Insights into ventricular repolarization abnormalities in cardiac allograft vasculopathy.

We investigated the relationship of QT dispersion and cardiac allograft vasculopathy in heart transplant recipients. The findings suggest that the development of cardiac allograft vasculopathy is associated with an increase in QT dispersion, suggesting the presence of abnormal repolarization in these patients.

Reduction in QT dispersion with rheolytic thrombectomy in acute myocardial infarction: evidence of electrial stability with reperfusion therapy.

An increase in QT dispersion (QTd) is associated with myocardial ischemia and may serve as a marker of ischemia and ventricular arrhythmia. We studied the effect of early reperfusion with rheolytic thrombectomy using an angiojet catheter (Possis, Minneapolis, MN) on QTd in 12 patients who presented with acute myocardial infarction. QTd and QT dispersion, rate-corrected for RR interval, were significantly reduced from 57 +/- 16 and 68 +/- 13 msec before reperfusion to 34 +/- 16 and 44 +/- 19 msec after reperfusion respectively (mean +/- SD; P < 0.002 and P < 0.0008, respectively). Successful reperfusion with rheolytic thrombectomy reduces QTd and may confer electrical stability to vulnerable myocardium. Reduction in indexes of repolarization inhomogeneity with reperfusion may serve as a noninvasive marker of coronary patency.

Effects of aerobic exercise training on indices of ventricular repolarization in patients with chronic heart failure.

BACKGROUND: Patients with chronic heart failure (CHF) have a markedly increased incidence of malignant ventricular arrhythmias. QT dispersion (QTd), defined as the difference between maximal and minimal QT intervals, reflects the regional inhomogeneity of ventricular repolarization dispersion and may mark the presence of malignant ventricular arrhythmias. PURPOSE: To determine the effects of exercise training on QTd in patients with CHF. PATIENTS: Fifteen patients with CHF and ejection fractions < 40% (mean, 28+/-9%) who were on a stable medical regimen. DESIGN AND INTERVENTION: Standardized 12-lead surface ECGs were obtained at the beginning and end of the exercise training program, and QT and JT intervals were measured manually and corrected for heart rate by using Bazett's formula. QTd, heart rate-corrected QTd (QTc-d), JT dispersion (JTd), and heart rate-corrected JTd (JTc-d) were measured in at least eight ECG leads in each patient. RESULTS: Following the cardiac rehabilitation and exercise training programs, patients with CHF had only slight improvements in exercise capacity (results were not significant). However, these patients had marked improvements in QTd (71+/-11 to 59+/-17 ms; p < 0.02), QTc-d (82+/-28 to 63+/-17 ms; p < 0.01), JTd (76+/-19 to 57+/-18 ms; p < 0.002), and JTc-d (84+/-23 to 61+/-18 ms; p < 0.001) following the exercise training programs. CONCLUSION: These data indicate that aerobic exercise training significantly reduces the indices of ventricular repolarization dispersion in patients with CHF. Further studies are needed to evaluate how effectively this reduction in ventricular repolarization dispersion decreases the risk of malignant ventricular arrhythmias and sudden death in patients with CHF.

Intravenous thyroid hormone supplementation in heart failure with cardiogenic shock.

BACKGROUND: Thyroid hormone level abnormalities commonly exist in severe heart failure and may be of prognostic value. The therapeutic potential of using thyroid hormone for cardiogenic shock resulting from progressive heart failure has not been previously delineated. We sought to evaluate the role of an intravenous infusion of thyroxine as an adjunct to conventional inotropic agents and intra-aortic balloon counterpulsation in patients with severe heart failure with cardiogenic shock. METHODS AND RESULTS: We studied 10 consecutive patients with severe systolic heart failure that progressed to a cardiogenic shock state unresponsive to conventional pharmacological inotropic measures. Intravenous thyroxine (20 micrograms/h) was used as an adjunctive salvage measure after the failure of conventional pharmacological and mechanical support by intra-aortic balloon pump. The invasive hemodynamic profile (right atrial pressure, pulmonary capillary wedge pressure, cardiac index, mean arterial pressure), overall clinical status, core temperature, renal function, and tachyarrhythmias were compared before and sequentially at 6, 24, and 36 hours after the initiation of thyroxine administration. Long-term outcome was also defined. All patients had statistically significant improvements in cardiac index, pulmonary capillary wedge pressure, and mean arterial pressure at 24 and 36 hours post-initiation of thyroxine. No sustained tachyarrhythmias were seen during the thyroxine infusion. In 9 of 10 patients who underwent left ventricular assist device placement and/or heart transplantation, the use of thyroxine served as an effective adjunctive measure to allow transitioning to definitive surgical therapy. The 6-month and 1-year cohort survival rates, achieved by the transition to surgical therapy, were 90% and 80%, respectively. CONCLUSION: The beneficial hemodynamic properties of intravenous thyroid hormone can be effectively used in otherwise terminal situations of cardiogenic shock, and in such situations, the use of thyroid hormone can serve as a pharmacological adjunct to a definite surgical intervention. Further studies in larger numbers of patients might be warranted to confirm these findings.

Modulatory impact of cardiac rehabilitation on hyperhomocysteinemia in patients with coronary artery disease and "normal" lipid levels.

In coronary patients with "relatively normal" lipid values and hyperhomocystinemia (levels > or =15 micromol/L), significant 12% reductions in homocysteine levels occurred after cardiac rehabilitation and exercise training. This benefit from cardiac rehabilitation and exercise training may lead to 20% to 30% reductions in overall coronary artery disease risk.

Renin-angiotensin system: genes to bedside.

Atherosclerosis and its vascular sequela are responsible for considerable morbidity and mortality rates. Several risk factors have been implicated in the pathogenesis of atherosclerosis, and the search for other risk factors continues on the medical horizon. Renin-angiotensin system (RAS), a multienzyme, multilocale axis, has been extensively studied as an important mediator of atherosclerosis. Recently, the tissue-based angiotensin system has been suggested as the most significant pathway of RAS. A genetic polymorphism in the human gene for the angiotensin-converting enzyme (ACE), one of the two enzymes of RAS, has been found to have a strong association with higher risk for acute coronary events, sudden cardiac death, vascular restenosis after angioplasty, and idiopathic and hypertrophic cardiomyopathy. Clinical and animal data support angiotensin II to be the final common pathway in the enzyme cascade of RAS and ACE as the key enzyme in the generation of Angiotensin II. ACE gene polymorphism appears to modify expression of cellular and free ACE levels and could represent a genetic marker for cardiovascular disease.

Management of cardiac allograft vasculopathy by transmyocardial laser revascularization.

Transmyocardial laser revascularization provides a unique and effective intervention for symptomatic relief and improvement of myocardial perfusion in diffuse cardiac allograft vasculopathy.

Mechanisms of hypertension in cardiac transplantation and the role of cyclosporine.

The use of cyclosporine in solid organ transplantation has been shown to be associated with the development of hypertension and nephrotoxicity. Several mechanisms, including endothelin-mediated systemic vasoconstriction, impaired vasodilatation secondary to reduction in nitric oxide, and altered cytosolic calcium translocation, have been proposed to underlie cyclosporine-induced hypertension. In addition, other studies have shown activation of the sympathetic nervous system and the renin-angiotensin system, as well as abnormalities in prostaglandin metabolism, as culpable mechanisms. Hemodynamic features of cyclosporine-induced hypertension consist of elevated peripheral vascular resistance, ventricular vascular uncoupling contributing to left ventricular hypertrophy, and abnormalities in the diastolic function of the allograft. Combined calcium-channel blockers and angiotensin-converting enzyme inhibitors have been used for this treatment of this clinical problem, and they achieve blood pressure control in 65% of patients. Moreover, these agents may also be beneficial in preventing development of cardiac allograft vasculopathy, a long-term nemesis in cardiac transplantation.

Heparin-induced thrombocytopenia with thrombotic complications.

Heparin-induced thrombocytopenia with thrombotic complications is a serious clinical problem. The diagnosis is confirmed by a positive heparin-induced platelet aggregation test and/or detection of white clots upon pathological exam after a presumptive diagnosis based on these criteria: (1) Development of thrombocytopenia of less than 100,000 mm3 while receiving heparin therapy; (2) Normalization of the platelet count after an interruption in heparin therapy; (3) The presence of thrombotic complications; and (4) Exclusion of other causes of thrombocytopenia. Eight patients with heparin-induced thrombocytopenia were encountered at the Charleston Area Medical Center, Memorial Division, in a recent 20-month period. Various types of heparin, routes of administration, and indications were implicated. The mean platelet nadir was 25,750 mm3 and the mean time to onset of of heparin-induced thrombocytopenia was 4.9 days. Thrombotic complications included seven patients with arterial occlusions of the legs, six with deep-vein thrombosis of the legs (three had pulmonary embolism), and five with combined arterial and venous thrombosis. Treatment strategies included discontinuation of heparin in all patients; intravenous infusion of dextran in five patients, followed by arterial thrombectomy in three patients; urokinase therapy in two patients for arterial thrombotic complications; and insertion of Greenfield filters in four patients for venous thrombotic complications. All surviving patients were given warfarin. The mortality rate was 25 percent and the morbidity rate was 38 percent. In conclusion, an initial platelet count should be obtained on all patients prior to receiving heparin, followed by repeat platelet counts every two to three days. Once thrombocytopenia or thrombosis is diagnosed, heparin should be discontinued and other therapeutic modalities considered.

Management of malignant ventricular arrhythmias using antitachycardia devices.

Cardioverter defibrillators were implanted in 26 patients at Charleston Area Medical Center for management of cardiac arrest (7 patients), and drug refractory sustained ventricular tachycardia (19 patients). A variety of operative approaches and concomitant surgical procedures were utilized in the implantation of these devices. No operative deaths occurred. A superficial wound infection was the only operative complication. During the follow-up period (9.3 +/- 5 months), 11 of 26 patients (46 percent) had a defibrillator discharge and one death occurred (3 percent), which was due to heart failure. Patients with malignant ventricular arrhythmias may present with sustained monomorphic ventricular tachycardia with associated syncope, pre-syncope or without any associated symptoms. Unfortunately, cardiac arrest may be the initial presentation. The use of antitachycardia devices such as implantable cardioverter defibrillators and antitachycardia pacemakers has allowed physicians to more successfully treat patients with malignant ventricular arrhythmias. In a significant number of patients with these arrhythmias, such devices are now used as first-line therapy.

The effects of a minidose of heparin on peritonitis in rats.

Sprague-Dawley rats with peritonitis treated with either a subcutaneous or intraperitoneal minidose of heparin show a significant increase in survival time when compared with controls. In the treatment groups, adhesions and abscesses were less severe and localized to the area of gangrenous bowel. Heparin also significantly reduced the incidence of recovery of viable bacteria from the blood and peritoneal cavity. These findings may be related to a decreased deposition of fibrinogen within the abdomen or to the early mobilization of fibrin.