Paul Mohacsi

Effect of Carvedilol on the Morbidity of Patients With Severe Chronic Heart Failure Results of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) Study

Background—&bgr;-Blocking agents improve functional status and reduce morbidity in mild-to-moderate heart failure, but it is not known whether they produce such benefits in severe heart failure. Methods and Results—We randomly assigned 2289 patients with symptoms of heart failure at rest or on minimal exertion and with an ejection fraction <25% (but not volume-overloaded) to double-blind treatment with either placebo (n=1133) or carvedilol (n=1156) for an average of 10.4 months. Carvedilol reduced the combined risk of death or hospitalization for a cardiovascular reason by 27% (P =0.00002) and the combined risk of death or hospitalization for heart failure by 31% (P =0.000004). Patients in the carvedilol group also spent 27% fewer days in the hospital for any reason (P =0.0005) and 40% fewer days in the hospital for heart failure (P <0.0001). These differences were as a result of both a decrease in the number of hospitalizations and a shorter duration of each admission. More patients felt improved and fewer patients felt worse in the carvedilol group than in the placebo group after 6 months of maintenance therapy (P =0.0009). Carvedilol-treated patients were also less likely than placebo-treated patients to experience a serious adverse event (P =0.002), especially worsening heart failure, sudden death, cardiogenic shock, or ventricular tachycardia. Conclusion—In euvolemic patients with symptoms at rest or on minimal exertion, the addition of carvedilol to conventional therapy ameliorates the severity of heart failure and reduces the risk of clinical deterioration, hospitalization, and other serious adverse clinical events.

The 2013 International Society for Heart and Lung Transplantation Guidelines for mechanical circulatory support: Executive summary

Institutional Affiliations Co-chairs Feldman D: Minneapolis Heart Institute, Minneapolis, Minnesota, Georgia Institute of Technology and Morehouse School of Medicine; Pamboukian SV: University of Alabama at Birmingham, Birmingham, Alabama; Teuteberg JJ: University of Pittsburgh, Pittsburgh, Pennsylvania Task force chairs Birks E: University of Louisville, Louisville, Kentucky; Lietz K: Loyola University, Chicago, Maywood, Illinois; Moore SA: Massachusetts General Hospital, Boston, Massachusetts; Morgan JA: Henry Ford Hospital, Detroit, Michigan Contributing writers Arabia F: Mayo Clinic Arizona, Phoenix, Arizona; Bauman ME: University of Alberta, Alberta, Canada; Buchholz HW: University of Alberta, Stollery Children’s Hospital and Mazankowski Alberta Heart Institute, Edmonton, Alberta, Canada; Deng M: University of California at Los Angeles, Los Angeles, California; Dickstein ML: Columbia University, New York, New York; El-Banayosy A: Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania; Elliot T: Inova Fairfax, Falls Church, Virginia; Goldstein DJ: Montefiore Medical Center, New York, New York; Grady KL: Northwestern University, Chicago, Illinois; Jones K: Alfred Hospital, Melbourne, Australia; Hryniewicz K: Minneapolis Heart Institute, Minneapolis, Minnesota; John R: University of Minnesota, Minneapolis, Minnesota; Kaan A: St. Paul’s Hospital, Vancouver, British Columbia, Canada; Kusne S: Mayo Clinic Arizona, Phoenix, Arizona; Loebe M: Methodist Hospital, Houston, Texas; Massicotte P: University of Alberta, Stollery Children’s Hospital, Edmonton, Alberta, Canada; Moazami N: Minneapolis Heart Institute, Minneapolis, Minnesota; Mohacsi P: University Hospital, Bern, Switzerland; Mooney M: Sentara Norfolk, Virginia Beach, Virginia; Nelson T: Mayo Clinic Arizona, Phoenix, Arizona; Pagani F: University of Michigan, Ann Arbor, Michigan; Perry W: Integris Baptist Health Care, Oklahoma City, Oklahoma; Potapov EV: Deutsches Herzzentrum Berlin, Berlin, Germany; Rame JE: University of Pennsylvania, Philadelphia, Pennsylvania; Russell SD: Johns Hopkins, Baltimore, Maryland; Sorensen EN: University of Maryland, Baltimore, Maryland; Sun B: Minneapolis Heart Institute, Minneapolis, Minnesota; Strueber M: Hannover Medical School, Hanover, Germany Independent reviewers Mangi AA: Yale University School of Medicine, New Haven, Connecticut; Petty MG: University of Minnesota Medical Center, Fairview, Minneapolis, Minnesota; Rogers J: Duke University Medical Center, Durham, North Carolina

Palliative care in heart failure: a position statement from the palliative care workshop of the Heart Failure Association of the European Society of Cardiology

Heart failure is a serious condition and equivalent to malignant disease in terms of symptom burden and mortality. At this moment only a comparatively small number of heart failure patients receive specialist palliative care. Heart failure patients may have generic palliative care needs, such as refractory multifaceted symptoms, communication and decision making issues and the requirement for family support. The Advanced Heart Failure Study Group of the Heart Failure Association of the European Society of Cardiology organized a workshop to address the issue of palliative care in heart failure to increase awareness of the need for palliative care. Additional objectives included improving the accessibility and quality of palliative care for heart failure patients and promoting the development of heart failure‐orientated palliative care services across Europe. This document represents a synthesis of the presentations and discussion during the workshop and describes recommendations in the area of delivery of quality care to patients and families, education, treatment coordination, research and policy.

Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology.

Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition.

Prognostic impact of plasma N-terminal pro-brain natriuretic peptide in severe chronic congestive heart failure: a substudy of the Carvedilol Prospective Randomized Cumulative Survival (COPERNICUS) trial.

Background—The utility of N-terminal proBNP (NT-proBNP) to predict the occurrence of death and hospitalization was prospectively evaluated in the COPERNICUS study, which enrolled patients with an ejection fraction <25% and symptoms of chronic congestive heart failure at rest or on minimal exertion. Methods and Results—Baseline plasma concentrations of NT-proBNP were measured in a subgroup of 814 men and 197 women with symptoms at rest or on minimal exertion who were enrolled in the COPERNICUS study and were randomized to placebo (n=506) or carvedilol (n=505). Values of NT-proBNP were markedly increased despite the requirement that patients be euvolemic before the start of treatment (mean±SD, 3235±4392 pg/mL; median, 1767 pg/mL). By univariate Cox regression analysis, NT-proBNP was found to be a powerful predictor of subsequent all-cause mortality (relative risk [RR], 2.7; 95% CI, 1.7 to 4.3; P=0.0001 for above versus below median) and all-cause mortality or hospitalization for heart failure (RR, 2.4; 95% CI, 1.8 to 3.4; P=0.0001 for above versus below median). The predictive value of NT-proBNP was similar when both placebo and carvedilol patients were analyzed separately. No significant interaction was found between NT-proBNP and treatment group (P=0.93 for above- versus below-median NT-proBNP). Conclusions—NT-proBNP was consistently associated with increased risk for all-cause mortality and for all-cause mortality or hospitalization for heart failure in patients with severe congestive heart failure, even in those who were clinically euvolemic. This marker therefore may be a useful tool in risk stratification of patients with severe congestive heart failure.

Report from a consensus conference on antibody-mediated rejection in heart transplantation

BACKGROUND The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation. METHODS The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus. RESULTS A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided. CONCLUSIONS The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.

The registry of the international society for heart and lung transplantation: twentieth official adult heart transplant report—2003

Although only a small number of lung and heart– lung transplantation procedures were performed between 1963 and 1973, the current eras of heart–lung and lung transplantation, which began in 1981 and 1983, respectively, are now entering their third decades. The optimism of the considerable success of these modalities has been tempered by limitations, such as the shortage of donor organs, and by problems, such as chronic allograft dysfunction. This portion of the Twentieth Official Report summarizes the current status of adult heart–lung and lung transplantation from data submitted to the Registry from centers around the world. The Registry now contains information on more than 2000 adult heart–lung recipients and almost 14,000 adult lung recipients, and provides a robust database for analysis.

Effects of rapamycin on growth factor-stimulated vascular smooth muscle cell DNA synthesis. Inhibition of basic fibroblast growth factor and platelet-derived growth factor action and antagonism of rapamycin by FK506.

Rapamycin (RPM) is a potent and effective immuno-suppressant which we have shown previously to inhibit intimai thickening in rat allograft and balloon-injured arteries. In this report, we have examined the effects of RPM on growth factor-induced vascular smooth muscle cell (VSMC) DNA synthesis. RPM potently inhibited platelet-derived growth factor (PDGF) (IC50=5×10-9 M) and basic fibroblast growth factor (bFGF) (IC50=8×10-10 M)-induced VSMC DNA synthesis. In contrast, only the highest concentrations of FK506 and CsA significantly altered PDGF- or bFGF-induced VSMC DNA synthesis. Addition of RPM (10-9 M) at as late as 46 hr after growth factor addition still effectively suppressed bFGF- or PDGF-induced DNA synthesis by 76% and 54%, respectively. The extent of the antagonism of RPMs inhibition of bFGF-induced VSMC DNA synthesis by FK506 was inversely proportional to RPM concentration and directly proportional to FK506 concentration.

The prevalence of anemia in chronic heart failure

OBJECTIVES To assess prevalence of anemia and its correlation with NYHA-class in patients with congestive heart failure. BACKGROUND Recently, it was reported that anemia in congestive heart failure patients is common and correlated with the severity of disease. In these patients with anemia, treatment with erythropoietin and intravenous iron improved cardiac function significantly. METHODS 193 patients from a tertiary heart failure outpatient clinic (mean age 54 years) were included in a retrospective analysis. Fourteen patients were in NYHA-class I, 69 class II, 79 class III, and 31 class IV. All patients had clinical and laboratory evaluation, echocardiography and coronary angiography. Patients with secondary anemia or on hemodialysis were excluded. Etiology of heart failure was ischemic in 41%. RESULTS Anemia (hemoglobin<120 g/l) was present in 28 of 193 patients (15%). There was an inverse relationship between NYHA-class and left ventricular ejection fraction (NYHA-class I 45%, class II 32%, class III 25%, class IV 25%). Serum creatinine increased with NYHA-class. Hemoglobin levels were similar in all four NYHA-classes but there were significantly more patients with anemia in NYHA-class III and IV (19%) compared with class I and II (8%, P<0.05). Hemoglobin was similar in surviving patients (mean 140 g/l) and those who died or were transplanted (mean 136 g/l, ns). CONCLUSIONS The prevalence of anemia in our heart failure service is 15% (compared with 56% in the literature) and is correlated to NYHA-class.

Early and late outcome of operated and non-operated acute dissection of the descending aorta.

OBJECTIVE At present debate continues concerning the optimal mode of treatment for type B dissections. Controversies are mainly due to discordant results regarding survival following medical or surgical treatment. We assessed early and long-term outcome of acute dissection of the descending aorta treated by emergency aortic replacement, medical treatment or delayed surgery. METHODS Between 1980 and 1995, 225 patients were hospitalized in the medical or surgical department of our institution with the diagnosis of acute type B aortic dissection. A total of 38 patients (16.8%) underwent replacement of the descending aorta within the first week after hospital admission. Primary indications for immediate surgery were: rupturing aneurysm (n = 15), diameter of the descending aorta (n = 13), malperfusion of the thoracoabdominal aorta (n = 8) and pseudocoarctation syndrome with uncontrollable hypertension (n = 2). All other patients (n = 187) underwent primary conservative treatment on the intensive care unit, including appropriate anti-hypertensive medication. In 12 of them, surgery was denied because of age or significant concomitant diseases. RESULTS Hospital mortality after urgent or emergency surgery was 21% (8/38 patients) for the overall time period. There has been a significant decrease in hospital mortality during the last 5 year-period (12% versus 30% between 1980 and 1994). Causes of death were: cardiac failure in 3, bleeding complications in 2, postoperative mesenteric ischemia in 2 and septicemia in one patient. From the 30 operative survivors, 9 (30%) patients required further surgery on the native aorta after a mean follow-up of 48 +/- 13 months. Hospital mortality during conservative treatment was 17.6% (33/187 patients). Main causes of death were rupture in 14, thoraco-abdominal malperfusion in 13 and cardiac failure in 3 patients, whereas in 3 patients, the cause of death could not be evaluated. In this group, 9 patients had to be shifted to early surgery during the initial hospitalization because of impending rupture (n = 4), rapidly increasing diameter (n = 2) and suspicion of intestinal ischemia (n = 3). After hospital discharge, surgery for chronic dissection was performed in 47 patients, mainly because of expanding descending aortic aneurysm. Hospital mortality was 8% (4/47 patients). Actuarial survival rates after surgery during the first admission were 85 +/- 6% at 5 years and 61 +/- 8% at 10 years, versus 76 +/- 5 and 50 +/- 7% respectively, following conservative treatment (P < 0.001). CONCLUSION Nowadays, acute type B dissection can be treated surgically with a reasonable perioperative risk. Despite aggressive anti-hypertensive treatment, hospital mortality of primary conservative treatment is still high and a substantial percentage of patients requires surgery during initial hospitalization. Main causes of death in both groups are rupture and abdominal malperfusion: therefore, closed clinical and radiologic assessment of the whole thoraco-abdominal aorta is of utmost importance. Long-term results are satisfying; unlimited radiographic follow-up allows for detection of potential severe complications and for proper planning of elective reoperations when indicated.