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Gene transfer into the donor heart during cold preservation for heart transplantation.

BACKGROUND: Ex vivo gene transfer to heart grafts may hold promise as a means of changing alloreactivity or xenoreactivity after transplantation. However, it remains to be determined how effectively gene transfer can be accomplished within a short time in cold-stored grafts that are ready to be transplanted. METHODS: We performed an experimental study using a replication-defective adenovirus (Adex1CALacZ) encoding the Escherichia coli beta-galactosidase (beta-gal) gene to perform gene transfer to heart grafts awaiting transplantation. Thirty hearts of Wistar rats were removed and their coronary arteries were perfused with University of Wisconsin solution containing 1 x 10(9), 1 x 10(10), or 1 x 10(11) plaque-forming units of the recombinant adenovirus at 4 degrees C for 60 minutes. As a control, other hearts were perfused with University of Wisconsin solution with an adenoviral vector that did not contain the beta-gal gene (Adex1w1) for the same period. After perfusion, the grafts were implanted in the necks of syngeneic adult rats. The grafts were removed each week after transplantation and their expression of beta-gal was assessed by 5-bromo-4-chloro-3-indoyl-beta-D-galactoside staining. RESULTS: Successful gene transfer and expression of the beta-gal gene were demonstrated in adenovirus-perfused hearts. Gene transfer occurred preferentially in the cardiomyocytes over the endothelial cells and smooth muscle cells of the coronary vessels. In hearts perfused with 1 x 10(9) plaque-forming units of the adenovirus, gene expression persisted for 4 weeks after transfer, but it diminished gradually and was minimal by day 28. Histologic analyses revealed slight inflammatory reactions in the myocardium. In hearts perfused with 1 x 10(10) and 1 x 10(11) plaque-forming units of the adenovirus, beta-gal diminished 3 weeks after transplantation and a prominent infiltration of leukocytes was recognized in the myocardium. CONCLUSIONS: This study demonstrated that the cardiomyocytes of heart grafts express an exogenous gene product after adenovirus-mediated gene transfer under hypothermic preservation conditions. However, immune or inflammatory reactions to recombinant adenoviruses must be taken into account when a large number of adenoviruses are injected into the coronary arteries.

Adenoviridae↗

Prevalence of left-ventricular systolic dysfunction and heart failure in the Echocardiographic Heart of England Screening study: a population based study.

BACKGROUND: Accurate data for prevalence rates for heart failure due to various causes, and for left-ventricular systolic dysfunction in all adults are unavailable. Our aim was to assess prevalence of left-ventricular systolic dysfunction and heart failure in a large representative adult population in England. METHODS: Of 6286 randomly selected patients aged 45 years and older, 3960 (63%) participated in the study. They came from 16 randomly selected general practices. We assessed patients by history and examination, electrocardiography, and echocardiography. Prevalence of left-ventricular systolic dysfunction (defined as ejection fraction <40%) and heart failure was calculated for the overall population on the basis of strict criteria and, when necessary, adjudication by a panel. FINDINGS: Left-ventricular systolic dysfunction was diagnosed in 72 (1.8% [95% CI 1.4-2.3]) participants, half of whom had no symptoms. Borderline left-ventricular function (ejection fraction 40-50%) was seen in 139 patients (3.5% [3.0-4.1]). Definite heart failure was seen in 92 (2.3%, [1.9-2.8]) and was associated with an ejection fraction of less than 40% in 38 (41%) patients, atrial fibrillation in 30 (33%), and valve disease in 24 (26%). Probable heart failure was seen in a further 32 (0.8% [0.6-1.1]) patients. In total, 124 (3.1% [2.6-3.7]) patients aged 45 years or older had definite or probable heart failure. INTERPRETATION: Heart failure is often misdiagnosed or underdiagnosed in primary care. Our results suggest that assessment of left-ventricular function in patients with suspected heart failure could lead to more effective diagnosis and treatment of this disorder.

Aged↗

Do results of the ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study spell the end for non-selective endothelin antagonism in heart failure?

The last two decades have seen major advances in the treatment of chronic heart failure, primarily as a result of therapeutic manipulation of activated neurohormonal systems. Despite this progress, many patients still suffer significant morbidity and premature death. Antagonism of the biological effects of endothelin, a potent vasoconstrictor, represents a further potential target. To date, positive results from animal models of heart failure have not been translated into clinical practice, perhaps as a consequence of the high doses of drug used. The ENABLE (Endothelin Antagonist Bosentan for Lowering Cardiac Events in Heart Failure) study evaluated the effects of low dose bosentan, a non-selective endothelin receptor antagonist, in patients with severe heart failure (left ventricular ejection fraction <35%, New York Heart Association class IIIb-IV). A total of 1,613 patients were randomized to receive either bosentan (125 mg twice a day) or placebo. The preliminary results were presented at the 51st Annual Scientific Session of the American College of Cardiology (17-20 March 2002, Atlanta, GA, USA). The primary endpoint of all-cause mortality or hospitalization for heart failure was reached in 321/808 patients on placebo and 312/805 receiving bosentan. Treatment with bosentan appeared to confer an early risk of worsening heart failure necessitating hospitalization, as a consequence of fluid retention. It has been suggested that further studies using even lower doses of bosentan or more aggressive concomitant diuretic therapy may avoid this adverse effect. The results from the ENABLE study have, however, thrown further doubt on the potential benefits of non-specific endothelin receptor blockade in heart failure.

Antihypertensive Agents↗

Congenital heart disease: the original heart failure syndrome.

Heart failure is characterised by a triad comprising cardiac abnormality, exercise limitation and neurohormonal activation. The 2% of the adult population who suffer with heart failure are known to derive both symptomatic and prognostic benefit from exercise and pharmacologic neurohormonal antagonism. The existence of heart failure has traditionally been considered in the context of ischaemic, hypertensive, valvular and myopathic disease but in this article we develop the argument that patients with congenital heart disease also manifest all the pathophysiological criteria that constitute the chronic heart failure syndrome. We discuss the inherent limitations to a purely anatomical approach to congenital heart disease, bring attention to the large and rapidly growing population of adults with this condition and conclude by calling for a therapeutic approach to congenital heart disease that is based on the heart failure paradigm.

Adult↗

Nurse-led heart failure clinics improve survival and self-care behaviour in patients with heart failure: results from a prospective, randomised trial.

AIM: The aim of this trial was to prospectively evaluate the effect of follow-up at a nurse-led heart failure clinic on mortality, morbidity and self-care behaviour for patients hospitalised due to heart failure for 12 months after discharge. METHODS: A total of 106 patients were randomly assigned to either follow-up at a nurse-led heart failure clinic or to usual care. The nurse-led heart failure clinic was staffed by specially educated and experienced cardiac nurses, delegated the responsibility for making protocol-led changes in medications. The first follow-up visit was 2-3 weeks after discharge. During the visit the nurse evaluated the heart failure status and the treatment, gave education about heart failure and social support to the patient and his family. RESULTS: There were fewer patients with events (death or admission) after 12 months in the intervention group compared to the control group (29 vs 40, p=0.03) and fewer deaths after 12 months (7 vs 20, p=0.005). The intervention group had fewer admissions (33 vs 56, p=0.047) and days in hospital (350 vs 592, p=0.045) during the first 3 months. After 12 months the intervention was associated with a 55% decrease in admissions/patient/month (0.18 vs 0.40, p=0.06) and fewer days in hospital/patient/month (1.4 vs 3.9, p=0.02). The intervention group had significantly higher self-care scores at 3 and 12 months compared to the control group (p=0.02 and p=0.01). CONCLUSIONS: Follow up after hospitalisation at a nurse-led heart failure clinic can improve survival and self-care behaviour in patients with heart failure as well as reduce the number of events, readmissions and days in hospital.

Aged↗

Clinical profile and management of heart failure: rural community hospital vs. metropolitan heart center.

BACKGROUND: Knowledge on clinical characteristics and prognosis of patients with heart failure originates from studies of selected populations in clinical trials or from epidemiological observations. Reports on the large numbers of patients with heart failure treated in community hospitals are sparse. OBJECTIVE: Are there differences in patient characteristics and heart failure management between a metropolitan heart center (HC) and a rural community hospital (RCH)? PATIENTS AND METHODS: Retrospective analysis of medical charts from all patients admitted for heart failure (ICD 428.x, NYHA II-IV, EF<45%) between May 1997 and April 1998 and discharged alive from a rural community hospital. A similar, but prospective registry was available at the HC. Follow-up information was obtained by request at registration authorities. RESULTS: Patient groups comprised 120 in RCH and 146 in HC. Mean age was 75+/-11 and 66+/-11 years, respectively (P<0.001); 48% (RCH) vs. 74% (HC) of patients were male (P<0.001). On admission the proportion of functional class IV was 69% (RCH) vs. 17% (HC) (P<0.001). At discharge, the rate of ACE-inhibitors was 74% (RCH) vs. 98% (HC); 11% (RCH) vs. 43% (HC) of patients received beta-blocker therapy. Ninety-six percent of patients in HC underwent and 22% in RCH had undergone invasive diagnostics. One-year mortality rate of patients discharged alive was 26% in RCH and 19% in HC (P=n.s. after adjustment for age and gender). CONCLUSION: Heart failure management according to current guidelines, using beta-blockers and ACE inhibitors, and invasive cardiac examination was significantly less performed in the rural community hospital than in the metropolitan heart center. Therefore, strategies to improve heart failure management according to guidelines are urgently needed.

Adrenergic beta-Antagonists↗

Dissociating beliefs about heart rates and actual heart rates in patients with cardiac pacemakers.

Performance on heartbeat counting tasks is usually interpreted in terms of cardiac sensitivity. We tested the hypothesis that heartbeat counting is influenced by beliefs about heart rates by dissociating beliefs about heart rates and actual heart rates. In a within-subjects design, heart rates of 50 patients with cardiac pacemakers were set to a low (50 bpm), medium (75 bpm), or high (110 bpm) pacing rate unknown to the patients via remote control while they performed a heartbeat tracking task. Results showed that patients' heartbeat counting did not follow the shifts in their actual heart rates adequately, although their overall performance was comparable to that of young and healthy control participants. As a result, tracking scores decreased significantly in the high pacing rate condition where beliefs about heart rates and actual heart rates were most extremely dissociated. The findings suggest that tracking scores reflect beliefs about heart rates rather than cardiac sensitivity.

Adult↗

The role of inflammatory mediators in the failing heart: immunomodulation of cytokines in experimental models of heart failure.

Congestive heart failure may be produced by a variety of disorders, including dilated cardiomyopathy, hypertension, and ischemic heart disease. We have developed experimental models of these diseases, and found gene expressions of proinflammatory cytokines increased in the hearts of these animals. Various drugs for heart failure modulate the production of cytokines in experimental models of heart failure. Pimobendan, an inhibitor of phosphodiesterase III prolonged survival, attenuated inflammatory lesions, and decreased the production of cytokines and nitric oxide. Recent studies have shown that these inhibitory effects are due to inhibition of activation of NF-kappaB. In contrast, digitalis increased the production of cytokines and exacerbated myocarditis. Interleukin-10 prolonged survival, attenuated myocardial injury, and appears promising as a treatment of heart failure due to viral myocarditis. Endothelin-1 plays an important pathophysiological role in heart failure, and treatment with an endothelin antagonist had a cardioprotective effect in experimental models of heart failure.

Adjuvants, Immunologic↗

Co-culture of embryonic chick heart cells and ciliary ganglia induces parasympathetic responsiveness in embryonic chick heart cells.

We have developed a system for the co-culture of embryonic chick heart cells obtained from embryos at 3.5 days in ovo with ciliary ganglia from chick embryos at 7 days in vivo. After 3 days of co-culture, removal of the ciliary ganglia resulted in complete degeneration of axons within 6-8 h, leaving the post-innervated heart cell culture devoid of neurons. Embryonic chick heart cells at 3.5 days in ovo are unresponsive to muscarinic stimulation. However, following 3 days of co-culture with ciliary ganglia, the heart cells developed a negative chronotropic response to muscarinic stimulation (paired t test, P < 0.02) which persisted for at least 24 h after removal of the ciliary ganglion. The development of muscarinic responsiveness was associated with an increase in the levels of specific alpha-subunits of the guanine nucleotide binding proteins (G-proteins), with a 3-fold increase in the level of alpha 39 (39 kDa subunit) and a 2.5-fold increase in the level of alpha 41. The level of the G-protein subunit alpha s remained unchanged. Culture of embryonic chick heart cells at 3.5 days in ovo with medium conditioned by the growth of embryonic chick heart cells and ciliary ganglia had an effect on the chronotropic response to muscarinic stimulation and on alpha 39 and alpha 41 levels identical to that of co-culture. These data suggest that a soluble factor released during the co-culture of embryonic chick heart cells and ciliary ganglia is capable of inducing muscarinic responsiveness. These studies suggest that innervation of the heart may induce parasympathetic responsiveness by increasing the availability of G-proteins which couple the muscarinic receptor to a physiological response.

Animals↗

A placebo-controlled study examining the effect of allopurinol on heart rate variability and dysrhythmia counts in chronic heart failure.

AIMS: Allopurinol improves endothelial function in chronic heart failure by reducing oxidative stress. We wished to explore if such an effect would attenuate autonomic dysfunction in CHF in line with many other effective therapies in CHF. METHODS: We performed a prospective, randomized, double-blind cross-over study in 16 patients with NYHA Class II-IV chronic heart failure (mean age 67 +/- 10 years, 13 male, comparing allopurinol (2 months) at a daily dose of 300 mg (if creatinine < 150 micromol l-1) or 100 mg (if creatinine > 150 micromol l-1) with matched placebo. Mean heart rate and dysrhythmia counts were recorded from 24 h Holter tapes at monthly intervals for 6 months. We assessed autonomic function using standard time domain heart rate variability parameters (HRV): SDNN, SDANN, SDNN index, rMSSD and TI. RESULTS: Allopurinol had no significant effect on heart rate variability compared with placebo; the results are expressed as a difference in means +/- s.d. with 95% confidence interval (CI) between allopurinol and placebo: SDNN mean = 6.5 +/- 4.8 ms, P = 0.18 and 95% CI (-3.7, 17); TI mean = -2.1 +/- 1.4, P = 0.16 and 95% CI (-5.2, 0.8); SDANN mean = -2.8 +/- 7 ms, P = 0.68 and 95% CI (-18, 12); SDNNi mean = 2 +/- 6.6, P = 0.7 and 95% CI (-12, 16); RMSSD mean = -0.9 +/- 2, P = 0.68 and 95% CI (-5.6, 3.7). For mean heart rate the corresponding results were 0.9 +/- 1.4, P = 0.5 and 95% CI (-2, 3.8). Log 24 h ventricular ectopic counts (VEC) were 0.032 +/- 0.37, P = 0.7 and 95% CI (-0.1, 0.2). Patient compliance with study medication was good since allopurinol showed its expected effect of reducing plasma uric acid (P < 0.001). CONCLUSIONS: Allopurinol at doses, which are known to reduce oxidative stress appear to have no significant effect on resting autonomic tone, as indicated by time domain heart rate variability or on dysrhythmia count in stable heart failure patients.

Aged↗

[Analysis of Foetal Heart Rate Data using Complex Software: Comparison of Recurrence Plot of Foetal Heart Rate with the Course of Pregnancy -].

BACKGROUND: Is it useful to further analyse foetal heart rate to improve the prediction of pregnancy complications? The analysis of the foetal heart rate is usually based on the variability of the heart rate, i. e. the more variable the heart rate presents - except a decrease - the better the condition of the foetus is. The same concept is applied in our own analysis which differs only in the presentation of the data. MATERIAL AND METHODS: We analysed 25 non-stress-tests from unselected third trimester pregnancies using sophisticated software. The recurrence plot (RP) is able to rearrange data from foetal heart rate monitoring in order to make the heart rate variability visible. We developed criteria for a normal and an abnormal test result describing the structure of the diagram to predict an uneventful and a high-risk pregnancy, respectively. RESULTS: 11 out of 11 patients with uneventful course and outcome of pregnancy showed a coarse and blurred RP pattern. 12 out of 14 (86 %) patients developing either intrauterine growth retardation or preeclampsia and requiring caesarean section because of foetal heart rate abnormalities showed a fine and clear RP pattern. CONCLUSIONS: Our preliminary results show that it makes sense to further evaluate foetal heart rate variability in order to predict pregnancy complications. Computer programs including the algorithms needed (calculation of the recurrence plot) are not expensive and easy to handle. A widespread use of these programs represents the basis requirement for large controlled clinical trials.

Analysis of Variance↗

Heart diseases affecting the liver and liver diseases affecting the heart.

BACKGROUND: The association of cardiac and liver disorders has not been extensively outlined in the literature. METHODS: A survey of the MEDLINE database was performed to assess the current status of research regarding the association between cardiac and liver disorders. RESULTS: Combined cardiac and hepatic disorders occur in 3 different settings: heart diseases affecting the liver, liver diseases affecting the heart, and cardiac and hepatic disorders with joint etiology. The spectrum of heart diseases affecting the liver includes mild alterations of liver function tests in heart failure, cardiogenic ischemic hepatitis, congestive liver fibrosis, and cardiac cirrhosis. The liver diseases affecting the heart include complications of cirrhosis such as hepatopulmonary syndrome, portopulmonary hypertension, pericardial effusion, and cirrhotic cardiomyopathy as well as noncirrhotic cardiac disorders such as high-output failure caused by intrahepatic arteriovenous fistulae. Cardiac and hepatic disorders with joint etiology include infectious, metabolic, immune, vasculitic, and toxic disorders. We propose a practical approach to a diagnostic workup of combined cardiac and hepatic disorders based on recognizing the sequence of appearance of the cardiac and liver disease, presence of features of a multisystem disease, and presence of pathognomonic features. The evaluation of combined cardiac and hepatic disorders takes into consideration the expected benefit of treatment and the risks related to invasive procedures. Accordingly, investigations can be limited to ancillary tests for patients with congested liver and mild alterations of liver function tests, in cardiogenic ischemic hepatitis, patients with cardiac cirrhosis who are proposed for conservative treatment, and multisystem disease involving the heart and the liver. Conversely, comprehensive investigations are recommended when invasive therapeutic interventions are considered for the treatment of hepatopulmonary syndrome, portopulmonary hypertension, or arteriovenous fistulae. CONCLUSION: Classification of a patient to any of the 3 categories-heart diseases affecting the liver, liver diseases affecting the heart, and cardiac and hepatic disorders with joint etiology-permits the physician to narrow the span of the possible diagnoses and allows for a more simple workup.

Comorbidity↗

Improved right heart function after myocardial preservation with 2,3-butanedione 2-monoxime in a porcine model of allogenic heart transplantation.

BACKGROUND: Right heart dysfunction is a major cause for early morbidity and mortality after heart transplantation. Experiments were designed to evaluate the influence of the calcium-desensitizing drug 2,3-butanedione 2-monoxime (BDM) on right heart function in a porcine model of heart transplantation. METHODS: Donor hearts of domestic pigs were arrested with BDM in Krebs solution (n = 7) and with BDM in Bretschneider's histidine-tryptophan-ketoglutarate (HTK) solution (n = 6). There were 2 control groups: University of Wisconsin (UW, n = 6) and HTK (n = 6). An isovolumic model was used in which the right ventricular volume was precisely controlled in vivo with an intracavitary high-compliance balloon. After 4 hours of ischemia, hearts were transplanted into recipients. After 1 and 2 hours of reperfusion, the right ventricular balloon volume was increased in 10-mL increments until right ventricular failure occurred and the developed pressures were recorded. RESULTS: Maximal right ventricular developed pressures were significantly different after 2 hours of reperfusion (UW: 35 +/- 13 mm Hg; HTK: 47 +/- 8 mm Hg; Krebs+BDM: 49 +/- 9 mm Hg; HTK+BDM: 50 +/- 6 mm Hg; P =.04). Hearts subjected to BDM could be loaded with a significantly increased volume after 1 hour and after 2 hours (UW: 57 +/- 10 mL vs HTK: 43 +/- 8 mL vs Krebs+BDM: 70 +/- 10 mL vs HTK+BDM: 67 +/- 15 mL; P =.002). Postischemic right ventricular enddiastolic compliance was significantly increased in groups treated with BDM after 1 hour (P =.02) and after 2 hours (P =.039). CONCLUSIONS: The drug BDM significantly improves right ventricular function in a heart transplantation model. The increase in volume load and developed right ventricular pressure achieved by BDM application would translate into a decreased risk of right ventricular failure after clinical transplantation.

Adenosine↗

Simultaneous measurement of instantaneous heart rate and chest wall plethysmography in short-term, metronome guided heart rate variability studies: suitability for assessment of autonomic dysfunction.

Instantaneous heart rate and chest wall motion were measured using a 3-lead ECG and an air pressure chest wall plethysmography system. Chest wall plethysmography traces were found to accurately represent the breathing pattern as measured by spirometry (average correlation coefficient 0.944); though no attempt was made to calibrate plethysmography voltage output to tidal volume. Simultaneous measurements of heart rate and chest wall motion were made for short periods under metronome guided breathing at 6 breaths per minute. The average peak to trough heart rate change per breath cycle (AVEMAX) and maximum correlation between heart rate and breathing cycle (HRBRCORR) were measured. Studies of 44 normal volunteers indicated clear inverse correlation of heart rate variability parameters with age (AVEMAX R = -0.502, P < 0.001) but no significant change in HRBRCORR with age (R = -0.115). Comparison of normal volunteers with diabetics with no history of symptoms associated with autonomic failure indicated significant lower heart rate variability in diabetics (P = 0.005 for AVEMAX) and significantly worse correlation between heart rate and breathing (P < 0.001 for HRBRCORR). Simultaneous measurement of heart rate and breathing offers the possibility of more sensitive diagnosis of autonomic failure in a simple bedside test and gives further insight into the nature of cardio-ventilatory coupling.

Adult↗

Outcome in patients with end-stage renal disease following heart or heart--lung transplantation receiving peritoneal dialysis.

BACKGROUND: End-stage renal disease (ESRD) complicates 5--10% of heart and heart--lung transplant patients. We report our experience of peritoneal dialysis (PD) in 17 such patients. METHODS: Between March 1995 and February 1999, 13 heart transplant and four heart--lung transplant patients (11 male, 6 female) joined our PD programme (10 continuous ambulatory PD, seven automated PD). Median time from heart or heart--lung transplantation to ESRD was 9 years (range 1--13 years), and median age at introduction of renal replacement therapy was 51 years (range 23--66 years). The frequency of exit-site infections, peritonitis, and PD survival (including technique failure and death) in the transplant group (TxP) was calculated retrospectively. These were compared with two contemporary control groups: PD patients immunosuppressed for other indications (ISP, n=19) and, all other patients recruited onto the PD programme (NISP, n=132). RESULTS: Median follow-up was 10 months (range 2--27 months) for TxP, 7 months (range 2--29 months) for ISP, and 14 months (range 1--48 months) for NISP groups. The frequency of exit-site infections was similar in each group: 1 in 26 months for TxP; 1 in 30 months for ISP, and 1 in 27 months for NISP (P=NS). The frequency of peritonitis was greater in the TxP group at 1 in 15 months, compared with 1 in 20 months for ISP and 1 in 29 months for NISP (TxP vs NISP, P<0.05). PD failure following infection was 23.5% for TxP, 10.5% for ISP, and 12.9% for NISP. Actuarial PD survival at 24 months was only 25.2% in the TxP group compared with 79% in the NISP group. There were no deaths related to immediate complications of PD. CONCLUSIONS: Increased risk of PD peritonitis and reduced PD survival is reported in this cohort of 17 heart and heart--lung recipients with ESRD. Nevertheless, for patients with severely impaired cardiac function, PD may still offer therapeutic advantage.

Adolescent↗

Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies.

The associations between heart rate and death from the cardiovascular diseases (CVD), coronary heart disease (CHD) and sudden death from CHD, along with death from all causes and non-cardiovascular causes, are examined for three groups of middle-aged white males: 1233 men aged 40-59 years followed for 15 years from the Chicago Peoples Gas Company study; 1899 men aged 40-55 years followed for 17 years from the Chicago Western Electric Company study; and 5784 men aged 45-64 years followed an average of five years from the Chicago Heart Association Detection Project in Industry. In univariate analyses, mortality from both cardiovascular and non-cardiovascular causes generally increases with increasing heart rate. In bivariate analyses, using the Cox regression model to control for age, heart rate is significantly related to mortality from all causes in each study, with the associations again due to both cardiovascular and non-cardiovascular causes. In multivariate Cox regression, controlling for age, blood pressure, serum cholesterol, cigarettes smoked per day and relative weight, heart rate is a significant risk factor for sudden CHD death and non-CVD death in two of the three studies, with the association with sudden death being U-shaped in one of the studies. Although heart rate may be an independent risk factor for sudden CHD death, the associations with other CVD death and non-sudden CHD death, in general, appear to be secondary to associations between heart rate and other cardiovascular risk factors.

Adult↗

Reshaping our perception of the typical hospitalized heart failure patient: a gender analysis of data from the ADHERE Heart Failure Registry.

Heart failure studies have suggested important differences between women and men both in heart failure etiology and in survival. Clinical trials and long-standing perceptions of the typical heart failure patient have related far more to men than to women, while more women than men in the United States may be hospitalized with heart failure. The goal of this study was to analyze ADHERE Registry data, the largest database of acute decompensated heart failure (ADHF) patient hospitalizations available, to gain insight into the effect of gender on medical history, clinical characteristics, and discharge counseling. This preliminary study analyzed the 85,617 ADHF hospitalizations in the ADHERE Registry as of October 2003, with 44,340 (52%) women and 41,276 (48%) men included. Women were significantly older (mean age 74.6 +/- 13.7 years) than men (mean age 70.2 +/- 13.9 years, P < .0001). Women were more likely to have a history of hypertension (75% vs. 69%, P < .0001) and a systolic blood pressure > 140 mm Hg (56% vs. 44%, P < .0001). History of coronary artery disease was more common in men (64% vs. 51%, P < .0001). Other risk factors for atherosclerosis, including smoking (17% vs. 10%, P < .0001) and hyperlipidemia (37% vs. 32%, P < .0001), were also more common in men. Men had a significantly lower mean left ventricular ejection fraction (32.9%, N = 30,831) than women (42.1%, N = 29,744); 51% of women had preserved left ventricular function (EF > 40%) compared to only 28% of men (P < 0.0001). At discharge, adherence to 3 of the 4 JCAHO standardized measures of quality of care far heart failure patients were documented more frequently for men than for women. A significantly smaller proportion of women received discharge instructions on management of diet, weight, and medications (30.1% vs. 32.8%); received or were scheduled for assessment of left ventricular function (81.5% vs. 85.6%); or were discharged with an angiotensin converting enzyme inhibitor prescription if appropriate (72.6% vs. 73.9%). Real-world data from the ADHERE Registry may lead to better recognition of the signs and symptoms of heart failure in women, increase the proportion of women who are correctly diagnosed, and may help to support gender-specific considerations in heart failure guidelines.

Aged↗

Long term results of heart transplantation in patients with amyloid heart disease.

OBJECTIVE: To determine the outcome of heart transplantation for end stage amyloid heart disease in patients treated at a single centre. DESIGN: Records of all patients with amyloid heart disease who underwent heart transplantation were examined to determine survival, graft involvement by amyloid, the course of systemic amyloid disease, and the cause of death. PATIENTS: 10 patients, mean (SD) age 54 (8) years, received transplants in the 13 year period 1984 to 1997. RESULTS: Two patients, both with AL amyloid (primary systemic amyloidosis), died perioperatively. Mean follow up in the remaining eight patients was 49.9 (39.5) months (range 3-116 months). Amyloid deposits in the grafts became evident histologically in five patients with AL amyloid at 5, 11, 12, 28, and 30 months after transplantation, and in one patient with familial amyloid at 60 months. Echocardiography showed no evidence of left ventricular systolic impairment at the time of recurrence. Seven patients died, at 3, 11, 26, 32, 49, 85, and 116 months after transplantation; four of these deaths were related to amyloidosis. Actuarial survival at one and two years was 60% and at five years, 30%. CONCLUSIONS: Heart transplantation for amyloid heart disease remains controversial because of the scarcity of hearts for transplantation, the systemic nature of amyloidosis, and the potential for amyloid deposition in the graft. Postoperative mortality was high (20%), reflecting extracardiac amyloid. Heart transplantation for end stage cardiac amyloidosis is feasible but, without treatment of the underlying process, it is a palliative procedure.

Adult↗