Peter Bergin

Adverse consequences of high sympathetic nervous activity in the failing human heart

OBJECTIVES In view of previous experimental evidence relating sympathetic nervous overactivity in the heart to myocardial necrosis and ventricular arrhythmias, we prospectively examined the hypothesis that heightened cardiac sympathetic nervous activity is associated with an adverse outcome in patients with moderate to severe heart failure. BACKGROUND Despite recent therapeutic advances, patients with heart failure continue to have high mortality from progressive hemodynamic decompensation and lethal ventricular arrhythmias. It is believed that initially compensatory increases in sympathetic nervous system activity may ultimately be maladaptive, potentially contributing to subsequent adverse events. METHODS Sixty patients with moderate to severe heart failure (left ventricular ejection fraction 18.9 +/- 0.9% [mean +/- SE]) were studied prospectively. In addition to the compilation of a hemodynamic, biochemical and electrocardiographic profile for each patient, whole-body and cardiac sympathetic activity were determined by isotope dilution. The relation of these variables to outcome was determined by Cox proportional hazards analysis. RESULTS The mean follow-up period of the study group was 7 +/- 1 months (range 1 to 24) with a 12-month actuarial survival of 75%. Deaths (14 in all) were accounted for either by sudden death or progressive heart failure in equal numbers. The rate of release of norepinephrine from the heart was significantly higher in patients with heart failure than in healthy subjects (402 +/- 37 vs. 105 +/- 19 pmol/min, p < 0.01), although the values for heart failure ranged widely from normal to 10 times normal. By univariate Cox proportional hazards analysis, pulmonary capillary wedge pressure (p < 0.01), mean pulmonary artery pressure (p < 0.001), serum sodium levels (p < 0.01) and cardiac norepinephrine spill-over rate (p < 0.001) were identified as significant prognostic markers. In a multivariate analysis, cardiac norepinephrine spillover rate was identified as the most powerful prognostic marker (p = 0.0006) of those evaluated in this study. CONCLUSIONS These results suggest that activation of the sympathetic nervous system in patients with heart failure, specifically the cardiac sympathetic nerves, may contribute to the poor prognosis associated with severe heart failure. The data therefore provide a rationale for the use of drugs such as beta-adrenergic blocking agents in the management of patients with heart failure.

Influence of Pulmonary Capillary Wedge Pressure on Central Apnea in Heart Failure

BACKGROUND Recent studies suggest that acute pulmonary congestion induces hyperventilation and that hyperventilation-related hypocapnia leads to ventilatory control instability and central sleep apnea. Whether chronic pulmonary congestion due to congestive heart failure (CHF) is associated with central apnea is unknown. We hypothesized that CHF patients with central apnea would have greater pulmonary capillary wedge pressure (PCWP) than patients without central apnea and that PCWP would correlate with central apnea severity. METHODS AND RESULTS Seventy-five stable CHF patients underwent right heart catheterization and, on the basis of overnight sleep studies, were divided into central apnea (n=33), obstructive apnea (n=20), or nonapnea groups (apnea-hypopnea index [AHI] <5 events per hour). Mean PCWP was significantly greater in the central than in the obstructive and nonapnea groups (mean+/-SEM [range]: 22. 8+/-1.2 [11 to 38] versus 12.3+/-1.2 [4 to 21] versus 11.5+/-1.5 [3 to 28] mm Hg, respectively; P<0.001). Within the central apnea group, PCWP correlated with the frequency and severity of central apnea (AHI: r=0.47, P=0.006) and degree of hypocapnia (PaCO2: r=-0.42, P=0. 017). Intensive medical therapy in 7 patients with initially high PCWP and central apneas reduced both PCWP (29.0+/-2.6 [20 to 38] to 22.0+/-1.8 [17 to 27] mm Hg; P<0.001) and central apnea frequency (AHI) (38.5+/-7.7 [7 to 62] to 18.5+/-5.3 [1 to 31] events per hour; P=0.005). CONCLUSIONS PCWP is elevated in CHF patients with central apneas compared with those with obstructive apnea or without apnea. Moreover, a highly significant relationship exists between PCWP, hypocapnia, and central apnea frequency and severity.

Increased long-term mortality in heart failure due to sleep apnoea is not yet proven

Previous small-scale studies of the effect of sleep-disordered breathing (SDB) on prognosis in congestive heart failure (CHF) are either lacking or conflicting. The aim of this study was to assess the impact of the presence and type of SDB on mortality in a patient group with severe CHF referred to a specialised heart failure centre. Out of 78 patients ((mean±sd) 53±9 yrs, left ventricular ejection fraction 19.9±7.2% and pulmonary capillary wedge pressure 16.5±8.3 mmHg) followed-up over a median period of 52 months, 29% had no apnoea (CHF‐N), 28% had obstructive sleep apnoea (CHF‐OSA) and 42% had central sleep apnoea (CHF‐CSA). At 52 months, their overall mortality was 40%, and combined mortality and transplantation was 72%. Mortality rates were similar between the three apnoea groups. Survivors had a similar prevalence of SDB (71%) as the nonsurvivors (70%). Although a significant increase in mortality was evident at 500 days in those patients with either CHF‐SDB or CHF‐CSA as compared with CHF‐N, this was not significant at final follow-up (52 months) using Kaplan Meier analysis. Multivariate analysis identified transplantation but not SDB type or severity as a significant predictor of survival. In conclusion, sleep-disordered breathing impacts upon early (500 day), but not long-term (52 month), mortality in a specialised heart failure centre.

Extracorporeal Membrane Oxygenation in Primary Graft Failure After Heart Transplantation

BACKGROUND The aim of this review was to analyze our results with extracorporeal membrane oxygenation (ECMO) support for primary graft failure (PGF) in heart transplant recipients. METHODS A retrospective review of 239 consecutive patients who underwent heart transplantation between January 2000 and August 2009 was performed. Orthotopic, heterotopic, and heart lung transplants were included in this analysis. Over that time period, 54 patients developed PGF, of whom 39 patients required ECMO support. These 39 patients form the basis of this review. RESULTS Thirty-four patients (87%) were successfully weaned from ECMO and 29 (74.3%) survived to hospital discharge. There were no significant differences in wean rates or complications between central and peripheral ECMO. Comparison of survival in the 39 ECMO patients to the non-PGF patients (n = 185) showed a significantly worse survival in the ECMO group (p = 0.007). When those patients who died in the first 30 days were excluded, there was no difference in overall survival between groups (p = 0.73). CONCLUSIONS Extracorporeal membrane oxygenation provides excellent circulatory support for patients with PGF after heart transplantation with good wean and survival to discharge rates.

Dietary supplementation with l-arginine fails to restore endothelial function in forearm resistance arteries of patients with severe heart failure

OBJECTIVES We sought to examine the efficacy of dietary supplementation of L-arginine on endothelium-dependent vasodilation in patients with congestive heart failure. BACKGROUND Endothelial dysfunction, as evidenced by a diminished response to such vasodilators as acetylcholine, is well defined in patients with heart failure. These responses are improved by intraarterial infusion with L-arginine. Because L-arginine is a semi-essential amino acid, we investigated the effects of dietary L-arginine on endothelium-dependent vasodilation in these patients. METHODS Twenty patients with heart failure (New York Heart Association functional class III/IV, mean [+/- SE] age 51.3 +/- 1.7 years) and seven healthy control subjects (mean age 52.6 +/- 3.3 years) were studied. All patients continued taking their usual treatment. Responses to acetylcholine and sodium nitroprusside were determined using forearm plethysmography. Patients with heart failure received either L-arginine (20 g/day every day for 28 days) or placebo (vehicle syrup in equal amounts) in a double-blind protocol. The calculated power of the study was between 62% and 80% to detect a 30% to 40% change in area under the dose-response (forearm vascular resistance) curve. RESULTS Responses to acetylcholine, but not to sodium nitroprusside, were significantly attenuated in patients with heart failure compared with control subjects (mean area under curve [AUC], control subjects vs. patients with heart failure: 1,125.4 +/- 164.5 vs. 617.3 +/- 116.6 U, p < 0.05, by Student t test). A significant increase in urea and aspartate transaminase levels in patients receiving active L-arginine treatment was observed. Responses to acetylcholine (AUC; before vs. after L-arginine: 641.5 +/- 126.7 vs. 695.9 +/- 151.9 U) and sodium nitroprusside were not affected by either L-arginine or placebo. CONCLUSIONS Endothelial dysfunction was apparent in patients with heart failure despite rigorous vasoactive treatment. Oral administration with L-arginine was ineffective in influencing endothelial function in these patients.

Improved outcomes from a comprehensive management system for heart failure.

Congestive heart failure (CHF) is associated with a high readmission rate after diagnosis. We assessed the ability of a comprehensive management program (CMP) for CHF to reduce readmissions with secondary endpoints of improving quality of life, exercise capacity and targeted drug doses.

Diagnostic performance of multisequential cardiac magnetic resonance imaging in acute cardiac allograft rejection

We evaluated cardiac magnetic resonance imaging (CMR) as a non‐invasive test for cardiac allograft rejection.

Bridge to recovery with a left ventricular assist device for fulminant acute myocarditis

Acute fulminant myocarditis frequently causes circulatory collapse that is resistant to conventional therapy. We describe a case in which a patient with histologically confirmed viral myocarditis was supported by a left ventricular assist device (LVAD) as a bridge to recovery. The LVAD was successfully weaned 3 weeks later.

Prolonged cardiac allograft ischemic time – no impact on long‐term survival but at what cost?

Abstract:  Introduction:  The aim of this paper was to review the outcomes of cardiac transplantation with regards to short‐ and long‐term survival, focusing particularly on patients who receive organs with long ischemic times and the resource utilization necessary to support such patients through their postoperative period.

Post–cardiac transplantation gout: incidence of therapeutic complications

OBJECTIVE To study the clinical impact of gout treatment following cardiac transplantation. METHODS We performed an audit of all cardiac transplant recipients of the Alfred Hospital before August 1998 who lived in Victoria. RESULTS We studied 225 patients (81% men), with a mean post-transplant follow-up of 50.8 months (SD 36). Forty-three (19%) had pre-transplant gout, 19 recurring post-transplantation. Twenty-three patients developed gout de novo. Of the 24 patients who received allopurinol, 6 developed pancytopenia and required hospitalization. Fourteen received a change in immunosuppression: in 5 patients following pancytopenia, and in 9 to enable safe use of allopurinol. Thirty-two patients received colchicine; 5 developed neuromyopathy. Impaired renal function, diuretic use, and hypertension were more common in this sub-group. Non-steroidal anti-inflammatory agents, used in 16 patients, caused serious complications in 1 patient (life-threatening peptic ulceration and hemorrhage, precipitating dialysis-dependent chronic renal failure). CONCLUSIONS Cardiac transplant recipients, when treated for gout, are at high risk of therapeutic complications. Thus, gout treatment significantly affects care, health, and immunosuppression of these patients.