Andrew J. Galbraith

Diastolic ventricular interaction in chronic heart failure

BACKGROUND Diastolic ventricular interaction describes a situation in which the volume of one ventricle is directly influenced by the volume of the other ventricle. Such interaction is normally negligible, but it is accentuated in circumstances associated with pulmonary hypertension and volume overload. When this interaction occurs, acute volume unloading results in a reduction in right ventricular end-diastolic volume, as expected, but left ventricular end-diastolic volume paradoxically increases. Since chronic heart failure is a volume-overloaded state associated with pulmonary hypertension, we hypothesised that this interaction may be clinically important in patients with heart failure. METHODS A radionuclide technique incorporating cardiac scintigraphy was used to measure the effect of acute volume unloading, achieved by 30 mm Hg lower-body suction, on right and left ventricular end-diastolic volumes in 21 patients with chronic heart failure and 12 healthy individuals (controls). FINDINGS In nine heart-failure patients, there was a paradoxical increase in left ventricular end-diastolic volume in association with an expected decrease in right ventricular end-diastolic volume during lower-body suction. This response was not seen in the control group. The mean change in left ventricular end-diastolic volume differed significantly between the heart-failure patients and controls (6 [SD 19] vs -19 [12] mL, p = 0.0003). However, the change in right ventricular end-diastolic volume was similar in the two groups (-18 [11] vs -20 [8]%. p = 0.70). Patients who increased left ventricular end-diastolic volume during lower-body suction had higher resting pulmonary arterial and pulmonary capillary wedge pressures than the remaining heart-failure patients. INTERPRETATION The response of nine patients in our study suggests diastolic ventricular interaction, which we believe could be common in patients with chronic heart failure. This finding is relevant to their management, since it emphasises the importance of venodilator therapy. The relation between stroke volume and left ventricular end-diastolic volume, by the Frank-Starting law of the heart, may explain why some patients with chronic heart failure paradoxically increase stroke volume when pulmonary capillary wedge pressure is lowered with vasodilators.

Lack of effect of coenzyme Q on left ventricular function in patients with congestive heart failure.

OBJECTIVES This study evaluated the effects of oral therapy with coenzyme Q on echocardiographic and hemodynamic indexes of left ventricular function and on quality of life in patients with chronic left ventricular dysfunction. BACKGROUND Coenzyme Q a coenzyme for oxidative phosphorylation and an antioxidant and free radical scavenger. It has been claimed to improve symptoms, quality of life, left ventricular ejection fraction and prognosis in patients with cardiac failure. METHODS Thirty patients with ischemic or idiopathic dilated cardiomyopathy and chronic left ventricular dysfunction (ejection fraction 26 +/- 6%) were randomized to a double-blind crossover trial of oral coenzyme Q versus placebo each for 3 months. Right heart pressures, cardiac output and echocardiographic left ventricular volumes were measured at baseline and after each treatment phase, and quality of life was assessed using the Minnesota Living With Heart Failure questionnaire. It was calculated that to demonstrate an increase in left ventricular ejection fraction from 25% to 30% with a standard deviation of 5% using 95% confidence intervals with a power of 80% we would require 17 patients. RESULTS Twenty-seven completed both treatment phases. There was no significant difference in left ventricular ejection fraction, cardiac volumes or hemodynamic and quality of life indices after treatment with coenzyme Q placebo, although plasma coenzyme Q levels increased from 903 +/- 345 nmol/l(-1) to 2,029 +/- 856 nmol/l(-1). CONCLUSIONS Inpatients with left ventricular dysfunction, treatment for three months with oral coenzyme Q failed to improve resting left ventricular systolic function or quality of life despite an increase in plasma levels of coenzyme Q to more than twice basal values

Arg389Gly-[beta]1-adrenergic receptors determine improvement in left ventricular systolic function in nonischemic cardiomyopathy patients with heart failure after chronic treatment with carvedilol

Objective Administration of the &bgr;-adrenergic receptor blocker carvedilol to patients with chronic heart failure leads to clinically significant benefits, including improvement in left ventricular systolic function in some, but not all, patients. We sought to determine the basis of the variable effect obtained with carvedilol in patients with heart failure. Carvedilol blocks both &bgr;1-adrenergic and &bgr;2-adrenergic receptors, and both receptors exist as polymorphisms. We aimed to determine whether these polymorphisms contribute to variability in response to carvedilol in patients with chronic heart failure. Methods We retrospectively and prospectively investigated 135 patients with nonischemic cardiomyopathy and chronic stable heart failure (New York Heart Association class II, III) treated with carvedilol. Baseline echocardiography was obtained before introduction of carvedilol and repeated after stabilization of a maximally tolerated dose of carvedilol (50–100 mg/day) for at least 1 year. Polymerase chain reaction and restriction fragment length polymorphism analysis were used to genotype &bgr;1-adrenergic and &bgr;2-adrenergic receptor polymorphisms. Results When grouped according to receptor polymorphisms patients were well matched for severity of heart failure, comorbidity and treatment. No significant difference was observed in baseline left ventricular ejection fraction (LVEF) between groups (P>0.05). After 1.5 years of treatment with carvedilol patients with Arg389Arg-&bgr;1-adrenergic receptors had a significantly greater improvement in LVEF compared with Gly389 carriers (Arg389Arg 18.8%; Arg389Gly 9.4%; Gly389Gly 6.0%; P<0.001) whereas there were no differences attributable to other &bgr;1-adrenergic and &bgr;2-adrenergic receptor polymorphisms (P>0.05). Conclusion In patients with nonischemic dilated cardiomyopathy, carvedilol leads to a significantly greater improvement in LVEF in patients with the Arg389Arg-&bgr;1 adrenergic receptor phenotype.

Acitretin for prophylaxis of cutaneous malignancies after cardiac transplantation

BACKGROUND Heart transplant recipients have an increased risk of developing actinic keratoses and non-melanotic skin cancers when compared with the general population. Systemic retinoids have been shown to be beneficial in the treatment of such lesions in recipients of other organs, but as of yet the heart transplant model has rarely been studied. In this investigation we describe our experience with the use of acitretin in a group of heart transplant patients. METHODS Five heart transplant recipients with multiple new skin cancer presentations were treated with acitretin at doses of either 10 or 25 mg/day. Inclusion criteria were based on progressive actinic keratoses, recurrent skin malignancies or continuous lesions despite treatment with appropriate topical therapies. Patients were excluded if they were women of child-bearing age, had severe hepatic or renal impairment or were taking contraindicated medications. RESULTS Over the treatment period all patients showed a reduction in the number of new non-melanotic skin cancers excised and histologically confirmed. Three patients had a very large reduction and 2 patients had a more moderate reduction in the number of new presentations. All patients had an objective decrease in the number of actinic keratoses. All patients tolerated the drug well with only 1 patient transiently discontinuing the Acitretin due to side effects. No significant alterations in the biochemical tests or serum lipids were reported. CONCLUSIONS Over the treatment period, low-dose acitretin proved a valuable addition in the long-term strategy of reduction and treatment of non-melanotic skin cancers in heart transplant recipients with multiple skin cancers and actinic keratoses.

Echocardiographic Description of Recurrent Idiopathic Giant-Cell Myocarditis in Cardiac Allograft

A 23-year-old woman with a cardiac allograft transplanted for giant-cell myocarditis 4 years earlier presented with exertional dyspnea. Her chest x-ray showed a normal cardiothoracic ratio and mild pulmonary venous congestion. An ECG demonstrated sinus rhythm with partial right bundle branch block. Conventional echocardiogram was essentially normal with only the interventricular septum being severely hypokinetic. The left ventricle (LV) was of normal size with low-normal systolic function (Figure 1). The right ventricle was of normal size and function. There was mild tricuspid regurgitation with a right ventricular systolic pressure of 31 mm Hg. There was no significant pericardial effusion. Doppler mitral inflow and pulmonary venous flow indices showed abnormal LV relaxation and …

Cardiac transplantation for prosthetic valve endocarditis in a previously transplanted heart

Native valve endocarditis is a rare complication after heart transplantation.1,2,3 A 54-year-old male underwent cardiac transplantation for end-stage ischemic cardiomyopathy in March 1992. The immediate postoperative course was complicated by primary graft failure requiring high-dose inotropic support and the intra-aortic balloon pump. Acute renal failure developed and continuous arteriovenous hemodialysis was undertaken for 8 days. The patient received triple immunosuppression with cyclosporine, azathioprine, and prednisone, without induction therapy. The patient became febrile and severe mitral regurgitation and mitral valve vegetations were noted 36 days after the transplant by echocardiography. Blood cultures grew methicillin-resistant Staphylococcus aureus (MRSA). A CT scan of his head revealed 2 lesions consistent with septic emboli. He remained febrile despite treatment with vancomycin and fuscidic acid with adequate blood levels. An aminoglycoside was not used because MRSA in this institution is resistant. Because of uncontrolled sepsis with blood cultures persistently growing MRSA, the patient underwent mitral valve replacement with a St. Jude prosthesis 42 days after the transplant. At operation massive vegetations were found on the mitral valve leaflets and the infection was eroding the annulus. Postoperatively, he developed acute renal failure and required 3 further days of continuous arteriovenous hemodialysis. The same antibiotics were continued postoperatively. Seventeen days later, severe mitral regurgitation developed due to a paravalvar leak. The patient remained febrile and 1 blood culture was positive for MRSA. Transesophageal echocardiography demonstrated a paravalvar leak with adjacent vegetations. Because of ongoing sepsis and severe heart failure, retransplantation was undertaken 103 days after his original transplant. He received triple immunosuppression with 3 doses of OKT3. Cyclosporine levels were run at one-half the usual level, azathioprine at 50 mg per day, and prednisolone at 10 mg per day. The explanted heart showed dehiscence of 50% of the sewing ring of the mitral valve prosthesis and MRSA was cultured from the annulus. Eleven days after his retransplant procedure Candida albicans was grown from a pleural drain. Four months after his second transplant he developed signs and echocardiographic features of constrictive pericarditis. An attempt was made to perform a pericardiectomy but this proved technically impossible. Pericardial fluid contained white blood cells and C. albicans was grown. He underwent a course of amphotericin followed by fluconazole. Eight months following his retransplantation he developed lower back pain and nuclear magnetic resonance imaging revealed a discitis of the fourth lumbar disk, a 7-cm abdominal aortic aneurysm, and an abscess in continuity with these 2 lesions. He underwent resection of this mycotic abdominal aortic aneurysm and subsequently, removal of the infected disk material (MRSA was grown) which did not involve the epidural space. He received vancomycin postoperatively. He has evidence of moderately severe chronic constrictive pericarditis and has had intermittent low-grade fevers for which no cause has been found despite extensive evaluation. No organisms have been cultured from his blood, blood count and erythrocyte sedimentation rate are normal, and repeated transthoracic and transesophageal echocarFrom the Heart and Lung Transplant Unit, The Prince Charles Hospital, Brisbane, Australia,a and the University of Alabama at Birmingham, Department of Surgery, Birmingham, Alabama.b Submitted June 19, 1996; accepted February 12, 1999. Corresponding author: David C. McGiffin, MB, BS, FRACS, Professor of Surgery, University of Alabama at Birmingham, Division of Cardiothoracic Surgery, UAB Station, LHRB 780, Birmingham, Alabama 35294-0007. Office telephone: 205-9346580. Fax: 205-975-2526. Copyright

Non-toxigenic corynebacterium diphtheriae var gravis endocarditis of the aortic valve

Abstract A patient developed non-toxigenic Corynebacterium diphtheriae var gravis aortic valve endocarditis with a large left ventricular wall abscess. end infection was managed by debridement of the abscess and replacement of the aortic valve by an aortic homograft valve. Persisting infection allowed the abscess cavity to erode into the ventricular wall. The infection was controlled by closure of the abscess cavity following instillation of a mixture of antibiotic and biological glue. Reoperation was subsequently required to close residual communications between the cavity and aorta and left ventricle. The patient was well 4 years after the last procedure.