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Effects of carvedilol, a vasodilator-beta-blocker, in patients with congestive heart failure due to ischemic heart disease. Australia-New Zealand Heart Failure Research Collaborative Group.

BACKGROUND: beta-Blocker therapy has been shown to increase ejection fraction in patients with heart failure of idiopathic etiology. However, in patients with heart failure of ischemic etiology, the effects of this treatment on left ventricular function remain uncertain, as do the effects on exercise performance and symptoms. METHODS AND RESULTS: This study investigated the effects of carvedilol, a beta-blocker with alpha 1-blocking properties, on left ventricular size and function, maximal and submaximal exercise performance, and symptoms in 415 patients with stable heart failure of ischemic etiology (ejection fraction < 45%). After a 2- to 3-week run-in phase on open-label low-dose carvedilol, patients were randomized to continued treatment with carvedilol (up to 25 mg BID) or to matching placebo. After 6 months, left ventricular ejection fraction measured by radionuclide ventriculography had increased by 5.2% (2P < .0001) in the carvedilol group compared with the placebo group, and left ventricular end-systolic and end-diastolic dimensions measured by two-dimensionally guided M-mode echocardiography had decreased by 2.6 mm (2P = .0005) and 1.3 mm (2P = .05), respectively. There were no significant changes in either treadmill exercise duration or 6-minute walk distance between carvedilol and placebo groups (both 2P > .1); in the carvedilol group, exercise performance was therefore maintained with a 23% lower rate-pressure product. Symptoms assessed by the New York Heart Association (NYHA) scale and the Specific Activity Scale (SAS) were unchanged in two thirds of patients in both groups, but there was a small excess of patients whose symptoms worsened and a deficit of patients whose symptoms improved among those assigned carvedilol (NYHA, 2P = .05; SAS, 2P = .02). CONCLUSIONS: In patients with heart failure of ischemic etiology, 6-month treatment with carvedilol improved left ventricular function and maintained exercise performance at a lower rate-pressure product, but symptoms assessed by functional class were slightly worsened. A larger-scale trial is now required to determine whether this treatment will reduce serious morbidity and mortality from heart failure.

Adrenergic beta-Antagonists↗

[Spanish Heart Transplantation Registry. 17th official report of the Spanish Society of Cardiology Working Group on Heart Failure, Heart Transplantation, and Associated Therapies (1984-2005)].

INTRODUCTION AND METHODS: This article summarizes the general characteristics of heart transplantation in Spain and the results achieved, once data for 2005 have been included. RESULTS: In the course of the last year, 287 heart transplantations were performed, which brings the total to 4967 since 1984. Clinically, the typical Spanish heart transplant patient is male, aged about 50 years, has blood group A or O, has non-revascularizable coronary disease or idiopathic dilated cardiomyopathy, and is in New York Heart Association functional class IV/IV. The percentage of emergency heart transplants carried out was 22%, which is considerably lower than in the previous year (i.e., 35%) and slightly lower than the average for the last 5 years (i.e., 23%). The early mortality rate was 10%, which is similar to that in the previous year and lower than the average for the last 5 years (i.e., 12%). After adding the 2005 results to those of previous years, the survival probabilities at 1, 5, and 10 years were 75%, 65%, and 50%, respectively. On calculating survival curves for separate historical periods, a significant improvement could be seen for the last 5 years, in which the 1- and 5-year survival probabilities were 80% and 70%, respectively. The most frequent cause of death in the first month was acute graft failure; in the first year, infection and rejection were most common; and, in the long term, tumors and the combination of graft vascular disease with sudden death. CONCLUSIONS: Comparative analysis of survival rates showed that short-, medium-and long-term outcomes in Spain are consistent with those reported in the world literature, including a continuing trend towards better survival over the years.

Cause of Death↗

Analysis of the heart antigens. Homologous and heterologous anti-heart antibodies and analysis of the heart specific antigens.

The present study has indicated the presence of 3 heart specific antigens, using homologous and heterologous antibodies produced in immunized rabbits. Two of these antigenic proteins exhibit restricted organ specificity for heart and the other one shares by heart and kidney. One of these 2 heart specific antigens reacts to both homologous and heterologous anti-heart sera absorbed with kidney, while the other reacts to only heterologous anti-heart sera. The former has an electrophoretic mobility corresponding to that of serum beta-globulin, and is found to have a molecular weight of about 175,000. The latter has the same electrophoretic mobility as that of alpha2-globulin and is found to have a molecular weight of about 50,000.

Animals↗

[Comparison of the effects of regional ischemia and of reperfusion on the hypertrophied heart of spontaneously hypertensive rats and the heart of Wistar-Kyoto rats with isolated perfused heart via the left atrium. Effects of lidocaine, propranolol and verapamil].

1. A comparative study between the effects of ischemia and reperfusion on the hypertrophied heart of spontaneously hypertensive rat (SHR) and on the heart of Wistar-Kyoto (WKY) was carried out in working heart conditions. 2. The decrease of coronary flow induced by a coronary occlusion had an equal magnitude in the two groups. In the SHR group, the aortic output became null in 40% of the cases, whereas this effect was never seen in WKY group. 3. In reperfusion conditions, the recovery of haemodynamic values was slower in SHR group. The release of LDH and the rhythmic disturbances were also increased. 4. The perfusion of SHR hearts by lidocaine (4.3 10(-5) M), propranolol (7.7 10(-6) M) and verapamil (1.1 10(-7) M) decreased significantly the heart rate and the aortic output. 5. When these substances were added to the perfusion medium, the deleterious effects of reperfusion were greatly reduced. Aortic output recovered more quickly than his basal values and the enzymatic leakage was decreased. None of the hearts fibrillated after lidocaine and propranolol. Ventricular fibrillation continued in 14% of cases after verapamil compared to 80% of cases in the control group.

Animals↗

Cardiac resynchronization therapy improves heart rate profile and heart rate variability of patients with moderate to severe heart failure.

OBJECTIVES: This study sought to report long-term changes of cardiac autonomic control by continuous, device-based monitoring of the standard deviation of the averages of intrinsic intervals in the 288 five-min segments of a day (SDANN) and of heart rate (HR) profile in heart failure (HF) patients treated with cardiac resynchronization therapy (CRT). BACKGROUND: Data on long-term changes of time-domain parameters of heart rate variability (HRV) and of HR in highly symptomatic HF patients treated with CRT are lacking. METHODS: Stored data were retrieved for 113 HF patients (New York Heart Association functional class III to IV, left ventricular ejection fraction < or =35%, QRS >120 ms) receiving a CRT device capable of continuous assessment of HRV and HR profile. RESULTS: The CRT induced a reduction of minimum HR (from 63 +/- 9 beats/min to 58 +/- 7 beats/min, p < 0.001) and mean HR (from 76 +/- 10 beats/min to 72 +/- 8 beats/min, p < 0.01) and an increase of SDANN (from 69 +/- 23 ms to 93 +/- 27 ms, p < 0.001) at three-month follow-up, which were consistent with improvement of functional capacity and structural changes. Different kinetics were observed among these parameters. The SDANN reached the plateau before minimum HR, and mean HR was the slowest parameter to change. Suboptimal left ventricular lead position was associated with no significant functional and structural improvement as well as no change or even worsening of HRV. The two-year event-free survival rate was significantly lower (62% vs. 94%, p < 0.005) in patients without any SDANN change (Delta change < or =0%) compared with patients who showed an increase in SDANN (Delta change >0%) four weeks after CRT initiation. CONCLUSIONS: Cardiac resynchronization therapy is able to significantly modify the sympathetic-parasympathetic interaction to the heart, as defined by HR profile and HRV. Lack of HRV improvement four weeks after CRT identifies patients at higher risk for major cardiovascular events.

Female↗

Heart substitution: transplantation and total artificial heart. The Texas Heart Institute experience.

Two methods of heart substitution have been used at the Texas Heart Institute: cardiac transplantation and the total artificial heart (TAH). Cardiac transplantation is an effective means of saving patients with endstage heart disease and, since the introduction of the immunosuppressive agent cyclosporine, survival has increased significantly. In a recent series from July 1982 to May 1984, 25 patients underwent cardiac transplantation at the Texas Heart Institute. Nineteen of these patients are alive, in Functional Class I, and leading normal lives. A major disadvantage of cardiac transplantation is that it cannot be used on an emergency basis for postcardiotomy patients. In this situation, TAH has been used twice (1969 and 1981) as the first stage to maintain circulation prior to subsequent cardiac transplantation. In both instances, the TAH functioned well until a satisfactory donor was found. This demonstrates the feasibility of the two-staged concept and encourages further development of cardiac prostheses.

Adult↗

Association of cystatin C with mortality, cardiovascular events, and incident heart failure among persons with coronary heart disease: data from the Heart and Soul Study.

BACKGROUND: Serum creatinine and related estimating equations predict cardiovascular events and mortality among persons with coronary heart disease (CHD). Cystatin C is a novel and sensitive endogenous marker of kidney function. Whether cystatin C concentrations are associated with adverse events among ambulatory persons with CHD is unknown. METHODS AND RESULTS: Nine hundred ninety ambulatory persons with CHD were categorized into quartiles of serum cystatin C at inception, with < or = 0.91 mg/L constituting the lowest quartile (I) and > or = 1.30 mg/L constituting the highest (IV). Cox proportional hazards models evaluated time to all-cause mortality, cardiovascular events (composite of CHD death, myocardial infarction, and stroke), and incident heart failure. After a median follow-up of 37 months, 132 participants (13%) died, 101 (10%) had cardiovascular events, and 57 (7%) had incident heart failure. Compared with participants in the lowest cystatin C quartile, those in the highest quartile were at increased risk of all-cause mortality (hazard ratio, 3.6; 95% CI, 1.8 to 7.0), cardiovascular events (hazard ratio, 2.0; 95% CI, 1.0 to 3.8), and incident heart failure (hazard ratio, 2.6; 95% CI, 1.0 to 6.9) in analyses adjusted for traditional cardiovascular risk factors. Cystatin C in the highest quartile predicted similar risk for these outcomes among participants with lower (< or = 60 mL/min per 1.73 m2) or higher estimated glomerular filtration rate and among participants with or without microalbuminuria. CONCLUSIONS: High cystatin C concentrations predict substantial increased risks of all-cause mortality, cardiovascular events, and incident heart failure among ambulatory persons with CHD. This risk is not completely captured by measures of kidney function routinely used in clinical practice.

Aged↗

Pathology of cardiac transplantation: recipient hearts (chronic heart failure) and donor hearts (acute and chronic rejection).

Pathologic examination of both the recipient and the donor heart is critical to the success of cardiac transplantation. Idiopathic dilated cardiomyopathy and end-stage ischemic heart disease are still the most common diagnoses for which cardiac transplantation is performed in the United States. After transplantation, the donor heart is susceptible to immunologic (acute and chronic rejection), infectious, and ischemic injury. Other long-term changes, such as hypertrophy of the myocytes and interstitial fibrosis, may also affect the function of the transplanted heart. Periodic endomyocardial biopsies are important for monitoring the status of the transplanted heart. In patients treated with cyclosporine, the clinical signs of rejection may be minimal, and routine biopsy is the only means of detecting early rejection.

Acute Disease↗

Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group.

BACKGROUND: Heart failure in blacks has been associated with a poorer prognosis than in whites. In such diseases as hypertension, blacks show pathophysiological differences and respond differently to some therapies than whites. The aim of this study is to evaluate the clinical characteristics and response to therapy of black compared with white patients with heart failure. METHODS AND RESULTS: In the first Vasodilator-Heart Failure Trial (V-HeFT I), 180 black male patients were compared with 450 white male patients for baseline characteristics, prognosis, and response to therapy. In V-HeFT II, the same comparisons were made for 215 black and 574 white male patients, including an analysis stratified by the presence or absence of a history of hypertension. In both trials, black patients had a lower incidence of coronary artery disease, greater incidence of previous hypertension, and a greater cardiothoracic ratio (P < .05) than white patients. In V-HeFT II, plasma norepinephrine levels were significantly less in blacks; plasma renin activity was less only in blacks with a history of hypertension. Overall mortality or hospitalization for congestive heart failure did not differ between blacks and whites in the placebo group in V-HeFT I. However, the mortality of black patients receiving hydralazine plus isosorbide dinitrate (H-I) was reduced (P = .04) in V-HeFT I, whereas white patients showed no difference from placebo. In V-HeFT II, only white patients showed a mortality reduction from enalapril therapy compared with H-I therapy (P = .02). Whites also showed evidence of greater blood pressure reduction and enhanced regression of cardiac size in response to enalapril. When stratified by history of hypertension in V-HeFT II, only whites with a history of hypertension, who had greater renin levels, showed significant mortality reduction with enalapril compared with H-I therapy. Hospitalization rates did not differ between treatment groups in either study. CONCLUSION: Whites and blacks showed differences in cause, neurohormonal stimulation, and pharmacological response in heart failure. This retrospective analysis suggests angiotensin-converting enzyme inhibitors are particularly effective in whites, and the H-I combination can be equally effective in blacks. Prospective trials involving large numbers of black patients are needed to further clarify their response to therapy.

Angiotensin-Converting Enzyme Inhibitors↗

Pretransplant rinse of hearts preserved with colloid-free UW solution and more effective heart preservation: studies in a rat abdominal heart transplant model.

BACKGROUND: University of Wisconsin solution (UW) provides effective heart preservation under hypothermic conditions, but it can be deleterious at warmer temperatures. Re-warming during the implantation of the graft may be a problem. This study examined the damaging effect of peri-operative warm ischemia in a transplant setting and recovery from such damage. The amelioration of damage by rinsing the graft before re-warming and transplantation was also examined. METHODS: Rat donor hearts were preserved for 2 hr (0 degrees C) as follows: Series A was preserved with colloid-free UW (MUW), St. Thomas' solution (ST), or calcium-supplemented MUW (MUW+Ca) followed by either transplantation or warming (22 degrees C) for 10 min before transplantation. Series B was preserved with MUW, rinsed with fresh MUW, ST, MUW+Ca, or low-potassium MUW before warming and transplantation. All heart isografts were transplanted heterotopically with an indwelling left intraventricular balloon-tipped catheter. Graft function was measured 1 and 7 days after transplantation. RESULTS: Grafts re-warmed rapidly during implantation. Function (left ventricular developed pressure, contractility, and relaxation) was significantly and persistently diminished in MUW-preserved grafts subjected to additional warming before transplantation. Preservation with ST was less effective than MUW despite being unaffected by warming. Preservation with MUW+Ca and rinsing with fresh MUW or ST before re-warming allowed recovery of function within 7 days despite significantly diminished function on day 1. CONCLUSION: This study demonstrated that an increase in the peri-transplant warm ischemic period was detrimental when hearts were preserved with MUW. Preservation with calcium-supplemented MUW or rinsing the heart with fresh MUW or ST before transplantation ameliorated this damage.

Adenosine↗

[Anthracycline-induced heart failure aggravated by pregnancy. Survival after cardiac assistance with artificial heart device and heart transplantation].

We report a case of a young woman suffering from a steady anthracycline-induced myocardiopathy with a decreased left ventricular function on echocardiography. A pregnancy was initiated, without worsening of the cardiopathy until 34 weeks. Nine days after delivery, an acute heart failure was observed leading to heart transplantation after cardiac assistance with heart cardiac device. As pregnancy is an extended stress test for a chronic failing heart, a multidisciplinary decision of pregnancy initiation and follow up should be preferred in pre and postpartum period, when such a cardiopathy exists.

Adult↗

What resting heart rate should one aim for when treating patients with heart failure with a beta-blocker? Experiences from the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF).

OBJECTIVES: The goal of this study was to explore the question: what resting heart rate (HR) should one aim for when treating patients with heart failure with a beta-blocker? BACKGROUND: The interaction of pretreatment and achieved resting HR with the risk-reducing effect of beta-blocker treatment needs further evaluation. METHODS: Cardiovascular risk and risk reduction were analyzed in five subgroups defined by quintiles (Q) of pretreatment resting HR in the Metoprolol Controlled Release/Extended Release Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). RESULTS: Mean baseline HR in the 5 Qs were 71, 76, 81, 87, and 98 beats/min; achieved HR 63, 66, 68, 72, and 75 beats/min; and net change -8, -10, -11, -13, and -14 beats/min, respectively. Baseline HR was related to a number of baseline characteristics. Cardiovascular risk was no different in Q1 to Q4 (placebo groups) but increased in Q5 (HR above 90 beats/min). No relationship was observed between the risk-reducing effect of metoprolol controlled release/extended release (CR/XL) and baseline HR in the five Qs of baseline HR, or achieved HR, or change in HR during follow-up, respectively. CONCLUSIONS: Metoprolol CR/XL significantly reduced mortality and hospitalizations independent of resting baseline HR, achieved HR, and change in HR. Achieved HR and change in HR during follow-up were closely related to baseline HR; therefore, it was not possible to answer the question posed. Instead, one has to apply a very simple rule: aim for the target beta-blocker dose used in clinical trials, and strive for the highest tolerated dose in all patients with heart failure, regardless of baseline and achieved HR.

Adrenergic beta-Antagonists↗

[Spanish Registry on Heart Transplantation. 14th official report of the working group on heart failure, heart transplantation and other therapeutic alternative of the Spanish Society of Cardiology (1984-2002)].

This report describes the general characteristics and outcomes of heart transplantation in Spain after data from 2002 were added to the registry. In 2002, 310 heart transplantations were performed. Since 1984, a total of 4,096 procedures have been performed. The average clinical profile of patients receiving a heart transplant in Spain is that of a man about 50 years old, blood group A, with nonrevascularizable coronary artery disease and functional status IV/IV (NYHA). The percentage of emergency heart transplantations was 26%, which is higher than the previous year (19%) and the mean for the preceding five years (22%). The early mortality rate was 10%, which is significantly lower than the mean for the preceding five years (14%). After combining the 2002 results with those of previous years, an increase in survival rate was seen. Thus, the probability of survival in the first, fifth and tenth years was 76%, 66%, and 54%, respectively. When survival rates for separate periods were considered, a clear improvement was seen from the first year (80%) to the fifth year (72%). The most frequent causes of death were acute graft failure in the first month, infection and rejection in the first year, and tumors and the combination of vascular disease of the graft with sudden death in the long term. Comparative analysis of survival rates shows that our long-term results are slightly better than those published worldwide, with a clear tendency for survival rate to improve as a consequence of the experience acquired in all stages of this cross-disciplinary procedure.

Heart Failure↗

The infundibular septum in normal hearts and in hearts with isolated ventricular septal defect. A comparison between Japanese and Dutch hearts.

The observation that subpulmonary or doubly committed subarterial ventricular septal defects occur with a high frequency among orientals as compared to westerners has led to the hypothesis that a racial difference exists with regard to normal and abnormal development of the embryonic conal septum. In an attempt to contribute to this concept we have studied 24 normal hearts and 70 hearts with a perimembranous ventricular septal defect from patients of Japanese and Dutch origin. The length of the infundibular septum and the length of the right ventricle were not statistically different between the 2 groups. These findings suggest that in normal hearts and in hearts with perimembranous ventricular septal defects no racial differences exist with respect to the role of the embryonic conal septum in contributing to the definitive infundibular septum. The results indicate that subpulmonary or doubly committed subarterial defects may have a different origin from that of the usual perimembranous defect.

Asian People↗

[Spanish Registry of Heart Transplantation. 15th Official Report of the Working Group on Heart Failure, Heart Transplantation and Other Therapeutic Alternatives of the Spanish Society of Cardiology (1984-2003)].

This paper outlines the general characteristics and results obtained with heart transplantation in Spain after including the data for the year 2003. In 2003, 290 heart transplants were performed. Since 1984, a total of 4386 procedures have been performed. The average clinical profile of patients receiving a heart transplant in Spain is that of a man about 50 years old, blood group A, with nonrevascularizable coronary artery disease and functional status IV/IV (NYHA). The percentage of emergency heart transplantations was 29%, which is higher than in the previous year (26%) and the mean for the preceding 5 years (20%). The early mortality rate was 13%, which is similar to the mean for the preceding 5 years (13%). After combining the 2003 results with those of the previous years, the probability of survival at 1, 5 and 10 years was 76%, 66% and 54%, respectively. When survival rates for separate periods were considered, a significant improvement was seen in the last 5 years, with survival rates at of 81% at 1 year and 74% at 5 years. The most frequent causes of death were acute graft failure in the first month, infection and rejection in the first year, and a combination of vascular disease of the graft with sudden death in the long term. Comparative analysis of survival rates shows that our long-term results are slightly better than those published in the literature, with a gradual tendency for survival rate to improve in recent years.

Adolescent↗

A randomized clinical trial of hospital-based, comprehensive cardiac rehabilitation versus usual care for patients with congestive heart failure, ischemic heart disease, or high risk of ischemic heart disease (the DANREHAB trial)--design, intervention, and population.

BACKGROUND: Current guidelines broadly recommend comprehensive cardiac rehabilitation (CR), although evidence for this is still limited. It is not known whether evidence from before 1995 is still valid. STUDY DESIGN: The DANish Cardiac ReHABilitation (DANREHAB) trial was designed as a centrally randomized clinical trial to clarify whether hospital-based comprehensive CR is superior to usual care for patients with congestive heart failure, ischemic heart disease, or high risk for ischemic heart disease. A combined primary outcome measure included total mortality, myocardial infarction, or readmissions due to heart disease based on linkage to public registries. The CR was an individually tailored, multidisciplinary program (6 weeks of intensive CR and 12 months of follow-up) including patient education, exercise training, dietary counseling, smoking cessation, psychosocial support, risk factor management, and clinical assessment. STUDY POPULATION: Of 5060 discharged patients, 1614 (32%) were eligible for the trial and 770 patients were randomized (47% of those eligible). Participants were younger (P < .001) and had less comorbidity than nonparticipants (P < .03). CONCLUSION: Our trial shows that a large-scale, centrally randomized clinical trial on comprehensive CR can be conducted among a broadly defined patient group, but reaching the stipulated number of 1800 patients was difficult. Although the study included relatively many women and older people, elderly patients and patients with high comorbidity were underrepresented, which may influence the external validity.

Adult↗