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1. Renal and cardiac function during alpha1-beta-blockade in congestive heart failure.

Author

Heitmann M, Davidsen U, Stokholm KH, Rasmussen K, Burchardt H, and Petersen EB

Subjects
Aged, Aldosterone blood, Angiotensin II blood, Blood Pressure drug effects, Cardiac Output drug effects, Carvedilol, Diuretics therapeutic use, Drug Therapy, Combination, Glomerular Filtration Rate drug effects, Heart Failure physiopathology, Heart Rate drug effects, Humans, Middle Aged, Renal Circulation drug effects, Adrenergic beta-Antagonists therapeutic use, Angiotensin-Converting Enzyme Inhibitors therapeutic use, Carbazoles therapeutic use, Heart physiology, Heart Failure drug therapy, Kidney physiology, Propanolamines therapeutic use
Abstract

Unlabelled: The kidney and the neurohormonal systems are essential in the pathogenesis of congestive heart failure (CHF) and the physiologic response. Routine treatment of moderate to severe CHF consists of diuretics, angiotensin-converting enzyme (ACE) inhibition and beta-blockade. The need for control of renal function during initiation of ACE-inhibition in patients with CHF is well known. The aim of this study was to investigate whether supplementation by a combined alpha1-beta-blockade to diuretics and ACE-inhibition might improve cardiac function without reducing renal function., Methods: Fourteen patients treated for moderate to severe CHF with diuretics and ACE inhibitors were investigated at baseline, after 4 months of maximum carvedilol treatment and after withdrawal of carvedilol., Results: Carvedilol lowered blood pressure and heart rate but increased left and right ventricular ejection fractions without changing cardiac output or pulmonary blood volume. At the same time, a minor fall was seen in glomerular filtration rate (GFR). but renal blood flow was unchanged and effective renal plasma flow slightly increased. Carvedilol also lowered the plasma levels of angiotensin II and aldosterone. All changes were reversed after withdrawal of carvedilol., Conclusions: Carvedilol augments ACE-inhibitor-induced vasodilation by lowering blood pressure, and angiotensin II beside reducing heart rate. The heart adapts to the haemodynamic alterations without changes in cardiac output and pulmonary blood volume. GFR is slightly lowered despite no changes in renal blood flow and a slight increase in effective renal plasma flow. The study emphasizes the need for control of renal function during treatment with carvedilol in patients with CHF.

Published
2002
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2. Chronic congestive heart failure. Description and survival of 190 consecutive patients with a diagnosis of chronic congestive heart failure based on clinical signs and symptoms.

Author

Madsen BK, Hansen JF, Stokholm KH, Brøns J, Husum D, and Mortensen LS

Subjects
Adult, Aged, Exercise Test, Female, Heart Failure diagnosis, Heart Failure drug therapy, Heart Failure etiology, Heart Failure mortality, Humans, Male, Middle Aged, Multivariate Analysis, Prognosis, Prospective Studies, Stroke Volume, Survival Rate, Heart Failure physiopathology, Ventricular Function, Left
Abstract

The prognosis, and clinical findings related to prognosis, were examined in a consecutive series of 190 patients under 76 years of age (mean 64 years) with congestive heart failure (CHF). The aetiology of CHF was ischaemic heart disease in 66%, hypertension in 11% and cardiomyopathy in 23%. The 2-year mortality was 32%. Median left ventricular ejection fraction (LVEF) was 0.30, range 0.06 to 0.74. Eight per cent were in New York Heart Association (NYHA) class I, 46% in II, 44% in III and 2% in IV. Multivariate analysis, excluding exercise test variables, revealed seven variables with independent, significant prognostic information, (hazard ratios for death in brackets): ln (natural logarithm) (LVEF) (3.19), NYHA class III+IV (2.72), plasma urea > 7.6 mmol.l-1 (2.22), serum creatinine > 121 mumol.l-1 (2.05), serum sodium < or = 137 mmol.l-1 (2.03), pulmonary congestion on X-ray (1.86), and age > 65 years (1.86). Multivariate analysis, including exercise testing, showed the following variables to contain independent, significant prognostic information: increase in heart rate during maximal exercise < or = 35 min-1 (3.5), ln (LVEF) (3.7), serum creatinine > 121 mumol.l-1 (2.9), maximal exercise time < or = 4 min (2.3), serum sodium < or = 137 mmol.l-1 (2.5), ischaemic heart disease (2.0) and plasma urea > 7.6 mmol.l-1 (1.9). In conclusion, patients with CHF have a high risk of death despite intensive medical treatment. LVEF is a strong predictor of mortality. Both NYHA class and exercise variables have strong independent prognostic information as regards mortality in combination with LVEF, but are mutually exclusive.

Published
1994
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3. Plasma immunoreactive neuropeptide Y in congestive heart failure at rest and during exercise.

Author

Madsen BK, Husum D, Videbaek R, Stokholm KH, Saelsen L, and Christensen NJ

Subjects
Adult, Aged, Epinephrine blood, Female, Humans, Male, Middle Aged, Norepinephrine blood, Rest, Exercise physiology, Heart Failure blood, Neuropeptide Y blood
Abstract

The purpose of the study described here was to study plasma immunoreactive Neuropeptide Y (NPY) at rest and during exercise in patients with congestive heart failure (CHF) and in healthy subjects. Thirty-five patients, mean age 64 years, with CHF in optimal treatment and with a mean ejection fraction of 32%, were studied at rest and during exercise. Twelve age and sex matched healthy subjects were compared for resting values. Another nine healthy subjects were studied at rest and during exercise at a constant low load of 75W and at a high load defined as 80% of their individual maximal capacity. In patients with congestive heart failure mean plasma immunoreactive NPY at rest was 10.3 pmol l-1 and was not significantly different from the control group. No differences between patients with slight and severe CHF were found and there was no correlation between plasma immunoreactive NPY and left ventricular ejection fraction. Mean maximal exercise time was on average 6.3 min. Only three patients exercised more than 10 min. At maximal exercise mean plasma immunoreactive NPY was 10.6 pmol l-1 the same as at rest. Plasma noradrenaline was increased in CHF patients compared to healthy subjects, and rose further during exercise. In healthy subjects plasma immunoreactive NPY rose significantly on both workloads, but more on the high load (p < 0.05), when the rise was first significant after 10 min. Plasma immunoreactive NPY at rest and during exercise was not increased in CHF patients in optimal medical treatment. Consequently plasma immunoreactive NPY is not a useful marker of the severity of CHF in these patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1993

4. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Author

Granger, C, Massie, B, Somaratne, J, Ahmed, A, Cowie, M, Gonzalez-Juanatey, J, Gorini, M, Kearney, M, di Lenarda, A, Lenzen, M, Macin, S, Madsen, B, Maggioni, A, McAlister, F, Oliva, F, Rich, M, Richards, M, Squire, I, Taffet, G, Earle, N, Perera, K, Dobson, J, Pocock, S, Poppe, K, Whalley, G, Andersson, B, Hall, C, Richards, AM, Troughton, R, Lainchbury, J, Berry, C, Hogg, K, Norrie, J, Stevenson, K, Brett, M, McMurray, J, Pfeffer, MA, Granger, CB, Held, P, McMurray, JJV, Michelson, EL, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Lenzen, MJ, Reimer, WJMS, Boersma, E, Vantrimpont, PJMJ, Follath, F, Swedberg, K, Cleland, J, Komajda, M, Gotsman, I, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Grigorian-Shamagian, L, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, MA, Guazzi, M, Myers, J, Arena, R, McAlister, FA, Ezekowitz, J, Armstrong, PW, Cujec, B, Paterson, I, Cowie, MR, Wood, DA, Coats, AJS, Thompson, SG, Suresh, V, Poole-Wilson, PA, Sutton, GC, Martinez-Selles, M, Robles, JAG, Prieto, L, Munoa, MD, Frades, E, Diaz-Castro, O, Tarantini, L, Faggiano, P, Senni, M, Lucci, D, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Maggioni, AP, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, TM, Boesgaard, S, Hassager, C, Nielsen, OW, Aldershvile, J, Nielsen, H, Kober, L, Macin, SM, Perna, ER, Canella, JPC, Alvarenga, P, Pantich, R, Rios, N, Farias, EF, Badaracco, JR, Madsen, BK, Hansen, JF, Stokholm, KH, Brons, J, Husum, D, Mortensen, LS, Bayes-Genis, A, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Almendral, J, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, AB, Newton, JD, Blackledge, HM, Squire, IB, Wright, SP, Whalley, GA, Doughty, RN, Kerzner, R, Gage, BF, Huynh, BC, Rovner, A, Freedland, KE, Carney, RM, Rich, MW, Taffet, GE, Teasdale, TA, Bleyer, AJ, Kutka, NJ, Luchi, RJ, Tribouilloy, C, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsutsui, H, Tsuchihashi, M, Takeshita, A, MacCarthy, PA, Kearney, MT, Cubbon, R, Nolan, J, Lee, AJ, Prescott, RJ, Shah, AM, Brooksby, WP, Fox, KAA, Varela-Roman, A, Gonzalez-Juanatey, JR, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, JL, and Gude, F

Subjects
Meta-analysis, Heart failure, Prognosis
Abstract

A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF epsilon 50. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28), and have a history of hypertension (51 vs. 41). Ischaemic aetiology was less common (43 vs. 59) in patients with HF-PEF. There were 121 [95 confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95 CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95 CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40. Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Published
2012

5. The survival of patients with heart failure with preserved or reduced left ventricular ejection fraction: an individual patient data meta-analysis

Author

Berry C, Doughty RN, Granger C, Kober L, Massie B, McAlister F, McMurray J, Pocock S, Poppe K, Swedberg K, Somaratne J, Whalley GA, Ahmed A, Andersson B, Bayes-Genis A, Cowie M, Cubbon R, Ezekowitz J, Gonzalez-Juanatey J, Gorini M, Gotsman I, Grigorian-Shamagian L, Guazzi M, Kearney M, Komajda M, di Lenarda A, Lenzen M, Lucci D, Macin S, Madsen B, Maggioni A, Martinez-Selles M, Oliva F, Rich M, Richards M, Senni M, Squire I, Taffet G, Tarantini L, Tribouilloy C, Troughton R, Tsutsui H, Earle N, Perera K, Dobson J, Whalley G, Hall C, Richards AM, Lainchbury J, Hogg K, Norrie J, Stevenson K, Brett M, Pfeffer MA, Granger CB, Held P, McMurray JJV, Michelson EL, Olofsson B, Ostergren J, Yusuf S, Torp-Pedersen C, Lenzen MJ, Reimer WJMS, Boersma E, Vantrimpont PJMJ, Follath F, Cleland J, Zwas D, Planer D, Azaz-Livshits T, Admon D, Lotan C, Keren A, Varela-Roman A, Mazon-Ramos P, Rigeiro-Veloso P, Bandin-Dieguez MA, Gonzalez-Juanatey JR, Myers J, Arena R, McAlister FA, Armstrong PW, Cujec B, Paterson I, Cowie MR, Wood DA, Coats AJS, Thompson SG, Suresh V, Poole-Wilson PA, Sutton GC, Robles JAG, Prieto L, Munoa MD, Frades E, Diaz-Castro O, Almendral J, Faggiano P, Bertoli D, Porcu M, Opasich C, Tavazzi L, Maggioni AP, Kirk V, Bay M, Parner J, Krogsgaard K, Herzog TM, Boesgaard S, Hassager C, Nielsen OW, Aldershvile J, Nielsen H, Macin SM, Perna ER, Canella JPC, Alvarenga P, Pantich R, Rios N, Farias EF, Badaracco JR, Madsen BK, Hansen JF, Stokholm KH, Brons J, Husum D, Mortensen LS, Vazquez R, Puig T, Fernandez-Palomeque C, Bardaji A, Pascual-Figal D, Ordonez-Llanos J, Valdes M, Gabarrus A, Pavon R, Pastor L, Fiol M, Nieto V, Macaya C, Cinca J, de Luna AB, Newton JD, Blackledge HM, Squire IB, Wright SP, Kerzner R, Gage BF, Freedland KE, Rich MW, Huynh BC, Rovner A, Carney RM, Taffet GE, Teasdale TA, Bleyer AJ, Kutka NJ, Luchi RJ, Rusinaru D, Mahjoub H, Souliere V, Levy F, Peltier M, Tsuchihashi M, Takeshita A, MacCarthy PA, Kearney MT, Nolan J, Lee AJ, Prescott RJ, Shah AM, Brooksby WP, Fox KAA, Basante P, Trillo R, Garcia-Seara J, Martinez-Sande JL, Gude F, Berry, C, Doughty, R, Granger, C, Kober, L, Massie, B, Mcalister, F, Mcmurray, J, Pocock, S, Poppe, K, Swedberg, K, Somaratne, J, Whalley, G, Ahmed, A, Andersson, B, Bayes-Genis, A, Cowie, M, Cubbon, R, Ezekowitz, J, Gonzalez-Juanatey, J, Gorini, M, Gotsman, I, Grigorian-Shamagian, L, Guazzi, M, Kearney, M, Komajda, M, di Lenarda, A, Lenzen, M, Lucci, D, Macin, S, Madsen, B, Maggioni, A, Martinez-Selles, M, Oliva, F, Rich, M, Richards, M, Senni, M, Squire, I, Taffet, G, Tarantini, L, Tribouilloy, C, Troughton, R, Tsutsui, H, Earle, N, Perera, K, Dobson, J, Hall, C, Richards, A, Lainchbury, J, Hogg, K, Norrie, J, Stevenson, K, Brett, M, Pfeffer, M, Held, P, Michelson, E, Olofsson, B, Ostergren, J, Yusuf, S, Torp-Pedersen, C, Reimer, W, Boersma, E, Vantrimpont, P, Follath, F, Cleland, J, Zwas, D, Planer, D, Azaz-Livshits, T, Admon, D, Lotan, C, Keren, A, Varela-Roman, A, Mazon-Ramos, P, Rigeiro-Veloso, P, Bandin-Dieguez, M, Myers, J, Arena, R, Armstrong, P, Cujec, B, Paterson, I, Wood, D, Coats, A, Thompson, S, Suresh, V, Poole-Wilson, P, Sutton, G, Robles, J, Prieto, L, Munoa, M, Frades, E, Diaz-Castro, O, Almendral, J, Faggiano, P, Bertoli, D, Porcu, M, Opasich, C, Tavazzi, L, Kirk, V, Bay, M, Parner, J, Krogsgaard, K, Herzog, T, Boesgaard, S, Hassager, C, Nielsen, O, Aldershvile, J, Nielsen, H, Perna, E, Canella, J, Alvarenga, P, Pantich, R, Rios, N, Farias, E, Badaracco, J, Hansen, J, Stokholm, K, Brons, J, Husum, D, Mortensen, L, Vazquez, R, Puig, T, Fernandez-Palomeque, C, Bardaji, A, Pascual-Figal, D, Ordonez-Llanos, J, Valdes, M, Gabarrus, A, Pavon, R, Pastor, L, Fiol, M, Nieto, V, Macaya, C, Cinca, J, de Luna, A, Newton, J, Blackledge, H, Wright, S, Kerzner, R, Gage, B, Freedland, K, Huynh, B, Rovner, A, Carney, R, Teasdale, T, Bleyer, A, Kutka, N, Luchi, R, Rusinaru, D, Mahjoub, H, Souliere, V, Levy, F, Peltier, M, Tsuchihashi, M, Takeshita, A, Maccarthy, P, Nolan, J, Lee, A, Prescott, R, Shah, A, Brooksby, W, Fox, K, Basante, P, Trillo, R, Garcia-Seara, J, Martinez-Sande, J, and Gude, F

Subjects
Male, medicine.medical_specialty, Prognosi, Heart failure, Lower risk, Risk Factors, Cause of Death, Internal medicine, medicine, Humans, Meta-analysi, Aged, Randomized Controlled Trials as Topic, Ejection fraction, business.industry, Hazard ratio, Stroke Volume, Atrial fibrillation, medicine.disease, Confidence interval, Meta-analysis, Cardiology, Etiology, Female, Cardiology and Cardiovascular Medicine, business
Abstract

Aims A substantial proportion of patients with heart failure have preserved left ventricular ejection fraction (HF-PEF). Previous studies have reported mixed results whether survival is similar to those patients with heart failure and reduced EF (HF-REF). Methods and results We compared survival in patients with HF-PEF with that in patients with HF-REF in a meta-analysis using individual patient data. Preserved EF was defined as an EF ≥ 50%. The 31 studies included 41 972 patients: 10 347 with HF-PEF and 31 625 with HF-REF. Compared with patients with HF-REF, those with HF-PEF were older (mean age 71 vs. 66 years), were more often women (50 vs. 28%), and have a history of hypertension (51 vs. 41%). Ischaemic aetiology was less common (43 vs. 59%) in patients with HF-PEF. There were 121 [95% confidence interval (CI): 117, 126] deaths per 1000 patient-years in those with HF-PEF and 141 (95% CI: 138, 144) deaths per 1000 patient-years in those with HF-REF. Patients with HF-PEF had lower mortality than those with HF-REF (adjusted for age, gender, aetiology, and history of hypertension, diabetes, and atrial fibrillation); hazard ratio 0.68 (95% CI: 0.64, 0.71). The risk of death did not increase notably until EF fell below 40%. Conclusion Patients with HF-PEF have a lower risk of death than patients with HF-REF, and this difference is seen regardless of age, gender, and aetiology of HF. However, absolute mortality is still high in patients with HF-PEF highlighting the need for a treatment to improve prognosis.

Published
2012

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