/week (range 24-168). RESULTS: During follow-up (mean 393±482 days, range 10-2182) NYHA class improved (III=32-=8). There were 19 hospitalizations in 14 pts (mean hospital stay 12.7±4 days). All the listed pts underwent HTx with 1 intrahospital death, 1 late death (1591 days for lung cancer) and 16 long-term survivors (mean post-operation follow-up 936±215 days). Fourteen not listed pts died after prolonged support (580±252 days - 13 for irreversible HF, accounting for the majority of rehospitalizations and 1 suddenly while not on D infusion). One pt developed non-fatal SVT during D infusion. There were no mechanical or infectious complications related to the device. CONCLUSIONS: Low-dose outpatient D therapy improved NYHA class and decreased hospitalization in pts with refractory CHF without major deleterious effects that may impact adversely on survival on the waiting list.

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.

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.

Arrhythmias in sport.

The presence of arrhythmias in athletes is not infrequent. Bradyarrhythmias are more frequent in sportsmen than in the general population. This fact is often due to a 'relative vagal hypertony', owing to a training effect. Tachyarrhythmias are also present in sportsmen in almost the same percentage as in sedentary people. Any of several types of tachyarrhythmia can be seen. Abnormal heart conditions can be demonstrated in many athletes with symptomatic tachyarrhythmias. These arrhythmias frequently occur during exercise and in the early phase of recovery. An organic disorder was present in 26 of 32 athletes who were investigated with an exercise test, Holter monitoring and an electrophysiological test because of the presence of tachyarrhythmias. In six cases we were not able to find any cardiac disease. In 75% of these cases the arrhythmias had a strong relation with exercise. During follow-up (1-5 years; mean 2.88 years) some arrhythmias recurred in spite of medical treatment, in 12 of the 32 subjects, while the other 20 were free of symptoms and arrhythmias. In our opinion it is not possible to ascribe to sport, per se, the direct responsibility for these arrhythmias.

[Clinico-diagnostic significance of the determination of bile acids in chronic liver diseases]. / Significato clinico-diagnostico del dosaggio di alcuni acidi biliari sierici nelle epatopatie croniche.

Certain conjugated biliary acids (total pool - choliglycine - sulpholytic choliglycine) and the following haematochemical parameters: total bilirubin and its direct quota, alkaline phosphatase, albumin, prothrombin activity, gamma globulin, oxalacetic and pyruvic transaminase were radioimmunologically (RIA) studied in 115 subjects. Subjects were divided into the following subgroups: --20 normal controls; --20 cases of persistent chronic hepatitis; --20 cases of active chronic hepatitis; --15 cases of A.C.H. with cirrhosis; --20 cases of cirrhosis without direct hyperbilirubinaemia; --20 cases of cirrhosis with direct hyperbilirubinaemia. Each case was assigned to its particular group on the basis of the histological report on each patient. The following observations were drawn from the results obtained: --there is a progressive increase in above normal biliary acid rate in proportion to the gravity of the liver pathology; --choliglycine especially and to a lesser extent the total pool increased sufficiently to distinguish between normal and hepatopathic subjects (PCH and ACH) and also between PCH and ACH patients; --the combination of cirrhosis and ACH causes a significant increase in total pool and chliglycine over levels noted in ACH alone; --in contrast no difference is found between the levels of these acids in inactive (or minimally active) cirrhosis and ACH with cirrhosis; --gamma globulin, oxalacetic and pyruvic transaminase levels were found to have substantially the same diagnostic significance as choliglycine in the early stages of liver diseases. Significant correlations were also encountered between total conjugated biliary acid pool and choliglycine (not in the group with cirrhosis without direct hyperbilirubinaemia) and between total pool and choliglycine with haematochemical cholestasis test results (alkaline phosphatase and total and direct bilirubin) the latter only in the two cirrhotics groups. In conclusion, choliglycine was found to be the most sensitive of the biliary acids routinely measured by RIA and is valuable in clinical practice not as a substitute for the main liver tests but as an extremely useful and sensitive addition to them. In clinical practice, its use is recommended in the diagnosis and monitoring of healthy subjects at risk and those with chronic liver conditions (PCH, ACH, ACH + C).