Safety of adenosine pharmacologic stress myocardial perfusion imaging in orthotopic cardiac transplant recipients: a single center experience of 102 transplant patients.

Denervation super-sensitivity to adenosine is well described in cardiac transplant (CT) patients particularly early after transplant. The safety and hemodynamic effects of adenosine SPECT (A-SPECT) has not been described in a large series of CT patients. Single center retrospective study of 102 CT patients undergoing A-SPECT were compared to an age-gender matched patients in a 2:1 fashion who underwent A-SPECT in the same time period. Multivariate logistic regression model were used to identify independent predictors of advanced AV block. The average time from CT to A-SPECT was 8.5 ± 4.5 years. Average age was 57 years with 80% males. In comparison to the control group, adenosine infusion was associated with a higher incidence of sinus pause (4.9% vs. 0%), 2nd (11.8% vs. 4.9%) and 3rd degree AVB (2.9% vs. 0%) in CT patients (all P < 0.05). Prior use of aspirin and baseline 1st degree AVB were significant independent predictors of adenosine induced AVB. Baseline right or left bundle branch block, beta-blockers, calcium blockers or digoxin were not associated with occurrence of AVB. Only 1.9% of A-SPECT studies were terminated due to bradyarrythmia with 1 patient requiring aminophylline. There were no significant immediate or long term adverse events in these patients. Adenosine pharmacologic stress is associated with a higher incidence of AVB and sinus pause in CT patients reflecting persistence of super sensitivity late after CT. Nevertheless these bradyarrythmias are transient without any sequelae suggesting that A-SPECT can be performed safely in CT patients.

Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure.

INTRODUCTION: Inotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established. METHODS: Ten patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25-0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-alpha, soluble Fas, and soluble Fas-ligand were performed at both time points. RESULTS: Troponin was elevated at baseline in all patients (mean 0.1259 +/- 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 +/- 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-alpha, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline. CONCLUSION: In conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.

Effects of continuous aortic flow augmentation in patients with exacerbation of heart failure inadequately responsive to medical therapy: results of the Multicenter Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy (MOMENTUM).

BACKGROUND: Prior investigations suggest that superimposing continuous flow on aortic flow (continuous aortic flow augmentation) produces vasodilation, cardiac unloading, and improved cardiac performance. METHODS AND RESULTS: We compared percutaneous continuous aortic flow augmentation (flow

Rationale, design, and methods for a pivotal randomized clinical trial of continuous aortic flow augmentation in patients with exacerbation of heart failure: the MOMENTUM trial.

BACKGROUND: For patients hospitalized with heart failure (HF) who are inadequately responsive to medical therapy, the options include ventricular assist devices and cardiac transplant. In animal models and patients, continuous aortic flow augmentation using the Orqis Medical Cancion System (Orqis Medical Corporation, Lake Forest, California), a percutaneously placed arterial-to-arterial circuit (continuous flow up to 1.5 L/min) with an extracorporeal, magnetic, centrifugal pump, improves hemodynamics and renal function with benefits persisting 24 hours after discontinuation. METHODS AND RESULTS: The Multi-center Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy is enrolling patients hospitalized with HF who are randomized to continuous aortic flow augmentation or medical therapy alone. Entry requires persistent HF, elevated pulmonary capillary wedge pressure, reduced cardiac index, and impaired renal function or substantial diuretic requirement despite intravenous inotrope or vasodilator treatment. The primary efficacy end point is a composite including the components of 72- to 96-hour pulmonary capillary wedge pressure reduction and days alive out of hospital with no mechanical support for more than 35 days. Additional end points include changes in serum creatinine, N-terminal pro-B-type natriuretic peptide, and health-related quality of life. CONCLUSIONS: The Multi-center Trial of the Orqis Medical Cancion System for the Enhanced Treatment of Heart Failure Unresponsive to Medical Therapy tests the hypothesis that continuous aortic flow augmentation improves the clinical status and outcomes in patients hospitalized with HF exacerbation who are inadequately responsive to medical therapy.

Continuous aortic flow augmentation: a pilot study of hemodynamic and renal responses to a novel percutaneous intervention in decompensated heart failure.

BACKGROUND: Diminished aortic flow may induce adverse downstream vascular and renal signals. Investigations in a heart failure animal model have shown that continuous aortic flow augmentation (CAFA) achieves hemodynamic improvement and ventricular unloading, which suggests a novel therapeutic approach to patients with heart failure exacerbation that is inadequately responsive to medical therapy. METHODS AND RESULTS: We studied 24 patients (12 in Europe and 12 in the United States) with heart failure exacerbation and persistent hemodynamic derangement despite intravenous diuretic and inotropic and/or vasodilator treatment. CAFA (mean+/-SD 1.34+/-0.12 L/min) was achieved through percutaneous (n=19) or surgical (n=5) insertion of the Cancion system, which consists of inflow and outflow cannulas and a magnetically levitated and driven centrifugal pump. Hemodynamic improvement was observed within 1 hour. Systemic vascular resistance decreased from 1413+/-453 to 1136+/-381 dyne.s.cm(-5) at 72 hours (P=0.0008). Pulmonary capillary wedge pressure decreased from 28.5+/-4.9 to 19.8+/-7.0 mm Hg (P<0.0001), and cardiac index (excluding augmented aortic flow) increased from 1.97+/-0.44 to 2.27+/-0.43 L.min(-1).m(-2) (P=0.0013). Serum creatinine trended downward during treatment (overall P=0.095). There were 8 complications during treatment, 7 of which were self-limited. Hemodynamics remained improved 24 hours after CAFA discontinuation. CONCLUSIONS: In patients with heart failure and persistent hemodynamic derangement despite intravenous inotropic and/or vasodilator therapy, CAFA improved hemodynamics, with a reduction in serum creatinine. CAFA represents a promising, novel mode of treatment for patients who are inadequately responsive to medical therapy. The clinical impact of the observed hemodynamic improvement is currently being explored in a prospective, randomized, controlled trial.

Mechanism of atrial flutter occurring late after orthotopic heart transplantation with atrio-atrial anastomosis.

OBJECTIVE: We sought to better define the electrophysiologic mechanism of atrial flutter in patients after heart transplantation. BACKGROUND: Atrial flutter is a recognized problem in the post-cardiac transplant population. The electrophysiologic basis of atrial flutter in this patient population is not completely understood. METHODS: Six patients with cardiac allografts and symptoms related to recurrent atrial flutter underwent diagnostic electrophysiologic study with electroanatomic mapping and radiofrequency catheter ablation. Comparison was made with a control non-transplant population of 11 patients with typical counterclockwise right atrial flutter. RESULTS: In each case, mapping showed typical counterclockwise activation of the donor-derived portion of the right atrium, with concealed entrainment shown upon pacing in the cavotricuspid isthmus (CTI). The anastomotic suture line of the atrio-atrial anastomosis formed the posterior barrier of the reentrant circuit. Ablation of the electrically active, donor-derived portion of the CTI was sufficient to terminate atrial flutter and render it noninducible. Comparison with the control population showed that the electrically active portion of the CTI was significantly shorter in patients with transplant-associated flutter and that ablation was accomplished with the same or fewer radiofrequency lesions. CONCLUSIONS: Atrial flutter in cardiac transplant recipients is a form of typical counterclockwise, isthmus-dependent flutter in which the atrio-atrial anastomotic suture line forms the posterior barrier of the reentrant circuit. Ablation in the donor-derived portion of the CTI is sufficient to create bidirectional conduction block and eliminate this arrhythmia. Ablation or surgical division of the donor CTI at the time of transplantation could prevent this arrhythmia.

Nesiritide for secondary pulmonary hypertension in patients with end-stage heart failure.

PURPOSE: The impact of adding nesiritide to standard therapy and positive inotropic agents in patients with end-stage heart failure and secondary pulmonary hypertension (PH) was studied. METHODS: Patients included in this retrospective study were 18 years of age or older, admitted to the hospital with PH secondary to end-stage heart failure (New York Heart Association functional class IV), had received a pulmonary artery catheter, had been treated with nesiritide because of inadequate hemodynamic response to previous therapy (pulmonary capillary wedge pressure [PCWP], >18 mm Hg), and had shown minimal symptomatic benefit from standard heart-failure therapy, continuous infusions of loop diuretics, and positive inotropic agents (milrinone or dobutamine or both). The primary endpoint was change in PCWP. Secondary endpoints included change in mean pulmonary artery pressure (MPAP), change in cardiac index (CI), change in mean arterial pressure (MAP), change in serum creatinine (SCr) concentration, and occurrence of symptomatic hypotension. RESULTS: The study included 33 patients. Mean PCWP was reduced by 31.1% with the addition of nesiritide to previous therapy (p < 0.0001). Significant improvements in other hemodynamic variables, including MPAP (15.6% reduction) and CI (13.0% increase), were also observed. MAP was reduced significantly (by 15.2%), but SCr concentration did not change. There were five episodes of symptomatic hypotension. All patients exhibited relief of dyspnea symptoms. CONCLUSION: The addition of nesiritide to standard therapy and positive inotropic agents improved hemodynamic measures and clinical symptoms in patients with end-stage heart failure and secondary pulmonary hypertension.

Congestive heart failure.

Preview Patients with congestive heart failure generally have a poor prognosis, and sudden death is common. Concepts of management have changed drastically through the years, in hopes that predisposing factors can be modified. In this article, Drs Hobbs and Czerska give an overview of the problem and examine the status of pharmacologic therapy and various surgical techniques.